PMID- 9968167 TI - Spin formalism in the algebraic scattering theory for heavy ions. PMID- 9968168 TI - Microscopic coupled-channels analysis of 9Be(p,p') for 100 <= Ep <= 500 MeV. PMID- 9968169 TI - Multifractals at relativistic energies. PMID- 9968170 TI - Target dependence of central rapidity Lambda production in sulfur-nucleus collisions at 200 GeV/c per nucleon. PMID- 9968171 TI - Nuclear equation of state with momentum-dependent interactions. PMID- 9968172 TI - Transverse energy and forward energy production in a high energy nuclear collision model. PMID- 9968173 TI - Quark distributions in nuclei. PMID- 9968174 TI - Effect of multiple scattering on the measurement of nuclear transparency. PMID- 9968175 TI - Parity nonconservation for neutron resonances in 238U. PMID- 9968176 TI - Parity nonconservation for neutron resonances in 232Th. PMID- 9968178 TI - Spin, moments, and mean square nuclear charge radius of 77Sr. PMID- 9968177 TI - Relativity and the enhancement of the weak axial-charge matrix elements in the lead region. PMID- 9968179 TI - Hypernuclear currents in a relativistic mean-field theory with tensor omega YY couplings. PMID- 9968180 TI - Fragment-formation positions in proton-induced collisions. PMID- 9968181 TI - Probe dependence of the quasielastic peak. PMID- 9968182 TI - Nucleus-nucleus potential in the range -2 Lambda -bar Lambda process. PMID- 9968345 TI - Pion absorption in tritium at intermediate energies. PMID- 9968346 TI - Relativistic effects in proton-proton bremsstrahlung. PMID- 9968347 TI - Chiral symmetry and the nucleon-nucleon interaction: Tensor decomposition of Feynman diagrams. PMID- 9968348 TI - Three-boson system with absorptive short range potential. PMID- 9968350 TI - Unsuitability of 157Tb for light-neutrino rest-mass studies. PMID- 9968349 TI - Magnetic moments and shape coexistence in the light Br isotopes. PMID- 9968351 TI - Cross sections for formation of metastable states of 79Br, 90Zr, and 95Tc nuclei at 14 MeV neutron energy. PMID- 9968352 TI - Gamow-Teller strength in A=37 nuclei. PMID- 9968353 TI - T=13 double isobaric analog state in 138Ce via pion-induced double charge exchange. PMID- 9968355 TI - 18O(3He,p)20F reaction. PMID- 9968354 TI - 1,2,3H, 4He emission from 96Ru nuclei (E* PMID- 9968357 TI - Projected quasiparticle calculations on the heavy odd-mass N=82 isotones. PMID- 9968356 TI - Average resonance capture study of 126Te. PMID- 9968359 TI - Analysis of the compressibility of a finite symmetrical nucleus in terms of a simple, analytically tractable model. PMID- 9968358 TI - Nuclear equation of state in the MIT bag crystal model for nuclear matter. PMID- 9968360 TI - Structure of the low-lying intrinsic states in 156Eu. PMID- 9968361 TI - Thermal properties of zinc isotopes in the static path approximation. PMID- 9968362 TI - Exploring the validity of Z=38 and Z=50 proton closed shells in even-even Mo isotopes. PMID- 9968363 TI - Kinetic-energy operator in the effective shell-model interaction. PMID- 9968364 TI - Multipole response of 11Li. PMID- 9968365 TI - alpha -d resonances and the low-lying states of 6Li. PMID- 9968367 TI - Pair transfer and the sub-barrier fusion of 18O+58Ni. PMID- 9968366 TI - Three- and five-nucleon transfers in 9Be(p, alpha )6Li reaction at 25 and 30 MeV. PMID- 9968368 TI - Electric and magnetic dipole transitions from broad s-wave neutron resonance in even-even sd-shell nuclei. PMID- 9968369 TI - Low energy optical model studies of proton scattering on 54Fe and 56Fe. PMID- 9968370 TI - Critical study of source size extractions from p-p correlations in 20Ne reactions at 30 MeV/nucleon. PMID- 9968371 TI - Gauge invariance and the nonrelativistic Ward-Takahashi identity. PMID- 9968372 TI - Temperature-dependent relativistic microscopic optical potential of a nucleon. PMID- 9968373 TI - Absorption contribution to the pion double-charge-exchange reaction. PMID- 9968374 TI - Pion absorption on polarized nuclear targets. PMID- 9968375 TI - Spin observables at threshold for meson photoproduction. PMID- 9968376 TI - Electromagnetic and pion-nuclear reactions on 15N. PMID- 9968377 TI - Meson exchange current contribution to K+-nucleus scattering. PMID- 9968379 TI - Gamma emission in precompound reactions. II. Numerical application. PMID- 9968378 TI - Gamma emission in precompound reactions. I. Statistical model and collective gamma decay. PMID- 9968380 TI - Production of Delta ++(1232) in carbon-carbon collisions at 4.2 GeV/c per nucleon. PMID- 9968381 TI - Measurements of nu W2 and R= sigma L/ sigma T from inelastic electron-aluminum scattering near x=1. PMID- 9968382 TI - Antihyperon-hyperon production in the meson exchange framework. PMID- 9968383 TI - Ward-Takahashi identities for the radiative axial-vector vertex and low-energy theorem for the pion electroproduction. PMID- 9968384 TI - Quasiparticle properties of the quarks of the Nambu-Jona-Lasinio model. PMID- 9968385 TI - Sum rule description of color transparency. PMID- 9968386 TI - Muon-neutrino carbon charged-current interaction near the muon threshold. PMID- 9968388 TI - Doorway state approximation and sign correlations in parity nonconservation in compound neutron resonances. PMID- 9968387 TI - Covariant description of the Delta in nuclear matter. PMID- 9968389 TI - Atomic parity nonconservation: Electroweak parameters and nuclear structure. PMID- 9968390 TI - Sign correlations in parity-violating compound-nucleus reactions. PMID- 9968391 TI - "Shadow" model for sub-barrier fusion applied to light systems: Determination of the reaction rate. PMID- 9968392 TI - New nuclei near the proton drip line around Z=40. PMID- 9968393 TI - Search for the double beta decay of 244Pu. PMID- 9968394 TI - Search for the I pi =1(-) state in 218Ra. PMID- 9968395 TI - Realistic estimate of incomplete fusion excitation function in nucleus-nucleus collisions. PMID- 9968396 TI - Quadrupole contribution to two-neutron removal in heavy ion collisions. PMID- 9968397 TI - Momentum distributions in reactions with radioactive beams. PMID- 9968398 TI - Riemann's theorem for quantum tilted rotors. PMID- 9968400 TI - Evidence for new isomers and band structures in 80Rb. PMID- 9968399 TI - Erratum: Decay of 120Ba PMID- 9968401 TI - Double beta decays of 100Mo to excited states in 100Ru. PMID- 9968402 TI - Double blocking in the superdeformed 192Tl nucleus. PMID- 9968403 TI - Resolution of nuclear ground and isomeric states by a Penning trap mass spectrometer. PMID- 9968404 TI - Mass asymmetry, equation of state, and nuclear multifragmentation. PMID- 9968405 TI - Towards a microscopic understanding of nuclear structure functions. PMID- 9968406 TI - Effective summation over intermediate states in double-beta decay. PMID- 9968408 TI - Measurement of the cross-section ratio 3H(d, gamma )5He/3H(d, alpha )n at 100 keV. PMID- 9968407 TI - pi ++d-->p+p below 21 MeV. PMID- 9968409 TI - Differential cross section for n-p elastic scattering in the angular region 50 degrees< theta *<180 degrees at 459 MeV. PMID- 9968410 TI - Internal bremsstrahlung: Exact relativistic independent-particle-approximation calculations. PMID- 9968411 TI - Three-body approach to NN-->N Delta reaction. PMID- 9968412 TI - One-pion-exchange potential with self-energy. PMID- 9968413 TI - Search for population of superdeformed states in 194Pb using 194Bi beta + decay. PMID- 9968414 TI - High spin states in 93Tc. PMID- 9968415 TI - 223Ra levels fed in the 223Fr beta decay. PMID- 9968416 TI - He-vector3(e-vectore') quasielastic asymmetry. PMID- 9968417 TI - Nuclear structure of 178Lu. PMID- 9968418 TI - Pion double charge exchange on nickel isotopes and generalized seniority. PMID- 9968419 TI - Short lifetimes in 28Si. PMID- 9968421 TI - Gamow-Teller beta-decay rates for A <= 18 nuclei. PMID- 9968420 TI - Level lifetime measurements and the structure of neutron-rich 78Ge. PMID- 9968422 TI - Core polarization effect on the discrete proton hole states of 205Tl. PMID- 9968423 TI - Negative parity states and octupole collectivity of even Ge isotopes. PMID- 9968424 TI - Calculation of the moment of inertia by a proper treatment of pairing correlations. PMID- 9968426 TI - Collective modes in hot and dense nuclear matter. PMID- 9968427 TI - 12C( alpha, gamma )16O E2 cross section in a microscopic four-alpha model. PMID- 9968425 TI - Influence of bulk properties on the surface structure of finite nuclei. PMID- 9968428 TI - Interaction of stopped antiprotons with copper. PMID- 9968430 TI - Neutral pion production in the 16O+27Al reaction at 94 MeV/nucleon. PMID- 9968429 TI - N* electroproduction and propagation in nuclei. PMID- 9968432 TI - Bromine and iodine excitation-function measurements with protons and deuterons at 3-17 MeV. PMID- 9968431 TI - Neutron total cross sections at intermediate energies. PMID- 9968433 TI - Comparison of the quasifree charge-exchange reaction for 12C and 54Fe. PMID- 9968434 TI - Cross sections for A=6-30 fragments from the 4He+28Si reaction at 117 and 198 MeV. PMID- 9968436 TI - Coulomb polarizability of the deuteron and the E1 capture mechanism in the 4He(d, gamma )6Li reaction. PMID- 9968435 TI - Semiclassical particle-rotor model of one-neutron transfer reactions. PMID- 9968437 TI - Global Dirac phenomenology for proton-nucleus elastic scattering. PMID- 9968438 TI - Radiative strength in the compound nucleus 157Gd. PMID- 9968439 TI - First-principles calculation of the cross sections for nuclear excitation by electron capture of channeled nuclei. PMID- 9968441 TI - Intermittent behavior of nuclear multifragments. PMID- 9968440 TI - Resonant characteristics of statistical fluctuations in 12C+12C reaction cross sections. PMID- 9968443 TI - Lifetime of (e+e-) puzzle's composite particle: No valid limits yet. PMID- 9968442 TI - Mechanism of disintegration of emulsion nuclei by relativistic light nuclei. PMID- 9968444 TI - Isospin splitting in the baryon octet and decuplet. PMID- 9968445 TI - Sign correlations and the mechanism for parity violation. PMID- 9968446 TI - Perturbative treatment of parity nonconservation in neutron-nucleus scattering within the optical model. PMID- 9968448 TI - Level lifetimes in N=82 isotones from Doppler-shift attenuation method mixed target measurements. PMID- 9968447 TI - Cross section for the primordial reaction 8Li(p,n)8Be (g.s.) at Ec.m.=1.5 MeV. PMID- 9968450 TI - Nilsson-based truncation of the nuclear shell model. PMID- 9968449 TI - Vector analyzing power iT11 in the pi +d-->pp reaction in the energy region T pi =350-450 MeV. PMID- 9968451 TI - Effects of prefission neutron emission on the fission fragment angular distributions in heavy-ion-induced fission. PMID- 9968452 TI - Explanation of recent observations of very large electromagnetic dissociation cross sections. PMID- 9968453 TI - Entropy and fractal characteristics of multiparticle production at relativistic heavy ion interactions. PMID- 9968454 TI - Comment on "Fragmentation of gold projectiles with energies of 200-980 MeV/nucleon. I. Experimental method, charge yields, and transverse momenta" PMID- 9968455 TI - Reply to "Comment on 'Fragmentation of gold projectiles with energies of 200-980 MeV/nucleon. I. Experimental method, charge yields, and transverse momenta' " PMID- 9968456 TI - Rotational structure and signature inversion in odd-odd 84Y. PMID- 9968457 TI - First evidence for states in Hg nuclei with deformations between normal and super deformation. PMID- 9968458 TI - Microscopic approach to pion-nucleus dynamics. PMID- 9968459 TI - Comparison between proton capture on 13N and Coulomb breakup of 14O. PMID- 9968460 TI - K+ production far below the free nucleon-nucleon threshold in heavy-ion collisions. PMID- 9968461 TI - Measurement of the reaction 3He( gamma,pp)n and its relation to three-body forces. PMID- 9968462 TI - Breakup energy spectrum of singlet deuterons measured using d+d-->d*+d* four-body reaction at 15.7 MeV. PMID- 9968463 TI - Deuteron quadrupole moment and 3S1-3D1 state properties. PMID- 9968464 TI - Variational Monte Carlo calculations of 3H and 4He with a relativistic Hamiltonian. PMID- 9968465 TI - Skyrmions and the nuclear force. PMID- 9968466 TI - Pion-nucleon coupling constant. PMID- 9968468 TI - Nuclear matter compressibility from isoscalar giant monopole resonance. PMID- 9968467 TI - Decay of the 02+ state in 80Kr. PMID- 9968469 TI - Reconstructive correction of aberrations in nuclear particle spectrographs. PMID- 9968470 TI - Band structure in the neutron-rich lanthanide nucleus 152Nd. II. Allowed and K forbidden transitions from the negative-parity bands. PMID- 9968471 TI - Three-quasiparticle states analysis in odd-mass lead isotopes. PMID- 9968472 TI - Instabilities against exotic cluster decays in "stable" nuclei with Z and N in the neighborhood of spherical and deformed closed shells. PMID- 9968473 TI - Nuclear deformation in the mass-80 and mass-100 regions. PMID- 9968474 TI - Exact one-loop vacuum polarization effects in (1+1)-dimensional quantum hydrodynamics. PMID- 9968475 TI - Particle-hole state densities with good isospin. PMID- 9968476 TI - Apparent quadratic deformation scaling of transition strengths in samarium isotopes. PMID- 9968477 TI - Lipkin-Nogami method at finite temperature in the static-path approximation. PMID- 9968478 TI - Approximate seniority-dictated boson-quasifermion mapping and derivation of the interacting boson fermion model. PMID- 9968479 TI - Spin-isospin SU(4) symmetry in sd- and fp-shell nuclei. PMID- 9968480 TI - Systematics of isospin character of transitions to the 21+ and 31- states in 90,92,94,96Zr. PMID- 9968481 TI - (d,2He) reactions at Ed=260 MeV as a possible probe to nuclear spin-isospin excitation. PMID- 9968482 TI - 16O( gamma,p0)15N cross section from 33 to 69 MeV. PMID- 9968483 TI - Fragmentation of polarized 23Na on 208Pb and the random-walk model. PMID- 9968485 TI - Correlation symmetries in sequential three-body final state reactions. PMID- 9968484 TI - Elastic scattering of 318 MeV 6Li from 12C and 28Si: Unique phenomenological and folding-model potentials. PMID- 9968486 TI - Systematics of the double isobaric analog state cross section at 50 MeV. PMID- 9968487 TI - Measuring dynamical fluctuations in relativistic heavy ion collisions. PMID- 9968488 TI - Unitary, relativistic resonance model for pi N scattering. PMID- 9968489 TI - Computational comparison of quantum-mechanical models for multistep direct reactions. PMID- 9968490 TI - alpha -16O and alpha -15N optical potentials in the range between 0 and 150 MeV. PMID- 9968491 TI - Massive neutrinos and right-handed weak currents in double beta decay. PMID- 9968492 TI - Comparison of potential models with the pp scattering data below 350 MeV. PMID- 9968493 TI - Resonant state expansion of the resolvent. PMID- 9968494 TI - Pion correlations for 1.2A GeV lanthanum on lanthanum. PMID- 9968495 TI - Transport model with quasipions. PMID- 9968497 TI - In-medium behavior of the QCD theta term and the value of CP violation in nuclei. PMID- 9968496 TI - Distortion of two-pion interferometry by multipion correlations. PMID- 9968498 TI - Precise determination of relative and absolute beta beta -decay rates of 128Te and 130Te. PMID- 9968500 TI - Induced pseudoscalar axial current in polarized nuclear beta decay. PMID- 9968499 TI - Parity-violating quasielastic electron scattering. PMID- 9968502 TI - Polarization transfer in 12C(p PMID- 9968501 TI - Reaction mechanism of 7Li(3He,p)9Be and 7Li(3H,n)9Be and primordial nucleosynthesis of 9Be. PMID- 9968503 TI - Total cross sections for the A( pi +, pi + pi -) reaction at T pi +=280 MeV. PMID- 9968504 TI - Gamow-Teller matrix elements for two-neutrino double beta decay within a second quasi-random-phase approximation. PMID- 9968505 TI - Multipole character of the proposed 220 eV transition in 229Pa. PMID- 9968506 TI - Parity-violating muon and heavy lepton scattering in the 12C-->12C* nuclear transition. PMID- 9968507 TI - Temperature and density effects on the one-pion exchange potential. PMID- 9968508 TI - Theoretical energy distributions around threshold from coherent pion production. PMID- 9968509 TI - NpNn scheme and the saturation of collectivity in the A PMID- 9968510 TI - Effect of charge dependence of the nucleon-nucleon interaction on the properties of nuclear and neutron matter. PMID- 9968512 TI - Normalization for the random phase approximation with energy-dependent interactions. PMID- 9968511 TI - Disappearance of rotation in heavy-ion collisions. PMID- 9968513 TI - Comment on "Dynamical polarization potential due to the excitation of collective states" PMID- 9968514 TI - Reply to "Comment on 'Dynamical polarization potential due to the excitation of collective states' " PMID- 9968515 TI - Reply to "Comment on 'Resonant and nonresonant contributions to the photoactivation of 111Cd' " PMID- 9968516 TI - Erratum: Correlation between E2 and M1 transition strength in even-even vibrational, transitional, and deformed nuclei PMID- 9968517 TI - Extraction of the multifragmentation time scale in intermediate energy heavy-ion reactions. PMID- 9968518 TI - Application of a large-volume NaI scintillator to search for dark matter. PMID- 9968519 TI - Two-deuteron correlation functions in 14N+27Al collisions at E/A=75 MeV. PMID- 9968520 TI - Superdeformed band in 142Sm. PMID- 9968521 TI - Reconciling deformation parameters from fusion with those from Coulomb excitation. PMID- 9968522 TI - Highly deformed band in 136Pm and the anomalous dynamical moment of inertia behavior in the A~135 superdeformed region. PMID- 9968523 TI - On color transparency experiments. PMID- 9968524 TI - Extraction of total cross section data for the pi -p--> pi + pi -n reaction. PMID- 9968526 TI - Natural orbital representation in nuclei. PMID- 9968525 TI - Charge exchange effects in elastic scattering with radioactive beams. PMID- 9968527 TI - Pion interaction with the trinucleon up to the eta production threshold. PMID- 9968528 TI - Inclusive pi d breakup reactions. PMID- 9968529 TI - Anatomy of the soft photon approximation in hadron-hadron bremsstrahlung. PMID- 9968531 TI - Resonances in Lambda d scattering and the Sigma hypertriton. PMID- 9968530 TI - Nucleon-nucleon pion-exchange tested in three-body reactions. PMID- 9968532 TI - Spectroscopy of 123I. PMID- 9968533 TI - Absolute B(E1) values in the shape transitional 148-152Sm isotopes. PMID- 9968534 TI - Stretched two-nucleon configurations in 210Pb. PMID- 9968535 TI - Level densities of 28Al, 29Si, and 41Ca inferred from fluctuation measurements. PMID- 9968536 TI - Gamma-ray multipole mixing ratios in 71Ge. PMID- 9968538 TI - Pion double charge exchange on 56Fe at T pi =400 MeV. PMID- 9968537 TI - 5(-) "octupole" states in 146,148Nd and 148Sm via proton scattering. PMID- 9968539 TI - Particle-vibration coupling in a basis with resonant states. PMID- 9968540 TI - Thermal and quantal fluctuations in the pairing plus quadrupole model. PMID- 9968541 TI - Proton impurity in the neutron matter: A nuclear polaron problem. PMID- 9968542 TI - Hierarchical trapping of resonance states at high level density. PMID- 9968543 TI - Relativistic extended Thomas-Fermi calculations of finite nuclei with realistic nucleon-nucleon interactions. PMID- 9968544 TI - High energy gamma rays from 252Cf spontaneous fission. PMID- 9968545 TI - Isospin effects in the photodisintegration of light nuclei. PMID- 9968546 TI - 16O+Ag/Br interactions at 2.1 GeV/nucleon and some aspects of intermittency. PMID- 9968547 TI - Study of 206Pb by means of the 209Bi(p PMID- 9968548 TI - 58Ni+n transmission, differential elastic scattering, and capture measurements and analysis up to 813 keV. PMID- 9968549 TI - Peripheral interactions in the collision of 16O+238U at 110.4 MeV bombarding energy. PMID- 9968550 TI - Measurement of branching ratios of low energy deuteron-induced nuclear reactions on 2H, 6Li, and 10B. PMID- 9968551 TI - Energy dependence of two-nucleon pion absorption on 16O. PMID- 9968553 TI - High energy gamma rays from 14N+natAg at 35 MeV/nucleon. PMID- 9968552 TI - High-lying resonances observed in heavy-ion transfer reactions. PMID- 9968554 TI - Double charge exchange in 93Nb( pi +, pi -)93Tc at T pi =164, 230, and 294 MeV. PMID- 9968556 TI - Relativistic cluster dynamics of nucleons and mesons. I. Kinematics and covariance. PMID- 9968555 TI - Total reaction and partial cross section calculations in proton-nucleus (Zt <= 26) and nucleus-nucleus reactions (Zp and Zt <= 26). PMID- 9968557 TI - "Shadow" properties in sub-barrier fusion. PMID- 9968558 TI - Recoil effects in sequential emission and Coulomb dissociation. PMID- 9968559 TI - Scaling algorithm to calculate heavy-ion spallation cross sections. PMID- 9968561 TI - Quadrupole amplitude in the gamma N Delta transition. PMID- 9968560 TI - Strong-interaction effect measurements in sigma hyperonic atoms of W and Pb. PMID- 9968562 TI - Solving momentum-space integral equations for quarkonium spectra with confining potentials. III. Bethe-Salpeter equation with spin. PMID- 9968563 TI - New N=84 isotone: 136Te. PMID- 9968565 TI - Hyperdeformation in 152Dy at very high spins. PMID- 9968564 TI - X-ray yields of superdeformed states in 193Hg. PMID- 9968566 TI - Fusion resonance in 5He, 5Li. PMID- 9968567 TI - Diffuse well analysis of exotic decay of heavy nuclei. PMID- 9968568 TI - Experimental evidence against a model incorporating fission before K equilibration. PMID- 9968569 TI - Determination of extra-push energies for fusion from differential fission cross section measurements. PMID- 9968571 TI - 11Li+p elastic scatterings in a four-body model with the eikonal approximation. PMID- 9968570 TI - Distorted-wave analysis of proton scattering from 6Li near the alpha -d breakup threshold. PMID- 9968572 TI - Reaction simulations as a guide to lifetime information from particle-particle correlations. PMID- 9968573 TI - Uncertainty in K+-nucleus total cross section analysis. PMID- 9968574 TI - Erratum: Rise and fall of multifragment emission at relativistic energy PMID- 9968575 TI - Neutron alignment at the first crossing in 78Kr. PMID- 9968576 TI - Behavior of the Be and C total photonuclear cross section in the nucleon resonance region. PMID- 9968577 TI - Rotation-induced transition from superfluid to normal phase in mesoscopic systems: 168Yb and adjacent nuclei. PMID- 9968578 TI - Collective band in 193Hg with Ex >= 5.7 MeV. PMID- 9968579 TI - Phenomenology of flow disappearance in intermediate-energy heavy ion collisions. PMID- 9968580 TI - Near-threshold production of eta mesons. PMID- 9968582 TI - Coplanar and noncoplanar pp bremsstrahlung. PMID- 9968581 TI - Forward angle analyzing power in p PMID- 9968583 TI - Simulating the Langevin force by simple noise in nuclear one-body dynamics. PMID- 9968584 TI - Neutron-deuteron scattering calculations with the Paris potential using the W matrix representation of the two-body input. PMID- 9968585 TI - Evidence for superdeformed shape isomeric states in 28Si at excitations above 40 MeV through observations of selective particle decays of 16O+12C resonances in 8Be and alpha channels. PMID- 9968586 TI - High spin structure in odd-proton nuclei 129,131Pr. PMID- 9968587 TI - Statistical gamma decay of the giant dipole resonance in highly excited 46Ti and 52Cr. PMID- 9968588 TI - alpha -decay properties of neutron-deficient polonium and radon nuclei. PMID- 9968589 TI - Beta-delayed proton decay of 25Si. PMID- 9968590 TI - Half-life of 32Si. PMID- 9968591 TI - Double giant resonances in pion double charge exchange on 51V, 115In, and 197Au. PMID- 9968593 TI - Pionic decay of Lambda hypernuclei. PMID- 9968592 TI - Deformation dependence of low lying M1 strengths in even Nd isotopes. PMID- 9968594 TI - Z=64 subshell gap in the shell model and the effective boson number in the interacting boson model. PMID- 9968595 TI - Spins of proton capture resonances in 26Al and 30P from their gamma-ray spectra. PMID- 9968596 TI - Density of discrete levels in 116Sn. PMID- 9968598 TI - Thermal properties of nuclear matter with a momentum-dependent effective interaction. PMID- 9968597 TI - Systematic study of neutron-deficient Ho isotopes in a relativistic mean field theory. PMID- 9968599 TI - E1 transitions from octupole vibration states. PMID- 9968600 TI - Relativistic nuclear matter with self-consistent correlation energy. PMID- 9968601 TI - Role of collectivity in the structure of 120,122,124Sb nuclei. PMID- 9968602 TI - Even-odd anomalous tunneling effect. PMID- 9968603 TI - Isotopic yields of intermediate-mass fragments emitted in E/A=50 MeV 4He+116,124Sn reactions. PMID- 9968604 TI - Search for Gamow-Teller strength in the continuum via the 3He(n,p)3H reaction at 288 MeV. PMID- 9968605 TI - Spin determination of valence and inner hole states via the 208Pb(d PMID- 9968606 TI - Symmetric mass-division process in nuclei with mass numbers around ACN=100. PMID- 9968607 TI - Confirmation of the reported 330-keV electron line in e++Th interactions using the positron emitter 82Sr. PMID- 9968608 TI - Measurements of transverse electron scattering from the deuteron in the threshold region at high momentum transfers. PMID- 9968609 TI - Effective interaction for 16O(p,p') and 40Ca(p,p') at Ep=200 MeV. PMID- 9968610 TI - Evolution of the reaction dynamics in the interaction of copper with 15-90 MeV/nucleon 12C ions. PMID- 9968611 TI - Double differential cross sections for neutron emission induced by 256 MeV and 800 MeV protons. PMID- 9968613 TI - Role of neutron flow in the enhancement of heavy ion fusion at energies below the Coulomb barrier and the systematics of threshold barriers. PMID- 9968612 TI - Two-pion correlations and multiplicity effects in La on La collisions. PMID- 9968615 TI - Medium effects on kaon and antikaon spectra in heavy-ion collisions. PMID- 9968614 TI - Interference effect of doorway states in a radiative capture reaction. PMID- 9968616 TI - Study of a strongly damped collision between heavy ions. PMID- 9968618 TI - Analysis of total neutron-nucleus cross sections using relativistic impulse approximation. PMID- 9968617 TI - Multipair transfer in collisions between heavy nuclei. PMID- 9968620 TI - Studying the 16O+12C dynamic polarization potential by inversion. PMID- 9968619 TI - Inclusive (p, Delta ++) and (p,p' pi + reactions. PMID- 9968621 TI - Inclusive measurements of electromagnetic dissociation of 197Au targets. PMID- 9968623 TI - Radiative corrections to the nucleon axial vector coupling constant in the chiral soliton quark model. PMID- 9968622 TI - Relativistic hydrodynamics in a global fashion. PMID- 9968624 TI - Effective action for SU(N) at a finite temperature. PMID- 9968625 TI - Becchi-Rouet-Stora-Tyutin treatment of a simplified baryon model. PMID- 9968626 TI - Chiral color-dielectric model with perturbative quantum pions and gluons. PMID- 9968627 TI - Shell model level structure in 215At. PMID- 9968628 TI - Electron capture and beta + decay of 147Tm. PMID- 9968629 TI - Quark antisymmetrization effects in nonidentical hadron systems. PMID- 9968630 TI - Pion contributions to the electromagnetic interaction with a nucleus. PMID- 9968631 TI - Comment on "Spectroscopy of samarium isotopes in the sdg interacting boson model" PMID- 9968632 TI - Erratum: Spin assignments of angular momentum mismatched resonances in the 16O+16O system PMID- 9968634 TI - Comparison of one- and two-proton transfer in 32S+92,98,100Mo, 93Nb at energies near the Coulomb barrier. PMID- 9968633 TI - Collective oblate bands in 196Pb. PMID- 9968635 TI - Hexadecapole interacting boson approximation structure functions in neodymium isotopes. PMID- 9968637 TI - Antiproton production from heavy ion collisions at 14.6 GeV/c. PMID- 9968638 TI - Charge independence and charge symmetry breaking interactions and the Coulomb energy anomaly in isobaric analog states. PMID- 9968636 TI - Antiproton production in p+A collisions at 14.6 GeV/c. PMID- 9968639 TI - Quasielastic scattering of 11Li using realistic three-body wave functions. PMID- 9968640 TI - Phase-shift analysis of NN scattering below 160 MeV: Indication for a strong tensor force. PMID- 9968641 TI - Effective interaction of three resonantly interacting particles and the force range. PMID- 9968642 TI - Variational two- and three-particle solutions of the relativistic Yukawa model. PMID- 9968644 TI - Completeness relations and resonant state expansions. PMID- 9968643 TI - 3S1-3D1 effective-range parameters of some realistic nucleon-nucleon potentials. PMID- 9968645 TI - Transfer results for odd-odd 196Au and the extended supersymmetry. PMID- 9968647 TI - Proton spectroscopy beyond the drip line near A=150. PMID- 9968646 TI - Yrast isomers in exotic N=81 nucleus 151Yb studied using a fragment mass analyzer. PMID- 9968648 TI - Search for the K pi =1(+) two-proton band in 166Er. PMID- 9968649 TI - Accurate Mossbauer line-shape measurements including interference in 182W, 183W, 191Ir, and 159Tb. PMID- 9968650 TI - Fission of heavy hypernuclei formed in antiproton annihilation. PMID- 9968651 TI - Interpretation of Lambda -attachment probabilities in hyperonic fission. PMID- 9968652 TI - Effects due to temperature-dependent nuclear binding energies on the equation of state for hot nuclear matter. PMID- 9968653 TI - New S pair. PMID- 9968654 TI - Signature effects in some N=90 odd-Z rare-earth nuclei. PMID- 9968655 TI - Coulomb instability of hot nuclei in quantum hadrodynamics. PMID- 9968656 TI - Electric-dipole transitions and octupole softness in odd-A rare-earth nuclei. PMID- 9968657 TI - One and two broken pairs in the interacting boson model: High-spin states in 190,192,194Hg. PMID- 9968658 TI - Quasielastic 40Ca(e,e'p) cross sections in a many-particle self-consistent Hartree model. PMID- 9968659 TI - New island of cluster emitters. PMID- 9968660 TI - Beta-delayed proton decay of 65Se. PMID- 9968661 TI - Angular momentum distributions for 16O+144Nd. PMID- 9968662 TI - Equilibrium and preequilibrium emission in some alpha -induced reactions on enriched isotopes 128,130Te at moderate excitation energies. PMID- 9968663 TI - Proton-induced nucleon knockout from polarized 3He at 220 MeV. PMID- 9968665 TI - Asymmetric fission of 47V induced by the 23Na+24Mg reaction. PMID- 9968664 TI - Theoretical treatment of analog (p,n) cross sections for odd nuclei: Application to measurements of 105Pd at 26 MeV. PMID- 9968666 TI - Transverse momentum correlations between particle-particle pairs as a probe of effective emitter mass: 40Ar+natAg (E/A=7, 17, 27, and 34 MeV). PMID- 9968668 TI - Global properties of proton-hole strengths in mass 54 to 70 nuclei. PMID- 9968667 TI - 36Cl(n,p)36S cross section from 25 meV to 800 keV and the nucleosynthesis of the rare isotope 36S. PMID- 9968669 TI - 10B(p,n)10C reaction at 186 MeV. PMID- 9968670 TI - Thermal characteristics of composite systems formed in fusion of 28Si with 118Sn and 124Sn nuclei. PMID- 9968671 TI - Neutron transition densities from 88Sr(p,p') at Ep=200 MeV. PMID- 9968673 TI - Spectroscopy of 238,239Pu studied by quasielastic reactions. PMID- 9968674 TI - Neutron propagation in 12C for energies 20 to 45 MeV. PMID- 9968672 TI - Polarization transfer in quasifree ( p PMID- 9968676 TI - Wigner-Thomas spin precession in polarized coincidence electronuclear scattering. PMID- 9968675 TI - Analyzing powers for 9Be(6Li PMID- 9968677 TI - Stochastic nucleation: Percolation without a lattice. PMID- 9968678 TI - Left-right asymmetry in p-barp--> pi - pi + PMID- 9968679 TI - Evidence for a nuclear halo from 11Li elastic scattering measured at 637 MeV incident energy on a 12C target. PMID- 9968681 TI - Consistent dynamical and statistical description of fission of hot nuclei. PMID- 9968680 TI - Scattering of GeV electrons by light nuclei. PMID- 9968682 TI - Pauli blocking effects for nucleon-nucleus scattering. PMID- 9968683 TI - Isospin effects in elastic proton-nucleus scattering. PMID- 9968684 TI - Transverse response functions in the Delta -resonance region. PMID- 9968685 TI - Feshbach-Kerman-Koonin analysis of 93Nb reactions: P-->Q transitions and reduced importance of multistep compound emission. PMID- 9968686 TI - Self-similarity and scaling behavior in nuclear collision. PMID- 9968688 TI - Strangeness production in proton and heavy ion collisions at 200A GeV. PMID- 9968687 TI - Electromagnetic production of Higgs bosons, supersymmetric particles, glueballs, and mesons in ultrarelativistic heavy-ion collisions. PMID- 9968689 TI - Impact-parameter dependence of the electromagnetic particle production in ultrarelativistic heavy-ion collisions. PMID- 9968690 TI - Correlation measurements in high-multiplicity events. PMID- 9968691 TI - Color conductivity and evolution of the minijet plasma. PMID- 9968692 TI - Finite nuclei in relativistic models with a light chiral scalar meson. PMID- 9968693 TI - Pion electroproduction at threshold. PMID- 9968694 TI - Coupled-channel dynamics in the Nambu-Jona-Lasinio model. PMID- 9968695 TI - CP-odd nucleon potential. PMID- 9968696 TI - Reaction rate for destruction of 7Li and primordial nucleosynthesis. PMID- 9968697 TI - Energy dependence of fusion evaporation-residue cross sections in the 28Si+12C reaction. PMID- 9968698 TI - Lack of evidence for a superdeformed band in 192Pb. PMID- 9968699 TI - Multifragment disintegration of 238U at 1A GeV. PMID- 9968701 TI - Spectroscopic factors for alpha -cluster wave functions in 44Ti observed via the (6Li,d) reaction. PMID- 9968700 TI - Search for an M0 transition in 170Yb. PMID- 9968702 TI - Folding model using a bare elementary interaction for 12C+12C elastic scattering. PMID- 9968703 TI - Macroscopic models for the fusion of very heavy ions. PMID- 9968704 TI - Real part of the polarization potential for 11Li-induced fusion reactions. PMID- 9968706 TI - Strong absorption approximation for the elastic scattering of 800 MeV/c pions from nuclei. PMID- 9968705 TI - Deformed Gaussian orthogonal ensemble description of isospin mixing and spectral fluctuation properties. PMID- 9968707 TI - Electromagnetic properties of 181Ir: Evidence of beta stretching? PMID- 9968708 TI - Use of summation methods in the calculation of nuclear double beta decay processes. PMID- 9968709 TI - Nucleon-nucleon bound state contribution to the proton scattering by nuclei. PMID- 9968711 TI - Atomic masses near 146Gd: Evidence for a systematic deviation between experiment and mass formulas. PMID- 9968710 TI - Comment on "Pairing correlations studied in the two-level model" PMID- 9968712 TI - Erratum: Determination of the level density of 29Si from Ericson fluctuations PMID- 9968713 TI - Sub-barrier one- and two-neutron pickup measurements in 32S+93Nb, 98,100Mo reactions at 180 degrees. PMID- 9968714 TI - Prescission neutron emission from 104Pd. PMID- 9968716 TI - Effect of isospin on three nucleon pion absorption in light nuclei. PMID- 9968715 TI - Large radial flow in nucleus-nucleus collisions. PMID- 9968717 TI - Negative-parity inversion doublet alpha -cluster band in 18O. PMID- 9968718 TI - Exotic nuclei in a relativistic mean-field approach. PMID- 9968719 TI - Significance of inclusive electron-nucleus cross sections ratios in the multi-GeV region. PMID- 9968720 TI - Quasifree pion production in the three-nucleon system. PMID- 9968721 TI - Crossing-symmetric two-particle reduction of four-point vertex. PMID- 9968723 TI - One-loop corrections to threshold gamma p-->p pi 0 production in the linear sigma model. PMID- 9968722 TI - Ghost poles in the nucleon propagator: Vertex corrections and form factors. PMID- 9968724 TI - Beta decay of 31,32Na and 31Mg: Study of the N=20 shell closure. PMID- 9968725 TI - Proton capture resonance spins by multidimensional scaling: fp nuclei. PMID- 9968726 TI - Excitations of 144Sm in (p,p'). PMID- 9968727 TI - Ground-state magnetization density of 89Y. PMID- 9968728 TI - Nuclear structure of odd-odd 82Y. PMID- 9968729 TI - Energy of the 4(()+) isomer and new bands in the odd-odd nucleus 74Br. PMID- 9968730 TI - Search for an eta bound state in pion double charge exchange on 18O. PMID- 9968731 TI - High spin shell model states in the isotope 4390Tc47. PMID- 9968732 TI - Evidence for single particle structure of high spin states in 144Pm and 145Pm. PMID- 9968734 TI - Orbital M1 versus E2 strength in deformed nuclei: A new energy weighted sum rule. PMID- 9968733 TI - beta + decay and cosmic-ray half-life of 91Nb. PMID- 9968735 TI - Pairing Hamiltonian by a path integral Monte Carlo procedure. PMID- 9968736 TI - Role of the rho -meson coupling constant in relativistic mean field studies. PMID- 9968737 TI - K dependence in the gamma decay of neutron resonances in 168Er and 178Hf. PMID- 9968739 TI - Comparison of the pn quasiparticle RPA and shell model for Gamow-Teller beta and double-beta decays. PMID- 9968738 TI - Relativistic hydrodynamics with quantum hadrodynamics equation of state. PMID- 9968740 TI - Momentum distribution of fragments in heavy-ion reactions: Dependence on the stochastic collision process. PMID- 9968741 TI - Relativistic ring-diagram nuclear matter calculations. PMID- 9968742 TI - Alpha decay of 16O excited states. PMID- 9968743 TI - Search for a bound state of a negative pion and neutrons in 18O+Be collisions. PMID- 9968744 TI - Proton-90Zr mean field between -60 and +185 MeV from a dispersive optical model analysis. PMID- 9968747 TI - Multiplicity dependence of azimuthal distributions for 36Ar+197Au collisions at E/A=35 MeV. PMID- 9968745 TI - Probing alpha -particle wave functions using (d PMID- 9968746 TI - Possible signatures of nuclear-molecular formation in O+C systems. PMID- 9968748 TI - Neutron transfer reactions at large distances. PMID- 9968749 TI - Gamma width of 14O*(5.17 MeV) and the stellar 13N(p, gamma )14O reaction rate. PMID- 9968750 TI - High-spin stretched states excited in (n,p) reactions at 300 MeV. PMID- 9968751 TI - Resonance photodecay amplitudes to 1.8 GeV. PMID- 9968752 TI - Intranuclear cascade-percolation approach for protons and light fragments production in neon-niobium reactions at 400 and 800 MeV per nucleon. PMID- 9968753 TI - Viscosity and the equation of state in high energy heavy-ion reactions. PMID- 9968754 TI - Pion production: Where's the coherence? PMID- 9968755 TI - Comparison of WKB and exact penetrabilities through two-peaked fission barriers. PMID- 9968757 TI - Effective interaction for inelastic proton scattering based on the relativistic impulse approximation. PMID- 9968756 TI - Effective number of protons for quasifree ( pi -, pi 0) at 500 and 400 MeV. PMID- 9968758 TI - Algebraic and coordinate space potentials from heavy ion scattering. PMID- 9968759 TI - Diabolic effects on nuclear rotational state population in two-neutron transfer. PMID- 9968760 TI - Measurement of dielectron production in niobium-niobium collisions at 1.05 GeV/nucleon. PMID- 9968761 TI - Collective effects on transport coefficients of relativistic nuclear matter. PMID- 9968763 TI - Fluctuating hadronic cross sections and transverse energy distributions in nucleus-nucleus collisions. PMID- 9968762 TI - Photon emission from hot hadronic matter described by an effective chiral Lagrangian. PMID- 9968764 TI - QCD sum rules for nucleons in nuclear matter II. PMID- 9968765 TI - Response of nonrelativistic confined systems. PMID- 9968767 TI - No evidence of the 17-keV neutrino in the decay of 71Ge. PMID- 9968768 TI - Relativistic and nuclear structure effects in parity-violating quasielastic electron scattering. PMID- 9968766 TI - Electron-capture decay of 100Tc and the double- beta decay of 100Mo. PMID- 9968769 TI - 6He beta decay to the alpha +d channel in a three-body model. PMID- 9968770 TI - Decay properties of exotic N PMID- 9968771 TI - Beta decay of 187Re and cosmochronology. PMID- 9968772 TI - Implications of the recent 59Co(n,p)59Fe experiment for stellar electron capture rates. PMID- 9968773 TI - Sub-barrier fusion of 16O+144Nd. PMID- 9968775 TI - Shapes of exotic nuclei in the mass A=70 region. PMID- 9968774 TI - Total disintegration of Ag and Br nuclei by 4.5A GeV/c silicon nuclei. PMID- 9968776 TI - p-barp--> Xi -bar Xi reaction in the meson exchange picture. PMID- 9968777 TI - Nuclear density of states for moving fused compound systems. PMID- 9968778 TI - Predictions for p PMID- 9968779 TI - 3He scattering from 6Li: A semimicroscopic approach. PMID- 9968780 TI - Nonunitary nature of the Dyson boson mapping revisited. PMID- 9968781 TI - Comment on "Energy partition in near-barrier strongly damped collisions 58Ni+208Pb" PMID- 9968783 TI - Comment on "Pion-nucleus scattering around the (3,3) resonance" PMID- 9968782 TI - Reply to "Comment on 'Energy partition in near-barrier strongly damped reaction 58Ni+208Pb' " PMID- 9968784 TI - Erratum: "Perturbative treatment of parity nonconservation in neutron-nucleus scattering within the optical potential" PMID- 9968785 TI - Neutron decay of 10Li produced by fragmentation. PMID- 9968786 TI - New oblate band in 196Hg with quenched M1 strength. PMID- 9968787 TI - Perturbed alignments within an i13/2 neutron intruder band in 141Gd. PMID- 9968788 TI - Geochemical estimation of the half-life for the double beta decay of 96Zr. PMID- 9968790 TI - Momentum dependence of the rho - omega mixing amplitude in a hadronic model. PMID- 9968789 TI - Fragment emission time scale in intermediate energy heavy ion collisions. PMID- 9968791 TI - Resonance properties in nuclear matter. PMID- 9968792 TI - Effect of breakup reactions on the fusion of a halo nucleus. PMID- 9968793 TI - Dressing two nucleons at the same time. PMID- 9968794 TI - Inelastic electron scattering from the three-nucleon bound states with polarization. PMID- 9968795 TI - Separable expansions of the NN t matrix via exact half-off-the-energy-shell methods. PMID- 9968796 TI - Natural orbital representation and short-range correlations in nuclei. PMID- 9968797 TI - Helium-ion-induced fission excitation functions of terbium and ytterbium. PMID- 9968798 TI - 40Ca(p,d)39Ca reaction at 65 MeV. PMID- 9968799 TI - One neutron photoemission cross section of 238U. PMID- 9968800 TI - Neutron-capture gamma-ray study of levels in 135Ba and description of nuclear levels in the interacting-boson-fermion model. PMID- 9968802 TI - Electron conversion coefficients in 127Ba and 130La. PMID- 9968801 TI - Electromagnetic excitation of 11Li. PMID- 9968803 TI - Calibration of the transient field for Pt ions in gadolinium and magnetic moments of the 21+ states in 196,198Pt. PMID- 9968805 TI - Thermodynamical properties of relativistic nuclear matter with derivative scalar coupling. PMID- 9968804 TI - Cluster-phonon model applied to the 91Zr nucleus. PMID- 9968806 TI - Quark condensate at finite baryon density. PMID- 9968807 TI - Neutron halo of 6He in a microscopic model. PMID- 9968808 TI - Longitudinal response functions of heavier nuclei. PMID- 9968809 TI - Quantum theory of large amplitude collective motion and the Born-Oppenheimer method. PMID- 9968811 TI - Analytic expressions for the Lambda energy in the lower nodeless Lambda single particle states. PMID- 9968810 TI - Relativistic mean field description of the even-even proton drip line nuclei near Z=34. PMID- 9968813 TI - Angular distribution in alpha-induced fission of 232Th and 238U. PMID- 9968812 TI - 27Al(d,3He)26Mg reaction at 29 MeV. PMID- 9968814 TI - Symmetric and asymmetric ternary fission of hot nuclei. PMID- 9968815 TI - Deep spallation of medium mass isotopes by protons. PMID- 9968816 TI - Total nuclear reaction probability of 270 to 390 (1)4N ions in Si and CsI. PMID- 9968817 TI - Low-energy pion scattering to 1(-) states in 12C. PMID- 9968818 TI - np-elastic analyzing power AN0 and spin transfer KNN. PMID- 9968819 TI - Mass and charge distributions of Cl-induced heavy-ion reactions. PMID- 9968820 TI - Analyzing powers for elastic and inelastic scattering of polarized 6Li from 9Be at 32 MeV. PMID- 9968821 TI - Impact parameter dependence of preequilibrium particle emission. PMID- 9968823 TI - Rotational state populations in 16O+154Sm near-barrier fusion. PMID- 9968822 TI - Systematics of 8Li-induced radioactive beam reactions: E=13-20 MeV. PMID- 9968824 TI - Momentum distributions for (11Li, 9Li+n+n) breakup reactions. PMID- 9968826 TI - rho -meson effective mass and electron scattering in medium nuclei. PMID- 9968825 TI - Nucleon polarization in deuteron electrodisintegration. PMID- 9968828 TI - Nuclear response in delta-isobar region in the (3He,t) reaction. PMID- 9968827 TI - Binding effects in proton-nucleus elastic scattering. PMID- 9968830 TI - Relativistic corrections and unitary equivalence in elastic electron deuteron scattering. PMID- 9968829 TI - Sequential contribution to nonanalog pion double charge exchange in the Delta 33 resonance region. PMID- 9968831 TI - Global model of transverse energy and multiplicity distributions in ultrarelativistic nuclear collisions. PMID- 9968833 TI - Exclusive process 2H(e,e'p)N* as a tool for investigation of the quark structure of the deuteron. PMID- 9968832 TI - Supercooling and final-state effects on dilepton spectra. PMID- 9968834 TI - Coulomb effect in operator expansion method for two-neutrino double beta decay. PMID- 9968835 TI - Nambu-Jona-Lasinio models beyond the mean-field approximation. PMID- 9968836 TI - Null tests of time-reversal invariance. PMID- 9968838 TI - Half-life of the 21+ state of 94Zr. PMID- 9968837 TI - Study of the beta-delayed alpha-particle emission of 16N. PMID- 9968839 TI - Identification of the s1/2 145Dy ground state. PMID- 9968840 TI - 14N(n,p)14C cross section near thermal energy. PMID- 9968841 TI - Radiative capture of polarized deuterons on 7Li. PMID- 9968842 TI - Observation of 146Er electron capture and beta + decay. PMID- 9968843 TI - Improved microscopic calculation of initial exciton number. PMID- 9968844 TI - Nucleus-nucleus reaction cross section at low energies: Modified Glauber model. PMID- 9968845 TI - Gauge-invariant projection method for the pion photoproduction and electroproduction amplitudes. PMID- 9968846 TI - Deep inelastic collision followed by disassembly in the reaction 136Xe+209Bi at Elab/A=28.2 MeV. PMID- 9968848 TI - Energy dependence of massive-fragment multiplicity. PMID- 9968847 TI - Simple model for deriving sdg interacting boson model Hamiltonians: 150Nd example. PMID- 9968849 TI - Qualitative behavior of halo nuclei elastic scattering angular distributions. PMID- 9968850 TI - Relativistic calculations of the superheavy nucleus 298114. PMID- 9968851 TI - Does the pi NN coupling "constant" vary with energy? PMID- 9968853 TI - Comment on "Shadow model for sub-barrier fusion applied to light systems" PMID- 9968852 TI - Ground state properties of the exotic Ba isotopes. PMID- 9968854 TI - New evidence against 17-keV neutrino emission in the beta decay momentum spectrum of 35S. PMID- 9968855 TI - Measurement of the magnetic form factor of the neutron. PMID- 9968856 TI - Relation of collective observables to nuclear shapes. PMID- 9968857 TI - Critical test of multi-j supersymmetries from magnetic moment measurements. PMID- 9968859 TI - Band structure systematics and symmetries in even-even nuclei. PMID- 9968858 TI - Meson-exchange and nonlocality effects in proton-antiproton annihilation into two pseudoscalar mesons. PMID- 9968860 TI - NN core interactions and differential cross sections from one gluon exchange. PMID- 9968861 TI - Neutron resonance parameters and thermal-neutron capture by 43Ca. PMID- 9968862 TI - g factor of the 3/2(+) 93.6 keV level in 91Sr. PMID- 9968864 TI - Possible detection of the double beta +/electron-capture decay. PMID- 9968863 TI - Band crossing observed in neutron-rich Pd isotopes via spontaneous fission of 252Cf. PMID- 9968865 TI - Isotopic variation of the rms charge radii of Ca isotopes. PMID- 9968866 TI - g-matrix calculations in finite hypernuclei. PMID- 9968867 TI - Realistic level densities in fragment emission at high excitation energies. PMID- 9968868 TI - Quantum-deformation algebra studied as an analytical equivalent of the s,d interacting boson model: Energy spectra. PMID- 9968869 TI - Delta -excited nuclear matter in the derivative scalar coupling model. PMID- 9968870 TI - Relation between the phenomenological interactions of the algebraic cluster model and the effective two-nucleon forces. PMID- 9968871 TI - Towards model independent single-particle wave functions. PMID- 9968872 TI - Quantum molecular dynamics simulation of multifragment production in heavy ion collisions at E/A=600 MeV. PMID- 9968873 TI - Li-Li azimuthal angular correlations: A test for emission from a rotating source versus instantaneous multifragmentation. PMID- 9968874 TI - Target fragments from the interaction of 93Nb and 181Ta with 47 MeV/nucleon 12C ions. PMID- 9968875 TI - Breakup of the projectile in 16O-induced reactions on 27Al, 58Ni, and 197Au targets around 100 MeV/nucleon. PMID- 9968876 TI - Search for abnormal-nucleus production in heavy-ion collisions. PMID- 9968877 TI - Complete and incomplete momentum transfer components in the natSi(16O,X) reaction at 96.4, 112.4, and 127.8 MeV. PMID- 9968878 TI - Absolute pp-elastic cross sections from 492 to 793 MeV. PMID- 9968879 TI - Emission temperatures from widely separated states in 14N- and 129Xe-induced reactions. PMID- 9968880 TI - New determination of the asymptotic D-state to S-state ratio of the triton using (d PMID- 9968881 TI - 16O breakup in quasielastic reactions near the Fermi energy. PMID- 9968882 TI - Energy dependence of multipole strength distributions in the 32S(n,p)32P reaction. PMID- 9968883 TI - Transition from complete to incomplete fusion in asymmetric heavy ion reactions. PMID- 9968884 TI - Transverse form factors of 117Sn. PMID- 9968886 TI - Pion absorption mechanism for very light nuclei. PMID- 9968885 TI - Coincident proton emission induced by 200 MeV protons on 197Au. PMID- 9968887 TI - Determination of proton strange form factors from nu p elastic scattering. PMID- 9968889 TI - Medium-energy hadron-nucleus scattering in the 1/N expansion formalism. PMID- 9968890 TI - Double-folding model potential for 6Li scattering with 4He: Absence of anomalous reduction factor. PMID- 9968888 TI - Geometric model for nuclear absorption from microscopic theory. AB - A parameter-free geometric model for nuclear absorption is derived from microscopic theory. The expression for the absorption cross section in the eikonal approximation taken in integral form is separated into a geometric contribution, described by an energy-dependent effective radius, and two surface terms which are shown to cancel in an asymptotic series expansion. For collisions of light nuclei, an expression for the effective radius is derived using harmonic-oscillator nuclear density functions. A direct extension to heavy nuclei with Woods-Saxon densities is made by identifying the equivalent half density radius for the harmonic-oscillator functions. Coulomb corrections are incorporated and a simplified geometric form of the Bradt-Peters type obtained. Results spanning the energy range of 1 MeV/nucleon to 1 GeV/nucleon are presented. Good agreement with experimental results are obtained. PMID- 9968892 TI - Exclusive quasifree pion photoproduction on complex nuclei in the Delta region. PMID- 9968891 TI - Partial-wave analysis of all nucleon-nucleon scattering data below 350 MeV. PMID- 9968893 TI - Eikonal expansion for total cross sections of heavy ion reactions. PMID- 9968894 TI - One- and two-electron atomic screening in fusion reactions. PMID- 9968895 TI - High-energy pion-nucleus elastic scattering. PMID- 9968897 TI - Refinements of the nucleon-exchange transport model for the emission of hard photons and nucleons. PMID- 9968896 TI - Study of the total reaction cross section via the reaction dynamical model. PMID- 9968899 TI - Shadowing and antishadowing of the photon structure function of the hydrogen molecule. PMID- 9968898 TI - Interactions of ultrarelativistic oxygen nuclei in emulsion. PMID- 9968900 TI - Relativistic mean-field calculations of Lambda and Sigma hypernuclei. PMID- 9968901 TI - Effects of negative energy components in the constituent quark model. PMID- 9968902 TI - Effects of boundary on momentum distribution of quarks in a quark-gluon plasma. PMID- 9968904 TI - K pi =3(+) band at 1862 keV in 178Hf. PMID- 9968903 TI - Model analysis of time-reversal symmetry test in the 57Fe gamma -transition experiment. PMID- 9968905 TI - Excitation energies of two J pi =1(-) states in 18O. PMID- 9968907 TI - One-pion exchange potential and pi N form factors in the Skyrme model. PMID- 9968906 TI - Probing hadronic structure with the decay Delta -->Nl+l- PMID- 9968908 TI - Spin-orbit and spin-spin interactions in Lambda N and NN scattering. PMID- 9968910 TI - Radius and radial moments of the deuteron. PMID- 9968909 TI - Universal characteristics of transverse momentum transfer in intermediate energy heavy ion collisions. AB - A microscopic optical model formalism for estimating momentum transfer in intermediate energy heavy ion collisions predicts universal behavior of the transverse component. In particular, for symmetric systems (Ap = AT) heavier than niobium, it appears that values of P perpendicular/A are independent of the mass and charge of the colliding nuclei and vary only with impact parameter and incident beam energy. This suggests that momentum transfer per nucleon saturates to some limiting value with increasing mass. PMID- 9968911 TI - Formation and decay of toroidal and bubble nuclei and the nuclear equation of state. PMID- 9968912 TI - Beta decay of 44V. PMID- 9968913 TI - Coherent states description of alpha decay. PMID- 9968914 TI - Short range correlations and fractional occupation probabilities. PMID- 9968915 TI - Pion absorption in 4He above the delta resonance. PMID- 9968916 TI - Deformed intruder band in 113I. PMID- 9968917 TI - Lifetimes of the decay from superdeformed to normal deformed in 135Nd. PMID- 9968918 TI - Time scales for spinodal decomposition in nuclear matter with pseudoparticle models. PMID- 9968919 TI - Full three-body calculation for d PMID- 9968920 TI - Dark sphere with a bright interior: A nucleus viewed by intermediate energy alpha particles. PMID- 9968921 TI - Nuclear mass dependence of chaotic dynamics in the Ginocchio model. PMID- 9968922 TI - Widths of transverse momentum distributions in intermediate-energy heavy-ion collisions. AB - The need to include dynamical collision momentum transfer contributions, arising from interacting nuclear and Coulomb fields, to estimates of fragment momentum distributions is discussed. Methods based upon an optical potential model are presented. Comparisons with recent experimental data of the Siegen group for variances of transverse momentum distributions for gold nuclei at 980 A MeV fragmenting on silver foil and plastic nuclear track detector targets are made. The agreement between theory and experiment is good. PMID- 9968924 TI - Proposed new experimental case to investigate the weak parity nonconserving couplings in 20F. PMID- 9968923 TI - Factorial moments and multifractal analysis at relativistic energies. PMID- 9968926 TI - Criterion for the applicability of standard thermodynamics in heavy ion collisions. PMID- 9968925 TI - Medium effects on the rho meson. PMID- 9968927 TI - Structure of neutron deficient Sn isotopes. PMID- 9968928 TI - pi pi -angular correlations for pi -p--> pi + pi -n in the region of the Delta dominance. PMID- 9968930 TI - Lifetimes and electromagnetic decay properties of negative-parity states in 150,152,154Sm from (n,n' gamma ) measurements. PMID- 9968929 TI - Comment on the question of reflection asymmetry in 229Pa. PMID- 9968931 TI - Study of excited states in 85Kr and 86Kr: Evidence for neutron-core excitations in the N=50 nucleus 86Kr. PMID- 9968932 TI - Transition strengths in 79Rb. PMID- 9968933 TI - Extended quasiparticle approximation and Brueckner theory. PMID- 9968934 TI - Systematics of triaxial deformation in Xe, Ba, and Ce nuclei. PMID- 9968935 TI - Semiempirical determination of effective p-n monopole matrix elements. PMID- 9968937 TI - Self-consistent relativistic calculation of nucleon mean free path. PMID- 9968936 TI - Hot and dense asymmetric nuclear matter. PMID- 9968939 TI - Isovector nuclear response in carbon. PMID- 9968938 TI - Problem of parity nonconservation in 57Fe and 119Sn nuclei. PMID- 9968940 TI - Microscopic calculations of the spectra of light nuclei. PMID- 9968941 TI - Studies of intermediate-mass fragment emission in the 3He+natAg, 197Au reactions between 0.48 and 3.6 GeV. PMID- 9968942 TI - Separation of Delta S=0 and Delta S=1 in the response of 12C to 318 MeV protons. PMID- 9968943 TI - Experimental limit on parity violation in nonresonant neutron-nucleus scattering. PMID- 9968944 TI - Neutron capture and total cross sections of 144Sm. PMID- 9968945 TI - Isospin symmetry in nuclear transitions from pion scattering. PMID- 9968946 TI - Elastic scattering of 58Ni+27Al at near-barrier energies. PMID- 9968947 TI - Elastic scattering of 28Si from 27Al at 70, 80, 90, and 100 MeV. PMID- 9968948 TI - Dipole and spin-dipole resonances in charge-exchange reactions on 12C. PMID- 9968950 TI - Resonance structures through time-dependent potentials. PMID- 9968949 TI - Quantum theoretical approach to meson production in nuclear media via Cherenkov mechanisms. PMID- 9968951 TI - Dynamic response function and large-amplitude dissipative collective motion. PMID- 9968952 TI - Distorted-wave calculation of the (p,p' pi +) reaction. PMID- 9968953 TI - Mean fields: Explicit dispersive and retardation properties of the dynamical polarization potential within a simple model. PMID- 9968956 TI - Electrodisintegration of polarized deuterons. PMID- 9968955 TI - Inclusive quasielastic neutrino reactions in 12C and 16O at intermediate energies. PMID- 9968954 TI - Entropy production in the Au+Au reaction between 150A and 800A MeV. PMID- 9968957 TI - Importance of higher order coupling effects in sub-barrier fusion. PMID- 9968959 TI - Electromagnetic dissociation of nuclei in heavy-ion collisions. PMID- 9968958 TI - Parton equilibration in relativistic heavy ion collisions. PMID- 9968960 TI - Muon-induced fission: A probe for nuclear dissipation and fission dynamics. PMID- 9968961 TI - Deuteron breakup effects in transfer reactions using a Weinberg state expansion method. PMID- 9968962 TI - Kinematically accessible vector meson resonance enhancements in p(K-,e+e-) Lambda, Sigma 0, Lambda (1405). PMID- 9968963 TI - Statistical properties and stability of hot nuclei in a semiclassical relativistic approach. PMID- 9968964 TI - Magnetic interaction between relativistic atomic electrons and parity nonconserving nuclear moments. PMID- 9968966 TI - Nuclear and hypernuclear particle-hole states in the relativistic sigma - omega mean field theory: Nuclear matter formalism. PMID- 9968965 TI - History of quark-gluon plasma evolution from photon interferometry. PMID- 9968967 TI - Role of K Delta interactions in K+N pion production. PMID- 9968968 TI - Color magnetic corrections to quark model valence distributions. PMID- 9968969 TI - Search for anomalies in low-energy electron scattering from thorium. PMID- 9968970 TI - Atomic parity nonconservation and neutron radii in cesium isotopes. PMID- 9968971 TI - Neutron capture in 148,150Sm: A sensitive probe of the s-process neutron density. PMID- 9968972 TI - Alpha scattering and capture reactions in the A=7 system at low energies. PMID- 9968974 TI - Isoscalar M1 strength in lead. PMID- 9968973 TI - Pion double charge exchange on 16O at T pi =300-500 MeV. PMID- 9968975 TI - 1266-keV gamma branch in 31Si decay. PMID- 9968977 TI - Nuclear deexcitations of nucleon holes associated with nucleon decays in nuclei. PMID- 9968976 TI - Role of nuclear structure in the spin-isospin nuclear response problem. PMID- 9968979 TI - Effects of pairing correlation in light nuclei. PMID- 9968978 TI - Effect of channel coupling on spin distribution at and above Coulomb barrier energies. PMID- 9968980 TI - General behavior of double beta decay amplitudes in the quasiparticle random phase approximation. PMID- 9968981 TI - Nature of the 20Na 2646-keV level and the stellar reaction rate for 19Ne(p, gamma )20Na. PMID- 9968982 TI - Test of generalized seniority with pion double charge exchange on the nickel isotopes. PMID- 9968983 TI - Description of alpha clustering including continuum configurations. PMID- 9968984 TI - Relation between neutron and proton deformation lengths. PMID- 9968985 TI - Comment on "Search for the I pi =1(-) state in 218Ra" PMID- 9968987 TI - Gamow-Teller beta decay and isospin impurity in nuclei near the proton drip line. PMID- 9968988 TI - e-p off-shell cross section in quasielastic (e,e'p) reactions. PMID- 9968986 TI - Velocity correlations of intermediate mass fragments produced in central collisions of Au+Au at E=150A MeV. PMID- 9968990 TI - Electromagnetic scattering from relativistic bound states. PMID- 9968989 TI - Nuclear effects in deep inelastic scattering of polarized electrons off polarized 3He and the neutron spin structure functions. PMID- 9968991 TI - Spin assignments for the ground states of 155Lu and 157Lu. PMID- 9968992 TI - Compton scattering from the proton. PMID- 9968993 TI - Unitarity cusp in proton Compton scattering. PMID- 9968994 TI - Monte Carlo evaluation of path integrals for the nuclear shell model. PMID- 9968995 TI - Pion double-charge-exchange operator. PMID- 9968996 TI - Off-shell behavior of the pi - eta mixing amplitude. PMID- 9968997 TI - Pion absorption on 3He. II. Antisymmetrization and angular decomposition of the Faddeev-based amplitude. PMID- 9968998 TI - f7/2 proton alignment in 49Cr. PMID- 9968999 TI - Level structure of the odd mass Pr isotopes. III. Levels of 147Pr88 populated in the beta decay of 56-s 147Ce. PMID- 9969000 TI - Observation of pion-related effects in the photofission of preactinide nuclei. PMID- 9969001 TI - Neutron resonance spectroscopy of 113In and 115In. PMID- 9969002 TI - High spin states of 91Mo and 89Nb. PMID- 9969003 TI - Seniority v=5 states in 4189Nb48. PMID- 9969004 TI - Level structure of 89Mo. PMID- 9969005 TI - High resolution 162 MeV pion scattering to 6(-) stretched states in 26Mg. PMID- 9969006 TI - Band crossing in the odd-particle system. PMID- 9969007 TI - Neutron-skin and proton-skin formations in exotic nuclei far from stability. PMID- 9969008 TI - Simultaneous evaluation of the shell and pairing corrections to the nuclear deformation energy. PMID- 9969009 TI - Systematic variation of fission barrier heights for symmetric and asymmetric mass divisions. PMID- 9969010 TI - Shell-model calculations of Gamow-Teller strength in 51V, 54Fe, and 59Co. PMID- 9969012 TI - Nuclear structure study of the odd-A Tc isotopes within the neutron-proton interacting boson-fermion model. PMID- 9969011 TI - Approximate particle number projection for rotating nuclei. PMID- 9969013 TI - Microscopic calculation of in-medium nucleon-nucleon cross sections. PMID- 9969014 TI - Order parameter for pairing systems. PMID- 9969015 TI - Charge radius of the neutron: Discussion of the differences between experimental values. PMID- 9969016 TI - Algebraic 12C+12C cluster model of the 24Mg nucleus. PMID- 9969017 TI - Some general constraints on identical band symmetries. PMID- 9969018 TI - Octupole fragmentation and O(6) symmetry in even-A Pt isotopes. PMID- 9969019 TI - Spin-isospin strength and spectral functions. PMID- 9969020 TI - Effects of the single-particle potential insertions in the effective interaction. PMID- 9969021 TI - Configuration mixing in 56Co and 46Sc using (d PMID- 9969022 TI - Fast neutron scattering cross sections at small angles and optical model parameters. PMID- 9969023 TI - Photofissility of 232Th measured with tagged photons from 250 to 1200 MeV. PMID- 9969024 TI - Mass asymmetry dependence of scission times in the reactions of 18.5A MeV 136Xe+48Ti. PMID- 9969025 TI - Complete and incomplete fusion and emission of preequilibrium nucleons in the interaction of 12C with 197Au below 10 MeV/nucleon. PMID- 9969026 TI - Identification of a percolationlike critical region in the decay of excited calcium nuclei. PMID- 9969027 TI - Quasifree pion scattering at 500 MeV. PMID- 9969028 TI - Inclusive electron-nucleus scattering at high momentum transfer. PMID- 9969029 TI - Two-body disintegration of the deuteron with 0.8-1.8 GeV photons. PMID- 9969030 TI - Search for diabolical pair transfer in two-neutron transfer reactions. PMID- 9969031 TI - Absolute differential cross sections and charge asymmetries for pi +/-d elastic scattering at 30, 50, and 65 MeV. PMID- 9969032 TI - Spin correlation measurements for p-3He elastic scattering between 4.0 and 10.0 MeV. PMID- 9969033 TI - Effective range parametrization of phase shifts for p-3He elastic scattering between 0 and 12 MeV. PMID- 9969035 TI - Explanation of recent observations of very large electromagnetic dissociation cross sections. II. Higher order corrections. PMID- 9969034 TI - Mechanism of intermediate mass fragment emission at low energy. PMID- 9969036 TI - Role of strange quarks in quasielastic neutrino scattering. PMID- 9969038 TI - Pion scattering from spin 1/2 nuclei. PMID- 9969037 TI - Analysis of the reaction pi +d-->pp to 500 MeV. PMID- 9969039 TI - Gauge invariance and Compton scattering from relativistic composite systems. PMID- 9969040 TI - Phase shift analysis of pi +/--4He elastic scattering. PMID- 9969041 TI - Nuclear flow excitation function. PMID- 9969043 TI - Photon-hadron interactions in relativistic heavy ion collisions. PMID- 9969042 TI - Medium modification of meson propagation between two nucleons in finite nuclei. PMID- 9969044 TI - Electromagnetic dissociation of Pb nuclei in peripheral ultrarelativistic heavy ion collisions. PMID- 9969045 TI - Nuclear shadowing in a parton recombination model. PMID- 9969046 TI - Modified Skyrme model and the nucleon-nucleon interaction. PMID- 9969047 TI - Role of instantons in a chiral confining model. PMID- 9969048 TI - Study of the 13N(d,n)14O reaction cross section and its astrophysical implications for the 13N proton capture reaction. PMID- 9969049 TI - Interactions of 13.6-GeV/nucleon 16O and 28Si with carbon, aluminum, and copper. PMID- 9969050 TI - Neutron spectra from the 156Er compound nucleus populated by 12C- and 64Ni induced reactions. PMID- 9969051 TI - Intercalibration of 4He and 5Li nuclear thermometers for hot nuclei. PMID- 9969052 TI - Broken reflection symmetry in 114Xe. PMID- 9969053 TI - Directional correlation of gamma rays in 31 yr 178Hfm decay. PMID- 9969054 TI - Deuteron elastic scattering at 110 and 120 MeV. PMID- 9969055 TI - Excited states in neutron-deficient iridium nuclei populated in radioactive decays of 177-181Pt. PMID- 9969057 TI - Resonating group method in momentum space. PMID- 9969056 TI - Role of nuclear compressibility on the fission path. PMID- 9969058 TI - Analysis of the sign of E2/M1 multipole mixing ratio of transitions in the even Te isotopes. PMID- 9969060 TI - Nuclear shell effects at high temperatures. PMID- 9969059 TI - Relativistic three-particle scattering equations. PMID- 9969062 TI - alpha spectrum from 16N beta decay and the 12C( alpha, gamma )16O reaction. PMID- 9969061 TI - Specification of Kowalski-Noyes f ratios for coupled channels. PMID- 9969063 TI - Comment on "Evidence for superdeformed shape isomeric states in 28Si at excitations above 40 MeV through observations of selective particle decays of 16O+12C resonances in 8Be and alpha channels" PMID- 9969064 TI - Reply to "Comment on 'Evidence for superdeformed shape isomeric states in 28Si at excitations above 40 MeV through observations of selective particle decays of 16O+12C resonances in 8Be and alpha channels' " PMID- 9969065 TI - Measurement of the resonance at ER=1422 keV in 36Ar(p, gamma )37K. PMID- 9969066 TI - Momentum distributions for 12,14Be fragmentation. PMID- 9969067 TI - Effective fermion SO(6) dynamical symmetry in the platinum nuclei. PMID- 9969069 TI - Levinson's theorem for Dirac particles. PMID- 9969068 TI - Rotational behavior in intermediate energy heavy ion collisions. PMID- 9969070 TI - Deuteron form factors in the light-cone quantum mechanics "good" component approach. PMID- 9969071 TI - Coupled-channel potential for nucleons and deltas. PMID- 9969072 TI - Comparison of Born-Oppenheimer and hyperspherical adiabatic approximations in the trinucleon problem. PMID- 9969073 TI - Three-nucleon force and the Delta mechanism for pion production and pion absorption. PMID- 9969074 TI - From Skyrmions to NN phase shifts. PMID- 9969075 TI - Spin exchange between ion probes and localized moments in ferromagnets as the origin of transient fields. PMID- 9969076 TI - Intermediate structure in the photoexcitation of 77Sem, 79Brm, and 137Bam. PMID- 9969077 TI - Near yrast states in doubly odd 214Fr. PMID- 9969078 TI - Shape coexistence and signature splitting in 77Br. PMID- 9969079 TI - Spectroscopy of the superdeformed band in 196Pb. PMID- 9969080 TI - Coupling between rotational and vibrational motions with the cranking Bohr Mottelson Hamiltonian. PMID- 9969081 TI - Self-consistent description for x-ray, Auger electron, and nuclear excitation by electron transition processes. PMID- 9969083 TI - Virtual particles versus superconductive vacuum polarizations in interacting systems. PMID- 9969082 TI - Photodisintegration of 4He in the integrodifferential equation approach. PMID- 9969084 TI - 6p-2h core excitations in 20O. PMID- 9969085 TI - Boson-fermion mappings for odd systems from supercoherent states. PMID- 9969087 TI - Inclusive eta photoproduction in nuclei. PMID- 9969086 TI - Evaluation of angular integrals using matrix algebra: Applications to the alpha decay integrals Kll'm and the scattering of deformed nuclei. PMID- 9969088 TI - Light particle emission in the reaction 144Sm(32S, fission) at Elab=838 MeV. PMID- 9969090 TI - 2H(d, gamma )4He polarization observables at 20, 30, and 50 MeV. PMID- 9969089 TI - Impact-parameter dependence of neutral pion production in the 36Ar on 27Al collision at 95 MeV/nucleon. PMID- 9969091 TI - Direct and sequential contributions to the 26Mg(6Li PMID- 9969092 TI - 3He(n, gamma )4He cross section and the photodisintegration of 4He. PMID- 9969093 TI - Separated structure functions for the proton-knockout reaction 16O(e,e'p). PMID- 9969094 TI - Determination of the 6Li--> alpha +d vertex constant (asymptotic coefficient) from the 4He+d phase-shift analysis. PMID- 9969095 TI - Core polarization phenomena in pion-nucleus charge-exchange reactions above the delta resonance. PMID- 9969097 TI - Effective liquid drop description for the exotic decay of nuclei. PMID- 9969096 TI - General formula for the coalescence model. PMID- 9969098 TI - In-medium cross section and disappearance of flow. PMID- 9969099 TI - Uniform semiclassical and quantum calculations of Regge pole positions and residues for complex optical nuclear heavy-ion potentials. PMID- 9969100 TI - Dynamical evolution of hadronic matter in relativistic collisions. PMID- 9969101 TI - Relativistic microscopic description of proton-nucleus scattering at intermediate energies. PMID- 9969102 TI - Evidence for short-range correlations from high Q2 (e,e') reactions. PMID- 9969104 TI - Non-Abelian bremsstrahlung in a quark-gluon plasma. PMID- 9969103 TI - Thermal phenomenology of hadrons from 200A GeV S+S collisions. PMID- 9969105 TI - Dynamical effects of quantum chromodynamics on the surface tension of a cold strange quark nugget. PMID- 9969107 TI - Inertial parameters of the Skyrmion-Skyrmion system with the product ansatz. PMID- 9969106 TI - Deuteron photodisintegration, quark-gluon string model, and Regge phenomenology. PMID- 9969108 TI - Direct measurement of the 4He( gamma,p0) absolute cross section. PMID- 9969109 TI - Evidence for the statistical and sequential nature of 16O breakup into four alphas. PMID- 9969111 TI - Revealing intermittency in nuclear multifragmentation with 4 pi detectors. PMID- 9969110 TI - Coulomb excitation of the K pi =8(-) isomer in 178Hf. PMID- 9969112 TI - Three-quasiparticle excitations in 77Br. PMID- 9969113 TI - Approximate ways to treat the nucleon-nucleon tensor force in the four-nucleon bound state. PMID- 9969114 TI - Asymmetry versus symmetric quadrupole deformation in even-even nuclei with 94 <= A <= 192. PMID- 9969115 TI - Momentum fluctuations in the fragmentation of neutron-rich nuclei. PMID- 9969116 TI - Meson-exchange-currents contribution to axial charge transitions. PMID- 9969117 TI - Erratum: Pion-nucleus scattering at 800 MeV/c PMID- 9969118 TI - Lifetime of the 31- state and octupole collectivity in 96Zr. PMID- 9969119 TI - Lifetime measurements in the regular Delta I=1 oblate band in 197Pb. PMID- 9969120 TI - Spectroscopy of 186Pb with mass identification. PMID- 9969121 TI - Light fragment production in the 3.65A GeV 12C+208Pb reaction. PMID- 9969122 TI - Blocking effect in the 16(+)-->16(+) (p,t) transition on the isomeric 178Hfm2 target. PMID- 9969123 TI - Isomeric proton emission from the drip-line nucleus 156Ta. PMID- 9969125 TI - Deformation, pairing, and moments of inertia in ground-state bands of even-even rare-earth nuclei. PMID- 9969124 TI - Fission decay of very light nuclear systems. PMID- 9969126 TI - The quasifree (p PMID- 9969127 TI - Particle-drip lines from the Hartree-Fock-Bogoliubov theory with Skyrme interaction. PMID- 9969128 TI - d sigma /dEt in heavy ion collisions and nucleon-nucleon cross section fluctuations. PMID- 9969129 TI - Momentum and coordinate space three-nucleon potentials. PMID- 9969130 TI - Hypertriton calculation with meson-theoretical nucleon-nucleon and hyperon nucleon interactions. PMID- 9969131 TI - Nucleon polarization and cross section in photodisintegration of aligned and polarized deuterons at low and medium energies. PMID- 9969132 TI - Beta-delayed proton decay of 73Sr. PMID- 9969133 TI - Study of beta + and electron capture decay of 76Sr in gamma - gamma coincidence measurements. PMID- 9969134 TI - Search for high-lying octupole states and octupole fragmentation in 196Pt with the (n,n' gamma ) reaction. PMID- 9969135 TI - Collectivity in light zirconium isotopes: Evolution with neutron number and angular momentum. PMID- 9969137 TI - Precise widths of the 3089 and 3684 keV levels in 13C. PMID- 9969136 TI - Measurements of 10Be and 26Al production cross sections with 12 GeV protons by accelerator mass spectrometry. PMID- 9969138 TI - gamma spectroscopy of 117I: Three structural features. PMID- 9969139 TI - Measurements of magnetic moments in 150Sm. PMID- 9969140 TI - In-beam gamma -ray spectroscopy of 40Cl. PMID- 9969141 TI - Signatures for mixed-symmetry states in the U(5) limit of the neutron-proton interacting boson model. PMID- 9969142 TI - Relativistic Hartree-Fock approximation in a nonlinear model for nuclear matter and finite nuclei. PMID- 9969143 TI - 0 nu beta beta decays and shell model wave functions of 76Ge and 82Se. PMID- 9969144 TI - Shape transitions in 148Sm. PMID- 9969145 TI - Ground-state energy of a hard-sphere Fermi fluid. II. Spin and isospin. PMID- 9969146 TI - Quantum hadrodynamics parametrization: A least-squares fit to nuclear ground state properties. PMID- 9969147 TI - Momentum-dependent mean field based upon the Dirac-Brueckner approach for nuclear matter. PMID- 9969148 TI - Nucleon polarization in three-body models of polarized 6Li. PMID- 9969149 TI - Spectroscopic factors in 40Ca and 208Pb from (e,e'p): Fully relativistic analysis. PMID- 9969151 TI - Microscopic three-cluster study of 21-nucleon systems. PMID- 9969150 TI - Finite nuclear systems in a relativistic extended Thomas-Fermi approach with density-dependent coupling parameters. PMID- 9969152 TI - Multidetector study of primary projectilelike fragments in the reaction 40Ca+natCu at 35 MeV/nucleon. PMID- 9969153 TI - Near-threshold proton-induced neutral pion production from 12C. PMID- 9969154 TI - Scaling of the multiplicity in hadron-nucleus interactions. PMID- 9969155 TI - Proton single-particle states in 21,23Na through the (d,n) reaction. PMID- 9969156 TI - Multifragment events in the reaction 58Ni+27Al at 15.8 MeV/nucleon. PMID- 9969157 TI - Pion absorption above the Delta (1232) resonance. PMID- 9969158 TI - Spin-isospin strength distributions in f-p shell nuclei: A study of the 51V(n,p) and 59Co(n,p) reactions at 198 MeV. PMID- 9969159 TI - Fragmentation of Gamow-Teller strength observed in 117,120Sn(3He,t)117,120Sb charge-exchange reactions. PMID- 9969160 TI - One neutron pickup reactions in the 32S+144Sm and 32S+166Er systems at energies close to the Coulomb barrier. PMID- 9969161 TI - Ultradipole photon production in 40 and 50 MeV alpha -nucleus collisions. PMID- 9969162 TI - Novel probe of charge symmetry breaking: Deuteron-induced deuteron breakup. PMID- 9969163 TI - Breakup of intermediate-mass fragments, 8Be and 6Li, formed in the reaction 40Ar+Ag at 7.8A and 17A MeV. PMID- 9969164 TI - Alternatives for understanding qualitative features that dominate particle particle correlations in heavy-ion reactions of PMID- 9969165 TI - Search for entrance channel effects in the decay of the 164Yb compound nucleus at E* PMID- 9969166 TI - Formation and decay of 164Yb* in near- and below-barrier fusion reactions. PMID- 9969167 TI - Renormalization for optical model and unified model of nuclear reactions. PMID- 9969168 TI - Optical model analyses of 1.65 A GeV argon fragmentation: cross sections and momentum distributions. AB - An optical potential fragmentation model capable of predicting fragmentation cross sections and fragment momentum distributions is used to analyze recent measurements of 1.65 A GeV argon projectiles fragmenting in carbon and potassium chloride targets obtained with the Heavy Ion Spectrometer System (HISS) at the Lawrence Berkeley Laboratory Bevalac. The theoretical model uses an abrasion ablation-FSI (frictional spectator interaction) collision formalism to estimate elemental and isotopic production cross sections for comparison with the measured values. The collision momentum transfer model is incorporated into a Goldhaber formalism to analyze measured transverse and longitudinal distributions of the projectile fragments. Good agreement between theory and experiment is obtained for all observables. PMID- 9969170 TI - Hard-photon emission in 129Xe+197Au reaction at 44 MeV/nucleon. PMID- 9969169 TI - Role of heavy meson exchange in near threshold NN-->d pi. PMID- 9969172 TI - Nucleon flow and fragment flow in heavy ion reactions. PMID- 9969171 TI - Quasielastic nuclear response. PMID- 9969173 TI - Microscopic formulation of medium contributions to the first-order optical potential. PMID- 9969174 TI - Inclusive and exclusive production of eta mesons by pions. PMID- 9969175 TI - Fragmentation of 1.2 GeV per nucleon 139La. PMID- 9969176 TI - Production of pi +/-, K+/-, p, and p-bar in relativistic Au+Pt, Si+Pt, and p+Pt collisions. PMID- 9969177 TI - Systematic behavior of K/ pi ratio in relativistic nucleus-nucleus collisions. PMID- 9969178 TI - Geometry, scaling, and universality in the mass distributions in heavy ion collisions. PMID- 9969179 TI - Color transparency and final-state interactions in photonuclear charmonium production. PMID- 9969180 TI - Cloudy bag model for the S-D wave K-bar-N system. PMID- 9969181 TI - Beta asymmetry of the first forbidden 1/2(+)-->1/2(-) transition in 19Ne and its relationship to the parity nonconserving nucleon-nucleon interaction. PMID- 9969182 TI - Neutrino-nucleus quasifree neutral current reactions and the nucleon strange quark content. PMID- 9969183 TI - Investigation of the 13N(p, gamma )14O reaction using 13N radioactive ion beams. PMID- 9969184 TI - Half-life measurements for 61Ga, 63Ge, and 65As and their importance in the rp process. PMID- 9969185 TI - Thick-target yields of iodine isotopes from proton interactions in Te, and the double- beta decays of 128,130Te. PMID- 9969186 TI - Search for the beta + decay of 54Mn. PMID- 9969188 TI - Excitation function and isomeric cross-section ratio for the 61Ni(p, alpha )58Com,g process. PMID- 9969187 TI - Searches for proton radioactivity in odd Z drip-line nuclei from Z=61 to 67. PMID- 9969190 TI - Description of proton elastic scattering on 6,7,9,11Li with microscopic effective interaction. PMID- 9969189 TI - Low-energy resonances in 13C( alpha,n). PMID- 9969191 TI - Phase variation of the NN amplitude at 1.75 GeV/c. PMID- 9969192 TI - Examination of inconsistencies between the deformed potential model and folding models for analysis of inelastic hadron scattering. PMID- 9969193 TI - Semiclassical estimate of the Coulomb excitation of the giant dipole resonance in 208Pb. PMID- 9969194 TI - Erratum: Extraction of the multifragmentation time scale in intermediate energy heavy-ion reactions PMID- 9969195 TI - Statistical multistep direct reaction. PMID- 9969196 TI - Exotic density shapes in asymmetric heavy ion collisions at intermediate bombarding energies. PMID- 9969197 TI - Relativistic description of electron scattering on the deuteron. PMID- 9969198 TI - Effective mass of omega meson and NN omega interaction at finite temperature and density. PMID- 9969199 TI - Study of the beta -delayed neutron decay of 18N. PMID- 9969200 TI - Yrast level structure of the neutron deficient N=49 isotones 92Tc, 93Ru, 94Rh, and 95Pd up to high angular momentum. PMID- 9969201 TI - Electromagnetic decay properties of high spin states in 4391Tc48. PMID- 9969202 TI - Pion double charge exchange on natSe. PMID- 9969203 TI - Levels in 168Er above 2 MeV and the onset of chaos. PMID- 9969204 TI - Neutron scattering cross sections for 204,206Pb and neutron and proton amplitudes of E2 and E3 excitations. PMID- 9969205 TI - High spin structure of 84Y. PMID- 9969206 TI - Similarities and differences between the Gaussian and random phase approximation for the partition function. PMID- 9969207 TI - Signature inversion and change in triaxiality in 159Tm and 159Er. PMID- 9969208 TI - Structure study of 40Ca by alpha +36Ar cluster model. PMID- 9969209 TI - Sum rules in the proton-neutron interacting boson model: Generalized treatment and specific applications. PMID- 9969210 TI - Complex, energy-independent, local potential reproducing an absorptive phase shift and a bound state. PMID- 9969211 TI - Theoretical description of octupole correlations in the 138-148Xe nuclei. PMID- 9969212 TI - Comparison between the temperature and the time-dependent Hartree-Fock-Bogoliubov descriptions of the pairing interaction. PMID- 9969213 TI - Three-body halos: Gross properties. PMID- 9969214 TI - Exclusion of spuriousity through effective operators. PMID- 9969215 TI - Cranked Nilsson-Strutinsky model applied to high spin states in 22,23Na: Systematics of rotational isomers and band terminations in the A=20-26 region. PMID- 9969216 TI - From nuclear matter to finite nuclei. I. Parametrization of the Dirac-Brueckner G matrix. PMID- 9969217 TI - Fusion of 32S+154Sm at sub-barrier energies. PMID- 9969219 TI - Excitation functions of threshold reactions on 45Sc and 55Mn induced by 6 to 13 MeV neutrons. PMID- 9969218 TI - Elastoplasticity in dissipative heavy-ion collisions. PMID- 9969220 TI - Proton-proton correlations: Determination of the source size and lifetime from deep inelastic collisions of 58Ni+58Ni at 15 MeV/nucleon. PMID- 9969221 TI - Low-lying structure of 10Li in the reaction 11B(7Li,8B)10Li. PMID- 9969222 TI - Lifetimes of well characterized hot nuclei via small-angle particle-particle correlations: 40Ar+Ag (E/A=7.8 and 17 MeV). PMID- 9969224 TI - Target residues from the interaction of copper with 90 MeV/nucleon 6Li ions. PMID- 9969223 TI - Neutron-proton bremsstrahlung from low-energy heavy-ion reactions. PMID- 9969225 TI - Mass and transverse momentum dependence of dielectron production in p+d and p+p collisions at 4.9 GeV. PMID- 9969226 TI - Vector analyzing power measurement of pion scattering from polarized 7Li in the region of the Delta 33 resonance. PMID- 9969227 TI - Laser-driven inverse electronic bridge process: An optical tool for determining low-energy separation of nearby nuclear states. PMID- 9969228 TI - Inclusive spectra of stripping reactions induced by heavy ions. PMID- 9969229 TI - Azimuthal distribution in heavy-ion collisions. PMID- 9969230 TI - Pion electroproduction on proton and deuteron. PMID- 9969231 TI - Classical and quantum approach to light-particle correlations in intermediate energy heavy-ion reactions. PMID- 9969232 TI - Isobar excitation in parity-nonconserving proton-proton scattering. PMID- 9969233 TI - Enormous spin polarization in heavy-ion-induced one-nucleon transfer reactions. PMID- 9969234 TI - Statistical model analysis of fast-neutron-induced fission of U isotopes. PMID- 9969235 TI - Higher order effects in electromagnetic excitation with fast projectiles. PMID- 9969237 TI - Relativistic effects on polarization transfer observables for quasielastic proton nucleus scattering. PMID- 9969236 TI - Dynamic polarization potential for 11Li scattering. PMID- 9969238 TI - Dilepton production in nucleon-nucleon reactions with and without hadronic inelasticities. PMID- 9969239 TI - Detailed-balance tests of time-reversal invariance with interfering charged particle resonances. PMID- 9969240 TI - Projectile rapidity pions in 775 MeV/nucleon 139La+12C and 139La+139La reactions. PMID- 9969241 TI - High energy approximations for the total Born cross section for pair production in a screened Coulomb field. PMID- 9969242 TI - Hanbury-Brown-Twiss analysis in a solvable model. PMID- 9969244 TI - QCD sum rules for nucleons in nuclear matter III. PMID- 9969243 TI - Off-shell rho - omega mixing in QCD sum rules. PMID- 9969245 TI - Gauge invariance and the electromagnetic current of composite pions. PMID- 9969246 TI - A dependence of hadron-nucleus massive lepton pair production. PMID- 9969247 TI - Meson mass spectrum from relativistic equations in configuration space. PMID- 9969248 TI - Relativistic momentum space wave equations and meson spectroscopy. PMID- 9969249 TI - Study of dense helium plasma in the optimal hypernetted chain approximation. PMID- 9969251 TI - Continuum random phase approximation self-consistent approaches to the theory of isobaric analog resonances. PMID- 9969250 TI - Multipole mixing ratios of the 198 and 177 keV gamma -ray transitions in 169Tm. PMID- 9969252 TI - Finite range momentum and density dependent effective interaction and analysis of nuclear incompressibility. PMID- 9969253 TI - Vacuum-polarization corrections to solar-fusion rates. PMID- 9969254 TI - Self-energy of the pion. PMID- 9969255 TI - Low-lying surface vibrations in the pair-hopping model. PMID- 9969256 TI - Momentum transfer dependence of medium effects in the (e,e') longitudinal response. PMID- 9969257 TI - Possible evidence for particle-hole intruder analog multiplets in the Pb region. PMID- 9969258 TI - Superdeformed and hyperdeformed states in 56Ni. PMID- 9969259 TI - Microscopic calculation of in-medium proton-proton cross sections. PMID- 9969260 TI - Erratum: Self-consistent relativistic calculation of nucleon mean free path PMID- 9969261 TI - Spin-orbit and tensor potentials from polarized 6Li scattering. PMID- 9969262 TI - Electromagnetic dissociation of 238U at 120 MeV/nucleon. PMID- 9969263 TI - Maximum azimuthal anisotropy of neutrons from Nb-Nb collisions at 400A MeV and the nuclear equation of state. PMID- 9969265 TI - Single-particle spectral function of 16O. PMID- 9969264 TI - Analyzing power puzzle in low energy elastic Nd scattering. PMID- 9969266 TI - Pion elastic scattering on 28Si at T pi =400 MeV. PMID- 9969268 TI - NN correlations and relativistic Hartree-Fock in finite nuclei. PMID- 9969267 TI - Spin correlation measurements for p PMID- 9969269 TI - Spin-lattice relaxation of Ra in Tl and g factor of the 213Ram, tau =2.1 ms isomer. PMID- 9969270 TI - Octupole deformation in 149,151Sm nuclei. PMID- 9969271 TI - High-spin studies of 219Ac. PMID- 9969272 TI - Intermediate structure in the neutron-induced fission cross section of 236U. PMID- 9969273 TI - Comparison of Gamow-Teller strength in 37Ar and 37K and 37Cl neutrino cross sections. PMID- 9969274 TI - Multichannel study on the fragmentation of the 1g9/2 isobaric analog resonance in 53Mn. PMID- 9969275 TI - Nuclear g-factor measurement for the 21/2(+) isomeric state in 89Nb. PMID- 9969276 TI - Spatial orientation of nuclei: Mass deformation in 165-holmium. PMID- 9969277 TI - Superdeformed bands in 191Tl. PMID- 9969279 TI - Transition strengths and multiple band structure in 82Sr. PMID- 9969278 TI - Spectroscopy of the isotones 215Rn and 217Ra. PMID- 9969280 TI - Measurement and significance of Gamma gamma / Gamma for the 7117-keV 4(+) level of 18O. PMID- 9969281 TI - Level density of 57Co. PMID- 9969282 TI - Nuclear decay times of evaporation residues of 44Ti by crystal blocking method. PMID- 9969283 TI - Systematic relativistic Hartree-Fock calculation of deformed nuclei in s-d shell. PMID- 9969285 TI - Isovector spin-longitudinal and -transverse response of nuclei. PMID- 9969284 TI - Nuclear structure studies with (e,e'), ( pi, pi '), and ( gamma, pi ) reactions: Applications to 10B. PMID- 9969286 TI - Evidence for phase transitional behavior of even-even nuclei from differential observables. PMID- 9969287 TI - Symplectic pseudo-SU(3) model and B(E2; 01+-->21+) value of 238U. PMID- 9969288 TI - Microscopic description of the beta delayed deuteron emission from 6He. PMID- 9969289 TI - First-forbidden beta decay: Meson-exchange enhancement of the axial charge at A~16. PMID- 9969290 TI - Classical mappings of the symplectic model and their application to the theory of large-amplitude collective motion. PMID- 9969291 TI - Combinatorial nuclear level density by a Monte Carlo method. PMID- 9969293 TI - Single particle spectrum and spin-orbit splittings in relativistic mean field theory. PMID- 9969292 TI - Modeling complex nuclear spectra: Regularity versus chaos. PMID- 9969295 TI - E2 properties of nuclei far from stability and the proton-halo problem of 8B. PMID- 9969294 TI - Deep pionic bound states in a nonlocal optical potential. PMID- 9969296 TI - Shape dependence of the deuteron radius. PMID- 9969297 TI - Charge correlations and transverse momenta observed in multifragmentation of 1 GeV/nucleon Au projectiles. PMID- 9969298 TI - Polarized deuteron capture by 3He and 3H at and above the fusion resonance region. PMID- 9969299 TI - Anomalous anisotropy of fission fragments in near- and sub-barrier complete fusion-fission reactions of 16O+232Th, 19F+232Th, and 16O+238U. PMID- 9969300 TI - Entrance channel effects in the fusion-fission time scales from studies of prescission neutron multiplicities. PMID- 9969301 TI - Investigations of complete and incomplete fusion in 12C+93Nb and 16O+89Y by recoil range measurements. PMID- 9969303 TI - Quasielastic proton knockout from 16O. PMID- 9969302 TI - Light-particle correlations with evaporation residues in the 40Ca+12C reaction at E(40Ca)=450 MeV. PMID- 9969304 TI - Prescission and postscission charged particle emissions from the 19F+159Tb reaction. PMID- 9969305 TI - Rainbowlike effects in (3He, alpha ) reactions. PMID- 9969307 TI - Emission of light charged particles in photon induced fission. PMID- 9969306 TI - Quasimolecular states of 24Mg excited in the 16O+12C interaction. PMID- 9969308 TI - Preequilibrium (p,p') measurements and calculations for 90Zr and neighboring nuclei for incident energies up to 200 MeV. PMID- 9969309 TI - Fragment isotope spectra from the 36Ar + Ag reaction at 35 MeV/nucleon. PMID- 9969310 TI - Selective population of states in fission fragments from the 32S+24Mg reaction. PMID- 9969311 TI - Heavy-ion resonance and statistical fission competition in the 24Mg+24Mg system at Ec.m.=44.4 MeV. PMID- 9969312 TI - Study of energy deposition in heavy-ion reactions. PMID- 9969314 TI - Neutron skin effect in preequilibrium nucleon emissions. PMID- 9969313 TI - Hypernuclear and Lambda -spin polarizations produced in the ( pi +,K+) reaction. PMID- 9969315 TI - Systematics of preequilibrium contributions in (n,p) reactions at 14 MeV. PMID- 9969316 TI - Systematic study of subbarrier fusion in rare-earth nuclei. PMID- 9969317 TI - Double-doorway model for pion-nucleon elastic scattering in the S11 channel. PMID- 9969318 TI - Equivalent local potentials to multiple scattering calculations of nucleon nucleus scattering. PMID- 9969320 TI - Neutrino-induced reactions on 12C within the continuum random phase approximation. PMID- 9969319 TI - Imaginary part of the optical potential for preequilibrium processes. PMID- 9969321 TI - gamma gamma physics at relativistic heavy-ion colliders. PMID- 9969322 TI - Kinetics of an expanding pion gas and low-mass dilepton emission. PMID- 9969323 TI - Subthreshold antiproton production in nucleus-nucleus collisions. PMID- 9969324 TI - Baryon-baryon components in the deuteron as quark-exchange currents. PMID- 9969325 TI - Kaon-nucleon scattering amplitudes and Z* enhancements from quark Born diagrams. PMID- 9969326 TI - Properties of the rho meson in nuclear matter. PMID- 9969327 TI - QCD sum rules for Lambda hyperons in nuclear matter. PMID- 9969328 TI - Total cross sections and thermonuclear reaction rates for 9Be( alpha,n)12C. PMID- 9969330 TI - Elastic scattering and fusion of 16O+59Co at near barrier energies: A signature for long range fusion potentials. PMID- 9969329 TI - Deep inelastic collisions in the system 40Ar+232Th at 31 MeV/nucleon. PMID- 9969331 TI - Decay of 98Rh. PMID- 9969332 TI - Correlation between epsilon / Delta and the P factor. PMID- 9969333 TI - Critical role of 122,123,124Te in s-process nucleosynthesis. PMID- 9969334 TI - Erratum: Analysis of the reaction pi +d-->pp to 500 MeV PMID- 9969335 TI - Collisions between 106Cd and 54Fe at 30 MeV above the Coulomb barrier by high resolution gamma gamma coincidences. PMID- 9969336 TI - Identical bands in 77Sr, 78Sr, and 78Rb: Evidence for a very good spectator orbital. PMID- 9969337 TI - Estimation of the time scale of last chance alpha emission using an "atomic clock" PMID- 9969338 TI - Prolate collectivity in 187Tl. PMID- 9969339 TI - Observation of the new neutron-rich nuclide 208Hg. PMID- 9969340 TI - Three-body 3He photodisintegration in the Delta region. PMID- 9969341 TI - Reaction gamma d--> pi 0d and the small components of the deuteron wave function. PMID- 9969342 TI - Phenomenological signature for the onset of strong octupole correlations. PMID- 9969343 TI - Medium effects on subthreshold kaon production in heavy-ion collisions. PMID- 9969345 TI - Parity violation in charged particle nuclear reactions. PMID- 9969344 TI - Optical-model description of time-reversal violation in neutron-nucleus scattering. PMID- 9969346 TI - Improved limits on time-reversal-violating, tensor weak couplings. PMID- 9969347 TI - Determination of inelastic scattering amplitudes from (p,p' gamma ) reactions. PMID- 9969348 TI - Threshold electrodisintegration in the A=3 system. PMID- 9969350 TI - Weakly bound states of a three-body system. PMID- 9969349 TI - Non-adiabatic contributions to static two-pion-exchange nuclear potentials. PMID- 9969351 TI - Impact of pp-->pp pi 0 data to negative-pion absorption on proton pairs. PMID- 9969352 TI - Sub-barrier fusion in generalized boson models. PMID- 9969353 TI - Self-consistent solution of the Schwinger-Dyson equations for the nucleon and meson propagators. PMID- 9969354 TI - Density-dependent effective interactions. PMID- 9969355 TI - Comparison between relativistic and nonrelativistic models of the nucleon-nucleon effective interaction. I. Normal-parity isoscalar transitions. PMID- 9969356 TI - Role of heavy-meson exchange in pion production near threshold. PMID- 9969357 TI - Recoil-separated gamma-ray spectroscopy of 47Ti, 47V, 47Cr, 48V, and 48Cr. PMID- 9969358 TI - Electroexcitation of low-multipolarity magnetic transitions in 36Ar and 38Ar. PMID- 9969359 TI - Origin of correlations between evaporation protons and discrete gamma rays in heavy-ion fusion-evaporation reactions. PMID- 9969361 TI - Comparison of the Porter-Thomas distribution with neutron resonance data of even even nuclei. PMID- 9969360 TI - Evolution of deformation in the neutron-rich Zr region from excited intruder state to the ground state. PMID- 9969362 TI - Exact solutions and constrained Hartree-Fock spectra in a soluble triaxial quasispin model. PMID- 9969364 TI - Dependence on the mass number of energy quantities of a Lambda in hypernuclei with the cosh and the Gaussian potential. PMID- 9969363 TI - Nuclear charge radii in modern mass formulas. PMID- 9969366 TI - Quantum theory of large amplitude collective motion: Natural fit between the Born Oppenheimer and Kerman-Klein methods. PMID- 9969365 TI - Demonstration of the auxiliary-field Monte Carlo approach for sd-shell nuclei. PMID- 9969367 TI - Quantum theory of large amplitude collective motion: Bosonization of all degrees of freedom. PMID- 9969368 TI - Cranking Bohr-Mottelson Hamiltonian applied to superdeformed bands in A~190 region. PMID- 9969369 TI - Influence of nuclear structure on the characteristics of light pionic atoms. PMID- 9969370 TI - Fine structure of cluster decays. PMID- 9969371 TI - Three-dimensional cranking at finite temperature. PMID- 9969372 TI - From nuclear matter to finite nuclei. II. Relativistic theories for finite nuclei. PMID- 9969374 TI - Excitation functions and isomeric cross section ratios of the 63Cu(n, alpha )60Com,g, 65Cu(n, alpha )62Com,g, and 60Ni(n,p)60Com,g processes from 6 to 15 MeV. PMID- 9969373 TI - Energy dissipation and multifragment decay in the 3He+natAg system. PMID- 9969375 TI - 4He(4He,3He)5He(g.s.) reaction at 118 MeV, and its distorted wave Born approximation interpretation. PMID- 9969376 TI - Quasielastic scattering of 12,14Be on 12C. PMID- 9969377 TI - 13C(e,p0,1)12B differential cross section. PMID- 9969378 TI - Search for resonances in multiphoton final states from low-energy e+e- scattering. PMID- 9969379 TI - 29Si(d,3He)28Al reaction at 29 MeV. PMID- 9969381 TI - Tests for equilibration of 149Tb* composite nuclei produced in the reactions 337 MeV 40Ar+natAg and 640 MeV 86Kr+63Cu. PMID- 9969380 TI - Light charged particle and intermediate mass fragment emission in the reaction 640 MeV 86Kr+63Cu. PMID- 9969382 TI - Intermediate mass fragments from the reactions 486, 550, 640, and 730 MeV 86Kr+63Cu. PMID- 9969383 TI - Density distribution of 11Li and proton elastic scattering from 9Li and 11Li. PMID- 9969384 TI - Optical model calculations for the elastic scattering of intermediate energy alpha particles. PMID- 9969385 TI - Local representation of the exchange nonlocality in n-16O scattering. PMID- 9969386 TI - Mass dependence of critical behavior in nucleus-nucleus collisions. PMID- 9969387 TI - Coulomb and nuclear excitation in intermediate-energy heavy-ion collisions. PMID- 9969388 TI - Double-folding model for heavy-ion optical potential: Revised and applied to study 12C and 16O elastic scattering. PMID- 9969390 TI - Thermal quark production in ultrarelativistic nuclear collisions. PMID- 9969389 TI - Two charged particle and transverse energy correlations in Si+Pb collisions at 14.6A GeV/c. PMID- 9969391 TI - Memory effects in relativistic heavy ion collisions. PMID- 9969392 TI - Nucleon solution of the Faddeev equation in the Nambu-Jona-Lasinio model. PMID- 9969393 TI - Influence of the Delta Delta -meson coupling on nucleon and Delta properties in nuclear matter. PMID- 9969395 TI - K pi =6(+) and 8(-) isomer decays in 172Hf and Delta K=8 E1 transition rates. PMID- 9969394 TI - Vector analyzing power iT11 in pi d elastic scattering at 49 MeV. PMID- 9969397 TI - QCD Fokker-Planck equations with color diffusion. PMID- 9969396 TI - Emission of alpha particles during the spontaneous fission of 244Pu. PMID- 9969399 TI - Opposite-parity bands in 153Eu. PMID- 9969398 TI - Absence of anomalous entrance channel effects in sub-barrier heavy ion fusion. PMID- 9969400 TI - Quantum interference effects in N* electroproduction and propagation in nuclei. PMID- 9969402 TI - Deformed atomic nuclei with degeneracies of the nucleonic levels higher than 2. PMID- 9969401 TI - Correlation between quantized-alignment and identical-band mechanisms. PMID- 9969404 TI - Nucleon resonances in nuclei and quark exchange. PMID- 9969403 TI - Rapidity dependence of soft mesons as a signature of resonance matter production in nucleus-nucleus collisions. PMID- 9969405 TI - Separation of the 2H(e,e'p) structure functions up to 0.9 GeV/c momentum transfer. PMID- 9969406 TI - Effects of a quark-model-based nucleon- Delta potential on the two-nucleon system above pion threshold. PMID- 9969408 TI - Two pion exchange nucleon-nucleon potential: The minimal chiral model. PMID- 9969407 TI - New effective internucleon forces in microscopic alpha -cluster model. PMID- 9969409 TI - Renormalization of the P- and T-odd nuclear potentials by the strong interaction and enhancement of P-odd effective field. PMID- 9969410 TI - Nucleon-nucleon potentials and their test with bremsstrahlung. PMID- 9969411 TI - Multiphonon vibrational states in deformed nuclei. PMID- 9969412 TI - An excited state of 229Th at 3.5 eV. PMID- 9969413 TI - Electron-capture delayed fission properties of the new isotope 238Bk. PMID- 9969415 TI - Alpha decay of 216At and the level structure of 212Bi. PMID- 9969414 TI - beta -delayed alpha decay of 17N. PMID- 9969416 TI - Oblate to prolate shape hindrance in 121I. PMID- 9969417 TI - Rotational bands and neutron alignments in neutron rich odd-A cadmium isotopes. PMID- 9969418 TI - High spin states and shell model description of the neutron deficient nuclei 90Ru and 91Ru. PMID- 9969419 TI - Effects of 10Li virtual states on the structure of 11Li. PMID- 9969420 TI - Unstable infinite nuclear matter in stochastic mean field approach. PMID- 9969421 TI - Identical energy bands of uranium isotopes in the interacting boson model. PMID- 9969422 TI - Measurable decay modes of barium isotopes via exotic cluster emissions. PMID- 9969423 TI - Photopion production in 3H and 3He. PMID- 9969424 TI - Robust predictions of the interacting boson approximation model. PMID- 9969425 TI - Energy-shell contributions of the three-particle-three-hole excitations. PMID- 9969426 TI - Canonical number projection in a simple nuclear model. PMID- 9969427 TI - Relativistic Coulomb sum rules for (e,e'). PMID- 9969429 TI - Medium modifications to the omega -meson mass in the Walecka model. PMID- 9969428 TI - Specific heat and shape transitions in light sd nuclei. PMID- 9969430 TI - Analysis of the spreading width of the particle-hole giant resonances. PMID- 9969432 TI - Random-phase-approximation-type vertex corrections to the axial-vector current. PMID- 9969431 TI - Simple approximation for the starting-energy-independent two-body effective interaction with applications to 6Li. PMID- 9969433 TI - Octupole-induced dipole moments of very deformed nuclei. PMID- 9969434 TI - Competing reaction mechanisms for the 16,17,18O+10,11B and 19F+9Be systems. PMID- 9969435 TI - Isotopic product distributions in the near symmetric mass region in proton induced fission of 238U. PMID- 9969436 TI - Asymmetries in 100 MeV pi +/ pi --3H PMID- 9969437 TI - Interference effects in non-analog pion double charge exchange. PMID- 9969438 TI - Inclusive protonlike production cross sections from 0.757 GeV/nucleon La+La collisions. PMID- 9969440 TI - Dirac coupled channel calculations for proton inelastic scattering from spherically symmetric nuclei for projectile energies of 362, 500, and 800 MeV. PMID- 9969439 TI - Neutron transition densities for 48Ca from proton scattering at 200 and 318 MeV. PMID- 9969442 TI - Phenomenological transition amplitudes for NN-->N Delta at 800 MeV. PMID- 9969441 TI - Enhanced emissions of hard photons in heavy ion reactions by the particle correlation effect. PMID- 9969443 TI - Extraction of neutron densities from elastic proton scattering by 206,207,208Pb at 650 MeV. PMID- 9969444 TI - Global optical potentials for emitted alpha particles. PMID- 9969445 TI - Relativistic cluster dynamics of nucleons and mesons. II. Formalism and examples. PMID- 9969446 TI - Nuclear fragmentation and its parallels. PMID- 9969447 TI - Quantal inversion of the cross section for the elastic scattering of 200 MeV protons from 12C. PMID- 9969448 TI - Comparison of the quasielastic (e,e'p) and the ( gamma,p) reactions. PMID- 9969449 TI - Color collective effects at the early stage of ultrarelativistic heavy-ion collisions. PMID- 9969450 TI - What can we learn from a second phi meson peak in ultrarelativistic nuclear collisions? PMID- 9969452 TI - Two-pion exchange and chiral symmetry restoration. PMID- 9969451 TI - Gluon multiplication in high energy heavy ion collisions. PMID- 9969453 TI - Electromagnetic gauge invariance of chiral hybrid quark models. PMID- 9969455 TI - Alpha decay of 231U to levels in 227Th. PMID- 9969454 TI - Negative pion-nucleus elastic scattering at 20 and 40 MeV. PMID- 9969456 TI - Two-neutrino double beta decay of 48Ca. PMID- 9969458 TI - Half-lives for two neutrino double-beta-decay transitions to first 2(+) excited states. PMID- 9969457 TI - Simple parametrization of fragment reduced widths in heavy ion collisions. AB - A systematic analysis of the observed reduced widths obtained in relativistic heavy ion fragmentation reactions is used to develop a phenomenological parametrization of these data. The parametrization is simple, accurate, and completely general in applicability. PMID- 9969459 TI - Three-body resonances by complex scaling. PMID- 9969460 TI - Checking a neutron halo from elastic scattering. PMID- 9969461 TI - Comment on "Macroscopic models for the fusion of very heavy ions" PMID- 9969462 TI - Reply to "Comment on 'Macroscopic models for the fusion of very heavy ions' " PMID- 9969463 TI - Comment on "Elastic scattering of 318 MeV 6Li from 12C and 28Si: Unique phenomenological and folding-model potentials" and the validity of the M3Y effective interaction. PMID- 9969464 TI - Reply to "Comment on 'Elastic scattering of 318 MeV 6Li from 12C and 28Si: Unique phenomenological and folding-model potentials' and the validity of the M3Y effective interaction" PMID- 9969465 TI - Excitation energy deposition in central collisions of 40A MeV 40Ar with 232Th. PMID- 9969466 TI - Large fragmentation of the pairing-vibration PMID- 9969467 TI - Intermittency and fragmentation of target residue in high-energy nuclear interactions. PMID- 9969468 TI - Limits for the 3 alpha branching ratio of the decay of the 7.65 MeV, 02+ state in 12C. PMID- 9969469 TI - The "hot CNO cycle" 13N(p, gamma ) resonance energy and the 18Ne mass. PMID- 9969470 TI - Global systematics of unique parity quasibands in odd-A collective nuclei. PMID- 9969471 TI - s-wave pion-nucleus interaction and weak coupling constants. PMID- 9969473 TI - E2 contribution to the 8B-->p+7Be Coulomb dissociation cross section. PMID- 9969472 TI - Novel aspects of hypernuclei. PMID- 9969474 TI - Role of intrinsic width in fragment momentum distributions in heavy ion collisions. AB - It is demonstrated that the intrinsic widths incorporating correlations in conjunction with dynamical contributions give better agreement with experiments for collisions in the energy range of 200A MeV to 2A GeV than using only intrinsic widths without correlations. The sensitivity of the intrinsic width decreases with increasing projectile mass. A simple recipe for calculating intrinsic width with correlations is presented. PMID- 9969475 TI - Fragmentation barriers of toroidal and bubble nuclei. PMID- 9969476 TI - Tensor analyzing powers for 2H(d,p)3H and 2H(d,n)3He at deuteron energies of 25, 40, 60, and 80 keV. PMID- 9969478 TI - Nucleon-nucleon interaction with consistently soft form factors for one and two pion exchange. PMID- 9969477 TI - Deep inelastic scattering on the deuteron in the Bethe-Salpeter formalism: Scalar meson exchange. PMID- 9969479 TI - Effects of the three-body force in three-nucleon systems. PMID- 9969481 TI - Dynamical model for correlated two-pion exchange in the NN interaction. PMID- 9969480 TI - Coulomb correction calculations of pp bremsstrahlung. PMID- 9969482 TI - Nucleon-nucleon interaction from meson exchange and nucleonic structure. PMID- 9969483 TI - Slow proton production in deep-inelastic neutrino scattering on deuterium. PMID- 9969484 TI - P,T-violating nuclear matrix elements in the one-meson exchange approximation. PMID- 9969486 TI - The Q value for the 26Alm superallowed beta decay. PMID- 9969485 TI - Excitation function for the population of the 4.51 MeV state of 27Al in inelastic proton scattering: Evidence for 6(-) strength? PMID- 9969487 TI - Limits on single- and multinucleon decays in 127I by inclusive measurements of nuclear gamma and x rays. PMID- 9969488 TI - Gamma ray studies of neutron-rich sdf shell nuclei produced in heavy ion collisions. PMID- 9969489 TI - Onset of collectivity in the odd-odd nucleus 72As. PMID- 9969490 TI - Excited states built on the 6(-) isomer in 3786Rb49. PMID- 9969491 TI - First observation of the beta -delayed proton decay of 52Ni. PMID- 9969492 TI - Decay modes of high-lying single-particle states in 209Pb. PMID- 9969493 TI - Energy systematics of even-even nuclei in the NpNn scheme. PMID- 9969495 TI - Relativistic description of Lambda, Sigma, and Xi hypernuclei. PMID- 9969494 TI - Broken O(6) symmetry of IBM1 with three-body potential. PMID- 9969496 TI - Constraints on the nuclear compressibility from analysis of the breathing mode and density differences of lead isotopes. PMID- 9969498 TI - tau compression in the SO(5) scheme. PMID- 9969497 TI - K pi =1(+) pairing interaction and moments of inertia of superdeformed rotational bands in atomic nuclei. PMID- 9969499 TI - Empirical proton-neutron interactions near closed shells: A simple shell-model approach. PMID- 9969500 TI - Stretched spin strength in 26Mg and 30Si. PMID- 9969501 TI - Tensor polarization in elastic electron-deuteron scattering in the momentum transfer range 3.8 <= Q <= 4.6 fm-1. PMID- 9969502 TI - Breakup of 87 MeV 11B. PMID- 9969503 TI - Observation of 12C cluster transfer by angular correlation measurements. PMID- 9969504 TI - Fission of heavy nuclei induced by stopped antiprotons. I. Inclusive characteristics of fission fragments. PMID- 9969505 TI - Measurement of low energy K+ total cross sections on N=Z nuclei. PMID- 9969506 TI - One- and two-proton transfer reactions in 32S+64Ni and 28Si+68Zn at near-barrier energies. PMID- 9969507 TI - 3He( gamma,pd) cross sections with tagged photons below the Delta resonance. PMID- 9969508 TI - Microscopic coupled-channel description of pion inelastic scattering from rotational nuclei. PMID- 9969509 TI - Comparison of fast cascade plus statistical models for heavy ion induced multifragmentation reactions. PMID- 9969510 TI - 12C+12C elastic scattering potentials obtained by unifying phase-shift analysis with the modified Newton-Sabatier inverse method. PMID- 9969512 TI - Role of mass renormalization in adiabatic quantum tunneling. PMID- 9969511 TI - Role of the number of open channels in the dynamics of the dinucleus binary decay. PMID- 9969513 TI - Total neutron-nucleus cross sections and color transparency. PMID- 9969514 TI - Effect of Coulomb interaction in quasifree scattering and quasifree reactions in three body breakup processes. PMID- 9969515 TI - Relativistic meson exchange and isobar currents in electron scattering: Noninteracting Fermi gas analysis. PMID- 9969517 TI - The astrophysical reactions 12C( alpha, gamma )16O and 7Be(p, gamma )8B and Coulomb dissociation experiments. PMID- 9969516 TI - Role of correlated two-pion exchange in pi N scattering. PMID- 9969518 TI - Effects of meson-exchange currents on the (e PMID- 9969519 TI - Multinucleon mechanisms in ( gamma,N) and ( gamma,NN) reactions. PMID- 9969520 TI - Transverse momentum dependence of dileptons from parton matter produced in ultrarelativistic heavy-ion collisions. PMID- 9969522 TI - Pion-nucleon partial-wave analysis with fixed-t dispersion relation constraints. PMID- 9969521 TI - Looking for quark droplets in ultrarelativistic collisions. PMID- 9969523 TI - Nuclear dependence of the Drell-Yan process in relativistic heavy ion collisions. PMID- 9969524 TI - Color transparency and Dirac-based spin effects in (e,e'p) reactions. PMID- 9969525 TI - Meson exchange model for pi rho scattering. PMID- 9969526 TI - Meson exchange effects in parity violating electron-deuteron scattering. PMID- 9969527 TI - New T=0 strength in 16O at Ex=24 to 27 MeV. PMID- 9969528 TI - 206Pb states homologous to the 1.484 MeV, 11/2(-) state of 205Tl. PMID- 9969529 TI - Proton evaporation time scales from longitudinal and transverse two-proton correlation functions. PMID- 9969531 TI - Differential equations for semiclassical and quantum densities. PMID- 9969530 TI - Decays of 116Sb isomers to levels in 116Sn. PMID- 9969533 TI - New parametrization of the optical potential. PMID- 9969532 TI - Collective effects in the nuclear interactions of charmonium at low energy. PMID- 9969534 TI - Ideal quarks and mesons in the relativistic quark model. PMID- 9969535 TI - g factors of high spin states in 154Dy. PMID- 9969537 TI - Collective modes and response functions of relativistic asymmetric nuclear matter. PMID- 9969536 TI - Neck formation and sub-barrier fusion of heavy-ion systems: 64Ni+100Mo and 80Se+80Se. PMID- 9969538 TI - A dependence of R= sigma L/ sigma T and the Q2 dependence of nuclear shadowing. PMID- 9969539 TI - Ground-state correlation effects in extended random phase approximation calculations. PMID- 9969540 TI - Complex conjugate pairs in stationary Sturmian eigenstates. PMID- 9969542 TI - Nonlinear scalar coupling models and proton-nucleus scattering observables. PMID- 9969541 TI - Lambda (1405) and meson-baryon interactions in a quark model. PMID- 9969543 TI - Coulomb reacceleration as a clock for nuclear reactions: A two-dimensional model. PMID- 9969544 TI - Experimental evidence for axial asymmetry and hexadecapole deformation in 179Os. PMID- 9969545 TI - Reply to "Comment on 'Shadow model for sub-barrier fusion applied to light systems' " PMID- 9969546 TI - Comment on "Lack of evidence for a superdeformed band in 192Pb" PMID- 9969547 TI - Reply to "Comment on 'Lack of evidence for a superdeformed band in 192Pb' " PMID- 9969549 TI - Reply to "Comment on 'Influence of bulk properties on the surface structure of finite nuclei' " PMID- 9969548 TI - Comment on "Influence of bulk properties on the surface structure of finite nuclei" PMID- 9969550 TI - Erratum: Sub-barrier one- and two-neutron pickup measurements in 32S+93Nb, 98,100Mo reactions at 180 degrees PMID- 9969551 TI - Erratum: Criterion for the applicability of standard thermodynamics in heavy ion collisions PMID- 9969552 TI - Energy dependence of multifragmentation in 84Kr+197Au collisions. PMID- 9969553 TI - Excitation function for 4He( pi +,pp)2H two-nucleon absorption across the Delta resonance. PMID- 9969555 TI - Coulomb effects in deuteron breakup by proton impact. PMID- 9969554 TI - Complete decay out of the superdeformed band in 133Nd. PMID- 9969557 TI - Possible way out of the (p,n) puzzle. PMID- 9969556 TI - Neutron halo effect on direct neutron capture and photodisintegration. PMID- 9969558 TI - Intrinsic charge radius of the neutron: Discrepancy between the Garching and Dubna results. PMID- 9969559 TI - Angular momentum dependence of the parity splitting in nuclei with octupole correlations. PMID- 9969560 TI - Evidence for the ground-state proton decay of 105Sb. PMID- 9969561 TI - Multinucleon transfer reactions in 32S+208Pb close to the Coulomb barrier. PMID- 9969562 TI - Inclusive electron scattering and pion degrees of freedom in light nuclei. PMID- 9969563 TI - Preequilibrium spin effects in Feshbach-Kerman-Koonin and exciton models and application to high-spin isomer production. PMID- 9969564 TI - Momentum distribution of projectile fragments and nuclear shape. PMID- 9969565 TI - Resonant P33 S1+(3/2)(q2) electroproduction multipole amplitude and the Delta N gamma scalar form factor GC*(q2). PMID- 9969566 TI - Analyzing power measurements in pion deuteron absorption at low energies. PMID- 9969567 TI - Analytic solution of the harmonic-oscillator Faddeev equations for three nonidentical particles. PMID- 9969568 TI - Deformed Gaussian orthogonal ensemble analysis of the interacting boson model. PMID- 9969569 TI - Coulomb instability of hot nuclei with derivative scalar coupling. PMID- 9969570 TI - Few-nucleon forces from chiral Lagrangians. PMID- 9969571 TI - Deuteron properties using a truncated one pion exchange potential. PMID- 9969572 TI - Construction of high-quality NN potential models. PMID- 9969573 TI - Levels of 232U fed in 236Pu alpha decay. PMID- 9969574 TI - 3s-proton occupancies in 204Hg and 206Pb. PMID- 9969575 TI - Nuclear structure of 109Sb. PMID- 9969576 TI - Broken pairs and evolution of collectivity in the A PMID- 9969577 TI - Low-multipolarity magnetic transitions in 30Si, 32S, and 34S studied by 180 degrees electron scattering. PMID- 9969578 TI - Self-consistent collective coordinate method in nuclear rotation and wobbling motion at high spin. PMID- 9969579 TI - Microscopic description of the anisotropy in alpha decay. PMID- 9969580 TI - Nuclear densities and the statistics of nucleonic constituents. PMID- 9969581 TI - Three-body resonances in 6He, 6Li, and 6Be, and the soft dipole mode problem of neutron halo nuclei. PMID- 9969582 TI - Parity violation in heavy nuclei in a relativistic Hartree-Fock approximation. PMID- 9969583 TI - Energy weighted sum rules for spectral functions in nuclear matter. PMID- 9969584 TI - Quasiparticle random phase approximation analysis of the double beta decay of 100Mo to the ground state and excited states of 100Ru. PMID- 9969585 TI - Nuclear Schwinger-Dyson formalism applied to finite baryon density. I. Formulation. PMID- 9969586 TI - Nuclear Schwinger-Dyson formalism applied to finite baryon density. II. Numerical calculations and medium effects of meson self-energies. PMID- 9969587 TI - Proton total reaction cross sections for 42Ca, 44Ca, and 48Ca between 21 and 48 MeV. PMID- 9969588 TI - Q value for the 34Cl superallowed beta decay. PMID- 9969589 TI - Multipole decomposition of the 16O(p,n)16F and 18O(p,n)18F reactions at 494 MeV. PMID- 9969590 TI - Polarization observables in pi + 6Li scattering: Analyzing powers iT11 and tau 22. PMID- 9969591 TI - Spin-isospin strength distributions for fp shell nuclei: Results for the 55Mn(n,p), 56Fe(n,p), and 58Ni(n,p) reactions at 198 MeV. PMID- 9969592 TI - Study of in-medium NN inelastic cross section from relativistic Boltzmann-Uehling Uhlenbeck approach. PMID- 9969593 TI - Intermediate mass fragment yields from fusion and non-fusion processes in nucleus nucleus collisions in Fermi energy domain: An integrated dynamical approach. PMID- 9969594 TI - Optical model analyses of heavy ion fragmentation in hydrogen targets. AB - Quantum-mechanical optical-model methods for calculating cross sections for the fragmentation of high-energy heavy ions by hydrogen targets are presented. The cross sections are calculated with a knockout-ablation collision formalism which has no arbitrary fitting parameters. Predictions of elemental production cross sections from the fragmentation of 1.2A GeV 139La nuclei and of isotope production cross sections from the fragmentation of 400A MeV 32S nuclei are in good agreement with recently reported experimental measurements. PMID- 9969595 TI - Delta excitations in nuclei and their decay properties. PMID- 9969596 TI - Dynamical effects in the growth of density instabilities. PMID- 9969598 TI - Cluster structures in 10Be from the 7Li( alpha,p)10Be reaction. PMID- 9969597 TI - Extraction of critical exponents from very small percolation lattices. PMID- 9969599 TI - Interactions in hydrogen of relativistic neon to nickel projectiles: Total charge changing cross sections. PMID- 9969601 TI - Intermittency and correlations in 16O+Ag/Br interactions at 2.1 GeV/nucleon. PMID- 9969600 TI - Composite particle production in relativistic Au+Pt, Si+Pt, and p+Pt collisions. PMID- 9969602 TI - Revised formula of pion interferometry. PMID- 9969603 TI - Thermostatic properties and Coulomb instability of highly excited nuclei. PMID- 9969604 TI - Probing the space-time structure of quark and gluon transport in proton-nucleus collisions at collider energies. PMID- 9969605 TI - Poincare covariant particle dynamics. I. Intranuclear cascade model. PMID- 9969606 TI - Poincare covariant particle dynamics. II. Fragmentation for ultrarelativistic reactions. PMID- 9969607 TI - Color transparency in the deuteron. PMID- 9969608 TI - Effective 1/Nc expansion in the Nambu-Jona-Lasinio model. PMID- 9969609 TI - Search for a 17 keV neutrino in the internal bremsstrahlung spectrum of 125I. PMID- 9969610 TI - Is there large weak mixing in heavy nuclei? PMID- 9969611 TI - Differential cross sections of projectilelike fragments from 18O and 40Ar at E/A=80 MeV. PMID- 9969612 TI - New approach to spin assignments of intermediate structures in 12C(16O,12C PMID- 9969613 TI - High spin states of 84Sr. PMID- 9969614 TI - Alpha radioactivity above 100Sn including the decay of 108I. PMID- 9969615 TI - Anomalous populations of particle-unbound states in 10B. PMID- 9969616 TI - Collective flow by the azimuthal correlation of projectile fragments in relativistic heavy-ion collisions. PMID- 9969617 TI - Properties of intruder bands in the Os-Pt-Hg-Pb region. PMID- 9969618 TI - Charge distribution of projectile fragments in high-energy heavy-ion collisions. PMID- 9969619 TI - Approximation for the algebraic S matrix with an angular momentum dependent potential parameter. PMID- 9969620 TI - Investigating the multiparticle decay in intermediate energy heavy ion collisions. PMID- 9969621 TI - Determination of the isotensor symmetry energy for the giant dipole resonance. PMID- 9969622 TI - Nuclear shell-model calculations for 6Li and 14N with different NN potentials. PMID- 9969623 TI - Klein-Gordon versus relativistic Schrodinger equations in pion-nucleus scattering. PMID- 9969624 TI - Comment on "Evidence for a nuclear halo from 11Li elastic scattering measured at 637 MeV incident energy on a 12C target" PMID- 9969625 TI - Comment on "Orbitial M1 versus E2 strength in deformed nuclei: A new energy weighted sum rule" PMID- 9969626 TI - Reply to "Comment on 'Orbital M1 versus E2 strength in deformed nuclei: A new energy weighted sum rule' " PMID- 9969627 TI - Comment on " alpha -decay properties of neutron-deficient polonium and radon nuclei" PMID- 9969628 TI - Reply to "Comment on ' alpha -decay properties of neutron-deficient polonium and radon nuclei' " PMID- 9969629 TI - Erratum: Evidence for the statistical and sequential nature of 16O breakup into four alphas PMID- 9969630 TI - Experimental study of the reaction pp-->pp pi 0 in the energy range 600-900 MeV. PMID- 9969632 TI - Critical enhancement of the in-medium nucleon-nucleon cross section at low temperatures. PMID- 9969631 TI - Finite 3 pi cut approximation for the pi NN-bar form factor. PMID- 9969634 TI - Antiproton-proton partial-wave analysis below 925 MeV/c. PMID- 9969633 TI - Exact solution of the four-body Faddeev-Yakubovsky equations for the harmonic oscillator. PMID- 9969635 TI - 2H( gamma,p)n cross section between 20 and 440 MeV. PMID- 9969636 TI - Recoil distance lifetime measurements of states in the oblate dipole bands of 197,198Pb. PMID- 9969637 TI - Structure of the four quasiparticle band in 84Sr. PMID- 9969638 TI - Decay of 0(+) analogue state of 120Sb. PMID- 9969639 TI - Neutron i13/2 intruder band in 139Sm. PMID- 9969640 TI - Transition probabilities between high spin states in 88Mo and 90Mo. PMID- 9969642 TI - Nonlinear resonance in the time-dependent Hartree-Fock manifold. PMID- 9969641 TI - Deformation properties of the scissors mode in the generalized coherent state model. PMID- 9969643 TI - "Hidden" world of virtually excited clusters in atomic nuclei and its possible observation in quasielastic knockout of clusters by 1 GeV protons. PMID- 9969644 TI - Effect of nucleon correlations on natural orbitals. PMID- 9969645 TI - Effects of Coulomb distortion and final state interaction on the fourth and fifth structure functions. PMID- 9969647 TI - Relativistic mean-field theory and a density-dependent spin-orbit Skyrme force. PMID- 9969646 TI - Boson analyses in the Ge isotopes. PMID- 9969648 TI - Microscopic multicluster description of the neutron-rich helium isotopes. PMID- 9969650 TI - Delta excitations in compressed finite nuclei. PMID- 9969649 TI - Consequences of neutron-proton interactions on backbending. PMID- 9969651 TI - Description of light nuclei with realistic interactions. PMID- 9969652 TI - Full pf shell model study of A=48 nuclei. PMID- 9969653 TI - Sensitivity of polarized neutron-polarized 3He scattering to the excited level structure of 4He. PMID- 9969654 TI - Calculation of the properties of the rotational bands of 155,157Gd. PMID- 9969655 TI - Angular patterns from fragments produced in central heavy-ion collisions. PMID- 9969656 TI - Shell-model study of 40Ca with the 56-MeV (d PMID- 9969657 TI - Measurements and analysis of neutron elastic scattering at 65 MeV. PMID- 9969658 TI - Thermalization related effects in the electrofission of preactinide nuclei. PMID- 9969659 TI - Identification of 4(-) states in the 14C(p,n)14N reaction at 135 MeV. PMID- 9969660 TI - Alpha particle transfer reaction 12C(11B,7Li)16O and lack of evidence for a tetrahedral shape of the 16O nucleus. PMID- 9969661 TI - Energy dependence of 58Ni( pi +, pi -)58Zn double charge exchange. PMID- 9969662 TI - Residue excitation functions from complete fusion of 16O with 197Au and 208Pb. PMID- 9969663 TI - Examination of a "properly deformed folding potential" for the analysis of nuclear inelastic scattering and comparison with true folded potentials. PMID- 9969665 TI - Fluctuations and the canonical model for fragmentation. PMID- 9969664 TI - Cluster-model calculation of quadrupole effects in pion scattering from 7Li. PMID- 9969666 TI - Cascade simulation of a Delta isobar propagating in a nucleus. PMID- 9969667 TI - Extrapolating (e,e'p) to (e,e'). PMID- 9969668 TI - Potentials by inversion of 3He+ alpha phase shifts and bound state energies in 7Be. PMID- 9969669 TI - (p,n) and (3He,t) reactions in coincidence with p pi + in 12C. PMID- 9969670 TI - Optical potential models used in quasielastic 40Ca(e,e'p) calculations. PMID- 9969671 TI - Scaling behavior in first-order quark-hadron phase transition. PMID- 9969672 TI - Analysis of subthreshold antiproton production in p-nucleus and nucleus-nucleus collisions in the relativistic Boltzmann-Uehling-Uhlenbeck approach. PMID- 9969674 TI - Chiral perturbation theory and the SU(2) Nambu-Jona-Lasinio model: A comparison. PMID- 9969673 TI - Gluon production, cooling, and entropy in nuclear collisions. PMID- 9969675 TI - Consistent baryon mapping of quark systems. PMID- 9969677 TI - Off-shell electromagnetic form factors of pions and kaons in chiral perturbation theory. PMID- 9969676 TI - Scalar-pseudoscalar meson masses in nonlocal effective QCD at finite temperature. PMID- 9969678 TI - Equation of state of homogeneous nuclear matter and the symmetry coefficient. PMID- 9969679 TI - Deciphering the CENTAURO puzzle. PMID- 9969680 TI - A K pi =8(-) isomer in 136Sm. PMID- 9969682 TI - Characteristics of the 50V(nth,p)50Ti reaction. PMID- 9969681 TI - Rotational structures in 106Sn: A new form of band termination? PMID- 9969683 TI - Evidence for a spherical subshell at N=164. PMID- 9969684 TI - K dependence in the gamma decay of neutron resonances in 166Ho. PMID- 9969685 TI - Quantum algebraic description of vibrational and transitional nuclear spectra. PMID- 9969687 TI - Nature of the photon correlation function for quark-gluon plasma. PMID- 9969686 TI - Width of the Delta resonance in nuclei. PMID- 9969688 TI - Temperature induced alignment in hot rotating nuclei. PMID- 9969689 TI - Can the Sigma -nn system be bound? PMID- 9969690 TI - Gamow-Teller (p,n) and (n,p) strength in a dressed extended random phase approximation. PMID- 9969691 TI - Comment on "Decays and masses of 162,163Ta and some neighboring nuclides" PMID- 9969692 TI - Erratum: Memory effects in relativistic heavy ion collisions PMID- 9969694 TI - Alleged contra-rotation of neutrons and protons. PMID- 9969693 TI - Simplified alpha +4n model for the 8He nucleus. PMID- 9969695 TI - Bose condensation of nuclei in heavy ion collisions. AB - Using a fully self-consistent quantum statistical model, we demonstrate the possibility of Bose condensation of nuclei in heavy ion collisions. The most favorable conditions of high densities and low temperatures are usually associated with astrophysical processes and may be difficult to achieve in heavy ion collisions. Nonetheless, some suggestions for the possible experimental verification of the existence of this phenomenon are made. PMID- 9969697 TI - Does the presence of 11Li breakup channels reduce the cross section for fusion processes? PMID- 9969696 TI - Reaction cross sections for intermediate energy alpha particles from optical folding-model calculations. PMID- 9969698 TI - Energy dependence of analyzing power Ay and cross section for p+d scattering below 18 MeV. PMID- 9969699 TI - Analyzing power in neutron-deuteron elastic scattering at Elabn=3 MeV. PMID- 9969700 TI - Cross section and analyzing power Ay in the breakup reaction 2H(p PMID- 9969702 TI - Deterministic technique of path summation. PMID- 9969701 TI - The nucleon-nucleon potential in the chromodielectric soliton model: Statics. PMID- 9969703 TI - Two-body correlations from (e,e'd) reactions: 4He(e,e'd)2H as a test case. PMID- 9969704 TI - Coherent state formulation of pion radiation from nucleon-antinucleon annihilation. PMID- 9969705 TI - Reaction pp-->n Delta ++: Observables and model predictions. PMID- 9969707 TI - Neutron-spectroscopic strength in Ru isotopes. PMID- 9969706 TI - Nuclear moments of 143Pr by laser spectroscopy. PMID- 9969708 TI - Lifetimes in 15N from gamma-ray line shapes produced in the 2H(14N,p gamma ) and 14N(thermal n, gamma ) reactions. PMID- 9969709 TI - Deformed intruder band in 112Te: First evidence for rotational behavior in the tellurium isotopes. PMID- 9969710 TI - Deformed rotational bands in the doubly odd nuclei 134Pr and 132Pr. PMID- 9969711 TI - Negative-parity structures and lifetime measurements in 71As. PMID- 9969712 TI - beta + decay and cosmic-ray half-lives of 143Pm and 144Pm. PMID- 9969713 TI - Directional correlation of gamma transitions in 72Ge following the decay of 72Ga. PMID- 9969715 TI - Blocking effect and odd-even differences in the moments of inertia of rare-earth nuclei. PMID- 9969714 TI - Multiple band structures at high angular momentum in 115I: Towards unfavored band termination. PMID- 9969716 TI - General form of hybrid derivative coupling to study dense nuclear matter and its phase transition to quark matter. PMID- 9969717 TI - Liquid-gas phase diagrams and Gibbs free energy per nucleon. PMID- 9969718 TI - New calculations of the parity nonconservation matrix element for the J pi T 0(+)1, 0(-)1 doublet in 14N. PMID- 9969719 TI - Boson mappings of the fermion dynamical symmetry model. PMID- 9969720 TI - Microscopic description of the alpha +16O system in a multicluster model. PMID- 9969721 TI - Octupole excitations in light xenon and barium nuclei. PMID- 9969722 TI - Dependence of nuclear shape transformations on the nuclear volume. PMID- 9969723 TI - Spin-dependent generalized collective model in relation to the j=3/2 interacting boson fermion model. PMID- 9969724 TI - Normal and exotic collective states in the fermion dynamical symmetry model. PMID- 9969725 TI - Model for asymptotic D-state parameters of light nuclei: Application to 4He. PMID- 9969726 TI - Relativistic Hartree calculations of nuclear compressional properties. PMID- 9969728 TI - Excitation of giant resonances in the 40Ca(e,e'n)39Ca reaction. PMID- 9969727 TI - Realistic microscopic level densities for spherical nuclei. PMID- 9969730 TI - Reaction cross sections for 75-190 MeV alpha particles on targets from 12C to 208Pb. PMID- 9969729 TI - Two-proton correlation functions for 36Ar+45Sc at E/A=80 MeV. PMID- 9969731 TI - Complete and incomplete fusion in the 28Si+12C, 13C reactions around 5 MeV/nucleon. PMID- 9969732 TI - Angular correlations of projectilelike and fission fragments in the reaction 16O+238U at 110 MeV. PMID- 9969733 TI - Pion elastic scattering from polarized 13C in the energy region of the P33 resonance. PMID- 9969734 TI - Neutron deformation in 165Ho. PMID- 9969735 TI - Elastic and inelastic scattering of polarized 6Li by 26Mg at 60 MeV. PMID- 9969736 TI - Elastic and inelastic scattering of 16O and 18O ions from 64Zn at energies near the Coulomb barrier. PMID- 9969737 TI - Inclusive systematics for 28Si+28Si reactions between 20 and 35 MeV per nucleon. PMID- 9969739 TI - Effective nucleon-nucleon cross sections based on Skyrme interactions. PMID- 9969738 TI - Two-fragment correlation functions with directional cuts for central 36Ar+197Au collisions at E/A=50 MeV. PMID- 9969740 TI - Does exchange produce L dependence in the optical model potential? PMID- 9969741 TI - Phenomenological model for inelastic scattering of 800 MeV/c pions from nuclei. PMID- 9969742 TI - Projectile fragmentation of halo nuclei in peripheral direct reaction model. PMID- 9969743 TI - Fluctuation dynamics of fragmenting spherical nuclei. PMID- 9969744 TI - Multiple preequilibrium emission in Feshbach-Kerman-Koonin analyses. PMID- 9969745 TI - Excitation functions and asymmetric fission barriers for intermediate mass fragments: 486-730 MeV 86Kr+63Cu. PMID- 9969746 TI - J/ psi suppression in hadron-nucleus collisions. PMID- 9969747 TI - Charged hadron distributions in central and peripheral Si+A collisions at 14.6A GeV/c. PMID- 9969748 TI - Intermittency and correlations in 200 GeV/nucleon S+S and S+Au collisions. PMID- 9969749 TI - Charge-pickup by heavy relativistic nuclei. PMID- 9969751 TI - Intermediate mass fragment emission by 197Au projectiles at relativistic energy in nuclear emulsion. PMID- 9969750 TI - Production of light nuclei in relativistic heavy-ion collisions. PMID- 9969752 TI - Alpha-cluster description of excitation energies in 12C(12C,3 alpha)X at 2.1A GeV. AB - An alpha-cluster expansion of the Glauber multiple scattering [correction of scatteirng] series is used to calculate the energy transfer spectrum to the 12C projectile in the 12C(12C,3 alpha)X reaction at 2.1A GeV. Cluster-abrasion response functions are defined in terms of alpha-cluster wave function and the collision dynamics appropriate for heavy-ion reactions. Comparisons are made to recent quasiexclusive experimental data with good agreement found. Calculations indicate that substructures in a 12C projectile are likely to be true spectators in fragmentation, however, with virtual states of excitation in the projectile ground state making a significant contribution to the fragmentation cross section. PMID- 9969753 TI - Temperature of protons in inelastic (d, alpha, C)+(C, Ta) collisions at 4.2A GeV/c. PMID- 9969754 TI - Mott scattering as a probe of long range QCD effects. PMID- 9969755 TI - Coalescence model for deuterons and antideuterons in relativistic heavy-ion collisions. PMID- 9969756 TI - Relation of QCD sum rules in matter and the nuclear many-body problem. PMID- 9969757 TI - Dynamical color correlations in a SU(2)c quark exchange model of nuclear matter. PMID- 9969758 TI - Shadowing, binding, and off-shell effects in nuclear deep-inelastic scattering. PMID- 9969759 TI - Results of a search for double positron decay and electron-positron conversion of 78Kr. PMID- 9969760 TI - Parity-violating asymmetry in elastic e PMID- 9969761 TI - Beta decay properties of 67,68Se and the astrophysical rp-process path. PMID- 9969762 TI - Reaction rate for 31S(p, gamma )32Cl and its influence on the SiP cycle in hot stellar hydrogen burning. PMID- 9969763 TI - Constraints on the low-energy E1 cross section of 12C( alpha, gamma )16O from the beta -delayed alpha spectrum of 16N. PMID- 9969765 TI - Lifetimes of the excited states of 90,92Mo. PMID- 9969764 TI - Double analog state in odd-A nuclei. PMID- 9969766 TI - Superdeformation in the Pb nuclei and the evolution of the dynamic moments of inertia. PMID- 9969767 TI - 4He induced 6Li--> alpha +d target breakup in the region of small relative fragment energies. PMID- 9969768 TI - Elastic scattering threshold anomaly and near-barrier heavy-ion fusion. PMID- 9969769 TI - van der Waals forces in nonrelativistic quark models of the NN interaction. PMID- 9969771 TI - Single particle energies in 17O with the Bonn potential. PMID- 9969770 TI - pi 0 electromagnetic self-energy and its implications for incorporating electromagnetism in few-body systems. PMID- 9969773 TI - Nuclear shadowing in a parton recombination model: Q2 variation. PMID- 9969772 TI - Comparison of the relativistic Hartree-Fock approximation and its semiclassical expansion. PMID- 9969774 TI - Comment on "Masses of stable xenon isotopes: Check for internal consistency via ion cyclotron resonance mass spectrometry" PMID- 9969776 TI - Erratum: From nuclear matter to finite nuclei. II. Relativistic theories for finite nuclei PMID- 9969775 TI - Differences between the deformed-potential and folding-model descriptions of inelastic nuclear scattering. PMID- 9969777 TI - Fragment mass dependence of pT at GeV per nucleon energies. PMID- 9969779 TI - Evidence for octupole correlations at high spins in neutron-deficient 110Te. PMID- 9969778 TI - Pseudospin flip in doubly decoupled structures and identical bands. PMID- 9969780 TI - Total d+d--> alpha + eta cross sections near threshold. PMID- 9969781 TI - Multiple hadron production by 14.5 GeV electron and positron scattering from nuclear targets. PMID- 9969782 TI - Measurement of the neutron magnetic form factor from inclusive quasielastic scattering of polarized electrons from polarized 3He. PMID- 9969784 TI - Configuration of the two-neutron halo of 11Li and Gamow-Teller transition. PMID- 9969783 TI - Three-body model for 11Li with separable potentials. PMID- 9969785 TI - Hadron widths in mixed-phase matter. PMID- 9969786 TI - Heat capacity of a Fermi system and multifragmentation of nuclei. PMID- 9969788 TI - Hermitian boson mapping and finite truncation. PMID- 9969787 TI - Transfer and fusion reactions of unstable nuclei. PMID- 9969789 TI - Off-shell effects for the reaction pp--> pi d at high energies. PMID- 9969790 TI - Local 4He-p potentials from resonating-group method phase shifts. PMID- 9969792 TI - Test of predicted gamma stability at spins above 8 PMID- 9969791 TI - Measurement of the half-life of the first excited state of 205Pb. PMID- 9969793 TI - Gaps in the yrast level structure of the N=50 isotones 93Tc, 94Ru, and 95Rh at high angular momentum. PMID- 9969795 TI - (sd)2 states in 12Be. PMID- 9969794 TI - Spectroscopy of 95Ru at high spins. PMID- 9969796 TI - High-K bands in the 166Yb region. PMID- 9969797 TI - Short lifetimes in 28Al. PMID- 9969798 TI - Semimicroscopic description of the odd-A Te isotopes. PMID- 9969799 TI - Microscopic investigation of nuclear structure with dynamic Bose-Fermi symmetry. PMID- 9969800 TI - Reduction of nuclear moment of inertia due to pairing interaction. PMID- 9969801 TI - Structure of neutron-deficient Pt, Hg, and Pb isotopes. PMID- 9969802 TI - Microscopic energy correction to the ground states of some rare-earth nuclei. PMID- 9969803 TI - Nuclear matter with scalar-vector interactions. PMID- 9969804 TI - Effect of pion external distortion on low-energy pion double charge exchange. PMID- 9969806 TI - Generator coordinate calculations for breathing-mode giant monopole resonance in the relativistic mean-field theory. PMID- 9969805 TI - Relativistic investigation of nuclear surface properties. PMID- 9969807 TI - Theory of parity violation in compound nuclear states: One particle aspects. PMID- 9969808 TI - sp(6) PMID- 9969809 TI - 6Li inelastic form factors in a cluster model. PMID- 9969810 TI - Escape and spreading properties of charge-exchange resonances in 208Bi. PMID- 9969811 TI - Final state interactions and relativistic effects in y scaling. PMID- 9969812 TI - Mean field description of the ground state of many boson systems relevant to nuclei. PMID- 9969813 TI - Isovector giant quadrupole resonance observed in 89Y(p PMID- 9969814 TI - Structural connection of highly deformed shape isomeric states in 28Si, 24Mg, and 20Ne by alpha-alpha coincidence studies in 12C(16O, alpha )24Mg*--> alpha +20Ne* PMID- 9969815 TI - Direct capture in the 3(+) resonance of 2H( alpha, gamma )6Li. PMID- 9969816 TI - Transfer reactions in 32S+92,98,100Mo and 93Nb at near barrier energies. PMID- 9969818 TI - Phenomenological pp-->d pi + model of A(p PMID- 9969817 TI - Exclusive pion production from few nucleon systems in the region of the Delta 1232 resonance. PMID- 9969819 TI - Scalar and vector meson production in (K-,K+) reactions on nuclei. PMID- 9969821 TI - Preequilibrium alpha emission in the exciton model. PMID- 9969820 TI - "Super-radiant" states in intermediate energy nuclear physics. PMID- 9969823 TI - Nuclear transparency in (e,e'p) reactions. PMID- 9969822 TI - Momentum-dependent nuclear mean fields and collective flow in heavy-ion collisions. PMID- 9969824 TI - Dynamical behavior and energy dissipation of a classical particle in harmonic plus-Legendre potential. PMID- 9969825 TI - Longitudinal and transverse spin response of C12 in the Delta resonance region. PMID- 9969826 TI - Schrodinger optical-potential calculation of 500 MeV polarized proton scattering from polarized 13C. PMID- 9969828 TI - Hydrodynamical assessment of 200A GeV collisions. PMID- 9969827 TI - Residue temperatures in intermediate energy nucleus-nucleus collisions. PMID- 9969830 TI - Photons from axial-vector radiative decay in a hadron gas. PMID- 9969829 TI - Strangeness flow difference in nuclear collisions at 15A and 200A GeV. PMID- 9969832 TI - Capture of solar and higher-energy neutrinos by 127I. PMID- 9969831 TI - Resonant scattering of isobaric 19Ne and 19F beams on an H target. PMID- 9969833 TI - Neutron multiplicities and energy sharing in the inelastic collisions of 32S on 64Ni at E/A=4.9 MeV. PMID- 9969834 TI - Very weak gamma transitions in the epsilon / beta + decay of 68Ga. PMID- 9969835 TI - Signature of non-compound-nucleus fission at sub-barrier energies. PMID- 9969837 TI - Population of T< states in pion double charge exchange at T pi =292 MeV. PMID- 9969836 TI - Perturbative description of the temperature dependence of the resonance width. PMID- 9969839 TI - Subthreshold response function in the Delta -resonance region. PMID- 9969838 TI - Antiproton production in Ni+Ni collisions at 1.85 GeV/nucleon. PMID- 9969841 TI - Spectral asymmetries in nucleon sum rules at finite density. PMID- 9969840 TI - Strength of the rho meson coupling to nucleons. PMID- 9969842 TI - Alpha particle emission as a probe of the level density in highly excited A~200 nuclei. PMID- 9969844 TI - Lifetimes of levels in 20F. PMID- 9969843 TI - Excitations in doubly-magic superdeformed 194Pb. PMID- 9969845 TI - Simulations of collisions between nuclei at intermediate energy using the Boltzmann-Uehling-Uhlenbeck equation with neutron skin producing potentials. PMID- 9969846 TI - Coulomb breakup mechanism of neutron drip-line nuclei. PMID- 9969847 TI - New interpretation of the lowest K=0 collective excitation of deformed nuclei as a phonon excitation of the gamma band. PMID- 9969848 TI - Exclusive pion radiative capture from nuclei in the Delta region. PMID- 9969849 TI - Neutron star properties and the relativistic equation of state of asymmetric nuclear matter. PMID- 9969850 TI - Shell model on a random Gaussian basis. PMID- 9969851 TI - Theoretical interpretation of the NE18 experiment on nuclear transparency in A(e,e'p) scattering. PMID- 9969852 TI - Multinucleon effects in muon capture on 3He at high energy transfer. PMID- 9969853 TI - Classical and quantum coherent state description of NN-bar annihilation at rest in the Skyrme model with omega mesons. PMID- 9969854 TI - Analysis of pi d elastic scattering data to 500 MeV. PMID- 9969856 TI - Role of the g9/2 neutron orbital in the structure of 65Zn. PMID- 9969855 TI - Observation of beta-delayed proton emission from 24Al. PMID- 9969858 TI - Level scheme of 114Sb from the (p,n gamma ) reaction. PMID- 9969857 TI - Rotational bands near the Z=50 closed shell: 51111Sb. PMID- 9969859 TI - High-lying three-quasiparticle bands and signature splitting in 81Rb. PMID- 9969860 TI - Functional approach to the electromagnetic response function: The longitudinal channel. PMID- 9969861 TI - Particle-rotor model analysis of low-spin identical bands in neighboring odd-A and even-even nuclei. PMID- 9969863 TI - Dependence of the Landau parameters on the single particle potential. PMID- 9969862 TI - q deformations in the interacting boson model for nuclei. PMID- 9969864 TI - Excited bands of 168Yb in an angular momentum projected theory. PMID- 9969866 TI - Determination of nuclear level densities from experimental information. PMID- 9969865 TI - Signature splitting in nuclear rotational bands: Neutron i13/2 systematics. PMID- 9969867 TI - Can we do without the Majorana term in the effective nuclear interaction? PMID- 9969868 TI - Shape and superdeformed structure in Hg isotopes in relativistic mean field model. PMID- 9969869 TI - Comparison between two variational approaches for non-Hermitian boson Hamiltonians. PMID- 9969870 TI - Generator coordinate method calculations for 4He and 16O nuclei. PMID- 9969871 TI - Explosive multifragmentation in the 32S+27Al reaction at 37.5 MeV/nucleon. PMID- 9969872 TI - 207,208Pb(n,xn gamma ) reactions for neutron energies from 3 to 200 MeV. PMID- 9969873 TI - Experimental observation of long delay times in the reaction induced by oxygen ions on nickel crystals. PMID- 9969874 TI - Deexcitation of primary projectile-like fragments in the reaction 40Ca+natCu at 35 MeV/nucleon: Comparison with sequential binary decay and percolation models. PMID- 9969875 TI - Energy dependence of the 12C(p,p')12C* reaction from 200 to 800 MeV. PMID- 9969877 TI - Elastic scattering cross sections of 11.4 MeV photons from 206,207,208Pb, 209Bi, and 181Ta. PMID- 9969876 TI - "Preresidue" light charged particles from 28Si+165Ho, 16O+197Au, and 16O+208Pb fusion. PMID- 9969878 TI - Cluster-folding analysis of 6Li PMID- 9969879 TI - Violent collisions and multifragment final states in the 40Ca+40Ca reaction at 35 MeV/nucleon. PMID- 9969880 TI - Breakup-fusion analyses of the 240 MeV 40Ca(3He,d) and 40Ca(3He,dp) reactions. PMID- 9969881 TI - Projectile mass dependence for the interaction of copper with 14N, 16O, and 22Ne at ~540 MeV total projectile kinetic energy. PMID- 9969882 TI - Complete expansion calculation of the Glauber amplitude for alpha -12C scattering at high energy. PMID- 9969883 TI - Light nuclei production in fusion of heavy ions. PMID- 9969884 TI - Coupled channels analysis of 19F+12C elastic and inelastic scattering using a cluster-folding interaction. PMID- 9969885 TI - Fully isotopic model of fragmentation. PMID- 9969887 TI - One-nucleon transfer between heavy ions at intermediate energies. PMID- 9969886 TI - Observable consequences of chemical equilibration in energetic heavy ion collisions. PMID- 9969888 TI - Coulomb dissociation of 8B into 7Be+p: Effects of multiphoton exchange. PMID- 9969889 TI - Mechanism of 20Ne(t,p) and nuclear structure of 22Ne. PMID- 9969890 TI - Energy storage in intermediate energy heavy-ion collisions. PMID- 9969891 TI - Nonlocal effects in the nucleus-nucleus fusion cross section. PMID- 9969892 TI - Near-threshold K+ production in heavy-ion collisions. PMID- 9969893 TI - Estimates of antiproton production and annihilation in relativistic nucleus nucleus collisions. PMID- 9969894 TI - Collective global dynamics in Au+Au collisions at the BNL AGS. PMID- 9969895 TI - High pt pions as probes of the dense phase of relativistic heavy ion collisions. PMID- 9969897 TI - Pitfalls in looking for color transparency at intermediate energies. PMID- 9969896 TI - Many-body currents and the strange-quark content of 4He. PMID- 9969898 TI - Depopulation of 180Tam by Coulomb excitation and possible astrophysical consequences. PMID- 9969899 TI - 3H( alpha, gamma )7Li reaction at low energies. PMID- 9969900 TI - Identification of new nuclei near the proton drip line. PMID- 9969902 TI - Statistical model of three nucleon pion absorption. PMID- 9969901 TI - Width of the 3841-keV level in 17O. PMID- 9969904 TI - Electrical chemical potential and pi -- pi + asymmetry in heavy-ion collisions. PMID- 9969903 TI - Convergence of triton asymptotic wave function for hyperspherical harmonics expansion with two nucleon Reid soft core potential. PMID- 9969905 TI - Constraint on time-reversal tests in fully chaotic nuclear systems. PMID- 9969907 TI - Low-energy 12C( alpha, gamma )16O cross section from K-matrix fits. PMID- 9969906 TI - Multichannel dynamical symmetry and heavy ion resonances. PMID- 9969908 TI - Can one simultaneously describe the deuteron properties and the nucleon-nucleon phase shifts in the quark cluster model? PMID- 9969909 TI - Electric form factor of the neutron from the 2H(e PMID- 9969910 TI - Low-lying structure of the neutron-deficient isotope 202Rn. PMID- 9969911 TI - Weak coupling in 143Nd. PMID- 9969912 TI - Quasielastic 40Ca(e,e') reaction in the transverse channel: Nuclear structure effects. PMID- 9969913 TI - Multiphonon structure of gamma -unstable or O(6) nuclei. PMID- 9969914 TI - Short range interaction of nucleons inside the nucleus via 4He(e,e'p)R reactions. PMID- 9969915 TI - Electron-capture delayed fission properties of 228Np. PMID- 9969916 TI - High-spin collective structures in doubly-odd 114Sb. PMID- 9969917 TI - Quadrupole-quadrupole plus pairing interaction application to transition charge density calculations in some even-even palladium nuclei. PMID- 9969918 TI - Two nucleon induced Lambda decay and the neutron to proton induced ratio. PMID- 9969919 TI - q-deformed pairing vibrations. PMID- 9969920 TI - Evidence for gamma vibrations and shape evolutions through the transitional 184,186,188,190Hg nuclei. PMID- 9969921 TI - Nolen-Schiffer anomaly of mirror nuclei and charge symmetry breaking in nuclear interactions. PMID- 9969922 TI - Varied signature splitting phenomena in odd proton nuclei. PMID- 9969923 TI - Nuclear magnetic quadrupole moments in the single-particle approximation. PMID- 9969925 TI - Three-body halos. II. From two- to three-body asymptotics. PMID- 9969924 TI - Towards a satisfactory microscopic description of 21+ g factors. PMID- 9969926 TI - In-medium scaling law and electron scattering from high-spin states in 208Pb. PMID- 9969927 TI - Parity mixed doublets in A=36 nuclei. PMID- 9969929 TI - Excitation functions of proton and deuteron induced reactions on iron and alpha particle induced reactions on manganese in the energy region up to 25 MeV. PMID- 9969928 TI - Production cross sections and the particle stability of proton-rich nuclei from 58Ni fragmentation. PMID- 9969930 TI - Isotropic fragmentation distribution of 129Xe on 90Zr and 197Au targets at intermediate energy. PMID- 9969931 TI - Time scale for multifragmentation in intermediate energy heavy-ion reactions. PMID- 9969932 TI - (p,n) quasifree excitations in p-shell nuclei at 186 MeV. PMID- 9969933 TI - Quasifree knockout in 9Be( alpha,2 alpha )5He at an incident energy of 197 MeV. PMID- 9969935 TI - Atomic energy loss corrections for (p,n) and (p, gamma ) nuclear reaction energies. PMID- 9969934 TI - Role of the supersymmetric semiclassical approach in barrier penetration and heavy-ion fusion. PMID- 9969936 TI - Approach for calculating multistep direct reactions of continuum and discrete levels. PMID- 9969937 TI - Deuteron effects in nucleon-nucleus scattering at intermediate energies. PMID- 9969939 TI - Anisotropic alpha decay from oriented odd-mass isotopes of some light actinides. PMID- 9969938 TI - Continuum angular distributions in preequilibrium nuclear reactions: Physical basis for Kalbach systematics. PMID- 9969940 TI - Multifractal analysis of 197Au-emulsion collisions at 10.6A GeV. PMID- 9969942 TI - Multiple scattering effects on boson interferometry in high energy heavy-ion collisions. PMID- 9969941 TI - Cluster growth in two-dimensional quark-hadron phase transition. PMID- 9969943 TI - Heavy-resonance production in high-energy nuclear collisions. PMID- 9969944 TI - Relativistic treatment of spin-transfer observables in quasielastic (p PMID- 9969945 TI - Structure function of off-mass-shell pions and the calculation of the Sullivan process. PMID- 9969946 TI - Relativistic meson spectroscopy in momentum space. PMID- 9969947 TI - Muon capture, continuum random phase approximation, and in-medium renormalization of the axial-vector coupling constant. PMID- 9969949 TI - Lifetimes of low-spin states in the superdeformed band of 192Hg. PMID- 9969948 TI - Stellar neutron capture cross sections of the Ba isotopes. PMID- 9969950 TI - Successful description of elastic scattering of 3He particles at 150 MeV/nucleon with the single folding potential model. PMID- 9969951 TI - Onset of collectivity in the ground-state band of 50Cr. PMID- 9969953 TI - Thermal equilibrium of the nuclear system in the 40Ca(35 MeV/nucleon)+40Ca reaction. PMID- 9969952 TI - Measurement of the Q beta value for the beta decay of mass separated 84As-->84Se. PMID- 9969955 TI - Optical model analysis of 12Be and 14Be quasielastic scattering on a 12C target at 56 MeV per nucleon. PMID- 9969954 TI - Origin of empirical threshold for dissipative fission. PMID- 9969956 TI - Relativistic impulse approximation treatment of the elastic scattering of 400 MeV pi +/- on 28Si. PMID- 9969958 TI - Alpha-cluster states of 212Po in a realistic potential model. PMID- 9969957 TI - Spin structure of the deuteron from the d PMID- 9969959 TI - Microscopic analysis of the 3He(3He,2p)4He and 3H(3H,2n)4He reactions in a three cluster model. PMID- 9969960 TI - Observables for polarized neutrons transmitted through polarized targets. PMID- 9969961 TI - Erratum: Color transparency and Dirac-based spin effects in (e,e'p) reactions PMID- 9969962 TI - Proton configurations and pairing correlations at the N=80 superdeformed shell closure: Study of 145Tb. PMID- 9969963 TI - Measurements of the (e,e'p pi -) reaction on nuclei in the nucleon resonance region. PMID- 9969964 TI - Gamow-Teller strength in the region of 100Sn. PMID- 9969965 TI - Truncation method for shell model calculations. PMID- 9969967 TI - Determination of the asymptotic D- to S-state ratio of the triton from sub Coulomb (d PMID- 9969966 TI - 1H(d,2p)n reaction at 2 GeV deuteron energy. PMID- 9969968 TI - Two-body pion absorption on 3He at threshold. PMID- 9969969 TI - Paris NN-bar potential and recent proton-antiproton low energy data. PMID- 9969970 TI - Updated analysis of NN elastic scattering data to 1.6 GeV. PMID- 9969972 TI - How important is the three-nucleon force? PMID- 9969971 TI - Neutron-proton charge exchange. PMID- 9969973 TI - Theory of coupled pi -trinucleon systems. PMID- 9969975 TI - Neutron resonance spectroscopy on 113Cd to En=15 keV. PMID- 9969974 TI - Alpha decay of 186Pb and 184Hg: The influence of mixing of 0(+) states on alpha decay transition probabilities. PMID- 9969976 TI - Shape changes in 79Kr. PMID- 9969977 TI - Simple phenomenology for the ground-state bands of even-even nuclei. PMID- 9969978 TI - Collective isospin excitations in nuclear matter droplets. PMID- 9969979 TI - Study of a soft quadrupole excitation in the nucleus 11Li: A phase space model of neutron halo nuclei. PMID- 9969980 TI - Study of neutron and proton distributions in Ca, Sn, and Ba isotopes by polarized electron scattering. PMID- 9969982 TI - Staggering of the nuclear charge radii in a superfluid model with good particle number. PMID- 9969981 TI - Relativistically generated asymmetry in the missing-momentum distribution from the (e,e'p) reaction. PMID- 9969983 TI - Large-space shell-model calculations for light nuclei. PMID- 9969984 TI - Nuclear level densities and thermal properties for fixed spin in microscopic treatments. PMID- 9969985 TI - Mean-field description of ground-state properties of drip-line nuclei: Shell correction method. PMID- 9969986 TI - Practical formulation of the extended Wick's theorem and the Onishi formula. PMID- 9969987 TI - Effect of nucleon correlation in the 0 nu beta beta decay of 76Ge and 82Se. PMID- 9969988 TI - Coherence of nucleonic motion in superdeformed nuclei: Towards an understanding of identical bands. PMID- 9969989 TI - Hybrid symmetry-conserving variational procedure for nuclear structure calculations. PMID- 9969990 TI - Bertlmann-Martin inequalities in hypernuclei. PMID- 9969991 TI - Angular-distribution measurements for 12C(12C,12C PMID- 9969993 TI - Isospin dependence of double analog cross sections at T pi =400-500 MeV. PMID- 9969992 TI - Analyzing powers for elastic and inelastic scattering of polarized 6Li from 12C at 30 MeV. PMID- 9969994 TI - Sensitivity to the impact parameter of the multiparticle decay at intermediate energy. PMID- 9969995 TI - Experimental survey of the (d PMID- 9969996 TI - Effect of memory time on the agitation of unstable modes in nuclear matter. PMID- 9969997 TI - Salient features of scattering amplitudes in intermediate energy nucleon-nucleus scattering. PMID- 9969998 TI - Scaling of multiplicity fluctuations in 800 GeV proton-nucleus interactions. PMID- 9970000 TI - Photopion p-wave multipoles near threshold from 12C( gamma, pi 0) and 1H( gamma, pi 0). PMID- 9969999 TI - Unified theory for fission path and high angular momentum phenomena of nuclei. PMID- 9970001 TI - Validity of local density prescriptions for microscopic calculations of proton nucleus elastic scattering. PMID- 9970002 TI - Many-body effects in 16O(e,e'p). PMID- 9970003 TI - Orthogonality effects in the coherent nuclear production of jets. PMID- 9970004 TI - Power moments and scaling properties of nuclear emulsion data. PMID- 9970006 TI - Coulomb plus nuclear scattering in momentum space for coupled angular momentum states. PMID- 9970005 TI - Second order effects in the algebraic potential for heavy-ion systems near the Coulomb barrier. PMID- 9970007 TI - Centrality dependence of longitudinal and transverse baryon distributions in ultrarelativistic nuclear collisions. PMID- 9970008 TI - Photon interferometry of quark-gluon dynamics reexamined. PMID- 9970009 TI - Secondary phi meson peak as an indicator of a QCD phase transition in ultrarelativistic heavy-ion collisions. PMID- 9970010 TI - Large time-scale fluctuations of the quark condensate at high temperature. PMID- 9970011 TI - Pion interferometry with pion-source-medium interactions. PMID- 9970012 TI - Elimination of the Landau ghost from chiral solitons. PMID- 9970013 TI - Thermodynamics of the QCD1+1 nonrelativistic baryon gas. PMID- 9970014 TI - Strange vector form factors of the nucleon. PMID- 9970015 TI - Random-sign observables nonvanishing upon averaging: Enhancement of weak perturbations and parity nonconservation in compound nuclei. PMID- 9970017 TI - Effects of symmetry energy on the direct URCA process in the kaon condensed phase. PMID- 9970016 TI - Spontaneous breakdown of isospin symmetry in nuclei and isobaric analog states. PMID- 9970018 TI - (EC+ beta +) decay of 157Yb. PMID- 9970019 TI - Saturation effects in the 10B+11B reaction at E/A=11 MeV. PMID- 9970020 TI - 15N cluster states in triton transfer and their alpha decay. PMID- 9970021 TI - Octupole correlations in the odd-Z nuclei 148-151Eu. PMID- 9970022 TI - Analytic extension of the nuclear algebraic potential. PMID- 9970023 TI - Simultaneous projectile-target excitation in heavy ion collisions. PMID- 9970024 TI - Isovector meson contribution in the relativistic Hartree-Fock approach for finite nuclei. PMID- 9970025 TI - Comment on "Elastic scattering of 58Ni+27Al at near-barrier energies" PMID- 9970026 TI - Erratum: 16O(02+)+ alpha ] parentage of continuum levels in 20Ne PMID- 9970027 TI - Strongly coupled enhanced-deformation band in 131Pr. PMID- 9970029 TI - Momentum dependent Vlasov-Uehling-Uhlenbeck calculation of mass dependence of the flow disappearance in heavy-ion collisions. PMID- 9970028 TI - Two-neutrino double-beta decay matrix elements for ground and excited states of 76Ge and 82Se nuclei. PMID- 9970030 TI - Decay properties of giant multipole resonances: Hybrid model for channel types competition. PMID- 9970031 TI - Pygmy dipole resonances in the calcium isotopes. PMID- 9970032 TI - Effects of N*(1440) resonance on particle production in heavy-ion collisions at subthreshold energies. PMID- 9970033 TI - Size and excitation energy distributions of projectile spectators in multifragmentation data. PMID- 9970034 TI - Theoretical prevision for the low-energy 3S1-3D1 mixing parameters. PMID- 9970036 TI - Light front dynamics of one boson exchange models of the two-nucleon system. PMID- 9970035 TI - Measurement of gamma PMID- 9970037 TI - Accurate nucleon-nucleon potential with charge-independence breaking. PMID- 9970038 TI - Spin-dependent structure functions of nuclei in the meson-nucleon theory. PMID- 9970039 TI - Relativistic effect on low-energy nucleon-deuteron scattering. PMID- 9970040 TI - In-beam gamma -ray spectroscopy above 100Sn using the new technique of recoil decay tagging. PMID- 9970042 TI - Study of low-spin states in 122Cd. PMID- 9970041 TI - Pion inelastic scattering to low-lying positive-parity states in 20Ne. PMID- 9970043 TI - Study of 110Cd from the 110Inm beta decay. PMID- 9970045 TI - alpha -decay rates for 181-186Au and 181-185Pt isotopes. PMID- 9970044 TI - Collectivity of dipole bands in 196Pb. PMID- 9970046 TI - Interacting boson approximation studies of the negative parity states of 172 180Os isotopes. PMID- 9970047 TI - Staggering in low-spin nuclear spectra of gamma -soft or triaxial nuclei. PMID- 9970048 TI - Pairing multiplets in nuclei with O(6) dynamic symmetry. PMID- 9970050 TI - Behavior of negative parity spin modes as a function of the strength of the tensor interaction: Shell model vs one particle one hole (or random-phase approximation). PMID- 9970049 TI - Alpha-chain states in 12C. PMID- 9970051 TI - Mass resolved angular distribution in 10B, 12C, and 16O induced fission of 232Th. PMID- 9970052 TI - Excitation-energy partition in quasielastic transfer reactions at near barrier energies. PMID- 9970053 TI - Elastic scattering of 10 MeV 6He from 12C, natNi, and 197Au. PMID- 9970054 TI - Effects of triple scattering in heavy-ion reactions. PMID- 9970055 TI - Dynamical norm method for nonadiabatic macroscopic quantum tunneling. PMID- 9970056 TI - Dynamics of fragment formation in the nuclear spinodal region. PMID- 9970057 TI - Higher-order corrections to the eikonal phase shifts for heavy-ion elastic collision. PMID- 9970058 TI - Limitations to presaddle neutron emission from fission-fragment charge distributions. PMID- 9970059 TI - Dielectron production in proton-proton and proton-deuteron collisions at 1-2 GeV. PMID- 9970060 TI - Pion cloud contribution to K+-nucleus scattering. PMID- 9970061 TI - Microscopic abrasion-ablation approximation to projectile fragmentation. PMID- 9970062 TI - Spin-isospin response functions and the effects of the Delta -hole configurations in finite nuclei. PMID- 9970063 TI - Nucleon resonances and pion-nucleon interaction in nuclear matter above the Delta resonance energy. PMID- 9970064 TI - Flow of nucleons and fragments in 40Ar+27Al collisions studied with antisymmetrized molecular dynamics. PMID- 9970065 TI - Comparison of experimental data to the relativistic quantum molecular dynamics model for Si+Au collisions at 14.6A GeV/c. PMID- 9970067 TI - Source dimensions in ultrarelativistic heavy-ion collisions. PMID- 9970066 TI - Rapidity distribution of photons emitted from a hadronizing quark-gluon plasma. PMID- 9970068 TI - Collapse of flux tubes. PMID- 9970069 TI - QCD sum rules for Sigma hyperons in nuclear matter. PMID- 9970070 TI - Compton scattering by a pion and off-shell effects. PMID- 9970071 TI - Quark cluster signatures in deuteron electromagnetic interactions. PMID- 9970072 TI - Neutrinoless double beta decay of 48Ca. PMID- 9970074 TI - Bridging the waiting points: The role of two-proton capture reactions in the rp process. PMID- 9970073 TI - Stellar cross sections for 33S(n, alpha )30Si, 36Cl(n,p)36S, and 36Cl(n, alpha )33P and the origin of 36S. PMID- 9970076 TI - Importance of nucleon recoil in weak decay of hypernuclei. PMID- 9970075 TI - Prolate-oblate band mixing and new bands in 182Hg. PMID- 9970078 TI - Symmetry analysis of many-body wave functions, with applications to the nuclear shell model. PMID- 9970077 TI - Empirical fit to the nucleon electromagnetic form factors. PMID- 9970079 TI - Neutron removal in peripheral relativistic heavy-ion collisions. PMID- 9970081 TI - Statistical nucleon correlation coefficients for the 3H and 3He nuclei. PMID- 9970080 TI - Experimental bounds for spin transfer observables in pi d elastic scattering. PMID- 9970083 TI - Further study of pi -12C elastic scattering at 800 MeV/c. PMID- 9970082 TI - Deuteron nuclear polarization shifts with realistic potentials. PMID- 9970084 TI - C4 symmetry effects in nuclear rotational motion. PMID- 9970085 TI - Exchange process amplitudes in coherent pion production. PMID- 9970086 TI - Baryon resonances: A primary rho -->l+l- source in p+p and p+d at 4.9 GeV. PMID- 9970087 TI - pi -N correlations probe the nuclear equation of state in relativistic heavy-ion collisions. PMID- 9970088 TI - Negative pion absorption at rest in 3He. PMID- 9970090 TI - Structure of the p-h nucleus 132Sb. PMID- 9970089 TI - Dipole strengths in 11Be from electroproduction of charged pions. PMID- 9970091 TI - Lifetime of the 21+ state in 154Gd and deduction of the alpha coefficient for the 21+-->01+ transition. PMID- 9970093 TI - Isomeric transitions in 69Se and the spin of the ground state. PMID- 9970092 TI - Magnetic moment measurements in 86Zr. PMID- 9970094 TI - Fragmentation and splitting of Gamow-Teller resonances in Sn(3He,t)Sb charge exchange reactions, A=112-124. PMID- 9970095 TI - Signatures of Lambda - Sigma mixing in the magnetic moments of hypernuclei. PMID- 9970097 TI - Description of low-lying vibrational and two-quasiparticle states in 166Er. PMID- 9970096 TI - New symmetry in many-body effective Hamiltonians: An example of rotating nuclei. PMID- 9970098 TI - Systematics of alpha-cluster states above double shell closures. PMID- 9970100 TI - Structure of the even-even Kr isotopes within the interacting boson model. PMID- 9970099 TI - Vector resonances and electromagnetic nucleon structure. PMID- 9970101 TI - Fast method for obtaining finite range corrected potential energy surfaces. PMID- 9970102 TI - Structure study of 42Ca by alpha +38Ar cluster model: Coexistence of alpha particle clustering and shell structure. PMID- 9970103 TI - 12C emission from 114Ba and nuclear properties. PMID- 9970104 TI - Mean square radii of nuclei calculated with the Woods-Saxon potential. PMID- 9970105 TI - New expansion technique for spectral distribution calculations. PMID- 9970106 TI - Non-Markovian approach to the damping of giant monopole resonances in nuclei. PMID- 9970107 TI - Extraction of nuclear level densities from neutron spectra emitted in proton induced reactions on lead isotopes and Bi. PMID- 9970108 TI - Fusion-fission cross sections for 32S+138Ba and 48Ti+122Sn at near-barrier energies. PMID- 9970109 TI - Search for entrance channel effects in sub-barrier fusion reactions. PMID- 9970111 TI - Analyzing powers for the 12C(6Li PMID- 9970110 TI - Isospin character of transitions to the 21+ and 31- states of 90,92,94,96Zr. PMID- 9970112 TI - Nonanalog 40,44Ca( pi +, pi -)40,44Ti(g.s.) reactions at low energy. PMID- 9970113 TI - Quasielastic K+ scattering. PMID- 9970114 TI - Cold multinucleon transfer and formation of a dinuclear complex. PMID- 9970115 TI - 12C+12C "6 alpha -chain state" resonance. PMID- 9970117 TI - Onset of multifragmentation in intermediate energy light asymmetrical collisions. PMID- 9970116 TI - Angular correlations and widths for alpha-particle decay in the reaction 7Li(12C,15N*--> alpha +11Bg.s.) alpha. PMID- 9970118 TI - Effects of compression and collective expansion on particle emission from central heavy-ion reactions. PMID- 9970120 TI - Coupled-channels analyses of scattering and fusion cross sections of 16O+152,154Sm, 186W systems at sub- and near-Coulomb barrier energies. PMID- 9970119 TI - Nuclear photofissility at intermediate and high energies. PMID- 9970121 TI - Distorted-wave impulse approximation calculations of proton polarization following pi + absorption in nuclei. PMID- 9970123 TI - Relativistic models for quasielastic (e,e') at large momentum transfers. PMID- 9970122 TI - Quasielastic knockout of clusters from p-shell nuclei by 1 GeV protons: Spectroscopic amplitudes of virtually excited clusters and the eikonal approximation. PMID- 9970124 TI - Angular distributions following three-nucleon pion absorption. PMID- 9970125 TI - Temperatures of fragment kinetic energy spectra. PMID- 9970126 TI - Comparison of K+ and e- quasielastic scattering. PMID- 9970127 TI - High energy single particle states in the continuum. PMID- 9970128 TI - Ambiguities in strong absorptionlike S functions and in the corresponding potentials for heavy-ion collisions. PMID- 9970130 TI - Target dependence of K+-nucleus total cross sections. PMID- 9970129 TI - Influence of resonant channels on subbarrier heavy-ion fusion. PMID- 9970131 TI - Electromagnetic dissociation of relativistic 28Si. PMID- 9970132 TI - String fusion and multinucleon interactions in nuclei. PMID- 9970133 TI - Probing short-range nucleon correlations in high-energy hard quasielastic pd reactions. PMID- 9970134 TI - Nucleation of quark-gluon plasma from hadronic matter. PMID- 9970135 TI - Deduction of the in-medium gluon distribution from photon-gluon fusion processes in peripheral ultrarelativistic heavy-ion collisions. PMID- 9970136 TI - Detection of source granularity through multiparticle Bose correlations. PMID- 9970138 TI - Use of the Nambu-Jona-Lasino model in the calculation of the density dependence of four-quark condensates. PMID- 9970137 TI - Forward angle pi +/-p elastic scattering differential cross sections at T pi =87 to 139 MeV. PMID- 9970139 TI - Microscopic model of the timelike electromagnetic form factor of the nucleon. PMID- 9970140 TI - Two-loop calculations with vertex corrections in the Walecka model. PMID- 9970141 TI - Nonperturbative aspects of the quark-photon vertex. PMID- 9970142 TI - Microscopic, model-space approach to parity nonconservation in compound nuclei. PMID- 9970143 TI - Low-multipolarity magnetic transitions in 40Ca excited by 180 degrees electron scattering. PMID- 9970144 TI - Measured static hyperfine magnetic field for Pt in Gd. PMID- 9970145 TI - Absolute level widths in 27Al below 4 MeV. PMID- 9970146 TI - Prompt and isomeric fission of Pu isotopes following heavy-ion induced transfer reactions. PMID- 9970147 TI - Collective motion of reverse-reaction system in the intermediate-energy domain via the quantum-molecular-dynamics approach. PMID- 9970148 TI - Total cross sections for neutron scattering. PMID- 9970149 TI - Relativistic momentum-space optical model and meson-deuteron scattering. PMID- 9970150 TI - Erratum: Theoretical interpretation of the NE18 experiment on nuclear transparency in A(e,e'p) scattering PMID- 9970151 TI - beta -delayed gamma -ray emission in 37Ca decay. PMID- 9970152 TI - Near-threshold production of omega mesons in the pd-->3He omega reaction. PMID- 9970153 TI - Superdeformation in 193Pb and the effects of the N=7 intruder orbital. PMID- 9970154 TI - Photofission of 182W following reabsorption of photopions. PMID- 9970155 TI - Statistical investigation of factors affecting rotational motion in even-even nuclei. PMID- 9970156 TI - C4 symmetry and bifurcation in superdeformed bands. PMID- 9970157 TI - Inversion potential analysis of the nuclear dynamics in the triton. PMID- 9970158 TI - Effects of the Tucson-Melbourne three-nucleon force on proton spectra from kinematically incomplete neutron-deuteron breakup experiments. PMID- 9970160 TI - Investigation of the neutron form factors by inclusive quasielastic scattering of polarized electrons off polarized 3He: A theoretical overview. PMID- 9970159 TI - Realistic phase shift and mixing parameters for elastic neutron-deuteron scattering: Comparison of momentum space and configuration space methods. PMID- 9970161 TI - Multiparticle scattering theory and inclusive cross sections in nuclear collisions. PMID- 9970162 TI - Deuteron polarizability shifts and the deuteron matter radius. PMID- 9970163 TI - High-spin states in the odd-odd nucleus 92Tc. PMID- 9970164 TI - Gamow-Teller strength in 60,62,64Ni(n,p) reactions at 198 MeV. PMID- 9970165 TI - States at Ex=6-13 MeV in 23Na from 19F(6Li,d) at E(6Li)=16 MeV. PMID- 9970166 TI - Light particle emission induced by stopped antiprotons in nuclei: Energy dissipation and neutron-to-proton ratio. PMID- 9970167 TI - pi g9/2 PMID- 9970168 TI - Level structure of the shell-model nucleus 217At. PMID- 9970169 TI - Level structure and reflection asymmetry in 227Th. PMID- 9970170 TI - Level scheme of 101Zr and structure of the N=61 Sr, Zr, and Mo isotones. PMID- 9970171 TI - Observation of dipole transitions to a 2(+) PMID- 9970173 TI - Isospin dependence of the oscillator spacing. PMID- 9970172 TI - Alignments, shape changes, and band terminations in 157Tm. PMID- 9970174 TI - Self-weakening of the tensor interaction in a nucleus. PMID- 9970175 TI - Existence of intrinsic reflection asymmetry at low spin in odd and odd-odd mass nuclei in the Pm/Eu region. PMID- 9970176 TI - Thermodynamical fluctuations of meson fields for a quantum hadrodynamics model. PMID- 9970177 TI - Positive parity states in 11Be. PMID- 9970178 TI - Correlations of intermediate mass fragments from Fe+Ta, Au, and Th collisions. PMID- 9970179 TI - Measurements of proton total reaction cross sections for 58Ni and 60Ni including nonrelativistic and relativistic data analyses. PMID- 9970180 TI - Proton and deuteron production in neutron-induced reactions on carbon at En=42.5, 62.7, and 72.8 MeV. PMID- 9970182 TI - 26Mg(6Li PMID- 9970181 TI - Proton scattering from an excited nucleus (18Fm,J pi =5(+),Ex=1.1 MeV) using a gamma -ray-tagged secondary isomeric nuclear beam. PMID- 9970183 TI - Autocorrelations and intermediate-mass-fragment multiplicities in central heavy ion collisions. PMID- 9970184 TI - Fusion cross sections in systems leading to 170Hf at near-barrier energies. PMID- 9970185 TI - Study of the (1/2)g.s.--->(1/2)1+ transition in the 13C(p,n)13N reaction at intermediate energies. PMID- 9970186 TI - Projectilelike fragment momentum distributions from 86Kr+Al at 70 MeV/nucleon. PMID- 9970188 TI - Multifractal structure of medium energy particles in p-AgBr interactions at 800 GeV. PMID- 9970187 TI - Coupled-channels analysis of the elastic scattering of polarized 6Li by 58Ni using cluster-folding potentials. PMID- 9970189 TI - Dynamical model for correlated two-pion exchange in the pion-nucleon interaction. PMID- 9970191 TI - Medium and finite nuclear size effects in relativistic two-body currents. PMID- 9970190 TI - Unified description for the nuclear equation of state and fragmentation in heavy ion collisions. PMID- 9970193 TI - Symmetrical sum-rule analysis of spectroscopic factors for one-nucleon transfer. PMID- 9970192 TI - Comparison between nonlocal effects and coupled channels in a simple nuclear fusion model. PMID- 9970194 TI - Application of multiple scattering theory to lower-energy elastic nucleon-nucleus scattering. PMID- 9970195 TI - Fragment flow and the nuclear equation of state. PMID- 9970196 TI - Charm production in hadronic and heavy-ion collisions at ultrarelativistic energies to O( alpha s3). PMID- 9970197 TI - Strangeness as probe of quark-gluon plasma: Unconventional point of view. PMID- 9970198 TI - Impact parameter determination for heavy-ion collisions by use of a neural network. PMID- 9970199 TI - Thermal photon production in high-energy nuclear collisions. PMID- 9970200 TI - Freeze-out conditions and pion spectrum in heavy-ion collisions. PMID- 9970201 TI - Collective modes in a strangelet. PMID- 9970202 TI - Spin-orbit force in a quark model based nucleon-nucleon potential. PMID- 9970203 TI - rho, omega, and phi meson-nucleon scattering lengths from QCD sum rules. PMID- 9970204 TI - Parity mixing of the 0(+)-0(-) I=1 doublet in 14N. PMID- 9970206 TI - Positivity restrictions in polarized coincidence electronuclear scattering. PMID- 9970205 TI - Induced parity nonconserving interaction and enhancement of two-nucleon parity nonconserving forces. PMID- 9970207 TI - Stellar neutron capture cross sections of Nd, Pm, and Sm isotopes. PMID- 9970208 TI - Measurement of the 3H( pi +,3He) pi 0 differential cross section at T pi =142 MeV. PMID- 9970209 TI - Association of the 12C+12C breakup states in 24Mg with the quasimolecular resonances. PMID- 9970210 TI - Allowed-unhindered beta decay of 180Yb and the nuclear structure of 180Lu. PMID- 9970212 TI - Higher-order corrections to Coulomb fission. PMID- 9970211 TI - Measurement of the spin-flip probability for the 12C(d PMID- 9970213 TI - Comparison of different Skyrme forces: Fusion barriers and fusion cross sections. PMID- 9970214 TI - Quantal particle flux and nuclear halo effects. PMID- 9970215 TI - Factorization contributions and the breaking of the Delta I=1/2 rule in weak Lambda N rho and Sigma N rho couplings. PMID- 9970216 TI - Limited symmetry found by comparing calculated magnetic dipole spin and orbital strengths in 4He. PMID- 9970217 TI - Apparent Coulomb reacceleration of neutrons in electrodissociation of the deuteron. PMID- 9970218 TI - Isospin recoupling and Bose-Einstein pion correlations in N-barN annihilations. PMID- 9970219 TI - alpha decay of a new isotope, 204Ra. PMID- 9970220 TI - Superdeformation in the bismuth nuclei. PMID- 9970221 TI - Double-octupole excitations in the N=84 nuclei 144Nd and 146Sm. PMID- 9970222 TI - Superdeformed band in 154Dy. PMID- 9970223 TI - Measurement of the reaction 12C( nu micro, micro-)X near threshold. PMID- 9970224 TI - Limits of proton stability near 100Sn. PMID- 9970225 TI - Constraints on coupling constants through charged Sigma photoproduction. PMID- 9970226 TI - Linking of direct and compound chains in multistep nuclear reactions. PMID- 9970227 TI - Low-energy theorem for a composite particle in mean scalar and vector fields. PMID- 9970228 TI - Single-particle nondegeneracy and SU(3) fermion dynamical symmetry. PMID- 9970229 TI - Nature of the identical bands in atomic nuclei. PMID- 9970230 TI - 3H(p, gamma )4He cross section. PMID- 9970231 TI - Orthogonality nodes and the three-body bound state collapse. PMID- 9970233 TI - Extension of fractional parentage expansion to the nonrelativistic and relativistic SUf(3) dibaryon calculations. PMID- 9970232 TI - Electron induced pd and ppn breakup of 3He with full inclusion of final-state interactions. PMID- 9970234 TI - Delta excitation and exchange corrections for NN bremsstrahlung. PMID- 9970235 TI - Excitation of 77Sem, 79Brm, and 191Irm by 137Cs gamma rays. PMID- 9970237 TI - Decay patterns of dysprosium nuclei produced in 32S+118,124Sn fusion reactions. PMID- 9970236 TI - 8Be and alpha decay of 16O. PMID- 9970238 TI - Shape coexistence in the transitional 133Ba nucleus. PMID- 9970239 TI - Experimental and theoretical study of the nuclear structure of 223Fr. PMID- 9970240 TI - Ground-state bands and excitation modes in 183Hg. PMID- 9970241 TI - Isoscalar spin strength in 12C measured in 400 MeV deuteron inelastic scattering. PMID- 9970242 TI - alpha and beta decays of 169-173Os and the nuclear structure of the daughter isotopes. PMID- 9970243 TI - High-K structures in 136Sm. PMID- 9970245 TI - 100Sn-daughter alpha -nuclei cluster decays of some neutron-deficient Xe to Gd parents: Sn radioactivity. PMID- 9970244 TI - Effective nucleon mass, incompressibility, and third derivative of nuclear binding energy in the nonlinear relativistic mean field theory. PMID- 9970247 TI - Small-amplitude limit of the nuclear Born-Oppenheimer method. PMID- 9970246 TI - Canonical and grand-canonical partition functions and level densities. PMID- 9970248 TI - Description of hypernuclei in the scalar derivative coupling model. PMID- 9970250 TI - Spectral function for finite nuclei in the local-density approximation. PMID- 9970249 TI - Symmetric and asymmetric nuclear matter in the relativistic approach. PMID- 9970252 TI - Decoupling and anomalous bandcrossings in odd-proton nuclei. PMID- 9970251 TI - Resurrection of the L-S coupling scheme in superdeformation. PMID- 9970253 TI - Quadrupole-collective states in a large single-j shell. PMID- 9970254 TI - Radial pattern of nuclear decay processes. PMID- 9970255 TI - Fermi hypernetted-chain evaluation of a generalized momentum distribution for model nuclear matter. PMID- 9970256 TI - Configuration of 18{f O}(7.12 MeV, 4(+)). PMID- 9970257 TI - Unified theory of fermion pair to boson mappings in full and truncated spaces. PMID- 9970258 TI - Ingoing-wave boundary condition versus optical model transmission coefficients: A systematic comparison with particle emission data. PMID- 9970259 TI - Inelastic pion scattering from 3H and 3He. PMID- 9970260 TI - Feshbach-Kerman-Koonin model analysis of preequilibrium (p,p') and (p,n) reactions at 12 to 26 MeV. PMID- 9970261 TI - Entrance-channel dependence of the fission dynamics in 19F+209Bi vs 64Ni+165Ho. PMID- 9970262 TI - Inelastic electron scattering from 18O at backward angles. PMID- 9970263 TI - Quasifree (d PMID- 9970264 TI - Excitation functions of the 20Ne+20Ne system. PMID- 9970265 TI - ( gamma,2N) reaction in 12C. PMID- 9970266 TI - Spin alignment for 12C on 12C collisions exciting the 9.64-MeV 3(-) state. PMID- 9970267 TI - 12C( gamma,p)11B cross section from 80 to 157 MeV. PMID- 9970269 TI - Core-polarization effects in pion elastic scattering from polarized spin-1/2 nuclei. PMID- 9970268 TI - Total cross section measurements of 16O+232Th incomplete fusion followed by fission at 140 MeV. PMID- 9970271 TI - Half-lives of cluster radioactivity within a model including superfluid phenomena and resonance effects. PMID- 9970270 TI - Causality with noncausal optical potentials. PMID- 9970272 TI - Isolating physical effects in the exclusive (N,N' pi ) reaction. PMID- 9970273 TI - Nuclear medium effects in the relativistic treatment of quasifree electron scattering. PMID- 9970274 TI - Role of nuclear dynamics in deducing the fusion-fission time scales from prescission neutron multiplicities. PMID- 9970275 TI - Role of final state interactions in quasielastic 56Fe(e,e') reactions at large ||q PMID- 9970276 TI - Folding analysis of the elastic 6Li+12C scattering: Knock-on exchange effects, energy dependence, and dynamical polarization potential. PMID- 9970277 TI - Charge-changing interactions of 197Au at 10 GeV/nucleon in collisions with targets from H to Pb. PMID- 9970278 TI - Thermal tunneling of qq-bar pairs in A-A collisions. PMID- 9970279 TI - Stopped Delta -matter source in heavy-ion collisions at 10 GeV/nucleon? PMID- 9970280 TI - Bose-stimulated pion production in relativistic nuclear collisions. PMID- 9970281 TI - Consequences of a covariant description of heavy-ion reactions at intermediate energies. PMID- 9970282 TI - Correction factors for reactions involving qq-bar annihilation or production. PMID- 9970283 TI - Boundary and Coulomb effects on boson systems in high-energy heavy-ion collisions. PMID- 9970284 TI - Low-energy differential cross sections of pion-proton ( pi +/-p) scattering. I. The isospin-even forward scattering amplitude at T pi =32.2 and 44.6 MeV. PMID- 9970286 TI - Pion and thermal photon spectra as a possible signal for a phase transition. PMID- 9970285 TI - Low-energy differential cross sections of pion-proton ( pi +/-p) scattering. II. Phase shifts at T pi =32.7, 45.1, and 68.6 MeV. PMID- 9970287 TI - Deep-inelastic scattering from the pion and the choice of phenomenological wave functions. PMID- 9970288 TI - Open charm as a probe of preequilibrium dynamics in nuclear collisions. PMID- 9970289 TI - Relativistic nuclear matter with alternative derivative coupling models. PMID- 9970290 TI - Conversion widths of Xi hypernuclear states to double- Lambda states. PMID- 9970291 TI - Pion-nucleon scattering and the pi NN coupling constant in the chiral color dielectric model. PMID- 9970292 TI - Time scale of quasifission from giant dipole resonance gamma -ray yield. PMID- 9970293 TI - Level structure of 114Te. PMID- 9970294 TI - Revised interpretations for K pi =1(+) bands in 166Ho. PMID- 9970295 TI - Evidence for 16O+12C cluster structure in 28Si. PMID- 9970296 TI - Lambda -nucleon interaction in nuclei probed by the quasifree 12C( pi +,K+) reaction. PMID- 9970297 TI - Probing toroidal density distributions with two-proton correlation functions? PMID- 9970298 TI - Symmetry constraints on the classical skyrmion. PMID- 9970299 TI - Consequences of nuclear shadowing for heavy quarkonium production in hadron nucleus interactions. PMID- 9970300 TI - Hexadecapole shape change in ytterbium isotopes. PMID- 9970302 TI - Quark self-energy beyond the mean field at finite temperature. PMID- 9970301 TI - Double-beta decay of 100Mo: The deformed limit. PMID- 9970303 TI - QCD sum rules for Delta isobar in nuclear matter. PMID- 9970304 TI - Threshold parameters of the KK-bar and pi pi scalar-isoscalar interactions. PMID- 9970305 TI - Application of an iterative-perturbative inversion potential model to capture and bremsstrahlung reactions. PMID- 9970306 TI - Relative spins and excitation energies of superdeformed bands in 190Hg: Further evidence for octupole vibration. PMID- 9970307 TI - Can weakly absorbing surface transparent nucleus-nucleus interaction ensure orbiting? PMID- 9970308 TI - Quasiparticle excitations in superdeformed 192Hg. PMID- 9970309 TI - Pion-induced single charge exchange in deuterium. PMID- 9970310 TI - Nuclear transparency in quasifree electron scattering. PMID- 9970311 TI - Nonperturbative and self-consistent determination of baryonic vertex form factors. PMID- 9970312 TI - pi N--> eta N and eta N--> eta N partial-wave T matrices in a coupled, three channel model. PMID- 9970313 TI - Hypervirial approach to calculating expectation values of the many-body Hamiltonian. PMID- 9970314 TI - Proton-proton bremsstrahlung below and above pion threshold: Influence of the Delta isobar. PMID- 9970315 TI - Variational calculations of the Lambda -separation energy of the Lambda 17O hypernucleus. PMID- 9970316 TI - Benchmark solutions for n-d breakup amplitudes. PMID- 9970317 TI - Combined description of N-barN scattering and annihilation with a hadronic model. PMID- 9970318 TI - beta -delayed neutron decay of 14Be. PMID- 9970319 TI - g factor of the 3/2(+) 121.8-keV level in 99Zr. PMID- 9970320 TI - Population of hyperdeformed structures in 152Dy from proton-gamma coincidence experiments. PMID- 9970321 TI - High-spin spectroscopy of 109Te. PMID- 9970323 TI - Electron scattering from 10B. PMID- 9970322 TI - Identification of the unfavored N=7 superdeformed band in 191Hg. PMID- 9970324 TI - Intruder bands in (Z=53) 113I: Band termination interpretation. PMID- 9970325 TI - Lifetimes in the decay of 40Ca and 47V studied by crystal blocking. PMID- 9970326 TI - Possible signatures of shell structure near the drip lines. PMID- 9970327 TI - High-energy scissors mode. PMID- 9970328 TI - Surface response in the Fermi-liquid drop and nuclear transport properties. PMID- 9970329 TI - Auxiliary potential in no-core shell-model calculations. PMID- 9970330 TI - Short range correlations in the weak decay of Lambda hypernuclei. PMID- 9970331 TI - Neutron-proton halo structure of the 3.563-MeV 0(+) state in 6Li. PMID- 9970332 TI - Transverse electric form factors for electron scattering and violation of current conservation in nuclear models. PMID- 9970333 TI - Cranking Bohr-Mottelson Hamiltonian applied to normal bands of odd-A nuclei. PMID- 9970334 TI - Low-lying collective states in 124-132Ba in the framework of the general collective model. PMID- 9970335 TI - First observation of spontaneous fission and search for cluster decay of 232Th. PMID- 9970336 TI - Elastic scattering of pions from 3H and 3He into the backward hemisphere. PMID- 9970337 TI - pi --12C elastic scattering above the Delta resonance. PMID- 9970338 TI - 16O( gamma,n) reaction at intermediate energy. PMID- 9970339 TI - Mass and charge distributions in Fe-induced reactions. PMID- 9970340 TI - Polarization observables in pi d PMID- 9970341 TI - Decay of 160Er* in 16O+144Nd and 64Ni+96Zr fusion reactions. PMID- 9970342 TI - Coupling effects studied in the 13C(p,pn)12C and 13C(p,d)12C reactions at Ep=35 MeV. PMID- 9970343 TI - Rapid increase in prescission giant-dipole-resonance gamma -ray emission with bombarding energy. PMID- 9970344 TI - Breakup studies with 23Na. PMID- 9970345 TI - 12C( gamma,p0+1)11B cross section from 44 to 98 MeV. PMID- 9970346 TI - Cluster radioactivities from an island of cluster emitters. PMID- 9970347 TI - Neutron-halo nuclei in cold synthesis and cluster decay of heavy nuclei: Z=104 nucleus as an example. PMID- 9970348 TI - Molecular-dynamics approach: From chaotic to statistical properties of compound nuclei. PMID- 9970349 TI - Compound nucleus formation in reactions between massive nuclei: Fusion barrier. PMID- 9970351 TI - Xi --hypernuclear states in heavy nuclei. PMID- 9970350 TI - Medium effects on spin observables of proton knockout reactions. PMID- 9970352 TI - Two-body currents in inclusive electron scattering. PMID- 9970353 TI - Spinodal instabilities in expanding Fermi liquids. PMID- 9970354 TI - Analytical treatment of heavy-ion elastic scattering at intermediate energies. PMID- 9970355 TI - Interplay of collective flow phenomena and velocity correlations of intermediate mass fragments in collisions of Au+Au at E=(100-400)A MeV. PMID- 9970356 TI - Method for calculating elastic scattering between two composite many-body systems at high energies. PMID- 9970357 TI - Study of baryon resonances through gamma p--> eta p differential cross sections. PMID- 9970358 TI - Color transparency assumptions. PMID- 9970359 TI - Quark exchange model for charmonium dissociation in hot hadronic matter. PMID- 9970360 TI - Relativistic nuclear structure effects in quasielastic neutrino scattering. PMID- 9970361 TI - Center of mass of a few-body quantum system in an effective central field. PMID- 9970362 TI - Variations of hadron masses and matter properties in dense nuclear matter. PMID- 9970363 TI - No evidence for a 17-keV neutrino in the electron-capture decay of 55Fe. PMID- 9970364 TI - Experimental search for a 17-keV neutrino in the internal bremsstrahlung spectrum of 71Ge. PMID- 9970366 TI - The 12C( alpha, gamma )16O reaction: Effects of nuclear excitation on the breakup of a 16O beam. PMID- 9970365 TI - Radiative decays of the 16.6 and 16.9 MeV states in 8Be and tests of the conservation of the vector current in the A=8 multiplet. PMID- 9970367 TI - Isobaric ratios of fragments emitted in incomplete fusion reactions. PMID- 9970368 TI - Evidence for hexadecapole collectivity in closed-shell nuclei. PMID- 9970369 TI - Measurement of the E2 decay branching ratio of the first excited 0(+) state in 166Er. PMID- 9970370 TI - Observation of a possible pi h11/2 band in 117Cs. PMID- 9970372 TI - High-spin states in 94Tc and the shell-model interpretation. PMID- 9970371 TI - gamma decays of proton unbound levels in 37K. PMID- 9970374 TI - Binding energies of proton-rich nuclei in the vicinity of 100Sn. PMID- 9970373 TI - Asymmetric fission barriers and total kinetic energies for 194Hg, 149Tb, 110 112In, 94Mo, and 75Br. PMID- 9970375 TI - Simulation of the exclusion principle in the neutron-16O interaction through a repulsive term and application to a three-body calculation of the 16O(d,p)17O reaction. PMID- 9970377 TI - Influence of pairing on the (p,t) transition strength between high-spin K isomers of Hf isotopes. PMID- 9970376 TI - Polarization in the pp-->n Delta ++ reaction above 1 GeV. PMID- 9970378 TI - Inelastic K+-nucleus scattering. PMID- 9970379 TI - Simple formula for conditional fission barriers of rotating nuclei. PMID- 9970381 TI - Photon absorption on a proton-proton pair in 3He. PMID- 9970380 TI - What can be learned with an iodine solar-neutrino detector? PMID- 9970382 TI - Erratum: E2 contribution to the 8B-->p+7Be Coulomb dissociation cross section PMID- 9970383 TI - Erratum: Rapidity distribution of photons emitted from a hadronizing quark-gluon plasma PMID- 9970384 TI - eta meson photoproduction on hydrogen near threshold. PMID- 9970385 TI - Neutron blocking and delayed proton pair alignment in superdeformed 195Pb. PMID- 9970387 TI - Analytic interpretation of universal anharmonic vibrator behavior in the interacting boson approximation model. PMID- 9970386 TI - Evidence for the possible synthesis of element 110 produced by the 59Co+209Bi reaction. PMID- 9970388 TI - Effect of sigma - omega - gamma mixing on the dimesonic function in nuclear matter. PMID- 9970389 TI - Two-pion correlation behavior in a small relative momentum region. PMID- 9970390 TI - Triton calculations with pi and rho exchange three-nucleon forces. PMID- 9970391 TI - Properties of the bound Lambda ( Sigma )NN system and hyperon-nucleon interactions. PMID- 9970392 TI - Effects of T- and P-odd weak nucleon interaction in nuclei: Renormalizations due to residual strong interaction, matrix elements between compound states and their correlations with P-violating matrix elements. PMID- 9970393 TI - Universality of Delta I=1 meson mixing and charge symmetry breaking. PMID- 9970394 TI - Rotational bands in 76Rb. PMID- 9970395 TI - Energy variation of nuclear level density in 104Pd and 114Sn in the excitation energy region of 7 to 24 MeV. PMID- 9970396 TI - Search for two-phonon gamma vibrational states in 164Dy. PMID- 9970397 TI - High-spin structure of 82Y. PMID- 9970398 TI - Description of the scissors mode within the Moszkowski model. PMID- 9970399 TI - Ground-state magnetization of 209Bi in a dynamic-correlation model. PMID- 9970400 TI - Quantum rotational band formulas from a two-parameter potential and the microscopic explanation from the fermion dynamical symmetry model. PMID- 9970402 TI - Laboratory cranking wave functions and ground-state moments of inertia of heavy deformed nuclei. PMID- 9970401 TI - Description of the 2 nu beta beta transition rate within the Moszkowski model. PMID- 9970403 TI - Energies and widths of low-lying levels in 11Be and 11N. PMID- 9970404 TI - Propagation of a K-body force into A-body space. PMID- 9970405 TI - Momentum and energy distributions of nucleons in finite nuclei due to short-range correlations. PMID- 9970406 TI - Three-body halos. III. Effects of finite core spin. PMID- 9970407 TI - Extended random-phase approximation in a boson formalism with Pauli principle. PMID- 9970408 TI - Delta K forbiddenness in neutron capture resonances in 177Lu. PMID- 9970409 TI - Nuclear structure effects of the nuclei 152,154,156Dy at high excitation energy and large angular momentum. PMID- 9970410 TI - Numerical simulation of the electromagnetic decay of the nuclei 152,154,156Dy with self-consistent collective strength functions. PMID- 9970411 TI - Emission angle dependence of fission fragment spin: Effects of single particle spin and tilting mode. PMID- 9970412 TI - Fission-fragment angular distributions and excitation functions in fission following complete fusion and targetlike-fragment fission reactions of 19F+232Th at near- and sub-barrier energies. PMID- 9970413 TI - Momentum distributions of 9Li fragments from the breakup of 11Li and the neutron halo. PMID- 9970414 TI - Prescission neutron emission in 235U(nth,f) through fragment-neutron angular correlation studies. PMID- 9970415 TI - Azimuthal distributions and collective motion in intermediate energy heavy-ion collisions. PMID- 9970416 TI - Dynamical effects in fusion reactions forming 110Sn. PMID- 9970417 TI - Transitions in nuclear disassembly as viewed by fragment charge correlations. PMID- 9970418 TI - Zero-degree proton inelastic scattering to the 1(+), T=0 and T=1 states in 12C. PMID- 9970419 TI - Pion double charge exchange on the even selenium isotopes. PMID- 9970420 TI - Final-state interactions in the 12C(16O,12C12C) alpha and 16O(16O,12C16O) alpha reactions. PMID- 9970421 TI - Light charged particles from low-energy 58Ni+112Sn fusion-evaporation reactions. PMID- 9970423 TI - Analysis of multifragmentation in a Boltzmann-Langevin approach. PMID- 9970422 TI - Effects of finite excitation energy of environment on fast quantum tunneling. PMID- 9970424 TI - Analysis of compound and quasicompound resonances in a multichannel, finite-rank model. PMID- 9970425 TI - Instant two-body equation in Breit frame. PMID- 9970426 TI - Memory and correlation effects in nuclear collisions. PMID- 9970427 TI - alpha -d capture with formation of 6Li and the isoscalar E1 multipole. PMID- 9970428 TI - Relativistic versus nonrelativistic optical potentials in A(e,e'p)B reactions. PMID- 9970430 TI - Fine structure in the cluster decays of the translead nuclei. PMID- 9970429 TI - Correlation functions and the disappearance of rotational collective motion in nucleus-nucleus collisions below 100 MeV/nucleon. PMID- 9970431 TI - Spin dependence of the scattering of protons from halo nuclei. PMID- 9970432 TI - A potential deduced from low energy 16O( alpha, alpha ) elastic scattering. PMID- 9970433 TI - Fragmentation cross sections of 16O, 24Mg, and 32S projectiles at 3.65 GeV/nucleon. PMID- 9970435 TI - Disappearance of flow. PMID- 9970434 TI - Charged-particle pseudorapidity distributions in Au+Al, Cu, Au, and U collisions at 10.8A GeV/c. PMID- 9970436 TI - Open charm production in an equilibrating parton plasma. PMID- 9970438 TI - Azimuthal correlations of pions in relativistic heavy-ion collisions at 1 GeV/nucleon. PMID- 9970437 TI - Geometrical description for the negative correlation between forward and transverse energies in ultrarelativistic heavy-ion collisions. PMID- 9970439 TI - Role of dynamical correlations in fragment formation in heavy-ion collisions. PMID- 9970440 TI - Neutron-electron scattering length and electric polarizability of the neutron derived from cross sections of bismuth and of lead and its isotopes. PMID- 9970441 TI - Nuclear many-body theory for the study of QCD sum rules in matter. PMID- 9970442 TI - Static properties of the nucleon in the Faddeev approach based on the Nambu-Jona Lasinio model. PMID- 9970443 TI - Inelastic diffractive production and string fusion in hadron-nucleus collisions. PMID- 9970444 TI - Off-shell rho - omega mixing through quark loops with a nonperturbative meson vertex and quark mass functions. PMID- 9970446 TI - Short range correlation effect on the pion propagator in nuclear matter. PMID- 9970445 TI - Quark delocalization, color screening, and dibaryons. PMID- 9970448 TI - Correlation effects in nuclear transparency. PMID- 9970447 TI - Composite vertices that lead to soft form factors. PMID- 9970449 TI - Quark model description of the N-N system: Momentum distributions, structure functions, and the EMC effect. PMID- 9970450 TI - Quantum field kinetics. PMID- 9970451 TI - Stellar (n, gamma ) cross section of the unstable isotope 155Eu. PMID- 9970452 TI - Possibility to determine the astrophysical S factor for the 7Be(p, gamma )8B radiative capture from analysis of the 7Be(3He,d)8B reaction. PMID- 9970453 TI - Out-of-plane quasielastic scattering from deuterium using polarized electrons. PMID- 9970454 TI - Static quadrupole moment of high-spin isomers in the doubly-odd 214Fr nucleus. PMID- 9970455 TI - 36Ca beta decay and the isobaric multiplet mass equation. PMID- 9970456 TI - Space-time ambiguity of two- and three-fragment reduced velocity correlation functions. PMID- 9970457 TI - Excitation energies in statistical emission of light charged particles in heavy ion reactions. PMID- 9970458 TI - Absolute cross sections for ( gamma,n) transitions in lead, bismuth, and terbium. PMID- 9970459 TI - Search for a 7- alpha chain state. PMID- 9970460 TI - Ec.m.=32.5 MeV resonance in 12C+12C. PMID- 9970461 TI - Modified two-sources quantum statistical model and multiplicity fluctuation in the finite rapidity region. PMID- 9970462 TI - Magnetic octupole strength in rare-earth nuclei: A sum-rule approach. PMID- 9970463 TI - Effect of relativistic kinematics on the quark-quark interaction obtained from the proton form factor. PMID- 9970464 TI - Complete J=0 calculation in the sp(6) PMID- 9970465 TI - Comment on "Modified Glauber model II description for heavy-ion scattering" PMID- 9970466 TI - Comment on "New interpretation of the lowest K=0 collective excitations of deformed nuclei as a phonon excitation of the gamma band" PMID- 9970467 TI - Nature of the lowest excited K pi =0(+) states of even-even deformed nuclei. PMID- 9970468 TI - Reply to "Comments on 'New interpretation of the lowest K=0 collective excitation of deformed nuclei as a phonon excitation of the gamma band' " PMID- 9970469 TI - Comment on "High spin states of 84Sr" PMID- 9970470 TI - Yrast bands in 117I and 116-118Xe: Anomalous quasiparticle alignment frequencies and band termination. PMID- 9970472 TI - Coexistence effects in 187Au: Evidence for nearly identical diabatic intruder structures. PMID- 9970471 TI - 6Li( pi +, pp)4Heg.s. reaction at 100 and 165 MeV incident pion energies. PMID- 9970473 TI - Spin-flip strength in the continuum and effective tensor interactions via polarization transfer DNN(0 degrees) for (p PMID- 9970474 TI - First observation of a rotational band in odd 50Sn nuclei: 111Sn. PMID- 9970475 TI - Generator-coordinate method study of hexadecapole correlations in superdeformed 194Hg. PMID- 9970476 TI - Fast gamma -ray transitions between excited states as evidence of order in deformed nuclei. PMID- 9970477 TI - Thermal photons from S+Au collisions at 200A GeV: A hadron gas picture. PMID- 9970479 TI - 500-MeV pion single-charge exchange on deuterium. PMID- 9970478 TI - Okubo-Zweig-Iizuka rule violation in the reaction p-barp--> phi pi 0. PMID- 9970481 TI - Pion photoproduction of the deuteron: The reaction gamma d--> pi 0d. PMID- 9970480 TI - Microscopic description of the nucleon- Delta interaction in the quark cluster model. PMID- 9970482 TI - Multipole strength in 12C from the (e,e' alpha ) reaction for momentum transfers up to 0.61 fm-1. PMID- 9970483 TI - High-spin bands in 80Kr. PMID- 9970484 TI - beta decay of 228Ra and possible level structures in 228Ac. PMID- 9970485 TI - Proton and neutron excitations in superdeformed 150Tb. PMID- 9970486 TI - Strong population of a superdeformed band in 142Eu. PMID- 9970487 TI - Band structures in 108Ag. PMID- 9970489 TI - 128,130,132,134La in the axially symmetric rotor model. PMID- 9970488 TI - alpha decay of the new isotopes 210Th and 211Th. PMID- 9970490 TI - Structural properties of hot deformed 122Xe at high spins. PMID- 9970492 TI - Relativistic density-dependent Hartree-Fock approach for finite nuclei. PMID- 9970491 TI - Effective nucleon mass, incompressibility, and third-order derivative of the nuclear saturation curve in the relativistic mean field theory with vector meson self-interaction. PMID- 9970493 TI - Surface properties of Cs isotopes. PMID- 9970495 TI - Towards a model independent analysis of single particle spectra: Application to hypernuclei. PMID- 9970494 TI - Density functional approach to quantum hadrodynamics: Local exchange potential for nuclear structure calculations. PMID- 9970497 TI - Thermal effects on isoscalar giant resonance energies in hot nuclei. PMID- 9970496 TI - Microscopic analysis of collective states in neutron-deficient doubly even xenon isotopes. PMID- 9970498 TI - Quasielastic scattering of 8B and 7Be on 12C at 40 MeV/nucleon. PMID- 9970500 TI - Heavy-residue production in Ar-Th collisions at 44, 77, and 95 MeV/nucleon. PMID- 9970499 TI - Negative pion photoproduction from 15N in the region of the Delta resonance. PMID- 9970501 TI - Internal excitation of intermediate mass fragments from collisions of 36Ar+Ag nuclei at 35 MeV/nucleon. PMID- 9970502 TI - Cross sections and analyzing powers for quasielastic scattering at 795 and 495 MeV using the (p PMID- 9970503 TI - Resolution of the anomalous fission fragment anisotropies for the 16O+208Pb reaction. PMID- 9970504 TI - Fluctuation effects in radiative capture to unstable final states: A test via the 89Y(p PMID- 9970505 TI - 223Ra nuclear spectroscopy in 14C cluster radioactivity. PMID- 9970506 TI - Critical evolution of a finite system. PMID- 9970507 TI - Path integral approach to no-Coriolis approximation in heavy-ion collisions. PMID- 9970508 TI - Proton scattering by 206,207,208Pb at 650 MeV: Phenomenological analysis. PMID- 9970510 TI - Proton inelastic scattering to continuum studied with antisymmetrized molecular dynamics. PMID- 9970509 TI - In-medium full-folding optical model for nucleon-nucleus elastic scattering. PMID- 9970512 TI - Emission of fast protons in high-energy hadron-emulsion interactions. PMID- 9970511 TI - Radial flow and multifragmentation within the framework of molecular dynamics approaches. PMID- 9970513 TI - Charge-changing fragmentation of 10.6 GeV/nucleon 197Au nuclei. PMID- 9970515 TI - Centrality dependence of pion and proton spectra in C+C and C+Ta interactions at 4.2 GeV/c per nucleon. PMID- 9970514 TI - Entropy in central Au+Au reactions between 100 and 400A MeV. PMID- 9970517 TI - Cluster production with coalescence and breakup. PMID- 9970516 TI - Monte Carlo model for multiparticle production at ultrarelativistic energies. PMID- 9970519 TI - Initial-state interactions for K--proton radiative capture. PMID- 9970518 TI - Masses of hadrons and nucleon-nucleon interaction at finite temperature and density in a quantum hadrodynamics model. PMID- 9970520 TI - Gluon decay as a mechanism for strangeness production in a quark-gluon plasma. PMID- 9970521 TI - Effects of N-barN polarization on vector meson masses at finite temperature. PMID- 9970522 TI - Excitation energies in 20Na above the proton threshold. PMID- 9970523 TI - Reaction cross sections of intermediate energy alpha particles within a relativistic optical model. PMID- 9970524 TI - Unusual nuclear shapes and neutron specific heat of neutron star crusts. PMID- 9970525 TI - Glueball production from the quark-gluon plasma. PMID- 9970526 TI - 1/Nc rotational corrections to gA in the Nambu-Jona-Lasinio model and charge conjugation. PMID- 9970527 TI - Dilepton production from pion annihilation in a realistic Delta -hole model. PMID- 9970528 TI - Cranking Bohr-Mottelson Hamiltonian applied to superdeformed bands in the A~150 region. PMID- 9970529 TI - Electroproduction of N*(1535). PMID- 9970530 TI - Erratum: Nucleon polarization in three-body models of polarized 6Li PMID- 9970531 TI - Erratum: Open charm as a probe of preequilibrium dynamics in nuclear collisions? PMID- 9970533 TI - Decay out of the highly deformed bands in the odd Nd isotopes: The 137Nd nucleus. PMID- 9970532 TI - Collectivity in "spherical" 143,144Eu nuclei. PMID- 9970534 TI - Optical-model analysis of parity-nonconserving neutron scattering at epithermal energies. PMID- 9970535 TI - Cross section, polarization observables, and phase-shift parameters in p-d and n d elastic scattering. PMID- 9970536 TI - Neutron halos in O isotopes. PMID- 9970538 TI - Nuclear transparencies for nucleons, knocked-out under various semi-inclusive conditions. PMID- 9970537 TI - Microscopic mass formulas. PMID- 9970540 TI - Exact solution of the bound-state Faddeev-Yakubovsky equations for one dimensional systems with a delta -function interaction. PMID- 9970539 TI - Measurement of np-->pp pi - at 443 MeV. PMID- 9970541 TI - NN--> Delta N transition amplitude analysis in the density matrix formalism. PMID- 9970542 TI - Chiral background for the two-pion exchange nuclear potential: A parametrized version. PMID- 9970543 TI - Quark cluster model study of isospin-2 dibaryons. PMID- 9970545 TI - Gauge invariant unitary theory for pion photoproduction. PMID- 9970544 TI - Are there eta -helium bound states? PMID- 9970546 TI - Relativistic nuclear Hamiltonians. PMID- 9970547 TI - Variational Monte Carlo calculations of 3H and 4He with a relativistic Hamiltonian. PMID- 9970548 TI - Spin-induced shape changes in light-medium mass compound nuclei. PMID- 9970549 TI - New high-spin band structures in 184Hg. PMID- 9970550 TI - Direct proton decay from the Gamow-Teller resonance in 208Bi. PMID- 9970551 TI - Doppler-shift attenuation method lifetime measurements in 115Sb and 117Sb. PMID- 9970553 TI - Structure of Li and Be isotopes studied with antisymmetrized molecular dynamics. PMID- 9970552 TI - Onset of collectivity in neutron deficient 196,198Po. PMID- 9970554 TI - Neutron-rich B isotopes studied with antisymmetrized molecular dynamics. PMID- 9970555 TI - Charge densities of the nuclei 86Sr, 89Y, 92Mo, 118Sn, and 152Sm and the proton occupancies of the shells 2s, 2p, 1g, and 1h. PMID- 9970556 TI - Correlations in a many-body calculation of 11Li. PMID- 9970557 TI - Liquid drop surface dynamics for large nuclear deformations. PMID- 9970558 TI - Multiband theory for heavy-ion neutron-pair transfer among deformed Gd nuclei. PMID- 9970560 TI - Halo structure of 14Be in a microscopic 12Be+n+n cluster model. PMID- 9970559 TI - Stochastic aspects of nuclear large amplitude motion. PMID- 9970561 TI - Saturation properties and incompressibility of nuclear matter: A consistent determination from nuclear masses. PMID- 9970562 TI - Shell-model Monte Carlo studies of fp-shell nuclei. PMID- 9970563 TI - Microscopic calculation for alpha and heavier cluster emissions from proton rich Ba and Ce isotopes. PMID- 9970564 TI - Excitation functions of (p, alpha ) reactions on 64Ni, 78Kr, and 86Sr. PMID- 9970566 TI - Elastic scattering and quasielastic transfer for 32S+96,100Mo at Elab=180 MeV. PMID- 9970565 TI - Identification of the new isotope 114Ba and search for its alpha and cluster radioactivity. PMID- 9970567 TI - Photon scattering from 12C and 4He nuclei near the Delta (1232) resonance. PMID- 9970568 TI - Central collisions in the 16O+12C reaction at 32.5 MeV/nucleon. PMID- 9970569 TI - Comparative experimental study of the mirror 13N+12C and 13C+12C elastic scatterings. PMID- 9970570 TI - Impact parameter selected excited state populations for 36Ar+197Au reactions at E/A=35 MeV. PMID- 9970571 TI - Intermediate mass fragments emission in the reaction 47 MeV 7Li+Mg. PMID- 9970572 TI - Spin observables in elastic proton scattering from polarized 3He. PMID- 9970573 TI - Space-time characteristics of fragment emission in the E/A=30 MeV 129Xe+natCu reaction. PMID- 9970574 TI - Algebraic-eikonal approach to medium energy proton scattering from odd-mass nuclei. PMID- 9970575 TI - Imaginary part of the optical potential for finite temperature and for preequilibrium processes. PMID- 9970576 TI - Fully microscopic model of 200 MeV proton-12C elastic and inelastic scattering. PMID- 9970577 TI - Proton-nucleus scattering based on the relativistic Brueckner-Hartree-Fock model. PMID- 9970578 TI - (p,2p) reaction in zero-range and finite-range relativistic distorted-wave impulse approximation. PMID- 9970579 TI - Nuclear binding effects in relativistic Coulomb sum rules. PMID- 9970580 TI - Intermittency in microscopic simulations of multifragmentation. PMID- 9970581 TI - Gamma-ray strength functions at finite temperature. PMID- 9970582 TI - Hadron-nucleon total cross section fluctuations from hadron-nucleus total cross sections. PMID- 9970583 TI - Spin-dependent nuclear structure functions: General approach with application to the deuteron. PMID- 9970584 TI - Neutron-to-proton ratio in intermediate-energy nuclear reactions. PMID- 9970586 TI - Nonlinear Landau damping in quark-gluon plasma. PMID- 9970585 TI - Production of neutron-rich isotopes from the fragmentation of 28Si projectiles at plab=14.6 GeV/c per nucleon. PMID- 9970587 TI - Deuteron formation in expanding nuclear matter from a strong coupling BCS approach. PMID- 9970589 TI - Quark and gluon distributions at the earliest stage of heavy-ion collisions. PMID- 9970588 TI - Relationship between correlation function fit parameters and source distributions. PMID- 9970590 TI - Delta (1232) in nuclei and QCD sum rules. PMID- 9970592 TI - Tests of time-reversal invariance in nuclear and particle physics. PMID- 9970591 TI - Further studies on the evidence for a 17-keV neutrino in a 14C-doped germanium detector. PMID- 9970594 TI - Isospin-breaking corrections to nucleon electroweak form factors in the constituent quark model. PMID- 9970593 TI - Relativistic mean-field approach to anapole moment: Atomic parity-violating hyperfine transitions. PMID- 9970595 TI - Can pions created in high-energy heavy-ion collisions produce a Centauro-type effect? PMID- 9970596 TI - Proton capture reaction rates in the rp process. PMID- 9970597 TI - Screening of nuclear reactions in the Sun and solar neutrinos. PMID- 9970598 TI - Resonance neutron capture in 136Ba. PMID- 9970600 TI - Dirac analysis of deformation parameters in the 12C(p PMID- 9970599 TI - Charge-pickup processes in relativistic heavy-ion reactions. PMID- 9970601 TI - Integral characteristic parameters of the giant M1 resonance. PMID- 9970602 TI - Temperature dependence of the level density parameter. PMID- 9970603 TI - Giant quadrupole excitation in nuclei with neutron skin. PMID- 9970604 TI - Stability of bound states of negative pions and neutrons. PMID- 9970605 TI - 7Be(p, gamma )8B cross section and the properties of 7Be. PMID- 9970607 TI - Regular suppression of P,T-violating nuclear matrix elements. PMID- 9970606 TI - Photoproduction of the eta ' mesons as a new tool to probe baryon resonances. PMID- 9970608 TI - 4H clustering in lithium nuclei. PMID- 9970610 TI - Comment on "Antiproton-proton partial-wave analysis below 925 MeV/c" PMID- 9970609 TI - Reply to 'Comment on "4H clustering in lithium nuclei" ' PMID- 9970611 TI - Reply to "Comment on 'Antiproton-proton partial-wave analysis below 925 MeV/c' " PMID- 9970612 TI - Erratum: Study of 110Cd from the 110Inm beta decay PMID- 9970613 TI - Study of the isospin response of the 4He continuum using the 4He(p,p'X) reaction. PMID- 9970614 TI - Intruder bands extended in 175Re and 177Ir: Deformation changes and interaction at the alignment of i13/2 neutrons. PMID- 9970615 TI - New measurements of 2H( gamma PMID- 9970616 TI - Study of the 18F(p, alpha )15O reaction at astrophysical energies using a 18F beam. PMID- 9970617 TI - Laser oriented 36K for time reversal symmetry measurements. PMID- 9970618 TI - Strong dipole excitations around 1.8 MeV in 238U. PMID- 9970619 TI - Relations between isoscalar charge form factors of two- and three-nucleon systems. PMID- 9970621 TI - Inclusion of fluctuations in Boltzmann-Uehling-Uhlenbeck dynamics: A method of simulation. PMID- 9970620 TI - Suppression of dilepton production in hot hadronic matter. PMID- 9970622 TI - Pion-nucleus scattering and baryon resonances in the nuclear medium. PMID- 9970623 TI - Measuring hadron properties at finite temperature. PMID- 9970624 TI - Analyzing powers of p+d scattering below the deuteron breakup threshold. PMID- 9970625 TI - pi NN coupling constants from NN elastic data between 210 and 800 MeV. PMID- 9970626 TI - Charge symmetry breaking in 500 MeV nucleon-trinucleon scattering. PMID- 9970627 TI - Inclusive electron scattering on 3H and 3He with full inclusion of final state interactions. PMID- 9970628 TI - Nucleon polarization in exclusive deuteron electrodisintegration with polarized electrons and a polarized target. PMID- 9970629 TI - Effects of the three-nucleon forces due to pi and rho meson exchanges in the three-nucleon continuum. PMID- 9970630 TI - Instant form dynamics of one particle exchange models. PMID- 9970631 TI - High-spin structure of 139Eu. PMID- 9970632 TI - E1 and M1 strengths studied from two-step gamma cascades following capture of thermal neutrons in 162Dy. PMID- 9970633 TI - Negative-parity states near the yrast line in 144Nd. PMID- 9970635 TI - Spin-rotor interpretation of identical bands and quantized alignment in superdeformed A PMID- 9970634 TI - Superdeformation in 146Gd. PMID- 9970636 TI - Measurement of low-lying states in 9B. PMID- 9970637 TI - Rotational structures in 177Ta. PMID- 9970638 TI - Evidence of unique-parity band structure in neutron-rich odd-A Ru isotopes. PMID- 9970639 TI - Structure of 108,110,112Ru: Identical bands in 108,110Ru. PMID- 9970640 TI - Conversion electron spectroscopy at the fragment mass analyzer focal plane: Studies of isomeric decays near the proton drip line. PMID- 9970641 TI - Neutron decay from the isobaric analog state in 120Sb populated in 120Sn(3He,t)120Sb at E(3He) = 200 MeV, theta = 0 degrees. PMID- 9970642 TI - Vacuum contributions in a chiral effective Lagrangian for nuclei. PMID- 9970644 TI - Boson-fermion mapping of collective fermion-pair algebras. PMID- 9970643 TI - Deformation of light xenon isotopes. PMID- 9970646 TI - F-spin mixing and M1 properties of the low-lying states in the neutron-proton interacting boson model. PMID- 9970645 TI - Multiparticle-rotor model for rotational band structure of 154Gd. PMID- 9970647 TI - Nuclear incompressibility: An analytical study on the leptodermous expansion. PMID- 9970648 TI - Structure of hot rotating s-d shell nuclei. PMID- 9970649 TI - Regional regularities for the even-even nuclei: Medium to heavy systems. PMID- 9970650 TI - Heavy residues from very mass-asymmetric heavy-ion reactions. PMID- 9970651 TI - Two proton and two neutron photoemission cross sections of 63Cu. PMID- 9970652 TI - Gamow-Teller strength in 23Na(n,p) and a comparison to 23Na( micro-, nu ). PMID- 9970653 TI - Total cross section and resonance spectroscopy for n+122Sn. PMID- 9970654 TI - Photoexcitation of 189Osm and 193Irm. I. Excitation of 189Osm by low-energy x rays. PMID- 9970655 TI - Photoexcitation of 189Osm and 193Irm. II. Excitation by 137Cs and 60Co gamma rays. PMID- 9970656 TI - Measurement of the spin-dependent asymmetry in 3He PMID- 9970658 TI - Correlated pair conversion in heavy-ion collisions at the Coulomb barrier. PMID- 9970657 TI - Coupled channel folding model description of alpha scattering from 9Be. PMID- 9970660 TI - Fission following complete fusion for 16O + 232Th at 140 MeV. PMID- 9970659 TI - Folded potential analysis of the excitation of giant resonances by heavy ions. PMID- 9970661 TI - Intermittency and multifractality of medium-energy particles in proton-nucleus interactions at 800 GeV. PMID- 9970662 TI - Search for H dibaryon-nucleus bound states in relativistic Au+Pt collisions. PMID- 9970664 TI - Correlations and fluctuations in high-energy nuclear collisions. PMID- 9970663 TI - Microcanonical treatment of hadronizing the quark-gluon plasma. PMID- 9970665 TI - Strangeness enhancement in p+A and S+A interactions at energies near 200A GeV. PMID- 9970666 TI - Nucleon to Delta weak excitation amplitudes in the nonrelativistic quark model. PMID- 9970667 TI - Kaon photoproduction off nucleons in the chiral quark model. PMID- 9970669 TI - Variational Tamm-Dancoff treatment of quantum chromodynamics: The heavy mesons in the valence quark approximation. PMID- 9970668 TI - Kaon photoproduction in the color-dielectric model. PMID- 9970670 TI - Indirect study of low-energy resonances in 31P(p, alpha )28Si and 35Cl(p, alpha )32S. PMID- 9970671 TI - High-spin states in doubly odd 114I. PMID- 9970672 TI - gamma -ray deexcitations in 168Tm. PMID- 9970673 TI - Comparison of potential models with the np scattering data below 350 MeV. PMID- 9970675 TI - Comment on "E2 contribution to the 8B-->p+7Be Coulomb dissociation cross section" PMID- 9970674 TI - Phase-shift analysis of neutron-209Bi scattering and its comparison to neutron 208Pb scattering. PMID- 9970676 TI - Reply to "Comment on 'E2 contribution to the 8B-->p+7Be Coulomb dissociation cross section' " PMID- 9970677 TI - Is large weak mixing in heavy nuclei consistent with atomic experiments? PMID- 9970678 TI - Reply to "Is large weak mixing in heavy nuclei consistent with atomic experiments?" PMID- 9970679 TI - The 12C( gamma,K+) reaction in the threshold region. PMID- 9970680 TI - (d,2He) reactions at Ed=125.2 MeV. PMID- 9970681 TI - Evidence for a proton halo in 8B: Enhanced total reaction cross sections at 20 to 60 MeV/nucleon. PMID- 9970682 TI - Superdeformation in 154Er. PMID- 9970683 TI - Isospin mixing in proton-rich N PMID- 9970685 TI - Finite-temperature corrections in the dilated chiral quark model. PMID- 9970684 TI - Nuclear shell structure and chaotic dynamics in hexadecapole deformation. PMID- 9970686 TI - Color fluctuations in hadrons and proton coherent diffractive dissociation on helium. PMID- 9970687 TI - Three-baryon Lambda NN potential. PMID- 9970688 TI - Longitudinal response functions of 3He and 3H by Lorentz kernel transformations. PMID- 9970689 TI - Search for enhanced octupole correlations in 65Ge. PMID- 9970690 TI - Lifetime measurements in 120Xe. PMID- 9970691 TI - Measurement of the magnetic moment of the 10(+) isomer in 132Ba. PMID- 9970692 TI - Are octupole vibrations harmonic? PMID- 9970694 TI - Bands observed in 102Ru using the incomplete fusion reaction. PMID- 9970693 TI - Excitation energy of the pi s1/2 intruder state in 189Bi. PMID- 9970695 TI - Chaotic behavior in the cranking and particles-rotor models. PMID- 9970697 TI - Unified treatment of scattering and cluster structure in alpha +closed shell nuclei: 20Ne and 44Ti. PMID- 9970696 TI - Time-odd components in the mean field of rotating superdeformed nuclei. PMID- 9970698 TI - Pairing correlations between the normal and abnormal parity orbits and the mechanism of the stretching effect. PMID- 9970700 TI - Two-parameter formula for rotational spectra. PMID- 9970699 TI - Unified description of the low lying states of the ground bands of even-even nuclei. PMID- 9970701 TI - Spontaneous-fission half-lives of deformed superheavy nuclei. PMID- 9970702 TI - Shell model study of the high spin states in the N=50 isotones 92Mo, 93Tc, 94Ru, and 95Rh. PMID- 9970703 TI - Unique potentials for the elastic scattering of 350 MeV 7Li from 12C and 28Si. PMID- 9970705 TI - Emission of photons in spontaneous fission of 252Cf. PMID- 9970704 TI - The sphericity of central heavy-ion reactions. PMID- 9970706 TI - Tensor effects in 6Li PMID- 9970707 TI - Population of collective bands in Dy isotopes using heavy ion induced transfer reactions. PMID- 9970708 TI - Excitation functions and isomeric cross section ratio of the 58Ni(n,p)58Com,g reactions from 2 to 15 MeV. PMID- 9970709 TI - Phenomenological transition amplitudes in selected 1p-shell nuclei. PMID- 9970710 TI - Exclusive charged pion photoproduction in selected light nuclei. PMID- 9970712 TI - In-medium effects at low temperatures in the photon bremsstrahlung. PMID- 9970711 TI - Photon polarization in the 4He( gamma,d PMID- 9970714 TI - Comparing the p-wave multipoles for pi 0 photoproduction with low-energy predictions. PMID- 9970713 TI - Anomalous anisotropies of fission fragments for sub-barrier fusion-fission reactions. PMID- 9970715 TI - Propagator modifications in elastic nucleon-nucleus scattering within the spectator expansion. PMID- 9970716 TI - The fragment coalescence model. PMID- 9970717 TI - Effects of Gogny-type interactions on the nuclear flow. PMID- 9970718 TI - Collective reactions to the continuum in neutron scattering by niobium. PMID- 9970720 TI - Formation of superdense hadronic matter in high energy heavy-ion collisions. PMID- 9970719 TI - Tranverse energy and charged particle multiplicity in p-nucleus collisions at 14.6 GeV/c. PMID- 9970722 TI - Ratios of strange antibaryons to baryons in relativistic nucleus-nucleus collisions. PMID- 9970721 TI - Energy constraint effects on pion multiplicity distribution. PMID- 9970723 TI - Phase transitions in warm, asymmetric nuclear matter. PMID- 9970724 TI - Factorial correlator study in 32S-Ag/Br interaction at 200A GeV. PMID- 9970726 TI - Electromagnetic meson form factors in a covariant Salpeter model. PMID- 9970725 TI - Measurement of the electric and magnetic polarizabilities of the proton. PMID- 9970727 TI - Updated analysis of pi N elastic scattering data to 2.1 GeV: The baryon spectrum. PMID- 9970729 TI - K-N S channel I=1,0 phase shifts as a direct measure of chiral condensation. PMID- 9970728 TI - Baryon mappings applied to the three-color delta model. PMID- 9970730 TI - NN-bar annihilation in large NC QCD with rho and omega mesons. PMID- 9970731 TI - Nambu-Jona-Lasinio model compared with chiral perturbation theory: The pion radius in SU(2) revisited. PMID- 9970732 TI - Chiral prediction for the pi N S-wave scattering length a- to order PMID- 9970733 TI - eta N S-wave scattering length in a three-coupled-channel, multiresonance, unitary model. PMID- 9970734 TI - Three-flavor quark matter in the chiral color dielectric model. PMID- 9970735 TI - Neutrino magnetic moment effects in neutrino nucleus reactions. PMID- 9970736 TI - Excitation of the 2.65 MeV state in the 20Ne(p,n)20Na reaction at 135 MeV. PMID- 9970737 TI - Response of mica to weakly interacting massive particles. PMID- 9970738 TI - Pion and neutron production by cosmic-ray muons underground. PMID- 9970739 TI - Two-neutron capture reactions in supernovae neutrino bubbles. PMID- 9970740 TI - Decays of 160-162Hf. PMID- 9970742 TI - Ground-state properties of strontium isotopes. PMID- 9970741 TI - Half-lives of isomeric states in 57Fe and 83Kr. PMID- 9970743 TI - Extraction of the pi NN coupling constant from NN scattering data. PMID- 9970744 TI - Crystalline structure of the mixed confined-deconfined phase in neutron stars. PMID- 9970745 TI - Even-odd staggering of pairing-force strength. PMID- 9970746 TI - Continuum Tamm-Dancoff approximation calculations for the escape widths of the isobaric analog state and Gamow-Teller resonance in 208Bi. PMID- 9970747 TI - 1d5/2-2s1/2 splitting in light nuclei. PMID- 9970748 TI - Particle evaporation following multinucleon transfer processes with radioactive beams. PMID- 9970750 TI - Erratum: Medium effects on spin observables of proton knockout reactions PMID- 9970749 TI - Can one see Coulomb-nuclear interference effects in nucleon-nucleus scattering? PMID- 9970751 TI - Spectroscopy of 194Po. PMID- 9970752 TI - Signatures of multiphonon and neutron transfer couplings in the fusion of 36,32S+110Pd. PMID- 9970753 TI - Polarized proton capture by deuterium and the 2H(p, gamma )3He astrophysical S factor. PMID- 9970754 TI - Gamow-Teller strength in 54Fe and 56Fe. PMID- 9970755 TI - Spherical shell model description of rotational motion. PMID- 9970757 TI - Strangeness form factors of the nucleon and the anomalous magnetic moments of constituent quarks. PMID- 9970756 TI - Isospin nonequilibrium in heavy-ion collisions at intermediate energies. PMID- 9970759 TI - Pre-equilibrium particle emission and critical exponent analysis. PMID- 9970758 TI - Cold-fission yields at effective excitation energies. PMID- 9970760 TI - Neutron halo and spin-orbit splitting in some neutron-rich nuclei. PMID- 9970761 TI - Role of the rho meson in the nonmesonic hypernuclear decay. PMID- 9970762 TI - Measurements of Delta sigma T in polarized-neutron-polarized-proton scattering. PMID- 9970763 TI - Three-body correlations in few-body nuclei. PMID- 9970764 TI - Pion correlation from Skyrmion-anti-Skyrmion annihilation. PMID- 9970765 TI - Effects of meson-decay diagrams in proton-proton bremsstrahlung. PMID- 9970766 TI - Lifetime measurements of scissors mode excitations in 162,164Dy. PMID- 9970767 TI - Structural characteristics of 142Ce through inelastic neutron scattering. PMID- 9970768 TI - Damping of unbound single-particle modes. PMID- 9970769 TI - High-spin states and K-forbidden decay in 172Hf. PMID- 9970770 TI - Systematics of low-lying dipole strengths in odd and even Dy and Gd isotopes. PMID- 9970771 TI - Decay properties of the 02+ state and spin-parity assignments in 78Kr. PMID- 9970772 TI - Highly deformed band in 105Ag. PMID- 9970773 TI - Isospin-mixing corrections for fp-shell Fermi transitions. PMID- 9970775 TI - Gamow-Teller beta + decay of deformed nuclei near the proton drip line. PMID- 9970774 TI - beta decay of 11Li to the deuteron channel and halo analog states in 11Be. PMID- 9970776 TI - Chaoticity in vibrating nuclear billiards. PMID- 9970777 TI - Collisional damping in heated nuclei within the Landau-Vlasov kinetic theory. PMID- 9970778 TI - Large-basis shell model studies of light nuclei with a multivalued G-matrix effective interaction. PMID- 9970779 TI - Collisional damping of giant resonances in a non-Markovian approach. PMID- 9970781 TI - Systematic features of signature inversion of (h11/2)p(i13/2)n bands in doubly odd nuclei around A~160. PMID- 9970780 TI - Isovector response function of hot nuclear matter with Skyrme interactions. PMID- 9970782 TI - Systematic studies for medium-heavy even-even nuclei. PMID- 9970783 TI - Analyzing power measurements in pion-deuteron breakup at intermediate energies. PMID- 9970784 TI - Dipole excitations in p-shell nuclei via (p,n) reactions. PMID- 9970785 TI - Isomeric cross-section ratios for the formation of 75Gem,g in (n,p), (n, alpha ), and (n,2n) reactions from 6 to 15 MeV. PMID- 9970786 TI - Analyzing powers for the 2H(p PMID- 9970788 TI - Study of the reactions occurring in the fusion of 12C and 16O with heavy nuclei at incident energies below 10 MeV/nucleon. PMID- 9970787 TI - Simultaneous measurements of (p PMID- 9970789 TI - Photopion production from polarized nuclear targets. PMID- 9970791 TI - Vapor-liquid phase transition and multifragmentation of nuclei. PMID- 9970790 TI - Euclidean responses of 4He at high momentum transfer. PMID- 9970792 TI - Nonresonant breakup effects in 6Li PMID- 9970794 TI - Two-dimensional nuclear inertia: Analytical relationships. PMID- 9970793 TI - Analysis of the (N,xN') reactions by quantum molecular dynamics plus statistical decay model. PMID- 9970795 TI - Neutrons from multiplicity-selected Au-Au collisions at 150A, 250A, 400A, and 650A MeV. PMID- 9970796 TI - Fragmentation and multifragmentation of 10.6A GeV gold nuclei. PMID- 9970797 TI - Multiplicity distributions from central collisions of 16O+Cu at 14.6A GeV/c and intermittency. PMID- 9970798 TI - Search for pion-neutron bound states in 14.6A GeV Si + nucleus collisions. PMID- 9970799 TI - Baryon rapidity loss and midrapidity stacking in high energy nucleus-nucleus collisions. PMID- 9970800 TI - Extracting source parameters from Gaussian fits to two-particle correlations. PMID- 9970801 TI - Dilepton production in a chemically equilibrating, expanding, and hadronizing quark-gluon plasma. PMID- 9970802 TI - Causality violations in cascade models of nuclear collisions. PMID- 9970803 TI - Inhomogeneous nucleation of quark-gluon plasma in high energy nuclear collisions. PMID- 9970804 TI - Faddeev null-plane model of the nucleon. PMID- 9970806 TI - Self-consistent delta-hole model at nonzero temperature. PMID- 9970805 TI - Nucleon structure in a relativistic quark model. PMID- 9970808 TI - Absolute intensity of internal bremsstrahlung from the electron capture decay of 125I. PMID- 9970807 TI - Stellar neutron capture cross sections of the Gd isotopes. PMID- 9970809 TI - Two-proton correlations for 16O + 197Au collisions at E/A=200 MeV. PMID- 9970810 TI - Status of the Brueckner-Hartree-Fock approximation to the nuclear matter binding energy with the Paris potential. PMID- 9970811 TI - Composite nucleons in scalar and vector mean fields. PMID- 9970812 TI - Multiphonon structure in a gamma -unstable fermionic model. PMID- 9970813 TI - Sensitivity of quasielastic (p PMID- 9970814 TI - Quantum molecular dynamics and multistep-direct analyses of multiple preequilibrium emission. PMID- 9970815 TI - Local density functional for isovector-meson exchange. PMID- 9970816 TI - Comment on "Three-body resonances in 6He, 6Li, and 6Be, and the soft dipole mode problem of neutron halo nuclei" PMID- 9970817 TI - Reply to "Comment on 'Three-body resonances in 6He, 6Li, and 6Be, and the soft dipole mode problem of neutron halo nuclei' " PMID- 9970819 TI - Proton and neutron alignments in negative-parity bands of 76Kr. PMID- 9970818 TI - Lifetime measurements within the superdeformed minimum of 133Ce and 132Ce. PMID- 9970820 TI - Measurement of low mtK0s production from 14.6A GeV/c Si beams on a Pb target. PMID- 9970821 TI - Excited superdeformed band in 142Sm identical to 146Gd. PMID- 9970822 TI - Observation of strong isospin mixing in proton emission from the astrophysically interesting isobaric analog state in 23Mg. PMID- 9970823 TI - Low-spin termination of the superdeformed band in 135Nd. PMID- 9970824 TI - Pairing strength in neutron-rich isotopes of Zr. PMID- 9970825 TI - Identification of new nuclei at and beyond the proton drip line near the doubly magic nucleus 100Sn. PMID- 9970826 TI - Two-phonon character of the lowest J pi =1(-) state of 142Nd. PMID- 9970828 TI - Limiting temperatures of neutron rich nuclei: A possible interpretation of data from isotope yield ratios. PMID- 9970827 TI - Correlation between low-lying M1 and E2 strength in heavy rare earth nuclei. PMID- 9970829 TI - Neutron skin of nuclei near the neutron drip line. PMID- 9970831 TI - Direct radiative capture of p-wave neutrons. PMID- 9970830 TI - Statistical distribution of inertial parameters in normally deformed nuclei. PMID- 9970832 TI - Exact methods for expectation values in canonical fragmentation models. PMID- 9970833 TI - Changes in the n-p interaction strengths for Pd and Cd nuclei. PMID- 9970834 TI - Coplanar and noncoplanar nucleon-nucleon bremsstrahlung calculation: A study of pseudoscalar and pseudovector pi N couplings. PMID- 9970835 TI - Determination of the asymptotic D- to S-state ratio for 3He via (d PMID- 9970837 TI - Poincare invariant coupled channel model for the pion-nucleon system. PMID- 9970836 TI - Radiative capture of polarized neutrons by polarized protons at Tn=183 MeV. PMID- 9970838 TI - Precise solution of few-body problems with the stochastic variational method on a correlated Gaussian basis. PMID- 9970839 TI - Tensor analyzing power Ayy for dp breakup in the symmetric constant relative energy configuration. PMID- 9970840 TI - Neutral pion photoproduction on nuclei in baryon chiral perturbation theory. PMID- 9970841 TI - Repulsive short-range three-nucleon interaction. PMID- 9970842 TI - Hypernuclear weak decay of 12 Lambda C and 11 Lambda B. PMID- 9970843 TI - Band structures in 132Ba. PMID- 9970844 TI - Momentum distribution in nuclear matter and finite nuclei. PMID- 9970845 TI - Full-symmetry and mixed-symmetry states in even ruthenium isotopes. PMID- 9970846 TI - Favored noncollective oblate states in light tellurium isotopes. PMID- 9970847 TI - Microscopic study of a C4-symmetry hypothesis in A~150 superdeformed nuclei: Deformed Woods-Saxon mean field. PMID- 9970848 TI - sd-shell study with a multiconfiguration mixing approach designed for large scale nuclear structure calculations. PMID- 9970849 TI - Microscopic four-cluster description of the mirror nuclei 9Li and 9C. PMID- 9970850 TI - Proton momentum distribution in nuclei beyond 4He. PMID- 9970851 TI - Regular and chaotic motion in axially deformed nuclei. PMID- 9970852 TI - Density dependent hadron field theory. PMID- 9970853 TI - Tilted-axis cranking analysis in a simple model. PMID- 9970854 TI - Role of the breakup process in the 48Ca(20Ne,19Ne n) reaction at 48A MeV. PMID- 9970855 TI - Dynamics of heavy-ion fusion probed by d/p double ratios from a cross bombardment. PMID- 9970856 TI - Fusion l distribution in 16O, 28Si+115In reactions at near- and sub-barrier energies. PMID- 9970857 TI - Statistical analysis of correlated resonance phenomena in two systems: 28Si+20Ne and 24Mg+20Ne. PMID- 9970858 TI - Nuclear structure effects in the sub-barrier fusion of 16O + 70,72,73,74,76Ge. PMID- 9970859 TI - Mass and charge distributions for the reaction 40Ca + 209Bi at 600 MeV. PMID- 9970860 TI - Prompt and sequential decay processes in the fragmentation of 40 MeV/nucleon 20Ne projectiles. PMID- 9970862 TI - Prescission charged particle emission in 19F+232Th. PMID- 9970861 TI - Barrier distributions from the fusion of oxygen ions with 144,148,154Sm and 186W. PMID- 9970863 TI - Semiclassical and quantum mechanical analysis of the excitation function for the 130Te(p,n)130I reaction. PMID- 9970864 TI - Multifragment events in the 238U+197Au reaction at 15 MeV/nucleon. PMID- 9970865 TI - Fission fragment angular distributions for 11B and 19F+238U systems. PMID- 9970866 TI - Excitation of giant monopole resonance in 24Mg using 6Li scattering. PMID- 9970868 TI - Trajectory modifications in the Glauber model for heavy ions. PMID- 9970867 TI - Tensor analyzing powers for 7Li breakup. PMID- 9970869 TI - Fluctuations in nuclear fragmentation. PMID- 9970870 TI - Fully microscopic model analysis of the elastic and inelastic scattering of protons from 12C and for energies in the range 200 to 800 MeV. PMID- 9970871 TI - Delta degrees of freedom in antisymmetrized molecular dynamics and (p,p') reactions in the Delta region. PMID- 9970872 TI - Fusion cross section for the weakly bound neutron system 11Be+10Be at energies below and near the Coulomb barrier. PMID- 9970873 TI - Competing electric and magnetic excitations in backward electron scattering from heavy deformed nuclei. PMID- 9970874 TI - Fragmentation cross sections of relativistic 8436Kr and 10947Ag nuclei in targets from hydrogen to lead. PMID- 9970875 TI - Flavor production in Pb(160A GeV) on Pb collisions: Effect of color ropes and hadronic rescattering. PMID- 9970877 TI - Nuclear mesonic Cherenkov-like radiation from high energy nucleons. PMID- 9970876 TI - Baryon-antibaryon pair production in time-dependent meson fields. PMID- 9970878 TI - Valid QCD sum rules for vector mesons in nuclear matter. PMID- 9970879 TI - Generalized Nambu-Jona-Lasinio model in a study of the boson-exchange model of nuclear forces. PMID- 9970880 TI - QCD sum rules, scattering length, and vector mesons in the nuclear medium. PMID- 9970881 TI - Q2 dependence of nuclear shadowing. PMID- 9970883 TI - pi NN form factor from QCD sum rules. PMID- 9970882 TI - Baryon mapping of quark systems. PMID- 9970884 TI - Quark-quark potential from chiral symmetry. PMID- 9970886 TI - Shape of the beta spectra in the A=14 system. PMID- 9970885 TI - Exchange current corrections to neutrino-nucleus scattering. I. Nuclear matter. PMID- 9970887 TI - rho - omega mixing off shell and charge symmetry breaking in the N-N potential. PMID- 9970888 TI - Inclusive 12C( nu micro, micro)12N reaction in the continuum random phase approximation. PMID- 9970889 TI - Cross section of 36S(n, gamma )37S. PMID- 9970890 TI - Muon-induced neutron and pion production in an organic liquid scintillator at a shallow depth. PMID- 9970891 TI - Gamow-Teller strength distributions for nuclei in presupernova stellar cores. PMID- 9970893 TI - Astrophysical factor for the radiative capture reaction alpha +d-->6Li+ gamma. PMID- 9970892 TI - Strangeness in hadronic stellar matter. PMID- 9970894 TI - Correlation measurements of light charged particles emitted from 32S+27Al reactions at energies of 105 MeV and 215 MeV. PMID- 9970895 TI - Two-phonon gamma -vibrational state in 168Er. PMID- 9970896 TI - Weak strangeness production in nucleon-nucleon scattering. PMID- 9970897 TI - Nucleon helicity in pion photoproduction. PMID- 9970898 TI - Meson-mode mixing in the calculation of the nucleon-nucleon interaction. PMID- 9970899 TI - Existence of proton halos near the drip line. PMID- 9970901 TI - Low energy resonances in 15N( alpha, gamma )19F and 15O( alpha, gamma )19Ne. PMID- 9970900 TI - Erratum: Radiative decays of the 16.6 and 16.9 MeV states in 8Be and tests of the conservation of the vector current in the A=8 multiplet PMID- 9970902 TI - Evidence of massive cluster transfers in 19F+232Th reaction at near barrier energies. PMID- 9970903 TI - Fast electric dipole transitions in nuclei near N=82. PMID- 9970904 TI - Emission times for energy selected 1,2,3H ejectiles from central collisions: 1360 MeV 40Ar+Ag. PMID- 9970905 TI - Intruder bands in 114Te: Smooth band termination. PMID- 9970906 TI - Quantitative description of superdeformed bands with the projected shell model. PMID- 9970907 TI - Effect of Coulomb dipole polarizability of halo nuclei on their near-barrier fusion with heavy targets. PMID- 9970908 TI - Absolute pp-elastic cross sections from 492 to 793 MeV using CH2 targets. PMID- 9970909 TI - T20 measurements for 1H(d PMID- 9970910 TI - Total photoabsorption cross sections for 1H, 2H, and 3He from 200 to 800 MeV. PMID- 9970911 TI - Charge symmetry breaking effects in nucleon-nucleon scattering derived from the quark model. PMID- 9970912 TI - Scaling of three-body S-matrix poles. PMID- 9970913 TI - Nodal trajectories of spin observables and kaon photoproduction dynamics. PMID- 9970914 TI - Cascade calculation of K--p and K--d atoms. PMID- 9970915 TI - Nucleon- alpha -particle interactions from inversion of scattering phase shifts. PMID- 9970916 TI - [script l]-forbidden Gamow-Teller beta decay of 57Cu. PMID- 9970917 TI - beta + decay of 15.2-min 114Te. PMID- 9970919 TI - Magnetic dipole moment of 127Sb and 129Sb by nuclear magnetic resonance on oriented nuclei. PMID- 9970920 TI - Isovector M1 transitions in 28Si and the role of meson exchange currents. PMID- 9970918 TI - Superdeformation in bismuth. PMID- 9970921 TI - alpha -cluster states above the threshold energy in 44Ti. PMID- 9970923 TI - Average magnetic moments of pre-yrast high spin states in 166,165Hf. PMID- 9970922 TI - Band structure of the odd-even 125La, 127La nuclei. PMID- 9970924 TI - Dilepton decay from excited states in 28Si populated via different isospin entrance channels. PMID- 9970926 TI - Approximate particle number projection for finite range density dependent forces. PMID- 9970925 TI - Wave functions of the triaxial rotor model in the multiple "Q-excitation" scheme. PMID- 9970928 TI - Change of shape in the yrast sequence in 50Cr. PMID- 9970927 TI - Description of beta decay to excited quadrupole phonon states within a boson expansion formalism. PMID- 9970929 TI - Magnetic dipole transitions in superdeformed nuclei. PMID- 9970931 TI - Properties of proton drip-line nuclei at the sd-fp-shell interface. PMID- 9970930 TI - Hole spectral function and two-particle-one-hole response propagator. PMID- 9970932 TI - Light particle-evaporation residue coincidences for the 79Br+27Al system at 11.8 MeV/nucleon. PMID- 9970933 TI - Measurements of 65 MeV Fe, Sn, and Pb(n,n'x) continuum cross sections. PMID- 9970934 TI - Evaporation residue, fission cross sections, and linear momentum transfer for 14N induced reactions from 35A to 155A MeV. PMID- 9970935 TI - Delays associated with elementary processes in nuclear reaction simulations. PMID- 9970936 TI - Proton (neutron) spin rotation in a polarized nuclear target: Method for investigating nuclear interactions. PMID- 9970937 TI - Roper excitation in alpha -proton scattering. PMID- 9970939 TI - Extension of quantum molecular dynamics and its application to heavy-ion collisions. PMID- 9970938 TI - Analysis of parity violation in neutron resonances. PMID- 9970940 TI - Two and three nucleon induced photon absorption. PMID- 9970941 TI - Three-body reaction theory in a model space. PMID- 9970942 TI - Molecular states in the equator-equator orientation of two oblately deformed 12C nuclei. PMID- 9970943 TI - Theory of multiphonon excitation in heavy-ion collisions. PMID- 9970944 TI - Interactions of relativistic neon to nickel projectiles in hydrogen, elemental production cross sections. PMID- 9970946 TI - Quark model of phi coalescence from kaons in heavy-ion reactions. PMID- 9970945 TI - Search for fractionally charged nuclear fragments in relativistic heavy ion collisions. PMID- 9970947 TI - Coalescence of deuterons in relativistic heavy ion collisions. PMID- 9970949 TI - S-wave resonance coupled-channel approach to the reactions pi -+p--> eta +n and K +p--> eta + Lambda, and a determination of the eta n and eta Lambda scattering lengths. PMID- 9970948 TI - Off-mass-shell deformation of the nucleon structure function. PMID- 9970950 TI - Model gluon propagator and pion and rho -meson observables. PMID- 9970951 TI - Strange mesonic transition form factor. PMID- 9970953 TI - Updated resonance photodecay amplitudes to 2 GeV. PMID- 9970952 TI - Hadronization in the SU(3) Nambu-Jona-Lasinio model. PMID- 9970954 TI - Kaon-nucleon couplings for weak decays of hypernuclei. PMID- 9970955 TI - Charm production in flux tubes. PMID- 9970956 TI - Levels in 17C above the 16C+neutron threshold. PMID- 9970957 TI - Neutron capture cross section of 18O and its astrophysical implications. PMID- 9970958 TI - Direct neutron capture for magic-shell nuclei. PMID- 9970959 TI - New stellar reaction rates for 25Mg(p, gamma )26Al and 25Al(p, gamma )26Si. PMID- 9970960 TI - Study of the electronic rearrangement induced by nuclear transmutations: A B spline approach applied to the beta decay of 6He. PMID- 9970962 TI - Effect of bulk constants on the binding energy of neutron matter and beta stability of a neutron star. PMID- 9970961 TI - Reaction cross section in ultrarelativistic nuclear collisions. PMID- 9970963 TI - Distorted wave analyses of the 7Li( alpha,2 alpha )3H reaction. PMID- 9970964 TI - Why temperature-dependent fission barriers should not be included in statistical model calculations. PMID- 9970965 TI - alpha -cluster structure of the yrast bands of 44Ti. PMID- 9970967 TI - Hadron masses at finite density from the Zimanyi-Moskowski model. PMID- 9970966 TI - Unique determination of the tensor spin-spin part of the nucleon-nucleon forward scattering amplitude. PMID- 9970968 TI - Comment on "Role of heavy meson exchange in near threshold NN-->d pi " PMID- 9970969 TI - Search for p waves in low-energy proton capture reactions relevant to the solar neutrino problem. PMID- 9970970 TI - Reducibility and a new entropic term in multifragment charge distributions. PMID- 9970971 TI - The i13/2 proton intruder orbital in the superdeformed 193Tl nucleus: Effective magnetic moment and blocking of proton pairing. PMID- 9970973 TI - Energy dependence of fusion cross sections. PMID- 9970972 TI - Electron-positron pairs from thermal resonances in ultrarelativistic nuclear collisions. PMID- 9970974 TI - Pion charge exchange in the deuteron. PMID- 9970975 TI - Pion flow and antiflow in relativistic heavy-ion collisions. PMID- 9970976 TI - Structure of nonlocalities in meson exchange NN interactions and their role in the NN and 3N system. PMID- 9970978 TI - Leading-order nuclear pi - gamma exchange force. PMID- 9970977 TI - Quadrupole deformation of deuterons and final-state interaction in 2H PMID- 9970979 TI - Polarization observables in vector meson photoproduction. PMID- 9970981 TI - Spectroscopy of 20F levels. PMID- 9970980 TI - Nuclear moments of 179Ta from optical measurement of hyperfine structure. PMID- 9970982 TI - New search for 26O. PMID- 9970983 TI - Evidence for continuum E0 transitions following the decay of high spin states in 130Ce. PMID- 9970984 TI - Radioactivity of neutron deficient isotopes in the region N>82>Z. PMID- 9970985 TI - Evolution of collectivity to very high spins in 160Yb. PMID- 9970987 TI - Anomalous angular distributions in pion and alpha particle scattering to the 22+ state of 52Cr. PMID- 9970986 TI - Spectroscopy in the second well of the 148Gd nucleus: Two quasiparticle and collective excitations. PMID- 9970988 TI - Neutrinoless double beta decay within the quasiparticle random-phase approximation with proton-neutron pairing. PMID- 9970989 TI - Structure and reactions of the 12,14Be nuclei. PMID- 9970990 TI - Fermion dynamical symmetry model for the even-even and even-odd nuclei in the Xe Ba region. PMID- 9970991 TI - Neutron decay of high angular momentum states excited in transfer reactions. PMID- 9970992 TI - Structure of proton drip-line nuclei around doubly magic 48Ni. PMID- 9970993 TI - Selection rule for fragmentations of doorway s-hole states in light nuclei. PMID- 9970994 TI - Single-particle and collective properties of drip-line nuclei. PMID- 9970995 TI - Coupled-channels model for superdeformed prolate nuclei: alpha -chain states in 16O. PMID- 9970996 TI - Refined Thomas-Fermi description of hot nuclei. PMID- 9970997 TI - Tensor coupling and vector mesons in dense nuclear matter. PMID- 9970998 TI - Mass distribution in 19F induced fission of 232Th. PMID- 9970999 TI - Absence of isotopic dependence in the sub-barrier fusion of 48Ti+58,60,64Ni systems. PMID- 9971000 TI - Pion-nucleus single charge exchange induced by stopped negative pions. PMID- 9971001 TI - Resonant structures in the 20Ne+16O system. PMID- 9971002 TI - Dependence of intermediate mass fragment production on the reaction mechanism in light heavy-ion collisions at intermediate energy. PMID- 9971003 TI - Multi- PMID- 9971005 TI - Neutron elastic and inelastic breakup in reactions induced by 20Ne. PMID- 9971004 TI - Improvement of the nucleon emission process and the statistical property in molecular dynamics. PMID- 9971006 TI - Preequilibrium decay in the exciton model for nuclear potential with a finite depth. PMID- 9971007 TI - Scalar and vector interactions of a composite spin-1/2 system. PMID- 9971008 TI - Effects of shell structure and N/Z ratio of a projectile on the excitation energy distribution between interacting nuclei in deep-inelastic collisions. PMID- 9971009 TI - Nonexistence of the Oppenheimer-Phillips process in low-energy deuteron-nucleus collisions. PMID- 9971010 TI - Hadronization during quark-gluon plasma phase transition. PMID- 9971011 TI - Hanbury-Brown-Twiss analysis of anisotropic transverse flow. PMID- 9971012 TI - Comparisons between rescattering calculations and boson interferometry experiments. PMID- 9971013 TI - Cumulants, coherence, and contamination in multiparticle Bose-Einstein interferometry. PMID- 9971014 TI - Transverse momentum dependence of Hanbury-Brown-Twiss correlation radii. PMID- 9971015 TI - Study of time reversal violation in beta decay of polarized 8Li. PMID- 9971016 TI - Nuclear muon capture by 3He: Meson exchange currents for the triton channel. PMID- 9971017 TI - Neutron capture cross section of 15N at stellar energies. PMID- 9971018 TI - Low-lying levels in 57Cu and the rp process. PMID- 9971019 TI - High-spin results for 155Tb. PMID- 9971020 TI - Binary decay fragment cross sections and prescission charge multiplicity in 84Kr+27Al at 10.6 MeV/nucleon. PMID- 9971021 TI - Transition quadrupole moments in 84Zr. PMID- 9971022 TI - Analyzing powers for 1H PMID- 9971023 TI - g-factor measurement of 132Ba in the backbending region. PMID- 9971024 TI - Prescission neutron multiplicities and nuclear viscosity: A systematic study. PMID- 9971025 TI - Neutron halos and E1 resonances in 208Pb. PMID- 9971026 TI - Nuclear curvature energy in relativistic models. PMID- 9971027 TI - Low-lying magnetic dipole strength in 163Dy. PMID- 9971028 TI - Hyperon-accompanied fission with an incompletely equilibrated Lambda particle. PMID- 9971029 TI - Numerical convergence in solving the Vlasov equation. PMID- 9971030 TI - Comment on "Relativistic cluster dynamics of nucleons and mesons. II. Formalism and examples" PMID- 9971031 TI - Comment on "Shape and superdeformed structure in Hg isotopes in relativistic mean field model" and "Structure of neutron-deficient Pt, Hg, and Pb isotopes" PMID- 9971032 TI - Reply to "Comment on 'Shape and superdeformed structure in Hg isotopes in relativistic mean field model' and 'Structure of neutron-deficient Pt, Hg, and Pb isotopes' " PMID- 9971033 TI - Absence of entrance-channel effects in the high-energy gamma -ray emission from 146Gd. PMID- 9971034 TI - Spectroscopy of the halo nucleus 11Li by an experimental study of 11Li+p collisions. PMID- 9971036 TI - Reexamination of the nuclear orientation model of quasifission reactions to explain anomalous fragment anisotropies at sub-barrier energies. PMID- 9971035 TI - Superdeformation in 198Po. PMID- 9971037 TI - Do we have three S11 resonances in the second resonance region? PMID- 9971038 TI - Analysis of hard two-photon correlations measured in heavy-ion reactions at intermediate energies. PMID- 9971039 TI - Improved analysis of parity violation at neutron p-wave resonances of 238U based on resonance spin assignments. PMID- 9971040 TI - (e,e'p) reaction and the transition to the eikonal regime. PMID- 9971041 TI - Excess production of low-mass lepton pairs in S+Au collisions at the CERN Super Proton Synchrotron and the quark-hadron phase transition. PMID- 9971042 TI - One-proton halo in 26P and two-proton halo in 27S. PMID- 9971043 TI - Pion absorption on 3He at low energies. PMID- 9971044 TI - np-elastic analyzing power AN0 at 485 and 788 MeV. PMID- 9971045 TI - Bonn potential model at finite temperature. PMID- 9971046 TI - Consistent meson-field-theoretical description of pp bremsstrahlung. PMID- 9971047 TI - Multipole analysis of spin observables in vector meson photoproduction. PMID- 9971048 TI - Isospin-violating meson-nucleon vertices as an alternate mechanism of charge symmetry breaking. PMID- 9971049 TI - Two-pion exchange contributions to nuclear charge asymmetry. PMID- 9971050 TI - Quark delocalization, color screening, and N-N intermediate range attraction: P waves. PMID- 9971051 TI - Pion elastic and inelastic 21+ scattering on 58,60,62,64Ni at T pi =180 MeV. PMID- 9971052 TI - High-K isomers in 176W and mechanisms of K violation. PMID- 9971053 TI - Prompt gamma -ray spectroscopy of the 104Mo and 108Mo fission fragments. PMID- 9971055 TI - Structure and decay of a four-quasiparticle 15(-) isomer in 180Ta. PMID- 9971054 TI - Alpha-particle spectroscopic strengths in 19F and 20Ne. PMID- 9971056 TI - Spectroscopic study of Lambda 10B, Lambda 12C, Lambda 28Si, Lambda 89Y, Lambda 139La, and Lambda 208Pb by the ( pi +,K+) reaction. PMID- 9971058 TI - Dynamic realization of statistical state in finite systems. PMID- 9971057 TI - High spin states in 164Lu. PMID- 9971059 TI - Rearrangement of valence neutrons by proton excitation in odd-odd Sb nuclei. PMID- 9971060 TI - Green's function method with energy-independent vertex functions. PMID- 9971061 TI - Restoration of overlap functions and spectroscopic factors in nuclei. PMID- 9971062 TI - Transition charge densities at the onset of deformations for even-even 98-112Ru nuclei. PMID- 9971063 TI - Inelastic deuteron scattering from the high-spin isomer 178Hfm2 (16(+)). PMID- 9971064 TI - Angular distributions of gamma rays from the 7Li(p, gamma ) reaction at low energies. PMID- 9971065 TI - Inclusive positive pion photoproduction. PMID- 9971066 TI - Conclusive evidence for the influence of nuclear orientation on quasifission. PMID- 9971067 TI - Sub- and near-barrier reactions for 12C+108,110Pd and 7Li+113,115In. PMID- 9971068 TI - Triton and alpha-particle production in neutron-induced reactions on carbon at En=42.5, 62.7, and 72.8 MeV. PMID- 9971069 TI - Lattice gas model for fragmentation: From argon on scandium to gold on gold. PMID- 9971070 TI - Recurrence of the compound nucleus in neutron resonance reactions. PMID- 9971072 TI - Photon emission from a parton gas at chemical nonequilibrium. PMID- 9971071 TI - Uniform alpha -nucleus potential in a wide range of masses and energies. PMID- 9971073 TI - Determination of temperature and transverse flow velocity at chemical freeze-out in relativistic nuclear interactions. PMID- 9971074 TI - gKN Lambda and gKN Sigma from QCD sum rules. PMID- 9971075 TI - Nucleon-nucleon interaction in the chromodielectric soliton model: Dynamics. PMID- 9971077 TI - UA(1) breaking and scalar mesons in the Nambu and Jona-Lasinio model. PMID- 9971076 TI - Many-body theory of rho - omega mixing. PMID- 9971078 TI - Neutron capture cross sections of the cerium isotopes for s- and p-process studies. PMID- 9971079 TI - Charged current neutrino-nucleus reaction cross sections at intermediate energies. PMID- 9971080 TI - Hyperon-rich matter in neutron stars. PMID- 9971082 TI - Amplitude ambiguities in pseudoscalar meson photoproduction. PMID- 9971081 TI - Continuity equation in electron scattering from nuclei. PMID- 9971083 TI - Compressibility probed by linear momentum transfer. PMID- 9971085 TI - Comment on "Large-space shell-model calculations for light nuclei" PMID- 9971084 TI - Particle evaporation from semiclassical dynamics. PMID- 9971087 TI - Comment on "Energies and widths of low-lying levels in 11Be and 11N" PMID- 9971086 TI - Reply to "Comment on 'Large-space shell-model calculations for light nuclei' " PMID- 9971089 TI - Reply to "Comment on 'Okubo-Zweig-Iizuka rule violation in the reaction p-barp--> phi pi 0' " PMID- 9971088 TI - Comment on "Okubo-Zweig-Iizuka rule violation in the reaction p-barp--> phi pi 0" PMID- 9971090 TI - Reaction mechanisms in 12C( gamma,pp) near 200 MeV. PMID- 9971091 TI - Measurement of the 1H( gamma, pi 0) cross section near threshold. PMID- 9971092 TI - Cross comparisons of nuclear temperatures determined from excited state populations and isotope yields. PMID- 9971093 TI - Decreased absorption cross sections in the case of strongly coupled channels with positive Q values. PMID- 9971094 TI - Spinodal instabilities within the Boltzmann-Langevin approach. PMID- 9971095 TI - Rotational inertia of superdeformed nuclei: Intruder orbitals, pairing, and identical bands. PMID- 9971096 TI - Signature of diprotons in 3He( gamma PMID- 9971097 TI - Does the 3N force have a hard core? PMID- 9971098 TI - Chiral perturbation approach to the pp-->pp pi 0 reaction near threshold. PMID- 9971099 TI - Intermittency in 197Au fragmentation. PMID- 9971100 TI - Evolution of collectivity in 82Y and 82Sr. PMID- 9971101 TI - Rotational high spin structures in doubly-odd 184Au. PMID- 9971102 TI - Half-life of 130Te double- beta decay measured with geologically qualified samples. PMID- 9971103 TI - High-spin states in 121,122Te: Identification of favored noncollective oblate states. PMID- 9971104 TI - Gd isotope systematics with Skyrme and delta -pairing forces. PMID- 9971105 TI - Extended vector meson dominance model for the baryon octet electromagnetic form factors. PMID- 9971106 TI - Searching for three-nucleon resonances. PMID- 9971108 TI - Effects of short-range correlations on Ca isotopes. PMID- 9971107 TI - Shell-model picture of virtual detour transitions in 41Ca radiative electron capture decay. PMID- 9971110 TI - Quartets reexamined. PMID- 9971109 TI - Dynamic shape asymmetry in soft nuclei. PMID- 9971111 TI - Broken pairs in the interacting boson model: Projection of spurious states. PMID- 9971113 TI - Subthreshold internal conversion to bound states in highly ionized 125Te ions. PMID- 9971112 TI - Microscopic description of E2 and E3 giant resonances in deformed and superdeformed nuclei. PMID- 9971114 TI - Multiphonon theory: Wick's theorem and recursion formulas for coupled phonons. PMID- 9971115 TI - Further application of a semimicroscopic core-particle coupling method to the properties of 155,157Gd and 159Dy. PMID- 9971116 TI - Effective gamma deformation near A=130 in the interacting boson model. PMID- 9971117 TI - Momentum distribution in nuclear matter within a perturbation approximation. PMID- 9971119 TI - Calculation of the A=184 F-spin multiplet. PMID- 9971118 TI - Thermostatic properties of semi-infinite polarized nuclear matter. PMID- 9971120 TI - Realistic model of the nucleon spectral function in few- and many-nucleon systems. PMID- 9971121 TI - Test of a density-dependent interaction using in-plane 28Si(p PMID- 9971122 TI - Reaction 13C(n,p)13B at 65 MeV. PMID- 9971123 TI - Differential cross sections of the 12,13C(p,p)12,13C and 12,13C(p,n)12,13N reactions near 180 degrees. PMID- 9971124 TI - Entrance-channel effects in quasifission reactions. PMID- 9971125 TI - Reaction and total cross sections for low energy pi + and pi - on isospin zero nuclei. PMID- 9971126 TI - Fragmentation of 78Kr projectiles. PMID- 9971127 TI - Nonstatistical gamma emission in 3He- and alpha -induced reactions. PMID- 9971128 TI - Polarization transfer in inelastic proton scattering from 4(-) states in 16O at 350 MeV. PMID- 9971129 TI - Nuclear stopping in heavy-ion collisions at 100 MeV/nucleon from inclusive and exclusive neutral pion measurements. PMID- 9971130 TI - (p,d) reaction on 62Ni at 65 MeV. PMID- 9971132 TI - Cavitation and penetration in central collisions with light ions. PMID- 9971131 TI - Evidence for a highly deformed band in 16O+16O breakup of 32S. PMID- 9971133 TI - Neutron pair and proton pair transfer reactions between identical cores in the sulfur region. PMID- 9971134 TI - Nucleon-induced preequilibrium reactions in terms of the quantum molecular dynamics. PMID- 9971135 TI - Statistical simultaneous multifragmentation model for heavy ion collisions with entrance channel characteristics. PMID- 9971136 TI - Thermal fission rate around superfluid-normal phase transition. PMID- 9971137 TI - Description of sub-barrier heavy ion fusion in a semiclassical quantum tunneling model. PMID- 9971138 TI - Quasielastic scattering in the inclusive (3He, t) reaction. PMID- 9971139 TI - Collective friction coefficients in the relaxation time approximation. PMID- 9971140 TI - Incomplete-fusion-fragmentation model: Multifragmentation data from 600A MeV heavy-ion collisions. PMID- 9971141 TI - Dynamical analysis of the evolution of nuclear density modes. PMID- 9971143 TI - Color singlet suppression of quark-gluon plasma formation. PMID- 9971142 TI - One- and two-dimensional multifractals in proton-AgBr interactions at 800 GeV. PMID- 9971144 TI - Hadron-nuclear collisions. PMID- 9971145 TI - Expansion, thermalization, and entropy production in high-energy nuclear collisions. PMID- 9971147 TI - Temperature and density effects on the nucleon mass splitting. PMID- 9971146 TI - Properties of strangelets at finite temperature in the liquid drop model. PMID- 9971148 TI - Delta decay in the nuclear medium. PMID- 9971149 TI - Pion-nucleon and kaon-nucleon scattering lengths in QCD sum rules. PMID- 9971150 TI - Bosonization in the presence of confinement: Calculation of the nucleon-nucleon interaction. PMID- 9971151 TI - Constraining 26Al+p resonances using 26Al(3He,d)27Si. PMID- 9971152 TI - Astrophysical reaction rate for the 18F(p, alpha )15O reaction. PMID- 9971153 TI - First evidence for excited states in 101In. PMID- 9971154 TI - Squeeze-out of nuclear matter in Au+Au collisions. PMID- 9971155 TI - Search for 16O+16O+16O structure in 48Cr. PMID- 9971156 TI - The reaction d( alpha, gamma )6Li at low energies and the primordial nucleosynthesis of 6Li. PMID- 9971157 TI - Upper limit of the lifetime of 16B. PMID- 9971159 TI - Low-energy polarized-proton capture on 6Li. PMID- 9971158 TI - Measurement of the polarization transfer parameter DNN for 12,13C(p PMID- 9971160 TI - Stripping of two protons and one- alpha -particle transfer reactions for 16O+ASm and their influence on the fusion cross section. PMID- 9971162 TI - Macroscopic features of light heavy-ion fission reactions. PMID- 9971161 TI - Stretched alignment due to pairing correlation between the normal and abnormal parity orbits for the gamma -soft nuclei in the light rare-earth region. PMID- 9971163 TI - Total cross sections for K+ scattering on light nuclei. PMID- 9971164 TI - Test of shell-model interactions for nuclear structure calculations. PMID- 9971166 TI - Poles of the S matrix for a complex potential. PMID- 9971165 TI - Feeding of hole states by proton decay of Gamow-Teller and isobaric analog state resonances. PMID- 9971167 TI - Momentum distributions in stripping reactions of single-nucleon halo nuclei. PMID- 9971169 TI - Analysis of alpha -particle emission from 19F +181Ta reactions leading to residues. PMID- 9971168 TI - Antibaryons in massive heavy ion reactions: Importance of potentials. PMID- 9971170 TI - Reply to "Analysis of alpha -particle emission from 19F+181Ta reactions leading to residues" PMID- 9971171 TI - Comment on "Double-octupole excitations in the N=84 nuclei 144Nd and 146Sm" PMID- 9971172 TI - Reply to "Comment on 'Double octupole excitations in the N=84 nuclei 144Nd and 146Sm' " PMID- 9971173 TI - Erratum: Energy variation of nuclear level density in 104Pd and 114Sn in the excitation-energy region of 7 to 24 MeV PMID- 9971174 TI - Decay from a superdeformed band in 194Pb. PMID- 9971175 TI - New isomer 32Alm. PMID- 9971176 TI - Impact parameter dependence of the disappearance of transverse flow in nuclear collisions. PMID- 9971178 TI - Correlations in the in-medium nucleon-nucleon cross section. PMID- 9971177 TI - Fusionlike reactions of 40Ar up to 1.36 GeV: Prethermalization and postthermalization particles and fragments. PMID- 9971179 TI - Nonlocal nature of the nuclear force and its impact on nuclear structure. PMID- 9971181 TI - Low energy strength in low-multipole response function of nuclei near the neutron drip line. PMID- 9971180 TI - Relativistic analysis of the 208Pb(e,e'p)207Tl reaction at high momentum. PMID- 9971182 TI - Zero-crossing angle of the n-p analyzing power. PMID- 9971184 TI - Three-body model study of A=6-7 hypernuclei: Halo and skin structures. PMID- 9971183 TI - Reactions pd-->3He eta and pd-->3He pi + pi - near the eta threshold. PMID- 9971185 TI - Two-nucleon potential from chiral Lagrangians. PMID- 9971186 TI - Effects of intruder states in 179Ir. PMID- 9971187 TI - Alignment additivity in the two-quasiparticle superdeformed bands of 192Tl. PMID- 9971188 TI - High spin states in 68As: Experiment and theory. PMID- 9971190 TI - Level structure of 216At. PMID- 9971189 TI - Magnetic moments of 17N and 17B. PMID- 9971191 TI - Nuclear structure calculations in the density-dependent relativistic Hartree theory. PMID- 9971192 TI - Effect of isospin mixing on superallowed Fermi beta decay. PMID- 9971193 TI - Semiclassical interpretation of an M1 sum rule derived within the interacting boson model. PMID- 9971194 TI - Higher order long range correlations in nuclear structure and dynamics. PMID- 9971195 TI - Nucleon spectral function at finite temperature and the onset of superfluidity in nuclear matter. PMID- 9971196 TI - Description of superdeformed nuclei in the interacting boson model. PMID- 9971197 TI - Where is the non-spin-flip isovector monopole resonance in 208Tl? PMID- 9971198 TI - Spectroscopic factors for nucleon knock-out from 16O at small missing energy. PMID- 9971199 TI - Microscopic structure of high-spin vibrational excitations in superdeformed 190,192,194Hg. PMID- 9971200 TI - Identical bands at normal deformation: Necessity of going beyond the mean-field approach. PMID- 9971201 TI - Natural orbitals, overlap functions, and mean-field orbitals in an exactly solvable A-body system. PMID- 9971202 TI - Unified picture of the BCS nuclear model by use of the 1/N expansion. PMID- 9971204 TI - Size effect in the deexcitation of hot nuclei. PMID- 9971203 TI - Inclusive electron scattering from nuclei at x~=1. PMID- 9971205 TI - Giant dipole resonance in very hot nuclei of mass A PMID- 9971207 TI - Deuteron breakup at extreme forward angles: Failure of a pure Coulomb dissociation description. PMID- 9971206 TI - Changing source characteristics during multifragment decay. PMID- 9971209 TI - Electron-nucleon cross section in (e,e'p) reactions. PMID- 9971208 TI - Coulomb breakup mechanism of neutron-halo nuclei in a time-dependent method. PMID- 9971210 TI - Effective inertial coefficient for the dinuclear regime of the exotic decay of nuclei. PMID- 9971211 TI - Angular correlations in internal pair conversion of aligned heavy nuclei. PMID- 9971212 TI - Two-nucleon model calculation of (p, pi -) spectra for calcium isotopes. PMID- 9971214 TI - Inversion solution to heavy-ion optical model potential at intermediate energies. PMID- 9971213 TI - Modified three-body full-folding optical model potential. PMID- 9971215 TI - Statistical properties of antisymmetrized molecular dynamics for non-nucleon emission and nucleon-emission processes. PMID- 9971217 TI - Neural networks for impact parameter determination. PMID- 9971216 TI - Real part of the heavy-ion optical potential derived from relativistic mean field theory. PMID- 9971219 TI - Dilepton production from resonance scattering in hot hadronic matter. PMID- 9971218 TI - Soft photons from relativistic heavy ion collisions. PMID- 9971220 TI - Microscopic relativistic model for deuteron-nucleus scattering. PMID- 9971221 TI - Strangeness conservation constraints in hadron gas models. PMID- 9971222 TI - 1/Nc expansion of the quark condensate at finite temperature. PMID- 9971223 TI - Nuclear suppression of hadroproduction. PMID- 9971224 TI - Low-energy QCD: Chiral coefficients and the quark-quark interaction. PMID- 9971225 TI - Unitary, gauge invariant, relativistic resonance model for pion photoproduction. PMID- 9971227 TI - Delta excitations in neutrino-nucleus scattering. PMID- 9971226 TI - Stability analysis of the instantaneous Bethe-Salpeter equation and the consequences for meson spectroscopy. PMID- 9971228 TI - Moxon-Rae setup for the measurement of stellar (n, gamma ) rates and the example of 87Rb. PMID- 9971229 TI - Determination of the 9Be( alpha,n)12C reaction rate. PMID- 9971230 TI - Astrophysical reaction rates for 10B(p, alpha )7Be and 11B(p, alpha )8Be from a direct model. PMID- 9971231 TI - Strange neutral currents in nuclei. PMID- 9971232 TI - alpha -decay properties of 181Pb. PMID- 9971234 TI - Yrast band in neutron-deficient 115Xe. PMID- 9971233 TI - Octupole excitations in the N=85 lanthanides. PMID- 9971235 TI - U(6/20) supersymmetry in 115-119Sn isotopes. PMID- 9971236 TI - E2 transition and QJ+ systematics of even mass palladium nuclei. PMID- 9971237 TI - Equivalent photon approach to simultaneous excitation in heavy ion collision. PMID- 9971238 TI - Effects of nuclear Coulomb field on two-meson correlations. PMID- 9971239 TI - Energy of the first excited state of 9B. PMID- 9971240 TI - Incompressibility of nuclear matter, and Coulomb and volume-symmetry coefficients of nucleus incompressibility in the relativistic mean field theory. PMID- 9971241 TI - Limit on T-violating P-conserving rho NN interaction from the gamma decay of 57Fe. PMID- 9971242 TI - Interacting boson model basis and Hamiltonian for Delta L=4 staggering. PMID- 9971243 TI - K0 form factor and charge radius in a covariant Salpeter model. PMID- 9971244 TI - Chaos vs linear instability in the Vlasov equation: A fractal analysis characterization. PMID- 9971245 TI - Erratum: alpha -d capture with formation of 6Li and the isoscalar E1 multipole PMID- 9971246 TI - Low-energy pionic double charge exchange on the beta beta -instable nuclei 128,130Te. PMID- 9971247 TI - Nonperturbative treatment of gluons and pseudoscalar mesons in baryon spectroscopy. PMID- 9971248 TI - Quasibound states of eta -nucleus systems. PMID- 9971250 TI - Electromagnetic production of associated strangeness. PMID- 9971249 TI - What does a change in the quark condensate say about restoration of chiral symmetry in matter? PMID- 9971251 TI - Integral equation calculations for the photodisintegration process 4He( gamma,n)3He. PMID- 9971253 TI - pp-->pp pi 0 reaction near threshold: A chiral power counting approach. PMID- 9971252 TI - Isospin invariance and the spin structure of the amplitude for the process 3H+3He ->d2H+4He. PMID- 9971254 TI - High-K structure in 77As. PMID- 9971255 TI - High-spin states in 107Pd, 108Pd, and 109Ag. PMID- 9971256 TI - Configurations of superdeformed bands in 193Pb. PMID- 9971257 TI - Low-lying Gamow-Teller states in 92Nb. PMID- 9971258 TI - Isospin character of low-lying states in 56Fe. PMID- 9971259 TI - Gamma-ray transitions in 206Pb studied in the 205Pb(n, gamma ) reaction. PMID- 9971260 TI - Study of nuclear shapes in Tl isotopes via excited state giant dipole resonance studies in the reaction 16O+181Ta. PMID- 9971261 TI - Systematics of low-lying dipole excitations in the deformed even-even nuclei 164,166,168,170Er. PMID- 9971262 TI - Smooth band termination in 108Sn. PMID- 9971263 TI - Spin-parity assignments and evidence for mixed-symmetry states in 100Ru. PMID- 9971264 TI - Lipkin-Nogami pairing scheme in self-consistent nuclear structure calculations. PMID- 9971265 TI - Quantum Monte Carlo diagonalization with angular momentum projection. PMID- 9971267 TI - Relativistic Hamiltonians in many-body theories. PMID- 9971266 TI - M1 properties of tungsten isotopes in the interacting boson model-2. PMID- 9971268 TI - Mean-field description of ground-state properties of drip-line nuclei: Pairing and continuum effects. PMID- 9971269 TI - Cluster model of alpha decay and 212Po. PMID- 9971270 TI - g boson and systematics of the M1 scissors mode. PMID- 9971271 TI - E3 transition probabilities in the platinum, mercury, and lead isotopes. PMID- 9971272 TI - Analyzing powers in 4He(6Li PMID- 9971273 TI - Elastic and inelastic scattering of 16O+64Zn at near-barrier energies. PMID- 9971274 TI - Angular correlations for alpha -particle decay in the reaction 12C PMID- 9971275 TI - Isomeric cross-section ratio for the formation of 58Com,g in neutron, proton, deuteron, and alpha-particle induced reactions in the energy region up to 25 MeV. PMID- 9971276 TI - Spontaneous fission properties of 104262Rf. PMID- 9971277 TI - Sub-barrier transfer reactions in 58Ni+162Dy. PMID- 9971278 TI - Relative and absolute neutron-induced fission cross sections of 208Pb, 209Bi, and 238U in the intermediate energy region. PMID- 9971279 TI - Reaction cross sections for 38, 65, and 97 MeV deuterons on targets from 9Be to 208Pb. PMID- 9971280 TI - Orbiting features in the strongly damped binary decay of the 28Si+16O system. PMID- 9971281 TI - Self-consistent relativistic Boltzmann-Uehling-Uhlenbeck equation for the Delta distribution function. PMID- 9971282 TI - Adiabatic treatment of final states in (p,d*) reactions. PMID- 9971284 TI - 12C+12C and 16O+12C potentials by inversion. PMID- 9971283 TI - Antisymmetrized molecular dynamics of wave packets with stochastic incorporation of the Vlasov equation. PMID- 9971285 TI - Calculations for 4He(e,e'N). PMID- 9971287 TI - Resonance phenomena near thresholds. PMID- 9971286 TI - Study of the decay of hot nuclei formed in 139La-induced reactions at E/A = 45 MeV by a hybrid dynamical-statistical calculation. PMID- 9971288 TI - Sensitivity of reaction cross sections to halo nucleus density distributions. PMID- 9971289 TI - Cold fission as cluster decay with dissipation. PMID- 9971290 TI - Mean field calculations of nucleon-nucleus scattering. PMID- 9971291 TI - Pauli forbidden states and the alpha +14C optical potential. PMID- 9971292 TI - High-multiplicity lead-lead interactions at 158 GeV/c per nucleon. PMID- 9971293 TI - J/ psi suppression in an equilibrating parton plasma. PMID- 9971294 TI - Equation of state of an interacting pion gas with realistic pi - pi interactions. PMID- 9971295 TI - Transport coefficients of a hot pion gas. PMID- 9971296 TI - QCD scales in finite nuclei. PMID- 9971297 TI - Brueckner correlations following a boson mapping of the two-color delta model. PMID- 9971298 TI - Relativistic Hamiltonian dynamics of pions in nucleons. PMID- 9971299 TI - Scaling for deuteron structure functions in a relativistic light-front model. PMID- 9971300 TI - Detection of atmospheric neutrinos and relativistic nuclear structure effects. PMID- 9971301 TI - Importance of (n,p) reactions for stellar beta decay rates. PMID- 9971302 TI - Direct reaction calculation of the 11Li Coulomb dissociation spectrum. PMID- 9971303 TI - Isomers in 94Rh. PMID- 9971304 TI - Use of quark wave functions in the calculation of structure functions of mesons. PMID- 9971306 TI - Momentum distributions of particles from three-body halo fragmentation: Final state interactions. PMID- 9971305 TI - Mean-field calculations of quasielastic responses in 4He. PMID- 9971307 TI - Comment on "Prolate-oblate band mixing and new bands in 182Hg" PMID- 9971308 TI - Reply to "Comment on 'Prolate-oblate band mixing and new bands in 182Hg' " PMID- 9971309 TI - Isotopic identification of the parity-violating neutron p-wave resonance at energy E0=3.2 eV in Xe. PMID- 9971311 TI - Multiple dipole bands at prolate shapes in 136Nd and their description through the projected shell model. PMID- 9971310 TI - Observation of a large parity nonconserving analyzing power in Xe. PMID- 9971312 TI - Enhanced E0 and E2 transition rates in the midshell Xe isotopes. PMID- 9971313 TI - Evidence of initial state interactions in multinucleon pion absorption. PMID- 9971315 TI - Sub-Coulomb dissociation of 8B. PMID- 9971314 TI - Origin of slow, heavy residues observed in dissipative 197Au+86Kr collisions at E/A=35 MeV. PMID- 9971316 TI - Effective gA in the pf shell. PMID- 9971317 TI - Excess electron pairs from heavy-ion collisions at CERN and a more complete picture of thermal production. PMID- 9971318 TI - Theoretical predictions for pionium searches. PMID- 9971319 TI - Coherent electroproduction of pions from 3He. PMID- 9971320 TI - Evidence for large discrepancies between data and calculations for the kinematically incomplete neutron-deuteron breakup reaction. PMID- 9971321 TI - Coulomb-Sturmian separable expansion approach: Three-body Faddeev calculations for Coulomb-like interactions. PMID- 9971322 TI - Excited states in 139Sm described with the interacting boson model plus broken pairs. PMID- 9971323 TI - High energy octupole resonance in 116Sn. PMID- 9971324 TI - Nuclear structure of 170Tm from neutron-capture and (d,p)-reaction measurements. PMID- 9971325 TI - Shell-model influence in the rotational nucleus 86Mo. PMID- 9971326 TI - The (7Li, 7Be gamma ) reaction and isovector spin strength in 40Ca. PMID- 9971328 TI - Universal predictions for statistical nuclear correlations. PMID- 9971327 TI - Structure of the mirror nuclei 9Be and 9B in a microscopic cluster model. PMID- 9971329 TI - Angular-momentum cranking applied to multiphonon anharmonic collective vibrations: Cranked bifurcation theory. PMID- 9971330 TI - Systematic behavior of octupole states in deformed rare earth nuclei and the interacting boson approximation. PMID- 9971331 TI - Anharmonicities of gamma vibrations in odd-mass deformed nuclei. PMID- 9971332 TI - Multinucleon transfer reactions in 40Ca+124Sn. PMID- 9971333 TI - Observation of cold fission in 242Pu spontaneous fission. PMID- 9971334 TI - Role of quasideuteron absorption in the 6Li( pi +, pp) reaction at T pi +=100, 165 MeV. PMID- 9971335 TI - Cross section for the 103Rh(n,n')103Rhm reaction in the energy range 5.7-12 MeV. PMID- 9971337 TI - 12C(p,n)12N reaction at 135 MeV. PMID- 9971336 TI - 35Cl+12C asymmetrical fission excitation functions. PMID- 9971338 TI - Competition among the decay modes of projectile remnants in (600 MeV/nucleon) Au + Cu reactions. PMID- 9971339 TI - Isotopic yields for the cold fission of 252Cf. PMID- 9971340 TI - 4He fragments from the 14N + 12C collision at 35 MeV/nucleon and clustering in colliding nuclei. PMID- 9971341 TI - Clustering recognition model for intermediate energy heavy ion reactions. PMID- 9971342 TI - Analysis of proton-induced fragment production cross sections by the quantum molecular dynamics plus statistical decay model. PMID- 9971343 TI - New single particle basis for microscopic description of decay processes. PMID- 9971345 TI - Elastic scattering of a halo nucleus in the relativistic mean field theory. PMID- 9971344 TI - Superasymmetric two-center shell model for spontaneous heavy-ion emission. PMID- 9971346 TI - Nonlocal effects in a semiclassical WKB approach to sub-barrier nuclear fusion processes. PMID- 9971347 TI - Determination of nuclear friction in strongly damped reactions from prescission neutron multiplicities. PMID- 9971348 TI - Antiproton-nucleus elastic and inelastic scattering at intermediate energies. PMID- 9971349 TI - Modeling cluster production at the BNL Alternating Gradient Synchrotron. PMID- 9971350 TI - Field-theoretical description of nuclear matter with only the pion-nucleon interaction. PMID- 9971351 TI - Quark-meson coupling model for finite nuclei. PMID- 9971352 TI - Parity violation in charged-particle resonance reactions. PMID- 9971353 TI - Measurement of 7Li(n, gamma 0)8Li cross sections at En=1.5-1340 eV. PMID- 9971354 TI - Determination of the thermal neutron induced 36Cl(n,p)36S and 36Cl(n, alpha )33P reaction cross sections. PMID- 9971355 TI - Analysis of the total 12C( alpha, gamma )16O cross section based on available angular distributions and other primary data. PMID- 9971356 TI - Standard neutrino spectrum from 8B decay. PMID- 9971357 TI - Precision measurement of the half-life of 7Be. PMID- 9971358 TI - Excited superdeformed band in 131Ce. PMID- 9971359 TI - First-order eikonal approximation for the elastic scattering of 800 MeV/c pions from 12C and 40Ca nuclei. PMID- 9971360 TI - Core-polarization effects in pion single-charge-exchange reaction on p-shell nuclei. PMID- 9971361 TI - Structure of the dynamical polarization potential. PMID- 9971362 TI - Comment on "Very weak gamma transitions in the epsilon / beta + decay of 68Ga" PMID- 9971363 TI - Reply to "Comment on 'Very weak gamma transitions in the epsilon / beta + decay of 68Ga' " PMID- 9971364 TI - Complete valence particle yrast lines in N=84 nuclei above gadolinium. PMID- 9971365 TI - Quasifree pi + production studied using the 12C( gamma, pi +n)11B reaction in the Delta (1232) resonance region. PMID- 9971366 TI - 40Ca+40Ca reaction at Elab=35 MeV/nucleon: Filters and signatures to distinguish nearly central from peripheral collisions. PMID- 9971367 TI - Strangelet search and light nucleus production in relativistic Si+Pt and Au+Pt collisions. PMID- 9971369 TI - Double- Lambda hypernuclear formation via a neutron-rich Xi state. PMID- 9971368 TI - Identification of 166Pt and 167Pt. PMID- 9971370 TI - Early fragment formation in heavy-ion collisions. PMID- 9971371 TI - Measurements of the total cross section for the scattering of polarized neutrons from polarized 3He. PMID- 9971372 TI - Calculation of the nucleon-nucleon interaction due to vector-meson exchange. PMID- 9971373 TI - Comparison of instant form and front form one-particle exchange models. PMID- 9971374 TI - Relativistic bound-state equations in three dimensions. PMID- 9971375 TI - Three-body calculation of 9Be electromagnetic observables. PMID- 9971376 TI - Theoretical study of the radiative capture reactions 2H(n, gamma )3H and 2H(p, gamma )3He at low energies. PMID- 9971377 TI - Measurement of the nuclear magnetic moments of 57Ni and 59Fe. PMID- 9971378 TI - Collective and quasiparticle excitations in superdeformed 190Hg. PMID- 9971379 TI - Identification of gamma transitions in 147Ba, 149Ce, and 151,153Nd. PMID- 9971380 TI - First spectroscopic study of 22Si. PMID- 9971381 TI - 97Tc produced by the (3He,pn gamma ) reaction. PMID- 9971382 TI - One-nucleon transfer reactions to continuum states induced by heavy ion projectiles. PMID- 9971383 TI - Gamow-Teller strength to 38K from the 38Ar(p,n) reaction and 38Ca( beta +) decay. PMID- 9971384 TI - Triaxial bands in 133Ce. PMID- 9971386 TI - High-spin states and signature inversion in 78Br. PMID- 9971385 TI - alpha decay of 273110: Shell closure at N=162. PMID- 9971387 TI - Application of a semimicroscopic core-particle coupling method to the backbending in odd deformed nuclei. PMID- 9971388 TI - Femtometer toroidal structures in nuclei. PMID- 9971389 TI - Evidence for a weaker isovector potential. PMID- 9971390 TI - Neutron halos in the Na isotopes. PMID- 9971391 TI - Is there experimental evidence for an interpretation of the lowest K=0 collective excitation of deformed nuclei as a phonon excitation of the gamma band? PMID- 9971392 TI - Nonperturbative derivation of non-Hermitian and Hermitian effective interactions and operators. PMID- 9971393 TI - Spin M1 excitations in deformed nuclei from self-consistent Hartree-Fock plus random-phase approximation. PMID- 9971394 TI - Dissipative shape dynamics in the sd shell. PMID- 9971395 TI - Systematic study of spin assignments and signature inversion of pi h11/2 PMID- 9971396 TI - Hadrodynamic approach to compressible nonuniform nuclear systems. PMID- 9971397 TI - 4 pi studies of the 1.8-4.8 GeV 3He+natAg, 197Au reactions. I. Energy deposition. PMID- 9971399 TI - Fission before K equilibration. PMID- 9971398 TI - 4 pi studies of the 1.8-4.8 GeV 3He+natAg, 197Au reactions. II. Multifragmentation. PMID- 9971400 TI - Fusion and transfer reactions in the 19F+165Ho system at energies near the Coulomb barrier. PMID- 9971402 TI - S-matrix analysis of heavy-ion elastic scattering. PMID- 9971401 TI - Inclusive (p, alpha ) reactions on 27Al, 59Co, and 197Au at incident energies of 120, 160, and 200 MeV. PMID- 9971403 TI - Fusion systematics in the barrier region using the neutron flow model. PMID- 9971405 TI - Local approximations to the exchange nonlocality for neutron-16O scattering. PMID- 9971404 TI - Many-body Coulomb perturbation of azimuthal alpha - alpha correlations. PMID- 9971407 TI - Light fragment emission during mass asymmetry relaxation in heavy-ion induced fission. PMID- 9971406 TI - Solution of the Bethe-Goldstone equation with an exact propagator. PMID- 9971408 TI - Effects of systematic errors in analyses of nuclear scattering data. PMID- 9971409 TI - Contribution of density fluctuations to the damping of giant resonances. PMID- 9971410 TI - pt dependence of transverse flow in relativistic heavy-ion collisions. PMID- 9971412 TI - Cold strangelets formation with finite size effects in high energy heavy-ion collisions. PMID- 9971411 TI - Initial and final state effects in the charmonium suppression in hadron-nucleus and nucleus-nucleus collisions. PMID- 9971413 TI - Realistic expanding source model for invariant one-particle multiplicity distributions and two-particle correlations in relativistic heavy-ion collisions. PMID- 9971414 TI - Production of antiprotons in the upper atmosphere by interacting primary cosmic rays. PMID- 9971415 TI - Ioffe current constant from a relativistic three quark model. PMID- 9971417 TI - Virtual Compton scattering off the nucleon at low energies. PMID- 9971416 TI - Polarized deep-inelastic scattering from nuclei: A relativistic approach. PMID- 9971418 TI - Role of color neutrality in nuclear physics: Modifications of nucleonic wave functions. PMID- 9971420 TI - Search for a 2485-keV gamma ray in 208Pb with the inelastic neutron scattering reaction. PMID- 9971419 TI - Neutrino trapping in nonstrange dense stellar matter. PMID- 9971421 TI - Octupole correlations in neutron rich, odd-A lanthanum nuclei. PMID- 9971422 TI - Determination of the 190Po alpha reduced width. PMID- 9971423 TI - Projectile Delta excitations in 1H(p,n)N pi reactions. PMID- 9971424 TI - Nontrivial aspects of the onset of nuclear collectivity: Static moments. PMID- 9971425 TI - Erratum: First evidence for excited states in 101In PMID- 9971426 TI - Direct proof of the two-phonon character of the dipole excitations in 142Nd and 144Sm around 3.5 MeV. PMID- 9971427 TI - Superdeformation below N=73. PMID- 9971428 TI - Configuration changes and hindered decays in four- and six-quasiparticle isomers in 178Ta. PMID- 9971429 TI - From criticality to supercooling in expanding hot nuclear matter: Possible explanation of low- tau puzzle. PMID- 9971430 TI - Magnetic moments of C isotopes studied with antisymmetrized molecular dynamics. PMID- 9971431 TI - Nuclear temperature of the disassembling source in central heavy-ion collisions from isotope yields. PMID- 9971433 TI - Bethe-Salpeter amplitudes and static properties of the deuteron. PMID- 9971432 TI - Effective T-odd P-even hadronic interactions from quark models. PMID- 9971435 TI - Mass and width of the d' resonance in nuclei. PMID- 9971434 TI - Deuteron electromagnetic form factors in the intermediate energy region. PMID- 9971437 TI - Measurements of nuclear magnetic moments and electric quadrupole moments of Lu isotopes. PMID- 9971438 TI - Transition strengths and new band structures in odd-odd 78Rb. PMID- 9971436 TI - High spin states in 175Ta: An acute example of delayed crossing frequency. PMID- 9971439 TI - Lifetime measurements of strongly deformed rotational bands in 133Pm. PMID- 9971440 TI - Structure of the neutron-halo nucleus 6He. PMID- 9971441 TI - Yrast gamma -ray spectroscopy of the neutron rich isotopes 61,63Co. PMID- 9971442 TI - Additional results from the beta -delayed proton decays of 27P and 31Cl. PMID- 9971444 TI - Decays of the 97Y isomers to the single neutron nucleus 97Zr. PMID- 9971443 TI - Shears bands in 193Pb. PMID- 9971446 TI - Spontaneous symmetry breaking and the dissipation of nuclear collective degrees of freedom at finite temperature. PMID- 9971445 TI - Measurements for spin inversion and noninversion in successive decays via nuclear magnetic resonance on oriented nuclei. PMID- 9971447 TI - Thermodynamical properties and Coulomb instabilities in hot nuclear systems with the Gogny interaction. PMID- 9971449 TI - Skyrme-Hartree-Fock calculation on He, Li, and Be isotopes. PMID- 9971448 TI - Two-nucleon spectral function of 16O at high momenta. PMID- 9971450 TI - Systematics of first and second shape transition temperatures in heavy nuclei. PMID- 9971452 TI - Simple model of neutron "halo nuclei" PMID- 9971451 TI - alpha decay as a probe for phase transitions in nuclei. PMID- 9971453 TI - Decay out of superdeformed bands in the A PMID- 9971454 TI - Relativistic N-body models. PMID- 9971455 TI - Double charge exchange on Te isotopes in the generalized seniority scheme. PMID- 9971456 TI - Dynamic effective potential for alpha -particle bound and quasibound states. PMID- 9971458 TI - Thermal and microcanonical treatments of a pairing Hamiltonian. PMID- 9971457 TI - Shapes of odd-odd Pr nuclei. PMID- 9971459 TI - Stability of proton-rich nuclei in the upper sd shell and lower pf shell. PMID- 9971461 TI - Quasielastic scattering of 9Li on 12C. PMID- 9971460 TI - Fission decay of 48Cr at ECN* PMID- 9971463 TI - One and two charge stripping reactions in the 12C+197Au and 16O+197Au systems at large distances. PMID- 9971462 TI - 6Li-vector+12C inelastic scattering at 30 and 50 MeV. PMID- 9971464 TI - Excitation energy division in heavy-ion reactions. PMID- 9971466 TI - Supersymmetry between deep and shallow optical potentials for 16O+16O scattering. PMID- 9971465 TI - Five-nucleon simultaneous and sequential transfer in the 12C(11B,6Li)17O and 12C(d,7Li)7Be reactions. PMID- 9971468 TI - Total reaction cross section calculations in proton-nucleus scattering. PMID- 9971467 TI - Exclusive (e,e'p) reaction at high missing momenta. PMID- 9971469 TI - Shape dependence of single particle response and the one body limit of damping of multipole vibrations of a cavity. PMID- 9971470 TI - New precompound decay model. PMID- 9971472 TI - Shell-like structures in an expanding quark-antiquark plasma. PMID- 9971473 TI - Bremsstrahlung production of low mass dielectrons in relativistic heavy ion collisions. PMID- 9971471 TI - Medium effects on binary collisions with the Delta resonance. PMID- 9971474 TI - Collective radial expansion in Au+Au reactions from 0.25 to 2 GeV/nucleon. PMID- 9971475 TI - Hydrodynamical analysis of symmetric nucleus-nucleus collisions near 200A GeV. PMID- 9971476 TI - Bose-Einstein correlations for three-dimensionally expanding, cylindrically symmetric, finite systems. PMID- 9971478 TI - Gauge invariance and confinement in a generalized Nambu-Jona-Lasinio model. PMID- 9971477 TI - Quantum-mechanical equivalent-photon spectrum for heavy-ion physics. PMID- 9971479 TI - Unitary ambiguity in the extraction of the E2/M1 ratio for the gamma N Delta transition. PMID- 9971480 TI - Modified quark-meson coupling model for nuclear matter. PMID- 9971481 TI - Ambiguities in the partial-wave analysis of pseudoscalar-meson photoproduction. PMID- 9971482 TI - Role of tensor meson pole and Delta exchange diagrams in pp-bar--> pi + pi - PMID- 9971483 TI - Stellar neutron capture cross sections of the tin isotopes. PMID- 9971484 TI - Resonance neutron capture and transmission measurements and the stellar neutron capture cross sections of 134Ba and 136Ba. PMID- 9971485 TI - Weak gamma -transition intensities in the electron capture decay of 144Pm. PMID- 9971487 TI - Ground-state energies and widths of 5He and 5Li nuclei. PMID- 9971486 TI - Low lying states in 153Ho and 157Tm from electron capture and beta + decay of 153Er and 157Yb. PMID- 9971488 TI - Beyond the Dirac-Brueckner-Hartree-Fock model: Equation of state and occupation probabilities of the Bonn potential. PMID- 9971489 TI - Collision broadening of the rho meson in a dropping mass scenario. PMID- 9971490 TI - Comment on "Strangeness enhancement in p+A and S+A interactions at energies near 200A GeV" PMID- 9971491 TI - Reply to "Comment on 'Strangeness enhancement in p+A and S+A interactions at energies near 200A GeV' " PMID- 9971492 TI - Erratum: Role of the rho meson in the nonmesonic hypernuclear decay PMID- 9971493 TI - Multiple superdeformed bands in 132Nd. PMID- 9971494 TI - Source size scaling of fragment production in projectile breakup. PMID- 9971495 TI - Disappearance of entrance channel dependence of fission fragment anisotropies at well-above-barrier energies. PMID- 9971496 TI - Measurement of the longitudinal analyzing power for noncoplanar p-d breakup. PMID- 9971497 TI - Cross-section measurements for the 2H(p,n)2p reaction at 135 MeV. PMID- 9971499 TI - Solving the four-dimensional NN- pi NN equations for scalars below the meson production threshold. PMID- 9971498 TI - Measurement of T20(90 degrees) in the 1H(d PMID- 9971500 TI - pi NN and pi N Delta form factors determined from a microscopic model for pi N scattering. PMID- 9971501 TI - Nucleon-antinucleon interaction from the Skyrme model. PMID- 9971502 TI - Pauli principle in the soft-photon approach to proton-proton bremsstrahlung. PMID- 9971503 TI - Search for hyperdeformation in 146,147Gd. PMID- 9971505 TI - First observation of nonyrast levels in 103Zr and level systematics of N = 63 Sr, Zr, and Mo isotones. PMID- 9971504 TI - Is there a bound dineutron in 11Li? PMID- 9971506 TI - Smooth termination of intruder bands in 51109Sb. PMID- 9971507 TI - Single-particle states in 66149Dy83 at high spin. PMID- 9971508 TI - Self-consistent calculations of Be isotopes. PMID- 9971509 TI - Path integral variational methods for strongly correlated systems. PMID- 9971510 TI - Realistic shell-model calculations for neutron deficient Sn isotopes. PMID- 9971511 TI - Realistic collective nuclear Hamiltonian. PMID- 9971512 TI - 114Ru in axial and nonaxial microscopic frameworks. PMID- 9971513 TI - Strength functions and spreading widths of simple shell model configurations. PMID- 9971514 TI - Nearest neighbor spacing distributions of low-lying levels of vibrational nuclei. PMID- 9971515 TI - Radial flow in 40Ar+45Sc reactions at E=35-115 MeV/nucleon. PMID- 9971516 TI - Total hadronic photoabsorption cross section on nuclei in the nucleon resonance region. PMID- 9971517 TI - Total reaction and 2n-removal cross sections of 20-60A MeV 4,6,8He, 6-9,11Li, and 10Be on Si. PMID- 9971518 TI - Isospin dependence of intermediate mass fragment production in heavy-ion collisions at E/A=55 MeV. PMID- 9971519 TI - Limitation of the fusion cross section for the 12C+11B system at Ec.m.=36.5 and 41.7 MeV. PMID- 9971521 TI - Differential cross sections for neutrino scattering on 12C. PMID- 9971520 TI - The d PMID- 9971522 TI - Reaction mechanism coexistence in the 123 MeV 19F+56Fe reaction. PMID- 9971523 TI - Inclusive (p,p') reactions on nuclei in the mass range 115 to 181 at incident energies from 120 to 200 MeV. PMID- 9971524 TI - Quasideuteron effect with a polarized gamma PMID- 9971525 TI - 0f7/2 proton transfer on 55Mn. PMID- 9971527 TI - Nuclear fission beyond two-body kinematics. PMID- 9971526 TI - 8B proton halo via reaction and breakup cross section measurements. PMID- 9971528 TI - Excited halo nuclear state and long range interaction in nuclear reactions. PMID- 9971529 TI - Kaon photoproduction near threshold and their coupling constants. PMID- 9971530 TI - Inverse scattering for a specific resonating group model nonlocality. PMID- 9971531 TI - Antiprotonic studies of nuclear neutron halos. PMID- 9971532 TI - Radii of halo nuclei from cross section measurements. PMID- 9971533 TI - Relations between fusion cross sections and average angular momenta. PMID- 9971534 TI - Large basis shell model analysis of 14N( gamma, pi +)14Cg.s. reaction. PMID- 9971535 TI - Structure signatures in proton scattering from 9,11Li. PMID- 9971536 TI - Observables in high-statistics measurements of the reaction p-barp--> Lambda -bar Lambda. PMID- 9971537 TI - Two-particle rapidity correlations in C+Ta interactions at 4.2A GeV/c. PMID- 9971538 TI - Characteristics of charged particle multiplicities distribution in relativistic heavy-ion interactions. PMID- 9971539 TI - Lambda flow in heavy-ion collisions: The role of final-state interactions. PMID- 9971540 TI - Dilepton production in ultrarelativistic heavy-ion collisions. PMID- 9971541 TI - Low transverse momentum photon production in proton-nucleus collisions at 18 GeV/c. PMID- 9971542 TI - Measurement of the pi +p PMID- 9971543 TI - Electromagnetic form factors in a collective model of the nucleon. PMID- 9971545 TI - eta -deuteron scattering. PMID- 9971544 TI - Probing nucleon strangeness with neutrinos: Nuclear model dependences. PMID- 9971546 TI - Renormalized quasiparticle random phase approximation and double beta decay: A critical analysis of double Fermi transitions. PMID- 9971547 TI - 12C( alpha, gamma )16O cross sections at stellar energies. PMID- 9971548 TI - Structure of 18Ne and the breakout from the hot CNO cycle. PMID- 9971549 TI - Measurement of neutron capture on 48Ca at thermal and thermonuclear energies. PMID- 9971550 TI - Causality in dense matter. PMID- 9971551 TI - Neutrino mean free path in asymmetric nuclear matter at high density. PMID- 9971552 TI - Mass dependence of fragment anisotropy in the fission of 11B+237Np and 16O+209Bi systems. PMID- 9971553 TI - Observation of fine structure in 190Pb alpha decay. PMID- 9971554 TI - alpha decay of a new isotope 209Th. PMID- 9971555 TI - Cross sections for 45Sc(p,2n)44Ti and related reactions. PMID- 9971556 TI - Neutron resonances in 166Ho. PMID- 9971557 TI - Quasicontinuum ridges in 173,174W. PMID- 9971558 TI - Monopole transfer strength to 132,134Ba in (p,t) reactions and the interacting boson approximation. PMID- 9971559 TI - Alpha decays of neutron deficient isotopes in the region N >~ 82 >~ Z. PMID- 9971560 TI - Final state charge exchange interactions in the 12C(e,e'p) reaction. PMID- 9971561 TI - Nucleon mean free path in nuclear matter in a density-dependent sigma - omega model. PMID- 9971562 TI - Occupation probability of harmonic-oscillator quanta for microscopic cluster model wave functions. PMID- 9971563 TI - Two mode, finite range distorted wave Born approximation analysis of the 9Be(p, alpha )6Li reaction at 45 and 50 MeV. PMID- 9971564 TI - Intermittent and multifractal behaviors of multiplicity distributions in 800 GeV p-nucleus interactions. PMID- 9971565 TI - Does the quark cluster model predict a JP=0(-) isospin-2 dibaryon resonance? PMID- 9971566 TI - Comment on "Continuum Tamm-Dancoff approximation calculations for the escape widths of the isobaric analog state and Gamow-Teller resonance in 208Bi" PMID- 9971567 TI - Reply to "Comment on 'Continuum Tamm-Dancoff approximation calculations for the escape widths of the isobaric analog state and Gamow-Teller resonance in 208Bi' " PMID- 9971568 TI - Erratum: Sum rules in the proton-neutron interacting boson model: Generalized treatment and specific applications PMID- 9971569 TI - Study of the unbound nucleus 11N by elastic resonance scattering. PMID- 9971571 TI - Spatial separation of outer neutrons in 11Li. PMID- 9971570 TI - Viscosity and fission time scale of 156Dy. PMID- 9971572 TI - 3He( gamma,pp)n cross sections with tagged photons below the Delta resonance energy. PMID- 9971574 TI - Light-front pion exchange in elastic electron-deuteron scattering. PMID- 9971573 TI - Effective meson-exchange potentials in the SU6 quark model for NN and YN interactions. PMID- 9971575 TI - pi rho correlations in the NN potential. PMID- 9971576 TI - Two-pion-exchange potential and the pi N amplitude. PMID- 9971577 TI - Validity of certain soft photon amplitudes. PMID- 9971579 TI - First observation of mixed-symmetry states in a good U(5) nucleus. PMID- 9971578 TI - Superdeformed structures in 197,198Pb. PMID- 9971580 TI - Excited levels in 145Pm. PMID- 9971581 TI - New levels in 168Er: Use of a Compton-suppressed Ge array with the (n, gamma ) reaction. PMID- 9971582 TI - Systematic study of the fragmentation of low-lying dipole strength in odd-A rare earth nuclei investigated in nuclear resonance fluorescence experiments. PMID- 9971583 TI - Coulomb-nuclear interference with alpha particles in the excitation of the 2(+)1 states in 100,102,104Ru. PMID- 9971585 TI - Measurement of the hyperfine anomaly between 187Os and 189Os. PMID- 9971584 TI - alpha decay of 216Fr and 212At. PMID- 9971586 TI - Doppler-shift attenuation method lifetime measurements of low-lying states in 111In. PMID- 9971587 TI - pi h11/2 intruder and pi g9/2-1 strongly coupled bands in 115Sb. PMID- 9971588 TI - Self-consistent velocity dependent effective interactions. PMID- 9971589 TI - Geometrical interpretation of the semimicroscopic algebraic cluster model. PMID- 9971591 TI - "Bare" single-particle energies in 56Ni. PMID- 9971590 TI - Triaxiality in quadrupole deformed nuclei. PMID- 9971592 TI - Core polarization charges of quadrupole transitions in neutron drip line nuclei. PMID- 9971594 TI - Hartree-Fock-Bogoliubov approximation to relativistic nuclear matter. PMID- 9971593 TI - Shapes and stability within the interacting boson model: Dynamical symmetries. PMID- 9971596 TI - Isotopic shifts of odd-A Rb isotopes in the relativistic mean field approach. PMID- 9971595 TI - Generator coordinate method calculation of the E2 decay lifetime of shape isomers in the actinide region. PMID- 9971597 TI - Analyzing power measurements for 209Bi(n,n) at 6 and 9 MeV and consistent dispersive optical-model analyses for n+209Bi and n+208Pb from -20 to +80 MeV. PMID- 9971599 TI - Searching for the nuclear liquid-gas phase transition in Au+Au collisions at 35 MeV/nucleon. PMID- 9971598 TI - High energy gamma -ray production from Be, C, and Al targets with 65 MeV 3He bombardment. PMID- 9971600 TI - Total cross section and resonance spectroscopy for n+124Sn. PMID- 9971601 TI - Momentum dependence of the nuclear mean field from peripheral heavy-ion collisions. PMID- 9971602 TI - Resonance spin assignments in 12C+12C(3(-)) inelastic scattering from angular correlation methods. PMID- 9971603 TI - Fission of heavy nuclei induced by stopped antiprotons. II. Correlations between fission fragments. PMID- 9971604 TI - Evidence for one-pion charge exchange in 13N + 13C elastic scattering near the Coulomb barrier. PMID- 9971606 TI - Statistical kinetic approach to nuclear liquid-gas phase transition. PMID- 9971605 TI - Single-nucleon transfer to unbound states by means of the 4He( alpha,3He)5He reaction at 158 and 200 MeV. PMID- 9971607 TI - Parametrization of pion-nucleon phase shifts and effects upon pion-nucleus scattering calculations. PMID- 9971608 TI - Elastic and inelastic scattering of 1.37 GeV alpha particles from 12C and 40,42,44,48Ca. PMID- 9971609 TI - Approximate treatment of electron Coulomb distortion in quasielastic (e,e') reactions. PMID- 9971611 TI - Nuclear surface localization of preequilibrium reactions at low energies. PMID- 9971610 TI - Relativistic Thomas-Fermi description of collective modes in droplets of nuclear matter. PMID- 9971612 TI - Nuclear transparency to intermediate-energy protons. PMID- 9971613 TI - Double-folding interaction for 6He + alpha scattering. PMID- 9971614 TI - Sensitivity of nucleon-nucleus scattering to the off-shell behavior of on-shell equivalent NN potentials. PMID- 9971615 TI - Simulated Bose-Einstein correlations in multiplicity distributions from relativistic heavy-ion collisions. PMID- 9971616 TI - Thermal and chemical equilibration in relativistic heavy ion collisions. PMID- 9971617 TI - Quark-hadron phase transition with surface fluctuations. PMID- 9971619 TI - Coherent pion effects at large rapidities in nucleus-nucleus collisions. PMID- 9971618 TI - Lepton production from charm decay in nuclear collisions at sqrt s=200 GeV and 5.5 TeV per nucleon. PMID- 9971620 TI - Baryons as solitonic solutions of the chiral sigma model. PMID- 9971621 TI - Light and heavy mesons in the context of the quasipotential equation. PMID- 9971622 TI - Meson-exchange model for pi N scattering and gamma N--> pi N reaction. PMID- 9971624 TI - Internal bremsstrahlung spectrum of 139Ce. PMID- 9971625 TI - Observables in muon capture on 23Na and the effective weak couplings g-tildea and g-tildep. PMID- 9971623 TI - Evidence for neutrino oscillations from muon decay at rest. PMID- 9971626 TI - Neutron capture resonances in 116Sn, 118Sn, and 120Sn. PMID- 9971627 TI - Neutrino induced transitions between the ground states of the A=12 triad. PMID- 9971628 TI - Superfluid densities in neutron-star matter. PMID- 9971629 TI - Magnetically catalyzed fusion. PMID- 9971630 TI - First observation of beta decay of 108Nb to 108Mo. PMID- 9971631 TI - Superdeformed band in 147Tb. PMID- 9971633 TI - High spin states in 109Sn. PMID- 9971632 TI - Reaction 13C(n,p)13B at 118 MeV. PMID- 9971634 TI - Analytical study of factorial moments for first- and second-order phase transitions. PMID- 9971635 TI - gamma n--> pi -p process in 4He and 16O. PMID- 9971636 TI - Comment on "Analysis of hard two-photon correlations measured in heavy-ion reactions at intermediate energies" PMID- 9971637 TI - Erratum: gamma -ray transitions in 206Pb studied in the 205Pb(n, gamma ) reaction PMID- 9971638 TI - Measurement of the 1H(6He,6Li)n reaction in inverse kinematics. PMID- 9971639 TI - Test of Delta I=2 staggering in the superdeformed bands of 194Hg. PMID- 9971640 TI - Emission of intermediate mass fragments during fission. PMID- 9971641 TI - Dynamic shape effect in 126Ba at low spin. PMID- 9971642 TI - Compton scattering, meson exchange, and the polarizabilities of bound nucleons. PMID- 9971643 TI - Observation of the 1(+) scissors mode in the gamma -soft nucleus 134Ba. PMID- 9971644 TI - Cosmic ray measurement of the 54Mn beta - partial half-life. PMID- 9971645 TI - Search for Delta (1232)-resonance excitation in heavy-ion collisions around 100 MeV/nucleon. PMID- 9971646 TI - Spectral line shape of exotic nuclei. PMID- 9971647 TI - Simple formula for E(4(+)1)-E(2 1+) correlations and the magnification of structural anomalies. PMID- 9971648 TI - Backbending in 50Cr. PMID- 9971649 TI - mperp dependence of Bose-Einstein correlation radii. PMID- 9971650 TI - Antikaon flow in heavy-ion collisions: Effects of absorption and mean-field potential. PMID- 9971651 TI - Secondary decays and the helium lithium isotope thermometer. PMID- 9971652 TI - What information can we obtain from the yield ratio pi -/ pi + in heavy-ion collisions? PMID- 9971653 TI - Kaon production via gamma N-->K Sigma in the chiral quark model. PMID- 9971654 TI - Investigation of nuclear charge symmetry by pion elastic scattering from 3H and 3He. PMID- 9971655 TI - Measurement of the p-barp--> Lambda -bar Lambda and p-barp--> Sigma -bar 0 Lambda +c.c. reactions at 1.726 and 1.771 GeV/c. PMID- 9971656 TI - Pionic-decay spectra of few-body Lambda hypernuclei. PMID- 9971657 TI - Soft two-meson-exchange nucleon-nucleon potentials. I. Planar and crossed-box diagrams. PMID- 9971658 TI - Soft two-meson-exchange nucleon-nucleon potentials. II. One-pair and two-pair diagrams. PMID- 9971659 TI - Meson-baryon-baryon vertex function and the Ward-Takahashi identity. PMID- 9971660 TI - Neutron-rich isotopes 54-57Ti. PMID- 9971661 TI - Lifetime and g-factor measurements of the 11(-) isomer in 92Tc. PMID- 9971662 TI - Favored neutron excitations in superdeformed 147Gd. PMID- 9971663 TI - Spectroscopy of the 29Si(p, gamma ) reaction for Ep=1.75-2.51 MeV. PMID- 9971664 TI - gamma decay from states at low excitation energy in the neutron-deficient isotope, 200Rn, identified by correlated radioactive decay. PMID- 9971665 TI - Levels of 105Pd populated in the decay of 105Agm,g and comparison with interacting boson-fermion model calculations. PMID- 9971667 TI - Spreading width of the isobaric analog state and isospin mixing. PMID- 9971666 TI - Excited states in neutron-deficient 198Bi. PMID- 9971669 TI - Properties of Delta I=4 bifurcation from the projected shell model. PMID- 9971668 TI - Continuum random phase approximation method applied to the inclusive transverse electron scattering response. PMID- 9971670 TI - Systematic study of nuclear beta decay. PMID- 9971672 TI - Persisting alpha -planar structure in 20Ne. PMID- 9971671 TI - No-core shell-model calculations with starting-energy-independent multivalued effective interactions. PMID- 9971673 TI - Interplay between one-body and collisional damping of collective motion in nuclei. PMID- 9971675 TI - Delta excitations in compressed finite nuclei. II. Nucleon-nucleon interaction dependence. PMID- 9971674 TI - Regularity and chaos in Vlasov evolution of nuclear matter. PMID- 9971676 TI - Breakup reactions of the halo nuclei 11Be and 8B. PMID- 9971677 TI - Preequilibrium processes in the fusion of 12C with 103Rh up to 20 MeV/nucleon. PMID- 9971678 TI - Classical tests for statistical evaporation at 680 MeV 40Ar+natAg. PMID- 9971679 TI - Scaling laws in 3He induced nuclear fission. PMID- 9971680 TI - Fusion barrier distributions for heavy ion systems involving prolate and oblate target nuclei. PMID- 9971681 TI - Angular distributions for the 12C( gamma,p)11B reaction. PMID- 9971682 TI - Collisions between 48Ti + 93Nb at 917 MeV. PMID- 9971684 TI - Coupled channels analysis of high precision fusion data. PMID- 9971683 TI - Intermediate mass fragments emission in the reaction 96 MeV 19F on 12C. PMID- 9971685 TI - Angular distributions for knockout and scattering of protons in the eikonal approximation. PMID- 9971686 TI - Polarization observables in the process d+p-->d+X and electromagnetic form factors of N-->N* transitions. PMID- 9971687 TI - Energy dependent potentials determined by inversion: The p+ alpha potential up to 65 MeV. PMID- 9971689 TI - Effect of nuclear absorption on nucleon transfer probabilities in heavy-ion reactions. PMID- 9971688 TI - Relationship between ground state and double analog cross sections in pion double charge exchange. PMID- 9971690 TI - Meson exchange currents in the 3He( gamma, pi +)3H reaction. PMID- 9971691 TI - Determination of in-medium nucleon-nucleon cross sections from the data of proton induced reaction cross sections. PMID- 9971692 TI - Effect of nuclear shape of neutron rich isotopes in heavy ion reactions. PMID- 9971693 TI - Target and projectile fragmentations in 208Pb-emulsion collisions at 160A GeV. PMID- 9971694 TI - Nuclear dependence of single-hadron and dihadron production in p-A interactions at sqrt s=38.8 GeV. PMID- 9971695 TI - Entropy production by resonance decays. PMID- 9971696 TI - Anisotropic transverse flow and the Hanbury-Brown-Twiss correlation function. PMID- 9971697 TI - Pion electromagnetic form factor at finite temperature. PMID- 9971698 TI - Covariant diquark-quark model of the nucleon in the Salpeter approach. PMID- 9971699 TI - Determination of pion-baryon coupling constants from QCD sum rules. PMID- 9971700 TI - Axial current conservation in the Bethe-Salpeter approach to the nuclear two-body problem. PMID- 9971701 TI - Gamow-Teller strength of 26Mg. PMID- 9971702 TI - Population of the 283 keV level of 137Ba by the beta decay of 137Cs. PMID- 9971704 TI - Distribution of electrons over final states in beta decay of atomic tritium beyond the shakeoff approximation. PMID- 9971703 TI - Compound-nucleus contributions to 6Li+12C scattering. PMID- 9971706 TI - Kaon dispersion relation and flow in relativistic heavy-ion collisions. PMID- 9971707 TI - Optical model approach for heavy ion fusion. PMID- 9971705 TI - Two-particle-one-hole excitations in the continuum. PMID- 9971708 TI - Entrance-channel mass-asymmetry dependence of compound nucleus formation time in light heavy-ion reactions. PMID- 9971710 TI - Anomalous transverse distribution of pions as a signal for the production of disoriented chiral condensates. PMID- 9971709 TI - Photoexcitation mechanisms investigated through the fission channel. PMID- 9971711 TI - Time scale of the preequilibrium process in intermediate-energy nucleon-induced reactions. PMID- 9971712 TI - Core contribution to the nuclear magnetic quadrupole moment. PMID- 9971713 TI - Accuracy of calculating the exchange part of the real alpha-nucleus potential. PMID- 9971714 TI - Comment on "Multinucleon mechanisms in ( gamma,N) and ( gamma,NN) reactions" PMID- 9971715 TI - Reply to "Comment on 'Multinucleon mechanisms in ( gamma,N) and ( gamma,NN) reactions' " PMID- 9971716 TI - First observation of excited states in 192Po. PMID- 9971717 TI - Production and identification of new neutron-rich nuclei, 31Ne and 37Mg, in the reaction 80A MeV 50Ti+181Ta. PMID- 9971718 TI - Superdeformed band in 155Dy: Where does the "island" of superdeformation end? PMID- 9971719 TI - Laser ionization of 124Ag and its decay to levels of 124Cd. PMID- 9971721 TI - Temperature determination from the lattice gas model. PMID- 9971720 TI - Valence correlation scheme for single nucleon separation energies. PMID- 9971722 TI - Perception of discrimination and ethnocultural variables in a diverse group of adolescents. AB - Despite current interest in the multi-dimensionality of culture and ethnicity there are few studies that have explored the role of discrimination with ethnocultural variables. In this study social identity theory was used as a framework to test the relation between discrimination and components of ethnic identity, and attitudes towards out-groups. A school-based survey in a large south-west metropolitan area in 1994 was undertaken with students (n=3071) of African-American, European-American, Mexican-American, and Vietnamese-American descent using multiple measures of ethnicity. Hierarchical multiple regression results indicated that two components of ethnic identity played different roles in the relation between discrimination and attitudes towards others. Consistent with social identity theory, results indicated that perception of more discrimination was predicted by high ethnic exploration, and having more negative attitudes towards out-groups. However, ethnic affirmation, which is a positive sense of belonging to one's ethnic group, was only indirectly related to discrimination through attitudes toward others. In fact, contrary to social identity theory, a stronger sense of belonging to one's group was associated with more positive attitudes toward out-groups. Results have important implications for race relations. PMID- 9971723 TI - Knowledge, attitudes and behaviours related to HIV and AIDS among chinese adolescents in hong kong. AB - The purpose of this study was to assess HIV and AIDS knowledge and attitudes, source of HIV and AIDS information, and behaviours related to HIV and AIDS among Chinese adolescents in Hong Kong. Participants included 1259 (826 females and 433 males) Chinese adolescents in Hong Kong between 12-18 years of age. Findings revealed that over 80% of the adolescents had rarely or never discussed HIV and AIDS with their family or teacher, and the primary source of HIV and AIDS information was media sources such as television and newspapers. Findings revealed HIV and AIDS misinformation among both male and female adolescents in the areas of transmission, facts, personal vulnerability and attitudes. However, participants reported engaging in little at-risk behaviour associated with HIV and AIDS. Implications for HIV and AIDS education and prevention are discussed. PMID- 9971724 TI - Subtypes of stalking (obsessional following) in adolescents. AB - Stalking, which has been given the clinical term "obsessional following", is repetitive threatening or harassing behavior that creates a fear of harm in the victim. Empirical and theoretical literature on this form of behavior is beginning to develop and focuses primarily on adults. Three major subtypes of obsessional following have been identified: erotomania, love obsessional, and simple obsessional/borderline erotomania. Using this typology and available empirical research, a context is set in which three cases of adolescent obsessional following are discussed and analysed. These cases document that stalking/obsessional following occurs in adolescents and that important similarities and differences appear to exist between adult and adolescent offenders. Hypotheses are generated to encourage further study of this significant problem. PMID- 9971725 TI - Love and dating experience in early and middle adolescence: grade and gender comparisons. AB - The experience of being "in love" was studied in a sample of 186 early to middle adolescent males and 199 early to middle adolescent females. Results indicated that amount of dating experience of adolescents varied widely at each age. Being "in love" co-occurred with a reciprocal on-going relationship about half the time. Boys fell in love earlier and more often than girls, and both genders seemed to employ an increasingly narrow prototypical conception of being "in love". Qualitative analyses suggested that early and middle adolescents are actively reasoning about the nature and meaning of romantic feelings and experiences. Results are interpreted from the standpoint of psychosocial developmental theory, and implications for interventions with adolescents are discussed. PMID- 9971726 TI - Significant individuals in adolescence: adolescent and adult perspectives. AB - This study examines the ways in which 360 Israeli adolescents, and 395 midlife adults looking retrospectively perceive significant individuals from their adolescence. Following the methodology developed by Hendry et al. (Journal of Adolescence 1992, 15, 255-270), participants were asked to chose the most significant family and non-family individuals in their adolescent lives, and to indicate which of a number of characteristics applied or did not apply to their chosen significant persons. Our results indicate that most of the adults and the adolescents chose a parent as the most significant relative in their adolescence and that females in both samples chose their mothers more than did males. Compared with adolescents, adults attributed, retrospectively, more negative characteristics to their parents (e.g. as being mollycoddlers and rejectors). Adults were more likely to mention their teachers as significant non-family individuals in their lives and to characterize them in terms of their future impact as teachers and role models. Adolescents referred more positively to their parents, they also chose more friends of the same or opposite sex as significant others, and characterized them in terms of present-oriented features as being supporters and challengers. PMID- 9971728 TI - First sexual intercourse: anticipation and communication. Interviews with young people in England. AB - This study investigated anticipation and communication around first sexual intercourse through semi-structured interviews with young people (aged 16 to 29) in England. Ranging from surprise to pre-planning, several different levels of anticipation are explored. The main findings are as follows: communication plays a central role, mediating between the degree of anticipation and the degree to which first intercourse is wanted, protected and enjoyed. First intercourse tends to be characterized by silence, especially during early, spontaneous encounters. Silence does not imply lack of communication-non-verbal communication plays an important role. Where young people are ambivalent, verbal and non-verbal communication may send contradictory messages. The implications of the results for future safer sex campaigns are discussed. PMID- 9971727 TI - Social support and personal models of diabetesin relation to self-care and well being inadolescents with type I diabetes mellitus. AB - This study set out to examine whether peer support and illness representation mediates the link between family support, self-management and well-being. Seventy four participants (12-18-years-old) with type I diabetes mellitus completed questionnaires assessing their self-management, depression, anxiety, perceived social support and personal models of diabetes. Perceived impact of diabetes, but not perceived seriousness, and peer support were significant predictors of depression. Family support was a significant predictor of all self-management measures. However, for dietary self-management this relationship was partially mediated by the perceived efficacy of treatment to control diabetes, but not efficacy of treatment to prevent complications. PMID- 9971729 TI - Mum's the word: mothers' perspectives on communication about sexuality with adolescents. AB - Mothers' perceptions of the style, content and frequency of their communications with their adolescents about sex and sexuality were examined. We administered semi-structured interviews to 30 mothers of 16-year-olds (16 mothers of sons, 14 mothers of daughters). Despite a uniform assessment that they were effective sexual communicators, mothers varied greatly in their style of sexual communication. Qualitative analyses revealed five communication styles: avoidant, reactive, opportunistic, child-initiated and mutually interactive. These styles differed in who initiated and maintained sexual communication, the comfort level of mother and of teenager, the frequency of sexual communications, the context in which communications took place and the topics discussed and avoided. PMID- 9971730 TI - Young people in transition: the relationship between homesickness and self disclosure. AB - Whilst the majority of new students cope well with the transition to university, a number experience levels of homesickness which can adversely affect the process of adaptation. In this study the relationship between homesickness and self disclosure, seen as a possible mediating factor, was assessed in a sample of 83 students (mean age 18.0541 years, s.d.=7.055 months) at the start of their first semester and then 6 weeks later. The results showed that homesickness declined during the semester whilst levels of self-disclosure increased. A significant negative association was found between levels of self-disclosure and homesickness at both time periods. High self-disclosers experienced a significantly greater reduction in homesickness than low self-disclosers. The results showed the importance of the socially-mediated and supportive benefits of self-disclosure during this life transition. PMID- 9971733 TI - Volume contents and index PMID- 9971732 TI - Corrigendum PMID- 9971734 TI - Intraflagellar transport: the eyes have it. PMID- 9971735 TI - A novel in vivo assay reveals inhibition of ribosomal nuclear export in ran-cycle and nucleoporin mutants. AB - To identify components involved in the nuclear export of ribosomes in yeast, we developed an in vivo assay exploiting a green fluorescent protein (GFP)-tagged version of ribosomal protein L25. After its import into the nucleolus, L25-GFP assembles with 60S ribosomal subunits that are subsequently exported into the cytoplasm. In wild-type cells, GFP-labeled ribosomes are only detected by fluorescence in the cytoplasm. However, thermosensitive rna1-1 (Ran-GAP), prp20-1 (Ran-GEF), and nucleoporin nup49 and nsp1 mutants are impaired in ribosomal export as revealed by nuclear accumulation of L25-GFP. Furthermore, overexpression of dominant-negative RanGTP (Gsp1-G21V) and the tRNA exportin Los1p inhibits ribosomal export. The pattern of subnuclear accumulation of L25 GFP observed in different mutants is not identical, suggesting that transport can be blocked at different steps. Thus, nuclear export of ribosomes requires the nuclear/cytoplasmic Ran-cycle and distinct nucleoporins. This assay can be used to identify soluble transport factors required for nuclear exit of ribosomes. PMID- 9971736 TI - Mammalian homologue of the Caenorhabditis elegans UNC-76 protein involved in axonal outgrowth is a protein kinase C zeta-interacting protein. AB - By the yeast two-hybrid screening of a rat brain cDNA library with the regulatory domain of protein kinase C zeta (PKCzeta) as a bait, we have cloned a gene coding for a novel PKCzeta-interacting protein homologous to the Caenorhabditis elegans UNC-76 protein involved in axonal outgrowth and fasciculation. The protein designated FEZ1 (fasciculation and elongation protein zeta-1) consisting of 393 amino acid residues shows a high Asp/Glu content and contains several regions predicted to form amphipathic helices. Northern blot analysis has revealed that FEZ1 mRNA is abundantly expressed in adult rat brain and throughout the developmental stages of mouse embryo. By the yeast two-hybrid assay with various deletion mutants of PKC, FEZ1 was shown to interact with the NH2-terminal variable region (V1) of PKCzeta and weakly with that of PKCepsilon. In the COS-7 cells coexpressing FEZ1 and PKCzeta, FEZ1 was present mainly in the plasma membrane, associating with PKCzeta and being phosphorylated. These results indicate that FEZ1 is a novel substrate of PKCzeta. When the constitutively active mutant of PKCzeta was used, FEZ1 was found in the cytoplasm of COS-7 cells. Upon treatment of the cells with a PKC inhibitor, staurosporin, FEZ1 was translocated from the cytoplasm to the plasma membrane, suggesting that the cytoplasmic translocation of FEZ1 is directly regulated by the PKCzeta activity. Although expression of FEZ1 alone had no effect on PC12 cells, coexpression of FEZ1 and constitutively active PKCzeta stimulated the neuronal differentiation of PC12 cells. Combined with the recent finding that a human FEZ1 protein is able to complement the function of UNC-76 necessary for normal axonal bundling and elongation within axon bundles in the nematode, these results suggest that FEZ1 plays a crucial role in the axon guidance machinery in mammals by interacting with PKCzeta. PMID- 9971737 TI - Evidence that atypical protein kinase C-lambda and atypical protein kinase C-zeta participate in Ras-mediated reorganization of the F-actin cytoskeleton. AB - Expression of transforming Ha-Ras L61 in NIH3T3 cells causes profound morphological alterations which include a disassembly of actin stress fibers. The Ras-induced dissolution of actin stress fibers is blocked by the specific PKC inhibitor GF109203X at concentrations which inhibit the activity of the atypical aPKC isotypes lambda and zeta, whereas lower concentrations of the inhibitor which block conventional and novel PKC isotypes are ineffective. Coexpression of transforming Ha-Ras L61 with kinase-defective, dominant-negative (DN) mutants of aPKC-lambda and aPKC-zeta, as well as antisense constructs encoding RNA-directed against isotype-specific 5' sequences of the corresponding mRNA, abrogates the Ha Ras-induced reorganization of the actin cytoskeleton. Expression of a kinase defective, DN mutant of cPKC-alpha was unable to counteract Ras with regard to the dissolution of actin stress fibers. Transfection of cells with constructs encoding constitutively active (CA) mutants of atypical aPKC-lambda and aPKC-zeta lead to a disassembly of stress fibers independent of oncogenic Ha-Ras. Coexpression of (DN) Rac-1 N17 and addition of the phosphatidylinositol 3'-kinase (PI3K) inhibitors wortmannin and LY294002 are in agreement with a tentative model suggesting that, in the signaling pathway from Ha-Ras to the cytoskeleton aPKC lambda acts upstream of PI3K and Rac-1, whereas aPKC-zeta functions downstream of PI3K and Rac-1. This model is supported by studies demonstrating that cotransfection with plasmids encoding L61Ras and either aPKC-lambda or aPKC-zeta results in a stimulation of the kinase activity of both enzymes. Furthermore, the Ras-mediated activation of PKC-zeta was abrogated by coexpression of DN Rac-1 N17. PMID- 9971738 TI - Arginase II downregulates nitric oxide (NO) production and prevents NO-mediated apoptosis in murine macrophage-derived RAW 264.7 cells. AB - Excess nitric oxide (NO) induces apoptosis of some cell types, including macrophages. As NO is synthesized by NO synthase (NOS) from arginine, a common substrate of arginase, these two enzymes compete for arginine. There are two known isoforms of arginase, types I and II. Using murine macrophage-like RAW 264.7 cells, we asked if the induction of arginase II would downregulate NO production and hence prevent apoptosis. When cells were exposed to lipopolysaccharide (LPS) and interferon-gamma (IFN-gamma), the inducible form of NOS (iNOS) was induced, production of NO was elevated, and apoptosis followed. When dexamethasone and cAMP were further added, both iNOS and arginase II were induced, NO production was much decreased, and apoptosis was prevented. When the cells were transfected with an arginase II expression plasmid and treated with LPS/IFN-gamma, some cells were rescued from apoptosis. An arginase I expression plasmid was also effective. On the other hand, transfection with the arginase II plasmid did not prevent apoptosis when a NO donor SNAP or a high concentration (12 mM) of arginine was added. These results indicate that arginase II prevents NO-dependent apoptosis of RAW 264.7 cells by depleting intracellular arginine and by decreasing NO production. PMID- 9971739 TI - The intermediate filament protein peripherin is the specific interaction partner of mouse BPAG1-n (dystonin) in neurons. AB - The dystonia musculorum (dt) mouse suffers from severe degeneration of primary sensory neurons. The mutated gene product is named dystonin and is identical to the neuronal isoform of bullous pemphigoid antigen 1 (BPAG1-n). BPAG1-n contains an actin-binding domain at its NH2 terminus and a putative intermediate filament binding domain at its COOH terminus. Because the degenerating sensory neurons of dt mice display abnormal accumulations of intermediate filaments in the axons, BPAG1-n has been postulated to organize the neuronal cytoskeleton by interacting with both the neurofilament triplet proteins (NFTPs) and microfilaments. In this paper we show by a variety of methods that the COOH-terminal tail domain of mouse BPAG1 interacts specifically with peripherin, but in contrast to a previous study (Yang, Y., J. Dowling, Q.C. Yu, P. Kouklis, D.W. Cleveland, and E. Fuchs. 1996. Cell. 86:655-665), mouse BPAG1 fails to associate with full-length NFTPs. The tail domains interfered with the association of the NFTPs with BPAG1. In dt mice, peripherin is present in axonal swellings of degenerating sensory neurons in the dorsal root ganglia and is downregulated even in other neural regions, which have no obvious signs of pathology. Since peripherin and BPAG1-n also display similar expression patterns in the nervous system, we suggest that peripherin is the specific interaction partner of BPAG1-n in vivo. PMID- 9971740 TI - Slow axonal transport of neurofilament protein in cultured neurons. AB - We have investigated the axonal transport of neurofilament protein in cultured neurons by constricting single axons with fine glass fibers. We observed a rapid accumulation of anterogradely and retrogradely transported membranous organelles on both sides of the constrictions and a more gradual accumulation of neurofilament protein proximal to the constrictions. Neurofilament protein accumulation was dependent on the presence of metabolic substrates and was blocked by iodoacetate, which is an inhibitor of glycolysis. These data indicate that neurofilament protein moves anterogradely in these axons by a mechanism that is directly or indirectly dependent on nucleoside triphosphates. The average transport rate was estimated to be at least 130 micrometer/h (3.1 mm/d), and approximately 90% of the accumulated neurofilament protein remained in the axon after detergent extraction, suggesting that it was present in a polymerized form. Electron microscopy demonstrated that there were an abnormally large number of neurofilament polymers proximal to the constrictions. These data suggest that the neurofilament proteins were transported either as assembled polymers or in a nonpolymeric form that assembled locally at the site of accumulation. This study represents the first demonstration of the axonal transport of neurofilament protein in cultured neurons. PMID- 9971741 TI - Induction of integral membrane PAM expression in AtT-20 cells alters the storage and trafficking of POMC and PC1. AB - Peptidylglycine alpha-amidating monooxygenase (PAM) is an essential enzyme that catalyzes the COOH-terminal amidation of many neuroendocrine peptides. The bifunctional PAM protein contains an NH2-terminal monooxygenase (PHM) domain followed by a lyase (PAL) domain and a transmembrane domain. The cytosolic tail of PAM interacts with proteins that can affect cytoskeletal organization. A reverse tetracycline-regulated inducible expression system was used to construct an AtT-20 corticotrope cell line capable of inducible PAM-1 expression. Upon induction, cells displayed a time- and dose-dependent increase in enzyme activity, PAM mRNA, and protein. Induction of increased PAM-1 expression produced graded changes in PAM-1 metabolism. Increased expression of PAM-1 also caused decreased immunofluorescent staining for ACTH, a product of proopiomelanocortin (POMC), and prohormone convertase 1 (PC1) in granules at the tips of processes. Expression of PAM-1 resulted in decreased ACTH and PHM secretion in response to secretagogue stimulation, and decreased cleavage of PC1, POMC, and PAM. Increased expression of a soluble form of PAM did not alter POMC and PC1 localization and metabolism. Using the inducible cell line model, we show that expression of integral membrane PAM alters the organization of the actin cytoskeleton. Altered cytoskeletal organization may then influence the trafficking and cleavage of lumenal proteins and eliminate the ability of AtT-20 cells to secrete ACTH in response to a secretagogue. PMID- 9971743 TI - Growing pollen tubes possess a constitutive alkaline band in the clear zone and a growth-dependent acidic tip. AB - Using both the proton selective vibrating electrode to probe the extracellular currents and ratiometric wide-field fluorescence microscopy with the indicator 2', 7'-bis-(2-carboxyethyl)-5-(and-6)-carboxyfluorescein (BCECF)-dextran to image the intracellular pH, we have examined the distribution and activity of protons (H+) associated with pollen tube growth. The intracellular images reveal that lily pollen tubes possess a constitutive alkaline band at the base of the clear zone and an acidic domain at the extreme apex. The extracellular observations, in close agreement, show a proton influx at the extreme apex of the pollen tube and an efflux in the region that corresponds to the position of the alkaline band. The ability to detect the intracellular pH gradient is strongly dependent on the concentration of exogenous buffers in the cytoplasm. Thus, even the indicator dye, if introduced at levels estimated to be of 1.0 microM or greater, will dissipate the gradient, possibly through shuttle buffering. The apical acidic domain correlates closely with the process of growth, and thus may play a direct role, possibly in facilitating vesicle movement and exocytosis. The alkaline band correlates with the position of the reverse fountain streaming at the base of the clear zone, and may participate in the regulation of actin filament formation through the modulation of pH-sensitive actin binding proteins. These studies not only demonstrate that proton gradients exist, but that they may be intimately associated with polarized pollen tube growth. PMID- 9971742 TI - The DHC1b (DHC2) isoform of cytoplasmic dynein is required for flagellar assembly. AB - Dyneins are microtubule-based molecular motors involved in many different types of cell movement. Most dynein heavy chains (DHCs) clearly group into cytoplasmic or axonemal isoforms. However, DHC1b has been enigmatic. To learn more about this isoform, we isolated Chlamydomonas cDNA clones encoding a portion of DHC1b, and used these clones to identify a Chlamydomonas cell line with a deletion mutation in DHC1b. The mutant grows normally and appears to have a normal Golgi apparatus, but has very short flagella. The deletion also results in a massive redistribution of raft subunits from a peri-basal body pool (Cole, D.G., D.R. Diener, A.L. Himelblau, P.L. Beech, J.C. Fuster, and J.L. Rosenbaum. 1998. J. Cell Biol. 141:993-1008) to the flagella. Rafts are particles that normally move up and down the flagella in a process known as intraflagellar transport (IFT) (Kozminski, K.G., K.A. Johnson, P. Forscher, and J.L. Rosenbaum. 1993. Proc. Natl. Acad. Sci. USA. 90:5519-5523), which is essential for assembly and maintenance of flagella. The redistribution of raft subunits apparently occurs due to a defect in the retrograde component of IFT, suggesting that DHC1b is the motor for retrograde IFT. Consistent with this, Western blots indicate that DHC1b is present in the flagellum, predominantly in the detergent- and ATP-soluble fractions. These results indicate that DHC1b is a cytoplasmic dynein essential for flagellar assembly, probably because it is the motor for retrograde IFT. PMID- 9971744 TI - Membrane expansion increases endocytosis rate during mitosis. AB - Mitosis in mammalian cells is accompanied by a dramatic inhibition of endocytosis. We have found that the addition of amphyphilic compounds to metaphase cells increases the endocytosis rate even to interphase levels. Detergents and solvents all increased endocytosis rate, and the extent of increase was in direct proportion to the concentration added. Although the compounds could produce a variety of different effects, we have found a strong correlation with a physical alteration in the membrane tension as measured by the laser tweezers. Plasma membrane tethers formed by latex beads pull back on the beads with a force that was related to the in-plane bilayer tension and membrane- cytoskeletal adhesion. We found that as cells enter mitosis, the membrane tension rises as the endocytosis rate decreases; and as cells exited mitosis, the endocytosis rate increased as the membrane tension decreased. The addition of amphyphilic compounds decreased membrane tension and increased the endocytosis rate. With the detergent, deoxycholate, the endocytosis rate was restored to interphase levels when the membrane tension was restored to interphase levels. Although biochemical factors are clearly involved in the alterations in mitosis, we suggest that endocytosis is blocked primarily by the increase in apparent plasma membrane tension. Higher tensions inhibit both the binding of the endocytic complex to the membrane and mechanical deformation of the membrane during invagination. We suggest that membrane tension is an important regulator of the endocytosis rate and alteration of tension is sufficient to modify endocytosis rates during mitosis. Further, we postulate that the rise in membrane tension causes cell rounding and the inhibition of motility, characteristic of mitosis. PMID- 9971745 TI - Neurotransmitter secretion along growing nerve processes: comparison with synaptic vesicle exocytosis. AB - In mature neurons, synaptic vesicles continuously recycle within the presynaptic nerve terminal. In developing axons which are free of contact with a postsynaptic target, constitutive membrane recycling is not localized to the nerve terminal; instead, plasma membrane components undergo cycles of exoendocytosis throughout the whole axonal surface (Matteoli et al., 1992; Kraszewski et al., 1995). Moreover, in growing Xenopus spinal cord neurons in culture, acetylcholine (ACh) is spontaneously secreted in the quantal fashion along the axonal shaft (Evers et al., 1989; Antonov et al., 1998). Here we demonstrate that in Xenopus neurons ACh secretion is mediated by vesicles which recycle locally within the axon. Similar to neurotransmitter release at the presynaptic nerve terminal, ACh secretion along the axon could be elicited by the action potential or by hypertonic solutions. We found that the parameters of neurotransmitter secretion at the nerve terminal and at the middle axon were strikingly similar. These results lead us to conclude that, as in the case of the presynaptic nerve terminal, synaptic vesicles involved in neurotransmitter release along the axon contain a complement of proteins for vesicle docking and Ca2+-dependent fusion. Taken together, our results support the idea that, in developing axons, the rudimentary machinery for quantal neurotransmitter secretion is distributed throughout the whole axonal surface. Maturation of this machinery in the process of synaptic development would improve the fidelity of synaptic transmission during high-frequency stimulation of the presynaptic cell. PMID- 9971746 TI - delta-catenin, an adhesive junction-associated protein which promotes cell scattering. AB - The classical adherens junction that holds epithelial cells together consists of a protein complex in which members of the cadherin family linked to various catenins are the principal components. delta-catenin is a mammalian brain protein in the Armadillo repeat superfamily with sequence similarity to the adherens junction protein p120(ctn). We found that delta-catenin can be immunoprecipitated as a complex with other components of the adherens junction, including cadherin and beta-catenin, from transfected cells and brain. The interaction with cadherin involves direct contact within the highly conserved juxtamembrane region of the COOH terminus, where p120(ctn) also binds. In developing mouse brain, staining with delta-catenin antibodies is prominent towards the apical boundary of the neuroepithelial cells in the ventricular zone. When transfected into Madin-Darby canine kidney (MDCK) epithelial cells delta-catenin colocalized with cadherin, p120(ctn), and beta-catenin. The Arm domain alone was sufficient for achieving localization and coimmunoprecipitation with cadherin. The ectopic expression of delta-catenin in MDCK cells altered their morphology, induced the elaboration of lamellipodia, interfered with monolayer formation, and increased scattering in response to hepatocyte growth factor treatment. We propose that delta-catenin can regulate adhesion molecules to implement the organization of large cellular arrays necessary for tissue morphogenesis. PMID- 9971747 TI - DE-Cadherin is required for intercellular motility during Drosophila oogenesis. AB - Cadherins are involved in a variety of morphogenetic movements during animal development. However, it has been difficult to pinpoint the precise function of cadherins in morphogenetic processes due to the multifunctional nature of cadherin requirement. The data presented here indicate that homophilic adhesion promoted by Drosophila E-cadherin (DE-cadherin) mediates two cell migration events during Drosophila oogenesis. In Drosophila follicles, two groups of follicle cells, the border cells and the centripetal cells migrate on the surface of germline cells. We show that the border cells migrate as an epithelial patch in which two centrally located cells retain epithelial polarity and peripheral cells are partially depolarized. Both follicle cells and germline cells express DE-cadherin, and border cells and centripetal cells strongly upregulate the expression of DE-cadherin shortly before and during their migration. Removing DE cadherin from either the follicle cells or the germline cells blocks migration of border cells and centripetal cells on the surface of germline cells. The function of DE-cadherin in border cells appears to be specific for migration as the formation of the border cell cluster and the adhesion between border cells are not disrupted in the absence of DE-cadherin. The speed of migration depends on the level of DE-cadherin expression, as border cells migrate more slowly when DE cadherin activity is reduced. Finally, we show that the upregulation of DE cadherin expression in border cells depends on the activity of the Drosophila C/EBP transcription factor that is essential for border cell migration. PMID- 9971748 TI - Evidence that distinct states of the integrin alpha6beta1 interact with laminin and an ADAM. AB - Integrins can exist in different functional states with low or high binding capacity for particular ligands. We previously provided evidence that the integrin alpha6beta1, on mouse eggs and on alpha6-transfected cells, interacted with the disintegrin domain of the sperm surface protein ADAM 2 (fertilin beta). In the present study we tested the hypothesis that different states of alpha6beta1 interact with fertilin and laminin, an extracellular matrix ligand for alpha6beta1. Using alpha6-transfected cells we found that treatments (e.g., with phorbol myristate acetate or MnCl2) that increased adhesion to laminin inhibited sperm binding. Conversely, treatments that inhibited laminin adhesion increased sperm binding. Next, we compared the ability of fluorescent beads coated with either fertilin beta or with the laminin E8 fragment to bind to eggs. In Ca2+-containing media, fertilin beta beads bound to eggs via an interaction mediated by the disintegrin loop of fertilin beta and by the alpha6 integrin subunit. In Ca2+-containing media, laminin E8 beads did not bind to eggs. Treatment of eggs with phorbol myristate acetate or with the actin disrupting agent, latrunculin A, inhibited fertilin bead binding, but did not induce laminin E8 bead binding. Treatment of eggs with Mn2+ dramatically increased laminin E8 bead binding, and inhibited fertilin bead binding. Our results provide the first evidence that different states of an integrin (alpha6beta1) can interact with an extracellular matrix ligand (laminin) or a membrane-anchored cell surface ligand (ADAM 2). PMID- 9971749 TI - Laminin 5 in the human thymus: control of T cell proliferation via alpha6beta4 integrins. AB - Laminin 5 (alpha3beta3gamma2) distribution in the human thymus was investigated by immunofluorescence on frozen sections with anti-alpha3, -beta3, and -gamma2 mAbs. In addition to a linear staining of subcapsular basal laminae, the three mAbs give a disperse staining in the parenchyma restricted to the medullary area on a subset of stellate epithelial cells and vessel structures. We also found that laminin 5 may influence mature human thymocyte expansion; while bulk laminin and laminin 2, when cross-linked, are comitogenic with a TCR signal, cross-linked laminin 5 has no effect. By contrast, soluble laminin 5 inhibits thymocyte proliferation induced by a TCR signal. This is accompanied by a particular pattern of inhibition of early tyrosine kinases, including Zap 70 and p59(fyn) inhibition, but not overall inhibition of p56(lck). Using a mAb specific for alpha6beta4 integrins, we observed that while alpha3beta1 are known to be uniformly present on all thymocytes, alpha6beta4 expression parallels thymocyte maturation; thus a correspondence exists between laminin 5 in the thymic medulla and alpha6beta4 on mature thymocytes. Moreover, the soluble Ab against alpha6beta4 inhibits thymocyte proliferation and reproduces the same pattern of tyrosine kinase phosphorylation suggesting that alpha6beta4 is involved in laminin 5-induced modulation of T cell activation. PMID- 9971750 TI - Cell surface heparan sulfate proteoglycan syndecan-2 induces the maturation of dendritic spines in rat hippocampal neurons. AB - Dendritic spines are small protrusions that receive synapses, and changes in spine morphology are thought to be the structural basis for learning and memory. We demonstrate that the cell surface heparan sulfate proteoglycan syndecan-2 plays a critical role in spine development. Syndecan-2 is concentrated at the synapses, specifically on the dendritic spines of cultured hippocampal neurons, and its accumulation occurs concomitant with the morphological maturation of spines from long thin protrusions to stubby and headed shapes. Early introduction of syndecan-2 cDNA into immature hippocampal neurons, by transient transfection, accelerates spine formation from dendritic protrusions. Deletion of the COOH terminal EFYA motif of syndecan-2, the binding site for PDZ domain proteins, abrogates the spine-promoting activity of syndecan-2. Syndecan-2 clustering on dendritic protrusions does not require the PDZ domain-binding motif, but another portion of the cytoplasmic domain which includes a protein kinase C phosphorylation site. Our results indicate that syndecan-2 plays a direct role in the development of postsynaptic specialization through its interactions with PDZ domain proteins. PMID- 9971751 TI - Foamy viruses are unconventional retroviruses. PMID- 9971752 TI - Protection from lethal coxsackievirus-induced pancreatitis by expression of gamma interferon. AB - Coxsackievirus infection causes severe pancreatitis and myocarditis in humans, often leading to death in young or immunocompromised individuals. In susceptible strains of mice, coxsackievirus strain CB4 causes lethal hypoglycemia. To investigate the potential of gamma interferon (IFN-gamma) in protection and clearance of the viral infection, IFN-gamma knockout mice and transgenic (Tg) mice specifically expressing IFN-gamma in their pancreatic beta cells were infected with CB4. Lack of IFN-gamma in mice normally resistant to CB4-mediated disease resulted in hypoglycemia and rapid death. However, expression of IFN gamma in the beta cells of Tg mice otherwise susceptible to lethal infection allowed for survival and protected them from developing the accompanying hypoglycemia. While all the mice had high levels of viral replication in their pancreata and comparable tissue pathology following viral infection, the Tg mice had significantly lower levels of virus at the peak of infection, significantly higher numbers of activated macrophages before and after infection, and less damage to their acinar tissue. Additionally, despite having increased levels of inducible nitric oxide synthetase (iNOS) expression, treatment of Tg mice with the iNOS inhibitor aminoguanidine did not alter the level of protection afforded by IFN-gamma expression. In conclusion, IFN-gamma protects from lethal coxsackievirus infection by activating macrophages in an iNOS-independent manner. PMID- 9971753 TI - Reactivation of herpes simplex virus type 1 in the mouse trigeminal ganglion: an in vivo study of virus antigen and cytokines. AB - Reactivation of herpes simplex virus type 1 (HSV-1) in the trigeminal ganglion (TG) was induced by UV irradiation of the corneas of latently infected mice. Immunocytochemistry was used to monitor the dynamics of cytokine (interleukin-2 [IL-2], IL-4, IL-6, IL-10, gamma interferon [IFN-gamma], and tumor necrosis factor alpha [TNF-alpha]) and viral antigen production in the TG and the adjacent central nervous system on days 1 to 4, 6, 7, and 10 after irradiation. UV irradiation induced increased expression of IL-6 and TNF-alpha from satellite cells in uninfected TG. In latently infected TG, prior to reactivation, all satellite cells were TNF-alpha+ and most were also IL-6(+). Reactivation, evidenced by HSV-1 antigens and/or infiltrating immune cells, occurred in 28 of 45 (62%) TG samples. Viral antigens were present in the TG in neurons, often disintegrating on days 2 to 6 after irradiation. Infected neurons were usually surrounded by satellite cells and the foci of immune cells producing TNF-alpha and/or IL-6. IL-4(+) cells were detected as early as day 3 and were more numerous by day 10 (a very few IL-2(+) and/or IFN-gamma+ cells were seen at this time). No IL-10 was detected at any time. Our observations indicate that UV irradiation of the cornea may modulate cytokine production by satellite cells. We confirm that neurons are the site of reactivation and that they probably do not survive this event. The predominance of TNF-alpha and IL-6 following reactivation parallels primary infection in the TG and suggests a role in viral clearance. The presence of Th2-type cytokines (IL-4 and IL-6) indicates a role for antibody. Thus, several clearance mechanisms may be at work. PMID- 9971754 TI - Severe leukopenia and dysregulated erythropoiesis in SCID mice persistently infected with the parvovirus minute virus of mice. AB - Parvovirus minute virus of mice strain i (MVMi) infects committed granulocyte macrophage CFU and erythroid burst-forming unit (CFU-GM and BFU-E, respectively) and pluripotent (CFU-S) mouse hematopoietic progenitors in vitro. To study the effects of MVMi infection on mouse hemopoiesis in the absence of a specific immune response, adult SCID mice were inoculated by the natural intranasal route of infection and monitored for hematopoietic and viral multiplication parameters. Infected animals developed a very severe viral-dose-dependent leukopenia by 30 days postinfection (d.p.i.) that led to death within 100 days, even though the number of circulating platelets and erythrocytes remained unaltered throughout the disease. In the bone marrow of every lethally inoculated mouse, a deep suppression of CFU-GM and BFU-E clonogenic progenitors occurring during the 20- to 35-d.p.i. interval corresponded with the maximal MVMi production, as determined by the accumulation of virus DNA replicative intermediates and the yield of infectious virus. Viral productive infection was limited to a small subset of primitive cells expressing the major replicative viral antigen (NS-1 protein), the numbers of which declined with the disease. However, the infection induced a sharp and lasting unbalance of the marrow hemopoiesis, denoted by a marked depletion of granulomacrophagic cells (GR-1(+) and MAC-1(+)) concomitant with a twofold absolute increase in erythroid cells (TER-119(+)). A stimulated definitive erythropoiesis in the infected mice was further evidenced by a 12-fold increase per femur of recognizable proerythroblasts, a quantitative apoptosis confined to uninfected TER-119(+) cells, as well as by a 4-fold elevation in the number of circulating reticulocytes. Therefore, MVMi targets and suppresses primitive hemopoietic progenitors leading to a very severe leukopenia, but compensatory mechanisms are mounted specifically by the erythroid lineage that maintain an effective erythropoiesis. The results show that infection of SCID mice with the parvovirus MVMi causes a novel dysregulation of murine hemopoiesis in vivo. PMID- 9971755 TI - pH-dependent changes in photoaffinity labeling patterns of the H1 influenza virus hemagglutinin by using an inhibitor of viral fusion. AB - The hemagglutinin (HA) protein undergoes a low-pH-induced conformational change in the acidic milieu of the endosome, resulting in fusion of viral and cellular membranes. A class of compounds that specifically interact with the HA protein of H1 and H2 subtype viruses and inhibit this conformational change was recently described (G. X. Luo et al., Virology 226:66-76, 1996, and J. Virol. 71:4062 4070, 1997). In this study, purified HA trimers (bromelain-cleaved HA [BHA]) are used to examine the properties and binding characteristics of these inhibitors. Compounds were able to inhibit the low-pH-induced change of isolated trimers, as detected by resistance to digestion with trypsin. Protection from digestion was extremely stable, as BHA-inhibitor complexes could be incubated for 24 h in low pH with almost no change in BHA structure. One inhibitor was prepared as a radiolabeled photoaffinity analog and used to probe for specific drug interactions with the HA protein. Analysis of BHA after photoaffinity analog binding and UV cross-linking revealed that the HA2 subunit of the HA was specifically radiolabeled. Cross-linking of the photoaffinity analog to BHA under neutral (native) pH conditions identified a stretch of amino acids within the alpha-helix of HA2 that interact with the inhibitor. Interestingly, cross-linking of the analog under acidic conditions identified a different region within the HA2 N terminus which interacts with the photoaffinity compound. These attachment sites help to delineate a potential binding pocket and suggest a model whereby the BHA is able to undergo a partial, reversible structural change in the presence of inhibitor compound. PMID- 9971756 TI - Immune response-mediated protection of adult but not neonatal mice from neuron restricted measles virus infection and central nervous system disease. AB - In many cases of neurological disease associated with viral infection, such as measles virus (MV)-induced subacute sclerosing panencephalitis in children, it is unclear whether the virus or the antiviral immune response within the brain is the cause of disease. MV inoculation of transgenic mice expressing the human MV receptor, CD46, exclusively in neurons resulted in neuronal infection and fatal encephalitis within 2 weeks in neonates, while mice older than 3 weeks of age were resistant to both infection and disease. At all ages, T lymphocytes infiltrated the brain in response to inoculation. To determine the role of lymphocytes in disease progression, CD46(+) mice were back-crossed to T- and B cell-deficient RAG-2 knockout mice. The lymphocyte deficiency did not affect the outcome of disease in neonates, but adult CD46(+) RAG-2(-) mice were much more susceptible to both neuronal infection and central nervous system disease than their immunocompetent littermates. These results indicate that CD46-dependent MV infection of neurons, rather than the antiviral immune response in the brain, produces neurological disease in this model system and that immunocompetent adult mice, but not immunologically compromised or immature mice, are protected from infection. PMID- 9971757 TI - The hypervariable domain of the murine leukemia virus surface protein tolerates large insertions and deletions, enabling development of a retroviral particle display system. AB - The surface proteins (SU) of murine type-C retroviruses have a central hypervariable domain devoid of cysteine and rich in proline. This 41-amino-acid region of Friend ecotropic murine leukemia virus SU was shown to be highly tolerant of insertions and deletions. Viruses in which either the N-terminal 30 amino acids or the C-terminal 22 amino acids of this region were replaced by the 7-amino-acid sequence ASAVAGA were fully infectious. Insertions of this 7-amino acid sequence at the N terminus, center, and the C terminus of the hypervariable domain had little effect on envelope protein (Env) function, while this insertion at a position 10 amino acids following the N terminus partially destabilized the association between the SU and transmembrane subunits of Env. Large, complex domains (either a 252-amino-acid single-chain antibody binding domain [scFv] or a 96-amino-acid V1/V2 domain of HIV-1 SU containing eight N-linked glycosylation sites and two disulfides) did not interfere with Env function when inserted in the center or C-terminal portions of the hypervariable domain. The scFv domain inserted into the C-terminal region of the hypervariable domain was shown to mediate binding of antigen to viral particles, demonstrating that it folded into the active conformation and was displayed on the surface of the virion. Both positive and negative enrichment of virions expressing the V1/V2 sequence were achieved by using a monoclonal antibody specific for a conformational epitope presented by the inserted sequence. These results indicated that the hypervariable domain of Friend ecotropic SU does not contain any specific sequence or structure that is essential for Env function and demonstrated that insertions into this domain can be used to extend particle display methodologies to complex protein domains that require expression in eukaryotic cells for glycosylation and proper folding. PMID- 9971758 TI - Functional interactions of the HHCC domain of moloney murine leukemia virus integrase revealed by nonoverlapping complementation and zinc-dependent dimerization. AB - The retroviral integrase (IN) is required for the integration of viral DNA into the host genome. The N terminus of IN contains an HHCC zinc finger-like motif, which is conserved among all retroviruses. To study the function of the HHCC domain of Moloney murine leukemia virus IN, the first N-terminal 105 residues were expressed independently. This HHCC domain protein is found to complement a completely nonoverlapping construct lacking the HHCC domain for strand transfer, 3' processing and coordinated disintegration reactions, revealing trans interactions among IN domains. The HHCC domain protein binds zinc at a 1:1 ratio and changes its conformation upon binding to zinc. The presence of zinc within the HHCC domain stimulates selective integration processes. Zinc promotes the dimerization of the HHCC domain and protects it from N-ethylmaleimide modification. These studies dissect and define the requirement for the HHCC domain, the exact function of which remains unknown. PMID- 9971759 TI - Genetic analysis of a unique human immunodeficiency virus type 1 (HIV-1) with a primer binding site complementary to tRNAMet supports a role for U5-PBS stem-loop RNA structures in initiation of HIV-1 reverse transcription. AB - Human immunodeficiency virus type 1 (HIV-1) exclusively uses tRNA3Lys to initiate reverse transcription. A novel HIV-1 mutant which stably utilizes tRNAMet rather than tRNA3Lys as a primer was previously identified [HXB2(Met-AC] (S.-M. Kang, Z. Zhang, and C. D. Morrow, J. Virol. 71:207-217, 1997). Comparison of RNA secondary structures of the unique sequence (U5)-primer binding site (PBS) viral RNA genome alone or complexed with tRNAMet of HXB2(Met-AC) revealed structural motifs in common with the U5-PBS of the wild-type virus. In the current study, mutations were constructed to alter the U5-PBS structure and disrupt the U5-PBS-tRNAMet interaction of the virus derived from HXB2(Met-AC). All of the mutant viruses were infectious following transfection and coculture with SupT1 cells. Analysis of the initiation of reverse transcription revealed that some of the mutants were impaired compared to HXB2(Met-AC). The genetic stability of the PBS from each virus was determined following in vitro culture. Two mutant proviral constructs, one predicted to completely disrupt the stem-loop structure in U5 and the other predicted to destabilize contact regions of U5 with tRNAMet, reverted back to contain a PBS complementary to tRNA3Lys. All other mutants maintained a PBS complementary to tRNAMet after in vitro culture, although all contained multiple nucleotide substitutions within the U5-PBS from the starting proviral clones. Most interestingly, a viral mutant containing a 32-nucleotide deletion between nucleotides 142 and 173, encompassing regions in U5 which interact with tRNAMet, maintained a PBS complementary to tRNAMet following in vitro culture. All of the proviral clones recovered from this mutant, however, contained an additional 19 nucleotide insertion in U5. RNA modeling of the U5-PBS from this mutant demonstrated that the additional mutations present in U5 following culture restored RNA structures similar to those modeled from HXB2(Met-AC). These results provide strong genetic evidence that multiple sequence and structural elements in U5 in addition to the PBS are involved in the interaction with the tRNA used for initiation of reverse transcription. PMID- 9971760 TI - Requirements for efficient production and transduction of human immunodeficiency virus type 1-based vectors. AB - A number of human immunodeficiency type 1 (HIV-1)-based vectors have recently been shown to transduce nondividing cells in vivo as well as in vitro. However, if these vectors are to be considered for eventual clinical use, a major consideration is to reduce the probability of unintended generation of replication-competent virus. This can be achieved by eliminating viral genetic elements involved in the generation of replication-competent virus without impairing vector production. We have designed a system to transiently produce HIV 1-based vectors by using expression plasmids encoding Gag, Pol, and Tat of HIV-1 under the control of the cytomegalovirus immediate-early promoter. Our data show that the best vector yield is achieved in the presence of the Rev/Rev-responsive element (RRE) system. However, the constitutive transport element of Mason-Pfizer monkey virus can substitute for RRE and Rev at least to some extent, whereas the posttranscriptional regulatory element of human hepatitis B virus appeared to be inefficient. In addition, we show that high-titer virus preparations can be obtained in the presence of sodium butyrate, which activates the expression of both the packaging construct and the vector genome. Finally, our results suggest that efficient infectivity of vectors defective in the accessory proteins Vif, Vpr, Vpu, and Nef depends on the nature of the target cells. PMID- 9971761 TI - DNA replication of human papillomavirus type 31 is modulated by elements of the upstream regulatory region that lie 5' of the minimal origin. AB - The viral replication factors E1 and E2 of papillomaviruses are necessary and sufficient to replicate plasmids containing the minimal origin of DNA replication in transient assays. Under physiological conditions, the upstream regulatory region (URR) governs expression of the early viral genes. To determine the effect of URR elements on E1 and E2 expression specifically, and on the regulation of DNA replication during the various phases of the viral life cycle, we carried out a systematic replication study with entire genomes of human papillomavirus type 31 (HPV31), a high-risk oncogenic type. We constructed a series of URR deletions, spacer replacements, and point mutations to analyze the role of the keratinocyte enhancer (KE) element, the auxiliary enhancer (AE) domain, and the L1-proximal end of the URR (5'-URR domain) in DNA replication during establishment, maintenance, and vegetative viral DNA amplification. Using transient and stable replication assays, we demonstrate that the KE and AE are necessary for efficient E1 and E2 gene expression and that the KE can also directly modulate viral replication. KE-mediated activation of replication is dependent on the position and orientation of the element. Mutation of either one of the four Ap1 sites, the single Sp1 site, or the binding site for the uncharacterized footprint factor 1 reduced replication efficiency through decreased expression of E1 and E2. Furthermore, the 5'-URR domain and the Oct1 DNA binding site are dispensable for viral replication, since such HPV31 mutants are able to replicate efficiently in a transient assay, maintain a stable copy number over several cell generations, and amplify viral DNA under vegetative conditions. Interestingly, deletion of the 5'-URR domain leads to increased transient and stable replication levels. These findings suggest that elements in the HPV31 URR outside the minimal origin modulate viral replication through both direct and indirect mechanisms. PMID- 9971762 TI - vig-1, a new fish gene induced by the rhabdovirus glycoprotein, has a virus induced homologue in humans and shares conserved motifs with the MoaA family. AB - We used mRNA differential display methodology to analyze the shift of transcription profile induced by the fish rhabdovirus, viral hemorrhagic septicemia virus (VHSV), in rainbow trout leukocytes. We identified and characterized a new gene which is directly induced by VHSV. This VHSV-induced gene (vig-1) encodes a 348-amino-acid protein. vig-1 is highly expressed during the experimental disease in lymphoid organs of the infected fish. Intramuscular injection of a plasmid vector expressing the viral glycoprotein results in vig-1 expression, showing that the external virus protein is sufficient for the induction. vig-1 expression is also obtained by a rainbow trout interferon-like factor, indicating that vig-1 can be induced through different pathways. Moreover, vig-1 is homologous to a recently described human cytomegalovirus induced gene. Accordingly, vig-1 activation may represent a new virus-induced activation pathway highly conserved in vertebrates. The deduced amino acid sequence of vig-1 is significantly related to sequences required for the biosynthesis of metal cofactors. This suggests that the function of vig-1 may be involved in the nonspecific virus-induced synthesis of enzymatic cofactors of the nitric oxide pathway. PMID- 9971763 TI - Acute effects of pathogenic simian-human immunodeficiency virus challenge on vaccine-induced cellular and humoral immune responses to Gag in rhesus macaques. AB - Simian-human immunodeficiency virus (SHIV) infection in macaques provides a convenient model for testing vaccine efficacy and for understanding viral pathogenesis in AIDS. We immunized macaques with recombinant, Salmonella typhimurium (expressing Gag) or soluble Gag in adjuvant to generate T-cell dependent lymphoproliferative or serum antibody responses. Immunized animals were challenged by intrarectal inoculation with SHIV89.6PD. Virus infection was accompanied by rapid losses of lymphoproliferative responses to Gag or phytohemagglutinin. By 8 weeks, mitogen responses recovered to near normal levels but antigen-specific immunity remained at low or undetectable levels. Serum antibody levels were elevated initially by virus exposure but soon dropped well below levels achieved by immunization. Our studies show a rapid depletion of preexisting Gag-specific CD4(+) T cells that prevent or limit subsequent antiviral cellular and humoral immune responses during acute SHIV infection. PMID- 9971764 TI - Multiple functions for the basic amino acids of the human T-cell leukemia virus type 1 matrix protein in viral transmission. AB - We studied the involvement of the human T-cell leukemia virus type 1 (HTLV-1) Gag matrix protein in the cell-to-cell transmission of the virus using missense mutations of the basic amino acids. These basic amino acids are clustered at the N terminus of the protein in other retroviruses and are responsible for targeting the Gag proteins to the plasma membrane. In the HTLV-bovine leukemia virus genus of retroviruses, the basic amino acids are distributed throughout the matrix protein sequence. The HTLV-1 matrix protein contains 11 such residues. A wild type phenotype was obtained only for mutant viruses with mutations at one of two positions in the matrix protein. The phenotypes of the other nine mutant viruses showed that the basic amino acids are involved at various steps of the replication cycle, including some after membrane targeting. Most of these nine mutations allowed normal synthesis, transport, and cleavage of the Gag precursor, but particle release was greatly affected for seven of them. In addition, four mutated proteins with correct particle release and envelope glycoprotein incorporation did not however permit cell-to-cell transmission of HTLV-1. Thus, particle release, although required, is not sufficient for the cell-to-cell transmission of HTLV-1, and the basic residues of the matrix protein are involved in steps that occur after viral particle release. PMID- 9971765 TI - Factors governing the activity in vivo of ribozymes transcribed by RNA polymerase III. AB - In order to determine the parameters that govern the activity of a ribozyme in vivo, we made a systematic analysis of chimeric tRNAVal ribozymes by measuring their cleavage activities in vitro as well as the steady-state levels of transcripts, the half-lives of transcribed tRNAVal ribozymes, and their activities in both HeLa and H9 cells. These analyses were conducted by the use of transient expression systems in HeLa cells and stable transformants that express ribozymes. Localization of transcripts appeared to be determined by the higher order structure of each transcribed tRNAVal ribozyme. Since colocalization of the ribozyme with its target RNA is important for strong activity of the ribozyme in vivo, the best system for tRNA-based expression seems to be one in which the structure of the transcript is different from that of the natural tRNA precursor so that processing of the tRNAVal ribozyme can be avoided. At the same time, the structure of the transcript must be similar enough to allow recognition, probably by an export receptor, so that the transcript can be exported to the cytoplasm to ensure colocalization with its target. In the case of several tRNAVal ribozymes that we constructed, inspection of computer-predicted secondary structures enabled us to control the export of transcripts. We found that only a ribozyme that was transcribed at a high level and that had a sufficiently long half-life, within cells, had significant activity when used to withstand a challenge by human immunodeficiency virus type 1. PMID- 9971766 TI - Independence of evolutionary and mutational rates after transmission of avian influenza viruses to swine. AB - In 1979, an H1N1 avian influenza virus crossed the species barrier, establishing a new lineage in European swine. Because there is no direct or serologic evidence of previous H1N1 strains in these pigs, these isolates provide a model for studying early evolution of influenza viruses. The evolutionary rates of both the coding and noncoding changes of the H1N1 swine strains are higher than those of human and classic swine influenza A viruses. In addition, early H1N1 swine isolates show a marked plaque heterogeneity that consistently appears after a few passages. The presence of a mutator mutation was postulated (C. Scholtissek, S. Ludwig, and W. M. Fitch, Arch. Virol. 131:237-250, 1993) to account for these observations and the successful establishment of an avian H1N1 strain in swine. To address this question, we calculated the mutation rates of A/Mallard/New York/6750/78 (H2N2) and A/Swine/Germany/2/81 (H1N1) by using the frequency of amantadine-resistant mutants. To account for the inherent variability of estimated mutation rates, we used a probabilistic model for the statistical analysis. The resulting estimated mutation rates of the two strains were not significantly different. Therefore, an increased mutation rate due to the presence of a mutator mutation is unlikely to have led to the successful introduction of avian H1N1 viruses in European swine. PMID- 9971767 TI - Mapping of the hepatitis B virus reverse transcriptase TP and RT domains by transcomplementation for nucleotide priming and by protein-protein interaction. AB - Hepadnavirus polymerases initiate reverse transcription in a protein-primed reaction. We previously described a complementation assay for analysis of the roles of the TP and RT domains of HBV reverse transcriptase (pol) in the priming reaction. Independently expressed TP and RT domains form a complex functional for in vitro priming reactions. To map the minimal functional TP and RT domains, we prepared baculoviruses expressing amino- and carboxyl-terminal deletions of both the TP and RT domains and analyzed the proteins for the ability to participate in transcomplementation for the priming reaction. The minimal TP domain spanned amino acids 20 to 175; however, very little activity was observed without a TP domain spanning amino acids 1 to 199. The minimal RT domain spanned amino acids 300 to 775; however, little activity was observed unless the carboxyl end of the RT domain extended to amino acid 800. Thus, most of the RNase H domain was required. In previous studies, we observed a TP inhibitory domain between amino acids 199 and 344. The current analysis narrowed this domain to residues 300 to 334, which is a portion of the minimal RT domain. In addition, the ability of TP and RT deletion mutants to form stable TP-RT complexes was examined in coimmunoprecipitation assays. The minimal TP and RT domains capable of protein protein interaction were considerably smaller than the domains required for functional interaction in the transcomplementation assays, and unlike priming activity, TP-RT interaction did not require the epsilon RNA stem-loop. These studies help to further define the complex protein-protein interactions required in HBV genome replication. PMID- 9971768 TI - Cell cycle arrest during measles virus infection: a G0-like block leads to suppression of retinoblastoma protein expression. AB - One of the major mechanisms by which measles virus (MV) infection causes disease and death is suppression of the immune response. The nonresponsiveness of MV infected human lymphocytes to mitogens and a partial block in the G0/G1 phase of the cell cycle observed in vitro is thought to reflect in vivo immunosuppression. In order to molecularly dissect MV-induced immunosuppression, we analyzed expression of surface activation markers and cell cycle-regulatory proteins in MV infected human T lymphocytes. MV Edmonston (MV-Ed) could induce and maintain a high level of the early activation marker CD69 in the absence of proliferation. Expression of cyclins D3 and E, which positively control entry into S phase, was also significantly decreased. Analysis of inhibitors of progression into S phase showed that a high level of p27 was maintained in the G0/G1-blocked subpopulation of MV-Ed-infected cells compared to the proliferating MV-infected cells. Furthermore, cell cycle-related upregulation of retinoblastoma (Rb) protein synthesis did not occur in the MV-Ed-infected lymphocytes. Acridine orange staining, which distinguishes cells in G0 from cells in G1, showed that RNA levels were not upregulated following activation, which is consistent with cells remaining in a G0 state. Although expression of surface activation markers indicated entry into the cycle, intracellular Rb and RNA levels suggested a quiescent state. These results indicate that MV can uncouple activation of T lymphocytes from transition of G0 to G1. PMID- 9971769 TI - Human immunodeficiency virus type 1 protease triggers a myristoyl switch that modulates membrane binding of Pr55(gag) and p17MA. AB - The human immunodeficiency virus type 1 (HIV-1) Pr55(gag) gene product directs the assembly of virions at the inner surface of the cell plasma membrane. The specificity of plasma membrane binding by Pr55(gag) is conferred by a combination of an N-terminal myristoyl moiety and a basic residue-rich domain. Although the myristate plus basic domain is also present in the p17MA proteolytic product formed upon Pr55(gag) maturation, the ability of p17MA to bind to membranes is significantly reduced. It was previously reported that the reduced membrane binding of p17MA was due to sequestration of the myristate moiety by a myristoyl switch (W. Zhou and M. D. Resh, J. Virol. 70:8540-8548, 1996). Here we demonstrate directly that treatment of membrane-bound Pr55(gag) in situ with HIV 1 protease generates p17MA, which is then released from the membrane. Pr55(gag) was synthesized in reticulocyte lysates, bound to membranes, and incubated with purified HIV-1 protease. The p17MA product in the membrane-bound and soluble fractions was analyzed following proteolysis. Newly generated p17MA initially was membrane bound but then displayed a slow, time-dependent dissociation resulting in 65% solubilization. Residual p17MA could be extracted from the membranes with either high pH or high salt. Treatment of membranes from transfected COS-1 cells with protease revealed that Pr55(gag) was present within sealed membrane vesicles and that the release of p17MA occurred only when detergent and salt were added. We present a model proposing that the HIV-1 protease is the "trigger" for a myristoyl switch mechanism that modulates the membrane associations of Pr55(gag) and p17MA in virions and membranes. PMID- 9971770 TI - Kaposi's sarcoma-associated herpesvirus encodes a bZIP protein with homology to BZLF1 of Epstein-Barr virus. AB - Kaposi's sarcoma-associated herpesvirus (KSHV) is a recently discovered human gamma herpesvirus strongly implicated in AIDS-related neoplasms. We report here the identification in the KSHV genome of a gene for a protein designated K-bZIP and belonging to the basic-leucine zipper (bZIP) family of transcription factors. K-bZIP shows significant homology to BZLF1, which plays a key role in the replication and reactivation of Epstein-Barr virus. K-bZIP is a homodimerizing protein of 237 amino acids with a prototypic bZIP domain at the C terminus. The N terminal portion of K-bZIP is derived from the K8 open reading frame which, through in-frame splicing, adjoins the ZIP domain. This structure was revealed by rapid analysis of cDNA ends, followed by cloning of the entire cDNA. A 1.35-kb transcript encoding K-bZIP was detected in BCBL-1 cells treated with 12-O tetradecanoylphorbol-13-acetate. The synthesis of this transcript was blocked by the protein synthesis inhibitor cycloheximide but not by the viral DNA synthesis inhibitor phosphonoacetate, a result which classifies it as an early lytic gene. RNase protection analysis further mapped the major transcription start site for the 1.35-kb K-bZIP mRNA and identified two other splice variants which encode proteins with the N-terminal portion of K-bZIP but lacking the C-terminal ZIP domain. Full-length K-bZIP forms dimers with itself, and the C terminus encompassing the ZIP domain is required for this process. Our studies set the stage for understanding the role of K-bZIP in the replication and reactivation of the KSHV genome. PMID- 9971771 TI - The chromatin structure of the long control region of human papillomavirus type 16 represses viral oncoprotein expression. AB - The long control region (LCR) of human papillomavirus type 16 (HPV-16) has a size of 850 bp (about 12% of the viral genome) and regulates transcription and replication of the viral DNA. The 5' segment of the LCR contains transcription termination signals and a nuclear matrix attachment region, the central segment contains an epithelial cell-specific enhancer, and the 3' segment contains the replication origin and the E6 promoter. Here we report observations on the chromatin organization of this part of the HPV-16 genome. Treatment of the nuclei of CaSki cells, a cell line with 500 intrachromosomal copies of HPV-16, with methidiumpropyl-EDTA-Fe(II) reveals nucleosomes in specific positions on the LCR and the E6 and E7 genes. One of these nucleosomes, which we termed Ne, overlaps with the center of the viral enhancer, while a second nucleosome, Np16, overlaps with the replication origin and the E6 promoter. The two nucleosomes become positioned on exactly the same segments after in vitro assembly of chromatin on the cloned HPV-16 LCR. Primer extension mapping of DNase I-cleaved chromatin revealed Np16 to be positioned centrally over E6 promoter elements, extending into the replication origin. Ne covers the center of the enhancer but leaves an AP-1 site, one of the strongest cis-responsive elements of the enhancer, unprotected. Np16, or a combination of Np16 and Ne, represses the activity of the E6 promoter during in vitro transcription of HPV-16 chromatin. Repression is relieved by addition of Sp1 and AP-1 transcription factors. Sp1 alters the structure of Np16 in vitro, while no changes can be observed during the binding of AP-1. HPV-18, which has a similar arrangement of cis-responsive elements despite its evolutionary divergence from HPV-16, shows specific assembly in vitro of a nucleosome, Np18, over the E1 binding site and E6 promoter elements but positioned about 90 bp 5' of the position of Np16 on the homologous HPV-16 sequences. The chromatin organization of the HPV-16 and HPV-18 genomes suggests important regulatory roles of nucleosomes during the viral life cycle. PMID- 9971772 TI - Actin associates with the nucleocapsid domain of the human immunodeficiency virus Gag polyprotein. AB - Recently, it was shown that actin molecules are present in human immunodeficiency virus type 1 (HIV-1) particles. We have examined the basis for incorporation and the location of actin molecules within HIV-1 and murine retrovirus particles. Our results show that the retroviral Gag polyprotein is sufficient for actin uptake. Immunolabeling studies demonstrate that actin molecules localize to a specific radial position within the immature particle, clearly displaced from the matrix domain underneath the viral membrane but in proximity to the nucleocapsid (NC) domain of the Gag polyprotein. When virus or subviral Gag particles were disrupted with nonionic detergent, actin molecules remained associated with the disrupted particles. Actin molecules remained in a stable complex with the NC cleavage product (or an NC-RNA complex) after treatment of the disrupted HIV-1 particles with recombinant HIV-1 protease. In contrast, matrix and capsid molecules were released. The same result was obtained when mature HIV-1 particles were disrupted with detergent. Taken together, these results indicate that actin molecules are associated with the NC domain of the viral polyprotein. PMID- 9971773 TI - Molecular evolution of the human enteroviruses: correlation of serotype with VP1 sequence and application to picornavirus classification. AB - Sixty-six human enterovirus serotypes have been identified by serum neutralization, but the molecular determinants of the serotypes are unknown. Since the picornavirus VP1 protein contains a number of neutralization domains, we hypothesized that the VP1 sequence should correspond with neutralization (serotype) and, hence, with phylogenetic lineage. To test this hypothesis and to analyze the phylogenetic relationships among the human enteroviruses, we determined the complete VP1 sequences of the prototype strains of 47 human enterovirus serotypes and 10 antigenic variants. Our sequences, together with those available from GenBank, comprise a database of complete VP1 sequences for all 66 human enterovirus serotypes plus additional strains of seven serotypes. Phylogenetic trees constructed from complete VP1 sequences produced the same four major clusters as published trees based on partial VP2 sequences; in contrast to the VP2 trees, however, in the VP1 trees strains of the same serotype were always monophyletic. In pairwise comparisons of complete VP1 sequences, enteroviruses of the same serotype were clearly distinguished from those of heterologous serotypes, and the limits of intraserotypic divergence appeared to be about 25% nucleotide sequence difference or 12% amino acid sequence difference. Pairwise comparisons suggested that coxsackie A11 and A15 viruses should be classified as strains of the same serotype, as should coxsackie A13 and A18 viruses. Pairwise identity scores also distinguished between enteroviruses of different clusters and enteroviruses from picornaviruses of different genera. The data suggest that VP1 sequence comparisons may be valuable in enterovirus typing and in picornavirus taxonomy by assisting in the genus assignment of unclassified picornaviruses. PMID- 9971774 TI - Structure of adeno-associated virus vector DNA following transduction of the skeletal muscle. AB - The skeletal muscle provides a very permissive physiological environment for adeno-associated virus (AAV) type 2-mediated gene transfer. We have studied the early steps leading to the establishment of permanent transgene expression, after injection of recombinant AAV (rAAV) particles in the quadriceps muscle of mice. The animals received an rAAV encoding a secreted protein, murine erythropoietin (mEpo), under the control of the human cytomegalovirus major immediate-early promoter and were sacrificed between 1 and 60 days after injection. The measurement of plasma Epo levels and of hematocrits indicated a progressive increase of transgene expression over the first 2 weeks, followed by a stabilization at maximal plateau values. The rAAV sequences were analyzed by Southern blotting following neutral or alkaline gel electrophoresis of total DNA from injected muscles. While a high number of rAAV sequences were detected during the first 5 days following the injection, only a few percent of these sequences was retained in the animals analyzed after 2 weeks, in which transgene expression was maximal. Double-stranded DNA molecules resulting from de novo second-strand synthesis were detected as early as day 1, indicating that this crucial step of AAV-mediated gene transfer is readily accomplished in the muscle. The templates driving stable gene expression at later time points are low in copy number and structured as high-molecular-weight concatemers or interlocked circles. The presence of the circular form of the rAAV genomes at early time points suggests that the molecular transformations involved in the formation of stable concatemers may involve a rolling-circle type of DNA replication. PMID- 9971775 TI - Human immunodeficiency virus type 1 Tat induces apoptosis and increases sensitivity to apoptotic signals by up-regulating FLICE/caspase-8. AB - Apoptosis contributes to the loss of CD4 cells during human immunodeficiency virus type 1 (HIV-1) infection. Although the product of the env gene, gp160/gp120, is known to play a role in cell death mediated by HIV-1, the role of other HIV-1 genes in the process is unclear. We found that HIV-1 lacking the env gene (HIVDeltaenv) still induced apoptosis in T-cell lines and primary CD4 T cells. The ability to induce apoptosis was attributable to Tat, a viral regulatory protein. Tat induction of apoptosis was separate from the transactivation function of Tat, required expression of the second exon of Tat, and was associated with the increased expression and activity of caspase-8 (casp 8), a signaling molecule in apoptotic pathways. Moreover, induction of apoptosis could be prevented by treating cells with an inhibitor of casp-8. In addition, we show that HIV-1Deltaenv infection and Tat expression increased the sensitivity of cells to Fas-mediated apoptosis, an apoptotic pathway that signals via casp-8. The up-regulation of casp-8 by HIV-1 Tat expression may contribute to the increased apoptosis and sensitivity to apoptotic signals observed in the cells of HIV-1-infected persons. PMID- 9971777 TI - Generation of neutralizing human monoclonal antibodies against parvovirus B19 proteins. AB - Infections caused by human parvovirus B19 are known to be controlled mainly by neutralizing antibodies. To analyze the immune reaction against parvovirus B19 proteins, four cell lines secreting human immunoglobulin G monoclonal antibodies (MAbs) were generated from two healthy donors and one human immunodeficiency virus type 1-seropositive individual with high serum titers against parvovirus. One MAb is specific for nonstructural protein NS1 (MAb 1424), two MAbs are specific for the unique region of minor capsid protein VP1 (MAbs 1418-1 and 1418 16), and one MAb is directed to major capsid protein VP2 (MAb 860-55D). Two MAbs, 1418-1 and 1418-16, which were generated from the same individual have identity in the cDNA sequences encoding the variable domains, with the exception of four base pairs resulting in only one amino acid change in the light chain. The NS1- and VP1-specific MAbs interact with linear epitopes, whereas the recognized epitope in VP2 is conformational. The MAbs specific for the structural proteins display strong virus-neutralizing activity. The VP1- and VP2-specific MAbs have the capacity to neutralize 50% of infectious parvovirus B19 in vitro at 0.08 and 0.73 microgram/ml, respectively, demonstrating the importance of such antibodies in the clearance of B19 viremia. The NS1-specific MAb mediated weak neutralizing activity and required 47.7 micrograms/ml for 50% neutralization. The human MAbs with potent neutralizing activity could be used for immunotherapy of chronically B19 virus-infected individuals and acutely infected pregnant women. Furthermore, the knowledge gained regarding epitopes which induce strongly neutralizing antibodies may be important for vaccine development. PMID- 9971776 TI - Nef-induced CD4 and major histocompatibility complex class I (MHC-I) down regulation are governed by distinct determinants: N-terminal alpha helix and proline repeat of Nef selectively regulate MHC-I trafficking. AB - The Nef protein of primate lentiviruses triggers the accelerated endocytosis of CD4 and of class I major histocompatibility complex (MHC-I), thereby down modulating the cell surface expression of these receptors. Nef acts as a connector between the CD4 cytoplasmic tail and intracellular sorting pathways both in the Golgi and at the plasma membrane, triggering the de novo formation of CD4-specific clathrin-coated pits (CCP). The downstream partners of Nef in this event are the adapter protein complex (AP) of CCP and possibly a subunit of the vacuolar ATPase. Whether Nef-induced MHC-I down-regulation stems from a similar mechanism is unknown. By comparing human immunodeficiency virus type 1 (HIV-1) Nef mutants for their ability to affect either CD4 or MHC-I expression, both in transient-transfection assays and in the context of HIV-1 infection, it was determined that Nef-induced CD4 and MHC-I down-regulation constitute genetically and functionally separate properties. Mutations affecting only CD4 regulation mapped to residues previously shown to mediate the binding of Nef to this receptor, such as W57 and L58, as well as to an AP-recruiting dileucine motif and to an acidic dipeptide in the C-terminal region of the protein. In contrast, mutation of residues in an alpha-helical region in the proximal portion of Nef and amino acid substitutions in a proline-based SH3 domain-binding motif selectively affected MHC-I down-modulation. Although both the N-terminal alpha helix and the proline-rich region of Nef have been implicated in recruiting Src family protein kinases, the inhibitor herbimycin A did not block MHC-I down regulation, suggesting that the latter process is not mediated through an activation of this family of tyrosine kinases. PMID- 9971778 TI - Mechanisms that regulate Epstein-Barr virus EBNA-1 gene transcription during restricted latency are conserved among lymphocryptoviruses of Old World primates. AB - Epstein-Barr virus (EBV), the only known human lymphocryptovirus (LCV), displays a remarkable degree of genetic and biologic identity to LCVs that infect Old World primates. Within their natural hosts, infection by these viruses recapitulates many key aspects of EBV infection, including the establishment of long-term latency within B lymphocytes, and is therefore a potentially valuable animal model of EBV infection. However, it is unclear whether these LCVs have adopted or maintained the same mechanisms used by EBV to express essential viral proteins, such as EBNA-1, in the face of cell-mediated repression of EBV gene expression that occurs upon establishment of the asymptomatic carrier state. To address this issue, we determined whether the endogenous LCVs of baboon (Cercopithecine herpesvirus 12) and rhesus macaque (Cercopithecine herpesvirus 15) have the functional equivalent of the EBV promoter Qp, which mediates exclusive expression of EBNA-1 during the restricted programs of EBV latency associated with the carrier state. Our results indicate that (i) both the baboon and rhesus macaque LCVs have a genomic locus that is highly homologous to the EBV Qp region, (ii) key cis-regulatory elements of Qp are conserved in these LCV genomes and compose promoters that are functionally indistinguishable from EBV Qp, and (iii) EBNA-1 transcripts identical in structure to EBV Qp-specific EBNA-1 mRNAs are present in nonhuman LCV-infected cells, demonstrating that these Qp homologs are indeed utilized as alternative EBNA-1 promoters. These observations indicate that the molecular mechanisms which regulate EBV gene expression during restricted latency have been conserved among the LCVs. The contribution of these mechanisms to viral persistence in vivo can now be experimentally tested in nonhuman primate models of LCV infection. PMID- 9971779 TI - Chromatin structure of the simian virus 40 late promoter: a deletional analysis. AB - The goal of this study was to determine the minimal sequence within the simian virus 40 (SV40) late promoter region, nucleotides (nt) 255 to 424, capable of phasing nucleosomes as measured by its ability to confer the greatest endonuclease sensitivity on adjacent DNA sequences. To identify the minimal sequence, a deletional analysis of the late region was performed by utilizing a SV40 recombinant reporter system. The reporter system consisted of a series of unique restriction sites introduced into SV40 at nt 2666. The unique restriction sites allowed the insertion of test sequences as well as measurement of conferred endonuclease sensitivity. The results of the deletional analysis demonstrated that constructs capable of conferring the greatest nuclease sensitivities consistently included nt 255 to 280. The activator protein 4 (AP-4) and GTIIC transcription factor binding sequences lie within this region and were analyzed individually. Their abilities to confer nuclease sensitivity upon the reporter nearly matched that of the entire late domain. These results suggest that transcription factors AP-4 and transcription-enhancing factor which binds the GTIIC sequence are able to confer significant levels of nuclease sensitivity and are likely involved in the formation of the SV40 nucleosome-free region. PMID- 9971780 TI - Regulated expression of a Sindbis virus replicon by herpesvirus promoters. AB - We describe the use of herpesvirus promoters to regulate the expression of a Sindbis virus replicon (SINrep/LacZ). We isolated cell lines that contain the cDNA of SINrep/LacZ under the control of a promoter from a herpesvirus early gene which requires regulatory proteins encoded by immediate-early genes for expression. Wild-type Sindbis virus and replicons derived from this virus cause death of most vertebrate cells, but the cells discussed here grew normally and expressed the replicon and beta-galactosidase only after infection with a herpesvirus. Vero cell lines in which the expression of SINrep/LacZ was regulated by the herpes simplex virus type 1 (HSV-1) infected-cell protein 8 promoter were generated. One Vero cell line (V3-45N) contained, in addition to the SINrep/LacZ cDNA, a Sindbis virus-defective helper cDNA which provides the structural proteins for packaging the replicon. Infection of V3-45N cells with HSV-1 resulted in the production of packaged SINrep/LacZ replicons. HSV-1 induction of the Sindbis virus replicon and packaging and spread of the replicon led to enhanced expression of the reporter gene, suggesting that this type of cell could be used to develop sensitive assays to detect herpesviruses. We also isolated a mink lung cell line that was transformed with SINrep/LacZ cDNA under the control of the promoter from the human cytomegalovirus (HCMV) early gene UL45. HCMV carries out an abortive infection in mink lung cells, but it was able to induce the SINrep/LacZ replicon. These results, and those obtained with an HSV-1 mutant, demonstrate that this type of signal amplification system could be valuable for detecting herpesviruses for which a permissive cell culture system is not available. PMID- 9971781 TI - ATP depletion blocks herpes simplex virus DNA packaging and capsid maturation. AB - During herpes simplex virus (HSV) assembly, immature procapsids must expel their internal scaffold proteins, transform their outer shell to form mature polyhedrons, and become packaged with the viral double-stranded (ds) DNA genome. A large number of virally encoded proteins are required for successful completion of these events, but their molecular roles are poorly understood. By analogy with the dsDNA bacteriophage we reasoned that HSV DNA packaging might be an ATP requiring process and tested this hypothesis by adding an ATP depletion cocktail to cells accumulating unpackaged procapsids due to the presence of a temperature sensitive lesion in the HSV maturational protease UL26. Following return to permissive temperature, HSV capsids were found to be unable to package DNA, suggesting that this process is indeed ATP dependent. Surprisingly, however, the display of epitopes indicative of capsid maturation was also inhibited. We conclude that either formation of these epitopes directly requires ATP or capsid maturation is normally arrested by a proofreading mechanism until DNA packaging has been successfully completed. PMID- 9971782 TI - Open reading frame 1a-encoded subunits of the arterivirus replicase induce endoplasmic reticulum-derived double-membrane vesicles which carry the viral replication complex. AB - The replicase of equine arteritis virus (EAV; family Arteriviridae, order Nidovirales) is expressed in the form of two polyproteins (the open reading frame 1a [ORF1a] and ORF1ab proteins). Three viral proteases cleave these precursors into 12 nonstructural proteins, which direct both genome replication and subgenomic mRNA transcription. Immunofluorescence assays showed that most EAV replicase subunits localize to membranes in the perinuclear region of the infected cell. Using replicase-specific antibodies and cryoimmunoelectron microscopy, unusual double-membrane vesicles (DMVs) were identified as the probable site of EAV RNA synthesis. These DMVs were previously observed in cells infected with different arteriviruses but were never implicated in viral RNA synthesis. Extensive electron microscopic analysis showed that they appear to be derived from paired endoplasmic reticulum membranes and that they are most likely formed by protrusion and detachment of vesicular structures with a double membrane. Interestingly, very similar membrane rearrangements were observed upon expression of ORF1a-encoded replicase subunits nsp2 to nsp7 from an alphavirus based expression vector. Apparently, the formation of a membrane-bound scaffold for the replication complex is a distinct step in the arterivirus life cycle, which is directed by the ORF1a protein and does not depend on other viral proteins and/or EAV-specific RNA synthesis. PMID- 9971783 TI - Proteolytic processing of the open reading frame 1b-encoded part of arterivirus replicase is mediated by nsp4 serine protease and Is essential for virus replication. AB - The open reading frame (ORF) 1b-encoded part of the equine arteritis virus (EAV) replicase is expressed by ribosomal frameshifting during genome translation, which results in the production of an ORF1ab fusion protein (345 kDa). Four ORF1b encoded processing products, nsp9 (p80), nsp10 (p50), nsp11 (p26), and nsp12 (p12), have previously been identified in EAV-infected cells (L. C. van Dinten, A. L. M. Wassenaar, A. E. Gorbalenya, W. J. M. Spaan, and E. J. Snijder, J. Virol. 70:6625-6633, 1996). In the present study, the generation of these four nonstructural proteins was shown to be mediated by the nsp4 serine protease, which is the main viral protease (E. J. Snijder, A. L. M. Wassenaar, L. C. van Dinten, W. J. M. Spaan, and A. E. Gorbalenya, J. Biol. Chem. 271:4864-4871, 1996). Mutagenesis of candidate cleavage sites revealed that Glu-2370/Ser, Gln 2837/Ser, and Glu-3056/Gly are the probable nsp9/10, nsp10/11, and nsp11/12 junctions, respectively. Mutations which abolished ORF1b protein processing were introduced into a recently developed infectious cDNA clone (L. C. van Dinten, J. A. den Boon, A. L. M. Wassenaar, W. J. M. Spaan, and E. J. Snijder, Proc. Natl. Acad. Sci. USA 94:991-997, 1997). An analysis of these mutants showed that the selective blockage of ORF1b processing affected different stages of EAV reproduction. In particular, the mutant with the nsp10/11 cleavage site mutation Gln-2837-->Pro displayed an unusual phenotype, since it was still capable of RNA synthesis but was incapable of producing infectious virus. PMID- 9971784 TI - Identification of protein instability determinants in the carboxy-terminal region of c-Myb removed as a result of retroviral integration in murine monocytic leukemias. AB - The c-myb oncogene has been a target of retroviral insertional mutagenesis in murine monocytic leukemias. One mechanism by which c-myb can be activated is through the integration of a retroviral provirus into the central portion of the locus, causing premature termination of c-myb transcription and translation. We had previously shown that a leukemia-specific c-Myb protein, truncated at the site of proviral integration by 248 amino acids, had approximately a fourfold increased half-life compared to the normal c-Myb protein, due to its ability to escape rapid degradation by the ubiquitin-26S proteasome pathway. Here we provide evidence for the existence of more than one instability determinant in the carboxy-terminal region of the wild-type protein, which appear to act independently of each other. The data were derived from examination of premature termination mutants and deletion mutants of the normal protein, as well as analysis of another carboxy-terminally truncated protein expressed in leukemia. Evidence is provided that one instability determinant is located in the terminal 87 amino acids of the protein and another is located in the vicinity of the internal region that has leucine zipper homology. In leukemias, different degrees of protein stability are attained following proviral integration depending upon how many determinants are removed. Interestingly, although PEST sequences (rich in proline, glutamine, serine, and threonine), often associated with degradation, are found in c-Myb, deletion of PEST-containing regions had no effect on protein turnover. This study provides further insight into how inappropriate expression of c-Myb may contribute to leukemogenesis. In addition, it will facilitate further studies aimed at characterizing the specific role of individual regions of the normal protein in targeting to the 26S proteasome. PMID- 9971785 TI - Conditions for copackaging rous sarcoma virus and murine leukemia virus Gag proteins during retroviral budding. AB - Rous sarcoma virus (RSV) and murine leukemia virus (MLV) are examples of distantly related retroviruses that normally do not encounter one another in nature. Their Gag proteins direct particle assembly at the plasma membrane but possess very little sequence similarity. As expected, coexpression of these two Gag proteins did not result in particles that contain both. However, when the N terminal membrane-binding domain of each molecule was replaced with that of the Src oncoprotein, which is also targeted to the cytoplasmic face of the plasma membrane, efficient copackaging was observed in genetic complementation and coimmunoprecipitation assays. We hypothesize that the RSV and MLV Gag proteins normally use distinct locations on the plasma membrane for particle assembly but otherwise have assembly domains that are sufficiently similar in function (but not sequence) to allow heterologous interactions when these proteins are redirected to a common membrane location. PMID- 9971786 TI - Infection process of the hepatitis B virus depends on the presence of a defined sequence in the pre-S1 domain. AB - During the life cycle of hepatitis B virus (HBV), the large envelope protein (L) plays a pivotal role. Indeed, this polypeptide is essential for viral assembly and probably for the infection process. By performing mutagenesis experiments, we have previously excluded a putative involvement of the pre-S2 domain of the L protein in viral infectivity. In the present study, we have evaluated the role of the pre-S1 region in HBV infection. For this purpose, 21 mutants of the L protein were created. The entire pre-S1 domain was covered by contiguous deletions of 5 amino acids. First, after transfection into HepG2 cells, the efficient expression of both glycosylated and unglycosylated L mutant proteins was verified. The secretion rate of envelope proteins was modified positively or negatively by deletions, indicating that the pre-S1 domain contains several regulating sequences able to influence the surface protein secretion. The ability of mutant proteins to support the production of virions was then studied. Only the four C terminal deletions, covering the 17 amino acids suspected to interact with the cytoplasmic nucleocapsids, inhibited virion release. Finally, the presence of the modified pre-S1 domain at the external side of all secreted virions was confirmed, and their infectivity was assayed on normal human hepatocytes in primary culture. Only a short sequence including amino acids 78 to 87 tolerates internal deletions without affecting viral infectivity. These results confirm the involvement of the L protein in the infection step and demonstrate that the sequence between amino acids 3 and 77 is involved in this process. PMID- 9971787 TI - An important role for major histocompatibility complex class I-restricted T cells, and a limited role for gamma interferon, in protection of mice against lethal herpes simplex virus infection. AB - Herpes simplex virus (HSV) inhibits major histocompatibility complex (MHC) class I expression in infected cells and does so much more efficiently in human cells than in murine cells. Given this difference, if MHC class I-restricted T cells do not play an important role in protection of mice from HSV, an important role for these cells in humans would be unlikely. However, the contribution of MHC class I restricted T cells to the control of HSV infection in mice remains unclear. Further, the mechanisms by which these cells may act to control infection, particularly in the nervous system, are not well understood, though a role for gamma interferon (IFN-gamma) has been proposed. To address the roles of MHC class I and of IFN-gamma, C57BL/6 mice deficient in MHC class I expression (beta2 microglobulin knockout [beta2KO] mice), in IFN-gamma expression (IFN-gammaKO mice), or in both (IFN-gammaKO/beta2KO mice) were infected with HSV by footpad inoculation. beta2KO mice were markedly compromised in their ability to control infection, as indicated by increased lethality and higher concentrations of virus in the feet and spinal ganglia. In contrast, IFN-gamma appeared to play at most a limited role in viral clearance. The results suggest that MHC class I-restricted T cells play an important role in protection of mice against neuroinvasive HSV infection and do so largely by mechanisms other than the production of IFN-gamma. PMID- 9971788 TI - High-level replication of human immunodeficiency virus in thymocytes requires NF kappaB activation through interaction with thymic epithelial cells. AB - We have previously demonstrated that interaction of infected thymocytes with autologous thymic epithelial cells (TEC) is a prerequisite for a high level of human immunodeficiency virus type 1 (HIV-1) replication in thymocytes (M. Rothe, L. Chene, M. Nugeyre, F. Barre-Sinoussi, and N. Israel, J. Virol. 72:5852-5861, 1998). We report here that this activation of HIV replication takes place at the transcriptional level through activation of the Rel/NF-kappaB transcription factors. We first demonstrate that an HIV-1 provirus (SF-2 strain) very effectively replicates in thymocytes cocultured with TEC whereas this provirus, with kappaB sites deleted, fails to replicate. We provide evidence that several NF-kappaB complexes are constitutively found in the nuclei of thymocytes either freshly isolated from the thymus or maintained in coculture with autologous or heterologous TEC. The prevalent complex is the heterodimer p50-p65. NF-kappaB activity is tightly correlated with the transcriptional activity of a long terminal repeat (LTR) of HIV-1 transfected in thymocytes. The cotransfection of this LTR with a mutated IkappaBalpha molecule formally demonstrates that LTR transactivation is regulated by members of the Rel/NF-kappaB family in thymocytes. We also showed that tumor necrosis factor (TNF) and to a lesser extent interleukin-1 (IL-1), secreted within the coculture, induce NF-kappaB activity and a correlative LTR transactivation. However IL-7, a crucial factor for thymopoiesis that is secreted mainly by TEC, is a necessary cofactor for NF kappaB activation elicited by TNF or IL-1. Together, these data indicate that NF kappaB activation, required for a high level of HIV replication in thymocytes, is regulated in a specific manner in the thymic microenvironment which provides the necessary cytokines: TNF, IL-1, and IL-7. PMID- 9971789 TI - The replicative capacities of large E1B-null group A and group C adenoviruses are independent of host cell p53 status. AB - Recent reports suggest that an early region 1B (E1B) 55, 000-molecular-weight polypeptide (55K)-null adenovirus type 5 (Ad5) mutant (dl1520) can replicate to the same extent as wild-type (wt) Ad5 in cells either deficient or mutated in p53, implicating p53 in limiting viral replication in vivo. In contrast, we show here that the replicative capacity of Ad5 dl1520 is wholly independent of host cell p53 status, as is the replicative capacity of comparable Ad12 E1B 54K-null adenoviruses (Ad12 dl620 and Ad12 hr703). Furthermore, we show that there is no requirement for complex formation between p53 and Ad5 E1B 55K or Ad12 E1B 54K for a productive infection, such that wt Ad5 and wt Ad12 will both replicate in cells which are null for p53. In addition, we find that these Ad5 and Ad12 mutant viruses induce S phase irrespective of the p53 status of the cell and that, therefore, S-phase induction does not correlate with the replicative capacity of the virus. Interestingly, the replicative capacities of the large E1B-null adenoviruses correlated positively with the ability to express E1B 19K and were related to the ability to repress premature adenovirus-induced apoptosis. Infection of primary human cells indicated that Ad5 dl1520, wt Ad5, and wt Ad12 replicated better in cycling normal human skin fibroblasts (HSFs) than in quiescent HSFs. Thus, the cell cycle status of the host cell, upon infection, also influences viral yield. PMID- 9971790 TI - Analysis of the effects of charge cluster mutations in adeno-associated virus Rep68 protein in vitro. AB - The Rep78 and Rep68 proteins of adeno-associated virus type 2 (AAV) are multifunctional proteins which are required for viral replication, regulation of AAV promoters, and preferential integration of the AAV genome into a region of human chromosome 19. These proteins bind the hairpin structures formed by the AAV inverted terminal repeat (ITR) origins of replication, make site- and strand specific endonuclease cuts within the AAV ITRs, and display nucleoside triphosphate-dependent helicase activities. Additionally, several mutant Rep proteins display negative dominance in helicase and/or endonuclease assays when they are mixed with wild-type Rep78 or Rep68, suggesting that multimerization may be required for the helicase and endonuclease functions. Using overlap extension PCR mutagenesis, we introduced mutations within clusters of charged residues throughout the Rep68 moiety of a maltose binding protein-Rep68 fusion protein (MBP-Rep68Delta) expressed in Escherichia coli cells. Several mutations disrupted the endonuclease and helicase activities; however, only one amino-terminal-charge cluster mutant protein (D40A-D42A-D44A) completely lost AAV hairpin DNA binding activity. Charge cluster mutations within two other regions abolished both endonuclease and helicase activities. One region contains a predicted alpha helical structure (amino acids 371 to 393), and the other contains a putative 3,4 heptad repeat (coiled-coil) structure (amino acids 441 to 483). The defects displayed by these mutant proteins correlated with a weaker association with wild type Rep68 protein, as measured in coimmunoprecipitation assays. These experiments suggest that these regions of the Rep molecule are involved in Rep oligomerization events critical for both helicase and endonuclease activities. PMID- 9971791 TI - DNA vaccine encoding hemagglutinin provides protective immunity against H5N1 influenza virus infection in mice. AB - In Hong Kong in 1997, a highly lethal H5N1 avian influenza virus was apparently transmitted directly from chickens to humans with no intermediate mammalian host and caused 18 confirmed infections and six deaths. Strategies must be developed to deal with this virus if it should reappear, and prospective vaccines must be developed to anticipate a future pandemic. We have determined that unadapted H5N1 viruses are pathogenic in mice, which provides a well-defined mammalian system for immunological studies of lethal avian influenza virus infection. We report that a DNA vaccine encoding hemagglutinin from the index human influenza isolate A/HK/156/97 provides immunity against H5N1 infection of mice. This immunity was induced against both the homologous A/HK/156/97 (H5N1) virus, which has no glycosylation site at residue 154, and chicken isolate A/Ck/HK/258/97 (H5N1), which does have a glycosylation site at residue 154. The mouse model system should allow rapid evaluation of the vaccine's protective efficacy in a mammalian host. In our previous study using an avian model, DNA encoding hemagglutinin conferred protection against challenge with antigenic variants that differed from the primary antigen by 11 to 13% in the HA1 region. However, in our current study we found that a DNA vaccine encoding the hemagglutinin from A/Ty/Ir/1/83 (H5N8), which differs from A/HK/156/97 (H5N1) by 12% in HA1, prevented death but not H5N1 infection in mice. Therefore, a DNA vaccine made with a heterologous H5 strain did not prevent infection by H5N1 avian influenza viruses in mice but was useful in preventing death. PMID- 9971793 TI - A hairpin loop at the 5' end of influenza A virus virion RNA is required for synthesis of poly(A)+ mRNA in vitro. AB - We present evidence, based on extensive mutagenesis, that a hairpin loop at the 5' end of influenza A virus virion RNA (vRNA) is required for the synthesis of polyadenylated mRNA from model vRNA templates in vitro. The hairpin loop, which we term the vRNA 5' hook, contains a stem of 2 bp formed by the second and third residues pairing with the ninth and eighth residues, respectively, and a 4 nucleotide loop composed of the intervening residues 4 to 7. Disruption of the base pairs of the vRNA 5' hook by introducing point mutations prevented polyadenylation, except in two mutants where a G-U base pair reformed. The polyadenylation activity of point mutants could be rescued by constructing double mutants with reformed base pairs in the stem of the vRNA 5' hook. These results suggest that base pairing rather than a particular nucleotide sequence was critical. We also show that mutation of the analogous region in the 3' arm of vRNA did not interfere with the synthesis of polyadenylated mRNA, suggesting that a hook structure in the 3' arm is not required for transcription of polyadenylated mRNA in vitro. PMID- 9971792 TI - The memory cytotoxic T-lymphocyte (CTL) response to human cytomegalovirus infection contains individual peptide-specific CTL clones that have undergone extensive expansion in vivo. AB - Human cytomegalovirus (HCMV)-specific CD8(+) cytotoxic T lymphocytes (CTL) appear to play an important role in the control of virus replication and in protection against HCMV-related disease. We have previously reported high frequencies of memory CTL precursors (CTLp) specific to the HCMV tegument protein pp65 in the peripheral blood of healthy virus carriers. In some individuals, the CTL response to this protein is focused on only a single epitope, whereas in other virus carriers CTL recognized multiple epitopes which we identified by using synthetic peptides. We have analyzed the clonal composition of the memory CTL response to four of these pp65 epitopes by sequencing the T-cell receptors (TCR) of multiple independently derived epitope-specific CTL clones, which were derived by formal single-cell cloning or from clonal CTL microcultures. In all cases, we have observed a high degree of clonal focusing: the majority of CTL clones specific to a defined pp65 peptide from any one virus carrier use only one or two different TCRs at the level of the nucleotide sequence. Among virus carriers who have the same major histocompatibility complex (MHC) class I allele, we observed that CTL from different donors that recognize the same peptide-MHC complex often used the same Vbeta segment, although other TCR gene segments and CDR3 length were not in general conserved. We have also examined the clonal composition of CTL specific to pp65 peptides in asymptomatic human immunodeficiency virus-infected individuals. We have observed a similarly focused peptide-specific CTL response. Thus, the large population of circulating HCMV peptide-specific memory CTLp in virus carriers in fact contains individual CTL clones that have undergone extensive clonal expansion in vivo. PMID- 9971794 TI - CD21-Dependent infection of an epithelial cell line, 293, by Epstein-Barr virus. AB - Epstein-Barr virus (EBV) is invariably present in undifferentiated nasopharyngeal carcinomas, is found sporadically in other carcinomas, and replicates in the differentiated layer of the tongue epithelium in lesions of oral hairy leukoplakia. However, it is not clear how frequently or by what mechanism EBV infects epithelial cells normally. Here, we report that a human epithelial cell line, 293, can be stably infected by EBV that has been genetically marked with a selectable gene. We show that 293 cells express a relatively low level of CD21, that binding of fluorescein-labeled EBV to 293 cells can be detected, and that both the binding of virus to cells and infection can be blocked with antibodies specific for CD21. Two proteins known to form complexes with CD21 on the surface of lymphoid cells, CD35 and CD19, could not be detected at the surface of 293 cells. All infected clones of 293 cells exhibited tight latency with a pattern of gene expression similar to that of type II latency, but productive EBV replication and release of infectious virus could be induced inefficiently by forced expression of the lytic transactivators, R and Z. Low levels of mRNA specific for the transforming membrane protein of EBV, LMP-1, as well as for LMP 2, were detected; however, LMP-1 protein was either undetectable or near the limit of detection at less than 5% of the level typical of EBV-transformed B cells. A slight increase in expression of the receptor for epidermal growth factor, which can be induced in epithelial cells by LMP-1, was detected at the cell surface with two EBV-infected 293 cell clones. These results show that low levels of surface CD21 can support infection of an epithelial cell line by EBV. The results also raise the possibility that in a normal infection of epithelial cells by EBV, the LMP-1 protein is not expressed at levels that are high enough to be oncogenic and that there might be differences in the cells of EBV associated epithelial cancers that have arisen to allow for elevated expression of LMP-1. PMID- 9971795 TI - Human immunodeficiency virus type 1 integrase protein promotes reverse transcription through specific interactions with the nucleoprotein reverse transcription complex. AB - The human immunodeficiency virus type 1 (HIV-1) integrase protein (IN) is essential for integration of the viral DNA into host cell chromosomes. Since IN is expressed and assembled into virions as part of the 160-kDa Gag-Pol precursor polyprotein and catalyzes integration of the provirus in infected cells as a mature 32-kDa protein, mutations in IN are pleiotropic and may affect virus replication at different stages of the virus life cycle in addition to integration. Several different phenotypes have been observed for IN mutant viruses, including defects in virion morphology, protein composition, reverse transcription, nuclear import, and integration. Because the effects of mutations in the IN domain of Gag-Pol can not always be distinguished from those of mutations in the mature IN protein, there remains a significant gap in our understanding of IN function in vivo. To directly analyze the function of the mature IN protein itself, in the context of a replicating virus but independently from that of Gag-Pol, we used an approach developed in our laboratory for incorporating proteins into HIV virions by their expression in trans as fusion partners of either Vpr or Vpx. By providing IN in trans as a Vpr-IN fusion protein, our analysis revealed, for the first time, that the mature IN protein is essential for the efficient initiation of reverse transcription in infected cells and that this function does not require the IN protein to be enzymatically (integration) active. Our findings of a direct physical interaction between IN and reverse transcriptase and the failure of heterologous HIV-2 IN protein to efficiently support reverse transcription indicate that this novel function occurs through specific interactions with other viral components of the reverse transcription initiation complex. Studies involving complementation between integration- and DNA synthesis-defective IN mutants further support this conclusion and reveal that the highly conserved HHCC motif of IN is important for both activities. These findings provide important new insights into IN function and reverse transcription in the context of the nucleoprotein reverse transcription complex within the infected cell. Moreover, they validate a novel approach that obviates the need to mutate Gag-Pol in order to study the role of its individual mature components at the virus replication level. PMID- 9971796 TI - The putative polymerase sequence of infectious salmon anemia virus suggests a new genus within the Orthomyxoviridae. AB - The infectious salmon anemia virus (ISAV) is an orthomyxovirus-like virus infecting teleosts. The disease caused by this virus has had major economic consequences for the Atlantic salmon farming industry in Norway, Canada, and Scotland. In this work, we report the cloning and sequencing of an ISAV-specific cDNA comprising 2,245 bp with an open reading frame coding for a predicted protein with a calculated molecular weight of 80.5 kDa. The putative protein sequence shows the core polymerase motifs characteristic of all viral RNA dependent RNA polymerases. Comparison of the conserved motifs with the corresponding regions of other segmented negative-stranded RNA viruses shows a closer relationship with members of the Orthomyxoviridae than with viruses in other families. The putative ISAV polymerase protein (PB1) has a length of 708 amino acids, a charge of +22 at neutral pH, and a pI of 9.9, which are consistent with the properties of the PB1 proteins of other members of the family. Calculations of the distances between the different PB1 proteins indicate that the ISAV is distantly related to the other members of the family but more closely related to the influenza viruses than to the Thogoto viruses. Based on these and previously published results, we propose that the ISAV comprises a new, fifth genus in the Orthomyxoviridae. PMID- 9971797 TI - Suppressor mutations within the core binding factor (CBF/AML1) binding site of a T-cell lymphomagenic retrovirus. AB - The transcriptional enhancer of the lymphomagenic mouse retrovirus SL3 contains a binding site for the transcription factor core binding factor (CBF; also called AML1, PEBP2, and SEF1). The SL3 CBF binding site is called the core. It differs from the core of the weakly lymphomagenic mouse retrovirus Akv by one nucleotide (the sequences are TGTGGTTAA and TGTGGTCAA, respectively). A mutant virus called SAA that was identical to SL3 except that its core was mutated to the Akv sequence was only moderately attenuated for lymphomagenicity. In most SAA infected mice, tumor proviruses contained either reversions of the original mutation or one of two novel core sequences. In 20% of the SAA-infected mice, tumor proviruses retained the original SAA/Akv core mutation but acquired one of two additional mutations (underlined), TGCGGTCAA or TGTGGTCTA, that generated core elements called So and T*, respectively. We tested whether the novel base changes in the So and T* cores were suppressor mutations. SL3 mutants that contained So or T* cores in place of the wild-type sequence were generated. These viruses induced T-cell lymphomas in mice more quickly than SAA. Therefore, the mutations in the So and T* cores are indeed second-site suppressor mutations. The suppressor mutations increased CBF binding in vitro and transcriptional activity of the viral long terminal repeats (LTRs) in T lymphocytes to levels comparable to those of SL3. Thus, CBF binding was increased by any of three different nucleotide changes within the sequence of the SAA core. Increased CBF binding resulted in increased LTR transcriptional activity in T cells and in increased viral lymphomagenicity. PMID- 9971798 TI - Extensive mutagenesis of the hepatitis B virus core gene and mapping of mutations that allow capsid formation. AB - We generated a large number of mutations in the hepatitis B virus (HBV) core gene inserted into a bacterial expression vector. The new mutagenesis procedure generated deletions and insertions (as sequence repeats) of various lengths at random positions between M1 and E145 but not substitutions. The R-rich 30-amino acid C-terminal domain was not analyzed. A total of 50,000 colonies were tested with a polyclonal human serum for the expression of hepatitis B core or e antigen. A total of 110 mutants randomly chosen from 1,500 positive colonies were genotyped. Deletions and insertions were clustered in four regions: D2 to E14, corresponding to the N-terminal loop in a model for the core protein fold (B. Bottcher, S. A. Wynne, and R. A. Crowther, Nature 386:88-91, 1997); V27 to P50 (second loop); L60 to V86 (upper half of the alpha helix forming the N-terminal part of the spike and the tip of the spike); and V124 to L140 (C-terminal part of the C-terminal helix and downstream loop). Deletions or insertions in the remaining parts of the molecule forming the compact center of the fold seemed to destabilize the protein. Of the 110 mutations, 38 allowed capsid formation in Escherichia coli. They mapped exclusively to nonhelical regions of the proposed fold. The mutations form a basis for subsequent analysis of further functions of the HBV core protein in the viral life cycle. PMID- 9971799 TI - Transcription of herpes simplex virus immediate-early and early genes is inhibited by roscovitine, an inhibitor specific for cellular cyclin-dependent kinases. AB - Although herpes simplex virus (HSV) replicates in noncycling as well as cycling cells, including terminally differentiated neurons, it has recently been shown that viral replication requires the activities of cellular cyclin-dependent kinases (cdks) (L. M. Schang, J. Phillips, and P. A. Schaffer, J. Virol. 72:5626 5637, 1998). Since we were unable to isolate HSV mutants resistant to two cdk inhibitors, Olomoucine and Roscovitine (Rosco), we hypothesized that cdks may be required for more than one viral function during HSV replication. In the experiments presented here, we tested this hypothesis by measuring the efficiency of (i) viral replication; (ii) expression of selected immediate-early (IE) (ICP0 and ICP4), early (E) (ICP8 and TK), and late (L) (gC) genes; and (iii) viral DNA synthesis in infected cultures to which Rosco was added after IE or IE and E proteins had already been synthesized. Rosco inhibited HSV replication, transcription of IE and E genes, and viral DNA synthesis when added at 1, 2, or 6 h postinfection or after release from a 6-h cycloheximide block. Transcription of a representative L gene, gC, was also inhibited by Rosco under all conditions examined. We conclude from these studies that cellular cdks are required for transcription of E as well as IE genes. In contrast, steady-state levels of at least one cellular housekeeping gene were not affected by Rosco. The requirement of viral IE and E transcription for cellular cdks may reflect either a requirement for specific cdk-activated cellular and/or viral transcription factors or a more global requirement for cdks in the transcriptional activation of the viral genome. PMID- 9971800 TI - African swine fever virus infection induces tumor necrosis factor alpha production: implications in pathogenesis. AB - We have analyzed the production of tumor necrosis factor alpha (TNF-alpha) induced by in vitro infection with African swine fever (ASF) virus (ASFV) and the systemic and local release of this inflammatory cytokine upon in vivo infection. An early increase in TNF-alpha mRNA expression was detected in ASFV-infected alveolar macrophages, and high levels of TNF-alpha protein were detected by ELISA in culture supernatants from these cells. When animals were experimentally infected with a virulent isolate (E-75), enhanced TNF-alpha expression in mainly affected organs correlated with viral protein expression. Finally, elevated levels of TNF-alpha were detected in serum, corresponding to the onset of clinical signs. TNF-alpha has been reported to be critically involved in the pathogenesis of major clinical events in ASF, such as intravascular coagulation, tissue injury, apoptosis, and shock. In the present study, TNF-alpha containing supernatants from ASFV-infected cultures induced apoptosis in uninfected lymphocytes; this effect was partially abrogated by preincubation with an anti TNF-alpha specific antibody. These results suggest a relevant role for TNF-alpha in the pathogenesis of ASF. PMID- 9971801 TI - Capsid structure of simian cytomegalovirus from cryoelectron microscopy: evidence for tegument attachment sites. AB - We have used cryoelectron microscopy and image reconstruction to study B-capsids recovered from both the nuclear and the cytoplasmic fractions of cells infected with simian cytomegalovirus (SCMV). SCMV, a representative betaherpesvirus, could thus be compared with the previously described B-capsids of the alphaherpesviruses, herpes simplex virus type 1 (HSV-1) and equine herpesvirus 1 (EHV-1), and of channel catfish virus, an evolutionarily remote herpesvirus. Nuclear B-capsid architecture is generally conserved with SCMV, but it is 4% larger in inner radius than HSV-1, implying that its approximately 30% larger genome should be packed more tightly. Isolated SCMV B-capsids retain a relatively well preserved inner shell (or "small core") of scaffolding-assembly protein, whose radial-density profile indicates that this protein is approximately 16-nm long and consists of two domains connected by a low-density linker. As with HSV 1, the hexons but not the pentons of the major capsid protein (151 kDa) bind the smallest capsid protein (approximately 8 kDa). Sodium dodecyl sulfate polyacrylamide gel electrophoresis showed cytoplasmic B-capsid preparations to contain proteins similar in molecular weight to the basic phosphoprotein (approximately 119 kDa) and the matrix proteins (65 to 70 kDa). Micrographs revealed that these particles had variable amounts of surface-adherent material not present on nuclear B-capsids that we take to be tegument proteins. Cytoplasmic B-capsids were classified accordingly as lightly, moderately, or heavily tegumented. By comparing the three corresponding density maps with each other and with the nuclear B-capsid, two interactions were identified between putative tegument proteins and the capsid surface. One is between the major capsid protein and a protein estimated by electron microscopy to be 50 to 60 kDa; the other involves an elongated molecule estimated to be 100 to 120 kDa that is anchored on the triplexes, most likely on its dimer subunits. Candidates for the proteins bound at these sites are discussed. This first visualization of such linkages makes a step towards understanding the organization and functional rationale of the herpesvirus tegument. PMID- 9971802 TI - Intracellular redistribution of truncated La protein produced by poliovirus 3Cpro mediated cleavage. AB - The La autoantigen (also known as SS-B), a cellular RNA binding protein, may shuttle between the nucleus and cytoplasm, but it is mainly located in the nucleus. La protein is redistributed to the cytoplasm after poliovirus infection. An in vitro translation study demonstrated that La protein stimulated the internal initiation of poliovirus translation. In the present study, a part of the La protein was shown to be cleaved in poliovirus-infected HeLa cells, and this cleavage appeared to be mediated by poliovirus-specific protease 3C (3Cpro). Truncated La protein (dl-La) was produced in vitro from recombinant La protein by cleavage with purified 3Cpro at only one Gln358-Gly359 peptide bond in the 408 amino-acid (aa) sequence of La protein. The dl-La expressed in L cells was detected in the cytoplasm. However, green fluorescence protein linked to the C terminal 50-aa sequence of La protein was localized in the nucleus, suggesting that this C-terminal region contributes to the steady-state nuclear localization of the intact La protein in uninfected cells. The dl-La retained the enhancing activity of translation initiation driven by poliovirus RNA in rabbit reticulocyte lysates. These results suggest that La protein is cleaved by 3Cpro in the course of poliovirus infection and that the dl-La is redistributed to the cytoplasm. dl-La, as well as La protein, may play a role in stimulating the internal initiation of poliovirus translation in the cytoplasm. PMID- 9971803 TI - Two regions of simian virus 40 T antigen determine cooperativity of double hexamer assembly on the viral origin of DNA replication and promote hexamer interactions during bidirectional origin DNA unwinding. AB - Phosphorylation of simian virus 40 large tumor (T) antigen on threonine 124 is essential for viral DNA replication. A mutant T antigen (T124A), in which this threonine was replaced by alanine, has helicase activity, assembles double hexamers on viral-origin DNA, and locally distorts the origin DNA structure, but it cannot catalyze origin DNA unwinding. A class of T-antigen mutants with single amino-acid substitutions in the DNA binding domain (class 4) has remarkably similar properties, although these proteins are phosphorylated on threonine 124, as we show here. By comparing the DNA binding properties of the T124A and class 4 mutant proteins with those of the wild type, we demonstrate that mutant double hexamers bind to viral origin DNA with reduced cooperativity. We report that T124A T-antigen subunits impair the ability of double hexamers containing the wild-type protein to unwind viral origin DNA, suggesting that interactions between hexamers are also required for unwinding. Moreover, the T124A and class 4 mutant T antigens display dominant-negative inhibition of the viral DNA replication activity of the wild-type protein. We propose that interactions between hexamers, mediated through the DNA binding domain and the N-terminal phosphorylated region of T antigen, play a role in double-hexamer assembly and origin DNA unwinding. We speculate that one surface of the DNA binding domain in each subunit of one hexamer may form a docking site that can interact with each subunit in the other hexamer, either directly with the N-terminal phosphorylated region or with another region that is regulated by phosphorylation. PMID- 9971804 TI - Measles virus infection induces terminal differentiation of human thymic epithelial cells. AB - Measles virus infection induces a profound immunosuppression that may lead to serious secondary infections and mortality. In this report, we show that the human cortical thymic epithelial cell line is highly susceptible to measles virus infection in vitro, resulting in infectious viral particle production and syncytium formation. Measles virus inhibits thymic epithelial cell growth and induces an arrest in the G0/G1 phases of the cell cycle. Moreover, we show that measles virus induces a progressive thymic epithelial cell differentiation process: attached measles virus-infected epithelial cells correspond to an intermediate state of differentiation while floating cells, recovered from cell culture supernatants, are fully differentiated. Measles virus-induced thymic epithelial cell differentiation is characterized by morphological and phenotypic changes. Measles virus-infected attached cells present fusiform and stellate shapes followed by a loss of cell-cell contacts and a shift from low- to high molecular-weight keratin expression. Measles virus infection induces thymic epithelial cell apoptosis in terminally differentiated cells, revealed by the condensation and degradation of DNA in measles virus-infected floating thymic epithelial cells. Because thymic epithelial cells are required for the generation of immunocompetent T lymphocytes, our results suggest that measles virus-induced terminal differentiation of thymic epithelial cells may contribute to immunosuppression, particularly in children, in whom the thymic microenvironment is of critical importance for the development and maturation of a functional immune system. PMID- 9971805 TI - Modulation of nuclear localization of the influenza virus nucleoprotein through interaction with actin filaments. AB - The influenza virus genome is transcribed in the nuclei of infected cells but assembled into progeny virions in the cytoplasm. This is reflected in the cellular distribution of the virus nucleoprotein (NP), a protein which encapsidates genomic RNA to form ribonucleoprotein structures. At early times postinfection NP is found in the nucleus, but at later times it is found predominantly in the cytoplasm. NP contains several sequences proposed to act as nuclear localization signals (NLSs), and it is not clear how these are overridden to allow cytoplasmic accumulation of the protein. We find that NP binds tightly to filamentous actin in vitro and have identified a cluster of residues in NP essential for the interaction. Complexes containing RNA, NP, and actin could be formed, suggesting that viral ribonucleoproteins also bind actin. In cells, exogenously expressed NP when expressed at a high level partitioned to the cytoplasm, where it associated with F-actin stress fibers. In contrast, mutants unable to bind F-actin efficiently were imported into the nucleus even under conditions of high-level expression. Similarly, nuclear import of NLS-deficient NP molecules was restored by concomitant disruption of F-actin binding. We propose that the interaction of NP with F-actin causes the cytoplasmic retention of influenza virus ribonucleoproteins. PMID- 9971806 TI - Kinetics of Kaposi's sarcoma-associated herpesvirus gene expression. AB - Herpesvirus gene expression can be classified into four distinct kinetic stages: latent, immediate early, early, and late. Here we characterize the kinetic class of a group of 16 Kaposi's sarcoma-associated herpesvirus (KSHV)/human herpesvirus 8 genes in a cultured primary effusion cell line and examine the expression of a subset of these genes in KS biopsies. Expression of two latent genes, LANA and vFLIP, was constitutive and was not induced by chemicals that induce the lytic cycle in primary effusion lymphoma (PEL) cell lines. An immediate-early gene, Rta (open reading frame 50 [ORF50]), was induced within 4 h of the addition of n butyrate, and its 3.6-kb mRNA was resistant to inhibition by cycloheximide. Early genes, including K3 and K5 that are homologues of the "immediate-early" gene of bovine herpesvirus 4, K8 that is a positional homologue of Epstein-Barr virus BZLF1, vMIP II, vIL-6, and polyadenylated nuclear (PAN) RNA, appeared 8 to 13 h after chemical induction. A second group of early genes that were slightly delayed in their appearance included viral DHFR, thymidylate synthase, vMIP I, G protein-coupled receptor, K12, vBcl2, and a lytic transcript that overlapped LANA. The transcript of sVCA (ORF65), a late gene whose expression was abolished by Phosphonoacetic acid, an inhibitor of KSHV DNA replication, did not appear until 30 h after induction. Single-cell assays indicated that the induction of lytic cycle transcripts resulted from the recruitment of additional cells into the lytic cycle. In situ hybridization of KS biopsies showed that about 3% of spindle-shaped tumor cells expressed Rta, ORF K8, vIL-6, vMIP I, vBcl-2, PAN RNA, and sVCA. Our study shows that several KSHV-encoded homologues of cellular cytokines, chemokines, and antiapoptotic factors are expressed during the viral lytic cycle in PEL cell lines and in KS biopsies. The lytic cycle of KSHV, probably under the initial control of the KSHV/Rta gene, may directly contribute to tumor pathogenesis. PMID- 9971807 TI - Hypoxia blocks in vivo initiation of simian virus 40 replication at a stage preceding origin unwinding. AB - Simian virus 40 (SV40)-infected CV1 cells transiently exposed to hypoxia show a burst of viral replication immediately after reoxygenation. DNA precursor incorporation and analysis of growing daughter strands by alkaline sedimentation demonstrated that SV40 DNA synthesis began with a lag of about 3 to 5 min after reoxygenation followed by a largely synchronous viral replication round. Viral RNA-DNA primers complementary to the SV40 origin region were not detectable before 3 min upon reoxygenation. A distinct form of circular closed, supercoiled SV40 DNA was detectable as soon as 3 min after reoxygenation but not under hypoxia. Sensitivity to the DNA nuclease Bal 31 and migration behavior in chloroquine-containing agarose gels suggested that this DNA species was highly underwound compared to other SV40 topoisomers and was probably related to the highly underwound form U DNA first described by Dean et al. (F. B. Dean, P. Bullock, Y. Murakami, C. R. Wobbe, L. Weissbach, and J. Hurwitz, Proc. Natl. Acad. Sci. USA 84:16-20, 1987), in vitro. 3'-OH ends of presumed RNA-DNA primers could be detected in form U by 3' end labeling with T7 polymerase. Addition of aphidicolin to the cells before reoxygenation led to a pronounced accumulation of form U DNA containing RNA-DNA primers. In vivo pulse-chase kinetic studies performed with aphidicolin-treated SV40-infected cells showed that form U is an initial intermediate of SV40 DNA replication which matures into higher-molecular weight replication intermediates and into SV40 form I DNA after removal of the inhibitor. These results suggest that in vivo initiation of SV40 replication is arrested by hypoxia before origin unwinding and primer synthesis. PMID- 9971808 TI - Adenovirus type 5 E4orf3 protein relieves p53 inhibition by E1B-55-kilodalton protein. AB - The E1B-55-kDa protein of adenovirus type 5 and the p53 tumor suppressor gene product form a complex that localizes to the cytoplasm, thereby downregulating p53's transcriptional activity. The E4orf6 protein binds and relocalizes E1B-55 kDa, and the proteins act synergistically to inactivate p53. We show that another adenovirus E4 gene product, E4orf3, is also sufficient to relocalize E1B-55-kDa from the cytoplasm to the nucleus. Both proteins are then found in discrete nuclear structures (tracks) that are known to contain components of the promyelocytic leukemia-associated nuclear structure. Simultaneously, p53 is dissociated from E1B-55-kDa and is found evenly distributed over the nucleoplasm. In the presence of E4orf3, p53-dependent transcriptional activity is no longer repressed by E1B-55-kDa. When E1B-55-kDa is coexpressed with E4orf3 and E4orf6, E1B-55-kDa is found to colocalize with E4orf6 rather than E4orf3. In parallel, p53 is inhibited and degraded by the combination of E1B-55-kDa and E4orf6, regardless of coexpressed E4orf3. This suggests that the effects of E4orf6 on E1B 55-kDa overrule the actions of E4orf3. When cells are infected with virus expressing E4orf3 but not E4orf6, E1B is found in the cell nucleus and p53 enters the virus replication centers. After infection with wild-type adenovirus, E4orf3 is expressed before E4orf6 and E1B temporarily colocalizes with E4orf3 in nuclear tracks before associating with E4orf6. We propose that during adenovirus infection, the E4orf3 protein transiently liberates p53 from its association with E1B-55-kDa. Subsequently, p53 is inactivated and degraded by the combination of E1B-55-kDa and E4orf6. PMID- 9971809 TI - Sequence analysis and expression of the attachment and fusion proteins of canine distemper virus wild-type strain A75/17. AB - The biological properties of wild-type A75/17 and cell culture-adapted Onderstepoort canine distemper virus differ markedly. To learn more about the molecular basis for these differences, we have isolated and sequenced the protein coding regions of the attachment and fusion proteins of wild-type canine distemper virus strain A75/17. In the attachment protein, a total of 57 amino acid differences were observed between the Onderstepoort strain and strain A75/17, and these were distributed evenly over the entire protein. Interestingly, the attachment protein of strain A75/17 contained an extension of three amino acids at the C terminus. Expression studies showed that the attachment protein of strain A75/17 had a higher apparent molecular mass than the attachment protein of the Onderstepoort strain, in both the presence and absence of tunicamycin. In the fusion protein, 60 amino acid differences were observed between the two strains, of which 44 were clustered in the much smaller F2 portion of the molecule. Significantly, the AUG that has been proposed as a translation initiation codon in the Onderstepoort strain is an AUA codon in strain A75/17. Detailed mutation analyses showed that both the first and second AUGs of strain A75/17 are the major translation initiation sites of the fusion protein. Similar analyses demonstrated that, also in the Onderstepoort strain, the first two AUGs are the translation initiation codons which contribute most to the generation of precursor molecules yielding the mature form of the fusion protein. PMID- 9971810 TI - In vitro assembly properties of human immunodeficiency virus type 1 Gag protein lacking the p6 domain. AB - Human immunodeficiency virus type 1 (HIV-1) normally assembles into particles of 100 to 120 nm in diameter by budding through the plasma membrane of the cell. The Gag polyprotein is the only viral protein that is required for the formation of these particles. We have used an in vitro assembly system to examine the assembly properties of purified, recombinant HIV-1 Gag protein and of Gag missing the C terminal p6 domain (Gag Deltap6). This system was used previously to show that the CA-NC fragment of HIV-1 Gag assembled into cylindrical particles. We now report that both HIV-1 Gag and Gag Deltap6 assemble into small, 25- to 30-nm diameter spherical particles in vitro. The multimerization of Gag Deltap6 into units larger than dimers and the formation of spherical particles required nucleic acid. Removal of the nucleic acid with NaCl or nucleases resulted in the disruption of the multimerized complexes. We conclude from these results that (i) N-terminal extension of HIV-1 CA-NC to include the MA domain results in the formation of spherical, rather than cylindrical, particles; (ii) nucleic acid is required for the assembly and maintenance of HIV-1 Gag Deltap6 virus-like particles in vitro and possibly in vivo; (iii) a wide variety of RNAs or even short DNA oligonucleotides will support assembly; (iv) protein-protein interactions within the particle must be relatively weak; and (v) recombinant HIV 1 Gag Deltap6 and nucleic acid are not sufficient for the formation of normal sized particles. PMID- 9971811 TI - Dissecting the immune response to moloney murine sarcoma/leukemia virus-induced tumors by means of a DNA vaccination approach. AB - The intramuscular inoculation of Moloney murine sarcoma/leukemia (M-MSV/M-MuLV) retroviral complex gives rise to sarcomas that undergo spontaneous regression due to the induction of a strong immune reaction mediated primarily by cytotoxic T lymphocytes (CTL). We used a DNA-based vaccination approach to dissect the CTL response against the Gag and Env proteins of M-MSV/M-MuLV in C57BL/6 (B6) mice and to evaluate whether plasmid DNA-immunized mice would be protected against a subsequent challenge with syngeneic tumor cells expressing the viral antigens. Intramuscular DNA vaccination induced CTL against both Gag and Env proteins. A detailed analysis of epitopes recognized by CTL generated in mice inoculated with the whole virus and with the Gag-expressing plasmid confirmed the presence of an immunodominant peptide in the leader sequence of Gag protein (Gag85-93, CCLCLTVFL) that is identical to that described in B6 mice immunized with Friend MuLV-induced leukemia cells. Moreover, CTL generated by immunization with the Env encoding plasmid recognized a subdominant Env peptide (Env189-196, SSWDFITV), originally described in the B6.CH-2(bm13) mutant strain. B6 mice immunized with the Gag-expressing plasmid were fully protected against a lethal tumor challenge with M-MuLV-transformed MBL-2 leukemia cells, while vaccination with the Env expressing plasmid resulted in rejection of the tumor in 44% of the mice and in increased survival of an additional 17% of the animals. Taken together, these results indicate the existence of a hierarchy in the capacity of different structural viral proteins to induce a protective immune response against retrovirus-induced tumors. PMID- 9971812 TI - Tomato spotted wilt virus particle morphogenesis in plant cells. AB - A model for the maturation of tomato spotted wilt virus (TSWV) particles is proposed, mainly based on results with a protoplast infection system, in which the chronology of different maturation events could be determined. By using specific monoclonal and polyclonal antisera in immunofluorescence and electron microscopy, the site of TSWV particle morphogenesis was determined to be the Golgi system. The viral glycoproteins G1 and G2 accumulate in the Golgi prior to a process of wrapping, by which the viral nucleocapsids obtain a double membrane. In a later stage of the maturation, these doubly enveloped particles fuse to each other and to the endoplasmic reticulum to form singly enveloped particles clustered in membranes. Similarities and differences between the maturation of animal-infecting (bunya)viruses and plant-infecting tospoviruses are discussed. PMID- 9971813 TI - The reovirus mutant tsA279 L2 gene is associated with generation of a spikeless core particle: implications for capsid assembly. AB - Previous studies which used intertypic reassortants of the wild-type reovirus serotype 1 Lang and the temperature-sensitive (ts) serotype 3 mutant clone tsA279 identified two ts lesions; one lesion, in the M2 gene segment, was associated with defective transmembrane transport of restrictively assembled virions (P. R. Hazelton and K. M. Coombs, Virology 207:46-58, 1995). In the present study we show that the second lesion, in the L2 gene segment, which encodes the lambda2 protein, is associated with the accumulation of a core-like particle defective for the lambda2 pentameric spike. Physicochemical, biochemical, and immunological studies showed that these structures were deficient for genomic double-stranded RNA, the core spike protein lambda2, and the minor core protein micro2. Core particles with the lambda2 spike structure accumulated after temperature shift down from a restrictive to a permissive temperature in the presence of cycloheximide. These data suggest the spike-deficient, core-like particle is an assembly intermediate in reovirus morphogenesis. The existence of this naturally occurring primary core structure suggests that the core proteins lambda1, lambda3, and sigma2 interact to initiate the process of virion capsid assembly through a dodecahedral mechanism. The next step in the proposed capsid assembly model would be the association of the minor core protein mu2, either preceding or collateral to the condensation of the lambda2 pentameric spike at the apices of the primary core structure. The assembly pathway of the reovirus double capsid is further elaborated when these observations are combined with structures identified in other studies. PMID- 9971814 TI - Identification of retroviral late domains as determinants of particle size. AB - Retroviral Gag proteins, in the absence of any other viral products, induce budding and release of spherical, virus-like particles from the plasma membrane. Gag-produced particles, like those of authentic retrovirions, are not uniform in diameter but nevertheless fall within a fairly narrow distribution of sizes. For the human immunodeficiency virus type 1 (HIV-1) Gag protein, we recently reported that elements important for controlling particle size are contained within the C terminal region of Gag, especially within the p6 sequence (L. Garnier, L. Ratner, B. Rovinski, S.-X. Cao, and J. W. Wills, J. Virol. 72:4667-4677, 1998). Deletions and substitutions throughout this sequence result in the release of very large particles. Because the size determinant could not be mapped to any one of the previously defined functions within p6, it seemed likely that its activity requires the overall proper folding of this region of Gag. This left open the possibility of the size determinant residing in a subdomain of p6, and in this study, we examined whether the late domain (the region of Gag that is critical for the virus-cell separation step) is involved in controlling particle size. We found that particles of normal size are produced when p6 is replaced with the totally unrelated late domain sequences from Rous sarcoma virus (contained in its p2b sequence) or equine infectious anemia virus (contained in p9). In addition, we found that the large particles released in the absence of p6 require the entire CA and adjacent spacer peptide sequences, whereas these internal sequences of HIV-1 Gag are not needed for budding (or proper size) when a late domain is present. Thus, it appears the requirements for budding are very different in the presence and absence of p6. PMID- 9971815 TI - Three distinct regions of the murine gammaherpesvirus 68 genome are transcriptionally active in latently infected mice. AB - The program(s) of gene expression operating during murine gammaherpesvirus 68 (gammaHV68) latency is undefined, as is the relationship between gammaHV68 latency and latency of primate gammaherpesviruses. We used a nested reverse transcriptase PCR strategy (sensitive to approximately one copy of gammaHV68 genome for each genomic region tested) to screen for the presence of viral transcripts in latently infected mice. Based on the positions of known latency associated genes in other gammaherpesviruses, we screened for the presence of transcripts corresponding to 11 open reading frames (ORFs) in the gammaHV68 genome in RNA from spleens and peritoneal cells of latently infected B-cell deficient (MuMT) mice which have been shown contain high levels of reactivable latent gammaHV68 (K. E. Weck, M. L. Barkon, L. I. Yoo, S. H. Speck, and H. W. Virgin, J. Virol. 70:6775-6780, 1996). To control for the possible presence of viral lytic activity, we determined that RNA from latently infected peritoneal and spleen cells contained few or no detectable transcripts corresponding to seven ORFs known to encode viral gene products associated with lytic replication. However, we did detect low-level expression of transcripts arising from the region of gene 50 (encoding the putative homolog of the Epstein-Barr virus BRLF1 transactivator) in peritoneal but not spleen cells. Latently infected peritoneal cells consistently scored for expression of RNA derived from 4 of the 11 candidate latency-associated ORFs examined, including the regions of ORF M2, ORF M11 (encoding v-bcl-2), gene 73 (a homolog of the Kaposi's sarcoma-associated herpesvirus [human herpesvirus 8] gene encoding latency-associated nuclear antigen), and gene 74 (encoding a G-protein coupled receptor homolog, v-GCR). Latently infected spleen cells consistently scored positive for RNA derived from 3 of the 11 candidate latency-associated ORFs examined, including ORF M2, ORF M3, and ORF M9. To further characterize transcription of these candidate latency associated ORFs, we examined their transcription in lytically infected fibroblasts by Northern analysis. We detected abundant transcription from regions of the genome containing ORF M3 and ORF M9, as well as the known lytic-cycle genes. However, transcription of ORF M2, ORF M11, gene 73, and gene 74 was barely detectable in lytically infected fibroblasts, consistent with a role of these viral genes during latent infection. We conclude that (i) we have identified several candidate latency genes of murine gammaHV68, (ii) expression of genes during latency may be different in different organs, consistent with multiple latency programs and/or multiple cellular sites of latency, and (iii) regions of the viral genome (v-bcl-2 gene, v-GCR gene, and gene 73) are transcribed during latency with both gammaHV68 and primate gammaherpesviruses. The implications of these findings for replacing previous operational definitions of gammaHV68 latency with a molecular definition are discussed. PMID- 9971816 TI - Comparison of the transcription and replication strategies of marburg virus and Ebola virus by using artificial replication systems. AB - The members of the family Filoviridae, Marburg virus (MBGV) and Ebola virus (EBOV), are very similar in terms of morphology, genome organization, and protein composition. To compare the replication and transcription strategies of both viruses, an artificial replication system based on the vaccinia virus T7 expression system was established for EBOV. Specific transcription and replication of an artificial monocistronic minireplicon was demonstrated by reporter gene expression and detection of the transcribed and replicated RNA species. As it was shown previously for MBGV, three of the four EBOV nucleocapsid proteins, NP, VP35, and L, were essential and sufficient for replication. In contrast to MBGV, EBOV-specific transcription was dependent on the presence of the fourth nucleocapsid protein, VP30. When EBOV VP30 was replaced by MBGV VP30, EBOV-specific transcription was observed but with lower efficiency. Exchange of NP, VP35, and L between the two replication systems did not lead to detectable reporter gene expression. It was further observed that neither MBGV nor EBOV were able to replicate the heterologous minigenomes. A chimeric minigenome, however, containing the EBOV leader and the MBGV trailer was encapsidated, replicated, transcribed, and packaged by both viruses. PMID- 9971817 TI - Primary human immunodeficiency virus type 2 (HIV-2) isolates, like HIV-1 isolates, frequently use CCR5 but show promiscuity in coreceptor usage. AB - Coreceptor usage of primary human immunodeficiency virus type 1 (HIV-1) isolates varies according to biological phenotype. The chemokine receptors CCR5 and CXCR4 are the major coreceptors that, together with CD4, govern HIV-1 entry into cells. Since CXCR4 usage determines the biological phenotype for HIV-1 isolates and is more frequent in patients with immunodeficiency, it may serve as a marker for viral virulence. This possibility prompted us to study coreceptor usage by HIV-2, known to be less pathogenic than HIV-1. We tested 11 primary HIV-2 isolates for coreceptor usage in human cell lines: U87 glioma cells, stably expressing CD4 and the chemokine receptor CCR1, CCR2b, CCR3, CCR5, or CXCR4, and GHOST(3) osteosarcoma cells, coexpressing CD4 and CCR5, CXCR4, or the orphan receptor Bonzo or BOB. The indicator cells were infected by cocultivation with virus producing peripheral blood mononuclear cells and by cell-free virus. Our results show that 10 of 11 HIV-2 isolates were able to efficiently use CCR5. In contrast, only two isolates, both from patients with advanced disease, used CXCR4 efficiently. These two isolates also promptly induced syncytia in MT-2 cells, a pattern described for HIV-1 isolates that use CXCR4. Unlike HIV-1, many of the HIV-2 isolates were promiscuous in their coreceptor usage in that they were able to use, apart from CCR5, one or more of the CCR1, CCR2b, CCR3, and BOB coreceptors. Another difference between HIV-1 and HIV-2 was that the ability to replicate in MT-2 cells appeared to be a general property of HIV-2 isolates. Based on BOB mRNA expression in MT-2 cells and the ability of our panel of HIV-2 isolates to use BOB, we suggest that HIV-2 can use BOB when entering MT-2 cells. The results indicate no obvious link between viral virulence and the ability to use a multitude of coreceptors. PMID- 9971819 TI - Alterations to both the primary and predicted secondary structure of stem-loop IIIc of the hepatitis C virus 1b 5' untranslated region (5'UTR) lead to mutants severely defective in translation which cannot be complemented in trans by the wild-type 5'UTR sequence. AB - Cap-independent translation of the hepatitis C virus (HCV) genomic RNA is mediated by an internal ribosome entry site (IRES) within the 5' untranslated region (5'UTR) of the virus RNA. To investigate the effects of alterations to the primary sequence of the 5'UTR on IRES activity, a series of HCV genotype 1b (HCV 1b) variant IRES elements was generated and cloned into a bicistronic reporter construct. Changes from the prototypic HCV-1b 5'UTR sequence were identified at various locations throughout the 5'UTR. The translation efficiencies of these IRES elements were examined by an in vivo transient expression assay in transfected BHK-21 cells and were found to range from 0.4 to 95.8% of the activity of the prototype HCV-1b IRES. Further mutational analysis of the three single-point mutants most severely defective in activity, whose mutations were all located in or near stem-loop IIIc, demonstrated that both the primary sequence and the maintenance of base pairing within this stem structure were critical for HCV IRES function. Complementation studies indicated that defective mutants containing either point mutations or major deletions within the IRES elements could not be complemented in trans by a wild-type IRES. PMID- 9971820 TI - Identification of an active reverse transcriptase enzyme encoded by a human endogenous HERV-K retrovirus. AB - Of the numerous endogenous retroviral elements that are present in the human genome, the abundant HERV-K family is distinct because several members are transcriptionally active and coding for biologically active proteins. A detailed phylogeny of the HERV-K family based on the partial sequence of the reverse transcriptase (RT) gene revealed a high incidence of an intact RT open reading frame within the HML-2 subgroup of HERV-K elements. In this study, we report the cloning of six full-length HML-2 RT genes, of which five contain an uninterrupted open reading frame. The RT enzymes were expressed as glutathione S-transferase fusion proteins in Escherichia coli, and several HERV-K RT enzymes demonstrated polymerase as well as RNase H activity. Several biochemical properties of the RT polymerase were analyzed, including the template requirements and optimal reaction conditions (temperature, type of divalent cation). Inspection of the nucleotide sequence of the HERV-K RT genes demonstrated a mosaic structure, suggesting that a high level of genetic recombination has occurred in this virus family, which is a hallmark of replication by means of reverse transcription. The selective pressure to maintain the RT coding potential is illustrated by the sequence of a particular HERV-K isolate that contains three 1-nucleotide deletions within a small RT segment, thus maintaining the open reading frame. These combined results may suggest that these endogenous RT enzymes still have a biological function. It is possible that the RT activity was involved in the spread of this major class of retroelements by retrotransposition, and in fact it cannot be excluded that this retrovirus group is still mobile. The endogenous RT activity may also have been involved in the shaping of the human genome, e.g., by formation of pseudogenes. PMID- 9971818 TI - V3 recombinants indicate a central role for CCR5 as a coreceptor in tissue infection by human immunodeficiency virus type 1. AB - Binding of the human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein gp120 to both CD4 and one of several chemokine receptors (coreceptors) permits entry of virus into target cells. Infection of tissues may establish latent viral reservoirs as well as cause direct pathologic effects that manifest as clinical disease such as HIV-associated dementia. We sought to identify the critical coreceptors recognized by HIV-1 tissue-derived strains as well as to correlate these coreceptor preferences with site of infection and dementia diagnosis. To reconstitute coreceptor use, we cloned HIV-1 envelope V3 sequences encoding the primary determinants of coreceptor specificity from 13 brain-derived and 6 colon derived viruses into an isogenic (NL4-3) viral background. All V3 recombinants utilized the chemokine receptor CCR5 uniformly and efficiently as a coreceptor but not CXCR4, BOB/GPR15, or Bonzo/STRL33. Other receptors such as CCR3, CCR8, and US28 were inefficiently and variably used as coreceptors by various envelopes. CCR5 without CD4 present did not allow for detectable infection by any of the tested recombinants. In contrast to the pathogenic switch in coreceptor specificity frequently observed in comparisons of blood-derived viruses early after HIV-1 seroconversion and after onset of AIDS, the characteristics of these V3 recombinants suggest that CCR5 is a primary coreceptor for brain- and colon derived viruses regardless of tissue source or diagnosis of dementia. Therefore, tissue infection may not depend significantly on viral envelope quasispeciation to broaden coreceptor range but rather selects for CCR5 use throughout disease progression. PMID- 9971821 TI - Myxoma virus encodes an alpha2,3-sialyltransferase that enhances virulence. AB - A 4.7-kb region of DNA sequence contained at the right end of the myxoma virus EcoRI-G2 fragment located 24 kb from the right end of the 163-kb genome has been determined. This region of the myxoma virus genome encodes homologs of the vaccinia virus genes A51R, A52R, A55R, A56R, and B1R; the myxoma virus gene equivalents have been given the prefix M. The MA55 gene encodes a protein belonging to the kelch family of actin-binding proteins, while the MA56 gene encodes a member of the immunoglobulin superfamily related to a variety of cellular receptors and adhesion molecules. A novel myxoma virus early gene, MST3N, is a member of the eukaryotic sialyltransferase gene family located between genes MA51 and MA52. Detergent lysates prepared from myxoma virus infected cell cultures contained a virally encoded sialyltransferase activity that catalyzed the transfer of sialic acid (Sia) from CMP-Sia to an asialofetuin glycoprotein acceptor. Analysis of the in vitro-sialylated glycoprotein acceptor by digestion with N-glycosidase F and by lectin binding suggested that the MST3N gene encodes an enzyme with Galbeta1,3(4)GlcNAc alpha2,3-sialyltransferase specificity for the N-linked oligosaccharide of glycoprotein. Lectin binding assays demonstrated that alpha2,3-sialyltransferase activity is expressed by several known leporipoxviruses that naturally infect Sylvilagus rabbits. The sialyltransferase is nonessential for myxoma virus replication in cell culture; however, disruption of the MST3N gene caused attenuation in vivo. The possible implications of the myxoma virus-expressed sialyltransferase in terms of the host's defenses against infection are discussed. PMID- 9971822 TI - U1 small nuclear ribonucleoprotein and splicing inhibition by the rous sarcoma virus negative regulator of splicing element. AB - Retroviruses require both spliced and unspliced RNA for replication. Accumulation of unspliced Rous sarcoma virus RNA is facilitated in part by a negative cis element in the gag region, termed the negative regulator of splicing (NRS), which serves to repress splicing of viral RNA but can also block splicing of heterologous introns. The NRS binds components of the splicing machinery including SR proteins, U1 and U2, small nuclear ribonucleoproteins (snRNPs) of the major splicing pathway, and U11 snRNP of the minor pathway, yet splicing does not normally occur from the NRS. A mutation that abolishes U11 binding (RG11) also abrogates NRS splicing inhibition, indicating that U11 is functionally important for NRS activity and suggesting that the NRS is recognized as a minor class 5' splice site (5' ss). We show here, using specific NRS mutations to disrupt U11 binding and coexpression of U11 snRNA genes harboring compensatory mutations, that the NRS U11 site is functional when paired with a minor-class 3' ss from the human P120 gene. Surprisingly, the expectation that the same NRS mutants would be defective for splicing inhibition proved false; splicing inhibition was as good as, if not better than, that for the wild-type NRS. Comparison of these new mutations with RG11 indicated that the latter may disrupt binding of a factor(s) other than U11. Our data suggest that this factor is U1 snRNP and that a U1 binding site that overlaps the U11 site is also disrupted by RG11. Analysis of mutations which selectively disrupted U1 or U11 binding indicated that splicing inhibition by the NRS correlates most strongly with U1 snRNP. Additionally, we show that U1 binding is facilitated by SR proteins that bind to the 5' half of the NRS, confirming an earlier proposal that this region is involved in recruiting snRNPs to the NRS. These data indicate a functional role for U1 in NRS-mediated splicing inhibition. PMID- 9971823 TI - Interaction between the negative regulator of splicing element and a 3' splice site: requirement for U1 small nuclear ribonucleoprotein and the 3' splice site branch point/pyrimidine tract. AB - The negative regulator of splicing (NRS) from Rous sarcoma virus suppresses viral RNA splicing and is one of several cis elements that account for the accumulation of large amounts of unspliced RNA for use as gag-pol mRNA and progeny virion genomic RNA. The NRS can also inhibit splicing of heterologous introns in vivo and in vitro. Previous data showed that the splicing factors SF2/ASF and U1, U2, and U11 small nuclear ribonucleoproteins (snRNPs) bind the NRS, and a correlation was established between SF2/ASF and U11 binding and activity, suggesting that these factors are important for function. These observations, and the finding that a large spliceosome-like complex (NRS-C) assembles on NRS RNA in nuclear extract, led to the proposal that the NRS is recognized as a minor-class 5' splice site. One model to explain NRS splicing inhibition holds that the NRS interacts nonproductively with and sequesters U2-dependent 3' splice sites. In this study, we provide evidence that the NRS interacts with an adenovirus 3' splice site. The interaction was dependent on the integrity of the branch point and pyrimidine tract of the 3' splice site, and it was sensitive to a mutation that was previously shown to abolish U11 snRNP binding and NRS function. However, further mutational analyses of NRS sequences have identified a U1 binding site that overlaps the U11 site, and the interaction with the 3' splice site correlated with U1, not U11, binding. These results show that the NRS can interact with a 3' splice site and suggest that U1 is of primary importance for NRS splicing inhibition. PMID- 9971824 TI - Interleukin-18 protects mice against acute herpes simplex virus type 1 infection. AB - We examined the effects of interleukin-18 (IL-18) in a mouse model of acute intraperitoneal infection with herpes simplex virus type 1 (HSV-1). Four days of treatment with IL-18 (from 2 days before infection to 1 day after infection) improved the survival rate of BALB/c, BALB/c nude, and BALB/c SCID mice, suggesting innate immunity. One day after infection, HSV-1 titers were higher in the peritoneal washing fluid of control BALB/c mice than in that of IL-18-treated mice. A genetic deficiency of gamma interferon (IFN-gamma), however, diminished the survival rate and the inhibition of HSV-1 growth at the injection site in the mice. Anti-asialo GM1 treatment had no influence on the protective effect of IL 18 in infected mice. IL-18 augmented IFN-gamma release in vitro by peritoneal cells from uninfected mice, while no appreciable IFN-gamma production was found in uninfected mice administered IL-18. Although IFN-gamma has the ability to induce nitric oxide (NO) production by various types of cells, administration of the NO synthase inhibitor NG-monomethyl-L-arginine resulted in superficial loss of the improved survival, but there was no influence on the inhibition of HSV-1 replication at the injection site in IL-18-treated mice. Based on these results, we propose that IFN-gamma produced before HSV-1 infection plays a key role as one of the IL-18-promoted protection mechanisms and that neither NK cells nor NO plays this role. PMID- 9971825 TI - In vivo addition of poly(A) tail and AU-rich sequences to the 3' terminus of the Sindbis virus RNA genome: a novel 3'-end repair pathway. AB - Alphaviruses are mosquito-transmitted RNA viruses that cause important diseases in both humans and livestock. Sindbis virus (SIN), the type species of the alphavirus genus, carries a 11.7-kb positive-sense RNA genome which is capped at its 5' end and polyadenylated at its 3' end. The 3' nontranslated region (3'NTR) of the SIN genome carries many AU-rich motifs, including a 19-nucleotide (nt) conserved element (3'CSE) and a poly(A) tail. This 3'CSE and the adjoining poly(A) tail are believed to regulate the synthesis of negative-sense RNA and genome replication in vivo. We have recently demonstrated that the SIN genome lacking the poly(A) tail was infectious and that de novo polyadenylation could occur in vivo (K. R. Hill, M. Hajjou, J. Hu, and R. Raju, J. Virol. 71:2693-2704, 1997). Here, we demonstrate that the 3'-terminal 29-nt region of the SIN genome carries a signal for possible cytoplasmic polyadenylation. To further investigate the polyadenylation signals within the 3'NTR, we generated a battery of mutant genomes with mutations in the 3'NTR and tested their ability to generate infectious virus and undergo 3' polyadenylation in vivo. Engineered SIN genomes with terminal deletions within the 19-nt 3'CSE were infectious and regained their poly(A) tail. Also, a SIN genome carrying the poly(A) tail but lacking a part or the entire 19-nt 3'CSE was also infectious. Sequence analysis of viruses generated from these engineered SIN genomes demonstrated the addition of a variety of AU-rich sequence motifs just adjacent to the poly(A) tail. The addition of AU-rich motifs to the mutant SIN genomes appears to require the presence of a significant portion of the 3'NTR. These results indicate the ability of alphavirus RNAs to undergo 3' repair and the existence of a pathway for the addition of AU-rich sequences and a poly(A) tail to their 3' end in the infected host cell. Most importantly, these results indicate the ability of alphavirus replication machinery to use a multitude of AU-rich RNA sequences abutted by a poly(A) motif as promoters for negative-sense RNA synthesis and genome replication in vivo. The possible roles of cytoplasmic polyadenylation machinery, terminal transferase-like enzymes, and the viral polymerase in the terminal repair processes are discussed. PMID- 9971826 TI - Hybrid frequencies confirm limit to coinfection in the RNA bacteriophage phi6. AB - Coinfection of the same host cell by multiple viruses may lead to increased competition for limited cellular resources, thus reducing the fitness of an individual virus. Selection should favor viruses that can limit or prevent coinfection, and it is not surprising that many viruses have evolved mechanisms to do so. Here we explore whether coinfection is limited in the RNA bacteriophage phi6 that infects Pseudomonas phaseolicola. We estimated the limit to coinfection in phi6 by comparing the frequency of hybrids produced by two marked phage strains to that predicted by a mathematical model based on differing limits to coinfection. Our results provide an alternative method for estimating the limit to coinfection and confirm a previous estimate between two to three phages per host cell. In addition, our data reveal that the rate of coinfection at low phage densities may exceed that expected through random Poisson sampling. We discuss whether phage phi6 has evolved an optimal limit that balances the costly and beneficial fitness effects associated with multiple infections. PMID- 9971827 TI - Mutant influenza viruses with a defective NS1 protein cannot block the activation of PKR in infected cells. AB - A short model genome RNA and also the genome RNA of influenza A virus bearing both 5'- and 3'-terminal common sequences activated the interferon-induced double stranded-RNA-dependent protein kinase, PKR, by stimulating autophosphorylation in vitro. The activated PKR catalyzed phosphorylation of the alpha subunit of eucaryotic translation initiation factor 2 (eIF2alpha). The NS1 protein efficiently eliminated the PKR-activating activity of these RNAs by binding to them. Two mutant NS1 proteins, each harboring a single amino acid substitution at different regions, exhibited temperature sensitivity in their RNA binding activity in the mutant virus-infected cell lysates as well as when they were prepared as fusion proteins expressed in bacteria. The virus strains carrying these mutant NS1 proteins exhibited temperature sensitivity in virus protein synthesis at the translational level, as reported previously, and could not repress the autophosphorylation of PKR developing during the virus growth, which is normally suppressed by a viral function(s). As a result, the level of eIF2alpha phosphorylation was elevated 2.5- to 3-fold. The defect in virus protein synthesis was well correlated with the level of phosphorylation of PKR and eIF2alpha. PMID- 9971828 TI - Moloney murine leukemia virus-induced preleukemic thymic atrophy and enhanced thymocyte apoptosis correlate with disease pathogenicity. AB - Moloney murine leukemia virus (M-MuLV) is a replication-competent, simple retrovirus that induces T-cell lymphoma with a mean latency of 3 to 4 months. During the preleukemic period (4 to 10 weeks postinoculation) a marked decrease in thymic size is apparent for M-MuLV-inoculated mice in comparison to age matched uninoculated mice. We were interested in studying whether the thymic regression was due to an increased rate of thymocyte apoptosis in the thymi of M MuLV-inoculated mice. Neonatal NIH/Swiss mice were inoculated subcutaneously (s.c.) with wild-type M-MuLV (approximately 10(5) XC PFU). Mice were sacrificed at 4 to 11 weeks postinoculation. Thymic single-cell suspensions were prepared and tested for apoptosis by two-parameter flow cytometry. Indications of apoptosis included changes in cell size and staining with 7-aminoactinomycin D or annexin V. The levels of thymocyte apoptosis were significantly higher in M-MuLV inoculated mice than in uninoculated control animals, and the levels of apoptosis were correlated with thymic atrophy. To test the relevance of enhanced thymocyte apoptosis to leukemogenesis, mice were inoculated with the Mo+PyF101 enhancer variant of M-MuLV. When inoculated intraperitoneally, a route that results in wild-type M-MuLV leukemogenesis, mice displayed levels of enhanced thymocyte apoptosis comparable to those seen with wild-type M-MuLV. However, in mice inoculated s.c., a route that results in attenuated leukemogenesis, significantly lower levels of apoptosis were observed. This supported a role for higher levels of thymocyte apoptosis in M-MuLV leukemogenesis. To examine the possible role of mink cell focus-forming (MCF) recombinant virus in raising levels of thymocyte apoptosis, MCF-specific focal immunofluorescence assays were performed on thymocytes from preleukemic mice inoculated with M-MuLV and Mo+PyF101 M-MuLV. The results indicated that infection of thymocytes by MCF virus recombinants is not required for the increased level of apoptosis and thymic atrophy. PMID- 9971829 TI - Interclass transmission and phyletic host tracking in murine leukemia virus related retroviruses. AB - Retroviruses are capable of infectious horizontal transmission between hosts, usually between individuals within a single species, although a number of probable zoonotic infections resulting from transmission between different species of placental mammals have also been reported. Despite these data, it remains unclear how often interspecies transmission events occur or whether their frequency is influenced by the evolutionary distance between host taxa. To address this problem we used PCR to amplify and characterize endogenous retroviruses related to the murine leukemia viruses. We show that members of this retroviral genus are harbored by considerably more organisms than previously thought and that phylogenetic analysis demonstrates that viruses isolated from a particular host class generally cluster together, suggesting that infectious virus horizontal transfer between vertebrate classes occurs only rarely. However, two recent instances of transmission of zoonotic infections between distantly related host organisms were identified. One, from mammals to birds, has led to a rapid adaptive radiation into other avian hosts. The other, between placental and marsupial mammals, involves viruses clustering with recently described porcine retroviruses, adding to concerns regarding the xenotransplantation of pig organs to humans. PMID- 9971830 TI - CCR2-64I polymorphism is not associated with altered CCR5 expression or coreceptor function. AB - A polymorphism in the gene encoding CCR2 is associated with a delay in progression to AIDS in human immunodeficiency virus (HIV)-infected individuals. The polymorphism, CCR2-64I, changes valine 64 of CCR2 to isoleucine. However, it is not clear whether the effect on AIDS progression results from the amino acid change or whether the polymorphism marks a genetically linked, yet unidentified mutation that mediates the effect. Because the gene encoding CCR5, the major coreceptor for HIV type 1 primary isolates, lies 15 kb 3' to CCR2, linked mutations in the CCR5 promoter or other regulatory sequences could explain the association of CCR2-64I with slowed AIDS pathogenesis. Here, we show that CCR2 64I is efficiently expressed on the cell surface but does not have dominant negative activity on CCR5 coreceptor function. A panel of peripheral blood mononuclear cells (PBMC) from uninfected donors representing the various CCR5/CCR2 genotypes was assembled. Activated primary CD4(+) T cells of CCR2 64I/64I donors expressed cell surface CCR5 at levels comparable to those of CCR2 +/+ donors. A slight reduction in CCR5 expression was noted, although this was not statistically significant. CCR5 and CCR2 mRNA levels were nearly identical for each of the donor PBMC, regardless of genotype. Cell surface CCR5 and CCR2 levels were more variable than mRNA transcript levels, suggesting that an alternative mechanism may influence CCR5 cell surface levels. CCR2-64I is linked to the CCR5 promoter polymorphisms 208G, 303A, 627C, and 676A; however, in transfected promoter reporter constructs, these did not affect transcriptional activity. Taken together, these findings suggest that CCR2-64I does not act by influencing CCR5 transcription or mRNA levels. PMID- 9971831 TI - In vivo and in vitro analysis of baculovirus ie-2 mutants. AB - Upon transient expression in cell culture, the ie-2 gene of Autographa californica nuclear polyhedrosis virus (AcMNPV) displays three functions: trans activation of viral promoters, direct or indirect stimulation of virus origin specific DNA replication, and arrest of the cell cycle. The ability of IE2 to trans stimulate DNA replication and coupled late gene expression is observed in a cell line derived from Spodoptera frugiperda but not in a cell line derived from Trichoplusia ni. This finding suggested that IE-2 may exert cell line-specific or host-specific effects. To examine the role of ie-2 in the context of infection and its possible influence on the host range, we constructed recombinants of AcMNPV containing deletions of different functional regions within ie-2 and characterized them in cell lines and larvae of S. frugiperda and T. ni. The ie-2 mutant viruses exhibited delays in viral DNA synthesis, late gene expression, budded virus production, and occlusion body formation in SF-21 cells but not in TN-5B1-4 cells. In TN-5B1-4 cells, the ie-2 mutants produced more budded virus and fewer occlusion bodies but the infection proceeded without delay. Examination of the effects of ie-2 and the respective mutants on immediate-early viral promoters in transient expression assays revealed striking differences in the relative levels of expression and differences in responses to ie-2 and its mutant forms in different cell lines. In T. ni and S. frugiperda larvae, the infectivities of the occluded form of ie-2 mutant viruses by the normal oral route of infection was 100- and 1,000-fold lower, respectively, than that of wild type AcMNPV. The reduction in oral infectivity was traced to the absence of virions within the occlusion bodies. The infectivity of the budded form of ie-2 mutants by hemocoelic injection was similar to that of wild-type virus in both species. Thus, ie-2 mutants are viable but exhibit cell line-specific effects on temporal regulation of the infection process. Due to its effect on virion occlusion, mutants of IE-2 were essentially noninfectious by the normal route of infection in both species tested. However, since budded viruses exhibited normal infectivity upon hemocoelic injection, we conclude that ie-2 does not affect host range per se. The possibility that IE-2 exerts tissue-specific effects has not been ruled out. PMID- 9971833 TI - Characterization of a membrane calcium pathway induced by rotavirus infection in cultured cells. AB - Some viruses induce changes in membrane permeability during infection. We have shown previously that the porcine strain of rotavirus, OSU, induced an increase in the permeability to Na+, K+, and Ca2+ during replication in MA104 cells. In this work, we have characterized the divalent cation entry pathway by measuring intracellular Ca2+ in fura-2-loaded MA104 and HT29 cells in suspension. The permeability to Ca2+ and other cations was evaluated by the change of the intracellular concentration following an extracellular cation pulse. Rotavirus infection induced an increase in permeability to Ca2+, Ba2+, Sr2+, Mn2+, and Co2+. The rate of cation entry decreased over time as the intracellular concentration increased during the first 20 s. This indicates that regulatory mechanisms, including channel inactivation, are triggered. La3+ did not enter the cell and blocked the entry of the divalent cations in a dose-dependent manner. Metoxyverapamil (D600), a blocker of L-type voltage-gated channels, partially inhibited the entry of Ca2+ in virus-infected MA104 and HT29 cells. The results suggest that rotavirus infection of cultured cells activates a cation channel rather than nonspecific permeation through the plasma membrane. This activation involves the synthesis of viral proteins through mechanisms yet unknown. The increase in intracellular Ca2+ induced by the activation of this channel may be related to the increase in cytoplasmic and endoplasmic reticulum Ca2+ pools required for virus maturation and cell death. PMID- 9971832 TI - A conserved tryptophan-rich motif in the membrane-proximal region of the human immunodeficiency virus type 1 gp41 ectodomain is important for Env-mediated fusion and virus infectivity. AB - Mutations were introduced into the ectodomain of the human immunodeficiency virus type 1 (HIV-1) transmembrane envelope glycoprotein, gp41, within a region immediately adjacent to the membrane-spanning domain. This region, which is predicted to form an alpha-helix, contains highly conserved hydrophobic residues and is unusually rich in tryptophan residues. In addition, this domain overlaps the epitope of a neutralizing monoclonal antibody, 2F5, as well as the sequence corresponding to a peptide, DP-178, shown to potently neutralize virus. Site directed mutagenesis was used to create deletions, substitutions, and insertions centered around a stretch of 17 hydrophobic and uncharged amino acids (residues 666 to 682 of the HXB2 strain of HIV-1) in order to determine the role of this region in the maturation and function of the envelope glycoprotein. Deletion of the entire stretch of 17 amino acids abrogated the ability of the envelope glycoprotein to mediate both cell-cell fusion and virus entry without affecting the normal maturation, transport, or CD4-binding ability of the protein. This phenotype was also demonstrated by substituting alanine residues for three of the five tryptophan residues within this sequence. Smaller deletions, as well as multiple amino acid substitutions, were also found to inhibit but not block cell cell fusion. These results demonstrate the crucial role of a tryptophan-rich motif in gp41 during a post-CD4-binding step of glycoprotein-mediated fusion. The basis for the invariant nature of the tryptophans, however, appears to be at the level of glycoprotein incorporation into virions. Even the substitution of phenylalanine for a single tryptophan residue was sufficient to reduce Env incorporation and drop the efficiency of virus entry approximately 10-fold, despite the fact that the same mutation had no significant effect on syncytium formation. PMID- 9971834 TI - Productive infection of human peripheral blood mononuclear cells by feline immunodeficiency virus: implications for vector development. AB - Feline immunodeficiency virus (FIV) is a lentivirus causing immune suppression and neurological disease in cats. Like primate lentiviruses, FIV utilizes the chemokine receptor CXCR4 for infection. In addition, FIV gene expression has been demonstrated in immortalized human cell lines. To investigate the extent and mechanism by which FIV infected primary and immortalized human cell lines, we compared the infectivity of two FIV strains, V1CSF and Petaluma, after cell-free infection. FIV genome was detected in infected human peripheral blood mononuclear cells (PBMC) and macrophages at 21 and 14 days postinfection, respectively. Flow cytometry analysis of FIV-infected human PBMC indicated that antibodies to FIV p24 recognized 12% of the cells. Antibodies binding the CCR3 chemokine receptor maximally inhibited infection of human PBMC by both FIV strains compared to antibodies to CXCR4 or CCR5. Reverse transcriptase levels increased in FIV infected human PBMC, with detection of viral titers of 10(1.3) to 10(2.1) 50% tissue culture infective doses/10(6) cells depending on the FIV strain examined. Cell death in human PBMC infected with either FIV strain was significantly elevated relative to uninfected control cultures. These findings indicate that FIV can productively infect primary human cell lines and that viral strain specificity should be considered in the development of an FIV vector for gene therapy. PMID- 9971836 TI - Moloney murine leukemia virus infects cells of the developing hair follicle after neonatal subcutaneous inoculation in mice. AB - The nature of Moloney murine leukemia virus (M-MuLV) infection after a subcutaneous (s.c.) inoculation was studied. We have previously shown that an enhancer variant of M-MuLV, Mo+PyF101 M-MuLV, is poorly leukemogenic when used to inoculate mice s.c., but not when inoculated intraperitoneally. This attenuation of leukemogenesis correlated with an inability of Mo+PyF101 M-MuLV to establish infection in the bone marrow of mice at early times postinfection. These results suggested that a cell type(s) is infected in the skin by wild-type but not Mo+PyF101 M-MuLV after s.c. inoculation and that this infection is important for the delivery of infection to the bone marrow, as well as for efficient leukemogenesis. To determine the nature of the cell types infected by M-MuLV and Mo+PyF101 M-MuLV in the skin after a s.c. inoculation, immunohistochemistry with an anti-M-MuLV CA antibody was performed. Cells of developing hair follicles, specifically cells of the outer root sheath (ORS), were extensively infected by M MuLV after s.c. inoculation. The Mo+PyF101 M-MuLV variant also infected cells of the ORS but the level of infection was lower. By Western blot analysis, the level of infection in skin by Mo+PyF101 M-MuLV was approximately 4- to 10-fold less than that of wild-type M-MuLV. Similar results were seen when a mouse keratinocyte line was infected in vitro with both viruses. Cells of the ORS are a primary target of infection in vivo, since a replication defective M-MuLV-based vector expressing beta-galactosidase also infected these cells after a s.c. inoculation. PMID- 9971835 TI - Functional domains of Tat required for efficient human immunodeficiency virus type 1 reverse transcription. AB - Tat expression is required for efficient human immunodeficiency virus type 1 (HIV 1) reverse transcription. In the present study, we generated a series of 293 cell lines that contained a provirus with a tat gene deletion (Deltatat). Cell lines that contained Deltatat and stably transfected vectors containing either wild type tat or a number of tat mutants were obtained so that the abilities of these tat genes to stimulate HIV-1 gene expression and reverse transcription could be compared. tat genes with mutations in the amino terminus did not stimulate either viral gene expression or HIV-1 reverse transcription. In contrast, tat mutants in the activation, core, and basic domains of Tat did not stimulate HIV-1 gene expression but markedly stimulated HIV-1 reverse transcription. No differences in the levels of virion genomic RNA or tRNA3Lys were seen in the HIV-1 Deltatat viruses complemented with either mutant or wild-type tat. Finally, overexpression of the Tat-associated kinases CDK7 and CDK9, which are involved in Tat activation of HIV-1 transcription, was not able to complement the reverse transcription defects associated with the lack of a functional tat gene. These results indicate that the mechanism by which tat modulates HIV-1 reverse transcription is distinct from its ability to activate HIV-1 gene expression. PMID- 9971837 TI - Development of animal models for adeno-associated virus site-specific integration. AB - The adeno-associated virus (AAV) is unique in its ability to target viral DNA integration to a defined region of human chromosome 19 (AAVS1). Since AAVS1 sequences are not conserved in a rodent's genome, no animal model is currently available to study AAV-mediated site-specific integration. We describe here the generation of transgenic rats and mice that carry the AAVS1 3.5-kb DNA fragment. To test the response of the transgenic animals to Rep-mediated targeting, primary cultures of mouse fibroblasts, rat hepatocytes, and fibroblasts were infected with wild-type wt AAV. PCR amplification of the inverted terminal repeat (ITR) AAVS1 junction revealed that the AAV genome integrated into the AAVS1 site in fibroblasts and hepatocytes. Integration in rat fibroblasts was also observed upon transfection of a plasmid containing the rep gene under the control of the p5 and p19 promoters and a dicistronic cassette carrying the green fluorescent protein (GFP) and neomycin (neo) resistance gene between the ITRs of AAV. The localization of the GFP-Neo sequence in the AAVS1 region was determined by Southern blot and FISH analysis. Lastly, AAV genomic DNA integration into the AAVS1 site in vivo was assessed by virus injection into the quadriceps muscle of transgenic rats and mice. Rep-mediated targeting to the AAVS1 site was detected in several injected animals. These results indicate that the transgenic lines are proficient for Rep-mediated targeting. These animals should allow further characterization of the molecular aspects of site-specific integration and testing of the efficacy of targeted integration of AAV recombinant vectors designed for human gene therapy. PMID- 9971838 TI - A role for perforin in downregulating T-cell responses during chronic viral infection. AB - Cytotoxic T cells secrete perforin to kill virus-infected cells. In this study we show that perforin also plays a role in immune regulation. Perforin-deficient (perf -/-) mice chronically infected with lymphocytic choriomeningitis virus (LCMV) contained greater numbers of antiviral T cells compared to persistently infected +/+ mice. The enhanced expansion was seen in both CD4 and CD8 T cells, but the most striking difference was in the numbers of LCMV-specific CD8 T cells present in infected perf -/- mice. Persistent LCMV infection of +/+ mice results in both deletion and anergy of antigen-specific CD8 T cells, and our results show that this peripheral "exhaustion" of activated CD8 T cells occurred less efficiently in perf -/- mice. This excessive accumulation of activated CD8 T cells resulted in immune-mediated damage in persistently infected perf -/- mice; approximately 50% of these mice died within 2 to 4 weeks, and mortality was fully reversed by in vivo depletion of CD8 T cells. This finding highlights an interesting dichotomy between the role of perforin in viral clearance and immunopathology; perforin-deficient CD8 T cells were unable to clear the LCMV infection but were capable of causing immune-mediated damage. Finally, this study shows that perforin also plays a role in regulating T-cell-mediated autoimmunity. Mice that were deficient in both perforin and Fas exhibited a striking acceleration of the spontaneous lymphoproliferative disease seen in Fas-deficient (lpr) mice. Taken together, these results show that the perforin-mediated pathway is involved in downregulating T-cell responses during chronic viral infection and autoimmunity and that perforin and Fas act independently as negative regulators of activated T cells. PMID- 9971839 TI - Group D adenoviruses infect primary central nervous system cells more efficiently than those from group C. AB - Group C adenovirus-mediated gene transfer to central nervous system cells is inefficient. We found that wild-type group D viruses, or recombinant adenovirus type 2 (Ad2) (group C) modified to contain Ad17 (group D) fiber, were more efficient in infecting primary cultures of neurons. Together with studies on primary vascular endothelial cells and tissue culture cell lines, our results indicate that there is not a universally applicable adenovirus serotype for use as a gene transfer vector. PMID- 9971840 TI - Effect of immune priming on Borna disease. AB - Borna disease virus (BDV) is a neurotropic virus with a broad host and geographic range. Lewis rats were immunized against BDV with a recombinant vaccinia virus expressing the BDV nucleoprotein and were later infected with BDV to evaluate protection against Borna disease (BD). Relative to animals that were not immunized, immunized animals had a decreased viral burden after challenge with infectious virus, more marked inflammation, and aggravated clinical disease. These data suggest that a more robust immune response in Borna disease can reduce viral load at the expense of increased morbidity. PMID- 9971841 TI - PrM- and cell-binding domains of the dengue virus E protein. AB - The E-prM proteins of flaviviruses are unusual complexes which play important roles in virus assembly and fusion modulation and in potential immunity-inducing vaccines. Despite their importance, little is known about the biogenesis and structural organization of E-prM complexes. Pulse-chase radiolabeling of dengue virus-infected Vero cells demonstrated a rapid interassociation of E and prM proteins, and sucrose gradient sedimentation analysis suggested that E-prM complexes progressed from simple heteromers to more densely sedimenting structures indicating increased multimerization. E-prM heteromers of even higher complexity were observed in virus particles, suggesting an intracellular assembly process which results in the networking of E-prM subunits into a lattice-like structure found in virus particles. Trypsin cleavage of E-prM-containing virus particles resulted in the release of a soluble 45-kDa fragment of the E protein which retained cell-binding activity. The results suggest that E-prM interactions in dengue virus particles are largely mediated by domains in the carboxy-terminal anchoring domain of E, while cell-binding activity is retained in a trypsin releasable ectodomain of the E protein. PMID- 9971842 TI - Neoplastic transformation-associated stimulation of the in vitro resolution of concatemer junction fragments from minute virus of mice DNA. AB - Minute virus of mice (MVM) shows an oncotropic behavior reflected by its ability to amplify its genome more efficiently in a number of transformed versus normal cells. In vivo and in vitro studies revealed that the major effect of cell transformation on MVM DNA replication occurs at the level of double-stranded replicative-form amplification. In particular, resolution of MVM DNA concatemers into monomers was found to be highly sensitive to neoplastic transformation. PMID- 9971843 TI - Coxsackievirus and adenovirus receptor cytoplasmic and transmembrane domains are not essential for coxsackievirus and adenovirus infection. AB - Coxsackievirus and adenovirus receptor (CAR) from which the cytoplasmic domain had been deleted and glycosylphosphatidylinositol (GPI)-anchored CAR lacking both transmembrane and cytoplasmic domains were both capable of facilitating adenovirus 5-mediated gene delivery and infection by coxsackievirus B3. These results indicate that the CAR extracellular domain is sufficient to permit virus attachment and entry and that the presence of a GPI anchor does not prevent infection. PMID- 9971845 TI - Presidential address: A field of dreams. PMID- 9971846 TI - AAGL inappropriate acts policy. American Academy of Gynecologic Laparoscopists. PMID- 9971844 TI - Resistance of interleukin-1beta-deficient mice to fatal Sindbis virus encephalitis. AB - Interleukin-1beta (IL-1beta) concentrations are frequently elevated in central nervous system (CNS) viral infections, but the pathophysiologic significance of such elevations is not known. To examine the role of IL-1beta in CNS viral pathogenesis, we compared the natural histories of IL-1beta-deficient and wild type 129 SV(ev) mice infected with a neurovirulent viral strain, neuroadapted Sindbis virus (NSV). We found that the incidence of severe paralysis and death was markedly decreased in NSV-infected IL-1beta-/- mice compared to NSV-infected wild-type mice (4 versus 88%, P < 0.001). Despite this marked difference in clinical outcome, no differences in numbers of apoptotic cells or presence of histopathologic lesions in the brains of moribund wild-type mice and those of clinically healthy IL-1beta-/- mice could be detected. These results suggest that IL-1beta deficiency is protective against fatal Sindbis virus infection by a mechanism that does not involve resistance to CNS virus-induced apoptosis or histopathology. PMID- 9971847 TI - Basic neuroanatomy for understanding pelvic pain. PMID- 9971848 TI - Operative management of deep endometriosis infiltrating the uterosacral ligaments. AB - STUDY OBJECTIVE: To describe and assess the efficacy of laparoscopic surgical treatment for patients with pain and deep endometriosis located on the uterosacral ligaments. DESIGN: Retrospective analysis (Canadian Task Force classification II-2). SETTING: University-affiliated hospital. PATIENTS: One hundred ten consecutive women with deep endometriosis infiltrating uterosacral ligaments. INTERVENTION: Operative laparoscopic management of endometriosis. MEASUREMENTS AND MAIN RESULTS: Improvement was reported in 82.3% (70/85) of patients with severe dysmenorrhea and was considered satisfactory in 82.8% (58/70). Improvement also occurred in 88.2% (75/85) of women with deep dyspareunia, and was considered satisfactory in 88.0% (66/75). CONCLUSION: Provided the surgeon is highly skilled in laparoscopy, operative laparoscopy is efficient for the treatment of painful symptoms related to deep endometriosis infiltrating uterosacral ligaments. (J Am Assoc Gynecol Laparosc 6(1):31-37, 1999) PMID- 9971849 TI - Laparoscopic Burch urethropexy in a private clinical practice. AB - STUDY OBJECTIVE: To determine the effectiveness of laparoscopic Burch urethropexy in a private practice setting. DESIGN: Prospective, observational study (Canadian Task Force classification II-2). SETTING: Private practice. PATIENTS: Fifty-one consecutive women with stress urinary incontinence (15 genuine stress urinary incontinence, 36 concomitant degrees of pelvic organ prolapse). INTERVENTION: Laparoscopic Burch urethropexy was performed with sutures in 36 patients and with mesh and staples in 15, in combination with laparoscopic vaginal vault suspension, paravaginal repair, laparoscopic-assisted vaginal hysterectomy, and other procedures. MEASUREMENTS AND MAIN RESULTS: Intraoperative complications occurred in 10% of cases; all were recognized and repaired laparoscopically. Operating time ranged from 55 minutes to 3 hours (median 2 hrs 25 min). Forty four (86%) surgeries were done on an outpatient basis, five women required an overnight stay, and two were admitted. Forty-seven (93%) patients were discharged without a catheter; two had urinary retention requiring a catheter for 5 days. Follow-up ranged from 12 to 42 months (average 24 mo). Forty-eight women (94%) were cured, three (6%) failed therapy, and six (12%) developed de novo detrusor instability. CONCLUSION: Burch urethropexy can be performed safely by laparoscopy in a private practice setting with success similar to that of open technique. Most intraoperative complications can be corrected laparoscopically with no increase in morbidity. (J Am Assoc Gynecol Laparosc 6(1):39-44, 1999) PMID- 9971850 TI - Interim results of the American Vesta trial of endometrial ablation. AB - STUDY OBJECTIVE: To compare results of endometrial ablation using the Vesta system compared with resection and rollerball. DESIGN: Multicenter, prospective, randomized, controlled study (Canadian Task Force classification I). SETTING: Private practice and academic center. PATIENTS: Women with menorrhagia documented by menstrual diaries who failed or refused hormonal therapy and who had no major uterine organic lesions. INTERVENTIONS: Vesta endometrial ablation or traditional endometrial resection and rollerball ablation. MEASUREMENTS AND MAIN RESULTS: Both groups achieved excellent control of menorrhagia. CONCLUSION: Vesta is an attractive alternative to traditional methods of endometrial ablation. (J Am Assoc Gynecol Laparosc 6(1):45-49, 1999) PMID- 9971851 TI - Pain mapping during minilaparoscopy in infertile patients without pathology. AB - STUDY OBJECTIVE: To draw a map of pelvic pain and quantify the level of provoked pain during minilaparoscopy under local anesthesia and conscious sedation. DESIGN: Observational study (Canadian Task Force classification II-2). SETTING: University hospital. PATIENTS: Twenty infertile women. INTERVENTIONS: Minilaparoscopy was performed under local anesthesia and conscious sedation, and cognitive performance was evaluated with the Rey auditory verbal learning task. MEASUREMENTS AND MAIN RESULTS: The diagnostic procedure was performed with one 2 mm micrograsper and one 2-mm microprobe to evaluate the pelvis. In particular we grasped utero-ovarian ligaments; we touched, grasped, and distended fallopian tubes with blue dye; we moved the uterus with a manipulator inserted at the cervix; and we touched and grasped bowel and omentum. Level of pain was recorded on a visual analog scale. Patients had no pathologic findings, including minimal endometriosis and pelvic adhesions. The highest level of pain was recorded when we distended the tubes. No pain was elicited when we touched and grasped ovary, omentum, and bowel. In 10% of women when we stretched the tubo-ovarian ligament we provoked a minimal vagal reaction. CONCLUSION: Minilaparoscopy under conscious sedation for pelvic pain mapping in women without pain or pathology revealed consistently negative findings, validating the value of this measurement. (J Am Assoc Gynecol Laparosc 6(1):51-54, 1999) PMID- 9971852 TI - Follow-up of laparoscopic treatment of stage III-IV endometriosis. AB - STUDY OBJECTIVE: To evaluate the efficacy of conservative laparoscopic surgery in a series of patients with stage III-IV endometriosis. DESIGN: Prospective study (Canadian Task Force classification II-1). SETTING: University-affiliated hospital. PATIENTS: All 141 women who underwent conservative operative laparoscopy for stage III-IV endometriosis between January 1993 and December 1996 and were followed for a minimum of 6 months. INTERVENTIONS: Laparoscopic procedures performed with scissors, bipolar coagulation, and hydrodissection. MEASUREMENTS AND MAIN RESULTS: Clinical examination, transvaginal ultrasonography, and pain questionnaire were scheduled every 6 months postoperatively. The cumulative proportion of pregnant patients and cumulative recurrence rate were calculated by Kaplan-Meier method. Twenty-five women (44%) with infertility became pregnant. Twenty-three (51%) had stage III and two (16.7%, p <0.05) had stage IV endometriosis. The 24-month cumulative pregnancy rate was 57.5%. Thirty-one women (22%) reported pain recurrence during follow-up. Five (3.5%) recurrences were confirmed by histologic examination and eight (5.7%) were documented only by clinical and ultrasonographic findings. No recurrence occurred in the first 6 months of follow-up. CONCLUSION: Operative laparoscopy seems to be effective treatment for stage III endometriosis. A larger series with longer follow-up is necessary to clarify its role in the management of stage IV disease. (J Am Assoc Gynecol Laparosc 6(1):55-58, 1999) PMID- 9971853 TI - Early experience with laparoscopic pelvic lymphadenectomy in women with gynecologic malignancy. AB - STUDY OBJECTIVES: To compare the results of laparoscopic pelvic lymphadenectomy with those of open lymphadenectomy; to assess differences in lymph node yield, operating time, and rate of positive nodes based on experience (early and late); and to evaluate the clinical course of laparoscopic lymphadenectomy. DESIGN: Retrospective case review (Canadian Task Force classification II-2). SETTING: University-affiliated hospital. PATIENTS: Sixty-one women with cervical cancer, one with vaginal cancer, and one with endometrial cancer. INTERVENTIONS: Laparoscopic lymphadenectomy followed by laparotomy or radical vaginal hysterectomy was performed in 19 women between 1994 and 1995, and radical abdominal hysterectomy with pelvic lymphadenectomy was performed in 44 women between 1993 and 1995. MEASUREMENTS AND MAIN RESULTS. Mean lymph node yields at laparoscopic pelvic lymphadenectomy were significantly increased in the group operated during the last 6 months compared with the first 6 months (16.2 +/- 6.8 vs 33.2 +/- 10. 5, p <0.05). After 6 months' experience, lymph node yields were 23.9 +/- 10.3 for laparoscopic lymphadenectomy followed by laparotomy and 23.2 +/ 10.2 for laparoscopic lymphadenectomy followed by radical vaginal hysterectomy (NS). The rate of positive lymph nodes was not significantly different between procedures, 16% and 14%, respectively. Operating time for laparoscopic lymphadenectomy was significantly shorter in the last 6 months (143 +/- 34 vs 78 +/- 18 min, p <0.05). Major complications of the procedure were injury to aberrant obturator and iliac veins in two cases in the early period. Average blood loss was 150 to 350 ml. Two women died due to disease recurrence at minimum of 2.5 years' follow-up; the others were alive without recurrence. CONCLUSION: Laparoscopic pelvic lymphadenectomy was feasible and safe, and did not compromise short-term survival. A learning curve was associated with the procedure, but after a period of learning, pelvic lymphadenectomy can be performed as effectively by laparoscopy as by laparotomy. (J Am Assoc Gynecol Laparosc 6(1):59 63, 1999) PMID- 9971854 TI - Five-year review of endometrial ablation with the SideFire laser fiber. AB - STUDY OBJECTIVE: To determine 5-year results of endometrial ablation with the SideFire laser fiber. DESIGN: All women seen in private office who were candidates for this procedure were followed over 5 years (Canadian Task Force classification II-2). SETTING: Patients were pretreated with depot leuprolide acetate in a private office. All procedures were done in an outpatient surgery center, and no patient was admitted to the hospital. PATIENTS: Eighty-six women with increased bleeding. INTERVENTION: Endometrial ablation with the SideFire laser fiber. MEASUREMENTS AND MAIN RESULTS: After follow-up of 12 to 72 months, 100% of patients had excellent results; 70 (82%) had total amenorrhea. Results were not less satisfactory in younger women. CONCLUSION: The SideFire laser fiber seems to be a good alternative that achieves improved outcomes compared with electrosurgery and balloon devices with hot fluid or electrodes. (J Am Assoc Gynecol Laparosc 6(1):65-69, 1999) PMID- 9971855 TI - Which endometrial polyps should be resected? AB - STUDY OBJECTIVE: To evaluate the efficacy of color Doppler exploration after diagnostic hysteroscopy in choosing which endometrial polyps can be safely left in situ. DESIGN: Prospective, long-term follow-up study (Canadian Task Force classification II-1). SETTING: University hospital. PATIENTS: Two hundred twenty women with hysteroscopically confirmed endometrial polyps. INTERVENTIONS: Transvaginal ultrasonographic surveillance with color Doppler mapping and hysteroscopic resection. MEASUREMENTS AND MAIN RESULTS: We removed 126 (57.2%) polyps because of positive color Doppler map, and 29 (13.1%) with a negative color Doppler map because of symptoms. Sixty-five (29.5%) polyps were not removed because they did not cause symptoms and no Doppler map was found. At follow-up, six were removed because of hemorrhagic episodes. At 3 years, 59 patients with endometrial polyps remained asymptomatic by clinical and ultrasonographic follow up. CONCLUSION: In this series, 59 patients (26.8%) avoided surgical removal of polyps. (J Am Assoc Gynecol Laparosc 6(1):71-74, 1999) PMID- 9971856 TI - Relationship of gynecologic surgery to constipation. AB - STUDY OBJECTIVE: To determine if women undergoing presacral neurectomy, hysterectomy, or other gynecologic surgery experience a greater frequency of constipation than those having no surgery. DESIGN: Concurrent, nonrandomized, retrospective study (Canadian Task Force classification II-2). SETTING: Tertiary medical care center with referral-based practice for the treatment of chronic pelvic pain. PATIENTS: Two hundred fifty-six women forming four groups based on surgical procedure: presacral neurectomy (66), hysterectomy (65), other gynecologic surgery (68), and no surgery (57). INTERVENTIONS: Laparoscopic presacral neurectomies. Other gynecologic surgery included laparoscopy, dilatation and curettage, laparoscopic resection of endometriosis, or any combination of these procedures. MEASUREMENTS AND MAIN RESULTS: Constipation was defined as decrease in frequency of spontaneous bowel movements. A statistically significant greater percentage of patients undergoing surgical procedures were more constipated than those having no surgery: presacral neurectomy, 31.8%; hysterectomy, 27.7%; other gynecologic surgery, 25%; and no gynecologic surgery, 10.5%. CONCLUSION: Pelvic surgery may cause parasympathetic nerve dysfunction leading to constipation. (J Am Assoc Gynecol Laparosc 6(1):75-78, 1999) PMID- 9971857 TI - Reduction of cannula-related laparoscopic complications using a radially expanding access device. AB - STUDY OBJECTIVE: To determine the safety of a new radially expanding access device compared with complication rates associated with sharp laparoscopic cannulas. DESIGN: Prospective, multicenter study (Canadian Task Force classification II-1). SETTING: Free-standing and hospital-based ambulatory surgery centers. PATIENTS: Two hundred twelve women undergoing various laparoscopic procedures and followed over 44 months. INTERVENTION: Five hundred forty-one radially dilating access devices were used exclusively for laparoscopic abdominal wall access. MEASUREMENTS AND MAIN RESULTS: No major vascular injury, abdominal wall bleeding, intestinal injury, bladder or ureteral injury, liver trauma, or postoperative incisional hernia occurred. One patient developed a postoperative mesenteric hematoma probably caused by a venous injury from the Veress needle. Of the 541 radially expanding access cannulas placed, only 6 (1%) slipped, despite absence of fascial anchoring devices. CONCLUSION: Radially dilating abdominal access devices may reduce laparoscopic complications, lessen a surgeon's exposure to liability, and improve patient outcomes while reducing facility costs. (J Am Assoc Gynecol Laparosc 6(1):79-84, 1999) PMID- 9971858 TI - Obstetric history in women with surgically corrected adult urinary incontinence or pelvic organ prolapse. AB - STUDY OBJECTIVE: To compare obstetric histories of women who had surgical correction of urinary incontinence or pelvic organ prolapse with a similar group who did not. DESIGN: Case control study (Canadian Task Force classification II 2). SETTING: Urban, community-based, private practice teaching hospital. PATIENTS: Four hundred eighty women (age 51.4 +/- 13.0 yrs) who underwent corrective surgery for urinary incontinence, pelvic organ prolapse, or both, and whose obstetric history was obtainable through chart review. The control group was composed of 150 women (age 50.7 +/- 9.6 yrs) having routine screening mammography who completed a questionnaire regarding obstetric, gynecologic, and urologic history. MEASUREMENTS AND MAIN RESULTS: Patients and controls did not differ significantly in terms of age, race, height, weight, body mass index, or smoking history. Women who underwent surgery were of greater parity (2.5 +/- 1.2 vs 2.0 +/- 1.2, p <0.001), less often nulliparous (3% vs 18%, p <0.001), less likely to have had a cesarean delivery (4% vs 15%, p <0.001), and more likely to have had a vaginal delivery (94% vs 77%, p <0.001) than those with no surgery. The odds ratio of patients who had a vaginal delivery compared with controls was 4.7 (2.3-8.3), and that for cesarean delivery was 0.22 (0.11-0.43). Analysis of specific delivery information found that, compared with controls, patients were older by 4 years at time of their first delivery (28.9 +/- 4.9 vs 24.9 +/- 4.9 yrs, p <0.001) and more commonly received epidural analgesia intrapartum (87% vs 40%, p = 0.004). Comparisons within the patient group, categorized by indication for surgery, revealed that women who had surgery for either prolapse alone or for both prolapse and incontinence were most likely to have had vaginal deliveries (85% incontinence alone vs 94% prolapse alone vs 97% both, p <0.001). CONCLUSION: Increased parity, vaginal childbirth, maternal age at time of delivery, and use of epidural analgesia are associated with need for operative correction of pelvic organ prolapse or adult urinary incontinence. Conversely, cesarean delivery is associated with less need for surgical correction of incontinence or pelvic organ prolapse. PMID- 9971859 TI - Minilaparoscopy to reduce complications from cannula insertion in patients with previous pelvic or abdominal surgery. AB - STUDY OBJECTIVE: To evaluate the safety and efficacy of minilaparoscopy for visualization and adhesiolysis of intraabdominal adhesions for safe insertion of a primary umbilical cannula in patients who had previous pelvic or abdominal surgery. DESIGN: Prospective, observational study (Canadian Task Force classification II-1). SETTING: University-affiliated hospital. PATIENTS: Twenty women who had previous pelvic or abdominal surgery, excluding tubal ligation and simple appendectomy. INTERVENTION: Minilaparoscopy was carried for visualization and adhesiolysis at the entry site before insertion of an umbilical cannula. MEASUREMENTS AND RESULTS: Eleven patients had Pfannenstiel scars and nine had vertical midline scars from previous surgeries (4 total abdominal hysterectomies, 13 adnexal surgery, 7 cesarean sections, 3 ectopic pregnancies, 1 ruptured appendix, 1 unknown bowel surgery). Thirteen women (65%) had had one previous surgery, five (25%) had had two, and two (10%) had had three. Nine patients (45%) had significant adhesions of omentum or intestine that required adhesiolysis. Mean operating time for minilaparoscopy was 5 minutes for 11 women who had no or minimal adhesions that did not interfere with safe insertion of the umbilical cannula and effective use of a 10-mm telescope, and 25 minutes in 9 patients who required adhesiolysis before insertion of the umbilical cannula because of dense adhesions of omentum or intestine at the entry site. No complications with minilaparoscopy occurred. CONCLUSION: Minilaparoscopy can be performed safely and effectively to reduce serious vascular or visceral injury from insertion of primary cannula in patients who had previous pelvic and/or abdominal surgery. However, conclusions cannot be derived from this study due to the small number of subjects. Further study is necessary in a larger patient population to evaluate efficacy, safety, and advantages of minilaparoscopy over other techniques. (J Am Assoc Gynecol Laparosc 6(1):91-95, 1999) PMID- 9971860 TI - Minilaparoscopic hysterectomy. AB - Minilaparoscopic surgery was performed in a 38-year-old woman scheduled for hysterectomy and ovarian cystectomy. Image resolution was similar to that of conventional laparoscopy. There were no intraoperative or postoperative complications. Since it has many advantages and few complications, minilaparoscopy appears to be an attractive way to decrease morbidity associated with conventional laparoscopy. (J Am Assoc Gynecol Laparosc 5(4):97-100, 1998) PMID- 9971861 TI - Management of injuries to great vessels during laparoscopy. AB - Laparoscopy is useful for diagnosis and treatment of gynecologic pathology. Although techniques and instrumentation have progressed significantly, and physicians have acquired more experience, a great deal of concern remains regarding possible major complications associated with this procedure. (J Am Assoc Gynecol Laparosc 6(1):101-104, 1999) PMID- 9971862 TI - Evidence-based medicine: evaluating diagnostic tests. AB - Physicians have at their disposal a great number of established diagnostic tests, and new ones continue to be developed that are potentially helpful in diagnosing and establishing the prognosis of disease. Many of these tests were either inadequately evaluated or were found, on more careful scrutiny, to be less helpful than first believed. To ensure optimal patient care as well as appropriate use of health care resources, practitioners must be adept in understanding the true efficacy of diagnostic tests that they ask patients to undergo. They must be able to understand the basic language applied in evaluating tests and be able to determine if and when tests are applicable. (J Am Assoc Gynecol Laparosc 6(1):105-112, 1999) PMID- 9971863 TI - Operative hysteroscopy in physiologic distention media. AB - Distention media are essential in operative hysteroscopy to ensure good visualization within the uterine cavity. Carbon dioxide, dextran-70, glycine, sorbitol, mannitol, saline, and Ringer's lactate solution have all been used, but are associated with difficulties that prevent their use with instruments that achieve appropriate current densities. Three new distention media are now available that correct problems associated with the earlier products. (J Am Assoc Gynecol Laparosc 6(1):113-118, 1999) PMID- 9971864 TI - A multicenter, randomized, controlled clinical trial of transfusion requirements in critical care. Transfusion Requirements in Critical Care Investigators, Canadian Critical Care Trials Group. AB - BACKGROUND: To determine whether a restrictive strategy of red-cell transfusion and a liberal strategy produced equivalent results in critically ill patients, we compared the rates of death from all causes at 30 days and the severity of organ dysfunction. METHODS: We enrolled 838 critically ill patients with euvolemia after initial treatment who had hemoglobin concentrations of less than 9.0 g per deciliter within 72 hours after admission to the intensive care unit and randomly assigned 418 patients to a restrictive strategy of transfusion, in which red cells were transfused if the hemoglobin concentration dropped below 7.0 g per deciliter and hemoglobin concentrations were maintained at 7.0 to 9.0 g per deciliter, and 420 patients to a liberal strategy, in which transfusions were given when the hemoglobin concentration fell below 10.0 g per deciliter and hemoglobin concentrations were maintained at 10.0 to 12.0 g per deciliter. RESULTS: Overall, 30-day mortality was similar in the two groups (18.7 percent vs. 23.3 percent, P= 0.11). However, the rates were significantly lower with the restrictive transfusion strategy among patients who were less acutely ill -- those with an Acute Physiology and Chronic Health Evaluation II score of < or =20 (8.7 percent in the restrictive-strategy group and 16.1 percent in the liberal strategy group; P=0.03) -- and among patients who were less than 55 years of age (5.7 percent and 13.0 percent, respectively; P=0.02), but not among patients with clinically significant cardiac disease (20.5 percent and 22.9 percent, respectively; P=0.69). The mortality rate during hospitalization was significantly lower in the restrictive-strategy group (22.3 percent vs. 28.1 percent, P=0.05). CONCLUSIONS: A restrictive strategy of red-cell transfusion is at least as effective as and possibly superior to a liberal transfusion strategy in critically ill patients, with the possible exception of patients with acute myocardial infarction and unstable angina. PMID- 9971865 TI - Lack of effectiveness of bed rest for sciatica. AB - BACKGROUND AND METHODS: Bed rest is widely advocated for sciatica, but its effectiveness has not been established. To study the effectiveness of bed rest in patients with a lumbosacral radicular syndrome of sufficient severity to justify treatment with bed rest for two weeks, we randomly assigned 183 subjects to either bed rest or watchful waiting for this period. The primary outcome measures were the investigator's and patient's global assessments of improvement after 2 and 12 weeks, and the secondary outcome measures were changes in functional status and in pain scores (after 2, 3, and 12 weeks), absenteeism from work, and the need for surgical intervention. Neither the investigators who assessed the outcomes nor those involved in data entry and analysis were aware of the patients' treatment assignments. RESULTS: After two weeks, 64 of the 92 patients in the bed-rest group (70 percent) reported improvement, as compared with 59 of the 91 patients in the control (watchful-waiting) group (65 percent) (adjusted odds ratio for improvement in the bed-rest group, 1.2; 95 percent confidence interval, 0.6 to 2.3). After 12 weeks, 87 percent of the patients in both groups reported improvement. The results of assessments of the intensity of pain, the bothersomeness of symptoms, and functional status revealed no significant differences between the two groups. The extent of absenteeism from work and rates of surgical intervention were similar in the two groups. CONCLUSIONS: Among patients with symptoms and signs of a lumbosacral radicular syndrome, bed rest is not a more effective therapy than watchful waiting. PMID- 9971866 TI - Effects of thyroxine as compared with thyroxine plus triiodothyronine in patients with hypothyroidism. AB - BACKGROUND: Patients with hypothyroidism are usually treated with thyroxine (levothyroxine) only, although both thyroxine and triiodothyronine are secreted by the normal thyroid gland. Whether thyroid secretion of triiodothyronine is physiologically important is unknown. METHODS: We compared the effects of thyroxine alone with those of thyroxine plus triiodothyronine (liothyronine) in 33 patients with hypothyroidism. Each patient was studied for two five-week periods. During one period, the patient received his or her usual dose of thyroxine. During the other, the patient received a regimen in which 50 microg of the usual dose of thyroxine was replaced by 12.5 microg of triiodothyronine. The order in which each patient received the two treatments was randomized. Biochemical, physiologic, and psychological tests were performed at the end of each treatment period. RESULTS: The patients had lower serum free and total thyroxine concentrations and higher serum total triiodothyronine concentrations after treatment with thyroxine plus triiodothyronine than after thyroxine alone, whereas the serum thyrotropin concentrations were similar after both treatments. Among 17 scores on tests of cognitive performance and assessments of mood, 6 were better or closer to normal after treatment with thyroxine plus triiodothyronine. Similarly, among 15 visual-analogue scales used to indicate mood and physical status, the results for 10 were significantly better after treatment with thyroxine plus triiodothyronine. The pulse rate and serum sex hormone-binding globulin concentrations were slightly higher after treatment with thyroxine plus triiodothyronine, but blood pressure, serum lipid concentrations, and the results of neurophysiologic tests were similar after the two treatments. CONCLUSIONS: In patients with hypothyroidism, partial substitution of triiodothyronine for thyroxine may improve mood and neuropsychological function; this finding suggests a specific effect of the triiodothyronine normally secreted by the thyroid gland. PMID- 9971867 TI - Radial scars in benign breast-biopsy specimens and the risk of breast cancer. AB - BACKGROUND: Radial scars are benign breast lesions of uncertain clinical significance. In particular, it is not known whether these lesions alter the risk of breast cancer in women with benign breast disease. We conducted a case-control study of women who had benign breast lesions with or without radial scars. METHODS: We reviewed benign breast-biopsy specimens from 1396 women enrolled in the Nurses' Health Study, including 255 women in whom breast cancer subsequently developed and 1141 women without subsequent breast cancer (controls). The controls were matched to the women with subsequent breast cancer according to age and the year when the benign lesion was identified. The median follow-up after biopsy of the benign lesions was 12 years. RESULTS: Radial scars were identified in biopsy specimens from 99 women (7.1 percent). Most biopsy specimens with radial scars had only one radial scar (60.6 percent), and they tended to be incidental microscopical findings (median size, 4.0 mm). The women with radial scars had a risk of breast cancer that was almost twice the risk of the women without scars, regardless of the histologic type of benign breast disease (relative risk, 1.8; 95 percent confidence interval, 1.1 to 2.9). Among women who had proliferative disease without atypia as compared with women who had nonproliferative disease, the relative risk of breast cancer was 3.0 (95 percent confidence interval, 1.7 to 5.5) for those with radial scars and 1.5 (95 percent confidence interval, 1.1 to 2.1) for those without radial scars. Among women with atypical hyperplasia as compared with women with nonproliferative disease, the relative risk of breast cancer was 5.8 (95 percent confidence interval, 2.7 to 12.7) for those with radial scars and 3.8 (95 percent confidence interval, 2.4 to 5.9) for those without radial scars. CONCLUSIONS: Radial scars are an independent histologic risk factor for breast cancer. PMID- 9971868 TI - Images in clinical medicine. An apoptotic eosinophil. PMID- 9971869 TI - Transfusion medicine. First of two parts--blood transfusion. PMID- 9971870 TI - Acute-phase proteins and other systemic responses to inflammation. PMID- 9971872 TI - Should medical journals try to influence political debates? PMID- 9971873 TI - Transfusions in critically ill patients. PMID- 9971874 TI - Thyroid hormone replacement--one hormone or two? PMID- 9971875 TI - Would cloned humans really be like sheep? PMID- 9971876 TI - The American health care system--the movement for improved quality in health care. PMID- 9971878 TI - Cross-validation and extension of the MMPI-A IMM scale. AB - Seventy-five female and 76 male college undergraduates participated in a cross validation of the IMM scale, developed for the MMPI-A. These participants completed the IMM scale which was scored in two ways: one used the regular MMPI-A score, IMMA, and the other, IMM2, was based on the subset of these items that also appear in the MMPI-2. They also completed a gender-appropriate version of the Washington University Sentence Completion Test (WUSCT) and a brief biographical questionnaire. High inter-rater reliability (.80) was established for scoring the WUSCT for ego developmental level based on the most recent version of the scoring format. Statistically significant correlations were found between ego level scores and both the IMMA and the IMM2 scales. Means and standard deviations on both IMM scales for the males and females in the MMPI-A and the MMPI-2 restandardization samples, respectively, were obtained. PMID- 9971877 TI - Global sequence diversity of BRCA2: analysis of 71 breast cancer families and 95 control individuals of worldwide populations. AB - The aim of this study was to evaluate the prevalence of simple sequence variation in the BRCA2 gene. To this end, 71 breast and breast-ovarian cancer (HBC/HBOC) families along with 95 control individuals from a wide range of ethnicities were analyzed by means of denaturing high-performance liquid chromatography (DHPLC) and direct sequence analysis. In the coding (10 257 bp) and non-coding (2799 bp) sequences of BRCA2, 82 sequence variants were identified. Three different, apparently disease-associated BRCA2 mutations were found in six HBC/HBOC families (8%): two splice site mutations in introns 5 and 21, and one frameshift mutation in exon 11. In the coding region, 53 simple sequence variants were found: 35 missense mutations, one 2 bp deletion (CT) resulting in a stop at codon 3364, one nonsense mutation with a stop at codon 3326, one deletion of a complete codon (AAA) resulting in the loss of leucine, and 15 silent mutations. In the non coding region, 26 polymorphisms were detected. Of the 79 sequence variants that were not obviously disease-associated, eight were detected only in HBC/HBOC families. The remaining 71 variants were identified in both HBC/HBOC families and control individuals. Sixty three sequence variants (80%) were specific for a continent. Forty two percent (33 out of 79) of the sequence variants were detected exclusively in Africa, though only 13% of the 332 chromosomes screened were of African origin. Our data indicate that, in BRCA2, simple sequence variation is frequent [in the coding region 1 in 194 bp (straight theta = 2.2 x 10(-4)), and in the non-coding region 1 in 108 bp (straight theta = 4.4 x 10( 4)), respectively]. PMID- 9971879 TI - Development and validation of a multifactorial treatment outcome measure for eating disorders. AB - The purpose of this investigation was to develop a brief self-report inventory which could be used to evaluate treatment outcome for anorexia and bulimia nervosa. The Multifactorial Assessment of Eating Disorders Symptoms (MAEDS) was constructed to measure six symptom clusters which have been found to be central to the eating disorders: depression, binge eating, purgative behavior, fear of fatness, restrictive eating, and avoidance of forbidden foods. The factor structure of the MAEDS was found to be stable and it was found to have satisfactory reliability and validity. Normative data were collected so that raw scores could be converted to standardized scores. While still in the experimental stages, the MAEDS shows promise as a valid and economical measure of treatment interventions for anorexia and bulimia nervosa. PMID- 9971880 TI - Test-retest reliability of psychological and neurobehavioral tests self administered by computer. AB - A series of 12 psychological and 7 neurobehavioral performance tests were administered twice to a nonclinical normative sample with 1 week between administrations. The tests were presented in a self-administered computerized format. One week test-retest reliabilities were comparable to conventional administration formats. The results suggest that individual test reliability is not affected when tests are administered as part of an extensive multi-measure battery. Computer administered test reliability coefficients also were compared to a Mixed Format (computer-conventional) administration with mixed format reliabilities generally similar to the reliabilities of published conventional tests but also generally lower than same format testing. Compared to psychological test reliability, neurobehavioral test reliability appeared more vulnerable to decreases with mixed format testing. These conclusions should not be generalized to all computer implemented tests as the qualities of the test implementation will affect the outcome. PMID- 9971881 TI - A comparison of nine WAIS-R short forms in individuals with mild to severe traumatic brain injury. AB - Scores from nine WAIS-R short forms were calculated for a sample of 75 adults with mild to severe traumatic brain injury (TBI). Although all nine of the short forms were significantly correlated with the WAIS-R Full Scale IQ, three of the short forms (Vocabulary-Block Design; Vocabulary-Block Design-Arithmetic Similarities; Vocabulary-Arithmetic-Picture Arrangement-Block Design) significantly overestimated the WAIS-R IQ and thus may be inappropriate to use with this population. The remaining six short forms did not differ significantly from the WAIS-R Full Scale IQ. Among these six, Ward s seven-subtest short form appeared to exhibit the least variability in predicting the WAIS-R Full Scale IQ. Information is presented and discussed regarding the absolute difference scores between short form IQ estimates and the WAIS-R as well as the proportion of short forms which significantly under- and overestimate the Full Scale IQ. PMID- 9971882 TI - Factorial validation of the Ruff-Light Trail Learning Test (RULIT). AB - The factorial validity of the Ruff-Light Trail Learning Test (RULIT) was evaluated for its specificity as a test of visuospatial learning and memory. In a sample of 307 normal adults, principal components analyses (PCAs) were calculated on scores from the RULIT and selected neuropsychological tests. The PCAs revealed visuospatial learning and memory components, which included RULIT scores that were empirically distinct from verbal learning and memory components. These results provide support for the RULIT as a measure of visuospatial learning and memory. PMID- 9971883 TI - MMPI-A patterns related to the endorsement of suicidal ideation. AB - This study focused on the relationship between the occurrence of specific Minnesota Multiphasic Personality Inventory Adolescent (MMPI-A) basic scale profile patterns and the frequency of endorsement of three items related, in varying degrees, to suicide ideation (MMPI-A Items 177, 283, and 399). The research sample consisted of adolescents (n = 348) with diagnoses of depression, conduct disorder, and other psychiatric disorders. Significant relationships were found for the overall MMPI-A basic scale profile, several MMPI-A single scale high points, and specific two-point codetype groupings. Findings revealed higher basic clinical scale profiles for those adolescents endorsing suicidal ideation. Further results revealed lower frequencies of item endorsement for spike 4 and spike 9 profiles, and higher item endorsement frequencies for Scale 2, Scale 8, and for the two-point codetypes of 4-8/8-4, 8-9/9-8 and 6-8/8-6. Issues are discussed related to the clinical usefulness and limitations of the MMPI-A in the assessment and prediction of suicidal ideation and behavior in adolescents. PMID- 9971884 TI - The utility of K-correction to adjust for a defensive response set on the MMPI. AB - This study examined the utility of the K-correction procedure to adjust for a defensive response set on the MMPI. The sample consisted of 61 patients with end stage lung disease undergoing psychosocial evaluation for transplantation. Participants were separated into defensive and non-defensive groups using a median split on the K scale (defensive group T score 59) as the cutoff score. The MMPI was scored once in the standard manner and then rescored omitting all K scale items from the clinical scales. As hypothesized, raw score analysis after omitting K-scale items showed the defensive group endorsed significantly fewer items on all five scales involving K-correction (Scales Hs, Pd, Pt, Sc, Ma). Analysis of K-corrected T scores on Scales Hs, Pd, Pt, and Sc using standard procedures showed a significant group difference only on Scale Hs with a higher T score found among the defensive group. The defensive and nondefensive groups were not significantly different in demographic, medical, or psychiatric characteristics suggesting that the tendency to respond in a defensive manner is the major characteristic that distinguishes the two groups. Taken together, these results provide support for the use of the K-correction procedure when examining MMPI clinical profiles among patients with end-stage pulmonary disease undergoing evaluation for transplantation. PMID- 9971885 TI - Ethical perspectives and practice behaviors involving computer-based test interpretation. AB - The debates of the 1980s regarding responsible use of computer-based test interpretation (CBTI) software have mostly disappeared, as CBTI use has become common practice. We surveyed 364 members of the Society for Personality Assessment to determine how they use CBTI software in their work and their perspectives on the ethics of using CBTI in various ways. Psychologists commonly use CBTI software for test scoring and to provide a complementary source of input for case formulations. Most do not use CBTI software as the primary way to formulate a case, nor as an alternative to a written report. Controversy and uncertainty were expressed about importing sections of CBTI narratives into psychological reports. We distinguish between support and replacement functions of CBTI use, arguing that adequate research evidence should be present before using CBTI as a replacement for established assessment procedures. PMID- 9971886 TI - Diagnostic change and personality stability following functional restoration treatment in chronic low back pain patients. AB - This study examined personality pathology in a group of patients with chronic low back pain (CLBP) using both diagnostic interviews and dimensional self-report instruments. A group of CLBP patients (N = 125) was assessed before functional restoration treatment and compared with a matched normal comparison group (N = 75). The CLBP group evidenced broad personality pathology in all assessment modes pretreatment relative to the normal comparison sample. In addition, two subsamples of CLBP patients (n = 49 and n = 56) were assessed after treatment. Reductions in personality pathology between pre- and posttreatment assessments were more pronounced for diagnostic interview than dimensional self-report assessments. These results are discussed in the context of personality assessment and CLBP. PMID- 9971887 TI - Internal consistency of three tests from the Halstead-Reitan neuropsychological battery for older children. AB - The internal consistency of three neuropsychological tests was examined in a sample of 334 referred children (9-14 years of age). Coefficient alpha was calculated to estimate reliability on the Seashore Rhythm Test (SRT), two forms of the Speech Sounds Perception Test (SSPT), and the Aphasia Screening Test (AST). The standard SSPT appears to have relatively good internal consistency with an average coefficient of.81. The average coefficient for the abbreviated form of the SSPT was considerably lower (i.e.,.73), highlighting the superiority of the standard form in clinical practice. Internal consistency of the SRT was relatively low (i.e.,. 67). This level of reliability may be acceptable in group research and for component tests, but is marginal for independent clinical use. Coefficient alpha for the AST was moderate (i.e.,.77), suggesting adequate reliability for a screening test. These reliability estimates are compared to those obtained in previous studies using these tests in adult samples and with other tests commonly used with children. PMID- 9971888 TI - Abstracts of the 30th annual meeting of the british medical ultrasound society, harrogate, 9-11 december 1998 PMID- 9971889 TI - Issues and perspectives on the biocompatibility and immunotoxicity evaluation of implanted controlled release systems. AB - Over the past decade, significant advances and discoveries in cell and molecular biology and biomaterials have provided a foundation for the research and development of new, complex controlled release systems. Many of these new controlled release systems utilize active biological components, i.e., proteins and cells, to achieve their intended therapeutic goal. Utilization of bioactive biological materials in implantable controlled release systems has prompted a broad as well as an in-depth interest in the safety and efficacy of these systems. This short review is intended to provide individuals with a perspective on standards and guidance documents which specifically address biological and immunotoxicity response evaluation for safety of controlled release systems from a regulatory point of view. PMID- 9971890 TI - Incorporation of polymeric nanoparticles into solid dosage forms. AB - Besides parenteral delivery, polymeric nanoparticles have been used for oral drug delivery. In this study, model polymeric nanoparticles (aqueous colloidal polymer dispersions: Eudragit(R) RL 30D, L 30D, NE 30D, or Aquacoat(R)) with different physicochemical properties were incorporated into various solid dosage forms (granules, tablets, pellets or films). The compatibility of the nanoparticles with commonly used tabletting excipients and the redispersibility of the nanoparticles after contact of the solid dosage forms with aqueous media were investigated. Ideally, the nanoparticles should be released from the solid dosage forms with their original properties. The addition of polymeric binders (e.g. polyvinylpyrrolidone, Na carboxymethylcellulose or hydroxypropyl methylcellulose) to the aqueous nanoparticle dispersions prior to wet granulation resulted in phase separation (depletion or bridging flocculation) for many nanoparticle/binder systems. Two critical parameters for the complete redispersibility/release of the nanoparticles with the original particle size properties from the solid dosage forms were a (1) high minimum film formation temperature (MFT) of the polymer dispersion and (2) a good wettability of the dried polymeric nanoparticles. Nanoparticle dispersions with a low MFT were not redispersible, they coalesced into larger agglomerates/films during the drying step. Contact angle measurements correlated well with the redispersibility of the nanoparticles, with ethylcellulose particles having high contact angles and poor redispersibility and Eudragit(R) RL, a polymer stabilized with quaternary ammonium groups, having low contact angles and good redispersibility. PMID- 9971891 TI - Spectrophotometric analysis of molecular transport in gels. AB - An automated spectrophotometric method has been developed for analyzing molecular transport out from and into gels. A Beckman DU7500 diode-array UV-visible spectrophotometer with gel scanner was modified to accept and longitudinally scan a quartz diffusion cell, 0.3x10x40 mm. Molecules of interest are identified and concentrations quantitated via analysis of spectrophotometric absorbance peaks relative to background absorbance of the gel. Thus, concentration profiles are obtained as functions of both position and time. Test data are fitted to a diffusion model via nonlinear least-squares regression. Precision and accuracy of the method were assessed via analysis of several test molecules and gels: (1) 30 mg/ml nonoxynol-9 (N9), contained in 1% sodium alginate gel cross-linked with 2.5 mM calcium chloride, permeating standardized, reconstituted bovine cervical mucus (BCM); (2) 2.5 mg/ml sodium fluorescein, contained in and permeating 10 mg/ml and 100 mg/ml gelatin gels; and (3) 1.0 mg/ml sodium ganciclovir, contained in and permeating 10 mg/ml sodium hyaluronate gel. Diffusion coefficients for (1) and (3) were 3.8x10-7 and 54.1x10-7 cm2/s, respectively. All measurements of diffusion coefficients, partition coefficients, and solute loads obtained in this study were highly repeatable (most C.V.'s<8%). The mean diffusion coefficient for (2) was within 3% of values predicted from theory for the 100 mg/ml gel; the mean partition coefficient for (3) was within 2% of the expected value. This new technique is simpler than many traditional ones in that it does not require labeling of test molecules nor changes in refractive index of target materials. It is particularly well-suited to situations in which the target material is a gel, because no stirring of the target is necessary. PMID- 9971892 TI - Drug release from drug-polyanion complex tablets: poly(acrylamido-2-methyl-1 propanesulfonate sodium -co- methyl methacrylate). AB - A new erodible, anionic carrier for cationic drugs has been synthesized for oral drug delivery systems. The release properties of tablets prepared from this new material, poly(acrylamido-2-methyl-1-propanesulfonate sodium -co- methyl methacrylate) (PAMPSNa/MMA), are discussed. Pseudo-linear release profiles were obtained and the hydrophobicities of both the polymeric carrier and the bound drugs were found to be an important controlling factor in determining the slopes of these release profiles. The effect of the tablet geometry on the shape of the release profiles was also investigated and tablet thickness was demonstrated to be another key parameter controlling both the linearity of the release profiles, as well as the duration of drug release. The release kinetics are strongly dependent on the drug solubility rather than on the type of amine in the drug (i.e. secondary and tertiary amines). The release of drugs from tablets of drug PAMPSNa/MMA complexes were well described by the dissociation/erosion mechanism. PMID- 9971893 TI - Power Doppler imaging in the evaluation of extracranial vertebral artery compression in patients with vertebrobasilar insufficiency. AB - OBJECTIVE: The recent introduction of Power Doppler Imaging (PDI) made a promise for better visualization of blood vessels lying in regions anatomically difficult for ultrasound imaging, i.e. vertebral arteries. The purpose of our study was to assess usefulness of PDI technique in visualization of vertebral artery course and to assess its utility in the detecting spondylotic vertebral artery compression in patients with vertebrobasilar insufficiency (VBI). METHODS: A total of 428 patients with VBI symptoms was evaluated. A total of 282 (66%) patients related their symptoms to a specific head position. Thus, all Doppler examinations were performed in four head positions: hyperextension, flexion and right/left rotation and also in a position reported by a patient to produce symptoms. PDI technique was employed as vertebral artery mapping for precise PW Doppler range gate placing. RESULTS: Vertebral artery compression was found in 73 (17%) patients: 65 unilateral and eight bilateral. The diagnosis was based on flow decrease or its absence shown on PW-Doppler scans, after a specific head turning. CONCLUSION: Vertebral artery compression, related to a specific head position is relatively frequent in patients with VBI symptoms, especially in an older population commonly suffering from cervical spondylosis. PDI facilitates noninvasive Doppler US diagnosis by showing the real course of vertebral artery, particularly its intertransverse portion. PMID- 9971894 TI - Effectiveness of ciprofloxacin microspheres in eradicating bacterial biofilm. AB - The treatment of cultures of planktonic cells and aged biofilm cells of P. aeruginosa and S. aureus with ciprofloxacin (CFX) microspheres of poly(l-lactic acid) (PLA) has been investigated using a modified, open in vitro chemostat system. The kinetics of release of CFX as a function of drug loading and the dose of microspheres were correlated with the rate and extent of killing and eradication of the planktonic cells and biofilm cells cultured on pieces of silicone tubing in the chemostat, respectively. At 71% w/w drug loading, a minimum dose of 7 mg of CFX in microspheres was required to sustain CFX concentration for about 10 h above the minimum inhibitory concentration (MIC) in order to completely eradicate the cells of either bacteria. In contrast, peak concentrations obtained from an equivalent dose of free CFX decreased to low values within 30 min and the bacteria cells were not eradicated. Lower microsphere loadings of CFX were ineffective at the same dose. Thus, this study has identified the formulation requirements for PLA microspheres to sustain CFX concentrations above the MIC for several days in order to eradicate bacteria, particularly aged biofilm cells, in the open chemostat in which the drug is being continually diluted, or similarly at a site of administration, for example, in the peritoneal cavity. PMID- 9971895 TI - Follow-up of Wilms' tumour during pre-operative chemotherapy by qualitative and quantitative sonography. AB - OBJECTIVES: Evaluation of textural changes in Wilms' tumour during chemotherapy by qualitative and quantitative ultrasonography. METHODS: Sonograms of Wilms' tumours during chemotherapy were retrospectively evaluated (N=33) and compared with histopathology. Textural changes were prospectively quantified (N=6) by mean echogenicity (MEAN) and coefficient of variation (CV) of grey levels. RESULTS: Interobserver agreement for volume measurements was strong and for follow-up of sonolucencies moderate. Chemotherapy caused significant volume reduction and two major patterns of change in sonolucencies were observed; either increase or no change. No relationship between sonolucencies and volume changes was present. Sonolucencies yielded an underestimation of necrosis (P<0.001). Trends in MEAN and CV differed between patients. CONCLUSIONS: Volume was the most objective sonographic tumour response parameter. Changes in sonolucencies may provide additional information on tumour response. However, sonolucencies are not an accurate measure of total tumour necrosis. It was not possible to differentiate Wilms' tumour chemotherapy responders from non-responders by MEAN and CV. PMID- 9971896 TI - Cholephilic characteristics of a new cytostatic complex of cisplatin with glycocholate (Bamet-R2). AB - The aim of this work was to investigate both the existence of enterohepatic circulation of cisplatin-cholylglycinate complex, Bamet-R2, and the relevance of biliary versus urinary excretion of this compound. Two experimental models were used: (i) intraluminal perfusion of 'in situ' ileum in anaesthetized rats bearing a biliary catheter that permitted bile sample collection and (ii) conscious rats in which a permanent intraarterial catheter had been implanted to carry out sequential blood sampling after intravenous (i.v.) or intragastric (i.g.) drug administration. Total platinum in serum, bile, ileum, liver, urine and feces was measured by flameless atomic absorption spectroscopy. Serum concentration versus time curves obtained after i.v. administration of 1 micromol Bamet-R2 or cisplatin revealed that the area under the curve was significantly higher for Bamet-R2 than for cisplatin (+48%). Non-ultrafiltrable platinum accounted for 54.8 and 48.4% of serum platinum 168 h after cisplatin and Bamet-R2 i.v. administration, respectively. When the animals received i.g. 1 micromol cisplatin or Bamet-R2, serum concentrations of total platinum were markedly higher (three fold) after Bamet-R2 than after cisplatin administration. The area under the curve was, also in this case, significantly higher for Bamet-R2 than for cisplatin (+28%). This was in part due to the enhanced intestinal absorption of Bamet-R2, as confirmed in experiments on perfused rat ileum, where a markedly higher amount of the drug was found in ileum tissue and bile after perfusion with media containing Bamet-R2 as compared with experiments where cisplatin instead of Bamet-R2 was added to perfusion media. Moreover, after i.v. administration to conscious rats, excretion of Bamet-R2 by the kidney was three-fold lower than that of cisplatin, while elimination of the former compound into feces was four fold higher than that of the latter. In summary, these results indicate that in addition to the previously reported cytostatic activity of Bamet-R2, this complex has interesting cholephilic characteristics typical of bile acids, such as low urinary excretion together with enhanced intestinal absorption and biliary secretion, probably endowed by the cholylglycyl moiety included in the Bamet-R2 molecule. PMID- 9971897 TI - Soft tissue texture analysis by B-mode-ultrasound in the evaluation of impairment in chronic low back pain. AB - OBJECTIVE: Patients complaints in chronic low back pain do not always correspond to the results of X-ray and MRI investigations. The paraspinal muscle is very sensitive to all structural disorders of the spine. We used B-mode-ultrasound to investigate the change of the ultrasonic texture of the paraspinal lumbar muscle in people suffering from low back pain. METHODS: The quantitative texture analysis was defined by the ratio of the mean echo level of a unilateral cross section (L2) of the paraspinal muscle and the level of a central area (L1) of the same cross-section (square 1 x 1 cm, defined by the ultrasonic device). In the lumbar spine there were five cross sections on either side starting at L1 through L5. In the first study healthy males were investigated (n=30). In the second study, 20 males with MRI controlled lumbar disc disorders were investigated. Finally screening was performed with a group of 40 male patients. The last investigation was a pathohistologic cross-check from the ultrasonic findings in five individual shortly after exitus. RESULTS: The ratio showed results >0.6 in the healthy group. The group with lumbar disc disorders showed at the affected levels ratios <0.5. All patients (with one exception) with a lumbar spinal history were detected. Pathohistology confirmed the ultrasonic findings. CONCLUSIONS: The ultrasonic texture analysis of the paraspinal lumbar muscle allows a rapid and easy to perform investigation for relating discal (actually all structural) disorders of the lumbar spine to the reported pain or disability. PMID- 9971898 TI - PLGA nanoparticles prepared by nanoprecipitation: drug loading and release studies of a water soluble drug. AB - The nanoprecipitation technique for preparation of nanoparticles suffers the drawback of poor incorporation of water soluble drugs. The aim of this study was therefore to assess various formulation parameters to enhance the incorporation of a water soluble drug (procaine hydrochloride) into poly(dl-lactide-co glycolide) (PLGA) nanoparticles prepared by this technique. Approaches investigated for drug incorporation efficiency enhancement included the influence of aqueous phase pH, replacement of procaine hydrochloride with procaine dihydrate and the inclusion of excipients: poly(dl-lactide) (PLA) oligomers, poly(methyl methacrylate-co-methacrylic acid) (PMMA-MA) or fatty acids into the formulation. The nanoparticles produced were submicron size (<210 nm) and of low polydispersity. It was found that an aqueous phase pH of 9.3, replacement of procaine hydrochloride with procaine dihydrate and the incorporation of PMMA-MA, lauric and caprylic acid into the formulation could enhance drug incorporation efficiency without the size, morphology and nanoparticle recovery being adversely influenced. For instance changing the aqueous phase pH from 5.8 to 9.3 increased nanoparticle recovery from 65.1 to 93.4%, drug content from 0.3 to 1.3% w/w and drug entrapment from 11.0 to 58.2%. However, the presence of high ratios of lauric acid and procaine dihydrate in the formulation adversely affected the morphology and size of the nanoparticles. Also, PLA oligomers were not considered a feasible approach since it decreased drug entrapment from 11.0 to 8.4% and nanoparticle recovery from 65.1 to 19.6%. Drug release from nanoparticles appears to consist of two components with an initial rapid release followed by a slower exponential stage. This study has demonstrated that formulation variables can be exploited in order to enhance the incorporation of a water soluble drug into PLGA nanoparticles by the nanoprecipitation technique. PMID- 9971899 TI - Ultrasonography in suspected acute appendicitis in childhood-report of 1285 cases. AB - OBJECTIVE: For the assessment of the diagnostic value of real-time ultrasonography (US) in children with suspected acute appendicitis (a.A.) the results of graded compression US are compared with clinical and histological final diagnoses. METHODS: In a prospective study over nearly 9 years we examined 1285 children aged 1-15 years (m=514, f=771). Using a 5-MHz curved array transducer the right lower quadrant was examined in a graded compression technique. RESULTS: Prevalence of histologically proven a.A. was remarkably low (9%). In diagnosis of acute appendicitis in childhood US achieves a sensitivity of 92%, specificity of 98%, a positive predictive value of 90% and a negative predictive value of 98%. The overall accuracy was 98%. Mesenteric lymphadenitis was seen in 181 cases (prevalence 12%) and terminal ileitis occasionally accompanied by mesenteric lymphadenitis was seen in 116 cases (prevalence 9%). CONCLUSION: In children with suspected appendicitis US of the abdomen gives great diagnostical value for differential diagnosis of a.A. and other more frequent inflammatory diseases of the ileocoecal region. Thus US provides further reliable information to the referring physician. Consequently it is necessary to perform US in each child with acute abdominal pain, even if clinical diagnosis seems to be well established. PMID- 9971900 TI - Colour-coded duplex sonography of preocclusive carotid stenoses. AB - OBJECTIVE: The accuracy of colour-coded duplex sonography (CCDS) for differentiating preocclusive stenoses from occlusions of the internal carotid artery (ICA) is a crucial point in non-invasive quantification of atherosclerotic lesions prior to carotid endarterectomy. METHODS: A total of 401 consecutive patients with CCDS followed by ICA arteriographies as gold standard was available for comparison. The entire number was divided into groups of <90%, 90-94%, preocclusive (95-99%) stenoses and occlusions. Sensitivity, specificity, and predictive value for distinguishing these groups were calculated using a contingency table. RESULTS: With CCDS we found a sensitivity of 88% and a specificity of 99% in 43 preocclusive ?95% stenoses. Similar findings were seen in 31 occlusions of the ICA (SE 87%, SP 99%). CCDS accurately differentiates the subgroups of severe carotid obstructions (90-94%, ?95% and occluded) shown by a predictive accuracy of 97, 96 and 93%. Carotid endarterectomies were performed in two of three angiographically occluded but sonographically preocclusive arteries. Intraoperatively preocclusive ICAs were seen in both cases. CONCLUSION: CCDS showed a high accuracy for differentiating preocclusive stenoses and occlusion of the ICA. Intraoperative findings indicated that angiography is not the absolute gold standard for preocclusive carotid disease in every case. Irregularities of the stenosis channel make it impossible to estimate the true area reduction in stenoses ?90%. The hemodynamic estimation of degree of stenosis by Doppler ultrasound may be closer to reality than angiographic measurement. PMID- 9971901 TI - Macromolecular derivatives of N,N-di-(2-chloroethyl)-4-phenylene diamine mustard. 2. In vitro cytotoxicity and in vivo anticancer efficacy. AB - Prodrugs of N,N-di-(2-chloroethyl)-4-phenylene diamine (PDM) based on soluble poly[N5-(2-hydroxyethyl)-l-glutamine] (PHEG) have been evaluated as tumour targeted drugs. These materials are designed to exploit the enhanced permeability of tumour vasculature, combining a passive tumour tropism with systemic liberation of free PDM. Modification of PDM by coupling via oligopeptide spacers onto a polymeric carrier significantly reduced its cytotoxicity towards different cell types in vitro. On the other hand, incubation of the cells with the PHEG-Gly Phe-Ala-Leu-PDM conjugate in the presence of collagenase IV led to the release of lethal amounts of free drug, resulting in higher cytotoxicity for this derivative. The PHEG-Gly-Phe-Ala-Leu-PDM conjugate, which is rapidly degraded by lysosomal and tumour-associated enzymes also showed a decreased systemic toxicity in vivo and could be administered at a dose of 8 mg PDM/kg body weight intravenously, compared with just 2 mg/kg for free PDM. Furthermore, this derivative also showed better antitumour activity against a C26 colorectal carcinoma tumour model, compared with no activity for the free drug. The results indicate that the PHEG-Gly-Phe-Ala-Leu-PDM conjugate is a promising candidate for cancer treatment. PMID- 9971902 TI - Hemodynamic performance of four mechanical bileaflet prosthetic valves in the mitral position: an echocardiographic study. AB - OBJECTIVES: The CarboMedics, Duromedics, Sorin Bicarbon and the St. Jude Medical valves are bileaflet mechanical prostheses of modern but different design. Choosing a valve with the best hemodynamic profile is of clinical importance in patients with small ventricles and a small mitral annulus. METHODS: The hemodynamic performance of these valves in the mitral position was compared in 76 asymptomatic, ambulatory patients with normally functioning prosthesis and left ventricle, using Doppler echocardiography. Of the 76 patients studied, 22 had the CarboMedics, 16 had the Duromedics, 17 had the Sorin Bicarbon and 21 had the St. Jude prosthesis. The patients ages ranged from 18 to 81 years. There were 44 women and 32 men. The time from implantation to echocardiographic study ranged from 1 to 55 months. RESULTS: The echocardiographic study was performed earlier after surgery in the Sorin Bicarbon group. There was no significant difference in women/man ratio, incidence of atrial fibrillation, left ventricular or left atrial diameters between the four groups. The mean prosthesis size was significantly smaller for Sorin Bicarbon and Duromedics valves compared to the CarboMedics and the St. Jude valves (mean+/-SD, 27.2+/-1.3, 27.1+/-1.1 and 30.0+/ 1.9 and 30.0+/-2.7 mm, respectively, P<0.001). Despite its smaller size the Sorin Bicarbon valve had significantly larger effective valve area by Doppler compared to the CarboMedics valve (290+/-40 vs 250+/-60 mm2, respectively, P=0.014). The ratio of effective valve area to prosthesis size was significantly larger for the Sorin Bicarbon valve when compared with any other type of prosthesis. CONCLUSIONS: (1) The Sorin Bicarbon bileaflet valve offered the best hemodynamic results that may be explained by the valve's large leaflet opening angle and small thickness of the leaflets. (2) Since the Sorin Bicarbon is the newest bileaflet valve, durability of this valve remains uncertain. PMID- 9971903 TI - Studies on drug release kinetics from ibuprofen-carbomer hydrophilic matrix tablets: influence of co-excipients on release rate of the drug. AB - Controlled-release (CR) matrix tablets of ibuprofen (IBF) and Carbopol(R) 934P, and blended mixture of Carbopol(R) 934P and 971P resins, at different drug to polymers ratios, were prepared by the direct compression method. The investigation focuses on the influence of the proportion of the matrix material, and several co-excipients (lactose, microcrystalline cellulose (MCC), and starch) on the mechanism and release rate of the drug from the tablets. In vitro drug release in pH 7.2 phosphate buffer solution appears to occur both by diffusion and a swelling-controlled mechanism, exhibiting either anomalous or Case II type transport. The release process could be described by plotting the fraction released versus time and fitting data to the simple exponential model: Mt/Minfinity=ktn. The release kinetics were modified when the blended mixtures of Carbopol(R) 934P and 971P resins were used as the matrix materials. In general, all of the co-excipients, used in this study, enhanced the release rate of IBF. However, lactose demonstrated slower and more linear release behavior as compared to microcrystalline cellulose or starch. The dissolution T50 and T90 values for the three co-excipients were in the order of lactose>microcrystalline cellulose>starch. PMID- 9971904 TI - Percutaneous ethanol injection under general anesthesia for hepatocellular carcinoma: 3 year survival in 112 patients. AB - OBJECTIVE: percutaneous ethanol injection (PEI) under general anesthesia (One Shot PEI) is a new therapy for large and multiple hepatocellular carcinoma (HCC) by the injection of large amount of ethanol in the tumor. We report our results with 3 years survival rates in patients with HCC on cirrhosis treated with One Shot PEI. PATIENTS AND METHODS: between October 1992 and July 1996, 112 cirrhotic patients (79 males; age: 45-80; mean: 64 years) with 215 HCC nodules (diameter 0.6-14 cm; mean 4.1 cm) underwent One Shot PEI. Fifty-three patients had a single nodule (diameter=3-14 cm; mean=4. 5 cm), 59 had two or more (two to five) nodules (diameter=0.6-13 cm; mean=4.9). Ethanol injected ranged between 16 and 120 ml per session. Survival rates were calculated according to Kaplan-Meier method and Wilcoxon test was used for statistical analysis. RESULTS: five patients died within 7 h-10 days after the treatment for rupture of esophageal varices in three cases, rupture of subcapsular HCC in one case and liver failure in one case. In the remaining 107 patients, dynamic CT or spiral CT, performed 72 h-1 month after the treatment, showed complete necrosis in 76 cases (71%) and incomplete necrosis (although always ?50%) in 31. Survival rates at 1, 2, 3 years in all 107 patients were 88, 76, and 76% respectively. Survival rates in Child A Class patients were 100, 92, 92% and in Class B patients were 84, 72, and 72% at 1, 2, 3 years respectively; in Class C were 70 and 40% at 1 and 2 years respectively (P=0.01). Survival rates in patients with single nodule were 95, 82 and 82% at 1, 2 and 3 years, while in patients with multiple nodules were 80, 68 and 58% at 1, 2 and 3 years respectively (P=n.s.). During the follow-up (6-46 months) 48 patients showed intrahepatic recurrences; 41 out of them were retreated with new sessions of One Shot PEI or traditional PEI. CONCLUSIONS: PEI One Shot is more aggressive than traditional PEI. Survival rates of PEI One Shot seems similar to those obtainable by conventional PEI and even better than surgery. PMID- 9971905 TI - The effect of methylated beta-cyclodextrins on the tight junctions of the rat nasal respiratory epithelium: electron microscopic and confocal laser scanning microscopic visualization studies. AB - The nasal absorption enhancer randomly methylated beta-cyclodextrin (RAMEB) is thought to increase the paracellular permeability of the nasal epithelium by opening of the tight junctions. The effects of RAMEB on the cytoskeleton of the rat nasal epithelium in vivo were determined by confocal laser scanning microscopy (CLSM). The effects on the tight junctions of the rat nasal epithelium were also investigated, using transmission electron microscopy (TEM) of thin sections. The effects of RAMEB were compared with those of the absorption enhancer sodium taurodihydrofusidate (STDHF). Fifteen minutes after nasal administration of 2% RAMEB in vivo, the distribution of cytoskeletal actin was comparable to the untreated control, suggesting that RAMEB does not cause opening of the tight junctions via cytoskeletal interactions. In contrast, administration of 1% STDHF resulted in changes in the actin staining. Furthermore, with TEM severe damage of the nasal epithelium was observed after treatment with 1% STDHF. Ultrastructural changes of the tight junctions were not apparent in TEM sections after treatment with 2% RAMEB. In conclusion, CLSM and TEM are suitable methods to visualize the effects of absorption enhancers on nasal epithelial morphology. PMID- 9971906 TI - Sonographic findings of malignant fibrous histiocytoma of the mesentery-report of two cases. AB - We present two cases of malignant fibrous histiocytoma (MFH) of the mesentery. A whorled internal structure observed on sonogram and large feeding and draining vessels demonstrated on color Doppler sonogram in these cases were worth noticing. When sonography reveals an abdominal tumor with such findings, although very rare, the possibility of a MFH of the mesentery must be considered. We also review briefly the literature. PMID- 9971907 TI - An undetected reason for severe fetal growth retardation. AB - In a severely growth-retarded fetus, repeated Doppler ultrasound examinations from the 23rd week of gestation on, showed normal and highly pathological blood flow velocities in the umbilical artery. A caesarean section performed in the 39th week of gestation revealed two true umbilical cord knots. Sonographic screening for umbilical cord knots may be valuable in similar cases. The use of color Doppler could help to visualize the entire course of the umbilical cord. PMID- 9971908 TI - Side-to-side differences of the common carotid artery diameter in presence of asymmetry of the circle of Willis or different vasculopathies. AB - Based on angiographic and carotid ultrasonographic findings in 60 patients with stroke or other diseases, we studied what factors affected the side-to-side differences of the common carotid artery diameter (CCAD). The side-to-side differences of the CCAD were within 0.7 mm in patients with normal cerebral angiogram, but a difference above 0.7 mm was found in many patients with asymmetry of the circle of Willis or different vasculopathies, such as the carotid artery occlusion, cerebral arteriovenous malformation and aortitis. PMID- 9971909 TI - Studies on the interaction of diflunisal ion with cyclodextrins using ion selective electrode potentiometry. AB - The interaction of diflunisal ion (DF) with beta-cyclodextrin (betaCD), gamma cyclodextrin (gammaCD), and hydroxypropyl-beta-cyclodextrin (HPbetaCD) was studied in phosphate buffer, pH 7.4, at 5-37 degrees C and various CD concentrations using a home-made diflunisal ion-selective electrode. Typical direct binding plots and Scatchard plots were obtained with HPbetaCD. The Scatchard model for one class of binding sites was used for the estimation of binding parameters for the DF/HPbetaCD interaction. The estimates for n (number of binding sites per CD molecule) were in all cases very close to unity, indicating 1:1 complexation. The association constant (K) estimates decrease with increasing temperature. Sigmoidal direct binding plots and concave-downwards Scatchard plots were obtained with various betaCD or gammaCD concentrations. The Hill model was used for the estimation of the binding parameters for the DF/betaCD and DF/gammaCD interactions. Both the Hill coefficients and the binding constants were markedly dependent on the CD concentration. These findings indicate the cooperative character of DF/betaCD and DF/gammaCD interactions. The free energy change, DeltaG, and the thermodynamic parameters, DeltaH and DeltaS, were estimated for each of the interactions studied using the Van't Hoff equation. PMID- 9971910 TI - Liposome-skin interactions and their effects on the skin permeation of drugs. AB - The aim of the study was to evaluate the interaction of phospholipid liposomes with skin and stratum corneum lipid liposomes (SCLLs). The influence of phospholipid liposomes on the skin permeability of model drugs was also studied. The transdermal flux of the drugs applied in various phospholipid containing formulations through human epidermis was studied in diffusion chambers. Liposomes in water solutions did not enhance the skin permeability of the drugs, but when ethanol (32% w/v) was present in the donor with EPC (egg yolk lecithin), permeabilities of some model drugs were substantially increased. Confocal microscopy studies revealed that EPC do not penetrate into the skin from water solutions, while from ethanol solutions, EPC penetrates deeply into the stratum corneum. Also, resonance energy transfer between different liposome compositions and the release of calcein from SCLLs showed that interactions between phospholipid liposomes and SCLLs increased with increasing ethanol concentration in the liposome solutions. PMID- 9971911 TI - Influence of neutron irradiation on Eudragit coated tablets: validation of neutron activation II. AB - The in vitro characteristics of enteric coated acetylsalicylic acid tablets and cores were compared before and after irradiation with thermal neutrons, 2, 4, 7 or 15 min at 1.1.1013 neutrons cm-2s-I. The irradiation procedure affected the coated formulation to a greater extent than the cores. Drug release from tablets was already affected after 2 min of exposure, whereas the cores showed no significant inhibition of release until after 15 min of irradiation, leading to the conclusion that the effects of irradiation were caused by a combination of changes both in the core and the coating. Both tablets and cores showed an increase in the disintegration time following irradiation. Scanning electron micrographs (SEM) of non-irradiated cores/tablets and cores/tablets irradiated for 15 min, showed clear differences in the structure of the surface. SEM of the tablets irradiated for 15 min, showed that the irradiation had caused the film to loosen from the core in several places. SEM of the cross-sections of both irradiated tablets and cores showed a partially melted surface above stacked layers with reduced porosity. PMID- 9971912 TI - Influence of the coating thickness and type of oral delivery system (tablets, pellets) on the stability towards degradation by neutron irradiation. Validation of neutron activation III. AB - Enteric coated dexchlorpheniramine maleate (DCPA) tablets and pellets with varying coating thickness were subjected to several in vitro tests after irradiation by thermal neutrons in a flux of 1. 1 x 10(13) n cm-2 s-1 for 2, 4 or 15 min. The appearance of the tablet formulation changed extensively after exposure of the tablets to pile radiation. The irradiation caused the film to loosen from the surface of the core, indicating the generation of gases during the irradiation process. Already after irradiating the tablets for 2 min the disintegration and dissolution behaviour were significantly changed. The extent of tablet damage increased with increasing time of exposure and increasing thickness of the coating. Compared with the tablet formulation, the cores could resist a larger amount of irradiation since dissolution behaviour of the cores was only affected after 15 min of irradiation. This indicates that the irradiation procedure initially affects the coating of the formulation. Although the dissolution behaviour of the pellet formulations changed significantly after the irradiation procedure, the changes were too small to be attributed exclusively to radiation damage. PMID- 9971913 TI - Pharmacokinetic curve fitting using numerical inverse Laplace transformation. AB - The combination of the nonlinear regression program ADAPT II with Talbot's method of numerical Laplace transformation, that allows parameter estimation when the model function is given only in the Laplace domain, is described and successfully applied to pharmacokinetic problems. The accuracy and precision of the method has been found satisfactory; its performance is comparable to that achieved in parameter estimation based on functions defined in the time domain. PMID- 9971914 TI - Bioequivalence evaluation of two omeprazole enteric-coated formulations in humans. AB - Omeprazole, a proton pump inhibitor, effectively suppresses the gastric acid secretion in the parietal cells of the stomach. Several previously published papers focus on the pharmacokinetics of the drug and its interactions with physiological aspects or with other drugs. The increasing number of omeprazole containing products available in the market, raises questions of therapeutic equivalence and/or generic substitution. The bioequivalence evaluation between two or more formulations provides information about in vivo performance. In a favorable decision regarding bioequivalence, the products are considered to have a similar therapeutic efficacy when used under the same therapeutic conditions. This paper reports the design, results and some important aspects involved in a bioequivalence study between two solid oral formulations from different manufacturers. Some important findings were the high intra-subject variability observed for Cmax and the variability observed between subject profiles, probably caused by the multi-unit type of formulations studied. PMID- 9971915 TI - N-terminal 4-imidazolidinone prodrugs of Leu-enkephalin: synthesis, chemical and enzymatic stability studies. AB - Four N-terminal 4-imidazolidinone prodrugs of Leu-enkephalin are prepared and characterized. Their enzymatic and chemical stability are assessed using high performance liquid chromatography. The prodrug derivatives are shown to degrade stoichiometrically to Leu-enkephalin in phosphate buffer [t1/2 (0.05 M phosphate buffer without KCl): acetone prodrug (II) 930 min; cyclopentanone prodrug (III): 216 min; cyclohexanone prodrug (IV): 432 min; 4-methylcyclohexanone prodrug (V): 792 min]. Furthermore, the prodrugs are shown to afford global stabilization of the Leu-enkephalin molecule towards the enzymes, aminopeptidase N and angiotensin converting enzyme, primarily responsible for degradation of Leu-enkephalin at the blood-brain barrier and in plasma. Therefore, the 4-imidazolidinones, being metabolic stable and bioreversible, may be suitable prodrug candidates for delivery of Leu-enkephalin to important target areas such as the brain, if given intravenously. PMID- 9971916 TI - Investigation of the mechanism of flux across human skin in vitro by quantitative structure-permeability relationships. AB - Permeability coefficients for 114 compounds across excised human skin in vitro were taken from Kirchner et al. Forty-seven descriptors were calculated encompassing the relevant physicochemical parameters of the compounds. Quantitative structure-permeability relationships (QSPRs) were developed using least-squares regression analysis. A two-parameter QSPR, describing the permeability coefficients (Kp) across excised skin, was obtained: log Kp=0.772 log P -0.0103 Mr - 2.33 where log P is the logarithm of the octanol-water partition coefficient and Mr is molecular mass. This equation indicates that percutaneous absorption is mediated by the hydrophobicity and the molecular size of the penetrant. Comparison with a QSPR based on penetration across a synthetic (polydimethylsiloxane) membrane suggests that the mechanisms of drug flux across polydimethylsiloxane membranes and excised human skin are significantly different. PMID- 9971917 TI - Physicochemical properties of amorphous clarithromycin obtained by grinding and spray drying. AB - In order to characterize the amorphous clarithromycin (CAM) obtained by grinding and spray drying, physicochemical properties (crystallinity, thermal behavior, stability and solubility parameters) were evaluated. From powder X-ray diffraction, it was estimated that the crystalline state of CAM was changed into an amorphous state by grinding and spray drying. In differential scanning calorimetry measurements, both broad and sharp peaks for crystallization were observed in ground samples, whereas spray dried samples showed one broad peak due to crystallization. As to the stability test under high humidity, structural difference was confirmed between ground CAMs and spray dried CAM. The heat of dissolution of ground CAMs was greater than that of intact CAM. In the solubility parameter measurement, the increase of the special term, deltas, indicated that the energy change was due to the polarity of the surface energy of the powder particles by grinding. PMID- 9971918 TI - Influence of the physico-chemical properties of ophthalmic viscolysers on the weight of drops dispensed from a flexible dropper bottle. AB - The present study investigated the influence of the rheological behaviour, the viscoelasticity and surface tension of various viscolysers on the weight of drops dispensed from a commercially available flexible dropper bottle. Furthermore, the effect of the concentration and molecular weight of some viscolysers and the angle at which the dropper bottle is held, were studied. Up to a value of 25 mPa x s, the viscosity and the rheological behaviour of the solution had no significant influence on the drop weight under conditions simulating patient manipulation. The lower the dynamic surface tension of the solution, however, the lower the weight of drops delivered. The dispensing angle (90 or 45 degrees) of the dropper bottle, on the other hand, had an impact on the weight of drops dispensed. PMID- 9971919 TI - Health care delivery. PMID- 9971920 TI - Effects of mandibular incisor extraction on anterior occlusion in adults with Class III malocclusion and reduced overbite. AB - The aim of this study was to assess the treatment outcome and changes in mandibular incisor position after extraction of one single incisor in 36 adult orthodontic cases with combined Class III and open bite tendencies. The cases consisted of 21 female and 15 male patients with an average age of 27.8 years (standard deviation [SD], 11.1 years) at the start. Fixed 0.018-inch Edgewise appliances were used in both arches in 19 patients and in the mandibular arch in 17 patients. Average treatment time was 18 months (SD, 7.1 months). Pretreatment ANB was 0.5(o) (SD, 2.7 degrees), overjet 1.4 mm (SD, 1.9 mm), and overbite 1.5 mm (SD, 1.1 mm). The lower incisors were 3.6 mm (SD, 2.8 mm) in front of the APg line, and the Averaged Irregularity Index was 1.1 mm (SD, 0.6 mm). Records representing pretreatment (T1), posttreatment (T2), and average 4.3 years (SD, 2.3 years) retention (T3) included cephalograms, panoramic films, intraoral and extraoral photographs, and plaster models. All cast measurements were made with digital calipers. On the cephalograms, the lower incisor tips moved posteriorly 1.7 mm (SD, 2.0 mm) and occlusally 1.5 mm (SD, 1.8 mm) from pretreatment to posttreatment. Relative to the x-axis, they tipped lingually 5.9(o) (SD, 5.6 degrees). On the cast analysis, overjet increased 1.0 mm (SD, 1.9 mm) and 1.5 mm (SD, 1.5 mm) for the maxillary central and lateral incisors, respectively, whereas overbite increased 0.6 mm for both the central and lateral incisors. The intercanine width was reduced by 3.3 mm (SD, 2.0 mm), while the intermolar width was unchanged. The Average Irregularity Index was reduced from 1.1 to 0. 2 mm. Arch-length was reduced 3.6 mm from pretreatment to posttreatment, and another 0.3 mm from posttreatment to 4.3-years retention. Other changes from posttreatment to 4.3-years retention were slight. No loss of the interdental gingival papillae was normally observed. It is concluded that the extraction of one mandibular incisor can lead to satisfactory treatment results in adults with mild Class III malocclusion and reduced overbite, particularly when coupled with a large mandibular intercanine width and minor crowding, and some mandibular tooth size excess. However, the orthodontic treatment frequently became more complicated and time-consuming than expected at the start. PMID- 9971921 TI - A comparison of the shear bond strengths of two glass ionomer cements. AB - The objective of this study was to determine the in vitro shear bond strength (in megapascals) and location of bond failure with two light-cured glass ionomer resin systems. One system was a hybrid glass ionomer cement with resin (GC Orthodontics, Aslip, Ill), and the other system a glass-filled resin system (Reliance Orthodontic Products, Inc, Itasca, Ill). These systems, Fuji Ortho LC (GC Orthodontics) and Ultra Band Lok (Reliance), respectively, were compared to a light-cured composite resin. Maxillary premolar brackets (n = 200) were bonded to the facial surface of human premolar teeth. The two glass ionomer resin systems were each evaluated by two protocols, one according to the manufacturers' direction plus a variation of their respective technique. The five distinct groups (n = 40) were stored in 37 degreesC distilled water for 30 days and subjected to thermocycling before shear bond strength testing. The findings indicated that large variations existed between the bond strengths of the materials tested. The laboratory shear bond strength of the glass-filled resin glass ionomer cement (Reliance), whether tested in a dry or moist field, was similar to the composite control with all of the previous materials being significantly (P <.01) higher than both the hybrid glass ionomer cement groups (Fuji Ortho LC). However, the hybrid glass ionomer cement with enamel conditioner demonstrated a clinically acceptable mean megapascal value. The Adhesive Remnant Index values ranged from 0.53 to 1.62. The hybrid glass ionomer cement without enamel conditioning recorded the lowest mean adhesive remnant index score and the lowest mean megapascal score. Although both products are glass ionomer resin systems, their individual chemistries vary; this affects their clinical performance. Clinically, it may be suggested that glass ionomers used in a dry field may be beneficial for orthodontic bonding, and that glass ionomer resin systems used in a moist environment need an enamel conditioner. PMID- 9971922 TI - Intermaxillary forces during activator treatment. AB - The mode of action of the activator appliance is still unclear. Apart from a possible mandibular growth enhancing effect, some investigators believe that orthopedic forces may be applied to the maxilla, contributing to Class II correction by inhibition of maxillary growth. In addition, orthodontic forces may arise that produce dentoalveolar changes. The purpose of this study was to measure the magnitude of anteroposterior intermaxillary forces during wear of the activator appliance. Ten consecutive patients with Class II dental and skeletal relationships were treated with a modified activator appliance. The appliance had maxillary and mandibular segments that could be detached from each other during the measuring session. A force transducer was placed at the anterior part of the maxillary segment, and the anteroposterior force exerted by the mandibular segment was measured. Measurements were taken in the upright and reclined position at every patient visit for a period of 6 months. Results indicated that intermaxillary forces were generally in the orthodontic range (median values of 100 gf at the upright position and 123 gf at the reclined position). A wide variation in force levels was noted, both between patients and for the same patient during the experimental period. No statistically significant change in force levels was observed during the 6 month period and no difference was noted between upright and reclined posture. PMID- 9971923 TI - Magnetic resonance images and histology of the spheno-occipital synchondrosis in young monkeys (Macaca fuscata). AB - Magnetic resonance images and the histology of spheno-occipital synchondrosis were examined in young monkeys in order to compare the magnetic resonance images with their histologic observations. In serial magnetics resonance images of posterior cranial base, the spheno-occipital synchondrosis showed a low signal zone with unclear boundaries, running through the posterior cranial base perpendicularly to the clivus. The zone was always interposed between nonsignal zones. These observations were the same as those in young juvenile human beings. The histologic sections also revealed that the low signal zone was really the spheno-occipital synchondrosis, which consisted of hyaline cartilage and that the nonsignal zones were bone tissues. The chondroblasts in the spheno-occipital synchondrosis were arranged bipolarly. Intense alkaline phosphatase activity was located in the areas along the bone. Tetracycline labeling was also noticed in the bone formed in the endochondral ossification. These results suggest that magnetic resonance imaging enables us to observe the spheno-occipital synchondrosis in the posterior cranial base and also to elucidate its influences on the growth of maxilla and mandible in the future. PMID- 9971924 TI - Bonding of hybrid ionomers and resin cements to modified orthodontic band materials. AB - Orthodontic bands often fail clinically at the band-cement interface. Hybrid ionomer and resin cements and a glass ionomer control were bonded to photo-etched and standard band materials, both of which were tested in as-received and air abraded conditions. Cements were placed in a 3 mm diameter mold at the bonding interface and bonded to 6 x 6 mm stainless steel band specimens mounted to acrylic blocks. Specimens were stored in water for 24 hours at 37 degreesC and debonded in tension on a testing machine at 0.05 cm/minutes. Bond strengths (MPa) were calculated and data were analyzed by analysis of variance. Bond strengths to as-received bands were less than 3.4 MPa for cements tested, whereas bond strengths to air-abraded bands ranged from 7.1 to 17.7 MPa, except for the glass ionomer control. Air abrasion of band materials provides highly increased bond strength of hybrid ionomer and resin cements. PMID- 9971925 TI - Class II, division 1, case with multiple treatment challenges. AB - This is a case report of a 23-year-old black woman with a skeletal Class II Division 1 malocclusion and an anterior open bite. The maxillary central incisor root was severely dilacerated, a maxillary lateral incisor and canine were transposed, a maxillary canine was impacted near the orbital rim, and a mandibular second premolar was congenitally missing. Selective extractions and attention to detail provided outstanding occlusal function and improved facial esthetics. PMID- 9971926 TI - Analysis of rapid maxillary molar distal movement without patient cooperation. AB - The purpose of this investigation was to evaluate the treatment effects of an intraoral appliance used for rapid distal movement of the maxillary molars. The appliance studied, the Jones jig, is designed to deliver a distalizing force to the maxillary molar against an intraoral anchorage unit thereby eliminating the need for patient compliance. A retrospective study was performed comparing before and after lateral cephalometric radiographs on 13 patients who were treated for an average of 26 weeks with the Jones jig. The cephalometric radiographs were evaluated to determine if there were significant differences between pretreatment and posttreatment variables that included skeletal, dental and soft tissue relationships. Differences between the pretreatment and posttreatment means were significant for mesial angulation of the premolar anchorage unit (P <.001), distal movement of the maxillary molars (P <.01), mesial movement of the premolar anchorage unit (P <. 01), mesial movement of the maxillary incisors (P <.001), and increased lower anterior facial height (P <.01). The anchorage loss, flared maxillary incisors, and increased facial height are negative treatment effects that should be expected when using this or similar appliance design. PMID- 9971927 TI - Impact resistance of ceramic brackets according to ophthalmic lenses standards. AB - The overall resistance to accidental blows of the many ceramic brackets that are sold today has not been explored. Facing a similar diversity, the eyeglasses industry has chosen to standardize the testing of lenses by subjecting them to the drop of a steel ball. By slightly modifying this test, 10 brands of ceramic brackets were examined. In most cases, the findings coincided with those found by other authors when duplicating debonding. Thus, polycrystalline ceramics with bulkier structures and glazed surfaces were found to be more resistant to impact than the monocrystalline brackets, the loftier real "twins," and the less dense attachments. Protruding tie wings and bases were liabilities, and domed configurations seemed to deflect the blows. Bulkier "single" designs alone did not offer a guarantee of impact resistance when not accompanied by an appropriate microstructure and a smooth surface. The ceramic brackets most resistant to impact were found to be 20/20 by American Orthodontics and Fascination by Dentaurum. Medium resistance was displayed by Lumina by Ormco, Allure III and Allure by GAC, Transcend 2000 and Transcend by Unitek/3M; the last was not as good as the other four. The least resistant were Illusion by Ortho-Organizers, Intrigue by Lancer Orthodontics, and Starfire TMB by "A"-Co. Probably because of its real twin design, the last bracket lends itself to the highest probability for accidental breakage. Although resistance to impact and accidental debonding is desirable from the point of view of treatment, the advantage should be weighted against the chance of enamel fracture. Indeed a weak bracket attached with a soft adhesive may be preferable when the chance of an increased exposure to accidental blows is probable. In such cases, the ceramic may take the brunt of the force, instead of the tooth. PMID- 9971928 TI - Skeletal anchorage system for open-bite correction. AB - A skeletal anchorage system was developed for tooth movements. It consists of a titanium miniplate that is temporarily implanted in the maxilla or the mandible as an immobile anchorage. In this article, we introduce the skeletal anchorage system to intrude the lower molars in open-bite malocclusion and evaluate the results of treatment in two severe open-bite cases that underwent orthodontic treatment with the system. Titanium miniplates were fixed at the buccal cortical bone around the apical regions of the lower first and second molars on both the right and left sides. Elastic threads were used as a source of orthodontic force to reduce excessive molar height. The lower molars were intruded about 3 to 5 mm, and open-bite was significantly improved with little if any extrusion of the lower incisors. No serious side-effects were observed during the orthodontic treatment. The system was also very effective for controlling the cant and level of the occlusal plane during orthodontic open-bite correction. PMID- 9971929 TI - Craniofacial adaptations induced by chincup therapy in Class III patients. AB - The purpose of the present study is to examine the effects of an orthopedic force produced by chincup treatment in patients with Class III malocclusion. Anteroposterior maxillary and mandibular changes were examined as were changes in the vertical dimension. Further, the possibility of posterior displacement of temporomandibular joints in treated Class III subjects was evaluated. Serial lateral headfilms of 22 young females (average age, 9 years), who had received chincup therapy were compared with those of 20 skeletal Class III subjects of similar age who received no treatment during the interval studied. A computerized x-y coordinate program was applied to analyze the cephalometric landmarks and measurements. The treated group showed improvement of the skeletal Class III pattern associated with a slight increase (0.8 degrees per year) in SNA and a slight decrease (-0.7 degrees per year) in SNB and also a decreased gonial angle. The distance from the condyle to the chin (Co-Gn or effective mandibular length) increased significantly less in the treated group in comparison with controls. Increases in lower anterior facial height were not different between the treated and untreated groups. In addition, the cranial base angles N-S-Ba and N-S-Ar showed no statistical difference between groups, but these angles tended to increase with time in both groups. Basion and Articulare showed almost the same amount of backward and downward movement in both groups. The results of this study indicate that the primary effect of chincup therapy was in producing a reduction in mandibular growth increments during the period studied. Maxillary growth was not affected during treatment. Further, the results of this study fail to support the hypothesis that chincup appliance significantly induces the posterior displacement of the glenoid fossa. PMID- 9971931 TI - Howard W. Conley. PMID- 9971930 TI - Ethics case analysis: another doctor's mistreatment. Litigation, legislation, and ethics. PMID- 9971932 TI - Erratum: Test of the theory of inelastic breakup for the (3He,d) breakup reaction PMID- 9971933 TI - Erratum: Behavior of pions incident on a slab of uniform complex nuclear material PMID- 9971934 TI - Erratum: Analytic distorted wave approximation for pion scattering from nuclei PMID- 9971936 TI - Erratum: Simple parametrization of the pi -N amplitude PMID- 9971935 TI - Erratum: Uranium target fragmentation by intermediate and high energy 12C and 20Ne ions PMID- 9971937 TI - Erratum: Angular distributions in heavy-ion-induced fission PMID- 9971938 TI - Erratum: Elimination of the linear energy dependence of nonlocal optical potentials PMID- 9971939 TI - Erratum: Identification of collective flow by transverse-momentum analysis of emulsion data for Au+AgBr and Xe+AgBr PMID- 9971940 TI - Erratum: Comparison of SU(3) phenomenologies in the sd shell PMID- 9971941 TI - Erratum: "Exact" relativistic theory of two-body bound-state wave functions PMID- 9971942 TI - Erratum: Effects of center-of-mass motion in the resonating-group theory of n PMID- 9971943 TI - Erratum: Relativistic quarks in one-dimensional periodic structures PMID- 9971944 TI - Erratum: 6Li--> alpha PMID- 9971945 TI - Erratum: Elastic electromagnetic form factors of 6Li from three-body models PMID- 9971947 TI - Erratum: Preequilibrium neutron emission in the reactions 90Zr, 208Pb(p,xn) with 80 MeV projectiles PMID- 9971946 TI - Erratum: Total cross section and resonance spectroscopy for n+86Kr PMID- 9971948 TI - Erratum: Some general properties of the O( alpha ) corrections to parity violation in atoms PMID- 9971949 TI - Erratum: Testing the standard model by precise determinations of W* and Z masses PMID- 9971950 TI - Erratum: Stability of charged rotating black holes in the eikonal approximation PMID- 9971951 TI - Erratum: Onsager principle of microscopic reversibility and supersymmetry PMID- 9971952 TI - Erratum: Ultralight Dirac neutrinos from possible supergrand scenario PMID- 9971954 TI - Erratum: K+13 decays involving finite neutrino mass and mass mixing PMID- 9971953 TI - Erratum: Time variation of coupling constants in Kaluza-Klein cosmologies PMID- 9971955 TI - Erratum: Glueball theory of the xi (2.22) PMID- 9971956 TI - Erratum: Gauge invariance and the finite-element solution of the Schwinger model PMID- 9971957 TI - Erratum: Majorana neutrinos and photinos from kaon decay PMID- 9971958 TI - Erratum: Production and detection of high-energy neutrinos from Cygnus X-3 PMID- 9971959 TI - Erratum: Asymptotic scaling in Hamiltonian calculations of the O(3) sigma model PMID- 9971960 TI - Erratum: Nonrelativistic potential scattering through the shifted large-dimension expansion PMID- 9971961 TI - Erratum: Comparing the Schrodinger and spinless Salpeter equations for heavy quark bound states PMID- 9971962 TI - Erratum: Evolution of cosmic strings PMID- 9971963 TI - Erratum: Feynman path integral and the photon PMID- 9971964 TI - Erratum: Wess-Zumino action from the Grammer-Yennie approximation PMID- 9971965 TI - Erratum: Temperature-induced interaction: lambda phi4 theory PMID- 9971966 TI - Erratum: Evolution of evaporating black holes in an inflationary universe PMID- 9971967 TI - Erratum: Evolution of cosmic strings PMID- 9971968 TI - Erratum: Quantum gauge fields at high curvature PMID- 9971969 TI - Erratum: Relics of cosmic quark condensation PMID- 9971970 TI - Erratum: How to measure the curvature of space-time PMID- 9971971 TI - Erratum: Meson-exchange models for low-energy nucleon-antinucleon scattering PMID- 9971973 TI - Erratum: Electroweak production of heavy quarks in e+e- annihilation PMID- 9971972 TI - Erratum: Analytic bounds on all light-Higgs-boson masses from supergravity PMID- 9971975 TI - Erratum: Detecting the radiation amplitude zero in e+/-p-->e+/-p gamma PMID- 9971974 TI - Erratum: Non-Abelian symmetries from higher dimensions in string theories PMID- 9971977 TI - Erratum: Penguin matrix elements in chiral perturbation theory and in vacuum insertion PMID- 9971976 TI - Erratum: Analysis of charm-->PP based on SU(3) symmetry and final-state interactions PMID- 9971978 TI - Erratum: B0-->D0+ gamma decay as a probe for short-distance QCD corrections PMID- 9971980 TI - Erratum: Analytic expression for baryon semileptonic decay rate PMID- 9971979 TI - Erratum: From QCD to the low-energy effective action through composite fields: Goldstone's theorem and f pi PMID- 9971981 TI - Erratum: Null-plane formulation of Bethe-Salpeter qqq dynamics: Baryon mass spectra PMID- 9971982 TI - Erratum: Approximate higher-order corrections and changes of scales in large-pT physics PMID- 9971984 TI - Erratum: Equation of motion for bubble boundaries PMID- 9971983 TI - Erratum: Strategies to search for the standard-model Higgs boson at a 1-TeV e+e- collider PMID- 9971985 TI - Erratum: Exponentiation of soft photons in Monte Carlo event generators: The case of the Bonneau-Martin cross section PMID- 9971986 TI - Erratum: Nonmonotonic behavior of a contact angle on approaching critical end points PMID- 9971987 TI - Erratum: Experimental study of the signal-to-noise ratio of stochastic resonance systems PMID- 9971988 TI - Erratum: Manifolds in random media: Multifractal behavior PMID- 9971989 TI - Erratum: Fluctuations in solidification PMID- 9971990 TI - Erratum: Measurement of the persistence length of polymerized actin using fluorescence microscopy PMID- 9971991 TI - Erratum: Strongly localized gap solitons in diatomic lattices PMID- 9971992 TI - Erratum: Metastable wetting layers PMID- 9971993 TI - Erratum: Soliton growth-signal transduction in topologically quantized T cells PMID- 9971994 TI - Erratum: Phase transitions in solutions of variably ionizable particles PMID- 9971995 TI - Erratum: Multilevel tunneling and coherence: Dissipative spin-hopping dynamics at finite temperatures PMID- 9971996 TI - Erratum: Deformation and adhesion of elastic bodies in contact PMID- 9971997 TI - Erratum: Escape from a fluctuating double well PMID- 9971998 TI - Erratum: alpha -particle transport-driven current in tokamaks PMID- 9971999 TI - Erratum: Phase diagram and critical behavior of the ferromagnetic Heisenberg fluid from density-functional theory PMID- 9972000 TI - Erratum: Stationary probability distribution near stable limit cycles far from Hopf bifurcation points PMID- 9972001 TI - Erratum: Classical stochasticity threshold and quantum mechanics PMID- 9972002 TI - Erratum: Kinetic theory of multicomponent dense mixtures of slightly inelastic spherical particles PMID- 9972004 TI - Erratum: Growth of breakdown susceptibility in random composites and the stick slip model of earthquakes: Prediction of dielectric breakdown and other catastrophes PMID- 9972003 TI - Erratum: Folding RNA with the minimal loss of entropy PMID- 9972005 TI - Erratum: Non-Poisson statistics of reactive events and nonexponential kinetics PMID- 9972006 TI - Erratum: State diagram of polydisperse elastic-disk systems PMID- 9972007 TI - Erratum: Zipf's law in percolation PMID- 9972008 TI - Erratum: Hydrodynamic interaction of particles with grafted polymer brushes and applications to rheology of colloidal dispersions PMID- 9972009 TI - Erratum: beta +-electron-capture decay of 69Se PMID- 9972010 TI - Erratum: Differences in straggling for positrons and electrons PMID- 9972011 TI - Erratum: Spin density and the real part of the heavy-ion potential PMID- 9972012 TI - Erratum: Approximate energy correction for particle number symmetry breaking in constrained Hartree-Fock plus BCS calculations PMID- 9972013 TI - Erratum: Quadrupole moments and band-mixing in tungsten nuclei PMID- 9972014 TI - Erratum: "Determination of energies and widths of neutron-unbound states from heavy-ion collisions" PMID- 9972015 TI - Erratum: Unusual behavior of projectile fragments produced by the interactions of relativistic Ar ions with copper PMID- 9972016 TI - Erratum: Radioactivity in strange quark matter PMID- 9972018 TI - Erratum: Charge dependence and electric quadrupole effects on single-nucleon removal in relativistic and intermediate energy nuclear collisions PMID- 9972017 TI - Erratum: Microscopic calculation for Ne on NaF at 45 MeV per nucleon PMID- 9972019 TI - Erratum: Particle multiplicity dependence of high-energy photon production in a heavy-ion reaction PMID- 9972020 TI - Erratum: Search for particle-bound neutral nuclei in heavy-ion-induced reactions PMID- 9972022 TI - Erratum: Parametrization of thermal photon emission rates from mesonic matter PMID- 9972021 TI - Erratum: Inelastic scattering of polarized protons from 4He at 500 and 800 MeV PMID- 9972023 TI - Erratum: Inertial parameters of the Skyrmion-Skyrmion system with the product ansatz PMID- 9972025 TI - Erratum: Theoretical description of octupole correlations in the 138-148Xe nuclei PMID- 9972024 TI - Erratum: Complex, energy-independent, local potential reproducing an absorptive phase shift and a bound state PMID- 9972026 TI - Erratum: From nuclear matter to finite nuclei. I. Parametrization of the Dirac Brueckner G matrix PMID- 9972027 TI - Erratum: Exchange process amplitudes in coherent pion production PMID- 9972029 TI - Erratum: Kaon-nucleon couplings for weak decays of hypernuclei PMID- 9972028 TI - Erratum: Baryon-baryon components in the deuteron as quark-exchange currents PMID- 9972030 TI - [Health surveys in the school environment: between rigor and opportunity]. PMID- 9972031 TI - [The consumption of tobacco, alcohol and noninstitutionalized-use drugs by middle school students of Terrassa]. AB - BACKGROUND: Because adolescence is the stage during which most people begin their drug use, we wanted to investigate adolescent's use of and attitudes towards drugs. This paper aims to describe prevalence of students (14-18 years old) drug use in the city of Terrassa (Spain) for the school year 1994-1995. METHODS: A school survey was carried out for a representative sample of 1,269 students. A questionnaire was developed following W.H.O. guidelines. It includes information on demographic characteristics, legal and illegal drug use, information and attitudes towards drugs, and other related factors. RESULTS: Thirty seven percent smoked within the last 30 days, and 60% drunk alcohol. Thirty-two percent had been drunk at least once. Cannabis was the most widely used drug (25.9%) followed by hallucinogens (7.2%), tranquillizers (4.4%), inhalants (4.3%), amphetamines (4%), cocaine (1.7%) and heroin (0.2%). The prevalence for the use of cannabis within the last 30 days was 11%, and around 1% for the use of all other drugs within the same period of time. Increased drug use was observed with age. No differences among sexes were observed for prevalence of tobacco and alcohol use, although boys showed a more intensive pattern. For the other drugs, higher prevalence was observed in the male population except for tranquillizers whose use was more prevalent among women. CONCLUSIONS: The high prevalence of drug use observed, suggest the need to introduce more extensively programs for the prevention of drug use, beginning in primary school. PMID- 9972032 TI - [Tobacco consumption among the student population. Related factors]. AB - OBJECTIVE: To know smoking prevalence among schoolchildren and factors related with this habit. METHODS: A cross-sectional study. 548 school-children in their 6th and 8th years of primary studies at schools from an area of Cordoba (Spain) were interviewed. INTERVENTIONS: Autoadministered questionnaire. RESULTS: Tobacco was tried in 22% (CI 95%: 18.7-25.8) school-children. The average age for starting with this habit was 11.6 (SD)(CI 95%: 11.4-11.8). 12.1% smoked regularly and 1.3% smokers every day. The tobacco consumption in children was related with age (OR = 2.96; CI 95%: 1.12-7.82), cough medicines consumption (OR = 3.15; CI 95%: 1.32-7.48), to have a smokers sister (OR = 2.53; CI 95%: 1.06-6.00) and best friend (OR = 4.42; CI 95%: 1.85-10.60) and drinking beer (OR = 3.68; CI 95%: 1.15 11.7). CONCLUSIONS: The prevalence of smoking in our school-children is very close to that reported by others. Among the factors accounted with the tobacco consumption in schoolchildren, highlight the presence of this habit in the eldest sister and the best friend. PMID- 9972033 TI - [The relationship between personality, attitudes and alcohol and tobacco consumption and exercise in students]. AB - OBJECTIVE: To study the relation between tobacco and alcohol use and exercise, attitudes toward these habits, and the Sensation-Seeking personality trait in students. SUBJECTS AND METHODS: A transversal descriptive study was carried out in the city of Lerida in 1990 in a sample of 430 sixth-grade students and 383 eighth-grade students. The sample was obtained by random sampling of aggregates and stratified by the titularity of the school. An analysis was made of the tobacco and the alcohol use, the levels of physical exercise and the attitudes, among other variables, using the FRISC questionnaire. In eighth grade students, the Sensation-Seeking personality questionnaire was added. RESULTS: The overall scores for Emotion Seeking (EMS), Disinhibition (DIS), Sincerity, and the overall score for Sensation Seeking (SS) were higher for males. The students most active in sports had more favorable attitudes toward exercise and higher EMS and DIS scores. Smokers and drinkers had favorable attitudes toward these habits, opposed their prohibition, and had higher scores for all the subscales and the overall SS. There was a correlation between favorable attitudes toward tobacco (-0.38) and alcohol (-0.51), and the DIS score. Attitudes toward alcohol also correlated with the overall SS score. DISCUSSION: There was a close relation between habits, attitudes, and personality. Although the approach for modifying unhealthy habits should be proposed from a multifactorial perspective, the SS questionnaire could be a useful element for detecting persons who feel the need to seek new sensations and refocusing this tendency on healthier habits. PMID- 9972034 TI - [The consumption of tobacco, alcohol and other drugs by adolescent Spanish students]. AB - OBJECTIVES: This study was undertaken in the mid-1990s (1994) to describe the use of tobacco, alcohol, and non-institutionalized drugs among pre-adolescent and adolescent Spanish students. METHODS: Information was collected within the framework of a periodic transversal study of life styles among European students, with particular emphasis on health-related habits. In the current study we present the results of the last survey carried out in Spain within the context of this study (1994), which involved a representative sample of Spanish students 11, 13, 15, 17 and 18 years-old (n = 6,711). An anonymous questionnaire was completed by the students in class. The survey sampling uses proportionate stratification and multistage sampling. RESULTS: In 1994, 49% of the Spanish students in this age group had tried tobacco. Twenty-four percent were sporadic or regular smokers. There was a large proportion of female smokers than male smokers (27% vs 20%). The overall proportion of smokers increased from 3% at 11 years to 47% at 18 years. One third (33%) of the 18-year-old students smoked daily. Eighty-four percent of the students of this age indicated that they had tried one or more types of alcoholic beverage. Twenty-one percent consumed alcohol regularly (at least once a week). Regular alcohol use was somewhat more common among males (24%) than among females (19%). Forty-six percent of the 18-year-old students consumed alcoholic beverages regularly and 66% had been intoxicated one or more times. Almost one fifth (18%) of the 13-to-18 year-old students indicated that they had tried some type of non-institutionalized drug, although the current rate of consumption was 8%. Cannabis was the drug most frequently tried (18%) and the drug most often consumed at present (8%), followed by cocaine and heroin. More males than females had tried non-institutionalized drugs. DISCUSSION: Analysis of the data revealed that adolescent tobacco use is increasingly frequent among females. Alcohol use continues to be widespread among Spanish pre-adolescents and adolescents. Alcohol use begins in childhood and becomes consolidated in adolescence. The results suggest, in relation to gender differences in the use of tobacco, alcohol, and non-institutionalized drugs, that there is a strong tendency toward the homogenization of these habits between genders. It is necessary to emphasize the preventive measures of drug dependence among Spanish pre-adolescents and adolescents. PMID- 9972035 TI - [Health-related behaviors in secondary-school students: sexual relations and tobacco, alcohol and cannabis consumption]. AB - BACKGROUND AND OBJECTIVES: The main premature mortality causes among youngsters are related to risk behaviors, usually initiated in adolescence. The study objective is to describe substance use and sexual behaviours among 10th-grade Barcelona students in 1996 (last year of compulsory education), as well as the interrelations between these variables and several sociodemographic variables. METHODS: Cross sectional study. Random sample including 35 10th grade classrooms (958 students whose mean age is 15.8 years old) stratified by academic or vocational studies, public or private school, school neighbourhood socioeconomical level and school size. Measurement instrument is a previously validated questionnaire. Tobacco, alcohol, and cannabis consumption, sexual intercourse as well as gender, age, weekly available money, parental instruction and type of studies are studied. Bivariate chi 2 analysis and multivariate gender specific log-linear model are performed. RESULTS: 27% of the students smoke daily and 31% drink alcohol weekly. 15% have had sexual intercourse, and among those 79% use always or almost always condoms. Among girls tobacco consumption is related to alcohol (OR = 4.2), to cannabis (OR = 5.9) and sexual intercourse (OR = 3.9), and, less strongly, with age, available money and vocational studies. Alcohol is associated with tobacco and cannabis use (OR = 4.2). Having had sexual intercourse is related to tobacco use, age (OR = 3.4), vocational studies (OR = 2.4) and cannabis experience (OR = 2.8). Among boys tobacco consumption is related to alcohol, (OR = 2.7), to cannabis (OR = 7.6) and sexual intercourse (OR = 4.4), and, less strongly, to available money and type of studies. Alcohol consumption is associated with tobacco and cannabis use (OR = 5.5). Sexual intercourse is related to tobacco use and age (OR = 2.5). DISCUSSION: Risk behaviors among final year secondary school students are strongly and significantly interrelated, both among boys and among girls, and are more frequent among older students, those with more money available and those in vocational curricula. PMID- 9972036 TI - [A criterion for omitting superfluous variables in regression models]. PMID- 9972037 TI - [Changes in the lymphoma incidence in the population of Tarragona 1984-1992]. PMID- 9972038 TI - [Medline. The Internet versus CD-Rom]. PMID- 9972040 TI - Similarities and interactions between GABAergic and glutaminergic systems. AB - Harmonious interactions between neurotransmitter systems are important for regulating the activity in the central nervous system (CNS). gamma-Aminobutyric acid (GABA) and glutamate (Glu) are major inhibitory and excitatory neurotransmitters in the mammalian central nervous system. Neuronal excitability, probably synaptic plasticity, cognitive performance, learning and memory processes frequently the results of the balance of GABAergic inhibitory and glutaminergic excitatory inputs. PMID- 9972041 TI - Histological diagnosis of gastritis based on Sydney System. AB - The review of literature concerning gastritis, especially the chronic form has been carried out. Based on published data and own authors experience an application of the Sydney System in differential diagnosis of gastritis was presented. PMID- 9972042 TI - Cellular serine carboxypeptidases. AB - The literature on serine carboxypeptidases of cells is reviewed. These proteases occur in the vacuoles of fungi and higher plants and in the lysosomes of animals and man cells. Physico-chemical properties, chemical structure, catalytic mechanism and substrate specificity of these enzymes are presented. PMID- 9972043 TI - The effect of cyclophosphamide on the ultrastructure of erythrocytes. AB - The aim of the present study was to analyse the effect of single intraperitoneal administration of cyclophosphamide (150 mg/kg b.w.) on the morphological changes in erythrocytes. The study of erythrocytes was based on the ultrastructural analysis in the transmission electron microscope (TEM)--in situ examinations and ultrastructural analysis in the scanning electron microscope (SEM)--in vitro examinations of the blood collected from the right and left ventricle of the heart. A single intraperitoneal cyclophosphamide administration was found to cause in the deformability of erythrocytes, which was observed both in TEM and SEM. The altered shape of erythrocytes observed in SEM referred mainly to the blood samples collected from the left ventricle rather than the right. The results obtained suggest that the changes in erythrocyte deformability may cause the development of pulmonary microembolism observed after intraperitoneal administration of cyclophosphamide. PMID- 9972044 TI - Hyphomycetes in rain water draining from intact trees. AB - The authors investigated Hyphomycetes in rain water flowing down from leaves of 10 gymnospermous and 10 angiospermous tree species in northeastern Poland. The presence of 57 Hyphomycetes species was noted. Only 17 species were found to develop both on gymnospermous and angiospermous tree species out of 57 found in rain water flowing down the trees. 16 Hyphomycetes species were observed in rain water flowing down the angiospermous trees, while 24 species in the water from the gymnospermous trees. 13 Hyphomycetes species were recorded for the first time from Poland. PMID- 9972045 TI - Hyphomycetes in the snow from gymnosperm trees. AB - The presence of 26 hyphomycete species was noted in snow water collected from coniferous trees. Camposporium pellucidum, Monodictys peruviana, Polystratorictus fusarioideus, Sporidesmium moniliforme, Tripospermum acerinum and Veronaea botryosa were recorded for the first time to Poland. Among the 26 species found in snow water from coniferous trees predominance of the socalled aero-aquatic hyphomycetes and only a few species belong to the group of aquatic hyphomycetes. PMID- 9972046 TI - Effects of Venoruton on early postradiation damage in the lungs of rats. AB - The study aimed at testing the effects of Venoruton on the early postradiation damage in the lungs of rats. The chests of the rats were irradiated with Co-60, fractional dose 250 cGy/DD, total dose 2500 cGy/DD. Venoruton was given intraperitoneally, in quantities of 0.1 ml once daily for 90 days. The experiment have proved that Venoruton lowers the intensity of the early postradiation changes, mainly those which depend on the vascular damage. PMID- 9972047 TI - Estimation of platelet function state in the course of trichinella spiralis infection. AB - Platelets are part of body defence system, especially the antiparasite immunologic response. Platelets manifest their functions only after their activation. Thrombin activates platelets inducing change of their shape and causing secretion of certain substances. This study was designed to estimate blood platelets morphology as an indicator of their activation and effectiveness of antiparasite therapy. The study was conducted in group of 21 patients infected with T.spiralis before treatment (T1) and group of 19 patients after two weeks of treatment (T2). The diagnosis of trichinellosis was established on the bases of epidemiologic history, clinical picture and immunologic investigations. In the course of trichinellosis and after antiparasitic treatment increase of blood platelet count was observed. The decreased mean platelets volume observed in trichinellosis may be connected with their activation and releasing platelet factor 4 and beta-thromboglobulin. We suggest that T.spiralis activates platelets and the degree of their activation determines their morphologic parameters. PMID- 9972048 TI - The liver ultrastructure in caerulein and taurocholate acute pancreatitis in the rats. AB - The purpose of the study was to compare the morphological alterations of the liver in two models of acute pancreatitis: caerulein-induced (edematous) and taurocholate-induced (necro haemorrhagic one). The experiments were performed on 24 male, Wistar rats, weighing 240-260 g. In group I (n = 8) the supramaximal stimulation with i.v. caerulein (5 micrograms/kg/h) during 12 h was applied (C AP). Control animals (group II, n = 4) received i.v. saline (C-C). In group III (n = 8) 5% sodium taurocholate (0.2 ml/min) was injected into the bile-pancreatic duct during sterile laparotomy (T-AP). In group IV (n = 4) animals were sham operated (T-C). The specimens of the liver were excised after decapitation of rats at 12 h after beginning of caerulein infusion or intraductal injection of sodium taurocholate. The light and electron microscopy was performed. The marked hepatic lesion were found in both variants of experimental pancreatitis, however they were far more advanced in taurocholate pancreatitis. In light microscopy the dispersed foci of colliquative necrosis, degeneration of hepatocytes, swelling of Kupffer cells predominated in taurocholate pancreatitis. The glycogen deposits were depleted but lipid droplets were increased in size and number. The swelling of mitochondria, degeneration of their matrix and cristae, increase of autophagocytosis and numerous lysosomes, the lesions of sinusoids with increased activity of phagocytic cells were more evident in taurocholate pancreatitis- (more severe model of the disease). These findings document severe injury to the liver in acute pancreatitis depending on the severity of inflammatory process in pancreas. They also suggest that the liver could be not only passive target of pancreatogenic noxa in acute pancreatitis, but it could be also a defensive barrier against spreading of injuring agents on other system. This role seems to be especially evident in more severe form--taurocholate induced pancreatitis. PMID- 9972049 TI - Morphological brain damage, functional disorders and the possibilities of their treatment in children with infantile cerebral palsy. AB - Twenty-four children with infantile cerebral palsy (6 girls and 18 boys aged 3-17 years), surgically treated in the years 1993-1997, were involved in the study. Neurological-orthopaedic examinations and computer tomography (CT) of the head allowed precise diagnosis and understanding of its pathology. The group consisted of 10 patients with hemiplegia, 10 with diplegia and 4 with severe quadriplegia. In 18 children changes in the brain were largely dependent on the clinical type of paresis. In hemiparesis, unilateral changes, such as cerebral cortex atrophy with enlarged ventricles, were predominant. Diplegia cases frequently showed periventricular damage to the white matter. Brain tomography in severe quadriplegia did not always correspond to the clinical condition. CT examinations revealed no abnormalities in the brain in 6 out of 24 cases. Since the results of rehabilitation were not satisfactory, 29 surgical procedures were performed in the presented group of patients, with improved the course of therapeutic rehabilitation or nursing care in all the children. PMID- 9972050 TI - The influence of sex and selected paragenetic and environmental factors on the basic anthropometric measurements of newborns in Bialystok. AB - On the basis of retrospective analysis of 1913 deliveries (40-weeks, single, from healthy mothers) that took place in Bialystok hospitals from 1 January to 31 December 1997, the influence of sex and selected paragenetic and environmental factors on the somatic development of newborns was assessed. Mathematical description of the material was based on the following statistical methods: arithmetic mean (x), standard deviation (SD). In the assessment of significance of the obtained differences Student T test was used. The layout of empirical distribution curves of the examined parameters formed centile nets for the first born newborns. The analyses revealed that the influence of the genetic factor manifested by sexual dimorphism is the highest in case of body mass at birth. The pathogenic factors of the strongest influence included pregnancy and delivery. Age of parents had smaller effect on the somatic development of the foetus. The influence of the mother's puberty time on the somatic development of the foetus is an interesting phenomenon. Women who mature earlier give birth to bigger newborns compared to those with late puberty time. As far as the environmental factors are concerned, no influence of education level or place of residence of the parents on somatic condition of the foetus was observed. PMID- 9972051 TI - Maternal blood group in ABO and Rh systems and somatic condition of newborns. AB - Maternal blood group in ABO and Rh systems and somatic conditions of newborns. A group of 5454 eutrophic newborns (2649 female and 2805 male) from Bialystok were examined with respect to the following anthropometric features: body mass, crown rump length (Si), head and chest circumferences and their, relation to the maternal ABO and Rh blood groups. The mathematical description was done with the aid of computer (Statistica 4.0 for Windows) estimating statistical characteristics specific for mass phenomenon of regular distribution (x, SD). Significance of the obtained differences was evaluated with student t test. On the basis of the carried out research, it can be concluded that maternal blood group A may favor male newborns to have higher mean values of body mass, head and chest circumferences, and female newborns--of head circumference only. The crown rump length of newborns of both sexes does not show any alterations in relation to maternal blood group. Maternal Rh has no influence on the examined somatic development parameters of the newborns either. PMID- 9972052 TI - Type II alveolar epithelial cells and cyclophosphamide-induced lung fibrosis. AB - The aim of the study was to evaluate the quantitative and morphological changes in type II alveolar epithelial cells in the course of cyclophosphamide-induced lung damage. The experiments used 40 Wistar rats, of 170 g body weight. The animals were divided into two experimental groups. Group I animals were given cyclophosphamide (Endoxan-ASTA) in a single intraperitoneal dose of 150 mg/1kg b.w./1 ml PBS. Group II (control) received 1 ml PBS. All the animals were sacrificed after 1, 7, 14 and 28 days following intraperitoneal cyclophosphamide or PBS administration. Morphological examinations of pulmonary tissue were based on ultrastructural analysis in the transmission electron microscope. Quantitative studies of type II cells were performed basing on sections stained for alkaline phosphatase. The results of the quantitative analysis showed statistically significant alterations in the number of type II alveolar epithelial cells after 14 and 28 days following cyclophosphamide administration, compared with the respective control groups. The increase in the number of type II cells was accompanied by the intensification of fibroplasia processes within the interstitium of the interalveolar septa of the lungs. Ultrastructural exponents of active participation of type II cells in fibroplasia processes were found. PMID- 9972053 TI - Involvement of nitric oxide in cardiovascular effects of cholecystokinin (CCK) in rats. AB - The aim of the present study was determinate the role of nitric oxide (NO) in the action of CCK on arterial blood pressure and function of isolated rat heart. Intravenous administration of NO synthase (NOS) inhibitor-NG-nitro-L-arginine methyl ester (L-NAME-100.0 micrograms/kg) increased arterial blood pressure and abolished the hypertensive effect of CCK (administered in the highest dose: 425.0 pmoles/kg i.v.). Donors NO: L-arginine (L-Arg-100.0 mg/kg i.v.) and sodium nitroprusside (SNP-10.0 micrograms/kg i.v.) decreased arterial blood pressure, the hypotensive effect evoked by SNP was greater than produced by L-Arg. CCK administered with L-Arg evoked hypotension (opposite to the hypertensive effect evoked by CCK). When we used CCK at the higher doses (212.5; 425 pmoles/kg i.v.) simultaneously with L-Arg the hypotensive effect was greater than the hypotensive action evoked by L-Arg alone. Administration of CCK with SNP produced the hypotension (similar as after used SNP and opposite to the hypertensive action of the peptide). CCK (21.25, 42.5, 106.25 pmoles/0.1 ml) increased the cardiac contraction amplitude, the peptide injected in lower doses decreased coronary outflow. CCK had no effect on heart rate. L-NAME (10(-5) M) decreased coronary outflow, tendent to evoke bradycardia (p > 0.05) and the compound did not change the cardiac contraction amplitude of isolated heart. L-NAME abolished the influence of CCK on the function of isolated heart. L-Arg (10(-2) M) did not affect function of isolated heart. L-Arg abolished and when we used with CCK in the highest dose reversed the positive inotropic effect of the peptide and tendent to abolish a lowered coronary outflow evoked by CCK. SNP (10(-4) M) decreased the cardiac contraction amplitude. SNP diminished the positive inotropic effect of CCK and did not change other parameters of isolated heart. CONCLUSION: NO does not play a role in cardiovascular action of CCK directly, however inhibitor of NO synthase and donors of NO change the influence of the peptide, mainly on the heart. We suggest that the effect is indirectly through catecholamines. PMID- 9972054 TI - Overexpression of the nucleolar organizer regions (NORs) in the thyroid follicular tumours. Comparison of the cytological and histopathological examinations. AB - The aim of the study was to determine the usefulness of the expression of argyrophilic nucleolar organizer region proteins (AgNORs) as a marker of malignancy degree in thyroid follicular tumours. The study used the postoperative material of thyroid glands and cytologic material obtained with fine needle aspiration biopsy. Follicular adenoma, carcinoma and struma nodosa hyperplastica type changes were analysed. The comparison of the AgNOR parameters examined revealed statistically significant differences between the groups of follicular carcinoma and follicular adenoma, follicular carcinoma and nodular goitre, and between adenoma and nodular goitre. However, the "overlapping" of value ranges was observed between the groups of follicular carcinoma and adenoma, as well as follicular adenoma and nodular goitre. This referred particularly to atypical adenoma parameters found within a non-diagnostic range. No differences were observed in the counts of AgNOR dots between histologic and cytologic material obtained with fine needle aspiration biopsy. PMID- 9972055 TI - The activity of neutrophil myeloperoxidase in patients with renal cancer before and after embolization. AB - The activity of granulocytic myeloperoxidase (MPO) was investigated in 45 patients with renal cancer before and 14 days after renal artery embolization in comparison with control group of 40 healthy people. The group examined showed lower MPO activity before embolization, as compared to controls. The differences being statistical insignificant (p > 0.05). After embolization the activity MPO was normalized, reaching the mean value of control group. The findings revealed reduced granulocytic MPO activity in patients with renal cancer. PMID- 9972056 TI - Prolidase as a prodrug converting enzyme. II. Synthesis of proline analogue of anthraquinone-2-carboxylic acid and its susceptibility to the action of prolidase. AB - The feasibility to targeting prolidase as an antineoplastic prodrug--converting enzyme has been examined. The synthesis of proline analogue of anthraquinone-2 carboxylic acid (potential antineoplastic agent) conjugated through imido-bond (potential target for prolidase action) has been performed. The product was found to be insoluble in aqueous solution while in the presence of 1% DMSO complete solubility of the compound was achieved. Evidence was provided that 1% DMSO does not affect prolidase activity, thus allowing for substrate susceptibility measurement in a such conditions. It has been presented that product of synthesis, N-(anthraquinone-2-carbonyl)-L-proline evokes susceptibility to the action of purified prolidase, comparable to the susceptibility of glycyl-L proline (standard substrate for prolidase). Although insolubility of the proline analogue of anthraquinone-2-carboxylic acid in aqueous solutions limit its potential therapeutic value, the presented data suggest that prolidase may have a broader substrate specificity than thought previously. It suggests that targeting of prolidase as a prodrug-converting enzyme may serve as a potential strategy in therapy of neoplastic diseases. PMID- 9972057 TI - Western blot banding pattern in early Lyme borreliosis among patients from an endemic region of north-eastern Poland. AB - Aim of this study was evaluation of Western blot banding patterns in different clinical forms of early Lyme borreliosis diagnosed in patients from north-eastern Poland, recognized as endemic for tick-borne diseases. Study was performed on serum samples of 48 patients with Lyme borreliosis and 26 healthy volunteers, as controls. Samples tested routinely for total antibody with enzyme immunoassay were subsequently analysed for specific antibodies with Western blot based on antigen extract of European strain of Borrelia burgdorferi. In patients, IgM antibodies were the most frequently directed against 41 kDa and 58 kDa antigens, whereas in control group only antibodies against 45 kDa and 58 kDa were present. Similar response was observed in respect to IgG antibodies. Evaluation of banding pattern in respect to clinical form of the disease revealed the highest prevalence of IgM and IgG anti-41 kDa antibodies in patients with erythema migrans and Lyme arthritis, and anti-58 kDa in neuroborreliosis patients, who had no anti-21 kDa antibodies. Relatively high frequency of IgG antibodies against 21, 30 and 93 kDa antigens was typical for neuroborreliosis. Bands count was significantly higher in different clinical forms of the disease than in controls, and it was the highest in neuroborreliosis. Combined analysis of Western blot results (IgM/IgG) enabled to achieve higher sensitivity (84%) and specificity (100%) than available with the most recommended EIA kits. PMID- 9972058 TI - The activity of enzymes oxidizing alcohols in the liver of rats after methanol intoxication measured with fluorogenic substrates. AB - The activities of alcohol dehydrogenase isoenzymes (class ADH I and ADH II) and aldehyde dehydrogenase (ALDH) were measured using fluorogenic substrates in the liver of rats. Animals were dosed with 6 g of methanol/kg b.w. after 6, 12, 24 hours and 2, 5 and 7 days. Liver ADH I and ADH II activities were gradually increased after 6 h and up to 7 days after intoxication. ALDH activity in the liver had the highest elevation at 6 h, and then it decreased but was higher than the control value. It is concluded that subacute administration of methanol to rats leads to induction of hepatic enzymes involved in alcohols metabolism and that tested fluorogenic substrates are useful for these measurements. PMID- 9972059 TI - The influence of epsilon-aminocaproic acid derivatives on the anticoagulant activity of heparin. AB - Derivatives of epsilon-aminocaproic acid with antifibrinolytic activity, at low concentration, do not influence the anticoagulant activity of heparin under the heparin-thrombin test conditions. At concentrations higher than 0.002 M tested compounds slightly enhance the anticoagulant action of heparin. PMID- 9972060 TI - The mechanism of the silent zone on Lorenz plots in atrial fibrillation. AB - Lorenz plot is an acknowledged method of the evaluation of sequences of ventricular beats in cardiac arrhythmias, particularly in atrial fibrillation. Lorenz plots are scatterplots that show the R-R intervals as a function of the preceding R-R intervals. The authors of this paper conducted studies of 83 cases of atrial fibrillation; histograms of 500 consecutive R-R intervals were made, determining the mean R-R interval, the functional refraction period (FRP) of AV node and Lorenz plots. In 22 cases (26.5%) the presence of the silent zone on a Lorenz plot was observed, similarly to the study of Nakatsu and al. The silent zone appeared only in cases when the statistical distribution of R-R intervals was reflected by a bimodal histogram (less frequently by a trimodal histogram). The silent zone was never observed in cases of monomodal distribution of R-R intervals. The authors discuss Nakatsu's findings and argue that the silent zone in a Lorenz plot is a morphological expression of bimodal distribution of R-R intervals in atrial fibrillation. The silent zone may be caused by pharmacotherapy (e.g. digoxin), increased parasympathetic tension or other factors prolonging FRP. The presence of the silent zone is not a predictor of a spontaneous termination of atrial fibrillation. PMID- 9972061 TI - Cathepsin D inhibitor from Vicia sativa L. AB - Specific inhibitor of cathepsin D has been shown in the extract of Vicia sativa L. seeds. This inhibitor does not inhibit the activity of other aspartic proteases. Also it does not inhibit the activity of cysteine proteases and serine proteases. PMID- 9972062 TI - Effects of sulfated cholecystokinin octapeptide and cholecystokinin tetrapeptide in rat behavior after blockade of nitric oxide synthase by L-NAME. AB - This study was conducted to determine what, if any, role L-NAME (inhibitor of nitric oxide synthase) plays in the behavioral effects induced by sulfated cholecystokinin octapeptide CCK-8) and cholecystokinin tetrapeptide (CCK-4) in adult male rats. The motility, stereotypy, anxiety, extinction of conditioned avoidance responses and recall of passive avoidance behavior were estimated. CCK 8 (but not CCK-4) injected intracerebroventricularly (icv) at the dose 0.1 nmole decreased of locomotor activity in the "open field" test. Administration of CCK-8 intensified stereotypy evoked by apomorphine (1 mg/kg, i.p.). The CCK-4 was ineffective in this test. Both, CCK-8 and CCK-4 did not make any significant differences in passive avoidance behavior. Examine the influence of CCK-8 and CCK 4 on the extinction of conditioned avoidance responses (CAR) proved that both peptide tended to facilitate extinction of CAR's. CCK-8 and CCK-4 induced anxiogenic-like effect in the elevated 'plus' maze behavior. Application of L NAME alone (50 nmole,-icv) decreased of motility and stereotypy behavior in control rats. It was ineffective in a passive avoidance behavior and extinction of CAR's. In elevated 'plus' maze behavior injection of L-NAME, similarly to cholecystokinin, induced anxiogenic-like effect. L-NAME induced of motility decreases in the "open field" test were blocked by injection of CCK-8 and CCK-4. Our results indicate that observed behavioral activity of CCK-8 and CCK-4 (except of influence on motility) is probably independent of NO concentration in the brain. PMID- 9972063 TI - Epidemiology of erythema migrans in north-eastern Poland. AB - The aim of the study was to evaluate erythema migrans (EM) prevalence and treatment in north-eastern Poland during the last 25 years. The material for the study consisted of data sent to the Department of Dermatology by physicians from fifteen regional out-patient clinics. They were collected according to specially prepared questionnaires. The data were analysed with respect to the total number of EM cases, patients' age, seasonal prevalence of the disease, dynamics of its prevalence and treatment methods in successive years. Of the 262,421 case histories, retrospectively analysed 1235 EM cases (0.4%) were found. The age of the patients varied from 4 to 78 years. The highest incidence was observed between August and October (57.7% of all cases). The annual number of cases increased from only a few, in the years 1969-76, to over 436 in 1993. Penicillin or erythromycin were preferred for the treatment of EM before 1981, tetracycline or ampicillin between 1982-90, and amoxicillin or doxycycline in the last three years. Our results showed a significant increase in the number of EM cases in the dermatological clinics of north-eastern Poland in recent years. The treatment of the disease applied at present, complies with the generally accepted guidelines. PMID- 9972064 TI - Inhibitors of pepsin, trypsin and chymotrypsin in seeds of plants consumed by humans and animals. I. Evaluation of pepsin, trypsin, and chymotrypsin inhibitors activity in seeds of 26 plant species. AB - Antipepsin, antitrypsin and antichymotrypsin activity was determined in seed extracts of 26 plants consumed by humans and animals (small bean, broad bean, pumpkin, kidney bean, charlock, pea, buckwheat, barley, maize, flax, lupine, poppy, almond, peanut, hazel, walnut, oat, millet, wheat, rice, rape, sunflower, lentils soya bean, vetch, rye). Antipepsin activity is found in the seeds of small bean, pumpkin, flax, peanut, walnut, oat, wheat, sunflower, lentils and soya bean. Antitrypsin and antichymotrypsin activities are of different intensity in seed extracts of all examined plants. PMID- 9972065 TI - Nitrates and nitrites contents in whole-day's diets of men--workers of metal industry. AB - An evaluation of nitrates and nitrites in daily diets of 239 men was performed. It was found that daily intake of these compounds did not exceed the acceptable values. PMID- 9972066 TI - Nitroblue tetrazolium test in patients with renal tumor in the course of embolization. AB - The main role of neutrophilic granulocytes is phagocytosis and destruction of phagocytized bacteria. The nitroblue tetrazolium test (NBT), used to evaluate the bactericidal function of granulocytes, was assessed in 45 patients with renal tumour before and 14 days after renal artery embolization. No statistically significant spontaneous test NBT differences were found, compared with control group both before and 14 days after embolization. Following stimulation granulocytes in vitro by LPS of E. coli the ability of granulocytes to reduce NBT was lowered. The differences, as compared with control group, were statistically significant (p < 0.05). Our results indicates considerable impairment of lower metabolic reserve in patients with renal tumour necessary for maximum stimulation. PMID- 9972067 TI - Fetotoxic effect of 2,4-dichlorophenoxyacetic acid (2,4-D) in rats. AB - The fetotoxic effect of 2,4-dichlorophenoxyacetic acid (2,4-D) was investigated. Histological and histochemical changes in the liver of newborn, jung and adult rats exposed to the herbicide from the prenatal period to the end of an experiment were evaluated. The experiment used 90 male and female, Wistar, aged to 10 weeks rats, divided into two groups: I-control-30 and II-60 animals which received the water solution of 2,4-D acid sodium salt in a daily dose of 250 mg/kg b.w. It was given with drinking water every day. The animals were sacrificed after 24 hours, 4, 6, and 10 weeks of the experiment. The results obtained showed that the administration of 2,4-D acid to rats in the prenatal and postnatal period, in a dose inducing subacute intoxication leads to histological and histochemical changes in the liver. The observed changes indicate disorders in energetic processes in hepatocytes and are morphological exponents of detoxicative processes there. They are most intensified with newborn rats. It suggest also, the pregnants ought not to work with 2,4-D and should avoid any contact with herbicides belongs to the 2,4-dichlorophenoxyacetic acid group. PMID- 9972068 TI - Metallothioneins in rats exposed to cadmium. AB - It was found that intoxication of rats with cadmium results in a significant increase of metallothioneins content in various organs, especially in kidneys and liver and in lower degree in spleen, muscle, brain and heart. PMID- 9972069 TI - Ultrastructural changes in rat hepatocytes in acute intoxication with 2,4 dichlorophenoxyacetic acid (2,4-D). AB - The hepatotoxic effect of 2,4-dichlorophenoxyacetic acid (2,4-D) was investigated. Ultrastructural changes were evaluated in transmission electron microscope. The experiment used 60 male Wistar rats divided into two groups: I- control-18 animals and II--42 animals which received chemically pure 2,4-D acid by gastric gavage in a dose of 200 mg/kg b.w. The animals were sacrificed after 12, 24, 48 hours and 4, 10 and 30 days of the experiment. The results obtained indicate that the administration of 2,4-D acid to rats in a dose inducing acute intoxication leads to ultrastructural changes in the liver, which suggest nonspecific reversible adaptative-type damage to parenchymal cells. The changes observed indicate disorders in energetic processes in hepatocytes and are morphological exponents of detoxicative processes there. PMID- 9972070 TI - Breastmilk nucleotides. PMID- 9972071 TI - Blood lead levels in children with neurological disorders. AB - Blood lead levels were measured by atomic absorption spectrometry in 82 children suffering from various neurological disorders (cerebral palsy 42, seizure disorders 35, acute encephalopathy of unknown origin 5) and in 28 healthy children, aged 1 to 12 years. Mean blood lead levels were 11.96 +/- 10.97 micrograms/dl in control children and 19.30 +/- 17.65 micrograms/dl in children with neurological disorders. A significant number of control children as well as those who had neurological disorders were found to have blood lead concentrations of > or = 10 micrograms/dl and > or = 20 micrograms/dl, the cut-off limits for lead poisoning and medical evaluation, respectively. Blood lead levels were, statistically, elevated in children with cerebral palsy compared to controls. Children with pica behaviour exhibited higher blood lead concentrations. PMID- 9972072 TI - Anaemia and intestinal parasitic infections among school age children in Behera Governorate, Egypt. Behera Survey Team. AB - Anaemia is considered a serious public health problem in Egypt, although updated population-based data are lacking. Similarly, data on prevalence and intensity of infection with intestinal parasites, which are considered one possible cause of anaemia, are available only from small, unrepresentative sample surveys. The present research was implemented on an entire Governorate representative sample. The aim of the study was to assess the prevalence of anaemia and intestinal parasites in the area and to evaluate the role of each parasite in the epidemiology of anaemia among school age children. At the end of the survey, results of faecal analyses from direct smear and the Kato-Katz examination techniques were available from 1844 and 1783 children respectively, as well as haemoglobin levels measured by spectrophotometer from 1238 children aged 6-12 years. The prevalence of anaemia in the area was high (90 per cent), but very few serve forms were detected (< 2 per cent). Prevalence of intestinal parasites was high only for protozoa (Giardia intestinalis 24.7 per cent Entamoeba histolytica 17.5 per cent) and Schistosoma mansoni (20.7 per cent). From analysis of the results, Fasciola infection appeared to be highly endemic, even among children (3 per cent), and emerged as the factor most strongly correlated with low levels of haemoglobin (p < 0.0001). The effect of Fasciola on haemoglobin levels was related to the intensity of infection with this parasite. The role of S. mansoni as a risk factor for anaemia was supported by the present study. Among the protozoa, G. intestinalis was significantly correlated with low haemoglobin levels (p < 0.05). The present results substantiated similar findings from smaller studies. In future research, the relationship between Fasciola infection and anaemia needs to be studied with a well-controlled longitudinal design. PMID- 9972073 TI - Survival analysis for cystic fibrosis in Minas Gerais State, Brazil. AB - A survival analysis was carried out on cystic fibrosis (CF) patients diagnosed and followed at the General Hospital, Federal University of Minas Gerais, Brazil. The study cohort consisted of 111 children, admitted to the Pediatric Pulmonology Section from 1 June 1970 to 31 December 1994. The survival curve and table, constructed by the Kaplan-Meier (product limit) method, show a mean survival age of 12.6 years. This life expectancy resembles the median survival age observed in developed countries by 1970. This study shows that problems relating to health system organization and unfavourable social and economic conditions in developing countries may directly affect the ultimate survival of CF patients. PMID- 9972074 TI - Comparison of survival of diarrhoeagenic agents in two local weaning foods (ogi and koko). AB - The pH values of both cooked and uncooked ogi and koko samples were determined and the survival rate of four diarrhoeagenic agents, enteroinvasive Escherichia coli, Salmonella typhi, Shigella flexneri, and Vibrio cholerae were studied after they were seeded into cooked ogi and koko. Analysis of the pH of the cooked inoculated samples showed that there was a slight increase in pH (decrease in acidity) during storage for 48 h and 37 degrees C (from 3.5 to 3.7 for ogi and from 3.7 to 4.1 for koko). The study also showed that ogi had a slightly lower pH value than koko both before and after cooking. In both cases, the cooked samples had a slightly lower pH value than the uncooked samples. The pH value of ogi ranged from 3.0 to 3.6 and that of koko from 3.5 to 3.9. The survival experiment showed that the inoculated enteric pathogens were inhibited in cooked ogi and koko during storage for 24-48 h. The antibacterial effect of cooked koko was more pronounced, on the four enteric pathogens studied, than that of cooked ogi. Except for Shigella flexneri and E. coli in ogi, non of the other bacteria studied was recovered after 24 h. PMID- 9972075 TI - Contamination of weaning foods: organisms, channels, and sequelae. AB - A study was carried out to identify the microbial contaminants of weaning foods in an Egyptian village and the sources of contamination. All 300 households containing infants (< 24 months) were visited. Information regarding food preparation and household sanitation was gathered. Samples of weaning foods (270) were collected and analysed for the presence of Escherichia coli, Bacillus cereus, Shigella and parasites. The first two pathogens were detected in 43.7 per cent and 21.4 per cent of samples respectively. The others were not detected in any sample. The risk of contamination by E. coli and B. cereus was significantly associated with the presence of dung and/or refuse in the house, lack of indoor latrine, non-use of latrine by children, weaning foods not freshly prepared, uncovered storage of foods, and the presence of a case of diarrhoea in the house. PMID- 9972076 TI - Isolation of pathogenic bacteria from induced sputum from hospitalized children with pneumonia in Bangladesh. AB - A prospective study was carried out on 157 patients admitted to a paediatric hospital in Dhaka, Bangladesh to determine the bacteria present in the induced sputum of paediatric patients with X-ray proven pneumonia. Their ages ranged from 21 days to 11 years; 65 per cent of them were male and 35 per cent were female. The most affected age group was between 6 months and 2 years old. Respiratory secretions produced by induced cough were taken by swab from the oropharynx for culture and smear. The predominant bacteria were Haemophilus influenzae, Streptococcus pneumoniae, Branhamella catarrhalis and Gram-negative bacilli. Serotyping of H. influenzae revealed that 76 per cent were non-typable and 18 per cent were of type b; 23.5 per cent of isolates of H. influenzae were beta lactamase producing. MIC90 of penicillin against S. pneumoniae and H. influenzae were 0.025 and 3.13 micrograms/ml respectively. Ampicillin, penicillin G (benzylpenicillin), amoxycillin, and gentamicin were administered for the treatment of these patients. All cases were apparently improved, on the basis of clinical evaluation, and discharged from the hospital. PMID- 9972077 TI - Outcome for children under 5 years hospitalized with severe acute lower respiratory tract infections in Yemen: a 5 year experience. AB - Between 1991 and 1995, 2554 children under 5 years old hospitalized with severe acute lower respiratory tract infection in Al-Sabe'en, Sana'a, Yemen were studied. 47.7 per cent (1218) were under 6 months of age and 74.1 per cent (1893) were in their first 12 months. Sixty-four per cent (1633) were males. Of the 2554 cases, 221 died (overall, a case fatality rate of 8.7 per cent). 118 of the deaths (53.4 per cent) were in the under 6 months age group and 188 (85 per cent) were in the first 12 months age group. During 1995 the hospital started adopting the WHO standard case-management guidelines for treating severe acute lower respiratory tract infections. There were no significant reductions in case fatality rates in 1995 (CFR 9.8 per cent) compared with those of 1991 (CFR 7.9 per cent), 1992 (CFR 9.4 per cent), 1993 (CFR 7 per cent), or 1994 (CFR 8.5 per cent). Factors such as late hospital admission with cyanosis, malnutrition, rickets as well as increased resistance of the common causative organisms (pneumococci and H. influenzae) to antibiotics recommended by the WHO may have contributed to such a high case fatality rate remaining unchanged. In addition to reducing the risk of developing pneumonia and dying from pneumonia by improving maternal nutrition, health education, promoting breastfeeding, and preventing rickets and nutritional anaemia among the vulnerable age groups, vaccination against pneumococci and H. influenzae type b should be seriously considered as one of the strategies to reduce lower respiratory tract infection-related mortality. PMID- 9972078 TI - Secular changes in rates of respiratory complications and diarrhoea among measles cases. AB - It has been observed that the occurrence of respiratory complications and diarrhoea among measles cases has changed over time but this change has not been quantified. A study was carried out in the city of Gweru, Zimbabwe, to quantify these changes. Rates of respiratory complications and diarrhoea among measles cases were determined in each year for the period 1968-89. It was found that mean rates of respiratory complications and diarrhoea during 1968-78 were 17.2 per cent (95 per cent CI = 11.6-22.8) and 5.2 per cent (95 per cent CI = 0-11) respectively while during 1979-89, mean rates of respiratory complications and diarrhoea were 6.5 per cent (95 per cent CI = 1-12.1) and 16.4 per cent (95 per cent CI = 10.1-22.0) respectively. Analysis of variance (ANOVA) to determine the main effects and the interaction showed that the main effects were not statistically significant (F = 0.01, d.f.1,2 = 1,40, p = 0.935; and F = 0.13, d.f.1,2 = 1,40, p = 0.725 respectively) Meanwhile the interaction term of complications and period was statistically significant (F = 15.7, d.f.1,2 = 1,40, p < 0.001). It was concluded that a change in rates of respiratory complications and diarrhoea had occurred among measles cases. It is suggested that the increase in vaccination coverage in 1979-89 and the shift in age at infection to older age groups in the same period may have brought about this change through selective suppression of respiratory complications among measles cases. PMID- 9972079 TI - Clinical patterns of neuronal migrational disorders and parental consanguinity. AB - The role of inheritance in neuronal migrational disorders is under intense investigation. Studies on neuronal migrational disorders (NMDs) from developing countries that have a high rate of parental consanguinity are lacking. The present study included 29 children (aged 15 days-12 years, mean age 1.4 years) who were diagnosed to have NMDs, from a non-selected population with seizures and non-selected population of cognitive developmental delay, in the period January 1994 to April 1997. Seventeen (58.6 per cent) patients had lissencephaly, four (13.8 per cent) patients had pachygyria, three (10.3 per cent) patients had neuronal heterotopia, four (13.8 per cent) patients had schizencephaly, one patient (3.4 per cent) had hemimegalencephaly, and 14 (48.2 per cent) patients with NMDs had other associated conditions. Lissencephalic patients had a high rate of parental consanguinity (88.2 per cent) and family history of possible similar cases (76.4 per cent). In conclusion, lissencephaly is probably the commonest neuronal migrational disorder in communities with a high rate of parental consanguinity, adding significant support to the literature on the genetic aetiology of lissencephaly. PMID- 9972080 TI - Weight, length, ponderal index, and intrauterine growth retardation in Brazil. AB - The objective of this study was to classify intrauterine growth-retarded (IUGR) newborn babies from an urban region in Brazil into four different subtypes, according to their weight, length, and ponderal index (PI). Three hundred and fifty-six (356) babies were differentiated by this classification into IUGR subtypes A (short length and adequate PI), B (adequate length and low PI), C (short length and low PI), and D (adequate length and adequate PI), by the Lubchenco weight, length, and PI for gestational age standards. Gestational age of the babies was determined by the Capurro method. Anthropometric measurements were taken according to the Jelliffe and Jelliffe recommendations. Ninety-eight per cent of the IUGR babies included in the study were type I (proportional): 48 per cent of them were subtype A and 50 per cent subtype D (slightly thin). Subtypes B and C comprised 1.4 per cent and 0.6 per cent of the babies respectively. This classification of IUGR is of great importance, considering that these four subtypes probably reflect the stages of pregnancy at which the babies were affected by adverse growth and development factors. The risk factors for the different subtypes of IUGR, and examination of their predictive value for subsequent morbidity, growth, development, and mortality, will be of interest. PMID- 9972081 TI - Cause-specific mortality in under fives in the urban slums of Lucknow, north India. AB - We recorded the causes of death in the preceding 3 years in a slum population of 24,196 children less than 5 years of age in Lucknow, North India. Of 1469 deaths recorded, 298 were stillbirths. For each death, a 'verbal autopsy' was conducted by interviewing the parents to ascertain the cause of death. 71.8 per cent of deaths were at home; 94.5 per cent of hospital deaths had no death certificate. Excluding stillbirths, 69.9 per cent of deaths were in the first year of life. Leading causes of death in the neonatal period were prematurity (38.5 per cent) and tetanus (36.4 per cent). Beyond the neonatal period, the leading causes of death were pneumonia (23.4 per cent), diarrhoeal disease (20.9 per cent), and malnutrition and/or anaemia (11.4 per cent). The existent mortality-recording system was under-reporting at least one third of the deaths. We conclude that stillbirths and neonatal mortality can be reduced by improved antenatal and natal care. In the postnatal period, since most of the mortality is due either to infective diseases or malnutrition, interventions to improve the nutritional status of preschool children can reduce this. PMID- 9972082 TI - Study of plasma albumin, transferrin, and fibronectin in children with mild to moderate protein-energy malnutrition. AB - With the increasing awareness of incipient and subclinical malnutrition in children several nutritional indices have been suggested for the early recognition of protein-energy malnutrition (PEM). We evaluated plasma albumin, transferrin, and fibronectin levels in 15 children with PEM and compared them with those of 10 well-nourished children. The results demonstrated that plasma albumin is a poor indicator of mild to moderate PEM. On the other hand, plasma transferrin and fibronectin are sensitive indicators of PEM as they were significantly decreased in our mild to moderately malnourished children whereas albumin was unchanged. Furthermore, malnourished children showed iron deficiency anaemia, which may interfere with the results of plasma transferrin determinations. Fibronectin is believed to have a functional role in coagulation, host immune defence, and wound healing. We suggest that the assay of fibronectin may provide a biochemical functional index of mild to moderate nutritional deficiency before overall depletion has occurred. PMID- 9972083 TI - Comparison of nasal prongs with nasal catheters in the delivery of oxygen to children with hypoxia. AB - Efficient, inexpensive, and safe methods of oxygen delivery are needed for children with severe pneumonia in developing countries. The objective of this study was to estimate the frequency of complications when nasal catheters or nasal prongs are used to delivery oxygen. Ninety-nine children between 2 weeks and 5 years of age with hypoxia were randomized to receive oxygen via nasal catheter (49 children) or nasal prongs (50 children). There was no difference in the incidence of hypoxaemic episodes or in the oxygen flow rates between the two groups. Mucus production was more of a problem in the catheter group. Nasal blockage, intolerance to the method of administration, and nursing effort were generally higher amongst the catheter group, but these differences were not significant, except for nursing effort, when all age groups were analysed together. PMID- 9972084 TI - Epidemiologic consequences of moderate coverage levels of measles vaccine in a district headquarter town (Alwar) in India, 1996. AB - This paper describes the epidemiology of measles in a medium size town (population 240,000) in India where vaccine coverage levels have remained constant at around 70 per cent in the past 7 years. A retrospective community survey covering 4023 children under 10 years old detected 252 cases of measles in the previous year. This gave an annual incidence of 6.3 per cent (95 per cent CI 5.5-7). About half of the cases occurred in vaccinated children. Only 5 per cent of the cases occurred in children below 9 months of age. This age is appropriate for routine measles immunization. Despite modest coverage levels with only 54 per cent effective vaccine (estimated by a screening method), there was a modest upward shift in the age distribution of measles cases; the median age was more than 48 months. PMID- 9972085 TI - Findings of colonoscopy in children: experience from Kuwait. AB - This report summarizes our retrospective analysis of 173 colonoscopic examinations performed on 159 children over a period of 9 years in Kuwait. Ninety six children were males, with a male to female ratio of 1.5:1. The main indications for colonoscopy were rectal bleeding, polyps, and suspected inflammatory bowel disease. Examination was done under sedation or anaesthesia. One hundred and fifty-one (87 per cent) examinations were complete up to the caecum and 89 (51 per cent) up to the terminal ileum. The most common pathology was polyps in 42 children. All but one polyp were hamartomatous and mainly localized to the rectum and sigmoid colon. The majority had a single polyp. One child had adenomatous polyposis coli. One hundred and forty-two polyps were removed endoscopically with no complications. Inflammatory bowel disease was present in 34 (21 per cent) children (17 Crohn's disease, 11 ulcerative colitis, and 6 indeterminate colitis). Tuberculosis of the ileo-caecal region was diagnosed in two cases. Seven patients had rectal ulcers presenting as rectal bleeding. In 11 (7 per cent), the lesions were limited to the right side of the colon or terminal ileum. These results suggest that colonic pathology is not uncommon in children in Kuwait. The disease pattern is similar to that reported in western countries. As we have observed in adults, inflammatory bowel disease is seen in significant numbers among children in this region. In this survey we have observed a change in the disease frequency, Crohn's disease being more common that ulcerative colitis. Without adequate examination, the existence of inflammatory bowel disease and this possible changing pattern of disease would have gone unrecognized. PMID- 9972086 TI - Prevalence of hepatitis B surface antigen (HBsAg) in children with sickle cell anaemia. PMID- 9972087 TI - Sentinel surveillance of Chlamydia trachomatis in school-going girls vis-a-vis women with secondary infertility. PMID- 9972088 TI - Blood transfusion in preterm infants and risk of oxygen radical injury. PMID- 9972089 TI - Preparing residents to give a deposition just got a little easier. PMID- 9972090 TI - Broader picture surrounding new pediatric labeling for topical corticosteroid therapy. PMID- 9972091 TI - Manipulation for low back pain ahead of its time ... but now is the time. PMID- 9972092 TI - Timing of hysterectomy surgery during the menstrual cycle--impact of menstrual cycle phase on rate of complications: preliminary study. AB - To determine the relationship between the timing of a hysterectomy performed during the menstrual cycle phase and the postoperative complication rate in women who had undergone surgery for dysfunctional uterine bleeding, the authors examined the charts of 24 patients for the 3-month period immediately after the hysterectomy. Twelve of the women were in the follicular phase, and 12 were in the luteal phase at the time they had undergone the hysterectomy. Patients were classified by operative pathology report. No significant differences (P < or = 0.05) were found between the two groups with respect to age, weight, para status, pathology, preoperative and postoperative hemoglobin levels, operation time, blood loss, days before return to full functioning, days in hospital, and uterine morphology. Further prospective studies with longer follow-up time are needed to obtain more conclusive indications regarding the optimal timing of hysterectomy during the menstrual cycle. PMID- 9972093 TI - Method of preparing emergency medicine residents for giving legal depositions. AB - This study was performed to determine if a simulated legal deposition increases emergency medicine (EM) residents' knowledge, self-confidence, and understanding of a legal deposition. This prospective study included a convenience sample of EM 1-3 residents. A knowledge and a self-assessment pretest were given, followed by a didactic session moderated by local attorneys, followed by knowledge and a self assessment posttest. The total time involved was 2 hours. The mean score on the knowledge pretest was 4.5 and 5.25 on the posttest. Using a paired t-test, the authors found this difference to be statistically significant. (P < 0.01) Using Hotelling's T2 test, the authors compared presimulation and postsimulation self assessment questions. The results revealed that there was a difference between these scores (P < 0.001). Participants in the deposition significantly improved their self-assessment ranking and knowledge inventory test scores by participating in a simulated legal deposition. PMID- 9972094 TI - Oklahoma physician needs. AB - State policy makers, healthcare professionals, and advocates have been asking various iterations of the question, Do we have too many or too few physicians? In order to address this question, a relative-needs analysis was conducted for the state of Oklahoma. Six projection-needs studies were used for comparison with Oklahoma's supply of practicing physicians. This analysis found that Oklahoma did not have a surplus of primary care physicians. While the national average for primary care physicians per 100,000 was 79, Oklahoma's ratio was 68. This analysis also compares not only the number of physicians in Oklahoma per 100,000 population, it also discusses the proportion of primary care physicians in the physician workforce. Primary care physicians were found to be neither oversupplied nor undersupplied in Oklahoma. Oklahoma was found to be closer to national planning model goals than most states in the United States. Because this study combines both allopathic and osteopathic physicians and includes only those physicians in active practice, it is unique in comparison to many other studies concerning physician workforce needs. PMID- 9972095 TI - A problem with synthetic maps. AB - Synthetic maps of human gene frequencies, which are maps of principal component scores based on correlation of interpolated surfaces, have been popularized widely by L. Cavalli-Sforza, P. Menozzi, and A. Piazza. Such maps are used to make ethnohistorical inferences or to support various demographic or historical hypotheses. We show from first principles and by analyses of real and simulated data that synthetic maps are subject to large errors and that apparent geographic trends may be detected in spatially random data. We conclude that results featured as synthetic maps should be approached with considerable caution. PMID- 9972096 TI - Genetic studies in 5 Greek population samples using 12 highly polymorphic DNA loci. AB - Two minisatellite (D1S80, D17S5) and 10 microsatellite (D2S1328, TPO, D3S1358, D9S926, D11S2010, THO1, VWF, FES, D16S310, and D18S848) polymorphic loci were analyzed in 5 Greek population groups (eastern Macedonia, central Macedonia, Thessaly, Epirus, and Greeks from Asia Minor) using the polymerase chain reaction. The genotypes at these loci conformed to Hardy-Weinberg equilibrium, and pairwise comparisons between them were in agreement with the expectation of independence between loci. This along with the low values of the coefficient of gene differentiation (GST) and the high heterozygosity levels of all loci allows the use of allele frequency data from the 12 hypervariable DNA markers for medicolegal casework in the Greek population groups studied. The small genetic distances indicate a genetic affinity among the 5 population samples. However, a few markers seem to allow some discrimination among the groups. No significant differences with other European populations were found for the loci studied. PMID- 9972097 TI - Analysis of 6 short tandem repeat loci in Navarre (northern Spain). AB - A genetic study was performed on a sample of 146 autochthonous individuals from the province of Navarre (northern Spain) to test for 6 STR systems: CSF1PO, TPOX, TH01, F13A1, FES/FPS, and VWA31/A. The Navarre population has a series of allele frequencies that are at the extreme end of the European range of variation and that are in most cases similar to those found in the Basque population of the provinces of Alava, Biscay, and Guipuzcoa. This similarity is corroborated by correspondence analysis, in which the population of Navarre is at one end of the first axis with the Basque sample close to it and the remaining European populations far removed. In tree-type representations the Navarre population is grouped with the Basque series at 1 end. Even so, the comparison of allele frequency distributions by the chi-square heterogeneity test indicates that these 2 groups are statistically different. Our results together with the cultural relationship that exists between all the Basque-speaking provinces and the genetic heterogeneity described in earlier studies between the Basque provinces of Alava, Biscay, and Guipuzcoa (Aguirre et al. 1989; Manzano, Orue et al. 1996; Manzano, Aguirre et al. 1996) lead us to believe that the Navarre population lies within the heterogeneous Basque genetic map. PMID- 9972098 TI - Stability of the FMR1 CGG repeat in a Basque sample. AB - The fragile X syndrome is an X-chromosome-linked dominant disorder with reduced penetrance. It is the most common inherited form of mental retardation. The molecular basis is usually the unstable expansion of a CGG trinucleotide repeat in the 5' untranslated region of the first exon of the FMR1 gene, which resides at chromosome position Xq27.3 and is coincident with the cytogenetic fragile site FRAXA, which characterizes the syndrome. In the Biscay province of the Basque Country the prevalence of FRAXA in a mentally retarded sample of non-Basque origin is in the range of other analyzed Spanish populations. In the sample of Basque origin we have not found FRAXA site expression and the repeat size is in the normal range. Based on this, we have examined FMR1 gene stability in normal individuals of Basque origin from the Biscay province. This study is based on a sample of 242 X chromosomes. The results from the CGG repeat region of FMR1 indicate that a prevalence of predisposing normal alleles toward repeat instability in the Basque population is 0.00% or near to it. This could be 1 of the explanations of the apparently low fragile X syndrome incidence found in the Basque mentally retarded sample analyzed by us. This low incidence does not seem to be associated with the flanking microsatellite markers. PMID- 9972099 TI - Genetic polymorphisms and ethnic admixture in African-derived black communities of northeastern Brazil. AB - Unrelated individuals from 3 relatively isolated African-derived communities in the state of Piaui, northeastern Brazil, and blood donors from Teresina (admixed population), the capital city of Piaui, were analyzed for the ESD, CA2, GC, HP, GLO1, PGM1, HB, ACP1 protein loci and for the VWF1 and VWF2 short tandem repeat (STR) loci. As expected, high frequencies of alleles considered characteristics of African populations were detected. The VWF1 allele distribution was bi-modal, whereas the VWF2 distribution was unimodal, suggesting differential action of mutation and selection factors in the 2 STRs despite their close location on the same gene. The genetic distances between the Brazilian isolates coincide with their geographic distances. The ethnic admixture estimated by a maximum likelihood method showed African, European, and Amerindian components of 61%, 17%, and 22% for Mimbo, 72%, 12%, and 16% for Sitio Velho, and 31%, 21%, and 48% for Teresina, respectively. PMID- 9972100 TI - Apolipoprotein B genetic variability in Brazilian Indians. AB - Three apolipoprotein B restriction fragment length polymorphism (RFLPs) (XbaI, MspI, and EcoRI) and the signal peptide insertion-deletion polymorphism were investigated using the polymerase chain reaction in 140 individuals from 5 Brazilian Indian tribes. All studied markers were polymorphic in this ethnic group. The insertion allele 5' beta SP*29 at the signal peptide previously observed in Mexican Americans was detected in about 8% of the chromosomes of 2 tribes (Gaviao and Zoro), therefore confirming the Amerindian origin of this allele. Negative linkage disequilibrium was observed between alleles at the signal peptide and the EcoRI polymorphism in all tribes. In 3 populations (Gaviao, Surui, and Zoro) a negative disequilibrium was also detected between the insertion-deletion signal peptide markers and the XbaI polymorphism. In the whole sample of Amerindians 14 of the 24 (58%) possible 4-marker extended haplotypes were identified, but only haplotype 2 (5' beta SP*24/*X+/*M+/*E+) and haplotype 5 (5' beta SP*27/*X-/*M+/*E+) were shared by all tribes. No associations between plasma lipid levels or body mass index and these polymorphisms were observed in this sample. PMID- 9972101 TI - One founder/one gene hypothesis in a new expanding population: Saguenay (Quebec, Canada). AB - High frequencies of some rare inherited recessive disorders can be found in the Saguenay region of Quebec, Canada. Four disorders have a carrier frequency of about 0.04 (in the range 0.035-0.05): pseudovitamin D-dependent rickets, hereditary tyrosinemia type 1, Charlevoix-Saguenay spastic ataxia, and sensorimotor polyneuropathy with or without agenesis of the corpus callosum. Molecular data suggest that only 1 mutation has been introduced into the population since its founding in the 17th century. The carrier frequencies are much higher than one would expect under a theoretical model that includes variance in family size and population growth (Thompson and Neel 1978). I present a methodology called allele dropping to test the hypothesis that only 1 founder introduced a given mutation. This study is based on 891 ascending genealogies and enables one to measure the extent of allele frequency changes resulting from the demographic history of the population. Two scenarios are tested: neutral and lethal alleles. Lethality has a minor effect because the alleles never reach a frequency high enough for selection to be strong. Twenty-five founders have a probability greater than 1% that a lethal mutation they introduced into the population will reach a carrier frequency between 0.035 and 0.05 in the contemporary population. Moreover, 2 founders have a probability greater than 20% that a lethal allele they introduced into the population will reach this target frequency. Therefore the simplest hypothesis that 1 founder introduced 1 disorder into the population is consistent. PMID- 9972102 TI - Geographic heterogeneity of 4 common worldwide cystic fibrosis non-DF508 mutations in Brazil. AB - Cystic fibrosis (CF) is an autosomal recessive disease caused by at least 750 different mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. The frequency of the most common mutation (DF508) in Brazilian patients of European origin is 47%. To determine the frequency of 4 other common CF mutations (G542X, G551D, R553X, and N1303K) in Brazilian patients of European origin, we used direct polymerase chain reaction (PCR) amplification of DNA obtained from dried blood spots on Guthrie cards. The DNA came from 247 non-DF508 chromosomes from 172 Brazilian CF patients ascertained from 5 different states of Brazil. The results show that the 4 mutations account for 17% of the non-DF508 alleles and only 9% of the total number of Brazilian CF alleles. Overall, the frequency of each mutation is different from northern European and North American populations but similar to southern European populations, mainly the Italian and Spanish populations. When Brazilian patients of European origin are grouped according to state of birth, the frequencies of the mutations are significantly different between southern and southeastern states of Brazil. Therefore there are serious implication for risk assessment of DNA-based tests in heterogeneous populations such as Brazilians. Further studies are needed to identify the remaining 44% of CF mutations for the different populations and regions of Brazil. PMID- 9972103 TI - Changes over 100 years in degree of isolation of 21 parishes of the Lima Valley, Italy, assessed by surname isonymy. AB - Changes over 100 years (1887-1986) in degree of isolation of 21 parishes of the Lima valley, Italy, were assessed using surname analysis. Crow and Mange's inbreeding coefficients and Lasker and Kaplan's repeated pair values were calculated using 8026 marriage records; temporal changes were assessed by dividing birth cohorts into 4 time periods of 25 years each: 1887-1911, 1912 1936, 1937-1961, and 1962-1986. Analysis was carried out at 2 hierarchical levels: the population of the valley as a whole and the valley's subdivision into 21 parishes. The relationship between population size and level of isonymy during the breakdown of isolates was investigated. The results show that there is a small difference in inbreeding coefficients between the first 2 periods at either hierarchical level of analysis and a substantial decrease in marital isonymy during the study period is mostly due to the change in male random isonymy. Furthermore, the Fn value at the higher hierarchical level almost coincides with the mean F value at the lower hierarchical level, indicating that over time the parish remained the fundamental reproductive unit. Regression analysis showed that geographic isolation became increasingly important in differentiation among the parishes in population size and in levels of inbreeding. The marked deviation from equilibrium between drift and migration that characterizes the breakdown of isolates of almost all the rural populations is an important disturbing factor in assessing the relationship between level of inbreeding and population size. Comparison over time allows us to better describe the evolutionary forces at the basis of the changes in genetic structure of a population. PMID- 9972105 TI - A vaccine against Lyme disease. PMID- 9972104 TI - Sex ratio and parental age gap. AB - We tested the hypothesis that a large age difference between parents can shift the sex ratio at birth in favor of males, as Manning et al. (1997) suggested in their analysis of English and Welsh data. Among children born in Lombardy (northern Italy) in 1990 and 1991, we observed an anomalous excess of males born to a particular subsample of parents with a wide age gap (> 15 yr) between them; in the overall sample the father-mother age gap does not significantly contribute to the determination of the child's sex. PMID- 9972106 TI - Antibiotics for frequent indigestion? PMID- 9972107 TI - Preventive mastectomy. PMID- 9972108 TI - CT for detecting heart disease. PMID- 9972109 TI - Nasal sprays best for treating hay fever. PMID- 9972110 TI - Animal bites and infection. PMID- 9972111 TI - Fosamax prevents fractures--for some. PMID- 9972113 TI - Cast off sooner with new bone cement. PMID- 9972112 TI - Intensive heart program seeing results. PMID- 9972114 TI - Zeroing in on attention deficit disorder. PMID- 9972115 TI - Non-Antibiotic Properties of Tetracyclines. Proceedings of a Symposium. Garden City, New York, November 13-14, 1997. PMID- 9972116 TI - Chemical and biological dynamics of tetracyclines. PMID- 9972117 TI - Tetracyclines inhibit connective tissue breakdown by multiple non-antimicrobial mechanisms. AB - A seminal experiment involving a germ-free rat model of connective tissue breakdown (followed soon thereafter by a series of in vitro studies) identified an unexpected non-antimicrobial property of tetracyclines (TCs). This ability of TCs to inhibit matrix metalloproteinases (MMPs) such as collagenase was found to reflect multiple direct and indirect mechanisms of action, and to be therapeutically useful in a variety of dental (e.g., adult periodontitis) and medical (e.g., arthritis, osteoporosis, cancer) diseases. The site on the TC molecule responsible for its MMP-inhibitory activity was identified which led to the development of a series of chemically modified non-antimicrobial analogs, called CMTs, which also have therapeutic potential but do not appear to induce antibiotic side-effects. Longitudinal double-blind studies on humans with adult periodontitis have demonstrated that a sub-antimicrobial dose of doxycycline (previously reported to suppress collagenase activity in the periodontal pocket) is safe and effective and has recently been approved by the FDA as an adjunct to scaling and root planing. PMID- 9972118 TI - Safety and efficacy of sub-antimicrobial-dose doxycycline therapy in patients with adult periodontitis. AB - The objectives of the studies presented here were to assess the safety and efficacy of the adjunctive administration of sub-antimicrobial-dose doxycycline (SDD) for the treatment of adult periodontitis and to confirm the optimal dosing regimen. The studies summarized included four double-blind, placebo-controlled, randomized clinical trials, conducted over a period of 9 to 12 months. Analysis of efficacy data demonstrated that adjunctive SDD treatment resulted in: (1) increases in clinical attachment levels; (2) decreases in probing pocket depths; and (3) reductions in bleeding on probing in patients with adult periodontitis. There were no significant adverse events or unwanted long-term antimicrobial effects associated with orally administered SDD. The results of these clinical trials indicate that the adjunctive use of SDD 20 mg BID is an effective and well tolerated regimen which can significantly improve several indices of periodontal health. PMID- 9972119 TI - Long-term sub-antimicrobial doxycycline (Periostat) as adjunctive management in adult periodontitis: effects on subgingival bacterial population dynamics. AB - Previous trials had indicated that various schedules of sub-antimicrobial doxycycline significantly reduced gingival crevicular fluid (GCF) collagenase activity in adult patients with periodontitis with no evidence of emergent tetracycline-resistant (Tcr) marker oral flora. The purpose of this nine-month study was to expand these observations, emphasizing newer microbial diagnostic methods. Subgingival paper point samples were obtained at baseline (BL), 3, 6, and 9 months. Four subject treatment groups in a double-blind design were evaluated by mechanical scaling and root planing (SRP) and/or 20 mg doxycycline BID (Periostat). Thirty-eight patients entered the study at baseline (BL). Dark field microscopy on 260 samples showed that morphotype distribution was independent of treatment schedule. Culture analysis of the 3 most prevalent isolates recovered showed that Streptococcus and Prevotella species accounted for approximately 85% of the 724 cultures. There did not appear to be any overgrowth or replacement by opportunistic oral flora. Of 658 susceptibility patterns evaluated by Etest, the MIC50/90 and mode MIC showed stable patterns, independent of treatment group. Our findings were different from those of previously published reports, but may be partly explained by the lack of universally standardized methods in oral microbiology and interpretive criteria for susceptibility testing. PMID- 9972120 TI - Measurement of proteinase activity in gingival crevicular fluid following periodontal therapy. PMID- 9972121 TI - Root-surface caries in rats and humans: inhibition by a non-antimicrobial property of tetracyclines. AB - The incidence of root caries has been found to increase as the population ages and as edentulism becomes less prevalent due to improved dental awareness and care, and as exposure of roots due to gingival recession has also increased in the elderly. The mechanism of root caries is thought to be mediated by both bacterial and mammalian proteases produced by plaque and the periodontal tissues, respectively. In the current study, a rat model of periodontal disease was used in which gnotobiotic rats were infected intra-orally with a periodontal pathogen (P. gingivalis). Infecting the rats with P. gingivalis increased the collagenase activity in the gingival tissue in association with severe alveolar bone loss. Treating P. gingivalis-infected rats with doxycycline or CMT-1 prevented the destruction of the periodontium by MMPs, thus preventing exposure of roots to subgingival bacterial plaque and host tissue collagenases and the subsequent development of root caries. In addition, a low-dose doxycycline (LDD, 20 mg bid, non-antimicrobial dose) for 3 months was used in humans predisposed to increased root caries as the result of heavy use of smokeless (chewing) tobacco, causing gingival recession, subgingival plaque accumulation with Gram-negative bacteria, increased gingival crevicular fluid flow (GCF), and elevated GCF collagenase. Daily administration of LDD in smokeless tobacco patients reduced the GCF collagenase and prevented the further development of root caries. PMID- 9972122 TI - The potential role of doxycycline in the treatment of osteoarthritis of the temporomandibular joint. AB - Collagenase and gelatinase are matrix metalloproteinases (MMPs) which play an important role in tissue destruction in arthritic joints. Studies have demonstrated that tetracyclines can inhibit MMPs and prevent tissue destruction independent of their antimicrobial activity. The purpose of this pilot study is to assess the potential therapeutic role of Doxycycline in patients with advanced osteoarthritis of the temporomandibular joint (TMJ). This ongoing investigation includes patients with a diagnosis of osteoarthritis of the TMJ based on clinical and diagnostic imaging findings, symptoms (localized TMJ pain, limited mobility, dysfunction) for a minimum of 36 months, and failure of previous non-surgical and surgical modalities to alleviate the symptoms. A synovial fluid sample is collected by a saline injection and aspiration technique, followed by diagnostic arthroscopy. Patients are placed on Doxycycline 50 mg BID for three months and then undergo repeat diagnostic arthroscopy and synovial fluid collection. The samples are stored at -80 degrees C. Collagenase activity is determined by a combination of SDS-polyacrylamide gel electrophoresis and fluorography and calculated based on the percentage of collagen alpha chains that are degraded into alphaA breakdown products. Three patients have completed the three-month course of Doxycycline thus far, and 5 joints with osteoarthritis have been analyzed. All patients were female (mean age = 35, mean duration of symptoms = 132 months) and had undergone previous bilateral arthroscopies. One patient had undergone unilateral arthroplasty. The mean collagenase activity showed 55% collagen lysis prior to Doxycycline treatment and 19% after three months of therapy. The mean gelatinase activity was 28% prior to Doxycycline treatment and 7% after three months of therapy. The mean interincisal opening was 33 mm initially and 41 mm after three months of Doxycycline. Subjectively, two of the three patients reported significant improvement in their overall symptoms, which they had not experienced over the previous three years. One patient did not experience any change in symptoms, in spite of a marked reduction in collagenase activity from 86.4% to 9.6%. Because of the very small numbers of patients enrolled in this pilot study so far, no statistically significant differences could be appreciated. However, the dramatic reduction in collagenase activity in these patients, with a long history of TMJ symptoms from osteoarthritis, suggests the potential promising role of Doxycycline in the management of osteoarthritis, and further investigation is warranted. PMID- 9972123 TI - Effects of tetracyclines on bone metabolism. AB - The anti-resorptive properties of tetracyclines (TCs) and their non antimicrobial, chemically modified analogues (CMTs) have enormous therapeutic potential in medicine and dentistry. Osseous destructive diseases associated with excessive mammalian collagenase (matrix metalloproteinase) activity and collagen breakdown include malignancy, arthritis, and periodontitis. However, apart from the significant antimatrix metalloproteinase effects of TCs, TCs/CMTs are also potent inhibitors of osteoclast function (i.e., anti-resorptive). Thus, TCs can affect several parameters of osteoclast function and consequently inhibit bone resorption by (1) altering intracellular calcium concentration and interacting with the putative calcium receptor; (2) decreasing ruffled border area; (3) diminishing acid production; (4) diminishing the secretion of lysosomal cysteine proteinases (cathepsins); (5) inducing cell retraction by affecting podosomes; (6) inhibiting osteoclast gelatinase activity; (7) selectively inhibiting osteoclast ontogeny or development; and (8) inducing apoptosis or programmed cell death of osteoclasts. TCs/CMTs, as anti-resorptive drugs, may act similarly to bisphosphonates and primarily affect osteoclast function. PMID- 9972124 TI - Doxycycline inhibits collagen synthesis by differentiated articular chondrocytes. AB - Doxycycline (DOX) profoundly inhibited collagen synthesis by differentiated articular chondrocytes. At 25 microM, the rate of collagen synthesis was suppressed by more than 50% without affecting cell proliferation (DNA levels) and general protein synthesis (35S-Met and 35S-Cys incorporation). Steady-state mRNA levels of type II collagen were also reduced, indicating that DOX may have an effect at the transcriptional level of type II collagen. The IC50 value of DOX to downregulate collagen synthesis (17 microM) is close to DOX levels attained in vivo (< 10 microM), and it is more than ten-fold lower than the IC50 values to inhibit the activity of most matrix metalloproteinases (MMPs). As such, these findings support the hypothesis that the reduced severity of OA observed in the dog anterior cruciate ligament model resulting from prophylactic treatment with DOX may involve mechanisms other than MMP inhibition alone. Our findings suggest that prevention of changes in the chondrocyte phenotype may be involved in the beneficial effect of doxycycline in experimental osteoarthritis, for differentiated chondrocytes in early stages of osteoarthritis exhibit elevated collagen synthesis. PMID- 9972125 TI - Effect of minocycline on osteoporosis. AB - The effect of oral minocycline on osteopenia in ovariectomized (OVX) old rats was examined in this study. Rats were divided into 4 groups: sham-operated, OVX followed by treatment with vehicle, minocycline, or 17 beta-estradiol. The treatment was initiated one day after OVX and proceeded for 8 wks. OVX reduced bone mineral density (BMD) in the whole femur and in the femoral regions that are enriched in trabecular bone. Treatment with minocycline or estrogen prevented a decrease in BMD. Femoral trabecular bone area, trabecular number, and trabecular thickness were reduced, and trabecular separation was increased by OVX. Treatment with minocycline or estrogen abolished the detrimental effects induced by OVX. OVX also reduced indices that reflect the interconnectivity of trabecular bone, and the loss of trabecular connectivity was prevented by treatment with minocycline or estrogen. Based on the levels of urinary pyridinoline, we showed that the effect of estrogen, but not minocycline, was primarily through its inhibitory effect on bone resorption. Analysis of bone turnover activity suggests that OVX increased parameters associated with bone resorption (eroded surface) and formation (osteoid surface, mineralizing surface, mineral apposition rate, and bone formation rate). Treatment with minocycline reduced bone resorption modestly and stimulated bone formation substantially. In contrast, treatment with estrogen drastically reduced parameters associated with both bone resorption and formation. We have concluded that oral minocycline can effectively prevent the decrease in BMD and trabecular bone through its dual effects on bone resorption and formation. PMID- 9972126 TI - Long-term therapy with a new chemically modified tetracycline (CMT-8) inhibits bone loss in femurs of ovariectomized rats. AB - The effect of a new non-antimicrobial analog of tetracycline (CMT-8) on bone loss in ovariectomized (OVX) rats was examined. Three-month-old female rats were ovariectomized, and one week later, were distributed into 3 groups: sham-operated non-OVX controls, vehicle-treated OVX controls, and CMT-8-treated OVX rats. After 145 days of daily CMT-8 administration, the intact femurs were dissected and examined by several histological and histomorphometric techniques. OVX significantly (p < 0.01) decreased trabecular bone volume by 53.4% in the metaphyses compared with sham-operated controls. CMT-8 therapy produced a significant (p < 0.05) inhibition of trabecular bone loss and also induced bone formation in the OVX rats. Of interest, the newly synthesized bone in the CMT treated OVX rats was found to increase the "connectivity" of the trabecular "struts" by bridging the adjacent longitudinal bone trabeculae, forming dense, plate-like bone trabeculae. These results strongly suggest that long-term CMT-8 therapy effectively inhibits bone loss after OVX, not only by inhibiting bone resorption but also by inducing new bone formation in the trabecular areas of long bones. PMID- 9972127 TI - Effect of an inhibitor of matrix metalloproteinases on spontaneous osteoarthritis in guinea pigs. AB - Recently discovered chemically modified tetracyclines have been found to be effective inhibitors of matrix metalloproteinase (MMP)-mediated connective tissue destruction in a variety of pathologic processes, including rheumatoid arthritis and osteoarthritis (OA). Since the histologic techniques used in our laboratory have been validated in Hartley guinea pigs, which have a high incidence of OA like changes in the proximal tibia, we have used two tetracyclines which have potent inhibitory capacity against various MMPs, doxycycline (Dox) and a compound known as chemically modified tetracyclines (CMT-7). These were given by mouth to a group of guinea pigs for 4 to 8 months, and we assessed the effect of the compound on morphologic and biochemical aspects of OA. We found that prophylactic CMT-7 given orally decreases OA changes in the knee joints both in vitro and in vivo in the guinea pig OA model. Cartilage fibrillation and destruction, in addition to subchondral bone sclerosis and cyst formation, were all decreased in the central compartment of the medial condyle, which is most affected by OA compared with controls. Also collagen, hyaluronan and proteoglycancontent in cartilage was higher in the CMT-7 treated group compared with controls. In contrast, OA changes were not decreased in the Dox group. Our results confirm that various tetracyclines have reduced the severity of OA in animal models, indicating the therapeutic potential of this class of compounds in the future. PMID- 9972128 TI - Tetracycline-based MMP inhibitors can prevent fibroblast-mediated collagen gel contraction in vitro. AB - Collagen gels in vitro can be contracted by fibroblasts. The role of matrix metalloproteinases (MMPs) in the contraction of collagen lattices by human neonatal foreskin fibroblasts (HuFFs) was investigated in tissue culture media supplemented by various doses of known gelatinase inhibitors. Fluorescent assays with model gelatinase substrates and media conditioned by fibroblasts apparently confirmed the ability of chemically modified tetracyclines (CMTs) to act as inhibitors of MMP2, and zymography demonstrated that this was the major cell derived MMP activity. There were no observable effects on the rate of contraction of attached FPCLs containing 6 x 10(4) HuFFs (passages 18-25) with either CMT-5 or CMT-2 at all concentrations tested (0-100 micrograms/mL). However, at greater than 20 micrograms/mL doxycycline and greater than 5 micrograms/mL CMT-3, FPCL contraction was completely abolished. Quantitative assessment of cell viability by means of the MTT assay in monolayer and qualitatively within the FPCLs with CalceinAM suggested that differences were not due to cytotoxic effects. Seeding FPCLs with lower-passage fibroblasts produced identical trends. These results may implicate the involvement of MMPs in the process of gel contraction, although tetracyclines have effects additional to their ability to inhibit MMPs directly. PMID- 9972129 TI - Effects of doxycycline on cancer cells in vitro and in vivo. PMID- 9972130 TI - Potential application of a chemically modified non-antimicrobial tetracycline (CMT-3) against metastatic prostate cancer. PMID- 9972131 TI - Application of chemically modified tetracyclines (CMTs) in experimental models of cancer and arthritis. PMID- 9972132 TI - Minocycline inhibits in vitro invasion and experimental pulmonary metastasis of mouse renal adenocarcinoma. PMID- 9972133 TI - Inhibition of MMP synthesis by doxycycline and chemically modified tetracyclines (CMTs) in human endothelial cells. AB - Doxycycline is a commonly used broad-spectrum antibiotic. Recently, it has been shown that it also inhibits the activity of mammalian collagenases and gelatinases, an activity unrelated to its antimicrobial efficacy. In this study, we show that doxycycline not only inhibits MMP-8 and MMP-9 (gelatinase B) activity, but also the synthesis of MMPs in human endothelial cells. Doxycycline (50 microM) completely inhibited the phorbol-12-myristate-13-acetate (PMA) mediated induction of MMP-8 and MMP-9, as measured by Western blotting and gelatin zymography, respectively. The inhibition was also observed at the mRNA level. No effect was observed on the expression of MMP-2 and of the MMP inhibitors TIMP-1 and TIMP-2. Chemically modified tetracyclines (CMTs) showed an inhibition similar to that of doxycycline, albeit less efficient. These observations demonstrate that endothelial cells display a specific regulation of MMPs, which may have implications for the pharmaceutical interaction in angiogenesis and angiogenesis-related diseases. PMID- 9972134 TI - Effects of tetracyclines on the pathologic activity of endotoxin: in vitro and in vivo studies. AB - Lipopolysaccharide (LPS) is considered to be one of the major virulence factors of Gram-negative bacteria. Recently, tetracyclines (TTCs) were found to prevent the patho-physiological changes associated with LPS in vivo and the secretion of inflammatory mediators in vitro. However, the mechanism by which TTCs prevents LPS-induced pathology in vivo is still unclear. In order to shed light on that problem, we carried out in vitro and in vivo experiments. TTC inhibited the secretion of nitric oxide (NO) and TNF alpha from LPS-stimulated macrophages and inhibited macrophage-induced thymocyte proliferation. However, TTC inhibited NO secretion with use of concentrations five-fold lower than those that inhibited TNF alpha secretion and thymocyte proliferation. The secretion of NO was inhibited by the addition of TTC to the cultures up to 6 hrs post-LPS stimulation. TTC inhibition of LPS-induced NO secretion was not reversed by the addition of recombinant TNF alpha, and TTC inhibition of LPS-induced TNF alpha secretion was not reversed by the addition of NO donor. These results suggest that the inhibition of TNF alpha by TTC is not the result of the inhibition of LPS-induced NO secretion or vice versa. In vivo experiments had shown that TTC prevented mortality in LPS-treated mice, but not in mice pre-sensitized with galactosamine prior to the LPS challenge. These results suggest that TTC activity in vivo is due not to the suppression of synthesis of inflammatory mediators but rather to the induction of acute phase-like response, which antagonizes the LPS induced activity. PMID- 9972135 TI - Effects of chemically modified tetracyclines on iNOS in mesangial cells: impact on experimental glomerulonephritis. PMID- 9972136 TI - Modulation of nitric oxide production by tetracyclines and chemically modified tetracyclines. AB - Chemically modified tetracyclines (CMTs) dose-dependently decreased inducible nitric oxide synthase (iNOS) and, consequently, nitric oxide (NO) formation by the lipopolysaccharide (LPS)-stimulated J774 line. The inhibitory effect was due to a specific reduction in the iNOS protein content in the cells, as attested by Western blot analysis and by the inhibition of iNOS mRNA accumulation. Furthermore, CMTs cause a dose-dependent increase in cell death in the J774 line mediated by the NO-independent apoptotic mechanism. PMID- 9972137 TI - The effects of chemically modified tetracyclines (CMTs) on human keratinocyte proliferation and migration. AB - Chemically modified non-antimicrobial tetracycline derivatives and other low molecular-weight synthetic matrix metalloproteinase (MMP) inhibitors inhibited keratinocyte migration. Since 72-kDa gelatinase-A (MMP-2) was the major gelatinase in our culture conditions, the results suggest that this MMP may be important in the regulation of keratinocyte mobility. On the other hand, we measured only gelatinase activities (MMP-2 and -9) present in culture medium, and therefore the results do not reveal how the inhibitors affect other MMPs as well as MMP levels close to the cell membranes. Overall, CMTs were found to be efficient in the inhibition of keratinocyte migration. PMID- 9972138 TI - Tetracycline derivatives induce apoptosis selectively in cultured monocytes and macrophages but not in mesenchymal cells. AB - Evidence for a non-antibiotic activity displayed by certain tetracycline derivatives is presented. This activity is a selective cytotoxicity toward cells of the monocytic lineage (the human histiocytic lymphoma U937 cell line and the mouse macrophage line RAW264) but not toward various cells of a mesenchymal lineage (including primary ovine articular chondrocytes and meniscal cells, murine calvarial osteoblasts and MG-63 osteosarcoma cells, and primary human neonatal foreskin fibroblasts). Cells were incubated with various chemically modified tetracycline derivatives (CMTs) or doxycycline for 24 hrs at a range of concentrations between zero and 50 micrograms/mL in both serum-containing and serum-free culture conditions. Assessment of cell viability by means of the MTT assay demonstrated a potent dose-dependent cytotoxic effect induced by compound CMT-3 and a less potent effect induced by doxycycline, but no apparent cytotoxic effect in the presence of either CMT-2 or CMT-5. Cytospin preparations analyzed by the labeling of DNA fragments indicated the same trends and suggested that cell death was via an apoptotic mechanism. The cytotoxic potency of these tetracyclines toward cells of the monocytic lineage could be diminished but not abolished by either the presence of 10% fetal calf serum within the culture medium, or pre-treatment with phorbol esters to promote a more macrophage-like phenotype. These data provide evidence that, in addition to well-characterized antibiotic and MMP-inhibitory characteristics, tetracyclines may function by a novel mechanism to induce selective apoptosis. PMID- 9972139 TI - Topically applied CMT-2 enhances wound healing in streptozotocin diabetic rat skin. AB - Delayed wound healing is one of the complications of diabetes mellitus, exhibited by increased wound collagenase and decreased granulation tissues. The current study compared wound healing in normal and diabetic rats, and the effects of topically applied 1% or 3% concentrations of chemically modified tetracycline-2 (CMT-2) on 6-mm circular full-thickness skin wounds healed by secondary intention. On day 7 after wounding, tissues were removed for biochemical analysis and histology. The wound granulation tissue hydroxyproline was less in the untreated diabetic rat with increased collagenase and gelatinase. Treating the diabetic rat wounds with 3% CMT-2 increased the wound hydroxyproline and decreased activities of gelatinase and collagenase. There was a delay in wound filling by granulation tissue in diabetic rats. In CMT-2-treated diabetic rats, the volume of granulation tissue was greater than that in untreated diabetic rats. CMT-2 appears to normalize wound healing in diabetic rats and may be a valuable adjunct in the treatment of chronic wounds. PMID- 9972140 TI - How do tetracyclines work? AB - This paper is a summary of a panel discussion by the following panelists: L. Golub, J. te Koppele, G. Nieman, M. Nelson, R. Ashley, T. Sorsa, and S. Simon. The panel discussed the mechanisms by which the tetracyclines and their non antimicrobial counterparts may provide therapeutic efficacy in a variety of chronic and acute diseases. PMID- 9972141 TI - Tetracyclines inhibit protein glycation in experimental diabetes. AB - Glycation of proteins, which is accelerated in the diabetic state, has been implicated in many of the long-term complications of diabetes. This process can be inhibited by members of the tetracycline family of compounds. This novel finding is supported by studies conducted on drug (streptozotocin)induced Type I and genetic (ZDF/Gmi-fa/fa) Type II diabetic rats. These animals were orally gavaged daily with 5 mg of doxycycline and a variety of non-antimicrobial chemically modified tetracycline derivatives for time periods of 3 weeks to 11 months, while control untreated diabetic and nondiabetic animals were gavaged with vehicle alone (2% CMC). Blood and tissue samples were collected and analyzed for glucose and glycated proteins. None of the treatments had any effect on the severity of hyperglycemia or the intracellular glycation of hemoglobin of either Type I or II diabetic animals. However, the tetracycline analogues did affect the extracellular glycation of several proteins such as those found in the serum as well as skin collagen. In the Type II (ZDF) animals, initial mortality (3-5 months) was seen only in the doxycycline-treated animals, associated with infection by tetracycline-resistant micro-organisms, which was eventually surpassed by mortality rates in the untreated diabetics (6-9 months). CMT treatment not only decreased mortality but also increased longevity in the Type II diabetic animals, most likely by preventing the development of a number of long-term complications of uncontrolled diabetes, including glycation of proteins, that eventually lead to the demise of untreated diabetic animals. PMID- 9972142 TI - Therapeutic potential of tetracycline derivatives to suppress the growth of abdominal aortic aneurysms. AB - Abdominal aortic aneurysms (AAA) represent a potentially lethal disorder associated with aging and atherosclerosis. Although current management of AAA is predicted on early detection and elective surgical repair, routine screening for AAA is infrequent, because most AAA are too small to warrant repair when first detected and because there are no therapeutic approaches proven to suppress aneurysm expansion. Basic research on this problem suggests that chronic inflammation and increased local production of elastin-degrading proteinases play prominent roles in the process of aneurysmal degeneration. Members of the matrix metalloproteinases (MMP) family appear to be the most prominent elastases produced in human AAA, suggesting that unique therapeutic targets might exist for aneurysm disease. Studies using a representative animal model for AAA support this view, providing a means for further development of pharmacological approaches to suppress aneurysm expansion. Indeed, recent work indicates that tetracycline derivatives have the potential to interrupt the progressive connective tissue destruction that occurs in AAA, by virtue of their non antimicrobial properties as MMP inhibitors, and they do so at clinically achievable dose schedules. These findings support the view that MMPs are potentially important pharmacotherapeutic targets in AAA and, moreover, that tetracyclines might be useful in suppressing aneurysm expansion in vivo. Because tetracycline derivatives offer a number of distinct advantages as MMP inhibitors for patients with small AAA, prospective clinical trials of this novel therapeutic strategy can be anticipated in the near future. PMID- 9972143 TI - Potential application of low-dose doxycycline to treat periodontitis in post menopausal women. AB - The purpose of this paper is two-fold: (1) to review the evidence that osteoporosis and post-menopausal estrogen deficiency are associated with progressive alveolar bone loss and an elevated risk of tooth loss; and (2) to propose the use of tetracyclines, specifically low-dose doxycycline (LDD) (and, perhaps in the future, the chemically modified tetracyclines), to mitigate alveolar bone loss in post-menopausal osteoporotic/osteopenic women. Design concepts for a randomized clinical trial to study the effects of LDD on progressive alveolar bone loss in this patient population are reviewed. Since osteoporosis affects over 20 million people in the United States, progressive alveolar bone loss in this patient group represents a potentially significant public health problem unique from common adult periodontitis. Stopping progressive alveolar bone loss is essential to prevent both tooth loss and micro architectural deterioration of alveolar bone. PMID- 9972144 TI - Observer variation in the assessment of resin composite. AB - OBJECTIVES: The aim of this study was to compare the type of information obtained from log-linear modelling vs Cohen's kappa statistics on observer variation in the assessment of marginal adaptation in composite inlays and amalgam restorations. METHODS: Marginal adaptation of Class II resin composite inlays and amalgam restorations was clinically assessed by two observers, four years after placement. Each of 52 patients received 4 different restorations, three composite (Herculite XR, Clearfil CR Inlay and Visiomolar) inlays and one Tytin restoration. The results were evaluated by Cohens Kappa statistics and log-linear modelling. RESULTS: The overall Cohen's kappa was 0.45, ranging from poor to good for the four materials. Log-linear modelling confirmed that the observers agreed beyond chance but this agreement depended on the performance of the material. Marginal adaptation of Visiomolar (ESPE) inlays was somewhat inferior compared to the other materials. The assessment of Clearfil CR (Kuraray) inlay was difficult using this clinical evaluation procedure. SIGNIFICANCE: Using log-linear modelling it is possible to look at observer agreement and material performance at the same time. This combined approach is important because agreement may depend on material performance. PMID- 9972145 TI - Effects of HEMA on water evaporation from water-HEMA mixtures. AB - OBJECTIVES: The aims of this research were: (1) to determine the relative rates of evaporation of water and HEMA, and (2) to determine the effects of increasing concentrations of HEMA on the rate of evaporation of water from water and HEMA mixtures. METHODS: Ten microliters of each solution (100% H2O, 75% H2O-25% HEMA, 50% H2O-50% HEMA, 25% HEMA, 100% HEMA) were placed on the pan of a thermogravimetric analysis instrument held at 37 degrees C. The rate of spontaneous weight loss was measured as a function of time and relative humidity (RH) and compared statistically using ANOVA and Scheffe F test. RESULTS: The rate of evaporation of pure water was 32-fold higher than that of 100% HEMA. Addition of HEMA to water lowered the rate of evaporation of water from the water-HEMA mixtures in a manner that was proportional to its effect on lowering the vapor pressure of water (p < 0.05 comparing 50% HEMA with 75% HEMA). The rate of evaporation of water from water-HEMA mixtures was higher (p < 0.05) when the ambient gas was at 0% RH than when it was at 51% RH. SIGNIFICANCE: The results indicate that as water evaporates from water-HEMA mixtures, the concentration of HEMA rises because it is relatively non-volatile. This rise in HEMA concentration lowers the vapor pressure of water making it more difficult to remove the last amounts of water. This residual water may interfere with polymerization of adhesive monomers, thereby lowering the quality of the hybrid layer. PMID- 9972146 TI - Cyclic contact fatigue of a silver alternative to amalgam. AB - OBJECTIVE: To purpose of this study was to compare the cyclic contact fatigue resistance of a novel mercury-free silver direct filling material to that of a dental amalgam (Dispersalloy). METHODS: The silver specimens were made by pressing a precipitated powder at room temperature with a pressure of 150 MPa, which can be achieved in clinical hand-consolidation. To simulate clinical contact of restorations against enamel cusps, a cyclic contact fatigue methodology was employed. A spherical indenter was used to repeatedly indent the specimen, while the accumulation of deformation and damage was examined as a function of the number of cycles up to 5 x 10(5). Student's t test, analysis of variance (ANOVA) and Duncan's multiple range test were used to compare the specimen groups for significant differences in flexural strength, indentation impression diameter, and hardness. A type I error of alpha = 0.05 was considered as significant. Subsurface damage was examined by using a bonded-interface technique. RESULTS: As a result of cyclic indentation, microcracks were produced in the amalgam, but no cracks were found in the silver filling material. At fewer numbers of cycles, indentation produced larger impressions in silver (e.g., diameter = [450 +/- 31] microns at 10(2) cycles) than in amalgam ([145 +/- 20] microns) due to a lower hardness of the former. However, with increasing number of cycles, damage accumulated more rapidly in the amalgam, while the silver beneficially work-hardened in repeated indentations. At 5 x 10(5) cycles, the difference in impression diameter between silver and amalgam ([582 +/- 20] microns vs. [568 +/- 42] microns) become insignificant (p > 0.1, Student's t test). SIGNIFICANCE: The mercury-free silver direct filling material is more resistant to microcracking and to cyclic contact fatigue than amalgam, and the indentation impression sizes in the consolidated silver and dental amalgam are not statistically different at large numbers of cycles. PMID- 9972147 TI - Surface energy characteristics of adhesive monomers. AB - OBJECTIVES: The aim of the investigation was to determine the surface free-energy components of potentially adhesive monomer mixtures. METHODS: Four liquids with known components of surface free-energy were used as reference. Small drops of the liquids were placed on the polished surfaces of four types of solid (metal, porcelain, resin composite and hydrocarbon), and the contact angles were measured. By means of the fundamental equations for wetting, the three components of the surface free-energy of the four solids were calculated. Small drops of various monomeric mixtures were then placed on the four solid surfaces, and on the basis of the previously calculated components of surface free-energy of the solids, the surface energy characteristics of the monomeric mixtures were determined. The relationships between contact angles and composition, and between surface tension and composition, were studied by regression analyses. Comparisons between values were carried out by means of Neuman-Keuls' multiple range test at a level of statistical significance of p = 0.05. RESULTS: Statistically significant differences between the monomeric mixtures as regards the wetting of the four solids were observed. These differences reflected differences in the acid or base component of the surface free-energy of the monomers. In particular, monomeric mixtures containing HEMA, MAN or 4-META exhibited a significant acid component of the surface free-energy. SIGNIFICANCE: Knowledge of the surface free energy components of monomers throws light on the mechanisms associated with the adhesion of resin composites, including resin cements. A better understanding of the interfacial interactions may act as guide in a research aimed at developing resin materials of increased adhesion to metal, porcelain or resin composite. PMID- 9972148 TI - Effect of filler porosity on the abrasion resistance of nanoporous silica gel/polymer composites. AB - OBJECTIVES: This laboratory study was designed to investigate the effect of controlled nanoporosity on the wear resistance of polymeric composites reinforced with silica gel powders and to determine the mechanisms controlling the abrasive wear properties of these unique nanostructured materials. METHODS: Silica gels were prepared by hydrolysis and condensation of tetraethylorthosilicate (TEOS) using four different catalysts to modify the porous structure of the resulting polysilicate silanation, an organic monomer (TEGDMA) containing various initiators was introduced into the gel powders to form a paste. The various pastes were then polymerized inside a glass mold. A pin-on-disk apparatus was then used to record the specimen length and number of revolutions. Abrasive wear rates were determined by regression analysis and statistical differences were determined by analysis of variance and multiple comparisons. BET was used to characterize the filler pore structure and scanning electron microscopy was used used to visually examine the abraded surfaces. RESULTS: Significant differences (p < 0.05) in the wear rates of the experimental composites were noted. Within the range of filler porosities examined, wear resistance was found to be linearly dependent (R2 = 0.983) on filler pore volume. The wear rates decreased with increasing filler porosity. HCl-catalyzed gels having low porosity produced composites having relatively limited abrasion resistance. In contrast, high porosity HF-catalyzed gels produced more wear-resistant composites. The abrasive wear resistance of these nanocomposites was not significantly affected by the level of silane coupling used in these experiments. SEM evaluation suggested that better wear resistance was associated with fine-scale plastic deformation of the wear surface and the absence of filler particle pullout. SIGNIFICANCE: Porous particles prepared via sol-gel show some promise as fillers that improve the wear resistance of photopolymerized resins. The wear resistance of the fillers appears to be directly related to nanoporous structure of the gel particles. Unlike conventional dental composites, these materials rely primarily on nanomechanical coupling for improved wear resistance. This new principle should benefit subsequent investigations. PMID- 9972149 TI - Design of prosthetic cantilever bridgework supported by osseointegrated implants using the finite element method. AB - OBJECTIVES: The aim of the present work was to establish a design procedure for fixed metal prostheses supported by osseointegrated implants in order to prevent permanent deformation and hence failure following loading. Previously, the cantilever cross-sectional shape in the buccal lingual plane has been based on clinical experience and subjectivity. METHODS: This work has relied on the use of linear elastic finite element analysis in order to generate a maximum effective stress at which permanent deformation commences on loading. A number of different cross-sectional shapes were investigated, both of conventional design as well as new innovative possibilities. Both straight and curved cantilever beams 26 mm long were examined. RESULTS: The design failure chosen was based on a von Mises plastic collapse principle by comparing the calculated effective stresses with the yield stress of the metal in simple tension. It was found that the "L" shaped design was more rigid than other designs for a given mass, while a framework based on an open "I" section offers good possibilities particularly when used as curved shapes. SIGNIFICANCE: Assuming a failure criterion based on the von Mises principle, then "L" shaped Co/Cr or stainless steel frameworks, typically 26 mm of cantilever span, undergo permanent deformation at end loadings between 130 and 140 N depending on section curvature. Since it is known biting loads can exceed these values, good design is critical if such failures are to be avoided. PMID- 9972150 TI - Microtensile bond strength testing and failure analysis of two dentin adhesives. AB - OBJECTIVES: This investigation was conducted to determine the tensile bond strength of two dental adhesive using a recently introduced "microtensile" bond strength testing design and to verify the failure mode for each test specimen with scanning electron microscopy (SEM). METHODS: Extracted human molars were mounted in stone and the enamel was removed the occlusal surface perpendicular to the long axis of the tooth. A composite resin crown was formed on this flat dentin surface utilizing each dental adhesive system according to manufacturer's instructions. Twenty-four hours later the bonded test specimens were sectioned perpendicular to the adhesive joint, producing six to seven thin slabs per tooth. These dentin/adhesive/composite resin slabs were sectioned free from the stone block and mounted into custom Plexiglas fixtures for trimming and subsequent tensile bond strength testing at 7 d post-bonding. The bond strength of the two adhesives was statistically compared with the t test. The broken specimens were examined with SEM to determine the fracture location or failure mode. Failures for each adhesive system were categorized as either interfacial (joint or mixed) or substrate (dentin and composite) and evaluated by Fisher's exact test. RESULTS: The tensile bond strength and failure modes of All-Bond 2 (Bisco) and Optibond FL (Kerr) were not significantly different. Sixty per cent (12/20) of fractures involving All Bond 2 occurred at the interface, with seven being entirely maintained within the joint, whereas Optibond FL had 35% (7/20) involving some portion of the interface, two totally within the joint. Cohesive fractures of either dentin or composite accounted for 55% of the total failure modes (21/40). The remaining dentin thickness did not affect the measured tensile bond strength. SIGNIFICANCE: This versatile new method permits multiple measurements from a single tooth or small surface areas within a restoration but careful interpretation of the failure mode is required to prevent inappropriate conclusions about the utility of the test. PMID- 9972151 TI - Influence of UEDMA BisGMA and TEGDMA on selected mechanical properties of experimental resin composites. AB - OBJECTIVES: This study was conducted to determine the effect of UEDMA, BisGMA and TEGDMA on selected mechanical properties of experimental resin composites. METHODS: Thirty monomer mixtures of TEGDMA and BisGMA and/or UEDMA were produced. Five base monomer mixtures had the following molar relationships between TEGDMA and BisGMA: 30:70, 40:60, 50:50, 60:40 and 70:30. Monomer mixtures were then produced in which BisGMA was successively substituted by UEDMA, 10 mol% at a time. The resins were made light-curing and loaded with filler. Diametral tensile strength, flexural strength and modulus of elasticity were determined on 1 week old specimens. The results were analyzed by ANOVA and by response surface methodology. RESULTS: The diametral tensile strength of the resin composites varied between 52 and 59 MPa, the flexural strength between 137 and 167 MPa, and the modulus of elasticity between 8.0 and 11.1 GPa. The statistical analyses showed that substitution of BisGMA or TEGDMA by UEDMA resulted in an increase in tensile and flexural strength, and that substitution of BisGMA by TEGDMA increased tensile, but reduced flexural strength. Further, it was found that, for a given content of UEDMA, variations in the ratio BisGMA/TEGDMA gave rise to a maximum in modulus of elasticity. The size of this maximum in modulus decreased with increasing content of UEDMA. SIGNIFICANCE: Varying the relative amounts of UEDMA, BisGMA and TEGDMA has a significant effect on the mechanical properties of the resin composition. Thus, by selecting specific combinations of these components, it may be possible to design composites with properties that are tailor made to specific applications. PMID- 9972152 TI - Acid-base reaction and fluoride release profiles in visible light-cured polyacid modified composite restoratives (compomers). AB - OBJECTIVE: The aim of the study was to evaluate the extent of the acid-base reaction and F- release in Compoglass (Vivadent) and Dyract (Dentsply/DeTrey) restoratives. METHODS: For evaluation of the extent of the acid-base reaction, two groups of three specimens (7 mm x 5 mm x 1 mm) were prepared for each material. The first group was immersed in distilled water, while the second was kept in dark and dry conditions. Micro-MIR FTIR spectroscopy was used to determine the extent of the acid-base reaction on directly irradiated material surfaces immediately after irradiation and following water storage for 30 min, 3 d, 1, 2, 4, 8 and 12 wks. The in-depth extent of the acid-base reaction of the specimens stored in water for 4 weeks was studied by sequential spectra acquisition after removal of the uppermost 20, 70, 100, 240 and 400 microns layer by controlled grinding and 1 wk re-immersion in water of the 400 microns reduced specimens. For the F- release measurements, five disk-shaped specimens (10 mm x 1.5 mm) were prepared from each material and stored in distilled water. The amount of F- released for the storage periods reported above was measured using an ionometer with an F- electrode. Statistical analysis was performed by ANOVA, Scheffe's test and regression analysis. RESULTS: Storage in water promoted the development of an acid-base reaction on directly irradiated surfaces which reached a saturation point after 4 weeks. Depth profiling of the 4 wk immersed specimens revealed high salt concentration at the uppermost 100 microns layer. Re immersion in water for 1 week of the 400 microns reduced specimens increased the salt concentration again at the uppermost region. Statistically significant differences were found in the acid-base rates and the in-depth salt yields between the materials (p < 0.05). The fluoride release after a 1 week initial "bursting" period was stabilized below 2 mg l-1 (p > 0.05) in both products. No positive correlation was found between acid-base reaction and fluoride release. SIGNIFICANCE: The development of a carboxylate-rich surface layer on polyacid modified composite restoratives after water storage may explain their lower wear resistance compared with resin composites. The dynamic nature of these surfaces may provide several advantages regarding their interaction potential with hard dental tissues and their anticariogenic properties, but also some disadvantages concerning the quality of the surface texture obtained. PMID- 9972153 TI - Bonding to zirconia ceramic: adhesion methods and their durability. AB - OBJECTIVES: Resin bonding to yttrium-oxide--partially-stabilized zirconia ceramic (YPSZ) cannot be established by standard methods that are utilized for conventional silica-based dental ceramics. It was our hypothesis that adhesive bonding methods suitable for glass-infiltrated alumina ceramic can also be used to bond successfully to YPSZ. To prove this hypothesis, bonding methods suitable for alumina ceramic were used on YPSZ and the tensile bond strength and their durability evaluated in vitro. METHODS: Plexiglass tubes filled with resin composite were bonded to YPSZ discs following various adhesion protocols. Groups of 16 samples were bonded using seven different bonding methods. Subgroups of eight bonded samples were tested for tensile strength following storage in distilled water (37 degrees C) for either 3 or 150 days. In addition, the 150 day samples were thermal cycled 37,500 times as a method to stress the bond interface. The statistical analysis was made with the Kruskal-Wallis test followed by multiple pair-wise comparisons of the groups using the Wilcoxon rank sum test. RESULTS: Sandblasting alone, the additional use of a silane or acrylizing resulted in an initial bond of a conventional BisGMA resin composite to YPSZ which failed spontaneously over storage time. The use of the BisGMA resin composite after tribochemical silica coating of YPSZ and the use of a polyacid modified resin composite after sandblasting of YPSZ resulted in an initial bond which decreased significantly over storage time (p = 0.05). A durable resin bond to YPSZ was achieved only after sandblasting the ceramic and using one of two resin composites containing a special phosphate monomer. SIGNIFICANCE: A durable bond to YPSZ was achieved only by using resin composites with a special adhesive monomer. Therefore, the hypothesis of the study was partially proved as a durable bond to alumina ceramic is achieved with the same resin composites. However, it was partially disproved as tribochemical silica coating of YPSZ did not result in a durable resin bond as it does on glass-infiltrated alumina ceramic. PMID- 9972154 TI - Magnetron sputtered tin coatings on unbiased ceramic substrates. AB - OBJECTIVES: The aim of this work was to study the application of tin oxide coatings on alumina, with a view to developing improved bonding for high-alumina dental ceramics. METHODS: By use of a magnetron sputtering technique, alumina was coated with tin which was subsequently oxidized, and the bond strength of coated surfaces to a resin-based dental cement was measured in tension. Tensile bond strength data were assessed for their degree of skewness and the homogeneity of the residual variances with a view to applying appropriate transformations prior to performing ANOVA with subsequent Tukey's analysis as necessary. The color of coatings, as a function of the amount of oxidation of the surface, was noted. Coatings were characterized by SEM and EDAX. It has been found possible to produce esthetic tin oxide coatings on alumina using a simplified magnetron sputtering apparatus in conjunction with post-deposition oxidation. RESULTS: Although mean tensile bond strength (TBS) values in excess of 15 MPa were recorded for a number of groups, no causal relationship was found between coating time and mean TBS. SIGNIFICANCE: The need exists for improved bonding of alumina based ceramics; further development of a magnetron sputtering technique may provide the means for achieving this. PMID- 9972155 TI - Role of microstructure on contact damage and strength degradation of micaceous glass-ceramics. AB - OBJECTIVES: This study examines the hypothesis that microstructure plays a critical role in the accumulation of strength-degrading damage in dental ceramics. A series of micaceous glass-ceramics crystallized from a common glass composition, using heat treatments to increase the diameter and aspect ratio of mica platelets, is used as a model ceramic system. METHODS: Damage modes are investigated by Hertzian contact testing. Four-point bend tests on indented specimens quantify the influence of single-cycle and multi-cycle damage on strength. RESULTS: Two competing damage modes are observed: fracture, by tensile induced cone cracking at the macroscopic level; and quasi-plastic deformation, by shear-induced yield at the microscopic level. The quasi-plastic mode becomes more dominant as the microstructures become coarser and more elongate. Bend tests show severe strength losses in the finer grain structures where cone cracking dominates, but relatively small losses in the coarser grain structures where quasi-plasticity dominates. Whereas natural strengths decline with increasing crystallization temperature, the strengths after indentation damage attain a maximum at intermediate crystallization temperatures. Multiple-cycle contact loading reduces strengths even further, and at relatively low indentation loads, indicating susceptibility to fatigue. Finite element modelling is carried out to evaluate the stress components that drive the damage modes. SIGNIFICANCE: Microstructure is confirmed to be a controlling factor in determining the nature and degree of strength-impairing damage accumulation in dental ceramics. The Hertzian test provides a means of characterizing such damage in the context of clinical function. PMID- 9972156 TI - A retrospective evaluation of patients with uncomplicated crown fractures and luxation injuries. AB - This paper is a review of the clinical findings from my thesis "Pulp survival and hard tissue formation subsequent to dental trauma". Traumatic injuries in children and adolescents are a common problem, and the prevalence of such injuries has increased over the last 10-20 years. The purpose of the present investigations was to evaluate the long-term results following uncomplicated crown fractures and luxations involving subsequent pulp canal obliteration. A total of 241 patients with 545 injured teeth were available for clinical examination, of whom 102 answered a questionnaire and were interviewed before oral examination. In addition, 82 permanent incisors presenting with pulp canal obliteration were followed for a period of 7 to 22 years (mean 16 years). The findings showed little pulpal response to crown fracture and subsequent restorative procedures as long as there was no concomitant periodontal injury (15 year follow-up). Approximately every fourth resin composite filling was rated as unacceptable at clinical examination. The interview showed that half of the individuals were dissatisfied with the color and/or anatomic form of the composite restoration. Pulp canal obliteration was found in all luxation categories, and 69% of the teeth demonstrated yellow crown discoloration. According to the survival curve the 20-year pulp survival rate diagnosed radiographically was 84%. Although the risk of pulp necrosis increased with time, routine endodontic intervention of teeth with ongoing pulp canal obliteration of the root canal did not seem justified. PMID- 9972158 TI - An in vitro comparison of thermoplasticised gutta-percha obturation techniques with cold lateral condensation. AB - This study compared the apical sealing ability, obturation time and extrusion of gutta-percha and sealer when root canals were obturated using either cold lateral condensation or one of the three methods using thermoplasticised gutta-percha (Alpha Seal, Thermafil or JS Quick Fill) in vitro. One hundred and thirty-one root canals from 78 extracted human teeth were used; 116 canals were divided into five groups so that they were balanced with respect to prepared canal anatomy, and the remaining 15 canals were used as positive and negative controls. The canals in the first four groups were prepared with hand files using the step-down technique to a standard apical size and flare. The last group was prepared using engine-driven rotary nickel-titanium files (McSpadden) to a similar apical size and flare. One of the four obturating techniques was used to fill the canals in each of the first four groups. The fifth group was obturated using the Alpha Seal technique. The roots were immersed in india ink, demineralised and rendered transparent to assess the extent of maximum lincar dye penetration. The Alpha Seal groups had the highest number of specimens without any leakage. There was a significant difference in the proportions of specimens that did not leak when the Alpha Seal (P < 0.01) and cold lateral condensation groups (P < 0.05) were compared with JS Quick Fill. Cold lateral condensation had a higher proportion of specimens with leakage in canals with curvature greater than 20 degrees than in canals with curvatures less than 20 degrees (P < 0.05). The curvature of canals had no effect on the sealing ability of the other techniques. The method of canal preparation had no effect on the sealing ability of Alpha Seal. Alpha Seal, Thermafil and JS Quick Fill were significantly quicker to perform than cold lateral condensation. PMID- 9972157 TI - Histological evaluation of the response of apical tissues to glass ionomer and zinc oxide-eugenol based sealers in dog teeth after root canal treatment. AB - The object of the study was to compare two commercial root canal sealers: Ketac Endo (a glass ionomer cement) and Fill Canal (a zinc oxide-eugenol cement). A total of 34 root canals from dog premolars with vital pulps were used. After instrumentation, the root canals were sealed with Ketac-Endo and Fill Canal cements using gutta-percha and a lateral condensation technique. After 270 days the animals were sacrificed with an anesthetic overdose and the maxillae and mandibles were removed and fixed in formalin for 48 h. After routine histological processing the sections were stained with hematoxylin-eosin and Mallory trichrome stains. Microscopic analysis revealed that Ketac-Endo cement presented better results than Fill Canal cement. PMID- 9972159 TI - Effect of Er:YAG laser treatment on the root canal walls of human teeth: an SEM study. AB - The purposes of the study were to observe the morphological changes on root canal walls after instrumentation and irrigation, and assess the efficacy of conventional cleansing procedures and the effectiveness of Er:YAG laser in removing debris and smear layer from the root canal walls. Thirty-six endodontically treated human mandibular incisor teeth with single root canals were bisected longitudinally and divided into three groups of 12 teeth. Group 1 (G1) was left unlased as a control. The teeth of group 2 (G2 and group 3 (G3) were irradiated by Er:YAG laser (laser parameters were set at 1 W, 100 mJ/pulse and 10 Hz) for 3 s and 5 s. The teeth were prepared for scanning electron microscope study. Control specimens showed debris and heavy smear layer obscuring the dentinal tubules at all levels in the canals. The root canal walls irradiated by Er:YAG laser were free of debris, with an evaporated smear layer and open dentinal tubules. These results suggested that Er:YAG laser irradiation had an efficient cleaning effect on the prepared root canal walls. PMID- 9972160 TI - A study of replanted permanent teeth in different age groups. AB - The purpose of this study was to evaluate the benefits of replanting avulsed permanent teeth in different age groups. Of the 112 replanted teeth, 103 could be examined after 2.5 years on average. The teeth were divided into three groups: immature teeth (group A), mature teeth in children and adolescents (group B), and mature teeth in adults (group C). Concomitant injuries did not differ statistically between the groups. Extra-alveolar time with unphysiologic storage was longer than 15 min in 81 teeth. The results were statistically different for pulpal healing (A >> B > C), loss of marginal bone (C > A), amount of replacement resorption (A and B > C), alveolar growth inhibition (A > B >> C), local gingivitis (B > A and C) and buccal gingival retraction (C > A and B). Only 3 of 23 extracted teeth were lost because of replacement resorption alone. Only 2 of the 23 extracted teeth showed revascularization of the pulp. The results suggested that replanting avulsed teeth should be considered a temporary solution in children and adolescents. In these patients, the benefit of tooth replantation is mainly the time gained to establish an optimal treatment plan. Mature teeth with a necrotic periodontal ligament replanted in children before the pubertal growth spurt seemed to have the poorest prognosis. PMID- 9972161 TI - Tube-like mineralization in the dental pulp of traumatized primary incisors. AB - Mineralization in the pulp is a common finding in permanent as well as primary teeth and is associated with caries, aging, traumatic injuries and systemic conditions. This article describes an unusual pattern of pulpal calcification. A tube-like calcified structure formed in the dental pulp of primary incisors following mild traumatic injuries. It was studied by clinical, radiographic and histologic evaluation and by scanning electron microscopy. The tube-like structure was found to extend along the entire length of the pulp canal. Generally it was separated from the root dentin by normal pulp tissue, but was connected to the dentin in some sites. It had the histologic appearance of osteodentin with cell inclusions in a ring-like formation that was incomplete in places. The scanning electron microscope study showed rough inner and outer surfaces of a tube-like structure with openings that seemed to be dentinal tubules. PMID- 9972162 TI - Mandibular central incisor with two root canals. AB - A case report of a mandibular central incisor with two root canals and two separate apical foramina is presented. The tooth showed inadequate endodontic treatment and a periapical radiolucent lesion. The lesion healed following endodontic retreatment and proper obturation of both root canals. PMID- 9972163 TI - Treatment of maxillary molars with vertical fractures. AB - To date, there has been no reliable method for treating bucco-palatal fractured maxillary molar teeth. We have developed a simple repositioning method to fix teeth fractured in this way using wire. The effectiveness of this new approach was evaluated in both in vitro experimental research and clinical studies. PMID- 9972164 TI - Whither authorship? PMID- 9972165 TI - HIV topic update: protease inhibitor therapy and oral health care. AB - Protease inhibitors have been a major advance in the management of HIV disease and have reduced the frequency and severity of many complications, including some oral lesions. They may also be of value in the management of occupational exposures to the virus. However, they may produce adverse effects including oral symptoms such as paraesthesia, taste disturbances and xerostomia, and may interact with a number of drugs used in oral health care. This article summarises the current situation. PMID- 9972166 TI - Oral manifestations of HIV in a southeast USA population. AB - OBJECTIVES: Examine variations in oral manifestations of HIV by gender, race, risk behaviors, substance use and immune status in a previously unstudied population in the southeast region of the USA. DESIGN: Cross-sectional analytic study. SETTING: Academic medical center, North Carolina, USA. SUBJECTS: First 238 HIV-infected adults (76% male; 59% Black) enrolled in an ongoing longitudinal study. METHODS: Oral examination, medical chart review, sociodemographic and behavioral interview. Descriptive, bivariate, and multivariable analyses. OUTCOMES: Presence of oral manifestations of HIV. RESULTS: 50% had recent CD4 counts < 200 cells microliters-1, 48% had one or more oral lesion. Specific lesion prevalence: hairy leukoplakia (OHL) 26.5%; candidiasis (OC) 20%; HIV associated periodontal diseases (HIV-PD) 8.8%; aphthae 4.2%; papillomas 2.5%; herpes simplex 2.1%; HIV salivary gland disease 2.1%; Kaposi's sarcoma (KS) 1.7%; other 1.3%. In bivariate analyses, OHL was associated with being male, White, having a CD4 < 200, and men who have sex with men (MSM); OC was associated with CD4 < 200 and current smoking; HIV-PD was associated with consumption of more than seven alcohol-containing drinks per week; KS was associated with being male and MSM. Significant variables in multivariable analysis for presence of any oral lesion were White, CD4 < 200, and more than seven drinks/week; for OHL were male and CD4 < 200; and for OC were White, CD4 < 200, current smoking, and not MSM. CONCLUSIONS: MSM were at increased risk for KS and OHL, not OC, while smokers were at increased risk of OC. OC, OHL, and any oral lesion were associated with immune suppression. OHL was more likely in males independent of CD4 count. PMID- 9972168 TI - Fine needle aspiration cytology as a diagnostic test for oral squamous cell carcinoma. AB - OBJECTIVE: The purpose of this study was to determine the possibility of using fine needle aspiration cytology (FNAC) as a primary diagnostic test in oral leukoplakia and squamous cell carcinoma. MATERIALS AND METHODS: The sample consisted of 12 cases of oral leukoplakia and 60 cases of oral squamous cell carcinoma. FNAC and biopsy was done on all cases. A cytological and histopathological correlation was undertaken to determine the proportion of cancers that can be accurately diagnosed by FNAC and its ability to identify differentiation gradings of squamous cell carcinomas. A blind examination was undertaken. RESULTS: In oral leukoplakias equal rates of true positive and false negative results were obtained. The overall positive correlation accounted for 33.33% with 33.33% inadequate FNACs. In oral squamous cell carcinomas 92.85% of true positive and 7.14% of false negative results were obtained. The differentiation gradings correlated in only 41.07%. The overall positive correlation was 86.66% with 6.66% inadequate FNACs. CONCLUSIONS: The present study indicates that FNAC can be used as a reliable diagnostic test for oral squamous cell carcinoma but its use in oral leukoplakia is of limited value. PMID- 9972167 TI - The porphyromonas gingivalis prtP/kgp homologue exists as two open reading frames in strain 381. AB - P. gingivalis is considered to be a major pathogen of adult periodontitis. Among its cadre of putative virulence factors are hemagglutinins (adhesins) and proteases. We here report the cloning, sequencing and characterization of two genes, designated kgp(381) and hagD. Kgp(381), an open reading frame (ORF) of 1095 bp encoding a 40.1 kda protein, has high homology to the proteolytic domain of cysteine protease/hemagglutinin genes. HagD, an ORF of 4077 bp encoding a 147.1 kda protein, contains one HArep sequence which establishes it as an additional member of the HArep multigene family. Although similar in sequence to kgp and prtP which were identified from strains HG66 and W12, respectively, the kgp(381)-hagD genes have several characteristics which distinguish them from kgp and prtP. Foremost among these is a single base difference which produces a termination codon and an immediate frame shift resulting in two ORFs in strain 381 as compared to one ORF in strains HG66 and W12. In addition, a 172 amino acid sequence near the C-terminal end of hagD has very low identity (20.5-27.8%) to the corresponding region of kgp and prtP. These demonstrate that the homologue of kgp and prtP in strain 381 occurs as two separate genes which may genetically separate the adhesive and enzymatic domains of Kgp and PrtP proteins. Reverse polymerase chain reaction (PCR) analysis indicates that hagD expression is regulated by hemin concentration. PMID- 9972169 TI - Immunohistochemistry of 'tertiary lymphoid follicles' in oral amalgam-associated lichenoid lesions. AB - OBJECTIVES: To characterise lymphoid follicle-like aggregates incidentally found to occur in biopsies of oral lichenoid reactions (OLR) and to correlate the findings to hyperplastic tonsil follicles. DESIGN: An immunocytochemical analysis of archival material. SUBJECTS AND METHODS: In an arbitrarily selected period 1992-1994 with a total of 13,924 oral biopsies, 2407 cases were signed out as OLR or lichen planus. These were microscopically reviewed, with the purpose to retrieve all cases showing histologic changes resembling secondary lymphoid follicles. RESULTS: 87 cases showed lymphoid follicle-like changes and 82 of these were in oral regions known to constitutively lack 'organised MALT'. Unexpectedly, all of the 82 were found retrospectively to be in close or direct contact with amalgam fillings. Immunocytochemically, using antibodies to B and T cells, macrophages, follicular dendritic cells and proliferation and apoptosis markers, the mucosal follicles stained similar to tonsillar secondary follicles. In several of an additional 11 OLR cases with histologic changes suggestive of primary follicles, we also found immunocytochemical evidence of such changes. CONCLUSIONS: 'Tertiary lymphoid follicles' may occasionally develop in OLR at sites of the oral mucosa constitutively lacking organised lymphoid tissue. The microenvironment of the OLR T cell infiltrate may occasionally favour such follicle development and amalgam constituents may causally be involved in an unknown way. PMID- 9972170 TI - An immunohistochemical study of p53 and PCNA in inflammatory papillary hyperplasia of the palate: a dilemma of interpretation. AB - OBJECTIVE: Inflammatory papillary hyperplasia of the palate (IPHP) or the granular type of denture stomatitis, is a non-neoplastic lesion characterized histologically by a significant epithelial hyperplasia and inflammatory infiltrate usually caused by trauma and Candida infection. p53 and proliferative cell nuclear antigen (PCNA) are cell-cycle regulators, that when overexpressed, are considered by many investigators as markers of malignant transformation. The objective of this study was to investigate the immunodetection of p53 and PCNA in IPHP, and to correlate these results with the degree of epithelial hyperplasia and inflammatory infiltrate. MATERIALS AND METHODS: In 12 cases diagnosed clinically as IPHP, Candida was cultured from the denture base and the palatal mucosa. Lesions were biopsied and stained with H&E for histomorphometric analysis of the epithelial width and inflammatory infiltrate. PAS and Gram stains were used for screening of Candida. Sections were immunostained with DO-7 for p53 and PC-10 for PCNA. Fifteen palatal biopsies obtained from autopsies of edentulous subjects with normal palatal mucosa served as controls. RESULTS: All cultures of swabs from both the palatal mucosa and denture base were positive for Candida. Candidal hyphae could not be identified in PAS stained sections. Small foci of Gram-positive organisms were found in two cases of IPHP. Epithelial width and inflammation were significantly higher in IPHP than in controls (P < 0.001). A three-fold increase in positively stained cells for p53 and a two-fold increase in positively stained cells for PCNA were seen in IPHP compared with controls (P < 0.001). CONCLUSIONS: Although a significant increase in the immunodetection of p53 and PCNA may indicate a malignant potential, IPHP has never been reported to undergo malignant transformation nor is it associated with cytologic signs of dysplasia. The increase in the epithelial width and inflammation degree is probably associated with the colonization of the denture bases with Candida organisms. The increased detection of p53 and PCNA can be a secondary effect of cytokines originating from both the inflammatory cells and the keratinocytes. Thus, immunodetection of p53 and PCNA by current immunohistochemical methods on archival tissues is neither specific nor sensitive enough to be used as indicators for malignant potential in the absence of cytological dysplastic changes or genetic proof of mutated cell cycle genes. PMID- 9972171 TI - Dietary factors in oral leukoplakia and submucous fibrosis in a population-based case control study in Gujarat, India. AB - OBJECTIVES: To investigate the relationship of specific nutrients and food items with oral precancerous lesions among tobacco users. DESIGN: A population-based case-control study. SETTING: Villages in Palitana taluk of Bhavnagar district, Gujarat, India. SUBJECTS AND METHODS: An interviewer-administered food frequency questionnaire, developed and validated for this population, was used to estimate nutrient intake in blinded, house-to-house interviews. Among 5018 male tobacco users, 318 were diagnosed as cases. An equal number of controls matched on age (+/- 5 years), sex, village, and use of tobacco were selected. MAIN OUTCOME MEASURES: Odds ratios (OR) from multiple logistic regression analysis controlling for relevant variables (type of tobacco use and economic status). RESULTS: A protective effect of fibre was observed for both oral submucous fibrosis (OSF) and leukoplakia, with 10% reduction in risk per g day-1 (P < 0.05). Ascorbic acid appeared to be protective against leukoplakia with the halving of risk in the two highest quartiles of intake (versus the lowest quartile: OR = 0.46 and 0.44, respectively; P < 0.10). A protective effect of tomato consumption was observed in leukoplakia and a suggestion of a protective effect of wheat in OSF. CONCLUSION: In addition to tobacco use, intake of specific nutrients may have a role in the development of oral precancerous lesions. PMID- 9972172 TI - Snuff use and smoking among senior high school students: effects of a snuff sales ban. AB - OBJECTIVES: The popularity of snuff especially among adolescents is rising. The association between long-term snuff use and oral cancer discovered in epidemiological studies has prompted a variety of preventive measures to be taken to reduce snuff use and prevent adoption of the habit. In this study, the effect of a recent (1 March, 1995) snuff sales ban introduced in Finland was investigated. Further, the rates of smoking, snuff use, alcohol use and drug experimenting were investigated before the introduction of the ban to characterize the study population. DESIGN AND SUBJECTS: Two questionnaire studies were carried out. The first was carried out 3 months prior to the ban in 1994 and the second 9 months after the ban in 1995 in a senior high school population in southwestern Finland. The participants were 793 students (aged 15-22 years) in the first survey and 545 students (aged 16-23) in the second. Associations between variables were analyzed using cross-tabulation and step-wise logistic regression. The effects of the ban were determined on the basis of direct questions in the second questionnaire relating to the snuff sales ban. RESULTS: Snuff was used by 9% of the students participating in the first study. The results of the second questionnaire indicate that the implementation of the snuff sales ban reduced the rate of snuff use by 1% in the study population. The majority of the snuff users (76%) reported that they had maintained their snuff habit. Of those reporting that they were snuff users before implementation of the snuff sales ban, 12% had switched to smoking and 5% to drugs. CONCLUSIONS: The results of the present study suggest that the snuff sales ban in this population with a high rate of snuff use had little effect on snuff use rates and may have some short-term negative consequences as some snuff users switch to other substitutes, such as smoking, with known adverse health effects. PMID- 9972175 TI - Society of Critical Care Medicine 28th Educational and Scientific Symposium. San Francisco, California, USA. January 23-27, 1999. Abstracts. PMID- 9972173 TI - Anti-calculus activity of a toothpaste with microgranules. AB - OBJECTIVE: The objective of the trial was to determine the efficacy of the proven anticalculus active system (zinc citrate trihydrate [ZCT] and triclosan), when the ZCT is delivered from microgranules incorporated in a silica-based toothpaste containing 1450 ppm F as sodium fluoride. DESIGN: A monadic, single-blind, two phase design clinical trial was used to compare the effect of the test and a negative control fluoridated toothpaste on the formation of supragingival calculus. SUBJECTS AND METHODS: Male and female calculus-forming volunteers, aged 18 or over, were recruited for the study following a 2-week screening phase. All subjects were given a scale and polish of their eight lower anterior teeth at the start of both the pre-test and test phases. Subjects were supplied with a silica based 1450 F ppm fluoridated toothpaste with no anti-calculus active for use during an 8-week pre-test phase. Calculus was assessed at the end of the pre-test and test phases using the Volpe-Manhold index (VMI). Subjects were stratified according to their pre-test VMI score (8-10, 10.5-12, > 12) and gender and then allocated at random to test or negative control toothpaste groups. Subjects with < 8 mm of calculus were excluded from further participation. MAIN OUTCOME MEASURE: The outcome variable was the mean VMI score for the test and negative control groups. RESULTS: The test toothpaste caused a statistically significant 30% reduction in calculus compared with the control paste after a 13-week use. No adverse events were reported during the study. CONCLUSION: The incorporation of the ZCT in microgranules did not adversely affect the anticalculus activity of the new formulation. PMID- 9972174 TI - An overview of the complexities and subtleties of immunohistochemistry. AB - Immunohistochemistry has the potential to be a powerful research tool. However, immunohistochemical studies are frequently undertaken without regard to the complexities and subtleties of these useful techniques. This review aims to address the problems and limitations that are often encountered, and the procedures that should be considered in both the planning and interpretation of immunohistochemical studies. Particular reference is made to the generation of functionally different protein isoforms from a single gene by alternative splicing and post-translational modifications, primary antibody selection, the effects of tissue manipulation such as fixation and antigen retrieval, the need for appropriate controls and interpretation of staining patterns. PMID- 9972176 TI - American Academy of Allergy, Asthma and Immunology, (AAAAI) 55th annual meeting. Orlando, Florida, USA. February 26-March 3, 1999. Abstracts. PMID- 9972177 TI - 76th Annual session of the American Association of Dental Schools. Vancouver, British Columbia, Canada, March 8-9, 1999. Abstracts. PMID- 9972179 TI - Cumulative index, 1994 through 1998. PMID- 9972178 TI - American College of Cardiology 48th annual scientific session. New Orleans, Louisiana, USA. March 7-10, 1999. Abstracts. PMID- 9972180 TI - School-based intervention using a dual-theory model. PMID- 9972181 TI - ADA plans for flurry of state legislative action in 1999-2000. PMID- 9972182 TI - The healthy heart--challenges and opportunities for dietetics professionals in the 21st century. PMID- 9972183 TI - Estimated intakes of trans fatty and other fatty acids in the US population. AB - OBJECTIVE: To estimate mean level of trans fatty acid intakes using a representative sample of the US population. DESIGN: The study used food intake data from the 1989-1991 Continuing Survey of Food Intakes by Individuals (CSFII) and the trans fatty acid contents of specific foods calculated from a database compiled by the US Department of Agriculture (USDA) to estimate the mean level and deciles of trans fatty acid intake of the representative US population. SUBJECTS/SETTING: Trans fatty acid intakes were estimated for each subject (N = 11,258) in the CSFII data who completed both a 24-hour recall and a 2-day food record. STATISTICAL ANALYSES PERFORMED: Weights developed by USDA for the survey were used for all data analyses. The Technical Assessment Systems (TAS) International Diet Research System (TAS-DIET), software developed by TAS, was used to derive weighted estimates of the mean and percentiles of the intake distribution. PC CARP, software designed by Iowa State University, was used to estimate standard errors. RESULTS: Mean percentage of energy ingested as trans fatty acids was 2.6% and the mean percentage of total fat ingested as trans fatty acids was 7.4%. Across all age and gender groups examined, estimates ranged from 2.6% to 2.8% and 7.1% to 7.9%, respectively. APPLICATIONS/CONCLUSIONS: Dietetics practitioners can use the representative data of this study to help clients achieve desired changes in consumption levels of trans fatty acids. PMID- 9972184 TI - Impact of adopting lower-fat food choices on energy and nutrient intakes of American adults. AB - OBJECTIVE: To evaluate the energy and nutrient intake of free-living men and women who choose foods consistent with different fat-reduction strategies. DESIGN: For each year of the Continuing Survey of Food Intake by Individuals from 1989 through 1991, food codes were used to sort respondents by type of milk; type of meats; and type of cheese, yogurt, salad dressing, cake, and pudding (i.e., full-fat or fat-modified products) consumed. SUBJECTS: A nationally representative sample of 3,313 men and 3,763 women who completed 3-day intake records and consumed either a reduced-fat or full-fat food from at least 1 of the 3 fat-reduction strategy categories. STATISTICAL ANALYSIS PERFORMED: Analysis of variance with the Scheffe test was used to analyze differences in energy and nutrient intake between exclusive users, mixed users, and nonusers of each strategy or combined strategies. RESULTS: Regardless of fat-reduction strategy, men and women who used them reported significantly lower intakes of total fat (up to 18 g lower), saturated fat (up to 12 g lower), cholesterol (up to 75 mg lower) and energy compared with nonusers. Exclusive users of single strategies met or approached recommendations of the National Cholesterol Education Program for total fat, saturated fat, and cholesterol intake; micronutrient intake varied depending on the strategy used. Skim milk users had the most favorable micronutrient intake, whereas lean meat users reported inadequate intake of zinc (men 63% and women 59% of the Recommended Dietary Allowances [RDAs]) and female users of fat-modified products reported inadequate intakes of vitamin E (64% of RDA) and zinc (65% of RDA). Multiple-strategy users achieved National Cholesterol Education Program goals and reported adequate micronutrient intakes and significantly lower energy intake. Mixed users of fat-modified products compared with nonusers of any fat-modified products had adequate micronutrient intake and lower intakes of total fat (32% vs 36% of energy for men and 32% vs 35% of energy for women) and saturated fat (11% vs 13% of energy for men and 11% vs 12% of energy for women). In addition, nonusers of any fat-modified strategy had the highest cholesterol and energy intake and the lowest intake of many micronutrients. APPLICATIONS: A variety of fat-reduction strategies can be implemented to reduce energy, total fat, saturated fat, and cholesterol intake. Some of the strategies were associated with an inadequate micronutrient intake, so additional dietary guidance is needed to ensure that all nutrient requirements are met. Furthermore, people who do not use any fat-reduction strategy or those who exclusively use lean meats or fat-modified products would benefit from understanding how to balance their food choices. PMID- 9972185 TI - Dietary intake of modernizing Samoans: implications for risk of cardiovascular disease. AB - OBJECTIVE: To describe the dietary intake of American and Western Samoans, with emphasis on nutrients conventionally related to risk factors for cardiovascular disease. DESIGN: Cross-sectional dietary survey. Intake estimates were based on 24-hour recall interviews. SUBJECT: Community-based samples of 946 men and women (455 American Samoans, 491 Western Samoans) aged 25 to 55 years. STATISTICAL ANALYSES: Tests of differences in means (t tests) and proportions (chi 2 tests). Correlation and multivariate linear regression analyses were conducted to describe correlates of energy and nutrient intakes. RESULTS: Few differences were noted between the energy and nutrient intakes of men and women, but substantial differences were found between residents of American Samoa and those of the less modernized country of Western Samoa. American Samoans consumed significantly more energy as carbohydrate (47% vs 44%) and protein (18% vs 13%) and less as fat (36% vs 46%) and saturated fat (16% vs 30%). Energy-adjusted intakes of cholesterol and sodium were higher among American Samoans. These differences persisted after adjustment for age, gender, years of education, occupation, and categories of a 10-point material lifestyle score. Samoans in the lowest category of material lifestyle had significantly lower energy-adjusted intakes of protein, cholesterol, and sodium and higher intakes of saturated fat than those in the upper 2 categories. Additional analyses described the contribution of specific foods to the intakes of energy and macronutrients. CONCLUSIONS/APPLICATIONS: The observed energy and nutrient intake patterns are consistent with previously reported levels of obesity and risk factors for cardiovascular disease among Samoans and suggest dietary modification for those at highest risk. Dietetics practitioners who counsel Samoan and other Pacific Islander clients should be aware of these intake patterns, which seem particularly malleable to levels of personal income. More generally, results from this study illustrate that the food choices of certain ethnic groups may be profoundly affected by the process of modernization within a country or by migration to a more economically developed locale. PMID- 9972186 TI - Nutritional effects of long-term gastrostomy feedings in children with cystic fibrosis. AB - OBJECTIVE: To analyze the long-term nutritional effects of supplemental gastrostomy feedings in undernourished patients with cystic fibrosis. DESIGN: Longitudinal, retrospective assessment of anthropometric measures before and for up to 4 years after gastrostomy. SUBJECTS/SETTING: All patients at a large cystic fibrosis care center who underwent gastrostomy between 1980 and 1993 when they were at least 1 year old and were followed up for a minimum of 1 year after gastrostomy. STATISTICAL ANALYSES PERFORMED: The Mann-Whitney U test was used to compare anthropometric values measured during 4 postgastrostomy time intervals with values measured during the year preceding gastrostomy. RESULTS: The 21 patients ranged in age from 1.1 to 20.8 years (median age = 7.4 years). They had mild to moderate malnutrition at the time of gastrostomy. Patients were followed up for a mean of 39 months after gastrostomy. Supplemental feedings were associated with significant improvements in weight and height percentiles for age, and in weight as a percentage of ideal weight. Improvement in weight occurred earlier than improvement in height. Among subjects followed up for at least 18 months after gastrostomy, median weight percentile for age increased from 2% for the year before gastrostomy to 12% for the period 6 to 18 months after gastrostomy (P < .001) and 19% for the period 30 to 48 months after gastrostomy (P = .002 compared with before gastrostomy). Other nutritional parameters followed similar, although less dramatic patterns. Gastrostomy feedings were well tolerated and associated with only minor complications. CONCLUSIONS: Long-term gastrostomy feedings appear to be a safe and effective means of improving nutrition in malnourished patients with cystic fibrosis. Clinical dietitians should function as care managers for patients with cystic fibrosis who are receiving supplemental gastrostomy feedings. PMID- 9972187 TI - Elevated resting energy expenditure in adolescents with sickle cell anemia. AB - OBJECTIVE: To assess the reliability of standard prediction equations in estimating resting energy expenditure (REE) values in adolescents with sickle cell anemia. SUBJECTS/DESIGN: Body composition and metabolic measurements were performed in 8 adolescents, aged 11 to 18 years, with homozygous sickle cell anemia. REE was measured by indirect calorimetry under standard conditions, and measurements were compared with 4 prediction formulas (Harris-Benedict, Schofield, Mayo Clinic, and Food and Agriculture Organization/World Health Organization/United Nations University). Fat-free mass was measured to assess REE per unit of actively metabolizing tissue. Fat-free mass was expressed as a mean of values obtained by densitometry, deuterium dilution, 40K-counting, and total body electrical conductivity. STATISTICAL ANALYSES: Repeated measures analysis of variance was performed to determine whether measured REE values and predicted values differed. The Fischer test was used to identify which predicted values differed significantly from the measured REE. RESULTS: All 4 prediction formulas significantly underestimated REE. Group mean values for the prediction formulas ranged from 83% to 89% of the measured value. REE averaged 47.7 +/- 10.0 kcal/kg fat-free mass per day, which is 30% to 50% higher than reported values in healthy adolescent populations. CONCLUSIONS: These data suggest that REE is elevated in adolescents with sickle cell anemia. Standard equations used to predict REE are unreliable in these patients. APPLICATIONS: REE in patients with sickle cell anemia is best determined by indirect or direct measurement of energy expenditure. Clinically useful formulas to estimate REE should be developed for patients with conditions, including sickle cell anemia, where the metabolic rate may be altered. PMID- 9972188 TI - Water: an essential but overlooked nutrient. AB - Water is an essential nutrient required for life. To be well hydrated, the average sedentary adult man must consume at least 2,900 mL (12 c) fluid per day, and the average sedentary adult woman at least 2,200 mL (9 c) fluid per day, in the form of noncaffeinated, nonalcoholic beverages, soups, and foods. Solid foods contribute approximately 1,000 mL (4 c) water, with an additional 250 mL (1 c) coming from the water of oxidation. The Nationwide Food Consumption Surveys indicate that a portion of the population may be chronically mildly dehydrated. Several factors may increase the likelihood of chronic, mild dehydration, including a poor thirst mechanism, dissatisfaction with the taste of water, common consumption of the natural diuretics caffeine and alcohol, participation in exercise, and environmental conditions. Dehydration of as little as 2% loss of body weight results in impaired physiological and performance responses. New research indicates that fluid consumption in general and water consumption in particular can have an effect on the risk of urinary stone disease; cancers of the breast, colon, and urinary tract; childhood and adolescent obesity; mitral valve prolapse; salivary gland function; and overall health in the elderly. Dietitians should be encouraged to promote and monitor fluid and water intake among all of their clients and patients through education and to help them design a fluid intake plan. The influence of chronic mild dehydration on health and disease merits further research. PMID- 9972189 TI - Hyperhydrating with glycerol: implications for athletic performance. AB - Small decreases in hydration status can result in a dramatic decrement in athletic performance and greatly increase the risk of thermal injury. Because of its osmotic properties, which enable greater fluid retention than the ingestion of water alone, glycerol has been proposed as a hyperhydrating agent. In fact, glycerol is now commercially available and marketed as a sport supplement to be ingested with water or sport drinks; thus, dietitians need to be cognizant of this new addition to the sports nutrition table. The results of glycerol-induced hyperhydration research have been equivocal, most likely because of methodologic differences between studies, such as variations in the intensity of exercise, environmental conditions, and concentration or dose of glycerol administered. Although the suggested dosage of glycerol depends on body size and varies between manufacturers, 1 g/kg body weight with an additional 1.5 L fluid taken 60 to 120 minutes before competition is standard. Some test subjects reported feeling bloated or nauseated after ingesting glycerol. This review examines glycerol induced hyperhydration research and the safety of ingesting glycerol, discusses commercial availability of glycerol, and makes recommendations for glycerol induced hyperhydration research. PMID- 9972190 TI - Physical activity--it's not reserved for athletes. PMID- 9972191 TI - Characteristics and occurrence of phenolic phytochemicals. AB - Phenolic phytochemicals are the largest category of phytochemicals and the most widely distributed in the plant kingdom. The 3 most important groups of dietary phenolics are flavonoids, phenolic acids, and polyphenols. Flavonoids are the largest group of plant phenols and the most studied. Phenolic acids form a diverse group that includes the widely distributed hydroxybenzoic and hydroxycinnamic acids. Phenolic polymers, commonly known as tannins, are compounds of high molecular weight that are divided into 2 classes: hydrolyzable and condensed tannins. Quantification of food phenolics is just beginning, and preliminary results indicate high variability, even within a given food. Phenolics are biologically active compounds that may possess some disease preventive properties. Evidence for their ability to prevent cancer or heart disease is preliminary and conflicting. The health benefits of phytochemicals have been reported in the popular press, and the public will come to dietitians for answers to their questions about phytochemicals. PMID- 9972192 TI - Nutrient intake of children eating school breakfast. PMID- 9972193 TI - Nutritional patterns and needs of migrant farm workers in northwest Michigan. PMID- 9972194 TI - Consumers prefer unseasoned lean ground beef patties to patties made from turkey breast or emu. PMID- 9972195 TI - Position of the American Dietetic Association: medical nutrition therapy and pharmacotherapy. AB - It is the position of The American Dietetic Association that medical nutrition therapy and lifestyle counseling are integral components of medical treatment for the management of selected conditions for which pharmacotherapy is indicated. The Association promotes a team approach to care for clients receiving pharmacotherapy and encourages active collaboration among dietetics professionals and other members of the health care team. Numerous chronic medical conditions respond to medical nutrition therapy; however, pharmacotherapy may be needed to achieve control. In some cases, medical nutrition therapy and pharmacotherapy may need to be initiated simultaneously. Medical nutrition therapy is critical to the management of a variety of chronic diseases, is effective in managing disease, and is cost-effective. The use of a coordinated multidisciplinary team effort is critical to the success of medical nutrition therapy and pharmacotherapy. Because medical nutrition therapy with pharmacotherapy is a treatment of long duration that requires monitoring of compliance and effectiveness, it is best accomplished through a team approach. PMID- 9972196 TI - ADA positions: science-based consumer messages. Association Positions Committee. PMID- 9972197 TI - President's page: personal responsibility and food safety. PMID- 9972198 TI - Vaccination for the new millennium. PMID- 9972199 TI - Inadequate control of lipid levels in patients with a previous myocardial infarction. AB - AIM: To access the current lipid management of late survivors of acute myocardial infarction. METHODS: A systematic follow-up of all survivors who had previously been screened for enrolment into one of three randomised clinical trials in Auckland was undertaken from December 1995 to January 1997. All contacted survivors were asked to answer a questionnaire regarding their current therapy and were invited to undergo venepuncture for a lipid assay. RESULTS: Of the 1036 patients with acute myocardial infarction screened for enrolment in the three trials there were 984 (95%) who survived 30 days. At a median of 5.5 years (interquartile range 3.2-8.5) follow-up, 641 (86%) survivors agreed to have a fasting lipid test. The mean total cholesterol level was 5.7 +/- 1.1 mmol/L high density lipoprotein cholesterol 1.1 +/- 0.3 mmol/L, low density lipoprotein cholesterol 3.8 +/- 0.9 mmol/L and triglyceride level 1.9 +/- 1.1 mmol/L. Two hundred and seven (32%) patients were treated with a lipid-modifying agent. Four hundred and forty-five (69%) patients had a cholesterol level > or = 5.2 mmol/L 381 (59%) patients had a level > or = 5.5 mmol/L and 72 (11%) patients had a level > or = 7.0 mmol/L of whom 62 patients were not being treated with a lipid modifying agent. For the 107 patients with coronary artery bypass grafts, the mean cholesterol level was 5.4 mmol/L and the mean low density lipoprotein cholesterol level was 3.7 +/- 0.9 mmol/L, with 57 (53%) patients not being treated with a "statin" or "fibrate". CONCLUSION: Lipid management is suboptimal in this high risk population of patients post-infarction and greater efforts need to be made to achieve better control. Diet is frequently inadequate in these patients at high risk and statin therapy is indicated. PMID- 9972200 TI - A measles epidemic controlled by immunisation. AB - AIM: In 1997, an immunisation campaign, using measles-mumps-rubella vaccine, was planned for children aged 2-10 years to prevent a measles epidemic predicted by mathematical modelling. The epidemic started before the campaign and is described here. METHOD: Measles hospitalisation, notification and laboratory data were combined. RESULTS: The epidemic started in April 1997 and was largely over by January 1998. No deaths were identified and only one hospitalisation was coded as measles encephalitis, compared to seven deaths and ten cases of measles encephalitis in the 1991 epidemic. For the 12 months from 1 March 1997 there were 2,169 (60 per 100,000) measles cases identified, 314 (9 per 100,000) of whom were hospitalised. Two-thirds of hospitalised cases were notified. The age standardised measles incidence rates were 33, 34, and 174 per 100,000 for Europeans, Maori and Pacific people, respectively. The respective age standardised hospitalisation rates were 4, 9 and 32 per 100,000. Measles incidence was highest for under one-year-olds (904 per 100,000) and low for 11-16 year-olds (27 per 100,000)--the cohort previously offered a second vaccine dose. Most cases were aged 10 years and under, and this group were the main drivers of virus transmission. CONCLUSIONS: The immunisation campaign prevented 90-95% of predicted cases. The campaign was appropriately targeted at children aged 10 years and under. PMID- 9972201 TI - The incidence of hepatocellular carcinoma in New Zealand. AB - AIM: To measure the incidence rate of hepatocellular carcinoma (HCC) in New Zealand, by ethnicity, sex, region and age. METHODS: Cancer Registry data for 1983-94 were used to calculate rates of primary liver cancer (ICD code 155.0) and HCC (both ICD code 155.0 and ICD-O morphology code 8170) directly standardised to Segi's world population and standardised for region. RESULTS: Rates of HCC per 100,000 person years 6.6 and 1.3 for Maori males and females, 14.7 and 4.6 for Pacific people, and 0.8 and 0.3 for Other (inclusive of Chinese). The rates for Chinese for 1989-94 were 19.9 and 5.8. These rates are likely to be underestimates due to imperfect sensitivity of ICD-O code 8170 registrations for HCC. The rates of HCC for Maori and Pacific people (sexes combined) were 7.3 and 18.0 times that for other for 1983-94; the HCC rate for Chinese was 25.8 times greater than Europeans for 1989-94. Rates of HCC tended to be higher in the north of New Zealand, compared to the south, for Maori and Other/Europeans, but there was no apparent regional gradient for Pacific people and Chinese. CONCLUSIONS: Non-Europeans have higher rates of HCC than Europeans due to variations in hepatitis B carriage. Males have higher rates than females, and Maori and Europeans living in the north of New Zealand have higher rates of HCC than those living in the south. It is estimated that any hepatitis B screening and follow-up programme will detect one incident case of HCC per year per 2000 hepatitis B carriers in the target population, or one incident case per 1000 carriers actually participating in regular follow-up. PMID- 9972202 TI - Audit of early experience with inhaled nitric oxide in New Zealand neonatal intensive care units. AB - AIMS: To audit the use of inhaled nitric oxide for the treatment of persistent pulmonary hypertension of the newborn in New Zealand neonatal intensive care units. METHODS: Prospective data collection on all infants treated with inhaled nitric oxide in neonatal intensive care units in the 20-month period from first use to December 1995. Data included perinatal factors, principal diagnosis, echocardiogram results, ventilation details and response to nitric oxide, adverse reactions and outcome. RESULTS: Twenty-eight infants received nitric oxide in three centres, all bar one being 36 weeks or more gestation. Overall survival was 68%. Thirteen infants (46%) responded to nitric oxide treatment, 12 (92%) surviving. Seven (47%) of non-responders survived. Infants with primary pulmonary hypertension or meconium aspiration syndrome had 90% survival and more often responded to nitric oxide than infants with congenital diaphragmatic hernia (40% survival) or pulmonary hypoplasia (no survivors). No serious complications of treatment were recorded. CONCLUSIONS: Inhalational nitric oxide was not universally successful treatment for pulmonary hypertension of the newborn but was likely to have been life-saving in a proportion of cases. Future studies may allow better case selection. Ongoing audit of this new treatment is warranted. PMID- 9972203 TI - Doctors, capitation payments and the first Labour Government. AB - The Health Funding Authority (HFA) proposes to change the way general practitioners (GPs) are paid for patient visits. Most doctors charge patients a fee for each visit, minus a subsidy from the general medical services benefit where applicable for those holding community services cards. Seeking to set strict limits on costs, the HFA proposes a block or 'capitation' payment for all practices based on the number and age of patients. Almost 60 years ago the first Labour government proposed just such a payment for the general practitioner service outlined in the Social Security Act 1938. Led by the local branch of the British Medical Association, doctors eventually persuaded the government to offer instead a statutory fee-for-service. They could charge their patients over and above this fee. This article shows how and why the Labour Government compromised in this way so that doctors' payment did not come wholly from the state, and that they remained independent professionals. PMID- 9972205 TI - [The mammography report]. PMID- 9972204 TI - SIDS and the toxic gas theory. PMID- 9972206 TI - [Magnetic resonance in congenital cardiopathy. Part I]. PMID- 9972207 TI - [Role of magnetic resonance in hemodialysis patients with amyloid shoulder arthropathy]. AB - PURPOSE: Amyloid shoulder arthropathy is a frequent finding in long-term hemodialysis patients. Assessing the symptoms is fundamental in the approach to these patients but their long life expectancy means that the correct imaging quantification of scapulohumeral joint impairment is just as important. We investigated the role of MRI in amyloid shoulder arthropathy in long-term hemodialysis patients. MATERIAL AND METHODS: From January, 1995, to December, 1996, twelve long-term (mean: 13 years) hemodialysis patients with amyloid shoulder arthropathy were examined with MRI. All of them had undergone physical examination to detect the most involved scapulohumeral joint. MRI was carried out with a 1.0 T Magnetom Impact unit (Siemens, Germany) using T1-weighted Turbo SE sequences at high resolution on coronal and sagittal planes, respectively parallel and perpendicular to the supraspinatus tendon, and FLASH sequences on the axial plane. Six patients were then submitted to surgery. RESULTS: MRI had identified 3/12 rotator cuff tears (always involving the supraspinatus tendon and other tendons), 7/12 rotator cuff tears from supraspinatus tendon injury, and 1/12 thickening and structural dishomogeneity of the supraspinatus tendon. Finally, no structural changes were shown in 1/12 cases. In addition, most MR examinations (11/12) showed some inhomogeneous material characterized by intermediate-to-low signal intensity on T1-weighted sequences; such changes were found in subacromial and subdeltoid bursas in part of the articular capsule and were always associated with hypointense nodular images in all sequences. Surgery was carried out in 6 patients and confirmed both the structural changes of the rotator cuff and the presence of amorphous material which appeared to be amyloid deposits at subsequent histology. MRI proved to be a very reliable tool even in the study of skeletal structural changes, permitting both the identification of periarticular calcifications and the accurate analysis and quantification of subchondral erosions. CONCLUSIONS: MRI was a very reliable tool not only in the study of rotator cuff tears due to amyloid deposition but also in the analysis of bone changes. Thus MRI could play a growing role in treatment planning. PMID- 9972208 TI - [Computerized tomography false positives in knee medial meniscus injuries. Retrospective study of 400 cases]. AB - PURPOSE: We retrospectively evaluated the diagnostic reliability of high resolution CT (HRCT) in the study of knee joint conditions. MATERIAL AND METHODS: We reviewed the results of 400 HRCT examinations of the knee performed in 1993 and compared them with arthroscopic findings. The patients were affected with knee pain and the physical findings were insufficient for diagnosis but a sufficient indication for further instrumental tests. CT slices were 1 mm, with .5 mm feed; the images were reconstructed on the coronal and sagittal planes (2 mm thickness and 2 mm gap) with a CT Sytec 3000 unit (GE Systems, Milwaukee, WI, USA). RESULTS: The patients positive for meniscal fracture were submitted to arthroscopy and operated on if positive arthroscopically. We had 164 surgical cases even though the meniscus was damaged in 236 cases. CT was negative in 16 of 164 surgical cases. The meniscal injury was demonstrated with both CT and arthroscopy in 236 cases; there were 8 false positives and 32 questionable cases. In the latter, arthroscopy showed 24 cases of meniscal degeneration and 8 horizontal fractures. Diagnostic accuracy was 96%. CT showed the 8 false positives as radial injuries of the free margin, but in fact they were false images caused by a normal fold which increases in knee valgus. DISCUSSION AND CONCLUSIONS: HRCT is more reliable than conventional CT (diagnostic accuracy: 96% vs 85-90%) and MRI (90% reliable). The use of thin slices also permitted to show that a meniscal tissue interruption on the radial margin is not referrable to fracture, as indicated also in the recent literature, but to a normal fold. PMID- 9972209 TI - [Diagnostic imaging in AIDS-related pulmonary Kaposi's sarcoma]. AB - INTRODUCTION: Kaposi's sarcoma is an uncommon multifocal angiogenic lesion but the most frequent tumor (15%) in HIV+ patients: it is found in homosexual HIV+ men in 95% of cases and appears as cutaneous-mucous lesions in most patients; the respiratory system is involved in 20% of cases. We investigated the yield of conventional radiography, CT and HRCT in the diagnostic imaging of pulmonary Kaposi's sarcoma. MATERIAL AND METHODS: We retrospectively reviewed the findings of 205 patients with cutaneous Kaposi's sarcoma. Chest radiography (two projections) had been performed in all of them, chest CT in 23, HRCT in 7, and tracheobronchial endoscopy in 20. RESULTS: The respiratory system was involved in 22% of the patients with cutaneous-mucous Kaposi's sarcoma. The pulmonary pattern was perivasculobronchial interstitial thickening with bilateral and symmetrical ilifugal involvement in 78% of cases, associated with multiple perivascular nodular opacities (< 1 cm) in 19 patients. Pleural effusion was seen in 52% of cases, while 3 patients had plaque thickening of visceral pleura; mediastinal adenopathy was found in 8.6% of cases. Endoscopy detected 14 tracheobronchial Kaposi's lesions. Kaposi's involvement of the respiratory system was confirmed histologically in 26 autopsy cases. CONCLUSIONS: In our experience, conventional radiology and clinical-history data permit to evaluate early pleuropulmonary involvement of Kaposi's sarcoma and to follow its evolution. CT and HRCT unquestionably detect the typical signs earlier than conventional radiology and yield further information on disease extent. PMID- 9972210 TI - [AIDS-related pulmonary Kaposi's sarcoma: role of high-resolution computerized tomography]. AB - INTRODUCTION: HIV-related Kaposi sarcoma (KS) is characterized by lesion multifocality, stronger progression and recurrent involvement of some internal organs. Pulmonary lesions are found in 18-47% of cases and not necessarily associated with skin involvement. Lung infections are potentially life threatening and their early and prompt demonstration is a crucial step for both treatment planning and the prognosis of this severe disease. As a rapid recognition of a pulmonary condition leads to a complete or partial regression in at least 50% of cases, we investigated the role and the diagnostic yield of HRCT in depicting HIV-related KS. MATERIAL AND METHODS: The findings of thirty-nine patients with HIV-related pulmonary KS were retrospectively reviewed. We excluded the patients with associated diseases and incomplete radiologic findings and included 12 patients who had a chest radiograph and a HRCT scanning at least. HRCT showed parenchymal and subpleural micronodules (< 10 mm) and macronodules (> 10 mm), with the halo sign in some cases; perivascular and peribronchial infiltrates, linear or irregular opacities, pleural effusions and enlarged lymph nodes were also seen. Chemotherapy response was also evaluated. RESULTS: All 12 patients had advanced AIDS. The chest films showed abnormal patterns, such as peribronchial and perivascular infiltrates which were most often in midlower pulmonary lobes (88.9%) and often symmetric. Nodules were depicted in 50% of cases and were often associated with peribronchial and perivascular infiltrates; they were always bilateral and characterized by the presence of macronodules in most cases. Eleven of 12 HRCT examinations were considered sufficiently accurate for evaluation, while a pleural effusion prevented lung assessment in one case. Peribronchial and perivascular infiltrates were the most frequent abnormal findings (83.3%), with bilateral involvement in 80% and mostly in the midlower lobes (90%). Parenchymal and subpleural nodules were depicted in 58.3% of cases and always had irregular borders; the halo sign was seen around the nodules in 2 cases and macronodules were found in 2 cases. Pleural effusions were seen in 3 cases and enlarged lymph nodes in 4. Lung KS diagnosis was always confirmed at pathology. The response to chemotherapy (ABV protocol) was evaluated in 5 patients: transient and definitive regressions were observed in 1 and 2 cases, respectively, and disease progression was seen in 2 cases. CONCLUSIONS: HRCT allows the accurate assessment of pulmonary KS in its different stages detailing the disease and its spread, which makes biopsy easier. It also permits to avoid more invasive diagnostic procedures and it is useful in the follow-up after chemotherapy. PMID- 9972211 TI - [Invasive aspergillosis in AIDS: findings with high-resolution computerized tomography]. AB - PURPOSE: To review the early CT findings of invasive aspergillosis in AIDS patients who are at high risk for developing this infection. Early recognition of invasive fungal disease is imperative in these patients, and longer survival can be achieved with early CT detection and prompt institution of high-dose antifungal therapy. MATERIAL AND METHODS: February, 1992 to December, 1994, sixteen cases of invasive pulmonary aspergillosis in AIDS patients were retrospectively reviewed. All patients underwent a chest radiograph and high resolution Computed Tomography (HRCT) and the results were confirmed by pathology. RESULTS: 11/16 cases (68.8%) showed angioinvasive aspergillosis, characterized by nodules surrounded by the halo sign and cavitations; the remaining 5 patients (31.2%) showed invasive aspergillosis of the airways with centrilobular nodules and/or peribronchial consolidations. Five cases of extrapulmonary fungal dissemination were also observed. CONCLUSIONS: HRCT is a sensitive noninvasive method for evaluating early angioinvasive aspergillosis because the halo sign is characteristic enough to allow an early presumptive diagnosis. Invasive aspergillosis of the airways presents no characteristic radiologic pattern. However, the association of the clinical and radiologic pattern allows prompt institution of high-dose antifungal therapy. PMID- 9972212 TI - [Magnetic resonance angiography of the epiaortic vessels of the thorax]. AB - INTRODUCTION: Magnetic Resonance angiography (MRA) is an accurate and non invasive diagnostic method to evaluate vascular disease. On the basis of its technological advancements, this technique has gained an important role in the diagnostic protocol of cerebral and cervical vascular diseases. Nonetheless, MRA efficacy changes in different anatomic districts as a consequence of the specific anatomy and flow features. Cardiac and respiratory artifact and different coil sensitivity also affect MRA results. For these reasons, intrathoracic epiaortic vessels are a difficult applications for MRA. MATERIAL AND METHODS: We examined 20 patients affected with epiaortic atherosclerosis with MRA, carried out with an 0.5 T MR unit (Vectra, GE). Examinations consisted of Phase Contrast (PC) 3D sequences (TR/TE/FA/Venc = 30/13/45/30-50), with 3 axes of flow encode, matrix 128 x 256, 2 mm partition thickness, and axial and/or coronal acquisition volume. The MRA was repeated after Gd-DTPA intravenous perfusion and a qualitative and quantitative evaluation of pre- and post-contrast results was performed. Specific parameters of evaluation were: angiographic contrast, contrast to noise ratio, saturation effect of longitudinal magnetization, contrast between arteries and veins. All patients were examined with Doppler US and angiography. MRA data were compared to angiography in order to establish MRA sensitivity and specificity. RESULTS AND CONCLUSIONS: PC sequences showed high accuracy in the examination of the proximal tract of epiaortic vessels; Gd-DTPA administration substantially improved MRA results. The perspectives of technological improvement will probably candidate PC MRA to be a valid alternative to US-Doppler and, perhaps, to angiographic study. PMID- 9972213 TI - [Budd-Chiari syndrome: retrospective study of 8 cases assessed with computerized tomography]. AB - PURPOSE: Budd-Chiari syndrome is a rare disease due to the obstruction of hepatic veins and, sometimes, of the inferior vena cava. The disease, whose etiopathogenesis is often unproven, may show acute or chronic clinical course with different features at pathology. We carried out a retrospective study of 8 consecutive patients with the Budd-Chiari syndrome to assess the diagnostic role of CT and to define the main patterns of the disease. MATERIAL AND METHODS: Our patient population consisted of 8 women with clinical and instrumental suspicion of Budd-Chiari syndrome. Three patients had acute and 5 chronic clinical presentation: the former had had acute symptoms right after delivery, while one of the latter was referred to oral contraceptive abuse, another was diagnosed 18 months after delivery and finally the cause was not known in the other 3 cases. CT was performed with contiguous slices (8 mm) of the upper abdomen, before and after i.v. contrast agent infusion. Liver images were always acquired 15-20 minutes after contrast agent administration. RESULTS: In the acute patients, CT showed increased liver volume, diffuse parenchymal hypodensity in unenhanced scans, except for some skip areas (segments I and IV, paracaval parenchyma) and strong postcontrast enhancement. Thrombosis of the suprahepatic veins was found in all patients and partial thrombosis of the inferior vena cava in one. Abundant peritoneal effusion was always found. In the chronic patients, CT showed caudate lobe and left lobe hypertrophy, mostly associated with right lobe hypo-atrophy. Moreover the hypertrophic areas showed bright and inhomogeneous contrast enhancement, with a reversed pattern at 15-20 minutes postcontrast. Thrombosis of the suprahepatic veins was found in 3 patients and partial thrombosis of the inferior vena cava in one. Peritoneal effusion was seen in 2 cases. CONCLUSIONS: The Budd-Chiari syndrome causes anatomical, morphological and volumetric changes in the hepatic parenchyma which are referrable to difficult venous flow and differ in acute vs chronic forms. CT permits to grade liver involvement by the organ's morphodensitometric changes, which are once again different in the acute vs the chronic disease. Moreover, thrombosis of suprahepatic veins and of the inferior vena cava and portal vein is often demonstrated. Therefore CT can be considered a valid diagnostic tool for use in the patients with suspected Budd Chiari syndrome together with B-mode and color Doppler US. PMID- 9972214 TI - [Triphasic spiral computerized tomography of the liver: vascular models of non cystic focal lesions]. AB - PURPOSE: The purpose of this study was to investigate if Triphasic Spiral CT (arterial, portal and equilibrium phases) can improve the characterization of noncystic focal lesions. MATERIAL AND METHODS: Sixty-six patients with suspected focal liver disease underwent Triphasic Spiral CT. After the injection of 120-140 ml contrast material at 3 ml/s the liver was imaged in the arterial (scanning delay: 20-27 s), portal (scanning delay: 45-80 s) and equilibrium (scanning delay: 5-8 min) phases. The enhancement of each lesion was evaluated in each phase and the lesions were grouped by enhancement pattern (11 patterns in all). The reference standards in our 66 patients were surgery (12), biopsy (43), MRI (9), follow-up (9), somatostatin receptor scintigraphy (6). RESULTS: One hundred and twenty-six liver lesions were detected in 66 patients, four of 11 enhancement patterns (hypo/hyper/hyper, hyper/iso/iso, hyper/hyper/iso, hyper/hyper/hyper) were always referrable to benign disease (hemangioma, focal nodular hyperplasia FNH-adenoma). Four of 11 enhancement patterns (iso/hypo/hypo, iso/iso/hypo, hyper/hypo/hypo, hyper/hyper/hypo) were always referrable to malignant disease (hepatocellular carcinoma-HCC-metastases). The other two patterns (hypo/hypo/hypo, hypo/hypo/hyper) were seen in both benign and malignant diseases. CONCLUSIONS: Triphasic Spiral CT improves the characterization of HCC, FNH, adenoma and hemangioma. The arterial and the equilibrium phases add no information to the yield of the portal venous phase in metastases, except for those from pancreas neuroendocrine tumors in the arterial phase. In our experience, patients with unclassified lesions at US or conventional CT, suspected HCC and metastases from pancreas neuroendocrine tumors should be submitted to Triphasic CT of the liver. This technique however does not appear to be indicated in the study of liver metastases from hypovascular tumors, while it improves the detection of FNH and adenoma. PMID- 9972215 TI - [Magnetic resonance pyelography: clinical use of ultrafast breath-hold sequences in obstructive uropathy. Personal experience]. AB - INTRODUCTION: We investigated the diagnostic yield of MR pyelography (MRP) performed with two ultrafast breath-hold sequences in obstructive uropathy patients. MATERIAL AND METHODS: Thirty-four patients with US demonstration of urinary tract dilation were examined with MRP at 1.5 T and with a standard body coil. HASTE sequences (TE 66, ETL 128, FA 180 degrees, 1 NEX, MA 240 x 256, slice thickness 4 mm, TA 13 s) were always performed and 26/34 patients were also examined with single-shot TSE sequences (TE 1100, ETL 240, FA 150 degrees, 1 NEX, slice thickness 7 cm, MA 240 x 256, FS, TA 7 s); 20/34 patients were given 500 mL superparamagnetic contrast agent (Lumirem). MRP findings were interpreted independently by two radiologists and analyzed for image quality, the presence/absence of dilation, the obstruction grade (mild, moderate, severe), site (intrarenal; ureteropelvic junction; proximal, mid-, distal ureter; indeterminate) and cause (intrinsic obstruction from a stone or other conditions; stenosis; indeterminate cause). The sensitivity, specificity, positive and negative predictive values for the detection of urinary tract dilation were calculated for each reviewer and interobserver agreement was calculated with the k analysis relative to the presence, grade, site and cause of urinary tract dilation. RESULTS: MRP examinations were considered technically adequate in all cases by both observers. As for the presence of urinary tract dilation, the values were 100% for the first observer and 97%, 100%, 100%, and 95%, respectively, for the second observer. Interobserver agreement was .98 for dilation presence (excellent), .80 for dilation degree (excellent), .62 for dilation site (good) and finally .69 for dilation cause (good). DISCUSSION AND CONCLUSIONS: MRP performed with the ultrafast breath-hold technique provides very good results in diagnosing urinary tract dilation, as well as the obstruction grade, site and cause, with results equal or even superior to those of non-breath hold sequences. Ultrafast MRP lasts only 10 minutes, meaning it occupies the magnet shortly and costs less: it can be thus considered a routine alternative to conventional diagnostic imaging, especially ivp, in the evaluation of obstructive uropathy. PMID- 9972216 TI - [A project for the organization and planning of a diagnostic ultrasonography area at a radiology department]. AB - PURPOSE: The increasing use of ultrasound (US) for both diagnostic and interventional procedures has not been supported yet by proper and adequate planning of dedicated rooms. Therefore we studied both the organization and the design of such areas. METHODS AND DISCUSSION: As for organization, we considered: a) the kind of examination performed; b) the main department activity (in /outpatients, diagnostic or interventional procedures); c) the schedule for each room by examination type and timing (patient preparation, actual examination and read-out times). As for room design, we studied the size and location of the diagnostic unit, dressing rooms, entrances and restrooms, as well as the furniture in general. We also studied the location of waiting rooms and corridors, the location and size of the read-out areas, and the room for post interventional monitoring, as well as all the details about microclimate and lighting. Then we designed two different modules with the relevant planimetry: one featuring two adjacent diagnostic rooms and the other featuring a single diagnostic room. Some ergonomic solutions are also proposed concerning the location of the US system relative to the stretchers entrance and the location of the post-interventional monitoring room relative to the radiologic room(s). Finally, we evaluated the size of some peculiar pieces of equipment of a radiologic room by their function. CONCLUSIONS: The functional arrangement of the diagnostic US unit and its space requirements, permits to optimize the use of the whole structure complying with the ergonomic criteria for operators and enabling the rapid throughout of patients with no waste of time. PMID- 9972217 TI - [Insertion and management of long-term central venous devices: role of radiologic imaging techniques]. AB - INTRODUCTION: Anticancer chemotherapy causes irreversible damage to the endothelial wall of small vessels. This is the reason why long-term (more than 3 months) central venous devices are essential to administer chemotherapy drugs to cancer patients and antibiotics for chronic or severe infections and in patients requiring long-term parenteral nutrition. We report our experience with the percutaneous implantation of central venous devices in a radiology department. MATERIAL AND METHODS: March, 1993, to August, 1997, eighty-seven consecutive patients (26 men and 61 women, mean age: 55 years) were examined. The indications for central venous catheter placement included anticancer chemotherapy in 82 cancer patients, repeated blood transfusion in one patient with bone marrow aplasia and nutritional support in four cancer patients. Eighty-four central venous devices (75 totally subcutaneous systems--Port-a-cath Dome--, and 9 partially tunneled catheters--Groshong) were inserted. The average follow-up was 6.5 months (range: 1-18). All procedures were performed in the radiology department and venous access was achieved with fluoroscopy using the Seldinger technique. Chest radiography with the patient standing was routinely performed after the procedure and repeated the day after to assess the catheter position and the presence of pneumothorax. The venous catheters were placed in the subclavian vein in 68 cases (12 in the right side and 56 in the left side), internal jugular vein in 12 cases (9 in the right side and 3 in the left side) and right femoral vein in 4 cases. We prefer the subclavian vein (80.9%) for better cosmetic results, wider catheter angulation and easier fixation to the deep plane. RESULTS: The first access failed in 6 cases (6.8%). A pneumothorax occurred in 4 patients (4.7%) and late complications were seen in 15 patients (17.8%) after a mean of 15.7 weeks (range: 2-48). Catheter-related infections developed in 6 patients (7.1%) after a mean of 20 weeks (range: 5-48). The microorganisms cultured from these catheters was the Staphylococcus epidermidis. After two weeks' specific antibiotic therapy, all the devices were removed. Deep venous thrombosis occurred only in one patient after 10 months and was successfully treated with direct thrombolytic infusion. The catheter was displaced in the right atrium in two patients after 11 and 12 weeks, respectively: both catheters were removed by transfemoral catheterization. CONCLUSIONS: The percutaneous implantation of--long-term central venous devices is a safe and tolerable procedure. In our experience, the radiology-assisted placement of these devices offers many advantages over surgical implantation. In particular, fluoroscopy allows direct visualization of the catheter position while insertion and positioning are essentially "blind" at surgery, which complicates venous access and increases the risk of catheter malpositioning. Radiologic follow-up is also useful to depict and correct complications. PMID- 9972218 TI - [Percutaneous needle biopsy guided with computerized tomography of the chest. Personal experience with 1,605 cases]. AB - INTRODUCTION: Fine-needle aspiration biopsy (FNAB) plays an important role in the diagnosis of lung diseases. We report the results of 1605 CT-guided chest biopsies performed September, 1992, to December, 1997, and introduce a new method for specimen storage and handling. MATERIALS AND METHODS: A lubricated flexible connection was placed between the needle and the syringe to cushion the improper movements transmitted on the needle by the operator during aspiration. 22-G needles were most frequently used. The pathologist's report included not only the presence/absence of tumor cells, but also the presence of suspicious/questionable cells, which latter finding led to another biopsy in 152 cases. RESULTS: 64.7% of the lesions were < or = 3 cm and 55.5% were < or = 2 cm. Pneumothorax occurred in 16.0% of cases and it required a chest tube in 5.0%. The specimens were not smeared on a slide but kept in a test tube and quickly sent to the pathologist. 84.3% of the specimens were adequate for diagnosis and special care was given to typifying microcytoma/non-microcytoma histotypes, because treatment is different. 1003 of 1313 cases (76.38%) were true positives, 192 (14.2%) true negatives, 101 (7.69%) false negatives and 17 (1.92%) false positives. Sensitivity was 90.85%, specificity 91.86% and diagnostic accuracy 91.01%. The positive and the negative predictive values were 98.3% and 65.5%, respectively. CONCLUSIONS: The use of a 60 mL syringe with a flexible connection reduces the rate of complications (eg, pneumothorax, bleeding) and also the biopsy time. It also improved the sampling accuracy, cushioning any possible inappropriate movement by the operator, and finally improved the material aspiration thanks to better vacuum than with the 20 30 mL syringes which are usually placed into biopsy guns. PMID- 9972219 TI - [Intravascular treatment of iliac aneurysms]. AB - INTRODUCTION: We investigated the feasibility of the intravascular treatment of iliac aneurysms in patients at high perioperative risk. MATERIAL AND METHODS: January, 1996, to December, 1997, seven iliac aneurysms in 5 patients were treated using endovascular procedures. The patients were 4 men and 1 woman whose mean age was 70 years (range: 61-74 years). Four of 7 aneurysms were in the common iliac artery (2 true aneurysms and 2 anastomotic aneurysms after aortoiliac bypass) and 3 were true internal iliac artery aneurysms. Preoperative CT and arteriography were performed in all cases to define the vascular morphology of the aneurysm, including its exact diameter and length. All procedures were performed in the operating room by a team of vascular radiologists and vascular surgeons, using a portable digital RX system (Philips BV29). The femoral approach was always used, which was percutaneous under local anesthesia in 4 cases and surgical under epidural anesthesia in the other 3 cases, according to the patient's general condition and to common femoral artery morphology. Six endovascular Passager grafts were positioned in the common iliac artery using over-the-wire techniques; platinum coil embolization of the aneurysmatic internal iliac artery had been performed in 2 cases. Coil embolization of the hypogastric artery aneurysm was the only treatment in 1 case. Bilateral aneurysms were treated separately, at intervals of no less than 3 months. RESULTS: Immediate aneurysm exclusion was obtained in all cases, as confirmed at 2-20 months' follow-up in 6 cases. A displaced prosthesis needed reoperation in 1 case. No complications were observed during or early after the procedures, which were always well tolerated by the patients. DISCUSSION: The endovascular treatment of iliac aneurysms is a relatively recent procedure and thus only short- and mid-run results are currently available, which appear satisfactory in 85% of the world's literature cases. Prosthesis displacement and intimal hyperplasia are reported as the main causes of failure. Lacking long-term results, we reserve this method to selected cases. Shorter hospitalization is another advantage. CONCLUSIONS: This little invasive procedure appears suitable for high-risk patients and in the aneurysmatic complications metachronous to surgical bypass. PMID- 9972220 TI - [Air bubble effect during alloy cooling in shielding blocks radiotherapy]. AB - INTRODUCTION: Shaped fields are widely used in radiotherapy to protect critical organs and to avoid unnecessary normal tissue irradiation. The most common system for photon beam shaping consists in a low melting point alloy. We studied the air bubbles which can occur during alloy cooling with both new and remelted alloys and when different cooling techniques are chosen. MATERIAL AND METHODS: Forty cone samples (18 of remelted alloy and 22 of new alloy) were prepared to evaluate the frequence of air bubble recurrence, with reproducible geometric sizes (height = 70 mm, major base surface diameter = 60 mm, minor base surface diameter = 40 mm). Air bubble sizes and dose inhomogeneity were evaluated by reproducing 60Co radiograph of each sample (two orthogonal projections: 6 x 7 cm). The samples were cooled at a constant temperature, following three different modalities: high (25 degrees C), medium (5 degrees C), low (-20 degrees C) temperature. Owing to the small geometrical magnification, air bubble sizes were determined by measuring their surface on samples lateral projections, taking into account the sight detectable bubble edges. RESULTS: Up to 300 mm2 lateral surface bubbles are always present in all castings. Casting inhomogeneities can produce a film density inhomogeneity ranging from 9% to 40%. The spatial distribution of bubbles seems to be random. CONCLUSIONS: Bubble recurrence is independent of both the metal alloy (repeatedly used castings) and the different block cooling modalities. The effect of air bubbles on the shielded areas dose inhomogeneity is generally of no relevant importance. However, these inhomogeneities can produce hot spots which must be taken into accurate consideration only in the particular treatments where critical small size organ dose sparing represents a basic issue (i.e. the shielding of eye lens). PMID- 9972221 TI - [Automated procedures for radiation protection and quality controls in conventional diagnostic radiology]. AB - To comply with regulations on radiation protection and quality controls is a difficult task when operating in large hospitals. This leads to the need of defining more efficient protocols and of making procedures as automated as possible. The procedure described in this paper is based on a multimeter controlled by a portable PC, and on a spreadsheet program for data processing. Multimeter data are automatically imported and processed, in order to assess the compliance of measured parameters with the reference regulations (IEC recommendations, radiation safety rules, etc.). The spreadsheet is permanently linked to a data base. It is therefore possible to perform the controls and to store the corresponding results in a shorter time (one hour per machine, approximately). By using a properly chosen quality index, monitoring the efficiency of the diagnostic equipment is also possible, which allows to prevent the onset of severe failures. PMID- 9972223 TI - [Intussusception of the right colon due to a colonic lipoma. Report of a case]. PMID- 9972222 TI - [Aggressive fibromatosis in the supraclavicular region: findings with computerized tomography and magnetic resonance in a case]. PMID- 9972224 TI - [Ileal angiolipoma in a patient with multisystemic manifestations of tuberous sclerosis: diagnosis with computerized tomography]. PMID- 9972225 TI - [A case of giant hepatic adenoma: ultrasonography and computerized tomography findings]. PMID- 9972226 TI - [Usefulness of ultrasonography in the diagnosis of torsion of Morgagni's hydatid: report of 4 cases]. PMID- 9972227 TI - [Calcified epithelioma of Malherbe: correlation of clinical characteristics, histologic findings and ultrasonography imaging of 4 cases]. PMID- 9972228 TI - [Umbilical veins]. PMID- 9972229 TI - The benefits and risks of n-3 polyunsaturated fatty acids. AB - There is a growing number of animal models and clinical trials of n-3 polyunsaturated fatty acid (PUFAs) supplementation in disease. Epidemiologic and biochemical studies have suggested beneficial effects of n-3 PUFAs. But also, the use of n-3 PUFAs has some potential toxicological risks that can be circumvented by careless processing, storing, and preserving the PUFAs. The use of n-3 PUFAs is safe if appropriate preparations and dosages are selected. Much research is needed to clarify their use under different disease conditions. The newly established clinical and nutritional facts on n-3 PUFAs will induce industry to develop food products based on this knowledge. PMID- 9972230 TI - Purification and characterization of a novel cold-regulated protein from an ice nucleating bacterium, Pseudomonas fluorescens KUIN-1. AB - The psychrotrophic ice-nucleating bacterium, Pseudomonas fluorescens KUIN-1 respond to a decrease in temperature with the induction of proteins that are classified as cold shock proteins (CSPs). We found the function of a 26-kDa protein of the CSPs in the strain KUIN-1. In strain KUIN-1, a cold shock from 18 to 4 degrees C induced the synthesis of the 26-kDa protein. By analysis with SDS PAGE, it was then demonstrated that the 26-kDa protein was produced by the cells after treatment at 4 degrees C. The 26-kDa protein was purified to apparent homogeneity by (NH4)2SO4 precipitation and some chromatographies (QA52, phenyl Superose, Superose 12, and Mono Q). The purified 26-kDa protein is composed of 6 subunits of 26.5-kDa with a molecular mass of approximately 159-kDa according to gel filtration and SDS-PAGE. The N-terminal sequence of the 26-kDa protein was Gln-Ala-Ala-Tyr-Tyr-Pro-Ala-His-His-His-Gln- Gln-Val-Gln-Gln-His-Trp-Gly-His-His . Specifically, 26-kDa protein of the CSPs of strain KUIN-1 was very effective in protecting the cold-labile enzyme, lactate dehydrogenase against denaturation by freezing. The characteristics of 26-kDa protein are analogous to the cold regulated protein of the plants. PMID- 9972231 TI - Nucleotide sequence of seed- and pollen-transmitted double-stranded RNA, which encodes a putative RNA-dependent RNA polymerase, detected from Japanese pear. AB - The nucleotide sequence of the largest double-stranded (ds) RNA (named dsRNA1) of three species of seed- and pollen-transmitted dsRNA species detected from Japanese pear was analyzed, and one strand was found to contain a single long open reading frame (ORF) of 1434 nucleotides that encoded a putative polypeptide containing 477 amino acid residues with a molecular mass of 54.9 kDa. This polypeptide contained amino acid sequence motifs conserved in putative RNA dependent RNA polymerases of RNA viruses. Attempts to visually identify or purify virus-like particles associated with the dsRNAs were unsuccessful. Slow sedimentation of the dsRNA fraction suggests that the dsRNAs may be unencapsidated. The concentration of dsRNAs in the host, Japanese pear, was about 16 times higher than that from a cryptic virus, radish yellow edge virus (RYEV). These results suggest that the dsRNAs were not from cryptic viruses. Partial nucleotide sequences of the two smaller dsRNAs (named dsRNAs 2 and 3) and two other dsRNAs (named dsRNAs 4 and 5) detected from only the Japanese pear cultivar (cv.) Akita Tazawa 3 Gou were analyzed, and encoded nearly the same amino acid sequence encoded by dsRNA1. PMID- 9972232 TI - Chitosanase activity of the enzyme previously reported as beta-1,3-1,4-glucanase from Bacillus circulans WL-12. AB - Chitosanases 33 kDa and 40 kDa in size were detected in the culture supernatant of Bacillus circulans WL-12. One of the two chitosanases, chitosanse 40 (40-kDa chitosanase) has been shown to be identical to the enzyme which has been reported previously as a beta-1,3-1,4-glucanase by Bueno et al. The enzyme has been classified into family 8 glycosyl hydrolases together with the enzymes formally known as cellulase family D. This enzyme named chitosanase 40/beta-1,3-1,4 glucanase hydrolyzed both chitosan and beta-1,3-1,4-glucan with similar efficiency. However, the production of the enzyme was induced with chitosan but not by beta-1,3-1,4-glucan. Therefore, it seems possible that the major substrate of this enzyme is chitosan rather than beta-1,3-1,4-glucan. Analysis of degradation products generated from partially N-acetylated chitosan showed that chitosanase 40/beta-1,3-1,4-glucanse hydrolyzes GlcN-GlcN and GlcN-GlcNAc linkages but not GlcNAc-GlcNAc nor GlcNAc-GlcN. The specificity for hydrolyzing linkages of this enzyme is similar to that of the chitosanase from S. griseus HUT6037. PMID- 9972233 TI - Thermal unfolding of the starch binding domain of Aspergillus niger glucoamylase. AB - A fragment of the starch-binding domain (SBDF) of Aspergillus niger glucoamylase was prepared using recombinant DNA techniques, and its thermal unfolding was investigated by high-sensitivity differential scanning calorimetry (DSC). Thermal unfolding of SBDF was found to be reversible at pH 7 as expected from a DSC study of the whole enzyme molecule [Tanaka A. et al., J. Biochem., 117, 1024-1028 (1995)] but not reversible at acidic region. Numerical analysis of the DSC curves showed that the denaturation was two-state, and some of the SBDF molecules were oligomeric (average degree of oligomerization was 1.2) at pH 7. It was suggested that the denaturation temperature of SBDF was lower than that of the starch binding domain in the whole enzyme molecule by about 4.5 degrees (decrease in the Gibbs energy change was 5.3 kJ mol-1) indicating a possibility that the starch binding domain is stabilized by glycosylation of the domain itself, or by the highly glycosylated linker region. PMID- 9972234 TI - Structural study on a sulfated polysaccharide-peptidoglycan complex produced by Arthrobacter sp. AB - The structure of a sulfated polysaccharide-peptidoglycan complex (SP-PG) produced by Arthrobacter sp. was analyzed by NMR spectroscopy. In addition, oligosaccharide fragments of the SP-PG-L obtained by HF degradation were analyzed by NMR spectroscopy. These findings indicated that the sulfated polysaccharide (SP) contains a repeating unit composed of two galactofuranosides and a glucopyranoside. The main chain of the trisaccharide is [-->6) beta-D-Galf(1-->6) beta-D-Galf(1-->ln, with beta-D-Glcp linked to one of the Galfs through a (1-->2) linkage. The sulfated positions of the trisaccharide were identified as C-3 and C 5 of the beta-glucosylated Galf residues, and C-2 or C-3 of the other Galf residue. PMID- 9972235 TI - Synthesis of 4-hydroxy-3(2H)-furanone acyl derivatives and their anti-cataract effect on spontaneous cataract rats (ICR/f). AB - 4-Hydroxy-2,5-dimethyl-3(2H)-furanone (HDMF) and 2(or 5)-ethyl-4-hydroxy-5(or 2) methyl-3(2H)-furanone (EHMF) are known to inhibit cataract development in spontaneous cataract rats (ICR/f). Forty-five acylated hydroxyfuranone derivatives were designed and synthesized for an anti-cataract test, and their hydrophobic constants were also tested. Among these derivatives, 2,5-dimethyl-4 pivaloyloxy-3(2H)-furanone (HDMF pivalate) exerted a marked protective effect against the development of cataract in a galactose-induced model using cultured rat lens (in vitro). When tested on an ICR/f cataract model (in vivo), HDMF pivalate showed more significant inhibition of cataract development than parent compound HDMF. This derivative is more lipophilic than HDMF, so that HDMF pivalate can penetrate the cornea more easily than HDMF. The inhibition of cataract development by HDMF converted from HDMF pivalate is supported by the fact that HDMF was observed in the lens of ICR/f rats treated with HDMF pivalate. PMID- 9972236 TI - Cloning, sequencing, and heterologous expression of rat methionine synthase cDNA. AB - Methionine synthase catalyzes cobalamin-dependent methyl transfer reaction from 5 methyltetrahydrofolate to homocysteine, forming methionine. Rat methonine synthase cDNA was cloned and analyzed by RT-PCR, 3'- and 5'-RACE techniques. The cDNA consists of a 0.3-kb upstream untranslated region, a 3.8-kb coding region, and a 0.4-kb downstream untranslated region. The open reading frame encoded a polypeptide of 1,253 amino acid residues with a calculated molecular weight of 139,162. This molecular weight was in good agreement with the observed one (143,000) of the purified rat liver enzyme. The deduced amino acid sequence was 53, 92, and 64% identical with those of the Escherichia coli, human, and presumptive Caenorhabditis elegans enzymes, respectively. All the fingerprint sequences, forming parts of the cobalamin- and S-adenosylmethionine-binding sites, were completely conserved in the rat methionine synthase. A high-level expression of catalytically active enzyme in insect cells was done by infection with a baculovirus containing the rat methionine synthase cDNA. PMID- 9972237 TI - Effects of carbohydrate chain on surface net charge and hydrophobicity of glycoenzymes. AB - Three different carbohydrate-depleted enzymes were prepared from an endo-beta-1,4 glucanase of Aspergillus niger IFO31125 by treatment with endo-beta-N acetylglucosaminidase or alpha-mannosidase. The molecular sizes of these enzymes decreased from 40 kDa containing about 8.9% carbohydrate to 39, 38, and 37 kDa with carbohydrate at 4.5, 1.3, and 0.8% (w/w), respectively. The surface net charges on these enzyme preparations were calculated from their electrophoretic mobilities measured by capillary zone electrophoresis. They had increased negative charges corresponding to the decreases in the carbohydrate content; those of native and 37-kDa enzymes were about -0.03 and -0.045, respectively. The surface hydrophobicities of proteins were also measured by partitioning the enzymes in a two-phase system containing polyethylene glycol and dextran, and decreased corresponding with decreases in their carbohydrate content. The results indicated that the high mannose type of carbohydrate chain in endo-beta-1,4 glucanase affected the surface net charge on the enzyme and increased the surface hydrophobicity. PMID- 9972238 TI - N2733, 1-[3-(3-pyridyl)-acryloyl]-2-pyrrolidinone hydrochloride inhibits LPS induced TNF-alpha production and improves survival in endotoxemic mice. AB - N2733, 1-[3-(3-pyridyl)-acryloyl]-2-pyrrolidinone hydrochloride, was examined for its effect on TNF-alpha production by human myeloid THP-1 cells stimulated with lipopolysaccharide (LPS). N2733 inhibited LPS-induced release of TNF-alpha from THP-1 cells with an IC50 of 11 microM. N2733 did not affect the cell viability at the concentration of 50 microM or 100 microM. This indicates that N2733 is a potent inhibitor for TNF-alpha production without severe cytotoxicity. N2733 was also studied in two murine endotoxin shock models induced with LPS. One model was DBA/2 mice injected with LPS (5.6 mg/kg, i.v.), which increased the serum level of TNF-alpha within 1 hr. Treatment of these mice with N2733 (100 mg/kg x 2, i.p.) decreased the serum level of TNF-alpha significantly. Another model was DBA/2 mice induced with LPS (30 mg/kg, i.v.), which reduced the survival rate to 30% during 7 days. Administrations of 30 mg/kg and 100 mg/kg N2733 (i.v.) restored the survival rates to 60% and 90% respectively. Our data demonstrate that N2733 inhibits LPS-induced TNF-alpha production, and this response is associated with an improvement in the survival rate of endotoxemic mice. PMID- 9972239 TI - Lithocholic acid side-chain cleavage to produce 17-keto or 22-aldehyde steroids by Pseudomonas putida strain ST-491 grown in the presence of an organic solvent, diphenyl ether. AB - We devised a method to screen for microorganisms capable of growing on bile acids in the presence of organic solvents and producing organic solvent-soluble derivatives. Pseudomonas putida biovar A strain ST-491 isolated in this study produced decarboxylated derivatives from the bile acids. Strain ST-491 grown on 0.5% lithocholic acid catabolized approximately 30% of the substrate as a carbon source, and transiently accumulated in the medium androsta-1,4-diene-3,17-dione in an amount of corresponding to 5% of the substrate added. When 20% (v/v) diphenyl ether was added to the medium, 60% of the substrate was converted to 17 keto steroids (androst-4-ene-3,17-dione-like steroid, androsta-1,4-diene-3,17 dione) or a 22-aldehyde steroid (pregna-1,4-dien-3-on-20-al). Amounts of the products were responsible for 45, 10, and 5% of the substrate, respectively. In the presence of the surfactant Triton X-100 instead of diphenyl ether, 40% of the substrate was converted exclusively to androsta-1,4-diene-3,17-dione. PMID- 9972240 TI - Structure-activity relationships of flavonoids and the induction of granulocytic- or monocytic-differentiation in HL60 human myeloid leukemia cells. AB - The flavones apigenin and luteolin strongly inhibited the growth of HL60 cells and induced morphological differentiation into granulocytes. The flavonol quercetin inhibited the cell growth and induced a differentiation marker, i.e., NBT reducing ability. However quercetin-treated cells were not morphologically differentiated into granulocytes. The chalcone phloretin weakly induced NBT reducing ability and a marker of monocytic differentiation alpha-naphthyl butyrate esterase activity in the cells. Quercetin and phloretin appeared to induce the differentiation of HL60 cells into monocytes. The proportion of alpha naphthyl butyrate esterase-positive cells induced by genistein was less than that of the NBT-positive cells. Some of the nuclei in genistein-treated HL60 cells morphologically changed. Genistein must have induced both granulocytic and monocytic differentiation of HL60 cells. The flavonols galangin and kaempferol, which had fewer hydroxyl group(s) in the B-ring than quercetin, and the flavanone naringenin inhibited the growth but did not induce the differentiation of HL60 cells. PMID- 9972241 TI - Substrate specificity of the alpha-L-arabinofuranosidase from Trichoderma reesei. AB - The precise substrate specificities of an alpha-L-arabinofuranosidase from Trichoderma reesei were investigated. The enzyme released arabinose at appreciable rates from p-nitrophenyl-alpha-L-arabinofuranoside, O-alpha-L arabinofuranosyl-(1-->3)-O-beta-D-xylopyranosyl-(1-->4) -D-xylopyranose (A1X2), arabinan, arabinoxylan, arabinogalactan, debranched-arabinan and gum arabic, but not from O-beta-D-xylopyranosyl-(1-->4)-[O-alpha-L-arabinofuranosyl-(1-->3)] -O beta-D-xylopyranosyl-(1-->4)-D-xylopyranose (A1X3) or O-beta-D-xylopyranosyl-(1- >2)-O-alpha-L-arabinofuranosyl -(1-->3)-O-beta-D-xylopyranosyl-(1-->4)-O-beta-D xylopyranosyl-(-->4) -D-xylopyranose (A1X4). The enzyme hydrolyzed methyl 2-O-, methyl 3-O- and methyl 5-O-alpha-L-arabinofuranosyl-alpha-L-arabinofuranosides to arabinose and methyl alpha-L-arabinofuranoside with the order of hydrolysis being: (1-->5)- > (1-->2)- > or = (1-->3)-linkages. The enzyme hydrolyzed the (1- >3)-linkage faster than the (1-->5)-linkage of methyl 3,5-di-O-alpha-L arabinofuranosyl-alpha-L-arabinofuranoside. The degree of conversion of arabinan and debranched-arabinan to monosaccharides by the enzyme was 33.0% and 9.1%, respectively. The alpha-L-arabinofuranosidase preferentially cleaved the arabinosyl side-chain from the arabinan rather than the terminal arabinosyl residue of the arabinan backbone. PMID- 9972242 TI - A novel ELISA format for the rapid and sensitive detection of staphylococcal enterotoxin A. AB - Staphylococcal food poisoning is one of the leading causes of bacterial food poisoning each year. Detection kits for staphylococcal enterotoxins are commercially available and the assays can require from one and a half to twenty four hours to complete with detection limits ranging from 0.5 to 2 ng enterotoxin per gram of food. We have successfully demonstrated a microsphere-packed capillary (MPC) ELISA for the detection of staphylococcal enterotoxin A (SEA) and have compared it to two commercially available kits. The MPC assay detected a lower amount of SEA in ham, chicken, cheese, and bean sprouts than either of the two commercially available kits. In addition, the novel MPC assay was completed in less than ten minutes, as compared to three and twenty-four hours for the two commercially available kits. This research also demonstrated that the MPC ELISA can contain integrated positive and negative controls and has the potential to simultaneously detect and identify multiple enterotoxins. PMID- 9972243 TI - Pectins in extracellular polysaccharides from a cell-suspension culture of Mentha. AB - Pectin constituents, which were about 70 w/w% of extracellular polysaccharides (ECP) from a cell-suspension culture of Mentha, were purified by gel filtration chromatography, and their sugar composition and linkage were investigated. Two major constituents identified were (1-->3)-linked galactan carrying arabinosyl residues on C-6 and (1-->4)-alpha-linked galacturonan partially interspersed with (1-->2)-linked rhamnosyl resides. Acetylated or methylated pectins were not identified on 1H-NMR analysis. PMID- 9972244 TI - Molecular cloning and analysis of a lipase gene from Pseudomonas fluorescens No. 33. AB - The gene encoding an extracellular lipase from Pseudomonas fluorescens No. 33 was cloned and sequenced. A single open reading frame consisting of 1,428 nucleotides that encoded a mature protein of 476 amino acids was recognized. Sequence analysis showed that the deduced molecular weight of 50,209 agreed with the molecular weight of the purified lipase as measured by SDS-PAGE and the lipase lacked a signal peptide. The presence of a repeating motif, GXXGXDXXX, suggested that the lipase might be exported and secreted via a system that involves the ATP binding cassette protein. PMID- 9972245 TI - Mutational analysis of the histidine-containing phosphotransfer (HPt) signaling domain of the ArcB sensor in Escherichia coli. AB - The Escherichia coli ArcB sensor is involved in anaerobic phosphotransfer signal transduction. ArcB is a hybrid sensor that contains three types of phosphotransfer signaling domains in its primary amino acid sequence, namely, transmitter (or His-Kinase), receiver, and histidine-containing phosphotransfer (HPt) domains. However, examination of the function of the newly-discovered HPt domain (named ArcBc) is still at a very early stage. To gain a general insight into the structure and function of the widespread HPt domains, on the basis of its three-dimensional crystal structure, in this study we constructed a certain set of mutants each having a single amino acid substitution in the HPt domain of ArcB. These ArcBc mutants were characterized and evaluated, based on the in vivo ability to signal the OmpR receiver via trans-phosphorylation. PMID- 9972246 TI - State of imidazole side chain of hen lysozyme modified with histamine and Japanese quail lysozyme. A study by immobilized metal ion affinity chromatography. AB - Hen lysozyme modified with histamine (HML) and Japanese quail lysozyme (JQL) were treated with immobilized metal ion affinity chromatography to analyze the states of their imidazole groups. When Ni(II) was used as the metal ion immobilized, JQL was strongly retained in a Ni(II)-chelating Sepharose column, while hen lysozyme and HML were hardly retained in the same column. All of these lysozymes have a histidine imidazole group at the 15th position, while JQL has an additional histidine imidazole group at the 103rd position and HML has an additional imidazole group covalently attached to Asp101. Thus, I concluded that the imidazole group at the 103rd position of JQL is exposed to the solvent and recognized by the metal ion, but that the imidazole group attached to Asp101 in HML is localized to a hydrophobic region and not recognized by the metal ion. PMID- 9972247 TI - Properties of alpha-mannosidase partially purified from the apple snail, Pomacea canaliculata. AB - Pomacea canaliculata alpha-mannosidase (260 kDa), composed of at least two isoforms with different pI, was partially purified. The activity was maximum at pH 4 and unaltered after incubation at 60 degrees C for 60 min. ZnCl2, CaCl2, NaCl, and SH-reagents increased the activity, while MnCl2 and EDTA inhibited it. The enzyme catalyzed the hydrolysis of alpha 1-2, alpha 1-3, and alpha 1-6 mannosidic linkages. PMID- 9972248 TI - Isolation and properties of glucose-1-phosphatase from mycelia of Pholiota nameko. AB - An acid phosphatase with a very high substrate specificity for glucose-1 phosphate was isolated for the first time from mycelia of Pholiota nameko. The molecular weight of the enzyme was estimated to be 31,000 on gel filtration and 35,000 on SDS-PAGE. The activity was inhibited by Cu2+, Hg2+, molybdate, and tartaric acid. The sequence of N-terminal 20 amino acid residues was analyzed. PMID- 9972249 TI - Evidence that a beta-1,4-endoglucanase secreted by Acetobacter xylinum plays an essential role for the formation of cellulose fiber. AB - Cellulose-producing Acetobacter xylinum has been known to secrete a cellulose hydrolyzing beta-1,4-endoglucanase (CMCax). When antibodies to recombinant CMCax were added to the culture medium, the formation of cellulose fiber was severely inhibited. Western blot analysis using the antibody showed that this enzyme was secreted into the medium even by a cellulose non-producing strain (Cel-). These results indicate that beta-1,4-endoglucanase in the medium plays a critical role in the formation of cellulose fiber by the microorganism. PMID- 9972250 TI - Effects of substitution of Val for Leu11 of ovine angiotensinogen on renin activity. AB - A mutant angiotensinogen, L11V, in which Val11 was substituted for Leu11 of ovine angiotensinogen was prepared to have the same scissile peptide bond as the human one. The mutation didn't vary Km and kcat of human renin for the ovine substrate, but decreased those of rat renin to one half and one fortieth, respectively. Distances between the P1' subsite of angiotensinogens and the 224th (human renin numbering) residue in the S1' subsite of renins were estimated by molecular modelings. The marked decrease in kcat of rat renin for L11V could be attributed to the elongated distance between Val11 of L11V and Val221 of rat renin. It was also suggested that the distance is the reason why the human substrate cannot be cleaved by heterologous renins. PMID- 9972251 TI - Effects of elution [correction of eution] conditions on the separation of calpastatin, mu- and m-calpain on DEAE-Sephacel chromatography. AB - A rapid stepwise measurement for the activities of calpastatin and mu- and m calpains was developed by using 2-stage elution at pH 8.5 and then 7.0. The activities of calpastatin, mu-calpain and m-calpain can be rapidly assayed following the separation on DEAE-Sephacel chromatography by a 2 stage elution with 90 mM NaCl (pH 8.5), and then by 200 and 300 mM NaCl in elution buffer (pH 7.0). No significant differences in the recovery of these proteinases and inhibitor was observed between stepwise gradient and linear gradient methods. PMID- 9972253 TI - Effects of tea infusions of various varieties or different manufacturing types on inhibition of mouse mast cell activation. AB - We investigated effects of various tea infusions on mast cell activation using mouse mast cells. Among various tea extracts, infusions from cultivar 'Benihomare' and Taiwan lineage strongly inhibited histamine release after Fc epsilon RI cross-linking. Among three types of tea (from cultivar 'Benihomare'), extract from oolong tea or black tea inhibited histamine release more strongly than green tea extract. Furthermore, 'Benihomare' oolong tea extract suppressed tyrosine phosphorylation of cellular proteins after Fc epsilon RI cross-linking, but polyvinyl polypyrrolidone treatment of the extract to remove phenolic compounds, weakened the suppressive effect. PMID- 9972252 TI - Antimicrobial activity of 4-hydroxybenzoic acid and trans 4-hydroxycinnamic acid isolated and identified from rice hull. AB - Two antimicrobial substances in rice hull were isolated and identified as 4 hydroxybenzoic acid and trans 4-hydroxycinnamic acid by LC-MS, and 1H- and 13C NMR. An evaluation of 50% inhibition of growth (IC50) revealed that the two substances had different inhibition profiles against various microorganisms. Most of the gram-positive and some gram-negative bacteria were sensitive to trans 4 hydroxycinnamic acid and 4-hydroxybenzoic acid at IC50 concentrations of 100-170 and 160 micrograms/ml, respectively. PMID- 9972254 TI - Identification of the orotidine-5'-phosphate decarboxylase gene and development of a transformation system in the yeast Saccharomyces exiguus Yp74L-3. AB - To investigate the uracil biosynthetic pathway of the yeast Saccharomyces exiguus Yp74L-3, uracil auxotrophic mutants were isolated. Using conventional genetic techniques, four mutant genes concerned in uracil biosynthesis were identified and denoted as ura1, ura2, ura3, and ura4. Mutations in the URA3 and URA4 genes were specifically selected with 5-fluoroorotic acid (5-FOA). Vector plasmids containing the URA3 gene and an autonomously replicating sequence (ARS) of S. cerevisiae produced sufficient amounts of Ura+ transformants from the ura4 mutant of S. exiguus. This fact indicates that the S. exiguus URA4 gene encodes orotidine-5'-phosphate decarboxylase (OMP decarboxylase) and demonstrates that vector plasmids for S. cerevisiae are also usable in S. exiguus. PMID- 9972255 TI - Tryptophan pyrolysis products, Trp-P-1 and Trp-P-2 induce apoptosis in primary cultured rat hepatocytes. AB - The cytotoxicity of heterocyclic amines, dietary carcinogens derived from cooked foods, to primary cultured rat hepatocytes was studied. A tryptophan pyrolysis product, 3-amino-1,4-dimethyl-5H-pyrido[4,3-b]indole (Trp-P-1) was the most cytotoxic of 11 compounds tested. Trp-P-1 was found to induce apoptosis as measured by morphological changes in nuclear chromatin and internucleosomal DNA fragmentation. 3-Amino-1-methyl-5H-pyrido[4,3-b] indole (Trp-P-2) showed a moderate apoptotic effect, and other compounds had a similar but weaker effect. PMID- 9972256 TI - Relationship between chemical structures and biological activities of triterpenoid saponins from soybean. AB - Saponins can be found in more than one hundred plant families and in some marine animals. However, chemical investigation of soybean (Glycine max L. Merrill) saponins has begun only as recently as the 1970s. Here we focus on the chemical structure, the content, and biological activity of soybean saponins in current studies. Especially, we focus on 2,3-dihydro-2,5-dihydroxy-6-methyl-4H-pyran-4 one (DDMP) conjugated saponins and define the chemical structure of this as a natural precursor of group B and E saponins. PMID- 9972257 TI - Purification and characterization of tert-butyl ester-hydrolyzing lipase from Burkholderia sp. YY62. AB - An intracellular novel lipase which can hydrolyze t-butyl octanoate (TBO) was purified to homogeneity from crude cell-free extracts of Burkholderia (formerly Pseudomonas) sp. YY62 with 9% overall yield. Seventy-four-fold purification was achieved by ammonium-sulfate precipitation, three consecutive open-column chromatographies (DEAE anion-exchange, Sepharose CL-6B gel-filtration, and the second DEAE anion-exchange columns), and two HPLCs (TSK G2000SWXL gel-filtration and phenyl 5PW hydrophobic interaction columns). Enzymes hydrolyzing p nitrophenyl acetate were separated into two peaks (peak I and II) on the hydrophobic HPLC, and only peak II was found to have TBO-hydrolyzing activity. The peak preparation showed a single band of 40 kDa on SDS-PAGE and a molecular mass of 39 kDa on gel-filtration under non-denatured conditions, indicating the monomeric nature of the TBO-hydrolyzing lipase. The lipase showed maximum activity at pH 7.0 and 28 degrees C. The N-terminal 15 amino acid residues were determined as Met-Asp-Phe-Tyr-Asp-Ala-Asn-Glu-Thr-Arg-His-Pro-Glu-Gln-Arg, which showed no homology to known proteins, suggesting that the purified enzyme may belong to a novel class of hydrolase. PMID- 9972258 TI - Molecular cloning and sequencing of two phospho-beta-galactosidase I and II genes of Lactobacillus gasseri JCM1031 isolated from human intestine. AB - Lactobacillus (Lb.) gasseri JCM1031, which is classified into the B1 subgroup of the Lb. acidophilus group of lactic acid bacteria, characteristically produces two different phospho-beta-galactosidases (P-beta-gal) I and II in the same cytosol as reported in our previous papers [Biosci. Biotech. Biochem., 60, 139 141, 708-710 (1996)]. To clarify the functional and genetic properties of the two enzymes, the structural genes of P-beta-gal I and II were cloned and sequenced. The structural gene of P-beta-gal I had 1,446 bp, encoding a polypeptide of 482 amino acid residues. The structural gene of P-beta-gal II had 1,473 bp, encoding a polypeptide of 491 amino acid residues. The deduced relative molecular masses of 55,188 and 56,243 agreed well with the previous value obtained from the purified P-beta-gal I and II protein, respectively. Multiple alignment of the protein sequence of P-beta-gal I and II with those of P-beta-gals from 5 microorganisms had 30-35% identity on the amino acid level, but those with phospho-beta-glucosidases from 5 microorganisms had the relatively high identity of about 50%. Considering that this strain grows on lactose medium and shows no beta-galactosidase activity, and that purified P-beta-gal I and II can obviously hydrolyze o-nitrophenyl-beta-D-galactopyranoside 6-phosphate (substrate), and also the conservation of a cysteine residue in the molecule, the P-beta-gal I and II were each confirmed as a novel P-beta-gal enzyme. PMID- 9972259 TI - Arginine enhances induction of T helper 1 and T helper 2 cytokine synthesis by Peyer's patch alpha beta T cells and antigen-specific mucosal immune response. AB - The effects of arginine on cell proliferation and subsequent T helper (Th) 1 and Th 2 cytokine synthesis by murine Peyer's patch (PP) Th cells in vitro and the influence of arginine on the induction of antigen-specific mucosal and systemic immune responses in vivo were examined. When the PP T cells were stimulated with the anti-alpha beta T cell receptor (TCR) antibody in the presence of different concentrations of arginine, a higher proliferative response was observed in the culture with an optimal concentration of arginine compared with that with a minimum amount of this amino acid. The concentration of cytokines in the supernatant, the number of cytokine-producing cells and the cytokine-specific mRNA expression of PP T cells were also increased in a dose-dependent fashion. Furthermore, when mice fed on an arginine-supplemented liquid diet were orally immunized with tetanus toxoid plus cholera toxin as a mucosal adjuvant, a higher level of antigen-specific fecal IgA was observed when compared with the response in mice fed on an arginine-free diet. Taken together, these results suggest that arginine enhanced antigen-specific mucosal immune response resulting from the supporting activation of cell proliferation and subsequent cytokine synthesis of PP Th cells. PMID- 9972260 TI - Transformation of the edible basidiomycete Lentinus edodes by restriction enzyme mediated integration of plasmid DNA. AB - We have used the restriction enzyme-mediated DNA integration (REMI) method to establish a transformation system in Lentinus edodes using the recombinant plasmid pLC1-hph, which contains the L. edodes transcriptional signals and an Escherichia coli hygromycin B phosphotransferase gene. Protoplasts of L. edodes were treated by the PEG transformation mixture containing 50 units of SalI, which cleaves pLC1-hph at a single site, yielding about 15 transformants per 2.5 micrograms of DNA. The conventional PEG transformation without SalI, however, yielded only 1.5 transformants per 25 micrograms of DNA. The optimal amount of SalI for increased transformation was 50 units. In the case of transformation with SphI, which cleaves the plasmid at one site, the optimal amount of the enzyme was 2.5 units. Southern blot analysis of the SphI-derived transformants suggested that 50% of the plasmid integrations were REMI events. PMID- 9972261 TI - Apoptosis induced by niacin-related compounds in HL-60 cells. AB - We have investigated whether niacin-related compounds act as inducers of apoptosis in HL-60 cells. In this study, we found that picolinic acid, dipicolinic acid, and isonicotinamide strongly induce apoptosis. After treatments with these compounds, apoptosis started within 4 h and was induced in about 50% of the cells within 8 h. These compounds induced apoptosis at 5-10 mM, but did not at 1 mM. An ICE-like protease inhibitor (Z-Asp-CH2-DCB) completely blocked the apoptosis, but a caspase-1 inhibitor (Ac-YVAD-CHO) and a caspase-3 inhibitor (Ac-DEVD-CHO) did not block the apoptosis, suggesting that other caspases have the critical roles in the execution process of apoptosis induced by niacin related compounds. PMID- 9972263 TI - Isolation of the creA gene from the cellulolytic fungus Humicola grisea and analysis of CreA binding sites upstream from the cellulase genes. AB - A carbon catabolite repressor gene, creA, was isolated from the cellulolytic fungus Humicola grisea by using a portion of the Trichoderma reesei cre1 gene as a probe. The deduced amino acid sequence predicts a zinc finger protein of 419 amino acids in length, and its zinc finger regions show high similarity with those of Aspergillus CreAs, T. reesei Cre1, and Saccharomyces cerevisiae MIG1. Northern blot analysis showed that the H. grisea creA gene was highly transcribed when the mycelia were grown on glucose-containing media, but the transcription of the H. grisea endoglucanase 1 gene (egl1) and the exoglucanase 1 gene (exo1) were repressed under these conditions. Results of binding assays with the maltose binding protein::CreA(1-166) fusion protein and the egl1 and the exo1 upstream regions showed that some 6-bp sites having an identical or similar sequence to the consensus sequence for CreA binding were protected from DNase I digestion. PMID- 9972262 TI - Alanine dehydrogenase from Enterobacter aerogenes: purification, characterization, and primary structure. AB - Alanine dehydrogenase [EC 1. 4. 1. 1] was purified to homogeneity from a crude extract of Enterobacter aerogenes ICR 0220. The enzyme had a molecular mass of about 245 kDa and consisted of six identical subunits. The enzyme showed maximal activity at about pH 10.9 for the deamination of L-alanine and at about pH 8.7 for the amination of pyruvate. The enzyme required NAD+ as a coenzyme. Analogs of NAD+, deamino-NAD+ and nicotinamide guanine dinucleotide served as coenzymes. Initial-velocity and product inhibition studies suggested that the deamination of L-alanine proceeded through a sequential ordered binary-ternary mechanism. NAD+ bound first to the enzyme, followed by L-alanine, and the products were released in the order of ammonia, pyruvate, and NADH. The Km were 0.47 mM for L-alanine, 0.16 mM for NAD+, 0.22 mM for pyruvate, 0.067 mM for NADH, and 66.7 mM for ammonia. The Km for L-alanine was the smallest in the alanine dehydrogenases studied so far. The enzyme gene was cloned into Escherichia coli JM109 cells and the nucleotides were sequenced. The deduced amino acid sequence was very similar to that of the alanine dehydrogenase from Bacillus subtilis. However, the Enterobacter enzyme has no cysteine residue. In this respect, the Enterobacter enzyme is different from other alanine dehydrogenases. PMID- 9972264 TI - Cloning, sequencing, high expression, and crystallization of the thermophile Thermus aquaticus glycerol kinase. AB - Glycerol kinase (EC 2.7.1.30) is a key enzyme of glycerol uptake and metabolism in bacteria. Using PCR, we amplified and cloned a glycerol kinase gene, glpK, from Thermus aquaticus. The complete gene has 1488 base pairs, coding for a protein of 496 amino acids with a predicted molecular weight of 54,814. The amino acid sequence deduced from T. aquaticus glpK was found to have identities of 97 and 81%, respectively, with those of Thermus flavus and Bacillus subtilis glpK genes. After overproduction in Escherichia coli, the expressed enzyme was easily purified to homogeneity by DEAE-Toyopearl chromatography. The purified enzyme has been crystallized by the hanging drop vapor diffusion method at 22 degrees C. Comparison of the amino acid sequence with that of the B. subtilis enzyme showed that Ser and Lys are replaced by Ala and Arg, as was seen in mesophile and thermophile enzymes. PMID- 9972265 TI - A novel glycerol kinase from Flavobacterium meningosepticum: characterization, gene cloning and primary structure. AB - A thermostable glycerol kinase (FGK) was purified 34-fold to homogeneity from Flavobacterium meningosepticum. The molecular masses of the enzyme were 200 kDa by gel filtration and 50 kDa by SDS-PAGE. The Km for glycerol and ATP were 0.088 and 0.030 mM, respectively. The enzyme was stable at 65 degrees C for 10 min and at 37 degrees C for two weeks. The enzyme gene was cloned into Escherichia coli and its complete DNA was sequenced. The FGK gene consists of an open reading frame of 1494-bp encoding a protein of 498 amino acids. The deduced amino acid sequence of the gene had 40-60% similarity to those of glycerol kinases from other origins and the amino acid sequence of the putative active site residue reported for E. coli GK is identical to the corresponding sequence of FGK except for one amino acid residue. PMID- 9972266 TI - Substrate specificity of 2-deoxy-scyllo-inosose synthase, the starter enzyme for 2-deoxystreptamine biosynthesis, toward deoxyglucose-6-phosphates and proposed mechanism. AB - A crucial enzyme in the biosynthesis of the 2-deoxystreptamine aglycon of clinically important aminocyclitol antibiotics is 2-deoxy-scyllo-inosose synthase (DOIS), which is responsible for the initial carbocycle formation of 2-deoxy scyllo-inosose (1) from D-glucose-6-phosphate (G-6-P) (2). To get more insight into the mechanism and substrate specificity, deoxy-D-glucose-6-phosphates (deoxy G-6-P) were chemically synthesized and subjected to the reaction with DOIS. The enzyme appeared to use 2-deoxy- and 3-deoxy-G-6-P as substrates, both of which were converted into the corresponding dideoxy-scyllo-inosose products, but 4 deoxy-G-6-P failed in cyclization by DOIS. These results clearly support the proposed reaction mechanism involving the initial oxidation at C-4 of the G-6-P substrate. Another implication is the potential use of DOIS for the preparation of useful dideoxyinososes. PMID- 9972267 TI - Cloning of the gene for inorganic pyrophosphatase from a thermoacidophilic archaeon, Sulfolobus sp. strain 7, and overproduction of the enzyme by coexpression of tRNA for arginine rare codon. AB - The gene encoding an extremely stable inorganic pyrophosphatase from Sulfolobus sp. strain 7, a thermoacidophilic archaeon, was cloned and sequenced. An open reading frame consisted of 516 base pairs coding for a protein of 172-amino acid residues. The deduced sequence was supported by partial amino acid sequence analyses. All the catalytically important residues were conserved. A unique 17 base-pair sequence motif was found to be repeated four times in frame in the gene, encoding a cluster of acidic amino acids essential for the function. Although the codon usage of the gene was quite different from that of Escherichia coli, the gene was effectively expressed in E. coli. Coexpression of tRNA(Arg), cognate for the rare codon AGA in E. coli, however, further improved the production of the enzyme, which occupied more than 85% of the soluble proteins obtained after removal of heat denatured E. coli proteins. PMID- 9972268 TI - Nutritional effects of a D-methionine-containing solution on AH109A hepatoma bearing rats. AB - The effects of a D-methionine-containing solution (DMCS) on the nutritional status of AH109A hepatomabearing rats receiving total parenteral nutrition were studied. The DMCS solution inhibited the decrease of transferrin in the plasma of tumor-bearing rats when compared with the effect of an L-methionine-containing solution. The survival time was also significantly prolonged in the DMCS-treated rats. These results indicate that DMCS had a beneficial effect on the malnutrition induced in tumor-bearing rats and would be a useful amino acid solution for the nutritional support of cancer patients. PMID- 9972269 TI - Analysis of the oligosaccharide units of xyloglucans by digestion with isoprimeverose-producing oligoxyloglucan hydrolase followed by anion-exchange chromatography. AB - A method for rapidly identifying six of the most commonly found xyloglucan oligosaccharide units, XXXG, XLXG, XXLG, XLLG, XXFG, and XLFG was developed by high-performance anion exchange chromatography (HPAEC) with pulsed amperometric detection (PAD) before and after digestion with purified isoprimeverose-producing oligoxyloglucan hydrolase (IPase). Using this method, the compositions of oligosaccharide units of soybean and mung bean xyloglucans were re-examined. Significant amounts of oligosaccharides that have not previously been reported to be oligosaccharide units of soybean and mung bean xyloglucans were found. PMID- 9972270 TI - Cloning of genomic DNA of Rhizopus niveus lipase and expression in the yeast Saccharomyces cerevisiae. AB - Genomic DNA encoding Lipase I was cloned from Rhizopus niveus strain IFO4759. For expression of this gene in S. cerevisiae, DBY746 was transformed with YEp352PLipS, which had the cloned lipase gene under the control of a PGK promoter. This strain secreted the lipase at a high level (350 U/ml). The strain ND-12B was produced by a mating of DBY746, harboring YEp352PLipS, and NA74-3A, and dissection of asci. This new strain secreted the lipase up to 530 U/ml. Moreover, the lipase was produced most effectively in a medium containing Bacto yeast extract, soy-peptide, and sucrose. PMID- 9972271 TI - Gassericin A; an uncommon cyclic bacteriocin produced by Lactobacillus gasseri LA39 linked at N- and C-terminal ends. AB - Gassericin A, a bacteriocin that was produced by Lactobacillus gasseri LA39, was treated with lysylendopeptidase and 3-bromo-3-methyl-2-(2-nitrophenyl-mercapto) 3H-indole. The fragments were recovered by SDS-PAGE and sequenced. All amino acids of gassericin A were distributed by sequence analysis and the bacteriocin did not contain any modified amino acids. The amino acid sequence of gassericin A completely coincided with that found through the cloning of the structural gene. Gassericin A was shown to be a cyclic bacteriocin (class II) which is bound at the N- and C-terminal ends. This is the first example of a cyclic bacteriocin from lactobacilli lactic acid bacteria. PMID- 9972272 TI - Inhibition by a capsaicin antagonist (capsazepine) of capsaicin-induced swimming capacity increase in mice. AB - We investigated the endurance swimming capacity of mice injected with CAP antagonist (capsazepine). The increase of endurance swimming capacity by the administration of CAP was significantly suppressed by the injection of capsazepine. At the same time, serum adrenaline secretion, which was induced by CAP, was depressed by capsazepine. These findings suggested that the increase in endurance swimming capacity by CAP was mediated by the CAP receptor. PMID- 9972273 TI - Cloning and nucleotide sequence of the gene encoding a serine proteinase inhibitor named marinostatin from a marine bacterium, Alteromonas sp. strain B-10 31. AB - The gene (mstI) encoding a serine proteinase inhibitor named marinostatin from marine Alteromonas sp. strain B-10-31 was cloned and its nucleotide sequence was analyzed. A short open reading frame of 192 bp encoded 63 amino acids with a molecular weight of 6,985. Furthermore, the initial product of marinostatin (marinostatin L) was purified and its amino acid sequence was analyzed. These results indicate that marinostatin is produced as a unique precursor consisting of the mature peptide and the leader peptide for an ATP-binding cassette (ABC) transporter, and furthermore the initial product of marinostatin is dehydrated and processed by proteolysis to give homologous forms of marinostatin. PMID- 9972274 TI - New antibacterial diterpenoids from the Sarcodon scabrosus fungus. AB - The structures of new antibacterial diterpenoids that had been isolated from Sarcodon scabrosus were established by chemical and spectral means to be sarcodonin L (2) and M (3), both having the cyathane skeleton. Other antibacterial compounds were identified to be allocyathin B2 (1), sarcodonin G (4) and sarcodonin A (5) by comparing their spectral data with those of authentic samples. PMID- 9972275 TI - Compilation of mRNA sequences surrounding the AUG translation initiation codon in the green alga Chlamydomonas reinhardtii. AB - Sequences of 118 mRNAs of the green alga Chlamydomonas reinhardtii in the GenBank data base were compiled to examine the consensus sequence surrounding the AUG translation initiation codon. The consensus sequence for C. reinhardtii was found to be gc(A/C)A(A/C)(A/C) AUGGC. The AUG context of chloroplast proteins (nuclear coded) and non-chloroplast proteins were compared by a separate compilation, and some distinctive features in AUG context of chloroplast proteins were found. PMID- 9972276 TI - Synthesis of a novel phosphate ester of a vitamin E derivative and its antioxidative activity. AB - A novel phosphate ester containing a chromanol structure was synthesized from 1,2 diacyl-sn-glycero-3-phospho-2'-hydroxyethyl-2',5',7',8'-tetramethyl- 6' hydroxychroman (PCh) by hydrolysis catalyzed by phospholipase C from Bacillus cereus. The structure of the product was found by spectral analyses to be 2 (2',5',7',8'-tetramethyl-6'-hydroxychromanyl)ethylphosphate++ + (Ch-P). Ch-P was highly soluble in the aqueous phase at neutral pH values and exerted higher antioxidative activity than alpha-tocopherol and PCh in the Fe(III)/ascorbic acid catalyzed peroxidation of a fish oil emulsion and the autoxidation of a rat brain homogenate. PMID- 9972277 TI - Structural analysis of xyloglucan oligosaccharides by the post-source decay fragmentation method of MALDI-TOF mass spectrometry: influence of the degree of substitution by branched galactose, xylose, and fucose on the fragment ion intensities. AB - Highly branched xyloglucan oligosaccharides were analyzed by the post-source decay (PSD) fragmentation method of matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOFMS). The ratio of [M-Xyl]+ and [M Gal]+ fragment ion intensities could be used to characterize the degree of Gal substitution at the non-reducing end, because the number of possible chemical species was directly related to their relative ion intensity. The intensity of the [M-Fuc]+ ion was predominantly strong in the fragment spectrum of fucosyl oligosaccharides as the first fragmentation, indicating the fucosyl linkage to be much weaker than the other glycosidic linkages in the MALDI-PSD fragmentation. Setting fragment ion [M-Fuc]+ to the pseudo precursor ion [MF]+, the second fragmentation ions were produced from [MF]+ in the drift region in PSD fragmentation of fucosyl oligosaccharides. PMID- 9972278 TI - Identification of a structural gene encoding a metallothionein-like domain that includes a putative regulator protein for Streptomyces protease gene expression. AB - An open reading frame (termed ORF-PR) encoding a metallothionein-like domain including protein was found upstream of a previously identified Streptomyces chymotrypsin-type protease gene (sam-P20). Promoter and terminator activities of ORF-PR were detected using the promoterless Streptomyces tyrosinase gene as a reporter gene and expression of ORF-PR was supposed to occur before that of sam P20 gene. Frameshift mutation analysis showed that the ORF-PR product might act as a repressive regulator of the sam-P20 gene. PMID- 9972279 TI - Some of my not so favorite things about insulin and insulin-like growth factors in fish. AB - Several topics concerning insulin and IGFs rarely discussed among comparative physiologists/endocrinologists are reviewed. The topics addressed include interpretation of radioimmunoassays for insulin and IGFs, the major sites of synthesis of these peptides, signal transduction via peptide-specific, and possibly via related peptide receptors. Finally, some thoughts are included on the development of the insulin superfamily of peptides in two phyletic lines of evolution, proto- and deuterostomian animals. The author considers all the above topics open to further exploration. If this review initiates more discussion leading to unorthodox input to the field, its goal is achieved. PMID- 9972280 TI - (Pro)insulin and insulin-like growth factor I complementary expression and roles in early development. AB - Evidence that the insulin-like growth factors play a role in embryonic as well as postnatal growth and central nervous system development has accumulated recently from studies using knock-out mice models. However, no effects of IGF-I and II have been demonstrated prior to organogenesis in these studies. We summarize here results supporting the role of insulin (or its precursor proinsulin) in vertebrate development prior to the expression of IGFs. (Pro)insulin mRNA is expressed in the chick embryo during neurulation and early organogenesis and its inhibition by antisense oligodeoxynucleotides increase apoptosis. In another system, proliferative neuroretina, (pro)insulin expression predominates over IGF I expression. Modulation of apoptosis by (pro)insulin in retina may be largely responsible for the observed stimulation of DNA synthesis and neuronal differentiation. These effects are elicited as well by IGF-I, expressed later in neuroretina. Thus, these polypeptides have complementary expression in early embryos which suggests coordinated actions during development. PMID- 9972281 TI - Insulin-like growth factor-I receptor signal transduction: at the interface between physiology and cell biology. AB - The insulin-like growth factor-I receptor (IGF-IR) mediates the biological actions of IGF-I and IGF-II. The IGFs play a critical role in promoting development, stimulating growth and organogenesis via mitogenic, antiapoptotic and chemotactic activity. Recent research has focused on the events that occur intracellularly upon receptor activation. Several pathways have been shown to be important. The insulin-receptor substrate (IRS), SHC, GRB2, CRKII and CRKL adaptor proteins have all been implicated in transmitting signals to the nucleus of the cell. This review outlines some of the signalling pathways believed to be important in converting IGF-IR activation into changes in cell behavior and metabolism. PMID- 9972282 TI - Evolution of insulin-like growth factor-I (IGF-I) action: in vitro characterization of vertebrate IGF-I proteins. AB - While there is considerable structural evidence that IGFs share a long evolutionary history, less is known about the conservation of IGF action. These studies have primarily been hampered by the small amounts of purified IGFs that have been available for testing. More recently, however, we have adopted recombinant strategies to produce milligram quantities of IGFs for biological studies. Thus we have been able to compare the properties of rat, kangaroo, chicken, salmon and barramundi IGF-I, proteins that differ from human IGF-I by 3, 6, 8, 14 and 16 amino acids respectively. While we have found that the IGF-I proteins exhibit similar biological activities and type-I IGF receptor binding affinities, regardless of whether mammalian, avian or piscine cell lines are used, there was a trend suggesting that the fish proteins at least, were most effective in studies using homologous systems. Thus, salmon IGF-I was not as potent as human IGF-I in bioassays in mammalian cells, but was as effective as human IGF-I in piscine cells. As expected, the IGF-I proteins competed poorly for binding to type-2 receptors present on ovine placental membranes. Interestingly however, the two fish IGF-I proteins exhibited greater affinity for this receptor than the other IGF-I proteins, hence reminiscent of the results previously found with recombinant hagfish IGF. Despite these small differences, these results taken together indicate that the IGF-I proteins appear to have been remarkably conserved in both structure and in vitro action during vertebrate radiation. PMID- 9972283 TI - Glucagon-like peptide-1 activates the adenylyl cyclase system in rockfish enterocytes and brain membranes. AB - Glucagon-like peptide (GLP) exerts important physiological functions in fish liver, but extrahepatic sites of action and physiological roles have been largely ignored. We show here that GLP activates adenylyl cyclase in isolated brain and enterocyte membranes and increases cellular cyclic adenosine monophosphate (cAMP) levels in isolated enterocytes of rockfish (Sebastes caurinus). Following exposure to synthetic zebrafish GLP (zf-GLP) (1 nM-1 microM), a concentration dependent increase in enterocyte cAMP is noted. The maximum increase in cAMP levels is observed at 1 microM zf-GLP, and represents a 30% increase above control values. Exendin-4, a GLP receptor agonist in mammals, elicits a similar concentration-dependent increase in enterocyte cAMP. In contrast, norepinephrine or prostaglandin E2 (at 1 microM) increased cAMP levels by 2 and 4-fold, respectively. Brain membrane adenylyl cyclase is activated 20-40% by zf-GLP, and to a smaller extent by zf-glucagon, while exendin-4 is as effective as zf-GLP at a dose of 100 nM. These results suggest potential physiological roles of GLP in brain and intestine in piscine systems analogous to GLP-1 functions in these tissues described for mammals. PMID- 9972284 TI - Insulin-family peptide-receptor interaction at the early stage of vertebrate evolution. AB - This is an overview of our studies on insulin and insulin-like growth factor-I (IGF-I) interactions with their own and each other's receptors in the lamprey (Lampetra fluviatilis L.), an extant representative of the ancient vertebrate group of Agnathans as compared to mammal (rat). Lamprey insulin receptor shows species specificity, namely, it binds its own insulin with higher affinity than mammalian hormone. Nevertheless, and unlike mammalian insulin receptor, lamprey receptor discriminates relatively poorly between insulin and IGF-I. Autophosphorylation patterns are identical for both receptors. In contrast, IGF-I receptors in lamprey tissues are very similar to mammalian IGF-I receptors confirming known evolutionary conservatism of IGF receptor system. Presumed common evolutionary origin of insulin and IGF-I receptors and poor ability of lamprey insulin receptor to discriminate between two ligands, implies that lamprey insulin receptor is closer to putative ancestral protein that IGF-I receptor. Contrary to the common belief, ambient temperatures for lampreys (4-15 degrees C) put no constraints on either downregulation of receptors or the endocytosis of hormone-receptor complexes. PMID- 9972285 TI - Inhibition of flagellar motility of demembranated fowl spermatozoa by protease substrates. AB - We investigated the effects of various protease substrates on the motility of demembranated fowl spermatozoa. In the presence of ATP, the motility of demembranated spermatozoa was vigorous at 30 degrees C, but decreased markedly following the addition of protease substrates, such as N alpha-carbobenzoxy-L-lys thiobenzyl ester (BLT), N-benzoyl-phe-val-arg p-nitroanilide or N alpha-benzoyl D,L-arg p-nitroanilide (BAPNA) in a dose-dependent manner, within the range 0-1 mM. The subsequent addition of 100 ng/ml trypsin released the inhibitory effect of protease substrates within 10 s. Phosphorylation or dephosphorylation of several proteins of demembranated spermatozoa was observed following the addition of protease substrates, however, no consistent patterns of protein phosphorylation or dephosphorylation were associated with the inhibition of motility. These results suggest that endogenous protease activity is instrumental in the maintenance of fowl sperm motility and that the site of action of this protease is in the axoneme and/or accessory cytoskeletal components. This enzyme may not act directly on the phosphorylation of sperm proteins involved in the regulation of motility. PMID- 9972286 TI - Metabolic effects of oxalate in the perfused rat liver. AB - The effects of oxalate on the metabolism of the isolated perfused rat liver were investigated. The main purpose was to verify if oxalate is also active in intact organs as demonstrated in isolated cells. The results revealed that the action of oxalate in the perfused liver resembles only partially that observed in isolated hepatocytes. In the perfused liver, oxalate inhibited gluconeogenesis from alanine, pyruvate and lactate, inhibited glycolysis and stimulated glycogenolysis. These observations confirm previous measurements with isolated hepatocytes. However, additional effects, not observed in isolated hepatocytes, were found. In the perfused liver, oxalate stimulated glucose production from dihydroxyacetone, glycerol or sorbitol. Moreover, the effects of oxalate in the perfused rat liver occurred at concentrations well above those reported for isolated hepatocytes, revealing that the compound is less toxic in the intact tissue. In vivo, the metabolic effects reported here can only be expected to occur at supra-physiological concentrations of oxalate, as in the case of a chronic renal failure. PMID- 9972287 TI - Effect of carbohydrates upon insulin secretion in Bufo arenarum (Amphibia:Bufonidae). AB - Pancreas pieces of Bufo arenarum were incubated with several sugars at basal and stimulatory concentrations, and with inhibitors of their metabolism, measuring the insulin released by radioimmunoassay. Glucose, mannose, fructose, glyceraldehyde and dihydroxyacetone all at 8 mM, significantly enhanced the release of insulin elicited by basal concentrations of these carbohydrates (2 mM). The nonmetabolizable sugars galactose and 2-deoxyglucose failed to enhance insulin secretion. N-Acetyl-glucosamine at 8 mM did not significantly affect the release of insulin. D-Glucose, but not L-glucose, at 8 mM stimulated insulin secretion above baseline (2 mM glucose). At 8 mM, the D-glucose alpha-anomer significantly increased insulin release, while this effect was not observed using the beta-anomer. Insulin release elicited by 2 mM of the alpha-anomer was significantly higher than that triggered by the beta-anomer. Iodoacetate (5 mM), and dinitrophenol (0.3 mM) exerted an inhibitory effect upon glucose-induced insulin secretion. The effect of these carbohydrates and metabolic inhibitors- tested for the first time in amphibians--was similar to that described in the mammalian pancreas, thus suggesting that such compounds play an important role in the metabolic control of insulin secretion in amphibians. PMID- 9972288 TI - A myoglobin evolved from indoleamine 2,3-dioxygenase, a tryptophan-degrading enzyme. AB - The distribution, isolation, spectral and oxygen-binding properties, stability of ferrous state (autoxidation), amino acid sequence and gene structure of indoleamine 2,3-dioxygenase (IDO)-like myoglobins are summarized, and their evolution is discussed. Although it has long been thought that all hemoglobins and myoglobins have evolved from a common ancestral gene encoding a 14-16 kDa polypeptide, the discovery of IDO-like myoglobin from several gastropod molluscs clearly indicates that there was an alternative pathway for myoglobin evolution. PMID- 9972289 TI - Molecular cloning, sequence analysis and expression distribution of rainbow trout (Oncorhynchus mykiss) cystatin C. AB - Cystatin C is one of a family of proteinase inhibitors of cathepsins and other cysteine proteinases. Among warm-blooded vertebrates, small functional regions of cystatin amino acid sequences are well conserved among species, but major portions of cystatin amino acid sequences vary evolutionarily. Although considerable attention has been given to mammalian and avian cystatins, little data exist on cystatins from other vertebrates. A cDNA clone for trout cystatin C was isolated from a lambda gt11 cDNA library of rainbow trout (Oncorhynchus mykiss) liver. An apparently full-length cDNA clone of 674 bp encoding 132 amino acid residues was obtained. Sequence analysis indicated that trout cystatin C contains an N-terminal signal sequence extension of 21 amino acids and a mature sequence of 111 amino acid residues, with amino acid residues conserved in functional regions relative to mammalian and avian cystatin C. Using cloned cDNA as a probe, we investigated expression of the cystatin C gene in trout tissues, several cell lines of trout liver or liver tumor, and cell cultures of liver tumor origin. Cystatin C mRNA was in high abundance in trout embryo tissue, a tumor-derived liver cell line and some normal adult tissues. Southern hybridization analysis indicated one copy of the trout cystatin C gene per haploid genome, and sequence comparisons indicated considerable divergence in large portions of the coding region of the trout cystatin C gene relative to a variety of species. PMID- 9972290 TI - Disassembly of genome of higher eukaryotes: pulsed-field gel electrophoretic study of initial stages of chromatin and DNA degradation in rat liver and thymus nuclei by VM-26 and selected proteases. AB - Nuclei were treated with VM-26, topoisomerase II inhibitor, or exogenous proteases. Initial stages of multi-step chromatin degradation were analyzed by pulsed-field gel (PFG) electrophoresis. VM-26 induced the total genome breakdown into discrete chromatin fragments containing 0.3 Mbp DNA. Treatment of nuclei with recombinant cathepsin B and chymotrypsin also revealed 0.3-Mbp DNA fragments which were mediated by endonucleolysis. Longer incubation of nuclei with chymotrypsin exhibited the appearance of 0.05-Mbp DNA fragments and their oligomers. Proteases might trigger the detachment of chromatin from nuclear matrix and contribute to the release or activation of the endonucleolytic activity leading to the initial degradation of the DNA into high-molecular weight fragments. The fragments observed correspond in size to the suggested chromatin higher-order structures. The presented data imply that the initial stages of chromatin degradation represents in reality the genome disassembly into two basic units of genome topology--0.3-Mbp DNA chromatin loop-domains which are presumably the bits of biological information, and fundamental 0.05-Mbp DNA loopsize units which might generate the functional loops of different sizes. PMID- 9972291 TI - Amino acid sequence of the D-galactose binding lectin II from the sponge Axinella polypoides (Schmidt) and identification of the carbohydrate binding site in lectin II and related lectin I. AB - The sponge Axinella polypoides contains several D-galactose binding lectins. One of the main components, lectin I was sequenced earlier, the complete sequence of the other major constituent of saline extracts, lectin II has been determined by amino acid sequencing and mass spectrometry. Both lectins have a homology of 65% to each other and both possess a disulfide loop between positions 4 and 46. As long as this loop is closed in both lectins, they can be boiled in the presence of SDS or treated with 6 mol guanidine hydrochloride without losing their hemagglutinating activity. Incubation with beta-mercaptoethanol alone does not effect the carbohydrate binding capacity either. However, reduction of the disulfide bond under chaotropic conditions destroys the activity irreversibly. This disulfide loop is also an immunologically dominant epitope in both lectins, as was revealed with monospecific polyclonal antisera. Thus, sponge lectins seem to be of different origins, since three completely different structures were described: the structure of Geodia cydonium, related to the mammalian S-type lectins with one SH-group, the Axinella lectins with one disulfide loop and the Aaptos lectins I and II with 11 cysteine residues/subunit. PMID- 9972292 TI - The hemolymph clottable proteins of tiger shrimp, Penaeus monodon, and related species. AB - A clottable protein was purified from the hemolymph of tiger shrimp (Penaeus monodon) by sequential DEAE anion-exchange chromatography. The protein formed stable clots in the presence of Ca2+ and the transglutaminase in hemocyte lysate. It is thermostable at temperatures up to 66 degrees C. The molecular mass of the clottable protein was determined to be 380 kDa by SDS-PAGE and MALDI-TOF mass spectrometry, and the protein exists as disulfide-linked homodimers and oligomers. The size and amino acid composition of the clottable protein are similar to those of several other shrimps, prawns, lobster and crayfish, and their N-terminal amino acid sequences are 60-80% identical. Monosaccharide analysis of the clottable protein revealed the presence of mannose, glucosamine or N-acetylglucosamine and possibly glucose in this glycoprotein of about 5% sugar content. Lipid in the protein upon electrophoresis was hardly detectable with the Oil Red O staining method. In immunodiffusion and immunoblotting analyses, the anti-clottable protein antibodies reacted with the clottable proteins from the penaeid shrimps but not with those from other crustaceans. PMID- 9972294 TI - Contribution of mitochondria and peroxisomes to palmitate oxidation in rat and bovine tissues. AB - Total and peroxisomal palmitate oxidation capacities and mitochondrial enzyme activities were compared in tissues from growing rats, preruminant calves and 15 month-old bulls. Total palmitate oxidation rates were 1.9-5.2-fold higher in rat than in bovine tissues and 1.7-fold higher in the heart and muscles from calves than from growing bulls. The peroxisomal contribution to palmitate oxidation was similar between rats and bovines (i.e. calves and bulls) in liver (35-51%), heart (26%) but not in muscles (14 +/- 3% in rats vs 33 +/- 4.5% in bovines, P < 0.05). Mitochondrial enzyme activities were 1.8-4.8-fold higher in rat than in bovine tissues but the citrate synthase to cytochrome-c oxidase ratio was the highest in the liver (17-38), intermediate in the heart and muscles from calves and rats (6 10) and the lowest in heart and muscles from bulls (2-3, P < 0.05). In all tissues and animal groups, palmitate oxidation rates were similar per unit cytochrome-c oxidase activity, but not always per unit citrate synthase activity. Therefore, differences in mitochondrial contents (as between rats and bovines) or in mitochondrial characteristics (as between liver and muscles) relate to the differences in palmitate oxidation capacity. PMID- 9972293 TI - Black widow spider alpha-latrotoxin: a presynaptic neurotoxin that shares structural homology with the glucagon-like peptide-1 family of insulin secretagogic hormones. AB - alpha-Latrotoxin is a presynaptic neurotoxin isolated from the venom of the black widow spider Latrodectus tredecimguttatus. It exerts toxic effects in the vertebrate central nervous system by depolarizing neurons, by increasing [Ca2+]i and by stimulating uncontrolled exocytosis of neurotransmitters from nerve terminals. The actions of alpha-latrotoxin are mediated, in part, by a GTP binding protein-coupled receptor referred to as CIRL or latrophilin. Exendin-4 is also a venom toxin, and it is derived from the salivary gland of the Gila monster Heloderma suspectum. It acts as an agonist at the receptor for glucagon-like peptide-1(7-36)-amide (GLP-1), thereby stimulating secretion of insulin from pancreatic beta-cells of the islets of Langerhans. Here is reported a surprising structural homology between alpha-latrotoxin and exendin-4 that is also apparent amongst all members of the GLP-1-like family of secretagogic hormones (GLP-1, glucagon, vasoactive intestinal polypeptide, secretin, pituitary adenylyl cyclase activating polypeptide). On the basis of this homology, we report the synthesis and initial characterization of a chimeric peptide (Black Widow GLP-1) that stimulates Ca2+ signaling and insulin secretion in human beta-cells and MIN6 insulinoma cells. It is also reported here that the GTP-binding protein-coupled receptors for alpha-latrotoxin and exendin-4 share highly significant structural similarity in their extracellularly-oriented amino-termini. We propose that molecular mimicry has generated conserved structural motifs in secretagogic toxins and their receptors, thereby explaining the evolution of defense or predatory strategies that are shared in common amongst distantly related species including spiders, lizards, and snakes. Evidently, the toxic effects of alpha latrotoxin and exendin-4 are explained by their ability to interact with GTP binding protein-coupled receptors that normally mediate the actions of endogenous hormones or neuropeptides. PMID- 9972295 TI - Lipoprotein lipase activity and mRNA levels in bovine tissues. AB - Lipoprotein lipase (LPL) in cattle has been extensively studied in adipose tissue, milk and mammary gland, but only to a limited extent in muscles. Therefore, we have adapted our in vitro LPL assay method for the measurement of LPL activity and describe, for the first time, sensitive procedures to quantify LPL activity and mRNA levels in bovine muscles. In vitro activation of bovine LPL activity is approximately 5-fold greater with rat than with bovine sera for heart and muscles, but not for adipose tissues. Values of LPL activity are in the upper range of those previously reported for rat or bovine tissues. With rat serum as activator, LPL activity in the heart of seven calves (662-832 mU g-1) is at least 3-fold lower than in the rat heart (2150-2950 mU g-1, P < 0.05). LPL activity is higher in bovine heart and oxidative muscles (412-972 mU g-1), except the diaphragm, than in mixed or glycolytic muscles (33-154 mU g-1, P < 0.05). The levels of LPL transcripts are positively related to LPL activity in bovine tissues, including muscles and adipose tissues. PMID- 9972296 TI - Cloning and sequence analysis of the aminopeptidase N isozyme (APN2) from Bombyx mori midgut. AB - An aminopeptidase N (APN) isozyme having the molecular weight of 90 kDa, was released by phosphatidylinositol-specific phospholipase C (PI-PLC) and purified homogeneously, from the brush border membrane of Bombyx mori. From the result of cDNA cloning, the primary structure of 90 kDa APN proved to consist of 948 amino acid residues, containing a typical metalloprotease-specific zinc-binding motif in the deduced sequence. Moreover, the primary sequence contained two hydrophobic segments on N- and C-termini. The N-terminal one showed characteristics of leader peptide for secretion and the C-terminal one contained a possible glycosylphosphatidylinositol (GPI) anchoring site, suggesting that the APN encoded by the cDNA is not only a zinc-binding enzyme, but also a GPI-anchored protein. The primary sequence is significantly homologous with those of insect and mammalian APNs, and contains four conserved segments around the zinc-binding motif, two potential N-glycosylation sites and four conserved Cys residues. The deduced primary sequence had 30.7% identity with that of B. mori 110 kDa APN, and did not contain the N-terminal and internal amino acid sequences of B. mori 100 kDa APN, revealing B. mori 90 kDa APN to be the third isozyme on the midgut brush border membrane. On the other hand, the primary sequence of 90 kDa APN showed high homology with Manduca sexta APN2 (65.1% identity) and Plutella xylostella APN2 (63.8% identity). It appears that the B. mori 90 kDa APN should be classified in the insect apn2 cluster and differentiated from insect apn1 and mammalian apn clusters by phylogenetic analysis. These results suggest that 90 kDa APN isozyme encoded by the cDNA is a product of B. mori apn2 gene. PMID- 9972297 TI - Comparative effects of short- and long-term feeding of safflower oil and perilla oil on lipid metabolism in rats. AB - Diets high in linoleic acid (20% safflower oil contained 77.3% linoleic acid, SO diet) and alpha-linolenic acid (20% perilla oil contained 58.4% alpha-linolenic acid, PO-diet) were fed to rats for 3, 7, 20, and 50 days, and effects of the diets on lipid metabolism were compared. Levels of serum total cholesterol and phospholipids in the rats fed the PO-diet were markedly lower than those fed the SO-diet after the seventh day. In serum and hepatic phosphatidylcholine and phosphatidylethanolamine, the proportion of n-3 fatty acids showed a greater increase in the PO group than in the SO group in the respective feeding-term. At the third and seventh days after the commencement of feeding the experimental diets, expressions of hepatic 3-hydroxy-3-methylglutaryl coenzyme A reductase mRNA were significantly higher in the SO group than those in the PO group, although the difference was not observed in the longer term. There were no significant differences in the LDL receptor mRNA levels between the two groups through the experimental term, except 3-days feeding. These results indicate that alpha-linolenic acid has a more potent serum cholesterol-lowering ability than linoleic acid both in short and long feeding-terms. PMID- 9972298 TI - cDNA cloning and expression analysis of flounder p53 tumour suppressor gene. AB - The screening of a flounder cDNA library with a rainbow trout p53 probe allowed the isolation of a 2.8-kb fragment homologous to human (50%) and rainbow trout (57%) p53 coding sequences. The fragment contains a single open reading frame coding for a 366-amino acid protein. The predicted amino acid sequence is relatively divergent from other p53 proteins but it displays the main p53 features: five highly conserved domains, an acidic N-terminus, a hydrophilic and charged C-terminus, a penultimate serine residue and a putative nuclear localization signal. Furthermore, conservation of critical amino acids and comparable distribution of charge and hydrophobicity suggest that flounder p53 properties could be similar to those in mammals. Northern blot analysis revealed a single transcript of about 3 kb in the flounder ovary tissues. In fact, RT-PCR showed an ubiquitous but very low expression of p53 gene in all flounder tissues. PMID- 9972299 TI - Purification and characterization of two cysteine proteinase inhibitors from the skin of Atlantic salmon (Salmo salar L.). AB - Two cysteine proteinase inhibitors, designated Tromsin I and II, were purified from the skin of Atlantic salmon, using three steps of chromatography, including affinity, anion exchange and gelfiltration. The two cysteine proteinase inhibitors were both of the high molecular weight type, with apparent MW 49 and 76 kDa. The isoelectric points (pI) of Tromsin I and II were estimated to be 4.5 and 5.2, respectively. The inhibitors were both stained by the PAS reaction for carbohydrates, and showed a remarkable heat stability. Western blotting revealed that the inhibitors also could be found in significant amounts in serum. Tromsin I and II share many common features with members of the family 3 cystatins, i.e. mammalian kininogen, such as molecular weight, papain inhibition and tissue distribution. Based on N-terminal sequence from Tromsin II however, no homology with known cysteine proteinase inhibitors can be found. This does not exclude that the inhibitors belong to the family 3 cystatins, because the N-terminal amino acid sequences of known cysteine proteinase inhibitors show very low homology. PMID- 9972300 TI - Comparative study of the cytoplasmic domain of band 3 from human and rabbit erythrocyte membranes. AB - The cytoplasmic domain of band 3 (cdb3) is thought to play an important role in human erythrocyte aging. In order to investigate the role of cdb3 during rabbit erythrocyte aging, we compared rabbit cdb3 with the corresponding protein from human erythrocyte membranes. We describe a purification procedure for rabbit cdb3 comparing rabbit and human cdb3 on sodium dodecyl sulphate-polyacrylamide electrophoresis, we found fragments of different molecular weights, implying different chymotryptic cuts in the two species. Anti-human antibodies did not bind to the rabbit cdb3; we also noticed structural differences in the protein between the two species, which may also play a role in the aging processes. Rabbit erythrocyte membranes have a higher capacity of binding hemichromes, due to the higher content of band 3. While in rabbit erythrocyte membranes only one binding site for hemichromes (corresponding to cdb3) was found, we confirmed the existence of two binding sites in human membranes. The second binding site probably corresponds to glycophorin, a protein not present in rabbit membranes. PMID- 9972302 TI - Cloning, sequencing and characterization of the tilapia insulin gene. AB - Using degenerate primers based on insulin sequences from other organisms, we report the cloning of the complete tilapia (Oreochromis niloticus) insulin gene. Using nested primers and a cassette ligation strategy we have also cloned 932 base pairs (bp) of 5' flanking and 1152 bp of 3' flanking sequence. The tilapia insulin gene has the similar three exon (one untranslated), two intron distribution found in all insulin genes sequenced to date. However, intron 1 is unique in having a smaller size (73 bp) than found in other organisms. 5' RNA extension revealed the presence of two potential transcriptional start sites. A perfect TATA box is located at -30 bp from the first transcriptional start site. Interestingly, the 5' upstream region contains a microsatellite close to the same position of a unique minisatellite found only in humans and primates. The upstream region also contains several potential control elements to regulate insulin expression that are found in mammalian insulin genes. PMID- 9972303 TI - Shrimp plasma HDL and beta-glucan binding protein (BGBP): comparison of biochemical characteristics. AB - A high density lipoprotein (HDL) and beta-glucan binding protein (BGBP) have been found in the hemolymph of marine shrimp. These proteins are involved in the transport of lipid and the recognition of foreign matter, respectively. Similarities in the color of the proteins and the molecular mass were noted. For a detailed comparison, HDL and BGBP were purified from two shrimp species, Penaeus vannamei and Penaeus californiensis, and their biochemical characteristics determined. Both proteins from each of the shrimp species are monomeric with approximately the same molecular mass in sodium dodecyl sulfate polyacrylamide gel electrophoresis (approximately 100-112 kDa) and contain carbohydrate and lipid. The amino acid composition is similar and there is a high degree of similarity in the N-terminus. Furthermore, they are recognized by antibodies prepared independently. These results reveal that BGBP and HDL in shrimp hemolymph are the same protein, suggesting that there is a close relationship between the ability to respond to foreign matter and the diet as a provider of essential nutrients. PMID- 9972304 TI - Comparison of four monoclonal antibodies reacting with gastric gland mucous cell derived mucins of rat and frog. AB - Features of four monoclonal antibodies (MAbs), PGM36, PGM37, PGM38 and HIK1083, reacting with the mucin derived from rat gastric gland mucous cells were compared. By applying enzyme linked immunosorbent assay, all of these MAbs reacted not only with the mucins purified from both rat and frog stomach, but also with the oligosaccharides obtained from the antigenic mucins by alkaline borohydride treatment. These MAbs could be characterized as distinct MAbs due to the immunohistochemical observation of rat cecal mucosa and the reactivity to paranitrophenyl derivatives of monosaccharides. These MAbs might be useful tools to compare the gastric gland-type mucins in different species of vertebrates and to investigate the heterogeneity of the carbohydrate structure of the mucin molecules of various origins. PMID- 9972305 TI - Distribution of cathepsin E in the larval and adult organs of the bullfrog with special reference to the mature form in the larval fore-gut. AB - The distibution of cathepsin E in several organs of the bullfrog, Rana catesbeiana, was analyzed at pre- and post-metamorphic stages by the acid proteinase assay, by visualization of enzyme activity on polyacrlamide fore-gut gels after electrophoresis and by immunoblotting with anti-cathepsin E serum. Cathepsin E was mainly distributed in the foregut at the larval stage and in the stomach, duodenum, large intestine and gall bladder at the post-metamorphic stage. In the larval fore-gut, a higher amount of the mature form of cathepsin E was observed in addition to the proform, but in other organs, including the stomach at the post-metamorphic stage, the mature form was barely detected. Developmental changes in the amount of cathepsin E were found in the digestive tract and the gall bladder by quantitative immunoblotting analysis. Finally, the larval fore-gut was stained immunohistochemically with anti-cathepsin E serum and the surface epithelium gave a strong immunoreactive signal. PMID- 9972306 TI - "cDNA cloning and predicted primary structure of scalllop sarcoplasmic reticulum Ca(2+)-ATPase" [Comp Biochem Physiol 119B(1998)777-785]. PMID- 9972307 TI - Ontogeny of humoral immunity in northern elephant seal (Mirounga angustirostris) neonates. AB - Northern elephant seal (NES) serum concentrations of total immunoglobulin (Ig) G, an IgG sub-class, and an IgM-like protein were determined by capture immunoassay using three monoclonal antibodies with specificities for Ig of members of the Phocidae pinniped family. These assays were calibrated for use with NES sera using affinity column purified Ig. Concentrations of these Ig populations were estimated in adult female sera sampled at two time points during the lactation period, as well as sera from their pups collected during the first 5 weeks after birth. In pups, concentrations of the IgM-like protein was found to increase rapidly post-partum. In some individuals, values reached mean concentrations within 10-14 days. In addition, rapid increases in pup total IgG and IgG sub class concentrations were also observed. Collectively, these findings suggest that the majority of post-partum increases in serum Ig can be accounted for by de novo synthesis. PMID- 9972308 TI - Characterization of fish acid proteases by substrate-gel electrophoresis. AB - Several analytical techniques based upon the use of substrate-polyacrylamide gel electrophoresis were evaluated to achieve characterization of aspartate proteases in fish stomach. Since aspartate proteases of fish are more stable at high pH than mammalian pepsins, the most accurate technique for activity assessment is electrophoresis at neutral pH and revealing of such activity at low pH with hemoglobin as substrate. The technique is suitable for characterization of proteases and in comparative assessment of acid protease activity in different sparids. PMID- 9972309 TI - Partial purification and kinetic properties of three different D-glucosamine 6 P:N-acetyltransferase forms from human placenta. AB - Three distinct forms of D-glucosamine 6-D (Gm 6-P):N-acetyltransferases (EC 2.3.1.4) were partially purified from human placental homogenates by carboxy methyl-Sephadex chromatography. Purification of forms I and II were 13.5-fold, while that of form III was 114-fold. All three forms had a pH optimum value of 9.7 in glycine-NaOH buffer. Enzymes II and III had a K(m) value for Gm 6-P of 3.0 mM, which was less than half of that observed for form I (7.1 mM). The corresponding K(m) values for acetyl CoA were 0.157 (form I), 0.187 (form II) and 0.280 mM (form III), respectively. Activities of all three forms were inhibited at high concentrations of either substrate. These enzymes were inhibited from 82 to 92% by 2.5 mM p-chloromercuribenzoate. The inhibition was largely reversible by inclusion of 2.5 mM dithiothreitol in the incubation mixtures. There was no requirement for divalent cations, as demonstrated by lack of inhibition of enzyme activity by ethylene diamine tetraacetate. The results are discussed in terms of differences among the enzyme properties of human placental, rodent and porcine liver forms. PMID- 9972310 TI - Selective excretion of yolk-derived tocotrienols into the bile of the chick embryo. AB - The aim of this study was to investigate the possibility of biodiscrimination between different forms of vitamin E during the development of the chick embryo. The vitamin E present in the initial yolk consisted of alpha-tocopherol (90%), (beta + gamma)-tocopherol (8%), alpha-tocotrienol (0.3%) and (beta + gamma) tocotrienol (1.3%). In marked contrast, the vitamin E recovered from the bile of the day-16 embryo contained much higher proportions of alpha-tocotrienol (10%) and especially of (beta + gamma)-tocotrienol (42%). By the time of hatching, 56% of the vitamin E present in the bile was in the form of (beta + gamma) tocotrienol. The residual yolk of the newly-hatched chick contained far greater proportions of alpha-tocotrienol (2.6%) and (beta + gamma)-tocotrienol (10%) than were present in the initial yolk. The results suggest that the liver of the embryo may selectively excrete tocotrienols as components of bile, whilst retaining the tocopherols within the hepatocytes. The increased proportions of tocotrienols in the residual yolk may result from the recycling of bile from the gall bladder to the yolk. The liver of the day-old chick contained alpha tocopherol as the main form of vitamin E (90%) with only a small proportion (0.2%) of (beta + gamma)-tocotrienol. The alpha-tocopherol form was also the main vitamin E component in the brain (85%), heart (79%), lung (82%) and adipose tissue (91%) of the day-old chick. The present study suggests the occurrence of a high degree of biodiscrimination between tocopherols and tocotrienols during the development of the chick embryo. PMID- 9972311 TI - Identification and structural characterization of a novel member of the vitamin D binding protein family. AB - The apparent high degree of homology of a blood protein with a unique dual binding affinity for two distinct hormones, thyroxin (T4) and vitamin D, isolated from a turtle, Trachemys scripta (Family Emydidae) and mammalian vitamin D binding protein (DBP) prompted further interspecific comparison to better understand the structure of functional binding sites. Using polymerase-chain reaction (PCR) with primers derived from the putative nucleotide sequences encoding peptides from the degradation of the T. scripta protein, we cloned the cDNA. The mature turtle protein contains 466 amino acids, about eight residues more than in mammalian DBP. The nucleotide sequence of the coding region showed 63% nucleotide and 73% amino acid homology (approximately 53% identity) to mammalian DBP (human, rat, mouse, and rabbit). However, there was no significant homology to mammalian T4-binding globulin (TBG) or transthyretin (TTR). Comparisons with mammals help define further the requirements for the vitamin D and actin binding sites. Northern blots of RNA isolated from turtle tissue probed with the 5' portion of cDNA established expression of the transcript in liver, kidney, and brain (in order of abundance), in contrast to mammal sequences in which expression of DBP is largely confined to the liver. PMID- 9972312 TI - Modulation of peroxisomal and microsomal fatty acid oxidation by acetone. A comparative study between liver and kidney. AB - The effect of acetone consumption on some microsomal and peroxisomal activities was studied in rat kidney and these results were compared with data from former investigations in liver. Acetone increased the microsomal lauric acid hydroxylation, the aminopyrine N-demethylation catalyzed by cytochrome P450 and the microsomal UDP-glucuronyltransferase activity. Also, acetone increased the peroxisomal beta-oxidation of palmitoyl CoA and catalase activities in kidney. These studies suggest that acetone is a common inducer of the microsomal and peroxisomal fatty acid oxidation, as previously shown in both starved and ethanol treated rats. Our results support the hypothesis that microsomal fatty acid omega hydroxylation results in the generation of substrates being supplied for peroxisomal beta-oxidation. We propose that the final purpose of these linked fatty acid oxidations could be the catabolism of fatty acids or the generation of a substrate for the synthesis of glucose from fatty acids. This pathway would be triggered by acetone treatment in a similar way in liver and kidney. PMID- 9972313 TI - Reduced alkaline phosphatase activity in diabetic rat bone: a re-evaluation. AB - We found previously that human bone alkaline phosphatase (AP) was glycated by aseptic incubation with glucose, and partially broken down by reactive oxygen species. In this study, we examined whether selective in vivo glycation of AP molecules occurred in bone tissue, using experimental diabetic rats induced by streptozotocin and spontaneously diabetic rats. Additionally, the effects of hyperlipidemia on bone AP activity were examined. Serum AP activity was significantly elevated after incipient onset of diabetes, and the increased activity originated from the intestinal isozyme. High levels of intestinal AP activity were also observed in rats with hyperlipidemia induced by feeding high fat or high-fructose chow, but the AP activity in bone tissues was maintained at a constant level. AP activity in bone was reduced after the onset of diabetes. The resulting bone AP molecule bound to an aminophenylboronic acid column, which had affinity for glycated proteins, and contained smaller molecular sizes than the native bone AP. These results suggest that elevated levels of serum AP activity originated from the intestinal isozyme accompanied with hyperlipidemia induced by diabetes. In contrast, the reduced serum levels of AP activity in diabetic rats might be dependent on inactivation of bone AP, which was glycated, followed by partial breakdown of bone AP molecules, possibly due to reactive oxygen species. PMID- 9972314 TI - An enzyme-linked immunosorbent assay (ELISA) for measuring vitellogenin in English sole (Pleuronectes vetulus): development, validation and cross-reactivity with other pleuronectids. AB - Vitellogenin (Vtg) is a yolk protein produced in the liver of oviparous animals in response to estrogen. Vitellogenesis is normally observed only in sexually mature females, but it can be induced in male and juvenile animals by exposure to exogenous estradiol (E2) or substances that mimic estrogens. The abnormal production of Vtg by males can, therefore, be used as a biological indicator for exposure to xenoestrogens. In this study, an enzyme-linked immunosorbent assay (ELISA) for measuring Vtg in English sole (Pleuronectes vetulus) was developed and validated. Plasmatic Vtg was purified from E2-injected male English sole using DEAE ion-exchange and Sepharose size-exclusion chromatography, and polyclonal antibodies against the purified Vtg protein were generated in rabbits. In this assay, a competition for the Vtg antibody was established between Vtg coated onto microtiter plate wells and free Vtg. Detection of adsorbed antigen antibody complexes was achieved using a horseradish peroxidase conjugated anti rabbit secondary antibody whose enzyme activity was revealed with 3,3',5,5' tetramethyl benzidine (TMB) substrate. Assay conditions provided a detectable Vtg range of 10-450 ng ml-1 (85-20% of binding) of diluted sample. Plasma dilution curves from vitellogenic female and E2-treated male English sole showed parallelism with the standard dilution curve. We are presently conducting field and laboratory studies to investigate estrogenic and anti-estrogenic activity resulting from exposure to contaminants. PMID- 9972315 TI - Isolation and characterization of proteoglycans from growing antlers of wapiti (Cervus elaphus). AB - Proteoglycans were extracted with 4 M guanidine-HCl from the zone of maturing chondrocytes, the site of endochondral ossification of growing antlers of wapiti (Cervus elaphus). Proteoglycans were isolated by DEAE-Sephacel chromatography and separated by Sepharose CL-4B chromatography into three fractions. Fraction I contained a high molecular mass (> 1000 kDa) chondroitin sulfate proteoglycan capable of interacting with hyaluronic acid. Its amino acid composition resembled that of the cartilage proteoglycan, aggrecan. Fraction II contained proteoglycans with intermediate molecular weight which were recognized by monoclonal antibodies specific to chondroitin sulfate and keratan sulfate. Fraction III contained a low molecular mass (< 160 kDa) proteoglycan, decorin, with a glucuronate-rich glycosaminoglycan chain. PMID- 9972316 TI - Detection of a P-glycoprotein related pump in Chironomus larvae and its inhibition by verapamil and cyclosporin A. AB - A membrane associated ATP-dependent efflux pump, similar in function to mammalian P-glycoprotein, was detected in anal papillae of Chironomus riparius larvae. Immunohistochemical analysis of larval tissues, using monoclonal antibodies against P-glycoprotein, was supplemented by functional in vivo and in vitro assays which confirmed the existence of a mechanism for transporting xenobiotic substances. The in vitro ATPase activity of homogenate fractions increased in the presence of typical P-glycoprotein substrates (vinblastine, actinomycin D or ivermectin). This increase was unaffected by inhibitors of other membrane ATPases (sodium azide, EGTA, ouabain), but sensitive to vanadate, cyclosporin A and verapamil which inhibit mammalian P-glycoprotein mediated ATP-consumption. Sublethal concentrations of specific P-glycoprotein-inhibitors such as verapamil or cyclosporin A synergistically enhanced the mortality of C. riparius towards ivermectin. Although cyclosporin A originates from entomopathogenic fungi, its mode of action in insects and its function during infection are not understood. Our results lend some credit to the hypothesis that this compound is possibly released to promote poisoning of the infected host by xenobiotics which are normally removed by a P-glycoprotein related pump. The putative role of insect P glycoprotein homologues in the context of multiple resistance towards insecticides in discussed. PMID- 9972318 TI - In vivo prevention of cyclophosphamide-induced Ca2+ dependent damage of rat heart and liver mitochondria by cyclosporin A. AB - The use of Cyclophosphamide, an anti-cancer and immunosuppressant drug, is accompanied by a number of side effects. Rats injected with a single dose of cyclophosphamide (200 mg kg-1 body weight) showed an increase in the levels of serum glutamate-oxaloacetate transaminase, serum glutamate-pyruvate transaminase, glucose-6-phosphate dehydrogenase and creatine phosphokinase isoenzyme by 53, 24, 55 and 135%, respectively. Also the ability of heart or liver mitochondria to retain accumulated Ca2+ and tetraphenylphosphonium ion was sharply affected in treated rats. Rats injected with the same dose of cyclophosphamide plus cyclosporin A (500 micrograms kg-1 body weight) showed reduction in the levels of those enzymes by about 44, 21, 43 and 57%, respectively compared to cyclophosphamide-treated rats. Cyclosporin A treatment also restored mitochondrial ability to retain accumulated Ca2+ and tetraphenyl phosphonium ions nearly to the level of untreated rats. We suggest that cyclophosphamide induced cardio and hepatotoxicity by increasing heart and liver inner mitochondrial membrane permeability to Ca2+. The protective effect of cyclosporin A against cyclophosphamide-induced damage also support this suggestion. PMID- 9972319 TI - Geographic variations in the composition of myotoxins from Bothrops neuwiedi snake venoms: biochemical characterization and biological activity. AB - (1) Venom pools from Bothrops neuwiedi (Bn) and from two subspecies, namely Bothrops neuwiedi pauloensis (Bnp) and Bothrops neuwiedi urutu (Bnu), collected in the States of Sao Paulo (SP) and Minas Gerais (MG), Brazil, were electrophoretically examined. Basic toxins with different isoelectric points were identified in the venom collected in Sao Paulo (BnSP). These toxins were absent in the corresponding pools from Minas Gerais (BnMG, BnpMG and BnuMG). (2) BnSP, but not BnMG, BnpMG or BnuMG, showed two myotoxins (pI approximately equal to 8.6 and 8.8, respectively) which were isolated by ion-exchange chromatography on CM Sepharose. (3) From BnMG, three myotoxic isoforms (pI approximately equal to 8.2 and M(r) = 13,600) were isolated by chromatography on CM-Sepharose followed by reversed-phase high-performance liquid chromatography. (4) The chemical and biological characterization of these toxins showed a high similarity with the Lys 49 myotoxins from other bothropic venoms. (5) Doses up to 5 LD50 (i.p.) of p bromophenacyl bromide alkylated BnSP-7 caused a total loss of lethality in 18-22 g mice, thus indicating that the LD50 was increased by greater than 5-fold. At this dose myotoxicity was also not detectable, but the edematogenic activity on the rat paw apparently did not change. PMID- 9972320 TI - Serum and antral gastrin levels in fed and fasted rats: relation to aging. AB - The effect of short fasting for up to 24 h on serum and antral gastrin concentrations and G cell ultrastructure has been examined in the young rat compared with the middle-aged rat. The serum gastrin levels at 24-h fasting were markedly reduced in both young and middle-aged rats. There was also a significant decrease in antral gastrin concentrations after 24 h of fasting in the middle aged rats. By contrast, the antral gastrin concentrations in the young rats increased progressively and significantly with fasting for up to 24 h. These responses were associated with a significant increase in the content of secretory granules of G cell, which was at its greatest by 24 h. The antral gastrin level in the 48-h fasting rats was markedly reduced to a level below that for the prestarvation group. By 48 h of starvation, the amount of secretory granules in G cell was significantly reduced (P < 0.05) compared with the 24-h fasting group. These results indicate that the effects of fasting on the antral gastrin levels in young rats differ from those of the middle-aged and that starvation for up to 24 h caused a significant increase in the antral gastrin content in the young rats' stomach. PMID- 9972321 TI - Histamine receptors in the skin melanophores of Indian bullfrog Rana tigerina. AB - Histamine and 2-methyl histamine caused dose-dependent aggregation of the integumental melanophores of Rana tigerina both in vitro and in vivo. The aggregating effects were antagonised by mepyramine and metiamide, specific H1 and H2 receptor blockers, respectively. Compound 48/80 and EDTA augmented the melanin aggregating effects of exogenously applied histamine and 2-methyl histamine in in vivo experiments. 4-Methyl histamine, a specific H2 receptor agonist, dispersed the frog melanophores in in vitro studies, the dispersing effects were blocked by metiamide. PMID- 9972322 TI - Effects of short-term dehydration on plasma osmolality, levels of arginine vasotocin and its hypothalamic gene expression in the laying hen. AB - The neurohypophysial hormone, arginine vasotocin (AVT), plays an important role in the osmoregulation of birds. After a prolonged period of water deprivation, plasma osmolality and plasma concentration of AVT are elevated. In this study, the effects of short term dehydration were examined in laying hens by measuring plasma osmolality, plasma levels of potassium, sodium and AVT and hypothalamic concentrations of mRNA encoding AVT during 8 h of water deprivation. Plasma osmolality increased significantly after at 6 h of water deprivation. Plasma sodium levels, however, did not change. Plasma potassium concentrations gradually decreased during dehydration. Plasma AVT levels and hypothalamic AVT mRNA levels increased significantly after 8 h. The results of this study demonstrate that depriving chickens of water results first in an increase in plasma osmolality followed by increases in AVT levels in plasma and AVT mRNA levels in the hypothalamus. The data indicate that the synthesis of AVT in the magnocellular neurons in the hypothalamus is activated soon after the animals are deprived of water. This indicates that both de novo synthesized AVT as well as AVT stored in the neurohypophysis are available to meet the increasing demands for the hormone during osmotic stress. PMID- 9972323 TI - Serum prolactin and dehydroepiandrosterone concentrations during the summer and winter hair growth cycles of mink (Mustela vison). AB - We investigated the relationship between serum concentrations of prolactin (PRL) and dehydroepiandrosterone (DHEA) during initiation and development of summer and winter hair growth (anagen) cycles in mink. In the spring, haloperidol (HAL) increased PRL concentrations and induced summer anagen earlier than controls, whereas melatonin (MEL) inhibited PRL secretion and completely blocked summer anagen. In the fall, HAL increased PRL concentrations, inducing anagen at an earlier time than controls, although the resulting fur was abnormal being almost devoid of underhair fibers. Exogenous MEL during the fall reduced PRL concentrations, initiating winter anagen 4 weeks earlier than controls. Adrenalectomy (ADX) induced earlier onset of summer and winter anagen and neutralized the inhibitory effects of HAL in the fall and MEL in the spring. No change in serum DHEA concentrations was observed during the onset of summer or winter anagen in any group although MEL increased DHEA levels from 27 March through 5 June relative to HAL-treated mink. We conclude that changes in serum levels of DHEA and PRL are not requisite to onset of summer or winter anagen in mink. It is possible that metabolites of DHEA and/or PRL may still affect other aspects of the hair growth cycle. PMID- 9972324 TI - Submaximal exercise in the cold: does cooling potentiate the development of muscle injuries in the rat? AB - To test the effect of low ambient temperature on muscular strain and possible development of muscle injuries, male Sprague-Dawley rats (n = 35) were exercised at a speed of 15 m min-1 on a treadmill at a 6 degrees inclination for 1.5 h in a warm (22 degrees C) or a cold (-10 degrees C) environment. Blood and tissue samples were collected 0 and 48 h postexercise. Blood glucose, lactate, pyruvate, cortisol, epinephrine (E) and norepinephrine (NE) were determined to investigate the effect on energy metabolism. To estimate the degree of physical strain, possible muscle injury and regenerative processes of muscles in response to exercise in the cold, serum creatine kinase (CK), lactate dehydrogenase (LDH), muscle beta-glucuronidase and prolyl-4-hydroxylase (PH) activities were measured. In addition, histology of the hindlimb muscles m. soleus and m. tibialis anterior was examined. In general, the circulating level of metabolic substrates during exercise were unaffected by the exercise and independent of ambient temperature. Plasma cortisol increased significantly during exercise (P < 0.01), but was unaffected by the thermal strain. Of the myocellular enzymes, serum CK increased by 100% (P < 0.01) and LDH by 93% (P < 0.05) during exercise in the cold compared with exercise in warm, indicating a higher physical strain. However, exercise in the cold did not result in muscle injuries as judged by the unaltered muscular beta-glucuronidase, PH levels and muscle morphology. It is concluded that the exercise type and intensity used caused stress that was independent of the ambient temperature. In addition, the rats were able to maintain unaltered circulating levels of energy substrates also in the cold. Finally, exercise in the cold increased muscular strain but did not result in muscle injuries. PMID- 9972325 TI - Effect of intermittent feeding on the development of disaccharidase activities in artificially reared rat pups. AB - We investigated the effect of an intermittent feeding schedule on the development of disaccharidase activities in the small intestine of artificially reared (AR) rat pups. Rat pups were fitted with an intragastric cannula at 5 days of age. A milk formula similar to the composition of rat milk was supplied by intermittent gastric infusion over the following 15-19 days. The body weight gain and plasma corticosterone levels of the AR pups matched those of pups reared naturally by dams (MR pups). At 10, 15 and 19 days of age, the small intestine from the ligament to Treitz to the ileocecal junction was divided into three segments of equal length and enzyme activities were measured in each. At the age of 10 and 15 days, sucrase and isomaltase activities were undetectable in AR pups fed according to a controlled schedule from the early postnatal period. These activities were first detected in the middle segment of the small intestine at 9 days of age in both AR and MR pups. Sucrase and isomaltase activities at the age of 19 days were diurnal in AR pups, but arrhythmic in MR pups. We conclude that artificial rearing via the intermittent gastric infusion of a milk formula containing only lactose as the carbohydrate source did not prematurely increase intestinal sucrase and isomaltase activities. Diurnal changes started from the beginning of development of these enzyme activities in AR pups. PMID- 9972326 TI - Glaucoma, apoptosis, death, and life. PMID- 9972327 TI - Molecular basis of open-angle glaucoma in Italy. AB - Glaucoma is a group of ocular diseases characterized by an optic neuropathy in which degeneration of retinal ganglion cells leads to a characteristic excavation of the optic nerve head. Primary open-angle glaucoma (POAG) can be subdivided into two groups according to age of onset:- 1. the more common middle- to late age onset, chronic open-angle glaucoma (COAG) diagnosed after the age of 40 years; 2. the rarer juvenile open-angle glaucoma (JOAG), which is diagnosed between the age of 3 years and early adulthood. Recently, the gene coding for the trabecular meshwork-induced glucocorticoid response protein (TIGR), located in chromosome 1 (1q23-25), was found mutated in patients affected by POAG. In this work we describe the clinical and molecular genetic features of several Italian families affected by autosomal dominant POAG, collected in various regions of Italy. PMID- 9972328 TI - The role of class I and class II HLA antigens in primary open angle glaucoma (POAG). AB - Several clinical and epidemiological studies have shown the role of genetic factors in the pathogenesis of primary open angle glaucoma (POAG). In this study, 30 patients affected by this disease were tissue-typed for HLA Class I and Class II antigens. The results pointed up an increased incidence of some antigens and, particularly, a statistically significant association with DQ1 and DR11 alleles. PMID- 9972329 TI - Induced acute ocular hypertension: mode of retinal cell degeneration. AB - The effects of experimental hypertension on retinal cells were studied. Evaluation was made of IOP levels and degree of cell damage by cytochemical and DNA analysis, and degeneration modes: necrosis and apoptosis. PMID- 9972330 TI - The Draeger autotonometer: its advantages and limits. PMID- 9972331 TI - Frequency doubling perimetry in glaucoma early diagnosis. AB - Frequency-doubling perimetry (FDP) is a new, out-of-the-ordinary, visual field testing method. Its sensitivity and reliability was tested in 16 patients (32 eyes) with ocular hypertension and 21 patients (37 eyes) with early chronic glaucoma. Significant defects were found in almost 10% of hypertensive eyes and in 67.7% of glaucomatous eyes. FDP is an effective and sensitive technique for glaucoma functional loss assessment. PMID- 9972332 TI - Blue-yellow perimetry in patients with ocular hypertone. AB - The authors report the data of the blue-yellow (B-Y) perimetry compared with the Standard perimetry in normal subjects with endocular hypertension or with initial glaucoma. With the aim of evaluating the relationship with chromatic sense deficits, precociously found in glaucoma, the F-M 100 Hue test and Lanthony D 15 Desature test were done. Checks were made of refraction, visual acuity, pupil diameter and assumption of medications. Sensitivity reduction in eyes with initial glaucoma is highly significant with the B-Y perimetry. Pupil diameter reduction is quite uninfluential while the chromatic sense shows some quantitative and qualitative deficits. PMID- 9972333 TI - Pattern electroretinogram and optic nerve topography in ocular hypertension. AB - It is known that changes in pattern electroretinogram (PERG) and optic disk morphology may both precede the onset of visual field damage in glaucomatous disease. However, the relationship between PERG and optic disk morphometry in ocular hypertension (OHT) has not yet been evaluated in detail. This study of PERG amplitude in a group of OHT patients indicates its significant correlation with various optic disk morphometric parameters, in particular, those of optic disk sectors considered at risk for early glaucomatous damage. Analysis of individual data points to the possibility that, while functional abnormalities may often precede optic disk morphologic changes, in a much lower number of cases it seems to be the other way around. PMID- 9972334 TI - The nerve fibre layer in ocular hypertension. Preliminary results. AB - A group of healthy subjects (IOP < 22 mmHg) and a simple ocular hypertension group (IOP > or = 22 mmHg) were examined with a view to checking if there were any differences between their nerve fibre layers. Results indicate thinner fibres in the ocular hypertensives significantly correlative with pressure increase. Among the two groups, some corresponding fibre thicknesses were found. PMID- 9972335 TI - Ultrasound biomicroscopy as decisive examination in resolving special glaucoma cases. PMID- 9972336 TI - Ultrabiomicroscopic study of the effects of brimonidine, apraclonidine, latanoprost and ibopamine on the chamber angle and ciliary body. AB - The authors used the Zeiss Humphrey (Mod840, 50 MHz) ultrabiomicroscope to evaluate the changes that Brimonidine, Apraclonidine, Latanoprost and Ibopamine cause in the anterior chamber and on the ciliary body of healthy subjects. The eyes of 60 volunteers, separated into 4 groups according to drug instilled, were studied and the parameters analyzed were: anterior chamber depth (ACD), pupillary diameter (PD), angle opening at 500 microns from the scleral spur (AOD500), trabecular iris angle (TIA) and iris thicknesses (ID1 and ID3). The study showed the miotic effect of Brimonidine (S) that was accompanied by an angle opening (S). Apraclonidine and Latanoprost caused no statistically significant changes in the angle or in the ciliary body. Ibopamine caused mydriasis (S). The UBM, therefore, showed itself to be useful also in the study of the mechanism of action of drugs on the angular structures and on the ciliary body. PMID- 9972337 TI - Pupillographic, tonographic and refractive parameter changes after topical instillation of Brimonidine tartrate 0.2% in healthy subjects. PMID- 9972338 TI - Effects of brimonidine 0.2% on blue-yellow perimetry of glaucomatous patients. AB - A cross-over double-blind study was performed to evaluate the effect of acute administration of brimonidine on the blue-yellow perimetry. Thirty patients with primary open-angle glaucoma were admitted. After brimonidine administration, IOP and pupil diameter showed a significant reduction (p < 0.01) without modification in systolic and diastolic blood pressure. Blue-on-yellow perimetry showed a significant reduction in CPSD from 3.81 +/- 1.60 to 2.71 +/- 1.92 (p < 0.05). This result suggests that brimonidine improves ocular perfusion via a reduction of IOP. PMID- 9972339 TI - Clinical use of a topical carbonic anhydrase inhibitor in patients affected by chronic simple glaucoma. AB - The aim of this study is to evaluate the ocular hypotensive efficacy of a topical carbonic anhydrase inhibitor (dorzolamide) in primary open-angle glaucoma patients, administered alone or in association with beta-blockers or with beta blockers and miotics, in a one-year follow-up. PMID- 9972340 TI - Sympathetic use of latanoprost 0.005% in 30 eyes. AB - In this study, the authors report their experience with latanoprost after a year's treatment of patients with various forms of glaucoma at various stages of progression. The new drug was associated also with different beta-blockers. The case file reported includes 30 eyes of 18 patients treated with latanoprost once a day in the evening. Follow-up varied from 6 months to 1 year. Except for 2 patients (3 eyes) receiving only latanoprost therapy, all the others received latanoprost in association with their on-going therapy. Results are equivalent to those described in the literature. The authors also consider the results in two groups; chronic simple glaucoma and other forms of glaucoma. From their own experience and from what is reported in the literature, the authors conclude by stressing the pressure reducing efficacy of this drug. PMID- 9972341 TI - Latanoprost 0.005% in POAG: effects on IOP and ocular blood flow. AB - The scope of this work was to evaluate the effect on ocular pressure and on ocular blood flow of latanoprost 0.005% eyedrops. Included in the study were 12 patients (24 eyes) with POAG, aged between 37 and 48 years, non-smokers, refractions between +/- 3D. Haemorrheological parameters within normal, not in ocular or systemic vasoactive therapy. Each patient had one eye treated with latanoprost 0.005% and the other with timolol 0.05%. The choroidal perfusion was measured by Langham's POBF system during the first day of therapy and then after 7, 15, 30, 60, 90 and 180 days. The maximum pressure decrease after the first administration of latanoprost was at the twelfth hour; after 6 months of therapy, mean IOP reduction was 32.6%. POBF values increased up to 55.8% in the first day and then settled at 22.6% at the end of the study. Timolol showed a similar pressure progress, but its haematic perfusion values were distinctly lower. In conclusion, latanoprost is efficacious in POAG therapy since it unites a positive optic nerve head perfusion effect with hypotensive efficacy. PMID- 9972342 TI - Fatty acid use in glaucomatous optic neuropathy treatment. AB - The authors have studied the efficacy of an association of DHA, vitamin E and vitamin B complex (TROFINERV) in glaucomatous patients. The parameters evaluated were computerized visual field (CVF) and retinal contrast sensitivity (RCS). Thirty chronic simple glaucoma patients in good tensional compensation with local therapy were given TROFINERV oral therapy. The results show significant differences after 90 days of treatment both in the perimetric indices (MD, SF, CPSD; p < 0.05) and in the RCS frequency values (p < 0.05). In the light of the results obtained, the authors consider the use of such association to be a useful support in glaucomatous patient therapy for preventing or delaying the progress of damage. PMID- 9972343 TI - Evaluation of the efficacy of nicergoline on blood flow and ocular function in patients affected by chronic simple glaucoma. PMID- 9972344 TI - Relationship between cefalo-ophthalmic haemodynamics and visual function in patients affected by carotid stenosis. Possible links with critical low tension glaucoma pictures. PMID- 9972345 TI - Ocular functionality variations after endarterectomy. PMID- 9972346 TI - Cyclosporine C: a study of wound-healing modulation after trabeculectomy in rabbit. AB - The authors studied the clinical and histological effects of cyclosporine instilled after filtering surgery. Its efficacy and variety of advantages compared to other antimitotic agents encourage its use. PMID- 9972347 TI - Trabeculectomy and phacoemulsification: one-way and two-way approach compared after one year. PMID- 9972348 TI - Viscocanalostomy: a pilot study. PMID- 9972349 TI - Glaucoma and quality of the life. AB - A questionnaire was prepared and given to 332 subjects who passed through our Institute for Glaucoma with the aim of evaluating their quality of life. The diagnosis of glaucoma is associated with a diminished quality of life in a considerable percentage of the interviewed subjects. The patients are troubled most of all by the inconvenience of the treatments and the fear of visual compromission. Mitotic therapies, polytherapies and systemic therapies are the less agreeable of them. Of the therapy in itself, the most disagreeable aspects are the frequency and timetable of the medications. No quality of life differences were mentioned by surgically treated patients nor those on solely pharmacological treatment. PMID- 9972350 TI - The "personality" of the glaucomatous patient: preliminary results. PMID- 9972351 TI - [Pollution and allergy: a relationship that needs proof]. PMID- 9972352 TI - [Pollution and allergy: the contributions of animal and in vitro experimentation]. AB - The respiratory pathological symptoms induced by atmospheric pollutants are closely dependent on the action of the aerocontaminants on the cells of the respiratory tract that are exposed to their effects. Two methods of experimental investigation are used to specify the effects of pollutants on the respiratory system: Study of the morphological and functional alterations of animal respiratory systems after exposure to different pollution constituents. Exposure of bronchitic or pulmonary cells to microquantities of pollutants, using different techniques that create direct contact between the pollutant and target cells. In animals gaseous pollutants alter the means of defence (muco-ciliary purification and antibacterial defence), inducing development of a neutrophil inflammatory reaction and, for ozone and NO2 favouring sensitisation by allergen dependent IgE; diesel particles are responsible for restrictive ventilation problems, an inflammatory reaction, a sensitisation develops to pneumoallergens and in some cases of the development of pulmonary tumours. In vitro studies specify the cellular mechanisms and the molecules that are responsible for the observed phenomena: increase in the synthesis and expression of messenger DNA the codes for the pro-inflammatory cytokines, adherance molecules and chimiokines. PMID- 9972353 TI - [Experimental studies of the effects of atmospheric pollutants]. AB - Experimental studies in man are an indispensable complement to epidemiological studies and experimental studies on animals. They aim at understanding the mechanisms of action of the main pollutants and at knowing their thresholds of triggering of the acute effects on the respiratory system. The studies made in man involve controlled exposure to different atmospheric pollutants, with measurement of the functional respiratory repercussions, studies of modification of the cells in broncho-alveolar lavage, as well as experimental protocols that combine inhalation of allergen and exposure to atmospheric pollutants by allergic subjects. The main results that are available are reported to distinguish those from normal subjects and those who are allergic. More recent protocols are based on exposure to concentrations that are close to atmospheric concentrations or those that are met in work places. The main data in the literature are reported in this journal and concern SO2 acid aerosols, dioxides of nitrogen, ozone and diesel particles. Pathogenic hypotheses concerning the undesirable effects of atmospheric pollutants on the respiratory system are considered. PMID- 9972354 TI - [Inter-relationship between allergenic pollens and air pollution]. AB - Morbidity to pollens is increasing in the French population. Pollen is the vector of the male genome of the plant. It is the wind-borne pollens that are the most allergenic by release of allergen molecules that make contact with the mucosae. So every individual who is genetically allergic (atopic) may develop rhinitis and/or conjunctivitis and/or asthma.... More than 200 allergens have been identified, of which the three-dimensional structure is well-known. The urban pollution that is specific to a quarter under consideration (residential zone, pedestrianised, mid-town roadway and industrial zone) plays an important role in morbidity to pollen allergy. A significant coating of pollens is to be found on urban roads. Pollen sensitisation is increased by exposure to pollutants from 24 to 48 hours. The pollutants seem to make the surface of the exine more fragile, so triggering a mucosal reaction, making them more exposed to pollen allergens. The pollutant also plays the role of an adjuvant to the pollen allergen, and so is the origin of a greater production of IgE. PMID- 9972355 TI - [Pollution and allergy: the epidemiological data]. AB - This area is controversial, mostly because of disagreement between experimental and epidemiological data. Even though modulation of asthma by the level of atmospheric pollution has been well shown by panel and ecological studies, the relationship between pollution and genesis of allergic diseases has not been confirmed by epidemiological studies. Comparison of the frequency of asthma in urban and rural surroundings in general shows, in the urban environment, an advantage of irritation symptoms but not for asthma. In contrast, the prevalence of atopy seems higher in the urban environment, which is perhaps a reflection of a different way of life, like that shown in east-west studies. Several recent investigations showed that at the centre of a development additional respiratory symptoms related to the intensity of automobile traffic, but no relationship was shown with atopy. In the same way, no epidemiological investigation has shown a relationship between automobile pollution and prevalence of atopy. Thus, at present no solid elements exist to support an increase of the frequency of asthma and especially atopy, in a relationship with modern atmospheric pollution, essentially of automobile origin. PMID- 9972356 TI - [Justification of the survey]. PMID- 9972357 TI - [Methodology of the survey]. PMID- 9972358 TI - [Anesthetics according to characteristics of patients, establishments and indications]. PMID- 9972359 TI - [Organization and techniques of anesthesia]. PMID- 9972360 TI - [Anesthetics in surgery]. PMID- 9972361 TI - [Anesthetics in obstetrics]. PMID- 9972362 TI - [Anesthetics excluding surgery and obstetrics]. PMID- 9972363 TI - [Anesthetics for emergencies]. PMID- 9972364 TI - [Anesthetics for ambulatory patients]. PMID- 9972365 TI - [Anesthetics and transfusion practices]. PMID- 9972366 TI - [Synthesis and future prospects]. PMID- 9972367 TI - Preoperative evaluation of the chemosensitivity of breast cancer by means of double phase 99mTc-MIBI scintimammography. AB - The chemosensitivity of breast cancer is important for its management, but it is difficult to evaluate preoperatively. Tc-99m hexakis-2-methoxyisobutylisonitrile (MIBI) scintimammography has been reported to indicate the expression of P glycoprotein, which is one factor concerned with multidrug resistance. We developed a chemosensitivity assay by using surgical specimens to investigate whether 99mTc-MIBI scintimammography findings before the operation are related to chemosensitivity according to our assay. Fifteen patients with primary breast cancer were enrolled into the study. Early and delayed images were obtained at 10 and 120 minutes after intravenous injection of 99mTc-MIBI, respectively. Regions of interest were placed on the tumors and the contralateral healthy breasts in each patient to estimate 99mTc-MIBI uptake in the tumor, and retention indices were then calculated to assess the washout of 99mTc-MIBI. Chemosensitivity assay was performed by incubating surgical specimens with anticancer agents such as doxorubicin, epirubicin, pinorubicin, mitomycin C, cisplatin and 5-fluorouracil. 99mTc-MIBI washout on scintimammography was successfully related to inhibition ratios on chemosensitivity tests when compared with 99mTc-MIBI uptake by the tumor. In particular, high correlation coefficients were obtained between the retention index of 99mTc-MIBI and the inhibition ratios of doxorubicin (r = 0.75), epirubicin (r = 0.60) and pinorubicin (r = 0.62), but poor correlation was found for mitomycin C (r = 0.44) and cisplatin (r = 0.31). Our results indicate that the retention index of 99mTc-MIBI is closely correlated to chemosensitivity to anthracyclines, suggesting that double-phase scintimammography allows preoperative prediction of chemosensitivity of breast cancer. PMID- 9972368 TI - Kinetics of 111In-labeled bleomycin in patients with brain tumors: compartmental vs. non-compartmental models. AB - The kinetics of an indium-111 labeled bleomycin complex (111In-BLMC) after rapid intravenous injection in patients with brain tumors was quantified by using compartmental and non-compartmental models. The models were applied to data obtained from 10 glioma, one meningioma, and one adenocarcinoma brain metastasis patients. Blood and urine samples from all the patients and tumor samples from three patients were collected. The mean transit time of 111In-BLMC in the plasma pool was 14 +/- 7 min without and 1.8 +/- 0.6 h when accounting for recirculation, and 13 +/- 4 h in the total body pool. The mean plasma clearance of 111In-BLMC was 0.3 +/- 0.1 m/blood/min and the mean half-life in urine was 3.5 +/- 0.6 h. The mean transfer coefficients for the open three-compartmental model were: excretion from plasma = 0.02 +/- 0.01, from depot to plasma = (12 +/- 9)*10(-4), from plasma to depot = 0.01 +/- 0.01, from tumor to plasma = 0.39 +/- 0.19 and from plasma to tumor = 1.11 +/- 0.57, all in units minute-1. The mean turnover time from the tumor was 4.5 +/- 2.7 min and from the depot 20 +/- 8 h. It is concluded that both compartmental and non-compartmental models are sufficient to describe the kinetics of indium-111 labeled bleomycin complex. The non-compartmental model is more practical and to some extent more efficient in describing the in vivo behaviors of 111In-BLMC than the compartmental model. The compartmental model used provides estimates of both extraction and excretion from the plasma and tumor. PMID- 9972369 TI - 123I-MIBG myocardial scintigraphy in diabetic patients: relationship with 201Tl uptake and cardiac autonomic function. AB - PURPOSE: To investigate the influence of diabetic myocardial damage (suspected myocardial damage; SMD) diagnosed by 201Tl-SPECT and diabetic cardiac autonomic neuropathy (AN) on myocardial MIBG uptake in patients with non-insulin-dependent diabetes mellitus (NIDDM). SUBJECTS AND METHODS: Eighty-seven diabetic patients divided into four subgroups: 23 with SMD (+) AN (+); 19 with SMD (+) AN (-); 27 with SMD (-) AN (+); 18 with SMD (-) AN (-), and 10 controls were studied. Both planar and SPECT images were taken at 30 minutes (early) and 3 hours (delayed) after 123I-MIBG injection. The heart to mediastinum uptake ratio (H/M) and washout ratio of 123I-MIBG (WR) were obtained from both planar images. On SPECT images, the total uptake score (TUS) was obtained by the 5 point score method by dividing the myocardium into 20 segments on visual analysis. Similarly, the difference between the 201Tl image and the 123I-MIBG image in TUS was taken as the difference in the total uptake score (delta TUS) representing cardiac sympathetic denervation without SMD. RESULTS: On both early and delayed planar images, the mean H/M value in the subgroups of diabetic patients was significantly lower in the SMD (+) AN (+) group than in the control group, but among those subgroups, there was statistically significant difference between the SMD (+) AN (+) and SMD (-) AN (-) groups only on the delayed images. Regarding the WR value, there was no statistically significant difference among subjects. On SPECT image analysis, the diabetic subgroup with AN or SMD had statistically significant lower values for TUS than those of the control group. Among diabetics, there was a statistically significant differences between SMD [+] AN [+] and SMD [-] AN [-] on both early and delayed images. Similarly, the SMD [+] AN [-] group also had significantly lower values than those of SMD [-] AN [-] on early images. Regarding delta TUS, there was a statistically significant differences between AN [+] subgroups and controls. Similarly, the mean value for delta TUS was much higher in AN [+] subgroups than in AN [-] subgroups with or without SMD in diabetes mellitus. CONCLUSION: 123I-MIBG myocardial uptake is affected by both SMD and cardiac autonomic neuropathy. Based on the finding that delta TUS was much higher in AN [+] subgroups and there was no statistically significant difference between SMD [+] AN [+] and SMD [-] AN [+] subgroups, a decrease in myocardial 123I-MIBG uptake might progress independently of SMD. PMID- 9972370 TI - A comparison of Tc-99m HMPAO brain SPECT images of young and aged normal individuals. AB - The purpose of this study was to examine the normal distribution patterns of 99mTc-HMPAO (HMPAO) in young and aged normal individuals and to clarify differences between the distribution patterns of the two groups by means of an anatomical standardization technique. The tracer distribution was measured with HMPAO and SPECT in 18 normal subjects; age range 20-81 yrs. SPECT images were globally normalized by averaging whole brain radioactivity counts to 100 counts/voxel. The SPECT images for each subject were transformed into the standard brain anatomy by means of a computerized brain atlas, together with each subject's CT images. Mean and SD images for young (28.8 +/- 6.4 yrs) and aged groups (62.3 +/- 10.2 yrs) were then calculated on a voxel-by-voxel basis. Statistically significant differences between young and aged groups were observed in the relative tracer distribution patterns. In the aged group, relative decreases were found in the cortical areas of the frontal and temporal lobes, limbic areas and basal ganglia regions. The results, as visualized changes in tracer distribution patterns with aging, may contribute to more accurate clinical diagnosis. PMID- 9972371 TI - Predicting the effects on patients with dilated cardiomyopathy of beta-blocker therapy, by using iodine-123 15-(p-iodophenyl)-3- R,S-methylpentadecanoic acid (BMIPP) myocardial scintigraphy. AB - We examined whether the iodine-123 15-(p-iodophenyl)-3- R,S-methylpentadecanoic acid (BMIPP) myocardial scintigraphy was useful for predicting the treatment response to beta-blocker in patients with dilated cardiomyopathy (DCM). Sixteen patients with DCM were studied. BMIPP single photon emission computed tomography (SPECT) was performed before beta-blocker therapy. The count ratio of the heart (H) to the upper mediastinum (M) (H/M ratio) was calculated. Several measurements including the BMIPP H/M ratio before the administration of metoprorol were retrospectively compared among the 10 "good responders" (showing improvement by at least one NYHA class or an increase in the ejection fraction of > or = 0.10, 6 months after the start of the drug therapy) and the 6 "poor responders." The bull's eye map of BMIPP was divided into 17 areas. Each segmental score was analyzed quantitatively by means of a two-point scoring system (good uptake > or = 67%, poor uptake < 67%). The total score was regarded as the uptake score. The H/M ratio was significantly higher in the good responders than in the poor responders (2.41 +/- 0.24 vs. 1.86 +/- 0.17 p < 0.01). There were no significant differences between the two groups in any other variable data at entry. The uptake score was also a good index for predicting the therapeutic effect. When a relative uptake of 67% or higher was scored as 1, uptake scores of 9 to 17 corresponded to good responses (sensitivity = 100%, specificity = 100%, accuracy = 100%, positive and negative predictive value = 100%). Although the number of patients studied is small, our results suggests that BMIPP myocardial scintigraphy can predict the response to a beta-blocker in patients with DCM. PMID- 9972372 TI - Effects of diltiazem on myocardial perfusion abnormalities during exercise in patients with hypertrophic cardiomyopathy. AB - The effect of diltiazem on myocardial ischemia in patients with hypertrophic cardiomyopathy (HCM) was evaluated by exercise myocardial 201Tl single photon emission computed tomography (SPECT). Exercise myocardial SPECT was performed before and 8 weeks after oral administration of diltiazem (180 mg/day) in 20 patients with HCM who showed transient perfusion defects on exercise myocardial 201Tl SPECT under control conditions. SPECT images were divided into 17 segments. The 201Tl perfusion defects were visually scored and evaluated as the defect score. The transient dilation index was calculated as an index of subendocardial ischemia. Improvement of the defect score was demonstrated in 15 patients after the administration of diltiazem. The mean defect score decreased significantly from 9.90 +/- 5.17 to 5.50 +/- 4.89 (p < 0.0001). Although 16 of 20 patients showed an abnormal transient dilation index before diltiazem treatment, 16 showed improvement and 13 of these normalized after diltiazem therapy. The mean transient dilation index decreased from 1.16 +/- 0.10 to 1.02 +/- 0.09 (p < 0.0001). In conclusion, diltiazem prevents or diminishes myocardial ischemia in patients with HCM. PMID- 9972373 TI - 201Tl SPECT as an indicator for early prediction of therapeutic effects in patients with non-small cell lung cancer. AB - This study retrospectively investigated the good parameters on thallium-201 chloride (201Tl) SPECT for early assessment of the therapeutic effects in patients with non-small cell lung cancer. Based on tumor response as determined by chest CT scan about 9 weeks after the end of irradiation with adjuvant chemotherapy, the subjects were divided to the responder group (tumor regression > 50%, n = 13) and non-responder group (tumor regression < 50%, n = 13). 201Tl SPECT was performed before and at the halfway through the course of therapy (average tumor dose, 27.4 Gy +/- 4.5) in all the patients. SPECT was conducted twice 15 min (early scan) and 120 min (delayed scan) after intravenous injection of 148 MBq (4 mCi) of 201Tl. Tumor-to-contralateral normal lung tissue count ratios on both scans were calculated as early and delayed uptake ratios (EUR and DUR), and a retention index (RI) was also derived from these ratios. In the responder group, a significant decrease in DUR and RI halfway through the therapy was observed compared to pretreatment (2.6 +/- 0.6 vs. 3.5 +/- 1.0; p < 0.01, and -2.3% +/- 25.5 vs. 37.4% +/- 17.8; p < 0.001, respectively), even though EUR did not change significantly (N.S.). By contrast, in the non-responder group, there were no significant changes in any of these parameters (N.S.). When comparing DUR and RI for the two groups halfway through the therapy, DUR and RI were significantly lower in the responder group (both; p < 0.01), but no significant difference was noted in EUR (N.S.), and the percent reduction in tumor size did not correlate with the percent decrease in DUR or RI (N.S.). These results indicate that the extent of decrease in DUR and RI after therapy can be a useful parameter for early assessment of the therapeutic effects in patients with non small cell lung cancer. PMID- 9972374 TI - Glucose tolerance and myocardial F-18 fluorodeoxyglucose uptake in normal regions in coronary heart disease patients. AB - To elucidate the relation between glucose tolerance and myocardial uptake of F-18 fluorodeoxyglucose (FDG), FDG-PET with 75 g oral glucose loading was performed on 43 coronary artery disease patients (twice in 2 patients). The patients were divided into 4 groups based on the blood glucose level (BS) and the insulinogenic index (II): group 1, normal (n = 9); group 2, impaired glucose tolerance (IGT, n = 12); group 3, mild diabetes mellitus (DM) (II > 0.4, n = 12); and group 4, severe DM (II < or = 0.4, n = 12). Percent (%) dose uptake of FDG in the normal regions of the myocardium was not significantly different in groups 1, 2, and 3, but it was much lower in group 4 than in groups 1 and 2. In groups 2, 3, and 4, % dose uptake showed a definite negative correlation with BS 60 min after glucose loading (r = -0.450, p < 0.05), and a close positive correlation with II (r = 0.363, p < 0.05). These findings indicate that myocardial FDG uptake in normal regions is not greatly impaired in patients with IGT or mild DM. Myocardial viability can be assessed by oral glucose loading in patients with IGT and mild DM as well as in patients with normal glucose tolerance. PMID- 9972375 TI - Quantitative evaluation of the regional hepatic reserve by 99mTc-GSA dynamic SPECT before and after chemolipiodolization in patients with hepatocellular carcinoma. AB - 99mTc-DTPA-galactosyl human serum albumin (99mTc-GSA) hepatic scintigraphy was performed in 32 patients with hepatocellular carcinoma before and after chemolipiodolization, which was performed from the right hepatic artery (RHA) in 15 patients and the proper hepatic artery (PHA) in 17 patients. Following a bolus injection of 99mTc-GSA, dynamic SPECT was performed with 1 minute rotation for 16 minutes. Data analysis was conducted by setting a region of interest (ROI) on the right liver, left liver and heart and then their time-activity curves were generated. The regional hepatic accumulation index (LHL15) and the regional uptake constant index (KU) were also calculated from the time-activity curves. In the RHA group, regional LHL15 and KU of the left lobe significantly increased, but they did not significantly increase in the PHA group. In the right lobe, no significant change in regional KU or LHL15 was observed. In the poor prognosis group, all indices in both regions decreased after chemolipiodolization, especially the value for regional KU had a poor score before chemolipiodolization. A decrease in each index in both lobes after chemolipiodolization is considered to be a sign of a poor prognosis. 99mTc-GSA dynamic SPECT scintigraphy is a useful method for evaluating the changes in regional hepatic reserve before and after chemolipiodolization. PMID- 9972376 TI - Usefulness of per-rectal portal scintigraphy with Tc-99m pertechnetate for galactosemia in infants. AB - Galactosemia discovered by newborn screening is rarely caused by enzyme deficiency. It has recently been reported that among patients without enzyme deficiency portosystemic shunting may be a cause of galactosemia in some patients. We did per-rectal portal scintigraphy in patients with such galactosemia detected during screening of newborns to examine the usefulness of this method for the diagnosis of portosystemic shunts via the inferior mesenteric vein. The subjects were eight neonates with galactosemia without enzyme deficiency detected during screening. A solution containing technetium-99m pertechnetate was instilled into the rectum, and serial scintigrams were taken while radioactivity curves for the liver and heart were recorded sequentially. The per-rectal portal shunt index was determined by calculating the ratio for counts of the liver to counts for the heart integrated for 24 seconds immediately after the appearance of the liver time-activity curve. A portosystemic shunt was detected in both of the patients with a shunt index of 30% or more, but not in the six patients with a shunt index less than 30%. The blood galactose levels of these six patients later entered the reference range. This method is noninvasive and there is little exposure to the radionuclide. It seemed to be useful for the diagnosis of portosystemic shunt in newborns with galactosemia without enzyme deficiency. PMID- 9972377 TI - Evaluation of amlodipine dosing for conversion of nifedipine extended-release to amlodipine in the treatment of hypertension. AB - OBJECTIVE: To evaluate the appropriate dosing of amlodipine when converting patients from nifedipine extended-release (nifedipine ER) to amlodipine in the treatment of hypertension. METHODS: Patients of the Outpatient Clinic of Cheyenne Veterans Affairs Medical Center, Wyoming, receiving nifedipine ER for the management of hypertension (systolic BP or SBP > 140 mm Hg and diastolic BP or DBP > 90 mm Hg), participated in this study. Nifedipine ER was changed to amlodipine on entry into this study. An inclusion criterion was the BP had to be under control (SBP < 140 mm Hg and DBP < 90 mm Hg) before the switch. The BP in each study patient was monitored once weekly (once every 2 wk in some patients) for a total of six clinic visits or until BP was under control. Dosing titration of amlodipine was required in 16 of 27 patients after the switch. To assess the adequacy of the conversion, the statistical significance of the difference of the mean BP values before and at the end of the monitoring period was estimated by using the t-test for paired data. RESULTS: Twenty-seven male patients completed this study. BP in all study patients was adequately controlled after nifedipine ER was switched to amlodipine. The SBP and DBP values before and after the switch were similar (SBP: 124 +/- 12 vs. 126 +/- 9 mm Hg, CI of the mean difference 6.10 to 1.80; DBP: 76 +/- 8 vs. 76 +/- 7 mm Hg, CI of the mean difference -2.45 to 3.63). Initial amlodipine dose of 5 or 10 mg once daily was used in our study. No serious adverse effects were observed in any of the study patients after the drug switch. CONCLUSIONS: This study indicates the amlodipine dosage of 5 or 10 mg once daily can be used when nifedipine ER is converted to amlodipine in the treatment of hypertension. Dosage titration of amlodipine may be required to obtain adequate control of BP. PMID- 9972378 TI - Economic impact of a drug information service. AB - OBJECTIVE: A cost-avoidance model was developed to determine potential cost savings or "avoidance" that results from a drug information service (DIS) responding to drug information requests. DESIGN: Patient-specific questions received by the DIS were reviewed and evaluated. A panel determined whether a drug misadventure event may have occurred if the DIS had not been consulted. Potential outcomes from drug information requests were classified using a decision-tree model. A severity rating was then attached to each applicable request to predict potential cost savings of the DIS. RESULTS: Seventy-seven of the 570 drug information responses received in the six-week study period had assessable potential cost savings to the institution. During the study interval, potential cost savings were estimated to be $195,000. Projected to one year, potential cost savings reached $1.7 million. Of the savings noted, most were attributable to prevention of increased monitoring or additional treatment. Using a sensitivity analysis, annual potential cost savings ranged from $417,792 to $2,052,740 per year. Based on the estimated annual costs related to maintaining a DIS of $145,950, the resultant range of benefit/cost ratio is 2.9:1 to 13.2:1. CONCLUSIONS: This model demonstrates that the DIS at our institution provides potential cost savings. This model may be modified to evaluate potential cost savings in other areas of pharmacy practice. PMID- 9972379 TI - Characterization of rash with indinavir in a national patient cohort. AB - OBJECTIVE: To characterize indinavir-associated rash using systematic data collection through postmarketing surveillance in a sample of HIV/AIDS patients. DESIGN: HIV-infected patients identified through a medication counseling line who reported onset of a rash following initiation of indinavir therapy were included in this case series analysis. Pertinent information regarding onset, description, and management of rash; other medications initiated within two weeks of indinavir or rash onset; and medication allergy history was obtained through follow-up telephone contact. Patients were contacted weekly until the rash resolved or indinavir was discontinued. SETTING: Stadtlanders Drug Distribution Company, located in Pittsburgh, PA. RESULTS: Of the 110 patients identified and followed, 67% reported rash onset within two weeks of initiating indinavir therapy. The rash was initially localized in all 110 patients and subsequently spread to other areas of the body in 77% of the patients. The rash spread to the full body in 44% (49) of the patients. The rash was accompanied by pruritus in 86% of the patients, and the majority of patients (87%) were afebrile. Eighty-one patients received treatment with medications such as antihistamines or oral or topical corticosteroids. Fifty percent of patients receiving treatment for the rash reported that these medications were helpful in relieving rash symptoms. Fifty nine percent of the patients continued indinavir therapy despite the occurrence of rash. CONCLUSIONS: Results from this study suggest that indinavir-associated rash occurs within two weeks of initiation of therapy for the majority of patients. Typically, the rash is localized with subsequent spread and is associated with pruritus. The majority of patients are able to continue indinavir therapy despite the occurrence of rash. PMID- 9972380 TI - Torsade de pointes induced by cisapride/clarithromycin interaction. AB - OBJECTIVE: To highlight a case of torsade de pointes ventricular arrhythmia induced by the concomitant use of cisapride and clarithromycin. CASE SUMMARY: A 77-year-old white woman was admitted to the hospital with a diagnosis of pneumonia and exacerbation of congestive heart failure. In addition to her usual medications, which included cisapride, the patient was prescribed trimethoprim/sulfamethoxazole and clarithromycin for pneumonia. Within 48 hours, the patient had documented episodes of symptomatic torsade de pointes arrhythmia, which eventually responded to therapy. Both cisapride and clarithromycin were discontinued, and the patient did not have any recurring episodes during a 32 month follow-up. DISCUSSION: Cisapride has been implicated in causing adverse cardiac events, including torsade de pointes arrhythmia. In most cases, the patients had preexisting risk factors for torsade de pointes and/or were receiving other medications known to inhibit the hepatic CYP3A4 enzyme system and the metabolism of cisapride. There is evidence that clarithromycin, a relatively new macrolide antibiotic, also inhibits the isoenzyme CYP3A4. The resulting accumulation of cisapride caused by concomitant clarithromycin therapy was believed to have been the cause of the torsade de pointes arrhythmia in this patient. CONCLUSIONS: Concomitant use of cisapride and clarithromycin may cause torsade de pointes arrhythmia. PMID- 9972381 TI - Pill-induced esophagitis caused by oral rifampin. AB - OBJECTIVE: To report a case of pill-induced esophagitis caused by oral rifampin. DATA SOURCES: English-language references identified via a MEDLINE search from January 1966 to May 1998 and a bibliographic review of pertinent articles. DATA SYNTHESIS: A large number of oral medications have been reported to cause pill induced esophagitis. This case represents the second report attributed to rifampin. A 70-year-old white man receiving vancomycin, gentamicin, and oral rifampin for treatment of Staphylococcus epidermidis prosthetic valve endocarditis reported dysphagia immediately after swallowing a rifampin capsule on the fourth day of therapy. The following day, fiberoptic laryngoscopy and esophagoscopy demonstrated a red capsule partially embedded in the neopharynx. A day later, upper esophageal obstruction consistent with edema related to pill induced esophagitis was identified by barium swallow. Following the procedure, the patient was placed on total parenteral nutrition and took nothing by mouth. Sixteen days after first reporting dysphagia, he was placed on a full liquid diet. Several factors may have increased the patient's risk for pill-induced esophagitis, including age, bedridden state, gastroesophageal reflux disease, simultaneous administration of several medications, and neopharyngeal stricture. CONCLUSIONS: Oral rifampin may cause esophagitis. Healthcare providers should be alert to the possibility of pill-induced esophagitis in susceptible patients. Patients with predisposing factors for the development of pill-induced esophagitis should be educated about proper swallowing of oral medications. PMID- 9972382 TI - Quinine-induced hepatotoxicity. AB - OBJECTIVE: To report a case of quinine-induced hepatotoxicity presenting within 24 hours following the ingestion of the first dose. DATA SOURCES: Case report information was obtained from the medical record, the patient, and the physicians involved in this patient's case. MEDLINE and Index Medicus were searched to obtain relevant published literature from January 1942 to May 1997 using the terms quinine, muscle cramps, liver disease, and hepatotoxicity. CASE SUMMARY: A 57-year-old Native American woman presented with symptoms of nausea, vomiting, generalized myalgia, headache, fever, chills, and rigor. The alkaline phosphatase, lactate dehydrogenase, aspartate aminotransferase, alanine aminotransferase, and gamma-glutamyltranspeptidase concentrations were dramatically elevated. Quinine was suspected as the cause after several days of hospitalization and continued therapy. With discontinuation of the quinine, the patient's symptoms resolved within 48 hours and the liver enzyme concentrations declined within 72 hours. CONCLUSIONS: Documented hepatotoxicity has occurred with quinidine, the optical isomer of quinine. Limited awareness of quinine induced hepatotoxicity may result in an unrecognized adverse effect. PMID- 9972383 TI - Reversible nonthrombocytopenic palpable purpura associated with metoclopramide. AB - OBJECTIVE: To report a case of reversible nonthrombocytopenic palpable purpura associated with metoclopramide. CASE SUMMARY: A 72-year-old white man was admitted for worsening palpable purpura over a two-day period. Two days prior to admission, metoclopramide 10 mg orally three times per day was started for a gastrointestinal condition. Upon admission, all drugs were continued except metoclopramide. Over the next two days, the purpura began to resolve. Platelet count was within normal limits on admission and the patient developed no serious consequences because of the purpura. DISCUSSION: According to the literature, reversible nonthrombocytopenic palpable purpura has not been previously reported with metoclopramide. A search of MEDLINE (1966 to November 1998) and International Pharmaceutical Abstracts (1970 to November 1998) did not reveal a similar case. Although a rechallenge was not tried, this case appears to demonstrate a temporal relationship between the initiation and discontinuation of metoclopramide and the onset and resolution of symptoms. Similar cases of this reaction have been reported with procainamide, which is structurally similar to metoclopramide. CONCLUSIONS: Metoclopramide may cause reversible nonthrombocytopenic vascular-type palpable purpura. Discontinuation of the drug appeared to be responsible for the resolution of symptoms. PMID- 9972384 TI - Ibutilide: an antiarrhythmic agent for the treatment of atrial fibrillation or flutter. AB - OBJECTIVE: To discuss the clinical pharmacology of the antiarrhythmic drug ibutilide in patients with atrial fibrillation (AF) or atrial flutter (AFl). DATA SOURCES: A MEDLINE search (January 1983-December 1997) was used to identify pertinent English-language articles on ibutilide. Key search terms included ibutilide, AF, AFl, cardioversion, and sinus rhythm. The MEDLINE search was supplemented by references included in the bibliographies of comprehensive review articles and studies. STUDY SELECTION: Studies and review articles describing the chemistry, pharmacology, and pharmacokinetics of ibutilide were selected. All abstracts and published clinical trials evaluating the efficacy and safety were reviewed. DATA EXTRACTION: Pertinent information on the pharmacology and mechanism of action of ibutilide was summarized. Data were extracted from the clinical trials describing trial design, patient population, interventions, methods of evaluation, outcomes, and statistical significance. DATA SYNTHESIS: Ibutilide is a Vaughan-Williams class III antiarrhythmic agent approved for intravenous use for the rapid termination of recent-onset AF or AFl. The drug is extensively metabolized by the liver, has a volume of distribution of 11-15 L/kg, is 40% protein bound, and has an elimination half-life of 6 hours (range 2-12). Data from two placebo-controlled trials demonstrated the efficacy of ibutilide for converting AF or AFl of short duration (< or = 90 d) to normal sinus rhythm. A third placebo-controlled trial demonstrated efficacy in patients who developed AF or AFl following cardiac surgery. Comparative trials with procainamide and sotalol have shown at least similar and perhaps superior efficacy with ibutilide. There are no comparative trials with other antiarrhythmic drugs or with direct current cardioversion (DCC). In 586 clinical trial patients receiving ibutilide, the most significant adverse effect was the development of torsade de pointes in 25 patients (4.3%) including 10 cases (1.7%) in which the rhythm was sustained. All cases of torsade de pointes were terminated electrically and none resulted in death or severe morbidity. No prospective cost-effectiveness studies are available; however, results from two decision models suggest that ibutilide may have advantages over other drugs and first-line electrical cardioversion. CONCLUSIONS: Ibutilide appears to be an effective alternative method for rapid conversion of recent-onset AF or AFl. The drug may be particularly useful in patients who have undergone recent cardiac surgery or those who are not ideal candidates for DCC. Although studies suggest that the risk of proarrhythmia and in particular torsade de pointes is relatively low, caution is advised until additional experience is gained in clinical practice. PMID- 9972385 TI - Trovafloxacin: a new fluoroquinolone. AB - OBJECTIVE: To review the pharmacology, antimicrobial activity, pharmacokinetics, clinical efficacy, and safety of trovafloxacin. DATA SOURCES: A MEDLINE search (January 1966-April 1998) was conducted for relevant literature using the terms CP-99,219, CP-116,519, trovafloxacin, and alatrofloxacin. Abstracts published by the American Society of Microbiology during 1995-1997 meetings were also reviewed. STUDY SELECTION AND DATA EXTRACTION: All in vitro, animal, and human studies were reviewed for the antimicrobial activity, pharmacokinetics, efficacy, and safety of trovafloxacin. DATA SYNTHESIS: Trovafloxacin is a new fluoroquinolone with enhanced activity against gram-positive and anaerobic microorganisms. The oral bioavailability under fasting conditions is approximately 88%. The elimination half-life of trovafloxacin is approximately 10 hours. Less than 10% of trovafloxacin is eliminated unchanged in the urine. Trovafloxacin is effective in the treatment of community-acquired pneumonia and nosocomial pneumonia with cure rates of > 90% and 77%, respectively. Trovafloxacin is comparable with ceftriaxone in the treatment of meningococcal meningitis in children; each produces a cure rate of approximately 90%. In treatment of uncomplicated urinary tract infection, both ciprofloxacin and trovafloxacin achieve an eradication rate of > or = 93%. Trovafloxacin is similar to ofloxacin in the treatment of urogenital Chlamydia trachomatis and acute exacerbations of chronic bronchitis, with clinical success in 97% of patients with each drug. The common adverse effects of trovafloxacin include dizziness, headache, and gastrointestinal intolerance. CONCLUSIONS: The advantages of once daily dosing and enhanced activity of trovafloxacin against gram-positive and anaerobic organisms may expand its use over available fluoroquinolones. Further studies are needed to define its role in the treatment of various infectious diseases. PMID- 9972386 TI - Medication-induced headache: overview and systematic review of therapeutic approaches. AB - OBJECTIVE: To review medication-induced headache (MIH) through a systematic evaluation of the literature regarding the pharmacologic management of this condition. METHODOLOGY: To identify and evaluate all pharmacologic interventions for MIH, we conducted a qualitative systematic review of the English-language literature from 1966 to June 1998 using MEDLINE. The following search terms were used: chronic daily headache, transformed migraine, analgesic withdrawal headache, analgesic rebound headache, drug-associated headache, medication induced headache, detoxification, and dihydroergotamine. In addition, a review of the references from relevant literature was also conducted to collect reports not identified in the MEDLINE search. RESULTS: Numerous therapies for acute management of MIH have been evaluated, although no rigorously conducted clinical trials were identified. Therapies evaluated include abrupt withdrawal of analgesics, initiation of dihydroergotamine, nonsteroidal antiinflammatory agents, methylergonovine, dihydroergotamine, sumatriptan, amitriptyline, dexamethasone, piracetam, prothipendyl, and valproate. Epidemiology, diagnosis, clinical features, pathophysiology, and long-term prognosis of therapy are discussed and therapeutic guidelines are offered. CONCLUSIONS: MIH is an underrecognized and difficult condition affecting headache-prone patients. The published literature concerning treatment of patients with MIH is scant and of poor quality, making it difficult for clinicians to decide on appropriate therapy. Recognition and treatment of MIH may lead to a long-term improvement in headache relief for many patients. It appears that complete withdrawal of the medications being overused is required for favorable long-term results. PMID- 9972387 TI - Atypical antipsychotics. Part I: Pharmacology, pharmacokinetics, and efficacy. AB - OBJECTIVE: To compare the pharmacology, pharmacokinetics, and efficacy of the newer atypical antipsychotics with those of conventional agents and existing atypical agents. DATA SOURCES: Information was retrieved from a MEDLINE English literature search from July 1986 to June 1998 and by review of references. Indexing terms included neuroleptics, atypical antipsychotics, clozapine, risperidone, olanzapine, sertindole, quetiapine, and ziprasidone. STUDY SELECTION: Comparative studies were selected when possible; placebo-controlled studies were included when data were limited on newer atypical antipsychotics. DATA EXTRACTION: Emphasis was placed on properly designed clinical trials that assessed dosage, expanded efficacy, enhanced adverse effect profile, and cost. DATA SYNTHESIS: Like other atypical antipsychotics, the newer agents have an enhanced 5-hydroxytryptophan/dopaminergic receptors (5-HT2/D2) affinity ratio and undergo extensive biotransformation. Risperidone and olanzapine demonstrate more favorable efficacy/adverse effect ratios than clozapine, sertindole, and conventional antipsychotics in nonrefractory and refractory schizophrenics. Future studies will more clearly define the role of quetiapine and ziprasidone in antipsychotic therapy. CONCLUSIONS: Data from controlled trials on efficacy and extrapyramidal side effects support risperidone or olanzapine as first-line agents for the treatment of schizophrenia. Pharmacologic and pharmacokinetic factors do not distinguish between agents sufficiently for drug selection. PMID- 9972388 TI - An overview of levodopa in the management of restless legs syndrome in a dialysis population: pharmacokinetics, clinical trials, and complications of therapy. AB - OBJECTIVE: To review published literature investigating the efficacy and safety of levodopa in the management of restless legs syndrome (RLS), with emphasis on the hemodialysis population. DATA SOURCES: An English-language literature search using MEDLINE was conducted from 1966 to 1997 (key terms: restless legs syndrome, levodopa, hemodialysis). The bibliographies of all identified published articles were reviewed and cross-referenced to ensure that all possible references were identified. STUDY SELECTION AND DATA EXTRACTION: All identified human studies investigating the use of levodopa for the management of RLS in uremic and nonuremic patients were analyzed. RESULTS: The prevalence of RLS is 20-40% in patients with endstage renal disease (ESRD) and approximately 5% in the general population. Although the benefits of levodopa/(carbidopa/benserazide) in reducing the signs and symptoms of RLS are documented in nonuremic patients, evidence in patients with ESRD is less readily available. Three small (< 30 subjects) clinical trials in uremic patients provide preliminary evidence for the usefulness of levodopa/(carbidopa/benserazide) in this population. CONCLUSIONS: In general, the small amount of published literature supports the empirical use of levodopa/carbidopa as a safe and effective therapy to manage the distressing symptoms of RLS in a hemodialysis population. We also report personal observations over a 4-year period in our hemodialysis unit that support levodopa as an effective first-line therapy. We have averted suicidal ideation in two patients and frequently modified symptoms of severe sleep deprivation. The dose of levodopa/carbidopa must be individually titrated to each patient's symptomatology, and morning rebound and afternoon augmentation should be monitored. PMID- 9972389 TI - Drug-induced nightmares. AB - OBJECTIVE: To compile and assess the English-language literature on drug-induced nightmares, excluding nightmares secondary to drug withdrawal or drug-associated night terrors. DATA SOURCES: Published articles, letters, case reports, and abstracts in English were identified by MEDLINE (1966-May 1998) searches using the search term nightmares, chemically induced. Additional articles were obtained from bibliographies of retrieved articles. DATA EXTRACTION: All case reports of drug-induced nightmares were evaluated using the Naranjo algorithm for causality. Clinical studies of drugs that reported nightmares as an adverse effect were assessed for frequency of occurrence. DATA SYNTHESIS: Nightmares, defined as nocturnal episodes of intense anxiety and fear associated with a vivid, emotionally charged dream experience, are generally classified as a parasomnia. Possible pharmacologic mechanisms for drug-induced nightmares, such as REM suppression and dopamine receptor stimulation, are reviewed. However, the vast majority of therapeutic agents implicated in causing nightmares have no obvious pharmacologic mechanism. CONCLUSIONS: Assessing causality with an event such as a nightmare is difficult because of the high incidence of nightmares in the healthy population. Using qualitative, quantitative, and possible pharmacologic mechanism criteria, it appears that sedative/hypnotics, beta-blockers, and amphetamines are the therapeutic modalities most frequently associated with nightmares. These drug classes have a plausible pharmacologic mechanism to explain this effect. Dopamine agonists also have evidence of causality, with dopamine receptor stimulation as a possible pharmacologic mechanism. PMID- 9972390 TI - Benzodiazepines in the home treatment of acute seizures. AB - Prompt home treatment of dangerous seizures or upsetting relapses can prevent the effects of prolonged seizures and offer patients and their families an alternative to emergency medical treatment. The choice of benzodiazepine and route of administration should be based on patients' clinical presentation and acceptance. The challenge for the practitioner is to select the patients for whom home use of benzodiazepines will be appropriate, safe, and cost-effective. PMID- 9972391 TI - Albuterol for the treatment of hyperkalemia. PMID- 9972392 TI - No mourning for the conventional antipsychotics: the dawn of the atypical agents. AB - As Markowitz et al. explain, the atypical antipsychotics should become the first line agents for the treatment of schizophrenia. There is much to be learned about these drugs, but their displacement of the conventional antipsychotics will be a continuous process. The loss of the older drugs will not be mourned. PMID- 9972393 TI - Erythema multiforme secondary to amoxicillin/clavulanic acid exposure. PMID- 9972394 TI - Potential underreporting of intravenous phenytoin adverse events. PMID- 9972395 TI - Pregnancy outcome of women exposed to pinaverium due to a dispensing error. PMID- 9972396 TI - Photosensitive seizures associated with interferon alfa-2a. PMID- 9972397 TI - Potential interaction between warfarin and ocular chloramphenicol. PMID- 9972398 TI - Riluzole: a potential therapy for HIV dementia? PMID- 9972399 TI - Pharmacokinetics of etoposide in plasma and cerebrospinal fluid in the space left by tumor removal. PMID- 9972400 TI - Clinical significance of falsely elevated vancomycin concentrations in end-stage renal disease. PMID- 9972401 TI - FDA's FDAMA accomplishments--one year after enactment. PMID- 9972402 TI - Redefining resuscitation. PMID- 9972403 TI - Growth hormone--a panacea for aging? PMID- 9972404 TI - Alzheimer's disease: the advent of effective therapy. PMID- 9972405 TI - Tenoxicam does not alter renal function during anaesthesia in normal individuals. AB - BACKGROUND: Anaesthesia and surgery alter renal function. Inhibition of prostaglandin synthesis by non-steroidal anti-inflammatory drugs (NSAIDs) administered with anaesthesia may further compromise renal function. AIM: To study the effects of tenoxicam (NSAID) administered immediately prior to anaesthesia on renal function in normal individuals undergoing routine surgery. METHODS: A randomised single blind placebo controlled study comparing tenoxicam (40 mg intravenously) with placebo was carried out in 20 healthy (ASA I) patients undergoing lower spinal surgery. Glomerular filtration rate (GFR) was determined by creatinine clearance and renal tubular function measured as osmolar and free water clearance. RESULTS: GFR fell by 60% at the end of surgery but returned to pre-operative values by six hours post-operatively. There was no difference between placebo or tenoxicam with regard to changes in GFR. Tubular function was not altered by tenoxicam. CONCLUSIONS: Current clinical practice of using NSAIDs for post-operative analgesia in low risk individuals appears to have no adverse effects on renal function. PMID- 9972406 TI - A phase II study of liposomal doxorubicin in the treatment of HIV-related Kaposi's sarcoma. AB - OBJECTIVES: To evaluate the toxicity and clinical efficacy of liposomal encapsulated doxorubicin (DOX-SL) in the treatment of HIV-related Kaposi's sarcoma (KS). METHODS: DOX-SL 20-40mg/m2 was administered by intravenous infusion over 30-60 minutes every two weeks. Toxicity was assessed in all patients and response assessed in patients who completed two or more cycles of therapy. RESULTS: Twenty-five patients with KS were enrolled. Nine had received previous KS chemotherapy but only one prior anthracycline therapy. Eighteen patients had CD4 counts < 50/mm3. Eight had pulmonary and/or visceral KS. A total of 191 cycles were given, median 6, range 1-33. Twenty patients completed two or more cycles and were considered evaluable for efficacy. A defined response occurred in 11 patients, nine achieving a partial response and two a complete response. The median duration of response was 120 days and the median time to disease progression was 187 days. Acute toxicity was minimal, except in one patient who had generalised erythema, hypotension and diaphoresis within ten minutes of starting DOX-SL infusion. Grade 3 or 4 neutropenia occurred in 13.6 and 3.7% of cycles respectively. Neutropenic sepsis secondary to drug therapy was not reported. Alopecia and gastrointestinal symptoms were mild and infrequent. No cardiac toxicity was seen. Nine/25 patients developed HIV-associated illnesses while on study (three Pneumocystis carinii pneumonia, two systemic Cytomegalovirus infection, three cryptosporidiosis, one Mycobacterium avium intracellulare--(MAC) infection). Median survival in the evaluable patients was 219 days. CONCLUSIONS: DOX-SL is an effective and well tolerated palliative therapy in AIDS-related KS. PMID- 9972407 TI - Idiopathic steroid responsive chronic lymphocytic meningitis--clinical features and long-term outcome in 17 patients. AB - BACKGROUND: Some patients with chronic lymphocytic meningitis appear to respond to corticosteroid treatment, but investigations fail to identify the cause. The use of corticosteroids in patients with chronic meningitis is controversial and the long-term outcome is unclear. AIM: To review the long-term outcome in 17 patients with the syndrome of idiopathic steroid responsive chronic lymphocytic meningitis. METHODS: Review of patients' records and examination of surviving patients 1.5 to 17.5 years (median 8.8 years) after presentation. RESULTS: The cause of the steroid responsive chronic meningitis was found during follow up in two of the 17 patients: Wegener's granulomatosis and multiple sclerosis in one patient each. A cause was not found in the other 15 patients. Seven of these patients eventually recovered and corticosteroids were withdrawn after six weeks to six years without a recurrence of symptoms. Four patients improved transiently, but died six months to 26 years after starting treatment; in two, steroids were withdrawn a few weeks before death. Four patients had active chronic meningitis and reduction in the dose of corticosteroids was associated with a recurrence of symptoms. Leptomeningeal and brain biopsy in eight patients showed non-specific abnormalities which were not helpful in the diagnosis. CONCLUSIONS: A subgroup of patients with idiopathic chronic lymphocytic meningitis responds to corticosteroids. Leptomeningeal biopsy and long-term follow up seldom identify the underlying cause in these patients. Steroid treatment must be undertaken with caution, even after infective causes of chronic meningitis have been excluded. PMID- 9972408 TI - Characteristics and prognosis of KI-1 positive anaplastic large cell lymphoma in Asians. AB - BACKGROUND: Ki-1 positive anaplastic large cell lymphoma is a rare type of non Hodgkin's lymphoma (NHL), and has not been extensively described in Asian patients. AIM: To evaluate the clinical characteristics, prognostic factors and treatment outcome of Ki-1 positive lymphoma in an Asian community. METHODS: A retrospective analysis of all patients with CD30 antigen positive anaplastic large cell lymphoma from 1987 to 1996 in a single institution. RESULTS: Of 218 patients with NHL, ten (5%) were identified with Ki-1 positive anaplastic large cell lymphoma. Eight were Chinese, two Indians. The male:female ratio was 1.5:1, and the median age was 32 years. Seven patients presented with B-symptoms, and five had stage III/IV disease. The majority (seven of ten) was low- or low intermediate risk according to the International Prognostic Index (IPI). Four out of five cases immunophenotyped showed a T-cell origin. Five out of eight patients who received first-line combination chemotherapy achieved a complete remission. Two relapsed, with one being re-induced into a durable second remission. One patient with recurrent cutaneous lymphoma received solely radiotherapy and was disease-free at 20+ years from diagnosis. At analysis, two patients had died, five were disease-free at four, 27, 78, 89 months and 20 years respectively, and three were alive with disease. The IPI appears to have prognostic significance. CONCLUSION: Incidence and clinical characteristics in our Asian patients were similar to those described in Western populations. The IPI appears to have prognostic relevance. In approximately one-third of patients, long term survival can be achieved with standard treatment. PMID- 9972409 TI - The Medical Emergency Team (MET): a model for the district general hospital. AB - BACKGROUND: Most hospitals have a Cardiac Arrest Team, activated after cardiopulmonary arrest. The Medical Emergency Team (MET) is a newer concept, encompassing a proactive response to a wide range of emergencies with the aim of preventing irreversible organ failure and cardiopulmonary arrest. AIM: To describe the application of the MET model to the district general hospital, the spectrum of clinical conditions encountered, outcomes and administrative problems. METHOD: Data regarding each MET activation was collected prospectively. RESULTS: The MET responded to 68 calls to 63 patients in 12 months. The mean age was 60.4 years (range: neonatal to 94 years). The most common conditions leading to MET activation were chest pain (19.1%), cardiopulmonary arrest (14.7%), seizures (14.7%) and respiratory distress (13.2%). CONCLUSION: This paper demonstrates that the application of the MET model to the district general hospital improves the process of patient care. We are unable to conclude whether the MET alters morbidity or mortality for hospital inpatients. PMID- 9972410 TI - Congestive cardiac failure (CCF) as a cause of fatal stroke and all cause death. AB - BACKGROUND: Congestive cardiac failure (CCF) has been found to be a clinical risk factor for stroke in patients with non rheumatic atrial fibrillation. AIMS: To study CCF as a risk factor for stroke deaths and all cause deaths in coronary heart disease (CHD). METHODS: Case control study from a single cardiologist's practice: 370 deaths, 32 (9%) from stroke; controls of 160 and 370 consecutive patients for stroke deaths and all cause deaths respectively. Multivariate analysis using logistic regression. RESULTS: A--Stroke deaths. Positive associations for CHD with CCF, hypertension; negative association for CHD without CCF. Patients with CHD and CCF were 7.4 times as likely to die from stroke as patients with CHD without CCF. B--All cause deaths. Positive associations for CHD or cardiomyopathy with CCF, atrial fibrillation, diabetes and hypertension; negative association for CHD without CCF. Patients with CHD and CCF were 6.1 times as likely to die from all causes as patients with CHD without CCF. CONCLUSIONS: Many stroke deaths in patients with CHD and CCF may be cardioembolic in origin. A randomised controlled trial in such patients is indicated to see if anticoagulants can reduce the incidence of stroke. PMID- 9972411 TI - Percutaneous transseptal mitral valvotomy--progress report. AB - BACKGROUND: Percutaneous transseptal mitral valvotomy (PTMV) has been established as an alternative to surgery in the treatment of mitral stenosis. AIM: To review our experience in the first 200 attempted PTMV procedures in patients with mitral stenosis, and the short and medium term follow-up. METHODS: PTMV was attempted on 200 occasions in 189 patients with significant mitral stenosis between May 1988 and May 1994. There were 156 females and 33 males, mean age 53.5 years (range 14 to 83 years). Six patients were pregnant at the time of the procedure. RESULTS: Valve split was achieved at the initial attempt in 183/189 procedures (97%). Clinical improvement of at least one New York Heart Association (NYHA) functional class was achieved in 172/189 patients (91%). The mean mitral valve gradient (mean +/- SD) decreased from 11.5 +/- 5.1 mmHg to 4.9 +/- 4.1 mmHg, mean cardiac output rose from 3.9 +/- 1.1 L/minute to 4.4 +/- 1.4 L/minute and mean calculated mitral valve area increased from 1.0 +/- 0.3 cm2 to 2.1 +/- 0.9 cm2. Ten patients developed clinically significant mitral incompetence requiring surgical mitral valve replacement. There were two transient cerebral embolic events. Small atrial septal defects were detected echocardiographically in 42 patients, but none has been a clinical problem. There were no early deaths; there were 11 late deaths, four of which were non-cardiac. Twenty patients have had repeat PTMV for re stenosis, four to 67 months after the first. CONCLUSIONS: PTMV provides significant haemodynamic and clinical improvement with low risk and should be considered the treatment of choice in patients with mitral stenosis. PMID- 9972412 TI - Comorbidities and prediction of length of hospital stay. AB - BACKGROUND: Variability in length of stay (LOS) within Australian National Diagnosis Related Groups (AN-DRGs) reflects clinical heterogeneity in age, severity of illness, complications and comorbidities. AIM: To develop a clinically based score which measures patient morbidity and which will better predict LOS compared to existing methods. METHODS: ICD-9-CM codes of diseases and procedures were allocated to one of 23 body system categories to calculate the body burden of disease (BBD) score. Evaluation of BBD in predicting LOS was performed using multiple regression and analysis of variance with a data set of 34,079 cases from 75 AN-DRGs from three Victorian hospitals. RESULTS: Adding BBD and age improved prediction of LOS by 27.2% in AN-DRG version 1.0 and by 17.5% in AN-DRG version 3.1. When using average inlier LOS for AN-DRG, BBD and age improved prediction of LOS by 44.6% and by 14.8% in AN-DRG version 1.0 and version 3.1 respectively. Deaths were positively related to BBD. CONCLUSIONS: BBD is a simple quantitative measure of extent of disease that improves current methods in accounting for variability in LOS. PMID- 9972413 TI - Postprandial dyslipidaemia in a nutshell: food for thought. PMID- 9972414 TI - Queensland tick typhus. PMID- 9972415 TI - Trigeminal neuralgia: should MRI be done routinely? PMID- 9972416 TI - Successful resolution of severe graft versus host disease after liver transplantation correlating with disappearance of donor DNA from the peripheral blood. PMID- 9972417 TI - Chronic meningococcaemia. PMID- 9972418 TI - Infections associated with central venous catheterisation for plasmapheresis. PMID- 9972419 TI - Mibefradil (Posicor) induced sinus arrest. PMID- 9972420 TI - Intracoronary stenting for acute myocardial infarction (AMI) in a 24-year-old man using anabolic androgenic steroids. PMID- 9972421 TI - Plasma exchange therapy. PMID- 9972422 TI - An unusually rapid onset of hyponatraemia following paroxetine. PMID- 9972423 TI - Splenic vein thrombosis in a renal transplant recipient. PMID- 9972424 TI - Intramural duodenal haematoma following endoscopic biopsy in a bone marrow transplant patient. PMID- 9972425 TI - Saksenaea vasiformis breast abscess related to gardening injury. PMID- 9972426 TI - Another case of high gentamicin clearance and volume of distribution in a patient with high output ileostomy. PMID- 9972427 TI - Methylene tetrahydrofolate reductase mutation and stroke in a monozygotic twin. PMID- 9972428 TI - Acute onset of pulmonary necrotising arteritis in a dog with a left-to-right patent ductus arteriosus. PMID- 9972429 TI - An old, lame cat with reduced food intake and stiff neck. PMID- 9972430 TI - Comparative cell morphology in the peripheral blood film from exotic and native animals. AB - Haematological investigation is an important part of disease diagnosis. This is particularly so when investigating individual animal disease. It may also be important when investigating diseases in groups of animals, but the opportunity to perform necropsies to directly detect diseases processes often diminishes its usefulness. Haematological investigation is essentially similar for all species. The presence of nucleated erythrocytes and thrombocytes in nonmammals requires alteration of haemoglobin measurement and cell counting. In addition, it may cause some confusion in identification of cells in peripheral blood films. Examination of blood films is an important component of haematological investigation and provides useful information on erythroid, leukocytic and platelet/thrombocytic alterations. Interpretation of alterations is essentially similar for all species. However, cell identification can at times be difficult. There are five basic leukocytes in all species: neutrophil (mammals) or heterophil (nonmammals), eosinophil, basophil, lymphocyte and monocyte. In nonmammals it may be difficult at times to distinguish between heterophils and eosinophils. In addition, lymphocytes may be confused with thrombocytes. However, a common-sense approach to the examination of the peripheral blood film will minimise this confusion. PMID- 9972431 TI - A severity score for spontaneous canine acute pancreatitis. AB - OBJECTIVE: To derive a severity score for spontaneous canine acute pancreatitis applicable to general practice. DESIGN: Cohort study of canine pancreatitis cases. PROCEDURE: Cases (n = 68) of spontaneous canine acute pancreatitis presented to general practitioners were identified among accessions to Veterinary Pathology Services Brisbane. The primary veterinarian was surveyed by telephone to ascertain the outcome of each case. Scores were assigned for extent of hyperamylasaemia, hyperlipasaemia and number of organ systems other than the pancreas compromised. The probability of mortality with each score of each analyte was calculated. The strength of interaction between scores for each analyte and mortality rate was assessed by chi-square analysis where appropriate. Relationships between the organ system score, other physiological variables and likelihood of euthanasia were analysed. RESULTS: Scores derived mathematically from analysis of enzyme activities had poor abilities to predict mortality. The score based upon the number of organ systems compromised showed good ability to predict mortality and the interaction between the organ system score and mortality rate was significant by chi-square analysis (P < 0.01). Distribution of data within the amylase and lipase scores was not compatible with chi-square analysis. CONCLUSION: Assessment of severity of spontaneous canine acute pancreatitis using pancreatic enzyme activities is potentially inaccurate. The use of a severity score based upon organ system compromise was more accurate in determining the likelihood of mortality in spontaneous canine acute pancreatitis. This is compatible with the hypothesis that severe canine acute pancreatitis is a multiple organ failure syndrome. PMID- 9972432 TI - Effect of desmopressin on plasma factor VIII and von Willebrand factor concentrations in Greyhounds. AB - OBJECTIVE: To determine the effect of 1-Deamino-8-D-arginine vasopressin on plasma concentrations of von Willebrand factor and factor VIII in Greyhound blood donors, and to compare the response of 1-Deamino-8-D-arginine vasopressin injection on plasma concentrations of von Willebrand factor between groups with different resting plasma concentrations of von Willebrand factor. ANIMALS: Fifteen Greyhound blood donors were used. Dogs were grouped into three categories depending on their von Willebrand factor concentrations. PROCEDURE: Desmopressin was administered subcutaneously at 1 microgram/kg [corrected] to all dogs. Plasma von Willebrand factor and factor VIII concentrations were measured before and 10, 20, 30, 45, 60, 90 and 120 min after desmopressin injection. RESULTS: The von Willebrand factor and factor VIII concentrations in all dogs increased significantly and remained higher than base-line throughout the 2 h period. CONCLUSION: Desmopressin is useful in increasing von Willebrand factor concentrations in Greyhound blood donors, including those with low resting concentrations. PMID- 9972433 TI - Transmission studies of Hendra virus (equine morbillivirus) in fruit bats, horses and cats. AB - OBJECTIVE: To determine the infectivity and transmissibility of Hendra virus (HeV). DESIGN: A disease transmission study using fruit bats, horses and cats. PROCEDURE: Eight grey-headed fruit bats (Pteropus poliocephalus) were inoculated and housed in contact with three uninfected bats and two uninfected horses. In a second experiment, four horses were inoculated by subcutaneous injection and intranasal inoculation and housed in contact with three uninfected horses and six uninfected cats. In a third experiment, 12 cats were inoculated and housed in contact with three uninfected horses. Two surviving horses were inoculated at the conclusion of the third experiment: the first orally and the second by nasal swabbing. All animals were necropsied and examined by gross and microscopic pathological methods, immunoperoxidase to detect viral antigen in formalin-fixed tissues, virus isolation was attempted on tissues and SNT and ELISA methods were used to detect HeV-specific antibody. RESULTS: Clinical disease was not observed in the fruit bats, although six of eight inoculated bats developed antibody against HeV, and two of six developed vascular lesions which contained viral antigen. The in-contact bats and horses did not seroconvert. Three of four horses that were inoculated developed acute disease, but in-contact horses and cats were not infected. In the third experiment, one of three in-contact horses contracted disease. At the time of necropsy, high titres of HeV were detected in the kidneys of six acutely infected horses, in the urine of four horses and the mouth of two, but not in the nasal cavities or tracheas. CONCLUSIONS: Grey-headed fruit bats seroconvert and develop subclinical disease when inoculated with HeV. Horses can be infected by oronasal routes and can excrete HeV in urine and saliva. It is possible to transmit HeV from cats to horses. Transmission from P poliocephalus to horses could not be proven and neither could transmission from horses to horses or horses to cats. Under the experimental conditions of the study the virus is not highly contagious. PMID- 9972434 TI - Lymphoid neoplasia in the koala. AB - OBJECTIVE: Correlation of immunophenotype with history, anatomical and morphological features of lymphoid neoplasia in the koala. METHODS: Routine necropsies were performed on 51 koalas with suspected lymphoid neoplasia between 1986 and 1997 in New South Wales and Queensland. Immunophenotyping was by an immunoperoxidase method utilising species cross-reactive antibodies raised against human lymphocytes and an antibody raised against koala IgG. Cases were classified according to organs and tissues affected and the morphological features of neoplastic cells. RESULTS: Twenty-six (51%) of the cases were of the T cell immunophenotype, 12 (24%) were of B cell immunophenotype and 13 (25%) did not stain. The age and sex of koalas did not correlate with immunophenotype (P = 0.686 and P = 1.000, respectively). Thirty-two cases were leukaemic and 36 had multiple organ involvement, probably reflecting presentation of koalas at advanced stages of disease. Abdominal tissue involvement was most common (44 cases), followed by nodal (32), atypical (21) and cervicomediastinal (14). The T cell immunophenotype was over-represented among the leukaemic cases (P = 0.013). Generally, the T cell immunophenotype predominated except for many affected atypical tissues. Neoplastic cells were mostly of medium nuclear size with round to oval nuclei. No correlations were found for cell morphology, mitotic index and immunophenotype. CONCLUSION: The prognostic value of an immunophenotypic, anatomical and morphological basis for the classification of lymphoid neoplasia in the koala currently is limited by the need to detect these neoplasms at an early age, the requirement for freshly fixed tissues and the restricted range of available cross-reacting antibodies. PMID- 9972436 TI - AVA campaign "false, emotive". PMID- 9972435 TI - Measurement of creatine kinase MB in canine cardiac patients. PMID- 9972438 TI - The influence of traumatic brain injury on acute stress disorder and post traumatic stress disorder following motor vehicle accidents. AB - This study compared the acute stress disorder and post-traumatic stress disorder (PTSD) symptom profiles in motor vehicle accident survivors who sustained a mild traumatic brain injury (MTBI) or no TBI. Consecutive adult patients who sustained a MTBI (n = 79) and no TBI (n = 92) were assessed for acute stress disorder within 1 month of their trauma and reassessed for PTSD (MTBI: n = 63; non-TBI; n = 72) 6-months post-trauma. Comparable rates of acute stress disorder and PTSD were reported in MTBI and non-TBI patients. Intrusive memories and fear and helplessness in response to the trauma were reported less frequently by MTBI than non-TBI patients at the acute phase. Six-months post-trauma fewer MTBI patients than non-TBI reported fear and helplessness in response to the trauma. These findings suggest that, whereas impaired consciousness at the time of a trauma may reduce the frequency of traumatic memories in the initial month post-trauma, MTBI does not result in a different profile of longer-term PTSD. PMID- 9972437 TI - Attention and memory dysfunction after traumatic brain injury: cholinergic mechanisms, sensory gating, and a hypothesis for further investigation. AB - Traumatic brain injury (TBI) is a common occurrence, with a rate of nearly 400,000 new injuries per year. Cognitive and emotional disturbances may become persistent and disabling for many injured persons, and frequently involve symptomatic impairment in attention and memory. Impairments in attention and memory have been well characterized in TBI, and are likely related to disruption of cholinergic functioning in the hippocampus. Additionally, disturbances in this neurotransmitter system may also account for disturbances in sensory gating and discriminative attention in this population. The electroencephalographic P50 waveform of the evoked response to paired auditory stimuli may provide a physiologic market of impaired sensory gating among TBI survivors. The first application of this recording assessment to the TBI population is reported. Preliminary findings in three cases are presented, and the interpretation of impaired sensory gating in this population is discussed. Given the impact of TBI on cholinergic systems, the effects of cholinergic augmentation on attention and memory impairment, and the availability of an electrophysiologic marker of cholinergic dysfunction responsive to cholinergic agents, a testable cholinergic hypothesis for investigation and treatment of these patients is proposed. PMID- 9972439 TI - Problems of patients with chronic aphasia: different perspectives of husbands and wives? AB - During the early phase following stroke, patients with aphasia and their families are totally involved in the rehabilitation programme, but later, in the chronic phase, after discharge, the family generally has no support and many problems may arise or become more acute and provoke disturbances in this system. The patients with aphasia and their spouses may feel the situation differently according to their own characteristics, including gender. The present study includes 55 spouses of patients with chronic aphasia and 37 controls (spouses of subjects without physical or cognitive impairments) who filled out a questionnaire concerning their respective spouses (European Brain Injury Questionnaire--EBIQ) and some aspects about themselves. It was concluded, from the opinions expressed by the spouses of patients with chronic aphasia that they have problems in several domains not only related to communication or physical impairments. The opinions of husbands and wives of patients with aphasia, but not of the controls, were different, with more references to behaviour changes in women with aphasia. Spouses' responses also show important changes in their own lives. These results stress the importance of adequate attention to the long-term psychosocial problems of patients and relatives. PMID- 9972440 TI - Does the requirement of a craniotomy predict outcome? A preliminary investigation. AB - The literature has been replete with reports that persons who require craniotomy for treatment of their traumatic brain injury have a far worse outcome. The majority of these reports have utilized the rather global Glasgow Outcome Scale as a determinant of outcome. This paper sought to evaluate the effect of craniotomy on outcome as measured by the DRS. Data was collected on 341 persons (mean age 37.7 years) with traumatic brain injury treated at the Level I trauma centre, who required inpatient rehabilitation. Surgical interventions were classified as 'no surgery', 'one cranial surgery', or 'two or more cranial surgeries'. Initial GCS scores revealed 44 persons at GCS 3-5, 102 persons at GCS 6-8, 83 persons at GCS 9-12 and 112 persons at GCS 13-15. The DRS was administered to each person at discharge from in-patient rehabilitation. Mean DRS scores were 7.07 for GCS 3-5, 6.03 for GCS 6-8, 6.53 for GCS 9-12, 5.57 for GCS 13-15 groups. A factorial ANOVA revealed an interaction between initial GCS and surgical status. Univariate ANOVA's demonstrated significant differences in the GCS 3-5 and GCS 13-15 groups, suggesting a relationship between need for surgical intervention and less favourable outcome among persons who required in-patient rehabilitation. However, no differences were demonstrated in the GCS 6-8 and GCS 9-12 groups. It appears that requiring surgical intervention is prognostic at only the extremes of the GCS categories and, thus, further investigation may reveal the limited role of need for surgical intervention injury in predicting outcome in persons with initial GCS 6-12. PMID- 9972441 TI - Progressive scoliosis in early, non-progressive CNS injuries: role of axial muscles. AB - Forty-three patients with progressive neurological deficits involving axial musculature, starting 3-6 years after non-progressive brain injuries insults are described. Losses of function followed period of several years of stable motor deficits. Subsequent losses were stereotypic, with loss of ambulation and scoliosis, followed by loss of word articulation, malalignment of the mandible and ultimately neurogenic impairment of swallowing. Physical therapy, serial castings and spinal instrumentation palliated specific musculoskeletal problems but did not alter the relentless loss of various functions. The balanced action of paired axial muscles (i.e. spine, proximal muscle groups of the lower extremities, oropharynx, mastication) is regulated by the brainstem with modulation by the cerebral hemispheres. The clinical evolution in these patients suggest that, in the absence of normal input from the cerebral hemispheres, some patients have a progressive loss of these brainstem mechanisms. The most resistant functions (last ones to be lost), seem to be the ones phylogenetically most relevant for survival, such as suction and swallowing. PMID- 9972442 TI - Circadian rhythm of cerebral perfusion pressure and intracranial pressure in head injury. AB - The aim of the study was to determine if Cerebral Perfusion Pressure (CPP) and Intracranial Pressure (ICP), in patients with head injury, has a circadian rhythm. CPP and ICP data of 13 patients were analysed using the Regressive and Iterative Cosinor methods. The Regressive Cosinor method did not detect a strong 24-hour rhythm. Therefore, the Iterative Cosinor method was used to seek rhythms with period not necessarily equal to 24 hours. Studying consecutive patient days by the Iterative cosinor method showed that rhythm is present but the rhythm period was often not 24 hours. A significant rhythm in the range of 20-30 hours was detected in eight patients for CPP (62%) and in six patients for ICP (46%). To validate the results real and surrogate time series were compared. The clinical implications of rhythmic data analysis are discussed. PMID- 9972443 TI - Biofeedback-assisted relaxation training with brain injured patients in acute stages of recovery. AB - There are few published accounts or empirical studies of biofeedback-assisted relaxation training with brain injured patients still in acute stages of recovery. Given the efficacy of biofeedback-assisted relaxation training with other medical populations, brain injured patients in acute stages of recovery with anxiety-based symptoms may also stand to gain some benefits from this form of treatment. It has yet to be determined, however, if severe cognitive impairment or disorientation contraindicate biofeedback treatment. The cases profiled here tentatively suggest that consideration of biofeedback-assisted relaxation training, even for severely cognitively impaired brain injured patients in acute stages of recovery, may be appropriate. Empirical investigations will be needed to determine selection criteria and contraindications for biofeedback treatment in the acute brain injury population. PMID- 9972444 TI - Selective serotonin reuptake inhibitor treatment of post-traumatic Kluver-Bucy syndrome. AB - Two cases of Kluver-Bucy syndrome following severe traumatic brain injury (TBI), are described during the period of recovery from acute TBI. These patients posed significant management problems, until successfully managed with selective serotonin reuptake inhibitors (SSRIs). These cases support the benefit of SSRIs in treating associated Kluver-Bucy syndrome. PMID- 9972445 TI - Effects of dopaminergic combination therapy for frontal lobe dysfunction in traumatic brain injury rehabilitation. AB - Traumatic brain injury poses significant and diverse challenges to rehabilitation efforts. Neurobehavioural deficits represent a particularly difficult barrier to rehabilitative progress and societal reintegration. Early studies have identified dopaminergic drugs such as amantadine, bromocriptine and sinemet as potentially assistive in countering these deficits. To date, side effect profiles have been relatively benign, noted most frequently in small-scale case trials. The case of a 40-year-old patient with bilateral frontal traumatic brain injuries, and previous arteriovenous malformation (AVM) bleed with significant ataxia, dysarthria and neurobehavioural deficits is presented. This long range study demonstrates, through multiple varied dosing schedules, a trade off between the benefits and side effects of dopaminergic therapy, with implications for a larger brain injury population. PMID- 9972446 TI - Forms and functions of cytochrome P450. PMID- 9972447 TI - The great diversity of reactions catalyzed by cytochromes P450. PMID- 9972448 TI - Metazoan cytochrome P450 evolution. AB - There are 37 cytochrome P450 families currently identified in animals. The concept of higher order groupings of P450 families called P450 CLANS is introduced. The mammalian CYP3 and CYP5 families belong to the same clan as insect CYP6 and CYP9. All mitochondrial P450s seem to belong to the same clan. Lack of mitochondrial P450s in C. elegans suggests that mitochondrial P450s probably arose from the mistargeting of a microsomal P450 after the coelomates diverged from acoelomates and pseudocoelomates. Different taxonomic groups appear to have recruited different ancestral P450s for expansion as they evolved, since each major taxon seems to have one large cluster of P450s. In insects, this cluster derives from the ancestor to the CYP4 family. Vertebrates and C. elegans may have used the same ancestor independently to generate the CYP1, 2, 17, and 21 families in vertebrates and a large distinctive clan with 45 genes in C. elegans. PMID- 9972449 TI - The aryl hydrocarbon receptor: a comparative perspective. AB - The aryl hydrocarbon receptor (Ah receptor or AHR) is a ligand-activated transcription factor involved in the regulation of several genes, including those for xenobiotic-metabolizing enzymes such as cytochrome P450 1A and 1B forms. Ligands for the AHR include a variety of aromatic hydrocarbons, including the chlorinated dioxins and related halogenated aromatic hydrocarbons whose toxicity occurs through activation of the AHR. The AHR and its dimerization partner ARNT are members of the emerging bHLH-PAS family of transcriptional regulatory proteins. In this review, our current understanding of the AHR signal transduction pathway in non-mammalian and other non-traditional species is summarized, with an emphasis on similarities and differences in comparison to the AHR pathway in rodents and humans. Evidence and prospects for the presence of a functional AHR in early vertebrates and invertebrates are also examined. An overview of the bHLH-PAS family is presented in relation to the diversity of bHLH PAS proteins and the functional and evolutionary relationships of the AHR and ARNT to the other members of this family. Finally, some of the most promising directions for future research on the comparative biochemistry and molecular biology of the AHR and ARNT are discussed. PMID- 9972451 TI - Avian forms of cytochrome P450. AB - Despite the importance of avian P450 forms in modulation of the toxicity of pesticides and other environmental chemicals, relatively little work has been done upon them, and very few forms have been fully characterised. An avian form that appears to belong to family 1A is readily inducible by planar molecules (e.g. coplanar PCB's, PCDD and certain PAHs) and has been the basis of a biomarker assay used in field studies. Although it is recognised by antibodies for mammalian P450 1A1, it evidently differs from the mammalian forms of the enzyme in catalytic properties. Phenobarbitone induces two forms of P450 in the domestic fowl (2H1 and 2H2) which have been purified, and these resemble P450 2B1 and P450 2B2 of the rat respectively. Two further phenobarbitone inducible forms, PB-A and PB-B have been partially purified. Also there is an acetone inducible form that resembles rodent P450 2E. In field studies evidence has been produced for the induction of P450s recognised by antibodies to mammalian forms of P450 1A1 and P450 2B in avian liver (adults and embryos), in response to environmental levels of PCBs. Fungicides which act as ergosterol biosynthesis inhibitors (EBI fungicides) such as prochloraz and propiconazole potentiate the toxicity of certain phosphorothionates to birds. PMID- 9972450 TI - Cytochrome P450 induction in feral Cricetid rodents: a review of field and laboratory investigations. AB - The constitutive and inducible hepatic cytochromes P450 of various feral Cricetid rodents (family Cricetidae, comprising various New World rats and mice, hamsters, gerbils and voles), have been examined in a relatively limited number of field and laboratory investigations. These studies, reviewed herein, have employed substrates and immunochemical reagents that are diagnostic for individual P450 subfamilies of Rattus norvegicus (the common laboratory species derived from the Norway rat, a member of the family Muridae). The results have demonstrated that the feral rodents display hepatic responses to prototypic CYP1A inducers (3 methylcholanthrene, beta-naphthoflavone) similar to those displayed by R. norvegicus and Mus musculus (the common laboratory species derived from the house mouse, another member of the family Muridae). At least one study has demonstrated the induction, by ethanol, of a protein immunochemically similar to CYP2E1 in a Cricetid rodent. In Cricetid rodents, phenobarbital-type inducers cause the induction of a hepatic protein immunologically similar to that primarily induced (CYP2B) in R. norvegicus and M. musculus. The proteins induced in the Cricetid rodents, however, exhibit striking differences in substrate specificity, compared to the proteins induced in R. norvegicus. These results indicate that the previously described differences between the P450 induction responses exhibited by the commonly utilized laboratory species R. norvegicus and M. musculus (family Muridae) and the Syrian hamster and gerbil (family Cricetidae) are observed as a generality for members of the Cricetid family of rodents. PMID- 9972452 TI - Cytochrome P450 enzymes in chickens: characteristics and induction by xenobiotics. PMID- 9972453 TI - The microsomal mixed function oxidase system of amphibians and reptiles: components, activities and induction. AB - This article reviews current research in amphibian and reptilian cytochromes P450, important to the overall understanding of xenobiotic metabolism in the ecosystem and the evolution of P450s. Amphibians and reptilians contain the normal mixed function oxidase system (MFO). In general the MFO content and activities are less than those found in mammals, but only a few of the known activities have been examined in these vertebrate classes. Research to date has focused on two families of cytochromes P450, CYP1 and 2. The isoforms examined catalyze the classic activities but there have been notable absences. The total number of isoforms present and the breadth of substrates metabolized are yet unknown. Induction by foreign compounds (xenobiotics) is lengthier and yields lower levels of induced activity than is typically found in mammals. When these animals are pretreated with 3-methylcholanthrene (3MC) and beta-naphthaflavone (BNF), which are known to induce the same isoform in mammals, multiple isoforms are induced with different activities. Phenobarbital-pretreatment in turtles and alligators induces cytochromes P450 and suggestive data indicates induction in the lizard Agama lizard and the newt Pleurodeles waltl. In amphibians and reptiles a CYP2B protein does appear to be present along with constitutive activities associated with the 2 family of cytochromes P450. The markedly different response to classic inducers combined with lower or absent activities alters the view of how amphibians and reptilians respond to xenobiotic challenges. PMID- 9972454 TI - Rainbow trout cytochrome P450s: purification, molecular aspects, metabolic activity, induction and role in environmental monitoring. AB - Cytochromes P450 (P450s or CYPs) constitute a superfamily of heme-thiolate proteins that play important roles in oxidative metabolism of endogenous and exogenous compounds. This review provides some limited history but addresses mainly the research progress on the cytochrome P450s in rainbow trout (Oncorhynchus mykiss), their purification, structures at the primary level, role in metabolism, responses to chemicals and environmental pollutants, application to biomonitoring and the effect of various factors on their expression or activities. Information obtained to date suggests that the rainbow trout P450 systems are as complex as those seen in mammals. Fourteen P450s have been purified from liver or trunk kidney to relatively high specific content. cDNAs belonging to seven different P450 families have been documented from trout liver, kidney and ovary. Two CYP1A genes, nine cDNAs containing open reading frames, and a cDNA fragment were entered into GenBank. Among them, CYP2K1, CYP2K3, CYP2K4, CYP2M1, CYP3A27 and CYP4T1 are the most recently described forms. CYP2K1, CYP2M1 and CYP4T1 represent newly identified P450 subfamilies first described in the rainbow trout. In many cases, the cloned rainbow trout P450s have subsequently been expressed in heterologous expressions systems such as COS-7 cells, yeast and baculovirus infected insect cells. Some of the overexpressed P450 isoforms have been partially characterized. Potential future research directions are discussed. PMID- 9972455 TI - Cytochrome P450 monooxygenase system in echinoderms. AB - The results of a limited number of studies on echinoderms provide evidence for the presence of a cytochrome P450 monooxygenase system in representatives of three classes of the phylum Echinodermata: the asteroids (sea stars), holothuroids (sea cucumbers) and echinoids (sea urchins). The monooxygenase system has been demonstrated to be involved in the metabolism of xenobiotic compounds, but is assumed to have its primary function in the metabolism of endogenous substrates, such as steroids. Available data on P450 cofactor requirement, P450-dependent metabolism of benzo[a]pyrene, studies with classical inhibitors of P450, specificity of P450 induction by planar compounds, and the changes in the benzo[a]pyrene metabolite profile in induced animals suggest similarities with the MO system present in vertebrates. However, the relatively high capacity of the monooxygenase system in sea stars to catalyse reactions with organic hydroperoxide as donor for activated oxygen, and the low induceability during exposure to xenobiotics indicate also important differences between the echinoderm cytochrome P450 monooxygenase system and that of vertebrates. Some evidence was found for the existence of different forms of cytochrome P450 in sea stars. Catalytic functions of the cytochrome P450 monooxygenase system of sea stars in the metabolism of steroids may be suppressed as a result of the induction of cytochrome P450 by xenobiotics. PMID- 9972456 TI - Insect cytochromes P450: diversity, insecticide resistance and tolerance to plant toxins. AB - In the last decade, studies of individual insect P450s have blossomed. This new information has furthered our understanding of P450 diversity, insecticide resistance and tolerance to plant toxins. Insect P450s can be adult specific, larval specific or life stage independent. Similarly, insect P450s vary as to the tissues where they are expressed and in their response to inducers. Insect P450s can now be rapidly sequenced using degenerate PCR primers. Given the huge diversity represented by the Class Insecta, this technique will provide vast amounts of new information about insect P450s and the evolution of the P450 gene superfamily. CYP6D1 is responsible for monooxygenase-mediated resistance to pyrethroid insecticides in the house fly. CYP6D1 is ubiquitously expressed in adults with 10-fold higher levels found in the resistant strain compared to susceptible strains. CYP6D1 is on autosome 1 in house fly. The high level of expression found in the resistant strain is due to genes on autosomes 1 and 2. Whether or not the different CYP6D1 alleles found in resistant and susceptible strains have any role in resistance remains to be elucidated. The CYP6B gene subfamily is involved in the metabolism of host plant toxins (i.e. furanocoumarins). CYP6B gene transcripts in two Papilio (swallowtail) species have been shown to be induced by host plant toxins and in turn to metabolize these toxins. CYP6B P450s play a critical role in allowing Papilio to adapt to furanocoumarin-containing host plants. Similarities in structural and promoter regions of the CYP6B genes suggest that they are derived from a common ancestral gene. Although the P450 monooxygenases of insects are important for the metabolism of hormones and phermones, no individual P450 has yet been shown to metabolize an endogenous compound. Advances in this area are critical because they will provide important new information about insect physiology, biochemistry and development. PMID- 9972457 TI - Cytochromes P450 in crustacea. AB - Since the last review of this topic, further insight has been gained into the presence and functions of cytochrome P450 proteins in the hepatopancreas and other organs of aquatic crustacean species, although progress has been slow relative to the advances in other species. Recent studies with several lobster, shrimp, crab and crayfish species suggest that cytochromes P450 in the 2 and 3 families are the most abundant forms in hepatopancreas microsomes. Substrates normally metabolized by CYP2 and CYP3 family members are monooxygenated more rapidly by crustacea than substrates normally metabolized by CYP1 family enzymes, e.g. erythromycin, testosterone and aminopyrine are much more rapidly monooxygenated than ethoxyresorufin. Some progress has been made in cloning and sequencing crustacean P450 forms. CYP2L1 and CYP2L2 cDNA sequences have been cloned from spiny lobster hepatopancreas libraries, and there was evidence for at least two more cytochromes P450 in spiny lobster hepatopancreas. An area of continued interest, but of no consensus or general findings, relates to the presence and inducibility of CYP1 family members in crustacea. Some studies indicate weak induction of total cytochrome P450 and increased turnover of substrates normally associated with CYP1, while others show no effect of the classic inducers that act at the Ah receptor in vertebrates. A few studies of the roles of cytochromes P450 in the biosynthesis and degradation of steroids, including ecdysteroids, have been published. Further studies are needed to understand the regulation and normal function of the crustacean cytochromes P450. PMID- 9972458 TI - Annelid cytochrome P-450. AB - Both classes of Annelida--Polychaeta and Clitellata--have been shown to contain cytochrome P-450. The metabolism of a number of aromatic hydrocarbons, drugs and pesticides by annelids required oxygen and NADPH, and was inhibited by a variety of cytochrome P-450 inhibitors. A number of types I and II substrates bound to the cytochrome P-450 in polychaete microsomes to give typical types I and II binding spectra. These results suggest that xenobiotics in annelids are metabolized by a typical cytochrome P-450 mixed function oxygenase. In addition to xenobiotics, annelid cytochrome P-450 systems are likely to function in the biosynthesis and metabolism of sterols and hormones found in annelids, such as cholesterol, ecdysteroids and eicosanoids. The primary source of cytochrome P-450 isolated to date from annelids has been intestinal microsomes. Cytochrome P-450 concentrations in these microsomes varied from 8 to 580 pmol mg-1 of protein. The only cytochrome P-450s purified from annelids were the three isomers isolated from microsomes of the oligochaete, Lumbricus terrestris, whose molecular masses were 48,000, 51,000 and 53,000 Da. Work on the induction of cytochrome P-450 in polychaetes by exposure to polycyclic aromatic hydrocarbons or polychlorinated biphenyls has given conflicting results, since some groups found induction after such exposure, but others found no induction. One possible explanation may be exposure to natural soil and sediments inducers, e.g. plant alkaloids, during feeding. Since gene and protein sequences have yet to be carried out on the cytochrome P-450 of any annelid, the relationship of annelid cytochrome P-450s to the 74 families of P-450 so far found, remains to be carried out. PMID- 9972459 TI - Cytochrome P450 in parasitic protozoa and helminths. AB - Cytochrome P450 has been demonstrated in flagellate and sporozoan Protozoa. In Plasmodium there is a correlation between chloroquine resistance and cytochrome P450 mono-oxygenase activity, but there is no evidence that the malarial parasite metabolises chloroquine by an oxidative mechanism. There is no evidence for cytochrome P450 in adult helminths (nematodes and platyhelminths) based on P450 content and mono-oxygenase activity with classical substrates, although low activities may be present in free-living larval stages. PMID- 9972460 TI - Occurrence of flavin-containing monooxygenases in non-mammalian eukaryotic organisms. AB - Flavin-containing monooxygenases (FMOs) have been identified in various organisms from bacteria to humans. However, because of the importance of these enzymes in the biotransformation of xenobiotics, the majority of studies have focused almost entirely upon the mammalian forms of the enzyme. Consequently, this review is an attempt to document the occurrence of FMO expression (mRNA, proteins, activities) in non-mammalian species in an attempt to provide insight about its putative physiological and toxicological roles. Activity indicative of FMO has been observed in numerous invertebrate species but corresponding proteins or transcripts have not been identified. There is a significant gap of information pertaining to insects, echinoderms, avian, reptilian and amphibian species. Significant homology of structure and function is observed in lower vertebrates. Evidence is provided primarily from studies with piscine forms of the enzyme suggesting a possible osmoregulatory role of FMOs, especially in euryhaline species of fish. PMID- 9972461 TI - Dose-response relationships for cytochrome P450 induction by phenobarbital in the cotton rat (Sigmodon hispidus). AB - The induction of a hepatic pleiotropic response, including increase in liver/body weight ratio, induction of hepatic CYP2B and CYP3A protein and catalytic activity, and hepatic microsomal epoxide hydration activity, was investigated in male cotton rats (Sigmodon hispidus) administered graded dietary concentrations (0-1500 ppm) of phenobarbital (PB) for 14 days. A dose-dependent induction of each endpoint was observed, although plateaus in the various dose-response curves were not obtained, and ED50 values (PB concentrations associated with half maximal responses) for the various endpoints were not able to be calculated. A maximal 1.31-fold increase, compared to the control value, in live/body weight ratio was observed, while microsomal epoxide hydration activity was increased as much as 3.6-fold by PB administration. Pentoxy- and benzyloxyresorufin O dealkylation and testosterone 16 beta-hydroxylation activities (considered to be relatively selective for CYP2B in the Norway rat (Rattus norvegicus)), were induced maximally less than five-fold. Testosterone 6 beta-hydroxylation (considered to be relatively selective for CYP3A in R. norvegicus) was induced maximally less than two-fold. Maximal induction of 7-ethoxy-4-trifluoromethyl coumarin O-deethylation was 18-fold, compared to the control rate. Western blotting studies indicated that hepatic microsomal proteins immunoreactive with polyclonal antisera to R. norvegicus CYP2B1 or CYP3A1 were induced, in a dose responsive manner, by PB in the cotton rats. These results indicate that the cotton rat responds to PB treatment with a coordinate pleiotropic response similar to that displayed by R. norvegicus, although the substrate specificity of the induced proteins appears to differ between the two rodent species. PMID- 9972462 TI - Multiplicity and tissue specific expression of camel cytochrome P450(s). AB - The presence of multiple forms of the cytochrome P450 was demonstrated enzymatically in camel tissues using a variety of isoenzyme specific substrates and immunochemically using isoenzyme specific antibodies. The maximum catalytic activity using xenobiotics as substrate was observed in the liver followed by the kidney. However, lauric acid hydroxylation was found to be higher in the kidney than in any other tissues. Camel liver microsomal monooxygenase activity using aniline, aminopyrene, ethoxycoumarin, ethoxyresorufin and benzo(a)pyrene as substrates was comparable with those of rat and human livers. The activity of the enzymes in extrahepatic tissues of the camel was comparable with those of the rat extrahepatic tissues. The maximum expression of P450 protein was seen in the camel liver and kidney while the brain and intestine exhibited relatively low levels of expression. P450 expression in camel tissues appeared to be higher than in rat tissues. Immunohistochemical staining of P450 in the camel liver, kidney and brain confirmed the higher expression of P450 enzyme proteins in the liver and kidney as compared to other extrahepatic tissues. The maximum expression of P450 in the liver was observed in hepatocytes around the central vein and in the kidney it was observed in the proximal tubules. These results demonstrate that the multiple forms of P450s are differentially expressed in camel tissues and that the relative levels of expression are comparable with those of rat and human tissues. These observations may be important in understanding the differential susceptibility of camel tissues to the toxic/therapeutic effects of xenobiotics/drugs and environmental pollution. PMID- 9972463 TI - EROD induction by environmental contaminants in avian embryo livers. AB - The CYP1A (EROD)-inducing potencies of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), 3,3',4,4',5-pentachlorobiphenyl (PCB126) and benzo(k)fluoranthene (B(k)F) were studied in avian embryo livers. TCDD and PCB126 proved to be much more potent as inducers in the chicken than in the other species examined. This finding is consistent with a considerably higher sensitivity of the chicken compared with a number of other avian species to the embryotoxic effects of these compounds. Furthermore, the relative potencies of the tested Ah receptor agonists as CYP1A inducers differed substantially between species. B(k)F and PCB126 showed similar induction potencies in domestic duck embryos, whereas PCB126 is much more potent than B(k)F in the chicken. Also, the potency of PCB126, relative to that of TCDD, was much lower in quail embryo liver in vitro than in chicken embryo liver. Thus, there are large interspecific differences in birds in the sensitivity to CYP1A inducers and furthermore, the relative potencies of these compounds may differ substantially between species. PMID- 9972464 TI - Cytochrome P450 enzymes in the kidney of the bobwhite quail (Colinus virginianus): induction and inhibition by ergosterol biosynthesis inhibiting fungicides. AB - Metabolism of testosterone and the alkoxyresorufins was examined in kidney microsomes from male Bobwhite quail (Colinus virginianus) and was compared with that in kidney microsomes prepared from the male rat. In addition, cross reactivity studies were conducted with a number of antibodies prepared against cytochrome P450 (CYP) enzymes purified from rat and trout liver. The effects of treatment with the fungicides: propiconazole, vinclozolin, clotrimazole and ketoconazole were examined. While kidney microsomes from both quail and rat catalyzed testosterone metabolism at multiple positions, the pattern of hydroxylated metabolites differed. Treatment with vinclozolin resulted in significant induction of testosterone 2 beta- and 15 beta-hydroxylase activity in quail kidney accompanied by increases in expression of P450 enzymes cross reactive with antibodies raised against a CYP 3A-like protein in teleost fish. In contrast, ketoconazole treatment resulted in inhibition of testosterone hydroxylation at positions 15 beta- and 6 alpha-. Propiconazole and vinclozolin significantly induced a CYP 1A1 cross-reactive P450 enzyme in quail kidney 2-3 fold unaccompanied by significant increases in alkoxyresorufin O-dealkylase activity. These activities were significantly inhibited by ketoconazole treatment. Quail kidney microsomes also expressed high levels of a CYP 4A1 cross reactive apoprotein which was inducible 3-4-fold by ketoconazole. Thus, quail kidney possesses cytochrome P450 enzymes related to forms found in mammalian gene families 1, 3 and 4. Fungicide treatment results in mixed patterns of induction and inhibition of kidney P450 enzymes different from those previously reported in quail liver. PMID- 9972465 TI - Molecular cloning of CYP1A from the estuarine fish Fundulus heteroclitus and phylogenetic analysis of CYP1 genes: update with new sequences. AB - Since we published a phylogenetic analysis of the CYP1A subfamily in 1995, several additional full-length sequences have been reported, including three members of an entirely new subfamily, CYP1B. Two avian sequences were recently published, so that CYP1A sequence data are now available from three of the five major vertebrate lineages. The two new branches that have been added to the CYP1 family tree significantly add to our understanding of P450 evolution. The inclusion of the CYP1Bs to the phylogenetic analysis allows us to root inferred trees. Addition of the avian CYP1As indicates that the CYP1A1/CYP1A2 duplication present in the mammalian lineage may have occurred after the divergence of birds and mammals. The number of fish species from which full-length coding regions of CYP1A genes have been sequenced has increased from four (trout, plaice, toadfish, and scup) to nine. These include CYP1A sequences from tomcod, butterflyfish, sea bream, sea bass, and the full-length sequence of CYP1A from the killifish Fundulus heteroclitus that is reported here. Phylogenetic analyses incorporating the new fish CYP1A sequences support our original conclusion that the fish CYP1As are monophyletic and indicate that the genes are evolving at very different rates in different species. PMID- 9972466 TI - Molecular cloning of a CYP1A cDNA from the teleost fish Dicentrarchus labrax. AB - A cDNA encoding for cytochrome P450 1A has been cloned in the marine teleost fish Dicentrarchus labrax. This fish, common in the Mediterranean, was chosen since it is considered a good sentinel species. Moreover, biomarkers of exposure to organic contaminants (such as EROD) are often measured in this species and make it possible to evaluate the quality of waters. For cloning purposes, RNAs were extracted from the liver of benzo[a]pyrene (BaP)-treated animals and used as template in degenerate RT-PCR. The cDNA product was cloned and used for the design of highly stringent primers that were utilized in Rapid Amplification of cDNA Ends (RACE) PCR. The cloned cDNA hybridizes with a 2.7 kb mRNA which is induced by treatment of the fish with BaP, a classical CYP1A inducer. The closest sequences found in data banks belong to fish CYP1A. PMID- 9972467 TI - Preparation of highly purified cytochrome P4501A1 from leaping mullet (Liza saliens) liver microsomes and its biocatalytic, molecular and immunochemical properties. AB - Cytochrome P4501A1 was purified to electrophoretic homogeneity from the liver microsomes of feral fish leaping mullet (Liza saliens) collected in Izmir Bay, Aegean coast of Turkey. Purification of cytochrome P4501A1 involved anion exchange chromatography of Emulgen 913-cholate solubilized microsomes on first- and second-DEAE-cellulose columns, hydrophobic interaction chromatographies of the partially purified cytochrome P4501A1 on Porapak Q and phenyl-Sepharose CL-4B and further purification on adsorption chromatography on the hydroxylapatite column. Finally, it is further concentrated and purified on the third DEAE cellulose column. The purified cytochrome P4501A1 was characterized with respect to spectral, electrophoretic, immunochemical and biocatalytic properties. Cytochrome P4501A1, purified 32-fold with a specific content of 15-17 nmoles P450 (mg protein)-1, produced a single band on SDS-polyacrylamide gel electrophoresis having monomer molecular weight of 58,000 +/- 500. Absolute absorption spectrum of the purified cytochrome P4501A1 fractions showed maximal absorption at 417.5 nm and CO-difference spectrum of dithionite-reduced cytochrome P4501A1 gave a peak at 448 nm. Purified P4501A1 was found to be active in the O-deethylation of 7-ethoxyresorufin in the reconstituted system containing purified fish liver cytochrome P450 reductase and synthetic lipid. However, it was unable to catalyze the oxidation of the other monooxygenase substrates such as benzphetamine and aniline known to be specific for the other isozymes. Purified L. saliens liver microsomal cytochrome P4501A1 showed strong cross-reactivity with the antibodies directed against the cytochrome P4501A1 homologues purified from other teleost species such as rainbow trout and scup. Spectral, electrophoretic, immunochemical and biocatalytic properties of the purified cytochrome P4501A1 strongly suggested that it is the CYP1A1 in the L. saliens liver. PMID- 9972468 TI - Cytochrome P450-dependent metabolic pathways and glucuronidation in trout liver slices. AB - We investigated the capacity of trout precision-cut liver slices to metabolize xenobiotics and steroids. As a first approach, liver slices were compared with freshly isolated trout hepatocytes, using 7-ethoxycoumarin (7-EC) and testosterone as substrates. Trout liver slices and freshly isolated hepatocytes had a similar capacity for conducting cytochrome P450-dependent metabolism, as indicated by the rate of oxidative metabolism of 7-EC and testosterone, and by the metabolic profile of these substrates. A lower rate of glucuronidation in slices compared with hepatocytes was observed with testosterone (50 microM), whereas the opposite situation occurred with 7-EC used at higher concentration (100 microM). In a second step, we investigated the effect of beta-naphthoflavone on 7-EC and testosterone biotransformation, using slices maintained in culture for 24 h, with or without the inducer added. The results were compared with the metabolic rates of these substrates incubated with liver slices originating from trout pretreated in vivo with beta-naphthoflavone. Cytochrome P450-mediated rates of 7-EC dealkylation and testosterone hydroxylation decreased to 38 and 55% of the control value, respectively, when incubations were performed in 24-h cultured slices instead of freshly cut slices. Exposure of the slices to 50 microM beta naphthoflavone resulted in about 3 times higher deethylation rate of 7-EC. A similar value was obtained when treatment occurred in vivo. As demonstrated in rat by several authors, liver slices seem a useful and simple tool for studying the metabolic pathways of xenobiotics and steroids and for the assessment of inducers of the CYP1A1 family. PMID- 9972469 TI - Effects of triphenyltin and other organotins on hepatic monooxygenase system in fish. AB - The interaction of the organotin fungicide triphenyltin chloride (TPT) with fish microsomal monooxygenase systems has been studied in vitro and in vivo in the marine fish scup (Stenotomus chrysops). In vitro incubation of fish liver microsomes with TPT resulted in the conversion of about 40% of the native total spectral P450 to P420. In addition, a strong concentration-related inhibition of ethoxyresorufin O-deethylase (EROD) activity was observed, with a complete loss at 1.0 mM TPT. Pentoxyresorufin-O-dealkylase (PROD) activity was inhibited only at the highest concentration tested. This suggests either some specificity for the EROD catalyst CYP1A1, or a loss of reductant NADPH cytochrome c reductase as the cause. Further in vitro incubations showed that NADPH, but not NADH, cytochrome c reductase was strongly inhibited at 100 microM TPT and higher. To further investigate this effect, fish were injected with single doses of 5, 25 and 50 microM TPT (1.9, 9.6 and 19.3 mg kg-1 TPT), and 24 and 48 h later, hepatic microsomes were analyzed for total P450 content, EROD activity, NAD(P)H cytochrome c reductase, and the content of three CYP forms. EROD activity tended to be decreased in TPT-treated scup, with the response being stronger after 48 than 24 h. No significant conversion of spectrally determined P450 to cytochrome P420 was found, and cytochrome b5 was not affected. However, both NAD(P)H cytochrome c reductases were significantly inhibited at all concentrations. Immunoblot analysis showed reduction of CYP1A1 content at all doses, being significant at 25 mM after 48 h, but no decrease in CYP3A-like protein, the dominant catalyst of testosterone 6 beta-hydroxylation, nor CYP2B-like protein, the major contributor to indicates significant effects of TPT at high concentrations on fish hepatic CYP1A1 protein, EROD activity and the reductases. TPT seems to act more specifically on CYP1A1 than on other CYP forms. These findings combined with those of our previous studies (Bruschweiler BJ, Wurgler FE, Fent K. Environ Toxicol Chem 1996;15:827-735; Fent K, Bucheli TD. Aquat Toxicol 1994;28:107-126; Fent K, Stegeman JJ. Aquat Toxicol 1991;20:159-168; Fent K, Stegeman JJ. Aquat Toxicol 1993;24:219-240) indicate a general degenerative effect of organotins on the fish microsomal monooxygenase system, although some differences are seen between the organotins, and between species. We conclude that these effects of organotins have consequences for use of CYP1A as a biomarker and endocrine disruption. PMID- 9972470 TI - Interaction of isosafrole, beta-naphthoflavone and other CYP1A inducers in liver of rainbow trout (Oncorhynchus mykiss) and eelpout (Zoarces viviparus). AB - The CYP1A enzyme in liver of rainbow trout (Oncorhynchus mykiss) and eelpout (Zoarces viviparus) was induced by intraperitoneal injections of isosafrole (ISF), beta-naphthoflavone (BNF), retene, 3,3',4,4'-tetrachlorobiphenyl (TCB), Clophen A50 and combinations of these compounds. The livers were sampled 5 days after injection and the microsomal fraction was used to measure the activity of CYP1A (as ethoxyresorufin-O-deethylase (EROD)) and the level of the enzyme (measured semiquantitatively as absorbance using enzyme-linked immunosorbant assay (ELISA)). Induction of CYP1A above the additive effect was observed when ISF was given together with BNF or retene. It was suggested that ISF may stabilize the enzyme or its mRNA or that ISF metabolites inhibit CYP1A processing of BNF and retene, thus increasing the effective doses of these compounds in fish liver. The results indicate a need for further studies of interactions between different CYP1A inducers in fish and a comparison of CYP1A response between different fish species. These results may have implications for the use of CYP1A induction in fish as a biomarker in aquatic systems, since a high EROD activity could be due not only to the presence of one potent inducer, but to synergistic effects of two or more inducers at low concentrations. PMID- 9972471 TI - Induction of lauric acid hydroxylase activity in catfish and bluegill by peroxisome proliferating agents. AB - In mammals, sensitivity to peroxisome proliferation by peroxisome proliferating agents (PPAs) appears to be correlated with inducibility of lauric acid hydroxylase activity. Bluegill and catfish have been shown to respond to PPAs by induction of lauric acid hydroxylase immunoreactive proteins (Haasch, 1996). In this investigation, induction of lauric acid hydroxylase activity was confirmed by HPLC and mass spectral analysis of specific hydroxylation products and possible species-specific differences in metabolism were investigated. Male bluegill, channel catfish and rat, were administered the model PPAs, clofibrate (200 mg kg-1, i.p.), ciprofibrate (100 mg kg-1, i.p.), or olive oil as vehicle control (both sexes of catfish), 48 h prior to hepatic, trunk kidney (catfish only) or kidney (rat) microsome preparation. In general, total metabolism of lauric acid was similar in all species, but female catfish metabolize lauric acid to a greater extent than males. Ciprofibrate treatment produced significant induction of omega- and omega-6 hydroxylation in male catfish kidney. In male bluegill liver, omega-, omega-4 and omega-5 hydroxylations were significantly induced by clofibrate treatment. The data indicate that induction of lauric acid hydroxylase cytochrome(s) P450 occurs in PPA-exposed fish which may be a consideration for environmentally-exposed responsive species. PMID- 9972472 TI - Immunochemical characterization of hepatic cytochrome P450 isozymes in the channel catfish: assessment of sexual, developmental and treatment-related effects. AB - The profiles of immunoreactive proteins recognized by antibodies raised against purified trout P-450 isoforms (CYP1A1, CYP2M1 and CYP2K1) were examined in channel catfish liver by Western blot analysis. Gender differences in basal expression of these isoforms, as well as responses to known inducers of mammalian isoforms (ethanol, beta-naphthoflavone and clofibric acid) and early life stage (3 and 6 months) profiles are described. Two similar protein bands were detected by Western blotting in mature untreated catfish with CYP2K1 and CYP2M1 antibodies. A third band is detected by anti-2K1 in fish treated with beta naphthoflavone; this band was verified as CYP1A, with about twice the level of expression in males versus females. No difference between sexes was seen in the expression of the 51-kDa CYP2-reactive bands; however, a significant difference (female > male) was seen in the lower molecular weight CYP2 band (47-kDa). Ethanol treatment caused a dose-dependent decrease in the 47-kDa CYP2-reactive isoforms but no change in the 51-kDa band. Clofibric acid treatment caused an increase in both the 51-kDa CYP2 protein as well as in liver somatic index. Age dependent changes in isoform expression were also detected in CYP2-reactive forms, with a novel protein (53-kDa) detected in 3-month-old fish. The results from this study provide insight into the regulation of constitutive catfish CYP isoforms and prepares a foundation for further examination of the biotransformation capabilities of an important aquatic species. PMID- 9972473 TI - Induction of cytochrome P450 activities in Drosophila melanogaster strains susceptible or resistant to insecticides. AB - We analysed Drosophila melanogaster cytochrome P450s (P450) through the measurements of four enzymatic activities: ethoxycoumarin-O-deethylase, ethoxyresorufin-O-deethylase, lauric acid hydroxylation, and testosterone hydroxylation. We did these measurements in two Drosophila strains: one is susceptible to insecticides (Cantons) and the other is resistant to insecticides by enhanced P450 activities (RDDTR). In addition, we also treated the flies with eight chemicals (beta-naphtoflavone, benzo-alpha-pyrene, 3-methylcholanthrene, phenobarbital, aminopyrine, rifampicin, prochloraz, and clofibrate) known to induces genes from the families CYP1, CYP2, CYP3, CYP4, and CYP6. Metabolisation of all the substrates by P450 from flies microsomes was observed. The chemicals had different effects on these activities, ranging from induction to inhibition. The effects of these chemicals varied with the strains as most of them were ineffective on the RDDTR strain. The results showed that P450-dependent activities are numerous in Drosophila. Regulation features of these activities are complex. The availability of mutant strains as RDDTR should allow fundamental studies of P450 in insects. PMID- 9972474 TI - Mixed function oxidase induction in Carcinus aestuarii. Field and experimental studies for the evaluation of toxicological risk due to Mediterranean contaminants. AB - The aim of this study was to test and validate the use of mixed function oxidase (MFO) induction, in the crab Carcinus aestuarii, under experimental and field studies, for the evaluation of toxicological risk due to the main contaminants in the Mediterranean. Two different experiments were performed in the laboratory in order to identify the most suitable tissues for MFO studies in this species and the most suitable and sensitive MFO responses for evaluating chemical stress due to lipophilic contaminants. In order to validate this methodology in the field, two studies were carried out in two polluted Mediterranean lagoons: a transplant experiment in Orbetello Lagoon and an in situ experiment in Venice Lagoon. The following MFO responses were investigated in hepatopancreas and gills of the crabs: ethoxyresorufin-O-deethylase (EROD) and benzo(a)pyrene hydroxylase (BPH) activities and reductase enzyme activities. The main results can be summarised as follows: midgut-gland and gills were confirmed to be useful for MFO tests; BPH activity in hepatopancreas was the most suitable and sensitive MFO response for evaluating chemical stress due to Mediterranean contaminants in laboratory and field studies; in the Orbetello Lagoon experiment, a statistically significant difference was found between sites subject to different human impact. PMID- 9972475 TI - Cytochrome P450 system in the hepatopancreas of the red swamp crayfish Procambarus clarkii: a field study. AB - Cytochrome P450 monooxygenase system and acetylcholinesterase (AChE) activity were studied in the red swamp crayfish Procambarus clarkii sampled from the Ebro Delta before and after spraying of the area with fenitrothion. Analysis of hepatopancreas microsomes revealed an increase of 7-ethoxyresorufin O-deethylase (EROD) activity in organisms sampled after spraying. AChE activity was significantly inhibited in the same specimens, corroborating that these organisms were exposed to fenitrothion, and the usefulness of AChE as a marker of pesticide poisoning in P. clarkii. Crayfish from a reference site were analyzed and the results compared with those obtained in organisms from the Ebro Delta. The ability of P. clarkii to metabolize the organophosphorus pesticide fenitrothion was determined in vitro by using microsomal fractions isolated from hepatopancreas. The results pointed out the existence of an oxidative metabolism, which was inhibited by different P450 inhibitors (clotrimazole, alpha naphthoflavone and N-benzylimidazole) and not affected by methimazole. PMID- 9972476 TI - Cytochrome P450 and dependent activities in unexposed and PAH-exposed terrestrial annelids. AB - The cytochrome P450 system of the oligochaetes Eisenia f. fetida (tiger worm) and Enchytraeus crypticus (pot worm) was analysed using ethoxy-, pentoxy- and benzoxyresorufin as substrates for monooxygenase activity. Whole body microsomes of the earthworm E.f. fetida displayed PentROD activity in the range from 0.26 to 1.05 pmol mg protein-1 min-1 and BenzROD activity in the range from 0.14 to 0.30 pmol mg protein-1 min-1. Exposure of the animals for up to four weeks to 100 mg fluoranthene or benzo[a]pyrene kg-1 soil (dry weight) did not induce significant changes in the activity of these monooxygenases. In E. crypticus EROD activity was in the range from 2.10 to 6.18 pmol mg protein-1 min-1 and PentROD activity in the range from 1.75 to 4.78 pmol mg protein-1 min-1. Short-term exposure to BaP by feeding reduced the EROD activity significantly by 45%, but did not effect PentROD activity. After long-term (8 weeks) exposure to BaP in the agar-agar medium EROD activity was not changed but PentROD had decreased to zero. In both species cytochrome P420 and NADPH-cytochrome C reductase activity were present. In E.f. fetida microsomes are associated with the giant haemoglobin. Both can be separated by gel filtration on a Sepharose B2 column or by hydrophobic interaction chromatography after solubilisation with cholate. NADPH-cytochrome C reductase elutes together with haemoglobin. Cytochrome P420 is eluted with Emulgen 911 and can be further purified by ion exchange chromatography using HA Ultrogel. By SDS-PAGE of the purified microsomal proteins three protein bands are visualised in the range of cytochrome P450 displaying an apparent molecular mass of 54, 56 and 58 kDa. Only the 54-kDa protein interacts weakly with perch (Perca fluviatilis) CYP1A antibodies, while two proteins with an apparent molecular mass of 65 and 71 kDa give a strong antibody signal. PMID- 9972477 TI - A new cytochrome P450 (CYP30) family identified in the clam, Mercenaria mercenaria. AB - A full-length clone with sequence similarity to genes in the cytochrome P450 superfamily was isolated from a cDNA library prepared from female Mercenaria mercenaria gonadal tissue. This clone was isolated while screening an expression library with an antibody prepared against a peptide sequence within the ligand binding region of the murine Ah receptor. Comparison of the predicted amino acid sequence of this clone to those of other cytochrome P450 genes indicated that the closest overall sequence similarity (38%) was to proteins predicted from genes in the CYP3 family. Northern blots indicated the presence of a transcript of the appropriate size (3.0 kb) with homology to the clam cytochrome P450. In vitro translation of the cDNA clone produced a 50.7-kDa protein as determined by SDS polyacrylamide gel electrophoresis. The in vitro translated protein was not recognized on Western blots by two polyclonal antibodies specific for members of the CYP3 family. Since the degree of similarity to existing cytochrome P450 families was below the 40% level required for membership, and the expressed protein was not recognized by CYP3-specific antibodies, this clam cytochrome P450 cDNA has been placed in a new family, cytochrome P450 30 (CYP30). PMID- 9972478 TI - Immunochemical investigations of cytochrome P450 forms/epitopes (CYP1A, 2B, 2E, 3A and 4A) in digestive gland of Mytilus sp. AB - Western blot analysis of microsomes and partially purified cytochrome P450 (CYP) from digestive gland of Mytilus edulis was carried out using polyclonal antibodies to hepatic Perca fluviatilis CYP1A, Oncorhynchus mykiss CYP3A and rat CYP2B, CYP2E and CYP4A isoforms. Multiple CYP bands were detected in partially purified CYP compared to single bands for microsomes for anti-CYP1A, anti-CYP2B, anti-CYP2E and anti-CYP3A. In contrast, anti-CYP4A showed two distinct bands for both. The apparent molecular weights in kD (mean +/- range or S.D.; n = 2-4) for partially purified CYP were 42.5 +/- 0.5 and 48.1 +/- 0.3 (2 bands, anti-CYP1A); 67.4 +/- 0.7, 52.8 +/- 0.6, 44.5 +/- 2.5 (3 bands, anti-CYP3A); 52.8 +/- 0.7, 48.1 +/- 1.1 and 43.9 +/- 1.1 (3 bands, anti-CYP2B); 52.7 +/- 0.8 and 47.2 +/- 0.2 (2 bands, anti-CYP2E); 50.9 +/- 0.3 and 44.1 +/- 0.2 kD (2 bands, anti CYP4A). Digestive gland microsomes of Mytilus galloprovincialis from a polluted compared to a clean field site showed higher levels of bands recognised by anti CYP1A, anti-CYP2E and anti-CYP4A, but not anti-CYP2B and anti-CYP3A (P < 0.05), indicative of independent regulation of different CYP forms. Overall, the apparent molecular weight and field studies indicate at least five different digestive gland CYP forms. PMID- 9972479 TI - Spectral analysis and catalytic activities of the microsomal mixed-function oxidase system of the sea anemone (phylum: Cnidaria). AB - Cnidarians are primarily marine organisms with a wide and diverse habitat worldwide. Previous studies from our laboratory demonstrated the presence of proteins in the molecular mass range of 50-60 KDa that were recognized by several antibodies raised against fish cytochromes P450 of the CYP 1, 2, and 3 families in microsomes prepared from the columnar regions of 5 species of sea anemones (Heffernan et al. Mar Environ Res 1996;42:353-357). Pursuant to those studies we report herein results of spectral analyses, NAD(P)H-oxidoreductase and ethoxyresorufin O-dealkylase (EROD) of sea anemone microsomal fractions. The predominant feature in the difference spectrum of dithionite (DTN)-reduced, CO liganded anemone microsomes was a peak with lambda max of approximately 418 nm, which slowly increased for about 20 min and decreased after about 40 min. A relatively lower amplitude 450 nm peak was attained within 5 min of CO addition and was stable for up to 90 min. The 450 nm peak did not increase concomitant to the decrease in the 418 nm peak suggesting that the latter is not denatured P450. A significantly larger 450 nm peak was attained in CO-difference spectra when DTN was added prior to CO. NADPH-dependent cytochrome c (P450) reductase of the sea anemones was 1.8-3.9 nmol/min/mg protein, which is at the lower end of the range observed in invertebrates. NADH-cytochrome c reductase was 9-25 nmol/min/mg protein, while the NADH-ferricyanide (b5) reductase ranged from 73-232 nmol/min/mg protein. When microsomal EROD activity was measured under conditions in which the reaction was linear with respect to protein concentration, a decrease in fluorescence was typically observed for the initial 15 min of the time course and then increased linearly for up to 90 min; initial velocities were determined from the increasing linear region. NADPH was the preferred cofactor for EROD activity and the NAD(P)H-EROD activity was higher in Anthopleura elegantissima than Anthopleura xanthogrammica. The Bunodosoma cavernata NADPH EROD activity was barely noted at the detection limit of the assay and NADH-EROD activity was not detected. These results are consistent with a functional P450 dependent MFO system in cnidarians, with characteristics both similar to and unique from other marine invertebrates. PMID- 9972480 TI - The use of microsomal in vitro assay to study phase I biotransformation of chlorobornanes (Toxaphene) in marine mammals and birds. Possible consequences of biotransformation for bioaccumulation and genotoxicity. AB - The factors determining the bioaccumulation of lipophilic compounds in wildlife are often poorly understood, partly because it is difficult to do in vivo experiments with animals such as marine mammals and birds. To evaluate the role of phase I biotransformation in the bioaccumulation process of chlorobornanes (toxaphene), this was studied in in vitro assays with hepatic microsomes of animals that could be sampled shortly after death. The capacity of microsomes to metabolise a technical toxaphene mixture decreased in the order Phoca vitulina (harbour seal) >> Lagenorhynchus albirostris (whitebeaked dolphin) approximately equal to Diomedea immutabilis (Laysan albatross) > Physeter macrocephalus (sperm whale). Harbour seal microsomes metabolised the chlorobornane (CHB) congeners CHB 32 and CHB-62; whitebeaked dolphin and Laysan albatross microsomes only metabolised CHB-32. Metabolism of CHB-26 and CHB-50 was never observed. The negative chemical ionisation (NCI-) mass spectra of some of the hydroxylated metabolites were obtained. The number of peaks in the toxaphene residues of wildlife extracts decreased in the order of increasing in-vitro biotransformation capacity. Thus, the results of the in vitro assays and residue analysis were in accordance, although assays with microsomes of more individuals of the same species are required for a more general conclusion at the species level. Finally, the effect of in vitro biotransformation was evaluated in terms of the genotoxic potential using the Mutatox assay. Only technical toxaphene and CHB-32 were genotoxic in the direct assay, whereas the addition of rat S9 fraction or microsomes of harbour seal and albatross decreased the genotoxic response. Thus, organisms with a low ability to metabolise chlorobornanes, such as whales, may be most affected by the carcinogenic properties of toxaphene. A hypothetical reaction which fits the experimental results is discussed. Based on these results it is concluded that in vitro assays with microsomes of wildlife animals which died a natural cause can act as a valuable tool to assess the occurrence and effects of phase I metabolism. Some precautions are discussed, that should be taken to reduce the chance of false negative results. PMID- 9972481 TI - CYP1A-catalyzed uroporphyrinogen oxidation in hepatic microsomes from non mammalian vertebrates (chick and duck embryos, scup and alligator). AB - Uroporphyrin (URO) accumulation in the liver of animals treated with polyhalogenated aromatic hydrocarbons (PHAH) is associated with increased microsomal oxidation of uroporphyrinogen catalyzed by rodent CYP1A2 and by a similar form in chicken, CYP1A5. The planar biphenyl, 3,3',4,4' tetrachlorobiphenyl (TCB) stimulates uroporphyrinogen oxidation (UROX) in chick hepatic microsomes, but inhibits UROX activity in hepatic microsomes from mice and rats pre-induced by CYP1A2. Here we investigated whether TCB would stimulate or inhibit UROX in other non-mammalian species. UROX was stimulated 1.5-3-fold by TCB and 2-4-fold by 3,3',4,4',5,5'-hexachlorobiphenyl in hepatic microsomes from duck, alligator and scup treated with inducers of CYP1A. Hexachlorobenzene stimulated chick UROX, but was ineffective with microsomes from the other species. The stimulation of UROX by TCB was also observed in chick hepatocyte cultures. Pretreatment with up to 5 nM TCB induced CYP1A, but did not result in accumulation of URO. However, URO did accumulate if additional (post-induction) TCB was added along with 5-aminolevulinic acid. In this post-inductional TCB treatment, cycloheximide was included to prevent further induction of CYP1A. In duck hepatocytes, pretreatment with 25 nM TCB resulted in URO accumulation from 5 aminolevulinic acid. Post-induction TCB was not required and caused no further increase in URO accumulation. The differences in PHAH stimulation of UROX among the non-mammalian species have implications in the evolutionary changes in CYP1A, as well as the mechanism of development of PHAH-stimulated uroporphyria in different species. PMID- 9972482 TI - Screening for bacterial vaginosis. PMID- 9972483 TI - Images in Infectious Diseases in Obstetrics and Gynecology. Vaginal Lactobacillus phage plaques and electron micrograph. PMID- 9972485 TI - The ex vivo human placental transfer of the anti-HIV nucleoside inhibitor abacavir and the protease inhibitor amprenavir. AB - OBJECTIVE: The transfer of abacavir, a new nucleoside inhibitor, and amprenavir, a new protease inhibitor, used for the treatment of human immunodeficiency virus, has been studied in the ex vivo human placental model. METHODS: The ex vivo human placental model used C14 antipyrine to determine the transport fraction and clearance index of these compounds at both the peak and trough serum concentrations. The clearance index accumulation and tissue concentrations were determined for each drug by high pressure liquid chromatography. RESULTS: The clearance index of abacavir was 0.47 +/- 0.19 and 0.50 +/- 0.07 at peak and trough concentrations, respectively. The clearance index of amprenavir was 0.38 +/- 0.09 and 0.14 +/- 0.08 at peak and trough concentrations, respectively. There was no unusual accumulation of either drug in the media or tissue when the perfusion system was closed. CONCLUSION: Abacavir is the first nucleoside compound studied in the perfusion system with a high clearance index. The transfer of the protease inhibitor amprenavir had a clearance index 2.75 times greater than the clearance index of ritonavir at peak concentration determined in a previous study. At trough concentration the clearance index was much less than at the peak concentration. A similar result was found with ritonavir. PMID- 9972484 TI - Initial multicenter experience with double nucleoside therapy for human immunodeficiency virus infection during pregnancy. AB - OBJECTIVE: To study maternal and neonatal effects of combination nucleoside analog therapy administered to human immunodeficiency virus (HIV)-infected pregnant women for maternal indications. METHODS: A multicenter, prospective observational study was undertaken at six perinatal centers in the United States and Canada that supported regional referral programs for the treatment of HIV infected pregnant women. Demographic, laboratory, and pregnancy outcome data were collected for 39 women whose antiretroviral treatment regimens were expanded to include more than one nucleoside analog for maternal indications. The 40 newborns were monitored at pediatric referral centers through at least three months of age to ascertain their HIV infection status. RESULTS: For all 39 women, zidovudine (ZDV) therapy was instituted at 13.4 +/- 8.2 weeks, with a second agent (lamivudine [3TC] in 85% of cases) being added at a mean gestational age of 17.6 weeks. Duration of therapy with two agents was 20.6 +/- 10.4 weeks overall, with no women stopping medications because of side effects or toxicity. No significant changes in maternal laboratory values were seen, except for an increase in mean corpuscular volume, over the course of pregnancy. No clinically significant adverse neonatal outcomes were noted, with all but the three preterm newborns leaving hospital with their mothers. Neonatal anemia (hematocrit < 50%) was seen in 62% of newborns, with no children needing transfusion; mild elevations of liver function tests, primarily aspartate aminotransferase, were noted in 58% of newborns tested, though none were clinically jaundiced. Overall rate of neonatal HIV infection was 2.5% (95% confidence interval: 0.1-13.2%). CONCLUSION: Combination antiretroviral therapy during pregnancy with two nucleoside analogs was well-tolerated by mothers and newborns, with no significant short-term toxicities or side effects noted. Surveillance of exposed newborns' hematologic and liver function appears warranted. PMID- 9972486 TI - Assessment of office-based care of sexually transmitted diseases and vaginitis and antibiotic decision-making by obstetrician-gynecologists. AB - OBJECTIVE: Survey office-based obstetric-gynecologic practitioners regarding their knowledge of infectious disease care and antibiotic use. METHODS: A survey questionnaire of multiple-choice questions was mailed to Fellows of the American College of Obstetricians and Gynecologists about clinical entities for which recommendations have undergone recent changes or about which there was a lack of consensus in a prior similar survey (Gibbs RS, McGregor JA, Mead PB, et al.: Obstet Gynecol 83:631-636, 1994). RESULTS: Respondents indicated that oral metronidazole was their most frequent choice to treat bacterial vaginosis. Ampicillin (57%) was used more often than penicillin (39%) for intrapartum group B streptococcus prophylaxis. Azithromycin was preferred (61%) over erythromycin base (38%) for chlamydia treatment during pregnancy. There were several modes of practice that deviated from accepted care: 27% and 29% did not screen for chlamydia and gonorrhea, respectively, in pregnancy; 17% used cultures for Gardnerella vaginalis to diagnose bacterial vaginosis; 25% considered quinolones to be safe in pregnancy; 93% felt metronidazole should never be used in pregnancy; and the majority (66%) would send a patient treated successfully for pelvic cellulitis home with an oral antibiotic. CONCLUSION: Respondents' infectious disease knowledge and practices in obstetrics and gynecology is appropriate in treating sexually transmitted diseases, bacterial vaginosis, and group B streptococcus. Numerous deficiencies still exist in screening for sexually transmitted diseases in pregnancy and diagnosing bacterial vaginosis, as well as in the choice of antibiotics to use or avoid for certain infections. PMID- 9972487 TI - Frequency and yield of postoperative fever evaluation. AB - OBJECTIVE: In women undergoing major gynecologic surgery, we wish to determine the frequency and yield of blood culture, urine culture, and chest X-ray evaluation of postoperative fever. METHODS: A retrospective review of 537 consecutive patients undergoing major gynecologic surgery was performed. In patients who developed postoperative fever, it was determined whether blood culture, urine culture, and/or chest X-ray were performed, and, if so, the frequency of positive results was evaluated. RESULTS: Two hundred eleven patients (39%) developed postoperative fever. Blood cultures were obtained in 77 of 211 (37%) febrile patients, urine cultures in 106 of 211 (50%) febrile patients, and chest X-ray in 54 of 211 (26%) febrile patients. Zero of 77 blood cultures were positive, 11 of 106 (10%) urine cultures were positive, and 5 of 54 (9%) chest X rays were positive. Logistic regression revealed that late onset fever predicted for positive urine cultures and early onset fever and advanced age predicted for pneumonia. Eighty percent of patients with pneumonia were symptomatic. In 92% of patients with postoperative fever, no infections or pathologic process were diagnosed. CONCLUSION: Although postoperative fever is frequently evaluated by blood culture, urine culture, and chest X-ray, evaluation rarely yields positive results. PMID- 9972488 TI - The EAA International Quality Control Programme for Y-Chromosomal microdeletions. European Academy of Andrology. PMID- 9972489 TI - Classification of several types of maturational arrest of spermatogonia according to Sertoli cell morphology: an approach to aetiology. AB - Bilateral testicular biopsies and clinical histories from 34 adult men with maturational arrest of spermatogonia were examined. According to the morphology of Sertoli cell nuclei, five testicular types of spermatogonial maturational arrest were established. In type I lesion, Sertoli cells resembled the immature Sertoli cells of infant testes. These cells had a round, regularly outlined, dark nucleus with a small nucleolus. The seminiferous tubules showed no apparent lumen and a poorly developed lamina propria lacking in elastic fibres. This lesion was found in patients exhibiting a eunuchoid phenotype, with small tests and low serum levels of gonadotrophins and testosterone (hypogonadotrophic hypogonadism). Type II lesion showed morphologically normal, mature, adult Sertoli cells which had a pale, irregularly outlined nucleus, many often triangle-shaped, with a large, centrally located nucleolus. The seminiferous tubules were reduced in diameter and showed a few spermatocytes and spermatids. This lesion was found in patients with varicocoele, epididymitis, testicular trauma or idiopathic infertility. Serum FSH levels were normal or increased while LH and testosterone levels were normal. In type III lesion, Sertoli cells resembled the involuting Sertoli cells found in the testes of aging men, and displayed very infolded nuclei, with abundant dense chromatin patches and a large nucleolus. The seminiferous tubules showed a slightly dilated lumen and a normal tubular wall. The most relevant clinical findings in patients with this lesion were alcoholism, varicocoele, falciform cell anaemia, epididymitis and germ cell tumour. Serum follicle stimulating hormone (FSH) levels were normal or increased while luteinizing hormone (LH) and testosterone levels were normal. Type IV lesion Sertoli cells presented with a de-differentiated appearance. These cells had a small, round euchromatic nucleus with a small nucleolus and vacuolated cytoplasm. The seminiferous tubules were devoid of lumen or ectatic, and the tubular wall was thick and contained abundant elastic fibres. This lesion was characteristic of patients who underwent hormonal treatment because of prostatic carcinoma or sex change. Type V lesion showed abnormally differentiated, probably dysgenetic, Sertoli cells which had a round to ovoid regularly outlined nucleus, with small heterochromatin granules, and the number of these cells was increased. The seminiferous tubules had a central lumen, or were ectatic with vacuolated Sertoli cells, and the amount of elastic fibres was decreased. The most relevant clinical finding in patients with this lesion was orchidopexy. Serum FSH and LH levels were normal or slightly increased. These findings indicate that spermatogonial maturational arrest is associated with a characteristic Sertoli cell morphology that can be easily identified. This morphology may shed light on the aetiology of the disorder, and be useful for establishing the prognosis and bases for treatment in subfertile patients. PMID- 9972490 TI - Papanicolaou and Kruger assessment of sperm morphology: thresholds and agreement. AB - The current World Health Organization guidelines (1992) suggest that the presence of > or = 30% normal sperm forms (i.e. PAP criteria) is consistent with normal semen quality. Critical evaluation of sperm morphology (CE; Kruger classification) has shown an excellent correlation with human in vitro fertilization. Utilizing Kruger criteria, > 14% normal sperm forms has been proposed as indicative of normal semen quality. We have performed a retrospective analysis on 261 individuals to assess the agreement between PAP and Kruger criteria for normal sperm morphology (NSM). When the threshold for NSM by PAP was set at 30%, a significant agreement was found between the percentage normal forms of both criteria (Kappa coefficient = 0.37; p < 0.001). Sixty-seven (92%) of the 73 men found to have abnormal sperm morphology by PAP had abnormal semen by Kruger classification. When the threshold for NSM by PAP was established at 50%, the Kappa coefficient was 0.48 (p < 0.001). Sixty of the 72 samples (83%) classified as normal by PAP staining were normal by Kruger criteria. Interestingly, when NSM by PAP was between 30 and 50%, the specimen was just as likely to have normal or abnormal sperm morphology by Kruger (40 vs. 60%, respectively). These results strongly suggest that a high or low percentage of NSM by PAP is in agreement with the Kruger classification. The excellent agreement of Kruger and WHO criteria at the extremes (< 30% and > 50%) may obviate the need for Kruger assessment. However, when WHO morphology is between 30 and 50%, the addition of Kruger evaluation may provide meaningful information to help better diagnose a patient and plan his treatment. PMID- 9972491 TI - Lectin histochemistry of the human testis. AB - The oligosaccharide sequences of glycoconjugates and the nature of the saccharide linkage were investigated in normal human testes by means of lectin histochemistry studies, at light and electron microscopy levels. Reaction to WGA was intense in the seminiferous epithelium and interstitium. MAA showed light reactivity in all cell types of the human seminiferous epithelium, the lamina propria and Leydig cells. UEA-I lectin labelled the lamina propria intensely and the seminiferous epithelium and Leydig cells slightly. A slight reaction to AAA was found in the seminiferous epithelium and in Leydig cells. ConA was labelled in Sertoli cells, germ cells and Leydig cells. The reaction to GNA lectin was similar although less intense. PNA labelling was slight in Sertoli cells, spermatogonia, and Leydig cells, and more intense in spermatocytes, spermatids and peritubular cells. Reaction to DSA was intense in the seminiferous epithelium and Leydig cells. HPA labelled all cell types in the seminiferous epithelium and Leydig cells slightly, and labelled peritubular cells intensely. SBA lectin showed a strong reaction in spermatids and a slight reaction in the lamina propria. The reactions to SNA, LTA, and DBA were negative in all testicular cell types. After beta-elimination pre-treatment, MAA, UEA-I, AAA, PNA, DSA, HPA and SBA reactions were all negative. Endo F/PNGase digestion suppressed reactivity to ConA y GNA. Staining for WGA decreased with Endo F/PNGase digestion and also after beta-elimination. Desialization increased reactivity to PNA, SBA and HPA lectins. These results indicate that the terminal sequences of oligosaccharide side-chains in spermatocytes and, principally, in spermatids are: fucose, mannose, Neu5Ac2,3Gal1,3GalNAc, Gal1,3GalNAc, Gal1,4GlcNAc, Neu5AcGalNAc and GalNAc (in O-glycosylated proteins); mannose (in N-glycosylated proteins) and GlcNAc (in both protein types). A sialic acid residue is added to galactose and GalNAc residues. Present findings also indicate that Sertoli cell glycoproteins are similar to those of spermatids, and that the terminal sugar residues in Leydig cells are GlcNAc, fucose, mannose, Neu5Ac2,3Gal1,3GalNAc, Gal1,3GalNAc, and Gal1,4GlcNAc. The lectin pattern of the lamina propria suggests the presence of GlcNAc, galactose, fucose and GalNAc. PMID- 9972492 TI - Effects of ethanol ingestion on epididymal glycosidases and fertility in the rat. AB - Epididymal glycosidases play a role in sperm maturation by modifying sperm surface glycoproteins. To study the effects of ethanol on epididymal sperm maturation, ethanol (3 g/kg body weight as 25%, v/v) was administered to a group of rats by gastric-intubation twice daily for 30 days. In another group, rats were also treated with alcohol for 30 days but were then withdrawn from treatment for 30 days to assess the reversibility of ethanol-induced effects. Ethanol induced changes in epididymal tissue and sperm glycosidases, cauda epididymal sperm motility and the fertility of rats were assessed. Ethanol treatment caused a marked decrease in the specific activities of glycosidases in both tissues and spermatozoa from epididymal segments. Cauda epididymal sperm motility and the fertility of ethanol-treated rats were significantly impaired compared to control rats fed an isocaloric diet. These changes are likely to be the consequence of direct and indirect effects of ethanol mediated through subnormal testosterone and dihydrotestosterone. Most of these changes were found to be reversible. The present study suggests that impaired activity of sperm glycosidases may be one of the factors responsible for defective sperm motility and fertilizing potential in ethanol-treated rats. PMID- 9972493 TI - Higher thyroid hormone levels in neonatal life result in reduced testis volume in postpubertal bulls. AB - Thyroid hormones appear to determine adult testis size in rodents by regulating the period of Sertoli cell proliferation in the neonatal period. In the present study, the correlation between neonatal thyroid hormone levels (T3 and thyroxin, T4) and postpubertal testis size in Simental bulls was examined. T3 and T4 levels were measured in blood plasma from 35 calves immediately after their arrival at the AI centre at age 3-6 months. Testis size (height and width) was measured at 12 months of age in the same live animals. A significant negative correlation (r = -0.55; p < or = 0.001) was found between T4 and calculated testicular volume using either the Pearson correlation test or linear regression analysis, while the levels of T3 and testis volume showed a negative correlation, although this did not reach statistical significance (r = -0.20, p < or = 0.05). The results of this study suggest, therefore, that neonatal thyroid hormone levels might have the same effect on testicular size in cattle as they do in rodents. PMID- 9972494 TI - Effects of sauna on sperm movement characteristics of normal men measured by computer-assisted sperm analysis. AB - The effects of sauna exposure on sperm movement characteristics and other semen parameters were evaluated using computer-assisted sperm analysis (CASA). A significant (p < 0.01) decrease in average path velocity (VAP), curvilinear velocity (VCL) and amplitude of lateral head displacement (ALH) was found after exposure to sauna for 2 weeks. The altered parameters returned to their original values within 1 week after cessation of sauna exposure. Mean values for semen volume, sperm count, percentage motility, sperm morphology and sperm penetration assay (SPA) were not statistically different during and after sauna, when compared to the corresponding control values. The results suggest that increasing scrotal temperature by sauna causes a reversible decrease in sperm movement parameters. PMID- 9972495 TI - Tolerance to isosorbide dinitrate in isolated strips of rabbit corpus cavernosum. AB - The aim of this study was to investigate whether prolonged exposure to a high concentration of isosorbide dinitrate (ISDN) would result in tolerance being developed against its relaxant activity in strips of corpus cavernosum, pre contracted by phenylephrine. Under these conditions, relaxation induced by ISDN was found to be significantly reduced. Strips made tolerant to ISDN remained fully responsive to sodium nitroprusside and papaverine. Electrical field stimulation evoked relaxations which were persistent in the presence of tolerance inducing conditions. These results indicate that desensitization of guanylate cyclase activity is not likely to be the operating mechanism for nitrate tolerance. We suggest that tolerance may result from the impairment of biotransformation of ISDN in rabbit cavernosal smooth muscle. PMID- 9972496 TI - Immunohistochemical detection of testicular macrophages during the period of postnatal maturation in the mouse. AB - In the present study, the distribution of F4/80, a highly specific antigen of murine macrophages, was studied in the testes of maturing ICR mice to investigate postnatal development of testicular macrophages. The antigen was immunohistochemically identified at the light microscopic level on days 0, 7, 14, 21, 28 and 42 and at 8 weeks after birth. Only a few macrophages were present between developing seminiferous tubules on day 0, but by day 7, the cell density of macrophages in the interstitium was significantly increased. Although the cell processes of the macrophages were very short on days 0 and 7, it was found that their cell processes were extended on days 14 and 21. On day 28, it was observed that the cell density of macrophages increased further and their cell processes became longer, resulting in the formation of a network between adjacent macrophages. Thereafter, the interstitial spaces were found to be narrower due to the increasing diameter of developing seminiferous tubules, although similar physical contact between the testicular macrophages to that seen on day 28 was evident. Moreover, the cell density of macrophages at 8 weeks of age did not differ significantly compared with that on day 28. These results demonstrate that testicular macrophages develop rapidly for the first 4 weeks in the mouse testis. PMID- 9972497 TI - The spermatogenic cycle in the silver fox (Vulpes vulpes): frequency of the different stages prior to and during the breeding season. AB - In the silver fox the cycle of the seminiferous epithelium could be classified into eight characteristic stages defined on the basis of different, well-defined cell associations. The main criteria for the staging were the type of spermatogonia, the appearance of primary spermatocytes, the occurrence of meiotic figures and secondary spermatocytes and the shape and location of spermatids. In some cases more than one stage could be found within the same transverse tubular section. The average frequency of stages I to VIII was 25.2, 8.2, 9.0, 4.9, 16.2, 8.3, 10.7 and 17.5%, respectively. No significant difference was found between individuals sampled before and at the beginning and end of the breeding season. However, late in the season the migration of old spermatids and release of spermatozoa tended to be somewhat retarded, causing a slight increase in the duration and frequency of the last two stages of the cycle. PMID- 9972498 TI - Ketoprofen-poly(D,L-lactic-co-glycolic acid) microspheres: influence of manufacturing parameters and type of polymer on the release characteristics. AB - The effect of manufacturing parameters on the size and drug-loading of ketoprofen containing biodegradable and biocompatible poly(DL-lactic-co-glycolic acid) (PLGA) microspheres prepared by the solvent evaporation method was investigated. For both drug-free and drug-loaded microspheres, smaller microspheres with a narrower size distribution were obtained when the stirring rate or the volume of the organic phase was increased. Incorporation of ketoprofen was found to increase with increasing volume of the organic phase and decreasing pH of the aqueous phase, but was independent of the acidity and the inherent viscosity of the PLGA used. The biphasic release profile of ketoprofen from the microspheres was dependent on the type of PLGA as well as the size and drug-loading, two parameters governed by the manufacturing process. The first burst effect was found to increase with the drug content, reduction of size of the microspheres and increasing inherent viscosity of the matrix, whereas acidity of the PLGA had no effect on the release of this acidic drug. A vigorous first burst effect was associated with reduced sustained delivery of ketoprofen, the rate of the delayed release phase being dependent on the inherent viscosity of the matrix, the size, the payload and the pH during preparation of the microspheres. Thus, by selection of the manufacturing parameters and the type of PLGA, it is possible to design a controlled drug delivery system for the prolonged release of ketoprofen, improving therapy by possible reduction of time intervals between peroral administration and reduction of local gastrointestinal side effects. PMID- 9972499 TI - Effect of bead nutrient composition on regrowth of stored vitro-derived encapsulated microcuttings of different woody species. AB - Aseptic encapsulation in a sodium-alginate bead containing different nutritive solutions of microcuttings (uninodal explants excised from micropropagated shoots) of 10 different genotypes from four different woody species (Actinidia deliciosa, kiwifruit, cv Hayward and Tomuri; Malus spp,, apple, rootstock M. 26 and cv Starkspur Red and Wellspur; Olea europea, olive, cv Canino, Moraiolo, Ascolana tenera and Dolce Agogia; Rubus Idaeus, raspberry, Selection 1401) was investigated. The aim of the study was to evaluate the best nutritive formulation of the bead among seven different solutions, made of inorganic and organic compounds, growth regulators and sucrose, alone and combined, in order to maintain viability throughout 30 days of storage at 4 degrees C and subsequent regrowth ability of the encapsulated microcuttings on agarized medium, in view also of the possibility of inserting this storage phase in micropropagation cycles of these species. Olea plants gave interesting viability rates from 47.6 to 100% (according to cultivar and nutritive solution of the bead) immediately after storage, but the least satisfactory results in terms of regrowth, because of probable inadequacy of the culture medium. Actinidia, Malus and Rubus, instead, gave maximum rates in regrowth of 90.6% ('Hayward'), 83.3% ('M.26') and 83.4% ('Sel.1401'), respectively, and in sprouting of 62.5% ('Tomuri'), 75.0% ('M.26') and 77.2% ('Sel.1401'), respectively. Furthermore, encapsulated Rubus microcuttings proved usable also as synthetic seeds, with a maximum rooting (and conversion) rate of 60.7%. PMID- 9972500 TI - Preparation and characterization of ofloxacin microspheres for the eradication of bone associated bacterial biofilm. AB - Biodegradable polymers for localized delivery of antibiotics have emerged as an important approach to treating orthopaedic infections. In chronic forms of osteomyelitis which are thought to be associated with bacterial biofilm, localized delivery of a suitable antibiotic is desirable. This paper describes the formulation and in vitro evaluation of biodegradable ofloxacin microspheres for the eradication of bone associated bacterial biofilm infections. Ofloxacin microspheres were formulated using poly(glycolic acid-co-DL-lactic acid) (PGLA) by the emulsion solvent evaporation technique. The effects of process parameters such as phase volume, poly(vinyl alcohol) (PVA) concentration, and viscosity grade of the polymer during preparation on encapsulation efficiency (EEF) and in vitro release profiles were investigated. An increase in the phase volume or volume fraction from 21 to 35% at a constant internal phase volume resulted in an increase in EEF from 34 to 74%. Increasing PVA concentration from 0.25 to 2.5% w/v at a constant phase volume or volume fraction did not have an effect on the EEF. Ofloxacin release from the microsopheres was biphasic with an initial burst release followed by a slow release phase. An optimum slowing down of release was observed when the phase volume was 29%. Above and below this phase volume, release of ofloxacin was higher. The higher the viscosity grade of the polymer used for the preparation of microspheres, the higher the PVA concentration needed to prepare microspheres with slower release. The study indicates that various rates of ofloxacin release is possible by varying formulation conditions. This should provide a means for formulating sustained release microspheres of antibiotics for the treatment of biofilm infections associated with the bone. PMID- 9972501 TI - Effect of protective colloids on the induction of polymorphic changes in indomethacin agglomerates after solvent evaporation from o/w emulsions. AB - Indomethacin (IMC) agglomerates were prepared by the solvent evaporation process from o/w emulsions containing different protective colloids in the external aqueous solution. The types of protective colloids inducing the polymorphic transformation of IMC in the agglomerates without wall material were investigated. The composition and its polymorphs were evaluated from the X-ray diffraction patterns, IR spectra and DSC thermograms. The results indicate that when pectin, beta-cyclodextrin, sodium alginate or sodium dodecyl supphase acted as a protective colloid, the respective IMC agglomerates consisted only of the alpha form of IMC. When gelatin or hydroxypropyl methylcellulose was used as a protective colloid, the amorphous, alpha and gamma forms as well as methylene chloride solvates of IMC were found in the IMC agglomerates. There was only methylene chloride solvate of IMC with a small amount of amorphous form in the IMC agglomerates prepared from albumin as a protective colloid, while IMC agglomerates prepared from methylcellulose, polyvinyl alcohol or biosoluble polymer consisted of the mixture of amorphous and alpha forms, and methylene chloride solvate of IMC. When polyvinyl pyrrolidone was applied to act as a protective colloid, the mixture of methylene chloride solvate and gamma form of IMC with less quantity of amorphous form was found in its IMC agglomerates. This strongly suggests that the composition of IMC agglomerates prepared from the solvent evaporation process was significantly influenced by the type of protective colloids used. PMID- 9972502 TI - Particle size and loading efficiency of poly(D,L-lactic-co-glycolic acid) multiphase microspheres containing water soluble substances prepared by the hydrous and anhydrous solvent evaporation methods. AB - PLGA multiphase microspheres were prepared by the multiple emulsion solvent evaporation method using acetonitrile as the polymer solvent and mineral oil as the evaporation medium. The preparation process was further developed in the present study to reduce the particle size and to increase the loading capacity of brilliant blue, bovine serum albumin (BSA) and tumour necrosis factor-alpha (TNF alpha) which were used as water soluble model drug substances. Sorbitan sesqui oleate (SO-15EX), present at the 1% w/w level in the evaporation medium, prevented agglomeration of the microspheres containing a solid-in-oil (S/O) suspensions as the core phase. This S/O suspension core provided significantly higher loading efficiency of the proteins to the W/O emulsion core. The W/O emulsion system resulted in agglomeration of the protein-loaded microspheres and the loading efficiency decreased significantly. When brilliant blue was included as the model compound, the loading efficiencies were not influenced by the core type. Heavy mineral oil was employed to stabilize the dispersed unhardened microspheres rather than light mineral oil that was reported previously. This anhydrous emulsion system employing the S/O suspension core and containing a dispersion of TNF-alpha enabled the encapsulation of this protein without loss of activity. It was concluded that the anhydrous emulsion system is a suitable approach to prepare multiple microspheres as an alternative to the W/O emulsion system, especially when solvent sensitive proteins are incorporated into the microspheres. PMID- 9972503 TI - Stability determination of solid lipid nanoparticles (SLN) in aqueous dispersion after addition of electrolyte. AB - The contribution of mono-, di- and trivalent ions to the destabilization of solid lipid nanoparticle (SLN) dispersions was investigated, i.e. particle growth and subsequent formation of semi-solid gels. Sodium, calcium and aluminium chloride were added in varying concentrations to a Compritol formulation which had proved to be highly sensitive towards destabilizing effects. Dispersions containing up to 10(-3) M sodium chloride remained stable for 14 days. The same concentrations of calcium or aluminium induced slight and rapid particle growth, respectively. Generally, a pronounced destabilizing effect was observed with increasing electrolyte concentration and increasing valence. Higher concentrations of electrolyte (10(-2), 10(-1) M) induced gelation of the systems. The extent of solidification was highly dependent on the crystallinity of the lipid phase. The recrystalization indices of the gels were distinctly higher compared to the liquid systems. Additionally, unstable modifications, being present in liquid dispersions, were transformed into stable ones with increasing solidification. The mechanisms of the destabilizing effect of the electrolytes are reduced electrostatic repulsion and transformation of the lipid Compritol to the beta' modification promoting gel formation. PMID- 9972504 TI - Stability of chitosan and poly-L-lysine membranes coating DNA-alginate beads when exposed to hydrolytic enzymes. AB - Soluble chitosan and poly-L-lysine are readily hydrolysed using lysozyme or chitosanase for chitosan, and trypsin, chymotrypsin or proteinase K for poly-L lysine. For similar amounts of enzyme, chitosanase hydrolysed 57% of the chitosan, compared to 35% for lysozyme. In the case of poly-L-lysine, chymotrypsin and trypsin exhibited similar activities, hydrolysing approximately 41% of the polymer compared to proteinase K at only 16%. In contrast, chitosan and poly-L-lysine membranes, coating alginate beads, were almost totally inert to the respective hydrolytic enzymes. Less than 2% of the membrane weight was hydrolysed. It appears that either membrane material would be stable for in vivo application, and in particular in the protection of DNA during gastrointestinal transit. At chitosanase concentrations of 1.4 mg/ml and in the presence of sodium ions, 20% of the total double-stranded DNA was released from chitosan coated beads. An exchange of calcium for sodium within the bead liquefied the alginate core releasing DNA. The presence of calcium stabilized the alginate bead, retaining all the DNA. Highly pure DNA was recovered from beads through mechanical membrane disruption, core liquefaction in citrate and use of DNA spin columns to separate DNA/alginate mixtures in a citrate buffer. DNA recovery efficiencies as high as 94% were achieved when the initial alginate/DNA weight ratio was 1000. PMID- 9972505 TI - Comparative degradation study of biodegradable microspheres of poly(DL-lactide-co glycolide) with poly(ethyleneglycol) derivates. AB - The biodegradable polymers of poly(DL-lactide-co-glycolide) (PLGA) and poly(ethyleneglycol) (PEG) have come into use in the last few years for the control of the release of drugs. The incorporation of units of PEG produce an increased in vivo half life of the microparticles. The methoxylation of the PEG allows a control of the microparticles. The methoxylation of the PEG allows a control of the polymerization reaction by blocking one of the reactive terminals. An important aspect to be studied is the degradation of these polymers. The objective was centred on comparing the degradation that microspheres made of PLGA and PLGA-PEG (also with derivate methoxylated PEG). Degradation of the microspheres was studied at 37 degrees C and neutral pH. Samples were taken at different times to determine the size distributions, the mean diameter, the molecular weight and the structural composition of the polymer. The fastest decrease in Mw is observed in the case of PLGA microspheres. The PLGA-PEG microspheres show a significant size increase (from 24.6 to 90 microns) due to a swelling process. Any appreciable changes in Tg values were observed during the assay (30 days). PMID- 9972506 TI - Effect of drug properties on the release from CAP microspheres prepared by a solvent evaporation method. AB - Drugs with different water-solubility and molecular weights were microencapsulated in cellulose acetate phthalate, using an emulsion-solvent evaporation technique with a continuous oil-phase. The mean size of the particles was approximately 600 microns, and they were non-porous. The capacity of the microspheres to retain the drugs was evaluated by in vitro release studies in acidic medium. For low molecular weight compounds the release rates increased with solubility: for thiamin hydrochloride and phenacetin, a highly and a poorly soluble compound respectively, the percentages released at 60 min were 90 and 10%. Drugs with molecular weights above approximately 700 Da were retained in the microspheres. The above dependence on solubility was corroborated by release studies in ethanol, and by modelling the release of phenacetin in acidic media. Microspheres with a different polymer matrix, Eudragit RS PO, were also prepared by a similar technique, and these particles prolonged the release of thiamin for over 6 h, under simulated GI conditions. PMID- 9972507 TI - Biodegradable poly(DL-lactic-co-glycolic acid) microspheres containing tetracaine hydrochloride. In-vitro release profile. AB - Tetracaine does not result in effective treatment of intractable pain caused by trigeminal neuralgia because of its short duration of effect. In a sustained release system a controlled delivery of the drug at the site of administration, would avoid successive administrations. Tetracaine hydrochloride (HCl) has been encapsulated using a technique based on the evaporation of solvent from an O/O emulsion, using poly(DL-lactic-co-glycolic acid) (PLGA) 50:50. Microspheres were separated into three fractions: 106-212, 212-300 and 300-425 microns. The effects of two variables of the manufacturing method (volume of the inner phase of the emulsion and volume of surfactant added to the external phase) on the drug loading into microspheres, dissolution profiles and SEM characterization of the microspheres were evaluated. Microspheres containing tetracaine hydrochloride (up to 94% referred to the theoretical) released the drug, in-vitro, over 35 days. Tetracaine HCl was delivered according to zero order kinetics from day 5 until the end of the release assay. The rate of drug release depended mainly on the viscosity of the discontinuous phase and on the size of microparticles. Microsphere size resulted more homogeneous when using the highest volume of the surfactant, being almost 80% of microparticles within the range 212-300 microns. PMID- 9972508 TI - Mechanical strength of single microcapsules determined by a novel micromanipulation technique. AB - A micromanipulation technique has been developed to measure the bursting force of single dry microcapsules coated onto a surface, such as those normally used in carbonless copying paper. For measuring the bursting force of a given microcapsule, a single fine probe with a flat end about 10 microns in diameter was used to squeeze the microcapsule against a flat surface until it burst. The force being imposed on the microcapsule was measured by a transducer connected to the probe. The bursting force and diameter of single dry microcapsules in two samples, different in size and wall thickness, were measured by this technique. The bursting force of the microcapsules in one sample ranged from 50 to 220 microN and the diameter from 1.3 to 7.0 microns, whilst the bursting force in the other was from 20 to 175 microN and the diameter from 0.7 to 3.7 microns. This technique makes it possible to compare the mechanical strength of microcapsules made of different formulations, and to infer information about microcapsule mechanical properties. PMID- 9972509 TI - Recent developments in the management of retinoblastoma. AB - The management of retinoblastoma has gradually changed over the past few decades. There is a trend away from enucleation and external beam radiotherapy toward focal conservative treatments. This is primarily because of earlier detection of the disease and more focused treatment modalities. Enucleation is still employed for retinoblastoma that fills most of the eye, especially when there is a concern for tumor invasion into the optic nerve or choroid. After enucleation, an integrated orbital implant, provides improved motility and appearance of the prosthesis. External beam radiotherapy continues to be an important method of treating less advanced retinoblastoma, especially when there is diffuse vitreous or subretinal seeding. Plaque radiotherapy is useful for controlling small- to medium-sized retinoblastomas, even those with focal vitreous seeds. Tumors that recur after failure of other methods are often suitable for plaque treatment. When plaque radiotherapy is employed in a child receiving chemotherapy, eventual radiation retinopathy can occur. Cryotherapy and photocoagulation provide excellent control of selected small tumors. Advanced laser delivery systems, particularly those that have been adapted to the indirect ophthalmoscope, have facilitated the visualization for treatment of tumors. Thermotherapy is the newest focal method for retinoblastoma. When combined with chemotherapy, thermotherapy provides satisfactory tumor control, leaving the child with a reasonably small scar, thus preserving more vision. Chemoreduction, using intravenous or subconjunctival routes, is often employed to reduce initial tumor volume and thus allow for focal treatment to eradicate the residual smaller tumor. Many children with advanced retinoblastoma can be spared external beam radiotherapy and enucleation mostly as a result of chemoreduction and focal methods. Chemoreduction combined with cryotherapy, thermotherapy, and plaque radiotherapy plays an important role in the current management of many children with retinoblastoma. PMID- 9972510 TI - Outcome of occlusion treatment for amblyopia. AB - BACKGROUND: The purpose of this study was to determine the level of visual acuity following occlusion treatment for strabismic and anisometropic amblyopia and to analyze the factors that influence the outcome. METHODS: In this observational study, we examined the medical records of 246 patients discharged between April 1991 and March 1996, including those who failed to complete treatment. Two groups were identified: Group 1 esotropia (n = 151); and Group 2 anisometropic amblyopia with or without microtropia (n = 79). Factors influencing outcome of treatment were analyzed, success being defined as 6/12 or better in the amblyopic eye. RESULTS: In Group 1, 85% achieved 6/12 or better in the worst eye (linear acuity test), 15% achieved less than 6/12. (73% achieved 6/9 or better, 16% achieved 6/12 or 6/18, and 11% achieved less than 6/18). In group 2, 95% achieved 6/9 or better in the worst eye (linear acuity test); 5% achieved 6/12. CONCLUSION: Outcome was better than other full population studies to date. A good visual outcome was achieved in all cases of pure anisometropic amblyopia. Significant factors influencing outcome in the esotropic group were compliance, anisometropia, and visual acuity at start of treatment. An occlusion protocol is suggested aimed at further improving compliance and outcome. PMID- 9972511 TI - Refractive status in children after long-term follow up of cataract surgery with intraocular lens implantation. AB - PURPOSE: To evaluate the resultant refractive status in children 5 to 11 years after cataract surgery with a high power intraocular lens (IOL) implantation. METHODS: Charts of eight patients (10 eyes) who underwent cataract surgery with IOL implantation by the same technique were reviewed. Age at surgery was 2 months to 3 years. High-power IOL of 27.0 to 30.0 diopters (D) was implanted in seven eyes and lower IOL (between 19.0 D to 23.0 D) in three eyes. Follow-up period was between 5 and 11 years. RESULTS: In children who received a high-power IOL, the resultant refraction after 5 to 7 years was found to be between -5.50 and -12.00 D. In the group that had a lower power IOL implanted, the refraction was between 2.50 and +9.00 after 6 to 11 years. The results were plotted on a graph of refraction vs. IOL power and showed that the IOL power that may result in emmetropia in an older child is 23.2D. CONCLUSIONS: The implantation of a high power IOL (27 D to 30 D) in eight young children resulted in refractive status within 3 D of emmetropia during the first year or two of life and in high myopia at age 5 to 12 years. PMID- 9972512 TI - Strabismus: the first 3500 years. PMID- 9972513 TI - Ophthalmologic findings in the Dubowitz syndrome. PMID- 9972514 TI - Caffey-Silverman syndrome (infantile cortical hyperostosis) mimicking periorbital cellulitis. PMID- 9972515 TI - Absence of malignant hyperthermia in an infant with Wolf-Hirschhorn syndrome undergoing anesthesia for ophthalmic surgery. PMID- 9972516 TI - Penetrating orbitocranial knife injury. PMID- 9972517 TI - Familial congenital horizontal gaze palsy. PMID- 9972518 TI - The effects of nickel and cobalt ions on the spontaneous electrical activity, slow wave, in the circular muscle of the guinea-pig gastric antrum. AB - 1. Circular muscle strips of the guinea-pig gastric muscle produced spontaneous electrical activity in the form of slow waves. The slow wave amplitude, maximum rate of rise, duration, and frequency were 31 mV, 60 mV sec-1, 4.3 sec, and 4.3 min-1 on average, respectively. These parameters were not appreciably affected by 3 microM nifedipine or nicardipine, even following membrane depolarization with 60 mM K+. 2. Ni2+ (1-100 microM) increased slow wave amplitude and frequency, but reduced the rate of rise, accompanied by membrane depolarization. The rate of rise and depolarization slowly recovered to the control values in the continuous presence of Ni2+, but slow wave frequency remained high. The recovery after wash out was very poor particularly when a high concentration of Ni2+ was applied. 3. The effects of Co2+ were fundamentally the same as those of Ni2+. 4. Removal of external Ca2+ slowly reduced the rate of rise and amplitude of the slow waves in the absence and the presence of Ni2+ and Co2+, although the effects were reduced in the presence of these metal ions. 5. Concentrations of Ni2+ and Co2+ greater than 1 mM suppressed the slow waves. However, when the external Na+ was replaced with N-methyl-D-glucamine during the suppression, nearly normal electrical activity was resumed. 6. Since slow waves were not significantly affected by nifedipine (3 microM) and Ni2+ (100 microM), the inward currents generating slow waves do not seem to flow through L-type Ca2+ channels or typical T-type Ca2+ channels. Slow waves are probably potentiated by Ni2+ and Co2+ acting intracellularly. These ions at higher concentrations seem to inhibit the pacemaker activity more powerfully than they do the inward currents responsible for slow wave generation. PMID- 9972519 TI - Endothelium-independent relaxant effect of 5-hydroxytryptamine (5-HT) on the isolated rabbit facial vein. AB - The facial vein in several species has been shown to have unusual properties, including exhibition of spontaneous myogenic tone and relaxation to norepinephrine (NE). The present study was undertaken to characterize the relaxant effect of 5-hydroxytryptamine (5-HT) on the rabbit facial vein. An isolated ring preparation of the rabbit facial vein exhibited intrinsic tone when it was stretched and the spontaneous contraction continued for hours. 5-HT concentration-dependently relaxed facial veins exhibiting spontaneous contraction. The relaxation was not inhibited by rubbing the endothelium or by NG nitro-L-arginine (10(-4) M), a nitric oxide (NO) synthase inhibitor. The 5-HT induced relaxation was also unaffected by pretreatment with indomethacin (10(-5) M), a cyclooxygenase inhibitor, and propranolol (10(-6) M), a both beta adrenoceptor and 5-HT18-receptor antagonist. In contrast, 5-HT-induced relaxation of the facial vein was concentration-dependently antagonized by methysergide (10( 7) M and 10(-6) M), a non-selective 5-HT1- and 5-HT2-receptor antagonist, but not by NAN-190 (10(-6) M) and SDZ-205,557 (10(-6) M), antagonists for 5-HT1A- and 5 HT4-receptors, respectively. A higher (10(-6) M), but not lower (3 x 10(-7) M) concentration of ketanserin, a 5-HT2-receptor antagonist, slightly inhibited the 5-HT-induced relaxation. These results indicate that 5-HT-induced relaxation is not due to indirect mechanisms mediated by NE released from the sympathetic nerve terminals, or by endogenous prostanoid and endothelium-derived relaxing factor (EDRF = NO) released from the vascular tissues, but due to a direct effect on the 5-HT receptors located on vascular smooth muscle cells. However, the subtype of 5 HT receptor that produces relaxation of the rabbit facial vein remains to be clarified. PMID- 9972520 TI - Molecular cloning of m3 muscarinic acetylcholine receptor in rat iris. AB - Muscarinic receptor subtypes that involved in cholinergic responses in rat iris were identified by reverse transcription-polymerase chain reaction (RT-PCR) analysis. mRNAs encoding m2, m3, and m4 subtypes were abundantly expressed in iris, whereas m1 and m5 subtypes were not detected. Selective amplification of the coding regions of m2, m3, and m4 subtypes in iris was carried out using specific primers based on the sequence of each subtype previously cloned from rat brain and heart by RT-PCR. The amino acid sequence for iris m2 was different from published heart and genomic m2 by nine and one residue(s), respectively. It was also found that the sequence for m2 that in brain, heart, and several smooth muscles determined in the present study is completely identical to that in iris but not to that reported previously in heart. The sequence for iris m4 was completely identical to that for m4 in brain. The sequence identity between m3 subtype in iris and that in brain is 99.3%, with four amino acid substitutions at the sites of the position 165 and 184 in the edge of second intracellular loop and the sites of the position 337 and 406 in the central of i3 loop. It was found that iris m3 is slightly but substantially different in amino acid sequence from that in brain of the rat. PMID- 9972521 TI - Role of endothelium and adventitia on eugenol-induced relaxation of rabbit ear artery precontracted by histamine. AB - Eugenol (> or = 0.1 mM) inhibited the contractions induced by various stimulants, such as 90 mM extracellular K+ solution ([K+]0), histamine and noradrenaline in the rabbit ear artery. Inhibitory actions of eugenol occurred in a concentration dependent manner, however, eugenol more dominantly inhibited the histamine induced contraction than those induced by either 90 mM [K+]0 solution or noradrenaline. Removal of both endothelium and adventitia did not change the inhibitory actions of eugenol on the 90 mM [K+]0- and noradrenaline-induced contractions, however, attenuated those on the histamine-induced contraction. Chlorphenylamine abolished the histamine-induced contraction, but neither cimetidine, ranitidine nor thioperamide modified the eugenol actions on the contractions induced by histamine. Pretreatment with nitric oxide syntheses inhibitor NG-nitro-L-arginine (LNNA; 100 microM), but not soluble guanylate cyclase inhibitor methylene blue (MB; 10 microM), prevented endothelium/adventitia-dependent augmentation of the eugenol-induced relaxation on the histamine-induced contraction. When an intact tissue, but not an endothelium/adventitia-denuded tissue, was placed at the up-stream close to the other denuded preparation (test preparation), histamine-induced contraction observed in the test preparation tended to be augmented. Similarly, eugenol induced relaxation was also augmented by the same treatment. Eugenol (0.3 mM) inhibited the excitatory junction potentials (EJPs) without hyperpolarization of the membrane. However, a high concentration of eugenol (1 mM) slightly hyperpolarized the membrane (ca. 5 mV). No transient enhancement of amplitude of EJP was recorded. These results suggest that eugenol may inhibit the histamine induced muscle contraction directly, and the inhibition is augmented by the adventitia and endothelium partly by vasoactive substances, which were released from the adventitia/endothelium-derived substances in rabbit ear artery. PMID- 9972522 TI - Angiogenesis: possibilities for therapeutic interventions. AB - Vascular proliferation normally occurs only during embryonic development, the female reproductive cycle and wound healing. Various pathological conditions such as diabetic retinopathy are characterized by persistent, uncontrolled angiogenesis. At the other hand, impaired development of new blood vessels has been found to be related with myocardial infarction. A series of anti-angiogenic drugs are currently included in experimental cancer treatment, whereas the failure of ulcers to heal may be limited by increased angiogenesis upon administration of growth factors. In the present review control mechanisms of the vasculature are summarized and therapeutic approaches discussed. PMID- 9972523 TI - Informing women about drugs they take during pregnancy: promoting consumers' drug information as integral part of care. AB - Although it is recommended that drugs be avoided as much as possible during pregnancy, attitudes towards setting, time and method of the performed studies, and characteristics of the investigated population have been shown to vary. A collaborative and permanent network of different observational points is essential in monitoring and assessing the rational use of drugs, especially during pregnancy. In a context where knowledge is often scant and contradictory, the importance and the need for information on drug use during pregnancy remain unquestioned. If health (drug) information is the interface between those who produce and have knowledge and those who are beneficiaries of such knowledge, information for pregnant women (as well as for all lay people) is mandatory. Initiatives, people and instruments whose job it is to produce and diffuse informations have to be assessed and qualitatively harmonized to adequately answer to questions and needs. Women need information (concerning both pregnancy and drugs) on which to base choices on their own health care (and pregnancy). Clearly, this interaction depends on the kind of information and on the spirit with which it is provided. Thus it is essential that information (especially during pregnancy) be based on transparency and accountability, and it be directed by the principles of equity, effectiveness and affordability. PMID- 9972524 TI - Teaching and counselling behaviour: an applied study with community pharmacists. AB - Continuing education aims at improving practice. In this article, three main research questions are addressed: Which methodology is optimal to improve counselling behaviour? Are learning outcomes influenced by learning style? Does knowing imply doing? Four educational methods, transferring information on cough medicines, are assessed: a lecture, an interactive workshop, an audiocassette and a textbook. Attendants of the first three methods also received the textbook. Pharmacists completed a learning-style inventory in addition to a pretest. After the instruction phase, they were interviewed by telephone (post-test). We also evaluated the counseling behaviour by an 'incognito' visit to participants as well as to controls. Seventy-eight pharmacists participated. Their learning-style cannot be related to the results of pre- or posttest. Each educational method improved the level of knowledge significantly, but none of them proved to be better than the others. The pharmacists who in addition read the textbook, acquired more knowledge than those who did not. Self-study at home led to more fundamental rather than practical knowledge. Improving knowledge does not result in better counselling: 75% of the pharmacists asked only one question, especially concerning the type of cough. However 9 out of 10 mentioned how to use the drug. About half of the pharmacists told the patient about the action of the medicine. Other items were hardly ever mentioned. There was no difference in counselling behaviour between the intervention group and a group of pharmacists who did not attend the course. This investigation does not reveal any particular method of in service training as being more efficient. Active use of self-study materials helps to improve pharmacological knowledge. Implementing educational strategies to improve counselling behaviour remains a future aim. PMID- 9972525 TI - APOM-project: a survey of pharmacy organization and management. AB - In 1994, a Ph.D-study started regarding pharmacy, organization and management (APOM) in the Netherlands. The APOM-project deals with the structuring and steering of pharmacy organization. This article describes the summary of the empirical results of a survey in a relatively large sample (n = 169). Generalization to the population of pharmacies in the Netherlands was made. Thought results comprised a total number of seven clusters of priorities of pharmacy mixes. Most pharmacy managers were observed with product and customer activities in the first position; pharmaceutical and customer activities were perceived as the most important. Action results comprised a total number of five clusters of activities of pharmacy mixes. Most pharmacy managers were observed with product and process activities in the first position; pharmaceutical and process activities were performed most frequently. The results showed that the traditional conception of the work in the community pharmacy is still vividly present. PMID- 9972526 TI - Managing drug reactions to sulfonamides and other drugs in HIV infection: desensitization rather than rechallenge? AB - Drug reactions in patients with HIV infection, e.g. fever or rash, are a frequently occurring clinical problem. These side effects particularly are observed with sulfonamides; however, many other drugs have also shown to induce allergic reactions when given to patients with HIV infection. The production of hydroxylamines has been put forward as one of the explanations for these high incidence of reactions on drugs. Since sulfonamides are the first choice of therapy for the treatment and prophylaxis of Pneumocystis carinii pneumonia, several strategies have been developed to circumvent drug reactions. In general rechallenge or desensitization are recommended in literature. This article discusses the results and risks of rechallenge and desensitization with sulfonamides or other drugs, as mentioned in the literature. Furthermore preliminary results of rechallenge with a sulfonamide, which is not metabolized into hydroxylamines, are presented. From the data in the literature it is concluded that desensitization should be preferred to rechallenge. PMID- 9972527 TI - Can two-, four- or eight-hour urine collections after voluntary voiding be used instead of twenty-four-hour collections for the estimation of creatinine clearance in healthy subjects? AB - The accuracy of creatinine clearance estimations obtained from 4-hour (16:00 20:00, 20:00-24:00, 08:00-12:00, 12:00-16:00) and 8-hour (16:00-24:00, 24:00 08:00 and 08:00-16:00) urine collections and the Cockcroft Gault formula compared with the standard 24-hour collection, as well as the cyclical variation in creatinine excretion were studied in a group of 22 healthy subjects (Serum creatinine < 1.5 mg/dl, Blood Urea Nitrogen < 50 mg/dl) after voluntary voiding. The mean 4-hour and 8-hour creatinine clearances were not significantly different from the 24-hour values. Clearance values from 8-hour collections between 24:00 08:00 and 16:00-24:00 were found to be the most accurate and gave the best correlations. Furthermore only the mean absolute percentage deviations of the 8 hour from the 24-hour clearance values were significantly less than 20%. Significant cyclical variations in creatinine clearance over 24 hours were not observed. Time intervals between 23:00-07:00 and 07:00-09:00 were chosen for the comparisons between 8-hour, 2-hour, Cockcroft Gault creatinine clearance estimations and the 24-hour values in 21 healthy subjects. The mean 2-hour and 8 hour creatinine clearances were not significantly different from the 24-hour values. However, once again only the 8-hour clearance values differed by less than 20% from the 24-hour values and they were more accurate and better correlated than the 2-hour values. As expected, in both groups of subjects, the percentage of clearance values that deviated by more than 20% from the 24-hour values decreased as the length of the collection times increased. The Cockcroft Gault formula in both groups of volunteers gave less accurate clearance estimations, smaller correlation coefficients (not statistically significant in Group I subjects) and percentage deviations from the 24-hour values greater than 20%. Undetected early stage renal insufficiency in three volunteers and the use of actual instead of normalized Scr values may have been the cause of these poor clearance estimations. In healthy subjects (Scr < 1.5 mg/dl) 24-hour creatinine clearance may be estimated from an 8-hour urine collection with voluntary voiding if a 20% deviation from the 24-hour value is considered clinically acceptable. PMID- 9972528 TI - Risk for periodontal disease in a Swedish adult population. Cross-sectional and longitudinal studies over two decades. PMID- 9972529 TI - Immunephenotyping of T lymphocytes from patients after allogeneic bone marrow transplantation. AB - The relative distribution of T cell subsets as defined by MABs was analyzed in PBMCs from 56 patients with various hematologic diseases. The percentage of PBMCs expressing the CD5 antigen revealed normal values shortly after transplantation. In most patients lymphocytes expressing CD8 were found in high proportion and CD4 in a low percentage. This resulted in a low CD4/CD8 ratio compared with that of lymphocytes from normal controls. In the course of time, a trend toward normalization was observed for all parameters investigated, however the kinetics of the recovery showed a marked heterogeneity. Nevertheless, we found a statistical correlation between the CD4+ cell count and the PHA transformation response. This could however, not be shown in ConA and PWM stimulated proliferation. No other correlation was found between any lymphocyte phenotype, as defined by MABs, and proliferative responses in vitro. PMID- 9972530 TI - Studies on the migratory properties of epithelial cells of cholesteatoma: clinical investigation. AB - A total of 302 cholesteatoma cases were surgically treated with or without utilizing the cholesteatoma matrix to cover the defect of the eardrum. The recurrence rate, the number of days required for the skin to dry (epithelialization), findings of the external ear canal, the degree of postoperative crust formation (migration property), and the number of infections were compared between these two groups. Recurrence of cholesteatoma was seen in only one case, a case in which the cholesteatoma matrix was not used. The average number of days required for the skin to dry after surgery was 7.1 days in patients in whom the cholesteatoma epithelium was utilized, while it was 9.4 days in patients in whom cholesteatoma matrix was not utilized. The number of cases that had crust formation was significantly greater among patients in whom the cholesteatoma matrix was not utilized. From these results, we concluded that one stage tympanoplasty with mastoid obliteration using the cholesteatoma matrix is a rational surgical procedure. PMID- 9972531 TI - A clinical study of the nasal dilator Nozovent in Japanese subjects. AB - A nasal dilator (Nozovent) has been developed to fit in the nasal cavity and external nose of Caucasians, and beneficial effects have been confirmed. However, the ability of the device to dilate nasal valve areas of Orientals, whose external nose structure differs from that of Caucasians, has not been studied. We studied the effectiveness of the Nozovent device in preventing snoring and sleep apnea in Japanese subjects according to the methods described by Petruson. When the Nozovent device was worn by the eighteen subjects who experienced snoring, nine showed significant improvement, four showed good improvement, two fair improvement, and three discontinued the trial; the rate of improvement was 72.2%. The device was also seen to be effective for three patients with sleep apnea. The Nozovent device provides a unique method for non-surgical treatment of snoring, and the effectiveness is a result of dilatation of the nasal valve area. The principle is medically sound, and is equally applicable to nasal valves of both Caucasians and Japanese who have different external nose structures. PMID- 9972532 TI - Canal-down tympanoplasty; one-stage tympanoplasty with mastoid obliteration, for non-cholesteatomatous chronic otitis media associated with osteitis. AB - We operated on 54 ears using the canal-down procedure consisting of one-stage tympanoplasty with mastoid obliteration for non-cholesteatoma otitis media with lesions in the ossicular chain and compared the results with those of patients treated with the canal-up procedure. Complications, such as mastoid problems, which have been observed in surgery with the simple canal-down procedure, were not observed in operations combining mastoid obliteration. The success rate for our procedure as evaluated by postoperative hearing levels, according to the standards established by the Japan Society of Clinical Otology, Committee on Nomenclature 1987, was 77.4% with tympanoplasty (ceramic P type) with reconstruction of the ossicular chain; 70.6% with reconstructive surgery using T type ceramic; and 50.0% with reconstructive surgery using the patient's own bone. Overall, the success rate was 72.2%. Our procedure seems to be superior to the canal-up procedure with respect to improvement of hearing levels in the treatment of patients with chronic otitis media associated with lesions in the ossicular chain. PMID- 9972533 TI - Contribution of airway resistance to airway pressure during mechanical ventilation: an experimental study. AB - Although airway resistance (R) is an important parameter of the pulmonary condition, its determination during mechanical ventilation is not easy. Most physicians estimate R from peak airway pressure during mechanical ventilation. We assessed the relationship between R and peak airway pressure by a computer simulation. The time course of airway pressure (Ptr) during mechanical ventilation was calculated from the airway pressure at end-inspiration and respiratory flow, allowing for the buffering effect of the dead space. The parameters for computer simulation were obtained from 5 paralyzed and mechanically ventilated dogs. The predicted Ptr curve was a function of airway resistance. Since R was not directly determined by the animal experiments, we determined R by using the Ptr curve most closely approximating the original Ptr curve as the true R. The R-peak tracheal pressure relationship predicted by computer simulation showed that the peak airway pressure increased almost linearly with increases in R. However, in computer simulation, when R was increased 10-fold from the value at airway relaxation, the peak airway pressure increased only 6-fold from the corresponding value. We conclude that peak airway pressure is a relatively insensitive parameter for the estimation of airway constriction during mechanical ventilation. PMID- 9972534 TI - IgA nephropathy and pregnancy. AB - In the present study, we investigated the pregnancy course of 60 pregnant women with IgA nephropathy according to the grade of nephropathy. All the patients had undergone open renal biopsy at the Renal Metabolism Unit, Department of Internal Medicine, Tokai University Hospital, before pregnancy. The items analyzed were the serum biochemical data, the occurrence and severity of EPH-gestosis, the frequency of low birth weight infants, and the incidence of intrauterine growth retardation (IUGR). Analysis of the serum biochemical data revealed no statistically significant differences among the various grades. Investigating the occurrence and severity of EPH-gestosis revealed that the incidence was 0.0% in patients of grade I (n = 7), 56.1% for mild EPH-gestosis and 22.0% for severe EPH gestosis in those of grade II (n = 41), 45.5% for mild EPH-gestosis and 18.2% for severe EPH-gestosis in those of grade III (n = 11), and 0.0% in those of grade IV (n = 1). These results showed statistically significant differences in the incidence of EPH-gestosis according to the grade. Analyzing the frequency of low birth weight infants (less than 2,500 g at birth) showed rates of 28.6% for grade I, 17.1% for grade II, 36.4% for grade III, and 100.0% for grade IV. No statistically significant differences were observed. The incidence of IUGR was 0.0% for grade I, 9.8% for grade II, 18.2% for grade III, and 0.0% for grade IV, indicating no statistically significant differences. Therefore, we concluded that in pregnancy complicated with IgA nephropathy, if the renal function before pregnancy was satisfactory, an uneventful course of pregnancy could be expected by careful control of the patients, although the incidence of EPH-gestosis was high. PMID- 9972535 TI - Use of a glycoprotein gB promoter for expression of genes inserted into the human cytomegalovirus genome. AB - We attempted to utilize the human cytomegalovirus (HCMV) as an expression vector by replacing the dispensable genes of the viral genome with foreign genes. The selection of a promoter to be fused to the foreign gene is important to achieve a high expression rate in the recombinant virus. We selected the glycoprotein B (gB) promoter of HCMV as a target of analysis because gB is one of the most abundantly synthesized components in cell culture. The gB promoter, fused to the E. coli lacZ gene, was introduced into the HCMV HindIII-O fragment region by homologous recombination. It was confirmed that the gB promoter-lacZ construct was inserted in the targeted site of HCMV. The expression of the lacZ gene in the recombinant virus infection was initiated 24 h after infection and increased until 120 h post infection. The lacZ gene expression was inhibited by the presence of cytosine arabinoside. These observations indicate that the expression of the lacZ gene is under the control of the late promoter of gB. PMID- 9972536 TI - Anti-streptococcal activity of homologous polymorphonuclear neutrophils from patients with surgically treated oral infections. AB - The phagocytic bactericidal activity of homologous polymorphonuclear neutrophils (PMN), obtained from patients with severe, moderate and mild oral infections with Streptococci, was investigated. The drop in viable bacterial cell counts in PMNs from 3 patients with a severe infection, after 4 hours of incubation, was much greater than in PMNs from moderate or mild infections. We conclude that the phagocytic bactericidal activity of PMNs is stronger in patients suffering from severe oral infections with Streptococci. PMID- 9972537 TI - Experimental models and treatment trials for cerebral infarction. AB - Recent progress in both experimental and clinical studies of cerebral infarction is outlined, and research on delayed neuronal death and ischemic penumbra is described. Development of animal models to study clinical pathophysiology is reviewed, and our focal cerebral ischemia model which has been used for many years is introduced. With elucidation of the pathophysiology of cerebral ischemia, various pharmaceutical agents have appeared recently in the clinical setting and our experimental trials on the treatment of cerebral ischemia are also introduced. From the clinical aspect, practical methods of treatment including antiplatelet therapy are explained. Cerebrovascular dementia and its prevention are also described. PMID- 9972538 TI - Three cases of primary lung cancer undetected by an annual checkup. AB - An annual check by chest roentgenogram is very important for the early detection of lung cancer. We present three cases of primary lung cancer which were not detected by the double check system or previous examination. The three patients visited our hospital for evaluation of an ill-defined opacity in the upper lobe of the lung. In the three cases, no abnormality had been reported in the previous year's annual chest X-ray, and we concurred in the decisions. The correct diagnoses of the three cases were well or poorly differentiated adenocarcinoma, and were still amenable for surgical therapy. A poorly defined tumor in this region is very difficult to detect because of superimposed opacities of other anatomical structures. When a questionable shadow in this region is found but without the typical radiological features of lung cancer, it is important to search for indirect indications of adenocarcinoma. These may include fibrotic changes and absence of inflammation. In our cases, the increased number of normal size bronchi penetrating the ill-defined tumor, seem to have diagnostic significance. PMID- 9972539 TI - Can postoperative abdominal wound dehiscence be predicted? AB - The purpose of this study was to identify risk factors in wound dehiscence and to determine which factors might be predictable. Forty patients with abdominal wound dehiscence were compared with 40 control patients standardized by sex and age. Hypoproteinemia, nausea/vomiting, fever, wound infection, abdominal distension, type of suture material, 2 or more abdominal drains, and the surgeon's experience were factors significantly associated with wound dehiscence. Emergency surgery, jaundice, ostomy, total parenteral nutrition, ascites, pulmonary morbidity, co existence of disease, anemia, leucocytosis, and type of incision were nonsignificant variables. The number of patients with wound dehiscence increased with an increase in the number of risk factors, reaching 100% for patients with 8 risk factors. The risk factors of wound dehiscence can be predicted early and their number can be decreased before and after surgery by an experienced surgeon, leading to a lowered incidence of wound failure. PMID- 9972540 TI - Mechanisms of excitatory synaptic transmission in the enteric nervous system. AB - The enteric nervous system can control gastrointestinal function independent of direct connections with the central nervous system. Enteric nerves can perform this task as there are multiple mechanisms of excitatory neurotransmission in enteric ganglia. There are two broad types of excitatory synaptic transmission, fast and slow excitatory synaptic responses. Fast excitatory postsynaptic potentials (fEPSPs) are recorded from "S" type neurons and some AH type neurons. S neurons are interneurons and motorneurons while AH neurons are intrinsic sensory neurons. Slow excitatory postsynaptic potentials (sEPSPs) can be recorded from some S neurons and also from AH type neurons. The fEPSPs recorded from S neurons and mediated largely by acetylcholine acting at nicotinic cholinergic receptors (nAChRs). However, ATP acting at P2X purine receptors contributes to the fEPSP in many S neurons. The fEPSPs recorded from AH neurons are also mediated largely by nAChRs but glutamate acting at AMPA receptors contributes to fEPSPs in some AH neurons. The sEPSPs in AH neurons are mediated by one or more neuropeptides and 5-hydroxytryptamine. The sEPSPs in AH neurons are due to inhibition of two types of resting potassium channels and activation of a chloride channel or a nonspecific cation channel. The multiple mechanisms of excitatory synaptic transmission in the enteric nervous system contribute to its capacity to regulate complex gastrointestinal functions. PMID- 9972541 TI - Social support as a function of school counseling. AB - The objective of this study was to investigate the value of school counseling, particularly in terms of social support. To prepare this report, I conducted a follow-up study on graduates of T high school, on school counseling, based on 185 individuals. I compared the students who received counseling when they were in school (visitants) with students who did not (non-visitants), and examined the correlation between them. As a result, significant statistical differences were detected as follows: 1. The visitants had different concerns from the non visitants. 2. The visitants had a variety of individual concerns. 3. The visitants differed in the manner of obtaining social support. 4. Both groups had their own characteristic categories of social support. Consequently, two conclusions have been drawn: 1. Extensive informal relationship with friends exists among high school students. In particular, club and extracurricular activities are of major importance. 2. When informal support is not available, help may be sought from formal relationships (counselor, teachers of handicapped students, or classroom teachers). In other words, school counseling can function as a complementary and effective social support for high school students. PMID- 9972542 TI - Collagen production by cultured human retinal pigment epithelial cells. AB - We investigated extracellular matrix produced by human retinal pigment epithelial cells (RPE) in vitro using electron microscopy and enzyme linked immunosorbent assay (ELISA). The thickness of the matrix under the cell layer was about 30 microns after 360 days of culture. It consisted mainly of fibrous and granular components. Type IV and V collagen were detected but type I and III were not detected by ELISA. It appeared that RPE can secrete type IV and V collagen and form a thick membrane which may cause proliferative vitreoretinopathy (PVR) by contraction. Control of RPE proliferation and secretion of extracellular matrix is indispensable for prevention of PVR. PMID- 9972543 TI - Colonic adenoma detected by positron emission tomography (PET): a case report. AB - A 61-year-old asymptomatic woman underwent whole-body positron emission tomography (PET) with 18F-fluorodeoxyglucose and was found to have a lesion in the ascending colon. Further colonic examination was not performed due to her medical condition. One year later, the lesion was demonstrated again by PET. After the second PET study, she underwent colonoscopy, which revealed a pedunculated polyp in the ascending colon. A polypectomy was performed. Histopathological study showed a 1.8-cm adenoma with mild to moderate atypia. The findings in our case suggest that increased glucose metabolism can be depicted by PET in colonic adenoma as well as in primary colonic carcinoma. Although the differentiation between colonic adenoma and carcinoma can not be determined by PET, adenomas are considered to have potential for malignant transformation and thus need to be resected. Therefore, it is noteworthy that PET can be used in the detection of adenomas. PMID- 9972544 TI - Characterization of the damage to membranes caused by bacterial cytolysins. AB - The damage to cell membranes caused by bacterial cytolysins has been studied for many years. In this review, we attempt to summarize the historical contribution of electron microscopy to our understanding of the modes of action of pore forming and channel-forming toxins. We describe the ways in which these toxins form holes in membranes by binding to and forming oligomers on biological membranes. We also introduce the new technique of electron spectroscopic imaging (ESI) with an imaging plate (IP), which has been used to analyse the mechanisms of membrane damage by cytolysins. PMID- 9972545 TI - Ultrastructural variations of rat myocardium due to Walterinnesia aegytia snake envenomation. AB - This study was undertaken to investigate the toxic effect of Walterinnesia aegyptia venom on the ultrastructure of rat myocardium. Male albino rats were prepared for intraperitoneal injection of saline (control group) and saline solution of W.aegyptia venom (study group) at a dose of 0.04 mg animal-1. Biopsies from the left ventricle were prepared for electron microscopy after 1 h (D1 group), 2 h (D2 group), 18 h (D3 group) and 24 h (D4 group). Myocardial cells were in a state of partial to complete contraction. The D1 group showed some mitochondrial vacuoles; D2 group demonstrated more vacuolation and alterations in the form of disorganized cristae. Similar findings were depicted in D3 group. The D4 group demonstrated, in addition, dissolution of mitochondrial cristae. Myofilaments in D3 group experienced coalescence into ill-defined amorphous masses (foci of myolysis). These masses were characterized by the presence of multiple, parallel, Z-like dark bands with disorganization of the filamentous arrangement. In the D4 group, more myolytic foci were observed. This reaction was not limited to one myocyte but extended to the neighbouring ones. Mitochondrial vacuoles were mostly associated with electron dense deposits. Glycogen particles tended to decrease as the experiment proceeded from D1 to D4. These ultrastructural changes were time dependent. They would suggest a cardiotoxic action of W.aegyptia snake venom. PMID- 9972546 TI - Ultrastructural localization of tartrate-resistant acid phosphatase activity in rat osteoblasts. AB - Ultrastructural localization of tartrate-resistant acid phosphatase (TRAP) activity in metaphyseal osteoblasts of young rats was detected and compared with the localization of tartrate-sensitive acid phosphatase (TSAP). TRAP activity was detected in lysosomes and Golgi complex, such as Golgi lamellae, vacuoles and vesicles. TSAP, detected as beta-glycerophosphatase, was also located in Golgi lamellae, vacuoles and vesicles, and in lysosomes. Based on the ultrastructural features of TRAP-positive structures and the similarity of the distribution patterns of TRAP and TSAP, it is suggested that TRAP co-exists with TSAP, and is located in lysosomes and secretory granules in osteoblasts. PMID- 9972547 TI - Two statoacoustic ganglion (SAG) cells holding a common perikaryal myelin sheath in between in the chick. AB - Ganglion cells of the eighth cranial nerve in vertebrates have perikaryal myelin sheaths. The present electron microscopic study showed a case of two statoacoustic ganglion (SAG) cells holding a common perikaryal myelin sheath in between in the chick. Observations of numbers and terminals of myelin lamellae suggested that the sheath would be composed of an abortive lamella sandwiched between respective perikaryal myelin sheaths of the two SAG cells. The outer surface of the two perikaryal sheaths was covered by a continuous basal lamina. The process of common myelin sheath formation is discussed. PMID- 9972548 TI - Molecular structure of human topoisomerase II alpha revealed by atomic force microscopy. AB - The entire human topoisomerase II alpha (hTopoII alpha) dimer was expressed in the yeast Saccaromyces cerevisiae, purified to homogeneity, and subjected to atomic force microscopy (AFM) under a tapping mode. Molecular images obtained exhibited a 'heart or donut-like' structure with a large axial hole. The main benefit of the application of AFM to study the hTopoII alpha is that clear images of the internal 'pore' have been achieved without crystallization, staining, or fixation of the sample. These images are consistent with the model in which topoisomerase II has a large internal gate for DNA strand passage. PMID- 9972549 TI - In search of self-definition: motivational primacy of the individual self, motivational primacy of the collective self, or contextual primacy? AB - Four investigations examined the dynamics between the individual self (self representation independent of group membership) and the collective self (self representation derived from group membership). Relative to participants whose collective self was threatened, participants whose individual self was threatened (a) considered the threat more severe, (b) experienced a more negative mood, (c) reported more anger, and (d) derogated to a greater extent the source of threat. In addition, a self-description task indicated that participants generate more aspects of their individual than collective self. These effects occurred even when confounding variables (i.e., accessibility of the selves, group identification, individualism and collectivism, importance of threat domain) were controlled. The individual self is motivationally primary. PMID- 9972550 TI - Stigmatized sources and persuasion: prejudice as a determinant of argument scrutiny. AB - Two experiments examined the viability of several explanations for why majority group individuals process persuasive messages from stigmatized sources more than those from nonstigmatized sources. In each study, majority group participants who either were high or low in prejudice or were high or low in ambivalence toward a stigmatized source's group were exposed to a persuasive communication attributed to a stigmatized (Black, Experiment 1; homosexual, Experiment 2) or nonstigmatized (White, Experiment 1; heterosexual, Experiment 2) source. In both studies, source stigmatization increased message scrutiny only among those who were low in prejudice toward the stigmatized group. This finding is most consistent with the view that people scrutinize messages from stigmatized sources in order to guard against possibly unfair reactions by themselves or others. PMID- 9972551 TI - The impact of mortality salience on reckless driving: a test of terror management mechanisms. AB - A series of 4 studies, based on terror management theory (TMT), examined the effects of mortality salience on risk taking while driving. In all the studies, participants (N = 603) reported on the relevance of driving to their self-esteem. Then half of them were exposed to various mortality salience inductions, and the remaining to a control condition. The dependent measures were either self reported behavioral intentions of risky driving or driving speed in a car simulator. In Study 4, half of the participants in each condition received positive feedback about their quality of driving. Findings showed that mortality salience inductions led to more risky driving than the control condition only among individuals who perceived driving as relevant to their self-esteem. The introduction of positive feedback about driving eliminated this effect. The results were discussed in light of the self-enhancing mechanisms proposed by TMT. PMID- 9972552 TI - "I love you more today than yesterday": romantic partners' perceptions of changes in love and related affect over time. AB - Partners in romantic relationships provided reports on perceived changes in their love, commitment, and satisfaction and completed contemporaneous scales on the same relationship phenomena multiple times over several years. At each wave of the longitudinal study, participants whose relationships had remained intact perceived that their love and related phenomena had increased since they had last participated in the study. However, their scores on contemporaneous scales did not generally increase over time. Analyses indicated that participants' reports of change were related to actual change in love, commitment, and satisfaction scores and with future relationship stability. Furthermore, participants who experienced a breakup during the longitudinal study reported an overall decrease in their positive affect in the months prior to the breakup. PMID- 9972553 TI - Couple resilience to economic pressure. AB - Over 400 married couples participated in a 3-year prospective study of economic pressure and marital relations. The research (a) empirically evaluated the family stress model of economic stress influences on marital distress and (b) extended the model to include specific interactional characteristics of spouses hypothesized to protect against economic pressure. Findings provided support for the basic mediational model, which proposes that economic pressure increases risk for emotional distress, which, in turn, increases risk for marital conflict and subsequent marital distress. Regarding resilience to economic stress, high marital support reduced the association between economic pressure and emotional distress. In addition, effective couple problem solving reduced the adverse influence of marital conflict on marital distress. Overall, the findings provided substantial support for the extended family stress model. PMID- 9972554 TI - Ideals in intimate relationships. AB - This research examined lay relationship and partner ideals in romantic relationships from both a social-cognitive and an evolutionary perspective. Studies 1 and 2 revealed that the qualities of an ideal partner were represented by 3 factors (partner warmth-trustworthiness, vitality-attractiveness, and status resources), whereas the qualities of an ideal relationship were represented by 2 factors (relationship intimacy-loyalty and passion). A confirmatory factor analysis in Study 3 replicated these factor structures but found considerable overlap across the partner and relationship dimensions. Studies 4 and 5 produced convergent and discriminant validity evidence for all 5 factors. Study 6 indicated that the higher the consistency between the ideals and related assessments of the current partner and relationship, the more positively the current relationship was evaluated. PMID- 9972555 TI - Laypeople's conceptions of commitment. AB - The author conducted 8 studies to elucidate the content and structure of lay conceptions of commitment. Studies 1 to 5 revealed that laypeople regard commitment to close relationships (e.g., friends, family, spouse) as central to the concept, whereas they consider nonclose (e.g., commitment to a neighbor) and noninterpersonal varieties (e.g., one's occupation) peripheral. This prototype structure influenced information processing in predictable ways. Studies 6 to 8 focused on the vertical structure of commitment categories. Results suggest that types of commitment are organized as fuzzy rather than true class-inclusion hierarchies. Study 8 also examined relationship implications of conceptions of commitment. People who held a relational conception of commitment had more positive perceptions, thoughts, and feelings about their dating relationship than did those who held a nonrelational conception. PMID- 9972556 TI - Effects of optimism, pessimism, and trait anxiety on ambulatory blood pressure and mood during everyday life. AB - This study tested whether dispositional measures of optimism, pessimism, and anxiety affected ambulatory blood pressure (BP) and mood and whether any cardiovascular effects of dispositions were moderated by mood. Pessimistic and anxious adults had higher BP levels and felt more negative and less positive than did optimists or low anxious adults throughout the monitoring. The few times that optimists did feel negative were associated with levels of BP as high as those observed among pessimists or anxious individuals, regardless of their mood. To the extent that trait anxiety measures neuroticism, these findings suggest that neuroticism is directly related to health indicators rather than simply to illness behavior. Furthermore, the results suggest that pessimism has broad physiological and psychological consequences. PMID- 9972557 TI - Stigma consciousness: the psychological legacy of social stereotypes. AB - Whereas past researchers have treated targets of stereotypes as though they have uniform reactions to their stereotyped status (e.g., J. Crocker & B. Major, 1989; C. M. Steele & J. Aronson, 1995), it is proposed here that targets differ in the extent to which they expect to be stereotyped by others (i.e., stigma consciousness). Six studies, 5 of which validate the stigma-consciousness questionnaire (SCQ), are presented. The results suggest that the SCQ is a reliable and valid instrument for detecting differences in stigma consciousness. In addition, scores on the SCQ predict perceptions of discrimination and the ability to generate convincing examples of such discrimination. The final study highlights a behavioral consequence of stigma consciousness: the tendency for people high in stigma consciousness to forgo opportunities to invalidate stereotypes about their group. The relation of stigma consciousness to past research on targets of stereotypes is considered as is the issue of how stigma consciousness may encourage continued stereotyping. PMID- 9972558 TI - Individual differences in social comparison: development of a scale of social comparison orientation. AB - Development and validation of a measure of individual differences in social comparison orientation (the Iowa-Netherlands Comparison Orientation Measure [INCOM]) are described. Assuming that the tendency toward social comparison is universal, the scale was constructed so as to be appropriate to and comparable in 2 cultures: American and Dutch. It was then administered to several thousand people in each country. Analyses of these data are presented indicating that the scale has good psychometric properties. In addition, a laboratory study and several field studies are described that demonstrated the INCOM's ability to predict comparison behavior effectively. Possible uses of the scale in basic and applied settings are discussed. PMID- 9972559 TI - The interaction model of anxiety and the threat of Quebec's separation from Canada. AB - The interaction model of anxiety was investigated by assessing trait and state anxiety in students at a Canadian university during the Quebec referendum. The results of Study 1 confirmed that the threat of separation by Quebec from Canada was perceived as an ambiguous, uncertain situation. In Study 2, reactions to this situation were assessed by having participants complete measures of anxiety and situation perception at Time 1 (i.e., 3 hr before the event) and Time 2 (i.e., 1 week after the vote). The results provide support for the interaction model; individuals who were high in trait anxiety in ambiguous situations and appraised the referendum situation as threatening were characterized by elevated state anxiety before the uncertain outcome of the vote. The results illustrate the need to examine trait anxiety and specific appraisals of situational threat in uncertain life situations. PMID- 9972560 TI - Symmetry and perceived facial attractiveness: a monozygotic co-twin comparison. AB - Symmetry is a major correlate of physical attractiveness across species, including humans. Investigating the nature of this relationship has been difficult, however, for several reasons, including the facts that variance in symmetry is attributable to more than one source and is often correlated with other variables related to attractiveness. This study assessed the role of facial symmetry in relation to perceptions of facial attractiveness. Some of the natural covariates of symmetry were controlled for by comparing the symmetry and attractiveness differentials between monozygotic co-twins, who are genetically, but not developmentally, identical. The more symmetric twin of a pair was consistently rated as more attractive, and the magnitude of the difference between twins in perceived attractiveness was directly related to the magnitude of the difference in symmetry. PMID- 9972561 TI - Fluctuating asymmetry, sociosexuality, and intrasexual competitive tactics. AB - Heterosexual men and women were told they were competing with another same-sex individual for a date with an attractive opposite-sex interviewer. After answering 6 questions, participants were asked to tell the competitor why the interviewer should choose them over the competitor. Participants' videotaped behavior was coded for different behavioral tactics. Men who were more symmetrical and who had a more unrestricted sociosexual orientation were more likely to use direct competition tactics than were less symmetrical and restricted men. Restricted men accentuated their positive personal qualities, presenting themselves as "nice guys." Structural equation modeling revealed that fluctuating asymmetry (FA) was directly associated with the use of direct competition tactics. However, the link between FA and presenting oneself as a nice guy was mediated through sociosexuality. No effects were found for women. PMID- 9972562 TI - Aeroelastic structural acoustic control. AB - Static, constant-gain, output-feedback control compensators were designed to increase the transmission loss across a panel subjected to mean flow on one surface and a stationary, acoustic half-space on the opposite surface. The multi input, multi-output control system was based upon the use of an array of colocated transducer pairs. The performance of the static-gain, output-feedback controller was compared to that of the full state-feedback controller using the same control actuator arrays, and was found to yield comparable levels of performance for practical limitations on control effort. Additionally, the resulting static compensators proved to be dissipative in nature, and thus the design varied little as a function of the aeroelastic coupling induced by the fluid-structure interaction under subsonic flow conditions. Several parametric studies were performed, comparing the effects of control-effort penalty as well as the number of transducer pairs used in the control system. PMID- 9972563 TI - Insights into linear and nonlinear cochlear transduction: application of a new system-identification procedure on transient-evoked otoacoustic emissions data. AB - Transient-evoked otoacoustic emissions (TEOAE) were used to characterize linear and nonlinear cochlear transduction using a new system-identification procedure. In this technique, a computational model of the system is first developed. From the measured stimulus and response records, spectral-density functions and multiple coherence functions are calculated. The coherence functions allow the characterization of linear/nonlinear processes as a function of frequency. Summations of linear and nonlinear coherences provide a goodness-of-fit of the chosen model. Finite impulse response pulses with a bandwidth of 1-8 kHz were used to evoke otoacoustic emissions. Eleven adults with normal hearing served as subjects. Third- and fifth-order polynomial models were used to model the data, and the results indicate that the fifth-order model is a better fit to the TEOAE data. The results of this study suggest that this system-identification procedure can be successfully applied to model cochlear transduction using a broadband stimulus. Most importantly, coherence functions provide useful insights into linear and nonlinear cochlear processes and have the potential to be developed as a clinical measure for monitoring changes in cochlear status. PMID- 9972564 TI - Evoked otoacoustic emissions arise by two fundamentally different mechanisms: a taxonomy for mammalian OAEs. AB - Otoacoustic emissions (OAEs) of all types are widely assumed to arise by a common mechanism: nonlinear electromechanical distortion within the cochlea. In this view, both stimulus-frequency (SFOAEs) and distortion-product emissions (DPOAEs) arise because nonlinearities in the mechanics act as "sources" of backward traveling waves. This unified picture is tested by analyzing measurements of emission phase using a simple phenomenological description of the nonlinear re emission process. The analysis framework is independent of the detailed form of the emission sources and the nonlinearities that produce them. The analysis demonstrates that the common assumption that SFOAEs originate by nonlinear distortion requires that SFOAE phase be essentially independent of frequency, in striking contradiction with experiment. This contradiction implies that evoked otoacoustic emissions arise by two fundamentally different mechanisms within the cochlea. These two mechanisms (linear reflection versus nonlinear distortion) are described and two broad classes of emissions--reflection-source and distortion source emissions--are distinguished based on the mechanisms of their generation. The implications of this OAE taxonomy for the measurement, interpretation, and clinical use of otoacoustic emissions as noninvasive probes of cochlear function are discussed. PMID- 9972565 TI - Response phase: a view from the inner hair cell. AB - Inner hair cell (IHC) responses are recorded from the apical three turns of the guinea pig cochlea in order to define the relationship between hair cell depolarization and position of the basilar membrane. At low frequencies, inner hair cell depolarization is generally observed near basilar membrane velocity to scala vestibuli, reflecting the putative freestanding nature of the IHC's stereocilia. While this is consistent with previous IHC results, independent of location, and with neural responses for fibers with low best frequencies, it is inconsistent with single-unit results from the base of the cochlea, where response phase is associated with basilar membrane velocity to scala tympani. Results suggest that the temporal disparity between IHC and neural data from the base of the cochlea may relate to several factors that influence transmembrane voltage in IHCs. First, extracellular voltages (Ingvarsson, 1981; Sellick et al., 1982; Russell and Sellick, 1983) can potentially affect low- and high-frequency regions differently because electrical interactions are more likely in the base of the cochlea than in the apex (Dallos, 1983, 1985). Second, waveform distortion and kinetic properties associated with voltage-dependent ion channels in the IHC's basolateral membrane can both influence response phase by adding harmonic components and lagging the receptor potential by as much as 90 deg. Third, the velocity dependence of IHCs in the apex appears to extend to higher frequencies than the velocity dependence demonstrated for IHCs in the base of the cochlea. These features, which influence the timing of discharges in the auditory nerve, are compared and evaluated. PMID- 9972566 TI - Analog very large-scale integrated (VLSI) implementation of a model of amplitude modulation sensitivity in the auditory brainstem. AB - An analog very large-scale integrated (VLSI) implementation of a model of signal processing in the auditory brainstem is presented and evaluated. The implementation is based on a model of amplitude-modulation sensitivity in the central nucleus of the inferior colliculus (CNIC) previously described by Hewitt and Meddis [J. Acoust. Soc. Am. 95, 2145-2159 (1994)]. A single chip is used to implement the three processing stages of the model; the inner-hair cell (IHC), cochlear nucleus sustained-chopper, and CNIC coincidence-detection stages. The chip incorporates two new circuits: an IHC circuit and a neuron circuit. The input to the chip is taken from a "silicon cochlea" consisting of a cascade of filters that simulate basilar membrane mechanical frequency selectivity. The chip which contains 142 neurons was evaluated using amplitude-modulated pure tones. Individual cells in the CNIC stage demonstrate bandpass rate-modulation responses using these stimuli. The frequency of modulation is represented spatially in an array of these cells as the location of the cell generating the highest rate of action potentials. The chip processes acoustic signals in real time and demonstrates the feasibility of using analog VLSI to build and test auditory models that use large numbers of component neurons. PMID- 9972567 TI - Masker laterality and cueing in forward-masked intensity discrimination. AB - Forward-masked intensity discrimination was measured as a function of level in experiments designed to reveal insights into the mechanism(s) underlying the midlevel elevation of the Weber fraction. The standard and maskers were 1.0-kHz tones that were separated by 100 ms. Performance was measured for listeners with normal hearing using an adaptive procedure. In experiment 1, intensity discrimination was measured in the presence of an ipsilateral masker (80 dB SPL), a contralateral masker (93 dB SPL), and a binaural (dichotic) masker produced by combining the ipsilateral and contralateral maskers. Listeners perceived only the contralateral masker in the binaural-masker condition. The contralateral masker produced a small midlevel elevation of the Weber fraction. The ipsilateral masker and the binaural masker produced a large, midlevel elevation of the Weber fraction. Experiment 2 found that a two-tone masker resulted in a reduction (improvement) in the Weber fraction for some conditions, but the midlevel elevation remained for all subjects in this cue-tone condition. Experiment 3 demonstrated that cross talk could not account for all of the masking observed with contralateral maskers. Taken together, the results suggest that a single complex mechanism or multiple mechanisms may be responsible for the masking seen in these experiments. On the basis of the cueing results, it is concluded that a portion of the masking is due to cognitive factors; however, a sensory mechanism cannot be ruled out for the remaining portion, based on the results of these experiments. Finally, a small but significant amount of masking due to contralateral maskers places the mechanism for this outcome central to the cochlear nucleus. PMID- 9972568 TI - Amplitude-modulation detection at low- and high-audio frequencies. AB - Estimates of temporal acuity under comparable conditions at low- and high-audio frequencies are rare. The present study used the amplitude-modulation detection paradigm to estimate temporal acuity over a range of audio frequencies from 800 to 12,800 Hz. Amplitude-modulation detection was measured as a function of modulation frequency for bandlimited noise carriers, and the resulting temporal modulation-transfer functions were used to characterize temporal acuity. The most important result from the two experiments reported is that systematic manipulations of carrier upper-cutoff frequency produced estimates of temporal acuity that did not vary from 800 to 12,800 Hz. When the modulated noise bands were filtered after modulation to control for potential spectral cues, the low pass cutoff of the modulation-transfer function varied with the carrier bandwidth. However, when the standard stimulus was a quasifrequency-modulated (QFM) noise and the signal was an unfiltered, amplitude-modulated noise, the low pass cutoff of the modulation-transfer function was independent of carrier bandwidth. These results are consistent with a growing body of evidence demonstrating that auditory temporal acuity is constant throughout most of the audible frequency range. PMID- 9972569 TI - Some aspects of the lateralization of echoed sound in man. II. The role of the stimulus spectrum. AB - The lateralization of clicks and their "echoes" was investigated with a view to determining the role of spectral characteristics in lateralization. Lateralization-discrimination performance was measured in a number of two interval, two-alternative forced-choice experiments using three pairs of binaural clicks designed to elucidate how spectral cues are used in lateralization. The stimulus in one observation interval comprised a diotic click followed, after the interclick interval (ICI), by a dichotic click with either (1) an interaural time delay or (2) an interaural amplitude difference. The dichotic click was in turn followed, after an ICI of the same size, by another diotic click. In the second observation interval, the signals to the two ears were interchanged. The stimulus has the property that the signals delivered to the two ears had either (1) identical energy-density spectra but nonzero interaural-phase differences (IPDs) or (2) zero IPDs but nonidentical energy-density spectra. Under certain circumstances, observers perceived these stimuli as arising from the side of the head opposite that which would be predicted from the direction of the interaural cue in the temporal waveform. Joint consideration of the psychophysical data and the spectral characteristics of the stimuli strongly suggest a spectral "dominance region" for lateralization near 750 Hz, observers' lateralization performance was determined predominantly by the IPD cues from this region. In general, the results demonstrate that echoes of transients that arrive within about 2-3 ms of an initial transient are not suppressed, but have a substantial effect on lateralization through their contribution to the resultant spectral characteristics. The results contradict models that represent the precedence effect as the temporary suppression or inhibition of directional information in echoes over 2-3 ms after an initial transient. PMID- 9972570 TI - Effects of stimulation mode on threshold and loudness growth in multielectrode cochlear implants. AB - The effect of increasing the separation between the two members of a stimulating electrode pair was studied in four users of the Nucleus-22 cochlear implant. Two experiments were performed. In experiment 1, detection threshold for a 200-ms, 500-pulses/s biphasic pulse train was measured as the spatial separation between the active and return electrodes was increased. In experiment 2, loudness-growth functions were measured as the electrode separation was increased. The results of experiment 1 indicate that (a) threshold decreases monotonically toward an asymptote (monopolar threshold) as the electrode separation is increased and (b) the threshold versus electrode separation function is similar across subjects and electrode location. The results of experiment 2 indicate that loudness L is related to the current amplitude I by a simple exponential function: L = e beta I, where beta, the exponent of the loudness function, is, to a first approximation, linearly related to the separation between the electrodes of the stimulating pair. Thus, dynamic range and the shape of loudness growth can be directly linked to the spatial separation between active and return electrodes. PMID- 9972571 TI - Investigation of the effects of temporal and spatial interactions on speech recognition skills in cochlear-implant subjects. AB - Forward masking was investigated as a measure of spectral and temporal interactions. Such interactions may adversely affect speech recognition in cochlear-implant subjects. Seven subjects, implanted with the Nucleus 22 device, performed a forward-masking task. They also performed an electrode-discrimination task in order to measure spectral interactions without temporal interactions. Correlation analysis indicated a significant relationship between data obtained in the two tasks (p < 0.1). The two tasks were also correlated with the subjects' scores from five measures of speech recognition. Forward masking and electrode discrimination were strongly correlated with measures requiring consonant and phoneme recognition, respectively. These results indicate that the relationship between forward masking and speech recognition may be due, in part, to a lack of spectral resolution. The data also indicate that consonants may be more readily masked than vowels. Forward-masking data measured for all clinically programmed electrodes in three of the seven subjects were used with a model of the spectral maxima sound processor (SMSP) to estimate the number of electrodes stimulated during a consonant that might be masked by prior presentation of a vowel. These results suggest that temporal interactions across electrodes may be a factor in speech-recognition abilities of some cochlear-implant subjects. PMID- 9972572 TI - Blowing pressure, power, and spectrum in trumpet playing. AB - Measurements of sound output as a function of blowing pressure are reported for a group of experienced trumpet players. The study identifies several common features, namely (1) a threshold blowing pressure approximately proportional to the frequency of the note being played, (2) an extended region in which the sound output rises by about 15 dB for each doubling of blowing pressure, and (3) a saturation region in which sound output rises by only about 3 dB for a doubling of blowing pressure. Some players are able to blow with maximum pressures as high as 25 kPa, which is significantly greater than normal systolic blood pressure. A simple theory is presented that provides a physical explanation for the acoustical behavior, but a detailed treatment requires solution of the nonlinear coupled equations both for the lip-valve mechanism and for nonlinear wave propagation in the instrument tube. Frequency analysis of the sound shows a basic spectral envelope determined by the resonance properties of the mouthpiece cup and the radiation behavior of the bell, supplemented by an extension to increasingly high frequencies as the blowing pressure is increased. This high frequency behavior can be attributed to nonlinear wavefront steepening during sound propagation along the cylindrical bore of the instrument. PMID- 9972573 TI - Discrimination of musical instrument sounds resynthesized with simplified spectrotemporal parameters. AB - The perceptual salience of several outstanding features of quasiharmonic, time variant spectra was investigated in musical instrument sounds. Spectral analyses of sounds from seven musical instruments (clarinet, flute, oboe, trumpet, violin, harpsichord, and marimba) produced time-varying harmonic amplitude and frequency data. Six basic data simplifications and five combinations of them were applied to the reference tones: amplitude-variation smoothing, coherent variation of amplitudes over time, spectral-envelope smoothing, forced harmonic-frequency variation, frequency-variation smoothing, and harmonic-frequency flattening. Listeners were asked to discriminate sounds resynthesized with simplified data from reference sounds resynthesized with the full data. Averaged over the seven instruments, the discrimination was very good for spectral envelope smoothing and amplitude envelope coherence, but was moderate to poor in decreasing order for forced harmonic frequency variation, frequency variation smoothing, frequency flattening, and amplitude variation smoothing. Discrimination of combinations of simplifications was equivalent to that of the most potent constituent simplification. Objective measurements were made on the spectral data for harmonic amplitude, harmonic frequency, and spectral centroid changes resulting from simplifications. These measures were found to correlate well with discrimination results, indicating that listeners have access to a relatively fine-grained sensory representation of musical instrument sounds. PMID- 9972574 TI - Perception of complex tones and its analogy to echo spectral analysis in the bat, Megaderma lyra. AB - The gleaning bat Megaderma lyra emits broadband echolocation sounds consisting of multiple frequency components. The present study investigates into which perceptual qualities the spectral characteristics of echoes may be translated in the auditory system of M. lyra. Three bats were trained in a 2-AFC behavioral experiment to classify nine complex tones, which spectrally resembled M. lyra's sonar calls, into two perceptual categories. Then the bats' spontaneous responses to unknown complex tones were recorded. The results show that the animals based their classifications of the complex tones on a sound quality which was mediated by their broadband frequency spectra. The bats used the training stimuli as spectral templates and classified the test stimuli according to their broadband spectral similarity with the learned patterns. Assuming that passive hearing and echo processing are governed by similar perceptual qualities and subject to similar limitations, the perceptual mode which was used by the bats to compare the multicomponent spectral patterns in the reported experiments could serve as a powerful tool for the spectral analysis of M. lyra's multicomponent echoes. The analogy between the perception of complex tones and echo spectral analysis in M. lyra is theoretically elaborated in the "formant-mode" model. PMID- 9972575 TI - Comment on "Enhancement of the transient-evoked otoacoustic emission produced by the addition of a pure tone in the guinea pig" [J. Acoust. Soc. Am. 104, 344-349 (1998)]. PMID- 9972576 TI - Comments on "An approach for modeling noncancer dose responses with an emphasis on uncertainty" and "A probabilistic framework for the Reference Dose (probabilistic RfD)". PMID- 9972577 TI - Target levels--tools for prevention. AB - Although occupational exposure limits are sought to establish health-based standards, they do not always give a sufficient basis for planning an indoor air climate that is good and comfortable for the occupants in industrial work rooms. This paper considers methodologies by which the desired level, i.e., target level, of air quality in industrial settings can be defined, taking into account feasibility issues. Risk assessment based on health criteria is compared with risk-assessment based on "Best Available Technology" (BAT). Because health-based risk estimates at low concentration regions are rather inaccurate, the technology based approach is emphasized. The technological approach is based on information on the prevailing concentrations in industrial work environments and the benchmark air quality attained with the best achievable technology. The prevailing contaminant concentrations are obtained from a contaminant exposure databank, and the benchmark air quality by field measurements in industrial work rooms equipped with advanced ventilation and production technology. As an example, the target level assessment has been applied to formaldehyde, total inorganic dust and hexavalent chromium, which are common contaminants in work room air. PMID- 9972578 TI - Information and risk perception: a dynamic adjustment process. AB - It is common in catastrophic food-contamination events that consumers fail to adjust instantaneously to a normal consumption level. One explanation is that consumers only gradually accept new positive information as being trustworthy. The gradual establishment of the trustworthiness of the released information depends on both positive and negative media coverage over time. We examine the individual "trust" effects by extending the prospective reference theory (Viscusi, 1989) to include a dynamic adjustment process of risk perception. Conditions that allow aggregation of changes in risk perceptions across individuals are described. The proposed model describes a general updating process of risk perceptions to media coverage and can be applied to explain the temporal impact of media coverage on consumption of a broad range of goods (food or nonfood). A case study of milk contamination is conducted to demonstrate consumer demand adjustment process to a temporarily unfavorable shock. The results suggest that effects of positive and negative information to adjustment of consumption and risk perception are asymmetric over time. PMID- 9972579 TI - Influence of prenatal mercury exposure upon scholastic and psychological test performance: benchmark analysis of a New Zealand cohort. AB - This paper presents benchmark (BMD) calculations and additional regression analyses of data from a study in which scores from 26 scholastic and psychological tests administered to 237 6- and 7-year-old New Zealand children were correlated with the mercury concentration in their mothers' hair during pregnancy. The original analyses of five test scores found an association between high prenatal mercury exposure and decreased test performance, using category variables for mercury exposure. Our regression analyses, which utilized the actual hair mercury level, did not find significant associations between mercury and children's test scores. However, this finding was highly influenced by a single child whose mother's mercury hair level (86 mg/kg) was more than four times that of any other mother. When that child was omitted, results were more indicative of a mercury effect and scores on six tests were significantly associated with the mothers' hair mercury level. BMDs calculated from five tests ranged from 32 to 73 mg/kg hair mercury, and corresponding BMDLs (95% lower limits on BMDs) ranged from 17 to 24 mg/kg. When the child with the highest mercury level was omitted, BMDs ranged from 13 to 21 mg/kg, and corresponding BMDLs ranged from 7.4 to 10 mg/kg. PMID- 9972582 TI - A probabilistic approach for deriving acceptable human intake limits and human health risks from toxicological studies: general framework. AB - The use of uncertainty factors in the standard method for deriving acceptable intake or exposure limits for humans, such as the Reference Dose (RfD), may be viewed as a conservative method of taking various uncertainties into account. As an obvious alternative, the use of uncertainty distributions instead of uncertainty factors is gaining attention. This paper presents a comprehensive discussion of a general framework that quantifies both the uncertainties in the no-adverse-effect level in the animal (using a benchmark-like approach) and the uncertainties in the various extrapolation steps involved (using uncertainty distributions). This approach results in an uncertainty distribution for the no adverse-effect level in the sensitive human subpopulation, reflecting the overall scientific uncertainty associated with that level. A lower percentile of this distribution may be regarded as an acceptable exposure limit (e.g., RfD) that takes account of the various uncertainties in a nonconservative fashion. The same methodology may also be used as a tool to derive a distribution for possible human health effects at a given exposure level. We argue that in a probabilistic approach the uncertainty in the estimated no-adverse-effect-level in the animal should be explicitly taken into account. Not only in this source of uncertainty too large to be ignored, it also has repercussions for the quantification of the other uncertainty distributions. PMID- 9972581 TI - Empirical scaling of single oral lethal doses across mammalian species based on a large database. AB - The scaling of administered doses to achieve equal degrees of toxic effect in different species has been relatively poorly examined for noncancer toxicity, either empirically or theoretically. We investigate empirical patterns in the correspondence of single oral dose LD50 values across several mammalian species for a large number of chemicals based on data reported in the RTECS database maintained by the National Institute for Occupational Safety and Health. We find a good correspondence of LD50 values across species when the dose levels are expressed in terms of mg administered per kg of body mass. Our findings contrast with earlier analyses that support scaling doses by the 3/4-power of body mass to achieve equal subacute toxicity of antineoplastic agents. We suggest that, especially for severe toxicity, single- and repeated-dosing regimes may have different cross-species scaling properties, as they may depend on standing levels of defenses and rate of regeneration of defenses, respectively. PMID- 9972583 TI - Gender differences in risk perception: theoretical and methodological perspectives. AB - A substantial body of risk research indicates that women and men differ in their perceptions of risk. This paper discusses how they differ and why. A review of a number of existing empirical studies of risk perception points at several problems, regarding what gender differences are found in such studies, and how these differences are accounted for. Firstly, quantitative approaches, which have so far dominated risk research, and qualitative approaches give different, sometimes even contradictory images of women's and men's perceptions of risk. Secondly, the gender differences that appear are often left unexplained, and even when explanations are suggested, these are seldom related to gender research and gender theory in any systematic way. This paper argues that a coherent, theoretically informed gender perspective on risk is needed to improve the understanding of women's and men's risk perceptions. An analysis of social theories of gender points out some relations and distinctions which should be considered in such a perspective. It is argued that gender structures, reflected in gendered ideology and gendered practice, give rise to systematic gender differences in the perception of risk. These gender differences may be of different kinds, and their investigation requires the use of qualitative as well as quantitative methods. In conclusion, the arguments about gender and risk perception are brought together in a theoretical model which might serve as a starting point for further research. PMID- 9972584 TI - Estimation of unit risk for coke oven emissions. AB - In 1984, based on epidemiological data on cohorts of coke oven workers, USEPA estimated a unit risk for lung cancer associated with continuous exposure from birth to 1 microgram/m3 of coke oven emissions, of 6.2 x 10(-4). This risk assessment was based on information on the cohorts available through 1966. Follow up of these cohorts has now been extended to 1982 and, moreover, individual job histories, which were not available in 1984, have been constructed. In this study, lung cancer mortality in these cohorts of coke oven workers with extended follow-up was analyzed using standard techniques of survival analysis and a new approach based on the two stage clonal expansion model of carcinogenesis. The latter approach allows the explicit consideration of detailed patterns of exposure of each individual in the cohort. The analyses used the extended follow up data through 1982 and the detailed job histories now available. Based on these analyses, the best estimate of unit risk is 1.5 x 10(-4) with 95% confidence interval = 1.2 x 10(-4)-1.8 x 10(-4). PMID- 9972585 TI - [Separation anxiety and panic disorder]. AB - History od separation anxiety was investigated in several psychiatryc disorders and in 150 patients with panic disorder following DSM III-R criteria. Separation anxiety was reported by 15.3% of patients with panic disorder, 3.3% of the healthy control group, 13.3% of patients with major depression, 16.7% with dystymia, 13.3% with generalized anxiety and 33.3% with social phobia (p < 0.001). Separation anxiety is thus considered a common predisposing factor of anxiety and depressive disorders. Panic disorder patients with a history of separation anxiety had an earlier age at panic onset and greater comorbidity with social phobia and agoraphobia. PMID- 9972586 TI - [Comparative naturalistic study of the efficacy and tolerability of new antidepressants]. AB - OBJECTIVES: The objective of this study was to compare, in a naturalistic setting, the efficacy and tolerability of currently available Selective Serotonin Re-uptake Inhibitors (SSRIs) and venlafaxine in out-patients from a primary psychiatric-care center. MATERIAL AND METHODS: The sample was composed of 194 patients with mood disorders (major depressive disorder or dysthymic disorder according to the DSM-IV criteria) who initiated treatment either with a SSRI (fluoxetine, fluvoxamine, paroxetine, sertraline, and citalopram) or with venlafaxine. Baseline severity of the mood disorder was assessed using the Hamilton Depression Rating Scale and State-Trait Anxiety Inventory, and therapeutic response was measured with the Clinical Global Impression for Therapeutic Improvement. Tolerability was assessed by recording spontaneously reported adverse experiences. Patients were followed up for six months, with subjects made three o more intermediate visits. RESULTS: There were no significant differences in the efficacy of the antidepressants under study, but there were differences in the incidence and profiles of adverse events. Fluoxetine was associated with the lowest incidence of adverse effects in a logistical regression model. Particular events seemed to be associated with certain treatments; gastrointestinal discomfort (fluvoxamine), tremor (sertraline) and anticholinergic effects (venlafaxine). PMID- 9972587 TI - [Assessment of clinical assessment reliability among researchers of a multicenter clinical trial]. AB - INTRODUCTION: Interater agreement is a main aspect in the planning and conducting a clinical trial. The objective of this study is to show the application of assessing levels of interexaminer's agreement when multiple ratings are made on a single subject as an efficient method of evaluating the interater's reliability in planning a multicenter clinical trial. METHOD: 39 psychiatrist assessed videotape of a patient with depression. The use of any reliability statistics is failed in the analysis of multiple independent ratings of a single subject since we used the methodology proposed by Cichetti et al. This method is able to identify raters whose ratings differ significantly from the average ratings and is sensitive for different levels of agreement. RESULTS: Interarter agreement was between good and excellent. The raters show an adequate agreement in total and items scores. CONCLUSION: The design proposed permits evaluate the interater agreement in an efficient way (only in one session). PMID- 9972588 TI - [Normative data for the neuropsychological evaluation of intravenous drug users]. AB - BACKGROUND: There are many recent epidemiological studies that find that intravenous drug users' (IDU's) performance in several measures of neuropsychological function are not the same than that of the general population, whether they are seropositive to HIV-1 infection or not. Consequently, it has been stated the need to establish appropriate norms for this population. The purpose of this study is to provide normative data on a battery of neuropsychological tests from a IDU group. SUBJECTS AND METHODS: This report provide normative data from a group of 116 IDU, on a battery of neuropsychological tests stratified by age group (mean = 30.9; SD = 4.5), and educational level (mean = 8; SD = 2.4). Comparisons between the means of the different groups according to age and education, and also with respect to sex are made. The analysis includes estimation of partial correlations between neuropsychological test scores and age and education. RESULTS: The analysis demonstrates that education is an important determinant of performance for most of these tests, while there are no differences in performance between the two age groups. With respect to sex, females out-performed men on a measure of motor speed and coordination. CONCLUSIONS: This report provides norms that may be of use as a reference for clinical evaluation and research in drug user populations. It also emphasizes the need to establish normative data controlling for variables like educational level, from a population with special characteristics such as IDU population. PMID- 9972589 TI - [Benzodiazepines in the treatment of schizophrenia: a review]. AB - Since the introduction of benzodiacepines in the medical practice their use has been generalized to numerous clinical situations. One of them is schizophrenia. In this article we analize the main settings for its use and the possible mechanisms of action, trying to draw some recomendations applicable to the psychiatric practice. PMID- 9972591 TI - [Importance of the early diagnosis of malignant neuroleptic syndrome: report of 2 cases]. AB - Two cases of neuroleptic malignant syndrome presented in a psychiatry inpatient unit are commented, as well as their positive evolution. PMID- 9972590 TI - [Apolipoproteins and cognitive deterioration]. AB - Main studies which have shown an association between the variation in apolipoprotein genes and human neuropsychological impairement are reviewed in this work. Data from literature indicate a special relevance of apolipoprotein E (ApoE) in relation to Central Nervous System (CNS) functions, basically memory. ApoE epsilon 4 is a well documented risk factor for late-onset Alzheimer's Disease (AD). Memory changes in older adults and in AD are also associated with ApoE genotype. Furthermore, ApoE may play a role in formation or degeneration of some neural structures related to memory. In some studies a relation between ApoE's alleles and cerebral vascular disorders like ischemic, haemorrhagic, Vascular (VD) and Multi-infarct (MD) Dementias is also reported. The role of the remaining apolipoproteins in cognitive impairment is still unknown, and these molecules have been considered as risk factors associated with environmental factors in CNS pathologies, essentially the vascular ones. PMID- 9972592 TI - [Psychiatric symptoms in Cushing syndrome: a clinical case]. AB - A patient with Cushing's syndrome presented psyquiatric manifestations that were diagnosed and treated before diagnosis of Cushing's syndrome. These manifestations were unspecific, unstable and they responded to etiologic treatment but they didn't to syntomatic treatment. This case demonstrates the importance to make a through search for organic factors when there are changes in physical appearance and psyquiatric features are changing through the evolution. PMID- 9972593 TI - [Combination of risperidone and serotonergic antidepressants in refractory obsessive-compulsive disorder]. AB - We present the use of risperidone as a potentiation strategy of the serotonergic antidepressants in four patients suffering from refractory obsessive-compulsive disorder. There were an important improvement in three patients. Adding risperidone to serotonergic antidepressants causes complex interactions between serotonergic, dopaminergic and noradrenergic systems, that could lay to the clinical improvement. These and other similar cases make necessary controlled studies. Adding risperidone to serotonergic antidepressants in patients suffering from refractory obsessive-compulsive disorder might be an effective strategy with low risk for secondary effects and without the presence of tics or psychotic symptoms. PMID- 9972594 TI - [Nutritional status of patients with HIV-AIDS infection]. PMID- 9972595 TI - [Evolution of the nutritional status of patients with HIV-AIDS. Effects of socioeconomic situation and dietetic counseling]. AB - OBJECTIVES: To know HIV-AIDS patient's nutritional status in different infection's condition and their relation with the socioeconomic situation and, in that case, the nutritional condition improvement through the dietetic advice appropriated for each patient. METHODS: Prospective study of 79 patients with HIV AIDS diagnostic in any illness's condition and recopilation of anthropometrics and biochemical variables. At the beginning of the study we got data about socioeconomic situation of patient with a scale of 1 to 5 points each variable and an score top of 35. In the survivors we checked, after dietetic advice, the variables at 6 and 12 months by sanitary personal (physician and nurse) who weren't implicated in direct assistance. The study was analyzed by Student "T" for matched data and the simple correlation test. RESULTS: We have objectivated a lost of initial weight over their habitual's with a progressive impairment in different stage of evolution that weren't modified by dietetic advice. We didn't observed significant variations in the biochemical variables included in advances states and in parameters which are usually affected in malnutrition. In the analysis of relation between nutritional condition and socioeconomic factors, it was estimated a lesser score, that was statistically significative, in patients who had a work, family situation and an affective upset positive. CONCLUSIONS: The results obtained induce to think that the nutritional advices appropriated for each patient are not related, in our series, with progressive deterioration of anthropometrics variables, neither biochemical parameters fluctuations at 6, 12 months of follow-up. The patient's socioeconomic situation is not influenced by nutritional condition except for the work, affectivity and family environment. PMID- 9972596 TI - [Impact of HIV infection in hospital environment]. AB - OBJECTIVE: Retrospective study to review the admissions at the Hospital Marina Alta due to infection for HIV or its complications and look for risk factors. METHODS: Clinical charts of patients admitted at the hospital from 1989 to 1996 were analyzed. RESULTS: From 11,932 admissions, 199 (1.7%) were due to patients with infection from HIV, resulting in the 2.4% of the total stay. The medium stays were higher (8.6 +/- 7.4 vs 6 +/- 4.5) more re-admissions (42.7% vs 25.5%) and higher mortality (11% vs 7.8%). The parasitic infestations of the nervous central system and cardiovascular were the most numerous number of admissions and also the longer stays. Throughout the years we saw a increase in the patients at the outpatient clinic with HIV infection and a paradogic decrease in the inpatient admissions, and also a decrease in the media stay and total stays. CONCLUSIONS: There is a decrease in the admissions at the inpatient level in contrast with a increment of the prevalence in the outpatients with HIV infection. The improved treatments, the experience of the physicians, the use of the Day Hospital and the use of the service of Home Care Hospitalization allows to keep more patients with less admissions and more outpatient visits. PMID- 9972597 TI - [Study of histoenzymatic activity of isocitrate-DH in the hepatic tissue of rats treated with AZT: image analysis]. AB - OBJECTIVE: Recently has been described alterations in different organs of HIV + patients treated with zidovudine (AZT), as secondary effect from drug administration. METHOD: We have developed and experimental rat model, in which the rats were administered AZT in drinking water and we have analysed the activity of enzyme isocitrate DH, of Krebs cycle, in hepatic tissue sections. Histological technique were employed and image analysis to objectivate the results. RESULTS: A significant statistic decrease of the enzyme activity in those animals treated with AZT were observed, compared with the control groups. CONCLUSIONS: The modification from enzyme activities related with Krebs cycle can be traduced in mitochondrial alterations, that could have direct or indirect influence in the appearance of some associated pathologies to the AZT treatment. PMID- 9972598 TI - [Epidemiological changes in infectious endocarditis. A prospective study, 1992 96]. AB - BACKGROUND: To know the present epidemiological situation of the infective endocarditis in our environment and its evolution in the last few years. RESULTS: The incidence of infective endocarditis was 0.85 per thousand patients admitted to hospital, with a mean age of 43 years. The predisposed factors more frequently found were: drug addiction (32%) and cardiac prosthetic valves (23%). In the greatest number of our patients the cardiac valves involved were: tricuspid (28%), mitral (27%) and prosthetic valves (23%). The causative organism were: S. aureus (19 cases), Streptococcus (15 cases) and S. epidermidis (11 cases). The echocardiography study resulted diagnostic in 90% of the patients, valve replacements were performed in 22% of the cases. The overall mortality rate was 10%. CONCLUSIONS: The current profile of infective endocarditis is characterized by a high incidence of parenterally drug addict patients or prosthetic valves carriers. Increase of the infections of S aureus and a decrease of Streptococcus infections, as well as a less overall mortality. PMID- 9972599 TI - [Value of quantification of p24 antigen in plasma as a prognostic marker of survival in a cohort of 251 HIV-positive patients]. AB - OBJECTIVE: To analyse plasma p24 antigen as a marker of survival in a cohort of HIV-infected patients whose time of seroconversion is unknown. DESIGN: Prospective cohort study. SETTING: AIDS Unit in a teaching hospital. PATIENTS: 251 patients were studied, most on antiretroviral therapy. Mean initial CD4 cell counts were 376 x 106/ 1 (range: 0.8-1350). 51 cases had been diagnosed previously with AIDS. METHODS: Analysis of survival, according to initial plasma p24 antigen was performed by Kaplan-Meier test. Relative risks were calculated by Cox's proportional hazards model. RESULTS: During a follow-up period of 24 months, 46 patients died. Relative risk (RR) of death related to the group with p24 antigen = < 40 pg/ml was 3.32 when p24 antigen > 40 pg/ml (p = 0.0001). CD4+ cell levels adjusting, the result was 2.47 (CI 95% 1.37-4.46) (p = 0.0027). CONCLUSIONS: Plasma levels of p24 antigen is useful as a marker of the risk of death and it behaves as a independent prognostic marker in our patients. P24 antigen = < 40 pg/ml is associated with a better prognosis. PMID- 9972600 TI - [Mucocutaneous manifestations in acute HIV infection. 3 case reports]. AB - We report three patients who developed a generalized rash with oral, genital or perianal ulcerations as a result of acute infection due to HIV. The primary infection was diagnosed by seroconversion (by means of EIA and Western blot techniques). Definitive diagnosis was established on days 52, 85 and 97 after the appearance of the rash. The p24 protein of the HIV was only detected in the early phase of the disorder in the two cases in which this study was carried out. PMID- 9972601 TI - [Acute hepatic failure and Hodgkin's disease]. AB - We present the clinical outcome and imaging micro and macroscopic of a patient who died of e liver acute failure. Hodgkin disease with massive infiltration was found at necropsy. We offer a review of the liver complaint in this particular disease. PMID- 9972602 TI - [Dilatation of the azygos vein: an unusual cause of pulmonary mass]. AB - Infrahepatic interruption of the inferior cava vein, is a rare congenital anomaly, usually associated with congenital heart and abdominal diseases. The systemic venous flow is accommodated by the dilated azygos. This dilated azygos arch accounts for the right paratracheal or mediastinal mass, and may be misinterpreted as a neoplasm. We report a case with this congenital vascular anomaly, associated with another of tracheobronchial tree. PMID- 9972603 TI - [Central diabetes insipidus secondary to infundibuloneurohypophysitis]. AB - In up to a third of cases, central diabetes insipidus (DIC) is idiopathic although the percentage varies in different series. Since antibodies against magnicellular neurons were detected in some patients, a possible autoimmune basis for certain cases of apparently idiopathic DIC was speculated. Lymphocytic infundibuloneurohypophysitis, an inflammatory process that affects the infundibulum, pituitary stalk and neurohypophysis with distinctive radiologic, histologic and evolutive characteristics, has recently been described as a cause of central diabetes insipidus. We describe a patient in whom the clinical and radiologic characteristics suggest the diagnosis of DIC secondary to infundibuloneurohyphysitis. PMID- 9972604 TI - [Alveolar hemorrhage in mixed cryoglobulinemia associated with hepatitis C virus infection]. AB - Alveolar hemorrhage in mixed cryoglobulinemia associated with hepatitis C virus infection. A 61 year-old woman with type II mixed cryoglobulinemia associated to hepatitis C virus infection has suffered alveolar hemorrhage with multiple pulmonary infiltrates, purpura, glomerulonephritis and polyneuropathy. The respiratory and kidney findings resolved with prednisone, but glomerulonephritis reappeared when interferon-alpha treatment was started and prednisone was reduced. This is the third case of alveolar hemorrhage and glomerulonephritis associated with mixed cryoglobulinemia reported in the literature. The lung involvement in mixed cryoglobulinemia is reviewed. The clinic manifestations (asthma, pleural effusion, hemoptysis or pulmonary fibrosis) are uncommon, but the lung involvement is very frequent if roentgenographic signs and necropsy findings are assessed. PMID- 9972605 TI - [Evaluation of new programs to prevent tuberculosis infection. I. Chemoprophylaxis]. AB - Tuberculosis is an infectious disease produced by Mycobacterium tuberculosis in a 98-99% of the cases and by Mycobacterium bovis in a 1-2%. Its early diagnosis is of a great importance because permits to reduce the transmission of the infection. Until now, the diagnostic techniques used to discover the dissemination of the disease are indirect. We have the PPD skin test and, among them, Mantoux is the most common. Correctly used it has a great diagnostic and epidemiological value, because it permits to evaluate those patients who can obtain a benefit with the chemoprophylaxis when the skin test is positive. We analyse the actual via of chemoprophylaxis, when and how it must be used. We study not only the drugs for the prophylaxis, but also the good and bad utilisation of the BCG vaccine, that it starts to have its indications in other countries. PMID- 9972606 TI - [Snoring and vascular diseases]. AB - The aim of this study is to review the evidence linking snoring with vascular disease. This has been a topic of numerous investigations with divergent results, mainly because of the differences in methodology employed in various studies, such as inclusion of confounding factors, methods of measures, etc. While some studies shows that snoring is a risk factor for vascular disease, another reached the opposite conclusion. Consequently, based on the available information, it s very difficult to conclude that snoring is an independent risk factor for vascular complications as hypertension and cardiovascular and cerebrovascular disease. PMID- 9972607 TI - [Pulmonary cryptosporidiosis and AIDS]. PMID- 9972608 TI - [Stroke in young adults]. PMID- 9972609 TI - [A new case of localized Castleman's disease]. PMID- 9972610 TI - [Inappropriate admissions to the Department of Internal Medicine evaluated by the AEP (Appropriateness Evaluation Protocol)]. PMID- 9972611 TI - [Treatment of idiopathic thrombopenic purpura in adolescents by intravenous immunoglobulin]. PMID- 9972612 TI - [Yohimbine-induced angina pectoris]. PMID- 9972613 TI - [Subacute lupus erythematosus evolving to systemic lupus erythematosus during pregnancy]. PMID- 9972614 TI - [Hepatitis B vaccine and multiple sclerosis]. PMID- 9972615 TI - [Recent advances in the knowledge of energy homeostasis]. PMID- 9972616 TI - [Leptin and puberty]. PMID- 9972617 TI - [The coverage of vaccines systematically administered and of a vaccine against Haemophilus influenzae type b prior to its inclusion in the vaccinal calendar in the Valencian Community]. AB - OBJECTIVE: The objective of this study was to estimate the vaccine coverage among children two years of age in the Community of Valencia, Spain, in 1997. PATIENTS AND METHODS: Cluster sampling was used to assess vaccine coverage. Clusters were villages randomized according to their population < 5 years of age. At least 7 children of each of the 30 selected clusters were randomly selected from the database of newborn metabolic screening. Parents were contacted and vaccine registration cards requested by mail. RESULTS: Four hundred forty subjects were selected. Eight percent of the families had moved and were not contacted. Sixty nine percent participated in the study. Coverage for three doses of DTP was 97.8% and 87.6% for four doses. MMR vaccine coverage was 96.6% and three doses of hepatitis B had been given in 95.1%. H. influenzae type b (Hib) vaccine coverage was 57%. In 70% of the studied cases of non-participants, vaccine coverage was known through vaccination centers and was very similar to that of the participants. CONCLUSIONS: Vaccine coverage in the Community of Valencia is high for the scheduled vaccines. Although Hib is not a scheduled vaccination, its coverage was 57%. PMID- 9972618 TI - [A radiological assessment of the nasopharynx in healthy children from the Madrid area]. AB - OBJECTIVE: The objective of this study was to assess the adenoid size of each pediatric age group in our media and to compare the subjective visual assessment with a confronted measurement, the Fujioka's adenoidal-nasopharyngeal (AN) ratio. These data would allow the composition of a map, a guide for pediatricians useful in predicting the degree of upper airway obstruction, the role of adenoids in the etiology of serious otitis media and/or in selecting patients for adenoidectomy. PATIENTS AND METHODS: We studied 1,033 radiographs of the nasopharynx taken in the emergency room of children between 5 months and 15 years of age that did not have any otorhinolaryngological (ENT) pathology. These individuals had no history of ear, nose or throat disease and the ENT evaluation was done in order to discard any ENT pathology. The subjective review and the AN ratios were calculated by experienced observers, tabulated and statistically analyzed. RESULTS: Only 692 infants and children passed the careful selection. The differences in mean values among the ages were statistically significant (p < 0.001). The mean AN ratio reached its highest value (0.575) at 5 years of age. The AN ratio as an indicator of adenoid size was comparable to the visually estimated classifications of adenoid size (p < 0.0001). In addition, 85% of the radiographs selected were in the group normal to slightly enlarged (AN = 0.48). CONCLUSIONS: The distribution of the mean AN ratios for age groups in healthy children shows a line which we could use as a standard, or guideline, to compare the AN ratio of any infant or child with any pathology related to the adenoids. PMID- 9972619 TI - [Recent changes in emergency room visits and hospitalization for asthma in childhood]. AB - OBJECTIVE: The purpose of this study was to investigate recent changes in the emergency room visits and hospital admission rates between 1993 and 1997 in our hospital. PATIENTS AND METHODS: From January 1, 1993 until December 31, 1997, the 12,848 patients between 0 and 14 years of age whose discharge diagnosis was coded as asthma (ICD9) and who were managed in the emergency room of our hospital were included in the study. RESULTS: During the study period, the number of emergency room visits for asthma (EA) remained unchanged. However, in children between 0 and 5 years of age the number of EA showed a significant increase from 1305 in 1993 (53.5% of all EA) to 1849 in 1997 (68.9% of EA), with an increase of the repeat visits in this age group from 46 (35.8% of all EA in this age group) in 1993 to 791 (42.8%) in 1997 (p < 0.01). In the same period of time, the admission rates for asthma decrease from 7.2% to 2.9% (p < 0.01). There was a trend towards more intense treatment of asthma in the emergency observation unit. CONCLUSIONS: There has been an upward trend in the number of acute asthma episodes between 1993 and 1997 in children between 0 and 5 years of age. It was associated with an increase in the number of repeat visits per patient. The use of a more intense treatment in the emergency observation unit was associated with a reduction in the hospitalization rate for asthma. PMID- 9972620 TI - [The middle lobe syndrome in pediatrics. A study of 27 cases]. AB - OBJECTIVE: The purpose of this study was to analyze the features, treatment and evolution of middle lobe syndrome (MLS) or atelectasis syndrome in children. PATIENTS AND METHODS: Between 1992 and 1996, all cases of MLS seen in our center by our staff were followed by using a prospective study protocol. RESULTS: Twenty seven patients were studied. The average age at the onset of MLS was 3 years 1 month +/- 2 years 4 months. Recurrent pneumonia was seen in 66.7% and 44.4% had asthma and/or elevated IgE. Acute symptoms at the onset were seen in 74% of the cases, with persistent cough being the most common symptom. Complementary procedures (chest X-rays, computed tomography scans, bronchoscopy, V/P scintigraphy) demonstrated 16 cases of pneumonia, 13 of atelectasis, 7 of bronchiectasia and 4 cases with other abnormalities. Infectious etiology was the most predominant (66.7%) Bronchoscopy was performed in 8 cases and 5 of them improved immediately. Pulmonary scintigraphy was normal in those patients with radiographic residual images. All patients were initially medically treated. Three were lobectomized. Twenty-three patients healed. The younger the patient at the onset of MLS the better the cure rate. CONCLUSIONS: Infectious causes were dominant in our series. Early and aggressive medical treatment may cure the majority of cases. Bronchoscopy is helpful in the diagnosis and as a therapeutic procedure. Scintigraphy could be helpful as a resolution criterion when there are residual radiographic images. PMID- 9972621 TI - [The opinion of pediatricians on childhood pain]. AB - OBJECTIVE: The objective of this study was to evaluate the current sensibility and knowledge of pediatricians regarding the issue of pediatric pain assessment and management. PATIENTS AND METHODS: In October 1996 we conducted a mail survey of all 686 members of the Asturias, Cantabria and Castilla y Leon Pediatric Society. Physicians were asked to complete and return a confidential 95-item questionnaire. RESULTS: One hundred fifty-seven (23%) of eligible physicians responded. Ninety percent of the respondents agreed they had insufficient training in pain management. Sixty-nine percent though their knowledge to deal with acute pain was adequate. Only 12% admitted to having enough background to treat chronic pain. Sixty-five percent of the respondents admitted to know no method at all for pain evaluation, while 82% had never applied any in their clinical practice. About half the respondents (42%) did not know any guidelines for the management of pediatric pain, although 75% considered they would be very useful. A high percentage of pediatricians answered that analgesia was required before performing certain diagnostic or therapeutic procedures (lumbar puncture, venous canalization, arterial puncture and others), but differences in relation to age, sex and clinical setting of the physicians were detected in these responses. The most used drug for the treatment of moderate acute pain is acetaminophen (88%), for severe acute pain metamizol (58%) and for severe chronic pain acetaminophen-codeine (37%). Only 48% admitted to having used opioids. CONCLUSIONS: Pediatricians in this society seem to be too confident about the topic of acute pain management in their patients, even though they report a lack of training which could influence the quality of the care they are offering to their patients. Opioid use is very low. Training in childhood pain management is needed. PMID- 9972622 TI - [Haemophilus influenzae type b osteoarthritis. A report of 7 cases and a review of the literature]. AB - OBJECTIVE: The epidemiological and clinical characteristics, treatment and evolution of osteoarthritis by Haemophilus influenzae type b (HIB) are reviewed since there has been little published on this subject in our country. PATIENTS AND METHODS: The clinical histories of the 7 children with osteoarthritis due to Hib infection are reviewed. The diagnostic criteria included classical signs and symptoms of septic arthritis, radiological alterations compatible with joint infection and isolation of microorganisms in joint effusion and/or in the blood. RESULTS: During a 24-year period (1973-1996), 248 cases of invasive infection by Hib were documented. Seven cases (2.82%) had osteoarticular infections. The ages were between 5 and 7 years and there were more males than females (71.4% vs. 28.6%). Four children/58%) had previous upper respiratory infections (URI). The microorganism was isolated in the joint effusion in 5 children and in the blood sample of the other 2. C-reactive protein was high and radiology showed alterations in 100% of the cases. Surgical treatment with articular drainage was necessary in 5 children/71.4%). In 6 cases (85.7%) initial medical treatment was i.v. beta-lactam antibiotics for 2-3 weeks followed by oral antibiotic treatment for a minimum of 6 weeks. Three children (42.8%) had sequelae. CONCLUSIONS: Early diagnosis of bacterial osteoarthritis by Hib is difficult. Final therapeutical success depends on an early clinical diagnosis and aggressive multidisciplinary treatment. Drainage of the hip joint is mandatory for successful outcome. Currently, arthritis by Hib can be avoided and its sequelae prevented by vaccination. PMID- 9972623 TI - [The treatment results in children diagnosed with non-Hodgkin's lymphomas and acute B-cell lymphoblastic leukemias treated by the BFM protocols. The report of the POGM (Pediatric Oncology Group of Madrid)]. AB - OBJECTIVE: The purpose of this study was to reproduce the results obtained by the "BFM Group" in children with NHL and B-ALL treated with BFM 86 and 90 protocols. PATIENTS AND METHODS: From April 1987 until January 1997, we have treated a total of 82 children, 22 with non-B NHL, 49 B-NHL and 11 B-ALL. Forty-four of them were treated according to BFM 86 and 38 according to BFM 90 protocols. RESULTS: Ninety four percent of the patients achieved complete remission (CR) and 15% of these relapsed, 12% of the cases of B NHL/ALL and 23% of the non-B NHL. The 5 year overall survival (Kaplan Meier) was 81% for the B NHL/ALL it was 83% and for non B NHL 77%. The event-free survival was 75% for B-NHL, stages I and II it was 80% and stages II and IV 78%, for B-ALL 72% and for non-B NHL 68%. The median follow up time was 50 months (12-106). CONCLUSIONS: Treatment of NHL and B-ALL with BFM protocols is an effective therapeutic choice, with reproduction of the results of the "BFM group" being feasible. PMID- 9972624 TI - [The response of the hepatitis C and hepatitis G viruses to treatment with recombinant interferon alfa-2b]. AB - OBJECTIVE: The efficacy of recombinant alfa-2b interferon therapy in C-virus (HCV) and G-virus (HGV) in children with chronic hepatitis C was evaluated. PATIENTS AND METHODS: Fifteen patients, between 6 and 16 years of age and positive for HCV of which four were also infected with HGV, were treated with interferon (3 M three times a week for 6 months). The responders were treated for 12 months. HCV RNA, antibodies to HCV, HVC viral genome (expressed as 1000 copy equivalents of HCV genome = 1 keq), HGV RNA (RT/PCR, 5'NCR-NS5), and E2-HGV antibodies were determined before treatment and at 3 and 6 months in all patients and at 12-24 months in the responders. RESULTS: Four HCV patients (27%) with low viral load (mean 36 keg/ml) showed good results after interferon treatment and two of them (13%) with genotypes 1b and 3 according to Simmond's classification showed a maintained response. The four HGV children also showed the same good results and the RNA was negative without sero-conversion to anti-E2 after 12 months of interferon treatment. In the post-interferon treatment period, the HGV RNA appeared again in the serum in 3 of the 4 children. In the child with a maintained response, serum conversion to anti-E2 was not detected. CONCLUSIONS: 1) The current results, with only 13% of the patients reaching a sustained response, question the systematic treatment of all children affected with hepatitis C virus. Since the cost-benefit ratio is not yielding the expected results, such therapy may be reserved for patients with genotype other than 1b and a low level of viral genome. 2) HGV is sensitive to treatment with interferon, although the infection frequently appears again once the treatment is over. PMID- 9972626 TI - [An epidemiological study of the thrombocytopenia with radial aplasia syndrome (TAR) in Spain]. AB - OBJECTIVE: There are numerous published papers on TAR syndrome. Nevertheless, most of them refer to cases or families with several affected members, but we could find no publication epidemiologically analyzing a consecutive series of cases. PATIENTS AND METHODS: We show the characteristics of the six cases with TAR syndrome identified in the consecutive series of 25,967 malformed live born infants detected among 1,431,368 live births surveyed by the ECEMC (Spanish Collaborative Study of Congenital Malformations) since April 1976 until June 1997. RESULTS: The minimal estimated frequency of TAR syndrome in our area is 0.42 per 100,000 live born infants, with a confidence interval of 0.15 to 0.91. There was no known consanguinity among the cases' parents, nor other affected family members. The sex ratio was 1:1. Although it is generally considered that the syndrome is autosomal recessive, genetic heterogeneity cannot be ruled out. CONCLUSIONS: Our cases concur with published data with respect to the low frequency of consanguineous parents. However we did not find a higher proportion of girls affected as has been described previously. PMID- 9972625 TI - [Granulocyte colony-stimulating factor in the newborn neutropenic patient]. AB - OBJECTIVE: To assess the therapeutic effect of G-CSF in newborns with neutropenia. METHODS: Newborn with evidence of both peripheral neutropenia and decreased granulocytic precursors in tibial bone marrow aspirate were included in the study. G-CSF was perfused intravenously over 2 hours at dose of 10 micrograms/kg/day, during 4-8 days. CBC were obtained immediately before each dose of G-CSF. RESULTS: Neutropenia followed neonatal sepsis in four cases and maternal pre-eclampsia in three. Prior to treatment, peripheral blood granulocyte (PMNL) counts ranged from 420 to 1,073/mm3. Once G-CSF infusion was started, counts returned to normal within 24-48 hours. No adverse effects related to G-CSF administration were noticed. CONCLUSIONS: G-CSF induces a significant increase in peripheral PMNL counts in newborn with neutropenia, in the absence of significant toxic effects. Our date suggest a potential role for G-CSF in the prophylaxis and treatment of sepsis in the neutropenic newborn, although widespread recommendation must await further, controlled studies. PMID- 9972627 TI - [A case of a nasal glioma in a newborn infant]. PMID- 9972628 TI - [Nonimmunological fetal hydrops and the oligohydramnios deformation sequence as a manifestation of the twin-twin transfusion syndrome]. PMID- 9972630 TI - [Precocious puberty secondary to tuberculous meningitis]. PMID- 9972629 TI - [The antenatal diagnosis of cystic adenomatoid malformation of the lung. Apropos 2 cases]. PMID- 9972631 TI - [A magnetic resonance (MR) follow-up of central nervous system (CNS) tumors in children: recurrence or radionecrosis?]. PMID- 9972632 TI - [A 2-year-old child with acute respiratory difficulty. Pneumomediastinum and subcutaneous emphysema due to foreign body aspiration]. PMID- 9972633 TI - [Skin burns in 2 premature newborns related to pulse oximetry]. PMID- 9972634 TI - [Ventricular extrasystoles as a form of presentation of neonatal lupus]. PMID- 9972635 TI - [Tramadol via continuous perfusion in the treatment of moderate to severe pain: our experience in 5 cases]. PMID- 9972636 TI - [Idiopathic plantar eccrinitis]. PMID- 9972637 TI - [Pediatric emergencies that turn up at hospital centers]. PMID- 9972638 TI - [Training in pediatric and neonatal cardiopulmonary resuscitation: a task in which we all can and should participate. The Spanish Pediatric and Neonatal Cardiopulmonary Resuscitation Group]. PMID- 9972639 TI - [The risperidone-associated neuroleptic malignant syndrome in a pediatric patient]. PMID- 9972640 TI - [Fecal incontinence caused by a streptococcal perianal disease]. PMID- 9972641 TI - Tongue papillae in goat: a scanning electron-microscopic study. AB - The tongue papillae of 6-9-month-old Jamunapari goats were studied by scanning electron-microscopy. The conical-shaped filiform papillae had 3-6 pointed projections and 6-8 secondary papillae at the free tip and the base of the dorsal surfaced of the tongue, respectively. The convex surfaced fungiform papillae were raised above the lingual mucosa. The vallate papilla was characterized by a papillary groove and an annular pad. The large conical papilla had a round base and a blunt tip without any projection. Two types of lenticular papillae could be distinguished. The irregular surface of all types of papillae revealed microplicae in the form of microridges and micropits. The fungiform papilla was studded with microvilli. The taste pores were oriented on the dorso-lateral surface of the vallate papilla. PMID- 9972643 TI - [Prenatal development of the lamina epithelialis in the phase of vacuolization of villous epithelial cells. Investigations on the intestines of cattle (Bos primigenius taurus L., 1758)]. AB - The development of the bovine small intestine was examined in 39 embryos and fetuses by light microscopic and transmission electron microscopic methods. Special reference was paid to the histogenesis of the ephithelium. In contrast to the duodenum the epithelium of jejunum and ileum undergoes a degeneration by vacuolation of its villous epithelial cells. The demonstration of the acid phosphatase activity of these vacuoles shows their lysosomal character. This degenerative process of the small intestinal epithelium is also known in large intestine where it leads to the destruction of the intestinal villi. Both seem to be part of a 'principle of construction of the intestine of the vertebrates' (Wille, 1984). PMID- 9972642 TI - Morphological and functional aspects of reptilian ultimobranchial gland. AB - The intention of this review is to compare studies on the morphology and histology (light and electron microscopic) of ultimobranchial glands of various groups of reptiles. Moreover, experiments (including our investigations) on suppression or stimulation of the ultimobranchial gland are included. Adult reptiles possess one (on the left side) or two ultimobranchial glands (UBG). The UBG lie just anterior to the heart. Light as well as electron microscopically, the gland has been shown to contain follicles and cell cords (cell aggregates). The follicular epithelium is lined by simple cuboidal or pseudostratified columnar cells. Ciliated and goblet cells may be present in the follicular epithelia in some groups. The lumen may contain a colloid-like substance with desquamated cells or debris. The UBG of reptiles seem to be an active secretory organ with influence on calcium regulation. Other functions of calcitonin have also been suggested in reptiles for example in neurotransmission, in volume regulation, phosphate balance and promotion of bone calcification (at least in juveniles). PMID- 9972644 TI - Investigations on the postnatal development of the macroscopic proportions and the topographic anatomy of the feline spinal cord. AB - The aim of this work was to investigate the postnatal development of the feline spinal cord. Our study showed that the main period of growth leading to the cervical and lumbar enlargements begins after birth and is completed at the age of 5-6 months. Comparing the relationship between the length of the spinal cord and the vertebral column, we found that in contrast to the adult cat, in the newborn cat, length, area and volume of segments show similar values along the spinal cord. This also applied to the length of the vertebrae. Due to a heterogeneous growth, not all segments of the spinal cord end up situated cranial to their corresponding vertebrae. As a consequence, the end of the conus medullaris is still located within the sacral canal in animals older than 2 months. These findings strongly propose that injection into the vertebral canal of the cat have to be performed caudal to the sacral vertebrae. PMID- 9972645 TI - Neuroendocrine cells in the gastrointestinal tract of wild boar. AB - The presence and the distribution of neuroendocrine cells in the gastrointestinal tract of adult wild boar were investigated. The endocrine cells have been identified by means of immunocytochemical techniques using antibodies against serotonin, gastrin, somatostatin, cholecystokinin (CCK), met-enkephalin (MET ENK), gastric-inhibitory peptide (GIP) and glucagon. The number of positive cells for each antiserum in each region was evaluated. Results were compared with data present in the literature and obtained previously by us and other authors in swine and domestic mammals (Ceccarelli et al., 1985, 1987, 1990, 1991, 1995; Capella and Solcia, 1972; Domeneghini and Castaldo, 1981; Peranzi and Lehy, 1984; Krause et al., 1985). PMID- 9972646 TI - A scanning and immunohistochemical study in bovine haemal node. AB - The bovine haemal nodes are lymphatic organs with haemal circulation. The blood circulates inside of them through virtual cavities named sinuses. In these sinuses there is passage of cells and particulate materials from parenchyma to sinuses and vice versa. For this passage temporal overtures exist in the sinus walls. The sinus wall is composed of endothelial cells, basal membrane and reticular cells. Our results have demonstrated that type IV collagen was one of the basal membrane constituents in bovine haemal nodes and by this constitution a dynamic equilibrium of the sinus walls was permitted. PMID- 9972647 TI - 3-D confocal laser scanning microscopy used in morphometric analysis of rat Purkinje cell dendritic spines after chronic ethanol consumption. AB - A confocal laser scanning microscope (with a 543 nm laser) was used for imaging rat Purkinje cell dendritic spines at high 3-D resolution. In a nutritionally controlled study of the rat, 5 months of ethanol consumption was demonstrated to alter the spines of Purkinje cell dendrites in rat cerebellum. Intact spines showed significant elongation after ethanol exposure, whereas this neuromorphological alteration could not be detected in controls. Spine elongation could be regarded as compensative growth of spines in search of new synaptic contacts due to alcohol induced cell loss. PMID- 9972648 TI - Characterization of lateral musculature in the striped weakfish (Cynoscion striatus Cuvier). AB - Histochemical and ultrastructural studies were performed on lateral musculature from individual female weakfish (Cynoscion striatus Cuvier). Based upon SDH, PhR, Sudan and myosin-ATPase determinations, different kinds of red, pink and white fibres were discerned at the anterior, medium and posterior regions. Levels of glycolytic activity increased from red to white fibres, being intermediate in the pink ones. Contrarily, oxidative activity decreased from red to pink and white fibres. Histochemical stain showed a complex distribution of fibre types in each layer. A considerable variation in size and distribution was also found among fibres. PMID- 9972649 TI - Immunohistochemical study of endocrine cells in the gastrointestinal tract of the Philippine carabao (Bubalus bubalis). AB - The distribution and frequency of occurrence of endocrine cells in the gastrointestinal tract of the Philippine carabao (Bubalus bubalis) were studied by immunohistochemistry. Fourteen types of immunoreactive (IR) endocrine cells were revealed. Among the cell types, only chromogranin, serotonin, and bovine pancreatic polypeptide (BPP) were present in the entire gut, while the others showed restricted distribution: somatostatin, gastrin, and cholecystokinin in the abomasum and small intestine; methionine-enkephalin-Arg6-Gly7-Leu8, motilin, neurotensin, secretin, gastric inhibitory peptide, and substance P in the small intestine; peptide tyrosine tyrosine (PYY) in the large intestine; and glucagon in the whole intestinal tract. Most of the cell types showed peak density in the pyloric, duodenal, or rectal region. The highest cell type heterogeneity was observed in the duodenum. The distribution profile of the gut endocrine cells in the carabao is closely related to that in the Holstein cattle. Important findings include the occurrence of BPP-IR cells in the entire gut and the high frequency of PYY-IR cells in the large intestine. PMID- 9972651 TI - [What's new in the treatment of Dupuytren's disease?]. AB - Among the recent advances in the field of Dupuytren's contracture, the authors reviewed a series of 171 patients treated by percutaneous needle fasciotomy. Among the 198 hands (241 fingers), 65 were reviewed with a mean follow-up of 2.5 years. Mean age was 62 years and delay between onset and treatment 6.8 years. Rupture of the cords was performed only in the palm in 154 cases, palmo-digital in 82 and purely digital in 5 cases. Complications were rare and benign without tendon or vascular bundle injury. Postoperative gain was essentially observed on the metacarpo-phalangeal joint and recurrence rate was high despite the short follow-up (progression of the disease 54% of cases). The ideal indication for this simple and reliable technique is an elderly patient with a prominent cord and predominant lack of metacarpophalangeal extension. PMID- 9972650 TI - Gross anatomy of the pancreatic lobes and ducts in six breeds of domestic ducks and six species of wild ducks in China. AB - A previously unreported pancreatic duct was found by Liu (1989) in Pekin ducks. This duct has now been consistently found in six breeds of domestic ducks and six species of wild ducks in China. For purposes of Nomina Anatomica Avium it is hereby called the 'first pancreatic duct' (Ductus pancreaticus primus) since it enters the duodenum at or near the flexure where the descending duodenum becomes the ascending duodenum. All other pancreatic ducts enter the duodenum later, closer to where it joins the jejunum. This first pancreatic duct drains the caudal extremity of the dorsal lobe of the pancreas and can be easily exteriorized for experimental purposes. Within the parenchyma of the dorsal lobe of the pancreas this duct communicates with the dorsal pancreatic duct. In the present study of the gross anatomy of the pancreatic lobes of domestic and wild Chinese ducks we describe and illustrate variations in position and number of all biliary and pancreatic ducts. PMID- 9972652 TI - [What's new concerning carpal tunnel syndrome?]. AB - Despite its frequency, carpal tunnel syndrome is still a subject of debate in the literature. Is a clinical diagnosis sufficient to justify the indication for surgery? Electromyography appears to play a very important role and, apart from its diagnostic and medicolegal value, may reveal associated lesions able to account for persistence of certain symptoms in the medium- or long-term; about which the patients must be informed. More general social questions are raised by the recognition of occupational carpal tunnel syndrome and its economic implications. Medical treatment by nocturnal resting splint still has a real place and endoscopy constitutes an alternative to classical open surgery. Surgical techniques must comply with rigorous rules, the only way of ensuring security and prevention of recurrences, which are difficult to treat. PMID- 9972653 TI - [What's new in surgery of flexor tendons?]. AB - After revealing tendon healing and the international classification adopted in 1980 for flexor tendon lesions, the author reviews the primary tendon repair procedures and the various postoperative mobilization protocols. The current tendency is towards early active mobilization with a protection orthosis. The various secondary surgical procedures are then critically discussed: secondary suture, tendon release, one-stage or two-stage tendon graft, total anterior tenoarthrolysis, tendon transfer, vascularized tendon graft, active tendon implants. PMID- 9972655 TI - [What's new in upper limb skin expansion?]. AB - The indications for skin expansion of the upper limb are now well defined. Based on a series of 56 cases, the authors confirm that a rigorous technique and good management of complications can minimize failures of the method. Technical progress and new biomaterials certainly allow further reduction of these complications and possibly the development of new indications. PMID- 9972654 TI - [What's new in syndactyly?]. AB - In the light of the international literature over the last ten years, the author reviews the surgical treatment of syndactyly, including the optimal age of operation, surgical treatment without grafts, treatment of digital extremities, prevention of commissural retraction, and long-term results. PMID- 9972656 TI - [What's new in nail surgery?]. AB - The author review the literature concerning progress in nail surgery. He presents several basic research studies on the blood supply of the ungual apparatus, very rare studies on pathophysiology and the contribution of magnetic resonance imaging. In practice, progress or new techniques in traumatology (haematomas, wounds of the nail bed and matrix, defects, distal amputations through the nail) and in the context secondary dystrophic lesions are considered. In particular, the indications for emergency and secondary microsurgery are defined. The only novelty in neoplastic disease concerns the discovery of a new tumour: onychomatricoma. PMID- 9972657 TI - [What's new in cosmetic surgery of the hand? Technical notes]. AB - The author analyses the aesthetic aspects of the hand in three circumstances: trauma, rheumatism, and ageing. He describes the unsightly appearance of certain grafts and flaps and certain amputation stumps and malunions following trauma and emphasizes the cosmetic indication for finger transfer to an adjacent finger in four-finger hands. The main indications for rheumatic digital deformities concern distal deformities: DIP arthrodesis or arthroplasty depending on the finger. In the context of ageing of the hand, related to excess skin and prominent veins, the author proposes a one-stage operation via a palmar incision. PMID- 9972658 TI - [External rhinoplasty: a useful approach for a young plastic surgeon]. AB - Among the frequently performed plastic surgery operations, rhinoplasty is the most difficult to obtain consistently good results. It is very challenging for young plastic surgeons to modify the external appearance of the nose and restore or maintain a good airway. The external approach has alleviated some of the problems due to understanding and learning of the rhinoplasty operation. Actually, open rhinoplasty allows better visualization of anatomical deformities and better manipulation of tissues allowing better integration of nasal anatomy and physiology. This paper reviews a personal series of 82 patients operated via an open approach between October 94 and October 97. During the same period, 24 patients were operated via an endonasal or percutaneous approach (osteotomies). Indications, advantages and disadvantages of the open approach are discussed. The various techniques used in this series are described and then critically analyzed. In open rhinoplasty, our present revision rate is 8.5%. In conclusion, the open approach seems to be useful for young rhinoplastic surgeons. PMID- 9972659 TI - [Role of surgery in the treatment of hemangiomas. A retrospective study apropos of 29 surgically treated children]. AB - Conservative management is usually proposed for common childhood hemangiomas because most lesions resolve spontaneously. The authors report 29 cases of children with hemangiomas treated surgically. Surgical indications were defined at various stages. The study concerned 29 children operated in our pediatric surgery and plastic surgery departments between 1989 and 1995. The average postoperative follow-up was 3 years and 8 months. The average age of the patients was 5 years; two-thirds of children were girls. The hemangioma was a very large lesion, subcutaneous and cutaneous (mixed) in 23 cases, only subcutaneous in 2 cases, only cutaneous in 4 cases, and was located on the face in 19 cases. Six complications (5 ulcerations, 1 Kassabach-Merritt syndrome) were observed. PMID- 9972660 TI - [CO2 laser skin resurfacing. Critical analysis of recent literature]. AB - Over recent years, there appears to have been an explosion of public interest in facial rejuvenation. With the recent development of short-pulsed high-peak power and rapidly scanned carbon dioxide (CO2) lasers, it is now possible to remove photo-damaged skin precisely and reproducibly, while leaving behind a narrow zone of thermal damage. This development has generated tremendous interest in laser skin resurfacing as a technique to reverse photoaging. However, the overall review of the existing literature, except for very few publications, reveals several major methodological problems. The use of CO2 laser for cosmetic purposes is very recent and therefore requires further justification, standardization and regulation based on well designed studies. Most of the recent published data correspond to case reports, rather than well-designed scientific studies. For these reasons, this field needs more clinical trials and epidemiological investigations such as prospective cohorts or case-control studies, to provide new knowledge in this field. PMID- 9972661 TI - [A new method of covering skin loss of the internal canthus: paralateronasal flap]. AB - The author describes a new procedure of coverage of the medial canthus: paralateronasal flap. It is a cutaneous rotation-advancement flap with random vascularisation ensured by the dermal vascular plexus. It is vertical and S shaped. Its first curve is concave laterally and ascends widely to the lateronasal area, and its second lower curve is concave medially, following the nasolabial fold. This flap has been used 14 times, mostly to repair defects caused by excision of skin cancers of the medial canthus. Mean follow-up is 18 months. The aesthetic results obtained are very satisfactory. The author compares the advantages of the paralateronasal flap with present techniques and thinks that this new flap should find its place in the therapeutic arsenal for repair of the medial canthus. PMID- 9972662 TI - [Physicians' duty to inform in the jurisprudence of the Appeals Court]. PMID- 9972663 TI - Hemorheological alterations and hypercoagulable state in deep vein thrombosis. AB - Deep vein thrombosis (DVT) seems to be related to a hypercoagulation and definite hemorheological alterations, but the importance of these alterations in the development of thrombotic events in the deep vein system has not been established. The present study examines both aspects in a group of 55 patients with DVT; the presence of a hypercoagulable state was assessed by quantifying the prothrombin fragment 1+2 (F1+2) and the thrombin-antithrombin III complex (T-AT), and the main hemorheological parameters were evaluated in the acute state and 6 and 12 months later. The results show marked hemorheological, F1+2, and TAT alterations in the acute phase. After 12 months the pattern shows a modest improvement, but erythrocyte aggregation, fibrinogen, F1+2 and T-AT remain increased with respect to the control group (8.51 +/- 1.43; 331 +/- 81 mg/dl; 1.33 +/- 0.60 nmol/l; 3.54 +/- 1.71 ng/ml vs. 8.10 +/- 1.40; 230 +/- 38; 0.94 +/- 0.40; 1.56 +/- 0.59, respectively). These data suggest that the thrombotic event could be influenced by the previous rheological situation and hypercoagulable state. PMID- 9972664 TI - Methods for studying leukocyte filterability in undiluted blood from intermittent claudicants. AB - Leukocytes are characterised from their influence on the filterability of undiluted blood from patients with PAOD (intermittent claudicants - Fontaine Stage II) and a group of sex and age-matched controls. Undiluted blood was filtered through 5 microm Nuclepore (Hemafil) filters for 300 s, at 711 Pa and room temperature, using a custom-made constant pressure filtrometer. Four populations of leukocytes are identified in both groups. In the control group, 94.4% of the leukocytes are identified as fast leukocytes with a transit time of 1.8 s. The remaining white cells are recognised as slow flowing leukocytes and subdivided into three further sub-populations. The first of these (SL1; 2.8% of total leukocyte count) is characterised by a transit time of 31.7 s, a second population (SL2; 1.5% of total leukocyte count) by a transit time of 145.8 s while the remaining cells are identified as pore blockers (PB) under these conditions. A similar rheological classification is valid in the patients but the sum of the three minor populations is elevated compared to controls (p = 0.001) although there is no overall leukocytosis. The only significant difference in flow properties of any blood cells, between the two groups of volunteers, is seen in the major population of leukocytes with an elevated transit time of 2.4 s. Stepwise regression analysis identifies the concentration of fast leukocytes, SL2 and PB as the major variables affecting blood flow through the filter. It is argued that the higher concentration of SL2 and PB probably reflect the increased sensitivity of neutrophils to physical stimuli. PMID- 9972665 TI - Essential hypertension: leukocyte rheology and polymorphonuclear cytosolic Ca2+ content at baseline and after activation. AB - In 24 hypertensives we evaluated, at baseline, the leukocyte filtration parameters (using the St. George's Filtrometer), polymorphonuclear (PMN) membrane fluidity (with the fluorescent probe 1-[4-(trimethylamino)phenyl]-6-phenyl-1,3,5 hexatriene [TMA-DPH]) and PMN cytosolic Ca2+ content (with the fluorescent probe Fura 2-AM). In a subgroup of hypertensives (n = 17) the PMN filtration parameters, PMN membrane fluidity and cytosolic Ca2+ content were evaluated after in vitro chemotactic activation (prolonged for 5 and 15 min) with two stimulating agents (4-phorbol 12-myristate 13-acetate [PMA] and N-formyl-methionyl-leucyl phenylalanine [fMLP]). It was evident, from the baseline data, that there was a significant difference in the mononuclear (MN) initial relative flow rate (IRFR), clogging rate (CR) and clogging particles (CP), and in PMN cytosolic Ca2+ content. There were, however, no differences in the filtration parameters of unfractionated leukocytes and PMNs or in PMN membrane fluidity. After activation, in normals and in hypertensives, a significant variation in PMN filtration parameters was evident. In normals no variation was present in PMN membrane fluidity or cytosolic Ca2+ content after activation. In hypertensives, however, we found an increase solely in PMN cytosolic Ca2+ content after fMLP activation. After PMN activation (at 15 min) one parameter (IRFR) of PMN filtration distinguished normal subjects from hypertensives. No difference between the two groups was found in PMN membrane fluidity or PMN cytosolic Ca2+ content after PMN activation. PMID- 9972666 TI - Linear and nonlinear elastic modelling of the deformation of vasa vasorum. AB - The authors present analytical and numerical approaches of the deformation of venous and arterial vessels vasa vasorum. An elastic behaviour of the vessel wall is supposed. It is shown that a normal range of intraluminar pressure induces a small deformation in the vasa vasorum in arteries. According to the nonlinear elastic behaviour, a larger deformation is induced in venous vasa vasorum is rapidly obtained. Increased pressure has serious consequences, especially on the flow in vasa vasorum and induces decrease of oxygen transport. This phenomenon could be one of the generating factors of atherogenesis and ischemia. PMID- 9972667 TI - An animal model to study erythrocyte senescence with a narrow time window of erythrocyte production: alterations in osmotic fragility and deformability of erythrocytes during their life span. AB - Using the model in which the entire RBC population was nearly synchronously produced following the induction of spherocytic anemia in the rabbit with antibody serum, we determined the changes of RBC osmotic fragility and deformability with aging. The results showed that the osmotic fragility increased with the RBC aging process in a nonlinear manner, being much more profound in the later part of the RBC life span. The RBC deformation index (DI) was measured by an ektacytometry. It is found that the DI decreased with RBC aging in a nonlinear fashion, with increasingly greater changes in the later part of the RBC life span. The alterations of RBC mechanical properties with aging may be attributable to a number of factors, including changes of RBC size and shape, and the viscoelasticity of the cytoplasm and membrane. PMID- 9972668 TI - Measurement of red blood cell aggregation in a "plate-plate" shearing system by analysis of light transmission. AB - The analysis of light reflection from or transmission through a blood sample under defined shearing conditions is widely used to assess red blood cell (RBC) aggregation. Different shearing geometries have been used to generate a constant shear rate within the blood sample, including "cone on plate" and Couette systems. In this study, a rotating glass plate, together with a parallel stationary plate, was used to generate a given shear rate at the point of light transmission measurement. The system gave reproducible results and proved to be sensitive to alterations in RBC aggregation. A comparison between different RBC aggregation parameters that can be calculated using the same light transmission curves (syllectograms) was also made. The index calculated by integrating the area under the syllectogram (M index) was found to be the most appropriate aggregation parameter to be used for comparisons between two groups of blood samples with different aggregation characteristics. PMID- 9972669 TI - Disturbed blood flow structuring as critical factor of hemorheological disorders in microcirculation. AB - Blood flow structuring is a phenomenon of co-ordinated self-organization of RBCs in the normal flow in microvessels which actually defines the blood rheological properties in their lumina. Under conditions of undisturbed macrocirculation and normal conductance of microvessels the blood flow structuring is a determining factor of the fluidity of the driven blood. The dynamic structuring of blood flow prevails in advancing of the driven RBCs with plasma in the shear field induced in microvessels. Term "blood flow structuring" was introduced to describe the self-organised behavior of the RBCs and plasma advancing in the arterio-venular direction in the rapidly perfused microvessels. It implies primarily the availability of parietal plasma layer and of RBCs driven in the axial core, the tank treading, deformation and orientation of the red cells, i.e., of their self optimizing adaptive behavior which minimizes energy dissipation. Many local hemorheological disturbances in the microvessels are related to intensified RBC aggregation and to the subsequent local accumulation in the microvascular lumina, thus entailing disorders of the blood flow structuring. This, in turn, results in the decrease of flow velocity, to full blood stasis, despite a preserved local arterio-venous driving pressure gradient. Elevated blood plasma viscosity and considerably curtailed RBC deformability might also entail retardation and even stoppage of the RBC flow in microvessels. The transition of blood flow to blood stasis and again to blood flow represents a synergetic process in the critically underperfused microvascular networks. As to the WBCs and thrombocytes, they are not involved in the normal blood flow structuring in microvessels, but they can largely affect both the blood flow normal structuring and the flow velocity under various pathological conditions. The presented theoretical concept accounts for a wide variety of transition patterns from the normal to the pathological hemorheological phenomena in the microcirculation. PMID- 9972670 TI - Role of colestipol in the treatment of hyperthyroidism. AB - The enterohepatic circulation of thyroxine (T4) and triiodothyronine (T3) is higher in thyrotoxicosis. Bile-salt sequestrants bind iodothyronines and thereby increase their fecal excretion. We, therefore, evaluated the effect of colestipol hydrochloride administration on clinical and biochemical indices of patients with hyperthyroidism. In a prospective, controlled trial, ninety-two adult volunteers with Graves' disease, toxic autonomous nodule or toxic multinodular goiter were randomly assigned into the following treatment protocols: Group 1, 30 mg of methimazole (MMI) and 20 g of colestipol-hydrochloride (COL) daily; Group 2, 30 mg of MMI daily; and Group 3, 15 mg of MMI 20 g of COL daily. The patients were further classified into Group A, severe hyperthyroidism (baseline levels of total T3 (TT3) > or =5 nmol/l) and Group B, mild to moderate thyrotoxicosis (baseline levels of TT-3<5 nmol/l). Crook's clinical index, serum free T4 (FT4), TT3 and thyroid stimulating hormone (TSH) levels were determined before (WO), following one week (W1) and two weeks (W2) of treatment. Serum TT3 level decreased (mean+/ SE) at W1 by 40.8+/-2.6% of WO in Group1 and by 29.2+/-2.4% in Group 2 (p<0.001), and down further to 47.8+/-3.0% at W2 in Group 1, and 40.6+/-2.8% in Group 2 (p=0.01). Serum FT4 level decreased (mean+/-SE) from WO to W1 by 31.7+/-2.7% in Group 1 and by 16.2+/-3.1% in Group 2 (p=0.005), and down to 49.1+/-2.8% of WO at W2 in Group 1 and to 38.7+/-3.5% in Group 2 (p=0.07). In sub groups B COL was not effective in reducing thyroid hormone levels nor in ameliorating the clinical status of the patients. However, in Group A3 COL lowered FT4 (p=0.001) and TT3 (p=0.05) levels as compared to group A2. At W2 the clinical hyperthyroidism score improved faster in Group A1 (p<0.001) and Group A3 (p=0.012) as compared to the control Group A2. In conclusion, COL is an effective and well tolerated adjunctive agent in the treatment of hyperthyroidism. Its main effect is in severe cases of thyrotoxicosis, and in the first phase of treatment. As adjunctive COL treatment in hyperthyroidism allows reducing MMI dosage it may decrease the rate of dose dependent MMI side effects. PMID- 9972671 TI - Hormonal replacement therapy in menopausal women with a history of hyperprolactinemia. AB - Hyperprolactinemia is involved in almost 30% of infertility problems. At the onset of menopause, prolactin levels often decrease; however, no data are available regarding the course of hyperprolactinemia after menopause with hormonal replacement therapy (HRT). A retrospective study was undertaken in our department to evaluate the potential role of estrogens in women with a history of hyperprolactinemia. Twenty-two patients, with hyperprolactinemia before menopause, were followed-up. Group I included 11 patients who withdrew bromocriptine treatment when menopause was confirmed. These patients were placed on HRT with no other medication administered. HRT was a combination of percutaneous estradiol gel and an oral progestin. Group II included 7 women treated by bromocriptine before menopause and after menopause concomitantly with HRT. Group III included 4 patients who did not receive HRT or other treatments once menopause was diagnosed. The mean serum prolactin level was unchanged in Group I (22.8+/-21.7 before and 22.8+/-16.1 ng/ml after HRT) while it increased but not significantly from 8.1+/-5.2 to 16.0+/-11.7 ng/ml in Group II. The mean duration of HRT was 42.8+/-23.8 (7-81) and 37.3+/-31.0 (6-99) months in Group I and II respectively. In Group III patients, PRL levels decreased spontaneously from 61.2+/-39.8 to 33.0+/-34.7 ng/ml. In conclusion, in this population of menopausal patients with a history of moderate hyperprolactinemia, HRT did not seem to affect plasma prolactin levels. PMID- 9972672 TI - Gender-dependent characteristics of the hypothalamo-corticotrope axis function in glucocorticoid-replete and glucocorticoid-depleted rats. AB - The aim of the present study was to determine the role of the endogenous sex steroid environment in the hypothalamo-corticotrope (HC) function in both sham operated (SHAM) and bilaterally adrenalectomized (ADX) rats. For this purpose adult rats of both sexes were used 3 and 6 weeks after either SHAM or ADX. The results indicate that: a) in SHAM animals, basal plasma ACTH levels were significantly higher in females than in males, and this sexual dimorphism was overridden by ADX, regardless of the time post-surgery; b) although basal anterior pituitary (AP) ACTH content was similar in SHAM animals of both sexes, 3 and 6-week ADX induced higher AP ACTH in males than in females; c) at 3- and 6 weeks, ADX rats of hoth sexes had an AVP:CRH ratio (r), in the median eminence (ME) and medial basal hypothalamus (MBH), increased several fold over the respective SHAM-value and, although no sexual dimorphism was found at week 3 post ADX, by 6-weeks post ADX, these ratios were significantly higher in both brain tissues of females than in those of males; and d) the in vitro ME CRH and AVP output in response to high potassium concentrations (hK+; 28 and 56 mmol/I), was concentration-related, regardless of sex and surgery, and was characterized by enhanced secretion of neuropeptides by MEs from ADX in comparison to SHAM rats of both sexes, and a sexual dimorphism was found in this parameter, consisting in general, in greater neuropeptide output from tissues of female than of male animals. Our results indicate that: 1) there is a gender-dependent characteristic of the HC axis function in glucocorticoid-replete rats and 2) the absence of the glucocorticoid negative feedback mechanism is responsible for either the expression or for the override of the sexual dimorphism in different parameters, a phenomenon which dependent on the time elapsed after ADX. PMID- 9972673 TI - Efficacy of combined treatments in NIDDM patients with secondary failure to sulphonylureas. Is it predictable? AB - The treatment of NIDDM patients with secondary failure to sulphonylurea is a common problem. We performed a crossover study in 50 NIDDM patients with secondary failure to glibenclamide by comparing the addition to sulphonylurea of either a low-dose bedtime NPH insulin or a t.i.d. oral metformin and by analyzing treatment efficacy in relation to patient and disease characteristics. Both combined therapies clearly improved glycaemic control. HbA1 c were similarly reduced by the addition of either bedtime NPH insulin (7.6+/-0.34 vs 8.7+/-0.35, p<0.01) or metformin (7.6+/-0.22 vs 8.6+/-0.31, p<0.01). Also fasting plasma glucose (FPG) and post-prandial plasma glucose (PPPG) significantly decreased (p<0.01) with both treatments. Bed-time NPH insulin was more effective on FPG reduction than metformin (-36+/-2% vs -25+/-2%, p<0.01); in contrast, metformin addition was more effective on PPPG reduction than bedtime NPH insulin addition ( 30+/-2% vs 20+/-3%, p<0.01). Serum cholesterol was marginally but significantly decreased after metformin (5.49+/-0.19 vs 5.91 +/-0.18 mM, p<0.05) but not after NPH insulin. Body weight increase was significantly greater after insulin addition than after metformin (1.47+/-0.25 Kg vs 0.64+/-0.17 p=0.02). All patients preferred the addition of metformin rather than NPH insulin. None of the measured clinical and metabolic variables (before treatment FPG and PPPG, HbA1 c, post-glucagon C-peptide levels, insulin sensitivity, patient age, BMI and diabetes duration) significantly correlated to the efficacy of the two combined treatments studied. In conclusion, in NIDDM patients with secondary failure to sulphonylureas the addition of either low-dose bedtime NPH insulin or t.i.d. metformin is similarly effective in improving glycaemic control. Metformin is better accepted by patients and provides a modest advantage in terms of body weight and cholesterol levels. The most common clinical and metabolic variables are not useful for predicting the efficacy of these two combined treatments. PMID- 9972674 TI - Occurrence of thyroid autoimmunity and dysfunction throughout a nine-month follow up in patients undergoing interferon-beta therapy for multiple sclerosis. AB - Thyroid autoimmunity and dysfunction are a well known side effect of IFN alpha therapy for viral hepatitis and tumors, while the IFN beta effects on the thyroid gland in neurological patients have not been studied. The aim of this longitudinal study was to look for the appearance of thyroid autoimmunity as well as for the occurrence of overt thyroid disease in the patients affected by multiple sclerosis (MS) treated with IFN beta 1b. Eight patients (4 males, 4 females) undergoing r-IFN beta 1b treatment (8 M.U. every other day for 9 months) for relapsing remitting multiple sclerosis entered the study. We have analyzed thyroid function parameters and auto antibody levels before and after 1, 2, 3, 6 and 9 months of therapy. None of them referred to familiar thyroid pathology or presented clinically overt thyroid disease except for one patient (case 4) who showed TPO-Ab pretreatment positivity and another (case 8) who was in therapy with Levothyroxine 100 microg/die for multinodular goiter. The number of patients with appearance of thyroid antibodies has slowly increased, until the third month of therapy with 3 patients out of 7 positive for TPO-Ab. The only case of overt thyroid dysfunction reported by us appeared after nine months of therapy and consisted of a hypothyroidism. Our data suggest that short-term interferon beta treatment is able to induce thyroid autoimmunity (42.8%) and dysfunction (12.5%). PMID- 9972675 TI - p53 protein and its messenger ribonucleic acid in human adrenal tumors. AB - The role of p53 tumor suppressor gene in the pathomechanism of adrenal tumors was investigated by measuring p53 protein and its messenger ribonucleic acid (mRNA) in 12 normal human adrenals as well as in 56 adrenal tumors (7 aldosterone producing adenomas, 5 adrenocortical adenomas causing Cushing's syndrome, 19 non hyperfunctioning adrenocortical adenomas, 5 adrenocortical carcinomas, 12 pheochromocytomas, 3 myelolipomas, 4 ganglioneuromas and 1 hemangioma). The p53 protein concentration was significantly increased in aldosterone-producing adenomas (394+/-36 pg/mg cytosolic protein, mean+/-SE, vs 266+/-18 in normal human adrenals), whereas the concentration of this protein in Cushing's adenomas, non-hyperfunctioning adrenocortical adenomas, pheochromocytomas, and in all but one adrenocortical carcinomas was similar to that measured in normal human adrenal tissues. One adrenocortical carcinoma tissue showed very high p53 protein content (3000 pg/mg cytosolic protein). By contrast, myelolipomas (23+/-20) ganglioneuromas (43+/-15) and a hemangioma (11 pg/mg cytosolic protein) had very low p53 protein content. Northern blot analysis revealed the presence of p53 mRNA in each adrenal tissue examined with highest levels in aldosterone-producing and Cushing's adenomas. It is possible that the differences in p53 protein and/or mRNA contents reflect corresponding differences in the pathogenetic importance of p53 alterations in these types of adrenal tumors. PMID- 9972676 TI - Chronic recurrent stress due to panic disorder does not precipitate Graves' disease. AB - A role of psychic stress in precipitating hyperthyroid Graves' disease has been suggested, but the evidence in support of this pathogenetic mechanism is conflicting. In this study we investigated the possible occurrence of Graves' disease in patients with panic disorder, a psychiatric condition characterized by recurrent endogenous stress. The study group included 87 consecutive patients suffering from panic disorder since 1 to 30 years: 17 males (mean age 31.3, range 26-43 years) and 70 females (mean age 37.6, range 15-73 years). Two hundred and sixty-two normal subjects with no present or past history of psychiatric disorder served as controls. Patients were submitted to a full evaluation of the thyroid that included physical examination, assays for free thyroid hormones, TSH, thyroglobulin (TgAb), thyroperoxidase (TPOAb) and TSH receptor (TRAb) antibodies, and thyroid echography. The prevalence of circulating TgAb and/or TPOAb in patients with panic disorder did not differ from that in the control group. Twelve patients with panic disorder (13.7%) had circulating TgAb and/or TPOAb, but none had TRAb. Three out of 12 patients with thyroid antibodies, indicating a genetic susceptibility to autoimmune thyroid disease, had a family history of clinical thyroid autoimmunity, and 4 of them had a hypoechogenic pattern of the thyroid at ultrasound suggesting autoimmune thyroiditis. None of the patients with panic disorder had a previous history of hyperthyroidism. On examination, clinical hyperthyroidism or endocrine ophthalmopathy were not found in any of them. A small goiter was appreciated by palpation in 16 patients (18.3%). Free thyroid hormones and TSH were within the normal range in all patients but one: a 55-year old lady with normal serum free thyroid hormones and undetectable TSH. During an 18-month follow-up she did not develop hyperthyroidism and her TSH spontaneously returned in the normal range. Considering the individual duration of panic disorder, evidence for previous or present Graves' hyperthyroidism was not found for a total of 478 patient-years of exposure to recurrent endogenous stress in the whole study group, and for a total of 39 patient-years in patients with a genetic susceptibility to autoimmune thyroid disease. In conclusion, we found that recurrent endogenous stress did not precipitate Graves' hyperthyroidism in a series of 87 patients with panic disorder, encompassing a total of 478 patient-years of exposure to stress. Failure to activate the hypothalamic-pituitary-adrenal axis by endogenous stress due to panic disorder as opposed to exogenous stress due to life-events might explain why panic disorder does not precipitate Graves' hyperthyroidism. PMID- 9972677 TI - Evaluation of growth hormone bioactivity using the Nb2 cell bioassay in children with growth disorders. AB - The Nb2 cell bioassay could be a useful tool for evaluating human growth hormone (hGH) bioactivity, but is not specific for hGH since it relies on the ability of the hormone to produce effects by cross-reacting with the lactogenic receptor on Nb2 cells. We studied the biological activity of both endogenous and exogenous hGH in short patients using the Nb2 bioassay after inhibiting the mitogenic effect of the other lactogenic hormone, that is human prolactin (hPRL), by adding a specific antibody against hPRL to each assay. The in vitro study showed a significant (p<0.0001) increase in Nb2 cell proliferation when increasing concentrations of highly purified hGH were added to the cell culture. A complete inhibition of Nb2 cell replication was observed after adding a specific antibody against hGH. The in vivo study showed a significantly (p<0.0001) lower hGH bioactivity (4.90+/-0.28 ng/ml) evaluated during stimulation tests in 9 children with total idiopathic GH deficiency, mean age 9.25+/-1.99 years, in comparison with that found in 11 short children with normal growth velocity, mean age 8.22+/ 1.41 years (12.25+/-1.19 ng/ml). Likewise, serum GH levels measured by immunofluorometric assay IFMA in the same serum samples were significantly (p<0.001) lower in the 9 GH-deficient (1.97+/-0.37 ng/ml) than in the 11 short children (21.85+/-2.71 ng/ml). Moreover, we evaluated GH concentrations using both IFMA and the Nb2 cell bioassay in serum samples collected from another 11 idiopathic GH-deficient children, mean age 10.71+/-1.18 years, before and then, 6 and 24 hours following the 1 st injection of r-hGH (0.1 IU/kg sc). Serum GH values measured by both IFMA and Nb2 bioassay significantly (p<0.0001) increased 6 hours after r-hGH administration and decreased to reach basal levels after 24 hours. In conclusion, the Nb2 cell bioassay with minor modifications seems to provide a specific and sensitive assessment of hGH bioactivity. PMID- 9972678 TI - Thyrotropin receptor antibodies in black South African patients with Graves' disease and their response to medical therapy. AB - Graves' disease is increasing in incidence amongst urban black South Africans. The pathogenic role of thyrotropin receptor antibodies (TRAb), crucial in other populations, has not been formally evaluated in African communities. We therefore prospectively investigated the prevalence of TRAb in 30 consecutive urban black South African patients with classical Graves' disease at the onset of their illness. This was compared with the frequency of thyroid microsomal and thyroglobulin antibodies in the same patients. Ten patients with euthyroid goitres unrelated to Graves' disease and 10 healthy controls were also studied. Twenty of the hyperthyroid patients were retested 4-6 months after starting carbimazole therapy and ten of them again after 1 year. Initially 83% of patients were positive for TRAb as against 54% for thyroid microsomal and 1 7% for thyroglobulin antibodies. After 4-6 months of treatment, 65% of patients still had elevated (>15% inhibition of binding) TRAb titres, while at 1 year this had dropped to 40% (4 out of 10 patients). All positive patients had relapsed biochemically, while TRAb negative patients were all in remission. We conclude that TRAb are a sensitive and specific marker of Graves' disease in black South Africans and closely parallels the response to medical therapy at 1 year. However, their predictive value for delayed relapse requires the study of a larger cohort of patients over a longer time-frame. PMID- 9972679 TI - Long-term preoperative management of thyrotropin-secreting pituitary adenoma with octreotide. AB - Thyrotropin (TSH)-secreting pituitary adenomas are the less frequent form of presentation of pituitary tumors. Selective transsphenoidal surgical resection of the tumor is the treatment of choice. Given that native somatostatin inhibits TSH secretion, treatment with somatostatin analogues has been recently employed in patients with unresectable tumors or after surgery. We report on the case of a 58 year-old man with a TSH-secreting pituitary adenoma who was treated with octreotide for long-term before neurosurgery. The patient was referred to us because of a pituitary mass on CT scanning. Hormonal evaluation resulted in hyperthyroidism with high serum TSH concentrations. Serum alpha subunit concentration was elevated and TSH response to exogenous TRH stimulation was absent. Magnetic resonance imaging of the hypothalamic-pituitary area confirmed the presence of a pituitary mass (2.0 by 1.8 by 1.7 cm). Acutely administered subcutaneous octreotide (100 microg) was followed by a reduction of the serum TSH concentrations. Therefore, the patient received octreotide, 100 microg three times daily for 12 months. At first month after beginning therapy serum TSH, free thyroxine, total triiodothyronine, and alpha subunit concentrations were normalized and persisted into the normal range for the next 11 months. On the other hand, a shrinkage of the tumor mass (1.6 by 1.7 by 1.4 cm) was noted after 6 months of octreotide therapy, however, its volume did not modify in the following next months. Then, the tumor was removed by transsphenoidal surgery and the diagnosis was confirmed by immunohistochemical staining. This case demonstrates that long-term treatment with octreotide gave rise to a normalization of the thyroid function and a reduction of the tumor volume before surgery. This clinical observation suggests that octreotide therapy might be useful in preparation for pituitary surgery in patients with TSH-secreting pituitary adenomas. PMID- 9972680 TI - False-positive diagnosis of adrenal pheochromocytoma on iodine-123-MIBG scan. AB - 1-123 metaiodobenzylguanidine (1-123 MIBG) scintigraphy is known for its high specificity in detecting pheochromocytoma and other tumors of neural crest origin. In this rare case report, we describe a definite adrenocortical adenoma that demonstrated false-positive uptake at I-123 MIBG scintigraphy and a remarkable accumulation of 75-SE-6-beta-selenomethyl-norcholesterol. PMID- 9972681 TI - Is thyroxine during lithium therapy necessary? PMID- 9972682 TI - Synthetic peptides and their non-peptidyl mimetics in endocrinology: from synthesis to clinical perspectives. PMID- 9972683 TI - Low-dose midazolam attenuates predatory odor avoidance in rats. AB - Previous studies have shown that predatory odors are a potent anxiogenic stimulus for rodents, yet the ability of benzodiazepines to block odor-induced anxiety remains uncertain. The present study reevaluated this issue using a novel apparatus that, in contrast to previous studies, allowed rats to hide from the odor in a small wooden "hide box" placed within a larger arena. The odor stimulus used was a fabric cat collar that had been worn by a domestic cat for a period of 3 weeks. The experiment was divided into three phases on successive days: 1) habituation, where all rats were placed in the apparatus without cat odor present; 2) conditioning, where rats were presented with the cat odor in the apparatus; and 3) test, where rats previously exposed to the odor were tested for a conditioned avoidance response in the absence of the odor. Results showed that rats exposed to the cat collar displayed a robust avoidance response, spending about 70% of a 20-min session in the hide box compared to 25% in control rats. This avoidance response was completely reversed in rats given a low dose (0.375 mg/kg) of midazolam. During the test phase, rats exposed to the cat odor on the previous day showed elevated levels of hiding when returned to the test apparatus without the cat odor present. This conditioned avoidance was significantly attenuated in rats who had received midazolam (0.375 mg/kg) during cat odor exposure but not in rats given the same dose during the test. These results show that low-dose midazolam is an effective anxiolytic agent in rats during exposure to predatory odor. PMID- 9972684 TI - Altering dietary levels of protein or vitamins and minerals does not modify morphine-induced analgesia in male rats. AB - Previous research has demonstrated that chronic intake of nutritive sweet solutions, but not nonnutritive sweet solutions, enhances morphine's analgesic potency. To separate out the effects of sweet taste from other changes in dietary intake, which result when rats consume a sucrose solution, the effects of altering dietary levels of protein, or vitamins and minerals on morphine-induced analgesia were examined. In Experiment 1, 40 male Long-Evans rats were fed standard chow or a semipurified diet containing either 10, 20, or 40% protein. Three weeks later, antinociceptive responses to morphine were examined using the tail flick procedure. Tail flick latencies were measured immediately prior to and 30, 60, and 90 min after the administration of morphine sulfate (0.0, 1.25, 2.5, and 5.0 mg/kg, SC). At all three measurement times, antinociceptive responses increased directly as a function of the dose of morphine, but did not differ as a function of diet. In Experiment 2, 24 rats were maintained on either standard laboratory chow or semipurified diets containing 20% protein and either 100% or 25% of the recommended levels of vitamins and minerals for 3 weeks. Tail flick latencies were measured immediately prior to and 30 min after injections (SC) of 2.5 mg/kg morphine sulfate. This procedure was repeated until a cumulative dose of 10.0 mg/kg was obtained. Tail flick latencies increased significantly as a function of drug dose, but did not differ across dietary conditions. These results demonstrate that the increase in morphine-induced analgesia seen in rats consuming a sucrose solution is not due to alterations in either protein or micronutrient intake. PMID- 9972685 TI - Acute and chronic effects of morphine under a progressive-ratio 25 schedule of food delivery. AB - The present study examined the effects of morphine in pigeons responding under a progressive-ratio 25 schedule of food delivery. Morphine initially reduced response rates and breaking points. With chronic exposure, tolerance developed to these effects. The magnitude of the observed tolerance was not obviously different from that previously reported under a PR 5 schedule of food delivery. In addition, when drug effects were compared under the fixed-ratio 25 and fixed ratio 100 components comprised by the progressive-ratio schedule, comparable tolerance was observed. Although prior studies using other procedures have shown that ratio size modulates the development of tolerance to morphine and other drugs, the present data suggest that this relation is constrained, and is not easily observed under progressive-ratio schedules. PMID- 9972686 TI - Nicotine and ethanol interaction on conditioned taste aversions induced by both drugs. AB - The present study was designed to explore the interactive effects of nicotine and ethanol in the pretreatment and preexposure conditioned taste aversion (CTA) paradigm. The first experiment examined the effects of ethanol pretreatment on a nicotine induced CTA. The second experiment examined the effects of nicotine pretreatment on an ethanol CTA. The results of these two experiments revealed an asymmetrical interaction between ethanol and nicotine. Although nicotine pretreatment blocked an ethanol induced CTA, ethanol pretreatment merely attenuated a nicotine-induced CTA. These findings demonstrated that ethanol and nicotine interact pharmacologically in a unidirectional fashion, suggesting some unique and unshared pharmacological properties of each agent. The third experiment of this study examined the effects of preexposure with ethanol on a nicotine-induced CTA, while the fourth experiment examined the effects of preexposure with nicotine on an ethanol-induced CTA. These results revealed a symmetrical interaction between ethanol and nicotine in that both agents equally blocked CTA to one and the other. In contrast to the pretreatment CTA paradigm, these results suggested that both ethanol and nicotine appear to be functionally related and share common stimulus properties. Taken together, the present study demonstrates that while ethanol and nicotine are functionally related, they may also be endowed with unique unshared properties. PMID- 9972687 TI - Cortical damage enhances pemoline-induced self-injurious behavior in prepubertal rats. AB - Self-injurious behavior (SIB) is a devastating characteristic of several developmental disorders including a number of mental retardation syndromes. The functional neuroanatomy and neuropharmacology of SIB is not well understood. Self biting behavior (SBB) can be induced in rats by a high dose, systemic injection of pemoline (250 mg/kg, SC). This animal model allows for the investigation of anatomical and pharmacological aspects of SIB. Cortical pathology is a common occurrence in human disorders with SIB, and may be a fundamental pathological factor in producing the behavior. The present experiment was designed to investigate the effects of cortical damage on pemoline-induced SBB in prepubertal rats. Bilateral cortical aspirations were performed in 3-5-week-old rats. One week postsurgery, a pemoline challenge was administered. Behavioral comparisons were completed between the lesion group and an anesthetized-only control group. Results indicated that cortical damage significantly enhanced pemoline-induced SBB, along with some of the other pemoline-induced stereotypical behaviors. These results support the hypothesis that cortical damage influences the expression of stimulant-induced self-injury, and potential mechanisms for this influence are suggested. PMID- 9972689 TI - Destruction of the noradrenergic system with DSP4 potentiates the behavioral effects of MK-801 in rats. AB - In this study we investigated the effect of lesioning the noradrenergic systems on the behavioral effects of (5R, 10S)-(+)-5-Methyl-10,11-dihydro-5H-dibenzo [a, d] cyclohepten-5,10-imine hydrogen maleate--MK-801, in rats. The noradrenergic system was lesioned with N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine hydrochloride--DSP4 (60 mg/kg IP). MK-801 increased the locomotor activity and rearing. DSP4 significantly further increased the hyperlocomotor activity, circling (especially to the left side), sniffing, rolling, and falling that were induced by MK-801. These results showed that destruction of the noradrenergic system increased MK-801-hyperlocomotor activity, ataxia and stereotypy. PMID- 9972688 TI - The role of angiotensin II and of its receptor subtypes in the acetic acid induced abdominal constriction test. AB - The effects of angiotensin II (AngII), the AngII analogues saralasin--[Sar1, Ala8]AngII, sarmesin--[Sar1Tyr(Me)4]AngII, the nonpeptide AngII receptor antagonists DuP753 (losartan) (for AT1 receptor subtype) and PD123319 (for AT2 receptor subtype), as well as combinations of AngII and each of its analogues and receptor antagonists, administered intracerebroventricularly (ICV), were studied on mice using the acetic acid-induced abdominal constrictions test (acetic acid 1% intraperitoneally, IP). The abdominal constrictions were counted at 5-min intervals for 30 min. AngII at doses of 0.05, 0.1, and 1 microg exerted a dose dependent antinociceptive effect. Saralasin, sarmesin, losartan, and PD123319 exhibited a dose-dependent effect on nociception: they either increased or decreased it. PD123319 antagonized the antinociceptive effect of AnglI while losartan was ineffective. The importance of AT2 receptor subtype for the nociception reducing effect of AngII is considered. PMID- 9972690 TI - Cerebrolysin ameliorates performance deficits, and neuronal damage in apolipoprotein E-deficient mice. AB - Recent studies suggest that Cerebrolysin improves behavioral performance by affecting synaptic transmission in the hippocampus. The main objective of this study was to determine if Cerebrolysin administration ameliorates the neurodegenerative and performance deficits in aged apolipoprotein E (apoE) deficient mice. ApoE-deficient mice treated with Cerebrolysin showed a significant improved performance in the Morris water maze, compared to saline treated apoE-deficient mice. Although the improved performance in the Cerebrolysin-treated apoE-deficient mice was associated with restoration of the neuronal structure, the poor learning ability of saline-treated apoE-deficient mice was related to the a disrupted synaptodendritic structure. This study supports the contention that Cerebrolysin might have a neurotrophic effect in vivo. PMID- 9972691 TI - Modulation of cocaine-induced antinociception by opioid-receptor agonists. AB - Cocaine can produce antinociception in a number of animal models. The present experiments were designed to determine if opioid receptor agonists modulate cocaine-induced antinociception in rats. Cocaine produced a dose-dependent increase in antinociception in the hot-plate, but not paw-pressure, test. The combination of cocaine and morphine or [D-Pen2, D-Pen5]enkephalin (DPDPE) produced results no greater than simple additivity in the hot-plate test. However, the combination of cocaine and morphine produced greater antinociception than morphine alone in the paw-pressure test. A low dose of U69,593 potentiated the effects of cocaine in the hot-plate test. In contrast, cocaine attenuated the effect of U69,593 in the paw-pressure test. Both naltrexone and the selective kappa-opioid receptor antagonist nor-binaltorphamine (nor-BNI) blocked the potentiation of cocaine-induced antinociception by U69,593. The combination of U69,593 and cocaine can produce superadditive or subadditive effects, depending upon the doses and antinociceptive assay used. PMID- 9972692 TI - Neuronal sparing and behavioral effects of the antiapoptotic drug, (-)deprenyl, following kainic acid administration. AB - (-)Deprenyl is an irreversible inhibitor of monoamine oxidase B (MAO-B) frequently used as an adjunct therapy in the treatment of Parkinson's Disease. Recent evidence, however, has found that deprenyl's metabolites are associated with an antiapoptotic action within certain neuronal populations. Interestingly, deprenyl's antiapoptotic actions appear not to depend upon the inhibition of MAO B. Due to a paucity of information surrounding (-)deprenyl's ability to spare neurons in vivo, a series of studies was conducted to further investigate this phenomenon within an apoptotic neuronal death model: kainic acid induced excitotoxicity. Results indicated that (-)deprenyl increased hippocampal neuronal survival compared to saline-matched controls following kainic acid insult. Furthermore, it was discovered that (-)deprenyl treatment could be stopped 14 days following CNS insult by kainate, with evidence of neuronal sparing still present by day 28. In open-field locomotor activity testing of kainate-treated animals, those given subsequent (-)deprenyl treatment showed habituation curves similar to control subjects, while saline-treated animals did not. Given deprenyl's antiapoptotic actions, it is proposed that (-)deprenyl may be beneficial in the treatment of a variety of neurodegenerative diseases where evidence of apoptosis exists, such as Parkinson's and Alzheimer's Disease, by slowing the disease process itself. PMID- 9972693 TI - Electrical stimulation of nucleus paragigantocellularis induces opioid withdrawal like behaviors in the rat. AB - To examine a role for the medullary nucleus paragigantocellularis (PGi) in mediation of the symptomatology of opioid withdrawal, bilateral electrical stimulation of the PGi was performed in conscious, unrestrained, opioid naive (nondependent) rats. A characteristic series of behaviors was elicited during each 30-min session of PGi stimulation. The profile of these behaviors resembled qualitatively, but was not quantitatively identical with those seen during precipitated withdrawal from opioid dependence. This behavioral syndrome has been termed, opioid withdrawal-like behavior. The opioid withdrawal-like behaviors were voltage-, but not frequency-, dependent. Tolerance to repeated stimulation of the PGi did not develop following a series of 30-min runs of stimulation over 3.5 h. Intracerebroventricular (i.c.v.) injections of the nonselective opioid antagonist, naloxone, significantly decreased (by 40-50%) the intensity of stimulation-induced behavioral responses, as did injections of either the mu selective (beta-funaltrexamine, beta-FNA) or the delta-selective (naltrindole, NTI) opioid antagonists. In contrast, similar i.c.v. injections of the kappa selective antagonist, nor-binaltorphimine (nor-BNI), did not block behavioral responses to PGi stimulation. The results indicate that activation of the PGi by electrical stimulation can elicit behaviors similar to those observed during opioid withdrawal. Endogenous opioids, acting through mu- and delta-, but not kappa-opioid receptors, participate in mediating opioid withdrawal-like behaviors induced by PGi stimulation. PMID- 9972694 TI - Effects of nicotine and stress on startle amplitude and sensory gating depend on rat strain and sex. AB - We recently reported that 14 days of nicotine administration (12 mg/kg/day) reduced acoustic startle reflex amplitude and impaired prepulse inhibition (PPI) of startle in male and female Long-Evans rats. These findings contrasted with reports of nicotine-induced enhancement of startle and PPI in Sprague-Dawley (a different strain) male rats. The present experiment administered 0, 6, or 12 mg/kg/day nicotine via osmotic minipump for 14 days to 120 Sprague-Dawley rats (male and female) and to 120 Long-Evans rats (male and female) and examined ASR and PPI. Half of the subjects also were stressed by immobilization once each day to examine nicotine-stress interactions. Nicotine enhanced ASR and PPI responses of Sprague-Dawley rats but impaired these responses in Long-Evans rats, regardless of sex. Effects of stress were complex and depended on strain, sex, and drug dose. These findings indicate that effects of nicotine on measures of reactivity (ASR) and sensory gating (PPI) depend on genotype and that nicotine stress interactions depend on genotype, sex, and nicotine dosage. PMID- 9972695 TI - Acutely administered clozapine does not modify naloxone-induced withdrawal jumping in morphine-dependent mice. AB - A direct comparison of the effects of clozapine and haloperidol upon naloxone induced withdrawal jumping was investigated in morphine-dependent mice, as this syndrome may provide a behavioral baseline to differentiate between the two neuroleptics. Neither clozapine ((0.03-3.0 mg/kg s.c., n=9-10) nor haloperidol (0.01-04).1 mg/kg s.c., n=9-10) affected withdrawal jumping precipitated by 0.1 or 15.0 mg/kg i.p. naloxone in morphine-dependent mice. Measurement of locomotor activity immediately prior to naloxone administration revealed a dose-dependent reduction in activity by both compounds, indicating pharmacological effects at the time of naloxone-induced withdrawal. Clonidine (0.02-0.5 mg/kg s.c., n=9-10) also had no affect upon withdrawal jumping, although reductions in locomotor activity prior to naloxone administration were detected. There is no difference in the effects of acutely administered clozapine and haloperidol upon naloxone precipitated withdrawal jumping in morphine-dependent mice. PMID- 9972696 TI - Antinociceptive effects of cocaine in rhesus monkeys. AB - The antinociceptive effects of (-)cocaine, (+)cocaine, and cocaine methiodide administered alone and in combination with the mu-opioid agonist morphine were evaluated in rhesus monkeys. The shaved tails of four rhesus monkeys were exposed to warm water (42, 46, 50, and 54 degrees C), and tail-withdrawal latencies (20-s maximum) from each temperature were determined. (-)Cocaine (0.032-1.8 mg/kg, s.c.) produced dose-dependent antinociceptive effects and enhanced the antinociceptive effects of morphine. Neither (+)cocaine nor cocaine methiodide (0.1-10 mg/kg, s.c.) produced antinociception or altered the effects of morphine. Pretreatment with the serotonin receptor antagonist mianserin (0.1-04).32 mg/kg, i.m.) produced dose-dependent rightward shifts in the dose-effect curve for ( )cocaine alone, and attenuated (-)cocaine-induced enhancement of the antinociceptive effects of morphine. However, mianserin (0.32 mg/kg, i.m.) did not alter the antinociceptive effects of morphine alone. These results suggest that in rhesus monkeys, the effects of cocaine on nociception may be stereoselective and centrally mediated. These findings further suggest that the antinociceptive effects of cocaine in primates may be mediated at least in part by cocaine's effects on serotonergic systems. PMID- 9972697 TI - Intraaccumbens raclopride attenuates amphetamine-induced locomotion, but fails to prevent the response-reinstating properties of food reinforcement. AB - It has been well established that the presentation of a single reinforced trial in the midst of extinction results in a reinstatement of the previously reinforced operant response. In previous experiments, we have shown that systemically applied raclopride (a selective dopamine D2 receptor antagonist) dose dependently blocked the response-reinstating properties of food reinforcement, while SCH39166 (a selective dopamine D1 receptor antagonist) did not (11). The current experiments investigated the possible role of the nucleus accumbens in these actions of raclopride. In the first of two experiments, hungry rats were trained to traverse a straight runway for food reinforcement, a response that was then weakened through a series of extinction trials. On a single treatment trial, subjects were infused with one of three doses of intraaccumbens raclopride (0.0, 2.5, or 5.0 microg/0.5 microl/side) just prior to a reinforced trial. Twenty-four hours later, a single test trial was run in an unbaited runway. The results demonstrate that the prior day's reinforced trial produced a reinstatement of operant runway performance that was unaltered by intraaccumbens applications of raclopride. Two days later, the same animals were tested in a second experiment investigating the effects of intraaccumbens raclopride on amphetamine-induced locomotion. Subjects were pretreated with 1.0 mg/kg s.c. amphetamine prior to a 90-min locomotor activity session. The following day, subjects were again pretreated with amphetamine, but this time with a challenge dose of raclopride. Results demonstrate that the same raclopride doses that produced no effect in the response-reinstating experiment produced, in the same rats, a dose-dependent attenuation in amphetamine-induced locomotion. These data suggest that dopamine D2 receptors in the nucleus accumbens may not, in and of themselves, be necessary for the response-reinstating effects of food reinforcement. PMID- 9972698 TI - Chronic amphetamine facilitates immunosuppression in response to a novel aversive stimulus: reversal by haloperidol pretreatment. AB - The effect of chronic d-amphetamine sulfate (AMPH) treatment (nine daily injections, 2 mg/kg i.p.) on subsequent foot shock stress-induced immunological response was investigated. In addition, the potential role of a dopaminergic (DA) mechanism in the development of chronic AMPH-induced changes in stress-influenced immune responses was characterized. Exposure to foot shock stress decreased the percentage of T-lymphocytes, and reduced the delayed-type hypersensitivity reaction (DTH) in chronically AMPH-pretreated rats relative to vehicle-treated controls. Both of those stress-induced immunosuppressive responses were no longer evident when AMPH-pretreated rats were injected with haloperidol (HAL, 1 mg/kg i.p.) 30 min prior to each daily AMPH injection. The present findings are indicative of a modulatory role for dopamine in the facilitating process induced by AMPH on stress-induced immunosuppressive effects. PMID- 9972699 TI - Cyclic withdrawal from endogenous and exogenous progesterone increases kainic acid and perforant pathway induced seizures. AB - Antiseizure effects of progesterone (P) and its metabolite, 5alpha-pregnan-3alpha ol-20-one (3alpha, 5alpha-THP) were investigated following continuous vs. discontinuous P exposure. In Experiments 1, 32 cycling Long-Evans rats were administered kainic acid (32 mg/kg SC), ictal behavior was examined, and plasma 3alpha,5alpha-THP levels were measured by radioimmunoassay. Proestrus/estrus rats showed less ictal activity and had elevated 3alpha,5alpha-THP levels prior to kainic acid compared to diestrus/metestrus subjects. In Experiment 2, 49 ovariectomized (ovx) rats were SC injected with estradiol benzoate (EB; 10 microg) and P (500 microg), to mimic estrus, or sesame oil vehicle (0.2 cc); all subjects were administered kainic acid. Rats tested with EB+P showed a reduced mean duration of full seizures and increased 3alpha,5alpha-THP, whereas those tested 24 h following EB+P had more tonic clonic seizures and lower 3alpha,5alpha THP concentrations, comparable to ovx control animals. In Experiment 3, 49 ovx rats were stereotaxically implanted with bipolar electrodes into the perforant pathway. Prior to perforant pathway stimulation, rats received cholesterol or EB+P capsules for 1 month, continuously or intermittently. Irrespective of continuous or intermittent EB+P, the presence of progestins at the time of perforant pathway stimulation reduced partial seizure activity. Continuous EB+P capsules resulted in increased 3alpha,5alpha-THP levels compared to all other conditions, and less damage in the hilus of the hippocampus, compared to intermittent EB+P. These data confirm that P and 3alpha,5alpha-THP have antiseizure effects, and further suggest that repeated cycles of endogenous or exogenous P and/or 3alpha,5alpha-THP withdrawal influences seizure threshold and/or hippocampal integrity. PMID- 9972700 TI - Effects of SCH23390 and raclopride on anxiety-like behavior in rats tested in the black-white box. AB - Dopamine (DA) systems are activated by stress, and this response has as a corollary the induction of stress-related behaviors such as anxiety. In mice, D2 receptor blockade produces an apparent anxiogenic effect, although locomotor impairments might have been present. We investigated the effects of D1 and D2 antagonists on a variety of anxiety-like behaviors induced by the black-white box in rats and carefully screened for any locomotor deficits. Adult male Lister hooded rats were injected with either the D1 antagonist SCH23390 (0. 0.1. or 0.25 mg/kg i.p.) or the D2 antagonist raclopride (0, 0.05, or 0.10 mg/kg i.p.) 20 min prior to being placed into the white chamber of the black-white box (n = 8 10/group). Rats were videotaped and the tapes were scored for latency to exit the white chamber, latency to reenter the white chamber, time spent in the white chamber, intercompartmental crossing, and locomotor activity. ANOVA revealed no effect of the D1 antagonist SCH23390 on any behavioral measure. However, the raclopride-treated rats left the white area sooner than control rats (p < 0.01). Raclopride-treated rats also exhibited delayed reentry times to the white chamber compared to control rats (p < 0.01) and spent significantly less time in the white chamber (p < 0.05). Neither SCH23390 nor raclopride affected locomotor activity in a manner that confounded these behaviors. These results confirm that D2 receptor blockade enhances anxiety in rats tested in the black-white box. PMID- 9972701 TI - Behavior and drug measurements in Long-Evans and Sprague-Dawley rats after ethanol-cocaine exposure. AB - Long-Evans and Sprague-Dawley rats show differential behavioral responses to cocaethylene, a metabolite derived from the simultaneous ingestion of ethanol and cocaine. Such differences may also be manifested when these outbred strains are exposed to ethanol and cocaine. To test this hypothesis, both strains were fed an ethanol-diet (8.7% v/v) in conjunction with cocaine (15 mg/kg) injections for 15 days. The following parameters were evaluated: (a) ethanol consumption, (b) cocaine-induced behavioral activity, (c) blood ethanol levels, (d) blood, liver, or brain cocaine and cocaethylene levels, and (e) liver catalase and esterase activity. We found that Long-Evans rats drank significantly more of the ethanol diet relative to the Sprague-Dawley line during the first few days of the test session. This rat phenotype also differed significantly from the Sprague-Dawley line in terms of behavioral activity after cocaine administration. Blood ethanol levels did not differ between strains. Similarly, we failed to detect strain dependent differences in blood, liver, or brain cocaine levels as measured by gas chromatography/mass spectrometry. Cocaethylene levels, however, were higher in blood and brain of Long-Evans relative to Sprague-Dawley cohorts. Although the ethanol-cocaine regimen produced a marked suppression of catalase and esterase activity compared with control-fed rats, this suppression was roughly equivalent in both rat phenotypes. These data are discussed in the context of genotypic background and vulnerability to polysubstance abuse. PMID- 9972702 TI - Ontogeny of ethanol-induced locomotor activity and hypothermia differences in selectively bred FAST and SLOW mice. AB - The replicate lines of selectively bred FAST and SLOW mice differ in locomotor response to 2 g/kg ethanol (EtOH). FAST mice show enhanced locomotion; SLOW mice exhibit no change or locomotor depression. Little is known about the responses of FAST and SLOW mice to EtOH during development. We assessed the locomotor responses of FAST and SLOW mice at postnatal days (P) 10, 15, 30, and 60. A genetically correlated response, EtOH-induced hypothermia, was also investigated. Although all animals demonstrated their respective selection phenotypes in adulthood, developing FAST mice exhibited ethanol stimulation by P15 (replicate 1) or P30 (replicate 2). At these ages, responses of FAST mice differed from those of SLOW. The stimulant response in FAST mice was adult-like at P30. EtOH induced hypothermia was seen in SLOW mice by P15. These data suggest that sensitivity to the locomotor stimulant effects of EtOH changes during postnatal development, and may mirror developmental profiles for certain neurotransmitter systems. PMID- 9972703 TI - 3H-L-glutamate binding and 3H-D-aspartate release from hippocampal tissue during the development of pentylenetetrazole kindling in rats. AB - Previous studies have proposed that there is an increase in the density of glutamate binding sites after pentylenetetrazol (PTZ) kindling, whereas the glutamate release is not altered. Little is known about the time course of these changes. Therefore, we studied 3H-L-glutamate binding to hippocampal membranes and K+-stimulated 3H-D-aspartate release from hippocampal slices of rats given PTZ 3, 7, and 13 times up to a fully kindling state. After three PTZ injections, amino acid release from hippocampal tissue slices was significantly enhanced in comparison to controls, whereas 3H-L-glutamate binding was not altered. After seven injections of PTZ, specific glutamate binding to hippocampal membranes tended to increase, and K+-stimulated 3H-D-aspartate release from rat hippocampal slices was normalized. The kindled state characterized by generalized clonic tonic seizures was reached after 13 PTZ injections, and it was accompanied by an enhancement in the density of glutamate binding sites, whereas the chemically evoked amino acid release remained unchanged. It can be concluded that the amino acid release is increased in the early phase of PTZ kindling development, whereas after completion of kindling, the density of excitatory amino acid binding sites is enhanced. PMID- 9972704 TI - Latent inhibition in smokers vs. nonsmokers: interaction with number or intensity of preexposures? AB - Latent inhibition (LI) refers to the slowing of learning about a stimulus after preexposure, i.e., previous presentation of the stimulus without any consequence. This report summarizes results of four studies investigating the effect of being a smoker or nonsmoker on auditory LI as a function of procedural parameters, namely number (10 vs. 30) and intensity (low vs. high) of preexposed stimuli. In general, the number of preexposures did not affect LI, whereas low-intensity stimuli led to greater LI than high-intensity stimuli. These findings underline the importance of automatic vs. controlled processing of the preexposed stimuli for the development of human LI. Smokers showed increased LI compared to nonsmokers in low-intensity task versions as well as compared to both smokers and nonsmokers in high-intensity versions. These findings may indicate that nicotinic effects on LI depend on the robustness of LI in the control group. PMID- 9972705 TI - Ascorbic acid antagonizes ethanol-induced locomotor activity in the open-field. AB - It has been reported that ascorbic acid (AA) antagonizes the physiological and behavioral effects of dopamine (DA). AA reduces locomotor activity induced by dopaminergic agonist drugs. Also, AA amplifies the action of antidopaminergic drugs. Ethanol, like other drugs, produces a release of DA in the mesolimbic pathway, and at some doses, induces locomotor activity in mice. The ethanol induced locomotor activity could be dopamine-dependent because it can be reduced by antidopaminergic drugs. In the present study, we investigated whether an acute administration of AA reduces ethanol-induced locomotor behavior. AA, at doses (0.0, 21.85, 87.5, 175, 350. and 1400 mg/kg) was injected i.p. into mice, 0, 30, 60, or 90 min before an i.p. injection of ethanol (0.0, 0.8, 1.6, 2.4, and 3.2 g/kg). Locomotor activity was evaluated in open-field chambers. Our results showed that AA (350 and 1400 mg/kg) reduced ethanol-induced locomotor activity when injected 30 min before ethanol treatment. This effect was lost when ethanol was administered 90 min after AA injection. AA also reduced locomotor activity produced by d-amphetamine and methanol. The results support a pro-dopaminergic action of ethanol, and suggest a common dopaminergic pathway for the drugs of abuse in locomotor activity. PMID- 9972706 TI - Ontogeny of muscarinic cholinergic supersensitivity in the Flinders Sensitive Line rat. AB - The present study examined the ontogeny of muscarinic sensitivity in the Flinders Sensitive Line (FSL) rat, a model for human depression that was selectively bred for increased cholinergic function. In most cases, the FSL rats were more sensitive to the muscarinic agonists, oxotremorine and oxotremorine-M. early postnatally [13 days postpartum (P13)], suggesting that muscarinic supersensitivity is an inherent characteristic of FSL rats. The emergence of increased sensitivity to muscarinic agonists in FSL rats did not correlate with either the emergence of subsensitivity to the muscarinic antagonist, scopolamine, at P60 or with increased muscarinic (M1 or M2) receptor density. Relative to FRL rats, FSL rats did not exhibit increases in muscarinic receptor binding until P32 in the striatum and hippocampus and P120 in the hypothalamus. These results are consistent with the suggestions that (a) muscarinic supersensitivity, which appears early in development, may be associated with depressive disorders, and (b) the differences in muscarinic sensitivity early postnatally cannot be accounted for by an increase in the number of muscarinic receptors, per se. PMID- 9972708 TI - The effects of acute and repeated pyridostigmine bromide administration on response acquisition with immediate and delayed reinforcement. AB - This experiment was designed to assess the effects of acute and repeated administration of pyridostigmine bromide (a carbamate with prophylactic and therapeutic uses) on response acquisition. Experimentally naive, male Sprague Dawley rats were exposed to a situation in which lever presses were either immediately followed by food-pellet presentation or after a 16-s resetting delay. Different groups of rats received either one acute administration of pyridostigmine bromide (10 mg/kg, by gavage) or repeated pyridostigmine administration for 7 days (1.5 mg/kg/day, by gavage). Other groups were treated with distilled water for the same period of time. Both acute and repeated pyridostigmine bromide administration decreased serum cholinesterase levels by approximately 50%, but neither treatment affected brain cholinesterase levels in our assay. Acute and repeated drug administration produced the same behavioral effects. Subjects exposed to the 0-s delay conditions obtained many more food pellets than those exposed to the 16-s delay conditions. Administration of pyridostigmine bromide delayed the onset of responding in some, but not all, of the subjects in the treated groups, independent of the delay condition to which they were exposed. Many more responses were observed on an inoperative lever during the 16-s delay conditions than during the 0-s delay conditions, especially during the 16-s delay condition in which subjects had received acute vehicle administration. Whether or not these effects of small doses of pyridostigmine bromide on response acquisition are of central or peripheral origin will need to be determined in future studies, as response acquisition in the present experiment may have been affected by pyridostigmine's effects on gastrointestinal functioning and/or motor activity. PMID- 9972707 TI - Involvement of intracellular calcium in morphine tolerance in mice. AB - Opioid analgesic tolerance is associated with a disruption in Ca++ homeostasis. Drugs reducing Ca++ influx can prevent and reverse tolerance. The hypothesis was tested that both Ca++ influx and mobilization from intracellular pools maintains the expression of morphine tolerance. Ca++ modulating drugs were injected ICV at doses not affecting morphine's potency in placebo pellet-implanted mice, in order to determine whether tolerance would be reversed in morphine pellet-implanted mice. The Ca++ chelator EGTA significantly reversed tolerance. The Ca++ channel antagonists nifedipine and omega-conotoxin GVIA also reversed tolerance. The role of intracellular Ca++ was investigated using the membrane permeable intracellular Ca++ chelator EGTA-AM. EGTA-AM reversed tolerance at lower morphine doses, but not at higher morphine doses. Thus, mobilization of intracellular Ca++ contributes to the expression of tolerance. Finally, 1,4-dihydropyridine sensitive Ca++ channels are known to stimulate Ca++-induced Ca++ release (CICR) from Ca++/caffeine-sensitive microsomal pools possessing ryanodine receptors. We examined whether blocking Ca++ mobilization from these pools with ryanodine would reverse morphine tolerance. Ryanodine's effects were similar to EGTA-AM. Tolerance was reversed at lower morphine doses, but not at higher doses. Thus, morphine tolerance appears to be associated with increases in Ca++ influx and mobilization from Ca++/caffeine-sensitive pools. PMID- 9972709 TI - Stress and a glycinergic intervention interact in the modulation of MK-801 elicited mouse popping behavior. AB - The ability of D-cycloserine, a partial glycine agonist, to modulate mouse popping behavior elicited by MK-801, a noncompetitive NMDA receptor antagonist, was studied in unstressed and stressed mice. In unstressed animals, D-cycloserine (5.6 and 10 mg/kg) attenuated the ability of MK-801 (1.0 mg/kg) to elicit this behavior. However, the ability of D-cycloserine to attenuate MK-801-elicited mouse-popping behavior was not evident in stressed mice, 24 h after they were forced to swim for up to 10 min in cold water. Thus, the therapeutic value of glycinergic interventions may be limited by environmental factors, such as stress. PMID- 9972710 TI - The history of the Southeastern Society of Plastic and Reconstructive Surgeons. PMID- 9972711 TI - Prevention of unfavorable scars using early pulse dye laser treatments: a preliminary report. AB - Hypertrophic scarring occurs frequently in the trunk and extremities, and sporadically in other areas even under favorable circumstances. Unfortunately, the existing methods of scar manipulation have not been effective in preventing these unfavorable scars. Established hypertrophic scars have been treated by Anderson and Parrish, Alster, and others using the 585-nm pulse dye laser. The current study is the first report of prevention of hypertrophic scarring using the 585-nm pulse dye laser in a large group of elective and traumatic incisions. Treatment within the first few weeks resulted in faster resolution of scar stiffness and erythema, and less frequent development of hypertrophic scarring. An unexpected finding was the substantial improvement in the quality of scarring in all areas of the body, attributed to the excellent color match of the treated scars. These observations suggest that early pulse dye laser treatments can change fundamentally the physiology of wound healing if applied in the early phases. This report provides the first clinical correlation between prophylactic laser reduction of scar microcirculation and prevention of excessive scar formation. PMID- 9972712 TI - 35 mm film vs. digital photography for patient documentation: is it time to change? AB - 35 mm photography is currently the standard method of documenting a patient's appearance and recording the post-operative changes. With rapidly advancing technology, the digital system is now capable of providing vivid pictures that have multiple advantages over conventional 35 mm photography. Namely, digital pictures are comparatively inexpensive to take, can be stored as digital information, easily retrieved, and immediate viewing and imaging are possible. For many applications in plastic surgery patient documentation, digital photography is now more affordable and flexible than the 35 mm film system. The following is a cost and quality comparison between the two systems. PMID- 9972713 TI - Combination therapy: utilization of CO2 and Erbium:YAG lasers for skin resurfacing. AB - Skin resurfacing with carbon dioxide (CO2) lasers is a commonly used method for skin rejuvenation. With these lasers, there is substantial skin improvement with lessening of rhytids and skin discoloration, and noticeable skin tightening. However, there is also significant morbidity associated with their use. To decrease the healing and erythema times, other types of lasers have been developed. The author discusses the practice of combining the CO2 and Erbium:YAG lasers for limiting thermal injury. For deeper rhytids in the periorbital, perioral, and forehead regions, multiple passes with the CO2 laser are often the preferred treatment. For moderate rhytids, the CO2 laser can be used for the first pass followed by one to multiple passes with the Erbium:YAG laser. Erbium:YAG lasers when used alone are beneficial for removing fine wrinkles and discolorations. Combining these lasers results in both rhytid improvement and decreased morbidity. PMID- 9972714 TI - The mastectomy specimen as a model for TRAM flap fabrication in immediate breast reconstruction. AB - Traditionally, most of transverse rectus abdominis musculocutaneous (TRAM) flap shaping takes place after transfer of the flap to the chest. As skin-sparing mastectomies become more commonplace, flap tailoring becomes a more difficult and lengthy process due to lack of exposure through these small incisions. Immediate breast reconstruction was performed on 40 patients using the mastectomy specimen as a model for TRAM flap fabrication. Detailed measurements of the specimen were taken and a template was created as a guide for shaping the flap. All flaps were shaped on the abdomen, and additional tailoring was not necessary after transfer to the chest. Significant differences in weight were recorded between the shaped flap and the specimen. Size, shape, and orientation were found to be more reliable parameters in matching the flap to the specimen than approximating their weights. This approach allows for greater accuracy in shaping the flap, reduces operative time, and avoids flap manipulation after transfer. PMID- 9972715 TI - Wound complications of abdominoplasty in obese patients. AB - The records of 90 patients who underwent an abdominoplasty at the University of Virginia Health Sciences Center were analyzed to determine the effect of obesity on the incidence of complications after this surgery. The study patients were divided into three groups-obese, borderline, and nonobese-based on the degree to which their preoperative weights varied from their ideal body weight. A history of previous bariatric surgery was also analyzed to determine what impact that might have on subsequent abdominoplasty. Results showed that 80% of obese patients had complications compared with the borderline and nonobese patients, who had complication rates of 33% and 32.5% respectively (p = 0.001). Previous gastric bypass surgery had no significant effect on the incidence of postabdominoplasty complications. Based on these findings the authors conclude that obesity at the time of abdominoplasty has a profound influence on the wound complication rate following surgery, regardless of any previous weight reduction surgery. PMID- 9972716 TI - Functional outcomes of microsurgical reconstruction of delayed complications following head and neck cancer ablation. AB - Treatment of large and/or invasive head and neck cancers results in defects that are complex, such that immediate free tissue transfer provides the best functional outcomes. Consequently, delayed use of free flaps in such patients is seldom seen in today's practice. The purpose of this study was to analyze a recent experience of such delayed microsurgical procedures to evaluate their efficacy and outcomes. Between November 1995 and May 1997, 13 patients underwent free flap reconstruction of residual or secondary defects following initial head and neck cancer ablation. Preoperative status was categorized as open wounds in 8 patients, oral incontinence in 9 patients, poor speech in 5 patients, and difficulty swallowing in 7 patients. Microvascular reconstruction was performed for the mandible and floor of the mouth/chin in 7 patients, cervical esophagus in 2 patients, sinus cavity in 2 patients, and one patient each underwent microvascular reconstruction of the orbit and cranial base. The free flaps utilized were fibular osteocutaneous (N = 6), radial forearm fasciocutaneous (N = 2), rectus abdominis (N = 2), jejunum (N = 1), radial forearm osteocutaneous (N = 1), and serratus (N = 1). There were no flap failures and the overall complication rate was 62%. Functional outcomes were best for the static conditions of open wound and oral incontinence, each demonstrating a 75% and 78% substantial improvement respectively. Conversely, functional improvement in dynamic functions such as poor speech and difficulty swallowing fared less well. Only 60% of patients with poor speech and 14% with difficulty swallowing showed significant improvement despite aggressive speech and swallowing therapy. These data show that the functional outcomes of free flap reconstruction of delayed head and neck cancer complications are inferior to those expected with immediate reconstruction using free tissue transfer. Nevertheless, reconstruction can be very useful with a high likelihood of flap survival and patient improvement. PMID- 9972717 TI - A new technique for the treatment of flexor digitorum profundus tendon avulsion. AB - Current treatment of flexor digitorum profundus (FDP) avulsion with complex external wire or button fixation is associated with significant morbidity. A new method of internal fixation avoids the complications that are associated with previous techniques. Through a volar Bruner incision, the profundus tendon is retrieved. A transverse dorsal incision is made and two holes are drilled. A double-arm suture is passed through the tendon and bone, and is tied dorsally. Both incisions are closed, leaving the repair entirely internal. This simple technique produces a solid reinsertion of the FDP tendon and avoids damage to the nail bed and matrix. Internal fixation eliminates nail plate deformities, reduces cost, speeds recovery, and produces a stable reconstruction. PMID- 9972718 TI - Clinical application of a nonpenetrating microvascular stapling device for vascularized free tissue transfer. AB - It is essential to develop a method that is technically easier and faster to perform microvascular anastomosis. Therefore the authors have utilized a nonpenetrating microvascular stapling device (VCS; Auto Suture, Tokyo, Japan). Eight vascularized free tissue transfers were performed using this stapling device. All of the transferred tissues were grafted successfully. The time required to perform the stapled microvascular anastomosis ranged from 8 to 18 minutes (mean, 12 minutes). Two arterial anastomoses required suture repairs because they could not be repaired with the use of this stapling device due to thickened vessel walls and intimal dissections. The microvascular stapling device proved useful for vascularized free tissue transfers, but the vessels suitable for this technique should be chosen carefully. Not only the surgeon but also the assistant must be experienced in microscopic surgery. PMID- 9972719 TI - Predictors of patient satisfaction in an outpatient plastic surgery clinic. AB - Although outcome measurement in medical care has traditionally included various aspects of clinical and functional status, patient satisfaction is another important metric in the assessment of health care quality. Determining which factors contribute most to patient satisfaction can assist health care providers in improving care. In an era of diminishing resources, satisfaction ratings can further aid third-party payers in determining who provides those services. The authors used the ordinal logistic regression method to develop a predictive model for patient satisfaction in an outpatient plastic surgery clinic. Consecutive patients who attended a university outpatient plastic surgery clinic were asked to complete the Visit Specific Patient Satisfaction Questionnaire (VSQ) after their clinic visit. Type of clinic (e.g., hand clinic, aesthetic clinic, breast clinic) and demographic variables like age, gender, race, and education were added to the questionnaire to control for possible confounding effects. The authors constructed an ordinal logistic regression model using the overall visit response as the dependent variable and the eight other response categories as independent variables. A total of 345 patients completed the VSQ, which takes each patient less than 2 minutes to complete. The patient response rate was more than 95%. Statistically significant predictors included (1) personal manner of physician (odds ratio [OR], 18.0; p = 0.0002), (2) time spent with physician (OR, 4.7; p = 0.0099), (3) length of time to get an appointment (OR, 4.6; p = 0.0055), and (4) explanation of what was done (OR, 3.9; p = 0.0263). There was no statistically significant association between overall satisfaction scores and the following factors: (1) length of wait in the clinic (OR, 2.7; p = 0.0747), (2) getting through to the clinic by phone (OR, 0.71; p = 0.5439), (3) convenience of the clinic's location (OR, 2.3; p = 0.1368), and (4) technical skills of the physician (OR, 1.0; p = 0.9974). The predictive model was adjusted for possible confounding due to the type of clinic and demographic variables. In this study the most important predictors of patient satisfaction were those related to efficient clinic operation (scheduling of appointments and clinic waiting time) and the quality of the patient-physician interaction. Clinic facilities (like clinic location and ease of phone contact) were not significant predictors. Because patients often have difficulty assessing the technical skills of physicians, this variable was not a significant predictor. To improve patient satisfaction in plastic surgery outpatient clinics, efforts and resources should be directed toward expedient and empathic delivery of care. PMID- 9972720 TI - Helical crus reconstruction using a postauricular chondrocutaneous flap. AB - The authors describe a helical crus reconstruction technique using a postauricular chondrocutaneous flap vascularized by the postauricular vessels. They used this procedure on 7 patients who had developed a large defect on the helical crus following surgery. In each patient the flap design was adjusted to fit the form of the defect. All flaps were in easy reach of the defect and all flaps survived without any complications. The reconstructed ears had good three dimensional form, and the color and texture match was satisfactory. The flap donor site was not noticeable because it was hidden behind the ear. Constriction did not occur and a good form was maintained. Neither deformity due to scar contracture nor absorption of the cartilage was observed. PMID- 9972721 TI - Autologous latissimus breast reconstruction in association with the abdominal advancement flap: a new refinement in breast reconstruction. AB - The authors present a technique that combines autologous latissimus breast reconstruction with the thoracoabdominal advancement flap. The aim is to reduce the patched effect of the dorsal skin paddle and to minimize scars on the reconstructed breast. Fifty patients underwent delayed breast reconstruction using this technique from March 1993 through May 1997. Of these 50 patients, 42 (84%) had unilateral reconstruction and 8 (16%) had two-stage bilateral reconstruction at 5- to 7-month intervals. Forty-one patients (82%) had previously received radiotherapy of the thoracic wall. The abdominal advancement flap allowed subtotal burial of the latissimus dorsi flap (preserving only the future nipple-areolar complex) in 40 patients (80%) and total burial in 10 patients (20%). Reduction surgery was done on the other breast in 17 patients (34%) and mastopexy in 3 patients (6%). In 8 patients (16%) the opposite breast required mastectomy and reconstruction using an autologous latissimus dorsi flap. The aesthetic results, as evaluated by two plastic surgeons on the basis of pre- and postoperative photographs, were rated as very good in 44 patients (88%), good in 5 patients (10%), and poor in 1 patient (2%). No result was considered bad. The main drawback was dorsal seroma, which occurred in 68% of patients but was managed easily by repeated aspiration. Subtotal or total burial of the skin paddle through the original association of the autologous latissimus dorsi flap with the abdominal advancement flap gives markedly improved results by reducing the scars on the reconstructed breast, avoiding the patched effect, and providing a supple breast with a natural ptotic shape. PMID- 9972722 TI - Callotasis in a fasciosteal flap model in rabbits: part II. a new contribution to the concept of distraction osteogenesis. AB - The basis of lengthening bones at their anatomic locations has been defined in detail by many authors. The possibility of distraction osteogenesis in vascularized bone grafts and the role of periosteum was investigated in 35 growing New Zealand White rabbits in four experimental groups: group 1, the scintigraphic assessment group (N = 4); group 2, the distraction group with intact periosteum (N = 15); group 3, the control group without periosteum in the distraction area (N = 6); and group 4, the control group in which the flaps were wrapped in silicone leaves (N = 10). Scintigraphy was used to evaluate the survival of the bone graft. Metatarsal fasciosteal flaps were fixed by external fixators and then subjected to osteotomy. Distraction was started after 10 days of osteotomy and continued at 0.5 mm/24 hr for 10 days, with a total elongation of 4 to 6 mm. Radiological examination at day 10 of starting the distraction, and both radiological and histological examinations at days 15, 20, and 30 were performed. In group 1, positive scintigraphic images of the flaps were obtained. In group 2, progressive calcification was detected radiologically and mixed-type ossification was observed histologically. However, in group 3, distraction failed. Group 4 was excluded from the study due to silicone exposition. The authors demonstrated that vascularized bone segments can be lengthened, and provided information about the importance of periosteum in distraction osteogenesis. PMID- 9972723 TI - Bipedicled submental island flap for upper lip reconstruction. AB - A case of reconstruction of the upper lip with a bipedicled submental flap is described. Although the mobility of the flap was restricted, the arterial blood supply was abundant by altering the single-pedicled flap into a bipedicled flap. This flap is a good color and texture match to the face, and surpasses other flaps in reconstruction of the mustache or beard in male patients. PMID- 9972724 TI - Surgical treatment for greater sphenoid wing fracture (orbital blow-in fracture). AB - The authors present 2 patients with greater sphenoid wing fractures that were treated surgically. This type of fracture is classified as a blow-in fracture of the lateral orbital wall. The first patient was a 16-year-old boy who was involved in a motor vehicle accident. Computed tomography (CT) disclosed a medial displacement of the inner wall of the greater sphenoid wing of the left orbit. He was unconscious for 3 days. After he recovered consciousness, he presented limited abduction of the left eye with diplopia in all gaze directions and mild left proptosis. Although these symptoms did not improve for 1 week, displaced bone fragments of the greater sphenoid wing were removed via the lateral orbital approach. The patient had a good postoperative course with progressive improvement in eye movement over the next several weeks. The second patient was a 22-year-old man whose face was hit in a fight. CT disclosed medial displacement of the inner wall of the greater sphenoid wing of the left orbit. Although the patient also presented limited abduction of the left eye on admission, this symptom improved gradually. However, diplopia in all gaze directions and mild left proptosis did not improve. Therefore, the displaced inner wall of the greater sphenoid wing was reduced via the lateral orbital approach. The patient showed a good postoperative course with progressive improvement over the next several weeks. This type of orbital fracture, which is classified as an orbital blow-in fracture, is relatively rare. This type of greater sphenoid wing fracture is caused by buckling of the orbital wall secondary to severe compression of the orbital rim. Surgical treatment using the lateral orbital approach through a hemicoronal skin incision afforded a wider operative field and better cosmetic result. PMID- 9972725 TI - Retrograde intra-arterial infusion of prostaglandin E1 and heparin for the no reflow phenomenon after oromandibular reconstruction with a free fibular flap. AB - The authors encountered a patient with a tumor of the floor of the mouth in whom the no-reflow phenomenon occurred after excision of the lesion and the mandible, followed by reconstruction using a free fibular flap. A catheter was inserted retrogradely from the point where the peroneal artery had been ligated at the time of flap preparation. Continuous intra-arterial infusion of prostaglandin E1 and heparin was performed, and the flap survived. This method salvaged free flaps subject to the no-reflow phenomenon. PMID- 9972726 TI - Malignant triton tumor of the maxilla: a patient report. AB - Malignant Triton tumor (or malignant schwannoma with rhabdomyoblastic differentiation) is a rare entity with a very poor prognosis. This is the second report of this type of rare and aggressive sarcoma arising in the maxilla. The clinical course, therapeutic approach, and histopathological aspects of the case are presented. PMID- 9972727 TI - Chondroid syringoma of the orbit. AB - Chondroid syringoma is a rare subcutaneous tumor that mainly affects the face and the neck. The authors present an occurrence in the orbit, which they believe to be the first reported at that site. Computed tomography and magnetic resonance imaging suggested that the tumor had invaded the globe, but at surgery the mass was well circumscribed and did not invade or adhere to other structures. The tumor was resected easily under general anesthesia. Epithelial cells of characteristic appearance within a chondroid matrix were demonstrated histologically. No recurrence has been evident in more than 1 year of follow-up. Most chondroid syringomas are benign, but because several cases have exhibited malignant behavior, periodic observation following complete resection is required. PMID- 9972728 TI - The intra-areolar incision for breast augmentation. AB - An intra-areolar approach for breast augmentation is described. A circumferential incision is made around the nipple, and the surrounding areola undermined. Although the resultant incision is small, it is possible to insert a tightly folded implant into the submuscular or subglandular plane. The resultant scar is camouflaged at the nipple-areolar junction, becoming virtually imperceptible. PMID- 9972729 TI - Reduction mammaplasty-the schnur sliding scale revisited. PMID- 9972730 TI - Upper lip flap for restoration of nasal lining in full-thickness nasal defects. PMID- 9972731 TI - Re: Endometrioma of the abdominal wall following combined abdominoplasty and hysterectomy: case report and review of the literature. PMID- 9972732 TI - Perioperative information and parental anxiety: the next generation. PMID- 9972733 TI - Epidural steroids in treating failed back surgery syndrome. PMID- 9972734 TI - Temperature monitoring and management during neuraxial anesthesia. PMID- 9972735 TI - Use of a preanesthetic video for facilitation of parental education and anxiolysis before pediatric ambulatory surgery. AB - In this study, we evaluated the effects of viewing an educational videotape about pediatric anesthesia on measures of parental knowledge of anesthesia and preoperative anxiety using a randomized, controlled design. During their routine preoperative visit, 85 parents of children scheduled to undergo ambulatory surgical procedures under general anesthesia were randomized to view either the experimental videotape about pediatric anesthesia or a control videotape with no medical content. Before and immediately after viewing the assigned videotape, parents completed measures of situational anxiety (State-Trait Anxiety Inventory State), preoperative anxiety and need for information (Amsterdam Preoperative Anxiety and Information Scale), and anesthesia knowledge (Standard Anesthesia Learning Test). Repeated-measures analyses of variance showed that parents who viewed the experimental videotape showed a significant increase in anesthesia knowledge (P < 0.022) and a significant reduction in their state of anxiety (P < 0.031), anesthesia-specific anxiety, and need for information (P < 0.0001) compared with the control group. These results demonstrated that viewing a preoperative educational videotape about pediatric anesthesia can provide immediate educational and anxiolytic benefits for parents of children undergoing ambulatory surgery. The duration of these benefits remains to be determined. IMPLICATIONS: In this study, we demonstrated the benefits of viewing an educational videotape about pediatric anesthesia on measures of parental knowledge of anesthesia and preoperative anxiety using a randomized, controlled design. We found that videotape viewing facilitated preoperative preparation and lessened preoperative anxiety. PMID- 9972736 TI - Validation of measures of parents' preoperative anxiety and anesthesia knowledge. AB - Parents' anxiety about their children's anesthesia may adversely affect the children's outcomes and compromise the quality of informed consent. Studies of these issues have been limited by the lack of validated measures of parental anxiety and knowledge surrounding anesthesia. In the present study, we evaluated psychometric properties of the Amsterdam Preoperative Anxiety and Information Scale (APAIS) and the Standard Anesthesia Learning Test (SALT) among 85 parents who participated in an evaluation of the effects of a videotape about pediatric anesthesia. The results supported the internal consistency, test-retest reliability, and concurrent validity of both instruments and documented the equivalence of two forms of the SALT. Factor analysis supported the previously demonstrated factor structure of the APAIS, further confirming its construct validity. We conclude that the APAIS and SALT are reliable and valid measures of parental anxiety and knowledge of pediatric anesthesia that can be used for clinical and research purposes. IMPLICATIONS: This study verified the reliability and validity of two questionnaires for measuring parents' knowledge and anxiety about pediatric anesthesia. These questionnaires can be used in further research on factors affecting parental anxiety and knowledge before their children's surgery. PMID- 9972737 TI - Platelet hyporeactivity in young infants during cardiopulmonary bypass. AB - Platelet dysfunction is one of the most important factors contributing to a postoperative hemorrhagic diathesis in children with congenital heart disease undergoing operations requiring cardiopulmonary bypass (CPB). However, very little is known about the influence of CPB on platelets in neonates and young infants. We studied 16 patients--8 young infants (<2 mo old) and 8 children (>12 mo old)--with congenital heart disease undergoing CPB. Surface density of an important platelet adhesive receptor, glycoprotein Ib, and degree of platelet activation, indicated by p-selectin positivity, were measured by whole blood flow cytometry in samples obtained at seven time points during the operations. We found that the percentage of p-selectin-positive platelets increased significantly in children, but not in young infants, during CPB. The young infant group exhibited a significantly smaller reduction of glycoprotein Ib than the child group during CPB (21.0% +/- 12.0% vs 32.7% +/- 18.1%; P < 0.05). Lack of CPB-induced increase of p-selectin and a smaller decrease of glycoprotein Ib in young infants in the current study suggest reduced platelet reactivity in young infants and neonates during CPB. The clinical significance of the reduced platelet reactivity in young infants and neonates remains to be determined. IMPLICATIONS: Platelets of young infants are less reactive than those of children during cardiopulmonary bypass, as determined by the cardiopulmonary bypass induced alterations in platelet membrane adhesive receptors. PMID- 9972738 TI - The effect of halothane on the amplitude and frequency characteristics of heart sounds in children. AB - Although continuous auscultation has been used during surgery as a monitor of cardiac function for many years, the effect of anesthetics on heart sounds has never been quantified. We determined the root mean squared amplitude and frequency characteristics (peak frequency, spectral edge, and power ratios) of the first (S1) and second (S2) heart sounds in 19 healthy children during induction of anesthesia with halothane. In all patients, halothane decreased the amplitude of S1 (R2 = 0.87 +/- 0.12) and S2 (R2 = 0.66 +/- 0.33) and the high frequency components (>80 Hz) of these sounds. These changes were clearly audible and preceded decreases in heart rate and blood pressure. The spectral edge decreased for S1 in 18 patients (R2 = 0.73 +/- 0.24) and for S2 in 13 patients (R2 = 0.58 +/- 0.25). Peak frequency did not change. The rapidity with which myocardial depression and its associated changes in heart sound characteristics occurred confirms that continuous auscultation of heart sounds is a useful clinical tool for hemodynamic monitoring of anesthetized infants and children. IMPLICATIONS: Heart sound characteristics can be used to monitor cardiac function during halothane anesthesia in children. The changes occur rapidly and precede noticeable changes in heart rate and blood pressure. PMID- 9972739 TI - Endobronchial intubation causes an immediate increase in peak inflation pressure in pediatric patients. AB - Our purpose was to determine whether endobronchial intubation always causes an immediate increase in peak inflation pressure and, if so, the magnitude of the increase. Fourteen children scheduled for central line placement for prolonged antibiotic administration comprised the study group. After routine premedication and induction of anesthesia (halothane in oxygen), an endotracheal tube was inserted, and its position was verified by auscultation and fluoroscopy. Children were mechanically ventilated using a preset volume pressure-limited ventilator with a 5-L fresh gas flow. All children received a constant tidal volume using a similar circuit, similar tubing, and a similar compression volume. The lowest peak inflation pressure to deliver a tidal volume of 15 mL/kg was used. After adjusting the respiratory rate (end-tidal CO2 30 mm Hg) and anesthetic level (halothane end-tidal 1.2%), the peak inflation pressure at this endotracheal position was recorded. The endotracheal tube was advanced into a bronchus, the position was verified as above, and peak inflation pressure was recorded. The endobronchial tube was then pulled back into the trachea, and placement of the central line proceeded. The peak inflation pressure at the endobronchial position was significantly greater than the peak inflation pressure at the endotracheal position (P < 0.0001). The increase was instantaneous at the endobronchial position. Monitoring peak inflation pressure while inserting an endotracheal tube and during anesthesia can help to diagnose endobronchial intubation. IMPLICATIONS: Monitoring peak inflation pressure while inserting an endotracheal tube and during anesthesia can help to diagnose endobronchial intubation. PMID- 9972740 TI - The effect of nitroglycerin on pacing-induced changes in myocardial oxygen consumption and metabolic coronary vasodilation in patients with coronary artery disease. AB - In the present study, we assessed the potential effect of nitroglycerin IV (NTG), a donor of exogenous nitric oxide, on metabolic coronary flow control in patients with coronary artery disease. In 12 patients scheduled for coronary artery surgery, arterial blood pressure, pulmonary capillary wedge pressure, coronary sinus blood flow (continuous thermodilution), myocardial oxygen supply (DVO2), and myocardial oxygen consumption (MVO2) were measured at sinus rhythm and in response to atrial pacing at 30 bpm greater than baseline sinus rate. These measurements were repeated during infusion of NTG 1 and 2 microg x kg(-1) x min( 1). At control, in the absence of NTG, MVO2 increased from 13.7 +/- 3.4 mL O2/min during sinus rhythm to 19.3 +/- 5.5 mL O2/min during pacing. NTG 1 and 2 microg x kg(-1) x min(-1) blunted the pacing-induced increase in MVO2 dose-dependently. During NTG 1 microg x kg(-1) x min(-1), MVO2 increased from 12.9 +/- 3.3 mL O2/min at sinus rhythm to 17.3 +/- 4.7 mL O2/min during pacing (P = 0.01 versus control pacing); during NTG 2 microg x kg(-1) x min(-1), MVO2 increased from 13.4 +/- 3.3 mL O2/min to 15.9 +/- 3.7 mL O2/min (P = 0.008 versus control pacing). However, the pacing-induced increase in DVO2 per mL O2/min increase in MVO2 (delta DVO2/delta MVO2), was significantly greater during the infusion of NTG 2 microg x kg(-1) x min(-1) (1.85 +/- 0.56; P = 0.023) compared with control (1.51 +/- 0.22). This was associated with an increase in coronary sinus hemoglobin oxygen saturation (30% +/- 5% at control pacing and 34% +/- 6% during pacing with NTG 2 microg x kg(-1) x min(-1); P = 0.018), which indicates that during the infusion of NTG, there was more metabolic coronary vasodilation than achievable solely on the basis of the metabolic stimulus. IMPLICATIONS: Our findings suggest that nitroglycerin, a donor of exogenous nitric oxide, reduces pacing-induced increases in myocardial oxygen consumption and enhances metabolic coronary vasodilation in patients with coronary artery disease, in whom endogenous nitric oxide activity may be reduced. PMID- 9972741 TI - Atrial natriuretic peptide attenuates pacing-induced myocardial ischemia during general anesthesia in patients with coronary artery disease. AB - Atrial natriuretic peptide (ANP) exerts a dilatory effect on coronary arteries in humans. We investigated the effects of ANP on pacing-induced myocardial ischemia during enflurane anesthesia in patients with coronary artery disease (CAD). In 20 patients with CAD, myocardial ischemia was induced by atrial pacing before and after an i.v. infusion of ANP (50 mg x kg(-1) min(-1), n = 10) or placebo (n = 10). We studied the effects of ANP or placebo on pacing-induced changes in central hemodynamics, myocardial blood flow and regional myocardial indices of lactate uptake (RMLU), and oxygen consumption (RMVO2) and extraction (RMO2E). ST segment depression was less pronounced during pacing with ANP compared with control pacing (-0.09 +/- 0.01 vs -0.24 +/- 0.02 mV; P < 0.001). RMLU decreased to -11.1 micromol/min during control pacing compared with -0.7 micromol/min during pacing with ANP (P < 0.01). ANP did not affect pacing-induced changes in RMVO2, RMO2E, or the rate pressure product. Placebo did not affect pacing-induced changes in ST-segment depression or RMLU. In conclusion, ANP attenuates ischemic ST-segment depression and lactate release during pacing-induced myocardial ischemia in patients with CAD. The antiischemic effect of ANP was not accompanied by any improvement in the regional myocardial oxygen supply/demand relationship. IMPLICATIONS: We evaluated the effects of i.v. atrial natriuretic peptide (50 ng x kg(-1) x min(-1)) on pacing-induced myocardial ischemia during general anesthesia in patients with coronary artery disease. In contrast to placebo, atrial natriuretic peptide attenuated ST-segment depression and myocardial lactate production and improved left ventricular function during pacing-induced ischemia. PMID- 9972742 TI - Drug therapy before coronary artery surgery: nitrates are independent predictors of mortality and beta-adrenergic blockers predict survival. AB - We conducted this study to evaluate whether there is an association between preoperative drug therapy and in-hospital mortality in patients undergoing coronary artery graft surgery. We collected data on 1593 consecutive patients undergoing coronary artery surgery. The relative risk of in-hospital mortality was determined by logistic regression with in-hospital mortality as the dependent variable, and independent variables that included known risk factors and preoperative cardioactive or antithrombotic drug treatment, i.e., age; left ventricular function; left main coronary artery disease; urgent priority; gender; previous cardiac surgery; concurrent cardiovascular surgery; chronic lung disease; creatinine concentration; hemoglobin concentration; diabetes; hypertension; cerebrovascular disease; recent myocardial infarction; prior vascular surgery; number of arteries bypassed; and regular daily treatment with beta-blockers, aspirin within 5 days, calcium antagonists, angiotensin converting enzyme (ACE) inhibitors, digoxin, or warfarin. In-hospital mortality was 3.3%. The relative risk of in-hospital mortality (with 95% confidence intervals of the relative risk) associated with the following drug treatments was: nitrates 3.8 (1.5-9.6), beta-blockers 0.4 (0.2-0.8), aspirin within 5 days 1.0 (0.5-1.9), calcium antagonists 1.1 (0.6-2.1), ACE inhibitors 0.8 (0.4-1.5), digoxin 0.7 (0.2 1.8), and warfarin 0.3 (0.1-1.6). We conclude that in-hospital mortality is positively associated with preoperative nitrate therapy and negatively associated with beta-adrenergic blocker therapy. A significant association between in hospital mortality and the preoperative use of calcium antagonists, ACE inhibitors, aspirin, digoxin, and warfarin was not confirmed. IMPLICATIONS: We examined the association between common drug treatments for ischemic heart disease and short-term survival after cardiac surgery using a statistical method to adjust for patients' preoperative medical condition. Death after surgery was more likely after nitrate therapy and less likely after beta-blocker therapy. PMID- 9972743 TI - Somatosensory evoked potential monitoring used to compare the effect of three asymmetric sternal retractors on brachial plexus function. AB - We compared the effect of three different asymmetric sternal retractors on brachial plexus dysfunction using intraoperative somatosensory evoked potentials (SSEPs). We studied 60 patients undergoing coronary bypass and internal mammary harvest. Assessment of brachial plexus function was performed pre- and postoperatively. Patients were assigned the use of a Pittman (MN Scientific Instruments Inc., Minneapolis, MN), Rultract (Rultract Inc., Cleveland, OH), or Delacroix-Chevalier (Delacroix-Chevalier, Paris, France) asymmetric sternal retractor for internal mammary exposure. SSEP changes from baseline during asymmetric retractor use and removal were determined, and average changes were compared among the retractor groups. Patient demographics and baseline SSEP values were similar. Fewer patients in the Delacroix-Chevalier group had decreases in SSEP amplitudes after retractor placement. Of the patients in the Rultract and Pittman groups, 45% and 25%, respectively, had amplitude decreases of >50%, compared with only 5% of the Delacroix-Chevalier patients. Three patients in both the Pittman and Rultract groups and one patient in the Delacroix Chevalier group suffered brachial plexus symptoms postoperatively. We conclude that the Delacroix-Chevalier retractor is associated with less neurophysiologic evidence of brachial plexus dysfunction during asymmetric sternal retraction compared with either the Pittman or Rultract sternal retractors. IMPLICATIONS: We used somatosensory evoked potentials to assess the effect of several different asymmetric sternal retractors on brachial plexus dysfunction and to determine which produced the least evidence of nerve damage during surgical exposure of the internal mammary artery. PMID- 9972744 TI - Anesthesia for endobronchial laser surgery: a modified technique. AB - We describe a technique for endobronchial surgery with the neodynium:yttium aluminum-garnet laser, in which an insufflation catheter with side holes placed into the contralateral mainstem bronchus is used for high-frequency positive pressure ventilation. Thirty-five patients (45 procedures) were treated during general anesthesia using a rigid bronchoscope in combination with a fiberoptic bronchoscope. Perioperatively, oxygen saturation (SaO2), mean arterial pressure, and heart rate were recorded. SaO2 during the recovery period was comparable to that during the intraoperative period but was significantly (P < 0.05) higher than that before the induction of anesthesia. There was a considerable (> or = 5%) increase in SaO2 at the end of the treatment in six patients, which indicates that the recanalization of the treated airway was successful. Our data support the assumption that, during endobronchial resection, selective ventilation of the nonaffected lung was adequate; in addition, subcarinal placement of the insufflation catheter with side holes was advantageous. We conclude that this technique contributes to the prevention of lung complications during endobronchial laser surgery. IMPLICATIONS: We describe a technique in which an insufflation catheter with side holes placed into the contralateral mainstem bronchus largely prevented inhalation of laser smoke and aspiration of blood and debris. PMID- 9972745 TI - Predicting the size of a double-lumen endobronchial tube using computed tomographic scan measurements of the left main bronchus diameter. AB - We investigated the use of chest computer tomographic (CT) scan measurement of the left mainstem bronchial diameter to predict the correct left-sided double lumen endobronchial tube (DLT) size in Asian patients who may require smaller DLT sizes. Fifty consecutive Asian adults aged 17-80 yr with preoperative chest CT scans undergoing elective thoracic surgery were entered into the study. The measurements of the left main bronchus diameter were made by using the electronic calipers of the spiral scanner to the nearest millimeter. The sizes of DLT selected were 32F, 35F, 37F, 39F, and 41F for left main bronchus diameters of <10 mm, 10 mm, 11 mm, 12 mm, and >12 mm, respectively. All DLT placements were confirmed and positioned by using fiberoptic bronchoscopy. The tracheas of all patients were successfully intubated with the predicted DLT sizes. Thirty-four patients (68%) were predicted to require smaller DLTs (37F or smaller). Six patients were correctly predicted to receive 32F DLTs. Twelve patients (24%) received an oversized DLT, but none received an undersized DLT. The overall positive predictive value for the male and female patients was 84.4% and 61.1%, respectively. Our study showed that CT scan measurements of the diameter of the left bronchus were especially useful in choosing smaller DLTs. IMPLICATIONS: We used computer tomographic scans to measure the diameter of the left mainstem bronchus, then selected the size of the left-sided double-lumen endobronchial tube (DLT) accordingly. We found that we could predict the sizes of the DLT fairly accurately, especially the smaller DLTs. PMID- 9972746 TI - Transnasal transesophageal echocardiography: a modified application mode for cardiac examination in ventilated patients. AB - In 42 endotracheally intubated patients, we examined the utility of a miniaturized monoplane probe for transnasal transesophageal echocardiography (TEE). Transnasal TEE was prospectively evaluated in 26 deeply and 16 mildly sedated patients receiving topical anesthesia with lidocaine jelly 2%. The patients with deep sedation were additionally examined with transoral monoplane and multiplane TEE. Transnasal esophageal insertion of the TEE probe was successfully performed in 90% of patients. Endotracheal malpositioning was corrected in two patients. Nasal bleeding required treatment in another patient. Topical anesthesia was adequate in 82% of mildly sedated patients. Left ventricular short- and four-chamber long-axis views of good quality were obtained with transnasal (transoral) monoplane TEE in 76% (81%) and 92% (96%) of patients (differences not significant). Compared with conventional multiplane TEE, transnasal monoplane TEE missed diagnoses in 19% of patients. The relative error (mean +/- SEM) of quantification with transnasal TEE was <9% +/- 2% for ventricular diameters and <7% +/- 2% for cross-sectional area measurements, with a bias of 0.5 +/- 3.8 cm2 and 0.1 +/- 2.4 cm2 (mean +/- 2 SD) for left ventricular end-diastolic and end-systolic short-axis areas. The relative error in measuring intracardiac flow velocities was >40%, but systolic to diastolic peak velocity ratios at the valvular site were determined with an error <4% +/- 3%. Transnasal monoplane TEE can be performed even in mildly sedated patients with an endotracheal tube without further need for analgesia or sedation. The technique is as useful as conventional transoral TEE to image standard tomographic planes for quantification, but it is less suited for comprehensive echocardiographic diagnosing. IMPLICATIONS: Transnasal insertion of a miniaturized monoplane transesophageal echocardiography (TEE) probe was studied in endotracheally intubated patients. Nasal passage was well tolerated even by patients with only mild sedation. Imaging quality was similar to conventional transoral monoplane TEE with larger transducers, but technical restraints cause a deficit in complete cardiac diagnosing obtained with multiplane TEE. PMID- 9972747 TI - Thromboelastography-guided transfusion algorithm reduces transfusions in complex cardiac surgery. AB - Transfusion therapy after cardiac surgery is empirically guided, partly due to a lack of specific point-of-care hemostasis monitors. In a randomized, blinded, prospective trial, we studied cardiac surgical patients at moderate to high risk of transfusion. Patients were randomly assigned to either a thromboelastography (TEG)-guided transfusion algorithm (n = 53) or routine transfusion therapy (n = 52) for intervention after cardiopulmonary bypass. Coagulation tests, TEG variables, mediastinal tube drainage, and transfusions were compared at multiple time points. There were no demographic or hemostatic test result differences between groups, and all patients were given prophylactic antifibrinolytic therapy. Intraoperative transfusion rates did not differ, but there were significantly fewer postoperative and total transfusions in the TEG group. The proportion of patients receiving fresh-frozen plasma (FFP) was 4 of 53 in the TEG group compared with 16 of 52 in the control group (P < 0.002). Patients receiving platelets were 7 of 53 in the TEG group compared with 15 of 52 in the control group (P < 0.05). Patients in the TEG group also received less volume of FFP (36 +/- 142 vs 217 +/- 463 mL; P < 0.04). Mediastinal tube drainage was not statistically different 6, 12, or 24 h postoperatively. Point-of-care coagulation monitoring using TEG resulted in fewer transfusions in the postoperative period. We conclude that the reduction in transfusions may have been due to improved hemostasis in these patients who had earlier and specific identification of the hemostasis abnormality and thus received more appropriate intraoperative transfusion therapy. These data support the use of TEG in an algorithm to guide transfusion therapy in complex cardiac surgery. IMPLICATIONS: Transfusion of allogeneic blood products is common during complex cardiac surgical procedures. In a prospective, randomized trial, we compared a transfusion algorithm using point-of-care coagulation testing with routine laboratory testing, and found the algorithm to be effective in reducing transfusion requirements. PMID- 9972749 TI - Plasma concentration of adrenomedullin is increased in hemorrhagic shock in dogs. PMID- 9972748 TI - Organization of the sympathetic innervation of the forelimb resistance vessels in the cat. AB - Detailed information on the outflow pathway of sympathetic vasoconstrictor fibers to the upper extremity is lacking. We studied the organization of the sympathetic innervation of the forelimb resistance vessels and of the sinoatrial (SA) node in the decerebrated, artificially respirated cat. The distal portion of sectioned individual rami T1-8 and the sympathetic chain immediately caudal to T8 on the right side were electrically stimulated while the right forelimb perfusion pressure (forelimb perfused at constant flow) and heart rate were recorded. Increases in perfusion pressure were evoked by stimulation of T2-8 (maximal response T7: 55 +/- 2.3 mm Hg). Responses were still evoked by stimulation of the sympathetic chain immediately caudal to T8 (44 +/- 15 mm Hg). Increases in heart rate were evoked by the stimulation of more rostral rami (T1-5; maximal response T3: 55.2 +/- 8 bpm). These vasoconstrictor and cardioacceleratory responses were blocked by the cholinergic antagonists hexamethonium and scopolamine. Sectioning of the vertebral nerve and the T1 ramus abolished the vasoconstrictor response. Stimulation of the vertebral nerve and of the proximal portion of the sectioned T1 ramus increased perfusion pressure (69 +/- 9 and 34 +/- 14 mm Hg, respectively), which was unaffected by ganglionic cholinergic block. These data suggest that forelimb resistance vessel control is subserved by sympathetic preganglionic neurons located mainly in the middle to caudal thoracic spinal segments. Some of the postganglionic axons subserving vasomotor function course through the T1 ramus, in addition to the vertebral nerve. IMPLICATIONS: Forelimb vasculature is controlled by sympathetic preganglionic neurons located in middle to caudal thoracic spinal segments and by postganglionic axons carried in the T1 ramus and vertebral nerve. This helps to provide the anatomical substrate of interruption of sympathetic outflow to the upper extremity produced by major conduction anesthesia of the stellate ganglion or spinal cord. PMID- 9972750 TI - Intracranial pressure and venous cannulation for cardiopulmonary bypass. PMID- 9972751 TI - Acute myocardial infarction during lung volume reduction surgery. PMID- 9972752 TI - Craniotomy procedures are associated with less analgesic requirements than other surgical procedures. AB - The conventional wisdom that neurosurgical patients experience minimal postoperative pain and require little analgesia has been challenged. To address this, we reviewed our anesthesia and postanesthesia care unit (PACU) records for 1995 and compared pain management in patients undergoing major intracranial and selected extracranial procedures. We recorded patient weight, operative time, time in the PACU, intraoperative and postoperative opioid use, PACU pain scores, and level of consciousness in patients who had undergone open fixation of mandible or maxilla (Group E), clipping of aneurysms or excision of tumors (Group I), or lumbar laminectomy (Group L). Group I (n = 78) patients received less fentanyl in the operating room (0.016 microg x kg(-1) x min(-1) versus 0.023 microg x kg(-1) x min(-1) for Group E [n = 134] and 0.023 microg x kg(-1) x min( 1) for Group L [n = 21]; P < 0.05), received less morphine in the PACU (0.0004 vs 0.0013 vs 0.0015 mg kg(-1) x min(-1); P < 0.005), reported lower pain scores (0.76 vs 2.5 vs 2.4; P < 0.05), and spent less time in the PACU (89.5 vs 109 vs 105 min; P < 0.05) than Group E or L patients. Our results were similar when only patients with Glasgow Coma Scale scores > or = 14 were used in a subset analysis. We conclude that patients suffer less pain and use fewer opioids in the PACU after intracranial surgery than after facial reconstruction or lumbar laminectomy. Our results confirm that the average craniotomy patient has less postoperative pain than patients who undergo other surgical procedures, although patients who undergo frontal craniotomy may require more aggressive pain management. IMPLICATIONS: This study compares the pain report and analgesic use in patients after intracranial versus extracranial surgery. The results confirm the commonly held but recently challenged belief that neurosurgery patients suffer less pain postoperatively than other patients. In this study, we found that most patients report minimal pain after intracranial surgery but that a small subset of patients, many of whom have undergone frontal craniotomies, require aggressive treatment of postoperative pain. PMID- 9972753 TI - Dynamic cerebral autoregulation during sevoflurane anesthesia: a comparison with isoflurane. AB - We investigated dynamic cerebral pressure autoregulation awake and during 1.5 minimum alveolar anesthetic concentration (MAC) sevoflurane or isoflurane anesthesia in 16 patients undergoing nonintracranial neurosurgical procedures. All patients received a standardized anesthetic, and their lungs were ventilated with 1.5 MAC volatile anesthetic in 100% oxygen to normocapnia. Routine monitors included electrocardiogram, pulse oximetry, end-tidal capnography, and continuous noninvasive blood pressure. In addition, middle cerebral artery blood velocity (Vmca) was measured continuously using transcranial Doppler ultrasonography. Dynamic cerebral autoregulation was tested by inducing a rapid transient decrease in mean arterial pressure by deflation of large thigh cuffs, which were placed around both thighs and inflated to 100 mm Hg above systolic pressure. The Vmca response to the decrease in blood pressure was fitted to a series of curves to determine the rate of dynamic cerebral autoregulation (dRoR). Awake dRoR values were similar in the isoflurane and sevoflurane groups, 32 +/- 2%/s and 29 +/- 2%/s, respectively. dRoR decreased to 5 +/- 1%/s during isoflurane anesthesia but to only 24 +/- 2%/s during sevoflurane anesthesia. We conclude that dynamic cerebral autoregulation is better preserved during sevoflurane than isoflurane anesthesia in humans. IMPLICATIONS: We investigated the effect of sevoflurane and isoflurane on dynamic cerebral pressure autoregulation using transcranial Doppler ultrasonography. At 1.5 minimum alveolar anesthetic concentration, dynamic autoregulation was better preserved during sevoflurane than isoflurane anesthesia. PMID- 9972754 TI - Determination of an effective dose of intrathecal morphine for pain relief after cesarean delivery. AB - Very small doses of intrathecal (i.t.) morphine (25-200 microg) have been used in an effort to provide effective postoperative pain relief while minimizing side effects after cesarean delivery. We performed a double-blinded study in 40 patients presenting for elective cesarean delivery in which i.t. morphine was administered along with oral hydrocodone/acetaminophen and other medications commonly administered after cesarean delivery. We administered i.t. morphine by up-down sequential allocation of doses. For the purposes of this study, adequate postoperative analgesia was defined as comfort not requiring i.v. morphine for 12 h after spinal anesthesia with bupivacaine, fentanyl, and morphine. In addition, a time and cost comparison was performed for study patients receiving intrathecal morphine compared with a historical group of patients receiving patient controlled analgesia with i.v. morphine. We were unable to determine with meaningful precision a dose of i.t. morphine to provide analgesia in this context. However, very small doses of i.t. morphine combined with oral hydrocodone/acetaminophen and other medications commonly prescribed after cesarean delivery provided postoperative pain relief with no more time commitment than patient-controlled analgesia (148 +/- 61 vs 150 +/- 57 min) and with significantly less acquisition cost ($15.13 +/- $4.40 vs $34.64 +/- $15.55). IMPLICATIONS: When used along with oral analgesics, very small doses of spinal morphine provide adequate pain relief after cesarean delivery. Spinal anesthetics, oral analgesics, and other medications commonly prescribed to treat side effects after cesarean delivery contribute significantly to this analgesia. When small doses of spinal morphine are used in this setting, they provide adequate analgesia and patient satisfaction that is time- and cost-effective. PMID- 9972755 TI - The effects of needle bevel orientation during epidural catheter insertion in laboring parturients. AB - Lateral needle bevel orientation during identification of the epidural space has been recommended to reduce the risk of postdural puncture headache (PDPH). Rotation to cephalad or caudad orientation before catheter insertion is assumed necessary for analgesic success. We prospectively compared the effects of catheter insertion through lateral- and cephalad-oriented Tuohy needle bevels in laboring parturients. Anesthesiology residents were randomized to identify the epidural space with bevels oriented cephalad or lateral. Catheters were inserted without needle rotation. Outcomes compared included ease of insertion, analgesic effectiveness, and complications. We evaluated 534 catheter insertions in 500 parturients. Initial catheter insertion produced satisfactory analgesia in 80.2% of the lateral group versus 91.1% of the cephalad group (P < 0.001). Resistance preventing catheter insertion accounted for the difference. There were no differences in i.v. cannulation (5.8% vs 5.1%), dural puncture (3.8% vs 2.0%), PDPH (0.4% vs 0.7%), or asymmetric block (31% vs 27%). There was a slightly higher rate of paresthesias in the lateral group (31% vs 23%; P = 0.048). In 78% of parturients experiencing both paresthesias and asymmetric block, the side of the paresthesia and greater extent of block were the same. Analgesic effectiveness, as measured by using a visual analog scale, was not different between the groups. IMPLICATIONS: Two methods of epidural catheter insertion were compared in laboring parturients. Catheter insertion with the needle orifice oriented cephalad was associated with the greatest initial success and the fewest complications. PMID- 9972756 TI - Changes in maternal middle cerebral artery blood flow velocity associated with general anesthesia in severe preeclampsia. AB - In women with severe preeclampsia, significant increases in mean arterial pressures (MAP) are common after rapid induction of general anesthesia (GA) and tracheal intubation. The objectives of this prospective study were to assess the effects of the rapid induction-intubation technique on middle cerebral artery (MCA) flow velocity in severe preeclampsia and to examine the correlation between mean MCA flow velocity (Vm) and MAP. Eight women with severe preeclampsia (study group) and six normotensive women at term (control group) scheduled to undergo cesarean section under GA were studied. Before induction, patients in the study group received i.v. labetalol in divided doses to lower diastolic pressures to <100 mm Hg. Anesthesia was induced with pentothal 4-5 mg/kg, followed by succinylcholine 1.5 mg/kg to facilitate tracheal intubation. A transcranial Doppler was used to measure Vm. Both Vm and MAP were recorded before induction and every minute for 6 min after intubation. In the study group, after the administration of labetalol, MAP decreased from 129 +/- 9 to 113 +/- 9 mm Hg (P < 0.05), and Vm decreased from 59 +/- 11 to 54 +/- 10 cm/s (P < 0.05). After intubation, MAP increased from 113 +/- 9 to 134 +/- 5 mm Hg (P < 0.001), and Vm increased from 54 +/- 10 to 70 +/- 10 cm/s (P < 0.001). In the control group, while MAP increased significantly from 89 +/- 6 to 96 +/- 4 mm Hg (P < 0.05) after intubation, the concurrent increase in Vm from 49 +/- 5 to 54 +/- 7 cm/s was not significant. There was a significant positive pooled correlation between Vm and MAP (r = 0.5, P < 0.0006) in the study group but not in the control group (r = 0.24). After induction and intubation, both Vm and MAP values were significantly increased in the study group patients at all observation points compared with the control group patients. The findings indicate that Vm increases significantly after rapid-sequence induction of GA and tracheal intubation in women with severe preeclampsia, and there seems to be a direct relationship between MAP and Vm. IMPLICATIONS: In women with severe preeclampsia, rapid sequence induction of general anesthesia and tracheal intubation can cause severe hypertension. Our results indicate that the increase in blood pressure is associated with a significant increase in maternal cerebral blood flow velocity and that there is a significant correlation between these two variables. PMID- 9972757 TI - Combination of intrathecal sufentanil 10 mug plus bupivacaine 2.5 mg for labor analgesia: is half the dose enough? AB - This controlled, double-blinded, prospective trial of 42 parturients in early labor was conducted to determine whether halving the total amount of intrathecal (i.t.) sufentanil and bupivacaine reduced the incidence of systemic hypotension while providing adequate analgesia with minimal lower limb motor block. Combined spinal-epidural analgesia (CSE) was instituted; Group A (n = 21) received a total of 10 microg of sulfentanil plus 2.5 mg of bupivacaine, whereas Group B (n = 21) received half that dose. Compared with Group B, Group A had a higher incidence of hypotension (nine parturients in Group A, two in Group B; P < 0.05), a greater degree of motor block (P < 0.05), and a higher incidence of sedation (nine parturients in Group A were sedated, one in Group B; P < 0.01). Group B had higher pain scores for the first 5 min (P < 0.05) and a lower level of sensory blockade (median of T7 in Group B compared with T4 in Group A; P < 0.01). We conclude that halving the total amount of i.t. 10 microg of sufentanil plus 2.5 mg of bupivacaine is a suitable option for CSE in labor because it reduces the incidence of some side effects, such as hypotension and maternal sedation, without compromising overall high maternal satisfaction. IMPLICATIONS: We showed that adequate labor pain relief could be provided by halving the recommended dose of 10 microg of intrathecal sufentanil plus 2.5 mg of bupivacaine. The larger dose, however, produced faster pain relief, which lasted longer than the reduced dose. The mother and baby were not adversely affected with either dose. PMID- 9972758 TI - Epidural steroids for treating "failed back surgery syndrome": is fluoroscopy really necessary? AB - Epidural steroids are commonly administered in the treatment of "failed back surgery syndrome." Because patient response is dependent on accurate steroid placement, fluoroscopic guidance has been advocated. However, because of ever increasing medical expenditures, the cost-benefit of routine fluoroscopy should be critically evaluated. Therefore, 50 patients were enrolled into this institutional review board-approved, prospective, controlled, single-blinded study. At a predetermined intervertebral level, the epidural space was identified using an air loss of resistance technique. Thereafter, an epidural catheter was inserted 2 cm through the epidural needle. To determine the accuracy of the clinical placement, contrast medium was administered through the epidural catheter; antero-posterior and lateral lumbar spine radiographs were then obtained. The number of attempts required to successfully locate the epidural space, the reliability of the air loss of resistance technique in indicating successful epidural penetration in failed back surgery syndrome, the ability of the clinician to accurately predict the intervertebral space at which the epidural injection was performed, and the spread of contrast medium within the epidural space were recorded. A total of 48 epidurograms were performed. The number of attempts to successfully enter the epidural space was 2 +/- 1. In 44 cases, the radiological studies confirmed the clinical impression that the epidural space had been successfully identified. In three patients, the epidural catheter was in the paravertebral tissue. One myelogram was recorded. In 25 patients, the epidural catheter did not pass through the predetermined intervertebral space. In 35 cases, the contrast medium did not reach the level of pathology. IMPLICATIONS: The clinical sign of loss of resistance is a reliable indicator of epidural space penetration in most cases of "failed back surgery syndrome." However, surface anatomy is unreliable and may result in inaccurate steroid placement. Finally, despite accurate placement, the depot-steroid solution will spread to reach the level of pathology in only 26% of cases. PMID- 9972759 TI - Temperature monitoring practices during regional anesthesia. AB - Monitoring and maintaining body temperature during the perioperative period has a significant impact on the risk of myocardial ischemia, cardiac morbidity, wound infection, surgical bleeding, and patient discomfort. To test the hypothesis that body temperature is inadequately monitored during regional anesthesia (RA), we randomly surveyed 60 practicing anesthesiologists to determine practice patterns for temperature monitoring. Only 33% of the clinicians surveyed routinely monitor body temperature during RA. Although skin temperature monitoring has limitations, it was the most commonly used method among the survey respondents. When temperature is monitored during RA, most clinicians use either liquid crystal skin-surface monitoring or axillary temperature probes. Of those surveyed, < 15% use acceptable core temperature monitoring techniques (urinary bladder or tympanic membrane). In conclusion, it seems that body temperature is often not monitored in patients receiving RA. IMPLICATIONS: The results of this survey of practicing anesthesiologists indicate that body temperature is often not monitored in patients receiving regional anesthesia. It is therefore likely that significant hypothermia goes undetected and untreated in these patients. PMID- 9972760 TI - Beta-adrenergic blockers and vasovagal episodes during shoulder surgery in the sitting position under interscalene block. AB - Shoulder surgery is often performed with patients in the sitting position under interscalene block anesthesia. Vasovagal episodes, characterized by a sudden decrease in heart rate and/or blood pressure, have a reported incidence of 17% 24% in this setting. We performed a retrospective study to determine whether there was an association between the use of beta-adrenergic blockers and the incidence of these episodes. Of the 150 patients identified, 20 (13.3%) had a vasovagal event. Similar proportions of patients had received a beta-adrenergic blocker in the group who had a vasovagal event compared with those who did not (20% vs 18%; P = 0.95). No other differences could be identified. We conclude that vasovagal episodes occur frequently in this setting with no identifiable risk factors. Beta-adrenergic blockers were not associated retrospectively with either an increased or decreased incidence of these episodes. The most likely mechanism involves the Bezold-Jarisch reflex. IMPLICATIONS: In this retrospective study of 150 patients who underwent shoulder surgery in the sitting position under interscalene block, we found a 13% incidence of vasovagal episodes. Unlike a previous study, this was not affected by the use of beta-blockers. A randomized, prospective study is necessary to clarify this issue. PMID- 9972761 TI - The risk of persistent paresthesia is not increased with repeated axillary block. AB - Neurologic deficits are noted on physical examination in approximately 0.2%-19% of patients after regional anesthetic techniques. Laboratory and clinical studies suggest that a subclinical neuropathy occurs much more often. Performing a regional anesthetic technique during this period may result in additional nerve trauma. We evaluated the frequency of neurologic complications in patients undergoing repeated axillary block. A total of 1614 blocks were performed on 607 patients. The median number of blocks per patient was two (range 2-10 blocks). The median interval between blocks was 12.6 wk, including 188 (31%) patients who received multiple blocks within 1 wk. Sixty-two neurologic complications occurred in 51 patients for an overall frequency of 8.4%. Of the 62 nerve injuries, 7 (11.3%) were related to the anesthetic technique; the remaining 55 (88.7%) were a result of the surgical procedure. Patient age and gender, the presence of preexisting neurologic conditions, a surgical procedure to a nerve, and total number of blocks did not increase the risk of neurologic complications. No regional anesthetic technique risk factors, including elicitation of a paresthesia, selection of local anesthetic, or addition of epinephrine, were identified. The success rate was higher with the paresthesia technique than with nerve stimulator technique or transarterial injection, and with use of mepivacaine versus bupivacaine. We conclude that the frequency of neurologic complications in patients undergoing repeated axillary block is similar to that in patients receiving a single regional technique. These patients are not likely to be at increased risk of neurologic complications. IMPLICATIONS: The risk of neurologic complications was not increased in patients who underwent multiple axillary blocks, even within a 1-wk interval. No risk factors for anesthetic related complications were identified. However, block success rate was increased with the paresthesia technique and the injection of mepivacaine versus bupivacaine. PMID- 9972762 TI - Neurologic complications after placement of cerebrospinal fluid drainage catheters and needles in anesthetized patients: implications for regional anesthesia. Mayo Perioperative Outcomes Group. AB - Subarachnoid or epidural needle placement in an anesthetized patient is controversial because general anesthesia and muscle relaxation may mask neural trauma. However, placement of a needle or catheter in the subarachnoid space for the purpose of cerebral spinal fluid (CSF) drainage is frequently performed in anesthetized patients undergoing neurosurgery. The records from 530 consecutive transsphenoidal surgeries performed with lumbar CSF drainage were reviewed to determine the types of neurologic complications attributable to spinal drainage and their rates of occurrence. All patients were anesthetized during CSF drain placement. A 19-gauge malleable needle was placed in 473 (89%) patients. Subarachnoid catheters (20- or 16-gauge catheters placed via 18- or 14-gauge epidural needles, respectively) were placed in 17 (3%) patients. In 40 (8%) patients, the type of drain was unspecified. No new neurologic deficits attributable to spinal drain insertion were detected in the immediate postoperative period or within 1 yr of surgery. Thirteen patients developed postdural puncture headache (2.5%, exact 95% confidence interval 1.3%-4.2%); seven required epidural blood patch (1.3%, 0.5%-2.7%). The low incidence (0%, 0.0%-0.7%) of neurologic injury from spinal drain insertion in anesthetized patients from this study is similar to the incidence of neurologic complications historically reported for both CSF drain insertion and spinal anesthesia. IMPLICATIONS: The performance of regional anesthesia in an anesthetized patient is controversial due to the possibility of unrecognized nerve injury. We report no cases of nerve injury caused by the placement of cerebrospinal fluid drainage needles and catheters in 530 anesthetized patients undergoing neurosurgery. PMID- 9972763 TI - No risk of metal toxicity in combined spinal-epidural anesthesia. AB - Using the single level needle-through-needle technique for combined spinal epidural anesthesia (CSE) may introduce very fine metal particles abraded by the spinal needle from the inner ground edge of the Tuohy needle into the patient. Either the local anesthetic administered epidurally or the peridural catheter may also pass intrathecally through the hole in the dura made by the spinal needle. To examine these concerns, the needle-through-needle technique was simulated in an in vitro model (18-gauge Tuohy needle; 27- or 29-gauge Quincke needle). The presence of abraded metal particles was identified by atomic absorption spectrography (AAS). The needles were then examined under an electron microscope. Metal particles could not be identified by using AAS in the needle-through-needle technique after normal clinical use, nor could traces of use be revealed by using an electron microscope to examine the Tuohy needle. With intentionally rough handling and caudal orientation of the spinal needle tip, minimal scratches could be seen by using an electron microscope, but there were no metal particles detected by AAS. In an anatomical preparation, the possible passage of the epidural catheter anesthetic through the dural puncture hole into the cerebrospinal fluid compartment was investigated endoscopically. Neither passage of dyed epidural local anesthetic nor penetration of the epidural catheter into the cerebrospinal fluid compartment could be demonstrated by endoscopy. We conclude that the needle-through-needle-technique is an acceptable way of performing CSE anesthesia. Endangering the patient by an unintentionally intrathecal misplacement of the epidural catheter seems to be very unlikely based on our in vitro model if small spinal needles (27- or 29-gauge) are used. IMPLICATIONS: Atomic absorption spectrography shows no contamination of the intrathecal compartment by abraded metal particles from the Tuohy needle by combined spinal-epidural anesthesia with the needle-through-needle technique. In vitro, neither passage of dyed epidural local anesthetic nor penetration of the epidural catheter into the cerebrospinal fluid compartment could be demonstrated by endoscopy. PMID- 9972764 TI - Assessment of the level of sensory block after subarachnoid anesthesia using a pressure palpator. AB - In a cross-over study, we compared two methods of assessing the level of sensory block during subarachnoid anesthesia: the traditional pinprick sensation or a novel pressure palpator exerting a pressure of 650 g. Fifty patients scheduled for transurethral surgery under subarachnoid anesthesia were randomly assigned to be tested for spread of sensory block. In Group 1, the pressure palpator was followed by pinprick; in Group 2, the reverse sequence was used. Evaluation was performed 15 and 25 min after the subarachnoid injection of 2 mL of 5% lidocaine hyperbaric solution. In Group 1, the level of sensory block assessed with the pressure palpator was 1.7 +/- 3.2 cm (0.5 +/- 1.2 dermatomes) higher than that with the pinprick at 15 min, and 2.2 +/- 3.4 cm (0.6 +/- 1.0 dermatomes) higher than that with the pinprick 25 min after the block. In Group 2, the difference was accentuated. The level of sensory block assessed by pinprick 15 min after subarachnoid lidocaine was 5.7 +/- 4.8 cm (1.2 +/- 0.9 dermatomes) lower than the level with the pressure palpator, and 4.2 +/- 3.3 cm (0.9 +/- 0.6 dermatomes) lower than that with the pressure palpator at 25 min. In all instances, the pressure palpator gave a significantly higher assessment than the pinprick. We conclude that the pressure palpator, when preceded by the pinprick test, is associated with an increased threshold. This method may be useful in assessing the sensory block produced by subarachnoid anesthesia. IMPLICATIONS: A novel pressure palpator that maintains the integrity of the epidermis was used to assess the level of sensory block after subarachnoid anesthesia and was compared with the standard method of the pinprick sensation. This method assessed the block consistently higher than the pinprick method, but it may have advantages as a noninvasive sensory test. PMID- 9972765 TI - The effects of thoracic epidural anesthesia on intraoperative visceral perfusion and metabolism. AB - After institutional approval and informed consent, we studied the effect of epidural bupivacaine 0.5% on visceral perfusion and metabolism by using gastric mucosal tonometry in 30 patients in a placebo-controlled fashion. The maximal intramucosal pH (pHi) decrease was significantly (P < 0.001) greater in the control group (0.16 +/- 0.04) than in the thoracic epidural anesthesia (TEA) group (0.07 +/- 0.05). There were 10 patients in the control group and 2 patients in the TEA group who had evidence of gastric mucosal ischemia (pHi <7.32) at the end of the study (P< 0.01). The differences in pHi and intramucosal CO2 (PiCO2) became statistically significant between the groups after 180 and 240 min. The study data show that TEA prevents the decrease of pHi during major abdominal surgery, perhaps as an effect of stable visceral perfusion. We conclude that TEA may be a valuable method for intra- and postoperative treatment of surgical stress. IMPLICATIONS: The present study shows that thoracic epidural anesthesia prevents a decrease of intramucosal pH during major abdominal surgery, which suggests that thoracic epidural anesthesia may be a valuable tool for the treatment of surgical stress. PMID- 9972766 TI - An examination of the interactions between the antinociceptive effects of morphine and various mu-opioids: the role of intrinsic efficacy and stimulus intensity. AB - We examined the effects of several opioids that vary in intrinsic efficacy at the mu-opioid receptor alone and in combination with morphine in a rat warm water tail withdrawal procedure using 50 degrees C and 52 degrees C water (i.e., low- and high-stimulus intensities). Morphine, levorphanol, dezocine, and buprenorphine produced dose-dependent increases in antinociception using both stimulus intensities. Butorphanol produced maximal levels of antinociception at the low, but not at the high, stimulus intensity, whereas nalbuphine failed to produce antinociception at either stimulus intensity. For cases in which butorphanol and nalbuphine failed to produce antinociception alone, these opioids dose-dependently antagonized the effects of morphine. When levorphanol, dezocine, and buprenorphine were combined with morphine, there was a dose-dependent enhancement of morphine's effects. Similar effects were obtained at the low stimulus intensity when butorphanol was administered with morphine. In most cases, the effects of these combinations could be predicted by summating the effects of the drugs when administered alone. These results indicate that the level of antinociception produced by an opioid is dependent on the intrinsic efficacy of the drug and the stimulus intensity. Furthermore, the level of antinociception produced by the opioid, not necessarily the opioids' intrinsic efficacy, determines the type of interaction among opioids. IMPLICATIONS: Compared with high-efficacy opioids, lower efficacy opioids produce lower levels of pain relief, especially in situations of moderate to severe pain. When opioids are given in combination, the effects can only be predicted on the basis of the antinociception obtained when the drugs are administered alone. PMID- 9972767 TI - Pre- versus postinjury effects of intravenous GABAergic anesthetics on formalin induced Fos immunoreactivity in the rat spinal cord. AB - We evaluated the suppression of spinal Fos-like immunoreactivity (FLI) by i.v. anesthetics in the rat formalin model. Preformalin injection (1.5% subcutaneously) treatment groups included i.v. saline controls and three i.v. GABAergic anesthetic groups (pentobarbital 20 mg/kg, propofol 10 mg/kg, or alphaxalone 1.5 mg/kg; n = 12 per group). After perfusion 2 h postformalin, spinal cords were dissected, sliced at 30 microm, and processed by immunoperoxidase staining with an antibody against the Fos protein. Quantification and determination of the laminar distribution of Fos-labeled nuclei were performed at the L4-5 spinal level ipsilateral to formalin injection. Drug groups demonstrating FLI suppression were comparatively studied in a 5-min postformalin treatment group. Pentobarbital pretreatment failed to suppress FLI. However, significant reductions (percent decrease) of FLI were observed with propofol (63%) and alphaxalone (30%) compared with saline controls. Pre- versus postformalin comparison studies showed that propofol, but not alphaxalone, suppressed FLI more effectively when given preformalin. Given the observed inconsistencies between this study of Fos expression and our previous behavioral study, it is questionable whether anesthetic modulation of noxious stimulus induced FLI parallels that of behavioral responses. IMPLICATIONS: In this study, we examined whether i.v. general anesthetics (propofol, alphaxalone, and pentobarbital) prevent injury-induced spinal cord changes. We measured spinal Fos protein after rats received anesthetics before versus after a formalin injection. Fos inhibition patterns were inconsistent with behavioral studies of these anesthetics, suggesting that Fos inhibition does not always correlate with behavioral analgesia. PMID- 9972768 TI - Anesthesia for intranasal surgery: a comparison between tracheal intubation and the flexible reinforced laryngeal mask airway. AB - The purpose of the study was to assess the suitability and safety of the flexible reinforced laryngeal mask airway (FRLMA) for intranasal surgery (INS) anesthesia. A secondary objective was to compare the incidence of complications of removal of the FRLMA with tracheal extubation in awake and anesthetized patients. One hundred fourteen ASA physical status I and II patients requiring INS were randomly assigned into three groups: Group I = FRLMA, Group II = endotracheal tube (ET) extubated awake, and Group II = ET extubated deeply anesthetized. In Group I, the incidence of coughing and oxyhemoglobin desaturation at removal was significantly reduced compared with that in Groups II and III (P < 0.05). There were no episodes of postremoval laryngospasm in Group I; in Group III, the incidence was 19% (P < 0.05), whereas in Group II, it was 6% (not significantly different). The number of patients with oxyhemoglobin desaturation < or = 92% on admission to the postanesthesia care unit was 0% in Group I, 26% in Group II (P < 0.05), and 16% in Group III (not significantly different). At bronchoscopy, the incidence of blood visible in the airway was low and similar among the three groups (3%, 6%, and 3%, respectively). There were no significant differences in the incidence of airway complications between Groups II and III. IMPLICATIONS: We compared airway management for intranasal surgery anesthesia using a new device, the flexible reinforced laryngeal mask airway, with the current standard of tracheal intubation. The study demonstrates that the flexible reinforced laryngeal mask airway can provide a safe, protected airway with a smoother emergence from anesthesia than tracheal intubation. PMID- 9972769 TI - Assessing neuromuscular block at the larynx: the effect of change in resting cuff pressure and a comparison with video imaging in anesthetized humans. AB - Neuromuscular block (NMB) at the larynx has been assessed by measuring the cuff pressure (CP) in an endotracheal tube (ETT) placed between the vocal cords. In this study, we evaluated the decrease in resting cuff pressure (RCP) after the administration of rocuronium and the effect of this decrease on the assessment of NMB, and we compared CP measurement with an alternative technique, video imaging (VI). In 20 patients, NMB was determined at the hand by mechanomyography and at the larynx initially by CP and subsequently by VI, recording images using a fiberoptic bronchoscope via a laryngeal mask. Train-of-four stimuli were applied at both sites. After baseline measurements, the ETT was replaced, and rocuronium was infused to achieve a steady-state 50% (n = 10) or 75% (n = 10) block at the hand. CP measurements were recorded before and after restoration of RCP to prerocuronium pressure, followed by further VI measurements. The mean RCP decreased from 21 +/- 4 to 12 +/- 5 mm Hg after rocuronium. At 50% block at the hand, the CP estimate of block at the larynx with reduced RCP was 62% +/- 18%, and that after restoring RCP was 29% +/- 13%; VI estimated 27% +/- 14% block. At 75% block at the hand, CP and VI estimated 52% +/- 11% and 46% +/- 9% block, respectively (RCP maintained). We conclude that RCP decreases after the administration of rocuronium, that restoring RCP significantly alters CP estimates of NMB, and that VI is in agreement with CP measurement if RCP is maintained at prerelaxant values. IMPLICATIONS: In this study, we show that a muscle relaxant-induced decrease in resting tension at the larynx may confound the assessment of neuromuscular block by cuff pressure measurement. The preliminary data suggest that video imaging may provide a suitable alternative to cuff pressure measurement to assess neuromuscular block at the larynx. PMID- 9972771 TI - Dose of compound A, not sevoflurane, determines changes in the biochemical markers of renal injury in healthy volunteers. AB - Administration of sevoflurane in a circle absorption system generates Compound A, a nephrotoxin in rats. Reports examining the potential of Compound A to produce renal injury in humans have provided conflicting results. We tested the possibility that there is a threshold to Compound A-induced renal injury in humans and that, above this threshold, renal injury increases with increasing doses of Compound A. Eleven volunteers received 3% sevoflurane for 8 h at 2 L/min, and three volunteers received 3% sevoflurane for 8 h at 4-6 L/min. We measured inspired and expired concentrations of Compound A and urinary excretion of albumin, alpha-glutathione-S-transferase (GST), and glucose. The median urinary excretion of albumin, glucose, and alpha-GST for the first 3 days after anesthesia increased significantly from preanesthetic values in the 2-L/min group. Compound A doses < 240 ppm-h resulted in normal urinary excretion of albumin, glucose, and alpha-GST. Five of seven subjects who received doses > 240 ppm-h had abnormal excretion of albumin, and six of seven had abnormal alpha-GST urinary excretion (P < 0.05). Urinary excretion of albumin, alpha-GST, and glucose was normal by 14 days after exposure. We conclude that sevoflurane administration for 8 h at 2 L/min results in albuminuria and enzymuria when the dose of Compound A exceeds 240 ppm-h. That is, a Compound A concentration of 30 ppm breathed for > or = 8 h may produce transient renal injury. IMPLICATIONS: We examined the dose-response relationship of sevoflurane/Compound A and urinary excretion of albumin, glucose, and alpha-GST. Sevoflurane exposure for 8 h at a 2 L/min inflow rate produces transient albuminuria and enzymuria in healthy volunteers when the dose of Compound A exceeds 240 ppm-h (30 ppm for 8 h). PMID- 9972770 TI - The in vitro effects of isoflurane, sevoflurane, and propofol on platelet aggregation. AB - We studied the in vitro effects of sevoflurane, isoflurane, and propofol anesthesia on platelet function. Thirty patients undergoing minor surgical procedures were divided into three groups (n = 10 each). Induction of anesthesia was achieved by using 5 mg/kg thiopental i.v., and 0.1 mg/kg vecuronium i.v. was used for muscle relaxation. Anesthesia maintenance was provided by sevoflurane in the first, isoflurane in the second, and propofol infusion in the third group with 70% N2O in O2. Hemoglobin, hematocrit, thrombocyte count, prothrombin time, activated partial thromboplastin time, international normalized ratio, arterial pH, von Willebrand factor, viscosity, platelet aggregation, and bleeding time were measured 1 h pre-, intra-, and postanesthesia. There was no difference among the platelet aggregation ratios of the pre-, intra-, and postoperative periods in the isoflurane group. The aggregation ratios in the sevoflurane and propofol groups were significantly reduced at intraoperative periods compared with preoperative values. Diminished aggregation values were also found 1 h postoperatively compared with the control values in the sevoflurane and propofol groups. We conclude that, in patients with a bleeding tendency during the intra- and early postoperative period, isoflurane may be preferred as a general anesthetic. IMPLICATIONS: In our study, using vacuum-operated tubes, we demonstrated that sevoflurane and propofol had a significant inhibitory effect on intraoperative and early postoperative platelet aggregation, whereas isoflurane had no effect. Therefore, isoflurane may be preferred as a general anesthetic in patients with a clinically relevant bleeding tendency. PMID- 9972772 TI - The effects of prostaglandin E1 on intraoperative temperature changes and the incidence of postoperative shivering during deliberate mild hypothermia for neurosurgical procedures. AB - We investigated the effects of i.v. prostaglandin E1 (PGE1) on intraoperative changes of core temperature and the incidence of postoperative shivering in neurosurgical patients undergoing deliberate mild hypothermia. Eighty-three patients were randomly assigned to one of three groups: patients in the control group did not receive PGE1, whereas patients in the PG20 group and PG50 group received PGE1 at a dose of 0.02 and 0.05 microg x kg(-1) x min(-1), respectively. The administration of PGE1 was started just after the induction of anesthesia and continued until the end of anesthesia. Anesthesia was maintained with nitrous oxide in oxygen, sevoflurane, and fentanyl. After the induction of anesthesia, patients were cooled using a water blanket and a convective device blanket. Tympanic membrane temperature was maintained at 34.5 degrees C. During surgical wound closure, patients were rewarmed. Intraoperative changes in tympanic membrane and skin temperatures and the incidence of postoperative shivering were compared among groups. Demographic and intraoperative variables were similar among groups. There were no significant differences in tympanic temperatures among groups at each point during the operation. Skin temperature 30 min after rewarming and just after tracheal extubation was significantly lower in the PG20 group than in the PG50 group. Postoperative shivering was more frequent in the PG20 group (43%) than in the control (13%) and PG50 (17%) groups. These results suggest that the intraoperative administration of PGE1 does not affect changes in core temperature during deliberate mild hypothermia and that PGE1 at a dose of 0.02 microg x kg(-1) x min(-1) may increase the occurrence of postoperative shivering. IMPLICATIONS: Deliberate mild hypothermia has been proposed as a means of providing cerebral protection during neurosurgical procedures. Vasodilating drugs may be used during deliberate mild hypothermia to maintain peripheral circulation and to enhance the cooling and rewarming rate. In the present study, however, we found no benefit from i.v. prostaglandin E1 administration during deliberate mild hypothermia in neurosurgical patients. PMID- 9972773 TI - The effects of clonidine and dexmedetomidine on human neutrophil functions. AB - Neutrophil functions are inhibited by various anesthetics. Clonidine and dexmedetomidine, alpha2-agonists, are often used as adjuncts to anesthesia. Thus, we conducted the current study to determine the effect of clonidine, dexmedetomidine, and xylazine at clinically (or veterinary anesthetically) relevant concentrations (and 10 and 100 times these concentrations) on several aspects of human neutrophil functions using an in vitro system. The three alpha2 agonists had no effects on chemotaxis, phagocytosis, or superoxide anion (O2-) production of neutrophils, except that the highest concentration of clonidine inhibited chemotaxis. Increases in intracellular calcium concentrations in neutrophils stimulated by chemotaxin were not influenced by clonidine, dexmedetomidine, or xylazine. Unchanged calcium concentrations may contribute to failure to modulate the neutrophil functions. In addition, these drugs did not scavenge O2- generated by the cell-free (xanthine-xanthine oxidase) system. This is the first report concerning the effect of clonidine or dexmedetomidine on human neutrophil functions. Our findings suggest that we may not have to take extra precautions in using the alpha2-agonists in patients with infection, but that we cannot expect these drugs to be prophylaxis against autotissue injuries whose pathogenesis includes activation of neutrophils. IMPLICATIONS: Neutrophils are involved in the antibacterial host defense system and autotissue injury. We found that clinically relevant concentrations of clonidine and dexmedetomidine do not affect chemotaxis, phagocytosis, or superoxide production by human neutrophils. These findings indicate that it may not be necessary to take special care in using alpha2-agonists in patients with infection, sepsis, or systemic inflammation. PMID- 9972774 TI - The effect of alpha2-adrenergic drugs on the activity of neurons in the rat nucleus raphe magnus in vitro. AB - The nucleus raphe magnus (NRM) is an important descending inhibitory system for pain transmission. We tested whether clonidine, an alpha2-adrenergic agonist, and yohimbine, an alpha2-adrenergic antagonist, modulate the activity of NRM neurons using extracellular recording in a rat brainstem slice preparation. Clonidine 1 20 microM increased firing frequencies (FF) in 22 (37%) and decreased FF in 6 (10%) spontaneously active neurons. Correlation between the concentrations of clonidine and FF changes was unremarkable. Eight spontaneously active neurons (13%) showed increases followed by decreases in FF with increasing doses of clonidine. The remaining 24 neurons (40%) showed no change in FF. Yohimbine 1 microM decreased FF in 38 spontaneously active neurons (58%), whereas the remaining 27 neurons (42%) showed no change in FF. In some neurons, yohimbine antagonized the increase or decrease in FF by application of clonidine. In three silent neurons (25%), clonidine (5 or 10 microM) induced firing activity, which stopped or decreased with the increasing doses of clonidine. In the remaining nine neurons (75%), clonidine did not induce firing activity. We conclude that activation and inhibition of alpha2-adrenergic receptors of NRM neurons augments and suppresses output of the descending inhibitory pain pathway. IMPLICATIONS: The nucleus raphe magnus is implicated in descending control of the nociceptive processes. We found that clonidine and yohimbine increased and decreased, respectively, the firing activity of a substantial number of nucleus raphe magnus neurons. Clonidine and may facilitate and yohimbine may reduce the outflow of the descending inhibitory pathway. PMID- 9972775 TI - Severe anaphylactic reaction to cisatracurium. PMID- 9972776 TI - The relationship between dynamic compliance and inspiratory flow. PMID- 9972777 TI - Ondansetron versus droperidol for postoperative nausea and vomiting. PMID- 9972778 TI - Selecting double-lumen tubes for small patients. PMID- 9972779 TI - Label and labeling are not interchangeable. PMID- 9972780 TI - Airway adjunct to an unanticipated difficult airway. PMID- 9972781 TI - The hemodynamic effects of pneumoperitoneum during laparoscopic surgery in healthy infants: assessment by continuous esophageal aortic blood flow echo Doppler. PMID- 9972782 TI - Vaporizer level obstruction detected by anesthetic vapor analysis. PMID- 9972783 TI - Use of the laryngeal mask during emergence from anesthesia in a patient with an unstable neck. PMID- 9972784 TI - An illuminating stylet as an aid for tracheal intubation via the intubating laryngeal mask airway. PMID- 9972785 TI - Increased chromosomal radiosensitivity in breast cancer patients: a comparison of two assays. AB - PURPOSE: It has been shown previously that sensitivity to the induction of chromosome damage by ionizing radiation is, on average, higher in G2 or G0 lymphocytes of breast cancer patients than of normal healthy controls. The authors suggested that elevated chromosomal radiosensitivity may be a marker for breast cancer predisposition. To investigate whether the G0 micronucleus assay is a true surrogate for the more demanding G2 metaphase assay, both tests have now been performed on the same blood samples from 80 patients. METHODS: For the G0 micronucleus assay, cells were exposed to 3.5 Gy 137Cs gamma-rays 6 h before mitogenic stimulation, treated with cytochalasin B at 24 h post-stimulation and harvested at 90 h. For the G2 assay, at 72 h after stimulation cells were given 0.5 Gy X-rays and harvested 90 min later. RESULTS: Previous observations were confirmed, now with much larger numbers of donors, in that approximately 40% of breast cancer patients showed elevated sensitivity in the G2 assay (135 patients, 105 normals) and 25% in the G0 assay (130 patients, 68 normals). However, there was no correlation between G2 and G0 sensitivity for the 80 patients tested (r = 0.001, p = 0.99). Most of the sensitive patients were either G2 or G0 sensitive, with only 4% sensitive in both assays. CONCLUSIONS: The results suggest that different mechanisms of chromosomal radiosensitivity operate in G2 and G0 cells and that, in general, each chromosomally radiosensitive patient is defective in only one such mechanism, possibly via mutation (or polymorphism) of a single gene. Such mutations may confer cancer predisposition, of low penetrance, in a substantial proportion of patients. PMID- 9972786 TI - X-ray-induced simple, pseudosimple and complex exchanges involving two distinctly painted chromosomes. AB - PURPOSE: To detect simple, pseudosimple and complex chromosome exchanges in X-ray induced aberrations involving two distinctly painted chromosomes. Each visibly complex two-paint exchange was analysed to determine the number of breaks and chromosomes necessary to derive the pattern. In addition, the number of associated paint junctions was scored to assess the frequency of non-reciprocal exchanges. MATERIALS AND METHODS: Metaphase spreads were prepared from a human primary fibroblast cell line irradiated with 2, 4 and 6 Gy 250kV X-rays. FISH painting was performed with distinctly labelled probes for chromosomes 1 and 2, and a pancentromeric probe. RESULTS: From a total of 78 two-paint exchanges observed, 35 were apparently simple, with no additional counterstain chromatin, and 43 were visibly complex with two-colour painting, of which 23 contained at least one pseudosimple exchange. A detailed analysis of the number of two-paint colour junctions showed that at least 50% of the visibly complex exchange patterns involved non-reciprocal exchanges. The simple and complex exchange dose response curves were considered to be linear and curvilinear respectively. CONCLUSION: The frequency of non-reciprocal rejoining events within complex exchanges is consistent with an interaction model based on the free exchange of multiple break-ends. In addition, the simple and complex exchanges have distinct dose-response curves, in agreement with previous data for single-painted exchanges corrected for pseudosimples. PMID- 9972787 TI - Is there a simple answer to the origin of complex chromosome exchanges? PMID- 9972788 TI - Inter-laboratory comparison of cytogenetic endpoints for the biomonitoring of radiological workers. AB - PURPOSE: The evaluation of different cytogenetic endpoints of radiation damage for the biomonitoring of contract workers temporarily employed at nuclear power plants. MATERIALS AND METHODS: Blood samples from six donors were irradiated in vitro with doses ranging from 0.1 to 2Gy 60Co gamma-rays. Compared were a conventional analysis for dicentrics, the conventional micronucleus (MN) assay, the centromere micronucleus assay using p82H and an alphaAllCen pancentromeric probe, and tricolour FISH with chromosome 2, 4 and 8 DNA probes for the scoring of translocations. RESULTS: Agreement in the number of MN between Giemsa-and propidium iodine fluorescence-stained preparations was obtained. The control samples showed higher centromere positivity for the MN after FISH with the p82H probe compared with the alphaAllCen probe. The MN results with both probes showed a slight but systematic increase in the number of centromere-positive MN with dose, indicating that radiation, although principally clastogenic, also has aneuploidogenic properties. The values of the genomic translocation frequency (FG) derived from the observed translocation frequencies were systematically higher than the dicentric yields. Comparing the sensitivity of the different methods with restriction of the scoring time to 1 day for biomonitoring purposes, the centromere micronucleus assay had the lowest dose detection limit (0.1 to 0.2 Gy). CONCLUSION: This study shows that at present only the centromere micronucleus assay can combine high sensitivity with a reasonable scoring time for the biomonitoring of relatively large populations. PMID- 9972789 TI - Chromosome aberrations induced by light ions: Monte Carlo simulations based on a mechanistic model. AB - PURPOSE: To investigate the mechanisms underlying the induction of chromosome aberrations by ionizing radiation, focusing attention on DNA damage severity, interphase chromosome geometry and the distribution of DNA strand breaks. METHODS: An ab initio biophysical model of aberration induction in human lymphocytes specific for light ions was developed, based on the assumption that 'complex lesions' (clustered DNA breaks) produce aberrations, whereas less severe breaks are repaired. It was assumed that interphase chromosomes are spatially localized and that chromosome break free-ends rejoin pairwise randomly; the unrejoining of a certain fraction of free-ends was assumed to be possible, and small fragments were neglected in order to reproduce experimental conditions. The yield of different aberrations was calculated and compared with some data obtained using Giemsa or FISH techniques. RESULTS: Dose-response curves for dicentrics and centric rings (Giemsa) and for reciprocal, complex and incomplete exchanges (FISH) were simulated; the ratio between complex and reciprocal exchanges was also calculated as a function of particle type and LET. The results showed agreement with data from lymphocyte irradiation with light ions. CONCLUSIONS: The results suggest that clustered DNA breaks are a critical damage type for aberration induction and that interphase chromosome localization plays an important role. Moreover, the effect of a given particle type is related both to the number of induced complex lesions and to their spatial distribution. PMID- 9972790 TI - S values are not a signature for a significant contribution of neutrons to the radiation dose received by atomic-bomb survivors. AB - PURPOSE: It has been proposed previously that the ratio of complete to incomplete translocations as seen by fluorescence in situ hybridization (FISH), the S value, can be a cytogenetic fingerprint of exposure to radiation of different qualities. Results from a previous study suggested that the S value is approximately 10 for sparsely ionizing radiations such as X- and gamma-rays, and 2 for densely ionizing radiations. Based on FISH data of atomic-bomb (A-bomb) survivors, which showed an S value of 3.25, a significant neutron component to A-bomb radiation was suggested. To examine the possibility, the present in vitro study was conducted using X-rays. MATERIALS AND METHODS: Human blood lymphocytes were exposed to X-rays and first metaphases were examined with FISH using DNA probes for chromosomes 1, 2 and 4. RESULTS: The S value was 3.16 for X-rays, which differs from approximately 10 as reported previously, and not larger than the 3.25 obtained from the blood lymphocytes of A-bomb survivors. CONCLUSIONS: S values seem to vary among laboratories even after exposure of cells to sparsely ionizing radiations. Data from this study show that S values are not a signature for a significant contribution of neutrons to the radiation dose received by A bomb survivors in Hiroshima. PMID- 9972791 TI - Measurement of DNA base damage in cells exposed to low doses of gamma-radiation: comparison between the HPLC-EC and comet assays. AB - PURPOSE: Two different methods aimed at measuring DNA damage were compared. Monocytes were exposed to 60Co gamma-rays and the level of DNA damage was determined using either the HPLC-EC or comet assay. MATERIALS AND METHODS: The alkaline comet assay was used in association with the Fpg and Endo III DNA glycosylases to estimate the amount of modified bases together with strand breaks and alkali-labile sites. The HPLC-EC analysis was performed to measure 8-oxo-7,8 dihydro-2'-deoxyguanosine (8-oxodGuo) levels in cells. RESULTS: A correlation between these assays allowed the determination of the steady-state level and the yield of Fpg sensitive sites (assimilated to 8-oxodGuo), which were estimated to be 0.18 per 10(6) bp and 0.044 per 10(6) bp per Gy, respectively. Similar levels of Endo III sensitive sites were found. For the strand breaks and alkali-labile sites, the background level was 0.26 per 10(6) bp and the yield 0.123 per 10(6) bp per Gy. DISCUSSION: The modified comet assay appears to be an appropriate tool to estimate DNA base damage in cells exposed to low doses of gamma-radiation. PMID- 9972792 TI - Replication in vitro and cleavage by restriction endonuclease of 5-formyluracil- and 5-hydroxymethyluracil-containing oligonucleotides. AB - PURPOSE: To investigate the biological consequences of 5-formyluracil (5-foU) and 5-hydroxymethyluracil (5-hmU). MATERIALS AND METHOD: The authors constructed 22 mer oligonucleotides containing a 5-foU or 5-hmU residue at the same sites. The effects of such modifications on the ability to serve as a template for DNA polymerase and on the cleavage by sequence-specific restriction endonuclease were examined. RESULTS: The Klenow fragment of DNA polymerase I and Thermus thermophilus DNA polymerase read through the sites of 5-foU and 5-hmU in the templates. 5-FoU directed the incorporation of dCMP in addition to dAMP opposite the lesion during DNA synthesis. The DNA polymerases incorporated only dAMP opposite the 5-hmU. The substitution of thymine by 5-foU within the recognition site of the restriction endonucleases HincII and SalI inhibited or prevented the cleavage by the enzymes, whereas the enzymes cleaved the 5-hmU-containing oligonucleotides at the same rate as the T-containing oligonucleotides. CONCLUSIONS: These results indicated that the 5-foU-A base pair is less stable than the T-A base pair and that 5-foU can form a base pair with C in addition to A. It was also demonstrated that the oxidation of thymine to 5-hmU does not result in substantial deterioration. PMID- 9972793 TI - DNA-PK-independent rejoining of DNA double-strand breaks in human cell extracts in vitro. AB - PURPOSE: To investigate the role of DNA-dependent protein kinase (DNA-PK) in the rejoining of ionizing radiation-induced DNA double-strand breaks (dsb). MATERIALS AND METHODS: This study employed previously described in vitro assays that utilize nuclei or 'naked' DNA prepared from agarose-embedded cells as a substrate and S-HeLa cell extracts as a source of enzymes. Rejoining of dsb in these assays is absolutely dependent on cell extract and it proceeds, under optimal reaction conditions, to an extent similar to that observed in intact cells. Results were confirmed in a plasmid-based assay for in vitro rejoining of dsb. RESULTS: It is shown that concentrations of wortmannin completely inhibiting DNA-PK activity profoundly affect the rejoining of dsb in vivo, but have no effect on dsb rejoining in vitro. Furthermore, fractionation of cell extracts using ammonium sulphate precipitation, generates protein fractions that are able to support dsb rejoining, despite the fact that they do not contain detectable amounts of either DNA-PKcs or Ku80. Efficient rejoining of dsb in vitro is also observed with extracts of MO59J cells that lack DNA-PK activity. Finally, rejoining of dsb remains unaffected by wortmannin in a plasmid-based assay, and is also detectable with extracts of MO59J cells. CONCLUSIONS: These findings are in contrast with genetic studies demonstrating a requirement for DNA-PK activity for efficient rejoining of dsb in vivo. The difference between in vitro and in vivo results may not be attributed to chromatin structure since wortmannin was without an effect when using nuclei as a substrate. It is speculated that the differences between in vivo and in vitro results can be explained either by assuming the operation of multiple pathways in dsb rejoining, some of which do not require DNA-PK, or by postulating a purely regulatory/damage-sensing role for DNA-PK in intact cells but no direct involvement in dsb rejoining. PMID- 9972794 TI - A comparison of the radiosensitivity of relaxed and supercoiled plasmid DNA. AB - PURPOSE: The aim of the work was to compare critically the radiosensitivity of the supercoiled and relaxed forms of a plasmid DNA system commonly used in DNA damage assays. MATERIALS AND METHODS: The yields of single- (ssb) and double strand breaks (dsb) in pBR322 DNA over a range of scavenging capacities were measured in the presence of Tris after irradiation with a single pulse of 400 keV electrons. The response was compared with DNA that had been given a preliminary dose of gamma-rays such that an average of one ssb per molecule was present. RESULTS: The yields of dsb were found to be enhanced in the pre-irradiated DNA when Tris was present during irradiation at concentrations varying between 10 and 100 mmol dm(-3) with a maximal enhancement ratio of 1.6 at 80 mmol x dm(-3) Tris. This increased yield was not observed when both the pre-irradiation and the experimental doses were given by gamma-irradiation. The increased response was not found in DNA that had been enzymatically relaxed by the introduction of a nick in each molecule using the enzyme gpII. CONCLUSIONS: The observations suggest that the conformation per se does not influence the radiosensitivity. The enhanced yields observed in the gamma-ray pre-irradiated DNA with pulsed irradiation appear to be a consequence of the high dose rate used. A proposed explanation is that the combination of high dose levels (< or =1500 Gy) and short irradiation times (approximately 5 ns) would allow some 'spurs' to overlap and it is proposed that the enhanced yields of dsb are related to this. PMID- 9972795 TI - 4-Amino-1,8-naphthalimide: a novel inhibitor of poly(ADP-ribose) polymerase and radiation sensitizer. AB - PURPOSE: Poly(ADP-ribose) polymerase (PARP; EC 2.4.2.30) is a chromatin-bound enzyme which is known to regulate chromatin structure by poly(ADP-ribosyl)ation of nuclear proteins, to facilitate DNA base excision repair, and to contribute to cellular recovery following DNA damage. Because inhibitors of PARP are able to potentiate the cell-killing effects of some DNA-damaging agents and to inhibit the repair of induced DNA strand breaks, such compounds may enhance the anti tumour efficacy of radiotherapy or cytotoxic drug treatment. The PARP-inhibitory effects and radiosensitization of a new compound, 4-amino-1,8-naphthalimide (ANI), were examined. MATERIALS AND METHODS: The inhibition of radiation-induced poly(ADP-ribosyl)ation (50 Gy; 60Co gamma-radiation) was evaluated by immunofluorescence assay using MoAb 10H directed against poly(ADP-ribose). Cell survival was assessed by colony forming assay (CFA) to determine the cytotoxicity of radiosensitization potential in exponentially growing hamster lung fibroblasts (V79), rat prostate carcinoma (R3327-AT1) and human prostate carcinoma (DU145) cells. RESULTS: At concentrations above 30 nmol x dm(-3) ANI, radiation-induced poly(ADP-ribose) was not detectable by immunofluorescence in V79, AT1 and DU145 cells. At the highest concentration tested for chronic exposure (20 micromol x dm(-3)), ANI was not cytotoxic and significantly potentiates the cytotoxicity of gamma-irradiation. The level of radiation enhancement was directly proportional to drug concentration. Survival curves for the three cell lines using 20 micromol x dm(-3) ANI revealed sensitizer enhancement ratios of 1.3 for V79, 1.5 for AT1 and 1.3 for DU145. CONCLUSIONS: In living cells, ANI is about 1000-fold more potent at inhibiting PARP activity compared with 3-aminobenzamide (3-ABA). CFA studies demonstrated that ANI is a radiation sensitizer at non-toxic and lower concentrations (20 micromol x dm(-3)) than 3-ABA (10 mmol x dm(-3)). PMID- 9972797 TI - In vivo exposure of rats to GSM-modulated microwaves: flow cytometry analysis of lymphocyte subpopulations and of mitogen stimulation. AB - The effects of GSM-modulated microwaves on lymphocyte sub-populations of Sprague Dawley rats and their normal mitogenic responses were investigated using flow cytometry analysis and a colorimetric method. No alterations were found in the surface phenotype of splenic lymphocytes or in their mitogenic activity, indicating that low-level pulsed microwaves do not seem to affect the integrity of the immune system. PMID- 9972796 TI - Bleomycin versus OH-radical-induced malonaldehydic-product formation in DNA. AB - PURPOSE: To compare the actions of bleomycin and ionizing radiation on DNA regarding the formation of malonaldehyde-like products. MATERIALS AND METHODS: Calf thymus DNA was treated with iron/bleomycin or gamma-radiation at pH 7. Products were analysed by HPLC. The thiobarbituric-acid reactivity of the samples was determined directly or after HPLC by post-column derivatization. ESI mass spectra were taken on-line following HPLC. RESULTS: Malonaldehyde and malonaldehyde-like products as detected by the sensitive 2-thiobarbituric acid (TBA) assay are formed in gamma-irradiated DNA and thymidine solutions as well as upon treatment of DNA with bleomycin/iron. In gamma-irradiated DNA solutions in the presence of oxygen, no base propenals were detected, and the major TBA-active product was malonaldehyde. In the gamma-radiolysis of thymidine, thymine propenal was formed only in traces (not more than 0.07 per cent of the OH-radical yield). Malonaldehyde was practically absent after treatment with bleomycin; three other TBA-active products were seen by HPLC which have been identified as the cytosine, thymine, and adenine propenals. Guanine propenal was not detected under our conditions. CONCLUSIONS: The absence of these base propenals upon gamma radiolysis implies that although the initiating step of OH-radical and bleomycin action [i.e. H-abstraction at C(4')] may be the same, the bleomycin-iron complex must participate in subsequent steps en route to the base propenals. It is proposed that the bleomycin pathway may involve the interaction of the C(4') peroxyl radical with the 'spent' bleomycin-iron complex by ligand exchange, under formation of a bleomycin-iron-peroxyl-radical complex, Blm(Fe4+,*OOR), which then decomposes by heterolysis into the alkoxy cation precursor +OR of the base propenal and reconstitution of the bleomycin-iron complex Blm(Fe,O)3+, i.e. gives rise to base propenal formation without the involvement of a C(4')-hydroperoxide. PMID- 9972798 TI - Frequency of micronuclei in the blood and bone marrow cells of mice exposed to ultra-wideband electromagnetic radiation. AB - PURPOSE: To investigate the extent of genetic damage in the peripheral blood and bone marrow cells of mice exposed to ultra-wideband electromagnetic radiation (UWBR). MATERIALS AND METHODS: CF-1 male mice were exposed to UWBR for 15 min at an estimated whole-body average specific absorption rate of 37 mW x kg(-1). Groups of untreated control and positive control mice injected with mitomycin C were also included in the study. After various treatments, half of the mice were killed at 18 h, and the other half at 24 h. Peripheral blood and bone marrow smears were examined to determine the extent of genotoxicity, as assessed by the presence of micronuclei (MN) in polychromatic erythrocytes (PCE). RESULTS: The percentages of PCE and the incidence of MN per 2000 PCE in both tissues in mice killed at 18 h were similar to the frequencies observed in mice terminated at 24 h. There were no significant differences in the percentage of PCE between control and the mice with or without UWBR exposure; the group mean values (+/- standard deviation) were in the range of 3.1+/-0.14 to 3.2+/-0.23 in peripheral blood, and 49.0+/-3.56 to 52.3+/-4.02 in bone marrow. The mean incidence of MN per 2000 PCE in control and in mice with or without UWBR exposure ranged from 7.7+/-2.00 to 9.7+/-2.54 in peripheral blood and 7.4+/-2.32 to 10.0+/-3.27 in bone marrow. Pairwise comparison of the data did not reveal statistically significant differences between the control and mice with or without UWBR exposure groups (excluding positive controls). CONCLUSION: Under the experimental conditions tested, there was no evidence for excess genotoxicity in peripheral blood or bone marrow cells of mice exposed to UWBR. PMID- 9972799 TI - Differential learning impairments produced by prenatal exposure to ionizing radiation in mice. AB - PURPOSE: To investigate the behavioural effects of prenatal irradiation on different days of gestation on the performance of two learning tasks by adult mice. MATERIALS AND METHODS: CD1 mice were exposed in utero to 1 Gy of 250 kV X rays on gestational days 13, 15 or 18. Other animals were sham-exposed. Male mice were tested as adults in a radial arm maze on two learning tasks considered dependent upon either spatial memory or visual associative memory. RESULTS: Performance of the animals on the tasks was a function of the day on which exposure occurred. Compared with sham-exposed animals, exposure on day 18 produced a highly significant deficit in performance on the spatial task, and a small improvement in the visually cued task. Exposure on day 15 produced no deficit in performance on the spatial task, but a highly significant deficit in the cued task. Exposure on day 13 produced no significant deficits on either task. CONCLUSIONS: These differential effects on performance appear to be consistent with radiation-induced insult to different memory systems within the developing mouse brain. These and further studies will help provide better estimates of the risks of radiation at different times during gestation on cognitive function in humans. PMID- 9972800 TI - Observations on the pollical palmar interosseous muscle (of Henle). AB - Questions about the existence of a "pollical" (first) volar interosseous muscle have persisted since its description by Henle in 1858. A survey of current human anatomy texts and atlases reveals that the majority do not recognize a pollical volar interosseous muscle and therefore they identify only three palmar interossei. We examined the thumbs of 20 individuals of African and European origin in the human anatomy lab at University of the Witwatersrand (Johannesburg) and 15 individuals of European ancestry in the anatomy lab at the University at Stony Brook (New York). A pollical palmar interosseous muscle (PPIM) was found in 86% of individuals (17/20 of the Witwatersrand sample; 13/15 of the Stony Brook sample). Here, we offer a definition of the PPIM in an attempt to resolve the long-standing question of its existence and its relationship to the adductor pollicis obliquus and the deep head of flexor pollicis brevis. We suggest that the human hand usually possesses four palmar interossei as well as four dorsal interossei. PMID- 9972801 TI - Innervation of tracheal epithelium and smooth muscle by neurons in airway ganglia. AB - The neurochemical profiles of neurons in ferret tracheal ganglia has been characterized, but their projections to smooth muscle and epithelium in ferret trachea has not been examined. The purpose of this study is to determine the location of cell bodies that project VIP-, SP-, and NPY-containing fibers to the ferret tracheal smooth muscle and epithelium. Segments of ferret trachea were cultured for 0, 1, 3, or 7 days, some in the presence of 3 microm capsaicin. VIP, SP, or NPY nerve fiber density was measured using morphometric procedures. A retrograde tracer, rhodamine-labeled microspheres, identified neurons projecting to the epithelium. The density of SP fibers in the epithelium was reduced after culture, but VIP innervation was not different. In tracheal smooth muscle, the density of VIP- and SP-IR fibers was not different during the culture period, but NPY fiber density was reduced at all culture times. Capsaicin treatment did not affect nerve fiber density in the tracheal smooth muscle but produced a significant reduction in the density of epithelial VIP- and SP-IR nerve fibers after 1 day. Rhodamine-labeled microspheres were identified in VIP-containing nerve cell bodies of the ferret tracheal plexus. VIP innervation to the airway epithelium in ferret originates both from cell bodies in airway ganglia and cell bodies in sensory ganglia. The pathway from airway ganglia suggest the existence of a local reflex mechanisms initiated by epithelial irritation. PMID- 9972802 TI - Human radicular veins: regulation of venous reflux in the absence of valves. AB - In the literature it is generally assumed that venous reflux within the radicular veins is prevented by the presence of bicuspid valves and narrowing of the transdural part of these vessels. Recently, we performed a human cadaver study of the internal vertebral venous plexus. Surprisingly, a large number of radicular and perimedullary veins appeared to be filled with Araldite CY 221 mixture, after injection of this material into the vertebral venous system, implicating reflux via the radicular veins and suggesting insufficiency of the presumed anti-reflux mechanism. Therefore, it was decided to study the radicular veins in order to determine and to investigate the presence or absence of anti-reflux mechanisms within this system. The vertebral venous systems of ten fresh human cadavers, between 64 and 93 years of age, were injected with Araldite CY 221 mixture. After polymerization, all cadavers were dissected and the spinal nerve sheaths, including nerve roots, radicular veins and epidural veins, were excised as a whole. After macroscopical examination, serial sections (40 microm) were cut on a freezing microtome and stained in Von Gieson medium. Every third section was stained immunohistochemically with smooth muscle antigen (SMA), to visualize smooth muscle cells. In all cadavers, a number of intradural radicular veins was filled with Araldite. Employing microscopical examination, no bicuspid valves were found. However, four structures were encountered that might serve as ananti reflux-mechanism: 1) intravenous dural folds, 2) meandrous configuration, and 3) narrowing of the radicular veins at the point of penetration of the dura mater, and 4) varying numbers of smooth muscle fibers in the walls of the intradural and extradural parts of the radicular veins. Reflux via the radicular veins seems to be a physiological phenomenon. Structural valves have not been encountered during this study. Intravenous dural folds, meandrous configuration and narrowing of the transdural part of the radicular veins, and the presence of large numbers of smooth muscle cells in the radicular venous walls suggest the existence of a dynamic reflux-regulating system that has the ability to increase the intravascular resistance under conditions of venous hyperpression, in order to protect the spinal cord from venous pressure waves. Possibly, venous reflux via the radicular veins has a role in selective cooling of the spinal cord. PMID- 9972804 TI - Ultrastructure and lectin cytochemistry of the cloacal pelvic glands in the male newt Triturus marmoratus marmoratus. AB - The cloacal organ of Salamandridae species contains four glands: pelvic, dorsal, ventral, and Kingsbury's glands. Pelvic glands have been studied only by light microscopy with conventional methods, and consist of multiple tubular serous glands with a prismatic epithelium which contains numerous PAS positive secretory granules. The present report is an ultrastructural and lectin cytochemistry characterization of the pelvic glands of Triturus marmoratus marmoratus throughout the reproductive cycle. Our methods consisted of conventional electron microscopy, and colloidal-gold lectin cytochemistry of the following lectins: WGA, ConA, LcA, UEA-I, PNA, SBA, and HPA. In the prereproductive period, the glands showed a tall epithelium which consisted of two cell types, dark and clear cells, surrounded by elongated, myoepithelial cells. Both dark and clear cells showed the ultrastructural characteristics of secretory cells, and exhibited many secretory granules in the apical cytoplasm. Areas showing densely packed, degenerating cell organelles--which were not surrounded by membrane--were observed in the dark cells whereas the clear cells showed large heterolysosomes. In the postreproductive period the number of secretory granules decreased, the rough endoplasmic reticulum was less developed, and areas of degenerating organelles were absent. In addition, small basal cells appeared. The results of the lectin histochemistry study were similar in both reproductive periods. In the epithelial cells, the rough endoplasmic reticulum, the Golgi complex, and secretory granules exclusively labeled to ConA. In all cell types, the nuclei reacted to all lectins while the cytosol only reacted to LcA lectin. The ultrastructural and histochemical characteristics of the pelvic glands of T. marmoratus suggest that these glands could be homologous to the mammalian seminal vesicles and prostate. PMID- 9972803 TI - Dynamic expression of a native chondroitin sulfate epitope reveals microheterogeneity of extracellular matrix organization in the embryonic chick heart. AB - TC2 is a novel monoclonal antibody produced by in vitro immunization of splenocytes with a peanut agglutinin-positive fraction from extracts of prechondrogenic micromass cultures of chick limb mesenchyme. ELISA results demonstrated TC2 reactivity with a native epitope on a glycosaminoglycan (GAG) enriched in chondroitin-4-sulfate and with multiple intact proteoglycans, but not with other GAGs tested. TC2 immunohistochemical reactivity was abolished by pretreatment of sections with chondroitinase AC or preadsorption with chondroitin 4-sulfate GAG. Strong TC2 localization occurred throughout the developing heart at stage 9. As looping ensued, a graded reactivity was observed from lowest in the atrium to highest in the conotruncus that correlated well with versican localization. The superior atrioventricular cushion stained preferentially with TC2 as compared to the inferior cushion at stages 16-18. At these later stages TC2 patterns did not agree completely with anti-versican reactivity. By stage 23 there was a marked reduction in TC2 localization in the heart, however, strong reactivity remained at certain sites, including the conotruncus and in subcompartments of both atrioventricular cushions. A heterogeneous distribution of other native chondroitin sulfate glycosaminoglycan epitopes recognized by monoclonal antibodies d1C4 and CS-56 was observed as well. The distribution of the TC2 epitope usually did not overlap with d1C4 or CS-56 localization at the stages examined. Overall, the spatiotemporal characteristics of TC2 reactivity in the developing chick heart appear to correlate with subdomains of the endocardial cushions as well as with trabecular and atrial septal formation. PMID- 9972805 TI - Apoptotic cell death in artificially induced deciduoma of pseudopregnant mice. AB - Deciduoma induced by mechanical stimulation in pseudopregnant mice is similar to the decidua in normal pregnancy and it undergoes regression after a certain period. Therefore, we examined cell death in deciduomas which were induced by artificial stimulation. To analyze the regression mechanism of artificially induced deciduoma, DNA fragmentation, in situ 3'-DNA nick end labeling, and RT PCR were performed on day 6 to 14 of pseudopregnancy. DNA fragmentation appeared on day 8 and it increased to day 10 of pseudopregnancy in the traumatized uterine horn. A large number of apoptotic cells were found on day 10 in the periphery of deciduoma at the antimesometrial side. Deciduoma underwent degeneration on day 11 of pseudopregnancy. Expression of tumor necrosis factor-alpha (TNF-alpha) mRNA was high on days 8 and 10, then decreased, whereas the expression increased again on day 14. TNF-alpha protein was expressed from day 8 to day 12, showing a peak expression on day 10 when deciduoma reached maximum weight. Serum progesterone level was high in the traumatized pseudopregnant mice on day 6, then it gradually decreased. Life span of deciduoma was prolonged 4 days more by daily injection of progesterone. A reduction in serum progesterone coincides with TNF-alpha increase, resulting in an increase of apoptotic deciduomal cells at the regression period, and that the life span of deciduoma is prolonged by additive supply of progesterone. PMID- 9972806 TI - Co-localization of Rab3B and oxytocin to electron dense granules of the sheep corpus luteum during the estrous cycle. AB - Oxytocin and its carrier protein, neurophysin, are both associated with luteal secretory granules which migrate from the paranuclear region to the cell membrane where exocytosis takes place. Rab3 proteins are thought to be associated with membrane vesicles or granules undergoing exocytotic fusion with the plasma membrane. The objective of this study was to determine whether Rab3B is co localized with oxytocin within the same secretory granules of large luteal cells obtained from corpora lutea of 16 Merino cross ewes at day 3, 7, 12 or 15 of the estrous cycle using immunocytochemistry. The mean granule density (granules/microm3) was not significantly different (P > 0.05) between the days examined. Electron microscopic immunocytochemistry showed that oxytocin and Rab3B were co-localized to the secretory granules on all days evaluated. Rab3B immunostaining was primarily located within secretory granules scattered throughout the cytoplasm. The mean intensity of labelling (number of gold particles) for oxytocin per microm2 cytoplasmic luteal tissue was significantly decreased on day 15 compared to those observed on days 3, 7 and 12 of estrous cycle. No significant changes were observed in the mean intensity of the Rab3B label at the different times of the cycle. The present study provides evidence that a member of the subfamily of Rab proteins, Rab3B, is present and co localized with oxytocin in the same secretory granules of the ovine corpus luteum. These results implicate Rab3B protein directly or indirectly in the hormone secretory pathway of ovarian tissue. PMID- 9972807 TI - Organization of motoneurons in the dorsal hypoglossal nucleus that innervate the retrusor muscles of the tongue in the rat. AB - This anatomical investigation was prompted by the incomplete knowledge of the myotopic organization of the dorsal subdivison of the hypoglossal nucleus. Intrinsic muscle motoneurons were not segregated and labeled previously with regard to the lateral division of the hypoglossal nerve. Also, motoneuron number and cell size, in relation to the individual retrusor tongue musculature, were rarely addressed previously. Retrograde labeling ofretrusor muscle motoneurons in the dorsal subdivision of the rat hypoglossal nucleus was done. Cholera toxin conjugate horseradish peroxidase (CTHRP) was injected into the retrusor tongue muscles with only the lateral division of the hypoglossal nerve intact. The dorsal subdivision of the hypoglossal nucleus contained approximately 800 motoneurons ranging in cell body size from 19 to 41 microm. When either the styloglossus, hyoglossus, superior longitudinal, or inferior longitudinal muscle was isolated and injected with CTHRP, a separate motoneuron pool for each muscle was seen. The extrinsic muscle motoneurons, styloglossus and hyoglossus, were found rostrolateral and caudolateral respectively. In contrast, the intrinsic superior and inferior longitudinal muscle motoneurons were found more central and medial in the nucleus. Extrinsic muscle motoneurons were larger (approximately 30 microm) than intrinsic muscle motoneurons (approximately 26 microm; P < .0001). Intrinsic muscle motoneurons account for a great majority of the motoneurons in the dorsal aspect of the hypoglossal nucleus and their axons have been shown to be contained in the lateral (retrusor) division of the hypoglossal nerve. This study revealed the myotopic organization of the retrusor subdivision of the rat hypoglossal nucleus. PMID- 9972808 TI - Cross-linked features of mouse pelage hair resistant to detergent extraction. AB - Cross-linking defects in hair cuticle have been observed in certain rare human disorders (trichothiodystrophy, transglutaminase-deficient lamellar ichthyosis). The hypothesis being investigated is that defective cross-linking in the cuticle or other parts of the fiber is a feature of some mouse mutants in which the hair is sparse or appears structurally unsound. Pelage hair samples from 13 mouse mutants displaying defective hair were extracted with sodium dodecyl sulfate and dithiothreitol at neutral pH and examined by transmission electron microscopy. All samples were indistinguishable after extraction from normal hair fibers in appearance of the medulla and cortex. In the cortex, keratins were completely extractable, but material remaining at the cell boundaries was clearly evident. Cells of the medulla were largely unextracted, containing distinct nuclei and amorphous material in the cytoplasm. In two samples (from mice with the matted/flaky tail and naked mutations) cells of the cuticle, which readily detached from the fiber when incubated at 100 degrees C, were more extensively extracted than normal. Defective cross-linking is thus observable in a minority of mouse hair mutants. The observed perturbation of cross-linking in the cuticle was not accompanied by visible perturbation in the cortex or medulla, indicating that different proteins participate in cross-linking in the different cell types. PMID- 9972809 TI - Remodeling of chick embryonic ventricular myoarchitecture under experimentally changed loading conditions. AB - Adult myocardium adapts to changing functional demands by hyper- or hypotrophy while the developing heart reacts by hyper- or hypoplasia. How embryonic myocardial architecture adjusts to experimentally altered loading is not known. We subjected the chick embryonic hearts to mechanically altered loading to study its influence upon ventricular myoarchitecture. Chick embryonic hearts were subjected to conotruncal banding (increased afterload model), or left atrial ligation or clipping, creating a combined model of increased preload in right ventricle and decreased preload in left ventricle. Modifications of myocardial architecture were studied by scanning electron microscopy and histology with morphometry. In the conotruncal banded group, there was a mild to moderate ventricular dilatation, thickening of the compact myocardium and trabeculae, and spiraling of trabecular course in the left ventricle. Right atrioventricular valve morphology was altered from normal muscular flap towards a bicuspid structure. Left atrial ligation or clipping resulted in hypoplasia of the left heart structures with compensatory overdevelopment on the right side. Hypoplastic left ventricle had decreased myocardial volume and showed accelerated trabecular compaction. Increased volume load in the right ventricle was compensated primarily by chamber dilatation with altered trabecular pattern, and by trabecular proliferation and thickening of the compact myocardium at the later stages. A ventricular septal defect was noted in all conotruncal banded, and 25% of left atrial ligated hearts. Increasing pressure load is a main stimulus for embryonic myocardial growth, while increased volume load is compensated primarily by dilatation. Adequate loading is important for normal cardiac morphogenesis and the development of typical myocardial patterns. PMID- 9972810 TI - Developmental spectrum of cardiac outflow tract anomalies encompassing transposition of the great arteries and dextroposition of the aorta: pathogenic effect of extrinsic retinoic acid in the mouse embryo. AB - We previously reported that retinoic acid shows a dose-dependent differential induction of various cardiac outflow anomalies: transposition of the great arteries is induced mainly by a high dose (70 mg/kg) and dextroposition of the aorta by a low dose (40-60 mg/kg; Yasui et al., 1995). We subsequently delineated the aberrant outflow tract septation process leading to the transposition (Yasui et al., 1997). The aim of the present study was to illustrate a spectrum of developmental abnormalities by examining mouse embryos treated with a low dose of retinoic acid and comparing them with embryos administered a high dose. We employed in situ observation on live embryos to discern the blood flow streams and scanning electron microscopy to clarify the internal structure. The embryos treated with a low dose of retinoic acid showed several basic phenotypes common to the high dose retinoic acid group, although variable and relatively mild, such as hypoplasia and dysplasia in the proximal outflow cushions, decreased counter clockwise rotation in the distal outflow tract, and deviation of the edges of the developing outflow septum. In typical cases, the right-sided edge of the developing outflow septum shifted ventrally by various degrees, allowing for the right ventricle-to-aorta pathway, whereas the left-sided edge preserved the continuity with the interventricular septum, as in the normal embryo. These findings indicate that morphogenesis of dextroposition of the aorta and transposition of the great arteries are not only distinct but also show some basic pathways in common. PMID- 9972811 TI - Wall cytoarchitecture of the rat ciliary process microvasculature revealed with scanning electron microscopy. AB - Ciliary process vasculature has an important role in aqueous humor production. There have been, however, few reports describing the overall cytoarchitecture of ciliary process vasculature. The wall cytoarchitecture of microvessels in the rat ciliary process was elucidated by scanning electron microscopy after removal of ciliary epithelia and connective tissue components with HCl hydrolysis. Utilizing characteristics of cellular morphology and vessel diameters, several vascular components were identified along the vascular tree: 1) arterial iridociliary circles (30-60 microm in outer diameter), containing a compact layer of circularly oriented spindle-shaped smooth muscle cells; 2) the proximal part of the radial ciliary arteriole (10-25 microm), containing a less compact layer of circularly oriented branched-smooth muscle cells and spindle-shaped smooth muscle cells; 3) a middle part of the radial ciliary arteriole (20-35 pm), with circularly oriented branched-smooth muscle cells and irregularly oriented stellate cells with ramifying projections; 4) a distal part of the radial ciliary arteriole (10-20 microm), possessing irregularly oriented stellate cells with ramifying projections; 5) marginal venules (15-20 microm), with spidery pericytes possessing highly ramifying and overlapped projections; 6) capillaries in the ciliary process (4-7 microm), with widely scattered pericytes having longitudinal and several circular projections; 7) venules in the posterior basal region of the ciliary process (greater than 5 microm), with widely scattered pericytes having a few thin projections. From arterial iridociliary circles to venules in the basal region of ciliary process, seven parts could be recognized by wall cytoarchitecture, which was discussed in relation with the function. PMID- 9972812 TI - Parathyroids and ultimobranchial bodies in monotremes. AB - Only scant information is available in the scientific literature on the parathyroids and ultimobranchial bodies in the primitive mammals, the echidna (Tachyglossus aculeatus) and platypus (Ornithorhynchus anatinus). The major aim of this paper is to describe the morphology of the monotreme parathyroid gland and to compare it with parathyroids in mammals and reptiles. The gross anatomy and light microscopic structure of the ultimobranchial body, thymus, and thyroid are also given. Animals were dissected and routine light and electron microscopic techniques used to examine the microscopic morphology. The locations of parathyroid hormone, calcitonin and calcitonin gene-related peptide in tissue sections were identified by immunostaining. Monotremes have one pair of parathyroid glands located in the thorax and they are often associated with thymic tissue but never with the thyroid which is also present in the mediastinum. Ultimobranchial bodies are ventrolateral to the commencement of the trachea. Thymic lobules with Hassall's corpuscles are scattered in the fibrofatty tissue of the mediastinum and the ventral surface of the pericardium. Histologically, principal cells, water-clear cells, and non-secretory cells were identified in the parathyroid glands. Principal cells showed polarity and had microlamellar projections that formed intercellular canaliculi. Non-secretory cells had features similar to those of thymic epithelial reticular cells. Immunostaining of parathyroid hormone showed a diffuse distribution in parathyroid principal cells and none in ultimobranchial bodies. Identification of the ultimobranchial bodies was confirmed by immunostaining. The monotreme parathyroid gland, ultimobranchial bodies and thyroid show reptilian as well as mammalian features. PMID- 9972813 TI - Effect of single and periodic contusion on the rat soleus muscle at different stages of regeneration. AB - This work analyzed the rat soleus muscle after single and recurrent contusions at different stages of regeneration. A noninvasive contusion was produced by a type of drop-mass equipment. The posterior region of the right hind limb received a trauma and both right and left soleus muscles were analyzed 1, 4, and 6 days after a single contusion (1x), and 6 and 30 days after periodic contusions (10x, one trauma per week for 10 weeks). Single contusion: there was no significant difference between right and left soleus muscle weight. All animals showed abundant signs of acute damage in the right soleus. AChE activity was identified in regeneration segments of the right soleus. Periodic contusions: there was an increase in the right soleus muscle weight (alpha = 5%) only in the animals evaluated 6 days after periodic contusions. The right soleus muscle showed a high incidence of chronic signs of damage, such as split fibers and a centralized nucleus, which predominated when compared with the acute signs. Right soleus muscles showed split fibers with AChE activity in both the proximal and middle regions. There was no difference in the incidence of muscle fiber types (I, II, and IIC) between right and left soleus muscles after periodic contusions. Skeletal muscle contusion is common in humans, especially in sport activities, where repetitive traumas are also frequent. The results of this work indicate that despite the regeneration process there is an important change in the morphological aspect of regenerated muscle fibers, which possibly affect muscle performance. PMID- 9972814 TI - Monoclonal antibody GL1 and its possible involvement in the morphogenesis of the otic vesicle. AB - In a previous study, a monoclonal antibody (MAB) named GL1 was identified that is expressed in a precise pattern during gastrulation and early neurulation stages in chick embryos. In this article we have further investigated the expression pattern of this MAB in the chick embryo. GL1 antigen is present in several organs that seem not to be related developmentally. Among them, GL1 is present during the early steps of the otic placode formation, in the pharyngeal endoderm, in some neural crest cells, in the somites, and in the ventricular surface of the nervous system. The distribution in the nervous system is well patterned with two broad lines of expression in the ventricular side of the metencephalic region, a unique and centered expression in the border between the metencephalon and the myelencephalon and again in two lines running along the myelencephalon and the rostral spinal cord. Additionally, GL1 can be induced by members of the FGF family, and we have used this system to elucidate its role in otic placode formation. The results obtained reveal that GL1 can be a useful marker for the study of developmental processes in the endoderm, the otic anlage, and the apical surface of the nervous system. Biochemical analysis of the antigen recognized by this MAB must be carried out to elucidate the molecular nature of the antigen. PMID- 9972815 TI - Histochemical study of magellanic penguin (Spheniscus magellanicus) minor salivary glands during postnatal growth. AB - The histological and histochemical features of the minor salivary glands during postnatal development have been generally associated with the type of food ingested. However, recent studies support the fact that these salivary glands develop independently of the diet; in fact, minor salivary glands have similar morphological and histochemical characteristics in adult individuals of species with different diet regimens. Thus, the aim of this study was to characterize the developmental morphology of the penguin minor salivary glands and to contrast them with minor salivary glands of other species. The tongue, palatine, and mouth cavity (bottom) minor salivary glands of newborn, 1- to 20-day-old, and adult magellanic penguins were studied with hematoxylin-eosin, periodic acid-Schiff, alcian blue, toluidine blue, and lectin histochemistry. Minor salivary glands were present at all ages, although they were only moderately developed in animals less than 15 days old. After this age, glands were abundant in all age groups; in addition, cells from the glandular epithelium were functionally mature and secreted mucins. Nevertheless, in newborn to 15-day-old penguins, mucins were located only at the apical cytoplasm of mucous cells. In all ages, mucous cells displayed periodic acid-Schiff-positive, alcianophilic, and metachromatic reactions; among mucous cells, other orthochromatic cells appeared interspersed. From 15 days on, histochemical reactions became more intense until adulthood, and the cytoplasm of secretory cells was filled with glycoproteins and sulfomucins. Moreover, lectins bound to different oligosaccharides in mucous cells, depending on the stage of maturation of the glands. In conclusion, penguin minor salivary glands are already present at birth, and show progressive and quantitative increases in mucous secretion during postnatal development. These changes are necessary not only for nutrient ingestion, but also for nonimmune protection of the buccal cavity. PMID- 9972816 TI - A philosopher looks at neuroscience. AB - The last two centuries, and the last fifty years in particular, have seen a dramatic increase in our understanding of the brain. More recently, philosophers have rekindled the debate about the nature of the mind and have begun to ask how and to what extent the features of the conscious mind, of the self, can be described in solely neurobiological terms. This essay describes a few ways in which neuroscientific research has changed the way philosophers think about the mind and also suggests some ways in which the methods and questions of philosophers might affect neuroscience. PMID- 9972817 TI - Adenoviral-mediated gene transfer to enhance neuronal survival, growth, and regeneration. PMID- 9972818 TI - Rat model of perinatal hypoxic-ischemic brain damage. AB - To gain insights into the pathogenesis and management of perinatal hypoxic ischemic brain damage, the authors have used an immature rat model which they developed many years ago. The model entails ligation of one common carotid artery followed thereafter by systemic hypoxia. The insult produces permanent hypoxic ischemic brain damage limited to the cerebral hemisphere ipsilateral to the carotid artery occlusion. The mini-review describes recently accomplished research pertaining to the use of the immature rat model, specifically, investigations involving energy metabolism, glucose transporter proteins, free radical injury, and seizures superimposed upon cerebral hypoxia-ischemia. Future research will focus on molecular mechanisms of neuronal injury with a continuing focus on therapeutic strategies to prevent or minimize hypoxic-ischemic brain damage. PMID- 9972819 TI - Post-transcriptional regulation of the peripheral myelin protein gene PMP22/gas3. AB - The peripheral myelin protein PMP22 gene has been described as a growth arrest specific gene gas3 and has been identified as disease gene of various demyelinating neuropathies. The gene consists of two highly conserved alternative noncoding 5'-exons la (CD25) and 1b (SR13), respectively. Differential expression patterns of these transcripts in vivo and in vitro suggest a very complex mode of PMP22 gene regulation, which cannot be explained merely by transcriptional control. In fact, the PMP22 gene is regulated on different post-transcriptional levels. While reverse transcriptase polymerase chain reaction (RT-PCR) analyses revealed no alterations in stability for both PMP22 transcripts in randomly growing Schwann cell cultures of rat sciatic nerve for at least 8 hours, in serum induced synchronized cultures of resting cells we observed a specific cell cycle regulated degradation of both transcripts. We further prepared diverse PMP22/CAT fusion genes to study the influence of the alternative 5'UTRs on PMP22 translation. Transient transfection of NIH3T3-fibroblasts and rat Schwann cells demonstrated that the alternative 5'UTRs (CD25 and SR13) and the 3'UTR exert differential regulatory influences on the translation efficiency. PMID- 9972820 TI - Septohippocampal adaptive GABAergic responses by AF64A treatment. AB - A cholinergically disrupted laboratory animal has been produced by administration of the cholinotoxin ethylcholine aziridinium mustard (AF64A), which produced a dysfunction in the cholinergic forebrain system. After AF64A treatment, a reduction of choline acetyl transferase (ChAT) activity was measured in the hippocampal regions. ChAT activity was preferentially reduced in tissue samples of the dorsal with respect to the ventral hippocampus, and concomitantly with this reduction, a compensatory increase in ChAT activity in the medial septum was found. Tissue gamma-aminobutyric acid (GABA) content in the hippocampal and septal brain areas was not affected by AF64A, indicating a specific effect on the cholinergic septohippocampal projection. The rate of GABA accumulation induced by aminooxyacetic acid administration was higher in the dorsal hippocampus and medial septum of AF64A-treated animals, but not in their ventral hippocampus and lateral septum, where significant changes occurred in ChAT activity. Concomitantly with the changes in GABA metabolism, a significant Bmax increase and Kd reduction of 3H-flunitrazepam binding in the hippocampus of AF64A-treated animals were associated with changes in the ChAT activity. This finding suggests an increase of GABA input on the cholinergic somas of the medial septum and an uncompensated GABAergic interneuron activity in the hippocampus. In this study, we present an adaptive mechanism of homotypic compensatory metabolism by cholinergic somas, and a heterotypic response of the GABAergic septohippocampal projection system, which was elicited by AF64A administration. PMID- 9972821 TI - Differential regulation of glial cell line-derived neurotrophic factor (GDNF) expression in human neuroblastoma and glioblastoma cell lines. AB - Human SK-N-AS neuroblastoma and U-87MG glioblastoma cell lines were found to secrete relatively high levels of glial cell line-derived neurotrophic factor (GDNF). In response to growth factors, cytokines, and pharmacophores, the two cell lines differentially regulated GDNF release. A 24-hr exposure to tumor necrosis factor-alpha (TNFalpha; 10 ng/ml) or interleukin-1beta (IL-1,; 10 ng/ml) induced GDNF release in U-87MG cells, but repressed GDNF release from SK-N-AS cells. Fibroblast growth factors (FGF)-1, -2, and -9 (50 ng/ml), the prostaglandins PGA2, PGE2, and PGI2 (10 microM), phorbol 12,13-didecanoate (PDD; 10 nM), okadaic acid (10 nM), dexamethasone (1 microM), and vitamin D3 (1 microm) also differentially effected GDNF release from U-87MG and SK-N-AS cells. A result shared by both cell lines, was a two- to threefold increase in GDNF release by db cAMP (1 mM), or forskolin (10 microM). In general, analysis of steady-state GDNF mRNA levels correlated with changes in extracellular GDNF levels in U-87MG cells but remained static in SK-N-AS cells. The data suggest that human GDNF synthesis/release can be regulated by numerous factors, signaling through multiple and diverse secondary messenger systems. Furthermore, we provide evidence of differential regulation of human GDNF synthesis/release in cells of glial (U-87MG) and neuronal (SK-N-AS) origin. PMID- 9972822 TI - Expression of three forms of nitric oxide synthase in peripheral nerve regeneration. AB - Nitric oxide (NO) is a short-lived molecule with messenger and cytotoxic functions in nervous, cardiovascular, and immune systems. Nitric oxide synthase (NOS), the enzyme responsible for NO synthesis, exists in three different forms: the neuronal (nNOS), present in discrete neuronal populations; the endothelial (eNOS), present in vascular endotheliun, and the inducible isoform (iNOS), expressed in various cell types when activated, including macrophages and glial cells. In this study, we have investigated the possible involvement of NO in Wallerian degeneration and the subsequent regeneration occurring after sciatic nerve ligature, using histochemistry and immunocytochemistry for the three NOS isoforms, at different postinjury periods. Two days after lesion, the three NOS isoforms are overexpressed, reaching their greatest expression during the second week. nNOS is upregulated in dorsal root ganglion neurons, centrifugally transported and accumulated in growing axons. eNOS is overexpressed in vasa nervorum of the distal stump and around ligature, and iNOS is induced in recruited macrophages. These findings indicate that different cellular sources contribute to maintain high levels of NO at the lesion site. The parallelism between NOS inductions and well-known repair phenomena suggests that NO, acting in different ways, may exert a beneficial effect on nerve regeneration. PMID- 9972823 TI - Role of desensitization and subunit expression for kainate receptor-mediated neurotoxicity in murine neocortical cultures. AB - The neurotoxic actions of kainate and domoate were studied in cultured murine neocortical neurons at various days in culture and found to be developmentally regulated involving three components of neurotoxicity: (1) toxicity via indirect activation of N-methyl-D-aspartate (NMDA) receptors, (2) toxicity mediated by alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptors, and (3) toxicity that can be mediated by kainate receptors when desensitization of the receptors is blocked. The indirect action at NMDA receptors was discovered because (5R, 10S)-(+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-im ine (MK-801), an NMDA receptor antagonist, was able to block part of the toxicity. The activation of NMDA receptors is most likely a secondary effect resulting from glutamate release upon kainate or domoate stimulation. 1-(4 Aminophenyl)-3-methylcarbamyl-4-methyl-3,4-dihydro-7,8-ethyle nedioxy-5H-2,3 benzodiazepine (GYKI 53655), a selective AMPA receptor antagonist, abolished the remaining toxicity. These results indicated that kainate- and domoate-mediated toxicity involves both the NMDA and the AMPA receptors. Pretreatment of the cultures with concanavalin A to prevent desensitization of kainate receptors led to an increased neurotoxicity upon stimulation with kainate or domoate. In neurons cultured for 12 days in vitro a small but significant neurotoxic effect was observed when stimulated with agonist in the presence of MK-801 and GYKI 53655. This indicates that the toxicity is produced by kainate receptors in mature cultures. Examining the subunit expression of the kainate receptor subunits GluR6/7 and KA2 did, however, not reveal any major change during development of the cultures. PMID- 9972824 TI - Interindividual differences in the levels of the glutamate transporters GLAST and GLT, but no clear correlation with Alzheimer's disease. AB - Alzheimer's disease is a common progressive neurodegenerative disease of unknown etiology. Several different pathological processes have been identified in the brains of Alzheimer patients. To determine if reduced glutamate uptake is a contributing factor, we have measured the levels of the glutamate transporter proteins GLAST (EAAT1) and GLT (EAAT2) in human autopsy samples. The postmortem proteolysis of these proteins turned out to be fairly rapid. Brains from 10 Alzheimer and 10 control patients were therefore obtained with a relatively short postmortem delay (5 hr on average). GLT (N-terminal and central parts), GLAST (C terminal), glial fibrillary acidic protein (GFAP) and inositol (1,4,5) triphosphate (IP3)-receptor immunoreactivities were determined in the cingulate and inferior temporal gyri by immunoblotting. The Na+-dependent "binding" of D [3H]aspartate and the glutamate uptake after solubilization and reconstitution in liposomes were determined for comparison. An individual variation in GLAST and GLT levels was found, but no significant correlation with Alzheimer's disease, except for a 14% lower ratio of N-terminal to central GLT immunoreactivity (P < 0.04). The levels of GLAST and GLT showed negative correlation in agreement with the idea that these proteins are differentially regulated. In conclusion, Alzheimer's disease brains can have both normal and reduced levels of GLAST and GLT. PMID- 9972825 TI - Electromagnetic fields influence NGF activity and levels following sciatic nerve transection. AB - Pulsed electromagnetic fields (PEMF) have been shown to increase the rate of nerve regeneration. Transient post-transection loss of target-derived nerve growth factor (NGF) is one mechanism proposed to signal induction of early nerve regenerative events. We tested the hypothesis that PEMF alter levels of NGF activity and protein in injured nerve and/or dorsal root ganglia (DRG) during the first stages of regeneration (6-72 hr). Rats with a transection injury to the midthigh portion of the sciatic nerve on one side were exposed to PEMF or sham control PEMF for 4 hr/day for different time periods. NGF-like activity was determined in DRG, in 5-mm nerve segments proximal and distal to the transection site and in a corresponding 5-mm segment of the contralateral nonoperated nerve. NGF-like activity of coded tissue samples was measured in a blinded fashion using the chick DRG sensory neuron bioassay. Overall, PEMF caused a significant decrease in NGF-like activity in nerve tissue (P < 0.02, repeated measures analysis of variance, ANOVA) with decreases evident in proximal, distal, and contralateral nonoperated nerve. Unexpectedly, transection was also found to cause a significant (P=0.001) 2-fold increase in DRG NGF-like activity between 6 and 24 hr postinjury in contralateral but not ipsilateral DRG. PEMF also reduced NGF-like activity in DRG, although this decrease did not reach statistical significance. Assessment of the same nerve and DRG samples using ELISA and NGF specific antibodies confirmed an overall significant (P < 0.001) decrease in NGF levels in PEMF-treated nerve tissue, while no decrease was detected in DRG or in nerve samples harvested from PEMF-treated uninjured rats. These findings demonstrate that PEMF can affect growth factor activity and levels, and raise the possibility that PEMF might promote nerve regeneration by amplifying the early postinjury decline in NGF activity. PMID- 9972826 TI - Effects of pulsed magnetic stimulation of GFAP levels in cultured astrocytes. AB - The present study evaluates the physiological effects of magnetic stimulation on astrocyte cultures. Cell cultures were exposed to pulsed magnetic stimulation (10 Hz, 10 sec) at the following levels: 0.10 tesla (T; Group A); 0.21 T (Group B); 0.42 T (Group C); and 0.63 T (Group D). Glial fibrillary acidic protein (GFAP) levels from immunoblots, total protein concentrations, and cellular morphology were analyzed at 0, 1, 3, 5, 7, 13, and 20 days poststimulation. Significantly higher GFAP levels were observed in Group D at day 3 (P = 0.0114). The change was transient as the GFAP levels quickly returned to control levels by day 5. No other significant changes in GFAP levels were observed. In comparison to control protein levels at day 0, concentrations from Groups B, C, and D were significantly lower (P < 0.006), whereas at day 3, Groups C and D were significantly higher (P < 0.02). Differences in astrocyte morphology due to magnetic stimulation were not observed. This study demonstrated that high intensity magnetic stimulation for only 10 sec induced a transient biological response. PMID- 9972827 TI - Cytokine-induced production of macrophage inflammatory protein-1alpha (MIP 1alpha) in cultured human astrocytes. AB - Macrophage inflammatory protein-1alpha (MIP-1alpha) is a member of a superfamily of inflammatory cytokines termed chemokines, and it has been implicated in the pathogenesis of several human diseases with inflammatory components. It has been known that MIP-1alpha plays a role in recruiting and activating mononuclear phagocytes in the central nervous system (CNS), and that astrocytes and microglia are sources of this chemokine. However, details of the regulation of MIP-1alpha production by these glial cells are not known. In the present study, expression of MIP-1alpha was determined in purified cultures of human astrocyte. MIP-1alpha mRNA levels in human astrocyte cell preparations were determined by reverse transcription polymerase chain reaction (RT-PCR) and amount of MIP-1alpha protein secreted into culture supernatants by human astrocytes was assayed by enzyme linked immunosorbent assay (ELISA). Under the unstimulated conditions, human astrocytes did not express MIP-1alpha message or protein, indicating that human astrocytes do not constitutively carry MIP-1alpha message. Following treatment with interleukin-1beta (IL-1beta), human astrocytes demonstrated increased message and protein expression for MIP-1alpha, while other immune modulators such as interferon-gamma (IFN)-gamma, tumor necrosis factor-alpha (TNF-alpha), granulocyte-macrophage colony-stimulating factor (GM-CSF), lipopolysaccharide, or phorbol ester (a protein kinase C activator) did not induce MIP-1alpha expression in human astrocytes. PMID- 9972828 TI - Unique retina cell phenotypes revealed by immunological analysis of recoverin expression in rat retina cells. AB - Among retina-specific proteins, recoverin is unique with respect to its cellular regulation in that it is found in rods, cones, some bipolar cells, and a rare population of cells in the ganglion cell layer. Recoverin is a calcium-binding protein which inhibits rhodopsin kinase from phosphorylating rhodopsin. Because cells in the inner layers of the retina do not contain rhodopsin kinase, arrestin, or other phototransduction proteins, it seems likely that recoverin has a different function in those cell types. To study this protein more fully, antibodies were generated against the entire mouse recoverin protein, as well as against peptides from the amino and from the carboxyl termini. These antibodies confirmed the localization of recoverin in vivo and clearly demonstrated, in culture, cells which were recoverin positive and rhodopsin negative. Surprisingly, two unique cell phenotypes were seen in cell culture which are not found in vivo. These cells are [rhodopsin(+), recoverin(-)] and [arrestin(+), recoverin(-)]. These phenotypes appear to represent the same population of cells and suggest that the recoverin gene can be regulated independent of genes for other phototransduction proteins. This cell culture system will be useful for investigating environments and factors which participate in the expression of the recoverin gene, and may identify regulatory features of the recoverin gene which cause it to be illicitly expressed in small-cell lung carcinomas in cancer associated retinopathy (CAR). PMID- 9972829 TI - Ultrastructural localization of cellular prion protein (PrPc) at the neuromuscular junction. AB - We examined the localization of the normal cellular isoform of prion protein (PrPc) in mammalian skeletal muscle. Using two anti-PrP antibodies, the neuromuscular junction (NMJ) was preferentially stained after immunohistofluorescence. The mouse, hamster, and human NMJ displayed a fluorescent signal specific for PrPc. Postembedding immunoelectron microscopy analysis performed in the mouse muscle showed that the PrPc-specific colloidal gold immunolabelling was concentrated over the sarcoplasmic cytoplasm. The membrane of the postsynaptic domain was devoid of gold particles, while a weak signal was occasionally observed close to the presynaptic vesicles of the terminal axons. These results indicate that the PrP gene is expressed in mammalian muscle at the NMJ. The subsynaptic sarcoplasm of the NMJ appears to be the privileged site where PrPc presumably associated with endosome membrane may play a role in either physiological activity or maintenance of the morphological integrity of the synapse. PMID- 9972830 TI - Self-reported body-rocking and other habits in college students. AB - A brief survey of eight motor habits, including body-rocking, was administered to two large samples of college undergraduates. A subsample was retested to establish survey reliability and validity. Those indicating engagement in body rocking were interviewed about their body-rocking. Two psychopathology instruments were administered. The general prevalence of self-described body rocking was higher than expected, and there were positive correlations among the eight habits. Body-rocking was usually related to negative affect and usually reported to begin during the school years and later. Many individuals said other family members engaged in body-rocking. Psychopathology assessments indicated higher levels of general distress and higher prevalence of Generalized Anxiety Disorder in this subsample compared with a group not reporting body-rocking. PMID- 9972831 TI - Dynamics of self-injurious behaviors. AB - Self-injurious behavior was examined in a case study of head-banging by an 8-year old girl with profound mental retardation and an autistic disorder. Trajectories of the arm movements and impact forces of the head blows were determined from a dynamic analysis of videotapes. Results revealed a high degree of cycle-to-cycle consistency in the qualitative dynamics of the limb motions, with one hand motions being faster than those with two hands (inphase and antiphase) and the motions with the helmet about 25% faster than those without the helmet. The impact force of SIBs as a percentage of body weights are near the low end of forces generated in boxing blows and karate hits. PMID- 9972832 TI - Competence and adjustment of siblings of children with mental retardation. AB - Adjustment and competence of siblings who had a brother or sister with mental retardation were compared to those of control siblings who had brothers or sisters with no disabilities. Results indicated no overall differences for internalizing disorders, externalizing disorders, or for self-esteem and competence based on group membership, gender, or gender match. However, boys with a brother or sister with mental retardation had difficulty in school functioning. In addition, a greater number of girls with brothers and sisters with mental retardation expressed their distress through internalization. PMID- 9972833 TI - Effects of formal and familial residential plans for adults with mental retardation on their aging mothers. AB - Data regarding future residential plans were collected from 141 mothers of adult children with mental retardation. Results demonstrate that greater caregiving burden was associated with more extensive planning for residence within the formal service system and less planning for residence with a family member. More frequent service use also predicted greater planning for future residence within the formal system. Planning for residence with a family member and higher functional ability on the part of the child significantly decreased the sense of worry mothers had about the child's future whereas plans for the child to reside within the formal system had no association with worry about the future. PMID- 9972834 TI - Architectural acoustics in residences for adults with mental retardation and its relation to perceived homelikeness. AB - Previous investigators examined how architectural features of residences for adults with mental retardation contributed to the visual appearance of homelikeness. Acoustical characteristics of 18 residences for people with mental retardation were examined here. As part of a concurrent study, college undergraduates rated photographs of rooms in each house for their apparent homelikeness. Reverberation times in living and dining rooms were negatively correlated with mean homelikeness ratings. The less homelike rooms had reverberation times that may interfere with speech perception for some people and that were comparable with those found in larger public rooms (e.g., lecture halls). The larger reverberation times in these rooms were the result of insufficient sound absorption by these rooms' furnishings. PMID- 9972835 TI - Maladaptive behavior differences in Prader-Willi syndrome due to paternal deletion versus maternal uniparental disomy. AB - Maladaptive behavior was compared across 23 people with Prader-Willi syndrome due to paternal deletion to 23 age- and gender-matched subjects with maternal uniparental disomy. Controlling for the higher IQs of the uniparental disomy group, deleted cases showed significantly higher maladaptive ratings on the Child Behavior Checklist's Internalizing, Externalizing, and Total domains as well as more symptom-related distress on the Yale-Brown Obsessive-Compulsive Scale. Across both measures, deleted cases were more apt to skin-pick, bite their nails, hoard, overeat, sulk, and withdraw. A dampening of symptom severity is suggested in Prader-Willi syndrome cases due to maternal uniparental disomy. Findings are compared to Angelman syndrome, and possible genetic mechanisms are discussed, as are implications for Prader-Willi syndrome and obsessive-compulsive behaviors. PMID- 9972836 TI - The Medicaid Home and Community-Based Waiver and supported employment. AB - The Medicaid Home and Community-Based (HCB) Waiver is the primary funding source for long-term care for individuals with developmental disabilities. Findings from a national survey of 48 state coordinators regarding waiver-funded supported employment services are presented. Very low utilization for this service was found, primarily due to limits on eligibility. However, respondents in 18 states reported large numbers of waiver participants receiving employment services under other service categories. Eleven states had waiting lists for waiver-funded supported employment, totalling three times those actually receiving services. Low reimbursement rates to provider agencies and disinterest of providers in using waiver funds were significant barriers to expansion of service capacity. PMID- 9972837 TI - Put your money where your mouth is: direct and indirect measures of attitude toward community integration. AB - We compared direct (a survey) and indirect (mock petition drive) attitude measures regarding opening a group home for people with mental retardation in the neighborhood. We systematically assigned participants to one of three groups: positively worded petition statement, negative statement, or no petition. All participants answered survey questions about attitudes toward persons with disabilities. Order of the measures was counterbalanced in the first two groups. The point-biserial correlation between the petition response and survey was a moderate .40, suggesting that the survey was not a very reliable predictor of how people would react when asked whether they agreed or objected to a group home being opened in their neighborhood. Survey responses were influenced further by the wording of the petition drive statement. PMID- 9972838 TI - Influence of different adrenoceptor agonists and antagonists on physostigmine induced yawning in rats. AB - In the present study, effects of adrenoceptor agonists and antagonists on physostigmine-induced yawning was investigated. Intraperitoneal (i.p.) injection of different doses of physostigmine (0.03, 0.05, 0.1, and 0.2 mg/kg) induced yawning in rats. The maximum response was obtained by 0.2 mg/kg of the drug. The alpha1-adrenoceptor agonist, phenylephrine, and the alpha2-adrenoceptor agonist, clonidine, decreased yawning induced by physostigmine. Prazosin and higher doses of phenoxybenzamine reduced the inhibitory effect of phenylephrine. Higher doses of yohimbine also reduced the clonidine response. The adrenoceptor antagonists, prazosin, phenoxybenzamine, and propranolol, did not significantly alter the physostigmine response. However, yohimbine, or lower doses of prazosin, decreased the physostigmine response. It may be concluded that alpha1- and alpha2 adrenoceptor stimulation decreases the physostigmine-induced yawning behavior in rats. PMID- 9972839 TI - Biochemical and behavioral effects of boldine and glaucine on dopamine systems. AB - The aporphine alkaloids boldine and glaucine have been reported to show "neuroleptic-like" actions in mice, suggesting that they may act as dopamine antagonists. We have found that in vitro boldine displaces specific striatal [3H] SCH 23390 binding with IC50 = 0.4 microM and [3H]-raclopride binding with IC50 = 0.5 microM, while the affinities of glaucine at the same sites are an order of magnitude lower. In vivo, however, 40 mg/kg boldine (i.p.) did not modify specific striatal [3H]-raclopride binding and only decreased [3H]-SCH 23390 binding by 25%. On the other hand, 40 mg/kg glaucine (i.p.) displaced both radioligands by about 50%. Behaviors (climbing, sniffing, grooming) elicited in mice by apomorphine (0.75 mg/kg s.c.) were not modified by boldine at doses up to 40 mg/kg (i.p.) but were almost completely abolished by 40 mg/kg glaucine (i.p.). In the apomorphine-induced (0.1 mg/kg s.c.) rat yawning and penile erection model, boldine and glaucine appeared to be similarly effective, inhibiting both behaviors by more than 50% at 40 mg/kg (i.p.). Boldine and glaucine, injected i.p. at doses up to 40 mg/kg, were poor modifiers of dopamine metabolism in mouse and rat striatum. These data suggest that boldine does not display effective central dopaminergic antagonist activities in vivo in spite of its good binding affinity at D1- and D2-like receptors, and that glaucine, although less effective in vitro, does appear to exhibit some antidopaminergic properties in vivo. PMID- 9972840 TI - Early withdrawal from repeated cocaine administration upregulates muscarinic and dopaminergic D2-like receptors in rat neostriatum. AB - The present results show an increase in locomotor activity 24 h following repeated cocaine administration only with the higher dose (10 mg/kg, i.p., daily for 1 week) compared to controls (administered with saline). Binding assays were done and the ligands used were [3H]N-methylscopolamine ([3H]-NMS), [3H]-SCH 23390, and [3H]-spiroperidol to determine muscarinic (M1- and M2-like), D1 and D2 receptors, respectively. Scatchard analyses revealed alterations in Bmax not only for muscarinic, but also for D2-like receptors that were significantly increased. On the other hand, no alterations were detected on D1-like receptors densities and dissociation constant values. However, the Kd value was significantly increased for D2 receptors. The changes in muscarinic receptors were observed predominantly on M2-like, which presented an increase of 84% with the 10 mg/kg, i.p., dose only. On D2-like receptors, increases of 63 and 54% were demonstrated with the doses of 5 and 10 mg/kg, i.p.. The preferential effects of cocaine on muscarinic and D2-like receptors were also demonstrated in vitro where decreases in [3H]-NMS and [3H]-spiroperidol binding were observed. The results indicate that the effects of cocaine on muscarinic and dopaminergic postsynaptic receptors are functions of dose, duration of treatment, and time of drug withdrawal. PMID- 9972841 TI - Behavioral effects of dopamine agonists and antagonists: influence of estrous cycle, ovariectomy, and estrogen replacement in rats. AB - The influence of the hormonal condition on the reactivity of central dopamine (DA) receptors was studied in male and in intact and ovariectomized (OVX) female rats. They were injected with selective DA agonists, acting either on D1 (SKF 38393, 2.5 or 10 mg/kg) or D2 receptors (PPHT, 31.3 or 125 microg/kg), or with selective DA antagonists, acting either on D1 (SCH 23390, 6.25 or 25 microg/kg), or D2 receptors (sulpiride, 10 or 40 mg/kg). The acquisition of an avoidance conditioning response (CAR) and the performance of some spontaneous motor behaviors were tested. Both D1 and D2 agonists and antagonists impaired the acquisition of CARs in diestrous, OVX, and male rats. Nevertheless, the effects of these drugs during estrus and in estradiol-primed OVX rats were different according to the drug and the dose injected. Whereas SKF 38393 failed to induce significative changes, PPHT and low doses of SCH 23390 and sulpiride improved the acquisition of CARS in those groups. The effects on conditioning were not accompanied with equivalent changes in spontaneous motor activity. Estradiol level fluctuations that occur in female rats within the estrous cycle or in OVX rats primed with estradiol would be responsive of changes in the response to DA agents. Although the reactivity of central DA systems is differentially affected by the hormonal condition of the rat, the precise mechanism of this modulatory action remains unknown. PMID- 9972842 TI - The expression of behavioral sensitization to amphetamine: role of CCK(A) receptors. AB - These studies investigated whether endogenous activation of CCK(A) receptors mediates the expression of amphetamine (AMP)-induced locomotor activity. In Experiment 1, locomotor activity was assessed in rats pretreated with the CCK(A) antagonist devazepide (0.001, 0.01, and 0.1 mg/kg) and subsequently injected with AMP (1.5 mg/kg). In Experiment 2, rats were administered AMP (1.5 mg/kg) once daily for 7 days. Following a 10-day withdrawal, locomotor activity was assessed following treatment with devazepide (0.001, 0.01, and 0.1 mg/kg) and AMP (0.75 mg/kg). In both studies, rats were classified as low (LR) or high (HR) responders based upon a median split of their locomotor response to a novel environment. Results from Experiment 1 showed that AMP potentiated the expression of locomotor activity, and this effect was most pronounced in HR rats. However, devazepide did not affect AMP-induced locomotion. Results from Experiment 2 demonstrated that chronic AMP pretreatment augmented the locomotor response to subsequent AMP challenge, and this effect was most pronounced in the HR group. Further, this augmented response was blocked by devazepide in HR rats. These findings constitute the first demonstration that endogenous CCK(A) receptor activation is an important substrate mediating AMP-induced locomotor activity in animals with a previous history of AMP treatment. PMID- 9972843 TI - Baclofen and AII 3-7 on learning and memory processes in rats chronically treated with ethanol. AB - The aim of this study was to determine the possible influence of baclofen, an agonist of the GABA(B) receptor on behavioral activity (recall, acquisition of conditioned reflexes) of angiotensin II fragment 3-7 (AII 3-7) in rats chronically treated with ethanol. Long-term (9 weeks) ethanol intoxication profoundly impaired learning and memory processes in all tests used. The GABA(B) receptor agonist baclofen (0.75 mg/kg i.p.) did not influence exploratory and motor activity in the control rats, but we observed a tendency (without significance) to decrease the psychomotor activity in the alcohol-intoxicated groups of animals, when it was injected together with AII 3-7 (2 microg i.c.v.). Baclofen did not influence the retrieval process in the passive avoidance recall, and when it was given together with AII 3-7 did not change the positive action of this fragment in control groups, but significantly enhanced its action in the animals chronically treated with ethanol. Baclofen showed significant improvement of acquisition in the active avoidance test only in the alcohol-intoxicated groups. Baclofen, injected together with AII 3-7, yielded important attenuation action of AII 3-7 in the control groups in the first 3 days of test, but did not produce any changes during the fourth and fifth day of the experiment. Baclofen did not provoke any changes in activity of AII 3-7 (when it was injected together) in the acquisition of the active avoidance test in the alcohol intoxicated groups of animals. PMID- 9972844 TI - FG 7142- and restraint-induced alterations in the ataxic effects of alcohol and midazolam in rats are time dependent. AB - The purpose of this study was to examine whether acute stress exposure would alter the ataxic properties of midazolam or ethanol in rats. Rats were administered either vehicle or FG 7142 (10 mg/kg) and placed back in their home cages, or placed in restraining tubes for 90 min. Three and one-half or 24 h following injection all subjects were then administered an ataxic dose of either ethanol or midazolam and after 10 min, motoric impairment was assessed by rotarod performance. Neither FG 7142 administration nor restraint had an impact on rotarod performance 3-1/2 h later for ethanol nor 24 h later in response to midazolam. However, midazolam-induced ataxia was significantly modified 3-1/2 h following both restraint and FG 7142 exposure. Similarly, at the 24-h time point, both manipulations had a significant effect on ethanol-induced motor incoordination. Importantly, prior exposure to FG 7142 and restraint was without effect on rotarod performance in saline-treated subjects. Functional alterations in behavioral reactivity to low doses of two classes of CNS depressants by the acute stress of restraint and/or FG 7142 administration suggest the anxiogenic nature of these stressors may be the critical factor. PMID- 9972845 TI - Sex and estrous cycle-dependent changes in neurosteroid and benzodiazepine effects on food consumption and plus-maze learning behaviors in rats. AB - Experiments were designed to investigate the influence of estrous cycle and gender of the rat on the effects of a gamma-aminobutyric acid type A (GABA(A)) receptor active neurosteroid, 3alpha-hydroxy-5alpha-pregnan-20-one (allopregnanolone), the benzodiazepine, triazolam, and a GABA(A) receptor antagonistic neurosteroid, delta5-androsten-3beta-ol-17-one sulfate (dehydroepiandrosterone sulfate), on food intake and elevated plus-maze learning behaviors. Allopregnanolone (0.25 mg/kg, s.c.) and triazolam (0.25 mg/kg, i.p.) produced a hyperphagic effect, while dehydroepiandrosterone sulfate (5 mg/kg, s.c.) elicited an anorectic effect. However, allopregnanolone was more potent in diestrous females, whereas triazolam exhibited significantly higher hyperphagic potency in estrus females. The extent of anorexia following dehydroepiandrosterone sulfate was alike in male and female rats. The triazolam- and allopregnanolone-induced hyperphagic effect was blocked by bicuculline (1 mg/kg, i.p.), a selective GABA(A) receptor antagonist. In contrast to triazolam, the hyperphagic effect of allopregnanolone was insensitive to flumazenil (5 mg/kg, i.p.), a benzodiazepine antagonist. Vehicle-treated diestrous rats displayed moderately higher latencies in the elevated plus-maze learning task than estrus or proestrus females. Although allopregnanolone and triazolam elicited equipotent learning deficits in plus-maze learning in male and female rats, the magnitude of impairment-induced by triazolam was significantly higher in diestrous females than proestrus females. Dehydroepiandrosterone sulfate enhanced memory performance only in male rats. Although the use of the elevated plus-maze as a learning paradigm with benzodiazepines and neurosteroids may be sensitive to changes in anxiety, the differential data suggest that neurosteroid induced effects are at least partly specific to learning behavior. These results confirm the role of estrous cycle and sex of rats in modifying the potency of neurosteroids and benzodiazepines on food consumption and learning and memory processes. PMID- 9972846 TI - Interleukin-1alpha injection into ventromedial hypothalamic nucleus of normal rats depresses food intake and increases release of dopamine and serotonin. AB - A microdialysis injector probe administered IL-1alpha into ventromedial hypothalamus (VMN) and concurrently measured release of dopamine (DA), DOPAC, 5 HT, and 5-HIAA. After baseline dialyses, six rats received 2-ng IL-1alpha and six rats received vehicle (1 microl saline) into VMN. Sixty minutes later, food was provided for 40 min while VMN monoamines were measured every 20 min. Vehicle had no significant effect on monoamines, their metabolites, or food intake. Food intake was significantly lower in IL-1alpha rats vs. controls (p < 0.01). Baseline levels of VMN monoamines (pg/10 microl dialysate) in IL-1alpha and vehicle groups were similar. DA and 5-HT rose immediately on injecting IL-1alpha and remained higher (p < 0.05) than basal during the first 60 min and 40 min sampling period, respectively. Levels of 5-HIAA also increased (p < 0.01). Eating decreased VMN DA in controls, and decreased VMN DOPAC in IL-1alpha-treated rats. During eating, VMN 5-HT in control rats significantly increased while increasing VMN 5-HIAA occurred in IL-1alpha rats. Findings show that an IL-1alpha pathophysiological dose injected into the VMN was associated with anorexia and significantly increased dopaminergic and serotonergic activities and suggest that enhanced VMN DA and 5-HT activities may be part of an IL-1alpha-initiated cascade involved in IL-1alpha-associated anorexia. PMID- 9972847 TI - NMDA-induced spinal hypersensitivity is reduced by naturally derived peptide analog [Ser1]histogranin. AB - N-methyl-D-aspartate (NMDA) receptor activation is thought to initiate a cellular cascade of events in the spinal cord that leads to neuronal hyperactivation and exaggerated persistent pain behaviors. Previous studies have demonstrated that implantation of adrenal medullary tissue into the spinal subarachnoid space reduces abnormal pain behaviors such as hyperalgesia and allodynia, possibly by intervening in the NMDA hyperexcitability cascade. Histogranin is a 15-amino acid peptide possessing NMDA receptor antagonist activity that has been isolated from adrenal medullary tissue. The present study examined the ability of stable analog [Ser1]histogranin to reduce abnormal pain-related behaviors induced in rats by direct activation of spinal NMDA receptors. The intrathecal injection of NMDA (5.0, 10.0, 20.0 nmol) produced significant thermal and mechanical hyperalgesia and tactile allodynia in a dose-related fashion. [Ser1]histogranin injected intrathecally prior to NMDA injections dose dependently attenuated or completely blocked hyperalgesia and allodynia. In addition, [Ser1]histogranin administration following NMDA-induction of abnormal pain behaviors reversed these effects. These results demonstrate that a naturally derived adrenal medullary neuropeptide can prevent and reverse NMDA-mediated spinal hyperexcitability. The distinct profile and robust activity of [Ser1]histogranin suggest novel alternative approaches in the management of pain and other CNS disorders involving abnormal excitatory neurotransmission. PMID- 9972848 TI - Cannabimimetic activity in rats and pigeons of HU 210, a potent antiemetic drug. AB - Preliminary behavioral experiments in rats with the cannabinoid agonist HU 210 (12.5-100 microg/kg i.p.) showed that it has a potent cannabimimetic profile similar to that of delta9THC; the drug dose dependently depressed locomotor activity, rearing, and grooming and elicited vocalization and circling at the highest doses. In subsequent studies on pigeons, HU 210 (12.5-50 microg/kg s.c.) confirmed its sedative effects; it also afforded protection against vomiting induced by cisplatin (7.5 mg/kg i.v.) and emetine (20 mg/kg s.c.) and emetine induced head shake. PMID- 9972849 TI - Rat locomotion and release of acetylcholinesterase. AB - In the substantia nigra acetylcholinesterase is released from the dopamine cells of the pars compacta independent of cholinergic transmission. In this study the effects of local and systemic amphetamine treatment were compared on acetylcholinesterase release in the rat substantia nigra in relation to concomitant behavior. Acetylcholinesterase release, measured "on-line" with a sensitive chemiluminescent system, was enhanced by amphetamine stimulation administered locally and could not be dissociated from simultaneous amphetamine induced circling behavior. On the other hand, amphetamine administered systemically resulted in a general increase in locomotor behavior followed by a subsequent increase in acetylcholinesterase release. The alternative scenario of an initial rise in acetylcholinesterase release, subsequently followed by enhanced movement, was never seen. Hence, movement can enhance release of acetylcholinesterase from the substantia nigra, whereas "upstream" local nigral events can affect acetylcholinesterase release and movement simultaneously. PMID- 9972850 TI - 5-HT2A and 5-HT2C/5-HT1B receptors are differentially involved in alcohol preference and consummatory behavior in cAA rats. AB - The present study aimed to investigate the role of serotonin 5-HT2A and 5-HT2C receptors in the control of alcohol preference and consummatory behavior in alcohol-preferring cAA rats. Effects of the 5-HT(2A/2C) receptor agonist, DOI, the 5-HT(2C/1B) receptor agonist, mCPP, the 5-HT(2A/2C) receptor antagonist, ritanserin, and the 5-HT2A receptor antagonist, MDL 100,907, on ethanol (EtOH, 10% v/v) preference and intake, as well as total fluid and food intake were evaluated in a 12-h limited-access two-bottle paradigm. DOI (0.3-3 mg/kg, i.p.) reduced EtOH intake and preference, but not total fluid or food intake; whereas mCPP (1-10 mg/kg, s.c.) reduced EtOH, total fluid, and food intake. Therefore, it is concluded that DOI induces a specific and selective antialcohol effect, whereas mCPP rather induces a general suppressive effect on consummatory behavior. Ritanserin (1-10 mg/kg, i.p.) did not affect EtOH intake and preference, nor total fluid and food consumption. MDL 100,907 (0.1-1 mg/kg, i.p.) induced only a small reduction of food intake at the highest dose tested. Pretreatment with ritanserin (3 mg/kg, i.p.) and MDL 100,907 (0.3 mg/kg, i.p.) blocked the effects of DOI (3 mg/kg, i.p.), but not those of mCPP (10 mg/kg, i.p.). It is suggested that activation of 5-HT2C and/or 5-HT1B receptors results in a general decrease of consummatory behavior, whereas activation of 5-HT2A receptors selectively decreases EtOH intake and preference, as assessed in the cAA rat model of alcoholism. PMID- 9972851 TI - The effects of the naltrexone implant on rodent social interactions and cocaine induced conditioned place preference. AB - Two experiments were conducted to determine the behavioral properties of the naltrexone implant on: 1) rodent social interactions; and 2) the appetitive properties of cocaine. Rats were surgically implanted with a naltrexone implant (placebo, 10 or 30 mg) and placed into an open field for the recording of social interactions. The naltrexone implants increased latency to initiate contact and decreased pinning, bouts of grooming, and crawl unders on all 7 days. Other rats were surgically implanted with naltrexone (60, 120, or 240 mg) and habituated to a two-chambered conditioned place preference apparatus. After 6 days of conditioning, place preference was computer recorded. Cocaine produced a dose dependent conditioned place preference in the rats implanted with placebo or 60 mg of naltrexone. The 120 and 240 mg naltrexone implants blocked the emergence of cocaine-induced place preference. The results indicate that naltrexone implants produce significant social behavioral effects within 1 day, and are effective at attenuating the conditioned place preference produced by cocaine. PMID- 9972852 TI - Lorazepam attenuates the behavioral effects of dizocilpine. AB - To characterize the potential interaction between the excitatory and inhibitory neurotransmitter systems, the effects of dizocilpine, CPP, and lorazepam on open field behavior and pentylenetetrazol-induced seizures were evaluated in mice. Dizocilpine (0.01-0.1 mg/kg), CPP (1-10 mg/kg), or vehicle was administered intraperitoneally 15 min prior to lorazepam (0.2-2 mg/kg) or vehicle. Behavioral monitoring began 25 min after the lorazepam injection. Upon completion of testing, unrestrained mice were infused intravenously with pentylenetetrazole until the onset of a full tonic-clonic seizure. The highest dose of dizocilpine by itself significantly increased the average distance traveled, the number of rears, and the number of stereotypies during the test period. Lorazepam alone dose dependently decreased activity on all behavioral parameters. Lorazepam also completely antagonized the hyperactivity produced by dizocilpine when the two compounds were coadministered. This antagonism is most likely due to an interaction in the regulation of dopaminergic tone which underlies motor activity. Lorazepam exerted a dose-dependent anticonvulsant effect. Dizocilpine alone had no effect on seizure induction and did not potentiate the anticonvulsive effect of lorazepam when coadministered with lorazepam. CPP reduced the number of rears and the number of stereotypies during the test period. CPP did not alter the pentylenetetrazol-induced seizure threshold and did not influence the anticonvulsant effect of lorazepam. PMID- 9972854 TI - Possible involvement of a sigma receptor subtype in the neck dystonia in rats. AB - To clarify which subtype of sigma receptors is involved in the sigma receptor mediated neck dystonia in rats, we examined whether 1-(3,4-dimethoxyphenethyl)-4 (3-phenylpropyl)piperazine dihydrochloride (SA4503), a selective sigma1 receptor agonist, and 1,3-di-(2-tolyl)guanidine (DTG), a sigma1 and sigma2 receptor agonist, induce neck dystonia in rats. Microinjection of SA4503 into the red nucleus of rat brain scarcely produced neck dystonia at the concentration of 10 nmol/0.5 microl. On the contrary, DTG produced significant dystonia at a concentrations of more than 5 nmol/0.5 microl. These results indicate that the sigma2 receptor subtype, but not sigma1 receptor subtype, may play an important role in the sigma receptor-mediated neck dystonia in rats. PMID- 9972853 TI - Parallel recovery of MK-801-induced spatial learning impairment and neuronal injury in male mice. AB - The relationship between spatial learning impairment and reversible neuronal injury in the posterior cingulate/retrosplenial (PC/RS) cortex induced by MK-801 in male mice was studied using a four-corner holeboard task. Mice were dosed with 1 mg/kg MK-801 and tested on acquisition of a new "baited" hole at 5 or 12 h posttreatment. Acquisition in drugged mice was impaired at 5 h, but not at 12 h posttreatment. Their retention performances were unaffected 24 h after either the 5 or 12 h posttreatment acquisition sessions. MK-801 (1 mg/kg) was found to induce locomotor hyperactivity and some sensorimotor impairment at 5 h posttreatment. which could have contributed to the acquisition deficit. However, nonassociative effects of the drug were not prominent because this same dose did not impair holeboard performance at 5 h posttreatment when the task was well learned. Histologic experiments showed that many injured neurons (containing cytoplasmic vacuoles) were present in the PC/RS cortex at 5 h posttreatment but the reaction was essentially reversed at 12 h posttreatment. The results suggest that the acquisition impairment and neuronal injury induced by MK-801 evolve and recover in parallel according to a similar time schedule. PMID- 9972855 TI - Presentation of an ethanol-paired stimulus complex alters response patterns during extinction. AB - It has been hypothesized that environmental stimuli previously paired with ethanol consumption play a role in excessive ethanol intake. This study examined the ability of orally self-administered ethanol to establish a tone-light stimulus complex as a conditioned reinforcer (CSR). Male Long-Evans rats were trained to orally self-administer 10% ethanol (10E) using the sucrose substitution procedure. During training, a tone-light stimulus complex was paired with ethanol presentation in a stimulus complex paired (SC-paired) group but not in a control group. Responding during extinction in the presence and absence of the stimulus complex was then examined. Following the initiation of ethanol self administration, 10E maintained greater responding in the SC-paired group compared to the control group. When the stimulus complex was presented contingent on responding during extinction, the rate of extinction was slightly attenuated in the SC-paired group but not in the control group. The altered rate of extinction in the SC-paired group was characterized by: 1) a slight decrease in total session responding over successive days of extinction and 2) a transient attenuation of extinction burst response rate during the first extinction session. These data suggest the stimulus complex could function as a weak CS(R), but overall its ability to maintain lever pressing was minimal. PMID- 9972856 TI - The effects of neonatal cocaine exposure on a play-rewarded spatial discrimination task in juvenile rats. AB - This study examined the effects of neonatal cocaine exposure on the rewarding properties of play in a modified T-maze. Animals were artificially reared from postnatal day (PND) 4-9 with drug concentrated in four daily feeds. There were four treatment groups, 40 mg/kg/day cocaine, 20 mg/kg/day cocaine, an artificially reared control and a surgery control. From PND 38-42, subjects were tested with a food reward (EXP 1) or a play reward (EXP 2). No deficits in learning were seen when the reward was food. The 20 mg/kg/day cocaine group, however, showed impaired learning and altered play behavior when the reward was access to a play partner. Neonatal cocaine exposure thus appears to differentially affect learning based on the type of reward presented. PMID- 9972857 TI - Effects of neonatal naltrindole treatment on antinociceptive and behavioral responses to mu and kappa agonists in rats. AB - The effects of a daily injection of the delta selective opioid antagonist naltrindole (1 mg/kg), from birth to postnatal day 19, on antinociceptive and behavioral responses to the mu selective agonist alfentanil (65 microg/kg) and the kappa selective agonist CI-977 (50 microg/kg) in 20-day-old male rats were investigated. Antinociception was assessed using the tail immersion test and behavioral testing was performed by employing an open field. The functional blockade of the delta receptor by naltrindole blocked the antinociceptive response to alfentanil but did not affect the antinociception induced by CI-977. The effects of alfentanil (increased exploration) and CI-977 (a marked hypoactivity) in the open field were not modified by neonatal naltrindole treatment. The results suggest a functional interaction between delta and mu receptors in the postnatal period but not between delta and kappa receptors. The data also suggest differences in the delta and mu receptors interacting in the modulation of antinociception and those involved in behavioral responses in the open field. PMID- 9972858 TI - The type IV phosphodiesterase inhibitors, Ro 20-1724 and rolipram, block the initiation of cocaine self-administration. AB - The hypothesis that the selective activation of cyclic AMP (cAMP) signal transduction pathways will suppress the initiation of cocaine self-administration was examined in this investigation. To test this hypothesis, the effects of the administration of the cAMP-specific (type IV) phosphodiesterase inhibitors, rolipram and Ro 20-1724, on cocaine self-administration were determined. The effects of Ro 20-1724 treatment on operant responding for food also were examined. Both cocaine and food were delivered following a fixed-ratio 5 schedule. A significant increase in the latency for the delivery of the first cocaine infusion and a reduction in the number of infusions obtained per session were produced by treatment with either rolipram or Ro 20-1724. Similar effects on responding for food were seen with Ro 20-1724 administration. Responding after drug-induced delays tended to be at control levels. These results suggest that cAMP-specific phosphodiesterase inhibitors may inhibit the initiation of operant responding for either cocaine or food. However, the extent to which these actions involve specific effects on central motivational systems as opposed to other mechanisms remains to be determined. PMID- 9972859 TI - The effects of diazepam and zolpidem on cocaine- and amphetamine-induced place preference. AB - Drugs such as benzodiazepines, which enhance the effects of inhibitory neurotransmitter gamma-amino butyric acid (GABA), are known to modulate the mesocorticolimbic dopaminergic system, which is considered to mediate the rewarding effects of psychostimulants. The effects of diazepam, a benzodiazepine that binds unspecifically to omega 1- (omega1-) and omega2-receptors, and zolpidem, a nonbenzodiazepine drug that binds preferentially to omega1-receptors, on cocaine- and amphetamine-induced place preference were evaluated in Wistar rats. In tests using the counterbalanced method, neither diazepam (0.2, 1, and 5 mg/kg) nor zolpidem (2.5, 5, and 10 mg/kg) alone induced place preference or place aversion. Diazepam pretreatment prevented both cocaine- and amphetamine induced (15 and 9 mg/kg, respectively) place preference; however, at doses that were earlier shown to cause sedation and amnesia, zolpidem failed to prevent either cocaine- or amphetamine-induced place preference. These results suggest that diazepam interferes with the rewarding properties of the psychostimulants, whereas zolpidem is less effective in this respect, possibly due to differential distribution of omega1- and omega2-receptors in the brain. PMID- 9972860 TI - Blockade of smoking satisfaction using the peripheral nicotinic antagonist trimethaphan. AB - The present study was conducted to investigate the role of peripheral nicotinic receptors in mediating the rewarding effects of cigarette smoking. Twelve cigarette smokers rated cigarettes after intravenous infusion of the short-acting peripheral nicotinic receptor antagonist trimethaphan and after placebo (saline) infusions. Subjects were blinded to the infusion and cigarette conditions. Cigarette conditions included subjects' usual brand of cigarette, denicotinized tobacco cigarettes, and nicotine-injected cigarettes that had a tar delivery equal to that of the denicotinized cigarettes but with an enhanced nicotine delivery equal to that of subjects' usual brands. The latter cigarettes were rated as extremely harsh due to the high nicotine/tar ratio. Trimethaphan significantly attenuated the airway sensations associated with nicotine, and eliminated the difference in smoking satisfaction between the usual brand of cigarette and the other two cigarettes. These findings suggest that nicotinic receptors on peripheral nerve endings in the respiratory tract modulate smoking satisfaction and may be important in the maintenance of cigarette addiction. PMID- 9972861 TI - Differential behavioral effects of TFF peptides: injections of synthetic TFF3 into the rat amygdala. AB - TFF peptides (formerly named P-domain peptides or trefoil factors) are also released from the brain as well as being secreted typically by mucin producing cells. The amygdala, besides the hypothalamus, represents a defined neuronal locality of TFF3 synthesis. In a passive avoidance test synthetic TFF3/monomer or 0.9% sodium chloride (control) was injected bilaterally into the basolateral nucleus of the amygdala of male rats either immediately (consolidation test) or 23 h after a footshock (retrieval test). Application of a low TFF3 dose (2 x 6 pg) decreased avoidance latency in a time dependent manner. In contrast, a high dose (2 x 60 pg) increased avoidance latency. Maximal effects of TFF3 were observed about 24 h after the injection. This bidirectional effect was also observed using the elevated plus-maze test. The locomotor activity on the open arms was significantly increased 24 h after a low dose injection of TFF3 into the amygdala. In contrast, a high-dose injection significantly decreased the activity on the open arms. The results of both tests can be explained by an anxiolytic effect at a low dose and an anxiogenic effect at a high dose of synthetic TFF3/monomer. PMID- 9972862 TI - Influence of sex and female hormones on nicotine-induced changes in locomotor activity in rats. AB - The acute and chronic effects of nicotine (0.4 mg/kg s.c.) on locomotor activity in photocell cages have been compared in male, female, and ovariectomized hooded rats. In Experiment 1, female rats displayed higher locomotion than males (n = 12); acutely, nicotine-reduced locomotion, and this effect was slightly larger in females than males. Daily administration of nicotine for 21 days produced a similar, gradual increase in activity in both sexes. Tests then confirmed greater activity in females than males and as a function of previous chronic exposure to nicotine (n = 6); there was an activating effect of nicotine challenge but no interaction of nicotine effects with sex. In Experiment 2, ovariectomized rats were primed with 17-beta-estradiol (50 microg/kg s.c.) and progesterone (2.5 mg/kg s.c.) or vehicle only. Acute administration of nicotine reduced activity in both groups similarly (n = 12). After nicotine daily for 21 days, there was increased activity as a function of both chronic nicotine and hormonal priming, and challenge with nicotine increased activity (n = 6). The effects of these challenges with nicotine were also slightly greater, as a function of previous nicotine exposure and priming. As a whole, these experiments showed robust effects of acute and chronic nicotine administration, sex, and hormonal priming; neither sex nor gonadal hormones had marked influences on changes in locomotor activity produced by nicotine. PMID- 9972863 TI - Nitrous oxide-induced hypothermia in the rat: acute and chronic tolerance. AB - Although inhalation of nitrous oxide (N2O) causes hypothermia in rats, there is a paucity of information as to whether tolerance develops to this effect. The purpose of this study was to determine whether tolerance to N2O hypothermia develops within a single administration as well as over repeated administrations. Temperature was measured telemetrically by implanting intraperitoneal thermal sensors/transmitters in male Long-Evans rats. Experimental rats received an initial 2-h exposure to 60% N2O and became hypothermic relative to controls breathing placebo gas. Only a few rats demonstrated evidence of acute tolerance over the 120 min. Over the next 10 days, the experimental rats received five additional 30-min exposures to 60% N2O and five 30-min exposures to placebo while the control rats received only placebo gas exposures. Chronic tolerance developed to N2O hypothermia over these repeated administrations. A test for Pavlovian drug conditioning found no evidence that conditioned temperature effects contributed to chronic tolerance development. In a second experiment, naive rats were given a 380-min exposure to 60% N2O and a 380-min exposure to placebo gas in a counterbalanced order. Acute tolerance did develop to N2O hypothermia, with the recovery of temperature beginning after a mean of 141 min of gas administration. Hence, both acute and chronic tolerance develop to N2O's hypothermic effects in rats. PMID- 9972864 TI - Plasma and red blood cell fatty acids in peroxisomal disorders. AB - The demonstration of abnormal levels of fatty acids or plasmalogens in plasma or red blood cells is key to the diagnosis of peroxisomal disorders. We report the levels of 62 fatty acids and plasmalogens in patients with X-linked adrenoleukodystrophy (X-ALD), Zellweger syndrome (ZS), neonatal adrenoleukodystrophy (NALD), and infantile Refsum disease (IRD), both at baseline and after dietary interventions. "Lorenzo's Oil" therapy in X-ALD normalizes the levels of saturated very long chain fatty acids in plasma, but leads to reduced levels of omega 6 and other omega 3 fatty acids, and requires monitoring and appropriate dietary supplements. Patients with ZS, NALD and IRD have reduced levels of docosahexaenoic acid (DHA) and arachidonic acid (AA) which can be normalized by the oral administration of microencapsulated DHA and AA. PMID- 9972865 TI - Sphingosylphosphorylcholine in Niemann-Pick disease brain: accumulation in type A but not in type B. AB - A study of brain lipids in patients with the sphingomyelinase-deficient types of Niemann-Pick disease demonstrated that abnormal accumulation of sphingomyelin occurs only in the brain of neuronopathic type A patients but not in the non neuronopathic type B. Additional lipid abnormalities were present in the type A brain. In contrast, the brain lipid profile was normal in type B patients. Since lysosphingolipids have been implicated in the biochemical pathogenesis of other genetic lysosomal sphingolipidoses, the occurrence of sphingosylphosphorylcholine (lysosphingomyelin) was specifically investigated in brain and extraneural tissues, using an HPLC method with fluorescent detection of orthophtalaldehyde derivatives. Levels close to or below the limit of detection (10 pmol/mg tissue protein) were observed in normal and pathological controls. A striking accumulation was observed in brain of two Niemann-Pick type A patients (830 and 430 pmol/mg protein in 27-and 16-month-old children with severe and milder neurological course, respectively), which was not present at the fetal stage of the disease. No significant increase was found in brain tissue from a 3.5 year old type B patient. In liver and spleen, abnormally high sphingosylphosphorylcholine levels were observed in both types of the disease, with indication of a progressive increase during development. This study establishes the integrity of brain tissue in Niemann-Pick disease type B and suggests that the lysocompound sphingosylphosphorylcholine could play a role in the pathophysiology of brain dysfunction in the neuronopathic type A. PMID- 9972866 TI - Clinical and molecular characteristics of Japanese Gaucher disease. AB - Clinical signs and symptoms of Gaucher disease are more severe in Japanese than in Jewish and other non-Japanese patients. A higher percentage of bone crises and splenectomy was demonstrated by Japanese patients, and there were five fatalities among patients with type 1 Gaucher disease. Additionally, neonatal Gaucher disease, clinically characterized by hydrops foetalis, was observed. Japanese patients with type 2 and type 3 disease also demonstrate clinical heterogeneity. About 100 alleles of patients with Japanese Gaucher disease were examined for genotype determination with the PCR and SSCP methods. About 18 different mutations, including several novel mutations in Japanese patients, were identified. The most common mutations in Japanese patients were 1448C(L444P), accounting for 41 (41%) of alleles. The second most prevalent mutation was 754A(F2131), accounting for 14 (14%) of alleles. Other alleles identified included the 1324C, IVS2 and other mutations. Unidentified alleles comprised 16% of the total number of alleles studied. To date, neither the 1226G (N370S) nor the 84GG mutation has been identified in the Japanese population, although these mutations account for about 70% and 10% of the mutations in Jewish and other non Japanese populations, respectively. The phenotype-genotype correlation in Japanese patients is more complex compared with that of the Jewish population. In Japanese patients, the 1448C mutation, in either heteroallelic or homoallelic forms, exhibits both neurological and non-neurological phenotypes. Japanese patients with the 754A mutation also exhibit both neuronopathic and non neuronopathic disease. On the other hand, patients with the D409H mutation show only type 3 neurological disease, and those with the 1447-1466 del 20 ins TG mutation have the severe, neonatal neurological form of Gaucher disease. The 1503T allele was present only in patients with type 1 non-neurological disease. However, since this correlation was observed only in young patients, we do not as yet know the final phenotypic outcome of this mutation. Probably, Japanese patients with Gaucher disease have few mutations that exhibit non-neurological signs and symptoms. PMID- 9972867 TI - Cell reactions following acute brain injury: a review. AB - The proliferative behavior of glia following a cerebral stab wound in adult rats is reviewed. Proliferation was determined by both PCNA and [3H]thymidine labeling. Microglia were the first cells to divide and constituted the bulk of dividing cells. Both ramified and ameboid microglia divided. A smaller number of astrocytes entered the cell cycle a day later and were shown to derive from differentiated reactive cells. No differentiated oligodendroglia were labeled by thymidine, although a small number of dividing immature oligodendroglia could be detected in cultures of cells labeled in vivo. Recent studies of the properties of oligodendroglial precursors in brain repair mechanisms are discussed. The results so far support our conclusion that differentiated oligodendrocytes do not divide. PMID- 9972868 TI - GM1 inhibits amyloid beta-protein-induced cytokine release. AB - The ganglioside GM1 is known to play a pivotal role in neuronal survival and/or regeneration. Recently it has been shown that GM1 binds tightly with membrane bound amyloid beta protein (A beta) and prevents its conversion from a helical to a beta-sheet structure. To examine the potential physiological consequences of this binding, we studied the effect of GM1 on A beta-stimulated release of proinflammatory cytokines, such as interleukin (IL)-1beta, IL-6 and TNF-alpha, using the human monocytic cell line, THP-1, as a model system. Treatment of THP-1 cells with A beta 1-40 or A beta 25-35 resulted in an increased cytokine release from these cells. However, treatment of A beta-activated THP-1 cells with GM1 and several other complex gangliosides, but not hematosides and neutral glycosphingolipids such as asialo-GM1 (GA1), lactosylceramide, and globoside, significantly decreased the cytokine release. In contrast, this effect was not observed for lipopolysaccharide (LPS)-activated and thrombin-activated THP-1 cells, indicating that the ganglioside effect is specific for A beta-induced cytokine release. A direct interaction between GM1 and A beta was demonstrated using the surface plasmon resonance technique. We found that GM1 ganglioside exhibited higher affinity for A beta 1-40 than GA1, suggesting that the sialic acid moiety of GM1 is necessary for its interaction with A beta. We conclude that the inhibitory effect of GM1 on A beta-induced cytokine release may reflect pre existing abnormalities in membrane transport at the stage of amyloid formation and that GM1 may induce conformational changes in A beta, resulting in diminished fibrillogenesis and prevention of the inflammatory response of neuronal cells in Alzheimer's disease. PMID- 9972869 TI - Prolongation of life in an experimental model of aging in Drosophila melanogaster. AB - (R)-Deprenyl, the archetypical monoamine oxidase-B inhibitor, has been shown to increase life-span in a number of species. Although many theories for this effect have been suggested, for example, an increase in superoxide dismutase (SOD) activity, the mechanism of action has yet to be elucidated. To investigate this phenomenon, we have examined the effects of (R)-deprenyl, and some aliphatic propargylamines, in an experimental aging model in Drosophila melanogaster. Both wild-type Oregon-R type flies, as well as a SOD knock-out mutant strain were used. Flies obtained from a series of paired mates were divided equally among treatment groups. In all studies, flies were treated for the duration of life following adult emergence. The aging model consists of substitution of sucrose with galactose in the regular food media of the flies. Initial experiments confirmed that such a substitution resulted in a significant (p < 0.01, Breslow test) reduction in mean and maximal life-span of flies, an effect not due to nutrient deprivation. Inclusion of (R)-deprenyl and the aliphatic propargylamines in the media, at average daily doses in the range 0.5-1 ng/fly/day, led to a significant increase in mean and maximal life-span of galactose-treated, but not control flies. This effect was seen in both wild-type and mutant flies. PMID- 9972870 TI - Transferrin is an essential factor for myelination. AB - It has been established that oligodendrocytes, the myelin forming cells, participate in iron homeostasis through the synthesis and secretion of transferrin. Here we investigated whether a correlation exists between myelination, the commonly studied function of oligodendrocytes, and that of transferrin synthesis and secretion. We used a proteolipid protein mutant, the myelin deficient rat, whose condition is characterized by severe hypomyelination. We compared the ontogenic profile for transferrin gene expression in mutants with that of unaffected rat pups through northern blot analysis and in situ hybridization. Surprisingly, transferrin synthesis was null in mutant oligodendrocytes. Next, we demonstrated that a single apo-transferrin intraparenchymal injection administered to P5 rat pups enabled mutant oligodendrocytes to synthesize myelin basic protein and to myelinate axons, indicating that transferrin effects mutant oligodendrocyte maturation regardless of its source. Thus, transferrin availability is essential for oligodendrocyte maturation and function, and oligodendrocytes are most vulnerable to transferrin deficiency during the premyelinating stage. PMID- 9972871 TI - The phosphoinositide signaling cycle in myelin requires cooperative interaction with the axon. AB - Previous studies on the origin of myelin phosphoinositides involved in signaling mechanisms indicated axon to myelin transfer of phosphatidylinositol followed by myelin-localized incorporation of axon-derived phosphate groups into phosphatidylinositol 4-monophosphate and phosphatidylinositol 4,5-bisphosphate. This is in agreement with other studies showing the presence of phosphorylating activity in myelin that converts phosphatidylinositol into the mono-and diphospho derivatives. It was also found that the second messenger, inositol 1,4,5 trisphosphate, is hydrolyzed to inositol 1,4-bisphosphate by a myelin-localized enzyme. The present study was undertaken to determine the locus of the remaining reactions leading to formation of free inositol and completion of the cycle by resynthesis of phosphatidylinositol. The latter reaction was found to occur preferentially in isolated axons, and to a limited extent if at all in myelin. On the other hand, hydrolytic reactions which sequentially convert inositol 1,4,5 trisphosphate to inositol 1,4-bisphosphate, inositol 1-phosphate, and free inositol were found to occur more prominently in myelin. Thus, restoration of phosphoinositides following signal-induced breakdown of PIP2 in myelin is seen as requiring metabolic interplay between myelin and axon. PMID- 9972872 TI - Myelin basic protein and myelin basic protein peptides induce the proliferation of Schwann cells via ganglioside GM1 and the FGF receptor. AB - Myelin basic protein (MBP) and two peptides derived from MBP (MBP(1-44) and MBP(152-167)) stimulated Schwann cell (SC) proliferation in a cAMP-mediated process. The two mitogenic regions of MBP did not compete with one another for binding to SC suggesting a distinctive SC receptor for each mitogenic peptide. Neutralizing antibodies to the fibroblast growth factor receptor blocked the mitogenic effect of the myelin-related SC mitogen found in the supernatant of myelin-fed macrophages. The binding of 125I-MBP to Schwann cells was specifically inhibited by basic fibroblast growth factor (bFGF) and conversely the binding of 125I-bFGF was competitively inhibited by MBP. These data suggested that the mitogenic effect of one MBP peptide was mediated by a bFGF receptor. The binding of MBP to ganglioside GM1 and the ability of MBP peptides containing homology to the B subunit of cholera toxin (which binds ganglioside GM1) to compete for the binding of a mitogenic peptide (MBP(1-44)) to SC, identified ganglioside GM1 as a second SC receptor. Based on these results, we conclude that MBP(1-44) and MBP(152-167) associate with ganglioside GM1 and the bFGF receptor respectively to stimulate SC mitosis. PMID- 9972873 TI - Phagocytosis of myelin in demyelinative disease: a review. AB - In the cell-mediated demyelinating diseases such as experimental allergic encephalomyelitis and multiple sclerosis, as well as their peripheral nerve counterparts, the phagocytic cells are the agent of myelin destruction. Both resident microglia and peripheral macrophages invading the nervous system have been shown to phagocytize myelin, although microglia appear to be more active, especially at early stages of disease. Several different receptors on these cells have been implicated as myelin receptors, with the Fc- and complement receptors receiving the most attention. Other receptors, especially the macrophage scavenger receptor with its broad specificity deserves further exploration, especially in view of its affinity for phosphatidylserine, which becomes externalized with membrane disruption. Evidence is shown for cytokine regulation of phagocytic activity in both macrophages and microglia. Further investigation of the pathways of cytokine action on myelin phagocytosis through signal transduction molecules will be important for a further understanding of the events leading to myelin destruction in demyelinating diseases. PMID- 9972874 TI - Fatty acid composition of myelin proteolipid protein during vertebrate evolution. AB - The hydrophobic myelin proteolipid protein (PLP) contains covalently bound long chain fatty acids which are attached to intracellular cysteine residues via thioester linkages. To gain insight into the role of acylation in the structure and function of myelin PLP, the amount and pattern of acyl groups attached to the protein during vertebrate evolution was determined. PLP isolated from brain myelin of amphibians, reptiles, birds and several mammals was subjected to alkaline methanolysis and the released methyl esters were analyzed by gas-liquid chromatography. In all species studied, PLP contained approximately the same amount of covalently bound fatty acids (3% w/w), and palmitic, palmitoleic, oleic and stearic acids were always the major acyl groups. Although the relative proportions of these fatty acids changed during evolution, the changes did not necessarily follow the variations in the acyl chain composition of the myelin free fatty acid pool, suggesting fatty acid specificity. The phylogenetic conservation of acylation suggests that this post-translational modification is critical for PLP function. PMID- 9972875 TI - Expression of the GM1-species, [NeuN]-GM1, in a case of human glioma. AB - Altered glycosylation is a common feature in tumors of various kind and particular interest has been focused on the expression of tumor-associated gangliosides. We have previously identified some human glioma-associated gangliosides and in this study yet another, not previously described, ganglioside has been isolated. The ganglioside was prepared from human glioma tissue taken at autopsy. The new ganglioside bound cholera-toxin B-subunit and its structure was confirmed by fast atom bombardment-mass spectrometry to be NeuN-GM1 (II3NeuNH2 GgOse4Cer). In the dissected tumor specimen, the concentration of NeuN-GM1 was 0.1 micromol/g wet weight and accounted for approximately 20% of the monosialoganglioside fraction. Normal human brain tissue specimens (n = 10) did not contain detectable (>0.5 nmol/g wet weight of tissue) amounts of NeuN-GM1, indicating that this ganglioside might be associated with human glioma. However, none of the 17 other tumour specimens reveal any detectable amounts of this ganglioside. In conclusion, NeuN GM1 is a glioma-associated ganglioside but its exceptional expression limits its relevance as a molecule involved in general tumor biology. PMID- 9972876 TI - GM2 promotes ciliary neurotrophic factor-dependent rescue of immortalized motor neuron-like cell (NSC-34). AB - We have examined whether ciliary neurotrophic factor (CNTF) can alter serum-free cell survival of immortalized motor neuron-like cells, which were established by fusing mouse neuroblastoma N18TG2 with mouse motor neurons. One of the cell lines, NSC-34 exhibited cell survival in the presence of CNTF. NSC-34 preserves the most characteristics of motor neurons, such as the formation of neuromuscular junctions on co-cultured myotube. GM2 ganglioside is characteristic of motor neurons, and expressed highly in NSC-34. When NSC-34 was cultured with exogenous GM2 ganglioside and CNTF, GM2 facilitated the cell survival effect of CNTF. In the addition, beta 1,4 N-acetylgalactosaminyltransferase (GM2 synthase) activity was enhanced up to 3.9-fold by culture in the presence of CNTF. GM2 might be a functional modulator of CNTF in motor neurons. It might be presented to cell surface by its enzyme activation, and become a signal of early stage, when CNTF rescues motor neurons. PMID- 9972877 TI - Transduction of cultured oligodendrocytes from normal and twitcher mice by a retroviral vector containing human galactocerebrosidase (GALC) cDNA. AB - Krabbe disease or globoid cell leukodystropy is a lysosomal disorder caused by a deficiency of galactocerebrosidase (GALC) activity. This results in defects in myelin that lead to severe symptoms and early death in most human patients and animals with this disease. With the cloning of the GALC gene and the availability of the mouse model, called twitcher, it was important to evaluate the effects of providing GALC via a retroviral vector to oligodendrocytes in culture. After differentiation, the untransduced cells from normal mice extended highly branched processes while those from the twitcher mice did not. Oligodendrocytes in culture can be readily transduced to produce much higher than normal levels of GALC activity. Transduced normal and twitcher cells formed clusters when plated at high density. Transduction of twitcher oligodendrocytes plated at lower density, followed by differentiation, resulted in some cells having a completely normal appearance with highly branched processes. Other cells showed retraction and fragmentation. Perhaps over expression of GALC activity may be detrimental to oligodendrocytes. These studies demonstrate that the phenotype of twitcher oligodendrocytes can be corrected by providing GALC via gene transfer, and this could lead the way to future studies to treat this disease. PMID- 9972878 TI - Recombinant GM2-activator protein stimulates in vivo degradation of GA2 in GM2 gangliosidosis AB variant fibroblasts but exhibits no detectable binding of GA2 in an in vitro assay. AB - The interaction between glycosphingolipids and recombinant human GM2-activator was studied in a microwell binding assay. A-series gangliosides like GM3, GM2 and GM1 were strongly bound by the recombinant human GM2 activator. A weak binding was observed to GD1b and sulfatide, while neutral glycolipids were not bound. Optimal binding occurred at pH 4.2 and was inhibited by increasing concentrations of citrate buffer and NaCl. In contrast with these in vitro results the recombinant human GM2-activator is able to restore the degradation of GA2 in fibroblasts from patients with the AB variant of GM2 gangliosidosis in vivo. PMID- 9972879 TI - Delivery, distribution, and neuronal uptake of exogenous mannose-terminal glucocerebrosidase in the intact rat brain. AB - Gaucher disease is caused by insufficient activity of the enzyme glucocerebrosidase. Great benefit has been obtained through enzyme replacement therapy for patients with type 1 (non-neuronopathic) Gaucher disease. In contrast, inconsistent effects of enzyme therapy have been observed in patients with type 3 (chronic neuronopathic) Gaucher disease, and no benefit on the lethal course of the disease occurs in patients with Type 2 (acute neuronopathic) Gaucher disease. We examined the use of convection-enhanced delivery to augment the delivery and distribution of exogenous glucocerebrosidase (m.w. 63,000) to the brain by infusing it under slight hydrostatic pressure into the striatal region of rats. The enzyme was comparatively stable under these conditions. It was distributed from the site of injection toward the cerebral cortex where it became primarily localized in neurons. These findings provide considerable incentive for the exploration of intracerebral microinfusion of enzyme to the brain of patients with metabolic storage disorders involving the CNS. PMID- 9972880 TI - Saposins and their interaction with lipids. AB - The lysosomal degradation of several sphingolipids requires the presence of four small glycoproteins called saposins, generated by proteolytic processing of a common precursor, prosaposin. Saposins share several structural properties, including six similarly located cysteines forming three disulfide bridges with the same cysteine pairings. Recently it has been noted that also other proteins have the same polypeptide motif characterized by the similar location of six cysteines. These saposin-like (SAPLIP) proteins are surfactant protein B (SP-B), 'Entamoeba histolytica' pore-forming peptide, NK-lysin, acid sphingomyelinase and acyloxyacyl hydrolase. The structural homology and the conserved disulfide bridges suggest for all SAPLIPs a common fold, called 'saposin fold'. Up to now a precise fold, comprising five alpha-helices, has been established only for NK lysin. Despite their similar structure each saposin promotes the degradation of specific sphingolipids in lysosomes, e.g. Sap B that of sulfatides and Sap C that of glucosylceramides. The different activities of the saposins must reside within the module of the alpha-helices and/or in additional specific regions of the molecule. It has been reported that saposins bind to lysosomal hydrolases and to several sphingolipids. Their structural and functional properties have been extensively reviewed and hypotheses regarding their molecular mechanisms of action have been proposed. Recent work of our group has evidenced a novel property of saposins: some of them undergo an acid-induced change in hydrophobicity that triggers their binding to phospholipid membranes. In this article we shortly review recent findings on the structure of saposins and on their interactions with lipids, with special attention to interactions with phospholipids. These findings offer a new approach for understanding the physiological role of saposins in lysosomes. PMID- 9972881 TI - Neurotransmitter release from the medial hyperstriatum ventrale of the chick forebrain accompanying filial imprinting behavior, measured by in vivo microdialysis. AB - The imprinting behavior of chicks was quantified as a preference score (correct response ratio) achieved in a running wheel apparatus. A total of 249 chicks were exposed to an imprinting stimulus and tested for stimulus-approaching behavior. The chicks were then classified as good learners (imprinted), poor learners (non imprinted) and a gray-zone group, those were 46%, 31% and 23% of the total chicks respectively. Using the classified chicks, the acetylcholine (ACh) and glutamate releases from the medial hyperstriatum ventrale (MHV) of the chick forebrains were determined by in vivo microdialysis. The non-imprinted chicks were used as yoked controls. Increases of ACh and glutamate released were observed in the imprinted chicks during exposure to the imprinting stimulus, whereas there were no changes in the release of these neurotransmitters in the non-imprinted chicks during the imprinting exposure. These results might be indicated that cholinergic and glutamatergic synapses which are newly formed as functioning synapses with imprinting stimulus in the MHV are involved in the performance of imprinting behavior. PMID- 9972882 TI - Energetics of functional activation in neural tissues. AB - Glucose utilization (ICMRglc) increases linearly with spike frequency in neuropil but not perikarya of functionally activated neural tissues. Electrical stimulation, increased extracellular [K+] ([K+]o), or opening of Na+ channels with veratridine stimulates ICMRglc in neural tissues; these increases are blocked by ouabain, an inhibitor of Na+,K+-ATPase. Stimulating Na+,K+-ATPase activity to restore ionic gradients degraded by enhanced spike activity appears to trigger these increases in ICMRglc. Cultured neurons behave similarly. Astrocytic processes that envelop synapses in neuropil probably contribute to the increased ICMRglc. ICMRglc in cultured astroglia is unaffected by elevated [K+]o but is stimulated by increased intracellular [Na+] ([Na+]i), and this stimulation is blocked by ouabain or tetrodotoxin. L-Glutamate also stimulates ICMRglc in astroglia. This effect is unaffected by inhibitors of NMDA or non-NMDA receptors, blocked by ouabain, and absent in Na+-free medium; it appears to be mediated by increased [Na+]i due to combined uptake of Na+ with glutamate via Na+/glutamate co-transporters. PMID- 9972883 TI - Oligodendroglial response to the immune cytokine interferon gamma. AB - In the human demyelinating disorder multiple sclerosis, and its animal model experimental allergic encephalomyelitis, there is a breakdown of the blood-brain barrier and an infiltration of immune cells into the CNS. Infiltrating T lymphocytes and macrophages are believed to be key mediators of the disease process. Considerable circumstantial and experimental evidence has suggested that the pleiotropic cytokine interferon gamma (IFN-gamma), which is exclusively expressed by T cells and natural killer cells, is a deleterious component of the immune response in these disorders. When experimentally introduced into the CNS IFN-gamma promotes many of the pathological changes that occur in immune-mediated demyelinating disorders. In vitro, this cytokine elicits a number of effects on oligodendrocytes, including cell death. The harmful actions of IFN-gamma on CNS myelin are likely mediated through direct effects on the myelinating cells, as well as through the activation of macrophages and microglia. In this review we summarize relevant studies concerning the action of IFN-gamma in demyelinating disorders and discuss possible mechanisms for the observed effects. PMID- 9972884 TI - Suppression of glial tumor growth by expression of glial fibrillary acidic protein. AB - We examined the effect of expression of glial fibrillary acidic protein (GFAP) on the tumor growth of astrocytoma in vivo. When rat astrocytoma C6 cells were injected subcutaneously in athymic mice, the cells produced tumors that grew rapidly. The tumor growth of C6 cells transfected with GFAP cDNA was significantly reduced compared to that of control NeoC6 cells transfected only with the neomycin resistant gene. After implantation of C6 cells transfected with mutated GFAP cDNA at the phosphorylation sites, the tumor growth was suppressed similar to that of the wild GFAP transfectants. To determine whether the cell growth suppression by GFAP is specific for astroglial cells, we assessed the effect of GFAP on the cell growth of an L cell of fibroblast origin in vitro. By GFAP cDNA transfection, L cells showed morphological changes, but the cell growth was not reduced. These results suggest that GFAP is a critical regulator of the tumor growth of astrocytoma. PMID- 9972885 TI - Carotid endarterectomy: changing practice patterns. AB - BACKGROUND: Cost-effective carotid endarterectomy implies a good outcome; low morbidity, a short hospital stay and selective use of non-invasive preoperative diagnostic tests done alone. METHODS: A solo surgeon's clinical experience with two hundred and eighteen consecutive operations, over seven years, at two Community Hospitals in Northern Virginia. RESULTS: There were three perioperative strokes, of which one resulted in death, for a mortality rate of 0.45%, and a stroke rate of 1.4%. The majority of the operations in the past two years were done on the basis of Duplex ultrasonography and magnetic resonance angiography, but without invasive angiography. General anesthesia, routine use of shunt and use of autogenous vein patch in almost every case was employed. Patients were selectively observed in the Intensive Care Unit postoperatively. Forty eight percent of the series and 75% of the most recent 121 patients operated on in 1995 and 1996 were discharged on the first postoperative day without any need for re admission to the hospital. CONCLUSIONS: Carotid endarterectomy can be performed with a short hospital stay and an extremely low morbidity and mortality. Carotid endarterectomy is a highly effective surgical procedure both from the medical and economy stand-points. PMID- 9972886 TI - Selective targeting and photodynamic destruction of intimal hyperplasia by scavenger-receptor mediated protein-chlorin e6 conjugates. AB - BACKGROUND: Photosensitizers, such as Photofrin II or Chloroaluminum-sulfonated phthalocyanine accumulate at sites of arterial injury. We have exploited this property to develop a model of photodynamic therapy (PDT) for intimal hyperplasia. The fluorescent probe [maleylated-bovine serum albumin (mal-BSA) conjugated with Texas-red] can be selectively targeted to intimal macrophages and smooth muscle cells recruited during formation of hyperplasia via a receptor mediated mechanism. METHODS: In this study, the photosensitizer chlorin e6 (Cle6) was conjugated to mal-BSA in a rat model of intimal hyperplasia, then tested the efficacy of the ligand conjugation to photosensitizer (mal-BSA/Cle6) in PDT of intimal hyperplasia. Arterial wall injury was produced by a balloon catheter pulled through the abdominal aorta of the rat to create a model of intimal hyperplasia. Fluorescent compounds were injected two weeks after injury. RESULTS: Four hours after injection, the intensity of fluorescence achieved with injection of mal-BSA/Cle6 was higher for intimal hyperplastic lesions as compared to control areas. BSA-Cle6 unconjugated did not demonstrate such delivery. Two weeks after balloon injury, the injured aorta was irradiated externally with an argon pumped dye laser four hours following the photosensitizer injection. We employed two total radiant exposures: 20 J/cm2 and 40 J/cm2. Forty-eight hours after PDT, the arteries were examined histologically. Intimal hyperplastic cells were significantly reduced by PDT in the mal-BSA/Cle6 injected group (40-100%) versus the Cle6 group (0-20%). CONCLUSIONS: Mal-BSA/Cle6 is taken up efficiently by a scavenger pathway, localizes in areas of intimal hyperplasia, and functions as a photosensitizer for PDT. PMID- 9972887 TI - Residual inflammatory process after aortoiliac reconstructive surgery. AB - BACKGROUND: The aim of the present study was to investigate the inflammatory reaction and its evolution in patients who underwent a prosthetic vascular procedure. Moreover the participation of this chronic process, during the follow up, as a promoting or a consequence of vascular injury must be discussed. METHODS: Thirty-four patients were enrolled in the study. All patients had an aortic disease and underwent a prosthetic vascular procedure. Preoperative exclusion criteria were an emergency situation, diabetes, infection, chronic inflammatory disease, cancer and hemopathy. Postoperative exclusion criteria were the same together with abdominal complications and additional surgery during the follow-up. The inflammatory process was investigated with the measurement of blood acute phase proteins, haptoglobin, alpha1-glycoprotein acid, C-reactive protein and interleukin-6, before, immediately after surgery and several months after surgery. RESULTS: An increase in acute phase proteins was not observed to the same extent for all the studied patients. Before the surgical procedure, chronic inflammatory process was revealed by an increase in haptoglobin (52.9 p 100) and alpha1 glycoprotein acid (52.9 p 100) whereas increase in C-reactive protein (26.4 p 100) and interleukin-6 (92 p 100) are related to an acute process. Later after surgery, the chronic inflammatory process remained but differed from the observed process before surgery only by haptoglobin (61.7 p 100) and interleukin-6 (47 p 100). CONCLUSIONS: The presented results, observed during the follow-up of vascular surgery focused on persistent inflammatory process and the surgical procedure did not modify the time course of this process. The evolutionary disease could be considered as chronic and independent of the local effect. PMID- 9972888 TI - Reoperation after repair of type A and B dissecting aneurysm. AB - BACKGROUND: In the late postoperative period after repair of an aortic dissection or dissecting aneurysm, reoperations may be required. The interval to reoperation, size and location of intimal tear, and results of reoperation were evaluated. METHODS: Between January 1982 and April 1997, 138 patients underwent surgery for Stanford type A (90 patients) or type B (48 patients) dissections of the aorta. The entire aorta was evaluated in postoperative follow-up by computed tomography and magnetic resonance imaging for 6 months to 15 years. Reoperations were performed in 14 (10.1%) patients with changes in the aneurysms at the site of the initial repair or in the distal aorta. Selective cerebral perfusion or retrograde cerebral perfusion with deep hypothermia was used in the repair of the ascending, arch, and distal arch aneurysms. Reoperations included aortic root reconstruction (n=3), resection of a pseudoaneurysm (n=1), and replacement of the ascending aorta (n=1), arch (n=5), descending aorta (n=2), thoracoabdominal aorta (n=1), or abdominal aorta (n=1). Secondary reoperations were performed in four patients (replacement of the arch [n=2], thoracoabdominal aorta and abdominal aorta). Consequently two patients had subtotal aortic replacements. The aneurysms were caused by an anastomotic leak, a new intimal tear following aortic cross clamping, a second intimal tear in the distal arch or abdominal aorta, and Marfan syndrome. RESULTS: Two patients (2/18 11.1%) died of bleeding or low output syndrome. Two patients died of graft infection or prosthetic valve infection 3 months after surgery respectively. CONCLUSIONS: 1) The surgical results of reoperation for type A and B dissections were good. 2) Close postoperative follow up of the patent false lumen in the entire aorta was necessary. 3) At the initial operation, total resection of the intimal tear in the aortic arch in low-risk patients reduced the risk of reoperation. PMID- 9972889 TI - Surgical treatment of atherosclerotic lesions of subclavian artery: carotid subclavian bypass versus subclavian-carotid transposition. AB - BACKGROUND: The aim of this retrospective study is to analyze the short and long term results of two different surgical treatments in patients with subclavian lesions: common carotid-subclavian artery bypass (CSB) versus transposition of subclavian artery on the common carotid artery (SCT). METHODS: From 1981 until 1995, 40 non randomized patients with symptomatic subclavian steal underwent 20 CSBs and 20 SCTs. Risk factor rates were equally balanced in the two groups. Surgery was carried out routinely under general anesthesia, with electroencephalic continuous monitoring. Patency of revascularization was assessed by physical examination, brachial blood pressure determinations, ultrasound sonography and angiography whenever recurrence of symptoms developed or when the function of repair was in doubt. Patients were examined every year. In Spring 1996 (range 9-189 mos, average 7 years) a general clinical-instrumental follow-up was performed. RESULTS: In the short term (<30 days) mortality was 5%: one death (5%) for pulmonary embolism in a patient with CSB and one for myocardial infarction in a patient with SCT. The early thrombosis rate was 5% (1 CSB and 1 common carotid artery distal to a patent SCT). During follow-up 10 patients (25%) died and 6 were lost. The six-year actuarial patency rate was 100% for SCT and 66% for CSB. Moreover there were 3 thromboses of the vertebral artery homolateral to patent CSBs. CONCLUSIONS: In conclusions SCT should be considered the surgical technical choice for the treatment of proximal subclavian artery lesions. PMID- 9972890 TI - The use of arterial allografts in aortic graft infections. A three year experience on eighteen patients. AB - BACKGROUND: We describe our experience in the treatment of aortic graft infections by replacing them with arterial homografts as suggested by the good results recently described. METHODS: Between March 1994 and March 1997 eighteen patients with infections of the aortofemoral bifurcation segments have been treated. All patients underwent a complete explantation of the infected graft and an in situ revascularization with arterial homograft harvested in multiorgan removal. Eight segments were freshly preserved, 10 were cryopreserved. Four patients were operated as emergencies, of which 3 for aorto-enteric fistulas. All others presented a serious septic state. RESULTS: Three patients died in the early postoperative period: one of acute infarction and two of homograft related causes. In the follow-up there was only one death from acute infarction, a branch occlusion and two allograft enteric fistulas successfully treated by surgery. All surviving patients are submitted to periodical haemodynamic and tomographic control with an average follow-up of 22 months (range 3 months to 3 years) and there has been no allograft degeneration so far. CONCLUSIONS: The use of homologue arterial allografts has shown good results in the treatment of serious aortic graft infections resulting in adequate peripheral vascularization. There have been no significant degenerations to date, either in fresh or cryopreserved allografts. PMID- 9972891 TI - Dissecting aortic aneurysm involving an anomalous right subclavian artery and isolated left vertebral artery: case report and review of the literature. AB - A 54-year-old hypertensive woman was admitted with severe interscapular back pain. A chest radiograph showed marked widening of the mediastinum. Aortography demonstrated a DeBakey type III, a thoracic aortic dissection and an anomalous right subclavian artery which was associated with an isolated left vertebral artery. The patient underwent aortic arch replacement with 5 branches and made an uneventful recovery. As far as we can determine, this is the first reported occurrence of these anomalies together with acquired disease of the aorta. PMID- 9972892 TI - Bilateral subclavian artery aneurysms with pseudocoarctation of the aorta. Case report and review of the literature. AB - Subclavian artery aneurysms are rare. They occur predominantly on the right side. The most frequent cause of proximal subclavian artery aneurysm is atherosclerosis. An aneurysm of the left subclavian artery with normal origin is less common, and it is extremely rare when associated with an aortic coarctation. This report describes the first case of bilateral subclavian artery aneurysms associated with a pseudocoarctation of the aorta. Successful resection of the left subclavian artery aneurysms and the pseudocoarctation of the aorta was achieved using partial cardiopulmonary bypass. PMID- 9972893 TI - Coronary revascularization and abdominal aortic aneurysm repair in a patient with Behcet's diseases. AB - Behcet's disease is a systemic disease characterized by oral aphta, genital ulcer, and ocular lesion. Arterial involvement is an uncommon complication of Behcet's disease, and it most frequently affects the abdominal aorta followed by the femoral artery and the pulmonary artery. Coronary lesions in Behcet's disease have been little reported in the literature. In this communication, we present a case with coronary artery stenosis and with subsequently developed supra-renal abdominal aortic aneurysm. The coronary lesions were revasculized with gastroepiploic artery, right internal mammary artery, and saphenous vein graft. Abdominal aortic repair was performed with partial cardiopulmonary stand by, because of the risk of coronary ischemia during the cross clamp including the celiac artery. To our knowledge, this is the first report of successful repair of combined lesions of the coronary and the abdominal aorta in a patient with Behcet's disease. PMID- 9972894 TI - Aneurysms of the supra-aortic trunks in Takayasu's disease. Report of two cases. AB - Takayasu's arteritis is a chronic inflammatory disease of unknown etiology, which affects the aorta and its branches. The resulting lesions can be of steno occlusive or aneurysmatic type; the latter form is relatively rare. The authors report 2 cases which came under their observation for treatment. The first was a young man of 22 years with aneurysm of the common right carotid artery and of the subclavian left intrathoracic artery. The carotid aneurysm was operated first; arterial reconstruction was ensured by means of a dacron bypass as the saphenous vein was not usable. Three months later, exeresis of the subclavian aneurysm was performed with a left thoracotomy in the IV space. The postoperative course was uneventful and no untoward event has been observed during follow-up (15 months). The second case was a young girl of 16 years with poststenotic aneurysmatic dilatation of the anonyma artery, tight stenosis of the left renal artery and occlusion of the right renal artery. The patient underwent median sternotomy and removal of the aneurysmatic wall together with the stenosis, and a dacron patch was applied. During preoperative angiography, the stenosis of the left renal artery had been treated with PTA; one month after the first operation, a right aorto-renal bypass was fashioned with the saphenous vein. Postoperative stay was free from complications on both occasions and complete normalization of the pressure values was obtained, which persists after 12 months. PMID- 9972895 TI - Percutaneous embolization of an isolated hypogastric artery aneurysm. A case report. AB - We describe a case of an isolated aneurysm of the left hypogastric artery which came under our observation because of a syndrome of compression on the homolateral iliac vein. Having excluded the presence of aneurysms in other sites, it was decided to perform a percutaneous embolization of the hypogastric aneurysm. The follow-up revealed the disappearance of the compression on the ipsilateral iliac vein and a 30% reduction in the diameter of the thrombosed aneurysm. The method limited invasiveness, the reduction in volume of the aneurysmal mass, the disappearance of compression problems, and the shortened hospitalization time support the choice of embolization treatment. PMID- 9972896 TI - Successful surgical management of a ruptured abdominal aortic aneurysm in a renal transplant patient. A case report. AB - With extended indications for renal transplantation and increasing survival, it can be expected that atherosclerotic vascular disease in the post-transplant patient will become more frequent. The authors report a case of a ruptured abdominal aortic aneurysm in a renal transplant recipient. A temporary axillo femoral shunt was used to maintain perfusion of the renal graft during aortic cross-clamping. They review the literature and discuss the available methods for preserving renal function. PMID- 9972897 TI - Treatment of extracranial internal carotid artery aneurysm with resection and external carotid artery bypass. AB - The authors report a case of extracranial internal carotid artery aneurysm with resection of aneurysm and bridging a defect by using the external carotid artery after ligation of its distal end. This technique proposes to prevent neointimal hyperplasia and anastomotic stenosis. PMID- 9972898 TI - Fashioning of aortic isthmoplasty patch. A mathematical model. AB - BACKGROUND: Patch enlargement of the aortic isthmus in congenital coarctation of the aorta (aortic isthmoplasty) has been extensively performed since its introduction in 1957. Even after forty years, the size and shape of the prosthetic patch used as an on a graft is still determined, most of the time, empirically through eyeballing. Not infrequently, it has resulted in an ugly looking repaired aortic segment or with a significant residual systolic gradient across it. These twin problems have called for a mathematical model for designing the patch more precisely. METHODS: The model envisages a patch of the shape of an asymmetric octagon whose cranio-caudal length equals the distance from a point 8 mm on the proximal aorta to a point 8 mm on the distal dilated aorta on either side of the coarcted segment. The side to side length of the patch is determined by first subtracting the circumference of the narrowest part of the coarcted segment from the circumference of the distal dilated portion of the aorta and then adding 4 mm more. The larger slant sides of the octagon are obtained by joining the four smaller sides, of 8 mm in length each. Since July 1993 this mathematical model has been employed in 7 patients to prepare the exact size and the shape of the tightly woven low porosity Dacron patch. RESULTS: In each instance a neat cylindrical aorta was obtained without any measurable post-repair systolic pressure gradient across the repaired site. CONCLUSIONS: In view of these very satisfying results, we believe that this mathematical model of tailoring the patch has succeeded in converting the patch-aortoplasty procedure for coarctation of the aorta into a precise and hemodynamically fully corrective operation. PMID- 9972899 TI - Adult respiratory distress syndrome following cardiopulmonary bypass: incidence, prophylaxis and management. AB - BACKGROUND: In this retrospective study, we have examined the incidence and the predictors of ARDS (adult respiratory distress syndrome), in patients undergoing coronary artery bypass (CABG) surgery on cardiopulmonary bypass (CPB). The prophylactic and therapeutic measures that were used in this series were also evaluated. METHODS: Between January 1988 and January 1995, 4318 consecutive patients undergoing an isolated and a primary CABG procedure were included. Patients with poor left ventricular function, congestive heart failure (CHF), renal failure and with an abnormal chest radiogram were excluded. RESULTS: The independent predictors of ARDS were: recent cigarette smoking, advanced COPD (chronic obstructive pulmonary disease) and emergency surgery. The overall incidence of ARDS was 2.5% and hospital mortality in patients with an established ARDS was 27.7% (30/108). The prophylactic and the therapeutic measures which have been used in this series had no significant impact on the incidence and hospital mortality. CONCLUSIONS: In view of a high perioperative mortality in patients with established ARDS, a mandate for a regular use of prophylactic and therapeutic measures that are based on its pathophysiology, clearly exists. PMID- 9972900 TI - The stimulation of neoangiogenesis in the ischemic human heart by the growth factor FGF: first clinical results. AB - BACKGROUND: This paper is a report of our clinical experience with the human growth factor FGF as applied to the ischemic human myocardium. METHODS: After the completion of extensive preliminary animal experiments, the growth factor FGF, obtained from genetically manipulated E. coli bacteria and highly purified, was introduced into aortocoronary bypass surgery as an additional therapeutic agent. A double blind study was carried out on 40 patients with CHD, separated into "growth factor" and control groups, each containing 20 members. All the patients were treated for threefold vascular disease, in each case with an IMA bypass for the LAD and single venous bypasses for the RCX and/or RCA. In order to bridge over additional peripheral stenoses in the LAD or one of its branches, human growth factor FGF was injected into the myocardium of those in the growth factor group. Twelve weeks later, the IMA bypasses were selectively demonstrated by intraarterial DSA. These angiographs were then quantitatively evaluated. RESULTS: In all patients of the growth factor group, the formation of new vessels could be demonstrated in the region where FGF had been administered, in a manner strictly reminiscent of our experimental results. A capillary net sprouting from the coronary artery and making further connection with this vessel could be demonstrated, and the computer-supported evaluation of the angiographs showed a significant increase in the blood supply of the region of the myocardium injected. CONCLUSIONS: It is therefore our opinion that employment of the human growth factor FGF represents a useful extension to bypass surgery, particularly for patients with an additional peripheral stenosis that cannot be operatively revascularized. PMID- 9972901 TI - Evaluation of perioperative myocardial tissue damage in ischemically preconditioned human heart during aorto coronary bypass surgery. AB - BACKGROUND: Preconditioning myocardium with short periods of ischaemic stress interspersed with reperfusion increases its resistance to infarction. Ischaemic preconditioning protection occurred in human beings during unstable angina preceding myocardial infarction, during percutaneous transluminal coronary angioplasty and during aorto coronary bypass surgery. The purpose of this study was to test (utilised cardiac troponin T measurement) whether ischaemic preconditioning was able to protect myocardial tissue during the perioperative period and how long that protection lasted. METHODS: Patients were recruited to the preconditioned group (n=29), received 4-min of aortic cross-clamping and 6 min reperfusion prior to CABG performed with intermittent ischaemic arrest and the control group (n=27) received only an ischaemic insult of operating procedure. TnT measurements were determined from blood samples taken before surgery (A), 1 hour after onset of CPB (B), 4 hours (C), 8 hours (D), 12 hours (E), 24 hours (F), 48 hours (G) and 72 hours after CPB (H). RESULTS: Results were expressed as the median, range and standard deviation (SD) of TnT concentration (microg/l). Ischaemic preconditioning decreased TnT concentration with statistical significance 1 hour after onset of CPB (preconditioned B: median 0.12+/-0.25 vs control B: median 0.32+/-0.43, p=0.03). There were notable differences in TnT concentration in C, D, E, F, G, H blood samples between the control and the preconditioned group but with p value of no statistical significance. CONCLUSIONS: These data illustrate that ischaemic preconditioning limits myocardial damage during operative procedure and it may probably afford protection during a postoperative period. PMID- 9972902 TI - Cardiac Troponin T to evaluate myocardial protection via intermittent cold blood or continuous warm blood cardioplegia in coronary artery bypass grafting. AB - BACKGROUND: The aim of our study was to evaluate the efficacy of myocardial protection during coronary artery bypass grafting (CABG) in cold blood intermittent (CBIC) and warm continuous blood cardioplegia (WCBC). To assess myocardial necrosis, Troponin T, a structural protein belonging to the troponin complex, was measured. Troponin T is released in the blood stream 4 hours after myocardial damage, and it does not cross-react with the isomeric form of the skeletal muscle. METHODS: Our study involved 20 consecutive patients, scheduled for isolated CABG. They were divided into two groups: the first group (10 patients; 8 m, 2 f) underwent surgery with the use of CBIC, the second group (10 patients; 9 m, 1 f) with WCBC. The serum levels of cardiac Troponin T (cTn-T) were all <0.2 microg/l before operation. RESULTS: In the CBIC the mean cTn-T peaked on the 1st day after CABG, in the WCBC group the first peak occurred in the 2nd hour after arrival in the intensive care unit, and the second peak occurred on the 4th day postoperatively. The mean serum cTn-T was lower in the WCBC vs CBIC group from the 1st to the 5th day postoperatively, with a statistical difference on the 1st day (p<0.05). In the CBIC group either the cTn T peak values (r=0.77; p<0.02) or area under the concentration curve of cTn-T release (r=0.85; p<0.004), were directly correlated with the aortic cross clamping time. This was not demonstrated in the WCBC. CPK and CK-MB peaked in both groups 6 hours after arrival in the intensive care unit and on the 1st day postoperatively, with higher values at 6 hours in the WCBC group (p<0.05). The CK MB/CPK ratio was significantly lower in the WCBC group at the six hours (p<0.05). CONCLUSIONS: The results of this preliminary study suggest that fewer necrosis markers are released during CABG in the WCBC group; in the CBIC group the release of cTn-T whether measured by peak serum level or by area under the curve, shows a statistically significant correlation with cross-clamping time. Warm blood cardioplegia is safe and supplies adequate myocardial protection during CABG; the more prolonged cross-clamping is, the more myocardial protection is afforded by WCBC. PMID- 9972903 TI - Successful repair of cardio-Behcet's disease with aortic and mitral regurgitation. AB - A case of Behcet's disease with cardiac involvement of aortic and mitral regurgitation is presented. The patient underwent aortic and mitral valve replacement, along with plication of the ascending aorta. Histological examination revealed chronic inflammation with degenerative changes, consistent with Behcet's disease. Anti-inflammatory therapy using prednisolone was maintained throughout the postoperative period. This is the first case of cardio Behcet's disease surgically treated for both aortic and mitral valves with a successful long-term survival. PMID- 9972904 TI - The wandering coronary stent. Case report. AB - Complications associated with coronary stent placement have decreased in recent years. One of the complications involved with this procedure is the possibility that the stent is stripped from the delivery catheter prior to deployment and is lost systemically. This paper reports a rare complication which resulted in vascular insufficiency necessitating surgical intervention. PMID- 9972905 TI - Metastatic renal cell carcinoma invading right ventricular myocardium without caval involvement. AB - We examined a 56-year-old man who presented with dyspnea and lower extremity edema. A 2-D echocardiogram showed a large mass within the right ventricle which spared the right atrium and the inferior vena cava. Pathologic evaluation identified a renal cell carcinoma with sarcomatoid features. The tumor had metastasized to and invaded the right ventricular myocardium without right atrial or caval involvement. This pattern of metastases is rare and suggests that this tumor's aggressive nature contributed to the degree of myocardial invasion as well as the patient's rapid demise. PMID- 9972906 TI - Cardiac lipomas. Description of 3 cases. AB - Cardiac lipomas, extremely rare benign tumours, can develop in the pericardial surface or inside the cardiac chambers. We report three cases, 2 intracardiac (one in the left and right atrium at the level of the interatrial septum and the other in the right ventricle) and one epicardial at the level of the left atrial roof. All patients underwent surgery and are now asymptomatic. PMID- 9972907 TI - Aorto-atrial fistula associated with recurrent aortic dissection after ascending aorta replacement. AB - A 70-year-old woman with a bicuspid aortic valve had undergone ascending aorta replacement for acute DeBakey type I dissection. Computed tomography and aortography 2 months after the operation revealed a thrombosed false lumen in the ascending aorta proximal to the prosthetic graft. However, recurrence of dissection was found at the aortic root proximal to the graft 4 years after the initial operation. Significant aortic stenosis was also noted. Despite intensive medical treatment, she had refractory and progressive heart failure. At the second surgery, an aorto-right atrial fistula, which probably was responsible for the severe heart failure was revealed. Closure of the aorto-right atrial fistula, and aortic root replacement were performed using Piehler's method, with a composite graft. The etiology and management of this rare case are discussed. PMID- 9972908 TI - Acquired aortopulmonary fistula. A case report. AB - A 63-year-old male patient with no prior history of heart disease was admitted in acute heart failure with diagnosis of pulmonary thromboembolism. 2D echocardiography and color-Doppler echocardiography showed a severe aortic stenosis associated with an acquired aorto-pulmonary fistula bridging the ascending aorta and the main pulmonary artery. The diagnosis was confirmed by aortography. The patient underwent replacement of the aortic valve with a bileaflet mechanical valve. The fistula was obliterated with a Dacron patch anchored on the edges of its aortic opening. He did well postoperatively and was discharged with no complaint. PMID- 9972909 TI - Wash out technique for proximal anastomosis in atherosclerotic ascending aorta. AB - BACKGROUND: Especially among elderly patients embolisms originating from atheromatous plaques in the ascending aorta are responsible for cardiac and cerebral events during coronary bypass surgery. Unfortunately smooth atheromatous degeneration of the aorta often can not be detected even by transoesophageal echocardiography. METHODS: In four patients with unexpected atheromatous material of the punched ascending aorta the so called "wash out technique" was performed. A side-to-end anastomosis between a segment of vein and the partially clamped ascending aorta was performed. For several minutes the ascending aorta was left to bleed through the venous stump. Without further manipulation of the ascending aorta the coronary bypass graft was completed by an end-to-end anastomosis between the venous stump and the venous graft. Oral anticoagulation in combination with a low dose platelet antiaggregation drug was given for at least one year. RESULTS: All patients had an uncomplicated postoperative course, especially with regard to neurological damage or ECG changes. CONCLUSIONS: In patients with unexpected atheromatous pathology of the ascending aorta the "wash out technique" of coronary artery bypass grafting minimises direct embolisation into the cardiac area perfused by the new bypass grafts. PMID- 9972910 TI - Technical considerations for partial left ventriculectomy (Batista operation). AB - The surgical technique for partial left ventriculectomy (Batista operation) as performed in two surgical centers is described. This surgical remodeling of the left ventricle restores the abnormal geometric configuration produced by the dilated failing heart. It accomplishes a reduction of the left ventricular end diastolic diameter and end-diastolic volume with consequent increase in left ventricular function. This procedure represents the newest surgical approach in the management of patients with end-stage cardiomyopathy; it can be used as a bridge to transplantation or perhaps as a definitive form of therapy, particularly in those patients in whom heart transplantation is contraindicated. This report describes technical guidelines to avoid serious intraoperative and postoperative complications directly associated with this technique. PMID- 9972911 TI - Combined use of single and double-cross steel wires for closure of midline sternotomy. AB - BACKGROUND: We describe an improved technique for sternal closure which is performed using combined single and double-cross steel wires. We made a mechanical study of these single and double-cross shapes considering the effects of applied transverse and longitudinal shearing forces. METHODS: We used this technique in 80 patients who underwent coronary surgery with the use of bilateral internal mammary arteries. RESULTS: Among them no major wound complications occurred, and in all cases a firm stabilization of the sternum was achieved. CONCLUSIONS: We therefore consider this technique of sternal closure easy, safe and effective, also in patients considered at risk for sternal dehiscence. PMID- 9972913 TI - Lung volume reduction surgery for severe emphysema. AB - BACKGROUND: We report mid-term results after 25 consecutive lung volume reduction operations (LVRS) for the treatment of severe dyspnea due to advanced emphysema. METHODS: STUDY DESIGN: patients were studied prospectively up to 12 months after surgery. SETTING: preoperative evaluation, surgery and postoperative care took place in our university hospital. PATIENTS: patient selection was based on severe dyspnea and airway obstruction despite optimal medical treatment, lung overinflation and completed rehabilitation programme. PATIENTS with severe hypercarbia (PCO2>50 mmHg) were excluded. Nineteen rehabilitated patients who fulfilled our inclusion criteria but postponed or denied LVRS were followed up clinically. INTERVENTIONS: LVRS was performed bilaterally in 22 patients (median sternotomy) and unilaterally in 3 patients (limited thoracotomy). MEASURES: Outcome was measured by dyspnea evaluation, 6-minute-walking distance and pulmonary function tests. RESULTS: Twelve months postoperatively dyspnea and mobility improved significantly (MRC score from 3.3+/-0.7 to 2.12+/-0.8, 6-min walk from 251+/-190 to 477+/-189 m). These results were superior compared to the results of the conservatively treated patients. Significant improvement could also be documented in airway obstruction (FEV1 from 960+/-369 to 1438+/-610 ml) and overinflation (TLC from 133+/-14 to 118+/-21% predicted and RV from 280+/-56 to 186+/-59% predicted). CONCLUSIONS: LVRS is an effective and promising treatment option for selected patients with end-stage emphysema and could be offered as an alternative and / or bridge to lung transplantation. PMID- 9972912 TI - Spinal cord protection by papaverine and intrathecal cooling during aortic crossclamping. AB - AIM: To extend the safe period of aortic crossclamping in the porcine model by intrathecally dilating the spinal arteries, with cooling of the spinal cord, or using selfoteL METHODS: Experimental design and setting: prospective domestic laboratory pig study. INTERVENTIONS: fifteen animals were assigned to a control group (C, N=5), intrathecal papaverine plus spinal cord cooling group (IP+C, N=5), or selfotel group (S, N=5). In the IP+C group, a lumbar laminectomy was performed and an intrathecal catheter placed for intrathecal injection of papaverine and perfusion with cold Ringer's solution (4 degrees C) prior to aortic crossclamping. In the selfotel group, 20 mg/kg of selfotel was administered 30 minutes before aortic crossclamping. In all 15 animals, the aorta was crossclamped for 60 minutes at normothermia. MEASURES: immediately after the operation and 24 hours later, lower limb function was evaluated. RESULTS: All five control animals were paralyzed; all 5 IP+C animals could stand or walk (p=0.004 versus control); and in the selfotel group, one had paraparesis, three had paraplegia and one died before evaluation (p=n.s.) CONCLUSIONS: The combination of intrathecal papaverine to dilate spinal arteries and prevent spasm from the cold solution plus intrathecally cooling the spinal cord appears to extend the period of safe aortic crossclamping. Selfotel, in this model of extended, severe, spinal cord ischemia, was ineffective. PMID- 9972914 TI - Management of pneumothorax in children. AB - BACKGROUND: The efficacy of tube thoracostomies inserted at the sixth intercostal space at midaxillary line was evaluated retrospectively in children. METHODS: Ninety-seven children with pneumothorax, treated by tube thoracostomy were taken into the study. There were 67 male and 30 female patients with a mean age of 6.5 years (range 1 days to 15 years) RESULTS: Pneumothorax was located at the right side in 50 (51.5%), and at the left in 38 (39.1%) of the cases. Bilateral pneumothorax was found in 9 additional patients (9.2%). All patients were treated with tube thoracostomy placed in the pleural cavity at the sixth intercostal space at the mid-axillary line. Postoperative course was uneventful and no complication was encountered at any of the patients. CONCLUSIONS: On the basis of these data we suggest that all thoracostomy tubes should be inserted on the sixth intercostal space where both air and the accumulating fluid can be reached. The insertion of the thoracostomy tube at the second intercostal space must be avoided since it carries a high risk of subclavian vein injury in small children, and also a secondary tube is frequently required to drain the accompanying intrapleural fluid. PMID- 9972916 TI - A case of traumatic pericardiophrenic rupture. AB - An unusual case of traumatic pericardiophrenic rupture is presented. The defect was limited to the central tendon of the diaphragm, with herniation of the stomach into the pericardial sac. A correct preoperative diagnosis was not made because laparotomy was quickly performed for splenic rupture. Successful operative repair of the tear was performed, with interrupted reabsorbable sutures. The case is discussed and the management of patients with these rare lesions is reviewed. PMID- 9972915 TI - Alloplastic sternal replacement in malignant sternal tumors. Case report and review of the literature. AB - Although not seldom as a palliative procedure, the preferred treatment of locally recurrent breast cancer or chest wall involvement by metastases is full-thickness chest wall resection. For closure and coverage of the defect various techniques are described. Autoplastic reconstruction is indicated for smaller defects, while larger defects usually require alloplastic materials, especially in case of chest instability after resection. We report the case of a 55-year-old female who developed a locally recurrent breast cancer with infiltration of the sternum 4 years after left sided ablation. En bloc resection of the chest wall including the complete sternum was followed by replacement with a computer-aided custom made polyethylene sternal prosthesis. With this procedure we stabilized the chest wall with protection of the underlying organs, avoided prolonged postoperative ventilation and achieved a satisfying cosmetic result. PMID- 9972917 TI - Occult Boerhaave's syndrome without vomiting prior to presentation. Report of a case. AB - Boerhaave's syndrome (spontaneous esophageal perforation) is an uncommon clinical entity that frequently presents with an antecedent history of marked vomiting followed by chest or abdominal pain. We report a case of spontaneous rupture of the esophagus in 53-year-old male who was referred to our hospital with a chest discomfort. A chest radiogram revealed pleural effusion and pneumomediastinum. Nine hours after onset, the diagnosis of Boerhaave's syndrome become evident. She underwent operative repair and, after a prolonged stay, was discharged in relatively good condition 55 days after admission. The absence of vomiting prior to presentation is the distinguishing feature of this particular case. This is the seventh case in the English literature to our knowledge. PMID- 9972918 TI - An endometrial nodule in the lung without pelvic endometriosis. AB - We present a 55-year-old woman with an intrapulmonary nodule diagnosed as pulmonary endometriosis by video-assisted thoracic surgery. Ectopic endometriosis in the parenchyma of the lung is relatively rare, especially in this case, where there was neither pelvic endometriosis nor clinical symptoms. PMID- 9972919 TI - A case of ruptured descending thoracic aortic aneurysm into the right pleural cavity: importance of preoperative drainage of the right pleural cavity. AB - We present an unusual case of a ruptured descending thoracic aortic aneurysm into the right pleural cavity of a patient with pectus carinatum. The presence of pectus carinatum played an important role in the development of the aneurysm at the atypical site and the rupture into the right pleural cavity. A small amount of right pleural bleeding on admission can increase and develop to massive hemothorax until emergency operation. Massive bleeding in the right pleural cavity where the dependent lung is located causes atelectasis and increased shunt fraction under one lung ventilation. Therefore, continuous drainage of the right pleural cavity is essential to prevent serious hypoxia during graft replacement in a case of ruptured descending thoracic aneurysm into the right hemithorax. PMID- 9972920 TI - Long-term results of primary repair without graft replacement for acute ascending aortic dissection. PMID- 9972921 TI - A risk characterization for atrazine: oncogenicity profile. AB - An extensive safety database has been developed for the chlorotriazine herbicide, atrazine. The results from five oncogenicity studies conducted in the Sprague Dawley rat, two studies in the Fischer 344 rat, and two studies in the CD-1 mouse were reviewed. No increase in the incidence of tumors of any type was observed in male or female Fischer 344 rats, male or female CD-1 mice, or male Sprague-Dawley rats fed atrazine at a maximum tolerated level in their diet for 24 mo. Female Sprague-Dawley rats fed atrazine at levels of 400, 500, and 1000 ppm developed mammary tumors earlier than did the control group. The incidence of female Sprague-Dawley rats with mammary tumors after 24 mo of treatment was statistically increased at feeding levels of > or = 70 ppm in 1 study and at 400 ppm in a second study, whereas there were no significant differences between the treated and the control group in 3 other studies. No increase in tumors of any type was observed in ovariectomized female Sprague-Dawley rats after 24 mo of atrazine treatment at the highest level tested, 400 ppm. Therefore, the mammary tumor response in female Sprague-Dawley rats following the administration of high levels of atrazine appears to be due to an acceleration of the normal reproductive aging process resulting in increased exposure to endogenous estrogen and prolactin. The Sprague-Dawley rat differs from the Fischer 344 rat, the CD-1 mouse, and humans in the endocrine control mechanisms affecting reproductive senescence and the development of the mammary tumors during aging. These data indicate that the carcinogenic effect of high doses of atrazine observed in the female Sprague-Dawley is a strain-, sex-, and tissue-specific response that does not have biological relevance to humans. PMID- 9972922 TI - Effects of indoor environmental factors on risk for acute otitis media in a subtropical area. AB - The objective of this study was to examine the relationship between indoor environmental factors and acute otitis media in a subtropical area. A case control study was performed using participants from a prevalence survey that included 219 school children with acute otitis media and 219 age- and gender matched controls. The study was confined to 4164 primary school children aged 6 12 yr attending 8 primary schools in Kaohsiung rural municipalities who participated in a prevalence study of the health effects of an indoor environment. An acute otitis media case was defined as a child with acute symptoms (presenting with earache, fever, irritability, and/or discharge from the ear) diagnosed by a physician in the previous year. Controls selected from the same school did not have chronic or acute respiratory illness or an ear-related illness during the same period. Information regarding the home environment was obtained using a structured written questionnaire, completed by the parents of the children. Of the many indoor environmental factors included in this study, only living in a home with indications of dampness (mold, flooding, home dampness) showed an association with acute otitis media. It was concluded that dampness in the home is a new public health issue in subtropical areas. PMID- 9972923 TI - Ethanol co-exposure increases lethality of allyl alcohol in male Sprague-Dawley rats. AB - Since allyl alcohol and ethanol are both metabolized by alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH), ethanol could affect allyl-alcohol induced toxicity under in vivo coexposure conditions. Male Sprague-Dawley rats were treated with ethanol (2 g/kg, i.p.) simultaneously or 2 h before with allyl alcohol (40 mg/kg, i.p.). Coexposure to allyl alcohol and ethanol resulted in neither enhancement nor protection in allyl alcohol-induced hepatotoxicity at 24 h. However, markedly increased lethality was observed under our coexposure conditions. Pretreatment with 4-methylpyrazole (4-MP) to inhibit ADH did not result in increased lethality to allyl alcohol or ethanol alone, but significantly reduced the lethality of the combined treatment. In contrast, ALDH inhibition increased the lethality of allyl alcohol alone as well as that of the combined allyl alcohol and ethanol treatment. Kinetic studies revealed that combined treatment with allyl alcohol and ethanol resulted in higher blood allyl alcohol levels compared to allyl alcohol alone, and these were accompanied by greater lethality. ADH inhibition increased allyl alcohol blood levels significantly when rats were treated with allyl alcohol alone or allyl alcohol plus ethanol, leading to protection against lethality. In contrast, ALDH inhibition did not affect blood allyl alcohol levels, but resulted in increased lethality. These data suggest a possible role for a metabolite of allyl alcohol, acrolein, in the increased lethality of allyl alcohol and ethanol coexposure in rats. PMID- 9972925 TI - Undergraduate Education in Rheumatology, Challenges for the Millennium. Sentosa, Singapore, June 13-15, 1997. Proceedings. PMID- 9972926 TI - Undergraduate education in rheumatology: challenges for the millennium. PMID- 9972927 TI - Undergraduate medical education in rheumatology in Europe. PMID- 9972924 TI - Inhibition of natural killer cell activity in mice treated with tobacco specific carcinogen NNK. AB - Among the different chemicals present in tobacco and tobacco smoke, 4 (methylnitrosamine)-1-(3-pyridyl)-1-butanone (NNK) is the most potent carcinogen. In the present study the immunosuppressive effect of NNK was investigated in laboratory animals by analyzing the antitumor immune responses. Mice of B6C3F1 strain were treated with different doses of NNK by IP and assayed for natural killer cell activity by the lysis of 51Cr-labeled YAC-1 lymphoma cells. The control mice received physiological saline. The results showed a significant inhibition of natural killer cell activity in the spleen cells of mice treated with 100 or 250 mg/kg NNK. In contrast to the high-dose NNK group, treatment of mice with lower doses of NNK like 10 or 50 mg/kg had no significant effect on the natural killer cell activity. In addition to spleen, the natural killer cell activity was also suppressed in the hilar lymph nodes and lung cells of NNK treated mice. The clearance of 125I labeled YAC-1 tumor cells was also reduced from the lungs of mice injected with NNK. Further, the metastatic potential of B16F10 melanoma cells was significantly higher, as evidenced by the increased lung tumor nodules in the high-dose NNK-treated mice. The decreased antitumor immune response in the carcinogen-treated mice was not due to a decrease of NK cells, because flow cytometric analysis indicated no change in the frequency of NK 1.1+ cells between control and treated animals. However, there was an increased plasma cortisone levels in the carcinogen-treated mice compared to control animals. Injection of mice with poly I:C or interleukin-12 was able to restore natural killer cell activity in the tobacco carcinogen-treated mice. PMID- 9972928 TI - The teaching of rheumatology in undergraduate medical education in France. PMID- 9972929 TI - Undergraduate education in rheumatology in German speaking countries. PMID- 9972930 TI - Education of rheumatic disorders at Dutch medical schools. PMID- 9972931 TI - The present state of undergraduate education in rheumatology in Australia. PMID- 9972932 TI - Undergraduate education in rheumatology in Asian Pacific countries (APLAR). PMID- 9972933 TI - Undergraduate education in rheumatology in Latin America. PMID- 9972934 TI - North American undergraduate education in rheumatology. PMID- 9972935 TI - Undergraduate education in rheumatology in Latin America. PMID- 9972936 TI - Undergraduate education in rheumatology in Brazil. PMID- 9972937 TI - Undergraduate education in rheumatology in Tunisia. PMID- 9972938 TI - Undergraduate rheumatology teaching in Africa. PMID- 9972939 TI - Undergraduate medical education in rheumatology--aims. PMID- 9972940 TI - The American College of Rheumatology Core Curriculum--a problem based learning curriculum: rationale and design. PMID- 9972941 TI - The core curriculum: history and examination. PMID- 9972942 TI - Methods in undergraduate education in rheumatology. PMID- 9972943 TI - Skills development in rheumatology undergraduate and postgraduate curricula. PMID- 9972944 TI - Attitude education in rheumatology. PMID- 9972945 TI - Learning objectives of undergraduate medical education in rheumatology. PMID- 9972946 TI - The teaching of rheumatology in a graduate entry medical school. PMID- 9972947 TI - Video supported small group learning: problem solving and clinical reasoning. PMID- 9972948 TI - The use of trained arthritis patients in the instruction of the musculoskeletal examination. PMID- 9972949 TI - Interactive computer programs. PMID- 9972950 TI - Rheumatology training for general practice. PMID- 9972951 TI - Methotrexate and radiographic disease progression in patients with rheumatoid arthritis. PMID- 9972952 TI - Psychological distress and healthcare seeking behavior: caution warranted in interpreting data. PMID- 9972953 TI - Enigmas of adrenal androgen and glucocorticoid dissociation in premenopausal onset rheumatoid arthritis. PMID- 9972954 TI - Circulating levels of matrix metalloproteinases MMP-3 and MMP-1, tissue inhibitor of metalloproteinases 1 (TIMP-1), and MMP-1/TIMP-1 complex in rheumatic disease. Correlation with clinical activity of rheumatoid arthritis versus other surrogate markers. AB - OBJECTIVE: To investigate whether plasma levels of matrix metalloproteinases 3 (MMP-3, stromelysin), MMP-1 (collagenase), tissue inhibitor of metalloproteinases 1 (TIMP-1), and MMP1/TIMP-1 complex (MT complex) are specifically elevated in erosive joint diseases compared to nonerosive rheumatic diseases, and to assess how these markers reflect the clinical activity of rheumatoid arthritis (RA) compared to circulating cytokines and markers of connective tissue turnover as well as established variables [C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and rheumatoid factor titer]. METHODS: Plasma levels of MMP-3, MMP-1, TIMP- 1, and MT complex were determined by ELISA. One hundred fifteen patients with RA, 20 with osteoarthritis (OA), 28 with psoriasis arthritis (PsA), 24 with ankylosing spondylitis (AS), 3 groups with systemic autoimmune diseases, and 30 healthy controls were analyzed. In patients with RA routine laboratory variables, circulating inflammatory cytokines [interleukin 1 (IL-1), tumor necrosis factor-alpha (TNF-alpha), and IL-6], collagen degradation products, and markers of bone formation were determined in parallel and were correlated to 4 variables of clinical activity. RESULTS: MMP-3 levels were markedly elevated in RA compared to controls and OA, but also in all other groups, including 26 patients with systemic lupus erythematosus (SLE). MMP-1 levels were significantly elevated in RA, but also in OA, PsA, SLE, and mixed connective tissue disease. In contrast, MT complex was elevated in RA only. TIMP 1 was not different from controls. CRP levels, MMP-3, and ESR correlated best with clinical activity of RA. In contrast, there was no correlation of IL-1 and TNF-alpha and only a weak correlation of IL-6 with clinical measures. Among variables of connective tissue turnover, only pyridinoline and deoxypyridinoline crosslinks were weakly correlated with disease activity. CONCLUSION: Elevated MMP 3 and MMP-1 levels are not specific for RA or for erosive joint diseases in general. In contrast, elevated MT complex levels were observed in patients with RA. However, the correlation of MT-1 with clinical data was weaker than that of MMP-3. Elevated MMP-3 levels reflected disease activity of RA better than cytokine levels or markers of connective tissue turnover. However, MMP-3 levels do not exceed the association of CRP with clinical activity. PMID- 9972956 TI - Radiologic progression in early rheumatoid arthritis treated with methotrexate. AB - OBJECTIVE: To evaluate radiologic progression in patients with early rheumatoid arthritis (RA) receiving methotrexate (MTX) as the first slow acting drug. METHODS: An open, prospective study of 29 patients with RA (21 F, 8 M, mean age 48.5+/-15.4 yrs). The mean duration of RA was 6.6 (2-60) months; and rheumatoid factor was present in 11 cases. Clinical, biological, and radiographic evaluations were done before the start of MTX treatment and after 13+/-3.8 months. Radiographs of hands and wrists were blindly studied by 2 physicians, using Larsen's and modified Sharp's methods. There was a significant correlation for the scores of the 2 physicians evaluated by kappa coefficient. Radiographic evolution was defined as an increase of 15 points in the radiologic score by each method used. RESULTS: Patients showed significant clinical improvement after one year of MTX treatment. Despite clinical and biological improvement, significant mean radiographic progression was noted, with Larsen's method (p = 0.001) and Sharp's method (p = 0.034), without reaching the maximum score. However, using the definition of radiographic progression, the radiologic scores indicated stabilization in 23 patients with Larsen's method and in 24 patients with Sharp's method. CONCLUSION: This study revealed mild radiographic progression in early RA patients treated with MTX for one year. Further controlled studies are needed. PMID- 9972955 TI - Paucity of radiographic progression in rheumatoid arthritis treated with methotrexate as the first disease modifying antirheumatic drug. AB - OBJECTIVE: To determine disease progression in patients with rheumatoid arthritis (RA) using methotrexate (MTX) as the first disease modifying antirheumatic drug (DMARD). METHODS: Patients with RA treated with MTX as their first DMARD and in whom hand/wrist radiographs prior to MTX administration had been obtained and who had received MTX for at least 10 months were evaluated radiographically for disease progression. Coded radiographs were read for erosions by 2 experienced readers using the modified method of Sharp. Erosion scores and rate of progression (per month) were calculated. RESULTS: Of 24 patients studied, baseline radiographs showed erosions (one or more) in 11 and none in 13. Patients with and without erosions at baseline had comparable demographic and clinical features, although patients with erosions had longer disease duration and higher rheumatoid factor positivity than those without erosions (statistically nonsignificant, however). Half of all patients showed no progression; 73% of those patients with erosions at baseline but only 31% of those without erosions at baseline progressed (p = 0.049); progression rates were 0.017 (+/-0.033) and 0.049 (+/-0.078) for the 2 groups (p = 0.040). CONCLUSION: Patients with RA starting MTX before erosions have occurred are less likely to develop them; these patients also experienced a lesser degree of disease progression than patients who started MTX with erosions already present. PMID- 9972957 TI - Influence of a ceiling effect on the assessment of radiographic progression in rheumatoid arthritis during the first 6 years of disease. AB - OBJECTIVE: To evaluate at what disease duration and to what extent a ceiling effect, due to reaching maximum scores for erosions (E) and/or joint space narrowing (JSN) in separate joints, started to influence the assessment of radiographic progression according to the modified method of Sharp, in patients with recent onset rheumatoid arthritis (RA). METHODS: Prospective followup study of 87 patients with classical or definite RA, joint symptoms <1 year at study entry. Radiographs of hands and feet were made at study entry (Time 0), after 3 (T3), and after 6 years (T6) of followup. Assessment of radiographic progression according to the Van der Heijde modification of Sharp's method. The scores for E and JSN were analyzed separately in the individual groups of joints. Percentages of E joints, of joints with JSN, and of joints with maximum scores were assessed at T0, T3, and T6. The relative risks for the development of radiographic damage and of maximum scores were assessed for the individual joints. An approximation of the magnitude of the ceiling effect was calculated. RESULTS: After a disease duration of 6 years, a significant influence of a ceiling effect on the mean radiographic progression was found. In some individual patients the ceiling effect appeared to occur earlier. After 6 years, the maximum scores were distributed over 50% of the patients, and 20% of the patients had maximum scores in more than 10 joints without preference for specific localization. CONCLUSION: The ceiling effect appeared to be clinically relevant and should be taken into account when interpreting the effects of disease modifying antirheumatic drugs on radiographic progression in RA during the first years of the disease. Furthermore, it must be accounted for when describing the relationship between radiographic progression and process variables. PMID- 9972958 TI - Hypothalamic-pituitary-adrenal axis function in patients with active rheumatoid arthritis: a controlled study using insulin hypoglycemia stress test and prolactin stimulation. AB - OBJECTIVE: To study the response of cortisol and of prolactin (PRL) to specific stimuli in rheumatoid arthritis (RA). METHODS: We measured the response of cortisol to insulin induced hypoglycemia and of PRL to thyrotropin releasing hormone (TRH) in 10 patients with active RA and in 10 paired control subjects. All were women with regular menstrual cycles. They had never received corticosteroids before the study. The PRL concentration was assessed by chemiluminescence immune assay and the cortisol concentration by radioimmunoassay. RESULTS: The basal serum levels of cortisol (14.47+/-2.5 microg/dl) and PRL (10.1+/-1.3 ng/ml) in the RA group were not significantly different from those of the control group (12.3+/-1.1 microg/dl and 13.7+/-2.4 ng/ml, respectively). The peak value of cortisol after hypoglycemia was comparable in both groups (25.5+/-2.4 microg/dl in RA vs. 26.0+/-1.5 ng/ml in controls). The integrated cortisol response to hypoglycemia expressed as area under the response curve (AUC) did not differ significantly in either group (1927+/-196 in RA vs. 1828+/-84 in controls). The interval-specific "delta" cortisol response was significantly higher for the 30 to 45 min interval in controls compared to patients with RA (9.8+/-0.9 microg/dl vs. 6.1+/-1.1 microg/dl; p = 0.02). The peak of PRL after TRH did not differ significantly in both groups (56.4+/-6.4 ng/ml in RA vs. 66.3+/-7.7 ng/ml in controls) and the AUC of PRL secretion after TRH was comparable in both groups (3245+/-321 vs. 4128+/ 541). CONCLUSION: Our findings suggest that active RA is associated with subtle dysfunction of the hypothalamic-pituitary-adrenal glucocorticoid function and normal PRL secretion. PMID- 9972959 TI - Hypothalamic-pituitary-adrenocortical axis function in premenopausal women with rheumatoid arthritis not treated with glucocorticoids. AB - OBJECTIVE: To assess hypothalamic-pituitary-adrenocortical axis function in patients with rheumatoid arthritis (RA) not previously treated with glucocorticoids in relation to their inflammatory condition and in comparison to healthy controls. METHODS: We evaluated, in 10 premenopausal patients with RA and 7 age matched controls, plasma dehydroepiandrosterone (DHEA), its sulfate (DHEAS), and cortisol concentrations, together with inflammatory cytokine levels [interleukin 6 (IL-6) and IL-12], both in basal conditions and after stimulation with ovine corticotropin releasing hormone (oCRH) and with low dose intravenous (5 microg) adrenocorticotropic hormone (ACTH). RESULTS: DHEA and DHEAS basal concentrations were found to be significantly lower (p<0.05) in premenopausal patients with RA than in controls. As expected, significantly higher basal levels of IL-6 and IL-12 (p<0.05) were found in patients with RA. After the low dose ACTH testing, the DHEA area under the curve value was found to be significantly lower (p<0.01) in patients than controls. Similar results, but without statistical significance, were observed after oCRH stimulation. DHEA levels at basal time showed a significant negative correlation with the erythrocyte sedimentation rate and platelet count, as well as with the Steinbrocker class of the disease (p<0.05). Normal plasma cortisol levels during oCRH and ACTH testing were found in patients with RA in spite of their inflammatory condition. After ACTH testing, IL-6 levels decreased significantly (p<0.05), whereas IL-12 levels were unchanged. No significant changes in IL-6 and IL-12 levels were found after oCRH testing. CONCLUSION: The abnormal androgen concentrations observed during testing in patients with RA might support the implication of adrenal androgens in the immune/inflammatory cytokine mediated mechanisms involved in the pathophysiology and clinical aspects of RA. PMID- 9972960 TI - The posterior tibial tendon and the tarsal sinus in rheumatoid flat foot: magnetic resonance imaging of 40 feet. AB - OBJECTIVE: To investigate the role of the posterior tibial tendon in the flat foot deformity of rheumatoid arthritis (RA). METHODS: Eleven patients with hyperpronated feet and 9 without hyperpronation underwent magnetic resonance imaging (MRI) of the feet and ankles. Radial oblique double echo images provided cross sectional views of the posterior tibial tendon as it coursed behind and under the medial malleolus and inserted beneath the midfoot. RESULTS: Complete tears (Type III) of the posterior tibial tendon were seen in one patient with hyperpronation and in one without hyperpronation. However, partial tears (Types I and II) of the posterior tibial tendon were common, and when Type I-III posterior tibial tendon tears were grouped together, they were seen in 68% of flat feet and in 43% of feet that were not flat. Abnormalities of the tarsal sinus, including cortical erosions and replacement of the normal fat signal with intermediate signal soft tissue, were seen in 74% of flat feet and in 5% of feet that were not flat. CONCLUSION: Posterior tibial tendon tears are common in RA flat feet, but are usually incomplete and are not solely responsible for the flat foot deformity. PMID- 9972961 TI - CpG motif-containing DNA fragments from sera of patients with systemic lupus erythematosus proliferate mononuclear cells in vitro. AB - OBJECTIVE: To characterize DNA in sera of patients with systemic lupus erythematosus (SLE) in terms of size, guanine plus cytosine (G+C) content (by percentage), CpG dinucleotide (CpG) (percentage), and effects on mononuclear cells (MNC). METHODS: Nine DNA clones were sequenced. Oligodeoxynucleotides with the characteristic CpG motif (TTCGAA or PuPuCGPyPy) were examined for their proliferative effect on MNC by [3H]thymidine incorporation, expression of HLA-DR and intercellular adhesion molecule (ICAM)-1 on monocytes by flow cytometry, and mRNA levels encoding interleukin 12 (IL-12) and interferon-gamma (IFN-gamma) by semiquantitative reverse transcription polymerase chain reaction. RESULTS: The size of DNA clones ranged from 87 to 318 bp (mean +/- SD, 177+/-68) and enrichment in G+C and CpG ranged from 34.7 to 69.7% (48.1+/-10.7) and 0.63 to 12.8% (4.0+/-4.1), respectively. Three of 9 clones contained the characteristic CpG motif. Oligonucleotides proliferated MNC, and augmented HLA-DR and ICAM-1 expression in company with an increase of mRNA encoding IL-12 and IFN-gamma. CONCLUSION: Circulating CpG motif-containing DNA fragments in SLE increased mRNA encoding IL-12 and IFN-gamma, which in turn increased HLA-DR and ICAM-1 on monocytes, resulting in MNC proliferation. This mechanism could contribute to the pathogenesis of SLE. PMID- 9972962 TI - Safety of self-injection of gold and methotrexate. AB - OBJECTIVE: We review our experience with safety, efficacy, and practicality of self-administration of gold and methotrexate (MTX) in 40 patients. METHODS: Between 1992 and 1995, 40 patients with rheumatoid arthritis (RA) and psoriatic arthritis (PsA) followed in the drug monitoring clinics of the Mary Pack Arthritis Centre were taught to self-administer parenteral gold or MTX. Self injection education was recommended to patients who were stable and improved taking parenteral gold or MTX, and who had not experienced serious side effects. Charts were reviewed to extract and analyze prospectively collected data regarding safety, efficacy, and compliance. RESULTS: Sixty-five percent of patients performed self-injection and 35% received injections at home from a partner. Side effects in the self-injection patients are similar to those observed in clinic patients receiving drug by nurse administration. One MTX treated patient required treatment for interstitial pneumonitis, which developed after 22 weeks on self-injection. Side effects of self-injection included superficial irritation at the injection site in 2 patients and dosing error in 2 patients with no adverse effects. Seventy percent of gold and MTX treated patients continued self-injection after a mean of 34 months. Patients surveyed for satisfaction identified time saving and convenience as major benefits. CONCLUSION: With basic instruction and close supervision, self-injection of antirheumatic drugs is safe in selected patients. Self-injection reduces utilization of health care services, and is convenient and time and cost-saving to the patient. PMID- 9972963 TI - Quality of life in systemic lupus erythematosus: a controlled study. AB - OBJECTIVE: To assess the quality of life (QOL) of patients with systemic lupus erythematosus (SLE) and to compare it with that of healthy women and patients with primary fibromyalgia (FM). METHODS: QOL was evaluated using the QOL scale, which includes 16 items, each scored on a 7 point scale. Healthy controls were chosen from hospital personnel. RESULTS: The study population comprised 75 female patients with SLE, 50 healthy women, and 30 women with primary FM. Compared to controls, patients with SLE had significantly lower scores for the health, work, active recreation, and independence items. The QOL scores were not associated with disease activity. Patients with SLE and FM had significantly lower scores for the health related items compared with patients with SLE without FM. CONCLUSION: The QOL of patients with SLE was found to be impaired compared with controls. FM adversely affects the QOL of patients with SLE. PMID- 9972964 TI - Three year followup of bone mineral density change in premenopausal women with systemic lupus erythematosus. AB - OBJECTIVE: To measure the change in bone mineral density (BMD, g/cm2) in a female population with systemic lupus erythematosus (SLE) over 3 years, to identify factors predictive of bone loss, including the role of corticosteroid and disease related variables, and to determine the predictive value of urinary collagen crosslinks for bone loss. METHODS: All premenopausal women with SLE who participated in a cross sectional study of BMD in 1994 were invited to undergo a standardized interview, examination, medical record review, and BMD measurement of the lumbar spine and femoral neck by dual energy x-ray absorptiometry. RESULTS: Thirty-two women participated with a mean (SEM) age of 35.2 (1.5) years, duration of SLE of 7.0 (0.8) years, and mean (range) time to followup of 3.2 (2.9 3.4) years. Twenty-one subjects were exposed to corticosteroids during the study period with a mean (range) daily dose of prednisolone of 11.1 (2.8-22.9) mg. There was no significant change over the 3 years in BMD at the lumbar spine (1.161+/-0.122 vs. 1.169+/-0.022; p = 0.39) or femoral neck (0.944+/-0.023 vs. 0.955+/-0.020; p = 0.47) for the group as a whole, or when subjects were divided according to corticosteroid exposure. However, in the corticosteroid exposed subgroup, patients treated with > or = 7.5 mg/day (n = 14) lost lumbar spine BMD (-0.50%/yr) in contrast to those receiving <7.5 mg/day, who gained 1.06%/yr (p = 0.02). Furthermore, no participant receiving <7.5 mg/day lost lumbar spine BMD, while 57% of patients receiving > or =7.5 mg/day lost lumbar spine BMD (p = 0.01). In the corticosteroid exposed subgroup only, subjects who did not exercise regularly lost femoral neck BMD, while those who did gained femoral neck BMD ( 0.54%/yr vs. 1.39%/yr; p = 0.02). Disease related variables (disease severity, activity, duration, functional capacity) and baseline urinary collagen crosslink levels were not predictive of BMD change. CONCLUSION: Loss of lumbar spine and femoral neck BMD in this premenopausal female SLE population was minimal for the group as a whole; however, a daily dose of prednisolone of > or =7.5 mg was associated with loss of lumbar spine BMD. In corticosteroid exposed patients, regular exercise was protective of femoral neck BMD loss. A single baseline measurement of urinary collagen crosslinks was not predictive of bone loss. PMID- 9972965 TI - Correlation of serum measures of nitric oxide production with lupus disease activity. AB - OBJECTIVE: To determine whether serum measures of nitric oxide production correlate with disease activity in patients with systemic lupus erythematosus (SLE). METHODS: We assayed the levels of serum nitrate/nitrite from 26 patients with SLE followed for 1-3 years and nitrotyrosine levels in sera from 28 additional patients with SLE; sera from 19 controls were tested in both assays. Lupus disease activity was determined via the physician's global assessment, the Lupus Activity Index, and the SLE Disease Activity Index (SLEDAI) at the time of serum collection for the initial set of 26 patients. Statistical correlations were determined using the Wilcoxon rank sum method and one-way ANOVA testing. RESULTS: Serum levels of nitrate/nitrite were significantly higher in 26 patients with SLE compared to 19 controls (SLE, mean 29.5 microM/ml, range 1-438; controls, mean 9.6 microM/ml, range 0-51; p = 0.0004). Overall, there was a significant correlation between serum nitrate/nitrite levels and SLEDAI scores (p = 0.0065). Renal variables within the SLEDAI had the highest correlation with serum nitrate/nitrite (p = 0.0028). Serum nitrotyrosine levels were also significantly higher in patients with SLE versus controls (p = 0.007) and in active SLE versus those with inactive SLE (p = 0.008). CONCLUSION: Serum nitrate/nitrite levels correlated with SLE disease activity, especially nephritis, in the majority of patients studied. Serum nitrotyrosine levels also differentiated controls from patients with lupus and patients with active from those with inactive disease. Due to the ease and low cost of these assays, serum measures of nitric oxide production appear a potentially useful adjunctive laboratory measure of disease activity in SLE and further implicate nitric oxide as an important mediator of disease in SLE. PMID- 9972966 TI - The cholesterol lowering effect of antimalarial drugs is enhanced in patients with lupus taking corticosteroid drugs. AB - OBJECTIVE: To examine the relationship between antimalarial therapy and total cholesterol in patients with systemic lupus erythematosus (SLE) with or without steroid therapy. METHODS: Retrospective study for the University of Toronto Lupus Clinic database between 1976 and 1997. The effects of antimalarials on random total cholesterol levels were assessed in the following situations: patients not receiving steroids (part I) that either initiated or discontinued antimalarials; patients receiving steroids (part II) that were either on a stable dose or initiating antimalarials; and patients initiating steroids with or without antimalarials (part III). Paired t test, Fisher's exact test, and 2 way analysis of variance were used when appropriate. RESULTS: Initiation of antimalarials reduced the baseline total cholesterol by 4.1 % at 3 months in 53 patients (p = 0.020) and by 0.6% at 6 months in 30 patients (p = NS), while the cessation of antimalarials increased the total cholesterol by 3.6% at 3 months in 38 patients (p = NS) and 5.4% at 6 months in 22 patients (p = NS). In 181 patients taking steroids and antimalarials, the mean total cholesterol was 11% less than for 201 patients receiving a comparable dose of steroids alone (p = 0.0023). Initiation of antimalarials on a stable dose of steroids reduced the total cholesterol by 11.3% at 3 months in 29 patients (p = 0.0002) and 9.4% at 6 months in 20 patients (p = 0.004). For patients initiating steroids, the percentage increase in cholesterol was lower in those taking antimalarials compared to patients without antimalarial therapy (p = 0.0149). CONCLUSION: Antimalarials lower total cholesterol in patients receiving steroids and may minimize steroid induced hypercholesterolemia. PMID- 9972967 TI - Anti-DNA and anti-nucleosome antibody affinity--a mirror image of lupus nephritis? AB - OBJECTIVE: To measure relative functional affinities of both IgG anti-DNA and anti-nucleosome antibodies in patients with systemic lupus erythematosus (SLE). METHODS: Serum IgG anti-DNA antibodies were affinity purified from DNA-Sepharose columns (APAD) and tested for functional affinities using dissociation of antigen antibody binding with diethylamine. IgG antibody affinities for nucleosomes prepared from chicken erythrocyte nuclei and apoptotic normal human leukocyte nuclei were also measured. RESULTS: Many patients with SLE nephritis showed low IgG anti-DNA antibody affinity for both DNA and nucleosomes during clinical phases of active nephritis. Serial studies confirmed an apparent relationship between clinical bouts of active renal disease and low residual serum anti-DNA and sometimes anti-nucleosome affinity. Serial studies of patients with SLE without renal disease did not show episodes of low affinity serum anti-DNA. When APAD were compared to renal biopsy eluates, much higher affinity for DNA was found in renal eluates than in APAD in serum. Similarly, low affinity antibodies in serum were associated with high affinity anti-nucleosome antibody in renal biopsy eluates in some but not all of 10 patients with SLE studied. CONCLUSION: Residual IgG anti-DNA antibody affinity for DNA is often low during phases of active SLE nephritis. When nephritis improves or precipitates chronic renal failure, serum anti-DNA antibody affinity increases. Measurement of anti-DNA antibody affinity may provide a useful indicator of renal disease activity. PMID- 9972968 TI - Discrepant expression of neprilysin on fibroblasts in diffuse systemic sclerosis. AB - OBJECTIVE: Neprilysin (NEP; EC3.4.24.11) is an ectopeptidase mainly produced by fibroblasts and cleaving a large number of neuropeptides. We previously found increased plasma circulating levels of NEP in patients with systemic sclerosis (SSc), but in SSc fibroblasts derived from the diffuse subset NEP was present in lower concentration. We evaluate in vitro fibroblasts of both subsets of the disease, diffuse and limited, the intracellular levels of NEP, and its expression as CD10 on the cellular surface. METHODS: Fibroblasts, derived from biopsies taken from affected skin of 8 patients with the limited subset and 5 with the diffuse subset, were grown in vitro and intracellular levels of NEP activity were measured with a fluorometric method, while CD10 surface expression was evaluated by FACS analysis. Cell proliferation was assessed by 3HThymidine incorporation. RESULTS: Intracellular NEP activity was significantly increased in diffuse (7.02+/-4.8 pg/ml/min 10(6) cells) compared to limited SSc (1.11+/-2.0) and control fibroblasts (1.41+/-0.9). CD10 expression was significantly impaired on diffuse SSc fibroblasts (47.3+/-15%) compared to controls (74.6+/-11%) and the limited subset (82.7+/-11%). Cell proliferation of diffuse SSc fibroblasts was strikingly higher than controls and limited SSc fibroblasts. CONCLUSION: These results confirm that NEP is produced by fibroblasts and indicate that in diffuse SSc fibroblasts NEP is produced in higher quantities, while the expression of the enzyme on the cell surface is significantly reduced. This condition may affect the proliferation rate of fibroblasts as well as the metabolism of various peptides. PMID- 9972969 TI - A pilot study: use of fludarabine for refractory dermatomyositis and polymyositis, and examination of endpoint measures. AB - OBJECTIVE: To study the effects of the adenine analog, fludarabine, on patients with refractory dermatomyositis and polymyositis, and to assess variables used in following myositis patients during medical intervention. METHODS: Patients whose myositis was not controlled by prednisone and at least one other immunosuppressive medication were entered into a pilot study during which they received 6 monthly cycles of intravenous fludarabine. Patients were assessed at baseline, every other month, and at month 7 for primary outcome measures of strength and function. Other measurements including peripheral blood cell subsets, muscle enzymes, and various assessments of disease activity were followed monthly during the fludarabine infusion period and for up to 6 months post therapy. RESULTS: Of 16 patients who entered the study, 4 patients were classified as improved, and 7 patients were classified as unchanged. Five patients who withdrew before month 7 were classified as treatment failures. Fludarabine caused a significant and prolonged lymphopenia without an increase in infectious complications over that seen with other immunosuppressive agents used for myositis. A sudden death of one patient at the end of the study was not thought to be drug related. Variables followed during the study emphasized the distinction between patient functional improvement and disease remission. CONCLUSION: A subset of patients with refractory myositis may benefit from fludarabine therapy and controlled trials are indicated. Refinement and validation of variables useful for following myositis patients await larger studies. PMID- 9972970 TI - Giant cell arteritis, polymyalgia rheumatica, and viral hypotheses: a multicenter, prospective case-control study. Groupe de Recherche sur l'Arterite a Cellules Geantes. AB - OBJECTIVE: Although suspected, a viral etiology has never been proven in giant cell arteritis (GCA). We tested for viruses known to induce multinucleated giant cells in human pathology, which include the parainfluenza viruses (HPIV), respiratory syncytial virus, measles virus, herpesviruses type 1 and 2, and the Epstein-Barr virus. METHODS: A multicenter case-control study on incident cases of temporal arteritis (TA) and polymyalgia rheumatica (PMR). Population based age and sex matched controls were randomly selected. Serological tests for IgG and IgM directed against the viruses listed above were performed, on blood samples taken at the time of clinical diagnosis. RESULTS: Three hundred five new patients were included over a 5 year period, of whom 159 presented with positive biopsy TA, 70 with negative biopsy TA, and 76 with negative biopsy PMR. Thirty-eight percent of cases versus 20.9% of controls were positive for IgM directed against HPIV (p = 0.00005). The association was stronger in the positive TA subgroup [positivity rate 43.31%; odds ratio with controls 2.89 (95% CI 1.82-4.60, p = 0.000006)] than in the PMR or negative biopsy TA subgroups. Only HPIV type 1 was associated with the disease, regardless of the season or the geographical origin of the cases. Positivity rates for HPIV types 2 and 3 and for the other viruses tested were similar in cases and controls. CONCLUSION: Our findings suggest that reinfection with HPIV type 1 is associated with the onset of GCA in a subset of patients, particularly in cases with positive TA biopsy. PMID- 9972971 TI - Hepatitis C virus infection: prevalence in psoriasis and psoriatic arthritis. AB - OBJECTIVE: To study the prevalence of hepatitis C virus (HCV) infection in 2 groups of patients, one group with psoriasis and the other with psoriatic arthritis (PsA). METHODS: We detected anti-HCV antibodies by ELISA and by a recombinant immunoblot assay (RIBA) in the sera of 50 patients with psoriasis and 50 with PsA. As controls we used a group of 76 patients with rheumatoid arthritis (RA), and referred to data on the prevalence of HCV in the general Italian population. RESULTS: By ELISA, anti-HCV antibodies were detected in 6/50 (12%) patients with PsA, in 5/50 (10%) patients with psoriasis, and in 4/76 (5.2%) patients with RA. All the reactive PsA and RA sera also tested positive on RIBA, while only 3 of the 5 positive results for sera of patients with psoriasis were confirmed by RIBA. The prevalence of HCV infection in patients with psoriasis was not significantly higher than in controls. In contrast, the rate of HCV infection observed in the 50 patients with PsA was higher than that in the other groups, the difference being statistically significant between patients with PsA and the general population. CONCLUSION: Our data do not support the hypothesis that HCV infection may play a role in the pathogenesis of psoriasis. On the other hand they show a statistically significant difference between the prevalence of HCV infection in patients with PsA and the general population. PMID- 9972972 TI - Corticosteroid sparing effect of low dose methotrexate treatment in adult Still's disease. AB - OBJECTIVE: Adult Still's disease (ASD) is a rare chronic polyarthritis, usually treated with corticosteroid therapy. Because some patients become dependent on high dose prednisone or are refractory to that treatment, and because adverse events are frequent with corticosteroid, we evaluated the efficacy of low dose methotrexate (MTX) as a second-line drug. METHODS: We retrospectively studied 26 patients with ASD treated with low dose MTX because their disease was either resistant to or dependent on corticosteroids. RESULTS: The group included 13 women and 13 men, with a mean age of 32.6 years at onset of ASD. Mean disease duration at the beginning of MTX treatment was 59.9 mo (range 7 to 444). Evaluation took place at the maximum followup, which averaged 48.9 mo (range 8 to 136). The mean dose of MTX was 11.5+/-3.6 mg/week (range 7.5 to 17.5). Twenty three patients responded to MTX; 18 had complete remission. No difference was seen between patients with or without extraarticular manifestations. Leukocyte and neutrophil counts and erythrocyte sedimentation rate were significantly reduced (p = 0.0001). Daily prednisone intake decreased by 69% (21.5 mg) (p = 0.0001). Eleven patients were able to stop taking corticosteroids. One patient with AA amyloidosis renal failure died of neutropenia: this was the only serious adverse event. CONCLUSION: MTX is an effective second-line treatment of ASD that does not respond to prednisone. It allows significant reduction of corticosteroid doses, which is beneficial to these patients, who have frequent and numerous corticosteroid related adverse events. PMID- 9972973 TI - Uremic tumoral calcinosis in patients receiving longterm hemodialysis therapy. AB - OBJECTIVE: To analyze a series of uremic tumoral calcinosis (UTC) in patients receiving longterm dialysis therapy. METHODS: Twelve patients receiving longterm hemodialysis affected by tumoral calcinosis were analyzed. Clinical, radiological, and pathological features were evaluated and pathogenic factors were reviewed. RESULTS: The most common sites for UTC were the elbow, hip, hand, and wrist. The lesions were multiple (67%, n = 8), of large size, and symptomatic with joint mobility impairment (75%, n = 9) as well as nerve compression (33%, n = 4). High serum calcium and phosphate concentrations were detected in 50% (n = 6) and 100% of the patients, respectively. An increased calcium-phosphorus product (Ca x P) was observed in all patients, either due to overt secondary hyperparathyroidism (42%, n = 5), or secondary to iatrogenic hypercalcemia and/or severe hyperphosphoremia of multifactorial etiology (i.e., prolonged and excessive administration of calcitriol and calcium carbonate, insufficient dialysis and inadequate phosphorus chelating therapy, etc.) (58%, n = 7). Several treatment strategies were followed (surgical excision, parathyroidectomy, renal transplant) in combination with aggressive medical therapy to decrease Ca x P product, achieving complete remission in 83% of the patients. CONCLUSION: UTC lesions show clinical and pathogenic features that differ from those of idiopathic tumoral calcinosis. The most important pathogenic factor involved in UTC is an increase in Ca x P, not necessarily related to hyperparathyroidism. Combined treatment strategies allow complete remission in a high proportion of patients. A low Ca x P is necessary to prevent development of UTC. PMID- 9972974 TI - Presence and distribution of collagen II, collagen I, fibronectin, and tenascin in rabbit normal and osteoarthritic cartilage. AB - OBJECTIVE: To investigate changes in the composition of articular cartilage matrix during the development of experimental osteoarthritis (OA), collagen type II, collagen type I, and the noncollagenous proteins fibronectin and tenascin were studied in normal and osteoarthritic cartilage of rabbits. METHODS: OA of the knee joint was induced by a medial meniscectomy and section of the medial collateral ligament and anterior cruciate ligament. Frozen sections of rabbit normal and OA cartilage were stained with monoclonal antibodies against collagen type II, collagen type I, fibronectin, and tenascin. RESULTS: Collagen II manifested a decreased interterritorial staining and seemed to increase territorially in the deeper zones of the OA cartilage. Collagen I was found in normal cartilage as a thin layer covering the surface and also in OA fibrillated cartilage. Fibronectin was present in normal and OA cartilage. Whereas a layer covered the normal cartilage, a thicker layer was observed in OA cartilage. In addition, changes in fibronectin distribution from the pericellular to the interterritorial matrix were observed. Tenascin was also found in normal cartilage matrix, particularly in the territorial and interterritorial matrix of the deeper zones. It showed an increased staining intensity in fibrillated cartilage, in the pericellular matrix of the upper chondrocytes, and on the surface lining in OA cartilage. CONCLUSION: Collagen type II deposition seems to increase in the deeper cartilage zones during the osteoarthritic process, as a sign of tissue repair response. Collagen type I, fibronectin, and tenascin show enhanced deposition in the upper, fibrillated osteoarthritic cartilage, suggesting a common mediator controlled pathway. PMID- 9972975 TI - Thyroid hormones induce features of the hypertrophic phenotype and stimulate correlates of CPPD crystal formation in articular chondrocytes. AB - OBJECTIVE: Articular cartilage affected by calcium pyrophosphate dihydrate (CPPD) crystal deposition contains abnormal chondrocytes with morphologic similarities to the terminally differentiated hypertrophic chondrocytes that mineralize in growth plate cartilage. These chondrocytes also elaborate high levels of extracellular inorganic pyrophosphate (PPi), an essential component of the CPPD crystal. Several factors that stimulate articular chondrocyte PPi elaboration also induce terminal differentiation in growth plate chondrocytes. We hypothesized that factors such as thyroid hormones (T3 and T4) that are potent stimulants of growth plate chondrocyte hypertrophy might also stimulate articular chondrocyte hypertrophic differentiation. We also hypothesized that like transforming growth factor-beta (TGF-beta), ascorbate, and retinoic acid, thyroid hormones would increase chondrocyte PPi elaboration. METHODS: We determined the effects of T3, T4, and TGF-beta on markers of the hypertrophic phenotype such as alkaline phosphatase (ALPase) activity and type X collagen production; and the effects of T3 and T4 on processes implicated in CPPD crystal formation including PPi elaboration and nucleoside triphosphate pyrophosphohydrolase (NTPPPH) activity in adult porcine articular chondrocytes in culture. RESULTS: ALPase activity increased 3-fold with T3 and T4 and 1.3-fold with TGF-beta. Type X collagen levels also increased with thyroid hormone treatment. [125I]T3 binding studies proved the existence of saturable T3 receptors on chondrocytes. Media [PPi] and cellular NTPPPH activity significantly increased in cultures treated with 1-10 nM T3 or 100-500 nM T4. CONCLUSION: Increased PPi elaboration is an additional and previously unrecognized feature of hypertrophic differentiation in articular chondrocytes. These terminally differentiated chondrocytes may play a pathogenic role in CPPD crystal deposition disease. PMID- 9972976 TI - Antipolymer antibody reactivity in a subset of patients with fibromyalgia correlates with severity. AB - OBJECTIVE: To determine the prevalence of antipolymer antibodies (APA) in patients with fibromyalgia (FM) and autoimmune disease control groups and to determine if the presence of these antibodies correlates with severity in patients with FM. METHODS: Sera from patients with FM (n = 47), osteoarthritis (OA) (n = 16), and rheumatoid arthritis (RA) (n = 13) were analyzed. Patients with implants of any kind and patients with concurrent autoimmune conditions were excluded from study. Banked sera from autoimmune disease controls including poly/dermatomyosis (n = 15), RA (n = 30), systemic lupus erythmatosus (SLE) (n = 30), and systemic sclerosis (SSc) (n = 30) were also analyzed. To determine if seroreactivity correlates with severity, banked sera from patients with FM assessed as severe (n = 28) or mild (n = 37) and from controls (n = 21) were assayed. RESULTS: Following analysis, the prevalence of seroreactivity was found to be higher in patients with FM (22/47, 47%) compared to patients with OA (3/16, 19%; p<0.1) or RA (1/13, 8%; p<0.05) and the autoimmune disease control sera from poly/dermatomyosis (2/15, 13%; p<0.05), and patients with RA (3/30, 10%; p<0.01), SLE (1/30, 3%; p<0.01), and SSc (1/30, 3%; p<0.01). The prevalence of APA seroreactivity was also significantly higher in patients with severe FM (17/28, 61%) compared to patients with mild FM (11/37, 30%; p<0.05) and controls (4/21, 19%; p<0.01). In addition, both mean threshold and mean tolerance dolorimetry scores were significantly lower in the seropositive patients with mild FM (1.33+/ 0.21, 1.95+/-0.25, respectively) compared to the seronegative patients (1.83+/ 0.08, 2.53+/-0.11; p<0.05 for both comparisons, respectively). CONCLUSION: These results reveal that an immunological response, production of anti-polymer antibodies, is associated with a subset of patients with FM. The results also suggest that the APA assay may be an objective marker in the diagnosis and assessment of FM and may provide additional avenues of investigation into the pathophysiological processes involved in FM. PMID- 9972977 TI - Genetic linkage analysis of multicase families with fibromyalgia syndrome. AB - OBJECTIVE: Based on the reports of familial aggregation of fibromyalgia (FM) syndrome, we investigated its possible genetic linkage to HLA by studying multicase families. METHODS: Forty Caucasian multicase families with a diagnosis of FM (American College of Rheumatology criteria) in 2 or more first degree relatives were investigated. Eighty-five affected and 21 unaffected members of 41 sibships were studied. Depression symptomology was assessed by Zung Self-rating Depression Scale (SDS). HLA typing was performed for A, B, and DRB 1 alleles, and haplotypes were determined with no knowledge of the subject's diagnosis. We investigated genetic linkage to the HLA region by evaluating sibships in multicase families. RESULTS: Sibship analysis showed significant genetic linkage of FM to the HLA region (p = 0.028). Subgroup analysis was also performed for 17 families where the proband was also noted to have depression (with an SDS index value > or =60). We found that the presence of depression did not influence the observed results (p = 0.22). CONCLUSION: . Our study of 40 multicase families confirms existence of a possible gene for FM that is linked with the HLA region. Our results should be regarded as preliminary and their independent confirmation by other studies is warranted. PMID- 9972978 TI - Chronic widespread pain in the community: the influence of psychological symptoms and mental disorder on healthcare seeking behavior. AB - OBJECTIVE: To determine whether psychological symptoms and mental disorder are an intrinsic part of the chronic widespread pain syndrome or whether they have been observed in clinic attenders primarily because of their influence on the decision to seek a medical consultation. METHODS: A population survey of 1953 subjects was conducted in the Greater Manchester area of the United Kingdom. The survey included a postal questionnaire, and in a subgroup of respondents with high levels of distress, the presence of mental disorder was assessed by a semistructured standardized interview. Subjects with chronic widespread pain were classified according to whether they had sought a medical consultation for the reported pain ("consulters") or not ("nonconsulters"). RESULTS: In all, 252 subjects (13%) satisfied American College of Rheumatology criteria for chronic widespread pain, and of these 72% reported having consulted a general practitioner about this pain. There was a clear difference in levels of psychological distress, measured by the General Health Questionnaire (GHQ), between consulters, nonconsulters, and those with no pain. Consulters did not differ from nonconsulters in terms of levels of fatigue, social dysfunction, or number of somatic symptoms reported. Although consulters (among whom one in 4 had a mental disorder) were more likely to have a mental disorder than subjects without pain [OR = 4.9, 95% CI (2.6, 9.5)] the increase in risk comparing consulters to nonconsulters [OR = 2.1, 95% CI (0.7, 5.9)] and nonconsulters to subjects without pain [OR = 1.4, 95% CI (0.7, 2.6)] was not significant. CONCLUSION: The results suggest that psychological distress is associated with chronic widespread pain in addition to any effect on whether consultation is sought for symptoms. The finding that one-quarter of consulters to primary care with chronic widespread pain have a mental disorder should alert primary care physicians and rheumatologists to screen for mental disorder in this group. PMID- 9972979 TI - Arthritis in patients with chronic hepatitis C virus infection. AB - OBJECTIVE: To describe the clinical picture of arthritis in patients with chronic infection by hepatitis C virus (HCV). METHODS: Two patient populations were studied. Patients with arthritis and evidence of serum elevation of alanine aminotransferase (ALT) at the consultation were checked for HCV infection. A second group of 303 consecutive patients with rheumatoid arthritis (RA) were also checked for the presence of HCV antibodies. All patients attended the outpatient rheumatology unit of a tertiary care teaching hospital. Chronic HCV infection was determined by the presence of viral RNA in serum. A group of 315 first-time blood donors served as controls. RESULTS: Twenty-eight patients with arthritis and chronic HCV infection were identified. Seven fulfilled criteria for RA, psoriatic arthritis was found in one patient, systemic lupus erythematosus in one, gout in 2, chondrocalcinosis in 2, osteoarthritis in 7, and tenosynovitis in one. In 7 patients with a clinical picture of intermittent arthritis, a definitive diagnosis could not be made. In these patients, mixed cryoglobulinemia was present in 6/7 (86%), whereas mixed cryoglobulinemia was found in 6/21 (28%) of the other patients. Among patients with RA, 23 (7.6%) had HCV antibodies, and active infection by HCV was found in 7 (2.3%) patients. The prevalence of HCV antibodies in a blood donor population was 0.95%, significantly different (p<0.001; 95% CI 0.03, 0.10) compared to patients with RA. The distribution of antibodies determined by recombinant immunoblot analysis was similar (p = NS) between RA patients and blood donors with HCV antibodies. CONCLUSION: There is not a single clinical picture of arthritis in patients with chronic HCV infection. There is a well defined picture of arthritis associated with the presence of mixed cryoglobulinemia that consists of an intermittent, mono or oligoarticular, nondestructive arthritis affecting large and medium size joints. Although a high prevalence of HCV antibodies is suspected in patients with RA, its occurrence may be coincidental and its interpretation is difficult to determine from the data in this study. PMID- 9972980 TI - Interleukin 8 and monocyte chemoattractant protein-1 in patients with juvenile rheumatoid arthritis. Relation to onset types, disease activity, and synovial fluid leukocytes. AB - OBJECTIVE: To measure serum and synovial fluid (SF) levels of interleukin 8 (IL 8) and monocyte chemoattractant protein-1 (MCP-1) in patients with juvenile rheumatoid arthritis (JRA) and to compare them with adult rheumatoid factor positive rheumatoid arthritis (RA). METHODS: IL-8 and MCP-1 were measured by immunoassay (1) in sera obtained from 55 children with JRA and from 16 adults with RA, and (2) in SF obtained from 30 children with JRA and 11 adults with RA. RESULTS: Patients with active systemic JRA had serum levels of IL-8 and MCP-1 higher than in controls (p<0.01) and in patients with active polyarticular or pauciarticular JRA (p<0.05). In patients with RA serum MCP-1 levels were higher than in patients with the 3 JRA onset types, while no difference was found for IL 8 levels. Patients with systemic JRA and with current systemic features had serum levels of IL-8 and MCP-1 higher (p = 0.03 and p = 0.04, respectively) than patients in which systemic features had subsided. No significant differences in SF IL-8 or MCP-1 levels were found among the 3 JRA onset types or adults with RA. In patients with JRA SF leukocyte counts were correlated with SF IL-8 levels (p = 0.002), but not with MCP-1 levels. Moreover, SF levels of both IL-8 and MCP-1 were correlated with those of IL-1beta (p<0.001) and IL-6 (p<0.01), but not with those of TNF-alpha. CONCLUSION: Elevated serum levels of IL-8 and MCP-1 in patients with systemic JRA with current systemic features at sampling suggest systemic production of the 2 chemokines during systemic phases of the disease. Similar SF levels of IL-8 and MCP-1 among the 3 JRA onset-types and RA suggest comparable local production of the 2 chemokines. PMID- 9972982 TI - Sweet's syndrome with arthritis in an 8-month-old boy. AB - Sweet's syndrome was diagnosed in a 4-month-old boy. He was successfully treated with systemic corticosteroids. At the age of 8 months, he developed acute arthritis in his right knee. The synovial fluid was analyzed and revealed a very high neutrophil count and neutrophil activation with a detectable level of intraarticular granulocyte-monocyte colony stimulating factor (GM-CSF). Prednisone injection into the knee led to dramatic improvement. No recurrence occurred. Although arthritis and/or arthralgia are common features in adult patients with Sweet's syndrome, this is the first reported case of Sweet's arthritis in a child. PMID- 9972981 TI - Favorable response to intravenous methylprednisolone and cyclophosphamide in children with severe neuropsychiatric lupus. AB - OBJECTIVE: To evaluate the effect of intravenous methylprednisolone (IVMP) and cyclophosphamide (IVCy) in children with severe neuropsychiatric (NP) systemic lupus erythematosus (NPSLE). METHODS: We studied 7 consecutive pediatric patients with severe NPSLE. All patients were treated initially with IVMP and IVCy followed by monthly IVCy for at least 3 months, and then every 2 and/or 3 months according to clinical response. Prednisone was given at 1-2 mg/kg during the first month. Laboratory studies included routine laboratory tests, antinuclear antibodies, anti-dsDNA, antiphospholipid antibodies, and complement components C3 and C4. Neurodiagnostic studies included cerebrospinal fluid, magnetic resonance imaging, computed tomography scanning, single photon emission computed tomography and electroencephalography. RESULTS: Three patients had organic brain syndrome with psychosis, 3 had seizures, 1 stroke, 1 cerebral vasculitis, 1 optic neuritis, and 1 transverse myelitis. In 3 of these cases, nervous system involvement was the initial presentation of SLE. Five patients had 2 or more NP manifestations. Most of them were accompanied by general SLE activity. Anticardiolipin antibodies were positive in 3 patients and none was anticoagulated. All patients improved, 6 patients had a complete recovery and 1 patient recovered with minor neurological deficit. All but one improved significantly within the first week of combined IVMP and IVCy. The mean time of follow-up was 37 months (range 8-55). IVCy was well tolerated with minimal side effects. CONCLUSION: Early aggressive treatment with combined IVMP and IVCy followed by monthly IVCy may be an effective therapy for severe NPSLE in children. PMID- 9972983 TI - Henoch-Schonlein purpura associated with Toxocara canis infection. AB - We describe a case of Henoch-Schonlein purpura in the onset of Toxocara canis infection. The diagnosis was made in a 17-year-old boy based on the association of palpable purpura, oligoarthritis, acute abdominal pain, microhematuria, and cutaneous vasculitis. Toxocariasis, suggested by hypereosinophilia and domestic contact with a puppy, was confirmed by anti-Toxocara IgG and IgE and Western blot. Complete spontaneous resolution occurred within a few days. Transient presence of antinuclear antibodies and the absence of larvae in the skin biopsy favor an immunologic parasite induced disorder. A hypersensitivity vasculitis to Toxocara canis is suggested. PMID- 9972984 TI - Longitudinal involvement of the spinal cord in a patient with lupus related transverse myelitis. AB - Transverse myelitis is a rare and serious complication of systemic lupus erythematosus (SLE). Magnetic resonance imaging is the investigation of choice for diagnosis and followup. This typically shows T1 and T2 signal prolongation, cord widening, and contrast enhancement over several spinal segments. We describe a 21-year-old woman with SLE who developed very extensive SLE related transverse myelitis with longitudinal involvement of the spinal cord from C3 to T2 and from T7 to the conus medullaris. Clinically, this was manifest as leg weakness, bladder dysfunction, severe low back pain, and patchy lower limb sensory loss. She responded to treatment with pulse cyclophosphamide and high dose corticosteroids with complete recovery in 3 months. To our knowledge, this is the first case report of such an extensive "longitudinal" myelitis. PMID- 9972985 TI - Takayasu's arteritis involving proximal pulmonary arteries and mimicking thromboembolic disease. AB - The pulmonary manifestations of Takayasu's arteritis (TA) are frequently overshadowed by the systemic circulation involvement. We describe a patient who presented with life threatening complications of unrecognized proximal pulmonary arterial disease that mimicked thromboembolic disease. We review the literature on pulmonary involvement in TA, and discuss the use of imaging studies in this disease. PMID- 9972986 TI - Dieulafoy's lesion of the esophagus as a probable complication of Takayasu's arteritis. AB - Dieulafoy's lesion is an abnormal submucosal artery in the gastrointestinal tract characterized by massive gastrointestinal bleeding. We describe a patient who developed Dieulafoy's lesion of the esophagus in the course of isolated pulmonary Takayasu's arteritis. Angiographic findings indicated a relationship between pulmonary arterial involvement of Takayasu's disease and Dieulafoy's lesion of the esophagus. This observation represents the first report of the association between Takayasu's arteritis and Dieulafoy's lesion of the esophagus. PMID- 9972987 TI - Wegener's granulomatosis presenting with a renal mass. AB - Wegener's granulomatosis (WG) is a systemic disease characterized by necrotizing granulomatous vasculitis that involves primarily the upper and lower respiratory tracts and, in most cases, the kidneys. Kidney involvement in WG presenting as a mass is recognized, but is very rare. We describe a case of WG presenting with upper and lower respiratory symptoms and a renal mass due to both WG and renal cell carcinoma. PMID- 9972988 TI - Longitudinal and observational studies module. PMID- 9972989 TI - Critical issues in longitudinal and observational studies: purpose, short versus long term, selection of study instruments, methods, outcomes, and biases. AB - Longitudinal observational studies (LOS) provide key information about outcomes and treatment effectiveness that are not available from other types of investigations, including randomized controlled trials. Although LOS are easy to perform, they are difficult to perform correctly. Major problems include recruitment, retention, and relevance, but the central problems in LOS are bias, understanding the nature of the biases, and reporting the biases. To advance the quality and validity of LOS there must be a uniform requirement for reporting detailed data that includes details about the sampled population and the sampling methods, the rationale for the selection of control subjects, the probable biases, and estimates of the extent and consequences of the biases. Sufficient covariates should be collected so that where possible statistical adjustment for bias can be made. PMID- 9972991 TI - Reporting requirements for longitudinal observational studies in rheumatology. PMID- 9972990 TI - A proposed 30-45 minute 4 page standard protocol to evaluate rheumatoid arthritis (SPERA) that includes measures of inflammatory activity, joint damage, and longterm outcomes. AB - A proposed 4 page, 30-45 minute standard protocol to assess rheumatoid arthritis (SPERA) is described that includes all relevant measures of inflammatory activity such as joint swelling, measures of joint damage such as joint deformity, and outcomes such as joint replacement surgery, to monitor patients in longterm observational studies. Forms are included: (1) a patient self-report modified health assessment questionnaire (MHAQ) to assess function, pain, fatigue, psychological distress, symptoms, and drugs used; (2) assessor-completed forms: "RA clinical features" --criteria for RA, functional class, family history, extraarticular disease, comorbidities, joint surgery, radiographic score, and laboratory findings. (3) A 32 joint count with 5 variables: (a) a "shorthand" normal/abnormal so that normal joints require no further detailed assessment; (b) tenderness or pain on motion; (c) swelling; (d) limited motion or deformity; (e) previous surgeries; physical measures of function, i.e., grip strength, walk time, and button test. (4) Medication review of previous disease modifying antirheumatic drugs (DMARD), work history, and years of education. The forms allow cost effective acquisition of all relevant measures of activity, damage, and outcomes in routine clinical care, and allow recognition that measures of activity may show similar or improved values over 5-10 years, while measures of damage and outcomes indicate severe progression in the same patients. The SPERA is feasible to acquire most known relevant measures of activity, damage, and outcomes in RA in 30-45 min in usual clinical settings, to provide a complete database for analyses of longterm outcomes. PMID- 9972992 TI - Preliminary core set of domains and reporting requirements for longitudinal observational studies in rheumatology. AB - Observational and longitudinal observational studies (LOS) provide essential information about the course and outcome of rheumatic disorders that cannot be provided by randomized controlled trials, and they constitute the major clinical scientific communication in rheumatology. There has been no consensus as to the full and appropriate content of LOS. This report defines a core set of domains and reporting requirements for LOS. At the 1998 OMERACT IV Conference a consensus process evaluated the literature of rheumatology in light of the constructs, variables, and outcomes of rheumatology by using introductory lectures, nominal groups, and plenary sessions. The result of this process was to identify 5 "core" domains that should be included in every LOS: Health Status, Disease Process, Damage, Mortality, and Toxicity/Adverse Reactions. Two additional domains, Work Disability and Costs, were recognized as important, but need not be used in all LOS. Eleven subdomains were identified that divided the domains into convenient clinical and conceptual units. A set of reporting requirements was also determined. The core recommendations, which follow on the WHO ICIDH-2 outline, are not disease-specific; the substitution of different "disease process" and "damage" measures make them suitable for many rheumatic disorders. The core set is intended to serve as a core for LOS in almost all rheumatic conditions. PMID- 9972993 TI - Outcome measures to be used in clinical trials in systemic lupus erythematosus. AB - The optimal outcome measures to be employed in clinical trials of systemic lupus erythematosus (SLE) have yet to be determined. Useful instruments should assess disease outcome in terms of all organ system involvement, as well as measures important to the patient. This article reviews those outcome measures that have been utilized in cohort studies in SLE, as well as their limited use in randomized clinical trials (RCT). Six disease activity measures have been developed: British Isles Lupus Assessment Group Scale (BILAG), European Consensus Lupus Activity Measure (ECLAM), Lupus Activity Index (LAI), National Institutes of Health SLE Index Score (SIS), Systemic Lupus Activity Measure (SLAM), and Systemic Lupus Erythematosus Disease Activity Index (SLEDAI). They have been validated in cohort studies as reflecting change in disease activity, and against each other. RCT utilizing SLAM, SLEDAI, BILAG, ECLAM, SIS, SLAM, SLEDAI are ongoing. It is recommended that the disease activity index of choice be selected; but simultaneous computer generation of multiple indices will facilitate comparisons across therapeutic interventions. A damage index has been developed and validated as the Systemic Lupus International Cooperating Clinics (SLICC)/American College of Rheumatology (ACR) Damage Index or SDI. In several cohort studies it has been shown sensitive to change over time, and to reflect cumulative disease activity. There is no health status or disability instrument specific to SLE. The Medical Outcomes Survey (SF-20) captures health status/health related quality of life (HRQOL) better than the Health Assessment Questionnaire (HAQ) in patients with SLE, but does not adequately reflect fatigue. The SF-36 does assess fatigue, and correlates closely with the SF-20. These data indicate that any individual measure of clinical response to a therapeutic intervention in SLE may reflect only a portion of what might be termed the "true outcome." Based on this work, the way is now paved to attempt to develop consensus on the important domains to be measured in clinical trials in SLE, the most appropriate instruments to use and the minimal clinically important differences in their results. PMID- 9972994 TI - Development of a clinical chart to compute different disease activity indices for systemic lupus erythematosus. AB - Between 1990 and 1995 a European Consensus Group carried out a multicenter study to reach agreement of the definition of disease activity in systemic lupus erythematosus (SLE). A new index, the European Consensus Lupus Activity Measurement (ECLAM) index, was developed. In a second phase of the study, a prospective survey aimed at validating ECLAM and 4 other scales as steady-state and transition indices for disease activity in SLE was completed. We present the results of this survey. A standardized clinical chart was developed, together with a computer program that could automatically calculate the ECLAM score, as well as the scores for some of the disease activity scales most widely used at present, i.e., the British Isles Lupus Assessment Group, Systemic Lupus Activity Measure, SLE Disease Activity Index, and the SLE Index Score (SIS). With the participation of 28 centers in 15 different European countries, data from 121 prospectively selected new lupus patients were collected. The validity of the 5 activity scales was assessed by comparing the computed scores for each patient to a gold standard, i.e., the physician's subjective judgment on disease activity measured using a semiquantitative scale. All the indices were found to be valid instruments for measuring disease activity in SLE in both the steady-state and transition phases. The results for the various indices closely correlated with one another. Thus, the computerized chart developed by the European Consensus Group offers a simple and reliable instrument to assess disease activity and could be used to monitor lupus patients both in clinical practice and in clinical trials. PMID- 9972995 TI - Measures of disease activity, damage, and health status: the Hopkins Lupus Cohort experience. PMID- 9972996 TI - Randomized clinical trials and longitudinal observational studies in systemic lupus erythematosus: consensus on a preliminary core set of outcome domains. AB - The OMERACT module on systemic lupus erythematosus (SLE) dealt with the definition of preliminary core sets of outcome domains for randomized clinical trials (RCT) and longitudinal observational studies (LOS). After lectures introducing the problems and addressing the key issues, 6 discussion groups, 3 each for LOS and RCT, discussed and weighted more than a dozen possible items for use as outcome domains. The means of the respective 3 groups were calculated. For both RCT and LOS the same outcome domains received more than 10 of a total maximum of 100 points: disease activity, health related quality of life (HRQOL), damage, and toxicity/adverse events. However, the weights for HRQOL and damage were different for LOS and RCT. A final vote led to the acceptance of these 4 variables as a preliminary core set for outcome in SLE by more than 80% of the participants. This core set will allow for improved design, performance, and evaluation of future studies in SLE. However, a number of domains not included in the core set were regarded as important for further analysis and research. PMID- 9972997 TI - Tophaceous gout mimicking tumoral growth. PMID- 9972998 TI - Antiphospholipid antibody syndrome associated with hepatitis C infection. PMID- 9972999 TI - Serum levels of Th2 cytokines IL-4 and IL-10 in Behcet's disease. PMID- 9973000 TI - Reassessment of mirthful laughter in rheumatoid arthritis. PMID- 9973001 TI - Levels of cadmium in kidney and liver tissues among a Canadian population (province of Quebec). AB - In an exploratory study, levels of cadmium in whole-kidney and liver tissues of 314 subjects from the general population of the province of Quebec (Canada) were measured postmortem. Frequency distributions of cadmium concentrations were lognormal. As reported in similar studies, age and especially smoking habits were the main variables affecting cadmium concentrations. The geometric mean of whole kidney concentrations (wet weight) was 17.62 microg/g, with a minimum concentration of 2.25 microg/g and a maximum of 100.61 microg/g. Mean concentrations of cadmium in kidneys increased with age, reaching a plateau in the group 50 to 59 yr (29.49 microg/g), and falling slowly thereafter. PMID- 9973002 TI - Differential regulation of in vitro cytokine production by human blood cells in response to methylmethacrylate. AB - The effect of methylmethacrylate (MMA) on human whole blood cultures (WBC) obtained from healthy donors was investigated. Lymphocyte transformation and cytokine production, that is, interleukin 6 (IL-6), interferon-gamma (IFN-gamma), and tumor necrosis factor-alpha (TNF-alpha), were used to evaluate the immunological activities of MMA. Primary cytotoxicity testing of MMA in Jurkat cells showed that this compound decreased the cell proliferation to 50% at a concentration of >60 mmol/L. Similarly, MMA significantly decreased lymphocyte transformation in either phytohemagglutinin (PHA) or Staphylococcus aureus protein A (SpA) activated WBC at 100 mmol/L. In contrast to activated WBC, MMA had no observed effect on resting blood cells. Cytokine expression in WBC seemed differentially modulated by MMA. There was a tendency for IL-6 production in both resting and PHA-stimulated WBC to be upregulated, while IL-6 induced in SpA stimulated cultures was downregulated. TNF-alpha was slightly increased by MMA in resting WBC at early incubation periods, and it was slightly downregulated in response to PHA or SpA activation. Suppression of IFN-gamma secretion was observed in WBC with or without PHA or SpA stimulation. The overall results demonstrated that MMA at physiological levels could influence the cytokine production in normal human blood cells in vitro. Alterations of cytokine production patterns by MMA indicate that this compound has multiple regulatory effects on immune reactions in normal human blood. PMID- 9973003 TI - Induction of metallothionein and heme oxygenase in rats after inhalation of endotoxin. AB - Various stress proteins appear to play a role in injury and repair produced by inhaled pollutants. The present study examined the effect of inhaled endotoxin on the expression of the metallothionein and heme oxygenase genes. Rats were exposed to saline or endotoxin aerosols for 3 h and sacrificed up to 3 d following exposure. The significant induction of metallothionein mRNA in both the lung (fourfold increase) and liver (one-fold) were greatest at 3 h and returned to basal levels by 24 h after endotoxin exposure. Similarly, the increase in tissue metallothionein was greater in the lung. In situ hybridization in mice showed large increases in the relative abundance of metallothionein transcripts in epithelial cells of the conducting airways, in surrounding airway tissue, and in the nearby gas exchange region. While an endotoxin-induced significant increase in heme oxygenase mRNA followed a time course similar to that observed for metallo thionein, the relative magnitude was reversed for the lung and liver. Heme oxygenase mRNA was induced greater in the liver (twofold) than in the lung (60% above control). Our findings demonstrate that metallothionein and heme oxygenase are early response genes that are rapidly activated after inhalation of occupationally relevant concentrations of endotoxin. PMID- 9973004 TI - Xenobiotic-metabolizing enzymes in carp (Cyprinus carpio) liver, spleen, and head kidney following experimental Listeria monocytogenes infection. AB - Infection of carp with Listeria monocytogenes 4b resulted in decreased liver, spleen, and head kidney enzyme activities, involved in the metabolism of xenobiotics. After infection, cytochrome P-450 levels and ethoxyresorufin O deethylase (EROD) activity were decreased while conjugation enzymes remained unaffected. The maximum decrease for phase I enzymes occurred on d 3. This loss of monooxygenase levels and activity could not be directly correlated with an increase in the number of organisms, as consistently high bacterial counts were observed in all three organs during infection. The effect of L. monocytogenes infection was also measured in carp exposed to 3-methylcholanthrene (MCA). Cytochrome P-450 levels and EROD activity were significantly reduced, especially on d 3. A significant decreased activity of conjugation enzymes such as glutathione S-transferase (GST) and UDP-glucuronosyltransferase (UDPGT) was also observed for all days studied. Listeria infection inhibited MCA-induced increases in xenobiotic-metabolizing enzyme activities. These results indicate that infection may have deleterious effects on basal cytochrome P-450 monooxygenase levels. Furthermore, MCA treatment aggravates the insult to xenobiotic biotransformation enzymes by L. monocytogenes infection, by impairing a number of detoxification enzymes. These findings could result in significant changes in the susceptibility of fish to pollutants. PMID- 9973005 TI - 50th anniversary historical article. Heart failure. PMID- 9973006 TI - A perspective on the potential problems with aspirin as an antithrombotic agent: a comparison of studies in an animal model with clinical trials. AB - Aspirin is the most widely prescribed agent to reduce the platelet-mediated contributions to atherosclerosis, coronary thrombosis and restenosis after angioplasty. While aspirin treatment has led to significant reductions in morbidity and mortality in many clinical trials, there are several scenarios in which aspirin may fail to provide a full antithrombotic benefit. The cyclic flow model of experimental coronary thrombosis suggests that elevations of plasma catecholamines, high shear forces acting on the platelets in the stenosed lumen and the presence of multiple, input stimuli can activate platelets through different mechanisms that may lead to thrombosis despite aspirin therapy. Aspirin therapy is limited because it only blocks some of the input stimuli, leaving aspirin-independent pathways through which coronary thrombosis can be precipitated. These include thrombin and thrombogenic arterial wall substrates such as tissue factor. New agents that block the adenosine diphosphate (ADP) receptor, or regulate platelet free cytosolic calcium, such as direct nitric oxide donors, may be more potent overall than aspirin. Agents that block the platelet integrin GPIIb-IIIa receptor inhibit the binding of fibrinogen to platelets regardless of which input stimuli activate the platelet and, thus, as demonstrated in the cyclic flow model, would be much more potent than aspirin as an antithrombotic agent. The cyclic flow model has been useful in predicting which agents are likely to be of benefit in clinical trials. PMID- 9973007 TI - Ventricular rate control in chronic atrial fibrillation during daily activity and programmed exercise: a crossover open-label study of five drug regimens. AB - OBJECTIVES: We compared the effects of five pharmacologic regimens on the circadian rhythm and exercise-induced changes of ventricular rate (VR) in patients with chronic atrial fibrillation (CAF). BACKGROUND: Systematic comparison of standardized drug regimens on 24 h VR control in CAF have not been reported. METHODS: In 12 patients (11 male, 69+/-6 yr) with CAF, the effects on VR by 5 standardized daily regimens: 1) 0.25 mg digoxin, 2) 240 mg diltiazem-CD, 3) 50 mg atenolol, 4) 0.25 mg digoxin + 240 mg diltiazem-CD, and 5) 0.25 mg digoxin + 50 mg atenolol; were studied after 2 week treatment assigned in random order. The VR data were analyzed by ANOVA with repeated measures. The circadian phase differences were evaluated by cosinor analysis. RESULTS: The 24-h mean (+/ SD) values of VR (bpm) were - digoxin: 78.9 +/- 16.3, diltiazem: 80.0+/-15.5, atenolol: 75.9+/-11.7, digoxin + diltiazem: 67.3+/-14.1 and digoxin + atenolol: 65.0+/-9.4. Circadian patterns were significant in each treatment group (p < 0.001). The VR on digoxin + atenolol was significantly lower than that on digoxin (p < 0.0001), diltiazem (p < 0.0002) and atenolol (p < 0.001). The time of peak VR on Holter was significantly delayed with regimens 3 and 5 which included atenolol (p < 0.03). During exercise, digoxin and digoxin + atenolol treatments resulted in the highest and lowest mean VR respectively. The exercise Time-VR plots of all groups were nearly parallel (p = ns). The exercise duration was similar in all treatment groups (p = ns). CONCLUSIONS: This study indicates that digoxin and diltiazem, as single agents at the doses tested, are least effective for controlling ventricular rate in atrial fibrillation during daily activity. Digoxin + atenolol produced the most effective rate control reflecting a synergistic effect on the AV node. The data provides a basis for testing the effects of chronic suppression of diurnal fluctuations of VR on left atrial and ventricular function in CAF. PMID- 9973008 TI - Optimal right ventricular pacing site in chronically implanted patients: a prospective randomized crossover comparison of apical and outflow tract pacing. AB - OBJECTIVES: To evaluate the long-term functional and hemodynamic effects of right ventricular outflow tract (RVOT) pacing by comparison with right ventricular apical (RVA) pacing. BACKGROUND: Acute studies have suggested that RVOT pacing could significantly improve cardiac performance in comparison with RVA pacing but no data are available in chronically implanted patients. METHODS: Sixteen patients with chronic atrial tachyarrhythmia and complete AV block were included. Left ventricular ejection fraction (LVEF) was > or =40% in ten and <40% in six. Patients were implanted with a standard DDDR pacemaker connected to two ventricular leads. A screw-in lead was placed at the RVOT and connected to the atrial port. A second lead was positioned at the RVA and connected to the ventricular port. Right ventricular outflow tract and RVA pacing was achieved by programming either the AAIR or the VVIR mode respectively. Four months later patients were randomized so as to undergo either RVOT or RVA pacing for three months according to a blind crossover protocol. Apart from the pacing mode, programming remained unchanged throughout the study. At the end of each period, NYHA class, LVEF, exercise time and maximal oxygen uptake were assessed. RESULTS: No significant difference was observed between the two modes for all the parameters analyzed. These identical results were observed in all patients globally, in patients with LVEF > or =40% as in those with LVEF <40%. CONCLUSIONS: Within the limits of this study, no symptomatic improvement or hemodynamic benefit was noted after three months of RVOT pacing, by comparison with RVA pacing. PMID- 9973009 TI - Influence of right ventricular stimulation site on left ventricular function in atrial synchronous ventricular pacing. AB - OBJECTIVES: The study investigates the correlation between left ventricular function and QRS duration obtained by alternate right ventricular pacing sites. BACKGROUND: 1. Right ventricular apical pacing is associated with alterations of left ventricular contraction sequence. 2. A stimulation producing narrow QRS complexes is supposed to provide for better left ventricular contraction patterns. METHODS: Fourteen patients with third degree AV block received one ventricular pacing lead in apical position. The alternate lead was attached to that site on the septum that produced the smallest QRS complex as measured from the earliest to the last deflection in any of the orthogonal Frank leads (xyz). During atrial synchronous ventricular pacing, the AV delay was optimized individually and for each stimulation site using mitral valve doppler or impedance cardiography. By radionuclide ventriculography, the phase distribution histogram of left ventricular contraction was evaluated as area under the curve (AuC); systolic function was determined as ejection fraction (EF) and as absolute ejected counts (EC) in random order. The difference (delta) in QRS duration between apical and septal stimulation (deltaxyz) was correlated with the difference in phase distribution (deltaAuC) and ejection parameters (deltaEF, deltaEC). RESULTS: QRS duration was shorter with septal than with apical pacing in 9 out of 14 patients (64%); it was longer in 4 (29%), and no difference was seen in 1 patient. There was a significant positive correlation between the change in QRS duration (deltaxvz) and phase distribution (deltaAuC: r = 0.66393, p = 0.010) and a significant negative correlation to systolic function (deltaEF: r = 0.70931, p = 0.004; deltaEC: r = 0.74368, p = 0.002). CONCLUSIONS: In atrial synchronous right ventricular pacing, if the AV delay is adapted individually, decreased QRS duration obtained by alternate pacing sites is significantly correlated with homogenization of left ventricular contraction and with increased systolic function in acute tests. PMID- 9973010 TI - Optimization of ventricular pacing: where should we implant the leads? PMID- 9973011 TI - Auditory stimuli as a trigger for arrhythmic events differentiate HERG-related (LQTS2) patients from KVLQT1-related patients (LQTS1). AB - OBJECTIVE: This study was performed to identify a possible relationship between genotype and phenotype in the congenital familial long QT syndrome (cLQTS). BACKGROUND: The cLQTS, which occurs as an autosomal dominant or recessive trait, is characterized by QT-interval prolongation on the electrocardiogram and torsade de pointes arrhythmias, which may give rise to recurrent syncope or sudden cardiac death. Precipitators for cardiac events are exercise or emotion and occasionally acoustic stimuli. METHODS: The trigger for cardiac events (syncope, documented cardiac arrhythmias, sudden cardiac death) was analyzed in 11 families with a familial LQTS and a determined genotype. RESULTS: The families were subdivided in KVLQT1-related families (LQTS1, n = 5) and HERG (human ether-a-gogo related gene)-related families (LQTS2, n = 6) based on single-strand conformation polymorphism analysis and sequencing. Whereas exercise-related cardiac events dominate the clinical picture of LQTS1 patients, auditory stimuli as a trigger for arrhythmic events were only seen in LQTS2 patients. CONCLUSIONS: Arrhythmic events triggered by auditory stimuli may differentiate LQTS2 from LQTS1 patients. PMID- 9973012 TI - Favorable effects of flecainide in transvenous internal cardioversion of atrial fibrillation. AB - OBJECTIVES: The aim of the study was to evaluate the effects of intravenous (IV) flecainide on defibrillation energy requirements in patients treated with low energy internal atrial cardioversion. BACKGROUND: Internal cardioversion of atrial fibrillation is becoming a more widely accepted therapy for acute episode termination and for implantable atrial defibrillators. METHODS: Twenty-four patients with atrial fibrillation (19 persistent, 5 paroxysmal) underwent elective transvenous cardioversion according to a step-up protocol. After successful conversion in a drug-free state, atrial fibrillation was induced by atrial pacing; IV flecainide (2 mg/kg) was administered and a second threshold was determined. In patients in whom cardioversion in a drug-free state failed notwithstanding a 400- to 550-V shock, a threshold determination was attempted after flecainide. RESULTS: Chronic persistent atrial fibrillation was converted in 13/19 (68%) patients at baseline and in 16/19 (84%) patients after flecainide. Paroxysmal atrial fibrillation was successfully cardioverted in all the patients. A favorable effect of flecainide was observed either in chronic persistent atrial fibrillation (13 patients) or in paroxysmal atrial fibrillation (5 patients) with significant reductions in energy requirements for effective defibrillation (persistent atrial fibrillation: 4.42+/-1.37 to 3.50+/-1.51 J, p < 0.005; paroxysmal atrial fibrillation: 1.68+/-0.29 to 0.84+/-0.26 J, p < 0.01). In 14 patients not requiring sedation, the favorable effects of flecainide on defibrillation threshold resulted in a significant reduction in the scores of shock-induced discomfort (3.71+/-0.83 vs. 4.29+/-0.61, p < 0.005). No ventricular proarrhythmia was observed for any shock. CONCLUSIONS: Intravenous flecainide reduces atrial defibrillation threshold in patients treated with low-energy internal atrial cardioversion. This reduction in threshold results in lower shock induced discomfort. Additionally, flecainide may increase the procedure success rate in patients with chronic persistent atrial fibrillation. PMID- 9973013 TI - Left atrial mechanical function after brief duration atrial fibrillation. AB - OBJECTIVES: This study examined the effect of brief duration atrial fibrillation on left atrial and left atrial appendage mechanical function in humans with structural heart disease. BACKGROUND: Left atrial dysfunction and the development of spontaneous echo contrast (SEC) may follow the cardioversion of atrial fibrillation (AF) to sinus rhythm. This phenomenon has been termed "stunning" and is implicated in the development of atrial thrombus and embolic stroke. The effects of brief duration AF on left atrial mechanical function in humans are unknown. METHODS: Twenty-four patients (23 men, aged 59.1+/-12.7 years) with significant structural heart disease (ejection fraction 31.2+/-9.0%, left atrial diameter 4.9+/-0.4 cm) undergoing implantation of a ventricular cardiodefibrillator underwent transesophageal echocardiography to evaluate left atrial appendage emptying velocities (LAAeV) and SEC before, during and after a 15-min period of AF induced by rapid right atrial pacing. Atrial fibrillation was then permitted to terminate spontaneously within 5 min or was reverted with an endocardial direct current shock. Velocities and SEC were assessed in sinus rhythm pre-AF, during AF and immediately, 5 and 10 min after reversion to sinus rhythm. RESULTS: Atrial fibrillation terminated spontaneously in 10 patients after 16.1+/-1.0 min. Endocardial direct current (DC) cardioversion of 10.4+/-6.4 J was required in 14 patients after AF lasting 20 min. Mean LAAeV pre-AF (50.0 +/ 17.5 cm/s) was not significantly different to LAAeV immediately (52.8 +/- 16.7 cm/s), 5 min (54.3 +/- 16.4 cm/s) or 10 min (53.7 +/- 15.7 cm/s) after reversion to sinus rhythm. Atrial stunning defined as a reduction in LAAeV of >20% was not observed in any patient. Fourteen of 24 patients (58%) developed SEC during AF, which resolved within 30 s of AF termination. There were no significant differences between LAAeV in those patients reverting with DC shock (pre-AF 50.6+/-16.2 cm/s vs. immediately post-AF 54.7+/-16.6 cm/s) or in those patients with spontaneous reversion (pre-AF 48.9+/-20.2 cm/s vs. immediately post-AF 49.8+/-17.3 cm/s). CONCLUSIONS: Significant left atrial stunning was not observed after brief duration AF in humans with structural heart disease. Transient left atrial SEC develops in a significant proportion of these patients during AF but resolves rapidly on reversion to sinus rhythm. These findings suggest that the risk of thromboembolism may be low after brief duration AF that terminates either spontaneously or with an endocardial DC shock even in patients with significant structural heart disease. These findings have important implications for recipients of implantable devices that are capable of atrial defibrillation in response to AF. PMID- 9973015 TI - Human atrial repolarization: effects of sinus rate, pacing and drugs on the surface electrocardiogram. AB - OBJECTIVES: We studied the effects of rate and some cardioactive drugs on the atrial surface electrocardiogram (ECG). BACKGROUND: In atrioventricular block, atrial surface ECG is unmasked. The effect of rate alone permits detection of the effect of other exogenous stimulations such as drugs in the presence of rate alterations. METHODS: High fidelity, high gain ECG leads I, II and III were recorded from 51 patients with heart block. Durations of P and Ta waves and the total PTa interval were measured from nonconducted atrial events. RESULTS: No relationship was found between sinus cycle length and PTa, P or Ta in 31 patients. In 20 patients, progressively decreasing the atrial pacing cycle length from 853 ms to 381 ms resulted in a linear reduction of the PTa interval from 444 to 291 ms (rho = 0.76, slope = 0.24). This was largely due to shortening of Ta. A linear rate correction formula was derived: corrected PTa = PTa - 0.24 (PP - 1000). Atropine (0.02 mg/kg) shortened the PP interval (p < 0.001) and the PTa interval (p < 0.01). Propranolol (0.1 mg/kg) prolonged the PP interval (p < 0.001) but did not alter the PTa interval. Neither disopyramide (2.0 mg/kg) nor flecainide acetate (2.0 mg/kg) altered the PP interval, but both prolonged the PTa interval (p < 0.001). This was largely due to P wave lengthening after flecainide (p < 0.001) and to Ta prolongation after disopyramide (p < 0.001). CONCLUSIONS: In heart block, PTa, P and Ta waves can be measured reliably. The effects of pacing and some antiarrhythmic drugs on the atrial myocardium are similar to those known at the ventricular level. PMID- 9973014 TI - Triggering mechanism for neurally mediated syncope induced by head-up tilt test: role of catecholamines and response to propranolol. AB - OBJECTIVES: We studied the triggering mechanism for neurally mediated syncope. BACKGROUND: Although increased transient sympathetic tone is thought to be necessary for the development of neurally mediated syncope, little is known about the triggering mechanism for neurally mediated syncope. METHODS: Plasma epinephrine (EP) and norepinephrine (NE) levels were assessed in 20 syncope patients during tilt test (80 degrees, 15 min) with and without isoproterenol (ISP, 0.01, 0.02 microg/kg/min). If syncope occurred, propranolol (0.1 mg/kg) was injected. RESULTS: Eight patients experienced syncope during tilting alone, and 9 patients required ISP for syncope. In the negative response without ISP, NE showed a small statistical 1.7-fold increase at end of tilting and EP did not change during tilting. When syncope occurred during tilting alone, a significant 11.7-fold increase in EP at syncope was registered concomitant with a small 2.5 fold increase in NE. When patients experienced syncope during tilting with ISP, a significant 5.0-fold increase in EP at syncope was registered concomitant with a small 1.7-fold increase in NE. In patients without ISP, propranolol did not interrupt syncope. In patients with ISP, six of eight receiving propranolol responded to tilting negatively. CONCLUSIONS: An increase of NE levels may result in inhibition of syncope and an EP surge may be a triggering mechanism for neurally mediated syncope. Comparatively low levels of EP may be enough to induce syncope during tilting with ISP compared with tilting alone. Propranolol is not effective in patients without ISP, but it frequently inhibits syncope in patients with ISP. Propranolol (0.1 mg/kg) may be insufficient to block the actions of high levels of circulating EP. PMID- 9973016 TI - Clinical course of persistent junctional reciprocating tachycardia. AB - OBJECTIVE: The purpose of this study is to review the clinical course of persistent junctional reciprocating tachycardia (PJRT) in 21 patients spanning a wide age range to examine the electrophysiologic characteristics of the conduction system in these patients with PJRT, particularly in regards to its incessant nature and to evaluate the long-term response to radiofrequency ablation. BACKGROUND: Persistent junctional reciprocating tachycardia is uncommon, occurring in 1% of patients with supraventricular tachycardia. Its presentation, course and treatment are incompletely characterized. METHODS: The clinical, electrocardiographic, electrophysiologic and echocardiographic data of 21 patients with PJRT were reviewed. RESULTS: In 9 of these 21 patients, the mean tachycardia cycle length increased significantly (p < 0.0001) as the patients grew, from a mean tachycardia cycle length of 308+/-64 ms in the patients less than 2 years, 414+/-57 ms in the patients between 2 years and 5 years, to 445+/ 57 ms in the patients greater than 5 years, primarily due to slowing of retrograde conduction in the accessory pathway. Persistent junctional reciprocating tachycardia was associated with impaired ventricular function in 11, improving spontaneously in 4 and, after successful ablation of the accessory pathway, in 7. All patients except one were uncontrolled on one or more medications. Ablation of the accessory pathway was successful in 19 of 21 patients. CONCLUSIONS: We conclude that PJRT is characterized by an onset in early childhood and by an age-related prolongation of the tachycardia cycle length mediated primarily through conduction delay in the concealed, retrogradely conducting accessory pathway. Ablation of the accessory pathway provides definitive treatment for PJRT. PMID- 9973017 TI - Variation of P-QRS relation during atrioventricular node reentry tachycardia. AB - OBJECTIVES: The main objective of this study was to characterize the phenomenon of variation in the P-QRS relation during atrioventricular node reentry tachycardia. BACKGROUND: Variation of P-QRS relation during tachycardia has been observed occasionally in atrioventricular node reentry tachycardia. However, the incidence, the characteristics and the mechanisms of this phenomenon have not been investigated previously. METHODS: Retrospective analysis was performed in 311 consecutive patients with slow-fast form and 108 patients with atypical or multiple form of atrioventricular node reentry tachycardia to examine whether variation of P-QRS relation with changes in AH, HA and AH/HA (A = atria; H = His bundle) ratio occurred during tachycardia. RESULTS: A total of 28 patients, 8 with slow-fast and 20 with atypical or multiple tachycardias, were found to manifest this phenomenon. There were 6 males and 22 females, with an average age of 38+/-16 years. In 10 patients, this phenomenon occurred transiently following electrical induction of the tachycardia. In 15 patients, changes in AH, HA and AH/HA ratio were associated with the occurrence of Wenckebach or 2:1 block proximal to the His bundle (H) recording site without interruption of the tachycardia. In nine patients, three with nonsustained tachycardia and six after administration of adenosine triphosphate, this phenomenon was observed at the termination of the tachycardia. This phenomenon was usually accompanied by a mild lengthening of the tachycardia cycle length. CONCLUSIONS: Variation of P-QRS relation with or without block may occur during atrioventricular node reentry tachycardia, especially in atypical or multiple-form tachycardias. It was postulated that decremental conduction in the distal common pathway, which exists between the distal link of the reentry circuit and the H, is primarily responsible for this phenomenon. PMID- 9973018 TI - Improved diagnostic value of combined time and frequency domain analysis of the signal-averaged electrocardiogram after myocardial infarction. AB - BACKGROUND: Time domain analysis (TD) of the signal-averaged electrocardiogram (SAECG) presents a higher incidence of false positives in inferior myocardial infarction (MI), whereas spectral turbulence analysis (STA) suffers from a higher incidence of false positives in anterior MI. We investigated the hypothesis that a combined TD and STA (TD+STA) analysis of the SAECG could improve its predictive accuracy for major arrhythmic events (MAE) after MI. METHODS: Signal-averaged electrocardiograms were prospectively recorded 10.1 +/- 2.6 days after acute MI in 602 patients. Time domain analysis and STA were performed using standard parameters and criteria for abnormality. For the combined TD+STA model, stepwise discriminant analysis was utilized to optimize prediction of MAE. Receiver operating characteristic curves were utilized to optimize cutoff values for each SAECG parameter separately, and also for the combined TD+STA model. RESULTS: During a one-year follow-up period, 38 patients had MAE: 14 sustained ventricular tachycardia, 2 resuscitated ventricular fibrillation and 22 sudden cardiac deaths. The total predictive accuracy of combined TD+STA (89.9%) was significantly higher than TD (75.1%) or STA (77.6%). The negative predictive accuracy of all three analyses was high (98%). The positive predictive accuracy of TD (19.6%) or STA (18.3%) was quite low, and significantly improved to 35.8% by combined TD+STA analysis. The positive predictive accuracy of TD+STA improved to 51.2% in patients with left ventricular ejection fraction <40%. CONCLUSIONS: Combined TD + STA analysis of the SAECG significantly improves its prognostic ability for MAE in post-MI patients compared with TD or STA analyzed separately. PMID- 9973019 TI - A randomized trial comparing the impact of a nonionic (Iomeprol) versus an ionic (Ioxaglate) low osmolar contrast medium on abrupt vessel closure and ischemic complications after coronary angioplasty. AB - OBJECTIVES: To assess the effect of nonionic versus ionic contrast media on abrupt vessel closure and major ischemic complications after coronary angioplasty. BACKGROUND: There is a continuous debate about the "thrombogenic potential" of nonionic contrast media. The results of both in vitro and in vivo investigations are incongruent. METHODS: We prospectively evaluated the outcomes of 2,000 patients undergoing percutaneous transluminal coronary angioplasty (PTCA). According to a randomized, double-blind protocol, they received either iomeprol (nonionic; n = 1,001) or ioxaglate (ionic; n = 999). Intracoronary thrombus before PTCA was found more often in the iomeprol group (4.2% vs 2.7%, p = 0.04). No other significant differences between both groups were observed with regard to pre-PTCA clinical and angiographic characteristics. RESULTS: The frequency of reocclusions necessitating repeat angioplasty occurring either in laboratory (2.9% with iomeprol and 3.0% with ioxaglate) or out of laboratory (3.1% vs 4.1%) was not significantly different. The rate of major ischemic complications was also comparable after both contrast media (emergency bypass surgery: 0.8% vs 0.7%, myocardial infarction: 1.8 vs 2.0%, cardiac death during hospital stay: 0.2% vs 0.2%). In the iomeprol group, more patients had dissections post-PTCA (30.2% vs 25.0%, p = 0.01) and more patients received intracoronary stents (31.6% vs 25.7%, p = 0.004). Allergic reactions requiring treatment occurred only in the ioxaglate group (0.0% vs 0.9%, p = 0.002). CONCLUSIONS: The nonionic contrast medium was not associated with a higher rate of abrupt vessel closure requiring repeat angioplasty, or major ischemic events. These data suggest that nonionic contrast media do not increase the risk of thrombotic complications in patients undergoing coronary interventions. PMID- 9973020 TI - A prospective randomized trial of prevention measures in patients at high risk for contrast nephropathy: results of the P.R.I.N.C.E. Study. Prevention of Radiocontrast Induced Nephropathy Clinical Evaluation. AB - OBJECTIVES: This study was done to test the hypothesis that a forced diuresis with maintenance of intravascular volume after contrast exposure would reduce the rate of contrast-induced renal injury. BACKGROUND: We have previously shown a graded relationship with the degree of postprocedure renal failure and the probability of in-hospital death in patients undergoing percutaneous coronary intervention. Earlier studies of singular prevention strategies (atrial natriuretic factor, loop diuretics, dopamine, mannitol) have shown no clear benefit across a spectrum of patients at risk. METHODS: A prospective, randomized, controlled, single-blind trial was conducted where 98 participants were randomized to forced diuresis with intravenous crystalloid, furosemide, mannitol (if pulmonary capillary wedge pressure <20 mm Hg), and low-dose dopamine (n = 43) versus intravenous crystalloid and matching placebos (n = 55). RESULTS: The groups were similar with respect to baseline serum creatinine (2.44+/-0.80 and 2.55+/-0.91 mg/dl), age, weight, diabetic status, left ventricular function, degree of prehydration, contrast volume and ionicity, and extent of peripheral vascular disease. The forced diuresis resulted in higher urine flow rate (163.26+/-54.47 vs. 122.57+/-54.27 ml/h) over the 24 h after contrast exposure (p = 0.001). Two participants in the experimental arm versus five in the control arm required dialysis, with all seven cases having measured flow rates <145 ml/h in the 24 h after the procedure. The mean individual change in serum creatinine at 48 h, the primary end point, was 0.48+/-0.86 versus 0.51+/-0.87, in the experimental and control arms, respectively, p = 0.87. There were no differences in the rates of renal failure across six definitions of renal failure by intent to-treat analysis. However, in all participants combined, the rise in serum creatinine was related to the degree of induced diuresis after controlling for baseline renal function, r = -0.36, p = 0.005. The rates of renal failure in those with urine flow rates greater than 150 ml/h in the postprocedure period were significantly lower, 8/37 (21.6%) versus 28/61 (45.9%), p = 0.03. CONCLUSIONS: Forced diuresis with intravenous crystalloid, furosemide, and mannitol if hemodynamics permit, beginning at the start of angiography provides a modest benefit against contrast-induced nephropathy provided a high urine flow rate can be achieved. PMID- 9973021 TI - Effect of age on outcome with primary angioplasty versus thrombolysis. AB - OBJECTIVES: The purpose of this study was to determine how risks associated with increasing age differed in patients treated with percutaneous transluminal coronary angioplasty versus thrombolysis. BACKGROUND: Advancing age is a risk factor for adverse outcome in patients with acute myocardial infarction. Primary angioplasty has been thought to be particularly beneficial in higher risk patients including the elderly. There is, however, limited data on any differential incremental benefit of angioplasty compared with thrombolysis in candidates for either treatment. METHODS: In the GUSTO-IIb angioplasty substudy, 1,138 patients were randomized to receive primary angioplasty or accelerated tissue-type plasminogen activator (t-PA). The effect of age on outcome was assessed as a discrete and continuous variable for each treatment group. Models using age as a linear factor as well as cubic spline transformations were used for the major end points of 30-day death or disabling stroke; death or reinfarction; and death, reinfarction or disabling stroke. RESULTS: For each 10 year patient group, outcome was improved with angioplasty (n = 565) compared with t-PA (n = 573). Irrespective of treatment, however, risk increased with age. After adjusting for baseline characteristics, each increment of 10 years of age increased the risk of death or myocardial infarction by 1.32 (95% confidence interval 1.04 to 1.76, p = 0.022). For all adverse outcomes, this incremental effect of increasing age was constant. CONCLUSIONS: Advancing age is associated with worse outcomes, and the risks increase in proportion to age. Although primary angioplasty improves outcomes over thrombolysis, it does not appear to be more beneficial in older than in younger patient groups. The incremental adverse effect of age does not vary by treatment strategy. PMID- 9973022 TI - Procedural results and late clinical outcomes following multivessel coronary stenting. AB - OBJECTIVES: To evaluate in-hospital and long-term clinical outcomes in a large consecutive series of patients undergoing percutaneous multivessel stent intervention. BACKGROUND: High restenosis and recurrent angina rates have limited the clinical outcomes of multivessel coronary angioplasty before stents were available to improve angioplasty results. METHODS: We evaluated in-hospital and long-term clinical outcomes (death, Q-wave myocardial infarction [MI], and repeat revascularization rates at one year) in 398 consecutive patients treated with coronary stents in two (94% of patients) or three native arteries, compared to 1,941 patients undergoing stenting procedure in a single coronary artery between January 1, 1994 and August 29, 1997. RESULTS: Overall procedural success was obtained in 96% of patients with two- or three-vessel stenting and in 970% of patients with single-vessel stent intervention (p = 0.36). Procedural complications were also similar (3.8% for multivessel versus 2.9% for single vessel, p = 0.14). During follow up, target lesion revascularization was 15% in multivessel and 16% in single-vessel interventions (p = 0.38), and repeat revascularization (calculated per treated patient) was also similar for both groups (20% vs. 21%, p = 0.73). There was no difference in death (1.4% vs. 0.7%, p = 0.26), and Q-wave MI (1.2% vs. 0%, p = 0.02) was lower following multivessel interventions. Overall cardiac event-free survival was similar for both groups (p = 0.52). CONCLUSIONS: Unlike previous conventional angioplasty experiences, multivessel stenting has (1) similar in-hospital procedural success and major complication rates and (2) similar long-term (one year) clinical outcomes compared with single-vessel stenting. Thus, stents may be a viable therapeutic strategy in carefully selected patients with multivessel coronary disease. PMID- 9973023 TI - Real-time measurement of radiation exposure to patients during diagnostic coronary angiography and percutaneous interventional procedures. AB - OBJECTIVES: The aim of this study was to accurately assess the radiation exposure received by patients during cardiac catheterization in a large sample representative of the current state of practice in cardiac angiography. BACKGROUND: Radiation exposure to patients and laboratory staff has been recognized as a necessary hazard in coronary angiography. The effects on x-ray exposure of the increased complexity of coronary angiographic procedures and, in particular, the increasing use of coronary artery stenting, have not been adequately addressed in previous studies. METHODS: X-ray exposure measurements were performed on a consecutive series of 972 patients undergoing 992 diagnostic and interventional studies in the Mayo Clinic catheterization laboratory within an eight week period in late 1997. Data were acquired from 706 diagnostic procedures and 286 interventional procedures using a real-time exposure measurement system to continuously calculate and record the exposure rate and total exposure, reflecting all parameters relevant to the specific patient and procedure situation. RESULTS: The median exposure for all 992 procedures was 41.8 mC/kg (162.1 R); the corresponding values for diagnostic and interventional procedures were 34.9 and 95.6 mC/kg, respectively (135.3 vs. 370.5 R). There were significant differences in the fluoroscopy exposure time between diagnostic and interventional procedures: 4.7 min vs. 21.0 min. Heavier patients (>83 kg) received x-ray exposures at a significantly higher rate than did lighter patients (<83 kg) during both fluoroscopy and cine; 44.9 mC/kg/min (173.9 R/min) vs. 27.9 mC/kg/min (108.3 R/min) for cine exposure rate and 2.3 mC/kg/min (8.8 R/min) vs. 1.5 mC/kg/min (5.8 R/min) for fluoroscopy exposure rate. CONCLUSIONS: Changes in practice have led to higher values for patient x-ray radiation exposures during cardiac catheterization procedures. The real-time display and recording of x-ray exposure facilitates the reduction of exposure in the catheterization laboratory. PMID- 9973024 TI - Quantity and function of high density lipoprotein as an indicator of coronary atherosclerosis. AB - OBJECTIVES: To examine the association between the fractional esterification rate of cholesterol (C) in low density lipoprotein- and very low density lipoprotein depleted plasma (FER(HDL)) and coronary artery disease (CAD) and the influence of serum HDL-C levels. BACKGROUND: The function of HDL in reverse cholesterol transport is involved in the antiatherogenic action of HDL, and FER(HDL) is a newly established quantitative measure of HDL function in vivo. METHODS: Cases (n = 185, F/M: 43/142) and controls (n = 74, F/M:27/47) were defined as subjects with/without angiographically proven CAD, respectively. RESULTS: The cases had significantly (p < 0.05) higher FER(HDL) values (13.2+/-0.3 %/h vs. 12.1+/-0.5 %/h) and lower HDL-C levels (39.0+/-1.0 mg/dL vs. 46.8+/-1.4 mg/dL) than the controls. The associations of FER(HDL) and HDL-C with CAD were linear and significant (p < 0.05). Multiple logistic regression analysis indicated that the association of FER(HDL) with CAD varied with the HDL-C level: significant for the low HDL-C tertile (chi-square = 6.20, p < 0.05) but not significant for the middle and high HDL-C tertiles (chi-square = 0.08 and 0.03, n.s.). The risk of CAD, relative to that in patients with low FER(HDL) and high HDL-C, was higher in patients with low FER(HDL) and low HDL-C (odds ratio [95% confidence interval]: 2.37 [1.12-4.97], p < 0.05) and was highest in patients with high FER(HDL) and low HDL-C (3.85 [1.84-8.06], p < 0.01). CONCLUSIONS: The functional assay of HDL (FER(HDL)) is an independent risk factor for CAD. The combination of FER(HDL) and HDL-C could be a potent indicator for CAD, and may reflect a potential mechanism of atherosclerosis. PMID- 9973025 TI - An algorithm for noninvasive identification of angiographic three-vessel and/or left main coronary artery disease in symptomatic patients on the basis of cardiac risk and electron-beam computed tomographic calcium scores. AB - OBJECTIVES: We sought to model an algorithm for noninvasive identification of angiographically obstructive three-vessel and/or left main disease based on conventional cardiac risk assessment and site and extent of coronary calcium determined by electron-beam computed tomography (EBCT). BACKGROUND: Such an algorithm would greatly facilitate clinical triage in symptomatic patients with no previous diagnosis of coronary artery disease (CAD). METHODS: We examined 291 patients with suspected, but not previously diagnosed, CAD who underwent coronary angiography for clinical indications. Cardiac risk factors were determined as defined by the National Cholesterol Education Program. An EBCT scan was performed in all patients, and a coronary calcium score (Agatston method) was computed. Total per-patient calcium scores and separate scores for the major coronary arteries were generated. These scores were also analyzed for localization of coronary calcium in the more distal versus proximal tomographic sections. These parameters and the risk factors were considered for the model described in the following section. RESULTS: Sixty-eight patients (23%) had angiographic three vessel and/or left main CAD. Multiple logistic regression analysis determined male sex, presence of diabetes and left anterior descending (LAD) and circumflex (LCx) coronary calcium scores, independent from more distal calcium localization, as independent predictors for identification of three-vessel and/or left main CAD. Based on this four variable model, a simple noninvasive index (NI) was constructed as the following: loge(LAD score) + log(e)(LCx score) + 2[if diabetic] + 3[if male]. Receiver operating characteristic curve analysis for this NI yielded an area under the curve of 0.88+/-0.03 (p < 0.0001) for separating patients with, versus without, angiographic three-vessel and/or left main CAD. Various NI cutpoints demonstrated sensitivities from 87-97% and specificities from 46-74%. The NI values >14 increased the probability of angiographic three vessel and/or left main CAD from 23% (pretest) to 65-100% (posttest), and NI values <10 increased the probability of no three-vessel and/or left main CAD from 77% (pretest) to 95-100% (posttest). CONCLUSIONS: On the basis of a simple algorithm ("noninvasive index"), EBCT calcium scanning in conjunction with risk factor analysis can rule in or rule out angiographically severe disease, i.e., three-vessel and/or left main CAD, in symptomatic patients. PMID- 9973026 TI - Coronary calcification by electron beam computed tomography and obstructive coronary artery disease: a model for costs and effectiveness of diagnosis as compared with conventional cardiac testing methods. AB - OBJECTIVES: The purpose of this study was to determine if electron beam computed tomography (EBCT) has potential as a cost-effective approach to diagnosis of obstructive coronary disease. BACKGROUND: Coronary calcification quantified by EBCT is closely related to the extent of atherosclerosis. METHODS: A model based upon published sensitivities (Se)/specificities (Sp) for diagnosis in an ambulatory patient of obstructive coronary disease (> or =50% stenosis) and population prevalence was tested for angiography alone, or treadmill exercise, stress echocardiography, stress thallium or predetermined EBCT calcium score outpoints, followed by angiography if indicated. RESULTS: Total direct testing costs increased in proportion to disease prevalence whereas cost-effectiveness, direct costs/patient diagnosed correctly with disease, decreased as a function of prevalence. Using an EBCT calcium score of 168 (Se/Sp = 71%/90%) provided for the least costly and most cost-effective noninvasive pathway. Calcium scores of 80 (Se/Sp = 84%/84%) and 37 (Se/Sp = 90%/77%) were also cost-effective when prevalence of disease was < or =70%; but results for a >0 calcium score (Se/Sp = 95%/46%) cutpoint were not superior to conventional methods. Calcium score cutpoints of 37, 80 or 168 provided similar or superior overall negative and positive predictive values to conventional noninvasive testing pathways across all prevalence subgroups. CONCLUSIONS: In ambulatory patients evaluated for obstructive coronary disease, a testing pathway utilizing quantification of coronary calcium by EBCT as an initial noninvasive testing approach minimized direct costs, and maximized cost-effectiveness in population groups with low/ moderate disease prevalence (< or =70%); as expected, direct angiography as the first and only test proved most cost-effective in patients with a high prevalence (>70%) of disease. PMID- 9973027 TI - Gender differences in myocardial blood flow dynamics: lipid profile and hemodynamic effects. AB - OBJECTIVES: The purpose of the study was to compare myocardial blood flow (MBF) in hyperlipidemic postmenopausal women and age-matched hyperlipidemic men, and to analyze the relationship between cholesterol subfractions and myocardial blood flow in men and women. BACKGROUND: Women are protected from coronary artery disease (CAD) events until well after menopause, in part due to gender-specific differences in lipid profiles. METHODS: To examine the effect of these influences on coronary microcirculation, MBF was quantitated with N-13 ammonia/PET (positron emission tomography) at rest and during adenosine hyperemia in 15 women and 15 men, all nondiabetic, who were matched for age and total cholesterol levels (53+/ 4 vs. 50+/-8 years, p = NS, 6.44+/-1.1 vs. 6.31+/-0.85 mmol/liter, or 249+/-41 vs. 244+/-33 mg/dl, p = NS). RESULTS: Women had significantly higher high density lipoprotein (HDL) and lower triglyceride (Tg) levels than did men, and they showed significantly higher resting MBF and stress MBF levels. Significant correlations were found between resting and hyperemic MBF and HDL and Tg levels (r = 0.44, p < 0.02 for stress MBF vs. HDL; r = 0.48, p < 0.007 for stress MBF vs. Tg). Gender was the strongest predictor of hyperemic MBF in multivariate analysis. Women responded to adenosine hyperemia with a significantly higher heart rate than did men, and hemodynamic factors correlated significantly with blood flow both at rest and during stress. CONCLUSIONS: These data suggest that the favorable lipid profile seen in women may be associated with preserved maximal blood flow in the myocardium. PMID- 9973028 TI - Ability of troponins to predict adverse outcomes in patients with renal insufficiency and suspected acute coronary syndromes: a case-matched study. AB - OBJECTIVES: The purpose of this study was to investigate the utility of cardiac troponin T and troponin I for predicting outcomes in patients presenting with suspected acute coronary syndromes and renal insufficiency relative to that observed in similar patients without renal disease. BACKGROUND: Cardiac troponin T and troponin I have shown promise as tools for risk stratification of patients with acute coronary syndromes. However, there is uncertainty regarding their cardiac specificity and utility in patients with renal disease. METHODS: We measured troponin T, troponin I and creatine kinase MB in 51 patients presenting with suspected acute coronary syndromes and renal insufficiency and in 102 patients without evidence of renal disease matched for the same peak troponin T or I value, selected from a larger patient cohort. Blood samples were obtained at presentation to an emergency room 4 hours, 8 hours and 16 hours later. The ability of biochemical markers to predict adverse outcomes in both groups including infarction, recurrent ischemia, bypass surgery, heart failure, stroke, death or positive angiography/angioplasty during hospitalization and at six months was assessed by receiver-operator curve analysis. The performance of both troponins was compared between groups. RESULTS: Thirty-five percent of patients in the renal group and 45% of patients in the nonrenal group experienced an adverse initial outcome; over 50% of patients in all groups had experienced an adverse outcome by 6 months, but these differences were not significant. The area under the curve (AUC) for the ROC curve for troponin T as predictor of initial outcomes was significantly lower in the renal group than in the nonrenal group: 0.56+/-0.07 and 0.75+/-0.07, respectively. The area under the curve was also significantly lower in the renal group compared with the nonrenal group for troponin T as predictor of six month outcomes: 0.59+/-0.07 and 0.74+/-0.07, respectively. The area under the curve was also significantly lower in the renal group compared to the nonrenal group for troponin I as predictor of both initial and six month outcomes: 0.54+/-0.06 vs. 0.71+/-0.07 and 0.53+/- 0.06 vs. 0.65+/ 0.07, respectively. The sensitivity of troponin T for both initial and six month adverse outcomes was significantly lower in the renal group than in the nonrenal group at a similar level of specificity (0.87): 0.29 vs. 0.60 and 0.45 vs. 0.56, respectively. Troponin I also exhibited similar differences in sensitivity in the renal group (0.29 vs. 0.50 and 0.33 vs. 0.40, respectively). CONCLUSIONS: The ability of cardiac troponin T and troponin I to predict risk for subsequent adverse outcomes in patients presenting with suspected acute coronary syndromes is reduced in the presence of renal insufficiency. PMID- 9973029 TI - Fatal cardiac rupture among patients treated with thrombolytic agents and adjunctive thrombin antagonists: observations from the Thrombolysis and Thrombin Inhibition in Myocardial Infarction 9 Study. AB - OBJECTIVES: The purpose of this study was to determine the incidence and demographic characteristics of patients experiencing cardiac rupture after thrombolytic and adjunctive anticoagulant therapy and to identify possible associations between the mechanism of thrombin inhibition (indirect, direct) and the intensity of systemic anticoagulation with its occurrence. BACKGROUND Cardiac rupture is responsible for nearly 15% of all in-hospital deaths among patients with myocardial infarction (MI) given thrombolytic agents. Little is known about specific patient- and treatment-related risk factors. METHODS Patients (n = 3,759) with MI participating in the Thrombolysis and Thrombin Inhibition in Myocardial Infarction 9A and B trials received intravenous thrombolytic therapy, aspirin and either heparin (5,000 U bolus, 1,000 to 1,300 U/h infusion) or hirudin (0.1 to 0.6 mg/kg bolus, 0.1 to 0.2 mg/kg/h infusion) for at least 96 h. A diagnosis of cardiac rupture was made clinically in patients with sudden electromechanical dissociation in the absence of preceding congestive heart failure, slowly progressive hemodynamic compromise or malignant ventricular arrhythmias. RESULTS A total of 65 rupture events (1.7%) were reported-all were fatal, and a majority occurred within 48 h of treatment Patients with cardiac rupture were older, of lower body weight and stature and more likely to be female than those without rupture (all p < 0.001). By multivariable analysis, age >70 years (odds ratio [OR] 3.77; 95% confidence interval [CI] 2.06, 6.91), female gender (OR 2.87; 95% CI 1.44, 5.73) and prior angina (OR 1.82; 95% CI 1.05, 3.16) were independently associated with cardiac rupture. Independent predictors of nonrupture death included age >70 years (OR 3.68; 95% CI 2.53, 5.35) and prior MI (OR 2.14; 95%, CI 1.45, 3.17). There was no association between the type of thrombin inhibition, the intensity of anticoagulation and cardiac rapture. CONCLUSIONS Cardiac rupture following thrombolytic therapy tends to occur in older patients and may explain the disproportionately high mortality rate among women in prior dinical trials. Unlike major hemorrhagic complications, there is no evidence that the intensity of anticoagulation associated with heparin or hirudin administration influences the occurrence of rupture. PMID- 9973030 TI - CASS Registry long term surgical survival. Coronary Artery Surgery Study. AB - OBJECTIVES: To show the effect of clinical, angio and demographic traits on late survival of Coronary Artery Surgery Study (CASS) patients following coronary artery bypass grafting (CABG) and introduce Hazard Function analysis to CASS survival data. METHODS: Patients were reached by mail survey with 94% response. By National Death Index, vital status was obtained in 99.7% (n = 8221) with a mean follow up of 15 years. Cox proportional hazard and Blackstone Hazard Function regressions were used to assess effects of preoperative traits. RESULTS: Ninety percent of patients were alive at 5, 74% at 10 and 56% at 15 years. Of those age 65 and age 75 at operation, 74% and 59% were living at 10 years and 54% and 33% at 15 years (now age 90), survival exceeding the matched U.S. population. Hazard Function falls rapidly after CABG to 9 to 12 months, then rises, doubling by 15 years. Young patients, below age 35, had lower late survival. The time segmented Cox model (divided at time suggested by the Hazard Function) identified traits showing predictive power early, throughout and late. Female sex, small body surface, ischemic symptoms and emergency status affected survival early. Heavier weight, infarct(s), diuretics, diabetes, smoking, left main and LAD stenosis and use of vein grafts only increased hazard late only. CONCLUSIONS: There are still lessons from the CASS database. CABG in the elderly is supported by the survival pattern of our patients age 75 at operation. Time-segmented Cox analysis and Hazard Function analysis separate baseline variables into those that predict early mortality and those that predict long survival. PMID- 9973031 TI - Effect of vitamin E on endothelial vasodilator function in patients with hypercholesterolemia, chronic smoking or both. AB - OBJECTIVES: The purpose of this study was to test the hypothesis that long-term supplementation with Vitamin E improves endothelium-dependent relaxation in hypercholesterolemia patients and/or chronic smoking, two risk factors that have been shown to be associated with increased radical formation. BACKGROUND: Experimental evidence suggests that oxidized low density lipoprotein (LDL) impairs endothelium-dependent relaxation, and vitamin E, a lipid-soluble antioxidant, reduces the oxidation of LDL. METHODS: Thirteen subjects with hypercholesterolemia, 14 smokers and 15 hypercholesterolemic smokers were enrolled in a double-blind, placebo-controlled study. After baseline measurements of plasma autoantibodies against oxidized LDL and assessment of endothelium dependent relaxation using intra-arterial forearm infusions of acetylcholine, participants within each group were randomly assigned in a 1:2 fashion to receive either placebo or vitamin E for 4 months, when plasma levels of autoantibodies against oxidized LDL and vascular function were reassessed. RESULTS: Vitamin E significantly augmented endothelium-dependent relaxation in hypercholesterolemic smokers but not in patients with either hypercholesterolemia or chronic smoking. At baseline, hypercholesterolemic smokers had significantly higher autoantibody levels against oxidized LDL (compared with the other two groups), which were significantly reduced after 4 months of vitamin E supplementation. There was a significant relationship between improvement in acetylcholine-induced vasodilation and the change in autoantibody titer against oxidized LDL (r = 0.59; p = 0.002). CONCLUSIONS: Long-term vitamin E supplementation improves endothelium-dependent relaxation in forearm resistance vessels of hypercholesterolemic smokers, which are characterized by increased levels of autoantibodies against oxidized LDL. These findings may suggest that the beneficial effect of vitamin E is confined to subjects with increased exposure to oxidized LDL. PMID- 9973032 TI - Nonexercise stress transthoracic echocardiography: transesophageal atrial pacing versus dobutamine stress. AB - OBJECTIVES: To compare transesophageal atrial pacing stress echocardiography with dobutamine stress echocardiography for feasibility, safety, duration, patient acceptance and concordance in inducing wall motion abnormalities. BACKGROUND: Transesophageal atrial pacing is an effective method of increasing heart rate and has been used in the assessment of coronary artery disease. METHODS: Both tests were performed in sequence on the same patients in random order. Transesophageal atrial pacing stress echocardiography began at a heart rate of 10 beats/min above the baseline value and was increased by 20 beats/min every two min until 85% of the age-predicted maximum heart rate or another end point was reached. Dobutamine echocardiography was performed using three-min stages and a maximum dose of 40 microg/kg per min. Atropine (total dose < or =2 mg) was administered at the start of the 40 microg/kg per min stage if needed to augment heart rate or during pacing if Wenckebach heart block occurred. RESULTS: Transesophageal atrial pacing stress echocardiography was feasible in 100 of 104 patients (96%); the duration (8.6+/-3.6 min) was significantly shorter than that of dobutamine stress echocardiography (15.1+/-3.9 min) (p = 0.0001). With transesophageal atrial pacing stress echocardiography, the recovery period was shorter, symptoms and dysrhythmias were fewer, hypertension and hypotension were less common and target heart rate was more frequently achieved. No complications occurred with either test. Patient acceptance was satisfactory. Agreement between results of both tests was good for segmental wall motion scoring with a 16-segment model, scores 1 to 5 (kappa: rest, 0.79; peak, 0.57) and test interpretation (normal, ischemia, infarction or resting wall motion abnormality with ischemia) (kappa: 0.77). CONCLUSIONS: Transesophageal atrial pacing stress echocardiography is a feasible, well-tolerated alternative to dobutamine stress echocardiography. It can be performed rapidly and shows good agreement with dobutamine stress echocardiography in the induction of myocardial ischemia. PMID- 9973033 TI - Dobutamine-atropine stress echocardiography for risk stratification in patients with chronic left ventricular dysfunction. AB - OBJECTIVE: To assess the prognostic value of sustained improvement, scar and inducible ischemia with or without viability in patients with chronic left ventricular dysfunction (LVD). BACKGROUND: Dobutamine-atropine stress echocardiography (DASE) accurately detects scar, reversible dysfunction and the extent of coronary artery disease in LVD. METHODS: Three hundred fifty consecutive patients (age 62+/-13 years, mean+/-SD, 215 men/135 women) with moderate to severe LVD (LVEF < 40%, mean 30+/-8%) underwent DASE and were followed for > or =18 months. Dobutamine-atropine stress echocardiographic findings were classified according to sustained improvement in all vascular territories, scar, inducible ischemia (worsening wall motion at peak dose only or biphasic responses) and their extent. RESULTS: Sustained improvement occurred in 83 patients (24%), scar alone in 99 (28%) and inducible ischemia in 168 (48%, with biphasic responses in 104). Ischemia was induced in all vascular territories in 26 patients. Patients with sustained improvement or scar alone were treated medically, whereas 46% (78/168) with inducible ischemia were revascularized (coronary bypass surgery, n = 67 or angioplasty, n = 11). There were 76 hard events including cardiac death in 59, nonfatal myocardial infarction in 11, and resuscitated sudden death in 6. Hard events were rare in sustained improvement (5%, 4/83), uncommon in scar (13%, 13/99) and common (p < 0.01) in medically treated patients with inducible ischemia (59%, 53/90). Cardiac deaths were especially common (p < 0.01) in patients with biphasic responses (55%, 28/51). Inducible ischemia independently predicted hard events (chi2 = 75.35, p < 0.001) along with reduced LVEF at peak dose (chi2 = 8.38, p = 0.004). Hard cardiac events were uncommon (8%, 6/78, p < 0.001) in patients with inducible ischemia who underwent early revascularization. CONCLUSIONS: Inducible ischemia during DASE was the major determinant of outcome in LVD and independent of clinical data and left ventricular function. Improved wall thickening alone and scar alone predicted good outcome. Survival of patients with inducible ischemia was better after revascularization. PMID- 9973034 TI - Limited myocardial contractile reserve and chronotropic incompetence in patients with chronic Chagas' disease: assessment by dobutamine stress echocardiography. AB - OBJECTIVES: To determine whether dobutamine stimulation in patients with Chagas' disease may uncover abnormal contractile responses as seen in ischemic myocardium. BACKGROUND: Segmental left ventricular (LV) dysfunction in the absence of coronary atherosclerosis is frequently seen in patients with chronic Chagas' heart disease. Myocardial ischemia and coronary microcirculation abnormalities have been found in animal models and in humans with Chagas' disease. In addition, chagasic sera may contain autoantibodies against human beta adrenergic receptors. METHODS: Two groups of patients with Chagas' disease were studied by echocardiography: group 1 (n = 12) without and group 2 (n = 14) with LV segmental wall motion abnormalities (mostly apical aneurysm). Ten normal subjects served as control subjects. We performed qualitative assessment of wall motion and quantitative evaluation of LV cavity under baseline conditions and after dobutamine stimulation. RESULTS: Patients with Chagas' disease exhibited a blunted inotropic and chronotropic response to dobutamine stimulation. After dobutamine, fractional area change in Chagas' group 1 (54.7+/-6.6%; SD) and in group 2 (35.1+/-12.1%) were significantly lower than control group (66.7+/-2.5%; p < 0.001). In addition, in 6 of 14 group 2 patients, dobutamine induced a biphasic response with improvement at low dose and deterioration at peak dose, as seen in patients with coronary artery disease. Although the three groups had similar basal mean heart rates and attained a similar mean peak dobutamine doses, both groups of patients with Chagas' disease had a significantly blunted mean heart rate effect after dobutamine (p < 0.0001). CONCLUSIONS: Thus, dobutamine stimulation unmasks a chronotropic incompetence and a blunted myocardial contractile response in chagasic patients, even in those with no overt manifestation of heart disease. PMID- 9973035 TI - Relationship between endothelin-1 extraction in the peripheral circulation and systemic vascular resistance in patients with severe congestive heart failure. AB - OBJECTIVES: This study was done to determine the spillover and extraction of endothelin-1 (ET-1) in the peripheral circulation, and to evaluate the factors that regulate local ET-1 extraction in the peripheral circulation in patients with congestive heart failure (CHF). BACKGROUND: The relationship between the spillover and extraction of the ET-1 in the peripheral circulation and systemic vascular resistance (SVR) has not been fully clarified. METHODS: We measured plasma levels of ET-1 both in femoral artery (FA) and femoral vein (FV) in 93 patients with CHF. RESULTS: Plasma ET-1 was significantly higher in FV than in FA in New York Heart Association (NYHA) functional class II patients, but there was no difference of ET-1 between FA and FV in functional class III patients. In patients with functional class IV, plasma ET-1 was significantly lower in FV than in FA, and SVR was significantly higher than in patients with NYHA class II or class III. Moreover, a significant positive correlation existed between plasma ET 1 extraction across the lower leg and SVR in these patients. Among the various neurohumoral factors and hemodynamics, plasma levels of ET-1, angiotensin II in the FA showed an independent and significant relationship with the plasma arteriovenous difference of ET-1 in the lower limb. CONCLUSIONS: Circulating ET-1 is extracted in peripheral circulation in patients with severe CHF, suggesting the possibility of upregulation of ET receptors of vascular beds in the lower limb in these patients. The peripheral extraction of ET-1 correlates with SVR in severe CHF patients and is mainly regulated by the local ET-1 and renin angiotensin systems. PMID- 9973036 TI - Mechanism of dynamic regurgitant orifice area variation in functional mitral regurgitation: physiologic insights from the proximal flow convergence technique. AB - OBJECTIVES: We used the Doppler proximal flow convergence technique as a physiologic tool to explore the effects of the time courses of mitral annular area and transmitral pressure on dynamic changes in regurgitant orifice area. BACKGROUND: In functional mitral regurgitation (MR), regurgitant flow rate and orifice area display a unique pattern, with peaks in early and late systole and a midsystolic decrease. Phasic changes in both mitral annular area and the transmitral pressure acting to close the leaflets, which equals left ventricular left atrial pressure, have been proposed to explain this dynamic pattern. METHODS: In 30 patients with functional MR, regurgitant orifice area was obtained as flow (from M-mode proximal flow convergence traces) divided by orifice velocity (v) from the continuous wave Doppler trace of MR, transmitral pressure as 4v(2), and mitral annular area from two apical diameters. RESULTS: All patients had midsystolic decreases in regurgitant orifice area that mirrored increases in transmitral pressure, while mitral annular area changed more gradually. By stepwise multiple regression analysis, both mitral annular area and transmitral pressure significantly affected regurgitant orifice area; however, transmitral pressure made a stronger contribution (r2 = 0.441) than mitral annular area (added r2 = 0.008). Similarly, the rate of change of regurgitant orifice area more strongly related to that of transmitral pressure (r2 = 0.638) than to that of mitral annular area (added r2 = 0.003). A similar regurgitant orifice area time course was observed in four patients with fixed mitral annuli due to Carpentier ring insertion. CONCLUSIONS: In summary, the time course and rate of change of regurgitant orifice area in patients with functional MR are predominantly determined by dynamic changes in the transmitral pressure acting to close the valve. Thus, although mitral annular area helps determine the potential for MR, transmitral pressure appears important in driving the leaflets toward closure, and would be of value to consider in interventions aimed at reducing the severity of MR. PMID- 9973037 TI - Doing away with dogma: increasing afterload to reduce mitral regurgitation. PMID- 9973038 TI - Cardiorespiratory responses to negative pressure ventilation after tetralogy of fallot repair: a hemodynamic tool for patients with a low-output state. AB - OBJECTIVES: We hypothesized that a period of cuirass negative pressure ventilation (NPV) would augment the cardiac output of patients in the early postoperative period after complete correction of tetralogy of Fallot (TOF). BACKGROUND: Diastolic right ventricular dysfunction can lead to a low-output state in an important minority of patients after TOF repair. In these patients, the diastolic pulmonary arterial flow, which characterizes restrictive right ventricular physiology, and on which the cardiac output is so dependent, is highly sensitive to changes in intrathoracic pressure. METHODS: The effects of NPV on pulmonary blood flow were investigated in 23 intubated children who were initially ventilated using intermittent positive pressure ventilation after TOF repair. Eight patients had restrictive right ventricular physiology. All children received a 15-min period of NPV, and eight received a prolonged period (45 min) of NPV. RESULTS: A brief period of NPV increased pulmonary blood flow by 39%, and the improvement further continued if the study period was extended, with a total increase of 67% after 45 min. Patients with restrictive physiology had a somewhat delayed response to NPV, but the ultimate increase during an extended period of NPV was greater in restrictive patients (84%) than nonrestrictive patients (50%). CONCLUSIONS: By manipulating important cardiopulmonary interactions, NPV improves the cardiac output of patients after TOF repair, and has a role as a hemodynamic tool in the management of the low-output state in selected cases. PMID- 9973040 TI - Upregulated expression of cardiac endothelin-1 participates in myocardial cell growth in Bio14.6 Syrian cardiomyopathic hamsters. AB - OBJECTIVES: The purpose of this study is to investigate the role of endogenous endothelin-1 (ET-1) in myocardial growth in Bio 14.6 Syrian cardiomyopathic hamsters (Bio). BACKGROUND: While ET-1, as a growth-promoting peptide, has been implicated in the development of secondary cardiac hypertrophy, the role of endogenous ET-1 in cardiac growth in primary myocardial disease is unknown. METHODS: We measured left ventricular ET-1 levels by a specific sandwich enzyme linked immunosorbent assay. Furthermore, we examined the chronic effect of T0201, an ET type A receptor-specific antagonist. RESULTS: The ET-1 levels in the left ventricles were 1.8-fold higher (p < 0.0005) at 20 weeks and 6.4-fold higher (p < 0.0001) at 35 weeks in the Bio compared to age-matched control F1B hamsters (F1B). The Bio ET-1 levels in the lungs exhibited an only 1.3-fold elevation at 35 weeks. Immunohistochemistry demonstrated the localization of ET-1 mainly in the cardiac myocytes. The treatment with T0201 significantly reduced the heart weight/body weight ratio in the Bio, but did not affect the heart weight/body weight ratio in the F1B. Histologically, T0201 reduced the myocyte diameter of Bio to a level similar with that of F1B. However, T0201 did not affect the extent of fibrosis in Bio or F1B. CONCLUSIONS: The ET-1 level in the heart of cardiomyopathic hamsters increases in stage-dependent and organ-specific manners. Though myocyte degeneration and subsequent replacement fibrosis do not require an ET-1 pathway, the accelerated synthesis of ET-1 in the heart may contribute to the pathological growth of remaining myocytes in this animal model. PMID- 9973039 TI - Renal ischemia/reperfusion remotely improves myocardial energy metabolism during myocardial ischemia via adenosine receptors in rabbits: effects of "remote preconditioning". AB - OBJECTIVES: This study examined the changes in myocardial energy metabolism during myocardial ischemia after "remote preconditioning" and investigated the involvement of adenosine receptors in the mechanisms of this effect. BACKGROUND: Recent studies have indicated that a brief period of ischemia and reperfusion (ischemic preconditioning, PC) in a remote organ reduces myocardial infarct size (IS) protecting against subsequent sustained myocardial ischemia. However, the mechanisms of "remote PC" remain unclear. We assessed myocardial energy metabolism during sustained myocardial ischemia and reperfusion after renal PC (RPC), in comparison with that after myocardial PC (MPC) in open-chest rabbits. It has been established that adenosine receptors are involved in the mechanisms of MPC. METHODS: Rabbits that had been anesthetized with halothane were divided into six groups. The control (CNT) group underwent 40-min coronary occlusion followed by 120 min reperfusion. Before the procedure, the MPC group underwent an additional protocol of 5 min coronary artery occlusion and 20 min reperfusion, and the RPC group received a 10 min episode of renal artery occlusion and 20 min reperfusion. In additional experimental groups, 8 sulfophenyl-theophylline (SPT, 10 mg/kg), an adenosine receptor inhibitor, was intravenously injected before the 40 min myocardial ischemia (SPT, MPC + SPT and RPC + SPT groups, respectively). Myocardial levels of phosphocreatine (PCr), ATP and intracellular pH (pHi) were measured by 31P-NMR spectroscopy. RESULTS: RPC and MPC delayed the decreases in ATP levels, preserved pHi during 40-min myocardial ischemia and resulted in better recovery of ATP and PCr during 120 min reperfusion compared with the controls. SPT abolished the improvement in myocardial energy metabolism and the reduction in myocardial IS caused by MPC or RPC. Myocardial IS in the CNT (n = 8), MPC (n = 9), RPC (n = 9), SPT (n = 6), MPC + SPT (n = 8) and RPC + SPT (n = 8) groups averaged 42.8+/-3.5%, 18.2+/-1.8%*, 19.6+/-1.3%*, 44.9+/-5.0%, 35.6+/ 2.7% and 34.8+/-3.6% of the area at risk (*p < 0.05 vs. CNT), respectively. CONCLUSIONS: PC in a remote organ, similar to MPC, improved myocardial energy metabolism during ischemia and reperfusion and reduced IS in vivo by an adenosine dependent mechanism in rabbits. PMID- 9973041 TI - Inotropic infusions for chronic congestive heart failure: medical miracles or misguided medicinals? PMID- 9973042 TI - Q-wave versus non-Q wave myocardial infarction: a meaningless distinction. AB - The whole subject can thus be summed up in two statements. 1. Every appropriately designed study comparing first Q and NQMI's has found no difference in post-MI course of the two categories and no foundation for the common notion that the NQMI is a uniquely "unstable" entity, to be classed with unstable angina in terms of prognosis and management. Nine such studies have been published. On the other hand, all studies alleging the "unstable" character of the NQMI have been invalidated by major flaws, chief among them the comparison of undifferentiated mixtures of first and subsequent infarcts with widely differing mortality and morbidity. This confusion is further compounded by the fact that subsequent infarcts generate Qwaves less than half as often as first infarcts. 2. All current studies indicate that there is no benefit to an invasive as compared with a conservative protocol for management of NQMI. Since the characterization of an infarct as "non-Q' conveys no therapeutic implications, the classification becomes irrelevant and should be discarded. Two quotations sum the whole matter succinctly. Moss (63) commented that "The Q-wave versus non-Q-wave categorization does not provide sufficient sensitivity, specificity, or predictive accuracy about the subsequent clinical course of patients with a first myocardial infarction to use it as reliable data in the clinical decision-making process." Surawicz (64) put the matter even more concisely: ". . . a non-Qwave MI is not a unique entity: rather it is a smaller and less extensive MI." In a word, the magnitude of a myocardial infarction should be judged on anatomical and functional considerations rather than on the designation of Qwave versus non Qwave infarction. PMID- 9973043 TI - Do you believe in God? PMID- 9973044 TI - Echocardiography in emergency medicine: a policy statement by the American Society of Echocardiography and the American College of Cardiology. Task Force on Echocardiography in Emergency Medicine of the American Society of Echocardiography and the Echocardiography and Technology and Practice Executive Committees of the American College of Cardiology. PMID- 9973045 TI - Is acute rest scintigraphic myocardial perfusion imaging in patients with acute chest pain and nondiagnostic electrocardiograms clinically useful, or is it misleading? PMID- 9973046 TI - Plasma lipoprotein(a) and severity of angiographic coronary artery disease. PMID- 9973047 TI - Peak VO2 et al. for prognosis in heart failure? PMID- 9973048 TI - An analysis of blood management in patients having a total hip or knee arthroplasty. AB - Three hundred and thirty orthopaedic surgeons in the United States participated in a study of transfusion requirements associated with total joint arthroplasty. A total of 9482 patients (3920 patients who had a total hip replacement and 5562 patients who had a total knee replacement) were evaluated prospectively from September 1996 through June 1997. Of those patients, 4409 (46 percent [57 percent of the patients who had a hip replacement and 39 percent of the patients who had a knee replacement]) had a blood transfusion. Two thousand eight hundred and ninety patients (66 percent) received autologous blood, and 1519 patients (34 percent) received allogenic blood. Ordered logistic regression analysis showed the most important predictors of the transfusion of allogenic blood to be a low baseline hemoglobin level and a lack of predonated autologous blood. Preoperative donation of autologous blood decreases the risk of transfusion of allogenic blood; however, inefficiencies in the procedures for obtaining autologous blood were identified. Sixty-one percent (5741) of the patients had predonated blood for autologous transfusion, but 4464 (45 percent) of the 9920 units of the predonated autologous blood were not used. Primary procedures and revision total knee arthroplasty were associated with the greatest number of wasted autologous units. Of the 5741 patients who had predonated blood, 503 (9 percent) needed a transfusion of allogenic blood. The frequency of allogenic blood transfusion varied with respect to the type of operative procedure (revision total hip arthroplasty and bilateral total knee arthroplasty were associated with the highest prevalence of such transfusions) and with a baseline hemoglobin level of 130 grams per liter or less. Transfusion of allogenic blood was also associated with infection (p < or = 0.001), fluid overload (p < or = 0.001), and increased duration of hospitalization (p < or = 0.01). These latter findings warrant further evaluation in controlled studies. PMID- 9973049 TI - Interposition of the split flexor hallucis longus tendon after resection of a coalition of the middle facet of the talocalcaneal joint. AB - Ten consecutive patients (fourteen feet) who had a painful coalition of the middle facet of the talocalcaneal joint with restricted motion of that joint were managed with a resection of the coalition and interposition of a split flexor hallucis longus tendon in 1992, 1993, or 1994. Initial nonoperative treatment of all of the feet had failed. According to the ankle-hindfoot clinical rating system of the American Orthopaedic Foot and Ankle Society, there were eleven excellent results and one good, one fair, and one poor result at a mean of fifty one months (range, thirty-two to sixty months) after the procedure. Thirteen of the fourteen procedures resulted in considerable relief of pain, an improved range of motion of the talocalcaneal joint, and improved function of the foot. No patient had symptoms or functional impairment of the great toe secondary to the interposition of the split flexor hallucis longus tendon. On the basis of these early results, tendon interposition appears to be an excellent procedure for the treatment of a symptomatic coalition of the middle facet of the talocalcaneal joint after initial nonoperative treatment has failed. The presence of degenerative osteoarthritis in the other facets of the talocalcaneal joint is a contraindication to this procedure. The long-term results have yet to be determined. However, the standardized rating system used in the present study will allow accurate comparison of our results with those of subsequent studies. PMID- 9973050 TI - Complete traumatic brachial plexus palsy. Treatment and outcome after repair. AB - Seventy-eight patients who had a complete brachial plexus palsy caused by a stretching injury were operated on by the same surgeon between January 1980 and December 1991. The aim of the operative intervention was to obtain the best functional result, including at the level of the hand, that was possible in view of the initial lesions and the intraoperative findings. Therefore, the treatment strategy included not only nerve repair with grafting (124 grafts) or nerve transfer (twenty-seven transfers) but also palliative procedures, the latter of which sometimes were performed several years later. Sixty-three patients were evaluated by an independent observer at least three years postoperatively. The results associated with each type of lesion and each type of nerve repair were assessed according to the function of the muscles that were innervated by the recipient nerve. Six patients had a neurolysis only. The remaining fifty-seven patients had grafts or nerve transfers to repair the biceps. Thirty-six of the fifty-seven received a rating of 3+ or more (meaning that the patient was able to flex the elbow repeatedly); the remaining twenty-one received a rating of 3 or less (meaning that the patient was able to flex the elbow only once or not at all), which we considered unsatisfactory. The function of the triceps recovered after eleven of thirty-one procedures that were performed to restore that nerve; that of the extensor carpi radialis, after five of thirty-one procedures; that of the flexor carpi radialis, after six of thirty-one procedures; and that of the flexor digitorum, after four of thirty-one procedures. A statistical analysis revealed that an operative delay of less than six months was a significant factor with respect to recovery of the function of the biceps (p = 0.003). The thirty nine grafts that were sutured onto the lateral or posterior cord produced better results than did the thirty-six that were sutured onto the distal branches (the musculocutaneous and radial nerves); however, with the numbers available, this difference was not found to be significant (p = 0.08). Eleven patients had a successful result (a rating of 3+ or more) and eight, a fair or poor result, with respect to recovery of biceps function after transfer of the spinal accessory nerve to the musculocutaneous nerve. Overall, twenty-nine patients had relief of pain postoperatively. Sixteen patients had grade-3 pain preoperatively compared with only three after the operation. According to a self-rating scale, twenty five patients were satisfied with the overall result, sixteen were fairly satisfied, and twenty-two were dissatisfied. PMID- 9973051 TI - Isolation and characterization of polyethylene wear debris associated with osteolysis following total shoulder arthroplasty. AB - We evaluated the interface membranes surrounding three total shoulder prostheses that had been removed because of progressive aseptic loosening associated with osteolysis. The mean time between the uncomplicated initial arthroplasty and the revision procedure was twelve years (10.5, 10.5, and 16.0 years). Membranes from around both the humeral and the glenoid component were obtained from all three shoulders and were studied histologically to determine the biological response involved in the development of aseptic loosening. For the purpose of comparison, periprosthetic tissue was also obtained from the sites of four failed total hip prostheses that were associated with osteolysis. Polyethylene particles were retrieved with an enzymatic digestion technique that involved the use of papain. Raman vibrational spectroscopy verified that the particles were ultra-high molecular weight polyethylene. The particles were isolated from the tissue, and a computerized image-analysis system characterized 582 of them in terms of size and morphology. Each particle was defined with the use of six shape descriptors: equivalent circle diameter, roundness, form factor, aspect ratio, elongation, and outline fractal dimension. The particles from the hips had a mean equivalent circle diameter (and standard error of the mean) of 0.62 +/- 0.03 micrometer, were predominantly globular in shape, and had low mean values for aspect ratio (1.46 +/- 0.02) and elongation (1.85 +/- 0.03) and relatively high values for roundness (0.74 +/- 0.01) and form factor (0.87 +/- 0.01). In contrast, the particles from the shoulders had a mean equivalent circle diameter of 1.04 +/- 0.03 micrometers. In addition, they had relatively high values for aspect ratio (2.36 +/- 0.07) and elongation (4.96 +/- 0.23) and correspondingly low values for roundness (0.54 +/- 0.01) and form factor (0.67 +/- 0.01), indicating that they were more fibrillar in shape. The particles from the shoulders and those from the hips were significantly different (p < 0.0001) with respect to all of the descriptors except outline fractal dimension. The particles from the shoulders, in general, were larger and more fibrillar than the particles from the hips. PMID- 9973052 TI - Instability of the elbow treated with semiconstrained total elbow arthroplasty. AB - The results of nineteen semiconstrained modified Coonrad-Morrey total elbow arthroplasties performed in nineteen patients to treat instability were evaluated at an average of seventy-two months (range, twenty-five to 128 months) postoperatively. Preoperatively, all patients had either a flail elbow or gross instability of the elbow that prevented useful function of the extremity. The instability of sixteen elbows was the result of a traumatic injury or of the treatment of such an injury. The most recent result was satisfactory for sixteen elbows and unsatisfactory for three. The average overall Mayo elbow performance score increased from 44 points preoperatively to 86 points postoperatively. At the most recent follow-up examination, no elbow was unstable. The average arc of flexion was from 25 degrees (range, 0 to 60 degrees) to 128 degrees (range, 30 to 142 degrees), which represented a 58-degree increase from the preoperative average arc. Sixteen patients had little or no pain after the arthroplasty. There were four complications in four patients. Three complications (loosening of the humeral component in one patient and a fracture of the ulnar component in two) occurred postoperatively; all three were treated with a revision procedure. The other complication (a fracture of the olecranon) occurred intraoperatively and was treated with tension-band fixation; the most recent outcome was not affected. Radiographically, one patient had complete (type-V) radiolucency about the humeral component. None of the nine patients for whom true anteroposterior radiographs were available had evidence of wear of the bushings. The bone graft behind the anterior flange of the humeral prosthesis was mature in fourteen elbows, incomplete in two, and resorbed in two. One patient was excluded from this analysis because radiographs were not available. Instability of the elbow resulting in the inability to use the extremity is a challenging clinical situation. However, in patients who are more than sixty years old and in selected patients who are less than sixty years old but who have extensive loss of bone as a result of severe injury, have had multiple operations, or have rheumatoid arthritis, total elbow arthroplasty with a linked, semiconstrained prosthesis reestablishes a mobile, stable joint without premature loosening or failure of the components. In our experience, the use of customized implants, maintenance of the muscular attachments to the epicondyles, and reconstruction of the epicondyles to the implant were unnecessary. PMID- 9973053 TI - Results of Herbert-screw fixation with bone-grafting for the treatment of nonunion of the scaphoid. AB - We examined twenty-one patients in whom an established nonunion of the scaphoid had been treated with Herbert-screw fixation with bone-grafting; our purpose was to determine the long-term morbidity of the procedure (at an average of forty eight months; range, seventeen to fifty-five months). According to the modified scaphoid outcome scoring system, eighteen patients had a good or excellent result. No patient had failure of the hardware. Radial deviation was significantly decreased (an average of 17 degrees; 55 percent) compared with that of the contralateral wrist (p = 0.02). The other ranges of motion and the grip strength were also decreased, although the difference was not found to be significant with the numbers available. Three patients had a persistent nonunion, and two of them also had loosening of the hardware. Three patients had a tender hypertrophic scar. On the basis of our data, we concluded that Herbert-screw fixation with bone-grafting is effective for the treatment of nonunion of the scaphoid. PMID- 9973054 TI - Load-displacement behavior in a distal radial fracture model. The effect of simulated healing on motion. AB - External fixation of fractures of the distal end of the radius neutralizes external forces and maintains axial alignment during healing. As far as we know, there have been no biomechanical studies of the effects of early removal of the fixator in a partially healed fracture model. The purpose of the present study was to observe the load-displacement behavior of a distal radial fracture model in which we had simulated partial healing by injection of butyl-rubber caulk and augmented this simulated healing with Kirschner-wire fixation. Sixteen fresh frozen hand-wrist-forearm specimens from cadavera were mounted in mid-rotation in resin pots, and a load was applied. An osteotomy was used to simulate the fracture. Relative motion at the site of the osteotomy was compared, with use of a three-dimensional Optotrak kinematic device, during physiological loading of six constructs with Kirschner-wire transfixion or outrigger fixation. In the experimental group, partial healing was simulated by injection of butyl-rubber caulk into the site of the osteotomy and testing with simulated muscle-loading was performed through a full range of motion of the wrist. No difference could be detected between the relative motion at the osteotomy sites that had been treated with standard fully augmented external fixation and that in the experimental group (p > 0.05). T test analysis revealed that motion was equivalent regardless of whether Kirschner-wire transfixion or outrigger fixation had been used (p = 0.62) and that all of the augmented constructs had significantly less relative motion than all of the nonaugmented constructs (p < 0.001). PMID- 9973055 TI - Acetabular involvement in osteonecrosis of the femoral head. AB - When an arthroplasty is needed to treat osteonecrosis of the femoral head, the use of a component that replaces or resurfaces only the femoral head is often considered as an alternative to total hip replacement if the acetabulum appears radiographically normal. However, the long-term results of the use of endoprostheses have often been poor, secondary in part to progressive degeneration of the acetabular cartilage and to protrusio acetabuli. To help to explain these observations, we examined the acetabular cartilage in forty-one hips in which a primary total hip replacement had been performed because of osteonecrosis of the femoral head in association with a radiographically normal acetabulum. The cartilage in the superior, weight-bearing region of the acetabulum was grossly abnormal in forty of the forty-one hips and it was histologically abnormal in all thirty-three hips that were so evaluated. In all but one hip, gross degeneration of the cartilage was apparent, involving less than 20 percent of the acetabulum; the degeneration was graded as mild (superficial fibrillation and slight irregularity of the surface) in sixteen hips, moderate (moderate fibrillation, alteration in color and consistency, and thinning of cartilage without complete erosion to bone) in twenty hips, and severe (marked fibrillation, alteration in color and consistency, and marked thinning of cartilage with areas of complete erosion to bone) in four hips. These observations emphasize the fact that radiographs cannot demonstrate early degeneration of cartilage and that, by the time that an arthroplasty is needed, degenerative changes are already present in the acetabular cartilage of a high percentage of hips with osteonecrosis, even when radiographs of the acetabulum show no abnormalities. These findings should be kept in mind when a decision is being made regarding which type of arthroplasty should be done in a patient who has osteonecrosis of the femoral head and regarding when to do the procedure. PMID- 9973056 TI - The Harris-Galante porous-coated acetabular component with screw fixation. An average ten-year follow-up study. AB - Two hundred and thirty-seven consecutive primary acetabular reconstructions were performed, in 213 patients, with use of a Harris-Galante porous-coated acetabular component with screw fixation between January 1984 and December 1987. Twenty-four patients (twenty-seven hips) died before a minimum duration of follow-up of eighty-four months, five patients (five hips) were too ill to return for a detailed follow-up examination at the time of the study, four patients (four hips) refused clinical and radiographic follow-up (but one of these patients had more than eighty-four months of follow-up for one side of a bilateral total hip replacement), two patients (two hips) were lost to follow-up, and two patients (two hips) refused radiographic follow-up but had adequate clinical follow-up. In addition, one patient who had had a bilateral total hip replacement had a resection arthroplasty on one side because of a late infection 115 months after the index procedure. Thus, 196 hips (83 per cent) in 177 patients were available for radiographic and clinical review after an average duration of follow-up of 122 months (range, eighty-four to 155 months). The average age of these 177 patients at the time of the operation was fifty-nine years (range, twenty-three to eighty-seven years). Eight well fixed acetabular shells (4 percent) were revised: three were revised because of dissociation of the liner in association with fractures of the tines, three were revised during revision of the femoral component, and two were revised because of retroacetabular osteolysis. In eight other hips, the acetabular liner was exchanged during revision of a loose femoral component. No acetabular component migrated, was classified as radiographically loose, or was revised because of aseptic loosening. There was no evidence of fragmentation or disruption of the titanium porous mesh of any cup. One of 528 screws broke. There were no complications associated with the insertion of the acetabular fixation screws. Osteolytic lesions were identified adjacent to nine (5 percent) of the 188 acetabular components that were in place at the time of the most recent examination. One hip, which had discontinuous osteolytic lesions in all three acetabular zones, was treated with bone-grafting around the well fixed acetabular component. Eight hips had a discontinuous radiolucent line that was 1.0 millimeter wide or less in all three zones and another two had a continuous radiolucent line that was 0.5 millimeter wide in all three zones. The average Harris hip score for the 188 hips (169 patients) that did not have revision of the acetabular shell improved from 47 points (range, 22 to 71 points) preoperatively to 89 points (range, 35 to 100 points) at the time of the latest examination. One hundred and thirty-four hips had an excellent result; twenty six, a good result; nineteen, a fair result; and nine, a poor result. All nine hips that had a poor result were in patients who had other factors, unrelated to the acetabular component, that contributed to the low Harris hip score. In the present study, the Harris-Galante porous-coated acetabular component continued to provide excellent fixation and clinical results for most patients at an average of approximately ten years after the operation. PMID- 9973057 TI - The porous-coated anatomic total hip prosthesis, inserted without cement. A prospective study with a minimum of ten years of follow-up. AB - One hundred consecutive primary total hip arthroplasties performed with use of a porous-coated anatomic total hip prosthesis, fixed without cement, in ninety-one patients were followed prospectively for a minimum of ten years. At the time of the most recent follow-up, twenty patients (twenty-three hips) had died and seventy-one patients (seventy-seven hips) were living. The average age of the living patients was sixty-six years (range, thirty-two to ninety-two years), and their average Harris hip score was 84 points (range, 33 to 100 points). Twelve percent (nine) of the seventy-seven hips were found to be associated with pain in the thigh when the patients were specifically questioned by the examiner. Eleven hips were revised during the follow-up period. Only the acetabular component was revised in six hips, only the femoral component was revised in one hip, and both the femoral and the acetabular components were revised in four hips. Of the ten acetabular revisions, one was performed because of acute dissociation of the component and eight, because of a combination of polyethylene wear, osteolysis, and loosening; the tenth acetabular revision consisted of exchange of the liner and curettage and bone-grafting of the osteolytic area. Of the five femoral revisions, two were performed because of loosening and three, because of extensive osteolysis of the proximal aspect of the femur. Including the revised components, twelve acetabular components and five femoral components had radiographic evidence of aseptic loosening. Acetabular osteolysis occurred in seventeen hips. Femoral osteolysis occurred in thirty-nine hips: in the proximal aspect of thirty-one hips, in the distal aspect of four, and in both the proximal and the distal aspect of four. The durability of the femoral fixation documented in this study is especially encouraging in view of the fact that this was our initial experience with devices fixed without cement and that a so-called first generation femoral component was used. However, the study also demonstrated that not all acetabular components fixed without cement function well over the long term and that specific design considerations (adequate initial fixation, congruency between the liner and the shell, an optimum shell-liner capturing mechanism, and a smaller femoral head) are warranted. PMID- 9973058 TI - Medial protrusio technique for placement of a porous-coated, hemispherical acetabular component without cement in a total hip arthroplasty in patients who have acetabular dysplasia. AB - Twenty-four hip replacements were performed with use of a medial protrusio technique to stabilize the fit of a hemispherical metal shell in the acetabulum in nineteen patients who had dysplasia of the hip. All of the hips were followed for a minimum of five years (average, seven years; range, five to thirteen years). Six of the hips were type I, seven were type II, eight were type III, and three were type IV according to the criteria of Crowe et al. The acetabular cup was implanted with the medial aspect of its dome beyond the Kohler line (drawn from the ischium along the ilioischial line) in all hips. An autogenous graft sculpted from the femoral head was used to cover 15 to 30 percent of the superolateral portion of the cup in one type-I hip, four type-III hips, and one type-IV hip. The need for these six bone grafts could have been avoided by reaming two to three millimeters more medially or by allowing 20 percent of the superolateral portion of the cup to be uncovered. Sixty to 84 percent of each bone graft was resorbed, effectively leaving the superolateral portion of the cup uncovered. The amount of the surface of the cup that was beyond the Kohler line averaged 41 percent for the six type-I hips, 43 percent for the seven type-II hips, 41 percent for six of the type-III hips, and 44 percent for one of the type IV hips. Crossing of the ilioischial and iliopubic lines was noted on the radiographs of two type-III and two type-IV hips. Radiographs of two type-I hips and one type-II hip showed 7 to 17 percent of the surface of the dome of the cup through the internal pelvic wall (beyond the iliopubic line). None of the twenty four metal shells were revised. A reoperation was performed on two hips to exchange a worn polyethylene insert, and three femoral components that had been fixed without cement were revised because of mechanical loosening. Wear averaged 0.26 millimeter per year in the fourteen hips that had a titanium femoral head and 0.09 millimeter per year in the nine hips that had a cobalt-chromium femoral head. The remaining hip had a ceramic femoral head, and the wear rate was 0.09 millimeter per year. The medial protrusio technique is a predictable, reproducible method for obtaining fixation of a porous-coated, hemispherical acetabular component in a dysplastic acetabulum. The technique permits the use of a porous-coated (bone-ingrowth) component; avoids the use of support bone graft and thereby reduces the operative time; facilitates rehabilitation by permitting earlier weight-bearing of the hip; and permits the use of a modular bearing surface, which may allow future exchange of only this surface rather than revision of the entire acetabular component because of excessive wear. PMID- 9973059 TI - Effect of flexibility of the femoral stem on bone-remodeling and fixation of the stem in a canine total hip arthroplasty model without cement. AB - The purpose of this study was to compare, with regard to fixation of the implant and femoral bone resorption, two fully porous-coated stems of different stiffnesses in a canine total hip arthroplasty model. A bilateral arthroplasty was carried out with insertion of a titanium-alloy stem (which had stiffness properties comparable with those of the canine femur) on one side and with insertion of a composite stem (which was three to fivefold more flexible than the canine femur) on the contralateral side. Eight femora were evaluated at six months and eight, at eighteen months after the operation, to determine the extent of bone ingrowth, periprosthetic cortical area, intracortical porosity, and bone remodeling. Despite the markedly greater flexibility of the composite stems, no significant difference could be detected (with the numbers available), with regard to the overall degree of femoral stress-shielding, cortical area, or cortical porosity, between these stems and the stiffer, titanium-alloy stems at either time-period. However, the composite stems had less bone ingrowth and more formation of radiopaque lines than did the titanium-alloy stems. At eighteen months, the values for bone ingrowth were 9.7 +/- 5.38 percent (mean and standard deviation) for the composite stems compared with 28.1 +/- 5.31 percent for the titanium-alloy stems (p = 0.003). Furthermore, the histological sections from the femora containing a composite stem showed radiopaque lines indicative of fibrous ingrowth approximately threefold more often than did those from the femora containing a titanium-alloy stem (p = 0.02). PMID- 9973060 TI - Paradoxical cerebral embolism complicating a major orthopaedic operation. A report of two cases. PMID- 9973061 TI - Fracture-dislocation of the lumbar spine after arthrodesis with instrumentation for idiopathic scoliosis. PMID- 9973063 TI - Current concepts review. Methods for locating missing patients for the purpose of long-term clinical studies. PMID- 9973062 TI - Wear in total hip and knee replacements. PMID- 9973064 TI - The utility of histological examination of tissue removed during elective joint replacement. A preliminary assessment. PMID- 9973065 TI - The utility of histological examination of tissue removed during elective joint replacement. A preliminary assessment. PMID- 9973066 TI - The utility of histological examination of tissue removed during elective joint replacement. A preliminary assessment. PMID- 9973067 TI - Ecological analysis of intended treatment effects: caveat emptor. PMID- 9973068 TI - Uses of ecologic studies in the assessment of intended treatment effects. AB - Because of the potential for confounding by indication (disease severity) in individual-level observational studies of intended treatment effects, a treatment designed to prevent an adverse event may appear to cause it. We use a hypothetical example to show that despite substantial variation in the frequency of treatment among patients residing in different geographic areas, a constant area-specific mortality rate can be observed, indicating the absence of confounding by indication at the ecologic level. The advantage of ecologic over individual-level observational studies in the assessment of intended treatment effects holds even if variations in disease severity, socioeconomic status, and other unmeasured factors are taken into account, as long as treatment utilization is influenced by practice style in the local medical community independently of disease severity. Ecologic studies can suggest the need for changes in practice, help resolve ethical issues, and indicate priorities for randomized trials. PMID- 9973069 TI - Abstruse comparisons: the problems of numerical contrasts of two groups. AB - The most common quantitative comparison in medical literature is a contrast of two numbers, such as two means or two rates. The two numbers, A and B, can be compared as a direct increment (A-B), ratio (A/B), relative change ([A-B]/B), or other index of contrast. To appreciate the quantitative distinction, a reader must know the "setting" reflected by the basic values of A and B. For example, a ratio of 2.0 does not distinguish comparisons between rates of 60% versus 30% and 0.006% versus 0.003%. Despite the frequency of published comparisons, they can be expressed with two types of abstrusity: quantitatives, if the basic values for A and B are not readily evident; and qualitative, if the component underlying variables are unfamiliar and not suitably explained. Among the published articles during the first six months of 1995 for JAMA and New England Journal of Medicine, 57 that satisfied inclusion criteria were reviewed for compliance with standards for avoiding the two types of abstrusity. The standards for quantitative abstrusity were applied to the published abstract-summary, because it is often the only "sound bite" that is read and remembered by most readers. The standards for qualitative abstrusity, however, could be fulfilled in the text, not just in the abstract-summaries of each article. Among the 57 abstract-summaries, 30% were abstruse quantitatively, and 11 (48%) of 23 pertinent papers were qualitatively abstruse. Abstrusity can be eliminated if authors and editors insist that quantitative contrasts cite the basic numbers being compared and the meaning of the associated variables and their rating scales. PMID- 9973070 TI - Stratified randomization for clinical trials. AB - Trialists argue about the usefulness of stratified randomization. For investigators designing trials and readers who use them, the argument has created uncertainty regarding the importance of stratification. In this paper, we review stratified randomization to summarize its purpose, indications, accomplishments, and alternatives. In order to identify research papers, we performed a Medline search for 1966-1997. The search yielded 33 articles that included original research on stratification or included stratification as the major focus. Additional resources included textbooks. Stratified randomization prevents imbalance between treatment groups for known factors that influence prognosis or treatment responsiveness. As a result, stratification may prevent type I error and improve power for small trials (<400 patients), but only when the stratification factors have a large effect on prognosis. Stratification has an important effect on sample size for active control equivalence trials, but not for superiority trials. Theoretical benefits include facilitation of subgroup analysis and interim analysis. The maximum desirable number of strata is unknown, but experts argue for keeping it small. Stratified randomization is important only for small trials in which treatment outcome may be affected by known clinical factors that have a large effect on prognosis, large trials when interim analyses are planned with small numbers of patients, and trials designed to show the equivalence of two therapies. Once the decision to stratify is made, investigators need to chose factors carefully and account for them in the analysis. PMID- 9973071 TI - Association of comorbidity with disability in older women: the Women's Health and Aging Study. AB - There is substantial evidence that physical disability results from chronic diseases and that the number of chronic diseases is associated with the presence and severity of disability. There is some evidence that interactions between specific diseases are of import in causing disability. Beyond arthritis, however, little is known of the disease pairs that may be important to focus on in future research. This study explores the associations between multiple disease pairs and different types of physical disability, with the objective of hypothesis development regarding the importance of disease interactions. The study population comprised a representative sample of 3841 women 65 years and older living in Baltimore, screened for participation in the Women's Health and Aging Study. The study design was cross-sectional. An interviewer-administered screening questionnaire was administered regarding self-reported physical disability in 15 tasks of daily life, history of physician diagnosis of 14 chronic diseases, and MiniMental State examination. Task difficulty was empirically grouped into six subsets of minimally overlapping disabilities, with a comparison group consisting of those with no difficulty in any task subset. Multiple logistic regression models were fit assessing the relationship of major chronic diseases and of interactions of disease pairs with each disability subtype and with any disability, adjusting for confounders. Fourteen percent of the population reported mobility difficulty only; 5%, upper extremity difficulty only; 9%, both of these difficulties but no others; 7%, difficulty in higher function but not self-care tasks; 7%, self-care task difficulty but not higher function tasks; and 15%, difficulty in both higher function and self-care (weighted data). Almost all in the latter three groups had difficulty, as well, in mobility or upper extremity tasks. In regression models, specific disease pairs were synergistically associated with different types of disability. For example, important disease pairs that recurred in their associations with different disability types were the presence of arthritis and visual impairments, arthritis and high blood pressure, heart disease and cancer, lung disease and cancer, and stroke and high blood pressure. In addition, the type of disability that a disease was associated with varied, depending on the other disease that was present. Finally, when interactions were accounted for, many diseases were no longer, in themselves, independently associated with a given type of disability. Partitioning disability into six subtypes was more informative in terms of associations than was evaluating a summary category of "any disability." These findings provide a basis for further hypothesis development and testing of synergistic relationships of specific diseases with disabilities. If testing confirms these observations, these findings could provide a basis for new strategies for prevention of disability by minimizing comorbid interactions. PMID- 9973072 TI - A research registry: uses, development, and accuracy. AB - Many studies of population health, clinical epidemiology, and health services can be supported by a population-based research registry. Such a registry accurately defines the health insurance status for each individual over many years, magnifying the effectiveness of a cross-sectional registry (typically relevant for only a short duration) used in the administration of a health insurance plan. A research registry can distinguish between "well" individuals (no contact with the health care system), loss to follow-up (ineligibility associated with leaving the insurance plan), loss of continuity (two or more unlinked registrations over time for the same person), and mortality. The Manitoba research registry was developed to facilitate longitudinal studies; working within strict confidentiality controls, identifiers for each individual known to Manitoba Health since 1970 can be retrieved and a single unique identifier assigned. Careful reporting of changes in family registration numbers has enabled tracing area of residence, marital status, and family characteristics; results are equivalent to a daily census of the province. This article provides details on source materials, design, and quality of the registry, highlighting its value both for the development of integrated population health information systems and for research in general. PMID- 9973073 TI - Identifying adults at low risk for significant hyperlipidemia: a validated clinical index. AB - The objective of this study was to develop and validate a simple clinical index to identify individuals at increased risk of an elevated CHL/HDL ratio. Using recursive partitioning, factors associated with an elevated CHL/HDL ratio were identified among 1993 men and 1631 women in the Lipid Research Clinic Prevalence Study. These factors were weighted using logistic regression analyses to develop a clinical index that was validated on 486 men and 484 women reported in the Sante Quebec cardiovascular health survey. A high CHL/HDL ratio was defined as > or =5 for women and > or =6 for men which approximates the 75th percentiles reported in the second United States National Health and Nutrition Survey. In the Lipid Research Clinics cohort, 307 men (15.4%) and 188 women (11.5%) had an elevated CHL/HDL ratio. Using separate clinical indices for men and women, significant variables included body mass index, alcohol consumption, age, smoking status, systolic blood pressure, physical activity status, and the presence of diabetes, the study identified 88% of the men and 82% of the women with elevated ratios. External validation using the Sante Quebec data set demonstrated test sensitivities of 81% for men and 94% for women. Overall, 12% of those with a high CHL/HDL ratio were misclassified as low risk. The ratio of total plasma cholesterol to HDL cholesterol has been shown to be one of the best lipid predictors of increased coronary risk. Readily available clinical data can be used to identify 88% of those individuals most likely to benefit from lipid screening while obviating the need for such screening in one quarter of otherwise healthy adults. PMID- 9973074 TI - Patients with newly diagnosed carcinoma of the breast: validation of a claim based identification algorithm. AB - The objectives of this study were to validate a claims-based algorithm for identification of patients with newly diagnosed carcinoma of the breast and to optimize the algorithm. Claims data from all females aged 21 years or older who enrolled in a large California health maintenance organization during the study period from October 1, 1994 through March 31, 1996 were analyzed. Medical records of the patients identified through the claims-based algorithm were reviewed to determine whether the patients were correctly identified. The initial algorithm had a positive predictive value of 84% which was similar to the previous study. The percentages of correct identification significantly increased with the patient's age at diagnosis. Other patient demographic characteristics and facility characteristics were not related to the accuracy of the identification. Using a classification tree procedure and additional information from the false positive cases, the initial algorithm was modified for improvement. The best modified algorithm had a positive predictive value of 92% while only 0.5% (4/837) of the true-positive cases were excluded. The results once again demonstrated that patients with newly diagnosed carcinomas of the breast can be identified using claims data. These databases provide an efficient and effective tool for performing health services studies on large patient populations. PMID- 9973075 TI - Validity and utility of patient-reported health measures on hospital admission. AB - Patient perceptions of their health are often inadequately captured and explored on hospital admission where physiologic and other objective measures are the focus of attention. Therefore, we conducted a prospective study to develop and validate measures of several domains of patient-reported health status at the time of admission to a general medicine inpatient service, and to determine the value of these new measures in predicting length of stay (LOS). Within 2 hours of the time that a decision to admit a patient was made, research assistants delivered a structured interview that captured patients' current symptoms, functional status, mood, and perceived health. Interviews were conducted between 8 a.m. and 11 p.m., 5 days per week from July 1996 through June 1997. During this time, there were 3621 unique patients admitted to the medicine service; 2672 (74%) of these patients were eligible for an interview. Eighty-eight percent of the 2672 eligible patients were interviewed. In addition to the patient-reported measures captured through the structured interview, the acute physiology score (APS) of the APACHE II was calculated for all subjects. The internal consistency (i.e., Cronbach's alpha) of the scales was 0.76 or greater and concurrent validity (i.e., correlation) of the patient-reported measures with the APS was 0.01 to 0.13. Overall perceived health was correlated 0.20 to 0.45 with symptoms and functional status, and was correlated 0.07 with the APS. The patient-reported measures performed comparably to the APS in predicting LOS (R-square = 0.08). When the patient-reported measures and the APS were included in the same model, the R-square was 0.14. These analyses suggest that patient-reported measures of health and function on admission hold validity, and that responses to as few as 15 questions can provide data that may help to explain differences in length of a hospital stay. PMID- 9973076 TI - Validity of a self-reported history of doctor-diagnosed angina. AB - The objective of this study was to assess the validity of a self-reported history of doctor-diagnosed angina in population-based studies in men. Subjects were 5789 men from the British Regional Heart Study who reported being without an angina diagnosis at entry (1978-1980) and were alive at the end of 1992, aged 52 to 75 years. In 1992, subjects were asked in a self-administered questionnaire if they recalled ever having had a doctor diagnosis of angina. Self-report of diagnosed angina was compared with general practice (GP) record of angina obtained from reviews of medical records from study entry to the end of 1992. Men were followed for a further 3 years from 1992 for major ischemic heart disease events. The prevalence of diagnosed angina in 1992 was 10.1% according to self-reported history and 8.9% according to GP record review. There was substantial agreement between the two sources of information: 80% of men with a GP record of angina reported their diagnosis, and 70% of men who reported an angina diagnosis had confirmation of this from the record review. When all ischemic heart disease (angina or myocardial infarction) was considered, agreement was higher. Genuine angina was likely in many of the 177 men who had self-reported angina not confirmed by the GP record review: 78 had an ischemic heart disease history (myocardial infarction or coronary revascularization) identified by the review, and 31 had a GP record of angina after 1992. Angina symptoms, nitrate use, cardiological investigation, and surgical intervention for angina compared between agreement groups showed a very consistent pattern. All these indicators of angina were most common in men with both self-report and GP record of angina, least common in men with neither self-report nor GP record of angina, but had a substantially higher prevalence in men with self-reported angina only than in those with GP-recorded angina only. After 3 years follow-up from 1992, 9.5% of men with both self-report and GP record of angina, and 11.3% of men with self reported angina only had experienced a new major ischemic heart disease event; compared to 5.7% of men with a GP record of angina only and 2.7% of those without angina by either criteria. This pattern of risk remained similar after adjustment for age and previous myocardial infarction. These results suggest that self reported history of a doctor diagnosis of angina is a valid measure of diagnosed angina in population-based studies in men. PMID- 9973077 TI - Comparing participants and nonparticipants in a smoking cessation trial: selection factors associated with general practitioner recruitment activity. AB - We studied the relationship between smokers' sociodemographic characteristics, their smoking habit, health status, and the probability of their having been approached for recruitment in the smoking cessation trial performed in Turin, Italy, with the aim of gathering information on the role of selection criteria adopted by general practitioners (GPs) in offering anti-smoking counseling. The 965 smokers who were offered participation in the trial were matched to a sample of eligible smokers (n = 277), selected from the rosters of the 42 GPs collaborating in the trial, who had not been invited to participate. The probability of being offered enrollment, estimated through a multiple conditional logistic regression model, assuming the GP as the matching variable, was significantly increased for intermediate (10-19 cigarettes per day: odds ratio [OR] = 4.13; 95% confidence interval [CI]: 2.63-6.47) and heavy (20 cigarettes per day or more: OR = 10.12; 95% CI: 6.51-15.75) smokers, for smokers diagnosed with chronic cardiovascular (OR = 2.06; 95% CI: 1.19-3.58), or respiratory (OR = 2.50; 95% CI: 1.40-4.48) diseases, and for smokers mentioning an intermediate number (2-4) of past quit attempts (OR = 3.70; 95% CI: 2.18-6.28). General Practitioners focused their recruitment activity on higer-risk smokers or smokers who had tried to quit, to offer more clues for intervention. Assessing the potential public health benefit of preventive interventions requires a more systematic evaluation of the generalizability of the reported findings. PMID- 9973078 TI - On misclassification of smoking. PMID- 9973079 TI - The radiation biology of boron neutron capture therapy. AB - Boron neutron capture therapy (BNCT) is a targeted radiation therapy that significantly increases the therapeutic ratio relative to conventional radiotherapeutic modalities. BNCT is a binary approach: A boron-10 (10B)-labeled compound is administered that delivers high concentrations of 10B to the target tumor relative to surrounding normal tissues. This is followed by irradiation with thermal neutrons or epithermal neutrons which become thermalized at depth in tissues. The short range (5-9 microm) of the alpha and 7Li particles released from the 10B(n,alpha)7Li neutron capture reaction make the microdistribution of 10B of critical importance in therapy. The radiation field in tissues during BNCT consists of a mixture of components with differing LET characteristics. Studies have been carried out in both normal and neoplastic tissues to characterize the relative biological effectiveness of each radiation component. The distribution patterns and radiobiological characteristics of the two 10B delivery agents in current clinical use, the amino acid p-boronophenylalanine (BPA) and the sulfhydryl borane (BSH), have been evaluated in a range of normal tissues and tumor types. Considered overall, BSH-mediated BNCT elicits proportionately less damage to normal tissue than does BNCT mediated with BPA. However, BPA exhibits superior in vivo tumor targeting and has proven much more effective in the treatment of brain tumors in rats. In terms of fractionation effects, boron neutron capture irradiation modalities are comparable with other high-LET radiation modalities such as fast-neutron therapy. There was no appreciable advantage in increasing the number of daily fractions of thermal neutrons beyond two with regard to sparing of normal tissue in the rat spinal cord model. The experimental studies described in this review constitute the radiobiological basis for the new BNCT clinical trials for glioblastoma at Brookhaven National Laboratory, at the Massachusetts Institute of Technology, and at the High Flux Reactor, Petten, The Netherlands. The radiobiology of experimental and clinical BNCT is discussed in detail. PMID- 9973080 TI - Measurement of distributions of small-scale energy depositions from low-linear energy transfer particles using the superheated drop detector. AB - We have developed a new detection method for measuring distributions of energy depositions from particles characterized by low linear energy transfers (LETs). In particular, we have developed a detection system to measure energy depositions produced by electrons and photons on nanometer scales. The detector is based upon the operational principles of the superheated drop detector (SDD). SDDs consist of tiny droplets of superheated liquid suspended within a gel-like emulsion. The SDDs in this study are fabricated using Freon-115 and a glycerol-based gel as the superheated liquid and host medium. This SDD configuration is operated as a threshold temperature-dependent detector for measuring nanoscopic distributions of energy depositions from low-LET particles. Measured results are compared to the calculated distributions of energy depositions along an electron track. A new electron track code, ESLOW3.1, is used to perform the computational study. Measurements show good agreement with computational results in the energy deposition range of 40-200 eV. PMID- 9973081 TI - The use of microdosimetric moments in evaluating cell survival for therapeutic alpha-particle emitters. AB - In evaluating the efficacy of alpha-particle emitters, a cell survival curve is often determined for a particular source-target configuration. Investigators often wish to use this information about survival for a different source-target configuration which might be more appropriate for a therapeutic application. Since the population cell survival parameter, D0, is a function of the source target configuration, it is important to determine the individual cell survival parameter, z0, which is more fundamental. Unlike D0, z0 does not depend upon the microdosimetric variations in the specific energy distribution resulting from changes in the source-target configuration. Instead it is determined by the cell sensitivity and the radiation quality. However, the calculation of z0 from the data on survival involves computing the microdosimetric specific energy distributions of the radiation. This paper describes an approximate but sufficiently accurate method for determining z0 from D0 if the first and second moments of the single-hit specific energy distributions are known or can be estimated. Examples of applications are given. This may alleviate the need for multihit microdosimetric calculations. PMID- 9973083 TI - Hydroxyl radical-induced hydrogen/deuterium exchange in amino acid carbon hydrogen bonds. AB - Hydroxyl radicals produced by radiolysis under anaerobic conditions in the presence of dithiothreitol and D2O have been shown to be capable of inducing hydrogen/deuterium (1H/2H) exchange in carbon-hydrogen bonds of amino acids. When the solution is saturated with N2O, a 1H/2H exchange efficiency of 38% (based on the G value of 5.6 x 10(-7) mol J(-1) for hydroxyl radical) was determined by measuring the amino acid isotope ratio [M+H+1]+/[M+H]+ using electrospray ionization-mass spectrometry. The incorporation of 2H was proportional to the amount of hydroxyl radical generated and required the presence of dithiothreitol. Using standard anaerobic reaction conditions with dithiothreitol and N2O, incorporations of 2H of 3% and 8% into L-valine (100 microM, 35 microM DTT) and L leucine (100 microM, 31 microM DTT), respectively, were achieved after a dose of 89 Gy and, using d8-DL-valine (100 microM, 35 microM DTT) with H2O as the solvent, approximately 2% incorporation of protium was detected. Additionally, 1H/2H exchange into the peptide (Ala2)-leucine enkephalin produced 6% incorporation of 2H. These results directly demonstrate the ability of sulfhydryl groups to mediate the chemical repair of proteins through hydrogen-atom donation to an amino acid carbon-centered radical, thus providing a means of isotopically labeling solvent-accessible amino acid residues of peptides and proteins. PMID- 9973082 TI - The effect of packing and conformation on free radical yields in films of variably hydrated DNA. AB - This work investigates the direct-type action of radiation (involving electron addition and electron abstraction) on DNA. Specifically, the effects of DNA hydration, conformation and packing on free radical yields are examined. The fact that these variables are interdependent complicates the analysis of how each variable affects free radical yields. The hydration dependence of free radical yields in films of both Li and Na DNA was examined. At low levels of DNA hydration (less than 25 waters per nucleotide), the relatively high free radical yields and the lack of water-derived radicals are evidence that damage transfer from the DNA solvation shell to the DNA molecule occurs. The scatter of measured free radical yields is significant (50-70%) in Li DNA, while in Na DNA it is much less (<25%). Our conclusions hinge upon two known differences between Li DNA and Na DNA: (1) At low DNA hydrations, the conformation of Na DNA undergoes several changes with increasing hydration, while the conformation of Li DNA is relatively constant over the same range. (2) Compared to Na DNA, Li DNA is more prone to self-associate, giving rise to macroscopic and microscopic crystalline domains in Li DNA films. The greater scatter of free radical yields in Li DNA films is therefore attributed to variability in packing. By virtue of the greater reproducibility of free radical yields in Na DNA films, the effects of DNA packing, conformation and hydration can be ascertained. In Na DNA, hydration dependent changes in free radical yields are attributed primarily to changes in DNA packing. PMID- 9973084 TI - A rapid preparation of extracts for DNA replication in vitro. AB - A rapid preparation of cytoplasmic extracts using a small number of cells was developed for SV40 DNA replication in vitro. Compared with methods published previously, this new method has two advantages: First, cells of several human cell lines can be processed at the same time. Second, the time of preparation has been reduced from 10 h to 2 h by adding sucrose and reducing the concentration of NaCl in the dialysis buffer. Activities of extracts prepared from small numbers of cells with this new method to support SV40 DNA replication in vitro are high, reproducible and comparable to that of extracts from large numbers of cells with the methods traditionally used. These advantages will make it possible to study the regulation of DNA replication in irradiated or drug-treated human cells more efficiently. Therefore, this simple method should be a useful complement to the large-scale preparation for the general study of regulation of DNA replication in human cells. PMID- 9973085 TI - Radiation-induced apoptosis and limb teratogenesis in embryonic mice. AB - In utero irradiation of the fetus during the period of organogenesis induces a dramatic increase in malformation. However, the mechanisms underlying the teratogenesis remain to be elucidated. In the present study, the correlation between radiation-induced apoptosis and limb malformation was examined in mice. The mice were exposed to X rays in utero on day 11 of gestation during the period of organogenesis of limb buds. A marked increase in the number of apoptotic cells in the predigital regions in the forelimb buds was detected 4 h after irradiation. The preinterdigital regions of the forelimb buds did not show such an increase at the same time. Aphlangy and ectrodactyly were the main types of anomalies observed on day 19 in the limbs of the fetuses irradiated with 5 Gy. The increases in prenatal death and teratogenesis in limb digits in living fetuses were dependent on dose. The possible mechanisms involved are discussed. PMID- 9973086 TI - Radioprotection of the intestinal mucosa of rats by probucol. AB - Probucol is a lipid-regulating drug that also has antioxidant properties. This study was designed to test the possibility that probucol could provide radioprotection of the intestine when administered either intralumenally or systemically. Tissue damage was evaluated histologically by quantifying the number of crypts per circumference and the mucosal height. Animals were sacrificed 5 days after 11 Gy of X irradiation. In one series of experiments, a loop of mid small bowel was exteriorized operatively and compartmentalized into segments, each filled with probucol or saline. Intralumenal administration of probucol prior to irradiation led to a significantly greater number of crypts per circumference and mucosal height compared to saline-filled irradiated controls. In another series of experiments, five groups of rats were irradiated: (1) probucol in the small bowel lumen, (2) intravenous probucol, (3) probucol by gavage, (4) probucol added to standard rat chow and (5) saline control. In the rats given probucol intravenously prior to X irradiation, crypt numbers and mucosal height were significantly enhanced. Probucol given by gavage also resulted in protection. Rats fed a diet containing probucol showed no significant protection. Topical administration was more effective than systemic. Probucol protects the intestinal mucosa from acute radiation damage when given topically, intravenously or by gavage, but does not do so when given as a dietary supplement. PMID- 9973087 TI - In vivo radioprotection by ocimum flavonoids: survival of mice. AB - Two flavonoids, orientin and vicenin, isolated from the leaves of the Indian plant Ocimum sanctum were tested for their radioprotective effect in mice. Both compounds provided protection against death from gastrointestinal syndrome as well as bone marrow syndrome when injected intraperitoneally (i.p.) before whole body exposure to 11 Gy gamma radiation. The optimum drug dose for protection was 50 microg/kg body weight: An increase in the drug dose did not increase protection. No acute toxicity was observed at doses as high as 100 mg/kg body weight of either compound. Maximum protection was obtained when either compound was injected i.p. 30 min before irradiation. Changing the route of administration or the interval between drug injection (i.p.) and irradiation reduced protection. Drug treatment after irradiation was not very effective. Vicenin was slightly better than orientin in increasing survival at 30 days; protection by vicenin also lasted longer. Dose modification factors (DMFs) for the LD50 were 1.37 for vicenin and 1.30 for orientin. Radical scavenging activity has been demonstrated for both orientin and vicenin, and this appears to be one of the mechanisms of protection by these flavonoids. PMID- 9973088 TI - Thermoradiotherapy with hydralazine: the effect of preirradiation of the tumor bed on blood flow and growth delay of Ehrlich carcinoma. AB - Ehrlich carcinoma transplanted into preirradiated calf muscle of mice was used as a model for tumor recurrence after unsuccessful radiotherapy. Due to the tumor bed effect (TBE), these grafts grew more slowly than control tumors implanted in the unirradiated tissue. When these tumors achieved the same volume (0.3-0.4 cm3), in 10-11 days for tumors implanted in irradiated tissue and 7-8 days for control tumors, they were treated with radiation, the tumor blood flow inhibitor hydralazine, and hyperthermia, alone or in different combinations. In the case of the trimodality treatment, single irradiation of tumors at a dose of 12.5 Gy was followed 2.5-3 h later by administration of hydralazine (2.5 mg/kg) and local hyperthermia (water bath, 43 degrees C for 30 min). The growth delay induced in the different tumor types by irradiation, hydralazine and hyperthermia, alone or in different combinations, was related to the blood flow measured in the tumors by the 133Xe clearance technique 24-48 h after treatment. It was shown that the reduction of blood flow after treatment with hyperthermia or hydralazine was approximately equal in both types of tumors. However, the combined inhibiting effect of these agents differed in the tumors: It was synergistic in control tumors and close to additive in tumors implanted in irradiated tissue. In terms of the specific tumor growth delay, the latter tumors were slightly more sensitive to hyperthermia, but were more resistant to radiation and thermoradiotherapy compared to control tumors. Hydralazine potentiated the tumoricidal effects of heat alone and heat combined with radiation. The enhancement was more substantial in control tumors compared to tumors implanted in irradiated tissue. A general correlation between the hydralazine-induced enhancement of the effects of heat on tumor blood flow and growth delay was observed. In tumors implanted in irradiated tissue, the inhibition of perfusion after treatment with hydralazine plus hyperthermia was smaller, and presumably a less marked treatment response to these agents (with or without radiation) was therefore achieved as a result in these tumors compared to the control tumors. PMID- 9973089 TI - Theoretical and experimental tests of a chromosomal fingerprint for densely ionizing radiation based on F ratios calculated from stable and unstable chromosome aberrations. AB - In the present study, F ratios for both stable chromosome aberrations, i.e. ratios of translocations to pericentric inversions, and unstable aberrations, i.e. dicentrics and centric rings, were measured using fluorescence in situ hybridization. F ratios for stable aberrations measured after exposure to low (2.89 Gy 60Co gamma rays) and high-LET (0.25 Gy 56Fe ions; 1.25 Gy 56Fe ions; 3.0 Gy 12C ions) radiation were 6.5 +/- 1.5, 4.7 +/- 1.6, 9.3 +/- 2.5 and 10.4 +/- 3.0, respectively. F ratios for unstable aberrations measured after low (2.89 Gy 60Co gamma rays) and high-LET (0.25 Gy 56Fe ions; 3.0 Gy 12C ions) radiations were 6.5 +/- 1.6, 6.3 +/- 2.3 and 11.1 +/- 3.7, respectively. No significant difference between the F ratios for low- and high-LET radiation was found. Further tests on the models for calculation of the F ratio proposed by Brenner and Sachs (Radiat. Res. 140, 134-142, 1994) showed that the F ratio may not be straightforward as a practical fingerprint for densely ionizing radiation. PMID- 9973090 TI - Proceedings of the American Statistical Association Conference on Radiation and Health. San Diego, California, USA. June 14-17, 1998. PMID- 9973091 TI - Comments on the hazard function of a two-stage carcinogenesis model. PMID- 9973092 TI - Comments on the paper "Adaptive response in embryogenesis" by Wang et al., Radiat. Res. 150, 120-122 (1998) PMID- 9973093 TI - Screening decreases prostate cancer death: first analysis of the 1988 Quebec prospective randomized controlled trial. AB - BACKGROUND: The 46,193 men aged 45 to 80 years registered in the electoral roll of Quebec City and its Metropolitan area were randomized in November 1988 between screening and no screening in a study aimed of assessing the impact of prostate cancer screening on cause-specific death. METHODS: At first visit, screening included measurement of serum prostatic specific antigen (PSA) using 3.0 ng/ml as upper limit of normal and a digital rectal examination (DRE). Transrectal echography of the prostate (TRUS) was performed only if PSA and/or DRE was abnormal and biopsy was then done, only if PSA was above the predicted PSA value. At follow-up visits, PSA alone was used as prescreening. RESULTS: 137 deaths due to prostate cancer occurred between 1989 and 1996, inclusively, in the 38,056 unscreened men while only 5 deaths were observed among the 8,137 screened individuals. The prostate cancer death rates during the eight-year period were 48.7 and 15 per 100,000 man-years in the unscreened and screened groups, respectively, for a 3.25 odds ratio in favor of screening and early treatment (P < 0.01). CONCLUSIONS: If PSA screening is started at the age of 50 years (or 45 years in the higher risk population), annual or biannual PSA alone is highly efficient to identify the men who are at high risk of having prostate cancer. Coupled with treatment of localized disease, this approach demonstrates, for the first time, that early diagnosis and treatment permits a dramatic decrease in deaths from prostate cancer. PMID- 9973094 TI - Numerical chromosomal anomalies in latent adenocarcinomas of the prostate. AB - BACKGROUND: Even the high incidence of clinically diagnosed prostate cancer is exceeded by the frequency of tumors detected at autopsy. However, there is some debate concerning the malignant potential of these so-called "latent prostate cancers." In this study, prostate cancers detected at autopsy were investigated for the presence of numerical aberrations of chromosomes 7, 10, 17, X, and Y. METHODS: Prostates from 57 autopsies, performed on male patients aged 45 years or older, were histologically investigated for the presence of cancer. Interphase cytogenetics, an in situ hybridization method with chromosome-specific probes, was performed on paraffin sections. RESULTS: Of the 57 specimens investigated, 23 contained foci of prostate cancer. Three prostates contained more than one tumor focus. Interphase cytogenetics could be performed successfully in 19 specimens. Of the 22 tumor foci investigated, 14 were disomic and 8 were nondisomic for the five chromosomes tested. Ploidy correlated significantly with the presence of a Gleason score of 7 or higher (P = 0.0109), but not with a tumor volume larger than 0.5 cm3, or with patient age over 75 years. CONCLUSIONS: Some latent prostate cancers display a nondisomic chromosomal status and a low histologic differentiation in spite of a small tumor volume, suggesting a more aggressive potential in a subset of these tumors. PMID- 9973095 TI - Quality-adjusted survival (Q-TWiST) analysis of EORTC trial 30853: comparing goserelin acetate and flutamide with bilateral orchiectomy in patients with metastatic prostate cancer. European Organization for Research and Treatment of Cancer. AB - BACKGROUND: The first data analysis of the European Organization for Research and Treatment of Cancer (EORTC) 30853 trial indicated a significantly longer time to progression and duration of survival for the maximal androgen blockade (MAB) treatment arm. However, the MAB treatment arm had a higher frequency of reported side effects. METHODS: The quality-adjusted survival (Q-TWiST) method was applied to perform a secondary analysis of the EORTC 30853 trial in order to obtain a quality-adjusted survival (QAS) analysis. Two models with different definitions of the progression health state were used for the analysis. In the first model, progression was defined by both objective and subjective criteria, and in the second model only by increase in pain score. The approach was also extended to include an analysis using actual utility scores (Q-tility) of patients in the relevant health states. RESULTS: Based on Q-tility scores obtained from a separate study of a cohort of prostate cancer patients, the QAS analysis resulted in a 5.2-month difference (95% CI, -1.1; 11.5 months) in favor of zoladex and flutamide, equal in magnitude to the benefit found in the unadjusted survival analysis. CONCLUSIONS: A QAS analysis such as the Q-TWiST method may be preferred over the unadjusted approach in clinical trials where the health states are clearly distinct, and differ significantly in either duration or quality of life (QOL), or both. The second model, with progression defined as increase in pain score, made no difference to the results in this study because of the small difference in duration of the pain-progression health state between treatment arms. However, Q-tility scores from the separate cross-sectional study that was used in this Q-TWiST analysis showed that a subjective definition of health states better reflects differences in QOL between the health states that the patients experience during follow-up. PMID- 9973096 TI - Differential growth rates in stromal cultures of human prostate derived from patients of varying ages. AB - BACKGROUND: This study was undertaken to attempt to characterize changes in in vitro growth rates and cellular phenotypes of human prostatic stroma associated with aging and/or development of benign prostatic hyperplasia (BPH). METHODS: Prostate stromal cell strains were established from 12 tissue donors of varying age. Culture growth rate was determined by cell counts over a 6-day period. Cell phenotype was assessed by immunocytochemical staining for smooth muscle alpha actin, smooth muscle myosin, and prolyl-4-hydroxylase. RESULTS: Growth rates of prostate stromal strains in vitro varied. Stromal cells derived from aged males with BPH had significantly slower growth rates than cells from younger donors. A positive reaction for prolyl-4-hydroxylase, a mesenchymal cell marker, was present in all cell cultures regardless of donor age. Expression of smooth muscle specific actin, a nonspecific smooth muscle cell marker, was present in 48-79% of prostate stromal cultures. Staining for smooth muscle myosin, a specific smooth muscle cell marker, was found to vary significantly with age. The percentage of smooth muscle myosin-positive cells derived from males aged 15, 45, 57, and 72 years were 0.70 +/- 0.14%, 2.12 +/- 0.30%, 4.20 +/- 0.89%, and 26.25 +/- 1.0%, respectively. The shape and size of actin- and/or myosin-positive stromal cells from a 72-year-old donor culture were also usually larger and polygonal in shape as compared to thin and elongated shapes in 15-year-old donor cultures. The shape of actin- and/or myosin-positive cells from a 45-year-old donor culture demonstrated both phenotypes. CONCLUSIONS: These results suggest that in human prostate stromal cells cultured as described, the growth rate decreases, the percent of smooth muscle cells increases, and the cellular shape changes with increasing donor age and/or development of BPH. PMID- 9973097 TI - Prostate secretory protein (PSP94) suppresses the growth of androgen-independent prostate cancer cell line (PC3) and xenografts by inducing apoptosis. AB - BACKGROUND: PSP94 (prostate secretory protein of 94 aa; also called PIP), one of the predominant proteins secreted into the seminal fluid, was proposed as an independent diagnostic/prognostic marker for prostate cancers. It was also shown to inhibit rat prostate cancer growth. In this study, we investigated the effect of purified PSP94 on the growth of androgen-independent human prostate cancer cells (PC3) and its potential mechanism of action. METHODS AND RESULTS: PSP94, in a dose- and time-dependent manner, inhibited the growth of PC3 cells. The protein demonstrated a stronger inhibitory effect on the colony-forming ability of PC3 cells in soft agar. A daily injection of PSP94 at 5 microg/kg/body weight resulted in a 50-60% inhibition in the growth of PC3 xenografts in athymic mice. PC3 cell growth inhibition by PSP94 resulted from cell death characteristic of morphological apoptosis, which was confirmed by dual fluorescence microscopy, electron microscopy, and DNA fragmentation assays. Mechanistic studies indicated that PSP94 enhanced the expression of proapoptotic protein Bax without affecting Bcl-2 levels. CONCLUSIONS: This study suggests that PSP94 may represent a novel, apoptosis-based, antitumor agent applicable to the treatment of hormone refractory human prostate cancers. PMID- 9973098 TI - Involvement of heparin affin regulatory peptide in human prostate cancer. AB - BACKGROUND: Heparin affin regulatory peptide (HARP) composes, together with midkine (MK), a new family of heparin-binding growth/differentiation factors. Recently, HARP was incriminated in cancer progression, as an angiogenic factor and as a tumor growth factor. In this study, we analyzed the possible involvement of HARP in human prostate cancer (Pca). METHODS: The localization of HARP protein and its mRNAs in normal prostate (n = 5), benign prostate hyperplasia (BPH) (n = 7), and prostate cancer (Pca) (n = 9) was analyzed by immunohistochemistry and in situ hybridization. The mitogenic activity of this growth factor for prostate epithelial cells was determined with a thymidine incorporation assay. HARP cDNA was transfected into normal prostate epithelial (PNT-1A) cells, and their growth was evaluated by soft-agar growth assay. RESULTS: We found HARP protein associated with epithelial cells in PCa but not in normal prostate or BPH, while the corresponding mRNAs were located in the stromal compartment. Furthermore, HARP is mitogenic for PNT-1A, LNCaP, and DU-145 cells. Overexpression of the human HARP in PNT-1A transfected cells induced both anchorage-independent growth and growth at low serum concentrations. CONCLUSIONS: Our results suggest that HARP may act in a paracrine manner from mesenchymal to tumoral epithelial cells, and may play a role in the molecular mechanisms that regulate prostate tumor cell growth. PMID- 9973099 TI - Determination of optimal freezing parameters of human prostate cancer in a nude mouse model. AB - BACKGROUND: We sought to determine whether more than one freeze/thaw cycle is required and what minimum temperature reliably kills prostate cancer in vivo. METHODS: Two human prostate cancer cell lines (LNCaP and PC3) were implanted subcutaneously in male nude BALB/c mice. Tumors were frozen with contemporary cryosurgery equipment and monitored for temperature, size, and serum prostate specific antigen (PSA) measurements. The tumors were subjected to one or two freeze/thaw cycles through a wide range of temperatures from 0 - -80 degrees C. RESULTS: These experiments show that a single freeze/thaw to a temperature < -40 degrees C is adequate to kill most tumor cells in this mouse model of prostate cancer. CONCLUSIONS: Freezing prostate cancer to < -40 degrees C and ensuring that the entire tumor is frozen is more important than additional freeze/thaw cycles in this experimental model. PMID- 9973100 TI - Differences in prostate size between patients from University and Veterans Affairs Medical Center populations. AB - BACKGROUND: Numerous studies on prostatic disease have been performed at Veterans Affairs (VA) Medical Centers. Recent investigations evaluating early detection of prostate cancer provide insight that the average prostate volume may be different between patients with similar clinical findings who are from different hospital settings. The objective of this study was to compare prostate size between men from University and VA Medical Centers. METHODS: Patients were enrolled retrospectively from 1989-1996 from the Urology Clinics at a University and a VA Medical Center. All men underwent transrectal ultrasound-guided sextant biopsy of the prostate owing to either an elevated prostate-specific antigen (PSA) level and/or abnormal digital rectal examination (DRE) detected prior to biopsy. Prostate volume was calculated using the ellipsoid three-diameter formula based on transrectal ultrasound measurements. RESULTS: There were 1,311 men included in the analysis: 717 were from the VA, and 594 were from the University. The average prostate volume was significantly smaller among VA patients both for men with cancer (P = 0.0004) and for men with no evidence of malignancy (P < 0.0001). Overall, the average prostate volume was 38.5 cm3 (median, 32.5 cm3) among men from the VA compared to 46.8 cm3 (median, 39.3 cm3) among men from the University Medical Center. Men from the VA were older (mean +/- SD = 68 +/- 7.3) than men from the University (mean +/- SD = 66 +/- 7.7) (P = 0.004) and there was no significant difference in PSA levels between the two groups of patients (P = 0.11). Intriguingly, the incidence of cancer was significantly lower at the VA (24.5%) compared to the University (35.9%) (P < 0.0001). CONCLUSIONS: The variance in prostate size suggests that there are significant differences between the two patient populations. Proposed factors leading to this discrepancy include differences in socioeconomic factors, environmental factors, and changes in hormonal milieu related to alcohol and tobacco use. These results may have significant implications regarding the interpretation and extrapolation of results from previous studies performed at a single hospital setting. PMID- 9973101 TI - Targeted cytotoxic analog of luteinizing hormone-releasing hormone AN-207 inhibits the growth of PC-82 human prostate cancer in nude mice. AB - BACKGROUND: Receptors for luteinizing hormone-releasing hormone (LH-RH) found in prostate cancers might be used for targeting of chemotherapeutic agents. Doxorubicin derivative 2-pyrrolinodoxorubicin (AN-201) can be linked to carrier analog [D-Lys6]LH-RH to form the targeted cytotoxic analog of LH-RH, AN-207. METHODS: We evaluated the effects of AN-207 and its components on the growth of LH-RH receptor-positive human prostate cancer PC-82 xenografted into nude mice. Analog AN-207, radical AN-201, carrier [D-Lys6]LH-RH, or a mixture of [D-Lys6]LH RH and AN-201 were injected intravenously once at doses of 200 nmol/kg. Tumor growth, body weight, total WBC counts, and serum prostate-specific antigen (PSA) were determined. Receptors for LH-RH on PC-82 tumors were evaluated, and the expression of mRNA for LH-RH receptors was assessed by RT-PCR. RESULTS: Eight weeks after administration of cytotoxic analog AN-207, there was a 67.8% reduction in tumor volume (P < 0.01), 70.7% decrease in tumor burden (P < 0.01), and 36.5% decrease in serum PSA levels (P < 0.01) as compared with controls. Only one of 8 animals treated with AN-207 died. Cytotoxic radical AN-201 caused a 34.2% (not significant, NS) reduction in tumor volume with no change in serum PSA, and killed 3 of 8 mice due to toxicity. Carrier [D-Lys6]LH-RH and the unconjugated mixture of [D-Lys6]LH-RH and AN-201 had no effect on tumor growth. LH-RH receptors as well as the expression of their mRNA were found in PC-82 tumors. PMID- 9973103 TI - Defeating prostate cancer: crucial directions for research--excerpt from the report of the Prostate Cancer Progress Review Group. PMID- 9973102 TI - Effects of pituitary hormones on the prostate. AB - BACKGROUND: Although essential, androgens alone are not sufficient to induce normal growth and functionality of the prostate. Nonandrogenic hormones must also be involved in the proliferation of the prostate cancer cells which do not respond to antiandrogenic therapy and which thus become androgen-independent. Prolactin, but also growth hormone and luteinizing hormone, are potentially able to act on both normal and abnormal prostatic cells. METHODS: In this review we summarize data from the literature concerning the physiological and pathological implications of prolactin, growth hormone, and luteinizing hormone on the prostate. RESULTS: In rodent prostates, prolactin and growth hormone can induce a variety of effects independently of androgens (e.g., transactivation of certain genes, or synthesis of the major secretion products). Moreover, hyperprolactinemia is responsible for inflammation and dysplasia of the gland, while growth hormone promotes the development of prostate tumors in vivo in the mouse and rat. Growth hormone acts on the gland directly, through prostatic growth hormone receptors, and/or indirectly via the stimulation of insulin-like growth factor-I (IGF-I) synthesis in the liver. Luteinizing hormone receptor is expressed in rat and human prostates. Luteinizing hormone increases the amount of various transcripts in the rat prostate through an androgen-independent pathway. CONCLUSIONS: Prolactin, growth hormone, and luteinizing hormone, alone or synergistically with androgens, play physiologically significant roles in the normal prostate. The involvement of these hormones in the development of benign prostatic hyperplasia and prostatic carcinoma is an issue that needs to be addressed. PMID- 9973104 TI - Comparative study of glycoconjugates of the rat prostatic lobes by lectin histochemistry. AB - BACKGROUND: The rat prostate gland is composed of several distinct lobes: the ventral, lateral, dorsal, and anterior (also called the coagulating gland). Each prostatic lobe is different in its morphology, secretions, and response to hormones. METHODS: The present study characterized and compared the expression of glycoconjugates in three different lobes (ventral, lateral, and dorsal) of the Noble rat prostate gland by lectin histochemistry, using a battery of 30 different lectins. RESULTS: The results indicate that different prostatic lobes elaborate and secrete different glycoconjugates. The dorsal prostatic epithelium secretes mainly in an apocrine mode, as characterized by the presence of apical cytoplasmic blebs which are absent in the other two lobes, though merocrine secretion is also suggested. These cytoplasmic blebs were rich in Man, GlcNAc, Gal/GalNac, Fuc, NeuAc(alpha2,6)Gal, and oligosaccharides. Two types of cytoplasmic belbs were also identified according to their lectin bindings: blebs stained by S-Con A, LCA, PWA, UEA-II, RCA-I, DBA, ECA, WFA, Jacalin, MPA, SJA, LTA, UEA-I, PHA-E, and PHA-L, and some blebs stained by S-WGA, SBA, HAA, HPA, VAA, BPA, MAA, and SNA. The lectins, which reacted with the second type of blebs, also revealed some cytoplasmic granules in the dorsal prostatic epithelial cells. The epithelium of the lateral prostate showed weak or negative reactions to lectins, suggesting that it may express fewer glycoconjugates as compared to the other two lobes. The epithelial Golgi region of the ventral prostate is the most developed among the three lobes, and contained abundant GlcNAc, alpha/beta GalNAc, and NeuAc(alpha2,6)Gal residues, as shown by its intense reactions to S WGA, DBA, SBA, HAA, HPA, WFA, and SNA. GS-I-B4 reacted specifically with the basal epithelial cells in all three lobes, indicating that glycoconjugates with terminal alpha-Gal/GalNAc were commonly expressed in these basal cells. The basal cells in ventral prostate might express more complex glycoconjugates, as they were also stained by PWA, RCA-I, ECA, and PHA-L, in addition to GS-I-B4, suggesting that these basal cells contained more Gal(beta1,4)GlcNAc and Gal(beta1,4)GlcNAc(alpha1,2)Man residues. GS-I-B4 and PHA-L also demonstrated a differential staining of the stromal smooth muscles and their associated extracellular matrix in the three prostatic lobes, suggesting that these structural components in different prostatic lobes were different in their complex oligosaccharide contents, which probably has an influence on the epithelial-stromal interaction in the prostate. CONCLUSIONS: In summary, the present study has established for the first time the expression patterns of glycoconjugates in the three lobes of the Noble rat prostate gland and suggests that certain lectins are useful as histochemical markers for the three individual prostatic lobes. PMID- 9973105 TI - Effects of mepartricin, a polyene macrolide agent, on fecal excretion and serum concentration of estrogen and number of prostatic estrogen receptors in immature rats. AB - BACKGROUND: Mepartricin, an antifungal agent, was investigated for effects on fecal excretion and serum concentration of sex steroids and the number of sex steroid prostatic receptors in immature rats. METHODS: Mepartricin was orally administered at 2.5, 5, and 10 mg/kg once daily for 2 weeks. Fecal estrogen and testosterone excretions, serum estrogen, testosterone and luteinizing hormone concentrations, and numbers of prostatic estrogen and androgen receptors were assayed. Prostate weight was also monitored. RESULTS: Fecal estrogen excretion showed a dose-dependent increase, which was significant for the two higher dosages. Conversely, the serum estrogen concentration and prostatic estrogen receptors were significantly decreased. No significant changes in fecal testosterone excretion, serum testosterone and luteinizing hormone concentrations, and prostatic androgen receptors were observed. Prostate weight was significantly reduced at 5 mg/kg, but we did not observe dose-dependency. CONCLUSIONS: Mepartricin increases fecal excretion of estrogen by binding with it in the intestinal tract, which results in reducing the serum estrogen concentration and number of prostatic estrogen receptors. PMID- 9973106 TI - Inability of bone turnover marker as a strong prognostic indicator in prostate cancer patients with bone metastasis: comparison with the extent of disease (EOD) grade. AB - BACKGROUND: Although clinical investigations of bone turnover markers in prostate cancer patients have been conducted, the relationships of pretreatment levels of the markers to the prognosis of patients with bone metastasis has not been fully examined. METHODS: The serum levels of carboxy-terminal propeptide of type I procollagen (PICP) and carboxy-terminal telopeptide of type I collagen (ICTP), alkaline phosphatase (ALP), and prostate-specific antigen (PSA) were examined in 48 untreated prostate cancer patients with bone metastasis, and the prognoses of the patients were evaluated using univariate and multivariate analyses. RESULTS: The patients with low PICP or ALP values had significantly better outcomes in terms of cause-specific survival compared to the patients with high PICP or ALP values. There was no significant difference in survival between patients with high and low ICTP or PSA values. The multivariate analysis of PICP, ICTP, ALP, PSA, and extent of disease (EOD) grade revealed that only the EOD grade was an important prognostic indicator for survival. CONCLUSIONS: These results demonstrate that the extent of bone metastasis evaluated by bone scintigrams is a more important prognostic indicator than are the serum biochemical markers of bone turnover. PMID- 9973107 TI - Identification of dipeptidyl peptidase IV as the antigen of a monoclonal anti prostasome antibody. AB - BACKGROUND: Our purpose was to elucidate the identity of an antigen of a monoclonal antibody against prostasomes, which are prostate-derived organelles occurring freely in human semen. METHODS: Monoclonal antibodies against prostasomes were generated by intrasplenic immunization to allow better characterization of the prostasomes. One third of the resulting antibodies bound to a 110-kDa prostasomal protein on Western blots. RESULTS: The antigen was purified from seminal prostasomes by anion exchange chromatography and gel electrophoresis. After in-gel digestion and amino-acid sequence analysis of selected peptides, it was identified as dipeptidyl peptidase IV (DPP IV), EC 3.4.14.5, also known as T-cell-activating antigen CD26. No DPP IV could be detected in the supernatant obtained after preparative ultracentrifugation of the prostasomes. CONCLUSIONS: DPP IV/CD26 is structurally bound to prostasomes rather than being free in seminal fluid. This enzyme may play a critical role in the promoting effect of prostasomes on forward motility of spermatozoa. PMID- 9973108 TI - Overexpression of cyclin D1 is rare in human prostate carcinoma. AB - BACKGROUND: Overexpression of cyclin D1 has been documented in a number of human cancers. Increased expression of cyclin D1 can contribute to cellular transformation and abnormal proliferation. METHODS: Quantitative RT-PCR and/or Western blot analysis were used to determine the level of cyclin D1 expression in 96 human prostate tumors, 15 benign prostate hyperplasias, 4 prostate cancer cell lines, and 3 xenografts. RESULTS: Our results demonstrate that 4.2% of the prostate tumors examined overexpressed cyclin D1 transcripts. In the cell lines, expression was normal, with the exception that reduced levels of cyclin D1 transcript and protein were observed in the DU145 cell line, as expected from cells with mutant RB. Normal levels of cyclin D1 were found in all xenograft tumors and BPH specimens examined. CONCLUSIONS: These data show that overexpression of cyclin D1 occurs rarely in human prostate tumors. However, when overexpression of cyclin D1 does occur, it may identify a subset of tumors with a different molecular biology. PMID- 9973109 TI - Suppression of the tumorigenicity of prostatic cancer cells by gene(s) located on human chromosome 19p13.1-13.2. AB - BACKGROUND: In previous reports, we used microcell fusion-mediated chromosomal transfer to introduce normal human chromosomes into highly metastatic rat prostatic cancer cells to map the location of tumor and metastasis suppressor genes. The gene for prostate-specific antigen as well as several classes of genes, including cell adhesion molecules, previously demonstrated to be altered during prostate cancer progression, were mapped to human chromosome 19. METHODS: A normal human chromosome 19 was introduced into Dunning-R3327 AT6.1 rat and TSU prl human prostatic cancer cells by microcell-mediated chromosome transfer to test the suppressive effects of this chromosome on prostate cancer. Five independent hybrid clones from Dunning-R3327 AT6.1 rat prostatic cancer cells and four independent hybrid clones from TSU-pr1 human prostatic cancer cells were isolated, karyotyped, allelotyped, and analyzed for in vitro and in vivo growth characteristics. RESULTS: Introduction of human chromosome 19 into both the rat and human prostatic cancer cells resulted in alteration of cell morphology in vitro and suppression of tumorigenicity in vivo in athymic nude mice. Highly polymorphic SSR2 markers mapped to human chromosome 19 were used to determine the portions of human chromosome 19 retained in the hybrids. These analyses identified a region localized on human chromosome 19p13.1-13.2 that is responsible for the tumor suppression of both rat and human prostatic cancer cells. The expression of several genes previously mapped to this human chromosome 19p13.1-13.2 region (i.e., ICAM-1, Notch3, and Stau) were analyzed to evaluate if they could be candidate suppressor genes for prostate cancer cell growth in vivo, but no expression patterns consistent with those predicted for a suppressor gene were observed. CONCLUSIONS: Human chromosome 19p13.1-13.2 contains potential tumor suppressor gene(s) for prostate cancer. PMID- 9973110 TI - Impaired expression and posttranslational processing of connexin43 and downregulation of gap junctional communication in neoplastic human prostate cells. AB - BACKGROUND: Gap junctional communication (GJC) has been implicated in the control of cell proliferation. Numerous cancer cells show a decrease or loss of GJC compared to their normal counterparts. Lack of adequate information on the status of gap junctions during prostate neoplasia prompted us to examine this form of cancer, which comprises about 14% of male cancer deaths in America. METHODS: Cultured normal human prostate epithelial cells and several different human prostate tumor lines were used in this study. GJC was assayed by dye transfer, whereas Western blot and immunofluorescence methods were used to examine connexin43 (Cx43) levels and the presence of gap junctions, respectively. RESULTS: Normal human prostate cultures exhibited extensive cell-communication which was completely absent in all the examined tumor cells. This disrupted communication was associated with a decreased expression and an impaired posttranslational modification of Cx43 in these cells. Abundant immunostaining of gap junctional channels by a Cx43-antibody was observed in normal prostate cells but not in tumor cells. CONCLUSIONS: Our data provide further support for the hypothesis that loss of junctional communication is a critical step in progression to human prostate neoplasia. PMID- 9973111 TI - Prostate stroma: physiology. AB - BACKGROUND: The separate structural and functional activities of the prostatic stroma were only recently discovered and are still poorly understood. METHODS: This review summarizes recent literature on the structure, and on the angiogenic, contractile, proliferative, and secretory activities mediated by the prostatic stroma and its agents. RESULTS: The stroma undergirds the acinar epithelium through its fibromuscular substance. Neovascularization of its hypoxic cells, a process driven by cytokines, especially vascular endothelial growth factor, provides fuel for glycolytic empowerment of smooth muscle contraction, growth, and secretion. Signals from the stromal complement of cholinergic and adrenergic fibers, modulated by also-elaborated nitric oxide, provide tight regulation of uroflow. Apparently, autonomic control is independent of that of the powerful endothelin, secreted by the epithelium. Superimposed on these intrinsic elements of prostatic stromal control are the effects of steroid hormones and their effectors. CONCLUSIONS: The illumination of the stroma's role in prostatic physiology, coupled with advances in knowledge of its pharmacology, should aid in our understanding, management, and prevention of prostatic disease. PMID- 9973112 TI - Infusion of dendritic cells pulsed with HLA-A2-specific prostate-specific membrane antigen peptides: a phase II prostate cancer vaccine trial involving patients with hormone-refractory metastatic disease. AB - BACKGROUND: A phase II trial was conducted to assess the efficacy of infusions of dendritic cells (DC) and two HLA-A2-specific PSMA peptides (PSM-P1 and -P2). This report describes thirty three subjects with hormone-refractory metastatic prostate cancer without prior vaccine therapy history who were evaluated and reported as a group. METHODS: All subjects received six infusions of DC pulsed with PSM-P1 and -P2 at six week intervals. Clinical monitoring was conducted pre , during, and post- phase II study. Data collected include: complete blood count, bone and total alkaline phosphatase, prostate markers, physical examination, performance status, bone scan, ProstaScint scan, chest x-ray, as well as assays to monitor cellular immune responses. RESULTS: Six partial and two complete responders were identified in the phase II study based on NPCP criteria, plus 50% reduction of prostate-specific antigen (PSA), or resolution in previously measurable lesions on ProstaScint scan. CONCLUSIONS: Over 30% of study participants in this group showed a positive response at the conclusion of the trial. This study suggested that DC-based cancer vaccines may provide an alternative therapy for prostate cancer patients whose disease no longer responds to hormone therapy. PMID- 9973113 TI - Critical analysis of false elevations in PSA results reported with the Abbott AxSYM assay. PMID- 9973114 TI - Bringing some uniformity to diversity. PMID- 9973115 TI - Percutaneous stereotactic differential radiofrequency thermal rhizotomy for the treatment of trigeminal neuralgia. AB - PURPOSE: The purpose of this study was to evaluate the effectiveness of radiofrequency thermal rhizotomy (RTR) for trigeminal neuralgia, after failure of pharmacological management. PATIENTS AND METHODS: Two hundred fifteen patients underwent RTR from 1991 to 1996 and were prospectively evaluated. These patients were characterized by age, sex, side of the face, and division(s) involved. Patients were evaluated for pain relief, recurrence requiring or not requiring reoperation, and the type and rate of complications. They were followed-up by serial clinical evaluation and telephone interview. Patients were categorized into groups: 1) Successful result: excellent, good pain relief; and 2) Unsuccessful result: fair, poor, or no pain relief. The RTR group was compared with historical controls. Follow-up ranged from 9 to 68 months (mean, 32 months) and results were evaluated at early and long-term follow-up. RESULTS: At early follow-up (defined as immediately postoperatively to 6 months), pain relief of excellent or good quality (successful result) occurred in 198 of 215 patients (92%). Fair or poor or no pain relief (unsuccessful result) occurred in 17 (8%) patients. At long-term follow-up (>6 months to 68 months), recurrence of pain that required reoperation occurred in 24 patients (11%) and recurrence of pain that did not require reoperation (medically managed) occurred in 34 patients (16%). Dysesthesia developed in 18 patients (8%); seven patients (3%) had dysesthesia alone (medically managed) and 11 patients (5%) had dysesthesia with recurrence of pain (medically or surgically managed). "Anesthesia/analgesia dolorosa" developed in four patients (1.8%) and was medically managed. At long term follow-up, 83% of patients had good to excellent pain relief (successful result). There were no mortalities, no significant morbidity, and a low rate of minor complications. CONCLUSION: With the use of this specific diagnostic approach and management algorithm, patients with trigeminal neuralgia can be successfully managed. PMID- 9973116 TI - Lag-screw fixation of anterior mandibular fractures using biodegradable polylactide screws: a preliminary report. AB - PURPOSE: The purpose of this study was to evaluate the utility of biodegradable, self-reinforced poly-L-lactide screws (SR-PLLA) for lag-screw fixation of anterior mandibular fractures. PATIENTS AND METHODS: SR-PLLA lag-screws were used to stabilize anterior mandibular fractures in 11 patients. Maxillomandibular fixation was used to treat concomitant mandibular condyle fractures for 2 weeks in four patients and for 1 and 5 weeks in two patients. Clinical and radiologic follow-up lasted for 6 months in 36% of patients and for 1 year in 64%. RESULTS: Healing of all anterior fractures was uneventful, with no displacement or delay of bony union. No adverse reactions to the biodegradable screws were seen during follow-up. CONCLUSION: Biodegradable SR-PLLA screw fixation seems to be a new and promising way of treating anterior mandibular fractures. PMID- 9973117 TI - Maxillofacial injuries associated with all-terrain vehicles. AB - PURPOSE: The purpose of this article is to report the pattern and frequency of maxillofacial injuries resulting from all-terrain vehicle (ATV) accidents, to evaluate the mechanisms of injury, to document the length of hospital stay, and to characterize other associated injuries in patients presenting to a level 1 trauma center. PATIENTS AND METHODS: The records of patients admitted to the University of Kentucky Medical Center from July 1, 1995 through August 1996 with an ATV-related injury were reviewed. Patients were included in the study if the events of their injury, demographic data, and the specifics of their perioperative care were sufficiently documented to provide the information pertinent to the investigation. Age, sex, mechanism of injury, facial injuries, associated injuries, and length of stay were the factors considered for the study. RESULTS: Seventy-two patients met the criteria for the study. Fifty-nine (82%) were male, and 13 (18%) were female. Forty patients required operative intervention. Twenty-five (35%) had soft tissue or bony injuries to the maxillofacial region. One mandibular and 13 midface fractures were identified. Twelve of the patients with midface injuries had multiple facial fractures. Orbital floor fractures occurred in seven patients. Two patients required unilateral enucleation of the globe. Ten soft tissue injuries were diagnosed. Extremity fractures (n = 16) and closed head injuries (n = 17) were the most commonly associated injuries. The length of hospital stay for all the subjects identified in the study averaged 4.7 days. ATV rollover and being thrown from a moving ATV were the most common mechanisms of injury. CONCLUSIONS: Head and maxillofacial injuries, particularly midface injuries, are common findings after ATV accidents. Orbital trauma with serious globe injury was a striking feature of this study. Multiple systems injuries should always be anticipated and identified. The public should be alerted to the hazards of imprudent recreational vehicle use. PMID- 9973118 TI - Lingual cyst with respiratory epithelium: an entity of debatable histogenesis. AB - PURPOSE: The purpose of this report was to describe a new case of lingual cyst with respiratory epithelium, to review and analyze the literature regarding lingual cyst of foregut origin and lingual alimentary cyst, and to discuss the suitable terminology for these uncommon cysts. MATERIAL AND METHODS: Data from articles published in the English language between the years 1942 and 1947 were used. RESULTS: The review of the literature showed 53 lingual cysts of which 29 could be grouped into lingual alimentary tract cysts and 24 into lingual cysts of foregut origin. There was an overlap in histologic and clinical features and embryogenesis of both cysts. CONCLUSIONS: Differentiation between both cysts cannot be supported, and until further information is accumulated it is suggested that histologic descriptive terms be used such as lingual cyst with respiratory epithelium, lingual cyst with gastric epithelium, or lingual cyst with respiratory and gastric epithelium. PMID- 9973119 TI - Complications of internal fixation of maxillofacial fractures with microplates. AB - PURPOSE: The aim of this retrospective study was to evaluate the complications of open reduction and internal fixation of maxillofacial fractures with microplates. PATIENTS AND METHODS: In 44 patients with maxillofacial trauma, fractures of the maxillofacial skeleton were treated by open reduction and internal fixation using a 1.0-mm and 1.5-mm microsystem. Simultaneously occurring fractures of the mandible or frontozygomatic suture were treated with a 2.0-mm miniplate system. Perioperative and postoperative complications were traced using patient charts, operation reports, and radiographs. The average follow-up was 46.8 months (range, 31 to 54 months). RESULTS: A total of 124 1.0-mm microplates and 546 1.0-mm microscrews, and 17 1.5-mm microplates and 75 1.5-mm microscrews, was used. The perioperative complication rate was 1.2% for the 1.0-mm screws (use of four emergency screws, breakage of one screw in the dense frontozygomatic suture area, and an insertion of a screw in a premolar root). The postoperative complication rate was 0.8% for the 1.0-mm screws (screw dislocation without clinical implication). No complications were observed with the 1.5-mm system. Plate related infection did not occur. All fractures healed well. Three patients asked for plate removal because of a vague, persisting pain in the treated area. After removal, only one patient was free of pain. A loose 1.5-mm screw was found in this patient. CONCLUSION: The overall complication rate for microsystems was 2.0%. Both microsystems proved to be a reliable modality to fix fractures of the maxillofacial skeleton. Complications can be considered incidental and of neglectable clinical significance. PMID- 9973120 TI - Telemedicine consultations in oral and maxillofacial surgery. AB - PURPOSE: The purpose of this study was to evaluate the efficiency of telemedicine consultation for preoperative assessment of patients. PATIENTS AND METHODS: A retrospective study of 43 patients was done to evaluate the efficiency of telemedicine consultation in adequately assessing patients for dentoalveolar surgery with general anesthesia and nasotracheal intubation. Efficiency was defined as the ability to conduct surgery with general anesthesia at the immediately following clinic appointment without the need for further preoperative testing, evaluation, or consultation. Thirty-five of these patients were subsequently treated. RESULTS: Ninety-five percent (33) of patients were able to undergo surgery with general anesthesia at the immediate appointment, and 100% of patients were assessed correctly, using telemedicine consultation. Two of the patients were assessed as American Society of Anesthesiologists Class III during telemedicine consultation and required further evaluation before surgery could be scheduled. No surgical procedure was canceled, and there were no anesthetic complications attributable to inadequate preoperative assessment of patients during telemedicine consultation. CONCLUSIONS: This study confirms that telemedicine consultations are as reliable as those conducted by traditional methods. Because of the reorganization of health care and the ways it is financed, it may be more economical to move data from place to place than to move doctors from place to place. Telecommunication is an efficient and cost-effective mechanism to provide preoperative evaluation in situations in which patient transport is difficult or costly. PMID- 9973121 TI - Short-term effect of the use of a frozen-stored disc allograft for repair of the osteoarthritic sheep temporomandibular joint: a preliminary report. AB - PURPOSE: The purpose of this experimental study was to evaluate the initial effect of a frozen-stored disc allograft on the osteoarthritic sheep temporomandibular joint (TMJ). MATERIALS AND METHODS: Bilateral osteoarthritis was induced in the TMJ of four sheep. Three months later, unilateral discectomy and frozen-stored disc allograft replacement were performed. The donor disc had been obtained from a healthy animal at killing. The disc was stored in a deep freezer at -70 degrees C for 1 month and thawed just before grafting. The contralateral joints were undisturbed and served as a control at 3 months. At 6 months after the initial procedure, 3 months after the repair, the four sheep were killed. RESULTS: All four grafted discs were perforated and displaced. In the repaired joints, the condylar articular surface was partly denuded in some areas, and part of the surface showed fibrous repair. The control joints showed osteoarthritic changes. CONCLUSION: Frozen-stored disc allograft is not a satisfactory interpositional material in the osteoarthritic sheep TMJ. PMID- 9973122 TI - The vascular relationship between the temporomandibular joint and the middle ear in the human fetus. AB - PURPOSE: The aim of this work was to clarify the vascular relationships between the middle ear and the temporomandibular joint region during human fetal development. MATERIALS AND METHODS: Light microscopic studies were done on 40 human fetuses from 72 mm crown-rump length (C-R) to 150 mm C-R, which were stained by various methods. Five human fetuses were dissected. Natural latex with industrial coloring was injected through the external carotid artery. All specimens were dissected bilaterally. RESULTS: The limits of the retroarticular region and the fetal tympanosquamosal fissure are shown. The anterior tympanic artery has a variable origin. In most cases, it originates from the maxillary artery; in other cases it originates from the superficial temporal artery or the bifurcation of the external carotid artery. On its way through the retroarticular region, it gives branches to the posterior part of the temporomandibular joint. It progresses along the most lateral part of the tympanosquamosal fissure, dividing into three branches that extend throughout the middle ear. A number of venous spaces in the retroarticular region that constitute the retrodiscal venous plexus. Small venous vessels along the fetal tympanosquamosal fissure accompany the anterior tympanic artery and drain into the retrodiscal venous plexus. CONCLUSIONS: During human fetal development, there is a wide connection across the tympanosquamosal fissure between the middle ear and the temporomandibular joint region. The anterior tympanic artery and its branches, as well as small venous vessels that are connected with the retrodiscal venous plexus, extend along the most lateral part of the fissure. PMID- 9973123 TI - Elevated levels of human salivary epidermal growth factor after oral and juxtaoral surgery. AB - PURPOSE: Saliva provides a natural reservoir of growth factors whose purposes have remained elusive. Animal studies suggest that saliva-derived growth factors play a role in systemic and oral wound healing. In the current study, salivary concentrations of epidermal growth factor (EGF) were monitored in patients before and after oral and juxtaoral surgery. PATIENTS AND METHODS: Whole resting saliva was collected from a group of patients with parotid gland tumors requiring surgical resection. Another group of patients a history of periodontal disease requiring surgical intervention also provided whole salivary samples. Healthy age and sex-matched persons served as controls. RESULTS: Salivary EGF levels were elevated in both groups of patients within 24 hours after surgery. In the periodontitis patients, a second smaller peak was assayed noted between 36 and 48 hours. After this, EGF concentrations returned to levels comparable to healthy controls in both experimental groups. CONCLUSIONS: Although the local cells have the ability to synthesize and secrete growth factors at a site of injury, these results suggest that surgery stimulates increased synthesis and secretion of growth factors in the saliva as well. This increased level of saliva-derived growth factor may also aid in promoting wound healing. PMID- 9973124 TI - Periosteal and galeal adhesiveness after a forehead lift in a rodent model. AB - PURPOSE: The aim of this study was to determine the strength of periosteal and galeal adhesiveness at particular intervals after subperiosteal and subperiosteal subgaleal forehead lifting in a rodent model. MATERIALS AND METHODS: Sixty mice underwent a subperiosteal or subperiosteal-subgaleal coronal forehead lift procedure. Necropic and histologic examination of the periosteal, galeal, and bone interface was performed on postoperative days 2, 4, 6, 8, and 10, and the strength of the elevated flap reattachment to underlying tissues was measured. RESULTS: Tension analysis in the early postoperative period showed a higher avulsive force was required to re-elevate subgaleal-subperiosteal flaps than subperiosteal flaps. However, subperiosteal flap adhesiveness appeared to increase rapidly between postoperative days 4 and 8. By day 10, the force required to re-elevate subperiosteal flaps was significantly higher than that required for subgaleal-subperiosteal flaps (P < or = .0001). Histologic analysis showed an inflammatory response at the periosteum-bone interface, which maximized at postoperative day 6. CONCLUSIONS: In the early postoperative period, subgaleal subperiosteal flaps had higher adhesiveness than subperiosteal flaps. However, by postoperative day 10, subperiosteal forehead flaps were substantially more adherent in this rodent model. PMID- 9973126 TI - Sickle cell disease: a review and update of current therapy. PMID- 9973125 TI - Ultrastructural study on adhesions in internal derangement of the temporomandibular joint. AB - PURPOSE: This study examined the ultrastructural characteristics of adhesions in the upper joint compartment of temporomandibular joint (TMJ). MATERIALS AND METHODS: Tissue biopsy specimens of adhesions were obtained during arthroscopic operation on 36 joints in 22 patients with internal derangement (ID). The biopsy specimens were examined by light and transmission electron microscopy. RESULTS: Adhesions were grossly divided into two types based on arthroscopic observation: 1) a band-like type, which connected the articular fossa and TMJ disc, and 2) a pseudowall-like type, which faced the synovial fluid and was lined by articular tissue. Two types of collagen arrangement were observed at the electron microscopic level: orderly arranged collagen bundles and randomly arranged collagen bundles. Orderly arranged collagen bundles were prominent in the band like adhesions. In pseudowall-like adhesions, mainly the randomly arranged collagen bundles were seen. However, in some dense fiber parts, orderly arranged collagen bundles also were observed. In other pseudowall-like adhesions, only orderly arranged collagen bundles were seen. Elastic fibers were abundant in some pseudowall-like adhesions with randomly arranged collagen bundles. There were no elastic fibers in the band-like adhesions, some dense fiber parts of the pseudowall-like adhesion, pseudowall-like adhesions consisting of only orderly arranged collagen bundles, and in the synovial membrane. CONCLUSION: The different arrangement of collagen fibers and presence or absence of elastic fibers were observed in the two types of adhesions. These findings served to show that extracellular components correspond to a dysfunction involving an ID of TMJ. PMID- 9973127 TI - Large radiolucent lesion of the maxilla. PMID- 9973128 TI - Iatrogenic osteonecrosis of the maxilla caused by laser injury. PMID- 9973129 TI - Metastatic squamous cell carcinoma of the nasal tip: a case report. PMID- 9973130 TI - Cardiac asystole during arthroscopic surgery of the temporomandibular joint: a case report. PMID- 9973131 TI - Distraction osteogenesis of the mandible using a submerged intraoral device: a report of three cases. PMID- 9973132 TI - Traumatic facial artery aneurysm: case report. PMID- 9973134 TI - Trephination in the treatment of scalp avulsion: successful application of a historical method. PMID- 9973133 TI - Life-threatening, delayed epistaxis after surgically assisted rapid palatal expansion: a case report. PMID- 9973135 TI - A simple technique for intraoral drain placement and fixation. PMID- 9973136 TI - Surgical exposure and bracketing technique for uprighting impacted mandibular second molars. PMID- 9973137 TI - Clarification of diagnostic criteria for ameloblastic fibroma. PMID- 9973138 TI - I before E, especially after T. PMID- 9973139 TI - Influence of sperm plasma membrane destruction on human sperm head decondensation and pronuclear formation. AB - This study investigated the ability of membrane-damaged sperm to undergo sperm head decondensation and male pronuclear forrmation following intracytoplasmic sperm injection. For induction of membrane-damage, sperm were exposed to 0.1% Triton X-100 for a few seconds. The single sperm curling (SSC) test was performed to evaluate the viability of the sperm. Of the injected oocytes 49 and 47% developed male pronuclei in the experimental and control groups, respectively. Sperm head decondensation was much higher in the membrane-damaged group (84 versus 70%). This study clearly shows that ICSI of membrane-damaged sperm does not affect pronuclear formation, although sperm head decondensation is much higher. PMID- 9973140 TI - Male fertility of kidney transplant patients with one to ten years of evolution using a conventional immunosuppressive regimen. AB - The reproductive functions and hormone serum levels of 55 male kidney transplant recipients were assessed. Patients underwent peritoneal dialysis before transplantation and were given immunosuppressive therapy afterward for 1 to 10 years. Spermatobioscopies were performed, and serum urea, creatinine, luteinizing hormone (LH), follicle-stimulating hormone (FSH), prolactin (PRL), and testosterone (T) levels were determined. Average serum urea and creatinine levels were 54.6+/-1.4 and 3+/-1.3 mg/dL, respectively. The average serum hormone levels were 3.2+/-2 mIU/mL (LH), 6.3+/-1.7 mIU/mL (FSH), 11.7+/-1.5 ng/mL (PRL), and 23+/-1.4 pg/mL (T). Libido reduction was reported in 88% of patients within 8 months following transplantation. Normozoospermia was seen in 47.3% of the patients, asthenozoospermia in 18.2% oligozoospermia in 14.5%, while oligoteratozoospermia, asthenoteratozoospermia, oligoasthenozoospermia, oligoasthenoteratozoospermia, and azoospermia were seen in the rest. Twenty-six patients procreated one or more children after transplantation; 36.6% of those children were premature but nonetheless healthy. No association existed between the post-transplant period and urea or creatinine levels. Significant differences were found when LH levels and sperm motility were assessed. Also, statistically significant differences were found when duration of dialysis, FSH levels, sperm counts, morphology, and motility between posttransplant fertile and infertile patients were correlated. In conclusion, there was an adequate recovery of sexual and reproductive functions in most patients subjected to kidney transplantation and conventional immunosuppressants. PMID- 9973141 TI - Semen culture, leukocytospermia, and the presence of sperm antibodies in seminal hyperviscosity. AB - Seminal hyperviscosity is generally thought to reveal genitourinary infection. The aim of the present work was to study this hypothesis. A total of 65 semen samples were obtained from males presenting for infertility screening. The samples were evaluated according to WHO criteria and microbiologically investigated, including culturing for Mycoplasma hominis and Ureaplasma urealyticum, and microscopic observation of Chlamydia trachomatis by a direct fluorescence assay. Determination of local antisperm antibodies was performed. Semen was categorized according to consistency: normal (n = 31) and high (n = 34). No difference was recorded either in the number of positive cultures, or in the number of species found in each sample. The number of white blood cells and the percentage of antibody-bound sperm showed no difference in the groups under study. There was no association between seminal hyperviscosity, positivity in semen cultures, number of species isolated in semen cultures, leukospermia, or presence of sperm antibodies. Further studies should be performed considering the evolution of the genital-infected patients to clarify the etiology of the hyperviscosity. PMID- 9973142 TI - Semen analysis in men from Merida, Venezuela, over a 15-year period. AB - To determine the possible changes in semen quality of Venezuelan men from 1981 to 1995, a retrospective analysis of semen volume and sperm concentrations was carried out for 2313 men from infertile couples. According to the sperm counts the sample was categorized in four groups: A, 0 sperm; B, <20 x 10(6) sperm/mL; C, 20-200 x 10(6) sperm/mL; D, 2200 x 10(6) sperm/mL. The percentage of men in each group was 9.1, 18.8, 63. 1, and 9.0%, respectively. The frequency of azoospermia and oligozoospermia (groups A and B) did not change over the last 15 years. On the contrary, the frequency showed a significant increase in group C and a decrease in group D. The range of the means of semen volume was 2.6-3.6 mL, linear regression analysis did not show a decrease in seminal fluid volume over time. The range of the means of sperm concentrations were 6.2-12.0 x 10(6) sperm/mL, 73-100 x 10(6) sperm/mL), and 230-340 sperm x 10(6)/mL in groups B, C, and D, respectively. Linear regression analysis revealed a significant reduction in the means of sperm concentrations only in group D. Excluding the azoospermic group, the analysis of pooled data (B + C + D), did not show a significant change in the means of sperm density throughout time. In the semen samples with sperm counts below 200 x 10(6)/mL the means of sperm concentration did not change in the 15-year period of observation. PMID- 9973143 TI - Aggregation of human sperm at higher temperature is due to hyperactivation. AB - Chemotaxis of sperm cells to chemicals and hormones, such as progesterone, helps us to understand the concept of sperm transport. Here, the hypothesis was that heat increased sperm hyperactive motility, which caused the sperm to aggregate at the higher temperature. The objectives were (1) to determine the concentration of sperm at both halves of an artificial female reproductive tract made from a hermetically sealed cryopreservation straw filled with culture medium and placed with each end at different temperatures, and (2) to analyze the motility or kinematic parameters and hyperactivation of sperm found at the different temperatures. Cryopreserved-thawed human donor sperm (N = 6) were pooled and processed through 2-layer colloid solution. Analyses of the motile sperm were carried out and the washed sperm were homogeneously mixed and pipetted into several 0.5-mL French cryopreservation straws and heat-sealed. The control substance, consisting of acid-treated sperm, was also placed in several straws. The plastic straws of sperm were placed half at 23 degrees C and half was at either 37 or 40 degrees C. After 4 h, sperm at different sections of the straws were analyzed using the Hamilton Thorn motility analyzer (HTM-C). After 4 h of incubation, the concentration of sperm was doubled at the 40 degrees C heated half of the straw when compared with the other half of the straw at 23 degrees C. There were no differences in sperm concentration in the straw kept half at 37 degrees C and half at 23 degrees C. There were significantly higher percent motility, mean average path velocity, straight line velocity, lateral head displacement, and percent hyperactivation in sperm at the 40 degrees C temperature. The aggregation of sperm at the higher temperature of 40 degrees C may be due to enhanced motility, increased sperm velocities, and a 10-fold increase in hyperactivation at that temperature. The 37 degrees C temperature was not sufficient to attract sperm. Sperm cells migrating into the higher temperature site of ovulation begin nonprogressive hyperactivation movement, which is the physiological "brake" to detain the sperm at the site of ovulation. PMID- 9973144 TI - Chlamydia trachomatis detected by ligase chain reaction in the semen of asymptomatic patients without pyospermia or pyuria. AB - To determine whether an absence of leukocytes in semen and urine predicts an absence of Chlamydia trachomatis in asymptomatic infertile men, chlamydial DNA was detected in subjects' semen and urine by ligase chain reaction (LCR). Ninety eight infertile men were studied, including 39 cases of oligozoospermia, 19 of azoospermia, 16 of asthenozoospermia, and 24 of normozoospermia. None of the subjects had pyospermia or pyuria. C. trachomatis was detected by LCR. Antichlamydial and antisperm antibody were also measured. C. trachomatis was detected by LCR in the semen of only 1 of 98 patients (1.02%), but not in the urine samples. In C. trachomatis-positive patients LCR, IgG, and IgA levels were higher than normal. No antisperm antibody was detected. Even if leukocytes are not observed in the semen and urine of asymptomatic infertile men, the presence of C. trachomatis in semen specimens is rarely observed. Therefore, it should be noted that the presence of C. trachomatis in such cases is addressed in the context of artificial insemination and other assisted reproductive technologies. PMID- 9973146 TI - Lumping or splitting autoimmune rheumatic disorders? Lessons from Sjogren's syndrome. PMID- 9973145 TI - Physioanatomic entirety of external anal sphincter with bulbocavernosus muscle. AB - Stimulation of the glans penis evokes contraction of both the bulbocavernosus muscles (BCM) and the external anal sphincter (EAS). This synchronous contraction of the two muscles led us to study their physioanatomic relationship and possible role in erection and ejaculation. Fifteen male cadavers were studied (8 neonatal deaths and 7 adults; mean age 48 years) by dissection. The bulbocavernosus reflex action was performed in 12 healthy male volunteers (mean age 37 years) before and after anesthetizing the EAS. The response of the EAS and BCM to inferior rectal nerve stimulation was assessed in 6 men (mean age 41 years). The superficial fibers of the base loop of the EAS extended forward to the penile bulb where they were arranged into 3 groups: 1 median and 2 lateral. The median fibers, or the "retractor penis muscle," were found inserted into the corpora cavernosa and the lateral fibers, or the "compressor bulbae muscle," into the perineal membrane. Upon glans penis stimulation, both the EAS and BCM contracted synchronously with similar latency and action potentials. During EAS anesthesia, the two muscles did not respond to glans penis stimulation. They contracted simultaneously with similar latency and action potentials upon inferior rectal nerve stimulation. The BCM is an integral part of the EAS, and the muscle in its entirety is appropriately named "anogenital muscle." The muscle plays a dual and synchronous role in fecal control and sexual response. PMID- 9973147 TI - The Heberden Oration 1997. Treatment of rheumatoid arthritis: from symptomatic relief to potential cure. PMID- 9973148 TI - Electron microscopy and capillaroscopically guided nailfold biopsy in connective tissue diseases: detection of ultrastructural changes of the microcirculatory vessels. AB - The aims of the study were to describe and compare the frequency and nature of histologically detectable microvascular lesions in patients with various connective tissue diseases (CTD). An electron microscopic examination of specimens obtained by the technique of capillaroscopically guided nailfold biopsy was performed in 52 patients with CTD [nine systemic lupus erythematosus (SLE), eight mixed CTD, 18 scleroderma, 17 undifferentiated CTD] and 27 controls. The microvascular changes most frequently observed by electron microscopy were multilayering of the basal lamina (approximately 70% of the CTD patients), an increased amount of perivascular connective tissue, perivascular oedema formation, and an increased number of perivascular fibroblasts and mast cells (each in 30-37% of the CTD patients). In contrast, no particular histopathological feature was found in > 25% of the controls, multilayering (22.6%) being the most frequently observed. Comparing the different conditions studied, there were distinct differences in the frequency and nature of the histologically observed microvascular changes. In particular, SLE seems to be based on a separable type of vasculopathy consisting of significantly less frequent microvascular abnormalities. In conclusion, ultrastructural abnormalities of the microvascular system are a frequent finding in CTD. Electron microscopic examination of specimens obtained by capillaroscopically guided nailfold biopsy is able to disclose histopathological differences between defined entities. Therefore, this approach may be a useful tool to gain further insights into potentially separable aetiopathological mechanisms of the various types of CTD. PMID- 9973149 TI - A randomized, double-blind, placebo-controlled study of moclobemide and amitriptyline in the treatment of fibromyalgia in females without psychiatric disorder. AB - OBJECTIVE: To study the usefulness of moclobemide and amitriptyline in the treatment of fibromyalgia (FM) in females without psychiatric disorder. METHODS: In the present four centre, 12 week study, 130 female FM patients not suffering from psychiatric disorders were randomized to receive amitriptyline (AMI; 25 37.5 mg), moclobemide (MOCLO; 450-600 mg) or identical placebo. RESULTS: Seventy-four, 54 and 49 per cent of patients on AMI, MOCLO and placebo, respectively, were judged as responders. The patients on AMI also managed best regarding the respective improvements during the trial in general health, pain, sleep quality and quantity, and fatigue on visual analogue scales (VAS), the areas of the Nottingham Health Profile (NHP), as well as in the three Sheehan's functional disability scales. In the within-group comparisons, MOCLO also improved pain assessed both on VAS and on the NHP pain dimension, but the improvement was invalidated by the poor success of the drug with regard to sleep. The tolerabilities of all three drugs were comparable. CONCLUSION: The study indicates that MOCLO may not be helpful in FM patients free from clinically meaningful psychiatric problems. PMID- 9973150 TI - Antineutrophil cytoplasmic antibodies in primary Sjogren's syndrome: prevalence and clinical significance. AB - OBJECTIVE: To evaluate the prevalence of cytoplasmic (c) and perinuclear (p) antineutrophil cytoplasmic antibodies (ANCA) in patients with primary Sjogren's syndrome (SS), and to correlate the presence of ANCA with extraglandular and immunological manifestations related to SS. METHODS: In a cross-sectional study, we included 82 consecutive patients (75 female and seven male; mean age 61 yr; range 33-87 yr) attending our unit. All patients fulfilled four or more of the diagnostic criteria for SS proposed by the European Community Study Group in 1993. Extraglandular manifestations such as arthralgia and/or arthritis, Raynaud's phenomenon, autoimmune thyroiditis, peripheral neuropathy, renal involvement and cutaneous vasculitis were also recorded. Serum samples were examined by indirect immunofluorescence (IIF) and by ELISA using as substrates myeloperoxidase (MPO) and proteinase 3 (PR3). RESULTS: ANCA were detected in nine (11%) patients: seven had pANCA and two an atypical pattern. These two atypical ANCA became cANCA when paraformaldehyde fixation was applied. ELISA findings showed that two patients had antibodies against MPO, and no patient had antibodies to PR3. The most common extraglandular manifestations in the ANCA positive patients were articular involvement in six (66%) patients, peripheral neuropathy in five (55%), Raynaud's phenomenon in four (44%) and cutaneous vasculitis in four (44%). Of the four patients with cutaneous vasculitis and ANCA, two had a mononuclear inflammatory vascular disease (MIVD) in the biopsy specimen. When compared with patients without ANCA, those with these antibodies had a higher prevalence of cutaneous vasculitis (44% vs 8%, P = 0.01), Raynaud's phenomenon (44% vs 8%, P = 0.01) and peripheral neuropathy (55% vs 7%, P < 0.001). CONCLUSION: ANCA positivity can be found in patients with primary SS and its detection is associated with the presence of clinical manifestations attributable to vascular involvement (cutaneous vasculitis, peripheral neuropathy and Raynaud's phenomenon). PMID- 9973152 TI - The relevance of large-vessel vascular disease and restricted ankle movement to the aetiology of leg ulceration in rheumatoid arthritis. AB - Leg ulceration in rheumatoid arthritis (RA) without systemic vasculitis is a difficult clinical problem and a common cause of morbidity. We have assessed venous function, arterial pressures and range of ankle movement in 23 RA patients with a leg ulcer and compared the results with those in the non-ulcerated contralateral limb and in 25 RA patients matched for age and duration of arthritis. We found evidence of venous insufficiency in RA ulcer patients compared to disease controls. Ankle movement was more restricted in the ulcerated limb compared to the non-ulcerated contralateral leg. There was no difference in large-vessel arterial function between groups. These findings have implications for therapy and rates of healing. PMID- 9973151 TI - GB virus C in systemic medium- and small-vessel necrotizing vasculitides. AB - BACKGROUND: Vasculitides are diseases of unknown origin in the majority of cases, but sometimes are the consequence of viral infections; for instance, hepatitis B virus (HBV)-related polyarteritis nodosa (PAN) or hepatitis C virus (HCV) associated cryoglobulinaemia. OBJECTIVE: To investigate the role of hepatitis G or GB virus C (GBV-C) in various forms of medium- and small-vessel vasculitides. DESIGN: Retrospective analyses of sera. SETTING: Tertiary care hospital in Bobigny, France. PATIENTS: Fifty-six vasculitides: 19 HBV-PAN, 10 PAN without HBV infection, 11 microscopic polyangiitis (MPA), seven Churg-Strauss syndrome (CSS) and nine Wegener's granulomatosis (WG). Every sample was collected before treatment. MEASUREMENTS: GBV-C RNA was detected using a reverse transcription polymerase chain reaction assay with primers derived from the conserved GBV-C helicase and NS5a regions. RESULTS: GBV-C was detected in five of the 56 samples (8.9%): four patients with HBV-related PAN and one with MPA; three of these patients (two with HBV-PAN, one with MPA) had been transfused and two HBV-PAN were i.v. drug addicts. GBV-C was not found in CSS or in WG. CONCLUSION: GBV-C infection was observed only in patients who had been transfused or who were addicts. This virus is unlikely to have a primary role in vasculitides. PMID- 9973153 TI - IgA class serum antibodies against three different Klebsiella serotypes in ankylosing spondylitis. AB - OBJECTIVE: To investigate the possible predominance of certain Klebsiella pneumoniae capsular types in the pathogenesis of ankylosing spondylitis (AS). METHODS: The prevalence of IgA class antibodies against three different K. pneumoniae strains (with capsular types 21, 30 and 43) was studied in the sera of 177 patients with AS and of 100 healthy blood donors using an enzyme-linked immunosorbent assay. RESULTS: The median Klebsiella-specific antibody levels were always higher in patients than in controls regardless of the serotype used as antigen. When the prevalence of increased antibody levels was compared between the groups, it was highest against the strain with capsular type 30, whereas against strains 21 and 43 it was similar among patients and controls. CONCLUSIONS: A broad range of Klebsiella serotypes may be involved in the pathogenesis of AS. Thus, it is important to take the different Klebsiella serotypes into particular account in these studies. PMID- 9973154 TI - Serum levels of vascular endothelial growth factor (VEGF) are markedly elevated in patients with Wegener's granulomatosis. AB - OBJECTIVES: Necrotizing vasculitis and granuloma formation are the predominant features of Wegener's granulomatosis (WG). We have investigated the importance of vascular endothelial growth factor (VEGF) in monitoring disease activity in WG. METHODS: Serum VEGF levels were determined in 23 patients with active WG, 21 healthy controls and 25 patients with urinary infection, by ELISA using commercially available antibodies to VEGF. RESULTS: VEGF levels were enormously elevated in patients with WG compared to both controls and patients with urinary infection (P < 0.0001). Of the 23 patients, 21 (91.3%) had VEGF levels above the cut-off value (3.3 ng/ml, calculated as the mean of the controls + 2 S.D.). Further analysis of the data showed that VEGF levels did not correlate with age, sex, incidence of classic antineutrophil cytoplasmic antibodies (c-ANCA) or duration of the disease (P > 0.05), but there was correlation with disease activity (r = 0.51, P < 0.01). VEGF levels were higher in patients with major compared to those with minor disease activity (P < 0.01). However, there was no significant correlation between VEGF levels and the Birmingham scores for vascular activity and damage. CONCLUSION: VEGF levels are raised in WG patients compared to normal controls and may be a marker of disease activity. Further studies on serial blood samples from a large cohort of patients with WG and other systemic vasculitides are needed to evaluate the specificity and usefulness of VEGF levels in monitoring disease activity. PMID- 9973155 TI - A new antibody in rheumatoid arthritis targeting glycated IgG: IgM anti-IgG-AGE. AB - Hyperglycaemia and/or oxidative stress can cause IgG to be modified by advanced glycation end products (AGE). Three patients with aggressive rheumatoid arthritis (RA) and vasculitis are described who have high titres of IgM antibodies against AGE-modified IgG (IgM anti-IgG-AGE). Diabetics and randomly selected patients with rheumatic diseases, including 50 additional RA patients, were tested for IgM and IgA anti-IgG-AGE by ELISA. AGE-modified proteins were detected using the nitroblue tetrazolium (NBT) colorimetric method. The presence of Nepsilon (carboxymethyl) lysine, an AGE modification, was detected on IgG-AGE by immunoblotting. A total of 20/41 (49%) rheumatoid factor (RF)-positive RA patients tested had IgM anti-IgG-AGE antibodies, 4/12 (33%) RF-positive systemic lupus erythematosus (SLE) patients, 3/5 RF-positive patients with primary Sjogren's syndrome (SS), and 3/5 RF-positive diabetics. All patients with RF negative RA, SLE, SS, osteoarthritis (24), spondyloarthritis (15), adult-onset Still's disease (8), diabetes (25) and healthy controls (20) were anti-IgG-AGE negative. RF and IgM anti-IgG-AGE appeared to be a linked response. The IgM anti IgG-AGE, along with IgG-AGE, may contribute to the pathogenesis of RA. PMID- 9973156 TI - Long-term outcomes of an arthritis self-management programme. AB - OBJECTIVE: A previous UK evaluation of the Arthritis Self-Management Programme (ASMP) demonstrated 4 month improvements in physical and psychological well-being including increased arthritis self-efficacy and increased use of self-management behaviours such as cognitive symptom management, and reductions in pain, fatigue and anxiety. The purpose of this study was to determine whether these effects were maintained at 12 month follow-up. METHODS: Twelve month data were collected via self-administered questionnaires mailed to participants who had previously responded prior to attending the ASMP and at 4 months follow-up. RESULTS: The sample (n = 112) comprised 82% women with a mean age of 59.6 (S.D. 12.4) yr and a mean disease duration of 14.9 (S.D. 11.1) yr. The majority of participants had a general practitioner-recorded diagnosis of either rheumatoid arthritis (46%) or osteoarthritis (44%). Many of the changes noted at 4 months were sustained at the 12 month follow-up. CONCLUSION: This first long-term evaluation of a community based patient education intervention delivered in the UK suggests that after participation in the ASMP, persons with arthritis derive substantial and prolonged benefits in terms of perceived ability to manage arthritis, reduction in pain and improved psychological well-being. PMID- 9973157 TI - A study of the frequency of pericardial and pleural effusions in scleroderma. AB - OBJECTIVE: To determine the frequency of pericardial and pleural effusions in scleroderma. METHODS: Using a case-control format, patients with scleroderma and no known cardiac disease were recruited. Echocardiograms and chest radiographs were performed. Age- and gender-matched controls had echocardiograms performed which were read by a cardiologist, blinded to the diagnosis. The medical records of 60 other scleroderma patients were also reviewed. RESULTS: Thirty-seven scleroderma subjects were recruited, of whom 18 had diffuse disease. Only eight subjects with diffuse disease and five with limited scleroderma had normal echocardiograms compared to 20 of 37 controls (P < 0.1). Two had pericardial effusions, both with diffuse scleroderma, and none of the controls had effusions present. Pulmonary hypertension occurred in three with diffuse disease and no controls. A chart review of a further 60 patients with scleroderma was performed. Pleural effusions were identified in 7% (4/58) of the cohort of scleroderma patients and were more frequent in diffuse disease (10%). A total of 17% (4/23) of diffuse and 4% (1/23) of limited scleroderma patients had evidence of pericardial effusions. CONCLUSIONS: Pericardial effusions do occur in scleroderma without evidence of clinical cardiac dysfunction and are more common in diffuse scleroderma. Pleural effusions in scleroderma occur less frequently, in 70%. PMID- 9973158 TI - Clinical course and remission rate in patients with early rheumatoid arthritis: relationship to outcome after 5 years. AB - OBJECTIVE: To investigate the clinical course in early rheumatoid arthritis (RA) patients followed prospectively, to relate course to outcome after 5 yr, and to try to identify prognostic features. METHODS: A total of 183 patients with definite RA and a mean disease duration of 11 months were included. Of these, 75% were rheumatoid factor (RF) positive; 85% carried the shared epitope, 32% on both alleles. Most patients were assessed every 6 months. Disability was evaluated with the Health Assessment Questionnaire (HAQ) and radiographic findings according to Larsen. Remission was defined in two ways: with the American Rheumatism Association (ARA) criteria and as 'no arthritis at least at one follow up visit'. RESULTS: Twenty per cent achieved ARA-defined remission periods of at least 6 months duration; 21 were spontaneous and 18 drug induced. Average length of remission was 20.5 months. The remission periods constituted 7% of follow-up for all patients. Another 36% achieved remission according to the second definition. All 56% were considered to have a relapsing-remitting disease pattern, in contrast to the remaining 44% with a persistent disease pattern. More patients with persistent disease were treated with disease-modifying anti rheumatic drugs (DMARDs) and had also received a larger number of different drugs. Outcome after 5 yr regarding disability, joint inflammation and joint damage was worse for patients with persistent disease. Neither ARA-defined remission nor disease pattern could be accurately predicted. CONCLUSIONS: Long term ARA-defined remission was rare, constituting 7% of follow-up for the entire cohort. For those 20% achieving remission, this period represented 34% of their follow-up. A total of 56% had a relapsing-remitting disease pattern and 44% had a persistent disease pattern. This classification had prognostic implications with persistency being a bad prognostic sign. PMID- 9973159 TI - Antibodies to Klebsiella pneumoniae lipopolysaccharide in patients with ankylosing spondylitis. AB - The role of microbial lipopolysaccharides (LPS) in the aetiopathogenesis of ankylosing spondylitis (AS) is a matter of continuing debate. In this study, class-specific IgG, IgA and IgM antibodies against Klebsiella pneumoniae, Escherichia coli, Salmonella typhimurium and Salmonella enteritidis LPS were measured by enzyme-linked immunosorbent assay (ELISA) in 100 AS patients, 50 rheumatoid arthritis (RA) patients and 50 healthy control subjects. The AS patients had significantly elevated levels of IgG and IgA antibodies against K. pneumoniae LPS (P < 0.001) and IgA antibodies against E. coli LPS (P < 0.05) compared to healthy controls. There were no significant elevations of antibody levels against S. typhimurium and S. enteritidis in the three study groups. In addition, there was a correlation between IgG and IgA anti-K. pneumoniae LPS antibody levels and the acute-phase reactant C-reactive protein (P < 0.001). PMID- 9973160 TI - Circulating interleukin-16 in systemic lupus erythematosus. AB - OBJECTIVE: To investigate the relationship between interleukin (IL)-16 and systemic lupus erythematosus (SLE). METHODS: Serum levels of IL-16 were examined in SLE patients using an enzyme-linked immunosorbent assay (ELISA). RESULTS: The serum level of IL-16 in the patients was much higher than that in healthy volunteers (P < 0.001). An increase in IL-16 was observed in proportion to the activity of SLE assessed by the SLE Disease Activity Index (SLEDAI) score (P < 0.0001). CONCLUSIONS: Our observations suggest an interaction between disease activity and the production of IL-16 in SLE, and reveal that IL-16 is a useful indicator of disease activity. This is the first report describing the relationship between IL-16 and SLE. PMID- 9973161 TI - Benefit of 6 months long-term physical training in polymyositis/dermatomyositis patients. AB - OBJECTIVE: The benefit of long-term physical training in patients with chronic polymyositis or dermatomyositis (PM/DM) was studied prospectively. METHODS: Eight patients with chronic PM/DM participated in a training programme for 6 months. A group of five PM/DM patients without any physical training was observed for control purposes. RESULTS: While there was no significant change in serum creatine phosphokinase (CPK) levels, the 'activities of daily living (ADL)' score improved significantly (P < 0.03), peak isometric torque (PIT) generated by muscle groups in the lower extremities rose significantly (P < 0.03) and there was a statistically highly significant increase in peak oxygen uptake (VO2max) relative to body weight (P < 0.02) due to the long-term training. The patients improved their aerobic capacity by 28%, which is clinically significant. In the untrained patients, no improvement in these target parameters was observed. CONCLUSION: In clinically stable DM/PM patients, long-term physical training can safely be performed and is recommended as part of a comprehensive rehabilitation management, particularly in view of the cardiopulmonary risk in these patients. PMID- 9973162 TI - Post-streptococcal reactive myalgia: a novel syndrome secondary to infection with group A or G streptococci. PMID- 9973163 TI - Hypothyroid myopathy as a complication of interferon alpha therapy for chronic hepatitis C virus infection. AB - Interferon alpha (IFN-alpha) therapy is associated with a number of immunological side-effects, including autoimmune diseases and a 10% prevalence of thyroiditis. Hepatitis C virus (HCV) infection itself predisposes to autoimmune phenomena including hypothyroidism and myositis. The development of clinical hypothyroidism in the presence of positive thyroid antibodies in patients infected with HCV and treated with IFN-alpha suggests a possible association between the viral disease and the therapy. HCV infection may predispose to autoimmune thyroid disease and IFN-alpha therapy may secondarily lead to the development of thyroid dysfunctions. We report the single case of a female patient who developed a severe proximal myopathy in conjunction with primary hypothyroidism (Hoffmann's syndrome) secondarily to IFN-alpha therapy for HCV infection. This case highlights the need for careful clinical and biological monitoring for potential side-effects in such patients. PMID- 9973164 TI - Digital gangrene and anticentromere antibodies without scleroderma. PMID- 9973165 TI - Sternum tumour revealing a chronic myeloid leukaemia. PMID- 9973166 TI - Unusual occurrence of acute low back pain in a patient with ruptured urachal cyst. PMID- 9973167 TI - Cerebral calcification in a patient with systemic lupus erythematosus and a monoclonal IgG reactive with glial fibrillary acidic protein. PMID- 9973168 TI - Haemophagocytic syndrome in a patient with dermatomyositis. PMID- 9973169 TI - Successful treatment with antithymocyte globulin and cyclosporin A of a severe aplastic anaemia associated with an eosinophilic fasciitis. PMID- 9973170 TI - Aortitis in relapsing polychondritis. PMID- 9973171 TI - Infection with an unenveloped DNA virus (TTV) associated with non-A to G hepatitis in patients with rheumatoid arthritis. PMID- 9973172 TI - Outcome in systemic vasculitis. PMID- 9973173 TI - Sensorineural hearing loss, iritis and ankylosing spondylitis. PMID- 9973174 TI - Effector pathways regulating T cell activation. AB - Activation of T lymphocytes is a key event for an efficient response of the immune system. It requires the involvement of the T cell receptor antigen as well as costimulatory molecules such as CD28. Engagement of these receptors through the interaction with a foreign antigen associated with major histocompatibility complex molecules and CD28 counter-receptors B7.1/B7.2, respectively, results in a series of signaling cascades acting in synergy and which culminate in activation of interleukin-2 gene transcription and eventually cell proliferation. Many studies aimed at characterizing these specific effector pathways have been published; however, the actual signaling molecules that transduce activation signals from the cell membrane to the nucleus and that directly regulate interleukin-2 gene transcription are not yet completely defined and remain a matter of debate. In this commentary, we have attempted to analyze the results, which are sometimes diverging if not totally contradictory, characterizing effector pathways that possibly are triggered during T cell activation. PMID- 9973175 TI - A necessary role for cell shrinkage in apoptosis. AB - The loss of cell volume is a fundamental and universal characteristic of programmed cell death. However, what was once thought to be a passive, secondary feature of the cell death process has now become an area of research interest. Recent studies have integrated cell volume regulation and the movement of ions with the activation of apoptosis. A dramatic reduction of potassium and sodium concentration has been shown to occur in apoptotic cells that exhibit a shrunken morphology. Furthermore, maintaining the normal physiological intracellular concentration of monovalent ions, particularly potassium, inhibits the activation and activity of the death cascades. Thus, the role ions play during apoptosis is more extensive than just facilitation of the loss of cell volume. In this article, we will review the concepts of cell volume regulation and the loss of volume during apoptosis. Additionally, we will underscore our current understanding of ion movement as it relates to the activation of the cell death process. PMID- 9973176 TI - Interaction between glucocorticoids and beta2-agonists: alpha and beta glucocorticoid-receptor mRNA expression in human bronchial epithelial cells. AB - Recent studies have suggested that regular use of beta2-agonists has adverse effects on asthma control, due to the cross-talk between cAMP responsive element binding proteins (CREB) and glucocorticoid receptors (GR). The aim of this study was to investigate the interaction between GR and CREB on cytoplasmic protein level with a gel mobility shift assay and to determine the effect of this interaction on mRNA levels by Northern blot analysis. After exposing human bronchial epithelial cells for 1 hr to either 1 microM terbutaline or budesonide, more binding of CREB and GR, respectively, was observed to their responsive elements in DNA. Simultaneous exposure to terbutaline and budesonide also increased the binding of CREB and GR to DNA. After 4 hr, both alpha and beta GR mRNAs were down-regulated by 1 microM budesonide. Simultaneous addition of 1 microM terbutaline prevented this down-regulation. Adding 100 times more budesonide compared to terbutaline again down-regulated both GR forms, although significantly less compared to the down-regulation induced by 1 microM budesonide alone. Addition of terbutaline to cells already exposed to budesonide did not reverse the GR mRNA expression within 44 hr. Similar results were obtained with metallothionein-2 (MT2) mRNA levels. In conclusion, beta2-agonists interfere with the GR function in human bronchial epithelial cells when given simultaneously, with this being overcome by sequential exposure of the cells to first glucocorticoids and later beta2-agonists. PMID- 9973177 TI - Early modulation of genes encoding peroxisomal and mitochondrial beta-oxidation enzymes by 3-thia fatty acids. AB - The aim of the present study was to elucidate the effects of a single dose of 3 thia fatty acids (tetradecylthioacetic acid and 3-thiadicarboxylic acid) over a 24-hr study period on the expression of genes related to peroxisomal and mitochondrial beta-oxidation in liver of rats. The plasma triglyceride level decreased at 2-4 hr, 4-8 hr, and 8-24 hr, respectively, after a single dose of 150, 300, or 500 mg of 3-thia fatty acids/kg body weight. Four to eight hours after administration of 3-thia fatty acids, a several-fold-induced gene expression of peroxisomal multifunctional protein, fatty acyl-CoA oxidase (EC 1.3.3.6), fatty acid binding protein, and 2,4-dienoyl-CoA reductase (EC 1.3.1.43) resulted, concomitant with increased activity of 2,4-dienoyl-CoA reductase and fatty acyl-CoA oxidase. The expression of carnitine palmitoyltransferase-I and carnitine palmitoyltransferase-II increased at 2 and 4 hr, respectively, although at a smaller scale. In cultured hepatocytes, 3-thia fatty acids stimulated fatty acid oxidation after 4 hr, and this was both L-carnitine- and L-aminocarnitine sensitive. The hepatic content of eicosapentaenoic acid and docosahexaenoic acid decreased throughout the study period. In contrast, the hepatic content of oleic acid tended to increase after 24 hr and was significantly increased after repeated administration of 3-thia fatty acids. Similarly, the expression of delta9-desaturase was unchanged during the 24-hr study, but increased after feeding for 5 days. To conclude, carnitine palmitoyltransferase-I expression seemed to be induced earlier than 2,4-dienoyl-CoA reductase and fatty acid binding protein, and not later than the peroxisomal fatty acyl-CoA oxidase. The expression of delta9-desaturase showed a more delayed response. PMID- 9973178 TI - Biochemical characterization of HIV-1 reverse transcriptases encoding mutations at amino acid residues 161 and 208 involved in resistance to phosphonoformate. AB - Mutations at amino acid residues 161 (Q161L) and 208 (H208Y) of the reverse transcriptase (RT) have been identified in HIV-1 variants which are resistant to phosphonoformate (PFA). In the present study, we report on the biochemical properties of recombinant RTs (rRTs) carrying either one or both of the above mutations. We also report on their susceptibility to PFA and to nucleoside (NRTI) and non-nucleoside (NNRTI) RT inhibitors. Like the wild-type (wt) enzyme, mutant rRTs H208Y and Q161L/H208Y showed a preference for Mg2+ over Mn2+, whereas the Q161L rRT preferred Mn2+. The three mutant rRTs showed degrees of PFA resistance which differed according to the template-primer used, and steady-state kinetic studies revealed an inverse correlation between their degree of PFA resistance, affinity for deoxynucleoside triphosphates (dNTPs) and catalytic efficiency (kcat/Km ratio). These results indicated that HIV-1 rRTs bearing mutations at codons 161 and/or 208 had altered dNTP binding sites which led to a PFA-resistant phenotype. However, unlike the corresponding mutant viruses, which are hypersensitive to 3'-azido-3'-deoxythymidine (AZT), 11-cyclopropyl-5,-11-dihydro 4-methyl-6H-dipyridol[3,2-b:2',3',-e] diazepin-6-one (Nevirapine) and (+)-(5S) 4,5,6,7-tetrahydro-5-methyl-6-(3-methyl-2-butenyl)-imidazo[4,5, 1 jk][1,4]benzodiazepin-2(1H)-thione. (TIBO R82150), the mutant RTs Q161L and Q161L/H208Y were resistant to 3'-azido-3'-deoxythymidine triphosphate (AZTTP) and as susceptible as the wt enzyme to Nevirapine and TIBO R82150. Overall, these results suggest that codons 161 and 208 of the HIV-1 RT gene are involved in substrate binding as well as in NRTI recognition, and provide more insights into the mechanism by which HIV-1 becomes resistant to PFA. PMID- 9973179 TI - The metabolism of 3-phenoxybenzoic acid-containing xenobiotic triacylglycerols in vitro by pancreatic, hormone-sensitive and lipoprotein lipases. AB - Two model substrates, rac-1-(3-phenoxy-[ring-14C]benzoyl)-2,3-dipalmitoyl glycerol (1(3PBA)DPG) and sn-2-(3-phenoxy-[ring-14C]benzoyl)-1,3-dipalmitoyl glycerol (2(3PBA)DPG), were compared with tri[1-14C]palmitoylglycerol or tri[9,10(n)-3H]oleoylglycerol as substrates for pancreatic lipase, lipoprotein lipase, and hormone-sensitive lipase. The loss of 3PBA from the sn-2 position was always low because of the positional specificity of the lipases. The loss of 3PBA from the rac-1 position was similarly low with hormone-sensitive lipase (about 7% of the loss of oleate), but higher with pancreatic lipase (about 35% that of oleate) and lipoprotein lipase (about 23% that of oleate). With one exception, more than 50% and up to 80% of the 14C-3PBA was still in the form of a diacylglycerol after incubation with a lipase, whereas free acid or monoacylglycerol forms would have been expected. Lipoprotein lipase acting on 1 (14C-3PBA)DPG produced nearly 70% of its product as nonesterified 3PBA and only 25% as the diacylglycerol. The results suggest that 3PBA-containing xenobiotic triacylglycerols, and the 3PBA-glycerol ester bond in particular, are poorer substrates for lipases than are their natural counterparts, with the result that high proportions of partially digested xenobiotic acylglycerols are produced. The three lipases performed differently with the xenobiotic substrates; this could have consequences for the relative rates of storage and clearance of the xenobiotic triacylglycerols from the body. PMID- 9973180 TI - The metabolism of the xenobiotic triacylglycerols, rac-1- and sn-2- (3 phenoxybenzoyl)-dipalmitoylglycerol, following intravenous administration to the rat. AB - The metabolism of 3-phenoxybenzoic acid (3PBA) in the form of triacylglycerol conjugates was compared with that of non-esterified 3PBA. Three radiolabeled triacylglycerols (rac-1-(3-phenoxy-[ring-14C]-benzoyl)-2,3-dipalmitoylglycerol (1(3PBA)DPG), sn-2-(3-phenoxy-[ring-14C]benzoyl)-1,3-dipalmitoylglycerol (2(3PBA)DPG) and the "natural" tri-[1-14C]oleoylglycerol) were incorporated into rat VLDL. Nonesterified 3PBA was prepared in rat serum albumin solution. Each preparation was administered i.v. to rats and serial blood samples were taken during the subsequent 6 hr. Urine and faeces were collected and tissue residues determined at 6 hr and 48 hr after administration. Biphasic elimination of 3PBA was observed with half-lives of 18 min and 2 hr. The triacylglycerols showed a rapid first phase and a longer second phase half-life: trioleoylglycerol 26 hr, 1(3PBA)DPG 7.6 hr and 2(3PBA)DPG 17.3 hr. The majority (63-76%) of 3PBA (whether esterified or not) was eliminated within 24 hr in urine, which contained similar profiles of metabolites. The triacylglycerols gave rise to higher tissue residues than did non-esterified 3PBA, particularly in adipose tissue which alone was not significantly depleted of radioactivity between 6 and 48 hr. The results accord with the rapid association of the VLDL-(3PBA)DPG complexes with lipoprotein lipase of the capillary epithelium, followed by hydrolysis to 3PBA, metabolism and elimination but with a proportion being redistributed into adipose tissue, re esterified and then eliminated relatively slowly. PMID- 9973181 TI - Effect of curcumin on the advanced glycation and cross-linking of collagen in diabetic rats. AB - A close association between increased oxidative stress and hyperglycemia has been postulated to contribute significantly to the accelerated accumulation of advanced glycation end products (AGEs) and the cross-linking of collagen in diabetes mellitus. In the present work, we report the influence of curcumin, an efficient antioxidant, on the level of AGEs and the cross-linking of collagen in diabetic rats. Diabetic rats were given curcumin (200 mg/kg body wt) orally for a duration of 8 weeks. The antioxidant status in serum and the level of AGEs, cross linking and browning of collagen in tail tendons and skin were investigated. The oxidative stress observed in diabetic rats was reduced significantly by curcumin administration. Nonenzymic antioxidants such as vitamin C, vitamin E, and glutathione were maintained at near normal values in curcumin-treated diabetic animals. Similarly, the accumulation of lipid peroxidation products in diabetic serum was reduced significantly by curcumin. Accelerated accumulation of AGE collagen in diabetic animals, as detected by ELISA, was prevented by curcumin. Extensive cross-linking of collagen in the tail tendon and skin of diabetic animals was also prevented to a greater extent by curcumin treatment. A correlation between the level of AGEs and collagen cross-linking was noted, suggesting the involvement of advanced glycation in cross-linking. It was also noted that the preventive effect of curcumin on the advanced glycation and cross linking of collagen was more pronounced than its therapeutic effect. However, the Maillard reaction fluorescence in both tail and skin collagen remained unaltered by curcumin. This study confirms the significance of free radicals in the accumulation of AGEs and cross-linking of collagen in diabetes. It supports curcumin administration for the prevention of AGE-induced complications of diabetes mellitus. PMID- 9973182 TI - Effect of flupirtine on cell death of human umbilical vein endothelial cells induced by reactive oxygen species. AB - Flupirtine (KATADOLON), known as a nonopiate centrally acting analgesic drug, was tested as to its potential to prevent apoptosis of human endothelial cells induced by reactive oxygen species (ROS). It was found that Flupirtine displayed no effect on viability and cell proliferation of human umbilical vein endothelial cells (HUVEC) up to a concentration of 10 microg/mL. Apoptosis, induced by ROS and generated by hypoxanthine/xanthine oxidase (EC 1.1.3.22) (HX/XOD) or t-butyl hydroperoxide, was reduced after preincubation with Flupirtine for 3 hr by 35% and 41%, respectively. The maximal cytoprotective effect against apoptosis was observed at a drug concentration of 1 to 3 microg/mL. Flow cytometric studies revealed that Flupirtine was able to decrease the number of necrotic cells as well as of apoptotic cells. Neither the simultaneous administration of Flupirtine with the apoptosis-inducing agent nor the preincubation of HUVEC with Flupirtine influenced the increase in the intracellular Ca2+ concentration [Ca2+]i caused by the production of ROS. PMID- 9973183 TI - Processing of adenosine receptor agonists in rat and human whole blood. AB - A stability study of adenosine receptor agonists in rat and human whole blood was performed. The compounds were incubated at 37 degrees in fresh blood, and aliquots of the incubation mixture were hemolyzed at regular time intervals and analyzed with HPLC. N6-cyclopentyladenosine (CPA) and N6-cyclobutyladenosine (CBA) were degraded, whereas N6-cyclohexyladenosine, N6-cycloheptyladenosine and N6-sulfophenyladenosine were not. 2-Chloroadenosine had a half-life very similar to that of CPA. However, the 2'-, 3'-, and 5'-deoxyribose derivatives of CPA remained intact. The nucleoside transport inhibitor nitrobenzylthioinosine attenuated CBA and CPA metabolism in rat blood as did the inhibitor of adenosine deaminase erythro-9-(2-hydroxy-3-nonyl)adenine, albeit at relatively high concentrations. Complete blockade of CBA and CPA degradation was achieved by a preincubation of rat and human blood with the adenosine kinase (AK) inhibitor 5' amino-5'-deoxyadenosine. We conclude that the two adenosine analogues are metabolized by AK both in rat and in human whole blood. PMID- 9973184 TI - Mitochondrial effects of L-ropivacaine, a new local anesthetic. AB - The effects of the local anesthetics ropivacaine and bupivacaine were investigated on isolated rat liver mitochondria. The efficiency of oxidative phosphorylation was evaluated by measuring the rates of respiration and ATP synthesis and the magnitude of the transmembrane electrical potential (deltapsi). Bupivacaine did not alter the ADP-stimulated respiration but strongly affected the resting respiration, which was more than doubled at 0.6 mM. In addition, it decreased the transmembrane electrical potential, and the ATP synthesis rate (deltapsi was less than 100 mV at 0.6 mM). Ropivacaine did not alter the ADP stimulated respiration, and the resting respiration seemed to be substantially unaffected up to 1.2 mM; a slight increase was observed at 1.8 and 2.4 mM. The transmembrane potential was decreased by anesthetic concentrations higher than 1.2 mM and ATP synthesis was consequently affected. The findings suggest that ropivacaine is less toxic than bupivacaine, in rat liver mitochondria. PMID- 9973185 TI - Incorporation of exogenous precursors into neutral lipids and phospholipids in rat hepatocytes: effect of ethanol in vitro. AB - We studied the incorporation of different radioactively labeled exogenous substrates into the lipids of rat hepatocytes previously incubated with ethanol. Glycerol, oleate, and serine were all incorporated into neutral lipids to a significantly greater degree in the presence of ethanol, the increase in radioactivity in the triacylglycerol fraction being quite substantial. A similar ethanol-induced increase was found in the incorporation of these substrates into the various phospholipids. This lipogenic activity did not occur when the metabolism of ethanol was blocked by 4-methylpyrazole, an inhibitor of hepatic ADH (alcohol:NAD+ oxidoreductase, EC 1.1.1.1) activity, thus demonstrating that one of the initial effects of ethanol on lipid biosynthesis was mediated by some products of its metabolism in the liver. The only alteration that persisted in the presence of 4-methylpyrazole was an inhibitory effect on the esterification of free cholesterol from oleate, suggesting that ethanol specifically inhibits hepatic ACAT (acyl CoA:cholesterol O-acyltransferase, EC 2.3.1.26) activity. PMID- 9973186 TI - Neuroprotective activities of carvedilol and a hydroxylated derivative: role of membrane biophysical interactions. AB - Carvedilol is a vasodilating beta-blocker and antioxidant approved for treatment of mild to moderate hypertension, angina, and congestive heart failure. SB 211475 (4-[2-hydroxyl-3-[[2-(2-methoxyphenoxy)ethyl]amino]propoxyl]-9H-++ +carbazol-3 ol), a hydroxylated carvedilol analogue, is an even more potent antioxidant in several assay systems. Carvedilol also has neuroprotective capacity with modulatory actions at N-methyl-D-aspartate (NMDA) receptors and Na+ channels. In the present study, we demonstrated that in cultured rat cerebellar neurons, SB 211475 has 28-fold greater antioxidant activity than carvedilol, but is 2- to 6 fold less potent, respectively, at inhibiting neurotoxic activities at Na+ channels and at NMDA receptor channels. To determine a biophysical rationale for these differential activities, small angle x-ray scattering data were obtained from model lipid and brain membrane bilayers containing either carvedilol, SB 211475, or dihydropyridine calcium channel blockers. Electron density profiles revealed that the location of SB 211475 was restricted to the glycerol backbone/hydrocarbon interface and significantly reduced membrane width by 5%, whereas the time-averaged location for carvedilol and flunarizine also extended to the hydrated surface of the bilayer. Comparison of carvedilol with several dihydropyridines showed a correlation between high ClogP values (lipophilicity), Na+ channel inhibitory potency, and bilayer localization. The antioxidant activity of SB 211475 could be explained by restricted intercalation into the glycerol phosphate/hydrocarbon interface, creating an increase in volume associated with the phospholipid acyl chains, which would then become resistant to lipid peroxidation. Differential channel modulation may also be explained by these membrane structural results, which indicate that carvedilol and the less spatially restricted dihydropyridine molecules are more likely to inhibit transmembrane receptor channels. PMID- 9973187 TI - Methoxyresorufin: an inappropriate substrate for CYP1A2 in the mouse. AB - Hepatic microsomes derived from Cypla2(-/-) knockout (KO) and parental strains of mice, C57BL/6N and 129Sv, were used to examine the specificity of methoxyresorufin and acetanilide as substrates for CYP1A2 activity. In addition, animals from each group were exposed to CYP1-inducing compounds. As expected, microsomes from untreated 1a2 KO mice did not have immunodetectable CYP1A2 protein; however, methoxyresorufin-O-demethylase (MROD, 25.5+/-6.1 pmol/min/mg protein) and acetanilide-4-hydroxylation (ACOH, 0.64+/-0.04 nmol/min/mg protein) activities were still present. Furthermore, induction of ethoxyresorufin-O deethylase (EROD) by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in 1a2 KO mice was accompanied by a greater than 70-fold increase in MROD activity. In contrast, ACOH was only induced 2-fold by TCDD. As with 1a2 KO mice, the parental strains exposed to TCDD or 2,3,4,7,8-pentachlorodibenzofuran (4-PeCDF) showed substantial EROD and MROD induction, whereas ACOH activity was induced to a lesser degree. PCB153 (2,2',4,4',5,5'-hexachlorobiphenyl) resulted in low levels of both EROD and MROD induction. Results indicate that both substrates are subject to metabolism by non-CYP1A2 sources, and the apparent contribution of CYP1A1 activity to methoxyresorufin metabolism makes MROD unsuitable for differentiating CYP1A1 and CYP1A2 activities in the mouse. PMID- 9973188 TI - Effects of antirheumatic drugs on adhesiveness of endothelial cells and neutrophils. AB - Because disease-modifying antirheumatic drugs might exert part of their effects on adhesion of polymorphonuclear neutrophils (PMN) to endothelial cells, this being the first step for PMN migration to inflammatory lesions, we evaluated such drug effects in vitro. Gold sodium thiomalate (GSTM) impaired the ability of interleukin 1beta (IL-1beta)-stimulated human umbilical vein endothelial cells (HUVEC) to express E-selectin and to bind PMN but had no effect on the expression of intercellular adhesion molecule 1 (ICAM-1) or on hyperadhesivity of N-formyl methionyl-leucyl-phenylalanine (fMLP)-stimulated PMN. Auranofin (AF) interacted with HUVEC and PMN adhesiveness but in opposite directions: this drug hampered IL 1beta-induced HUVEC hyperadhesiveness and expression of E-selectin and intercellular adhesion molecule 1, but augmented PMN adherence and CD18 expression. The net effect of auranofin was a reduction of cytokine-driven adhesiveness and enhancement of formylpeptide-induced adhesion. Salazopyrin did not affect HUVEC or PMN adhesiveness or E-selectin and intercellular adhesion molecule 1 expression. Thus, the gold-containing drugs modulated HUVEC and PMN adhesiveness by different mechanisms but ones involving surface adhesion molecules. PMID- 9973189 TI - Carboxymethyl benzylamide dextran blocks angiogenesis of MDA-MB435 breast carcinoma xenografted in fat pad and its lung metastases in nude mice. AB - We previously showed that carboxymethyl benzylamide dextran (CMDB7) prevents tumor growth and tumor angiogenesis by binding to angiogenic growth factors, thereby preventing them from reaching their receptors on tumor or stromal cells (Bagheri-Yarmand et al. Br. J. Cancer, 78: 111-118, 1998; Bagheri-Yarmand et al. Cell Growth Differ., 9: 497-504, 1998). In this study, CMDB7 inhibited neovessel formation within the fibroblast growth factor 2-enriched matrigel in mice, and its anticancer effect was then tested in a metastatic breast cancer model. Human MDA-MB435 cells were injected into the mammary fat pad of nude mice, and breast tumors developed within 1 week; all of the mice had lung metastases at 12 weeks. CMDB7 treatment (50, 150, or 300 s.c. or 300 i.v. mg/kg/week for 10 weeks) reduced the incidence of lung metastases to 12%. Histological analysis showed markedly less tumor neovascularization in the CMDB7-treated mice. Pulmonary metastasis incidence was strongly dependent on the intratumoral neoangiogenesis in primary tumors. PMID- 9973190 TI - Identification of a novel gene, MASL1, within an amplicon at 8p23.1 detected in malignant fibrous histiocytomas by comparative genomic hybridization. AB - We used comparative genomic hybridization to study malignant fibrous histiocytomas (MFHs) from 19 patients to detect changes in the copy number of DNA sequences, along entire chromosomes. Together with losses and gains in various chromosomal regions, distinct high-level amplifications were found at six loci (4q12-21, 8p21-pter, 8q24.1-qter, 9q12-13, 12p11.2-pter, and 15q11.2-15), suggesting that those regions may contain unknown (proto) oncogenes. We focused on the 8p amplicon, where detailed characterization allowed us to determine that the minimal common amplified region lay between markers D8S1819 and D8S550 at 8p23.1. A novel gene designated MASL1 (MFH-amplified sequences with leucine-rich tandem repeats 1) was isolated from within this narrowly defined region. Expression of the MASL1 gene was enhanced significantly in MFH tumors bearing the 8p amplicon. The primary structure of its deduced product revealed an ATP/GTP binding site, three leucine zipper domains, and a leucine-rich tandem repeat, all of which are important structural or functional elements for interactions among proteins related to the cell cycle. These features suggest that overexpression of MASL1 might well be oncogenic with respect to MFH. PMID- 9973191 TI - Functional evidence of novel tumor suppressor genes for cutaneous malignant melanoma. AB - Losses of heterozygosity involving chromosomes 9 and 10 are frequent events in the development and progression of cutaneous malignant melanoma. To investigate whether specifically deleted chromosomal regions encode tumor suppressor genes (TSGs), we introduced normal chromosome 10 into the tumorigenic human metastatic melanoma cell line UACC-903 by microcell fusion. In addition, two chromosome 9 derivatives that were microdeleted in the region of the p16INK4A/p15INK4B locus were transferred to determine whether an additional melanoma TSG or TSGs reside on chromosome 9p, as indicated by previous melanoma allele loss studies. In comparison to parental cells, microcell hybrids generated with chromosomes 9 (microdeleted) and 10 displayed reduced anchorage-independent growth in soft agar and markedly reduced tumorigenicity in athymic (nu/nu) mice. These data define a TSG or TSGs that function independently of p15/p16 on chromosome 9 and provide evidence for a TSG (or TSGs) on chromosome 10 that may be important in melanoma development. PMID- 9973192 TI - Chemoprevention of rat prostate carcinogenesis by 9-cis-retinoic acid. AB - A chemoprevention study was conducted to evaluate the activity of 9-cis-retinoic acid (9-cis-RA) as an inhibitor of prostate carcinogenesis in male Wistar Unilever (HsdCpb:Wu) rats. After pretreatment with a sequential regimen of cyproterone acetate (50 mg/kg/day for 21 days) and testosterone propionate (100 mg/kg/day for 3 days), groups of 40 rats received a single i.v. injection of N methyl-N-nitrosourea (MNU; 30 mg/kg body weight). Beginning 2 weeks after carcinogen administration, rats received chronic exposure to testosterone administered in s.c. implanted silastic capsules. The study was terminated at 13 months after MNU administration, and prostate cancer incidence was determined by histopathological evaluation of step sections of accessory sex glands. Continuous dietary administration of 9-cis-RA at 100 mg/kg diet or 50 mg/kg diet beginning 1 week before MNU administration reduced cancer incidence in the dorsolateral + anterior prostate from 65% in dietary controls to 18 and 20%, respectively (P < 0.001 for both comparisons). Similarly, these dose levels of 9-cis-RA reduced the incidence of cancer in all accessory sex glands from 79% in dietary controls to 48 and 33% (P < 0.01 for both comparisons), respectively. Chronic dietary administration of 9-cis-RA induced no gross or organ-specific toxicity in any animal and did not suppress group mean body weight gain. The potent anticarcinogenic activity of 9-cis-RA in the rat prostate, when considered with its apparent lack of toxicity in rodents, suggests that this and other ligands for the retinoid X receptor merit consideration for evaluation in clinical prostate cancer chemoprevention trials. PMID- 9973193 TI - Coexpression of estrogen receptor alpha and beta: poor prognostic factors in human breast cancer? AB - The cloning of a second estrogen receptor (ER), ER beta, has prompted a reevaluation of the role of ERs in breast cancer. The aim of this study was to determine the expression of both ER isoforms in normal (n = 23) and malignant (n = 60) human breast tissue by reverse transcription-PCR and correlate this information with known prognostic factors including tumor grade and node status. In normal breast tissue, expression of ER beta predominated, with 22% of samples exclusively expressing ER beta; this was not observed in any of the breast tumor samples investigated. Most breast tumors expressed ER alpha, either alone or in combination with ER beta. Interestingly, those tumors that coexpressed ER alpha and ER beta were node positive (P = 0.02; Fisher's exact test) and tended to be of higher grade. Because antiestrogens are agonists when signaling through the AP1 element, overexpression of ER beta in tumors expressing both ER subtypes may explain the failure of antiestrogen therapy in some breast cancer patients. Thus, ER beta may be a useful prognostic factor in patients with breast cancer. PMID- 9973194 TI - Estrogen receptor-beta messenger RNA expression in human breast tumor biopsies: relationship to steroid receptor status and regulation by progestins. AB - When the level of estrogen receptor (ER)-beta mRNA in tumors, determined by reverse transcription-PCR, was assessed according to either ER status or PR status alone, determined by ligand binding assays, the level of ER-beta mRNA was significantly lower in PR+ tumors compared with PR- tumors (P = 0.036), and no association with ER status was found. Subgroup analysis showed that ER-beta mRNA expression in ER+/PR+ breast tumors was significantly less than in ER+/PR- (P = 0.009), ER-/PR+ (P = 0.029), and ER-/PR- (P = 0.023) groups. Interestingly, the ER-beta mRNA expression was specifically decreased by progestin in T47D breast cancer cells. The data suggest the possibility that expression of ER-beta in human breast tumors is a marker of endocrine therapy responsiveness. PMID- 9973195 TI - BNIP3alpha: a human homolog of mitochondrial proapoptotic protein BNIP3. AB - Apoptosis is regulated by interaction of viral and cellular BCL-2 family antiapoptotic proteins with various pro-apoptotic proteins, several of which are also members of the BCL-2 family. Cellular protein BNIP3 is a BCL-2 family proapoptotic protein that interacts with viral antiapoptosis proteins such as adenoviruses E1B-19K and EBV-BHRF1 and cellular antiapoptosis proteins such as BCL-2 and BCL-xL. Database searches indicate that the human genome encodes an open reading frame for a protein, BNIP3alpha, that shares substantial homology with BNIP3. The BNIP3alpha open reading frame encodes a protein of 219 amino acids that contains a conserved BH3 domain and a COOH-terminal trans-membrane domain, characteristic of several BCL-2 family proapoptotic proteins. BNIP3alpha interacts with viral antiapoptosis protein E1B-19K and cellular antiapoptosis proteins BCL-2 and BCL-xL. Overexpression of BNIP3alpha in transfected cells results in apoptosis and suppresses the antiapoptosis activity of E1B-19K and BCL xL. Like BNIP3, BNIP3alpha seems to be predominantly localized in mitochondria. These results suggest that BNIP3alpha is a structural and functional homologue of BNIP3. BNIP3 and BNIP3alpha seem to be the first examples of homologues among the various human proapoptotic proteins. Northern blot analysis reveals that BNIP3alpha is expressed ubiquitously in most human tissues. In contrast, BNIP3 is expressed well in several human tissues and less abundantly in certain tissues such as placenta and lung. These results suggest that although BNIP3 and BNIP3alpha may promote apoptosis simultaneously in most human tissues, BNIP3alpha may play a more universal role. PMID- 9973196 TI - The human MLH1 cDNA complements DNA mismatch repair defects in Mlh1-deficient mouse embryonic fibroblasts. AB - The DNA mismatch repair gene hMLH1 is reported to function in mutation avoidance, cell cycle checkpoint control, the cytotoxicity of various DNA-damaging agents, and transcription-coupled nucleotide excision repair. Formal proof of the involvement of hMLH1 in these processes requires single gene complementation. We have stably expressed hMLH1 from a transfected cDNA in Mlh1-deficient mouse embryonic fibroblasts. Expression of hMLH1 restored normal levels of mPMS2 protein, reduced spontaneous base substitution and microsatellite mutations, increased sensitivity to the toxic effects of 6-thioguanine (6-TG), and restored 6-TG-induced cell cycle arrest. Our studies confirm that hMLH1 has an essential role in the maintenance of genomic stability and the potentiation of 6-TG cytotoxicity and provide a system for detailed structure/function analysis of the hMLH1 protein. PMID- 9973197 TI - Phosphoinositide 3-kinase activity is essential for all-trans-retinoic acid induced granulocytic differentiation of HL-60 cells. AB - Phosphoinositide 3-kinase (PI 3-K) activity increases in HL-60 cells that are induced to granulocytic differentiation by all-trans-retinoic acid. Immunochemical and immunocytochemical analyses by confocal microscopy also reveal an increase in the amount of the enzyme, which is particularly evident at the nuclear level. Inhibition of PI 3-K activity by nanomolar concentrations of wortmannin and of its expression by transfection with an antisense fragment of p85alpha prevented the differentiative process. The data obtained indicate that PI 3-K activity plays an essential role in promoting granulocytic differentiation. PMID- 9973198 TI - Independent regulation of growth and SMAD-mediated transcription by transforming growth factor beta in human melanoma cells. AB - Increased production of transforming growth factor beta (TGF-beta) coupled with resistance to the growth-inhibitory effects of TGF-beta is characteristic of several types of neoplasia including human melanoma. In select epithelial malignancies, lack of TGF-beta-induced growth inhibition is associated with disruptions of TGF-beta-dependent SMAD signaling and transcription. In contrast, the results of the present study indicate intact SMAD-dependent transcription in human melanoma cells, regardless of their proliferative response to exogenous TGF beta. Furthermore, in some melanoma cell lines constitutive SMAD-dependent transcription was observed, which was due in part to endogenous TGF-beta. These results establish that resistance of melanoma cells to TGF-beta-induced growth inhibition occurs independently of intact TGF-beta receptor/SMAD-mediated transcriptional regulation. They also suggest that melanoma-derived TGF-beta may exert autocrine effects on SMAD-sensitive target genes. PMID- 9973199 TI - Cloning of human telomerase catalytic subunit (hTERT) gene promoter and identification of proximal core promoter sequences essential for transcriptional activation in immortalized and cancer cells. AB - Telomerase activation is thought to be a critical step in cellular immortalization and carcinogenesis. Of the three major subunits comprising human telomerase, human telomerase catalytic subunit (hTERT) has been shown to be a rate-limiting determinant of the enzymatic activity of human telomerase. However, little is known concerning how expression of hTERT is regulated in human cells. To identify the regulatory elements controlling hTERT gene expression, approximately 3.5 kb of the 5'-flanking sequence of hTERT was cloned and characterized. The promoter of hTERT was GC rich and lacked both TATA and CAAT boxes. The CapSite Hunting method identified transcription start site 19 bp upstream of the first nucleotide of the published cDNA sequence. Transient expression assays revealed that transcription of hTERT was significantly activated in cancer cell lines but repressed in normal primary cells. Using the fibroblast lineage at various stages of transformation, we found that transcription occurred in strains that had overcome replicative senescence and expressed telomerase activity. Deletion analysis of hTERT promoter identified the 181-bp core promoter region upstream of the transcription start site. Gel shift analysis revealed two major factors binding to core promoter, an E box (CACGTG) binding factor and Sp1. Overexpression of c-Myc resulted in a significant increase in transcriptional activity of the core promoter. These findings suggest that hTERT expression is strictly regulated at the transcription machinery, and that the proximal core promoter containing an E box and Sp1 sites is required for transactivation of hTERT. PMID- 9973200 TI - Identification of functional elements of p18INK4C essential for binding and inhibition of cyclin-dependent kinase (CDK) 4 and CDK6. AB - Members of the INK4 family of cyclin-dependent kinase (CDK) inhibitors specifically bind and inhibit the G1-specific CDK molecules CDK4 and CDK6. One of the INK4 molecules, p16, is also known as multiple tumor suppressor and has been found to be mutated or deleted in various tumors and cell lines. We have previously identified p18 as a member of the INK4 family. To determine the molecular basis for the inhibitory function of p18, we introduced 11 missense mutations of conserved residues that were identified in p16 of cancer cell lines into p18. The effects of these mutations on the ability of p18 to bind and inhibit CDK4 and CDK6 or to inhibit cell growth were determined. Our results indicate that the third ankyrin repeat and the NH2-terminal portion of the fourth repeat constitute the essential element necessary for the ability of p18 to bind and inhibit CDK4 and CDK6. Apart from this core interaction element, p18 seems to use additional, distinct residues to differentially bind and inhibit CDK4 and CDK6, accounting for the known penchant of p18 to preferentially interact with CDK6. PMID- 9973201 TI - Transcription of the bone sialoprotein gene is stimulated by v-Src acting through an inverted CCAAT box. AB - Bone sialoprotein (BSP) is an early marker of differentiated osteoblasts that has been implicated in the nucleation of hydroxyapatite crystal formation during de novo bone formation. Although essentially specific to mineralizing connective tissues, BSP is also expressed ectopically by carcinomas that exhibit microcalcification and which metastasize to bone with high frequency. However, it is not known how BSP is regulated in transformed cells. Because the v-src oncogene induces expression of a number of genes that are involved in tumor growth and metastasis, including osteopontin, we have studied the effects of v Src on transcription of the BSP gene. Transfection of mouse src-/- cells with a v src expression vector increased the transcriptional activity of rat BSP promoter/luciferase chimeric constructs approximately 5-fold. Deletion analysis revealed that the v-Src activity was targeted to an inverted CCAAT box located immediately upstream from an inverted TATA box in the BSP promoter. Although mutation of the CCAAT box diminished the basal transcription activity of the BSP promoter, the Src-induced stimulation was completely abolished. Gel mobility shift analysis identified four nuclear factors that bound to this region of the BSP promoter, two of which required an intact CCAAT sequence. Monoclonal antibodies identified nuclear factor-Y (NF-Y) as the principal nuclear factor that bound to the CCAAT box; the second factor (beta) showing strong binding only in short constructs containing the CCAAT sequence. Transcription analyses with a dominant negative NF-Y expression vector confirmed that NF-Y mediated the action of v-Src. These studies indicate that BSP gene expression in transformed cells can be up-regulated by Src kinase activity through a mechanism mediated by the NF Y transcription factor, which targets an inverted CCAAT box in the BSP gene promoter. PMID- 9973202 TI - Protein kinase D in small cell lung cancer cells: rapid activation through protein kinase C. AB - Protein kinase C (PKC) is implicated in the regulation of a variety of important functions in small cell lung cancer (SCLC) cell lines, but the downstream signaling targets stimulated by PKCs in these cells remain poorly characterized. Here we report that treatment of the SCLC cell lines H 69, H 345, and H 510 with phorbol-12,13-dibutyrate (PDB) led to a rapid and striking activation of protein kinase D (PKD), a novel serine/threonine protein kinase distinct from all PKC isoforms. PKD activation induced by PDB in these SCLC cell lines was completely abrogated by treatment of the cells with the PKC inhibitor GF 109203X (GF I) at concentrations (0.5-2.5 microM) that did not inhibit PKD activity when added directly to the in vitro kinase assays. Treatment with the biologically active phorbol ester 12-O-tetradecanoylphorbol-13-acetate or with membrane-permeable diacylglycerols also stimulated PKD activation, which was also completely prevented by prior exposure of the cells to GF I. The PKC inhibitors Ro 31-8220 and Go 7874 also blocked PKD activation in response to PDB. Addition of the autocrine growth factor bombesin to cultures of H 345 cells induced significant PKD activation that also was prevented by GF I. Our results demonstrate, for the first time, the existence of a PKC/PKD pathway in SCLC cells and raise the possibility that PKD may be an important mediator of some of the biological responses elicited by PKC activation in SCLC cells. PMID- 9973203 TI - Cancer chemopreventive activity mediated by 4'-bromoflavone, a potent inducer of phase II detoxification enzymes. AB - Induction of phase II enzymes is an important mechanism of chemoprevention. In our search for novel cancer chemopreventive agents, 4'-bromoflavone (4'BF) was found to significantly induce quinone reductase (QR) activity in cultured murine hepatoma 1c1c7 cells (concentration to double activity: 10 nM) and effectively induce the alpha- and mu-isoforms of glutathione S-transferase in cultured H4IIE rat hepatoma cells with no observed toxicity. In short-term dietary studies, 4'BF was also shown to increase QR activity and glutathione levels in rat liver, mammary gland, colon, stomach, and lung in a dose-dependent manner. Induction mediated by 4'BF was bifunctional (induction of both phase I and phase II enzymes) and regulated at the transcriptional level, as revealed by transient transfection studies with plasmid constructs (pDTD-1097CAT, XRE-CAT, and ARE-CAT) and reverse transcription-PCR-based analysis of QR mRNA. In studies conducted with female Sprague Dawley rats, the effects of 4'BF on the relative induction levels of phase I and phase II enzyme activities were investigated in liver and mammary gland. Treatment with 4'BF and 7,12-dimethylbenz[a]anthracene (DMBA) or 4'BF alone did not significantly alter DMBA-induced cytochrome P4501A1 activity (phase I enzyme), but it significantly increased QR activity (phase II enzyme), compared with the DMBA treatment group. In addition, 4'BF was found to be a potent inhibitor of cytochrome P4501A1-mediated ethoxyresorufin-O-deethylase activity, with an IC50 of 0.86 microM. Furthermore, in studies conducted with cultured HepG2 or MCF-7 cells, 4'BF significantly reduced the covalent binding of metabolically activated benzo[a]pyrene to cellular DNA. On the basis of these results, a full-term cancer chemoprevention study was conducted with DMBA-treated female Sprague Dawley rats. Dietary administration of 4'BF (2000 and 4000 mg per kg of diet, from 1 week before to 1 week after DMBA) significantly inhibited the incidence and multiplicity of mammary tumors and greatly increased tumor latency. In summary, 4'BF can be viewed as a relatively simple, readily available, inexpensive compound that is a highly effective cancer chemopreventive agent. The full mechanism of action remains to be defined, but enhancement of detoxification pathways appears to be important. PMID- 9973204 TI - Polymorphic expression of the glutathione S-transferase P1 gene and its susceptibility to Barrett's esophagus and esophageal carcinoma. AB - Factors determining individual susceptibility to esophageal cancer or premalignant Barrett's epithelium are still largely unclear. An imbalance between phase I drug metabolism [e.g., cytochrome P450 (CYP)] and phase II detoxification [e.g., glutathione S-transferase (GST)] may contribute to the development of these diseases. Polymorphic variants in the CYP1A1 gene were described leading to increased levels of bioactive compounds, whereas polymorphisms in GST genes often resulted in impaired detoxification. We studied the frequencies of polymorphic variants in CYP1A1, GSTP1, GSTT1, and GSTM1 genes in 98 patients with Barrett's epithelium and 34 patients with esophageal cancer. The results were compared with those obtained from 247 healthy blood donors. DNA was extracted, and PCR-RFLP methods were used to detect genetic polymorphisms. Chi2 analysis, Spearman rank correlation, and Wilcoxon rank sum tests were used for statistical evaluation. Polymorphisms in CYP1A1, GSTM1, and GSTT1 occurred at an equal frequency in patients and controls. Occurrence of the polymorphic GSTP1b variant in the GSTP1 gene resulted in a significantly lower GST enzyme activity (P < 0.05), and GSTP1b was found significantly more often in patients with Barrett's epithelium (70%; P < 0.001) and patients with esophageal adenocarcinoma (76%; P = 0.005), as compared to healthy blood donors (41%). In conclusion, presence of the GSTP1b allele leads to lower GST enzyme activity levels and, consequently, impaired detoxification. This most important esophageal GST isoform may, therefore, contribute to the development of Barrett's epithelium and adenocarcinoma. PMID- 9973205 TI - Quantitation of urinary metabolites of a tobacco-specific lung carcinogen after smoking cessation. AB - We quantified urinary levels of two metabolites of the tobacco-specific lung carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) in people who had stopped smoking: 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) and its O glucuronide, 4-[(methylnitrosamino)-1-(3-pyridyl)but-1-yl]-beta-O-D glucosiduronic acid (NNAL-Gluc). Twenty-seven people completed the study. Thirteen used the nicotine patch starting at the quit date, whereas the others used no patch. Two 24-h urine samples were collected on 2 consecutive days before smoking cessation; blood was also obtained. Beginning at their quit date, subjects provided 24-h urine samples on days 7, 21, 42, 70, 98, and 126, and some subjects also provided samples at later times. The urine was analyzed for NNAL, NNAL-Gluc, nicotine plus nicotine-N-glucuronide, and cotinine plus cotinine-N glucuronide. Some blood samples were also analyzed for NNAL. The decline of urinary NNAL and NNAL-Gluc after smoking cessation was much slower than expected. This was clearly demonstrated by comparison with cotinine and nicotine levels in urine. One week after smoking cessation, 34.5% of baseline NNAL plus NNAL-Gluc was detected in urine, whereas the corresponding values for cotinine and nicotine were 1.1 and 0.5%, respectively. Even 6 weeks after cessation, 7.6% of the original levels of NNAL plus NNAL-Gluc remained. In some subjects, NNAL plus NNAL Gluc were detected 281 days after cessation. The distribution half-life for NNAL and NNAL-Gluc was 3-4 days, whereas the elimination half-life was 40-45 days. Total body clearance of NNAL was estimated to be 61.4 +/- 35.4 ml/min, and volume of distribution in the beta-phase was estimated to be 3800 +/- 2100 liters, indicating substantial distribution into the tissues. Parallel studies in rats treated chronically or acutely with NNK in the drinking water support the conclusion that NNAL has a large volume of distribution. There was no effect of the nicotine patch on levels of NNAL plus NNAL-Gluc, indicating that NNK is not formed endogenously from nicotine. The results of this study demonstrate that NNAL and NNAL-Gluc are slowly cleared from the body after smoking cessation, indicating the presence of a high-affinity compartment where NNK, NNAL, and/or NNAL-Gluc are retained or sequestered and slowly released. PMID- 9973206 TI - Chemopreventive effect of curcumin, a naturally occurring anti-inflammatory agent, during the promotion/progression stages of colon cancer. AB - Curcumin, derived from the rhizome of Curcuma longa L. and having both antioxidant and anti-inflammatory properties, inhibits chemically induced carcinogenesis in the skin, forestomach, and colon when it is administered during initiation and/or postinitiation stages. This study was designed to investigate the chemopreventive action of curcumin when it is administered (late in the premalignant stage) during the promotion/progression stage of colon carcinogenesis in male F344 rats. We also studied the modulating effect of this agent on apoptosis in the tumors. At 5 weeks of age, groups of male F344 rats were fed a control diet containing no curcumin and an experimental AIN-76A diet with 0.2% synthetically derived curcumin (purity, 99.9%). At 7 and 8 weeks of age, rats intended for carcinogen treatment were given s.c. injections of azoxymethane (AOM) at a dose rate of 15 mg/kg body weight per week. Animals destined for the promotion/progression study received the AIN-76A control diet for 14 weeks after the second AOM treatment and were then switched to diets containing 0.2 and 0.6% curcumin. Premalignant lesions in the colon would have developed by week 14 following AOM treatment. They continued to receive their respective diets until 52 weeks after carcinogen treatment and were then sacrificed. The results confirmed our earlier study in that administration of 0.2% curcumin during both the initiation and postinitiation periods significantly inhibited colon tumorigenesis. In addition, administration of 0.2% and of 0.6% of the synthetic curcumin in the diet during the promotion/progression stage significantly suppressed the incidence and multiplicity of noninvasive adenocarcinomas and also strongly inhibited the multiplicity of invasive adenocarcinomas of the colon. The inhibition of adenocarcinomas of the colon was, in fact, dose dependent. Administration of curcumin to the rats during the initiation and postinitiation stages and throughout the promotion/progression stage increased apoptosis in the colon tumors as compared to colon tumors in the groups receiving AOM and the control diet. Thus, chemopreventive activity of curcumin is observed when it is administered prior to, during, and after carcinogen treatment as well as when it is given only during the promotion/progression phase (starting late in premalignant stage) of colon carcinogenesis. PMID- 9973207 TI - Manganese superoxide dismutase (MnSOD) genetic polymorphisms, dietary antioxidants, and risk of breast cancer. AB - Oxidative stress, resulting from the imbalance between prooxidant and antioxidant states, damages DNA, proteins, cell membranes, and mitochondria and seems to play a role in human breast carcinogenesis. Dietary sources of antioxidants (chemical) and endogenous antioxidants (enzymatic), including the polymorphic manganese superoxide dismutase (MnSOD), can act to reduce the load of oxidative stress. We hypothesized that the valine-to-alanine substitution that seems to alter transport of the enzyme into the mitochondrion, changing its efficacy in fighting oxidative stress, was associated with breast cancer risk and that a diet rich in sources of antioxidants could ameliorate the effects on risk. Data were collected in a case-control study of diet and breast cancer in western New York from 1986 to 1991. Caucasian women with incident, primary, histologically confirmed breast cancer were frequency-matched on age and county of residence to community controls. Blood specimens were collected and processed from a subset of participants in the study (266 cases and 295 controls). Using a RFLP that distinguishes a valine (V) to alanine (A) change in the -9 position in the signal sequence of the protein for MnSOD, we characterized MnSOD genotypes in relation to breast cancer risk. We also evaluated the effect of the polymorphism on risk among low and high consumers of fruits and vegetables. Premenopausal women who were homozygous for the A allele had a 4-fold increase in breast cancer risk in comparison to those with 1 or 2 V alleles (odds ratio, 4.3; 95% confidence interval, 1.7-10.8). Risk was most pronounced among women below the median consumption of fruits and vegetables and of dietary ascorbic acid and alpha tocopherol, with little increased risk for those with diets rich in these foods. Relationships were weaker among postmenopausal women, although the MnSOD AA genotype was associated with an almost 2-fold increase in risk (odds ratio, 1.8; confidence interval, 0.9-3.6). No appreciable modification of risk by diet was detected for these older women. These data support the hypothesis that MnSOD and oxidative stress play a significant role in breast cancer risk, particularly in premenopausal women. The finding that risk was greatest among women who consumed lower amounts of dietary antioxidants and was minimal among high consumers indicates that a diet rich in sources of antioxidants may minimize the deleterious effects of the MnSOD polymorphism, thereby supporting public health recommendations for the consumption of diets rich in fruits and vegetables as a preventive measure against cancer. PMID- 9973208 TI - Isoform-specific induction of a human aldo-keto reductase by polycyclic aromatic hydrocarbons (PAHs), electrophiles, and oxidative stress: implications for the alternative pathway of PAH activation catalyzed by human dihydrodiol dehydrogenase. AB - Human dihydrodiol dehydrogenase (DD) isoforms are aldo-keto reductases (AKRs) that activate polycyclic aromatic hydrocarbons (PAHs) by oxidizing trans dihydrodiol proximate carcinogens to reactive and redox-active ortho-quinones. Of these, human AKR1C1 (DD1) and AKR1C2 (DD2) oxidize trans-7,8-dihydroxy-7,8 dihydrobenzo[a]pyrene to the cytotoxic and genotoxic metabolite benzo[a]pyrene 7,8-dione (BPQ) with the highest catalytic efficiency. Exposure of HepG2 cells to a panel of inducers revealed that mRNA encoding one or more human AKR1C member(s) was induced (3- to 10-fold) by benzo[a]pyrene and other polycyclic aromatic compounds (bi-functional inducers), electrophilic Michael acceptors and phenolic antioxidants (monofunctional inducers), and reactive oxygen species (ROS). The induction of AKR1C mRNA by bifunctional inducers was delayed with respect to the induction of CYP1A1 mRNA, and AKR1C mRNA was not induced by the nonmetabolizable aryl hydrocarbon receptor ligand 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). These data suggest that, in contrast to the CYPs, induction of AKR1C member(s) by PAHs and other bifunctional inducers is mediated indirectly via an antioxidant response element rather than a xenobiotic response element. Immunoblot and enzymatic assays confirmed that the increases in AKR1C mRNA were faithfully translated into functional AKR1C protein(s). The increased DD activity in HepG2 lysates was inhibited only by high concentrations of ursodeoxycholate, which suggested that AKR1C2 (DD2, bile-acid-binding protein) was not the isoform induced. RNase protection assays identified AKR1C1 (DD1) mRNA as the transcript which was up-regulated by mono- and bi-functional inducers and ROS in both human hepatoma (HepG2) and colon carcinoma (HT29) cells. BPQ, the electrophilic and redox-cycling product of the AKR1C1 reaction, also induced AKR1C1 expression. Thus, BPQ formation by AKR1C1 results in both a chemical (redox-cycling) and a genetic (AKR1C1 induction) amplification of ROS in PAH-exposed cells. Because ROS have been implicated in both tumor initiation and tumor promotion, the amplification of ROS by this pathway may play a significant role in PAH carcinogenesis. PMID- 9973209 TI - 2-[C-11]thymidine imaging of malignant brain tumors. AB - Malignant brain tumors pose diagnostic and therapeutic problems. Despite the advent of new brain imaging modalities, including magnetic resonance imaging (MRI) and [F-18]fluorodeoxyglucose (FDG) positron emission tomography (PET), determination of tumor viability and response to treatment is often difficult. Blood-brain barrier disruption can be caused by tumor or nonspecific reactions to treatment, making MRI interpretation ambiguous. The high metabolic background of the normal brain and its regional variability makes it difficult to identify small or less active tumors by FDG imaging of cellular energetics. We have investigated 2-[C-11]thymidine (dThd) and PET to image the rate of brain tumor cellular proliferation. A series of 13 patients underwent closely spaced dThd PET, FDG PET, and MRI procedures, and the image results were compared by standardized visual analysis. The resulting dThd scans were qualitatively different from the other two scans in approximately 50% of the cases, which suggests that dThd provided information distinct from FDG PET and MRI. In two cases, recurrent tumor was more apparent on the dThd study than on FDG; in two other patients, tumor dThd uptake was less than FDG uptake, and these patients had slower tumor progression than the three patients with both high dThd and FDG uptake. To better characterize tumor proliferation, kinetic modeling was applied to dynamic dThd PET uptake data and metabolite-analyzed blood data in a subset of patients. Kinetic analysis was able to remove the confounding influence of [C 11]CO2, the principal labeled metabolite of 2-[C-11]dThd, and to estimate the flux of dThd incorporation into DNA. Sequential, same-day [C-11]CO2 and [C 11]dThd imaging demonstrated the ability of kinetic analysis to model both dThd and CO2 simultaneously. Images of dThd flux obtained using the model along with the mixture analysis method for pixel-by-pixel parametric imaging significantly enhanced the contrast of tumor compared with normal brain. Comparison of model estimates of dThd transport versus dThd flux was able to discern increased dThd uptake simply on the basis of blood-brain barrier disruption retention on the basis of increased cellular proliferation. This preliminary study demonstrates the potential for imaging brain tumor cellular proliferation to provide unique information for guiding patient treatment. PMID- 9973210 TI - A flavonoid antioxidant, silymarin, affords exceptionally high protection against tumor promotion in the SENCAR mouse skin tumorigenesis model. AB - In cancer chemoprevention studies, the identification of better antitumor promoting agents is highly desired because they may have a wider applicability against the development of clinical cancers. Both epidemiological and animal studies have suggested that microchemicals present in the diet and several herbs and plants with diversified pharmacological properties are useful agents for the prevention of a wide variety of human cancers. Silymarin, a flavonoid isolated from milk thistle, is used clinically in Europe and Asia as an antihepatotoxic agent, largely due to its strong antioxidant activity. Because most antioxidants afford protection against tumor promotion, in this study, we assessed the protective effect of silymarin on tumor promotion in the SENCAR mouse skin tumorigenesis model. Application of silymarin prior to each 12-O tetradecanoylphorbol 13-acetate (TPA) application resulted in a highly significant protection against tumor promotion in 7,12-dimethylbenz(a)anthracene initiated mouse skin. The protective effect of silymarin was evident in terms of reduction in tumor incidence (25, 40, and 75% protection, P < 0.001, X2 test), tumor multiplicity (76, 84, and 97% protection, P < 0.001, Wilcoxon rank sum test), and tumor volume (76, 94, and 96% protection, P < 0.001, Student's t test) at the doses of 3, 6, and 12 mg per application, respectively. To dissect out the stage specificity of silymarin against tumor promotion, we next assessed its effect against both stage I and stage II of tumor promotion. Application of silymarin prior to that of TPA in stage I or mezerein in stage II tumor promotion in dimethylbenz(a)anthracene-initiated SENCAR mouse skin resulted in an exceptionally high protective effect during stage I tumor promotion, showing 74% protection against tumor incidence (P < 0.001, X2 test), 92% protection against tumor multiplicity (P < 0.001, Wilcoxon rank sum test), and 96% protection against tumor volume (P < 0.001, Student's t test). With regard to stage II tumor promotion, silymarin showed 26, 63, and 54% protection in tumor incidence, multiplicity, and volume, respectively. Similar effect of silymarin to that in anti-stage I studies, were also observed when applied during both stage I and stage II protocols. In other studies, silymarin significantly inhibited: (a) TPA induced skin edema, epidermal hyperplasia, and proliferating cell nuclear antigen positive cells; (b) DNA synthesis; and (c) epidermal lipid peroxidation, the early markers of TPA-caused changes that are associated with tumor promotion. Taken together, these results suggest that silymarin possesses exceptionally high protective effects against tumor promotion, primarily targeted against stage I tumors, and that the mechanism of such effects may involve inhibition of promoter induced edema, hyperplasia, proliferation index, and oxidant state. PMID- 9973211 TI - Stimulation of tumors to synthesize tumor necrosis factor-alpha in situ using 5,6 dimethylxanthenone-4-acetic acid: a novel approach to cancer therapy. AB - The selective induction of tumor vascular collapse represents an exciting approach to cancer treatment. However, clinical evaluation of tumor necrosis factor-alpha (TNF), an agent that accomplishes this goal, has been limited by systemic toxicity, and clinical approaches using bacterial components to induce TNF production have also been disappointing. Our laboratory has developed synthetic low molecular weight inducers of TNF, including 5,6-dimethylxanthenone 4-acetic acid (DMXAA), as an alternative strategy. DMXAA induces rapid vascular collapse in transplantable murine tumors and induces TNF synthesis in vitro in both murine and human systems. We show here that the extent of DMXAA-induced TNF synthesis is greater in tumors than that in the spleen, liver, or serum. As shown by in situ hybridization studies of the murine Colon 38 tumor, DMXAA induced tumor as well as host cells to express TNF mRNA. The distribution of cells containing TNF mRNA in tumor tissues after DMXAA administration contrasted significantly with that obtained after lipopolysaccharide (LPS) treatment, although splenic and hepatic tissues showed a similar distribution of TNF mRNA positive cells. In the Colon 38 tumor, the action of LPS was limited to host cells in the periphery of the vessels. DMXAA treatment induced 7-fold higher peak TNF levels in tumor than in serum. In contrast, LPS treatment induced 9-fold higher TNF levels in serum than in tumor. DMXAA induced 35-fold higher TNF activity in the Colon 38 tissue than did LPS. One ovarian, one squamous, and three melanoma human tumor xenografts implanted in athymic nude mice expressed TNF mRNA of human and murine origin in response to DMXAA, confirming that DMXAA can activate both host and tumor cells. The use of low molecular weight agents to induce TNF synthesis in situ in the tumor represents a novel approach to TNF mediated therapy of cancers. PMID- 9973212 TI - Effects of cationic porphyrins as G-quadruplex interactive agents in human tumor cells. AB - A series of cationic porphyrins has been identified as G-quadruplex interactive agents (QIAs) that stabilize telomeric G-quadruplex DNA and thereby inhibit human telomerase; 50% inhibition of telomerase activity was achieved in HeLa cell-free extract at porphyrin concentrations in the range < or = 50 microM. Cytotoxicity of the porphyrins in vitro was assessed in normal human cells (fibroblast and breast) and human tumor cells representing models selected for high telomerase activity and short telomeres (breast carcinoma, prostate, and lymphoma). In general, the cytotoxicity (EC50, effective concentration for 50% inhibition of cell proliferation) against normal and tumor cells was > 50 microM. The porphyrins were readily absorbed into tumor cell nuclei in culture. Inhibition of telomerase activity in MCF7 cells by subcytotoxic concentrations of TMPyP4 showed time and concentration dependence at 1-100 microM TMPyP4 over 15 days in culture (10 population doubling times). The inhibition of telomerase activity was paralleled by a cell growth arrest in G2-M. These results suggest that relevant biological effects of porphyrins can be achieved at concentrations that do not have general cytotoxic effects on cells. Moreover, the data support the concept that a rational, structure-based approach is possible to design novel telomere interactive agents with application to a selective and specific anticancer therapy. PMID- 9973213 TI - Eradication of rat malignant gliomas by retroviral-mediated, in vivo delivery of the interleukin 4 gene. AB - Overexpression of interleukin 4 (IL-4) can impair the tumorigenicity of glioma cells, but direct evidence of its antitumor efficacy after in vivo gene transfer into malignant gliomas has not been provided. To test this, we first injected into the brain of Sprague Dawley rats a 1:1 mixture of C6 rat glioblastoma cells and psi2.L4SN20 or E86.L4SN50 retroviral producer cells (RPCs), secreting 20 and 50 ng of IL-4/5 x 10(5) cells/48 h, respectively. Twenty-seven and 56% of rats receiving injections with these low- or medium-level IL-4 RPCs, respectively, survived tumor injection, whereas control rats died in about 1 month. E86.L4SN50 RPCs coinjected with 9L gliosarcoma cells into syngeneic Fischer 344 rats yielded similar results. A novel IL-4 RPC clone expressing higher levels of IL-4, E86.L4SN200, coinjected with 9L cells increased to 75% the fraction of long-term survivors and induced tumor regression in 50% of rats when injected into established 9L gliosarcomas. Cured rats developed an immunological memory because they rejected a challenge of wild-type 9L cells into the contralateral hemisphere. Magnetic resonance imaging was used to monitor 9L and C6 gliomas and gave direct evidence for tumor rejection in treated rats. Immunohistology showed inflammatory infiltrates in IL-4-treated tumors in which CD8+ T lymphocytes were more abundant, although CD4+ T lymphocytes, B lymphocytes, and macrophages were also present. Overall, these findings suggest that IL-4 gene transfer is a new, promising approach for treating malignant gliomas. PMID- 9973214 TI - Laulimalide and isolaulimalide, new paclitaxel-like microtubule-stabilizing agents. AB - A mechanism-based screening program aimed at the discovery of new antimicrotubule agents from natural products yielded laulimalide and isolaulimalide, two compounds with paclitaxel-like microtubule-stabilizing activity. Treatment of A 10 cells with laulimalide resulted in a dose-dependent reorganization of the cellular microtubule network and the formation of microtubule bundles and abnormal mitotic spindles. Coincident with the microtubule changes, these two compounds induced nuclear convolution and the formation of multiple micronuclei. Laulimalide is a potent inhibitor of cellular proliferation with IC50 values in the low nanomolar range, whereas isolaulimalide is much less potent with IC50 values in the low micromolar range. In contrast to paclitaxel, both laulimalide and isolaulimalide inhibited the proliferation of SKVLB-1 cells, a P-glycoprotein overexpressing multidrug-resistant cell line, suggesting that they are poor substrates for transport by P-glycoprotein. Incubation of MDA-MB-435 cells with laulimalide resulted in mitotic arrest and activation of the caspase cascade of proteolytic enzymes that accompany apoptotic cell death. Laulimalide stimulated tubulin polymerization and, although less potent than paclitaxel, it was more effective. Laulimalide-induced tubulin polymers resembled paclitaxel-induced polymers, although the laulimalide-induced polymers appeared notably longer. Laulimalide and isolaulimalide represent a new class of microtubule-stabilizing agents with activities that may provide therapeutic utility. PMID- 9973215 TI - Radioisotope concentrator gene therapy using the sodium/iodide symporter gene. AB - We demonstrate a novel method of concentrating radiation for tumor imaging or killing. The rat sodium/iodide symporter gene (rNIS) was cloned into a retroviral vector for transfer into cancer cells to mimic the iodide uptake of thyroid follicular cells. In vitro iodide transport shows that the symporter functions similarly in rNIS-transduced tumor cells and rat thyroid follicular cells. rNIS transduced and control nontransduced (NV) human A375 melanoma xenografts established in vivo in athymic nude mice were imaged using a gamma camera after i.p. injections of 123I. The rNIS-transduced human A375 melanoma tumors are visually distinguishable from and accumulate significantly more radionuclides than NV tumors. In vitro clonogenic assays confirm efficacy and clearly show that rNIS-transduced A375 human melanoma, BNL.1 ME murine transformed liver, CT26 murine colon carcinoma, and IGROV human ovarian carcinoma can be selectively killed by the induced accumulation of 131I. Thus, NIS-based gene therapy may have both diagnostic and therapeutic applications for cancer. PMID- 9973216 TI - Cytotoxicity and accumulation of ganciclovir triphosphate in bystander cells cocultured with herpes simplex virus type 1 thymidine kinase-expressing human glioblastoma cells. AB - The ability of herpes simplex virus type 1 thymidine kinase (HSV-TK)-expressing cells incubated with ganciclovir (GCV) to induce cytotoxicity in neighboring HSV TK-negative (bystander) cells has been well documented. Although it has been suggested that this bystander cell killing occurs through the transfer of phosphorylated GCV, there is little direct proof that bystander cells can accumulate GCV nucleotides. We have studied the ability of U251 human glioblastoma cells expressing HSV-TK (U251tk cells) to induce cytotoxicity in neighboring U251 bystander cells that lack the viral kinase (U251beta gal cells) and evaluated whether this bystander cell killing is mediated by GCV nucleotides. The cytotoxicity studies demonstrated that the ratio of HSV-TK-expressing cells:bystander cells was important in determining the sensitivity of both cell types to GCV. U251tk cells cocultured with an equal number of U251beta gal cells (a 50:50 ratio) exhibited a sensitivity to GCV similar to that observed in the absence of bystander cells, with >99.8% cell kill at 1 microm GCV. However, in cultures with 10% U251tk cells and 90% bystander cells (a 10:90 ratio), 1 microM GCV decreased the survival of U251tk cells by only 54%. Strong bystander cell killing was observed at both ratios. In a 50:50 coculture of U251tk and U251beta gal cells, the survival of bystander cells was decreased by >99.5% with 3 microM GCV, whereas 30 microM GCV was required to effect a similar decrease in bystander cell survival when 90% of the culture consisted of U251beta gal cells. To determine whether this bystander cell killing may be mediated by GCV nucleotides, we developed a technique to separate the two cell populations after coculture. A U251 bystander cell line was developed from the parental cell line by transfection with the cDNA coding for green fluorescent protein (U251gfp cells), which permitted the separation of U251gfp cells from nonfluorescing U251tk cells by flow cytometry with cell sorting. With this technique, bystander cells were isolated in a viable state with >97% purity within 1 h after harvest, permitting analysis of the nucleotide pools for the presence of phosphorylated GCV. The results demonstrated that significant levels of the triphosphate of GCV (GCVTP) accumulated in bystander cells within 4 h of coculture, and this accumulation was dependent upon the percentage of HSV-TK-expressing cells as well as the concentration of GCV and the length of incubation. The proportion of GCVTP in bystander cells was consistently 50-80% of that in HSV-TK-expressing cells in the 50:50 or 10:90 cocultures, suggesting a facile transfer of phosphorylated GCV. However, the actual amount of GCVTP was as much as 8-fold lower in both the U251tk and U251beta gal cells cocultured at a ratio of 10:90 compared to those cocultured at a ratio of 50:50, which is consistent with the lesser effect on cell survival. When U251tk and U251gfp cells were cultured with 1-beta-D arabinofuranosylthymine (araT), the 5'-triphosphate of araT accumulated in the bystander cells, demonstrating that the transfer of phosphorylated compounds between these cell types is not restricted to GCV nucleotides. However, the proportion of araT-5'-triphosphate in bystander cells compared to that in HSV-TK expressing cells was lower than that for GCVTP, and the amount was not sufficient to decrease survival in the bystander population. PMID- 9973217 TI - Induction of protective host immunity to carcinoembryonic antigen (CEA), a self antigen in CEA transgenic mice, by immunizing with a recombinant vaccinia-CEA virus. AB - Human carcinoembryonic antigen (CEA) is a well-characterized oncofetal glycoprotein whose overexpression by human carcinomas has been a target for cancer immunotherapy. Transgenic mice that express CEA as a self-antigen with a tissue distribution similar to that of humans have been developed. This study investigates: (a) the responsiveness of the CEA transgenic (CEA.Tg) mice to endogenous CEA or CEA administered as a whole protein in adjuvant; and (b) whether the presentation of CEA as a recombinant vaccinia virus could generate CEA-specific host immunity. By and large, the CEA.Tg mice were unresponsive to CEA, as shown by the lack of detectable CEA-specific serum antibodies and the inability to prime an in vitro splenic T-cell response to CEA. Furthermore, the administration of whole CEA protein in adjuvant to CEA.Tg mice failed to elicit either anti-CEA IgG titers or CEA-specific T-cell responses. Only weak anti-CEA IgM antibody titers were found in those mice. In contrast, CEA.Tg mice immunized with recombinant vaccinia virus expressing CEA generated relatively strong anti CEA IgG antibody titers and demonstrated evidence of immunoglobulin class switching. These mice also developed T(H)1-type CEA-specific CD4+ responses and CEA peptide-specific cytotoxicity. The ability to generate CEA-specific host immunity correlated with protection of the CEA.Tg mice against a challenge with CEA-expressing tumor cells. Protection against tumor growth was accomplished with no apparent immune response directed at CEA-positive normal tissue. The results demonstrate the ability to generate an effective antitumor immune response to a tumor self-antigen by immunization with a recombinant vaccinia virus. CEA.Tg mice should be an excellent experimental model to study the effects of more aggressive immunization schemes directed at established tumors with the possible development of accompanying autoimmune responses involving normal tissues. PMID- 9973218 TI - Reduced expression of the cell cycle inhibitor p27Kip1 in non-small cell lung carcinoma: a prognostic factor independent of Ras. AB - Levels of p27 have been found to have independent prognostic significance in a variety of tumors including breast, colon, prostate, ovary, and gastric carcinomas. We investigated p27 levels and determined ras mutational status in 136 non-small cell lung cancers. We found reduced levels of p27 in 86% of cases and showed a statistically significant inverse correlation between p27 levels and tumor grade. ras mutations were found exclusively in adenocarcinomas and showed no relationship to p27 levels. Clinical data on a subset of the patients studied indicated that all 16 patients who died of disease and 21 of 22 patients who relapsed had low p27 levels, whereas all patients with high p27 levels were alive at last follow up. These findings suggest that alteration in p27 levels plays an important role in lung tumor progression and that p27 levels may have independent prognostic significance in non-small cell lung cancer. PMID- 9973219 TI - N-(2-chloroethyl)-N-nitrosourea tethered to lexitropsin induces minor groove lesions at the p53 cDNA that are more cytotoxic than mutagenic. AB - Many different N-chloroethyl-N-nitrosourea (CENU) derivatives have been synthesized in an attempt to minimize carcinogenic activity while favoring antineoplastic activity. CENU derivatives linked to the dipeptide lexitropsin (lex) showed significant changes in groove- and sequence-selective DNA alkylation inducing thermolabile N3-alkyladenines (N3-Alkyl-As) at lex equilibrium binding sites. CENU-lex sequence specificity for DNA alkylation was determined using 32P end-labeled restriction fragments of the p53 cDNA. The adducted sites were converted into single-strand breaks by sequential heating at neutral pH and exposure to piperidine. To establish the mutagenic and lethal properties of CENU lex-specific lesions, a yeast expression vector harboring a human wild-type p53 cDNA was treated in vitro with CENU-lex and transfected into a yeast strain containing the ADE2 gene regulated by a p53-responsive promoter. p53 mutants were isolated from independent ade- transformants. The results revealed that: (a) CENU lex preferentially induces N3-Alkyl-A at specific lex equilibrium binding sites, the formations of which are strongly inhibited by distamycin; (b) reactivity toward Gs is still present, albeit to a lesser extent when compared to N-(2 chloroethyl)-N-cyclohexyl-N-nitrosourea and to CENU; (c) 91% of the 49 CENU-lex p53 mutations (45 of 49) were bp substitutions, 29 of which were GC-->AT transitions, mainly at 5' purine G sites; (d) all AT-targeted mutations but one were AT-->TA transversions; (e) the distribution of the CENU-lex mutations along the p53 cDNA was not random, with position 273 (codon 91), where only GC-->AT transitions were observed, being a real (n = 3, P < 0.0002) CENU-lex mutation hot spot; and (f) a shift in DNA alkylation sites between lesion spectra induced by CENU-lex and N-(2-chloroethyl-N-cyclohexyl-N-nitrosourea was associated with an increased lethality and a decreased mutagenicity, whereas no dramatic change in mutational specificity was observed. Hence, it is tempting to conclude that, in this experimental system, N3-Alkyl-A is more lethal than mutagenic, whereas O6 alkylguanine is a common premutational lesion formed at non-lex binding sites. These results suggest that CENU derivatives with virtually absolute specificity for A residues would make targeting of lethal, nonmutagenic lesions at A+T-rich regions possible, and this may represent a new strategy for the development of new chemotherapeutic agents with a higher therapeutic index. PMID- 9973220 TI - Bax is frequently compromised in Burkitt's lymphomas with irreversible resistance to Fas-induced apoptosis. AB - We have analyzed the Fas-mediated death pathway in a panel of 11 Epstein-Barr virus (EBV)-negative and 10 EBV-positive Burkitt's lymphoma (BL) cell lines. We show that the increased expression of Fas in EBV-positive cell lines is mediated via LMP-1. Four of the 21 BL cell lines are readily responsive to Fas-mediated cell death signals. Of the remaining 17 cell lines, 10 can be sensitized by up regulating Fas either via exogenous expression of LMP-1 or via treatment with CD40L. These same cell lines can also be sensitized by treatment with cycloheximide (CHX), which, however, does not result in up-regulation of Fas. Neither up-regulation of Fas, nor treatment with CHX, restore Fas sensitivity in seven BL cell lines. Further analyses indicated that 5 of the 7 cell lines (and none of the 14 responsive cell lines) were also compromised in the integrity/expression of the proapoptotic gene Bax. Thus, in most BL cell lines, the Fas pathway seems to be inhibited, although the mechanism of inhibition varies. The correlation between Bax mutation and irreversible (by CD40L or CHX) Fas resistance raises the possibility, for the first time, that Bax may play a critical function in Fas-mediated cell death in BL. PMID- 9973221 TI - Yeast proteins related to the p40/laminin receptor precursor are required for 20S ribosomal RNA processing and the maturation of 40S ribosomal subunits. AB - Numerous studies have linked the overexpression of the Mr 37,000 laminin receptor precursor (37-LRP) to tumor cell growth and proliferation. The role of this protein in carcinogenesis is generally considered in the context of its putative role as a precursor for the Mr 67,000 high-affinity laminin receptor. Recent studies have shown that 37-LRP, also termed p40, is a component of the small ribosomal subunit indicating that it may be a multifunctional protein. The p40/37 LRP protein is highly conserved phylogenetically, and closely related proteins have been identified in species as evolutionarily distant as humans and the yeast, Saccharomyces cerevisiae. Yeast homologues of p40/37-LRP are encoded by a duplicated pair of genes, RPS0A and RPS0B. The Rps0 proteins are essential components of the 40S ribosomal subunit. Previous results have shown that cells disrupted in either of the RPS0 genes have a reduction in growth rate and reduced amounts of 40S ribosomal subunits relative to wild-type cells. Here, we show that the Rps0 proteins are required for the processing of the 20S rRNA-precursor to mature 18S rRNA, a late step in the maturation of 40S ribosomal subunits. Immature subunits that are depleted of Rps0 protein that contain the 20S rRNA precursor are preferentially excluded from polysomes, which indicates that their activity in protein synthesis is dramatically reduced relative to mature 40S ribosomal subunits. These data demonstrate that the assembly of Rps0 proteins into immature 40S subunits and the subsequent processing of 20S rRNA represent critical steps in defining the translational capacity of yeast cells. If the function of these yeast proteins is representative of other members of the p40/37 LRP family of proteins, then the role of these proteins as key components of the protein synthetic machinery should also be considered as a basis for the linkage between the their overexpression and tumor cell growth and proliferation. PMID- 9973222 TI - Activation of neurotrophin-3 receptor TrkC induces apoptosis in medulloblastomas. AB - Elevated expression of the neurotrophin-3 (NT-3) receptor TrkC by childhood medulloblastomas is associated with favorable clinical outcome. Here, we provide evidence that TrkC is more than simply a passive marker of prognosis. We demonstrate that: (a) medulloblastomas undergo apoptosis in vitro when grown in the presence of NT-3; (b) overexpression of TrkC inhibits the growth of intracerebral xenografts of a medulloblastoma cell line in nude mice; and (c) trkC expression by individual tumor cells is highly correlated with apoptosis within primary medulloblastoma biopsy specimens. TrkC-mediated NT-3 signaling promotes apoptosis by activating multiple parallel signaling pathways and by inducing immediate-early gene expression of both c-jun and c-fos. Considered collectively, these results support the conclusion that the biological actions of TrkC activation affect medulloblastoma outcome by inhibiting tumor growth through the promotion of apoptosis. PMID- 9973223 TI - Expression of endothelin 1 and endothelin A receptor in ovarian carcinoma: evidence for an autocrine role in tumor growth. AB - In the present study, we have investigated the expression of endothelin 1 (ET-1) and the ET(A) receptor (ET(A)R) and ET(B) receptor (ET(B)R) in primary (n = 30) and metastatic (n = 8) ovarian carcinomas and their involvement in tumor growth. By reverse transcription-PCR and Northern blot analysis, we detected ET-1 mRNA in 90% of primary and 100% of metastatic ovarian carcinomas. ET-1 mRNA expression was significantly higher in tumors than in normal ovarian tissues (n = 12; P < 0.01). ET(A)R mRNA was also detected in 84% of the carcinomas examined, whereas ET(B)R mRNA was expressed in 50% of the tumors. The in vivo presence of mature ET 1 and ET(A)R was confirmed by immunohistochemistry, demonstrating a higher expression in primary and metastatic cells. Ten primary cultures of ovarian tumors secreted ET-1 and were positive for ET-1 and ET(A)R mRNA, whereas only 40% expressed ET(B)R mRNA. Radioligand binding studies showed that ET-1-producing cells also expressed functional ET(A)R, whereas no specific ET(B)R could be demonstrated. ET-1 stimulated dose-dependent [3H]thymidine incorporation and enhanced the mitogenic effect of epidermal growth factor. The ET(A)R-selective antagonist BQ 123 strongly inhibited ET-1-stimulated growth and substantially reduced the basal growth rate of unstimulated cells, whereas the ET(B)R-selective antagonist BQ 788 had no effect. In conclusion, the present data demonstrate a novel mechanism in the growth control of ovarian carcinoma in vivo mediated by the ET-1 autocrine loop that selectively occurs via the ET(A)R. PMID- 9973224 TI - Expression of vascular endothelial growth factor and its receptors in hematopoietic malignancies. AB - Vascular endothelial growth factor (VEGF) plays an important role in angiogenesis by acting as a potent inducer of vascular permeability as well as serving as a specific endothelial cell mitogen. The importance of angiogenic factors such as VEGF, although clearly established in solid tumors, has not been fully elucidated in human hematopoietic neoplasms. We examined the expression of mRNA and protein for VEGF in 12 human hematopoietic tumor cell lines, representing multiple lineages and diseases, including leukemia, lymphoma, and multiple myeloma. Our results revealed that VEGF message was expressed in these cells and that the corresponding protein was secreted into the extracellular environment. Five of the 12 cell lines were also found to express the Flt-1 receptor for VEGF at a moderate to strong level, suggesting an autocrine pathway. When human vascular endothelial cells were exposed to recombinant human VEGF, there was an increase in the mRNA for several hematopoietic growth factors including macrophage colony stimulating factor, granulocyte colony-stimulating factor and interleukin 6. Plasma cells in the bone marrow from patients diagnosed with multiple myeloma were found to express VEGF, whereas both the Flt-1 and KDR high affinity VEGF receptors were observed to be markedly elevated in the normal bone marrow myeloid and monocytic cells surrounding the tumor. These data raise the possibility that VEGF may play a role in the growth of hematopoietic neoplasms such as multiple myeloma through either a paracrine or an autocrine mechanism. PMID- 9973225 TI - Chemotherapy augments TRAIL-induced apoptosis in breast cell lines. AB - Expression and function of the TRAIL apoptotic pathway was investigated in normal and malignant breast epithelial cells. Glutathione-S-transferase (GST)-TRAIL extracellular domain fusion proteins were produced to analyze TRAIL-induced apoptosis. Only GST-TRAIL constructs containing regions homologous to the Fas self-association and ligand binding domains could induce apoptosis. GST-TRAIL induced significant (>90%) apoptosis in just one of eight normal and one of eight malignant breast cell lines. All other lines were relatively resistant to TRAIL induced apoptosis. Activating TRAIL receptors DR4 and DR5 were expressed in all normal and malignant breast cell lines. The inhibitory receptor TRID was highly expressed in one of four normal and two of seven malignant breast cell lines. DR4, DR5, or TRID expression did not correlate with sensitivity to TRAIL-induced apoptosis. Incubation of cell lines with doxorubicin or 5-fluorouracil significantly augmented TRAIL-induced apoptosis in most breast cell lines. By fractional inhibition analysis, the toxicity of the combination of TRAIL and doxorubicin or 5-fluorouracil was synergistic compared with either agent alone. In contrast, melphalan and paclitaxel augmented TRAIL-induced apoptosis in few cell lines, and methotrexate did not augment it in any cell line. Augmentation of TRAIL-induced apoptosis by doxorubicin or 5-fluorouracil was mediated through caspase activation. This was evidenced by the fact that chemotherapy agents that synergized with TRAIL (e.g., doxorubicin) themselves caused cleavage of caspase-3 and poly(ADP-ribose) polymerase (PARP), and their toxicity was blocked by the caspase inhibitor Z-Val-Ala-Asp(OMe)-CH2 (ZVAD-fmk). The combination of TRAIL and doxorubicin caused significantly greater caspase-3 and PARP cleavage, and the combined toxicity also was inhibited by ZVAD-fmk. In contrast, chemotherapy agents that did not augment TRAIL-induced apoptosis (e.g., methotrexate) caused minimal caspase-3 and PARP cleavage by themselves, and their toxicity was not inhibited by ZVAD-fmk. These drugs also did not increase caspase-3 or PARP cleavage when combined with TRAIL. In summary, few breast cell lines are sensitive to TRAIL-induced apoptosis, and no difference in sensitivity is found between normal and malignant cell lines. Treatment with chemotherapy provides an approach to sensitize breast cancer cells to TRAIL-induced apoptosis. PMID- 9973226 TI - Stimulation of breast cancer invasion and metastasis by synuclein gamma. AB - We recently identified and cloned novel breast cancer-specific gene BCSG1 by direct differential cDNA sequencing. BCSG1 has a great sequence homology with the Alzheimer's disease related neural protein synuclein (SNC); thus, it was also named SNC-gamma. Overexpression of SNC-gamma in breast cancer cells leads to a significant increase in motility and invasiveness in vitro and a profound augmentation of metastasis in vivo. Our data suggest that this member of the neural protein SNCs might have important functions outside the central nervous system and may play a role in breast cancer progression. PMID- 9973227 TI - Comparative genomic hybridization of cancer of the gastroesophageal junction: deletion of 14Q31-32.1 discriminates between esophageal (Barrett's) and gastric cardia adenocarcinomas. AB - Incidence rates have risen rapidly for esophageal and gastric cardia adenocarcinomas. These cancers, arising at and around the gastroesophageal junction (GEJ), share a poor prognosis. In contrast, there is no consensus with respect to clinical staging resulting in possible adverse effects on treatment and survival. The goal of this study was to provide more insight into the genetic changes underlying esophageal and gastric cardia adenocarcinomas. We have used comparative genomic hybridization for a genetic analysis of 28 adenocarcinomas of the GEJ. Eleven tumors were localized in the distal esophagus and related to Barrett's esophagus, and 10 tumors were situated in the gastric cardia. The remaining seven tumors were located at the junction and could not be classified as either Barrett-related, or gastric cardia. We found alterations in all 28 neoplasms. Gains and losses were distinguished in comparable numbers. Frequent loss (> or = 25% of all tumors) was detected, in decreasing order of frequency, on 4pq (54%), 14q (46%), 18q (43%), 5q (36%), 16q (36%), 9p (29%), 17p (29%), and 21q (29%). Frequent gain (> or = 25% of all tumors) was observed, in decreasing order of frequency, on 20pq (86%), 8q (79%), 7p (61%), 13q (46%), 12q (39%), 15q (39%), 1q (36%), 3q (32%), 5p (32%), 6p (32%), 19q (32%), Xpq (32%), 17q (29%), and 18p (25%). Nearly all patients were male, and loss of chromosome Y was frequently noted (64%). Recurrent high-level amplifications (> 10% of all tumors) were seen at 8q23-24.1, 15q25, 17q12-21, and 19q13.1. Minimal overlapping regions could be determined at multiple locations (candidate genes are in parentheses): minimal regions of overlap for deletions were assigned to 3p14 (FHIT, RCA1), 5q14 21 (APC, MCC), 9p21 (MTS1/CDKN2), 14q31-32.1 (TSHR), 16q23, 18q21 (DCC, P15) and 21q21. Minimal overlapping amplified sites could be seen at 5p14 (MLVI2), 6p12 21.1 (NRASL3), 7p12 (EGFR), 8q23-24.1 (MYC), 12q21.1, 15q25 (IGF1R), 17q12-21 (ERBB2/HER2-neu), 19q13.1 (TGFB1, BCL3, AKT2), 20p12 (PCNA), 20q12-13 (MYBL2, PTPN1), and Xq25. The distribution of the imbalances revealed similar genetic patterns in the three GEJ tumor groups. However, loss of 14q31-32.1 occurred significantly more frequent in Barrett-related adenocarcinomas of the distal esophagus, than in gastric cardia cancers (P = 0.02). The unclassified, "pure junction" group displayed an intermediate position, suggesting that these may be in part gastric cardia tumors, whereas the others may be related to (short segment) Barrett's esophagus. In conclusion, this study has, fist, provided a detailed comparative genomic hybridization-map of GEJ adenocarcinomas documenting new genetic changes, as well as candidate genes involved. Second, genetic divergence was revealed in this poorly understood group of cancers. PMID- 9973228 TI - Variants of squamous cell carcinoma of the anal canal and perianal skin and their relation to human papillomaviruses. AB - High-risk types of human papillomaviruses (hrHPVs) may be a necessary cause in cervical cancer and in some subtype of anal, vulvar, and penile cancers. Large studies aimed at characterizing hrHPV-associated and non-hrHPV-associated subtypes of anal carcinomas are, however, lacking. We searched for human papillomavirus type 16 and 13 other hrHPVs in tumor tissue by PCR and performed a systematic histological evaluation of specimens from 386 patients with anal cancer (86% invasive; 302 women and 84 men). Cancers in women and homosexual men were more often hrHPV positive (P < 0.01) and located in the anal canal (P < or = 0.01) than were cancers in heterosexual men. In both women and men, anal canal cancers contained hrHPV clearly more often than did perianal skin cancers, and increasing hrHPV positivity was seen with higher localization in the anal canal. Indeed, 95 and 83% of cancers involving the anal canal in women and men, respectively, were hrHPV positive versus 80 and 28% of perianal skin cancers (P trend < 0.001). Basaloid feature, adjacent anal intraepithelial neoplasia, poor or absent keratinization, and a predominance of small or medium neoplastic cells were all strongly positively associated with hrHPV status. Like cancer of the uterine cervix, the development of cancer of the anal canal may require infection with hrHPV, whereas a dual etiology of perianal skin cancers bears parallels to vulvar and penile cancers. PMID- 9973229 TI - Focal adhesion kinase-dependent apoptosis of melanoma induced by tyrosine and phenylalanine deficiency. AB - We found previously that restriction of tyrosine (Tyr) and phenylalanine (Phe) inhibited growth and metastasis of B16BL6 murine melanoma and arrested these cells in the G0-G1 phase of the cell cycle. Here, we report that deprivation of these two amino acids in vitro induces apoptosis in B16BL6 and in human A375 melanoma cells but not in nontransformed, neonatal murine epidermal cells or human infant foreskin fibroblasts. Four days after deprivation of Tyr and Phe in vitro, 37% of B16BL6 and 51% of A375 melanoma cells were undergoing apoptosis. Apoptosis was not associated with elevation in intracellular calcium or alteration in p53 or c-myc protein expression. Expression and Tyr phosphorylation of focal adhesion kinase (FAK) were inhibited in both melanoma cell lines by deprivation of Tyr and Phe but not by deprivation of glutamine or serum. Tyr phosphorylation of FAK in Tyr- and Phe-deprived melanoma cells was enhanced within 30 min of refeeding with complete DMEM. FAK protein expression recovered within 60 min, and cell viability recovered within 24 h. Genistein, a tyrosine kinase inhibitor that specifically inhibits Tyr phosphorylation of FAK, did not induce apoptosis in A375 melanoma cells at a concentration of 50 microM. Genistein prevented the recovery of cell viability upon refeeding with Tyr and Phe to previously deprived A375 melanoma cells. These data collectively indicate that apoptosis induced by Tyr and Phe deprivation is FAK-dependent. PMID- 9973230 TI - The 21-aminosteroid U-74389F attenuates hyperexpression of GAP-43 and NADPH diaphorase in the spinal cord of wobbler mouse, a model for amyotrophic lateral sclerosis. AB - The wobbler mouse suffers an autosomal recessive mutation producing severe neurodegeneration and astrogliosis in spinal cord. It has been considered a model for amyotrophic lateral sclerosis. We have studied in these animals the expression of two proteins, the growth-associated protein (GAP-43) and the NADPH diaphorase, the nitric oxide synthesizing enzyme, employing immunocytochemistry and histochemistry. We found higher expression of GAP-43 immunoreactivity in dorsal horn, Lamina X, corticospinal tract and ventral horn motoneurons in wobbler mice compared to controls. Weak NADPH-diaphorase activity was present in control motoneurons, in contrast to intense labeling of the wobbler group. No differences in diaphorase activity was measured in the rest of the spinal cord between control and mutant mice. A group of animals received subcutaneously for 4 days a 50 mg pellet of U-74389F, a glucocorticoid-derived 21-aminosteroid with antioxidant properties but without glucocorticoid activity. U-74389F slightly attenuated GAP-43 immunostaining in dorsal regions of the spinal cord from wobblers but not in controls. However, in motoneurons of wobbler mice number of GAP-43 immunopositive neurons, cell processes and reaction intensity were reduced by U-74389F. The aminosteroid reduced by 50% motoneuron NADPH-diaphorase activity. Hyperexpression of GAP-43 immunoreactivity in wobbler mice may represent an exaggerated neuronal response to advancing degeneration or muscle denervation. It may also be linked to increased nitric oxide levels. U-74389F may stop neurodegeneration and/or increase muscle trophism and stop oxidative stress, consequently GAP-43 hyperexpression was attenuated. Wobbler mice may be important models to evaluate the use of antioxidant steroid therapy with a view to its use in human motoneuron disease. PMID- 9973231 TI - Early treatment with cyclosporin A ameliorates the reduction of muscarinic acetylcholine receptors in gerbil hippocampus after transient forebrain ischemia. AB - Recent evidence has suggested that cyclosporin A (CsA), an immunosuppressive agent, has neuroprotective properties. However, its mechanisms associated with this activity remain unclear. We have previously shown that post-ischemic administration of CsA daily for 14 days prevented the decrease of muscarinic acetylcholine receptor binding in the hippocampus in the gerbil model of 5-min transient forebrain ischemia. In the present study, CsA (5 mg/kg, subcutaneously) was administered to each animal just after, 2 and 6 h after ischemia so as not to exert its immunosuppressive effect. Initial CsA treatment significantly restored the declined muscarinic acetylcholine receptor binding of the hippocampus 14 days after ischemia similar to the previous report. However, CsA did not alter reactive changes of astrocytes and microglia in the CA1 area of the hippocampus, which had been suppressed by daily administration. These results indicate that CsA could positively modulate the hippocampal acetylcholine neurotransmission system broken down through the ischemia-induced pyramidal cell death and its action mechanism may have no relation to the immunosuppressive properties. PMID- 9973232 TI - Effects of AF64A on gene expression of choline acetyltransferase (ChAT) in the septo-hippocampal pathway and striatum in vivo. AB - AF64A (ethylcholine mustard aziridinium ion) was stereotaxically administered bilaterally (1 nmol/side) into rat lateral cerebral ventricles. Choline acetyltransferase (ChAT) activity and ChAT mRNA levels were measured at predetermined time points in the septo-hippocampal pathway and striatum, both well identified as rich in cholinergic neurons. AF64A caused a rapid but transient increase in ChAT mRNA (167%, P < 0.05) and ChAT activity (164%, P < 0.01) in the septum. By day 7 post treatment, there was a significant decrease in ChAT mRNA (42.5% of control, P < 0.05) in the septum although the ChAT activity still stayed high. This decreased ChAT mRNA level in the septum lasted for at least four weeks, and was paralleled by a long-lasting decrease in ChAT activity in the hippocampus. In the striatum, on the other hand, there were no observed changes in either ChAT activity or ChAT mRNA. These data suggest that the long term effect of AF64A on the septo-hippocampal cholinergic pathway may, at least in part, be due to an action of AF64A on gene expression in the cholinergic neuron. The difference in the response to AF64A between the septo-hippocampal and striatal cholinergic systems might be due to their difference in neuron types. PMID- 9973233 TI - Differential effects of chemical sympathectomy on expression and activity of tyrosine hydroxylase and levels of catecholamines and DOPA in peripheral tissues of rats. AB - Tyrosine hydroxylase (TH) mRNA and activity and concentrations of 3,4 dihydroxyphenylalanine (DOPA) and catecholamines were examined as markers of sympathetic innervation and catecholamine synthesis in peripheral tissues of sympathectomized and intact rats. Chemical sympathectomy with 6-hydroxydopamine (6-OHDA) markedly decreased norepinephrine and to a generally lesser extent TH activities and dopamine in most peripheral tissues (stomach, lung, testis, duodenum, pancreas, salivary gland, spleen, heart, kidney, thymus). Superior cervical ganglia, adrenals and descending aorta were unaffected and vas deferens showed a large 92% decrease in norepinephrine, but only a small 38% decrease in TH activity after 6-OHDA. Presence of chromaffin cells or neuronal cell bodies in these latter tissues, indicated by consistent expression of TH mRNA, explained the relative resistance of these tissues to 6-OHDA. Stomach also showed consistent expression of TH mRNA before, but not after 6-OHDA, suggesting that catecholamine synthesizing cells in gastric tissue are sensitive to the toxic effects of 6-OHDA. Tissue concentrations of DOPA were mainly unaffected by 6 OHDA, indicating that much of the DOPA in peripheral tissues is synthesized independently of local TH or sympathetic innervation. The differential effects of chemical sympathectomy on tissue catecholamines, DOPA, TH mRNA and TH activity demonstrate that these variables are not simple markers of sympathetic innervation or catecholamine synthesis. Other factors, including presence of neuronal cell bodies, parenchymal chromaffin cells, non-neuronal sites of catecholamine synthesis and alternative sources of tissue DOPA, must also be considered when tissue catecholamines, DOPA and TH are examined as markers of sympathetic innervation and local catecholamine synthesis. PMID- 9973234 TI - Stimulation of immunoreactive insulin release by glucose in rat brain synaptosomes. AB - The effect of glucose on the release of immunoreactive insulin (IRI) in synaptosomes isolated from rat brain was studied. In the absence of glucose synaptosomes release about 4% (0.77 microIU/mg protein) of total content. Glucose increases significantly the IRI released by synaptosomes. Addition of the glycolytic inhibitor iodoacetic acid (IAA), decreased the glucose-induced release of IRI by about 50%, suggesting that glucose metabolism is involved. The observation that glucose provides a concentration related signal for IRI release indicates that this synaptosomal preparation may be useful as a model for research on the mechanism of insulin release in brain. PMID- 9973235 TI - Inactivation of the purified bovine mu opioid receptor by sulfhydryl reagents. AB - We have investigated the role of cysteine residues in a highly purified mu opioid receptor protein (muORP) by examining the effect of -SH reagents on the binding of opioid ligands. Treatment of muORP, which is devoid of additional proteins, eliminates complications that arise from reaction of -SH reagents with other components, such as G proteins. Reagents tested include N-ethylmaleimide, 5,5' dithiobis(2-nitrobenzoic) acid, and two derivatives of methanethiosulfonate. Specific opioid binding was inactivated by micromolar concentrations of all -SH reagents tested. Agonist binding ([3H]DAMGO) was much more sensitive to inactivation than antagonist binding ([3H]bremazocine). Prebinding muORP with 100 nM naloxone protected antagonist and agonist binding from inactivation by -SH reagents. The results of these experiments strongly suggest that at least one, and possibly more, reactive cysteine residue(s) is present on the mu opioid receptor protein molecule, positioned near the ligand binding site and accessible to -SH reagents. PMID- 9973236 TI - Immunohistochemical localization of calmodulin-dependent cyclic phosphodiesterase in the human brain. AB - The amplification of cyclic nucleotide 'second messenger' signals within neurons is controlled by phosphodiesterases which are responsible for their degradation. Calmodulin-dependent phosphodiesterase (CaMPDE) is an abundant enzyme in brain which carries out this function. For the first time, we have localized CaMPDE in the normal human brain at various ages, using a mononoclonal antibody designated A6. This antibody was generated using standard techniques, purified, and applied to tissue sections. Autopsy specimens of human brain with no neuropathological abnormalities were selected representing a range of pre- and postnatal ages. Sections of various brain regions were evaluated for immunoreactivity, graded as nil, equivocal, or definite. We demonstrated definite CaMPDE immunohistochemical staining in neocortex, especially in neurons in layers 2 and 5. There was definite neuronal immunoreactivity in the hippocampus, and in the subiculum. The striatum had definite patchy neuronal staining. Definite terminal staining in the globus pallidus externa and substantia nigra pars reticulata outlined resident neurons, interpreted as axonal terminal staining. Cerebellar Purkinje cells showed definite immunoreactivity. In the developing brain, definite immunohistochemical staining was seen in the cerebellar external granular layer. The expression of CaMPDE in specific subsets of neurons suggests they may correlate with cells having dopaminergic innervation and/or high levels of neuronal integration. PMID- 9973237 TI - Effect of ammonia and methionine sulfoximine on myo-inositol transport in cultured astrocytes. AB - Ammonia causes astrocyte swelling which is abrogated by methionine sulfoximine (MSO). Since myo-inositol is an important osmolyte, we investigated the effects of ammonia and MSO on myoinositol flux in cultured astrocytes for periods up to 72 hours. Uptake of myo-inositol was significantly decreased by 26.7 (P < 0.05) and 39.3 (P < 0.006) percent after 48 hours of exposure to 5 or 10 mM ammonia, respectively. The maximum rate of uptake was 14.0+/-0.5 nmol/hour/mg protein which was reduced to 7.45+/-0.27 and 7.02+/-0.57 nmoles/hour/mg protein by 5 or 10 mM ammonia, respectively. The Kms by Michaelis-Menten equation for the control, and in the presence of 5, or 10 mM ammonia were 32.5+/-4.52, 44.4+/ 5.82, and 39.3+/-7.0 microM, respectively. Kms by Hanes-Woolf plot for the control, 5, or 10 mM ammonia were 25, 45, and 40 microM, respectively. Treatment of astrocytes with either 5 or 10 mM NH4Cl for 6 hours caused a decrease in myo inositol content by 66% and 58%, respectively. MSO (3 mM) partially diminished the ammonia-induced inhibition of myo-inositol uptake and decreased myo-inositol content by 31% after 24 hours. Additionally, ammonia increased myo-inositol efflux briefly through the fast efflux component but had little effect on myo inositol efflux through the slow efflux component of astrocytes exposed to ammonia for up to 72 hours. Predominantly decreased myo-inositol influx coupled with brief efflux through the fast component may represent an adaptive response to diminish the extent of ammonia-induced astrocyte swelling. PMID- 9973238 TI - Interaction of nitric oxide donors and ascorbic acid on D-[3H] aspartate efflux from rat striatal slices. AB - There are conflicting reports in the literature concerning the neuroprotective effect of ascorbic acid on excitotoxic processes in which excessive glutamate release and nitric oxide are supposed to be major factors. To study the influence of ascorbate on the nitric oxide modulated glutamate release rat striatal slices, preloaded with the tritiated glutamate analog D-aspartate, were used. The high potassium-induced efflux of D-[3H]aspartate was concentration dependently stimulated by the nitric oxide donors sodium nitroprusside, S-nitroso-N acetylpenicillamine (SNAP) or 5-amino 3-morpholinyl-1,2,3-oxadiazolium chloride (SIN-1), as well as by solutions of gaseous nitric oxide and, interestingly, by cyanide. Only the stimulation of D-[3H]aspartate release by SNAP and nitroprusside was affected by ascorbate in terms of a highly significant potentiation. Ascorbate was shown to exert its effect primarily by influencing the decomposition of these nitric oxide donors rather than by a direct interaction of ascorbate with nitric monoxide on glutamate release. PMID- 9973240 TI - Effects of L-carnitine on the formation of fatty acid ethyl esters in brain and peripheral organs after short-term ethanol administration in rat. AB - A study was undertaken in rats to evaluate the effects of short-term oral ethanol administration on the levels of fatty acid ethyl esters (FAEE) in brain and peripheral organs in the presence and absence of pretreatment with L-carnitine. Administration of ethanol to rats for seven days resulted in fatty acid ethyl ester formation, particularly in the heart and brain, but also in the kidney and liver. FAEE generation was associated with a significant increase of GSH transferase activity. Treatment with L-carnitine significantly reduced both FAEE and GSH transferase activity, and these effects were associated with a significant decrease in alcohol blood concentrations. The present evidence supports the hypothesis that fatty acid ethyl esters could be mediators involved in the production of alcohol-dependent syndromes. Administration of L-carnitine through an increment in lipid metabolism and turnover, and by the modulation of cellular antioxidant enzymes, greatly reduces these metabolic abnormalities supporting its potential usefulness as a pharmacological tool in alcoholism management. PMID- 9973239 TI - U18666A inhibits intracellular cholesterol transport and neurotransmitter release in human neuroblastoma cells. AB - To determine if neurochemical function might be impaired in cell models with altered cholesterol balance, we studied the effects of U18666A (3-beta-[(2 diethyl-amino)ethoxy]androst-5-en-17-one) on intracellular cholesterol metabolism in three human neuroblastoma cell lines (SK-N-SH, SK-N-MC, and SH-SY5Y). U18666A (< or =0.2 microg/ml) completely inhibited low density lipoprotein (LDL) stimulated cholesterol esterification in SK-N-SH cells, while cholesterol esterification stimulated by 25-hydroxycholesterol or bacterial sphingomyelinase was unaffected or partially inhibited, respectively. U18666A also blocked LDL stimulated downregulation of LDL receptor and caused lysosomal accumulation of cholesterol as measured by filipin staining. U18666A treatment for 18 h resulted in 70% inhibition of K+-evoked norepinephrine release in phorbol ester differentiated SH-SY5Y cells, while release stimulated by the calcium ionophore A23187 was only slightly affected. These results suggest that U 18666A may preferentially block a voltage-regulated Ca2+ channel involved in norepinephrine release and that alterations in neurotransmitter secretion might be a feature of disorders such as Niemann-Pick Type C, in which intracellular cholesterol transport and distribution are impaired. PMID- 9973241 TI - Regulation of M1 muscarinic receptor-mediated signaling in intact cells by exogenous, but not endogenously produced, nitric oxide. AB - Regulation of nitric oxide (NO) formation is critical to ensure maintenance of appropriate cellular concentrations of this labile, signaling molecule. This study investigated the role exogenous and endogenously produced NO have in feeding back to regulate NO synthesis in intact cells. Two NO donors inhibited activation of neuronal NO synthase (nNOS) in response to the muscarinic receptor agonist carbachol in Chinese hamster ovary (CHO) cells stably transfected with the M1 muscarinic receptor and nNOS. The presence of the NO scavenger [2-(4 Carboxyphenyl)-4,4,5,5tetramethylimidazoline-1-oxyl-3-oxide potassium salt] (C PTIO) potentiated carbachol-induced activation of nNOS in transfected CHO cells. C-PTIO also potentiated nNOS activity in response to the Ca2+ ionophore ionomycin. In contrast, the NO scavenger oxyhemoglobin depressed carbachol- and ionomycin-induced NO formation. These discrepant results suggest that it is unlikely that endogenously produced NO induces feed back inhibition at the level of nNOS activation itself. Exogenous sources of NO inhibited carbachol-induced inositol phosphates formation. However, endogenously produced NO did not appear to feed back to regulate phosphoinositide hydrolysis as there was no difference in [3H]inositol phosphates formation between cells that do or do not express nNOS. There was also no change in carbachol-induced [3H]inositol phosphates formation in the presence or absence of a NOS inhibitor or the NO scavenger C PTIO. A decrease in the carbachol-mediated transient Ca2+ peak was observed in cells that express nNOS as compared to cells lacking the enzyme, suggesting that endogenous NO might inhibit receptor mediated Ca2+ signaling. This conclusion, however, was not supported by the lack of ability of a NOS inhibitor to modulate carbachol-induced Ca2+ elevations. Taken together, these results highlight differences in the regulation of the nNOS activation cascade by endogenous vs. exogenous sources of NO. PMID- 9973243 TI - Abstracts of the meeting of the fortieth anniversary of the oldest society for neurochemistry in the world: the Japanese Society for Neurochemistry (JSN). PMID- 9973242 TI - Presynaptic dopaminergic function in the nucleus accumbens following chronic opiate treatment and precipitated withdrawal. AB - Naloxone treatment at three days following implantation of pellets containing morphine base increased uptake of tritiated dopamine by the nucleus accumbens but did not alter efflux of tritiated dopamine by the nucleus accumbens or tritiated norepinephrine by the hippocampus. At six days following placement of pellets containing morphine base, withdrawal score was increased after treatment with either saline or naloxone, indicating that animals were undergoing spontaneous opiate withdrawal. Fractional efflux of tritiated dopamine was decreased at this time point following intermittent stimulation with 317 and 1000 microM 4 aminopyridine, for striatal slices obtained from animals pretreated with either saline or naloxone. For the nucleus accumbens at six days after placement of morphine pellets, similar decreases in the efflux of tritiated dopamine were only observed in slices obtained from naloxone treated animals. Fractional dopamine efflux was also diminished after in vitro exposure to rising concentrations of 4 aminopyridine, amphetamine, or cocaine for tissue obtained from the nucleus accumbens, but not for slices from the striatum at six days following morphine pellet implantation. In conclusion, deficits in dopamine efflux by the nucleus accumbens occur at a time when animals are undergoing spontaneous opiate withdrawal at six days following morphine pellet implantation, but do not occur at an earlier time point when withdrawal is precipitated by naloxone treatment. These deficits are apparent for brain slices obtained from the striatum or nucleus accumbens after exposure to rising concentrations of different in vitro treatments, with tissue obtained from the nucleus accumbens being more sensitive than the striatum to dopamine efflux produced by a wider range of treatments. PMID- 9973244 TI - Cytokine involvement in cancer anorexia/cachexia: role of megestrol acetate and medroxyprogesterone acetate on cytokine downregulation and improvement of clinical symptoms. AB - The characteristic clinical picture of anorexia, tissue wasting, loss of body weight accompanied by a decrease in muscle mass and adipose tissue, and poor performance status that often precedes death has been named the cancer-related anorexia/cachexia syndrome (CACS). Chronic administration of pro-inflammatory cytokines, including interleukin-1 (IL-1), interleukin-6 (IL-6), and tumor necrosis factor (TNF) either alone or in combination, is capable of reproducing the different features of CACS. High serum levels of these cytokines have been found in cancer patients, which seem to correlate with progression of the tumor. This paper describes a series of experimental and clinical studies demonstrating that: (1) high serum levels of some cytokines, including IL-1, IL-6, and TNF, are present in advanced-stage cancer patients, particularly those with CACS; (2) megestrol acetate (MA) has a beneficial therapeutic effect on CACS symptoms, such as appetite, body weight, and quality-of-life; (3) MA downregulates the synthesis and release of cytokines and relieves the symptoms of CACS; (4) cytokines play a key role in the onset of CACS; (5) medroxyprogesterone acetate (MPA) reduces the in vitro production of cytokines and serotonin (5-hydroxytryptamine, 5-HT) by peripheral blood mononuclear cells (PBMC) of cancer patients; and (6) MA and MPA reduce the cisplatin-induced 5-HT release in vitro from PBMC of cancer patients. Based on these results, a clinical study incorporating MA/MPA in combination with chemotherapy or chemoimmunotherapy may be warranted. PMID- 9973245 TI - Kaposi's sarcoma pathogenesis: a link between immunology and tumor biology. AB - Kaposi's sarcoma (KS) was a rare disease in Europe and North America until a decade ago, when it became the most common neoplasm complicating the acquired immunodeficiency syndrome (AIDS), where it acquires an aggressive course. Clinical and experimental data suggest that, at least in early stage, KS may not be a true sarcoma, but an hyperplastic-proliferative lesion that may regress. At least three components characterize KS lesions: (1) neoangiogenesis and proliferation of spindle-shaped cells of endothelial and macrophage cell origin, some of which may originate from a circulating precursor; (2) a cellular infiltrate represented by macrophages, lymphoid cells, mast cells, and neutrophils; and (3) the infection of spindle cells and mononuclear cells with a new virus of the Herpesvirinae family defined KS-associated herpesvirus or human herpesvirus-8 (HHV-8). KS lesions are highly responsive, in terms of growth, to inflammatory cytokines (IC) and many lesional cell components are able to secrete cytokines and chemokines, which induce paracrine-autocrine mechanisms of growth, angiogenesis, and promote further cellular recruitment. The association between HHV-8 and KS is close; however, the role of the virus in KS development is yet unknown. Nevertheless, the virus has the potential to encode for homologs of cellular cytokines and some chemokines and its reactivation is sensitive to stimuli provided by IC. This review focuses on these aspects of KS pathogenesis, trying to reconcile many of the clinical and experimental observations. Finally, the role of the HIV-1 Tat protein as a factor of progression in AIDS-KS as well as the role of cellular and HHV-8 encoded proto-oncogenes as factors and markers of progression of KS to a true malignancy is reviewed. PMID- 9973246 TI - The molecular biology of breast cancer: accelerating clinical applications. AB - Recent advances in basic science have led to a better understanding of the molecular events important in the pathogenesis of breast cancer. Very little of this new knowledge, however, has had a significant impact on improving the diagnosis and therapy of breast cancer. We review many of the molecular events important in the pathogenesis of breast cancer, including inherited abnormalities in BRCA-1 and BRCA-2, p53, ATM, and PTEN and sporadic alterations in growth factors and their receptors, signal transduction, cell cycle control, DNA repair, cell death, angiogenesis, and invasion and metastasis. We suggest ways to speed up clinical applications of the new molecular knowledge base through the use of preclinical disease models, development of high throughput sample analysis and infrastructure programs to facilitate translational research, implementation of practice guidelines, and development of regional oncology networks. Only through the implementation of such a deliberate, multifaceted strategy will the gap between the research laboratory and the clinic be closed. PMID- 9973247 TI - The role of Pax3 and Pax7 in development and cancer. AB - Pax genes consist of a family of transcription factors that are essentially required for the genesis of a variety of tissues and organs. Pax3 and Pax7 are specifically expressed in the dorsal neural tube and the developing somite. Loss of-function mutations of Pax3 in Splotch mice and in Waardenburg syndrome in man revealed that Pax3 is necessary for the proper formation of caudal neural crest derivatives and for the migration of myoblasts into the limb. Mice with a mutated Pax7 gene suffer from defects in cephalic neural crest derivatives only and indicate that both genes may functionally share some redundancy. Gain-of-function mutations creating fusion proteins consisting of PAX3 or PAX7 and another transcription factor of the forkhead family (FKHR) are associated with alveolar rhabdomyosarcomas. The analyses of Pax3 and Pax7 function in normal development indicate that Pax3 (possibly also Pax7) triggers neoplastic development by maintaining cells in a deregulated undifferentiated and proliferative state in alveolar rhabdomyosarcomas. PMID- 9973248 TI - Chronic retroviruses and oncogenesis. AB - Chronic retroviruses are associated with both malignant and nonmalignant diseases in vertebrates. This review addresses the pathogenetic basis of neoplastic processes that have been directly or indirectly associated with chronic retroviruses. PMID- 9973249 TI - Role of the third intracellular loop for the activation of gonadotropin receptors. AB - Hyperfunctional endocrine thyroid and testicular disorders can frequently be traced back to gainof-function mutations in glycoprotein hormone receptor genes. Deletion mutations in the third intracellular (i3) loop of the TSH receptor have recently been identified as a cause of constitutive receptor activity. To examine whether the underlying mechanism of receptor activation applies to all glycoprotein hormone receptors, we created deletion mutations in the LH and FSH receptors. In analogy to the situation with the TSH receptor, a deletion of nine amino acids resulted in constitutive activity irrespective of the location of deletions within the i3 loop of the LH receptor. In contrast, only one (delta563 566) of four different 4-amino acid deletion mutants displayed agonist independent activity. Systematic examination of the structural requirements for this effect in the delta563-566 mutant revealed that only deletions including D564 resulted in constitutive receptor activity. Replacement of D564 by G, K, and N led to agonist-independent cAMP formation while introduction of a negatively charged E silenced constitutive receptor activity, indicating that an anionic amino acid at this position may be required to maintain an inactive receptor conformation. Insertion of A residues up- and downstream of D564 did not perturb receptor quiescence, showing that a certain degree of spatial freedom of the negatively charged amino acid within the context of the i3 loop is well tolerated. In contrast to the results obtained with the LH receptor, deletion of the corresponding D567 from the i3 loop of the FSH receptor did not cause constitutive receptor activation, highlighting significant differences in the activation mechanism of gonadotropin receptors. PMID- 9973251 TI - Subcellular distribution and function of Rab3A, B, C, and D isoforms in insulin secreting cells. AB - Insulin-secreting cells express four GTPases of the Rab3 family. After separation of extracts of INS-1 cells on a sucrose density gradient, the bulk of the A, B, and C isoforms was recovered in the fractions enriched in insulin-containing secretory granules. Rab3D was also mainly associated with secretory granules, but a fraction of this isoform was localized on lighter organelles. Analyses by confocal microscopy of immunostained HIT-T15 cells transfected with epitope tagged constructs confirmed the distribution of the Rab3 isoforms. Transfection of HIT-T15 cells with GTPase-deficient mutants of the Rab3 isoforms decreased nutrient-induced insulin release to different degrees (D>B>A>>C), while overexpression of Rab3 wild types had minor or no effects. Expression of the same Rab3 mutants in PC12 cells provoked an inhibition of K+-stimulated secretion of dense core vesicles, indicating that, in beta-cells and neuroendocrine cells, the four Rab3 isoforms play a similar role in exocytosis. A Rab3A/C chimera in which the carboxyterminal domain of A was replaced with the corresponding region of C inhibited insulin secretion as Rab3A. In contrast, a Rab3C/A chimera containing the amino-terminal domain of C was less potent and reduced exocytosis as Rab3C. This suggests that the degree of inhibition obtained after transfection of the Rab3 isoforms is determined by differences in the variable amino-terminal region. PMID- 9973250 TI - Growth arrest-specific gene 6 (Gas6)/adhesion related kinase (Ark) signaling promotes gonadotropin-releasing hormone neuronal survival via extracellular signal-regulated kinase (ERK) and Akt. AB - We identified Ark, the mouse homolog of the receptor tyrosine kinase Axl (Ufo, Tyro7), in a screen for novel factors involved in GnRH neuronal migration by using differential-display PCR on cell lines derived at two windows during GnRH neuronal development. Ark is expressed in Gn10 GnRH cells, developed from a tumor in the olfactory area when GnRH neurons are migrating, but not in GT1-7 cells, derived from a tumor in the forebrain when GnRH neurons are postmigratory. Since Ark (Ax1) signaling protects from programmed cell death in fibroblasts, we hypothesized that it may play an antiapoptotic role in GnRH neurons. Gn10 (Ark positive) GnRH cells were more resistant to serum withdrawal-induced apoptosis than GT1-7 (Ark negative) cells, and this effect was augmented with the addition of Gas6, the Ark (Ax1) ligand. Gas6/Ark stimulated the extracellular signal regulated kinase, ERK, and the serine-threonine kinase, Akt, a downstream component of the phosphoinositide 3-kinase (PI3-K) pathway. To determine whether ERK or Akt activation is required for the antiapoptotic effects of Gas6/Ark in GnRH neurons, cells were serum starved in the absence or presence of Gas6, with or without inhibitors of ERK and PI3-K signaling cascades. Gas6 rescued Gn10 cells from apoptosis, and this effect was blocked by coincubation of the cells with the mitogen-activated protein/ERK kinase (MEK) inhibitor, PD98059, or wortmannin (but not rapamycin). These data support an important role for Gas6/Ark signaling via the ERK and PI3-K (via Akt) pathways in the protection of GnRH neurons from programmed cell death across neuronal migration. PMID- 9973252 TI - Down-regulation of liver JAK2-STAT5b signaling by the female plasma pattern of continuous growth hormone stimulation. AB - The suppression of male-specific, GH pulse-induced, liver transcription in adult female rats has been linked to the down-regulation of STAT5b activation by the female plasma pattern of near-continuous GH exposure. The mechanism underlying this down-regulation was studied in the rat liver cell line CWSV-1, where continuous GH suppressed the level of activated (tyrosine- phosphorylated) STAT5b to approximately 10-20% of the maximal GH pulse-induced STAT5b signal within 3 h. In contrast to the robust JAK2 kinase-dependent STAT5b activation loop that is established by a GH pulse, JAK2 kinase signaling to individual STAT5b molecules was found to be short lived in cells treated with GH continuously. Moreover, maintenance of the low-level STAT5b signal required ongoing protein synthesis and persisted for at least 7 days provided that GH was present in the culture continuously. Increased STAT5b DNA-binding activity was observed in cells treated with the proteasome inhibitor MG132, suggesting that at least one component of the GH receptor (GHR)-JAK2-STAT5b signaling pathway becomes labile in response to continuous GH treatment. The phosphotyrosine phosphatase inhibitor pervanadate fully reversed the down-regulation of STAT5b DNA-binding activity in continuous GH-treated cells by a mechanism that involves both increased STAT5b activation and decreased STAT5b dephosphorylation. Moreover, the requirement for ongoing GH stimulation and active protein synthesis to maintain STAT5b activity in continuous GH-treated cells were both eliminated by pervanadate treatment, suggesting that phosphotyrosine dephosphorylation may be an obligatory first step in the internalization/degradation pathway for the GHR-JAK2 complex. Finally, the sustaining effect of the serine kinase inhibitor H7 on GH pulse-induced JAK2 signaling to STAT5b was not observed in continuous GH-treated cells. These findings suggest a model where continuous GH exposure of liver cells down regulates the STAT5b pathway by a mechanism that involves enhanced dephosphorylation of both STAT5b and GHR-JAK2, with the latter step leading to increased internalization/degradation of the re-ceptor-kinase complex. PMID- 9973253 TI - Reconstitution of the protein kinase A response of the rat prolactin promoter: differential effects of distinct Pit-1 isoforms and functional interaction with Oct-1. AB - PRL gene transcription is primarily regulated by dopamine, which lowers cAMP levels and inhibits protein kinase A (PKA) activity. Current data indicate that the cAMP/PKA response maps to the most proximal Pit-1/Pit-1beta binding site footprint I (FP I) on the rat PRL (rPRL) promoter. Pit-1, a POU-homeo domain transcription factor, is specifically expressed in the anterior pituitary and is required both for the normal development of anterior pituitary cell types, somatotrophs, lactotrophs, and thyrotrophs, and for the expression of their hormones: GH, PRL, and TSHbeta. Pit-1 has been shown to functionally interact, via FP I, with several transcription factors, including Oct-1, a ubiquitous homeobox protein, and thyrotroph embryonic factor, which is found in lactotrophs, to activate basal rPRL promoter activity. Pit-1beta/GHF-2, a distinct splice isoform of Pit-1, acts to inhibit Ras-activated transcription from the rPRL promoter, which is mediated by a functional interaction between Pit-1 and Ets-1 at the most distal Pit-1 binding site (FP IV). In this manuscript we show 1) that the Pit-1beta isoform not only fails to block PKA activation, but is, in fact, a superior mediator of the PKA response; 2) that the PKA response requires intact POU-specific and POU-homeo domains of Pit-1; and 3) that Oct-1, but not thyrotroph embryonic factor, functions as a Pit-1-interacting factor to mediate an optimal PKA response. PMID- 9973254 TI - Stimulation of aromatase P450 promoter (II) activity in endometriosis and its inhibition in endometrium are regulated by competitive binding of steroidogenic factor-1 and chicken ovalbumin upstream promoter transcription factor to the same cis-acting element. AB - In stromal cells of endometriosis, marked levels of aromatase P450 (P450arom) mRNA and activity are present and can be vigorously stimulated by (Bu)2cAMP or PGE2 to give rise to physiologically significant estrogen biosynthesis. Since eutopic endometrial tissue or stromal cells lack P450arom expression, we studied the molecular basis for differential P450arom expression in endometriosis and eutopic endometrium. First, we demonstrated by rapid amplification of cDNA 5' ends that P450arom expression in pelvic endometriotic lesions is regulated almost exclusively via the alternative promoter II. Then, luciferase reporter plasmids containing deletion mutations of the 5'-flanking region of promoter II were transfected into endometriotic stromal cells. We identified two critical regulatory regions for cAMP induction of promoter II activity: 1) a-214/-100 bp proximal region responsible for a 3.7-fold induction, and 2) a -517/ -214 distal region responsible for potentiation of cAMP response up to 13-fold. In the -214/ 100 region, we studied eutopic endometrial and endometriotic nuclear protein binding to a nuclear receptor half-site (NRHS, AGGTCA) and an imperfect cAMP response element (TGCACGTCA). Using electrophoretic mobility shift assay, cAMP response element-binding activity in nuclear proteins from both endometriotic and eutopic endometrial cells gave rise to formation of identical DNA-protein complexes. The NRHS probe, on the other hand, formed a distinct complex with nuclear proteins from endometriotic cells, which migrated at a much faster rate compared with the complex formed with nuclear proteins from eutopic endometrial cells. Employing recombinant proteins and antibodies against steroidogenic factor 1 (SF-1) and chicken ovalbumin upstream promoter transcription factor (COUP-TF), we demonstrated that COUP-TF but not SF-1 bound to NRHS in eutopic endometrial cells, whereas SF-1 was the primary NRHS-binding protein in endometriotic cells. In fact, COUP-TF transcripts were present in both eutopic endometrial (n = 12) and endometriotic tissues (n = 8), whereas SF-1 transcripts were detected in all endometriotic tissues (n = 12), but in only 3 of 15 eutopic endometrial tissues. Moreover, we demonstrated a dose-dependent direct competition between SF-1 and COUP-TF for occupancy of the NRHS, to which SF-1 bound with a higher affinity. Finally, overexpression of SF-1 in eutopic endometrial and endometriotic cells strikingly potentiated baseline and cAMP-induced activities of -517 promoter II construct, whereas overexpression of COUP-TF almost completely abolished these activities. In conclusion, COUP-TF might be one of the factors responsible for the inhibition of P450arom expression in eutopic endometrial stromal cells, which lack SF-1 expression in the majority (80%) of the samples; in contrast, aberrant SF-1 expression in endometriotic stromal cells can override this inhibition by competing for the same DNA-binding site, which is likely to account for high levels of baseline and cAMP-induced aromatase activity. PMID- 9973255 TI - The Adrenomedullin gene is a target for negative regulation by the Myc transcription complex. AB - The Myc family of transcription factors plays a central role in vertebrate growth and development although relatively few genetic targets of the Myc transcription complex have been identified. In this study, we used mRNA differential display to investigate gene expression changes induced by the overexpression of the MC29 v Myc oncoprotein in C3H10T1/2 mouse fibroblasts. We identified the transcript of the adrenomedullin gene (AM) as an mRNA that is specifically down-regulated in v Myc overexpressing C3H10T1/2 cell lines as well as in a Rat 1a cell line inducible for c-Myc. Nucleotide sequence analysis of the mouse AM promoter reveals the presence of consensus CAAT and TATA boxes as well as an initiator element (INR) with significant sequence similarity to the INR responsible for Myc mediated repression of the adenovirus major late promoter (AdMLP). Reporter gene assays confirm that the region of the AM promoter containing the INR is the target of Myc-mediated repression. Exogenous application of AM peptide to quiescent C3H10T1/2 cultures does not stimulate growth, and constitutive expression of AM mRNA in C3H10T1/2 cells correlates with a reduced potential of the cells to be cotransformed by v-Myc and oncogenic Ras p21. Additional studies showing that AM mRNA is underrepresented in C3H10T1/2 cell lines stably transformed by Ras p21 or adenovirus E1A suggest that AM gene expression is incompatible with deregulated growth in this cell line. We propose a model in which the repression of AM gene expression by Myc is important to the role of this oncoprotein as a potentiator of cellular transformation in C3H10T1/2 and perhaps other cell lines. PMID- 9973256 TI - A novel mechanism for cyclic adenosine 3',5'-monophosphate regulation of gene expression by CREB-binding protein. AB - The pituitary-specific transcription factor, Pit-1, is necessary to mediate protein kinase A (PKA) regulation of the GH, PRL, and TSH-beta subunit genes in the pituitary. Since these target genes lack classical cAMP DNA response elements (CREs), the mechanism of this regulation was previously unknown. We show that CREB binding protein (CBP), through two cysteine-histidine rich domains (C/H1 and C/H3), specifically and constitutively interacts with Pit-1 in pituitary cells. Pit-1 and CBP synergistically activate the PRL gene after PKA stimulation in a mechanism requiring both an intact Pit-1 amino-terminal and DNA-binding domain. A CBP construct containing the C/H3 domain [amino acids (aa) 1678-2441], but not one lacking the C/H3 domain (aa 1891-2441), is sufficient to mediate this response. Neither construct augments PKA regulation of CRE-containing promoters. Fusion of either CBP fragment to the GAL4 DNA-binding domain transferred complete PKA regulation to a heterologous promoter. These findings provide a mechanism for CREB-independent regulation of gene expression by cAMP. PMID- 9973257 TI - Ligand-activated retinoic acid receptor inhibits AP-1 transactivation by disrupting c-Jun/c-Fos dimerization. AB - In the presence of retinoic acid (RA), the retinoid receptors, retinoic acid receptor (RAR) and retinoid X receptor (RXR), are able to up-regulate transcription directly by binding to RA-responsive elements on the promoters of responsive genes. Liganded RARs and RXRs are also capable of down-regulating transcription, but, by contrast, this is an indirect effect, mediated by the interaction of these nuclear receptors not with DNA but the transcription factor activating protein-1 (AP-1). AP-1 is a dimeric complex of the protooncoproteins c Jun and c-Fos and directly regulates transcription of genes important for cellular growth. Previous in vitro results have suggested that RARs can block AP 1 DNA binding. Using a mammalian two-hybrid system, we report here that human RARalpha (hRARalpha) can disrupt in a RA-dependent manner the homo- and heterodimerization properties of c-Jun and c-Fos. This inhibition of dimerization is cell specific, occurring only in those cells that exhibit RA-induced repression of AP-1 transcriptional activity. Furthermore, this mechanism appears to be specific for the RARs, since another potent inhibitor of AP-1 activity, the glucocorticoid receptor, does not affect AP-1 dimerization. Our data argue for a novel mechanism by which RARs can repress AP-1 DNA binding, in which liganded RARs are able to interfere with c-Jun/c-Jun homodimerization and c-Jun/c-Fos heterodimerization and, in this way, may prevent the formation of AP-1 complexes capable of DNA binding. PMID- 9973258 TI - Estrogen receptor domains E and F: role in dimerization and interaction with coactivator RIP-140. AB - We have used the yeast two-hybrid system to localize the ligand-dependent dimerization domain of the estrogen receptor-alpha (ER) to region E in vivo. In this system, the cDNAs corresponding to the A-D, E, E/F, A-E (deltaF), and full length (wtER) domains of the human ER were each cloned into the yeast two-hybrid vectors GAL4 DB and GAL4 TA and expressed in different combinations in yeast harboring a GAL1-lacZ reporter. The reporter was used as a relative measure of the interaction between the ER domains, through reconstitution of GAL4 activity. We found that the interaction of E or E/F domains of the ER with full-length ER is estradiol dependent and estrogen responsive element independent, as measured by the reconstitution of GAL4 activity from GAL4-E domain-containing fusion protein interactions. In the presence of F domain, this activity is reduced 10 fold. The results suggest that sequences in the F domain are inhibitory to the dimerization signal that is present in the E region. We propose that the full length ER contains intrinsic dimerization restraints contributed by regions outside domain E that are released upon binding hormone agonist. In addition, we have demonstrated that coactivator RIP140 is able to interact with the ER in vivo at the E domain of the receptor in the presence of estrogen. Yeast two-hybrid analysis shows that RIP140 does not homodimerize in the presence or absence of estrogens. We present evidence showing that the ER has the inherent ability to interact with RIP140 in the presence of antiestrogens, but sequences inherent in the ER itself that are present outside of the E domain compromise this ability. PMID- 9973259 TI - Effects of mineralocorticoid receptor gene disruption on the components of the renin-angiotensin system in 8-day-old mice. AB - Targeted disruption of mineralocorticoid receptor (MR) gene results in pseudohypoaldosteronism type I with failure to thrive, severe dehydration, hyperkalemia, hyponatremia, and high plasma levels of renin, angiotensin II, and aldosterone. In this study, mRNA expression of the different components of the renin-angiotensin system (RAS) were evaluated in liver, lung, heart, kidney and adrenal gland to assess their response to a state of extreme sodium depletion. Angiotensinogen, renin, angiotensin-I converting enzyme, and angiotensin II receptor (AT1 and AT2) mRNA expressions were determined by Northern blot and RT PCR analysis. Furthermore, in situ hybridization and immunohistochemistry allowed us to identify the cell types involved in the variation of the RAS component expression. In the heterozygous mice (MR+/-), compared with wild-type mice (MR+/+), there was no significant variation of any mRNA of the RAS components. In MR knockout mice (MR-/-), compared with wild-type mice, there were significant increases in the expression level of several RAS components. In the liver, angiotensinogen and AT1 receptor mRNA expressions were moderately stimulated. In the kidney, renin mRNA was increased up to 10-fold and in situ hybridization showed a marked recruitment of renin-producing cells; however, the levels of angiotensin-I converting enzyme mRNA and AT1 mRNA were not changed. Interestingly, in adrenal gland, renin expression was also strongly up-regulated in a thickened zona glomerulosa, whereas AT1 mRNA expression remained unchanged. Altogether, these results demonstrate that in the MR knockout mice model, RAS component expressions are differentially altered, renin being the most stimulated component. Angiotensinogen and AT1 in the liver are also increased, but the other elements of the RAS are not affected. PMID- 9973260 TI - Cell membrane and nuclear estrogen receptors (ERs) originate from a single transcript: studies of ERalpha and ERbeta expressed in Chinese hamster ovary cells. AB - The existence of a putative membrane estrogen receptor (ER) has been supported by studies accomplished over the past 20 yr. However, the origin and functions of this receptor are not well defined. To study the membrane receptor, we transiently transfected cDNAs for ERalpha or ERbeta into Chinese hamster ovary (CHO) cells. Transfection of ERalpha resulted in a single transcript by Northern blot, specific binding of labeled 17beta-estradiol (E2), and expression of ER in both nuclear and membrane cell fractions. Competitive binding studies in both compartments revealed near identical dissociation constants (K(d)S) of 0.283 and 0.287 nM, respectively, but the membrane receptor number was only 3% as great as the nuclear receptor density. Transfection of ERbeta3 also yielded a single transcript and nuclear and membrane receptors with respective Kd values of 1.23 and 1.14 nM; the membrane receptor number was only 2% compared with expressed nuclear receptors. Estradiol binding to CHO-ERalpha or CHO-ERbeta activated Galphaq and G(alpha)s proteins in the membrane and rapidly stimulated corresponding inositol phosphate production and adenylate cyclase activity. Binding by 17-beta-E2 to either expressed receptor comparably enhanced the nuclear incorporation of thymidine, critically dependent upon the activation of the mitogen-activated protein kinase, ERK (extracellular regulated kinase). In contrast, c-Jun N-terminal kinase activity was stimulated by 17-beta-E2 in ERbeta expressing CHO, but was inhibited in CHO-ERalpha cells. In summary, membrane and nuclear ER can be derived from a single transcript and have near-identical affinities for 17-beta-E2, but there are considerably more nuclear than membrane receptors. This is also the first report that cells can express a membrane ERbeta. Both membrane ERs activate G proteins, ERK, and cell proliferation, but there is novel differential regulation of c-Jun kinase activity by ERbeta and ERalpha. PMID- 9973261 TI - Transcriptional regulation by a naturally occurring truncated rat estrogen receptor (ER), truncated ER product-1 (TERP-1). AB - Truncated estrogen receptor product-1 (TERP-1) is a naturally occurring rat estrogen receptor (ER) variant transcribed from a unique start site and containing a unique 5'-untranslated region fused to exons 5-8 of ERalpha. TERP-1 is detected only in the pituitary, and TERP-1 mRNA levels are highly regulated during the estrous cycle, exceeding those of the full-length ERalpha on proestrus. These data suggest that TERP-1 may play a role in estrogen- regulated feedback in the pituitary. We examined the ability of TERP-1 to modulate gene transcription in transiently transfected ER-negative (Cos-1) and ER-positive pituitary (alphaT3 and GH3) cell lines. In Cos-1 cells transiently cotransfected with TERP-1 and either ERalpha or ERbeta, low levels of TERP-1 (ratios of < 1:1 with ER) enhanced transcription of model promoters containing estrogen response elements by an average of 3- to 4-fold above that seen with ER alone. At higher concentrations of TERP-1 (> 1:1 with ER) transcription was inhibited. TERP-1 also had a biphasic action on transcription in the alphaT3 and GH3 pituitary cell lines, although the stimulatory action was less pronounced. TERP-1 actions were dependent on ligand-activated ER as TERP-1 did not bind estradiol in transfected Cos-1 cells or in vitro, and estrogen antagonists prevented the stimulatory effects of TERP-1. Coimmunoprecipitation studies suggest that TERP-1 does not bind with high affinity to the full-length ERalpha. However, TERP-1 may compete with ER for binding sites of receptor cofactors because steroid receptor coactivator-1 (SRC-1) rescued the inhibitory actions of TERP-1. The ability of TERP-1 to both enhance and inhibit ER-dependent promoter activity suggests that TERP-1 may play a physiological role in estrogen feedback in the rat pituitary. PMID- 9973262 TI - Glucocorticoid receptor/signal transducer and activator of transcription 5 (STAT5) interactions enhance STAT5 activation by prolonging STAT5 DNA binding and tyrosine phosphorylation. AB - The regulation of casein gene expression by both PRL and glucocorticoids has been a well studied paradigm for understanding how the signaling pathways regulated by these two hormones interact in the nucleus. Previous studies have demonstrated that the downstream effectors of these pathways, signal transducer and activator of transcription 5 (STAT5) and the glucocorticoid receptor (GR), are associated via protein-protein interactions and act synergistically to enhance beta-casein gene transcription. Indirect immunofluorescence microscopy was used to demonstrate that PRL-activated STAT5 can translocate GR into the nucleus, and that ligand-bound GR can translocate STAT5 into the nucleus. This provided further support of an interaction between the two proteins. To better understand the mechanism of transcriptional synergy between STAT5 and GR, experiments were performed in cells transiently transfected with STAT5 alone or with STAT5 and GR. GR cotransfection enhanced the DNA-binding activity of STAT5 without affecting STAT5 protein levels. The enhancement of STAT5 DNA binding by GR resulted in the formation of a complex that exhibited prolonged DNA binding after PRL treatment. This was correlated with increased STAT5 tyrosine phosphorylation, suggesting that GR enhances STAT5 DNA binding by modulating the rate of STAT5 dephosphorylation. In contrast, cotransfection of the estrogen receptor resulted in an overall decrease in STAT5 tyrosine phosphorylation, without changing the kinetics of dephosphorylation. Enhancement of STAT5 activity by GR is, therefore, one component of the transcriptional synergy exhibited by STAT5 and GR at the beta-casein promoter and is an example of how transcription factors at a composite response element may modulate each other's activity. PMID- 9973263 TI - D5 dopamine receptors mediate estrogen-induced stimulation of hypothalamic atrial natriuretic factor neurons. AB - Whereas progesterone and dopamine share a common central pathway to modulate sexual behavior in female rats, the way in which estrogen is involved remains unclear. In a long-term rat hypothalamic cell culture system, atrial natriuretic factor-producing neurons were identified as candidate sites for integration of sex steroid action. Estrogen induces the expression of progesterone receptors in atrial natriuretic factor neurons and also augments neuronal functions by increasing expression of constitutively active D5 receptors that generate cAMP in a ligand-independent manner. Such a cross-talk mechanism allows estrogen to exert its effects via the adenylyl cyclase-cAMP system by augmenting dopamine receptor activity, an action that may play an important integrative role in facilitating female sexual behavior. PMID- 9973264 TI - Annual physiological changes in individually housed squirrel monkeys (Saimiri sciureus). AB - This study investigated whether annual changes in physiology occur in individually housed squirrel monkeys (Saimiri sciureus). Physiological measures were monitored for 20 months. Over the course of the study, all individually housed males and females exhibited clear annual changes in gonadal and adrenal hormone levels, and males exhibited species-typical changes in body weight. Females exhibited a typical pattern of hormonal changes, with elevations in gonadal steroids occurring during the same months as elevations in cortisol. Males, however, exhibited an atypical pattern, as elevations in hormone levels were not synchronized with each other; rather, elevations in testosterone occurred out of phase with changes in cortisol and body weight. The timing of annual events in individually housed subjects was compared to that in nearby social groups, in which the timing of the breeding season from year to year was determined by social group formations and was outside the naturally occurring breeding season. Elevations of ovarian and adrenocortical hormones in individually housed females were synchronized with indices of breeding in heterosexual social groups. Similarly, weight gain in males was associated with elevations in cortisol and, as with socially housed males, tended to precede seasonal breeding in the social groups. In contrast, annual testosterone elevations for individually housed males were not synchronized with breeding in nearby social groups. We conclude that direct physical interaction is not required for the annual expression of breeding readiness. Synchrony of seasonality among squirrel monkeys may be accomplished by distant social cues in females, but males may require physical interaction for complete synchrony of annual physiological changes. PMID- 9973265 TI - Morphological characterization of ejaculated cynomolgus monkey (Macaca fascicularis) sperm. AB - The aim of this study was to give reference values for the frequency of morphological sperm abnormalities present in the semen from non-experimental cynomolgus monkeys as well as for the dimensions of sperm heads. Spermatozoa from the liquid portion of electroejaculates from 14 cynomolgus monkeys were air-dried as smears, fixed, and stained with Harris's Haematoxylin and subjected to visual analysis of morphology and computer-aided analysis of ten morphometric variables. The majority (83%) of sperm were morphologically normal. Tail defects were the most common (11%), and showed the highest variation between individuals, the values ranging between 4 and 23%. Head abnormalities consisted of large, tapering, and amorphous forms but were not frequent (0.4%), the values ranging between 0 and 1.3%. Midpiece imperfections were found in all the individuals; the mean percentage was 5%, and the range varied between 3 and 9%. Tail plus midpiece was the only multiple abnormality observed, with a mean value of 1.5% and a range between 0 and 8%. The majority of these double defects consisted of a coiled tail together with a coiled midpiece. Mean values for the morphometric parameters characterizing sperm heads were as follows: area 17.2 microm2, perimeter 15.2 microm, length 5.8 microm, width 4.0 microm, L/W ratio 1.5, gray-level 98, ellipticity 0.2, first shape factor 0.9, second shape factor 1.4, and third shape factor 1.1. Overall coefficients of variation for the majority of parameters were below 7%, showing the great homogeneity in the dimensions of cynomolgus sperm heads. Most useful parameters for sperm characterization, according to their low variability, were perimeter, length, width, L/W ratio, and shape factors. Differences in these parameters were, however, observed between monkeys. PMID- 9973266 TI - Perception of novel changes in a familiar environment by socially-housed rhesus monkeys. AB - Many animals appear to have a sophisticated spatial representation of their environment. The development of these representations depends on the joint abilities of discriminating novel objects and remembering their locations. Variations of a detection of novelty paradigm were used to determine the nature and limitations of these abilities in rhesus monkeys. Socially-housed monkeys at two facilities (UMASS Primate Laboratory and the New England Regional Primate Research Center) were exposed to novelty detection tasks using a vertical object grid arranged on a mesh wall of the animals' pens. Monkeys rapidly responded with increased exploration to the replacement of one familiar object with a novel object, to the movement of a familiar object to a novel location, and to the swapping of two familiar objects. However, novelty of object was more salient than novelty of place. In these initial studies, monkeys were given continuous access to the grid, and only one or two changes occurred on a given day. In subsequent studies, the task difficulty was varied either by reducing the length of grid exposure or increasing the number of changed objects/session. Surprisingly, only a reduction in length of exposure markedly affected novelty detecting abilities. Rhesus monkeys clearly possessed the dual novelty detecting abilities. These skills were negatively affected only when monkeys' access to the grid was limited. The procedure employed here provided a convenient way to assess complex cognitive abilities in a group setting. It also relied on rhesus monkeys' inherent attraction to novelty and required only their species-typical behavior for assessment. PMID- 9973267 TI - Geographic variation in the calls of wild chimpanzees: a reassessment. AB - Male chimpanzees produce a species-typical call, the pant hoot, to communicate to conspecifics over long-distances. Calls given by males from the well-known Gombe and Mahale populations typically consist of four different phases: an introduction, build-up, climax, and let-down. Recent observations suggest that chimpanzees living in the Kibale National Park, Uganda, consistently give calls that lack a build-up and are thus qualitatively distinguishable acoustically from those made by other East African conspecifics. We analyzed additional recordings from Mahale and Kibale to re-examine geographic variation in chimpanzee calls. Results indicate that males from both sites produce pant hoots containing all four parts of the call. Calls made by chimpanzees from the two populations, however, differ in quantitative acoustic measures. Specifically, males at Kibale initiate their calls with significantly longer elements and build-up over briefer periods at slower rates than individuals from Mahale. Kibale males also deliver acoustically less variable calls than chimpanzees at Mahale. Although climax elements do not differ between populations in any single acoustic feature, discriminant function analysis reveals that acoustic variables can be used in combination to assign calls to the correct population at rates higher than that expected by chance. Ecological factors related to differences in habitat acoustics, the sound environment of the local biota, and body size are likely to account for these observed macrogeographic variations in chimpanzee calls. PMID- 9973268 TI - Social housing and pregnancy outcome in captive pigtailed macaques. AB - We present a retrospective analysis of 30 years of breeding records from a colony of pigtailed macaques at the University of Washington's Regional Primate Research Center, specifically examining the effects on pregnancy outcome of sire presence, presence of other pregnant females, group stability, overall group size, and dam age and parity. Data on 2,040 pregnancies (1,890 live births) of socially housed pigtailed macaques (Macaca nemestrina) were obtained from the Washington Regional Primate Research Center's animal colony records from 1967 to 1996. Our results suggest that the presence of the sire and other pregnant females, fewer moves, and lower parity increases the probability of a viable birth. In viable and nonviable births, gestation length was positively related to contact with the sire and other pregnant females, number of moves, and dam age. Once the effect of gestational age was taken into account, birthweight increased with increasing parity and decreased with dam age. Clinical treatment of the dam decreased as sire presence and group size increased and number of moves decreased. The length of treatment was dependent on the number of moves experienced by the dam, with more moves associated with longer treatments. Sire presence was the single most important factor in nearly all measures of reproductive outcome. PMID- 9973269 TI - Elevated ovarian expression and serum concentration of alpha inhibin in the luteal phase during follicular development in the squirrel monkey (Saimiri boliviensis) compared to the human. AB - The goal of the present investigation was to determine in the squirrel monkey the source and pattern of inhibin, a hormone known to effect reproductive steroid levels via pituitary and ovarian mechanisms. Since this seasonally polyestrous species is known to have elevated serum levels of reproductive steroids compared to other primates, the levels of ovarian alpha subunit mRNA expression and serum total alpha inhibin, estradiol, progesterone, and luteinizing hormone were measured and compared to human levels. Expression of the alpha subunit was robust in monkey luteal tissue compared to expression in human luteal tissue. Squirrel monkey serum inhibin peaked 4 days after the luteinizing hormone surge and correlated with progesterone changes. These luteal serum levels of inhibin were greater than 12 times higher than the human levels yet bio-LH activities were less than in the human during the luteal phase. Inhibin concentrations during the nonbreeding season were generally half the levels measured in the breeding season and undetectable in ovariectomized animals. However, exogenous FSH stimulation induced a marked rise in inhibin, which correlated with an estradiol rise. In conclusion, abundant alpha inhibin subunit expression in the luteal ovary of the squirrel monkey and loss of serum delectability in ovariectomized animals indicates that the principle source of inhibin in the squirrel monkey is the ovary. Elevated serum inhibin levels during the luteal phase concurrent with ovulatory-size follicular development is unique among species studied thus far. Possible simultaneous inhibin production from both follicular and luteal tissue may be responsible for the exceptionally high inhibin levels. PMID- 9973270 TI - Protein fate in neurodegenerative proteinopathies: polyglutamine diseases join the (mis)fold. PMID- 9973271 TI - Biological implications of the DNA structures associated with disease-causing triplet repeats. PMID- 9973272 TI - Fragile sites-cytogenetic similarity with molecular diversity. PMID- 9973273 TI - Myotonic dystrophy: the role of RNA CUG triplet repeats. PMID- 9973275 TI - Overgrowth syndromes and the regulation of signaling complexes by proteoglycans. PMID- 9973274 TI - The yeast connection to Friedreich ataxia. PMID- 9973276 TI - Inherited colorectal polyposis and cancer risk of the APC I1307K polymorphism. AB - Germ-line and somatic truncating mutations of the APC gene are thought to initiate colorectal tumor formation in familial adenomatous polyposis syndrome and sporadic colorectal carcinogenesis, respectively. Recently, an isoleucine- >lysine polymorphism at codon 1307 (I1307K) of the APC gene has been identified in 6%-7% of the Ashkenazi Jewish population. To assess the risk of this common APC allelic variant in colorectal carcinogenesis, we have analyzed a large cohort of unselected Ashkenazi Jewish subjects with adenomatous polyps and.or colorectal cancer, for the APC I1307K polymorphism. The APC I1307K allele was identified in 48 (10.1%) of 476 patients. Compared with the frequency in two separate population control groups, the APC I1307K allele is associated with an estimated relative risk of 1.5-1.7 for colorectal neoplasia (both P=.01). Furthermore, compared with noncarriers, APC I1307K carriers had increased numbers of adenomas and colorectal cancers per patient (P=.03), as well as a younger age at diagnosis. We conclude that the APC I1307K variant leads to increased adenoma formation and directly contributes to 3%-4% of all Ashkenazi Jewish colorectal cancer. The estimated relative risk for carriers may justify specific clinical screening for the 360,000 Americans expected to harbor this allele, and genetic testing in the setting of long-term-outcome studies may impact significantly on colorectal cancer prevention in this population. PMID- 9973277 TI - Molecular mechanism of angelman syndrome in two large families involves an imprinting mutation. AB - Patients with Angelman syndrome (AS) and Prader-Willi syndrome with mutations in the imprinting process have biparental inheritance but uniparental DNA methylation and gene expression throughout band 15q11-q13. In several of these patients, microdeletions upstream of the SNRPN gene have been identified, defining an imprinting center (IC) that has been hypothesized to control the imprint switch process in the female and male germlines. We have now identified two large families (AS-O and AS-F) segregating an AS imprinting mutation, including one family originally described in the first genetic linkage of AS to 15q11-q13. This demonstrates that this original linkage is for the 15q11-q13 IC. Affected patients in the AS families have either a 5.5- or a 15-kb microdeletion, one of which narrowed the shortest region of deletion overlap to 1.15 kb in all eight cases. This small region defines a component of the IC involved in AS (ie., the paternal-to-maternal switch element). The presence of an inherited imprinting mutation in multiple unaffected members of these two families, who are at risk for transmitting the mutation to affected children or children of their daughters, raises important genetic counseling issues. PMID- 9973278 TI - Imprinting-mutation mechanisms in Prader-Willi syndrome. AB - Microdeletions of a region termed the "imprinting center" (IC) in chromosome 15q11-q13 have been identified in several families with Prader-Willi syndrome (PWS) or Angelman syndrome who show epigenetic inheritance for this region that is consistent with a mutation in the imprinting process. The IC controls resetting of parental imprints in 15q11-q13 during gametogenesis. We have identified a larger series of cases of familial PWS, including one case with a deletion of only 7.5 kb, that narrows the PWS critical region to <4. 3 kb spanning the SNRPN gene CpG island and exon 1. Identification of a strong DNase I hypersensitive site, specific for the paternal allele, and six evolutionarily conserved (human-mouse) sequences that are potential transcription-factor binding sites is consistent with this region defining the SNRPN gene promoter. These findings suggest that promoter elements at SNRPN play a key role in the initiation of imprint switching during spermatogenesis. We also identified three patients with sporadic PWS who have an imprinting mutation (IM) and no detectable mutation in the IC. An inherited 15q11-q13 mutation or a trans-factor gene mutation are unlikely; thus, the disease in these patients may arise from a developmental or stochastic failure to switch the maternal-to-paternal imprint during parental spermatogenesis. These studies allow a better understanding of a novel mechanism of human disease, since the epigenetic effect of an IM in the parental germ line determines the phenotypic effect in the patient. PMID- 9973279 TI - High prevalence of mutations in the microtubule-associated protein tau in a population study of frontotemporal dementia in the Netherlands. AB - Mutations in microtubule-associated protein tau recently have been identified in familial cases of frontotemporal dementia (FTD). We report the frequency of tau mutations in a large population-based study of FTD carried out in the Netherlands from January 1994 to June 1998. Thirty-seven patients had >/=1 first-degree relative with dementia. A mutation in the tau gene was found in 17.8% of the group of patients with FTD and in 43% of patients with FTD who also had a positive family history of FTD. Three distinct missense mutations (G272V, P301L, R406W) accounted for 15.6% of the mutations. These three missense mutations, and a single amino acid deletion (DeltaK280) that was detected in one patient, strongly reduce the ability of tau to promote microtubule assembly. We also found an intronic mutation at position +33 after exon 9, which is likely to affect the alternative splicing of tau. Tau mutations are responsible for a large proportion of familial FTD cases; however, there are also families with FTD in which no mutations in tau have been found, which indicates locus and/or allelic heterogeneity. The different tau mutations may result in disturbances in the interactions of the protein tau with microtubules, resulting in hyperphosphorylation of tau protein, assembly into filaments, and subsequent cell death. PMID- 9973280 TI - Genotype/Phenotype analysis of a photoreceptor-specific ATP-binding cassette transporter gene, ABCR, in Stargardt disease. AB - Mutation scanning and direct DNA sequencing of all 50 exons of ABCR were completed for 150 families segregating recessive Stargardt disease (STGD1). ABCR variations were identified in 173 (57%) disease chromosomes, the majority of which represent missense amino acid substitutions. These ABCR variants were not found in 220 unaffected control individuals (440 chromosomes) but do cosegregate with the disease in these families with STGD1, and many occur in conserved functional domains. Missense amino acid substitutions located in the amino terminal one-third of the protein appear to be associated with earlier onset of the disease and may represent misfolding alleles. The two most common mutant alleles, G1961E and A1038V, each identified in 16 of 173 disease chromosomes, composed 18.5% of mutations identified. G1961E has been associated previously, at a statistically significant level in the heterozygous state, with age-related macular degeneration (AMD). Clinical evaluation of these 150 families with STGD1 revealed a high frequency of AMD in first- and second-degree relatives. These findings support the hypothesis that compound heterozygous ABCR mutations are responsible for STGD1 and that some heterozygous ABCR mutations may enhance susceptibility to AMD. PMID- 9973281 TI - Molecular analysis of SALL1 mutations in Townes-Brocks syndrome. AB - Townes-Brocks syndrome (TBS) is an autosomal dominantly inherited malformation syndrome characterized by anal, renal, limb, and ear anomalies. Recently, we showed that mutations in the putative zinc finger transcription factor gene SALL1 cause TBS. To determine the spectrum of SALL1 mutations and to investigate the genotype-phenotype correlations in TBS, we examined 23 additional families with TBS or similar phenotypes for SALL1 mutations. In 9 of these families mutations were identified. None of the mutations has previously been described. Two of these mutations are nonsense mutations, one of which occurred in three unrelated families. Five of the mutations are short deletions. All of the mutations are located 5' of the first double zinc finger (DZF) encoding region and are therefore predicted to result in putative prematurely terminated proteins lacking all DZF domains. This suggests that only SALL1 mutations that remove the DZF domains result in TBS. We also present evidence that in rare cases SALL1 mutations can lead to phenotypes similar to Goldenhar syndrome. However, phenotypic differences in TBS do not seem to depend on the site of mutation. PMID- 9973282 TI - De novo alu-element insertions in FGFR2 identify a distinct pathological basis for Apert syndrome. AB - Apert syndrome, one of five craniosynostosis syndromes caused by allelic mutations of fibroblast growth-factor receptor 2 (FGFR2), is characterized by symmetrical bony syndactyly of the hands and feet. We have analyzed 260 unrelated patients, all but 2 of whom have missense mutations in exon 7, which affect a dipeptide in the linker region between the second and third immunoglobulin-like domains. Hence, the molecular mechanism of Apert syndrome is exquisitely specific. FGFR2 mutations in the remaining two patients are distinct in position and nature. Surprisingly, each patient harbors an Alu-element insertion of approximately 360 bp, in one case just upstream of exon 9 and in the other case within exon 9 itself. The insertions are likely to be pathological, because they have arisen de novo; in both cases this occurred on the paternal chromosome. FGFR2 is present in alternatively spliced isoforms characterized by either the IIIb (exon 8) or IIIc (exon 9) domains (keratinocyte growth-factor receptor [KGFR] and bacterially expressed kinase, respectively), which are differentially expressed in mouse limbs on embryonic day 13. Splicing of exon 9 was examined in RNA extracted from fibroblasts and keratinocytes from one patient with an Alu insertion and two patients with Pfeiffer syndrome who had nucleotide substitutions of the exon 9 acceptor splice site. Ectopic expression of KGFR in the fibroblast lines correlated with the severity of limb abnormalities. This provides the first genetic evidence that signaling through KGFR causes syndactyly in Apert syndrome. PMID- 9973283 TI - Identification and characterization of a mutation, in the human UDP-galactose-4 epimerase gene, associated with generalized epimerase-deficiency galactosemia. AB - Epimerase-deficiency galactosemia results from impairment of the human enzyme UDP galactose-4-epimerase (hGALE). We and others have identified substitution mutations in the hGALE alleles of patients with the clinically mild, peripheral form of epimerase deficiency. We report here the first identification of an hGALE mutation in a patient with the clinically severe, generalized form of epimerase deficiency. The mutation, V94M, was found on both GALE alleles of this patient. This same mutation also was found in the homozygous state in two additional patients with generalized epimerase deficiency. The specific activity of the V94M hGALE protein expressed in yeast was severely reduced with regard to UDP galactose and partially reduced with regard to UDP-N-acetylgalactosamine. In contrast, two GALE-variant proteins associated with peripheral epimerase deficiency, L313M-hGALE and D103G-hGALE, demonstrated near-normal levels of activity with regard to both substrates, but a third allele, G90E-hGALE, demonstrated little, if any, detectable activity, despite near-normal abundance. G90E originally was identified in a heterozygous patient whose other allele remains uncharacterized. Thermal lability and protease-sensitivity studies demonstrated compromised stability in all of the partially active mutant enzymes. PMID- 9973284 TI - DNA rearrangements on both homologues of chromosome 17 in a mildly delayed individual with a family history of autosomal dominant carpal tunnel syndrome. AB - Disorders known to be caused by molecular and cytogenetic abnormalities of the proximal short arm of chromosome 17 include Charcot-Marie-Tooth disease type 1A (CMT1A), hereditary neuropathy with liability to pressure palsies (HNPP), Smith Magenis syndrome (SMS), and mental retardation and congenital anomalies associated with partial duplication of 17p. We identified a patient with multifocal mononeuropathies and mild distal neuropathy, growth hormone deficiency, and mild mental retardation who was found to have a duplication of the SMS region of 17p11.2 and a deletion of the peripheral myelin protein 22 (PMP22) gene within 17p12 on the homologous chromosome. Further molecular analyses reveal that the dup(17)(p11.2p11.2) is a de novo event but that the PMP22 deletion is familial. The family members with deletions of PMP22 have abnormalities indicative of carpal tunnel syndrome, documented by electrophysiological studies prior to molecular analysis. The chromosomal duplication was shown by interphase FISH analysis to be a tandem duplication. These data indicate that familial entrapment neuropathies, such as carpal tunnel syndrome and focal ulnar neuropathy syndrome, can occur because of deletions of the PMP22 gene. The co-occurrence of the 17p11.2 duplication and the PMP22 deletion in this patient likely reflects the relatively high frequency at which these abnormalities arise and the underlying molecular characteristics of the genome in this region. PMID- 9973285 TI - Clear correlation of genotype with disease phenotype in very-long-chain acyl-CoA dehydrogenase deficiency. AB - Very-long-chain acyl-CoA dehydrogenase (VLCAD) catalyzes the initial rate limiting step in mitochondrial fatty acid beta-oxidation. VLCAD deficiency is clinically heterogenous, with three major phenotypes: a severe childhood form, with early onset, high mortality, and high incidence of cardiomyopathy; a milder childhood form, with later onset, usually with hypoketotic hypoglycemia as the main presenting feature, low mortality, and rare cardiomyopathy; and an adult form, with isolated skeletal muscle involvement, rhabdomyolysis, and myoglobinuria, usually triggered by exercise or fasting. To examine whether these different phenotypes are due to differences in the VLCAD genotype, we investigated 58 different mutations in 55 unrelated patients representing all known clinical phenotypes and correlated the mutation type with the clinical phenotype. Our results show a clear relationship between the nature of the mutation and the severity of disease. Patients with the severe childhood phenotype have mutations that result in no residual enzyme activity, whereas patients with the milder childhood and adult phenotypes have mutations that may result in residual enzyme activity. This clear genotype-phenotype relationship is in sharp contrast to what has been observed in medium-chain acyl-CoA dehydrogenase deficiency, in which no correlation between genotype and phenotype can be established. PMID- 9973286 TI - Prevalence and phenotype consequence of FRAXA and FRAXE alleles in a large, ethnically diverse, special education-needs population. AB - We conducted a large population-based survey of fragile X (FRAXA) syndrome in ethnically diverse metropolitan Atlanta. The eligible study population consisted of public school children, aged 7-10 years, in special education-needs (SEN) classes. The purpose of the study was to estimate the prevalence among whites and, for the first time, African Americans, among a non-clinically referred population. At present, 5 males with FRAXA syndrome (4 whites and 1 African American), among 1,979 tested males, and no females, among 872 tested females, were identified. All males with FRAXA syndrome were mentally retarded and had been diagnosed previously. The prevalence for FRAXA syndrome was estimated to be 1/3,460 (confidence interval [CI] 1/7,143-1/1,742) for the general white male population and 1/4, 048 (CI 1/16,260-1/1,244) for the general African American male population. We also compared the frequency of intermediate and premutation FRAXA alleles (41-199 repeats) and fragile XE syndrome alleles (31-199 repeats) in the SEN population with that in a control population, to determine if there was a possible phenotype consequence of such high-repeat alleles, as has been reported previously. No difference was observed between our case and control populations, and no difference was observed between populations when the probands were grouped by a rough estimate of IQ based on class placement. These results suggest that there is no phenotype consequence of larger alleles that would cause carriers to be placed in an SEN class. PMID- 9973287 TI - DNA variation in a 5-Mb region of the X chromosome and estimates of sex specific/type-specific mutation rates. AB - We describe a new approach for the study of human genome variation, based on our solid-phase fluorescence chemical mismatch-cleavage method. Multiplex screening rates >/=80 kb/36-lane gels are achieved, and accuracy of mismatch location is within +/-2 bp. The density of differences between DNA from any two humans is sufficiently low, and the estimate of their position is accurate enough, to avoid sequencing of most polymorphic sites when defining their allelic state. Furthermore, highly variable sequences, such as microsatellites, are distinguished easily, so that separate consideration can be given to loci that do and do not fit the definition of infinite mutation sites. We examined a 5-Mb region of Xq22 to define the haplotypes of 23 men (9 Europeans, 9 Ashkenazim, and 5 Pygmies) by reference to DNA from one Italian man. Fifty-eight 1.5-kb segments revealed 102 segregating sites. Seven of these are shared by all three groups, two by Pygmies and Europeans, two by Pygmies and Ashkenazim, and 19 by Ashkenazim and Europeans. Europeans are the least polymorphic, and Pygmies are the most polymorphic. Conserved allelic associations were recognizable within 40-kb DNA segments, and so was recombination in the longer intervals separating such segments. The men showed only three segregating sites in a 16.5-kb unique region of the Y chromosome. Divergence between X- and Y-chromosome sequences of humans and chimpanzees indicated higher male mutation rates for different types of mutations. These rates for the X chromosomes were very similar to those estimated for the X-linked factor IX gene in the U.K. population. PMID- 9973288 TI - Hyperparathyroidism-jaw tumor syndrome: the HRPT2 locus is within a 0.7-cM region on chromosome 1q. AB - Hyperparathyroidism-jaw tumor syndrome (HPT-JT) is an autosomal dominant disease characterized by the development of multiple parathyroid adenomas and multiple fibro-osseous tumors of the maxilla and mandible. Some families have had affected members with involvement of the kidneys, variously reported as Wilms tumors, nephroblastomas, and hamartomas. The HPT-JT gene (HRPT2) maps to chromosome 1q25 q31. We describe further investigation of two HPT-JT families (K3304 and K3349) identified through the literature. These two expanded families and two previously reported families were investigated jointly for linkage with 21 new, closely linked markers. Multipoint linkage analysis resulted in a maximum LOD score of 7.83 (at recombination fraction 0) for markers D1S2848-D1S191. Recombination events in these families reduced the HRPT2 region to approximately 14.7 cM. In addition, two of these four study families (i.e., K3304 and K11687) share a 2.2 cM length of their (expanded) affected haplotype, indicating a possible common origin. Combining the linkage data and shared-haplotype data, we propose a 0.7-cM candidate region for HRPT2. PMID- 9973289 TI - A gene for autosomal recessive symmetrical spastic cerebral palsy maps to chromosome 2q24-25. AB - Cerebral palsy has an incidence of approximately 1/500 births, although this varies between different ethnic groups. Genetic forms of the disease account for approximately 1%-2% of cases in most countries but contribute a larger proportion in populations with extensive inbreeding. We have clinically characterized consanguineous families with multiple children affected by symmetrical spastic cerebral palsy, to locate recessive genes responsible for this condition. The eight families studied were identified from databases of patients in different regions of the United Kingdom. After ascertainment and clinical assessment, we performed a genomewide search for linkage, using 290 polymorphic DNA markers. In three families, a region of homozygosity at chromosome 2q24-q25 was identified between the markers D2S124 and D2S148. The largest family gave a maximum LOD score of 3.0, by multipoint analysis (HOMOZ). The maximum combined multipoint LOD score for the three families was 5.75. The minimum region of homozygosity is approximately 5 cM between the markers D2S124 and D2S2284. We have shown that a proportion of autosomal recessive symmetrical spastic cerebral palsy maps to chromosome 2q24-25. The identification of genes involved in the etiology of cerebral palsy may lead to improved management of this clinically intractable condition. PMID- 9973290 TI - Mapping of a familial moyamoya disease gene to chromosome 3p24.2-p26. AB - Moyamoya disease is characterized by bilateral stenosis and/or occlusion of the terminal portion of the internal carotid artery. Moyamoya disease is prevalent among patients <10 years of age. Although most cases appear to be sporadic, approximately 10% occur as familial cases. The incidence of familial cases has been increasing because noninvasive diagnostic equipment, such as magnetic resonance imaging and magnetic-resonance angiography, can detect the disease in almost all affected patients, including asymptomatic patients, during screening studies. In this study, we performed a total genome search to identify the location of a familial moyamoya disease gene in 16 families, assuming an unknown mode of inheritance. A linkage was found between the disease and markers located at 3p24.2-26. A maximum NPL score of 3.46 was obtained with marker D3S3050. This is the first genetic locus found to be involved in the molecular pathogenesis of familial moyamoya disease. PMID- 9973291 TI - Limb mammary syndrome: a new genetic disorder with mammary hypoplasia, ectrodactyly, and other Hand/Foot anomalies maps to human chromosome 3q27. AB - We report on a large Dutch family with a syndrome characterized by severe hand and/or foot anomalies, and hypoplasia/aplasia of the mammary gland and nipple. Less frequent findings include lacrimal-duct atresia, nail dysplasia, hypohydrosis, hypodontia, and cleft palate with or without bifid uvula. This combination of symptoms has not been reported previously, although there is overlap with the ulnar mammary syndrome (UMS) and with ectrodactyly, ectodermal dysplasia, and clefting syndrome. Allelism with UMS and other related syndromes was excluded by linkage studies with markers from the relevant chromosomal regions. A genomewide screening with polymorphic markers allowed the localization of the genetic defect to the subtelomeric region of chromosome 3q. Haplotype analysis reduced the critical region to a 3-cM interval of chromosome 3q27. This chromosomal segment has not been implicated previously in disorders with defective development of limbs and/or mammary tissue. Therefore, we propose to call this apparently new disorder "limb mammary syndrome" (LMS). The SOX2 gene at 3q27 might be considered an excellent candidate gene for LMS because the corresponding protein stimulates expression of FGF4, an important signaling molecule during limb outgrowth and development. However, no mutations were found in the SOX2 open reading frame, thus excluding its involvement in LMS. PMID- 9973292 TI - Mapping of primary congenital lymphedema to the 5q35.3 region. AB - Primary lymphedema is a chronic tissue swelling, most frequently of the lower limbs, resulting from deficient lymphatic drainage. The variability of the affected phenotype, incomplete penetrance, lack of large families, and possible genetic heterogeneity have hampered the identification of causative genes until now. We carried out a genomewide search, using a four-generation North American family with dominantly inherited primary congenital lymphedema (PCL), otherwise known as "Milroy disease," or "hereditary lymphedema type I" (MIM 153100). Linkage to markers from the 5q35.3 region in this and four additional, British families was established. A minimum of 79 directly scorable haplotypes (37 affected) in five families conspicuously segregated with the most telomeric region of 5q35.3, thus suggesting a major locus for PCL in this vicinity. No recombination was observed with D5S408 (Z = 10.03) and D5S2006 (Z = 8.46) with a combined multipoint score of 16.55. While D5S2073 and WIAF-2213 defined the upper centromeric boundary, no recombinants were obtained for the last telomeric marker of D5S2006. Four unaffected subjects were identified as gene carriers and provided an estimated penetrance ratio of.84 for this condition. A few of the positionally mapped genes in the 5q35 region that may potentially be involved in the etiology of this condition are CANX, FGFR4, HK3, and hnRPH1. PMID- 9973293 TI - Identification of a new autosomal dominant limb-girdle muscular dystrophy locus on chromosome 7. AB - We report the identification of a new locus for autosomal dominant limb-girdle muscular dystrophy (LGMD1) on 7q. Two of five families (1047 and 1701) demonstrate evidence in favor of linkage to this region. The maximum two-point LOD score for family 1047 was 3.76 for D7S427, and that for family 1701 was 2.63 for D7S3058. Flanking markers place the LGMD1 locus between D7S2423 and D7S427, with multipoint analysis slightly favoring the 9-cM interval spanned by D7S2546 and D7S2423. Three of five families appear to be unlinked to this new locus on chromosome 7, thus establishing further heterogeneity within the LGMD1 diagnostic classification. PMID- 9973294 TI - Novel locus for autosomal dominant hereditary spastic paraplegia, on chromosome 8q. AB - Hereditary spastic paraplegia (HSP) is a clinically and genetically heterogeneous group of disorders characterized by insidiously progressive spastic weakness in the legs. Genetic loci for autosomal dominant HSP exist on chromosomes 2p, 14q, and 15q. These loci are excluded in 45% of autosomal dominant HSP kindreds, indicating the presence of additional loci for autosomal dominant HSP. We analyzed a Caucasian kindred with autosomal dominant HSP and identified tight linkage between the disorder and microsatellite markers on chromosome 8q (maximum two-point LOD score 5.51 at recombination fraction 0). Our results clearly establish the existence of a locus for autosomal dominant HSP on chromosome 8q23 24. Currently this locus spans 6.2 cM between D8S1804 and D8S1774 and includes several potential candidate genes. Identifying this novel HSP locus on chromosome 8q23-24 will facilitate discovery of this HSP gene, improve genetic counseling for families with linkage to this locus, and extend our ability to correlate clinical features with different HSP loci. PMID- 9973295 TI - Brachydactyly type B: clinical description, genetic mapping to chromosome 9q, and evidence for a shared ancestral mutation. AB - Autosomal dominant brachydactyly type B (BDB) is characterized by nail aplasia with rudimentary or absent distal and middle phalanges. We describe two unrelated families with BDB. One family is English; the other family is Canadian but of English ancestry. We assigned the BDB locus in the Canadian family to an 18-cM interval on 9q, using linkage analysis (LOD score 3.5 at recombination fraction [theta] 0, for marker D9S938). Markers across this interval also cosegregated with the BDB phenotype in the English family (LOD score 2.1 at straight theta=0, for marker D9S277). Within this defined interval is a smaller (7.5-cM) region that contains 10 contiguous markers whose disease-associated haplotype is shared by the two families. This latter result suggests a common founder among families of English descent that are affected with BDB. PMID- 9973296 TI - Brachydactyly type B: linkage to chromosome 9q22 and evidence for genetic heterogeneity. AB - Brachydactyly type B (BDB), an autosomal dominant disorder, is the most severe of the brachydactylies and is characterized by hypoplasia or absence of the terminal portions of the index to little fingers, usually with absence of the nails. The thumbs may be of normal length but are often flattened and occasionally are bifid. The feet are similarly but less severely affected. We have performed a genomewide linkage analysis of three families with BDB, two English and one Portugese. The two English families show linkage to the same region on chromosome 9 (combined multipoint maximum LOD score 8.69 with marker D9S257). The 16-cM disease interval is defined by recombinations with markers D9S1680 and D9S1786. These two families share an identical disease haplotype over 18 markers, inclusive of D9S278-D9S280. This provides strong evidence that the English families have the same ancestral mutation, which reduces the disease interval to <12.7 cM between markers D9S257 and D9S1851 in chromosome band 9q22. In the Portuguese family, we excluded linkage to this region, a result indicating that BDB is genetically heterogeneous. Reflecting this, there were atypical clinical features in this family, with shortening of the thumbs and absence or hypoplasia of the nails of the thumb and hallux. These results enable a refined classification of BDB and identify a novel locus for digit morphogenesis in 9q22. PMID- 9973297 TI - Genetic mapping to 10q23.3-q24.2, in a large Italian pedigree, of a new syndrome showing bilateral cataracts, gastroesophageal reflux, and spastic paraparesis with amyotrophy. AB - We have recently observed a large pedigree with a new rare autosomal dominant spastic paraparesis. In three subsequent generations, 13 affected individuals presented with bilateral cataracts, gastroesophageal reflux with persistent vomiting, and spastic paraparesis with amyotrophy. Bilateral cataracts occurred in all affected individuals, with the exception of one patient who presented with a chorioretinal dystrophy, whereas clinical signs of spastic paraparesis showed a variable expressivity. Using a genomewide mapping approach, we mapped the disorder to the long arm of chromosome 10 on band q23.3-q24.2, in a 12-cM chromosomal region where additional neurologic disorders have been localized. The spectrum of phenotypic manifestations in this family is reminiscent of a smaller pedigree, reported recently, confirming the possibility of a new syndrome. Finally, the anticipation of symptoms suggests that an unstable trinucleotide repeat may be responsible for the condition. PMID- 9973298 TI - Mapping of a new autosomal dominant spinocerebellar ataxia to chromosome 22. AB - The autosomal dominant cerebellar ataxias (ADCAs) are a clinically and genetically heterogeneous group of disorders. The clinical symptoms include cerebellar dysfunction and associated signs from dysfunction in other parts of the nervous system. So far, five spinocerebellar ataxia (SCA) genes have been identified: SCA1, SCA2, SCA3, SCA6, and SCA7. Loci for SCA4 and SCA5 have been mapped. However, approximately one-third of SCAs have remained unassigned. We have identified a Mexican American pedigree that segregates a new form of ataxia clinically characterized by gait and limb ataxia, dysarthria, and nystagmus. Two individuals have seizures. After excluding all known genetic loci for linkage, we performed a genomewide search and identified linkage to a 15-cM region on chromosome 22q13. A maximum LOD score of 4.3 (recombination fraction 0) was obtained for D22S928 and D22S1161. This distinct form of ataxia has been designated "SCA10." Anticipation was observed in the available parent-child pairs, suggesting that trinucleotide-repeat expansion may be the mutagenic mechanism. PMID- 9973299 TI - Congenital motor nystagmus linked to Xq26-q27. AB - Congenital motor nystagmus (CMN) is a hereditary disorder characterized by bilateral ocular oscillations that begin in the first 6 mo of life. It must be distinguished from those genetic disorders-such as ocular albinism (OA), congenital stationary night blindness (CSNB), and blue-cone monochromatism (BCM) in which nystagmus accompanies a clinically apparent defect in the visual sensory system. Although CMN is presumed to arise from a neurological abnormality of fixation, it is not known whether the molecular defect is located in the eye or in the brain. It may be inherited in an autosomal dominant, autosomal recessive, or X-linked pattern. Three families with CMN inherited in an X-linked, irregularly dominant pattern were investigated with linkage and candidate gene analysis. The penetrance among obligate female carriers was 54%. Evaluation of markers in the region of the genes for X-linked OA, CSNB, and BCM revealed no evidence of linkage, supporting the hypothesis that CMN represents a distinct entity. The gene was mapped to chromosome Xq26-q27 with the following markers: GATA172D05 (LOD score 3.164; recombination fraction [theta] = 0.156), DXS1047 (LOD score 10.296; theta = 0), DXS1192 (LOD score 8.174; theta = 0.027), DXS1232 (LOD score 6.015; theta = 0.036), DXS984 (LOD score 6.695; theta = 0), and GATA31E08 (LOD score 4.940; theta = 0.083). Assessment of haplotypes and multipoint linkage analysis, which gave a maximum LOD score of 10.790 with the 1 LOD-unit support interval spanning approximately 7 cM, place the gene in a region between GATA172D05 and DXS1192. Evaluation of candidate genes CDR1 and SOX3 did not reveal mutations in affected male subjects. PMID- 9973301 TI - The central Siberian origin for native American Y chromosomes. AB - Y chromosomal DNA polymorphisms were used to investigate Pleistocene male migrations to the American continent. In a worldwide sample of 306 men, we obtained 32 haplotypes constructed with the variation found in 30 distinct polymorphic sites. The major Y haplotype present in most Native Americans was traced back to recent ancestors common with Siberians, namely, the Kets and Altaians from the Yenissey River Basin and Altai Mountains, respectively. Going further back, the next common ancestor gave rise also to Caucasoid Y chromosomes, probably from the central Eurasian region. This study, therefore, suggests a predominantly central Siberian origin for Native American paternal lineages for those who could have migrated to the Americas during the Upper Pleistocene. PMID- 9973302 TI - Comparison of the power and accuracy of biallelic and microsatellite markers in population-based gene-mapping methods. AB - Because of their great abundance and amenability to fully automated genotyping, single-nucleotide polymorphisms (SNPs) and simple insertion/deletion are emerging as a new generation of markers for positional cloning. Although the efficiency and cost associated with the markers are important in the mapping of human disease genes, the power to detect the linkage between the marker and the disease locus, as well as the accuracy of the estimation of the map location of the disease gene, dictate the selection of the markers. Both the power and the accuracy depend not only on the type of the markers but also on other factors, such as the age of the disease mutation, the magnitude of the genetic effect, the marker-allele distribution in the population, mutation rates of marker loci, the frequency of the disease allele, the recombination fraction, and the methods for mapping the human disease genes. In this article, we develop a mathematical framework and the analytical formulas for calculation of the power and the accuracy and investigate the impact that the aforementioned factors have on the power and the accuracy, by using two population-based gene-mapping methods likelihood-based linkage-disequilibrium mapping and the transmission/disequilibrium test, for both biallelic SNPs and microsatellites. These studies provide not only guidance in selection of the markers and in the design of the sample scheme for positional cloning but also insight into the biological bases of the mapping of human disease genes. PMID- 9973300 TI - Linkage of low-density lipoprotein size to the lipoprotein lipase gene in heterozygous lipoprotein lipase deficiency. AB - Small low-density lipoprotein (LDL) particles are a genetically influenced coronary disease risk factor. Lipoprotein lipase (LpL) is a rate-limiting enzyme in the formation of LDL particles. The current study examined genetic linkage of LDL particle size to the LpL gene in five families with structural mutations in the LpL gene. LDL particle size was smaller among the heterozygous subjects, compared with controls. Among heterozygous subjects, 44% were classified as affected by LDL subclass phenotype B, compared with 8% of normal family members. Plasma triglyceride levels were significantly higher, and high-density lipoprotein cholesterol (HDL-C) levels were lower, in heterozygous subjects, compared with normal subjects, after age and sex adjustment. A highly significant LOD score of 6.24 at straight theta=0 was obtained for linkage of LDL particle size to the LpL gene, after adjustment of LDL particle size for within-genotype variance resulting from triglyceride and HDL-C. Failure to adjust for this variance led to only a modest positive LOD score of 1.54 at straight theta=0. Classifying small LDL particles as a qualitative trait (LDL subclass phenotype B) provided only suggestive evidence for linkage to the LpL gene (LOD=1. 65 at straight theta=0). Thus, use of the quantitative trait adjusted for within genotype variance, resulting from physiologic covariates, was crucial for detection of significant evidence of linkage in this study. These results indicate that heterozygous LpL deficiency may be one cause of small LDL particles and may provide a potential mechanism for the increase in coronary disease seen in heterozygous LpL deficiency. This study also demonstrates a successful strategy of genotypic specific adjustment of complex traits in mapping a quantitative trait locus. PMID- 9973303 TI - Power of association and linkage tests when the disease alleles are unobserved. AB - Genomewide association studies have been advocated as a promising alternative to genomewide linkage scans for detection of small-effect genes in complex diseases. Comparisons of power and sample size between the two strategies have shown considerable advantages for the association studies. These comparisons assume that the set of markers includes the exact disease-related polymorphism. A concern, however, is that the power of an association study decreases when this is not the case, because of discrepant allele frequencies and less-than-maximum disequilibrium between the disease-related polymorphism and its nearest marker. Here, we quantify this concern by comparing the sample sizes needed by the two strategies when the markers exclude the disease-related polymorphism. For affected sib pairs and their parents, we found that incomplete disequilibrium and differing allele frequencies can have substantial negative impact on the power of association studies, resulting, in some circumstances, in little gain and even in loss of power, compared with linkage analysis. We provide some guidelines for choosing between strategies, for the detection of genes for complex diseases. PMID- 9973304 TI - Both recessive and dominant forms of anhidrotic/hypohidrotic ectodermal dysplasia map to chromosome 2q11-q13. PMID- 9973305 TI - Mosaicism and sporadic familial adenomatous polyposis. PMID- 9973306 TI - HPS gene mutations in Hermansky-Pudlak syndrome. PMID- 9973307 TI - RB1 gene mutations in peripheral blood DNA of patients with isolated unilateral retinoblastoma. PMID- 9973308 TI - TDT clarification. PMID- 9973309 TI - Role of iron in anthracycline cardiotoxicity: new tunes for an old song? AB - The clinical use of anticancer anthracyclines is limited by the development of a distinctive and life-threatening form of cardiomyopathy upon chronic treatment. Commonly accepted mechanistic hypotheses have assigned a pivotal role to iron, which would act as a catalyst for free radical reactions and oxidative stress. Although perhaps involved in acute aspects of anthracycline cardiotoxicity, the role of free radical-based mechanisms in long-term effects has been challenged on both experimental and clinical grounds, and alternative hypotheses independent of iron and free radicals have flourished. More recently, studies of the role of C 13 hydroxy metabolites of anthracyclines have provided new perspectives on the role of iron in the cardiotoxicity of these drugs, showing that such metabolites can impair intracellular iron handling and homeostasis. The present review applies a multisided approach to the critical evaluation of various hypotheses proposed over the last decade for the role of iron in anthracycline-induced cardiotoxicity. The main goal of the authors is to build a unifying pattern that would both account for hitherto unexplained experimental observations and help design novel and more rational strategies toward a much-needed improvement in the therapeutic index of anthracyclines. PMID- 9973310 TI - Evolving ideas about osmosis and capillary fluid exchange. AB - When a solute is dissolved in water at (T, pel), the temperature and external pressure applied to the solution, the water in the solution is altered as is pure liquid water at (T, pel - piH2Ol). The liquid water and the water in the solution are in equilibrium when piH2Ol is the osmotic pressure of the water in the solution. Every partial molar property of the water in the solution at (T, pel), including its vapor pressure, chemical potential, volume, internal energy, enthalpy and entropy, is identical with the same molar property of pure liquid water at (T, pel - piH2Ol). This elementary fact was deduced by Hulett in 1903 from a thought experiment; he concluded that the internal tension in the force bonding the water is the same in both solution and pure liquid water, in equilibrium, at these differing applied pressures. Hulett's understanding of osmosis and the means by which the water was altered by the solute were neglected and abandoned. Competing ideas included the notions that the solute attracts the water into the solution and that the solute lowers the activity (or concentration) of the water in the solution. These ideas imply that the solute acts on the solvent at the semipermeable membrane separating the solution and water. Hulett's theory of osmosis requires that the solute alter the water at the free surface of the solution where the solute exerts an internal pressure on the boundary of the solution retaining the solute. Fluid exchange across the capillary endothelium is influenced, in part, by colloidal proteins in the plasma. The role of the proteins in capillary fluid exchange must be reinterpreted based on Hulett's view, the only valid view of osmosis. PMID- 9973311 TI - Glucose and free radicals impair the antioxidant properties of serum albumin. AB - Epidemiological data consistently show that reduced levels of serum albumin, which is the most abundant protein in plasma, are associated with an increased mortality risk. Various biological properties evidenced by direct effects of the albumin molecule may explain its beneficial effects. The present work aimed to investigate in vitro whether glycation or free radicals or both factors would affect the antioxidant properties of bovine serum albumin (BSA). Glycation was performed by long-term incubations (60 days) of BSA with increasing concentrations of glucose (up to 500 mmol/l) at 37 degreesC. Minimally oxidized BSA was obtained after controlled incubations of dialyzed BSA samples with a water-soluble free radical generator [2,2' azo-bis(2-amidinopropane) HCl]. The glycation-mediated modifications and the free radical-induced conformational changes of BSA were monitored using intrinsic fluorescence measurements of the tryptophan residues and acrylamide as a quenching agent. Thiol groups, Amadori glycophore contents, and boronate binding were also measured. We found that the changes observed in the conformation of the BSA molecule were associated with modifications of its antioxidant properties. The latter were studied by the copper-mediated oxidation of human low density lipoproteins and the free radical induced blood hemolysis test. Our data support the concept that oxidative-induced BSA modifications are important determinants in the antioxidant properties of BSA. Glycated BSA still behaved as an antioxidant but became pro-oxidant in the presence of copper, probably by generating oxygenated species. These data confirm the key role of metals ions in this process. Although these results warrant further in vivo investigations, we propose that, considering the poor glucose control found in diabetics as well as the key role of oxidative stress in vascular complications, glycation-mediated and free radical-induced impairment of the antioxidant properties of albumin might be important parameters in vascular complications encountered in diabetes. PMID- 9973312 TI - Synergy between cyclo-oxygenase-2 induction and arachidonic acid supply in vivo: consequences for nonsteroidal antiinflammatory drug efficacy. AB - Prostanoids produced via the action of cyclo-oxygenase-2 (COX-2) appear central to many inflammatory conditions. Here we show in LPS-treated rats, however, that COX-2 induction alone does not greatly increase prostanoid production in vivo. For this, a second, arachidonic acid liberating stimulus is also required. Thus, only after intravenous injection of bradykinin or exogenous arachidonic acid was a marked increase in prostanoid formation seen. There is, therefore, synergy between proinflammatory mediators: both induction of COX-2 protein and an increase in the supply of arachidonic acid are required to greatly enhance prostanoid production. Second, we show that supplying arachidonic acid to increase prostanoid production reduces the effectiveness of both currently used nonsteroidal antiinflammatory drugs (NSAIDs) (diclofenac) and novel COX-2 selective inhibitors (NS-398, celecoxib) as inhibitors of COX-2 activity. Our data lead to two important conclusions. First, increased prostanoid production in inflammation is a two-component response: increased COX-2 expression and increased arachidonic acid supply. Second, the supply of arachidonic acid to COX 2 determines the effectiveness of NSAIDs. NSAIDs and selective COX-2 inhibitors, therefore, will generally be less effective at more inflamed sites, providing a rationale for the very high doses of NSAIDs required in human conditions such as rheumatoid arthritis.--Hamilton, L. C., Tomlinson, A. M., Mitchell, J. A., Warner, T. D. Synergy between cyclo-oxygenase-2 induction and arachidonic acid supply in vivo: consequences for nonsteroidal antiinflammatory drug efficacy. PMID- 9973313 TI - A caspase inhibitor fully protects rats against lethal normothermic liver ischemia by inhibition of liver apoptosis. AB - Apoptosisis activated during the early phase of reperfusion after liver ischemia and after liver transplantation in animals. However, the molecular basis of ischemia-induced cell death remains poorly understood. In this study we show that hepatocytes from ischemic liver lobes undergo apoptosis after reperfusion. In vivo pretreatment of rats with a specific inhibitor of caspases abrogates the apoptotic response in ischemic liver lobes. Inhibition of apoptosis can be accounted for by total inhibition of caspase activation as assessed in an enzymatic assay and by specific affinity labeling. Treatment with a caspase inhibitor fully protects rats from death induced by ischemia/reperfusion. These findings indicate that liver injury after ischemia/reperfusion can be prevented by inhibition of caspases. Thus, caspase inhibitors may have important therapeutic implications in liver ischemic diseases and after liver transplantation. PMID- 9973314 TI - Self-renewal, maturation, and differentiation of the rat myelomonocytic hematopoietic stem cell. AB - Hematopoiesis is viewed as a differentiating system emanating from a pluripotent hematopoietic stem cell capable of both self-renewal and differentiation. By identifying and characterizing a novel and highly specific in vitro mitogenic response to the N-acetyl glucosamyl/sialic acid specific, stem cell-binding lectin wheat germ agglutinin (WGA), we demonstrate the existance of a rare (0.1%), plastic adherent precursor in rat bone marrow capable of proliferation (two to seven divisions) in response to WGA. Stimulated cells possess a lineage (lin)low/- immunophenotype and immature blastoid morphology (WGA blasts). A subsequent proliferative response to stem cell factor (SCF), the ligand for the proto-oncogene receptor tyrosine kinase c-kit, is characterized by an initial maturation in immunophenotype and subsequent self-renewal of cells (SCF blasts) without differentiation for at least 50 generations. Although granulocyte colony stimulating factor (G-CSF), interleukin (IL) -6, IL-7, and IL-11 synergize with SCF to increase blast colony formation, cytokines such as granulocyte-macrophage CSF or IL-3 are without significant effect. At all time points in culture, however, cells rapidly differentiate to mature neutrophils with dexamethasone or to mainly monocytes/macrophages in the presence of 1alpha,25-dihydroxyvitamin D3, characterized by cell morphology and cytochemistry. Removal of SCF during blast maturation, self-renewal, or induction of differentiation phases results in apoptotic cell death. Data indicate a pivotal role for SCF/c-kit interaction during antigenic maturation, self-renewal, and apoptotic protection of these lineage-restricted progenitors during non-CSF-mediated induction of differentiation. This approach provides a source of many normal, proliferating myelomonocytic precursor cells, and introduces possible clinical applications of ex vivo expanded myeloid stem cells. PMID- 9973315 TI - Ligand-induced internalization of CD38 results in intracellular Ca2+ mobilization: role of NAD+ transport across cell membranes. AB - CD38, a transmembrane glycoprotein widely expressed in vertebrate cells, is a bifunctional ectoenzyme catalyzing the synthesis and hydrolysis of cyclic ADP ribose (cADPR). cADPR is a universal second messenger that releases calcium from intracellular stores. Since cADPR is generated by CD38 at the outer surface of many cells, where it acts intracellularly, increasing attention is paid to addressing this topological paradox. Recently, we demonstrated that CD38 is a catalytically active, unidirectional transmembrane transporter of cADPR, which then reaches its receptor-operated intracellular calcium stores. Moreover, CD38 was reported to undergo a selective and extensive internalization through non clathrin-coated endocytotic vesicles upon incubating CD38(+) cells with either NAD+ or thiol compounds: these endocytotic vesicles can convert cytosolic NAD into cADPR despite an asymmetric unfavorable orientation that makes the active site of CD38 intravesicular. Here we demonstrate that the cADPR-generating activity of the endocytotic vesicles results in remarkable and sustained increases of intracellular free calcium concentration in different cells exposed to either NAD+, or GSH, or N-acetylcysteine. This effect of CD38-internalizing ligands on intracellular calcium levels was found to involve a two-step mechanism: 1) influx of cytosolic NAD+ into the endocytotic vesicles, mediated by a hitherto unrecognized dinucleotide transport system that is saturable, bidirectional, inhibitable by 8-N3-NAD+, and characterized by poor dinucleotide specificity, low affinity, and high efficiency; 2) intravesicular CD38-catalyzed conversion of NAD+ to cADPR, followed by outpumping of the cyclic nucleotide into the cytosol and subsequent release of calcium from thapsigargin-sensitive stores. This unknown intracellular trafficking of NAD+ and cADPR based on two distinctive and specific transmembrane carriers for either nucleotide can affect the intracellular calcium homeostasis in CD38(+) cells. PMID- 9973316 TI - Oxygen tension modulates beta-globin switching in embryoid bodies. AB - Little is known about the factors influencing the hemoglobin switch in vertebrates during development. Inasmuch as the mammalian conceptus is exposed to changing oxygen tensions in utero, we examined the effect of different oxygen concentrations on beta-globin switching. We used an in vitro model of mouse embryogenesis based on the differentiation of blastocyst-derived embryonic stem cells to embryoid bodies (EBs). Cultivation of EBs at increasing oxygen concentrations (starting at 1% O2) did not influence the temporal expression pattern of embryonic (betaH1) globin compared to the normoxic controls (20% O2). In contrast, when compared to normoxically grown EBs, expression of fetal/adult (betamaj) globin in EBs cultured at varying oxygen concentrations was delayed by about 2 days and persisted throughout differentiation. Quantitation of hemoglobin in EBs using a 2,7-diaminofluorene-based colorimetric assay revealed the appearence of hemoglobin in two waves, an early and a late one. This observation was verified by spectrophotometric analysis of hemoglobin within single EBs. These two waves might reflect the switch of erythropoiesis from yolk sac to fetal liver. Reduced oxygenation is known to activate the hypoxia-inducible factor-1 (HIF-1), which in turn specifically induces expression of a variety of genes among them erythropoietin (EPO). Although EBs increased EPO expression upon hypoxic exposure, the altered beta-globin appearance was not related to EPO levels as determined in EBs overexpressing EPO. Since mRNA from both mouse HIF 1alpha isoforms was detected in all EBs tested at different differentiation stages, we propose that HIF-1 modulates beta-globin expression during development. PMID- 9973317 TI - Myelinolytic lesions in spinal cord of cobalamin-deficient rats are TNF-alpha mediated. AB - Repeated intracerebroventricular (i.c.v.)microinjection of tumor necrosis factor alpha (TNF-alpha) into normal rats causes intramyelin and interstitial edema in the white matter of the spinal cord (SC). This response is identical to that observed in the SC white matter of rats made cobalamin (Cbl) deficient by total gastrectomy (TG). Immunoblot analysis showed that: 1) the level of the biologically active form of the TNF-alpha protein (17 kDa) is higher in the SC of totally gastrectomized (TGX) rats 2 months after TG, i.e., at the postoperative time when edema is observed; 2) SC levels of TNF-alpha protein (17 kDa) in 2-mo TGX-, Cbl-treated rats are reduced to control. Repeated i.c.v. microinjections of anti-TNF-alpha antibodies, transforming growth factor-beta1 (TGF-beta1) or interleukin-6 (IL-6) into TGX rats, begun shortly after TG, substantially reduced both intramyelin and interstitial edema in the SC white matter. This study provides the first evidence that the hallmark myelin damage of Cbl-deficient central neuropathy, which is a pure myelinolytic disease, is not caused directly by the withdrawal of the vitamin itself, but reflects enhanced production of the biologically active form of TNF-alpha by SC cells. This study thus supports the view that TGF-beta1 and IL-6 may act as neuroprotective agents in Cbl deficiency central neuropathy. PMID- 9973318 TI - A role for preadipocytes as macrophage-like cells. AB - Several lines of evidence have supported a link betweeen adipose tissue and immunocompetent cells. This link is illustrated in obesity, where excess adiposity and impaired immune function have been described in both humans and genetically obese rodents. In addition, numerous factors involved in inflammatory response are secreted by both preadipocytes and macrophages. Here we show that proliferating preadipocytes in cell lines and primary cultures, develop phagocytic activity toward microorganisms. This is demonstrated by phagocytosis assays and confocal microscopy. This function disappears when preadipocytes stop proliferating and differentiate into adipocytes. After phagocytosis, preadipocytes show microbicide activity via an oxygen-dependent mechanism. In addition, preadipocytes as well as adipocytes are stained with MOMA-2, a marker of monocyte-macrophage lineage, but are negative for specific mature macrophage markers (F4/80 and Mac-1). These results suggest that preadipocytes could function as macrophage-like cells and raise the possibility of a potential direct involvement of adipose tissue in inflammatory processes. PMID- 9973319 TI - Regulation of the L-type Ca2+ channel during cardiomyogenesis: switch from NO to adenylyl cyclase-mediated inhibition. AB - In adult mammalian cardiomyocytes, stimulation of muscarinic receptors counterbalances the beta-adrenoceptor-mediated increase in myocardial contractility and heart rate by decreasing the L-type Ca2+ current (ICa) (1, 2). This effect is mediated via inhibition of adenylyl cyclase and subsequent reduction of cAMP-dependent phosphorylation of voltage-dependent L-type Ca2+ channels (3). Little is known, however, about the nature and origin of this pivotal inhibitory pathway. Using embryonic stem cells as an in vitro model of cardiomyogenesis, we found that muscarinic agonists depress ICa by 58 +/-3% (n=34) in early stage cardiomyocytes lacking functional beta-adrenoceptors. The cholinergic inhibition is mediated by the nitric oxide (NO)/cGMP system since it was abolished by application of NOS inhibitors (L-NMA, L-NAME), an inhibitor of the soluble guanylyl cyclase (ODQ), and a selective phosphodiesterase type II antagonist (EHNA). The NO/cGMP-mediated ICa depression was dependent on a reduction of cAMP/protein kinase A (PKA) levels since application of the catalytic subunit of PKA or of the PKA inhibitor PK) prevented the carbachol effect. In late development stage cells, as reported for ventricular cardiomyocytes (2, 4), muscarinic agonists had no effect on basal ICa but antagonized beta-adrenoceptor-stimulated ICa by 43 +/-4% (n=16). This switch in signaling pathways during development is associated with distinct changes in expression of the two NO-producing isoenzymes, eNOS and iNOS, respectively. These findings indicate a fundamental role for NO as a signaling molecule during early embryonic development and demonstrate a switch in the signaling cascades governing ICa regulation. PMID- 9973320 TI - Sustained microgravity reduces intrinsic wound healing and growth factor responses in the rat. AB - Spaceflight is known to diminish bone mass and reduce immune function, suggesting that repair of connective tissue might be impaired in a microgravity environment. Fisher 344 rats were used to test wound healing responses in the orbiting Space Shuttle Endeavour by preflight implantation of polyvinyl acetal sponge disks in which pellets were placed to release either platelet-derived growth factor (PDGF BB), basic fibroblast growth factor (bFGF), or placebo. Control groups on the ground included a matched environment group in similar housing modules and temperature control groups in cages at 22 degreesC and 28 degreesC. After 12 days of implantation and 10 days in orbit, the removed sponges were analyzed for histological and biochemical responses. Growth factor responses were histologically evident after release of PDGF-BB and bFGF in ground controls, whereas only immediate-release bFGF and delayed-release PDGF-BB showed significant responses in microgravity. Biochemical data confirmed that cellularity was increased by both factors in ground sponges; however, this response was significantly blunted in flight sponges (P<0.005, ANOVA), irrespective timing of factor release. Collagen content was 62% lower in sponges from animals with 10 days of microgravity exposure (P<0.01, ANOVA) and further reduced by bFGF. These data suggest that orbital exposure retards the capacity of wounds to heal and respond to exogenous stimuli. PMID- 9973321 TI - Invasive isolates of Neisseria meningitidis possess enhanced immunoglobulin A1 protease activity compared to colonizing strains. AB - Neisseria meningitidis, Haemophilus influenzae, and Streptococcus pneumoniae possess the ability to cleave human IgA1 antibodies, and all successfully colonize and occasionally invade the human upper respiratory tract. N. meningitidis invades the bloodstream after a period of nasopharyngeal colonization. We directly compared levels of IgA1 protease activity in strains (n=52) derived from the cerebrospinal fluid or blood of patients with meningococcal disease with strains of N. meningitidis obtained from asymptomatic carriers (n=25). IgA1 protease activity was determined by a sensitive semiquantitative ELISA assay. Levels of IgA1 protease activity were significantly higher (P<0.0001) in strains associated with invasive meningococcal disease (98% with detectable activity, mean = 580 mU) than with those obtained from asymptomatic carriers (76% with detectable activity, mean = 280 mU). Despite marked variation in enzyme activity, almost all strains (96%) possessed the gene for IgA1 protease. Given the panmictic population structure of the bacterial isolates investigated, these data, obtained from two groups infected with N. meningitidis, but with markedly different clinical outcomes, provide the first quantitative evidence that IgA1 protease activity is a virulence determinant that contributes to the pathogenic phenotype, and suggest IgA1 protease as a potential target for prophylaxis. PMID- 9973322 TI - Caspase-mediated cleavage of APC results in an amino-terminal fragment with an intact armadillo repeat domain. AB - During the effector phase of apoptosis, caspase activation appears to be responsible for the distinctive structural changes of apoptosis and perhaps for some of the changes in function of the doomed cells. There is therefore interest in identifying caspase substrates and the details of the cleavage events. Here we define precisely the event responsible for generation of a stable 90 kDa fragment from the oncosuppressor protein adenomatous polyposis coli (APC). Using synthetic radiolabeled APC peptides as substrate, we demonstrate cleavage by cytosolic extracts from preapoptotic cells. This cleavage was reproduced by recombinant caspase-3 and blocked by a tetrapeptide inhibitor Ac-DEVD-CHO, which is specific for caspase-3 family members. Inhibitors specific for caspase-1 and -8 however, were less effective in blocking APC cleavage. Mutation of a candidate DNID caspase-3 target site completely abolished cleavage. This cleavage may be of biological importance since the 90 kDa fragment consists of a sequence that is highly conserved in the human, rat, mouse, Xenopus, and Drosophila APC, although wide sequence divergence is observed in Drosophila immediately carboxy-terminal to the DNID site. Furthermore, cleavage at this site separates two significant functional domains: an amino-terminal armadillo repeat and an adjacent series of beta-catenin binding sites. Further circumstantial evidence for the significance of APC-related pathways in apoptosis is provided by the observation that apoptosis also induces cleavage of beta-catenin itself, a protein known to accumulate in cells depleted in functional APC and that appears to link cell-cell signaling to changes in transcription and cell movement. PMID- 9973323 TI - Enhancement by vasoactive intestinal peptide of gamma-interferon production by antigen-stimulated type 1 helper T cells. AB - Vasoactive intestinal peptide (VIP) is a neuroendocrine mediator in immune tissues that affects many T cell functions through two homologous high-affinity G protein-coupled receptors, termed VIPR1 and VIPR2. Antigen-stimulated secretion of gamma-interferon (IFN-gamma) by sperm whale myoglobin-specific Th1 cells of DBA/2 mouse I-Ed-restricted clones, which express VIPR1 and VIPR2, was enhanced by 10(-10) M to 10(-7) M VIP. Enhancement of IFN-gamma secretion reached a mean maximum of fourfold for VIP and threefold for a VIPR2-selective agonist, without any effect of a VIPR1-selective agonist. Secretion of IFN-gamma by PMA and ionomycin-stimulated clones of Th1 cells was not altered by VIP. Antigen stimulated secretion of IFN-gamma by T cell receptor-transgenic, influenza hemagglutinin-specific, and cytokine-differentiated mouse lymph node Th1 cells, which also express VIPR1 and VIPR2, was enhanced by 10(-10) M to 10(-8) M VIP. Enhancement of IFN-gamma secretion increased to a maximum of 14-fold for VIP, 14 fold for the VIPR2-selective agonist, and 20-fold for the VIPR1-selective agonist. In contrast to VIP suppression of interleukin production and lack of effect on IFN-gamma production by T cells stimulated with anti-CD3 antibody or a mitogenic lectin, generation of IFN-gamma by antigen-stimulated T cells is enhanced significantly by physiological concentrations of VIP. PMID- 9973324 TI - Identification of 'tissue' transglutaminase binding proteins in neural cells committed to apoptosis. AB - Overexpression of 'tissue' transglutaminase (tTG) in the human neuroblastoma cells increases spontaneous apoptosis and renders these cells highly susceptible to death induced by various stimuli. We used immunoprecipitation to identify cellular proteins that interact specifically with tTG in SK-N-BE(2) -derived stable transfectants. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis showed that tTG binding proteins have molecular masses of 110, 50, 22, 14, and 12 kDa. Microsequencing and computer search analyses allowed us to identify these polypeptides as the beta-tubulin (50 kDa), the histone H2B (14 kDa), and two GST P1-1-truncated forms (22 and 12 kDa). The specificity of the interaction between tTG and these proteins was confirmed by competing tTG binding with purified enzyme and by detecting tTG in immunoprecipitates obtained using beta-tubulin or GST P1-1 mAb's. Here we demonstrate that the GST P1-1 acts as an efficient acyl donor as well as acceptor tTG substrate both in cells and in vitro. The tTG-catalyzed polymerization of GST P1-1 leads to its functional inactivation and is competitively inhibited by GSH. By contrast, the tTG-beta tubulin interaction does not result in the cross-linking of this cytoskeletal protein, which suggests that microtubules act as the anchorage site for tTG and GST P1-1 interaction. PMID- 9973325 TI - Elementary [Ca2+]i signals generated by electroporation functionally mimic those evoked by hormonal stimulation. AB - The generation of oscillations and global Ca2+ waves relies on the spatio temporal recruitment of elementary Ca2+ signals, such as 'Ca2+ puffs'. Each elementary signal contributes a small amount of Ca2+ into the cytoplasm, progressively promoting neighboring Ca2+ release sites into an excitable state. Previous studies have indicated that increases in frequency or amplitude of such hormone-evoked elementary Ca2+ signals are necessary to initiate Ca2+ wave propagation. In the present study, an electroporation device was used to rapidly and reversibly permeabilize the plasma membrane of HeLa cells and to allow a limited influx of Ca2+. With low field intensities (100-500 V/cm), brief (50-100 micros) electroporation triggered localized Ca2+ signals that resembled hormone evoked Ca2+ puffs, but not global signals. With such low intensity electroporative pulses, the Ca2+ influx component was usually undetectable, confirming that the electroporation-induced local signals represented Ca2+ puffs arising from the opening of intracellular Ca2+ release channels. Increasing either the frequency at which low-intensity electroporative pulses were applied, or the intensity of a single electroporative pulse (>500 V/cm), resulted in caffeine-sensitive regenerative Ca2+ waves. We suggest that Ca2+ puffs caused by electroporation functionally mimic hormone-evoked elementary events and can activate global Ca2+ signals if they provide a sufficient trigger. PMID- 9973327 TI - Differential regulation of somatostatin receptor types 1-5 in rat aorta after angioplasty. AB - Treatment of restenosis after angioplasty with octapeptide somatostatin (SST) analogs has met with variable success. These analogs bind with high affinity to only two SST receptor (SSTR) subtypes (2 and 5), display moderate affinity for SSTR3, and low affinity for SSTR1 and 4. To optimize the vasculoprotective effect of SST, we have investigated the pattern of expression of all five SSTRs in rat thoracic aorta in the resting state and at 15 min, 3, 7, and 14 days after balloon endothelial denudation. SSTR1-5 were analyzed as mRNA by semiquantitative reverse transcriptase-polymerase chain reaction and as protein by immunocytochemistry. All five SSTRs were expressed in rat aorta both as mRNA and protein and displayed a time-dependent, subtype-selective response to endothelial denudation. mRNA for SSTR1 and 2 increased acutely (SSTR1 > SSTR2) on days 3 and 7, coincident with smooth muscle cell (SMC) proliferation, and declined to basal levels by day 14. SSTR3 and 4 displayed a different pattern with a delayed, more gradual increase in mRNA beginning at days 3-7 and continued to increase thereafter. SSTR5 mRNA was constitutively expressed at a low level and showed no change during the 2 wk postinjury period. By immunohistochemistry, SSTR1-5 antigens were localized predominantly in SMC that were present in the media or had migrated into the intima; antigen expression correlated with receptor mRNA expression. Notably, only SSTR1,3,4 were expressed in the intima: SSTR1 and 4 during the proliferative burst and SSTR3 and 4 after proliferation, when SMC migration into the intima continues. These results demonstrate dynamic changes in SSTR1-5 expression after vascular trauma localized to areas of vascular SMC migration and replication. In view of their early and prominent induction, SSTR1 may be the optimal subtype to target for inhibition of myointimal proliferation, and SSTR3 and 4 for migration and remodeling. PMID- 9973326 TI - Role of ets factors in the activity and endothelial cell specificity of the mouse Tie gene promoter. AB - The Tie gene encodes an endothelial cell receptor tyrosine kinase necessary for normal vascular development. The Tie gene promoter targets expression of heterologous genes specifically to endothelial cells in transgenic mice. Here we have characterized the promoter sequences critical for endothelial cell-specific activity in cultured cells and transgenic mice. Progressive deletions and site directed mutations of the promoter showed that the critical endothelial cell specific elements are an octamer transcription factor binding site and several Ets binding sites located in two clusters within 300 bp upstream of the major transcription initiation site. Among members of the Ets transcription factor family tested, NERF-2 (a novel transcription factor related to the ets factor ELF 1), which is expressed in endothelial cells, and ETS2 showed the strongest transactivation of the Tie promoter; ETS1 gave lower levels of stimulation and the other Ets factors gave little or no transactivation. Furthermore, the Tie promoter directed the production of high amounts of human growth hormone into the circulation of transgenic mice. The secreted amounts correlated with transgene copy number, being relatively insensitive to the effects of the transgene integration site. These properties suggest that Tie promoter activity is controlled by endothelial cell Ets factors and that it has potential for use in vectors for endothelial cell-specific gene expression. PMID- 9973328 TI - A new role for neurotrophins: involvement of brain-derived neurotrophic factor and neurotrophin-4 in hair cycle control. AB - Neurotrophins exert many biological effects not directly targeted at neurons, including modulation of keratinocyte proliferation and apoptosis in vitro. Here we exploit the cyclic growth and regression activity of the murine hair follicle to explore potential nonneuronal functions of neurotrophins in the skin, and analyze the follicular expression and hair growth-modulatory function of BDNF, NT 4, and their high-affinity receptor, TrkB. The cutaneous expression of BDNF and NT-4 mRNA was strikingly hair cycle dependent and peaked during the spontaneous, apoptosis-driven hair follicle regression (catagen). During catagen, BDNF mRNA and immunoreactivity, as well as NT-4-immunoreactivity, were expressed in the regressing hair follicle compartments, whereas TrkB mRNA and immunoreactivity were seen in dermal papilla fibroblasts, epithelial strand, and hair germ. BDNF or NT-4 knockout mice showed significant catagen retardation, whereas BDNF overexpressing mice displayed acceleration of catagen and significant shortening of hair length. Finally, BDNF and NT-4 accelerated catagen development in murine skin organ culture. Together, our data suggest that BDNF and NT-4 play a previously unrecognized role in skin physiology as agents of hair growth control. Thus, TrkB agonists and antagonists deserve exploration as novel hair growth modulatory drugs for the management of common hair growth disorders. PMID- 9973329 TI - (R)-alpha-lipoic acid-supplemented old rats have improved mitochondrial function, decreased oxidative damage, and increased metabolic rate. AB - A diet supplemented with (R)-lipoic acid, a mitochondrial coenzyme, was fed to old rats to determine its efficacy in reversing the decline in metabolism seen with age. Young (3 to 5 months) and old (24 to 26 months) rats were fed an AIN 93M diet with or without (R)-lipoic acid (0.5% w/w) for 2 wk, killed, and their liver parenchymal cells were isolated. Hepatocytes from untreated old rats vs. young controls had significantly lower oxygen consumption (P<0. 03) and mitochondrial membrane potential. (R)-Lipoic acid supplementation reversed the age-related decline in O2 consumption and increased (P<0.03) mitochondrial membrane potential. Ambulatory activity, a measure of general metabolic activity, was almost threefold lower in untreated old rats vs. controls, but this decline was reversed (P<0.005) in old rats fed (R)-lipoic acid. The increase of oxidants with age, as measured by the fluorescence produced on oxidizing 2',7' dichlorofluorescin, was significantly lowered in (R)-lipoic acid supplemented old rats (P<0.01). Malondialdehyde (MDA) levels, an indicator of lipid peroxidation, were increased fivefold with age in cells from unsupplemented rats. Feeding rats the (R)-lipoic acid diet reduced MDA levels markedly (P<0.01). Both glutathione and ascorbic acid levels declined in hepatocytes with age, but their loss was completely reversed with (R)-lipoic acid supplementation. Thus, (R)-lipoic acid supplementation improves indices of metabolic activity as well as lowers oxidative stress and damage evident in aging. PMID- 9973331 TI - Physiological characterization of Pseudomonas aeruginosa during exotoxin A synthesis: glutamate, iron limitation, and aconitase activity. AB - Glutamate enhances the yield of exotoxin A (ETA), which is induced by iron limitation, from Pseudomonas aeruginosa. We tested the possibility that glutamate affects growth during iron restriction. We confirmed that iron limitation caused early entry into stationary phase but had no effect on the exponential growth rate. We showed that glutamate, as well as citrate and isocitrate, partially overcame this growth limitation. Glutamate had no effect on toxA (ETA-encoding) transcription, which implies that glutamate primarily increases the number of toxin-producing cells. In contrast, citrate and isocitrate diminished toxA transcription. Since glutamate, citrate, and isocitrate stimulated growth, we suspected a block in the citric acid cycle. Iron limitation reduced the activity of the iron-containing aconitase 12-fold but had no effect on isocitrate dehydrogenase activity, which was assayed as a control. There is a reciprocal relationship between aconitase activity and ETA synthesis, and this correlation does not appear to be coincidental because aconitase-specific effectors affect ETA synthesis. We tested whether a metabolic block is sufficient to induce ETA synthesis, but an aconitase-specific inhibitor diminished ETA production, which argues against this possibility. Finally, we present preliminary evidence that iron limitation may reversibly and posttranslationally inactivate aconitase in vivo. In summary, the environmental factors that stimulate ETA synthesis are related: glutamate bypasses an iron limitation-dependent metabolic block that causes entry into stationary phase. We speculate that one or more of the aconitases in P. aeruginosa may contribute to the control of virulence factor synthesis. PMID- 9973330 TI - Bacterial adhesins: common themes and variations in architecture and assembly. PMID- 9973332 TI - Mycoplasma pneumoniae protein P30 is required for cytadherence and associated with proper cell development. AB - The attachment organelle of Mycoplasma pneumoniae is a polar, tapered cell extension containing an intracytoplasmic, electron-dense core. This terminal structure is the leading end in gliding motility, and its duplication is thought to precede cell division, raising the possibility that mutations affecting cytadherence also confer a defect in motility or cell development. Mycoplasma surface protein P30 is associated with the attachment organelle, and P30 mutants II-3 and II-7 do not cytadhere. In this study, the recombinant wild-type but not the mutant II-3 p30 allele restored cytadherence when transformed into P30 mutants by recombinant transposon delivery. The mutations associated with loss of P30 in mutant II-3 and reacquisition of P30 in cytadhering revertants thereof were identified by nucleotide sequencing of the p30 gene. Morphological abnormalities that included ovoid or multilobed cells having a poorly defined tip structure were associated with loss of P30. Digital image analysis confirmed quantitatively the morphological differences noted visually. Transformation of the P30 mutants with the wild-type p30 allele restored a normal morphology, as determined both visually and by digital image analysis, suggesting that P30 plays a role in mycoplasma cell development. Finally, the P30 mutants localized the adhesin protein P1 to the terminal organelle, indicating that P30 is not involved in P1 trafficking but may be required for its receptor-binding function. PMID- 9973333 TI - Presence of acetyl coenzyme A (CoA) carboxylase and propionyl-CoA carboxylase in autotrophic Crenarchaeota and indication for operation of a 3-hydroxypropionate cycle in autotrophic carbon fixation. AB - The pathway of autotrophic CO2 fixation was studied in the phototrophic bacterium Chloroflexus aurantiacus and in the aerobic thermoacidophilic archaeon Metallosphaera sedula. In both organisms, none of the key enzymes of the reductive pentose phosphate cycle, the reductive citric acid cycle, and the reductive acetyl coenzyme A (acetyl-CoA) pathway were detectable. However, cells contained the biotin-dependent acetyl-CoA carboxylase and propionyl-CoA carboxylase as well as phosphoenolpyruvate carboxylase. The specific enzyme activities of the carboxylases were high enough to explain the autotrophic growth rate via the 3-hydroxypropionate cycle. Extracts catalyzed the CO2-, MgATP-, and NADPH-dependent conversion of acetyl-CoA to 3-hydroxypropionate via malonyl-CoA and the conversion of this intermediate to succinate via propionyl-CoA. The labelled intermediates were detected in vitro with either 14CO2 or [14C]acetyl CoA as precursor. These reactions are part of the 3-hydroxypropionate cycle, the autotrophic pathway proposed for C. aurantiacus. The investigation was extended to the autotrophic archaea Sulfolobus metallicus and Acidianus infernus, which showed acetyl-CoA and propionyl-CoA carboxylase activities in extracts of autotrophically grown cells. Acetyl-CoA carboxylase activity is unexpected in archaea since they do not contain fatty acids in their membranes. These aerobic archaea, as well as C. aurantiacus, were screened for biotin-containing proteins by the avidin-peroxidase test. They contained large amounts of a small biotin carrying protein, which is most likely part of the acetyl-CoA and propionyl-CoA carboxylases. Other archaea reported to use one of the other known autotrophic pathways lacked such small biotin-containing proteins. These findings suggest that the aerobic autotrophic archaea M. sedula, S. metallicus, and A. infernus use a yet-to-be-defined 3-hydroxypropionate cycle for their autotrophic growth. Acetyl-CoA carboxylase and propionyl-CoA carboxylase are proposed to be the main CO2 fixation enzymes, and phosphoenolpyruvate carboxylase may have an anaplerotic function. The results also provide further support for the occurrence of the 3 hydroxypropionate cycle in C. aurantiacus. PMID- 9973334 TI - Pseudomonas aeruginosa fur overlaps with a gene encoding a novel outer membrane lipoprotein, OmlA. AB - A novel outer membrane lipoprotein in Pseudomonas aeruginosa is encoded by the omlA gene, which was identified immediately upstream of the fur (ferric uptake regulator) gene. The omlA and fur genes were divergently transcribed and had overlapping promoter regions. The proximal fur P2 promoter and the omlA promoter shared a 5-bp DNA motif for their -10 promoter elements. The distal fur P1 promoter was located within the omlA coding sequence, and the omlA and fur T1 mRNAs overlapped by 154 nucleotides. Optimal expression of both fur and omlA required roughly 200 bp of DNA upstream of the promoter regions, suggesting the presence of cis-acting transcriptional activation elements located within the omlA and fur genes, respectively. The levels of Fur and OmlA proteins had no influence on omlA or fur expression, excluding any trans-acting cross-regulation between fur and omlA. Expression of omlA was constitutive regardless of growth phase, oxygen tension, iron concentration, pH, and temperature. OmlA contained a signal sequence typical of bacterial lipoproteins, with a cysteine as a putative cleavage and lipid attachment site. Inhibition of signal peptidase II by globomycin resulted in failure to process OmlA, thus giving strong evidence that OmlA is a lipoprotein. Cell fractionation followed by Western blot analysis indicated that all OmlA protein is localized in the outer membrane. Mature OmlA was an acidic (pI = 4. 5) protein of 17.3 kDa and had close to 40% amino acid sequence identity to SmpA (small protein A) of Escherichia coli, Vibrio cholerae, and Haemophilus influenzae, a protein of unknown function. All P. aeruginosa strains tested as well as Pseudomonas fluorescens were found to produce OmlA. A mutant strain with impaired production of OmlA but no change in the expression of the overlapping fur gene was constructed. The omlA mutant was hypersusceptible to anionic detergents such as sodium dodecyl sulfate and deoxycholate, and it showed increased susceptibility to various antibiotics, including nalidixic acid, rifampin, novobiocin, and chloramphenicol. A structural role of OmlA in maintaining the cell envelope integrity is proposed. PMID- 9973335 TI - Genetic and transcriptional analyses of the Vibrio cholerae mannose-sensitive hemagglutinin type 4 pilus gene locus. AB - The mannose-sensitive hemagglutinin (MSHA) of the Vibrio cholerae O1 El Tor biotype is a member of the family of type 4 pili. Type 4 pili are found on the surface of a variety of gram-negative bacteria and have demonstrated importance as host colonization factors, bacteriophage receptors, and mediators of DNA transfer. The gene locus required for the assembly and secretion of the MSHA pilus has been localized to a 16.7-kb region of the V. cholerae chromosome. Sixteen genes required for hemagglutination, including five that encode prepilin or prepilin-like proteins, have been identified. Examination of MSHA-specific cDNAs has localized two promoters that drive expression of these genes. This evidence indicates that the MSHA gene locus is transcriptionally organized into two operons, one encoding the secretory components and the other encoding the structural subunits, an arrangement unique among previously characterized type 4 pilus loci. The genes flanking the MSHA locus encode proteins that show homology to YhdA and MreB of Escherichia coli. In E. coli, the yhdA and mreB genes are adjacent to each other on the chromosome. The finding that the MSHA locus lies between these two E. coli homologs and that it is flanked by a 7-bp direct repeat suggests that the MSHA locus may have been acquired as a mobile genetic element. PMID- 9973336 TI - Cell cycle control of a holdfast attachment gene in Caulobacter crescentus. AB - Attachment to surfaces by the prosthecate bacterium Caulobacter crescentus is mediated by an adhesive organelle, the holdfast, found at the tip of the stalk. Indirect evidence suggested that the holdfast first appears at the swarmer pole of the predivisional cell. We used fluorescently labeled lectin and transmission electron microscopy to detect the holdfast in different cell types. While the holdfast was readily detectable in stalked cells and at the stalked poles of predivisional cells, we were unable to detect the holdfast in swarmer cells or at the flagellated poles of predivisional cells. This suggests that exposure of the holdfast to the outside of the cell occurs during the differentiation of swarmer to stalked cells. To investigate the timing of holdfast synthesis and exposure to the outside of the cell, we have examined the regulation of a holdfast attachment gene, hfaA. The hfaA gene is part of a cluster of four genes (hfaABDC), identified in strain CB2A and involved in attachment of the holdfast to the polar region of the cell. We have identified the hfaA gene in the synchronizable C. crescentus strain CB15. The sequence of the CB2A hfaA promoter suggested that it was regulated by sigma54. We show that the transcription of hfaA from either strain is not dependent on sigma54. Using a hfaA-lacZ fusion, we show that the transcription of hfaA is temporally regulated during the cell cycle, with maximal expression in late-predivisional cells. This increase in expression is largely due to the preferential transcription of hfaA in the swarmer pole of the predivisional cell. PMID- 9973337 TI - Identification of a Streptococcus pneumoniae gene locus encoding proteins of an ABC phosphate transporter and a two-component regulatory system. AB - The Escherichia coli Pst system belongs to the family of ABC transporters. It is part of a phosphate (PHO) regulon which is regulated by extracellular phosphate. Under conditions of phosphate limitation, the response regulator PhoB is phosphorylated by the histidine kinase PhoR and binds to promoters that share a consensus PHO box. Under conditions of phosphate excess, PhoR, Pst, and PhoU downregulate the PHO regulon. Screening of a library of pneumococcal mutants with defects in exported proteins revealed a putative two-component regulatory system, PnpR-PnpS, and a downstream ABC transporter, similar to the Pst system in E. coli including a gene encoding a PhoU protein. Similar to E. coli, mutagenesis of the ATP-binding cassette gene, pstB, resulted in decreased uptake of phosphate. The effects of the loss of the pneumococcal Pst system extended to decreased transformation and lysis. Withdrawal of phosphate led to transformation deficiency in the parent strain R6x but not to penicillin tolerance, suggesting that reduced bacterial death was independent of phosphate. None of these phenotypes was observed in the pneumococcal loss-of-function mutant phoU. By using a lacZ reporter construct, it was demonstrated that expression of the two component regulatory system PnpR-PnpS was not influenced by different concentrations of phosphate. These results suggest a more complex role of the Pst system in pneumococcal physiology than in that of E. coli. PMID- 9973338 TI - Analysis of phosphorylated sphingolipid long-chain bases reveals potential roles in heat stress and growth control in Saccharomyces. AB - Sphingolipid long-chain bases and their phosphorylated derivatives, for example, sphingosine-1-phosphate in mammals, have been implicated as signaling molecules. The possibility that Saccharomyces cerevisiae cells also use long-chain-base phosphates to regulate cellular processes has only recently begun to be examined. Here we present a simple and sensitive procedure for analyzing and quantifying long-chain-base phosphates in S. cerevisiae cells. Our data show for the first time that phytosphingosine-1-phosphate (PHS-1-P) is present at a low but detectable level in cells grown on a fermentable carbon source at 25 degreesC, while dihydrosphingosine-1-phosphate (DHS-1-P) is only barely detectable. Shifting cells to 37 degreesC causes transient eight- and fivefold increases in levels of PHS-1-P and DHS-1-P, respectively, which peak after about 10 min. The amounts of both compounds return to the unstressed levels by 20 min after the temperature shift. These data are consistent with PHS-1-P and DHS-1-P being signaling molecules. Cells unable to break down long-chain-base phosphates, due to deletion of DPL1 and LCB3, show a 500-fold increase in PHS-1-P and DHS-1-P levels, grow slowly, and survive a 44 degreesC heat stress 10-fold better than parental cells. These and other data for dpl1 or lcb3 single-mutant strains suggest that DHS-1-P and/or PHS-1-P act as signals for resistance to heat stress. Our procedure should expedite experiments to determine how the synthesis and breakdown of these compounds is regulated and how the compounds mediate resistance to elevated temperature. PMID- 9973340 TI - Spectra of spontaneous growth-dependent and adaptive mutations at ebgR. AB - A comparison of the spectra of spontaneous growth-dependent and adaptive mutations in ebgR shows that both spectra are dominated by insertion sequence (IS)-mediated mutations. The difference between growth-dependent mutations (61% IS mediated) and adaptive mutations (80% IS mediated) is highly significant (P < 0.0001). In contrast, the spectra of growth-dependent and adaptive non-IS mediated mutations do not differ from each other and therefore do not provide support for the hypothesis that adaptive and growth-dependent mutations arise by substantially different mechanisms. PMID- 9973339 TI - Expression and study of recombinant ExoM, a beta1-4 glucosyltransferase involved in succinoglycan biosynthesis in Sinorhizobium meliloti. AB - Here we report on the overexpression and in vitro characterization of a recombinant form of ExoM, a putative beta1-4 glucosyltransferase involved in the assembly of the octasaccharide repeating subunit of succinoglycan from Sinorhizobium meliloti. The open reading frame exoM was isolated by PCR and subcloned into the expression vector pET29b, allowing inducible expression under the control of the T7 promoter. Escherichia coli BL21(DE3)/pLysS containing exoM expressed a novel 38-kDa protein corresponding to ExoM in N-terminal fusion with the S-tag peptide. Cell fractionation studies showed that the protein is expressed in E. coli as a membrane-bound protein in agreement with the presence of a predicted C-terminal transmembrane region. E. coli membrane preparations containing ExoM were shown to be capable of transferring glucose from UDP-glucose to glycolipid extracts from an S. meliloti mutant strain which accumulates the ExoM substrate (Glcbeta1-4Glcbeta1-3Gal-pyrophosphate-polyprenol). Thin-layer chromatography of the glycosidic portion of the ExoM product showed that the oligosaccharide formed comigrates with an authentic standard. The oligosaccharide produced by the recombinant ExoM, but not the starting substrate, was sensitive to cleavage with a specific cellobiohydrolase, consistent with the formation of a beta1-4 glucosidic linkage. No evidence for the transfer of multiple glucose residues to the glycolipid substrate was observed. It was also found that ExoM does not transfer glucose to an acceptor substrate that has been hydrolyzed from the polyprenol anchor. Furthermore, neither glucose, cellobiose, nor the trisaccharide Glcbeta1-4Glcbeta1-3Glc inhibited the transferase activity, suggesting that some feature of the lipid anchor is necessary for activity. PMID- 9973341 TI - The signal transduction protein GlnK is required for NifL-dependent nitrogen control of nif gene expression in Klebsiella pneumoniae. AB - In Klebsiella pneumoniae, transcription of the nitrogen fixation (nif) genes is regulated in response to molecular oxygen or availability of fixed nitrogen by the coordinated activities of the nifA and nifL gene products. NifA is a nif specific transcriptional activator, the activity of which is inhibited by interaction with NifL. Nitrogen control of NifL occurs at two levels: transcription of the nifLA operon is regulated by the global ntr system, and the inhibitory activity of NifL is controlled in response to fixed nitrogen by an unknown factor. K. pneumoniae synthesizes two PII-like signal transduction proteins, GlnB, which we have previously shown not to be involved in the response of NifL to fixed nitrogen, and the recently identified protein GlnK. We have now cloned the K. pneumoniae glnK gene, studied its expression, and shown that a null mutation in glnK prevents NifL from responding to the absence of fixed nitrogen, i.e., from relieving the inhibition of NifA activity. Hence, GlnK appears to be involved, directly or indirectly, in NifL-dependent regulation of nif gene expression in K. pneumoniae. Comparison of the GlnB and GlnK amino acid sequences from six species of proteobacteria identifies five residues (residues 3, 5, 52, 54, and 64) which serve to distinguish the GlnB and GlnK proteins. PMID- 9973342 TI - An unusual oxygen-sensitive, iron- and zinc-containing alcohol dehydrogenase from the hyperthermophilic archaeon Pyrococcus furiosus. AB - Pyrococcus furiosus is a hyperthermophilic archaeon that grows optimally at 100 degreesC by the fermentation of peptides and carbohydrates to produce acetate, CO2, and H2, together with minor amounts of ethanol. The organism also generates H2S in the presence of elemental sulfur (S0). Cell extracts contained NADP dependent alcohol dehydrogenase activity (0.2 to 0.5 U/mg) with ethanol as the substrate, the specific activity of which was comparable in cells grown with and without S0. The enzyme was purified by multistep column chromatography. It has a subunit molecular weight of 48,000 +/- 1,000, appears to be a homohexamer, and contains iron ( approximately 1.0 g-atom/subunit) and zinc ( approximately 1.0 g atom/subunit) as determined by chemical analysis and plasma emission spectroscopy. Neither other metals nor acid-labile sulfur was detected. Analysis using electron paramagnetic resonance spectroscopy indicated that the iron was present as low-spin Fe(II). The enzyme is oxygen sensitive and has a half-life in air of about 1 h at 23 degreesC. It is stable under anaerobic conditions even at high temperature, with half-lives at 85 and 95 degreesC of 160 and 7 h, respectively. The optimum pH for ethanol oxidation was between 9. 4 and 10.2 (at 80 degreesC), and the apparent Kms (at 80 degreesC) for ethanol, acetaldehyde, NADP, and NAD were 29.4, 0.17, 0.071, and 20 mM, respectively. P. furiosus alcohol dehydrogenase utilizes a range of alcohols and aldehydes, including ethanol, 2-phenylethanol, tryptophol, 1,3-propanediol, acetaldehyde, phenylacetaldehyde, and methyl glyoxal. Kinetic analyses indicated a marked preference for catalyzing aldehyde reduction with NADPH as the electron donor. Accordingly, the proposed physiological role of this unusual alcohol dehydrogenase is in the production of alcohols. This reaction simultaneously disposes of excess reducing equivalents and removes toxic aldehydes, both of which are products of fermentation. PMID- 9973343 TI - Purification and molecular characterization of the tungsten-containing formaldehyde ferredoxin oxidoreductase from the hyperthermophilic archaeon Pyrococcus furiosus: the third of a putative five-member tungstoenzyme family. AB - Pyrococcus furiosus is a hyperthermophilic archaeon which grows optimally near 100 degreesC by fermenting peptides and sugars to produce organic acids, CO2, and H2. Its growth requires tungsten, and two different tungsten-containing enzymes, aldehyde ferredoxin oxidoreductase (AOR) and glyceraldehyde-3-phosphate ferredoxin oxidoreductase (GAPOR), have been previously purified from P. furiosus. These two enzymes are thought to function in the metabolism of peptides and carbohydrates, respectively. A third type of tungsten-containing enzyme, formaldehyde ferredoxin oxidoreductase (FOR), has now been characterized. FOR is a homotetramer with a mass of 280 kDa and contains approximately 1 W atom, 4 Fe atoms, and 1 Ca atom per subunit, together with a pterin cofactor. The low recovery of FOR activity during purification was attributed to loss of sulfide, since the purified enzyme was activated up to fivefold by treatment with sulfide (HS-) under reducing conditions. FOR uses P. furiosus ferredoxin as an electron acceptor (Km = 100 microM) and oxidizes a range of aldehydes. Formaldehyde (Km = 15 mM for the sulfide-activated enzyme) was used in routine assays, but the physiological substrate is thought to be an aliphatic C5 semi- or dialdehyde, e.g., glutaric dialdehyde (Km = 1 mM). Based on its amino-terminal sequence, the gene encoding FOR (for) was identified in the genomic database, together with those encoding AOR and GAPOR. The amino acid sequence of FOR corresponded to a mass of 68.7 kDa and is highly similar to those of the subunits of AOR (61% similarity and 40% identity) and GAPOR (50% similarity and 23% identity). The three genes are not linked on the P. furiosus chromosome. Two additional (and nonlinked) genes (termed wor4 and wor5) that encode putative tungstoenzymes with 57% (WOR4) and 56% (WOR5) sequence similarity to FOR were also identified. Based on sequence motif similarities with FOR, both WOR4 and WOR5 are also proposed to contain a tungstobispterin site and one [4Fe-4S] cluster per subunit. PMID- 9973345 TI - Hydride-Meisenheimer complex formation and protonation as key reactions of 2,4,6 trinitrophenol biodegradation by Rhodococcus erythropolis. AB - Biodegradation of 2,4,6-trinitrophenol (picric acid) by Rhodococcus erythropolis HLPM-1 proceeds via initial hydrogenation of the aromatic ring system. Here we present evidence for the formation of a hydride-Meisenheimer complex (anionic sigma-complex) of picric acid and its protonated form under physiological conditions. These complexes are key intermediates of denitration and productive microbial degradation of picric acid. For comparative spectroscopic identification of the hydride complex, it was necessary to synthesize this complex for the first time. Spectroscopic data revealed the initial addition of a hydride ion at position 3 of picric acid. This hydride complex readily picks up a proton at position 2, thus forming a reactive species for the elimination of nitrite. Cell extracts of R. erythropolis HLPM-1 transform the chemically synthesized hydride complex into 2,4-dinitrophenol. Picric acid is used as the sole carbon, nitrogen, and energy source by R. erythropolis HLPM-1. PMID- 9973344 TI - Gene targeting in Penicillium chrysogenum: disruption of the lys2 gene leads to penicillin overproduction. AB - Two strategies have been used for targeted integration at the lys2 locus of Penicillium chrysogenum. In the first strategy the disruption of lys2 was obtained by a single crossing over between the endogenous lys2 and a fragment of the same gene located in an integrative plasmid. lys2-disrupted mutants were obtained with 1.6% efficiency when the lys2 homologous region was 4.9 kb, but no homologous integration was observed with constructions containing a shorter homologous region. Similarly, lys2-disrupted mutants were obtained by a double crossing over (gene replacement) with an efficiency of 0.14% by using two lys2 homologous regions of 4.3 and 3.0 kb flanking the pyrG marker. No homologous recombination was observed when the selectable marker was flanked by short lys2 homologous DNA fragments. The disruption of lys2 was confirmed by Southern blot analysis of three different lysine auxotrophs obtained by a single crossing over or gene replacement. The lys2-disrupted mutants lacked alpha-aminoadipate reductase activity (encoded by lys2) and showed specific penicillin yields double those of the parental nondisrupted strain, Wis 54-1255. The alpha-aminoadipic acid precursor is channelled to penicillin biosynthesis by blocking the lysine biosynthesis branch at the alpha-aminoadipate reductase level. PMID- 9973346 TI - Two nucleotide transport proteins in Chlamydia trachomatis, one for net nucleoside triphosphate uptake and the other for transport of energy. AB - The genome of Chlamydia trachomatis, one of the most prominent human pathogens, contains two structural genes coding for proteins, herein called Npt1Ct and Npt2Ct (nucleoside phosphate transporters 1 and 2 of C. trachomatis), exhibiting 68 and 61% similarity, respectively, to the ATP/ADP transporter from the intracellular bacterium Rickettsia prowazekii at the deduced amino acid level. Hydropathy analysis and sequence alignments suggested that both proteins have 12 transmembrane domains. The putative transporters were expressed as histidine tagged proteins in Escherichia coli to study their biochemical properties. His10 Npt1Ct catalyzed ATP and ADP transport in an exchange mode. The apparent Km values were 48 (ATP) and 39 (ADP) microM. ATP and ADP transport was specific since AMP, GTP, CTP, UTP, dATP, dCTP, dGTP, and dTTP did not inhibit uptake. In contrast, His10-Npt2Ct transported all four ribonucleoside triphosphates with apparent Km values of 31 microM (GTP), 302 microM (UTP), 528 microM (CTP), and 1,158 microM (ATP). Ribonucleoside di- and monophosphates and deoxyribonucleotides were not substrates. The protonophore m chlorocarbonylcyanide phenylhydrazone abolished uptake of all nucleoside triphosphates by Npt2Ct. This observation indicated that His10-Npt2Ct acts as a nucleosidetriphosphate/H+ symporter energized by the proton motive force across the Escherichia coli cytoplasmic membrane. We conclude that Npt1Ct provides chlamydiae with energy whereas Npt2Ct catalyzes the net uptake of ribonucleoside triphosphates required for anabolic reactions. PMID- 9973347 TI - Active efflux and diffusion are involved in transport of Pseudomonas aeruginosa cell-to-cell signals. AB - Many gram-negative bacteria communicate by N-acyl homoserine lactone signals called autoinducers (AIs). In Pseudomonas aeruginosa, cell-to-cell signaling controls expression of extracellular virulence factors, the type II secretion apparatus, a stationary-phase sigma factor (sigmas), and biofilm differentiation. The fact that a similar signal, N-(3-oxohexanoyl) homoserine lactone, freely diffuses through Vibrio fischeri and Escherichia coli cells has led to the assumption that all AIs are freely diffusible. In this work, transport of the two P. aeruginosa AIs, N-(3-oxododecanoyl) homoserine lactone (3OC12-HSL) (formerly called PAI-1) and N-butyryl homoserine lactone (C4-HSL) (formerly called PAI-2), was studied by using tritium-labeled signals. When [3H]C4-HSL was added to cell suspensions of P. aeruginosa, the cellular concentration reached a steady state in less than 30 s and was nearly equal to the external concentration, as expected for a freely diffusible compound. In contrast, [3H]3OC12-HSL required about 5 min to reach a steady state, and the cellular concentration was 3 times higher than the external level. Addition of inhibitors of the cytoplasmic membrane proton gradient, such as azide, led to a strong increase in cellular accumulation of [3H]3OC12-HSL, suggesting the involvement of active efflux. A defined mutant lacking the mexA-mexB-oprM-encoded active-efflux pump accumulated [3H]3OC12-HSL to levels similar to those in the azide-treated wild-type cells. Efflux experiments confirmed these observations. Our results show that in contrast to the case for C4-HSL, P. aeruginosa cells are not freely permeable to 3OC12-HSL. Instead, the mexA-mexB-oprM-encoded efflux pump is involved in active efflux of 3OC12-HSL. Apparently the length and/or degree of substitution of the N-acyl side chain determines whether an AI is freely diffusible or is subject to active efflux by P. aeruginosa. PMID- 9973348 TI - Conditional stability of the HemA protein (glutamyl-tRNA reductase) regulates heme biosynthesis in Salmonella typhimurium. AB - In many bacteria, including the enteric species Salmonella typhimurium and Escherichia coli, heme is synthesized starting from glutamate by a pathway in which the first committed step is catalyzed by the hemA gene product, glutamyl tRNA reductase (HemA). We have demonstrated previously that when heme limitation is imposed on cultures of S. typhimurium, HemA enzyme activity is increased 10- to 25-fold. Western (immunoblot) analysis with monoclonal antibodies reactive with HemA revealed that heme limitation results in a corresponding increase in the abundance of the enzyme. Similar regulation was also observed for E. coli. The near absence of regulation of hemA-lac operon fusions suggested a posttranscriptional control. We report here the results of pulse-labeling and immunoprecipitation studies of this regulation. The principal mechanism that contributes to elevated HemA abundance is protein stabilization. The half-life of HemA protein is approximately 20 min in unrestricted cells but increases to >300 min in heme-limited cells. Similar regulation was observed for a HemA-LacZ hybrid protein containing almost all of the HemA protein (416 residues). Sodium azide prevents HemA turnover in vivo, suggesting a role for energy-dependent proteolysis. This was confirmed by the finding that HemA turnover is completely blocked in a lon clpP double mutant of E. coli. Each single mutant shows only a small effect. The ClpA chaperone, but not ClpX, is required for ClpP-dependent HemA turnover. A hybrid HemA-LacZ protein containing just 18 amino acids from HemA is also stabilized in the lon clpP double mutant, but this shorter fusion protein is not correctly regulated by heme limitation. We suggest that the 18 N terminal amino acids of HemA may constitute a degradation tag, whose function is conditional and modified by the remainder of the protein in a heme-dependent way. Several models are discussed to explain why the turnover of HemA is promoted by Lon-ClpAP proteolysis only when sufficient heme is available. PMID- 9973349 TI - Characterization of insertions of IS476 and two newly identified insertion sequences, IS1478 and IS1479, in Xanthomonas campestris pv. campestris. AB - Thirty-two plasmid insertion mutants were independently isolated from two strains of Xanthomonas campestris pv. campestris in Taiwan. Of the 32 mutants, 14 (44%), 8 (25%), and 4 (12%) mutants resulted from separate insertions of an IS3 family member, IS476, and two new insertion sequences (IS), IS1478 and IS1479. While IS1478 does not have significant sequence homology with any IS elements in the EMBL/GenBank/DDBJ database, IS1479 demonstrated 73% sequence homology with IS1051 in X. campestris pv. dieffenbachiae, 62% homology with IS52 in Pseudomonas syringae pv. glycinea, and 60% homology with IS5 in Escherichia coli. Based on the predicted transposase sequences as well as the terminal nucleotide sequences, IS1478 by itself constitutes a new subfamily of the widespread IS5 family, whereas IS1479, along with IS1051, IS52, and IS5, belongs to the IS5 subfamily of the IS5 family. All but one of the IS476 insertions had duplications of 4 bp at the target sites without sequence preference and were randomly distributed. An IS476 insertion carried a duplication of 952 bp at the target site. A model for generating these long direct repeats is proposed. Insertions of IS1478 and IS1479, on the other hand, were not random, and IS1478 and IS1479 each showed conservation of PyPuNTTA and PyTAPu sequences (Py is a pyrimidine, Pu is a purine, and N is any nucleotide) for duplications at the target sites. The results of Southern blot hybridization analysis indicated that multiple copies of IS476, IS1478, and IS1479 are present in the genomes of all seven X. campestris pv. campestris strains tested and several X. campestris pathovars. PMID- 9973350 TI - Impact of either elevated or decreased levels of cytochrome bd expression on Shigella flexneri virulence. AB - Shigella spp. are the major cause of bacillary dysentery worldwide. The pathogenic process involves bacterial invasion and lysis of the phagocytic vacuole, followed by replication and movement within the cell cytoplasm and, ultimately, spread directly into adjacent cells. This study demonstrates that S. flexneri cytochrome bd expression is necessary for normal intracellular survival and virulence. Cytochrome bd is one of two terminal oxidases in the bacterial respiratory chain that reduce molecular oxygen to water, utilizing intermediates shuttled through the electron transport chain. S. flexneri mutants that contain a disruption in the cydC locus, which leads to defective cytochrome bd expression, or in the riboflavin (ribE) or ubiquinol-8 (ubiH) biosynthetic pathway, which leads to elevated cytochrome bd expression, were evaluated in intracellular survival and virulence assays. The cydC mutant formed significantly smaller plaques, had significantly decreased intracellular survival, and had a 100-fold increase in lethal dose for mice compared with the wild type. The ribE and ubiH mutants each formed significantly larger plaques and had a 10-fold decrease in lethal dose for mice compared with the wild type. The data indicate that expression of cytochrome bd is required for S. flexneri intracellular survival and virulence. PMID- 9973351 TI - Identification and characterization of a two-component sensor-kinase and response regulator system (DcuS-DcuR) controlling gene expression in response to C4 dicarboxylates in Escherichia coli. AB - The dcuB gene of Escherichia coli encodes an anaerobic C4-dicarboxylate transporter that is induced anaerobically by FNR, activated by the cyclic AMP receptor protein, and repressed in the presence of nitrate by NarL. In addition, dcuB expression is strongly induced by C4-dicarboxylates, suggesting the presence of a novel C4-dicarboxylate-responsive regulator in E. coli. This paper describes the isolation of a Tn10 mutant in which the 160-fold induction of dcuB expression by C4-dicarboxylates is absent. The corresponding Tn10 mutation resides in the yjdH gene, which is adjacent to the yjdG gene and close to the dcuB gene at approximately 93.5 min in the E. coli chromosome. The yjdHG genes (redesignated dcuSR) appear to constitute an operon encoding a two-component sensor-regulator system (DcuS-DcuR). A plasmid carrying the dcuSR operon restored the C4 dicarboxylate inducibility of dcuB expression in the dcuS mutant to levels exceeding those of the dcuS+ strain by approximately 1.8-fold. The dcuS mutation affected the expression of other genes with roles in C4-dicarboxylate transport or metabolism. Expression of the fumarate reductase (frdABCD) operon and the aerobic C4-dicarboxylate transporter (dctA) gene were induced 22- and 4-fold, respectively, by the DcuS-DcuR system in the presence of C4-dicarboxylates. Surprisingly, anaerobic fumarate respiratory growth of the dcuS mutant was normal. However, under aerobic conditions with C4-dicarboxylates as sole carbon sources, the mutant exhibited a growth defect resembling that of a dctA mutant. Studies employing a dcuA dcuB dcuC triple mutant unable to transport C4 dicarboxylates anaerobically revealed that C4-dicarboxylate transport is not required for C4-dicarboxylate-responsive gene regulation. This suggests that the DcuS-DcuR system responds to external substrates. Accordingly, topology studies using 14 DcuS-BlaM fusions showed that DcuS contains two putative transmembrane helices flanking a approximately 140-residue N-terminal domain apparently located in the periplasm. This topology strongly suggests that the periplasmic loop of DcuS serves as a C4-dicarboxylate sensor. The cytosolic region of DcuS (residues 203 to 543) contains two domains: a central PAS domain possibly acting as a second sensory domain and a C-terminal transmitter domain. Database searches showed that DcuS and DcuR are closely related to a subgroup of two-component sensor-regulators that includes the citrate-responsive CitA-CitB system of Klebsiella pneumoniae. DcuS is not closely related to the C4-dicarboxylate sensing DctS or DctB protein of Rhodobacter capsulatus or rhizobial species, respectively. Although all three proteins have similar topologies and functions, and all are members of the two-component sensor-kinase family, their periplasmic domains appear to have evolved independently. PMID- 9973352 TI - Inhibition of homologous recombination by the plasmid MucA'B complex. AB - By its functional interaction with a RecA polymer, the mutagenic UmuD'C complex possesses an antirecombination activity. We show here that MucA'B, a functional homolog of the UmuD'C complex, inhibits homologous recombination as well. In F- recipients expressing MucA'B from a Ptac promoter, Hfr x F- recombination decreased with increasing MucA'B concentrations down to 50-fold. In damage induced pKM101-containing cells expressing MucA'B from the native promoter, recombination between a UV-damaged F lac plasmid and homologous chromosomal DNA decreased 10-fold. Overexpression of MucA'B together with UmuD'C resulted in a synergistic inhibition of recombination. RecA[UmuR] proteins, which are resistant to UmuD'C inhibition of recombination, are inhibited by MucA'B while promoting MucA'B-promoted mutagenesis efficiently. The data suggest that MucA'B and UmuD'C contact a RecA polymer at distinct sites. The MucA'B complex was more active than UmuD'C in promoting UV mutagenesis, yet it did not inhibit recombination more than UmuD'C does. The enhanced mutagenic potential of MucA'B may result from its inherent superior capacity to assist DNA polymerase in trans-lesion synthesis. In the course of this work, we found that the natural plasmid pKM101 expresses around 45,000 MucA and 13,000 MucB molecules per lexA(Def) cell devoid of LexA. These molecular Muc concentrations are far above those of the chromosomally encoded Umu counterparts. Plasmid pKM101 belongs to a family of broad-host-range conjugative plasmids. The elevated levels of the Muc proteins might be required for successful installation of pKM101-like plasmids into a variety of host cells. PMID- 9973353 TI - Purification, characterization, and cloning of a eubacterial 3-hydroxy-3 methylglutaryl coenzyme A reductase, a key enzyme involved in biosynthesis of terpenoids. AB - The eubacterial 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase (EC 1.1.1.34) was purified 3,000-fold from Streptomyces sp. strain CL190 to apparent homogeneity with an overall yield of 2.1%. The purification procedure consisted of (NH4)2SO4 precipitation, heat treatment and anion exchange, hydrophobic interaction, and affinity chromatographies. The molecular mass of the enzyme was estimated to be 41 kDa by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and 100 to 105 kDa by gel filtration chromatography, suggesting that the enzyme is most likely to be a dimer. The enzyme showed a pH optimum of around 7.2, with apparent Km values of 62 microM for NADPH and 7.7 microM for HMG CoA. A gene from CL190 responsible for HMG-CoA reductase was cloned by the colony hybridization method with an oligonucleotide probe synthesized on the basis of the N-terminal sequence of the purified enzyme. The amino acid sequence of the CL190 HMG-CoA reductase revealed several limited motifs which were highly conserved and common to the eucaryotic and archaebacterial enzymes. These sequence conservations suggest a strong evolutionary pressure to maintain amino acid residues at specific positions, indicating that the conserved motifs might play important roles in the structural conformation and/or catalytic properties of the enzyme. PMID- 9973354 TI - Analysis of rpoS mRNA in Salmonella dublin: identification of multiple transcripts with growth-phase-dependent variation in transcript stability. AB - In Salmonella dublin, rpoS encodes an alternative sigma factor of the RNA polymerase that activates a variety of stationary-phase-induced genes, including some virulence-associated genes. In this work, we studied the regulation and transcriptional organization of rpoS during growth. We found two transcripts, 2.3 and 1.6 kb in length, that represent the complete rpoS sequence. The 2.3-kb transcript is a polycistronic message that also includes the upstream nlpD gene. It is driven by a weak promoter with increasing activity when cells enter early stationary growth. The 1.6-kb message includes 566 bp upstream of the rpoS start codon. It is transcribed from a strong sigma70 RNA polymerase-dependent promoter which is independent of growth. The decay of this transcript decreases substantially in early stationary growth, resulting in a significant net increase in rpoS mRNA levels. These levels are approximately 10-fold higher than the levels of the 2.3-kb mRNA, indicating that the 1.6-kb message is mainly responsible for RpoS upregulation. In addition to the 2.3- and 1.6-kb transcripts, two smaller 1.0- and 0.4-kb RNA species are produced from the nlpD rpoS locus. They do not allow translation of full-length RpoS; hence their significance for rpoS regulation remains unclear. We conclude that of four transcripts arising from the nlpD-rpoS locus, only one plays a significant role in rpoS expression in S. dublin. Its upregulation when cells enter stationary growth is due primarily to an increase in transcript stability. PMID- 9973355 TI - Functional determinants of the Escherichia coli fis promoter: roles of -35, -10, and transcription initiation regions in the response to stringent control and growth phase-dependent regulation. AB - Escherichia coli Fis is a small DNA binding and bending protein that has been implicated in a variety of biological processes. A minimal promoter sequence consisting of 43 bp is sufficient to generate its characteristic growth phase dependent expression pattern and is also subject to negative regulation by stringent control. However, information about the precise identification of nucleotides contributing to basal promoter activity and its regulation has been scant. In this work, 72 independent mutations were generated in the fis promoter (fis P) region from -108 to +78 using both random and site-directed PCR mutagenesis. beta-Galactosidase activities from mutant promoters fused to the (trp-lac)W200 fusion on a plasmid were used to conclusively identify the sequences TTTCAT and TAATAT as the -35 and -10 regions, respectively, which are optimally separated by 17 bp. We found that four consecutive substitutions within the GC-rich sequence just upstream of +1 and mutations in the -35 region, but not in the -10 region, significantly reduced the response to stringent control. Analysis of the effects of mutations on growth phase-dependent regulation showed that replacing the predominant transcription initiation nucleotide +1C with a preferred nucleotide (A or G) profoundly altered expression such that high levels of fis P mRNA were detected during late logarithmic and early stationary phases. A less dramatic effect was seen with improvements in the -10 and -35 consensus sequences. These results suggest that the acute growth phase-dependent regulation pattern observed with this promoter requires an inefficient transcription initiation process that is achieved with promoter sequences deviating from the 10 and -35 consensus sequences and, more importantly, a dependence upon the availability of the least favored transcription initiation nucleotide, CTP. PMID- 9973356 TI - Molecular cloning, sequencing, purification, and characterization of Pseudomonas aeruginosa ribosome recycling factor. AB - Ribosome recycling factor (RRF) is required for release of 70S ribosomes from mRNA on reaching the termination codon for the next cycle of protein synthesis. The RRF-encoding gene (frr) of Pseudomonas aeruginosa PAO1 was functionally cloned by using a temperature-sensitive frr mutant of Escherichia coli and sequenced. The P. aeruginosa frr was mapped at 30 to 32 min of the P. aeruginosa chromosome. The deduced amino acid sequence of RRF showed a 64% identity to that of E. coli RRF. In an assay including E. coli polysome and elongation factor G, purified recombinant RRF of P. aeruginosa released monosomes from polysomes. This is the first case in which an RRF homologue was found to be active in heterogeneous ribosome recycling machinery. The genes for ribosomal protein S2 (rpsB), elongation factor Ts (tsf), and UMP kinase (pyrH) are located upstream of frr. The arrangement of the genes, rpsB-tsf-pyrH-frr, resembles those reported for E. coli and Bacillus subtilis. Even in the cyanobacterium genome, the arrangement pyrH-frr is conserved. Although RRF homologues are found in eukaryotic cells, phylogenetic analysis suggests that they were originally present within the members of the phylogenetic tree of prokaryotic RRF. This finding suggests that the ribosome recycling step catalyzed by RRF is specific for prokaryotic cells and that eukaryotic RRF is required for protein synthesis in organelles, which are believed to be phylogenetically originated from prokaryotes. PMID- 9973357 TI - Rapid purification and properties of betaine aldehyde dehydrogenase from Pseudomonas aeruginosa. AB - Betaine aldehyde dehydrogenase (BADH) (EC 1.2.1.8) catalyzes the last, irreversible step in the synthesis of the osmoprotectant glycine betaine from choline. In Pseudomonas aeruginosa this reaction is also an obligatory step in the assimilation of carbon and nitrogen when bacteria are growing in choline or choline precursors. We present here a method for the rapid purification to homogeneity of this enzyme by the use of ion-exchange and affinity chromatographies on 2',5'-ADP-Sepharose, which results in a high yield of pure enzyme with a specific activity at 30 degreesC and pH 7.4 of 74.5 U/mg of protein. Analytical ultracentrifugation, gel filtration, chemical cross-linking, and sodium dodecyl sulfate-polyacrylamide gel electrophoresis suggest that BADH from P. aeruginosa is a homodimer with 61-kDa subunits. The amino acid composition and the N-terminal sequence of 21 amino acid residues showed significant similarity with those of the enzymes from Xanthomonas translucens and Escherichia coli. Neither BADH activity nor BADH protein was found in cell extracts from bacteria grown in the absence of choline. In contrast to other BADHs studied to date, the Pseudomonas enzyme cannot use positively charged aldehydes other than betaine aldehyde as substrates. The oxidation reaction has an activation energy of 39.8 kJ mol-1. The pH dependence of the velocity indicated an optimum at pH 8.0 to 8.5 and the existence of two ionizable groups with macroscopic pK values of 7.0 +/- 0.1 and 9. 7 +/- 0.1 involved in catalysis and/or binding of substrates. The enzyme is inactivated at 40 degreesC, but activity is regained when the heated enzyme is cooled to 30 degreesC or lower. At the optimum pH of 8.0, the enzyme is inactivated by dilution, but it is stable at pH 6.5 even at very low concentrations. Also, P. aeruginosa BADH activity is rapidly lost on removal of K+. In all cases studied, inactivation involves a biphasic process, which was dependent on the enzyme concentration only in the case of inactivation by dilution. NADP+ considerably protected the enzyme against these inactivating conditions. PMID- 9973358 TI - Analysis of the type 1 pilin gene cluster fim in Salmonella: its distinct evolutionary histories in the 5' and 3' regions. AB - The type 1 pilin encoded by fim is present in both Escherichia coli and Salmonella natural isolates, but several lines of evidence indicate that similarities at the fim locus may be an example of independent acquisition rather than common ancestry. For example, the fim gene cluster is found at different chromosomal locations and with distinct gene orders in these closely related species. In this work we examined the fim gene cluster of Salmonella, the genes of which show high nucleotide sequence divergence from their E. coli counterparts, as well as a different G+C content and codon usage. DNA hybridization analysis revealed that, among the salmonellae, the fim gene cluster is present in all isolates of S. enterica but is absent from S. bongori. Molecular phylogenetic analyses of the fimA and fimI genes yield an estimate of phylogeny that is in satisfactory congruence with housekeeping and other virulence genes examined in this species. In contrast, phylogenetic analyses of the fimZ, fimY, and fimW genes indicate that horizontal transfer of this region has occurred more than once. There is also size variation in the fimZ, fimY, and fimW intergenic regions in the 3' region, and these genes are absent in isolate S2983 of subspecies IIIa. Interestingly, the G+C contents of the fimZ, fimY, and fimW genes are less than 46%, which is considerably lower than those of the other six genes of the fim cluster. This study demonstrates that horizontal transmission of all or part of the same gene cluster can occur repeatedly, with the result that different regions of a single gene cluster may have different evolutionary histories. PMID- 9973360 TI - IS1634, a novel insertion element creating long, variable-length direct repeats which is specific for Mycoplasma mycoides subsp. mycoides small-colony type. AB - A new insertion sequence, IS1634, has been identified in Mycoplasma mycoides subsp. mycoides small-colony type (SC). IS1634 shows structural and functional similarities to IS1549 of Mycobacterium smegmatis and with it seems to form a new class or family of insertion sequences. IS1634 has a size of 1,872 bp, including two 13-bp terminal inverted repeats. It contains an open reading frame (ORF) encoding a product of 533 amino acids which shows similarity to the transposase of IS1549 and to a lesser extent to the transposases of IS elements of the IS4 family. IS1634 is present at about 30 copies in the genome of all 22 different field strains of M. mycoides subsp. mycoides SC tested. Characteristic of IS1634 are the long and variable-length direct repeats at the sites of insertion which were found to reach up to about 500 bp. IS1634 is specific to M. mycoides subsp. mycoides SC and is not present in any of the other members of the M. mycoides cluster. Neither was it found in other closely related Mycoplasma species of ruminants. PMID- 9973359 TI - Conversion of 3-chlorocatechol by various catechol 2,3-dioxygenases and sequence analysis of the chlorocatechol dioxygenase region of Pseudomonas putida GJ31. AB - Pseudomonas putida GJ31 contains an unusual catechol 2,3-dioxygenase that converts 3-chlorocatechol and 3-methylcatechol, which enables the organism to use both chloroaromatics and methylaromatics for growth. A 3.1-kb region of genomic DNA of strain GJ31 containing the gene for this chlorocatechol 2,3-dioxygenase (cbzE) was cloned and sequenced. The cbzE gene appeared to be plasmid localized and was found in a region that also harbors genes encoding a transposase, a ferredoxin that was homologous to XylT, an open reading frame with similarity to a protein of a meta-cleavage pathway with unknown function, and a 2 hydroxymuconic semialdehyde dehydrogenase. CbzE was most similar to catechol 2,3 dioxygenases of the 2.C subfamily of type 1 extradiol dioxygenases (L. D. Eltis and J. T. Bolin, J. Bacteriol. 178:5930-5937, 1996). The substrate range and turnover capacity with 3-chlorocatechol were determined for CbzE and four related catechol 2,3-dioxygenases. The results showed that CbzE was the only enzyme that could productively convert 3-chlorocatechol. Besides, CbzE was less susceptible to inactivation by methylated catechols. Hybrid enzymes that were made of CzbE and the catechol 2, 3-dioxygenase of P. putida UCC2 (TdnC) showed that the resistance of CbzE to suicide inactivation and its substrate specificity were mainly determined by the C-terminal region of the protein. PMID- 9973361 TI - The Enterococcus faecalis pyr operon is regulated by autogenous transcriptional attenuation at a single site in the 5' leader. AB - The 5' end of the Enterococcus faecalis pyr operon specifies, in order, the promoter, a 5' untranslated leader, the pyrR gene encoding the regulatory protein for the operon, a 39-nucleotide (nt) intercistronic region, the pyrP gene encoding a uracil permease, a 13-nt intercistronic region, and the pyrB gene encoding aspartate transcarbamylase. The 5' leader RNA is capable of forming stem loop structures involved in attenuation control of the operon. No attenuation regions, such as those found in the Bacillus subtilis pyr operon, are present in the pyrR-pyrP or pyrP-pyrB intercistronic regions. Several lines of evidence demonstrate that the E. faecalis pyr operon is repressed by uracil via transcriptional attenuation at the single 5' leader termination site and that attenuation is mediated by the PyrR protein. PMID- 9973362 TI - sn-glycerol-1-phosphate-forming activities in Archaea: separation of archaeal phospholipid biosynthesis and glycerol catabolism by glycerophosphate enantiomers. AB - In Methanobacterium thermoautotrophicum, sn-glycerol-1-phosphate (G-1-P) dehydrogenase is responsible for the formation of the Archaea-specific backbone of phospholipids, G-1-P, from dihydroxyacetonephosphate (DHAP). The possible G-1 P-forming activities were surveyed in cell-free extracts of six species of Archaea. All the archaeal cell-free homogenates tested revealed the ability to form G-1-P from DHAP. In addition, activities of G-3-P-forming glycerol kinase and G-3-P dehydrogenase were also detected in four heterotrophic archaea, while glycerol kinase activity was not detected in two autotrophic methanogens. These results show that G-1-P is produced from DHAP by G-1-P dehydrogenase in a wide variety of archaea while exogenous glycerol is catabolized via G-3-P. PMID- 9973363 TI - Specific effects of a recB mutation on the HfrH strain of Escherichia coli. AB - The recB268::Tn10 mutation was introduced into the HfrH strain of Escherichia coli. Compared with recB F- and recB F+ cells, the viability of this mutant strain was much lower. Compared with wild-type HfrH, the recB derivative donated much shorter fragments of its chromosome to the recipient. It is suggested that the recB gene product (i.e., RecBCD enzyme) participates in Hfr transfer. PMID- 9973364 TI - Auxins upregulate expression of the indole-3-pyruvate decarboxylase gene in Azospirillum brasilense. AB - Transcription of the Azospirillum brasilense ipdC gene, encoding an indole-3 pyruvate decarboxylase involved in the biosynthesis of indole-3-acetic acid (IAA), is induced by IAA as determined by ipdC-gusA expression studies and Northern analysis. Besides IAA, exogenously added synthetic auxins such as 1 naphthaleneacetic acid, 2,4-dichlorophenoxypropionic acid, and p chlorophenoxyacetic acid were also found to upregulate ipdC expression. No upregulation was observed with tryptophan, acetic acid, or propionic acid or with the IAA conjugates IAA ethyl ester and IAA-L-phenylalanine, indicating structural specificity is required for ipdC induction. This is the first report describing the induction of a bacterial gene by auxin. PMID- 9973365 TI - Cloning and characterization of arylamine N-acetyltransferase genes from Mycobacterium smegmatis and Mycobacterium tuberculosis: increased expression results in isoniazid resistance. AB - Arylamine N-acetyltransferases (NATs) are found in many eukaryotic organisms, including humans, and have previously been identified in the prokaryote Salmonella typhimurium. NATs from many sources acetylate the antitubercular drug isoniazid and so inactivate it. nat genes were cloned from Mycobacterium smegmatis and Mycobacterium tuberculosis, and expressed in Escherichia coli and M. smegmatis. The induced M. smegmatis NAT catalyzes the acetylation of isoniazid. A monospecific antiserum raised against pure NAT from S. typhimurium recognizes NAT from M. smegmatis and cross-reacts with recombinant NAT from M. tuberculosis. Overexpression of mycobacterial nat genes in E. coli results in predominantly insoluble recombinant protein; however, with M. smegmatis as the host using the vector pACE-1, NAT proteins from M. tuberculosis and M. smegmatis are soluble. M. smegmatis transformants induced to express the M. tuberculosis nat gene in culture demonstrated a threefold higher resistance to isoniazid. We propose that NAT in mycobacteria could have a role in acetylating, and hence inactivating, isoniazid. PMID- 9973367 TI - Bacteriophage T4 gp2 interferes with cell viability and with bacteriophage lambda Red recombination. AB - The T4 head protein, gp2, promotes head-tail joining during phage morphogenesis and is also incorporated into the phage head. It protects the injected DNA from degradation by exonuclease V during the subsequent infection. In this study, we show that recombinant gp2, a very basic protein, rapidly kills the cells in which it is expressed. To further illustrate the protectiveness of gp2 for DNA termini, we compare the effect of gp2 expression on Red-mediated and Int-mediated recombination. Red-mediated recombination is nonspecific and requires the transient formation of double-stranded DNA termini. Int-mediated recombination, on the other hand, is site specific and does not require chromosomal termini. Red mediated recombination is inhibited to a much greater extent than is Int-mediated recombination. We conclude from the results of these physiological and genetic experiments that T4 gp2 expression, like Mu Gam expression, kills bacteria by binding to double-stranded DNA termini, the most likely mode for its protection of entering phage DNA from exonuclease V. PMID- 9973366 TI - The lethal effect of a benzamide derivative, 3-methoxybenzamide, can be suppressed by mutations within a cell division gene, ftsZ, in Bacillus subtilis. AB - 3-Methoxybenzamide (3-MBA), which is known to be an inhibitor of ADP ribosyltransferase, inhibits cell division in Bacillus subtilis, leading to filamentation and eventually lysis of cells. Our genetic analysis of 3-MBA resistant mutants indicated that the primary target of the drug is the cell division system involving FtsZ function during both vegetative growth and sporulation. PMID- 9973368 TI - Cell surface galactosylation is essential for nonsexual flocculation in Schizosaccharomyces pombe. AB - We have isolated fission yeast mutants that constitutively flocculate upon growth in liquid media. One of these mutants, the gsf1 mutant, was found to cause dominant, nonsexual, and calcium-dependent aggregation of cells into flocs. Its flocculation was inhibited by the addition of galactose but was not affected by the addition of mannose or glucose, unlike Saccharomyces cerevisiae FLO mutants. The gsf1 mutant coflocculated with Schizosaccharomyces pombe wild-type cells, while no coflocculation was found with galactose-deficient (gms1Delta) cells. Moreover, flocculation of the gsf1 mutant was also inhibited by addition of cell wall galactomannan from wild-type cells but not from gms1Delta cells. These results suggested that galactose residues in the cell wall glycoproteins may be receptors of gsf1-mediated flocculation, and therefore cell surface galactosylation is required for nonsexual flocculation in S. pombe. PMID- 9973369 TI - Chromosomal changes during experimental evolution in laboratory populations of Escherichia coli. AB - Short-term rates of chromosome evolution were analyzed in experimental populations of Escherichia coli B that had been propagated for 2,000 generations under four thermal regimens. Chromosome alterations were monitored in 24 independent populations by pulsed-field gel electrophoresis of DNA treated with five rare-cutting restriction enzymes. A total of 11 changes, 8 affecting chromosome size and 3 altering restriction sites, were observed in these populations, with none occurring in strains cultured at 37 degreesC. Considering the changes detected in these experimental populations, the rate of chromosome alteration of E. coli is estimated to be half of that observed in experimental populations of yeast. PMID- 9973370 TI - The virulence plasmid of Salmonella typhimurium is self-transmissible. AB - Most isolates of Salmonella enterica serovar Typhimurium contain a 90-kb virulence plasmid. This plasmid is reported to be mobilizable but nonconjugative. However, we have determined that the virulence plasmid of strains LT2, 14028, and SR-11 is indeed self-transmissible. The plasmid of strain SL1344 is not. Optimal conjugation frequency requires filter matings on M9 minimal glucose plates with a recipient strain lacking the virulence plasmid. These conditions result in a frequency of 2.9 x 10(-4) transconjugants/donor. Matings on Luria-Bertani plates, liquid matings, or matings with a recipient strain carrying the virulence plasmid reduce the efficiency by up to 400-fold. Homologs of the F plasmid conjugation genes are physically located on the virulence plasmid and are required for the conjugative phenotype. PMID- 9973371 TI - Lack of genetic differentiation between two geographically diverse samples of Candida albicans isolated from patients infected with human immunodeficiency virus. AB - The patterns of genetic variation of samples of Candida albicans isolated from patients infected with human immunodeficiency virus in Durham, N.C., and Vitoria, Brazil, were compared. Genotypes for 126 strains were obtained at 16 polymorphic restriction sites distributed on nine PCR fragments. The results indicated evidence of clonality both within and between these two geographically diverse samples. The samples are genetically very similar, with little evidence of genetic differentiation. PMID- 9973373 TI - Cutting edge: dominant effect of Ile50Val variant of the human IL-4 receptor alpha-chain in IgE synthesis. AB - Two variants of the IL-4R alpha-chain (IL-4Ralpha) gene have been recently identified in association with different atopic disorders. To clarify the etiological relationship between the two variants, we analyzed responsiveness to IL-4 of transfectants with four kinds of IL-4Ralpha carrying either Val or Ile at 50 and either Gln or Arg at 551. The substitution of Ile for Val augmented STAT6 activation, proliferation, and transcription activity of the Iepsilon promoter by IL-4, whereas that of Arg for Gln did not change these IL-4 signals. Arg551 was not associated with atopic asthma in the Japanese population. CD23 expression and IgE synthesis by IL-4 were augmented in Ile50-bearing PBMC, compared with those bearing Val50. Taken together, substitution of Arg551 does not enhance the IL-4 signal for generation of germline epsilon transcript, whereas the substitution of Ile50 contributes to enhancement of IgE synthesis. PMID- 9973372 TI - Cutting edge: MHC class I triggering by a novel cell surface ligand costimulates proliferation of activated human T cells. AB - BY55 is a human cell surface molecule whose expression is restricted to NK cells, a subset of circulating CD8+ T lymphocytes, and all intestinal intraepithelial T lymphocytes. Here, we report that BY55 is a novel NK receptor showing broad specificity for both classical and nonclassical MHC class I molecules, and that optimal binding requires a prior aggregation of MHC class I complexes. Using BY55 transfectants, we have identified functional consequences of MHC class I/ligand interactions for the class I-bearing cell. The triggering of MHC class I molecules on human T cell clones by BY55 delivered a potent proliferative signal in the presence of soluble CD3 mAb. The costimulatory signal provided by MHC class I ligation was only seen in activated, and not resting, peripheral blood T cells. This observation represents an additional and/or alternative pathway to CD28 costimulation and may be of particular relevance in memory T cells lacking CD28, such as intestinal intraepithelial T lymphocytes, which are CD28- but BY55+. PMID- 9973374 TI - Cutting edge: coordinate regulation of IFN regulatory factor-1 and the polymeric Ig receptor by proinflammatory cytokines. AB - The polymeric IgR (pIgR) mediates transcytosis of IgA across epithelial barriers of mucous membranes and exocrine glands. Synthesis of pIgR is up-regulated by the proinflammatory cytokines TNF-alpha, IFN-gamma, and IL-1 in HT-29 human colon carcinoma cells. We previously reported that IFN-gamma and TNF-alpha induce production of the transcription factor IFN regulatory factor-1 (IRF-1) in HT-29 cells and that IRF-1 binds to an element in exon 1 of the PIGR gene. We now report that levels of IRF-1 and pIgR mRNA are coordinately regulated in HT-29 cells by TNF-alpha, IFN-gamma, and IL-1beta. Furthermore, we demonstrate that in vivo expression of pIgR mRNA is greatly depressed in the intestine and liver of IRF-1-deficient mice. Our findings indicate a major role for the IRF-1 transcription factor in regulation of the PIGR gene and suggest a model for regulation of important genes in the mucosal immune system by proinflammatory cytokines. PMID- 9973375 TI - Antigen-induced coreceptor down-regulation on thymocytes is not a result of apoptosis. AB - The various stages of T cell development are typically characterized by the expression level of the two coreceptors, CD4 and CD8. During the CD4+CD8+ (double positive, DP) stage of development, thymocytes that perceive a low avidity signal through the TCR go on to differentiate (positive selection), and ultimately down regulate one coreceptor to express either CD4 or CD8. Alternatively, thymocytes that perceive a high avidity signal down-regulate both coreceptors and are induced to die via apoptosis (negative selection). However, it has recently been suggested that positively selected thymocytes may also partially down-regulate both coreceptors before up-regulating the one coreceptor that is ultimately expressed. This would imply that coreceptor down-regulation (dulling) is not a consequence of commitment to the death pathway. To explore this possibility, we have utilized an in vitro assay to demonstrate that dulling occurred in response to both positive and negative selecting ligands in vitro, was not a result of nonspecific membrane perturbation, was not dependent on the type of APC, and occurred before death in vitro. Furthermore, when thymocyte apoptosis was blocked, CD4 and CD8 were down-regulated in response to TCR stimulation. These data suggest that dulling in response to TCR ligation is distinct from death, and support a model in which DP dulling occurs during both positive and negative selection. The biological implications of this phenomenon are discussed. PMID- 9973376 TI - IL-17 is produced by some proinflammatory Th1/Th0 cells but not by Th2 cells. AB - IL-17 is defined as a proinflammatory cytokine and produced by activated CD4+ T cells. In rheumatoid arthritis synovial tissue, high levels of IL-17 contribute to IL-6 production by synoviocytes. The present study was performed to see whether Th cells that produce IL-17 are associated with the Th1, Th2, or Th0 subset. Thirty-three CD4+, alphabeta+ T cell clones were developed from synovial membranes and synovial fluid of rheumatoid arthritis patients. Thirteen clones were defined as Th1 since they produced IFN-gamma but not IL-4, and four clones were defined as Th0 type that produced both IL-4 and IFN-gamma. Sixteen clones were defined as Th2 since they produced high levels of IL-4 and/or IL-10 but not IFN-gamma. IL-17 was measured in a bioassay, where IL-6 production from synoviocytes was a measurement for IL-17 activity in the presence and absence of blocking anti-IL-17 mAb. Three Th1 clones and two Th0 clones produced IL-17. In contrast, none of the sixteen Th2 clones analyzed produced IL-17. In addition, six Th2 clones were further cultured in conditions that induced a switch to Th1 type. Induction of this Th1 phenotype also led to production of IL-17 in two of these clones. The results demonstrate that some cells of the Th1/Th0 phenotype produce IL-17 but not cells of the Th2 phenotype. Thus, IL-17 may define a new subset of T cells, and IL-17 production appears to be a mechanism for Th1/Th0 cells, the most frequent Th subtype present in the rheumatoid synovium, to contribute to the local inflammatory reactions. PMID- 9973377 TI - CD4-mediated inhibiton of IL-2 production in activated T cells. AB - The role of CD4 in T cell activation has been attributed to its capacity to increase the avidity of interaction with APC and to shuttle associated Lck to the TCR/CD3 activation complex. The results presented in this study demonstrate that ligation of CD4 inhibits ongoing responses of preactivated T cells. Specifically, delayed addition of CD4-specific mAb is shown to inhibit Ag- or mAb-induced responses of both primary T cells and T cell clonal variants. The Ag responses of the latter are independent of the adhesion provided by CD4; thus the observed inhibition is not due to blocking CD4-MHC interactions. Further, analysis of the clonal variants demonstrates that CD4-associated Lck is not essential for the inhibition observed, as anti-CD4 inhibits responses of clonal variants, expressing a form of CD4 unable to associate with Lck (double cysteine-mutated CD4). The inhibition is counteracted by the addition of exogenous IL-2, demonstrating that the block is not due to a lesion in IL-2 utilization, rather its production. It is demonstrated that the delayed addition of anti-CD4 results in a rapid reduction in steady-state levels of IL-2 mRNA in both primary T cells and clonal variants. PMID- 9973378 TI - IL-4 selectively inhibits IL-2-triggered Stat5 activation, but not proliferation, in human T cells. AB - IL-2 activates several distinct signaling pathways that are important for T cell activation, proliferation, and differentiation into both Th1 and Th2 phenotypes. IL-4, the major cytokine that promotes differentiation of Th2 cells, has been shown to block signaling of the Th1-promoting cytokine IL-12. As IL-2 synergizes with IL-12 in promoting Th1 differentiation, the effects of IL-4 on IL-2 signal transduction were investigated. IL-4 suppressed activation of DNA binding and tyrosine phosphorylation of the transcription factor Stat5 by IL-2, and suppressed the expression of the IL-2-inducible genes CD25, CIS, the PGE2 receptor, and cytokine responsive (CR) genes CR1 and CR8. Activation of Stat5 by cytokines that share a common gamma receptor subunit, IL-2, IL-7, and IL-15, was suppressed by preculture in IL-4. Activation of the Jak1 and Jak3 kinases that are proximal to Stat5 in the IL-2-Jak-STAT signaling pathway was suppressed, and this correlated with inhibition of IL-2Rbeta subunit expression. In contrast to suppression of Stat5, proliferative responses to IL-2 were augmented in IL-4 cultured cells, and activation of proliferative pathways leading to activation of mitogen activated protein kinases, induction of expression of Myc, Fos, Pim-1, and cyclin D3, and decreased levels of the cyclin-dependent kinase inhibitor p27 were intact. These results identify molecular mechanisms underlying interactions between IL-4 and IL-2 in T cells and demonstrate that one mechanism of regulation of IL-2 activity is selective and differential modulation of signaling pathways. PMID- 9973379 TI - Regulation of cytotoxic T lymphocyte-associated molecule-4 by Src kinases. AB - Cytotoxic T lymphocyte-associated molecule-4 (CTLA-4) is a cell surface receptor expressed on activated T cells that can inhibit T cell responses induced by activation of the TCR and CD28. Studies with phosphorylated peptides based on the CTLA-4 intracellular domain have suggested that tyrosine phosphorylation of CTLA 4 may regulate its interactions with cytoplasmic proteins that could determine its intracellular trafficking and/or signal transduction. However, the kinase(s) that phosphorylate CTLA-4 remain uncharacterized. In this report, we show that CTLA-4 can associate with the Src kinases Fyn and Lck and that transfection of Fyn or Lck, but not the unrelated kinase ZAP70, can induce tyrosine phosphorylation of CTLA-4 on residues Y201 and Y218. A similar pattern of tyrosine phosphorylation was found in pervanadate-treated Jurkat T cells stably expressing CTLA-4. Phosphorylation of CTLA-4 Y201 in Jurkat cells correlated with cell surface accumulation of CTLA-4. CTLA-4 phosphorylation induced the association of CTLA-4 with the tyrosine phosphatase SHP-2, but not with phosphatidylinositol 3-kinase. In contrast, Lck-induced phosphorylation of CD28 resulted in the recruitment of phosphatidylinositol 3-kinase, but not SHP-2. These findings suggest that phosphorylation of CD28 and CTLA-4 by Lck activates distinct intracellular signaling pathways. The association of CTLA-4 with Src kinases and with SHP-2 results in the formation of a CTLA-4 complex with the potential to regulate T cell activation. PMID- 9973381 TI - Processing and release of IL-16 from CD4+ but not CD8+ T cells is activation dependent. AB - IL-16 is synthesized as a precursor molecule of 68 kDa (pro-IL-16) that is processed by caspase-3, a member of the IL-1 converting enzyme (ICE) family. This cleavage results in a 13-kDa carboxy terminal peptide, which constitutes the bioactive secreted form of IL-16. We have previously reported constitutive IL-16 mRNA expression and pro-IL-16 protein in CD4+ and CD8+ T cells. Although bioactive IL-16 protein is present in unstimulated CD8+ T cells, there is no bioactive IL-16 present in CD4+ T cells. Along these lines, unstimulated CD8+ T cells contain active caspase-3. In the current studies we investigated the regulation of IL-16 protein and mRNA expression in CD4+ T cells and determined the kinetics of secretion following stimulation of the TCR. CD4+ T cells release IL-16 protein following antigenic stimulation, and this release is accelerated in time by costimulation via CD28. However, CD3/CD28 costimulation did not alter IL 16 mRNA appearance or stability in either CD4+ or CD8+ T cells. The secretion of bioactive IL-16 from CD4+ T cells correlated with the appearance of cleavage of pro-caspase-3 into its 20-kDa active form. Thus, resting CD8+ T cells contain active caspase-3 that is capable of cleaving pro-IL-16, whereas CD4+ T cells require activation for the appearance of active caspase-3. The mechanism of release or secretion of bioactive IL-16 is currently unknown, but does not correlate with cellular apoptosis. PMID- 9973380 TI - Selective expression of a novel surface molecule by human Th2 cells in vivo. AB - The search for reliable marker molecules discriminating between human Th1 and Th2 cells identified a gene encoding a novel member of the G protein-coupled leukocyte chemoattractant receptor family, which is selectively expressed in Th2 but not Th1 lineage cells, thereby named CRTH2 (chemoattractant receptor homologous molecule expressed on Th2 cells). Studies with anti-CRTH2 mAbs demonstrated that CRTH2 was expressed in a small population (0.4-6.5%) of CD4+ T cells in fresh PBMCs of healthy adults, but no remarkable expression was seen in B cells and NK cells. In some cases, CD8+ T cells ( approximately 3.5%) expressed CRTH2. Phenotypes of CD4+ T cells expressing CRTH2 were CD45RA-, CD45RO+, and CD25+, similar to those of Ag-activated effector/memory T cells. Freshly isolated CRTH2+ CD4+ T cells produced Th2- but little or no Th1-type cytokines upon stimulation with PMA and ionomycin. In addition, an allergen-induced proliferative response in fresh PBMCs was significantly and selectively reduced by subtracting CRTH2+ cells. Together, these results indicate that CRTH2 is selectively expressed in vivo in an activated state of Th2 cells including allergen-responsive Th2 cells, suggesting its pivotal roles in ongoing Th2-type immune reactions. PMID- 9973382 TI - Timing and casting for actors of thymic negative selection. AB - We have recently proposed a new model for the differentiation pathway of alphabeta TCR thymocytes, with the CD4 and CD8 coreceptors undergoing an unexpectedly complex series of expression changes. Taking into account this new insight, we reinvestigated the timing of thymic negative selection. We found that, although endogenous superantigen-driven thymic negative selection could occur at different steps during double-positive/single-positive cell transition, this event was never observed among CD4lowCD8low TCRint CD69+ thymocytes, i.e., within the first subset to be generated upon TCR-mediated activation of immature double-positive cells. We confirm a role for CD40/CD40L interaction, and the absence of involvement of CD28 costimulation, in thymic deletion in vivo. Surprisingly, we found that thymic negative selection was impaired in the absence of Fas, but not FasL, molecule expression. Finally, we show involvement in opposing directions for p59fyn and SHP-1 molecules in signaling for thymic negative selection. PMID- 9973383 TI - Isolation of MHC class I-restricted tumor antigen peptide and its precursors associated with heat shock proteins hsp70, hsp90, and gp96. AB - We have previously demonstrated that vaccination with heat shock proteins hsp70, hsp90, and gp96 elicits specific immunity against the tumor from which the hsps were purified. Although the association of tumor Ag peptides with these hsps have been suggested, the identification of the peptides or their precursors stripped from the hsps remained to be resolved. We show in this report that an Ld restricted cytotoxic T lymphocyte epitope of a mouse leukemia RLmale symbol1 and its precursors are associated with the chaperones hsp90 and hsp70 in the cytosol and gp96 in the lumen of the endoplasmic reticulum. Hsp70 was associated with only final sized octamer, while hsp90 was found to associate with the octamer and two distinct precursor peptides. The gp96 was associated with the octamer and one of the two precursors. Thus, each of the hsps bound a distinct set of peptides. Our results have demonstrated for the first time that the hsps associate not only with final sized tumor Ag peptide but also with its precursors. The implication of this evidence is also discussed in terms of the roles of hsps in MHC class I Ag processing/presentation. PMID- 9973384 TI - Comparison of lung dendritic cells and B cells in stimulating naive antigen specific T cells. AB - Dendritic cells (DCs) are specialized APCs that are important in priming naive T cells and can be manipulated in vitro and in vivo to enhance immunizations against microorganisms and tumors. A limitation in the development of suitable immunotherapeutic vaccines for the lung is incomplete information on the role of DCs and other potential APCs in the lung in priming naive T cells. In the current study, we analyzed the relative contributions of murine lung DCs and B cells to process and present OVA to naive CD4+ OVA323-339-specific (DO11.10) T cells in vitro. We also examined their expression of MHC class II and accessory molecules before and after maturation in culture. Similar to DCs from other sites, freshly isolated lung DCs can process OVA, spontaneously up-regulate MHC class II and accessory molecules during overnight culture, and stimulate naive T cells in an Ag-specific manner. In contrast, freshly isolated lung B cells were unable to both process and present native OVA. Furthermore, under conditions of limited OVA323-339 peptide exposure, B cells had a significantly diminished capacity to stimulate T cells, and this correlated with a decreased density of both MHC class II and important costimulatory molecules as compared with lung DCs. PMID- 9973385 TI - Specificity of the SH2 domains of SHP-1 in the interaction with the immunoreceptor tyrosine-based inhibitory motif-bearing receptor gp49B. AB - Inhibitory receptors on hemopoietic cells critically regulate cellular function. Despite their expression on a variety of cell types, these inhibitory receptors signal through a common mechanism involving tyrosine phosphorylation of the immunoreceptor tyrosine-based inhibitory motif (ITIM), which engages Src homology 2 (SH2) domain-containing cytoplasmic tyrosine or inositol phosphatases. In this study, we have investigated the proximal signal-transduction pathway of an ITIM bearing receptor, gp49B, a member of a newly described family of murine NK and mast cell receptors. We demonstrate that the tyrosine residues within the ITIMs are phosphorylated and serve for the association and activation of the cytoplasmic tyrosine phosphatase SHP-1. Furthermore, we demonstrate a physiologic association between gp49B and SHP-1 by coimmunoprecipitation studies from NK cells. To address the mechanism of binding between gp49B and SHP-1, binding studies involving glutathione S-transferase SHP-1 mutants were performed. Utilizing the tandem SH2 domains of SHP-1, we show that either SH2 domain can interact with phosphorylated gp49B. Full-length SHP-1, with an inactivated amino SH2 domain, also retained gp49B binding. However, binding to gp49B was disrupted by inactivation of the carboxyl SH2 domain of full-length SHP-1, suggesting that in the presence of the phosphatase domain, the carboxyl SH2 domain is required for the recruitment of phosphorylated gp49B. Thus, gp49B signaling involves SHP 1, and this association is dependent on tyrosine phosphorylation of the gp49B ITIMs, and an intact SHP-1 carboxyl SH2 domain. PMID- 9973386 TI - Processing of HIV-1 envelope glycoprotein for class I-restricted recognition: dependence on TAP1/2 and mechanisms for cytosolic localization. AB - Processing of viral proteins for recognition by CTL involves degradation of the proteins in the cytosol of an infected cell followed by transport of the resulting peptides into the endoplasmic reticulum (ER) by the TAP1/2 complex. Uncertainty exists over the site of processing of viral envelope (env) proteins since the extracellular domains of env proteins are not present in the cytosol where the class I Ag-processing pathway begins. Rather, the ectodomains of env proteins are cotranslationally translocated into the ER during biosynthesis. To analyze env protein processing, we used the herpes simplex virus protein ICP47 to block peptide transport by TAP1/2 and examined the effects of TAP blockade on the processing of the HIV-1 env protein. For the majority of env-specific CD8+ CTL, the processing pathway required TAP1/2-mediated transport of cytosolic peptides into the ER. To determine how env peptides are generated in the cytosol, we analyzed the processing of two TAP1/2-dependent epitopes containing N-linked glycosylation sites. In each case, processing involved glycosylation-dependent posttranslational modification of asparagine residues to aspartic acid. These results are consistent with cotranslational translocation of env into the ER, where glycosylation occurs. This is followed by export of a fraction of the newly synthesized protein into the cytosol, where it is deglycosylated, with conversion of the asparagines to aspartic acid residues. Following cytoplasmic proteolysis, env peptides are retransported by TAP1/2 into the ER, where association with class I occurs. Thus, the env protein can enter the class I pathway through multiple distinct processing mechanisms. PMID- 9973387 TI - Lymphotoxin alphabeta is expressed on recently activated naive and Th1-like CD4 cells but is down-regulated by IL-4 during Th2 differentiation. AB - Lymphotoxin (LT) is a cytokine that orchestrates lymphoid neogenesis and formation of germinal center reactions. LT exists as a membrane heterotrimer of alpha and beta subunits and is secreted as a homotrimer, LTalpha3. Using LTbetaR.Fc, expression of LTalphabeta on CD4 T cell subsets was investigated in a TCR transgenic model. LTalphabeta was evident 24-72 h after activation of naive T cells with specific Ag, and declined thereafter. Early expression was independent of IFN-gamma and IL-12, however, IL-12 prolonged expression. LTalphabeta was reinduced within 2-4 h after Ag restimulation, but declined by 24 h regardless of IL-12 or IFN-gamma priming. Exposure of naive T cells to IL-4 did not affect early LTalphabeta expression at 24 h, but resulted in subsequent down-regulation. IL-4-differentiated Th2 effectors did not re-express LTalphabeta, and LTalphabeta was transiently found on Th1 clones but not Th2 clones. LTalpha3 and TNF were immunoprecipitated from supernatants and lysates of IL-12 primed cells but not IL 4 primed cells. These studies demonstrate that LTalphabeta is expressed by activated naive CD4 cells, unpolarized IL-2-secreting effectors, and Th1 effectors. In contrast, loss of surface LTalphabeta and a lack of LTalpha3 and TNF secretion is associated with prior exposure to IL-4 and a Th2 phenotype. PMID- 9973388 TI - Tpm1, a locus controlling IL-12 responsiveness, acts by a cell-autonomous mechanism. AB - Th phenotype development is controlled not only by cytokines but also by other parameters including genetic background. One site of genetic variation between murine strains that has direct impact on Th development is the expression of the IL-12 receptor. T cells from B10.D2 and BALB/c mice show distinct control of IL 12 receptor expression. When activated by Ag, B10.D2 T cells express functional IL-12 receptors and maintain IL-12 responsiveness. In contrast, under the same conditions, BALB/c T cells fail to express IL-12 receptors and become unresponsive to IL-12, precluding any Th1-inducing effects if subsequently exposed to IL-12. Previously, we identified a locus, which we termed T cell phenotype modifier 1 (Tpm1), on murine chromosome 11 that controls this differential maintenance of IL-12 responsiveness. In this study, we have produced a higher resolution map around Tpm1. We produced and analyzed a series of recombinants from a first-generation backcross that significantly narrows the genetic boundaries of Tpm1. This allowed us to exclude from consideration certain previous candidates for Tpm1, including IFN-regulatory factor-1. Also, cellular analysis of F1(B10.D2 x BALB/c) T cells demonstrates that Tpm1 exerts its effect on IL-12 receptor expression in a cell-autonomous manner, rather than through influencing the extracellular milieu. This result strongly implies that despite the proximity of our locus to the IL-13/IL-4 gene cluster, these cytokines are not candidates for Tpm1. PMID- 9973389 TI - Alterations in CD4-binding regions of the MHC class II molecule I-Ek do not impede CD4+ T cell development. AB - The T cell coreceptors CD4 and CD8 enhance T cell responses to TCR signals by participating in complexes containing TCR, coreceptor, and MHC molecules. These ternary complexes are also hypothesized to play a seminal role during T cell development, although the precise timing, frequency, and consequences of TCR coreceptor-MHC interactions during positive selection and lineage commitment remain unclear. To address these issues, we designed transgenic mice expressing mutant I-Ek molecules with reduced CD4-binding capability. These transgenic lines were crossed to three different lines of I-Ek-specific TCR transgenic mice, and the efficiency of production of CD4+ lineage cells in the doubly transgenic progeny was assessed. Surprisingly, replacing wild-type I-Ek molecules with these mutant molecules did not affect the production of CD4+CD8- thymocytes or CD4+ peripheral T cells expressing any of the three TCRs examined. These data, when considered together with other experiments addressing the role of coreceptor during development, suggest that not all MHC class II-specific thymocytes require optimal and simultaneous TCR-CD4-MHC interactions to mature. Alternatively, it is possible that these particular alterations of I-Ek do not disrupt the CD4-MHC interaction adequately, potentially indicating functional differences between I-A and I-E MHC class II molecules. PMID- 9973390 TI - Evidence for immune regulation in the induction of transplantation tolerance: a conditional but limited role for IL-4. AB - Most experimental models of allograft tolerance depend on manipulation of immune responses at the time of transplant. In such systems, the graft itself probably plays an important role in the induction of unresponsiveness but as a consequence may suffer immune mediated damage. Ideally, recipients would be made specifically unresponsive before transplant such that the graft is protected from the outset. In this report, we demonstrate that CBA mice pretreated with donor-specific transfusion plus anti-CD4 Ab 28 days before transplant accept cardiac allografts indefinitely without further intervention. Adoptive transfer of spleen cells from mice with long term surviving grafts results in donor-specific graft acceptance in naive secondary recipients, indicating that tolerance in this system involves immuneregulation. Regulation develops as a result of the pretreatment protocol alone, since transfer of cells from pretreated but untransplanted mice to naive recipients also leads to prolonged allograft survival without additional therapy. Neutralizing IL-4 at the time of tolerance induction had no effect on graft outcome in primary recipients. However, removal of IL-4 from the adoptive transfer donors at the time of tolerance induction prevented long term engraftment in the majority of secondary recipients. Our data demonstrate that pretreatment of transplant recipients can establish immune regulation powerful enough to override the responses of an intact immune repertoire and that under stringent conditions at least, development of this regulatory population may in part be dependent on IL-4. PMID- 9973391 TI - TCR, LFA-1, and CD28 play unique and complementary roles in signaling T cell cytoskeletal reorganization. AB - T cells interacting with APCs undergo rearrangement of surface receptors and cytoskeletal elements to face the zone of contact with the APC. This polarization process is thought to affect T cell signaling by organizing a specialized domain on the T cell surface and to direct T cell effector function toward the appropriate APC. We have investigated the contribution of TCR, CD28, and LFA-1 signaling to T cell cytoskeletal polarization by assaying the response of an Ag specific Th1 clone toward a panel of transfected APCs expressing MHC class II alone or in combination with ICAM-1 or B7-1. We show that polarization of talin, an actin-binding protein, occurs in response to integrin engagement. In contrast, reorientation of the T cell microtubule-organizing center (MTOC) is dependent on and directed toward the site of TCR signaling, regardless of whether integrins or costimulatory molecules are engaged. MTOC reorientation in response to peptide MHC complexes is sensitive to the phosphatidylinositol 3-kinase inhibitor wortmannin. CD28 coengagement overcomes this sensitivity, as does activation via Ab cross-linking of the TCR or via covalent peptide-MHC complexes, suggesting that phosphatidylinositol 3-kinase is not required per se but rather plays a role in signal amplification. Engagement of TCR in trans with LFA-1 results in separation of MTOC reorientation and cortical cytoskeletal polarization events, indicating that the two processes are not directly mechanistically linked. These studies show that T cells mobilize individual cytoskeletal components in response to distinct and specific cell surface interactions. PMID- 9973392 TI - Monocytes stimulate expression of the Bcl-2 family member, A1, in endothelial cells and confer protection against apoptosis. AB - We have investigated the molecular mechanisms underlying the ability of peripheral blood monocytes to block apoptosis induction in endothelial cells. Monocytes stimulated the expression of the bcl-2 homologue A1 in serum-starved endothelial cells after 6 h of coincubation, with elevated A1 levels persisting for up to 21 h. IL-1 and TNF also stimulated A1 expression at 6 h, but A1 transcript levels fell by 21 h. Direct cellular contact with monocytes was required for stimulation of A1 mRNA in endothelial cells. Stimulation of endothelial cell A1 mRNA by monocytes was not inhibited by anti-beta2 integrin Abs, but anti-platelet endothelial cell adhesion molecule-1 (PECAM-1) mAb reduced A1 transcript levels at 21 h. Studies employing either TNF on its own, or anti TNF in endothelium/monocyte cocultures showed that TNF plays a role in the early (6-h) stimulation of A1, but is less important for the sustained elevation of A1 levels at 21 h. Serum-starved endothelial cells demonstrated increased survival and decreased apoptosis after coculture with monocytes. IL-10 reduced A1 mRNA expression in, as well as survival of, endothelial cells that were cocultured with monocytes. In comparison with A1, Bcl-2 was expressed at low levels and was up-regulated by monocytes only at 21 h, while neither Bax nor Bcl-xL levels were altered by monocytes. The interaction of monocytes with endothelium during the course of an inflammatory reaction may provide survival signals to endothelial cells. PMID- 9973393 TI - CD40-CD154 interaction and IFN-gamma are required for IL-12 but not prostaglandin E2 secretion by microglia during antigen presentation to Th1 cells. AB - IL-12 and PGE2 promote and inhibit, respectively, the development of Th1 responses. Production of these mediators by APC residing in the central nervous system (CNS) may be involved in the local regulation of the T cell phenotype during infectious and autoimmune CNS diseases. In the present study we have examined IL-12 and PGE2 secretion by cultured microglia and astrocytes from the mouse brain upon Ag-dependent interaction with I-Ad-restricted, OVA323-339 specific TCR transgenic Th1 and Th2 cell lines. We show that microglia, which restimulate efficiently both Th1 and Th2 cells, secrete IL-12 upon Ag-dependent interaction with Th1, but not with Th2 cells. Th1-driven IL-12 production depends on TCR ligation by MHC class II/peptide complexes, CD40 engagement on microglia, and IFN-gamma secretion by activated Th1 cells. Th1 and, to a lesser extent, Th2 cells also stimulate the production of PGE2 by microglia. T cell-mediated induction of PGE2 requires MHC class II/peptide/TCR interactions but does not depend on CD40 engagement or on the presence of IFN-gamma. Astrocytes, which preferentially activate Th2 cells, fail to produce IL-12 and secrete negligible amounts of PGE2 upon interaction with either Th1 or Th2 cells. These results suggest that during CNS infection or immunopathology, IL-12 produced by microglia upon Ag-specific interaction with Th1 cells may further skew the immune response to Th1, whereas the T cell-dependent production of PGE2 by microglia may represent a negative feedback mechanism, limiting the propagation of Th1 responses. PMID- 9973394 TI - cAMP up-regulates cell surface expression of lymphocyte CXCR4: implications for chemotaxis and HIV-1 infection. AB - The chemokine receptor CXCR4 mediates lymphocyte chemotaxis in response to stromal cell-derived factor-1 (SDF-1) and functions as a coreceptor for T cell tropic strains of HIV-1. We examined the role of the cAMP-protein kinase A (PKA) signaling pathway in regulating expression of CXCR4. In response to exogenous dibutyryl cAMP or cAMP-inducing ligands, cell surface expression of CXCR4 was increased by up to 10-fold on CD3/CD28-stimulated PBMC and by up to sixfold on unstimulated PBMC. cAMP did not alter receptor mRNA levels or affect the size of the total CXCR4 pool. However, cAMP did significantly reduce CXCR4 internalization rates and thereby increased the fraction of the total CXCR4 pool expressed on the cell surface. cAMP-induced increases in CXCR4 expression counteracted SDF-1-induced receptor internalization and enhanced both chemotactic response to SDF-1 and cellular vulnerability to HIV-1 infection. Thus, altered chemokine receptor expression may provide one mechanism by which cAMP-inducing ligands influence lymphocyte localization and HIV pathogenesis. PMID- 9973395 TI - Endotoxin down-regulates T cell activation by antigen-presenting liver sinusoidal endothelial cells. AB - Endotoxin is physiologically present in portal venous blood at concentrations of 100 pg/ml to 1 ng/ml. Clearance of endotoxin from portal blood occurs through sinusoidal lining cells, i.e., Kupffer cells, and liver sinusoidal endothelial cells (LSEC). We have recently shown that LSEC are fully efficient APCs. Here, we studied the influence of endotoxin on the accessory function of LSEC. Incubation of Ag-presenting LSEC with physiological concentrations of endotoxin lead to >/=80% reduction of the accessory function, measured by release of IFN-gamma from CD4+ T cells. In contrast, conventional APC populations rather showed an increase of the accessory function after endotoxin treatment. Inhibition of the accessory function in LSEC by endotoxin was not due to lack of soluble costimulatory signals, because neither supplemental IL-1beta, IL-2, IFN-gamma, or IL-12 could rescue the accessory function. Ag uptake was not influenced by endotoxin in LSEC. However, we found that endotoxin led to alkalinization of the endosomal/lysomal compartment specifically in LSEC but not in bone marrow macrophages, which indicated that Ag processing, i.e., proteolytic cleavage of protein Ags into peptide fragments, was affected by endotoxin. Furthermore, endotoxin treatment down-regulated surface expression of constitutively expressed MHC class II, CD80, and CD86. In conclusion, it is conceivable that endotoxin does not alter the clearance function of LSEC to remove gut-derived Ags from portal blood but specifically affects Ag processing and expression of the accessory molecules in these cells. Consequently, Ag-specific immune responses by CD4+ T cells are efficiently down-regulated in the hepatic microenvironment. PMID- 9973396 TI - Protein interactions of Src homology 2 (SH2) domain-containing inositol phosphatase (SHIP): association with Shc displaces SHIP from FcgammaRIIb in B cells. AB - Our recent studies revealed that the inositol phosphatase Src homology 2 (SH2) domain-containing inositol phosphatase (SHIP) is phosphorylated and associated with Shc exclusively under negative signaling conditions in B cells, which is due to recruitment of the SHIP SH2 domain to the FcgammaRIIb. In addition, we reported that SHIP-Shc interaction involves both SHIP SH2 and Shc phosphotyrosine binding domains. These findings reveal a paradox in which the single SH2 domain of SHIP is simultaneously engaged to two different proteins: Shc and FcgammaRIIb. To resolve this paradox, we examined the protein interactions of SHIP. Our results demonstrated that isolated FcgammaRIIb contains SHIP but not Shc; likewise, Shc isolates contain SHIP but not FcgammaRIIb. In contrast, SHIP isolates contain both proteins, revealing two separate pools of SHIP: one bound to FcgammaRIIb and one bound to Shc. Kinetic studies reveal rapid SHIP association with FcgammaRIIb but slower and more transient association with Shc. Affinity measurements using a recombinant SHIP SH2 domain and phosphopeptides derived from FcgammaRIIb (corresponding to Y273) and Shc (corresponding to Y317) revealed an approximately equal rate of binding but a 10-fold faster dissociation rate for FcgammaRIIb compared with Shc phosphopeptide and yielding in an affinity of 2.1 microM for FcgammaRIIb and 0.26 microM for Shc. These findings are consistent with a model in which SHIP transiently associates with FcgammaRIIb to promote SHIP phosphorylation, whereupon SHIP binds to Shc and dissociates from FcgammaRIIb. PMID- 9973397 TI - T cell epitopes of a lipocalin allergen colocalize with the conserved regions of the molecule. AB - In this study we characterized the human T cell-reactive sites of the major cow dander allergen, Bos d 2, a member of the lipocalin protein family. We showed that Bos d 2 contains only a limited number of epitopes. This is in contrast to many other allergens, which usually contain multiple T cell epitopes throughout the molecule. The epitopes of Bos d 2 were primarily concentrated in the conserved regions of the molecule. One of the epitopes was recognized by all the cow-asthmatic individuals regardless of their HLA phenotype. Computer-predicted T cell epitopes on Bos d 2, other lipocalin allergens, and human endogenous lipocalins were situated in similar locations on these molecules and corresponded to experimentally identified epitopes on Bos d 2. The results suggest that human endogenous lipocalins could be involved in the modulation of immune responses against exogenous lipocalin allergens. In addition, our findings are likely to facilitate the development of new forms of immunotherapy against allergies induced by the important group of lipocalin allergens. PMID- 9973398 TI - Induction of specific T cell tolerance by Fas ligand-expressing antigen presenting cells. AB - Autocrine interaction of Fas and Fas ligand leads to apoptosis of activated T cells, a process that is critical for the maintenance of peripheral T cell tolerance. Paracrine interactions of Fas ligand with T cells also may play an important role in the maintenance of tolerance, as Fas ligand can create immune privileged sites and prevent graft rejection by inducing apoptosis in T cells. We surmised that APCs that express Fas ligand might directly induce apoptosis of T cells during presentation of Ag to the T cells, thus inducing Ag-specific, systemic T cell tolerance. Here, we show that profound, specific T cell unresponsiveness to alloantigen was induced by treatment of H-2k mice with H-2b APCs that expressed Fas ligand and that profound T cell unresponsiveness specific for the H-Y Ag was induced by treatment of H-2Db/H-Y TCR transgenic female mice with H-2Db/H-Y APCs that expressed Fas ligand. The induction of this systemic T cell tolerance required the expression of Fas ligand on the APCs as well as the expression of Fas on the T cells. The tolerance was restricted to the Ag presented by the APCs. The rapid and profound clonal deletion of the Ag-specific, peripheral T cells mediated by the Fas ligand-expressing APCs contributed to the induction of tolerance. These findings demonstrate that Ag-specific T cell tolerance can be induced by APCs that express Fas ligand and suggest a novel function for APCs in the induction of T cell apoptosis. Furthermore, they indicate a novel immunointervention strategy for treatment of graft rejection and autoantigen-specific autoimmune diseases. PMID- 9973399 TI - Profound enhancement of T cell activation mediated by the interaction between the TCR and the D3 domain of CD4. AB - CD4 plays an important role in the activation and development of CD4+ T cells. This is mediated via its bivalent interaction with MHC class II molecules and the TCR:CD3 complex through p56lck. Recent studies have implicated a third site of interaction between the membrane-proximal extracellular domains of CD4 and the TCR. Due to these multiple interactions, direct evidence for the functional importance of this extracellular association has remained elusive. Furthermore, the residues that mediate this interaction are unknown. In this study, we analyzed the function of 61 CD4 mutants. Alanine substitution of just 2 residues, either Q114/F182 or F182/F201, which are partially buried and located close to the D2/D3 interface, completely abrogated CD4 function. Direct evidence for the functional importance of TCR:CD4.D3 interaction was obtained using an anti CD3fos:anti-CD4jun-bispecific Ab. Surprisingly, it induced strong T cell activation in hybridomas transfected with cytoplasmic-tailless CD4, despite the lack of association with either p56lck or MHC class II molecules. However, this effect was completely abrogated with the CD4 mutants Q114A/F182A or F182A/F201A. These data demonstrate that TCR:CD4.D3 interaction can have a profound effect on T cell activation and obviates the need for receptor oligomerization. PMID- 9973400 TI - TNF receptor p55 plays a pivotal role in murine keratinocyte apoptosis induced by ultraviolet B irradiation. AB - Excess exposure of skin to ultraviolet B (UVB) results in the appearance of so called sunburn cells. Although it has been demonstrated that sunburn cells represent apoptotic keratinocytes, the molecular mechanisms for UVB-induced apoptosis in keratinocytes have not been fully elucidated. The cytokine, TNF alpha, has been shown to induce apoptosis in a variety of cell types. Since UVB induces keratinocytes to release TNF-alpha, we hypothesized that TNF-alpha is involved in UVB-induced apoptosis in keratinocytes. In order to confirm this hypothesis and to further delineate which type of TNF receptor signaling mediates the apoptosis pathway, we performed both in vivo and in vitro experiments using gene-targeted knockout mice lacking either the TNF p55 receptor or the TNF p75 receptor. In the in vivo study, wild-type and mutant mice were exposed to UVB, and apoptotic keratinocytes were detected by examining DNA fragmentation using in situ nick-end labeling. For the in vitro experiments, keratinocytes derived from the wild-type and mutant mice were irradiated with UVB, and the degree of apoptosis was determined by flow cytometry, nick-end labeling of DNA, and a DNA ladder assay. Both in vivo and in vitro studies demonstrated that the deletion of TNF receptor p55 could suppress UVB-induced apoptosis in keratinocytes. Our observations support the notion that TNF-alpha is involved in UVB-induced keratinocyte apoptosis, and demonstrate that p55 receptor signaling plays a pivotal role in this event. PMID- 9973401 TI - Distinct effects of Jak3 signaling on alphabeta and gammadelta thymocyte development. AB - Janus kinase 3 (Jak3) plays a central role in the transduction of signals mediated by the IL-2 family of cytokine receptors. Targeted deletion of the murine Jak3 gene results in severe reduction of alphabeta and complete elimination of gammadelta lineage thymocytes and NK cells. The developmental blockade appears to be imposed on early thymocyte differentiation and/or expansion. In this study, we show that bcl-2 expression and in vivo survival of immature thymocytes are greatly compromised in Jak3-/- mice. There is no gross deficiency in rearrangements of the TCRdelta and certain gamma loci in pre-T cells, and a functional gammadelta TCR transgene cannot rescue gammadelta lineage differentiation in Jak3-/- mice. In contrast, a TCRbeta transgene is partially able to restore alphabeta thymocyte development. These data suggest that the signals mediated by Jak3 are critical for survival of all thymocyte precursors particularly during TCRbeta-chain gene rearrangement, and are continuously required in the gammadelta lineage. The results also emphasize the fundamentally different requirements for differentiation of the alphabeta and gammadelta T cell lineages. PMID- 9973402 TI - Evidence for repression of IL-2 gene activation in anergic T cells. AB - The induction of clonal anergy in a T cell inhibits IL-2 secretion because of the development of a proximal signal transduction defect. Fusion of anergic murine T cells to human Jurkat T leukemia cells and formation of heterokaryons failed to result in a complementation of this signaling defect and restoration of murine IL 2 mRNA inducibility. Instead, signal transduction to the human IL-2 gene became disrupted. Heterokaryons formed by the fusion of anergic murine T cells to normal murine T cells also failed to accumulate intracellular IL-2 protein in response to stimulation either with the combination of CD3 and CD28 mAbs or with ionomycin plus a protein kinase C-activating phorbol ester. The results argue against a loss-of-function signaling defect as the sole basis for clonal anergy induction and document the presence of a dominant-acting repressor molecule that inhibits signal transduction to the IL-2 gene within viable anergic T cells. PMID- 9973403 TI - Elevation of mitochondrial transmembrane potential and reactive oxygen intermediate levels are early events and occur independently from activation of caspases in Fas signaling. AB - Stimulation of the CD95/Fas/Apo-1 receptor leads to apoptosis through activation of the caspase family of cysteine proteases and disruption of the mitochondrial transmembrane potential (Deltapsim). We show that, in Jurkat human T cells and peripheral blood lymphocytes, Fas-induced apoptosis is preceded by 1) an increase in reactive oxygen intermediates (ROI) and 2) an elevation of Deltapsim. These events are followed by externalization of phosphatidylserine (PS), disruption of Deltapsim, and cell death. The caspase inhibitor peptides, DEVD-CHO, Z-VAD.fmk, and Boc-Asp.fmk, blocked Fas-induced PS externalization, disruption of Deltapsim, and cell death, suggesting that these events are sequelae of caspase activation. By contrast, in the presence of caspase inhibitors, ROI levels and Deltapsim of Fas-stimulated cells remained elevated. Because ROI levels and Deltapsim are regulated by the supply of reducing equivalents from the pentose phosphate pathway (PPP), we studied the impact of transaldolase (TAL), a key enzyme of the PPP, on Fas signaling. Overexpression of TAL accelerated Fas-induced mitochondrial ROI production, Deltapsim elevation, activation of caspase-8 and caspase-3, proteolysis of poly(A)DP-ribose polymerase, and PS externalization. Additionally, suppression of TAL diminished these activities. Therefore, by controlling the balance between mitochondrial ROI production and metabolic supply of reducing equivalents through the PPP, TAL regulates susceptibility to Fas induced apoptosis. Early increases in ROI levels and Deltapsim as well as the dominant effect of TAL expression on activation of caspase-8/Fas-associated death domain-like IL-1beta-converting enzyme, the most upstream member of the caspase cascade, suggest a pivotal role for redox signaling at the initiation of Fas mediated apoptosis. PMID- 9973404 TI - Activation of the signal transducer glycoprotein 130 by both IL-6 and IL-11 requires two distinct binding epitopes. AB - The coordination and regulation of immune responses are primarily mediated by cytokines that bind to specific cell surface receptors. Glycoprotein 130 (gp130) belongs to the family of class I cytokine receptors and is the common signal transducing receptor subunit shared by the so-called IL-6 type cytokines (IL-6, IL-11, ciliary neurotrophic factor, leukemia inhibitory factor, oncostatin M, and cardiotrophin-1). The inflammatory cytokines IL-6 and IL-11 induce gp130 homodimerization after binding to their specific alpha receptors, which leads to the activation of the Janus kinase/STAT signal transduction pathway. A molecular model of IL-6/IL-6R/gp130, which is based on the structure of the growth hormone/growth hormone receptor complex, allowed the selection of several amino acids located in the cytokine-binding module of gp130 for mutagenesis. The mutants were analyzed with regard to IL-6- or IL-11-induced STAT activation and ligand binding. It was found that Y190 and F191 are essential for the interaction of gp130 with IL-6 as well as IL-11, suggesting a common mode of recognition of helical cytokines by class I cytokine receptors. Furthermore, the requirement of the gp130 N-terminal Ig-like domain for ligand binding and signal transduction was demonstrated by the use of deletion mutants. Thus, besides the observed analogy to the growth hormone/growth hormone receptor complex, there is a substantial difference in the mechanism of receptor engagement by cytokines that signal via gp130. PMID- 9973405 TI - A critical tyrosine residue in the cytoplasmic tail is important for CD1d internalization but not for its basolateral sorting in MDCK cells. AB - The CD1 family of polypeptides is divided into two groups, the CD1b and CD1d group. Both groups are involved in stimulation of T cell response. Molecules of the CD1b group can present Ag derived from bacterial cell walls to T cells; the process of Ag acquisition is thought to take place in endosomes. Little is known about Ag presentation by CD1d. We therefore studied the intracellular trafficking of human CD1d in Madin-Darby canine kidney (MDCK) and COS cells. CD1d was found in endosomal compartments after its internalization from the plasma membrane. It is therefore possible that CD1d acquires its yet unidentified exogenous ligand in the same compartments as the MHC class II and CD1b molecules. CD1d contains a tyrosine-based sorting signal in its cytoplasmic tail that is necessary for internalization. Furthermore, the cytoplasmic tail of CD1d also contains a signal for basolateral sorting that is, however, different from the internalization signal. PMID- 9973406 TI - The mapping of the Lyn kinase binding site of the common beta subunit of IL 3/granulocyte-macrophage colony-stimulating factor/IL-5 receptor. AB - It has been shown that a membrane-proximal region within common beta (betac) receptor of IL-3/granulocyte-macrophage CSF/IL-5 (amino acids 450-517) is important for Lyn binding. We have shown previously that Lyn kinase is physically associated with the IL-5R betac subunit in unstimulated cells. The result suggests that this association involves binding modules that are not activation or phosphorylation dependent. The objective of this study was to map the exact Lyn binding site on betac. Using overlapping and/or sequential peptides derived from betac 450-517, we narrowed down the Lyn binding site to nine amino acid residues, betac 457-465. The P-->A mutation in this region abrogated the binding to Lyn, indicating a critical role of proline residues. We created a cell permeable Lyn-binding peptide by N-stearation. This cell-permeable peptide blocked the association of Lyn, but not Jak2 with betac in situ. We also investigated the betac binding site of Lyn kinase. Our results suggest that the N terminal unique domain of Lyn kinase is important for binding to betac receptor. To our knowledge, this is the first molecular identification of the Lyn binding site of betac receptor. This finding may help develop specific inhibitors of Lyn coupled signaling pathways. PMID- 9973407 TI - Class II-associated invariant chain peptide-independent binding of invariant chain to class II MHC molecules. AB - The class II-associated invariant chain peptide (CLIP) region of invariant chain (Ii) is believed to play a critical role in the assembly and transport of MHC class II alphabetaIi complexes through its interaction with the class II peptide binding site. The role of the CLIP sequence was investigated by using mutant Ii molecules with altered affinity for the DR1 peptide-binding site. Both high- and low-affinity mutants were observed to efficiently assemble with DR1 and mediate transport to endosomal compartments in COS cell transfectants. Using N- and C terminal truncations, a region adjacent to CLIP within Ii(103-118) was identified that can complement loss of affinity for the peptide-binding site in mediating efficient assembly of alphabetaIi. A C-terminal fragment completely lacking the CLIP region, Ii(103-216), was observed binding stably to class II molecules in immunoprecipitation studies and experiments with purified proteins. The Ii(103 118) region was required for this binding, which occurs through interactions outside of the alphabeta peptide-binding groove. We conclude that strong interactions involving Ii(103-118) and other regions of Ii cooperate in the assembly of functional alphabetaIi under conditions where CLIP has little or no affinity for the class II peptide-binding site. Our results support the hypothesis that the CLIP sequence has evolved to avoid high-stability interactions with the peptide-binding sites of MHC class II molecules rather than as a promiscuous binder with moderate affinity for all class II molecules. PMID- 9973408 TI - Lipopolysaccharide inhibits TNF-induced apoptosis: role of nuclear factor-kappaB activation and reactive oxygen intermediates. AB - LPS, a component of the cell wall in Gram-negative bacteria, induces inflammation and septic shock syndrome by stimulating various inflammatory cytokines including TNF. How LPS affects the TNF-mediated cellular responses, however, is not understood. In this study, the effect of LPS on TNF-mediated apoptosis in human histiocytic lymphoma U-937 cells was investigated. We found that treatment of cells with LPS completely abolished TNF-mediated cytotoxicity and activation of caspase-3. LPS-chelating antibiotic, polymyxin B, suppressed the antiapoptotic activity, indicating the specificity of the effect. Within minutes, LPS through CD14 induced the activation of NF-kappaB, degradation of IkappaBalpha (inhibitory subunit of NF-kappaB) and IkappaBbeta, and nuclear translocation of p65. An antioxidant, pyrrolidine dithiocarbamate, which blocked LPS-induced NF-kappaB activation, also abolished the antiapoptotic effects of LPS at the same time. Besides TNF, the apoptosis induced by taxol and okadaic acid was also sensitive to LPS-induced NF-kappaB activation, whereas that induced by H2O2, doxorubicin, daunomycin, vincristine, and vinblastine was NF-kappaB insensitive. Tumor cells that constitutively expressed NF-kappaB also showed resistance to the apoptotic effects of TNF, taxol, and okadaic acid, but sensitivity to all other agents, indicating the critical role of NF-kappaB in blocking apoptosis induced by certain agents. Overall, these results indicate that LPS induces resistance to the apoptotic effects of TNF and other agents, and that NF-kappaB activation, whether induced or constitutive, inhibits this apoptosis. PMID- 9973409 TI - Structure and genomic organization of a second cluster of immunoglobulin heavy chain gene segments in the channel catfish. AB - The structure, organization, and partial sequence of a 25-kb genomic region containing a second cluster of H chain gene segments in the channel catfish (Ictalurus punctatus) has been determined. Multiple VH gene segments, representing different VH families, are located upstream of a germline-joined VDJ. The VDJ segment has a split leader sequence and a single open reading consistent with that expressed in members of the VH1 family. Downstream of the germline-joined VDJ is a single JH segment and two pseudogene exons structurally similar to the Cmu1 and Cmu2 exons of the functional gene. Both pseudogene exons are multiply crippled with RNA splice sites destroyed, and open reading frames are interrupted by termination codons, insertions, and/or deletions. Sequence alignment of a 10.8-kb region within the second H chain cluster with the genomic sequence of the nine JH segments and the functional Cmu within the first H chain gene cluster indicates that the second H chain gene cluster probably arose by a massive duplication event. The JH region of the VDJ, the coding and flanking regions of the single JH segment, and the pseudogene Cmu exons were readily aligned with homologous segments in the first gene cluster. This duplication event may have extended to include the upstream VH segments. A member of the Tc1 mariner family of transposable elements is located downstream of the pseudogene Cmu2, which suggests that the transposition may have contributed to the evolution of the duplicated Cmu. PMID- 9973410 TI - Interaction of murine MHC class I molecules with tapasin and TAP enhances peptide loading and involves the heavy chain alpha3 domain. AB - In human cells the association of MHC class I molecules with TAP is thought to be mediated by a third protein termed tapasin. We now show that tapasin is present in murine TAP-class I complexes as well. Furthermore, we demonstrate that a mutant H-2Dd molecule that does not interact with TAP due to a Glu to Lys mutation at residue 222 of the H chain (Dd(E222K)) also fails to bind to tapasin. This finding supports the view that tapasin bridges the association between class I and TAP and implicates residue 222 as a site of contact with tapasin. The inability of Dd(E222K) to interact with tapasin and TAP results in impaired peptide loading within the endoplasmic reticulum. However, significant acquisition of peptides can still be detected as assessed by the decay kinetics of cell surface Dd(E222K) molecules and by the finding that prolonged viral infection accumulates sufficient target structures to stimulate T cells at 50% the level observed with wild-type Dd. Thus, although interaction with tapasin and TAP enhances peptide loading, it is not essential. Finally, a cohort of Dd(E222K) molecules decays more rapidly on the cell surface compared with wild-type Dd molecules but much more slowly than peptide-deficient molecules. This suggests that some of the peptides obtained in the absence of an interaction with tapasin and TAP are suboptimal, suggesting a peptide-editing function for tapasin/TAP in addition to their role in enhancing peptide loading. PMID- 9973411 TI - Germline structure and differential utilization of Igha and Ighb VH10 genes. AB - Ab heavy chains encoded by mouse VH10 genes have been of particular interest due to their frequent association with DNA binding. We reported previously that VH10 sequences are over-represented in the preimmune repertoire considering the apparent number of germline-encoded VH10 gene segments. In this report, we show that the VH10 family consists of three and two germline genes in the Igha and Ighb haplotypes, respectively. The complete nucleotide sequences of these five genes, including promoters and recombination signal sequences, were determined and allow unambiguous assignment of allelic relationships. The usage of individual VH10 genes varied significantly and ranged from 0.2% to an extraordinary 7.2% of the VH genes expressed by splenic B cells. Since the promoter and recombination signal sequence elements of all five VH10 genes are identical, we suggest that the few amino acid differences encoded by these five germline VH10 genes determine their representation in the preimmune repertoire. Rearrangements of the most frequently used VH10 gene have an apparent bias for histidine at position 95 of complementarity-determining region-3 (CDR3). These CDR3s are also biased for asparagine, an amino acid associated with the CDRs of DNA binding Abs. Together, these results suggest that high VH10 gene use is the result of B cell receptor-mediated selection and may involve DNA and/or ligands that share antigenic features with DNA. PMID- 9973412 TI - AIDS primary central nervous system lymphoma: molecular analysis of the expressed VH genes and possible implications for lymphomagenesis. AB - AIDS-associated primary central nervous system lymphomas are late events that have an extremely poor prognosis. Despite different hypotheses, the brain localization of these B cell lymphomas remains an enigma. To better define the cell origin of the lymphomas and the possible role of the B cell receptor (BCR) in the brain localization and/or in the oncogenic transformation, we analyzed the V region genes of the Ig heavy chain expressed by lymphoma cells in five randomly selected patients. After amplifying the rearranged VHDJH DNA by PCR, cloning, and sequencing of the amplified products, we observed that: 1) of the five lymphomas analyzed, four were clearly monoclonal; 2) there was no preferential use of one peculiar VH family or one peculiar segment of gene; 3) the mutation analysis showed that an Ag-driven process occurred in at least two cases, probably before the oncogenic event; and 4) there was no intraclonal variability, suggesting that the hypermutation mechanism is no longer efficient in these lymphoma B cells. Taken together, our results suggest that distinct Ags could be recognized by the BCR of the lymphoma cells in different patients and that, if the Ags are responsible for the brain localization of these B cells bearing mutated BCR, other factors must be involved in B cell transformations in primary central nervous system lymphoma. PMID- 9973413 TI - TFEC is a macrophage-restricted member of the microphthalmia-TFE subfamily of basic helix-loop-helix leucine zipper transcription factors. AB - The murine homologue of the TFEC was cloned as part of an analysis of the expression of the microphthalmia-TFE (MiT) subfamily of transcription factors in macrophages. TFEC, which most likely acts as a transcriptional repressor in heterodimers with other MiT family members, was identified in cells of the mononuclear phagocyte lineage, coexpressed with all other known MiT subfamily members (Mitf, TFE3, TFEB). Northern blot analysis of several different cell lineages indicated that the expression of murine TFEC (mTFEC) was restricted to macrophages. A 600-bp fragment of the TATA-less putative proximal promoter of TFEC shares features with many known macrophage-specific promoters and preferentially directs luciferase expression in the RAW264.7 macrophage cell line in transient transfection assays. Five of six putative Ets motifs identified in the TFEC promoter bind the macrophage-restricted transcription factor PU.1 under in vitro conditions and in transfected 3T3 fibroblasts; the minimal luciferase activity of the TFEC promoter could be induced by coexpression of PU.1 or the related transcription factor Ets-2. The functional importance of the tissue restricted expression of TFEC and a possible role in macrophage-specific gene regulation require further investigation, but are likely to be linked to the role of the other MiT family members in this lineage. PMID- 9973414 TI - Atypical VH-D-JH rearrangements in newborn autoimmune MRL mice. AB - Antinuclear Abs are the hallmark of the autoimmune disease systemic lupus erythematosus (SLE). The ability of self reactive autoantibodies to bind to DNA and nucleosomes is partly conferred by an increased number of arginine and asparagine residues in the heavy chain third complementarity determining region. This increased content of cationic residues is primarily the result of unusual VH D-JH rearrangements, which include D-D fusions and D gene inversions. While self Ag-driven clonal expansion is a major contributor to the production of antinuclear Abs in lupus, we explore in this study the hypothesis that newly emerging B cells from autoimmune mice display more frequently these unusual VH-D JH rearrangements. To this end, libraries of PCR-generated VH-D-JH junctions from MRL and C3H newborn livers were analyzed. When compared with the C3H controls, D and JH gene usage in MRL junctions suggests a greater frequency of secondary D-JH rearrangements in this strain. Furthermore, B cells from the autoimmune-prone MRL mice have significantly increased numbers of atypical VH-D-JH rearrangements (D-D fusions and D inversions). Therefore, B cells from MRL mice manifest intrinsic defects that could confer an increased propensity to produce unusual VH-D-JH rearrangements early in ontogeny. PMID- 9973415 TI - MHC class II-dependent NK1.1+ gammadelta T cells are induced in mice by Salmonella infection. AB - We observed the emergence of a novel population of gammadelta T cells expressing NK1.1 Ag in the peritoneal cavity of mice infected with Salmonella choleraesuis. The NK1.1+gammadelta T cells accounted for approximately 20% of all gammadelta T cells emerging in the peritoneal cavity of C57BL/6 mice and expressed preferentially rearranged Vgamma4-Jgamma1 and Vdelta6.3-Ddelta1-Ddelta2-Jdelta1 genes with N diversity. The gammadelta T cells proliferated vigorously in response to PHA-treated spleen cells and produced IFN-gamma in the culture supernatant. However, spleen cells from Abetab-deficient mice were unable to stimulate the gammadelta T cells. Furthermore, the NK1.1+gammadelta T cells were stimulated not only by Chinese hamster ovary (CHO) cells expressing wild-type IAb but also by those expressing IAb/Ealpha52-68 or IAb/pigeon cytochrome c-derived analogue peptide complex. These proliferation activities were inhibited by mAb specific for IAb chain. Consistent with these findings, the emergence of NK1.1+gammadelta T cells was reduced in the peritoneal cavity of Abetab-deficient mice after Salmonella infection, whereas NK1.1+gammadelta T cells were rather abundant in the peritoneal cavity of Salmonella-infected beta2m-deficient mice. Moreover, the NK1.1+gammadelta T cells were easily identified in the thymus of beta2m-deficient but not Abetab-deficient mice. Our results indicated that MHC class II expression is essential for development and activation of NK1. 1+gammadelta T cells in the thymus and the periphery. PMID- 9973416 TI - In vivo IL-12 production and IL-12 receptors beta1 and beta2 mRNA expression in the spleen are differentially up-regulated in resistant B6 and susceptible A/J mice during early blood-stage Plasmodium chabaudi AS malaria. AB - As previously reported, blood-stage Plasmodium chabaudi AS malaria is lethal by days 10-12 postinfection in susceptible A/J mice that mount an early, predominantly Th2 response. In contrast, resistant C57BL/6 (B6) mice clear the infection by 4 wk with an early Th1 response. In this study, we analyzed in vivo production of IL-12, a potent Th1-inducing cytokine, during the first 5 days after P. chabaudi AS infection in these mice. By day 2, serum IL-12 p70 levels were significantly increased in B6 mice over basal levels and were also significantly higher compared with A/J mice that showed no significant changes in serum p70 levels after infection. Splenectomy of resistant B6 mice before infection demonstrated that the spleen is the major source of systemic IL-12 in these hosts. Splenic mRNA levels of both p40 and p35 were significantly higher in A/J mice; however, the ratios of p40/p35 mRNA levels were similarly up-regulated in both strains. Furthermore, B6 but not A/J mice showed significant up regulation of splenic IL-12R beta2 mRNA over basal levels by days 3 and 4, coincident with sustained up-regulation of splenic IFN-gamma mRNA levels on days 3-5. However, IL-12R beta1 mRNA levels in the spleen were similarly up-regulated in both mouse strains by day 3. Taken together, these data suggest that high systemic IL-12 production, accompanied by an early and sustained up-regulation of both IL-12R beta1 and beta2 mRNA levels in the spleen, as occurs in resistant B6 mice, appears to preferentially induce protective Th1 responses against blood stage malaria. PMID- 9973417 TI - Innate immunity in insects: the role of multiple, endogenous serum lectins in the recognition of foreign invaders in the cockroach, Blaberus discoidalis. AB - Unlike vertebrates, insects do not have an Ab-based nonself recognition system, and must rely totally on innate immunity to defend themselves from microbial invaders. The most likely candidates for recognizing foreign material in insects are the lectins, which have already been shown to be important in mammalian innate immunity. The hemolymph of the cockroach, Blaberus discoidalis, contains multiple lectins, designated BDL1, BDL2, BDL3, and GSL (beta-1,3-glucan-specific lectin), two of which, namely BDL1 and GSL, have close similarities to acute phase reactants. These endogenous molecules, as well as Con A, wheat germ agglutinin, and Helix pomatia agglutinin, have been shown to induce an enhanced phagocytic response by B. discoidalis plasmatocytes. This effect is related to the carbohydrates presented on the surface of the microorganism and to the sugar specificities of the lectins. Thus, the mannose-specific lectins, BDL1 and Con A, both increase the phagocytosis of baker's yeast and Escherichia coli, whereas the N-acetyl-D-glucosamine/N-acetyl-D-galactosamine-specific lectins, BDL2, wheat germ agglutinin, and H. pomatia agglutinin, induce the phagocytosis of Bacillus cereus and E. coli. GSL, specific for beta-1,3-glucan, and the N-acetyl-D galactosamine-specific BDL3, only enhance the phagocytosis of yeast and B. cereus, respectively. Phenylthiourea, an inhibitor of the prophenoloxidase system, caused either total, partial, or no inhibition of the lectin-induced increase in phagocytosis, indicating that this immune enhancement results, in some cases, from at least two closely linked mechanisms. These results show that the endogenous lectins in the cockroach hemolymph are capable of acting as nonself recognition molecules for a wide range of microorganisms, and thus obviate the necessity of Abs in these animals. PMID- 9973418 TI - Measles virus infection synergizes with IL-4 in IgE class switching. AB - Increasing evidence suggests that viral infections are associated with the induction and exacerbation of asthma. One characteristic of human asthma is an increase in the levels of circulating IgE. Previous studies have shown that circulating IgE levels are elevated during the early phase of infection with measles virus (MV). We have shown previously that one mechanism by which viral infections can increase IgE levels is via an induction of IgE class switching through the activation of the antiviral protein kinase (dsRNA-activated protein kinase), leading to the activation of multiple NF-kappaB complexes. Therefore, to determine whether infection with MV can also induce IgE class switching, we infected the human Ramos B cell line with the Edmonston strain of MV. Infecting Ramos cells with MV did not result directly in either the activation of dsRNA activated protein kinase or IgE class switching. However, a synergistic effect on IgE class switching was observed when Ramos cells were infected with MV before IL 4 treatment. Ab cross-linking of the MV receptor, CD46, mimicked the effects of MV infection in synergizing with IL-4 to induce IgE class switching, suggesting that viral hemagglutinin is involved in this synergistic effect. These data provide the first indication of a potential mechanism for MV-induced IgE up regulation and suggest a model for a viral-induced exacerbation of IgE-mediated disorders such as asthma. PMID- 9973419 TI - Mucosal DNA vaccine immunization against measles with a highly attenuated Shigella flexneri vector. AB - An intranasal vaccine vector would elicit protective immunity at the respiratory mucosa, the portal of entry and the primary site for replication for measles virus (MV) and other respiratory viruses. In a murine model of pulmonary Shigella, we demonstrate here that a candidate-attenuated Shigella vaccine vector is safely tolerated in IFN-gamma deficient mice at an inoculum that is 1 million fold higher than the inoculum of the wild-type parent strain that would be lethal for greater than 90% of these mice. Also, following intranasal inoculation, the Deltaasd Shigella harboring a DNA MV vaccine plasmid induces a vigorous MV specific Th1-type (both CD8+ CTL and IFN-gamma) and, to a lesser degree, Th2-type responses among splenocytes in addition to low levels of IgG and IgA in the serum. Priming for MV-specific CTL responses was possible in mice that had prior infection with a wild-type Shigella of the same serotype. Remarkably, mice immunized by the intranasal route with attenuated Shigella harboring the DNA MV vaccine plasmid had a level of MV-specific CTL activity among splenocytes that was comparable with levels observed in mice immunized by the i.p. route with attenuated Salmonella typhi harboring the same DNA vaccine plasmid, despite the fact that Shigella remained localized to the lungs, yet Salmonella disseminated to the spleen following inoculation. Thus, Deltaasd Shigella represents a very useful vector for delivery of DNA vaccines to mucosal lymphoid tissues. PMID- 9973420 TI - CpG oligodeoxynucleotides can circumvent the Th2 polarization of neonatal responses to vaccines but may fail to fully redirect Th2 responses established by neonatal priming. AB - Neonatal murine responses to a panel of conventional vaccines differ qualitatively from adult responses by a particular polarization toward a Th2 pattern and a frequent limitation of the Th1 and CTL responses required for protection against intracellular microorganisms. In contrast, DNA vaccines induce adult-like Th1/CTL neonatal responses against the same vaccine Ags. In this report, we show that this can be related to their content in unmethylated CpG motifs. Oligodeoxynucleotides (ODN) containing CpG motifs activate neonatal APCs to produce IL-12 in vitro and induce adult-like Th1 responses to tetanus toxoid and measles Ags in vivo, with production of IgG2a-specific Abs and adult-like secretion of IFN-gamma and IL-5 by Ag-specific T cells. However, in spite of their capacity to trigger neonatal B cell proliferation in vitro, CpG-ODN only partially enhanced early life Ab responses. Finally, using Th1-driving CpG-ODN with the boosting dose of a protein vaccine was sufficient to redirect adult but not neonatally primed Th2 responses. These observations could be important for the development of novel vaccines that will have to be effective early in life. PMID- 9973421 TI - Specific activated T cells regulate IL-12 production by human monocytes stimulated with Cryptococcus neoformans. AB - IL-12 production mediated by a T cell-independent and/or T cell-dependent pathway was investigated in human monocytes responding to Cryptococcus neoformans. The data of this study showed that: 1) appreciable levels of IL-12 were observed when freshly isolated monocytes were exposed to acapsular C. neoformans or Candida albicans and secretion occurred within 24-48 h of incubation; 2) monocytes alone were poor producers of IL-12 when stimulated with encapsulated C. neoformans; 3) the presence of specific anti-glucuronoxylomannan mAb favored IL-12 secretion and Fc cross-linking could play a role; 4) monocytes were able to secrete consistent levels of IL-12 when cultured with activated T cells responding to C. neoformans; 5) the maximum secretion of IL-12 was observed at 5-7 days of culture and was strongly regulated by the presence of endogenous IFN-gamma; and 6) the interaction between CD40 on monocytes and CD40 ligand on activated T lymphocytes responding to C. neoformans played a critical role in IL-12 secretion. These data highlight the mechanisms of IL-12 production by human monocytes exposed to C. neoformans, indicating a possible biphasic secretion of IL-12, dependent on the direct effect of fungal insult, and characterized by consistent secretion of IL 12 that is dependent on the interaction of CD40 with the CD40 ligand expressed on activated T cells responding to C. neoformans. PMID- 9973422 TI - The inflammatory response to nonfatal Sindbis virus infection of the nervous system is more severe in SJL than in BALB/c mice and is associated with low levels of IL-4 mRNA and high levels of IL-10-producing CD4+ T cells. AB - SJL mice are susceptible to inflammatory autoimmune diseases of the central nervous system (CNS), while BALB/c mice are relatively resistant. To understand differences in immune responses that may contribute to autoimmune neurologic disease, we compared the responses of SJL and BALB/c mice to infection with Sindbis virus, a virus that causes acute nonfatal encephalomyelitis in both strains of mice. Clearance of virus was similar, but SJL mice developed a more intense inflammatory response in the brain and spinal cord and inflammation persisted for several weeks. Analysis of lymphocytes isolated from brains early after infection showed an absence of NK cells in SJL mice, while both strains of mice showed CD4+ and CD8+ T cells. During the second week after infection, CD4+ T cells increased in SJL mice and the proportion of CD8+ T cells decreased, while the opposite pattern was seen in BALB/c mice. Expression of IL-10 mRNA was higher and IL-4 mRNA was lower in the brains of infected SJL than in BALB/c mice, while expression of the mRNAs of IL-6, IL-1beta, TNFalpha, and the Th1 cytokines IL-2, IL-12, and IFN-gamma was similar. Lymphocytes isolated from the CNS of SJL mice produced large amounts of IL-10. CNS lymphocytes from both strains of mice produced IFN-gamma in response to stimulation with Sindbis virus, but not in response to myelin basic protein. These data suggest that IL-10-producing CD4+ T cells are differentially recruited to or regulated within the CNS of SJL mice compared with BALB/c mice infected with Sindbis virus, a characteristic that may be related to low levels of IL-4, and is likely to be involved in susceptibility of SJL mice to CNS inflammatory diseases. PMID- 9973423 TI - Role of TNF-alpha in pulmonary host defense in murine invasive aspergillosis. AB - Invasive pulmonary aspergillosis is a common and devastating complication of immunosuppression, whose incidence has increased dramatically in tandem with the increase in the number of immunocompromised patients. Given the role of TNF-alpha in other pulmonary infections, we hypothesized that TNF-alpha is an important proximal signal in murine invasive pulmonary aspergillosis. Intratracheal challenge with Aspergillus fumigatus conidia in both neutropenic (cyclophosphamide-treated) and nonneutropenic BALB/c mice resulted in the time dependent increase in lung TNF-alpha levels, which correlated with the histologic development of a patchy, peribronchial infiltration of mononuclear and polymorphonuclear cells. Ab-mediated neutralization of TNF-alpha resulted in an increase in mortality in both normal and cyclophosphamide-treated animals, which was associated with increased lung fungal burden as determined by histology and as quantified by chitin content. Depletion of TNF-alpha resulted in a reduced lung neutrophil influx in both normal and cyclophosphamide-treated animals, which occurred in association with a decrease in lung levels of the C-X-C chemokine, macrophage inflammatory protein-2 and the C-C chemokines macrophage inflammatory protein-1alpha and JE. In cyclophosphamide-treated animals, intratracheal administration of a TNF-alpha agonist peptide (TNF70-80) 3 days before, but not concomitant with, the administration of Aspergillus conidia resulted in improved survival from 9% in control mice to 55% in TNF70-80-treated animals. These studies indicate that TNF-alpha is a critical component of innate immunity in both immunocompromised and immunocompetent hosts, and that pretreatment with a TNF-alpha agonist peptide in a compartmentalized fashion can significantly enhance resistance to A. fumigatus in neutropenic animals. PMID- 9973424 TI - IFN-gamma is required for viral clearance from central nervous system oligodendroglia. AB - Infection of the central nervous system (CNS) by the JHM strain of mouse hepatitis virus (JHMV) is a rodent model of the human demyelinating disease multiple sclerosis. The inability of effective host immune responses to eliminate virus from the CNS results in a chronic infection associated with ongoing recurrent demyelination. JHMV infects a variety of CNS cell types during the acute phase of infection including ependymal cells, astrocytes, microglia, oligodendroglia, and rarely in neurons. Replication within the majority of CNS cell types is controlled by perforin-dependent virus-specific CTL. However, inhibition of viral replication in oligodendroglia occurs via a perforin independent mechanism(s). The potential role for IFN-gamma as mediator controlling JHMV replication in oligodendroglia was examined in mice deficient in IFN-gamma secretion (IFN-gamma0/0 mice). IFN-gamma0/0 mice exhibited increased clinical symptoms and mortality associated with persistent virus, demonstrating an inability to control replication. Neither antiviral Ab nor CTL responses were diminished in the absence of IFN-gamma, although increased IgG1 was detected in IFN-gamma0/0 mice. Increased virus Ag in the absence of IFN-gamma localized almost exclusively to oligodendroglia and was associated with increased CD8+ T cells localized within white matter. These data suggest that although perforin dependent CTL control virus replication within astrocytes and microglia, which constitute the majority of infected CNS cells, IFN-gamma is critical for control of viral replication in oligodendroglia. Therefore, different mechanisms are used by the host defenses to control virus replication within the CNS, dependent upon the phenotype of the targets of virus replication. PMID- 9973425 TI - Vascular endothelial cell expression of ICAM-1 and VCAM-1 at the onset of eliciting contact hypersensitivity in mice: evidence for a dominant role of TNF alpha. AB - We have studied vascular endothelial activation and increased expression of ICAM 1 and VCAM-1 at the onset of the elicitation phase of oxazolone contact hypersensitivity in mice. By measuring the local uptake of i.v. administered radiolabeled anti-ICAM-1 and anti-VCAM-1 mAb, we found that endothelial ICAM-1 and VCAM-1 was increased by 4 h after challenge, 2 h later than the first peak of ear swelling and 125I-labeled human serum albumen uptake. Increased expression of endothelial ICAM-1 and VCAM-1 was significantly greater in sensitized animals than in naive animals. Anti-TNF-alpha antiserum significantly inhibited both the increase in ear thickness (p < 0.01), and the up-regulation of ICAM-1 and VCAM-1 expression (p < 0.01 for both) at 4 h. In contrast, the combination of anti-IL 1alpha and IL-1beta had only a small inhibitory effect on ICAM-1 expression (p < 0.05) and no significant effect on increased ear thickness or on VCAM-1 expression. A mixture of anti-TNF-alpha, anti-IL-1alpha, and IL-1beta was no more inhibitory for endothelial ICAM-1 and VCAM-1 expression than anti-TNF-alpha alone. ICAM-1 and VCAM-1 expression at 4 h was unaffected by a combination of mAb against alpha4 and beta2 integrins, whereas expression at 24 h was significantly inhibited (p < 0.05), suggesting that the release of TNF-alpha and other cytokines involved in the initiation of the response may not require leukocyte traffic or other leukocyte functions involving these integrins. We conclude that the early up-regulation of endothelial ICAM-1 and VCAM-1 during the elicitation of contact hypersensitivity is primarily due to the immune-dependent local release of TNF-alpha. PMID- 9973426 TI - VCAM-1 expression on human dermal microvascular endothelial cells is directly and specifically up-regulated by substance P. AB - Sensory nerves in skin are capable of releasing multiple neuropeptides, which modulate inflammatory responses by activating specific cutaneous target cells. Extravasation of particular subsets of leukocytes depends upon the regulated expression of cellular adhesion molecules such as VCAM-1 on microvascular endothelial cells. We examined the direct effect of cutaneous neuropeptides on the expression and function of human dermal microvascular endothelial cell (HDMEC) VCAM-1. A significant increase in VCAM-1 immunostaining of microvascular endothelium was observed in vivo following capsaicin application to human skin. Multiple cutaneous sensory C-fiber-released neuropeptides were evaluated for their ability to induce VCAM-1 cell surface expression on HDMEC. Only substance P (SP) was found to be capable of inducing HDMEC VCAM-1 expression. This SP mediated VCAM-1 induction appeared to be a direct effect that did not require the release of other HDMEC-derived soluble factors. Increased HDMEC VCAM-1 mRNA expression was detected 1 h after the addition of SP, with peak mRNA increase at 6-9 h postinduction. FACS studies demonstrated a 6.5-fold increase in endothelial cell surface VCAM-1 expression detectable 16 h after addition of SP, which was specifically blocked by a neurokinin-1 receptor antagonist. Increased VCAM-1 cell surface expression on SP-treated HDMEC resulted in a 4-fold increase in the functional binding of 51Cr-labeled MOLT-4 T cells. These data indicate that SP is capable of directly and specifically up-regulating functional endothelial VCAM-1 expression and thus may play a key role in modulating certain inflammatory responses in the skin. PMID- 9973427 TI - IL-18 up-regulates perforin-mediated NK activity without increasing perforin messenger RNA expression by binding to constitutively expressed IL-18 receptor. AB - IL-18 is a powerful inducer of IFN-gamma production, particularly in collaboration with IL-12. IL-18, like IL-12, also augments NK activity. Here we investigated the molecular mechanism underlying the up-regulation of killing activity of NK cells by IL-18. IL-18, like IL-12, dose dependently enhanced NK activity of splenocytes. This action was further enhanced by costimulation with IL-12. Treatment with anti-IL-2R Ab did not affect IL-18- and/or IL-12-augmented NK activity, and splenocytes from IFN-gamma-deficient mice showed enhanced NK activity following stimulation with IL-12 and/or IL-18. Splenocytes from the mice deficient in both IL-12 and IL-18 normally responded to IL-18 and/or IL-12 with facilitated NK activity, suggesting that functional NK cells develop in the absence of IL-12 and IL-18. IL-18R, as well as IL-12R mRNA, was constitutively expressed in splenocytes from SCID mice, which lack T cells and B cells but have intact NK cells, and in those from IL-12 and IL-18 double knockout mice. NK cells isolated from SCID splenocytes expressed IL-18R on their surface. IL-18, in contrast to IL-12, did not enhance mRNA expression of perforin, a key molecule for exocytosis-mediated cytotoxicity. However, pretreatment with concanamycin A completely inhibited this IL-18- and/or IL-12-augmented NK activity. Furthermore, IL-18, like IL-12, failed to enhance NK activity of splenocytes from perforin deficient mice. These data suggested that NK cells develop and express IL-12R and IL-18R in the absence of IL-12 or IL-18, and that both IL-18 and IL-12 directly and independently augment perforin-mediated cytotoxic activity of NK cells. PMID- 9973428 TI - Decreased leukotriene C4 synthesis accompanies adherence-dependent nuclear import of 5-lipoxygenase in human blood eosinophils. AB - The enzyme 5-lipoxygenase (5-LO) catalyzes the synthesis of leukotrienes (LTs) from arachidonic acid (AA). Adherence or recruitment of polymorphonuclear neutrophils (PMN) induces nuclear import of 5-LO from the cytosol, which is associated with enhanced LTB4 synthesis upon subsequent cell stimulation. In this study, we asked whether adherence of human eosinophils (EOS) causes a similar redistribution of 5-LO and an increase in LTC4 synthesis. Purified blood EOS examined either in suspension or after adherence to fibronectin for 5 min contained only cytosolic 5-LO. Cell stimulation resulted in activation of 5-LO, as evidenced by its translocation to membranes and LTC4 synthesis. As with PMN, adherence of EOS to fibronectin for 120 min caused nuclear import of 5-LO. Unexpectedly, however, adherence also caused a time-dependent decrease in LTC4 synthesis: EOS adhered for 120 min produced 90% less LTC4 than did cells adhered for 5 min. Adherence did not diminish the release of [3H]AA from prelabeled EOS or reduce the synthesis of the prostanoids thromboxane and PGE2. Also, inhibition of LTC4 production caused by adherence could not be overcome by the addition of exogenous AA. Adherence increased, rather than decreased, LTC4 synthase activity. However, the stimulation of adherent EOS failed to induce translocation of 5-LO from the nucleoplasm to the nuclear envelope. This resistance to activation of the nuclear pool of 5-LO with diminished LT production represents a novel mode of regulation of the enzyme, distinct from the paradigm of up-regulated LT synthesis associated with intranuclear localization of 5-LO observed in PMN and other cell types. PMID- 9973429 TI - Activated T cells acquire endothelial cell surface determinants during transendothelial migration. AB - Activated T cells acquire endothelial cell (EC) plasma membrane constituents during transendothelial migration. This was assessed using an in vitro model system in which human peripheral blood CD4+ T cells migrated through confluent monolayers of HUVEC. Flow cytometry of migrated CD4+ T cells demonstrated that activated, but not resting, T cells acquired a variety of endothelial surface determinants, including CD31, CD49d, CD54, CD61, and CD62E. The extracellular domains of these molecules were detected on migrated T cells with mAbs, including those directed to the ligand-binding regions. A number of approaches were employed to document that the acquisition of these molecules was uniquely accomplished by activated T cells and clearly involved transfer from both resting and TNF-alpha-activated EC. Acquisition of endothelial markers by activated T cells occurred as part of the transfer of membrane components, as migrating T cells acquired EC membranes prelabeled with the lipophilic dye, 3,3' dihexadecyloxacarbocyanine perchlorate (DiOC-16), along with EC surface proteins. Thus, during transendothelial migration, activated T cells acquire endothelial membrane components, and as a result may deliver them to perivascular sites. PMID- 9973430 TI - Role of resident peritoneal macrophages and mast cells in chemokine production and neutrophil migration in acute inflammation: evidence for an inhibitory loop involving endogenous IL-10. AB - The roles played by resident macrophages (Mphi) and mast cells (MCs) in polymorphonuclear leukocyte (PMN) accumulation and chemokine production within the mouse peritoneal cavity in response to administration of zymosan (0.2 and 1 mg), LPS (1 mg/kg), and thioglycolate (0.5 ml of a 3% suspension) were investigated. A marked reduction (>95%) in intact MC numbers was obtained by pretreatment with the MC activator compound 48/80, whereas resident Mphi were greatly diminished (>85%) by a 3-day treatment with liposomes encapsulating the cytotoxic drug dichloromethylene-bisphosphonate. No modulation of thioglycolate induced inflammation was seen with either pretreatment. Removal of either MCs or Mphi attenuated LPS-induced PMN extravasation without affecting the levels of the chemokines murine monocyte chemoattractant protein-1 and KC measured in the lavage fluids. In contrast, MC depletion inhibited PMN accumulation and murine monocyte chemoattractant protein-1 and KC production in the zymosan peritonitis model. Removal of Mphi augmented the accumulation of PMN elicited by the latter stimulus. This was due to an inhibitory action of Mphi-derived IL-10 because there was 1) a time-dependent release of IL-10 in the zymosan exudates; 2) a reduction in IL-10 levels following Mphi, but not MC, depletion; and 3) an increased PMN influx and chemokine production in IL-10 knockout mice. In conclusion, we propose a stimulus-dependent role of resident MCs in chemokine production and the existence of a regulatory loop between endogenous IL-10 and the chemokine-mediated cellular component of acute inflammation. PMID- 9973431 TI - Role of p38-mitogen-activated protein kinase in spontaneous apoptosis of human neutrophils. AB - Neutrophils constitutively undergo apoptosis at both normal and inflamed sites: an important process that limits the toxic potential of the neutrophil. However, the signal pathway for neutrophil apoptosis is currently unknown. In this study, we evaluated the role of p38-mitogen-activated protein kinase (MAPK) in the spontaneous apoptosis of neutrophils in vitro. We found that p38-MAPK was constitutively tyrosine phosphorylated and activated during spontaneous apoptosis of neutrophils. Inhibition of p38-MAPK by SB203580 and an antisense oligonucleotide delayed apoptosis by approximately 24 h. The antioxidants catalase and N-acetylcysteine delayed neutrophil apoptosis, but failed to inhibit phosphorylation and activation of p38-MAPK. Granulocyte-macrophage CSF and anti Fas Ab, which altered the rate of apoptosis, did not affect phosphorylation and activation of p38-MAPK. These results suggest that the constitutive phosphorylation and activation of p38-MAPK are involved in the program of spontaneous apoptosis in neutrophils. PMID- 9973432 TI - Negative feedback between prostaglandin and alpha- and beta-chemokine synthesis in human microglial cells and astrocytes. AB - The understanding of immune surveillance and inflammation regulation in cerebral tissue is essential in the therapy of neuroimmunological disorders. We demonstrate here that primary human glial cells were able to produce alpha- and beta-chemokines (IL-8 > growth related protein alpha (GROalpha) >> RANTES > microphage inflammatory protein (MIP)-1alpha and MIP-1beta) in parallel to PGs (PGE2 and PGF2alpha) after proinflammatory cytokine stimulation: TNF-alpha + IL 1beta induced all except RANTES, which was induced by TNF-alpha + IFN-gamma. Purified cultures of astrocytes and microglia were also induced by the same combination of cytokines, to produce all these mediators except MIP-1alpha and MIP-1beta, which were produced predominantly by astrocytes. The inhibition of PG production by indomethacin led to a 37-60% increase in RANTES, MIP-1alpha, and MIP-1beta but not in GROalpha and IL-8 secretion. In contrast, inhibition of IL-8 and GRO activities using neutralizing Abs resulted in a specific 6-fold increase in PGE2 but not in PGF2alpha production by stimulated microglial cells and astrocytes, whereas Abs to beta-chemokines had no effect. Thus, the production of PGs in human glial cells down-regulates their beta-chemokine secretion, whereas alpha-chemokine production in these cells controls PG secretion level. These data suggest that under inflammatory conditions, the intraparenchymal production of PGs could control chemotactic gradient of beta-chemokines for an appropriate effector cell recruitment or activation. Conversely, the elevated intracerebral alpha-chemokine levels could reduce PG secretion, preventing the exacerbation of inflammation and neurotoxicity. PMID- 9973433 TI - Vasoactive intestinal peptide and pituitary adenylate cyclase-activating polypeptide enhance IL-10 production by murine macrophages: in vitro and in vivo studies. AB - Vasoactive intestinal peptide (VIP), a neuropeptide present in the lymphoid microenvironment, and the structurally related pituitary adenylate cyclase activating polypeptide (PACAP) act as potent anti-inflammatory agents that inhibit the function of activated macrophages and TH cells. Previous reports showed that VIP/PACAP inhibit IL-6 and TNF-alpha production in LPS-stimulated macrophages. The present study reports on the effect of VIP/PACAP on IL-10 production. Although VIP/PACAP do not induce IL-10 by themselves, they enhance IL 10 production in LPS-stimulated macrophages. The specific VPAC1 receptor mediates the stimulatory effect of VIP/PACAP, and cAMP is the major second messenger involved. VIP/PACAP increase IL-10 mRNA in LPS-stimulated cells, and the effect of transcriptional and protein synthesis inhibitors indicates de novo IL-10 production. Electromobility shift assays show that VIP/PACAP induce an increase in nuclear cAMP response element (CRE)-binding complexes, with CRE binding protein as the major active component. Treatments with either a VPAC1 antagonist or a protein kinase A inhibitor abolish IL-10 stimulation and, concomitantly, the increase in CRE binding. Effects similar to the in vitro stimulation of IL-10 were obtained in vivo in mice treated with LPS and VIP or PACAP. The neuropeptides induce increased levels of IL-10 in both serum and peritoneal fluid, and increased expression of the IL-10 mRNA in peritoneal exudate cells. The stimulation of IL-10 production in activated macrophages represents a novel anti-inflammatory activity of VIP and PACAP, which presumably acts in vivo in conjunction with the inhibition of proinflammatory cytokines such as IL-6 and TNF alpha to reduce the magnitude of the immune response. PMID- 9973434 TI - Resistance to Fas-mediated T cell apoptosis in asthma. AB - Over activation of CD4+ T cells in the peripheral blood and airway tissues is characteristic of asthma; therefore, we investigated whether activated T cells from asthmatic subjects have altered apoptotic potential through the Fas death receptor. We found that mitogen-stimulated peripheral blood T cells of asthmatic subjects expressed cell surface Fas, but failed to undergo the normal degree of apoptosis after Fas receptor ligation. T cells from asthmatics exhibited normal apoptotic responses to gamma-irradiation (dependent on IL-1 converting enzyme family proteases), ceramide, and mitogen challenge, suggesting functional integrity of the apoptotic pathway. Furthermore, the defect in Fas-dependent apoptosis was overcome by prestimulation with allogeneic accessory cells instead of mitogen. Taken together, the findings suggest that selective resistance to Fas dependent apoptosis reflects altered Ag-driven, accessory cell-dependent signaling and that ineffective activation of Fas signal transduction may contribute to T cell-dependent immunoinflammation in asthma. PMID- 9973435 TI - A transgenic model to analyze the immunoregulatory role of IL-10 secreted by antigen-presenting cells. AB - IL-10 is a cytokine secreted by a wide variety of cells type that has pleiotropic stimulatory and suppressive activities on both lymphoid and myeloid cells in vitro. To analyze the consequences of high IL-10 secretion by APCs in immune responses, we produced transgenic mice expressing human IL-10 directed by the MHC class II Ea promoter. Despite alterations in the development of T and B cells, no gross abnormalities were detected in peripheral lymphocyte populations or serum Ig levels. However, when immunized using conditions that give either a Th2-type or a Th1-type response, IL-10 transgenic mice failed to mount a significant T or B cell immune response to OVA. IL-10 transgenic mice were also highly susceptible to infection with intracellular pathogens like Listeria monocytogenes or Leishmania major, in contrast to IL-10 transgenic mice, where the transgene was express in T cells. Finally, the recently described stimulatory effect of IL-10 on CD8+ T cells was confirmed by the ability of IL-10 transgenic mice to limit the growth of immunogenic tumors by a CTL-mediated mechanism. These results demonstrate, that, depending on the type of immune response, IL-10 can mediate immunosuppressive or immunostimulatory activities in vivo. PMID- 9973436 TI - A hsp70-2 mutation recognized by CTL on a human renal cell carcinoma. AB - We performed T cell cloning experiments with a tumor-infiltrating lymphocyte subpopulation derived from a renal cell carcinoma tumor site (RCC-7) in which the TCR clonotypic repertoire had been analyzed in terms of TCRBV complementarity determining region 3 size distribution. We report in this work the characterization of one of the five RCC-specific MHC class I-restricted CTL clones isolated in RCC-7. This TCRBV6J1S1 CTL recognized only the autologous RCC 7 tumor cell line in the context of HLA-A*0201, and the Ag is encoded by a mutated form of the hsp70-2 gene found in the tumor cells, but not in autologous PBLs nor in 47 other tumors. The identification of this gene was achieved by cotransfecting into COS cells a cDNA library of RCC-7 together with HLA-A*0201. Transfectants expressing the Ag were identified by their ability to stimulate TNF release by the CTL clone. The antigenic peptide is a decamer with a mutated residue at position 8. Half-maximal lysis was obtained with only 5 x 10(-11) M of decapeptide in target sensitization assays compared with 5 x 10(-8) M for the wild-type decapeptide. This difference in recognition was not related to difference in binding HLA-A*0201-presenting molecules, as assessed in an immunofluorescence-based peptide-binding assay using T2 cells. Constitutive hsp70 expression in various tumors suggests that this stress-induced protein may be recognized in situ by tumor-infiltrating lymphocytes. The finding in the tumor of a mutated form of the stress-induced hsp70-2 gene whose product is specifically recognized by TILs with high avidity is discussed in view of the present use of mycobacteria or heterologous heat-shock proteins as immunomodulators or as subunit vaccine candidates. PMID- 9973437 TI - Novel HLA-Cw8-restricted T cell epitopes derived from tyrosinase-related protein 2 and gp100 melanoma antigens. AB - The identification of T cell epitopes presented by alternative HLA-B and -C alleles may provide a means to counteract the tumor escape mechanism based on the selection of tumor cells no longer susceptible to HLA-A-restricted T cell recognition. Several T cell clones and lines were obtained from T lymphocytes purified from melanoma-infiltrated or noninfiltrated lymph nodes of a patient who remained disease free 8 yr after surgery. Selected T cells recognized the autologous melanoma as evaluated by direct cytolysis and production of cytokines. These effectors were directed against the tyrosinase-related protein-2 (TRP-2) and gp100 melanoma epitopes restricted by HLA-Cw8. The nonamer and decamer peptides containing the sequence ANDPIFVVL (residues 387-395) of TRP-2 and the octamer, nonamer, and decamer peptides containing the sequence SNDGPTLI (residues 71-78) of gp100 reconstituted the epitope for TRP-2- and gp100-specific T cell lines and clones, respectively. However, only the nonameric form of TRP-2 and the nonameric and octameric forms of gp100 were able to induce peptide-specific T cells recognizing the autologous tumor in an HLA-class I-restricted fashion from PBMC of the melanoma patient studied. Together these data indicate that HLA-Cw8 can restrict the recognition of gp100 and TRP-2 epitopes by CTL, and that such peptides could stimulate a patient's PBL, suggesting that these Ags could have contributed to a systemic immunity against melanoma. PMID- 9973438 TI - Changes in the fine specificity of gp100(209-217)-reactive T cells in patients following vaccination with a peptide modified at an HLA-A2.1 anchor residue. AB - In a recent clinical trial, HLA-A2+ melanoma patients were vaccinated with a peptide derived from the melanoma Ag gp100, which had been modified at the second position (g9-209 2M) to enhance MHC binding affinity. Vaccination led to a significant increase in lymphocyte precursors in 10 of 11 patients but did not result in objective cancer responses. We observed that some postvaccination PBMC cultures were less reactive with tumor cells than they were with g9-209 peptide pulsed T2 cells. In contrast, g9-209-reactive tumor-infiltrating lymphocyte cultures generally reacted equally with tumor cells and g9-209 peptide-pulsed T2 cells. To investigate this difference in T cell reactivity, T cell cloids derived from the PBMC of three patients vaccinated with g9-209 2M were compared with T cell cloids isolated from g9-209-reactive TIL cultures. All of the T cell cloids obtained from TIL reacted with HLA-A2+, gp100+ melanoma cell lines as well as with g9-209 and g9-209 2M peptide-pulsed targets. In contrast, only 3 of 20 PBMC derived T cell cloids reacted with melanoma cell lines in addition to g9-209 and to g9-209 2M peptide-pulsed targets. Twelve of twenty PBMC-derived cloids reacted with g9-209 and g9-209 2M peptide-pulsed targets but not with melanoma cell lines. And 5 of 20 PBMC-derived cloids recognized only the g9-209 2M-modified peptide-pulsed targets. These results suggest that immunizing patients with the modified peptide affected the T cell repertoire by expanding an array of T cells with different fine specificities, only some of which recognized melanoma cells. PMID- 9973439 TI - Biased TCR repertoire in infiltrating lesional T cells in human Bancroftian filariasis. AB - To investigate the hypothesis that T cells recognizing specific Ags localize to the site of disease activity in human bancroftian filariasis, we have compared the repertoire of TCR Vbeta gene segments in lesions vs blood in individual patients by RT-PCR ELISA. Vbeta14 and Vbeta24 were overrepresented (5% greater in tissue compared with PBMCs and/or tissue/PBMC ratios in the highest 5% of all tissue/PBMC ratios for all Vbetas for all subjects) in 50% and 40% of study subjects, respectively. Overrepresentation of these two Vbetas did not occur in any control subject. In comparing three patient groups, the proportion of individuals meeting at least one criterion for Vbeta14 overrepresentation was shown to increase in tandem with our current concepts of disease progression (asymptomatic filariasis = 25%; clinical filariasis with active infection = 60%; clinical filariasis without active infection = 71%). In 6 of the 10 individuals with Vbeta14 overrepresentation, Vbeta14 represented >20% of the entire lesional Vbeta repertoire. All but one of the 20 study subjects had at least one Vbeta gene segment that was overrepresented in tissue compared with PBMCs. Only a small number of Vbetas, usually three or less, were overrepresented in any single filariasis patient. However, in the same tissue, no differences between patient groups were found when IFN-gamma, TNF-alpha, IL-4, IL-5, and IL-12 mRNA expression were examined. Taken together, these findings suggest that, in principle, in essentially all patients, whether with subclinical or with clinical filariasis, distinct and limited T cell populations are concentrated in affected tissue. PMID- 9973440 TI - Direct analysis of viral-specific CD8+ T cells with soluble HLA-A2/Tax11-19 tetramer complexes in patients with human T cell lymphotropic virus-associated myelopathy. AB - Human T cell lymphotropic virus-I (HTLV-I)-associated myelopathy is a slowly progressive neurologic disease characterized by inflammatory infiltrates in the central nervous system accompanied by clonal expansion of HTLV-I-reactive CD8+ T cells. In patients carrying the HLA-A2 allele, the immune response is primarily directed to the Tax11-19 peptide. The frequency, activation state, and TCR usage of HLA-A2/Tax11-19 binding T cells in patients with HTLV-I-associated myelopathy was determined using MHC class I tetramers loaded with the Tax11-19 peptide. Circulating Tax11-19-reactive T cells were found at very high frequencies, approaching 1:10 circulating CD8+ T cells. T cells binding HLA-A2/Tax11-19 consisted of heterogeneous populations expressing different chemokine receptors and the IL-2R beta-chain but not the IL-2R alpha-chain. Additionally, Tax11-19 reactive CD8+ T cells used one predominant TCR Vbeta-chain for the recognition of the HLA-A2/Tax11-19 complex. These data provide direct evidence for high frequencies of circulating Tax11-19-reactive CD8+ T cells in patients with HTLV-I associated myelopathy. PMID- 9973441 TI - Integrin engagement regulates proliferation and collagenase expression of rheumatoid synovial fibroblasts. AB - Growth of and metalloproteinase production by fibroblast-like synoviocytes (FLSs) in patients with rheumatoid arthritis (RA) contribute to cartilage and bone destruction associated with development of the expanding inflammatory tissue referred to as pannus. Increased levels of extracellular matrix (ECM) proteins in the pannus suggest that intracellular signals generated through integrin receptors might control these processes. We developed a cell culture system permitting accurate assessment of the effect of cell adhesion to various ECM proteins on FLS phenotype. We show that FLS proliferation to platelet-derived growth factor requires a second signal provided by adhesion to an ECM protein. Fibronectin, vitronectin, collagen, or laminin could provide the second signal and was similarly required for the proliferation of FLSs from RA or osteoarthritis patients. Adhesion to fibronectin, collagen, or Arg-Gly-Asp peptide down-regulated collagenase expression. Primarily alphav integrin receptors mediated this down-regulation upon adhesion to fibronectin. Loss of cell adhesion and TNF-alpha stimulation synergistically increased collagenase expression. Increased collagenase expression upon nonadherence was mimicked by treatment with cytochalasin B, suggesting that the loss of cytoskeletal structure associated with a change in cell shape mediates increased collagenase in nonadherent cells. Thus, although increased fibronectin in the lining layer in RA might be expected to inhibit collagenase expression, the change in cell shape associated with this multilayer structure might actually lead to increased collagenase expression. PMID- 9973442 TI - Frequency of class I HLA-restricted anti-HIV CD8+ T cells in individuals receiving highly active antiretroviral therapy (HAART). AB - Peptide/MHC tetrameric complexes were used to enumerate the frequency of HLA class I-restricted epitope-specific CD8+ T cells in 18 HLA-A*0201 HIV type 1 infected asymptomatic patients. HLA-A*0201 molecules were complexed to HIV Gag p17 (amino acids 77-85) and reverse transcriptase (amino acids 464-472) peptides, biotinylated, and bound to streptavidin-phycoerythrin to form tetramers. We show in this study that 17 of 18 HIV-1-infected asymptomatic patients have circulating frequencies of 1/50-1/1000 CD8+ T cells that recognize both Gag and Pol CTL epitopes or either epitope alone. The functional nature of these cells is open to interpretation, as we show that despite relatively high frequencies of fresh epitope-specific CD8+ T cells, variant epitope sequences in viral plasma progeny were rare. In addition, the majority of tetramer-positive cells did not display discernible fresh CTL activity; only after restimulation with specific peptide in culture was there an expansion of epitope-specific CD8+ cells, correlating with high CTL activity. These data suggest that fresh tetramer-stained cells probably represent memory precursors; we demonstrate, with the application of highly active antiretroviral therapy, that the interruption of chronic antigenic stimulation causes significant reductions in the frequency of these cells in five of six patients. In conclusion, this study provides evidence that persistently replicating viral populations are probably required to maintain high frequencies of HIV-1 epitope-specific CD8+ T cells in asymptomatic chronically infected individuals PMID- 9973443 TI - Immune-mediated destruction of melanocytes in halo nevi is associated with the local expansion of a limited number of T cell clones. AB - The beta-chain repertoire of the T cells that infiltrate spontaneously regressing nevi (the halo nevus phenomenon) was studied. In addition to the infiltration of the halo nevi by cutaneous lymphocyte-associated Ag-positive lymphocytes, oligoclonal expansion of T cells was observed in all halo nevi of all patients. T cells using the same TCR beta-chain were observed in distinct halo nevi of the same patient but not in his peripheral blood, demonstrating a local expansion of common clones that are most likely activated by the Ag(s) shared by independent halo nevi of the same patient. PMID- 9973444 TI - Signs of immaturity of splenic dendritic cells from the autoimmune prone biobreeding rat: consequences for the in vitro expansion of regulator and effector T cells. AB - From the biobreeding-diabetic prone (BB-DP) rat, an animal model for endocrine autoimmunity, phenotype and function of splenic dendritic cells (DC) were studied. Furthermore, the suppressive effect of peritoneal macrophages (pMphi) from the BB-DP rat in the MLR was investigated. Lower numbers of splenic DC were isolated from BB-DP rats than from control Wistar rats. In the preautoimmune phase, DC of the BB-DP rat had a lower surface MHC class II expression (and in preliminary data, a lower CD80 expression), ingested more bacteria, and had a lower stimulatory potency in the syngeneic (syn)MLR as compared with control DC. During disease development, the MHC class II expression further decreased, and a low stimulatory activity became evident in the allogeneic (allo)MLR. With regard to the expansion of suppressor/regulatory T cells, a lower percentage of RT6+ T cells but higher percentages of CD45RClow T cells were induced by BB-DP DC in synMLR, but not in alloMLR. An increase in the CD4/CD8 T cell ratio was observed in both the syn- and alloMLR due to a relative weak expansion of CD8+ T cells with DC of the BB-DP rat. Resident pMphi isolated from BB-DP or Wistar rats were equally effective in suppressing the DC-driven synMLR. In conclusion, splenic DC from the BB-DP rat have a lower accessory cell function already at young age, before the development of disease, and expanded different subsets of effector/suppressor T cells in vitro as compared with those from Wistar rats. The dysfunction of DC from BB-DP rats is likely to be caused by their relative immaturity as indicated by their low class II and costimulatory molecule expression and relatively high phagocytic activity. PMID- 9973445 TI - Mimicry between the hepatitis B virus DNA polymerase and the antigenic targets of nuclear and smooth muscle antibodies in chronic hepatitis B virus infection. AB - Autoantibodies to nuclear and smooth muscle are common in hepatitis B virus (HBV) infection. To understand their origin, we scanned protein databases and found that HBV-DNA polymerase (HBV-pol) shares 7-9 amino acid sequences with nuclear (MHC II trans-activator, nuclear pore core protein, nuclear mitotic apparatus, and polymyositis sclerosis Ag) and smooth muscle proteins (caldesmon and myosin). Twenty-mer peptides with relevant homologues and an irrelevant control peptide were constructed and ELISAs were established. Sixty-five children with chronic HBV infection, 104 patients with other chronic liver diseases (CLD), 36 patients with extrahepatic autoimmune diseases, and 24 healthy controls were investigated. Double reactivity to HBV-pol peptides and corresponding self homologues was observed in 40% of HBV-positive patients as compared with four (4%) with other chronic liver diseases, two (6%) with extrahepatic autoimmune diseases, and in none of the healthy controls (p < 0.001 for all). Double reactivity to myosin or caldesmon peptides and their HBV-pol homologues was associated with anti-smooth muscle Ab positivity by immunofluorescence (p < 0.05 for both). HBV-positive sera double reactive for myosin or caldesmon and their homologous HBV-pol peptides also reacted with the native proteins on immunoblot. Fifty to ninety percent Ab inhibition to individual HBV-pol and HBV-pol99-118 peptides was noted by preincubation with individual HBV-pol/self homologue peptide and native proteins, respectively, but not with control peptide. Our results show that cross-reactive immunity targeting homologous sequences of viral and self proteins may partly account for autoantibody production in HBV infection. PMID- 9973446 TI - Identification of autoimmune T cells among in vivo expanded CD25+ T cells in multiple sclerosis. AB - Although clonal expansion of autoimmune T cells has been reported in multiple sclerosis (MS), very limited information is available on specificities, clonal size, or activation state of the expanded clones. Here we address the issue of clonal expansion by using a novel technique demonstrating clonotypes defined by single-strand conformation polymorphism of TCR beta-chain cDNAs. Examination of activated T cells (CD3+CD25+) isolated from the peripheral blood of MS revealed limited numbers (20 approximately 82) of expanded clones defined by single-strand conformation polymorphism clonotype. To estimate the Ag specificities of dominant clonotypes in the activated T cells, these samples were examined in parallel with Th1 T cell clones specific for myelin basic protein or proteolipid protein (PLP) derived from the same patients. Analysis of two patients demonstrated that the dominant clonotypes would contain those specific for myelin basic protein or PLP. Although the majority of the clonotypes could be detected only transiently, a PLP95-116-specific clonotype was found to persist for over 1 yr. Thus, single strand conformation polymorphism clonotype analysis allows us to monitor the kinetics of given T cell clones in vivo and could provide useful information for designing clonotype (Id)-specific manipulation of human diseases such as MS. PMID- 9973448 TI - A re-evaluation of the frequency of CD8+ T cells specific for EBV in healthy virus carriers. AB - EBV is a gammaherpesvirus that can establish both nonproductive (latent) and productive (lytic) infections within the cells of its host. Although T cell responses to EBV latent proteins have been well characterized, little is known about the importance of responses to lytic proteins in long term virus carriers. Here we have compared the frequencies of CD8+ T cells specific for EBV latent and lytic Ags in healthy virus carriers, using three techniques: limiting dilution analysis, enzyme-linked immunospot assay, and FACS staining with tetrameric MHC peptide complexes. T cells specific for EBV lytic protein epitopes were readily detectable in all donors and were usually more abundant than those specific for latent epitopes. We infer that direct T cell control of viral replicative lesions is maintained in long term carriers of EBV and is an important component of the immune response to this virus. Estimates of CD8+ T cell frequencies varied considerably according to methodology; values obtained from MHC-peptide tetramer staining were, on the average, 4.4-fold higher than those obtained from enzyme linked immunospot assays, which were, in turn, on the average, 5.3-fold higher than those obtained from limiting dilution analysis. Tetramer staining showed that as many as 5.5% circulating CD8+ T cells in a virus carrier were specific for a single EBV lytic protein epitope. Such values are much greater than previously imagined and illustrate how antigenic challenge from a persistent herpesvirus can influence the composition of the host's CD8+ T cell pool. PMID- 9973447 TI - Blocking OX-40/OX-40 ligand interaction in vitro and in vivo leads to decreased T cell function and amelioration of experimental allergic encephalomyelitis. AB - The OX-40R is a member of the TNF receptor family and is expressed primarily on activated CD4+ T cells. When the OX-40R is engaged by the OX-40 ligand (OX-40L), a potent costimulatory signal occurs. We have identified a population of CD11b+ cells, isolated from the central nervous system (CNS) of mice with actively induced experimental allergic encephalomyelitis (EAE), that expresses OX-40L. Moreover, the expression of OX-40L was found to be associated with paralytic episodes of EAE and was reduced or absent at disease recovery. These CD11b+ cells also coexpressed B7 and MHC class II. Therefore, to address the relative contributions of OX-40R/OX-40L and CD28/B7 to the costimulation of myelin specific T cells, blocking studies were performed using soluble OX-40R and/or soluble CTLA-4. CD11b+ cells isolated from the CNS of mice with actively induced EAE were able to present Ag to proteolipid protein 139-151-specific T cell lines in vitro. The addition of soluble OX-40R:Ig to CD11b+ brain microglia/macrophages inhibited T cell proliferation by 50-70%. The addition of CTLA-4:Ig inhibited T cell proliferation by 20-30%, and the combination inhibited T cell proliferation by 95%. In vivo administration of soluble OX-40R at the onset of actively induced or adoptively transferred EAE reduced ongoing signs of disease, and the mice recovered more quickly from acute disease. The data imply that OX-40L, expressed by CNS-derived APC, acts to provide an important costimulatory signal to EAE effector T cells found within the inflammatory lesions. Furthermore, the data suggest that agents designed to inhibit the OX-40L/OX-40R complex may be useful for treating autoimmune disease. PMID- 9973449 TI - An altered peptide ligand specifically inhibits Th2 cytokine synthesis by abrogating TCR signaling. AB - Altered peptide ligands (APL) can modify T cell effector function by their diversity in binding to the TCR or MHC class II-presenting molecules. The capacity to inhibit Th2 cytokine production by allergen-specific T cells would contribute to combating allergic inflammation. The presence of APL generated by Ala-substitutions in a synthetic dodeca-peptide spanning an immunodominant epitope of bee venom phospholipase A2 (PLA) was investigated in human T cells. Four of five substituted peptides reduced proliferation, IL-4, and IFN-gamma production by cloned PLA-specific Th0 cells proportionately. However, one APL, PLA-F82A, inhibited IL-4 but had no effect on IFN-gamma production. This uncoupling of IL-4 from IFN-gamma production was also observed on immunogenic restimulation of the cloned T cells pre-exposed to the APL/APCs. It appeared to result from lower affinity of binding to MHC class II by the APL compared with the native peptide. The APL also inhibited IL-4 production by polyclonal T cells. In consequence of the change in cytokine secretion, the production of IgG4 in vitro increased by PLA-F82A stimulation, compared with the native peptide. Exposure of the cloned T cells to either the APL or the native peptide, in the absence of professional APC, induced anergy such that proliferation and production of IL-4, IL-5, and IL-13 was abrogated on immunogenic rechallenge. Defective T cell activation appeared to result from alterations in transmembrane signaling through the TCR, specifically to lack of tyrosine phosphorylation of the tyrosine kinase, ZAP-70. PMID- 9973450 TI - Clonal expansion of CD4+ TCRbetabeta+ T cells in TCR alpha-chain- deficient mice by gut-derived antigens. AB - A population of CD4+ alpha-beta+ T cells increases in the mucosal and peripheral lymphoid tissues of TCRalpha-chain-deficient mice with inflammatory bowel disease. The alpha-beta+ T cells, which produce predominantly IL-4, mediate the proliferation of colonic epithelial crypts and the infiltration of large numbers of IgA-producing plasma cells into the lamina propria of the colon. To examine whether enteric Ags were recognized by a population of monoclonal alpha-beta+ T cells leading to the intestinal inflammation, we examined the usage and clonotypes of TCR expressed by the alpha-beta+ T cells in TCRalpha-chain deficient mice with inflammatory bowel disease. Analyses of immunoprecipitates by two dimensional electrophoresis and single-cell RT-PCR revealed that TCR of the alpha-beta+ T cells was a homodimer of beta-chains that was capable of recognizing luminal bacterial Ags. PCR single-strand conformation polymorphism analysis of TCR Vbeta transcripts revealed monoclonal accumulation of the alpha beta+ T cells in the colonic lamina propria of the diseased mice. DNA sequencing revealed the accumulation of the alpha-beta+ T cells with the same CDR3 sequences in the colon. These findings suggest that the pathogenic CD4+ alpha-beta+ T cells expressing a homodimeric form of the TCRbeta-chains can be clonally expanded upon the stimulation with gut-derived Ags. PMID- 9973451 TI - CD1 expression by dendritic cells in human leprosy lesions: correlation with effective host immunity. AB - A potential role for the CD1 family of lipid Ag-presenting molecules in antimicrobial immunity in vivo was investigated in human leprosy skin lesions. Strong induction of three CD1 proteins (CD1a, -b, and -c) was observed in dermal granulomas in biopsy samples of involved skin from patients with the tuberculoid form of leprosy or with reversal reactions, which represent clinical patterns of disease associated with active cellular immunity to Mycobacterium leprae. In contrast, lesions from patients with the lepromatous form of the disease who lack effective cell-mediated immunity to the pathogen did not show induction of CD1 proteins. Thus, expression of CD1 correlated directly with effective immunity to M. leprae, as assessed by the clinical course of infection. CD1a, -b, and -c could be induced to similar levels on monocytes from the blood of either tuberculoid or lepromatous leprosy patients. This suggested that the absence of expression in lepromatous lesions was most likely due to local factors at the site of infection as opposed to a primary defect of the CD1 system itself. The majority of cells expressing CD1 in leprosy lesions were identified as a population of CD83+ dendritic cells. Initial in vitro studies of the Ag presenting function of CD1+CD83+ monocyte-derived dendritic cells showed that such cells were highly efficient APCs for CD1-restricted T cells. These results indicate that the CD1 system can be up-regulated in human infectious diseases in vivo, and may play a role in augmenting host defense against microbial pathogens. PMID- 9973452 TI - B7.2 has opposing roles during the activation versus effector stages of experimental autoimmune thyroiditis. AB - APCs provide costimulatory and down-regulatory signals to Ag-activated T cells through interactions between B7.1 and B7.2 on APCs with either CD28 or CTL Ag-4 expressed on T cells. Recipients of mouse thyroglobulin (MTg)-primed spleen cells activated in the presence of anti-B7.2 had decreased experimental autoimmune thyroiditis (EAT) severity compared with recipients of cells cultured with control rat Ig or anti-B7.1. Blocking B7.2 during in vivo priming also suppressed the ability of MTg-primed spleen cells to transfer EAT, implicating a role for B7.2 for priming and in vitro activation of EAT effector cells. In contrast, administration of anti-B7.2 or anti-B7.2 Fab to recipients of MTg-activated spleen cells increased the severity of EAT compared with recipients receiving control Ig. Thyroids from anti-B7.2-treated recipients had increased expression of IL-4 mRNA compared with thyroids from rat Ig-treated controls. Both B7.1 and B7.2 molecules were expressed in the thyroids of mice with EAT, although B7.2 was more prevalent than B7.1. Administration of both anti-B7.1 and anti-B7.2 to recipient mice suppressed the development of EAT, while anti-B7.1 treatment alone had no effect on EAT severity. The suppression of EAT was not observed when anti B7.1 and anti-B7.2 treatment was delayed until 7 days after cell transfer, suggesting a requirement for B7 in the initiation of EAT in recipient mice. These results suggest that costimulation is required during the effector phase of EAT and that B7.2 may have opposing roles in the activation versus effector stages of autoreactive T cells. PMID- 9973453 TI - Cutting edge: the CD45 tyrosine phosphatase is an inhibitor of Lck activity in thymocytes. AB - A widely accepted model for regulation of the Lck tyrosine kinase is that it is activated by CD45-mediated dephosphorylation of its COOH-terminal negative regulatory tyrosine (Tyr505). Previous work from our laboratory, however, found that despite hyperphosphorylation of Tyr505, the activity of Lck from CD45- T cell lines was actually increased due to hyperphosphorylation of the positive regulatory tyrosine, residue 394. To avoid potential complications introduced by transformed cells, in this study we have characterized the effect of CD45 on Lck activity in normal cells. Lck in thymocytes from CD45-/- mice was hyperphosphorylated on tyrosine residues. Importantly, and in disagreement with the model that CD45 only activates Lck in vivo, the kinase activity of Lck from cells lacking CD45 was substantially increased. These results support a model in which CD45 dephosphorylates both Tyr505 and Tyr394, the net effect in normal thymocytes being a decrease in enzymatic activity. PMID- 9973454 TI - Cutting edge: chronic intestinal inflammation in STAT-4 transgenic mice: characterization of disease and adoptive transfer by TNF- plus IFN-gamma producing CD4+ T cells that respond to bacterial antigens. AB - We generated transgenic mice for STAT-4, a regulatory protein specifically associated with IL-12 signaling, under the control of a CMV promoter. These mice expressed strikingly increased nuclear STAT-4 levels in lamina propria CD4+ T lymphocytes upon systemic administration of dinitrophenyl-keyhole limpet hemocyanin and developed chronic transmural colitis characterized by infiltrates of mainly CD4+ T lymphocytes. The latter cells produced predominantly TNF and IFN gamma but not IL-4 upon activation with alphaCD3/CD28 or autologous bacterial Ags, consistent with a Th1-type cell response. Furthermore, chronic colitis in STAT-4 transgenic mice could be adoptively transferred to SCID mice by colonic and splenic CD4+ T cells that were activated with Ags from autologous bacterial flora. These data establish a critical molecular signaling pathway involving STAT 4 for the pathogenesis of chronic intestinal inflammation, and targeting of this pathway may be relevant for the treatment of colitis in humans. PMID- 9973455 TI - Fas ligand and Fas are expressed constitutively in human astrocytes and the expression increases with IL-1, IL-6, TNF-alpha, or IFN-gamma. AB - Fas ligand (FasL) and Fas are mediators of apoptosis, which are implicated in the peripheral deletion of autoimmune cells, activation-induced T cell death, and cytotoxicity mediated by CD8+ T cells. Fas is also believed to be involved in several central nervous system diseases, but until now, the effector cells expressing FasL in the brain have not been identified. We investigated the expression levels of Fas and FasL with the stimulation of cytokines and the possible effector cells targeting Fas-bearing cells. Our data demonstrated that: 1) FasL is expressed constitutively on astrocytes taken from a fetus or an adult and that its expression increases when these cells are treated with IL-1, IL-6, or TNF-alpha in which the pretreatment of IFN-gamma triggers astrocytes to express more FasL; 2) astrocytes induce apoptosis in MOLT-4 cells through FasL; 3) Fas is also expressed constitutively and is up-regulated by IL-1, IL-6, or TNF alpha in which the pretreatment of IFN-gamma triggers astrocytes to express more Fas; 4) apoptosis occurs when fetal astrocytes are treated with agonistic anti Fas IgM Ab after culture with IFN-gamma and TNF-alpha; and 5) TNF-related apoptosis inducing ligand is up-regulated in fetal astrocytes with stimuli of IL 1 or TNF-alpha. These findings suggest a possible role of astrocytes in the induction of apoptosis in central nervous system diseases. PMID- 9973456 TI - Differential effects of IL-2 and IL-15 on the death and survival of activated TCR gamma delta+ intestinal intraepithelial lymphocytes. AB - TCR gamma delta+ cells are enriched in the intestine mucosa and constitute approximately half of the intestinal intraepithelial lymphocytes (iIEL) in mice. They are likely activated by self and foreign Ags in situ, but little is known about how the activated gamma delta iIEL are regulated. In the iIEL compartment, IL-2 is produced by activated TCR alpha beta+ iIEL, and IL-15 message is detected in iIEL and in the epithelial cells. We found surface expression of IL-2 as well as IL-15Rs on activated gamma delta iIEL, and examined the effects of IL-2 and IL 15 on the survival and death of gamma delta iIEL during secondary stimulation through TCR. We found that both cytokines supported growth of the restimulated gamma delta iIEL, but exerted different effects on their survival. A significant higher number of live cells were recovered from the gamma delta iIEL cultures restimulated in IL-15 than in IL-2. Quantitation of apoptotic cells showed more cell death in the IL-2 group than in the IL-15 group. The cell death was associated with restimulation through TCR and was not caused by insufficient growth factor, thus representing activation-induced cell death. Western blot analyses found no difference in the levels of Bcl-2 and Bax proteins between the two groups. However, the level of Bcl-xL protein diminished with time in the IL-2 group whereas the level was sustained in the IL-15 group, which may contribute to the pro-survival effect of IL-15. These results demonstrated that the survival of activated gamma delta iIEL is differentially regulated by IL-2 and IL-15. PMID- 9973457 TI - Mucosally induced systemic T cell unresponsiveness to ovalbumin requires CD40 ligand-CD40 interactions. AB - CD40 ligand (CD40L) gene-disrupted (CD40L-/-) mice were employed to examine the role of costimulatory signals via CD40L-CD40 interactions in mucosally induced tolerance. CD40L-/- and control (CD40L+/+) mice of the same C57BL/6 x 129/J background were immunized orally with 25 mg of OVA before systemic challenge with OVA in CFA. While CD40L+/+ mice showed reductions in Ag-specific T cell responses including delayed-type hypersensitivity (DTH) and proliferative responses, CD40L /- mice underwent normal T cell responses. Further, cytokine analysis of splenic CD4+ T cells showed that both Th1-type (e.g., IFN-gamma and IL-2) and Th2-type (e.g., IL-4, IL-5, IL-6, and IL-10) responses were maintained in CD40L-/- mice orally immunized with OVA, whereas these cytokine responses in CD40L+/+ mice were significantly reduced. In addition, splenic CD4+ T cells from CD40L-/- mice orally immunized with OVA provided B cell help in Ag-specific Ab-forming cells when the cells were cultured with naive B cells in the presence of Ag and CD40L transfected cell lines. In contrast, an identical culture condition containing splenic CD4+ T cells from orally tolerized CD40L+/+ mice did not exhibit helper activity. Taken together, these findings indicate that CD40L and CD40 interactions are essential for the induction of systemic T cell unresponsiveness to orally administered Ag. PMID- 9973458 TI - Direct delivery of the Bordetella pertussis adenylate cyclase toxin to the MHC class I antigen presentation pathway. AB - Among bacterial toxins, the adenylate cyclase toxin of Bordetella pertussis (CyaA) has a unique mechanism of entry that consists in the direct translocation of its catalytic domain across the plasma membrane of target cell, a mechanism supposed to be independent of any endocytic pathway. Here, we report that the CyaA toxin is delivered to the cytosolic pathway for MHC class I-restricted Ag presentation. Using peritoneal macrophages as APC, we show that the OVA 257-264 CD8+ epitope genetically inserted into a detoxified CyaA (CyaA-OVA E5) is presented to CD8+ T cells by a mechanism requiring 1) proteasome processing, 2) TAP, and 3) neosynthesis of MHC class I. We demonstrate that the presentation of CyaA-OVA E5, like the translocation of CyaA into eukaryotic cells, is dependent on extracellular Ca2+ and independent of vacuolar acidification. Moreover, inhibitors of the phagocytic and macropinocytic endocytic pathways do not affect the CyaA-OVA E5 presentation. The absence of specific cellular receptors for CyaA correlates with the ability of various APC to present the recombinant CyaA toxin, including dendritic cells, macrophages, splenocytes, and lymphoid tumoral lines. Taken together, our results show that the CyaA presentation pathway is not cell type specific and is unrelated to a defined type of endocytic mechanism. Thus, it represents a new and unconventional delivery of an exogenous Ag into the conventional cytosolic pathway. PMID- 9973459 TI - A genome-wide search identifies two susceptibility loci for experimental autoimmune encephalomyelitis on rat chromosomes 4 and 10. AB - Experimental autoimmune encephalomyelitis (EAE) is an autoimmune disease of the central nervous system that exhibits many pathologic similarities with multiple sclerosis. The genetic loci that contribute to mononuclear cell infiltration of the central nervous system and clinical manifestations of EAE in the rat were investigated in the F2 progeny of the highly susceptible Lewis and resistant Brown Norway strains. The data confirmed that the Lewis allele of a MHC-linked gene is necessary, but not sufficient, to confer EAE susceptibility in the F2 progeny. Subsequent analyses were thus restricted to the subset of the F2 animals with EAE-predisposing MHC genotypes. A genome-wide scan approach was performed using 103 microsatellite markers covering 85% of the genome. Two non-MHC regions were identified, one near the centromere of chromosome 4 and the other on the long arm of chromosome 10, that significantly contributed to the disease. In addition, three regions on chromosomes 9, 13, and 17 were suggestive for linkage. Congenic mapping is now needed to reduce the support intervals encoding the loci of interest to sizes amenable to physical mapping and to eventually demonstrate the involvement of some of the candidate genes of immunologic importance localized in these regions. PMID- 9973460 TI - TCR-independent pathways mediate the effects of antigen dose and altered peptide ligands on Th cell polarization. AB - We examined the role of the peptide/MHC ligand in CD4+ T cell differentiation into Th1 or Th2 cells using a TCR alphabeta transgenic mouse specific for hemoglobin (Hb)(64-76)/I-Ek. We identified two altered peptide ligands of Hb(64 76) that retain strong agonist activity but, at a given dose, induce cytokine patterns distinct from the Hb(64-76) peptide. The ability of these peptides to produce distinct cytokine patterns at identical doses is not due to an intrinsic qualitative property. Each peptide can induce Th2 cytokines at low concentrations and Th1 cytokines at high concentrations and has a unique range of concentrations at which these distinct effects occur. The pattern of cytokines produced from limiting dilution of naive T cells demonstrated that the potential to develop an individual Th1 or Th2 cell is stochastic, independent of Ag dose. We propose that the basis for the observed effects on the Th1/Th2 balance shown by the altered peptide ligands and the amount of Ag dose involves the modification of soluble factors in bulk cultures that are the driving force that polarize the population to either a Th1 or Th2 phenotype. PMID- 9973461 TI - Regulation of cell survival during B lymphopoiesis: apoptosis and Bcl-2/Bax content of precursor B cells in bone marrow of mice with altered expression of IL 7 and recombinase-activating gene-2. AB - B cell development in mouse bone marrow depends critically upon IL-7. To examine the possible in vivo trophic role of IL-7, we have quantitated apoptosis and Bcl 2 family proteins in populations of phenotypically defined B lineage cells in IL 7-deficient and IL-7-overexpressing mice. Using immunofluorescence labeling, multiparameter flow cytometry, and a short-term culture assay, we show that the apoptotic rates of precursor B cells, but not of more mature B cells, are enhanced by IL-7 gene deletion, associated with increased intracellular content of Bax and decreased Bcl-2, while, conversely, an IL-7 transgene suppresses precursor B cell apoptosis and produces low Bax and high Bcl-2 levels. During normal B cell development, high Bax/Bcl-2 ratios characterize cells undergoing greatest apoptotic cell death. Pro-B cells in RAG-2-/- mice, all destined to abort, show elevated Bax levels and Bax/Bcl-2 ratios. By comparison with the elevated rate of pro-B cell apoptosis in RAG-2-/- mice, provisional estimates have been made for the fraction of pro-B cells undergoing apoptosis in normal mice (70%), IL-7-/- mice (85%), and IL-7 transgenic mice (35%). The results demonstrate that IL-7 strongly promotes in vivo cell survival and maintains antiapoptotic Bcl-2/Bax ratios during the development of precursor B cells in mouse bone marrow. PMID- 9973462 TI - The p65 subunit of NF-kappa B is redundant with p50 during B cell proliferative responses, and is required for germline CH transcription and class switching to IgG3. AB - B cells lacking individual NF-kappa B/Rel family members exhibit defects in activation programs. We generated small resting B cells lacking p65 or p50 alone, or lacking both p50 and p65, then evaluated the ability of these cells to proliferate, secrete Ig, and undergo Ig class switching. B cells lacking p65 proliferated well in response to all stimuli tested. However, these cells demonstrated an isolated defect in switching to IgG3, which was associated with a decrease in gamma 3 germline CH gene expression. Whereas, previously reported, B cells lacking p50 alone had a severe proliferative defect in response to LPS, a moderate defect in response to CD40 ligand (CD40L), and normal proliferation to Ag receptor cross-linking using dextran-conjugated anti-IgD Abs (alpha delta dex), B cells lacking both p50 and p65 exhibited severely impaired proliferation in response to LPS, alpha delta-dex, and CD40L. This defect could be overcome by simultaneous administration of alpha delta-dex and CD40L. In response to this latter combination of stimuli, B cells lacking both p50 and p65 secreted Ig and underwent isotype switching to IgG1 as efficiently as B cells lacking p50 alone. These data demonstrate a role for the p65 subunit of NF-kappa B in germline CH gene expression as well as functional redundancy between p50 and p65 during proliferative responses. PMID- 9973463 TI - The role of CD80, CD86, and CTLA4 in alloimmune responses and the induction of long-term allograft survival. AB - Blocking the interaction of the CD28 costimulatory receptor with its ligands, CD80 and CD86, inhibits in vivo immune responses, such as allograft rejection, and in some instances induces tolerance. Previously, we found that CTLA4Ig, which blocks the CD28/CTLA-4 (CD152) ligands CD80 and CD86, can be used to induce transplantation tolerance to vascularized allografts. Recent data suggest that an intact CD152-negative signaling pathway is essential for induction of tolerance to nominal Ags. Here, we show that blockade of CD152 using an anti-CD152 mAb at the time of transplantation prevents the induction of long-term allograft survival by agents that target CD80 and CD86. In contrast, CD152 signals are not required for the maintenance of established graft survival. We also report for the first time that blockade of CD86 alone can induce long-term graft survival. This requires that anti-CD86 mAb is given on the day of transplantation and also depends upon an intact CD152 pathway. This result, plus experiments using CD80 deficient mice, suggests a dominant role for CD80 molecules on donor cells as the relevant ligand for CD152. We additionally find that blockade of CD152 at the time of transplantation does not interfere with the effectiveness of anti-CD154 mAbs, suggesting distinct mechanisms for inhibition of graft rejection by blocking the CD28 vs CD154 pathways. PMID- 9973464 TI - CD38-mediated signaling events in murine pro-B cells expressing human CD38 with or without its cytoplasmic domain. AB - To elucidate the signaling mechanism of CD38 (a transmembrane molecule highly expressed in immature hemopoietic cells), we transfected Ba/F3 murine pro-B cells with a cDNA encoding human CD38. CD38 ligation with anti-CD38 Abs caused rapid, transient, dose-dependent tyrosine phosphorylation of several proteins, including the tyrosine kinase TEC and the adaptor molecule CBL, and association of tyrosine phosphorylated proteins with phosphatidylinositol 3-kinase p85. Exposure to anti CD38 Abs or their F(ab')2 and Fab also induced tight aggregation of CD38 transfected Ba/F3 cells, which appeared to be Ca2+ and Mg2+ independent and did not involved LFA-1. Aggregation was abrogated by addition of the tyrosine kinase inhibitor herbimycin A and was delayed by the phosphatidylinositol 3-kinase inhibitor wortmannin, suggesting a link between biochemical events and cellular effects induced by CD38. Cell aggregation was accompanied by a decrease in cell recovery. After 3 days of culture on bone marrow-derived stroma, the mean (+/-SD) cell recovery in the presence of anti-CD38 (T16) was 10.5 +/- 9.2% (n = 7) of that in parallel cultures with an isotype-matched nonreactive Ab. Finally, CD38 ligation in Ba/F3 cells expressing a mutant human CD38 lacking the cytoplasmic domain induced tyrosine phosphorylation with intensity and kinetics similar to those seen with the entire protein. It also induced cell aggregation and decreased cell recovery. We conclude that CD38 triggers remarkably similar signaling pathways in human and murine immature B cells. This signaling is independent of the CD38 cytoplasmic domain, suggesting the existence of accessory transmembrane molecules associated with CD38. PMID- 9973465 TI - Lymphotactin acts as an innate mucosal adjuvant. AB - Lymphotactin (Lptn) is a C chemokine produced predominantly by NK and CD8 positive (CD8+) T cells including gammadelta TCR-positive (TCR+) intraepithelial lymphocytes. Lptn is chemotactic for NK and T cells and likely plays an important role in maintaining the integrity of the epithelium and in mucosal immune responses. In this study, we characterized the immune responses to OVA given intranasally with Lptn to mice. This regimen enhanced OVA-specific serum Ab responses and Ab titers in mucosal secretions. Lptn also enhanced OVA-specific Ab forming cells in mucosal and systemic compartments. CD4-positive (CD4+) T cells isolated from mucosal compartments and spleens of mice intranasally immunized with OVA plus Lptn displayed higher OVA-specific proliferative responses and greater synthesis of IFN-gamma, IL-2, IL-4, IL-5, IL-6, and IL-10 than did CD4+ T cells from mice given OVA without Lptn. These studies indicate that Lptn has adjuvant properties and suggest that Lptn present in the mucosa has the potential to enhance mucosal and systemic Ab responses through help provided by Th1- and Th2-type cells to link the initial innate signals of the mucosa with the acquired immune system. PMID- 9973466 TI - Identification of tyrosine phosphorylation sites in the CD28 cytoplasmic domain and their role in the costimulation of Jurkat T cells. AB - The cytoplasmic domain of CD28 contains four tyrosine residues. Because signal transduction by CD28 appears to involve its tyrosine phosphorylation, we determined sites of CD28 tyrosine phosphorylation using mutants of mouse CD28 that retained tyrosine at one position, with the remaining three positions mutated to phenylalanine. When expressed in Jurkat cells and stimulated by mAb, only the mutants with tyrosine at position 170 or 188 were tyrosine phosphorylated. Phosphorylation of Tyr170 recruits phosphatidylinositol 3-kinase to CD28. Tyr188 has not been associated with any specific signaling event, but we found that ligation of CD28 by the natural ligand B7.2 also induced phosphorylation of Tyr188, suggesting that this event is of physiological importance. Consistent with that possibility, mutation of Tyr188 to phenylalanine severely impaired the ability of mouse CD28 to deliver a costimulus for the expression of CD69 and the production of IL-2. The functional consequences of the mutation of Tyr188 were unique; mutation of the other three tyrosines, individually or in combination, did not impair costimulation. Therefore, of the four CD28 tyrosine residues only Tyr188 is required for signaling in Jurkat cells, suggesting that its phosphorylation is a key event in the costimulation of T cells. PMID- 9973467 TI - Dose-dependent induction of distinct anergic phenotypes: multiple levels of T cell anergy. AB - T cell anergy has been proposed as one of the mechanisms underlying peripheral T cell tolerance. In recent years, the functional relevance of T cell anergy has been studied extensively in vitro and in vivo, using different species, cell systems, and ways to induce anergy. Although these studies concurred about the induction of unresponsiveness, conflicting findings were obtained with respect to the function of anergic T cells and to the persistence of T cell anergy. In the present study, T cell anergy was induced through T-T presentation of the specific Ag by rat MHC class II+ T cells in the absence of professional APC. We show that, depending on the Ag dose with which T cells were incubated, distinct anergic phenotypes were induced. Incubation of T cell clones with a low (suboptimal) Ag dose induced hyporesponsiveness. Incubation with a higher (optimal) Ag dose induced an anergic state capable of exerting immunoregulatory effects. Incubation with a high (supraoptimal) Ag dose led to an anergic suppressive phenotype that was persistent and was not reversed by APC, Ag, and rIL-2. These findings demonstrate that T cell anergy is not confined to a single state of functional inactivation. Instead, multiple levels of T cell anergy exist. Thus, anergic T cells can contribute to the regulation of the immune response either in a persistent and active manner or in a passive manner, depending on their level of T cell anergy. PMID- 9973468 TI - Use of antagonist peptides to inhibit in vitro T cell responses to Par j1, the major allergen of Parietaria judaica pollen. AB - Antigenic peptides with substituted side chains inhibit immune responses to a number of recall Ags from infectious agents in vitro. Here we show that the same strategy can be applied to peptides derived from a pollen protein, the major allergen of Parietaria judaica(Par j1), a plant responsible for most allergenic sensitization in the southern Mediterranean area. Three T cell lines responding to Par j1 protein were used to identify a stimulatory peptide. Two different monosubstituted altered peptide ligands (APL) were identified that bound to the HLA-DR of the responders, did not stimulate the T cell lines on their own, and decreased the response to subsaturating amounts of the unmodified stimulatory peptide. Most important, these APL were able to inhibit the response of these cell lines to intact Par j1 protein. A third monosubstituted peptide bound to the HLA-DR but did not show inhibitory activity. The two APL had a lower affinity than the unsubstituted peptide for the HLA-DR. The last two observations make MHC blockade an unlikely explanation for the observed effect. These results indicate the action of a specific peptide-mediated antagonism that may be useful in controlling the T cell component of an allergic response. PMID- 9973469 TI - Fas ligand induction in human NK cells is regulated by redox through a calcineurin-nuclear factors of activated T cell-dependent pathway. AB - Fas ligand (FasL) on cytotoxic lymphocytes is important for mediating apoptosis of activated lymphocytes and other target cells. We have reported that NK cell functions, such as proliferation, cell death, and killing activity, are subject to regulation by cellular redox status. Here, we report that expression of FasL protein and mRNA in activated NK cells is also regulated by redox. Ligation of CD16 on IL-2-preactivated NK cells resulted in reduction of intracellular peroxide level as well as induction of FasL expression. This CD16-induced FasL expression was suppressed by oxidative stress, including thiol deprivation or treatment with hydrogen peroxide (H2O2). Addition of thiol-reducing compounds, such as L-cystine, 2-ME, or N-acetyl cysteine, restored FasL expression. These data suggest that CD16 stimulation requires cellular reducing status for FasL induction in NK cells. Because FasL gene activation following CD16 cross-linking is regulated by the NF of activated T cells (NFAT), we examined the effect of oxidative stresses on NFAT activation. Electrophoretic mobility shift assays revealed that both thiol insufficiency and H2O2 treatment suppressed DNA-binding activity of NFAT and that addition of thiol-reducing compounds reversed or even enhanced it. Furthermore, these oxidative stresses inhibited activity of calcineurin, a serine/threonine phosphatase that regulates NFAT activation. These results suggest that suppression of calcineurin and NFAT activation is a mechanism by which oxidative stress inhibits FasL induction in activated NK cells and further support the hypothesis that thiol-reducing compounds might be required for maintenance of optimal NK functions under physiologic oxidative conditions. PMID- 9973470 TI - Intranasally induced immunological tolerance is determined by characteristics of the draining lymph nodes: studies with OVA and human cartilage gp-39. AB - Mucosal tolerance is a naturally occurring immunological phenomenon that prevents harmful inflammatory responses to ingested or inhaled environmental, predominantly nondangerous, Ags. The nasal mucosa is an extremely efficient compartment in the induction of immunological tolerance which can be exploited in Ag-specific treatment of autoimmune disease. With the use of a model Ag (OVA) and an Ag implicated in the autoimmune disease rheumatoid arthritis (human cartilage gp-39), we here show in a mouse model that the superficial cervical and internal jugular lymph nodes that drain the nasal mucosa are instrumental in the induction of tolerance. Removal of these lymph nodes abrogates tolerance induction, which can be restored by transplantation of superficial cervical lymph nodes, but not of peripheral lymph nodes. The results indicate that lymph nodes that directly drain the nasal mucosa constitute a unique microenvironment which favors the induction of immunological tolerance. PMID- 9973471 TI - Evidence of positive cross-regulation on Th1 by Th2 and antigen-presenting cells: effects on Th1 induced by IL-4 and IL-12. AB - The response of Th cells to cytokines is normally strictly regulated, such that following antigenic stimulation, Th cells respond for only a short period of time, after which they become refractory to cytokine-mediated effects. IL-12, a costimulator of Th1 having no proliferation-inducing capacity of its own, allows Th1 clones and lines to respond to IL-4 when they would otherwise be unable to respond to this cytokine. Cells that have proliferated in response to IL-4 plus IL-12 are fully able to be subsequently activated by specific Ag and APC. Additionally, the response to IL-4 of Th1 effector cells derived from normal murine spleen is enhanced significantly by IL-12. Furthermore, in the presence of IL-12, stimulated Th2 can induce proliferation of Th1 via IL-4 production, in a dual chamber culture system. We hypothesize that the effects of IL-4 and IL-12 represent a novel, positive cross-regulatory pathway that acts on Th1, and is mediated by Th2 (the IL-4 source) and APC (the IL-12 source). We propose this as a way for a Th2 immune response to positively influence an ongoing or waning Th1 response. PMID- 9973472 TI - Dual MHC class I and class II restriction of a single T cell receptor: distinct modes of tolerance induction by two classes of autoantigens. AB - In the final stages of thymic development, immature T cells undergo three distinct processes (positive selection, negative selection, and lineage commitment) that all depend on interactions of thymocyte TCRs with MHC molecules. It is currently thought that TCRs are preferentially restricted by either MHC class I or class II molecules. In this report, we present direct evidence that the TCR previously described as H-Y/H-2Db specific cross-reacts with H-2IAb if expressed in CD4+ cells. We also demonstrate an increase in thymocyte numbers in H-Y TCR-trangenic mice deficient in MHC class II, suggesting a relatively discrete form of negative selection by MHC class II compared with that induced by H-Y/H-2Db. We propose that inability to generate CD4+ T cells expressing H-Y TCR in different experimental settings may be due to tolerance to self-MHC class II. These results, therefore, support an intriguing possibility that tolerance to self may influence and/or interfere with the outcome of the lineage commitment. PMID- 9973473 TI - Specific CD3 epsilon association of a phosphodiesterase 4B isoform determines its selective tyrosine phosphorylation after CD3 ligation. AB - cAMP-specific phosphodiesterases (PDE) comprise an extensive family of enzymes that control intracellular levels of cAMP and thus regulate T cell responses. It is not known how the function of these enzymes is altered by TCR engagement. We have examined this issue by studying one of the PDE isozymes (PDE4B). PDE4B RNA and protein were detected in resting PBLs, and the levels of PDE4B protein increased with cell cycling. In peripheral blood T cells, two previously reported PDE4B isoforms could be detected: one was 75-80 kDa (PDE4B1) and the other was 65 67 kDa (PDE4B2). These two isoforms differed in their N-terminal sequence, with the presence of four potential myristylation sites in the PDE4B2 that are absent in PDE4B1. Consequently, only PDE4B2 was found in association with the CD3var epsilon chain of the TCR. In addition, although both isoforms were phosphorylated in tyrosines in pervanadate-stimulated T cells, only the TCR-associated PDE4B2 was tyrosine-phosphorylated following CD3 ligation. The kinetics of phosphorylation of TCR-associated PDE4B2 correlated with changes in cAMP levels, suggesting that tyrosine phosphorylation of the TCR-associated PDE4B isoform upon engagement of this receptor may be an important regulatory step in PDE4B function. Our results reveal that selectivity of PDE4B activation can be achieved by differential receptor association and phosphorylation of the alternatively spliced forms of this PDE. PMID- 9973474 TI - CD40 activation boosts T cell immunity in vivo by enhancing T cell clonal expansion and delaying peripheral T cell deletion. AB - In this report we show that activation of APC with an agonist anti-CD40 mAb profoundly alters the behavior of CD4 T cells in vivo. Stimulation of mice with anti-CD40 2 days before, but not 1 day after, administration of superantigen (SAg) enhanced CD4 and CD8 T cell clonal expansion by approximately threefold. Further, CD40 activation also delayed peripheral T cell deletion after activation. Dying, activated T cells were quantitated by detecting extracellular phosphatidylserine with concomitant staining for SAg-reactive T cells using a TCR Vbeta-specific mAb. Upon close examination, it was shown that CD40 activation delayed the death of the activated T cells. Additionally, it was found that enhanced survival of CD4 T cells was equally dependent on APC expression of B7-1 and B7-2. This is in contrast to CD8 T cells, which did not depend as much on B7 1 as B7-2. Thus, CD40 activation indirectly promotes T cell growth and delays the death of SAg-stimulated CD4 T cells in vivo. These data suggest that one way CD40 activation promotes a more robust immune response is by indirectly increasing the production of effector T cells and by keeping them alive for longer periods of time. PMID- 9973475 TI - Positive recognition of MHC class I molecules by the Ly49D receptor of murine NK cells. AB - Members of the murine Ly49 family of receptors have been shown to inhibit and activate NK cell function. Subsets of Ly49-expressing NK cells mediate the rejection of bone marrow cell allografts and the lysis of allogeneic lymphoblasts. In this report we have studied Ly49-mediated positive and negative signaling in an in vitro cytotoxicity assay using sorted NK cell subsets as effectors and a panel of 51Cr-labeled Con A lymphoblasts as targets in the presence or the absence of Abs to Ly49 and/or class I molecules. Our results demonstrate that the activating receptor Ly49D delivers stimulatory signals for target cell lysis upon interacting with H2-Dd, Dr, and Dsp2, but not H2b or H2k class I Ags. On the other hand, the inhibitory receptor Ly49G2 delivers negative signals for target cell lysis upon interacting with Dd, Dr, and H2k, but not H2b or Dsp2, class I Ags. Furthermore, Ly49-mediated negative signaling dominates Ly49D-mediated positive signaling. Thus, lysis of class I MHC-bearing targets by NK cells is not merely the consequence of the absence of an Ly49-mediated negative signal, but also requires positive recognition of class I molecules by certain Ly49 receptors. Activation of NK cells by nonself class I molecules was not predicted by the missing self hypothesis. PMID- 9973476 TI - Human effector memory T cells express CD86: a functional role in naive T cell priming. AB - The glycoprotein CD86 expressed on APCs provides a costimulatory signal necessary for an efficient activation of naive T cells. In contrast, there is controversy about the condition of expression and the function of CD86 on T cells. In this study, we have analyzed the phenotype and the biological activity of CD86+ T cells generated from human PBMC. Results show that CD86 expression on T cells is induced by long term stimulation via CD3 and IL-2R and is down-regulated as the cells become quiescent. The CD86-expressing cells are memory effector T cells: 1) they express CD45RO and high levels of the activation markers CD25, CD54, and HLA Dr; 2) they selectively express CD30, CD40-ligand, and CD70; and 3) in response to stimulation, most of them produce IFN-gamma before dying by apoptosis. We then analyzed whether CD86 expressed on T cells is functional. Results show that paraformaldehyde-fixed CD86+ T cells enhance the proliferation and production of IFN-gamma by anti-CD3 mAb-stimulated naive T cells and induce proliferation of resting allogenic T cells. All these effects are prevented by neutralizing anti CD86 mAbs. In contrast, we report no autocrine effect of CD86 in CD86+ T cell activation. In conclusion, these data show that human memory effector T cells express a functional form of CD86 that can costimulate naive T cell responses. PMID- 9973477 TI - Lysophosphatidic acid and sphingosine 1-phosphate protection of T cells from apoptosis in association with suppression of Bax. AB - Members of a subfamily of G protein-coupled receptors (GPCRs), encoded by five different endothelial differentiation genes (edgs), specifically mediate effects of lysophosphatidic acid (LPA) and sphingosine 1-phosphate (S1P) on cellular proliferation and differentiation. Mechanisms of suppression of apoptosis by LPA and S1P were studied in the Tsup-1 cultured line of human T lymphoblastoma cells, which express Edg-2 and Edg-4 GPCRs for LPA and Edg-3 and Edg-5 GPCRs for S1P. At 10-10 M to 10-7 M, both LPA and S1P protected Tsup-1 cells from apoptosis induced by Abs to Fas, CD2, and CD3 plus CD28 in combination. Apoptosis elicited by C6 ceramide was inhibited by S1P, but not by LPA, in part because ceramide suppressed expression of Edg-2 and Edg-4 surface receptors for LPA without affecting Edg-3 surface receptors for S1P. At 10-9 M to 10-7 M, LPA and S1P significantly suppressed cellular levels of the apoptosis-promoting protein Bax, without altering the levels of Bcl-xL or Bcl-2 assessed by Western blots and immunoassays. Transfections of pairs of antisense plasmids for Edg-2 plus Edg-4 and Edg-3 plus Edg-5, and hygromycin selection of transfectants with reduced expression of the respective Edg R proteins in Western blots, inhibited both protection from apoptosis and reduction in cellular levels of Bax by LPA and S1P. Thus, LPA and S1P protection from apoptosis is mediated by distinct Edg GPCRs and may involve novel effects on Bax regulatory protein. PMID- 9973478 TI - Calcium-dependent activation of TNF family gene expression by Ca2+/calmodulin kinase type IV/Gr and calcineurin. AB - CD40 ligand (L), FasL, and TNF-alpha are members of the TNF family of cytokines. All are expressed by T lymphocytes shortly after activation but have distinct effector functions. Transcription of these genes can be induced by stimulation of T cells by calcium ionophore alone and requires the calcineurin-dependent transcription factor NF of activated T cells. We have examined a second calcium dependent signaling pathway, mediated by calcium/calmodulin-dependent kinase IV (CaMKIV) in transcriptional activation of TNF family genes. In reporter gene assays using constructs driven by the promoters of human CD40L, FasL, or TNF alpha along with vectors expressing constitutively active CaMKIV and calcineurin, we have demonstrated that each promoter is activated by calcineurin and CaMKIV in a synergistic fashion. Furthermore, specific inhibition of CaMKIV by chemical means and by a dominant negative mutant of CaMKIV impairs the ionomycin-induced activity of all three promoters as well as protein expression of CD40L and TNF alpha. Our results indicate that activation of gene expression by calcineurin and CaMKIV is common to members of the TNF cytokine family. PMID- 9973479 TI - Beta 1 integrin cross-linking inhibits CD16-induced phospholipase D and secretory phospholipase A2 activity and granule exocytosis in human NK cells: role of phospholipase D in CD16-triggered degranulation. AB - Recent data indicate that integrin-generated signals can modulate different receptor-stimulated cell functions in both a positive (costimulation) and a negative (inhibition) fashion. Here we investigated the ability of beta 1 integrins, namely alpha 4 beta 1 and alpha 5 beta 1 fibronectin receptors, to modulate CD16-triggered phospholipase activation in human NK cells. beta 1 integrin simultaneous cross-linking selectively inhibited CD16-induced phospholipase D (PLD) activation, without affecting either phosphatidylinositol phospholipase C or cytosolic phospholipase A2 (PLA2) enzymatic activity. CD16 induced secretory PLA2 (sPLA2) protein release as well as its enzymatic activity in both cell-associated and soluble forms were also found to be inhibited upon beta 1 integrin coengagement. The similar effects exerted by specific PLD pharmacological inhibitors (2,3-diphosphoglycerate, ethanol) suggest that in our experimental system, sPLA2 secretion and activation are under the control of a PLD-dependent pathway. By using pharmacological inhibitors (2,3 diphosphoglycerate, wortmannin, ethanol) we also demonstrated that PLD activation is an important step in the CD16-triggered signaling cascade that leads to NK cytotoxic granule exocytosis. Consistent with these findings, fibronectin receptor engagement, by either mAbs or natural ligands, resulted in a selective inhibition of CD16-triggered, but not of PMA/ionomycin-induced, degranulation that was reversed by the exogenous addition of purified PLD from Streptomyces chromofuscus. PMID- 9973480 TI - Serial TCR engagement and down-modulation by peptide:MHC molecule ligands: relationship to the quality of individual TCR signaling events. AB - In the present study, we examined the relationships among quantitative aspects of TCR engagement as measured by receptor down-modulation, functional responses, and biochemical signaling events using both mouse and human T cell clones. For T cells from both species, ligands that are more potent in inducing functional responses promote TCR down-modulation more efficiently than weaker ligands. At low ligand density, the number of down-modulated TCR exceeds the number of available ligands by as much as 80-100:1 in the optimal human case, confirming the previous description of serial ligand engagement of TCR (Valitutti, et al. 1995. Nature 375:148-151). A previously unappreciated relationship involving TCR down-modulation, the pattern of proximal TCR signaling, and the extent of serial engagement was revealed by analyzing different ligands for the same TCR. Functionally, more potent ligands induce a higher proportion of fully tyrosine phosphorylated zeta-chains and a greater amount of phosphorylated ZAP-70 than less potent ligands, and the number of TCR down-modulated per available ligand is higher with ligands showing this full agonist-like pattern. The large number of receptors showing partial zeta phosphorylation following exposure to weak ligands indicates that the true extent of TCR engagement and signaling, and thus the amount of sequential engagement, is underestimated by measurement of TCR down modulation alone, which depends on full receptor activation. These data provide new insight into T cell activation by revealing a clear relationship among intrinsic ligand quality, signal amplification by serial engagement, functional T cell responses, and observable TCR clearance from the cell surface. PMID- 9973481 TI - IL-2, but not IL-4 and other cytokines, induces phosphorylation of a 98-kDa protein associated with SHP-2, phosphatidylinositol 3'-kinase, and Grb2. AB - Binding of IL-2 to its receptor activates several biochemical pathways, including JAK-STAT, Ras-mitogen-activated protein kinase, and phosphatidylinositol 3' kinase (PI 3'-kinase) pathways. Recently, it has been shown that the SH2 containing phosphatase, SHP-2, becomes phosphorylated in response to IL-2 stimulation, associates with PI3'-kinase and Grb2, and can exert a positive regulatory role in IL-2 signaling. We now report the identification of a prominent 98-kDa protein (p98) found to be phosphorylated in response to IL-2 stimulation and coprecipitated with SHP-2, the p85 subunit of PI 3'-kinase and Grb2. Interestingly, whereas IL-4 is known to activate PI 3'-kinase, we did not observe any p98 phosphorylation in response to IL-4 stimulation. p98 can form a multipartite complex with all these proteins as immunodepleting with anti-p85 antiserum substantially reduced the amount of p98 immunoprecipitated by SHP-2 and Grb2; the converse was also true. Furthermore, phosphorylation of p98 did not occur in cells lacking JAK3, suggesting that it may be a JAK substrate. Finally, deglycosylation of p98 did not alter its migration, suggesting p98 is not a member of the recently described SHP substrate/signal-regulatory proteins family of transmembrane glycoproteins. Thus p98 is a prominent IL-2-dependent substrate that associates with multiple proteins involved in IL-2 signaling and may play an important role in coupling the different signal transduction pathways activated by IL-2. PMID- 9973482 TI - Mitogen-activated protein kinase activation through Fc epsilon receptor I and stem cell factor receptor is differentially regulated by phosphatidylinositol 3 kinase and calcineurin in mouse bone marrow-derived mast cells. AB - Aggregation of high affinity FcR for IgE (Fc epsilon RI) on mast cells activates intracellular signal transduction pathways, including the activation of protein tyrosine kinases, phosphatidylinositol 3-kinase (PI3-kinase), and protein kinase C. Binding of stem cell factor (SCF) to its receptor (SCFR, c-Kit) on mast cells also induces increases in intrinsic tyrosine kinase activity and activation of PI3-kinase. Although ligation of both receptors induces Ras and Raf-1 activation, the downstream consequences of these early activation events are not well defined, except for the activation of extracellular signal-regulated kinases (ERK). Addition of Ag (OVA) to mouse bone marrow-derived mast cells (BMMC) sensitized with anti-OVA IgE triggers the activation of three members of the mitogen-activated protein (MAP) kinase family, c-Jun amino-terminal kinase (JNK), p38 MAP kinase (p38), and extracellular signal-regulated kinases. SCF similarly activates all three MAP kinases. Wortmannin, an inhibitor of PI3-kinase, inhibited both Fc epsilon RI- and SCFR-mediated JNK activation and partially inhibited Fc epsilon RI, but not SCFR-mediated p38 activation. Cyclosporin A inhibited Fc epsilon RI-mediated JNK and p38 activation, but did not affect the activation of these kinases when stimulated through the SCFR. Wortmannin and cyclosporin A inhibited Fc epsilon RI-mediated production of TNF-alpha and IL-4 in addition to serotonin release in BMMC. These results indicate that both PI3 kinase and calcineurin may contribute to the regulation of cytokine gene transcription and the degranulation response by modulating JNK activity in BMMC. PMID- 9973483 TI - Immunosuppressive leflunomide metabolite (A77 1726) blocks TNF-dependent nuclear factor-kappa B activation and gene expression. AB - Leflunomide is a novel immunosuppressive and antiinflammatory agent currently being tested for treatment of autoimmune diseases and transplant rejection. NF kappa B is a transcription factor activated in response to a wide variety of inflammatory stimuli, including TNF, but whether leflunomide blocks NF-kappa B activation is not known. In the present report we demonstrate that treatment of a human T cell line (Jurkat) with leflunomide blocks TNF-mediated NF-kappa B activation in a dose- and time-dependent manner, with maximum inhibition at 5-10 microM. Inhibition was not restricted to TNF-induced activation, because leflunomide also inhibited NF-kappa B activation induced by other inflammatory agents, including phorbol ester, LPS, H2O2, okadaic acid, and ceramide. Leflunomide blocked the degradation of I kappa B alpha and subsequent nuclear translocation of the p65 subunit, steps essential for NF-kappa B activation. This correlated with inhibition of dual specificity-mitogen-activated protein kinase kinase as well as an Src protein tyrosine kinase, p56lck, by leflunomide. Reducing agents did not reverse the effect of leflunomide. Leflunomide also suppressed the TNF-activated NF-kappa B-dependent reporter gene expression. Our results thus indicate that leflunomide is a potent inhibitor of NF-kappa B activation induced by a wide variety of inflammatory stimuli, and this provides the molecular basis for its anti-inflammatory and immunosuppressive effects. PMID- 9973484 TI - Functional expression of receptors for calcitonin gene-related peptide, calcitonin, and vasoactive intestinal peptide in the human thymus and thymomas from myasthenia gravis patients. AB - The molecular and functional expression of serpentine membrane receptors for vasoactive intestinal peptide (VIP), calcitonin gene-related peptide (CGRP), and calcitonin (CT) were characterized in human thymus and thymomas from myasthenia gravis (MG) patients and thymic epithelial cells either in primary culture (PTEC) or transformed by the simian virus 40 large T (SV40LT) oncogene (LT-TEC). Using RT-PCR combined with Southern analysis, we identified the PCR products corresponding to the receptor (-R) transcripts for VIP, CGRP, and CT in thymus from control subjects and MG patients with either hyperplasia or thymoma. Similar expressions of the VIP- and CGRP-R transcripts were observed in PTEC, whereas the CT-R message was not detected. In LT-TEC, the signals for VIP-R, CGRP-R, and CT-R transcripts were seen with a lower intensity than those in control and MG thymus. In agreement with our molecular analysis, 1) VIP was the most potent peptide among VIP-related peptides (VIP > PACAP > PHM > PHV) to stimulate cAMP production through specific type 1 VIP receptors in both PTEC and LT-TEC; 2) cAMP generation was induced by CGRP in PTEC and by CT in LT-TEC; 3) in frozen thymic sections and by flow cytometry, type 1 VIP-R, CGRP-R, and CT-R were localized in epithelial cells; and 4) in parallel, the transcription of the acetylcholine receptor alpha subunit (the main autoantigen in MG) was induced by CGRP and CT in PTEC and LT TEC, respectively. Our data suggest that the neuroendocrine peptides VIP, CGRP, and CT may exert functional roles during MG and malignant transformation of the human thymus. PMID- 9973485 TI - The orientation and nature of the interaction between beef insulin-specific TCRs and the insulin/class II MHC complex. AB - Recent crystallographic studies suggest that TCR interact with peptide/class I MHC complexes in a single preferred orientation. Although similar studies have not been performed for class II-restricted TCR, it has been proposed that T cell recognition of peptide/class II complexes has similar orientational restrictions. This study represents a functional approach to systematic analysis of this question. Twenty-one mutant A beta(d) molecules were produced by alanine scanning mutagenesis and assessed for their ability to present species variants of insulin to a panel of beef insulin-specific T cell hybridomas with limited TCR alpha- and/or beta-chain sequence differences. We demonstrate that all beef insulin specific TCR have the same orientation on the insulin/Ad complex, such that the alpha-chain interacts with the carboxyl-terminal region of the A beta(d) alpha helix, and the beta-chain complementarity-determining region 3 interacts with the carboxyl-terminal portion of the peptide, consistent with that observed for crystallized TCR-peptide/class I complexes. Despite this structural constraint, even TCR that share structural similarity show remarkable heterogeneity in their responses to the panel of MHC mutants. This variability appears to result from conformational changes induced by binding of the TCR to the complex and the exquisite sensitivity of the threshold for T cell activation. PMID- 9973486 TI - Extensive junctional diversity in Ig light chain genes from early B cell progenitors of mu MT mice. AB - Nontemplated (N) nucleotide additions contribute significantly to the junctional diversity of all Ag receptor chains in adult mice except Ig light (L) chains, primarily because terminal deoxynucleotidyl transferase (TdT) expression is turned off at the time of their rearrangement in pre-B cells. However, because some Ig L chain gene rearrangements are detectable earlier during B cell ontogeny when TdT expression is thought to be maximal, we have examined the junctional processing of kappa- and lambda-chain genes of CD45(B220)+CD43+ pro-B cells from mu MT mice. We found that both kappa and lambda coding junctions formed in these B cell precursors were extensively diversified with N-region additions. Together, these findings demonstrate that Ig L chain genes are equally accessible to TdT in pro-B cells as Ig heavy chain genes. Surprisingly, however, the two L chain isotypes differed in the pattern of N addition, which was more prevalent at the lambda-chain locus. We observed the same diversity pattern in pre-B cells from TdT-transgenic mice. These results suggest that some aspects of TdT processing could be influenced by factors intrinsic to the sequence of Ig genes and/or the process of V(D)J recombination itself. PMID- 9973487 TI - Functional characterization of the somatic hypermutation process leading to antibody D1.3, a high affinity antibody directed against lysozyme. AB - The impact of somatic hypermutation on the affinity of Abs directed against protein Ags remains poorly understood. We chose as a model the secondary response Ab D1.3 directed against hen egg lysozyme. During the maturation process leading to this Ab, five replacement somatic mutations occurred. After reconstituting the germline Ab from which D1.3 originated, we assessed the energetic and kinetic importance of each of the somatic mutations, individually or combined, using the BIAcore apparatus. We found that the mutations induced an overall 60-fold improvement of affinity, principally due to a decrease in the kinetic rate of dissociation. We showed that their effects were additive and context independent; therefore, in the case of D1.3, the order in which somatic mutations were introduced and selected is unimportant. Interestingly, most of the affinity improvement was due to a single somatic mutation (Asn50-->Tyr in VL), involving a residue that belongs to the functional interface between Ab D1.3 and lysozyme. This replacement could either establish new Van der Waals contacts between the Ab and the Ag or help stabilize the conformation of a closely situated crucial residue of the Ab paratope. The four other mutations played only a marginal part in affinity maturation; potential reasons for which these mutations were nevertheless selected are discussed. PMID- 9973488 TI - Molecular mechanisms and selection influence the generation of the human V lambda J lambda repertoire. AB - To define the lambda light chain repertoire in humans, a single-cell PCR technique using genomic DNA obtained from individual peripheral B cells was employed. Of the 30 known functional V lambda genes, 23 were detected in either the nonproductive or productive repertoires. Specific V lambda genes, including 2A2, 2B2, 1G, and 4B, were overexpressed in the nonproductive repertoire, whereas some V lambda genes, such as 3R, 2A2, 2B2, 1C, 1G, and 1B, were overexpressed in the productive repertoire. Comparison of the nonproductive and productive repertoires indicated that no V lambda genes were positively selected, whereas a number of V lambda genes, including 4C, 1G, 5B, and 4B, were negatively regulated. All four of the functional J lambda segments were found in both repertoires, with J lambda 7 observed most often. Evidence of terminal deoxynucleotidyltransferase activity was noted in nearly 80% of nonproductive V lambda J lambda rearrangements, and exonuclease activity was apparent in the majority. Despite this, the mean CDR3 length was 30 base pairs in both productive and nonproductive repertoires, suggesting that it was tightly regulated at the molecular level. These results have provided new insights into the dimensions of the human V lambda repertoire and the influences that shape it. PMID- 9973489 TI - Identification of residues in the first domain of human Fc alpha receptor essential for interaction with IgA. AB - The FcR family contains multiple receptors for Igs, of which the most distantly related ( approximately 20%) is the IgA receptor (human Fc alpha R), being more homologous ( approximately 35%) to another family of killer-inhibitory receptor related immunoreceptors with a 19q13.4 chromosomal location in humans. This study of the Fc alpha R demonstrated that, like several IgG receptors, Fc alpha R is a low affinity receptor for Ab (Ka approximately 106 M-1). Rapid dissociation of the rsFc alpha R:IgA complex (t1/2 approximately 25 s) suggests that monomer IgA would bind transiently to cellular Fc alpha Rs, while IgA immune complexes could bind avidly. Mutagenesis of histidyl 85 and arginyl 82, in the FG loop of domain 1, demonstrated that these residues were essential for the IgA-binding activity of Fc alpha R, while arginyl 87 makes a minor contribution to the binding activity of the receptor. This site is unusual among the Fc receptors (Fc gamma RII, Fc gamma RIII, and Fc epsilon RI), in which the ligand binding site is in domain 2 rather than domain 1, but like Fc alpha R, the FG loop comprises part of the ligand binding site. The putative F and G strands flanking the Fc alpha R ligand binding site are highly homologous in the other killer-inhibitory receptor related immunoreceptors, suggesting they comprise a conserved structural element on which divergent FG loops are presented and participate in the specific ligand interactions of each of these receptors. PMID- 9973490 TI - Increased TNF-alpha-induced apoptosis in lymphocytes from aged humans: changes in TNF-alpha receptor expression and activation of caspases. AB - Aging is characterized by increased T cell lymphopenia, T cell dysfunction, and increased serum TNF levels. In this study, we have examined the role of TNF induced apoptosis in T cell deficiency in lymphocytes from aged humans. The constitutive expression of TNF receptors (TNFRI and TNFRII) and the adapter molecules, including TNFR-associated death domain protein (TRADD), TNFR associated factor 2 (TRAF-2), and receptor interacting protein (RIP), were analyzed both at the protein level by flow cytometry or Western blotting, and at the mRNA level using quantitative PCR or Northern blotting in lymphocytes from aged and young subjects. The susceptibility of T cells to undergo TNF-induced apoptosis was analyzed using terminal deoxynucleotidyltransferase-mediated UTP end-labeling (TUNEL) and DNA ladder assays. Caspase (caspase-8 and caspase-3) activation was compared between aged and young subjects using Western blotting and colorimetric assays. In lymphocytes from aged humans, there was an increased susceptibility of CD4+ and CD8+ T cells to undergo TNF-alpha-induced apoptosis, as observed by TUNEL assay and DNA fragmentation ladder assay. Increased TNF alpha-induced apoptosis was also observed in both CD45RA+ and CD45RO+ T cells from aging subjects. An increased constitutive expression of TNFRI and TRADD and decreased expression of TNFRII and TRAF-2 were observed in lymphocytes from aged as compared with young controls. In addition, there was an early and increased activation of caspases (caspase-8 and caspase-3) involved in TNFR/TNF signaling pathway, as evident by early cleavage of caspase-8, poly(ADP-ribose) polymerase (PARP), and caspase-3 substrate DEVD-p-nitroamilide NA. These data suggest that an increased TNF-alpha-induced apoptosis may play a role in T cell deficiency associated with human aging. PMID- 9973491 TI - Position effects of variable region carbohydrate on the affinity and in vivo behavior of an anti-(1-->6) dextran antibody. AB - IgG is a glycoprotein with an N-linked carbohydrate structure attached to the CH2 domain of each of its heavy chains. In addition, the variable regions of IgG often contain potential N-linked carbohydrate addition sequences that frequently result in the attachment of V region carbohydrate. Nonetheless, the precise role of this V region glycan remains unclear. Studies from our laboratory have shown that a naturally occurring somatic mutant of an anti-dextran Ab that results in a carbohydrate addition site at Asn58 of the VH has carbohydrate in the complementarity-determining region 2 (CDR2) of the VH, and the presence of carbohydrate leads to an increase in affinity. However, carbohydrate attached to nearby positions within CDR2 had variable affects on affinity. In the present work we have extended these studies by adding carbohydrate addition sites close to or within all the CDRs of the same anti-dextran Ab. We find that carbohydrate is attached to all the novel addition sites, but the extent of glycosylation varies with the position of the site. In addition, we find that the position of the variable region carbohydrate influences some functional properties of the Ab, including those usually associated with the V region such as affinity for Ag as well as other characteristics typically attributed to the Fc such as half-life and organ targeting. These studies suggest that modification of variable region glycosylation provides an alternate strategy for manipulating the functional attributes of the Ab molecule and may shed light on how changes in carbohydrate structure affect protein conformation. PMID- 9973492 TI - Context-dependent immunogenicity of an S206G-substituted H-2Db-restricted simian virus 40 large T antigen epitope I variant. AB - SV40 large tumor Ag (Tag) contains four H-2b-restricted (I, II/III, IV, and V) CTL epitopes. A hierarchy exists among these CTL epitopes. CTL directed against epitopes I, II/III, and IV are readily detected following immunization of H-2b mice with SV40, Tag-transformed syngeneic cells, or a vaccinia recombinant that expresses full-length Tag, while epitope V-specific CTL are not. The mechanisms that define this hierarchy remain unknown. Initial studies have shown that the locations of epitopes I and V within SV40 Tag do not determine the immunological potencies of these epitopes. Like the wild-type Tag, derivatives in which the locations of epitopes I and V were precisely reversed within Tag failed to induce epitope V-specific CTL, but did induce epitope I-specific CTL. The use of an S206G-substituted epitope I variant (GAINNYAQKL) revealed that the S206G variant sequence induced CTL when located within the native epitope I context, but failed to do so when located within the epitope V context of Tag. Mutagenesis of residues adjacent to the S206G-substituted epitope I variant revealed that the identity of the residue flanking the amino terminus of the S206G variant was critical when it resided within the epitope V location, but not within the epitope I location. These results demonstrate that effects imposed by both regional context and adjacent residues can modulate immunogenicity, but that the relative importance of such effects varies in an epitope-dependent manner. PMID- 9973493 TI - Molecular basis of human complement C1s deficiency. AB - This is the first report on the molecular basis of human complement C1s deficiency. Two abnormalities in the C1s gene were identified in a Japanese family, including one patient, by using exon-specific PCR, single-strand conformation polymorphism analysis, and nucleotide sequencing. A deletion of 4 bp, TTTG, was identified in exon X when using genomic DNA from the patient, his father, and his paternal grandmother. They were all heterozygous for the mutation. The mutant gene encodes a truncated C1s from the N terminus to the short consensus repeat domain. By further sequencing the PCR products, a nonsense mutation from G to T was identified at codon 608 in exon XII in the patient, his mother, and his sister. They were all heterozygous for the nonsense mutation. The mutant gene encodes a truncated form of C1s that lacks the C-terminal 80 amino acids. These results indicate that the patient was a compound heterozygote with the 4-bp deletion on the paternal allele and the nonsense mutation on the maternal allele. The levels of serum C1s seem to be correlated to the genotypes of the C1s gene in which no C1s was detected in the patient, and one-half of the normal level in the family members who are heterozygous for either mutation. The present study demonstrates that the disease is inherited in an autosomal recessive mode. PMID- 9973494 TI - Two human neonatal IgM antibodies encoded by different variable-region genes bind the same linear peptide: evidence for a stereotyped repertoire of epitope recognition. AB - Two monoclonal IgM Abs have been produced from lymphocytes isolated from two human umbilical cord bloods. These mAbs recognize a conformational epitope present in a CNBr digestion fraction of lactoferrin. Linear epitopes recognized by each mAb were selected from several phage display peptide libraries. In each case, phages displaying a peptide with a motif defined by [WF],G,[EQS],N were recovered. Phages displaying that motif bound equally well to either mAb but did not bind to control IgM. A peptide bearing this motif competed with the phage displayed peptides for binding to either mAb. The same peptide also competes with a component of the CNBr digestion fraction of lactoferrin for Ab binding in ELISA. The Abs use different families of VH, JH, and VK gene cassettes but use the same JK cassette. All segments are virtually identical to their germline gene counterparts. This work provides further evidence that certain innate specificities are stereotyped among individuals. PMID- 9973495 TI - Signal transduction pathways involved in the activation of NF-kappa B, AP-1, and c-fos by Mycoplasma fermentans membrane lipoproteins in macrophages. AB - Mycoplasma fermentans-derived membrane lipoproteins (LAMPf) have been demonstrated to stimulate monocytic cells and to induce the secretion of proinflammatory cytokines by a mechanism involving the triggering of protein tyrosine kinase and mitogen-activated protein kinase cascades. Herein, we have examined the effects of LAMPf on the activation of a series of transcription factors potentially involved in cytokine gene expression. LAMPf was capable of inducing NF-kappa B, activated protein 1 (AP-1), and c-fos activation in macrophages and of stimulating NF-kappa B and AP-1 transactivation. Furthermore, we have delineated the contribution of each mitogen-activated protein kinase pathway to the LAMPf-mediated activation of AP-1, c-fos, and NF-kappa B. Whereas the selective extracellular signal-regulated kinase pathway inhibitor PD-98059 did not affect the LAMPf-mediated transactivation of AP-1, c-fos, or NF-kappa B, the specific p38 inhibitor SB203580 abrogated this activity. A c-Jun N-terminal kinase-dominant negative was shown to block the activation of AP-1 without altering NF-kappa B or c-fos activation by LAMPf. In addition, D609, a selective inhibitor of phosphatidylcholine-specific phospholipase C, was shown to block both translocation and transactivation of either NF-kappa B or AP-1 in response to LAMPf. Although LAMPf-mediated macrophage activation is CD14 independent, we could not distinguish between the intracellular mechanisms leading to the macrophage activation triggered by either LPS or LAMPf. This suggests that macrophages display a common signaling machinery leading to the secretion of proinflammatory cytokines in response to different bacterial products. The comprehension of these mechanisms may help to better understanding the bacterial pathogenesis and to elucidate general mechanisms of macrophage activation leading to cytokine secretion. PMID- 9973496 TI - Mycobacterium bovis bacille Calmette-Guerin enhances pathogenicity of simian immunodeficiency virus infection and accelerates progression to AIDS in macaques: a role of persistent T cell activation in AIDS pathogenesis. AB - It has recently been proposed that Mycobacterium tuberculosis may enhance the pathogenicity of HIV infections and accelerate the course of HIV disease. This hypothesis has been tested in the present study using a simian immunodeficiency virus of macaques (SIVmac)/Mycobacterium bovis bacille Calmette-Guerin (BCG) coinfected macaque model. Naive and chronically SIVmac-infected monkeys were evaluated. Following BCG inoculation, the SIVmac-infected monkeys exhibited the dominant responses of TCR-beta complementarity-determining region 3-restricted T cell subpopulations. This BCG-driven T cell activation correlated with a marked increase in viral loads in SIVmac-infected monkeys. Moreover, the prolonged T cell activation coincided with the enhanced decline of CD4+ PBL counts and the accelerated progression to clinical AIDS in the coinfected monkeys, suggesting that Mycobacterium-driven T cell activation may be the mechanism underlying the enhanced pathogenicity of AIDS virus infection in the coinfected individuals. Within 2 to 7 mo after BCG coinfection, all chronically SIVmac-infected monkeys died from SIV-induced AIDS including tuberculosis-like disease. Surprisingly, the naive monkeys manifested a T cell activation-related toxic shock syndrome and a profound depletion of CD4+ lymphocytes 2 wk after simultaneous SIVmac/BCG inoculation. These naive animals died 2 mo after SIVmac/BCG inoculation, with the evidence of the persistent SIV p27 antigenemia and SIVmac-induced disease. In contrast, the normal monkeys not infected with SIVmac survived BCG infection; the control SIVmac-infected animals showed a natural course of chronic SIV infection. Thus, results from this SIV/BCG coinfection model strongly support the hypothesis that active coinfection with HIV and Mycobacterium can impact remarkably on the AIDS virus-induced disease. PMID- 9973497 TI - IL-12 administered during Chlamydia psittaci lung infection in mice confers immediate and long-term protection and reduces macrophage inflammatory protein-2 level and neutrophil infiltration in lung tissue. AB - Protection against infections with the intracellular bacterium Chlamydia spp. requires Th1-polarized CD4+ T cell immunity. In BALB/c mouse lung infections, immediate innate and nascent Chlamydia-specific immune responses following intranasal inoculation of Chlamydia psittaci strain B577 were modulated by 7-day i.p. administration of murine rIL-12, the initiation cytokine for Th1 immunity. Treatment with IL-12 reduced the severity of chlamydial pneumonia, abolished mortality (37.5% in untreated mice), and significantly reduced numbers of chlamydial organisms in lungs. On day 4 after inoculation, the neutrophil:macrophage ratio in bronchointerstitial pneumonias was 1.96 in untreated mice and 0.51 in IL-12-treated mice. This immediate, IL-12-mediated shift in innate inflammatory phenotype was correlated with a significant reduction of lung concentrations of the neutrophil chemoattractant macrophage inflammatory protein (MIP)-2 (putative murine homologue of human IL-8), monocyte chemotactic protein-1, and TNF-alpha; and a reduction in MIP-1alpha and IFN gamma, at high-dose infection only, and IL-12-independent IL-10 levels. Chlamydia specific Ab titers and Ig isotype ratios indicated an IL-12-dependent Th1 shift. Recall responses of IL-12-primed mice to secondary chlamydial lung infection eliminated chlamydiae more effectively and generated a lung cytokine profile conducive to perpetuation of the Th1 memory population. These data support the hypothesis that genetic differences in endogenous IL-12 production and response pathways could determine disease outcomes characterized by poor chlamydial clearance and a purulent inflammatory infiltrate vs effective elimination of chlamydiae in a macrophage-dominated response. PMID- 9973498 TI - Isolation of high avidity melanoma-reactive CTL from heterogeneous populations using peptide-MHC tetramers. AB - Immunogenic peptides of human tumor Ag have been used to generate antigen specific CTL. However, the vast majority of these peptide-specific CTL clones are of low avidity and are peptide, but not tumor, reactive. Peptide-MHC tetramers have been shown to bind specific TCRs with sufficient affinity to be useful reagents for flow cytometry. In this paper we demonstrate that peptide-MHC tetramers can also be used to selectively identify high avidity tumor-reactive CTL and enrich, from a heterogeneous population, the subpopulation of peptide reactive T cells that can lyse tumor targets. The melanoma proteins, MART-1 and gp100, were used to induce potentially tumor-reactive T cells, and the intensity of T cell staining by TCR binding of specific peptide-MHC tetramers was assessed. A range of fluorescence intensity was detected, and the magnitude of tetramer binding was correlated with T cell avidity. The population of peptide-reactive T cells was phenotypically similar with regard to expression of TCR and adhesion molecules, suggesting that this differential avidity for tumor cells reflected differential affinity of the TCR for its peptide-MHC ligand. Sorting, cloning, and expansion of tetramerhigh CTL from a heterogeneous population of peptide stimulated PBMCs enabled rapid selection of high avidity tumor-reactive CTL clones, which retained their functional and tetramerhigh phenotype on re expansion. These results demonstrate that the avidity of a T cell for its tumor target is due to the specific affinity of the TCR for its peptide-MHC ligand, that this interaction can be described using peptide-MHC tetramers and used to isolate high avidity tumor-reactive CTL. PMID- 9973499 TI - Mitogenic activity of purified capsular polysaccharide A from Bacteroides fragilis: differential stimulatory effect on mouse and rat lymphocytes in vitro. AB - Bacteroides fragilis, a Gram-negative colonic bacterium, induces the formation of abscesses associated with intra-abdominal sepsis in humans. The singular ability of this organism to modulate abscess formation in experimental rodent models resides in the structurally distinct and ionically charged capsular polysaccharides A (PS A) and B (PS B). The regulation of abscess formation in animals is dependent on T lymphocytes. However, the manner in which PS A interacts with T cells remains unknown. We therefore tested the T cell stimulatory capacity of purified PS A on mouse and rat lymphocytes in cellular proliferation assays and found that the PS A molecule possesses mitogenic characteristics distinguishable from those of the polyclonal B cell activator LPS, the T cell mitogen Con A, and staphylococcal enterotoxin A superantigen. Further, PS A stimulated proliferation of normal mouse and rat lymphocytes differentially. Mouse B cells responded to PS A in a fashion that did not require exogenous APC function, while rat T lymphocyte responses to PS A required APC function derived from autologous or xenogenic feeder cells. Cellular depletion experiments showed that the CD4+ subset of rat spleen cells was the primary responder cell type to PS A in vitro. The differential stimulatory effects of PS A on mouse and rat lymphocytes may reflect its ability to stimulate different lymphocyte subsets in vivo through the activities of receptor/counter-receptor pairs present on responder lymphocytes and cognate APC. PMID- 9973500 TI - The role of actin microfilaments in the down-regulation of the degranulation response in RBL-2H3 mast cells. AB - Cross-linking of FcepsilonRI on rat basophilic leukemia (RBL) cells initiates a signaling cascade leading to degranulation of the cells and the release of inflammatory mediators. Inhibitors that disrupt microfilaments, such as latrunculin and cytochalasin D, do not cause any degranulation on their own, but they do enhance FcepsilonRI-mediated degranulation. Dose-response studies show a good correlation between inhibition of actin polymerization and increased degranulation. In RBL cells, latrunculin causes a decrease in basal levels of filamentous actin (F-actin), while cytochalasin D does not. This is particularly evident in the Triton-insoluble pool of F-actin which is highly cross-linked and associated with the plasma membrane. A concentration of 500 nM latrunculin decreases the basal level of Triton-insoluble F-actin by 60-70% and total F-actin levels by 25%. Latrunculin increases both the rate and extent of Ag-induced degranulation while having no effect on pervanadate-induced degranulation. Pervanadate activates the signaling pathways directly and bypasses the cross linking of the receptor. RBL cells, activated through FcepsilonRI in the presence of latrunculin, show increased phospholipase activity as well as increased tyrosine phosphorylation of Syk and increased tyrosine phosphorylation of the receptor itself by the tyrosine kinase Lyn. This indicates that the very earliest signaling events after receptor cross-linking are enhanced. These results suggest that actin microfilaments may interact, either directly or indirectly, with the receptor itself and that they may regulate the signaling process at the level of receptor phosphorylation. Microfilaments may possibly act by uncoupling Lyn from the cross-linked receptor. PMID- 9973501 TI - TCR vaccines against T cell lymphoma: QS-21 and IL-12 adjuvants induce a protective CD8+ T cell response. AB - Tumor-specific TCR can serve as an effective target for active immunotherapy of T cell malignancies. Using the murine T cell tumor model C6VL, vaccination with C6VL TCR protected mice from a subsequent lethal dose of tumor cells. This study characterizes the immune mechanisms involved in the tumor protection, and the influence of immunologic adjuvants in inducing a protective immune response. Immune responses induced by TCR vaccines formulated with various adjuvants: QS 21, IL-12, SAF-1, CD40L, and GM-CSF were compared. QS-21, IL-12, and SAF-1 biased the humoral immune response toward Th1-type, reflected by the induction of IgG2a and IgG2b anti-C6VL TCR Abs. CD40L and GM-CSF exclusively produced IgG1 Abs, reflecting a Th2-type immune response. In our tumor model system, only vaccines containing adjuvants that induced a Th1-type immune response favored tumor protection. Furthermore, we demonstrated that CD8+ T cells were necessary and sufficient for tumor protection using anti-CD8 mAb depletion and adoptive cell transfer experiments. Transfer of hyperimmune serum containing anti-C6VL TCR Abs into na ive mice had modest anti-tumor effects and was not sufficient to prevent tumor growth. TCR-vaccinated B cell-deficient mice were not protected against C6VL tumor, and tumor protection was not completely restored after hyperimmune serum transfer. Thus, B cells may serve as important APCs in inducing a protective immune response. Based on these results future TCR vaccines should be designed to maintain native TCR conformation, as well as induce a strong Th1-type immune response. PMID- 9973502 TI - IFN-gamma-mediated control of Coxiella burnetii survival in monocytes: the role of cell apoptosis and TNF. AB - The treatment of infectious diseases caused by intracellular bacteria, such as Q fever, may benefit from cytokines acting on macrophages. Monocytic THP-1 cells were infected with Coxiella burnetii, the etiological agent of Q fever, and then treated with IFN-gamma. While C. burnetii multiplied in untreated monocytes, IFN gamma reduced bacterial viability after 24 h of treatment and reached maximum inhibition after 96 h. IFN-gamma also affected the viability of infected cells. Cell death resulted from apoptosis; occurring 24 h after the addition of IFN gamma, it reached a maximum after 48 h and was followed by necrosis. Reactive oxygen intermediates were not required for C. burnetii killing, since monocytes from patients with chronic granulomatous disease were microbicidal in response to IFN-gamma. The role of cytokines was also investigated. IFN-gamma elicited a moderate release of IL-1beta in infected monocytes. Moreover, the IL-1 receptor antagonist did not affect C. burnetii survival, suggesting that IL-1beta was not involved in the bacterial killing induced by IFN-gamma. TNF was involved in IFN gamma-induced killing of C. burnetii and cell death. IFN-gamma induced mRNA expression and sustained secretion of TNF. Neutralizing Abs to TNF as well as Abs directed against TNF receptors I and II, significantly prevented IFN-gamma dependent killing of C. burnetii and cell death. These results suggest that IFN gamma promotes the killing of C. burnetii in monocytes through an apoptotic mechanism mediated in part by TNF. PMID- 9973503 TI - Fc gamma receptor-mediated activation of phospholipase D regulates macrophage phagocytosis of IgG-opsonized particles. AB - Receptors for the Fc portion of IgG (Fc gamma Rs) integrate the innate and acquired components of immunity by coupling the specific recognition of IgG Abs to the activation of phagocytic leukocytes. Knowledge of the molecular mechanisms that regulate phagocyte stimulation by Fc gamma Rs may permit therapeutic modulation to augment immunoprotective aspects and minimize damage to host tissues in diverse inflammatory diseases. Since phospholipase D (PLD) has been linked to the stimulation of cytotoxic leukocyte responses, we characterized Fc gamma R-dependent activation of PLD in human macrophages. IgG-coated SRBCs (EIgG) stimulated a 9.4-fold increase in PLD activity compared with SRBCs treated with control Ab (p < 0. 001), determined by formation of the PLD-specific product phosphatidylethanol in the presence of 0.5% ethanol. Levels of phosphatidic acid, the physiologic product of PLD-mediated catalysis, were significantly increased in the absence of ethanol (6.4-fold, p < 0.001). PLD activity was also stimulated by immune complex-coated latex beads or cross-linking of Abs specific for Fc gamma RI, Fc gamma RII, or Fc gamma RIII. Phagocytosis of EIgG was reduced by two inhibitors of PLD-mediated signaling, 2,3-diphosphoglycerate or 1-butanol. Addition of purified PLD restored control levels of phagocytosis in cells in which endogenous PLD was inhibited. The tyrosine kinase inhibitors genistein and herbimycin A caused concordant reductions in Fc gamma R-stimulated PLD activity and phagocytosis. These studies demonstrate that Fc gamma R-mediated phagocytosis is accompanied by tyrosine kinase-dependent activation of PLD and support the hypothesis that stimulation of PLD functions to regulate the ingestion of IgG opsonized particles. PMID- 9973504 TI - Expression of the neutrophil chemokine KC in the colon of mice with enterocolitis and by intestinal epithelial cell lines: effects of flora and proinflammatory cytokines. AB - IL-10 plays an important role in preventing excessive inflammation to the normal flora in the intestinal lumen. The purpose of this study was to compare the effect of normal flora on inflammation in mice in which the IL-10 gene was disrupted. IL-10 knock-out mice housed in germfree conditions remained healthy while those housed in conventional conditions developed colitis after weaning, suggesting that IL-10 inhibits the adverse responses to luminal Ag. Crypt abscesses were present in virtually all of the diseased animals as evidenced by flattening of the epithelial cells and a large number of neutrophils in the lumen of the crypt. Since KC is a chemokine that is capable of recruiting neutrophils in mice, mRNA and protein for KC was measured. Increased levels of both KC mRNA and protein were detected in the colon of diseased mice. To determine whether the epithelial cells were capable of synthesizing KC and contributing to neutrophil accumulation in the crypts, a murine intestinal epithelial cell line (Mode-K) was shown to express mRNA and protein for KC. Two cytokines induced in association with colitis in these mice, TNF-alpha and IFN-gamma, increased the expression of KC mRNA and protein in murine epithelial cells. However, IL-10 was incapable of decreasing the induction of KC, even though the cells expressed the IL-10 receptor. These results suggest that the neutrophil chemokine KC is produced by gastrointestinal epithelial cells in response to inflammatory mediators that are expressed following exposure to normal flora in animals lacking IL-10. PMID- 9973505 TI - The beta-glucan-binding lectin site of mouse CR3 (CD11b/CD18) and its function in generating a primed state of the receptor that mediates cytotoxic activation in response to iC3b-opsonized target cells. AB - Mouse leukocyte CR3 (Mac-1, alphaMbeta2 integrin) was shown to function as a receptor for beta-glucans in the same way as human CR3. Soluble zymosan polysaccharide (SZP) or pure beta-glucans labeled with FITC or 125I bound in a saturable and reversible manner to neutrophils, macrophages, and NK cells. This lectin activity was blocked by anti-CD11b mAb M1/70 or 5C6 and did not occur with leukocytes from CR3-/- (CD11b-deficient) mice. SZP preparations containing primarily mannose or glucose bound to CR3, and the binding of 125I-labeled beta glucan to CR3 was competitively inhibited by beta-glucans from barley or seaweed, but not by yeast alpha-mannan. Also, as with human CR3, the lectin site of mouse CR3 was inhibited by alpha- or beta-methylglucoside (but not D-glucose), alpha- or beta-methylmannoside, and N-acetyl-D-glucosamine. Phagocytosis of zymosan and serum-opsonized zymosan was partially inhibited by anti-CR3 and was reduced to <40% of normal with leukocytes from CR3-/- mice. As with neutrophils from patients with CD18 deficiency, neutrophils from CR3-/- mice exhibited no phagocytosis of particulate beta-glucan. SZP or beta-glucans primed CR3 of neutrophils, macrophages, and NK cells for cytotoxicity of iC3b-opsonized tumor cells that otherwise did not trigger killing. beta-Glucan priming for cytotoxicity was inhibited by anti-CR3 and did not occur with leukocytes from CR3 /- mice. The primed state of macrophage and NK cell CR3 remained detectable for 18 to 24 h after pulsing with beta-glucans. The similarity of mouse and human CR3 in response to beta-glucans highlights the utility of mouse tumor models for development of therapeutic beta-glucans. PMID- 9973506 TI - Bacterial DNA containing CpG motifs stimulates lymphocyte-dependent protection of mice against lethal infection with intracellular bacteria. AB - Bacterial DNA containing unmethylated CpG motifs activates mammalian lymphocytes and macrophages to produce cytokines and polyclonal Ig. These include IFN-gamma, IL-12, TNF-alpha, and IL-6, which are important in the control of intracellular bacterial infection. Here, we show that bacterial DNA, as well as synthetic oligonucleotides containing CpG motifs, induce protection against large lethal doses of Francisella tularensis live vaccine strain (LVS) and Listeria monocytogenes. Methylation of DNA at CpG dinucleotides or inversion of the motif abolished this protection. Surprisingly, DNA-mediated protection was highly dependent on lymphocytes, particularly B cells, as well as the production of IFN gamma. Optimal protection was elicited 2-3 days after inoculation with DNA and persisted for up to 2 wk. Further, animals surviving lethal challenge developed pathogen-specific secondary immunity. These findings indicate that host innate immune responses to bacterial DNA may contribute to the induction of protective immunity to bacteria and the subsequent development of memory. PMID- 9973507 TI - Bacterial superantigens induce down-modulation of CC chemokine responsiveness in human monocytes via an alternative chemokine ligand-independent mechanism. AB - Staphylococcal superantigens (SAgs) are very potent T cell mitogens, but they can also activate monocytes by binding directly to MHC class II molecules in a manner independent of TCR coengagement. Induction of proinflammatory cytokines and chemokine expression in monocytes by superantigens has recently been reported. Here we report that superantigen stimulation of human peripheral blood monocytes results in a rapid, dose-dependent, and specific down-regulation of chemokine (macrophage inflammatory protein-1alpha (MIP-1alpha), monocyte chemotactic protein-1 and MIP-1beta) binding sites (e.g., CCR1, CCR2, and CCR5), which correlates with a concomitant hyporesponsiveness of human monocytes to these CC chemokine ligands. This down-regulation occurs 15-30 min following superantigen stimulation and is specific to chemokine receptors, in that binding and responsiveness of monocytes to the chemoattractant formyl-tripeptide FMLP are not affected. We further demonstrate that SAg-induced down-modulation of chemokine binding and monocyte hyporesponsiveness to the chemokines MIP-1alpha, monocyte chemotactic protein-1, and MIP-1beta is mediated through cellular protein tyrosine kinases, and the down-modulation can be mimicked by an MHC class II specific mAb. Additionally, our observations indicate that SAg-induced loss of chemokine binding and monocyte responsiveness is probably mediated by secreted serine proteinases. Bacterial SAg-induced down-modulation of chemokine responsiveness represents a previously unrecognized strategy by some bacteria to subvert immune responses by affecting the intricate balance between chemokine and chemokine receptor expression and function. PMID- 9973508 TI - Conserved CTL epitopes shared between HIV-infected human long-term survivors and chimpanzees. AB - Certain HIV-1 infected humans that do not progress to AIDS have been documented to share particular MHC class I alleles that appear to correlate with long-term survival. HIV-1-infected chimpanzees are relatively resistant to progression to AIDS. Out of a group of 10 chimpanzees with CTL activity and nonprogressive HIV-1 infection, 2 animals with prominent cytolytic CD3+CD8+ T cell responses to HIV-1 Ags were studied in detail. Characterization of these CTL revealed that they contained the granzymes A and B, T cell intracellular Ag-1, and perforin and induced calcium-dependent cytolysis that correlated with the presence of apoptotic nuclei in target cells. These CTL responses were directed against two gagpeptides, which were found to be identical to previously described epitopes recognized in the context of HLA-B27 and HLA-B57 molecules. The latter two restriction elements occur with increased frequency in human long-term survivor cohorts. Phylogenetic comparisons revealed that the chimpanzee restriction elements, Patr-B*02and -B*03, described here do not show any obvious similarity with the HLA-B*27 and -B*57 alleles, suggesting that CTL responses to HIV-1 in distinct primate species may be controlled by different types of HLA-B-like molecules. The CTL responses in these two chimpanzees are directed, however, against highly conserved epitopes mapping across the majority of HIV-1 clades. PMID- 9973509 TI - Anti-KS: identification of autoantibodies to asparaginyl-transfer RNA synthetase associated with interstitial lung disease. AB - Autoantibodies to five of the aminoacyl-transfer RNA (tRNA) synthetases have been described, and each is associated with a syndrome of inflammatory myopathy with interstitial lung disease (ILD) and arthritis. Serum KS, from a patient with ILD and inflammatory arthritis without evidence of myositis, immunoprecipitated a tRNA that was distinct from that precipitated by any described anti-synthetase or other reported tRNA-related Abs, along with a protein of 65 kDa. KS serum and IgG fraction each showed significant (88%) inhibition of asparaginyl-tRNA synthetase (AsnRS) activity, but not of any of the other 19 aminoacyl-tRNA synthetase activities. Among 884 patients with connective tissue diseases tested, only two other sera were found to immunoprecipitate tRNAs and proteins of identical gel mobility. These two and KS showed identical immunodiffusion lines using HeLa cell extract. The new sera significantly inhibited AsnRS without significant effects on other synthetases tested. Both patients had ILD but neither had evidence of myositis. These data strongly suggest that these three sera have autoantibodies to AsnRS, representing a sixth anti-synthetase. Anti-KS was more closely associated with ILD than with myositis. Further study of this Abs might prove useful in dissecting the stimuli responsible for the genesis of anti-synthetase autoantibodies. PMID- 9973510 TI - In vitro and in vivo dependency of chemokine generation on C5a and TNF-alpha. AB - Under a variety of conditions, alveolar macrophages can generate early response cytokines (TNF-alpha, IL-1), complement components, and chemotactic cytokines (chemokines). In the current studies, we determined the requirements for TNF alpha and the complement activation product C5a in chemokine production in vitro and in vivo. Two rat CXC chemokines (macrophage inflammatory protein (MIP)-2 and cytokine-induced neutrophil chemoattractant (CINC)) as well as three rat CC chemokines (MIP-1alpha, MIP-1beta, and monocyte chemoattractant protein (MCP)-1) were investigated. Chemokine generation in vitro was studied in rat alveolar macrophages stimulated with IgG immune complexes in the absence or presence of Abs to TNF-alpha or C5a. The rat lung injury model induced by IgG immune complex deposition was employed for in vivo studies. Abs to TNF-alpha or C5a were administered intratracheally or i.v., and effects on chemokine levels in bronchoalveolar lavage fluids were quantitated by ELISA. Both in vitro and in vivo studies demonstrated the requirements for TNF-alpha and C5a for full generation of CXC and CC chemokines. In vitro and in vivo blockade of TNF-alpha or C5a resulted in significantly reduced production of chemokines. Supernatant fluids from in vitro-stimulated macrophages revealed by Western blot analysis the presence of C5a/C5adesArg, indicating intrinsic generation of C5a/C5adesArg by alveolar macrophages and explaining the higher efficiency of intratracheal vs i.v. blockade of C5a in reducing chemokine production. These results underscore the central role of both TNF-alpha and C5a, which appear to function as autocrine activators to promote CXC and CC chemokine generation by alveolar macrophages. PMID- 9973511 TI - CD95 (Fas/Apo-1) as a receptor governing astrocyte apoptotic or inflammatory responses: a key role in brain inflammation? AB - Astrocytes are a major cellular component of the brain that are capable of intense proliferation and metabolic activity during diverse inflammatory brain diseases (such as multiple sclerosis, Alzheimer's dementia, tumor, HIV encephalitis, or prion disease). In this biological process, called reactive gliosis, astrocyte apoptosis is frequently observed and could be an important mechanism of regulation. However, the factors responsible for apoptosis in human astrocytes are poorly defined. Here, we report that short term cultured astrocytes derived from different brain regions express significant levels of CD95 at their surface. Only late passage astrocytes are sensitive to CD95 ligation using either CD95 mAb or recombinant CD95 ligand. Blocking experiments using caspase inhibitors with different specificities (DEVD-CHO, z-VAD-fmk, and YVAD-cmk), an enzymatic activity assay, and immunoblotting show that CPP32/caspase-3 play a prominent role in CD95-induced astrocyte death. In contrast, early passage astrocytes are totally resistant to death, but a significant increase in astrocytic IL-8 secretion (p < 0.001, by Wilcoxon's test for paired samples) is observed after CD95 triggering. Production of IL-8 contributes to the resistance of astrocytes to CD95 ligation. Furthermore, in the presence of IFN-gamma, resistant astrocytes became sensitive to CD95-mediated death. These data suggest that microenvironmental factors can influence the consequences of CD95 ligation on astrocytes. Therefore, we propose that CD95 expressed by human astrocytes plays a pivotal role in the regulation of astrocyte life and death and may be a key factor in inflammatory processes in the brain, such as reactive gliosis. PMID- 9973512 TI - Phosphorylation of cytosolic phospholipase A2 and the release of arachidonic acid in human neutrophils. AB - Kinases mediating phosphorylation and activation of cytosolic phospholipase A2 (cPLA2) in intact cells remain to be fully characterized. Platelet-activating factor stimulation of human neutrophils increases cPLA2 phosphorylation. This increase is inhibited by PD 98059, a mitogen-activated protein (MAP)/extracellular signal-regulating kinase (erk) 1 inhibitor, but not by SB 203580, a p38 MAP kinase inhibitor, indicating that this action is mediated through activation of the p42 MAP kinase (erk2). However, platelet-activating factor-induced arachidonic acid release is inhibited by both PD 98059 and SB 203580. Stimulation by TNF-alpha increases cPLA2 phosphorylation, which is inhibited by SB 203580, but not PD 98059, suggesting a role for p38 MAP kinase. LPS increases cPLA2 phosphorylation and arachidonic acid release. However, neither of these actions is inhibited by either PD 98059 or SB 203580. PMA increases cPLA2 phosphorylation. This action is inhibited by PD 98059 but not SB 203580. Finally, FMLP increases cPLA2 phosphorylation and arachidonic acid release. Interestingly, while the FMLP-induced phosphorylation of cPLA2 is not affected by the inhibitors of the p38 MAP kinase or erk cascades, both inhibitors significantly decrease arachidonic acid release stimulated by FMLP. SB 203580 or PD 98059 has no inhibitory effects on the activity of coenzyme A-independent transacylase. PMID- 9973513 TI - Expression and function of the chemokine receptors CXCR1 and CXCR2 in sepsis. AB - Neutrophils (polymorphonuclear neutrophils; PMN) and a redundant system of chemotactic cytokines (chemokines) have been implicated in the pathogenesis of the acute respiratory distress syndrome in patients with sepsis. PMN express two cell surface receptors for the CXC chemokines, CXCR1 and CXCR2. We investigated the expression and function of these receptors in patients with severe sepsis. Compared with normal donors, CXCR2 surface expression was down-regulated by 50% on PMN from septic patients (p < 0.005), while CXCR1 expression persisted. In vitro migratory responses to the CXCR1 ligand, IL-8, were similar in PMN from septic patients and normal donors. By contrast, the migratory response to the CXCR2 ligands, epithelial cell-derived neutrophil activator (ENA-78) and the growth-related oncogene proteins, was markedly suppressed in PMN from septic patients (p < 0.05). Ab specific for CXCR1 blocked in vitro migration of PMN from septic patients to IL-8 (p < 0.05), but not to FMLP. Thus, functionally significant down-regulation of CXCR2 occurs on PMN in septic patients. We conclude that in a complex milieu of multiple CXC chemokines, CXCR1 functions as the single dominant CXC chemokine receptor in patients with sepsis. These observations offer a potential strategy for attenuating adverse inflammation in sepsis while preserving host defenses mediated by bacteria-derived peptides such as FMLP. PMID- 9973514 TI - Neutrophil recruitment by human IL-17 via C-X-C chemokine release in the airways. AB - IL-17 is a recently discovered cytokine that can be released from activated human CD4+ T lymphocytes. This study assessed the proinflammatory effects of human (h) IL-17 in the airways. In vitro, hIL-17 increased the release of IL-8 in human bronchial epithelial and venous endothelial cells, in a time- and concentration dependent fashion. This effect of hIL-17 was inhibited by cotreatment with an anti-hIL-17 Ab and was potentiated by hTNF-alpha. In addition, hIL-17 increased the expression of hIL-8 mRNA in bronchial epithelial cells. Conditioned medium from hIL-17-treated bronchial epithelial cells increased human neutrophil migration in vitro. This effect was blocked by an anti-hIL-8 Ab. In vivo, intratracheal instillation of hIL-17 selectively recruited neutrophils into rat airways. This recruitment of neutrophils into the airways was inhibited by an anti-hIL-17 Ab and accompanied by increased levels of rat macrophage inflammatory protein-2 (rMIP-2) in bronchoalveolar lavage (BAL) fluid. The BAL neutrophilia was also blocked by an anti-rMIP-2 Ab. The effect of hIL-17 on the release of hIL 8 and rMIP-2 was also inhibited by glucocorticoids, in vitro and in vivo, respectively. These data demonstrate that hIL-17 can specifically and selectively recruit neutrophils into the airways via the release of C-X-C chemokines from bronchial epithelial cells and suggest a novel mechanism linking the activation of T-lymphocytes to recruitment of neutrophils into the airways. PMID- 9973515 TI - Anti-ICAM-1 monoclonal antibody R6.5 (Enlimomab) promotes activation of neutrophils in whole blood. AB - R6.5 (BIRR-1, Enlimomab), a murine IgG2a mAb to the human ICAM-1, inhibits leukocyte adhesion to the vascular endothelium, thereby decreasing leukocyte extravasation and inflammatory tissue injury. In initial clinical trials, R6.5 proved to be beneficial in reducing both disease activity in refractory rheumatoid arthritis and the incidence of acute rejection after kidney and liver allograft transplantations. However, adverse effects such as fever, leukopenia, or cutaneous reactions were not infrequent. We studied the effects of R6.5 on neutrophil function in whole blood samples ex vivo. Surprisingly, at the concentrations achieved in clinical trials, R6. 5 activated neutrophilic granulocytes, as indicated by a significant increase in expression of the adhesion molecule beta2-integrin CD11b, a concurrent decrease in L-selectin expression, and an enhancement of the oxidative burst activity. Neutrophil activation was not exerted by an anti-ICAM-1 mAb of the IgG1 isotype, by isotype matched, irrelevant anti-2-phenyloxazolone mAb, or by F(ab')2 fragments of R6.5. Neutrophil activation was completely inhibited by soluble complement receptor type 1. We conclude that in whole blood, R6.5 activates resting neutrophils in a complement-dependent manner. This finding can explain, at least in part, the side effects associated with R6.5 therapy. PMID- 9973516 TI - Vasoactive intestinal peptide and pituitary adenylate cyclase-activating polypeptide inhibit endotoxin-induced TNF-alpha production by macrophages: in vitro and in vivo studies. AB - Vasoactive intestinal peptide (VIP) is a neuropeptide synthesized by immune cells that can modulate several immune aspects, including the function of cells involved in the inflammatory response, such as macrophages and monocytes. The production and release of cytokines by activated phagocytes are important events in the pathogenesis of ischemia-reperfusion injury. There is abundant evidence that the proinflammatory cytokine TNF-alpha is an important mediator of shock and organ failure complicating Gram-negative sepsis. VIP has been shown to attenuate the deleterious consequences of this pathologic phenomenon. In this study we have investigated the effects of VIP and the structurally related neuropeptide pituitary adenylate cyclase-activating polypeptide (PACAP38) on the production of TNF-alpha by endotoxin-activated murine peritoneal macrophages. Both neuropeptides rapidly and specifically inhibit the LPS-stimulated production of TNF-alpha, exerting their action through the binding to VPAC1 receptor and the subsequent activation of the adenylate cyclase system. VIP and PACAP regulate the production of TNF-alpha at a transcriptional level. In vitro results were correlated with an inhibition of both TNF-alpha expression and release in endotoxemic mice in vivo. The immunomodulatory role of VIP in vivo is supported by the up-regulation of VIP release in serum and peritoneal fluid by LPS and proinflammatory cytokines such as TNF-alpha, IL-1beta, and IL-6. These findings support the idea that under toxicity conditions associated with high LPS doses, VIP and PACAP could act as protective mediators that regulate the excessive release of TNF-alpha to reduce inflammation or shock. PMID- 9973517 TI - Immunostimulatory CpG-oligodeoxynucleotides cause extramedullary murine hemopoiesis. AB - Bacterial DNA and the synthetic CpG-oligodeoxynucleotides (ODNs) derived thereof have attracted attention because they activate cells of the adaptive immune system (lymphocytes) and the innate immune system (APCs) in a sequence-dependent manner. Here, we addressed whether CpG-ODNs affect hemopoiesis. Challenging mice with immunostimulatory CpG-ODN sequences led to transient splenomegaly, with a maximum increase of spleen weight at day 6. The induction of splenomegaly by CpG ODNs was sequence-specific, dose-dependent, and associated with an increase in splenic cell count, in numbers of granulocyte-macrophage CFUs (GM-CFUs), and early erythroid progenitors (burst-forming units-erythroid). The transfer of spleen cells from CpG-ODN-pretreated animals into lethally irradiated syngeneic mice yielded an increase of spleen CFUs. Furthermore, the challenge of sublethally irradiated mice with CpG-ODNs caused radioprotective effects, in that recovery of GM-CFUs and cytotoxic T cell function was enhanced. The increase in GM-CFU and CTL function correlated with an enhanced resistance to Listeria infection in irradiated mice. We conclude from these data that CpG-ODNs trigger extramedullary hemopoiesis, and that this finding could be of therapeutic relevance in myelosuppression. PMID- 9973518 TI - Modulation of airway inflammation by passive transfer of allergen-specific Th1 and Th2 cells in a mouse model of asthma. AB - Although evidence is strong that Th cells play a major role in mediating the airway inflammation observed in asthma, the relative contributions of the Th cell subsets, Th1 and Th2, are unclear. It has been suggested that asthma is driven by Th2 predominant responses in the lung, but other data suggest a role for Th1 cells as well. Here we show by intracellular cytokine staining and flow cytometric analysis that in the murine model of OVA-induced airway inflammation, both Th1 and Th2 cells are recruited to the airways. Th1 cells predominate early in the response and Th2 cells predominate late. We further show that increasing the number of Th1 cells by passive transfer of OVA-specific Th1 cells results in increased inflammation. This effect is observed regardless of whether the T cells are transferred before sensitization or after airway inflammation is already in progress. Transfer of Th1 cells also results in increased recruitment of host T cells of both Th1 and Th2 phenotypes. Passive transfer of Th2 cells results in little change in the inflammatory response. These results demonstrate that Ag specific Th1 cells are not protective in this model of asthma, but rather may potentiate the inflammatory response. PMID- 9973519 TI - Determinant spreading associated with demyelination in a nonhuman primate model of multiple sclerosis. AB - Definition of the immune process that causes demyelination in multiple sclerosis is essential to determine the feasibility of Ag-directed immunotherapy. Using the nonhuman primate, Callithrix jacchus jacchus (common marmoset), we show that immunization with myelin basic protein and proteolipid protein determinants results in clinical disease with significant demyelination. Demyelination was associated with spreading to myelin oligodendrocyte glycoprotein (MOG) determinants that generated anti-MOG serum Abs and Ig deposition in central nervous system white matter lesions. These data associate intermolecular "determinant spreading" with clinical autoimmune disease in primates and raise important issues for the pathogenesis and treatment of multiple sclerosis. PMID- 9973520 TI - Cross-linking of CD44 on rheumatoid synovial cells up-regulates VCAM-1. AB - CD44 is a ubiquitous molecule also known as hyaluronic acid or homing receptor. However, the cellular functions and its role in inflammation, for example, rheumatoid synovitis, are currently unknown. In this study, we propose a novel function for CD44. Using synovial cells from rheumatoid arthritis (RA) patients, we demonstrated that CD44 cross-linking and binding to hyaluronan augmented VCAM 1 expression and subsequently VCAM-1-mediated cell adhesion. Briefly, we found that 1) rheumatoid synovial cells highly expressed CD44; 2) cross-linking of CD44 markedly but transiently augmented VCAM-1 expression and its mRNA transcription much more than did IL-1beta and TNF-alpha; 3) hyaluronan, especially when fragmented, also up-regulated VCAM-1; 4) CD44 activated the transcription factor AP-1; and 5) the integrin-dependent adhesive function of RA synovial cells to T cells was also amplified by CD44 cross-linking. These results indicate that the adhesion of RA synovial cells to matrices such as hyaluronic acid through CD44 could up-regulate VCAM-1 expression and VCAM-1-mediated adhesion to T cells, which might in turn cause activation of T cells and synovial cells in RA synovitis. We therefore propose that such cross-talking among distinct adhesion molecules may be involved in the pathogenesis of inflammation, including RA synovitis. PMID- 9973521 TI - IFN-alpha 2B enhances Th1 cytokine responses in bladder cancer patients receiving Mycobacterium bovis bacillus Calmette-Guerin immunotherapy. AB - Combination therapy with intravesical bacillus Calmette-Guerin (BCG) plus IFN alpha for superficial bladder cancer has been demonstrated to be more effective than either single agent alone in animal studies and of suggested greater efficacy in clinical studies. However, the mechanism by which IFN-alpha enhances BCG-mediated antitumor activity is poorly understood. Using PBMCs from bladder cancer patients, IFN-alpha was found to substantially enhance the efficacy of BCG to induce IFN-gamma production. Among 34 patients tested, 80% showed >4-fold increase. This effect of IFN-alpha was observed in both initial and memory responses to BCG. In addition, IFN-alpha up-regulated BCG-induced IL-12 and TNF alpha and down-regulated BCG-induced IL-10. Neutralizing endogenous IL-10 or adding exogenous IL-12 provided further synergy for IFN-gamma production. In clinical practice, intravesical IFN-alpha 2B (50 million units (MU)/dose) was observed to accelerate urinary IFN-gamma production to low-dose BCG (one-tenth or one-third of a full dose) in patients treated with combination therapy compared with BCG alone. These results suggest that IFN-alpha is a potent BCG enhancer that polarizes the BCG-induced immune response toward the cellular immune pathway by promoting Th1 cytokine expression and reducing Th2 cytokine expression. This study provides an immunological basis for future rational use of IFN-alpha in conjunction with intravesical BCG for bladder cancer immunotherapy. PMID- 9973522 TI - "Allergen engineering": variants of the timothy grass pollen allergen Phl p 5b with reduced IgE-binding capacity but conserved T cell reactivity. AB - One problem of conventional allergen-specific immunotherapy is the risk of anaphylactic reactions. A new approach to make immunotherapy safer and more efficient might be the application of engineered allergens with reduced IgE binding capacity but retained T cell reactivity. Using overlapping dodeca peptides, the dominant T cell epitopes of the timothy grass pollen allergen Phl p 5b were identified. By site-directed mutagenesis outside these regions, point and deletion mutants were generated. Allergen variants were analyzed for IgE-binding capacity with sera of different grass pollen allergic patients by Western blotting, Dot blotting, and EAST inhibition test, and for histamine releasing capacity with peripheral blood basophils from different patients. The deletion mutants revealed significantly reduced IgE reactivity and histamine releasing capacity, compared with the wild-type Phl p 5b. Furthermore, in vivo skin prick tests showed that the deletion mutants had a significantly lower potency to induce cutaneous reactions than the wild-type Phl p 5b. On the other hand, T cell clones and T cell lines from different allergic patients showed comparable proliferation after stimulation with allergen variants and wild-type Phl p 5b. Considering their reduced anaphylactogenic potential together with their conserved T cell reactivity, the engineered allergens could be important tools for efficient and safe allergen-specific immunotherapy. PMID- 9973523 TI - Genetic dissection of SLE pathogenesis: adoptive transfer of Sle1 mediates the loss of tolerance by bone marrow-derived B cells. AB - Sle1 is a potent autoimmune susceptibility locus on chromosome 1 originally identified in a genome scan of testcross progeny between the systemic lupus erythematosus-prone NZM2410 strain and C57BL/6. We subsequently produced B6.NZMc1, a congenic strain carrying the NZM2410-derived Sle1 genomic interval on the B6 background and demonstrated that Sle1 mediated the loss of tolerance to chromatin in both the B and T cell compartments. In this communication, we show by adoptive transfer experiments that the autoimmune phenotypes of Sle1 are completely reconstituted in B6 radiation chimeras receiving B6.NZMc1 bone marrow but not by the reciprocal reconstitution, demonstrating that Sle1 is functionally expressed in B cells. In additional experiments, cotransfer of mixtures of bone marrow derived from B6.NZMc1 and nonautoimmune congenic B6 mice carrying allelic T and B cell markers showed that only B cells derived from B6.NZMc1 bone marrow produced anti-chromatin autoantibodies. In contrast, increased expression of CD69 was equivalent in CD4+ T cells derived from either B6.NZMc1 or congenic B6 bone marrow, suggesting that either T cell population could be activated subsequent to loss of tolerance in the B cell compartment. These findings indicate that the expression of Sle1 in B cells is essential for the development of autoimmunity. PMID- 9973524 TI - A conformation-dependent epitope in Addison's disease and other endocrinological autoimmune diseases maps to a carboxyl-terminal functional domain of human steroid 21-hydroxylase. AB - Idiopathic Addison's disease develops as a consequence of autoimmune destruction of steroid-producing cells in the adrenal gland. A major autoantigen is 21 hydroxylase (21OH; P450c21), which is involved in the biosynthesis of cortisol and aldosterone in the adrenal cortex. We selected a number of functionally important 21OH amino acid substitutions, found in patients with congenital adrenal hyperplasia, to study their effects on the binding of 21OH autoantibodies (21OHAb) to 21OH. The ability of 21OHAb to bind in vitro transcribed and translated wild-type 21OH and five different 21OH mutant proteins was quantified by liquid-phase assays. Sera from 21OHAb-positive patients with idiopathic Addison's disease (n = 24), Graves' disease (n = 3), and insulin-dependent diabetes mellitus (n = 1) were used. While the P105L, delE196, and G291S mutations had no effect on autoantibody binding, the P453S mutation had a considerable effect, and the R483P mutation almost completely abolished binding. Synthetic peptides corresponding to linear epitopes defined by amino acids 447 461 and 477-491 were unable to compete with wild-type 21OH for binding to autoantibodies. Direct 21OH DNA sequencing could not reveal any specific genetic variation in alleles found in 21OHAb-positive patients. We conclude that the region involving R483 plays a key role in the formation of a three-dimensional epitope in a functionally important C-terminal domain of the enzyme. PMID- 9973525 TI - Extracellular HIV-1 tat protein up-regulates the expression of surface CXC chemokine receptor 4 in resting CD4+ T cells. AB - Here we report that synthetic HIV-1 Tat protein, immobilized on a solid substrate, up-regulates the surface expression of the CXC-chemokine receptor 4 (CXCR4), but not of the CC-chemokine receptor 5 in purified populations of primary resting CD4+ T cells. The Tat-mediated increase of CXCR4 occurred in a well-defined range of concentrations (1-10 nM of immobilized Tat) and time period (4-8 h postincubation). Moreover, the increase of CXCR4 was accompanied by an increased entry of the HXB2 T cell line-tropic (X4-tropic), but not of the BaL macrophage-tropic strain of HIV-1. The ability of Tat to up-regulate CXCR4 expression was abrogated by the protein synthesis inhibitor cycloheximide, clearly indicating the requirement of de novo synthesis. As Tat protein is actively released by HIV-1 infected cells, our data indicate a potentially important role for extracellular Tat in rendering bystander CD4+ T cells more susceptible to infection with X4-tropic HIV-1 isolates. PMID- 9973526 TI - Adjuvanticity of the cholera toxin A1-based gene fusion protein, CTA1-DD, is critically dependent on the ADP-ribosyltransferase and Ig-binding activity. AB - The ADP-ribosylating enterotoxins, cholera toxin (CT) and Escherichia coli heat labile toxin, are among the most powerful immunogens and adjuvants yet described. An innate problem, however, is their strong toxic effects, largely due to their promiscuous binding to all nucleated cells via their B subunits. Notwithstanding this, their exceptional immunomodulating ability is attracting increasing attention for use in systemic and mucosal vaccines. Whereas others have separated adjuvanticity from toxicity by disrupting the enzymatic activity of the A1 subunit by site-directed mutagenesis, we have constructed a nontoxic molecule that combines the full enzymatic activity of the A1 subunit with a B cell targeting moiety in a gene fusion protein, the CTA1-DD adjuvant. Despite its more selective binding properties, we found comparable adjuvant effects of the novel CTA1-DD adjuvant to that of CT. Here we unequivocally demonstrate, using a panel of mutant CTA1-DD molecules, that the immunomodulating ability of CTA1-DD is dependent on both an intact enzymatic activity and the Ig-binding ability of the DD dimer. Both agents, CT and CTA1-DD, ADP-ribosylate intact B cells. However, contrary to CT, no increase in intracellular cyclic AMP in the targeted cells was detected, suggesting that cyclic AMP may not be important for adjuvanticity. Most remarkably, CTA1-DD achieves similar immunomodulating effects to CT using a ganglioside-GM1 receptor-independent pathway for internalization. PMID- 9973527 TI - Expression of the IL-12 receptor beta 1 and beta 2 subunits in human tuberculosis. AB - To determine whether the Th1 response in tuberculosis correlated with IL-12R expression, we measured expression of the IL-12R beta 1 and IL-12R beta 2 subunits, as well as IL-12R beta 2 mRNA expression in tuberculosis patients and healthy tuberculin reactors. In tuberculosis patients, IFN-gamma production by Mycobacterium tuberculosis-stimulated PBMC was reduced, the percentages of T cells expressing IL-12R beta 1 and IL-12R beta 2 were significantly decreased, and IL-12R beta 2 mRNA expression was also markedly reduced. In contrast, in pleural fluid and lymph nodes at the site of disease in tuberculosis patients, in which IFN-gamma production is enhanced, IL-12R beta 2 mRNA expression was also increased. In M. tuberculosis-stimulated peripheral blood T cells from tuberculosis patients, anti-IL-10 and anti-TGF-beta enhanced IL-12R beta 1 and IL 12R beta 2 expression, and IFN-gamma production. In M. tuberculosis-stimulated peripheral blood T cells from healthy tuberculin reactors, recombinant IL-10 and TGF-beta reduced IL-12R beta 1 and IL-12R beta 2 expression, as well as IFN-gamma production. In combination with prior studies showing increased production of TGF beta by blood monocytes from tuberculosis patients, this suggests that increased TGF-beta production is the underlying abnormality that reduces IL-12R beta 1 and IL-12R beta 2 expression in tuberculosis. Our findings provide evidence that IL 12R expression correlates well with IFN-gamma production in human tuberculosis, and that expression of IL-12R beta 1 and IL-12R beta 2 may play a central role in mediating a protective Th1 response. PMID- 9973528 TI - A novel 22q11.2 microdeletion in DiGeorge syndrome. PMID- 9973529 TI - Activation of Vav and Ras through the nerve growth factor and B cell receptors by different kinases. AB - Engagement of the B-cell antigen receptor (BCR) or the nerve growth factor receptor (NGFR/TrkA) induces activation of multiple tyrosine kinases, resulting in phosphorylation of numerous intracellular substrates. We show that addition of NGF or anti-IgM antibody leads to the early tyrosine phosphorylation of p95(vav), which is expressed exclusively in hematopoietic cells; NGF, similar to crosslinking the BCR, also results in the rapid activation of Ras. The phosphorylation of Vav and activation of Ras triggered by NGF is mediated through Trk tyrosine kinase, whereas signaling through the BCR uses a different tyrosine kinase. We also show that NGF induces tyrosine phosphorylation of Shc and its association with Grb2. Vav and Ras with the adaptor proteins Shc and Grb2 appear to serve as a link between different receptor-mediated signaling pathways and, in human B cells, may play an important regulatory role in neuroimmune interactions. PMID- 9973530 TI - The CD8beta ectodomain contributes to the augmented coreceptor function of CD8alphabeta heterodimers relative to CD8alphaalpha homodimers. AB - Within the lymphoid compartment, CD8 is expressed either as an alphaalpha homodimer or as an alphabeta heterodimer. Prior functional characterization of CD8alpha transfectants has demonstrated that CD8alphaalpha homodimers can reconstitute T cell responses in the absence of the CD8beta subunit. In order to now examine the role of CD8beta in TCR recognition, the CD8alpha cDNA alone or in combination with CD8beta cDNA was transfected into the mouse T cell hybridoma, N15wt, specific for VSV8/Kb. Comparison of antigen-induced IL-2 production reveals that CD8alphabeta+ transfectants are 100-fold more sensitive in molar terms of peptide than CD8alphaalpha+ transfectants. This enhancement of IL-2 production is independent of CD8alpha or CD8beta cytoplasmic tails as demonstrated by analysis of cytoplasmic deletion mutants CD8alpha'beta, CD8alphabeta', and CD8alpha'beta'. These results indicate that the ectodomain of the CD8beta chain greatly enhances the coreceptor function of the CD8alphabeta molecule, at least for certain class I MHC restricted alphabeta TCRs. PMID- 9973531 TI - IgG subclass switching is associated with the severity of experimental autoimmune encephalomyelitis induced with myelin oligodendrocyte glycoprotein peptide in NOD mice. AB - We have recently shown that a single dose of the myelin oligodendrocyte glycoprotein (MOG) peptide 35-55 produces a relapsing-remitting demyelinating disease similar to multiple sclerosis (MS) in Lewis rats. In this study we have assessed the possibility that a subclass of anti-MOG35-55 antibodies influences the clinical outcome of these diseases by examining the classes and isotypes of anti-MOG35-55 antibody produced during the course of MOG35-55-induced demyelinating disease in NOD mice. Following immunization, 7 of the 21 injected mice had only mild diseases, while the 14 others had severe progressive and/or relapsing-remitting diseases. There were no differences in anti-MOG35-55 IgG, IgA, IgM, IgG1, IgG2a, and IgG3 antibody titers between the severe and mild symptoms groups. High levels of IgG2b antibody to MOG35-55 were detected in all mice with severe symptoms. In contrast, none of the mice which contracted a mild disease produced anti-MOG35-55 IgG2b. These results suggest that in NOD mice, the IgG2b antibody response to MOG35-55 is associated with the severity of this MS like demyelinating disease. PMID- 9973532 TI - The cytoplasmic and the transmembrane domains are not sufficient for class I MHC signal transduction. AB - Class I MHC molecules deliver activation signals to T cells. To analyze the role of the cytoplasmic and the transmembrane (TM) domains of class I MHC molecules in T cell activation, Jurkat cells were transfected with genes for truncated class I MHC molecules which had only four intracytoplasmic amino acids and no potential phosphorylation sites or native molecules or both. Cross-linking either the native or the truncated molecules induced IL-2 production even under limiting stimulation conditions of low engagement of the stimulating mAb. Moreover, direct comparison of transfected truncated and native class I MHC molecules expressed on the same cell revealed significant stimulation induced by cross-linking the truncated molecules, despite low expression. In addition, truncated class I MHC molecules were as able to synergize with CD3, CD2, or CD28 initiated IL-2 production as native molecules. In further experiments, hybrid constructs made of the extracellular portion of the murine CD8 alpha chain and of the TM and the intracytoplasmic domains of H-2Kk class I MHC molecule were transfected into Jurkat T cells. The expression of the transfected hybrid molecules was comparable to that of the native HLA-B7 molecules. Cross-linking the intact monomorphic HLA A,B,C epitope or the polymorphic HLA-B7 epitope induced IL-2 production upon costimulation with PMA. In contrast, cross-linking the hybrid molecules generated neither an increase in intracellular calcium concentration ([Ca2+]i) nor stimulated IL-2 production. By contrast, cross-linking intact murine class I MHC molecules induced [Ca2+]i, signal and IL-2 production in transfected Jurkat cells. The data therefore indicate that unlike many other signaling molecules, signaling via class I MHC molecules does not involve the cytoplasmic and the TM portions of the molecule, but rather class I MHC signal transduction is likely to be mediated by the extracellular domain of the molecule. PMID- 9973533 TI - Mycobacterium avium complex activates nuclear factor kappaB via induction of inflammatory cytokines. AB - A variety of microorganisms has been reported to directly induce NF-kappaB, a critical step in the regulation of genes involved in the cellular immune response. In this study, we demonstrate that proinflammatory cytokines such as tumor necrosis factor alpha (TNFalpha) produced upon activation by the Mycobacterium avium complex (MAC) preceed NF-kappaB activity in U937, a human monocytoid cell line. MAC induction of TNFalpha mRNA expression was detected within 15 min after MAC infection, whereas enhanced NF-kappaB binding activity was not detected until 90 to 120 min postinfection. Supershift analysis revealed increased p50 in the MAC-induced NF-kappaB binding complexes. Consistent with an autocrine mechanism, anti-TNFalpha antibody and dexamethasone, a known cytokine inhibitor, both completely suppressed the effect of MAC on the induction of NF kappaB. Taken together, these findings suggest that exposure of monocyte cell membranes to MAC induces endogenous TNFalpha, which in turn enhances NF-kappaB binding activity. The rapid induction of TNFalpha may be important in the initial host response to MAC infection. PMID- 9973534 TI - Effects of in utero alcohol exposure on B cell development in neonatal spleen and bone marrow. AB - The effects of in utero alcohol exposure on neonatal lymphopoiesis were examined in a murine model of fetal alcohol syndrome. At birth, both immature and mature B cells were decreased in the spleens of neonatal animals and these subpopulations of B cells did not recover to normal levels until 3-4 weeks of life. Pre-B cells and total B cells were decreased as well in the bone marrow of ethanol-exposed animals. By 3-4 weeks of life, the number of B cells in the bone marrow recovered to normal levels, but the pre-B cells remained below normal levels through 5 weeks of age. Furthermore, a recently described early B cell progenitor was reduced in frequency in ethanol-exposed neonates. Together, these data suggest that in utero exposure to ethanol can result in abnormalities in B cell development that may initiate at an early stage of B cell development. PMID- 9973535 TI - Aging increases CD8 T cell apoptosis induced by hyperstimulation but decreases apoptosis induced by agonist withdrawal in mice. AB - Apoptosis of T cells is thought to play a critical role in intrathymic T cell selection, in controlling the strength of the immune response to antigens, and in peripheral modulation of the T cell repertoire by influencing memory cell formation and survival. Peripheral T lymphocyte apoptosis or activation-induced cell death can be induced in vitro by repeated stimulation through the T cell receptor (TCR), and several groups have reported that aging increases the susceptibility of T cells to hyperstimulation-induced cell death in mice and humans. Alternately, apoptosis can also be induced in T cells by withdrawal of TCR stimulation from T cell blasts late in the activation process. This agonist withdrawal cell death, unlike apoptosis induced by repeated stimulation, is Fas- and TNFalpha-independent but is modulated by CD30 ligation. We show here that aging leads to an increase in susceptibility to apoptosis induced by repeated stimulation, but also to a decline in mouse CD8 T cell sensitivity to apoptosis induced by agonist withdrawal. Cell mixture experiments show that intercellular signals are required for the induction of apoptosis after agonist withdrawal and that the CD8 cells from aged mice can respond to these death-inducing signals but cannot produce them. A defect in this form of apoptosis after cessation of TCR signaling might contribute to the accumulation of functionally ineffective CD8 cells in aging mice. PMID- 9973536 TI - Cloning thymic precursor cells: demonstration that individual pro-T1 cells have dual T-NK potential and individual pro-T2 cells have dual alphabeta-gammadelta T cell potential. AB - Thymic progenitors have the capacity to generate alphabeta T cells, gammadelta T cells, and NK cells. To determine whether these three lineages derive from a single precursor cell or from different precursors, a procedure was developed for cloning precursor cells from mouse embryonic thymus. The progeny of each pro-T cell clone were then tested for the potential to generate alphabeta, gammadelta, and NK cells. Of these precursor clones, about half displayed dual potential, developing into either T cells or NK cells, demonstrating the existence of a common T/NK precursor cell in the thymus. The other half of the clones were restricted to T cell development. No precursor clones were restricted to NK development. The common T/NK precursors were shown to be of the pro-T1 (CD25(-)) stage whereas the T-restricted precursors were shown to be of the later pro-T2 (CD25(+)) stage. Both alphabeta and gammadelta T cells were generated from all clones derived from either pro-T1 or -T2 precursors. This shows that commitment of a cell to the alphabeta versus gammadelta lineages does not precede rearrangement of the TCR genes (which occurs immediately after the pro-T2 stage). PMID- 9973537 TI - Inhibition of NK cells by murine CMV-encoded class I MHC homologue m144. AB - Murine cytomegalovirus (CMV)-encoded protein m144 is homologous to class I MHC heavy-chain and is thought to regulate NK-cell-mediated immune responses in vivo. To examine the effects of m144 on NK cytotoxicity in vitro, various cell lines were transfected with wild-type m144 or a chimeric construct in which the cytoplasmic domain of m144 was replaced with green fluorescence protein. Burkitt lymphoma line Raji expressed a significant level of m144 as determined by anti m144 mAb binding or the green fluorescence of the fusion protein. The level of m144 expression was relatively low compared with that of transfected murine class I MHC Dd. However, m144 on Raji cells partially inhibited antibody-dependent cell mediated cytotoxicity of IL-2-activated NK cells. NK cells from the CMV susceptible BALB/c as well as those from the resistant C57BL/6 mice were inhibited by m144. Antibodies against the known murine NK inhibitory receptors Ly 49A, C, G, and I did not affect the inhibitory effect of m144. These results suggest that the murine CMV class I MHC homologue m144 partially inhibits NK cells by interacting with a novel inhibitory receptor. PMID- 9973538 TI - Immunodetection of lymphocyte subpopulations involved in allograft rejection in a teleost, Dicentrarchus labrax (L.). AB - Monoclonal antibodies which recognize antigenic determinants expressed by T-cells and Ig-bearing cells, respectively, allowed lymphocyte subpopulations involved in allograft rejection of muscle transplants to be identified in the teleost fish Dicentrarchus labrax (L.). The monoclonal antibody DLT15 first allowed recognizing T-cells involved in an in vivo antigen-driven cellular response in teleosts. Immunohistochemical studies showed a high density of lymphocytes in allografts and provided evidence of predominance of T-cells. The heterogeneity of the cell populations recognized by the antibodies was evidenced by the different size, cytology, and staining patterns of T-cells and Ig-bearing cells. PMID- 9973539 TI - Antagonistic effects of an alternative splice variant of human IL-4, IL-4delta2, on IL-4 activities in human monocytes and B cells. AB - IL-4 is a pleiotropic cytokine which exerts its actions on various lineages of hematopoietic and nonhematopoietic cells. This cytokine is one of the central regulators of immunity in health and disease states. An alternative splice variant, in which the second of four exons is omitted, has been recently described and designated as IL-4delta2. The variant has been previously described as a potential naturally occurring antagonist of human IL-4 (hIL-4)-stimulated T cell proliferation. In this study, we investigated the effects of recombinant human (rh) IL-4delta2 on monocytes and B cells. In monocytes, rhIL-4delta2 blocked inhibitory action of hIL-4 on LPS-induced cyclooxygenase-2 expression and subsequent prostaglandin E2 secretion. In B cells, rhIL-4delta2 was an antagonist of the hIL-4-induced synthesis of IgE and expression of CD23. Our results broaden the spectrum of hIL-4-antagonistic activities of rhIL-4delta2, thus creating the background for the potential use of rhIL-4delta2 as a therapeutic anti-hIL-4 agent. PMID- 9973541 TI - The role of folate transport and metabolism in neural tube defect risk. AB - Neural tube defects (NTDs) are common congenital malformations in humans. While etiologically heterogeneous, for the most part they are multifactorial in their pathogenesis, having both genetic and environmental factors contributing to their development. In recent years, there has been a great deal of epidemiologic evidence demonstrating that women who received multivitamins containing folic acid periconceptionally had significantly reduced occurrence and recurrence risks for producing infants with such malformations. Unfortunately, the mechanism(s) underlying the beneficial effects of folic acid is not well understood. In this article, we review the fundamental embryological processes involved in closing the neural tube, the relevant epidemiologic data on folic acid supplementation and relative NTD risk, as well as several recent studies of candidate genes for NTD sensitivity that are involved in folate transport and metabolism. PMID- 9973542 TI - Blood levels of ammonia and nitrogen scavenging amino acids in patients with inherited hyperammonemia. AB - Plasma levels of glutamine (456 determinations), alanine (434 determinations), and asparagine (431 determinations) and corresponding ammonia levels (260 determinations) were retrospectively analyzed in 30 patients with hyperammonemia secondary to urea cycle disorders (including 3 patients with amino acid transport defects) and 5 patients with propionic acidemia (PA). All patients had elevated glutamine levels on one or more testing except for 2 patients with severe PA and 1 patient with a mild urea cycle disorder. All but 4 patients with urea cycle disorders showed a maximal glutamine level higher than 100 micromol/dl, and 3 patients had a maximal glutamine level of higher than 200 micromol/dl. The only exceptions were 2 asymptomatic ornithine transcarbamylase (OTC)-deficient females, 1 male with mild OTC deficiency, and 1 patient with citrullinemia (CIT) whose plasma glutamine levels were never above 100 micromol/L. Patients with CIT and argininosuccinic aciduria (ASA) showed statistically significant lower levels of glutamine than patients with other urea cycle disorders. However, the maximal glutamine level did not directly correlate with severity of the disorder and within disorders correlated inversely with severity of outcome. Patients with PA showed statistically significant lower glutamine, alanine, and asparagine levels than patients with urea cycle disorders and the severity of this disorder correlated inversely with plasma glutamine levels. Plasma ammonia levels showed a positive correlation with glutamine in patients with carbamyl phosphate synthetase I and OTC deficiency and a negative correlation in patients with PA. Although, most patients also showed elevated levels of alanine and asparagine, their levels generally did not show a good correlation with glutamine (R2 = 0.25 and 0.34, respectively). PMID- 9973543 TI - Differential effects of biotin deficiency and replenishment on rat liver pyruvate and propionyl-CoA carboxylases and on their mRNAs. AB - Although the role of vitamins as prosthetic groups of enzymes is well known, their participation in the regulation of their genetic expression has been much less explored. We studied the effect of biotin on the genetic expression of rat liver mitochondrial carboxylases: pyruvate carboxylase (PC), propionyl-CoA carboxylase (PCC), and 3-methylcrotonyl-CoA carboxylase (MCC). Rats were made biotin-deficient and were sacrificed after 8 to 10 weeks, when deficiency manifestations began to appear. At this time, hepatic PCC activity was 20% of the control values or lower, and there was an abnormally high urinary excretion of 3 hydroxyisovaleric acid, a marker of biotin deficiency. Biotin was added to deficient primary cultured hepatocytes. It took at least 24 h after the addition of biotin for PCC to achieve control activity and biotinylation levels, whereas PC became active and fully biotinylated in the first hour. The enzyme's mass was assessed in liver homogenates from biotin-deficient rats and incubated with biotin to convert the apocarboxylases into holocarboylases, which were detected by streptavidin blots. The amount of PC was minimally affected by biotin deficiency, whereas that of the alpha subunits of PCC and of MCC decreased substantially in deficient livers, which likely explains the reactivation and rebiotinylation results. The expression of PC and alphaPCC was studied at the mRNA level by Northern blots and RT/PCR; no significant changes were observed in the deficient livers. These results suggest that biotin regulates the expression of the catabolic carboxylases (PCC and MCC), that this regulation occurs after the posttranscriptional level, and that pyruvate carboxylase, a key enzyme for gluconeogenesis, Krebs cycle anaplerosis, and fatty acid synthesis, is spared of this control. PMID- 9973544 TI - The benzoquinone ansamycin geldanamycin stimulates proteolytic degradation of focal adhesion kinase. AB - FAK is a nonreceptor tyrosine kinase involved in adhesion-mediated signal transduction whose level of expression is related to the invasiveness of malignant tumors. In seeking strategies to downregulate FAK, we treated various cell lines in vitro with the benzoquinone ansamycin geldanamycin (GA) which was previously described as a tyrosine kinase inhibitor, but recently has been shown to exert its effects by interfering with the chaperone function of members of the hsp90 family of heat-shock proteins. We evaluated the effects of benzoquinone ansamycins on FAK steady-state protein level and FAK half-life in breast and prostate carcinoma, Ewing's sarcoma, and 3T3 fibroblasts. Our data demonstrate that GA stimulates the proteolytic degradation of FAK in all cell lines examined and markedly reduces the half-life of newly synthesized FAK protein without significantly altering the level of FAK mRNA. These data demonstrate FAK to be another tyrosine kinase sensitive to the destabilizing effects of benzoquinone ansamycins and further show that small molecule-mediated pharmacologic modulation of FAK protein level is a feasible approach to the interdiction of FAK function. PMID- 9973545 TI - Expression patterns of folate binding proteins one and two in the developing mouse embryo. AB - Expression patterns of mRNAs coding for the murine folate binding proteins one and two (FBP1 and FBP2) were determined by ribonuclease protection assay (RPA) in highly inbred SWV/Fnn mouse embryos. Tissue samples for RPA were collected from the anterior neural tube throughout the period of embryonic development, as well as from maternal- and fetal-derived term placenta. The peak in expression of FBP1 occurred in term placental tissue compared to neural tissue from any time point. This relative increase in FBP1 expression occurred in placental tissue of embryonic, as opposed to maternal, origin. The expression of FBP2 did not differ statistically between any timepoints or tissues examined. Expression of both FBP1 and FBP2 was slightly elevated throughout the period of neural tube closure (Gestational Days 8 through 10), although not significantly. These data fit the anticipated expression patterns of the homologues of human folate receptors alpha and beta, thus helping to resolve some of the confusion secondary to the nomenclature associated with this gene family. Furthermore, the expression of these two genes in the neural tube closure stage of embryological development supports their involvement in regulatory events related to normal neural tube morphogenesis. PMID- 9973546 TI - Sensitivity of synthetic surfactants to albumin inhibition in preterm rabbits. AB - Surfactant can be inhibited in vivo by plasma proteins invading the alveolar space during acute lung injury. The resistance to protein inhibition of surfactant preparations with various synthetic surfactant proteins B and C (B and C) was tested in preterm rabbits. Surfactants consisted of a palmitic acid containing phospholipid mixture (PL) with full-length SP-B peptide (B1-78), one of two SP-B mutants (Bserine and BR236C), the synthetic SP-B mimic KL4 (UCLA KL4), a natural SP-B (Bbovine), synthetic palmitoylated SP-C peptide (C1-35), a combination of B1-78 + C1-35, a combination of BR236C + C1-35, and the clinical surfactant Survanta. Preterm rabbits born at 28 days of gestation were ventilated and received 100 mg/kg of albumin intratracheally at 30 min and 100 mg/kg of surfactant at 45 min after birth. Dynamic lung compliance (tidal volume/mean airway pressure) decreased from 0.82 to 0.57 mL/kg/cm H2O after albumin instillation and to 0.43 mL/kg/cm H2O over a 60-min period after saline placebo. Treatment with B1-78 + C1-35 and BR236C + C1-35 surfactant and Survanta returned dynamic compliance to prealbumin values, B1-78, BR236C, Bbovine, and C1-35 surfactant stabilized dynamic compliance, but PL, Bserine, and UCLA-KL4 surfactant were unable to prevent a further deterioration in dynamic compliance. These data suggest that a combination of synthetic surfactant peptides B1-78 and C1-35 and the clinical surfactant Survanta confer a high degree of resistance to surfactant inhibition by human albumin in ventilated preterm rabbits. PMID- 9973547 TI - Activity of IMP- and AMP-preferring isoforms of 5'-nucleotidase from human seminal plasma with AMP analogues. AB - AMP analogues modified at various positions of the molecule were checked as substrates for the two soluble isoforms of 5'-nucleotidase from human seminal plasma. These isoforms were isolated to near homogeneity by affinity chromatographies. AMP derivatives were differently dephosphorylated by both the isoforms depending on the site of modification in the natural compound. Changes in the phosphate moiety reduced significantly hydrolysis by the IMP-preferring form, whereas the AMP-preferring form was less affected. The AMP-preferring form was characterized by a relatively broad specificity toward substrate analogues indicating that the binding domains for the phosphate moiety of these isoforms are not identical. Substitutions at the C-8 adenine base reduced the hydrolysis rate of both the enzymes and variations of the syn-anti conformational equilibrium resulted in different effects on catalysis by both forms. Therefore, the orientation of the heterocyclic base around the glycosidic bond may not be the crucial factor affecting binding and catalytic activity. Hydrogen bonding potential of base N-7 was essential for the binding and catalysis of the IMP- but not of the AMP-preferring form. This was the most striking difference between the studied isoforms. Modifications and substitutions of 6-amino function, better accepted by the IMP-preferring form than by the AMP-preferring form, indicated that no essential hydrogen bonding is required for catalytic activity. The binding was however significantly slowed in 6-SH-PuMP. Hydrogen bonding potential of N-1 was significant for the hydrolysis rate of the IMP- but not of the AMP preferring form. We suggest that these human seminal plasma isoforms of soluble 5'-nucleotidase, characterized by unique features, may represent the tissue specific expression of the polymorphic gene. PMID- 9973548 TI - Effects of Ca2+ on erythrocyte membrane skeleton-bound phosphofructokinase, ATP levels, and hemolysis. AB - Erythrocyte Ca2+ overload is known to occur in several different disease states, and to affect the erythrocyte membrane deformability. We show here that an increase in intracellular Ca2+ concentration in erythrocytes, induced by ionomycin, caused a reduction in ATP levels. Concomitant to the fall in ATP, a marked activation of phosphofructokinase (PFK) (EC 2.7.1.11), the rate-limiting enzyme in glycolysis, in the membrane skeleton fraction occurred. The increase in the membrane skeleton-bound PFK activity was most probably mediated by Ca2+, as direct addition of Ca2+ to the membrane skeleton fraction from the erythrocyte induced an enhancement of the bound PFK activity. Time-response curves revealed that erythrocyte hemolysis did not occur during the first 30 min of incubation with ionomycin, when the membrane skeleton-bound PFK was activated. Longer incubation time resulted in solubilization of the membrane skeleton-bound PFK and a concomitant hemolysis of the erythrocytes. These results suggest that the Ca2+ induced activation of membrane skeleton-bound PFK, and thereby glycolysis, the sole source of energy in erythrocytes, may be a defense mechanism to surmount the damage induced by high Ca2+ levels. PMID- 9973549 TI - Genome-wide scan for CAG/CTG repeat expansions in Pimas with early onset of type 2 diabetes mellitus. AB - The expansion of polymorphic CAG/CTG repeats in specific genes causes several neurodegenerative disorders and in many instances the length of the disease causing repeat correlates with the onset age and/or severity of symptoms. Type 2 diabetes mellitus has features in common with diseases resulting from trinucleotide repeat expansion, including a variable age of disease onset and penetrance. We have investigated whether CAG/CTG repeat expansion contributes to the genetic etiology of type 2 diabetes in the Pima Indians, a population with the highest reported prevalence of this disease. Using the Repeat Expansion Detection (RED) method, we determined the size range in nondiabetic Pimas to be between (CAG)20 and (CAG)130 (mean repeat length = 195 bp), which is significantly larger than the mean size reported in Caucasians (150 bp). We compared the distribution of CAG/CTG repeat lengths among 40 Pimas with an early onset of type 2 diabetes (<22 years) and 38 nondiabetic subjects (>55 years). A 240-bp CAG/CTG RED product was found more frequently in early onset diabetics relative to nondiabetic controls (26% vs 11%), whereas a 210-bp band was more prominent in unaffected subjects (29% vs 13%); however, these differences were not statistically significant. In one Pima kindred, we also identified large RED products (>/=360 bp) that displayed intergenerational instability among family members. However, these expansions were not associated with diabetes or any other clinical abnormalities in the carriers. We conclude that this unstable CAG/CTG repeat may represent a novel locus, consisting of large, but apparently nonpathogenic, unstable sequences. PMID- 9973551 TI - Volume 64, number 3 (1998), in article no. GM982708, "Epstein-barr virus-infected marmoset cells transfected with c-myc Do not form lymphomas in mice with severe combined Immunodeficiency," by babak salimi, maurice R. G. O'Gorman, daina variakojis, moshe bendet, malka newman, elisheva poupko, and ben Z. Katz, pages 205-212 PMID- 9973550 TI - A novel luteinizing hormone receptor mutation in a patient with familial male limited precocious puberty: effect of the size of a critical amino acid on receptor activity. AB - Familial male-limited precocious puberty (FMPP) is a form of luteinizing hormone releasing hormone (LHRH)-independent isosexual precocious puberty caused by gain of-function mutations of the luteinizing hormone/chorionic gonadotropin receptor (hLHR). The most common mutation is 1733 A>G, which causes substitution of Asp 578 by Gly. In this study, a male infant presented at the age of 20 months with accelerated sexual development was analyzed for the presence of activating mutations of the hLHR. Analysis of exon 11 of the hLHR gene by genomic polymerase chain reaction (PCR), asymmetric PCR, and dideoxy sequencing identified a single base substitution, 1734 T>A, which led to the replacement of Asp-578 by Glu. The same mutation was found in the mother. Expression of the mutated hLHR in HEK 293 cells demonstrated elevated basal levels of intracellular cAMP in the transfected cells confirming the constitutive activating nature of the mutated hLHR. A possible genotype-phenotype relationship of the hLHR mutations was examined by a comparison of the in vitro activities of the hLHRs carrying the Asp578Gly, Asp578Tyr, Asp578Trp, and Asp578Glu mutations in HEK 293 cells. A positive correlation between the size of the substituting amino acid and the basal level of intracellular cAMP of cells expressing the mutated receptor was demonstrated. PMID- 9973552 TI - Phosphorylation of either crh or HPr mediates binding of CcpA to the bacillus subtilis xyn cre and catabolite repression of the xyn operon. AB - Carbon catabolite repression (CCR) of several Bacillus subtilis catabolic genes is mediated by ATP-dependent phosphorylation of Ser46 of the histidine-containing protein (HPr), a phosphocarrier protein of the phosphoenolpyruvate (PEP): sugar phosphotransferase system. A recently discovered HPr-like protein of B. subtilis, Crh, cannot be phosphorylated by PEP and enzyme I but becomes phosphorylated at Ser46 by the ATP-dependent, metabolite-activated HPr kinase. Genetic data suggested that Crh is also implicated in CCR. We here demonstrate that in a ptsH1 crh1 mutant, in which Ser46 of both HPr and Crh is replaced with an alanyl residue, expression of the beta-xylosidase-encoding xynB gene was completely relieved from CCR. No effect on CCR could be observed in strains carrying the crh1 allele, suggesting that under the experimental conditions P-Ser-HPr can substitute for P-Ser-Crh in CCR. By contrast, a ptsH1 mutant was slightly relieved from CCR of xynB, indicating that P-Ser-Crh can substitute only partly for P-Ser-HPr. Mapping experiments allowed us to identify the xyn promoter and a catabolite responsive element (cre) located 229 bp downstream of the transcription start point. Using DNase I footprinting experiments, we could demonstrate that similar to P-Ser-HPr, P-Ser-Crh stimulates binding of CcpA to the xyn cre. Fructose 1,6-bisphosphate was found to strongly enhance binding of the P-Ser-HPr/CcpA and P-Ser-Crh/CcpA complexes to the xyn cre, but had no effect on binding of CcpA alone. PMID- 9973553 TI - A mathematical model for synergistic eukaryotic gene activation. AB - The precise biochemical mechanism underlying the synergistic action of gene activators on eukaryotic transcription has eluded a solution, largely because of the technical difficulties inherent in analyzing the mechanics of a 2.5 MDa complex comprising greater than 50 polypeptide components. To complement the biochemical approach we have employed mathematical modeling as a means to understand the mechanism of synergy. Parameters relevant to activated transcription were varied in a simple biochemical system and the data were compared to the transcriptional response predicted by a multi-component statistical model. We found that the model achieved a consistent, semi quantitative description of the measured transcriptional response, and enabled the characterization and measurement of thermodynamic parameters in the in vitro system. The results provide evidence for the existence of cooperativity in the activation process beyond what would be predicted from one current model suggesting that activators function solely by simple recruitment of the general transcription machinery to the promoter. PMID- 9973554 TI - NF-Y histone fold alpha1 helices help impart CCAAT specificity. AB - NF-Y is a conserved trimeric transcriptional activator with an extremely high specificity for CCAAT boxes. The NF-YB and NF-YC subunits have histone fold motifs with a high degree of homology to NC2alpha/beta, a TBP-binding repressor. The histone fold is composed of three alpha helices, alpha1, alpha2, alpha3, separated by short loops. Structural data on core histones showed that alpha1 are involved in DNA-binding. To understand the molecular basis of NF-Y sequence specificity, we constructed deletion and swapping mutants, in which the alpha1 of NC2 and archeal HMfB, a bona fide histonic protein, was placed in NF-YB and NF YC. Our analysis indicates that (i) subunit interactions are normal; (ii) NF-YB NF-YC and NC2alpha/beta do not form heterodimers and NC2 cannot associate NF-YA. (iii) None of the NF-Y swaps can complex with TBP on a TATA box. (iv) Specific residues, R47 and K49 in NF-YC and N61 in NF-YB, are crucial for CCAAT-binding. We conclude that specificity of the NF-Y trimer is not due to NF-YA only, but stems in part from the contribution of the histone fold alpha1, particularly that of NF-YB. PMID- 9973555 TI - Conformational changes of the upstream DNA mediated by H-NS and FIS regulate E. coli RrnB P1 promoter activity. AB - The two proteins FIS and H-NS had previously been shown to regulate ribosomal RNA (rRNA) transcription by interacting with the promoter upstream DNA. FIS is known as an activator whereas H-NS had been demonstrated to function as a repressor. Details of the antagonistic control mechanisms are not yet solved. Here, we have addressed the question how the two proteins cooperate to exert both, positive and negative control of rRNA transcription. By mobility shift experiments and footprinting studies we show that FIS and H-NS binding sites partially overlap but appear to interact with different sites of a curved DNA helix. Although not mutually exclusive, the two proteins compete each other for binding. Both proteins, by changing the DNA curvature, effect circularization reactions of DNA fragments in different ways. Our results imply that binding of the proteins induces alternate DNA conformations with favourable or unfavourable topology for the formation of active transcription complexes. Together the findings presented here help to answer some of the open questions about the concerted molecular mechanism of transcription factors for the regulation of stable RNA synthesis. PMID- 9973556 TI - Probing the rRNA environment of ribosomal protein S5 across the subunit interface and inside the 30 S subunit using tethered Fe(II). AB - A newly developed 30 S subunit reconstitution system using a complete set of recombinant proteins was used to study the ribosomal RNA (rRNA) neighborhood of ribosomal protein S5 in 30 S subunits and 70 S ribosomes by directed hydroxyl radical probing. Using three cysteine-containing mutant S5 proteins derivatized with 1-(p-bromoacetamidobenzyl)-Fe(II)-EDTA, we expanded on experiments carried out earlier using a natural protein reconstitution system. Natural 16 S rRNA, Fe(II)-S5, and the other recombinant ribosomal proteins were reconstituted into 30 S subunits. Both 30 S subunits and 70 S ribosomes containing Fe(II)-S5 were purified, and hydroxyl radicals were generated in situ from the tethered Fe(II). In 30 S subunits, 16 S rRNA nucleotides targeted by two positions on S5, C21 and C99, were virtually identical to those observed in the previous work, supporting the validity of the recombinant protein reconstitution system for probing studies. Interestingly, new cleavages were detected using Fe(II)-C129-S5, possibly reflecting incorporation of more derivatized protein into 30 S subunits due to the increased reconstitution efficiency of the recombinant protein system. These newly targeted positions overlap, but are distinct from, those observed using Fe(II) tethered to C21, which is near C129 in the S5 structure. In 70 S ribosomes, the cleavage pattern of 16 S rRNA was very similar to that observed in 30 S subunits for all target sites except for the absence of those at the extreme 5' end of 16 S rRNA. Additionally, probing of 70 S ribosomes from Fe-C99-S5 results in cleavage of 23 S rRNA in the 1690-1770 region of domain IV. These data provide constraints for the three-dimensional location of nucleotides within domain IV of 23 S ribosomal RNA relative to known features of the 30 S subunit. PMID- 9973557 TI - ErmE methyltransferase recognizes features of the primary and secondary structure in a motif within domain V of 23 S rRNA. AB - The Erm methyltransferases confer resistance to macrolide, lincosamide and streptogramin B (MLS) antibiotics by methylation of a single adenosine base within bacterial 23 S ribosomal RNA. The ErmE methyltransferase, from the macrolide-producing bacterium Saccharopolyspora erythraea, recognizes a motif within domain V of the rRNA that specifically targets adenosine 2058 (A2058) for methylation. Here, we define the structure of the RNA motif by a combination of molecular genetics and biochemical probing. The core of the motif has the primary sequence 2056-GGAHA-2060, where H is any nucleotide except guanosine, and ErmE methylates at the adenosine in bold. For efficient recognition by ErmE, this sequence must be displayed within a particular secondary structure. An irregular stem (helix 73) is required immediately 5' to A2058, with an unpaired nucleotide, preferably a cytidine residue, at position 2055. Nucleotides 2611 to 2616 are collectively required to form part of the 3'-side of helix 73, but there is little or no restriction on the identities of individual nucleotides here. There are minor preferences in the identities of nucleotides 2051 to 2055 that are adjacent to the motif core, although their main role is in maintaining the irregular secondary structure. The essential elements of the ErmE motif are conserved in bacterial 23 S rRNAs, and thus presumably also form the recognition motif for other Erm methyltransferases. PMID- 9973558 TI - Sites of interaction of streptogramin A and B antibiotics in the peptidyl transferase loop of 23 S rRNA and the synergism of their inhibitory mechanisms. AB - Streptogramin antibiotics contain two active A and B components that inhibit peptide elongation synergistically. Mutants resistant to the A component (virginiamycin M1 and pristinamycin IIA) were selected for the archaeon Halobacterium halobium. The mutations mapped to the universally conserved nucleotides A2059 and A2503 within the peptidyl transferase loop of 23 S rRNA (Escherichia coli numbering). When bound to wild-type and mutant haloarchaeal ribosomes, the A and B components (pristinamycins IIA and IA, respectively) produced partially overlapping rRNA footprints, involving six to eight nucleotides in the peptidyl transferase loop of 23 S rRNA, including the two mutated nucleotides. An rRNA footprinting study, performed both in vivo and in vitro, on the A and B components complexed to Bacillus megaterium ribosomes, indicated that similar drug-induced effects occur on free ribosomes and within the bacterial cells. It is inferred that position 2058 and the sites of mutation, A2059 and A2503, are involved in the synergistic inhibition by the two antibiotics. A structural model is presented which links A2059 and A2503 and provides a structural rationale for the rRNA footprints. PMID- 9973559 TI - Mechanism-based inhibition of C5-cytosine DNA methyltransferases by 2-H pyrimidinone. AB - DNA duplexes in which the target cytosine base is replaced by 2-H pyrimidinone have previously been shown to bind with a significantly greater affinity to C5 cytosine DNA methyltransferases than unmodified DNA. Here, it is shown that 2-H pyrimidinone, when incorporated into DNA duplexes containing the recognition sites for M.HgaI-2 and M.MspI, elicits the formation of inhibitory covalent nucleoprotein complexes. We have found that although covalent complexes are formed between 2-H pyrimidinone-modified DNA and both M.HgaI-2 and M.MspI, the kinetics of complex formation are quite distinct in each case. Moreover, the formation of a covalent complex is still observed between 2-H pyrimidinone DNA and M.MspI in which the active-site cysteine residue is replaced by serine or threonine. Covalent complex formation between M.MspI and 2-H pyrimidinone occurs as a direct result of nucleophilic attack by the residue at the catalytic position, which is enhanced by the absence of the 4-amino function in the base. The substitution of the catalytic cysteine residue by tyrosine or chemical modification of the wild-type enzyme with N-ethylmaleimide, abolishes covalent interaction. Nevertheless the 2-H pyrimidinone-substituted duplex still binds to M.MspI with a greater affinity than a standard cognate duplex, since the 2-H pyrimidinone base is mis-paired with guanine. PMID- 9973560 TI - Identification of three aspartic acid residues essential for catalysis by the RusA holliday junction resolvase. AB - RusA is a Holliday junction resolvase encoded by the cryptic prophage DLP12 of Escherichia coli K-12 that can be activated to promote homologous recombination and DNA repair in resolution-deficient mutants lacking the RuvABC proteins. Database searches with the 120 amino acid residue RusA sequence identified 11 homologues from diverse species, including one from the extreme thermophile Aquifex aeolicus, which suggests that RusA may be of ancient bacterial ancestry. A multiple alignment of these sequences revealed seven conserved or invariant acidic residues in the C-terminal half of the E. coli protein. By making site directed mutations at these positions and analysing the ability of the mutant proteins to promote DNA repair in vivo and to resolve junctions in vitro, we identified three aspartic acid residues (D70, D72 and D91) that are essential for catalysis and that provide the first insight into the active-site mechanism of junction resolution by RusA. Substitution of any one of these three residues with asparagine reduces resolution activity >80-fold. The mutant proteins retain the ability to bind junction DNA regardless of the DNA sequence or of the mobility of the crossover. They interfere with the function of the RuvABC proteins in vivo, when expressed from a multicopy plasmid, an effect that is reproducible in vitro and that reflects the fact that the RusA proteins have a higher affinity for junction DNA in the presence of Mg2+ than do the RuvA and RuvC proteins. The D70N protein has a greater affinity for junctions in Mg2+ than does the wild-type, which indicates that the negatively charged carboxyl group of the aspartate residue plays a critical role at the active site of RusA. Electrostatic repulsions between D70, D72 and D91 may help to form a classical Mg2+-binding pocket. PMID- 9973561 TI - Toxic mutations in the recA gene of E. coli prevent proper chromosome segregation. AB - The recA gene of Escherichia coli is the prototype of the recA/RAD51/DMC1/uvsX gene family of strand transferases involved in genetic recombination. In order to find mutations in the recA gene important in catalytic turnover, a genetic screen was conducted for dominant lethal mutants. Eight single amino acid substitution mutants were found to prevent proper chromosome segregation and to kill cells in the presence or absence of an inducible SOS system. All mutants catalyzed some level of recombination and constitutively stimulated LexA cleavage. The mutations occur at the monomer-monomer interface of the RecA polymer or at residues important in ATP hydrolysis, implicating these residues in catalytic turnover. Based on an analysis of the E96D mutant, a model is presented in which slow RecA DNA dissociation prevents chromosome segregation, engendering lexA-independent, lethal filamentation of cells. PMID- 9973562 TI - On the in vivo function of the RecA ATPase. AB - The Escherichia coli RecA protein is the prototype of the RecA/RAD51/DMC1 family of strand transferases acting in genetic recombination. The E96D mutant was previously isolated in a screen for toxic recA mutants and was found to constitutively derepress the SOS genes and inhibit chromosome segregation in E. coli. Here, we have found that the E96D mutation lowers the RecA kcat value for ATP hydrolysis 100-fold. Use of this mutant reveals that the ATPase and branch migration activities of RecA are not necessarily required for catalyzing in vivo recombinational pairing and LexA cleavage. In addition to its effect on ATP hydrolysis, the mutation causes ATP to more strongly promote the transition to the biologically active, extended conformation of the RecA enzyme. The enhanced ATP binding is apparently the cause for a broader nucleic acid ligand specificity. The use of RNA and double-stranded DNA as cofactors for LexA cleavage could give rise to the inappropriate, constitutive derepression of the SOS genes. This underscores the need for the ATP affinity to be optimized so that RecA becomes selectively activated only during DNA repair and recombination through binding single-stranded DNA. PMID- 9973563 TI - Two distinct mechanisms operate in the reactivation of heat-denatured proteins by the mitochondrial Hsp70/Mdj1p/Yge1p chaperone system. AB - The yeast mitochondrial Hsp70, Ssc1p, functions as a molecular chaperone with its partner proteins, Mdj1p (DnaJ homologue) and Yge1p (GrpE homologue). We have purified a mature form of Ssc1p from yeast mitochondria and those of Mdj1p and Yge1p from Escherichia coli overexpresser cells. With these purified components of the mitochondrial Hsp70 chaperone system, we have succeeded in reconstituting their chaperone functions in the protection of firefly luciferase against thermal damage in vitro. Heat-denatured luciferase is prevented from irreversible aggregation and is maintained in a refolding-competent state by Ssc1p and/or Mdj1p at 42 degreesC. Luciferase denatured at 42 degreesC is actively reactivated by Ssc1p, Mdj1p and/or Yge1p after lowering the temperature to 25 degreesC. The reactivation process of heat-denatured luciferase shows two-phase kinetics. The slow refolding process requires either Ssc1p or Mdj1p at 42 degreesC but the presence of Ssc1p, Mdj1p and Yge1p, and ATP hydrolysis, is essential at 25 degreesC. The slow refolding of luciferase involves multiple rounds of formation and dissociation of the complex between luciferase and Mdj1p/Ssc1p. On the other hand, the fast refolding process is most enhanced when luciferase is incubated with Ssc1p alone at 42 degreesC, and it requires neither the assistance of Mdj1p and Yge1p nor ATP hydrolysis. We have observed a similar two-pathway reactivation of heat-denatured luciferase by the bacterial Hsp70 and the yeast cytosolic Hsp70 systems. PMID- 9973564 TI - The first gene in the biosynthesis of the polyketide antibiotic TA of Myxococcus xanthus codes for a unique PKS module coupled to a peptide synthetase. AB - The polyketide antibiotic TA is synthesized by the Gram negative bacterium Myxococcus xanthus in a multi-step process in which a unique glycine-derived molecule is used as a starter unit and elongated through the condensation of 11 acetate molecules by polyketide synthases (PKSs). Analysis of a 7.2 kb DNA fragment, encoding the protein that carries out the first condensation step, revealed that the fragment constitutes a single open reading frame, referred to as Ta1, which lacks the 5' and 3' ends and displays two regions of similarity to other proteins. The first 1020 amino acid residues at the N terminus of the polypeptide are similar to sequences of the large family of enzymes encoding peptide synthetases. They are followed by a second region displaying a high degree of similarity to type I PKS genes. The genetic analysis of this open reading frame is compatible with the proposed chemical structure of TA. The data indicate that the genes encoding TA have a modular gene organization, typical of a type I PKS system. The unusual feature of Ta1 is that the first PKS module of TA resides on the same polypeptide as the peptide synthetase functional unit. PMID- 9973565 TI - Characterization of the interactions between human cdc25C, cdks, cyclins and cdk cyclin complexes. AB - We have overexpressed and purified human dual-specificity phosphatase cdc25C from a prokaryotic expression system at high levels and in a soluble, active form, and have studied and quantified its potential to interact with cdks, cyclins and preformed cdk-cyclin complexes by fluorescence spectroscopy and size-exclusion chromatography. Our data indicate that human cdc25C forms stable complexes, through hydrophobic contacts, with cdk and cyclin monomers, as well as with preformed cdk-cyclin complexes. In vitro, cdc25C interacts with cyclin monomers with high affinity, with tenfold less affinity with cdks, and with intermediate affinity with cdk-cyclin complexes. Moreover, changes observed in the intrinsic fluorescence of cdks, cyclins and cdk-cyclin complexes upon interaction with cdc25C are indicative of concomitant conformational changes within cdks and cyclins. From our results, we propose that in vitro, in the presence of monomeric cdks and cyclins, cdc25C forms stable ternary complexes, first through a high affinity interaction with a cyclin, which may then help target cdc25C towards a cdk. We discuss the biological relevance of our results and propose that a similar, two-step mechanism of interaction between cdc25C and cdk-cyclin complexes may occur in vivo. PMID- 9973566 TI - The ectodomain of HA2 of influenza virus promotes rapid pH dependent membrane fusion. AB - To better understand the roles of different regions of influenza hemagglutinin in membrane fusion, we have studied the fusion properties of large unilamellar vesicles in the presence of constructs comprising the 127 amino acid ectodomain of the HA2 fragment (FHA2) as well as mutated forms of FHA2 containing single amino acid substitutions, the 95 amino acid truncated form of FHA2 lacking the N terminal fusion peptide (SHA2), the 20 amino acid N-terminal fusion peptide and the ten amino acid peptide corresponding to the kinked loop region of FHA2. The 100 nm liposomes were made from dioleoylphosphatidylethanolamine, dioleoylphosphatidylcholine and cholesterol in equimolar ratio. At pH 5 a high rate of lipid mixing was observed with FHA2 present, even at very low molar concentrations, whereas much lower rates were observed using the shorter constructs: SHA2, the fusion peptide, and the loop peptide. Concentrations of FHA2 which promoted extensive lipid mixing also induced leakage of aqueous contents. Marked effects of FHA2 were also observed with liposomes of egg phosphatidylcholine. All of the changes observed with the liposomes were highly pH-dependent, with only negligible changes occurring at pH 7. The results demonstrate the potent action of FHA2 in promoting lipid mixing and demonstrate the contribution of other regions of the ectodomain of FHA2, in addition to the fusion peptide, to the mechanism of acceleration of membrane fusion. The results also indicate that the pH dependence of fusion is not due solely to changes in the interactions between the HA1 and HA2 subunits. Thus, the "spring loaded energy" is not required to bring about the apposition of the two membranes, considering that FHA2 is already in its thermostable conformation. The acidic amino acid residues in the kinked loop region appear to play a particularly important role in the pH-dependent fusion process as demonstrated by the marked loss of lipid mixing activity of mutant forms of FHA2. PMID- 9973567 TI - Determination of the residence time of water molecules hydrating B'- DNA and B DNA, by one-dimensional zero-enhancement nuclear Overhauser effect spectroscopy. AB - The residence time of water in the minor groove of the d(CGCGAATTCGCG) duplex has been determined by a recent measurement combining nuclear Overhauser enhancements (NOE, ROE) and 17O relaxation dispersion. The time is in the range of nanoseconds, so that it may be measured by a rather simple method proposed here, namely the choice of conditions such that the NOE between the observed DNA proton and a nearby water proton is zero. This condition is realized when the residence time of the water molecule is 0.178 times the nuclear magnetic resonance period (e.g. 0.297 ns at 600 MHz). It may be achieved by varying the magnetic field and/or the temperature. The zero-NOE measurement may be performed by one dimensional NMR, and has therefore good sensitivity. We have developed excitation sequences which suppress two spurious contributions to the NOE: from neighboring exchangeable protons and from H3' protons whose chemical shift is close to that of water. The method is applied here to the comparison of residence times of water next to B-DNA and next to B'-DNA, the latter corresponding to better stacked, propeller-twisted base-pairs and a correspondingly narrower minor groove. In the minor groove of [d(CGCGAATTCGCG)]2, a B'-DNA duplex, the residence time of the water molecule next to H2 of adenine(6) (underlined), is 0.6 ns at 10 degreesC, in good agreement with the value obtained previously. The residence time is slightly but distinctly shorter for the water next to A5, suggesting non cooperative departure of these two molecules which are presumed to be part of the hydration spine. Near A5 and A4 of [d(AAAAATTTTT)]2, another B'-DNA duplex, the residence times are approximately twice as long, but the activation enthalpies are about the same, ca. 38 kJ/mol. The residence time in the minor groove of the regular B-DNA sequence d(CGCGATCGCG) was 0.3 ns at 10 degreesC, shorter than in the case of the B'-DNA sequences by factors of 2 and 4, respectively. The temperature dependence is less, with an activation enthalpy of 27 kJ/mol. The major groove residence times are comparable for the three sequences, and a few times shorter than those of minor groove water. A value of 0.36 ns, or even more in case of rotation of water, is obtained around -8 degreesC. The most striking aspect of these results is the relatively small difference in the residence times of reputedly fast and slow-exchanging water molecules bound to DNA in biological conditions. This suggests that the spine of hydration is perhaps not a major stabilizer of the B'-DNA structure as compared with B-DNA. PMID- 9973568 TI - Three-dimensional placement of the conserved 530 loop of 16 S rRNA and of its neighboring components in the 30 S subunit. AB - Nucleotides 518-533 form a loop in ribosomal 30 S subunits that is almost universally conserved. Both biochemical and genetic evidence clearly implicate the 530 loop in ribosomal function, with respect both to the accuracy control mechanism and to tRNA binding. Here, building on earlier work, we identify proteins and nucleotides (or limited sequences) site-specifically photolabeled by radioactive photolabile oligoDNA probes targeted toward the 530 loop of 30 S subunits. The probes we employ are complementary to 16 S rRNA nucleotides 517 527, and have aryl azides attached to nucleotides complementary to nucleotides 518, 522, and 525-527, positioning the photogenerated nitrene a maximum of 19-26 A from the complemented rRNA base. The crosslinks obtained are used as constraints to revise an earlier model of 30 S structure, using the YAMMP molecular modeling package, and to place the 530 loop region within that structure. PMID- 9973569 TI - NMR structure of Escherichia coli glutaredoxin 3-glutathione mixed disulfide complex: implications for the enzymatic mechanism. AB - Glutaredoxins (Grxs) catalyze reversible oxidation/reduction of protein disulfide groups and glutathione-containing mixed disulfide groups via an active site Grx glutathione mixed disulfide (Grx-SG) intermediate. The NMR solution structure of the Escherichia coli Grx3 mixed disulfide with glutathione (Grx3-SG) was determined using a C14S mutant which traps this intermediate in the redox reaction. The structure contains a thioredoxin fold, with a well-defined binding site for glutathione which involves two intermolecular backbone-backbone hydrogen bonds forming an antiparallel intermolecular beta-bridge between the protein and glutathione. The solution structure of E. coli Grx3-SG also suggests a binding site for a second glutathione in the reduction of the Grx3-SG intermediate, which is consistent with the specificity of reduction observed in Grxs. Molecular details of the structure in relation to the stability of the intermediate and the activity of Grx3 as a reductant of glutathione mixed disulfide groups are discussed. A comparison of glutathione binding in Grx3-SG and ligand binding in other members of the thioredoxin superfamily is presented, which illustrates the highly conserved intermolecular interactions in this protein family. PMID- 9973570 TI - Single molecule force spectroscopy of spectrin repeats: low unfolding forces in helix bundles. AB - Spectrin repeats fold into triple helical coiled-coils comprising approximately 106 amino acid residues. Using an AFM-related technique we measured the force required to mechanically unfold these repeats to be 25 to 35 pN. Under tension, individual spectrin repeats unfold independently and in an all-or-none process. The dependence of the unfolding forces on the pulling speed reveals that the corresponding unfolding potential is shallow with an estimated width of 1.5 nm. When the unfolded polypeptide strand is relaxed, several domains refold within less than a second. The unfolding forces of the alpha-helical spectrin domains are five to ten times lower than those found in domains with beta-fold, like immunoglobulin or fibronectin Ill domains, where the tertiary structure is stabilized by hydrogen bonds between adjacent strands. This shows that the forces stabilizing the coiled-coil lead to a mechanically much weaker structure than multiple hydrogen-bonded beta-sheets. PMID- 9973571 TI - Experimental evolution of a dense cluster of residues in tyrosyl-tRNA synthetase: quantitative effects on activity, stability and dimerization. AB - A dense cluster of eight residues was identified at the crossing of two alpha helices in tyrosyl-tRNA synthetase (TyrRS) from the thermophile Bacillus stearothermophilus. Its mechanism of evolution was characterized. Four residues of this cluster are not conserved in TyrRS from the mesophile Escherichia coli. The corresponding mutations were constructed in TyrRS(Delta1), a derivative of TyrRS from B. stearothermophilus in which the anticodon binding domain is deleted. Mutations I52L (i.e. Ile52 into Leu), M55L and L105V did not affect the activity of TyrRS(Delta1) in the pyrophosphate exchange reaction whereas T51P increased it. The kinetic stabilities of TyrRS(Delta1) and its mutant derivatives at 68.5 degreesC were determined from experiments of irreversible thermal precipitation. They were in the order L105V50 per round of selection. PMID- 9973576 TI - Hormonal modulation of phagocytosis and intracellular growth of Mycobacterium avium ss. paratuberculosis In bovine peripheral blood monocytes. AB - In this study, we evaluated the effects of several hormones (i.e. growth hormone, prolactin, vitamin D3, luteinizing hormone, oxytocin) on the phagocytosis and intracellular survival of Mycobacterium avium ss. paratuberculosis within bovine peripheral blood monocytes. Phagocytosis of M. avium ss. paratuberculosis declined in a dose-dependent manner when monocytes were exposed to increasing amounts of recombinant bovine growth hormone, with little phagocytosis occurring at a growth hormone concentration of 50 ng/ml. The other hormones tested had little effect on phagocytosis. Continuous exposure of bovine monocytes to bovine growth hormone (10 ng per ml) resulted in enhanced intracellular bacillary growth. This was detected within 3 days of monocyte infection, and resulted in a 1 Log10 greater number of M. avium ss. paratuberculosis in growth hormone treated, than control, monocytes at 12 days of infection. When monocytes were incubated with growth hormone for only the first 5 days of a 12 day incubation period, a further increase in bacillary multiplication was observed. A similar increase in bacillary multiplication was observed when M. avium ss. paratuberculosis monocytes were incubated with prolactin for the first 5 days of a 12 day incubation period. These data indicate that varying levels of growth hormone and prolactin can affect the intracellular multiplication of M. avium ss. paratuberculosis in bovine monocytes. PMID- 9973577 TI - Tetranucleotide repeats identify novel virulence determinant homologues in Neisseria meningitidis. AB - Numerous outer membrane components of Neisseria meningitidis and N. gonorrhoeae exhibit phase variable expression (the rapid, reversible on/off switching of phenotypic expression). Many of the genes encoding these outer membrane components contain simple repetitive DNA motifs (mononucleotides, dinucleotides, tetranucleotides and other repeats) which mediate this variation. One such repeat motif, the tetranucleotide 5;-(GCAA)n-3;, is associated with phase-variable LPS biosynthetic genes in the pathogen Haemophilus influenzae. We have previously shown that N. meningitidis strain MC58 contains this repeat motif in at least three distinct genetic loci. In this study all three of these loci were investigated: two were cloned and identified as novel loci and designated nmrep1 and nmrep2. The third locus was assigned to a previously cloned gene and here is designated nmrep3. The distribution of these loci, and the number of repeat units at each locus was investigated in a range of strains. This analysis revealed that the nmrep1 and nmrep2 loci are present in all 45 strains examined, with 41/45 containing nmrep3. Sequences associated with nmrep1 showed no homology with reported proteins, but amino acid sequences of open reading frames of nmrep2 and nmrep3 exhibited sequence homology to the adhesins Aida of Escherichia coli and Prn of Bordetella sppand IcsA of Shigella flexneri which is involved in intracellular spread. PMID- 9973578 TI - Streptococcus pyogenes strains containing emm12 and emm55 possess a novel gene coding for distantly related SIC protein. AB - Streptococcus pyogenes infection and acute glomerulonephritis (AGN), a non suppurtave disease, are endemic in the Aboriginal people of the Northern Territory (NT) of Australia. Vir typing, a locus-specific polymerase chain reaction (PCR)-based typing method [Gardiner, Hartas, Currie et al PCR Meth Appl 1995 4: 288-93], has revealed high divergence among the NT streptococcal strains. A total of 76 Vir types (VTs) representing about 95% of the NT isolates were screened for sic, a gene for streptococcal inhibitor of complement function, by PCR and hybridization. This revealed that seven VTs are positive for sic, and there are two classes of the gene: those closely related to sic (CRS) originally described by Akesson, Sjoholm & Bjorck [ J. Biol. Chem. 1996 271: 1081-8] and those distantly related to sic (DRS). Among the CRS-positive VTs, VT16, VT78 and VT91 have emm (gene for M protein) encoding type 1 M protein or related specificity, and VT8 and VT101 contain emm57 or related alleles. Chromosomal location of CRS in emm57 is different from that in emm1 or related strains. The DRS-positive VT18 and VT52 contained emm55 and emm12 respectively, which are phylogenetically related. Strains of S. pyogenes types 1, 12, 55 and 57 are known to be associated with AGN. Restricted distribution of CRS and DRS among the M types historically associated with AGN suggests that these sic alleles may have a role in AGN pathogenesis. PMID- 9973579 TI - Frequency of apolipoprotein E (APOE) allele types in patients with Chlamydia associated arthritis and other arthritides. AB - Genetic background is important in determining whether certain infecting bacteria disseminate to the joint and cause arthritis. We assessed whether APOE genotype is associated with the presence of DNA from Chlamydia or other bacteria in synovial tissues of patients with various arthritides. Nucleic acids from synovial tissues of 135 patients were screened by PCR for DNA from Chlamydia trachomatis, C. pneumoniae and other bacteria (pan-bacteria). APOE genotype was determined by a PCR-based method for all patients in each of four resulting groups comprised of about 35 individuals each, positive for C. trachomatis only, C. pneumoniae only, other bacteria, or no bacteria. RT-PCR was used to assess synovial APOE expression. The latter assays confirmed that APOE mRNA is present in synovial tissue. Determination of APOE genotype showed that patients PCR negative in all assays, and those positive in the C. trachomatis - and pan bacteria- (excluding Chlamydia) directed assays, had distributions of the APOE epsilon2, epsilon3 and epsilon4 alleles mirroring those of the general population (i.e. about 8%, 79% and 13%, respectively). In contrast, 68% of patients with C. pneumoniae DNA in synovium possessed a copy of the epsilon4 allele. These results indicate that no association exists between APOE genotype and synovial presence of C. trachomatis or other bacteria. However, individuals bearing at least one copy of the APOE epsilon4 allele may be at increased risk for synovial infection by C. pneumoniae. PMID- 9973580 TI - Vacuolating cytotoxin purified from Helicobacter pylori causes mitochondrial damage in human gastric cells. AB - We investigated the effects of vacuolating cytotoxin (VacA) prepared from Helicobacter pylori on the metabolism of gastric epithelial cells, AZ-521. VacA caused the ATP levels to decrease in a time-dependent manner; by approximately 20% in 6 h, 35% in 12 h and 50% in 24 h, at a concentration of 120 nM. This decrease was also dependent on the concentration of VacA. To evaluate the impairment of mitochondria by VacA, mitochondrial membrane potential was estimated by flow cytometric analysis using 3, 3'-dihexyloxacarbocyanine iodide as a substrate. VacA decreased membrane potential with the relative fluorescence intensity of AZ-521 cells in 6 h from 52+/-3 to 24+/-1. Treatment of the cells with bafilomycin A1, a specific inhibitor of vacuolar ATPase proton pump, showed no apparent effect on these changes in the levels of ATP and the mitochondrial membrane potential. Secondly, we estimated the effect of VacA on oxygen consumption. VacA inhibited oxygen consumption in AZ-521 cells: the levels of PO 2 in the medium of control cells decreased by 73% in 3 h and 37% in 6 h, whereas those in VacA-treated cells were 84% in 3 h and 59% in 6 h. Flow cytometric analysis showed the number of cells in the G0/G1 phase was increased by VacA. Taken together, VacA induced an inactivation of energy metabolism followed by mitochondrial damage, leading to impairment of the cell cycle in gastric epithelial cells. PMID- 9973582 TI - A Message from Preventive Medicine and Your Physician. PMID- 9973581 TI - Do movie stars encourage adolescents to start smoking? Evidence from California. AB - BACKGROUND: The purpose of this study was to examine the relationship between adolescents' favorite movie stars and their smoking status, controlling for variables associated with smoking initiation. METHODS: The 1996 California Tobacco Survey questioned 6,252 adolescents about their favorite stars, smoking history, exposure to smokers, rebelliousness, knowledge and attitudes regarding smoking, and cigarette advertising and promotion. The top 10 favorite stars were tested for differential preference between ever and never smokers, defined as those who had never puffed on a cigarette. Never smokers were categorized as susceptible or nonsusceptible to smoking. RESULTS: Favorite stars differed significantly among adolescent ever and never smokers. A majority of favorite stars of ever smokers smoked on and off screen compared to favorite stars of never smokers. In multivariate analyses, adolescent never smokers who preferred favorite stars of adolescent ever smokers were significantly more likely to be susceptible to smoking (OR = 1.35; 95% CI 1.12, 1.62), even after adjustment for known predictors of adolescent smoking and demographic variables. This effect was only slightly weaker than that of exposure to friends and family who smoke (OR = 1.45; 95% CI 1.13, 1.85). CONCLUSIONS: This study provides preliminary evidence that stars who smoke on and off screen may encourage youth to smoke. PMID- 9973583 TI - The protective effect of good physical fitness when young on the risk of impaired glucose tolerance when old. AB - BACKGROUND: The role of physical activity or fitness on preventing impaired glucose tolerance (IGT) has not been widely investigated. The present case control study examined the relationship between the occurrence of IGT in men in their 50s and the level of their physical fitness while in their 30s. METHODS: The subjects consisted of 38 male Japan Self-Defense Forces officials in their 50s who had IGT, as diagnosed by the 75-g oral glucose tolerance test, and 60 control individuals. Nine diabetics were included in the IGT cases. As an indicator of physical fitness between the ages of 30 and 39 years, we selected the best time recorded for each individual during that decade of life for the 1,500-m physical fitness test run. We calculated the odds ratio for IGT in relation to selected risk factors (including physical fitness), and a logistic regression analysis was used to adjust for possible confounding variables. RESULTS: The odds ratio (95% confidence interval, P value) for IGT with physical fitness in their 30s was 0.25 (0.11-0.58, P < 0.05). With adjustment for a parental history of diabetes and body mass index in both their 30s and their 50s, the odds ratio was 0.31 (0.11-0.86, P < 0.05). CONCLUSIONS: We concluded that the occurrence of IGT, including diabetes, in men in their 50s can be reduced by maintaining a high level of physical fitness while in their 30s. PMID- 9973584 TI - Insufficiently active Australian college students: perceived personal, social, and environmental influences. AB - BACKGROUND: A sustainable pattern of participation in physical activity is important in the maintenance of health and prevention of disease. College students are in transition from an active youth to a more sedentary adult behavior pattern. METHODS: We assessed self-reported physical activity and other characteristics in a sample of 2,729 male and female students (median age was 20 years) recruited from representative courses and year levels at four Australian College campuses. They were categorized as sufficiently or insufficiently active, using estimates of energy expenditure (kcal/week) derived from self-reported physical activity. Personal factors (self-efficacy, job status, enjoyment), social factors (social support from family/friends), and environmental factors (awareness of facilities, gym membership) were also assessed. RESULTS: Forty seven percent of females and 32% of males were insufficiently active. For females, the significant independent predictors of being insufficiently active were lower social support from family and friends, lower enjoyment of activity, and not working. For males, predictors were lower social support from family and friends, lower enjoyment of activity, and being older. CONCLUSIONS: Factors associated with physical activity participation (particularly social support from family and friends) can inform physical activity strategies directed at young adults in the college setting. PMID- 9973585 TI - Smoking cravings are reduced by self-massage. AB - BACKGROUND: Attempts at smoking cessation have been correlated with severe withdrawal symptoms, including intense cigarette cravings, anxiety, and depressed mood. Massage therapy has been shown to reduce anxiety and stress hormones and improve mood. METHOD: Twenty adult smokers (M age = 32.6) were randomly assigned to a self-massage treatment or a control group. The treatment group was taught to conduct a hand or ear self-massage during three cravings a day for 1 month. RESULTS: Self-reports revealed lower anxiety scores, improved mood, and fewer withdrawal symptoms. In addition, the self-massage group smoked fewer cigarettes per day by the last week of the study. CONCLUSIONS: The present findings suggest that self-massage may be an effective adjunct treatment for adults attempting smoking cessation to alleviate smoking-related anxiety, reduce cravings and withdrawal symptoms, improve mood, and reduce the number of cigarettes smoked. PMID- 9973586 TI - Potential errors resulting from sex and age difference in assessing family history of diabetes. AB - BACKGROUND: Diabetes mellitus occurs nearly exponentially with aging and its occurrence differs between men and women in adulthood. Therefore, the sex and age of family members should be considered in assessing the family history. In this report the effects of sex and age on the positivity of family history were estimated numerically. METHODS: Sex- and age-specific proportion of a positive history of diabetes mellitus among 24,273 family members was obtained from a questionnaire survey of 2,316 high school students in Japan. By analyzing the sex and age-specific proportion with the logistic regression model, odds ratios were estimated which indicated potential bias or misclassification resulting from sex and age differences. RESULTS: The odds ratios were 1.97 (95% confidence interval, 1.74-2.23) for the sex difference and 1.05 (95% confidence interval, 1.04-1.05) for an age difference of 1 year. This indicated that a male family member had a 1.97 times higher chance of having a positive history than a female member and that a positive history increased by (1.05)y, where y was age difference in years. CONCLUSION: A control for sex and age of family members will be required in assessing the family history of diabetes mellitus as a risk factor. PMID- 9973587 TI - Sociodemographic and personal characteristics of adolescents engaged in weight loss and weight/muscle gain behaviors: who is doing what? AB - BACKGROUND: Prevalence rates of behaviors aimed at weight loss and weight/muscle gain among adolescents were examined across sociodemographic and personal anthropometric variables to provide insight into these behaviors and identify high-risk subgroups. METHODS: A statewide representative sample of 7th, 9th, and 11th grade public school students from Connecticut completed a classroom administered survey on adolescent health in 1995-1996. The study sample in the present analysis included 9,118 adolescents. RESULTS: The most frequently reported weight control behavior was exercise followed by dieting. Disordered eating (vomiting, diet pills, laxatives, or diuretics) over the previous week was reported by 7.4% of the girls and 3.1% of the boys. Steroids were used by 0.5% of the girls and 2.3% of the boys. Girls in the highest BMI category were at greatest risk for disordered eating behaviors while boys in the lowest BMI category were at greatest risk for steroid use. African American and Hispanic girls were less likely than Caucasians to diet and exercise, but were more likely to report behaviors aimed at weight gain. Relatively high rates of disordered eating behaviors were reported by African American and Hispanic boys. Older girls reported slightly more dieting and disordered eating and less exercise than younger girls. Youth from low socioeconomic backgrounds were at greater risk for disordered eating than youth from high socioeconomic backgrounds. CONCLUSIONS: The findings suggest a need to widen our scope of thinking with regard to who is concerned with their body shape/size and at risk for engaging in potentially dangerous behaviors aimed at either weight loss or muscle gain. PMID- 9973588 TI - Evaluation of a motivational smoking cessation intervention for women in public health clinics. AB - BACKGROUND: A multicomponent motivational smoking cessation intervention was evaluated in 33 prenatal, family planning, and pediatric services in 12 public health clinics. Clinic-based intervention components were implemented by clinic personnel as part of routine medical visits. METHODS: The evaluation design included pre- and postintervention measurements of multiple study outcomes in a baseline (all clinics prior to the start of the intervention) and an experimental period (matchedpair random assignment of clinics to intervention or control conditions). Subjects were 683 (baseline) and 1,064 (experimental) smokers with measurements of smoking outcomes at both times. Mixed-effects regressions analyzed individual outcomes clustered within clinics and services. RESULTS: Control and intervention clinics had similar outcomes in the baseline period. In the experiment, outcomes improved in the intervention but not in the control clinics. Compared to controls, smokers exposed to the intervention were more likely to have quit (14.5 versus 7.7%) or take actions toward quitting and had higher mean action, stage of readiness, and motivation to quit scores. These positive effects persisted when clustering within clinics and services was controlled. CONCLUSIONS: This intervention, implemented by clinic personnel as part of routine medical visits, was effective under these natural conditions across different types of clinic service. PMID- 9973589 TI - Stage distributions for five health behaviors in the United States and Australia. AB - BACKGROUND: A key variable for the design of individual and public health interventions is the Stage of Change. The five stages of readiness to change are Precontemplation, Contemplation, Preparation, Action, and Maintenance. The distribution of individuals across the stages of change can provide a valuable tool for designing health interventions. METHODS: The pattern of distribution across the stages of change for five behavioral risk factors is presented from five independent surveys, two from the United States and three from Australia. The five risk factors are smoking, low fat diet, regular exercise, reducing stress, and losing weight. Identical single-item questionnaire items for staging health behaviors were used in all surveys. RESULTS: The stage distributions for the five risk factors were similar across the five independent samples. In general, the pattern of stage distributions was stable across health risk factors, gender, country, and sample. CONCLUSIONS: Single-item survey measures of stage of change that are readily applicable to population studies appear to provide important information about the population characteristics of readiness to change behavioral risk factors. The stability of these distributions suggests that interventions matched by stage may have broad applicability. PMID- 9973590 TI - Long-term effects of aerobic exercise on psychological outcomes. AB - BACKGROUND: Although the literature on increased physical fitness and psychological outcomes has grown large, a number of methodological limitations remain unaddressed. The present study was designed to address a number of these limitations while examining the short- and long-term psychological effects following completion of a 12-week aerobic fitness program using bicycle ergometry (and confirmed increases in fitness). METHOD: Following completion of a 12-week aerobic fitness program (and through 12 months of follow-up), 82 adult participants completed the Beck Depression Inventory, Profile of Mood States, State-Trait Anxiety Inventory, and the Tennessee Self-Concept Scale. Physiological measures used to assess changes in aerobic fitness were maximal work load, submaximal heart rate at a standard work load, predicted maximum oxygen uptake, and resting heart rate. RESULTS: Exercise participants experienced a positive fitness change and psychological improvement over the initial 12-week program compared to a control group. At 1 year follow-up, physiological and psychological benefits remained significantly improved from baseline. CONCLUSIONS: Overall, results indicate that exercise-induced increases in aerobic fitness have beneficial short-term and long-term effects on psychological outcomes. We postulate that participants in the exercise group did not increase the amount of weekly exercise they performed over the 12-month follow-up period and thus the maintenance of the psychological improvements occurred concurrent with equal or lesser amounts of exercise. PMID- 9973591 TI - Modification in Quetelet index five months after myocardial infarction: relevance of biographic and personality characteristics. AB - BACKGROUND: Obesity can be considered as a risk factor for (re-)occurrence of coronary heart disease. METHODS: The relationship between modification in quetelet index and personality characteristics was assessed in 166 survivors of a first myocardial infarction (MI). Quetelet index (weight/(height)2) was calculated a few days after first MI and again 5 months later. A multiple regression analysis was executed, with the quetelet index after 5 months as dependent variable and adjustment for gender, age, and quetelet index at baseline. RESULTS: It was found that strong feelings of vital exhaustion and lack of tension significantly contributed to the prediction of increased quetelet index 5 months after a first MI. CONCLUSIONS: It is recommended that individually tailored interventions be used based on these personality characteristics to accomplish body weight reduction in MI patients. PMID- 9973592 TI - Hepatitis C in state correctional facilities. AB - BACKGROUND: No previous studies have examined the extent to which correctional facilities in the United States screen for and treat hepatitis C (HCV) infection. METHODS: Medical directors of state correctional facilities responded to a survey assessing the degree to which prisons screen for and treat hepatitis C. To estimate numbers of inmates eligible for interferon treatment and to examine costs associated with HCV management, we constructed a feasibility model that incorporated screening criteria used in California and Rhode Island. RESULTS: Thirty-six states and Washington, DC, responded, resulting in a survey response rate of 73%, representing 77% of all inmates in state facilities nationwide. Colorado alone reported routine screening. Only California reported conducting a systematic seroprevalence study, which found that 39.4% of male inmates were hepatitis C antibody positive in 1994. Seventy-three percent of the respondents sometimes consider treating with interferon. Four states follow a standard protocol. The feasibility model suggests that treating suitably screened inmates is a reasonable expenditure for correctional systems. CONCLUSION: Prison may be an appropriate setting for treatment of hepatitis C. If accompanying substance abuse issues are addressed, instituting HCV treatment for certain eligible incarcerated individuals may be a worthy target for public health dollars. PMID- 9973593 TI - Effects of a lifestyle exercise intervention. PMID- 9973594 TI - Forward and retrograde trafficking in mitotic animal cells. ER-Golgi transport arrest restricts protein export from the ER into COPII-coated structures. AB - Protein transport arrest occurs between the ER and Golgi stack of mitotic animal cells, but the location of this block is unknown. In this report we use the recycling intermediate compartment protein ERGIC 53/p58 and the plasma membrane protein CD8 to establish the site of transport arrest. Recycled ERGIC 53/p58 and newly synthesised CD8 accumulate in ER cisternae but not in COPII-coated export structures or more distal sites. During mitosis the tubulovesicular ER-related export sites were depleted of the COPII component Sec13p, as shown by immunoelectron microscopy, indicating that COPII budding structures are the target for mitotic inhibition. The extent of recycling of Golgi stack residents was also investigated. In this study we used oligosaccharide modifications on CD8 trapped in the ER of mitotic cells as a sensitive assay for recycling of Golgi stack enzymes. We find that modifications conferred by the Golgi stack-resident GalNac transferase do occur on newly synthesised CD8, but these modifications are entirely due to newly synthesised transferase rather than to enzyme recycled from the Golgi stack. Taken together our findings establish for the first time that the site of ER-Golgi transport arrest of mitotic cells is COPII budding structures, and they clearly speak against a role for recycling in partitioning of Golgi stack proteins via translocation to the ER. PMID- 9973595 TI - Formation of a primitive ectoderm like cell population, EPL cells, from ES cells in response to biologically derived factors. AB - The primitive ectoderm of the mouse embryo arises from the inner cell mass between 4.75 and 5.25 days post coitum, around the time of implantation. Positioned at a pivotal time in development, just prior to formation of the three germ layers of the embryo proper, the primitive ectoderm responds directly to the signals generated during gastrulation. We have identified a conditioned medium, MEDII, which caused the homogeneous conversion of ES cells to a morphologically distinct cell population, termed early primitive ectoderm-like (EPL) cells. EPL cells expressed the pluripotent cell markers Oct4, SSEA1 and alkaline phosphatase. However, the formation of EPL cells was accompanied by alterations in Fgf5, Gbx2 and Rex1 expression, a loss in chimaera forming ability, changes in factor responsiveness and modified differentiation capabilities, all consistent with the identification of EPL cells as equivalent to the primitive ectoderm population of the 5.5 to 6.0 days post coitum embryo. EPL cell formation could be reversed in the presence of LIF and withdrawal of MEDII, which suggested that EPL cell formation was not a terminal differentiation event but reflected the ability of pluripotent cells to adopt distinct cell states in response to specific factors. Partial purification of MEDII revealed the presence of two separable biological activities, both of which were required for the induction and maintenance of EPL cells. We show here the first demonstration of uniform differentiation of ES cells in response to biological factors. The formation of primitive ectoderm, both in vivo and in vitro, appears to be an obligatory step in the differentiation of the inner cell mass or ES cells into cell lineages of the embryonic germ layers. EPL cells potentially represent a model for the development of lineage specific differentiation protocols and analysis of gastrulation at a molecular level. An understanding of the active components of MEDII may provide a route for the identification of factors which induce primitive ectoderm formation in vivo. PMID- 9973596 TI - The cellular basis of corneal transparency: evidence for 'corneal crystallins'. AB - In vivo corneal light scattering measurements using a novel confocal microscope demonstrated greatly increased backscatter from corneal stromal fibrocytes (keratocytes) in opaque compared to transparent corneal tissue in both humans and rabbits. Additionally, two water-soluble proteins, transketolase (TKT) and aldehyde dehydrogenase class 1 (ALDH1), isolated from rabbit keratocytes showed unexpectedly abundant expression ( approximately 30% of the soluble protein) in transparent corneas and markedly reduced levels in opaque scleral fibroblasts or keratocytes from hazy, freeze injured regions of the cornea. Together these data suggest that the relatively high expressions of TKT and ALDH1 contribute to corneal transparency in the rabbit at the cellular level, reminiscent of enzyme crystallins in the lens. We also note that ALDH1 accumulates in the rabbit corneal epithelial cells, rather than ALDH3 as seen in other mammals, consistent with the taxon-specificity observed among lens enzyme-crystallins. Our results suggest that corneal cells, like lens cells, may preferentially express water soluble proteins, often enzymes, for controlling their optical properties. PMID- 9973597 TI - Regulation of c-met expression in B16 murine melanoma cells by melanocyte stimulating hormone. AB - B16 murine melanoma cells selected in vivo for enhanced liver metastatic ability (B16-LS9) show on the one hand an increased expression and constitutive activation of the proto-oncogene c-met (the receptor for hepatocyte growth factor/scatter factor), and on the other hand a more differentiated phenotype, when compared to the parental cell line, B16-F1. Following this observation, we have tried to establish whether there is a direct relationship between differentiation and c-met expression in B16 melanoma cells. Treatment of these cells with differentiating agents indicated that c-met expression was strongly induced by melanocyte stimulating hormone, while retinoic acid had almost no influence. c-met induction was triggered by engagement of the melanocortin receptor, cAMP elevation and PKA/PKC(&agr;) activation, as respectively shown by the effects of ACTH, cAMP elevating agents and specific PK inhibitors. Regulation of c-met expression via the melanocortin receptor and cAMP raises the intriguing possibility that autocrine and/or paracrine mechanisms acting in vivo on this circuit might influence (through c-met expression and activation) the metastatic behavior of these tumor cells, which we have shown to be dependent on their c-met expression. PMID- 9973598 TI - Phosphatidylinositol 3-kinase translocation to the nucleus is induced by interleukin 1 and prevented by mutation of interleukin 1 receptor in human osteosarcoma Saos-2 cells. AB - Although interleukin 1 (IL-1) functions have been extensively characterized, the mechanisms by which IL-1 signals are transduced from the plasma membrane to the nucleus are less known. Recent evidence indicates that phosphatidylinositol 3 kinase (PI3-kinase) could be activated by a direct association with the activated IL-1 receptor. In this study we analyzed the effects of IL-1 on the intracellular distribution of PI3-kinase in wild-type Saos-2 human osteosarcoma cells, and in cell clones overexpressing type I IL-1 receptor (IL-1RI). PI3-kinase intracellular distribution displays two distinct patterns. In quiescent cells, PI3-kinase is distributed through the cytoplasm, although a portion is present in the nucleus; following stimulation with IL-1, PI3-kinase is redistributed, increasing in the nuclear compartment. Both immunoblotting and immunofluorescence data indicate that IL-1 causes a rapid and transient translocation of PI3-kinase from the cytoplasm to the nucleus. This phenomenon is prevented by PI3-kinase inhibitors, suggesting that the maintenance of PI3-kinase activity is essential for IL-1-induced translocation. Indeed, in cell clones stably transfected with Y479F receptor mutant, in which the binding of the enzyme to the activated receptor is blocked, IL-1-induced PI3-kinase translocation to the nucleus is completely prevented. These data suggest that PI3-kinase translocation to the nucleus upon IL-1R activation is an early event in IL-1 signaling mechanism, and may be involved in transcriptional activation. PMID- 9973599 TI - Rab3 is present on endosomes from bovine chromaffin cells in primary culture. AB - Rab3a, a small GTP-binding protein, is believed to mediate Ca2+-dependent exocytosis. Consistent with such a role was the previously reported specific association of Rab3a with synaptic vesicles in neurons and secretory granules in adrenal chromaffin cells. Secretory vesicles are believed to be the final point of Rab3a membrane association, as it was shown by several groups that Rab3a dissociates from the secretory vesicle membrane during stimulated exocytosis. In chromaffin cells, Rab3a is not exclusively localized on secretory granules since a fraction is present on a previously unidentified subcellular compartment equilibrating at light sucrose density. This 'light' membraneous structure could be the starting point for reassociation of Rab3a with membranes involved in granule formation, or it could be a structure unrelated to granules. The present study used several subcellular fractionation techniques and immunomicroscopy to unravel the nature of the 'light' Rab3a-containing structures from bovine chromaffin cells in primary culture. After stimulation, amounts of both Rab3a-d and the granule marker dopamine-beta-hydroxylase (DbetaH) increase transiently in sucrose gradient fractions enriched in endosomal markers. A diaminobenzidine induced density shift of endosomes alters the distribution of DbetaH and Rab3a-d. At the ultrastructural level, subplasmalemmal pleiomorphic organelles were detected by Rab3a-d-immunogold labelling. Taken together our data provide for the first time evidence that internalised secretory granule membranes go through an endosomal stage where Rab3a is present, resembling the neuronal synaptic vesicle cycle. This indicates that the endosome is an important trafficking route in the biogenesis/recycling of secretory vesicles in chromaffin cells, in which Rab3a could have an as yet unknown regulatory function, and could point to the existence of alternative recycling pathways for the chromaffin granule membrane. PMID- 9973600 TI - Bouquet formation in budding yeast: initiation of recombination is not required for meiotic telomere clustering. AB - Fluorescence in situ hybridization in combination with synaptonemal complex and spindle pole body immunostaining to both spread and structurally preserved nuclei from time course experiments disclosed prominent telomere clustering during meiotic prophase of the yeast Saccharomyces cerevisiae. It was found that centromere clustering, which dominates vegetative nuclear structure, is rapidly lost after induction of meiosis. Telomeres tightly clustered during leptotene/zygotene-equivalent stages in the vicinity of the spindle pole body, giving rise to a classical chromosomal bouquet arrangement. This arrangement dissolved later during prophase. Painting of chromosomes XI revealed that initially compacted chromosome territories adopt an outstretched morphology in bouquet nuclei. This conformational state was associated with alignment and pairing. Chromosome condensation during pachytene rendered condensed and compact bivalents, and dispersed telomeres. Both the spo11 and rad50S recombination mutants formed bouquets, demonstrating that bouquet formation is recombination and synapsis independent. PMID- 9973601 TI - Cytological characterisation of the mutant phenotypes produced during early embryogenesis by null and loss-of-function alleles of the gammaTub37C gene in Drosophila. AB - We have studied the mutant phenotypes brought about during early embryogenesis by mutation in the gammaTub37C gene, one of the two isoforms of gamma-tubulin that have been identified in Drosophila. We have focused our attention on fs(2)TW1(1) and fs(2)TW1(RU34), a null and a hypomorph allele of this gene, whose sequences we report in this work. We have found that the abnormal meiotic figures observed in mutant stage 14 oocytes are not observed in laid oocytes or fertilised embryos, suggesting that these abnormal meiotic figures are not terminally arrested. We have also concluded that both null and hypomorph alleles lead to a total arrest of nuclear proliferation during early embryogenesis. This is in contrast to their effect on female meiosis-I where hypomorph alleles display a much weaker phenotype. Finally, we have observed that null and hypomorph alleles lead to some distinct phenotypes. Unfertilised laid oocytes and fertilised embryos deficient for gammaTub37C do not contain polar bodies and have a few bipolar microtubule arrays. In contrast, oocytes and embryos from weaker alleles do not have these microtubule arrays, but do contain polar bodies, or polar-body like structures. These results indicate that gammaTub37C is essential for nuclear proliferation in the early Drosophila embryo. PMID- 9973602 TI - Underexpression of the 43 kDa inositol polyphosphate 5-phosphatase is associated with spontaneous calcium oscillations and enhanced calcium responses following endothelin-1 stimulation. AB - The 43 kDa inositol polyphosphate 5-phosphatase (5-phosphatase) hydrolyses the signalling molecules inositol 1,4,5-trisphosphate (Ins(1,4,5)P3) and inositol 1,3,4,5-tetrakisphosphate (Ins(1,3,4, 5)P4) and thereby regulates cellular transformation. To investigate the role Ins(1,4,5)P3-mediated Ca2+ oscillations play in cellular transformation, we studied Ins(1,4,5)P3-mediated Ca2+ responses in cells underexpressing the 43 kDa 5-phosphatase. Chronic reduction in 43 kDa 5 phosphatase enzyme activity resulted in a 2.6-fold increase in the resting Ins(1,4,5)P3 concentration and a 4.1-fold increase in basal intracellular Ca2+. The increased Ins(1,4,5)P3 levels resulted in partial emptying (40%) of the Ins(1,4,5)P3-sensitive Ca2+ store, however, store-operated Ca2+ influx remained unchanged. In addition, Ins(1,4,5)P3 receptors were chronically down-regulated in unstimulated cells, as shown by a 53% reduction in [3H]Ins(1,4,5)P3 binding to microsomal receptor sites. Agonist stimulation with endothelin-1 resulted in the rapid rise and fall of Ins(1,4,5)P3 and Ins(1,3,4,5)P4 levels, with no significant differences in the rates of hydrolysis of these second messengers in antisense- or vector-transfected cells. These studies indicate, in contrast to its predicted action, the 43 kDa 5-phosphatase does not metabolise Ins(1, 4,5)P3 and Ins(1,3,4,5)P4 post agonist stimulation. Cells with decreased 43 kDa 5 phosphatase activity exhibited spontaneous Ca2+ oscillations in the absence of any agonist stimulation, and increased sensitivity and amplitude of intracellular Ca2+ responses to both high and low dose endothelin-1 stimulation. We conclude the 43 kDa 5-phosphatase exerts a profound influence on Ins(1,4, 5)P3-induced Ca2+ spiking, both in the unstimulated cell and following agonist stimulation. We propose the enhanced Ca2+ oscillations may mediate cellular transformation in cells underexpressing the 43 kDa 5-phosphatase. PMID- 9973603 TI - Parasitophorous vacuoles of Leishmania mexicana acquire macromolecules from the host cell cytosol via two independent routes. AB - The intracellular parasite Leishmania survives and proliferates in host macrophages. In this study we show that parasitophorous vacuoles of L. mexicana gain access to cytosolic material via two different routes. (1) Small anionic molecules such as Lucifer Yellow are rapidly transported into the vacuoles by an active transport mechanism that is sensitive to inhibitors of the host cell's organic anion transporter. (2) Larger molecules such as fluorescent dextrans introduced into the host cell cytosol are also delivered to parasitophorous vacuoles. This transport is slower and sensitive to modulators of autophagy. Infected macrophages were examined by two novel assays to visualize and quantify this process. Immunoelectron microscopy of cells loaded with digoxigenin-dextran revealed label in multivesicular endosomes, which appeared to fuse with parasitophorous vacuoles. The inner membranes of the multivesicular vesicles label strongly with antibodies against lysobisphosphatidic acid, suggesting that they represent a point of confluence between the endosomal and autophagosomal pathways. Although the rate of autophagous transfer was comparable in infected and uninfected cells, infected cells retained hydrolyzed cysteine proteinase substrate to a greater degree. These data suggest that L. mexicana-containing vacuoles have access to potential nutrients in the host cell cytosol via at least two independent mechanisms. PMID- 9973604 TI - Integrin and cytoskeletal regulation of growth factor signaling to the MAP kinase pathway. AB - Integrin-mediated anchorage of NIH3T3 fibroblasts to the extracellular matrix component fibronectin permits efficient growth factor signaling to the p42 and p44 forms of mitogen-activated protein kinase (MAPK). Since integrins bridge the extracellular matrix to focal adhesion sites and to the actin cytoskeleton, we analyzed the role of these integrin-associated structures in efficient growth factor activation of p42 and p44-MAPKs. Use of specific reagents that disrupt actin stress fiber and focal adhesion formation demonstrated that upon readhesion of NIH3T3 cells to fibronectin, cells that were poorly spread and lacked prominent focal adhesions but that formed cortical actin structures, efficiently signaled to p42 and p44-MAPKs upon EGF stimulation. In contrast, failure to form the cortical actin structures, despite attachment to fibronectin, precluded effective EGF signaling to p42 and p44-MAPKs. Actin cytoskeletal changes induced by expression of dominant-negative and constitutively active forms of Rho GTPases did not alter EGF activation of MAPK in adherent cells. However, active Cdc42, but not active Rac1 or RhoA, partially rescued EGF signaling to p44-MAPK in cells maintained in suspension. These data indicate that a limited degree of adhesion mediated cytoskeletal organization and focal adhesion complex formation are required for efficient EGF activation of p42 and p44-MAPKs. Our studies exclude a major role for the GTPases RhoA and Rac1 in the formation of cytoskeletal structures relevant for signaling, but indicate that structures regulated by Cdc42 enhance the ability of suspension cells to activate MAPK in response to growth factors. PMID- 9973605 TI - Cytocentrin is a Ral-binding protein involved in the assembly and function of the mitotic apparatus. AB - Cytocentrin is a cytosolic protein that transiently associates with the mitotic spindle poles in early prophase, and dissociates from them after completion of mitosis. Cloning of its cDNA demonstrated a high degree of homology with three proteins known to specifically interact with an activated form of Ral. Herein we demonstrate that overexpression of cytocentrin inhibits assembly of the mitotic spindle without affecting polymerization or distribution of interphase microtubules. Conversely, loss of cytocentrin expression leads to formation of monopolar spindles. These results indicate that association of cytocentrin with the centrosome may be essential for a timely separation of the diplosomes. They also implicate Ral GTPases and their related pathways in the assembly and function of the mitotic apparatus. PMID- 9973606 TI - The mechanism of facilitated cell membrane resealing. AB - Disruption of the plasma membrane evokes an exocytotic response that is required for rapid membrane resealing. We show here in Swiss 3T3 fibroblasts that a second disruption at the same site reseals more rapidly than the initial wound. This facilitated response of resealing was inhibited by both low external Ca2+ concentration and specific protein kinase C (PKC) inhibitors, bisindolylmaleimide I (BIS) and Go-6976. In addition, activation of PKC by phorbol ester facilitated the resealing of a first wound. BIS and Go-6976 suppressed the effect of phorbol ester on resealing rate. Fluorescent dye loss from a FM1-43 pre-labeled endocytotic compartment was used to investigate the relationship between exocytosis, resealing and the facilitation of resealing. Exocytosis of endocytotic compartments near the wounding site was correlated with successful resealing. The destaining did not occur when exocytosis and resealing were inhibited by low external Ca2+ concentration or by injected tetanus toxin. When the dye loaded cells were wounded twice, FM1-43 destaining at the second wound was less than at the first wound. Less destaining was also observed in cells pre treated with phorbol ester, suggesting newly formed vesicles, which were FM1-43 unlabeled, were exocytosed in the resealing at repeated woundings. Facilitation was also blocked by brefeldin A (BFA), a fungal metabolite that inhibits vesicle formation at the Golgi apparatus. Lowering the temperature below 20 degrees C also blocked facilitation as expected from a block of Golgi function. BFA had no effect on the resealing rate of an initial wound. The facilitation of the resealing by phorbol ester was blocked by pre-treatment with BFA. These results suggest that at first wounding the cell used the endocytotic compartment to add membrane necessary for resealing. At a second wounding, PKC, activated by Ca2+ entry at the first wound, stimulated vesicle formation from the Golgi apparatus, resulting in more rapid resealing of the second membrane disruption. Since vesicle pools were implicated in both membrane resealing and facilitation of membrane resealing, we reasoned that artificial decreases in membrane surface tension would have the same result. Decreases in surface tension induced by the addition of a surfactant (Pluronic F68 NF) or cytochalasin D facilitated resealing at first wounding. Furthermore, Pluronic F68 NF restored resealing when exocytosis was blocked by tetanus toxin. These results suggest that membrane resealing requires a decrease in surface tension and under natural conditions this is provided by Ca2+-dependent exocytosis of new membrane near the site of disruption. PMID- 9973607 TI - Splice variants of the nuclear dot-associated Sp100 protein contain homologies to HMG-1 and a human nuclear phosphoprotein-box motif. AB - Sp100 and PML are interferon-inducible proteins associated with a new class of nuclear domains (known as nuclear dots or PML bodies) which play a role in tumorigenesis, virus infections, and autoimmunity. While PML is extensively alternatively spliced, only two splice variants are known for Sp100. Here we describe the identification and characterization of several Sp100 splice variant proteins and support their existence by elucidation of the 3'-end of the Sp100 gene. Some of the splice variants contain a domain of significant sequence similarity with two previously described highly related interferon-inducible nuclear phosphoproteins as well as to suppressin and DEAF-1, which altogether define a novel protein motif, termed HNPP-box. One class of splice variants contains an almost complete and highly conserved copy of the DNA-binding high mobility group 1 protein sequence and thus represent novel HMG-box proteins. When expressed transiently, both major classes of Sp100 splice variant proteins localize in part to nuclear dots/PML bodies and in addition to different nuclear domains. Furthermore, PML was occasionally redistributed. These data indicate that alternatively spliced Sp100 proteins are expressed, differ in part in localization from Sp100, and might bind to chromatin via the HMG domain. PMID- 9973608 TI - Molecular characterization and developmentally regulated expression of Xenopus lamina-associated polypeptide 2 (XLAP2). AB - Lamina-associated polypeptides 2 (LAP2alpha, beta, gamma)/thymopoietins (TPalpha, beta, gamma) are a family of proteins that are generated by alternative splicing from a single gene. These proteins have been primarily characterized in mammals. One member of this protein family, the integral membrane protein LAP2beta/TPbeta, has been localized to the inner nuclear membrane of somatic cells where it binds to chromatin and B-type lamins. By cDNA cloning we have characterized XLAP2, a Xenopus homologue of the mammalian LAP2beta. Using LAP2-specific antibodies, the Mr 68,000 XLAP2 was found to be the only member of the LAP2/TP family expressed in somatic cells and adult tissues. XLAP2 was not detected in oocytes, eggs and in early embryos up to the gastrula stage at the mRNA and protein level demonstrating that it is not synthesized from maternal mRNA. In counterpart oocytes, eggs, and embryos contained one LAP2-related integral membrane proteins of Mr 84,000. Northern blot analysis with the XLAP2 cDNA showed that a single hybridizing mRNA band of 1.8-2.0 kb was present in Xenopus somatic cells whereas two other hybridizing mRNA species of 2.8-3.0 and 0. 9-1.1 kb were present in oocytes, eggs and early embryos. All together, these results indicated that at least three distinct LAP2-related proteins might be expressed in Xenopus. The LAP2/TP protein of Mr 84,000 is present in the early embryos but its amount decreases during embryogenesis concomitant with the increase of XLAP2 in the embryo. Our results are the first description of the developmentally regulated expression of integral nuclear envelope proteins during early embryogenesis. PMID- 9973609 TI - Conserved domains in DNA repair proteins and evolution of repair systems. AB - A detailed analysis of protein domains involved in DNA repair was performed by comparing the sequences of the repair proteins from two well-studied model organisms, the bacterium Escherichia coli and yeast Saccharomyces cerevisiae, to the entire sets of protein sequences encoded in completely sequenced genomes of bacteria, archaea and eukaryotes. Previously uncharacterized conserved domains involved in repair were identified, namely four families of nucleases and a family of eukaryotic repair proteins related to the proliferating cell nuclear antigen. In addition, a number of previously undetected occurrences of known conserved domains were detected; for example, a modified helix-hairpin-helix nucleic acid-binding domain in archaeal and eukaryotic RecA homologs. There is a limited repertoire of conserved domains, primarily ATPases and nucleases, nucleic acid-binding domains and adaptor (protein-protein interaction) domains that comprise the repair machinery in all cells, but very few of the repair proteins are represented by orthologs with conserved domain architecture across the three superkingdoms of life. Both the external environment of an organism and the internal environment of the cell, such as the chromatin superstructure in eukaryotes, seem to have a profound effect on the layout of the repair systems. Another factor that apparently has made a major contribution to the composition of the repair machinery is horizontal gene transfer, particularly the invasion of eukaryotic genomes by organellar genes, but also a number of likely transfer events between bacteria and archaea. Several additional general trends in the evolution of repair proteins were noticed; in particular, multiple, independent fusions of helicase and nuclease domains, and independent inactivation of enzymatic domains that apparently retain adaptor or regulatory functions. PMID- 9973610 TI - The evolutionary scrambling and developmental unscrambling of germline genes in hypotrichous ciliates. AB - Genes in the germline (micronuclear) genome of hypotrichous ciliates are interrupted by multiple, short, non-coding, AT-rich sequences called internal eliminated segments, or IESs. During conversion of a micronucleus to a somatic nucleus (macronucleus) after cell mating, all IESs are excised from the germline genes and the gene segments, called macronuclear-destined segments, or MDSs, are spliced. Excision of the approximately 150 000 IESs from a haploid germline genome in Oxytricha nova requires approximately 150 000 recombinant events. In three of 10 genes the MDSs are scrambled. During macronuclear development the MDSs are unscrambled, possibly by folding of the DNA to allow MDSs to ligate in the correct order. The nine MDSs in the actin I gene of O.nova are scrambled in the random order, 3-4-6-5-7-9-2-1-8, and MDS 2 is inverted. The 14 MDSs in the alphaTP gene of O.nova and Stylonychia mytilus are scrambled in the non-random order, 1-3-5-7-9-11-2-4-6-8-10-12-13-14. The 45 MDSs in the DNA pol alpha gene are non-randomly scrambled into an odd/even series, with an inversion of one third of the gene. Additional IESs have been inserted into these three genes during evolution of Oxytricha trifallax, slightly modifying scrambling patterns. The non-random scrambled patterns in the alphaTP and DNA pol alpha genes are explained by multiple, simultaneous IES insertions. The randomly scrambled pattern in the actin I gene may arise from an initially non-randomly scrambled pattern by recombination among multiple IESs. Alternatively, IESs inserted sporadically (individually) in a non-scrambled configuration might subsequently recombine, converting a non-scrambled gene into a randomly scrambled one. IESs shift along a DNA molecule, most likely as a result of mutations at MDS/IES junctions. Shifting of IESs has the effect of 'transferring' nucleotides from one MDS to another, but does not change the overall sequence of nucleotides in the combined MDSs. In addition to shifting in position, IESs accumulate mutations at a high rate and increase and decrease in length within a species and during speciation. The phenomena of IESs and of MDS scrambling represent remarkable flexibility of the hypotrich genome, possibly reflecting a process of MDS shuffling that facilitates the evolution of genes. PMID- 9973611 TI - FBI-1, a factor that binds to the HIV-1 inducer of short transcripts (IST), is a POZ domain protein. AB - The HIV-1 promoter directs the synthesis of two classes of transcripts, short, non-polyadenylated transcripts and full-length, polyadenylated transcripts. The synthesis of short transcripts is activated by a bipartite DNA element, the inducer of short transcripts or IST, located downstream of the HIV-1 transcriptional start site, while the synthesis of full-length transcripts is activated by the viral activator Tat. Tat binds to the RNA element TAR, which is encoded largely between the two IST half-elements. Upon activation by Tat, the synthesis of short RNAs is repressed. We have previously purified a factor called FBI-1 (for factor that binds to IST) whose binding to wild-type and mutated ISTs correlated well with the abilities of these ISTs to direct the synthesis of short transcripts. Here, we report the cloning of cDNAs encoding FBI-1. FBI-1 contains a POZ domain at its N-terminus and four Kruppel-type zinc fingers at its C terminus. The C-terminus is sufficient for specific binding, and FBI-1 can form homomers through its POZ domain and, in vivo, through its zinc finger domain as well. In addition, FBI-1 associates with Tat, suggesting that repression of the short transcripts by Tat may be mediated through interactions between the two factors. PMID- 9973612 TI - A gene encoding an intestinal-enriched member of the Kruppel-like factor family expressed in intestinal epithelial cells. AB - The Kruppel-like factors make up a multigene family of transcription factors that have discrete patterns of expression, implying they play important biological roles in the tissues in which they are expressed. We have identified and characterized the cDNA for a novel murine transcription factor that is an additional member of the Kruppel-like family of transcription factors, named intestinal-enriched Kruppel-like factor (IKLF). This gene appears to be a homolog of the human BTEB-2 gene, although it exhibits a different pattern of tissue expression and the translated product is larger. IKLF is expressed in a limited number of tissues; the highest levels of IKLF expression are found in the digestive tract. IKLF shows temporal changes in expression during embryogenesis indicating that this gene is developmentally regulated. In addition, IKLF expression is limited to the epithelial lining of the intestine and is localized primarily to the base of the crypts in the adult intestine. The IKLF cDNA encodes for a 446 amino acid protein and is able to transactivate by binding specific DNA elements that are also recognized by other members of the Kruppel-like family. In addition, mutations in the activation domain attenuate the ability of this protein to function as a transcription factor. Collectively, these findings show that we have identified a transcription factor that is expressed predominantly in the epithelial crypt cells of the gastrointestinal tract and is a member of the Kruppel-like family of transcription factors. PMID- 9973613 TI - An allylic/acyclic adenosine nucleoside triphosphate for termination of DNA synthesis by DNA template-dependent polymerases. AB - An allylic adenosine triphosphate analog (AATP) was tested as a substrate for commercially available DNA polymerases. All but one of the enzymes assayed incorporated AATP opposite thymidine (T) with concomitant termination of the elongation reaction. A concentration of only 1 microM was sufficient for complete termination of the polymerization reaction for a short template mediated by Ampli Taq DNA polymerase FS (Taq FS). This result suggests that AATP could be used as a 2',3'-dideoxyadenosine-5'-triphosphate (ddA) surrogate. Kinetics of incorporation revealed that AATP was 48 times less efficiently incorporated than ddA. Furthermore, AATP was used in dye-primer sequencing as a substitute for ddA. PMID- 9973614 TI - Escherichia coli RuvBL268S: a mutant RuvB protein that exhibits wild-type activities in vitro but confers a UV-sensitive ruv phenotype in vivo. AB - The RuvABC proteins of Escherichia coli process recombination intermediates during genetic recombination and DNA repair. RuvA and RuvB promote branch migration of Holliday junctions, a process that extends heteroduplex DNA. Together with RuvC, they form a RuvABC complex capable of Holliday junction resolution. Branch migration by RuvAB is mediated by RuvB, a hexameric ring protein that acts as an ATP-driven molecular pump. To gain insight into the mechanism of branch migration, random mutations were introduced into the ruvB gene by PCR and a collection of mutant alleles were obtained. Mutation of leucine 268 to serine resulted in a severe UV-sensitive phenotype, characteristic of a ruv defect. Here, we report a biochemical analysis of the mutant protein RuvBL268S. Unexpectedly, the purified protein is fully active in vitro with regard to its ATPase, DNA binding and DNA unwinding activities. It also promotes efficient branch migration in combination with RuvA, and forms functional RuvABC Holliday junction resolvase complexes. These results indicate that RuvB may perform some additional, and as yet undefined, function that is necessary for cell survival after UV-irradiation. PMID- 9973615 TI - The exosome subunit Rrp43p is required for the efficient maturation of 5.8S, 18S and 25S rRNA. AB - The Saccharomyces cerevisiae protein Rrp43p co-purifies with four other 3'-->5' exoribonucleases in a complex that has been termed the exosome. Rrp43p itself is similar to prokaryotic RNase PH. Individual exosome subunits have been implicated in the 3' maturation of the 5.8S rRNA found in 60S ribosomes and the 3' degradation of mRNAs. However, instead of being deficient in 60S ribosomes, Rrp43p-depleted cells were deficient in 40S ribosomes. Pulse-chase and steady state northern analyses of pre-RNA and rRNA levels revealed a significant delay in the synthesis of both 25S and 18S rRNAs, accompanied by the stable accumulation of 35S and 27S pre-rRNAs and the under-accumulation of 20S pre-rRNA. In addition, Rrp43p-depleted cells accumulated a 23S aberrant pre-rRNA and a fragment excised from the 5' ETS. Therefore, in addition to the maturation of 5.8S rRNA, Rrp43p is required for the maturation 18S and 25S rRNA. PMID- 9973616 TI - A single point mutation in the yeast TRP4 gene affects efficiency of mRNA 3' end processing and alters selection of the poly(A) site. AB - The yeast TRP4 mRNA 3' end formation element is a bidirectional element which functions in both orien-tations in an artificial in vivo test system. In this study, the role of 3' end formation was analysed in the context of the entire TRP4 gene. The 3' untranslated region (3'UTR) of TRP4 was altered and changes were analysed for their influence on TRP4 gene expression. The 3'UTR in reverse orientation was fully functional and did not affect TRP4 gene expression. Exchanging the TRP4 3'UTR by the bidirectional ARO4 or the unidirectional GCN4 3' end formation element allowed efficient gene expression. Deletion of the entire TRP4 3'UTR resulted in 70% reduction of TRP4 mRNA and 50% reduced specific Trp4 enzyme activity in comparison to wild-type. A single point mutation within the TRP4 3'UTR caused the same effect on gene expression. This point mutation did not only affect the efficiency of 3' end formation, but also produced new poly(A) sites which were situated upstream of the wild-type poly(A) sites. Therefore this sequence motif in the TRP4 3'UTR acts simultaneously as both an efficiency and positioning element. PMID- 9973617 TI - Gene replacement with linear DNA in electroporated wild-type Escherichia coli. AB - Gene replacement using linear double-stranded DNA fragments in wild-type Escherichia coli transformation is generally inefficient due to exonucleolytic degradation of incoming DNA. Recombination-proficient strains, in which the exonucleolytic activity of RecBCD is inactivated, have been used as transformation recipients to overcome this difficulty. Here we report that gene replacements using linear double-stranded donor DNA can be achieved in wild-type E.coli if electrocompetent cells are used. Using a plasmid target, we obtained 10(2)-10(3) gene replacement events/microgram linear DNA. Using an independent chromosomal target, approximately 60 gene replacement events/microgram linear DNA were obtained. The presence of Chi sites on the linear DNA, which are known to block DNA degradation and stimulate recombination in E.coli, had no effect on gene replacement efficiency in either case. RecBCD-mediated exonucleolytic activity was found to be diminished in electroporated cells. Electrotransformation thus provides a simple way to perform gene replacements in many E.coli strains. PMID- 9973618 TI - MicroSAGE: a modified procedure for serial analysis of gene expression in limited amounts of tissue. AB - Serial Analysis of Gene Expression (SAGE) is a powerful expression profiling method, allowing the analysis of the expression of thousands of transcripts simultaneously. A disadvantage of the method, however, is the relatively high amount of input RNA required. Consequently, SAGE cannot be used for the generation of expression profiles when RNA is limited, i.e. in small biological samples such as tissue biopsies or microdissected material. Here we describe a modification of SAGE, named microSAGE, which requires 500- to 5000-fold less starting material. Compared with SAGE, microSAGE is simplified due to incorporation of a 'single-tube' procedure for all steps from RNA isolation to tag release. Furthermore, a limited number of additional PCR cycles are performed. Using microSAGE gene expression profiles can be obtained from minute quantities of tissue such as a single hippocampal punch from a rat brain slice of 325 micrometers thickness, estimated to contain, at most, 10(5) cells. This method opens up a multitude of new possibilities for the application of SAGE, for example the characterization of expression profiles in tissue biopsies, tumor metastases or in other cases where tissue is scarce and the generation of region specific expression profiles of complex heterogeneous tissues. PMID- 9973619 TI - Transfer RNA modification enzymes from Pyrococcus furiosus: detection of the enzymatic activities in vitro. AB - The modification patterns of in vitro transcripts of two yeast Saccharomyces cerevisiae tRNAs (tRNAPheand tRNAAsp) and one archaeal Haloferax volcanii tRNA (tRNAIle) were investigated in the cell-free extract of Pyrococcus furiosus supplemented with S -adenosyl-l-methionine (AdoMet). The results indicate that the enzymatic formation of 11 distinct modified nucleotides corresponding to 12 enzymatic activities can be detected in vitro. They correspond to the formation of pseudouridines (Psi) at positions 39 and 55, 2' -O- ribose methylations at positions 6 (Am) and 56 (Cm), base methylations at positions 10 (m2G), 26 (m22G), 37 (m1G), 49 (m5C), 54 (m5U) and 58 (m1A) and both the deamination and methylation of adenosine into m1I at position 57. Most of the detected modified nucleotides are common modifications found in other phylogenetic groups, while Am6, Cm56and m1I57are specific modifications found exclusively in Archaea. It is also shown that the enzymatic formation of m5C49, m5U54, Psi55and m1I57does not depend on the three-dimensional architecture of the tRNA substrate, since these modi-fications also occur in fragmented tRNAs as substrate. PMID- 9973620 TI - Novel non-isotopic detection of MutY enzyme-recognized mismatches in DNA via ultrasensitive detection of aldehydes. AB - A highly sensitive method to detect traces of aldehyde-containing apurinic/apyrimidinic (AP) sites in nucleic acids has been developed. Based on this method, a novel approach to detect DNA base mismatches recognized by the mismatch repair glycosylase MutY is demonstrated. Open chain aldehydes generated in nucleic acids due to spontaneous depurination, DNA damage or base excision of mismatched adenine by MutY are covalently trapped by a new linker molecule [fluorescent aldehyde-reactive probe (FARP), a fluorescein-conjugated hydroxylamine derivative]. DNA containing AP sites is FARP-trapped, biotinylated and immobilized onto neutravidin-coated microplates. The number of FARP-trapped aldehydes is then determined via chemiluminescence using a cooled ICCD camera. AP sites induced in plasmid or genomic calf thymus DNA via mild depurination or by simple incubation at physiological conditions (pH 7, 37 degreesC) presented a linear increase in chemiluminescence signal with time. The procedure developed, from a starting DNA material of approximately 100 ng, allows detection of attomole level (10(-18) mol) AP sites, or 1 AP site/2 x 10(7) bases, and extends by 1-2 orders of magnitude the current limit in AP site detection. In order to detect MutY-recognized mismatches, nucleic acids are first treated with 5 mM hydroxylamine to remove traces of spontaneous aldehydes. Following MutY treatment and FARP-labeling, oligonucleotides engineered to have a centrally located A/G mismatch demonstrate a strong chemiluminescence signal. Similarly, single stranded M13 DNA that forms mismatches via self-complementation (average of 3 mismatches over 7429 bases) and treated with MutY yields a signal approximately 100-fold above background. No signal was detected when DNA without mismatches was used. The current development allows sensitive, non-isotopic, high throughput screening of diverse nucleic acids for AP sites and mismatches in a microplate based format. PMID- 9973621 TI - Targeted gene repair directed by the chimeric RNA/DNA oligonucleotide in a mammalian cell-free extract. AB - Chimeric oligonucleotides consisting of RNA and DNA residues have been shown to catalyze site-directed genetic alteration in mammalian cells both in vitro and in vivo. Since the frequency of these events appears to be logs higher than the rates of gene targeting, a process involving homologous recombination, we developed a system to study the mechanisms of chimera-directed gene conversion. Using a mammalian cell-free extract and a genetic readout in Escherichia coli, we find that point mutations and single base deletions can be corrected at frequencies of approximately 0.1% and 0.005%, respectively. The reaction depends on an accurately designed chimera and the presence of functional hMSH2 protein. The results of genetic and biochemical studies reported herein suggest that the process of mismatch repair functions in site-directed gene correction. PMID- 9973622 TI - Cloning and characterization of the p42 subunit of mammalian translation initiation factor 3 (eIF3): demonstration that eIF3 interacts with eIF5 in mammalian cells. AB - Eukaryotic translation initiation factor 3 (eIF3) is a large multisubunit protein complex that plays an essential role in the binding of the initiator methionyl tRNA and mRNA to the 40S ribosomal subunit to form the 40S initiation complex. cDNAs encoding all the subunits of mammalian eIF3 except the p42 subunit have been cloned in several laboratories. Here we report the cloning and characterization of a human cDNA encoding the p42 subunit of mammalian eIF3. The open reading frame of the cDNA, which encodes a protein of 320 amino acids (calculated Mr35 614) has been expressed in Escherichia coli and the recombinant protein has been purified to homogeneity. The purified protein binds RNA in agreement with the presence of a putative RNA binding motif in the deduced amino acid sequence. The protein shows 33% identity and 53% similarity with the Tif35p subunit (YDR 429C) of yeast eIF3. Transfection experiments demonstrated that polyhistidine-tagged p42 protein, transiently expressed in human U20S cells, was incorporated into endogenous eIF3. Furthermore, eIF3 isolated from transfected cell lysates contains bound eIF5 indicating that a specific physical interaction between eIF5 and eIF3 may play an important role in the function of eIF5 during translation initiation in eukaryotic cells. PMID- 9973623 TI - Heat shock of HeLa cells inactivates a nuclear protein phosphatase specific for dephosphorylation of the C-terminal domain of RNA polymerase II. AB - Reversible phosphorylation of the C-terminal domain (CTD) of the largest RNA polymerase II (RNAP II) subunit plays a key role in gene expression. Stresses such as heat shock result in marked changes in CTD phosphorylation as well as in major alterations in gene expression. CTD kinases and CTD phosphatase(s) contribute in mediating differential CTD phosphory-lation. We now report that heat shock of HeLa cells at temperatures as mild as 41 degreesC results in a decrease in CTD phosphatase activity in cell extracts. The obser-vation that this CTD phosphatase interacts with the RAP74 subunit of the general transcription factor TFIIF suggests that it corresponds to the previously charac-terized major CTD phosphatase. This conclusion is also supported by the finding that the distribution of the 150 kDa subunit of CTD phosphatase in cells is altered by heat shock. Although CTD phosphatase is found predominantly in low salt extracts in unstressed cells, immunofluorescence microscopy indicates that its intracellular localization is nuclear. The decrease in CTD phosphatase activity correlates with a decrease in amount of 150 kDa phosphatase subunit in the extracts. During heat shock, CTD phosphatase switches to an insoluble form which remains aggregated to the nuclear matrix fraction. In contrast, heat shock did not result in a redistribution of RAP74, indicating that not all nuclear proteins aggregate under these conditions. Accordingly, the heat-inactivation of both the CTD phosphatase and the TFIIH-associated CTD kinase might contribute to the selective synthesis of heat-shock mRNAs. PMID- 9973624 TI - Increased specificity of reverse transcription priming by trehalose and oligo blockers allows high-efficiency window separation of mRNA display. AB - We have developed a method for high-efficiency window separation of cDNA display by increasing the specificity of priming in reverse transcription. In the conventional method, two-base anchored oligo(dT) primers (5'dT16VN3', where N is any base and V is G, A or C) are used to make windows for the display of transcripts. However, reverse transcriptase often extends misprimed oligonucleotides. To avoid mispriming from dT16VN primers, we have developed two new technologies. One is higher temperature priming with reverse transcriptase thermoactivated by the disaccharide trehalose. The other is the use of competitive oligonucleotide blockers that hybridize to the non-selectively primed mRNAs, preventing the mispriming from the VN site. These methods were combined to improve restriction landmark cDNA scanning (RLCS), resulting in the elimination of the redundant signals that appear in different windows. This was achieved by the increased specificity of initiation of reverse trans-cription from the beginning of poly(A) sites. This method paves the way for the precise visualization of transcripts to allow expression profiles in individual tissues and at each developmental stage to be understood. PMID- 9973625 TI - Binding of the glucose-dependent Mig1p repressor to the GAL1 and GAL4 promoters in vivo: regulationby glucose and chromatin structure. AB - Binding of the MIG1 repressor to the glucose-repressible GAL1 and GAL4 promoters was analyzed in vivo by cyclobutane dimer footprinting in two yeast strains that show different glucose repression responses. Mig1p binding to the two promoters in both strains was glucose-induced. In cells subject to rapid and stringent glucose repression (S288c), long-term Mig1p binding in glucose-grown cells was inhibited by the formation of a competing chromatin structure. Under conditions where glucose repression was only partially effective (gal80 - or low glucose), the chromatin structure did not form and long-term Mig1p binding was observed The same long-term binding of Mig1p was seen in cells of a different strain (W303A) that shows only partial glucose repression of the GAL1 promoter. We conclude from these experiments that Mig1p binding to glucose-repressed promoters is glucose dependent but transient. We suggest that Mig1p functions at an early step in repression, but is not required to maintain the repressed state. PMID- 9973626 TI - The DNA-binding specificity of SOX9 and other SOX proteins. AB - SOX (SRY-related HMG box) proteins are transcription factors that have critical roles in the regulation of numerous developmental processes. They share at least 50% homology in their HMG domains, which bind the DNA element AACAAT. How different SOX proteins achieve specific regulation of target genes is not known. We determined the DNA-binding specificity of SOX9 using a random oligonucleotide selection assay. The optimal SOX9 binding sequence, AGAACAATGG, contained a core DNA-binding element AACAAT, flanked by 5' AG and 3' GG nucleotides. The specific interaction between SOX9 and AGAACAATGG was confirmed by mobility shift assays, DNA competition and dissociation studies. The 5' AG and 3' GG flanking nucleotides enhance binding by SOX9 HMG domain, but not by the HMG domain of another SOX factor, SRY. For SRY, different 5' and 3' flanking nucleotides are preferred. Our studies support the notion that SOX proteins achieve DNA sequence specificity through subtle preferences for flanking nucleotides and that this is likely to be dictated by signature amino acids in their HMG domains. Furthermore, the related HMG domains of SOX9 and Sox17 have similar optimal binding sites that differ from those of SRY and Sox5, suggesting that SOX factors may co-evolve with their DNA targets to achieve specificity. PMID- 9973627 TI - Repair of 8-oxoguanine in DNA is deficient in Cockayne syndrome group B cells. AB - The incision of the 8-oxoguanine in DNA by normal and Cockayne Syndrome (CS) cell extracts has been investigated. The incision in extracts derived from CS cells was approximately 50% of the incision level compared with extracts prepared from normal cells. In contrast, the incision rate of uracil and thymine glycol was not defective in CS cells. The deficiency in 8-oxoguanine incision was also demonstrated in a CS family. Whereas the proband had markedly less incision compared with the normal siblings, the parents had intermediate levels. The low level of 8-oxoguanine-DNA glycosylase in CS extracts correlates with the reduced expression of the 8-oxoguanine-DNA glycosylase gene (hOGG1) in CS cells. Both the levels of expression of the hOGG1 gene and the incision of 8-oxoguanine in DNAincreased markedly after transfection of CS-B cells with the CSB gene. We suggest that the CSB mutation leads to deficient transcription of the hOGG1 gene and thus to deficient repair of 8-oxoguanine in DNA. PMID- 9973628 TI - Probing the environment of nascent RNA in Escherichia coli transcription elongation complexes utilizing a new fluorescent ribonucleotide analog. AB - We report the synthesis and characterization of 5-thioacetamidofluorescein uridine 5'-triphosphate (5-SF-UTP), and its application to the characterization of the environment of the nascent RNA during trans-cription. This analog specifically replaced UTP as a transcription substrate for Escherichia coli and T7 RNA polymerases, and yeast RNA polymerase III. Escherichia coli transcription complexes containing analog incorporated at only position +21 of the RNA were prepared. The RNA was then elongated in the absence of analog, moving the fluorescent group further away from the enzyme active site, and the fluorescence polarization was measured. Analog positioned near the 3' end of the transcript exhibited significantly increased polarization relative to that of free probe, consistent with the constrained environment of the RNA in the DNA-RNA hybrid. Analog positioned 14 nucleotides from the 3' end exhibited significantly decreased polarization relative to that at the 3' end of the RNA, but only slightly above that of free RNA, suggesting that the probe was on the solvent exposed surface of the polymerase. Molecular modeling of these analog-substituted RNAs produced structures consistent with the experimental data. The excellent substrate properties of this analog make it useful for the characterization of the environment of RNA not only during transcription and translation, but in any type of ribonucleoprotein complex. PMID- 9973629 TI - Coordination of kRNA editing and polyadenylation in Trypanosoma brucei mitochondria: complete editing is not required for long poly(A) tract addition. AB - Mitochondrial RNAs in Trypanosoma brucei are post-transcriptionally modified by the addition and deletion of uridylate residues in a process called kRNA editing. Unedited, partially edited and fully edited RNAs exist in the steady-state RNA population. Previous experiments have demonstrated that T.brucei mitochondrial RNAs contain both short (approximately 20 nt) and long (120-200 nt) poly(A) tracts. However, it is unknown exactly what poly(A) tract lengths are present on unedited, partially edited and fully edited RNAs. To gain insight into the role of the poly(A) tract in T.brucei mitochondria, ribosomal protein S12 (RPS12) RNAs with short and long poly(A) tracts were purified by hybrid selection and analyzed by RT-PCR and DNA sequencing. Unedited RPS12 RNAs were found almost exclusively in populations with short poly(A) tracts. Both partially and fully edited RPS12 RNAs were found in populations with short and long poly(A) tracts. Therefore, there is a correlation between the presence of editing and the presence of the long poly(A) tract. Since a proportion of partially edited RPS12 RNAs contain long poly(A) tracts, it is unlikely that the long poly(A) tract is the sole signal for translation. Other implications for the role of polyadenylation in mitochondrial gene regulation are discussed. PMID- 9973630 TI - Mammalian polyadenylation sites: implications for differential display. AB - Differential display relies on a series of anchored primers to divide the total mRNA population into subsets of roughly equal size. However, this will only occur if the dinucleotide targeted by the anchor region of the anchored primers has a random frequency distribution [i.e. each of the 12 possible dinucleotides preceding the poly(A) tail occur with the same frequency]. Previous reports have suggested that this is not the case and that the frequency distribution of the targeted dinucleotide can vary as much as 10-fold. In an analysis of several hundred unrelated mammalian mRNA sequences, we confirmed that the frequency of this particular dinucleotide does vary, although <3-fold. Of equal importance, however, we found that the number of bands displayed with each of the respective anchored primers was not affected by these variations in dinucleotide frequency, suggesting that anchored primer promiscuity permits mispriming during the reverse transcription stage of differential display. Close examination of this issue suggested that both mispriming at the anchor region and internal mispriming are common in differential display reverse transcription and implies that repetitive sampling occurs exten-sively in differential display. Thus, reverse transcriptase mispriming may considerably reduce the efficiency of differential display. PMID- 9973631 TI - Structure of influenza virus panhandle RNA studied by NMR spectroscopy and molecular modeling. AB - The structure of a 34 nucleotide RNA molecule in solution, which contains the conserved panhandle sequences, was determined by NMR spectroscopy and molecular modeling. The partially double-strandedpanhandle structure of the influenza virus RNA serves to regulate initiation and termination of viral transcription as well as polyadenylation. The panhandle RNA consists of internal loop flanked by short helices. The nucleotides at or near the internal loop are crucial for polymerase binding and transcriptional activity. They show more flexible conformational character than the Watson-Crick base-paired region, especially for the backbone torsion angles of alpha, gamma and delta. Although residues A10 and A12 are stacked in the helix, the phosphodiester backbones are distorted. Residues A12, A13 and G25 show dynamic sugar conformations and the backbone conformations of these nucleotides are flexible. This backbone conformation and its associated flexibility may be important for protein-RNA interactions as well as base specific interactions. PMID- 9973632 TI - Unusual nucleotide conformations in GNRA and UNCG type tetraloop hairpins: evidence from Raman markers assignments. AB - High resolution NMR data on UNCG and GNRA tetraloops (where N is any of the four nucleotides and R is a purine) have shown that they contain ribonucleosides with unusual 2'-endo/anti and 3'-endo/syn conformations, in addition to the 3' endo/anti ones which are regularly encountered in RNA chains. In the current study, Raman spectroscopy has been used to probe these nucleoside conformations and follow the order (hairpin) to disorder (random chain) structural transitions in aqueous phase in the 5-80 degreesC temperature range. Spectral evolution of GCAA and GAAA tetraloops, as formed in very short hairpins with only three G.C base pairs in their stems (T m >60 degreesC), are reported and compared with those previously published on UUCG and UACG tetraloops, for which the syn orientation of the terminal guanine as well as the 2'-endo/anti conformation of the third rC residue have been confirmed by means of vibrational marker bands. Raman data obtained as a function of temperature show that the first uracil in the UUCG tetraloop is stacked and the two middle residues (rU and rC) are in the 2'-endo/anti conformation, in agreement with the previously published NMR results. As far as the new data concerning the GNRA type tetraloops are concerned, they lead us to conclude that: (i) in both cases (GCAA and GAAA tetraloops) the adenine bases are stacked; (ii) the second rC residue in the GCAA tetraloop has a 3'-endo/anti conformation; (iii) the sugar pucker associated with the third rA residue in both tetraloops possibly undergoes a 3'-endo/2'-endo interconversion as predicted by NMR results; (iv) the stem adopts a regular A form structure; (v) all other nucleosides of these two GNRA tetraloops possess the usual 3'-endo/anti conformation. PMID- 9973633 TI - Manganese citrate improves base-calling accuracy in DNA sequencing reactions using rhodamine-based fluorescent dye-terminators. AB - While dideoxy-terminators labeled with rhodamine-based fluorescent dyes provide the most versatile method of automated DNA sequencing, variation in peak heights reduces base-calling accuracy. We describe a simple approach that uses additions of a manganese salt and the metal buffer sodium citrate (MnCit) to overcome this limitation. This modification reduces peak height variability >2-fold and significantly increases the number of accurately read bases in DNA sequences. PMID- 9973634 TI - Neural substrate for motor control of feeding in amphibians. AB - Descending pathways to premotor/motor centers and their cell groups of origin were studied by means of retrograde biocytin tracing experiments in the frog Discoglossus pictus and the plethodontid salamander Plethodon jordani, which differ remarkably in the structure and function of their feeding apparatus and their feeding strategy. Labeled neurons were found in 30 major cell groups located in the telencephalon, diencephalon, synencephalon, mesencephalon and rhombencephalon. The number and distribution of nuclei are very similar in both species. Furthermore, the descending pathways of these groups of neurons take the same courses inside the medulla oblongata. Axons of most nuclei descend either in the ventromedial or ventrolateral medulla oblongata, and it is concluded that the spatial arrangement of pathways is identical in the species studied. Bilateral electrical stimulation of the optic tectum of the plethodontid salamander Hydromantes italicus elicited strong discharges of short latencies in the hypoglossal nerve. In most hypoglossal motor neurons, excitatory postsynaptic potentials (EPSPs) of short latencies followed paired shocks applied at intervals as short as 3 ms, but showed temporal and spatial facilitation, suggesting that the EPSPs include mono- as well as polysynaptic components. In the ventral white matter, orthodromic single units were found that are candidates for excitatory reticular interneurons. These properties of tectal descending pathways in salamanders strongly differ from those found in toads. Differences in feeding behavior and its control by the premotor/motor networks between the species investigated do not appear to result from anatomically altered input or from a different organization of descending pathways to these premotor/motor centers, but rather from differences in local properties of reticular premotor networks as well as from different effects of neuromodulatory systems. PMID- 9973635 TI - Complex movement patterns: modifiability and constraints. AB - Most behaviours involve complex morphological systems and vice versa morphological systems are used by the organism in many different ways. During evolution and ontogeny changes in kinematics and function of skeletal and muscular systems must be coordinated with changes in their neural control. Neuromotor patterns are sometimes believed to be conserved in evolution, leading to diversification at the level of musculoskeletal design. Vertebrate motor patterns used in feeding are reviewed to examine this hypothesis. Stereotyped behaviour is not necessarily the result of phylogenetic constraints but may also result from the functional demands imposed by the mechanics of the jaw apparatus and the nature of the task performed. Sensory feedback and descending control not only contribute to 'online' control of movement but also shape the development of motor patterns and learning behaviour and indicate a potentially large flexibility. The neural and sensory apparatus that produces this flexibility will be subject to evolutionary modification. In the absence of a demand for flexibility motor patterns may become stereotyped in some species, while they are very flexible in others. To the extent that morphological systems perform independent movements during different behaviours, separate basic motor patterns may be required, which may be coordinated in different ways. PMID- 9973636 TI - The neural substrate for 'learned' and 'nonlearned' activities in birds: a discussion of the organization of bulbar reticular premotor systems with side lights on the mammalian situation. AB - The reticular formation of the brainstem contains premotor systems for various musculomotor systems. In this paper, the bulbar premotor systems for jaw and tongue movements, head and neck movements, locomotion, and respiration and vocalization in birds are reviewed and compared to premotor systems in mammals. Roughly, the bulbar reticular formation can be subdivided in three longitudinal zones: a dorsolateral (RPcdl) and a ventromedial (RPcvm) parvocellular zone and a gigantocellular zone (RGc). RPcdl contains premotor neurons for the jaw and neck system, RPcvm for the jaw, tongue and neck system, and RGc for the tongue and locomotory system. RPcdl receives input from the descending sensory trigeminal system, parts of RPcvm and RGc from vestibular nuclei, whereas the tectum has a projection to the contralateral RGc. RPcdl and RPcvm receive substantial telencephalic input through the occipitomesencephalic tract. The bulbar part of the respiratory system consists of a series of cell groups in the ventrolateral reticular formation and has connections with motor centers of the vocalization system. The similarities and differences between the avian and mammalian situation are discussed. Musculomotor systems participate in various activities. It is argued that a premotor system should possess sufficient flexibility to control the participation of a motor system in the different activities. This flexibility may permit the occurrence of learning processes in terms of refining basically existing motor patterns. The emergence of new and more complex motor patterns as in vocalization requires the involvement of hierarchically higher brain centers. PMID- 9973637 TI - Complete blood counts from umbilical cords of healthy term newborns by two automated cytometers. AB - Complete blood counts (CBC) of umbilical cord blood from 123 healthy term newborns were simultaneously performed with two different cytometers using laser as a light source. Medians (95% range) were: WBC 14.2 (7.8-24.3) x 10(9)/l, platelets 265 (174-363) x 10(9)/l, Hb 15.7 (12.5-18.2) g/dl, RBC 4.6 (3.9-5.5) x 10(12)/l, MCV 106 (95-113) fl, PCV 0.49 (0.40-0.56), and MCH 33.8 (30.3-36.4) pg. Reticulocytes were 149 (95-212) x 10(9)/l or 3.3 (2.0-4.7)%; erythroblasts 5 (0 24) per 100 WBC or 0.53 (0.00-3.20) x 10(9)/l. The counters agreed well except for MCHC. WBC counts showed the smallest difference irrespective of erythroblast number; platelets showed the largest difference. The lower limit for normal Hb should be fixed at 12.5 g/dl for the adequate diagnosis of anaemia from cord blood of term newborns. PMID- 9973638 TI - A human myeloid cell line producing stem cell growth factor, KPB-M15, secretes another growth factor active on murine hematopoietic progenitor cells. AB - Human stem cell growth factor (SCGF) produced by a myeloid cell line, KPB-M15, exhibits species-specific hematopoietic activities. However, KPB-M15-conditioned medium induced colony formation of mouse bone marrow cells. KPB-M15-derived colony-stimulating activity (CSA) was purified through Butyl-Toyopearl 650c and Cu2+ chelating-Sepharose 6B chromatography. TSK-G3000SW gel filtration of the purified preparation presented 3 distinct peaks around Vo, 150 kD and 85 kD. Gel fractions extracted from SDS-PAGE had macrophage colony-stimulating factor (M CSF)-specific amino acid sequences. PCR, Northern hybridization and ELISA demonstrated that KPB-M15 cells secreted a significant amount of M-CSF and IL-6. Anti-M-CSF but not anti-IL-6 antibody abrogated CSA in KPB-M15-CM. IL-6 hardly synergized with M-CSF to enhance colony formation. Collectively, M-CSF is a sole CSA for murine hematopoietic progenitor cells in KPB-M15-CM. This is the first report of a human myeloid cell line, KPB-M15, constitutively producing M-CSF in addition to SCGF and IL-6. It can be useful in investigating the mechanism of production of M-CSF. PMID- 9973639 TI - Expression of the Rh-related glycoprotein (Rh50). AB - The Rh50 glycoprotein is suspected of being involved in Rh antigen expression. We prepared Rh50 cDNA from a human bone marrow library by polymerase chain reaction and then subcloned this cDNA into various vectors. The vector containing Rh50 cDNA produced a 30-kDa nonglycosylated form of Rh50 in a rabbit reticulocyte lysate system and produced partially glycosylated Rh50 (32 kDa) when microsomes were added to the system. COS-1 cells transiently transfected with the vector containing Rh50 cDNA produced partially glycosylated Rh50 (32 kDa) recognized by a Rh50-specific antibody. Surface expression of Rh50 in K562 cells was also detected by flow cytometry using mouse monoclonal antibody (2D10) specific to Rh50. Partially glycosylated Rh50 (32 kDa) was again isolated from the lysates of K562 cells metabolically labeled with [35S]-methionine or [3H]-mannose using anti Rh50 antisera. These systems (K562 and COS-1 cells) should prove useful for studying the transport of Rh proteins within the cell and the necessary components needed for Rh antigenicity at the cell surface. PMID- 9973640 TI - In vivo administration of granulocyte colony-stimulating factor increases the surface expression of sialyl-Lewis(x) on neutrophils in healthy volunteers. AB - We examined the in vivo effect of granulocyte colony-stimulating factor (G-CSF) on the surface expression of putative counterligands for endothelial selectins on neutrophils in healthy volunteers. G-CSF (50 microg/m2/day) was administered subcutaneously to 5 healthy volunteers for 4 days. The expression of surface antigens on neutrophils was determined by flow cytometry and monoclonal antibodies. G-CSF administration increased the number of leukocytes, mainly of neutrophils, which was associated with an increase in the expression of the high affinity Fc receptor for IgG (FcRI, CD64) and CD14 on neutrophils. G-CSF administration decreased the surface expression of L-selectin on neutrophils, whereas it increased the expression of sialyl-Lewisx but not Lewisx on neutrophils. These findings suggest that G-CSF participates in the neutrophil endothelial cell interactions in vivo by modulating the expression of adhesion molecules and ligands for endothelial selectins on neutrophils. PMID- 9973641 TI - A case of atypical chronic myeloid leukemia regarded as MDS with myeloproliferative features. AB - We report a case of atypical chronic myeloid leukemia (aCML) who showed marked neutrophilia without dysplastic features, basophilia or monocytosis. These findings diverged somewhat from the FAB criteria for aCML. The patient's erythroid cells and megakaryocytes were dysplastic. His marrow cells formed no spontaneous colonies, as shown by cell culture. The cells formed many small-sized neutrophil colonies with G-CSF stimulation. Interestingly, they formed mainly neutrophil colonies with GM-CSF stimulation. These findings were different from those of chronic myelomonocytic leukemia cells and chronic granulocytic leukemia cells. This aCML case showed the cytological features of myelodysplastic syndrome. PMID- 9973642 TI - Human parvovirus B19 capsid antigen in granulocytes in parvovirus-B19-induced pancytopenia after bone marrow transplantation. AB - A patient with refractory anemia with an excess of blasts in transformation developed pancytopenia and a concurrent interstitial pneumonia 110 days after allogeneic bone marrow transplantation. Bone marrow examination showed 0.4% giant proerythroblasts and 86.2% granulocytes, some of them large with a bizarre configuration and the others of normal size. Serum folate level was found low, 0.6 ng/ml. Immunocytochemistry with a B19-specific monoclonal antibody MAB8292 revealed B19 capsid antigen only in erythroblasts and large, bizarre granulocytes, but not in granulocytes of normal size. In situ hybridization of bone marrow cells using digoxigenin-labeled DNA probes detecting parvovirus B19 also demonstrated positive signals in 8.5% of marrow cells. Parvovirus B19 DNA was isolated from the serum and the bronchoalveolar lavage fluid of this patient by the polymerase chain reaction. These findings suggest that neutropenia may be caused by an involvement with parvovirus B19 though a deficiency of folic acid may have in part contributed to the genesis of neutropenia in the patient. The relevance of parvovirus B19 to the interstitial pneumonia remains unclear. PMID- 9973643 TI - Band 3 Tokyo: Thr837-->Ala837 substitution in erythrocyte band 3 protein associated with spherocytic hemolysis. AB - We report a case of spherocytosis associated with erythrocyte band 3 deficiency. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of erythrocyte membrane proteins showed that the patient's band 3 was reduced to about 80% of the control level. Molecular analysis revealed that this quantitative alteration was accompanied by a novel base change at codon 837 (ACG-->GCG) of the AE1 gene, resulting in substitution of alanine for threonine. In bone marrow mononuclear cells, both mutant and wild-type mRNA were comparably detected, suggesting that this mutation interfered with band 3 processing or assembly, leading to impaired accumulation of mutant band 3 in the plasma membrane. PMID- 9973644 TI - Thrombotic thrombocytopenic purpura complicating chronic myelogenous leukemia treated with interferon-alpha. A report of two successfully treated patients. AB - Two patients with chronic myelogenous leukemia are described in whom thrombotic thrombocytopenic purpura (TTP) developed following treatment by interferon-alpha. In one of the patients, a lymphoblastic transformation was diagnosed concomitantly. Prompt institution of plasmapheresis, steroids and vincristine resulted in complete resolution. In the hitherto reported case of TTP complicating interferon-alpha treated chronic myelogenous leukemia, the course was fatal. PMID- 9973645 TI - Pure red cell aplasia associated to clonal CD8+ T-cell large granular lymphocytosis: dependence on cyclosporin A therapy. AB - This case report details a single patient with pure red cell aplasia (PRCA) associated with clonal CD3+, TCRalphabeta+, TCR-Vbeta8+, CD8+, CD57+ large granular lymphocytosis whose anaemia did not respond to conventional immunosuppressive therapy but did respond to cyclosporin A (CsA). The patient has become dependent on CsA for 7 years in order to control anaemia due to associated PRCA. PMID- 9973646 TI - Mononeuropathy multiplex in the course of idiopathic thrombocytopenic purpura. A case report. AB - We report the simultaneous occurrence of idiopathic thrombocytopenic purpura and mononeuropathy multiplex in a 21-year-old man. Electromyographic study revealed various axonal degenerative alterations in the right and left peroneal and right tibial nerves. PMID- 9973647 TI - Pure red cell aplasia responsive to interferon-alpha in a patient with hepatitis C virus infection. AB - A 51-year-old man presented with severe anemia, mild splenomegaly and elevated serum aspartate aminotransferase and serum alanine aminotransferase levels. The bone marrow findings were consistent with pure red cell aplasia (PRCA) with a 'maturation arrest' at the level of pronormoblast. The patient has been transfusion-dependent for 8 months. Following diagnosis of chronic active hepatitis due to hepatitis C virus (HCV), therapy with interferon-alpha was initiated. Two weeks later, the hemoglobin level stabilized, and he has not required any transfusion ever since. In spite of ongoing HCV viremia, cessation of interferon therapy, and deterioration of the liver function tests, the patient, followed for 2 years, maintains a high-normal hemoglobin level. To the best of our knowledge, this is the first report of prolonged PRCA corrected by interferon-alpha therapy, with or without an ongoing HCV infection. We speculate that the 'maturation arrest' of the erythroid lineage seen in the bone marrow was the result of an immune mechanism, possibly induced by the HCV, and that the elimination of this mechanism, rather than the elimination of the HCV, provided the opportunity for regeneration of erythropoiesis. PMID- 9973648 TI - Immunocytochemical staining of normal and leukemic myeloid cells with the antibody EBM11 (CD68). PMID- 9973649 TI - Impact of carotid endarterectomy upon cognitive functioning. A systematic review of the literature. AB - BACKGROUND AND PURPOSE: The extent to which carotid endarterectomy (CEA) influences cognitive functioning has been the subject of a number of studies often with conflicting conclusions. This paper systematically reviews the literature in an attempt to clarify this issue. RESULTS: Although the majority of studies (16/28) reported an improvement in cognition after surgery, a substantial minority (12/28) found no change. Studies before 1984 tended to report an improvement, while later studies tended to report no change in cognition. Cognitive improvement was also more likely the longer the time interval between CEA and assessment. The studies were found to differ on many methodological factors, e.g. sample size, type of patient and control group, severity and side of carotid stenosis, the range of cognitive tests and timing of postoperative assessment. CONCLUSION: Given the conflicting findings, and the methodological issues, it is not possible to draw a clear conclusion regarding the impact of carotid endarterectomy upon cognition. Future research which pays attention to these methodological factors is needed in order to adequately resolve the current debate. PMID- 9973650 TI - Small centrum ovale infarcts--a pathological study. AB - There are limited data, mainly clinical and radiological, on small centrum ovale infarcts (SCOIs). From a consecutive series of 159 autopsy brains we identified 12 cases which on gross pathological examination harboured a total of 21 SCOIs. In the majority of lesions histology revealed a significant component of incompletely infarcted brain. Clinicopathological data suggested that the underlying mechanism was likely to have been cardioembolic in 3 cases, and possibly embolic from heart or aortic arch in a further 5. Two cases were due to ipsilateral carotid artery atheroma (i.e. 10 of 12 cases had possible embolic sources). The majority of lesions appeared to lie in arterial borderzones. The combined data suggest that SCOIs are pathologically and pathogenetically heterogeneous, and therefore that the term 'lacune' is inappropriate because this implies intrinsic small vessel disease as the underlying cause. Clinically, potentially treatable cardiac and large vessel pathology should be excluded. PMID- 9973651 TI - Neuropsychological features of dementia due to dural arteriovenous malformation. AB - We report two patients aged 65 and 61 years, who presented a subacute dementia with normal CT scan without contrast injection. Angiography showed a dural arteriovenous malformation. The patients improved dramatically with treatment of the malformation. Dementia was characterised by frontal dysfunction, emotional disorders, amnesic and praxic impairment. This neuropsychological pattern suggests a profile of global dementia in the field of vascular dementia. PMID- 9973652 TI - Age-related transcranial Doppler findings in the evaluation of cerebral circulation during postprandial and postural tests. AB - We used transcranial Doppler (TCD) to investigate whether there are cerebral circulation differences between young and elderly subjects in response to postprandial postural changes. Preprandial and postprandial systolic and diastolic blood pressure, heart rate, mean middle cerebral artery (MCA) velocity (Vmean MCA), systolic/diastolic MCA velocity ratio (Vs/Vd MCA) and pulsatility index (PI) were determined in 15 healthy elderly subjects (mean age 74.3 +/- 6.5 years) and in 10 younger subjects (mean age 31.6 +/- 7. 2 years) in the supine position and after a postural change. As compared with young subjects, elderly ones showed a greater postprandial systolic pressure decline (p < 0.05) associated with a significant decrease of Vmean MCA (p < 0.05), and a greater increase of Vs/Vd and PI (p < 0.05 both). We conclude that, as compared with young subjects, elderly ones have reduced cerebrovascular adaptive response to pressure modifications induced by postprandial postural changes. PMID- 9973653 TI - Recurrence of bleeding in patients with hypertensive intracerebral hemorrhage. AB - To characterize the recurrence of bleeding in patients who had hypertensive intracerebral hemorrhage (HICH), the authors reviewed 989 patients who underwent treatment for HICH between 1989 and 1995. Fifty-three patients (5.4%) had two episodes of HICH within a median interval of 22.9 +/- 16.3 months (range 1.5-72 months), and of these 3 (5.7%) had three episodes of HICH. The recurrence of bleeding most commonly occurred within 2 years of the first hemorrhage: in 66% of the 53 patients the second hemorrhage occurred soon after the first (within 1 year in 34%, within 1-2 years in 32.1%). The site of the second hemorrhage was different from the initial site in all patients. Only 1 patient had a third hemorrhage in the same site as the second hemorrhage. The common patterns of recurrence were 'ganglionic (putamen/caudate nucleus)-thalamic' in 26.8% and 'ganglionic-ganglionic' in 21.4%. The 'lobar-lobar' pattern was noted in only 2 patients. The volume of the hematoma was increased at the second hemorrhage. The overall mortality was 28.3%. The risk of recurrent hemorrhage significantly increased in the patients who had antihypertensive therapy of less than 3 months after the initial attack compared to those with further long-term therapy (p < 0.005). Long-term regular control for hypertension is needed to prevent recurrent hemorrhage. PMID- 9973654 TI - Percutaneous endoscopic gastrostomy after acute stroke: complications and outcome. AB - OBJECTIVE: To review the complications and outcome of percutaneous endoscopic gastrostomy placement (PEG) in 74 patients with acute stroke. PATIENTS AND METHODS: Medical record review and follow-up of patients with acute stroke admitted to a referral center. RESULTS: There were no immediate procedure-related complications. Late complications included aspiration pneumonia (11%), PEG occlusion and replacement (6%), accidental PEG removal (6%), wound infection (3%) and fatal gastrointestinal bleeding in 1 patient. In 18 patients (28%), PEG could be subsequently removed due to improvement in swallowing. CONCLUSION: PEG provides an effective alternative method of enteral feeding, but its impact on outcome remains uncertain. Late complications occurred in one third of the patients, but were seldom life threatening. Removal of the gastrostomy tube and resumption of oral feeding was possible in more than a quarter of the patients. All our patients who received PEG placement after acute stroke remained severely disabled; one third of the patients died from systemic complications of their stroke. PMID- 9973655 TI - Ebselen in acute middle cerebral artery occlusion: a placebo-controlled, double blind clinical trial. AB - A randomized, double-blind, placebo-controlled trial of ebselen was conducted in patients with complete occlusion of the middle cerebral artery. Ebselen or placebo granules suspended in water (150 mg b.i.d. ) were orally administered within 12 h of onset and continued for 2 weeks. The major end points were the maximum volume of cerebral infarct measured on follow-up computed tomography and the Glasgow Outcome Scale score at 1 month. One hundred and five patients were enrolled in this trial. Although the intent-to-treat analysis of 99 patients (43 given ebselen and 56 given placebo) did not reach statistical significance in reduction of the infarct volume (p = 0. 099), the protocol-compatible analysis of 83 patients with complete occlusion of the middle cerebral artery (34 given ebselen and 49 given placebo) determined a significant reduction using ebselen treatment (p = 0.034). A good outcome was seen in approximately 15% more patients from the ebselen group, but the difference between the 2 groups was not significant (p = 0.129). There was a corresponding significant reduction in the volume of cerebral infarct and an improvement in the outcome of patients who started treatment within 6 h of onset. These findings may suggest that ebselen protected the brain from ischemic damage in the acute stage. PMID- 9973656 TI - Knowledge of stroke in Hong Kong Chinese. AB - A random telephone survey on knowledge of stroke was conducted in 1, 238 Hong Kong Chinese. Most respondents realized that effective treatment was available, that stroke was preventable and that it could be fatal or disabling. Sudden unilateral limb weakness, sudden speech and language disturbances, and sudden vertigo and clumsiness were better recognized than other warning symptoms of stroke. A slightly better recognition of symptoms of stroke was seen in those with a belief of knowing about stroke, providing a correct description of stroke, those with a positive household history of stroke and those with a better knowledge of potential risk factors. Most respondents would choose desirable actions if stroke was suspected in their family members or themselves. Friends and relatives, newspapers and magazines, and mass media provided the major sources of their knowledge. PMID- 9973657 TI - Transient muteness followed by dysarthria in patients with pontomesencephalic stroke. Report of two cases. AB - Dysarthria is the principal motor abnormality following vascular damage to pontine paramedian structures, owing to the involvement of corticobulbar fibres. Here we describe 2 cases of adults affected by dysarthria following transient muteness as the result of a stroke in pontomesencephalic structures. Their clinical outcome was very similar to that of young patients who have undergone surgery of the 4th ventricle. Recently the importance of pons involvement has also been underlined in these cases. This case report suggests the existence of a functional network for speech, in which the pontomesencephalon is an important station for the triggering and the efficacy of verbal production. PMID- 9973658 TI - Protein S deficiency, activated protein C resistance and sticky platelet syndrome in a young woman with bilateral strokes. AB - BACKGROUND: Coagulation disorders are common in young adults (age less than 55 years) with ischemic stroke. OBJECTIVES: To describe a young woman with bilateral strokes of undetermined etiology who had three significant hemostatic disturbances. These were protein S deficiency, Factor V Leiden heterozygosity, and sticky platelet syndrome. The Factor V Leiden mutation was also present in one of her children. CONCLUSIONS: Young patients with cryptogenic stroke warrant a thorough evaluation for hypercoagulable states. More than one coagulation disorder can coexist in the same patient and the spectrum of hemostatic abnormalities may influence the patient's treatment and may have implications for screening of other family members. PMID- 9973659 TI - ber die laquo;Omnipotenz>> der Chelattherapie. AB - About the 'Omnipotence' of the Chelation Therapy In the eighties the 'method of treatment proven in many thousands of cases over 20 years' was transferred from the USA to Germany (enjoys a priori considerable faith) using very dubious promises. It was Clarke et al. who introduced this 'therapy' in 1955. The dubious promise was to maintain that the chelation therapy eliminates or alleviates symptoms in the case of the following illnesses: Alzheimer's disease, senility, schizophrenia, rheumatoid arthritis, osteoarthritis, gout, renal calculus, apoplectic coma, gallstones, multiple sclerosis, osteoporosis, chronic fatigue syndrome, varicose veins, hypertension, failure of memory, scleroderma, Raynaud's disease, digitalis intoxication, intermittent claudication, diabetic ulcer, disturbance of the blood supply, ulcer on the legs, snake poison, impotence, emotional difficulties, defective hearing, vision disorder. There is not the slightest proof of effectiveness for any of the listed indications. The burden of proof lies with the supplier. Even in the case of the relatively often examined peripheral atherosclerotic changes (claudicatio intermittens) there is no proof that EDTA has a greater effect than placebo. For coronary heart disease too there is no evidence for any usefulness of the chelation therapy beyond that of a placebo effect. Only controlled studies can help to improve the therapy in the sense of 'Evidence-based medicine'. Retrospective investigations on thousands of patients cannot 'prove' anything, although this is maintained again andagain. PMID- 9973660 TI - Mastodynon(R) bei weiblicher Sterilitat. AB - Mastodynon(R) for Female Infertility. Randomized, Placebo-Controlled, Clinical Double-Blind Study OBJECTIVE AND DESIGN: The effects of Mastodynon(R), an Agnus castus-containing preparation, were investigated in 96 women with fertility disorders in a prospective, randomized, placebo-controlled, double-blind study. PATIENTS AND METHODS: 38 women with secondary amenorrhoea, 31 women with luteal insuffciency and 27 women with idiopathic infertility received 30 drops of Mastodynon or placebo twice a day over a period of 3 months. OUTCOME MEASURE AND RESULTS: The outcome measure, which was pregnancy or spontaneous menstruation in women with amenorrhoea and pregnancy or improved concentrations of luteal hormones in both other groups, was achieved in 31 out of 66 women who were suitable for evaluation. It was achieved more often in the Mastodynon group compared to the placebo group (57.6% versus 36.0%, p = 0.069). 15 women conceived during the observation period (n = 7 with amenorrhoea, n = 4 with idiopathic infertility, n = 4 with luteal insufficiency). In women with amenorrhoea or luteal insufficiency, pregnancy occurred in the Mastodynon group more than twice as often as in the placebo group. Under therapy no hormonal changes were found at a 5% significance level. Only very few undesirable drug effects were observed. CONCLUSION: In women with sterility due to secondary amenorrhoea and luteal insufficiency, a treatment with Mastodynon can be recommended over a period of 3 to 6 months. PMID- 9973661 TI - Reliabilitat der energetischen Meridianmessung mit Prognos A(R). AB - Reliability of Energetic Meridian Measurement with Prognos A(R) OBJECTIVE: Is energetic measurement of the Traditional Chinese medicine (TCM) meridians with Prognos A a reliable method? PATIENTS: 30 healthy volunteers from the staff of the Stauferklinik, Schwa bisch Gmu nd, Germany. DESIGN: Measuremeuts are taken 4 times from each person at all terminal locations of the meridians (24 points) on fingers and toes with Prognos A. Breaks between each measurement run lastet 2-5 min. The values of skin resistance are compared. RESULTS: Reliabilities of the single meridian measurements range between 0.44 and 0.82 with an overall reliability of 0.72. Lowest reliability is seen in yang -hollow organs, probably a due to their intense lability. Mediating of 4 single runs shows a reliability of 0.9. CONCLUSIONS: Our measurement of reliability confirms Prognos A as a reliable device of determinating skin resistance, especially with repeated measurements. Variations of the readings are probably due to the special quality of the meridian system; increased variations of special meridians seem to be explainable by their characteristic features defined in TCM. PMID- 9973662 TI - Moderierende Variablen der Placebowirkung. AB - Modifying Variables of the Placebo Effect This essay discusses the question which psychological variables modify the placebo effect. Experimental as well as clinical studies were considered. The placebo model referred to in this article is the model of expectancy induction and expectancy effect. Besides the strength of expectancy several other variables foster the placebo effect. These are for example (a) the attitude and expectation of the doctor or placebo prescriber, (b) the motivation to give rise to a change as well as the importance of a change for the individual and (c) the extent of freedom of choice with regard to the acceptance of the treatment. On the other hand, high levels of self-awareness and experience with the method tend to inhibit the placebo effect. The placebo effect does not seem to be modified by traditional personality traits like generalized anxiety and hypnotic susceptibility. PMID- 9973663 TI - Familial language impairment: more English evidence. AB - Subjects between the ages of 9 and 22 with a history of familial language impairment were tested on a wide range of linguistic tasks. The data show that they are not different from the non-impaired members of their family or from external controls in their ability to hear and understand the morphological marker for plural or to understand a narrative, but they are significantly different in recognizing or correcting grammatical errors, in producing tense or number marking, and in understanding sentences with non-canonical word order. This pattern of deficits is similar to that which occurs cross-linguistically and in on-line processing tasks. These data support the hypothesis that these subjects do not build normal representations in their grammar nor construct productive grammatical rules. However, they are able to use other means such as memory and explicit rules to simulate grammar. PMID- 9973664 TI - Morphological representation in specific language impairment: evidence from Greek word formation. AB - Specific language impairment (SLI) is characterized by difficulties in inflectional morphology. Here we investigate SLI morphological competence to build and represent complex word structure. We examine the findings of two tasks where SLI subjects' performance is compared to that of controls: (a) plural formation and (b) compound formation. Subjects were presented with real and novel singular nouns in Greek and required to form plurals and compounds in each respective task. Both plural formation and compound formation are productive processes readily observed in non-impaired youngsters, with typical non-impaired errors being mostly constrained over-generalizations. The SLI children whose performance we consider here are below par in their morphological competence and the findings suggest that they do not build lexical representations that represent sublexical features or complex word-internal structure. PMID- 9973665 TI - The operation of rendaku in the Japanese specifically language- impaired: A preliminary investigation. AB - Rendaku is a well-documented phenomenon in Japanese phonology in which a word initial voiceless obstruent becomes voiced when it is the second member of a compound (e.g., ori + kami --> origami 'paper folding'). It was hypothesized that Japanese specifically language-impaired (SLI) children who appear to rely on explicit declarative memory as opposed to implicit procedural memory to learn language would have difficulty forming such compounds: word-initial voiceless obstruents would remain unvoiced in the second members of non-frequent and novel compounds. Six Japanese SLI children, ranging in age from 8;9 to 12;1, 6 age matched non-SLI children and 4 younger non-SLI children were given a word formation task involving three different categories of compounds. A significant difference in performance between the groups was found. The data indicate that the SLI children did not in fact voice most of the initial obstruents of the second member in non-frequent and novel compounds, whereas the age-matched non SLI children did voice the appropriate obstruents of all the compounds and the younger non-SLI children voiced some initial obstruents of all the compounds. Qualitative differences in the responses provide evidence that the SLI children did not have or were unable to construct a productive procedural rule of voicing. PMID- 9973666 TI - Prosodic features of familial language impairment: constraints on stress assignment. AB - This paper is part of a study of prosodic features of familial language impairment (FLI) in English. It reports the results of a set of experiments designed to investigate the factors that play a role in the assignment of stress to words which are longer than two syllables. It appears that stress assignment in FLI is constrained by a restriction limiting the maximal size of the stress domain to a bisyllabic unit, formally defined as the minimal prosodic word. We hypothesize that this restriction is responsible for variable patterns of word truncation, stress levelling and compounding that characterize the production of polysyllabic words. PMID- 9973667 TI - Uninflected structure in familial language impairment: evidence from French. AB - We present the results of 20 French subjects with familial language impairment (FLI) on a linguistic battery task, with an emphasis on verb production. The results show strong qualitative differences between the verb production of FLI subjects and that of controls. Language-specific factors do not seem to determine the production of verbs in French FLI individuals. Rather, verb frequency and the inflectional status (uninflected vs. inflected) of the form seem to be determining factors in correct/incorrect production of a verb in a sentence context. The phonetic structure of French inflection provides additional arguments against the hypothesis of a processing deficit in FLI subjects. French tense morphemes are stressed and salient, and should therefore be produced without problems, according to the processing hypothesis. We found evidence contrary to this postulate. We therefore submit that the morphological deficit hypothesis is supported by the French data. PMID- 9973668 TI - Serum leptin levels in young females with insulin-dependent diabetes and the relationship to hyperandrogenicity and microalbuminuria. AB - To investigate the relationship between leptin levels and IDDM with and without microalbuminuria, fasting serum levels of leptin, insulin, insulin-like growth factor-1 (IGF-1), sex hormone-binding globulin (SHBG), testosterone (SHBG) ratio, blood pressure and body mass index (BMI) were measured in 18 normo- and 11 microalbuminuric females with >5 years of IDDM, and 24 healthy controls in late puberty. Leptin levels were higher in micro- than normoalbuminuric IDDM patients, and lower in healthy controls than in both IDDM groups (p < 0.05, respectively). In multiple regression analysis, presence of IDDM and BMI independently contributed to increased leptin values (R2 = 0.34, p < 0.001). Including IDDM females only, solely low IGF-1 and high testosterone/SHBG were associated with leptin (R2 = 0.39, p = 0.009). Albumin excretion rate (AER) was correlated to leptin (r = 0.48, p = 0.01). With AER as the dependent variable only serum leptin and diastolic blood pressure added to the regression (R2 = 0.59, p < 0.001). In conclusion, serum leptin, independently of BMI, is: (1) increased in IDDM females of late puberty; (2) associated with low IGF-1 and hyperandrogenemia, and (3) related to increased albumin excretion rate in IDDM females. PMID- 9973669 TI - Longitudinal evaluation of salivary cortisol levels in full-term and preterm neonates. AB - The aim of the present study was to test the practicability of sequential cortisol determinations in saliva of low birth weight neonates and to evaluate the impact of systemic and inhaled glucocorticoid therapy on saliva concentrations of cortisol in preterm neonates with bronchopulmonary dysplasia (BPD). Salivary cortisol levels were measured by RIA in saliva samples from 10 full-term and 10 preterm healthy neonates and from 20 preterm neonates with BPD during systemic [dexamethasone (DEX); n = 10] or topical steroid therapy [budesonide (BUD); n = 10]. Saliva samples of each individual were collected on 3 consecutive days at 06.00, 12. 00, 18.00 and 24.00 h. Cortisol levels in saliva ranged from 0.8 to 60.6 nmol/l (median 6.5 nmol/l) in full-term neonates, from 0.6 to 52.1 nmol/l (median 5.5 nmol/l) in preterm neonates, from 0.4 to 14. 0 nmol/l (median 1.0 nmol/l) in preterm neonates treated with DEX and from 0.4 to 15.2 nmol/l (median 2.5 nmol/l) in preterm neonates treated with BUD. Autocorrelation analysis revealed a distinct endogenous cortisol rhythm in 2 of the 10 healthy full-term neonates and in 3 of the 10 healthy preterm neonates with a wavelength of 12-30 h. Salivary cortisol levels in preterm neonates treated with DEX or BUD were significantly lower than those measured in healthy preterm neonates. These results demonstrate that the measurement of salivary cortisol levels is a reliable and practicable way of assessing adrenal function in full-term and preterm neonates. This study also shows for the first time that some neonates display an endogenous cortisol rhythm which is not coupled to the exogenous day/night cycle. Furthermore, systemic and nebulized glucocorticoids suppress adrenal function in low-birth-weight neonates. After treatment these children should be closely monitored for potential adrenal insufficiency. PMID- 9973670 TI - Altered bone mineral density in patients with complete androgen insensitivity syndrome. AB - Androgens have major influences on the regulation of bone mineralization. Because of their unique peripheral metabolism androgens may act on bone via activation of the androgen and/or estrogen receptor. Patients with complete androgen insensitivity syndrome (cAIS) are natural models to assess androgen actions on bone. We studied bone mineral density (BMD) in 10 patients with cAIS (mean age 13.70, range 4.7-19.8 years); 3 patients were studied before gonadectomy; the others were castrated and 6 were on hormonal replacement therapy. The BMD area (aBMD) was measured by dual energy X-ray; lumbar 'apparent' volumetric density (vBMD) was calculated using the formula vBMD = aBMD x [4/(pi x width)]. In the patients, aBMD (0.72 +/- 0.16 g/cm2) and vBMD (0.23 +/- 0.04 g/cm3) were significantly (p < 0.001) reduced in comparison with those of a control group (n = 15, age 5.0-20.5 years: aBMD 1.028 +/- 0.20 g/cm2; vBMD 0.35 +/- 0.04 g/cm3). Both aBMD and vBMD were also reduced in comparison with normal values for males (aBMD -2.66 +/- 0. 99 SDS, p < 0.001; vBMD -3.08 +/- 1.53 SDS, p < 0.0005) and females (aBMD -2.88 +/- 1.05 SDS, p < 0.001; vBMD -2.84 +/- 1.18 SDS, p < 0. 0007). Real lumbar bone density, assessed by computed tomography in 1 patient, was also reduced (-6.2 SDS and -3.5 SDS for male and female normal values, respectively). Biochemical markers of bone metabolism were normal and not significantly different in patients and controls. Girls with cAIS did not have more fractures than controls. In conclusion, both aBMD and vBMD are reduced in cAIS patients, while bone turnover and the fracture risk seem not to be increased. Our data indicate that both androgens and estrogens may be required for acquisition of bone density during childhood. PMID- 9973671 TI - Does vitamin D receptor polymorphism influence the response of bone to brisk walking in postmenopausal women? AB - Vitamin D receptor (VDR) polymorphism may be a genetic factor affecting bone mineral density (BMD). This study examined the interaction of VDR genotype with the effect of an exercise intervention on bone measurements in UK postmenopausal women. 33 walkers, who completed 20.4 +/- 3.9 (mean +/- SD) min day-1 of brisk walking over 1 year, and 36 controls agreed to give DNA samples. BMD was measured at the lumbar spine, femoral neck and calcaneus by dual energy X-ray absorptiometry and broadband ultrasonic attenuation (BUA) was measured at the calcaneus. VDR genotype was determined by BsmI restriction fragment length polymorphisms and the presence, or absence, of the restriction site was signified by 'b' or 'B', respectively. At baseline there was no significant difference in BMD between VDR genotypes, but BUA was significantly higher in the BB genotype than in the Bb or bb genotype. Although there was no significant difference in 1 year change (%) in BMD and BUA between the three genotypes, the 1-year changes in spinal BMD and BUA in the bb walkers (0.75 and 2.35%, respectively) were significantly different from those in the bb controls (-1.25 and -6.10%, respectively). These results suggest that in the bb genotype of VDR, bone may be more responsive to exercise than in other VDR genotypes in British postmenopausal women. PMID- 9973672 TI - Diagnosis and treatment of growth hormone deficiency in children and adolescents: towards a consensus. Ten years after the Availability of Recombinant Human Growth Hormone Workshop held in Pisa, Italy, 27-28 March 1998. AB - This article summarizes the content of an international workshop on the diagnosis and treatment of growth hormone deficiency (GHD) in children and adolescents that was held in Pisa, Italy, in March 1998. The issues discussed are divided into those addressing the definition and diagnosis, and the treatment of GHD in children and adolescents, and those concerning the transition of patients with GHD from adolescence to adulthood. Recommendations are presented for improving the diagnosis and management of children and adolescents with GHD and issues are highlighted that require further studies to be undertaken before recommendations can be made. PMID- 9973673 TI - The embryogenesis of congenital vertebral dislocation: early embryonic buckling? AB - Congenital vertebral dislocation (CVD) is a rare congenital spinal malformation characterized by a translatory or rotatory vertebral displacement, or both, at a single level, that results in an abrupt angulation of the neural canal. The more caudal vertebra is dysplastic and appears at first glance to be posteriorly dislocated into the vertebral canal as a posterior hemivertebra, but is actually well aligned with the more caudal vertebral column. Unfortunately, the present classification of complex congenital vertebral anomalies is confusing, and CVD has been grouped together with other congenital vertebral malformations under the terms 'segmental spinal dysgenesis', 'medial spinal aplasia', and others. Moreover, a putative embryonic mechanism has never been proposed for CVD. Based upon our experience with 6 children and a critical review of the literature, we identify CVD as a distinct entity having characteristic anatomical features. We propose a novel putative embryonic mechanism - early embryonic 'buckling' - which likely occurs by the 6th embryonic week, prior to the period of axonal outgrowth and the beginning of vertebral chondrification. PMID- 9973674 TI - Hypothalamic hamartoma associated with multiple congenital abnormalities. Two patients and a review of reported cases. AB - We report 2 patients with hypothalamic hamartoma associated with multiple congenital abnormalities and analyze 42 (including our own) reported cases, including our 2 cases, of hypothalamic hamartoma or hypothalamic hamartoblastoma with multiple congenital abnormalities, to understand the timing of their occurrence and clarify the prognosis. To this end, we classified them into lethal and nonlethal cases. We found poly- and syndactyly, cleft or high-arched palate and nose abnormalities to be important manifestations of this syndrome. Major organ abnormalities and CNS and endocrine abnormalities occurred frequently among the lethal cases, very likely indicative of a disturbance of embryogenesis between gestational days 34-37 and thus implicated in a negative prognosis. PMID- 9973675 TI - Pediatric intracranial epidural abscess secondary to an infected scalp vein catheter. AB - The authors present a case of a 5-week-old infant developing a retrotorcular epidural abscess as a result of an infected scalp vein catheter. The abscess developed in the absence of sinusitis, otitis, trauma, or prior surgery. The diagnosis of epidural abscess was made on the basis of magnetic resonance imaging and ultrasound-guided aspiration of the fluid collection. An identified strain of Staphylococcus epidermidis was cultured from both the intravenous catheter and the abscess. The patient underwent a suboccipital craniectomy with drainage of the abscess and a 6-week total course of intravenous antibiotics. Magnetic resonance imaging 4 months after the procedure and 2.5-year pediatric clinic follow-up have demonstrated no evidence of neurologic deficit or recurrence. When present, a scalp vein catheter must be considered as an etiologic agent for an intracranial epidural abscess in this age-group. PMID- 9973676 TI - Diffuse cerebral vasospasm with ischemia after resection of a cerebellopontine angle primitive neuroectodermal tumor in a child. AB - This case report describes a 15-month-old female who developed diffuse cerebral vasospasm after resection of a cerebellopontine angle primitive neuroectodermal tumor. The patient developed an acute dense left hemiparesis 16 days postoperatively with partial right ptosis. Initial magnetic resonance imaging and diffusion study were unremarkable, though a magnetic resonance angiography 1 day later demonstrated severe intracranial vasospasm of both carotid and vertebral arteries. The vasospasm was confirmed with cerebral angiography. The patient progressed to bihemispheric infarcts with laminar necrosis despite combination therapy with anticoagulation, pharmacological hypertension, hypervolemia, and nimodipine. The clinical course, radiographic, and pathological findings are presented. PMID- 9973677 TI - Fusiform dilatations of the internal carotid artery following surgery for pediatric suprasellar tumors. AB - Fusiform dilatations of the internal carotid artery (FDCA) represent a vascular complication following surgery for suprasellar tumors in children. In a long-term follow-up of 62 children we identified 7 children (11.3%) with a FDCA. In all children the FDCA was present within 15 months following surgery. It was not related to radiotherapy or a distinct histology. In 3 children the FDCA remained unchanged during the follow-up, in 3 children there was a progression and 1 child revealed a regression within 6 months. Clinically the FDCA was inapparent in all cases and not treated. In a follow-up study of an adult population who underwent surgery for suprasellar tumors no case of FDCA was encountered. Potential pathomechanisms and indications for treatment are discussed. PMID- 9973678 TI - Treatment of posthemorrhagic hydrocephalus in the preterm infant with a ventricular access device. AB - Intraventricular hemorrhage (IVH) and subsequent posthemorrhagic hydrocephalus (PHH) commonly complicate the course of extremely preterm infants. Many methods for treating the hydrocephalus have been used, none of which are ideal. We present the largest series of infants with PHH treated with one modality, the ventricular access device (VAD). One hundred and forty-nine preterm infants with PHH were treated by placement of a VAD and serial taps to control intracranial pressure and ventricular size. Variables recorded include gender, race, gestational age, weight at birth, IVH grade, incidence of VAD infection, malfunction or local wound problems and indwelling time to either shunt placement or VAD removal. Of the 149 preterm infants, 91 were males and 58 females. The average birth weight was 994 g and the average gestational age at birth was 26.3 weeks. Three infants were IVH grade 1, 8 were grade 2, 62 were grade 3 and 76 were grade 4. VAD occlusion occurred in 15 infants (10%). Nine infants required contralateral VAD placement for a trapped ventricle. VAD infection occurred in 12 infants (8%), 5 of whom were treated successfully with a combination of systemic and intra-VAD antibiotics without removal of the VAD. The total rate of revision was thus 20% (15 for occlusion, 9 for trapped ventricle, 7 for infection). Wound problems were minimal and consisted of 4 cerebrospinal fluid leaks and 14 subgaleal fluid collections. For the 133 survivors, the rate of shunt placement was 88%. The VAD, while not ideal, is an excellent treatment at this time for PHH. It can be utilized for several months with acceptable rates of infection, blockage and wound complications. The VAD tap is simple to perform, not disruptive to minimal stimulation protocols, and can be done by physician extenders. In addition, medications can be administered via the access device, thus allowing treatment of some infections without VAD removal as well as instillation of thrombolytic agents such as urokinase. PMID- 9973679 TI - Avoiding complicated shunt systems by open fenestration of symptomatic fourth ventricular cysts associated with hydrocephalus. AB - Optimal treatment of the hydrocephalic patient with symptomatic Dandy-Walker malformation or trapped fourth ventricle remains controversial. We describe 6 patients with symptomatic Dandy-Walker malformation or trapped fourth ventricle and hydrocephalus that were treated with an aggressive cyst fenestration. Four of the 6 patients had previously undergone five or more failed shunt procedures. There were no complications associated with surgery, and 5 of the 6 patients (83%) have remained asymptomatic with respect to their posterior fossa cysts. One patient has required subsequent fourth ventricular shunt placement. Median follow up was 26 months (range 12-66 months). We suggest that suboccipital craniectomy and open fenestration is a valid treatment option in hydrocephalic patients with symptomatic Dandy-Walker malformation or trapped fourth ventricle. Although the associated lateral ventriculomegaly will probably still require a ventriculoperitoneal shunt, the absence of a cystoperitoneal shunt system seems to minimize the incidence of complications and reoperation. PMID- 9973680 TI - Visually evoked potentials in 52 children requiring operative repair of craniosynostosis. AB - We evaluated the prevalence of pathological visually evoked potentials (VEP) before the appearance of papilledema or other signs of elevated intracranial pressure in children suffering from craniosynostosis. In 52 children (19 girls, 33 boys, median age 7.6 months, mean age 7.6 months, range from 3 to 34 months) preoperative VEP were analyzed. In 13 patients, pathological VEP were observed. In all children, both eyes were involved. Only 1 child suffered from papillar anomalies. Latency was pathological in 12 children, whereas the amplitude was suppressed in only 2 children. In all children with preoperative pathological VEP, postoperative controls (n = 4) were improved or normal. Thus, VEP may be the first test for neuronal damage in craniosynostosis. PMID- 9973681 TI - A method of cranioplasty using coralline hydroxyapatite. AB - INTRODUCTION: Current cranioplasty materials include autologous or homologous bone grafts, wire mesh and methyl methacrylate, either alone or in combination. However, each material has its own unique disadvantages. Although hydroxyapatite has been used extensively in other specialties as a bone substitute, the coralline form has rarely been used to repair cranial bone defects. Coralline hydroxyapatite, similar to that found in bone, provides a matrix on which living tissue can form and grow. Because it is an ideal bioimplant, a method of cranioplasty using coralline hydroxyapatite was employed. METHODS: The hydroxyapatite granules are mixed with Avitene and autologous blood to form a paste which can be contoured as needed. RESULTS: Over the past few years, we have used hydroxyapatite either alone or in combination with tantalum mesh in 19 pediatric patients for a variety of conditions. The cosmetic results were good to excellent. Furthermore, postoperative CT scans have documented bony substitution of the hydroxyapatite granules. Follow-up ranged from 1 to 43 months with a mean of 26 months. CONCLUSION: In neurosurgical procedures when a bone substitute is needed, hydroxyapatite is an effective alternative to other currently available materials. PMID- 9973682 TI - Chemical meningitis from bile reflux in a lumbar-gallbladder shunt. AB - OBJECTIVE AND IMPORTANCE: The gallbladder is used to divert cerebrospinal fluid (CSF) in patients with hydrocephalus when all other sites have been exhausted. This is seen in hydrocephalic patients who have reached teenage years but have undergone multiple shunt revisions, abdominal operations and repeated neck vein cannulations during childhood. One complication of the lumbar-gallbladder shunt is discussed as well as its pathophysiologic theory and management. CLINICAL PRESENTATION: A case of a patient with a lumbar-gallbladder shunt who developed chemical meningitis from reflux of bile into the CSF space is presented. The patient presented with generalized seizures. INTERVENTION: Included: ventilatory support, externalization of the shunt, correction of the metabolic abnormalities and administration of anticonvulsants and steroids. CONCLUSION: This case illustrates an unusual occurrence of reflux of bile into the CNS through a lumbar gallbladder shunt in a patient with long-term complex communicating hydrocephalus. It also demonstrates its mode of presentation and successful management. To our knowledge, this is the first case report of its kind. PMID- 9973683 TI - Pulmonary defence mechanisms. AB - Lung defence involves a wide array of mechanisms needed to remove inhaled particles and organisms. The various innate immune processes which take place either in the central or in the more distant airways are reviewed. The recruitment and the development of an adaptive immunity following the innate response are described. This entails the production of secretory immunoglobulins in the airways and either the influx of polymorphonuclear neutrophils in the alveoli to phagocytose more or less opsonized organisms or the activation of the T lymphocyte response to improve the removal of intracellular pathogens. PMID- 9973684 TI - The lung in diabetes mellitus. PMID- 9973685 TI - Diabetes mellitus induces a thickening of the pulmonary basal lamina. AB - Long-term diabetes mellitus (DM) is characterized by widespread alterations of basal lamina (BL). The purpose of the present work was to verify whether the lung is also a target organ damaged in DM. Electron microscopy was performed on lung and kidney samples (autopsic material) from 6 diabetics and 6 control subjects studying the thickening of BL of different structures (alveolar epithelial BL, endothelial capillary BL, both fused BL, BL of the glomerular capillary endothelium and BL of the renal tubules). The results were as follows: (1) alveolar epithelial BL (mean +/- SD) = 121 +/- 11 nm in controls and 176 +/- 27 nm in diabetics (p < 0.01), (2) endothelial capillary BL = 164 +/- 14 nm in controls and 223 +/- 27 nm in diabetics (p < 0.001), (3) both BL fused = 222 +/- 23 nm in controls and 316 +/- 62 nm in diabetics (p < 0.01), (4) BL of the glomerular capillary endothelium = 374 +/- 44 nm in controls and 626 +/- 249 in diabetics (p < 0.05) and (5) BL of the renal tubules = 602 +/- 94 nm in controls and 1,083 +/- 376 nm in diabetics (p < 0. 05). All parts of the lung are equally affected by DM. The thickening of BL is of the same magnitude in lung and kidney. There is no relationship between the thickening of the lung BL and the known duration and type of DM. PMID- 9973686 TI - Pulmonary gas exchange in life-long nonsmoking patients with diabetes mellitus. AB - In a companion paper, we have found that the alveolar epithelial basal lamina, endothelial basal lamina and both fused were significantly thicker in 6 autopsied diabetics than in 6 control subjects. The purpose of the present work was to assess whether these lesions have detrimental effects on gas exchange. We investigated 20 life-long nonsmoking subjects: 10 healthy subjects and 10 insulin dependent diabetics. All of them had one to four diabetic complications of the following organs: kidney, retina, nerves or arteries. Their pulmonary gas exchange and their transfer factor were measured at rest and during two levels of submaximal exercise. Spirometric data, specific airway conductance, transfer factor, transfer coefficient, oxygen consumption and arterial blood gases were normal and almost identical in both groups. In conclusion, the thickening of lung basal laminae has no detrimental effect on pulmonary gas exchange in insulin dependent diabetics with peripheral complications. PMID- 9973687 TI - Oxygen uptake and cardiac performance in obese and normal subjects during exercise. AB - Work capacity and cardiopulmonary performance were studied in a group of 11 young obese subjects (BMI 39.9 kg/m2) and a group of 10 young normal subjects (BMI 22 kg/m2). First of all they underwent an incremental cycle ergometer test up to exhaustion. Subsequently, every subject of the two groups performed a constant work rate test at different work loads to estimate cardiac output (Q) below anaerobic threshold (AT) by a 20-second CO2 rebreathing method. Obese subjects had a significantly lower AT (79 vs. 109 W). The ratio between oxygen uptake and heart rate (VO2/HR) (O2 pulse) was higher in the obese group; nevertheless, this variable became significantly lower if we took into consideration the ratio between O2 pulse and kilogram fat-free body mass or kilogram body weight. Both these observations suggest that their reduced work tolerance is linked with a reduced oxygen supply to the muscles in activity. Q increased in similar ways in obese and normal subjects at the preset work rates. The ratio Q/body surface (cardiac index; CI) that we considered in order to try to minimize the differences in body sizes between the two groups, increased less in response to increasing work rates in our obese subjects than in normal subjects. As a whole, these data appear to be in line with a relatively less efficient cardiac performance during progressive work rates in obese subjects. PMID- 9973688 TI - Selection of reproducible forced expirograms: percentage or fixed-volume criterion. AB - The aim of this study was to evaluate whether the intrasession reproducibility of forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1) depends on height and lung volume. FVC tracings of 740 subjects (350 males) from a general population sample living in North Italy were analyzed. Subjects filled out a standardized questionnaire and performed three acceptable FVC maneuvers following the American Thoracic Society recommendations. The differences between the largest and the second largest FVC and FEV1 were computed as absolute (DeltaFVC, DeltaFEV1) and as percentage values (DeltaFVC%, DeltaFEV1%). The higher the tertiles of the largest FVC and FEV1 were, the higher were DeltaFVC and DeltaFEV1. Regarding FVC, borderline differences in both sexes for DeltaFVC and in males significant differences for DeltaFVC% were found among the tertiles. Regarding FEV1, in both sexes DeltaFEV1 significantly differed among the tertiles. DeltaFVC and DeltaFEV1 correlated with height and lung volume in both sexes, except for DeltaFVC versus the largest FVC in females. When DeltaFVC and DeltaFEV1 were analyzed with respect to respiratory symptoms/diseases and smoking habit, no significant differences were observed in both sexes, except for DeltaFEV1 between ever- and never-smoking males. It may be concluded that the intrasession within-subject variability of FVC and FEV1 is proportional to lung volume and height, regardless of the sex, presence of symptoms and smoking habit. Thus, our results confirm the usefulness of a reproducibility criterion based on a percentage rather than on a fixed volume. PMID- 9973690 TI - Using 99mTc-DTPA radioaerosol inhalation lung scintigraphies to detect the lung injury induced by consuming Sauropus androgynus vegetable and comparison with conventional pulmonary function tests. AB - Consuming Sauropus androgynus, a Malaysian plant, to reduce body weight began to become fashionable in Taiwan in 1994. According to some reports, people consuming this vegetable developed lung injuries. From July to November 1995, there were 81 nonsmoking women admitted to our hospital. Thirty-six cases had respiratory symptoms/signs and the remaining 45 had no symptoms/signs. We investigated these patients with pulmonary function tests (PFT) and technetium-99m DTPA radioaerosol inhalation lung scintigraphies (DTPA lung scan), a test to evaluate the lung ventilation and alveolar epithelial permeability. Eighteen patients had abnormal results in PFT, including obstructive type (n = 17), restrictive type (n = 5), and both (n = 4). There were 33 patients with abnormalities in DTPA lung scans, including unhomogeneous deposition of DTPA radioaerosols (n = 19), faster clearance of radioaerosols from lung (n = 26), and both (n = 12). Analyzing the results, we found that the patients with respiratory symptoms had a higher incidence of abnormal results of PFT and DTPA lung scans than the patients without respiratory symptoms (p < 0.05). Besides, we found that the DTPA lung scan was more sensitive than chest x-ray and PFT in detecting the lung injuries related to the consumption of S. androgynus (p < 0.05). Consuming S. androgynus can result in symptomatic or asymptomatic lung injuries, manifested as obstructive or restrictive ventilatory impairment, unhomogeneous radioaerosol distribution, and increased alveolar epithelial permeability. In addition, measurement of the 99mTc-DTPA clearance is the most sensitive test to detect the lung injuries caused by consuming S. androgynus. PMID- 9973691 TI - Effects of air pollution and weather conditions on asthma exacerbation. AB - BACKGROUND: Meteorological conditions and a high concentration of air pollutants have been associated with increased respiratory morbidity. However, few studies have examined the association between asthma exacerbation and air pollution. OBJECTIVES: In the present study, the possible relationship of the concentration of black smoke and SO2 in the air, the local weather conditions and emergency room visits for asthma is investigated. METHODS: The weekly total of emergency room admissions for asthmatic adults during a 1-year period was recorded together with daily metereological conditions (average temperature, humidity, rainfall, wind speed and barometric pressure) and average weekly levels of daily pollutant concentrations (black smoke and SO2). The relationship was assessed by stepwise regression linear models and analysis of variance. The analysis took into account season and metereological variables. RESULTS: Both air pollutants correlated significantly with emergency room admissions for asthma (SO2 [r = 0. 32], black smoke [r = 0.35]); however, multiple regression analysis showed that black smoke was the only significant predictor of weekly visits. There were approximately 3.5 admissions a week per SD of change (34.6 microg.m-3). There were no significant correlations between weekly emergency room visits and the weather variables. Analysis of the data stratified by season and weather conditions demonstrated that the association of black smoke with asthma exacerbation was more pronounced in autumn (r = 0.67) or when temperatures were higher than average. CONCLUSION: In our city, a high concentration of certain air pollutants is indeed associated with an increase in the number of hospital emergency room admissions for asthma. PMID- 9973692 TI - Effect of endothelin-1 on the serotonin-induced contraction of smooth muscle in the guinea pig trachea. AB - BACKGROUND: Endothelin (ET), a potent constrictor of smooth muscle including that of the airways, may contribute to the development of airway hyperresponsiveness. OBJECTIVE: To investigate the role of ET-1 on the airway smooth muscle, we examined the effects of ET-1 on the serotonin-induced contraction of guinea pig tracheal smooth muscle. METHODS: The changes in isometric tension evoked by serotonin were measured before and after the application of a subthreshold dose (a dose which did not induce smooth muscle contraction by itself) of ET-1. RESULTS: Serotonin caused smooth muscle contraction in a dose-dependent manner. The subthreshold doses of ET-1 (1 pM) and sarafotoxin 6c (1 pM), a selective ETB receptor agonist, were found to potentiate significantly the contraction induced by serotonin. A potentiating effect of ET-1 was not altered by indomethacin or calphostin C, a protein kinase C inhibitor. CONCLUSION: These results suggest that a subthreshold concentration of ET-1 can potentiate serotonin-induced contraction of smooth muscle through the activation of ETB receptor, while in contrast cyclooxygenase and protein kinase C were found not to be involved in this mechanism. PMID- 9973693 TI - Severe toxic laryngo-tracheo-bronchitis in a drunken man. PMID- 9973694 TI - Casual recognition of an azygous continuation of the inferior vena cava in a patient with lung cancer. AB - Anomalous continuation of the inferior vena cava with an azygous vein is a rare vacular anomaly. The enlarged venous system may simulate adenopathies or mediastinal and retroperitoneal masses on the radiographs. We describe the case of a patient with lung cancer - a pathological condition which may cause adenopathies at these sites - and a dilated azygous-hemiazygous system resulting from failure of formation of the hepatic segment of the inferior vena cava. PMID- 9973695 TI - Mesalazine-induced eosinophilic pneumonia. AB - A 35-year-old woman with a 6-month history of ulcerative colitis and treatment with oral mesalazine (5-aminosalicylic acid) developed dry cough, low-grade fever and bilaterally wandering pulmonary infiltrates. Improvement in clinical symptoms and radiological abnormalities occurred spontaneously after discontinuation of mesalazine. The transbronchial lung biopsy demonstrated the organizing stage of eosinophilic pneumonia. Drug lymphocyte stimulation test was positive for mesalazine and negative for sulfasalazine and sulfapyridine. The present case indicates that although mesalazine-induced eosinophilic pneumonia is an extremely rare entity, its possibility should be fully considered in patients developing unexplained respiratory symptoms while on mesalazine therapy. PMID- 9973696 TI - Hemoglobin SC disease presenting as acute chest syndrome with ventilation perfusion mismatches. AB - Acute chest syndrome, characterized by fever, chest pain and pulmonary infiltrates, is a known complication of hemoglobin SC disease. A 41-year-old African male with previously unknown hemoglobinopathy developed an acute episode of fever, chest pain and dyspnea right after surgery for retinal detachment. The patient was suspected of having pulmonary thromboembolism. This was further suggested by a 'high probability' ventilation-perfusion scan. However, a pulmonary angiogram revealed no evidence of thromboembolism. Subsequently, the patient was recognized to have hemoglobin SC disease, with the acute chest syndrome. After appropriate treatment with antibiotics, hydration and exchange transfusion, the patient underwent another surgery without complications. PMID- 9973697 TI - Metastatic pulmonary epithelioid hemangioendothelioma with peculiar radiographic features. AB - We report a case of a pulmonary epithelioid hemangioendothelioma presenting as a solitary pulmonary nodule with subsequent systemic spread, including histologically documented gingival metastasis. Chest radiography and computed tomography at initial evaluation showed a solitary 2 cm pulmonary nodule, associated with pleural indentation and vascular convergence. The tumor later spread systemically, including multiple pulmonary nodules, bilateral pleural effusions, and gingival swelling and erosion. A biopsy of the gingival lesion showed histologic features identical to that of the lung biopsy. PMID- 9973698 TI - Severe barium sulfate aspirationinto the lung: clinical presentation, prognosis and therapy. AB - Aspiration of large amounts of barium sulfate is a rare incident during radiographic contrast procedures. Here we describe two patients, who developed acute dyspnea after aspiration of significant amounts of barium into the lung during an upper gastrointestinal radiographic contrast study. The regions of the lung involved depended on the position of the patients during and after aspiration. Arterial blood gas analysis revealed hypoxemia due to alveolar shunt with V/Q distribution disturbances. Bronchoscopy was performed to extract the contrast medium from the tracheobronchial tree. The patients could be discharged a few days later with normal lung function. Long-term prognosis is generally excellent due to the inert character of barium sulfate, even though impressive radiographic findings remain. PMID- 9973699 TI - Lung abscess caused by Paecilomyces lilacinus. AB - We report the case of a 57-year-old man who was referred to our department for further investigation of an abnormal chest shadow. Radiography on admission demonstrated a coin lesion in the right hilum. To make a final diagnosis, right middle lobectomy was performed and the mass was revealed to be a fungal abscess. Further examination confirmed that the fungus was Paecilomyces lilacinus. This is the first reported case of lung abscess caused by P. lilacinus in an otherwise healthy person. PMID- 9973700 TI - An unusual case of esophageal tuberculosis in an adult. AB - Tuberculous infection of the esophagus is a rare disease and usually occurs secondary to tuberculous mediastinal lymphadenopathy. We report a 74-year-old woman presenting with dysphagia and weight loss. The chest radiograph showed punctuated calcifications lining from the right hilar region to the paracardiac region. Upper gastrointestinal endoscopy revealed a 0.5 x 5 cm lesion localized in the 25th cm of the esophagus covered partly with normal mucosa, partly demonstrating ulcerous areas. Biopsy revealed granulomatous infiltrates being tuberculoid in type. Thorax CT showed a calcified lymph node at the right hilum. The patient did not give consent to therapy and died 1 month later. PMID- 9973701 TI - What is your diagnosis? Multiple unilateral nodular pulmonary lesions in a lung transplant recipient. Diagnosis: focal intrapulmonary hemorrhage following transbronchial lung biopsy. PMID- 9973702 TI - Computer generated mandibular model: surgical role. AB - A life-size nylon model of a traumatized mandible was produced from CT scan data by the process of laser sintering. The model was used for pre-operative planning and for production of surgical aids in order to facilitate the restoration of a large bony defect. Vascularized iliac crest bone was harvested, titanium implants placed and the bone then grafted to the mandible. PMID- 9973703 TI - Primary malignant melanoma of the oral cavity. Report of an unusual case. AB - Primary malignant melanoma is only rarely found in the oral cavity (estimated at between 0.2 and 8 per cent of all melanomas) and occurs approximately four times more frequently in the oral mucosa of the upper jaw, usually on the palate or alveolar gingivae. A case is reported of a malignant melanoma in the mouth of a 74 year old male, which was originally diagnosed as reactive denture hyperplasia caused by a ill-fitting upper denture. Correction of the denture fault failed to stop the growth of the mass, which was therefore removed surgically. Histological examination revealed a melanin-producing tumour. A partial maxillectomy was performed and there was no evidence of recurrence over a three year follow-up period. PMID- 9973704 TI - Postoperative bleeding with factor VII deficiency: case report. AB - Factor VII deficiency was diagnosed during haematological investigation of a patient with multiple occurrences of postoperative bleeding after surgical extraction of an impacted upper left canine. The bleeding was eventually stopped with local measures without resorting to blood product transfusion which may have been necessary if local measures had failed to control bleeding. Abnormalities were also found in subsequent blood profiles and coagulation tests in other members of the patient's family. PMID- 9973705 TI - Supernumerary tooth in the maxillary sinus: case report. AB - The ectopic development of teeth has been reported in many locations including the nasal cavity, maxillary sinus and the chin. Ectopic teeth may be permanent, deciduous or supernumerary. A case is presented in which a supernumerary tooth erupted into the maxillary sinus of an 11 year old boy. PMID- 9973706 TI - Tongue piercing: case report and review of current practice. AB - Although oral piercing has been an uncommon practice in the Western world, the insertion of metal objects into intra-oral and peri-oral pierced sites is growing in popularity. Tongue piercing is one such practice whereby a metal barbell is inserted into the tongue after piercing with a 14-16 gauge needle. Pain, swelling and infection are the most serious consequences associated with this procedure. Other adverse outcomes include mucosal or gingival trauma, chipped or fractured teeth, increased salivary flow, calculus build-up, and interference with speech, mastication and swallowing. This article presents a case report on tongue piercing and highlights the procedure involved. Special attention is given to complications and dental implications associated with such an unusual practice. PMID- 9973707 TI - Fibrous dysplasia of the jaw bone: a review of 15 new cases and two cases of recurrence in Jamaica together with a case report. AB - The authors reviewed 15 new cases of fibrous dysplasia of the jaw bone and two cases of recurrence seen in Jamaica between 1980 and 1995. Only cases which had a histological confirmation of fibrous dysplasia were included. The clinical behaviour and radiological findings of these cases were studied from the case files, either at the Cornwall Regional Hospital or the Kingston Public Hospital in Jamaica. PMID- 9973708 TI - Prevalence of dental anomalies in orthodontic patients. AB - The prevalence of dental anomalies including agenesis, crown shape, tooth position, root shape, and invagination were examined in 111 orthodontic patients; 74.77 per cent of the patients exhibited at least one dental anomaly. Invagination was found to be the most prevalent anomaly, whereas supernumerary teeth and root dilaceration were the least frequent anomalies. Dental invagination and short or blunt roots were significantly more prevalent in females than in males. Implications for orthodontic treatment planning are discussed. PMID- 9973709 TI - Root morphology of the maxillary first premolar in Singaporeans. AB - Extracted teeth were collected from clinical procedures performed in the Faculty of Dentistry, National University of Singapore. A selected sample of 957 maxillary first premolars were subjected to visual examination and digital radiography. There was a higher incidence of two-root form (50.6 per cent) than previously reported for the Singaporean dentition. In the two-root category, 307 teeth exhibited the fused-root form (two fused roots with two root canals) and 177 were distinctively of the two-root form (two separate roots with two root canals and two foramina). The fused-root form was emphasized as an entity in this study. The one-root form accounted for 49.4 per cent. No three-root form was detected. PMID- 9973710 TI - Pain description and severity of chronic orofacial pain conditions. AB - A multidisciplinary pain centre study of 120 consecutive chronic orofacial pain patients assessed pain description and intensity ratings, gender differences, prevalence of concurrent conditions, and interinstrument relationships of the McGill Pain Questionnaire and visual analogue scale. Pain words chosen by patients to describe conditions were predominantly sensory words, and patients with concurrent conditions often listed words indicating a substantial affective component. Results showed pain intensity ratings of chronic orofacial pain conditions have similar or higher pain ratings when compared with other medical chronic pain conditions such as back pain, cancer pain and arthritis. There was a significantly higher female: male ratio (88:32) with gender playing an important but poorly understood causal role. The most frequent condition diagnosed was atypical facial pain (n = 40), followed by temporomandibular disorder (n = 32), atypical odontalgia (n = 29) and pathology of the orofacial region (n = 19). Temporomandibular disorder was present in 75 of the 120 subjects, as the sole pain complaint (n = 32) or as an associated secondary condition (n = 43), indicating concurrent pain conditions exist and may be related. There were significantly higher total pain scores of the McGill Pain Questionnaire in patients with multiple conditions compared with patients with a single condition. The visual analogue scale showed a significant correlation to the number of words chosen index of the McGill Pain Questionnaire for orofacial pain. PMID- 9973711 TI - Service-mix in general dental practice in Japan: a survey in a suburban area. AB - Overseas investigations have reported the amount and variety of dental services provided. An understanding of the current service-mix in private general practice is important in the anticipation of the future practice of dentistry. The main purpose of this study was to describe the service-mix of private general practitioners in Japan, which was recorded using the Australian Dental Association Dental Procedure Code. Some comparisons with previous studies were offered. The youngest age group and adolescents formed only a small percentage of the total patients, while the greatest percentage of patients occurred in the 45 64 year age group. The services provided were mainly restorative, diagnostic advanced restorative and endodontic services. Preventive services represented a minority of dental activity, especially for young patients. Periodontic and orthodontic services were also remarkable for their low percentage in all age groups. In comparison with an Australian study, the percentage of preventive services was considerably lower. Movement toward a preventive emphasis in Japanese dentistry requires a change in the clinical model, de-emphasizing biomedical and aetiological approaches and placing greater emphasis on the patient and factors affecting dental practice. PMID- 9973712 TI - Determination of gold alloy loss during the production of cast dental restorations. AB - Values for the loss of high gold content dental alloy during the fabrication of three types of cast dental restorations were determined. The mass changes measured were for the melting, casting and cleaning processes and the docking and laboratory finishing procedures involved in producing the final restoration. The casting yield from the alloy cast was also determined. Five Brisbane dental laboratories participated and 407 cast restorations were assessed. The mean mass loss for the melting and casting process was 0.109 g (SD 0.326) per cast restoration, and 0.827 per cent (SD 1.805) of the total mass of alloy melted. The data were analysed in four categories: alloy crowns, metal-ceramic crowns, metal ceramic bridges, and combined. The mean total mass loss per restoration from docking and finishing for each of the four groups of cast dental restorations examined was 0.329 g, 0.350 g, 0.927 g and 0.363 g; 13.11, 28.30, 22.07 and 22.18 as a per cent of the mass of the docked casting respectively. The yield of casting masses from the alloy cast were 19.97, 9.11, 29.10 and 13.71 per cent respectively, with all differences significant at the 0.001 level. These values indicate that the recommendation for 50 per cent addition of new alloy for each cast is impractical. The wide spread of the data precludes the establishment of a precise agreed value between dentists and technicians for expected loss. However, the use of the median or mean would provide a value which might be an equitable indicator in the long term. Alternatively, working values can be developed for individual dentist/technician partnerships. PMID- 9973713 TI - Abnormally high fluoride levels in commercial preparations of 40 per cent silver fluoride solution: contraindications for use in children. AB - Although a 40 per cent solution of silver fluoride would be expected to contain 6 per cent fluoride (60,000 ppm), F-levels of 100,000 ppm and 120,000 ppm were found in 14 commercial samples analysed at The University of Western Australia in 1993 and 1994. To determine whether F-levels in 40 per cent AgF preparations have remained high, the present investigation was aimed at analysing different batches of commercial preparations obtained more recently. Fluoride ion analysis was carried out on 24 AgF samples using the Ion-Selective Electrode technique. Independent analyses of the same samples were carried out by a private chemical testing laboratory (Genalysis). Ten samples supplied by Agson Chemical Export were found to contain between 75,000 and 100,000 ppm F-: Genalysis reported 80,000 to 120,000 ppm. Fourteen samples supplied by Southern Dental Industries were found to contain between 70,000 and 120,000 ppm F-; Genalysis reported 88,000 to 108,000 ppm F-. These results confirm significantly higher than expected F-levels (ANOVA p < 0.05) in commercial preparations of 40 per cent AgF. The solutions tested were found to contain a mixture of ammonium fluoride, sodium or potassium fluoride, and silver fluoride. The additional presence of silver difluoride and hydrofluoric acid resulting from the manufacturing process has been suggested as an explanation for the much higher than expected levels of fluoride ion. In view of possible toxicity of 40 per cent AgF in young children, it is concluded that such a highly concentrated solution should not be used clinically; instead, lower strength AgF solutions should be investigated for their efficacy in caries treatment. PMID- 9973714 TI - Polyvinyl siloxane impression materials: an update on clinical use. AB - Polyvinyl siloxane impression materials have applications in a variety of indirect procedures in prosthodontics and restorative dentistry. Favourable handling properties, good patient acceptance and excellent physical properties have resulted in their popularity in today's practice. In this review, the chemistry and important physical properties of polyvinyl siloxanes are summarized, and recent clinical questions of improved hydrophilics, tray adhesives, disinfection, and glove-induced polymerization inhibition are addressed. PMID- 9973715 TI - The old order changeth... PMID- 9973716 TI - Leaking gloves. PMID- 9973717 TI - Further report on dens evaginatus on wisdom teeth. PMID- 9973718 TI - Cracked tooth syndrome. PMID- 9973719 TI - Anaphylactic reactions to local anaesthetic agents. PMID- 9973720 TI - Use of acupuncture in dentistry. PMID- 9973721 TI - Inequalities in health--"it's the poor wot gets the blame". PMID- 9973722 TI - Service reviews in the Community Dental Service. Regional guidance produced by dental services managers and consultants in dental public health in the north west of England. PMID- 9973723 TI - Health years equivalents as a measurement of preferences for dental interventions. AB - OBJECTIVE: To test the feasibility and importance of measuring preferences among treatment choices using Healthy Years Equivalents (HYE). DESIGN: Development of scenarios for alternative approaches to caries treatment. Completion of category rating and standard gamble questions elicited in personal interviews. SETTING: The provision of dental care to children in a public-funded dental health clinic. PARTICIPANTS: Random sample of the adult population of Hamilton, Ontario. MAIN OUTCOME MEASURES: The percentage of the sample unable to complete the interviews, time taken to perform interviews, ease of understanding of interviews, correlation between rank ordering and HYE scores. RESULTS: Ninety-six per cent of the sample were able to complete the HYE exercise. Inconsistencies between HYE scores and rank orders implying preference reversal occurred in 6% of those completing HYE scores for the two scenarios. The additional time taken by the HYE was of the order of 17 minutes but increased with the age of the subject. Where problems occurred, they were related to the method of measurement or the sensitivity of the chosen scale as opposed to additional requirements of the HYE. There was some evidence that HYEs and QALYs produced different scores even in the context of chronic constant health states. CONCLUSIONS: HYEs are a feasible and important practical method of measuring preferences among interventions. Alternative utility-based approaches, such as willingness to pay, may be required to detect differences in modest improvements in temporary health states. PMID- 9973724 TI - Oral health systems in Europe. Part II: The dental workforce. AB - OBJECTIVE: To describe and compare the practice of dentistry and the dental workforce in eighteen European countries. BASIC RESEARCH DESIGN: Semi-structured, in-depth validation interviews were carried out with key-informants from the main national dental associations of EU and associated countries. The interviews were structured around the responses to a previously completed questionnaire, whose topics and terminology had been agreed in advance with the collaborating associations. The resulting descriptions of dental practice and the dental workforce in each country were returned for further validation and correction by the collaborating associations. Ultimate editorial control over the review of each country's oral health system rested with the academic unit from which the associations jointly commissioned the study. RESULTS AND CONCLUSIONS: With the exception of Austria the primary training and registration of dentists is now more or less standard across Europe. However, wide international variation exists in the official recognition of dental specialists and auxiliaries. The Nordic countries of Sweden, Finland and Iceland recognise the broadest range of specialties. In contrast Spain, Portugal, Luxembourg and Belgium currently do not formally recognise any types of specialist practice. Fee-for-service is the dominant form of remuneration for dentists across Europe, but considerable variation exists in the level of fees, how they are decided and the proportion paid by the patient. When based upon standard questionnaires, semi-structured interviews with key informants are an effective method for capturing both the specifics of how an oral health system works, and the general similarities and differences between countries. PMID- 9973725 TI - Relationship between the care index and mean dmft/DMFT. AB - OBJECTIVE: To assess the relationship between the care index and the mean dmft/DMFT in different populations of 5-, 12- and 14-year old children. DESIGN: Information from recent studies of 5-, 12- and 14-year old children, co-ordinated by the British Association for the Study of Community Dentistry (BASCD) was used. The correlation between the mean dmft/DMFT and the care index for each health district was calculated for each age group, along with the linear regression equation of the care index in terms of dmft/DMFT. RESULTS: All the correlation coefficients were negative indicating that the care index would be expected to increase as the disease levels decrease. For the 5-year-old children in 1995/96 three other factors for the same time period; dentist:population ratio, percent of children registered and standardised mortality ratio (SMR), were also included in the model. This did not change the negative relationship between dmft and the care index. CONCLUSIONS: The strong negative relationship between the care index and mean dmft/DMFT levels indicated that in a situation where disease levels are reducing over time, the care index would be expected to increase. Conversely in a situation where disease levels were increasing the care index would be expected to fall. PMID- 9973726 TI - Clinical judgement as a basis for choice of recall interval in child dental care? AB - OBJECTIVE: Extending recall intervals can be an important strategy for making children's dental care more efficient. The purpose of this study was to describe the recall intervals that the clinicians decided were appropriate for children and adolescents when they were instructed to extend and individualise the routines based on clinical judgement. In addition, the effect on recall interval of the profession of the clinician (dentist or dental hygienist), the child's age and the need for fillings were studied. DESIGN: In a four week period in 1995, all dentists and dental hygienists in one county in Norway reported recall intervals for 2,513 children aged 3 to 18 years. RESULTS: The mean current interval since the previous examination was 17.1 months (SD = 4.7 months) and the mean proposed interval until the next examination was 16.4 months (SD = 4.4 months). Approximately 50% of children were evaluated by the clinicians to be suitable for recall intervals of 20 months or more and 10% were assessed as requiring a new examination within 12 months. The length of the current recall interval, the age of the child, whether or not the child received fillings, and whether the decision-maker was a dentist or a dental hygienist were statistically significantly associated with the length of the proposed recall interval. CONCLUSIONS: Basing recall intervals on clinical judgement resulted in intervals longer than 12 months for the majority of the children. PMID- 9973727 TI - Oral health profile of schoolchildren, mothers and schoolteachers in Zanzibar. AB - OBJECTIVE: To analyse oral health status and oral health practices of schoolchildren in Zanzibar, to assess oral health knowledge, attitudes and practices of the mothers, and to describe knowledge and attitudes of schoolteachers in relation to oral health education of children. DESIGN: Cross sectional surveys of standards 1 and 5 children and their mothers were carried out based on the WHO pathfinder principle. The children were clinically examined and the mothers responded to personal interviews. Self-administered questionnaires were used to collect information on a convenience sample of schoolteachers. SETTING: The surveys were conducted to aid the planning and evaluation of school-based oral health promotion in Zanzibar. SUBJECTS: Two hundred and fifty-nine standard 1 and 226 standard 5 children participated in the survey; the sample was balanced by gender and degree of urbanisation. A total of 455 mothers (92% of original sample) and 123 schoolteachers (100% of sample) were included. OUTCOME MEASURES: For children, dental caries experience (dmft/DMFT) and CPI were recorded. For mothers, knowledge about causes and prevention of dental disease, dental attitudes and oral health behaviour were ascertained. For teachers, dental knowledge and attitudes to health education were investigated. RESULTS AND CONCLUSIONS: The mean caries experiences were 2.1 dmft (standard 1) and 0.7 DMFT (standard 5) and the prevalence was higher in urban than in rural areas. Daily toothcleaning was reported for 59% of the children and 67% of the mothers. The use of traditional Miswaki was frequent in rural areas whereas toothbrushes were common in urban areas. The level of knowledge was similar for mothers and teachers. Training in oral health topics is needed for schoolteachers to provide for school-based health education of children. PMID- 9973728 TI - The efficacy and effectiveness of a primary preventive dental programme in non fluoridated areas of Victoria, Australia. AB - OBJECTIVE: To determine the efficacy and effectiveness of a primary preventive dental programme. DESIGN: A field trial comparing an intervention and control group over three years. The intervention group received a preventive programme which consisted of a weekly fluoride mouthrinse (0.2% neutral NaF), an annual application, replacement or repair of pit and fissure sealants, and an annual oral hygiene education programme. The control group received the oral hygiene education programme only. Examinations to record dental caries status were conducted annually for both study groups. SETTING: Five secondary colleges in two non-fluoridated regions of Victoria, Australia. SUBJECTS: 522 subjects aged 12-13 years and considered at high risk of developing dental caries were recruited for the study; 256 received the preventive programme and 266 acted as controls. OUTCOME MEASURES: Dental caries was diagnosed according to World Health Organization criteria. RESULTS: Subjects in the intervention group who completed the three-year preventive programme (efficacy) incurred an average of 1.49 fewer decayed, missing or filled tooth surfaces than the control group. The difference was highly statistically significant. The programme also had a statistically significant impact when analysed by intention-to-treat (effectiveness), even when it was assumed that subjects lost to follow-up received minimal future benefit. Approximately 70% of the improvement in oral health was in the pit and fissure surfaces, with the remainder in the smooth surfaces. CONCLUSION: A comprehensive preventive dental programme introduced into adolescent populations at high risk of developing dental caries can result in significant improvements in their dental health. Further research is required to clarify the public health impact of school-based fluoride mouth rinsing. PMID- 9973729 TI - Orthodontic treatment demand--differences between urban and rural areas. AB - OBJECTIVE: To compare the outcome of orthodontic treatment and the desire for further treatment in 19-year-old young adults treated by specialists in urban and rural areas and to study the influence of the level of education of their parents. DESIGN: The individuals were clinically and retrospectively examined with reference to malocclusions and orthodontic treatment received during childhood and adolescence. SETTING: Orthodontic department in Kronoberg County, Sweden. SUBJECTS: From a sample of 302 young adults, all individuals who had received orthodontic treatment by specialists (n = 60) were selected. OUTCOME MEASURES: The individuals were compared according to outcome of treatment and place of residence. The pre-treatment need, the residual treatment need, the treatment results, and the desire for further treatment were estimated as well as treatment duration, number of visits, percentages of discontinued treatments and parents' level of education. RESULTS: There was a higher frequency of individuals without previous treatment and a lower frequency of specialist-treated individuals in rural areas than in urban areas in the county. The treatments implied substantial improvements, with a higher reduction of treatment need and a higher degree of success in patients from urban areas than from rural areas (P < 0.01). There were no statistically significant differences according to gender, socio-economic factors, or desire for further treatment. CONCLUSIONS: The results suggest a greater degree of tolerance towards malocclusions in individuals in rural areas than in urban areas. PMID- 9973730 TI - Permanent tooth loss among adults and children in Saudi Arabia. AB - OBJECTIVE: The objective of this study was to assess tooth loss among various age groups in Saudi Arabia as a part of a national epidemiological study on oral conditions. DESIGN: Methodology was based on the WHO International Collaborative Study II. The sampling strategy covered Kingdom-wide sites in 10 regions with stratified cluster random samples. Data collection was confined to age-groups 6 to 7, 12 to 13, 15 to 19, 20 to 29, 35 to 44 and 65 to 74 years. SETTING: Children and adults from the schools and households of the ten provinces of Saudi Arabia. Clinical examinations were performed in daylight to determine oral clinical status and the prevalence of tooth loss. SUBJECTS: A total of 7,377 children and adults in the specified age-groups. OUTCOME MEASURES: Loss of permanent teeth assumed due to caries, assessed on clinical examination. Examiners reliability was calibrated using the kappa statistic. RESULTS: Tooth loss due to caries was 0.03 in the 6 to 7-year age-group; 0.12 at 12 to 13 years; 0.29 at 15 to 19 years; 1.24 at 20 to 29 years; 4.15 at 35 to 44 years; and 15.79 in the 65 to 74-year age-group. When compared by gender, a statistically significant difference was found between males and females for those aged 6 to 7, 15 to 19, 20 to 29, and 35 to 44 years. CONCLUSIONS: This study indicated that tooth loss increases with age and differs for gender and socio-economic status. No differences found based on city or rural lifestyles. PMID- 9973731 TI - Dental services for adults with a learning disability: care managers' experiences and opinions. AB - OBJECTIVE: To investigate care managers' experiences in obtaining dental services for their clients. BASIC RESEARCH DESIGN: Descriptive survey collecting qualitative and quantitative data by semi-structured interviews. SETTING: Inner London boroughs of Lambeth, Southwark and Lewisham. PARTICIPANTS: Care managers or their delegated representatives in all homes listed in June 1996 by the registration and inspection units of the boroughs' social services departments, under the Registered Homes Acts (1984; 1991). MAIN OUTCOME MEASURES: Managers' experiences in obtaining dental services for their residents and their perception of their residents' current need for dental treatment. Perceived barriers to care. RESULTS: Managers perceived a current need for dental treatment in 14% of the residents. In 4 out of 80 homes (5%) none of the clients had seen a dentist during the preceding 12 months, but not because homes had been unable to obtain services. The most common reason given by managers was that clients were unwilling to accept care. Continuity of care and partnership between carers and dentists were seen as facilitating co-operation. Eighty five per cent of homes made some use of the Community Dental Services. CONCLUSIONS: Managers perceived that sufficient services were available in the area; the chief barrier to care was residents' reluctance to accept treatment. The Community Dental Service played an important role in the provision of dental services. Managers felt that the treatment of severely disabled patients required special skills and experience. PMID- 9973732 TI - Inequalities in children's caries experience: the nature and size of the UK problem. AB - OBJECTIVE: To discuss, as part of a symposium on 'Dental Care for the Disadvantaged Child', the inequalities in caries experience between a minority of children who demonstrate substantial dental disease and have, as a consequence, a considerable need for dental care and the majority who have little disease. METHOD: 1) Analysing data from regular NHS surveys of the dental health of British children in a number of defined age groups and examining socio-economic factors which operate and influence levels of dental caries to answer questions such as "Do we understand which children need and get appropriate dental care?". 2) Considering how appropriate future needs may be identified and addressed, and the gap between academic acceptance of new methodology and use by dental professionals may be narrowed. CONCLUSIONS: Integrated approaches to prevention should be focused on those children who have the greatest need in addition to the provision of appropriate, clinically effective, preventive and operative care for all children. PMID- 9973733 TI - What has general dental practice got to offer? PMID- 9973734 TI - A practitioners view. PMID- 9973735 TI - The present and future role of the community dental services. PMID- 9973736 TI - The case for secondary and tertiary care by specialist dental services. PMID- 9973737 TI - Dental care of the disadvantaged child--a teacher's point of view. PMID- 9973738 TI - Continuous monitoring of jugular bulb venous oxygen saturation for evaluation of cerebral perfusion during carotid endarterectomy. AB - In this study we examined whether continuous monitoring of jugular bulb venous oxygen saturation (SjO2) is applicable for the evaluation of cerebral hypoperfusion during carotid endarterectomy (CEA). The subjects were 25 patients who underwent elective CEA under general anaesthesia. After the carotid stump pressure (SP) was measured, SjO2 and the somatosensory evoked potentials (SEP) were monitored during the carotid test clamping for 10 min. There was no alteration in cardiovascular and respiratory status during the test clamping. No correlation was observed between SEP amplitude and SP (r = 0.16, p = 0.25). However, at clamping, SjO2 decreased from 70 to 64% (p < 0.01) with a reduction in SEP amplitude from 2.0 to 1.6 microV (p < 0.01). After declamping, SjO2 increased from 65 to 70% (p < 0.01) with a recovery in SEP from 1.6 to 1.9 microV (p < 0.01). The changes in SEP amplitude and SjO2 correlated (r = 0.66, p < 0.001). These results suggest that continuous monitoring of SjO2 is superior to SP measurement in the prediction of cerebral hypoperfusion caused by carotid clamping and applicable to CEA. PMID- 9973739 TI - Short-term effect of correcting leg length discrepancy on performance of a forceful body extension task in young adults. AB - In this study we assessed the short-term effect of correcting leg length discrepancy on a vigorously performed task of resisted full body extension in 10 men, 18 to 35 years old, who had estimated leg length discrepancies of 10-15 mm. Using a cable ergometer we examined work performed, initial peak tension exerted on the ergometer, second peak tension, time to first peak tension, and mean velocity of the whole task. Each subject performed the task both with and without a heel lift, introduced to equalize leg length. The interval between testing under these two conditions was 48 hr. In the task of pulling the cable upward, each subject began from floor level with knees and trunk flexed, progressing to full body extension with the arms pulling the cable overhead with maximal effort. For each trial the task was repeated 15 times, with intervals of 90 seconds between the repetitions. Use of the lift failed to have a statistically significant effect on any of the variables, although it clearly enabled three of the subjects to exert greater strength with the arms and trunk during the second peak tension. This suggests that 1) overall body extension is influenced by too many factors to be affected in a consistently predictable way by a heel lift to correct leg length discrepancy, and 2) the heel lift may aid certain subjects with leg length discrepancy specifically during extension of the trunk in this task. PMID- 9973740 TI - Hepatic resection for cavernous hemangiomas of the liver. AB - In this report, we evaluate the indications of, and present our recent strategy for, cavernous hemangioma of the liver. Seven patients with cavernous hemangiomas of the liver, who underwent hepatic resection were enrolled in this study. The lesions were located in the right lobe in 3 patients, the left lobe in 2, and in both the right and left lobes in 2. The longest diameter of the lesions ranged from 1.4 to 14.5 cm (mean, 8.2 cm). The indications for hepatic resection were symptomatic lesions in 3 patients, lesions suspected to be hepatocellular carcinoma in 2, and symptomatic and growing lesions during follow-up in 2. Right lobectomy was performed in 2 patients, left lobectomy with caudate lobectomy in 1 patient, and minor hepatic resection in the other 4 patients. One of the patients who underwent minor hepatic resection had recently received laparoscopy-assisted hepatic resection and one of the three patients who received transfusion during surgery was given an autotransfusion. There were no mortality, and morbidity was minimal. In conclusion, hepatic resection, including laparoscopy-assisted procedures, was considered a safe treatment. Hepatic resection for cavernous hemangioma should be performed only in patients with moderate to severe symptoms, complicated lesions or both, because most benign lesions have a good natural course. Furthermore, in the future, less invasive surgical procedures should be used whenever possible to treat these benign liver tumors. PMID- 9973741 TI - Percutaneous microwave coagulation therapy for hepatocellular carcinoma. AB - We evaluated the efficacy of percutaneous microwave coagulation therapy (PMCT) as compared with hepatectomy in 19 patients with hepatocellular carcinoma (HCC). In 6 patients with tumors more than 3 cm in diameter, coagulation was inadequate after a single session of PMCT. Patients with multiple tumors had recurrence within 1 year. For single tumors 3 cm or less in diameter, the therapeutic effectiveness of PMCT was comparable to that of hepatectomy in cumulative survival and cancer-free survival rates. We conclude that PMCT should be used in the initial treatment of HCC only in patients with single tumors of up to 3 cm in diameter. Surgical removal is recommended for tumors of more than 3 cm in diameter. PMID- 9973742 TI - A surgically treated long-term survivor of hepatocellular carcinoma with tumor thrombi in the trunk of the portal vein. AB - Prognosis of hepatocellular carcinoma (HCC) patients with tumor thrombi (TT) in the trunk of the portal vein (PV) has been extremely poor. There have been few reports of long-term survivors with such an advanced condition. In this article, the case of a 62-year-old woman of HCC, who survived for 6 years and 9 months after an operation, with TT in the trunk of the PV is described. The patient not only had a primary tumor of 4 cm in diameter with TT but also multiple intrahepatic metastases in the bilateral lobe of the liver. A palliative lateral segmentectomy with tumor thrombectomy through the incised left first branch of the PV was performed. Moreover, an intraoperative ethanol injection for residual intrahepatic metastatic tumors was performed subsequently. Hepatic arterial infusion of anti-cancer drug with Lipiodol, intraportal continuous infusion of 5 FU and percutaneous ethanol injection therapy were performed suitably during the follow-up periods. The patient survived for 6 years and 9 months after operation and died of hepatic insufficiency with cancer. In this case a patient who suffered from HCC with TT in the trunk of the PV was successfully treated by multimodality procedures including hepatic resection with tumor thrombectomy. PMID- 9973743 TI - Laparoscopy-assisted hepatectomy for a large tumor of the liver. AB - We performed a laparoscopy-assisted hepatectomy on a 52-year-old woman with a large hepatic cavernous hemangioma (longest diameter, 8.5 cm). With the use of Pringle's maneuver, the left lateral segment of the liver was resected with a Cavitron ultrasonic surgical aspirator (CUSA) while lifting the abdominal wall. Postoperative hepatic dysfunction was mild and transient, resolving spontaneously early after surgery. We intend to expand the indications of this minimally invasive procedure for hepatic resection. PMID- 9973745 TI - Home births: an unresolved debate. PMID- 9973744 TI - Decreased serum neutral endopeptidase activity in children with bronchial asthma. PMID- 9973746 TI - Sanity and insanity--a personal view. PMID- 9973747 TI - The calcium channel blocker debate. AB - What, finally can we conclude from the work to date regarding the use of CCB's? The large clinical trials here give a number of clear messages to the prescriber. Short-acting dihydropyridine CCB's are unproven as prophylactic agents in ischaemic heart disease. In patients with poor left ventricular function post infarct, CCB's are associated with an unchanged or increased mortality. Use of medications in the treatment of hypertension should be with proven first-line therapeutic agents; beta-blockers, diuretics; and the long-acting dihydropyridine CCB's nifedipine GITS and nitrendipine. The final argument in the discussion over the safety or otherwise of calcium channel blockers will rest in the completion in the future of a number of prospective, randomised, place-controlled clinical drug trials. These trials are currently ongoing, and their results may not be available until after the year 2000. PMID- 9973748 TI - Use of the toxicology emergency laboratory services in common acute poisonings. PMID- 9973749 TI - ACE inhibitors and diabetic retinopathy. PMID- 9973750 TI - The treatment of opiate addiction during pregnancy. PMID- 9973751 TI - Linear IgA disease--a review of four patients. AB - Four cases of Linear IgA Disease (LAD) seen over a five year period are reviewed and our most recent LAD patient is described in detail. We summarise data on our patients and outline clinicopathologic features, aetiology and management of this unusual but important condition. PMID- 9973752 TI - How much of a general practitioner's prescribing is outside his/her control? AB - OBJECTIVE: To analyse and quantify that portion of one General Practioner's prescribing that is outside his/her control. DESIGN: Detailed analysis of one General Practioner's General Medical Services prescribing over a three month period during 1996. SETTING: A Group Practice in Sligo, Ireland. MAIN OUTCOME MEASURES: The number and cost of items outside the General Practitioner's control expressed as a percentage of his total General Medical Services prescribing. The source of these items, and whether they are newly prescribed items or not. RESULTS: 12.8% numerically and 23.8%, costwise, of items prescribed by one GMS General Practitioner were found to be outside his control. Of these items, psychiatric outpatient consultations and medical in-patient discharges account for 22.8% and 18.4% numerically, respectively, and 25.7% and 22.6% costwise, respectively of the total numbers of items and costs outside his control. CONCLUSIONS: A relatively small proportion of items of a General Practitioners prescribing accounting for a disproportionately large amount of the costs are outside his control. PMID- 9973753 TI - A descriptive study of drug therapy and cost for elderly residents in a nursing home. AB - Drug therapy for 115 patients in Health Board contracted beds in a long-stay institution for the elderly were studied. The results were analysed for frequency, type and cost of medicines. 96.5% of patients received a total of 473 routine medicines, an average of 4.1 medicines per patient, females received a higher number of medicines than males. The average cost per person per day was 67.6p for all medicines. The most frequently prescribed medicines were for therapeutic groups CNS (32.3%) CVS (17.8%) and GIS (14.2%). PMID- 9973754 TI - A study of self-care among Irish doctors. AB - Little is known about the self care employed by Irish doctors, though studies in other countries suggest this is likely to be less than ideal. In this study 76 doctors; general practitioner trainees, general practitioners and hospital consultants, completed a questionnaire on their self management of illness. High levels of self-prescribing and referral were discovered. The implications for the health of doctors in Ireland and the need for an occupational health service for doctors are discussed. PMID- 9973755 TI - Hyponatraemia, seizures and stupor associated with ecstasy ingestion in a female. PMID- 9973756 TI - Patient access to medical records. PMID- 9973757 TI - An evaluation of the CAGE questionnaire in an elderly psychiatrically ill population. PMID- 9973758 TI - A role for dopexamine hydrochloride in septic shock. PMID- 9973759 TI - Massive dilation of the urinary tract secondary to familial cranial diabetes insipidus. PMID- 9973760 TI - Geriatric dental care crisis. PMID- 9973761 TI - Latex allergy. PMID- 9973762 TI - World AIDS Day. PMID- 9973763 TI - The law and ethics in relation to dentists treating HIV-positive patients: report on a recent U.S. Supreme Court case. AB - The U.S. Supreme Court confirms that an HIV-seropositive patient is a "handicapped" person even if totally asymptomatic. Hence, the patient is illegally discriminated against if a dentist consequently refuses to treat the person in the same manner in which he or she treats other patients. Canadian dental care providers should be aware of this decision, because it is reasonable to expect that the high-level Canadian courts and the Supreme Court of Canada would follow this U.S. Supreme Court decision. In addition, the U.S. judgment in effect supports judgments in recent Canadian lower court cases. PMID- 9973764 TI - [Le Fort I surgery, sagittal osteotomy and genioplasty and their impact on the temporomandibular joint]. AB - Dentofacial deformities of the jaws, teeth and middle and lower thirds of the face affect both function and appearance. Epidemiological studies show that many Americans suffer from a malocclusion, which alters the proportions of the face. Moreover, in about 5 per cent of cases, the deformity is great enough to cause a severe handicap. A number of years ago, only orthodontic therapy was available, its aim being to achieve an acceptable occlusal relation while improving appearance as much as possible. However, this therapy provided limited improvement. Consequently, serious cases were later treated surgically. Since the 1970s, new surgical techniques have made it possible to reposition the jaws or dentoalveolar segments. As a result, today many more cases are treated in collaboration with orthodontists and surgeons. This article summarizes the main orthognathic surgical techniques, their procedures and their effects on temporomandibular disorders. PMID- 9973765 TI - The case for a strong anti-tobacco lobby by the CDA--if not now, when, and if not us, who? PMID- 9973766 TI - Exposure or absorption and the crucial question of limits for mercury. AB - Health Canada recently lowered the recommended maximum daily exposure of mercury from all sources for women of child-bearing age and for children less than 10 years. This new exposure guideline does not seem to be based on any new scientific finding of human toxicity. The average daily intake of methylmercury (mainly from fish) that may cause demonstrable health effects in the most sensitive individual is 300 micrograms/day, or 4.3 micrograms Hg/day/kg body weight. The new, lower Health Canada limit is 95% below the level that may cause health effects. A number of studies have looked at methylmercury in human breast milk (where maternal consumption of fish is high), but no strong evidence of toxicity has been reported. The amount of mercury released from dental amalgam is minimal; a person would have to have 490 amalgam surfaces for there to be enough mercury vapour and ionic mercury given off from amalgam fillings to meet the maximum exposure guidelines. The uptake of food-related organic mercury is six times higher than the uptake of mercury from amalgam; moreover, food-related mercury is significantly more toxic. Many studies of amalgam-related mercury are flawed by confusion between exposure and absorption for the various forms of mercury, a limited selection of data, the ignoring of confounding variables or the misclassification of data. PMID- 9973767 TI - The TMD controversies continue. PMID- 9973768 TI - Bilateral dentigerous cysts--report of an unusual case and review of the literature. AB - Dentigerous cysts are the most common developmental cysts of the jaws, most frequently associated with impacted mandibular third molar teeth. Bilateral dentigerous cysts are rare and occur typically in association with a developmental syndrome. The reported occurrence of bilateral dentigerous cysts in the absence of a syndrome is rare and, to date, only 11 cases have been described. Here, we report a case of bilateral nonsyndromic, dentigerous cysts and review the literature for this unusual finding. PMID- 9973769 TI - Effects of ascorbic acid and carbohydrate ingestion on exercise induced oxidative stress. AB - BACKGROUND: We studied the effects of supplementation of vitamin C and carbohydrate on acute exercise-induced lipid peroxidation. METHODS: EXPERIMENTAL DESIGN: two randomized controlled trials. PARTICIPANTS: 17 endurance athletes. INTERVENTIONS: in study I, nine athletes repeated twice a 10.5-km maximal run and ingested in a randomized single-blind order either 2.0 g vitamin C or placebo. In study II, eight athletes repeated twice a 27-km maximal run and ingested in randomly either 105 g carbohydrate or placebo. Venous blood samples were taken before the exercise, immediately after the exercise, and after a recovery period of 90 min (study I) or 120 min (study II). MEASURE: serum diene conjugation, lipid peroxidation. RESULTS: In study I, there was no difference in serum diene conjugation between the trials during exercise (pre- vs post-exercise). However, during the recovery period (post-exercise vs recovery sample) serum diene conjugation concentration decreased by 11% in the vitamin C trial but not in placebo (p = 0.028). In study II, there was no difference between the carbohydrate and placebo trials. CONCLUSIONS: Vitamin C and carbohydrate do not prevent exercise-induced increase in oxidative stress, but vitamin C, being a potent aqueous antioxidant, seems to decrease the levels of diene conjugation during recovery after exercise. The clinical significance of this phenomenon needs further evaluation. PMID- 9973770 TI - Maximal power and force-velocity relationships during cycling and cranking exercises in volleyball players. Correlation with the vertical jump test. AB - BACKGROUND: The aim of this study was to propose a test battery adjusted to volleyball players and to study the links between dynamic (vertical jump, force velocity relationships and maximal anaerobic power in cranking and cycling) and static (maximal voluntary force and rate of force development in isometric conditions) performances. METHODS: The relationships between braking force (F) and peak velocity (V) have been determined for cycling and cranking exercises in 18 male volleyball players of a district league. According to previous studies, these F-V relationships were assumed to be linear and were expressed as follows: V = V0(1-F/F0), where V0 should be an estimate of the maximal velocity at zero braking force whereas F0 is assumed to be a braking force corresponding to zero velocity. Maximal anaerobic power in cycling (Pmax leg) and cranking (Pmax arm) were calculated as equal to 0.25 V0F0. The same subjects performed a vertical jump test (VJ) and a strength test on an isometric leg press with the measurement of the unilateral isometric maximal voluntary force (MVF) and indices of rate of isometric force development (RFD): maximal rate of force development (MRFD) and the time from 25% to 50% of MVF (T25-50). RESULTS: Pmax leg (15.8 +/- 1.4 W.kg-1) and V0 arm (259.6 +/- 13.1 rpm) were high but similar to the results of elite athletes, previously collected with the same protocols and the same devices. VJ was significantly with F0 leg, Pmax leg and Pmax arm related to body mass. The performances of the dynamic tests were significantly correlated and especially the parameters (V0, F0, Pmax) of the force velocity tests in cycling were significantly correlated with the same parameters in cranking. The results of the isometric tests (MVF, MRFD) were not correlated with VJ, except T25-50 of the left leg. CONCLUSIONS: A vertical jump test and a force velocity test with the arms are proposed for a test battery in volleyball players. PMID- 9973771 TI - Physical training of football players based on their positional rules in the team. Effects on performance-related factors. AB - BACKGROUND: The aim of this study was to evaluate the relative effectiveness of an individualized training programme for football players according to their positions in the team, by comparing it with a programme which did not differentiate roles, but utilized the same means for training. METHODS: Forty four young top level football players divided equally into an experimental and a control group were submitted to two different training programmes for an 8-month period. Each group consisted of 5 forwards, 6 midfielders, 4 fullbacks, 4 centerbacks and 3 goalkeepers. The two groups had almost the same average age (17.8 +/- 0.6 and 17.7 +/- 0.6 yrs respectively), weight (72.6 +/- 4.7 and 72.8 +/- 3.7 kg) and height (181.3 +/- 4.4 and 180.3 +/- 4.0 cm). The following measurements were taken before and after the training period in order to evaluate the aerobic and anaerobic (lactacid and alactacid) power as well as explosive and elastic power which are related to football performance: running tests of 30, 50, 300 and 1,000 meters, squat jump (SJ), counter movement jump (CMJ) and repetition counter movement jump (test 15"). RESULTS: A percent improvement observed for forwards and centerbacks was significant, in comparison with the control group, in all tests but the 30 and 1,000 meters run, on the contrary fullbacks and midfielders demonstrated a significant improvement only in the 1000 m run test (p < 0.01). In addition, a significant increase (14%, p < 0.01) was observed in CMJ of goalkeepers in the experimental group, in comparison with the control group. CONCLUSIONS: It is concluded that individualized training developed in accordance with the real model of football performance and the different mechanisms of bioenergetic processes, is a superior method of training and can optimise the performance of all player in the team. PMID- 9973772 TI - Effect of summer intermission on skeletal muscle of adolescent soccer players. AB - BACKGROUND: To study the effect of some weeks of rest on three groups of adolescent soccer players, who had undergone systematic training for eleven months. METHODS: EXPERIMENTAL DESIGN: Retrospective and comparative investigation; duration 4-8 weeks. SETTING: young amateur players from a Spanish football club were examined at the beginning and at the end of the summer rest period. PARTICIPANTS: 37 young soccer players aged 14, 15 and 16 years old. They were members of three football teams. INTERVENTIONS: during the rest period they were free from any training program. MEASURES: biopsies of M. vastus lateralis were taken immediately after training and after the summer holidays. The type, percentage and diameter of the fibers, as well as the enzymes of glycogen metabolism (glycogen synthase and glycogen phosphorylase), glycolysis (phosphofructokinase and lactate dehydrogenase), oxidative metabolism (succinate dehydrogenase and citrate synthase) and creatine kinase and transaminase (aspartate and alanine aminotransferase) were studied. RESULTS: Detraining had an adaptation effect, decreasing the cross-sectional area of type I and type II fibers, and decreasing the activities of creatine kinase, citrate synthase, phosphofructokinase, lactate dehydrogenase and aspartate aminotransferase. CONCLUSIONS: The results can help trainers to plan the length of the rest period between training. PMID- 9973773 TI - Morphological and performance characteristics as drop-out indicators in female gymnasts. AB - BACKGROUND: Aim of this study was to investigate if morphological and performance characteristics are significant indicators to predict drop-out in female gymnasts. METHODS: EXPERIMENTAL DESIGN: comparative investigation between two groups of female gymnasts at the start of a 3-year follow-up period. SETTING: participants of the study came from two gymnastic clubs from the Antwerp region in Flanders, Belgium. PARTICIPANTS: in total, 81 female competitive gymnasts (mean age: 10.5 + 2.6 years) were investigated, of which 46 were continuing gymnasts, while 35 dropped-out from the sport during the following 3 years. MEASURES: included were a large battery of a anthropometric characteristics, skeletal maturation, physical fitness tests, and gymnastic-specific strength and flexibility tests. Differences between the two groups were analysed by means of the t-test and analysis of co-variance with chronological age as the co-variate. RESULTS: Compared to the gymnasts, the drop-outs were significant (p < 0.01) older (11.3 and 9.7 years respectively), more mature (skeletal ages are 10.6 and 9.4 years respectively), taller (143.5 cm and 135.2 cm respectively), and heavier (36.0 kg and 29.4 kg respectively). Also for almost all other anthropometric dimensions, gymnasts were significantly (p < 0.01) smaller than the drop-outs, except for the biceps, triceps, medial calf, and thigh skinfolds. Concerning the fitness and gymnastic-specific test characteristics, the drop-outs performed also significantly (p < 0.01) better than the continuing gymnasts. The ANCOVA analysis, however, revealed that it was mainly the age factor that distinguished both groups. After controlling for chronological age, no differences between both groups could be demonstrated for almost all anthropometric and performance characteristics with the exception for upperarm circumference flexed, calf circumference, and biceps skinfold. For these variables, drop-outs showed still significant (p < 0.05) higher values compared to the gymnast's group. CONCLUSIONS: Based on these findings, it is concluded that factors related to the physical make-up and performance capacities of our gymnasts under study are minor indicators for the withdrawal from competitive gymnastics, and it is hypothesized that the social and psychological factors associated with the older age of the drop-out girls are presumably more important. PMID- 9973774 TI - Exercise without dietary restriction as a means to long-term fat loss in the obese cardiac patient. AB - BACKGROUND: To examine the effects of a 12-month daily walking program without dietary restriction on the metabolic rate, body composition and blood lipid profile of overweight and moderately obese patients following myocardial infarction. METHODS: DESIGN: longitudinal training (preliminary study). SETTING: out-patient cardiac rehabilitation program. PARTICIPANTS: twelve consecutive volunteers (8M, 4F) with a body mass index of 25-40 kg/m2. Relative to average cardiac patients, the men but not the women were significantly heavier (100.8 vs 77.4 kg [M], 70.7 vs 74.2 kg [F]) and fatter (hydrostatic estimate of body fat 34.0% vs 23.1% [M]; 38.3% vs 36.3% [F]) than the general cardiac patient. MEASURES: body mass, hydrostatic weighing, triglycerides, total, HDL- and LDL cholesterol, resting and peak oxygen intake, one week food intake diaries. RESULTS: Daily walking increased progressively from 20 min to 43 min over 3 months, and was then held constant for 9 months. Peak aerobic power increased 24%, from 19.9 to 24.6 ml/[kg.min] (p < 0.001). Resting oxygen intake rose from 3.1 to 3.4 ml/[kg.min], (p < 0.05). Energy intake increased from 6.10 to 6.57 MJ/day, but body mass decreased by an average of 4.5 kg (p < 0.05, 4.1 kg [M], 5.1 kg [F]), and body fat content diminished from 35.4 to 33.2% (p < 0.02, 1.8% [M], 3.2% [F]), with no change in lean body mass (57.7 vs 57.8 kg). Triglycerides diminished from 2.63 to 2.28 mmol/L (p < 0.005). Total and LDL-cholesterol also tended to change favorably (from 6.15 to 5.80 and 4.44 to 3.80 mmol/L respectively, but HDL-cholesterol was unchanged). CONCLUSIONS: A daily walking program without dietary restriction induces a favorable change in body composition and lipid profile in moderately obese cardiac patients. An exercise induced increase of resting metabolism apparently makes an important contribution to this outcome. PMID- 9973776 TI - The cardiovascular responses of male subjects to kung fu techniques. Expert/novice paradigm. AB - BACKGROUND: The primary aim was to assess cardiovascular responses of expert and novice subjects to kung fu techniques. It was hypothesised that experienced subjects would demonstrate improved economy of movement during the techniques, evidenced by reduced exercise intensity. METHODS: EXPERIMENTAL DESIGN: a comparative design was established utilising two groups; experienced (group E), and novice (group N). SETTING: the experimentation took place under laboratory conditions, but was designed to maximise external validity. PARTICIPANTS: the only preselection variables were regular attendance at training and experience. Nine experienced males (group E, exp 9.5 +/- 5.2 yrs) and nine novice males (group N, exp 1.2 +/- 0.1 yrs) participated. The only exclusion guidelines were contraindications to participate within a maximal test, no subjects were excluded upon this basis. INTERVENTIONS: N/A. MEASURES: each subject participated in three kung fu protocols (forms, kicking and punching). Each protocol, randomly allocated, consisted of ten work (30 sec) and ten rest periods (30 sec). MEASURES taken during the protocols were heart rate (HR) and oxygen consumption (VO2). These were expressed as a percentage of maximal values to reflect exercise intensity. RESULTS: During both the form protocol and punching protocol group E were found to be working at a significantly (p < 0.05) lower % VO2 max than group N (forms--group E = 71.5 +/- 5.3, group N = 82.1 +/- 6.1; punching--group E = 37.5 +/- 2.1, group N = 40.6 +/- 2.6, p < 0.05). This suggests that experienced subjects were more economical when performing similar movement patterns. CONCLUSIONS: It was concluded that cardiovascular responses to kung fu techniques differ depending upon experience level. It is difficult to directly relate this to improved economy since work output could not be accurately quantified. It was also found that kung fu protocols elicited exercise intensity into the cardiovascular training zone. PMID- 9973775 TI - Cardiovascular stress and lactate formation during gymnastic routines. AB - BACKGROUND: Carried out to investigate cardiovascular and metabolic response during various gymnastic routines [Pommel Horse (PH), Roman Ring (RR), Parallel Bar (PB), Horizontal Bar (HB) and Floor Exercise (FE)]. METHODS: EXPERIMENTAL DESIGN: comparative and randomized. SETTING: General purpose, applicable on gymnastics training. Participants. Five male volunteers drawn from students attending sports coaching course in gymnastics at NIB, Patiala. A mixed population from all over India who had competitive experience of 6 to 10 years. INTERVENTIONS: no interventions. MEASURES: presence of heart rate overshooting, high lactate levels and individual characteristics of the gymnastics routines. RESULTS: In all the routines peak HR was much lower than maximum heart rate (HRmax) of the gymnasts. Mean HR was lowest in first set and highest in the final (3rd set) on all the apparatuses. Highest mean HR was recorded in HB followed by FE, RR, PB and PH respectively. After both first and third sets blood lactic acid (La) was highest in FE followed by RR, PB, HB and PH. La levels following the first set were 7.11, 6.77, 6.23, 5.97 and 5.18 mM/l, respectively. Third set values were 10.54, 10.16, 8.95, 8.74 and 8.04 mM/l. CONCLUSIONS: (a) Cardiovascular load in various gymnastic routines is considerably less than maximal running; (b) HR overshoot is common at the end of all the men's gymnastic routines; training evaluation or performance evaluation in gymnastics through heart rate should consider this fact to avoid any misinterpretation; (c) PH is physiologically least demanding among the five while FE and RR are most stressful; (d) repetition of gymnastic exercise routines with short rest pause may lead the gymnast to reach nearer to his lactate tolerance; (e) gymnastics activity is dominated by anaerobic metabolism. PMID- 9973777 TI - Isokinetic testing of flexor and extensor muscles in athletes suffering from low back pain. AB - BACKGROUND: The aim of the study was to verify the usefulness of isokinetic testing in athletes with chronic low back pain (LBP) to obtain quantitative information for rehabilitation purposes. METHODS: EXPERIMENTAL DESIGN: a comparative study. SETTING: Physiotherapy Department--Institute of Sports Medicine in Italy. PARTICIPANTS: 50 men, aged 25-65, practising running, cycling, triathlon, tennis, soccer, basketball, volleyball, skiing and golf. The patients were divided into two groups. Group A was treated for 3 months with postural exercises 2 or 3 times a week. Group B was treated for the same period of time with resistive exercises performed by resorting to specific machines. MEASUREMENTS: Before and after treatment, trunk muscle strength was evaluated by means of an isokinetic test carried out in a seated position. The isokinetic measurements used were peak torque (PT), work, power-in the best repetition and total work (TW) in four repetitions. Both the pain and the functional impairment during physical activity was evaluated by subjective visual analogic scale. RESULTS: The PT showed a parallel increase in flexor and extensor muscles in Group A. In Group B it increased by 32.2% at 60 degrees/s and 44.1% at 120 degrees/s as for the extensor muscles while the flexion-to-extension ratio decreased significantly. The TW registered a bigger percentage increase in both groups (+21% at 60 degrees/s and +20.4% at 120 degrees/s in Group A; +36.5% at 60 degrees/s and +50.3% at 120 degrees/s in Group B). CONCLUSIONS: The two rehabilitation programmes had the same effect on the course of LBP, but in Group B we observed a bigger increase in strength which could be potentially useful during a sports activity. PMID- 9973778 TI - Back injuries in competitive squash players. AB - BACKGROUND: The aim of this investigation was to examine the prevalence of back injuries in competitive squash players. METHODS: EXPERIMENTAL DESIGN: a retrospective analysis was made using a cross-section of current competitive squash players (survivor population). SETTING/PARTICIPANTS: an attempt was made to distribute a questionnaire on back injuries to all competitive squash players registered in the Otago provincial area, New Zealand, (n = 1047), of which 495 questionnaires were returned (47.3% compliance). INTERVENTIONS: variables were cross-tabulated and analysed via descriptive statistics, paired t-tests, chi analyses of trend and chi 2 tests of significance. MEASURES: the questionnaire obtained information on demographics, the level of play (ability), overall volume of play (average frequency and duration of all exposures), plus the occurrence and severity of back injury. RESULTS: Nearly 52% of the sample reported they had suffered back injury. Of these, 33.5% claimed squash initiated their injury, 20.6% claimed squash exacerbated a previous back injury and the remaining 45.9% felt that squash had no detrimental effect on their back injury. Significantly higher frequencies of back injury were observed in males (56.5% compared to 46.4% in females, p = 0.033), in players of higher grade (p = 0.006),and with increased frequency (p = 0.01), but not duration of play (p = 1.0). CONCLUSIONS: These results suggest that the greater activity and possible over-reaching for the ball associated with higher levels of play may increase the risk of back injury and provides tentative support for the notion that back injuries in squash players might be related to periods of relative over-use. PMID- 9973779 TI - Can emotive imagery aid in tolerating exertion efficiently? AB - BACKGROUND: The study examined the role of relaxation and aggressive types of imagery and the effect of goal orientations, self efficacy, self control, and determination on exertion tolerance. METHODS: EXPERIMENTAL DESIGN: the participants underwent an exertive task in which they were required to squeeze a dynamometer, at 50% of their maximal hand-grip capacity, for as long as they could. Perceived exertion was measured every 15 sec during the task. The time that elapsed between rating exertion as "strong", and dropping the handbar under 10% of the designated 50% criterion, was considered as the "zone of exertion tolerance". PARTICIPANTS: forty-eight female university students were randomly assigned into 3 groups. INTERVENTIONS: two imagery techniques, one under relaxing and one under aggressive conditions were taught and then applied. In the control condition, discussions were conducted. MEASURES: traits such as goal orientation (task and ego), physical self-efficacy and self-control were measured prior to performing the task, while rate of perceived exertion task-specific determination (i.e., task-related confidence, commitment, exertion tolerance, and effort investment) were measured before, during and after the task. RESULTS: The results showed an average of 31% and 28% increase in exertion tolerance in participants who used aggressive and relaxation imagery techniques respectively, compared to 4% reduction in the controls. RM ANOVA indicated equality between the two imagery groups but both were significantly different from the control group. Physical self-efficacy, self-control, and task-specific determination were found nonsignificant, but their important roles in coping with aversive stimuli are highlighted. It was evident that the "coping" mechanism rather than the "distraction" mechanism accounted for the larger sustain in the "zone of exertion tolerance". CONCLUSIONS: Imagery can be used efficiently in exertion tolerance but more studies are needed on athletes. PMID- 9973780 TI - Brachytherapy in early prostate cancer--early experience. AB - Use of brachytherapy with radioactive seeds in the management of early prostate cancer is commonly used in the United States. The early experience has been reported from the prostate treatment centers in Seattle for the last 10 years. In this manuscript we are reporting our early experience of 150 radioactive seed implantations in early stage prostate cancer using either Iodine 125 or Palladium 103 seeds. The average age of the patient is 66 years and the median Gleason score is 5.4 with a median PSA of 6. A brief description of the evolution of the treatment of prostate cancer as well as the preparation for the seed implantation using the volume study with ultrasound of the prostate, pubic arch study using CT scan of the pelvis and the complete planning using the treatment planning computers are discussed. We also have described the current technique which is used in our experience based on the Seattle guidelines. We plan a follow-up report with the results of the studies with longer follow-up. PMID- 9973781 TI - Use of high frequency oscillatory ventilation (HFOV) for respiratory distress syndrome (RDS). PMID- 9973783 TI - Inhale deeply ... it's safe. PMID- 9973782 TI - Tax exempt hospitals' condition improves with new physician recruitment guidelines. PMID- 9973784 TI - [Association between carotid lesions evaluated by Doppler color echocardiography and cardiovascular risk factors in the elderly. Preliminary results]. AB - BACKGROUND: The valuation of the extracranial carotid by echo color-Doppler takes on an extraordinary importance for the prevention of cerebral ictus at geriatric age. In this "naturalistic" study a population of old people (> 65 yrs) of Cagliari's province was considered in order to: 1) discriminate the lesions of the carotid that are imputed to atherosclerotic disease by anatomic changes of the arterial wall caused by aging; 2) study relations between lesions of the carotid and cardiovascular risk factors. METHODS: The carotids of 50 old subjects were studied by echo color-Doppler and the lesion classified in different classes of severity, according to the hemodynamic standard, comparing them with the presence of the most important cardiovascular risk factors. Hypercholesterolemia was the most frequent risk factor (76%), followed by hypertension (62%), over weight (54%) and smoking (42%). Moreover a diffused intima-media thickening (IMT) was constant in all the subjects with values > 0.75 mm; athero-sclerotic plaques were even present in 39 subjects which only in 4 cases could be considered at risk of cerebral ischemia. RESULTS: A significant correlation between the severity of the lesions and levels of total cholesterol and LDL cholesterol for the male sex emerged, while for smoking only a trend of correlation has been obtained. CONCLUSIONS: Considering this experience it is suggested that in old subjects the presence of a diffused IMT with values > 0.75 mm must be considered as a marker of aging of the arterial wall of the carotid and not as a cardiovascular risk factor as reported in the literature for the middleaged. PMID- 9973785 TI - [Percutaneous transluminal angioplasty in the treatment of occlusion of the subclavian artery. Preliminary results]. AB - BACKGROUND AND AIMS: The authors examine the treatment of steno-occlusive diseases of the subclavian artery using transluminal percutaneous angioplasty in order to evaluate the correct indications and analyse the results. METHODS: The classic method was used according to Gruentzig's technique, following the surgical isolation of the brachial artery. All 15 patients (11 males, 4 females, mean age 64 years old) were suffering from stenosis of the subclavian ischemia during physical exercise (13), resting (2) or vertebrobasilar insufficiency. Diagnostic evaluation took the form of bilateral sphynghomanometric measurement, echo-Doppler of the cervico-brachial vessels when resting and during exercise, as well as selective arteriography in 13 cases. Intra- and postoperative arteriographic control was always performed and the method was declared successful if residual stenosis was less than 30% with a delta AP between the two lower limbs of less than 10 mmHg. Mean follow-up was 12 months. RESULTS: The immediate results included the onset of complications linked to hematoma of the arm and two small dissections of the subclavian artery which were treated conservatively. Residual stenosis, albeit not hemodynamically significant, appeared in 26.7% of patients (4 cases). One case of total occlusion without clinical symptoms and two non-hemodynamically significant re-stenoses were observed in the long term. CONCLUSIONS: The authors discuss the indications and results of this method and compare them with the data reported in the literature. PMID- 9973787 TI - [Thrombolytic therapy using r-TPA in Budd-Chiari syndrome in the course of myeloproliferative diseases]. AB - Budd-Chiari syndrome is a rather unusual clinical entity; among others, myeloproliferative disorders not infrequently are reported as a cause of this syndrome. In the past prognosis of Budd-Chiari syndrome was usually very poor. However, in recent years treatment with fibrinolytic agents has proved to be often successful in Budd-Chiari syndrome, as well as in other thrombotic disorders. In particular, r-TPA has appeared to be effective, due to its thrombospecificity. Three cases of Budd-Chiari's syndrome associated with myeloproliferative disorders are described, in which r-TPA administration, together with treatment of underlying disease, resulted in a complete recanalization of sovrahepatic veins. r-TPA, due to its thrombospecificity, has been shown to be more effective than other thrombolytic agents; its use is associated with a lower number of hemorrhagic events and it may be repeated in the case of uncompleted response. PMID- 9973786 TI - [Epidemiologic evaluation of cardiac decompensation and its impact on health costs]. AB - BACKGROUND: Heart failure is a frequent pathology that requires a high degree of hospitalization. These characteristics have a high assistance cost. The purpose of this study was to evaluate the prevalence, acuteness, predisposing factors and therapy carried out in patients of a northeastern Italian town, and to evaluate their impact on health costs. METHODS: We have examined patient under observation of the Department of Emergency at the Padua Hospital for 12 months. They had been hospitalized for heart failure symptoms. They all underwent individual and pharmacological anamnesis, objective exam, ECG, thorax X-rays and echocardiogram. The health expenses were calculated in relation to hospital stay, the cost of daily assistance, exams and medical treatments used. RESULTS: 630 patients of both sexes (422 males and 208 females) aged 74.6 +/- 6.1 were studied. Among significantly interrelated factors were: hypertension in 51.4% of the patients; diabetes mellitus in 9% of the patients; hypercholesterolemia in 31.3% of the patients; hypertriglyceridemia in 7.2% of the patients; cigarettes smoking in 19.3% of the patients, whereas obesity was present in 19.7% of all the subjects. Heart diseases directly correlated with heart failure were respectively: myocardial ischemia (65.6%); hypertensive cardiopathy (14.7%); idiopathic dilatative (15%); and valvular cardiopathy (4.7%). In 9.5% of cases, patients presented episodes of TIA, ictus, or they were carriers of neurologic focal deficiencies. As far as NYHA functional class was concerned, the third was most prevalent with a different distribution (p < 0.05) between males and females. ACE inhibitors, digitalis and calcium antagonists are to be indicated among the most widely used drugs. The health cost for patients in this survey was deduced on the basis of: average; hospitalization stay (9.8 days); estimated daily expenses for patient and for further controls (L. 282,000); the area of users (85% of residents). Therefore the full hospital assistance of patients with heart failure is approximately L. 2.1 thousand millions. CONCLUSIONS: Given the high preponderance of heart failure, the frequent relation with vascular risk factors and with ischemic cardiopathy, further investigation is necessary to curb these high rates. On the other hand, the NYHA advanced state of patients is not likely to allow lower costs in relation to hospital admission or the reduction of hospital stay. Nevertheless, the individualization of standardized therapeutic protocols and an adequate home care surveillance follow-up may reduce the number of hospitalizations and consequently the connected health expenses. PMID- 9973788 TI - A secondary aortoenteric fistula, successfully treated with proper preoperative diagnosis. AB - A rare case, presented as a secondary aortoenteric fistula after an abdominal aortic aneurysmectomy with Y-graft replacement 9 months earlier, is reported. The course was clinically very unique, in that the first manifestation of the aorto enteric fistula occurred while the patient had already been hospitalized after the orthopaedic surgical treatment for the pyogenic vertebral spondylitis. After the episode of gastrointestinal bleeding, radiological studies were promptly collected, and with the proper diagnosis, a successful surgical treatment was given under the stable hemodynamic condition, and the patient recovered uneventfully. Retrospectively considered, there are several findings that would suggest that seemingly a secondary aorto enteric fistula could have resulted from an early process of the primary aorto enteric fistula having been under progress without any detectable manifestations before the previous aneurysmectomy. The diagnostic values of computed tomography and the scintigraphy for this rare clinical entity is also underlined. PMID- 9973789 TI - [Laparoscopic adrenalectomy. A retrospective comparison with traditional methods]. AB - BACKGROUND: After 3 years from the introduction of laparoscopic adrenalectomy in an endocrine surgery unit the results are retrospectively compared with those achieved by traditional techniques with the aim of comparing the respective advantages. METHODS: During this period 68 laparoscopic adrenalectomies have been performed. The main pre-, intra- e postoperative parameters of the adrenalectomies for benign neoplasm have been examined. Mean follow-up was 51 months (65.3 for open adrenalectomy and 18.8 for laparoscopic). RESULTS: Statistical studies were homogeneous between the two groups. The laparoscopic adrenalectomy--with the same effectiveness--thanks to less peritoneum and parietal stress, is followed by fewer postoperative complications, faster resumption of biological functions, earlier return to work and better cosmetic results. CONCLUSIONS: On the basis of our personal experience laparoscopic adrenalectomy is to be considered the treatment of choice in the majority of adrenal benign neoplasms. PMID- 9973790 TI - [99mTc pertechnetate scintigraphy and premedication for the search for ectopic gastric mucosa in Meckel's diverticulum]. AB - BACKGROUND: Meckel's diverticulum (MD) is the most common anomaly of the large intestinal tract (1-3%) and is more frequent in children (62% < 2 years) and in males (66%). It often involves ectopic gastric mucosa which manifests through gastrointestinal bleeding in 50% of cases. 99m-Technetium scintigraphy (99mTcO4) is one of the procedures available for the non-invasive diagnosis of ectopic gastric mucosa. METHODS: Twenty-eight patients (11 females, 17 males), including 16 children and 12 adults, aged 8 months-80 years old, were included in the study. The patients were admitted to hospital for hematochezia and melena (22) associated with abdominal pain (5): 3 patients repeatedly presented occult blood in their stools. Two patients only suffered from abdominal cramps and one only anemia. Patients were studied using plain abdominal radiographs and ultrasound; 10 underwent gastroscopy and colonoscopy; radiological contrast studies were performed in 5 patients. All tests were inconclusive. All the patients were premedicated with oral cimetidine (20 mg/kg in pediatric patients and 300 mg q.i.d. for adults, 48 hours before the test) or with ranitidine i.v. (1 mg/kg, max 50 mg, in 20 minutes, one hour before the test); barium meals and colonoscopy were deferred for 2-3 days after examination. An intravenous injection of 37-180 Mbq of 99mTcO4 was given followed by a dynamic study of the abdomen in anterior projection. Images were acquired for one hour or until the visualisation of abnormal foci of intake: in this case, lateral and oblique images were acquired for a better localisation of the suspicious area. Some patients were administered furosemide i.v. (0.75 mg/kg). All underwent a follow-up period of 12 months. RESULTS: Pertechnetate scintigraphy was positive in 10 cases and the presence of ectopic gastric mucosa was confirmed by surgery. The study was negative in 18 cases: 3 of them were discharged with a diagnosis of Salmonella infection, polyp of the small bowel or ulcer of the large bowel respectively; the other 15 patients did not show symptoms of onset during follow-up. CONCLUSIONS: These results confirm the high diagnostic accuracy of pertechnetate scintigraphy to detect ectopic gastric mucosa if associated with H2-receptor-blocking agent premedication. PMID- 9973791 TI - [Total gastrectomy and malnutrition]. AB - BACKGROUND: The operation more frequently performed for gastric malignancy is total gastrectomy. METHODS: Our reconstructive technique is Roux en Y esophago jejunostomy, jejunal interposition after gastrectomy. In the next weeks after operation there is always an important, sometimes pathologic, slimming in gastrectomized patients. But is this slimming due to malnutrition or malabsorption? This is the real question. In our Institute a quarterly perspective clinical and instrumental follow-up for these patients has been prepared. RESULTS: We started with 41 patients, but we conducted the complete study only on 23. Of these patients, 56% have lost 10 kg weight, 25% 5 kg and 18% have not lost weight after 2 weeks from discharge dimission. But after 5 weeks, all patients had stabilized their own weight, and 18 months later the first two groups regained weight again, 1-2 kg. With our follow-up, we had educated patients to a correct personal natural diet necessary to normal social and working life. With our program in 3-4 weeks the weight of each patient was stable and we were able to control the malabsorption. CONCLUSIONS: Moreover, according to personal experience, it is important to plan a follow-up to rehabilitate patients to usual social life. This program allows to evaluate malnutrition and the possible iron or vit. B12 deficiency. PMID- 9973792 TI - Pylorus and pyloric vagus preserving gastrectomy treating 125 cases of peptic ulcer. AB - BACKGROUND: With a view to preventing the sequelae of conventional subtotal resection of stomach, such as dumping syndrome, intestinal fluid reflux and other such complications and maintaining the normal movable physiological function of the remnant stomach, we have designed a pylorus and pyloric vagus preserving gastrectomy (PPVPG). METHODS: As many as 125 cases of peptic ulcer (GU 49, DU 76) were so treated without a single death. Comparative studies were made with 48 cases of operations done at the same period with Billroth. In reducing acid, both modes of operations are identical. RESULTS: 97.9% of the Billroth cases saw more than two degrees of intestinal fluid reflux, 5.8% of the PPVPG cases had only one. Dumping syndrome occurred in the Billroth cases, none in PPVPG cases. In gastric emptying, food digestion and absorption, body weight and life quality, PPVPG proved superior to Billroth. In the subsequent follow-ups for 5.5 years, no recurrence of the disorder has been reported, curative effect proved to be Visik I or II, 98.4%. CONCLUSIONS: Safe and adaptable to a wide variety of indications, PPVPG carves not only a new course for the surgical treatment of peptic ulcer, but also can be applied to other benign gastric lesion such as polyposis, leiomyoma and ectopic pancreas. PMID- 9973793 TI - [The role of drainage and antibiotic prophylaxis in thyroid surgery]. AB - BACKGROUND: It is our habit to employ an open drainage after thyroid surgery in our department. We have also found a large number of surgical infections in these patients (5.8% vs 2.5). Aim of the study is to evaluate prospectively if contamination happens during surgical procedure or in a later time according to the presence of the open drainage. METHODS: From October 1995 to November 1996, 113 patients who underwent a subtotal thyroidectomy were randomized into two groups: group A with antibiotic prophylaxis (57 patients) and group B without it (56 patients). RESULTS: One case (1.7%) of sepsis among 57 patients of group A and 2 cases (3.4%) among 56 patients of group B were observed. CONCLUSIONS: No statistical difference was found between the two groups despite antibiotic prophylaxis covering surgical procedure. It is personal opinion that sepsis arose after surgical procedure, due to the presence of the open drainage. PMID- 9973794 TI - [The surgical physiopathology of essential pulmonary emphysema and volume reduction intervention]. AB - The breaking of the interalveolar septa represents, in the pathogenetic mechanism of emphysema, a final event, common to the different etiologic agents. This elementary injury causes a series of consequences, essentially of mechanic structural type (intrapulmonary aerial spaces-confining parenchyma collapse, bronchial obstruction, dead space augmentation) on the thin and articulate bronchoalveolar architecture, whose final rearrangement determines, at least in part, the clinical picture. In short, the break of alveolar septa involves the formation of intraparenchymal aerial spaces with collapse of the confining lung; the compensatory mechanism to this situation, involves the hyperexpansion of the thoracic cage and flattening of the diaphragm, with the aim of allowing ventilation of the healthy residual parenchyma. Because of the finite capability of expansion of the thoracic cage and of the diaphragm in respect to the theoretical capability of the lung of large intraparenchymal aerial spaces formation, it is easy to imagine that emphysema can cause a serious functional respiratory deficit even before a significant quantity of pulmonary parenchyma is destroyed by the pathogenic process. It may then be hypothesized that a simple reduction of the volume of the lung, even sacrificing a part of "working" parenchyma, might allow the residual lung to come back to a normal ventilation, wholly ameliorating the respiratory exchanges. The clinically more remarkable consequence of lung volume reduction is the amelioration of ventilation mechanics with a decreased respiratory work due to the shift of the tidal volume toward values less proximal to the maximal expandability of the thoracic wall and of the diaphragm. On the other end, it is possible to anticipate an equally significant effect on bronchial obstruction, due to the more favorable matching of the compliance of the thoracic wall and that of the lung. LVRS has significant effect on the TV sharing ratio between emphysematous spaces and residual healthy parenchyma; the hyperexpansion of the residual lung in fact causes the distension of the emphysematous spaces, continuing in the natural compensatory mechanism of the emphysema. The decreased ventilation and thus re-breathing of the residual emphysematous spaces, together with the improved ventilation may ameliorate hypercapnia. Obviously no direct effects can be expected from LVRS on the conditions of the alveolar membrane and thus on gas diffusion capacity through it. The time duration of the amelioration achieved with the lung volume reduction is still to be demonstrated. PMID- 9973795 TI - [The solitary rectal ulcer today. A review of the literature]. AB - The solitary rectal ulcer (SRU) is a benign lesion of adults of either sex, which presents with chronic constipation, peculiar defecatory disorders, rectal prolapse and smaller psychological abnormalities. The characteristic appearance of this disease is a "neither being always ulcerate, nor always solitary" lesion, but often with polypoid or granular feature, typically localized in anterior rectal wall, a few inches from anal channel. Distinctive histopathological specimens are localized mucosal distortion, hypertrophic proliferation of muscularis mucosae and obliteration of lamina propria by fibroblasts and muscle fibres from the muscularis mucosae. Very few intermittent or recurrent symptoms are rectal bleeding and mucous discharge with defecations, difficulty of a complete ampullar evacuation and sometimes pelvic or rectoperineal pain. Clinical picture and endoscopic biopsies led to diagnosis. Barium enema, defecography, transrectal ultrasound, manometry and electromyography have an additional role. Medical treatment is performed by high-fiber diet, but biofeedback training is very helpful. Surgical management is as an excisional surgery, as a rectopexy if there is prolapse. Fecal diversion and rectocolic resection are considered only for patients with obstinate and severe symptoms. Even in patients who seem to advocate a surgical approach it is important to heal a dyskinetic puborectalis muscle. PMID- 9973796 TI - [Rare anorectal malformations. Intermediate-type anal agenesis with a rectocutaneous fistula]. AB - A case of anal agenesia with recto-cutaneous fistula is presented. The recto cutaneous fistula in an intermediate or high anomaly seldom noticed so that it is not included in the common classifications. The surgical approach performed by us was that described by Mollard. The anterior perineal pull-through, under proximal protective enterostomy, allow to reduce the rate of postoperative complications and sequences and obtain--as in our patient--a normal continence and sphincteric function with an excellent esthetic outcome. PMID- 9973797 TI - [Cystic lymphangioma of the mesentery. A case of intestinal obstruction and a brief review of the literature]. AB - Mesenteric cystic lymphangioma is a rare pathology which is not often described in the literature. Moreover, its etiopathogenesis is still uncertain. It may remain asymptomatic or it may present aspecific painful abdominal symptoms of the sub-acute type correlated with compressive phenomena or, more rarely, with acute intestinal obstruction. Surgery is the only form of treatment for both acute and sub-acute abdominal forms. The authors report a case of two mesenteric cystic lymphangiomas of the ileum which led to the onset of intestinal obstruction caused by ileal volvulus in a 45-year-old man. PMID- 9973798 TI - [Posttraumatic syringomyelia. A report of an atypical case]. AB - An atypical case of post-traumatic syringomyelia is reported. Clinical presentation, electrophysiological and MR findings, as well as therapeutic efforts adopted for this case are discussed in the light of pertinent literature. PMID- 9973799 TI - [Adenocarcinoma of the duodenal bulb. A clinical case report]. AB - A rare case of adenocarcinoma of the duodenal bulb, arising from adenoma and submitted to Whipple's procedure is presented. A diagnostic delay of about 3 months, according to literature is observed. This delay is generally due to the low incidence of the illness, aspecific symptoms and frequent endoscopic and radiologic false negative, most of all in lesions of the third and fourth duodenal portions. Diagnostic tools for these duodenal tumors are endoscopy and upper gastrointestinal barium studies (UGI). CT is useful to determine preoperatively the stage of the illness and can occasionally show the primary duodenal lesion, as in this case. Surgical approach is still controversial, except in lesions of the second duodenal portion, where Whipple operation is the procedure of choice, if the tumor is resectable, of course. In the other duodenal portions some authors suggest segmental duodenal resections instead of Whipple's procedure. PMID- 9973800 TI - [The prevention of adhesions in surgery. A clinical review and experimental contribution]. AB - BACKGROUND: The well-known soft tissue healing properties in some rat models as well as the modulating fibroblasts activity of heterologous collagen led us to the hypothesis that it is possible to prevent the peritoneal adhesions in the rat by interposition of the collagen after peritoneal surgery. METHODS: In this study, the use of Type I heterologous collagen in different physical forms (1% gel, lyophilized sponge, dehydrated film) for the postoperative peritoneal adhesions prevention has been evaluated. In the second part of the experiment; the 1% gel heterologous collagen including the recombinant tissue plasminogen activator (rtPA) has been applied. RESULTS: The results of both the experiments don't show any improvement in the number and the quality of the adhesions. CONCLUSIONS: It is cannot be excluded that, increasing the rtPA concentration it is possible to obtain better results, but the great cost and its potential systemic toxicity are limiting factors for its widespread use in order to prevent peritoneal adhesions. PMID- 9973802 TI - [Evaluation of the effect of a new milk formula with added nucleotides on some gastrointestinal functions. Results of a nation-wide study of 5009 infants. Pediatric Study Group]. AB - BACKGROUND: The signs and symptoms of gastrointestinal function represent one of the most frequent reasons for pediatric consultation during the first four months of life. Few studies have evaluated these clinical conditions in relation to infant diet. The aim of this study was to evaluate the effects of a new formula enriched with nucleotides (Similac Formula Plus-Abbott) on fecal consistency, wind and regurgitation. METHODS: The study was carried out using an observational type, prospective design which involved 778 pediatricians throughout Italy. From November 1996 to June 1997, a total of 5009 healthy infants were evaluated: all were born at term, aged between newborn and 4 months old. For 2 weeks after the first examination (day 0), the parents kept a record of the number and consistency of feces, frequency of regurgitation and wind in each infant. This diary was given to the pediatrician during the second and last examination (day 14). Any confusing variables, such as intercurrent pathologies, administration of drugs or diet supplements were reported to the pediatrician and corrected during analysis. RESULTS: During the course of the 2-week observation period, infants fed with Similac FormulaPlus showed a lower incidence of formed and hard feces compared to other milk formulas (34.7% vs 44.8%, p > 0.001), and likewise a lower incidence of severe regurgitation (9.7 vs 18.1%, p > 0.001) and wind (62.7% vs 72.5%, p > 0.001). CONCLUSIONS: The results of this study show that the new milk formula enriched with nucleotides has beneficial effects on the consistency of feces, wind and regurgitation and can therefore be regarded as a step towards the benefits which only breast feeding can offer. PMID- 9973801 TI - [Protective effect of oxatomide in infantile bronchial asthma. Double-blind study vs placebo]. AB - BACKGROUND: This study has been designed to assess the protective effect of oxatomide in allergic bronchial asthma of the seasonal type in young children. METHODS: The study was carried out in a paediatric clinic; sixteen children divided into two balanced groups took oxatomide in an oral suspension at the dosage of 1 mg/kg/day, or placebo for a period of 2 months. Eight patients (7 males, 1 female), aged 22 months +/- 2.83 (mean +/- SD) took oxatomide in an oral suspension at the dosage of 1 mg/kg/day, while the other eight (3 males, 5 females; 22.13 months +/- 3.48) took placebo. Efficacy was assessed by monitoring cough, dyspnea at rest, dyspnea following exercise, wheezing, sleep disorders at baseline and after 15, 30 and 60 days of treatment, on the basis of a semiquantitative scale. All side effects were recorded. RESULTS: Persistent coughing was significantly reduced (p < 0.05) after two weeks' treatment with oxatomide. Sleep disorders and other symptoms remarkably improved. Dyspnea at rest and following exercise disappeared after 15 days' therapy, while the intensity of wheezing decreased after 30 days' active treatment. In all parameters examined, oxatomide was significantly more active than placebo at the first examination (p < 0.05 and p < 0.01). Oxatomide was well tolerated and only 2 patients complained of drowsiness which required a reduction in dosage. CONCLUSIONS: Oxatomide, at the dose of 1 mg/kg/day, obtained a good control of respiratory symptoms. PMID- 9973803 TI - [Oxatomide in the treatment of atopic dermatitis]. AB - BACKGROUND: This study evaluated the efficacy and tolerability of oxatomide in patients with atopic dermatitis, caused by alimentary allergy established by prick test and/or Rast and/or challenge test. METHODS: In the study, carried out in a paediatric clinic, 40 children (24 males, 16 females), aged between 6 months and 12 years, were randomized in two groups. Twenty children were treated with oxatomide (1 mg/kg/day) in one evening dose and the other 20 were treated at the same dosage, divided into two administrations. In the case of poor therapeutic response, 15 days after the start of treatment, it was possible to double the dosage. The skin symptoms were monitored for the efficacy. RESULTS: For all symptoms there was a significant reduction of severity within the fifteenth day (p < 0.01). Twenty eight children showed significant improvement with the disappearance of both cutaneous lesions and itching; to achieve these results in four cases (3 BID, 1 UID) it was necessary to double the dose (2 mg/kg/day). Eight children achieved a fair control of itching, with a slight improvement of eczema, while five children, despite the increase in dosage of the drug, did not get any substantial benefit. Three children were lost in follow-up, while in another case treatment was suspended because of the onset of an urticarious rash. CONCLUSIONS: The results confirm the efficacy of oxatomide in the control of itching connected with alimentary allergy independently of the posological scheme. Tolerability was excellent in both groups and no important side-effects were recorded. PMID- 9973804 TI - [Vesico-ureteral reflux in pediatrics]. AB - Vesico-ureteral reflux (VUR) is the most frequent uropathy involving 1-2% of children. Genetics, familiarity, race gender and age intervene in the pathogenesis of VUR. In particular, neonatal VUR seems to represent a specific entity. Different factors determine a renal damage due to RVU: direct action of VUR (back pression), urinary tract infection (UTI), inflammatory mechanisms and renal dysplasia. Micturing cystourethrography and nuclear cystography are currently performed for the diagnosis of VUR, being ultrasound examination aspecific. Functional parameters are now investigated in association with new morphologic studies. The strict relationship of VUR and UTI is discussed. The treatment (medical, surgical) of VUR is not well established, although some guidelines can be suggested. Finally an adequate support must be given to the family for an optimal management. PMID- 9973805 TI - [Early deterioration of the mother-child relation. "Time with families" as a model for prevention and therapy]. AB - "Time with families" is the model of service presented in this paper. Its approach is rooted in the theory of attachment by J. Bowlby. Starting from the observation of attachment patterns in mothers and children, this Service aims at promoting short-term, cost-effective and highly focused interventions enabling the child to structure secure "Internal Working Models". "Time with families" started in 1988 in the area served by the Health Welfare District 36 in Lombardia, as an integrated socio-sanitary program aimed at preventing problems in the early relations between mother and child. This program is the result of a cooperation between different services, including SIMEE, Family and Pediatric Counselling Services and Social Services. Three are the main components of the program: 1) the "First Days" program, based on health visits made by professionals to support the new mother in taking care of the newborn; 2) the clinic of child neuropsychiatry to evaluate and treat problems in the early relation between mother and child during his first three years of life through two technical approaches: short mother-child psychotherapy and functions' integrated therapy; 3) "Time with families", with a Day Center open for parents and children to ease their reciprocal relationships in this period of life, to start and realize clinical interventions and to offer individual and group counselling to parents. Thanks to this varied offer of services, its flexibility and multidisciplinarity of its approach, "Time with families" can be considered a bridge service between prevention and therapy, able to monitor and follow-up parents' and children's health conditions and to determine their styles of attachment so to intervene in at-risk situations to prevent future complications or long term consequences. PMID- 9973806 TI - [True splenic cysts. Two clinical cases]. AB - Two case reports of epidermoid cyst of the spleen are presented. Only 700 cases have been reported so far. Although splenic cysts are benign lesions and could involve spontaneously, the risk of rupture of a large cyst is high, so a diameter of 5 cm was suggested as the higher limit for nonsurgical treatment. For many years the surgical treatment of splenic epidermoid cysts was splenectomy: however recognition of the short and long-term complications of radical splenectomy had led to the practice of splenic preservation (partial splenectomy, total cystectomy, laparoscopic cyst decapsulation). PMID- 9973807 TI - Simultaneous detection of HPV and other sexually transmitted agents in chronic urethritis. AB - BACKGROUND: Many pathogens may be responsible of Non Gonococcal Urethritis (NGU) with the possible occurrence of symptomatic and asymptomatic mixed viral and bacterial infections. In particular, genital papillomaviruses (HPVs) have been searched since they are linked to both benign and malignant lesions of the penis and urethra and the presence of a potential male carried state has received limited scrutiny while the screening of sexually active females has received substantial attention. METHODS: In male patients affected by chronic NGU, the presence of DNA of Chlamydia trachomatis, herpes simplex virus (HSV) type 1 and 2 and human papillomaviruses by PCR and the occurrence of Gram positive and Gram negative micro-organisms, of Mycoplasma hominis and Ureaplasma urealyticum, by conventional cultural methods have been investigated. RESULTS: Results obtained indicated a high percentage of mixed infections, up to 36%. Genital HPV DNA was detected in 31% of specimens positive for two or more agents, and HSV DNA was detected in 10% of studied population. CONCLUSIONS: The concomitant presence of different infectious agents could determine latent, sub-clinical or chronic infections with periodic reactivation. In particular results suggest that HPV and HSV may stimulate cytokine production which can up regulate the expression of other infectious agents and may be responsible for latent chlamydial infections characterised by the persistence of this micro-organism in an altered form, viable but in a culture negative state. Therefore an increased awareness of mixed infections is relevant to define the management and treatment of chronic urethritis. PMID- 9973808 TI - Nonpalpable undescending testis. Value of magnetic resonance imaging. AB - BACKGROUND: Magnetic resonance imaging (MRI) was performed in 18 male patients with 20 nonpalpable undescended testes and the results were compared with surgical findings. METHODS: The MRI examination located 13 (65%) of 20 gonads, all found at surgery. Eleven testes were found in the inguinal canal or just proximal to the internal inguinal ring, and two testes were demonstrated above the internal inguinal ring. RESULTS: Of the seven (35%) negative results, three were false negative and four agenetic testes were not found surgically. There was no false positive result. Thus, MRI had a sensitivity of 78.6% and specificity of 100% in the demonstration of nonpalpable undescended testes. CONCLUSIONS: MRI appears to be a more reliable and noninvasive method for the localization of nonpalpable undescended testes. PMID- 9973809 TI - [Diverticula of the female urethra. Comparison of imaging techniques]. AB - BACKGROUND AND AIMS: Urethral diverticula is a rare pathology with an incidence varying between 0.3 and 6%. It is difficult to diagnose owing to the aspecificity of its clinical symptoms. The aim of this study was to evaluate the imaging techniques now available for its diagnosis. METHODS: The sample consisted of 19 female patients aged between 20 and 53 years old undergoing diverticolectomy owing to urethral diverticula between 1980 and 1996 at the 4th Division of the Department of Urology at "La Sapienza" University of Rome. All patients underwent preoperative X-ray examinations (micturitional cystourethrography and P positive urethrography). A retrospective study was performed in order to evaluate the accuracy of the individual methods. RESULTS: Micturitional urethrocystography showed a sensitivity equivalent to 77% of cases. P positive urethrography showed a 85.7% accuracy rate. Lastly, transvaginal ultrasonography, which always showed the diverticular sac in all patients in which it was used, also highlighting multiple and divided diverticuli which were not visible using traditional radiology. The latter method is easy to use and well tolerated by patients; moreover, it shows the spatial relations of the diverticulum and allows the characteristics of periurethral tissues to be evaluated. CONCLUSIONS: The authors affirm that transvaginal ultrasonography is the first method of choice for the diagnosis of urethral diverticula. PMID- 9973810 TI - Hormonal profile of patients with Leydig cell tumors: a urologic cause of gynecomastia. AB - It is possible to hypothesize an alternative role for estrogens as a predisposing factor for testicular abnormalities: estrogen exposure during development in perinatal life may initiate cellular changes which would require estrogen and/or androgen later in life for promotion to hyperplasia or neoplasia. We reviewed the literature on Leydig cell tumors and the hormonal modifications they induce. In adult patients with Leydig cell tumors, although the serum estrogen (E2) and testosterone (T) varied, the T/E2 ratio was constantly low, and the chorionic gonadotropin administration produced an higher estrogen response than in normal men. Hormonal follow-up after orchidectomy for Leydig cell tumors has not been frequently described, and both normalization and lack of normalization of T, E2, gonadotropins and hCG have been reported. In the last part of the review we analyzed the principal urologic causes of gynecomastia in men. Testicular failure, either primary or secondary is a frequently found etiology for gynecomastia. Leydig cell tumors may elevate estrogen levels, and approximately 20% of patients with these tumors have gynecomastia. PMID- 9973811 TI - Major surgery (radical cystectomy with urethrectomy) in a patient with von Willebrand's disease type I. Reliability and limits of hemocoagulative tests. AB - Patients with bleeding disorders frequently need medical or surgical care. The case is reported of a man with von Willebrand's disease type I undergoing radical cystectomy with urethrectomy for multicentric bladder cancer with neoplastic involvement of prostatic urethra, who developed serious bleeding complications which can not be predicted with conventional coagulation in laboratory. The use of the thromboelastograph (TEG) in the critical postoperative period was decisive. The tracing alterations allowed to assess the clotting disorder, constantly counterbalancing the baseline deficit and the blood loss. PMID- 9973812 TI - [Eosinophilic cystitis: an incidental diagnosis. An underdiagnosed entity]. AB - The authors report on two cases of eosinophilic cystitis diagnosed by chance, are reported. Both patients had suffered from prostatic and vesical diseases. Since the endoscopic appearance and clinical manifestation of this disease are aspecific, the diagnosis of eosinophilic cystitis is always made on histological specimen. Even if it has been described as a rare entity, personal opinion is that the real incidence of eosinophilic cystitis is underestimated. The main features of pathogenesis and therapy are also described. PMID- 9973813 TI - [Sertoli cell tumor. Case report]. AB - A case of Sertoli cell tumor is described. It represents 1% of testicular neoplasms. Its clinical features, histology, histogenesis and treatment on the basis of the current literature are reported. The malignant potential of this kind of tumor is also stressed. PMID- 9973814 TI - [Urologic complications of diverticulosis of the colon]. AB - In this paper the complications of colonic diverticulosis are reported, on the basis of two clinical cases personally observed. In the first case, a 68 year-old man, the typical symptomatology with pneumaturia, cloudy urine and watery diarrhea suggested a uro-colonic fistula, therefore a fistula between sigma and bladder, caused by a perforate diverticulum, has been diagnosed by means of cystography and barium enema. In the second case, a 64 year-old woman, the irritative symptomatology, hematuria and endoscopic picture suggested a vesical neoplasia. An accurate examination with abdominal TAC and barium enema, showed a perforate diverticulum between uterus and bladder, without affecting the bladder lumen. The surgical treatment required, in both cases, a left hemicolectomy, a minimal bladder resection in the first case, and a greater one in the second case. During the discussion, the main etiopathogenetic causes of uro-colonic fistulae together with the variants in the onset symptomatology, have been stressed. PMID- 9973815 TI - [Secondary varicocele as a clinical manifestation of primitive retroperitoneal tumor]. AB - The retroperitoneal primitive tumors are rare and the majority are malignant. Frequently the preoperative diagnosis is difficult because they show many clinical symptoms depending on the organs involved. A case of primitive retroperitoneal tumor with left varicocele syndrome as a first clinical manifestation is described. PMID- 9973816 TI - [Colposuspension with propylene mesh. A new technique for correction of urinary stress incontinence]. AB - The results of colposuspension for correcting urinary stress incontinence, both transabdominal, like Burch procedure, and transvaginal like Stamey-Pereyra procedure are, up to date, good, but not perfect at long-term. The cutting of the tissues from distal end of the sutures seems to be the main reason of failure of the operation. The authors propose a new technique of colposuspension by means of a particular suture made by the joining a prolene-mesh and a prolene-suture bilaterally placed along the urethra to obtain a strong, but natural support without risk of urethral erosion. The authors present the preliminary report of the first sixteen consecutive operations performed in patients with genuine urinary stress incontinence of first and second degree, according to Blaivas classification, diagnosed by medical history, objective findings, urodynamic tests and cystography. The follow-up in all the patients was six months: undoubtedly brief, but sufficient to refer on the feasibility and the efficacy of the procedure, the easy performing and the scarce onset of early complications as wound infection or troubles related to the prolene-mesh. PMID- 9973817 TI - Indirect immunofluorescence for of anti-jejunum antibody detection in celiac disease: comparison among different antigenic substrates. AB - BACKGROUND: Although anti-endomysium antibodies (EmA) are the most reliable serological markers of celiac disease (CD), there is a need for low-cost methods for screening programs, as clinically silent disease is increasingly recognized. AIM: To evaluate the suitability of monkey, rat and rabbit jejunum as a substrate for the determination of anti-jejunun antibodies (JAB) in CD. METHODS: JAB of IgA class were detected by indirect immunofluorescence on frozen sections of jejunum from monkeys, white rats and domestic rabbits. Sera from 61 untreated adults with biopsy-proven CD and EmA positivity in 57 out of 61 entered the study as true positives, while sera from 60 controls were considered as true negatives. RESULTS: The sections of monkey jejunum showed the characteristic pattern of elongated villous fluorescence, a ring-like positivity of the cryptal basement membrane, an endomysium-like fluorescence along the smooth muscle layers in the tunica muscolaris, while pericryptal fluorescence was not so evident on rat and rabbit jejunum. As compared to EmA positivity, the prevalence of JAB on monkey, rat and rabbit tissues was respectively 57/57, 54/57, 52/57. Two sera among 4 Ema negatives proved positive for JAB. No false positivity resulted from EmA and JAB on monkey jejunum, while a lower specificity was found for JAB on rat and rabbit substrates. CONCLUSIONS: Although monkey, rat and rabbit small intestine appeared to be a suitable alternative substrate for determination of IgA-JAB, because of its lower cost and higher availability, it cannot replace monkey oesophagus, and be recommended for wide use. PMID- 9973818 TI - Effects of gastrojejunostomy on pancreatic and gastric carcinoma, pancreatitis, gastric ulcer and other disease states of the gastro-intestinal tract. AB - BACKGROUND: To evaluate the palliative effects of gastrojejunostomy in patients who have been diagnosed with pancreatic and gastric carcinoma, and other disorders of the gastrointestinal tract. METHODS: EXPERIMENTAL DESIGN: retrospective medical records review. SETTING: Honolulu area teaching hospital. PATIENTS/PARTICIPANTS: one hundred and thirty-nine patients, 27 of whom had diagnosed pancreatic carcinoma while the remainder had other diagnoses ranging from gastric carcinoma, gastric ulcer, and cancers of nearby anatomical structures such as the ampulla of Vater, between 1985 and 1990. RESULTS: Forty eight percent (48%) of pancreatic cancer patients were female. The group consisted of 30% Japanese, 30% Caucasian, and 15% Hawaiians/part Hawaiians. Six (22%) underwent a Roux-en-Y gastrojejunostomy (GJ), thirteen (48%) obtained a loop GJ, while the remainder (30%) had a Whipple. Seven (26%) had a biliary bypass besides their GJ. No significant difference existed with regard to the failure of GJ, whether it was performed on a patient with pancreatic cancer or for any other diagnosis. Incidence of delayed gastric emptying was similar between the two groups. CONCLUSIONS: Gastrojejunostomy is effective in patients with pancreatic cancer, and meets the goal of effective gastro-intestinal function regardless of the initial diagnosis. PMID- 9973820 TI - Usefulness of echocardiography in the assessment of internal medicine inpatients. An analysis according to ACC/AHA guidelines. AB - BACKGROUND: We aimed to analyze the importance of echocardiography in our Internal Medicine Institute. We think that this technique could have a large impact in the evaluation of the internistic inpatient who is usually affected by multiple pathological problems. METHODS: Analysis was performed according to the ACC/AHA guidelines for the application of echocardiography. The data of 1211 consecutive inpatients were analyzed. RESULTS: Sixty-three per cent of all the patients had two or more associated diseases. Moreover, patients in whom echocardiography could be considered appropriate or useful were 67%. Our results point out that echocardiographic examination is generally a technique of great importance for the evaluation of internistic inpatients. CONCLUSIONS: This study could represent a useful background for a cost/benefit analysis that should evaluate the utility of a specifically-dedicated echocardiographic laboratory for optimal, autonomous management of internal medicine inpatients. PMID- 9973819 TI - Different reactivity against HCV proteins (RIBA 3) according to progression of liver damage. AB - BACKGROUND: Aim of the study was to assess the correlation between clinical stage of HCV-related liver disease and viraemia to immune response to different viral antigens. METHODS: We considered 1330 patients with HCV chronic infection followed up from 6 months up to 6 years divided into two groups according to RIBA 3 (Abbott) response: Group I, 1231 patients with positivity for at least two bands (83 subjects with asymptomatic infection, 941 with chronic hepatitis, 201 with cirrhosis and 6 with HCC); Group II, 99 patients with positivity at only one band (45 with asymptomatic infection, 53 with chronic hepatitis and 1 cirrhotic). RESULTS: We noticed a major percentage of positive patients for at least three bands in more severe clinical forms (90% of chronic hepatitis or cirrhosis versus 60% of asymptomatics, p < 0.005, chi 2 test). Moreover we noticed a percentage increase of positivity for antibodies anti-c100 and anti-NS5 with the progression of liver damage, statistically significant differences between asymptomatics and patients with chronic forms. We also observed that viraemia is related neither to clinical stage nor to different reactivity to RIBA 3, albeit viraemia is usually detected more frequently among patients with liver damage, but unrelated to different reactivities. CONCLUSIONS: Our results show a clear correlation between number of reactivities towards HCV proteins and progression of liver damage, pointing out that immune response plays a direct role in the long-term outcome of HCV infection. PMID- 9973821 TI - Effect of pulsed magnetic fields on triglyceride and cholesterol levels in plasma of rats. AB - BACKGROUND: Liver is a crucial organ in metabolism. For instance liver is the main source of circulating lipoproteins. METHODS: In this paper cholesterol and triglyceride plasma levels were measured in male rats previously exposed to pulsed magnetic fields (PMF) used in therapy. Rats underwent a one-hour exposure to a 6 mT 12 Hz PMF. RESULTS: Twenty-four hours after the end of the exposure to the PMF the rats' livers were heavier, cholesterol and triglyceride plasma levels decreased. All these variations were significantly different according to a variance ratio test as was a rebound in triglyceride level 48 hours after the end of the exposure. Normal values were observed 48 and 96 hours after the end of exposure respectively for cholesterol and triglycerides. CONCLUSIONS: These alterations may be due to a reversible accumulation of either triglycerides or of their precursors in liver following acute exposure to a 12 Hz PMF. PMID- 9973822 TI - Loss of endothelium mediated vascular relaxation as a response to various clamping pressure. Part I. A pharmacological study. AB - BACKGROUND: The contraction/relaxation response of thoracic aortal rings clamped with two clamping pressures to KCl, noradrenaline and carbachol was studied. METHODS: Clamp A had the tip pressure PA = 0.60 N/mm2 and clamp B PB = 5.16 N/mm2. In fifteen Wistar albino rats, weighing 328 +/- 19 g (mean +/- SD) the thoracic aorta was occluded for 15 minutes and then three vascular rings (2 mm wide) were excised. The proximal unclamped ring served as a control. From distal rings the diameter of the aorta was calculated from their circumference 1.61 +/- 0.01 mm (n = 15, dmin = 1.51 mm, dmax = 1.70 mm). The rings were challenged with cumulative additions of KCl (10-80 mmol/l) to measure the contraction. Then cumulative relaxation to carbachol (0.01-100 mumol/l) as a response to noradrenaline precontraction (0.1 mumol/l) was determined. RESULTS: A significant loss (p < 0.05) of vascular relaxation in all clamped rings (clamped with PA and PB clamping pressures) was seen. No significant differences (p > 0.05) were observed for contraction between clamped and control rings clamped with clamp A, however the rings clamped with clamp B showed a significant reduction in contraction (p < 0.05). No significant differences were seen from control rings between groups A and B (p > 0.05), or from clamped rings between groups A and B (p > 0.05) for both the contraction and relaxation part of experiments. CONCLUSIONS: Endothelial vascular layers are much more susceptible to pressure injuries than was previously believed. PMID- 9973823 TI - Loss of endothelium mediated vascular relaxation as a response to various clamping pressures. Part II. Direct measurements of clamping pressures and scanning electron microscope study. AB - BACKGROUND: We used novel equipment for measuring the direct tip pressure (P) of a clamp arm on the vessel wall and studied the relationship between endothelial injuries and various clamping pressures. METHODS: A strain gauge was applied to the surgical clamp arm and connected via amplifier to a 12-bit analogue-digital converter on a PC--MSDOS computer. In the on-line in vivo measurements on rat thoracic aorta a momentary peak clamping pressure (MPCP) as well as the lower stationary clamping pressure (SCP) was defined. Clamping forces of two clamps commonly used in cardiovascular microsurgery were tested in the experiment on rat thoracic aortas: clamp A had the tip pressure p = 0.60 N/mm2 and clamp B p = 5.16 N/mm2. After 15 minutes of occlusion, the thoracic aorta was excised and scanning electron microscopy studies for aortas clamped with clamp A and clamp B were performed. RESULTS: Great endothelial lacerations with complete disruption of the endothelial layer in the rings clamped with the clamp B were seen, but no disruption in rings clamped with clamp A. CONCLUSIONS: The clamping vessel wall injuries, particularly in endothelial layers, depend on the momentary peak clamping pressure as well on the lower stationary clamping pressure. PMID- 9973824 TI - Plasma levels of arginine vasopressin in hepatorenal syndrome. AB - BACKGROUND: The etiology of hepatorenal syndrome is still incompletely understood, but the non-osmotic release of arginine vasopressin (AVP) seems to have an important role in its pathogenesis. The aim of the study was to investigate the circulating plasma concentrations of AVP in patients with hepatorenal syndrome, compared with healthy controls, in relation with plasma osmolality. METHODS: Venous blood samples were drawn in 20 healthy subjects and in 20 patients with HRS for the determination of the plasma levels of AVP by radio-immunoassay and of plasma osmolality. The comparison between the two groups was carried out by the Student "t"-test for unpaired data; the plasma AVP levels were correlated with the values of plasma osmolality by linear regression analysis. RESULTS: The patients presented significantly (p < 0.001) higher plasma AVP levels in respect to controls; on the contrary, plasma osmolality was significantly lower in patients than in controls (p < 0.005). Whereas a significant (r = 0.83; p < 0.001) relationship was demonstrated between plasma AVP and osmolality in controls, no significant (r = 0.23; p > 0.05) correlation was found in patients. CONCLUSIONS: These results confirm the existence of an activation in the release of AVP in hepatorenal syndrome, due to the activation of the sympathetic adrenal system and to hyponatriemia. The contraction of diuresis in hepatorenal syndrome, on the other hand, is not due to a deficiency in plasma AVP. AVP release occurs despite low plasma osmolality, which normally inhibits its secretion. This great upset in functional organization, together with that of the atriopeptin-renin-angiotensin-aldosterone system, could play an important role in promoting and/or in the maintenance of the hydro-electrolyte imbalance that characterizes the syndrome. PMID- 9973825 TI - Early dysfunction of iris sensory fibres in diabetic patients. AB - BACKGROUND: The present study was designed to propose transcutaneous electrical nerve stimulation (TENS) of the infratrochlear nerve as a noninvasive test useful in the detection of early iris small nerve fibre dysfunction in patients with diabetes mellitus. METHODS: A total of 32 diabetic patients with no symptoms or signs of diabetic neuropathy were enrolled from a clinical practice. Sixteen of them, 6 women and 10 men, ranging in age from 19 to 53 years, had been affected by IDDM for 13 +/- 2 years. The remainder, 6 women and 10 men, age range 32 to 58 years, were suffering from NIDDM (duration of manifestation 5 +/- 1 years). Twenty-six healthy individuals, 11 women and 15 men, ranging in age from 21 to 47 years, served as controls. Pupil area changes induced by TENS of the infratrochlear nerve were investigated. The electrical stimulus was not painful and consisted of a single square wave pulse of 40 mA intensity and 0.8 ms duration. Measurements were carried out by means of a TV monocular electronic pupillometer. RESULTS: A clear-cut miosis was provoked in controls (p < 0.01 versus basal values 100 sec to 220 sec from stimulation). NIDDM patients also showed a miotic response, but it was slower in onset (p < 0.05 versus basal values 140 sec after stimulation) and shorter (p < 0.01 at 180 sec from stimulation) in duration. No pupillary changes were registered in IDDM patients. CONCLUSIONS: An abnormality of iris sensory nerve fibres in inducing pupillary constriction was detected in both diabetic groups. The differences in the severity of the dysfunction could be related to the differences in duration of the disease among the diabetic patients in the two groups. In conclusion, TENS of the infratrochlear nerve could represent an original noninvasive method in detecting early iris sensory alterations in diabetic patients. PMID- 9973826 TI - Nitrite plasma levels in type 1 and 2 diabetics with and without complications. AB - BACKGROUND: The authors thought it interesting to examine the interrelationship between nitric oxide and diabetes mellitus by the determination of the nitrite plasma levels, stable end-products of nitric oxide, in various clinical patterns of diabetes mellitus. METHODS: Our series consisted of 161 female subjects (mean age 54 +/- 7 years, disease duration 5 +/- 3 months) subdivided into: a) 13 patients suffering from insulin-dependent diabetes (IDDM) without clinical and instrumental signs of micro- and macro-angiopathy; b) 148 suffering from non insulin-dependent diabetes mellitus (NIDDM) of whom: 1) 52 without vascular complications (28 normal weight, BMI < 25, and 24 obese, BMI > 30); 2) 40 with clinical and instrumental signs of non hypertensive coronary heart disease (CHD); 3) 25 with CHD and hypertension (arterial blood pressure over 160/95 mmHg); 4) 31 with hypercholesterolemia (values over 250 mg/dl). All patients were examined in good glycometabolic conditions reached by oral hypoglycemiant (12 cases) or insulin (149 cases) treatment. As normal control 37 female subjects (mean age 48 +/- 7) without internistic diseases were considered. For each sample we determined the plasma levels of nitrites by the Gutman and Hollywood method. RESULTS: Almost similar nitrite plasma levels in IDDM (17 +/- 0.5 mumol/L) and normal controls (17 +/- 0.2 mumol/L) were found; in non complicated non obese NIDDM a not significantly elevated value (21 +/- 0.8 mumol/L) as compared with the IDDM and control group was found; the obese NIDDM patients showed a value (18 +/- 0.4 mumol/L) not significantly different in comparison with the non obese NIDDM group. In the NIDDM group with non hypertensive CHD) the nitrite values was almost similar (20 +/- 0.5 mumol/L) to the corresponding group without vascular complications. In the patients with CHD and hypertension the nitrite level was superimposable (20 +/- 0.7 mumol/L) on the one recorded in NIDDM patients without vascular complications and in those with CHD without hypertension. In NIDDM patients with hypercholesterolemia the mean nitrite value was sharply elevated (24 +/- 0.8 mumol/L); the difference between this group and those of non hypercholesterolemic, non obese, obese and CHD (with or without hypertension) patients was significant (p < 0.05). CONCLUSIONS: It is conceivable that diabetes mellitus per se causes a tendential not significant increase of NO production in comparison with normal controls; some factors such as blood pressure, overweight, disease duration, therapeutic treatment and coronary complications appear not to influence NO production. In hypercholesterolemic diabetic patients the nitrite enhanced level in plasma might mean a compensatory response to a continuous inactivation of NO involved in a protective competition towards damaging factors and chiefly against oxidised LDL. PMID- 9973827 TI - Ruptured abdominal aortic aneurysms: factors affecting the early postoperative outcome. AB - BACKGROUND: In spite of the progress in diagnosis and treatment of ruptured abdominal aortic aneurysms (RAAA) the mortality rate still remains very high (varying from 15% to 50% according to various experiences). This study is aimed at analyzing the relative contribution of preoperative hemodynamic conditions and of operative and postoperative factors to outcome of patients operated on for ruptured abdominal aortic aneurysms. METHODS: For this purpose a retrospective case series involving 152 patients operated on in emergency for RAAA, during the period 1990-1994, has been reviewed. In this group we examined the site of rupture, the size of the aneurysms, the presence or not of a shock condition at admission, the existence of inflammatory aspects, the adopted type of prosthesis. RESULTS: The mortality rate was 24.3% (37 patients). In 10 patients (27%) the cause of death was an irreversible hemorrhagic shock. Eight patients (21.6%) died for an intestinal infarction. In 7 patients the fatal outcome was due to the development of an acute renal failure. Five patients (13.5%) underwent an acute myocardial infarction and other five a multiorgan failure. Two patients (5.5%) eventually died for respiratory insufficiency. CONCLUSIONS: The results of our study seem to confirm that the outcome of patients affected by rupture of abdominal aortic aneurysms depends not only on the preoperative hemodynamic condition but also on the expertise of the surgical team. PMID- 9973828 TI - Effect of T-activin therapy on indomethacin modulation of lymphoproliferative response in vitro of melanoma patients. AB - BACKGROUND: Several studies showed that PGE-mediated immunosuppression in cancer patients may be differentially affected by conventional oncologic therapy. METHODS: Since there is little evidence about the action of immunotherapy on this suppression mechanism, we investigated the effect of therapy with a thymic agent T-activin, on in vitro modulation of lymphoproliferative response (LPR) by indomethacin. RESULTS: The results demonstrated that indomethacin added in vitro enhanced LPR in early stage melanoma patients before therapy. T-activin therapy as an adjunct to surgery improved this lymphocyte function; the post-therapy in vitro addition of indomethacin did not significantly affect mitogen response. However, in those patients whose LPR was insufficiently enhanced by immunotherapy (3/8), indomethacin had improved their lymphocyte response. In the control patient group treated by surgery alone, indomethacin significantly enhanced LPR in vitro six months after operation. Although obtained in a small number of patients, our results indicate that the enhancing effect of T-activin therapy on lymphoproliferative response may be, at least in part, due to the effect on PGE mediated suppressor cell activity. CONCLUSIONS: Furthermore, post-therapy in vitro testing may indicate a possible usefulness of this drug combination in some of the early stage melanoma patients. PMID- 9973830 TI - Branched graft technique for middle aortic syndrome. Three case reports. AB - BACKGROUND: Middle aortic syndrome is a rare disease caused by stenosis of the distal thoracic and abdominal aorta involving the visceral and renal arteries. METHODS: We performed reconstructive bypass surgery for three middle aortic syndrome patients. We used magnetic resonance angiography as well as conventional angiography to assess the stenotic vessels. According to these data, branched graft was fabricated preoperatively. We selected Dacron for aortic bypass graft, and ePTFE for the branch graft. In previous reports, branched graft was not applied for the surgery for middle aortic syndrome. RESULTS: Using this branched graft, the clamping time and ischemic time of the organs were shortened. CONCLUSIONS: Using branched graft prefabricated according to accurate preoperative angiographic findings, the reconstructive surgery is thought to proceed more safely. PMID- 9973829 TI - Systemic lupus erythematosus and pregnancy. AB - In this paper the authors underline the importance of SLE in women, above all those who become pregnant. This review also stresses the importance of an early diagnosis and the need to give correct information to pregnant women regarding the possible risks of pregnancy, both to the maternal organism and to the fetus. The authors also describe the main aspects of diagnosis and the management of this particular type of patient. In conclusion, they affirm that pregnancy should not be avoided categorically, but that it should be carefully planned and, once started, must be scrupulously monitored in view of the deterioration of SLE caused by pregnancy. PMID- 9973831 TI - Undiagnosed phaeochromocytoma following infrainguinal bypass surgery. AB - We present a rare case of undiagnosed phaeochromocytoma following infrainguinal bypass surgery. The patient, a 59-year-old lady, had a one year history of hypertension following a first femoro-tibial bypass and presented as a cardiorespiratory emergency in the admission room following her contralateral femoro-tibial bypass. The patient recovered after some days in intensive care despite a delayed diagnosis. PMID- 9973832 TI - Surgical repair of ventricular septal defect associated with absence of right superior vena cava and persistent left superior vena cava: a case report. AB - A nine-month-old boy, weighing 4840 g, with VSD associated with absent right superior vena cava and persistent left superior vena cava, successfully underwent surgical repair of VSD. This anomaly is rare and causes some surgical and electrophysiological problems. We discussed these problems and described the details of surgery in our case. PMID- 9973833 TI - Unusual development of an abdominal neoplasm in a patient with Maffucci's syndrome. AB - A case of Maffucci's syndrome complicated by a mixed abdominal tumor with ascites in a 23-year-old female patient is described. As far as we know, this is the first such case in the literature. PMID- 9973834 TI - Laparoscopic cholecystectomy in a patient with mitochondrial myopathy. AB - The authors report a 27-year-old woman with mitochondrial myopathy and respiratory failure requiring nasal-CPAP administration who successfully underwent laparoscopic cholecystectomy for chronic cholecystitis. The hypothesis that minimally invasive surgery results in less operative stress is truly substantiated by the experience with laparoscopy in such patients with high risk of perioperative and postoperative complications. PMID- 9973835 TI - Mefloquine-induced grand mal seizure in tubercular meningitis. AB - Mefloquine represents a promising antimalarial drug against Plasmodium falciparum. It has been related to an increase in seizure frequency in epileptic patients and should not be administered to patients with a history of convulsions, epilepsy in first degree relatives, or serious psychiatric disorders. We report a case of a man from the Ivory Coast complaining of fever, headache and anemia treated with chloroquine and subsequently with mefloquine in the suspicion of malaria, even in the absence of laboratory confirmation. When the patient came to our division, malaria was excluded, but the patient developed two convulsive episodes, respectively 4 and 7 days after the ingestion of the second therapeutic dose of mefloquine. Further investigation was performed; particularly an EEG showed abnormalities compatible with tendency for seizures, diffuse waves and spikes. CSF culture was positive for M. tuberculosis as well as urine, sputum and blood cultures. Anti-HIV antibodies were positive, so the final diagnosis was tuberculosis in HIV infection. As seizures are common signs of cerebral tuberculomas, but not of meningitis it is possible that tubercular meningitis might have enhanced severe neuropsychiatric side effects of mefloquine. Physicians should be aware that treatment with mefloquine with concomitant meningitis could have a risk of development of grand mal seizure. PMID- 9973836 TI - Silent myocardial ischemia induced by hypoglycemia. AB - Hypoglycemia is known to produce various EKG changes, including arrhythmias. Although these changes have been rarely documented, their presence may pose diagnostic and therapeutic problems in an emergency situation. We report the case of a 81-year-old man with insulin-dependent diabetes mellitus who showed electrocardiographic features of acute myocardial ischemia during an episode of hypoglycemia; these alterations disappeared after glucose administration. PMID- 9973837 TI - Extracorporeal techniques during graft replacement of suprarenal abdominal aortic dissections. PMID- 9973838 TI - Pharmacokinetics and biodistribution of genetically-engineered antibodies. AB - Monoclonal antibodies (MAbs), because of their inherent specificity, are ideal targeting agents. They can be used to deliver radionuclides, toxins or cytotoxic drugs to a specific tissue or malignant cell populations. Intact immunoglobulin (IgG) molecules have several practical limitations of their pharmacology; their relatively large size of approximately 150,000 daltons leads to a slow clearance from the blood pool and the body resulting in significant exposure to normal organs with limited quantities delivered to tumors. The IgG molecule shows a relatively poor diffusion from the vasculature into and through the tumor. Attempts to modify the pharmacology of the Ig molecule have classically involved the use of proteases to generate F(ab')2 and Fab' fragments with molecular weights of approximately 100,000 and 50,000 daltons, respectively. Fv fragments of IgG are one of the smallest size functional modules of antibodies that retain high affinity binding of an antigen. Their smaller size, approximately 25,000 daltons, enables better tumor penetration and makes them potentially more useful than a whole antibody molecule for clinical applications. Molecular cloning and expression of the variable region genes of IgG has greatly facilitated the generation of engineered antibodies. A single-chain Fv (scFv) recombinant protein, prepared by connecting genes encoding for heavy-chain and light-chain variable regions at the DNA level by an appropriate oligonucleotide linker, clears from the blood at much faster rate than intact IgG. The scFv fragment can retain an antigen-binding affinity similar to that of a monovalent Fab' fragment; this however, represents a relative decrease in binding affinity when compared to intact antibodies. The scFv with its faster clearance and lower affinity results in a lower percent-injected dose localizing in tumors when compared to the divalent IgG molecule. This may be adequate for imaging but probably not for therapy. The valency of the MAb fragment is critical for the functional affinity of an antibody to a cell surface or a polymeric antigen. In attempts to generate multivalent forms of scFv molecules, non-covalently linked scFv dimeric and trimeric molecules, disulfide linked dimeric scFvs, as well as covalently linked chimeric scFvs have been studied. These multivalent scFvs generally have a higher functional affinity than the monovalent form resulting in better in vivo targeting. Another way to alter the pharmacology of the scFvs is to modify its net charge. Charge-modified scFvs with desired isoelectric points (pI), have been prepared by inserting negatively charged amino acids on the template of the variable region genes. This can help to overcome undesirable elevations in renal uptake seen with most antibody fragments. In conclusion, genetic manipulations of the immunoglobulin molecules are effective means of altering stability, functional affinity, pharmacokinetics, and biodistribution of the antibodies required for the generation of the "magic bullet". PMID- 9973839 TI - Improving monoclonal antibody pharmacokinetics via chemical modification. AB - The aim of radioimmunotherapy in treating solid tumors is to target tumor sites while sparing normal tissues. This can best be achieved by using a monoclonal antibody (MAb) with high tumor uptake and rapid clearance. Because MAbs are basic, positively charged proteins, and mammalian cells are negatively charged, the electrostatic interactions between the two can create higher levels of background binding resulting in low tumor to normal organ ratios. To overcome this effect, investigators have attempted to improve MAb clearance by using various methods such as secondary agents as well as chemical and charge modifications of the MAb itself. The use of a second agent to remove the MAb involves using a biotinylated MAb followed by treatments with a molecule like avidin. Charge modification can be accomplished by conjugating a chemical moiety with a positive, negative or neutral charge to residues exposed on the surface of MAbs. Experimental results demonstrate that the lowering of the isoelectric point by this method correlates with a decreased clearance time and improved tumor targeting. Altering the pharmacokinetic characteristics of intact MAbs with charge modification can improve their clearance times to rates similar to those of MAb fragments. Several groups have reported on the effects of chemical modification using molecules such as dextran, PEG, lactose and biotin. Some of these modified MAbs retain the antigen binding specificity of the parent molecule and have improved clearance characteristics from blood and other organs. Hence, these methods can be used to improve both the diagnostic and therapeutic potential of MAbs by improving the signal to noise ratio and the absolute tumor accretion of MAb, respectively. PMID- 9973840 TI - Effects of linker chemistry on the pharmacokinetics of radioimmunoconjugates. AB - Radiolabeled monoclonal antibodies reactive with tumor-associated antigens can selectively deliver cytotoxic or diagnostic isotopes to malignant cells in vivo. To achieve maximum retention of radiolabel in tumor and a more rapid clearance of radioisotope from normal tissues, six linker immunoconjugates were evaluated in studies using nude mice and beagle dogs. All radioimmunoconjugates contained a mouse monoclonal IgG (QCI) reactive with human ferritin. Different chemical linkages were inserted between immunoglobulins and the radiolabeled chelate (DTPA). Three linkers (ITCB, DSS and BSOCOES) were stable in in vitro and in vivo studies. Three linkers (EGS, DST and DSP) were labile in in vitro and in vivo studies. Indium-111 labeled antiferritin-containing ITCB or DSS linker showed high uptake in human hepatoma xenografts in nude mice. In addition, long blood half-lives and higher normal liver uptakes were noted. Studies of whole body retention of radioimmunoconjugates showed approximately three-fold faster elimination of radioimmunoconjugates containing a labile linker (EGS). EGS linker is the labile linker with the highest therapeutic ratio: higher tumor uptake, but low normal liver uptake and a shortened blood half-life of the radioimmunoconjugate. The differences in normal tissue uptake (liver) between EGS and ITCB were confirmed in beagle dogs. Urine elimination studies and incubation or radioimmunoconjugates in serum or tissue homogenates of tumor, liver or muscle, showed that enzymes in serum and liver homogenates were able to cleave the labile linkers, which led to a more rapid elimination of low molecular weight radioactive metabolites in urine. The metabolism of linker radioimmunoconjugates in tumor was less effective. The labile linker DSP appears less useful because sulphydryl groups that are generated by cleavage of cause higher uptake radioactivity in normal kidney. Biodistribution studies in nude mice were confirmed by serial immunoscintigraphy studies on individual mice. The immunoscintigraphy studies are semi-quantitative only, but enable the use of lower numbers of experimental animals. This is of particular significance in large experimental animals such as beagle dogs. The labile linker approach can reduce normal tissue radiation exposure. The study also provides an example of preclinical optimization of radioimmunoconjugates. Continued use of the appropriate preclinical animal models will accelerate more successful applications of radioimmunoconjugates in cancer patients. PMID- 9973841 TI - Strategies to reduce renal radioactivity levels of antibody fragments. AB - Antibody fragments such as Fab and single-chain Fv fragments possess many advantages over intact antibodies as vehicles to deliver radioactivity for diagnostic and therapeutic applications. However, radiolabled antibody fragments exhibited high and persistent localization of the radioactivity in the kidney, which compromises diagnostic accuracy and therapeutic effectiveness. Recent studies indicated that the persistent localization of renal radioactivity would be originated from the re-absorption of glomerularly-filtered radiolabeled antibody fragments, followed by the retention of the radiometabolites generated after degradation in the lysosomal compartment of the renal cells. Two major approaches have been performed to reduce the renal radioactivity levels of antibody fragments. One is to block the reabsorption of radiolabeled antibody fragments themselves at the proximal tubular cells from the luminal fluid by administration of basic amino acids such as L-lysine. The other approach is to decrease the residence time of the radiometabolites within the lysosomal compartments of the renal cells by introducing a cleavable linkage between antibody fragments and radiometabolites of rapid urinary excretion. Another approach to reduce renal radioactivity levels of antibody fragments may be to release radiolabeled compound of urinary excretion from glomerularly-filtered antibody fragments before they are reabsorbed into the renal cells by the action of brush border enzymes present on the lumen of the renal proximal cells. In this paper, recent studies of the three approaches to reduce the renal radioactivity levels of antibody fragments are briefly reviewed. PMID- 9973842 TI - Liposomes for scintigraphic imaging: optimization of in vivo behavior. AB - Liposomes, microscopic lipid vesicles consisting of concentric phospholipid bilayers enclosing discrete aqueous spaces, have been investigated extensively as carries for drugs in attempts to achieve selective deposition and/or reduced toxicity. Liposomes radiolabeled with gamma emitters (67Ga, 111In and 99mTc) have been used for imaging purposes. Liposomes as formulated in the past, are rapidly taken up by cells of the mononuclear phagocyte system, primarily those located in liver and spleen. However, it has been shown during the last two decades that the in vivo behavior of liposomes can be modulated by modifying their formulation. The size and the lipid composition have a major influence on the blood clearance rate, hepatic uptake and splenic uptake of liposomes. The development of long circulating liposomes, in particular coating of the bilayer with polyethyleneglycol (PEG) resulted in liposomes that oppose recognition by the MPS, thus displaying even longer circulatory half-lives. By carefully adjusting the liposomal formulation, the in vivo characteristics of liposomes can be tailored such that they become suitable vehicles for imaging various pathological processes in vivo. Liposomes have been proposed for tumor imaging, for infection imaging and as blood pool markers. Here, the factors that determine the in vivo behavior of liposomes and the current status of liposome-based radiopharmaceuticals are reviewed. PMID- 9973843 TI - The influence of stereoisomerism on the pharmacokinetics of Tc radiopharmaceuticals. AB - The influence of stereoisomerism on the pharmacokinetics of Tc mono-oxo complexes is reviewed. Tc(V) monooxo complexes formed with N/S ligands have four donor groups from the ligands in an equatorial plane; the oxo ligand coordinates in an axial position. Stereoisomerism in Tc (V) mono-oxo complexes can be centered within the ligand (carbon atom in the chelate ring or ligating nitrogen of amine donors) or at the Tc. The metal center becomes chiral when an equatorial ligand has a head and a tail (i.e., the two ends of the ligand differ). All types of stereocenters can produce significantly different pharmacokinetic profiles for individual isomers. Thus, biological evaluation of separated stereoisomers is necessary to identify the optimal sterochemical configuration, particularly for radiopharmaceuticals targeted to receptor molecules with low specificity. Because of interspecies variation, there is ultimately no substitute for human testing. Although it is possible that the increase in non-specific binding of agents incorporating L-vs D-amino acids may more than offset any increased receptor binding, much more information is needed. Stereochemical factors can also lead to unpredictable differences in coordination geometry and thermodynamic preference of a single isomer; thus chemical characterization of stereoisomers continues to be an important component of radiopharmaceutical development. PMID- 9973844 TI - [Tobacco and chronic inflammatory bowel disease]. PMID- 9973845 TI - Relationship between smoking and colonic involvement in inflammatory bowel disease. AB - The effects of smoking on the onset and clinical course of inflammatory bowel disease (IBD) have been widely debated. Although smoking appears to have a clearly unfavorable effect on the course in Crohn's Disease (CD), the relationship between smoking and localization of the disease is less clear. AIM: To evaluate, in our group of patients, the relationship between smoking and the development of ulcerative colitis (UC) or CD, and between smoking and the localization of CD in the large bowel or in other sites. PATIENTS AND METHODS: The smoking habits of 171 patients at the time of diagnosis were assessed with a questionnaire. Subjects were classified into three subgroups as smokers, nonsmokers and ex-smokers. Current smokers were grouped according to their level of consumption as those who smoked fewer than or more than 10 cigarettes per day. A total of 161 patients were studied (UC n = 69, CD n = 92). Patients with CD were divided into those with colonic disease and those with no colonic involvement. We evaluated the relationship between smoking and the form of IBD, localization (colonic or noncolonic) and the presence of perianal disease (PAD) in CD. The results were analyzed with the chi-squared test. RESULTS: Smoking was more frequent in patients with CD than in those with UC (72.8% vs 31.9%). Among patients with CD, more patients without colonic involvement were smokers (84.6% vs 64.2%). However, among patients with CD involving the colon, smoking was significantly more common (64.2%) than among patients who had UC (31.9%). CONCLUSIONS: Our findings confirm a relationship between smoking and CD. Smoking seems to be associated with some degree of protection of the colonic mucosa, especially in heavy smokers. PMID- 9973846 TI - Epidemiology and prevalence of seropositivity for hepatitis C virus in pregnant women in Granada. AB - OBJECTIVES: To study personal and familial antecedents of risk and prevalence of infection by HCV in pregnant women in the south area of Granada. PATIENTS AND METHODS: We included in the study 3003 pregnant women of the south area of Granada during the period from January 1993 to December 1995. Anti-HCV was detected in the third trimester of pregnancy by second and third generation ELISA, and positive results were confirmed by RIBA 3. We also determined HCV-RNA and genotype. Finally, we analyzed ALT levels in 1171 (39%) pregnant women. We carried out an epidemiological survey of all pregnant women, which included the following personal antecedents: transfusion, intravenous drug use, liver diseases, risk profession and sexually transmitted diseases. We studied the same antecedents in the parents, husbands and other relatives. RESULTS: Prevalence of anti-HCV was 0.63% (19 cases) with ELISA and 0.53% with RIBA. HCV-RNA was positive in 14 (74%) genotype 1b (57%) being the most frequent. ALT was increased in 52 (4.4%) pregnant women, 7 (13.5%) of whom were anti-HCV positive, versus 12 women (1%) in the normal ALT group (p < 0.001). In the epidemiological study we observed statistically significant differences in: a) housing characteristics [2125 (71%) anti-HCV negative pregnant women living in occupant-owned housing versus 7 (36%) in anti-HCV-positive group, p < 0.001]; b) personal antecedents of transfusion, chronic or acute hepatitis, or intravenous drug use (p < 0.001) (these factors were confirmed in the multivariable analysis), and c) familial antecedents of the husband (p < 0.05). CONCLUSIONS: In this study we demonstrated that 0.53% of the pregnant women were infected by HCV; most of them were HCV-RNA positive and was genotype 1b was the most frequent. The risk factors most frequently associated with infection were antecedents of transfusion, intravenous drug use and acute or chronic hepatitis. PMID- 9973847 TI - Computerized tomographic assessment of the composition of gallstones. AB - We present the results of an in vitro study of biliary lithiasis (n = 106) with computerized tomography (CT). We analyzed the correlation between composition of gallstones (crystallographic analysis of thin sections and atomic absorption spectrophotometric analysis of total calcium content) with CT patterns (densitometry) and their corresponding attenuations. Six main CT patterns were distinguished: hypodense (homogeneous and heterogeneous), dense, homogeneous hyperdense, ringed hyperdense and irregular hyperdense. Statistically significant differences (p < 0.05) were found between attenuations for cholesterol (mixed and pure) and pigmentary stones. We found a good inverse correlation between attenuations and cholesterol content; the contents of pigment, inorganic calcic salts and total calcium content also showed significant direct correlations (p < or = 0.01). Of the samples classified as pure cholesterol type stones, 86.4% showed hypodense patterns, and the remaining 13.6% showed irregular hyperdense patterns. Of the pigmentary stones, 80% showed homogeneous hyperdense images. All stones that contained more than 3% calcium produced hyperdense patterns, whereas 72.4% of the stones that contained less calcium produced hypodense images. Tomodensitometric measurements provided more information than simple radiography, and made it possible to distinguish a greater variety of gallstone types based on structural complexity. PMID- 9973848 TI - Current management of colonic volvulus. Results of a treatment protocol. AB - Colonic volvulus affects mainly the geriatric population and is associated with a high number of complications when treated by emergency surgery. The development of alternative methods has replaced and reduced the number of traditional surgical procedures. We present the results of treatment of colonic volvulus in a surgical service in Alicante, Spain. Between 1993 and 1997 a total of 17 cases in 15 patients were diagnosed, 16 in the sigmoid colon and 1 in the cecum. In 9 (60%) patients endoscopic devolvulation was successful. In 2 (22%) of these patients the problem recurred, and was resolved by a second endoscopic treatment. Three patients (20%) required surgery, and 3 others (20%) were treated with radiological reduction (barium enema) and rectal catheter. The average hospital stay of patients treated with endoscopy and barium enema was 2-3 days, being 7 days in patients who underwent surgery. Management with endoscopy is initially effective in most cases of volvulus of the sigmoid colon. This procedure affords decompression and adequate preparation of selected patients for surgical resection, which is the treatment of choice and provides the greatest guarantee against subsequent recurrence. PMID- 9973849 TI - [Nitric oxide and inflammatory bowel disease]. AB - Nitric oxide (NO) is an important biological mediator with effects on homeostasis, neurotransmission and immune function. Chronic inflammation of the intestinal mucosa in patients in ulcerative colitis and Crohn's disease has been reported to be associated with enhanced production of NO and nitric oxide synthase (NOS) activity. Whereas small amounts of NO produced by endothelial constitutive calcium-dependent NOS may act to preserve intestinal mucosa integrity, large amounts of NO synthesised by inducible calcium-independent NOS may play a key role in further aggravation of the inflammation and may be associated with the development of intestinal mucosal injury and amplification of immune response in patients with inflammatory bowel disease (IBD). In this article we review NO pathways, mechanisms of action, functions, regulation, immunogenetics and the role played in IBD. A deeper knowledge of the NO physiopathology may allow new therapeutical approaches in IBD patients. In fact, the development of selective inhibitors of NOS isoforms could provide a novel therapeutic option in the management of IBD patients. PMID- 9973850 TI - [Respiratory insufficiency resulting in death in a patient with abdominal pain, generalized adenopathies and enlarged pancreas: case record]. PMID- 9973851 TI - [Symptomatic gallstones in 80 year-old patients: surgery is the treatment of choice]. PMID- 9973852 TI - [Commentary about a new type of horizontal laparoscopic gastroplasty]. PMID- 9973853 TI - [Hypothyroidism presenting as intestinal pseudo-obstruction]. PMID- 9973854 TI - [Carcinoid tumor presenting as intestinal necrosis]. PMID- 9973855 TI - [Resolution of a case of gastric outlet obstruction after eradication of Helicobacter pylori]. PMID- 9973856 TI - Thrombolysis in the management of acute myocardial infarction. Current status and future perspectives. AB - The optimal thrombolytic regimen is front-loaded alteplase with vigorous heparinization: the reperfusion treatment that leads to the lowest 30 day mortality. The role of heparin alone or in combination with thrombolysis is still unclear. Hirudin does not provide benefit over heparin, as we have seen in the trials, and glycoprotein blockers are promising in PTCA. They can also be effective in unstable angina and possibly in acute myocardial infarction. PMID- 9973857 TI - [The surgical treatment of acute myocardial infarct in the 90s]. AB - At present, the treatment for acute myocardial infarction is revascularization during the critical initial period of six hours after the beginning of coronary occlusion. Despite the fact that surgery performed within this time period presents a hospital of mortality around 2%, and with excellent results in the long term, it is seldom used due to logistic limitations and capabilities of hospital infrastructures, high costs and the possibility of the surgical team initiating surgery inside the useful time period. Surgery is thus limited to the patients with suitable anatomy, who are not candidates or had failure of thrombolytic/angioplasty therapy and are in the six-hour period after initiation of symptoms. Surgery performed at a later stage has good results if performed in a non emergency situation, specially after the first 72 hours. Surgery continues to be the only treatment for the mechanical complications of infarction, and good results have recently been shown in ventricular septal ruptures, with hospital mortality of 14%, due to the use of an endoventricular patch in patients operated early, before the consequences of low cardiac output develop at systemic level. In the surgical treatment of mitral regurgitation, the tendency has been to use repair techniques whenever possible, but still with hospital mortality up to 15%. The recent advances of the techniques and tactics of myocardial preservation during surgery have made a very significant contribution to the better results we see today. PMID- 9973858 TI - New trends in echocardiographic evaluation of patients after myocardial infarction. PMID- 9973859 TI - Philosophy of antiarrhythmic approaches to ventricular tachyarrhythmias close to the 21st century. AB - The scientific basis and the reasoning underlying the changes in antiarrhythmic approaches to ventricular arrhythmias during recent decades are discussed. The early enthusiasm in the use of antiarrhythmic drugs in patients after myocardial infarction to prevent sudden cardiac death was severely affected by the results of the Cardiac Arrhythmia Suppression Trial (CAST) which show an increased mortality of patients on sodium-channel antagonist antiarrhythmic drugs. A transient euphoria for drugs that prolong repolarization received criticism after premature termination of the Survival With Oral D-sotalol-trial (SWORD). Recently, attention has focused on the use of the implantable cardioverter defibrillator in both secondary and primary prevention of sudden death. In contrast, catheter ablation, although very useful in supraventricular tachycardia, still plays a limited role in the management of ventricular tachyarrhythmias in the presence of organic heart disease. PMID- 9973860 TI - Antiplatelet drugs in secondary prevention after acute myocardial infarction. AB - Clopidogrel, a new ADP receptor antagonist, selectively and irreversibly inhibits ADP-induced platelet activation and aggregation thereby preventing atherothrombosis. Clopidogrel 75 mg o.d. and aspirin 325 mg o.d. were compared in the CAPRIE trial, a prospective international multicenter double-blind trial conducted in 19,185 high- risk patients with symptomatic atherosclerotic disease. Qualifying events for inclusion into the trial were ischemic stroke (IS) within the past six months, myocardial infarction (MI) within the past 35 days or peripheral arterial disease. Duration of treatment was one to three years. The primary efficacy end point was a composite cluster of IS, MI of vascular death. Overall, clopidogrel provided an 8.7% relative risk reduction (p = 0.043) in the occurrence of a first event of the cluster over and above aspirin and a favorable trend on each of the components of the primary end point. The greatest relative risk reduction was noted for prevention of MI (19.2%). In terms of number of events prevented per 1,000 patients and per year, clopidogrel is expected to prevent 24 major atherothrombotic events versus 19 with aspirin. Clopidogrel shows a favorable safety profile with fewer cases of gastrointestinal bleeding and better gastric tolerability. PMID- 9973861 TI - [Adjuvant therapy with a glycoprotein IIb-IIa inhibitor (abciximab) in coronary angioplasties with a high thrombotic risk]. AB - INTRODUCTION: We retrospectively studied our experience with adjunctive therapy with glycoprotein IIb-IIIa inhibitor (abciximab) on patients with a high risk of thrombotic complications during coronary angioplasty (PTCA). PATIENTS AND METHODS: From September 1996 to November 1997, we performed PTCA in 210 patients, and abciximab was given to 38 (18%) of them. The interventions were urgent (primary PTCA in acute myocardial infarction) in 55% of the cases. The mean age of patients was 68.6 +/- 12 years and 71% were male. The reasons for coronary intervention were: acute myocardial infarction in 21 patients (55.3%), unstable angina in 9 (23.7%) and stable angina in 8 (21%). Coronary stents were implanted in 13 patients (34%) and an intra aortic balloon pump was used in 4 (11%). The reasons for using abciximab were: thrombus containing lesion: 22 (57.9%); other type B2/C lesion characteristics: 6 (15.9%); acute closure post balloon PTCA: 9 (23.7%), sub-acute stent thrombosis: 1 (2.6%). Oral acetilsalicilic acid and intravenous heparin were given to all patients at the beginning of the intervention. The mean APTT was 124 +/- 32 seconds at the end of the procedure. RESULTS: The arterial sheaths (8 French) were removed six hours after procedure, according to the normalisation of APTT values. Angiographic success in this group of patients was 100%. One patient died during hospitalisation due to left ventricular failure. There was no need for repeated angioplasty or coronary bypass grafting during hospital stay. The main complications related to the use of abciximab were: bleeding (requiring transfusion) in four patients 10.5%); severe thrombocytopenia (< 50,000 platelets/mm3): 1 (2.6%): cardiac tamponade (requiring pericardiocentesis): 1 (2.6%) and pseudo-aneurysm of femoral artery (requiring vascular surgery): 1 (2.6%). CONCLUSIONS: The use of abciximab as adjunctive therapy in this small group of patients undergoing coronary interventions with high risk of thrombotic complications is associated with high procedural success, but at the expense of high rates of bleeding complications. Therefore, special care must be applied during and after the procedure to enhance the safety of the patients treated with this drug. PMID- 9973862 TI - [An increase in renal dopamine production after the administration of radiographic contrast agents]. AB - Renal vasoconstriction and anti-natriuresis conditioned by radiographic contrast agents (CA) may be antagonised by the administration of exogenous dopamine. However, the influence of CA on the activity of renal synthesis of dopamine has not been studied. This study assessed the daily urinary excretion of dopamine, its precursor. L-3, 4-dihydroxyphenylaline (L-DOPA), and its metabolites (acid 3, 4-dihydroxyphenylacetic, DOPAC; homovanillic acid, HVA) 24 hours before and 48 hours following administration of a non ionic and hyposmolar (lopromide) CA in patients (n = 10; average age 61.3 +/- 4.3 years) submitted to coronary angiography. Urinary excretion of noradrenalin, a marker of sympathetic activity, was also assessed during the same period. The deputation of creatinine (Ccr) and the urinary excretion of sodium (UNa+) lowered after the administration of the CA (Ccr, 79.2 +/- 10.2 vs 72.2 +/- 9.6 ml/min/1.73 m2, p < 0.05; UNa+, 112.8 +/- 9.6 vs 61.7 +/- 25.1 mmol/24 h, p < 0.05). On the contrary, the urinary excretion of potassium increased in the period of 24 h following the administration of the AC (31.7 +/- 5.2 vs 103.8 +/- 10.8 mmol/24 h, p < 0.05). There was an increase in the urinary excretion of dopamine as well as noradrelalin during the 24 hour period following the administration of the CA (dopamine, 1260.2 +/- 196.8 vs 1571.5 +/- 170.2 mmol/24 h p < 0.5; noradrenalin, 186 +/- 36.6 mmol/24 h, p < 0.05). On the contrary, the urinary excretion of L-DOPA lowered after the administration of the CA (115.4 +/- 25.5 vs 80.5 +/- 13.2 mmol/24 h, p < 0.05). These results conditioned an increase in the dopamine/L-DOPA ratio in the urine, after the administration of the CA (12.2 +/- 1.5 vs 22.2 +/- 4.5 mmol/24 h, p < 0.05). In conclusion, the administration of CA is accompanied by an increase in the renal production of dopamine which, in these conditions, may act as a compensatory natriuretic hormone. PMID- 9973863 TI - [Therapeutic exhaustion in patients with an implantable cardioverter defibrillator. Are there predisposing factors?]. AB - In patients (pts) with implantable cardioverter-defibrillators (ICD), antitachycardia pacing (ATP) schemes may be used followed by a limited number of endocavitary shocks in the same episode of ventricular tachycardia (VT) with the potential risk of therapeutic exhaustion. OBJECTIVE: To assess the incidence of episodes of therapeutic exhaustion in a population of ICD carriers with ATP programmes and to attempt to determine their correlation with clinical variables. METHODS: Study of the episodes of VT treated by ICD in 8 patients (6 male; 2 female) with an average age of 56 +/- 17 years with a follow-up > 6 months. The underlying pathology was: ischemic heart disease-5 patients; arrhythmogenic dysplasia of the right ventricle-1 patient; hypertrophic cardiomyopathy-1 patient; and operated pulmonary valve stenosis-1 patient. The authors considered therapeutic exhaustion to be the occurrence of episodes in which VT persisted after the application of ATP and the maximum number of shocks. The patients with episodes of therapeutic exhaustion (group A-3 patients) were compared with the remaining patients (group B-5 patients) with regard to the following parameters: age; ejection fraction; previous myocardial infarction (pMI; cardiac frequency during VT (cfVT); number of episodes of non-maintained VT (NMVT) without therapeutic intervention; > 20% reduction of the VT cycle after ATP (VTATP); intensity of programmable shocks (Icho); and medication with anti-arrhythmia drugs (AA). RESULTS: In a total of 262 VT records (duration > 2.5 sec. after detection) with treatment by ICD during an average follow-up of 11 months, 6 episodes (2.3%) of therapeutic exhaustion were detected in 3 patients. Four of the episodes occurred in the same patient in a period of 4 hours, hospitalisation being necessary following syncope. In the other two cases, there were complaints of dizziness which subsided spontaneously a short time after the application of the last shock by the ICD. [table: see text] CONCLUSION: Therapeutic exhaustion occurred in about 2% of the VT treated with this population. The possibility of a high number of non maintained VT episodes being associated to a greater possibility of therapeutic exhaustion may have implications on ICD programming. PMID- 9973864 TI - [Streptococcus bovis endocarditis and colonic involvement]. AB - McNeal and Blevins published the first report of Streptococcus bovis infective endocarditis in 1945. In 1951, McCoy suggested, for the first time, that an association could exist between Group D Streptococcus infective endocarditis and colon carcinoma; this association would be demonstrated later (1977) by Klein and unquestionably confirmed by several posterior works. Due to a clinical case of Streptococcus bovis infective endocarditis, which we had the opportunity of diagnosing, a review is made of the existent literature about the association between infection by this agent and the presence of lesions in the colon. Some recommendations are made in what respects the diagnosis and evaluation of patients with Streptococcus bovis infective endocarditis. Finally, the implications and therapeutic strategies in these patients are discussed. PMID- 9973866 TI - Recommendations of a Task Force of the the European Society of Cardiology and the European Resuscitation Council. PMID- 9973867 TI - "High-load" polyethylene glycol-polystyrene (PEG-PS) graft supports for solid phase synthesis. AB - The choice of a polymeric support is a key factor for the success of solid-phase methods for syntheses of organic compounds and biomolecules such as peptides and oligonucleotides. Classical Merrifield solid-phase peptide synthesis (SPPS), performed on low cross-linked hydrophobic polystyrene (PS) beads, sometimes suffers from sequence-dependent coupling difficulties. The concept of incorporating polyethylene glycol (PEG) into supports for solid-phase synthesis represents a successful approach to alleviating such problems. Previous reports from our laboratories have shown the advantages of "low-load" PEG-PS (0.15-0.25 mmol/g) for SPPS. Herein, we demonstrate that the beneficial aspects of the PEG PS concept can be extended with resins that have higher loadings (0.3-0.5 mmol/g). PMID- 9973868 TI - The use of polyacrylamide-based peptide synthesis resins for the generation of antipeptide antibodies. AB - Antibodies directed against specific amino acid sequences can serve as probes for the protein molecules from which the sequence was derived, as well as affinity purification reagents. One of the major uses of synthetic peptides is for the production of such antibodies. Typically, antigens for this purpose are prepared by coupling the peptide to a macromolecular carrier such as bovine serum albumin or keyhole limpet hemocyanin. The steps for this process are peptide synthesis, peptide purification or desalting, coupling to the carrier protein, and purifying the peptide-protein conjugate. Techniques have emerged in which the amino acid sequence of interest is synthesized on a solid support using a noncleavable linkage and the resulting peptidyl-resin is injected into animals to elicit the antipeptide immune response. These procedures reduce the number of steps required to prepare the peptidyl-antigen. Water-compatible resins based on polyacrylamide have been utilized for this purpose. In this paper the composition of these supports and their use in the generation of antipeptide antibodies is reviewed. PMID- 9973869 TI - The psychophysical approach to manual materials handling task design. AB - For approximately three decades, researchers have utilized psychophysics to develop guidelines (weights, forces and frequencies) for manual materials handling tasks. Early work by Stover Snook and his colleagues provided the foundations of the experimental methodologies that would be used by other researchers as well as design data that would be used by practitioners. Currently, there are extensive psychophysical data for designing a variety of materials handling tasks. The current state of psychophysical data will be examined, and the psychophysical approach will be compared to the biomechanical and physiological approaches to setting limits for materials handling tasks. The advantages and disadvantages of the psychophysical approach will be discussed, as will the research needs required to address the current limitations of the psychophysical approach. PMID- 9973870 TI - Maximum acceptable forces of dynamic pushing: comparison of two techniques. AB - The purpose of this experiment was to investigate maximum acceptable initial and sustained forces while performing a push of 7.6 m, performed at a frequency of 1 push min-1 on a magnetic particle brake treadmill and a high-inertia push-cart. Eight male industrial workers performed a 40 min treadmill pushing task in the context of a larger experiment and two, 2 h push-cart tasks with a unique water loading system. A psychophysical methodology was employed, whereby the subjects were asked to select a workload they could sustain for 8 h without straining themselves or without becoming unusually tired, weakened, overheated or out of breath. The results revealed that maximum acceptable initial and sustained forces of pushing on the high inertia cart were significantly higher (28 and 23%, respectively) than pushing forces on the magnetic particle brake treadmill. It was concluded that adjustments to the pushing and pulling data bank by Snook and Ciriello (1991) may be appropriate if verification of this experiment yields similar results. PMID- 9973871 TI - Beyond psychophysics: the need for a cognitive engineering approach to setting limits in manual lifting tasks. AB - The classical psychophysical approach to setting limits in manual lifting tasks is discussed in view of experimental procedures used, non-linearity of human perception of load heaviness, and the related experimental outcomes. The results of two studies investigating the human assessment of load acceptability and safety are presented. The first study compares the classical concept of the maximum acceptable weight of lift (MAWL) to the alternative concept of the maximum safe weight of lift (MSWL). The second study utilizes the linguistic magnitude estimation (LME) method to mathematically model human assessment of four categories of lifted loads, including the concepts of acceptable, safe, not too-heavy, and too-heavy loads for continuous lifting. It is shown that the concepts of the lifted load acceptability and safety are non-linear, and can be modelled with great accuracy using the third degree polynomials. This study also introduces and investigates the concept of the load indifference in assessment of load heaviness, and shows that lack of a cognitive benchmark introduces inconsistency in subjects' perception of load acceptability and safety compared to the concept of too-heavy load for continuous lifting. It is concluded that a new research approach to manual lifting tasks based on cognitive engineering is needed to improve the quality of research methodologies currently utilized in this field. This unexplored area of research should lead to greater understanding of human capacities and limitations in manual lifting tasks in the context of cultural and linguistic anthropology. PMID- 9973872 TI - Comparison of the sensitivity of three psychophysical techniques to three manual materials handling task variables. AB - The primary objective of the study was to determine the absolute and relative sensitivity of three psychophysical techniques of physical stress determination (Borg's Scale, the Visual Analogue Scale, and the Body Part Discomfort Rating) in varied manual materials handling tasks. Ten young male and ten young female university students lifted a 22 kg box onto a shelf 132 cm high. The industrial size box (40 x 20 x 20 cm) had two cut-out handles on the top middle of the two side panels. The shelf had restricted access allowing 5 and 10 mm clearance for access. The palletizing was performed in sagittal and 45 degrees asymmetrical postures under unlimited, 90% and 80% of stature headroom. The subjects lifted the box six times per minute for 5 min. After every lift the load was automatically delivered to the starting position. The 12 experimental conditions were randomized. Following each 5-min palletizing task the subjects were required to assess the immediately foregoing task on Borg's scale, the Visual Analogue scale, and a Body Part Discomfort Rating scale. All data were subjected to statistical analysis including multivariate analysis of variance and Scheffe post hoc multiple range test. Borg's scale was able to discriminate between two clearances, two symmetries and the three headrooms (p < 0.001). The Visual Analogue scale was able to differentiate between two symmetries and three headrooms (p < 0.01), but the Body Part Discomfort Rating could not differentiate between any task conditions. Based on the study it is suggested that an appropriate match between the task demands and the basis of a psychophysical tool is essential for valid and reliable information. PMID- 9973873 TI - Assessment of human muscle strength for engineering purposes: a review of the basics. AB - Contracting skeletal muscles pull on body segments to withstand or overcome internal and external opposing forces. Various methods and techniques can be employed for measuring muscular exertions. Information on strength that can be applied to objects such as hand tools or handling loads is of great importance for ergonomic design. This paper establishes a systematic context regarding: (1) the contractile muscle actions and their associated metabolic and circulatory processes, which are often the limiting factors for exertion; (2) the internal biomechanical effects of muscle contraction in terms of the application of muscle force to body links and the internal transmission of the generated torque through the body to the point of external exertion; (3) the various kinds of muscular efforts, ranging from strictly bounded statics (isometrics) to freely executed dynamics; and (4) the ensuing possibilities to measure human muscular capabilities for the application of this information to ergonomic design of tasks and equipment. PMID- 9973874 TI - Low-back stresses when learning to use a materials handling device. AB - This study examines the potential effect of short-term practice on low-back stresses during manual lifting and lowering of a 15 kg load, and while using two different types of materials handling devices (MHDs) to lift and lower a 40 kg load. The two MHDs used were an articulated balance arm and a pneumatic hoist. The expectation was that low-back dynamic moments, EMG measured torso muscle antagonism, and EMG predicted L4/L5 disc compression forces would rapidly decrease with practice, and that the manual lift-lower activities would be learned faster than the MHD-assisted exertions. Four naive male college age subjects performed 40 lift and lower exertions, both manually and with the two MHDs for a total of 24 experiments. Non-linear regressions of the peak and average low-back moments, EMGs and disc compression values revealed only small decreases in the values (from 2 to 14%) over the 40 trials, and it was only statistically significant for five of the 48 regressions. This would seem to indicate that if learning is present in these tasks it is going to be very slow learning, and thus future studies will need to include a much larger number of trials. The effects of MHDs on the learning rates when compared to manual lifting learning rates was not statistically significant. It was shown, however, that MHDs had a particularly beneficial effect on reducing L4/L5 compression forces during load lowering activities despite the MHD load being much heavier than the manual load. It also was found that the level of torso muscle co-contraction increased significantly (2-4 times) when MHD handling was involved compared to manual lifting and lowering. PMID- 9973875 TI - The effects of lifting speed on the peak external forward bending, lateral bending, and twisting spine moments. AB - Lifting tasks that involve twisting have been repeatedly implicated as contributing to the onset of occupational back injuries in epidemiological studies. The objective of this work was to quantify the three directional external moments acting on the spine during a sagittally symmetric and two asymmetric lifting tasks. A total of 15 subjects participated in the three lifting tasks. All tasks were performed at two qualitatively defined lifting speeds, 'slow' and 'fast', and with two load magnitudes: 10 and 20% of the subject's body weight. The mid-sagittal plane lifts were performed using two horizontal reach distances: 40 and 60 cm. A four-camera, two-forceplate motion and force measurement system were used to obtain the kinematic and kinetic data as the lifts were performed. A dynamic link-segment biomechanical model was used to quantify the reaction forces and moments at the ankle, knee, and hip and L5/S1 joints. Results from all tasks showed increased sagittal plane (forward bending) spine moments with the heavier load and at the faster lifting speed (p < 0.001). Spine lateral bending and twisting moments increased during the mid-sagittal plane lifts with the greater reach distance and the faster lifting speed, respectively. The twisting moments on the spine were greatest as subjects lifted from in front and placed the load to the side but were dependent upon the lifting speed and the load magnitude. The lateral bending moments increased during this same task with the heavier load. However, the spine lateral bending moments were greatest when lifting from one side to the other. PMID- 9973876 TI - Determination of the effect of lift characteristics on dynamic performance profiles during manual materials handling tasks. AB - In any quantitative gait or occupational biomechanics investigation, the quantification of the different kinematic, kinetic, and electromyographic parameters is essential towards assessment of functional capacity and development of a biomechanical profile of the task demands. In the current study, the authors presented a methodology for using inferential statistics to evaluate the effect of lift characteristics on phase-dependent and phase-independent variability in performance. Using a database of kinematic and kinetic profiles obtained from a manual lifting study, the phase-dependent effects of lift characteristics: box mass (load), mode (technique of lift), and speed (frequency of lift) were investigated through the use of analysis of variance (ANOVA) techniques, which recognize the vectorial constitution of the profiles. In addition, the Karhunen Loeve Expansion (KLE) feature extraction method was used for representing the lifting patterns of measured joint angular position, velocity, acceleration, and net muscular torque profiles obtained from a 2-D biomechanical lifting model in order to study the phase-independent effects. In comparison to traditional descriptive statistical analyses currently used in various occupational biomechanics experimental investigations, this method allows the significant information content of the time varying signal to be captured, enhancing the sensitivity of subsequent hypothesis testing procedures. The application of this technique to MMH investigations allows identification of the lift characteristics that dominate the variability of task demands, hence aiding in the design and assessment of ergonomic solutions. PMID- 9973877 TI - Muscle responses to simulated torque reactions of hand-held power tools. AB - The aim of this work was to investigate physiological responses to torque reaction forces produced by hand-held power tools used to tighten threaded fasteners. Such tools are used repetitively by workers in many industries and are often associated with upper limb musculoskeletal complaints. The tools considered for stimulation in this study had straight handles and required from 100 to 400 ms to tighten fasteners to a peak torque of 1.0 to 2.5 Nm and from 50 to 150 ms for the torque to decay to zero. A tool stimulator was constructed to apply a programmed torque profile to a handle similar to that of a straight in-line power screwdriver. Wrist flexor and extensor surface EMGs and handle position were recorded as subjects held handles subjected to controlled torque loads that tended to flex the wrist. It was found that: (1) very high EMG values occurred even though torques were of short duration (50 to 600 ms) and the peak torques were low (7-28% of maximum strength); (2) high EMGs in anticipation of torque are directly related to torque build-up rate and peak torque; (3) high peak flexor and extensor EMGs during and following torque onset are related to torque build up rate and peak torque; (4) minimum time of peak EMGs of 72-87 ms following the onset of torques with 50 ms build-up suggests the contribution of an extensor muscle stretch reflex component; delayed peak for longer build-ups suggests a central control of muscle force in response to torque; (5) angular excursions of handles increase with decreasing torque build-up time and increasing torque magnitude causes increasing eccentric work; (6) the results show that the slow torque build-up times (450 ms) correspond to minimum peak EMGs; and (7) accumulated EMGs increase with increasing torque and torque build-up times. Further studies are needed to evaluate fatigue and musculoskeletal injuries associated with prolonged periods of tool use. PMID- 9973878 TI - Computer key switch force-displacement characteristics and short-term effects on localized fatigue. AB - This study investigates the effects of key switch design parameters on short-term localized muscle fatigue in the forearm and hand. An experimental apparatus was utilized for simulating and controlling key switch make force and travel using leaf spring mechanisms, and provided direct measurement of applied key strike force using strain gauge load cells. Repetitive key tapping was performed as fast as possible using the dominant index finger for 500 s per condition (8.3 min) and a work-rest schedule consisting of 15 s of key tapping alternating with 10 s of rest. One combination of two make force levels (0.31 and 0.71 N) and two over travel distances (0.5 and 4.5 mm) was presented randomly on four different days. Nine subjects participated. Localized muscle fatigue in the hand and forearm was assessed subjectively using a 10 cm visual analogue scale, and objectively using surface electromyography (EMG). Average peak key strike force exerted was 0.35 N less for the smaller make force and 0.59 N less for the longer over travel distance. Fatigue occurred in all cases but no significant differences were observed between key switch parameters based on RMS EMG. Subjective reports of localized fatigue after 500 s were less when the key switch make force was less; however, a corresponding over travel effect was not observed despite the greatly reduced key strike force for the longer over travel distance. This discrepancy may be explained by the greater finger movement that was observed with increased over travel. Although there was no apparent improvement in short-term discomfort from fatigue when over travel was increased, this study did not consider the potential long-term health benefits from reduced key strike force. PMID- 9973879 TI - Under-reporting of work-related disorders in the workplace: a case study and review of the literature. AB - Accurate reporting of work-related conditions is necessary to monitor workplace health and safety, and to identify the interventions that are most needed. Reporting systems may be designed primarily for external agencies (OSHA or workers' compensation) or for the employer's own use. Under-reporting of workplace injuries and illnesses is common due to a variety of causes and influences. Based on previous reports, the authors were especially interested in the role of safety incentive programmes on under-reporting. Safety incentive programmes typically reward supervisors and employees for reducing workplace injury rates, and thus may unintentionally inhibit proper reporting. The authors describe a case study of several industrial facilities in order to illustrate the extent of under-reporting and the reasons for its occurrence. A questionnaire and interview survey was administered to 110 workers performing similar tasks and several managers, health, and safety personnel at each of three industrial facilities. Although less than 5% of workers had officially reported a work related injury or illness during the past year, over 85% experienced work-related symptoms, 50% had persistent work-related problems, and 30% reported either lost time from work or work restrictions because of their ailment. Workers described several reasons for not reporting their injuries, including fear of reprisal, a belief that pain was an ordinary consequence of work activity or ageing, lack of management responsiveness after prior reports, and a desire not to lose their usual job. Interviews with management representatives revealed administrative and other barriers to reporting, stemming from their desire to attain a goal of no reported injuries, and misconceptions about requirements for recordability. The corporate and facility safety incentives appeared to have an indirect, but significant negative influence on the proper reporting of workplace injuries by workers. A variety of influences may contribute to under-reporting; because of under-reporting, worker surveys and symptom reports may provide more valuable and timely information on risks than recordable injury logs. Safety incentive programmes should be carefully designed to ensure that they provide a stimulus for safety-related changes, and to discourage under-reporting. A case-control study of similar establishments, or data before and after instituting safety incentives, would be required to more clearly establish the role of these programmes in under-reporting. PMID- 9973880 TI - Analysis of workers' compensation claims associated with manual materials handling. AB - Workers' compensation claims associated with manual materials handling (MMH) represent the single largest source of claims and costs. Surprisingly, there have been few analyses of such losses associated with MMH. An examination of the nature of the injuries associated with MMH as well as the body parts most frequently affected can lead to a better understanding of the losses attributed to MMH to suggest further research efforts. A large sample of MMH claims was analysed and stratified with respect to body part affected and the nature of the injury. The outcome measures examined were frequency (number of claims) and severity (cost measures) of the claims. The analyses revealed that the lower back area and upper extremities were the body parts associated with approximately 70% of the claims. Strain was the nature of injury most frequently reported (51.3%). Lower back area strains were the most frequently reported nature of injury and body part combination. Additionally, an analysis of median claims costs revealed the occurrence of a small number of very expensive traumatic injuries. PMID- 9973881 TI - The effectiveness of commonly used lifting assessment methods to identify industrial jobs associated with elevated risk of low-back disorders. AB - Low-back disorders (LBD) continue to be the most costly and common musculoskeletal problem facing society today. Investigators have developed tools or measures that are intended to identify jobs that will probably be associated with an elevated risk of low-back disorders. However, an important and not widely discussed issue associated with these tools and procedures has been that of the validity or effectiveness of the tools. Therefore the objective of this study was to evaluate the validity and effectiveness of two commonly used types of LBD assessment methods in terms of their ability to correctly associate jobs with LBD risk. The 1981 NIOSH Work Practices Guide for Manual Lifting and the 1991 NIOSH revised lifting equation, along with psychophysical measures were assessed for their ability to correctly identify high-, medium-, and low-risk (of LBD) jobs. Risk was defined according to a database of 353 industrial jobs representing over 21 million person-hours of exposure. The results indicated that both NIOSH measures were predictive and resulted in odds ratios between 3.1 and 4.6. Higher odds ratios were found when the maximum horizontal distance was used to assess a job compared to the average horizontal distance. Further analyses indicated that the two NIOSH assessment methods classified risk in very different ways. The 1981 NIOSH Guide demonstrated good specificity (91%) in that it identified low-risk jobs well but it also displayed low sensitivity by only correctly identifying 10% of the high-risk jobs. The 1993 NIOSH revised lifting equation, on the other hand, had better sensitivity. It correctly identified 73% of the high-risk jobs but did not identify low- and medium-risk jobs well. Using psychophysical criteria it was observed that 60% of the high-risk jobs would be judged to be acceptable, whereas, 64% and 91% of the medium- and low-risk jobs, respectively, would be judged to be acceptable. This study indicates that the different measures have various strengths and weaknesses. When controlling for occupational LBD it should be recognized that a variety of measures exist and that the measure that most appropriately assesses risk depends upon the characteristics of the job. PMID- 9973882 TI - Analysis of multiple activity manual materials handling tasks using A Guide to Manual Materials Handling. AB - Manual handling of materials continues to be a hazardous activity, leading to a very significant number of severe overexertion injuries. Designing jobs that are within the physical capabilities of workers is one approach ergonomists have adopted to redress this problem. As a result, several job design procedures have been developed over the years. However, these procedures are limited to designing or evaluating only pure lifting jobs or only the lifting aspect of a materials handling job. This paper describes a general procedure that may be used to design or analyse materials handling jobs that involve several different kinds of activities (e.g. lifting, lowering, carrying, pushing, etc). The job design/analysis procedure utilizes an elemental approach (breaking the job into elements) and relies on databases provided in A Guide to Manual Materials Handling to compute associated risk factors. The use of the procedure is demonstrated with the help of two case studies. PMID- 9973883 TI - Do workplace interventions prevent low-back disorders? If so, why?: a methodologic commentary. AB - The demand for workplace interventions to prevent low-back disorders has increased in recent years. At the same time, a crisis in the literature has become apparent: there are conflicting reports on whether or not these interventions work. With the aim of understanding the reason for the dissension in the literature, six studies were selected for close examination. These were studies of interventions based on differing principles, i.e. a change in organizational ethos to promote back safety, back belt use, the introduction of ergonomic devices, and back-strengthening exercises. If the studies are taken at face value, any of the interventions, regardless of type, has a tremendous effect. Methodological problems inherent in these studies may provide a clue to why essentially different interventions were found to be consistently successful. Study design quality has long been noted to exert a particular influence on the evaluation of outcomes: the quality of the study design is often inversely related to reported outcomes. Of the six studies selected for examination, four did not include a contemporaneous control group, five did not randomly assign subjects to test and control groups, and none included a placebo group. Given these research designs, variables other than those tested by the studies may have produced the reported results. These variables include 'beliefs of the intervention providers' and 'coalescence of the work group', both of which are discussed. Two approaches, the pragmatic and the explanatory, may be used to study workplace interventions to prevent low-back disorders. Most of the examined studies are pragmatically oriented. Having dealt with study design problems expeditiously, these studies may be characterized as more immediately responsive to the demand to evaluate workplace interventions than explanatory studies. On the other hand, explanatory studies, most notably associated with randomized clinical trials in medicine, are more rigorous. Enough pragmatically oriented studies have been conducted to suggest that workplace interventions may have an effect on low-back disorders. More conclusive explanatory studies may now be conducted. PMID- 9973884 TI - Osteoporosis in men. PMID- 9973885 TI - Longevity: the ultimate gender gap. PMID- 9973886 TI - Pills and potency: blood pressure drugs and sexual dysfunction. PMID- 9973887 TI - I know that transplanted organs have helped many patients, but I've never heard of transplanting testicles. Is any research being done in this area? PMID- 9973888 TI - Abdominal fat. PMID- 9973889 TI - New guides to herbal remedies. PMID- 9973890 TI - Hearing loss. PMID- 9973891 TI - Medicine and the media. PMID- 9973892 TI - New migraine drugs. PMID- 9973893 TI - Hot flashes and PMS. PMID- 9973894 TI - I just read about a recent report, which concluded that high consumption of milk was associated with an increased risk of osteoporosis. This flies in the face of everything I've heard about calcium. Is it really true? PMID- 9973895 TI - I have rheumatoid arthritis and have been taking methotrexate. I'm interested in the new drugs that have been in the news lately. Just how effective are they? PMID- 9973896 TI - Cardiac MR imaging. PMID- 9973897 TI - Morphological abnormalities revealed after successful intra-arterial thrombolysis of infra-inguinal native arteries and bypasses. AB - PURPOSE: To characterise morphological abnormalities depicted after successful intra-arterial thrombolysis; to determine whether these differed in infra inguinal native arteries and bypasses; and to evaluate whether balloon angioplasty was an appropriate treatment of stenoses in the acute phase after thrombolysis. MATERIAL AND METHODS: Patient records, radiology records, and angiograms from 47 patients with acute or subacute occlusions of infra-inguinal arteries (n = 21) or bypasses (n = 26) successfully treated with continuous intra arterial infusion of streptokinase, urokinase or tissue plasminogen activator were retrospectively reviewed. RESULTS: Angiographic morphological abnormalities were depicted in 18 of 21 arteries (86%) and in 23 of 26 bypasses (88%), the most common abnormality being stenoses. Haemodynamically significant stenoses were found in 15 arteries (71%) and 18 bypasses (69%). The majority of the stenoses were successfully treated with balloon angioplasty, both in native arteries (12/15; 80%) and in bypasses (14/18; 78%). CONCLUSION: Morphological abnormalities are most often shown after successful intra-arterial thrombolysis in arteries, autogenous and non-autogenous bypasses. In all types of conduits, stenoses are the most commonly revealed lesion, which in the majority of cases can be treated with balloon angioplasty. Short-term outcome after catheter directed thrombolysis and angioplasty seems fair. PMID- 9973898 TI - Central assessment of bilateral phlebograms in a major multicentre thromboprophylactic trial. Reasons for inadequate results. AB - PURPOSE: To determine the cause of inadequate bilateral phlebograms at central assessment. A major antithrombotic trial was evaluated to identify and apply corrective measures for reducing inadequate results in future multicentre trials. MATERIAL AND METHODS: The inadequate results in 253 out of 1,827 patients having undergone bilateral phlebography following total hip replacement were reviewed by two central assessors using strict criteria for evaluability. The reasons for inadequate findings were assessed and ranked. RESULTS AND CONCLUSION: Insufficient contrast filling, especially of the anterior tibial, common femoral and iliac veins, was the most common reason for disqualifying examinations. Unilateral examinations and obscuring metallic devices were the second and third most common reasons, respectively. Efforts should be made to standardize the phlebography technique, to use a large volume of contrast without tourniquets, and to obtain an appropriate number of views to visualize the deep veins. PMID- 9973899 TI - Respiratory monitoring during MR imaging. The clinical value of a new fibre optical monitor. AB - PURPOSE: To assess the clinical utility of a fibre-optical monitor for respiratory monitoring in patients undergoing MR imaging without general anaesthesia. MATERIAL AND METHODS: One hundred consecutive patients were included at each of 3 MR units (300 patients in total). The technicians estimated the value of monitoring the respiratory rate on a 5-graded scale. Conditions that might complicate the MR examination were noted. RESULTS: The respiratory monitor was well tolerated by 99% of the patients. It was rated as valuable or very valuable in one-third of the total group, but in slightly more than two-thirds of the group of patients with some condition that might have complicated the MR examination. The estimated value of respiratory rate monitoring did not correlate to the age or sex of the patients, the type of examination, or to whether contrast medium was used or not, but it was significantly more often considered valuable in patients placed in the head-first position than in those placed in feet-first. CONCLUSION: Respiratory rate monitoring during MR imaging seems to be valuable in many patients, particularly if some condition that might complicate the MR examination is present. PMID- 9973900 TI - Thymus size in preterm infants evaluated by ultrasound. A preliminary report. AB - PURPOSE: To sonographically evaluate the thymic size in preterm infants. MATERIAL AND METHODS: In 6 healthy infants, born in gestational weeks 34-37, and 6 infants born in weeks 24-32, the thymic volume estimate (the thymic index) was assessed. The measurements were compared to the estimates calculated from the prediction model for neonates. RESULTS: The slightly preterm infants fit the prediction model. In cases where the results failed to fit into the model, it was adjusted in order to cover lower birth rates. The extremely preterm infants initially had a very low thymic index but, when healthy, they reached the normal range. CONCLUSION: With the knowledge of the birth weight it is now possible to predict the thymic size in healthy infants weighing 2,070 g or more. PMID- 9973901 TI - Thymus size in infants from birth until 24 months of age evaluated by ultrasound. A longitudinal prediction model for the thymic index. AB - PURPOSE: To do a follow-up sonography assessment of the thymic size in infants at an age of 24 months, and to create a longitudinal prediction model for the thymic index covering all ages from birth to 24 months. MATERIAL AND METHODS: Of 37 infants examined in an earlier investigation, 34 attended a 24-month follow-up examination. The thymic index, a volume estimate, was assessed by sonography and compared to clinical variables, breast-feeding status and illness. The longitudinal prediction model was based on data throughout 2 years. RESULTS: There was no significant relation between the thymic index and the clinical variables, breast-feeding status or illness at 24 months. An overall test for the effect of breast-feeding status at 4 months for infants from 0-24 months was significant, as was the actual body length of the infants from 0-8 months. Prediction models were estimated. CONCLUSION: Based on a 24-month longitudinal sonography study, prediction models are presented whereby the thymic size, as an index, can be predicted at all times from birth to 24 months of age. PMID- 9973902 TI - Differentiating benign and malignant breast lesions with T2*-weighted first pass perfusion imaging. AB - PURPOSE: Invasive breast carcinomas and fibroadenomas are often difficult to differentiate in dynamic contrast-enhanced T1-weighted MR imaging of the breast, because both tumors can enhance strongly after contrast injection. The purpose of this study was to evaluate whether the addition of T2*-weighted first pass perfusion imaging can increase the differentiation of malignant from benign lesions. MATERIAL AND METHODS: Nine patients with invasive carcinomas and 10 patients with contrast enhancing fibroadenomas were examined by a dynamic contrast-enhanced T1-weighted 3D sequence immediately followed by a single slice T2*-weighted first pass perfusion sequence positioned in the contrast-enhancing lesion. RESULTS: The carcinomas and the fibroadenomas were impossible to differentiate based on the contrast enhancement characteristics in the T1 weighted sequence. The signal loss in the T2*-weighted perfusion sequence was significantly stronger in the carcinomas than in the fibroadenomas (p = 0.0004). CONCLUSION: Addition of a T2*-weighted first pass perfusion sequence with a high temporal resolution can probably increase the differentiation of fibroadenomas from invasive carcinomas in contrast-enhanced MR imaging of the breast. PMID- 9973903 TI - Plain radiography of the lumbosacral spine. An audit of referrals from general practitioners. AB - PURPOSE: To evaluate how referrals from Norwegian general practitioners for plain radiography of the lumbosacral spine conform to clinical recommendations, and whether non-conforming referrals yield important findings. MATERIAL AND METHODS: The clinical information reported in referral letters of 323 patients was compared with recommendations given in a Norwegian and in a British "guide". Additional clinical data were obtained by interviewing 100 of the patients. Using all available information, a new comparison was performed. Radiological findings were obtained from the routine reports. RESULTS: Of the 323 referrals, 24% (37%) conformed to the Norwegian (British) "guide", 34% (46%) did not conform, and 42% (18%) were considered uncertain, mainly because of lack of pertinent information in the referral letters. A total of 182 examinations were in disagreement with one or both "guides". Only 4 of these examinations revealed potentially important findings (osteoporotic fractures in 2 patients, uncertain sacroiliac joint arthritis in 1 patient, and "probably benign" sclerotic densities in 1 patient). In the interview group, the proportion of non-conforming referrals was 40% (48%) based on the referral letters, and 31% (30%) when the interview data were taken into account. CONCLUSION: A great proportion of referrals for plain radiography of the lumbosacral spine do not conform to recent clinical recommendations. Referrals outside the advised criteria yield few relevant findings and could probably be cancelled. They require at least supplementary information to justify radiography. PMID- 9973904 TI - MR evaluation of the articular cartilage of the femoral head during traction. Correlation with resected femoral head. AB - OBJECTIVE: The purpose was to evaluate the articular cartilage of the hip joint with MR during traction and compare the findings with the resected specimen or arthroscopic findings. MATERIAL AND METHODS: Eight healthy volunteers, 5 patients with osteonecrosis, 5 with acetabular dysplasia, and 5 with advanced osteoarthrosis underwent MR imaging to evaluate the articular cartilage of the hip joint. Coronal fat-suppressed 3D spoiled gradient-echo (SPGR) images were obtained during traction. Identical imaging was performed of all the resected femoral heads of the osteonecrosis and advanced osteoarthrosis patients, and was correlated with the macroscopic pathological findings. RESULTS: The traction was effective and the femoral articular cartilage was clearly identified in all 8 control subjects, and in all cases of osteonecrosis and acetabular dysplasia. In 4 cases of osteonecrosis, chondral fracture was identified in the boundary between the necrosis and the normal area. In all cases of advanced osteoarthrosis, cartilage was identified only at the medial side. The MR images of osteonecrosis and advanced osteoarthrosis corresponded well with the MR images of the resected femoral heads and the macroscopic findings. CONCLUSION: Fat suppressed 3D-SPGR during continuous leg traction was useful in detecting cartilage abnormalities. PMID- 9973905 TI - MR imaging of lipoma and liposarcoma. AB - PURPOSE: To evaluate whether lipoma, atypical lipomatous tumors, and liposarcomas can be differentiated by MR images. MATERIAL AND METHODS: The MR images of 59 lipomatous lesions and liposarcomas were retrospectively reviewed. Apart from size, surgical site, location and margins, the percentage of fat of the tumor volume was assessed as none, 1-75%, 75-95%, or 95-100%. RESULTS: None of the 18 liposarcomas contained fat that could be recognized by MR imaging. The 3 atypical lipomatous tumors all contained fat but less than 75% of the tumor volume. In 32 of 38 ordinary lipomas, the percentage of fat was 95-100%, and in 4 less than 95% of the tumor volume. Two lipomas did not contain fat that could be recognized by MR imaging. CONCLUSION: A lesion which predominantly has a fat signal is, in all probability, an ordinary lipoma. Lesions with less fat, but still mostly fatty, may either be lipoma or atypical lipomatous tumor. In this group, the discrimination between these two entities cannot be based upon imaging features. In the absence of a fat signal, liposarcoma or lipoma cannot be differentiated from other soft tissue tumors. PMID- 9973906 TI - MR imaging in amyopathic dermatomyositis. AB - PURPOSE: Amyopathic dermatomyositis is a distinct clinical entity with cutaneous involvement but no myopathy. We conducted a prospective study to investigate the role of MR imaging in these patients. MATERIAL AND METHODS: Out of 40 Chinese patients presenting with dermatomyositis, based on clinical assessment and normal serum muscle enzymes 10 were diagnosed as having amyopathic dermatomyositis. These 10 patients underwent MR imaging for evaluation of any subclinical muscle involvement. RESULTS: Three patients demonstrated abnormal signal intensity in muscles on both T2- and fat suppression sequences. Thus, one-third of patients with dermatomyositis and clinically normal muscles may have detectable muscle inflammation on MR images, indicating that MR has a potential role for locating the relevant biopsy site and for longitudinal follow up. Six of the 10 patients had malignant disease diagnosed before or after diagnosis of the cutaneous manifestation. Nasopharyngeal carcinoma was the most common malignant disease in this group of patients. CONCLUSION: MR imaging is recommended for demonstrating subclinical muscle involvement in patients with the clinical diagnosis of amyopathic dermatomyositis. We also recommend screening for malignancy, particularly nasopharyngeal carcinoma, in Southern Chinese patients with dermatomyositis. PMID- 9973907 TI - Muscle metabolism of professional athletes using 31P-spectroscopy. AB - PURPOSE: The aim of the study was to examine muscle metabolism in athletes by 31P spectroscopy (MRS) and to evaluate to what degree the respective resonance spectrum correlates with the kind of muscle exercise. MATERIAL AND METHODS: Twelve runners and 12 young ice skaters were studied by 31P-spectroscopy of the gastrocnemic medialis muscle and the vastus medialis muscle using a surface coil at 1.5 T. RESULTS: Sprinters displayed a higher phosphocreatinine/inorganic phosphate (PCr/Pi) and PCr/beta-ATP ratios than marathon runners. The respective parameters for middle distance runners were in between. Ice skaters could prospectively be divided into sprint- and long-distance runners by our results which correlated with the athletes' training performance. CONCLUSION: 31P spectroscopy can evaluate the distribution of muscle fiber types. Thus, the athlete's potential for sprint- or long-distance running can be determined. Additional studies will have to demonstrate to what extent training may change muscle fiber distribution. PMID- 9973908 TI - MR findings in primary retroperitoneal schwannoma. AB - OBJECTIVE: To evaluate the MR findings in primary retroperitoneal schwannoma. MATERIAL AND METHODS: Seven cases of primary retroperitoneal schwannoma, in whom the diagnosis was confirmed histopathologically, were analyzed retrospectively. The following items were reviewed at MR imaging: tumor diameter, margin, homogeneity, signal intensity as compared to normal renal parenchyma, presence/absence of infiltration into adjacent organs, and, in 1 and 4 cases, the enhancement on Gd-dynamic images and post-contrast T1-weighted images, respectively. RESULTS: Tumor diameter was 5.5 +/- 3.1 cm, ranging from 2.5 to 10 cm in the 6 benign schwannomas, and 12 cm in 1 malignant. The tumor margin was regular in all of the benign cases and irregular in the malignant one. The malignant case showed infiltration into the liver and duodenum. Four of the benign schwannomas showed a homogeneous, and 2 presented a heterogeneous pattern, while the malignant schwannoma was heterogeneous. On T1-weighted images, the benign schwannomas were hypointense in 4 cases, isointense in 1 and mixed in 1, while on T2-weighted images, they were hyperintense in 5 and mixed in 1. The malignant case showed mixed intensity on both T1- and T2-weighted images. On enhanced T1-weighted images, capsular, septal enhancement was noted in 2 cases, overall enhancement in 2, and, on Gd-dynamic images, late enhancement was shown. CONCLUSION: On MR imaging, primary retroperitoneal schwannomas show different signal intensity characteristics, including cystic degeneration. There are, however, no specific characteristics of these tumors. PMID- 9973909 TI - Correlation of angiography and MR imaging in cerebral vasculitis. AB - PURPOSE: MR imaging and cerebral angiography were correlated in patients with primary angiitis of the central nervous system (PACNS) to assess the relative roles of these imaging modalities in the diagnosis. MATERIAL AND METHODS: In 9 patients, MR imaging and angiography were compared with regard to the relative involvement of each major vascular territory. Vascular territories assessed were the anterior, middle, and posterior cerebral arteries, and the posterior fossa. RESULTS: All patients had angiographic findings consistent with vasculitis in multiple vascular territories. MR findings ranged from normal to diffusely abnormal. One patient had a completely normal MR investigation. Of 50 territories affected by vasculitis on angiography, 17 (34%) were normal on MR. CONCLUSION: Relative to cerebral angiography, MR imaging is a poor indicator of the presence or absence of PACNS. Angiography is indicated when clinical suspicion of PACNS is strong, regardless of the findings on MR. PMID- 9973910 TI - Evaluation of the pituitary gland in idiopathic hypogonadotropic hypogonadism. AB - PURPOSE: Evaluation of the pituitary gland has been carried out in idiopathic hypogonadotropic hypogonadism (IHH) to test the potential of MR imaging in differentiating IHH patients from normals. MATERIAL AND METHODS: Thirty-seven patients (aged 18-30 years), and 20 volunteers (aged 20-30 years) were studied by T1-weighted MR imaging. Length (LA and LP), height (H), width (W), area (AA and AP), and volume (V1A, V1B V2A, V2P) of the pituitary gland were determined. (Subscripts P and A refer to measurements made with and without the posterior lobe, respectively.) V1 and V2 were estimated using two different methods. RESULTS: In the control group, LB W and V2A exhibited significant differences between female and male volunteers. While W was the only parameter that did not show significant difference between normals and patients (in both men and women), all other parameters except LB H and AP showed statistically significant differences between normals and IHH patients in both males and females. While LP was significantly different between normals and patients (men), H and AP were significantly different between normals and patients only in the female group. CONCLUSION: Correlation analysis between various parameters has shown that LA can be used for evaluating the pituitary in both the male and female IHH patients. PMID- 9973911 TI - MR myelography of sacral meningeal cysts. AB - PURPOSE: To describe the findings of sacral meningeal cysts (SMCs) on MR myelography and assess its value for the diagnosis of SMCs. MATERIAL AND METHODS: We evaluated the MR images and MR myelograms obtained from 10 patients with SMC. MR myelograms were obtained using a 2D or 3D single-shot fast spin-echo sequence. In 5 patients, X-ray myelograms and postmyelographic CT images were compared with the MR myelograms. RESULTS: A total of 33 SMCs were diagnosed within the spinal canal and/or sacral foramen. MR myelograms clearly revealed each cyst as a well defined mass showing hyperintensity (10 cysts) or isointensity (23 cysts) compared to cerebrospinal fluid. MR myelograms demonstrated SMCs better than X ray myelograms and postmyelographic CT images in 3 of the 5 patients. CONCLUSION: MR myelography can be an adjunct to conventional imaging techniques when surgical treatment is indicated, because it can precisely delineate the extent of SMCs. PMID- 9973912 TI - Transcatheter adrenal arterial embolization of cortisol-producing tumors. Two cases of Cushing's syndrome. AB - Transcatheter arterial embolization (TAE) was performed in 2 patients with Cushing's syndrome caused by adrenal adenoma by using a mixture of absolute ethanol and iohexol. In 1 patient successful suppression of the hypersecretion of cortisol has continued for 9 months after TAE without complications. However, in the other patient, TAE was discontinued due to marked hypertension and tachycardia induced by a massive release of catecholamines from the embolized "normal" part of the tumor-bearing adrenal gland during the procedure. These results suggest that it is important to perform TAE of only the arterial branches feeding the tumor. PMID- 9973913 TI - Accessory wandering spleen associated with short pancreas. A pediatric case report. AB - We present an extremely rare case of a 5-year-old girl with short pancreas associated with three accessory spleens, one of which was a large wandering spleen. The diagnosis was established by US and CT. A large accessory wandering spleen is considered to be at risk of torsion and infarction as well as susceptible to abdominal trauma. The authors discuss the difficulty of establishing the diagnosis and underline the importance of US and CT as pre operative diagnostic tools. PMID- 9973914 TI - Time dependence of iopamidol and iodixanol in arthrography of the knee. AB - PURPOSE: The safety and diagnostic efficacy of iodixanol (Visipaque) 270 mg I/ml was compared to that of iopamidol (Iopamiron) 300 mg I/ml in knee arthrography. MATERIAL AND METHODS: This trial was a bi-center double-blind trial including 128 patients (iodixanol/iopamidol 64/64 patients). Efficacy was evaluated by blinded grading of the diagnostic quality of the p.a. images taken 0, 12 and 25 min after contrast administration by the examining radiologist and later at a consensus evaluation by two experienced skeletal radiologists. Adverse events were recorded. RESULTS: No patient experienced any adverse event. The proportion of better images at both 12 and 25 min after injection was higher in the iodixanol group compared to the iopamidol group both by the examining radiologist and at the consensus evaluation. CONCLUSION: In the knee joint iodixanol is a safe contrast medium. The contrast effect of iodixanol lasted longer than that of iopamidol, which can be important when performing arthrography, especially CT arthrography, where the time between puncture and examination can be prolonged. PMID- 9973915 TI - Effects of iodixanol on renal function immediately after abdominal angiography. Clinical comparison with iomeprol and ioxaglate. PMID- 9973916 TI - Abnormal chromosome 8 copy number in stage I to stage IV breast cancer studied by fluorescence in situ hybridization. AB - To test the hypothesis that the frequency of abnormal chromosome 8 copy number increases with the severity of the disease as defined by an increase in clinical stage, we conducted a fluorescence in situ hybridization (FISH) study of a sample of 42 breast cancer specimens utilizing a protocol that was optimized by our laboratory. Cytogenetic results, obtained from blinded analyses of archival specimens, demonstrated that the higher clinical stages (i.e., stages III and IV) yield higher frequencies of abnormal chromosome 8 copy number. Specifically, 45.45% and 50% of the stage I and stage II cases, respectively, were abnormal, whereas 63.64% and 60% of the stage III and stage IV cases, respectively, were abnormal for chromosome 8 copy number. The overall frequency of abnormal chromosome 8 copy number was 54.76% (23 of 42 tumors studied). When the results of a control probe were taken into account, 34.78% (8 of 23) of the abnormal cases were trisomic, whereas the remaining cases were likely triploid. Thus, the present data not only established that chromosome 8 trisomy is a recurrent finding in breast cancer, but also confirmed a higher frequency of occurrence of abnormal chromosome 8 copy number with the higher clinical stages. Future experiments utilizing additional specimens in this laboratory and from other laboratories are necessary to confirm and extend the findings of the present study. PMID- 9973917 TI - Chromosomal aberrations during progression of chronic myeloid leukemia identified by cytogenetic and molecular cytogenetic tools: implication of 1q12-21. AB - To study the genomic abnormality underlying the acute transformation of chronic myeloid leukemia (CML), 15 CML patients in blast crisis (BC), 3 in accelerated phase (AP), and 20 in chronic phase (CP) were analyzed by conventional cytogenetics, comparative genomic hybridization (CGH), and dual-color chromosomal painting. Philadelphia (Ph) chromosome was identified in every case studied. Only 5 among 20 CP patients had additional abnormalities while 13 of 18 patients with disease progression (BC + AP) showed extra numerical and/or structural chromosomal aberrations. Cytogenetically, the most common chromosome gains during BC and AP were double or triple Ph chromosomes (5 of 14 cases) and trisomy 8 (5 of 14 cases). Trisomies 7 and 17 (1 of 14 cases each) were also observed. CGH analysis detected genetic imbalances in eight cases. Gains of chromosome 20 (3 cases) and 17q (2 cases) were observed, respectively. The recurrent chromosome loss was the deletion of the short arm of chromosome 17, seen in one case with i(17)(q10) and one case with an unbalanced translocation (1;17). In one case, a very complex chromosomal rearrangement, del(3),del(6),der(6)t(17;3;6),der(17)t(6;17), was seen. A novel finding of this work is the involvement of chromosome 1(q12-21qter) in CML disease progression. Overrepresentation of 1(q12-21qter) region was detected by CGH in one case which had a derivative chromosome 17. This abnormal chromosome was later confirmed by fluorescence in situ hybridization (FISH) painting to be a fusion between chromosome 1 and 17 to form the der(17)t(1;17) (q12-21;p11). Two other cases showed the same region being involved in translocations, t(1;10)(q12-21;q26) and t(1;11)(q12-21;p15). It is possible that one or more genes residing on chromosome 1q12-21 may be important in the acute transformation of CML. In conclusion, we find that the combined use of CGH, chromosome painting, and classic cytogenetic analysis allows a better evaluation of the genomic aberration involved in CML blastic transformation, and offers new directions for its further molecular investigations. PMID- 9973918 TI - Biclonal chromosomal aberrations in a child with myelodysplastic syndrome. AB - Hematological malignancies and premalignant diseases are generally of monoclonal origin. The prognostic and therapeutic significance of finding two genetically independent clones remains to be determined. We followed a case of childhood myelodysplastic syndrome showing biclonal chromosomal abnormalities (+8, -7) by conventional cytogenetic examination and double target fluorescence in situ hybridization (FISH). A 7-year-old girl presented with Plaut-Vincent angina and leukopenia. The cytogenetic aberration of +8 was the first sign to suggest MDS. Serial bone marrow controls, prompted by a progressive clinical course detected myelodysplastic changes and a new clonal aberration (-7). The presence of -7 and +8 in two independent clones was verified by double-target FISH. While at diagnosis and during cytokine treatment more cells showed +8, after successful all-trans retinoic acid (ATRA) therapy, the clone with -7 predominated. Following allogeneic bone marrow transplantation the patient displayed donor-derived hematopoesis. Our data stress the significance of cytogenetic and FISH examinations in detecting specific genetic abnormalities and progressive clonal changes as an indicator and guideline for therapy. Different cell clones characterized by different genetic changes might be associated with different biologic features reflected in their response to treatment. PMID- 9973920 TI - Study of chromosome 12 copy number in breast cancer using fluorescence in situ hybridization. AB - Trisomy 12 is the most frequent numerical chromosomal abnormality reported in chronic lymphocytic leukemia (CLL). Its significance in other cancers, however, has not been extensively investigated until recently. Less than 20 cases of polysomy for chromosome 12 have been studied thus far. The most recent data in the literature suggest that gain of chromosome 12 may be a recurrent and sometimes early event in breast carcinogenesis. To test the hypothesis that a subset of breast cancer may be characterized by chromosome 12 trisomy, we conducted a retrospective study of 40 specimens. Of these, ten were stage I, ten were stage II, ten were stage III, and ten were stage IV. Out of the total sample, 12 cases (30%) were found to be presumably trisomic, if a conservative cutoff point of greater than or equal to 15% cells with three signals is adopted. Furthermore, some, but not all, of the 12 cases were found to be likely triploid, when data from a control chromosome 17 probe were taken into account. Thus, our data support the hypothesis that a subset of breast cancer exists which is characterized by an abnormal copy of chromosome 12, in either a diploid or a triploid background. PMID- 9973919 TI - A combined cytogenetic and molecular approach to diagnosis in a case of desmoplastic small round cell tumor with a complex translocation (11;22;21). AB - Desmoplastic small round cell tumor (DSRCT) has recently been described as a discrete tumor entity. It is distinguished from other small round cell tumors by its prominent desmoplastic quality, its preponderance in adolescent males, its almost exclusive intraabdominal location, a multi-immunophenotypic profile, and its aggressive nature. Diagnosis on histology alone is not always unequivocal. A recurrent t(11;22)(p13;q12) translocation has recently been described in this tumor, and a chimeric RNA fusion product formed from the WT1 and EWS genes is detectable by reverse transcriptase-polymerase chain reaction (RT-PCR). We describe the use of a multi-faceted approach using conventional G-banding, fluorescence in situ hybridization (FISH) and RT-PCR to assist the diagnosis of a case of DSRCT with a complex variant t(11;22;21)(p13;q12;q22.1) translocation and demonstrate the value of a combined approach to genetic investigation of solid tumors. PMID- 9973921 TI - Replication pattern in cancer: asynchronous replication in multiple myeloma and in monoclonal gammopathy. AB - In this study we evaluated the replication pattern and cell-cycle dynamics of cells from patients considered to have a premalignant condition (monoclonal gammopathy, or MGUS) and patients with multiple myeloma (MM), as well as healthy controls. We applied the fluorescence in situ hybridization (FISH) technique with the TP53, RB-1 and 21q22 loci on the patient's cells. Asynchrony was determined by the presence of one single and one set of double dots in the same cell. The rate of asynchronic replication was significantly higher in the cells from MM patients, with intermediate value in the cells from MGUS, while the lowest rate was in cells from controls. We suggest that these results may reflect the changes in gene replication and cell-cycle progression that occur in premalignant and malignant cells. PMID- 9973922 TI - The contribution of deficient DNA repair to chromosomal radiosensitivity of CHO cells after G2 irradiation. AB - We compared cytogenetic responses of the parental Chinese hamster ovary (CHO) cell line and its DNA repair-deficient strains to irradiation during the G2 phase. Chromatid breaks were quantified in cells entering metaphase in the presence or absence of cytosine arabinoside (ara-C) 0.5-1.5 hours after exposure to x-rays or UV-C. Addition of ara-C, an inhibitor of DNA repair replication, significantly increased chromatid break frequency (CBF) in the parental line, but not in the strains deficient in nucleotide excision repair (NER). This increase (ara-C effect) was comparable to that in repair-proficient normal human lymphocytes. We conclude that CBF in cells entering metaphase in the presence of ara-C 0.5-1.5 hours after DNA damage represents a functional in vitro assay for evaluating the DNA repair capacity of mammalian cells in culture. PMID- 9973923 TI - Loss of heterozygosity of the TP53 tumor suppressor gene and detection of point mutations by the non-isotopic RNAse cleavage assay in prostate cancer. AB - Mutation within the TP53 tumor suppressor gene is a frequent occurrence in human cancers, resulting in a poor prognosis, response to therapy, and overall survival time. Mutations have been primarily detected in advanced prostate cancer; however, the involvement of the gene through loss of heterozygosity (LOH) in primary prostate cancers has not been investigated due to lack of identifiable polymorphisms within this gene. Using the nonisotopic RNAse cleavage assay (NIRCA), we screened for point mutations and identified an ApaI restriction site polymorphism located in intron 7 within the TP53 gene. This polymorphism allowed us to detect LOH in informative samples in a population of patients that underwent prostate biopsies and a population that underwent radical prostatectomies. Within the combined study population, 31 of 80 patients (38.75%) were informative for the polymorphism. Loss of heterozygosity was detected in 10 of the 31 samples (32.3%). Point mutations were identified in two samples. The identification of LOH in these patients suggests that the TP53 tumor suppressor gene may play a more active role in prostate cancer than was previously believed. PMID- 9973925 TI - Jumping translocation of 1q as the sole aberration in a case of follicular lymphoma. AB - Cytogenetic and fluorescence in situ hybridization (FISH) studies in a case of follicular lymphoma grade III showed a "jumping translocation" of chromosome 1q21 qter to chromosomes Xq28 and 18q23, which resulted in a partial trisomy 1q as the only chromosome aberration. This case represents, to the best of our knowledge, the first report of a jumping translocation in a malignant lymphoma occurring as the sole aberration. PMID- 9973924 TI - Involvement of MLL gene in a t(10;11)(q22;q23) and a t(8;11)(q24;q23) identified by fluorescence in situ hybridization. AB - We describe two cases of acute myeloblastic leukemia, classified as M4 and M5 in the French-American-British nomenclature, with an 11q23 rearrangement at karyotypic analysis. The involvement of the MLL gene with two new partner loci on chromosome 10q22 and 8q24, respectively, was demonstrated by fluorescence in situ hybridization using a YAC clone B22B2L. PMID- 9973926 TI - Cytogenetic analyses of 85 testicular germ cell tumors: comparison of postchemotherapy and untreated tumors. AB - Cytogenetic analyses of 85 testicular germ cell tumors, of which 54 were karyotypically abnormal, showed recurrent breakpoints at chromosome bands 1p36, 1p13-1qh, 11q23, 19q13, and the pericentromeric regions of the acrocentric chromosomes. Postchemotherapy tumors had significantly more rearrangements of bands 3p25-p26, 6q16-q21, 8p22-p23 when compared with untreated tumors, while untreated tumors had more rearrangements of 9p22-p24 when compared with postchemotherapy tumors. Frequent breakpoints also were identified at 15q15 and 9qh in untreated tumors. Tumors of different histopathology, clinical stage, and treatment status showed no significant differences in the frequencies of i(12p) positive and i(12p)-negative tumors. PMID- 9973927 TI - Near-haploidy in a malignant sacrococcygeal teratoma. AB - Cytogenetic analysis of a malignant sacrococcygeal teratoma in an adult patient revealed near-haploid (77%), near-diploid (19%), and polyploid (4%) cells. The near-haploid cells had a karyotype of 25,XX,der(5)t(5;7)(p15;p13),+7,der(9)t(6;9)(p21;q34),r(17)(p13q25) . In the near diploid and polyploid cells identical copies of the structural chromosomal changes were found. Although some of the anomalies observed appear unique to this case, a common breakpoint in chromosome 6 was previously reported as specific in a subgroup of extragonadal germ cell tumors of adults. PMID- 9973928 TI - Duplication of band 12q24 in acute myeloblastic leukemia. AB - Cytogenetic studies of two patients with acute myeloblastic leukemia, classified as M1 and M2, showed a partial duplication of the distal part of the long arm of chromosome 12 (12q24) as the sole detectable chromosome abnormality. High white blood cell count was common to the two leukemic children. Fluorescence in situ hybridization analysis with the use of a whole-chromosome 12 painting probe and a telomeric probe confirmed the apparent absence of any translocation. The genes involved in the duplication could not be ascertained, but several candidate genes such as growth-factor receptors or genes encoding transcription factors localized to 12q22-q24 should be investigated in the molecular analysis of these duplications. PMID- 9973929 TI - Karyotype evolution in a case of uterine angioleiomyoma. AB - Clonal karyotypic alterations of a uterine angioleiomyoma of a 41-year-old woman are reported. Cytogenetically a stemline of the tumor and two related subclones with additional abnormalities due to karyotypic evolution were identified: 46,X,t(X;11)(p11.4;p15)/46, idem,inv(2)(p15q13)/46, idem,inv(2)(p15q13),t(5;20)(q13;q13.2). None of the aberrations observed in the present case has been reported in uterine smooth muscle tumors before. PMID- 9973931 TI - Cytogenetic investigation in subependymoma. PMID- 9973930 TI - 3p13 region: a possible location of a tumor suppressor gene involved in uveal melanoma. AB - To contribute to a better understanding of the role of chromosomal rearrangements in the tumorigenesis of uveal melanoma, we present a case in which a structural aberration of chromosome 3 could indicate the specific region in which an uveal melanoma tumor suppressor gene could be located. We obtained a primary cell culture, characterized by cytogenetic study, through GTG- and CBG-banding techniques by using a mechanical dissection of a tumor sample obtained from an uveal melanoma. Cytogenetic analysis performed in the primary cell culture highlighted the presence of a structural rearrangement involving chromosomes 3 and 22. A t(3;22)(p13;p11) was observed as the only present clonal aberration. The 3p13 breakpoint involved in the aberration observed in our case could be essential in restricting the candidate region for the locus of an uveal melanoma tumor suppressor gene located on chromosome 3. PMID- 9973932 TI - Trisomy 12 resulting from isochromosomes of both 12p and 12q in a case of B-CLL. PMID- 9973933 TI - Cytogenetic findings in a malignant fibrous histiocytoma of the breast. PMID- 9973934 TI - Abnormalities in the p34cdc2-related PITSLRE protein kinase gene complex (CDC2L) on chromosome band 1p36 in melanoma. AB - The two genes encoding the PITSLRE protein kinase isoforms, CDC2L1 and CDC2L2, are localized to human chromosome band 1p36. The PITSLRE protein kinases are a part of the p34cdc2 supergene family. Several protein products of the CDC2L locus may be effector(s) in apoptotic signaling. The larger PITSLRE p110 isoforms appear to regulate some aspect of RNA splicing/transcription during the cell cycle. One or more of these genes may function as tumor suppressor genes in melanoma. Using fluorescence in situ hybridization, one allele of the CDC2L gene complex on chromosome 1 was either deleted or translocated in 8 of 14 different melanoma cell lines. We also observed mutations in the 5' promoter region of the CDC2L1 gene in four different cell lines relative to normal melanocytes using PCR SSCP analysis and direct DNA sequencing. Western blot analysis revealed decreased level of PITSLRE protein expression in several cell lines, as well as in four surgical malignant melanoma specimens relative to normal melanocytes. Thus, the decreased PITSLRE protein expression appears to result from deletion of the CDC2L alleles and possibly by mutations within the 5' promoter region. We propose that aberrations in the CDC2L genes may contribute to the pathogenesis or progression of melanoma. PMID- 9973935 TI - Validation of primed in situ labeling (PRINS) for interphase analysis: comparative studies with conventional fluorescence in situ hybridization and chromosome analyses. AB - Primed in situ labeling (PRINS) is a rapidly developing new technology with wide ranging clinical applications. To assess the sensitivity, specificity, and accuracy of PRINS, we carried out a retrospective study on cultured bone marrow cells to detect aneuploidy for chromosomes 7, 8, and 12. The results were then compared to the results of previous fluorescence in situ hybridization (FISH) and chromosome analyses (CA). In patients who showed aneuploidy with CA, both FISH and PRINS confirmed the aneuploidy in interphase cells. FISH and PRINS also showed excellent correlation with conventional cytogenetic analysis for the detection of mosaic aneuploidies. However, both FISH and PRINS showed significantly higher sensitivity in the detection of abnormal clones compared to CA. In 9 of the 17 cases, there were no significant differences in the detection rates between the two methods. Based on our studies, we conclude that PRINS is as sensitive as FISH in most cases for aneuploidy detection; and that PRINS, like FISH, is more sensitive than conventional CA for aneuploidy detection. PMID- 9973936 TI - Deletion of HMG17 in uterine leiomyomas with ring chromosome 1. AB - Uterine leiomyomas are characterized by several subgroups with characteristic chromosomal aberrations, mainly 12q14-15, 6p21, or interstitial deletions of chromosomes 3 and 7. For the first two subgroups, aberrations of the HMGIC and HMGIY genes have been described and are held responsible for tumor initiation. For other subgroups no molecular findings have been described as of yet. We focus here on a smaller subgroup of uterine leiomyomas with a ring chromosome 1 either as the only karyotypic deviation or occurring along with other abnormalities. In the p-arm of chromosome 1 HMG17, another member of the high-mobility group of proteins has been localized to the short arm of chromosome 1 (1p35) with two PAC clones on metaphase spreads of a uterine leiomyoma ring(1). Hybridization signals for these probes were not detected within the ring chromosome consistent with loss or deletion of HMG17. These findings suggest that HMG17 does not play a mechanistic role in leiomyoma similar to that observed with other high-mobility proteins. PMID- 9973937 TI - A combined approach of conventional and molecular cytogenetics for detailed karyotypic analysis of the small cell lung carcinoma cell line U2020. AB - Until recently the ability to analyze complex karyotypic rearrangements was totally dependent upon light microscopy of G-banded chromosomes. Developments in the area of molecular cytogenetics have revolutionized such analysis, making it possible to determine the nature of complex rearrangements. An extensive analysis has been made of the small cell lung carcinoma (SCLC) cell line U2020, using a combined approach of conventional and molecular cytogenetics, enabling a highly detailed karyotype to be constructed revealing rearrangements previously undetected by G-banding alone. This approach offers the opportunity to reassess other tumor karyotypes, particularly those of high complexity found in solid tumors, for tumor-specific consistent rearrangements indecipherable by conventional karyotyping. PMID- 9973938 TI - Deletion of cell division cycle 2-like 1 gene locus on 1p36 in non-Hodgkin lymphoma. AB - Our laboratories have documented a significantly high occurrence of chromosome 1p36 rearrangements in non-Hodgkin lymphoma (NHL). The cell division cycle 2-like 1(CDC2L1) (also known as TP58 or PITSLRE) gene, a protein kinase implicated in apoptotic signaling, is located at the very distal region of chromosome 1p36 and is likely to be disrupted by structural rearrangements involving 1p36. To determine the molecular consequences of the recurrent involvement of the 1p36 region, we examined metaphases containing 1p36 abnormalities from 31 specimens derived from 26 patients for the possible deletion of CDC2L1 by fluorescence in situ hybridization (FISH) using the TP58clk-1 DNA probe. Twenty-three cases exhibited the loss of CDC2L1 from the abnormal chromosome 1. In 2 of 26 cases, the gene locus was translocated to the partner chromosome, and in four specimens, all derived from one case, CDC2L1 was not deleted. This pilot investigation suggests that 1p36 rearrangements, and consequently the loss of the CDC2L1 gene locus, is important in NHL. This work also opens avenues for further molecular studies and prognostic correlations. PMID- 9973939 TI - Trisomy 8 in embryonal rhabdomyosarcoma detected by fluorescence in situ hybridization. AB - Embryonal rhabdomyosarcoma is the most common malignant soft-tissue tumor in childhood. Cytogenetic studies of this tumor are rare. In one study trisomy 8 was found to be a primary cytogenetic abnormality. In view of the findings of trisomy 8 in a multitude of cancers, we conducted a pilot study to test the hypothesis that a subset of rhabdomyosarcoma also exists with trisomy 8. Accordingly, archival tissues of 12 cases of rhabdomyosarcoma were retrieved and fluorescence in situ hybridization (FISH) using a chromosome 8-specific, alpha-satellite probe was undertaken on formalin-fixed paraffin-embedded tissue sections using the protocol optimized in the Cytogenetics Laboratory at Rhode Island Hospital. The results obtained demonstrated that 6 of 12 tumors showed chromosome 8 trisomy, when a 15% threshold is adopted. In addition, one case was borderline, with 11% of the cells found positive for three fluorescent signals. Future experiments utilizing additional specimens from our centers as well as from other laboratories are needed to confirm and extend the findings of the present study. PMID- 9973940 TI - Analysis of sperm chromosome complements before, during, and after chemotherapy. AB - Sperm chromosomal abnormalities were assessed in testicular cancer patients before, during, and after BEP (bleomycin, etoposide, cisplatin) chemotherapy (CT). Multicolor fluorescence in situ hybridization (FISH) analysis was employed to detect aneuploidy for chromosomes 1, 12, X, and Y, and diploidy. Sperm samples were cryopreserved and coded before analysis to facilitate "blind" analysis. Complete results at all time points was available for only one patient. A total of 60,400 sperm were analyzed: 20,004 before CT, 20,005 during CT, and 20,391 after CT. There was a significant increase in the frequency of 24,XY sperm during (0.33%) and post-CT (0.34%) compared to pre-CT (0.14%). This study suggests that there may be a significantly increased risk of chromosomal abnormalities in sperm of CT patients during and immediately post-CT, similar to that shown in animal models. PMID- 9973941 TI - Trisomy 7 and trisomy 8 in dividing and non-dividing tumor cells in Dupuytren's disease. AB - Cytogenetic and molecular cytogenetic analysis is reported in a series of 40 tissue samples from 36 patients with Dupuytren's disease, presenting as palmar and/or finger nodules. No consistent structural chromosome changes could be found. Instead, recurrent clonal numerical abnormalities were demonstrated in 22 of 40 tissue nodules, involving trisomies of chromosome 7 or 8 and loss of the Y chromosome. In addition, we showed that trisomy 7 and trisomy 8 were also present in non-dividing cells. PMID- 9973942 TI - Plexiform fibrohistiocytic tumor with a clonal cytogenetic anomaly. AB - Plexiform fibrohistiocytic tumors are rare lesions of proposed myofibroblastic origin occurring primarily in infants and children. There is a characteristic biphasic histology comprised of both fibroblastic and histiocyte-like components. These tumors tend to be locally aggressive with prognosis dependent on completeness of resection. A previous cytogenetic case report of this tumor described a stemline clone with a karyotype of 46,XY,-6,-8, del(4)(q25q31),del(20)(q11.2),+der(8)t(8;?) (p22;?),+mar. We report a different cytogenetic finding in another plexiform fibrohistiocytic tumor which demonstrated a simpler karyotype of 46,XY,t(4;15)(q21;q15). The implications of cytogenetic heterogeneity in fibroblastic tumors is briefly discussed. PMID- 9973943 TI - A case of childhood acute myeloid leukemia associated with inversion (7)(p21q31). AB - We describe a case of acute myeloid leukemia in a 2 1/2-year-old boy presenting with a mediastinal tumor causing respiratory distress, and lymph node enlargement in the cervical and inguinal regions. Apart from myeloid markers CD13 and CD33, blast cells also expressed stem cell marker CD34 and megakaryocytic marker CD61. Cytogenetically, inv(7)(p21q31) was found in 9/25 and 15/25 analyzed metaphases from short-term cultures of lymph node and bone marrow cells, respectively. The patient is in continued complete remission 26 months post diagnosis. The case demonstrates that chromosome aberrations other than inv(16), t(8;21), and t(9;11) may be associated with extramedullary disease, and that not all chromosome 7 aberrations are prognostic adverse findings. PMID- 9973944 TI - Jumping translocations of 3q in acute promyelocytic leukemia. AB - Jumping translocation is a rare phenomenon, seldom reported to occur in cancer. A complex four-way translocation involving chromosomes 3, 9, 15, and 17 was identified in the chromosome study on a patient with a history of an acute promyelocytic leukemia (APL). In the follow-up studies, the same complex rearrangement exhibited a jumping translocation between chromosomes 3 and 9 in one clone and 3 and 6 in another clone. This is the first reported case of jumping translocation in APL. PMID- 9973945 TI - Bleomycin-induced chromosome aberrations in lymphocytes derived from patients with lamellar ichthyosis. AB - Patients affected by some genetic skin defects, for example, dyskeratosis congenita or scleroderma, may present spontaneous or induced chromosomal fragility. Hence we performed a cytogenetic analysis in families of patients affected by lamellar ichthyosis, an autosomal recessive disease not yet fully characterized at the cellular and molecular levels. Chromosomal fragility was assayed in untreated lymphocyte cultures and in those supplemented with aphidicolin or bleomycin. Cells from some affected patients and some of their parents showed hypersensitivity to the radiomimetic agent bleomycin. PMID- 9973946 TI - Amplification of BCR-ABL rearrangement in atypical Philadelphia chromosome: a new variant detected by fluorescence in situ hybridization in one case of acute lymphoblastic leukemia. AB - We report on a 67-year-old woman with acute lymphoblastic leukemia (ALL) who was supposed to have a variant Philadelphia (Ph) translocation identified by conventional cytogenetic techniques. Fluorescence in situ hybridization (FISH) analysis demonstrated the presence of an amplification of BCR-ABL rearrangement at locus 22q11. This is the first observation, to our knowledge, of a duplicated BCR-ABL chimeric gene within the derived chromosome 22 in ALL. Our observation supports the possibility of detecting a variant Ph chromosome at the single-cell level by FISH analysis. PMID- 9973947 TI - Elliptocytosis in myelodysplastic syndrome associated with translocation (1;5)(p10;q10) and deletion of 20q. AB - Acquired elliptocytosis is a red blood cell abnormality occasionally associated with myelodysplastic syndrome (MDS). A Japanese male with MDS who presented with elliptocytosis had mild anemia and hypercellular bone marrow with three lineage dysplasia. He was diagnosed with refractory anemia of MDS. Cytogenetic analysis of bone marrow cells showed 47,XY,+1,der(1;5)(q10;p10),t(1;5) (p10;q10),del(20)(q11) in 70% of the analyzed cells. Analysis of red blood cell membrane proteins by sodium dodecyl sulphate-polyacrylamide gel electrophoresis showed normal electrophoretic patterns with no quantitative abnormalities of each protein. Del(20q) and/or t(1;5)(p10;q10) might be associated with elliptocytosis in this patient. PMID- 9973948 TI - Increased karyotype precision using fluorescence in situ hybridization and spectral karyotyping in patients with myeloid malignancies. AB - We studied seven patients with various malignant hematologic disorders using fluorescence in situ hybridization (FISH) and one of these patients with spectral karyotyping (SKY). With appropriate probes, the t(8;21) and inv(16) were confirmed in two patients and the karyotypic precision was increased in five others using FISH and SKY. Two of three patients with 12p rearrangements had a deletion of one TEL allele. Thus, these newer techniques are an important adjunct to accurate chromosome analysis in malignancy. PMID- 9973949 TI - Simultaneous occurrence of chronic myelogenous leukemia and non-Hodgkin lymphoma at diagnosis. AB - We describe a case with the simultaneous occurrence of chronic myelogenous leukemia (CML) and non-Hodgkin lymphoma (NHL). Peripheral blood (PB) and bone marrow (BM) smears showed typical CML features. Lymph node biopsy exhibited a large-cell NHL. The Philadelphia chromosome or its molecular counterpart, the BCR ABL gene fusion, by detecting with dual color-(DC) fluorescence in situ hybridization (FISH), was detected reliably both in metaphase spreads from BM and in interphase nuclei from BM and follow-up PB cells, but was not detected in the lymph node cells. Clinical features and laboratory findings show this case having a coexistence of CML and NHL. PMID- 9973950 TI - Trisomy 10 as a sole chromosomal abnormality in AML-M2. PMID- 9973951 TI - Trisomy 8 and trisomy 14 in plantar fibromatosis. PMID- 9973952 TI - Predictive value of the polymerase chain reaction for the partially duplicated MLL gene transcript in acute myeloid leukemia. PMID- 9973954 TI - A multimodal approach in the diagnosis of patients with hematopoietic disorders. AB - Myelodysplastic syndromes (MDS) are a group of relatively ill-defined hematopoietic disorders in which both qualitative and quantitative defects of the hematopoietic cells cause bone marrow dysfunction. With an incidence estimated to be approximately 1 per 100,000 persons per year, MDS mainly affects the elderly. Myelodysplastic syndromes share many features with acute nonlymphocytic leukemia; in fact, a proportion of patients with MDS eventually develop acute myeloid leukemia. To illustrate a multimodal approach in the diagnosis of patients with hematopoietic disorders, we describe a 66-year-old patient with a question of myelodysplastic syndrome, leukemia, and two translocations involving chromosome 10:t(5;10) and t(7;10). These structural rearrangements effectively gave rise to monosomy for part of the long arm of chromosome 5 and for the long arm of chromosome 7. Findings of del(5q) and del(7) in MDS have been reported in the literature. The results of chromosome morphometry, which was conducted to compare the lengths of all relevant chromosome segments, are consistent with the hypothesized chromosomal abnormalities. The investigational technique of fluorescence in situ hybridization (FISH), using both painting and alpha satellite probes, was used as an adjunct to conventional cytogenetics to further delineate the nature of the chromosome abnormalities observed in the GTG-banded studies. Confirmatory studies utilizing the new technique of spectral karyotyping (SKY) were also carried out. Thus, the multimodal approach of hematopathology, GTG-banding, chromosome morphometry, FISH, and SKY can be very useful for delineating complex cytogenetic cases. PMID- 9973953 TI - High rate of chromosomal abnormalities in HTLV-I-infected T-cell colonies derived from prodromal phase of adult T-cell leukemia: a study of IL-2-stimulated colony formation in methylcellulose. AB - To detect chromosomal abnormalities in prodromal phase of adult T-cell leukemia (ATL), we established a clonal culture method for human T-lymphotropic virus type I (HTLV-I) infected T-cells in methylcellulose containing recombinant human interleukin 2 (rhIL-2). We tried to analyze chromosomes of 187 colonies (4, 23, 69, 74, and 17, from HTLV-I-uninfected normal T-cells, HTLV-I-Infected normal T cells, HTLV-I carriers, smoldering ATL, and chronic ATL, respectively), using chromosomal banding methods. In the prodromal group, 53% of colonies (84/160) (36/69, 37/74, 11/17 in HTLV-I carriers, smoldering ATLs, and chronic ATL, respectively) had chromosomal abnormal clones. In HTLV-I carriers, multiple clones with simple chromosomal abnormalities were observed. In more progressed chronic ATL, more complex chromosomal abnormalities were detected, and specific colonies were selected. Thus, colonies in the prodromal phase of ATL are characterized by cytogenetical clonal evolution and clonal changes. PMID- 9973955 TI - Deletion 7q in B-cell low-grade lymphoid malignancies: a cytogenetic/fluorescence in situ hybridization and immunopathologic study. AB - Ten cases presenting a simple karyotype and del(7q) as a primary event were selected out of 353 patients referred as B-cell low-grade malignant lymphoproliferative disorders. Chromosome 7-specific painting probes confirmed the deletion that was tentatively assigned to bands q31q35. Chromosome 7 was involved in an interstitial deletion in seven cases, in an unbalanced translocation in two cases, and in a ring chromosome in one case. Common clinical/hematological features included advanced age, marked splenomegaly, and peripheral blood monoclonal IgM(D) lymphocytosis. Regardless of morphologic entity, most cases shared lymphoplasmacytoid features. Deletion 7q may delineate a variety of low-grade B-cell lymphoid disorders characterized by a common clinical history and immunopathologic similarities. The cytogenetic pattern and the ongoing work on molecular mapping of this deletion suggest that the loss of a putative tumor-supressor gene at 7q31q32 may constitute an early event in their pathogenesis. PMID- 9973956 TI - Cytogenetic changes in two cases of subependymal giant-cell astrocytoma. AB - Cytogenetic analysis of subependymal giant-cell astrocytomas (SEGAs) from two patients presenting the clinical symptoms of tuberous sclerosis complex (TSC) revealed clonal chromosomal changes, resulting in the partial loss of chromosome 22q in both tumors. Immunohistochemically, tumors exhibited features of glial differentiation, while ultrastructural studies identified the characteristic paracrystalline inclusions within the tumor cells. To our knowledge, it is the first cytogenetic description of SEGAs associated with TSC. PMID- 9973957 TI - Frequent hypomethylation in Wilms tumors of pericentromeric DNA in chromosomes 1 and 16. AB - Rearrangements in the pericentromeric heterochromatin of chromosome 1 or 16 are often found in many types of cancers, including Wilms tumors, and have been suggested to contribute to oncogenesis or tumor progression. The oncogenic potential of these rearrangements has been ascribed to the resulting chromosome arm imbalances affecting the dosage of tumor suppressor genes or protooncogenes. Because DNA hypomethylation has been linked to rearrangements in the pericentromeric regions of chromosome 1 and 16 in two types of non-cancer cell populations, we examined methylation of normally highly methylated satellite DNA sequences in these regions in Wilms tumors. Hypomethylation was found to be frequent in juxtacentromeric (satellite 2) sequences and, especially, in centromeric (satellite alpha) sequences of chromosome 1. Hypomethylation of satellite 2 DNA of chromosome 16 showed a high degree of concordance with that of satellite 2 DNA of chromosome 1. We discuss the relationship of this satellite DNA hypomethylation in Wilms tumors to chromosome aberrations, as determined by assays for loss of heterozygosity. PMID- 9973959 TI - Pathological and karyotypic abnormalities in advanced gastric carcinomas. AB - Twenty samples of stomach cancers were analyzed by conventional cytogenetic and histopathological techniques. Nineteen tumors were diagnosed as adenocarcinomas and one as an adenosquamous carcinoma. Multiple and complex chromosomal abnormalities were found in the cases evaluated cytogenetically. This heterogeneity of chromosomal changes appears to indicate a certain correlation with tumor progression. Histological analysis showed a distinctive growth pattern of gastric cancer samples and a potential for invasiveness and recurrence for all tumors as well as a poor prognosis. PMID- 9973958 TI - Jumping translocation of homogeneously staining region and tetraploidy with double minutes in acute myelomonocytic leukemia. AB - We report a 71-year-old patient with acute myelomonocytic leukemia (AMMoL) who had complicated chromosomal abnormalities showing diploidy with a jumping translocation of a homogeneously staining region (hsr) and tetraploidy with double minutes (dmin). The analysis of gene amplification showed that hsr and dmin were the results of C-ETS 1 gene amplification. After induction chemotherapy, tetraploidy with dmin completely disappeared, while diploidy with hsr and del(11)(q23) remained until the patient died. It is speculated that hsr is more stable than dmin during chemotherapy and that the presence of tetraploidy is not necessarily a factor of poor response to chemotherapy for acute leukemia. PMID- 9973960 TI - Can genetic instability be studied at the single chromosome level in cancer cells? Evidence from human melanoma cells. AB - We evaluated whether genetic instability, which is the hallmark of cancer cells, can be investigated at the single chromosomal level. We established in culture and examined a human malignant melanoma cell line and its 11 distinct clones as well as peripheral blood cultures from the original patient by G-banding, C banding, and silver-staining (AgNOR) techniques. There were six marker chromosomes common to most of the 11 clones and eight or nine additional marker chromosomes found in only one or in very few clones. Chromosome 1 had a pericentric inversion in the C-banded region in both the tumor and the lymphocyte metaphase spreads. This same homologue was also involved in the formation of one of the shared marker chromosomes; this marker, in turn, was rearranged to form two unique markers in one clone. Our findings suggest that genetic instability can be studied at the single chromosome level. Moreover, this study further supports our earlier contention that peripheral blood lymphocyte cultures can show chromosomal lesions that are stable markers in cancer cells. PMID- 9973961 TI - Adult precursor-B acute lymphoblastic leukemia with translocations involving chromosome band 19p13 is associated with poor prognosis. AB - Cytogenetic translocations involving chromosome band 19p13, the site of the E2A gene, have previously been reported in pediatric acute lymphoblastic leukemias (ALL) in association with a precursor-B cell immunophenotype and poor prognosis. We studied the frequency, pathologic findings, and clinical course of adults with leukemia with 19p13 translocations. Six patients with t(1;19) (q23;p13) and one patient with t(17;19)(q21;p13), all with ALL, were identified over an 8-year period from among 183 adult ALL patients (2.7%); t(1;19) was observed in 2.2% and t(17;19) in 0.5% of these patients. The seven patients (four females and three males) ranged from 18 to 59 years of age (median 33). All cases had a precursor-B cell immunophenotype, and a distinctive expression of surface markers (CD10, CD19, TdT, and HLA-Dr positive, usually negative for CD20, CD34, and negative for myeloid-associated antigens CD13, CD14, and CD33). The blast cells in one case expressed CD15. All patients were treated with combination chemotherapy and three patients received allogeneic bone marrow transplantation. All patients had early (range 6-20 months) relapses, and died due to progressive disease 7-29 months after diagnosis. Similar to pediatric patients, adults with 19p13 leukemias usually do not respond to intensive therapy and have short survival. The poor prognosis of this group of adult ALL patients highlights the importance of detecting 19p13 translocations by cytogenetic analysis or molecular studies. PMID- 9973962 TI - Limited nonrandom chromosomal aberrations in a recurrent adenoid cystic carcinoma of the parotid gland. AB - We present the cytogenetic, interphase fluorescence in-situ hybridization (FISH) and DNA content findings in a clinically aggressive adenoid cystic carcinoma (ADCC) of the parotid gland. The tumor manifested diploid chromosomal and DNA content by cytogenetic, interphase FISH and flow cytometry. G-banding analysis revealed inv(5)(p15.2q33) and t(6;15)(q25;q15) as the only structural alterations in all 30 metaphases examined. The limited structural abnormalities found in this recurrent lesion suggest that they may constitute a primary or early event in the development of this tumor. The involvement of 6q region in our tumor and in some of the previously reported ADCC supports the association between this region and the evolution of at least a subset of these tumors. PMID- 9973964 TI - Complex translocation (6;21;8), a variant of t(8;21), with trisomy 4 in a patient with acute myelogenous leukemia (M2). AB - The t(8;21)(q22;q22) is the second-most frequently observed nonrandom karyotypic abnormality associated with acute myelogenous leukemia (AML), especially in FAB M2. Trisomy 4 is also a specific chromosomal abnormality for AML FAB M2 or M4. We experienced a 37-year-old woman with a morphologically AML FAB M2 carrying a rare complex translocation (6;21;8)(p21;q22;q22) resulting in AML1 gene rearrangement. A subclone with an additional chromosomal abnormality, trisomy 4, was also revealed. Similarly to the typical t(8;21), a conventional chemotherapy successfully induced into complete remission associated with a recovery of normal karyotype, 46,XX, although AML1/MTG8 (ETO) chimera mRNA was detected by reverse transcriptase polymerase chain reaction. PMID- 9973963 TI - Inversion (6)(p23q15) as the sole anomaly in a low-grade intraosseous osteosarcoma. AB - We describe the finding of an inversion (6)(p23q15) as the sole anomaly in short term cultures from an intraosseous low-grade osteosarcoma. PMID- 9973965 TI - Double minute chromosomes in a patient with myelodysplastic syndrome transforming into acute myeloid leukemia. AB - Presence of double minute chromosomes (dmin) is rare in bone marrow cells in patients with preleukemia and leukemia. We describe a case of myelodysplastic syndrome-refractory anemia with excess of blasts (MDS-RAEB) associated with two unrelated pathological chromosomal clones that developed during the progression of the disease. The patient was followed cytogenetically for a period of 4 years. At the time of transition into RAEB-T and later to acute myeloid leukemia (AML), dmin were associated with resistance to chemotherapy. Fluorescence in situ hybridization study proved that the dmin in this case were c-MYC amplicons. At the terminal stage of the disease, dmins were present in all 50 analyzed cells. PMID- 9973966 TI - No chromosomal instability in offspring of survivors of childhood malignancy. AB - Chromosomal instability was examined in 20 apparently healthy children of survivors of childhood malignancy. As compared to controls, no increase of spontaneous or bleomycin-induced aberrations (including gaps, breaks, sister chromatid exchanges, pulverization, and premature centromere divisions) were found in these "index children." The results suggest that the offspring of subjects previously receiving chemotherapy and/or radiotherapy for childhood malignancy are probably at no increased risk of latent chromosomal instability. PMID- 9973967 TI - Identification of a ring chromosome in a myxoid malignant fibrous histiocytoma with chromosome microdissection and fluorescence in situ hybridization. AB - We investigated the origin of a ring chromosome in a myxoid malignant fibrous histiocytoma (MFH) by microdissection and fluorescence in situ hybridization (FISH) analyses. Cytogenetically, only two ring chromosomes were observed; the smaller ring was seen more frequently. The latter was microdissected, and the material used for FISH. Hybridization of the microdissected labeled DNA to normal metaphase cells revealed that the signal localized only to 20q. Three signals were seen in the tumor cells using either the microdissected 20q probe or chromosome 20 centromeric probe, indicating the involvement of both the long arm and the centromere in the ring chromosome. The short arm of chromosome 20 did not appear to be involved in the formation of the ring chromosome. PMID- 9973969 TI - Trisomy 10 in acute myeloid leukemia: revisited. PMID- 9973970 TI - Interscapulo-thoracic resection for malignant tumors of the shoulder joint region. 1928. PMID- 9973971 TI - Endoprosthetic replacement for primary malignant tumors of the proximal femur. AB - Fifty-four patients had endoprosthetic replacement of the proximal femur after resection of primary malignant or aggressive bone tumors. The mean age of the patients was 41 years. The average duration of followup was 9 years (range, 5-24 years). At the time of this review 35 patients are surviving. There were six revisions of the acetabulum and seven revisions of the femoral component. The survivorship of the prostheses without revision was 77% at 10 years falling to 57% at 20 years. There was a 13% risk of amputation and a 1.8% incidence of infection. The mean of the functional scores of the 35 living patients was 83% (range, 60%-97%). This study showed that successful long term results can be obtained with cemented massive endoprostheses despite the incidence of recognized complications including polyethylene wear and aseptic loosening. PMID- 9973968 TI - Translocation (17;22)(q22;q13) in a case of subcutaneous dermatofibrosarcoma protuberans in an adult. PMID- 9973972 TI - Algorithm for the surgical treatment of malignant lesions of the proximal tibia. AB - Complications are common among patients treated for malignant lesions of the proximal tibia and can be difficult to manage. This investigation was a retrospective review of 40 patients treated with total knee replacements after proximal tibial resections. Various reconstructive methods were used to fix the prosthetic stems, reestablish the extensor mechanism, and provide soft tissue coverage. Thirty-one patients had adequate followup to allow for review of prosthetic outcome (means, 78 months; range, 25-193 months). Seven patients died with less than 2 years followup, and two patients had postoperative acute infections treated by early amputation to allow chemotherapy to resume promptly. The overall 5-, 8-, and 12-year event free prostheses survival rates were 62%, 33%, and 16%, respectively. Prognostic factors for prosthetic survival were analyzed (age, gender, type of excision, type of prosthesis, type of fixation, and percent of bone resected). None were statistically significant. Patients with less than 40% of the tibia resected had better prosthetic survival at 5 years. The durability of uncemented stem fixation exceeded that of cemented stems. Expected survival of prostheses after revision was 52% at 8 years. The major cause of limb loss was infection. Failure to reconstruct soft tissues satisfactorily caused most failures. Aggressive multistage management of infection is needed. Prosthetic knee replacement is most suitable for patients with cancers that require chemotherapy and for those patients who have short potential survival. PMID- 9973973 TI - Marginal excision for osteosarcoma with caffeine assisted chemotherapy. AB - The authors report on intentional marginal excision for osteosarcoma in conjunction with caffeine assisted chemotherapy for the purpose of preservation of good limb function. Twenty-seven patients with osteosarcoma (22 patients with Stage IIB and five with Stage IIIB) preoperatively were given three-to-five courses of intraarterial cisplatin and caffeine without or with doxorubicin. For 26 (96%) responders to the chemotherapy, limb salvage surgery was conducted by means of an intentional marginal procedure, which led to the preservation of important structures such as major neurovascular bundles, tendons, ligaments, muscles, and the epiphysis. Tumors were located in the distal femur in 11 patients, the proximal tibia in eight, the proximal fibula in four, the proximal humerus in two, and the proximal femur in one patient. The histologic response of these 26 patients to the preoperative chemotherapy showed no viable cells in 19 patients with Stage IIB osteosarcoma and only scattered foci of viable cells in two patients with Stage IIB and five patients with Stage IIIB osteosarcoma. As for reconstruction, distraction osteogenesis was performed in eight patients, allograft or autoclaved bone and prosthesis composite in four, autoclaved bone in two, osteochondral allograft in two, megaprosthesis in six, and resection alone in four patients. The average functional evaluation of the 26 patients was 91% of normal. Local tumor recurrence was seen in one patient, whereas 18 patients with Stage IIB osteosarcoma remain diseasefree with a mean followup of 61 months. Two patients with Stage IIB osteosarcoma and four patients with osteosarcoma Stage IIIB died of the disease. Intentional marginal excision for osteosarcoma in conjunction with caffeine assisted chemotherapy is advantageous because it results in the preservation of healthy important structures, with joint preservation possible in selected cases. This approach should help to improve the success rate of limb salvage surgery for osteosarcoma and to preserve the function of the affected limb. PMID- 9973975 TI - Long-term results of limb salvage with the Fabroni custom made endoprosthesis. AB - In 1972 the authors began working on a limb amputation method using custom endoprostheses. Because of the biomechanical characteristics of these prostheses, good long-term results have been achieved. The current study presents the analysis of 27 cases, including 11 total femoral replacements, with a followup between 10 to 24 years (median, 14.4 years), with an overall score of 75% using the International Symposium On Limb Salvage evaluation system. Analyzing this surviving group, the authors realize that proximal humerus and proximal femur prosthesis with total or partial joint replacement have better scores of prosthetic survival, limb function, and patient acceptance and the lowest rates of mechanical complications. However, the replacement involving the knee had more complications and worse scores. The authors conclude that the simplest prosthetic design implanted had the fewest intrinsic prosthetic complications. Reducing the stiffness of a prosthesis and increasing the range of movement of the joint involved decreasing the stress forces between the prosthesis and the bone. This may have contributed to the favorable outcomes reported in the series. PMID- 9973974 TI - Long-term followup of patients with autogenous resection arthrodesis of the knee. AB - Arthrodesis of the knee may be indicated for the reconstruction after resection of tumor around the knee. Since the introduction of this technique, resection arthrodesis using segmental autogenous grafts has been the principal method of reconstruction. From August 1967 to February 1985, 73 patients underwent resection arthrodesis using autogenous grafts. All procedures were performed for malignant or potentially malignant lesions. Ten-year followup was available on 40 patients. The reconstructive procedure was performed using an intramedullary rod and hemicortical femoral or tibial grafts with a single autogenous nonvascularized fibula or with dual nonvascularized fibulae. Despite a high surgical complication rate, the majority of patients achieved successful limb salvage. Independent ambulation was achieved by 86% of the patients. A Musculoskeletal Tumor Society functional evaluation in 32 available patients at a mean of 17 years showed the majority of patients functioning satisfactorily. Long term followup of these patients shows continued durability of the reconstruction and a persistent high level of function and patient satisfaction. Resection arthrodesis using massive autogenous grafts should continue to be in the armamentarium of the orthopaedic oncologist. PMID- 9973976 TI - Reoperation for failed prosthetic replacement used for limb salvage. AB - Patients with segmental bone and joint replacement prostheses because of tumors increasingly need revision surgery because of their long term survival. Between 1970 and 1990, 208 custom prosthetic replacements were performed for limb salvage in patients with tumors. Reoperations were required in 52 patients. The mean time to reoperation was 37 months. The reoperation procedures included 35 prosthetic revisions, 11 amputations, four arthrodeses, one vascularized fibular graft, and one open reduction and internal fixation of a fracture with supplemental bone graft. Functional assessment using the new Musculoskeletal Tumor Society scoring system was available for the 36 living patients, and their mean rating was 63% (18.9) at 12 years' mean followup. Of the 35 patients who received a new prosthesis, 12 (33%) patients needed a third operation at mean followup of 68 months. The probability of prosthetic survival in the group of 35 patients needing revision to the same or another prosthesis was 79% at 5 years and 65% at 10 years. The chance and frequency of needing reoperation increased as patients survived longer. Reoperations for tumor recurrence or infection usually resulted in amputation. Reoperation for failed initial segmental bone and joint prosthetic replacement is feasible and effective and can be done without jeopardizing subsequent patient and implant survival or without significantly affecting functional results compared with the values before reoperation. PMID- 9973977 TI - Etiology and results of tumor endoprosthesis revision surgery in 64 patients. AB - From December 1980 to December 1995, 278 patients underwent primary custom endoprosthesis replacements for neoplastic disease at the University of California, Los Angeles and have been followed up for a minimum of 2 years or to death. The endoprosthesis reconstruction failed in 64 patients, including 10 additional patients referred for revision of their replacements. Failure was defined as the complete removal of a prosthesis for any reason. The cause of failure were aseptic loosening (44%), fatigue fracture (16%), local recurrence (14%), infection (13%), and failure of the expansion mechanism (6%). Forty-eight of 64 failed endoprostheses were managed by endoprosthesis reconstruction with most being revised using the same type of prosthesis. Nine of these patients with failed replacements experienced a second failure and four went on to require an amputation. Aseptic loosening and mechanical failure accounted for most of the failures and they were revised successfully. Sixty percent of the infected cases were salvaged satisfactorily by endoprosthetic revision, whereas, 89% of the local recurrences resulted in amputation. Based on endoprosthesis survival the 7 year failure rates were 31% and 34% for primary and revision reconstructions, respectively. The functional results for the patients with endoprosthesis revisions either were better, unchanged, or on average only slightly lower than results of patients with a surviving endoprosthesis. PMID- 9973978 TI - Rotationplasty in skeletally immature patients. Long-term followup results. AB - Twenty-one skeletally immature patients with a Grade IIB osteosarcoma about the knee were treated with a modified Van Nes rotationplasty. Fourteen patients were followed up for 4 to 10.5 years (mean followup, 8 years). Functional assessment using Enneking's method showed all had good or excellent results. No patient thought that the reconstruction affected their ability to achieve recreational, sporting, or career goals. The reconstruction is durable and is not associated with an increase in late complications. PMID- 9973979 TI - Limb salvage and outcome of osteosarcoma. The University of Muenster experience. AB - One hundred thirty-six patients with non-metastatic high grade osteosarcoma treated from 1978 to 1994 in one institution with a multidisciplinary approach that included intravenous neoadjuvant chemotherapy were studied to evaluate which factors influence the outcome of modern orthopaedic therapy. Anatomic location, tumor volume, surgical margins, complications, and functional outcome were analyzed. Seventy-nine patients had a limb salvage procedure, 21 had a rotationplasty, and 33 had an amputation. Limb salvage consisted of 32 endoprostheses, 39 allograft replacements, six autograft replacements, and two shortening procedures. Three patients died during preoperative chemotherapy treatment. At a mean followup of 43 months, 81 patients continue to be disease free, three are alive after local recurrence, 17 are alive after having metastatic lesions, five are alive with metastatic lesions present, and 30 patients died of their disease. Forty-seven patients had pulmonary metastatic lesions, 14 had osseous metastatic lesions, three had abdominal metastatic lesions, two had lymphatic metastatic lesions, and eight patients had skip metastatic lesions. Prognosis correlated with chemotherapy response, surgical margins, and tumor volume. The minor complication rate for limb salvage was 4% and the major complication rate was 52%. Amputations had a 6% minor complication rate and 34% major complication rate. Rotationplasties had 10% minor and 48% major complication rates. The Musculoskeletal Tumor Society functional evaluation after limb salvage showed that 23 (38%) patients had more than 75% of the maximum functional score, 34 (56%) were from 50% to 75%, and three (5%) less than 50%. Of the rotationplasties, six (67%) were functionally better than 75% and three (33%) were functionally better than from 50% to 75%. In the group of amputations, 13 (56%) were from 50% to 75%, and 10 (44%) less than 50%. The extent of preoperative necrosis, surgical margins, and tumor volume are the most important prognostic factors. The increase in limb salvage procedures and the better long term survival of patients results in a higher rate of immediate and delayed complications. Functional outcome after rotationplasty is superior to limb salvage reconstruction and amputation. PMID- 9973980 TI - Evaluating functional outcome in patients with lower extremity sarcoma. AB - The Short Form 36, The Toronto Extremity Salvage Score, and the 1987 and 1993 Musculoskeletal Tumor Society Rating Scales were compared as measures of functional status for patients with lower extremity sarcoma. The study included 97 patients with lower extremity sarcoma and evaluated each measure on the following measurement properties: conceptual framework; statement of the purpose; feasibility; breadth of content; depth of measurement; cross sectional and longitudinal reliability; and validity and responsiveness. The Short Form 36 represents patients' perceptions of their physical and mental health and is practical to use. However, the validity of the measure is questionable for the patients with sarcoma because the subscale structure could not be reproduced in the current data. The Toronto Extremity Salvage Score meets all standards of measurement with the exception of breadth of content as it measures only physical function. The 1987 and 1993 Musculoskeletal Tumor Society scales do not meet the standards of measurement. In choosing an outcome measure for the extremity sarcoma population, the Toronto Extremity Salvage Score has superior measurement properties when compared with the Short Form 36 or the 1987 and 1993 Musculoskeletal Tumor Society scales. The Toronto Extremity Salvage Score is a reliable and efficient measure for monitoring patients and for use in clinical trials. PMID- 9973981 TI - Biologic attachment of an allograft bone and tendon transplant to a titanium prosthesis. AB - An Achilles tendon allograft with its bony insertion was used to bridge a Titanium implant, containing an endoprosthetic tendon anchor, and the sheep biceps muscle. Twelve sheep were operated on unilaterally and followed up clinically and histologically for 2, 4 (n = 2), 8, and 12 months (n = 4). Full function of the front limb was regained after 8 to 12 weeks. There were no signs of mechanical loosening at all times. The morphologic changes at the bone block and implant fixation site were an initial revascularization of the allograft bone, which was observed at 2 months and enhanced at 4 months but occurred without any evidence of bone remodeling. This was changed in all specimens taken at 8 and 12 months where intensive new bone development, remodeling, and bone ingrowth in the titanium implant was found. Bone mass was shifted significantly to the tendon insertion half of the bone block because of a creeping substitution of the cancellous allograft bone and bone ingrowth to the implant. Overall bone mass slightly decreased with time but resorption of allograft bone outweighed new bone development only at lesser loaded areas. Transplantation of a bone and tendon allograft to an implant resulted in a revitalized, mechanically stable, and biologically anchored compound. PMID- 9973982 TI - Intraepiphyseal resection of the proximal tibia and its impact on lower limb growth. AB - From 1989 through 1996, 10 children affected by high grade bone tumors of the proximal tibia underwent an intraepiphyseal intercalary resection. The residual epiphyseal bone segment measured less than 2 cm in thickness in all cases and reconstruction always was performed using the combination of a vascularized fibular autograft and a massive bone allograft. The proximal epiphyseal osteosynthesis was fixed by small fragment screws. The aim of this study was to report the growth pattern of the residual proximal tibial epiphysis and to evaluate any possible lower limb discrepancy and/or deformity after the end of skeletal maturity. At current followup six patients were available for the final evaluation. Radiographic documentation included computed tomography scan of both knees before surgery, a panoramic radiographic view and a computed tomography scan of both lower limbs after the end of skeletal growth. The length of both femurs and tibias, the size of the tibial plateau and of the opposite distal femur, and any possible deformity of femur or tibia were measured and compared with the preoperative data. No patient had a limb length discrepancy greater than 3.5 cm. In all cases the ipsilateral femur had a valgus deformity of the hip develop. In two patients this deformity was associated with an elongation of the femur, partially compensating for the shortening of the tibia. The tibial plateau close to reconstruction grew less than the contralateral one (range 2%-8%) but maintained its normal relationship with the distal femur. None of these patients reported any restriction in recreational activities. They could walk, run, and jump. Their functional result according the International Society of Limb Salvage functional grading system was satisfactory in all cases. PMID- 9973983 TI - Local and systemic control after ablative and limb sparing surgery in patients with osteosarcoma. AB - Limb salvage surgery in patients with osteosarcoma is reported to cause a higher rate of local recurrences with a poorer chance of survival. It was the aim of the study to analyze differences between ablative and limb sparing surgery in patients with osteosarcoma who are treated with chemotherapy with respect to local and systemic tumor control and to determine independent prognostic factors. One hundred thirty consecutive patients younger than the age of 21 years who were operated on at the authors' institution for osteosarcoma of the extremities were reviewed. Histologic evaluations of surgical margins according to Enneking and coworkers revealed mostly wide (n = 109) and radical (n = 10) resection margins. The 5-year disease free survival rate was 60% for those patients treated by amputation and 71% for those treated by limb salvage. The overall local recurrence rate was 2.3%; 4.3% for ablation but only 1.2% for limb sparing surgeries. Multivariate analysis showed an independent effect of tumor volume, response to chemotherapy, and as expected, metastases at the time of diagnosis on overall survival. These data indicate that in patients where wide or radical tumor resection can be achieved, no difference in the outcome between ablative and limb sparing surgery occurred in local and systemic tumor control. PMID- 9973985 TI - Functioning muscle transplantation after wide excision of sarcomas in the extremity. AB - Free functioning muscle transplantation was performed after resection of 23 sarcomas in the extremity. There were 21 soft tissue sarcomas and two malignant bone tumors. The tumor resection was performed with a wide margin in all except two patients who had a marginal margin in a limited area. The consequent extensive soft tissue defect received free musculocutaneous flaps, the motor nerve of which was repaired in the recipient site. The most frequent procedure was latissimus dorsi transplantation to replace thigh muscles in 17 cases. The other donors included gracilis, tensor fascia lata, and rectus femoris, which were selected according to the site of defects. Patients were followed up for a mean of 60 months (range, 13-119 months). The grafted muscles showed reinnervation at a mean of 6 months postoperatively in all patients except for a 75-year-old patient. Obtained contraction of the muscles was powerful in 18 patients and fair in four patients. Performance of the salvaged limb significantly improved after recovery of the muscles. Although there were five distant recurrences, local recurrence was seen in one patient with systemic metastases. Because muscle loss could be compensated functionally for by the innervated free muscle transfer, the method encouraged surgeons to perform more radical tumor excisions and this may have contributed to the excellent local tumor control that was achieved. Thus, functioning muscle transplantation was extremely useful in limb salvage surgery from the functional and oncologic viewpoints. PMID- 9973984 TI - Failures after operation for skeletal metastatic lesions of long bones. AB - This study was based on 192 patients treated surgically for 228 metastatic lesions of the long bones from 1986 through 1995. The survival rate was 0.3 at 1 year after surgery. The surgical treatment consisted of resection and reconstruction of the involved bone (18), intralesional curettage (133), or stabilization only (77). Reconstruction was achieved by an endoprosthesis in 54 cases, by an osteosynthetic device in 162, by cement only in 10. In two cases no reconstruction was performed. The local failure rate was 11% and the median time to failure was 8 months. Local failure was most frequent in patients with kidney cancer (24%) and in diaphyseal and distal femoral lesions (20%). Among 162 operations involving osteosynthetic devices, 22 (14%) were failures as compared with one of 54 (2%) endoprostheses. Sixty percent of the patients received preoperative or postoperative radiotherapy. Five of the six patients who had surgery for local tumor progression had not received radiotherapy. Eight of 10 nonunions and all five patients who developed a stress fracture had been treated with radiotherapy. It is concluded that endoprosthetic reconstructions are preferable to osteosynthetic devices. The skeletal complications associated with radiotherapy may be circumvented by the use of endoprostheses. PMID- 9973986 TI - Prognosis of early stage avascular necrosis of the femoral head. AB - Seventy-two femoral heads in 63 patients in whom avascular necrosis of the femoral head was in the early stage were followed up prospectively for a mean period of 6 years 1 month. All of the necrotic lesions were confirmed by magnetic resonance imaging. At the time of final outcome, 46 (64%) of the 72 hips were symptomatic. Necrotic lesions greater than 2/3 of the weightbearing portion on T1 weighted central coronal images indicated a high risk of clinical deterioration. Fifty-nine of the 72 hips initially had necrotic lesions greater than 2/3 of the weightbearing portion, and 44 (75%) of these 59 hips were symptomatic at the final outcome. However, in the radiographic assessment of 15 (25%) asymptomatic hips, even when the necrotic lesions were greater than 2/3 of the weightbearing portion as shown by magnetic resonance imaging, the continuous absence of any radiographic abnormality indicated the possibility of a continuous asymptomatic stage for at least several years. PMID- 9973987 TI - Borderline necrosis of the femoral head. AB - To determine whether the histologic lesions classified by the system of Arlet et al as Type 2 (granular necrosis of fatty marrow) and Type 3 (complete medullary and trabecular necrosis) always progress to Type 4 (complete necrosis with marginal medullary fibrosis and appositional new bone formation), 10 femoral heads (nine patients) were monitored for 4 years using serial magnetic resonance images. These femoral heads had been diagnosed histologically as having either Type 2 (seven hips) or Type 3 (three hips) necrosis on initial core biopsies. On the initial magnetic resonance image, none of the femoral heads showed any focal lesions indicative of osteonecrosis. In all instances, superselective angiography showed interruption of the superior retinacular artery, and the bone marrow pressure was elevated. During a followup period of 48 to 54 months, no patient had a reactive low signal intensity band develop on T1 weightings, as evidence of a reparative process around the necrotic portion of the lesion, or any other findings of osteonecrosis on magnetic resonance images. These findings suggest that some Type 2 and 3 lesions of Arlet et al may not develop an obvious reactive interface of reparative revascularization and thus may not progress to definite and classic Type 4 osteonecrosis. This study supports the hypothesis that there is an ischemic threshold between reversible intraosseous hypoxia (bone marrow edema syndrome) and irreversible intraosseous anoxia (classic bone infarction or osteonecrosis) and suggests that borderline necrosis occurs in the transition zone of this ischemic threshold and is nonprogressive. PMID- 9973988 TI - Dislocation after total hip arthroplasty using the anterolateral abductor split approach. AB - The three basic surgical approaches used most commonly in total hip arthroplasty are transtrochanteric, posterior, and anterolateral. Complications related to each of these surgical approaches have been reported including dislocation, trochanteric nonunion, heterotopic ossification, neurovascular damage, postoperative limp, and implant malalignment. The anterolateral abductor split approach previously has been reported to allow ease of access into the hip joint, optimum joint visualization, protection of neurovascular structures of the hip, and predictable results for postoperative hip function restoration. Reviewing a large consecutive series of primary total hip arthroplasty cases (1518), the authors report an overall dislocation rate less than 1% (12:1518; 0.79%). Stratified by preoperative diagnosis, patients undergoing total hip arthroplasty after trauma, or presenting with congenital dysplastic hip are at the highest risk for postoperative dislocation. Primary total hip arthroplasty using the anterolateral, abductor split approach can minimize the rate of postoperative dislocation in the prevailing preoperative diagnostic categories. PMID- 9973989 TI - Metal release and excretion from cementless titanium alloy total knee replacements. AB - Concentrations of titanium, aluminum, and vanadium were measured in the serum and urine of patients with titanium alloy cementless primary total knee arthroplasty components. Patients were categorized in one of five groups. In Group 1, the patellar and tibial articulating surfaces were made of carbon fiber reinforced ultrahigh molecular weight polyethylene. In Group 2, the patellar and tibial surfaces were made of ultrahigh molecular weight polyethylene. In Group 3, the femoral titanium alloy articulating surface was nitrogen ion implanted with ultrahigh molecular weight polyethylene patellar and tibial articulating surfaces. Patients in Group 4 had failed patellar components, and Group 5 was comprised of age and gender matched control subjects without implants. Serum concentrations of titanium were approximately 50 times greater in patients with failed patellar components (Group 4) and approximately 10 times greater in patients with carbon fiber reinforced polyethylene bearing surfaces (Group 1) when compared with Groups 2 and 3 and the control subjects (Group 5). For aluminum and vanadium, no detectable differences were observed among any of the groups. In addition, analysis of 24-hour urine samples showed no significant differences in titanium, aluminum, or vanadium concentrations among any of the groups. Elevated serum titanium levels may serve as a marker of patellar component failure or accelerated femoral component wear in total knee replacements with titanium alloy bearings. The toxicologic ramifications of these findings are unknown. PMID- 9973990 TI - Screw home motion after total knee replacement. AB - The objective of this study was to evaluate the effect of muscle force and the posterior cruciate ligament on screw home motion in patients with total knee replacement in a posterior cruciate ligament retaining prosthesis (10 knees) and a posterior cruciate ligament substituting prosthesis (10 knees). Screw home motion was examined with only active extension and with two types of externally loaded active extension (2 kg and body weight). Screw home motion was measured with a 6 degrees of freedom electrogoniometer (instrumented spatial linkage). Retaining the posterior cruciate ligament maintained screw home motion, with and without external load to muscles, whereas substituting the posterior cruciate ligament maintained screw home motion only under the full external load of body weight. This was not seen with a 2-kg external load. As for the normal knee, it appears that screw home motion of a prosthetic knee is influenced, not only by the presence of ligamentous structures, but also by the activity of the muscles. The activity of the muscles may have a much greater effect on screw home motion with currently used prosthetic designs than does the presence of ligamentous structures. PMID- 9973991 TI - Long-term osteoarthritic changes in anterior cruciate ligament reconstructed knees. AB - To consolidate the indications for anterior cruciate ligament reconstruction and clarify the long-term prognosis associated with current surgical and rehabilitation techniques, the incidence of osteoarthritis in arthroscopically anterior cruciate ligament reconstructed knees requires investigation. Seventy two patients with anterior cruciate ligament ruptures who were active in sports requiring sidestepping and pivoting, or who had recurrent episodes of giving way, underwent arthroscopic bone-patellar tendon-bone anterior cruciate ligament reconstruction. These patients were evaluated for meniscal damage and osteoarthritic changes at the time of surgery and followed up for 7 years. Fifty three patients underwent radiographic evaluation at 7 years, which included anteroposterior, lateral, skyline, and 30 degrees posteroanterior weightbearing views. Radiographic evaluation was performed by three independent surgeons and graded as per International Knee Documentation Committee criteria. Results revealed that knees with chronic anterior cruciate ligament deficiency, even those with intact menisci before reconstruction, suffered early osteoarthritic changes. More severe changes were seen with meniscectomy. Acute anterior cruciate ligament reconstruction with meniscal preservation was shown to have the lowest incidence of degenerative change. Controversy exists regarding the timing of anterior cruciate ligament reconstruction. This study supports early reconstruction of anterior cruciate ligament deficient knees before episodes of giving way occur in individuals intent on continuing activities that involve sidestepping and pivoting. PMID- 9973992 TI - 12-year outcome after modified Watson-Jones tenodesis for ankle instability. AB - In a retrospective study, the long term outcome of the modified Watson-Jones tenodesis according to Lemberger and Kramer was determined using a questionnaire, clinical examination, radiographic data, including stress views, measurement of plantar pressure distribution, and peroneal reaction times on a tilt board. Twenty-five male patients (mean age, 34 years) with a mean followup of 12 years from surgery were available for examination. Eighteen patients (72%) were classified clinically as having excellent or good results. The higher presence of osteophytes in the surgically treated ankle in comparison with the opposite side indicated the progression of arthrosis with time, but this finding could not be related to the reconstruction method. Anterior drawer and talar tilt were reduced significantly in comparison with the preoperative stress radiographs. No differences in plantar pressure distribution were seen between the patients' surgically treated and nonsurgically treated feet. The peroneal reaction times of the peroneus brevis and peroneus longus muscles were significantly shorter in the surgically treated foot compared with the opposite side. It was concluded that the modified Watson-Jones tenodesis effectively corrected lateral ankle instability with no clinical deterioration with time and no influence on gait. PMID- 9973993 TI - Bone tumors of the coracoid process of the scapula. AB - Bone tumors of the coracoid process of the scapula are rare, and diagnosis and treatment often are delayed. The records of 18 patients with bone tumors of the coracoid process were reviewed. Histologic types included eight cases of ordinary chondrosarcoma, three cases of dedifferentiated chondrosarcoma, two cases of osteoid osteoma, and one case each of osteosarcoma, plasmacytoma, lymphoma, giant cell tumor, and aneurysmal bone cyst. All 18 patients had shoulder pain, and eight of them had been treated with steroid injections for nonneoplastic conditions. Radiologically, chondrosarcoma did not always show clear cortical destruction, and one giant cell tumor had features mimicking those of chondrosarcoma. Five patients (three with dedifferentiated chondrosarcoma, one with chondrosarcoma, one with plasmacytoma) died of disease. The coracoid process was the site with a markedly high proportion of chondrosarcomas. Bone tumors of the coracoid process may be difficult to detect on plain radiographs. In the patient with persistent shoulder pain unresponsive to the selected treatment, additional imaging studies should be considered to eliminate the possibility of a bone lesion. PMID- 9973994 TI - Sacroiliac joint tuberculosis. Classification and treatment. AB - The authors treated 16 patients with tuberculosis of the sacroiliac joint. Twelve were treated surgically and four were treated conservatively. The clinical symptoms were buttock and low back pain in all patients, and most had difficulty walking (68.6%) and had radicular pain in their lower limbs (50%). Of the 16 patients, four (15%) had associated tuberculous spondylitis, six (37.5%) had an abscess in the gluteal region, and two (12.5%) had an abscess in the inguinal region. The diagnosis was proven by pathologic specimen in 12 patients and by clinical symptoms, laboratory data, and radiologic findings in the remaining four patients. The authors classified tuberculous sacroiliitis into four types based on the clinical and radiologic findings. Types 1 and 2 were treated conservatively with chemotherapy alone, whereas Types 3 and 4 were treated with surgery and chemotherapy. Healing occurred and was evident in patients who had curettage and arthrodesis (Types 3 and 4) at a mean of 20.8 months, which was comparable with healing in the patients who had chemotherapy alone that occurred at a mean of 23.5 months (Types 1 and 2). The authors suggest that the new classification will be helpful in determining the therapeutic plan of tuberculous sacroiliitis. PMID- 9973995 TI - Analysis of prosthetic femoral heads retrieved at autopsy. AB - This study examined 24 prosthetic femoral heads retrieved at autopsy from patients with clinically and radiographically successful arthroplasties. Four alumina ceramic and 20 cobalt chrome heads in service for an average of 8.5 years were examined with a contact and a laser stylus profilometer. The authors documented general increases in surface roughness of the cobalt chrome and ceramic femoral heads attributable to in vivo articulation and also observed wear polishing around the apical region of the cobalt chrome heads. The roughness of the prosthetic femoral heads was compared with the polyethylene wear in the matching liners. No relationship was found between femoral head roughness values and polyethylene wear or component duration in situ. The only variable related to the pattern of head roughness and polyethylene wear was the presence of embedded particle debris in the polyethylene liner. Roughness parameters for cobalt chrome heads without embedded debris in the polyethylene liner were fairly uniform around the head. Roughness values, which were higher for heads associated with debris, had a decreasing gradient of surface roughness from the equator to the apex. In addition, the polyethylene wear rate for cups with embedded particle debris in the liner was significantly greater than the wear rate for cups without embedded debris. This study also showed a strong correlation between surface roughness values measured with the contact profilometer and values measured with the noncontact laser profilometer. However, laser profilometer values were four to six times higher, indicating that roughness parameters measured by the two different profilometers cannot be compared directly. Findings of this study point consistently to the influence of third body wear particles on prosthetic femoral head roughness and polyethylene wear. These results stress the importance of minimizing all foreign body debris in maintaining a well functioning articular couple. PMID- 9973996 TI - Marrow cell culture on poly-L-lactic acid fabrics. AB - Bone marrow cells from rat femurs were cultured in Eagle Minimum Essential Medium containing 15% fetal calf serum until confluence. After the cells were trypsinized, they were subcultured on fabrics made of biodegradable poly-L-lactic acid for 2 weeks in the medium containing fetal calf serum, ascorbic acid phosphate, beta-glycerophosphate, and with and without dexamethasone. In the presence of dexamethasone, the fabrics showed many mineralized nodules together with cuboidal shaped cells that had osteoblastic activity, as evidenced by high alkaline phosphatase activity and the appearance of osteocalcin messenger ribonucleic acid. However, in the absence of dexamethasone, nodules did not form and many fibroblastic cells appeared with no evidence of osteoblastic activity. These results indicate the possibility of making a hybrid ligament substitute having an in vitro prefabricated bone anchor. PMID- 9973997 TI - Rigid or sliding plate. A mechanical evaluation of osteotomy fixation in sheep. AB - Fracture fixation using rigid plates leads to direct bone union, but it also may lead to complications because of stress protection osteopenia. This study aims to compare the mechanical characteristics restored during the callus formation after an osteotomy is fixed with two types of internal plate fixation. Twenty-four adult female sheep were divided randomly into three groups of eight each, which were euthanized at 2, 4, and 6 months after operation. Half of them had their osteotomized radius fixed with a seven hole dynamic compression plate, whereas in the remainder a sliding plate was used. The sliding plate consists of two halves connected together in such a way as to permit axial sliding of the one within the other, thus allowing cyclic axial load transfer at the fracture site. Bone strips obtained from the healthy (control) and the surgically treated side were subjected to four-point bending tests. The effective modulus of elasticity, ultimate bending strength, and energy absorption to fracture (toughness) were calculated. All parameters were restored more quickly in the sliding plate group, but there was no statistically significant difference observed at 6 months when all the osteotomies were united completely. Thus, the sliding plate, by allowing axial loading at the fracture site, led to a faster callus maturation and hence bony union, which, hopefully, will permit earlier full weightbearing and functional recovery of the injured limb. PMID- 9973998 TI - A 90-year-old woman presenting with hip pain. PMID- 9973999 TI - The next 10 years--the bone and joint decade. PMID- 9974000 TI - [Clinical studies of patients with spinal cord metastases]. AB - Eighty-one patients with spinal-cord tumors are hospitalized in the Clinic of Emergency Neurology and Neurosurgery over the period 1988 through 1997. Of the total number, 74 patients of which 25 presenting metastases from neoplasms with primary location out of the central nervous system, are subjected to operation. There are 4 tumors involving the cervical segment, 1--cervicothoracic, 17- thoracic, 1--thoracolumbar, and 2--lumbar segment. Histological verification is done in all patients operated on. The indications for undertaking surgery in this particular contingent of patients are discussed. PMID- 9974001 TI - [Pathophysiologically advisable operations on the biliary-hepatic-pancreatic system]. AB - Nowadays, the modern operative treatment of biliary-hepatic-pancreatic diseases is pathogenetically substantiated. In lithiasis and cholecystitis removal of the gallbladder should be undertaken only after assessment of the patency and output of the biliary tree (i.e. from the biliary canal) following visual, instrumental and if necessary--manometric and intraoperative cholangiographic study. To eliminate an obstacle--calculus or postampullar papillitis--it is necessary to perform papillotomy or papilloplasty using a balloon catheter introduced through the choledochus and electric knife if practicable. Since 1970, an operation of the kind is carried out in 79 patients, and with deperitonization (denervation and delymphatization)--in eleven patients presenting cholangiohepatitis and biliopancreatitis. In twelve patients, owing to pathological changes in the preampullar portion of choledochus, choledochoduodenostomy according to a modified technique, type "frog mouth", is done in the distal choledochus with formation of a distal convex flap from the anterior wall of te choledochus with an anti-reflux effect. In pre-combined with postampullar stenosis papillotomy and papilloplasty are performed, and if necessary dilatation or osteowirsungotomy plus drainage. In unobstructued cholangiohepatitis and biliopancreatitis, it is sufficient to supplement cholecystectomy with Kehr drainage. The ideal echinococcotomy is done according to a personal modification through hydraulic stratification of the fibrous capsule (1958). Segmental resection is necessitated in marginal, petrified and suppurated cysts in 28 patients, and lobectomy--in two. Resections are performed by hydraulic and instrumental division and hemostasis along the lines of anatomical separation or in the pericyst space. PMID- 9974002 TI - [The significance of congenital inhibitor deficiency in acute pancreatitis]. AB - In the past few years, genotype influence on the occurrence and developmental course of acute pancreatitis is ever more frequently accounted for. Forty-three patients presenting mild (2), medium-severe (33) and severe (6) form of the disease are covered by the study, undertaken with the purpose to assay the role played by some immunoglobulins and polymorphic plasma proteins in this particular disease. In evaluating plasma proteins a deficit of the protease inhibitor Alpha1 antitrypsin is found in twelve patients. However in two cases only Alpha1 antitrypsin deficit is associated with deficiency of the other protease inhibitor -the Alpha2 macroglobulin. In acute pancreatitis patients a genetically determined deficit of protease inhibitory activity is documented, considered a good reason to undertake conservative management using protease inhibitors in the initial phases of the condition. PMID- 9974003 TI - [Immune deficiency in the genesis of acute postoperative pancreatitis (initial studies)]. AB - The issue of acute postoperative pancreatitis (APP) development is discussed against the background of the immune state of the organism. The problem in itself is by no means a new one. Attention is called to the major role of immunodeficiency as an underlying cause of APP. Proceeding from experience had with two observations, the early results of researches along this line are presented. PMID- 9974004 TI - [A clinico-morphological parallel in peptic ulcer in middle and old age]. AB - Based of clinical and obduction case material covering the period 1990-1997, the clinical profile, morphological patterns and therapeutic approach, consistent with the specificity of age, complications of the basic disease and presence of concomitant diseases, are summed up. The results of biopsy and necropsy studies, following statistical processing by the methods of variation and correlation analysis, afford information on the morbidity in either gender, as well as on the location and morphological patterns of ulcers, their complications and associated diseases. Over the period 1990 through 1997, a total of 5425 cases are subjected to obduction study. Of them 799 (14.7 per cent) are with ulcers, 543 men and 256 women at 2.1-to-1 male-to-female ratio. Four-hundred fifty-nine (54.4 per cent) are in advanced and old age, at male-to-female ratio 1.9-to-1. There are 362 gastric ulcer patients (45 per cent), 237 men and 125 women, at male-to-female ratio 1.8-to-1. Of the latter 176 (48.6 per cent) are in advanced and old age, 94 men and 82 women at approximative male-to-female ratio 1-to-1. PMID- 9974005 TI - [The organ-conserving treatment of early carcinoma of the breast. I. The biological, histological and radiobiological bases. II. Radiotherapy--an essential component in the organ-conserving surgery of early carcinoma of the breast]. AB - One of the major achievements in the last 20 years is the awareness that mutilating surgery--mastectomy--is a biologically obsolete therapeutic approach, and no longer indicated in the treatment of early breast cancer which in turn, has a dramatic effect insofar as mammary gland preservation is obviously an important consideration for each woman. Either of the operative procedures- quadrantectomy and lumpectomy--should be by all means followed by radiotherapy with a view to control local recurrences of the process. Clinical trials covering borderline disciplines assay the contribution of the answers to a number of questions, as follows: 1) Is the effect of conservative mammary gland treatment comparable to that of mastectomy? 2) Is radiotherapy an essential component of conservative breast surgery? 3) Is conservative surgery indicated in all cases presenting early breast carcinoma? 4) Which are the factors exerting influence on the conservative therapeutic approach to breast cancer? PMID- 9974006 TI - [Relaparotomy in middle-aged and elderly patients with peritonitis following a primary operation for digestive pathology--II]. AB - The study covers 39,233 patients presenting biliodigestive pathology of which 12,230 in advanced and senile age, admitted to the emergency surgery section of the EMI "NI Pirogov" over a 12-year period (1985 through 1996). Of the total number, 6555 or 53.71 per cent are subjected to operation, with postoperative deaths amounting to 477 (7.27 per cent). In 320 cases (4.88 per cent) 218 men and 102 women, relaparotomy is done for postoperative peritonitis with 55 per cent lethality. Postoperative peritonitis is usually observed after operative treatment of ulcers. Operations for bleeding ulcers are performed in 175 patients of which 32 (18.28 per cent) are relaparotomized. Those operated for postoperative peritonitis are 65 per cent with 21 fatal outcomes; the commonest cause of death is insufficiency of the anastomosis or duodenal stump, followed by subhepatic and interfold abscesses. PMID- 9974007 TI - [Technics for laparoscopic cholecystectomy--their use and results]. AB - In mini-invasive surgery mainly two operative techniques for laparoscopic cholecystectomy are familiar and implemented in practice--"American" and "French" technique. Over the period May 1993 to September 1997, in the two surgical clinics of H. M. I.--Pleven a total of 311 laparoscopic cholecystectomies are performed. Of them 218 are done according to the "American" technique, 87- according to the "French" technique, and six patients are operated using the so called "lifting" technique. In the appear submitted the advantages and shortcomings of the two techniques for laparoscopic cholecystectomy are comparatively studied. The timing of operative intervention CO2 quantity expenditure and intraoperative complications are analyzed. The choice of technique for laparoscopic cholecystectomy depends on the surgeon's personal judgement, but under given situations one of the two techniques or a combination thereof should be mandatorily used. PMID- 9974008 TI - [The use of Diprivan in CO2 laser microlaryngosurgery (MLS)]. AB - It is the aim of the study to outline the advantages of Diprivan anesthesia in laser microlaryngosurgery. The types of endotracheal tubes used in laser MLS are described, with emphasis on their contribution to prevent ignition and fire accidents. The anesthesiological technique employed during surgical interventions is discussed. After comparative assessment with conventional techniques, the inference is reached that Diprivan is a further alternative available, and should be considered in the choice of anesthesiological techniques for MLS. PMID- 9974009 TI - [The use of Diprivan as an anticonvulsant in the early postoperative period of an otogenic brain abscess]. AB - This is a report on a female patient with otogenic cerebellar abscess and symptomatic generalized convulsions, irresponsive to conventional diazepam and phenobarbital therapy. Fractionated propofol administration yields good effect without noteworthy changes in respiration and circulation. PMID- 9974010 TI - [Minicholecystectomy--the technical aspects]. AB - In current interventional medicine operations on the gallbladder and biliary tracts, performed by "mini" access are ever more widely used in practice. Cholecystectomy done through minilaparotomy is an attractive procedure with well established superiorities, irrespective of the enthusiasm for laparoscopic accomplishment of the interventions in this particular field of surgery. Approbation of the method initiates in the early 80-ies, and ever since then it marks a ceaseless improvement in technical respect. In this report reference is made to a number of technical hints, rendering the procedure safer and readily accessible in the routine surgical practice, as well as successfully competing with laparoscopic cholecystectomy. PMID- 9974011 TI - [Sphincter-preserving operations in the treatment of carcinoma of the middle and lower third of the rectum]. AB - The prerequisites for sphincter-salvaging interventions in the operative management of carcinoma of the middle and lower third of rectum are analyzed. Reference is made to 96 scientific publications of the issue, with due consideration given to the anatomical and physiological prerequisites for coloanal anastomoses. Updated knowledge of intramural diffusion of the neoplastic process in distal direction promotes the performing of ablastic surgical intervention with resection line 2 cm beneath the tumor. The practical implications of total mesorectal excision for reducing local recurrences are underscored. Analysis of the summed up literature data warrant the assumption that in the event of differentiated carcinoma of the rectum, located 1.5-2 cm above linea dentata, sphincter-salvaging operation should be undertaken with a priority given to direct manual coloanal, transanal anastomosis. This type of surgical interventions are attractive on account of the likelihood to preserve the anal sphincter complex--a fact having an essential practical bearing on the lifestyle of patients. Eventual local relapses lend themselves readily to diagnosis and treatment by abdominoperineal extirpation. Thus the latter may be deferred in time, and in most patients it may prove unnecessary altogether. PMID- 9974012 TI - [Acute surgical abdomen in middle and old age]. AB - Proceeding from a comprehensive literature survey the urgency of acute abdomen conditions in elderly and senile patients is thoroughly discussed. Not infrequently, geriatric surgeons face serious difficulties of diagnostic and therapeutic character relating to the severity of clinical picture and elevated postoperative lethality, explaining in turn the great surge of interest in the problem. Recent achievements along this line, surgery in particular, provide for adequate conditions for performing early surgical interventions with reduced intraoperative risk in elderly and old age patients presenting acute abdomen. PMID- 9974013 TI - [Colitis cystica profunda--apropos a case]. PMID- 9974014 TI - [Invasive thymoma growing into the pericardium, lung and pleura--the importance of thymectomy with resection and reconstruction of the adjacent structures]. PMID- 9974015 TI - [A giant retroperitoneal cyst deriving from the vestiges of a mullerian duct]. PMID- 9974016 TI - [Bilateral tubo-ovarian actinomycosis and rheumatoid arthritis]. PMID- 9974017 TI - [A one-stage combined approach to tumors in the anterobasal portions of the third ventricle]. AB - Regardless of the current progress in microneurosurgery, the operative management of tumors in the third ventricle is associated with a number of difficulties, and poses a serious challenge to surgeons. A numerous group of neoplasms with the aforementioned location are characterized by developmental course with secondary involvement of the III ventricle. Usually, it is a matter of tumors with suprasellar evolution (craniopharyngiomas, hypophyseal adenomas etc), penetrating through lamina terminalis and growing within the cavity of the ventricle. Radical removal of some of these tumors requires a many-staged approach--basal and transventricular--undertaken at different periods of time. The analysis covers five patients presenting tumors of the III ventricle--4 craniopharyngiomas and 1 dermoid cyst--where single stage basal (across lamina terminalis) and direct (transcallosal or across the lateral ventricle) access to the third ventricle is gained. The situations where such an approach is practicable, the peculiarities of the surgical technique, and the treatment results are discussed. PMID- 9974018 TI - [Atraumatic procedures in common abdominal operations]. AB - The surgical tactics and technical improvements are discussed against the background of personal experience with some common abdominal operations, among which the appendectomy variant leaving the cecum intra-abdominally and using chain retrograde ligature in some cases, with choice of access according to the requirements of the individual case. Special attention is called to retrocecal extraperitoneal complications and Meckel's diverticulum--clinical picture and operative tactics. Emphasis is laid on the advantages of intestinal anastomoses- latero-lateral variant, termino-terminal technique in colo-colostomy and possibilities of latero-terminal sigmoidorectoanastomosis. PMID- 9974019 TI - [Intra-arterial therapy as a treatment method in acute pancreatitis]. AB - Intra-arterial therapy has a definite place in the complex management of pancreatitis. Drug infusion into the celiac trunk and a. mesenterica superior is a procedure bringing about the highest concentration (16-18 times) in the pathological focus (Briskinikol), inactivation of vasoactive and toxic products, interference with autolysis of the gland, allowing in turn the administration of smaller drug amounts. Intraarterial therapy (IT) is carried out in 18 patients presenting destructive pancreatitis: total necrosis--2, focal necrosis--8 and hemorrhagic pancreatitis--8, with ages ranging from 25 to 65 years, in a poor general condition. IT is conducted after catheterization of truncus celiacus and celiacography, with infusion effected through single time introduction of 0.5 per cent novocain solution, heparin, kontrikal, Petphtoruracil, antibiotic and atropine. PMID- 9974020 TI - [Decontamination in colorectal surgery]. AB - The results of perioperative decontamination in a series of 136 patients presenting diseases of the colon and rectum are evaluated. Of the total 74 are subjected to operation according to schedule, and 62 are operated on an emergency basis. Perioperatively, metronidazole plus a cephalosporin antibiotic (cephazolin, cephalothin or cephamandol) are administered. Primary anastomoses are done in 32 cases operated according to schedule, and in fourteen patients operated in the emergency room. Insufficiency of the anastomosis is recorded in 3.5 per cent in the former group, and in 15 per cent in the latter group (p > 0.05). Operative wound suppuration occurs in 5.4 per cent against 13 per cent (p > 0.05), with lethality amounting to 1.3 per cent and 19 per cent, respectively (p < 0.001). Postoperative pneumonia is registered in 4 per cent of those operated on schedule and in 9.6 per cent of those operated by urgency (p > 0.05). In either group there is not a single case of operative wound dehiscence. In colorectal operations antibacterial prophylaxis applied perioperatively proves effective in combating systemic and local inflammatory complications. PMID- 9974021 TI - [Hemorrhages from the gastrointestinal tract in middle-aged and elderly patients- the diagnostic-treatment procedures and mortality dynamics]. AB - Hemorrhages from the upper part of the gastrointestinal tract pose serious surgical problems because of their rather elevated incidence, diverse etiopathogenesis, difficulties in diagnostic and therapeutic approach, and last but not least, owing to the high mortality rate. The incidence of patients with ulcers amount to 420 per 100,000 population, with those in advanced and old-age accounting for 15-40 per cent of the total number of affections. In this contingent ulcers run a course associated with a number of peculiarities conditioned by severe lesions, caused by an acute and prolonged blood loss, not infrequently associated with a serious co-morbidity typical of this age. For this reason periodic analysis of lethality due to hemorrhages in the upper segments of the gastrointestinal tract contribute greatly: to evaluate the factors affecting thanatogenesis of this particular disease. establish the dynamic pattern of mortality, and specify the therapeutic tactics influencing such dynamics. PMID- 9974022 TI - [Intraoperative echography in the diagnosis and treatment of minor intraparenchymal cysts in multiple hepatic echinococcosis--a report on 3 cases]. AB - Personal experience with the treatment of minor intraparenchymally located cysts, arising from multiple liver echinococcus is described. The practicability of a different intraoperative technique is discussed. Emphasis is laid on the positive results of application of puncture-aspiration method with ensuing sclerosis, carried out under intraoperative echographic monitoring. PMID- 9974023 TI - [The surgical treatment of perforated gastric and duodenal ulcers in middle-aged and elderly patients--an analysis of the 1985-1996 period]. AB - The problem relating to perforated gastric and duodenal ulcers (PGDU) treatment is still pressing nowadays not only on account of the constant mortality rate (6.7-14.55 per cent according to personal data), but also on account of the lack of universally accepted tenets for their management, irrespective of the fact that the first operative interventions were done more than 100 years earlier, and so far, more than 50 palliative and radical procedures have been suggested. Between 20 and 40 per cent of all ulcer patients are individuals in advanced and senile age. In this contingent a characteristic feature is the elevated incidence of complications, one of them being perforation, necessitating operative treatment and exposing elderly patients to serious surgical and anesthesiological hazards. PMID- 9974024 TI - [Continuous thoracic epidural anesthesia in abdominal surgery]. AB - General anesthesia, applied under emergency conditions in both geriatric patients and patients presenting considerable in severity concomitant diseases (pulmonary and cardiovascular), is associated with serious risks in terms of restoring adequate consciousness, effective spontaneous respiration and pulmonary drainage, not infrequently requiring continuous mechanical ventilation of the patients. A procedure alternative to general anesthesia in abdominal surgery is described, consisting in the application of continuous thoracic epidural anesthesia (CTEDA), reaching i.v. thoracic segment, providing for analgesia of the whole abdomen and myorelaxation promoting accomplishment of the operative intervention against the background of preserved consciousness and spontaneous respiration. This is a report on 70 patients operated under CTEDA in the clinic of emergency surgery, University Hospital "Queen Giovanna"--Sofia, in the period June 1994 through April 1998. The methodology, superiorities and general organic effects of this particular type of anesthesia are comprehensively discussed. Emphasis is laid on the important role played by CTEDA in postoperative analgesia of patients in intensive care units, and on the contribution of the method to exclude any opiates, till recently considered as the most effective for pain relief in the post-operative period. PMID- 9974026 TI - [Secondary sclerosing cholangitis after echinococcectomy]. AB - This is case report concerning secondary caustic sclerosing cholangitis following scolecide with concentrated sodium chloride solution (30%) during operation on a liver echinococcus cyst with involvement of the extrahepatic biliary apparatus only. Hepatojejunostomy is performed. Histological study of the liver demonstrates evidence of severe cholangitis, purulent cholangiolitis and suspected secondary biliary cirrhosis. In conclusion, it is stressed that dynamic postoperative follow-up of patients is mandatory to make early diagnosis of the complication and undertake operative treatment anticipating the development of a cirrhotic process. The search for new, effective scolicides, not damaging the biliary apparatus and hepatic parenchyma, is strongly recommended. PMID- 9974025 TI - [The use of ketamine in an experimental model of generalized cerebral ischemia]. AB - Thus far, a sufficiently effective cerebroprotective substances has not been discovered. Glutamate overproduction plays a key role in ischemic brain lesion. Ketamine is assigned to the group of commonly used clinical anesthetics, being also familiar as NMDA antagonist. Sodium fluoride-induced cerebral ischemia in mice is used as a model of circulatory ischemic lesion. As shown by the experimental data, simultaneous administration of NaF + ketamine has no effect whatsoever on the survivorship of animals, as compared to that in the control group treated with NaF alone. Beforehand treatment of mice with 150 mg/kg ketamine brings about considerable prolongation of the survival term (15 per cent of the animals survive for more than 2 hours). The inference is reached that ketamine is endowed with cerebroprotective activity largely attributable to glutamate antagonism at the level of ischemia involved neurons. PMID- 9974028 TI - [Relaparotomy after an appendectomy]. AB - The analysis covers 2555 appendectomies, performed on an emergency and scheduled surgery basis in the clinic of emergency surgery.--State University Hospital "Queen Giovanna", Sofia, over the period 1985-1997. Relaparotomy is necessitated in 28 cases (1.09 per cent) because of various postoperative complications. Data are presented on the number of relaparotomies, done under conditions of emergency and scheduled surgery, and with a special reference to the pathoanatomical character of appendicitis. The underlying causes of undertaking relaparotomy and postoperative lethality are analyzed. As shown by the obtained results post relaparotomy mortality rate is the highest after primary operation for destructive form of appendicitis and advanced form of peritonitis. PMID- 9974027 TI - [The pre- and postoperative monitoring of the immunological indices and tumor markers in colorectal carcinoma]. AB - The onset of immunological reaction against colorectal carcinoma is based on superficial changes in the malignant cell components following the formation of antigen structures. This explains the interest in the issue and defines the aim of the study. Over a 5-year period, in the Emergency Surgery Clinic, 86 patients with histologically diagnosed colorectal carcinoma (46 men and 40 women) are examined prior to surgery, and 107 patients (55 men and 52 women)--after the operation. The tumor markers CEA, CA 19-9, AFP and immunoglobulin IgA are tested using ELISA and RIA methods. Conventional ultrasound, scintigraphic and CT studies are carried out to detect liver metastases. The obtained results undergo statistical processing with correlation analysis and sensitivity and specificity coefficients. Among those examined preoperatively elevated CEA levels (CEA > 2.5 ng/ml) are recorded in 42 cases (48.9%), and for CA 19-9 (CA 19-9 > 37 E/ml)--in 40 (46.5%). From the patients with complicated colorectal carcinoma in the postoperative period 83 are clinically healthy (77.6%); of the latter marker positive are 16 (19.3%), and marker-negative--67 (80.7%). Relapses and metastases are registered in 24 cases (22.4%) of which marker-positive--19 (79.2%). Liver and abdominal lymph node metastases are detected by US, scintigraphy and CT study. All three imaging methods contribute to diagnose liver metastases in 14 patients (13%). In 32 patients (18 men and 14 women) postsurgical monitoring of immunological IgA levels and tumor markers is done over period ranging from 7-10 days to 2 years postoperatively. Correlative dependences between IgA and CEA (R = +0.99), and between IgA and CA 19-9 (R = +0.97) are also documented. The sensitivity of both markers (CEA and CA 19-9) is low, varying between 38 and 51 per cent, with specificity amounting to 61-67 per cent. The paradoxically high elevation of tumor markers prior to operation shows a constant decrease at 3 months after surgery. CONCLUSIONS: 1. The sensitivity of both markers (CEA and CA 19-9) is low (38-51%), and that is why their use in screening examinations lacks clinical relevance. 2. CEA specificity is by no means high (61-67%), and it may become positive in a number of nononcological diseases (liver cirrhosis and hepatitis, inflammation diseases of GIT and lungs). 3. Plasma CEA and CA 19-9 levels correlate well with the neoplastic process progression/regression. 4. Preoperative CEA level has a prognostic value for postsurgical relapses. 5. High IgA levels are indicators for relapses or metastases from colorectal carcinoma. 6. Tumor histological verification correlates also with the high CEA levels and with the depth of tumor infiltration into the intestinal wall. 7. The dynamic assessment of tumor markers postoperatively has a high informative value in all colorectal carcinoma patients. 8. Pre- and postoperative high CEA levels are observed in patients assigned to the poor prognosis group, and should be given adjuvant therapy. PMID- 9974030 TI - [A rare vascular variation of the upper extremity]. PMID- 9974029 TI - [Resection of the v. portae and its reconstruction with the v. jugularis interna in pancreatic cancer]. PMID- 9974031 TI - [A case of recurrent hepatic echinococcosis with perforation of the cyst into the retroperitoneal space]. PMID- 9974032 TI - [The surgical treatment of extrahepatic bile duct lithiasis]. AB - Data concerning operative treatment of 227 patients with lithiasis of the extrahepatic biliary ducts, covering an eleven-year period (1985 to 1995 inclusive), are presented. In all cases diagnosis and operation are done in the Second Surgical Clinic at the Medical University--State University Hospital "Alexandrovska"--Sofia. By type the surgical interventions are distributed as follows: external drainage of hepaticocholedochus--122 cases (53.74 per cent), choledochoduodenostomy 69 (30.39 per cent) and transduodenal papillosphincterotomy 36 (15.85 per cent). Fifteen patients develop postoperative complications (6.60 per cent), and in five patients the outcome is fatal with postoperative lethality amounting to 2.20 per cent. The basic indications for the various types of surgical interventions are established. PMID- 9974033 TI - [Rare forms of abdominal echinococcosis complicated by rupture]. AB - This is a report on a series of twelve patients presenting ruptured echinococcus in the abdominal cavity, hollow abdominal organ and retroperitoneal space, observed in the period 1985 to 1997. The diagnostic and therapeutic problems faced are discussed with a special reference to the necessity of giving due consideration to these comparatively rare, but by no means less precarious complications in the clinical course of hydatid disease, particularly in endemic regions, such as Bulgaria. PMID- 9974034 TI - [The role of the surgeon in treating multiple organ failure]. AB - Over the period 1990 through 1995, thirty-five patients with multiorgan insufficiency (MOI) undergo treatment. Abdominal operations are performed in all of them, except for one male patient aged 31 years, dying of bilateral pneumonia and metabolic disorders resulting from duodenal stenosis. Overall mortality rate amounts to 77 per cent (20 cases). Programmed peritoneal lavage (PPL) is done in seventeen patients with lethality 77 per cent (13 cases). In two instances iatrogenic damage to the spleen contribute to fatal septic complications development. All PPL treated patients with fatal outcome have bilateral pneumonia. MOI prevention is still closely linked to prophylaxis against the complications producing it. Programmed peritoneal lavage in immunocompromised and malnourished patients is a risk factor equally serious as the septic noxa being attacked, and what is more it runs the risk of inflicting additional iatrogenic noxae. General endotracheal anesthesia in PPL is likewise a factor demanding further clarification. PMID- 9974035 TI - [Phyllodes tumors of the breast]. AB - Phyllodes tumors are mixed tumors of the mammary gland. They account for 0.3 to 0.5 per cent of all breast tumors. This is a report on nineteen cases presenting phyllodes tumors. Depending on the number of mitoses, growth pattern and atypism degree, the neoplasms are classified as benign (12 cases), borderline (2) and malignant (5). Fourteen of them (9 with benign and 5 with malignant phyllodes tumors) undergo clinical follow-up study. A case with bilateral location of the neoplasm exhibiting strongly expressed susceptibility to relapse is described. The basic methods of preoperative diagnosis and the operative treatment procedures used are outlined. PMID- 9974036 TI - [An analysis of postoperative mortality in patients with large-intestine occlusive ileus due to tumor origin]. AB - A total of 232 patients presenting occlusive ileus caused by colorectal carcinoma undergo operative treatment in the period 1979 through 1990. In 160 of them the tumor is located in the colon, and in seventy-two--in the rectum. One-hundred twenty-two radical and 110 palliative operations are performed (52.58 and 47.42 per cent, respectively). Postoperative lethality amounts to 24.57 per cent, with underlying causes peritonitis (35.08%) and severe ileus intoxication (21.05%). The causes of postoperative lethality are analyzed with a special reference to tumor location, extensiveness of the surgical intervention, clinical course of the disease, concurrent complications and concomitant diseases. The lowest is the mortality rate following radical two-stage operations with removal of the neoplasm in the first stage. PMID- 9974037 TI - [Laparoscopy and laparoscopic echography in the diagnosis of pancreatic diseases]. AB - The potentials of laparoscopy (LS) and laparoscopic ultrasonography (LUS) in diagnosing pancreatic diseases are assayed. The study covers forty-five patients of which 36 presenting carcinoma of the pancreas, and nine-acute peritonitis. APUD (VIP) is documented in one case. For the purpose laparoscope R. Wolf and 7.5 MHz echolaparoscopic linear probe obtained from the Aloka company are employed. The LUS technique used in pancreatic diseases is described in details. In the group of pancreatic carcinoma patients 72.2 per cent prove to be inoperable. Emphasis is laid on the superiorities of LUS over transabdominal echography and laparoscopy in diagnosing, staging and resectability evaluation of pancreatic carcinomas, as well as in terms of establishing the indications and practicability of the procedure in acute pancreatitis. LS and LUS are the only preoperative alternative to intraoperative echography, since imaging, endoscopic and histomorphological diagnostic methods are combined. LS in conjunction with LUS are no longer considered as a synonym of peritoneoscopy which in turn, considerably augments the possibilities of the method in handling diseases of the pancreas. PMID- 9974038 TI - [Hemodynamic changes and nitric oxide production in an experimental model of sepsis]. AB - Nitric [correction of Nitrous] oxide is most likely a queer "end mediator" giving rise to vasoplegia in septic shock patients. The study is aimed at comparative assessment of kinetic changes in the synthesis of nitric [correction of nitrous] oxide in experimentally induced sepsis model with the corresponding hemodynamic parameters. The laboratory animals--pigs--are divided up in two groups, and exposed to general narcosis induction, orotracheal intubation and mechanical ventilation under controlled regimen. The hemodynamic parameters studied include: MAP, CO and SVR. Additional endotoxin (1 mg/50 ml) in the form of infusion is given to the animals in the sepsis group. Nitrate production mirrors NO synthesis, insofar as there are no other relevant mechanisms of nitrate synthesis. The kinetic parameters of nitrate production are estimated using stable nitrate isotopes--N15. The theory of compartment models and appropriate computerized simulation are used to calculate the respective constants. In the endotoxin treated group (n = 5) a significantly higher level of synthesis of induced NO production is documented--26 +/- 9 mumol/h, as compared to production in the control group--6 +/- 7 mumol/h, as well as a significant increase in cardiac output and systemic vascular resistance reduction. The good correlation between enhanced NO production and hemodynamic response (increase in cardiac output and decrease in systemic vascular resistance) corroborates the validity of the method. PMID- 9974039 TI - [Telepathology or a new form in the diagnostic work on surgical pathology]. PMID- 9974040 TI - [Intensive therapy units--the links in the risk for the development and spread of hospital infections]. AB - An epidemiological study on the wide spreading of nosocomial infections among patients admitted to intensive care units in Bulgaria is carried out, covering the period 1982 through 1996. The proportion of nosocomial infections registered in the aforementioned wards accounts for 4.66 +/- 0.33 per cent of the overall in patient infectious pathology. Eight per cent of the patients discharged from intensive care units develop infections originating in hospitals. The predominant nosological entities recorded include pulmonary infections, operative wound suppurations and urinary system infections. More than 15 microorganisms, causing agents of infectious processes, are isolated with E. coli ranking first, followed by Staphylococcus spp., Pseudomonas aeruginosa, etc. The partial registration of nosocomial infection cases in the various intensive care units interferes greatly with the practical implementation of updated and adequate measures for prophylaxis and struggle against the infections. Thus, conditions are created promoting prolongation and rising cost of the inpatient treatment, continuous disability, premature death and reduced efficiency of the medical cares delivered. PMID- 9974041 TI - [Choledochoduodenal anastomosis--pro and contra]. AB - Choledochoduodenostomy (CDS), suggested by T. Roth, and performed for the first time by O. Sprengel (1891), became a definitely affirmed operation after the publications of F. Sasse (1913). From purely anatomical standpoint, CDS contributes to bypass all problems relating to obstruction in the retroduodenal, transpancreatic and intramural segments of the hepatocholedochus with a wide orifice for spontaneous passage of eventual newly formed or residual concrements being secured. The basic indications for performing CDS include: multiple concrements in the extrahepatic biliary ducts, ampullar stenosis, cholangitis, chronic pancreatitis, cyst induced enlargement of choledochus and the like. It is worth noting that in most patients more than a single indication are present. The major shortcomings of the procedure with a reference to the long-term results are attributed to potentialities of cholangitis and cholangiohepatitis development, and "blind sac" formation between the anastomosis and p. Vateri. It is established that all patients with poor post-CDS results have stenosis of the anastomosis, or else, the restoration of papillary patency fails (endoscopically confirmed), i.e. they are most frequently a sequel of technical errors. CDS is a safe, readily performed and effective surgical procedure with few (sporadic) postoperative complications, including patients undergoing long-term follow-up study. PMID- 9974042 TI - [An emergency operation in pulmonary histiocytosis X]. PMID- 9974043 TI - [Gastrectomy in stomach ulcer]. PMID- 9974044 TI - [Acute surgical abdomen in Crohn's disease]. PMID- 9974045 TI - [A rare variant of the a. vertebralis sinistra]. PMID- 9974046 TI - [A rare case of acute cholecystitis combined with a mucocele of the appendix]. PMID- 9974047 TI - The presyringomyelic myelopathic state: a plausible hypothesis. PMID- 9974048 TI - What is the role of MR spectroscopy in the evaluation and treatment of brain neoplasms? PMID- 9974049 TI - The link between diagnosis and therapy. PMID- 9974050 TI - The rapidly expanding role of MR imaging techniques in the endovascular treatment of CNS diseases. PMID- 9974051 TI - The "presyrinx" state: a reversible myelopathic condition that may precede syringomyelia. AB - BACKGROUND AND PURPOSE: Alteration of CSF flow has been proposed to be an important mechanism leading to the development of syringomyelia. We hypothesize that a "presyrinx" condition attributable to a potentially reversible alteration in normal CSF flow exists and that its appearance may be caused by variations in the competence of the central canal of the spinal cord. METHODS: Five patients with clinical evidence of myelopathy, no history of spinal cord trauma, enlargement of the cervical spinal cord with T1 and T2 prolongation but no cavitation, evidence of altered or obstructed CSF flow, and no evidence of intramedullary tumor or a spinal vascular event underwent MR imaging before and after intervention that alleviated obstruction to CSF flow. RESULTS: Preoperatively, all patients had enlarged spinal cords and parenchymal T1 and T2 prolongation without cavitation. Results of MR examinations after intervention showed resolution of cord enlargement and normalization or improvement of cord signal abnormalities. In one patient with severe arachnoid adhesions who initially improved after decompression, late evolution into syringomyelia occurred in association with continued CSF obstruction. CONCLUSION: Nontraumatic obstruction of the CSF pathways in the spine may result in spinal cord parenchymal T2 prolongation that is reversible after restoration of patency of CSF pathways. We refer to this MR appearance as the "presyrinx" state and stress the importance of timely intervention to limit progression to syringomyelia. PMID- 9974052 TI - Is reversible enlargement of the spinal cord a presyrinx state? PMID- 9974053 TI - Percutaneous biopsy of the thoracic and lumbar spine: transpedicular approach under fluoroscopic guidance. AB - Eighteen patients with vertebral lesions located in the thoracic or lumbar spine underwent percutaneous biopsy performed via a transpedicular approach under fluoroscopic guidance. This technique led to an accurate diagnosis in 16 cases (89%). No complications were encountered. For percutaneous lumbar and thoracic vertebral biopsy, the transpedicular approach is a safe and accurate alternative to the posterolateral approach. PMID- 9974054 TI - Lumbar extradural hemangiomas: report of three cases. AB - The CT, MR, and histologic findings of three patients with surgically proved lumbar extradural cavernous and arteriovenous hemangiomas are reported. All three patients suffered from radicular and low back pain that disappeared completely or nearly so after total surgical excision. In each case, neuroimaging studies showed a well-defined ventrally located extradural mass with no bone involvement. On MR images, all lesions were homogeneous and isointense on noncontrast T1 weighted images and hyperintense on T2-weighted images relative to the intervertebral disk. Homogeneous enhancement was seen in one of the two cases in which contrast-enhanced T1-weighted images were obtained. Purely extradural hemangiomas should be included in the differential diagnosis of lumbar extradural soft-tissue lesions. Features that may help to distinguish this entity from the more common extruded disk herniation or neurogenic tumors are its homogeneous high signal intensity on T2-weighted images, ovoid shape, and lack of anatomic relationship with the adjacent intervertebral disk or exiting nerve root. PMID- 9974055 TI - Persistence of the notochordal canal: MR and plain film appearance. AB - We report a case of an unusually prominent persistent notochordal canal involving the T12-L5 vertebrae. This rare anatomic variation was discovered as an incidental finding in a patient with lymphoma undergoing MR imaging for evaluation of back pain. MR images showed a vertically oriented canal contiguous with the intervertebral disks traversing the anterior aspect of each affected vertebral body. Plain films showed a sclerotic rimmed central channel that flared at each vertebral endplate to merge with the disk spaces. PMID- 9974056 TI - Diagnostic and therapeutic consequences of repeat brain imaging and follow-up vascular imaging in stroke patients. AB - BACKGROUND AND PURPOSE: Recently, the diagnostic and therapeutic importance of repeat radiologic imaging in stroke patients has been questioned. The aim of this study was to show the therapeutic and diagnostic consequences of both repeat brain imaging and follow-up vascular imaging in this group of patients. METHODS: Neuroradiologic images and reports as well as clinical records of 317 patients (209 men and 108 women; mean age, 63 years) were reviewed retrospectively to determine the number of modifications made to the diagnosis and therapeutic regimen and to the classification of neuroradiologic findings. RESULTS: Two hundred thirty-eight repeat imaging procedures were performed in 171 patients. Of these, 76 were vascular imaging examinations (11 CT angiograms, 13 MR angiograms, 52 digital subtraction angiograms) and 162 were cross-sectional brain imaging studies (54 MR images, 108 CT scans). Forty of the 76 vascular imaging procedures and 77 of the 162 repeat cross-sectional brain imaging studies led to important diagnostic modifications with consequences for the patients' therapy and prognosis. CONCLUSION: Our study establishes that vascular imaging methods as well as cross-sectional brain imaging used as repeat imaging procedures in stroke patients can have important diagnostic and therapeutic consequences. We believe that repeat imaging in selected subgroups will be cost-effective. PMID- 9974057 TI - Severe occlusive carotid artery disease: hemodynamic assessment by MR perfusion imaging in symptomatic patients. AB - BACKGROUND AND PURPOSE: Cerebral hemodynamic status has been reported to influence the occurrence and outcome of acute stroke. The purpose of this study was to assess hemodynamic compromise in symptomatic patients with severe occlusive disease of the carotid artery by the use of echo-planar perfusion imaging. METHODS: Spin-echo echo-planar perfusion imaging was performed in 11 patients (two had bilateral disease) with severe stenosis or occlusion of the carotid artery who had experienced either a recent transient ischemic attack or minor stroke. Relative cerebral blood volume (rCBV) maps and relative mean transit time (rMTT) maps were generated from the time-concentration curve. Findings on T2-weighted images, angiograms, rCBV maps, and rMTT maps were compared and assessed qualitatively and quantitatively. RESULTS: Although the abnormalities on T2-weighted images were absent, minimal, and/or unrelated to the degree of stenosis or collateral circulation, rMTT maps showed much larger and more distinct perfusion abnormalities along the vascular distribution of the affected vessels in all 13 vascular territories of the 11 patients. Despite obvious abnormalities on rMTT maps, none of the patients had evidence of decreased rCBV in the affected brain tissue (increased in three, normal in eight). A statistically significant difference in rMTT values was found between the affected and unaffected brain tissue, whereas no significant difference was seen in rCBV values. CONCLUSION: Echo-planar perfusion imaging is a noninvasive and rapid method for evaluating the hemodynamics in severe occlusive carotid artery disease and the compensatory vascular changes, and it may be useful in patient management. PMID- 9974058 TI - Ultrafast diffusion-sensitive MR imaging of brain on an open scanner at 0.2 T. AB - We describe new strategies for fast diffusion-sensitive MR imaging of ischemic brain or spinal cord lesions. The methods provide diagnostic image quality in less than 1 s per section and are used in conjunction with low-field-strength open MR scanners. Single-shot sequences combine diffusion-sensitive preparation with a modified fast spin-echo data acquisition. Results are presented from healthy volunteers and from two patients with recent and older ischemic brain lesions. PMID- 9974059 TI - Dynamic CT measurement of cerebral blood flow: a validation study. AB - BACKGROUND AND PURPOSE: Our objective was to develop a method to correct for the effect of partial volume averaging (PVA) in the CT measurement of contrast enhancement in small arteries, and to validate a dynamic contrast-enhanced CT method for the measurement of regional cerebral blood flow (rCBF). METHODS: Contrast-enhanced CT scans of tubes of known inner diameters were obtained to estimate the size-dependent scaling factors (PVSF) due to PVA. The background subtracted image profiles of the contrast-filled tubes were fitted to gaussian curves, and the standard deviations (SDs) of these curves were correlated with the PVSF of each tube. In the second part of this investigation, 13 studies were performed in six New Zealand white rabbits under normal conditions. Dynamic CT measurements of rCBF, regional cerebral blood volume (rCBV), and regional mean transit time (rMTT) were calculated in the left and right parietal lobes and the basal ganglia. The CT rCBF values were compared with those obtained by the microsphere method, which is the standard of reference. RESULTS: We found strong correlations for the SDs of the gaussian curves to the known inner diameters of the tubes and to their size-related PVSF. These correlations demonstrated that the error from PVA in the measurement of arterial enhancement can be corrected without knowledge of the actual size of the artery. The animal studies revealed a mean (+/- SD) rCBF of 73.3 +/- 31.5 mL/100 g per minute, a mean rCBV of 1.93 +/- 0.74 mL/100 g, and a mean rMTT of 1.81 +/- 1.02 seconds. A strong correlation was found between rCBF values derived by the CT and the microsphere methods. CONCLUSION: We have validated a new dynamic CT method for measuring rCBF. The accuracy of this technique suggests that it can be used as an alternative diagnostic tool to assess the cerebral hemodynamics in experimental and clinical situations. PMID- 9974060 TI - CNS vasculitis in autoimmune disease: MR imaging findings and correlation with angiography. AB - BACKGROUND AND PURPOSE: MR findings in CNS vasculitis and their correlation with angiography have not been clearly defined. We therefore explored three hypotheses regarding CNS vasculitis associated with autoimmune disease: 1) MR imaging is highly sensitive; 2) a typical MR appearance exists; and, 3) MR and angiographic findings correlate well. METHODS: We studied 18 patients with CNS vasculitis associated with autoimmune disease, characterized the MR lesions by type, size, number, and location, and correlated the MR findings with those of angiography. RESULTS: All patients with CNS vasculitis had abnormalities on MR studies. On average, four +/- two lesions per patient were detected on MR images. The lesions were located in the subcortical white matter (n = 20), cortical gray matter (n = 16), deep gray matter (n = 16), deep white matter (n = 9), and cerebellum (n = 9). Only 65% of MR lesions were evident on angiograms; 44% of the lesions revealed on angiograms were detected by MR. CONCLUSION: MR imaging is sensitive for CNS vasculitis. Lesions attributable to CNS vasculitis in autoimmune disease are distributed nearly equally among cortical, subcortical, and deep gray matter structures. The modest correlation between MR imaging and angiography suggests that the two techniques provide different information about CNS vasculitis and that both types of studies are needed for the complete assessment of damage caused by vascular abnormalities. PMID- 9974061 TI - Perfusion and diffusion imaging: a potential tool for improved diagnosis of CNS vasculitis. PMID- 9974062 TI - Characteristic MR lesion pattern and correlation of T1 and T2 lesion volume with neurologic and neuropsychological findings in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). AB - BACKGROUND AND PURPOSE: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an arteriopathy related to a genetic defect of the notch 3 gene on chromosome 19. The purpose of this study was to evaluate lesion distribution and volume using MR imaging and to correlate the lesion volume with the neurologic and neuropsychological findings. METHODS: Twenty members of two families (14 with CADASIL as determined by linkage analysis, six healthy) were studied with MR imaging. Two observers evaluated the MR findings semiquantitatively and quantitatively. MR results were then correlated with neurologic and neuropsychological findings. RESULTS: A typical pattern of lesion distribution in patients with CADASIL was found: the frontal lobe was the site with the highest lesion load, followed by the temporal lobe and the insula. The total lesion volume on T1-weighted MR images correlated significantly with the degree of disability and the degree of impairment in neuropsychological functions (including attention, memory, and conceptual and visuospatial functions). CONCLUSION: In CADASIL patients, a common pattern of cerebral lesion distribution is found. The total T1 lesion volume is an important parameter to correlate with disability, as it may prove to be helpful in predicting the natural history of the disease. PMID- 9974063 TI - Cerebral arteriovenous malformations: diagnostic value of echo-enhanced transcranial Doppler sonography compared with angiography. AB - BACKGROUND AND PURPOSE: The purpose of our study was to examine the clinical value of echo-enhanced transcranial power Doppler sonography (EE-TCD), including it ability to assess hemodynamic parameters of the intracranial vasculature, in patients with suspected cerebral arteriovenous malformations (AVMs) and to compare this method with angiography. METHODS: Sixteen patients with suspected cerebral AVMs were examined with EE-TCD and angiography. As an echo-enhancing agent, SHU 508A (Levovist) was administered intravenously by bolus injection in nine patients and by continuous infusion in seven. Sonograms were reviewed without knowledge of other imaging results and were correlated with angiographic findings. RESULTS: Angiography showed AVMs in 12 of 16 patients. Eleven lesions were located in the anterior or middle fossa and one was in the posterior fossa. EE-TCD was slightly less sensitive in the detection of AVMs (92%, 11/12 lesions), since in one patient the lacking acoustic window did not allow a transcranial examination. EE-TCD slightly underestimated AVM size compared with angiographic findings but showed feeding arteries with sufficient acoustic properties. In seven patients (58%), angiography revealed a coincidental blood supply from another intracranial or extracranial vessel, which was missed by EE-TCD in all cases. Assessment of peak systolic velocities and resistive indexes resulted in a higher (mean, 191.1 cm/s) and a lower (mean, 45.7%) value, respectively, in the feeding arteries as compared with the contralateral arteries (mean, 101.8 cm/s and 55.6%, respectively). Side-to-side differences were significantly higher in patients with AVMs than in those without a malformation. Signal enhancement was markedly longer with continuous infusion (mean, 520 seconds +/- 28.2) than with bolus injection (mean, 145 seconds +/- 10.5) of the contrast agent. CONCLUSION: In our limited study group, EE-TCD was a sensitive method for the detection of AVMs, and Levovist proved to be a safe and effective echo-enhancing substance. PMID- 9974064 TI - Follow-up of conservatively managed epidural hematomas: implications for timing of repeat CT. AB - BACKGROUND AND PURPOSE: Small asymptomatic epidural hematomas (EDHs) are frequently managed nonoperatively with good neurologic outcome. Our goals were to determine the frequency and timing of enlargement of acute traumatic EDHs that are not immediately surgically evacuated as well as to identify factors associated with rehemorrhage. METHODS: Of 252 consecutive patients with acute traumatic EDH who were treated over a 5-year period, 160 were managed nonoperatively. Their CT scans, imaging reports, and medical records were reviewed retrospectively. Parameters analyzed as possible predictors of rehemorrhage during nonoperative management were size of the EDH, presence of an associated fracture, contralateral brain injury, midline shift, coagulopathy, and neurologic and physiological injury as measured by the Revised Trauma Score. We compared discharge discharge disposition as a proxy for neurologic condition at discharge. RESULTS: The EDH enlarged in 37 (23%) of the 160 patients during conservative management. Mean enlargement was 7 mm, and the mean time to enlargement was 8 hours after injury and 5.3 hours after CT diagnostics. EDH enlargement occurred within 36 hours after injury in all cases. Of the parameters analyzed, only a high Revised Trauma Score correlated significantly with EDH rehemorrhage, suggesting that intubation and chemical paralysis may prevent rehemorrhage through the restriction of head movement and the control of blood pressure. The subgroup of patients with rehemorrhage experienced no difference in neurologic outcome despite a higher rate of clinical deterioration. CONCLUSION: EDH enlargement occurs frequently, but early. Repeat imaging with CT is most appropriate within 36 hours after injury. PMID- 9974065 TI - Conservative management of epidural hematomas: is it safe and is it cost effective? PMID- 9974066 TI - Classification of biopsy-confirmed brain tumors using single-voxel MR spectroscopy. AB - BACKGROUND AND PURPOSE: Our purpose was to develop a classification scheme and method of presentation of in vivo single-voxel proton spectroscopic data from astrocytomas that most closely match the classification scheme determined from biopsy specimens. Since in vivo proton spectroscopy is noninvasive, it may be an attractive alternative to intracranial biopsy. METHODS: Single-voxel spectra were acquired using the point-resolved spectroscopic pulse sequence as part of the Probe spectroscopy package on a G.E. 1.5-T Signa scanner. Subjects consisted of 27 patients with biopsy-confirmed brain tumors (13 with glioblastoma multiforme, six with anaplastic astrocytoma, and eight with low-grade astrocytoma). The patients were divided into groups based on the histologic subtype of their tumor for different treatment protocols. RESULTS: Metabolic peak areas were normalized for each metabolite (choline, creatine, N-acetylaspartate, lactate) to the area of the unsuppressed water peak and to the area of the creatine peak. Kruskal Wallis nonparametric analysis of variance (ANOVA) tests showed statistically significant differences among the tumor groups for all the area ratios. The lactate/water ratio could be used to distinguished all three tumor groups, whereas the choline/water ratio distinguished low-grade astrocytomas from the two high-grade groups. Both the choline and lactate ratios could be used to separate the high-grade from the low-grade tumors. CONCLUSION: Specific relative metabolic peak area ratios acquired from regions of contrast-enhancing brain tumor can be used to classify astrocytomas as to histopathologic grade. PMID- 9974067 TI - Focal lesion in the splenium of the corpus callosum in epileptic patients: antiepileptic drug toxicity? AB - BACKGROUND AND PURPOSE: Discrete focal lesions in the splenium of the corpus callosum on MR images in epileptic patients have received little attention in the literature. Our purpose was to describe these lesions, which may be related to the toxicity of antiepileptic drugs (AEDs), and to discuss the possible mechanisms of their development. METHODS: We examined six patients with epilepsy whose brain MR imaging findings showed a discrete focal nonhemorrhagic lesion in the splenium of the corpus callosum. The medical records and MR images were reviewed retrospectively with respect to the patients' clinical history, medication, and laboratory findings to determine the etiology of the lesion. RESULTS: In all six patients MR imaging showed a focal lesion in the splenium of the corpus callosum, which was ovoid in shape and 15 to 19 mm in size. In the three patients who received contrast material, there was no enhancement of the lesion. Four of six patients had a history of medication with dilantin, in two of whom the level of serum dilantin was found to be elevated (22.3 micrograms/mL and 70.4 micrograms/mL, respectively). Vigabatrin was administered in three patients, one of whom took dilantin together with vigabatrin. In two patients, the focal lesion in the corpus callosum disappeared on follow-up MR images after withdrawal of dilantin and/or vigabatrin. CONCLUSION: A discrete, focal, ovoid, nonhemorrhagic lesion in the splenium of the corpus callosum may be seen on brain MR images of patients with epilepsy. The lesion is considered to be reversible demyelination related to AEDs toxicity. PMID- 9974068 TI - Interscanner variation in brain MR lesion load measurements in multiple sclerosis using conventional spin-echo, rapid relaxation-enhanced, and fast-FLAIR sequences. AB - BACKGROUND AND PURPOSE: Different MR pulse sequences have been proposed for measuring multiple sclerosis (MS)-related abnormalities. The reproducibility of measured brain MS lesion volumes was compared for MR images performed using different scanners and different pulse sequences. METHODS: Nine patients with relapsing-remitting MS were each imaged on two scanners and, on each occasion, dual-echo conventional spin-echo, dual-echo rapid-acquisition relaxation-enhanced (RARE), and fast fluid-attenuated inversion recovery (fast-FLAIR) images were obtained. The lesion volume present on each image was evaluated three times by a single observer in random order, using a local thresholding technique. RESULTS: The mean lesion volumes present on fast-FLAIR images were significantly higher than those measured on dual-echo conventional spin-echo and RARE images. The mean intraobserver coefficients of variation for the different sequences and scanners ranged from 3.0% to 4.2% (no statistically significant difference). For each of the sequences, the use of different scanners introduced a variability that was higher than the intraobserver variability: the interscanner coefficient of variation was 7.4% for conventional spin-echo, 9.5% for RARE, and 18.5% for fast FLAIR images. CONCLUSION: Our study confirms that the use of different scanners significantly influences lesion loads measured from MR images of patients with MS and establishes that newer sequences are more susceptible to measurement variability. It also indicates that, if newer sequences are to be used in clinical trials, careful standardization is needed. PMID- 9974069 TI - Comparative MR analysis of the entorhinal cortex and hippocampus in diagnosing Alzheimer disease. AB - BACKGROUND AND PURPOSE: Our purpose was to use volumetric MR imaging to compare the extent of atrophy and discriminative ability of the volumes of two temporal lobe structures, the entorhinal cortex and the hippocampus, between patients with Alzheimer disease and control subjects. METHODS: The study group consisted of 30 patients with probable Alzheimer disease diagnosed according to the National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) criteria and 32 healthy control subjects. The MR volumes of the entorhinal cortex and the hippocampus were used for the discriminant function and receiver operator characteristic analysis as well as multivariate analysis of variance for repeated measures to compare their discriminative power. RESULTS: Compared with control subjects, patients with Alzheimer disease had significantly smaller volumes of the entorhinal cortex and the hippocampus on both sides. Both the receiver operator characteristic and the discriminant function analyses using both volumes classified control subjects and Alzheimer patients with a high degree of accuracy (approximately 90%). Significant group x region interaction favoring hippocampal volumetry was determined by multivariate analysis of variance. CONCLUSION: The volumetric measurements of both the entorhinal cortex and hippocampus have comparably high discriminative power in diagnosing Alzheimer disease. In clinical practice, hippocampal volumetry may be more feasible, because the method is easier to use and has less variability. PMID- 9974070 TI - Venous hypertension associated with a posterior fossa dural arteriovenous fistula: another cause of bithalamic lesions on MR images. AB - We report a case of a posterior fossa arteriovenous fistula (AVF) with bithalamic hyperintensity of MR images. The thalamic abnormality improved after surgery, suggesting reversible venous hypertension as the pathogenesis of the finding, as opposed to infarction. This manifestation of a posterior fossa AVF should be considered in the differential diagnosis of bilateral thalamic disease. PMID- 9974071 TI - Complete duplication or extreme fenestration of the basilar artery. AB - We describe a 42-year-old man with complete duplication or extreme fenestration of the basilar artery. We review the developmental anatomy and embryology and discuss the possible clinical implications and associated findings of this anomaly. PMID- 9974072 TI - Metastatic adenopathy from nasopharyngeal carcinoma: successful response to radiation therapy assessed by color duplex sonography. AB - BACKGROUND AND PURPOSE: Although the role of gray-scale sonography for neck nodes is well documented, it plays a limited role in the evaluation of nodal response to treatment. This preliminary limited study sought to determine color duplex sonographic changes in successfully treated metastatic nodes from nasopharyngeal carcinoma. METHODS: Fourteen patients with nodal metastases from nasopharyngeal carcinoma were studied. A pretreatment sonogram was obtained for all patients. Patients were divided into two groups of seven: in one group, repeat sonograms were obtained 8 weeks after completion of treatment; in the second group, sonograms were obtained 16 weeks after treatment. The features studied included distribution of intranodal vascularity, resistive and pulsatility indexes, and peak systolic velocity. In 11 patients, follow-up sonograms were obtained 1 year after treatment. RESULTS: The majority (90%) of malignant nodes from nasopharyngeal carcinoma have an increased central and peripheral vascularity, a high resistive index (0.8), and a high pulsatility index (1.8). After radiation therapy to the nodes, a reduction in intranodal vascularity and a statistically significant reduction in the resistive index (0.58 to 0.59) and pulsatility index (0.91 to 0.93) are found. Although a similar reduction in the peak systolic velocity is observed, it is not statistically significant. CONCLUSION: Our preliminary findings suggest that after radiation therapy for malignant nodes in nasopharyngeal carcinoma, a reduction in intranodal vascularity is found, and the resistive and pulsatility indexes may return to benign parameters as early as 8 weeks after completion of treatment. PMID- 9974073 TI - Dilated venous plexus of the hypoglossal canal mimicking disease. AB - This article describes a case of prominent emissary veins of the hypoglossal canal protruding into the cerebellomedullary cistern mimicking disease, such as a nerve sheath tumor. The diagnosis and differentiation in this instance were confirmed by MR angiography and a review of alternative imaging planes. A diagnosis of hypoglossal canal lesions should be made with caution, as these lesions are quite rare, and vascular anomalies, such as those described, may mimic disease in this region. PMID- 9974074 TI - Pigmented villonodular synovitis of the temporomandibular joint: diagnostic imaging and endovascular therapeutic embolization of a rare head and neck tumor. AB - We report a case of pigmented villonodular synovitis involving the temporomandibular joint that presented as a rapidly growing tumor with extension through the skull base into the middle cranial fossa. The case is of interest not only because of the unusual extensive infiltration of this tumor but also because of the role modern diagnostic imaging and endovascular therapeutic techniques played in its diagnosis and management. PMID- 9974075 TI - Location of the primary motor cortex in schizencephaly. AB - BACKGROUND AND PURPOSE: Functional reorganization of the brain can result from congenital brain disorders as well as from brain infarction. The purpose of our study was to use functional MR imaging to determine whether reorganization of brain function occurs in patients with schizencephaly. METHODS: Four patients with schizencephaly (three right-handed, one ambidextrous) presented with seizures. Associated lesions included agenesis of the corpus callosum (n = 1) and absence of the septum pellucidum (n = 1). Functional MR imaging was performed in each patient using a single-section fast low-angle shot (FLASH) blood oxygen level-dependent (BOLD) technique at 1.5 T in a standard head coil. The motor cortex was initially identified on an axial T1-weighted anatomic image. Thirty consecutive images were obtained during a motor task consisting of repetitive finger-to-thumb opposition. The percentage of change in increased signal intensity was calculated for the primary motor area. An ipsilateral activation index was used to compare the affected with the unaffected hemisphere. RESULTS: The percentage of change in increased signal intensity in the area of activation ranged from 4.8% +/- 0.9 to 9.2% +/- 1.2 (mean, 5.6% +/- 1.5). The ipsilateral activation index in the affected hemisphere was 0.00 to 0.38, whereas that in the unaffected hemisphere was 15.4 to infinity. The difference in the ipsilateral activation index between each hemisphere was considered significant. CONCLUSION: Our results showed increased activation in the unaffected hemisphere in patients with schizencephaly, which may reflect functional reorganization of the motor area in patients with this congenital disorder. PMID- 9974076 TI - Polyarteritis nodosa presenting as temporal arteritis in a 9-year-old child. AB - A 9-year-old Haitian girl presented initially with monocular blindness and an isolated temporal arteritis, confirmed by angiographic studies and temporal artery biopsy findings. CT and MR studies of the intracranial circulation showed only an enlarged, dense superficial temporal artery. Systemic workup revealed a mildly elevated erythrocyte sedimentation rate, mild changes in white and red blood cells, and a remote history of sensorineural hearing loss. Pathologic examination of the biopsy specimen narrowed the differential diagnosis to giant cell temporal arteritis and polyarteritis nodosa. Treatment with corticosteroids alone failed, and the child returned 1 month later with severe systemic illness and encephalopathy. MR studies showed multiple cortical and subcortical foci of increased T2 signal, and gyriform enhancement on T1-weighted images. Renal and mesenteric arteriograms showed innumerable tiny aneurysms at branch points in small and medium-sized vessels, typical of polyarteritis nodosa. We found no previous reports of this initial presentation in the pediatric population for either polyarteritis nodosa or giant cell temporal arteritis. PMID- 9974077 TI - Encephalocraniocutaneous lipomatosis: complete neuroradiologic evaluation and follow-up of two cases. AB - Encephalocraniocutaneous lipomatosis (ECCL) is a rare neurocutaneous syndrome characterized by unilateral scalp, facial, and ocular lesions and ipsilateral cerebral malformations. To define the neuroimaging features of this disorder we studied two patients affected by ECCL and compared our data with those reported in the literature. Sonographic, CT, and MR imaging examinations showed quite specific CNS findings that are highly suggestive of the diagnosis of ECCL. To our knowledge this is the first report of a complete neuroradiologic evaluation and follow-up of this disorder. PMID- 9974078 TI - Surgically confirmed incorporation of a chronically retained neurointerventional microcatheter in the carotid artery. AB - A woman reported painful thrombosis of the superficial femoral artery 16 months after a transfemoral microcatheter was glued into a cerebral arteriovenous malformation and transected at the groin. When the catheter was removed, a portion was found to be incorporated into the wall of the carotid artery. This case demonstrates that portions of a retained microcatheter may be incorporated into the arterial wall while other portions may remain mobile and cause late peripheral arterial symptoms. PMID- 9974079 TI - Major complications of percutaneous embolization of skull-base tumors. AB - The technique of direct intratumoral injection of permanent liquid polymerizing agent was initially described in 1994 and has evolved significantly with experience. We report complications that occurred in two patients during injection of Histoacryl and offer suggestions to prevent such complications in the future. In one patient, the glue settled in the right middle cerebral artery; in the second, the glue entered the left ophthalmic artery through a collateral branch. Although the fundamental injection technique has not changed, we suggest additional precautions and modifications to make this procedure a safer and more valuable element in the overall management of patients with difficult skull-base tumors. PMID- 9974080 TI - The growth and development of the Annals of Human Biology: a 25-year retrospective. AB - The history of the founding in 1958 of the Society for the Study of Human Biology is outlined, and the circumstances in which the Annals of Human Biology began publication in 1974. The contents of the papers published 1974-1997 are reviewed; about 40% concern Population Biology, 40% Auxology and 20% Population Physiology. Some outstanding contributions in the first two of these fields are mentioned. Many consist of groups of papers from an ongoing study: 11 papers from the Otmoor villages study by Harrison and colleagues, and 11 concerning the growth of children in the Zurich Longitudinal Study, by Gasser and colleagues. Papers concerning the analysis of growth data and modelling of the growth curve, especially by Healy, are noted, and papers giving evidence of mini-spurts in growth and the saltation-stasis growth model are recalled. Wilson's papers on catch-up and growth regulation in twins are reviewed; also the contribution to growth-as-a-mirror of social conditions by workers at the Stockholm Institute of Education. The National Study of Health and Growth, led by Rona, contributed 13 papers over 14 years to the Annals, and there were outstanding one-off papers from the National Child Development Study, and the Cuban National Growth Study of 1972, and concerning the secular trend towards greater leg length in Japan, the upward social mobility of the taller of pairs of brothers, the growth of 18th century children in Vienna and Stuttgart and the measurements of 19th century slaves in the USA. PMID- 9974081 TI - Physiological variation and adaptability in human populations. AB - This review traces some of the developments in population physiology based on contributions to the Annals over the last 25 years. Two broad themes are evident, physiological systems variation and adaptation, and by way of introduction an historical perspective of their relationship within human ecology is explored. Studies of physical fitness and work capacity, and the efforts to create standardized field procedures make up a number of the early papers. Longitudinal studies have provided reliable reference standards for Westernized populations, but are virtually non-existent for primitive groups. The relative importance of phenotypic and genotypic variations in working capacity have yet to be clearly defined. The level of habitual activity during childhood contributes to the development of ventilatory capacity though constitutional influences are of major importance. Variability in strength and motor performance of skeletal muscles are shown to have a direct bearing on aspects of growth, development and biological maturation. Physical and psychological stress in communities have been investigated. These and other studies contribute valuable data on the issue of stress, hypertension and cardiovascular morbidity and mortality. On the theme of human adaptability, high altitude populations, variations in thermal tolerance and adaptations in ageing populations have all received recent investigation. Highland people of all ages have considerably larger lung volumes than coastal dwellers. Haematological, biochemical and pulmonary function show adaptive phenomena that vary in different highland groups. In the tropical biome, more recent work includes the functional consequences of malnutrition, ethnic and cultural differences in work capacity, and the effects of endemic disease on physical performance. Annals of Human Biology papers have more recently contributed to investigations on morphological and physiological changes with human ageing. Though there is a decline in the ability to adapt to environmental stresses with age this may be met by changes in adaptational strategy in physiological systems. PMID- 9974082 TI - The genetics of hand-clasping--a review and a familial study. AB - Hand-clasping refers to the preferential tendency for individuals to clasp the hands together. This paper reviews the previous literature on family data and twins, and reports new data. In this study about 55% of the population are left hand-claspers, 44% are right-hand-claspers, and the remaining 1% report that they have no preference or are indifferent. Familial data suggest that hand-clasping may be under genetic control: although the data do not fit any straightforward recessive or dominant Mendelian model, they are compatible with the type of model invoking fluctuating asymmetry which has been used to explain the inheritance of handedness and arm-folding. It is possible that hand-clasping, as for example arm folding, may be an idiosyncrasy due to or influenced by physical bilateral differences in the hands. All data together are suggestive of a genetic basis, although environmental influences are also evident. PMID- 9974083 TI - Hormonal factors in the development of differences in strength between boys and girls during adolescence: a longitudinal study. AB - The development of elbow flexor (biceps) and knee extensor (quadriceps) strength has been followed in a mixed longitudinal study of 50 boys and 50 girls from the age of 8 to 17 years. Sex differences in strength emerged at the time of peak height velocity and were especially marked for the biceps. Data for individual children were aligned to the time of peak height velocity and associations between strength, height, weight and circulating testosterone were investigated using multi-level modelling. The results show that, for girls, quadriceps strength is proportional to height and weight while for boys there is an additional factor which can be fully attributed to increasing levels of testosterone. Testosterone is important in explaining differences in biceps strength between the sexes but an additional factor is also required. It is suggested that, in addition to a direct effect on muscle, testosterone could have a second indirect action on biceps strength by promoting growth in length of the humerus as part of the general development of the male upper limb girdle. PMID- 9974084 TI - Strength and its relationship to changes in fat-free mass, total body potassium, total body water and IGF-1 in adults with growth hormone deficiency: effect of treatment with growth hormone. AB - The present investigation examined changes in strength in growth hormone deficient (GHD) adults following treatment with recombinant human growth hormone (rhGH), and assessed their relationship to changes in fat-free mass (FFM), total body potassium (TBK), total body water (TBW), the concentration of TBK and TBW per kg FFM, and insulin like growth factor-1 (IGF-1). The investigation was double-blind and placebo-controlled for a period of 6 months; this was followed by a period of open treatment for a further 6 months. Patients were assigned randomly to experimental (E) and control (C) groups. In the first 6 months group E received rhGH and group C placebo; in the second 6 months both groups received rhGH. Serial data were analysed for 23 males (11 group E, 12 group C) and 20 females (10 group E, 10 group C). Body composition was assessed by dual energy X ray absorptiometry, TBK and TBW. Muscle strength was recorded for arm flexion, leg extension and hand grip. Significant increases in FFM occurred in the first 6 months in group E (2.3 kg males, 1.4 kg females) and in the second 6 months in group C (2.4 kg males, 1.4 kg females). There was a modest increase in absolute strength with time, although only three increments were significant (knee extension in group E males and arm flexion in groups E and C females), all of which occurred during the 6-12 month period. Allometric scaling did not improve the identification of significant increments of strength. The mean concentrations of TBK (males 57.0-58.6, females 51.4-53.9 mmol) and TBW (males 0.65-0.69, females 0.65-0.68 l) per kg FFM, were significantly smaller at all stages of the trial than the reference values, suggesting that treatment had not fully normalized these variables. Likewise, the relationship between most of the increments of regional and total strength, and the corresponding increments of FFM, were generally poor and not significant. It was concluded that the reduced concentrations of TBK and TBW per kg FFM, which may be the effect of an inappropriate dose regime or mode of delivery, may, in part, contribute to the anomaly between increases in strength and FFM. PMID- 9974085 TI - Genetics of human body size and shape: evidence for an oligogenic control of adiposity. AB - In a previous study by the authors in each of the pedigree samples from Kirghizstan, Turkmenia and Chuvashia, four principal factors supposedly controlled by four non-overlapping gene subsets were found. About 90% of total variation of adiposity as assessed by 22 measurements of skinfolds, circumferences and indices were covered by these factors. This study provides results of segregation analysis of each of these four factors. By the usual transmission probability tests, major gene (MG) control was accepted in all 12 analyses--four traits in three populations. Some of the most parsimonious MG models included non-MG effects, such as correlation of residuals between spouses, between parent and offspring and between sibs. The Kirghizian samples showed a significant assortative mating effect as measured by the correlation between genotypic values at putative MG in spouses. The proportion of the trait variance attributable to the MG effect varied from 0.296 (factor F4 in the Chuvashia sample) to 0.596 (the same factor in the Kirghizian sample). It is assumed that four independent large-effect genes can be recognized in the genetic control of adiposity determining, respectively, individual predisposition to accumulate subcutaneous fat, its distribution between the body trunk and extremities, predisposition to accumulate inner fat and its distribution between the upper and lower body parts. In each population, unification of the four most parsimonious MG models forms oligogenic models explaining from 0.364 (Chuvashia) to 0.540 (Kirghizstan) of total adiposity. PMID- 9974086 TI - Age at menarche and urbanization in Cameroon: current status and secular trends. AB - Status quo data on the age at menarche were obtained on samples of Cameroonian girls living in urban (Yaounde) (n = 205), suburban (n = 505) and rural areas (n = 201). Mean ages at menarche, estimated by probit analysis, are 13.18 years (SD 1.08) in Yaounde, 13.98 years (SD 1.55) in the suburban area, and 14.27 years (SD 1.65) in the rural area. The early menarcheal age observed in Yaounde girls attending 'privileged schools' (12.72 years, SD 1.18) substantiates the hypothesis that in good environmental conditions Africans are as early-maturing as Asiatic or Mediterranean populations. Comparison with retrospective data on age at menarche during previous decades reveals the presence of a clear secular trend towards earlier maturation, at a rate of 2.5-3.2 months per decade, only in the main cities of the country (Yaounde/Douala) and a lack of temporal variation in rural areas. The degree of urbanization influences maturational age and its evolution, probably through improvements in the nutritional standards. PMID- 9974087 TI - [The main principles of the decrees on perinatal care]. PMID- 9974088 TI - [Can we improve the neuro-intellectual and behavioral prognosis of premature infants by modifying their environment?]. PMID- 9974089 TI - [Pediatrics in question]. PMID- 9974090 TI - [Cerebral anomalies associated with growth hormone insufficiency in children: major markers for diagnosis?]. AB - PATIENTS AND METHODS: The role of cerebral magnetic resonance imaging (MRI) in the diagnosis of growth hormone (GH) deficiency in children has been studied in 100 children. The diagnosis of GH deficiency was assessed at a mean age of 6.7 +/ 4.1 years: morphological abnormalities of the hypothalamic-pituitary (HP) region have been studied in three different groups: in the first group (70 cases), the neurohypophysis was present and normally located; in the second group (ten cases) it was missing; in the third group (20 cases) the neurohypophysis was ectopic (truncated stalk syndrome with ectopic neurohypophysis, small antehypophysis, thin or non-visualized stalk). RESULTS: In the majority of cases, children presenting with only one morphological abnormality of the HP region (ectopic neurohypophysis or small antehypophysis or non-visualized or thin stalk) had an isolated GH deficiency. When multiple morphological abnormalities were present, anterior pituitary deficiency was multiple in more than half the cases. Cerebral midline anomalies (above all Chiari I malformation and basipharyngeal canal) had been observed in 20% of the children presenting with GH deficiency. In the majority of cases (95%), these anomalies were associated with one or more abnormalities of the HP region. A familial case is reported: morphological anomalies of the HP region were different for both siblings. Genetic factors are evoked. CONCLUSION: The severity of the hormone deficiency is correlated to the ectopic location of the neurohypophysis, the thin appearance or non visibility of the pituitary stalk and the associated midline anomalies. PMID- 9974091 TI - [Contralateral transinguinal laparoscopy in unilateral inguinal hernia]. AB - BACKGROUND: Indication for surgical exploration of the contralateral groin during unilateral herniorraphy in children is the subject of a worldwide debate. Routine exploration based on the likelihood of a patent processus vaginalis (PV) according to age, gender or side to some extent leads to unnecessary procedures, while routine abstention may leave a peritoneal sac, likely to later induce a symptomatic hernia in about 10% of cases. METHODS AND PATIENTS: One hundred and twenty-five children aged from 1 month to 15 years underwent transinguinal laparoscopic assessment of the contralateral groin, using a 3 mm trocar and a 70 degrees telescope gently introduced through the exposed PV. Surgical exploration was performed only in those patients who exhibited a patent PV, and in patients where the groin was poorly visualized due to technical problems. RESULTS: Regardless of age, contralateral surgery was not considered in 88 (70%) of the 125 children. Among the 37 patients that were operated upon, eight had a negative exploration due to an erroneous endoscopic evaluation. Surgery was avoided in 35 (56%) of the 62 infants aged less than 2 years, including nine of the 13 prematures who were previously routinely operated upon. Conversely, in the 63 older patients who were readily spared from surgical exploration, the videoscopic evaluation allowed appropriate selection for contralateral surgery in six. CONCLUSION: A routine policy, either of surgery or observation, is no longer indicated as a quick, safe and cost-effective method is available to detect a patent PV. The transinguinal laparoscopy is safe and could be easily performed by surgeons already skilled in pediatric herniorraphy. Therefore, the videoscopic transinguinal contralateral evaluation is worth being promoted to ensure an appropriate surgery tailored to the anatomical features. PMID- 9974092 TI - [Sentinel surveillance of diarrhea in Ksar-Hellal (Tunisia)]. AB - BACKGROUND: In order to simplify the national data collection related to diarrhea, a sentinel surveillance system was implemented in the Ksar-Hellal district (Tunisia). POPULATION AND METHODS: This system was based on 461 cases of diarrhea collected from health centers and hospitals between June 1994 and December 1995. RESULTS: The collected information confirmed the previous data provided by the national system: frequency of diarrhea in health centers (4.14%), occurrence of the disease especially in the summer period, rate of hospitalization (10%) and low proportion of severe dehydration. The system also gave some new information related to the proportion of persistent diarrhea (7.1%), the low frequency of malnutrition (11%) and the etiology. CONCLUSION: The sentinel surveillance system validates information previously provided by the National Surveillance System. It also gave new information not obtained by the classical surveillance system. PMID- 9974093 TI - [Benign infantile convulsions. French collaborative study]. AB - BACKGROUND: Benign infantile non febrile seizures are not well known, leading us to study their clinical and EEG characteristics. METHODS: Between 1981 and 1994, we assembled 34 patients with the following inclusion criteria: non febrile seizures between 1 month and 2 years of age, normal personal history, no abnormality on clinical, biological and radiological investigations, normal developmental outcome with at least 1 year follow-up. RESULTS: These 34 patients were recognized as 14 familial cases (identical seizures affecting parents) and 11 non familial cases. The other nine cases had different or undefined epilepsy in the family. The clinical and EEG characteristics were the same: at the mean age of 6 months, brief partial seizures (often secondarily or apparently generalized) occurring in a cluster of two to 12 episodes a day for a mean duration of 2.5 days, with ictal EEG showing focal discharge, often slow waves or focal spikes on post-ictal tracing and normal interictal EEG. CONCLUSION: The clinical and EEG characteristics are important in order to recognize this type of infantile convulsions (familial or not familial), which have a good prognosis and need no aggressive treatment. PMID- 9974094 TI - [Benign intracranial hypertension: an unrecognized complication of corticosteroid therapy]. AB - BACKGROUND: Benign intracranial hypertension is due to an increased intracranial pressure of unknown cause. The initial symptoms, complications and associations with medical conditions are discussed. CASE REPORT: A 6-year-old girl developed symptoms of benign intracranial hypertension following reduction of oral corticosteroid therapy. Laboratory studies and head-computed tomographic scan were normal. Examination of the optic discs showed bilateral papilledema and the cerebrospinal fluid pressure was increased. The patient was given prednisone therapy 1 mg/kg daily initially, associated with acetazolamide, and removal of 25 mL of cerebrospinal fluid. All the symptoms resolved and the treatment was gradually decreased. The child developed no further visual failure. CONCLUSION: Benign intracranial hypertension with the risk of permanent visual loss is a complication underrecognized in children. All patients receiving large doses of the corticosteroids who complain of headache or blurring vision, particularly following a reduction of corticosteroid dosage, should have an ophtalmoscopic examination to exclude this complication. PMID- 9974095 TI - [Holoprosencephaly with neurogenic hypernatremia]. AB - BACKGROUND: Semi-lobar holoprosencephalies can be seldom complicated by neurogenic hypernatremia, which must be distinguished from other causes of hypernatremia. CASE REPORT: In two admitted children with semi-lobar holoprosencephaly, 7 months and 4 years old, biological data revealed chronic hypernatremia and hyperosmolarity without clinical signs of dehydration, which were finally attributed to a neurogenic hypernatremia. CONCLUSION: Neurogenic hypernatremia must be clearly differentiated from other causes of hypernatremia since it never causes specific complications. PMID- 9974096 TI - [Precocious puberty secondary to an intramedullary germinoma]. AB - BACKGROUND: hCG secreting tumors are responsible for 21% of precocious puberties in boys. Usual localizations are hepatic, cerebral, mediastinal and gonadic. CASE REPORT: A 4-year-old boy developed precocious puberty with rapid evolution. Serum beta hCG suggested germinal etiology, but radiological procedures failed to find any usual localization. Further occurrence of pain in the legs led to carry out a lumbar puncture. The high cerebrospinal fluid/blood gradient of beta hCG suggested the presence of an intramedullar tumor. Medullar magnetic resonance imaging found a large tumor facing L1 and L2. CONCLUSION: To our knowledge, this localization is described for only the second time. PMID- 9974097 TI - [Value of pulmonary gas exchange study during exercise in the diagnosis of a muscular glycogenosis]. AB - BACKGROUND: The diagnosis of muscular glycogen storage disease is usually difficult to demonstrate as symptoms normally consist of muscular cramps and exercise intolerance. Informations obtained from the study of the pulmonary gas exchange during exercise in a young patient with a glycogen storage disease are reported. CASE REPORT: The ventilatory and gas exchange responses to a cyclo ergometer exercise were studied in a 17-year-old girl during a ramp-like test (5 W/min). The temporal profile of CO2 production (VCO2) response was clearly abnormal: VCO2 was always lower than oxygen consumption throughout the test, reflecting the lack of lactate buffering by the bicarbonates due to the absence of lactate production. The respiratory ratio was still around 0.75 at the peak of the test. In contrast, responses were perfectly normal in the other members of the family, allowing rejection of the diagnosis of glycogen storage disease without any blood sampling. CONCLUSION: This case illustrates the benefit of studying pulmonary gas exchange during exercise for a non-invasive diagnosis of muscular glycogen storage disease and detection of the disease in the other members of family. PMID- 9974098 TI - [Benign familial infantile convulsions]. AB - Benign familial infantile convulsion is a syndrome recently identified among the epileptic seizures of infancy. The main characteristics are: occurrence before one year of age, brief epileptic bursts of partial type seizures with secondary generalization, excellent prognosis with normal mental and motor development, high familial incidence. This syndrome appears genetically heterogeneous. PMID- 9974099 TI - [Treatment of infantile visceral leishmaniasis]. AB - Visceral leishmaniasis is an endemic disease in the Mediterranean Basin. Children are one of the targets of the infection. Treatment usually requires parenteral injections of pentavalent antimony (Glucantime or Pentostam), but the high frequency of adverse events and the occurrence of primary or secondary resistance cases limit the use of these medications. Diamidines (Pentacarinat) or amphotericin B derivatives are alternatives to antimony. Unfortunately, pharmacokinetics and optimal dosage of diamidines are not well-known, and numerous adverse events are described. Liposomal preparations of amphotericin B enhance its efficiency and tolerance, and the duration of treatment may be reduced to 5 days. Moreover, primary resistance to amphotericin B is not described in immunocompetent children. Allopurinol associated with antimony seems no more efficient than antimony alone. Aminosidine is not evaluated. PMID- 9974100 TI - [Prenatal inhibition of intestinal vasoactive peptide and cerebral excitatory lesions in the newborn mouse]. AB - The glutamatergic agent ibotenate induces cortical plate and white matter lesions in the newborn mouse, mimicking brain lesions of the human neonate. In this model, co-treatment with ibotenate and a vasoactive intestinal peptide antagonist (VA) aggravates the excitotoxic lesions, suggesting a protective role of endogenous VIP. On the other hand, prenatal injection of VA is followed by a dramatic depletion of astrocytes in the neocortex. Since astrocytes produce numerous neuronotrophic agents, we studied the consequences of a decreased astrocytic density by prenatal VIP blockade on the excitotoxic brain lesions in newborn mice. Pregnant females were pre-treated with VA during the last 2 days of gestation and ibotenate was intracerebrally injected on postnatal day (P) 2 or P5. When compared to controls, pups pre-treated with VA and injected with ibotenate at P2 displayed a significant reduction of the white matter lesion size while cortical plate lesion was not affected. This protective effect disappeared when ibotenate was injected at P5. White matter protection by VA pre-treatment did not seem to be linked to the decreased astrocytic density since, i) this astrocytic paucity concerns only superficial cortical layers and does not affect white matter, ii) protective effects are only observed at P2 while astrocytic density reduction is observed at P2 and P5. This white matter protection could be secondary to an up-regulation of VIP receptors: an increased density of VIP receptors, which was described in other developmental models following VA treatment, could increase the efficacy of the endogenous VIP after an excitotoxic insult. PMID- 9974101 TI - [Precocious maturation of auditory evoked potentials in prematures: influence of gestational age and sex]. AB - In humans, the onset of the auditory function occurs at the beginning of the third trimester of pregnancy. Brainstem auditory evoked potentials (BAEPs) can be recorded in preterm neonates as early as 25-26 weeks of gestational age. The latency of BAEP waves show a significant decrease according to increasing age to achieve adult values at the end of the first month after birth for wave I and near 3 to 5 years old for waves III and V. Auditory evoked responses are influenced by gender, notably with significantly higher wave latencies in males than in females. These gender differences in auditory function appear early in humans, some being observed as soon as 34 weeks of gestational age. PMID- 9974102 TI - [Infant quality of life: criteria of parents and professionals. Development of an evaluation instrument]. AB - A survey was performed using open-ended questionnaires to be completed by parents or care-givers dealing with very young children (less than 3 years old) in order to study their opinions concerning the child's quality of life. About 800 questionnaires were analyzed with a content-analysis method. Nine categories and about 40 elementary criteria were distinguished. Some criteria were widely quoted. Others appeared useful to discriminate between care givers and parents, between different situations encountered by the child, and his/her age. This information will be used to develop a young child's quality of life scale. PMID- 9974103 TI - [Selective brain cooling]. AB - The brain is especially sensitive to heat stress. To limit the increase of intracranial heat in case of hyperthermia or fever, a system of selective cooling is put on. It includes two heat-exchangers. The first one, in the face and scalp skin, disperses calories through sweat evaporation. The second one is intracranial, close to the arteries which irrigate the brain. They are connected by a vascular network. In these conditions, the arterial blood temperature, of which cerebral temperature depends upon, is reduced by the cooled venous blood which comes from subcutaneous tissues through the skull wall. On feverish children, increasing such a selective cooling by face fanning can limit cerebral thermal stress. PMID- 9974104 TI - [Thermal comfort and fever or research on how to feel better]. AB - Thermic comfort is the affective perception of temperature (to be or not comfortable). It depends on the difference between thermoregulatory central set point and body temperature. Any measures which help to reduce this difference is felt as pleasant, and vice-versa. This must be taken into consideration in the prescriptions and advices for feverish children. Thus antipyretic therapy, and face fanning are always felt as pleasant, while undressing and tepid baths may be felt as unpleasant. PMID- 9974105 TI - [School refusal anxiety]. AB - School refusal mainly affects 11-13-year-old children but may be observed at any age from 5 to 15 years. It has two main clinical varieties: 1) school phobia in which the refusal attitude is directed toward school itself or an aspect of school environment; 2) separation anxiety in which the refusal of going to school is related to the separation with attached relatives, frequently the mother. Early recognition and intervention are determining factors for the prognosis. Hospital management and/or medication (imipramine) may be necessary in severe forms. PMID- 9974106 TI - [Convulsions after EMLA cream application]. PMID- 9974107 TI - [Fetal alcohol syndrome and pyloric stenosis]. PMID- 9974108 TI - [Effect of nitric oxide on the doppler profile of the anterior cerebral artery in the newborn]. PMID- 9974109 TI - [Neutropenia in a newborn secondary to sulfamethoxazole-trimethoprim administered to the mother]. PMID- 9974110 TI - [Bacterial meningitis in infants and children at the Brazzaville University Hospital]. PMID- 9974111 TI - [Epiglottitis: pathology in young children?]. PMID- 9974112 TI - [Infant growth formulas: useful for whom?]. PMID- 9974113 TI - [Baths for the treatment of fever: antiquated treatment, sham treatment?]. PMID- 9974114 TI - [Phototherapy and sudden infant death]. PMID- 9974115 TI - [Labyrinth malformation manifesting as pneumococcal meningitis]. PMID- 9974116 TI - Delayed behavioral effects following intrahippocampal injection of aggregated A beta (1-42). AB - Beta amyloid protein (A beta) is the major extracellular component of Alzheimer's disease (AD) plaques. In the current study, A beta (1-42) was aggregated in vitro using a method which produces A beta aggregates similar to those found in the AD brain. Twelve male Sprague-Dawley rats were trained in two-lever operant chambers under an alternating lever cyclic-ratio (ALCR) schedule. When performance was stable on the ALCR schedule, six subjects were injected (bilaterally into the CA3 area of the dorsal hippocampus) with 5.0 microliters aggregated A beta in suspension, and the remaining six subjects were injected with 5.0 microliters sterile water. Behavioral testing resumed 5 days after surgery and continued for 90 days post-injection. Aggregated A beta injection did not affect the number of lever switching errors made in a daily session but did affect the number of incorrect lever response perseverations. After approximately 30 days post injection, aggregated A beta injection detrimentally affected ability to track the changing parameters of the schedule, and decreased the efficiency by which subjects obtained reinforcers. From approximately day 50 post-injection onward, A beta-injected subjects demonstrated significantly higher numbers of incorrect lever response perseverations than did sterile water-injected subjects. These effects appeared to be central rather than peripheral, as A beta injection did not decrease running response rates under the ALCR schedule. The delayed onset of behavioral effects seen in this and other behavioral studies may be a result of a cascade of potentially harmful responses induced through glial activation following aggregated A beta injection. PMID- 9974117 TI - Apoptotic DNA fragmentation and upregulation of Bax induced by transient ischemia of the rat retina. AB - This study was performed to examine the involvement of apoptosis and the expression of bcl-2 family genes in ischemia-induced retinal injury. Retinal ischemia was induced in adult rats by raising the intraocular pressure to 130 mmHg for 45 min. Selective damage to the inner retina was observed 7 days after ischemia. No terminal deoxynucleotidyl-transferase (TdT)-mediated dUTP nick end labeling (TUNEL) positive cells were observed in the normal retina, but there was a significant number of TUNEL positive cells 6-48 h after transient ischemia followed by a decrease at 96 and 168 h. The number of TUNEL positive cells reached a maximum at 24 h after ischemia. DNA laddering was observed on agarose gel electrophoresis with the retinas 24 and 48 h after ischemia but not in the normal retina. Semiquantitative reverse transcription-polymerase chain reaction (RT-PCR) revealed that bax gene expression did not change immediately after cessation of ischemia, but gradually increased as early as 6 h, reached a peak at 24 h, then decreased to near baseline levels at 168 h. On the other hand, bcl-2 gene expression showed no obvious changes at any time after transient ischemia. Moreover, intense Bax protein immunoreactivity was detected in the retinal sections at 24 h after ischemia although little immunoreactivity was present in the normal sections. These results suggest that apoptosis associated with the expression of Bax is involved in retinal cell loss after ischemic insult. PMID- 9974118 TI - Neuronal activity in the lateral geniculate nucleus associated with ponto geniculo-occipital waves lacks lamina specificity. AB - Ponto-geniculo-occipital (PGO) waves are spontaneously occurring field potentials recorded in the dorsal lateral geniculate nucleus (LGN) just prior to and during rapid eye movement (REM) sleep. Facilitated discharge rates of LGN neurons are associated with PGO waves. In kittens during the critical period of visual system development, both visual experience and PGO waves appear capable of influencing the course of development through activity-dependent mechanisms. Retinal innervation of LGN segregates into eye-specific laminae and is critical to supporting the role of binocular visual experience in development. We sought to determine whether neuronal activity associated with PGO waves also exhibits lamina specificity. PGO wave-related discharges were examined in LGN neurons identified as to lamina location in adult cats administered urethane anesthesia and the reserpine-like compound, RO4-1284. Spontaneous activity of LGN neurons was related to the occurrence of PGO-like waves in all cells studied. No factors could be found that differentiated lamina location and PGO wave-related discharges. We conclude that the PGO wave influence on neuronal activity in the visual system is fundamentally different from that derived from visual experience. The implications of this difference for the role of the two sources of activation in the control of neural activity in development are discussed. PMID- 9974119 TI - Effect of dextromethorphan, a NMDA antagonist, on DNA repair in rat photochemical thrombotic cerebral ischemia. AB - Photochemical thrombotic ischemia model was used to study the possible roles of excision repair cross-complementing group 6 (ERCC6), a DNA repair gene, in the neuroprotection of dextromethorphan (DM), a NMDA antagonist, in ischemic brain injury. The results showed that no obvious ERCC6 mRNA expression was found in the perifocal area of irradiated cerebral cortex before 24 h postischemia. Then, the number of ERCC6 mRNA positive cells gradually enhanced, and attained a peak value at 72 h after light irradiation, which followed a declined tendency at 7-day postlesion. These results suggest that DNA repair gene ERCC6 mRNA expression in the perifocal area may be involved in the pathophysiological processes following the photochemical thrombotic cerebral ischemia. By the administration of DM, we observed that it can significantly upregulate the expression of ERCC6 mRNA in the perifocal area at 48 h after ischemic event. The neuroprotective mechanisms of DM may be related to the upregulation of DNA repair gene ERCC6 mRNA. PMID- 9974120 TI - Peripheral administration of novel anti-inflammatories can attenuate the effects of chronic inflammation within the CNS. AB - In the present study we investigated whether nitroflurbiprofen (NFP) or nitro aspirin can reduce the inflammatory response induced by continuous infusion of lipopolysaccharide (LPS) into the fourth ventricular space of the rat's brain for 30 days. The chronic LPS infusion produced an extensive inflammation that was particularly evident in the hippocampus, subiculum and entorhinal and piriform cortices. Daily peripheral administration of NFP dose-dependently, and significantly, attenuated the brain inflammation as indicated by the decreased density and reactive state of microglial cells. Daily peripheral administration of nitro-aspirin also attenuated the brain inflammation, but to a much lesser degree than NFP. The results demonstrated that nonsteroidal anti-inflammatory drugs (NSAIDs) could reduce brain inflammation and that NFP is an effective anti inflammatory agent. PMID- 9974121 TI - Effect of selegiline on dopamine concentration in the striatum of a primate. AB - Monoamine oxidase (MAO) has two subtypes, A and B, that have different distributions between the rodent and the human. In the striatum, dopamine (DA) of the rat seems to be metabolized by MAO A, and DA of the human is largely deaminated by MAO B. MAO in the striatum of common marmosets is also type B. Using in vivo microdialysis, we investigated the pharmacological activity of selegiline, a selective irreversible inhibitor of MAO B, in the striatum of marmosets. Intraperitoneal co-administration of selegiline (1 mg kg-1, i.p.) with levodopa/carbidopa (10/2.5 mg kg-1, i.p.) did not significantly increase extracellular concentration of DA in the striatum of common marmosets compared with control animals receiving levodopa/carbidopa alone. Daily pretreatment with 0.1 mg kg-1 (i.p.) selegiline for two weeks, however, dramatically increased extracellular concentration of DA to about seven times that of control animals treated with levodopa/carbidopa alone in marmosets. Such an increase in extracellular concentrations of DA could not be observed in a similar study with Wistar rats. This study showed that chronic administration of a small dose of selegiline caused a marked increase in extracellular DA concentration in the striatum of primates, but not in the rodents. PMID- 9974122 TI - Rapid effects of corticosterone on cardiovascular neurons in the rostral ventrolateral medulla of rats. AB - The present study has explored possible fast actions of corticosteroid hormones on activity of cardiovascular neurons of the rostral ventrolateral medulla. Experiments were conducted in 60 urethane-anesthetized, artificially ventilated adult rats. Extracellular recordings of unitary firings were made from the RVLM with multi- or single-barreled microelectrodes. Barosensitive cardiovascular neurons were identified through activation of the baroreceptor reflex by electrical stimulation of the aortic nerve and by intravenous injection of phenylephrine. In 52 barosensitive cardiovascular neurons, iontophoretically applied corticosterone sulfate increased the ongoing activity of 30 (57.7%) neurons, the other 22 (42.3%) neurons being unaffected. In 16 bulbospinal pre sympathetic neurons, iontophorized corticosterone increased the firing rate of 12 neurons. Intravenously applied corticosterone (0.2 mg) increased the firing rates of 5 out of 12 bulbospinal pre-sympathetic neurons. The average baseline activity of cardiovascular neurons sensitive to corticosterone was found to be significantly less than that of the cardiovascular neurons insensitive to corticosterone. In 64 non-cardiovascular neurons, the firing rate of 13 (20.3%) neurons increased, 23 (36.0%) decreased and 28 (43.7%) remained unchanged following local application of corticosterone. The changes in firing rates of RVLM neurons following application of corticosterone occurred rapidly and were dependent on the doses of the agent. RU-38486 was able to reduce or block the rapid effects of corticosterone on cardiovascular and non-cardiovascular neurons. The results demonstrated that corticosterone may fast, non-genomically, modulate the activity of central regulators of the cardiovascular system and suggested that fast non-genomic actions of corticosteroid hormones may be an important mechanism in the integration of the autonomic nervous and the cardiovascular systems during some conditions such as stress. PMID- 9974123 TI - Regenerative effect of human recombinant NGF on capsaicin-lesioned sensory neurons in the adult rat. AB - Nerve growth factor (NGF) has the ability to increase the content of peptide transmitter in intact primary sensory afferents of the adult rat. We have previously shown that NGF can also induce a refill of peptide transmitters in capsaicin-depleted peptidergic nerve terminals of the rat paw skin upon intraplantar injection. The present study was aimed at investigating the neurochemical, immunohistochemical and functional recovery of peripheral and central terminals of capsaicin-lesioned afferents following administration of recombinant human NGF-beta (rhNGF-beta). The systemic capsaicin treatment in adult rats by 50 mg/kg s.c. (day 0) was followed by intraplantar rhNGF-beta injections (4 micrograms each) into one hind paw on days 1, 2, 3, 5, 6 and by the analysis on day 8. The content of the marker peptide calcitonin gene-related peptide (CGRP) showed a 100% NGF-induced recovery in the peripheral (sciatic nerve) and central axons (lumbar dorsal roots) on the side of the NGF treatment and also in the contralateral sciatic nerve and lumbar dorsal roots. In the terminals of the hind paw skin, the recovery of the CGRP content, as measured by radioimmunoassay, was 100% in the plantar and 80% in the dorsal skin ipsilaterally, and 55% in the dorsal and plantar hind paw skin contralaterally. In the lumbar dorsal spinal cord, CGRP content recovered by 85% bilaterally. The morphological appearance of the sensory nerve terminals was visualized by CGRP immunohistochemistry. In the paw skin, the CGRP-immunoreactive (CGRP-IR) nerve endings were restricted to a fragmentary subepidermal plexus after the capsaicin treatment, whereas the subsequent NGF treatment caused a bilateral recovery of the subepidermal plexus and an intact reinnervation of the epidermis and blood vessels with free nerve terminals. The capsaicin-induced fragmentation of the CGRP terminal plexus in laminae I and II of the lumbar spinal dorsal horn was also markedly repaired on both sides by the intraplantar NGF injections. The NGF treatment caused the CGRP nerve terminals in the spinal cord to regain their ability of releasing transmitter upon capsaicin stimulation as shown in tissue slice superfusion experiments. These results show that within one week, rhNGF beta can induce a complete reinnervation of skin and spinal cord with intact CGRP IR nerve terminals after an acute capsaicin lesion. PMID- 9974124 TI - Regulation of the expression of peripheral benzodiazepine receptors and their endogenous ligands during rat sciatic nerve degeneration and regeneration: a role for PBR in neurosteroidogenesis. AB - Peripheral benzodiazepine receptors (PBR) and their endogenous ligands, the diazepam-binding inhibitor derived-peptides, are present in Schwann cells in the peripheral nervous system. The aim of this study was to determine the influence of reversible (freeze-injury) and permanent (transection and ligature) nerve lesion on PBR density and on the levels of their endogenous ligands, by autoradiography (using [3H]PK11195) and radioimmunoassay (using antisera directed against the octadecaneuropeptide (ODN), a diazepam-binding inhibitor fragment). The potential role of PBR on peripheral nerve steroidogenesis, was studied by investigating the effect of specific PBR agonists and antagonists on pregnenolone levels in the sciatic nerve. Sixteen to 30 days after nerve lesion, PBR density and ODN-LI level were highly increased. Their expression returned to normal level when regeneration was completed 60 days after freeze-injury, but remained elevated when regeneration did not occur in transected distal stumps. Reverse phase HPLC analysis of ODN-LI showed that in control nerve extracts, the major immunoreactive peak co-elutes with triakontatetraneuropeptide (TTN). After freeze injury, intermediate molecular forms eluting between ODN and TTN were predominant and remained elevated at day 60. The greater accumulation of intermediate forms when regeneration is allowed to occur may indicate a particular role of these forms in axonal elongation and myelination. Ro5-4864, a high affinity PBR agonist increased pregnenolone concentration in the sciatic nerve. This effect was antagonised by PK11195, a high affinity PBR antagonist, which had no effect on pregnenolone basal level, indicating a specific action of PBR in neurosteroid production. These results suggest a role for PBR and their endogenous ligands in peripheral nerve regeneration. A trophic effect could be exerted via stimulation of steroid synthesis. PMID- 9974125 TI - Net efflux of cysteine, glutathione and related metabolites from rat hippocampal slices during oxygen/glucose deprivation: dependence on gamma-glutamyl transpeptidase. AB - Extracellular metabolism of the protective substance glutathione (gamma-glutamyl cysteinyl-glycine) may generate cysteine, glycine, several gamma-glutamyl containing dipeptides and possibly free glutamate, all of which could participate in neurotoxicity. In the present study, we have examined how blockage of gamma glutamyl transpeptidase, the key enzyme in glutathione degradation, influences the extracellular concentrations of glutathione, cysteine and related metabolites during anoxia/aglycemia of rat hippocampal slices. The net efflux, i.e., the increase in extracellular concentration due to changes in release and/or uptake, of cysteine, cysteine sulfinate, gamma-glutamyl-glutamate, gamma-glutamyl glutamine, glutathione, gamma-glutamyl-cysteine and glutamate increased as a result of anoxia/aglycemia. These increases in net efflux of cysteine, cysteine sulfinate, gamma-glutamyl-glutamate and gamma-glutamyl-glutamine were reduced or blocked by acivicin, an inhibitor of gamma-glutamyl transpeptidase. In contrast, acivicin caused an increase in both basal and anoxia/aglycemia-induced net efflux of glutathione whereas the basal and anoxia/aglycemia-induced efflux of glutamate was unchanged by acivicin treatment. The effect of acivicin on the efflux of gamma-glutamyl-cysteine was similar to that of glutathione although less pronounced. Addition of beta-mercaptoethanol to the incubation medium during and after 30 min of anoxia/aglycemia decreased the net efflux of cysteine sulfinate specifically, indicating that the increase in cysteine sulfinate during anoxia/aglycemia may be partly derived from the spontaneous oxidation of cysteine. The results suggest that gamma-glutamyl transpeptidase may be involved in the regulation of the extracellular concentrations of cysteine, several gamma glutamyl-containing dipeptides and glutathione but not glutamate during ischemia. PMID- 9974126 TI - Down-regulation of cannabinoid receptor agonist-stimulated [35S]GTP gamma S binding in synaptic plasma membrane from chronic ethanol exposed mouse. AB - In our previous study, we demonstrated that chronic ethanol (EtOH) exposure down regulated the cannabinoid receptors (CB1) in mouse brain synaptic plasma membrane (SPM) (Basavarajappa et al., Brain Res. 793 (1998) 212-218). In the present study, we investigated the effect of chronic EtOH (4-day inhalation) on the CB1 agonist stimulated guanosine-5'-O-(3-[35S]thio)-triphosphate ([35S]GTP gamma S) binding in SPM from mouse. Our results indicate that the net CP55,940 stimulated [35S]GTP gamma S binding was increased with increasing concentrations of CP55,940 and GDP. This net CP55,940 (1.5 microM) stimulated [35S]GTP gamma S binding was reduced significantly (-25%) in SPM from chronic EtOH group (175 +/- 5.25%, control; 150 +/- 8.14%, EtOH; P < 0.05). This effect occurs without any significant changes on basal [35S]GTP gamma S binding (152.1 +/- 10.7 for control, 147.4 +/- 5.0 fmol/mg protein for chronic EtOH group, P > 0.05). Non linear regression analysis of net CP55,940 stimulated [35S]GTP gamma S binding in SPM showed that the Bmax of cannabinoid stimulated binding was significantly reduced in chronic EtOH exposed mouse (Bmax = 7.58 +/- 0.22 for control; 6.42 +/- 0.20 pmol/mg protein for EtOH group; P < 0.05) without any significant changes in the G-protein affinity (Kd = 2.68 +/- 0.24 for control; 3.42 +/- 0.31 nM for EtOH group; P > 0.05). The pharmacological specificity of CP55,940 stimulated [35S]GTP gamma S binding in SPM was examined with CB1 receptor antagonist, SR141716A and these studies indicated that CP55,940 stimulated [35S]GTP gamma S binding was blocked by SR141716A with a decrease (P < 0.05) in the IC50 values in the SPM from chronic EtOH group. These results suggest that the observed down-regulation of CB1 receptors by chronic EtOH has a profound effect on desensitization of cannabinoid-activated signal transduction and possible involvement of CB1 receptors in EtOH tolerance and dependence. PMID- 9974127 TI - Lesions of the nucleus basalis magnocellularis do not impair prepulse inhibition and latent inhibition of fear-potentiated startle in the rat. AB - The present study tested if lesions of the nucleus basalis magnocellularis (NBM) affect prepulse inhibition (PPI) of the acoustic startle response and latent inhibition (LI) of fear-potentiated startle. The NBM is known to play an important role in learning and memory. Recently, the interest of research focused on its role in attentional and response selection processes. We here tested the effect of excitotoxic NBM-lesions on PPI, a phenomenon of sensorimotor gating that occurs at early stages of information processing. We also assessed the lesion effects on LI, a phenomenon of reduced conditioning after stimulus preexposure that can be used to measure selective attention. Bilateral infusions into the NBM of 80 nmol of quinolinic acid markedly reduced the number of choline acetyltransferase immunopositive neurons in the NBM and lead to a pronounced reduction of acetylcholine esterase in the cortex and the amygdala. However, no effects on PPI, fear-conditioning, or LI of fear-potentiated startle were found. Therefore, we conclude that there is no NBM-driven attentional or response selection process involved in PPI. Furthermore, the simple association learning in the classical conditioning paradigm used for fear-potentiated startle or LI is unaffected by NBM-lesions. PMID- 9974128 TI - On the effect of chemically activated fine muscle afferents on interneurones mediating group I non-reciprocal inhibition of extensor ankle and knee muscles in humans. AB - In a previous paper it was shown that muscle nociceptive discharge depressed the activity of interneurones mediating group I non-reciprocal inhibition (or Ib interneurones) in humans [A. Rossi, B. Decchi, Changes in Ib heteronymous inhibition to soleus motoneurons during cutaneous and muscle nociceptive stimulation in humans, Brain Res. 774 (1997) 55-61.]. However, since nociceptive discharge depressed the size of the soleus H-reflex (by which Ib inhibition was tested) the question arises as to whether modification of motoneurone membrane conductance per se could depress the size of Ib inhibitory post-synaptic potentials. The results of the present study suggest that the contribution of motoneurone hyperpolarization to Ib disinhibition is negligible and that muscle nociceptive discharge actually depresses the activity of these pathways. PMID- 9974129 TI - Ecto-ATPase activity in cerebellum: implication to the function of synaptic transmission. AB - The involvement of ATP in synaptic transmission was examined in synapses on granule cells of the rat cerebellum using ecto-ATPase activity. Reaction product was found in a majority but not all synapses between axodendritic, axoaxonic, and dendrodendritic appositions of granule cells and was associated with extracellular surface of both pre- and postsynaptic membranes. Specificity of the detection was justified by using diethyl pyrocarbonate, specific inhibitor of ecto-ATPase activity. These observations provide direct morphological evidence in support of the view that ATP participates in synaptic transmission and indicate functional heterogeneity of synapses in cerebellum. PMID- 9974130 TI - Neurokinin-1 receptors and spinal cord control of blood pressure in spontaneously hypertensive rats. AB - In this study we examined blood pressure and heart rate responses to intrathecal administration of a synthetic NK1-receptor agonist, H2N-(CH2)4-CO-Phe-Phe-Pro NmeLeu-Met-NH2 (GR 73,632), in spontaneously hypertensive rats (SHR) and their progenitor strain, the Wistar-Kyoto rat (WKY). Sodium pentobarbitone anaesthetised rats with implanted intrathecal catheters were paralysed (pancuronium dibromide) and artificially ventilated. Injection of GR 73,632 at the T9 spinal level evoked dose-dependent increases in mean arterial pressure (MAP) in WKY and SHR. SHR had a lower MAP response threshold than WKY but increase in response with increasing dose was less in SHR than WKY. Biphasic blood pressure responses at high doses were observed in both strains. Prior administration of the NK1-receptor antagonist (3 aR,7aR)-7,7-diphenyl-2-[1-imino 2(methoxyphenyl)ethyl] perhydroisoindol-4-one (RP 67,580) significantly reduced the pressor response in WKY but not SHR. The depressor response was not attenuated in either strain. PMID- 9974131 TI - Effects of electrical stimulation of the tentacular digits of a slug upon the frequency of electrical oscillations in the procerebral lobe. AB - To find the primary mechanism for the frequency changes of electrical oscillations in the procerebral (PC) lobe of a slug, we electrically stimulated the tip, middle and basal regions of the digits of the superior and inferior tentacles and recorded the local field potentials from the PC lobe. Stimuli to the middle and basal regions of the digits of the inferior tentacle significantly decreased the frequency of electrical oscillations in the PC lobe, whereas those to the tip regions of the digits of the inferior tentacle and all regions of the digits of the superior tentacle increased it. These findings suggest that the change in the frequency of electrical oscillations in the PC lobe depends on the excited region in the digits, providing the first presentation of the physiological difference in the olfactory function between the superior and inferior tentacles. PMID- 9974132 TI - 5-HT agonist-induced phase-advances of the circadian pacemaker are diminished by chronic antidepressant drug treatment. AB - Serotonin (5-HT) and its agonists alter the timing of the circadian pacemaker. Previous research has shown that when they are injected 4 h before or after the onset of wheel-running, they phase-advance or delay, respectively, the timing of the pacemaker. Because serotonergic interventions alter 5-HT receptor number in the hypothalamus, we asked whether chronic treatment with an antidepressant drug (AD) that modifies serotonergic function could alter the phase-shifting effects of the 5-HT agonist 8-hydroxydipropylaminotetralin (8-OH-DPAT). Hamsters were treated chronically with the monoamine oxidase inhibitor (MAOI), clorgyline, and then injected with 8-OH-DPAT or vehicle (VEH) either 4 h before or after the onset of wheel-running. MAOI treatment decreased the magnitude of both 8-OH-DPAT- and VEH-induced phase advances, but not the magnitude of 8-OH-DPAT-induced phase delays. The results indicate that 8-OH-DPAT-induced phase-advances and delays are functionally distinct with regard to adaptive changes during chronic AD treatment. PMID- 9974134 TI - BDNF-dependent enhancement of exocytosis in cultured cortical neurons requires translation but not transcription. AB - Neurotrophic factors, such as brain-derived neurotrophic factor (BDNF), are involved in acute modulation of synaptic plasticity. Different modes of action of BDNF have been described with time courses ranging from seconds to hours, but the sequence of cellular processes responsible for BDNF-dependent modulation of synaptic plasticity is unknown. We have used optical imaging of the styryl dye, FM1-43, which selectively labels synaptic vesicles, to investigate potential presynaptic effects of BDNF. Addition of BDNF to cultured cortical neurons for 3 h produced a significant enhancement of exocytosis upon modest depolarization. BDNF had no effect on exocytosis either immediately or after incubation for 30 min. BDNF-dependent enhancement of exocytosis was blocked by the tyrosine kinase inhibitor, K252a, but not by K252b, consistent with signalling via the TrkB receptor. Having demonstrated that the BDNF-dependent enhancement of synaptic vesicle release was present only after 1 h, we investigated whether de novo gene transcription and/or protein synthesis were involved. Addition of the inhibitors of RNA synthesis, actinomycin D, or 5,6-dichloro-1-beta-D-ribofuranosyl benzimidazole (DRB), did not affect the enhancement of exocytosis produced by BDNF. However, the effect of BDNF was blocked by the inhibitors of translation, cycloheximide or anisomycin. Our results indicate a rapid BDNF-dependent enhancement of neurotransmitter release that requires translation but not transcription. PMID- 9974133 TI - Neuroprotective action of a novel compound--M50463--in primary cultured neurons. AB - The neuroprotective effects of a novel synthetic compound, M50463, have been determined by using embryonic rat neocortical neurons in various culture conditions. M50463 was initially characterized as a potent specific ligand for a voltage-dependent sodium channel by radioligand binding studies. In fact, M50463 inhibited neuronal cell death induced by veratrine and inhibited an increase of the intracellular calcium level in neurons evoked by veratrine. In addition to such expected effects, M50463 had the ability to prevent glutamate neurotoxicity, to promote the neuronal survival in serum-deprived medium and to prevent nitric oxide-induced neurotoxicity. These results suggested that M50463 is not a simple sodium channel blocker, but a neuroprotective agent which has some crucial mechanism of action on neuronal death occurring in various situations, and it is a novel, innovative candidate for neuroprotective therapy for various neurodegenerative disorders. PMID- 9974135 TI - Preferential injury of oligodendroblasts by a short hypoxic-ischemic insult. AB - One-week-old rat pups were subjected to an acute 10 min severe hypoxic-ischemic insult. Over the next 24 h, during the reperfusion period, O4 immunocytochemistry demonstrated that oligodendroblasts underwent degenerative changes that were coincident with induction of heme oxygenase. We suggest that the increased vulnerability of oligodendroblasts to oxidative stress following an hypoxic ischemic insult may contribute to the pathogenesis of periventricular leukomalacia. PMID- 9974136 TI - Neurons of the rat suprachiasmatic nucleus show a circadian rhythm in membrane properties that is lost during prolonged whole-cell recording. AB - The suprachiasmatic nucleus is commonly considered to contain the main pacemaker of behavioral and hormonal circadian rhythms. Using whole-cell patch-clamp recordings, the membrane properties of suprachiasmatic nucleus neurons were investigated in order to get more insight in membrane physiological mechanisms underlying the circadian rhythm in firing activity. Circadian rhythmicity could not be detected either in spontaneous firing rate or in other membrane properties when whole-cell measurements were made following an initial phase shortly after membrane rupture. However, this apparent lack of rhythmicity was not due to an unhealthy slice preparation or to seal formation, as a clear day/night difference in firing rate was found in cell-attached recordings. Furthermore, in a subsequent series of whole-cell recordings, membrane properties were assessed directly after membrane rupture, and in this series we did find a significant day/night difference in spontaneous firing rate, input resistance and frequency adaptation. As concerns the participation of different subpopulations of suprachiasmatic nucleus neurons expressing circadian rhythmicity, cluster I neurons exhibited strong rhythmicity, whereas no day/night differences were found in cluster II neurons. Vasopressin-containing cells form a subpopulation of cluster I neurons and showed a more pronounced circadian rhythmicity than the total population of cluster I neurons. In addition to their strong rhythm in spontaneous firing rate they also displayed a day/night difference in membrane potential. PMID- 9974138 TI - Rapid cloning of cDNA ends polymerase chain reaction of G-protein-coupled receptor kinase 6: an improved method to determine 5'- and 3'-cDNA ends. AB - Rapid cloning of 5'- and 3'-cDNA ends polymerase chain reaction (5'-/3'-RACE-PCR) is useful to determine unknown 5'- and 3'-cDNA termini. Even if the method can yield complete cDNA sequences within a couple of days, the RACE procedure bears some characteristic traps and often results in amplification of unspecific PCR products. Here we used improved 5'- and 3'-RACE-PCR protocols to obtain the complete cDNA sequence of the G-protein-coupled receptor kinase 6 (GRK6) from a rat brain cDNA library. The use of an anchored oligo-(dT)16-V-primer in the cDNA synthesis, the addition of single-sided PCR steps prior to the RACE-PCRs and the optimization of the dA-tailing reaction conditions in 5'-RACE enhanced RACE-PCR efficiency. Taken together, the method is a tool to determine unknown 5' and 3' cDNA ends and enables the detection of different transcription initiation sites and mRNA splice variants even from small tissue samples like distinct brain regions. The extensive troubleshooting section discusses typical problems of each substep and contains additional references for support protocols. PMID- 9974137 TI - Highly sensitive radioactive in situ hybridization using full length hydrolyzed riboprobes to detect alpha 2 adrenoceptor subtype mRNAs in adult and developing rat brain. AB - The mRNA expression of highly homologous alpha 2 adrenoceptor subtypes was determined using a highly sensitive in situ hybridization protocol that allowed the detection of low abundance mRNA. Full-length 35S-labeled riboprobes specific for alpha 2A, alpha 2B and alpha 2C adrenoceptors were used for maximal sensitivity. The probes were hydrolyzed to an average length of 600 bp which, in combination with proteinase K digestion, resulted in optimal probe penetration in developmental and adult tissue. The expression intensity could be quantified and the ontogeny of receptor mRNA expression determined. At the same time receptor binding sites or functional proteins could be detected simultaneously in adjacent sections, because fresh frozen and post-fixed tissue was used. PMID- 9974139 TI - Anoxic and hypoxic immature rat model for measurement of monoamine using in vivo microdialysis. AB - The immature brain is considered relatively resistant to anoxia and ischemia. Although hypoxia without ischemia has not been considered to produce brain damage in immature rats as well as in adult rats (S. Levine, Anoxic-ischemic encephalopathy in rats, Am. J. Pathol., 36 (1960) 1-17 [8]; D.E. Levy, J.B. Brieley, D.G. Silverman, F. Plum, Brief hypoxia-ischemia initially damages cerebral neurons, Arch. Neurol., 32 (1975) 450-456 [9]; J.E. Rice, R.C. Vannucci, J.B., Brieriey, The influence of immaturity on hypoxic-ischemic brain damage in rat, Ann. Neurol., 9 (1981) 131-141 [14]), hypoxia in postnatal period is possible to cause a functional brain damage (T. Hender, P. Lundborg, Regional changes in monoamine synthesis in the developing rat brain during hypoxia, Acta. Physiol. Scand., 106 (1979) 139-143 [3]; W. Ihle, J. Gross, R. Moller, Effect on chronic postnatal hypoxia on dopamine uptake by synaptosomes from striatum of adult rats, Biomed. Biochem. Acta., 44 (1985) 433-437 [7]; A. Lun, J. Gross, M. Beyer, H.D. Fischer, C. Wustmann, J. Schmidt, K. Hecht, The vulnerable period of perinatal hypoxia with regard to dopamine release and behavior in adult rats, Biomed. Biochem. Acta., 45 (1986) 619-627 [10]). Using microdialysis, we studied the anoxic or hypoxic effect on catecholamine metabolism in immature rat brain by measuring extracellular concentrations of norepinephrine (NE), dopamine (DA), and its metabolites and also 5-hydroxyindole-3-acetic acid (5-HIAA), the serotonin metabolite. DA is a well established excitatory neurotransmitter (R.C. Vannucci, Experimental biology of cerebral hypoxia-ischemia: relation to perinatal brain damage, Pediatr. Res., 27 (1990) 317-326 [16]), and in the previous report using hypoxic 7-day-old rat pups increase of DA was not detected without additional stimulations (K. Gordon, D. Johnston, M.V. Robinson, T.E. Statman, J.B. Becker, F. Silverstein, Transient hypoxia alters striatal catecholamine metabolism in immature brain: An in vivo microdialysis study, J. Neurochem., 54 (1990) 605-611 [2]). Whereas recently in newborn piglets, hypoxic hypoxia produced increase of extracellular DA (C.-C. Huang, N.S. Lajevardi, O. Tammela, A. Pastuszko, Relationship of extracellular dopamine in striatum of newborn piglets to cortical oxygen pressure, Neurochem. Res., 19 (1994) 649-655 [6]; Olano, M., Song, D., Murphy, S., Wilson, D. F. and Pastuszko, A., Relationships of dopamine, cortical oxygen pressure, and hydroxyl radicals in brain of newborn piglets during hypoxia and posthypoxic recovery, J. Neurochem., 65 (1995) 1205-1212 [13]). We consider that hypoxic ischemic brain damage of human newborns that we can treat is a damage, which does not show overt neuropathological changes. We therefore tried to show that transient anoxia and hypoxia caused biochemical alteration if the exposure did not produce marked morphological changes. This rodent model is adequate to study perinatal asphyxia and alteration of monoamine level could be useful for evaluation of brain damage, even if it is not detected histologically. PMID- 9974140 TI - A simple pressure microinjecting system for delivery of small substance volumes to the brain: application to the developmental study of thalamo-cortical projections in foetal and neonatal rats. AB - We describe a reliable and inexpensive method for placing injections of anatomical tracers into the brain of lower mammals. The pressure microinjecting system we developed is specifically designed to deliver very small amount of substances. The injecting portion of the system is relatively easy to assemble and can be repeatedly used for multiple experimental sessions. The system has been validated with experiments of multiple fluorescent retrograde tracing. In these experiments the populations of thalamo-cortical neurons were consistently labeled by the tracers injected bilaterally and symmetrically in the cortex of foetal and neonatal rats. PMID- 9974141 TI - An optimised procedure for prenatal ethanol exposure with determination of its effects on central nervous system connections. AB - We describe the protocol set-up to investigate an experimental model of foetal alcohol syndrome in the rat. The protocol has been devised to expose specific cell populations of the central nervous system to ethanol during their neurogenesis and has been applied to the study of diencephalo-telencephalic connections. We were able to demonstrate specific permanent changes of the adult thalamo-cortical circuitry. Our protocol can be applied to study other aspects of central nervous system-ethanol interactions, such as neurotransmitter and receptor patterns. It can also represent a useful tool to test the effects of different diets to prevent nutritional deficiencies and the efficacy of drug treatments to prevent foetal alcohol syndrome. We have shown in fact that ethanol induced thalamo-cortical alterations are partially prevented by concurrent administration of acetyl-L-carnitine. Finally, the present protocol can be used to investigate the effects of ethanol exposure on the development of different brain structures. To this purpose, the gestational period for ethanol exposure must be chosen according to the peak of neurogenesis for the investigated structure. PMID- 9974142 TI - An on-line method for the measurement of total protein output in biological fluids and secretory tissues after stimulation of intrinsic nerves and identification of neurotransmitters using immunohistochemical techniques. AB - Proteins are essential ingredients of life and thus it is essential to measure the level of proteins in biological fluids and tissue homogenates. Several methods have previously been described in the literature for the estimation of proteins using either certain dyes which bind to specific groups of polypeptide side chains producing a protein dye colour complex, methods involving copper binding to peptide bonds or application of an eosin B red dye. In this study, an on-line automated technique based on the Lowry method has been used to estimate total protein output from the isolated lacrimal segments. This method can also be used to estimate total protein from saliva, or any other biological fluid, tissue homogenates or secretory tissues. The on-line automated method for the estimation of total protein from secretory tissues and biological fluid was designed mainly to obtain a rapid, simple and consistent graphical interpretation of result within 40-50 min of starting the experiment. The original chart recording of the time-course response can also be used for publication purposes. With this method, it is possible to investigate the effect of electrical field stimulation on the intrinsic secretomotor nerves employing either wire or platinum electrodes embedded in the perfusing chamber. Moreover, the tissue can also be stimulated with different concentrations of either drugs, hormones or neurotransmitters for different time periods. This method can also be combined with morphology whereby the stimulated tissue can be processed for neuropeptide or neurotransmitter immunohistochemistry to determine which neurotransmitters or neuropeptides are involved in the physiological responses. The automated method is simple and rapid and moreover, it can estimate accurately and directly at physiological pH small amount (ng-microgram) of proteins in effluent samples depending on the sensitivity of the chart recorder. In this study, neuropeptides and neurotransmitters were used as secretagogues in addition to electrical field stimulation. PMID- 9974143 TI - Markers for neuronal degeneration in organotypic slice cultures. AB - This protocol describes ways of monitoring spontaneous or induced neuronal degeneration in organotypic brain slice cultures. Hippocampal cultures (4-week old) are grown in normal serum-free control medium, or exposed to the neurotoxin trimethyltin (TMT) (0.5-100 microM) for 24 h or the excitotoxic glutamate agonist kainic acid (KA) (5-25 microM) for 48 h followed by 24 h or 48 h, respectively, in normal medium. Corticostriatal slice cultures (also 4-week-old) are exposed to KA (6-24 microM) for 48 h and normal medium for control. The resulting neurodegeneration is estimated by (a) propidium iodide (PI) uptake, (b) lactate dehydrogenase (LDH) efflux to the culture medium, (c) ordinary Nissl cell staining, (d) staining by the neurodegenerative marker Fluoro-Jade (FJ), (e) neuronal microtubule degeneration by immunohistochemical staining for microtubule associated protein 2 (MAP2), and (f) Timm sulphide silver staining for heavy metal alterations. Both hippocampal and corticostriatal slice cultures show a dose- and time-dependent increase in PI uptake and LDH efflux after exposure to TMT and KA. The mean PI uptake and the LDH efflux into the medium correlate well for both types of cultures. Both TMT and KA exposed hippocampal cultures display in vivo patterns of differential neuronal vulnerability as evidenced by PI uptake, FJ staining and MAP2 immunostaining. Corticostriatal slice cultures exposed to a high dose of KA display extensive striatal and cortical degeneration in FJ staining as suggested by a high PI uptake. A change in Timm sulphide silver staining in deep central parts of some control cultures, corresponds to areas with loss of cells in cell staining, loss of MAP2 staining, PI uptake, and FJ staining. We conclude that organotypic brain slice cultures, in combination with appropriate markers in standardized protocols, represent feasible means for studies of excitotoxic and neurotoxic compounds. PMID- 9974144 TI - Differentiating condition-induced facilitation, inhibition and disinhibition in a complex series of reflexes in an electromyogram. AB - In man, the principal exteroceptive reflexes evoked by intra-oral stimulation involve the jaw-closing muscles and include inhibitory and excitatory responses [H.W. van der Glas, A. De Laat, D. van Steenberghe, Oral pressure receptors mediate a series of inhibitory and excitatory periods in the masseteric post stimulus EMG complex following tapping of a tooth in man, Brain Res. 337 (1985) 117-125.]. These reflexes can be observed in electromyograms (EMGs) recorded with bipolar surface electrodes. The likelihood that these reflexes play important roles in the integrative actions of the jaw has led to interest in the physiological control mechanisms by which they may be modulated. It has been reported recently that the complex series of jaw reflexes evoked by non-painful tapping on human teeth can be modulated by the application of noxious stimulation to the hand [S.W. Cadden, H.W. van der Glas, F. Lobbezoo, A. van der Bilt, Effects of remote noxious stimulation on exteroceptive reflexes in human jaw closing muscles, Brain Res. 726 (1996) 189-197.] or by exercises which produce a change in mental state [S.W. Cadden, H.W. van der Glas, F. Lobbezoo, A. van der Bilt, The influence of attentional factors on short- and long-latency jaw reflexes in man, Arch. Oral Biol. 41 (1996) 995-998.]. The effects of remote noxious stimuli and mental exercises usually involved transient increases in electromyographic (EMG) activity around the interfaces between the successive inhibitory and excitatory reflexes. As the mechanisms underlying the tap-induced inhibitory and excitatory reflexes may show some temporal overlap [H.W. van der Glas, A. De Laat, D. van Steenberghe, Oral pressure receptors mediate a series of inhibitory and excitatory periods in the masseteric post-stimulus EMG complex following tapping of a tooth in man, Brain Res. 337 (1985) 117-125.], these condition-induced increases in EMG activity could, in the simplest hypothesis, have been due to either (i) a condition-induced inhibition of the tap-induced inhibitory influences on the motoneurones (i.e., disinhibition) and/or (ii) a condition-induced facilitation of the tap-induced excitatory influences underlying the subsequent excitatory reflexes. In the present protocol, we describe how it is possible to differentiate between these different underlying mechanisms. The method includes a regression analysis of the relationship between condition-induced changes in amplitude of a reflex and the reflex amplitude under control conditions after taking account of the effect of chance. The analysis is applied on reflex data pooled from various subjects. Although this method of data analysis is illustrated with trigeminal reflexes, it is potentially of use for other complex extracellular recordings including those in other fields of motor control (e.g., EMGs from muscles other than jaw ones). PMID- 9974145 TI - Serial sectioning of thick tissue with a novel vibrating blade microtome. AB - Vibrating blade microtomes are used extensively in biological research to section non-frozen tissue. There are a wide variety of commercial instruments available for this purpose, however, they are designed to cut thin sections primarily from a tissue block less than one centimeter in height. Herein is described a simple modification of a microscope frame that creates a vibrating blade microtome capable of producing a sequential series of sections through three centimeters of tissue. We illustrate the use of this device to identify and reconstruct a column of rat spinal motor neurons retrogradely labeled from a peripheral muscle. PMID- 9974146 TI - A technique for 125I-labelling of neurotrophins and the use of retrograde axonal transport as a bioassay. AB - The protocol presented here details a technique which enables the neurotrophins nerve growth factor (NGF), neurotrophin-3 (NT-3), neurotrophin-4 (NT-4), and brain-derived neurotrophic factor (BDNF) to be labelled using 125I and the bioactivity of these labelled proteins determined using an in vivo bioassay. We have found that the simplest and most effective method for 125I-labelling of neurotrophic factors is the IODO-GEN method. Following the iodination of neurotrophins it must be established that the labelling procedure has not affected the biological activity of the protein. Traditional methods of assaying the bioactivity of 125I-labelled neurotrophins have several disadvantages and a much easier protocol to use is the retrograde axonal transport of these proteins in sympathetic and sensory neurons of adult mice. High specific activity 125I labelled neurotrophin, to which known amounts of unlabelled neurotrophin are added, is injected into the right anterior eye chamber of adult mice under anaesthetic and the animals are left to recover for 16 h, after which they are sacrificed and both superior cervical ganglia (SCG) and trigeminal ganglia (TGG) are removed. The accumulated radioactivity in each ganglion is determined using a gamma-counter and the amount of neurotrophin transported is calculated by subtracting the counts obtained on the non-injected side from those present on the injected side. By comparing the amount of protein injected with the amount transported, the specific activity of the bioactive labelled neurotrophin can be determined. PMID- 9974147 TI - Intracellular filling and reconstruction of identified neurons in fixed rat brain slices. AB - A simple technique for the morphological characterization of pre-labelled neurons in fixed brain slices is described. Neurons are retrogradely-labeled with a carbocyanine dye and the tissue is fixed and sliced. Individual labeled cells from the interior of a slice are then visualized on an upright fluorescence microscope and impaled with a micropipet containing rhodamine or fluorescein peroxidase conjugates. The cells are filled by iontophoresis, postfixed, and the peroxidase is oxidized into a permanent, opaque reaction product. The dendritic morphology of the neurons is then reconstructed under camera lucida and quantified. PMID- 9974148 TI - The partner preference paradigm: a method to study sexual motivation and performance of female rats. AB - Sexual behavior of the female rat consists of initiative, as well as receptive components. Previous studies on female sexual behavior have focused on the reflexive response to a male's mount, i.e., the lordosis reflex, whereas the initiative and soliciting gestures that are exhibited by the female during copulation were ignored by most researchers. This bias led to a misconception of the female's role in the sexual act, according to which the female is passive and submissive, whereas the male rat is sexually dominant or even aggressive. In this paper, we describe a procedure, the partner preference paradigm, designed to investigate and quantify sexual motivation, initiation and solicitation in female rats. In this paradigm, the female can control the sexual act because the mobility of her sexual partner is limited. This setting enables to measure a variety of soliciting behaviors that reflect the active seeking of sexual contact by an estrous female. In addition, this paradigm enables the evaluation of the females' motivation to engage in a sexual act, by measuring the preference for a sexually appropriate over an indifferent partner. Moreover, the partner preference paradigm may be easily adopted for studies in male subjects, allowing the comparison of males' and females' responses to various experimental conditions. PMID- 9974149 TI - An evaluation of the role of mitochondria in neurodegenerative diseases: mitochondrial mutations and oxidative pathology, protective nuclear responses, and cell death in neurodegeneration. AB - There is mounting evidence for mitochondrial involvement in neurodegenerative diseases including Alzheimer's and Parkinson's disease and amyotrophic lateral sclerosis. Mitochondrial DNA mutations, whether inherited or acquired, lead to impaired electron transport chain (ETC) functioning. Impaired electron transport, in turn, leads to decreased ATP production, formation of damaging free-radicals, and altered calcium handling. These toxic consequences of ETC dysfunction lead to further mitochondrial damage including oxidation of mitochondrial DNA, proteins, and lipids, and opening of the mitochondrial permeability transition pore, an event linked to cell death in numerous model systems. Although protective nuclear responses such as antioxidant enzymes and bcl-2 may be induced to combat these pathological changes, such a vicious cycle of increasing oxidative damage may insidiously damage neurons over a period of years, eventually leading to neuronal cell death. This hypothesis, a synthesis of the mitochondrial mutations and oxidative stress hypotheses of neurodegeneration, is readily tested experimentally, and clearly points out many potential therapeutic targets for preventing or ameliorating these diseases. PMID- 9974150 TI - The planum temporale: a systematic, quantitative review of its structural, functional and clinical significance. AB - The planum temporale (PT) is a triangular area situated on the superior temporal gyrus (STG), which has enjoyed a resurgence of interest across several disciplines, including neurology, psychiatry and psychology. Traditionally, the planum is thought to be larger on the left side of the brain in the majority of normal subjects [N. Geschwind, W. Levitsky, Human brain: left-right asymmetries in temporal speech regions, Science 161 (1968) 186-87.]. It coincides with part of Wernicke's area and it is believed to consist cytoarchitectonically of secondary auditory cortex. Consequently, it has long been thought to be intimately involved in language function. The PT is, therefore, of relevance to disorders where language function is impaired, such as schizophrenia and dyslexia. The gross anatomical boundaries remain in dispute, and only recently has its cytoarchitecture begun to be studied again after 60 years silence, and finally its functional significance is only now being explored. In the first part of this review the structural aspects and anatomical boundaries of the PT in the normal brain from post mortem and magnetic resonance imaging (MRI) and methods of measurement are discussed. In the second part, studies of the functional significance of the PT in the normal brain are reviewed critically. Finally a meta-analysis of MRI measurements of the distribution of planum anatomy in normal subjects is presented. Comparison is made with clinical populations, including schizophrenia and dyslexia, and the influence of handedness and gender on such measurements is quantified. Although there are many ways of defining and measuring the PT with a wide variety of results, overall there is a significant leftward asymmetry in normals, which is reduced in left handers and females. The leftward asymmetry is much reduced in patients with schizophrenia due to a relatively larger right PT than normal controls. The review is intended to guide future researchers in this area. PMID- 9974151 TI - Branching and/or collateral projections of spinal dorsal horn neurons. AB - Branching and/or collateral projections of spinal dorsal horn neurons is a common phenomenon. Evidence is presented for the existence of STTm/STTl, STTc/STTi, STT/SMT, STT/SRT, SCT/DCPS, SST/DCPS, SCT/SST, STT/SHT, STeT/SHT, STeTs and other doubly or multiply projecting spinal neurons that have been anatomically and physiologically identified and named based on the locations of the cells of origin and their terminations in the brain. These newly discovered spinal projection neurons are characterized by a single cell body and branched axons and/or collaterals that project to two or more target areas in the brain. These novel populations of neurons seem to be a fuzzy set of spinal projection neurons that function as an intersection set of the corresponding single projection spinal neurons and to be at an intermediate stage phylogenetically. Identification strategies are discussed, and general concluding remarks are made in this review. PMID- 9974152 TI - Metabotropic glutamate receptors: electrophysiological properties and role in plasticity. AB - Electrophysiological research on mGluRs is now very extensive, and it is clear that activation of mGluRs results in a large number of diverse cellular actions. Studies of mGluRs and on ionic channels has clearly demonstrated that mGluR activation has a widespread and potent inhibitory action on both voltage-gated Ca2+ channels and K+ channels. Inhibition of N-type Ca2+ channels, and inhibition of Ca(++)-dependent K+ current, IAHP, and IM being particularly prominent. Potentiation of activation of both Ca2+ and K+ channels has also been observed, although less prominently than inhibition, but mGluR-mediated activation of non selective cationic channels is widespread. In a small number of studies, generation of an mGluR-mediated slow excitatory postsynaptic potential has been demonstrated as a consequence of the effect of mGluR activation on ion channels, such as activation of a non-selective cationic channels. Although certain mGluR modulation of channels is a consequence of direct G-protein-linked action, for example, inhibition of Ca2+ channels, many other effects occur as a result of activation of intracellular messenger pathways, but at present, little progress has been made on the identification of the messengers. The field of study of the involvement of mGluRs in synaptic plasticity is very large. Evidence for the involvement of mGluRs in one form of LTD induction in the cerebellum and hippocampus is now particularly impressive. However, the role of mGluRs in LTP induction continues to be a source of dispute, and resolution of the question of the exact involvement of mGluRs in the induction of LTP will have to await the production of more selective ligands and of selective gene knockouts. PMID- 9974153 TI - Amyotrophic lateral sclerosis associated with mutations in superoxide dismutase: a putative mechanism of degeneration. AB - Amyotrophic lateral sclerosis (ALS) is a devastating neurologic disease that rapidly progresses from mild motor symptoms to severe motor paralysis and premature death. Until recently, there were few substantive studies conducted on the pathogenesis of the disease. With the genetic linkage of mutations in the superoxide dismutase (SOD-1) gene with familial ALS patients, new avenues for study have become available including transgenic mice and culture models. Although not yet providing a complete picture of the disease mechanism, studies utilizing these model systems have greatly advanced our understanding of the mechanism of degeneration and should eventually lead to putative therapeutic agents. In this review, we will present the important findings from these model systems, provide a framework in which to evaluate these findings, and speculate on the mechanism of degeneration initiated by the mutations in SOD-1. PMID- 9974154 TI - Mu- and delta-opioid receptor densities in respiratory-related brainstem regions of neonatal swine. AB - The piglet displays similar postnatal development in respiration and sleep-wake behavior to the human. To shed light on the possible influence of opioid systems on these functions, this study assessed the density of mu- and delta-opioid receptors in brainstems of 2-3 and 5-7 (young), 14-17 (intermediate) and 20-21 (older) day-old piglets, using quantitative autoradiography. Serial 10 microns sections from fresh-frozen brains were incubated with either mu-(125I-DAGO) or delta-(125I-DPDPE) opioid ligands. The binding characteristics of each receptor remained unchanged over the age-range studied. delta-opioid receptor density was minimal in the young piglets, and increased over the age-range studied in all brainstem regions. mu-opioid receptor density exceeded delta-opioid density in all brainstem regions in young and older piglets, and remained unchanged with age. We conclude that, as in other species, the development of delta-opioid receptors in swine lags behind that of mu-opioid receptors, and that the distribution of each in the piglet's brainstem is distinct. The present findings help explain the changing influence of the mu- and delta-opioid systems on breating and state during postnatal development. PMID- 9974155 TI - Ontogeny of rolipram-sensitive, low-K(m), cyclic AMP-specific phosphodiesterase in rat brain. AB - The postnatal development of rolipram-sensitive, low-K(m), cyclic AMP-specific phosphodiesterase (PDE4) was investigated in discrete regions of rat brain using a PDE4 activity assay and immunoblot analyses with K116, a PDE4 antibody. The Vmax for cyclic AMP hydrolysis by PDE4 was lower at birth when compared to adult levels in cerebral cortex, cerebellum, and neostriatum. K(m) values for cyclic AMP hydrolysis by PDE4, in contrast, did not change throughout the observed period in any brain region tested. The developmental patterns for PDE4 were significantly different among the examined brain regions. PDE4 activity in olfactory bulb and hippocampus also was found to be lower at birth in comparison to adult levels. Immunoblot analyses showed that developmental patterns of PDE4 were significantly different for the various subtypes, and also varied substantially across brain regions. The results suggest that PDE4 might be differentially regulated by different ontogenetic events. PMID- 9974156 TI - Change of expression of full-length and truncated TrkBs in the developing monkey central nervous system. AB - We examined the expression of full-length TrkB (TrkBTK+) and truncated TrkB (TrkBTK-) in the central nervous system (CNS) of the macaque monkey (Macaca fascicularis) using a western blot analysis. At the adult stage, the levels of TrkBTK+ in cerebral cortices were higher than those in other structures of CNS and the expressions of TrkBTK+ in the association cortices (except area PE) were relatively lower than those in the primary cortices. In contrast, TrkBTK- in the hippocampus and the cerebellum was significantly higher than in other structures. In various developing cerebral cortices, TrkBTK+ was detected at the same levels from embryonic day 120 (E120) to the adult period. In contrast, the expression of TrkBTK- increased remarkably after the newborn stage (NB), reached the maximum level at postnatal day 60 (P60) and maintained the same level into adulthood. The peaks of TrkBTK- in the association cortices were more delayed than in the primary cortices. The expression of TrkBTK- occurred at a time that correlates with the elimination of axons and the down-regulation of neuropeptides. The present study suggests that TrkBTK- plays an important role in the axonal remodelling and that it may act as a negative effector of TrkBTK+ in the primate CNS, reducing responsiveness to BDNF and/or NT-4/5. PMID- 9974157 TI - Changes in mRNA levels for group I metabotropic glutamate receptors following in utero hypoxia-ischemia. AB - The expression of group I metabotropic glutamate receptors (mGluR1 and mGluR5) and inositol 1,4,5-trisphosphate receptor type 1 (IP3R1) mRNA was studied by in situ hybridization in the developing rat hippocampus after in utero hypoxia ischemia. In utero hypoxia-ischemia was induced by clamping the uterine blood vessels of near-term fetuses for 10 min. Fetuses were delivered surgically, resuscitated and raised by foster mothers until postnatal day 7 and 14. Results indicated a temporal delay in the expression of mGluR1 mRNA in the dentate gyrus of the ischemic animals. The mGluR1 mRNA level was significantly lower in the ischemic animals at postnatal day 7, but reached a similar level as that of controls at postnatal day 14. In utero hypoxia-ischemia did not change the temporal-spatial expression pattern of either mGluR5 or IP3R1 mRNA in the hippocampus. Between postnatal day 7 and 14, mGluR5 mRNA showed a high and relatively constant expression, whereas IP3R1 mRNA levels were increased in all regions examined. The differences in the expressions of group I mGluRs indicate that these receptors may have different functions during hippocampal development and may play different roles in excitotoxicity. PMID- 9974158 TI - Distribution and developmental changes in metabotropic glutamate receptor messenger RNA expression in the rat lumbar spinal cord. AB - Using in situ hybridisation, the regional distribution of primary transcripts and splice variants of all metabotropic glutamate receptor subtypes (mGluR) currently known to be expressed in the spinal cord have been studied in the lumbar enlargement of the rat spinal cord. In adult animals, the messenger RNA of the mGluR subtypes 1, 5, 3, 4 and 7 were differentially expressed. The transcripts of mGluR1 and 5 were most abundant with mGluR5 messenger RNA being concentrated in the superficial dorsal horn. In contrast, the mGluR2 transcript was not detectable with the sensitivity of the method. Secondly, age related changes (postnatal days 1, 7, 12, 21) in the postnatal expression of mGluR1-5 and 7 transcripts have been investigated. mGluR1 and 7 messenger RNA showed a general decrease in spinal expression from postnatal day 1 to day 21. Quantitative densitometry showed high mGluR3 and 5 messenger RNA levels especially in the superficial dorsal horn at birth, however these levels decreased with age. In addition to changes in density, the regional distribution of mGluR3 messenger RNA was altered with postnatal development. Up to postnatal day 12, mGluR3 messenger RNA expression was almost exclusively restricted to the spinal grey matter, but with postnatal day 21 a strong additional expression in the white matter occurred. Distribution of mGluR4 messenger RNA showed little change in the dorsal horn, however motoneuronal expression emerged during development. These changes may suggest different roles for mGluRs in the maturation of spinal transmission of the rat nervous system. PMID- 9974159 TI - Maturation of visual receptive field properties in the rat superior colliculus. AB - Visually responsive neurons were recorded in the superficial layers of rat superior colliculus from postnatal day 12 to 28. Receptive field properties such as size, type (ON, OFF, ON-OFF and motion sensitive) and direction selectivity were analyzed to disclose changes during maturation. Although some aspects of sensory properties are modified during development (latency, receptive field sizes, and proportions of receptive field types), a high level of sophistication is also present in young animals even before eyelid opening. For instance, direction selective and direction biased cells, which require complex synaptic relations, are already observed when the first light evoked responses emerge in the superior colliculus (P13), strongly suggesting that this property develops without visual experience. Furthermore, direction selectivity is present in the colliculus prior to the appearance of visually evoked activity in the cortex. This indicates that direction selectivity can not be attributable to incoming cortical afferents. This study provides the first direct evidence that, unlike the cat, the rat's cortico-tectal pathway is only weakly involved in the establishment of direction selectivity in collicular neurons. PMID- 9974160 TI - Developmental plasticity of ascending spinal axons studies using the North American opossum, Didelphis virginiana. AB - The objectives of the present study were to determine if axons of all ascending tracts grow through the lesion after transection of the thoracic spinal cord during development in the North American opossum, and if so, whether they reach regions of the brain they normally innervate. Opossum pups were subjected to transection of the mid-thoracic cord at PD5, PD8, PD12, PD20, or PD26 and injections of Fast Blue (FB) into the lower thoracic or upper lumbar cord 30-40 days or 6 months later. In the PD5 transected cases, labeled axons were present in all of the supraspinal areas labeled by comparable injections in unlesioned, age-matched controls. In the experimental cases, however, labeled axons appeared to be fewer in number and in some areas more restricted in location than in the controls. When lesions were made at PD8, labeled axons were present in the brain of animals allowed to survive 30-40 days prior to FB injections but they were not observed in those allowed to survive 6 months. When lesions were made at PD12 or later, labeled axons were never found rostral to the lesion. It appears, therefore, that axons of all ascending spinal pathways grow though the lesion after transection of the thoracic cord in developing opossums and that they innervate appropriate areas of the brain. Interestingly, the critical period for such growth is shorter than that for most descending axons, suggesting that factors which influence loss of developmental plasticity are not the same for all axons. PMID- 9974161 TI - Development of O4+/O1- immunopanned pro-oligodendroglia in vitro. AB - In this study, O4+/O1- pro-oligodendroglia isolated by immunopanning from cerebral hemispheres of P3-P5 rats were evaluated during their maturation in culture. Immunopanning yielded 3-4 x 10(5) cells/cerebrum, with 98% O4+ and 6% O1+. There was heterogeneity in the morphologies of immunopanned cells ranging from simple bipolar cells to more complex multipolar cells. As a first step in determining potential differentiative responses of mature oligodendroglia, we examined glial fibrillary acidic protein (GFAP) expression in response to fetal bovine serum (FBS) by cultures established from O4+/O1- immunopanned cells grown for 1, 14, or 21 days, exposed to 20% FBS for 6-7 days and fixed and immunostained on days 7, 21 or 28 in culture (DIC). When immunopanned cells were exposed to FBS following 1 day in serum-free medium, 88% expressed GFAP and when immunopanned cells were cultured for 14 days prior to FBS exposure, 78% expressed GFAP. By contrast, when cells were cultured for 21 days prior to FBS exposure (when a majority of the cells expressed O1 and myelin basic protein (MBP)), only 19% of the cells expressed GFAP (p < 0.001). Cells that were O4+/GFAP- even in the presence of FBS often exhibited a mature oligodendroglial morphology. Among immunopanned cells that responded to FBS by expression of GFAP, both process bearing (similar to type 2 astroglia) and flattened, polygonal (similar to type 1 astroglia) GFAP+ cells were observed. These results confirm the utility of immunopanning for the isolation of pro-oligodendroglia and demonstrate that oligodendroglia that develop in vitro from O4+/O1- immunopanned cells become resistant to GFAP induction by FBS. PMID- 9974162 TI - Regional distribution of cerebral blood volume and cerebral blood flow in newborn piglets--effect of hypoxia/hypercapnia. AB - The relationship between regional parenchymal cerebral blood volume (CBV), regional cerebral blood flow (CBF) and the calculated mean transit time (MTT) was investigated in 14 newborn piglets. The effects of combined hypoxic hypoxia (PaO2 = 32 +/- 5 mm Hg) and hypercapnia (paCO2 = 68 +/- 5 mm Hg) were measured in seven animals. Remaining animals served as the control group. During baseline conditions the highest CBF and CVB values were found in the lower brainstem and cerebellum, whereas white matter exhibited the lowest values (p < 0.05). MTT was prolonged within the cerebral cortex (2.34 +/- 0.42 s-1) compared with the thalamic MTT (1.53 +/- 0.38 s-1) (p < 0.05). Under moderate hypoxia/hypercapnia, a CBF increase to the forebrain (p < 0.05) resulted in an elevated brain oxygen delivery (p < 0.05) and so CMRO2 remained unchanged. Moreover, a moderate increase of CBV and a marked shortening of MTT occurred (p < 0.05). The CBV increase was higher in structures with lowest baseline values, i.e., thalamus (66% increase) and white matter (62% increase) (p < 0.05). MTT was between 22% of baseline in the lower brainstem and 49% in white matter (p < 0.05). We conclude that under normoxic and normocapnic conditions the newborn piglets exhibit a comparatively enlarged intraparenchymal CBV. Moderate hypoxia and hypercapnia induced a marked increase in cerebral blood flow which appears to be caused by an increased perfusion velocity, expressed by a strongly reduced mean transit time and by a concomitant CBV increase. PMID- 9974163 TI - Neurotrophic factors BDNF and GDNF protect embryonic chick spinal cord motoneurons from ethanol neurotoxicity in vivo. AB - Maternal consumption of ethanol is widely recognized as a leading cause of mental and physical deficits. Many populations of the central nervous system are affected by the teratogenic effects of ethanol. Neurotrophic factors (NTFs) have been shown to protect against ethanol neurotoxicity in culture, although there have been no demonstrations of such protection in vivo, in specific neuronal populations. Previous studies have demonstrated that ethanol is toxic to developing chick embryo motoneurons when administered from embryonic day 10 (E10) to E15. NTFs such as brain-derived neurotrophic factor (BDNF) and glial cell line derived neurotrophic factor (GDNF) have been shown to support developing spinal cord motoneurons, and when exogenously applied, decrease naturally occurring cell death, and protect against axotomy. The concurrent delivery of BDNF or GDNF with ethanol to the embryonic chick from E10 to E15 was designed to examine the capacity of these NTFs to provide in vivo neuroprotection for this ethanol sensitive motoneuron population. Analysis of motoneuron numbers indicated that both BDNF and GDNF provided protection to developing spinal cord motoneurons from ethanol toxicity, restoring motoneuron numbers to control levels. This study represents the first demonstration of in vivo neuroprotection from ethanol toxicity with respect to specific neuronal populations. PMID- 9974164 TI - Delayed neuronal loss after administration of intracerebroventricular kainic acid to preweanling rats. AB - Excitotoxins, such as kainic acid (KA), have been shown to produce both immediate and delayed neuronal degeneration in adult rat brain. While preweanling rats have been shown to be resistant to the immediate neurotoxicity of KA, the presence of delayed neuronal loss has not been investigated in such animals. To determine whether intracerebroventricular (i.c.v.) administration of KA would produce delayed neuronal loss, preweanling rats were administered 5 nmol or 10 nmol KA i.c.v. on postnatal day 7 (P7) and then examined at P14, P45, and P75. Using three-dimensional, non-biased cell counting, neuronal loss was observed in the CA3 subfield of the hippocampal formation at P45 and P75 in animals administered 10 nmol KA, as compared to animals administered 5 nmol KA or artificial cerebrospinal fluid. Further, the amount of immunoreactivity to jun, the protein product of the immediate early gene, c-jun, adjusted for the number of remaining neurons was increased in the same brain areas. Antibody labeling of inducible heat shock protein and glial fibrillary acidic protein was not similarly increased in animals administered i.c.v. KA. The data suggest that while i.c.v. KA does not produce immediate neuronal loss in preweanling rats, the hippocampus is altered so that neuronal loss occurs after a delay, perhaps through apoptosis. These findings may be relevant to the pathogenesis of neuropsychiatric disorders, such as schizophrenia, that are characterized by early limbic-cortical deficits but onset of illness in young adulthood. PMID- 9974165 TI - Neuronal activity influences the growth of barrels in developing rat primary somatosensory cortex without affecting the expression pattern of four major GABAA receptor alpha subunits. AB - Thalamic innervation plays a major role in parcellation of neocortex and maturation of cortical circuits. While the underlying mechanisms are unknown, lesion studies have identified GABAA receptors in neocortex as molecular targets of thalamic regulation [J. Paysan, A. Kossel, J. Bolz, J.M. Fritschy, Area specific regulation of gamma-aminobutyric acid A receptor subtypes by thalamic afferents in developing rat neocortex, Proc. Natl. Acad. Sci. USA 94 (1997) 6995 7000]. To determine the factors regulating the expression of GABAA receptors, the overall level of neuronal activity was chronically modulated in neonatal rat cortex. Slices of Elvax polymer loaded with the N-methyl-D-asparate (NMDA) receptor antagonist MK-801 or with brain derived neurotrophic factor (BDNF) were placed unilaterally over the left parietal cortex in newborn animals. Unlike thalamic lesions (Paysan et al., 1997), these chronic drug treatments did not alter the laminar distribution or the expression level of the four major GABAA receptor alpha subunit isoforms (alpha 1, alpha 2, alpha 3, alpha 5) in primary somatosensory cortex (S1), as assessed immunohistochemically after one week. In particular, the staining of the barrel field in layers III-IV, which is very prominent with the alpha 1-subunit, was preserved in the drug-treated hemisphere. Even systemic administration of MK-801 at birth, which resulted in pronounced retardation of cortical development, had no effect on the laminar distribution and staining intensity of the four GABAA receptor alpha subunit variants. However, the size of barrels in S1, as measured in tangential sections stained for the GABAA receptor alpha 1 subunit, was enlarged upon chronic, topical blockade of NMDA receptors with MK-801 and was reduced to the same extent upon chronic exposure to BDNF. Thus, these pharmacological treatments modulated cortical growth, possibly by exerting opposite effects on neuronal activity in S1. The results suggest that the parcellation of somatosensory cortex and the laminar distribution of GABAA receptor subtypes are governed primarily by factors independent of thalamocortical activity. PMID- 9974166 TI - Apoptosis in early ocular morphogenesis in the mouse. AB - Development of the eye requires complex interactions between tissues, extracellular matrix and growth factors. Most cells of the optic primordia grow and differentiate into discrete ocular structures; however, other cells have death as their developmental fate. The most common mechanisms of cell death are apoptosis and necrosis. We have identified the cell death that occurs during ocular morphogenesis in ZRDCT-N mice as apoptosis. Mouse embryos, ages E8.5 E11.5, were embedded in paraffin, sectioned at 5 microns and stained with hematoxylin or by the terminal deoxytransferase-mediated dUTP-biotin nick end labeling (TUNEL) method. The spatial and temporal distribution of apoptotic cells was mapped at 0.5 day intervals using a computerized image analysis system, and 3 D reconstructions were made at each embryonic age. Our data indicate that apoptosis plays a role in normal ocular morphogenesis and provides the groundwork for studies of abnormal ocular development. PMID- 9974167 TI - Naltrindole administration during the preweanling period and manipulation affect adrenocortical reactivity in young rats. AB - The effect of a daily injection of the delta-selective opioid antagonist naltrindole (1 mg/kg), from birth to postnatal day 19, on basal and post-stress corticosterone levels in 25-day old rats of both sexes was investigated. The effects of manipulation were studied by including two control groups, one group received daily injections of saline and a second one was not manipulated. The stress protocol consisted of a 3 min swimming session in water at 20 degrees C. Corticosterone determinations were performed by radioimmunoassay. Control non manipulated animals showed a significant increase in corticosterone levels in response to stress. Manipulation decreased basal hormone levels in females and prevented the stress-induced rise in corticosterone in males. Functional blockade of the delta-receptor during the preweanling period by the naltrindole treatment inhibited the corticosterone response to stress in females. The results indicate the existence of sex differences in the effects of manipulation on hypothalamus pituitary-adrenal axis activity and the involvement of the delta-opioid receptor in the modulation of the adrenocortical response to stress during the postnatal period. PMID- 9974168 TI - Pentylenetetrazol seizures induce cell suffering but not death in the immature rat brain. AB - To investigate whether long-term functional consequences of status epilepticus (SE) induced by pentylenetetrazol in 10-day-old rats correlated with cell injury and/or death, acid fuchsin and TUNEL staining were performed between 4 to 144 h after SE. Acid fuchsin stained hippocampus, amygdala and cerebral cortex at 24 h but not at 72 and 144 h. No DNA fragmentation was apparent at any time. Thus, immature neurons subjected to sustained seizures suffer transiently but survive probably by activating repair processes. PMID- 9974169 TI - The maturation of corticocollicular neurons in mice. AB - The location and development of the neurons that give rise to the corticocollicular projection were studied in C57BL/6J and 129SV/CPorJ anophthalmic mice. The first neurons that project to the superior colliculus appear in the subplate zone at E13 in C57BL/6J mice. Cortical plate neurons reach the colliculus about 2 days later. The appearance and development of these neurons are delayed by about 2 days in the anophthalmic strain. PMID- 9974170 TI - Bcl-2 and Bax expression following methylazoxymethanol acetate-induced apoptosis in the external granule cell layer of the developing rat cerebellum. AB - Since Bcl-2 protects a variety of cell types from programmed cell death, whereas Bax promotes apoptosis, the present study examines Bcl-2 and Bax proteins, and bcl-2 and bax mRNA expression in the developing cerebellum of the rat following methylazoxymethanol (MAM) acetate administration by using immunohistochemistry, Western blotting and Northern blotting. Bcl-2 expression in the developing cerebellum is observed in proliferating and differentiating cells, whereas Bax expression is higher in differentiating cells than in proliferating cells during development. Administration of MAM (0.05 microliter/g, i.p.) at postnatal day 3 produces apoptotic cell death, as detected by the characteristic morphology and positivity with the method of in situ end-labeling of nuclear DNA fragmentation of dying cells, in the external granule cell layer of the cerebellum. Dying cells are not stained with Bcl-2 and Bax antibodies. Furthermore, no modification in the intensity of Bcl-2 and Bax protein bands and in the intensity of Bcl-2 and bax mRNA bands on Western and Northern blots, respectively, were observed between control and treated rats. These data indicate that MAM-induced apoptosis is not associated with modifications in the expression of Bcl-2 and Bax. PMID- 9974171 TI - Differential sensitivity of tachykinin vs. enkephalin gene expression in the posterior striatum in response to acute p-chloroamphetamine treatment during postnatal development. AB - The acute effects of the monoamine releaser p-chloroamphetamine (pCA, 10 mg/kg, i.p.) on preprotachykinin (PPT) and preproenkephalin (PPE) mRNA expression in the anterior (A-STR) vs. posterior (P-STR) striatum were studied in rodents at postnatal days (PND) 10, 21 and 35. Northern analysis 4 h post-injection yielded no significant mRNA changes within the A-STR of any pCA group. However, significant increases (80-200% of saline control) in PPT mRNA levels occurred within the P-STR at all three postnatal ages. Interestingly, pCA did not increase PPE mRNA levels within the P-STR until PND 35 (150% of saline control). Such observation suggests that tachykinin neurons of the P-STR achieve an earlier monoamine-responsive signal transduction linkage to gene regulation as compared to enkephalin neurons. Given its predominance in the caudal regions of the striatum, 5-HT neurotransmission at the 5-HT2 receptor is suggested to play a central role in this mechanism. PMID- 9974172 TI - The neurobiology of cannabinoid transmission: from anandamide signaling to higher cerebral functions and disease. PMID- 9974174 TI - The CB1 cannabinoid receptor in the brain. AB - The CB1 cannabinoid receptor in brain is a G-protein-coupled receptor that exists as a protein possessing seven transmembrane helices that span the membrane. The intracellular surface is able to interact with f1p4oteins of the Gi/o family to regulate effector proteins, including adenylate cyclase, Ca2+ channels, and K+ channels, and to stimulate the mitogen-activated protein kinase pathway. The CB1 cannabinoid receptor recognizes three classes of agonist ligands: cannabinoid, eicosanoid, and aminoalkylindole. These agonist subtypes may interact with the CB1 cannabinoid receptor by some common points of association, yet may have subtle differences in the way that they interact with the receptor protein. This may be evident in the allosteric regulation by monovalent cations and individual agonists. The juxtamembrane region of the C-terminal is able to activate G proteins. It is proposed that conformational changes in the receptor induced by agonist ligands may alter the conformation or exposure of the juxtamembrane C terminal region extending from helix VII. PMID- 9974173 TI - Biochemistry of the endogenous ligands of cannabinoid receptors. AB - In 1992 the discovery of the first endogenous ligand of cannabinoid receptors, anandamide, provided conclusive support to the hypothesis that an "endogenous cannabinoid regulatory system" exists in mammalian nervous tissue. Anandamide (N arachidonoyl-ethanolamine) was the first of a series of long-chain fatty acid derivatives, including two other polyunsaturated N-acylethanolamines and 2 arachidonoyl-glycerol, found to exert cannabimimetic properties in either central or peripheral tissues. Here we review the current knowledge on the biochemical bases of the formation and inactivation of endogenous cannabinoid ligands as well as of their interaction with cannabinoid receptor subtypes. PMID- 9974175 TI - The functional neuroanatomy of brain cannabinoid receptors. AB - The effects of the primary psychoactive constituent of marijuana, delta 9 tetrahydrocannabinol, are mediated by cannabinoid receptors, CB1 and CB2. The CB1 receptors display a unique central nervous system (CNS) distribution and are present in mammalian brain at higher levels than most other known G-protein coupled receptors. The highest levels occur in several areas involved in motor control and hippocampus. Cannabinoid effects on CNS activities, including movement, memory, nociception, endocrine regulation, thermoregulation, sensory perception, cognitive functions, and mood, correlate with the regional distribution of cannabinoid receptors and their activation of specific G-protein mediated signal transduction systems in various brain regions. PMID- 9974176 TI - Function of cannabinoid receptors in the neuroendocrine regulation of hormone secretion. AB - Marijuana and its cannabinoid constituents have profound effects on anterior pituitary hormone secretion. Exposure to delta 9-tetrahydrocannabinol inhibits gonadotropin, prolactin, growth hormone, and thyroid-stimulating hormone release and stimulates the release of corticotropin. Consequently, cannabinoid exposure could have profound effects on the function of the reproductive system, lactation, metabolism, and on the endocrine stress axis. The acute effects of cannabinoids on the endocrine system are consistent with its actions on brain neurotransmitter systems involved in the regulation of neuropeptides that modulate anterior pituitary hormone secretion. Although cannabinoid receptors appear to play a major role in the ability of cannabinoids to influence hormone release, much remains to be learned concerning their function in the neuroendocrine regulation of hormone secretion. PMID- 9974177 TI - Cannabinoid transmission and pain perception. AB - The use of cannabis for the management of a wide range of painful disorders has been well documented in case reports throughout history. However, clinical evaluations of cannabis and its psychoactive constituent THC have not led to a consensus regarding their analgesic effectiveness. On the other hand, THC and its synthetic derivatives have been shown to be effective in most animal models of pain. These antinociceptive effects are mediated through cannabinoid receptors in the brain that in turn appear to interact with noradrenergic and kappa opioid systems in the spinal cord to modulate the perception of painful stimuli. The endogenous ligand, anandamide, is also an effective antinociceptive agent. The extent to which the endogenous cannabinoid system is involved in the modulation of pain is currently unknown. PMID- 9974178 TI - Endogenous cannabinoid signaling. PMID- 9974179 TI - Role of cannabinoid receptors in memory storage. AB - Studies have shown that delta 9-tetrahydrocannabinol, the principal psychoactive ingredient in marijuana, produces memory deficits similar to those produced by neurochemical lesions of the hippocampus. Such lesions impair performance in short-term spatial memory tasks learned prior to the lesion. Animals trained in the behavioral task following the lesion can still perform the task, but learn a different behavioral strategy. Cannabinoid agonists impair behavioral performance in a delay-dependent manner similar to that produced by lesions, but also shift the behavioral response strategy. A possible role for cannabinoid receptors and endogenous cannabinoids may thus be to regulate the storage (i.e., encoding) of information, as well as the means by which that information is retrieved. PMID- 9974180 TI - Role of the endogenous cannabinoid system in the regulation of motor activity. AB - One of the prominent pharmacological features of drugs acting at the brain cannabinoid receptor (CB1) is the induction of alterations in motor behavior. Catalepsy, immobility, ataxia, or the impairment of complex behavioral acts are observed after acute administration of either natural and synthetic cannabinoid receptor agonists or the endogenous CB1 ligand anandamide. The dense presence of CB1 receptors in the cerebellum and in the basal ganglia, especially at the outflow nuclei (substantia nigra and the internal segment of the globus pallidus), supports the existence of an endogenous cannabinoid system regulating motor activity. In the basal ganglia, the functionality of the anandamide-CB1 system is poorly understood. Dual effects are often observed after the administration of CB1 ligands in animal models of pharmacological manipulation of basal ganglia transmitter systems, indicating that the activity of the anandamide CB1 system depends on the ongoing activation of the different elements of the basal ganglia. This finding is in agreement with the proposed activity-dependent release of anandamide from a plasmalemma precursor. Additionally, a potential state-dependent bidirectional coupling of the CB1 receptor to the adenylate cyclase transduction system has also been described. From this perspective, the endogenous cannabinoid system can be proposed as a local regulator of neurotransmission processes within the basal ganglia. This system may serve as a counterregulatory homeostatic mechanism preserving the functional role of basal ganglia circuits in coding the serial order of events that constitute movement. PMID- 9974181 TI - Cannabinoid transmission and reward-related events. AB - The reward/reinforcement circuitry of the mammalian brain consists of synaptically interconnected neurons associated with the medial forebrain bundle, linking the ventral tegmental area, nucleus accumbens, and ventral pallidum. Electrical stimulation of this circuit supports intense self-stimulation in animals and, in humans, produces intense pleasure or euphoria. This circuit is strongly implicated in the neural substrates of drug addiction and in such addiction-related phenomena as withdrawal dysphoria and craving. This circuit is also implicated in the pleasures produced by natural rewards (e.g., food, sex). Cannabinoids are euphorigenic in humans and have addictive liability in vulnerable persons, but were long considered "anomalous" drugs of abuse, lacking pharmacological interaction with these brain reward substrates. It is now clear, however, that cannabinoids activate these brain substrates and influence reward related behaviors. From these actions, presumably, derive both the abuse potential of cannabinoids and the possible clinical efficacy in dysphoric states. PMID- 9974182 TI - Brain cannabinoid systems as targets for the therapy of neurological disorders. AB - Unprecedented developments in cannabinoid research within the past decade include discovery of a brain (CB1) and peripheral (CB2) receptor; endogenous ligands, anandamide, and 2-arachidonylglycerol; cannabinoid drug-induced partial and inverse agonism at CB1 receptors, antagonism of NMDA receptors and glutamate, and antioxidant activity; and preferential CB1 receptor localization in areas subserving spasticity, pain, abnormal involuntary movements, seizures, and amnesia. These endogenous structures and chemicals and mechanisms are potentially new pathophysiologic substrates, and targets for novel cannabinoid treatments, of several neurological disorders. PMID- 9974183 TI - The role of nitric oxide in digoxin-induced arrhythmias in guinea-pigs. AB - We have investigated the effects of nitric oxide synthase inhibitor (L-NAME), nitric oxide precursor (L-arginine) and nitric oxide donor (sodium nitroprusside) on digoxin-induced arrhythmias both in guinea-pig isolated hearts and in anaesthetised animals. Sodium nitroprusside (0.1 mumol kg-1 min.-1 for 70 min.) caused a marked inhibition in mortality and arrhythmia score but L-NAME (10 mg kg 1) and L-arginine (30 mg kg-1 intravenous bolus followed by 10 mg kg-1 min.-1 for 60 min.) treatments were ineffective in anaesthetised guinea-pigs. None of the drugs markedly affected the time of onset of first arrhythmias or ventricular fibrillation incidence. In isolated heart experiments, nitric oxide generated by either L-arginine (1 mM) or sodium nitroprusside (1 mM) significantly reduced the arrhythmia score whereas L-NAME (1 mM) had no effect. Ventricular fibrillation incidence was totally abolished by sodium nitroprusside and none of the hearts treated with L-arginine had an irreversible ventricular fibrillation. L-NAME decreased ventricular tachycardia duration but increased ventricular fibrillation duration. There were no marked changes in the time of onset of first arrhythmias with these drugs in in vitro experiments. These results suggest that nitric oxide may play a modulatory role in the digoxin-induced arrhythmias in guinea-pigs. PMID- 9974185 TI - Induction of hepatic CYP2B in foetal and neonatal rats after maternal administration of phenobarbital. AB - We examined hepatic cytochrome P450 (CYP) induction in rat foetuses and neonates by phenobarbital administered through placenta or breast feeding. In an intraperitoneal study, phenobarbital was administered intraperitoneally to mother rats once a day for 7 consecutive days before delivery. The livers were removed from foetuses, neonates, and mothers just before and 5 and 10 days after delivery. In oral administration study, water containing phenobarbital was given orally ad libitum from day 13 of pregnancy to 3 weeks after delivery (end of lactation). The livers were removed from neonates and mothers just before and one week after delactation. Phenobarbital administered intraperitoneally increased both the activity and the protein expression of CYP2B in 5-day-old neonates, even though the administration ended before delivery. This increase had disappeared in 10-day-old neonates. In mother rats, phenobarbital increased CYP2B just before and 5 days after delivery, while no increase was detected 10 days after delivery. Phenobarbital administered orally also increased both the activity and the protein expression of CYP2B of neonates and mothers during lactation and this increase also disappeared 1 week after delactation. Neither activity nor protein expression of CYP3A were induced in perinates at any age examined in either administration route. In mother rats, increase in CYP3A was found only just before delivery in the peritoneal administration study. Our results suggest that phenobarbital administered through placenta or breast milk transiently induces hepatic CYP2B in newborn rats but that the influence of phenobarbital does not last long. PMID- 9974184 TI - Long-term changes in brain following continuous phencyclidine administration: an autoradiographic study using flunitrazepam, ketanserin, mazindol, quinuclidinyl benzilate, piperidyl-3,4-3H(N)-TCP, and AMPA receptor ligands. AB - Phencyclidine induces a model psychosis which can persist for prolonged periods and presents a strong drug model of schizophrenia. When given continuously for several days to rats, phencyclidine and other N-methyl-D-aspartate (NMDA) antagonists induce neural degeneration in a variety of limbic structures, including retrosplenial cortex, hippocampus, septohippocampal projections, and piriform cortex. In an attempt to further clarify the mechanisms underlying these degeneration patterns, autoradiographic studies using a variety of receptor ligands were conducted in animals 21 days after an identical dosage of the continuous phencyclidine administration employed in the previous degeneration studies. The results indicated enduring alterations in a number of receptors: these included decreased piperidyl-3,4-3H(N)-TCP (TCP), flunitrazepam, and mazindol binding in many of the limbic regions in which degeneration has been reported previously. Quinuclidinyl benzilate and (AMPA) binding were decreased in anterior cingulate and piriform cortex, and in accumbens and striatum. Piperidyl 3,4-3H(N)-TCP binding was decreased in most hippocampal regions. Many of these long-term alterations would not have been predicted by prior studies of the neurotoxic effects of continuous phencyclidine, and these results do not suggest a unitary source for the neurotoxicity. Whereas retrosplenial cortex, the structure which degenerates earliest, showed minimal alterations, some of the most consistent, long term alterations were in structures which evidence no immediate signs of neural degeneration, such as anterior cingulate cortex and caudate nucleus. In these structures, some of the receptor changes appeared to develop gradually (they were not present immediately after cessation of drug administration), and thus were perhaps due to changed input from regions evidencing neurotoxicity. Some of these findings, particularly in anterior cingulate, may have implications for models of schizophrenia. PMID- 9974186 TI - Pharmacokinetics of bisphosphonates in rabbits. AB - Clodronate, pamidronate and etidronate are commonly used bisphosphonates, which accumulate extensively in arteries and some other tissues. We compared their pharmacokinetics in rabbits with those of tiludronate, the drug newly introduced to clinical use. The 14C-labelled drugs were given intravenously and plasma drug levels were monitored for up to 24 hr. The dose-related plasma concentrations of tiludronate and etidronate were clearly higher and decreased more slowly than those of clodronate and pamidronate (P < 0.001). Already at 5 min., the concentrations of tiludronate and etidronate were higher than those of clodronate and pamidronate (P = 0.016). At 24 hr, plasma concentration of tiludronate was 12 +/- 6.6%, of etidronate 18 +/- 2.5%, of clodronate 0.8 +/- 0.2%, and of pamidronate 1.4 +/- 0.4% of the dose per body weight. With the same dose (25 mg/kg), absolute AUC0-24 hr for tiludronate and etidronate was 9-11 times larger than for clodronate. AUC0-24 hr for pamidronate (2.5 mg/kg) was 11% of that for clodronate. Plasma clearance of tiludronate and etidronate was 9-15 times slower than that of clodronate and pamidronate. At 24 hr, the mean tissue-to-plasma ratio of tiludronate for aorta was 1.2-1.6. For bone, spleen, liver and kidneys the ratio varied from 5.4 to 52.6. The results suggest that 1) tiludronate and etidronate are removed from plasma much slower than clodronate and pamidronate, and 2) the potential of tiludronate to concentrate in arteries and bone is generally smaller than previously found with the other bisphosphonates. PMID- 9974187 TI - Tizanidine protects mice against convulsions induced by lidocaine: involvement of alpha 2-adrenoceptors. AB - The effects of alpha-adrenoceptors agents on seizures induced by intraperitoneal administration of lidocaine (75 mg/kg) were studied in mice. Pretreatment with the selective alpha 2-adrenoceptor agonist, tizanidine, decreased the incidence of seizures induced by lidocaine. Tizanidine increased the latency to the first seizure in those animals which progressed to seizures. The blockade of alpha 2 adrenoceptors with yohimbine or phentolamine counteracted the protection induced by tizanidine. The selective alpha 2-adrenoceptor antagonist, prazosin, did not modify the protection induced by tizanidine. The alpha 2-adrenoceptor agonist clonidine also increased the latency to the first seizure induced by lidocaine. The protective effect of clonidine was also reversed by pretreatment with the selective alpha 2-adrenoceptor antagonist yohimbine. Taken together, these results suggest that alpha 2-adrenoceptors are involved in seizures induced by lidocaine. PMID- 9974188 TI - The rat Subcutaneous Air Sac model: a quantitative assay of antiangiogenesis in induced vessels. AB - A new in vivo experimental model--the Subcutaneous Air Sac (SAS) model-has recently been presented to replace a previous in vivo rabbit cornea assay where neovascularisation was induced by chemical injury of the cornea or by implantation of tumour cells intracorneally, a methodology which is believed to cause severe pain to the animals. In the SAS model, an air sac is induced by injection of air subcutaneously on the back of the animal. After 10-14 days the air sac appears as an almost transparent avascular membrane in which induction of new vessels can be studied. We present recent developments of this technique: In the SAS-tumour technique, vascular endothelial growth factor-producing tumour cells are inoculated subcutaneously directly on the membrane, and the formation of new vessels is measured 8 days later. In the SAS-pellet technique, slow release pellets containing angiogenic factors, basic fibroblast growth factor or vascular endothelial growth factor are implanted on the subcutaneous membrane by a simple operation. The formation of new vessels is measured 10 days later. The ability of the SAS-tumour- and SAS-pellet techniques to detect an antiangiogenic effect of a systemically administered compound was investigated using the fumagillin analogue TNP-470 (o-chloroacetyl-carbamoyl)-fumagillol) as a positive control given subcutaneously for 7 and 9 days, respectively. At a dose of 10 mg TNP-470/kg/day the angiogenesis was reduced by approximately 70% in the SAS tumour technique and by 40-60% in the SAS-pellet technique. The animals were unaffected by the SAS methodology. The SAS-tumour and SAS-pellet models are considered complementary and make use of simple and almost similar techniques which facilitate the evaluation. PMID- 9974189 TI - A comparison of the efficacy of acetylcholinesterase reactivators against cyclohexyl methylphosphonofluoridate (GF agent) by in vitro and in vivo methods. AB - The purpose of this study was to compare the therapeutic efficacy of a new acetylcholinesterase reactivator, designated BI-6 (1-(2 hydroxyiminomethylpyridinium)-4-(4-carbamoylpyridinium )-2-butene dibromide), with presently used oximes (pralidoxime, obidoxime, methoxime) and H-oximes (HI 6, HLo-7) by in vitro and in vivo methods. In vitro, methoxime seems to be the most efficacious reactivator of GF agent-inhibited acetylcholinesterase because the phosphorylation of acetylcholinesterase by GF agent markedly increases its affinity for the enzyme. The oxime BI-6 is more efficacious than other presently used oximes (pralidoxime, obidoxime) but its reactivating efficacy does not reach the efficacy of H-oximes tested. On the other hand, obidoxime and pralidoxime appear to be very poor reactivators of GF agent-inhibited acetylcholinesterase because the phosphonylation of acetylcholinesterase by GF agent markedly decreases their affinity to the enzyme. In vivo, H oximes (HI-6, HLo-7) are the most efficacious antidotes for the treatment of acute poisoning with GF agent in rats while the presently used oximes such as pralidoxime and obidoxime are practically ineffective. BI-6 and methoxime are more efficacious than pralidoxime and obidoxime, nevertheless their therapeutic efficacy does not reach the efficacy of H oximes. Our results show that the ability of oximes to reactivate GF agent-inhibited acetylcholinesterase in vitro usually corresponds to their therapeutic effects against GF agent in vivo. PMID- 9974190 TI - Cholecystokinin receptor mechanism(s) and morphine tolerance in mice. AB - In a previous work, the effects of cholecystokinin receptor agonists on tolerance to morphine antinociception were evaluated. In the present study, the influence of cholecystokinin antagonists on the inhibition of tolerance to morphine antinociception by cholecystokinin agonists has been investigated. Maximum tolerance to morphine antinociception was obtained by morphine administration (50 mg/kg) to mice once daily for 4 days. The cholecystokinin receptor agonists caerulein (0.005 mg/kg) or cholecystokinin-8 (0.01 mg/kg) but not unsulfated cholecystokinin-8 (0.01 mg/kg) decreased the development of tolerance to morphine (9 mg/kg). The cholecystokininA receptor antagonist MK-329 (1 mg/kg) or the cholecystokininB receptor antagonist L-365,260 (0.25, 0.5 and 1 mg/kg) also diminished the tolerance to morphine antinociception. When animals were challenged with different doses of MK-329 (0.25, 0.5 and 1 mg/kg) against cholecystokinin-8 (0.01 mg/kg), caerulein (0.005 mg/kg) or unsulfated cholecystokinin-8 (0.01 mg/kg) on day 4 in tolerant mice, different response were obtained. Higher doses of MK-329 (1 mg/kg) caused a small decrease in attenuation of the morphine tolerance induced by cholecystokinin-8 and caerulein. Low doses of L-365, 260 diminished the effect of cholecystokinin-8 on morphine tolerance. Conversely high doses of the drug potentiated the response of caerulein (0.005 mg/kg). When animals were treated with MK-329 or L-365,260 before unsulfated cholecystokinin-8, reduction of the tolerance to morphine antinociception was obtained. These data indicate that both cholecystokinin receptors may modulate morphine tolerance. PMID- 9974191 TI - Exercise and organ transplantation. AB - Life-saving treatment of disease by organ transplantation has become increasingly important. Annually over 35,000 transplantations of vital organs are carried out world-wide and the demand for knowledge regarding exercise in daily life for transplant recipients is growing. The present review describes whole-body and organ reactions to both acute exercise and regular physical training in persons who have undergone heart, lung, liver, kidney, pancreas or bone marrow transplantation. In response to acute exercise, the majority of cardiovascular, hormonal and metabolic changes are maintained after transplantation. However, in heart transplant recipients organ denervation reduces the speed of heart rate increase in response to exercise. Furthermore, lack of sympathetic nerves to transplanted organs impairs the normal insulin and renin responses to exercise in pancreas and kidney transplant recipients, respectively. In contrast, surgical removal of sympathetic liver nerves does not inhibit hepatic glucose production during exercise, and denervation of the lungs does not impair the ability to increase ventilation during physical exertion. Most studies show that physical training results in an improved endurance and strength capacity in almost all groups of transplant recipients, which is of importance for their daily life. With a little precaution, organ transplant recipients can perform exercise and physical training and obtain effects comparable with those achieved in the healthy population of similar age. PMID- 9974192 TI - One-leg standing balance and sports activity. AB - The objective of the present cross-sectional study was to estimate one-leg standing balance in athletes and to investigate the relationship with type and amount of sports activity. The study comprised 339 active, competitive, non pregnant athletes, aged 14-24 years from two sports clubs in the county of Aarhus, Denmark. The athletes answered a questionnaire about occupation and sports activity. One-leg standing balance was measured as the maximum time of one legged balancing. The mean of the maximum time of one-legged balancing was 29 s (interquartile range 11.25-33.5 s). One-leg standing balance was positively associated with years of participation in basketball and was not associated with sex and age. We conclude that participation in basketball may induce significantly adaptive effects on standing balance. PMID- 9974193 TI - Motor performance in different dynamic tests in knee rehabilitation. AB - Functional dynamic tests are increasingly used in rehabilitation after injuries of the lower extremities. In these tests quantitative measures (e.g. time, height, distance) are mainly used as parameters, whereas the quality of the neuromuscular performance is poorly evaluated. In the present study the neuromuscular performance of leg muscles in different motor tasks was investigated 10-16 months after ACL-reconstruction. In 39 subjects with arthroscopically assisted ACL-reconstruction and 20 controls, isometric knee extensor strength, thigh circumference, knee stability, subjective knee function and the neuromuscular performance (by kinematic data and EMG) during three dynamic tests (stair descending, one-legged drop jump, one-legged cyclic hops) were measured. During the strength measurements a superimposed twitch technique was used for the detection of neuromuscular inhibition. The results demonstrate a significantly reduced Lysholm-Score and a distinct strength deficit, but no neuromuscular inhibition and no differences in knee stability in the operated leg. Besides reduced motor abilities of the injured leg, significant differences of the neuromuscular performance could be detected. It was evident that different test conditions revealed different persisting changes of the neuromuscular performance, which could not be detected by kinematic parameters alone. PMID- 9974194 TI - Supplement use and nutritional habits in Norwegian elite athletes. AB - The purpose of this study was to examine nutritional and supplemental habits among international alpine- and cross-country skiers and power sport athletes in Norway. Data from all the athletes of the National alpine skiing team (ALP; n = 33, 19 men and 14 women) and the National cross-country skiing team (CRO; n = 34, 17 men and 17 women) plus a mixed group of power sport athletes (POW: n = 33, all men) from the National teams of boxers, weightlifters and track and field athletes, were collected through a semi-structured interview during their annual medical examination. Twenty percent of all the athletes reported unsatisfactory nutritional habits (CRO 6%, ALP 27% and POW 27%; CRO vs. ALP/POW P < 0.05). Eight four percent used one or more micronutrient supplement (ALP 70%, POW 88%, CRO 95%; ALP vs. CRO/POW P < 0.01). Power sport athletes had the most frequent use of supplemental creatine (45%), proteins/amino acids (30%), vitamins (88%) and minerals (82%), and CRO had the most frequent intake of iron (94%), vitamin C (88%) and fish oils (91%). Among ALP, only 7% of the female athletes supplemented iron regularly compared to 37% of male ALP (P < 0.05) Overall, male athletes supplemented mostly on a regular basis and female athletes more on an occasional basis. The results show that in spite of differences between sport groups, many elite athletes report unsatisfactory nutritional habits. Micronutrient supplementation was prevalent, but varied between both groups of sports and gender. PMID- 9974195 TI - The effect of aerobic training in girls with idiopathic scoliosis. AB - The purpose of the present study was to investigate the effect of aerobic training in girls with idiopathic scoliosis, in selective respiratory parameters (VC, FVC, FEV1, FEV1/VC% FEV1/FVC) as well as the ability to perform aerobic work (PWC170). The training group consisted of 20 young girls with a mean age of 13.5 +/- 0.16 years. They wore a Boston-type brace for a mean period of 0.30 +/- 0.04 years and suffered from a scoliotic curve (27.4 +/- 1.9 degrees). They followed a two-month training program on the cycloergometer. Each training session lasted 30 min and was performed four times a week. The control group consisted of 20 girls with a mean age of 13.6 +/- 0.18 years and they wore the same type of brace for a mean period of 0.24 +/- 0.04 years. They also suffered from a scoliosis (29.5 +/- 1.8 degrees). The results of the study revealed that aerobic training sustained (VC, FEV1, FEV1/VC) or improved significantly (FVC, FEV1/FVC) the parameters of pulmonary function, while the respective parameters (VC, FVC) for the control group were reduced during the two-month period. The ability to perform aerobic work increased 48.1% (P < 0.01) in the training group, while it decreased 9.2% (P < 0.01) in the control group. PMID- 9974196 TI - Prevention of injuries in young female players in European team handball. A prospective intervention study. AB - Young female players in European handball have a very high injury incidence, up to 50 injuries per 1000 hours of game. More than half of these injuries happen without any external cause. The aim of the study was to investigate the effect of an intervention programme designed to reduce the number of injuries in young female players in European handball, with special emphasis on injuries in the lower extremities. The programme was created using elite athlete training programmes and those designed for rehabilitation of injured athletes with functional instability of their ankles and rupture of the anterior cruciate ligament. It included the use of an ankle disk for 10-15 min at all practice sessions, for one 10-month season (August 1995-May 1996). Twenty-two teams participated in the study, and were randomly assigned to the intervention or control group. Eleven teams with 111 players were randomised to the intervention group and 11 teams with 126 players to the control group. Data were analysed using a t-test for continuous variables, chi2-analysis and Fisher's exact test for dichotomous variables and multivariate methods to determine odds-ratios. The results indicated that using the intervention programme decreased the numbers of both traumatic and overuse injuries significantly. The differences in injuries between the groups were 80% during games and 71% during practice. In addition, the players in the control group had a 5.9 times higher risk of acquiring an injury than the players in the intervention group. PMID- 9974197 TI - Salmeterol and physical performance at -15 degrees C in highly trained nonasthmatic cross-country skiers. AB - The aim of this double-blind, placebo-controlled, cross-over study was to investigate possible improvement in physical performance at an ambient temperature of -15 degrees C by an inhaled dose of 50 micrograms salmeterol in 8 highly trained nonasthmatic cross-country skiers. FEV1 was measured before, during and after the treadmill exercise protocol, which consisted of a warm-up run, runs of 10 min at 90% and 5 min at 80% VO2max, followed by a timed run to exhaustion. Despite a significant improvement in FEV1, salmeterol did not have a beneficial effect on heart rate, blood lactate concentration, respiratory exchange ratio, oxygen uptake or minute ventilation during the exercise protocol. Running time to exhaustion was not significantly different from placebo. This lack of enhancement of exercise performance in healthy endurance athletes further supports the recent approval of salmeterol for prophylactic use by asthmatic athletes during training and competition. PMID- 9974198 TI - Eye injuries in sports. AB - In a retrospective study from 1988 to 1998, eye injuries were found in 553 patients. Seventy-six (13.7%) of these injuries were associated with sport. The mechanism of trauma was for the most part a ball (71.1%) or a club (13.2%). Most eye injuries occurred in soccer (35.5%), which is, by far, the most widespread sport in this region of Norway. A disproportionately high number of the injuries occurred in floorball (17.1%), bandy (13.2%), and squash (10.5%). The rules in these sports may, in theory, be strict enough to prevent eye injuries in most cases. However, these rules are often neglected in informal activities. Strategies for educating the general public about the potentially serious effect of eye injuries in sports exposed to such risk are of great importance. PMID- 9974200 TI - Five-year outcome of 13 patients with an initially undiagnosed anterior cruciate ligament rupture. AB - We evaluated retrospectively the 5-year outcome of 13 patients with an initially undiagnosed and thus untreated anterior cruciate ligament rupture. At follow-up, these patients experienced decreased knee function and moderate to severe knee instability. They had attempted to reduce their discomfort by decreasing their activity level during the follow-up period. Immediately after the 5-year examination, 6 of the patients decided to have a late reconstruction of the ruptured anterior cruciate ligament. These results agree with previous reports of the natural course of anterior cruciate ligament ruptures. PMID- 9974199 TI - Calf muscle atrophy and Achilles tendon healing following experimental tendon division and surgery in rats. Comparison of postoperative immobilization of the muscle-tendon complex in relaxed and tensioned positions. AB - We used a rat model to study the effects of immobilization of the calf muscle tendon complex after an experimental Achilles tendon repair. Immobilizations of the complex in either a relaxed or tensioned position were compared by histochemical and morphometric analyses at the site of the tendon injury as well as in the gastrocnemius and soleus muscle bellies. The type of immobilization did not affect the healing of the tendon injury because no reruptures occurred in either of the treatment groups and the average tendon end-to-end distance did not differ between the groups. However, immobilization in a relaxed position led to a significantly more extensive fiber atrophy in the calf muscles. In clinical practice, these results suggest that rehabilitation after Achilles tendon surgery can be early and gradually tension- and load-increasing without a significant increase in the risk of rerupture of the tendon. PMID- 9974201 TI - Signs and symptoms of temporomandibular disorders in 19-year-old individuals who have undergone orthodontic treatment. AB - Fifty-five per cent of the 1554 19-year old subjects in Halmstad, Sweden, born in 1975, have received orthodontic treatment. Among these, 520 have been treated by specialists (specialist group) and 340 by general practitioners after consultation with specialists (consultation group). The aims were to study the prevalence of signs and symptoms of temporomandibular disorders (TMD) in these two groups on a long-term basis, to identify any possible difference between the groups, and to compare the results with those from a previously presented epidemiological study (control group). From the population of orthodontically treated subjects, a sample was randomly selected to represent the two groups, and 260 subjects agreed to attend for investigation, the participation rate being 77%. The investigation consisted of a questionnaire and clinical examination focusing on function and dysfunction of the masticatory system. Severe signs and symptoms of TMD were rare, the prevalence did not differ significantly between the two orthodontic groups, and the results were similar in the control group. The prevalence of several signs and symptoms was more common in females than in males. No significant correlation between TMD signs and symptoms and occlusal contact recordings was found. It was concluded that the vast majority of the 19 year old individuals who had undergone orthodontic treatment had well-functioning masticatory systems, and severe signs and symptoms of TMD were rare. PMID- 9974202 TI - Treatment of malocclusions in children and adolescents at a public dental service clinic in Sweden: extent and cost. AB - This study was undertaken to investigate the extent and the cost of orthodontic consultation and treatment of malocclusions in 19-year-olds at a Public Dental Service (PDS) clinic. A further aim was to evaluate the group of patients who discontinued their treatment prematurely. A total of 223 patient records were reviewed. The results showed that every second patient (106 of 223) was seen by a specialist for orthodontic evaluation. Of these, 54% (57 of 106) were treated with removable appliance, 29% (31 of 106) benefited from interceptive treatment without appliance and 12% (13 of 106) were referred to a specialist clinic. The costs for specialist consultations comprised 19% of the overall orthodontic treatment cost. Premature interruption of treatment with removable appliance was found in 17% (10 of 57) of the patients. This group consumed 12% of the overall orthodontic treatment cost. Reasons for discontinuing treatment included problems with co-operation and motivation and a lack of parental support. Seventy per cent of those who discontinued their treatment prematurely had been treated with an activator. PMID- 9974203 TI - A five-year evaluation of fissure sealants applied by dental assistants. AB - The aim of this study was to evaluate if sealings of fissures is a preventive method appropriate for delegation to auxiliary personnel. After a two-day course, giving theoretical as well as practical knowledge, 77 dental assistants working at twelve dental clinics, sealed 3218 first and second permanent molars in children. The material used was the light-cured resin Delton Opaque. The sealings were examined once a year by the childrens ordinary dentists, using internationally accepted criteria. The result showed a total retention rate of 91% after one year and 69% after five. There were differences in success rate between the clinics, the majority demonstrating a five-year total retention rate between 70 and 94%. It was evident that the retention of sealings was influenced by the age of the children but not by the position of teeth in the mouth. The main part of failures appeared during the first year (35%) and failures were essentially due to fractures (64%). Eight percent of all teeth present at the end of the five-year period had become carious. The dental assistants sealed the fissures without any assistance and none of them had any previous experience of fissure sealings. In our opinion, sealing of fissures is a method well suited for delegation to dental assistants after proper education but should be followed up, as the success rate showed a great variation. PMID- 9974204 TI - Dental survey at school with the purpose to select children with no actual need of dental treatment. AB - The purpose of this study was to develop an examination method to select children without from children with need of dental treatment. Furthermore the objective was that these examinations could be performed as a survey at school, without utilizing an expensive and fully equipped dental clinic but still maintain the certainty for the individual not to be at increased risk to be declared false caries-free, in comparison with ordinary examination at a dental clinic. The material comprised 88 children 10-13 years old. The children were subject to a survey-examination at school and a few weeks later at a dental clinic by the same examiner. Initially the children were examined at school by two examiners in order to measure the inter-examiner variability. The results showed that 2 of the 88 examined children (2.3%) were judged false healthy at school examination with respect to caries. The inter-examiner variability in diagnosing caries was greater than the intra-examiner variability between survey at school and examination at the dental clinic. PMID- 9974205 TI - Changes in Swedish dental health 1968-91. AB - Studies of changes in dental health are essential in discussions of national health policy matters. In the Level of Living Survey representative samples of the population aged 18-75 were interviewed in 1968, 1974, 1981, and 1991. In the 1991 survey those aged 76+ were also interviewed. Between all the four waves of the survey edentulousness and partial edentulousness decreased and the proportion of persons with teeth with many fillings, crowns or bridges increased. After 1974 the proportion of persons with teeth in good condition with few or no fillings also increased. The fall in edentulousness indicated a greater improvement in dental health than did the rise of the proportion of people with teeth in good condition. Age-specific comparisons showed that the change affected older people most. The largest fall in edentulousness and partial edentulousness was in ages above 50. This fall led to a nearly equal increase in the same ages of persons that had teeth with many fillings, crowns or bridges. This has meant that dental care needs have risen among older people in particular. The results are discussed in connection with the national dental health insurance scheme which was introduced in 1974. PMID- 9974206 TI - Financing the delivery of public-sector animal health services in Jamaica: pre- and post-privatization. AB - Lack of adequate financing was a major reason for the privatization of veterinary services in Jamaica in 1992. The belief was that, with privatization, funding of animal health services delivery would improve, since staff numbers and clinical activities undertaken by the Veterinary Division were reduced. However, analyses of data revealed that, in most cases, privatization neither improved nor stemmed the declines, that had started before privatization, in the measures or indicators used. It was concluded that privatization of veterinary services did not result in any appreciable improvement in the financing of the delivery of public-sector animal health services in Jamaica in the short term. PMID- 9974207 TI - Susceptibility to tropical theileriosis of calves born to dams immunized with Theileria annulata (Hisar) cell culture vaccine. AB - The susceptibility/immune status to tropical theileriosis of calves born of immunized dams was evaluated. Six cows were vaccinated with the Theileria annulata cell culture vaccine in the eighth month of pregnancy. Sera from the immunized dams exhibited very high post-vaccination antibody titres as determined by the indirect fluorescent antibody (IFA) test. The calves born to these dams did not show antibodies against T. annulata at the time of birth (IFA titres of < 1:20). The new-born calves were fed colostrum from their mothers and were challenged with T. annulata-infected ground tick supernate at 5-7 days of age. All the calves developed fever (from day 5-6 onwards) and parasitological reactions (from day 8-9 onwards) after challenge. There was a significant decrease in the haemoglobin and packed cell volume of the calves after challenge. All the calves showed signs of acute theileriosis by day 9-10 after challenge and had to be treated with buparvaquone in order to save their lives. The study indicated that detectable levels of anti-theilerial antibodies were not transferred from immune dams to their offspring. All the calves born to immunized dams were fully susceptible to theileriosis and thus themselves needed vaccination. PMID- 9974208 TI - Traditional livestock in semi-arid north eastern Zimbabwe: Mashona cattle. AB - Productivity data were gathered from Mashona cows (n = 187) in 28 traditionally managed herds in two areas, separated by a corridor 20-30 km wide of almost uninhabited bush in NE Zimbabwe. Cattle are kept primarily to provide oxen for work. Cows in the southern area, which had been more affected by drought in 1991 92, were younger (7.2 vs. 9.1 years) and had a longer median calving interval (548 vs. 406 days). Metrical data (n = 105 cows) showed these cattle to be larger bodied than those in the northern area (heart girth 146 vs. 144 cm). Market prices, estimated by respondents, were higher for oxen and herds were smaller in the south, and calf survival was believed by owners to be more influenced by season of birth in this area. Data were obtained on 531 calves. Before the age of 12 months 6.2% died, a low proportion compared with other studies. Most were retained in herds but 11.5% were slaughtered, sold or given away. All owners practised castration, selecting fast growing, strong bull calves for breeding. PMID- 9974209 TI - Incidence of gross reproductive abnormalities in small east African zebu cattle. AB - Reproductive organs from mature Small East African zebu (SEAZ) heifers and cows slaughtered at the Morogoro abattoir were collected twice a month and evaluated over a period of 12 months. Out of the 402 animals from which reproductive organs were taken, 54% were pregnant, 24% were actively cycling and 22% were non cycling. Various gross abnormalities were observed in the reproductive organs of about 16% of the cattle, and the major reproductive abnormality in both total and the non-cycling animals was various degrees of fibrous adhesion between the ovary and the infundibulum and mesosalpinx. It is concluded that, contrary to common belief, a majority of the female SEAZ cattle that are slaughtered are fertile. PMID- 9974210 TI - The effect of gonadotrophin releasing hormone and follicle stimulating hormone in conjunction with pregnant mare serum gonadotrophin on the superovulatory response in crossbred sheep in India. AB - Thirty-two mature crossbred (Fine Wool Synthetic, FWS) sheep developed for fine wool production in India were treated for superovulation and oestrus synchronization in spring season. The ewes were randomly allocated to four treatment groups in a factorially designed experiment. For induction of superovulation, pregnant mare serum gonadotrophin (PMSG) was administered alone (group 1), in combination with gonadotrophin releasing hormone (GnRH) (group 2) or with follicle stimulating hormone (FSH) (group 3) and with both (group 4). Oestrus was synchronized in all the ewes by two injections of prostaglandin F2 alpha (PGF, 10 mg each) administered at an interval of 10 days. Superovulation treatment started 48 h prior to the second PGF injection. The proportion of ewes in oestrus did not differ significantly (p > 0.05) in the four groups. The use of GnRH set the ewes into oestrus earlier than the ewes in the other groups. Treatment with PMSG (800 IU) in conjunction with 4 micrograms of Buserilin (GnRH) increased the ovulation rate (9.1 +/- 2.6 corpora lutea (CL)) above that observed when PMSG was used alone (3.0 +/- 0.7 CL). The use of FSH (0.5 U ovagen) in conjunction with PMSG was characterized by a decrease in the proportion of ewes with < or = 2 CL (4/8 vs 7/8; p < 0.05) and in the number of ovulations, i.e. CL observed (2.4 +/- 0.6 vs 9.1 +/- 2.6), and a nonsignificant increase in the incidence of large follicles (LF) (4.6 +/- 1.28 vs 3.25 +/- 0.6; p > 0.05). The interaction between treatments of FSH and GnRH was not significant (p > 0.05). It is concluded that use of GnRH, in conjunction with either PMSG alone or PMSG plus FSH treatment, advanced the onset of oestrus and increased the ovulation rate in FWS sheep. PMID- 9974211 TI - Decreased densities of intramembranous particles and cytochemically detectable cholesterol in microvilli of starved rat enterocytes. AB - The densities of intramembranous particles (IMPs) and of sterol complexes induced by treatment of filipin were studied by freeze-fracture replication of intact intestine and/or isolated brush border membranes (BBM) of well-fed and starved rats. The density of IMPs and filipin-sterol complexes (FSCs) decrease considerably during starvation. Biochemical estimations show a decrease in the levels of cholesterol and proteins with respect to phospholipids during starvation which is in agreement with morphological findings. It is suggested that these changes may play a role in regulating membrane fluidity which in turn affects absorption of nutrients through BBM. PMID- 9974212 TI - Cell position-dependent reciprocal feedback regulation of type I collagen gene expression in cultured human skin fibroblasts. AB - In order to investigate possible cell positional effects on the gene expression of human dermal fibroblasts, the authors cultured the cells on non-coated polystyrene culture dishes, type I collagen-coated dishes, or collagen gels formed by type I collagen, or suspended them in type I collagen gels and measured collagen synthesis by the cells. The production rate of type I collagen was similar whether cells were cultured on non-coated polystyrene or on type I collagen-coated dishes, but it was suppressed significantly when the cells were placed within the collagen gel matrix. Time-dependent expression of genes for alpha 1 (I) and alpha 2 (I) collagen chains was measured by Northern blot analysis. A significant increase in mRNA levels for these chains was observed when the cells were cultured for three days on type I collagen-coated dishes or on collagen gels. On the other hand, a significant decrease in the mRNA levels was observed after 2 days and later, when the cells were cultured within type I collagen gel matrix. These results indicate that human dermal fibroblasts recognize their position on or in type I collagen (extracellular matrix) and respond by changing their expression patterns of type I collagen chain genes. The results of the kinetics of gene expression also suggest that upregulation and downregulation of type I collagen genes are controlled by different mechanisms. PMID- 9974213 TI - Localization and distribution of pituitary adenylate cyclase-activating polypeptide in the rat epididymis. AB - Previous investigation has provided evidence for the control of electrogenic chloride secretion by pituitary adenylate cyclase-activating polypeptide (PACAP) across the rat epididymal epithelium using electrophysiological measurement of transepithelial transport in cultured epididymal system. Hence, it suggests that epididymal and sperm functions are subject to control by a local PACAP system in the rat epididymis. In the present study, localization and distribution of PACAP in the rat epididymal duct was studied by an indirect immunofluorescence technique in conjunction with confocal laser scanning microscopy. Immunoreactivity for PACAP was found in all regions of the epididymal duct. However, the intensity of immunoreactivity for PACAP was stronger in the caput and corpus regions when compared to that of the cauda epididymidis. Much weaker immunostaining for PACAP, as compared to those found in other regions, was observed in the cauda epididymal tubules which are in close proximity to the vas deferens. No immunoreactivity for PACAP was found in epididymal spermatozoa. Together with the previous finding, the present results suggest that PACAP may exhibit a regional difference in its expression along the epididymal duct and it may act in a paracrine or autocrine fashion in the regulation of epididymal chloride secretion and hence fluid secretion, thus regulating epididymal and sperm functions along the epididymal duct. PMID- 9974214 TI - Localization of annexin VI in the adult and neonatal heart. AB - Annexins are a major family of intracellular Ca(2+)-binding proteins which have been implicated in a variety of cellular functions. In this paper the authors have used confocal microscopy to compare the distribution of annexin VI in vibratome sections of the rat adult left ventricle and striated muscle of the rat oesophagus. It is shown that in rat cardiac myocytes annexin VI is associated with only the sarcolemma and intercalated discs. In contrast, it is demonstrated that in rat skeletal muscle annexin VI is associated with the sarcoplasmic reticulum, in addition to the plasma membrane, suggesting that annexin VI is regulating different processes in these tissues. Also shown is that in vibratome sections of the neonatal rat left ventricle, annexin VI has a different subcellular location to that observed in the terminally differentiated adult myocyte. In these differentiating neonatal cells annexins VI is also associated with specific subcellular structures. Furthermore, using confocal microscopy of isolated myocytes the authors demonstrate that the association of annexin VI with the sarcolemma is stable even after cells are treated with the intracellular calcium chelator BAPTA-AM, to greatly deplete cytosolic calcium levels. This demonstrates that annexin VI associates tightly with the sarcolemma, and suggests that components in addition to phospholipid are involved in binding annexin VI to the membrane. These results demonstrate that the subcellular location of annexin VI is differentially regulated, and suggest that annexin VI is required for a process or processes characteristic of the sarcolemma, and of the sarcoplasmic reticulum of skeletal but not of heart muscle. PMID- 9974216 TI - Binding properties of bovine ocular lens zeta-crystallin to right-handed B-DNA, left-handed Z-DNA, and single-stranded DNA. AB - Bovine zeta-crystallin has the ability to bind with different DNAs. Initially, this protein was named regulatory factor 36 (Kang et al., 1985), but it has been shown to be an ocular lens zeta-crystallin (Jornvall et al., 1993), which is considered an enzyme-crystallin (Rodakanaki et al., 1989). The enzyme-linked immunosorbent assay (ELISA) was used to quantitate the binding of bovine zeta crystallin to purified high molecular weight double-stranded (ds-) and single stranded (ss-) DNA (bovine and synthetic DNA). ELISA quantitation was achieved by the addition of anti-zeta-crystallin antibodies to the DNA-zeta-crystallin complex, using a novel immunochemical avidin-biotin method. Zeta-crystallin shows much greater binding intensity for ss-DNA and for ds-Z-DNA than for ds-B-DNA. It also reacts slightly more with ds-Z-DNA than ss-DNA. Therefore, we speculate that zeta-crystallin may act as a transcriptional enhancer (outer lens cortex), possibly binding to Z-DNA regulatory elements within lens crystallin genes. It may also act to protect DNA from endogenous DNase activity and as a DNA unwinding (destabilizing) protein also involved with transcription, occurring in normal adult bovine lens nucleated secondary fiber cells. PMID- 9974215 TI - Modulation of osteogenic differentiation in human skeletal cells in Vitro by 5 azacytidine. AB - Cellular differentiation is controlled by a variety of factors including gene methylation, which represses particular genes as cell fate is determined. The incorporation of 5-azacytidine (5azaC) into DNA in vitro prevents methylation and thus can alter cellular differentiation pathways. Human bone marrow fibroblasts and MG63 cells treated with 5azaC were used as models of osteogenic progenitors and of a more mature osteoblast phenotype, respectively. The capacity for differentiation of these cells following treatment with glucocorticoids was investigated. 5azaC treatment led to significant expression of the osteoblastic marker alkaline phosphatase in MG63 osteosarcoma cells, which was further augmented by glucocorticoids; however, in human marrow fibroblasts alkaline phosphatase activity was only observed in glucocorticoid-treated cultures. MG63 cells represent a phenotype late in the osteogenic lineage in which demethylation is sufficient to induce alkaline phosphatase activity. Marrow fibroblasts are at an earlier stage of differentiation and require stimulation with glucocorticoids. In contrast, the expression of osteocalcin, an osteoblastic marker, was unaffected by 5azaC treatment, suggesting that regulation of expression of the osteocalcin gene does not involve methylation. These models provide novel approaches to the study of the control of differentiation in the marrow fibroblastic system. PMID- 9974217 TI - Alterations in distribution of actin binding proteins in uterine stromal cells during decidualization in the rat. AB - Immunohistochemistry was used to investigate the involvement of the actin associated binding proteins, tropomyosin, alpha-actinin and gelsolin with the formation of the decidual cell reaction during early pregnancy in the rat. Tropomyosin was present in the uterine myometrium, but absent from the both decidual and non-decidual stromal cells. alpha-Actinin was absent from non decidual stromal cells, but present in decidual cells. Gelsolin was present in non-decidual cells close to the uterine stroma as well as in transformed decidual cells. Both gelsolin and alpha-actinin were concentrated around the periphery of the cell. It is proposed that these actin-binding proteins may be involved with the cellular transformations associated with decidualization. PMID- 9974218 TI - The biostimulatory effect of red laser irradiation on pig blood platelet function. AB - The molecular mechanisms of laser-induced changes in the cell structure and function are not well known. The authors examined the effects of low-power laser irradiation on unnucleated pig blood platelets. The obtained results showed that laser irradiation (1-5 J) caused in blood platelets lipid peroxidation (measured as thiobarbituric acid reactive substances) and superoxide anion generation, concomitant with the release of adenine nucleotides and proteins from platelets. The maximum platelet response to laser irradiation was observed when doses of 1.8 2 J were used. Our results indicate that red laser irradiation induces: (1) platelet secretory process and the release of substances stored in the specific granules (adenine nucleotides, proteins); and (2) lipid peroxidation partly due to stimulation of endogenous arachidonate and production of its metabolites reacting with thiobarbituric acid. PMID- 9974219 TI - Enhancement of neutral trehalase activity by oxidative stress in the fission yeast Schizosaccharomyces pombe. AB - Addition of hydrogen peroxide, menadione, or plumbagin to growing cultures of the fission yeast Schizosaccharomyces pombe increased trehalase activity. The effect was inhibited only slightly in the presence of cycloheximide, indicating that the stimulation of trehalase triggered by oxidative stress is mostly due to posttranscriptional activation. Northern blot analysis of trehalase mRNA level revealed that oxidative stress also induces a moderate rise in transcription of trehalase. Mutants disrupted in genes encoding elements of the mitogen-activated protein kinase (MAPK) cascade showed a reduced increase in trehalase activity upon oxidative challenge, which was coincident with a block in transcription of trehalase. Taken together, the results support the idea that the enhancement of trehalase by oxidative stress is due to enzyme activation (via the Pka1/Sck1 phosphorylation pathway) and induction of trehalase mRNA (via the MAPK signaling pathway). In spite of the trehalase increase, a net accumulation of trehalose was noticed during the oxidative stress. PMID- 9974220 TI - The tbf-1 gene from the white truffle Tuber borchii codes for a structural cell wall protein specifically expressed in fruitbody. AB - This paper reports the purification and localization of a Tuber borchii Vittad, fruitbody protein (TBF-1) and the cloning of the encoding gene. TBF-1 is detectable by SDS-PAGE analyses only in this white truffle species and presents a molecular mass of 11,994 Da. TBF-1 was purified by one-step Reversed-Phase HPLC and its complete amino acid sequence was determined after digestion with trypsin and N-Asp endoproteinase. Polyclonal antibodies were produced and tested in immunofluorescence and immunogold experiments, providing information about the protein localization. It was detected mostly on the hyphal walls, where it was colocalized with beta-1,3-glucans and chitin. The sporal wall was not labeled. The encoding gene (tbf-1) was cloned using several techniques involving PCR. The coding region consists of a 360-bp open reading frame interrupted by an intron, with another intron following the stop codon. A putative signal peptide of 12 amino acids was found at the N-terminal. Northern blot analysis revealed that tbf 1 is highly expressed in unripe and ripe fruitbodies and was not detectable in culture mycelium or ectomycorrhizal roots. PMID- 9974221 TI - Recombinant glucoamylase production by Aspergillus niger B1 in chemostat and pH auxostat cultures. AB - The production of glucoamylase (GAM) by Aspergillus niger B1, a genetic transformant containing an additional 20 copies of the homologous glucoamylase gene (glaA) was studied in nutrient (maltodextrin)-limited chemostat and nutrient excess pH auxostat cultures. In these culture systems the specific production rate of GAM increased with dilution rate and reached a maximum (up to 15.0 mg GAM [g biomass]-1 h-1) when A. niger B1 was grown at its maximum specific growth rate in pH auxostat culture, indicating that GAM is a growth-associated product. The appearance of spontaneous morphological mutants was observed in all continuous flow cultures grown at pH 5.4, with a light brown mutant always displacing the parental strain. However, no morphological mutants were observed in cultures grown at pH 4.0. Further, when A. niger B1 was grown in pH auxostat culture, the specific production rate of GAM was 31% higher at pH 4.0 than at pH 5.4. Southern blot analyses showed that some morphological mutants (including the light brown mutant) isolated from a pH auxostat culture had lost copies of the glaA genes. PMID- 9974222 TI - Distribution of the fungal transposon Restless: full-length and truncated copies in closely related strains. AB - The fungal transposon Restless of Tolypocladium inflatum ATCC 34921 is a member of the hAT family of mobile DNA elements. In order to study the distribution of this transposon we have looked at 13 fungal strains, most of which are taxonomically related to strain ATCC 34921. Three strains, which show identical banding patterns in a comparative RAPD analysis with strain ATCC 34921, similarly carry multiple copies of Restless. In addition, 1 T. inflatum strain and 2 Beauveria nivea strains contain only a few or even single copies of the transposon. Inverse PCR and DNA sequencing analysis revealed that 1 strain contains a nonmobile truncated version of the element, while the other one harbors a full-length transposon copy which was named Restless-2. The presence of a single transposon copy of Restless in a defined Beauveria strain indicates recent acquisition of this transposon, since class II transposons usually occur in several copies per haploid genome. Notably, the corresponding genomic location is not occupied by a transposon copy in strain ATCC 34921. PMID- 9974223 TI - Lovastatin triggers an apoptosis-like cell death process in the fungus Mucor racemosus. AB - The filamentous dimorphic fungus Mucor racemosus possesses three ras genes, Mras1, 2, and 3, whose expression is correlated to morphogenesis of the fungus. Lovastatin, an indirect inhibitor of protein prenylation, altered the processing of MRas1 protein, blocked the accumulation of MRas3 protein, and caused the MRas1/p20 protein complex to disappear in M. racemosus. Concurrently it arrested sporangiospore germination, decreased growth rate, caused a loss of cell viability accompanied by cell shrinkage, increased cell density and cytoplasm condensation, and triggered DNA fragmentation, resulting in nucleosomes and nucleosome multimers. The specific morphological and biochemical events seen in Mucor cell death, particularly DNA fragmentation, resemble the best known characteristics of classical apoptosis in mammalian cells and prompted us to classify lovastatin-induced cell death as an apoptosis-like process. Lovastatin did not cause cell death in a leucine auxotroph of Mucor grown in YNB minimal medium, conditions which support only spherical growth during spore germination. Exogenous dibutyryl-cAMP initiated morphogenesis from hyphal (polar) growth to yeast-like (spherical) growth during spore germination and strongly prevented cell death which resulted from lovastatin treatment. Wortmannin added together with dibutyryl-cAMP showed a synergistic effect in the prevention of fungal cell death. These data suggest that the regulation of lovastatin-induced cell death in Mucor requires a signal transduction pathway(s) involving cAMP whose function is specific to a particular developmental stage. PMID- 9974224 TI - Health effects of microwave exposures: a review of the recent (1995-1998) literature. AB - Occupational or residential exposures to radio frequency radiation, including microwaves, have been alleged to result in health problems, including leukemia, other cancers, and reproductive mishaps. This review covers the recent literature (from 1995 to 1998) dealing with possible health effects, including original studies, reviews, commentaries, and editorials. A number of these articles have presented misconceptions, errors in citation, and inaccuracies regarding the alleged effects. Epidemiological reviews and studies dealing with exposures to radio frequency radiation from television transmitters, cellular telephones and towers, magnetic resonance imaging, phased array radar systems, and other occupational exposures are analyzed. On the basis of studies reported in the past several years, one can conclude that the evidence for any proven health effects of low-level microwave exposure is minimal to non-existent. PMID- 9974225 TI - Electron nuclear double resonance determined structures of enzyme reaction intermediates: structural evidence for substrate destabilization. AB - Angle selective ENDOR of nitroxyl spin-labels is briefly reviewed to illustrate the methodology of structure analysis developed in our laboratory for characterizing catalytically competent intermediates of enzyme catalyzed reactions. ENDOR structure determination of a reaction intermediate of alpha chymotrypsin formed with a kinetically specific spin-labeled substrate and of an enzyme-inhibitor complex formed with a spin-labeled transition-state inhibitor analog is briefly described. Both spin-labeled molecules bound in the active site of the enzyme are found in torsionally distorted conformations. It is suggested that this torsionally distorted state in which the bound ligand is of higher potential energy than in the ground state conformation reflects substrate destabilization in the course of the enzyme catalyzed reaction. PMID- 9974226 TI - Applications of electron paramagnetic resonance spectroscopy to study interactions of iron proteins in cells with nitric oxide. AB - Nitric oxide and species derived from it have a wide range of biological functions. Some applications of electron paramagnetic resonance (EPR) spectroscopy are reviewed, for observing nitrosyl species in biological systems. Nitrite has long been used as a food preservative owing to its bacteriostatic effect on spoilage bacteria. Nitrosyl complexes such as sodium nitroprusside, which are added experimentally as NO-generators, themselves produce paramagnetic nitrosyl species, which may be seen by EPR. We have used this to observe the effects of nitroprusside on clostridial cells. After growth in the presence of sublethal concentrations of nitroprusside, the cells show they have been converted into other, presumably less toxic, nitrosyl complexes such as (RS)2Fe(NO)2. Nitric oxide is cytotoxic, partly due to its effects on mitochondria. This is exploited in the destruction of cancer cells by the immune system. The targets include iron-sulfur proteins. It appears that species derived from nitric oxide such as peroxynitrite may be responsible. Addition of peroxynitrite to mitochondria led to depletion of the EPR-detectable iron-sulfur clusters. Paramagnetic complexes are formed in vivo from hemoglobin, in conditions such as experimental endotoxic shock. This has been used to follow the course of production of NO by macrophages. We have examined the effects of suppression of NO synthase using biopterin antagonists. Another method is to use an injected NO-trapping agent, Fe-diethyldithiocarbamate (Fe-DETC) to detect accumulated NO by EPR. In this way we have observed the effects of depletion of serum arginine by arginase. In brains from victims of Parkinson's disease, a nitrosyl species, identified as nitrosyl hemoglobin, has been observed in substantia nigra. This is an indication for the involvement of nitric oxide or a derived species in the damage to this organ. PMID- 9974227 TI - A point about electron paramagnetic resonance detection of irradiated foodstuffs. AB - This paper makes a point about the identification of irradiated foodstuffs by means of electron paramagnetic resonance (EPR) or electron spin resonance (ESR). EPR is the most accurate method for such routine applications since radicals are stabilised for a long time in all (or part of) foods that are in solid and dry states; consequently, EPR can be applied to meat and fish bones, fruit and relative products (from vegetal origin). More details are given for mollusc shells, such as oysters and mussels. PMID- 9974228 TI - The effect of automated compensation for incongruent axes on teleoperator performance. AB - Teleoperation is frequently performed with misalignments between operator or camera viewing direction and controller orientation. Examples of this occur in endoscopic surgery and in teleoperation with multiple camera views. The objective of this study was to find a method to automatically compensate for those misalignments so that human operators performing tasks under such scenarios could achieve levels of performance comparable to aligned conditions without additional training requirements. In this paper we report on a set of experiments conducted to test a method developed for that purpose. Participants were asked to track a randomly moving target on a computer display using a cursor controlled with a joystick. Performance was recorded under various visual-motor misalignments with and without automated compensation. Results indicated significant improvements in operator performance through use of automatic compensation only under certain types of misalignment. Actual or potential applications of this research include teleoperation and endoscopic surgery. PMID- 9974229 TI - Effects of display resolution on visual performance. AB - The role of display resolution in visual information processing was investigated in 2 experiments. Experiment 1 examined the effects of 2 CRT conditions (resolutions of 60 and 120 dots per inch [dpi]) and a paper control condition (255 dpi) on proofreading speed and accuracy. The results showed that reading performance was significantly better in the paper condition than in the 2 CRT conditions. Experiment 2 examined the effects of 3 different CRT resolutions (62, 69, and 89 dpi) on eye movement parameters (fixation duration and number of fixations) in a visual search task. Further, search reaction times (RTs) and observers' ratings of visual fatigue were analyzed. RTs and fixation durations were significantly increased in the low-resolution condition (62 dpi) as compared with the high-resolution condition (89 dpi). The significant interaction between display resolution and time both for search RTs and fixation durations was taken as evidence for stronger fatigue in the low-resolution conditions. Additionally, the extent of visual fatigue correlates both with search RTs and eye movement parameters. This finding gives rise to the assumption that observers' responsiveness to effects of display resolution in terms of visual fatigue differs markedly. Actual or potential applications of this research include recommendations for the use of high-resolution displays (90 dpi and greater) to optimize visual performance, to make prolonged on-screen viewing more comfortable, and to avoid visual fatigue. PMID- 9974230 TI - A comparison of seven visual fatigue assessment techniques in three data acquisition VDT tasks. AB - We compared 7 methods of measuring visual fatigue--accommodation power, visual acuity, pupil diameter, critical fusion frequency (CFF), eye movement velocity, subjective rating of visual fatigue, and task performance--for their sensitivity to visual load. In the experiment, 10 participants performed a monitoring task at 2 viewing distances, read articles under 2 levels of screen contrast, and tracked visual targets at 2 different speeds. The same measurement techniques, excluding pupil diameter and eye movement velocity, were compared by extending the task time from 20 to 60 min with the same VDT tasks to test for possible improvement in sensitivity. The results indicated that sensitivities of accommodation power, visual acuity, and CFF were greatly improved by a longer task period, but these 3 measurement techniques did not distinguish among tasks. Pupil diameter, eye movement velocity, and subjective rating of visual fatigue were sensitive in differentiating tracking from reading and monitoring tasks. Eye movement velocity and subjective rating were sensitive to the changes in target velocity of the tracking task. Although task performance was not directly comparable to other measurement techniques, it helped to ensure that participants maintained the same performance level by devoting more resources to the high-load conditions. Actual or potential applications of this research include using some of these assessment techniques for the design of adaptive displays. PMID- 9974231 TI - Context effects in subjective mental workload ratings. AB - The impact of performance context on subjective mental workload ratings was assessed with the Subjective Workload Assessment Technique (SWAT) and the NASA Task Load Index (TLX). In Experiment 1, a strong context effect was demonstrated. A low range of task difficulty produced considerably higher ratings on a common set of difficulty levels than did a high range of task difficulty. In Experiment 2, increasing the participants' range of experiences during practice eliminated the context effect. We recommend that methods for standardizing context, such as providing experience with the complete difficulty range, be developed for subjective mental workload evaluations. Actual or potential applications of this research include providing methodologies for controlling context effects in practical assessments of mental workload to increase the validity of subjective measures. PMID- 9974232 TI - Measures and interpretations of vigilance performance: evidence against the detection criterion. AB - Operators' performance in a vigilance task is often assumed to depend on their choice of a detection criterion. When the signal rate is low this criterion is set high, causing the hit and false alarm rates to be low. With increasing time on task the criterion presumably tends to increase even further, thereby further decreasing the hit and false alarm rates. Virtually all of the empirical evidence for this simple interpretation is based on estimates of the bias measure beta from signal detection theory. In this article, I describe a new approach to studying decision making that does not require the technical assumptions of signal detection theory. The results of this new analysis suggest that the detection criterion is never biased toward either response, even when the signal rate is low and the time on task is long. Two modifications of the signal detection theory framework are considered to account for this seemingly paradoxical result. The first assumes that the signal rate affects the relative sizes of the variances of the information distributions; the second assumes that the signal rate affects the logic of the operator's stopping rule. Actual or potential applications of this research include the improved training and performance assessment of operators in areas such as product quality control, air traffic control, and medical and clinical diagnosis. PMID- 9974233 TI - Evaluation of supermarket bagging using a wrist motion monitor. AB - The supermarket industry has one of the highest numbers of repeated trauma illnesses. Checkout departments have a rate of musculoskeletal injuries 2 to 3 times higher than that of other supermarket departments. The primary objective of this study was to quantify the wrist motions required to bag groceries using a wrist motion monitor. The wrist motions included deviations, velocities, and accelerations for flexion-extension, radial-ulnar, and pronation-supination directions. The independent variables were handle type and object location. Objects with finger-thumb couplings required more extreme pronations, greater wrist velocities for pronation-supination deviations, and greater wrist accelerations for pronation-supination deviations than did other objects. Objects with 10-cm hand couplings required more extreme flexion, larger ranges of movement for radial-ulnar deviations and pronation-supination deviations, and greater wrist velocities in the radial-ulnar and pronation-supination directions than did 5-cm objects. The right and front locations required more extreme deviations than did the left and back locations. Because finger-thumb and 10-cm hand couplings require larger wrist deviations and greater velocities, these objects may pose a greater risk of developing cumulative trauma disorders to the bagger. Potential applications of this research include engineering design of grocery packaging and supermarket bagging workstations. PMID- 9974234 TI - How automatic is manual gear shifting? AB - Manual gear shifting is often used as an example of an automated (vs. controlled) process in driving. The present study provided an empirical evaluation of this assumption by evaluating sign detection and recall performance of novice and experienced drivers driving manual shift and automatic transmission cars in a downtown area requiring frequent gear shifting. The results showed that manual gear shifting significantly impaired sign detection performance of novice drivers using manual gears compared with novice drivers using an automatic transmission, whereas no such differences existed between the two transmission types for experienced drivers. The results clearly demonstrate that manual gear shifting is a complex psychomotor skill that is not easily (or quickly) automated and that until it becomes automated, it is an attention-demanding task that may impair other monitoring aspects of driving performance. Actual or potential applications of this research include a reevaluation of the learning process in driving and the need for phased instruction in driving from automatic gears to manual gears. PMID- 9974369 TI - Low molecular weight heparin versus acenocoumarol in the secondary prophylaxis of deep vein thrombosis. AB - The aim of this study was to determine the efficacy and safety of subcutaneous weight-adjusted dose low molecular weight heparin (LMWH) compared with oral anticoagulant (OA) in the prevention of recurrent venous thromboembolism. In a prospective multicenter trial, 202 patients with symptomatic proximal deep vein thrombosis (DVT) were included. As soon as the diagnosis of DVT was confirmed by phlebography, 101 were randomly assigned to receive LMWH (nadroparin) for secondary prophylaxis and 101 to receive OA (acenocoumarol). Patients in both groups were initially treated with nadroparin in a dose of 85 anti-Xa IU/kg s.c. every 12 h. Secondary prophylaxis with either nadroparin, 85 anti-Xa IU/kg s. c. once daily, or acenocoumarol was continued for at least 3 months. Three patients in the LMWH group and 6 in the OA group were excluded from analysis for various reasons. During the one-year combined secondary prophylaxis and surveillance period, 7 of of the 98 evaluable patients (7.1%) in the LMWH group and 9 of the 95 evaluable patients (9.5%) in the OA group had a documented recurrence of venous thromboembolism (Fisher's exact test, p = 0.61). Of these, 2 patients who received LMWH and 7 patients on acenocoumarol had recurrences in the 3-month period of secondary prophylaxis. Four patients (4.1%) in the LMWH group developed bleeding complications during this study period, as compared with 7 (7.4%) in the OA group (Fisher's exact test, p = 0.37). There were two major bleedings, one in the LMWH group and one in the OA group. Eleven patients died, 5 (5.1%) in the LMWH group and 6 (6.3%) in the OA group. It is concluded that nadroparin in a dose of 85 anti-Xa IU/kg s.c. once daily provides an effective and safe alternative to oral anticoagulants in the secondary prophylaxis of DVT. PMID- 9974370 TI - Thrombomodulin: a new marker for placental abruption. AB - Thrombomodulin (TM), a marker of endothelial cell damage, has been localized to the placental syncytiotrophoblast. A prospective cohort study of twenty-five pregnant women who were admitted with a clinical diagnosis of placental abruption was undertaken. Abruption was confirmed after delivery in eight cases (Group 1). Group 2 consisted of seventeen patients with no clinical or pathologic evidence of placental abruption after delivery. TM was significantly elevated in Group 1 (71.59+/-5.35 vs. 48.29+/-3.53 ng/ml, p = 0.001). The sensitivity and specificity of TM > or =60 ng/ml as a marker for abruption was 87.5 and 76.5%, respectively. In comparison, the sensitivity of an abnormal coagulation profile, maternal Kleihauer-Betke and ultrasound in patients with abruption was 0, 16.7 and 28.6%, respectively. TM is a highly sensitive and specific marker for acute placental abruption. PMID- 9974371 TI - Immune tolerance therapy for haemophilia A patients with acquired factor VIII alloantibodies: comprehensive analysis of experience at a single institution. AB - Immune Tolerance Therapy for Haemophilia A Patients with Acquired Factor VIII Alloantibodies: Comprehensive Analysis of Experience at a Single Institution Eleven children with severe haemophilia A associated with the IVS 22 inversion and acquired high titre neutralising antibodies to factor VIII underwent immune tolerance induction. HLA class I and high resolution class II type is detailed for each patient. A three phase approach to immune tolerance induction was used. During phase 1, which lasted a median of six weeks, patients received factor VIII 100 IU/kg twice daily. Phase 2 comprised a factor VIII dose reduction to 100 IU/kg once daily, and continued for a median duration of 14 weeks. Subsequently 10 of the 11 patients satisfied the criteria of absent factor VIII neutralising activity by the Bethesda method, and a factor VIII elimination half life of greater than 5 h, allowing progression to phase 3, a further factor VIII dose reduction to 50 IU/kg three times weekly. A model for dose reduction as factor VIII tolerance evolves, based on pharmacokinetic analysis, is described. PMID- 9974372 TI - Inhibitors in German hemophilia A patients treated with a double virus inactivated factor VIII concentrate bind to the C2 domain of FVIII light chain. AB - To reduce the risk of transmission of hepatitis A virus, an Octapharma produced factor VIII (fVIII) concentrate treated with solvent detergent (FVIII-SD) was further pasteurized after purification. This product, Octavi SDPlus (FVIII-SDP), was marketed in Europe in 1993 to 1995. Inhibitors appeared from September to October, 1995, in 12 of 109 previously treated German hemophilia A patients. A study of similarly treated Belgian patients, who also developed inhibitors, had shown antibodies to the fVIII light chain (domains A3-C1-C2) only. In the present study, the epitope specificity of 8 German inhibitor plasmas was also found to be restricted to the light chain. In radioimmunoprecipitation assays to localize the light chain epitope(s), antibody binding to heavy chain (domains A1-A2-B) was 11 148 fold lower than to the C2 domain, and binding to recombinant A3-C1 was barely detectable. These results were supported by >95% neutralization of a high responder inhibitor titer by the C2 domain. PMID- 9974373 TI - TFPIbeta, a second product from the mouse tissue factor pathway inhibitor (TFPI) gene. AB - Tissue factor pathway inhibitor (TFPI) contains three Kunitz domains separated by two connecting regions. We have cloned another naturally occurring TFPI gene product from a mouse lung cDNA library which we have called TFPIbeta. TFPIbeta is derived from alternative splicing of the TFPI gene. Analysis of the cDNA shows that mouse TFPIbeta protein is identical to TFPI from the N'-terminus through the second connecting region. However, mouse TFPIbeta possesses neither a third Kunitz domain nor an Arg, Lys-rich C'-terminus but instead has a completely different C'-terminal (beta-domain) sequence which is not homologous to any known protein. Northern blot analyses show that the tissues for mouse TFPIbeta synthesis are heart and lung; in contrast, TFPI appears in Northern blots of heart and spleen. Both TFPIbeta and TFPI messages first appear in 7-day-old mouse embryos, but only the TFPI mRNA persists until 17 days. Purified recombinant TFPIbeta shows an apparent molecular weight of 38 kDa. Kinetic studies indicate that mouse TFPIbeta is a slow-binding enzyme inhibitor for human factor Xa. In addition, heparin does not enhance the inhibition of factor Xa by mouse TFPIbeta although it does accelerate factor Xa inhibition by TFPI. PMID- 9974375 TI - A new enzyme immunoassay for soluble fibrin in plasma, with a high discriminating power for thrombotic disorders. AB - Fibrin formation is a multistep process initiated by thrombin. At first thrombin converts fibrinogen to fibrin molecules which in vivo form soluble complexes with fibrinogen. Soluble fibrin is considered to be an early biochemical marker for intravascular fibrin formation and impending thrombotic events, such as deep venous thrombosis (DVT), pulmonary embolism (PE) and disseminated intravascular coagulopathy (DIC). A new enzyme immunoassay (EIA) was developed on the basis of a monoclonal antibody directed against a fibrin specific neo-epitope located on the gamma-chain of fibrinogen; gamma-(312-324). In addition, it was possible to prepare a lyophilized reference material of thrombin-generated soluble fibrin, that allowed for full antigen recovery after reconstitution with buffer. Assay conditions, e.g. solid phase-Ig concentration and buffer composition, sample and conjugate dilution, and incubation times were optimised. The present assay was found to be specific (no interference of homologous antigens) and reproducible (intra-assay CV 4-8%, interassay CV 4-9%), and therefore highly suited for measuring soluble fibrin levels in a plasma milieu. The median normal value for soluble fibrin was determined in plasma samples obtained from apparently healthy volunteers (n = 81) and found to be 0.040 microg/ml, with a range (10-90 percentiles) of 0.026-0.059 microg/ml. A retrospective study showed that soluble fibrin levels were highly significantly increased in patients with a confirmed diagnosis of DIC (median 1.042 microg FEU/ml, range 0.160-2.319 microg/ml, n = 21, P<0.0001 vs. normal). PE (median 0.527 microg FEU/ml, range 0.084-1.234 microg/ml, n = 29, P<0.0001 vs normal) and DVT (median 0.126 microg FEU/ml, range 0.059-0.878 microg/ml, n = 36, P<0.0001 vs. normal), as determined by the Mann Whitney U-Test. PMID- 9974374 TI - Performance of a new fibrin monomer assay to exclude deep vein thrombosis in symptomatic outpatients. AB - In this study we prospectively assessed the reliability of a new fibrin monomer assay in 106 outpatients with clinically suspected deep venous thrombosis of the lower limb. According to the results of the objective tests and using different cut-off points we calculated the sensitivity, specificity and negative predictive value of the fibrin monomer assay. The prevalence of deep vein thrombosis was 44.3% (31.1% proximal, 13.2% distal). Using a cut-off level of plasma fibrin monomer of 3.5 microg/ml, a sensitivity, specificity and negative predictive value of 100% (95% CI: 94-100%), 35.6% (95% CI: 23-48%) and 100% (95% CI: 86 100%), respectively, were obtained. The exclusion rate was 19.8% (95% CI: 12-27%) of all referred patients. These accuracy indices compared favourably with the respective results of a routine D-dimer ELISA used for comparison. CONCLUSION: This new fibrin monomer assay appears to be a reliable method for the exclusion of deep vein thrombosis in symptomatic outpatients. PMID- 9974376 TI - Local calibration of international normalised ratio improves between laboratory agreement: results from the UK National External Quality Assessment Scheme. UK NEQAS (Blood Coagulation) Steering Committee. AB - In the present study we have performed local calibration of International Normalised Ratio (INR) measurement systems in a large series of laboratories. We assigned INRs to five lyophilised plasma calibrants, one prepared from normal plasma and four using plasma from warfarinised patients, using different International Reference Preparations for Thromboplastin. These five calibrants, and two lyophilised test plasmas were analysed by 349 centres using 60 different thromboplastin instrument combinations. Plasma calibrants were assigned INRs using the WHO reference thromboplastin RBT-90 or the European reference thromboplastin CRM 149R. Each participating centre determined PTs of the calibrants with their local system. These PTs were then used to construct a local calibration graph relating PT to INR. The PTs of test plasmas were converted directly into INR using the local calibration model and into INR using the conventional method. The overall medians of conventionally derived INRs of two test plasmas analysed in 349 centres were 2.50 and 3.10, compared to 2.47 and 3.04 after local calibration where RBT-90 was employed to assign INRs to calibrants. Use of CRM 149R to assign INRs to calibrants led to a significant (p<0.0001) increase in INR to 2.7 and 3.36 respectively. When results were grouped according to the thromboplastin employed, agreement between results with different reagents was improved by local calibration. There was a significant reduction (p<0.01) in the spread of results in different centres as indicated by a reduction in coefficient of variation. PMID- 9974377 TI - Influence of three types of automated coagulometers on the international sensitivity index (ISI) of rabbit, human, and recombinant human tissue factor preparations--a multicenter study. AB - Five tissue factor reagents and three types of automated instruments for prothrombin time (PT) determination were studied in an international multicenter collaborative exercise. The purpose of this work was to determine the international sensitivity index (ISI) for each combination of reagent and instrument against the international reference preparation RBT/90. Each type of instrument was used by 3 or 4 centers to assess the interlaboratory variation of the ISI. The interlaboratory variation of the ISI for each combination of reagent and instrument ranged between 0.4% and 7.8% coefficient of variation. For three reagents, the mean ISI values for ACL (nephelometric) and STA (mechanical) were practically identical, but the mean ISI values for MLA (photo-optical) were at least 10% higher. For two other reagents prepared from rabbit tissue, the mean ISI values increased in the order ACL, STA, MLA. The widest range of mean ISI values was noted with one rabbit tissue factor reagent: 1.68 for ACL and 2.00 for MLA. Exclusion of patient specimens with INR <1.5 and INR >4.5 determined by the international reference preparation resulted in a slight decrease of the mean ISI. The interlaboratory variation of the International Normalized Ratio (INR) was assessed from the results obtained with common lyophilized and deep-frozen plasmas. The use of instrument-specific ISI values resulted in reduced interlaboratory variation of the INR. It is recommended that thromboplastin manufacturers provide instrument-specific ISI values. PMID- 9974378 TI - A longitudinal study of the relationships between haemostatic, lipid, and oestradiol changes during normal human pregnancy. AB - Increased activation of both blood coagulation and fibrinolysis occurs during normal pregnancy. The responsible mechanisms are unclear, but may include increases in both oestradiol and blood lipids. We, therefore, studied the associations between fasting serum oestradiol, plasma cholesterol and triglyceride, and Factor VII activity, PAI activity, t-PA antigen, fibrin D dimer, and vWF antigen in 10 women, each sampled on 6 occasions between 10 weeks and 35 weeks during normal pregnancy. Strong and similar individual correlations were observed between increases in FVII, PAI, t-PA and D-dimer (but not vWF) and increases in both oestradiol and triglyceride. Associations between increments in plasma cholesterol and haemostatic factors (except for FVII), were somewhat weaker. We, therefore, suggest that oestradiol-induced hypertriglyceridaemia may be a cause of elevations in plasma Factor VII activity, PAI and t-PA, and fibrin turnover (D-dimer) during normal pregnancy, but is poorly related to the increase in vWF antigen. PMID- 9974379 TI - Double fluorescent-amplification refractory mutation detection (dF-ARMS) of the factor V Leiden and prothrombin mutations. AB - Simultaneous fluorescent [F] detection of the factor V Leiden (G1691A) and the prothrombin 3'-untranslated region (G20210A) mutations were performed in a single tube polymerase chain reaction (PCR). Amplification refractory mutation detection system (ARMS) formed the basis of this assay design. Fluorescent-labelled primers incorporated into amplicons during the reaction facilitated detection directly by GeneScan analysis without further manipulation. To test the efficacy of this double [F]-ARMS (dF-ARMS) method, 48 patients with unexplained thrombotic tendencies were investigated for their factor V Leiden and prothrombin genotypes. These results corresponded exactly with data achieved using the more conventional methods of restriction fragment length polymorphism (RFLP)-PCR and direct DNA sequencing. Three out of the 48 patients in this group were found to be compound heterozygotes. PMID- 9974381 TI - Genesis and evolution of the 1997-98 El Nino AB - The 1997-98 El Nino was, by some measures, the strongest on record, with major climatic impacts felt around the world. A newly completed tropical Pacific atmosphere-ocean observing system documented this El Nino from its rapid onset to its sudden demise in greater detail than was ever before possible. The unprecedented measurements challenge existing theories about El Nino-related climate swings and suggest why climate forecast models underpredicted the strength of the El Nino before its onset. PMID- 9974380 TI - Efficient bypass of a thymine-thymine dimer by yeast DNA polymerase, Poleta. AB - The RAD30 gene of the yeast Saccharomyces cerevisiae is required for the error free postreplicational repair of DNA that has been damaged by ultraviolet irradiation. Here, RAD30 is shown to encode a DNA polymerase that can replicate efficiently past a thymine-thymine cis-syn cyclobutane dimer, a lesion that normally blocks DNA polymerases. When incubated in vitro with all four nucleotides, Rad30 incorporates two adenines opposite the thymine-thymine dimer. Rad30 is the seventh eukaryotic DNA polymerase to be described and hence is named DNA polymerase eta. PMID- 9974383 TI - Giant wormlike rubber micelles AB - A low molecular weight poly(ethyleneoxide)-poly(butadiene) (PEO-PB) diblock copolymer containing 50 weight percent PEO forms gigantic wormlike micelles at low concentrations (<5 percent by weight) in water. Subsequent generation of free radicals with a conventional water-based redox reaction leads to chemical cross linking of the PB cores without disruption of the cylindrical morphology, as evidenced by cryotransmission electron microscopy and small-angle neutron scattering experiments. These wormlike rubber micelles exhibit unusual viscoelastic properties in water. PMID- 9974382 TI - Mechanism of zeolite A nanocrystal growth from colloids at room temperature. AB - The formation and growth of crystal nuclei of zeolite A from clear solutions at room temperature were studied with low-dose, high-resolution transmission electron microscopy in field emission mode and with in situ dynamic light scattering. Single zeolite A crystals nucleated in amorphous gel particles of 40 to 80 nanometers within 3 days at room temperature. The resulting nanoscale single crystals (10 to 30 nanometers) were embedded in the amorphous gel particles. The gel particles were consumed during further crystal growth at room temperature, forming a colloidal suspension of zeolite A nanocrystals of 40 to 80 nanometers. On heating this suspension at 80 degrees C, solution-mediated transport resulted in additional substantial crystal growth. PMID- 9974385 TI - Dislocations faster than the speed of sound AB - It is thought that dislocations cannot surpass the sound barrier at the shear wave velocity because the energy spent in radiation has a singularity there. Atomistic simulations show that dislocations can move faster than the speed of sound if they are created as supersonic dislocations at a strong stress concentration and are subjected to high shear stresses. This behavior is important for the understanding of low-temperature deformation processes such as mechanical twinning and may be relevant for the dynamics of tectonic faults. The motion of the dislocations at a speed of 2 times the shear wave velocity can be understood from a linear elastic analysis, but many of the peculiarities of the supersonic dislocations are dominated by nonlinear effects that require a realistic atomistic description. PMID- 9974384 TI - Ordered mesoporous polymers of tunable pore size from colloidal silica templates. AB - Ordered mesoporous polymers have been prepared by replication of colloidal crystals made from silica spheres 35 nanometers in diameter. The pores in the colloidal crystals were filled with divinylbenzene (DVB), ethyleneglycol dimethacrylate (EDMA), or a mixture of the two. Polymerization and subsequent dissolution of the silica template leaves a polycrystalline network of interconnected pores. When mixtures of DVB and EDMA are used, the pore size of the polymer replicas can be varied continuously between 35 and 15 nanometers because the polymer shrinks when the silica template is removed. PMID- 9974386 TI - Chemical analysis of polar stratospheric cloud particles AB - A balloon-borne gondola carrying a particle analysis system, a backscatter sonde, and pressure and temperature sensors was launched from Kiruna, Sweden, on 25 January 1998. Measurements within polar stratospheric cloud layers inside the Arctic polar vortex show a close correlation between large backscatter ratios and enhanced particle-related water and nitric acid signals at low temperatures. Periodic structures in the data indicate the presence of lee waves. The H2O/HNO3 molar ratios are consistently found to be above 10 at atmospheric temperatures between 189 and 192 kelvin. Such high ratios indicate ternary solution particles of H2O, HNO3, and H2SO4 rather than the presence of solid hydrates. PMID- 9974387 TI - A 0.5-million-year record of millennial-scale climate variability in the north atlantic AB - Long, continuous, marine sediment records from the subpolar North Atlantic document the glacial modulation of regional climate instability throughout the past 0.5 million years. Whenever ice sheet size surpasses a critical threshold indicated by the benthic oxygen isotope (delta18O) value of 3.5 per mil during each of the past five glaciation cycles, indicators of iceberg discharge and sea surface temperature display dramatically larger amplitudes of millennial-scale variability than when ice sheets are small. Sea-surface temperature oscillations of 1 degrees to 2 degreesC increase in size to approximately 4 degrees to 6 degreesC, and catastrophic iceberg discharges begin alternating repeatedly with brief quiescent intervals. The glacial growth associated with this amplification threshold represents a relatively small departure from the modern ice sheet configuration and sea level. Instability characterizes nearly all observed climate states, with the exception of a limited range of baseline conditions that includes the current Holocene interglacial. PMID- 9974388 TI - A kuroko-type polymetallic sulfide deposit in a submarine silicic caldera AB - Manned submersible studies have delineated a large and actively growing Kuroko type volcanogenic massive sulfide deposit 400 kilometers south of Tokyo in Myojin Knoll submarine caldera. The sulfide body is located on the caldera floor at a depth of 1210 to 1360 meters, has an area of 400 by 400 by 30 meters, and is notably rich in gold and silver. The discovery of a large Kuroko-type polymetallic sulfide deposit in this arc-front caldera raises the possibility that the numerous unexplored submarine silicic calderas elsewhere might have similar deposits. PMID- 9974389 TI - A giant protease with potential to substitute for some functions of the proteasome. AB - An alanyl-alanyl-phenylalanyl-7-amino-4-methylcoumarin-hydrolyzing protease particle copurifying with 26S proteasomes was isolated and identified as tripeptidyl peptidase II (TPPII), a cytosolic subtilisin-like peptidase of unknown function. The particle is larger than the 26S proteasome and has a rod shaped, dynamic supramolecular structure. TPPII exhibits enhanced activity in proteasome inhibitor-adapted cells and degrades polypeptides by exo- as well as predominantly trypsin-like endoproteolytic cleavage. TPPII may thus participate in extralysosomal polypeptide degradation and may in part account for nonproteasomal epitope generation as postulated for certain major histocompatibility complex class I alleles. In addition, TPPII may be able to substitute for some metabolic functions of the proteasome. PMID- 9974390 TI - Role of NADH shuttle system in glucose-induced activation of mitochondrial metabolism and insulin secretion. AB - Glucose metabolism in glycolysis and in mitochondria is pivotal to glucose induced insulin secretion from pancreatic beta cells. One or more factors derived from glycolysis other than pyruvate appear to be required for the generation of mitochondrial signals that lead to insulin secretion. The electrons of the glycolysis-derived reduced form of nicotinamide adenine dinucleotide (NADH) are transferred to mitochondria through the NADH shuttle system. By abolishing the NADH shuttle function, glucose-induced increases in NADH autofluorescence, mitochondrial membrane potential, and adenosine triphosphate content were reduced and glucose-induced insulin secretion was abrogated. The NADH shuttle evidently couples glycolysis with activation of mitochondrial energy metabolism to trigger insulin secretion. PMID- 9974391 TI - Conserved structures of mediator and RNA polymerase II holoenzyme. AB - Single particles of the mediator of transcriptional regulation (Mediator) and of RNA polymerase II holoenzyme were revealed by electron microscopy and image processing. Mediator alone appeared compact, but at high pH or in the presence of RNA polymerase II it displayed an extended conformation. Holoenzyme contained Mediator in a fully extended state, partially enveloping the globular polymerase, with points of apparent contact in the vicinity of the polymerase carboxyl terminal domain and the DNA-binding channel. A similarity in appearance and conformational behavior of yeast and murine complexes indicates a conservation of Mediator structure among eukaryotes. PMID- 9974392 TI - Crystallographic evidence for preformed dimers of erythropoietin receptor before ligand activation. AB - Erythropoietin receptor (EPOR) is thought to be activated by ligand-induced homodimerization. However, structures of agonist and antagonist peptide complexes of EPOR, as well as an EPO-EPOR complex, have shown that the actual dimer configuration is critical for the biological response and signal efficiency. The crystal structure of the extracellular domain of EPOR in its unliganded form at 2.4 angstrom resolution has revealed a dimer in which the individual membrane spanning and intracellular domains would be too far apart to permit phosphorylation by JAK2. This unliganded EPOR dimer is formed from self association of the same key binding site residues that interact with EPO-mimetic peptide and EPO ligands. This model for a preformed dimer on the cell surface provides insights into the organization, activation, and plasticity of recognition of hematopoietic cell surface receptors. PMID- 9974393 TI - Erythropoietin receptor activation by a ligand-induced conformation change. AB - Erythropoietin and other cytokine receptors are thought to be activated through hormone-induced dimerization and autophosphorylation of JAK kinases associated with the receptor intracellular domains. An in vivo protein fragment complementation assay was used to obtain evidence for an alternative mechanism in which unliganded erythropoietin receptor dimers exist in a conformation that prevents activation of JAK2 but then undergo a ligand-induced conformation change that allows JAK2 to be activated. These results are consistent with crystallographic evidence of distinct dimeric configurations for unliganded and ligand-bound forms of the erythropoietin receptor. PMID- 9974394 TI - Hunting behavior of a marine mammal beneath the antarctic fast Ice AB - The hunting behavior of a marine mammal was studied beneath the Antarctic fast ice with an animal-borne video system and data recorder. Weddell seals stalked large Antarctic cod and the smaller subice fish Pagothenia borchgrevinki, often with the under-ice surface for backlighting, which implies that vision is important for hunting. They approached to within centimeters of cod without startling the fish. Seals flushed P. borchgrevinki by blowing air into subice crevices or pursued them into the platelet ice. These observations highlight the broad range of insights that are possible with simultaneous recordings of video, audio, three-dimensional dive paths, and locomotor effort. PMID- 9974395 TI - A copper cofactor for the ethylene receptor ETR1 from Arabidopsis. AB - The ETR1 receptor from Arabidopsis binds the gaseous hormone ethylene. A copper ion associated with the ethylene-binding domain is required for high-affinity ethylene-binding activity. A missense mutation in the domain that renders the plant insensitive to ethylene eliminates both ethylene binding and the interaction of copper with the receptor. A sequence from the genome of the cyanobacterium Synechocystis sp. strain 6803 that shows homology to the ethylene binding domain of ETR1 encodes a functional ethylene-binding protein. On the basis of sequence conservation between the Arabidopsis and the cyanobacterial ethylene-binding domains and on in vitro mutagenesis of ETR1, a structural model for this copper-based ethylene sensor domain is presented. PMID- 9974396 TI - A molecular phylogeny of reptiles. AB - The classical phylogeny of living reptiles pairs crocodilians with birds, tuataras with squamates, and places turtles at the base of the tree. New evidence from two nuclear genes, and analyses of mitochondrial DNA and 22 additional nuclear genes, join crocodilians with turtles and place squamates at the base of the tree. Morphological and paleontological evidence for this molecular phylogeny is unclear. Molecular time estimates support a Triassic origin for the major groups of living reptiles. PMID- 9974397 TI - Systematic review on the risk and benefit of different cholesterol-lowering interventions. AB - Meta-analyses have investigated the efficacy of cholesterol-lowering interventions in relation to the underlying risk of coronary heart disease and the extent and duration of cholesterol reduction. We systematically reviewed the efficacy of antilipidemic interventions on major mortality outcomes in relation to drug classes. We searched MEDLINE and EMBASE from 1966 through October 1996 for randomized, controlled trials of any cholesterol-lowering interventions reporting mortality data. We included 59 trials involving 85 431 participants in the intervention and 87 729 participants in the control groups. We pooled these trials into 7 pharmacological categories of cholesterol-lowering interventions: statins (13 trials), fibrates (12 trials), resins (8 trials), hormones (8 trials), niacin acid (2 trials), n-3 fatty acids (3 trials), and dietary interventions (16 trials). Of the cholesterol-lowering interventions, only statins showed a large and statistically significant reduction in mortality from coronary heart disease (risk ratio, 0.66; 95% confidence interval [CI], 0.54 to 0. 79) and from all causes (risk ratio, 0.75; 95% CI, 0.65 to 0.86). For both all cause and cardiovascular mortality, the difference between statins and the combined estimate of the other classes of agents was unlikely to be due to chance (P<0.02 for both comparisons). Meta-regression analysis demonstrated that variability in results across trials could be largely explained on the basis of differences in the magnitude of cholesterol reduction. Statins have the largest effect on the reduction of cardiovascular and all-cause mortality, and this result recommends their use in preference to other antilipidemic agents. The greater effect of statins is likely due to the larger reduction in cholesterol. PMID- 9974398 TI - Vascular gene transfer : from bench to bedside. PMID- 9974399 TI - Genetic analysis of the thermolabile variant of 5, 10-methylenetetrahydrofolate reductase as a risk factor for ischemic stroke. AB - Mild hyperhomocysteinemia is a risk factor for atherosclerotic vascular disease. Homozygosity for the C677T mutation in the gene for 5,10 methylenetetrahydrofolate reductase (MTHFR) is frequently associated with hyperhomocysteinemia, particularly in individuals with low levels of serum folate, and has been directly associated with cardiovascular disease in certain populations. The purpose of this study was to establish whether the C677T mutation, which causes thermolabile MTHFR, is a risk factor for ischemic stroke in the Irish population. The homozygous C677T genotype has previously been associated with coronary heart disease in Ireland. We collected blood from 174 individuals (minimum age 60 years) who had suffered an ischemic stroke that was confirmed by computed tomography brain scan. Control subjects (n=183) aged >/=60 years, who had never suffered a stroke or transient ischemic attack, were recruited from hospitals and active retirement groups in the same geographical area. MTHFR genotypes were determined and other known risk factors for stroke were documented. In the control group, the frequency of subjects with the homozygous C677T genotype was 10.4%. In patients who had suffered ischemic stroke, the frequency was 15.5%. This difference was not statistically significant. The odds ratio of stroke for C677T homozygotes, with other genotypes as a reference group, was 1.59, 95% CI=0.85, 2.97. The data indicate that the homozygous C677T MTHFR genotype is at most a moderate risk factor for ischemic stroke. PMID- 9974400 TI - Expression of markers of platelet activation and the interpatient variation in response to abciximab. AB - Our study concerns the biological effects of abciximab (c7E3 Fab, ReoPro), a powerful new antiplatelet drug that blocks glycoprotein (GP) IIb-IIIa complexes. Samples were examined from 6 patients with coronary artery disease who received a bolus of abciximab followed by a 10- microg/min infusion for at least 18 hours before percutaneous transluminal coronary angioplasty. Inhibition of ADP-induced PA was maximal for 4 patients but partial (79% and 53%) for 2 others during the infusion. Flow cytometry performed with monoclonal antibodies (PAC-1, AP-6, and F26) specific for the "activated" GP IIb-IIIa complex revealed large decreases in the expression of activation markers on platelets during therapy, but these decreases were less marked when inhibition of ADP-induced PA was incomplete. Residual aggregation was seen for all patients during the infusion when TRAP 14 mer peptide or thrombin was the stimulus. Unblocked GP IIb-IIIa complexes were detected on thrombin-stimulated platelets from the patients by immunoelectron microscopy performed using the monoclonal antibody AP-2. Unblocked GP IIb-IIIa complexes were also detected by flow cytometry when platelets preincubated for 1 hour in vitro with abciximab under saturating conditions were (1) incubated with TRAP 14-mer or (2) permeabilized with Triton X-100. In confirming interpatient variation in the platelet response to a standard dose of abciximab, our results also show that an uninhibited internal pool of GP IIb-IIIa complexes may mediate a residual response to strong agonists. PMID- 9974401 TI - Oleic acid inhibits endothelial activation : A direct vascular antiatherogenic mechanism of a nutritional component in the mediterranean diet. AB - Because oleic acid is implicated in the antiatherogenic effects attributed to the Mediterranean diet, we investigated whether this fatty acid can modulate endothelial activation, ie, the concerted expression of gene products involved in leukocyte recruitment and early atherogenesis. We incubated sodium oleate with human umbilical vein endothelial cells for 0 to 72 hours, followed by coincubation of oleate with human recombinant tumor necrosis factor, interleukin (IL)-1alpha, IL-1beta, IL-4, Escherichia coli lipopolysaccharide (LPS), or phorbol 12-myristate 13-acetate for a further 6 to 24 hours. The endothelial expression of vascular cell adhesion molecule-1 (VCAM-1), E-selectin, and intercellular adhesion molecule-1 was monitored by cell surface enzyme immunoassays or flow cytometry, and steady-state levels of VCAM-1 mRNA were assessed by Northern blot analysis. At 10 to 100 micromol/L for >24 hours, oleate inhibited the expression of all adhesion molecules tested. After a 72-hour incubation with oleate and a further 16-hour incubation with oleate plus 1 microg/mL LPS, VCAM-1 expression was reduced by >40% compared with control. Adhesion of monocytoid U937 cells to LPS-treated endothelial cells was reduced concomitantly. Oleate also produced a quantitatively similar reduction of VCAM-1 mRNA levels on Northern blot analysis and inhibited nuclear factor-kappaB activation on electrophoretic mobility shift assays. Incubation of endothelial cells with oleate for 72 hours decreased the relative proportions of saturated (palmitic and stearic) acids in total cell lipids and increased the proportions of oleate in total cell lipids without significantly changing the relative proportions of polyunsaturated fatty acids. Although less potent than polyunsaturated fatty acids in inhibiting endothelial activation, oleic acid may contribute to the prevention of atherogenesis through selective displacement of saturated fatty acids in cell membrane phospholipids and a consequent modulation of gene expression for molecules involved in monocyte recruitment. PMID- 9974402 TI - Adventitial angiogenesis early after coronary angioplasty : correlation with arterial remodeling. AB - The spatial correlation between arterial wall microvessels and the accumulation of atherosclerotic plaque is well documented. The role of these microvessels in the development of primary and restenotic lesions is not known. To investigate the effect of interventional procedures on arterial wall microvessels, we studied the adventitial microvascularity of porcine coronary arteries subjected to angioplasty. Twenty-two juvenile domestic swine were subjected to single or repeated (double) balloon angioplasty of the coronary arteries, with the interval between the first and second injury being 14 days. The number, density, and size of adventitial microvessels were measured 1 hour as well as 3, 7, 14, and 28 days after injury. One hour after single balloon injury, there were very few intact adventitial microvessels. Adventitial microvessel number, microvessel area density, and microvessel size were maximal 3 days after single (SI) and double (DI) injury but subsequently underwent progressive regression. Adventitial endothelial cell replication, as assessed by the incorporation of bromodeoxyuridine, was very low for the majority of arteries. Maximal endothelial cell replication indices were observed 3 days after SI and DI (eg, 12.0+/-3.3%). Early after SI the central arterial lumen area transiently increased, then renarrowed. The lumen area did not change after DI. Arterial remodeling occurred, as the accumulation of intimal and medial mass was correlated with expansion of the external elastic lamina. Adventitial microvessel area density was correlated with central arterial luminal area (R=0.34, P=0.04). The adventitial microvessel area density and the microvessel size index were greater late after DI compared with SI. These data indicate that adventitial angiogenesis occurs within 3 days after balloon injury and that regression of adventitial microvessels after SI corresponds with arterial narrowing. Changes in the adventitial microvasculature may be a component of arterial remodeling after balloon angioplasty. PMID- 9974403 TI - Low-density lipoprotein enhances platelet secretion via integrin-alphaIIbbeta3 mediated signaling. AB - LDL is known to increase the sensitivity of human platelets for agonists and to induce aggregation and secretion independently at high concentrations, but its mechanism of action is largely obscure. To clarify how LDL increases platelet sensitivity, cells were incubated in lipoprotein-poor plasma and treated with collagen at a concentration that induced approximately 20% secretion of 14C serotonin. Preincubation with LDL (30 minutes at 37 degreesC) enhanced secretion in a dose-dependent manner to 60+/-14% at a concentration of 2 g LDL protein/L. Similar stimulation by LDL was seen when secretion was induced by the thrombin receptor-activating peptide. This enhancement was strongly reduced (1) in the presence of monoclonal antibody PAC1 against activated alphaIIbbeta3, a polyclonal antibody against alphaIIb, and in the presence of the fibrinogen peptides GRGDS and HHLGGAKQAGDV; (2) in alphaIIbbeta3-deficient platelets; and (3) after dissociation of alphaIIbbeta3. In contrast, binding of 125I-LDL to normal platelets in the presence of PAC1, anti-alphaIIb, GRGDS, and HHLGGAKQAGDV, and to alphaIIbbeta3-deficient platelets was normal. LDL increased the surface expression of fibrinogen in lipoprotein-poor plasma and fibrinogen-free medium, suggesting that extracellular and granular fibrinogen bind to alphaIIbbeta3 after platelet-LDL interaction. Platelets deficient in fibrinogen (<0.5% of normal) or von Willebrand Factor (<1% of normal) but containing normal amounts of other ligands for alphaIIbbeta3 preserved responsiveness to LDL, indicating that occupancy of alphaIIbbeta3 was not restricted to fibrinogen. Inhibition of protein kinase C (bisindolylmaleimide) diminished fibrinogen binding and sensitization by LDL; inhibition of tyrosine kinases (herbimycin A) left fibrinogen binding unchanged but diminished sensitization by LDL. We conclude that an increased concentration of LDL, such as observed in homozygous familial hypercholesterolemia, sensitizes platelets to stimulation by collagen and thrombin receptor-activating peptide via ligand-induced outside-in signaling through integrin-alphaIIbbeta3. PMID- 9974404 TI - Two-chain factor VIIa generated in the pericardium during surgery with cardiopulmonary bypass : relationship to increased thrombin generation and heparin concentration. AB - Several recent studies have proposed that coagulation is triggered during cardiopulmonary bypass surgery by extrinsic pathway activation involving factor VIIa generation, but the methodology was indirect. Therefore, 12 patients were studied during routine cardiac and cardiopulmonary bypass surgery. Samples were taken before, during, and after bypass from the perfusate, from the aorta (retrograde cardiac drainage), pericardium, and collected suction fluid originating from the whole operative field. These samples were analyzed by enzyme linked immunosorbent assay for 2-chain factor VIIa, by prothrombin F1+2 assay, by thrombin-antithrombin (TAT) assay, and for heparin concentration. Factor VIIa, F1+2, and TAT levels in samples from the pericardium were greatly elevated (mean, 0.92 to 1.01, 227 to 334, and 399 to 526 microg/L, respectively; preoperative mean, 0.33, 32.3, and 1.90 microg/L, respectively; P<0. 05 for all), whereas levels in suction fluid were less consistently high. Factor VIIa and both F1+2 and thrombin-antithrombin levels in samples from the aorta, pericardium, and suction fluid were significantly correlated (r=0.57, P<0.001, n=111; and r=0.51, P<0. 001, n=105, respectively), and all were inversely correlated with heparin levels (r>-0.35, P<0.001, n>92). There was no evidence of factor VIIa generation in the circuit during bypass surgery, and both F1+2 and thrombin-antithrombin levels rose only approximately 2-fold, probably because heparin levels were higher than they were in the pericardium (P<0.05). We concluded that appreciable activation of factor VII occurs on the pericardium and that this is associated with increased thrombin generation. Ineffective local heparinization may be partly responsible. These results suggest that pericardium-induced activation of factor VII should be the target of anticoagulant strategies during cardiopulmonary bypass surgery. PMID- 9974405 TI - Expression of tissue inhibitor of metalloproteinase-1, -2, and -3 during neointima formation in organ cultures of human saphenous vein. AB - Degradation of the extracellular basement membrane is implicated in atherosclerosis, restenosis after angioplasty, and intimal thickening of vein grafts. Upregulation of metalloproteinase (MMP)-2 and MMP-9 accompanies neointima formation in cholesterol-fed rabbits, in rat and pig models of angioplasty, and in organ cultures of human saphenous veins. MMPs are inhibited by binding to tissue inhibitors of MMPs (TIMPs). Relatively little is known about their regulation in relationship to neointima formation; thus, we investigated TIMP expression in the organ culture model. Qualitative reverse transcriptase polymerase chain reaction of mRNA extracted from veins showed that TIMP-1, TIMP 2, and TIMP-3 are each expressed before and after culture. Zymography revealed that TIMP-1 was the most abundant TIMP secreted and that its secretion increased dramatically between 0 to 2 and 12 to 14 days of culture. An enzyme-linked immunosorbent assay showed that TIMP-1 secretion increased from 3.2+/-1.5 (mean+/ SE) to 32+/-6 ng/mg wet weight per day (n=5, P<0.01). Immunocytochemical testing localized the increased expression of TIMP-1 to neointimal smooth muscle cells. Although less abundant, TIMP-2 secretion also increased from 0.8+/-0. 3 to 4.7+/ 0.2 ng/mg wet weight per day (n=5, P<0.001), and tissue levels increased from 33+/-7 to 150+/-70 ng/mg wet weight (P<0.05). TIMP-2 was also immunolocalized to neointimal smooth muscle cells and their surrounding matrix. TIMP-3 was not secreted but was detected variably and constitutively in tissue extracts (160+/ 120 and 170+/-100 ng/mg wet weight [n=9] on days 2 and 14, respectively). TIMP-3 was found in the cells and extracellular matrix of the media and adventitia before culture and to a lesser extent in the neointima after 14 days of culture. Rates of total TIMP secretion on day 14 exceeded those of MMP-2 and MMP-9 (10.6+/ 1.9 and 15.6+/-2.3 ng/mg wet weight per day, respectively). Consistent with this, in situ zymography showed that MMP gelatinase activity was highly localized to cell bodies in the media and neointima. Secretion of TIMP-1 and TIMP-2 is greatly increased during neointima formation in human saphenous veins. TIMP-1 is readily released, whereas TIMP-2 remains partially attached and TIMP-3 exclusively attached to the extracellular matrix. Regulation of TIMP expression is therefore an important determinant of net MMP activity during neointima formation, restricting it to the pericellular environment. PMID- 9974406 TI - Mass concentration of plasma phospholipid transfer protein in normolipidemic, type IIa hyperlipidemic, type IIb hyperlipidemic, and non-insulin-dependent diabetic subjects as measured by a specific ELISA. AB - Mean plasma phospholipid transfer protein (PLTP) concentrations were measured for the first time by using a competitive enzyme-linked immunosorbent assay. PLTP mass levels and phospholipid transfer activity values, which were significantly correlated among normolipidemic plasma samples (r=0.787, P<0.0001), did not differ between normolipidemic subjects (3.95+/-1.04 mg/L and 575+/-81 nmol. mL-1. h-1, respectively; n=30), type IIa hyperlipidemic patients (4. 06+/-0.84 mg/L and 571+/-43 nmol. mL-1. h-1, respectively; n=36), and type IIb hyperlipidemic patients (3.90+/-0.79 mg/L and 575+/-48 nmol. mL-1. h-1, respectively; n=33). No significant correlations with plasma lipid parameters were observed among the various study groups. In contrast, plasma concentrations of the related cholesteryl ester transfer protein (CETP) were higher in type IIa and type IIb patients than in normolipidemic controls, and significant, positive correlations with total and low density lipoprotein cholesterol levels were noted. Interestingly, plasma PLTP mass concentration and plasma phospholipid transfer activity were significantly higher in patients with non-insulin-dependent diabetes mellitus (n=50) than in normolipidemic controls (6.76+/-1. 93 versus 3.95+/-1.04 mg/L, P<0.0001; and 685+/-75 versus 575+/-81 nmol. mL-1. h-1, P<0.0001, respectively). In contrast, CETP levels did not differ significantly between the 2 groups. Among non-insulin-dependent diabetes mellitus patients, PLTP levels were positively correlated with fasting glycemia and glycohemoglobin levels (r=0.341, P=0.0220; and r=0.382, P=0.0097, respectively) but not with plasma lipid parameters. It is proposed that plasma PLTP mass levels are related to glucose metabolism rather than to lipid metabolism. PMID- 9974407 TI - Study of the prothrombin gene 20201 GA variant in FV:Q506 carriers in relationship to the presence or absence of juvenile venous thromboembolism. AB - The G20210A transition of the prothrombin gene has been identified as a common but probably mild hereditary risk factor for venous thromboembolism (VTE). However, the prothrombin gene variant might contribute to the penetrance of thromboembolic disease in many patients with other prothrombotic defects, such as the FV:R506Q mutation. In this investigation, the A20210 allele was found in 9 of 450 healthy controls (2%). Among 89 asymptomatic FV:Q506 carriers, 3 subjects were doubly affected (3.4%). In contrast, of 263 unrelated carriers of the FV:Q506 mutant with a history of juvenile VTE, 30 also had the prothrombin gene G20210A variant (11.4%), including 25 of 220 patients who were heterozygous (11.4%) and 5 of 43 homozygous (11.6%) for FV:Q506. Thus, the A20210 allele of the prothrombin gene is significantly overrepresented in symptomatic FV:Q506 carriers compared with healthy controls (P<0.0001) and asymptomatic relatives carrying the FV mutant (P=0.02). Persons homozygous for the 20210A allele were not found. A statistically significant increase in the prevalence of more unusual sites of venous thrombosis at clinical onset was found in doubly affected patients (9 of 30; 30%) compared with patients without the prothrombin gene variant (26 of 233; 11. 1%) (P=0.004). First VTE occurred spontaneously in 53.3% of all doubly affected patients (16 of 30) and in 28.3% of all simply affected patients (66 of 233) (P=0.005). Among patients with VTE preceded by circumstantial risk factors, the A20210 allele was found in 7.7% (14 of 181). We conclude that the A20210 allele of the prothrombin gene is frequently coinherited in symptomatic FV:Q506 carriers and possibly influences age, site, and type of thrombotic onset manifestation in these patients. PMID- 9974408 TI - Fluid shear stress induction of the tissue factor promoter in vitro and in vivo is mediated by Egr-1. AB - Hemodynamic forces such as fluid shear stress have been shown to modulate the activity of an expanding family of genes involved in vessel wall homeostasis and the pathogenesis of vascular disease. We have investigated the effect of shear stress on tissue factor (TF) gene expression in human endothelial cells (ECs) and in a rat arterial model of occlusion. As measured by reverse transcriptase polymerase chain reaction, exposure of ECs to 1.5 N/m2 shear stress resulted in a time-dependent induction of endogenous TF transcripts of over 5-fold. Transient transfection of TF promoter mutants into cultured ECs suggests the involvement of the transcription factor Egr-1 in mediating the response of the TF promoter to shear stress. To address the importance of flow induction of Egr-1 in vivo, we have established a flow-restricted rat arterial model and determined the level of expressed Egr-1 and TF at the site of restricted flow using immunohistochemistry. We report an increase in the level of Egr-1 and TF protein in ECs expressed at the site of restricted flow. Elevated expression of Egr-1 and TF is restricted to a highly localized area, as evidenced by the fact that no significant increase in level can be detected at arterial sites distal to the site of occlusion. These findings suggest a direct role for Egr-1 in flow-mediated induction of TF and further substantiate the importance of shear stress as a modulator of vascular endothelial gene function in vivo. PMID- 9974409 TI - Urokinase activates the Jak/Stat signal transduction pathway in human vascular endothelial cells. AB - Endothelial cells demonstrate high urokinase expression and upregulation of urokinase receptors in response to vascular injury. Urokinase receptor binding facilitates endothelial cell migration into an arterial wound; however, the signaling cascade induced by the urokinase receptor in this cell type is incompletely understood. Because the Janus kinase (Jak)/signal transducer and activator of transcription (Stat) pathway seems to be important for vessel function, we investigated the hypothesis that urokinase receptor binding activates Jak/Stat signaling in human vascular endothelial cells. Incubation of endothelial cells with urokinase-type plasminogen activator (uPA,1 nmol/L) induced a rapid and pronounced increase in tyrosine phosphorylation of several proteins with a molecular weight between 80 to 90 and 130 to 140 kDa. The same pattern of tyrosine phosphorylation was found after treatment with 1 nmol/L ATF, the urokinase amino-terminal fragment, which is devoid of proteolytic activity but still binds to the urokinase receptor. Using coimmunoprecipitation techniques, we demonstrated that the activated urokinase receptor is associated with 2 cytoplasmic tyrosine kinases of the Jak family, viz, Jak1 and Tyk2. uPA and ATF induced a time-dependent activation of both kinases, as shown by immunoprecipitation and Western blot analysis. Using electrophoretic mobility shift and supershift assays, we then demonstrated that Stat1 is rapidly activated in endothelial cells in response to uPA and ATF. Furthermore, Stat1 specifically binds to the regulatory elements interferon-gamma activation site/interferon stimulated response element. The uPA-induced, time-dependent translocation of Stat1 to cell nuclei was confirmed by confocal microscopy study and immunoblotting of nuclear extracts with an anti-Stat1 antibody. This study provides evidence for a novel signaling pathway for uPA in human vascular endothelial cells. Direct activation of the Jak/Stat system via the uPA-receptor complex may be an important mechanism for endothelial cell migration and/or proliferation during angiogenesis and after vascular injury. PMID- 9974410 TI - Polymorphism of the methionine synthase gene : association with homocysteine metabolism and late-onset vascular diseases in the Japanese population. AB - Methionine synthase and 5,10-methylenetetrahydrofolate reductase (MTHFR) sequentially catalyze the remethylation of homocysteine to methionine. A point mutation in the encoding region of the methionine synthase gene, which results in substitution of an aspartic acid for a glycine residue (D919G), has been identified in patients of the cblG genetic complementation group; these patients exhibit significantly decreased methionine synthase activity. Nevertheless, the D919G mutation has also been reported to be common in the general population. In this study, we analyzed the distribution of methionine synthase D/G polymorphism in the Japanese population and examined the extent to which it is associated with altered homocysteine metabolism and late-onset vascular diseases. We studied 215 patients with coronary artery disease, 251 patients with histories of ischemic stroke, and 257 control subjects. The methionine synthase genotype was analyzed by polymerase chain reaction followed by HaeIII digestion; allele frequencies for the D919G variant of the enzyme proved to be similar in all 3 subject groups (control subjects, 0.17; coronary artery disease patients, 0. 17; and ischemic stroke patients, 0.19). Furthermore, in patients with ischemic stroke, plasma levels of homocyst(e)ine and folate were similar, irrespective of methionine synthase genotype. Thus, the methionine synthase D919G mutation was found to be common in the Japanese general population, and it appears unlikely that this polymorphism has a major effect on homocysteine metabolism and/or the onset of vascular diseases. PMID- 9974411 TI - The T allele of the hepatic lipase promoter variant C-480T is associated with increased fasting lipids and HDL and increased preprandial and postprandial LpCIII:B : European Atherosclerosis Research Study (EARS) II. AB - The common C-480T transition in the hepatic lipase (HL) promoter has been shown to be associated with lower HL activity and increased high density lipoprotein (HDL) cholesterol. We examined the frequency and lipid associations of this HL polymorphism in 385 healthy, young (18- to 28-year-old) men whose fathers had had a premature myocardial infarction (designated cases) and 405 age-matched controls. These individuals were participants in the European Atherosclerosis Research Study II postprandial trial, who had been recruited from 11 European countries in 4 regions (the Baltic; United Kingdom; and central and southern Europe). Overall, the frequency of the T allele was 0.207 in controls and 0.244 in cases (P=0.08). The T allele was associated with higher fasting plasma total cholesterol (P<0.01), triglycerides (P<0.01), and HDL cholesterol (P<0.01). The strongest association was found with apolipoprotein (apo) A-I concentration, which was 10% higher in individuals homozygous for the T allele compared with those homozygous for the C allele (P<0.001). This polymorphism had no effect on the rise in plasma triglyceride levels after a fatty meal. However, before and after the fat load was ingested, levels of particles containing both apoC-III and apoB (LpC-III:B) were higher in carriers of the T allele, with homozygotes having 23% and 27% higher levels preprandially and postprandially, respectively, than those homozygous for the C allele (P<0.05). Thus, our results demonstrate that the C-480T polymorphism in the HL promoter is associated with alterations in plasma lipids and lipoproteins and the accumulation of atherogenic LpC-III:B particles. PMID- 9974412 TI - Tissue factor pathway inhibitor is expressed by human monocyte-derived macrophages : relationship to tissue factor induction by cholesterol and oxidized LDL. AB - Lipid-laden macrophages express tissue factor (TF), which may activate the extrinsic coagulation pathway on rupture of the atherosclerotic plaque. Tissue factor pathway inhibitor (TFPI) is a major regulator of TF-induced coagulation. We evaluated the possibility that monocyte-derived macrophages express this protein, thereby contributing to regulation of TF activity (TFact). Equally, we investigated the effect of cholesterol and of oxidized LDL (Ox-LDL) on the expression of TFPI and TF by human monocyte-derived macrophages (HMDMs). Northern blot analysis of TFPI mRNA from cultured HMDMs revealed a single band at 4.2 kb with weak intensity; this finding was confirmed by reverse transcription polymerase chain reaction. Gel filtration of HMDM supernatants showed the presence of an active 100-kDa form of TFPI, which was confirmed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis under nonreducing conditions; under reducing conditions, however, the immunoblot revealed a 40-kDa form of TFPI. The TFPI in HMDM supernatants possessed heparin-binding affinity, suggesting potential interaction of TFPI with heparan sulfate proteoglycans. Stimulation of foam cell formation by incubation of macrophages for 48 hours with exogenous free cholesterol indicated that neither the biological activity nor the de novo synthesis of TFPI protein was affected. In contrast, cholesterol loading with exogenous free cholesterol induced significant upregulation of total TFact (2.6 fold: 25.0 versus 9.4 mU/mg cell protein, cholesterol-treated versus control cells; P<0. 05); such induction was not correlated with an elevation in TF antigen (8.5 versus 7.8 ng/mg cell protein, cholesterol-treated versus control cells). Similarly, cholesterol-rich Ox-LDL induced an increase in TFact (1.9 fold: 18.9 versus 10.0 mU/mg cell protein, Ox-LDL-treated versus control cells; P<0.05); by contrast, the amount of TF antigen remained unchanged (7.1 versus 7.9 ng/mg cell protein, Ox-LDL-treated versus control cells). Our data indicate that enhancement of the procoagulant activity of TF in macrophage-derived foam cells is not counterbalanced by upregulation of TFPI activity, suggesting that lesion foam cells are in a procoagulant state; they may therefore contribute to thrombus generation on plaque rupture. PMID- 9974413 TI - Determinants of plasma levels of plasminogen activator inhibitor-1 : A study of normotensive twins. AB - We investigated whether plasma levels of the plasminogen activator inhibitor type 1 antigen (PAI-1:Ag) are genetically determined in monozygotic (MZ) and dizygotic (DZ) twins. Twenty-five pairs of healthy twins underwent measurements of PAI-1:Ag and other variables, including body mass index, mean blood pressure, plasma renin activity, insulin, and glucose. To ascertain the zygosity of twins, highly discriminating micro- and minisatellite systems with variable numbers of tandem repeats were analyzed by PCR amplification followed by polyacrylamide gel electrophoresis. Subjects were also genotyped for the 4G/5G polymorphism by PCR. Estimates of genetic variance and heritability were obtained for PAI-1:Ag, and for body mass index, mean blood pressure, plasma renin activity, glucose, and insulin by jointly examining data in a path analysis with TWINAN90. Results showed that 12 pairs of twins were MZ and 13 were DZ. All tests of genetic variance [within pair (WP): F=6.24, P=0.002; among component (AC): F=2.62, P=0.04; average absolute difference t test=3. 00, P=0.004] showed significant genetic variance of PAI-1:Ag, but not of the other variables. Three tests of heritability (WP=0.837, P=0.002; AC=1.791, P<0.05; intraclass correlation: 1.180, P=0.001) consistently showed significant PAI-1:Ag heritability. Additive genetic influences (A), dominance genetic effect (D), and random environmental influences (E) accounted for 0.714, 0.154, and 0.132 of PAI-1:Ag variance, respectively. No effect of different 4G/5G genotypes was found. Thus, these results show significant genetic variance and heritability of PAI-1:Ag and suggest that A is more important than both D and E in determining PAI-1:Ag variance. PMID- 9974414 TI - Glucose phosphorylation is essential for the turnover of neutral lipid and the second stage assembly of triacylglycerol-rich ApoB-containing lipoproteins in primary hepatocyte cultures. AB - Primary hepatocytes cultured in a medium supplemented with amino acids and lipogenic substrates responded to increased extracellular glucose by increasing the secretion of VLDL apoB. This effect was accompanied by an increased secretion of VLDL triacylglycerol (TAG) derived from endogenous stores. Glucose also stimulated intracellular TAG mobilization via the TAG lipolysis/esterification cycle. All these effects were abolished in the presence of mannoheptulose (MH), an inhibitor of glucose phosphorylation. Glucose also gave rise to a modest (50% to 60%) increase in the incorporation of 35S methionine into newly synthesized apoB (P<0.05) and to a doubling of newly-synthesized apoB secretion as VLDL (P<0. 05). The magnitude of these effects was similar for apoB-48 and for apoB-100. MH inhibited apoB-48 and apoB-100 synthesis and VLDL secretion at all glucose concentrations. The effects of glucose and MH on the secretion of newly synthesized apoB-48 or apoB-100 as small dense particles were less pronounced. Glucose had no effects on the posttranslational degradation of newly-synthesized apoB-100 or apoB-48. However, this process was significantly enhanced by MH. The results suggest that glucose stimulates TAG synthesis, turnover, and output as VLDL. These effects are associated with an increased VLDL output of apoB mediated mainly by an increase in the net synthesis of both apoB-48 and apoB-100. All these changes are prevented by interference with glucose phosphorylation. Output of small, dense, apoB-containing particles is relatively unaffected by the glucose and MH-induced changes in TAG synthesis and lipolysis, an observation which suggests that only the bulk lipid addition step of VLDL assembly is affected by changes in glucose metabolism. PMID- 9974415 TI - Serum paraoxonase after myocardial infarction. AB - HDL has been shown to prevent the oxidative modification of LDL. The antioxidant activity of HDL is believed to reside in its enzymes, particularly paraoxonase. Human serum paraoxonase (PON1) is closely associated with a specific HDL subfraction also containing apoA1 and clusterin. Recently PON1 has been implicated in the pathogenesis of atherosclerosis. We have examined the activity, concentration, and specific activity of PON1 in 50 patients on admission to hospital immediately after acute myocardial infarction (MI) and in 48 age- and gender-matched controls. Serum PON1 activity and concentration were significantly lower in patients with MI than in controls (activity, 221.5 [99.3 to 303.2] nmol. min-1. mL-1 in controls and 130.1 [78.9 to 230.3] nmol. min-1. mL-1 in MI patients [P<0.05]; concentration, 95.7 [73.2 to 135.5] microg/mL in controls and 35.4 [21.6 to 51.3] microg/mL in MI patients [P<0.001]). PON1-specific activity was significantly higher in patients with MI than in controls (1.5 [0.9 to 2.9] versus 3.4 [2.0 to 8.5] nmol. min-1. microg-1 [P<0.001]) due to the much lower PON1 concentration. PON1 activity had risen significantly (P<0.05) to 158.1 (85.4 to 282.0) nmol. min-1. mL-1 at day 42 but was still significantly less than that of controls. No significant variation in PON1 concentration occured in the days after MI or at 6 weeks. Also, no significant variation in specific activity was seen after MI. When the patients were divided into subgroups based on whether or not they received thrombolytic therapy on admission to hospital, no significant difference in PON1 levels was observed. Serum HDL cholesterol in patients with MI on admission was not significantly different than in controls, and the decrease that occurred by the fifth day after MI did not explain the lower PON1 levels. We conclude that low serum PON1 activity in patients with MI may be a consequence of the coronary event itself or could have been present before MI. The low PON1 activity was also not explicable on the basis of PON1 genotypes because the prevalence of genotypes associated with low activity was not sufficient to explain fully the difference in activity levels between patients and controls. The explanation for the low PON1 activity was most likely a decrease in serum PON1 concentration. The importance of PON1 as a predictive risk factor for MI should be assessed in future studies. PMID- 9974416 TI - Phenotype and genotype expression in pseudohomozygous factor VLEIDEN : the need for phenotype analysis. AB - The presence of a DNA mutation is frequently used to define a disease or a risk state. Because DNA typing has become easy and convenient in contrast to protein characterization, it is generally assumed that a mutation if present (or not) at the DNA level will be also present (or not) in the corresponding protein. However, discrepancies between phenotype and genotype can occur. A point mutation in the coagulation factor V gene (G1691-->A, resulting in an Arg506-->Gln amino acid substitution in the factor V molecule [factor VLEIDEN], leading to activated protein C resistance) is the most common genetic risk factor for familial thrombophilia. A pseudohomozygous factor VLEIDEN phenotype would occur if a heterozygous individual for factor VLEIDEN also did not express the "normal" (non Leiden) factor V allele. However, to date, no data have been available to confirm the presence of only the factor VLEIDEN form in the plasma of these individuals. Platelet mRNA from 2 presumed pseudohomozygous patients and their family members was isolated, the amplified partial cDNAs were sequenced or restricted, and the allelic bands were quantified. Both patients were found to be heterozygous for the G1691-->A substitution at both the DNA and mRNA levels. The presence of either the normal or mutated form of factor V in the patients' plasmas was investigated using a monoclonal antibody to factor V that recognizes an epitope located between residues 307 and 506 of the factor Va heavy chain. No normal factor V could be detected in the plasmas of the 2 propositi. The present data demonstrate absence of a correlation between genotype at position 1691 (at the DNA and mRNA levels) and the corresponding phenotype data found in the plasmas of patients with pseudohomozygous factor VLEIDEN. Overall, these data suggest the existence of heterogeneous genetic "lesions," which interfere with factor V expression, processing, secretion, and/or stability. Because the presence of the factor VLEIDEN molecule in plasma is directly related to pathology, identification and quantification of the circulating forms of factor V in plasma may be required for the diagnosis of individuals with activated protein C resistance. PMID- 9974417 TI - Glycoprotein IIb/IIIa antagonist FK633 could not prevent neointimal thickening in stent implantation model of canine coronary artery. AB - The platelet glycoprotein (GP) IIb/IIIa receptor antagonist appears to reduce the need for revascularization after coronary angioplasty. However, since the effect of GP IIb/IIIa receptor antagonist on the in-stent neointimal thickening has not been clarified, we examined it in the canine model. The beagle dogs were assigned to the control (n=7) or the GP IIb/IIIa receptor antagonist FK633 group (n=7). FK633 was administered by subcutaneous osmotic pumps (0.2 mg. kg-1. h-1) and an intravenous bolus injection (1 mg/kg) before stenting. A coil stent was implanted in the left circumflex coronary arteries. The platelet aggregation capability was significantly (<5%) and consistently reduced by FK633 except for the mild elevation (10% to 30%) on the next day of stenting. Hearts were excised 3 months after stent implantation. The area of intima and media and the area stenosis were obtained from the sections of the stented arteries. The area of intima and media and the area stenosis (1.3+/-0.2 mm2, 41.8+/-7.5% and 1.3+/-0.2 mm2, 33.9+/-6.7% in the FK633 and the control group, respectively) were not different between the groups. We conclude that, although GP IIb/IIIa antagonist FK633 prevented the platelet aggregation significantly and consistently, it could not prevent the neointimal thickening after stent implantation in canine coronary artery. PMID- 9974418 TI - Compound heterozygosity for an apolipoprotein A1 gene promoter mutation and a structural nonsense mutation with apolipoprotein A1 deficiency. AB - Apolipoprotein (apo) A1 plays a central role in the metabolism of HDL. We describe a novel genetic variant of the apoA1 gene identified in a patient with low concentrations of plasma HDL cholesterol. The proband, a 12-year-old Japanese boy, exhibited markedly low levels of both plasma apoA1 and HDL cholesterol. Genomic DNA sequencing of apoA1 genes of the patient showed a compound heterozygosity for an A to C substitution at 27 bp upstream of the transcription start site of 1 apoA1 allele, and a C to T substitution in another allele at residue 84 resulting in aberrant termination. The point mutation at nucleotide position -27 changed ATAAATA of the putative TATA box signal sequence to ATACATA. In addition to this mutation, the patient was heterozygous for a G to A substitution at position -75. Immunoblotting of an isoelectric focusing electrophoresis gel of the proband's plasma showed a trace amount of normal apoA1. No measurable plasma apoA1 and HDL cholesterol in a patient with homozygosity for nonsense mutation at residue 84 has been reported previously. To determine the effects of substitution either at position -27 or -75, plasmids containing the 5'-flanking region of the human apoA1 promoter fused to the CAT reporter gene were constructed and transfected in HepG2 cells. A construct with the A to C substitution at position -27 showed 41. 8+/-4.2%, and G to A substitution at position -75 showed 72.8+/-15. 2% (means+/-SD, n=3) of CAT activities, compared with the wild-type promoter sequence. A construct with the double substitutions at positions -27 and -75 showed only 22.8+/-1.3% (mean+/-SD, n=3) activity relative to the wild type. Our patient is the first case with a TATA box mutation etiologically related to lipoprotein disorders. PMID- 9974419 TI - Relationships of cerebral MRI findings to ultrasonographic carotid atherosclerosis in older adults : the Cardiovascular Health Study. CHS Collaborative Research Group. AB - Cerebral magnetic resonance imaging (MRI) has demonstrated a high prevalence of infarct-like lesions, white matter hyperintensities, and evidence of cerebral atrophy in older adults. While these findings are generally believed to be related to ischemia and atherosclerosis, their relationship to atherosclerosis in the carotid arteries remains to be explored. Study subjects were part of the multicenter Cardiovascular Health Study, a cross-sectional study of 3502 women and men >/=65 years of age undergoing cranial MRI and carotid ultrasonography. MRI infarcts were detected in 1068 participants (29.3%) and measurable carotid plaque in 2745 (75.3%). MRI infarcts, ventricular and sulcal widening, and white matter score were strongly associated with carotid intimal-medial thickness (IMT) and stenosis degree after adjustment for age and sex (all P<0. 01). Associations with plaque characteristics were less strong and less consistent; MRI infarcts were weakly associated only with surface irregularity, and ventricular size was weakly associated only with lesion density (both P<0.04). In contrast, sulcal widening was strongly related to plaque characteristics, with scores being higher in those with heterogeneous and irregular plaque (both P<0. 009). Adjustment for other risk factors, and for carotid IMT/stenosis, removed associations of MRI findings with plaque characteristics except for weak relationships remaining between MRI infarcts and surface irregularity and between sulcal score and heterogeneous plaque (both P<0.03). MRI abnormalities show strong and consistent relationships with increasing carotid IMT and stenosis degree but less strong associations with plaque characteristics, especially after adjusting for IMT and stenosis. PMID- 9974420 TI - Differential association of common carotid intima-media thickness and carotid atherosclerotic plaques with parental history of premature death from coronary heart disease : the EVA study. AB - Familial aggregation of coronary heart disease (CHD) has been reported in several studies. The specific underlying mechanisms and the relative contribution of atherosclerosis to the subsequent CHD events in subjects with family history are not well established. This study examined the association of parental history of premature death from CHD with ultrasound carotid measurements of atherosclerosis in a population of 1040 subjects aged 59 to 71 years. Ultrasound examination included measurements of intima-media thickness at the common carotid arteries (at sites free of plaques) and assessment of atherosclerotic plaques in the extracranial carotid arteries. Subjects who reported that 1 or both parents had sudden death or died of myocardial infarction before the age of 65 years were considered positive for parental history of premature death from CHD (n=53, 5.1%). The prevalence of atheromatous plaques was higher in subjects with history of premature death from CHD compared with those without history (41.5% versus 20.5%, P<0.001). Age- and sex-adjusted odds ratio of atheromatous plaques associated with parental history of premature death from CHD was 2.85 (95% confidence interval, 1.60 to 5.08; P<0.001). Multivariate adjustment for major known cardiovascular risk factors did not markedly alter the results (odds ratio, 2.70; P<0.002). In contrast, common carotid intima-media thickness was not associated with parental history of premature death from CHD (0.66+/-0.11 versus 0.66+/-0.12 mm, P=0.76). These findings were observed in both men and women. In conclusion, parental history of premature death from CHD is strongly associated with carotid plaques. Familial transmission of CHD risk does not seem to be specifically mediated by arterial wall thickening measured at sites free of plaques. PMID- 9974421 TI - Selectin blockade reduces neutrophil interaction with platelets at the site of deep arterial injury by angioplasty in pigs. AB - The adhesion of neutrophils to damaged arterial surfaces is increased in the presence of platelets by a mechanism implicating platelet P-selectin. Such interactions may enhance thrombus formation and the vascular response to injury. In this study, we investigated the effects of a selectin blocker (CY-1503), an analogue of sialyl Lewisx, on platelet and neutrophil interactions after arterial injury produced by angioplasty in pigs.51Cr-platelet deposition and 111In neutrophil adhesion were quantified on intact, mildly and deeply injured carotid arterial segments, produced by balloon dilation, in control (saline, n=8) and treated (CY-1503, 15 mg/kg IV, n=7) pigs. The hematological parameters, the aggregation of whole blood in response to adenosine diphosphate, and the activating clotting time, as well as the heart rate and mean arterial blood pressure, were similar among groups and were not influenced significantly by CY 1503. The level of platelet and neutrophil adhesion increased significantly with the severity of arterial injury but was not influenced by CY-1503 on intact and mildly injured arterial segments. However, at the site of deep arterial injury, CY-1503 treatment was associated with a 58% reduction (P<0.01) in neutrophil adhesion, from 446.7+/-72.6x10(3) neutrophils/cm2 in the control group to 186.8+/ 38.7x10(3) neutrophils/cm2 in the CY-1503-treated group, whereas platelet deposition remained unchanged (43.4+/-15.6x10(6) platelets/cm2 versus 50.1+/ 12.2x10(6) platelets/cm2 in the control group). In in vitro adhesion experiments, using isolated platelet and neutrophil suspensions, we found that CY-1503 interfered with the adhesion of neutrophils to damaged arterial surfaces only in the presence of platelets. In contact with thrombogenic arterial surfaces, adherent and activated platelets supports neutrophil adhesion at the site of deep injury by an adhesive interaction involving neutrophil sialyl Lewisx. The inhibitory effect of CY-1503 on neutrophil interaction with adherent platelets may be clinically relevant in patients undergoing percutaneous transluminal coronary angioplasty where platelet and neutrophil interactions may enhance the acute and chronic arterial response to injury. PMID- 9974423 TI - Cholesterol or triglyceride loading of human monocyte-derived macrophages by incubation with modified lipoproteins does not induce tissue factor expression. AB - Macrophages/foam cells localized in cholesterol- and triglyceride-rich regions of atherosclerotic plaques express high levels of tissue factor (TF), the essential cofactor and receptor of factor VIIa. It is not clear whether modified lipoproteins, for which several agonistic effects on macrophages have been described, are independent stimuli of TF expression in these cells. Therefore, we studied the effect of short-term (1 day) and long-term (4 to 7 days) incubation of human monocyte-derived macrophages cultured in suspension with modified and native LDLs or VLDLs on the expression of TF mRNA, antigen, and activity. We used native LDL or VLDL, moderately oxidized LDL or VLDL, severely oxidized LDL or VLDL, acetylated LDL, and beta-VLDL at a protein concentration of 100 microg/mL. Cholesterol loading occurred within 9 hours after the addition of acetylated LDL and continued during long-term incubation. Incubation of severely oxidized LDL for 7 days resulted in a slight increase in cholesterol content. Triglyceride loading was observed during short-term and long-term incubation with native and modified VLDLs. Neither cholesterol nor triglyceride loading resulted in expression of TF. Bacterial LPS still could induce TF expression in lipid-laden macrophages. Our results show that incubation with modified lipoproteins or lipid loading does not lead to TF expression in monocyte-derived macrophages cultured in suspension. This suggests that induction of TF expression in foam cells in the atherosclerotic lesion is triggered by additional or other components. PMID- 9974422 TI - Inhibition of arterial thrombus formation by ApoA1 Milano. AB - The mutant form of human apoA1, known as apoA1 Milano, is formed as a result of arginine 173 to cysteine substitution and inhibits experimental atherosclerosis in cholesterol-fed animals. This study was designed to determine if apoA1 Milano would modify arterial thrombogenesis. Sprague Dawley rats were intravenously administered the carrier alone (n=8) or apoA1 Milano (20 mg. kg-1. d-1 for 4 to 10 days, n=17). The abdominal cavity was opened, and the abdominal aorta was isolated. Whatman paper impregnated with 35% FeCl3 was wrapped around the surface of the aorta, and aortic flow was recorded continuously. In carrier-treated rats, an occlusive platelet-fibrin-rich thrombus was formed in 21.2+/-4.1 (mean+/-SD) minutes. Treatment of rats with apoA1 Milano markedly delayed time to thrombus formation (38.8+/-11.9 versus 21.2+/-4.1 minutes, P<0. 01), inhibited platelet aggregation (25+/-7% versus 50+/-11%, P<0. 01), and reduced weight of the thrombus (18.5+/-1.8 versus 23.7+/-2. 3 mg/cm, P<0.01). Total cholesterol and HDL levels remained similar in both groups of rats, but plasma apoA1 Milano levels were elevated in apoA1 Milano-treated rats. In in vitro studies, incubation of platelets with apoA1 Milano reduced ADP-induced platelet aggregation by about 50%, but apoA1 Milano had no direct effect on vasoreactivity. This study provides further evidence for critical role of platelets in thrombosis. Use of apoA1 Milano offers a novel approach to inhibit arterial thrombosis. PMID- 9974424 TI - Focal increases in vascular cell adhesion molecule-1 and intimal macrophages at atherosclerosis-susceptible sites in the rabbit aorta after short-term cholesterol feeding. AB - We tested the hypotheses that vascular cell adhesion molecule-1 (VCAM-1) expression on endothelium at lesion-prone sites in the rabbit aorta correlates with exposure to plasma cholesterol and that macrophage accumulation is associated with endothelial cells expressing VCAM-1. After rabbits were fed 0.25% cholesterol for 2 weeks, VCAM-1 expression was selectively increased at the distal and lateral portions of the major abdominal branches. In the arch and the celiac, superior mesenteric, and renal artery branches, VCAM-1 expression was positively correlated with the plasma cholesterol integrated over the duration of the experiments. After 2 weeks of cholesterol feeding, more macrophages were present around distal and lateral portions of the intercostal arteries and major abdominal branches relative to nonbranch regions. In the arch and around the intercostals and major abdominal branches, macrophage densities were positively correlated with the integrated plasma cholesterol. VCAM-1 and macrophage levels were correlated in lesion-prone regions. In normocholesterolemic rabbits, 23+/-4% (mean+/-SEM) of the macrophages were directly associated with VCAM-1-positive endothelium. After 2 weeks of 0.25% cholesterol feeding, the association increased to 37+/-4% (P<0.015). Associations were highest around the lateral and distal regions of the major abdominal branches. These results suggest that (1) VCAM-1 expression and intimal macrophage densities are influenced by plasma cholesterol and regional factors such as arterial fluid dynamics and (2) VCAM-1 plays a significant role in the localization of macrophages. PMID- 9974425 TI - Is the response of serum lipids and lipoproteins to postmenopausal hormone replacement therapy modified by ApoE genotype? AB - Postmenopausal hormone replacement therapy (HRT) has favorable effects on the serum lipid profile, and it also decreases the risk of cardiovascular diseases. The apolipoprotein E genotype has influence on serum levels of lipids and lipoproteins; apoE allele epsilon4 (apoE4) is associated with high total and LDL cholesterol levels. Genotype also influences the lipid responses to treatment with diet and statins, but the effect of HRT in different apoE genotypes is unknown. We studied the effects of HRT on the concentrations of serum lipids in apoE4-positive early postmenopausal women (genotypes 3/4 and 4/4) compared with apoE4-negative women (genotypes 2/3 and 3/3) in a population-based, prospective 5 year study. In all, 232 early postmenopausal women were randomized into 2 treatment groups: an HRT group (n=116), which received a sequential combination of 2 mg estradiol valerate (E2Val) from day 1 to 21 and 1 mg cyproterone acetate (CPA) from day 12 to 21 (Climen), and a placebo group (n=116), which received 500 mg/d calcium lactate. Serum concentrations of total, LDL, and HDL cholesterol and triglycerides were measured at baseline and after 2 and 5 years of treatment. A total of 154 women completed the final analysis. During the follow-up period, serum total cholesterol and LDL cholesterol concentrations decreased in the HRT group in apoE4-negative women (8.1% and 17.1%, respectively; P<0.001) but did not change in the HRT group in apoE4-positive women or in the placebo group. Serum HDL cholesterol concentrations decreased in the placebo group (apoE4-negative, 3.9%, P=0.015; apoE4-positive, 8.1%, P=0.004) but did not change significantly in the HRT group. Serum triglyceride levels tended to increase in both study groups and genotypes (15.1% to 36.2%, P<0.038 to 0.001), but no differences were observed between the study groups or genotypes, respectively. Our finding was that in postmenopausal Finnish women LDL cholesterol levels in apoE4-negative subjects respond more favorably to HRT than those in apoE4-positive subjects. This finding has potential importance in postmenopausal women with hypercholesterolemia, if confirmed in other studies. PMID- 9974426 TI - Analysis of LDL receptor gene mutations in Italian patients with homozygous familial hypercholesterolemia. AB - The aim of this study was the characterization of mutations of the LDL receptor gene in 39 Italian patients with homozygous familial hypercholesterolemia, who were examined during the period 1994 to 1996. The age of the patients ranged from 1 to 64 years; one third of them were older than 30. Plasma LDL cholesterol level ranged from 10.8 to 25.1 mmol/L. The residual LDL receptor activity, measured in cultured fibroblasts of 32 patients, varied from <2% to 30% of normal and was inversely correlated with the plasma LDL cholesterol level (r=-0.665; P<0.003). The most severe coronary atherosclerosis was observed in those patients with the lowest residual LDL receptor activity (0.10 in both women and men). However, there was significant evidence (P<0.10) that associations between variation in the probability of having CAC and variation in body mass index, plasma total cholesterol, and plasma ApoB in men and body mass index, plasma triglycerides, plasma ApoA1, and plasma ApoE in women were dependent on ApoE genotype. Thus, variation in the gene coding for ApoE may play a role in determining the contribution of established risk factors to risk of CAC. PMID- 9974429 TI - Large-artery elastic properties in young men : relationships to serum lipoproteins and oxidized low-density lipoproteins. AB - Measures of arterial elasticity have been proposed as surrogate markers for asymptomatic atherosclerosis. We investigated the relations of serum lipoproteins, oxidized low-density lipoprotein (ox-LDL), and familial hypercholesterolemia (FH) to arterial elasticity among young men. As a marker of arterial elasticity we measured compliance in the thoracic aorta by using magnetic resonance imaging and in the common carotid artery by using ultrasound. LDL diene conjugation was used as a marker of ox-LDL. In study I, 25 healthy men (aged 29 to 39) were classified into 2 extreme groups according to previously measured high-density lipoprotein cholesterol to total cholesterol ratio (HDL C/TC ratio). In study II, the healthy men were used as controls for 10 age matched asymptomatic patients with FH. In healthy men, the group with low HDL C/TC ratio had decreased carotid artery compliance (2. 3+/-0.4% versus 1.9+/ 0.5%/10 mm Hg, P=0.034). In univariate analysis, the compliance of the carotid artery associated with ox-LDL (r =-0.49, P=0.016) and HDL-C/TC ratio (r=0.41, P=0.040). In multivariate regression analyses, ox-LDL was the only independent determinant for compliance of the carotid artery (P=0.016). Aortic elasticity was not related to standard lipid variables, but the compliance of the ascending aorta associated with ox-LDL (r=-0.44, P=0.030). In FH patients, arterial elasticity was similar to that in controls. We conclude that elasticity of the common carotid artery is affected by serum lipid profile in young men. The current study demonstrates for the first time an in vivo association between ox LDL and arterial elasticity suggesting that oxidative modification of LDL may play a role in the alteration of arterial wall elastic properties. PMID- 9974430 TI - Quantitative trait locus analysis of plasma lipoprotein levels in an autoimmune mouse model : interactions between lipoprotein metabolism, autoimmune disease, and atherogenesis. AB - The autoimmune MRL/lpr mouse strain, a model for systemic lupus erythematosus, exhibited an unusual plasma lipoprotein profile, suggesting a possible interaction of autoimmune disease and lipoprotein metabolism. In an effort to examine the genetic basis of such interactions, and to study their relationship to atherogenesis, we performed a quantitative trait locus analysis using a total of 272 (MRL/lprxBALB/cJ) second generation (F2) intercross mice. These mice were examined for levels of total plasma cholesterol, HDL cholesterol, VLDL and LDL cholesterol, unesterified cholesterol, autoantibodies, and aortic fatty streak lesions. Using a genome scan approach, we identified 4 quantitative trait loci controlling plasma lipoprotein levels on chromosomes (Chrs) 5, 8, 15, and 19. The locus on Chr 15 exhibited lod scores of 11.1 for total cholesterol and 6.7 for VLDL and LDL cholesterol in mice fed an atherogenic diet, and it contains a candidate gene, the sterol regulatory element binding protein-2. The locus on Chr 5 exhibited lod scores of 3.8 for total cholesterol and 4.1 for unesterified cholesterol in mice fed an atherogenic diet, and this locus has been observed in 2 previous studies. The locus on Chr 8 exhibited a lod score of 3.1 for unesterified cholesterol in mice fed a chow diet. This locus contains the lecithin-cholesterol acyltransferase gene, and decreased activity of the enzyme in the MRL strain suggests that this gene underlies the quantitative-trait locus. The locus on Chr 19 exhibited a lod score of 8.4 for HDL cholesterol and includes the Fas gene, which is mutated in MRL/lpr mice and is primarily responsible for the autoimmune phenotype in this cross. That the Fas gene is responsible for the HDL quantitative-trait loci is supported by the finding that autoantibody levels were strongly correlated with HDL cholesterol levels (rho=-0.37, P<0.0001) among the F2 mice. HDL cholesterol levels were in turn significantly associated with aortic fatty streak lesions among the F2 mice (rho=-0.17, P=0.006). Further, there was a threshold effect of autoantibody levels on the development of fatty streak lesions (rho=0.45, P=0.004 for 42 F2 mice with anti-dsDNA Ab over 0.5 OD). Our results support the concept that the high prevalence of coronary artery disease in systemic lupus erythematosus is due in part to a reduction of HDL cholesterol levels resulting from the autoimmune disease. PMID- 9974431 TI - Gene polymorphism of t-PA is associated with forearm vascular release rate of t PA. AB - We have observed marked interindividual differences in release rates of tissue type plasminogen activator (t-PA) among healthy subjects. The objective of the current study was to test the hypothesis that there is an association between a genetic variation at the t-PA locus and the in vivo release rate of t-PA. Fifty one healthy males were studied at rest in the morning and 27 of these were also subjected to a mental stress test. Net release rates of total t-PA across the forearm vascular bed were calculated as the product of the venoarterial concentration gradient and forearm plasma flow. Zygosity for an Alu-repeat polymorphism in intron 8 of the t-PA gene was determined by a polymerase chain reaction. Basal t-PA release rates differed markedly by genotype (ANOVA, P<0.05); subjects homozygous for the insertion had a significantly higher release rate (mean 10.9 ng. min-1. L-1, n=19) than both heterozygotes (4.5 ng. min-1. L-1, n=26) and subjects homozygous for the deletion (0.9 ng. min-1. L-1, n=6). After 2 minutes of mental stress release rates had increased approximately 2-fold in all groups. Arterial and venous plasma levels of t-PA were unrelated to genotype. In conclusion, the current results provide the first evidence of an association between a common genetic variation at the t-PA locus and interindividual differences in net release rates of t-PA in vivo. The relationship is not reflected by circulating steady-state plasma levels and can thus not be disclosed by conventional venous plasma sampling. PMID- 9974432 TI - Renal transplantation from living donors. PMID- 9974433 TI - Delivering inhaled corticosteroids to patients. PMID- 9974434 TI - Radiosurgery for brain tumours. PMID- 9974435 TI - Points for pain: waiting list priority scoring systems. PMID- 9974436 TI - Breast implants: evidence based patient choice and litigation. PMID- 9974438 TI - Educated adults have fewer sex problems in the US PMID- 9974439 TI - In brief PMID- 9974437 TI - Antiabortionists ordered to pay $108m for threats of violence. PMID- 9974441 TI - NICE to sort clinical "wheat from chaff" PMID- 9974440 TI - US medical association reaches agreement with sacked editor. PMID- 9974442 TI - Antibiotics may prevent heart attacks PMID- 9974444 TI - Rush for primary care groups PMID- 9974443 TI - Advertising standards authority finds against Nestle. PMID- 9974445 TI - US debates treatment of marginally viable babies. PMID- 9974446 TI - European court upholds UK ban on Halcion. PMID- 9974447 TI - Edinburgh university fined forlack of safety checks PMID- 9974448 TI - Consultant physicians should be appraised annually PMID- 9974449 TI - Former French ministers on trial over blood. PMID- 9974450 TI - Spain cuts waiting times for surgery. PMID- 9974451 TI - Mild cervical dysplasia often reverts to normal PMID- 9974452 TI - UN study reports Asian economic crisis has hit women's health. PMID- 9974453 TI - Testicular cancer increases in ontario PMID- 9974454 TI - Prenatal and perinatal risk factors for schizophrenia, affective psychosis, and reactive psychosis of early onset: case-control study. AB - OBJECTIVE: To examine prenatal and perinatal risk factors for subsequent development of schizophrenia and affective and reactive psychosis. DESIGN: Three population based, case-control studies conducted within a Sweden-wide cohort of all children born during 1973-9. This was done by linking individual data from the Swedish birth register, which represents 99% of all births in Sweden, to the Swedish inpatient register. SUBJECTS: Patients listed in inpatient register as having been first admitted to hospital aged 15-21 years with a main diagnosis of schizophrenia (n=167), affective psychosis (n=198), or reactive psychosis (n=292). For each case, five controls were selected. MAIN OUTCOME MEASURES: Risks of schizophrenia and affective and reactive psychosis in relation to pregnancy and perinatal characteristics. RESULTS: Schizophrenia was positively associated with multiparity (odds ratio 2.0), maternal bleeding during pregnancy (odds ratio 3.5), and birth in late winter (odds ratio 1.4). Affective psychosis was associated with uterine atony (odds ratio 2.2) and late winter birth (odds ratio 1.5). Reactive psychosis was related to multiparity (odds ratio 2.1). An increased risk for schizophrenia was found in boys who were small for their gestational age at birth (odds ratio 3.2), who were number four or more in birth order (odds ratio 3.6), and whose mothers had had bleeding during late pregnancy (odds ratio 4.0). CONCLUSIONS: A few specific pregnancy and perinatal factors were associated with the subsequent development of psychotic disorder, particularly schizophrenia, in early adult life. The association of small size for gestational age and bleeding during pregnancy with increased risk of early onset schizophrenia among males could reflect placental insufficiency. PMID- 9974455 TI - Catch-up growth in childhood and death from coronary heart disease: longitudinal study. AB - OBJECTIVE: To examine whether catch-up growth during childhood modifies the increased risk of death from coronary heart disease that is associated with reduced intrauterine growth. DESIGN: Follow up study of men whose body size at birth was recorded and who had an average of 10 measurements taken of their height and weight through childhood. SETTING: Helsinki, Finland. SUBJECTS: 3641 men who were born in Helsinki University Central Hospital during 1924-33 and who went to school in Helsinki. MAIN OUTCOME MEASURES: Hazard ratios for death from coronary heart disease. RESULTS: Death from coronary heart disease was associated with low birth weight and, more strongly, with a low ponderal index at birth. Men who died from coronary heart disease had an above average body mass index at all ages from 7 to 15 years. In a simultaneous regression the hazard ratio for death from the disease increased by 14% (95% confidence interval 8% to 19%; P<0.0001) for each unit (kg/m3) decrease in ponderal index at birth and by 22% (10% to 36%; P=0.0001) for each unit (kg/m2) increase in body mass index at 11 years of age. Body mass index in childhood was strongly related to maternal body mass index, which in turn was related to coronary heart disease. The extent of crowding in the home during childhood, although related to body mass index in childhood, was not related to later coronary heart disease. CONCLUSION: The highest death rates from coronary heart disease occurred in boys who were thin at birth but whose weight caught up so that they had an average or above average body mass from the age of 7 years. Death from coronary heart disease may be a consequence of poor prenatal nutrition followed by improved postnatal nutrition. PMID- 9974456 TI - Follow up study of longstanding depression as predictor of mortality in elderly people living in the community. PMID- 9974457 TI - Historical cohort study of in utero exposure to uterotonic drugs and cognitive function in young adult life. PMID- 9974459 TI - What is research? PMID- 9974458 TI - Giant cell arteritis and thyroid dysfunction: multicentre case-control study. The Groupe de Recherche sur l'Arteritea Cellules Geantes. PMID- 9974460 TI - A half mixed compound? PMID- 9974461 TI - Cross sectional study of symptom attribution and recognition of depression and anxiety in primary care. AB - OBJECTIVES: To examine the effect of patients' causal attributions of common somatic symptoms on recognition by general practitioners of cases of depression and anxiety and to test the hypothesis that normalising attributions make recognition less likely. DESIGN: Cross sectional survey. SETTING: One general practice of eight doctors in Bristol. SUBJECTS: 305 general practice attenders. MAIN OUTCOME MEASURE: The rate of detection by general practitioners of cases of depression and anxiety as defined by the general health questionnaire. RESULTS: Consecutive attenders completed the general health questionnaire and the symptom interpretation questionnaire, which scores style of symptom attribution along the dimensions of psychologising, somatising, and normalising. General practitioners detected depression or anxiety in 56 (36%; 95% confidence interval 28% to 44%) of the 157 patients who scored highly on the general health questionnaire. Subjects with a normalising attributional style were less likely to be detected as cases; doctors did not make any psychological diagnosis in 46 (85%; 73% to 93%) of 54 patients who had high questionnaire and high normalising scores. Those with a psychologising style were more likely to be detected; doctors did not detect 21 (38%; 25% to 52%) of 55 patients who had high questionnaire and high psychologising scores. The somatisation scale was not associated with low detection rates. This pattern of results persisted after adjustment for age, sex, general health questionnaire score, and general practitioner. CONCLUSIONS: Normalising attributions minimise symptoms and are non-pathological in character. The normalising attributional style is predominant in general practice attenders and is an important cause of low rates of detection of depression and anxiety. PMID- 9974462 TI - Experiences with "rapid appraisal" in primary care: involving the public in assessing health needs, orientating staff, and educating medical students. PMID- 9974465 TI - The inventor of matches PMID- 9974463 TI - Recent advances: oncology. PMID- 9974464 TI - Haemochromatosis and exercise related joint pains. PMID- 9974466 TI - ABC of sexual health: homosexual men and women. PMID- 9974467 TI - High altitude medicine PMID- 9974469 TI - The plague returns PMID- 9974468 TI - Perspectives of commissioners and cancer specialists in prioritising new cancer drugs: impact of the evidence threshold. PMID- 9974470 TI - Meta-analysis of diabetes care in general practice. All glucose meters must be subject to formal quality control measures. PMID- 9974471 TI - Evidence based patient information. Doctors should be encouraged to develop information resources on the internet. PMID- 9974472 TI - Diagnosing serious child abuse. Death from Munchausen syndrome by proxy is overestimated. PMID- 9974473 TI - Vitamin B-6. Many have found relief from disorders for which no effective treatment exists. PMID- 9974474 TI - Albumin controversy continues. Meta-analysis has affected use of albumin. PMID- 9974476 TI - Labour's health policy is having paradoxical effect in Iberian countries. PMID- 9974475 TI - Beyond conflict of interest. What is truth as it relates to albumin? PMID- 9974477 TI - Early regrafting after primary liver transplantation carries increased risk of death. PMID- 9974479 TI - William james archibald craig PMID- 9974478 TI - Community health services must be considered in proposals for integrated records. PMID- 9974486 TI - The emperor has no clothes on PMID- 9974487 TI - Snow in chicago PMID- 9974488 TI - Early life and adult disease PMID- 9974489 TI - Adverse prenatal and perinatal factors are associated with schizophrenia of early onset PMID- 9974490 TI - Catch-up growth in childhood is linked with increased risk of coronary heart disease PMID- 9974491 TI - Depression may be missed in patients who "normalise" their symptoms PMID- 9974492 TI - Longstanding depression, but not recovery from depression, predicts mortality in old people PMID- 9974493 TI - Uterotonic drugs have no adverse effects on cognitive function PMID- 9974494 TI - Thyroid dysfunction is not more common in people with giant cell ateritis PMID- 9974495 TI - Sedation for pediatric imaging studies. AB - This article discusses safe sedation for pediatric imaging. Emphasis is placed upon implementation of an institutional sedation program according to guidelines of the American Academy of Pediatrics. Standards for patient assessment and preparation, sedative administration, monitoring, and discharge are reviewed. A comparison of available sedative agents is also provided. PMID- 9974496 TI - Transcranial Doppler in the newborn with asphyxia. AB - Transcranial Doppler of infants suffering hypoxia-ischemia may demonstrate high diastolic flow in the early postasphyxial and hyperemic phase of the insult. This increase in diastolic flow decreases the resistive index. The use of the resistive index to quickly assess the infant at the bedside may become more important with the advent of newer neuroprotective strategies. PMID- 9974497 TI - Transcranial Doppler imaging in pediatric abnormalities in older children. AB - Transcranial Doppler (TCD) is a noninvasive diagnostic ultrasound study which uses a 2 megahertz pulsed Doppler transducer to measure the velocity and pulsatility of blood flow within the major intracranial arteries. It has proved to be extremely useful as a screening test or to help confirm the diagnosis of several clinical conditions in infants and children. Some of the proved indications for TCD is for evaluating cerebrovascular occlusive disease especially in screening children with sickle cell disease, hydrocephalus, asphyxia and cerebral edema, confirming brain death, arteriovenous malformations, and vasoplasm. TCD technique, indications, and common pathological findings are emphasized. PMID- 9974498 TI - Diffusion imaging in pediatric hypoxic ischemia injury. AB - This article is a brief review on the physics of diffusion imaging as well as the pertinent adult literature regarding stroke and diffusion imaging. The remainder of the article focuses on the potential uses of diffusion imaging for the evaluation of hypoxic ischemia injury in pediatric populations. In particular, diffusion changes in hypoxic ischemia injury in newborns are reviewed as the diffusion abnormalities in immature brain may behave in a manner different from adults. PMID- 9974499 TI - Disorders of cortical formation: radiologic-pathologic correlation. AB - The advent of newer imaging techniques, such as high resolution MR imaging and surface reconstructions of 3-dimensional data sets, has led to a greater in-vivo understanding of cortical malformations of the brain. The disorders of cortical formation are illustrated with routine imaging, surface reconstruction, and pathologic specimens. PMID- 9974500 TI - Hydrocephalus in children: neurosurgical and neuroimaging concerns. AB - The neuroimaging of hydrocephalus from the perspective of the pediatric neurosurgeon is discussed. Processes with new developments in therapy and imaging are described, including congenital causes of hydrocephalus, unilateral hydrocephalus, trapped fourth ventricle, and benign external hydrocephalus. PMID- 9974501 TI - Imaging of the pediatric orbit and visual pathways: computed tomography and magnetic resonance imaging. AB - Techniques for pediatric MR imaging and computed tomography and anatomy of the orbit and intracranial visual pathways are presented and reviewed in this article. Imaging findings are presented for the following categories of abnormality: a) orbital anomalies related to congenital disorders of the brain, b) disorders of the orbit (ocular, nonocular, or multicompartmental), c) disorders of the intracranial visual pathways (suprasellar cistern, optic radiations, or occipital cortex), and d) disorders of gaze (extraocular muscles, cranial nerves, and brainstem). Careful assessment of the clinical findings, anatomic location of the visual impairment, and familiarity with disorders that often affect pediatric patients are helpful in guiding neuroimaging evaluation of the child with ocular, orbital, or central patterns of visual disturbance. PMID- 9974502 TI - Head and neck vascular anomalies of childhood. AB - Vascular anomalies of the head and neck are common lesions of childhood. The vascular anomalies can be divided into hemangiomas and vascular malformations. Each of these lesions has a characteristic imaging appearance. Correctly classifying the anomaly is essential in directing the treatment of these lesions. PMID- 9974503 TI - Imaging of pediatric temporal bone abnormalities. AB - Disorders involving the temporal bone in children may be associated with considerable morbidity. Hearing loss occurring during childhood may impair cognitive development and should therefore be diagnosed and treated as soon as possible. Thin section high resolution CT and MR imaging of the temporal bone provide critical information about a variety of developmental, inflammatory, traumatic, and neoplastic disorders, and are used for diagnostic purposes and to help determine therapeutic options. PMID- 9974504 TI - Imaging of neuroendocrine disorders of childhood. AB - This article focuses on the neuroendocrine disorders of childhood. The commonly associated neuroradiologic abnormalities of the hypothalamic-pituitary axis are covered in detail. PMID- 9974505 TI - Imaging the central nervous system effects of radiation and chemotherapy of pediatric tumors. AB - New developments in radiotherapy and chemotherapy have resulted in significant improvements in survival from childhood tumors. Stereotactic radiosurgery and other conformed field radiotherapy treatments allow precise localization of tumors. Through small beam sizes, these new radiation techniques deliver steep dose gradients at the field edges permitting the prescribed dose to be given to the tumor while avoiding vital structures only millimeters away. Newer chemotherapy regimens allow radiotherapy to be postponed until the child's brain can better tolerate radiation. The MR imaging and CT scans appearance of treated childhood brain tumors and the new developments in radiation and chemotherapy are discussed. PMID- 9974506 TI - Neuroimaging of scoliosis in childhood. AB - A curvature abnormality may be the initial or major presenting feature in a child with disease of the spinal column or spinal neuraxis. A simplified classification of common spinal curvature abnormalities of childhood include idiopathic, congenital/dysraphic, skeletal dysplasia, neurofibromatosis, and painful. The great majority of childhood scoliosis falls into the idiopathic category. Atypical clinical or radiographic features in a presumed idiopathic scoliosis may indicate an otherwise occult tumor or hydrosyringomyelia, or may be a consequence of increasing curvature with disk protrusion, nerve impingement, or cord attenuation. Neuroimaging beyond plain films is commonly necessary for atypical idiopathic scoliosis and for the other categories of scoliosis listed. PMID- 9974508 TI - Calculation of effective elastic moduli of polycrystalline materials including nontextured samples and fiber textures. PMID- 9974507 TI - Local-density studies of the structure and electronic properties of B and S in an Fe grain boundary. PMID- 9974509 TI - Mechanical degradation and viscous dissipation in B2O3. PMID- 9974510 TI - Criticality in the plastic deformation of L12 intermetallic compounds. PMID- 9974511 TI - Quantum-interference asymmetries in the multiphoton radio-frequency sideband spectra of 57Fe. PMID- 9974512 TI - Thermodynamics of nucleation in current-carrying conductors. PMID- 9974513 TI - Computer simulation of domain formation in the order-disorder phase transition of the KSCN model. PMID- 9974515 TI - Nature of phosphorus embrittlement of the Fe Sigma 3 PMID- 9974514 TI - Exciton energy and its pressure dependence in alkali halides. PMID- 9974517 TI - Transport and scattering mean free paths of classical waves. PMID- 9974516 TI - Evolution of precipitates in lead-implanted aluminum: A backscattering and channeling study. PMID- 9974518 TI - Medium-range interactions and structural complexity in aluminum-based intermetallic compounds. PMID- 9974519 TI - Relation between the beta and rapidly quenched liquid phases of gallium. PMID- 9974520 TI - Anomalies in the liquid structure of Ga metal. PMID- 9974521 TI - Thermodynamics and structure of liquid binary alloys calculated using an analytic pair potential. PMID- 9974522 TI - Structural transformation in densified silica glass: A molecular-dynamics study. PMID- 9974523 TI - Reflection spectra of dense amorphous SiO2 in the vacuum-uv region. PMID- 9974524 TI - Loop algorithms for quantum simulations of fermion models on lattices. PMID- 9974525 TI - Electronic-Raman-scattering study of the low-lying energy levels of trivalent cerium-doped yttria. PMID- 9974526 TI - Independent determination of local grain boundary and pumping diffusion coefficients. PMID- 9974528 TI - Measurement of the acoustic-phonon mean free path in a free-standing metal film. PMID- 9974527 TI - Variational calculation for large bipolarons in the strong-coupling limit. PMID- 9974530 TI - Ferromagnetic-resonance studies of granular giant-magnetoresistive materials. PMID- 9974529 TI - Observation and assignment of silent and higher-order vibrations in the infrared transmission of C60 crystals. PMID- 9974531 TI - Magnetic excitations in the dilute anisotropic antiferromagnet FexZn1-xF2. PMID- 9974532 TI - Antiferromagnetic coupling in (111)-oriented Co/Pt superlattices. PMID- 9974533 TI - Magnetic phase transition of stage-2 CucCo1-cCl2-graphite intercalation compounds. PMID- 9974534 TI - Physical properties of rare-earth metal-ion vermiculite intercalation compounds. PMID- 9974535 TI - Magnetic form factor for itinerant-electron systems. PMID- 9974536 TI - Model calculation of the crystal-field magnetostriction and its temperature dependence in the itinerant uniaxial ferromagnet Y2Fe17. PMID- 9974537 TI - Anisotropic Heisenberg antiferromagnet in the presence of a magnetic field for arbitrary dimension and spin. PMID- 9974539 TI - Spin-gap fixed points in the double-chain problem. PMID- 9974538 TI - Kondo and crystal-field effects in the compound YbPtGa. PMID- 9974541 TI - Magnetic multilayers with (Nb,Mo,Cr) spacer materials. PMID- 9974540 TI - Finite-temperature properties of quantum antiferromagnets in a uniform magnetic field in one and two dimensions. PMID- 9974542 TI - Spin fluctuations in gamma -Fe and in Fe3Pt Invar from local-density-functional calculations. PMID- 9974544 TI - Gapless phases in an S=1/2 quantum spin chain with bond alternation. PMID- 9974543 TI - Relaxation of degenerate crystal-field excitations in cubic metals. PMID- 9974545 TI - Flux flow of Abrikosov vortices in type-II superconductors. PMID- 9974546 TI - Superconductor-normal-metal-superconductor junction in a strong magnetic field. PMID- 9974548 TI - Spin-wave velocity, entropy, and magnetization in bcc solid 3He. PMID- 9974547 TI - Interaction between mixed-valent rare-earth impurities in BCS superconductors. PMID- 9974549 TI - Vortices in two-dimensional superconducting weakly coupled wire networks. PMID- 9974551 TI - Magnetoelastic theory of type-II superconductors in the mixed state. PMID- 9974550 TI - Superconductivity at 15 K in the metastable ScNi2B2C compound. PMID- 9974552 TI - Phase transitions in an interacting boson model with near-neighbor repulsion. PMID- 9974553 TI - Conductance regimes in superconducting junctions of atomic size. PMID- 9974554 TI - Singlet pairing in the double-chain t-J model. PMID- 9974556 TI - Cooper-pair current through ultrasmall Josephson junctions. PMID- 9974555 TI - Weak-localization and Maki-Thompson superconducting fluctuation effects in crystalline disordered Ti-Al-(Sn,Co) alloys at T>Tc. PMID- 9974557 TI - Conserving approximations for the attractive Holstein and Hubbard models. PMID- 9974558 TI - Correlated squeezed-state approach for the ground state of a system with strong electron-phonon interaction. PMID- 9974559 TI - Charge-carrier density and interplane coupling in Y2Ba4Cu7O15: A Cu NMR-NQR study. PMID- 9974561 TI - Optical conductivity of the Hubbard model at finite temperature. PMID- 9974560 TI - Spin-gap formation in bilayer cuprates due to enhanced interlayer pairing. PMID- 9974562 TI - Dynamic Cooper-pair breaking by tunnel injection of quasiparticles into a high-Tc YBa2Cu3O7 superconductor. PMID- 9974563 TI - Resistivity, magnetic-susceptibility, and specific-heat studies of ErBa2(Cu(1 x)Mx)3O7-y PMID- 9974564 TI - Vortex depinning frequency in YBa2Cu3O7-x superconducting thin films: Anisotropy and temperature dependence. PMID- 9974565 TI - Explanation of the dissipation observed in several high-temperature superconductors using a modified Ambegaokar-Halperin model. PMID- 9974566 TI - Microwave response of anisotropic high-temperature-superconductor crystals. PMID- 9974567 TI - Anisotropic resistivity of Bi2Sr2CuOx crystals. PMID- 9974568 TI - Magneto-optical measurements of the surface step of magnetic induction in YBa2Cu3O7 single crystals: Direct evidence of the influence of the surface barrier. PMID- 9974570 TI - Anisotropy of the magnetic properties of c-axis-aligned HgBa2Ca2Cu3O8+ delta powders. PMID- 9974569 TI - Ginzburg-Landau theory of fluctuation magnetization of two-dimensional superconductors. PMID- 9974571 TI - Electrodynamics of Nd1.85Ce0.15CuO4: Comparison with Nb and YBa2Cu3O7- delta. PMID- 9974572 TI - Critical behavior of phase transitions in potassium-dihydrogen-phosphate-type ferroelectrics. PMID- 9974573 TI - Implantation-induced structural changes in evaporated amorphous Ge. PMID- 9974574 TI - Thermal conductivity of solid nitrogen. PMID- 9974576 TI - Raman-active phonons of the spin-1 chain antiferromagnets R2BaNiO5 (R=Gd and Y). PMID- 9974575 TI - Mesoscopic spin tunneling in the hard-random-axis-magnet amorphous alloy Tb2Fe. PMID- 9974577 TI - Edge states in antiferromagnetic quantum spin chains. PMID- 9974578 TI - Phase diagram of the Ashkin-Teller quantum spin chain. PMID- 9974579 TI - Anomalous phase transition in URu2Si2. PMID- 9974581 TI - Flux flow and flux cutting in type-II superconductors carrying a longitudinal current. PMID- 9974580 TI - Direct measurement of single-vortex diameters by electron holography. PMID- 9974582 TI - Phase diagram of the extended attractive Hubbard model in one dimension. PMID- 9974584 TI - Influence of magnetic imperfections on the low-temperature properties of d-wave superconductors. PMID- 9974583 TI - Capacity of a pinning site for trapping quantized vortices in superfluid 4He. PMID- 9974585 TI - Raman scattering from YBa2Fe3O8+ delta. PMID- 9974587 TI - Role of Ca in enhancing the superconductivity of YBa2Cu3O7-y. PMID- 9974586 TI - Superconducting gap and order parameter in Bi2Sr2CaCu2O8+x. PMID- 9974589 TI - Dielectric spectroscopy in SrTiO3. PMID- 9974588 TI - Anomalous helium-bubble growth in palladium. PMID- 9974590 TI - Dynamics of polybutadiene above the glass transition studied by Brillouin light scattering. PMID- 9974592 TI - Large Fermi surface of the one-dimensional Kondo lattice model. PMID- 9974591 TI - Valence states of Sm in SmRuSn3. PMID- 9974593 TI - Evidence for nuclear multiphoton transitions in 57Fe based on radio-frequency sidebands to the forbidden hyperfine components of the 14.4-keV transition. PMID- 9974594 TI - Ultrasmall-moment static magnetism in CeRu2Si2. PMID- 9974595 TI - Anisotropic physical properties of the Kondo semiconductor CeRhSb. PMID- 9974596 TI - Combined Josephson and charging behavior of the supercurrent in the superconducting single-electron transistor. PMID- 9974597 TI - Andreev reflection in nanoscale metal-superconductor devices. PMID- 9974598 TI - Spin gap and superconductivity in the three-dimensional attractive Hubbard model. PMID- 9974599 TI - Irradiation-induced crossover from point defects to correlated disorder pinning in Bi2Sr2CaCu2Ox single crystals. PMID- 9974600 TI - Far-infrared transmission of Ba1-xKxBiO3 thin films. PMID- 9974602 TI - 199Hg Knight shift and spin-lattice relaxation in HgBa2CuO4+ delta. PMID- 9974601 TI - Competition between magnetism and superconductivity in rare-earth nickel boride carbides. PMID- 9974603 TI - Spin-charge separation in the two-dimensional Hubbard and t-J models at low electronic density. PMID- 9974605 TI - X-ray-absorption studies of the d-orbital occupancies of selected 4d/5d transition metals compounded with group-III/IV ligands. PMID- 9974604 TI - Erratum: Electron-paramagnetic-resonance study of transition-metal-doped BaTiO3: Effect of material processing on Fermi-level position PMID- 9974606 TI - Luminescence of the self-trapped exciton in KI under pressure. PMID- 9974607 TI - Tetragonal distortion and structural stability of indium at high pressures. PMID- 9974608 TI - Grain-boundary melting: A Monte Carlo study. PMID- 9974610 TI - Thermal conductivity of the Ih and XI phases of ice. PMID- 9974609 TI - High-pressure resistance study of NpSb up to 23 GPa. PMID- 9974611 TI - Temperature dependence of cross-relaxation processes in Pr3+-doped yttrium aluminum garnet. PMID- 9974613 TI - Intermediate 4f bonding structure for samarium under pressure. PMID- 9974612 TI - Multiple-scattering analysis of NEXAFS spectra of molecular oxygen anions in differently grown cesium oxides. PMID- 9974614 TI - Measurement of up-conversion energy-transfer probabilities in Ho:Y3Al5O12 and Tm:Y3Al5O12. PMID- 9974615 TI - Theory of second-harmonic generation from atom pairs in solids. PMID- 9974616 TI - Unequal wave vectors in short- versus long-range ordering in intermetallic compounds. PMID- 9974617 TI - Proton-glass dielectric behavior and phase diagram of Cs1-x(NH4)xH2AsO4. PMID- 9974619 TI - X-ray-absorption spectroscopy of a Nd3+-exchanged beta "-alumina crystal. PMID- 9974618 TI - First-principles simulated-annealing study of phase transitions and short-range order in transition-metal and semiconductor alloys. PMID- 9974620 TI - K-shell ionization under zone-axis electron-diffraction conditions. PMID- 9974621 TI - Nonequilibrium dielectric behavior in glasses at low temperatures: Evidence for interacting defects. PMID- 9974622 TI - Electronic structure of icosahedral Al70Pd20Mn10. PMID- 9974624 TI - Variational approach to the quantum lattice fluctuations in the Su-Schrieffer Heeger model: The ground state. PMID- 9974623 TI - Structural properties of amorphous hydrogenated carbon. IV. A molecular-dynamics investigation and comparison to experiments. PMID- 9974625 TI - Momentum distributions and final-state effects in neutron scattering. PMID- 9974626 TI - Dynamical properties and related optical spectra of fullerenes: The bond-charge model description. PMID- 9974627 TI - Chaotic motion of diffuse domain walls in magnetic garnets. PMID- 9974629 TI - Spin-spin correlations in a finite-sized spherical model under twisted boundary conditions. PMID- 9974628 TI - Spectroscopic properties of Cr3+ ions at the defect sites in cubic fluoroperovskite crystals. PMID- 9974630 TI - Spin-polarized photoelectron diffraction using circularly polarized x rays. PMID- 9974631 TI - Periodic diamagnetic domain structures in metals under a quantizing magnetic field. PMID- 9974632 TI - Magnetic ordering in U2Pd2In and U2Pd2Sn. PMID- 9974633 TI - Effects of vacancies in the triangular spin-1/2 antiferromagnet. PMID- 9974634 TI - Oblique-incidence far-infrared reflectivity study of the uniaxial antiferromagnet FeF2. PMID- 9974635 TI - Susceptibility and excitation spectrum of (VO)2P2O7 in ladder and dimer-chain models. PMID- 9974636 TI - Flux measurements on ferromagnetic microprobes by electron holography. PMID- 9974637 TI - General spin-3/2 Ising model in a honeycomb lattice: Exactly solvable case. PMID- 9974639 TI - Schwinger-boson mean-field theory for the two-dimensional antiferromagnetic Heisenberg model with a square lattice. PMID- 9974638 TI - gamma -ray polarization in transmission through a noncubic and nonmagnetic single crystal. PMID- 9974640 TI - Static chaos and scaling behavior in the spin-glass phase. PMID- 9974641 TI - Finite-size scaling of the frustrated Heisenberg model on a hexagonal lattice. PMID- 9974643 TI - Magnetoresistance and magnetization studies of the Laves-phase compound Ce(Fe0.92Al0.08)2. PMID- 9974642 TI - Crossover in the specific heat of dilute magnets induced by critical spin-wave dynamics. PMID- 9974644 TI - Spin-1/2 Heisenberg antiferromagnet on the kagome-acute lattice: High-temperature expansion and exact-diagonalization studies. PMID- 9974645 TI - Spin-wave stiffness of the Heisenberg antiferromagnet at zero temperature. PMID- 9974646 TI - Dynamical T=0 correlations of the S=1/2 one-dimensional Heisenberg antiferromagnet with 1/r2 exchange in a magnetic field. PMID- 9974648 TI - Orbitally degenerate spin-fluctuation model for heavy-fermion superconductivity. PMID- 9974647 TI - Particle excitations in the anyon gas at zero and finite temperature. PMID- 9974650 TI - Integral-equation approach for the Bean critical-state model in demagnetizing and nonuniform-field geometries. PMID- 9974649 TI - Two-dimensional resonant modes in stacked Josephson junctions. PMID- 9974651 TI - Tc suppression and conduction mechanisms in Bi2.1Sr1.93Ca0.97-xRxCu2O8+y (R=Pr, Gd, and Er) systems. PMID- 9974652 TI - Iterated perturbation theory for the attractive Holstein and Hubbard models. PMID- 9974653 TI - Effective action of a magnetic monopole in three-dimensional electrodynamics with massless matter and gauge theories of superconductivity. PMID- 9974655 TI - Monte Carlo method for a lattice superconductor with free surfaces. PMID- 9974654 TI - Dynamics of boson quantum films. PMID- 9974656 TI - Midinfrared conductivity in orientationally disordered doped fullerides. PMID- 9974657 TI - Temperature and electric-field dependence of hopping transport in low-dimensional devices. PMID- 9974658 TI - Phase diagram of flux creep in melt-textured and single-crystalline YBa2Cu3O7- delta. PMID- 9974659 TI - Critical current of a lateral Josephson junction for layered superconductors. PMID- 9974660 TI - Microstructure of directionally solidified high-critical-current YBa2Cu3O7 Y2BaCuO5 composites. PMID- 9974661 TI - Electronic phase separation: Extended mean-field calculations for CuO2 layers in high-Tc superconductors. PMID- 9974662 TI - Spin-phonon renormalization of the excitation energy in a dilute two-dimensional antiferromagnet. PMID- 9974663 TI - Electromagnetic phenomena related to a low-frequency plasma in cuprate superconductors. PMID- 9974664 TI - Tb oxidation state and hybridization in Y0.9Tb0.1Ba2Cu3O7- delta ( delta =0.02, 0.84): A magnetic-susceptibility and x-ray-absorption study. PMID- 9974665 TI - Long-time magnetic relaxation in a detwinned YBa2Cu3O7- delta single crystal. PMID- 9974666 TI - Systematic study of the growth-temperature dependence of structural disorder and superconductivity in YBa2Cu3O7- delta thin films. PMID- 9974667 TI - Spin susceptibility and gap structure of the fractional-statistics gas. PMID- 9974668 TI - Broad resistivity transitions in c-axis-in-plane-aligned a-axis-oriented YBa2Cu3Ox thin films. PMID- 9974670 TI - Small-angle multiple scattering in a dilute system with single refractive scattering on the inhomogeneities. PMID- 9974669 TI - Finite-temperature conductivity in the planar t-J model. PMID- 9974671 TI - Enhanced charge localization in the organic alloys PMID- 9974672 TI - One-dimensional chiral XY model for the Dhd phase of hexahexylthiotriphenylene. PMID- 9974673 TI - Neutron spectroscopic evidence of concentration-dependent hydrogen ordering in the octahedral sublattice of beta -TbH2+x. PMID- 9974674 TI - Phonon dispersion in Ni0.55Pd0.45 and Ni0.5Fe0.5 alloys. PMID- 9974675 TI - Generalized quantum Mattis spin glasses with p-spin interactions. PMID- 9974676 TI - Reassessment of the conduction-electron spin resonance of alkali metals in zeolites. PMID- 9974678 TI - Spin-triplet contribution to zero-field splittings for Fe2+ in GeFe2O4. PMID- 9974677 TI - X-ray-absorption study of the magnetic moments in thin Ni layers on Fe(100). PMID- 9974679 TI - Reentrant phase transition in the quantum-spin-glass model with the pseudoinverse rule. PMID- 9974680 TI - Antiferromagnetism in the Ho5Os4Ge10 system. PMID- 9974681 TI - Anomalous symmetry dependence of Rh13 magnetism. PMID- 9974682 TI - Superconducting phonon structure in the transition from tunneling to contact regime. PMID- 9974683 TI - Fluctuation phenomena in excess conductivity and magnetization of single-crystal Bi2Sr2CaCu2O8+y. PMID- 9974684 TI - Magnetic order of RBa2Cu4O8 (R=rare earth) due to dipole-dipole and exchange interactions. PMID- 9974685 TI - Collective creep of vortex bundles in YBa2Cu3O7 crystals. PMID- 9974686 TI - Density of normal carriers below Tc and thermal resistance of twin boundaries in YBa2Cu3O7-x single crystals. PMID- 9974687 TI - Orientational disorder and the band gap of solid molecular hydrogen under pressure. PMID- 9974688 TI - Glassy transition in the three-dimensional random-field Ising model. PMID- 9974689 TI - Eliashberg treatment of the microwave conductivity of niobium. PMID- 9974690 TI - Supercurrent determined from the Aharonov-Bohm effect in mesoscopic superconducting rings. PMID- 9974691 TI - Imaging of the dynamic magnetic structure in a parallel array of shunted Josephson junctions. PMID- 9974692 TI - Quasiparticle dispersion in the cuprate superconductors and the two-dimensional Hubbard model. PMID- 9974693 TI - In- and out-of-plane vortex correlations in YBa2Cu3O7. PMID- 9974694 TI - Freezing electronic correlations by polaronic instabilities in doped La2NiO4. PMID- 9974696 TI - Origin of dissipation in high-Tc superconductors. PMID- 9974695 TI - Effect of oxygen stoichiometry on the vortex-glass phase transition in YBa2Cu3O7- delta thin films. PMID- 9974697 TI - Sign reversals in the vortex-state Hall effect in Y-Ba-Cu-O: Correlations with the normal-state Seebeck coefficient. PMID- 9974698 TI - Calculations of the total energy, electron-phonon interaction, and Stoner parameter for metals. PMID- 9974699 TI - Symmetrized partial-wave method for density-functional cluster calculations. PMID- 9974700 TI - Numerical-scaling experiments in Anderson localization. PMID- 9974701 TI - Missing particles and modes. PMID- 9974702 TI - Applications of Engel and Vosko's generalized gradient approximation in solids. PMID- 9974703 TI - Temperature dependence of the Hartree-Fock approximation. PMID- 9974704 TI - Electronic properties of f-electron metals using the generalized gradient approximation. PMID- 9974705 TI - Equation-of-motion approach to the Hubbard model in infinite dimensions. PMID- 9974706 TI - Pseudogap formation in the symmetric Anderson lattice model. PMID- 9974707 TI - Local-field effects in NiO and Ni. PMID- 9974708 TI - Inelastic plasmon and interband electron-scattering potentials for Si from dielectric matrix calculations. PMID- 9974709 TI - Semiempirical tight-binding band structure of II3V2 semiconductors: Cd3P2, Zn3P2, Cd3As2, and Zn3As2. PMID- 9974710 TI - Photoluminescence of excitons bound to the isoelectronic hydrogen-related defects B711 (1.1377 eV) in silicon. PMID- 9974711 TI - Free energies, structures, and diffusion of point defects in Si using an empirical potential. PMID- 9974712 TI - Microvoid, Si, H, and Al dynamics in a-Si:H/Al2O3/Al structures: A small-angle x ray-scattering and infrared-absorption study. PMID- 9974713 TI - S-Cu-related metastable complex defect in Si by optical detection of magnetic resonance. PMID- 9974715 TI - Equilibrium temperature in intrinsic hydrogenated amorphous silicon under illumination. PMID- 9974714 TI - Influence of transition-metal type and content on local-order properties of Zn1 xMxS (M=Mn,Fe,Co) alloys studied using XANES spectroscopy. PMID- 9974716 TI - Conduction-band states and surface core excitons in InSb(110) and other III-V compounds. PMID- 9974717 TI - Pressure-induced symmetry breaking in tetrahedral networks. PMID- 9974718 TI - Ab initio study of hydrogenation effects in amorphous silicon carbide. PMID- 9974719 TI - Quantum theory of impact ionization in coherent high-field semiconductor transport. PMID- 9974721 TI - Steady-state optical modulation spectroscopy of p-type a-Si:H. PMID- 9974720 TI - Two-phonon resonant magneto-Raman scattering from direct-gap semiconductors. PMID- 9974722 TI - Ultrafast carrier-carrier scattering among photoexcited nonequilibrium carriers in GaAs. PMID- 9974723 TI - Identification of the migration path of interstitial carbon in silicon. PMID- 9974724 TI - Localization and diffusion of energy via confined phonon modes in semiconductor superlattices. PMID- 9974726 TI - Radiative recombination at the AlxGa1-xAs-GaAs heterostructure interface by two dimensional excitons. PMID- 9974725 TI - STM study of surface reconstructions of Si(111):B. PMID- 9974727 TI - Exciton mixing in the magnetophotoluminescence excitation spectra of shallow strained InxGa1-xAs/GaAs quantum wells. PMID- 9974728 TI - Selection rules of intersubband transitions in conduction-band quantum wells. PMID- 9974730 TI - Excitonic and other interband transitions in TlInS2 single crystals. PMID- 9974729 TI - Thermal vibration amplitudes and structure of As on Si(001). PMID- 9974732 TI - Reflectance study of the oscillator strength of excitons in semiconductor quantum wells. PMID- 9974731 TI - Strain and interdiffusion in semiconductor heterostructures. PMID- 9974733 TI - Raman line-shape analysis of random and spontaneously ordered GaInP2 alloy. PMID- 9974735 TI - Direct derivation of effective-mass equations for microstructures with atomically abrupt boundaries. PMID- 9974734 TI - Magnetic-field-induced localization effects on radiative recombination in GaAs/AlxGa1-xAs heterostructures. PMID- 9974736 TI - Integer quantum Hall transition: An alternative approach and exact results. PMID- 9974737 TI - Multiband theory of Bloch-electron dynamics in a homogeneous electric field. PMID- 9974738 TI - Surface phase transition and interface interaction in the alpha -Sn/InSb{111} system. PMID- 9974739 TI - Two-dimensional versus three-dimensional behavior of a free-carrier gas in delta doped p-type GaAs(001). PMID- 9974741 TI - General relation between carrier spatial distributions and the generation function in photoconductors. PMID- 9974740 TI - Green's-function approach to the electronic structure of double-barrier quantum well heterostructures. PMID- 9974742 TI - Interband magneto-optical studies of resonant polaron coupling in CdTe/Cd1-xMnxTe quantum wells. PMID- 9974743 TI - Local structures around Mn luminescent centers in Mn-doped nanocrystals of ZnS. PMID- 9974744 TI - Analysis of time behavior in the breakdown of the integral quantum Hall effect. PMID- 9974745 TI - Numerical analysis of electron-wave detection by a wedge-shaped point contact. PMID- 9974746 TI - Tunneling between a pair of parallel Hall droplets. PMID- 9974747 TI - Anomalous dynamic scaling on the ion-sputtered Si(111) surface. PMID- 9974748 TI - Electrophonon resonance in AlxGa1-xAs-GaAs quasi-two-dimensional quantum wells. PMID- 9974750 TI - Variations of the hole effective masses induced by tensile strain in In1 xGaxAs(P)/InGaAsP heterostructures. PMID- 9974749 TI - Persistent currents of interacting electrons in one-dimensional disordered rings. PMID- 9974751 TI - Coulomb interaction and persistent currents in ensembles of mesoscopic metal rings. PMID- 9974752 TI - Self-consistent electronic-structure calculation of rectangular modulation-doped GaAs/Ga1-xAlxAs quantum wires. PMID- 9974753 TI - Ultrafast Faraday spectroscopy in magnetic semiconductor quantum structures. PMID- 9974754 TI - Efficient calculation of the scattering rates in valence-band quantum wells. PMID- 9974755 TI - Transmission and reflection times of phonon packets propagating through superlattices. PMID- 9974756 TI - Magnetoexcitons in quantum wires with an anisotropic parabolic potential. PMID- 9974758 TI - Theory of asymmetric broadening and shift of excitons in quantum structures with rough interfaces. PMID- 9974757 TI - Sensitivity of wave-function envelopes upon interface position: Semiconductor insulator boundary. PMID- 9974759 TI - Degenerate Landau bands with interband disorder: A semiclassical picture. PMID- 9974760 TI - Fine structure of electron-transmission spectra across AlAs single barriers. PMID- 9974761 TI - Self-consistent calculations of edge channels in laterally confined two dimensional electron systems. PMID- 9974762 TI - Normal-incidence linear and nonlinear infrared optical response of L-valley quantum-well structures. PMID- 9974763 TI - Universal spectral correlations in diffusive quantum systems. PMID- 9974764 TI - Electric-field-induced second-harmonic generation mediated by one-dimensional excitons in polysilanes. PMID- 9974765 TI - Propagation and attenuation of pseudo surface acoustic modes at the (111) face of a GaAs crystal studied by Brillouin spectroscopy. PMID- 9974766 TI - Electronic structure and magnetism of the semimetals ErAs and ErxSc1-xAs. PMID- 9974767 TI - Polariton effects in four-wave mixing. PMID- 9974768 TI - Second-order nonlinear optical susceptibility of asymmetric quantum wells. PMID- 9974769 TI - Transfer-energy-dependent escape rate of electrons through a small-capacitance tunnel junction. PMID- 9974771 TI - Structural properties of granular PdxC1-x films. PMID- 9974770 TI - Strain dependence of the valence-band offset in InAs/GaAs heterojunctions determined by ultraviolet photoelectron spectroscopy. PMID- 9974772 TI - Photoemission from adsorbate-covered Ag films: The dispersion relation for Ag plasma excitation. PMID- 9974774 TI - O- ions in front of a metal surface: Application to an O(1D,1S) quenching process. PMID- 9974773 TI - Structure of Ni(100)-c(2 x 2)-Na: A LEED analysis. PMID- 9974776 TI - Comparison of theoretical methods for the calculation of extended x-ray absorption fine structure. PMID- 9974775 TI - Spectroscopic signature of Cu on W(110) from scanning tunneling microscopy and inverse photoemission. PMID- 9974777 TI - Evidence for rhombohedral boron nitride in cubic boron nitride films grown by ion assisted deposition. PMID- 9974778 TI - Voltage-activated charge motion measured by a mesoscopic two-tunnel-junction system. PMID- 9974779 TI - Moving gold atoms with an atomic-force-microscope tip: A study of dimer and trimer formation on NaCl(100). PMID- 9974780 TI - Relativistic electronic structure of random alloys and their surfaces by linear band-structure methods. PMID- 9974781 TI - Structural, electronic, and magnetic properties of small rhodium clusters. PMID- 9974782 TI - Adsorption on a stepped substrate. PMID- 9974783 TI - First-principles calculations of the surface relaxation and electronic structure of Zr(0001). PMID- 9974785 TI - Model for the shapes of islands and pits on (111) surfaces of fcc metals. PMID- 9974784 TI - Atomic-scale structure and electronic properties of highly tetrahedral hydrogenated amorphous carbon. PMID- 9974786 TI - Analytical solution of generalized Burton-Cabrera-Frank equations for growth and post-growth equilibration on vicinal surfaces. PMID- 9974787 TI - Nonrelativistic multiple-scattering theory of a spin-polarized electron. PMID- 9974788 TI - Probing the electronic structure in M2Mo6Se6: Quadrupole couplings measured by NMR. PMID- 9974790 TI - Valence-band spectra of alpha -TeO2. PMID- 9974789 TI - Dimensionality crossovers of the sigma plasmon in coaxial carbon nanotubes. PMID- 9974791 TI - Effective-medium theory for two-component nonlinear composites. PMID- 9974792 TI - Hot-electron cooling and hot-phonon generation with collision broadening. PMID- 9974793 TI - Real-space Green's-function approach to study the effects of disorder on the frequency spectrum of Si/Ge alloys. PMID- 9974794 TI - Two-electron state and negative-U property of sulfur DX centers in GaAs1-xPx. PMID- 9974797 TI - Theoretical model of excitons for type-II quantum-wire systems. PMID- 9974795 TI - Exciton oscillator strength in quantum wells: From localized to free resonant states. PMID- 9974796 TI - Structural analysis of the (1 x 1)-Bi/GaAs(110) interface. PMID- 9974798 TI - Determination of the fundamental and split-off band gaps in zinc-blende CdSe by photomodulation spectroscopy. PMID- 9974800 TI - Ordering of amorphous silicon during solid-phase epitaxy studied by scanning tunneling microscopy. PMID- 9974799 TI - Time-resolved electron-temperature measurement in a highly excited gold target using femtosecond thermionic emission. PMID- 9974802 TI - Decomposition approach to a two-dimensional electron system with an even denominator filling factor. PMID- 9974801 TI - Resonant resistance enhancement in double-quantum-well GaAs-AlxGa1-xAs heterostructures. PMID- 9974804 TI - Resonant tunneling through quantum-dot arrays. PMID- 9974803 TI - Multipole edge plasmons of two-dimensional electron-gas systems. PMID- 9974805 TI - Possible metal-insulator transition at B=0 in two dimensions. PMID- 9974807 TI - X-ray-absorption dichroism of Dy at interfaces. PMID- 9974806 TI - Modification of spatiotemporal pattern formation in an excitable medium by continuous variation of its intrinsic parameters: CO oxidation on Pt(110). PMID- 9974808 TI - Light-intensity dependence of the photoconductivity in C60 films. PMID- 9974809 TI - Valence-electron distribution of cesium crown-ether electrides. PMID- 9974810 TI - Electride-electron locations in the crystalline electride PMID- 9974812 TI - Atomic geometry and electronic structure of native defects in GaN. PMID- 9974811 TI - Role of quantum fluctuations in the temperature dependence of intragap absorption in an MX chain complex. PMID- 9974813 TI - Interdiffusion of the group-III sublattice in In-Ga-As-P/In-Ga-As-P and In-Ga As/In-Ga-As heterostructures. PMID- 9974815 TI - Instantons and the spectral function of electrons in the half-filled Landau level. PMID- 9974816 TI - Ballistic-electron-emission microscopy of strained Si1-xGex layers. PMID- 9974814 TI - Resonant tunneling through donor molecules. PMID- 9974817 TI - Visible photoluminescence from N-dot ensembles and the linewidth of ultrasmall AlyIn1-yAs/AlxGa1-xAs quantum dots. PMID- 9974819 TI - Type-II-->type-I transition in (GaX)n/(InX)n (001) superlattices (X=P, Sb) as a function of period n. PMID- 9974818 TI - Experimental characterization of electron trajectories in antidot lattices. PMID- 9974820 TI - Arsenic-deficient GaAs(001)-(2 x 4) surfaces: Scanning-tunneling-microscopy evidence for locally disordered (1 x 2) Ga regions. PMID- 9974821 TI - Si 2p core-level chemical shifts at the H/Si(111)-(1 x 1) surface. PMID- 9974822 TI - Electro-optic detection of Bloch oscillations. PMID- 9974823 TI - Biexciton effects in femtosecond nonlinear transmission of semiconductor quantum dots. PMID- 9974824 TI - Simultaneous influence of disorder and Coulomb interaction on photon echoes in semiconductors. PMID- 9974825 TI - Supercurrent transport through a high-mobility two-dimensional electron gas. PMID- 9974826 TI - Origin of RHEED intensity oscillations during the growth of (Y,Dy)Ba2Cu3O7-x thin films. PMID- 9974827 TI - Structural analyses of ordered rubidium phases on Ru(0001) using low-energy electron diffraction. PMID- 9974828 TI - Magnetic linear dichroism and spin polarization in 3d-band photoemission. PMID- 9974829 TI - Constraints on small graphitic helices. PMID- 9974831 TI - X-ray-scattering measurements of the transient structure of a driven charge density wave. PMID- 9974830 TI - Erratum: Absorption and luminescence studies of free-standing porous silicon films PMID- 9974832 TI - Electronic structure and magnetism of KMF3 (M=Mn,Fe,Co,Ni). PMID- 9974834 TI - Conserving approximations: Electron gas with exchange effects. PMID- 9974833 TI - Dynamical local-field factors and effective interactions in the three-dimensional electron liquid. PMID- 9974836 TI - Electrical resistivities of gamma -phase FexNi80-xCr20 alloys. PMID- 9974835 TI - Electrical conductivity of lithium-intercalated thiophosphate NiPS3 single crystals. PMID- 9974837 TI - Magnetic, transport, and structural properties of Fe1-xIrxSi. PMID- 9974839 TI - Phenomenological Ginzburg-Landau theory of charge-density-wave spectra. PMID- 9974838 TI - Density-functional calculation of the electronic structure and equilibrium geometry of iron pyrite (FeS2). PMID- 9974840 TI - Inequivalence of weak localization and coherent backscattering. PMID- 9974842 TI - Luttinger liquid in a solvable two-dimensional model. PMID- 9974841 TI - Manifestation of quantum chaos in electronic band structures. PMID- 9974844 TI - Use of the Lloyd formula for binary alloys. PMID- 9974843 TI - First-principles calculation of NiO valence spectra in the impurity-Anderson model approximation. PMID- 9974845 TI - Cooperons at the metal-insulator transition revisited: Constraints on the renormalization group and a conjecture. PMID- 9974847 TI - Phonon scattering from residual defects in GaAs: Observation of optically induced metastability by phonon imaging. PMID- 9974846 TI - Charge-density-wave structure in NbSe3. PMID- 9974848 TI - Dynamics of the nitrogen-bound excitons in 6H SiC. PMID- 9974849 TI - Time-convolutionless reduced-density-operator theory of an arbitrary driven system coupled to a stochastic reservoir: Quantum kinetic equations for semiconductors. PMID- 9974850 TI - Iron and chromium impurities in ZnSe as centers of nonradiative recombination. PMID- 9974852 TI - Ab initio molecular-dynamics study of structural, dynamical, and electronic properties of liquid Ge. PMID- 9974851 TI - Hydrodynamic fluctuations of a hot-electron gas. PMID- 9974853 TI - Picosecond energy relaxation rates of hot excitonic molecules in CdSe. PMID- 9974854 TI - Normal-state tunnel junction as a tunable quasimonochromatic phonon source. PMID- 9974855 TI - Theory of Zener tunneling and Wannier-Stark states in semiconductors. PMID- 9974856 TI - Ab initio calculations of anharmonicity of the C-H stretch mode in HCN and GaAs. PMID- 9974858 TI - Nucleation and initial growth phase of diamond thin films on (100) silicon. PMID- 9974857 TI - Tetrahedral structures and phase transitions in III-V semiconductors. PMID- 9974859 TI - Microscopic calculation of second-harmonic generation at semiconductor surfaces: As/Si(111) as a test case. PMID- 9974860 TI - Phonon-assisted tunneling from a two-dimensional emitter state. PMID- 9974861 TI - Temperature-dependent optical band gap of the metastable zinc-blende structure beta -GaN. PMID- 9974862 TI - Ultrafast phase dynamics of coherent emission from excitons in GaAs quantum wells. PMID- 9974864 TI - Electron-electron interaction and the persistent current in a quantum ring. PMID- 9974863 TI - C60-induced reconstruction of the Ge(111) surface. PMID- 9974865 TI - Scattering-matrix method for ballistic electron transport: Theory and an application to quantum antidot arrays. PMID- 9974866 TI - Initial stages of InAs epitaxy on vicinal GaAs(001)-(2 x 4). PMID- 9974867 TI - Quenching mechanisms of nonlocal transport in laterally confined two-dimensional systems. PMID- 9974868 TI - Hole subband states of GaAs/AlxGa1-xAs quantum wells within the 6 x 6 Luttinger model. PMID- 9974869 TI - Theoretical study of grain boundaries in Si: Effects of structural disorder on the local electronic structure and the origin of band tails. PMID- 9974870 TI - Spin-split subbands and magneto-oscillations in III-V asymmetric heterostructures. PMID- 9974872 TI - Carrier-gain dynamics in InxGa1-xAs/AlyGa1-yAs strained-layer single-quantum-well diode lasers: Comparison of theory and experiment. PMID- 9974871 TI - Atomic arrangements of 16 x 2 and (17,15,1) 2 x 1 structures on a Si(110) surface. PMID- 9974873 TI - Current fluctuations in strongly electron-correlated one-dimensional double barrier heterostructures. PMID- 9974874 TI - Limitations to the realization of noncentrosymmetric SimGen superlattices. PMID- 9974875 TI - Local-field effect on the linear optical intersubband absorption in multiple quantum wells. PMID- 9974876 TI - Influence of quantum-interference effects on hole mobility in superlattices. PMID- 9974877 TI - Fano effect of resonant Raman scattering in a semiconductor quantum well. PMID- 9974878 TI - Effects of spin-orbit interaction on the envelope-function equations for semiconductor heterostructures. PMID- 9974879 TI - Effective-mass theory for GaAs/Ga1-xAlxAs quantum wires and corrugated superlattices grown on (311)-oriented substrates. PMID- 9974880 TI - Hydrogen adsorption on GaAs(110): A study of the surface optical properties. PMID- 9974881 TI - Atomic and electronic structure of the GaAs/ZnSe(001) interface. PMID- 9974882 TI - Hysteresis and defects of spin-polarized edge states in the integer quantum Hall regime. PMID- 9974883 TI - Magnetotransport in a two-dimensional tight-binding model. PMID- 9974884 TI - Dynamics of electric-field domains and oscillations of the photocurrent in a simple superlattice model. PMID- 9974885 TI - Tight-binding model for the transverse Shubnikov-de Haas effect in semiconductor superlattices. PMID- 9974887 TI - Electronic structures of As/Si(001) 2 x 1 and Sb/Si(001) 2 x 1 surfaces. PMID- 9974886 TI - Nonparabolicity and a sum rule associated with bound-to-bound and bound-to continuum intersubband transitions in quantum wells. PMID- 9974888 TI - Schottky-barrier height and electronic structure of the Si interface with metal silicides: CoSi2, NiSi2, and YSi2. PMID- 9974889 TI - Electronic structure of n-type delta -doping multiple layers and superlattices in silicon. PMID- 9974890 TI - Current-voltage characteristic in narrow channels and low-voltage breakdown of the quantum Hall effect. PMID- 9974892 TI - Electric-field-induced Gamma -X mixing between Stark ladders in short-period GaAs/AlAs superlattices. PMID- 9974891 TI - Dielectric function and collective modes of two-dimensional interacting bosons. PMID- 9974893 TI - Drastic suppression of scattering and activated behavior in mesoscopic quantum Hall systems with smooth confinement. PMID- 9974894 TI - Quantum fluctuations of the charge near the Coulomb-blockade threshold. PMID- 9974896 TI - Nonadiabatic processes during the oxidation of Li layers. PMID- 9974895 TI - Optical anisotropy in InAs/AlSb superlattices. PMID- 9974897 TI - Dislocation-mediated healing of ideal and adsorbed monolayers with vacancy damage. PMID- 9974898 TI - Observation of valence-band structure in the LVV Auger spectra of thin epitaxial sodium layers. PMID- 9974899 TI - Dynamic scaling of the island-size distribution and percolation in a model of submonolayer molecular-beam epitaxy. PMID- 9974900 TI - Scanning-tunneling-microscopy studies of the S-induced reconstruction of Cu(100). PMID- 9974901 TI - Reconstructive interactions in mixed N+O layers on Rh(110). PMID- 9974902 TI - Charge-density-wave transformation induced by Na intercalation into 1T-TaS2. PMID- 9974903 TI - Spin-polarized electrons at interfaces: Co/Cu systems. PMID- 9974904 TI - Optical absorption of C60: Singlet single-excitation calculations. PMID- 9974905 TI - One-dimensional quantum liquid comprised of particles with an arbitrary number of internal degrees of freedom. PMID- 9974906 TI - Variational theory for a finite-U periodic Anderson model: Application to heavy electron materials. PMID- 9974907 TI - Calculation of atomic forces using the linearized-augmented-plane-wave method. PMID- 9974908 TI - Solid solubilities of magnetic ions in diluted magnetic semiconductors grown under equilibrium conditions. PMID- 9974909 TI - Electron transport through antidot superlattices in Si/Si0.7Ge0.3 heterostructures. PMID- 9974911 TI - Inelastic events do not just randomize the phase. PMID- 9974910 TI - Coherent electronic backscattering in ballistic microstructures. PMID- 9974912 TI - Thermalization of a one-dimensional electron gas by many-body Coulomb scattering: Molecular-dynamics model for quantum wires. PMID- 9974914 TI - Determination of the Compton wavelength on a superlattice. PMID- 9974913 TI - Resonant tunneling in two dimensions via an impurity. PMID- 9974915 TI - Calculated defect states in semiconductor superlattices within a tight-binding model. PMID- 9974916 TI - Possiblity of terahertz emission with a time-dependent amplitude in semiconductor quantum wells. PMID- 9974918 TI - Quantum and many-body effects on the capacitance of a spherical-shell quantum dot. PMID- 9974917 TI - Implications of the two-band model for quantum wells. PMID- 9974919 TI - Zeeman splitting of the excitonic recombination in InxGa1-xAs/GaAs single quantum wells. PMID- 9974920 TI - Pressure coefficient of the PbTe metastable CsCl-type-phase energy gap. PMID- 9974921 TI - Surface-phonon dispersion curves and the longitudinal resonance in Ag(001) observed by helium-atom scattering. PMID- 9974922 TI - Fractal properties of a one-dimensional film surface. PMID- 9974924 TI - Comment on "Growth and characterization of epitaxial cubic boron nitride films on silicon" PMID- 9974923 TI - Tight-binding molecular-dynamics study of transition-metal clusters. PMID- 9974925 TI - Role of covalent bonding in the polarization of perovskite oxides: The case of KNbO3. PMID- 9974926 TI - High-resolution temperature-dependent photoemission spectroscopy of FeSi: Evidence for localized states. PMID- 9974927 TI - Identification of neutral bond-centered muonium in n-type semiconductors by longitudinal muon-spin relaxation. PMID- 9974928 TI - Intersubband L-valley and heavy-hole transitions in undoped GaSb/AlSb superlattices. PMID- 9974929 TI - Shifts and widths of metal-overlayer quantum-well states near EF observed by photoemission. PMID- 9974931 TI - Dynamic image potential in mesoscopic systems. PMID- 9974930 TI - Radiative lifetimes of excitons in quantum wires. PMID- 9974932 TI - Giant magnetoresistance in lateral surface superlattices. PMID- 9974933 TI - Reaction pathway for Sb-dimer rotation in conversion of Sb4 precursors on Si(001). PMID- 9974934 TI - Observation of solid-hexatic-liquid phase transitions of submonolayer xenon on graphite by transmission-electron diffraction. PMID- 9974935 TI - Sulfur chemisorption on Ni(111): The clock structure of the (5 sqrt 3 x 2)S phase. PMID- 9974936 TI - Hybridization and the effective mass of quantum-well states in magnetic multilayers. PMID- 9974937 TI - Time-resolved two-photon photoemission from Cu(100): Energy dependence of electron relaxation. PMID- 9974938 TI - Single-electron tunneling effects in granular metal films. PMID- 9974939 TI - Thermodynamics of superconducting UPt3 under uniaxial pressure. PMID- 9974940 TI - Structural and elastic properties of Ge after Kr-ion irradiation at room temperature. PMID- 9974941 TI - Femtosecond time-resolved spectroscopy of soft modes in structural phase transitions of perovskites. PMID- 9974942 TI - Kinetics of the martensitic transition in In-Tl alloys. PMID- 9974944 TI - Temperature dependence of the homogeneous width of Eu3+ spectral lines in silicate glass measured by accumulated photon echoes. PMID- 9974943 TI - Corrections of residual fluorescence distortions for a glancing-emergence-angle x ray-absorption technique. PMID- 9974945 TI - Electron correlation in CaF2 studied in threshold-excited soft-x-ray fluorescence. PMID- 9974946 TI - Entropy change between the beta phase and the martensite in Cu-based shape-memory alloys. PMID- 9974947 TI - Geometrical microstructure of FeNb3+-VO defects in KNbO3. PMID- 9974948 TI - Structural and bonding properties of solid tellurium from first-principles calculations. PMID- 9974950 TI - K+LMM resonant Auger spectra of solid KF. PMID- 9974949 TI - Mechanical instabilities in AlPO4. PMID- 9974952 TI - Spatial phase modulation due to the thermal nonlinearity in semiconductor-doped glasses. PMID- 9974951 TI - Computer simulations of 1q and 2q modulated phases in the tetragonal model. PMID- 9974953 TI - Structure of sputtered and melt-spun Ni-Zr glassy metals. PMID- 9974955 TI - Oscillatory instabilities in directionally solidified eutectics. PMID- 9974954 TI - Excitation oscillations in conformationally disordered chains with random traps. PMID- 9974957 TI - Nucleation in disordered media. PMID- 9974956 TI - Tight-binding models for hot dense hydrogen. PMID- 9974958 TI - Origin of depolarization dispersion of totally symmetric fundamental transitions in the resonance Raman effect of soluble cis-polyacetylene. PMID- 9974960 TI - Theory of diffusion in a porous medium with applications to pulsed-field-gradient NMR. PMID- 9974959 TI - Anharmonic gap mode in a one-dimensional diatomic lattice with nearest-neighbor Born-Mayer-Coulomb potentials and its interaction with a mass-defect impurity. PMID- 9974961 TI - Optical phonons, crystal-field transitions, and europium luminescence-excitation processes in Eu2BaCoO5: Experiment and theory. PMID- 9974963 TI - Inelastic-neutron-scattering study of the spin dynamics in the Haldane-gap system Ni(C2H8N2)2NO2ClO4. PMID- 9974964 TI - Structural and magnetic properties of CuCl2 graphite intercalation compounds. PMID- 9974962 TI - Variational cumulant expansion for the Heisenberg model with the critical temperature determined to third order. PMID- 9974965 TI - Magnetic short-range order and magnetic moments of Co-Mn and Ni-Mn alloys. PMID- 9974966 TI - Effect of a magnetic field on a vibrating reed with anisotropic susceptibility. PMID- 9974969 TI - Propagation of a hole on a Neel background. PMID- 9974967 TI - First-principle study of hybridization effects and magnetic ordering in correlated-electron uranium systems. PMID- 9974968 TI - Field-induced magnetism in uranium compounds: UGe3 and URh3. PMID- 9974970 TI - Equation of motion for two coupled spin-1 nuclei under a coherent and random Hamiltonian. PMID- 9974971 TI - Magnetism of UT2Si2 (T=Cr,Mn,Fe,Co,Ni,Cu,Ru,Rh,Pd,Os) from spin-density functional calculations. PMID- 9974972 TI - sigma -model study of Haldane-gap antiferromagnets. PMID- 9974973 TI - Ordering process and Bloch-wall dynamics in a nearly one-dimensional anisotropic spin system. PMID- 9974974 TI - Finite-size analysis of the structure factors in the one-dimensional spin-1/2 antiferromagnetic XXZ model. PMID- 9974975 TI - Polarized-neutron-diffraction study of the magnetization density in hexagonal Y2Fe17. PMID- 9974977 TI - Detailed magnetization study of quenched random ferromagnets. I. Low-lying magnetic excitations. PMID- 9974976 TI - Pressure- and field-dependent behavior of YbCu4Au. PMID- 9974978 TI - Detailed magnetization study of quenched random ferromagnets. II. Site dilution and percolation exponents. PMID- 9974979 TI - Critical exponents at the ferromagnetic phase transition of Fe100-xPtx single crystals. PMID- 9974980 TI - Nonlocal distribution of the recombination energy in spin-polarized atomic hydrogen. PMID- 9974982 TI - Dynamics of an ac-driven string of fluxons in a multilayered Josephson junction. PMID- 9974981 TI - Superconducting fluctuation effects on the thermoelectric coefficient above the transition temperature. PMID- 9974984 TI - Cross-talk effects in superconductor-insulator-normal-metal trilayers. PMID- 9974983 TI - Hysteretic ac losses and susceptibility of thin superconducting disks. PMID- 9974985 TI - Nonadiabatic analysis of the Josephson critical current influenced by quantum phase fluctuations. PMID- 9974986 TI - Spatiotemporal chaos in Josephson-junction arrays. PMID- 9974987 TI - Dynamics of row-switched states in Josephson-junction arrays. PMID- 9974988 TI - Influence of induced magnetic fields on Shapiro steps in Josephson-junction arrays. PMID- 9974989 TI - In-plane thermoelectric power of c-axis-oriented Sr1-xNdxCuO2- delta thin films. PMID- 9974990 TI - Decrease in critical temperature due to disorder and magnetic correlations in two dimensional superconductors. PMID- 9974991 TI - Evidence for parallel junctions within high-Tc grain-boundary junctions. PMID- 9974992 TI - Observation of Hendricks-Teller partial order in a tetragonal cuprate superconductor: La1.68Nd0.14Na0.10K0.082CuO4. PMID- 9974993 TI - Nonadiabatic and nonlocal electron-phonon interaction and phonon-plasmon mixing in the high-temperature superconductors. PMID- 9974995 TI - Low-temperature quantum relaxation of single two-dimensional vortices in an epitaxial Tl2Ba2Ca2Cu3Ox thin film. PMID- 9974994 TI - Hall coefficient for oxygen-reduced Nd2-xCexCuO4- delta. PMID- 9974996 TI - Superconductivity in (LuC)2(Ni2B2) and (LuC)(Ni2B2). PMID- 9974997 TI - Phonon self-energy in a d-wave superconductor with retardation, finite temperature, and impurities. PMID- 9974998 TI - Scaling in high-temperature superconductors. PMID- 9974999 TI - Reversible magnetization of radiation-disordered YBa2Cu3O7-x single crystals. PMID- 9975000 TI - Charge excitation and the normal-state transport properties in the flux-binding phase of the t-J model. PMID- 9975001 TI - Flux creep through columnar defects. PMID- 9975002 TI - Disorder-induced transition of the vortex lattice in YBa2Cu3O7 crystals and films. PMID- 9975003 TI - Observation of in-plane anisotropy of vortex pinning by inclined columnar defects. PMID- 9975004 TI - Crystal structure of Sr0.875Nd0.125CuO2- delta superconducting thin films. PMID- 9975006 TI - Doping dependence of the electronic structure and magnetic order in high-Tc superconductors. PMID- 9975005 TI - Phonons and superconductivity in YBa2Cu3O7. PMID- 9975007 TI - Order and disorder in the ensemble of Cu-O chain fragments in oxygen-deficient planes of YBa2Cu3O6+x. PMID- 9975008 TI - Critical-state-model parameters of polycrystalline YBa2Cu3O7: Critical current in thin slabs and field penetration in hollow cylinders. PMID- 9975009 TI - Relation of extended Van Hove singularities to high-temperature superconductivity within strong-coupling theory. PMID- 9975011 TI - Topology of forward scattering of neutrons from imperfect multilayers. PMID- 9975010 TI - UV-spectroscopy study of the Ce7Rh3 empty and filled valence states. PMID- 9975012 TI - Far-infrared study of low-frequency vibrational states in As2S3 glass. PMID- 9975013 TI - Spontaneous optical flashes in proton-irradiated solid deuterium. PMID- 9975014 TI - Ferromagnetic transition of the Kondo lattice with Coulomb repulsion: Exact results. PMID- 9975015 TI - dc and ac resistivity of amorphous UCu4+xAl8-x thin films. PMID- 9975016 TI - Magnetic ordering of Mn overlayers on GaAs(100). PMID- 9975018 TI - Kosterlitz-Thouless transition in a two-dimensional isotropic antiferromagnet in a uniform field. PMID- 9975017 TI - Spin-disordered states in the antiferromagnetic Heisenberg model on the triangular lattice. PMID- 9975019 TI - Crystallography and magnetism of the heavy-fermion compound YbBiPt. PMID- 9975020 TI - Dichroic interference effects in circularly polarized soft-x-ray resonant magnetic scattering. PMID- 9975022 TI - Thermodynamics and excitation spectrum of a quasi-one-dimensional superconductor in a high magnetic field. PMID- 9975021 TI - Magnetism-induced ordering in two and three dimensions. PMID- 9975023 TI - Negative four-probe conductances of mesoscopic superconducting wires. PMID- 9975024 TI - Effect of uniaxial pressure on the superconducting transition in YBa2Cu3O7. PMID- 9975025 TI - Calorimetric studies on the magnetic order of Pb2Sr2TbCu3O8+ delta. PMID- 9975026 TI - Effective electron-electron interaction in the two-dimensional Hubbard model. PMID- 9975027 TI - Anisotropy of superconducting Pb2Sr2(Y0.7Ca0.3)Cu3O8+ delta and Pb2Sr2Y1-yCu3O8+ delta. PMID- 9975028 TI - Thermoelectric power above the Kosterlitz-Thouless transition. PMID- 9975029 TI - Comment on "Time-differential perturbed-angular-correlation studies of the amorphous Cu-Hf alloys prepared by mechanical alloying and melt spinning" PMID- 9975030 TI - Reply to "Comment on 'Time-differential perturbed-angular-correlation studies of the amorphous Cu-Hf alloys prepared by mechanical alloying and melt spinning' " PMID- 9975031 TI - Delayed electron emission from electronically sputtered C60- ions. PMID- 9975032 TI - Semiconductorlike transport in highly ordered Al-Cu-Ru quasicrystals. PMID- 9975033 TI - Localization of light in coherently amplifying random media. PMID- 9975034 TI - Structural and dynamical properties of metastable Al:Si solid solutions calculated by the embedded-atom method. PMID- 9975035 TI - Possible soliton motion in ac-driven damped nonlinear lattices. PMID- 9975037 TI - Photoemission and inverse-photoemission study of superconducting YNi2B2C: Effects of electron-electron and electron-phonon interactions. PMID- 9975036 TI - Imaging short-range magnetic order by spin-polarized photoelectron holography. PMID- 9975038 TI - Observation of Josephson self-coupling in Nb/AlOx/Nb tunnel junctions. PMID- 9975039 TI - Magnetic pair breaking in HoNi2B2C. PMID- 9975040 TI - Anomalous behavior of the complex conductivity of Y1-xPrxBa2Cu3O7 observed with THz spectroscopy. PMID- 9975041 TI - Exact solution of a one-dimensional fermion model with interchain tunneling. PMID- 9975042 TI - Linear ac magnetic response near the vortex-glass transition in single crystalline YBa2Cu3O7. PMID- 9975043 TI - Flux cutting in YBa2Cu3O7- delta single crystals: Experiment and phenomenological model. PMID- 9975044 TI - Absence of a second antiferromagnetic transition in pure YBa2Cu3O6+x. PMID- 9975045 TI - Erratum: Transition-metal granular solids: Microstructure, magnetic properties, and giant magnetoresistance PMID- 9975046 TI - Spectroscopic study and crystal-field analysis of Cm3+ in the cubic-symmetry site of ThO2. PMID- 9975047 TI - Photoconductivity in KTaO3:Li single crystals. PMID- 9975048 TI - Thermal fluctuations and NMR spectra of incommensurate insulators. PMID- 9975049 TI - 57Fe-ion implantation in laser-deposited cupric and cuprous oxide films: Mossbauer spectroscopy and x-ray-diffraction studies. PMID- 9975050 TI - Extended x-ray-absorption fine-structure and perturbed-angular-correlation study of impurity clustering in dilute nickel alloys. PMID- 9975051 TI - Absorption-line-shape model for F-center-CN--molecule defect pairs in CsCl. PMID- 9975052 TI - Projectile and target autoionization electron emission in 700-eV Ne+-Na/M (M=Cr, Cu, Mo, and Pt) collisions. PMID- 9975053 TI - Nonmonotonic dependence of the positron lifetimes on the dopant content in La doped BaTiO3. PMID- 9975055 TI - Radiation damage in NaCl. I. Optical-absorption experiments on heavily irradiated samples. PMID- 9975054 TI - Renormalization-group calculation of Tc-T* of the nematic-isotropic phase transition. PMID- 9975056 TI - Radiation damage in NaCl. II. The early stage of F-center aggregation. PMID- 9975058 TI - Radiation damage in NaCl. IV. Raman scattering. PMID- 9975057 TI - Radiation damage in NaCl. III. Melting phenomena of sodium colloids. PMID- 9975059 TI - Radiation-enhanced diffusion in amorphous Ni-Zr studied by in situ electron irradiation in a transmission electron microscope. PMID- 9975060 TI - Experimental verification of light localization for disordered multilayers in the visible-infrared spectrum. PMID- 9975061 TI - Confinement potential and pi -electron delocalization in polyconjugated organic materials. PMID- 9975062 TI - Equilibrium properties of a quadrupolar glass. PMID- 9975063 TI - Effects of frustration and localization of states in the Penrose lattice. PMID- 9975064 TI - Electronic structure and transport in a model approximant of the decagonal quasicrystal Al-Cu-Co. PMID- 9975066 TI - Soliton dynamics and interaction in a deterministic aperiodic nonlinear lattice. PMID- 9975065 TI - Localized modes in inhomogeneous one-dimensional anharmonic lattices. PMID- 9975067 TI - Tracer diffusion in lattices with double occupancy of sites. PMID- 9975068 TI - Mossbauer study of SnO lattice dynamics. PMID- 9975069 TI - Paramagnetic scattering from the valence-fluctuation compound YbAl3. PMID- 9975070 TI - Intrinsic and induced Mn moments in Dy1-xYxMn2. PMID- 9975072 TI - Competition between singlet formation and magnetic ordering in one-dimensional spin systems. PMID- 9975071 TI - Magnetostatic modes in semi-infinite magnetic-nonmagnetic superlattices for an arbitrary-angle magnetization geometry. PMID- 9975074 TI - Thermoremanent-magnetization relaxation in the insulating spin glass Co1-xMnxCl2 PMID- 9975073 TI - Magnetic phase diagram of Y2CuO4: Weak ferromagnetism and metamagnetic transition. PMID- 9975075 TI - Model calculation for the susceptibility of a quantum spin glass. PMID- 9975076 TI - Effects of hydrogen doping on UPd2Al3. PMID- 9975077 TI - Aspects of strongly correlated insulators. PMID- 9975079 TI - Infinite-range-interaction M-component quantum spin glasses: Statics and dynamics in the large-M limit. PMID- 9975078 TI - Relation between interface roughness and giant magnetoresistance in MBE-grown polycrystalline Fe/Cr superlattices. PMID- 9975080 TI - Transfer-matrix scaling from disorder-averaged correlation lengths for diluted Ising systems. PMID- 9975081 TI - Interpretation of the giant magnetoresistance effect in Co/Cu(100) multilayers with the quantum model of giant magnetoresistance. PMID- 9975082 TI - Magnetic anisotropy of a free-standing Co monolayer and of multilayers which contain Co monolayers. PMID- 9975084 TI - Critical behavior near a symmetry-breaking surface and the stress tensor. PMID- 9975083 TI - Structural, electronic, and magnetic properties of Fe16N2. PMID- 9975085 TI - Micromagnetic theory of spin waves in rare-earth-transition-metal compounds. PMID- 9975086 TI - Generalization of the Abragam relaxation function to a longitudinal field. PMID- 9975087 TI - Spin bags in the doped t-J model. PMID- 9975088 TI - Exact spectra, spin susceptibilities, and order parameter of the quantum Heisenberg antiferromagnet on the triangular lattice. PMID- 9975089 TI - Quantum corrections to the resistance of Mo/Si multilayers. PMID- 9975090 TI - Numerical investigation of the flow properties of He II. PMID- 9975092 TI - Quantum Hall effect in ideal superconducting arrays at zero temperature. PMID- 9975091 TI - Granular behavior in polycrystalline Sm2-xCexCuO4-y compounds. PMID- 9975094 TI - Magnetization of symmetric 0- pi Josephson junctions. PMID- 9975093 TI - Quantum Hall fluid of vortices in a two-dimensional array of Josephson junctions. PMID- 9975095 TI - Proximity effect of thin films on superconducting substrates. PMID- 9975097 TI - Transfer-integral expansion for the d-p model of the CuO2 plane: A single hole in the antiferromagnetic state. PMID- 9975096 TI - Electron-correlation effects on the properties of LaxSr1-xTiO3. PMID- 9975099 TI - Self-consistent calculations of superconductivity in a nearly antiferromagnetic Fermi liquid. PMID- 9975098 TI - Impurity effects on the spin excitation spectrum in anisotropic superconductors. PMID- 9975100 TI - Mossbauer, crystal-structure, magnetic, and Raman studies of the (Y,Ce)2Sr2CuFeO8 compound isomorphic to superconductors with the T* structure. PMID- 9975101 TI - Response function of the t-J model calculated using anyon techniques. PMID- 9975102 TI - Bosonization of lattice fermions. PMID- 9975103 TI - Intergranular and intragranular critical currents in silver-sheathed Pb-Bi-Sr-Ca Cu-O tapes. PMID- 9975105 TI - Bihybridization model of Y1-xPrxBa2Cu3O7-y. PMID- 9975104 TI - Anomalous band folding due to the BiO superstructure in Bi2Sr2CaCu2O8 studied by angle-resolved photoemission. PMID- 9975106 TI - Superconductivity and valence state of Tl in TlA2-xLaxCuO5 and TlA2Ca1-xGdxCu2O7 (A=Ba,Sr). PMID- 9975108 TI - d-wave model for microwave response of high-Tc superconductors. PMID- 9975107 TI - Effect of Abrikosov-Gor'kov impurities on Raman shifts and changes in phonon widths. PMID- 9975109 TI - Superconductivity of the Pr-doped (Y,Eu)Ba2Cu4O8 system. PMID- 9975110 TI - Quantum statistical mechanics of vortices in high-temperature superconductors. PMID- 9975111 TI - Symmetry dependence of phonon line shapes in superconductors with anisotropic gaps. PMID- 9975112 TI - Energy cost associated with vortex crossing in superconductors. PMID- 9975113 TI - Bosonic high-Tc superconductivity in two dimensions. PMID- 9975114 TI - Discontinuity and quasitricritical behavior near Tc in ferroelectric triglycine selenate. PMID- 9975116 TI - Power-law eigenstates of a regular Vicsek fractal with hierarchical interactions. PMID- 9975115 TI - High-pressure transformations of C60 to diamond and sp3 phases at room temperature and to sp2 phases at high temperature. PMID- 9975117 TI - Interfacial quality and giant magnetoresistance in MBE-grown Co/Cu(111) superlattices. PMID- 9975119 TI - Mossbauer study of antiferromagnetic CuFeS2-xSex. PMID- 9975118 TI - Magnetic-polarization effect of Pd layers in Fe/Pd multilayers. PMID- 9975120 TI - Quantum Heisenberg model with long-range ferromagnetic interactions. PMID- 9975122 TI - Variations of Tc for changes in the spin-fluctuation spectral weight. PMID- 9975121 TI - Calculation of the low-spin and high-spin states of Ih Co13. PMID- 9975123 TI - Magnetic dynamic hysteresis of a resistively shunted Josephson-junction array. PMID- 9975125 TI - Metal-insulator transition and superconductivity in Y1-xPrxBa2Cu3O7. PMID- 9975124 TI - Unusual hole dependence of Tc in HgBa2CuO4+ delta. PMID- 9975127 TI - hcp-to-bcc pressure-induced transition in Mg simulated by ab initio molecular dynamics. PMID- 9975126 TI - Angular dependence of specular resonant nuclear scattering of x rays. PMID- 9975128 TI - Stability of carbon nitride solids. PMID- 9975129 TI - Glass-forming tendency, percolation of rigidity, and onefold-coordinated atoms in covalent networks. PMID- 9975130 TI - Enhancement of molecular interactions in strongly scattering dielectric composite optical media. PMID- 9975131 TI - Magnetoelastic behavior of NbSe3. PMID- 9975132 TI - Theoretical investigation of the orientation dependence of the magneto-optical Kerr effect in Co. PMID- 9975133 TI - Gap states, local moments, and magnetic dynamics in a Mott-Hubbard antiferromagnet doped with static impurities. PMID- 9975135 TI - High-field superconducting transition induced by correlated disorder. PMID- 9975134 TI - Spin softening in models with competing interactions: A high-anisotropy expansion to all orders. PMID- 9975136 TI - Two-dimensional angular-correlation-of-annihilation-radiation study of kappa (BEDT-TTF)2Cu(NCS)2. PMID- 9975138 TI - Effect of superconducting fluctuations on spin susceptibility and NMR relaxation rate. PMID- 9975137 TI - Tunneling spectroscopy into YBa2Cu4O8: Intralayer and interlayer analysis. PMID- 9975139 TI - Degenerate Anderson impurity model in the presence of spin-orbit and crystal field splitting. PMID- 9975141 TI - Resistance noise near the Anderson transition. PMID- 9975140 TI - Electronic structure of Bi2CuO4. PMID- 9975142 TI - Assignment of a photoemission feature in the O-2s-O-2p band gaps of TiO2 and V2O5. PMID- 9975143 TI - Angle-resolved soft-x-ray fluorescence and absorption study of graphite. PMID- 9975144 TI - Corrections to Migdal's theorem for spectral functions: A cumulant treatment of the time-dependent Green's function. PMID- 9975146 TI - Electronic excitations in 3d transition metals. PMID- 9975145 TI - Quantum Monte Carlo study of the one-dimensional Hubbard model with random hopping and random potentials. PMID- 9975147 TI - Fourth-order gradient corrections to the exchange-only energy functional: Importance of PMID- 9975148 TI - Excitonic n-string in linear chains: Electronic structure and optical properties. PMID- 9975149 TI - Simplified electronic-structure model for hydrogen-bonded systems: Water. PMID- 9975150 TI - Recursive diagonalization and analytical formulation of the scattering matrix for large-scale scattering problems. PMID- 9975151 TI - Density-functional approach to LCAO methods. PMID- 9975152 TI - Comparison of two cluster-expansion methods for the energetics of Pd-V alloys. PMID- 9975153 TI - Acceleration schemes for ab initio molecular-dynamics simulations and electronic structure calculations. PMID- 9975154 TI - Hall effect and conductivity in pyrite NiS2. PMID- 9975155 TI - Theory of the orbital Kondo effect with assisted hopping in strongly correlated electron systems: Parquet equations, superconductivity, and mass enhancement. PMID- 9975156 TI - Investigation of the Luttinger parameters for InP using hot-electron luminescence. PMID- 9975157 TI - Femtosecond photomodulation spectroscopy of a-Si:H and a-Si:Ge:H alloys in the midinfrared. PMID- 9975158 TI - Optically detected electron-nuclear double resonance of the S=1 excited state of the PGa-YP defect in GaP: The neighboring 31P and 69Ga and 71Ga shells. PMID- 9975159 TI - Bonding of H-CAs pairs in AlxGa1-xAs alloys. PMID- 9975160 TI - Spectroscopic ellipsometry study of Zn1-xCoxSe alloys grown on GaAs. PMID- 9975161 TI - Hydrogen diffusion in a-Si:H stimulated by intense illumination. PMID- 9975162 TI - Influence of electron-hole correlations on the absorption of GaAs in the presence of nonthermalized carriers. PMID- 9975163 TI - Splitting of the metastable EL2 acceptor state. PMID- 9975165 TI - Structural study of a-Si and a-Si:H films by EXAFS and Raman-scattering spectroscopy. PMID- 9975164 TI - Impurity-related photoluminescence from silicon at room temperature. PMID- 9975166 TI - Structural and optical properties of Zn1-xCdxGa2Se4 and Zn1-xCdxGa2Se4:Co2+ single crystals. PMID- 9975167 TI - Far-infrared spin resonance in the II-VI diluted magnetic semiconductors Zn1 xMnxSe, Cd1-xMnxSe, and Zn1-xCoxS. PMID- 9975168 TI - Resonant inter-valence-band Raman scattering of photoexcited holes in germanium. PMID- 9975169 TI - Effect of pressure on a defect-related band-resonant vibrational mode in implanation-disordered GaAs. PMID- 9975170 TI - Ultrafast relaxation of highly photoexcited carriers in p-type and intrinsic GaAs. PMID- 9975171 TI - Ab initio study of piezoelectricity and spontaneous polarization in ZnO. PMID- 9975172 TI - Calculated and measured uv reflectivity of SiC polytypes. PMID- 9975173 TI - Effective-medium tight-binding model for silicon. PMID- 9975174 TI - Bonding in the molybdenum silicides. PMID- 9975175 TI - Electronic properties of cubic and hexagonal SiC polytypes from ab initio calculations. PMID- 9975176 TI - Dynamics of singlet excitations in conjugated polymers: Poly(phenylenevinylene) and poly(phenylphenylenevinylene). PMID- 9975177 TI - Quasiparticle band structures of six II-VI compounds: ZnS, ZnSe, ZnTe, CdS, CdSe, and CdTe. PMID- 9975178 TI - Network models of quantum percolation and their field-theory representations. PMID- 9975179 TI - Correlation energy of a two-dimensional electron gas. PMID- 9975180 TI - Theoretical studies of halogen-semiconductor-surface interactions: The Cl/GaAs(110) system. PMID- 9975181 TI - Thermal-mismatch-strain relaxation in epitaxial CaF2, BaF2/CaF2, and PbSe/BaF2/CaF2 layers on Si(111) after many temperature cycles. PMID- 9975183 TI - Conductance quantization in a periodically modulated channel. PMID- 9975182 TI - Surfactant-mediated growth of Ge on Si(111). PMID- 9975185 TI - Electron band structure in a two-dimensional periodic magnetic field. PMID- 9975184 TI - Surface morphology of Pb overlayers grown on Si(100)-(2 x 1). PMID- 9975186 TI - Femtosecond spin spectroscopy in magnetically tunable heterostructures. PMID- 9975187 TI - Magnetoconductance of a nanoscale antidot. PMID- 9975188 TI - Density of states for double-barrier quantum-well structures under the influence of external fields and phase-breaking scattering. PMID- 9975189 TI - Exciton dynamics in GaAs quantum wells under resonant excitation. PMID- 9975190 TI - Electronic structure of the arsenic-passivated Si(111) surface. PMID- 9975191 TI - Surface states and reconstruction of epitaxial sqrt 3 x sqrt 3 R30 degrees Er silicide on Si(111). PMID- 9975192 TI - Evaluation of various approximations used in the envelope-function method. PMID- 9975194 TI - Metallization, surface photovoltage, and quantum-well-type resonance for K covered Si(100) observed via valence-band photoemission. PMID- 9975193 TI - Single-monolayer ordered phases of C60 molecules on Si(111)-(7 x 7) surfaces. PMID- 9975195 TI - Model for the Pb center at the (111) Si/SiO2 interface. PMID- 9975196 TI - Far-infrared radiation-induced inter-edge-channel scattering in a high magnetic field. PMID- 9975197 TI - Low-temperature growth on Si(111) substrates. PMID- 9975199 TI - Exciton binding energies in a dielectric quantum well in a magnetic field. PMID- 9975198 TI - Stabilization of the asymmetric Ge dimer on Si(100) by charge transfer. PMID- 9975200 TI - Infrared-absorption spectra of acceptors confined in GaAs/AlxGa1-xAs quantum wells in the presence of an external magnetic field. PMID- 9975201 TI - First-principles calculations of (GaP)m/(AlP)n superlattices. PMID- 9975202 TI - Electromodulation spectroscopy of an array of modulation-doped GaAs/Ga1-xAlxAs quantum dots: Experiment and theory. PMID- 9975203 TI - Confined and interface acoustic phonons in a quantum wire. PMID- 9975204 TI - Exchange interaction in quantum-wire subbands. PMID- 9975205 TI - Atomic-scale imperfections and fluctuations in the transmission properties of a quantum dot. PMID- 9975206 TI - Competition between thermally induced resonant tunneling and phonon-assisted tunneling in semiconductor superlattices. PMID- 9975208 TI - Conductance and conductance fluctuations of narrow disordered quantum wires. PMID- 9975207 TI - Correlations in coupled layers of electrons and holes. PMID- 9975210 TI - Microscopic-balance-equation theory of the real-space transfer in semiconductor multiple quantum wells. PMID- 9975209 TI - Charged spin-texture excitations and the Hartree-Fock approximation in the quantum Hall effect. PMID- 9975211 TI - Laser-stimulated nonthermal particle emission from InP and GaAs surfaces. PMID- 9975213 TI - Suppression of the Josephson effect by quantum fluctuations in the fractional quantum Hall state. PMID- 9975212 TI - Electroluminescence study of resonant tunneling in GaAs-AlAs superlattices. PMID- 9975214 TI - Layer-by-layer resolved core-level shifts in CaF2 and SrF2 on Si(111): Theory and experiment. PMID- 9975215 TI - Interfacial reaction of C60 with silver. PMID- 9975216 TI - Structural analysis of the nitrogen-adsorbed NbC(111) surface. PMID- 9975217 TI - Reintroduction of ionic structure in the self-consistent jellium model for metal clusters: Pseudopotential perturbation theory. PMID- 9975218 TI - Adsorption-isotherm study of monolayer films of N2 on BN. PMID- 9975219 TI - Surface band structures on Nb(001). PMID- 9975220 TI - Ag-Au superlattice band structure. PMID- 9975221 TI - Simulations of length-scale change for finger growth in intercalation compounds. PMID- 9975222 TI - Dynamic scaling of island-size distribution in submonolayer growth of 1 x 1 films. PMID- 9975223 TI - Structures of surfaces and amorphous samples obtained by EXAFS measurements in the x-ray Raman-scattering mode. PMID- 9975224 TI - Anharmonicity but absence of surface melting on Al(001). PMID- 9975225 TI - Interference, resonances, and bound states at the Pd(001) and Rh(001) surfaces. PMID- 9975226 TI - Surface melting and layering transitions from a lattice-gas model. PMID- 9975227 TI - Surface dielectric response of uniaxial crystals: Application to graphite. PMID- 9975228 TI - Adatom yields, sputtering yields, and damage patterns of single-ion impacts on Pt(111). PMID- 9975229 TI - Molecular-dynamics simulation of adatom formation under keV-ion bombardment of Pt(111). PMID- 9975230 TI - Total-energy calculations using a gradient-expanded kinetic-energy functional. PMID- 9975231 TI - Electron-phonon interaction in one dimension: Exact spectral properties. PMID- 9975232 TI - Fermi surface of noble metals: Full-potential generalized-gradient-approximation calculations. PMID- 9975233 TI - Edge magnetoplasmons of two-dimensional electron-gas systems. PMID- 9975235 TI - Anomalous magnetoresistance plateaus of an H-shaped quantum wire. PMID- 9975234 TI - Measurement of the direct energy gap of Al0.5In0.5P: Implications for the band discontinuity at Ga1-xInxP/AlyIn1-yP heterojunctions. PMID- 9975236 TI - Hierarchy theory of the fractional quantum Hall effect: Two physically equivalent formulations. PMID- 9975237 TI - Metastable oxygen-induced ordered structure on the Si(001) surface. PMID- 9975238 TI - Reconstruction on Si(100) surfaces. PMID- 9975239 TI - Second-harmonic generation from SiO2/Si(111) interfaces. PMID- 9975240 TI - Theoretical simulation of scanning-tunneling-microscopy images of the GaAs(001) beta (2 x 4) and beta (4 x 2) surfaces. PMID- 9975241 TI - Impurity states in doubly doped systems: Investigation of donor-donor and donor acceptor pairs. PMID- 9975242 TI - Hysteresis in the low-temperature photoconductivity of C60 films. PMID- 9975243 TI - Low-angle neutron and x-ray scattering of hydrogenated and deuterated Mo/V superlattices. PMID- 9975244 TI - Mode-locking hysteresis in the globally coupled model of charge-density waves. PMID- 9975245 TI - Optical properties of beta -C3N4 and its pressure dependence. PMID- 9975247 TI - Band dispersion in C60(111): An angle-resolved photoemission study. PMID- 9975246 TI - Skutterudite antimonides: Quasilinear bands and unusual transport. PMID- 9975248 TI - Photoinduced charge transfer in poly(p-phenylene vinylene). PMID- 9975250 TI - Exciton binding energies in shallow GaAs-AlyGa1-yAs quantum wells. PMID- 9975249 TI - Vacancy defects in photoexcited GaAs studied by positron two-dimensional angular correlation of annihilation radiation. PMID- 9975251 TI - Control of single-electron tunneling by surface acoustic waves. PMID- 9975253 TI - Conductance distribution of a quantum dot with nonideal single-channel leads. PMID- 9975252 TI - Influence of the electron-hole spatial separation on the magnetoluminescence measurements of the fractional-quantum-Hall-effect energy gaps. PMID- 9975254 TI - Statistics of fluctuations of wave functions of chaotic electrons in a quantum dot in an arbitrary magnetic field. PMID- 9975255 TI - Kinetics of surfactant-mediated epitaxial growth. PMID- 9975256 TI - Atomic imaging by x-ray-fluorescence holography and electron-emission holography: A comparative theoretical study. PMID- 9975257 TI - Conduction-electron effect in quantum tunneling diffusion of hydrogen on metal surfaces. PMID- 9975258 TI - Initial stage of oxygen chemisorption on Na/Pt and Na/Cr: An autoionization electron-spectroscopy study. PMID- 9975259 TI - Erratum: Photoacoustic investigation of the quantum size effect and thermal properties in ZrO2 nanoclusters PMID- 9975260 TI - Spin-charge separation at small length scales in the two-dimensional t-J model. PMID- 9975261 TI - Localization and mobility edges in one-dimensional deterministic potentials. PMID- 9975263 TI - Alloying effects of Kondo insulators. PMID- 9975262 TI - Doping dependence of Ni 2p x-ray-absorption spectra of MxNi1-xO (M=Li,Na). PMID- 9975264 TI - Resonant photoemission study of CeO2. PMID- 9975265 TI - Charge-transfer effect on the linewidth of Fe K alpha x-ray fluorescence spectra. PMID- 9975266 TI - Higher-order finite-difference pseudopotential method: An application to diatomic molecules. PMID- 9975267 TI - Critical and bicritical properties of Harper's equation with next-nearest neighbor coupling. PMID- 9975268 TI - Falicov-Kimball model and its relation to the Hubbard model: Studies on clusters. PMID- 9975269 TI - Dielectric response in insulators: A wave-vector- and frequency-dependent model. PMID- 9975270 TI - Optical reflectivity and Raman spectra of Sr2FeO4 under pressure. PMID- 9975271 TI - Statistical properties and statistical interaction for particles with spin: The Hubbard model in one dimension and a statistical spin liquid. PMID- 9975272 TI - Mechanism of spin and charge separation in one-dimensional quantum antiferromagnets. PMID- 9975273 TI - Charge gap in the one-dimensional dimerized Hubbard model at quarter-filling. PMID- 9975274 TI - Interacting electrons on a square Fermi surface. PMID- 9975275 TI - Electronic structures of disordered Ag-Mg alloys. PMID- 9975276 TI - Magnetic ground-state properties and spectral distributions. I. X-ray-absorption spectra. PMID- 9975277 TI - Magnetic ground-state properties and spectral distributions. II. Polarized photoemission. PMID- 9975278 TI - Absorption-edge singularities for a nonequilibrium Fermi sea. I. Second-order perturbation theory. PMID- 9975279 TI - Absorption-edge singularities for a nonequilibrium Fermi sea. II. Second-order diagrammatic expansion. PMID- 9975280 TI - Observation of time-nonreversible optical interaction with zinc-blende semiconductors. PMID- 9975281 TI - Linear and nonlinear optical properties of four polytypes of SiC. PMID- 9975282 TI - Exciton self-trapping at an isoelectronic center in silicon. PMID- 9975283 TI - Interpretation of infrared data in neutron-irradiated silicon. PMID- 9975285 TI - Electronic structure of the SbGa heteroantisite defect in GaAs:Sb. PMID- 9975286 TI - Up to fifth-order Raman scattering of InP under nonresonant conditions. PMID- 9975284 TI - Structure of a-Si1-xCx:H alloys by wide-angle x-ray scattering: Detailed determination of first- and second-shell environment for Si and C atoms. PMID- 9975288 TI - Valence-band density of states of near-noble-metal (Ni,Pd,Pt) monosilicides by using soft-x-ray-emission spectroscopy. PMID- 9975287 TI - Small-bipolaron hopping conductivity in chalcogenide glasses. PMID- 9975289 TI - Quantum magnetotransport in a nondegenerate two-dimensional electron gas under extremely strong magnetic fields. PMID- 9975290 TI - Transferable nonorthogonal tight-binding scheme for silicon. PMID- 9975291 TI - Density dependence of electron scattering at low density. PMID- 9975292 TI - Pulsed-light soaking of hydrogenated amorphous silicon. PMID- 9975293 TI - Quantum Monte Carlo calculations of phonon-assisted luminescence from polyexcitons in Si. PMID- 9975294 TI - Temperature and many-body effects on the intersubband transition in a GaAs/Al0.3Ga0.7As multiple quantum well. PMID- 9975295 TI - Exciton formation and hole-spin relaxation in intrinsic quantum wells. PMID- 9975296 TI - Quantum waveguide transport in serial stub and loop structures. PMID- 9975297 TI - Strain relief by microroughness in surfactant-mediated growth of Ge on Si(001). PMID- 9975298 TI - Infrared and Raman studies on a-Ge1-xSnx:H thin films. PMID- 9975299 TI - Mechanism of apparent reflection of electrons from extra probes investigated by the magnetic electron-focusing effect. PMID- 9975300 TI - Surface-potential dependence of interface-state passivation in metal-tunnel-oxide silicon diodes. PMID- 9975301 TI - Reflectivity and photoluminescence measurements in ZnS epilayers grown by metal organic chemical-vapor deposition. PMID- 9975302 TI - Barrier height versus confinement efficiency for the optical phonons in GaAs/AlxGa1-xAs heterostructures. PMID- 9975303 TI - Critical layer thickness for self-assembled InAs islands on GaAs. PMID- 9975304 TI - Theoretical investigations of resonant tunneling in asymmetric multibarrier semiconductor heterostructures in an applied constant electric field. PMID- 9975306 TI - Magnetoluminescence studies in GaAs-AlxGa1-xAs single heterojunctions: Observation of parity-forbidden Landau-level transitions. PMID- 9975305 TI - Continuum model of the optical modes of vibration of an ionic crystal slab. PMID- 9975307 TI - Currents in the compressible and incompressible regions of the two-dimensional electron gas. PMID- 9975308 TI - Lack of band-offset transitivity for semiconductor heterojunctions with polar orientation: ZnSe-Ge(001), Ge-GaAs(001), and ZnSe-GaAs(001). PMID- 9975309 TI - Defect-excitation processes involved in laser-induced atomic emission and laser ablation of nonmetallic solids. PMID- 9975310 TI - Modeling of electroabsorption in semiconductor quantum structures within the eight-band k PMID- 9975312 TI - Dispersion of GaAs(110) surface phonons measured with HREELS. PMID- 9975311 TI - Lateral subband transitions in the luminescence spectra of a one-dimensional electron-hole plasma in In0.53Ga0.47As/InP quantum wires. PMID- 9975313 TI - Spin-flip Raman scattering in CdTe/Cd1-xMnxTe multiple quantum wells: A model system for the study of electron-donor binding in semiconductor heterostructures. PMID- 9975315 TI - Final-state excitations in the photoluminescence spectra of InxGa1-xAs-InP quantum wells at low and high carrier density. PMID- 9975314 TI - Langevin molecular dynamics with quantum forces: Application to silicon clusters. PMID- 9975316 TI - Phonons in the quantum Hall effect: A nonlinear-dynamics picture. PMID- 9975318 TI - Tetrahedron-model analysis of silicon nitride thin films and the effect of hydrogen and temperature on their optical properties. PMID- 9975317 TI - Evidence of one-dimensional excitons in GaAs V-shaped quantum wires. PMID- 9975319 TI - Exciton thermalization in quantum-well structures. PMID- 9975320 TI - Cathodoluminescence imaging of quantum wells: The influence of exciton transfer on the apparent island size. PMID- 9975321 TI - Dynamics and spin relaxation of excitons in GaAs/AlxGa1-xAs quantum wells. PMID- 9975322 TI - Improved modeling of excitons in type-II semiconductor heterostructures by use of a three-dimensional variational function. PMID- 9975324 TI - In-plane birefringence of GaAs/AlAs multiple quantum wells. PMID- 9975323 TI - Calculation of Raman scattering by acoustic phonons in superlattices. PMID- 9975325 TI - Edge states of composite fermions. PMID- 9975326 TI - Quantum-mechanical evolution of real-space transfer. PMID- 9975328 TI - Doping-profile effects on the tunneling times of electrons confined in double barrier heterostructures. PMID- 9975327 TI - Electromagnetic absorption in finite systems and the crossover to macroscopic behavior. PMID- 9975330 TI - Nonadiabatic particle transport in a one-dimensional electron system. PMID- 9975329 TI - Magneto-optical spectroscopy of free- and bound-electron-hole excitations in the presence of a two-dimensional electron gas. PMID- 9975331 TI - Quantum study of magnetotransport in antidot superlattices. PMID- 9975332 TI - Four-wave mixing and terahertz emission from three-level systems in quantum wells: Effects of inhomogeneous broadening. PMID- 9975333 TI - Theoretical study of Cl adsorption on the GaAs(110) surface. PMID- 9975334 TI - Inversion asymmetry, hole mixing, and enhanced Pockels effect in quantum wells and superlattices. PMID- 9975335 TI - Electronic properties and valence-band offset of strained ZnTe/CdTe (001) superlattices. PMID- 9975336 TI - Edge-state properties and bulk eigenenergy spectra of periodically modulated two dimensional electron systems in a magnetic field. PMID- 9975337 TI - Low-temperature electronic transport properties in thin films of Pd and PdH0.3. PMID- 9975338 TI - Relaxation process of charge transfer in C60. PMID- 9975339 TI - Growth mode and electronic structure of the epitaxial C60(111)/GeS(001) interface. PMID- 9975340 TI - Electrostatic potentials for metal-oxide surfaces and interfaces. PMID- 9975342 TI - Electronic and geometrical structure of rutile surfaces. PMID- 9975341 TI - Simulation of surface segregation free energies. PMID- 9975343 TI - Unoccupied electronic structure of Al(111). PMID- 9975345 TI - Absence of photoinduced electron transfer from the excitonic electron-hole bound state in polydiacetylene conjugated polymers. PMID- 9975344 TI - Staging and interlayer interaction in the misfit-layer compounds (RS)nNbS2 (R=La,Ce; n=0.6,1.2) studied by Raman and infrared spectroscopies. PMID- 9975346 TI - Controlled synthesis and quantum-size effect in gold-coated nanoparticles. PMID- 9975347 TI - Theoretical study of the orientational epitaxy of the reconstructed (001) surfaces of Au and Pt. PMID- 9975348 TI - Electronic properties of ultrathin Cu and Fe films on TiO2(110) studied by photoemission and inverse photoemission. PMID- 9975350 TI - Electron-momentum spectroscopy of the core state of solid carbon. PMID- 9975351 TI - Surface anharmonicities and disordering on Ni(100) and Ni(110). PMID- 9975349 TI - Effective-medium theory for the optical properties of diamond and diamondlike films. PMID- 9975352 TI - Anisotropy of diffusion along steps on the (111) faces of gold and silver. PMID- 9975353 TI - Surface core-level shifts for simple metals. PMID- 9975354 TI - Brillouin scattering from shear horizontal surface phonons in silicon on insulator structures: Theory and experiment. PMID- 9975355 TI - Equilibrium surface segregation of interstitials on bcc(001) surfaces: A lattice gas approach. PMID- 9975356 TI - Electronic correlation effects in a fullerene molecule studied by the variational Monte Carlo method. PMID- 9975357 TI - Effects of orbital nonorthogonality on band structure within the tight-binding scheme. PMID- 9975358 TI - Partition functions for strongly correlated fermion systems. PMID- 9975359 TI - Wentzel-Bardeen singularity and phase diagram for interacting electrons coupled to acoustic phonons in one dimension. PMID- 9975360 TI - Stacking-fault excitons in AgBr microcrystals with twin planes. PMID- 9975361 TI - Alloy-assisted Auger recombination in ternary III-V compounds. PMID- 9975363 TI - Binding and transition energies of off-center D- impurity states in quantum wells and magnetic fields. PMID- 9975362 TI - Optical spectroscopic studies of InAs layer transformation on GaAs surfaces. PMID- 9975364 TI - Photocurrent spectroscopy of Zn1-xCdxSe/ZnSe quantum wells in p-i-n heterostructures. PMID- 9975365 TI - Edge-dislocation intersections in diamond cubic crystals. PMID- 9975367 TI - Short-wavelength phonon emission from a metal-semiconductor interface. PMID- 9975366 TI - Resistance fluctuations in diffusive transport at high magnetic fields in narrrow Si transistors. PMID- 9975369 TI - Interference oscillations of the acoustic phonon-assisted magnetotunneling in double quantum wells. PMID- 9975368 TI - Rate of electron tunneling in double quantum wells with nonideal interfaces. PMID- 9975370 TI - Electronic properties of semiconducting graphitic microtubules. PMID- 9975371 TI - Vibrational spectra of multishell fullerenes. PMID- 9975372 TI - d4 identification of the satellite in the Mn 3d photoemission spectra of Cd1 xMnxTe alloys. PMID- 9975373 TI - Comment on "Adsorption of C60 on Ta(110): Photoemission and C K-edge studies" PMID- 9975374 TI - Correlation between broad-band noise and frequency fluctuations of narrow-band noise in the charge-density wave in NbSe3. PMID- 9975375 TI - Observation of a fluctuating charge-density wave in the unoccupied electronic structure of (TaSe4)2I. PMID- 9975376 TI - Phonon-induced nonmetal-metal transition of a doped polyaniline. PMID- 9975379 TI - Association of a zero-bias anomaly in electron tunneling in AlxGa1-xAs with the DX defect. PMID- 9975377 TI - Origin of multiple-peak photoluminescence spectra of light-emitting porous silicon. PMID- 9975378 TI - Ab initio molecular-dynamics simulations of Si clusters using the higher-order finite-difference-pseudopotential method. PMID- 9975380 TI - Cyclotron-resonance oscillations in a two-dimensional electron-hole system. PMID- 9975382 TI - Orientation relationship of aligned carbon-hydrogen complexes in GaAs formed by the decomposition of trimethylgallium to the directions of the (2 x 4) surface reconstruction observed during growth. PMID- 9975381 TI - Structural determination of the Si(111) sqrt 3 x sqrt 3-Bi surface by x-ray standing waves and scanning tunneling microscopy. PMID- 9975383 TI - Conductance fluctuations in periodic antidot arrays. PMID- 9975384 TI - Adsorbate symmetry and Fermi resonances of methoxide adsorbed on Mo(110) as studied by surface infrared spectroscopy. PMID- 9975385 TI - Low-temperature scanning-tunneling-microscopy observations of the Si(001) surface with a low surface-defect density. PMID- 9975386 TI - Structure of D2 in zeolite. PMID- 9975387 TI - Optical properties of zoisite. PMID- 9975388 TI - Melting and melt structure of MgO at high pressures. PMID- 9975389 TI - Time-resolved fragmentation cross-section simulation of C60++C60 collisions. PMID- 9975390 TI - Electronic structure and structural phase stability in BaS, BaSe, and BaTe. PMID- 9975391 TI - EPR and optical studies of Co2+ ions in MgO from local-spin-density molecular orbital calculations. PMID- 9975392 TI - Lifetime effect on the multiplet structure of 4d x-ray-photoemission spectra in heavy rare-earth elements. PMID- 9975393 TI - Rearrangements in model face-centered-cubic solids. PMID- 9975394 TI - Relaxation rate of conserved and nonconserved order parameters in replacive transitions. PMID- 9975395 TI - Dynamics of the IR-to-blue wavelength upconversion in Pr3+-doped yttrium aluminum garnet and LiYF4 crystals. PMID- 9975396 TI - Thickness dependence of the dielectric susceptibility of ferroelectric thin films. PMID- 9975397 TI - High-pressure x-ray diffraction on potassium and rubidium up to 50 GPa. PMID- 9975398 TI - Microstructural defects in nanocrystalline iron probed by x-ray-absorption spectroscopy. PMID- 9975399 TI - Dislocation loops in finite systems. PMID- 9975400 TI - Atomic structure of amorphous Al100-2xCoxCex (x=8, 9, and 10) and Al80Fe10Ce10 alloys: An XAFS study. PMID- 9975401 TI - Ordered and disordered phases in Al-Ni-Co decagonal quasicrystals. PMID- 9975403 TI - Structural trends in amorphous carbon. PMID- 9975402 TI - Observation of the freezing line in a deuteron glass. PMID- 9975404 TI - Effect of the zero-point rotational motions on the quadrupolar glass order parameter in solid hydrogen. PMID- 9975405 TI - Mean-field theory for alkali-metal-doped polyacetylene. PMID- 9975406 TI - Binary tiling quasicrystals and matching rules. PMID- 9975407 TI - Theory of electromigration failure in polycrystalline metal films. PMID- 9975408 TI - Thermally stimulated polarization-depolarization current and polarization conductivity in ionically conducting glasses. PMID- 9975409 TI - Vibrational analysis of polyaniline: A comparative study of leucoemeraldine, emeraldine, and pernigraniline bases. PMID- 9975410 TI - Hopping theory of heat transport in disordered systems. PMID- 9975411 TI - Spatial disorder dependence of the conductance of a random resistor network. PMID- 9975412 TI - One-dimensional bipolaron in the strong-coupling limit. PMID- 9975413 TI - Magnetocrystalline anisotropy of 3d-4f intermetallics: Breakdown of the linear theory. PMID- 9975414 TI - Magnetic-susceptibility and heat-capacity measurements on PrRhSb. PMID- 9975415 TI - Cluster Monte Carlo dynamics for the antiferromagnetic Ising model on a triangular lattice. PMID- 9975416 TI - Magnetic properties of Cu80Co20 and Cu80Co15Fe5 melt-spun ribbons. PMID- 9975417 TI - Phase boundaries in ultrathin magnetic films. PMID- 9975418 TI - Magnetic properties of CocNi1-cCl2-FeCl3 graphite bi-intercalation compounds. PMID- 9975419 TI - Thickness-dependent oscillation of the magneto-optical properties of Au sandwiched (001) Fe films. PMID- 9975420 TI - Magnetic behavior of dilute Rh impurities in Au1-xFex alloys: A perturbed-angular correlation study. PMID- 9975421 TI - Competition between the Glauber and Kawasaki dynamics in the antiferromagnetic Ising model. PMID- 9975422 TI - Elementary excitation spectrum for the multichannel Kondo model at finite temperatures. PMID- 9975423 TI - Thermal contraction at the spin-Peierls transition in CuGeO3. PMID- 9975425 TI - Magnetic and magnetoelastic properties in tetragonal TbPO4. PMID- 9975424 TI - Crystal field and Kondo effects in CeCu6 and CeAl3. PMID- 9975426 TI - Role of hydrogen-sublattice ordering for magnetic and metal-semiconductor transitions in beta -HoH2+x. PMID- 9975427 TI - Dynamics of Ising spin glasses above the freezing temperature. PMID- 9975428 TI - Mean-field theory for critical phenomena in bilayer systems. PMID- 9975429 TI - Magnetic phase diagram of (DyxGd1-x)Fe11Ti alloys. PMID- 9975430 TI - Mossbauer, magnetic, and electronic-structure studies of YFe12-xMox compounds. PMID- 9975432 TI - Ruderman-Kittel-Kasuya-Yosida polarization in some inhomogeneous situations. PMID- 9975431 TI - Orbital and spin sum rules in x-ray magnetic circular dichroism. PMID- 9975433 TI - Numerical studies of the two-dimensional XY model with symmetry-breaking fields. PMID- 9975434 TI - Renormalization-group analysis of long-range order in the two-dimensional antiferromagnetic Heisenberg model. PMID- 9975435 TI - Collective-variable approach to the dynamics of nonlinear magnetic excitations with application to vortices. PMID- 9975436 TI - Slow quantum oscillations in the semimetallic spin-density-wave state of tetramethyltetraselenafulvalinium nitrate (TMTSF)2NO3. PMID- 9975438 TI - Bosonization in two dimensions: A space-time tunneling approach. PMID- 9975437 TI - High-field magnetoresistance of the Bechgaard salt (TMTSF)2NO3: Quantum oscillations in the spin-density-wave state and phase transitions. PMID- 9975439 TI - Quantum and classical behavior of single-particle dynamics in dense liquid 4He. PMID- 9975440 TI - Specific heat of the organic superconductor kappa -(BEDT-TTF)2I3. PMID- 9975441 TI - Structural effects of hydrostatic pressure in Sr1-xMxCuO2 (M=La,Ca) and Sr4Cu6O10. PMID- 9975442 TI - Fulde-Ferrell state in quasi-two-dimensional superconductors. PMID- 9975443 TI - Proximity effect and charging in mesoscopic normal-metal-superconductor junction systems. PMID- 9975444 TI - Thermal depinning of a single superconducting vortex in Nb. PMID- 9975445 TI - Calculations of the superconducting critical temperature with vertex corrections. PMID- 9975447 TI - Fluxon-density waves in a modulated Josephson ring. PMID- 9975446 TI - Josephson effect in nanoscopic structures. PMID- 9975448 TI - Long Josephson junctions driven by biharmonic signals. PMID- 9975449 TI - Influence of the environment on charge quantization in small superconducting islands. PMID- 9975450 TI - Properties of an electron bubble approaching the surface of liquid helium. PMID- 9975451 TI - Time-dependent equations for phase differences and a collective mode in Josephson coupled layered superconductors. PMID- 9975452 TI - Temperature derivative of the superfluid density and flux quantization as criteria for superconductivity in two-dimensional Hubbard models. PMID- 9975453 TI - Phase locking of Fiske modes in sine-Gordon systems. PMID- 9975454 TI - Flux phase, Neel antiferromagnetism, and superconductivity in the t-J model. PMID- 9975455 TI - Theory of electron-hole asymmetry in doped CuO2 planes. PMID- 9975456 TI - Origin of the Tc depression and the role of charge transfer and dimensionality in ultrathin YBa2Cu3O7- delta. PMID- 9975458 TI - Damping of spin waves for a doped antiferromagnet. PMID- 9975457 TI - Evolution of hole and magnon spectra of the two-dimensional t-J model with doping. PMID- 9975459 TI - Theory and experiment on electromagnetic-wave-propagation velocities in stacked superconducting tunnel structures. PMID- 9975460 TI - q dependence of the dynamic susceptibility chi "(q, omega ) in superconducting YBa2Cu3O6.6 (Tc=46 K). PMID- 9975461 TI - Phase-slip dissipation and dimensionality above the irreversibility line in Bi2Sr2CaCu2O8+x. PMID- 9975462 TI - Estimation of the doping dependence of the Neel temperature in high-Tc copper oxides. PMID- 9975464 TI - Resistive transition for YBa2Cu3O7- delta -Y2BaCuO5 composites: Influence of a magnetic field. PMID- 9975463 TI - Influence of hole doping on spin dynamics in lightly doped copper oxide superconductors. PMID- 9975465 TI - Quasi-two-dimensional vortex-glass transition observed in epitaxial Bi2Sr2Ca2Cu3Ox thin films. PMID- 9975466 TI - Elementary physical properties and crystal structures of LaRh2B2C and LaIr2B2C. PMID- 9975467 TI - Measurements of 3d occupancy from Cu L2,3 electron-energy-loss spectra of rapidly quenched CuZr, CuTi, CuPd, CuPt, and CuAu. PMID- 9975468 TI - Influence of inelastic interactions on the angular distribution of 2-keV electrons. PMID- 9975469 TI - Spectral response of the orientational glass Ar1-x(N2)x. PMID- 9975470 TI - Order and disorder in Ni3V: Effective pair interactions and the role of electronic excitations. PMID- 9975472 TI - Optical free-induction decay in fractal clusters. PMID- 9975471 TI - Temperature-induced amorphization of SiO2 stishovite. PMID- 9975473 TI - Scaling properties of the ferromagnetic state in the Hubbard model. PMID- 9975475 TI - Giant magnetoresistance in hybrid magnetic nanostructures including both layers and clusters. PMID- 9975474 TI - Large low-temperature magnetoresistance in weakly spin-correlated CeCu2Sn2 and CeNi2Sn2. PMID- 9975476 TI - Mean-field phase diagrams of AT2X2 compounds. PMID- 9975477 TI - NMR relaxation in half-integer antiferromagnetic spin chains. PMID- 9975478 TI - Magnetic structure of Gd2CuO4: Low-temperature anomalies in ac susceptibility. PMID- 9975480 TI - Doping dependence of the susceptibility in the two-dimensional Hubbard model close to half-filling. PMID- 9975479 TI - Quantum liquid of vortices in superconductors at T=0. PMID- 9975481 TI - Binding of holes to magnetic impurities in a strongly correlated system. PMID- 9975482 TI - Effect of sample shape on the low-field peak in the magnetization of YBa2Cu3O7- delta. PMID- 9975483 TI - Magnetic irreversibility in Bi2Sr2CaCu2O8 fibers irradiated by neutrons. PMID- 9975484 TI - 1s x-ray-absorption spectroscopy of C60: The effects of screening and core-hole relaxation. PMID- 9975485 TI - Interatomic force constants from first principles: The case of alpha -quartz. PMID- 9975486 TI - Successive structural phase transitions in a hexagonal linear-chain ferroelectric crystal RbMnBr3. PMID- 9975487 TI - Reversible pressure-induced structural transitions between metastable phases of silicon. PMID- 9975489 TI - Time decay of the remanent magnetization in TDAE-C60. PMID- 9975488 TI - Structure of GaSb to 35 GPa. PMID- 9975490 TI - Spin-dependent transmission of low-energy electrons through ultrathin magnetic layers. PMID- 9975492 TI - Anisotropic spin diffusion in a saturated 3He-4He solution. PMID- 9975491 TI - Influence of the magnetic-layer thickness on the interlayer exchange coupling: Competition between oscillation periods. PMID- 9975493 TI - Electric-field tuning of the superconductor-insulator transition in granular Al films. PMID- 9975494 TI - Onset of ferromagnetic exchange in adsorbed 3He films. PMID- 9975495 TI - Discontinuity in the low-field magnetization of single-crystal Tl2Ba2CuO6 with H||||ab. PMID- 9975496 TI - Erratum: Nonadiabatic small-polaron hopping conduction in Li-doped and undoped Bi4Sr3Ca3CuyOx (0 <= y <= 5) PMID- 9975497 TI - Acoustic velocities and refractive index of SiO2 glass to 57.5 GPa by Brillouin scattering. PMID- 9975498 TI - Elastic properties of B2-NiTi and B2-PdTi. PMID- 9975499 TI - Scaling in ferroelectrics with critical points induced by an electric field. PMID- 9975500 TI - Complete elastic moduli of La2-xSrxCuO4 (x=0.00 and 0.14) near the tetragonal orthorhombic structural phase transition. PMID- 9975501 TI - Pressure-induced kinetics of ferroelectric phase transitions. PMID- 9975502 TI - Photoelectric domain structure in ruby: Studies with electric-field modulation of photon echo. PMID- 9975504 TI - Direct observation of spontaneous strain variation and domain evolution in the phase transition of NdP5O14. PMID- 9975503 TI - Laser-field-induced superionic transition. PMID- 9975505 TI - Thermal hysteresis effects in the ferroelectric-ferroelastic phase transition in PMID- 9975506 TI - Evidence of anomalous hopping and tunneling effects on the conductivity of a fractal Pt-film system. PMID- 9975508 TI - Theory of the crystal structures of selenium and tellurium: The effect of generalized-gradient corrections to the local-density approximation. PMID- 9975507 TI - Nature of the ferroelectric phase transition in PbTiO3. PMID- 9975509 TI - Evidence for the crossover process after optical excitation of the F center in NaI. PMID- 9975510 TI - Influence of ion-electron interaction on the formation mechanism of depleted zones in displacement cascades in metals. PMID- 9975511 TI - Computer simulations of disordering kinetics in irradiated intermetallic compounds. PMID- 9975513 TI - Identification of a hyperlattice of a quasiperiodic structure based on experimental observations. PMID- 9975512 TI - Molecular dynamics of ferroelectric polymeric systems as studied by incoherent quasielastic neutron scattering. PMID- 9975514 TI - Conformational and electronic properties of flexible conducting polymer chains. PMID- 9975515 TI - Reverse Monte Carlo study of structure changes in amorphous Pd52Ni32P16 upon annealing. PMID- 9975516 TI - Dielectric measurement of the model glass transition in orientationally disordered cyclo-octanol. PMID- 9975517 TI - Estimation of the free-charge-carrier concentration in fast-ion conducting Na2S B2S3 glasses from an analysis of the frequency-dependent conductivity. PMID- 9975519 TI - Renormalization-group analysis of extended electronic states in one-dimensional quasiperiodic lattices. PMID- 9975518 TI - Augmented-space recursive method for the study of short-ranged ordering effects in binary alloys. PMID- 9975520 TI - Correlated atomic motions in glassy selenium. PMID- 9975521 TI - Defect-induced Raman spectra in doped CeO2. PMID- 9975522 TI - Interaction of a group of dislocations within the framework of the continuum Frenkel-Kontorova model. PMID- 9975523 TI - Interimpurity transfer in condensed media: Breakdown of coherent tunneling and conditions for the creation of localized states. PMID- 9975524 TI - Percolation effects in two-component nonlinear composites: Crossover from linear to nonlinear behavior. PMID- 9975525 TI - Interdiffusion and free-boundary problem for r-component (r >= 2) one-dimensional mixtures showing constant concentration. PMID- 9975526 TI - Inelastic-neutron-scattering study of phonon eigenvectors and frequencies in Si. PMID- 9975528 TI - Transition between bipolaron and polaron states in doped heterocycle polymers. PMID- 9975527 TI - Lattice dynamics and hyperfine interactions in ZnF2 single crystals. PMID- 9975529 TI - Quantum electrodynamics of resonant energy transfer in condensed matter. II. Dynamical aspects. PMID- 9975530 TI - Lattice dynamics and dielectric properties of incipient ferroelectric TiO2 rutile. PMID- 9975531 TI - Concentration dependence of the conductivity and diffusivity in one-dimensional anharmonic lattices. PMID- 9975532 TI - Lattice dynamics of SiC polytypes within the bond-charge model. PMID- 9975533 TI - Nonuniversal diffusivity exponent for the soft-percolation process in two dimensions. PMID- 9975535 TI - Quantum theory of the strong magneto-optical effect of Ce-substituted yttrium iron garnet. PMID- 9975534 TI - Magnetic and pairing correlations in coupled Hubbard planes. PMID- 9975536 TI - Nonlinear self-localized dipole-exchange surface spin waves on ferromagnetic media. PMID- 9975538 TI - Orbital magnetization of a finite anyon system: A Hartree calculation on a cylinder. PMID- 9975537 TI - Numerical diagonalization study of an S=1/2 ladder model with open boundary conditions. PMID- 9975539 TI - Phase diagram of thin antiferromagnetic films in strong magnetic fields. PMID- 9975540 TI - Longitudinal-relaxation effects on transverse magnetization and the nuclear magnetic-resonance line shape. PMID- 9975541 TI - Crossover from in-plane to perpendicular magnetization in ultrathin Ni/Cu(001) films. PMID- 9975542 TI - Magnetostatic surface and guided modes of lateral-magnetic-superlattice films. PMID- 9975543 TI - Spin-flip scattering of low-energy electrons from magnetic surfaces near their ordering temperature: Application to Cr(110). PMID- 9975544 TI - Pressure dependence of the magnetic order in RMn2 (R=rare earth). PMID- 9975545 TI - Oscillatory interlayer exchange coupling in Co/Ru multilayers and bilayers. PMID- 9975546 TI - Thermodynamics and spin gap of the Heisenberg ladder calculated by the look-ahead Lanczos algorithm. PMID- 9975547 TI - Scaling theory for the quantum spin-glass transition. PMID- 9975548 TI - Hyperuniversality of a fully anisotropic three-dimensional Ising model. PMID- 9975549 TI - Effects of randomness at interfaces on the exchange coupling in magnetic multilayers. PMID- 9975550 TI - Surface impedance of a type-II superconductor in dc magnetic fields parallel and tilted to the superconductor border. PMID- 9975551 TI - Cancellation of quasiparticle mass enhancement in the conductance of point contacts. PMID- 9975552 TI - Anisotropic flux pinning in a network of planar defects. PMID- 9975553 TI - Trial shadow wave function for the ground state of 4He. PMID- 9975554 TI - Exact-diagonalization study of the Hubbard model with nearest-neighbor repulsion. PMID- 9975556 TI - Anomalous vortex diffusion in proximity-junction arrays. PMID- 9975555 TI - Electrodynamics of the organic superconductorsinebreak kappa -(BEDT-TTF)2Cu(NCS)2 and kappa -(BEDT-TTF)2Cu PMID- 9975557 TI - Enhancement of superconductivity and observation of antilocalization in thin metal films by suppression of electron-interaction effects. PMID- 9975558 TI - Effect of competition between point and columnar disorder on the behavior of flux lines in (1+1) dimensions. PMID- 9975559 TI - Kinetic inductance of Josephson-junction arrays: Dynamic and equilibrium calculations. PMID- 9975561 TI - Nuclear-spin-lattice relaxation-rate measurements in YBa2Cu3O7. PMID- 9975560 TI - Unconventional superconducting order parameters without nodes: The density of states and impurity scattering. PMID- 9975562 TI - Chemical doping and intergranular magnetic-field effects in bulk thallium-based superconductors. PMID- 9975563 TI - Magnetic screening in proximity-coupled superconductor/normal-metal bilayers. PMID- 9975564 TI - Initial-vortex-entry-related magnetic hysteresis in thin-film SQUID magnetometers. PMID- 9975565 TI - Effects of hole doping and electron-phonon interaction on the electronic structure of Ba1-xKxBiO3 studied by photoemission spectroscopy. PMID- 9975566 TI - High-frequency random telegraph voltage noise in high-Tc thin films. PMID- 9975567 TI - Angular scaling of the microwave magnetodissipation in Bi2Sr2CaCu2O8+x. PMID- 9975568 TI - Charge-transfer and barrier-layer effects in YBa2Cu3O7 superlattices. PMID- 9975570 TI - Effect of oxygen stoichiometry in CuO. PMID- 9975569 TI - Normal modes and specific heat of a lattice of undamped pancake vortices in thin superconducting mulitlayers. PMID- 9975571 TI - Dynamic phenomena in superconducting oxides measured by ESR. PMID- 9975572 TI - Anisotropic flux dynamics in single-crystalline and melt-textured YBa2Cu3O7- delta. PMID- 9975573 TI - Magnetic properties of slablike Josephson-junction arrays. PMID- 9975574 TI - Dopant interactions in superconducting YBa2Cu3O7. PMID- 9975575 TI - Abrikosov flux lattice in planar crystals of YBa2Cu3O7- delta. PMID- 9975576 TI - Resistive behavior of high-Tc superconductors with a logarithmiclike pinning potential. PMID- 9975578 TI - Range of the t-J model parameters for CuO2 planes: Experimental data constraints. PMID- 9975577 TI - Observation of the effects of phonon dispersion on the Frohlich-interaction induced second-order Raman scattering in Pb2Sr2PrCu3O8. PMID- 9975579 TI - Volume dependence of the superconducting transition temperature for the high temperature superconductor HgBa2Ca2-xPbxCu3O8+ delta. PMID- 9975580 TI - Ballistic-electron emission into vacuum from a scanning-tunneling-microscope tip through free-standing gold films. PMID- 9975581 TI - High-pressure study of Fe3O4 through the Verwey transition. PMID- 9975582 TI - Elastic moduli of the Laves-phase pseudobinary compounds Zr(AlxFe1-x)2 as determined by ultrasonic measurements. PMID- 9975584 TI - Average Gibbs energy per lattice defect. PMID- 9975583 TI - Autler-Townes modulation of coherent transients in photoexcited color centers. PMID- 9975585 TI - Generating functional for a nonequilibrium system coupled to two reservoirs. PMID- 9975586 TI - Angular dependence of circular magnetic x-ray dichroism in rare-earth compounds. PMID- 9975587 TI - Parametric excitation of nonlinear waves in a one-dimensional system of interacting magnons. PMID- 9975588 TI - Origin of magnetic dichroism in angular-resolved photoemission from ferromagnets. PMID- 9975589 TI - Unrestricted Hartree-Fock upper bounds for the total energy of the Hubbard model on a Bethe lattice of infinite connectivity. PMID- 9975591 TI - Nuclear relaxation rate in layered superconductors with unconventional pairing. PMID- 9975590 TI - Quantum phase transition in the frustrated Heisenberg antiferromagnet. PMID- 9975592 TI - Phase roughening transition in Josephson-junction ladders in random magnetic fields. PMID- 9975593 TI - Transverse ac susceptibility of strips and disks with complex linear resistivity. PMID- 9975594 TI - Phase shift, the Marshall sign, and the Luttinger-liquid behavior in one dimension. PMID- 9975596 TI - Vibrating-reed studies of flux penetration in YBa2Cu3O7- delta. PMID- 9975595 TI - High-pressure Raman study of the coupling of crystal-field excitations to phonons in Nd-containing cuprates. PMID- 9975597 TI - Size limitation of vortex fluctuations in transport-current-carrying Bi2Sr2Ca2Cu3O10 high-temperature superconductors with preferential grain orientation. PMID- 9975598 TI - Thermally assisted flux-flow approach to the irreversibility line. PMID- 9975599 TI - Critical behavior and the Harris criterion for the random Potts model on hierarchical lattices. PMID- 9975600 TI - Raman scattering in diamond at high pressure: Isotopic effects. PMID- 9975601 TI - Crystal-field effects in PrCu2Si2: An evaluation of evidence for heavy-fermion behavior. PMID- 9975603 TI - Brownian motion and magnetism. PMID- 9975602 TI - Effect of impurities on the low-temperature nonlinear spin-density-wave transport. PMID- 9975604 TI - Bloch oscillation and topological quantization. PMID- 9975605 TI - Superconductivity in the ternary nickel silicide Lu2Ni3Si5. PMID- 9975606 TI - Structure of a vortex line in a dx2-y2 superconductor. PMID- 9975607 TI - Upper critical field in a spin-charge-separated superconductor. PMID- 9975609 TI - Precision measurement of the in-plane penetration depth lambda ab(T) in YBa2Cu3O7 delta using grain-boundary Josephson junctions. PMID- 9975608 TI - Critical magnetic fields of superconducting Ba6C60. PMID- 9975610 TI - Dynamically assisted interlayer hopping in YBa2Cu3O6+x. PMID- 9975612 TI - Metal-insulator transitions and dilute electron and hole doping in the extended Hubbard (d-p) model. PMID- 9975611 TI - Transport in polyaniline networks near the percolation threshold. PMID- 9975613 TI - Path-length distribution of electrons reflected elastically from solids. PMID- 9975615 TI - Ionic-covalent transition in titanium oxides. PMID- 9975614 TI - Two-phase coexistence and semimetallic states in conducting polymers. PMID- 9975616 TI - Back-flow electric current: dc current as a quadratic response to an ac field. PMID- 9975617 TI - Chebyshev expansions for the scattering matrices in full-potential Korringa-Kohn Rostoker band-structure calculations. PMID- 9975618 TI - Theory of magnetotransport in a composite medium with periodic microstructure for arbitrary magnetic fields. PMID- 9975620 TI - Pseudoparticle-operator description of an interacting bosonic gas. PMID- 9975619 TI - Extended Hubbard model at weak coupling. PMID- 9975622 TI - Cyclotron resonance and strong phonon coupling in n-type ZnS at high magnetic fields up to 220 T. PMID- 9975621 TI - Low-energy properties of fermions with singular interactions. PMID- 9975623 TI - Exciton magnetic polarons in the semimagnetic alloys Cd1-x-yMnxMgyTe. PMID- 9975624 TI - Bose condensation and superfluidity of excitons in a high magnetic field. PMID- 9975625 TI - Structural study of crystallization of a-Ge using extended x-ray-absorption fine structure. PMID- 9975626 TI - Positron-lifetime measurements between 300 and 800 K in GaAs and GaP. PMID- 9975628 TI - Temperature dependence of the EL2 metastability in semi-insulating GaAs: Thermal hysteresis between the metastable and reverse transitions. PMID- 9975627 TI - Stimulated Brillouin scattering of electromagnetic waves in magnetized semiconductor plasmas. PMID- 9975629 TI - Raman-scattering spectra of coupled LO-phonon-hole-plasmon modes in p-type GaAs. PMID- 9975630 TI - Lattice-constant dependence of the dynamical effective charge in AlAs and GaAs. PMID- 9975631 TI - Composition-dependent energy spectrum of electrons in Hg1-xFexSe solid solution. PMID- 9975632 TI - Structure of amorphous semiconductors: Reverse Monte Carlo studies on a-C, a-Si, and a-Ge. PMID- 9975634 TI - X-ray photoelectron spectroscopy and theory of the valence band and semicore Ga 3d states in GaN. PMID- 9975633 TI - Magnetic properties of Cr-based diluted magnetic semiconductors. PMID- 9975635 TI - Raman studies of intrasubband plasmons in laterally modulated two-dimensional electron gases. PMID- 9975636 TI - Intermittent breakdown of current-oscillation tori in n-type GaAs epitaxial layers. PMID- 9975637 TI - Ultrafast nonlinearities in semiconductor laser amplifiers. PMID- 9975638 TI - Theoretical study of the anharmonic decay of nonequilibrium LO phonons in semiconductor structures. PMID- 9975639 TI - Symmetry breaking in pseudomorphic V-groove quantum wires. PMID- 9975640 TI - Crossover from single-level to multilevel transport in artificial atoms. PMID- 9975641 TI - Electronic transport in metallic iron disilicide. PMID- 9975642 TI - Effects of an impurity on the conductance and thermopower of a saddle-point potential quantum point contact. PMID- 9975643 TI - First-principles calculations of band-edge electronic states of silicon quantum wires. PMID- 9975644 TI - Intensity dependence of the photoreflectance amplitude in semiconductors. PMID- 9975646 TI - Exchange interaction of excitons in GaAs heterostructures. PMID- 9975645 TI - Photoelectron core-level spectroscopy and scanning-tunneling-microscopy study of the sulfur-treated GaAs(100) surface. PMID- 9975647 TI - Ab initio study of cesium chemisorption on the GaAs(110) surface. PMID- 9975648 TI - Electronic structure of GaF3 films grown on GaAs via exposure to XeF2. PMID- 9975649 TI - Surface core-level shifts of Si(111)7 x 7: A fundamental reassessment. PMID- 9975650 TI - Quantum wells with corrugated interfaces: Theory of electron states. PMID- 9975651 TI - Characterization of Si/Si1-xGex/Si quantum wells by space-charge spectroscopy. PMID- 9975652 TI - Exciton-phonon interaction in CdSe and CuCl polar semiconductor nanospheres. PMID- 9975653 TI - Carrier thermalization in sub-three-dimensional electronic systems: Fundamental limits on modulation bandwidth in semiconductor lasers. PMID- 9975654 TI - Atomic rearrangement at ZnTe/CdSe interfaces. PMID- 9975655 TI - Epitaxial continued-layer structure of Sb on GaAs(110) as observed by grazing incidence x-ray diffraction. PMID- 9975656 TI - Epitaxial growth mechanisms and structure of CaF2/Si(111). PMID- 9975657 TI - Vibrational modes on Si(111)1 x 1-As studied by electron-energy-loss spectroscopy. PMID- 9975659 TI - Topological defects, orientational order, and depinning of the electron solid in a random potential. PMID- 9975658 TI - Absence of localization and large dc conductance in random superlattices with correlated disorder. PMID- 9975660 TI - Exciton properties and optical response in InxGa1-xAs/GaAs strained quantum wells. PMID- 9975662 TI - Confinement, surface, and chemisorption effects on the optical properties of Si quantum wires. PMID- 9975661 TI - Bloch oscillations of excitonic wave packets in semiconductor superlattices. PMID- 9975663 TI - Electronic structure and optical properties of PMID- 9975664 TI - Calculations of second-order nonlinear optical susceptibilities in III-V and II VI semiconductor heterostructures. PMID- 9975665 TI - Correlated-interfacial-roughness anisotropy in Si1-xGex/Si superlattices. PMID- 9975666 TI - Surface electronic structure of Tm(0001) and Yb(111). PMID- 9975667 TI - Inner-shell promotions in low-energy Li+-Al collisions at clean and alkali covered Al(100) surfaces. PMID- 9975668 TI - Importance of confined fields in near-field optical imaging of subwavelength objects. PMID- 9975669 TI - Electronic structure of ultrathin Fe films on TiO2(110) studied with soft-x-ray photoelectron spectroscopy and resonant photoemission. PMID- 9975670 TI - Surface core-level shifts and atomic coordination at a stepped W(110) surface. PMID- 9975671 TI - Theory of strained-layer epitaxial growth near step flow. PMID- 9975672 TI - Effect of defects on the stability of heteroepitaxial ceramic interfaces studied by computer simulation. PMID- 9975674 TI - Local structure of c(2 x 2)-Na on Al(001): Experimental evidence for the coexistence of intermixing and on-surface adsorption. PMID- 9975673 TI - Picosecond ultrasonic study of localized phonon surface modes in Al/Ag superlattices. PMID- 9975676 TI - Interface hybridization and spectral distribution in strongly correlated itinerant magnetic systems. PMID- 9975675 TI - Statistical treatment of dynamical electron diffraction from growing surfaces. PMID- 9975677 TI - Relation between the surface impedance and the extinction theorem on a rough surface. PMID- 9975679 TI - Energy dependence of the Nernst-Ettingshausen effect induced by pulsed laser light in bismuth films. PMID- 9975678 TI - 1.681-eV luminescence center in chemical-vapor-deposited homoepitaxial diamond films. PMID- 9975680 TI - Electron-stimulated desorption of positive ions from physisorbed monolayers of H2, HD, and D2 on graphite and D2 on Kr-plated graphite. PMID- 9975682 TI - Stabilized jellium model for the average electron density. PMID- 9975681 TI - Electron-stimulated desorption total-removal cross sections for H2 and HD monolayers physisorbed on graphite. PMID- 9975684 TI - Ab initio calculation of thermodynamic properties of silicon. PMID- 9975683 TI - Concise calculations of the ground-state energy for the strongly bound exciton phonon system. PMID- 9975685 TI - Model of magnetic and chemical disorder in dilute magnetic semiconductors. PMID- 9975687 TI - Derivation of an asymptotic expression in Beenakker's general fluctuation formula for random-matrix correlations near an edge. PMID- 9975686 TI - Excitons in a spatiotemporal lattice. PMID- 9975688 TI - Electron density in AlxGa1-xAs/GaAs-based two-dimensional systems in the quantum Hall regime. PMID- 9975689 TI - Bulk and surface phonon polaritons in three-layer superlattices. PMID- 9975690 TI - Current scaling in the integer quantum Hall effect. PMID- 9975691 TI - Bulk and surface densities of states of 0.3- microm-thick hydrogenated amorphous silicon films using photothermal deflection spectroscopy. PMID- 9975692 TI - Focusing and defocusing in electron scattering along atomic chains. PMID- 9975693 TI - Studies on H-terminated Si(100) surfaces by second-harmonic generation. PMID- 9975695 TI - Photoacoustic characterization of the thermal properties of a semiconductor-glass two-layer system. PMID- 9975694 TI - Adsorption mechanism and kinetics of chlorine on Si(100)-2 x 1: A theoretical study. PMID- 9975696 TI - Scanning-tunneling-microscopy images of Ge adsorbed on an As-covered Si(001) surface. PMID- 9975698 TI - Negative differential conductance in quantum waveguides. PMID- 9975697 TI - Pressure-induced conduction-band crossover in a ZnSe/ZnS0.18Se0.82 symmetric superlattice. PMID- 9975699 TI - Conduction anisotropy in layered semiconductors. PMID- 9975700 TI - Nonvariational approach to impurity states in quantum wires. PMID- 9975701 TI - Exciton dynamics in disordered quantum wells: Localized and delocalized regimes. PMID- 9975702 TI - Localized excitons in cubic Zn1-xCdxS lattice matched to GaAs. PMID- 9975703 TI - Approaches to the tunneling time based on the Larmor clock and absorption probabilities as particular cases of the stay-time method. PMID- 9975704 TI - Time-resolved vacuum Rabi oscillations in a semiconductor quantum microcavity. PMID- 9975705 TI - Effect of the structural anisotropy and lateral strain on the surface phonons of monolayer xenon on Cu(110). PMID- 9975707 TI - Interaction between neutral sodium clusters: Short-range behavior. PMID- 9975706 TI - Spin-resolved photoemission from Pt/Fe(001). PMID- 9975708 TI - Lennard-Jones-potential calculation of C60 stage-one graphite. PMID- 9975709 TI - Localization in the interacting-random-dimer model. PMID- 9975710 TI - Stationary nature of the density-functional free energy: Application to accelerated multiple-scattering calculations. PMID- 9975711 TI - Influence of pseudocore valence-band hybridization on the crystal-structure phase stabilities of transition metals under extreme compressions. PMID- 9975712 TI - Tight-binding total-energy method for transition and noble metals. PMID- 9975713 TI - Magnetic energy bands of carbon nanotubes. PMID- 9975714 TI - Excitons in poly(para-phenylenevinylene). PMID- 9975716 TI - Defect-defect hole transfer and the identity of border traps in SiO2 films. PMID- 9975715 TI - Effect of pressure on defect-related emission in heavily silicon-doped GaAs. PMID- 9975717 TI - Direct mapping of the CoSi2/Si(111) interface by ballistic-electron-emission microscopy and modulation spectroscopy. PMID- 9975718 TI - Time-resolved Raman-spectroscopic evidence for efficient electron trapping in a photodarkened CdSxSe1-x-doped glass: Photocontrol of electrons in semiconductor microcrystallites. PMID- 9975719 TI - Current-density-functional theory of quantum dots in a magnetic field. PMID- 9975720 TI - Magnetoresistance of a two-dimensional electron gas in a random magnetic field. PMID- 9975721 TI - Evidence of biexcitonic contributions to four-wave mixing in GaAs quantum wells. PMID- 9975723 TI - Thin-foil surface-plasmon modification in scanning-probe microscopy. PMID- 9975722 TI - Cyclotron resonance line shape in a Wigner crystal. PMID- 9975724 TI - Step-facilitated dissociation of small metal clusters: A molecular-dynamics study. PMID- 9975725 TI - Bias-dependent STM images of charge-density waves on TaS2. PMID- 9975726 TI - Erratum: Phonon properties of (311) GaAs/AlAs superlattices PMID- 9975728 TI - Electronic structure, phase stability, equation of state, and pressure-dependent superconducting properties of Zr3Al. PMID- 9975727 TI - Dynamical scaling and decay of correlations for spinodal decomposition at Tc. PMID- 9975729 TI - Combined electron-microscope surface-decoration and helium-atom-scattering study of the layer-by-layer photon-stimulated desorption from NaCl cleavage faces. PMID- 9975730 TI - Experimental observation of static disorder in C60 by diffuse neutron scattering. PMID- 9975731 TI - Phenomenological study of the size effect on phase transitions in ferroelectric particles. PMID- 9975732 TI - Mixed-valence transition in YbInCu4. PMID- 9975733 TI - Application of a rate kinetic model of lyoluminescence on heat-treated samples. PMID- 9975734 TI - High-pressure studies of solid iodine by Raman spectroscopy. PMID- 9975735 TI - Infrared characterization of Ge-doped cultured quartz crystals. PMID- 9975736 TI - Frustration on the triangular lattice and incommensurability. PMID- 9975737 TI - Point-defect computer simulation including angular forces in bcc iron. PMID- 9975739 TI - Atomistic computer simulations of yttrium iron garnet as an approach to studying its defect chemistry: Extrinsic defects. PMID- 9975738 TI - Pressure dependence of the Imma phase of silicon. PMID- 9975740 TI - Influence of the defect structure on the refractive indices of undoped and Mg doped lithium niobate. PMID- 9975741 TI - Phonon properties of KNbO3 and KTaO3 from first-principles calculations. PMID- 9975742 TI - Evolution of helium bubbles in aluminum during heavy-ion irradiation. PMID- 9975743 TI - Channeling study on damage in potassium titanyl phosphate induced by ion irradiation. PMID- 9975744 TI - Power law with two parameters for the viscosity of normal and supercooled water. PMID- 9975745 TI - Spatial patterns of sound propagation in sand. PMID- 9975746 TI - Shear modulus of coevaporated Ni1-xZrx thin films. PMID- 9975747 TI - O-D.O deuteron intra- and interbond exchange and frequency-dependent order parameter in deuteron glasses studied by two-dimensional exchange NMR. PMID- 9975748 TI - Phase separation, clustering, and fractal characteristics in glass: A magic-angle spinning NMR spin-lattice relaxation study. PMID- 9975749 TI - Structural properties of amorphous hydrogenated carbon. I. A high-resolution neutron-diffraction study. PMID- 9975750 TI - Structural properties of amorphous hydrogenated carbon. II. An inelastic neutron scattering study. PMID- 9975751 TI - Structural properties of amorphous hydrogenated carbon. III. NMR investigations. PMID- 9975753 TI - Interrelation between the stability of extended normal modes and the existence of intrinsic localized modes in nonlinear lattices with realistic potentials. PMID- 9975752 TI - Dynamics of hydrogen in alpha -LaNi5 hydride investigated by neutron scattering. PMID- 9975754 TI - Classical solitons for a one-dimensional many-body system with inverse-square interaction. PMID- 9975755 TI - Dynamics of a Vicsek fractal: The boundary effect and the interplay among the local symmetry, the self-similarity, and the structure of the fractal. PMID- 9975756 TI - Photoinduced neutral solitons up to room temperature in soluble trans polyacetylene. PMID- 9975758 TI - Quantized Hall conductance and its sign reversal in field-induced spin-density waves. PMID- 9975757 TI - Investigation of anharmonic lattice vibrations with coherent phonon polaritons. PMID- 9975759 TI - Role of excited states in the low-temperature dynamics of tunneling centers in metals: The orbital Kondo effect. PMID- 9975760 TI - Ferromagnetism in FeCu metastable alloys. PMID- 9975761 TI - Contributions to zero-field splitting from spin triplets of 3d4 and 3d6 ions in tetragonal symmetry. PMID- 9975762 TI - Renormalization-group study of the coupled XY-Ising models. PMID- 9975763 TI - Combined effect of hybridization and exchange Coulomb interaction on magnetic ordering in correlated-f-electron cerium systems. PMID- 9975764 TI - Neutron-diffraction study of the magnetic ordering in the insulating regime of the perovskites RNiO3 (R=Pr and Nd). PMID- 9975766 TI - Theory of nonlinear surface spin waves. PMID- 9975765 TI - Magnetic anisotropy of transition-metal thin films: Convergence properties. PMID- 9975767 TI - Path-integral approach to the quasiclassical theory for giant magnetoresistance in magnetic multilayers. PMID- 9975768 TI - Decoupling of the spin-wave and the spin-flip contributions for the anisotropic Heisenberg systems: A way to interpret the experimental data on the La2CuO4-type magnetics. PMID- 9975769 TI - Optical and magneto-optical properties of PrSb. PMID- 9975770 TI - Lagrangian treatment of magnetic dielectrics. PMID- 9975771 TI - Structural effects on the magnetism of small vanadium clusters. PMID- 9975773 TI - Autocorrelation times for the N-fold-way Monte Carlo algorithm. PMID- 9975772 TI - Microscopic calculations of the finite-size spectrum in the Kondo problem. PMID- 9975774 TI - 19-vertex version of the fully frustrated XY model. PMID- 9975775 TI - Neutron-scattering cross section of the S=1/2 Heisenberg triangular antiferromagnet. PMID- 9975776 TI - Linear and nonlinear ac susceptibility of the canted-spin system: Ce(Fe0.96Al0.04)2. PMID- 9975778 TI - Exact ground state of an open S=1/2 long-range Heisenberg antiferromagnetic spin chain. PMID- 9975777 TI - From the Hubbard model to classical spin-fluctuation theory. PMID- 9975779 TI - Influence of the 3D-2D crossover on the critical current of Nb/Cu multilayers. PMID- 9975781 TI - Theory of the decay luminescence spectrum of a Bose-condensed interacting exciton gas. PMID- 9975780 TI - Investigation of the influence of a magnetic field on the chemical potential of electrons in superconducting and ferromagnetic thin films. PMID- 9975782 TI - Dynamics of vortex liquids in Ginzburg-Landau theories with applications to superconductivity. PMID- 9975783 TI - Binding of electrons to the surface of liquid helium. PMID- 9975784 TI - Nonlinear viscous vortex motion in two-dimensional Josephson-junction arrays. PMID- 9975785 TI - BCS superconductivity with fixed number parity. PMID- 9975786 TI - Phase separation in the s-f model. PMID- 9975787 TI - Raman-active phonons and mode softening in superconducting HgBa2CuO4+ delta. PMID- 9975788 TI - Infrared-active phonons and the superconducting gap of Tc-reduced double-chain YBa2Cu4O8 superconductors. PMID- 9975789 TI - Frequency dependence of the surface impedance of YBa2Cu3O7- delta thin films in a dc magnetic field: Investigation of vortex dynamics. PMID- 9975790 TI - Kohn anomalies in superconductors. PMID- 9975791 TI - High-frequency flux dynamics in single-crystal Nd1.85Ce0.15CuO4. PMID- 9975792 TI - Oxygen-sublattice ordering and intercalation mechanism of chlorine in YBa2Cu3O6+ delta. PMID- 9975793 TI - Substitution of Ga for Cu in RBa2Cu3-xGaxO7-y systems (R=Yb, Er, Y, Dy, Gd, Eu, and Nd). PMID- 9975795 TI - Properties and structure of the F-doped (Bi,Pb)-Sr-Ca-Cu-O superconductor. PMID- 9975794 TI - Two-dimensional and three-dimensional vortex lattice dynamics in DyBa2Cu3O7-(Y1 xPrx)Ba2Cu3O7 coupled heterostructures. PMID- 9975796 TI - Normal-state magnetic susceptibility in TlSr2(Lu1-xCax)Cu2Oy from the underdoped to the overdoped regime. PMID- 9975797 TI - Anomalous peak at low fields in the magnetization versus temperature curve in bulk ceramic high-temperature superconductors. PMID- 9975798 TI - Density of states in unconventional superconductors: Impurity-scattering effects. PMID- 9975799 TI - Anomalous crystal chemistries of the 111In-->111Cd and 181Hf-->181Ta probes in rutile TiO2 studied using perturbed-angular-correlation spectroscopy. PMID- 9975800 TI - Electron-lattice and electron-electron coupling in conjugated polymers: Minimum total-energy calculations on the Hubbard-Peierls Hamiltonian. PMID- 9975801 TI - Critical correlations and susceptibilities in the random-field spherical model. PMID- 9975802 TI - Plaquette expansion of the two-dimensional antiferromagnetic Heisenberg model. PMID- 9975803 TI - Soft longitudinal modes in spin-singlet CuGeO3. PMID- 9975804 TI - Magnetisatization-induced optical second-harmonic generation: A probe for interface magnetism. PMID- 9975805 TI - Numerical simulation of flux-pinning dynamics for a defect in a type-II superconductor. PMID- 9975806 TI - NMR study of the 89Y resonance in fluorinated YBa2Cu3Ox. PMID- 9975807 TI - Tunable atomic-scale Josephson effect in dislocated high-Tc superconductors. PMID- 9975808 TI - Phonon localization and martensitic transformation in NixAl1-x alloys. PMID- 9975809 TI - High-temperature phase diagram of the fullerene C60. PMID- 9975811 TI - Coherence effects in the low-temperature Hall coefficient of the heavy-fermion system UPd2Al3. PMID- 9975810 TI - Small-angle scattering by fractal aggregates: A numerical investigation of the crossover between the fractal regime and the Porod regime. PMID- 9975812 TI - Kagome Heisenberg antiferromagnet: Elementary excitations and low-temperature specific heat. PMID- 9975813 TI - Magnetic circular dichroism in 4f photoemission from terbium. PMID- 9975814 TI - Thermodynamics of the fully frustrated quantum Josephson-junction array: A hybrid Monte Carlo study. PMID- 9975815 TI - Tunneling through a superconducting double barrier and the resonant suppression of Andreev reflection. PMID- 9975816 TI - Effects of transport current and columnar defects on the rf penetration depth of NbSe2. PMID- 9975817 TI - Gap anisotropy in Bi2Sr2CaCu2O8+ delta by ultrahigh-resolution angle-resolved photoemission. PMID- 9975818 TI - Deformation superstructures, tweed, and oxygen-vacancy ordering associated with phase transformations in YBa2Cu3Oz. PMID- 9975819 TI - Competition between polarons and bipolarons in nondegenerate conjugated polymers. PMID- 9975821 TI - Electron correlation in extended systems: Fourth-order many-body perturbation theory and density-functional methods applied to an infinite chain of hydrogen atoms. PMID- 9975820 TI - Selective deexcitation of the 4d94fn+1 excited states studied by resonant photoemission in LaCl3 and CeCl3. PMID- 9975822 TI - Interpretive crystal-field parameters: Application to Nd3+ in GdVO4 and YVO4. PMID- 9975823 TI - Stress tuning of the magnetic properties of a near-metallic sample of silicon doped with phosphorus. PMID- 9975824 TI - Exact exchange-potential band-structure calculations by the LMTO-ASA method: MgO and CaO. PMID- 9975825 TI - Electron spin resonance of Nd3+ and Yb3+ in CdFe4P12. PMID- 9975826 TI - Relativistic photoemission theory for space-filling potentials. PMID- 9975827 TI - Static dielectric response of the electron gas. PMID- 9975829 TI - TiTe2: Inconsistency between transport properties and photoemission results. PMID- 9975828 TI - Electronic structure and valence-band spectra of FeBO3. PMID- 9975830 TI - Embedded-quantum-cluster study of local relaxations and optical properties of Cr3+ in MgO. PMID- 9975831 TI - Electronic states of photocarriers in porous silicon studied by photomodulated infrared spectroscopy. PMID- 9975832 TI - Ab initio calculation of the electronic, structural, and dynamical properties of Zn-based semiconductors. PMID- 9975833 TI - Observation of crossover from three- to two-dimensional variable-range hopping in template-synthesized polypyrrole and polyaniline. PMID- 9975834 TI - Diffusion-melting correlations and the compensation effect in atomic diffusion in Si and Ge. PMID- 9975835 TI - Deep defects in narrow-gap semiconductors. PMID- 9975836 TI - Enhanced carrier photogeneration by defects in conjugated polymers and its mechanism. PMID- 9975838 TI - Discriminative temperature dependencies of differential light-scattering cross sections from an electron gas in semiconductors with a nonparabolic dispersion of energy bands. PMID- 9975837 TI - Theoretical possibility of stage corrugation in Si and Ge analogs of graphite. PMID- 9975839 TI - Low-temperature magnetic, thermal, and transport properties of FeSi. PMID- 9975841 TI - All-electron local-density and generalized-gradient calculations of the structural properties of semiconductors. PMID- 9975840 TI - Effect of ordering on the energy spectrum of narrow-gap III-V alloys: Possibility of the transition into the gapless state. PMID- 9975843 TI - Optical third-harmonic studies of the dispersion in chi -bar(3) for gallium nitride thin films on sapphire. PMID- 9975842 TI - Ideal crystal stability and pressure-induced phase transition in silicon. PMID- 9975844 TI - Surface reconstructions of InSb(100) observed by scanning tunneling microscopy. PMID- 9975845 TI - Structure of a Si(100)2 x 2-Ga surface. PMID- 9975847 TI - Thermoelectric properties of a very-low-mobility two-dimensional electron gas. PMID- 9975846 TI - Coulomb blockade of the Aharonov-Bohm effect in GaAs/AlxGa1-xAs quantum dots. PMID- 9975848 TI - Mechanisms of the adsorption of oxygen molecules and the subsequent oxidation of the reconstructed dimers on Si(001) surfaces. PMID- 9975849 TI - Transport properties of a 1D-1D'-1D quantum system. PMID- 9975850 TI - Model for the emission of Si+ ions during oxygen bombardment of Si(100) surfaces. PMID- 9975851 TI - Bond-length relaxation in Si1-xGex alloys. PMID- 9975852 TI - Electronic structure of free-standing (ZnSe)m(ZnS)n (001) strained-layer superlattices. PMID- 9975853 TI - Spectrally resolved four-wave mixing in semiconductors: Influence of inhomogeneous broadening. PMID- 9975854 TI - Raman modes of the GeS-type orthorhombic phase of PbTe. PMID- 9975855 TI - Renormalization effects in the dense electron-hole magnetoplasma of a strained InxGa1-xAs/GaAs single quantum well after picosecond excitation. PMID- 9975856 TI - Scattering rates of Wannier states in superlattices in an electric field. PMID- 9975858 TI - Instantaneous contribution in time-resolved four-wave mixing from GaAs quantum wells near zero time delay. PMID- 9975857 TI - Hole energy levels and intersubband absorption in modulation-doped Si/Si1-xGex multiple quantum wells. PMID- 9975859 TI - Nonlinear carrier-plasmon interaction in a one-dimensional quantum plasma. PMID- 9975860 TI - Thermodynamics of biexcitons in a GaAs quantum well. PMID- 9975861 TI - Pressure- and laser-tuned Raman scattering in II-VI semiconductor nanocrystals: Electron-phonon coupling. PMID- 9975862 TI - Periodic modulation of Coulomb-blockade oscillations in high magnetic fields. PMID- 9975864 TI - Local-interference theory of conductance fluctuations in ballistic metallic point contacts: Combination of near and remote backscattered trajectories. PMID- 9975863 TI - Metal-overlayer-induced charge-transfer effects in thin SiO2-Si structures. PMID- 9975865 TI - Method of obtaining the stable unit-cell shape in the strained superlattice. PMID- 9975867 TI - Interband absorption due to dipole coupling and interference in isolated quantum wire structures. PMID- 9975866 TI - Description of resonant tunneling near threshold. PMID- 9975869 TI - Generalized Laughlin wave functions including the effect of Coulomb interaction. PMID- 9975868 TI - Low- and high-temperature phases of a Pb monolayer on Ge(111) from ab initio molecular dynamics. PMID- 9975870 TI - Random-matrix theory of quantum size effects on nuclear magnetic resonance in metal particles. PMID- 9975871 TI - Modulation-doped quantum-well wires: Elementary excitation spectra. PMID- 9975872 TI - Shallow donor impurities in GaAs/AlxGa1-xAs superlattices in a magnetic field. PMID- 9975873 TI - Type-II band alignment in Si/Si1-xGex quantum wells from photoluminescence line shifts due to optically induced band-bending effects: Experiment and theory. PMID- 9975874 TI - Calculations of the spin dependence of transport and optical properties in wide parabolic quantum wells. PMID- 9975875 TI - Low-temperature dynamical simulation of spin-boson systems. PMID- 9975876 TI - Density-functional calculation for quasi-two-dimensional hole gases. PMID- 9975877 TI - Density-functional calculation of Landau levels for quasi-two-dimensional hole gases. PMID- 9975878 TI - Density-functional calculations for grain boundaries in aluminum. PMID- 9975879 TI - Scattering of a surface plasmon polariton by a surface defect. PMID- 9975880 TI - Delocalization of the Fe 3d levels in the quasi-two-dimensional correlated insulator FePS3. PMID- 9975882 TI - Temperature variation of the time of inelastic electron relaxation in disordered bismuth films. PMID- 9975881 TI - Structure and growth of butane films adsorbed on graphite. PMID- 9975883 TI - Two-dimensional silicide 5 x 3 structure on Cu(001) as seen by scanning tunneling microscopy and helium-atom scattering. PMID- 9975885 TI - Ag/Fe(001) interface. PMID- 9975884 TI - Deposition, diffusion, and aggregation of atoms on surfaces: A model for nanostructure growth. PMID- 9975886 TI - Femtosecond-tunable measurement of electron thermalization in gold. PMID- 9975888 TI - Scattering of electromagnetic waves from a bounded medium with a random surface. PMID- 9975887 TI - Band-theory calculation of image states on a metal surface. PMID- 9975889 TI - Ab initio studies of hydrocarbon adsorption on stepped diamond surfaces. PMID- 9975890 TI - Improved mean-field scheme for the Hubbard model. PMID- 9975891 TI - Integrable multiparametric impurity model. PMID- 9975892 TI - Transport properties of a one-dimensional two-component quantum liquid with hyperbolic interactions. PMID- 9975893 TI - Validity of the semiclassical interpretation of resonant magnetotunneling spectroscopy experiments. PMID- 9975894 TI - Electronic structure of three-dimensional quantum dots in tilted magnetic fields. PMID- 9975895 TI - Characterization of effective masses in strained quantum-well laser structures. PMID- 9975896 TI - Magnetic field dependence of two-dimensional static shielding in the hydrodynamic model. PMID- 9975897 TI - Bogoliubov theory of Coulomb-coupled PMID- 9975898 TI - Dipole spectra of holes in quantum dots. PMID- 9975899 TI - Effect of band mixing on hole transport along the axis of a semiconductor superlattice. PMID- 9975900 TI - Resonant transport in coupled quantum wells: A probe for scattering mechanisms. PMID- 9975901 TI - Critical size for a metal-nonmetal transition in transition-metal clusters. PMID- 9975902 TI - Molecular structure of a crystal phase coexisting with kappa -(BEDT-TTF)2Cu(NCS)2 studied by scanning tunneling microscopy. PMID- 9975904 TI - Characterization of self-affinity in the global regime. PMID- 9975903 TI - Magic numbers of silicon clusters. PMID- 9975905 TI - Charge-induced vibrational shifts and vibronic coupling constant in charged C60n- PMID- 9975906 TI - Comment on "Metastable length states of a random system: TaS3" PMID- 9975907 TI - Parabolic valence-band dispersion in GaAs for optical interband transitions. PMID- 9975909 TI - Current fluctuation in the Bohm-Aharonov effect. PMID- 9975908 TI - EPR and ENDOR study of the Pb center in porous silicon. PMID- 9975911 TI - Large reduction in hot-carrier energy-loss rates in CdSe caused by nonequilibrium optical phonons. PMID- 9975910 TI - Coherent light emission from condensing polaritons. PMID- 9975912 TI - Tunneling between two-dimensional electron gases in a strong magnetic field. PMID- 9975913 TI - Dimer-row correlations on a Si(001) surface with double-atomic-height steps. PMID- 9975914 TI - High-resolution electron microscopy and inelastic light scattering of purified multishelled carbon nanotubes. PMID- 9975915 TI - Multiple-scattering effects in x-ray-absorption fine structure: Chromium in a tetrahedral configuration. PMID- 9975916 TI - Site determination of radioactive atoms from the interference effect of electron capture x rays. PMID- 9975917 TI - Spectator and participator Auger transitions by resonant excitation of the Mo 2p3/2 orbital in Li2MoO4, MoO3, and MoS2. PMID- 9975918 TI - Physical properties and structural chemistry of Ce(Ni1-xGax)5 alloys. PMID- 9975919 TI - First-principles study of stability and local order in bcc-based Fe-Cr and Fe-V alloys. PMID- 9975920 TI - Variational charge relaxation in ionic crystals: An efficient treatment of statics and dynamics. PMID- 9975921 TI - Size dependence of the ferroelectric transition of small BaTiO3 particles: Effect of depolarization. PMID- 9975922 TI - EPR and 14N electron-nuclear double-resonance measurements on the ionized nearest neighbor dinitrogen center in diamond. PMID- 9975923 TI - Coexistence of one- and three-dimensional Fermi surfaces and heavy cyclotron mass in the molecular conductor (DMe-DCNQI)2Cu. PMID- 9975924 TI - Pulsed-NMR study of the long-range order in solid H2 and D2. PMID- 9975925 TI - Ab initio calculation of the structural and electronic properties of carbon and boron nitride using ultrasoft pseudopotentials. PMID- 9975926 TI - NMR spectra of pure 13C diamond. PMID- 9975927 TI - Dynamics of two-level systems in glasses. PMID- 9975928 TI - Occupancy of central sites in the Zn49Mg32 quasicrystal from total-energy computations on its crystal approximant. PMID- 9975929 TI - Strong-fluctuation theory for a mean electromagnetic field in a statistically homogeneous random medium with arbitrary anisotropy of electrical and statistical properties. PMID- 9975930 TI - Phason strain in an energetic growth model of a quasicrystal. PMID- 9975931 TI - NMR and NQR study of the electronic and structural properties of Al-Cu-Fe and Al Cu-Ru quasicrystals. PMID- 9975932 TI - Inelastic-neutron-scattering studies of poly(p-phenylene vinylene). PMID- 9975933 TI - Governing equations for the coupled electromagnetics and acoustics of porous media. PMID- 9975935 TI - Persistent and transient spectral hole burning in Pr3+- and Eu3+-doped silicate glasses. PMID- 9975934 TI - Disorder in the commensurate intergrowth compound C1TET-TTF(AuI2)0.8. PMID- 9975937 TI - Electrical response of heterogeneous systems and Debye's problem. PMID- 9975936 TI - Electrical response of heterogeneous systems containing inclusions with permanent multipoles. PMID- 9975938 TI - Local-mode dynamics in YH2 and YD2 by isotope-dilution neutron spectroscopy. PMID- 9975940 TI - Computer simulation of the domain dynamics of a quenched system with a large number of nonconserved order parameters: The grain-growth kinetics. PMID- 9975939 TI - Optimal control of laser-generated acoustic waves in solids. PMID- 9975941 TI - Interplay of disorder and anharmonicity in heat conduction: Molecular-dynamics study. PMID- 9975942 TI - Cross relaxation and atomic motion in LiNbO2. PMID- 9975943 TI - Overlap length in spin glasses imposed by magnetic field perturbations. PMID- 9975944 TI - Magnetic transition in highly frustrated SrCr8Ga4O19: The archetypal kagome-acute system. PMID- 9975945 TI - Exchange and spin-orbit contributions to spin-polarized LEED rotation curves of magnetic films: Fe/W(001). PMID- 9975946 TI - Mesoscopic noise in disordered FeZr films: Hydrogen clustering and spin-glass effects. PMID- 9975947 TI - Numerical study of a two-dimensional quantum antiferromagnet with random ferromagnetic bonds. PMID- 9975948 TI - Lattice-vibration and spin-fluctuation effects on photoemission from ferromagnetic Ni. PMID- 9975949 TI - Potts model in an asymmetric random field. PMID- 9975950 TI - Neutron-scattering study of the dynamic spin correlations in CsNiCl3 above Neel ordering. PMID- 9975951 TI - Electronic structure, magnetic, and Fermi-surface properties of UPd2Al3. PMID- 9975952 TI - Simulation study of NMR line shapes in a classical nuclear-spin system with two isotopes. PMID- 9975953 TI - Microwave gap enhancement in low-Tc superconducting thin films. PMID- 9975954 TI - Magnetic order induced by hydrogen in superconducting RBa2Cu4O8 (R=Y,Gd) studied by Mossbauer and NQR techniques. PMID- 9975956 TI - Resistivity, Hall effect, Nernst effect, and thermopower in the mixed state of La1.85Sr0.15CuO4. PMID- 9975955 TI - Suppression of superconductivity by two-channel Kondo impurities. PMID- 9975957 TI - Multiple Andreev and elastic interface scattering in superconductor-normal-metal superconductor junctions. PMID- 9975958 TI - Quantum effects in the structural properties of supercritical 4He. PMID- 9975959 TI - Frequency dependence of sound propagation in superfluid-filled porous media. PMID- 9975961 TI - Evidence for Josephson vortices in (BEDT-TTF)2Cu(NCS)2. PMID- 9975960 TI - Superfluid turbulence in a nonuniform rectangular channel. PMID- 9975962 TI - BCS-Bose model of exotic superconductors: Generalized coherence length. PMID- 9975963 TI - Quantum interference on the kagome-acute lattice. PMID- 9975964 TI - Surface tension and kinetic coefficient for the normal/superconducting interface: Numerical results versus asymptotic analysis. PMID- 9975965 TI - Testing models of the symmetry of the superconducting pairing state by low temperature electron irradiation of an untwinned single crystal of YBa2Cu3O7- delta. PMID- 9975966 TI - Eliashberg function of cuprates and fullerides from gap measurements. PMID- 9975967 TI - Magnetization of a superconductor: Results from the critical-state model. PMID- 9975968 TI - Hall effect in the mixed state of superconducting L1.85Ce0.15CuO4 (L=Nd,Sm) single crystals. PMID- 9975969 TI - Multiple peaks in the ac susceptibility of untwinned Y-Ba-Cu-O single crystals: A manifestation of the peak effect. PMID- 9975971 TI - Nearly antiferromagnetic Fermi-liquid description of magnetic scaling and spin gap behavior. PMID- 9975970 TI - Crystal structure of (Cu,C)Ba2Ca3Cu4O11+ delta (Tc=117 K) by neutron-powder diffraction analysis. PMID- 9975973 TI - Transition temperature and irreversibility line of cobalt-doped single-crystal YBa2Cu3O7- delta : The effect of high-pressure oxygen annealing. PMID- 9975972 TI - Effects of local moments on the magnetization of HoBa2Cu3O7. PMID- 9975974 TI - Overdoped metals in the Tl2Ba2CuO6+ delta and TlSr2CaCu2O7- delta systems. PMID- 9975976 TI - Superconducting correlations in Hubbard chains with correlated hopping. PMID- 9975975 TI - 151Eu Mossbauer spectroscopy and x-ray-diffraction studies on the Pb2Ba2EuCu3O8+ delta system. PMID- 9975977 TI - Spin fluctuations in La2-xSrxCuO4: NMR versus inelastic neutron scattering. PMID- 9975979 TI - Itinerant frustrated antiferromagnets: New phases induced by anisotropy or a magnetic field. PMID- 9975978 TI - Nitrogen-related defect in CaO. PMID- 9975980 TI - Quantum-well states and exchange coupling in fcc (111) magnetic multilayers. PMID- 9975981 TI - Structure of sputtered Fe/Si multilayers. PMID- 9975982 TI - Temperature-induced magnetic anisotropies in Co/Cu(1 1 17). PMID- 9975984 TI - Third sound and energetics in 3He-4He mixture films. PMID- 9975983 TI - Neutron scattering in a dx2-y2-wave superconductor. PMID- 9975985 TI - Relation between pseudospin-rotation invariance and a supersolid. PMID- 9975986 TI - Ginzburg-Landau coefficients for high-Tc superconductors with a deformable lattice model. PMID- 9975987 TI - Polaron formation and local magnetic moments in cuprate superconductors. PMID- 9975988 TI - Phase transition in RbC60: Vibrational and electronic properties. PMID- 9975989 TI - Diffusion coefficient for interacting lattice gases. PMID- 9975991 TI - Effective chiral-spin Hamiltonian for odd-numbered coupled Heisenberg chains. PMID- 9975990 TI - Magnetic coupling of interfaces: A surface-Green's-function approach. PMID- 9975993 TI - Competition between pinning and melting in the two-dimensional vortex lattice. PMID- 9975992 TI - Tricritical behavior of the frustrated XY antiferromagnet. PMID- 9975994 TI - Low-frequency noise in the normal state of thin-film high-temperature superconductors. PMID- 9975995 TI - Scaling of the Hall coefficient and resistivity in underdoped and overdoped RBa2Cu3Oy films. PMID- 9975997 TI - Erratum: Line-shape description for Mossbauer conversion-electron and transmission geometries PMID- 9975996 TI - Absence of anomalous copper vibrations in YBa2Cu3O7- delta. PMID- 9975998 TI - Erratum: Binding of electrons to the surface of liquid helium PMID- 9975999 TI - Temperature and concentration dependences of acoustic velocity and damping in Rb1 x(ND4)xD2AsO4 mixed crystals by Brillouin backscattering. PMID- 9976000 TI - Commensurate-incommensurate phase transition in the presence of crystal deformation. PMID- 9976001 TI - Anisotropic gamma -ray resonance scattering from a zinc single crystal and the uncertainty principle. PMID- 9976002 TI - Dynamics in incommensurate phases studied by NMR: Theory and relaxation measurements on 87Rb satellites in Rb2ZnCl4. PMID- 9976003 TI - Disordering and dissolution of gamma ' precipitates under ion irradiation. PMID- 9976004 TI - Symmetry change at the fcc-distorted-fcc phase transition of lanthanides under pressure. PMID- 9976005 TI - Frequency upconversion of orange light into blue light in Pr3+-doped fluoroindate glasses. PMID- 9976006 TI - Electron-paramagnetic-resonance study of rhodium impurity ions in KTiOPO4 single crystals. PMID- 9976008 TI - High-pressure structural study of barium to 90 GPa. PMID- 9976007 TI - Structural phase transformations and the equations of state of calcium chalcogenides at high pressure. PMID- 9976010 TI - Radiative and nonradiative decays of La 4d ionized and excited states. PMID- 9976009 TI - Isotope effects in KH2PO4-type crystals. PMID- 9976011 TI - Dynamics of infrared-to-visible upconversion in Cs3Lu2Br9:1%Er3+ PMID- 9976012 TI - Phase transitions and superconductivity of black phosphorus and phosphorus arsenic alloys at low temperatures and high pressures. PMID- 9976013 TI - Charge effects in the structure of an almost-ionic solid: Molecular-dynamics studies. PMID- 9976014 TI - Metal-semiconductor transition and structural change in (BEDT-TTF)3(ClO4)2. PMID- 9976015 TI - Measurement of the soft polariton in KTa0.93Nb0.07O3 by time-resolved four-wave mixing. PMID- 9976016 TI - Energy-level and line-strength analysis of optical transitions between Stark levels in Nd3+:Y3Al5O12. PMID- 9976017 TI - External field in the Landau theory of a weakly discontinuous phase transition: Pressure effect in the martensitic transitions. PMID- 9976019 TI - Dielectric and electro-optical studies of a ferroelectric copolysiloxane. PMID- 9976018 TI - Thermodynamics of atom-vacancy solid solution from a self-diffusion Arrhenius plot. PMID- 9976020 TI - Static structure factor of dilute solutions of polydisperse fractal aggregates. PMID- 9976022 TI - Small polarons and the electronic properties of Mo2S3. PMID- 9976021 TI - Disorder-induced resonance coupling of waves. PMID- 9976023 TI - Moment-expansion-method calculations of phonon line shapes in argon. PMID- 9976024 TI - Percolative diffusion of a dumbbell interstitial defect on a fcc lattice: Calculation of a percolation threshold with use of a series method. PMID- 9976025 TI - Gamma phonons and microscopic structure of orthorhombic KNbO3 from first principles calculations. PMID- 9976026 TI - Strong Mn-Mn distance dependence of the Mn interlayer coupling in SmMn2Ge2 related compounds and its role in magnetic phase transitions. PMID- 9976027 TI - Soliton-phonon interaction in anharmonic quasi-one-dimensional ferromagnetic crystals: Soliton-induced modification of the speed of sound. PMID- 9976028 TI - Paramagnetic-ferromagnetic phase transition during growth of ultrathin Co/Cu(001) films. PMID- 9976029 TI - 1/N expansion for the Schwinger-boson theory of quantum antiferromagnets. PMID- 9976030 TI - Magnetism in the spin-density-wave alloy Cr1-xMnx (x=0.007). PMID- 9976032 TI - Antiferromagnetic stacked triangular lattices with Heisenberg spins: Phase transition and effect of next-nearest-neighbor interaction. PMID- 9976031 TI - Ground-state properties of the three-dimensional Ising spin glass. PMID- 9976033 TI - Magnetism of carbon clusters. PMID- 9976034 TI - Axial anisotropy of Co2+ in CdS from magnetization-step and high-frequency EPR. PMID- 9976036 TI - Spin configurations of ABX3 antiferromagnets in an external magnetic field. PMID- 9976035 TI - Raman-scattering study of CuGeO3 in the spin-Peierls phase. PMID- 9976038 TI - Statistical mechanics of nonuniform magnetization reversal. PMID- 9976037 TI - Fluctuations and instabilities of ferromagnetic domain-wall pairs in an external magnetic field. PMID- 9976039 TI - Transition from superconductivity to heavy-fermion behavior in U-doped Lu2Fe3Si5. PMID- 9976040 TI - Flux lattice and vortex structure in 2H-NbSe2 in inclined fields. PMID- 9976041 TI - Titanium nuclear magnetic resonance in metallic superconducting lithium titanate and its lithium-substituted derivatives Li1+xTi2-xO4 (0EL2(*) metastable transformation. PMID- 9977822 TI - Dimensionality of exciton-state renormalization in highly excited semiconductors. PMID- 9977821 TI - Evidence for the formation of tellurium-hydrogen complexes in crystalline silicon. PMID- 9977823 TI - Experimental study of tunneling escape through double-barrier resonant-tunneling structures. PMID- 9977824 TI - Quantum transport through a one-dimensional ring with tunnel junctions. PMID- 9977825 TI - Far-infrared absorption in coupled quantum dots. PMID- 9977827 TI - Magnetoresistance of a two-dimensional electron gas in nearly parallel magnetic fields. PMID- 9977826 TI - Dangling-bond adsorption site for potassium on Si(100)-(2 x 1). PMID- 9977828 TI - Exchange energy for electrons in two dimensions: Effects of finite temperature and finite thickness. PMID- 9977829 TI - Josephson phenomena and quantum ferromagnetism in double-layer quantum Hall systems. PMID- 9977830 TI - Observation of extreme field-induced mass deviations in double quantum wells. PMID- 9977832 TI - Photonic gaps in the dispersion of surface plasmons on gratings. PMID- 9977831 TI - Giant field-induced variation of the cyclotron mass in coupled two-dimensional electron gases. PMID- 9977833 TI - Disorder and absorption edges in ion-irradiated hydrogenated amorphous carbon films. PMID- 9977834 TI - Morphological instability caused by asymmetry in step kinetics. PMID- 9977835 TI - Symmetry properties of chiral carbon nanotubes. PMID- 9977836 TI - Comment on "Role of interfacial oxide-related defects in the red-light emission in porous silicon" PMID- 9977837 TI - Reply to "Comment on 'Role of interfacial oxide-related defects in the red-light emission in porous silicon' " PMID- 9977838 TI - Exciton dispersion in a structure of N coupled multiple quantum wells. PMID- 9977839 TI - Ab initio molecular dynamics in adaptive coordinates. PMID- 9977840 TI - Two-peak photoluminescence and light-emitting mechanism of porous silicon. PMID- 9977841 TI - Stability and dynamics of surface vacancies on GaAs(110). PMID- 9977842 TI - Ab initio study of structure and dynamics of the Si(100) surface. PMID- 9977843 TI - Subpicosecond spectroscopy of the optical nonlinearities of CuCl quantum dots. PMID- 9977844 TI - Interface exciton magnetic polaron in ZnSe/Zn1-xMnxSe quantum-well structures. PMID- 9977845 TI - Phase coherence and trajectory trapping around one or two independently controllable antidots in quantum wires. PMID- 9977847 TI - Multistability of conductance in doped semiconductor superlattices. PMID- 9977846 TI - chi (5) signature in the four-wave-mixing signal from a GaAs/Al0.3Ga0.7As superlattice. PMID- 9977848 TI - Determination of mode-cutoff wavelengths and refractive-index profile of planar optical waveguides with a photon scanning tunneling microscope. PMID- 9977850 TI - Convergent real-space cluster expansion for configurational disorder in ionic systems. PMID- 9977849 TI - Synthesis of BxCyNz nanotubules. PMID- 9977851 TI - High-pressure behavior in alpha -AlPO4: Amorphization and the memory-glass effect. PMID- 9977853 TI - Fracture simulations using large-scale molecular dynamics. PMID- 9977852 TI - Defect clustering and self-healing of electron-irradiated boron-rich solids. PMID- 9977855 TI - Using parametric B splines to fit specular reflectivities. PMID- 9977854 TI - Modeling the O2--O2- interaction for atomistic simulations. PMID- 9977856 TI - Phonon anomaly, central peak, and microstructures in Ni2MnGa. PMID- 9977857 TI - NMR study of ammonium magnesium langbeinite. PMID- 9977858 TI - Phase diagram for UPd3 subject to symmetry-breaking stress and magnetic field. PMID- 9977859 TI - X-ray-scattering study of the cubic-to-tetragonal transition and its precursive phenomenon in V3Si. PMID- 9977860 TI - Water diffusion in zeolite 4A beds measured by broad-line magnetic resonance imaging. PMID- 9977861 TI - Lifshitz tail in a model of interacting particles. PMID- 9977862 TI - Nonexponentiality and thermal variation of nuclear relaxation in glasses. PMID- 9977863 TI - Transition between flocculation and percolation of a diffusion-limited cluster cluster aggregation process using three-dimensional Monte Carlo simulation. PMID- 9977864 TI - Electronic structure of decagonal Al65Co15Cu20 and Al70Co15Ni15. PMID- 9977865 TI - Monte Carlo simulation of interface alloying. PMID- 9977866 TI - Resonant nonlinear optical properties and excited-state dynamics of pristine, oxygen-doped, and photopolymerized C60 in the solid state. PMID- 9977867 TI - Quantum mechanics, quantum-classical correspondence, thermodynamics, and response of a small anharmonic periodic chain. PMID- 9977869 TI - Perturbative approach to the dynamics of a linear chain with hierarchical coupling. PMID- 9977868 TI - Intermolecular Raman scattering and electron-energy-loss studies of AxC60. PMID- 9977870 TI - Advances in the effective-potential Monte Carlo method. PMID- 9977871 TI - Enhanced nonlinear response of fractal clusters. PMID- 9977872 TI - Tunneling systems in polycrystalline metals: Absence of electron-assisted relaxation. PMID- 9977873 TI - Femtosecond spectroscopy of electron-electron and electron-phonon energy relaxation in Ag and Au. PMID- 9977874 TI - Strongly correlated spin-phonon systems: A scenario for heavy fermions. PMID- 9977875 TI - Individual-domain-wall motion in Ni0.77Mn0.23 observed via resistance fluctuations. PMID- 9977876 TI - Importance of electronic structure of the M ions for the heavy-fermion behavior in CexM1-xPb3 (M=Y,Th). PMID- 9977877 TI - Magnetic behavior of transition-metal impurities in alkali-earth metals. PMID- 9977879 TI - Nuclear magnetic resonance on oriented nuclei: Resonance shift with the external magnetic field. PMID- 9977878 TI - Double-peak structure of the dynamical structure factor in diluted Heisenberg antiferromagnets. PMID- 9977880 TI - Electronic structure and magnetic properties of LaFeO3 at high pressure. PMID- 9977882 TI - Critical behavior of randomly pinned spin-density waves. PMID- 9977881 TI - Possibility for an intermediate-spin ground state in the charge-transfer material SrCoO3. PMID- 9977883 TI - Theory of electromagnetic modes of a magnetic superlattice in a transverse magnetic field: An effective-medium approach. PMID- 9977884 TI - Aggregation and segregation in a mixture of magnetic and nonmagnetic particles. PMID- 9977885 TI - Enhanced magnetization of nanoscale colloidal cobalt particles. PMID- 9977887 TI - Empty electronic states in magnetic thin films: Fe on Au(100), Ag(100), and Cu(100). PMID- 9977886 TI - Ferrimagnetism in diluted mixed Ising spin systems. PMID- 9977888 TI - Possibility of various magnetic configurations in the Cr (Fe) monolayer deposited on vicinal surfaces of Fe (Cr). PMID- 9977889 TI - Superfluidity of lattice semions. PMID- 9977890 TI - Magnetization and resistivity of UNi4B in high magnetic fields. PMID- 9977891 TI - Spin dynamics of the triangular Heisenberg antiferromagnet: A Schwinger-boson approach. PMID- 9977892 TI - Effective lattice actions for correlated electrons. PMID- 9977893 TI - Orbital magnetization in the hopping regime. PMID- 9977894 TI - Nonplanar spiral states of the t-J model with classical spins. PMID- 9977895 TI - Correlation of impurity potential, s-d scattering, and giant magnetoresistance in magnetic granular alloys. PMID- 9977897 TI - Enhanced magnetism in amorphous Co-Y alloys: An ab initio approach. PMID- 9977896 TI - Spatial periodicity of the spin-1/2 Heisenberg antiferromagnetic chain with competing interactions. PMID- 9977899 TI - Theory of anomalous proximity effects in phase-coherent structures. PMID- 9977898 TI - Strong-coupling limit of Eliashberg theory. PMID- 9977900 TI - Interlayer coupling and the metal-insulator transition in Pr-substituted Bi2Sr2CaCu2O8+y. PMID- 9977901 TI - Heat-capacity studies in the Y5-xDyxOs4Ge10 system. PMID- 9977903 TI - Quasiparticle effective mass in the superconducting phase of heavy-fermion systems. PMID- 9977902 TI - Undulating vortices in layered superconductors. PMID- 9977905 TI - Spin and charge dynamics of the two-dimensional t-J model at intermediate electron densities: Absence of spin-charge separation. PMID- 9977904 TI - Low-angle resistivity anomaly in layered superconductors. PMID- 9977907 TI - Stability of the vortex lattice in a rotating superfluid. PMID- 9977906 TI - Uniform coupling of microwaves to nonlinear resonant modes in Josephson junctions. PMID- 9977908 TI - Optical conductivity of the infinite-dimensional Hubbard model. PMID- 9977909 TI - Crossover from two- to three-dimensional behavior in superfluids. PMID- 9977910 TI - Nonmagnetic impurities in two-dimensional superconductors. PMID- 9977911 TI - Self-consistent microscopic theory of surface superconductivity. PMID- 9977912 TI - Upper critical field in the gauge model. PMID- 9977914 TI - Doping dependence of the Fermi surface in the t-J model. PMID- 9977913 TI - Superconducting micronets: The Wheatstone bridge. PMID- 9977915 TI - Resistivity transitions in applied magnetic fields in epitaxial thin films of Fe- and Zn-doped YBa2Cu3O7- delta. PMID- 9977916 TI - Relationship between pressure-induced charge transfer and the superconducting transition temperature in YBa2Cu3O7- delta superconductors. PMID- 9977917 TI - Equilibrium superconducting properties of grain-aligned HgBa2Ca2Cu3O8+ delta. PMID- 9977918 TI - Charge transfer in high-Tc superconducting superlattices. PMID- 9977920 TI - London penetration depth in a tight-binding model of layered narrow-band anisotropic superconductors. PMID- 9977921 TI - Evidence for d-wave superconductivity in YBa2Cu3O7- delta from far-infrared conductivity. PMID- 9977919 TI - Superconductivity in the Sr-Ca-Cu-O system and the phase with infinite-layer structure. PMID- 9977923 TI - Unusual thickness dependence of the magnetic critical-current density for granular high-Tc films. PMID- 9977922 TI - Relaxation of persistent current and the energy barrier Ueff(J) close to Tc in a grain-aligned YBa2Cu3O7- delta ring. PMID- 9977924 TI - Thermoelectric power and resistivity of La1.8Sr0.2CaCu2O6- delta and the effects of O2 hot-isostatic-press annealing. PMID- 9977925 TI - Role of Ba-site Pr in quenching superconductivity of Y1-yPryBa2Cu3Ox and related materials. PMID- 9977926 TI - Current-voltage measurements of thin YBa2Cu3O6.9 films compared with a modified Ambegaokar-Halperin theory. PMID- 9977927 TI - Evaluation of oxygen isotope experiments on Pr-, Ca-, and Zn-substituted YBa2Cu3O7. PMID- 9977928 TI - Mechanism of charge-spin separation in the t-J model: Dynamics of U(1) gauge theory with multiple gauge fields. PMID- 9977929 TI - Existence of hole pockets in the two-dimensional Hubbard model. PMID- 9977930 TI - Topological defects in the Abrikosov lattice of vortices in type-II superconductors. PMID- 9977931 TI - Thermal boundary resistance and diffusivity for YBa2Cu3O7- delta films. PMID- 9977932 TI - ESR of Gd3+ and Er3+ in Pr2-xCexCuO4. PMID- 9977933 TI - Electronic structure of Bi2Sr2CaCu2O8+ delta and Tl2Ba2CaCu2O8: Near-O-1s threshold excitation x-ray fluorescence studies. PMID- 9977934 TI - Electron-spin-resonance study of the dimer state of KC60 and its transformations. PMID- 9977935 TI - Localized vibrational modes around bipolarons in polythiophene. PMID- 9977936 TI - Nature of the first diffraction peak in glassy selenium. PMID- 9977937 TI - Optical phonon modes in GaN and AlN. PMID- 9977938 TI - Disorder-induced fluctuations in the magnetic properties of an Anderson-Hubbard model. PMID- 9977940 TI - Magnetic properties of spherical fcc clusters with radial surface anisotropy. PMID- 9977939 TI - Evidence of spin-glass ordering in sputtered Y81.9Tb2.6Si15.5 metallic glasses. PMID- 9977941 TI - Flux-lattice melting and depinning in the weakly frustrated two-dimensional XY model. PMID- 9977942 TI - Possibility of reconciliation on the type of the order parameter in high temperature superconductors. PMID- 9977943 TI - pi -vortex state in a long 0- pi Josephson junction. PMID- 9977944 TI - Observation of an electromagnetic absorption peak in the millimeter wave range in liquid helium at the superfluid lambda transition. PMID- 9977945 TI - Instability in the current-biased 0- pi Josephson junction. PMID- 9977947 TI - Numerical investigations on interactions between tangles of quantized vortices and second sound. PMID- 9977946 TI - Vortex renormalization in three space dimensions. PMID- 9977948 TI - Pair breaking by magnetic impurities in ultrathin superconducting films: Tc degradation mechanisms in disordered superconductors. PMID- 9977949 TI - Critical supersaturation of 3He-4He liquid mixtures at low temperatures. PMID- 9977950 TI - Three-dimensional XY scaling of the resistivity of YBa2Cu3O7- delta single crystals. PMID- 9977951 TI - CuO2 bilayer containing magnetic impurities. PMID- 9977952 TI - Paraconductivity along the a and b axes in YBa2Cu3O7- delta single crystals. PMID- 9977953 TI - Disorder effects in the t-J model. PMID- 9977955 TI - Reply to "Comment on 'Correlation functions for ionic motion from NMR relaxation and electrical conductivity in the glassy fast-ion conductor (Li2S)0.56(SiS2)0.44' " PMID- 9977954 TI - Comment on "Correlation functions for ionic motion from NMR relaxation and electrical conductivity in the glassy fast-ion conductor (Li2S)0.56(SiS2)0.44" PMID- 9977956 TI - Critical temperature of two coupled Ising planes. PMID- 9977957 TI - Reply to the Comment "Critical temperature of the two coupled Ising planes" PMID- 9977958 TI - Comment on "Particle-size effects on the value of TC of MnFe2O4: Evidence for finite-size scaling" PMID- 9977959 TI - Comment on "Generalization of the Abragam relaxation function to a longitudinal field" PMID- 9977960 TI - Comment on "Angle dependence of the upper critical field of superconducting superlattices" PMID- 9977961 TI - Room-temperature compressibility of C60: Intercalation effects with He, Ne, and Ar. PMID- 9977962 TI - Conducting phase of rapidly cooled AC60 (A=Cs and Rb). PMID- 9977963 TI - High-pressure phase of copper(I) iodide. PMID- 9977964 TI - Hydrogenation of titanium-based quasicrystals. PMID- 9977965 TI - Absence of a first-order metamagnetic transition in CeRu2Si2. PMID- 9977967 TI - Induced Rh magnetic moments in Fe-Rh and Co-Rh alloys using x-ray magnetic circular dichroism. PMID- 9977966 TI - Spatial distribution of mobile holes in the t-J model. PMID- 9977968 TI - Anomalous flux pinning in a torus of thoriated UBe13. PMID- 9977969 TI - Quasiparticle dispersion of the t-J and Hubbard models. PMID- 9977970 TI - Magnetic-field dependence of the c-axis plasma edge of La1.85Sr0.15CuO4. PMID- 9977971 TI - Additive quasiparticle and vortex Hall conductivities in La2-xSrxCuO4 and untwinned YBa2Cu3O6.93. PMID- 9977973 TI - Erratum: Electron-phonon interaction near Van Hove singularities PMID- 9977972 TI - Distribution of magnetic flux in high-Tc grain-boundary junctions enclosing hexagonal and triangular areas. PMID- 9977974 TI - Erratum: Vortex depinning frequency in YBa2Cu3O7-x superconducting thin films: Anisotropy and temperature dependence PMID- 9977975 TI - Erratum: Ginzburg-Landau theory of fluctuation magnetization of two-dimensional superconductors PMID- 9977976 TI - Nitrogen diffusion and distribution in the Y2Fe17 lattice. PMID- 9977977 TI - In situ high-pressure x-ray-diffraction study of TlReO4 to 14.5 GPa: Pressure induced phase transformations and the equation of state. PMID- 9977978 TI - Model of track formation. PMID- 9977979 TI - Neutron-powder-diffraction study of the long-range order in the octahedral sublattice of LaD2.25. PMID- 9977980 TI - Relaxation effects during the densification of ultrafine powders at high hydrostatic pressure. PMID- 9977981 TI - High-pressure laser spectroscopy of Cr3+:Gd3Sc2Ga3O12 and Cr3+:Gd3Ga5O12. PMID- 9977982 TI - Decomposition of Fe2B by mechanical grinding. PMID- 9977983 TI - High-pressure synthesis, characterization, and equation of state of cubic C-BN solid solutions. PMID- 9977985 TI - EPR evidence of extrinsic symmetry-breaking defects in nominally pure KTaO3. PMID- 9977984 TI - Features of incommensurate phases in K2SeO4, K2ZnCl4, and Rb2ZnCl4. PMID- 9977986 TI - Phase separation in sputtered amorphous metal-germanium alloys. PMID- 9977988 TI - Swift-uranium-ion-induced damage in sapphire. PMID- 9977987 TI - Mossbauer and energy-dispersive x-ray-diffraction studies of the pressure-induced crystallographic phase transition in C-type Yb2O3. PMID- 9977989 TI - Sputtering of LiF films induced by low-energy Ar+ impact. PMID- 9977990 TI - Determination of internal strain by optical measurements. PMID- 9977991 TI - Pressure-induced polymorphism in CuCl: An ab initio study. PMID- 9977992 TI - Diffuse x-ray scattering from thin films with defects. PMID- 9977993 TI - Dimerization in KC60 and RbC60. PMID- 9977994 TI - Molecular-dynamics simulation of hydrogen diffusion in niobium. PMID- 9977995 TI - Theory and computer simulation of diffuse scattering from lattice-gas models: Structure-factor calculations for the high-temperature superconductor YBa2Cu3O6+x. PMID- 9977996 TI - Long-range intensity correlations in wave reflection from a disordered medium. PMID- 9977997 TI - Saxon-Hutner-Luttinger theorem in various physical models in one dimension. PMID- 9977998 TI - Energy master equation: A low-temperature approximation to Bassler's random-walk model. PMID- 9978000 TI - Comparison of neutron-scattering data for tetrahedral amorphous carbon with structural models. PMID- 9977999 TI - Glass-transition dynamics of a polyurethane gel using ultrasonic spectroscopy, dynamic light scattering, and dynamical mechanical thermal analysis. PMID- 9978002 TI - Short-range order in crystalline, amorphous, liquid, and supercooled germanium probed by x-ray-absorption spectroscopy. PMID- 9978001 TI - Quantum interference in liquid metals. PMID- 9978003 TI - Raman scattering study and lattice-dynamics investigation of the NaMnF3 perovskite. PMID- 9978005 TI - Isotopic order by phonon-induced interactions. PMID- 9978004 TI - Soliton excitations in one-dimensional diatomic lattices. PMID- 9978006 TI - Extrapolation to infinite Trotter number in path-integral Monte Carlo simulations of solid-state systems. PMID- 9978008 TI - Numerical studies of chiral ordering in three-dimensional XY spin glasses. PMID- 9978007 TI - Phenomenologial dynamics of C70. PMID- 9978010 TI - Two-dimensional spin-polarized states of Ag on Fe(100). PMID- 9978009 TI - Zero-point spin fluctuations and the magnetovolume effect in itinerant-electron magnetism. PMID- 9978011 TI - Spin excitations in the longitudinally modulated magnetic phase of erbium. PMID- 9978013 TI - Interference of scattering pathways in Raman heterodyne spectroscopy of multilevel atoms. PMID- 9978012 TI - Effect of carbon substitution on the magnetic properties and crystalline phases of melt-spun Nd4Fe77.5B18.5 alloys. PMID- 9978014 TI - Crystal-field excitations and magnetic properties of Ho3+ in HoVO4. PMID- 9978016 TI - Magnetic properties of some equiatomic ternary rare-earth compounds. PMID- 9978015 TI - Finite-temperature phase diagram of the t-J model: Renormalization-group theory. PMID- 9978017 TI - Monte Carlo study of magnetic order at ferromagnetic and antiferromagnetic surfaces: Implications for spin-polarized photoelectron diffraction. PMID- 9978019 TI - Quantum-field-theory approach to the Heisenberg Hamiltonian, modified spin-wave theory, and application to an antiferromagnet with a square lattice. PMID- 9978018 TI - Single-crystal and powder electron-nuclear double resonance of RbCl:O2-: A comparison between the spin Hamiltonian parameters obtained from both experiments. PMID- 9978020 TI - Theory of spin-polarized angle-resolved photoemission spectroscopy of ferromagnetic nickel surfaces. PMID- 9978021 TI - Competing hybridization and consequences for magnetic ordering in ternary and quaternary correlated-electron systems. PMID- 9978022 TI - Magnetic and hyperfine properties of fcc Fe. PMID- 9978023 TI - Static critical behavior of the ferromagnetic Ising model on the quasiperiodic octagonal tiling. PMID- 9978024 TI - Internal friction of dislocations in a magnetic field. PMID- 9978025 TI - Kondo effect in systems of reduced dimensionality. PMID- 9978026 TI - Frustrated bonds and long-range order in quasi-two-dimensional magnets. PMID- 9978027 TI - Perpendicular anisotropy and spin reorientation in epitaxial Fe/Cu3Au(100) thin films. PMID- 9978029 TI - Asymptotic critical behavior of Ni. PMID- 9978028 TI - Thermodynamics of the exactly solvable two-chain and multichain quantum spin models. PMID- 9978030 TI - Experimental and theoretical study of extremely dilute Sc and Fe impurities in Gd and Tb. PMID- 9978031 TI - Magnetic phases of the two-dimensional Hubbard model at low doping. PMID- 9978032 TI - Magnetic properties of the dipolar Heisenberg antiferromagnet Gd in GdBa2Cu3O6+x. PMID- 9978033 TI - Spin-resolved substrate band mapping in Fe/Cu(100): Application of the spin filter effect. PMID- 9978034 TI - Band-theoretical investigation of the magneto-optical Kerr effect in Fe and Co multilayers. PMID- 9978035 TI - Pressure effects and specific heat in superconducting HoNi2B2C. PMID- 9978036 TI - Temperature dependence of even-odd electron-number effects in the single-electron transistor with a superconducting island. PMID- 9978037 TI - Phase transition in the lattice Coulomb gas. PMID- 9978038 TI - Effect of an interband interaction on narrow-band superconductivity. PMID- 9978039 TI - Thermal expansion and magnetostriction of superconducting URu2Si2. PMID- 9978040 TI - Superconductivity in spinel-type compounds CuRh2S4 and CuRh2Se4. PMID- 9978041 TI - Soliton localization in disordered one-dimensional Josephson transmission lines. PMID- 9978043 TI - Density-density response of dilute 3He-4He mixtures at low temperatures. PMID- 9978042 TI - Inductance effects and dimensionality crossover in hybrid superconducting arrays. PMID- 9978044 TI - Influence of oxygen stoichiometry on the irreversible magnetization and flux creep in RBa2Cu3O7- delta (R=Y,Tm) single crystals. PMID- 9978045 TI - Semiempirical estimation of the intermolecular electron-phonon coupling in K3C60 and Rb3C60. PMID- 9978046 TI - Critical behavior of superfluid 4He films adsorbed in aerogel glass. PMID- 9978047 TI - Effect of memory and dynamical chaos in long Josephson junctions. PMID- 9978048 TI - Charge and spin ordering in La2-xSrxNiO4.00 with x=0.135 and 0.20. PMID- 9978049 TI - Cation distributions and possible phase separation in Tl2Ba2CuO6+ delta from synchrotron powder x-ray diffraction. PMID- 9978050 TI - Field-induced granularity in a well-textured (Bi,Pb)2Sr2Ca2Cu3Oy tape. PMID- 9978051 TI - Determination of oxygen content and cation valences in superconducting Tl-based cuprates by a wet chemical method. PMID- 9978052 TI - Effect of columnar defects on the elastic behavior of vortices in YBa2Cu3O7- delta thin films. PMID- 9978053 TI - Relation of local Cu2+ spins, crystal microstructure, and charge transport in the CuO2 plane in Bi2Sr2CuOy. PMID- 9978055 TI - Influence of a surface-depressed order parameter on the Josephson critical current in Bi2Sr2CaCu2O8+x nonhysteretic break junctions. PMID- 9978054 TI - Time dependence of the paramagnetic Meissner effect: Comparison between model calculations and experiments. PMID- 9978057 TI - Effective Coulomb interactions between doped carriers in the high-Tc cuprates. PMID- 9978056 TI - Unpaired vortices and layer decoupling in quasi-two-dimensional superconductors: A model calculation. PMID- 9978058 TI - Frenkel excitons in random systems with correlated Gaussian disorder. PMID- 9978060 TI - Strong evidence of an isotope effect in the diffusion of a NaCl and CsCl solution. PMID- 9978059 TI - Scattering times and mean free path in AlCuFe quasicrystalline thin films. PMID- 9978062 TI - Phase locking in a thermostat: Fermi resonance in metals. PMID- 9978061 TI - Energy spectra and level statistics of Fibonacci and Thue-Morse chains. PMID- 9978063 TI - Inverse magnetoresistance in the simple spin-valve system Fe1-xVx/Au/Co. PMID- 9978064 TI - Phonon anomalies at the magnetic phase transition in SrRuO3. PMID- 9978065 TI - Magnetic and nonmagnetic Ce in the borocarbides. PMID- 9978066 TI - Simple theory of giant magnetoresistance in a magnetic trilayer. PMID- 9978067 TI - Magnetism of 4d and 5d adlayers on Ag(001) and Au(001): Comparison between a nonrelativistic and a fully relativistic approach. PMID- 9978068 TI - Quantum effects on the Berezinskii-Kosterlitz-Thouless transition in the ferromagnetic two-dimensional XXZ model. PMID- 9978069 TI - Positive field-cooled dc susceptibility in granular superconductors interpreted through numerical simulations on a simple Josephson-junction-array model. PMID- 9978070 TI - Composition dependence of the oxygen isotope effect in Ba1-xKxBiO3: Evidence for oxygen-mass dependence of the coupling constant. PMID- 9978072 TI - Role of orthorhombic distortion, second-nearest-neighbor hopping, and Coulomb repulsion on the superconducting transition temperature and isotope-shift exponent. PMID- 9978071 TI - Superconducting anisotropy of YNi2B2C. PMID- 9978073 TI - Roton-pair creation by electron bubbles in helium. PMID- 9978075 TI - Dynamics of supercooled water: Mode-coupling theory approach. PMID- 9978074 TI - Dissipation in high-temperature superconductors: From short- to long-range percolative order. PMID- 9978076 TI - Supercooled liquid dynamics for the charged hard-sphere model. PMID- 9978077 TI - Calculation of the strain-induced shifts in the infrared-absorption peaks of cubic boron nitride. PMID- 9978078 TI - Selection rules for oscillations of the interlayer exchange coupling as a function of ferromagnet thickness. PMID- 9978079 TI - Unrestricted Hartree-Fock study of transition-metal oxides: Spin and orbital ordering in perovskite-type lattice. PMID- 9978080 TI - Giant anomalies of the thermal expansion at the spin-Peierls transition in CuGeO3. PMID- 9978081 TI - Evidence of dilution-induced Griffiths instabilities in K2Cu1-xZnxF4 and Fe1 xZnxF2. PMID- 9978082 TI - More evidence for magnetic ordering in CeCu6 at mK temperatures. PMID- 9978083 TI - Exactly solvable nonequilibrium Kondo problem. PMID- 9978085 TI - Tunnel junctions of unconventional superconductors. PMID- 9978084 TI - Origin of the R-ion effect on Tc in RBa2Cu3O7. PMID- 9978086 TI - Flux-line crossing in the vortex-liquid phase of YBa2Cu3O7- delta. PMID- 9978087 TI - Generic superconducting phase behavior in high-Tc cuprates: Tc variation with hole concentration in YBa2Cu3O7- delta. PMID- 9978088 TI - Interplay between electron-electron interactions and impurities in one dimensional rings. PMID- 9978089 TI - Construction of tight-binding-like potentials on the basis of density-functional theory: Application to carbon. PMID- 9978090 TI - Ground-state properties of ordered, partially ordered, and random Cu-Au and Ni-Pt alloys. PMID- 9978091 TI - Organization of infrared effects in the resonating-valence-bond gauge theory. PMID- 9978092 TI - Impurity-induced modulations in NbSe3 detected by atomic-force microscopy. PMID- 9978093 TI - Mean-field energies of spin-flux phases. PMID- 9978094 TI - Electronic structure of organic superconductors kappa -(ET)2Cu PMID- 9978096 TI - Ensuring the constancy of the chemical potential within the local-density approximation for exchange and correlation: Implications for near-edge x-ray absorption fine structure. PMID- 9978095 TI - Detailed microscopic calculation of phonon-mediated electron-electron scattering in aluminum. PMID- 9978097 TI - Electronic and optical properties of three phases of titanium dioxide: Rutile, anatase, and brookite. PMID- 9978098 TI - Lanczos-type algorithm for excited states of very-large-scale quantum systems. PMID- 9978099 TI - Proof for an upper bound in fixed-node Monte Carlo for lattice fermions. PMID- 9978100 TI - Consistent bosonization treatment of interacting fermion systems in dimensions higher than one: Requirement for a Luttinger-liquid state. PMID- 9978101 TI - Integral thermodynamic properties of Mo and W in the nonempirical effective potential approach. PMID- 9978102 TI - Correlation effect on magnetoconductance in the strongly localized regime with spin-orbit interaction. PMID- 9978103 TI - Electronic correlations in the excited states of the Hubbard model on a tetrahedron. PMID- 9978104 TI - Perturbation approach to the reflection and transmission of light. PMID- 9978106 TI - Conformational influence on the hopping conductivity in pig insulin. PMID- 9978105 TI - Observation of high-temperature spin-freezing behavior in Cd1-x-yMnxFeyTe. PMID- 9978107 TI - E1, E2, and E0' transitions and pressure dependence in ordered Ga0.5In0.5P. PMID- 9978109 TI - Tight-binding study of the {113} planar interstitial defects in Si. PMID- 9978108 TI - Visible photoluminescence from silicon-backbone polymers. PMID- 9978110 TI - Muon-spin-resonance study of muonium dynamics in Si and its relevance to hydrogen. PMID- 9978112 TI - Dynamic bond-strength variation for hydrogen-donor pairs in semiconductors. PMID- 9978111 TI - First-principles calculations of the energy barrier to dislocation motion in Si and GaAs. PMID- 9978113 TI - Relativistic electronic structure, effective masses, and inversion-asymmetry effects of cubic silicon carbide (3C-SiC). PMID- 9978114 TI - Conduction- and valence-band effective masses in spontaneously ordered GaInP2. PMID- 9978115 TI - Grating-induced cyclotron-resonance anomaly in GaAs/AlxGa1-xAs heterostructures. PMID- 9978117 TI - Internal photoemission spectroscopy for a PtSi/p-type Si Schottky-barrier diode. PMID- 9978116 TI - Optical linewidth and field fluctuations in piezoelectric quantum wells. PMID- 9978118 TI - Second-order optical susceptibility of biased quantum wells in the interband regime. PMID- 9978119 TI - Influence of electrode Fermi energy on interband tunneling. PMID- 9978120 TI - Calculation and photoresponse measurement of the bound-to-continuum infrared absorption in p-type GaAs/AlxGa1-xAs quantum wells. PMID- 9978121 TI - Influence of interface localization on the binding energy of acceptor bound excitons in narrow GaAs/AlxGa1-xAs quantum wells. PMID- 9978122 TI - Mesoscopic mechanisms of the photovoltaic effect and microwave absorption in granular metals. PMID- 9978124 TI - Domain-boundary-induced metastable reconstructions during epitaxial growth of Si/Si(111). PMID- 9978123 TI - Raman spectra of GaAs with ultrathin InAs layers inserted. PMID- 9978126 TI - Defects generated by misfit strain in SiGe/Si(001). PMID- 9978125 TI - Thermoelectric figure of merit of composite superlattice systems. PMID- 9978127 TI - High-pressure study of the deformation potentials of Cd1-xZnxTe/ZnTe quantum wells via photoluminescence. PMID- 9978128 TI - Temperature dependence of photoconductivity and noise in CdS-based devices. PMID- 9978129 TI - Magnetotransport of a two-dimensional electron gas in a spatially random magnetic field. PMID- 9978130 TI - Optical investigations in (In,Ga)As/GaAs quantum wells grown by metalorganic molecular-beam epitaxy. PMID- 9978132 TI - LO-phonon emission in an AlxGa1-xAs-GaAs-AlyGa1-yAs single quantum well with two occupied electronic subbands. PMID- 9978131 TI - Reduced electron-phonon relaxation rates in quantum-box systems: Theoretical analysis. PMID- 9978133 TI - Temperature dependence of luminescence efficiency, exciton transfer, and exciton localization in GaAs/AlxGa1-xAs quantum wires and quantum dots. PMID- 9978135 TI - Rocking-curve analysis of reflection high-energy electron diffraction from the Si(111)-( sqrt 3 x sqrt 3 )R30 degrees-Al, -Ga, and -In surfaces. PMID- 9978134 TI - Theoretical investigation of the effect of a magnetic field on the Landau-level structure of a modulation-doped single heterojunction having two occupied subbands. PMID- 9978136 TI - Optically detected magnetic resonance of GaN films grown by organometallic chemical-vapor deposition. PMID- 9978138 TI - 1s-2p+/- infrared-absorption spectra of donor-doped quantum wells under electric and magnetic fields. PMID- 9978137 TI - Avalanche amplification of multiple resonant tunneling through parallel silicon microcrystallites. PMID- 9978139 TI - Intersubband optical response of semiconductor quantum wells dressed by strong infrared fields. PMID- 9978140 TI - Dressed S matrices in models with long-range interactions. PMID- 9978141 TI - Ab initio calculations of SiC(110) and GaAs(110) surfaces: A comparative study and the role of ionicity. PMID- 9978142 TI - Intervalley scattering in GaAs/AlAs resonant-tunneling diodes. PMID- 9978143 TI - Hydrodynamic electron flow in high-mobility wires. PMID- 9978144 TI - Mesoscopic fluctuations of eigenfunctions and level-velocity distribution in disordered metals. PMID- 9978145 TI - Fano resonances in the magnetoresistance of a quantum wire doped with magnetic impurities. PMID- 9978146 TI - Single-particle states on a sphere with a magnetic field and disorder. PMID- 9978147 TI - Direct pathway for sticking/desorption of H2 on Si(100). PMID- 9978148 TI - Persistent spin currents induced by the Aharonov-Casher effect in mesoscopic rings. PMID- 9978149 TI - Impurity scattering and transport of fractional quantum Hall edge states. PMID- 9978150 TI - Acoustic excitations of a confined two-dimensional electron liquid in a magnetic field. PMID- 9978151 TI - Collective modes of soliton-lattice states in double-quantum-well systems. PMID- 9978152 TI - Bipolar charge redistribution in resonant-tunneling light-emitting diodes. PMID- 9978153 TI - Cyclotron-resonance measurements on p-type strained-layer Si1-xGex/Si heterostructures. PMID- 9978154 TI - Structural study of the close-packed two-dimensional phases of Pb on Ge(111) and Si(111). PMID- 9978155 TI - UV reflectivity of GaN: Theory and experiment. PMID- 9978157 TI - Quasiparticle bands in a two-dimensional crystal found by GW and quantum Monte Carlo calculations. PMID- 9978156 TI - Transverse diffusion of minority carriers confined near the GaAs surface plane. PMID- 9978158 TI - Green's-function calculations of valence photoemission spectra of Pd2CO and Pt2CO. PMID- 9978159 TI - Multifractal behavior of the distribution of secondary-electron-emission sites on solid surfaces. PMID- 9978160 TI - Theory of ultrashort nonlinear multiphoton photoelectric emission from metals. PMID- 9978161 TI - Theory of friction: Stress domains, relaxation, and creep. PMID- 9978162 TI - Electronic structure of La-intercalated graphite. PMID- 9978163 TI - Reconstructive adsorption of Na on Al(111) studied by scanning tunneling microscopy. PMID- 9978165 TI - Structural rearrangements in the C/W(001) surface system. PMID- 9978164 TI - Brillouin-zone-selection effects in graphite photoelectron angular distributions. PMID- 9978166 TI - Properties of small clusters at ionic surfaces: (NaCl)n clusters (n=1-48) at the (100) MgO surface. PMID- 9978167 TI - Direct atomic imaging of Ag(100) and Ag(111) by inverting quasielastically scattered electron-diffraction patterns. PMID- 9978168 TI - Density-functional calculation of the bulk and surface geometry of beryllium. PMID- 9978169 TI - Uncertainty, topography, and work function. PMID- 9978170 TI - Experimental interatomic Auger rates in sodium halides. PMID- 9978172 TI - Near-field scattering from subwavelength metallic protuberances on conducting flat substrates. PMID- 9978171 TI - Valence-band structure of alkali halides determined from photoemission data. PMID- 9978173 TI - Structure, melting, and order tendencies of A13B13 Lennard-Jones heteroclusters with additive and nonadditive collision diameters. PMID- 9978174 TI - Simulation of the melting behavior of small silicon clusters. PMID- 9978175 TI - Atomic clusters: Building blocks for a class of solids. PMID- 9978176 TI - Casimir forces between spherical particles in a critical fluid and conformal invariance. PMID- 9978177 TI - Theory of the multiphoton photoelectric effect: A stepwise excitation process. PMID- 9978178 TI - Anharmonic localized surface vibrations in a scalar model. PMID- 9978180 TI - Contributions of higher angular momentum states to lateral resolution in scanning tunneling microscopy. PMID- 9978179 TI - Interaction of hydrogen with the Be(0001) surface. PMID- 9978181 TI - Temperature dependence of the rate of defect tunneling in metals. PMID- 9978182 TI - Femtosecond spectral relaxation of alpha -conjugated hexamethylsexithiophene in solution. PMID- 9978183 TI - Phase diagram of an extended Hubbard model with correlated hopping at half filling. PMID- 9978185 TI - Orthogonality catastrophe and non-Fermi liquids. PMID- 9978184 TI - Polymorphism of carbon forms: Polyhedral morphology and electronic structures. PMID- 9978186 TI - Magnetic perturbations of excitons bound to an isoelectronic hydrogen-related defect in silicon. PMID- 9978188 TI - Interpretation of near-band-edge photoreflectance spectra from CdTe. PMID- 9978187 TI - Stress effects on HgI2 optical properties. PMID- 9978189 TI - Observation of the effect of electron-electron scattering on the impurity-limited resistivity of a two-dimensional electron gas. PMID- 9978190 TI - Effect of superlattice structure on the thermoelectric figure of merit. PMID- 9978191 TI - Surface elastic waves in superlattices: Sagittal localized and resonant modes. PMID- 9978192 TI - Observation of lateral electrostatic quantum-interference effects in a AlxGa1 xAs/GaAs heterostructure. PMID- 9978194 TI - Self-sustained Aharonov-Bohm flux in mesoscopic rings: Continuum hard-core boson model. PMID- 9978193 TI - Carrier lifetime in deep-etched InxGa1-xAs/InP quantum wires. PMID- 9978196 TI - Localization in semiconductor quantum-wire nanostructures. PMID- 9978195 TI - Quadrupole excitations of quantum dots. PMID- 9978197 TI - Forward-electron-scattering study of the surface structure and phase transition on W(001). PMID- 9978198 TI - One-electron contributions to the surface core-level shifts in transition metals. PMID- 9978199 TI - Electronic structures of giant fullerenes with Ih symmetry. PMID- 9978200 TI - Electronic structure and transport properties of fullerene nanotubules. PMID- 9978201 TI - Correction of experimental low-energy electron-diffraction intensities. PMID- 9978202 TI - He adsorption and intercalation in C60 fullerite crystals. PMID- 9978204 TI - Structure of the Si12 cluster. PMID- 9978203 TI - Strong-field magnetoresistance anisotropy in thin composite films with a periodic microstructure. PMID- 9978205 TI - Ferromagnetism of 4d and 5d transition-metal monolayers on Ag(111). PMID- 9978206 TI - Localized Ba 4d and 5p excitations above the ionization limit observed in BaF2. PMID- 9978207 TI - Transport properties of coupled one-dimensional interacting electron systems with impurities. PMID- 9978209 TI - Luminescence from excited states in strain-induced InxGa1-xAs quantum dots. PMID- 9978208 TI - Light-induced relaxing dipoles in n-type AlxGa1-xAs. PMID- 9978210 TI - Single electron switching in a parallel quantum dot. PMID- 9978211 TI - Time-resolved photoluminescence of a two-dimensional hole system in the extreme quantum limit. PMID- 9978213 TI - Giant backscattering peak in angle-resolved Andreev reflection. PMID- 9978212 TI - Microscopic structure of the GaAs(001)-(6 x 6) surface derived from scanning tunneling microscopy. PMID- 9978214 TI - Enhanced energy and phase relaxation of excitons in the presence of bare electrons. PMID- 9978216 TI - Spin-polarized photoemission studies of the exchange splitting of the Gd 5d electrons near the Curie temperature. PMID- 9978215 TI - Phonon contribution to quasiparticle lifetimes in Cu measured by angle-resolved photoemission. PMID- 9978217 TI - Fermi-liquid versus Luttinger-liquid behavior and metal-insulator transition in N,N'-dicyanoquinonediimine-Cu salt studied by photoemission. PMID- 9978218 TI - Erratum: Adsorbate symmetry and Fermi resonances of methoxide adsorbed on Mo(110) as studied by surface infrared spectroscopy PMID- 9978219 TI - Ionization energy for charged particles in Ge. PMID- 9978220 TI - Equilibrium-density equation for classical interacting particles. PMID- 9978222 TI - X-ray-absorption spectroscopic studies of sodium polyphosphate glasses. PMID- 9978221 TI - Effect of turbostratic disorder in graphitic carbon hosts on the intercalation of lithium. PMID- 9978223 TI - Short-range atomic structure of 1 wt. % Ga delta -stabilized plutonium by x-ray absorption fine-structure spectroscopy. PMID- 9978224 TI - Crystallization mechanism of dehydrated amorphous LiBO2. PMID- 9978225 TI - Optical study on the phase transition of lead lanthanum zirconate titanate Pb0.92La0.08(Zr0.70Ti0.30)0.98O3 ceramics. PMID- 9978226 TI - Low-temperature phase transformation in Li-10 at. % Mg. PMID- 9978227 TI - Excited-state-absorption and upconversion studies of Nd3+-doped single crystals Y3Al5O12, YLiF4, and LaMgAl11O19. PMID- 9978229 TI - XAFS near-edge structure of As2S3: A comparison of experiment and theory. PMID- 9978228 TI - Anisotropic covalent bonding and photopolymerization of C70. PMID- 9978231 TI - Correlated static atomic displacements and transmission-electron-microscopy contrast in compositionally homogeneous disordered alloys. PMID- 9978230 TI - Dielectric echo experiments on (KBr)1-x(KCN)x. PMID- 9978232 TI - Evolution of phases and microstructure in Fe81B13.5Si3.5C2 metallic glass during electron-beam and pulsed-laser irradiation. PMID- 9978233 TI - Structure and properties of nonconventional glasses in the binary bismuth cuprate system. PMID- 9978234 TI - Prediction of the external shape of ideal icosahedral quasicrystals. PMID- 9978235 TI - Propagation of carriers in a one-dimensional quasicrystal. PMID- 9978236 TI - First-principles molecular dynamics of liquid cesium and rubidium. PMID- 9978237 TI - Incoherent exciton trapping in self-similar aperiodic lattices. PMID- 9978239 TI - Spin-lattice relaxation of F centers in mixed alkali halides: KBrxCl1-x. PMID- 9978238 TI - Electrical resistivity of a fractal network: The scattering of extended electronic states by both fractons and phonons. PMID- 9978240 TI - Quantum electron dynamics in periodic and aperiodic sequences. PMID- 9978242 TI - Explanation of anomalous polariton dynamics in LiTaO3. PMID- 9978241 TI - Squeezed excited states in exciton-phonon systems. PMID- 9978243 TI - Nuclear quadrupole spin-lattice relaxation in anharmonic molecular crystals. PMID- 9978244 TI - Use of finite size and applied magnetic field to characterize the interimpurity interaction in a spin glass. PMID- 9978245 TI - Influence of temperature and magnetic field on ferrimagnetic CePtGe2. PMID- 9978247 TI - Static thermodynamic quantities of quantum Heisenberg spin glasses with anisotropic interaction in applied magnetic fields. PMID- 9978246 TI - Ordered phase for the infinite-range Potts-glass model. PMID- 9978248 TI - Magnetic susceptibility of a real ferromagnet near the coexistence condition. PMID- 9978250 TI - Dynamics of vortices in a two-dimensional easy-plane antiferromagnet. PMID- 9978249 TI - Weak suppression of ferromagnetism in tetrakis(dimethylamino)ethylene-(C60)1 x(C70)x. PMID- 9978251 TI - Spin-wave theory of impurity states near the interface between two ferromagnets. PMID- 9978252 TI - Two-magnon absorption of electromagnetic waves in the exchange noncollinear antiferromagnet Nd2CuO4. PMID- 9978253 TI - Phase diagram of ultrathin ferromagnetic films with perpendicular anisotropy. PMID- 9978254 TI - Enhanced Fe 3d spectral weight near the Fermi level in Fe overlayers on Cr. PMID- 9978255 TI - Local-spin-selective x-ray absorption and x-ray magnetic circular dichroism of MnP. PMID- 9978256 TI - Raman study of Kramers doublets in Nd2CuO4. PMID- 9978257 TI - Theoretical aspects of the FecNi1-c Invar alloy. PMID- 9978258 TI - Electronic structures and Curie temperatures of iron-based rare-earth permanent magnet compounds. PMID- 9978260 TI - Theory of finite-size effects and vortex penetration in small Josephson junctions. PMID- 9978259 TI - Proximity effect in superconductor-insulator-superconductor Josephson tunnel junctions: Theory and experiment. PMID- 9978261 TI - LUMO band of K-doped C60 single phases: A photoemission and yield-spectroscopy study. PMID- 9978262 TI - Electronic structure of a vortex line in a type-II superconductor: Effect of atomic crystal fields. PMID- 9978263 TI - Enhancement of electron-phonon interactions in the nonequilibrium solid solutions Al1-xSix. PMID- 9978264 TI - Renormalized theory of repulsive bosons in two dimensions. PMID- 9978265 TI - Weak-link magnetically modulated resistance response in granular superconducting systems. PMID- 9978266 TI - Incompressible quantum Hall states in Josephson-junction arrays. PMID- 9978267 TI - Thermoelectric flux in superconducting hollow cylinders. PMID- 9978268 TI - Cavitation in 3He-4He liquid mixtures at low temperatures. PMID- 9978270 TI - Density of states of a layered S/N d-wave superconductor. PMID- 9978269 TI - Collective modes of spin, density, phase, and amplitude in exotic superconductors. PMID- 9978271 TI - Phase diagrams of the electronic state of the one-dimensional d-p model. PMID- 9978273 TI - Different Pr3+ environments in Pr1.85Ce0.15CuO4: A Raman crystal-field excitation study. PMID- 9978272 TI - Quantum depinning of flux lines from columnar defects. PMID- 9978274 TI - Condensate pair fluctuations in a two-dimensional d-wave superconductor and Raman scattering. PMID- 9978275 TI - Evidence for a vortex-liquid-vortex-glass transition in epitaxial Bi2Sr2Ca2Cu3O10+ delta thin films. PMID- 9978277 TI - Ergodic versus nonergodic behavior in oxygen-deficient high-Tc superconductors. PMID- 9978276 TI - Cluster-configuration-interaction analysis of Cu 2p and valence-band photoemission measurements on Bi2Sr2CaCu2O8 and Bi2Sr2CuO6 superconductors. PMID- 9978278 TI - Gaplessness and properties of layered superconductors: Application to high-Tc cuprates. PMID- 9978279 TI - Low-frequency suppression of random-telegraph-noise spectra in high-temperature superconductors. PMID- 9978280 TI - Thermal fluctuations and critical current in twinned single crystals. PMID- 9978281 TI - Isothermal phase transition and elastic energy dissipation in YBa2Cu3O6+x. PMID- 9978282 TI - X-ray-absorption studies of electron doping and band shifts in R2-xCexCuO4- delta (R=Pr, Nd, Sm, Eu, and Gd). PMID- 9978283 TI - Flux pinning and critical current in layered type-II superconductors in parallel magnetic fields. PMID- 9978284 TI - Zn, Ce, Pr, and Th doping in YBa2Cu4O8. PMID- 9978285 TI - Sum rules for polarization-dependent x-ray absorption. PMID- 9978287 TI - Ground state and vibrations of dipoles on a honeycomb lattice. PMID- 9978286 TI - Pressure dependence of phase-transition temperatures in oxygenated single crystalline La2CuO4.035. PMID- 9978288 TI - 19F ligand hyperfine structure in the room-temperature electron-paramagnetic resonance spectra of Mn2+ substituting for Zr4+ sites in Cd2ZrF8 PMID- 9978289 TI - Magnetic phases in UCu2Ge2. PMID- 9978290 TI - Nuclear Schottky effect in thulium. PMID- 9978291 TI - Spin configurations of pi electrons in quasi-one-dimensional organic ferromagnets. PMID- 9978292 TI - Magnetoresistance behavior of ternary Ce alloys. PMID- 9978293 TI - Influence of thermal fluctuations on single-vortex pinning in Rb3C60 fullerene superconductors. PMID- 9978295 TI - Collective pinning of vortices in very thin amorphous Mo79Ge21 films. PMID- 9978294 TI - Hubbard model and fullerenes: Stability of the Nagaoka state. PMID- 9978296 TI - Confined and extended optical phonons in an ultrathin-layer YBa2Cu3O7/PrBa2Cu3O7 superlattice. PMID- 9978297 TI - Landau damping in high-temperature superconductors. PMID- 9978298 TI - Thermoelectric power and resistivity measurements on oxygen-annealed HgBa2Ca2Cu3O8+ delta superconductors. PMID- 9978300 TI - Symmetries of the superconducting order parameter arising from an interlayer tunneling mechanism. PMID- 9978299 TI - Thermally activated behavior of 1/f noise in YBa2Cu3O7- delta. PMID- 9978301 TI - Enhancement of persistent photoconductivity in insulating high-Tc thin films. PMID- 9978302 TI - Raman study of YBa2Cu3O7-x single crystals grown by a pulling technique: Overdoped, underdoped, and nonsuperconducting state. PMID- 9978303 TI - Origin of zero-bias conductance peaks in high-Tc superconductors. PMID- 9978304 TI - 35Cl spin-lattice relaxation in incommensurate bis(4-chlorophenyl)sulfone. PMID- 9978305 TI - Orientationally ordered states in solid C60. PMID- 9978306 TI - Fast oscillations in the surface impedance of (TMTSF)2ClO4 in a magnetic field. PMID- 9978307 TI - Complete optical response of the magnetic fullerene derivative tetrakis(dimethylamino)ethylene-C60. PMID- 9978308 TI - Coster-Kronig contributions to magnetic circular dichroism in the L2,3 x-ray fluorescence of iron. PMID- 9978309 TI - Interference effects on the critical current in a clean-limit superconductor normal-metal-superconductor junction. PMID- 9978310 TI - Spin-paramagnetic transition of ultrathin granular Al films in a tilted magnetic field. PMID- 9978311 TI - Quasiparticle spectrum in the high-Tc superconducting state. PMID- 9978312 TI - Electronic band structure of the superconductor Sr2RuO4. PMID- 9978313 TI - Vortex channeling along twin planes in YBa2Cu3O7-x. PMID- 9978314 TI - Transport studies of bulk Pb0.2Hg0.8Ba2Ca1.75Cu3Ox. PMID- 9978315 TI - Superconducting energy gap in Bi1.8Pb0.4Sr2Ca2Cu3O10+ delta studied by photoemission spectroscopy. PMID- 9978316 TI - c-axis microwave conductivity of YBa2Cu3O7- delta in the superconducting state. PMID- 9978317 TI - Order-N density-matrix electronic-structure method for general potentials. PMID- 9978318 TI - Electronic structure of La1-xSrxMnO3 studied by photoemission and x-ray absorption spectroscopy. PMID- 9978319 TI - Soft-x-ray linear-dichroism and magnetic-circular-dichroism studies of CeRh3B2: Large crystal-field splitting and anomalous ferromagnetism. PMID- 9978320 TI - Defect structures in a layer-by-layer photonic band-gap crystal. PMID- 9978321 TI - Influence of superexchange on Ni 2p x-ray-absorption spectroscopy in NiO. PMID- 9978322 TI - Electronic structure of antimony-doped tin oxide. PMID- 9978324 TI - Orbital polarization in metallic f-electron systems. PMID- 9978323 TI - Signatures of Fano resonances in four-wave-mixing experiments. PMID- 9978325 TI - Dominant density parameters and local pseudopotentials for simple metals. PMID- 9978326 TI - Single-particle spectral function of a generalized Hubbard model: Metal-insulator transition. PMID- 9978327 TI - Hopping transport in a magnetic field: Kadanoff-Baym-Keldysh approach and magnetoconductivity. PMID- 9978328 TI - Experimental and theoretical electronic distributions in Al-Cu-based alloys. PMID- 9978330 TI - Real-space electronic-structure calculations: Combination of the finite difference and conjugate-gradient methods. PMID- 9978329 TI - Electronic structure and total-energy calculations by a semi-self-consistent augmented-plane-wave method. PMID- 9978331 TI - Charge-transfer multiplet analysis of the resonant 2p3p3p Auger spectra of CaF2. PMID- 9978332 TI - Quasiparticle spectra and the calculation of thermodynamics for a two-dimensional Fermi liquid. PMID- 9978333 TI - High-temperature series expansion for the extended Hubbard model. PMID- 9978334 TI - Electronic transport through a planar defect in the bulk. PMID- 9978335 TI - Photoelectron spectroscopy of strongly correlated systems: Effects of nonlocal interactions. PMID- 9978336 TI - Insulator-metal transition and giant magnetoresistance in La1-xSrxMnO3. PMID- 9978338 TI - Photothermal reflection versus temperature: Quantitative analysis. PMID- 9978337 TI - Theory of reflectance-difference spectroscopy in ordered III-V semiconductor alloys. PMID- 9978340 TI - Intervalley electron scattering in the presence of a planar interface. PMID- 9978339 TI - Free magnetic polaron: A nonlinear Hamiltonian approach. PMID- 9978341 TI - Deep levels in hafnium- and zirconium-doped indium phosphide. PMID- 9978342 TI - Monte Carlo study of the statistics of electron capture by shallow donors in silicon at low temperatures. PMID- 9978343 TI - Introduction of metastable vacancy defects in electron-irradiated semi-insulating GaAs. PMID- 9978344 TI - Hierarchy of density matrices in coherent semiconductor optics. PMID- 9978346 TI - Ultrafast laser-induced order-disorder transitions in semiconductors. PMID- 9978345 TI - Zero-field-splitting parameters of Cr2+ ion in GaAs. PMID- 9978347 TI - Polarized electroabsorption spectroscopy of highly ordered poly(2-methoxy,5-(2' ethyl-hexoxy)-p-phenylene vinylene). PMID- 9978348 TI - Transient nonlinear electrical transport of hot electrons in nonpolar semiconductors. PMID- 9978349 TI - Damped Ruderman-Kittel-Kasuya-Yosida interaction among local magnetic moments in the impurity-band regime of doped semiconductors. PMID- 9978350 TI - Photoacoustic investigation of transport in semiconductors: Theoretical and experimental study of a Ge single crystal. PMID- 9978352 TI - Nonequilibrium total-dielectric-function approach to the electron Boltzmann equation for inelastic scattering in doped polar semiconductors. PMID- 9978351 TI - Nonequilibrium dynamics of hot carriers and hot phonons in CdSe and GaAs. PMID- 9978353 TI - Electron-electron interactions, coupled plasmon-phonon modes, and mobility in n type GaAs. PMID- 9978354 TI - Chemistry at the Al- and Au-ZnSe(100) interfaces. PMID- 9978355 TI - InAs(110)-p(1 x 1)-Sb(1 ML): Electronic structure and surface bonding. PMID- 9978356 TI - Precise nonequilibrium distribution function for a one-dimensional electron gas. PMID- 9978357 TI - Interaction of oxygen with a Rb-covered InSb(111) surface. PMID- 9978358 TI - Formation of facets and pyramidlike structures in molecular-beam-epitaxy growth of Si on a singular Si(111) surface. PMID- 9978359 TI - Direct and Rb-promoted SiOx/ beta -SiC(100) interface formation. PMID- 9978360 TI - Free-carrier and intersubband infrared absorption in p-type Si1-xGex/Si multiple quantum wells. PMID- 9978361 TI - Ellipsometric and thermoreflectance spectra of epitaxial InSb films. PMID- 9978362 TI - Enhancement of nonradiative recombination due to resonant electron capture in AlxGa1-xAs/GaAs quantum-well structures. PMID- 9978364 TI - Theory of the interface exciton in a strong magnetic field. PMID- 9978363 TI - Shape transition in the epitaxial growth of gold silicide in Au thin films on Si(111). PMID- 9978365 TI - Choking of electron flow: A mechanism of current saturation in field-effect transistors. PMID- 9978367 TI - Theoretical study of strained thin quantum wells grown on vicinal surfaces. PMID- 9978366 TI - Energy levels and exciton oscillator strength in submonolayer InAs-GaAs heterostructures. PMID- 9978368 TI - Coherent vertical transport of excitons in multiple quantum wells. PMID- 9978369 TI - Excitons in self-organized semiconductor/insulator superlattices: PbI-based perovskite compounds. PMID- 9978370 TI - Nonlocal optical response of assemblies of semiconductor spheres. PMID- 9978371 TI - Excitons and fundamental absorption in quantum wells. PMID- 9978372 TI - High-frequency damping of plasmons in quasi-one-dimensional electron systems. PMID- 9978373 TI - Exciton Stark and Landau ladders in a GaAs/AlxGa1-xAs superlattice. PMID- 9978374 TI - Nonlinear steady-state mesoscopic transport: Formalism. PMID- 9978375 TI - Microcavity exciton-polariton splitting in the linear regime. PMID- 9978377 TI - Comparison of the (2 x 2) reconstructions of GaAs{111} surfaces. PMID- 9978376 TI - Selection rules and dispersion of GaAs/AlAs multiple-quantum-well optical phonons studied by Raman scattering in right-angle, forward, and backscattering in-plane geometries. PMID- 9978378 TI - Structural and electronic properties during the initial stages of Ge-GaAs(110) interface formation. PMID- 9978380 TI - Conductance fluctuations in a disordered double-barrier junction. PMID- 9978379 TI - Fractional exclusion statistics and anyons. PMID- 9978382 TI - Capacitance of electron wires in a high magnetic field. PMID- 9978381 TI - Coherent effects induced by static and time-dependent electric fields in semiconductors. PMID- 9978383 TI - Theoretical study of the Si(100) surface reconstruction. PMID- 9978385 TI - Multiphonon-assisted tunneling through deep levels: A rapid energy-relaxation mechanism in nonideal quantum-dot heterostructures. PMID- 9978384 TI - Low-temperature transport of excitons in type-II GaAs/AlAs quantum wells. PMID- 9978386 TI - Magneto-optical study of quantum-well electronic structure using disorder-induced resonant acoustic-phonon Raman scattering. PMID- 9978387 TI - Small-cone method of directly forming atomic images from energy-dependent photoelectron-diffraction data. PMID- 9978388 TI - Growth mechanisms and defects in boronated CVD diamond as identified by scanning tunneling microscopy. PMID- 9978390 TI - Spin-flip scattering for the electrical property of metallic-nanoparticle thin films. PMID- 9978389 TI - Model study of keV-ion mixing of metallic interfaces: Influence of materials properties and deposited energy. PMID- 9978391 TI - Calculated properties of a prototypical ionic monolayer. PMID- 9978392 TI - Hidden structure of the low-energy spectrum of a one-dimensional localized Frenkel exciton. PMID- 9978393 TI - Evidence for the leading role of the stacking-fault triangle in the Si(111) 1 x 1 ->7 x 7 phase transition. PMID- 9978394 TI - Interpretation of the control of the photon emission stimulated by STM. PMID- 9978396 TI - Wetting on rough self-affine surfaces. PMID- 9978395 TI - Theory of ion-stimulated electron emission from simple metals: Explicit calculations. PMID- 9978398 TI - Finite-conical-well model for vertically adsorbed diatomic molecules. PMID- 9978397 TI - First-principles studies of NO chemisorption on rhodium, palladium, and platinum surfaces. PMID- 9978399 TI - Melting transition in two dimensions: A finite-size scaling analysis of bond orientational order in hard disks. PMID- 9978400 TI - Absorption spectroscopic measurements of plume density and temperature in production of nanocrystalline NbAl3 by laser ablation deposition. PMID- 9978401 TI - Roughening transitions of driven surface growth. PMID- 9978402 TI - Structural, electronic, and vibrational properties of diamond (100), (111), and (110) surfaces from ab initio calculations. PMID- 9978403 TI - Width of the plasmon resonance in metal clusters. PMID- 9978404 TI - Metal-insulator transition in the two-band Hubbard model. PMID- 9978405 TI - Symmetric stress tensor in the local-density-functional framework using a separable nonlocal pseudopotential. PMID- 9978406 TI - Efficient quasiparticle band-structure calculations for cubic and noncubic crystals. PMID- 9978407 TI - Electronic and structural properties of cubic BN and BP. PMID- 9978408 TI - Comparative spectroscopic studies of Cs- and K-doped polyacetylene. PMID- 9978409 TI - Coherent oscillations in semiconductor microcavities. PMID- 9978410 TI - Annealing effect on native-oxide/Si(111) interfaces studied by second-harmonic generation. PMID- 9978412 TI - Skyrmions in higher Landau levels. PMID- 9978411 TI - Reconstruction of the GaAs (311)A surface. PMID- 9978413 TI - Experimental determination of the quasiparticle charge and the energy gap in the fractional quantum Hall effect. PMID- 9978415 TI - Proposed magnetoinductance measurements in the quantum-Hall-effect regime: Current distribution in edge channels. PMID- 9978414 TI - Entangled electronic states in multiple-quantum-dot systems. PMID- 9978416 TI - Quantum-conductance-fluctuation correlation range and amplitude as a parameter independent probe of the localized-to-extended-state transition in narrow Si MOSFET's. PMID- 9978417 TI - Spatially indirect transitions due to coupling between a hole accumulation layer and a quantum well in resonant-tunneling diodes. PMID- 9978418 TI - Surface core-level shifts on Nb(001). PMID- 9978419 TI - Thermal diffuse scattering from surface-melted Pb(110). PMID- 9978420 TI - Comment on "Role played by N and N-N impurities in type-IV semiconductors" PMID- 9978421 TI - Nearest-neighbor isotopic fine structure of the AsP gap mode in GaP. PMID- 9978422 TI - Structure of negatively charged muonium in n-type GaAs. PMID- 9978423 TI - Structural characterization of (In,Ga)As quantum dots in a GaAs matrix. PMID- 9978424 TI - Effect of spatial dispersion on acoustoelectric current in a high-mobility two dimensional electron gas. PMID- 9978425 TI - Correlation between photoluminescence and density of electronic states in laser deposited porous silicon. PMID- 9978426 TI - Chemical-state-resolved x-ray standing-wave analysis using chemical shift in photoelectron spectra. PMID- 9978427 TI - Suppression of the Kondo effect in quantum dots by even-odd asymmetry. PMID- 9978428 TI - Role of Ge surface segregation in Si/Ge interfacial ordering: Interface formation on a monohydride surface. PMID- 9978429 TI - Importance of the additional step-edge barrier in determining film morphology during epitaxial growth. PMID- 9978430 TI - Metallic conductivity and metal-insulator transition in (AC60)n (A=K, Rb, and Cs) linear polymer fullerides. PMID- 9978432 TI - Further lowering of work function by oxygen adsorption on the K/Si(001) surface. PMID- 9978431 TI - Determination of step-edge barriers to interlayer transport from surface morphology during the initial stages of homoepitaxial growth. PMID- 9978433 TI - Indium-induced lowering of the Schwoebel barrier in the homoepitaxial growth of Cu(100). PMID- 9978435 TI - Photoacoustic-spectra studies on BaX2:Eu2+ (X=F,Cl,Br) phosphors. PMID- 9978434 TI - Crystalline-amorphous transition in silicate perovskites. PMID- 9978436 TI - Enhancement of the electron-irradiation-induced amorphization of Zr2Ni and Zr3Al by hydrogen. PMID- 9978437 TI - X-ray-scattering study of the metal-phthalocyanine-iodine quasi-one-dimensional molecular conductors. PMID- 9978438 TI - Rotational dynamics of solid C70 investigated by the muon-spin-rotation technique. PMID- 9978439 TI - Crossover and scaling in a nearly antiferromagnetic Fermi liquid in two dimensions. PMID- 9978440 TI - Crystal fields of U3+:LaCl3 under pressure. PMID- 9978441 TI - Phase transitions in systems with extremely short-ranged attractions: A density functional theory. PMID- 9978442 TI - Asymptotic behavior of the perturbation expansion in critical dynamics. PMID- 9978444 TI - Orientational and translational disorder in semiconducting Zintl compounds. PMID- 9978443 TI - Bonding nature in tellurite glasses. PMID- 9978446 TI - Probability of return to the origin at short times: A probe of microstructure in porous media. PMID- 9978445 TI - Defect formation and evolution in TeO2-containing borosilicate glass films derived from a sol-gel process. PMID- 9978447 TI - Theory of the energy spectrum of excess electrons in highly polarizable fluids. PMID- 9978449 TI - Dense quasiperiodic decagonal disc packing. PMID- 9978448 TI - Random-phase calculations of frequency-dependent polarizabilities and hyperpolarizabilities of long polyene chains. PMID- 9978451 TI - Dynamical diffraction in quasicrystals. PMID- 9978450 TI - Embedded-atom model of glass-forming Si-metal alloys. PMID- 9978452 TI - Resonance Raman scattering in Cr4+-doped forsterite. PMID- 9978453 TI - Excitations, order parameters, and phase diagram of solid deuterium at megabar pressures. PMID- 9978454 TI - Vibrational spectroscopy and soft-mode behavior in Rochelle salt. PMID- 9978456 TI - Fast domain growth through density-dependent diffusion in a driven lattice gas. PMID- 9978455 TI - Asymptotic expansions in the path-integral approach to the bipolaron problem. PMID- 9978457 TI - Theory of phonon-phonon interaction in anharmonic crystals with randomly distributed isotopic impurities. PMID- 9978458 TI - Electron-phonon interaction, localization, and polaron formation in one dimensional systems. PMID- 9978460 TI - Antiferromagnetic domain walls. PMID- 9978459 TI - Resistivity, magnetization, and specific heat of YbAgCu4 in high magnetic fields. PMID- 9978461 TI - Multiple wave-vector extensions of the NMR pulsed-field-gradient spin-echo diffusion measurement. PMID- 9978462 TI - Microwave-envelope soliton threshold powers and soliton numbers. PMID- 9978464 TI - Magnetoelastic properties and level crossing in HoVO4. PMID- 9978463 TI - Subsidiary-absorption spin-wave-instability processes in yttrium iron garnet thin films: Coupled lateral standing modes, critical modes, and the kink effect. PMID- 9978465 TI - Magnetic phase diagram, static properties, and relaxation of the insulating spin glass CoCl2 PMID- 9978466 TI - First-principles calculations of the electronic structure and magnetic properties of 3d transition-metal impurities in bcc and amorphous iron. PMID- 9978467 TI - Crystal-electric-field interaction in R2Zn17 intermetallics. PMID- 9978468 TI - Effects of temperature and hydrostatic pressure on the magnetoelasticity of a commensurate spin-density-wave antiferromagnetic Cr-3.5 at. % Al alloy single crystal. PMID- 9978470 TI - Dissipation and interference effects in macroscopic magnetization tunneling and coherence. PMID- 9978469 TI - Coupling between magnetized layers. PMID- 9978471 TI - Simultaneous determination of Fe 3p spin-orbit and exchange splittings in photoemission. PMID- 9978472 TI - Spin-wave resonance and magnetic properties in amorphous Co95-xZr5Mx (M=Zr,Nb,Ti) and Co91-xZr9Ptx thin films. PMID- 9978473 TI - Domain growth in the three-dimensional random-field Ising magnet Fe0.5Zn0.5F2. PMID- 9978474 TI - Muon-spin-relaxation study of magnetic order in RNiO3 (R=rare earth) below the metal-insulator transition. PMID- 9978475 TI - Thermomagnetics of reversible transverse susceptibility. PMID- 9978476 TI - Axial anisotropy of Co2+ in CdSe from the magnetization step and EPR. PMID- 9978477 TI - Renormalization of the anisotropic linear XY model. PMID- 9978478 TI - Phase transitions in ferromagnets with dipolar interactions and uniaxial anisotropy. PMID- 9978479 TI - Calculations of the ferromagnet-to-spin-glass transition in diluted magnetic systems with an RKKY interaction. PMID- 9978481 TI - Superconducting fluctuations in one-dimensional multiband models. PMID- 9978480 TI - Critical behavior of a frustrated spin-1 Ising model. PMID- 9978482 TI - Specific heat of thin 3He films on a disordering substrate. PMID- 9978484 TI - Collective modes with a sound spectrum in layered superconductors. PMID- 9978483 TI - Scaling of thin-film Nd1.85Ce0.15CuO4-y resistivity-current isotherms at low fields: Implications for vortex phase transitions and universality. PMID- 9978486 TI - Current-voltage characteristics of two-dimensional vortex-glass models. PMID- 9978485 TI - Flux-flow Hall effect in clean type-II superconductors. PMID- 9978487 TI - Andreev spectroscopy of Josephson coupling. PMID- 9978488 TI - Gap-function anisotropy and collective modes in a bilayer superconductor with Cooper-pair tunneling. PMID- 9978489 TI - Linear response of thin superconductors in perpendicular magnetic fields: An asymptotic analysis. PMID- 9978490 TI - Vortex-induced strain and flux lattices in anisotropic superconductors. PMID- 9978491 TI - Quantum vortex fluid in two dimensions. PMID- 9978492 TI - Observation of vortex-lattice melting by NMR spin-lattice relaxation in the mixed state. PMID- 9978493 TI - Failure of hydrodynamics within the vortex-liquid phase. PMID- 9978494 TI - Phonon squeezing via correlations in the superconducting electron-phonon interaction. PMID- 9978495 TI - Wetting of 3He-4He mixtures on cesium and other alkali metals. PMID- 9978496 TI - Defect model for nonstoichiometry in YBa2Cu3O6+y. PMID- 9978497 TI - Transverse magnetoresistance of YBa2Cu3Ox single crystals with different oxygen content. PMID- 9978498 TI - Susceptibility and Knight-shift anomalies in cuprate superconductors. PMID- 9978499 TI - Charge transfer and superconductor-metal-insulator transitions in high-Tc superconductors. PMID- 9978500 TI - Structure and superconductivity of HgBa2Ca2Cu3O8+ delta. PMID- 9978501 TI - Unusual insulating phase at low temperature in thin indium films. PMID- 9978502 TI - Evidence for nonuniversal behavior of paraconductivity caused by predominant short-wavelength Gaussian fluctuations in YBa2Cu3O6.9. PMID- 9978503 TI - Effects of oxygen on the magnetic order of the rare-earth ions in RBa2Cu3O6+x (R=Dy, Er, Nd). PMID- 9978504 TI - Critical sheet resistance and two-dimensional properties of Bi2Sr2CuOx thin films. PMID- 9978506 TI - Mechanisms of heat conductivity in high-Tc superconductors. PMID- 9978505 TI - Limits to the critical transport current in superconducting (Bi,Pb)2Sr2Ca2Cu3O10 silver-sheathed tapes: The railway-switch model. PMID- 9978507 TI - Spin pseudogap and interplane coupling in Y2Ba4Cu7O15: A 63Cu nuclear spin-spin relaxation study. PMID- 9978509 TI - Vortex dynamics in a Bi2Sr2CaCu2O8 crystal with columnar defects. PMID- 9978508 TI - Observation of current strings in Bi2Sr2CaCu2O8 single crystals. PMID- 9978510 TI - Laser heating of YBa2Cu3O7 films in Raman experiments. PMID- 9978511 TI - Dynamic susceptibility and photoemission in the t-t'-J model. PMID- 9978512 TI - Magnetism and pairing in Hubbard bilayers. PMID- 9978513 TI - Impurity-induced virtual bound states in d-wave superconductors. PMID- 9978514 TI - Negative pressure effects in high-pressure oxygen-intercalated C60. PMID- 9978516 TI - Molecular-dynamics method for simulating heterogeneous condensed matter at constant pressure. PMID- 9978515 TI - Changes in structure and electronic state from C60 fullerene to amorphous diamond. PMID- 9978518 TI - Free-electron-like Hall effect and deviations from free-electron behavior in Ca Al amorphous alloys. PMID- 9978517 TI - Enhanced inelastic backscattering of electrons from disordered media. PMID- 9978519 TI - Inhomogeneity of the spatial distribution of vibrational modes in a computer model of amorphous argon. PMID- 9978520 TI - Effects of defects on the friction between film and substrate in a microbalance experiment. PMID- 9978521 TI - Anomalous dependence of the o-D2 roton linewidth on the p-D2 concentration in (p D2)x(o-D2)1-x mixed crystals. PMID- 9978522 TI - Hyperfine structure of Gd3+ in Bi2Te3 from EPR. PMID- 9978523 TI - Dynamical scaling in ferric oxide spin glasses. PMID- 9978524 TI - Generalized susceptibility and magnetic ordering in rare-earth nickel boride carbides. PMID- 9978525 TI - Nonmagnetic impurity in the spin-gap state. PMID- 9978526 TI - Escape-field distribution for escape from a metastable potential well subject to a steadily increasing bias field. PMID- 9978527 TI - Observation of Cu2+ spin resonance in Gd2CuO4. PMID- 9978529 TI - Violation of Anderson's theorem for superconductors with nonretarded interactions. PMID- 9978528 TI - Pancake vortex in a superconducting cylinder. PMID- 9978530 TI - Relationship between the roton minimum and T lambda in 4He. PMID- 9978531 TI - Problems with the vortex-boson mapping in 1+1 dimensions. PMID- 9978532 TI - Relaxation towards phase-locked dynamics in long Josephson junctions. PMID- 9978533 TI - Relationship between planar-copper-apical-oxygen bond length and charge transfer in YBa2Cu3O7- delta superconductors. PMID- 9978534 TI - Coexistence of metallic and nonmetallic charge transport in PrBa2Cu3O7. PMID- 9978536 TI - Electronic Raman scattering across the unconventional charge gap in FeSi. PMID- 9978535 TI - High-precision calculation of crystallographic phase-transition pressures for aluminum. PMID- 9978537 TI - Phase transitions in the symmetric Kondo-lattice model in two and three dimensions. PMID- 9978539 TI - Riser fluctuations and vortices at Shapiro steps in Josephson-junction arrays. PMID- 9978538 TI - Penetration-depth anisotropy in unconventional superconductors. PMID- 9978541 TI - Scaling behavior of the magnetic-field-tuned superconductor-insulator transition in two-dimensional Josephson-junction arrays. PMID- 9978540 TI - Brinkman-Rice transition driven by interatomic repulsion in hexagonal copper oxides. PMID- 9978542 TI - Generation of ultrasonic waves by ac magnetic fields in the mixed state of high Tc superconductors. PMID- 9978543 TI - Transport properties of zinc-doped YBa2Cu3O7- delta thin films. PMID- 9978544 TI - Electronic structure of HgBa2CaCu2O6+ delta epitaxial films measured by x-ray photoemission. PMID- 9978545 TI - Erratum: Surface and bulk magnetostatic modes in a ferromagnetic/nonmagnetic superlattice PMID- 9978546 TI - Computationally efficient representation for elastostatic and elastodynamic Green's functions for anisotropic solids. PMID- 9978547 TI - Melting temperature of Na from linear-response-theory molecular dynamics. PMID- 9978548 TI - Ion-beam-induced transformation of diamond. PMID- 9978549 TI - Phase transitions in CdTe to 28 GPa. PMID- 9978550 TI - Solid-solid interface and solid solution of oxides with rock-salt structure: Lattice properties. PMID- 9978551 TI - Phase transitions of the striped domain-wall phases of S on Ru(0001). PMID- 9978552 TI - Effect of pressure on energy levels of Sm2+ in BaFCl and SrFCl. PMID- 9978553 TI - Excitonic energy transfer in Au-doped and undoped Kr solids. PMID- 9978555 TI - Simple phenomenological approach to premelting and sublattice melting in Frenkel disordered ionic crystals. PMID- 9978554 TI - Defect structure of ferrous oxide Fe1-xO. PMID- 9978556 TI - Electronic stopping of heavy ions in the Kaneko model. PMID- 9978557 TI - Nonempirical phase equilibria in the W-Mo-Cr system. PMID- 9978559 TI - Identification of spatially confined states in two-dimensional quasiperiodic lattices. PMID- 9978558 TI - Density of states of electrons in liquid lithium. PMID- 9978560 TI - Nucleation of quasicrystals by rapid cooling of a binary melt: A molecular dynamics study. PMID- 9978561 TI - Effects of interaction-potential nonlinearities and restoring-force anharmonicities in the discrete nonlinear Schrodinger equation. PMID- 9978562 TI - Gauss procedure for the construction of self-localized solitons in discrete systems. PMID- 9978563 TI - Recovery of an N-body potential from a universal cohesion equation. PMID- 9978564 TI - Temperature dependence of acoustic attenuation in silicon. PMID- 9978565 TI - Determination of the fluorine-fluorine potential in fluoroperovskites and prediction of phonon dispersion curves. PMID- 9978566 TI - Structure and dynamics of two-dimensional lattices in random pinning potentials. PMID- 9978567 TI - Quantum diffusion of muonium in the alkali halides. PMID- 9978569 TI - Theory of Raman light scattering in the many-sublattice exchange-noncollinear magnets UO2, RMnO3, and Nd2CuO4 (R=rare-earth ion). PMID- 9978568 TI - Exchange frustration and transverse spin freezing in iron-rich metallic glasses. PMID- 9978570 TI - Real-space density-matrix renormalization-group study of the Kondo necklace. PMID- 9978571 TI - Definition and measurement of the surface magnetoelastic coupling coefficients in thin films and multilayers. PMID- 9978572 TI - Epitaxial strain and magnetic anisotropy in ultrathin Co films on W(110). PMID- 9978573 TI - Disorder-induced optical and paramagnetic properties in zirconium dioxide: Role of low-symmetry crystal fields. PMID- 9978574 TI - Constant-magnetic-field effect in Neel relaxation of single-domain ferromagnetic particles. PMID- 9978575 TI - Effects of spin-dependent spectral weight on magnetic circular x-ray dichroism: Applications to R(NixCo1-x)5 intermetallic compounds. PMID- 9978576 TI - Anisotropy and orientational dependence of magnetization reversal processes in epitaxial ferromagnetic thin films. PMID- 9978577 TI - Quantum fluctuations of solitons in two-dimensional anisotropic sigma models. PMID- 9978578 TI - Nuclear magnetic relaxation and electron-spin fluctuation in a triangular-lattice Heisenberg antiferromagnet CsNiBr3. PMID- 9978579 TI - Energy-gap suppression in heavy-fermion semiconductors by nonmagnetic impurities. PMID- 9978581 TI - Brillouin-zone mapping of the existence conditions for interface bilayer spin waves. PMID- 9978580 TI - Perturbed-angular-correlation study of static and dynamic quadrupole interactions in the Laves-phase hydrides HfV2Hx. PMID- 9978582 TI - Spin dynamics in the amorphous antiferromagnet Si:P. PMID- 9978583 TI - Metamagnetism in the Cr2V4-xMoxO13+0.5x solid solutions. PMID- 9978584 TI - Magnetization reversal process of Zn-bonded anisotropic Sm-Fe-N permanent magnets. PMID- 9978585 TI - Striped phases in two-dimensional dipolar ferromagnets. PMID- 9978586 TI - Simulated-annealing method for fermion systems at finite temperature. PMID- 9978587 TI - Electron transport in magnetic inhomogeneous media. PMID- 9978588 TI - Trigonal interactions in holmium. PMID- 9978589 TI - Spin diffusion of the t-J model. PMID- 9978590 TI - Anderson-Yuval approach to the multichannel Kondo problem. PMID- 9978592 TI - Low-temperature properties of a spin-1 antiferromagnetic chain. PMID- 9978591 TI - Magnetic susceptibility in the spin-Peierls system CuGeO3. PMID- 9978594 TI - Impurities in s=1 Heisenberg antiferromagnets. PMID- 9978593 TI - Reorientation transitions of first and second order in thin ferromagnetic films. PMID- 9978595 TI - Elementary excitations of S=1 antiferromagnetic Heisenberg chains with bond alternation. PMID- 9978597 TI - Critical behavior of the uniform susceptibility of a Fermi liquid near an antiferromagnetic transition with dynamic exponent z=2. PMID- 9978596 TI - Low-energy and dynamical properties of a single hole in the t-Jz model. PMID- 9978598 TI - Electronic structure of RNi2B2C (R=rare earth) from x-ray-absorption spectroscopy. PMID- 9978600 TI - Raman-active intramolecular CH2 and C=C vibrations and microwave surface impedance studies of the organic superconductor kappa - PMID- 9978599 TI - High-angle grain-boundary junctions in YBa2Cu3O7: Normal-state resistance and 1/f noise. PMID- 9978601 TI - Appearance of vortices in rotating He II. PMID- 9978602 TI - Influence of inelastic effects on differential conductance of a high-Tc superconductor/metal junction. PMID- 9978603 TI - Observation of low-lying levels in UBe13. PMID- 9978605 TI - Low-magnetic-field critical behavior in strongly type-II superconductors. PMID- 9978604 TI - Computational simulation of type-II superconductivity including pinning phenomena. PMID- 9978606 TI - Phase transition in the XY gauge glass. PMID- 9978608 TI - Relevance of interchain pair hopping in correlated Hubbard chains. PMID- 9978607 TI - Electron microscopy investigation of iodine intercalated in Bi2Sr2CaCu2Ox: Location and ordering of I3- molecules. PMID- 9978610 TI - Surface and size effect of a dxy-state superconductor. PMID- 9978609 TI - Nonlinear Meissner effect in unconventional superconductors. PMID- 9978611 TI - Matrix model approach to the flux-lattice melting in two-dimensional superconductors. PMID- 9978613 TI - Twin-boundary pinning of superconducting vortex arrays. PMID- 9978612 TI - Thin-film anisotropic transport measurement on tilted Bi2Sr2CaCu2Ox. PMID- 9978614 TI - Flux quantization in weak links in melt-textured bulk YBa2Cu3O7-x. PMID- 9978615 TI - Effects of magnetic history on the ac magnetic susceptibility of granular YBa2Cu3O7- delta superconductors in weak fields. PMID- 9978616 TI - Superconductivity in the two-dimensional Hubbard model: One-particle correlation functions. PMID- 9978617 TI - Superconducting ground state in a model with bond-charge interaction. PMID- 9978618 TI - Electronic Raman scattering in superconductors as a probe of anisotropic electron pairing. PMID- 9978619 TI - Critical-current anisotropy due to inclined and crossed linear defects. PMID- 9978620 TI - Penetration-depth calculations in the ab and c directions in a layered S/N superconductor. PMID- 9978621 TI - Bloch-Gruneisen behavior for the in-plane resistivity of Bi2Sr2CuOx single crystals. PMID- 9978622 TI - Nuclear resonant scattering of synchrotron radiation by gaseous krypton. PMID- 9978623 TI - Composition dependence of the ferroelectric-paraelectric transition in the mixed system PbZr1-xTixO3. PMID- 9978624 TI - Structure and stability of several high-pressure crystalline polymorphs of silica. PMID- 9978625 TI - dc conductivity of molybdenum tellurite glasses. PMID- 9978626 TI - Statistics of fluctuations for two types of crossover: From the ballistic to diffusive regime and from the orthogonal to unitary ensemble. PMID- 9978627 TI - Spatial distribution of defects in LiF induced by low-energy electron bombardment: Evidence for rapid hot-hole diffusion. PMID- 9978628 TI - Absence of acoustic signature of the quadrupolar Kondo effect in U0.2Y0.8Pd3. PMID- 9978630 TI - Phase transition in the spatially anisotropic classical XY model. PMID- 9978629 TI - Occasional appearance of antiferromagnetism in mainly ferromagnetic samples of UCu2Si2. PMID- 9978631 TI - Scaling law for a magnetic impurity model with two-body hybridization. PMID- 9978632 TI - Spin-wave interaction effects in the Neel phase of the J1-J2-J3 model. PMID- 9978633 TI - Magnetoelectric effect in fibrous composites with piezoelectric and piezomagnetic phases. PMID- 9978634 TI - Intrinsic magnetic resonance in superparamagnetic systems. PMID- 9978635 TI - High- and low-spin transition of Ru4+ in the perovskite-related layered system Srn+1RunO3n+1 (n=1, 2, and PMID- 9978636 TI - Superconducting and calorimetric properties of the quaternary borocarbide superconductor LaPd2B2C. PMID- 9978637 TI - Symmetry of trapped-field profiles in square columnar Josephson-junction arrays. PMID- 9978638 TI - Superconductivity in Y0.6Pr0.4Ba2-xSrxCu3O7- delta : The role of apical oxygen in hybridization. PMID- 9978639 TI - Critical scaling of third-harmonic transmissivity near the Bose-glass transition in YBa2Cu3O7 single crystals with columnar defects. PMID- 9978640 TI - Superconducting transition temperatures from anisotropic interactions. PMID- 9978641 TI - Singlet stripe phases in the planar t-J model. PMID- 9978643 TI - Comment on "Structures of sodium metal" PMID- 9978642 TI - Raman study of the copper isotope effect in YBa2Cu3O7- delta. PMID- 9978644 TI - Reply to "Comment on 'Structures of sodium metal' " PMID- 9978645 TI - Comment on "Perimeter-maximum-diameter method for measuring the fractal dimension of a fractured surface" PMID- 9978646 TI - Phase separation and phase transitions in KC60: A 13C NMR study. PMID- 9978648 TI - Significant enhancement of optical nonlinearity by quantum lattice fluctuations in pi -conjugated polymers. PMID- 9978647 TI - Role of the interface in ion-induced alloy phase formation in an immiscible Y-Ta system. PMID- 9978650 TI - Observation of a possible oxygen isotope effect on the effective mass of carriers in YBa2Cu3O6.94. PMID- 9978649 TI - Quantum critical behavior in a two-layer antiferromagnet. PMID- 9978651 TI - Pressure effect on the double-exchange ferromagnet La1-xSrxMnO3 (0.15 <= x <= 0.5). PMID- 9978653 TI - Superconducting phases of La2CuO4+ delta prepared by electrochemical oxidation at ambient temperature. PMID- 9978652 TI - Phonon structure in the tunneling conductance of Bi2Sr2CaCu2O8. PMID- 9978654 TI - 89Y NMR study of the effect of Zn substitution on the spin dynamics of YBa2Cu4O8. PMID- 9978655 TI - Optical properties of radiation defect centers involving single and paired Mn2+ centers in CaF2:Mn. PMID- 9978656 TI - Magnetic correlations on the insulating side of the metal-insulator transition in amorphous Si1-xMnx. PMID- 9978657 TI - Electron correlation and dimerization in trans-polyacetylene: Many-body perturbation theory versus density-functional methods. PMID- 9978658 TI - Nonlinearities in bismuth under supersonic electron drift. PMID- 9978659 TI - Density-functional description of the electronic structure of LaMO3 (M=Sc,Ti,V,Cr,Mn,Fe,Co,Ni). PMID- 9978660 TI - Hole-polaron formation in the two-dimensional Holstein t-J model: A variational Lanczos study. PMID- 9978661 TI - Breakdown of the quasiparticle picture in the low-density limit of the one dimensional Hubbard model. PMID- 9978662 TI - Two-band singlet-hole model for the copper oxide plane. PMID- 9978663 TI - Analysis of separable nonlocal pseudopotentials. PMID- 9978664 TI - Effects of orientational disorder on the electronic structure and transport in AxC70. PMID- 9978666 TI - Alternative local approach to nonorthogonal tight-binding theory: Environment dependence of the interaction parameters in an orthogonal basis. PMID- 9978665 TI - Constraints on pairings in the Hubbard model. PMID- 9978667 TI - Order-N spectral method for electromagnetic waves. PMID- 9978669 TI - Excitonic optical nonlinearities and transport in the layered compound semiconductor GaSe. PMID- 9978668 TI - Optical spectroscopy of Pr3+ ions in LiNbO3. PMID- 9978670 TI - Raman-scattering probe of anharmonic effects in GaAs. PMID- 9978671 TI - Space-charge-limited photocurrent transients: The influence of bimolecular recombination. PMID- 9978672 TI - Intrinsic radiative lifetimes of donor-acceptor pair excitations in diamond. PMID- 9978674 TI - Optical absorption of free small polarons at high temperatures. PMID- 9978673 TI - Silicon defects in diamond. PMID- 9978675 TI - k PMID- 9978677 TI - Polarization dependence of the frequency-domain four-wave-mixing response of excitons in GaAs. PMID- 9978678 TI - Electronic states associated with dislocations in p-type silicon studied by means of electric-dipole spin resonance and deep-level transient spectroscopy. PMID- 9978676 TI - High-field hopping transport in band tails of disordered semiconductors. PMID- 9978679 TI - Improved hydrodynamical model for carrier transport in semiconductors. PMID- 9978680 TI - Optical detection of magnetic resonance of nitrogen and nickel in high-pressure synthetic diamond. PMID- 9978681 TI - Electron-paramagnetic-resonance identification of hydrogen-passivated sulfur centers in silicon. PMID- 9978682 TI - High-pressure effects in the layered semiconductor germanium selenide. PMID- 9978683 TI - Path-integral Monte Carlo simulation of hydrogen in crystalline silicon. PMID- 9978685 TI - Pressure-induced Hall-effect spectroscopy of silicon DX states in planar doped GaAs-AlAs superlattices. PMID- 9978684 TI - Tight-binding model and interactions scaling laws for silicon and germanium. PMID- 9978686 TI - Phonon broadening of excitons in GaAs/AlxGa1-xAs quantum wells. PMID- 9978688 TI - Interface luminescence of GaAs/Ga1-xAlxAs heterostructures: Threshold effect of the interface formation conditions. PMID- 9978689 TI - Conductance fluctuations in mesoscopic three-dimensional multiply connected normal-wire networks. PMID- 9978687 TI - Well-width dependence of the optical anisotropies in (001) and (110) semiconductor quantum wells: The effect of spin-orbit split-off bands. PMID- 9978691 TI - Overlayer growth and electronic properties of the Bi/GaSb(110) interface. PMID- 9978690 TI - Germanium 70Ge/74Ge isotope heterostructures: An approach to self-diffusion studies. PMID- 9978692 TI - Nonlinear I(V) characteristics of Luttinger liquids and gated Hall bars. PMID- 9978693 TI - Characteristics of the conductance of a quantum waveguide containing an array of stubs: Numerical simulation. PMID- 9978694 TI - Grazing-incidence diffraction from multilayers. PMID- 9978695 TI - Carrier-carrier scattering in photoexcited intrinsic GaAs quantum wells and its effect on femtosecond plasma thermalization. PMID- 9978696 TI - Semiclassical theory of shot-noise suppression. PMID- 9978698 TI - Generalized circular ensemble of scattering matrices for a chaotic cavity with nonideal leads. PMID- 9978699 TI - Fano resonances in the optical spectra of semiconductor quantum structures. PMID- 9978697 TI - Coulomb gap in a two-dimensional electron gas with a close metallic electrode. PMID- 9978701 TI - Electron-electron scattering in a two-dimensional electron gas in a strong magnetic field. PMID- 9978700 TI - (001)-surface-induced bulk states and surface resonances in II-VI zinc-blende semiconductors. PMID- 9978702 TI - Wetting of monovalent metals on semiconductors and insulators. PMID- 9978703 TI - Random-matrix theory and the cumulants of the conductance for quasi-one dimensional mesoscopic systems. PMID- 9978704 TI - Conduction-band spin splitting and negative magnetoresistance in A3B5 heterostructures. PMID- 9978705 TI - Andreev resonances in the current-voltage characteristics of a normal-metal superconductor junction. PMID- 9978706 TI - Ultrafast carrier relaxation and vertical-transport phenomena in semiconductor superlattices: A Monte Carlo analysis. PMID- 9978707 TI - Elementary excitations and off-diagonal long-range order in double-layer quantum Hall systems. PMID- 9978708 TI - Ultrafast edge photoexcitation and coherent oscillations in tunnel-coupled double quantum wells. PMID- 9978709 TI - Reflectivity of the quantum grating and the grating polariton. PMID- 9978711 TI - Shape resonances in photoemission for CO molecules adsorbed on metallic surfaces: A model including backscattering. PMID- 9978710 TI - Impurity necklaces in the two-dimensional electron gas. PMID- 9978713 TI - Phase transitions of argon multilayer films on graphite: Evolution from multilayer film to bulk solid. PMID- 9978712 TI - Adsorption of sodium and potassium on a gold(100) surface: An example of alkali metal-induced deconstruction. PMID- 9978714 TI - Orientational disorder in C60 below Ts: A diffuse-neutron-scattering study. PMID- 9978716 TI - Capillary phenomena in extremely thin zeolite channels and metal-dielectric interaction. PMID- 9978715 TI - Two-dimensional electron-scattering processes on Na-dosed Cu(111): A two-photon photoemission study. PMID- 9978717 TI - Structure and dynamics of the reconstructed Au(511) surface. PMID- 9978719 TI - Charge transfer, doping, and interface morphologies for Al-C60. PMID- 9978718 TI - Full structure determination of an alkali-metal/CO coadsorption phase for Co{101 bar0}-c(2 x 2)-(K+CO). PMID- 9978721 TI - Epitaxial lines and the metastability of bcc cobalt. PMID- 9978720 TI - Determination of electrophysical properties of a layered structure with a statistically rough surface via an inversion method. PMID- 9978722 TI - Electronic structure and scanning-tunneling-microscopy image of molybdenum dichalcogenide surfaces. PMID- 9978724 TI - Transmission of electromagnetic waves through thin metal films with randomly rough surfaces. PMID- 9978723 TI - Intermixing at Au-In interfaces as studied by photoelectron spectroscopy. PMID- 9978725 TI - Transport in channels and films with rough surfaces. PMID- 9978727 TI - Electronic structure, surface states, surface energy, and work function of the Cu(100) surface. PMID- 9978726 TI - Predicted c(2 x 2) buckling reconstruction of monolayer Mn on Fe(001) and its importance to the interfacial magnetic ordering. PMID- 9978728 TI - Equilibrium structure and migration of a single dimer vacancy on the Si(001) surface. PMID- 9978729 TI - Frenkel-Kontorova model with a nonconvex transverse degree of freedom: A model for reconstructive surface growth. PMID- 9978730 TI - Core-level shifts in bulk alloys and surface adlayers. PMID- 9978732 TI - Mechanism for the metal-insulator transition in Sr2Ir1-xRuxO4. PMID- 9978731 TI - Reality of the eigenfrequencies of periodic elastic composites. PMID- 9978733 TI - Carbon- and oxygen-related point defects created by annealing the dicarbon radiation-damage center in crystalline silicon. PMID- 9978735 TI - Dielectric scaling of the self-energy scissor operator in semiconductors and insulators. PMID- 9978734 TI - Electronic and elastic properties of edge dislocations in Si. PMID- 9978736 TI - Hole refraction from strained Si1-xGex/Si heterostructures. PMID- 9978737 TI - Exciton states in the GaAs/Ga1-xAlxAs corrugated superlattices grown on (311) oriented substrates. PMID- 9978738 TI - Effects of hydrogen impurities on the diffusion, nucleation, and growth of Si on Si(001). PMID- 9978740 TI - Fermi level of low-temperature-grown GaAs on Si- delta -doped GaAs. PMID- 9978739 TI - Selection rules in Raman scattering by plasmons in quantum wires. PMID- 9978741 TI - Fano resonances in transport across a quantum well in a tilted magnetic field. PMID- 9978742 TI - Conductance distribution in quantum dots with point contacts. PMID- 9978743 TI - Destruction of the quantum Hall effect with increasing disorder. PMID- 9978745 TI - Lateral size effects on cells in ferroelectric films. PMID- 9978744 TI - Observation of induced dipoles between small palladium clusters and alpha -(0001) Al2O3. PMID- 9978746 TI - Scaling of level statistics at the disorder-induced metal-insulator transition. PMID- 9978747 TI - Magnetothermopower oscillations in a lateral superlattice. PMID- 9978748 TI - Charged pseudospin textures in double-layer quantum Hall systems with spontaneous interlayer coherence. PMID- 9978749 TI - Schottky contacts on a highly doped organic semiconductor. PMID- 9978750 TI - Native defects in gallium nitride. PMID- 9978751 TI - Composite fermions traversing a potential barrier. PMID- 9978752 TI - Homogeneous linewidths of excitons in CdTe/(Cd,Zn)Te single quantum wells. PMID- 9978754 TI - Investigation of miniband formation in a graded-gap superlattice by electroreflectance spectroscopy. PMID- 9978753 TI - Resonant coupling of electrons and excitons in an aperiodic superlattice under electric fields studied by photoluminescence spectroscopy. PMID- 9978755 TI - Bloch oscillations at room temperature. PMID- 9978756 TI - Collective transport in two-dimensional magnetic bubble arrays. PMID- 9978757 TI - Advacancy-induced step bunching on vicinal surfaces. PMID- 9978759 TI - Near-infrared emission of Cr4+-doped garnets: Lifetimes, quantum efficiencies, and emission cross sections. PMID- 9978758 TI - Erratum: Magnetoresistance of a two-dimensional electron gas in a random magnetic field PMID- 9978760 TI - Model of electron-proton correlation in quasi-one-dimensional halogen-bridged mixed-valence complexes: Role of proton motion. PMID- 9978762 TI - Localization properties of Kronig-Penney incommensurate potentials. PMID- 9978761 TI - Reference force field and charge-density-wave amplitude of mixed-valence halogen bridged Pt complexes. PMID- 9978763 TI - Atomic and electronic structure of icosahedral Al-Pd-Mn alloys and approximant phases. PMID- 9978764 TI - Electronic structure and optical properties of alpha and beta phases of silicon nitride, silicon oxynitride, and with comparison to silicon dioxide. PMID- 9978765 TI - Optical properties and electronic structures of alpha - and gamma -Ce. PMID- 9978766 TI - Local-density-derived semiempirical pseudopotentials. PMID- 9978767 TI - Spin-polarized Hartree-Fock approximation at nonzero temperatures. PMID- 9978768 TI - Elastic constants of hexagonal transition metals: Theory. PMID- 9978769 TI - Model for a strongly correlated insulator: FeSi. PMID- 9978770 TI - Analytical molecular orbitals and band structures of solid C60. PMID- 9978771 TI - Acoustic properties of gallium selenide. PMID- 9978772 TI - Ultrafast thermalization of nonequilibrium holes in p-type tetrahedral semiconductors. PMID- 9978773 TI - Deep-level defects responsible for persistent photoconductivity in Ga-doped Cd1 xMnxTe. PMID- 9978774 TI - Cu L3 core-hole effects in the x-ray absorption of CuCl. PMID- 9978775 TI - ac conductivity of glassy Bi4-nPbnSr3Ca3Cu4Ox semiconductors (with n=0.0, 0.1, 0.5, and 1.0): Precursors for high-Tc superconductors. PMID- 9978776 TI - Electronic and transformation properties of a metastable defect introduced in n type GaAs by alpha -particle irradiation. PMID- 9978778 TI - Band gap of porous silicon. PMID- 9978777 TI - Temperature dependence of photoluminescence in porous silicon and its interpretation using the porous-cluster model. PMID- 9978779 TI - Frenkel pairs in low-temperature electron-irradiated InP: Optical-absorption spectroscopy. PMID- 9978780 TI - Optical investigation of the DX centers in GaAs under hydrostatic pressure. PMID- 9978781 TI - Observation of the nearest-neighbor magnetization step in CdS:Co by Faraday rotation in magnetic fields to 60 T. PMID- 9978782 TI - Chemical and structural studies of disorder and defects in a-GeSe2 films as a function of thermal annealing. PMID- 9978783 TI - Brillouin-scattering measurements of surface-acoustic-wave velocities in silicon at high temperatures. PMID- 9978784 TI - Composite fermions, edge currents, and the fractional quantum Hall effect. PMID- 9978785 TI - Size effects in optical second-harmonic generation by metallic nanocrystals and semiconductor quantum dots: The role of quantum chaotic dynamics. PMID- 9978786 TI - Transition from one- to two-subband occupancy in the 2DEG of back-gated modulation-doped GaAs-AlxGa1-xAs heterostructures. PMID- 9978787 TI - Saturation and voltage quenching of porous-silicon luminescence and the importance of the Auger effect. PMID- 9978788 TI - Vertical transport in GaAs/AlxGa1-xAs superlattices by a microwave time-of-flight technique. PMID- 9978789 TI - Magneto-optics and valence-band discontinuity in a HgTe-Hg1-xCdxTe superlattice. PMID- 9978790 TI - Form of kinetic energy in effective-mass Hamiltonians for heterostructures. PMID- 9978792 TI - Atomic and electronic structure of the Na/Si(111)-(3 x 1) surface. PMID- 9978791 TI - cw photoluminescence determination of thermally activated fast X--> Gamma interlayer electron scattering in type-II GaAs/AlAs superlattices. PMID- 9978793 TI - Tunneling and nonparabolicity effects in in-plane magnetic fields. PMID- 9978794 TI - Cyclotron-resonance studies in relaxed InxGa1-xAs (0 <= x <= 1) epilayers. PMID- 9978795 TI - Interaction of above-Fermi-edge magnetoexciton states from different subbands in dense two-dimensional electron magnetoplasma. PMID- 9978796 TI - Optical measurements of electronic band structure in tensile strain (Ga,In)P (Al,Ga,In)P quantum wells. PMID- 9978798 TI - Depletion layers, plasmon dispersion, and the effects of temperature in degenerate InSb(100): A study by electron-energy-loss spectroscopy. PMID- 9978797 TI - High-resolution x-ray-photoemission study of metastable Fe silicide core-electron states. PMID- 9978799 TI - Electron-interface-phonon interaction and scattering in asymmetric semiconductor quantum-well structures. PMID- 9978800 TI - Field-modulated diffusivity of excitons in coupled asymmetric quantum wells. PMID- 9978801 TI - Spin-orbit interaction, triplet lifetime, and fine-structure splitting of excitons in highly porous silicon. PMID- 9978803 TI - Charge oscillations in double quantum wells: Nonlinear effects caused by the Coulomb interaction. PMID- 9978802 TI - Artificial impurity in interacting electron droplets in a strong magnetic field. PMID- 9978804 TI - Emission of short-wavelength phonons in tunneling through Schottky barriers. PMID- 9978805 TI - Raman scattering due to interface optical phonons in GaAs/AlAs multiple quantum wells. PMID- 9978806 TI - Influence of interfacial atomic structure on the Schottky-barrier height of Si(111)-Pb. PMID- 9978807 TI - Bernstein modes in quantum wires and dots. PMID- 9978809 TI - Thermopower of mesoscopic and disordered systems. PMID- 9978808 TI - Ab initio studies of GaN epitaxial growth on SiC. PMID- 9978810 TI - Theory of quantum-wire formation on corrugated surfaces. PMID- 9978811 TI - Heteroepitaxy of beta -FeSi2 on Si by gas-source MBE. PMID- 9978813 TI - Interfaces, confinement, and resonant Raman scattering in Ge/Si quantum wells. PMID- 9978812 TI - Scanning-tunneling-microscope study of the alpha and beta phases of the GaAs (001)-(2 x 4) reconstruction. PMID- 9978815 TI - Possible bistability of the persistent current of two interacting electrons in a quantum ring. PMID- 9978814 TI - Hole subbands and effective masses in p-doped PMID- 9978816 TI - Tunneling between edge channels and the bulk of a two-dimensional electron gas. PMID- 9978818 TI - Temperature relaxation and the Kapitza-boundary-resistance paradox. PMID- 9978817 TI - Interacting one-dimensional electron gas with open boundaries. PMID- 9978819 TI - Orientational probing of polymeric thin films by NEXAFS: Calculations on polytetrafluoroethylene. PMID- 9978820 TI - Variations of LEED intensities with angle of incidence and the influence on spot profiles. PMID- 9978821 TI - Anisotropy of the stress on fcc(110) surfaces. PMID- 9978822 TI - Inelastic energy loss and charge exchange in low-energy heavy ions scattered from Cu and Cu-alloy surfaces. PMID- 9978823 TI - Reactive crystal growth in two dimensions: Silicon nitride on Si(111). PMID- 9978824 TI - Binding of Li atoms adsorbed on metal surfaces. PMID- 9978825 TI - Phase diagram of the Cu-Pd surface alloy: A first-principles calculation. PMID- 9978826 TI - Near-field microscopy of surface-plasmon polaritons: Localization and internal interface imaging. PMID- 9978828 TI - Quantitative study of the decay of intensity oscillations in transient layer-by layer growth. PMID- 9978827 TI - Temperature- and composition-dependent photoluminescence from the guest ion in intercalated layered aluminosilicate compounds. PMID- 9978829 TI - Surface-structure determination of Sc(0001) using LEED and STM. PMID- 9978830 TI - Structure and stability of Si45 clusters: A generalized tight-binding molecular dynamics approach. PMID- 9978832 TI - Dielectric function and local-field effects of TiSe2. PMID- 9978831 TI - Vacancy island nucleation and inverse growth of InSb(110). PMID- 9978833 TI - Spin-density-wave state of tetramethyltetraselenafulvalinium phosphate (TMTSF)2PF6: Pressure and magnetic-field effects. PMID- 9978835 TI - Photocurrent calculations in beryllium using a local dielectric model. PMID- 9978834 TI - High-resolution photoemission spectroscopy of the Verwey transition in Fe3O4. PMID- 9978836 TI - Electronic structure of insulating Zr3N4 studied by resonant photoemission. PMID- 9978837 TI - Generating tight-binding Hamiltonians with finite-difference methods. PMID- 9978838 TI - Spin-orbit coupling parameters and electron g factor of II-VI zinc-blende materials. PMID- 9978839 TI - Adsorption-state-specific C 1s core-level chemical shifts of thiophene on Si(111)7 x 7 by photoemission spectroscopy at 340 eV. PMID- 9978840 TI - Self-consistent current-voltage characteristics of superconducting nanostructures. PMID- 9978841 TI - Experimental determination of the pressure dependence of the barrier height of metal/ PMID- 9978842 TI - Theory of a type of quantum amplification: Phase-sensitive amplification by frequency upconversion. PMID- 9978843 TI - Cyclotron effective mass of a two-dimensional electron layer at the GaAs/AlxGa1 xAs heterojunction subject to in-plane magnetic fields. PMID- 9978844 TI - Exceptionally slow dephasing of electronic continuum states in a semiconductor. PMID- 9978845 TI - Full-potential total-energy investigation on the lattice relaxation at the two types of NiSi2/Si(111) interface. PMID- 9978846 TI - Phonon scattering on two-dimensional electrons in a high magnetic field. PMID- 9978847 TI - Thermoelectric resonant transport through the Anderson impurities. PMID- 9978849 TI - Disorder-tuned transition between a quantum Hall liquid and Hall insulator. PMID- 9978848 TI - Evidence for quantum states corresponding to families of stable and chaotic classical orbits in a wide potential well. PMID- 9978850 TI - Phase breaking in ballistic quantum dots: Transition from two- to zero dimensional behavior. PMID- 9978852 TI - Influence of metastable states of two-dimensional electrons on the electronic properties of composite fermions. PMID- 9978851 TI - Resonant-energy relaxation of terahertz-driven two-dimensional electron gases. PMID- 9978853 TI - Quenching of excitonic optical transitions by excess electrons in GaAs quantum wells. PMID- 9978854 TI - Low-temperature anti-Stokes luminescence mediated by disorder in semiconductor quantum-well structures. PMID- 9978855 TI - Many-electron theory of Auger surface-ion neutralization. PMID- 9978856 TI - Explanation of the conductivity minimum in tin- and tellurium-doped bismuth. PMID- 9978857 TI - Surface second-harmonic generation from chiral materials. PMID- 9978858 TI - Degenerate ground states of the two-dimensional U= PMID- 9978859 TI - Ab initio total-energy pseudopotential calculations for polymorphic B2O3 crystals. PMID- 9978860 TI - Linear system-size scaling methods for electronic-structure calculations. PMID- 9978861 TI - Electronic structures of transition-metal mono-oxides in the self-interaction corrected local-spin-density approximation. PMID- 9978862 TI - Optical properties of LaSr2Ga11O20 crystals containing Cr3+ PMID- 9978863 TI - Individual versus collective pinning in charge-density-wave systems with impurties. PMID- 9978864 TI - Falicov-Kimball model and the problem of valence and metal-insulator transitions. PMID- 9978865 TI - Cu local density of states in CuAu I from photoemission measurements. PMID- 9978866 TI - Statistics and power spectrum of the electron fluctuations in semiconductors. PMID- 9978867 TI - GW self-energy calculations of carrier-induced band-gap narrowing in n-type silicon. PMID- 9978868 TI - Reactivation kinetics of acceptors in hydrogenated InP during unbiased annealing. PMID- 9978870 TI - Stimulated Brillouin scattering in magnetized direct-gap semiconductors. PMID- 9978869 TI - NMR evidence for the metallic nature of highly conducting polyaniline. PMID- 9978872 TI - Current-voltage characteristics of porous-silicon layers. PMID- 9978871 TI - Analysis of ionized-impurity-scattering relaxation time and mobility by the phase shift method for two interacting valence bands. PMID- 9978873 TI - Boson peak in the Raman spectra of amorphous gallium arsenide: Generalization to amorphous tetrahedral semiconductors. PMID- 9978874 TI - Spin correlations in a two-dimensional electron gas. PMID- 9978875 TI - Nature of bonding of alkali metals to Si(111). PMID- 9978876 TI - Combined theoretical and experimental investigation of the adsorption geometry of Ga on Si(100) at low coverage. PMID- 9978878 TI - Fractional quantum Hall effect on a lattice. PMID- 9978877 TI - Nonradiative processes and luminescence spectra in porous silicon. PMID- 9978880 TI - Derivation of a general expression for the momentum matrix elements within the envelope-function approximation. PMID- 9978879 TI - Electron streaming caused by inelastic acoustic-phonon scattering in quantum wires. PMID- 9978881 TI - Electronic states in one-dimensional polymeric superlattices: A tight-binding approach. PMID- 9978883 TI - Spin-superlattice formation in a type-II ZnSe/Zn0.96Fe0.04Se multiple-quantum well structure. PMID- 9978882 TI - Transient picosecond Raman studies of high-field electron transport in GaAs-based p-i-n nanostructure semiconductors. PMID- 9978884 TI - Phonon properties and Raman response of (113) GaAs/AlAs corrugated superlattices. PMID- 9978885 TI - Simple fit to the ground-state energy of the two-dimensional electron gas in the fractional quantum Hall regime. PMID- 9978886 TI - Visible photoluminescence from nanocrystallite Ge embedded in a glassy SiO2 matrix: Evidence in support of the quantum-confinement mechanism. PMID- 9978888 TI - Theory of one-phonon Raman scattering in semiconductor microcrystallites. PMID- 9978887 TI - Molecular-dynamics study of defect formation in a-Si:H. PMID- 9978889 TI - Self-consistent density of states for heterostructures in strong magnetic fields. PMID- 9978890 TI - Exchange-enhanced spin splitting in a two-dimensional electron system with lateral modulation. PMID- 9978891 TI - Statistical properties of level widths and conductance peaks in a quantum dot. PMID- 9978892 TI - Formation of step structures by As deposition on a double-domain Si(001) substrate. PMID- 9978893 TI - Temperature dependence of the band overlap in InAs/GaSb structures. PMID- 9978894 TI - Theory of resonant tunneling through a quantum wire. PMID- 9978895 TI - Coulomb blockade at almost perfect transmission. PMID- 9978896 TI - Excitation spectrum and collective modes of composite fermions. PMID- 9978897 TI - First-principles study of the electronic and optical properties of confined silicon systems. PMID- 9978898 TI - Correlated few-electron states in vertical double-quantum-dot systems. PMID- 9978899 TI - Anomalous Urbach tail in GaAs. PMID- 9978900 TI - Phonon renormalization effects in photoexcited quantum wires. PMID- 9978901 TI - Low-temperature interface reactions in layered Au/Sb films: In situ investigation of the formation of an amorphous phase. PMID- 9978902 TI - Unoccupied electronic resonances of Sc adsorbed on W(001) by k-resolved inverse photoemission. PMID- 9978903 TI - Conductivity of tridecylmethylammonium-Au(dmit)2 Langmuir-Blodgett films under hydrostatic pressure. PMID- 9978905 TI - Alkali-metal chemisorption on Ta(110). PMID- 9978904 TI - Origin of the extended fine structure in the secondary-electron-emission spectrum of graphite. PMID- 9978906 TI - Alkali-metal-fulleride phase equilibria. PMID- 9978907 TI - Collective resonances in silver clusters: Role of d electrons and the polarization-free surface layer. PMID- 9978909 TI - Linear transport theory of magnetoconductance in metallic multilayers: A real space approach. PMID- 9978908 TI - Initial-state and scattering-factor effects in photoelectron holography. PMID- 9978910 TI - Relation between lattice order and energy-resolved momentum densities in carbon films. PMID- 9978912 TI - Quantum Monte Carlo study of surface diffusion. PMID- 9978911 TI - Periodic orbits and shell structure in octupole deformed potentials. PMID- 9978913 TI - Deformed-jellium model for the fission of multiply charged simple metal clusters. PMID- 9978914 TI - Electronic shell effects in triaxially deformed metal clusters: A systematic interpretation of experimental observations. PMID- 9978915 TI - Fast and versatile method for full-potential total energies: Applications to ordered and disordered alloys. PMID- 9978917 TI - Optical properties of Fe-Rh alloys. PMID- 9978916 TI - Large-U limit of a Hubbard model in a magnetic field: Chiral spin interactions and paramagnetism. PMID- 9978918 TI - Carbon and silicon vacancies in electron-irradiated 6H-SiC. PMID- 9978920 TI - Valence-band offset at AlxGa1-xAs/GaAs: Application of average-bond-energy theory in conjunction with the cluster expansion method. PMID- 9978919 TI - Resonance formalism for the transmission probability of symmetrical multibarrier resonant-tunneling structures. PMID- 9978921 TI - Free-carrier effect on exciton dynamics in GaAs/AlxGa1-xAs quantum wells. PMID- 9978923 TI - Negative-differential band-gap renormalization in type-II GaAs/AlAs superlattices. PMID- 9978922 TI - Photoluminescence study of silicon donors in n-type modulation-doped GaAs/AlAs quantum wells. PMID- 9978924 TI - Ground state of a quantum disk by the effective-index method. PMID- 9978925 TI - STM study of superstructures formed in the Pd/Si(111) system. PMID- 9978926 TI - Kinetics of intermixing in Au/Ag(110) heteroepitaxy: A molecular-dynamics study. PMID- 9978928 TI - Nitrogen adsorption on Rh(110). PMID- 9978927 TI - Resonant second-order Raman spectra of C60 on Ag and In surfaces. PMID- 9978929 TI - Complex surface alloy formed by Li deposition on Cu(001) determined by dynamical low-energy electron diffraction. PMID- 9978931 TI - Structural and electronic properties of C59X (X=B,N): The extended Su-Schrieffer Heeger model. PMID- 9978930 TI - Adsorbate-induced surface expansion: Indicator of the propensity for a structural transformation. PMID- 9978932 TI - Origin of metallic surface core-level shifts. PMID- 9978933 TI - Simulations of polycrystalline growth in 2+1 dimensions. PMID- 9978934 TI - Phonon modes of diamond (100) surfaces from ab initio calculations. PMID- 9978935 TI - Variational wave functions for the Mott transition: The 1/r Hubbard chain. PMID- 9978936 TI - Susceptibility of the one-dimensional dimerized Hubbard model. PMID- 9978937 TI - Luminescence from monolayer-thick Ge quantum wells embedded in Si. PMID- 9978939 TI - X-ray-edge singularity in nonequilibrium systems. PMID- 9978938 TI - Virtual excitation of the Fermi-edge singularity in modulation-doped quantum wells. PMID- 9978940 TI - Quantum conductance fluctuations and classical short-path dynamics. PMID- 9978941 TI - Laughlin-liquid-Wigner-solid transition at high density in wide quantum wells. PMID- 9978942 TI - Scanning-tunneling-microscopy study of surface morphology at the initial growth stage of Si on a 7 x 7 superlattice surface of Si(111). PMID- 9978943 TI - Magnetism of 4d and 5d transition metal adlayers on Ag(001): Dependence on the adlayer thickness. PMID- 9978944 TI - Erratum: Ellipsometric studies of magnetic phase transitions of Fe-Rh alloys PMID- 9978945 TI - Erratum: Valence-band offsets and band tailoring in compound strained-layer superlattices PMID- 9978947 TI - Theoretical studies of vacancies in Al and Cu. PMID- 9978946 TI - Suppression of the metal-to-insulator transition in BaVS3 with pressure. PMID- 9978948 TI - Charge-density-wave glass state in quasi-one-dimensional conductors. PMID- 9978949 TI - Photoemission, x-ray absorption, and inverse-photoemission studies of valence fluctuating Sm3Se4. PMID- 9978950 TI - Density-of-states calculations and multiple-scattering theory for photons. PMID- 9978952 TI - Molecular structure and chemical bonding in K3C60 and K6C60. PMID- 9978951 TI - Numerical implementation of absorbing and injecting boundary conditions for the time-dependent Schrodinger equation. PMID- 9978953 TI - Full-potential band calculations on YTiO3 with a distorted perovskite structure. PMID- 9978955 TI - Structural, electronic, and magnetic properties of 3d transition-metal aluminides with equiatomic composition. PMID- 9978954 TI - Picosecond quantum-beat spectroscopy of quadrupole polaritons in Cu2O. PMID- 9978956 TI - Use of the Ising model in the study of substitutional alloys. PMID- 9978957 TI - Optically detected magnetic-resonance study of a metastable selenium-related center in silicon. PMID- 9978958 TI - Photobleaching of light-induced paramagnetic defects in fast and slow processes in a-Si1-xNx:H alloys. PMID- 9978959 TI - Photoluminescence in a-C:H films. PMID- 9978960 TI - Agglomeration of self-interstitials in Si observed at 450 degreesC by high resolution transmission electron microscopy. PMID- 9978961 TI - Optical and electrical properties of hydrogen-passivated gallium antimonide. PMID- 9978963 TI - Origin of the 4.1-eV luminescence in pure CsI scintillator. PMID- 9978962 TI - Time-convolutionless reduced-density-operator theory of an arbitrary driven system coupled to a stochastic reservoir. II. Optical gain and line-shape function of a driven semiconductor. PMID- 9978964 TI - Observation of slow dangling-bond relaxation in p-type hydrogenated amorphous silicon. PMID- 9978966 TI - Thermal diffusion of a two-layer system. PMID- 9978965 TI - Temperature dependence of carrier relaxation in semiconductor doped glasses. PMID- 9978967 TI - Thermoelectric power of hot carriers in the nonequilibrium-statistical-operator approach. PMID- 9978968 TI - Hopping transport on a fractal: ac conductivity of porous silicon. PMID- 9978969 TI - Anomalous conductivity and electron-coupling-constant scaling in metallic phosphorous-doped silicon. PMID- 9978970 TI - Theoretical studies of arsine adsorption on Si(100). PMID- 9978971 TI - Phase transition in a many-electron gas in a two-dimensional polar-semiconductor quantum well. PMID- 9978972 TI - Light-emission mechanism of Si-MOS tunnel junctions. PMID- 9978973 TI - X-ray diffraction from laterally structured surfaces: Total external reflection. PMID- 9978974 TI - Plasmon dispersion and electron heating in a drifting two-dimensional electron gas. PMID- 9978976 TI - Interface study of heteroepitaxial diamond films on silicon (001) substrates. PMID- 9978975 TI - Donor 1s-2p+/- transitions in doped GaAs-Ga1-xAlxAs quantum wells: Effects of electric and magnetic fields. PMID- 9978977 TI - Magnetoelectric spectrum and transport properties of a shallow asymmetric quantum channel. PMID- 9978978 TI - Inadequacy of the one-dimensional approximation for resonant-tunneling-diode current-voltage calculations. PMID- 9978979 TI - Conductance-quantization broadening mechanisms in quantum point contacts. PMID- 9978980 TI - Noninteger conductance steps in a gapped double electron waveguide. PMID- 9978981 TI - Resonant electron capture in AlxGa1-xAs/AlAs/GaAs quantum wells. PMID- 9978982 TI - Iron environment in pseudomorphic iron silicides epitaxially grown on Si(111). PMID- 9978983 TI - X-ray diffraction from Si/Ge layers: Diffuse scattering in the region of total external reflection. PMID- 9978984 TI - Laser-induced band-bending variation on room-temperature CdTe(110)1 x 1 surfaces observed in photoemission and through the Franz-Keldish effect in surface differential reflectivity. PMID- 9978985 TI - Band nonparabolicity and central-cell corrections for D- centers in GaAs quantum wells. PMID- 9978986 TI - Geometry and electronic band structure of an ordered monolayer deposition of Bi on III-V(110) semiconductor surfaces. PMID- 9978987 TI - Nuclear-quadrupole-resonance studies of As2Se3 fibers. PMID- 9978988 TI - Cyclotron resonance of two-dimensional interface polarons. PMID- 9978989 TI - Au/n-ZnSe contacts studied with use of ballistic-electron-emission microscopy. PMID- 9978990 TI - Tunneling and quantum noise in one-dimensional Luttinger liquids. PMID- 9978991 TI - Reactive adsorption and diffusion of Ti on Si(001) by scanning tunneling microscopy. PMID- 9978992 TI - Coulomb blockade and current-voltage characteristics of ultrasmall double tunnel junctions with external circuits. PMID- 9978994 TI - Inverse problem for multiple scattering of fast charged particles in a mesoscopic medium. PMID- 9978993 TI - Surface-shift low-energy photoelectron diffraction: Clean and hydrogenated GaAs(110) surface-structure relaxation. PMID- 9978995 TI - Very-low-energy electron-diffraction analysis of oxygen on Cu(001). PMID- 9978997 TI - Ultrathin films of Pt on TiO2(110): Growth and chemisorption-induced surfactant effects. PMID- 9978996 TI - Molecular-quantum-electrodynamics calculation of multipolar optical harmonics generation from isotropic media in the presence of a surface. PMID- 9978998 TI - Order-to-disorder phase-transition study of Pb on Ge(111). PMID- 9979000 TI - Theory of lithium islands and monolayers: Electronic structure and stability. PMID- 9978999 TI - Hexagonal packing of Fe layers in Fe/Ru superlattices. PMID- 9979001 TI - Quantum size effect on optical second-harmonic generation in small metallic particles. PMID- 9979002 TI - Self-annihilation of surface precipitates on compound films by alternate impinging of molecular beams. PMID- 9979003 TI - Inconsistency between height-height correlation and power-spectrum functions of scale-invariant surfaces for roughness exponent alpha ~1. PMID- 9979004 TI - In situ STM studies of Cu underpotential deposition on Au(100) in the presence of sulfate and chloride anions. PMID- 9979006 TI - Time-independent tunneling current of a tip-sample system in scanning tunneling spectroscopy. PMID- 9979005 TI - Coincidence electron spectroscopy of W(100) in the threshold-energy region. PMID- 9979007 TI - Mossbauer investigation of the growth of the Fe multilayer in Fe(100)/Ag(100) structures. PMID- 9979008 TI - Molecular-dynamics study of the dynamical excitations in commensurate monolayer films of nitrogen molecules on graphite: A test of the corrugation in the nitrogen-graphite potential. PMID- 9979010 TI - Growth and structural characterization of Ni/Co superlattices. PMID- 9979009 TI - Electromagnetic surface response for a solid with one-dimensional crystallinity. PMID- 9979011 TI - Hydrodynamic model for second-harmonic generation at conductor surfaces with continuous profiles. PMID- 9979012 TI - Bulk properties of the stabilized uniform interstitial electron gas in metals. PMID- 9979013 TI - Linear-response theory revisited. PMID- 9979014 TI - Theoretical search for ZnSe-based quaternaries. PMID- 9979015 TI - Demonstration of semiconductor characterization by phonon sidebands in photoluminescence. PMID- 9979016 TI - Transport properties of Kondo holes in a Kondo insulator. PMID- 9979018 TI - Hall effect over integral filling factors in GaAs/AlxGa1-xAs quantum wires. PMID- 9979017 TI - Two-parameter scaling of the hopping conductivity of n-type CdSe. PMID- 9979019 TI - Density-functional theory of Wigner crystallization in two dimensions. PMID- 9979020 TI - Binding energy of a hydrogenic donor and of a Wannier exciton in the ||z||2/3 quantum well. PMID- 9979021 TI - Time-resolved spectroscopy of biexciton luminescence in ZnxCd1-xSe-ZnSySe1-y multiple quantum wells. PMID- 9979022 TI - Electric-field and temperature tuning of exciton-photon coupling in quantum microcavity structures. PMID- 9979024 TI - Disorder-induced radiative decay of excitons in type-I indirect-gap quantum wells. PMID- 9979023 TI - Resonance magnetoresistance of coupled quantum wells. PMID- 9979026 TI - Bound on the group velocity of an electron in a one-dimensional periodic potential. PMID- 9979025 TI - Rigorous upper bound for the persistent current in systems with toroidal geometry. PMID- 9979028 TI - Phenomenological equations of the kinetics of heterogeneous adsorption with interaction between adsorbed molecules. PMID- 9979027 TI - Hydrogen-induced reconstruction of W(001): Predictions of the four-position model. PMID- 9979029 TI - Relative stability of hexagonal and planar structures of hypothetical C3N4 solids. PMID- 9979030 TI - Electronic structure of Si46 and Na2Ba6Si46. PMID- 9979031 TI - Two-loop scattering amplitudes for the t-J model: Evidence for a spin-exchange collective mode. PMID- 9979032 TI - Energetics of bond-centered hydrogen in strained Si-Si bonds. PMID- 9979033 TI - Electron states in a quasi-one-dimensional charge channel over liquid helium in the presence of a transverse magnetic field. PMID- 9979034 TI - Weak ferroelectricity in antiferroelectric lead zirconate. PMID- 9979036 TI - Dynamics of order-parameter-conserving Ising models at T>Tc. PMID- 9979035 TI - Temperature dependence of the YAG:Cr3+ fluorescence lifetime over the range 77 to 900 K. PMID- 9979037 TI - Phase-transition mechanism in (NH4)2SO4. PMID- 9979038 TI - Multielectron excitations at the L edges in rare-earth ionic aqueous solutions. PMID- 9979039 TI - Effects of ballistic atom movements on ordering transitions of binary alloys. PMID- 9979040 TI - Frequency dependence of the complex dielectric permittivity of ferroelectric relaxors. PMID- 9979041 TI - Derivation of electron-gas interatomic potentials from quantum-mechanical descriptions of ions in crystals. PMID- 9979042 TI - Computer simulation of vapor-liquid phase separation in two- and three dimensional fluids. II. Domain structure. PMID- 9979043 TI - Path-integral Monte Carlo study of crystalline Lennard-Jones systems. PMID- 9979044 TI - Stacking-fault imaging using transmission ion channeling. PMID- 9979045 TI - Dechanneling of MeV protons by 60 degrees dislocations. PMID- 9979046 TI - Influence of disorder on the field-modulated spectra of polydiacetylene films. PMID- 9979047 TI - Coherent phenomena in inelastic backscattering of electrons from disordered media. PMID- 9979048 TI - Anomalous-diffusion model of ionic transport in oxide glasses. PMID- 9979049 TI - Magnetoconductivity of quasicrystals in the insulating regime. PMID- 9979050 TI - Elastic-wave propagation through disordered and/or absorptive layered systems. PMID- 9979051 TI - Quadrupolar random-field model for orientational glasses. PMID- 9979052 TI - X-ray-diffraction study of structural relaxation in metallic glasses. PMID- 9979054 TI - Ground state of a general electron-phonon Hamiltonian is a spin singlet. PMID- 9979053 TI - Asymmetric exclusion model for mixed ionic conductors. PMID- 9979056 TI - 23Na NMR evidence for a change of diffusion mechanism in NaClO4-poly(propylene oxide). PMID- 9979055 TI - Clump phase in a two-dimensional solitonlike potential. PMID- 9979057 TI - Nonuniversality in random-matrix ensembles with soft level confinement. PMID- 9979058 TI - Nonlinear acoustic response of glasses in the tunneling model. PMID- 9979059 TI - Vibrational study of 13C-enriched C60 crystals. PMID- 9979061 TI - Temperature dependence of phonon lifetimes in dielectric crystals. PMID- 9979060 TI - Specific heat and phase diagrams of H2 adsorbed on D2- or HD-plated graphite. PMID- 9979062 TI - Randomly coupled Ising models. PMID- 9979063 TI - Detailed field- and temperature-dependent ac-susceptibility study of Ru-doped CeFe2. PMID- 9979064 TI - Magnetic phase transitions and crystal-field splitting in K2UX5 (X=Cl,Br,I). PMID- 9979065 TI - Site occupancies of Si atoms and Curie temperatures for Sm2Fe17-xSix. PMID- 9979066 TI - Two-dimensional Heisenberg antiferromagnet with perturbing spin defects. PMID- 9979067 TI - Structure and magnetic properties of RFe11.35Nb0.65 and RFe11.35Nb0.65Ny (R=Y, Sm, Gd, Tb, Dy, Ho, Er, and Lu). PMID- 9979068 TI - Strong anisotropies in MBE-grown Co/Cr(001): Ferromagnetic-resonance and magneto optical Kerr-effect studies. PMID- 9979070 TI - Temperature dependence of magnetic anisotropy and magnetostriction. PMID- 9979069 TI - Ising ferromagnet on a fractal family: Thermodynamical functions and scaling laws. PMID- 9979071 TI - Spin-dependent transmission of polarized electrons through a ferromagnetic iron film. PMID- 9979073 TI - Nonlinear temperature variation of magnetic viscosity in nanoscale FeOOH particles. PMID- 9979072 TI - Green's function study of one-dimensional spin-1/2 Ising-Heisenberg ferromagnets. PMID- 9979074 TI - Thermopower and resistivity behavior in Ce-based Kondo-lattice systems: A phenomenological approach. PMID- 9979076 TI - Two extended versions of the continuous two-dimensional Heisenberg model. PMID- 9979075 TI - Anisotropic two-dimensional Heisenberg model studied by the Schwinger-boson Gutzwiller-projection method. PMID- 9979077 TI - Optical absorption in the phase-modulated antiferromagnetic state of a t-t'-J model. PMID- 9979078 TI - Thermodynamic analysis of Fe72Pt28 Invar. PMID- 9979079 TI - Electronic structures of CeNiSn, CePdSn, and CePtSn. PMID- 9979080 TI - Magnetic phase diagram of the UFe1-xNixAl system. PMID- 9979081 TI - Chemical bonding in the UFe1-xNixAl alloys. PMID- 9979082 TI - Raman study of one-dimensional spin fluctuations in the spin-1 Heisenberg-chain compound Y2BaNiO5: Contrast with simple expectations. PMID- 9979083 TI - Spiral spin states in a generalized Kondo lattice model with classical localized spins. PMID- 9979084 TI - Metal-semimetal transitions in the extended Hubbard model on the fcc lattice: Implications for superconducting fullerides. PMID- 9979085 TI - Locations of Rb ions in A2RbC60 (A=Na,K) superconductors. PMID- 9979086 TI - Phase coherence in two-dimensional type-II superconductors. PMID- 9979088 TI - Electromagnetic waves in a Josephson junction in a thin film. PMID- 9979087 TI - One-dimensional bosons, the Luther-Emery condition, and phase transitions in low dimensional systems. PMID- 9979090 TI - Frustrated XY models with accidental degeneracy of the ground state. PMID- 9979089 TI - Atomic- and electron-beam spectroscopy of rarefied semiquantum media. PMID- 9979091 TI - Experimental and numerical study of dynamic regimes in a discrete sine-Gordon lattice. PMID- 9979092 TI - Onset of vortices in thin superconducting strips and wires. PMID- 9979093 TI - Growth-kinetics-induced structural disorder in Bi2(Sr1-xCax)3Cu2Oy thin films studied by x-ray diffraction. PMID- 9979094 TI - Thermoelectric power in single-layer copper oxides. PMID- 9979095 TI - Thermopower of an untwinned YBa2Cu3O7- delta crystal. PMID- 9979097 TI - Structural modifications in bismuth cuprates: Effects on the electronic structure and Fermi surface. PMID- 9979096 TI - Crossover from two-dimensional to three-dimensional magnetic structure in Pr1.5Ce0.5Sr2GaCu2O9. PMID- 9979098 TI - Normal-state reentrant behavior in superconducting Bi2Sr2CaCu2O8/Bi2Sr2Ca2Cu3O10 intergrowth single crystals. PMID- 9979099 TI - Softening of a reststrahlen band in CuO near the Neel transition. PMID- 9979100 TI - Elastic broadening of quasiparticle energy levels in vortex cores of high-Tc superconductors. PMID- 9979101 TI - Loop-expansion study of the single-hole spectral function in the t-J model. PMID- 9979102 TI - 63,65Cu and 17O spin-echo decay and the static susceptibility chi '(q) in La1.85Sr0.15CuO4. PMID- 9979103 TI - Neutron-diffraction studies on the time dependence of the oxygen ordering in La2NiO4.105. PMID- 9979105 TI - Density of states in layered superconductor-insulator structures. PMID- 9979104 TI - Emergence of two superconducting phases (33 K and 40 K) and their relation to structural phase transitions in crystalline La2CuO4.011. PMID- 9979107 TI - Crystal and electronic structures of the two-dimensional transition-metal-complex molecule alpha - PMID- 9979106 TI - Pressure-induced metallization of ZnSe. PMID- 9979108 TI - 2p-3d resonant Auger scattering by K+ ions of KMnF3 without the influence of the crystal-field splitting. PMID- 9979109 TI - Optical and ESR study of Er3+ in LiNbO3. PMID- 9979111 TI - Perturbed phonons in pyrolytic graphite studied by neutron-scattering techniques. PMID- 9979110 TI - Infrared and Raman evidence for dimers and polymers in RbC60. PMID- 9979112 TI - Asymmetric impurity modes in nonlinear lattices. PMID- 9979113 TI - Spin-density distribution in ferromagnetic alpha "-Fe16N2. PMID- 9979114 TI - Prediction and measurement of perpendicular giant magnetoresistances of Co/Cu/Ni84Fe16/Cu multilayers. PMID- 9979115 TI - Induced spin polarization and interlayer exchange coupling of the systems Rh/Co(0001) and Ru/Co(0001). PMID- 9979116 TI - Absence of the anomalous second length scale in the bulk of a terbium single crystal. PMID- 9979117 TI - Effects of an electrostatic field on the normal and superconducting states of a Mo-C film. PMID- 9979118 TI - Pair excitations in the ground state of a two-dimensional attractive Fermi gas. PMID- 9979119 TI - Anharmonic electron and phonon effects in the c-axis infrared conductivity of high-Tc oxides. PMID- 9979120 TI - Chain contribution to the Seebeck coefficient in YBa2Cu3O7- delta. PMID- 9979121 TI - Landau theory of phase separation in cuprates. PMID- 9979122 TI - Mechanism of the electric-field effect in the high-Tc cuprates. PMID- 9979123 TI - Thermodynamic parameters of HgBa2Ca2Cu3O8-x from high-field magnetization. PMID- 9979125 TI - Dependence of the Josephson coupling of unconventional superconductors on the properties of the tunneling barrier. PMID- 9979124 TI - c-axis charge dynamics in the bilayer t-J model: A numerical study. PMID- 9979126 TI - Comment on "Localization in a one-dimensional Thue-Morse chain" PMID- 9979127 TI - Reply to "Comment on 'Localization in a one-dimensional Thue-Morse chain' " PMID- 9979128 TI - Evidence for possible 4f bands at T >> TK in the heavy-fermion single crystal CePt2+x. PMID- 9979129 TI - Iron exchange-field penetration into the amorphous interphase of nanocrystalline materials. PMID- 9979130 TI - Metal-phase stability of (TMTSF)2ClO4 in high magnetic fields, where TMTSF is tetramethyltetraselenafulvalene. PMID- 9979131 TI - Spin correlations at finite temperature in an S=1 one-dimensional antiferromagnet. PMID- 9979132 TI - X-ray magnetic-circular-dichroism study of Fe/V multilayers. PMID- 9979133 TI - Magnetic and electronic properties in hole-doped manganese oxides with layered structures: La1-xSr1+xMnO4. PMID- 9979134 TI - Anomalous vortex dynamics in kappa - PMID- 9979135 TI - Nonergodic dynamics of the two-dimensional random-phase sine-Gordon model: Applications to vortex-glass arrays and disordered-substrate surfaces. PMID- 9979136 TI - Metallic ground state of CuO chains in high-temperature superconductors. PMID- 9979137 TI - ab-plane optical properties of Tl2Ba2CuO6+ delta. PMID- 9979139 TI - Erratum: Dielectric relaxation and piezoelectric coupling in the mixed proton glass crystal K0.61(NH4)0.39H2PO4 PMID- 9979138 TI - Anisotropic surface impedance of YBa2Cu3O7- delta single crystals. PMID- 9979141 TI - Quenching of the total luminescence of Ho3+ in HoLiF4 crystals. PMID- 9979140 TI - Time-resolved differential fragmentation cross sections of C60++C60 collisions. PMID- 9979142 TI - Elastic softening in the rotator phase of the perfluoroalkane C24F50. PMID- 9979143 TI - Elastic scattering of polarized light in multiply domained KH2PO4. PMID- 9979145 TI - Modified-hypernetted-chain determination of the phase diagram of rigid C60 molecules. PMID- 9979144 TI - Symmetry breaking and structural changes at the neutral-to-ionic transition in tetrathiafulvalene-p-chloranil. PMID- 9979146 TI - Ab initio study of the structural properties of LiF, NaF, KF, LiCl, NaCl, and KCl. PMID- 9979147 TI - Theory of electron backscattering from crystals. PMID- 9979148 TI - Augmented-space recursive technique for the analysis of alloy phase stability in random binary alloys. PMID- 9979149 TI - Crystal growth in undercooled melts of the intermetallic compounds FeSi and CoSi. PMID- 9979150 TI - Reciprocal-space analysis of short-range-order intensities by the cluster variation method. PMID- 9979151 TI - Inhomogeneous broadening of electron-paramagnetic-resonance and optical spectra of V4+ in CaYAlO4. PMID- 9979152 TI - Valence electronic structure of polycrystalline SiC as observed by (e,2e) spectroscopy. PMID- 9979153 TI - Three-body effect on the lattice dynamics of Pd-10% Fe alloys. PMID- 9979154 TI - Quantum tunneling in solid D2 and solid H2. PMID- 9979156 TI - Breakdown of two-phase random resistor networks. PMID- 9979155 TI - Energy and charge trapping by localized vibrations: Electron-vibrational coupling in anharmonic lattices. PMID- 9979158 TI - Jahn-Teller effect and on-site interaction for C60n- PMID- 9979157 TI - Violent fluctuations of the fracton density of states on the percolation cluster and its backbone. PMID- 9979159 TI - Resonances in driven dynamical lattices. PMID- 9979161 TI - Adiabatic theory for the bipolaron. PMID- 9979160 TI - Normal and anomalous nuclear spin-lattice relaxation at high temperatures in Sc H(D), Y-H, and Lu-H solid solutions. PMID- 9979163 TI - Thermoelastic properties of perfect crystals with nonprimitive lattices. II. Application to KCl and NaCl. PMID- 9979162 TI - Thermoelastic properties of perfect crystals with nonprimitive lattices. I. General theory. PMID- 9979164 TI - Strain-induced perpendicular magnetic anisotropy of <100>-oriented Ni-Cu superlattices. PMID- 9979165 TI - Kondo scattering from atomic two-level tunneling systems in metals: Enhanced conductance, critical-bias transitions, and the non-Fermi-liquid electronic state. PMID- 9979166 TI - Magnetic properties of NdNi1-xCoxO3 samples: Evidence of spin-glass behavior. PMID- 9979167 TI - Effect of fractons on the exciton dynamics in dilute magnets. PMID- 9979168 TI - Analysis of the dependence of spin-spin correlations on the thermal treatment of nanocrystalline materials. PMID- 9979169 TI - Effect of a magnetic field on Ni-Pt alloys. PMID- 9979171 TI - Phase transitions in Ising ferromagnets with biquadratic exchange interactions. PMID- 9979170 TI - Microscopic magnetization reversal processes and magnetic domain structure in epitaxial Fe/GaAs(001) films. PMID- 9979172 TI - Ground-state properties of a spin-1 Heisenberg ferromagnet with an arbitrary crystal-field potential. PMID- 9979174 TI - Search for the nondimerized quantum nematic phase in the spin-1 chain. PMID- 9979173 TI - Random frustration in a two-dimensional spin-1/2 Heisenberg antiferromagnet. PMID- 9979175 TI - Neel orders, Haldane gap, and Kondo singlet phase in the anisotropic Kondo chain. PMID- 9979176 TI - Extraordinary Hall effect in magnetic multilayers. PMID- 9979178 TI - Interlayer-coupling energy of magnetic trilayers in a one-band tight-binding model. PMID- 9979177 TI - Mean-field renormalization-group approaches to the surface on a semi-infinite Ising model with a random surface field. PMID- 9979179 TI - Magnetization of S=1 antiferromagnetic Heisenberg chains. PMID- 9979181 TI - Nonequilibrium in normal-conductor/superconductor microconstrictions. PMID- 9979180 TI - Temperature dependence of the normal and inverse magnetoresistance in magnetic multilayers. PMID- 9979183 TI - Optical study of electronic structures and phonons in alkali-metal-doped C60. PMID- 9979182 TI - Comparison of strontium-induced and oxygen-induced holes in La2CuO4. PMID- 9979184 TI - Magnetic self-field entry into a current-carrying type-II superconductor. II. Helical vortices in a longitudinal magnetic field. PMID- 9979185 TI - Motion of a Josephson vortex under a temperature gradient. PMID- 9979186 TI - Neutron-powder-diffraction study of the nuclear and magnetic structures of the antiferromagnetic superconductor HoNi2B2C. PMID- 9979187 TI - Space-time tunneling bosonization: An application to the N-coupled Luttinger chains. PMID- 9979189 TI - 2D-3D vortex-line transition in two-layer Josephson arrays. PMID- 9979188 TI - Phase diagram of multiply connected superconductors: A thin-wire loop and a thin film with a circular hole. PMID- 9979191 TI - Self-consistent theory of superconducting mesoscopic weak links. PMID- 9979190 TI - Enhanced electron pairing in a lattice of Berry-phase molecules. PMID- 9979192 TI - Superconducting current in a ballistic double superconducting-normal-metal superconducting structure. PMID- 9979193 TI - Off-diagonal long-range order: Meissner effect and flux quantization. PMID- 9979194 TI - Vortex-chain state in Bi2Sr2CaCu2O8+ delta : Experimental evidence for coexistence of two vortex orientations. PMID- 9979195 TI - Infrared and microwave spectra of an energy gap in high-temperature superconductors. PMID- 9979196 TI - Field- and temperature-dependent surface resistance of superconducting polycrystalline multiple-phase Hg-Ba-Ca-Cu-O: Evidence for dirty-limit behavior. PMID- 9979197 TI - Cu 2p core-level XPS of Nd1.85Ce0.15CuOy: An analysis from bond valence sums and Madelung potentials. PMID- 9979198 TI - Nesting mechanism for d-symmetry superconductors. PMID- 9979199 TI - Fluctuation of vortices and the fluxon transition in Bi2Sr2CaCu2O8+y single crystals. PMID- 9979201 TI - Quantum interference and critical currents in polycrystalline high-Tc samples. PMID- 9979200 TI - Tunneling, alpha 2F( omega ), and transport in superconductors: Nb, V, VN, Ba1 xKxBiO3, and Nd1.85Ce0.15CuO4. PMID- 9979202 TI - Structure and relaxation of the trapped magnetic flux in Y-Ba-Cu-O superconductors in magnetic fields below the first critical field Hc1. PMID- 9979204 TI - Electron-phonon coupling and d-wave superconductivity in the cuprates. PMID- 9979203 TI - Observation of a van Hove singularity in Bi2Sr2CaCu2O8+x with angle-resolved photoemission. PMID- 9979205 TI - Correlation-enhanced electron-phonon interaction in a strongly correlated electron system. PMID- 9979206 TI - Gauge symmetry breaking, collective modes, and boson superconductivity in the t-J model. PMID- 9979207 TI - Gauge invariance and transport properties in superconductors above Tc. PMID- 9979208 TI - Ab initio pseudopotential plane-wave calculations of the electronic structure of YBa2Cu3O7. PMID- 9979209 TI - Superconducting and magnetic properties of TlSr2Ca1-xRxCu2O7 PMID- 9979210 TI - Shear relaxation of (NaCN)1-x(KCN)x quadrupolar glasses. PMID- 9979211 TI - High-pressure transitions to a postcotunnite phase in ionic AX2 compounds. PMID- 9979212 TI - Differences in elastic behavior between pentagonal and decagonal quasicrystals. PMID- 9979213 TI - Hierarchical mobility edges in a class of one-dimensional generalized Fibonacci quasilattices. PMID- 9979215 TI - Linear approximation in the kinetic Ising model on fractals. PMID- 9979214 TI - Structural study of silica particle dispersions by ultra-small-angle x-ray scattering. PMID- 9979216 TI - Large-cell renormalization group and order parameter for site percolation problems. PMID- 9979217 TI - Giant magnetoimpedance in the ferromagnetic alloy Co75-xFexSi15B10. PMID- 9979218 TI - Magnon-excitation contribution to the interface magnetization in Co/Cu superlattices. PMID- 9979220 TI - Magnetic properties of layered antiferromagnets. PMID- 9979219 TI - Dipolar effects in a Heisenberg ferromagnetic bilayer. PMID- 9979221 TI - Superconducting critical temperature for realistic couplings. PMID- 9979222 TI - Anisotropy of the electronic structure and superconducting gap in Bi2Sr2CaCu2O8. PMID- 9979223 TI - Effect of strong correlation on the in-plane electronic properties of the high-Tc superconductors. PMID- 9979224 TI - Bose-glass behavior of the vortex system in epitaxial Bi2Sr2CaCu2O8+ delta films with columnar defects. PMID- 9979225 TI - Experimental evidence for Bose-glass behavior in Bi2Sr2CaCu2O8 crystals with columnar defects. PMID- 9979226 TI - Momentum dependence of the linewidth of Raman-active phonons in the normal state of YBa2Cu3O7. PMID- 9979227 TI - Comment on "Quadrupolar glass freezing in solid hydrogen: Distribution functions for the orientational order parameters" PMID- 9979228 TI - Phase transitions in KC60: Dimer formation via rapid quenching. PMID- 9979229 TI - Effect of finite concentration in Kondo alloys: Approach to the heavy-fermion problem. PMID- 9979231 TI - Electronic localization in Rb4C60 from bulk magnetic measurements. PMID- 9979230 TI - Equilibrium dynamics of a paramagnetic cluster. PMID- 9979232 TI - Hall-effect studies of the mixed state of Y1-xPrxBa2Cu3O7- delta (0 <= x <= 0.42) and YBa2Cu3Oy (6.65 <= y <= 6.84) single crystals. PMID- 9979233 TI - Superconducting energy gap and antiferromagnetic spin fluctuations in the superconductor YNi2B2C: An NMR study. PMID- 9979234 TI - Quantum Hall effect in a vortex liquid. PMID- 9979235 TI - Bi3.9Sr3.3Ca1.3(Cu0.961Fe0.039)3Ox: A high-Tc structure close to the two dimensional limit. PMID- 9979236 TI - Electronic structures of gallium and indium across the solid-liquid transition. PMID- 9979237 TI - Periodic boundary conditions in ab initio calculations. PMID- 9979238 TI - Electronic structure of icosahedral Al65Cu20Ru15 studied by photoemission spectroscopy. PMID- 9979239 TI - Incommensurate ground states in a one-dimensional model for electron-libron coupling in polyaniline. PMID- 9979240 TI - Electronic states and transport in quasicrystals investigated by perturbation theory. PMID- 9979241 TI - Site preference of ternary additions in Ni3Al. PMID- 9979242 TI - Optimized l-convergency in the solution of Poisson's equation with space-filling cells. PMID- 9979243 TI - Universal statistics of transport in disordered conductors. PMID- 9979244 TI - Exact solution of the Landau fixed point via bosonization. PMID- 9979245 TI - All-electron study of gradient corrections to the local-density functional in metallic systems. PMID- 9979246 TI - Kondo-lattice model in infinite dimensions. PMID- 9979247 TI - Theoretical investigation of the pressure-induced metallization and the collapse of the antiferromagnetic state of NiI2. PMID- 9979248 TI - Application of the coupled-cluster method to the periodic Anderson model. PMID- 9979249 TI - Metal-insulator transition in semiconductor alloys probed by persistent photoconductivity. PMID- 9979250 TI - Conductance and localization in a system of coupled conjugated polymer chains. PMID- 9979251 TI - Semiclassical density-of-states and optical-absorption analysis of amorphous semiconductors. PMID- 9979253 TI - Many-body theory of room-temperature optical nonlinearities in bulk semiconductors. PMID- 9979252 TI - Dynamics of the H-CAs complex in GaAs determined from Raman measurements. PMID- 9979254 TI - Theoretical study of H-P and H-B complexes in silicon. PMID- 9979256 TI - Identification of vacancy defects in compound semiconductors by core-electron annihilation: Application to InP. PMID- 9979255 TI - Hydrogen passivation of EL2 defects and H2*-like complex formation in gallium arsenide. PMID- 9979257 TI - Observation of quasidirect transitions in In1-xGaxP/graded GaP (0.58 <= x <= 0.75) alloys near the Gamma -X1 crossover. PMID- 9979258 TI - Absolute negative resistance in double-barrier heterostructures in a strong laser field. PMID- 9979259 TI - Determination of the surface structures of the GaAs(001)-(2 x 4) As-rich phase. PMID- 9979260 TI - Quantum confinement of holes in Si1-xGex/Si quantum wells studied by admittance spectroscopy. PMID- 9979261 TI - Generalized diffusion-reaction model for the low-field charge-buildup instability at the Si-SiO2 interface. PMID- 9979262 TI - Atomic bond configuration of Ge(111)-( sqrt 3 x sqrt 3 )R30 degrees-Au: A low energy electron-diffraction study. PMID- 9979263 TI - Electric-field effects on above-barrier states in a GaAs/AlxGa1-xAs superlattice. PMID- 9979264 TI - Excitation-induced phase shifts of heavy- and light-hole quantum beats in GaAs/AlxGa1-xAs multiple quantum wells. PMID- 9979266 TI - Surface band structure of Si(111)2 x 1. PMID- 9979265 TI - Spin relaxation in intrinsic GaAs quantum wells: Influence of excitonic localization. PMID- 9979268 TI - Linear polarization of photoluminescence emission and absorption in quantum-well wire structures: Experiment and theory. PMID- 9979267 TI - AlxGa1-xAs intervalley scattering rates from field-assisted photoemission spectroscopy. PMID- 9979269 TI - Effect of a magnetic field on the excitonic luminescence line shape in a quantum well. PMID- 9979270 TI - Optical Fermi-edge singularities in a one-dimensional electron system with tunable effective mass. PMID- 9979271 TI - Current-voltage calculations for InAs/AlSb resonant-tunneling diodes. PMID- 9979272 TI - Energy gaps in strained In1-xGaxAs/In1-yGayAszP1-z quantum wells grown on (001) InP. PMID- 9979274 TI - Longitudinal magnetoresistance in semiconductor superlattices. PMID- 9979273 TI - Quantum Hall effect in three-dimensional field-induced spin-density-wave phases with a tilted magnetic field. PMID- 9979275 TI - Temperature dependence of the intersubband transitions of doped quantum wells. PMID- 9979276 TI - Atomic structure of Na-adsorbed Si(100) surfaces. PMID- 9979277 TI - Aharonov-Bohm effect in quasi-one-dimensional In0.77Ga0.23As/InP rings. PMID- 9979278 TI - Quasiparticle excitations in GaAs1-xNx and AlAs1-xNx ordered alloys. PMID- 9979279 TI - Fermionic Chern-Simons theory for the fractional quantum Hall effect in bilayers. PMID- 9979280 TI - Influence of the form of disorder on the persistent current of an interacting system. PMID- 9979281 TI - Strain and piezoelectric fields in arbitrarily oriented semiconductor heterostructures. I. Multiple quantum wells. PMID- 9979282 TI - Strain and piezoelectric fields in arbitrarily oriented semiconductor heterostructures. II. Quantum wires. PMID- 9979283 TI - Interfacial strain-enhanced reconstruction of Au multilayer films on Rh(100). PMID- 9979284 TI - Scanning-tunneling-microscopy observation of K-induced reconstructions on Au(110). PMID- 9979285 TI - Onset of fast step-velocity oscillations during growth by molecular-beam epitaxy. PMID- 9979286 TI - Coverage dependence of quantum tunneling diffusion of hydrogen and deuterium on Ni(111). PMID- 9979287 TI - Molecular-dynamics description of early film deposition of Au on Ag(110). PMID- 9979288 TI - Vapor-pressure-isotherm study of monolayer CO films adsorbed on BN. PMID- 9979289 TI - X-ray-scattering studies of the interfacial structure of Au/GaAs. PMID- 9979290 TI - Excitons and exciton confinement in crystalline organic thin films grown by organic molecular-beam deposition. PMID- 9979292 TI - Interaction of H2 and He with metal atoms, clusters, and ions. PMID- 9979291 TI - Low-energy H+, He+, N+, O+, and Ne+ scattering from metal and ionic-compound surfaces: Neutralization and electronic excitation. PMID- 9979293 TI - Au overlayer structures on a Ni(110) surface. PMID- 9979294 TI - Electronic structure and elastic properties of Au/Cr(001) superlattices. PMID- 9979295 TI - Effect of silver-nanoparticle aggregation on surface-enhanced Raman scattering from benzoic acid. PMID- 9979296 TI - Interaction of hydrogen with TaC(111) and NbC(111) surfaces: Angle-resolved photoemission study. PMID- 9979297 TI - Molecular-statics and molecular-dynamics study of diffusion along PMID- 9979298 TI - Elucidation of hydrogen-induced (1 x 2) reconstructed structures on Pd(110) from 100 to 300 K by scanning tunneling microscopy. PMID- 9979299 TI - Force-constant model of a fullerene based on a first-principles method and bond population analysis: Applications to C60 and C70. PMID- 9979300 TI - Molecular-dynamics subplantation studies of carbon beneath the diamond (111) surface. PMID- 9979302 TI - Inelastic electron scattering and magnetic collective response of mesoscopic carbon structures. PMID- 9979301 TI - Optical absorption and photoluminescence in pristine and photopolymerized C60 solid films. PMID- 9979303 TI - Ground-state correlations and linear response of metal clusters. PMID- 9979305 TI - Transmission of low-energy O+ ions through ultrathin films of Ar, Kr, and Xe. PMID- 9979304 TI - Dynamics of step roughening on vicinal surfaces. PMID- 9979306 TI - Transmission of low-energy oxygen ions through ultrathin rare-gas films: Molecular-dynamics simulation. PMID- 9979307 TI - Electronic dispersion relations of monolayer hexagonal boron nitride formed on the Ni(111) surface. PMID- 9979308 TI - Time-resolved optical Kerr response of C84 in CS2. PMID- 9979310 TI - Monte Carlo simulation of high-field hopping on a bond-disordered lattice. PMID- 9979309 TI - Density-functional calculations for cerium metal. PMID- 9979311 TI - Tilted magnetic field effect on a double-layer quantum Hall system. PMID- 9979312 TI - Hydrogen-induced breakdown of low-temperature molecular-beam epitaxy of Si. PMID- 9979313 TI - Excitonic nonlinear optical processes in GaAs quantum-well wires. PMID- 9979314 TI - Magneto-optical absorption spectrum of a D- ion in a GaAs-Ga0.75Al0.25As quantum well. PMID- 9979315 TI - Electric-field-induced changes in the transmission spectrum of a superlattice. PMID- 9979316 TI - Finite-temperature fractional quantum Hall effect. PMID- 9979318 TI - Broadening of quantum-dot energy levels due to short-range elastic scatterers. PMID- 9979317 TI - Observation of large h/2e oscillations in semiconductor antidot lattices. PMID- 9979319 TI - Dynamics of carrier-capture processes in GaxIn1-xAs/GaAs near-surface quantum wells. PMID- 9979320 TI - Structural analyses of Cs+CO coadsorbed on Ru(0001). PMID- 9979321 TI - Matrix effects of secondary neutrals: Laser postionization investigations of particles sputtered from clean and oxidized metals. PMID- 9979322 TI - Photoelectron spectroscopy of transition-metal clusters: Correlation of valence electronic structure to reactivity. PMID- 9979323 TI - Optical transmittance of a two-dimensional triangular photonic lattice. PMID- 9979324 TI - Exact results for the Kondo effect in a Luttinger liquid. PMID- 9979326 TI - Photoinduced Hall-current measurements in photorefractive sillenites. PMID- 9979325 TI - Influence of the carrier distribution on carrier-carrier scattering in GaAs. PMID- 9979327 TI - Nature of anticrossing between donor energy levels in GaAs. PMID- 9979329 TI - Electron-acoustic-phonon scattering rates in cylindrical quantum wires. PMID- 9979328 TI - Reflectance anisotropy spectroscopy and reflection high-energy electron diffraction of submonolayer coverages of Si grown on GaAs(001) by molecular-beam epitaxy. PMID- 9979330 TI - Band offsets and exciton binding energies in Zn1-xCdxSe-ZnSe quantum wells grown by metal-organic vapor-phase epitaxy. PMID- 9979332 TI - Spin orientation at semiconductor heterointerfaces. PMID- 9979331 TI - Effect of phase breaking on quantum transport through chaotic cavities. PMID- 9979333 TI - Direct evidence of tunneling between edge states across a gate-induced potential barrier. PMID- 9979335 TI - Femtosecond dephasing in CdS quantum dots determined by nondegenerate four-wave mixing. PMID- 9979334 TI - Kondo resonance in tunneling phenomena through a single quantum level. PMID- 9979336 TI - Interface intermixing influence on the electronic and optical properties of Si/Ge strained-layer superlattices. PMID- 9979337 TI - General relation between density of states and dwell times in mesoscopic systems. PMID- 9979338 TI - Dislocations and the reconstruction of (111) fcc metal surfaces. PMID- 9979339 TI - Absolute appearance energy of Li+ ions field-desorbed from W(111). PMID- 9979341 TI - Electron-electron correlations in diamond: An x-ray-scattering experiment. PMID- 9979340 TI - Effects of Ce-Lu substitution on the d valence states of Laves phases. PMID- 9979342 TI - Thermodynamics of FeSi. PMID- 9979343 TI - Electronic structure of point defects in rutile TiO2. PMID- 9979344 TI - Stability of the Peierls instability for ring-shaped molecules. PMID- 9979345 TI - Dielectric relaxation in a Rb0.30MoO3 crystal. PMID- 9979346 TI - Magnetoconductance of quasicrystals and their approximants: A study of quantum interference effects. PMID- 9979347 TI - Bosonization on a lattice: The emergence of the higher harmonics. PMID- 9979348 TI - Electronic structure of graphite: Effect of hydrostatic pressure. PMID- 9979349 TI - Impurity spin coupled to a strongly correlated electron system: Ground-state properties. PMID- 9979350 TI - Electronic structure and optical response of L-CePd5. PMID- 9979351 TI - Optical spectroscopy of the metal-insulator transition in NdNiO3. PMID- 9979352 TI - Relaxation of a hot-electron-two-mode-phonon system in highly excited CdS1-xSex crystals. PMID- 9979353 TI - Photoacoustic spectroscopic study of energy gap, optical absorption, and thermal diffusivity of polycrystalline ZnSexTe1-x (0 <= x <= 1) alloys. PMID- 9979354 TI - Excitation spectrum of Fe2+ in a tetrahedral potential: Dynamic Jahn-Teller effect. PMID- 9979355 TI - Exciton localization by magnetic polarons and alloy fluctuations in the diluted magnetic semiconductor Cd1-xMnxTe. PMID- 9979356 TI - NMR study of the electronic properties and crystal structure of the semiconducting compound Al2Ru. PMID- 9979357 TI - Hydrogen-mediated creation and annihilation of strain in amorphous silicon. PMID- 9979359 TI - Empirical interatomic potential for Si-H interactions. PMID- 9979358 TI - Photoluminescence of excitons bound to the isoelectronic hydrogen-related defects B80(1.1470 eV) and B191(1.1431 eV) in silicon. PMID- 9979360 TI - Structural properties of Si1-xGex alloys: A Monte Carlo simulation with the Stillinger-Weber potential. PMID- 9979362 TI - Optical properties of HgSe. PMID- 9979361 TI - Composition and thermal-annealing-induced short-range ordering changes in amorphous hydrogenated silicon carbide films as investigated by extended x-ray absorption fine structure and infrared absorption. PMID- 9979363 TI - Calculated structural and electronic properties of CdSe under pressure. PMID- 9979364 TI - Full-zone hole dispersion relations in Si using Schur-complement decomposition. PMID- 9979365 TI - Electromagnetic fields and dielectric response in empirical tight-binding theory. PMID- 9979366 TI - Plasmon and quasiparticle band structures in beta -SiC. PMID- 9979367 TI - Quantum interference in the system of Lorentzian and Fano magnetoexciton resonances in GaAs. PMID- 9979368 TI - Effects of site correlations on the local structure of strain-relaxed semiconductor alloys. PMID- 9979369 TI - Simple trial function for shallow donor D0 states in GaAs-Ga1-xAlxAs quantum-well structures. PMID- 9979370 TI - Electron-spin-resonance analysis of the natural intrinsic EX center in thermal SiO2 on Si. PMID- 9979371 TI - Location of deuterium on the silicon (100) monohydride surface determined by transmission-ion channeling. PMID- 9979372 TI - Center-of-mass quantization of excitons in CdTe/Cd1-xZnxTe quantum wells. PMID- 9979373 TI - Plasmons in lateral-surface superlattices with periodically structured interfaces under normally applied electric fields. PMID- 9979374 TI - Microscopic-scale lateral inhomogeneities of the GaSe-Ge heterojunction energy lineup. PMID- 9979375 TI - Lateral n-i-p-i superlattices in Si metal-oxide-semiconductor structures. PMID- 9979376 TI - Relaxation-induced polarized luminescence from InxGa1-xAs films grown on GaAs(001). PMID- 9979377 TI - Theoretical and experimental investigations of the electronic structure for selectively delta -doped strained InxGa1-xAs/GaAs quantum wells. PMID- 9979378 TI - Rb adsorption on the Si(001)2 x 1 surface: An x-ray-standing-waves study. PMID- 9979379 TI - Magnetic von Neumann lattice for two-dimensional electrons in a magnetic field. PMID- 9979381 TI - Low-temperature growth and ion-assisted deposition. PMID- 9979380 TI - Atomic structure of the Sb/Si(100)-(2 x 1) surface. PMID- 9979382 TI - Magnetoresistance of a two-dimensional electron gas in a square superlattice. PMID- 9979383 TI - Phase considerations in the Thomas-WKB theory: Film structures, quantum wells, and quantum wires. PMID- 9979384 TI - Electric-field dependence of low-temperature recombination in a-Si:H. PMID- 9979385 TI - Monte Carlo simulations for metastable impurity states in delta -doping superlattices. PMID- 9979386 TI - Electron-electron interaction in ballistic electron beams. PMID- 9979387 TI - Disorder effects on luminescence in delta -doped n-i-p-i superlattices. PMID- 9979388 TI - Shot-noise suppression in resonant tunneling. PMID- 9979389 TI - Tight-binding calculation of spin splittings in semiconductor superlattices. PMID- 9979390 TI - Coherent transport through a coupled-quantum-dot system with strong intradot interaction. PMID- 9979392 TI - Excitonic properties of Zn1-xCdxSe/ZnSe strained quantum wells. PMID- 9979391 TI - Spontaneous interlayer coherence in double-layer quantum Hall systems: Charged vortices and Kosterlitz-Thouless phase transitions. PMID- 9979393 TI - Exciton spectroscopy in Zn1-xCdxSe/ZnSe quantum wells. PMID- 9979394 TI - Balance equations for hot-electron transport in a general energy band in crossed magnetic and electric fields. PMID- 9979395 TI - Optical properties of the Pb2+-based aggregated phase in a CsCl host crystal: Quantum-confinement effects. PMID- 9979396 TI - Energetics of vicinal Si(111) steps using empirical potentials. PMID- 9979397 TI - Influence of electromagnetic environmental fluctuations on resonant tunneling through double-barrier systems. PMID- 9979398 TI - Phonon-assisted ballistic resistance. PMID- 9979399 TI - Conductance fluctuations due to a bistable scatterer in a weakly connected conductor. PMID- 9979400 TI - Vibrational properties of the Si(111)Ga( sqrt 3 x sqrt 3 ) surface. PMID- 9979401 TI - Haldane's fractional exclusion statistics for multicomponent systems. PMID- 9979402 TI - Light-assisted magnetotunneling through a semiconductor double-barrier structure. PMID- 9979404 TI - Strains in epitaxial films: The general case. PMID- 9979403 TI - Quenching of excitonic quantum-well photoluminescence by intense far-infrared radiation: Free-carrier heating. PMID- 9979405 TI - Interaction of ytterbium with solid ammonia and xenon studied using photoelectron spectroscopy. PMID- 9979406 TI - Carbon nitride films synthesized by combined ion-beam and laser-ablation processing. PMID- 9979407 TI - First-principles calculation of the electronic structure for a bielectrode junction system under strong field and current. PMID- 9979408 TI - Surface structures and electron affinities of bare and hydrogenated diamond C(100) surfaces. PMID- 9979409 TI - X-ray reflection and transmission by rough surfaces. PMID- 9979410 TI - Adsorbate structure in the H-induced p4g reconstruction of the Cu(001) surface. PMID- 9979411 TI - Surface and size effects on ferroelectric films with domain structures. PMID- 9979412 TI - Evidence for truncated octahedral structures in supported gold clusters. PMID- 9979413 TI - Elastic properties of individual nanometer-size supported gold clusters. PMID- 9979414 TI - Theory of surface polaritons in polycrystals. PMID- 9979415 TI - Diffuse-x-ray-scattering measurements of roughness on ion-etched multilayer interfaces. PMID- 9979417 TI - Theory of the optical and microwave properties of metal-dielectric films. PMID- 9979416 TI - Growth kinetics of CaF2/Si(111) heteroepitaxy: An x-ray photoelectron diffraction study. PMID- 9979418 TI - Surface shift of the occupied and unoccupied 4f levels of the rare-earth metals. PMID- 9979419 TI - High stability of two-dimensional islands during surfactant-mediated epitaxial growth. PMID- 9979420 TI - Unified treatment of temperature, concentration, and electric-field dependences of variable-range-hopping conductivity. PMID- 9979422 TI - Ultrathin films of body-centered-cubic Co on TiAl(010). PMID- 9979421 TI - Metal-ceramic interfaces: Overlayer-induced reconstruction and magnetism of 4d transition-metal monolayers. PMID- 9979423 TI - Low-energy electron scattering by N2 molecules physisorbed on Ag: Study of the resonant vibrational excitation process. PMID- 9979424 TI - Electronic structure of vacancies in amorphous silicon. PMID- 9979425 TI - Inhomogeneous charge transfer in an incommensurate system. PMID- 9979426 TI - Hydrogenation of Si(113) surfaces by photoelectrochemical treatment. PMID- 9979427 TI - Persistent currents without parity effect. PMID- 9979428 TI - Two-dimensional electron-lattice scattering at low temperature. PMID- 9979429 TI - Hot-phonon generation in GaAs/AlxGa1-xAs superlattices: Observations and implications on the coherence length of LO phonons. PMID- 9979430 TI - Resonant tunneling of a Wannier exciton through a single-barrier heterostructure. PMID- 9979431 TI - Quantum-confined Stark effects in CdS1-xSex quantum dots. PMID- 9979432 TI - Heavy- and light-hole band crossing in a variable-strain quantum-well heterostructure. PMID- 9979433 TI - Fluctuations of monatomic steps on Si(001). PMID- 9979434 TI - Fractal aspects related to the Si oxidation process. PMID- 9979435 TI - Raman scattering of the optical vibrational modes in (GaAs)n(AlAs)n superlattices grown on (311)A and (311)B surfaces. PMID- 9979437 TI - Nearly localized states in weakly disordered conductors. PMID- 9979436 TI - Experimental determination of the effect of alloy composition on the band alignment of the CdTe-Cd1-xMnxTe heterojunction. PMID- 9979439 TI - Resonant bipolaron coupling in GaAs quantum wells. PMID- 9979438 TI - Atomic-force microscopy on the Si(111)7 x 7 surface. PMID- 9979440 TI - Conductance of idealized rough channels. PMID- 9979442 TI - Resonant Coulomb screening of charging of a localized state. PMID- 9979441 TI - Multiple-capacitance magnetic-field-dependent Coulomb blockade energetics. PMID- 9979443 TI - Double-tip scanning tunneling microscope for surface analysis. PMID- 9979444 TI - X-ray scattering from rotational disorder in epitaxial films: An unconventional mosaic crystal. PMID- 9979445 TI - X-ray diffraction studies of ordered chloride and bromide monolayers at the Au(111)-solution interface. PMID- 9979447 TI - Melting of A12B Lennard-Jones heteroclusters: A comparative simulation study. PMID- 9979446 TI - Insulating phase of mercury in thin quench-condensed films. PMID- 9979449 TI - Distribution functions and balance equations of drifting Bloch electrons in an electric field. PMID- 9979448 TI - Energetics and atomic steps in the reconstruction of the Pt(110) plane. PMID- 9979450 TI - Reply to "Distribution functions and balance equations of drifting Bloch electrons in an electric field" PMID- 9979451 TI - Comment on "Semimetal-to-semiconductor transition in bismuth thin films" PMID- 9979452 TI - Reply to "Comment on 'Semimetal-to-semiconductor transition in bismuth thin films' " PMID- 9979453 TI - Model for photoinduced anisotropy and its dark relaxation in chalcogenide glasses. PMID- 9979454 TI - Pressure-driven metal-insulator transition in La-doped SmS: Excitonic condensation. PMID- 9979455 TI - Charge-conjugation symmetry breaking and the absorption spectra of polyphenylenes. PMID- 9979456 TI - Cluster-ordered array on the Si(001) surface formed by Al deposition. PMID- 9979458 TI - Quantum magnetotransport theory for bound-state electrons in lateral surface superlattices. PMID- 9979457 TI - Time-resolved photoluminescence of spatially direct and indirect transitions in GaAs /AlxGa1-xAs wires. PMID- 9979459 TI - Electroluminescence spectroscopy in a high magnetic field of the ballistic electron energy distribution in single-barrier heterostructures. PMID- 9979460 TI - Semiclassical quantum percolation in the quantum Hall system. PMID- 9979461 TI - Quantum-dot ground states in a magnetic field studied by single-electron tunneling spectroscopy on double-barrier heterostructures. PMID- 9979462 TI - Structure of the magnetoexciton and optical properties in fractional quantum Hall systems. PMID- 9979464 TI - Electron-electron interactions in one- and three-dimensional mesoscopic disordered rings: A perturbative approach. PMID- 9979463 TI - Energy spectra of anyonic ions and anyonic excitons in fractional quantum Hall systems. PMID- 9979465 TI - Magneto-optical-Kerr-effect study of spin-polarized quantum-well states in a Au overlayer on a Co(0001) ultrathin film. PMID- 9979466 TI - Structural phase transition of K adsorbed on Al(111) investigated using second harmonic generation. PMID- 9979467 TI - Erratum: Electron propagation in orientationally disordered fullerides PMID- 9979469 TI - Determination of the static scaling exponent of self-affine interfaces by nonspecular x-ray scattering. PMID- 9979468 TI - First-principles temperature-pressure phase diagram of magnesium. PMID- 9979470 TI - Two-level-system-related zero-bias anomaly in point-contact spectra. PMID- 9979471 TI - Electronic excitations produced by deep-level promotion during atomic collisions in solids. PMID- 9979472 TI - Quadrupolar effects in the temperature dependence of the lattice parameters of HoP1-xVxO4. PMID- 9979473 TI - Site-selective spectroscopy of erbium-doped SrTiO3, Sr2TiO4, and Sr3Ti2O7. PMID- 9979475 TI - Humidity-dependent structural transition of guanosine and disodium adenosine 5' triphosphate crystals studied by low-frequency Raman spectroscopy. PMID- 9979474 TI - Critical acoustic behavior of the relaxor ferroelectric Na1/2Bi1/2TiO3 in the intertransition region. PMID- 9979476 TI - Birefringence and orientational order in two-component plastic methylchloromethanes. PMID- 9979477 TI - Pressure-induced phase transformations in AlAs: Comparison between ab initio theory and experiment. PMID- 9979478 TI - Charge-exchange processes in titanium-doped sapphire crystals. I. Charge-exchange energies and titanium-bound excitons. PMID- 9979480 TI - Localization, antilocalization, and delocalization in one-dimensional disordered lattices. PMID- 9979479 TI - Charge-exchange processes in titanium-doped sapphire crystals. II. Charge transfer transition states, carrier trapping, and detrapping. PMID- 9979481 TI - Theoretical study of p- and n-type doping of the leucoemeraldine base form of polyaniline: Evolution of the geometric and electronic structure. PMID- 9979482 TI - Local structure in beta -Ti1-yVyHx studied by inelastic neutron scattering. PMID- 9979483 TI - Generalized measures for physical properties of nonperiodic chains. PMID- 9979485 TI - Two-stage melting in two dimensions in a system with dipole interactions. PMID- 9979484 TI - EXAFS and x-ray structural studies of (Tb2O3)0.26(P2O5)0.74 metaphosphate glass. PMID- 9979486 TI - Experimental determination of pair interactions in a Fe0.804V0.196 single crystal. PMID- 9979487 TI - Determination of the atomic structure of disordered systems on the basis of limited Q-space information. PMID- 9979488 TI - Madelung energy for random metallic alloys in the coherent potential approximation. PMID- 9979489 TI - Electrical response of heterogeneous systems of nonlinear inclusions. PMID- 9979490 TI - Phonons in one-dimensional Peierls systems with internal degrees of freedom. PMID- 9979491 TI - Effective mass of helium atoms in one-dimensional microporous channels. PMID- 9979492 TI - Ab initio investigation of the vibrational and geometrical properties of solid C60 and K3C60. PMID- 9979493 TI - Magnetic impurities coupled to quantum antiferromagnets in one dimension. PMID- 9979494 TI - Magnetic structure and spin dynamics of the Pr and Cu in Pr2CuO4. PMID- 9979495 TI - Exact solutions for Ising-model correlations in the 3-12 (extended kagome-acute) lattice. PMID- 9979497 TI - Magnetic and transport measurements on RAuAl (R=La, Ce, and Nd) compounds: Kondo lattice behavior of CeAuAl. PMID- 9979496 TI - Random-field-crossover scaling in Mn0.35Zn0.65F2. PMID- 9979499 TI - Mean-field transfer-matrix study of the magnetic phase diagram of CsNiF3. PMID- 9979498 TI - Large finite-size effect of giant magnetoresistance in magnetic granular thin films. PMID- 9979500 TI - Neutron depolarization in aligned holmium and tests of time-reversal invariance. PMID- 9979502 TI - Collective excitations and screening properties of a condensed charged Bose gas. PMID- 9979501 TI - Polarized XAS studies of ternary nickel oxides. PMID- 9979503 TI - Magnetoplasma resonances and nonlinear mode coupling in pools of ions trapped below the surface of superfluid helium. PMID- 9979505 TI - Two theorems on superconductivity in tight-binding metals. PMID- 9979504 TI - Charge instabilities and phase separation in three-band extended Hubbard models: Effect of O-O hopping. PMID- 9979506 TI - Magnetoinductance of a superconducting Sierpinski gasket. PMID- 9979507 TI - Magnetic oscillations and quasiparticle band structure in the mixed state of type II superconductors. PMID- 9979508 TI - Off-diagonal interactions, Hund's rules, and pair binding in C60. PMID- 9979510 TI - Simple model for the dc flux transformer in layered superconductors with Josephson coupling. PMID- 9979509 TI - Normal-state electronic Raman-scattering efficiencies of YBa2Cu3O7- delta, Bi2Sr2CaCu2O8, and Tl2Ba2Ca2Cu3O10: Effects of local-density-approximation Fermi surface mass fluctuations. PMID- 9979511 TI - Hall effect in type-II superconductors. PMID- 9979513 TI - Mobility of electrons in a quasi-one-dimensional conducting channel on the liquid helium surface. PMID- 9979512 TI - Short-range antiferromagnetic orientational correlations in Rb3C60. PMID- 9979514 TI - Liaison between superconductivity and phase separation. PMID- 9979516 TI - Analysis of pinning effects in YBa2Cu3O7- delta single crystals after fast neutron irradiation. PMID- 9979515 TI - Magnetic susceptibility and low-temperature structure of the linear chain cuprate Sr2CuO3. PMID- 9979517 TI - Vortex lattices in layered superconductors. PMID- 9979519 TI - Positron trapping in Y1-xPrxBa2Cu3O7- delta and the Fermi surface of YBa2Cu3O7- delta. PMID- 9979518 TI - Phonon anomalies in a-axis-oriented (YBa2Cu3O7)m(PrBa2Cu3O7)n superconducting superlattices: Evidence for an anisotropic gap function. PMID- 9979520 TI - Reversible magnetization, critical fields, and vortex structure in grain-aligned YBa2Cu4O8. PMID- 9979521 TI - Hole pockets in the t-J model. PMID- 9979522 TI - Nonlinear supercurrent response in anisotropic superconductors. PMID- 9979523 TI - Impurity effects in d-wave superconductors. PMID- 9979524 TI - Superconducting Tc for a model spin-fluctuation spectrum with four sharp peaks in the corners of the Brillouin zone. PMID- 9979525 TI - Hole-hole superconducting pairing in the t-J model induced by spin-wave exchange. PMID- 9979526 TI - Accumulated photon echo in neodymium-doped disordered yttrium fluoride crystals. PMID- 9979527 TI - Periodic surface instabilities in stressed polymer solids. PMID- 9979528 TI - Surface magnetization and critical behavior of a hierarchical quantum Ising chain. PMID- 9979530 TI - Dynamical scaling from multiscale measurements. PMID- 9979529 TI - Field-induced localization in Fibonacci and Thue-Morse lattices. PMID- 9979531 TI - Charge Kosterlitz-Thouless transition in thin granular films due to charge confinement. PMID- 9979532 TI - Superconducting transition in two bidimensional t-J lattices with interplane single-electron hopping. PMID- 9979533 TI - In-plane electrical resistivity of La2-xSrxCuO4 at constant volume. PMID- 9979535 TI - Complex resistivity of the mixed state in high-Tc superconductors with random and regular pinnings. PMID- 9979534 TI - Scaling of the normal-state transport properties of underdoped YBa2Cu3Ox. PMID- 9979536 TI - Vortex-lattice structure in layered superconductors. PMID- 9979537 TI - Effects of electron correlation in crystal-field splittings of Sm2+ in MFCl-type hosts. PMID- 9979538 TI - Fluctuations of the number of energy levels at the mobility edge. PMID- 9979540 TI - Oscillatory exchange coupling with a period of two Fe monolayers in Au/Fe/Au/Fe/Au(001). PMID- 9979539 TI - Effect of crystal size reduction on lattice symmetry and cooperative properties. PMID- 9979541 TI - Dependence of giant magnetoresistance on oxygen stoichiometry and magnetization in polycrystalline La0.67Ba0.33MnOz. PMID- 9979543 TI - Direct calculation of the spin stiffness in the J1-J2 Heisenberg antiferromagnet. PMID- 9979542 TI - Ultrasonic study of the magnetic phase diagram of the spin-Peierls system CuGeO3. PMID- 9979544 TI - Unusual electronic structure near EF in the organic superconductor kappa - PMID- 9979546 TI - Resistance scaling at the Kosterlitz-Thouless transition. PMID- 9979545 TI - Nuclear spin-lattice relaxation and antiferromagnetic spin correlations in superconducting thiospinel Cu1.5Co1.5S4. PMID- 9979547 TI - Multiplet effects in the quasiparticle band structure of the f1-f2 Anderson model. PMID- 9979549 TI - Thermopower of the superconducting cuprates. PMID- 9979548 TI - Magnetothermal conductivity of Ba1-xKxBiO3 crystals. PMID- 9979550 TI - Low-temperature increase of resistive critical fields in certain superconductors: A simple fluctuation approach. PMID- 9979551 TI - Erratum: Magnetocaloric approach to type-II superconductors PMID- 9979552 TI - Erratum: Editorial Note: Inner-space reconstruction of quasicrystal structure factors PMID- 9979553 TI - Reentrant structural phase transitions induced by external magnetic fields in TmxLu1-xPO4 and TbxY1-xVO4 crystals. PMID- 9979554 TI - Electronic and structural properties of alkaline-earth oxides under high pressure. PMID- 9979556 TI - Temperature variation of the ESR parameters of the self-trapped-electron center in PbCl2. PMID- 9979555 TI - Orthogonal strains and onset of plasticity in shocked LiF crystals. PMID- 9979557 TI - Nonlinear excitation of capillary waves by the Marangoni motion induced with a modulated laser beam. PMID- 9979559 TI - Arrival times for dissipative, nonlinear second-sound waves in solids. PMID- 9979558 TI - Photoconductivity in n-type beta -FeSi2 single crystals. PMID- 9979561 TI - In-plane resistivity from a two-dimensional t-J model. PMID- 9979560 TI - Theoretical analysis of the thermal conductivity of diamond in a two-step model. PMID- 9979563 TI - Variational analyses of series expansions of the Potts model. PMID- 9979562 TI - Ferromagnetic Kondo lattice behavior in CeNiSb. PMID- 9979564 TI - Frequency and temperature dependence of the transport relaxation rate of the Kondo alloy U0.2Y0.8Pd3: Evidence for non-Fermi-liquid behavior. PMID- 9979565 TI - Self-consistent three-pole approximation study of the spin dynamics in two dimensional antiferromagnetic Heisenberg paramagnets. PMID- 9979566 TI - Crossover from extensive to nonextensive behavior driven by long-range interactions. PMID- 9979567 TI - Muon-spin-relaxation studies on the heavy-fermion system with non-Fermi-liquid behavior CeCu5.9Au0.1. PMID- 9979568 TI - Pair model of magnetostriction for hexagonal close-packed crystals. PMID- 9979569 TI - Temporal response of the thermal boundary resistance in superfluid helium. PMID- 9979570 TI - Flux-flow fingerprint of disorder: Melting versus tearing of a flux-line lattice. PMID- 9979571 TI - Lower critical field of YNi2B2C and the influence of granularity. PMID- 9979572 TI - Evidence of unusual hybridization: Electrical resistivity and specific heat of Y1 xTbxBa2Cu3O7 single crystals. PMID- 9979573 TI - Observation of magnetic-field penetration via dendritic growth in superconducting niobium films. PMID- 9979574 TI - Nonlocal interaction in a system of Josephson junctions. PMID- 9979575 TI - XPS study of the O 1s spectra of (Bi,Pb)2Sr2CaCu2Ox and Bi2Sr2CaCu2Ox high-Tc superconductors. PMID- 9979576 TI - Charge distribution in Y1-xPrxBa2Cu3O7: A valency model for the depression of Tc. PMID- 9979577 TI - Magnetic susceptibility studies on PrxY1-xBa2Cu3O7- delta single crystals in the insulating regime. PMID- 9979578 TI - Imaging of electromagnetic resonances in a YBa2Cu3O7- delta bicrystal grain boundary Josephson junction. PMID- 9979579 TI - Interpretation of the oblique Abrikosov flux lattice in YBa2Cu3O7. PMID- 9979580 TI - Lattice-embedded multiconfigurational self-consistent-field calculations of the Mn-perturbed F-center defect in CaF2:Mn. PMID- 9979581 TI - Molecular-dynamics simulation of fragmentation of C60 colliding with H2. PMID- 9979582 TI - X-ray powder diffraction from carbon nanotubes and nanoparticles. PMID- 9979583 TI - In situ nuclear magnetic resonance investigation of deformation-generated vacancies in aluminum. PMID- 9979584 TI - Determination of triple points in the phase diagram of praseodymium. PMID- 9979585 TI - Role of PMID- 9979586 TI - Magnetic-field response of the interphase boundary dynamics in perovskite solid solutions. PMID- 9979587 TI - Anharmonicity effects on the extended x-ray-absorption fine structure: The case of beta -AgI. PMID- 9979588 TI - Efficient effective-energy method for lattice-Green's-function simulations of fracture. PMID- 9979589 TI - Anharmonic contribution to the Debye-Waller factor for copper, silver, and lead. PMID- 9979590 TI - Sharp line emission of KZnF3:Cr3+ PMID- 9979591 TI - Site-selective laser spectroscopy of Mo3+ in phosphate glass. PMID- 9979592 TI - First-principles investigations of atomic disorder effects on magnetic and structural instabilities in transition-metal alloys. PMID- 9979593 TI - Statistical and transport properties of quasiperiodic layered structures: Thue Morse and Fibonacci. PMID- 9979594 TI - Unstable periodic orbits and characterization of the spatial chaos in a nonlinear monatomic chain at the T=0 first-order phase-transition point. PMID- 9979595 TI - Dense branched growth of (SCN)x and ion transport in the poly(ethyleneoxide) NH4SCN polymer electrolyte. PMID- 9979596 TI - Effects of nonlinearity on the time evolution of single-site localized states in periodic and aperiodic discrete systems. PMID- 9979597 TI - Frequency moments of the spectral density of an atomic-displacement time correlation function of a three-dimensional Lennard-Jones crystal in the classical and quantum regimes. PMID- 9979598 TI - Thermal conductivity of sputtered oxide films. PMID- 9979599 TI - Numerical simulations of aerogel sintering. PMID- 9979600 TI - Dissipation function of the first-order phase transformation in solids via internal-friction measurements. PMID- 9979602 TI - Exact property of the autocorrelation function of a conserved spin component. PMID- 9979601 TI - Dissipation function of the first-order phase transformation in VO2 ceramics by internal-friction measurements. PMID- 9979603 TI - Spin-glass-like ordering of the magnetic moments of interacting nanosized maghemite particles. PMID- 9979605 TI - Spin correlations in low-dimensional spin-1/2 antiferromagnets. PMID- 9979604 TI - Spectroscopic study of the electronic states of single-crystal CuGeO3. PMID- 9979607 TI - Anisotropic Heisenberg ferromagnetic model in two dimensions. PMID- 9979606 TI - Magnetic properties of the Gd(Ni1-xCox)2B2C series: Macroscopic and microscopic studies. PMID- 9979608 TI - Ferromagnetic coupling in nonmetallic Cu2+ compounds. PMID- 9979609 TI - Magnetic studies of some orthovanadates. PMID- 9979610 TI - Influence of spin-orbit coupling on the transport and magnetic properties of Co3Pd97. PMID- 9979611 TI - Temperature dependence of the giant magnetoresistance in Ni-Co/Cu, Ni-Fe/Cu, and Co-Fe/Cu multilayer films. PMID- 9979612 TI - Brillouin scattering in Co/Cu/Co and Co/Au/Co trilayers: Anisotropy fields and interlayer magnetic exchange. PMID- 9979613 TI - Role of interfacial roughness in the giant magnetoresistance in Co/Cu superlattices. PMID- 9979614 TI - Cavity-fields approach to quadrupolar glass. PMID- 9979615 TI - Static and dynamical properties of a magnetic impurity in a strongly correlated electronic system. PMID- 9979616 TI - Ultrasonic study of the magnetic phase diagrams of CsNi0.98M0.02Cl3 (M=Co, Fe, Mg). PMID- 9979617 TI - Landau theory of quantum spin glasses of rotors and Ising spins. PMID- 9979618 TI - Theory of interlayer magnetic coupling. PMID- 9979619 TI - Confinement of spinons in the CPM-1 model. PMID- 9979620 TI - Magnetic profiles of compositionally tailored Permalloy-copper films: A theoretical and experimental comparison. I. Growth and stoichiometric characterization using scanning Auger microscopy. PMID- 9979621 TI - Magnetic profiles of compositionally tailored Permalloy-copper films: A theoretical and experimental comparison. II. Spin-wave resonance. PMID- 9979622 TI - Oxygen dependence of the crystal structure of HgBa2CuO4+ delta and its relation to superconductivity. PMID- 9979623 TI - High-field fluctuations of a kappa -(BEDT-TTF)2Cu PMID- 9979624 TI - Interactions of collective excitations with vortices in superfluid systems. PMID- 9979626 TI - Quasiparticle spectrum around a vortex line in a d-wave superconductor. PMID- 9979625 TI - Structural and electronic properties of (NH3)xK3C60. PMID- 9979628 TI - High-frequency pumping of Josephson soliton oscillators. PMID- 9979627 TI - Some consequences of flux avalanches in type-II superconductors. PMID- 9979629 TI - Spatiotemporal chaos in rf-driven Josephson junction series arrays. PMID- 9979631 TI - Thermal expansion of V3Si with controlled martensite-phase morphology. PMID- 9979630 TI - Excitation spectrum of a type-II superconductor in a very high magnetic field with randomly pinned vortices. PMID- 9979632 TI - Exact scaling relations in one- and two-dimensional Luttinger liquids: Competition between superconductivity and antiferromagnetism. PMID- 9979633 TI - Muon-spin-rotation studies of the temperature dependence of the magnetic penetration depth in the YBa2Cu3Ox family and related compounds. PMID- 9979635 TI - Two different thermally activated flux-flow regimes in oxygen-deficient YBa2Cu3O7 x thin films. PMID- 9979634 TI - Electronic structure as a function of doping in YBa2Cu3Ox(6.2 <= x <= 6.9) studied by angle-resolved photoemission. PMID- 9979636 TI - Penetration depth in YBa2Cu3O7 thin films from far-infrared transmission. PMID- 9979637 TI - Unconventional lattice stiffening in superconducting La2-xSrxCuO4 single crystals. PMID- 9979638 TI - Analysis of the nonequilibrium photoresponse of superconducting films to pulsed radiation by use of a two-temperature model. PMID- 9979639 TI - Temperature-dependent tunneling spectra of Bi2Sr2CaCu2O8 single crystals with well-defined Bi2Sr2CuO6 epitaxial layers. PMID- 9979640 TI - Raman electronic continuum in a spin-fluctuation model for superconductivity. PMID- 9979641 TI - Phenomenological models for the gap anisotropy of Bi2Sr2CaCu2O8 as measured by angle-resolved photoemission spectroscopy. PMID- 9979642 TI - Interlayer vortices and edge dislocations in high-temperature superconductors. PMID- 9979644 TI - Spin-charge separation in the t-J model: Magnetic and transport anomalies. PMID- 9979643 TI - Effect of the three-site hopping term on the t-J model. PMID- 9979645 TI - Charge transport in junctions between d-wave superconductors. PMID- 9979647 TI - Hydroxyl defects in germanium-doped quartz: Defect dynamics and radiation effects. PMID- 9979646 TI - Phase transformation of BeSe and BeTe to the NiAs structure at high pressure. PMID- 9979648 TI - Grain-boundary atomic structure in nanocrystalline palladium from x-ray atomic distribution functions. PMID- 9979649 TI - Relationship between OH- defect reorientation rates and the quenching of the F center luminescence in alkali halides. PMID- 9979650 TI - Photochromic centers and impurities in nominally pure KTaO3 and K1-xLixTaO3. PMID- 9979651 TI - Neutron-scattering study of interfacial roughening in twinned orthorhombic Dy(As0.15V0.85)O4. PMID- 9979652 TI - Face-centered-cubic to orthorhombic phase transition in single-crystal RbC60 analyzed by Raman scattering. PMID- 9979653 TI - Intrinsic ductility criterion for interfaces in solids. PMID- 9979654 TI - Movement of the interphase boundary in KNbO3 under pressure. PMID- 9979655 TI - Neutron-scattering study of pretransitional dynamics in the deuterated diacetylene monomer 2,4-hexadiynylene bis(p-toluenesulfonate). PMID- 9979657 TI - Critical behavior of hierarchical Ising models. PMID- 9979656 TI - Photoemission investigation of the electronic-structure changes in Zr-Ni-Cu metallic glasses upon hydrogenation. PMID- 9979658 TI - Near-infrared dynamics of photoexcitations in a substituted polyacetylene. PMID- 9979659 TI - Evidence of amorphization in molecular-dynamics simulations on irradiated intermetallic NiAl. PMID- 9979660 TI - Acoustic properties of oxide glasses at low temperatures. PMID- 9979661 TI - Glass transition in a Fredrickson-Anderson model with chemical reactions. PMID- 9979663 TI - Microscopic mechanisms for kinetic friction: Nearly frictionless sliding for small solids. PMID- 9979662 TI - Gradual freezing of orientational degrees of freedom in cubic Ar1-x(N2)x mixtures. PMID- 9979664 TI - Thermal conductivity and accommodation coefficient of spin-polarized atomic hydrogen gas. PMID- 9979665 TI - Common interatomic potential model for the lattice dynamics of several cuprates. PMID- 9979666 TI - Diffusion of atoms and molecules in the solid hydrogens. PMID- 9979668 TI - Magnetic properties of disordered Ising systems with various probability distributions of the exchange integrals. PMID- 9979667 TI - Three-dimensional antiferromagnetic transition of iodine-doped fluoro-aluminum phthalocyanine with a disordered polymer chain. PMID- 9979669 TI - Crystal structures and low-temperature behaviors of the heavy-fermion compounds CeRuGe3 and Ce3Ru4Ge13 containing both trivalent and tetravalent cerium. PMID- 9979670 TI - Ferromagnetic and freezing transitions in electron liquids: Exchange and Coulomb effects at finite temperatures. PMID- 9979671 TI - Inergodicity and dynamical phase transitions in the soft spherical spin-glass model. PMID- 9979673 TI - High-intensity gamma -ray scattering from alkali halide crystals. PMID- 9979672 TI - Role of applied transverse field in a ferrimagnetic bilayer system with disordered interfaces. PMID- 9979674 TI - Perpendicular magnetic anisotropy, domains, and misfit strain in epitaxial Ni/Cu1 xNix/Cu/Si (001) thin films. PMID- 9979675 TI - High magnetic fields and the correlation gap in SmB6. PMID- 9979676 TI - Ce5Ni6In11: An intermediate heavy-fermion system. PMID- 9979677 TI - Staggered magnetization in La2-xSrxCuO4 from 139La NQR and microSR: Effects of Sr doping in the range 0(3 x 3)-->(4 x 4) formed on Cu(001) with increasing Li coverage. PMID- 9980296 TI - Intermolecular charge-transfer excitation in C60 films: Evidence from luminescence and photoconductivity. PMID- 9980295 TI - Electronic states and stability of the insulating RbC60 dimer phase. PMID- 9980297 TI - Clean-surface study of stage-1 alkali-metal graphite intercalation compounds by scanning tunneling microscopy. PMID- 9980298 TI - Unusual surfactant effect and the stability of pseudomorphic gamma -Fe films. PMID- 9980299 TI - Semiempirical model for the electrical properties of La1-xCaxCoO3. PMID- 9980300 TI - Electronic structure of the lead monoxides: Band-structure calculations and photoelectron spectra. PMID- 9980301 TI - Absorption-edge singularities for a nonequilibrium Fermi sea. III. Determinantal nonperturbative theory. PMID- 9980302 TI - Electronic structure of stoichiometric and Ar+-bombarded ZrO2 determined by resonant photoemission. PMID- 9980304 TI - Near-edge x-ray-absorption fine structure of crystalline silicon dioxides. PMID- 9980303 TI - Dynamic and static structure factor of electrons in Si: Inelastic x-ray scattering results. PMID- 9980305 TI - Electronic structure of beta -PbO2 and its relation with BaPbO3. PMID- 9980307 TI - Low-energy properties of the two-dimensional Hubbard model near half filling. PMID- 9980306 TI - Metallic photonic band-gap materials. PMID- 9980308 TI - Spin-dependent Mn K-edge XANES of MnO and MnF2: Full multiple-scattering analysis. PMID- 9980309 TI - Optical studies of the growth of Cd1-xZnxS nanocrystals in borosilicate glass. PMID- 9980310 TI - eta mechanism and Berry's phase in the Hubbard model with a long-range interaction. PMID- 9980311 TI - Energy transport in photoexcited crystals of K3 PMID- 9980312 TI - Ab initio pseudopotential calculations of the atomic and electronic structure of the Ta (100) and (110) surfaces. PMID- 9980313 TI - Chemical hardness, linear response, and pseudopotential transferability. PMID- 9980315 TI - Correlation energy functionals for ab initio calculations: Application to transition metals. PMID- 9980314 TI - Electronic structure and valence-band spectra of Bi4Ti3O12. PMID- 9980316 TI - Ab initio calculation of the optical and photoelectron properties of RuO2. PMID- 9980317 TI - Electronic structure of cuprates containing sulfur and phosphorus oxyanions. PMID- 9980318 TI - Stability, chemical bonding, and vibrational properties of amorphous carbon at different mass densities. PMID- 9980319 TI - Coexistence of short- and large-scale phase variations in a charge-density wave weakly coupled to impurities. PMID- 9980320 TI - Resonant photoemission study on the boron 1s exciton of the wide-band-gap semiconductor c-BN. PMID- 9980322 TI - Si K, Si L, and Cr K x-ray valence-band studies of bonding in chromium silicides: Experiment and theory. PMID- 9980321 TI - Vibrational spectroscopy of group-II-acceptor-hydrogen complexes in GaP. PMID- 9980323 TI - 11B NMR and relaxation study of boron nitride. PMID- 9980325 TI - First-principles study of DX centers in CdTe, ZnTe, and CdxZn1-xTe alloys. PMID- 9980324 TI - Nonradiative recombination processes in nickel- and iron-doped ZnS and ZnSe studied by photoinduced electron-spin resonance. PMID- 9980326 TI - Effect of the image potential on excitons in semi-infinite semiconductors. PMID- 9980328 TI - Electronic charge distribution in crystalline germanium. PMID- 9980327 TI - Structure and visible photoluminescence of porous Si1-xGex. PMID- 9980329 TI - First-principles study of phosphorus and nitrogen impurities in ZnSe. PMID- 9980330 TI - Outgoing excitonic resonance in multiphonon Raman scattering from polar semiconductors. PMID- 9980331 TI - Use of zinc diffusion into GaAs for determining properties of gallium interstitials. PMID- 9980332 TI - Surface electronic and atomic structure of ErSi1.7 on Si(111). PMID- 9980334 TI - Static and dynamic correlation functions of a two-dimensional quantum electron fluid. PMID- 9980333 TI - Mesoscopic ring under the influence of time-periodical flux: Aharonov-Bohm oscillations and transmission of wave packets. PMID- 9980336 TI - InAs/GaAs pyramidal quantum dots: Strain distribution, optical phonons, and electronic structure. PMID- 9980335 TI - Optical intersubband transitions in conduction-band quantum wells. PMID- 9980337 TI - Hydrogenic impurity levels, dielectric constant, and Coulomb charging effects in silicon crystallites. PMID- 9980338 TI - Electron mobility in two-dimensional modulation-doped In1-xAlxAs/In1-yGayAs alloy systems. PMID- 9980339 TI - Performance of correlation functionals in ab initio chemisorption cluster-model calculations: Alkali metals on Si(111). PMID- 9980340 TI - Effect of ion bombardment on deep photoluminescence bands in p-type boron modulation-doped Si layers grown by molecular-beam epitaxy. PMID- 9980341 TI - Excitonic absorption in CdTe-based piezoelectric quantum wells. PMID- 9980342 TI - Identification of surface core-level shift origin for prototypical Cs/Si(100) 2 x 1 system by photoemission EXAFS. PMID- 9980343 TI - Exciton s states in semiconductor quantum wells in a magnetic field. PMID- 9980345 TI - InAsSb/InAs: A type-I or a type-II band alignment. PMID- 9980344 TI - Exciton magnetic polarons in short-period CdTe/Cd1-xMnxTe superlattices. PMID- 9980346 TI - Wave-packet dynamics in quantum wells. PMID- 9980347 TI - Photoelectric emission from negative-electron-affinity diamond (111) surfaces: Exciton breakup versus conduction-band emission. PMID- 9980348 TI - Structural and physical properties of mercury-iron selenide layers and quantum wells. PMID- 9980349 TI - Ballistic-electron-emission microscopy of strain nonuniformities in Si1-xGex/Si structures. PMID- 9980350 TI - Spin-split cyclotron resonance and spatial distribution of interacting electrons. PMID- 9980351 TI - Initial- and final-state effects in the conduction bands of 2H-MoS2(0001) studied by k||-resolved inverse photoemission spectroscopy. PMID- 9980352 TI - Evidence for quantum confinement in porous silicon from photoluminescence measurements. PMID- 9980353 TI - Band structure and electro-optical properties of mixed type-I/type-II InxGa1 xAs/InyGa1-yAs superlattices. PMID- 9980354 TI - Hexagonal crystallization in a two-dimensional electron gas with disorder. PMID- 9980355 TI - Resonant tunneling in the presence of a two-level fluctuator: Low-frequency noise. PMID- 9980356 TI - Screening in clean mesoscopic rings. PMID- 9980357 TI - Density-functional theory of quantum wires and dots in a strong magnetic field. PMID- 9980358 TI - Direct and indirect magnetoexcitons in symmetric InxGa1-xAs/GaAs coupled quantum wells. PMID- 9980359 TI - Optical properties of Sb-terminated GaAs and InP (110) surfaces. PMID- 9980360 TI - Photoconductance oscillations in a two-dimensional quantum point contact. PMID- 9980361 TI - Observation of the formation of a carbon-rich surface layer in silicon. PMID- 9980363 TI - Semiclassical theory of the perpendicular magnetoresistance in superlattices. PMID- 9980362 TI - Theory of direct creation of quantum-well excitons by hole-assisted electron resonant tunneling. PMID- 9980364 TI - Conductance of a quantum dot with a Hubbard interaction in the presence of a boson field. PMID- 9980365 TI - Roughness of heterointerfaces and averaging effects by excitons: Interpretation of cathodoluminescence images. PMID- 9980366 TI - Electronic subband structure of InP/InxGa1-xP quantum islands from high-pressure photoluminescence and photoreflectance. PMID- 9980367 TI - Magnetotransport in a pseudomorphic GaAs/Ga0.8In0.2As/Ga0.75Al0.25As heterostructure with a Si delta -doping layer. PMID- 9980369 TI - Exact effective-mass theory for heterostructures. PMID- 9980368 TI - Energy band structure and linear optical properties of Si and Ge strained along the PMID- 9980370 TI - Foundations of the envelope-function theory for phonons in heterostructures. PMID- 9980371 TI - Wigner-crystal states for the two-dimensional electron gas in a double-quantum well system. PMID- 9980372 TI - Wigner-crystal phases in bilayer quantum Hall systems. PMID- 9980373 TI - Quantum versus semiclassical treatment of multiphonon effects in He-atom scattering from surfaces. PMID- 9980374 TI - Faceting and reconstruction of stepped Au(111). PMID- 9980375 TI - Ab initio study of local d-d excitations in bulk CoO, at the CoO(100) surface, and in octahedral Co2+ complexes. PMID- 9980377 TI - Core-level satellite excitations of K/Al(100) and K/Al(111). PMID- 9980378 TI - Origin of the vibrational shift of CO chemisorbed on Pt(111). PMID- 9980376 TI - Second-harmonic generation in centrosymmetric molecular films: Analysis under anisotropic conditions. PMID- 9980380 TI - Synchrotron-radiation-stimulated evaporation and defect formation in a-SiO2. PMID- 9980379 TI - Structural determination of a W(001)c(2 x 2)-Ag surface by x-ray photoelectron diffraction with multiple-scattering analysis. PMID- 9980381 TI - Energy and lifetime of the sigma resonance of oriented O2 physisorbed on Ag(110). PMID- 9980382 TI - Positron dynamics in surface-charged solid argon. PMID- 9980383 TI - Dynamical effective potentials in electron tunneling: Path-integral study. PMID- 9980384 TI - Indirect bulk plasmon generation by electrons reflected above the solid surface. PMID- 9980385 TI - Bonding mechanism at bimetallic interfaces: Pd overlayer on various substrates. PMID- 9980386 TI - Dispersion-force effects in interfacial premelting of ice. PMID- 9980387 TI - Universality of the scaling exponents for the T=0 conductivity and Hall coefficient for very weakly compensated barely metallic silicon. PMID- 9980388 TI - Response to "Universality of the scaling exponents for the T=0 conductivity and Hall coefficient for very weakly compensated barely metallic silicon" PMID- 9980389 TI - Comment on "Suppression of conductance fluctuations in short one-dimensional conductors" PMID- 9980390 TI - Scanning tunneling microscopy: Energetics from statistical analysis. PMID- 9980391 TI - Kinetics of the first-order phase transition in CuAu from atomistic Landau theory. PMID- 9980392 TI - Measurement and interpretation of nonuniversal critical exponents in disordered conductor-insulator composites. PMID- 9980393 TI - Heat transport and nonthermal excitations in vibrational hopping systems. PMID- 9980394 TI - Rigorous results on a first-order phase transition in antiferromagnetic spin-1/2 coupled chains. PMID- 9980395 TI - Frustrated spin-1/2 model in two dimensions with columnar dimer states as possible ground states. PMID- 9980397 TI - Magnetic, nonmagnetic, and non-Fermi-liquid ground state of an impurity fluctuating between two magnetic configurations. PMID- 9980396 TI - Commensurate and modulated magnetic phases in orthorhombic AC60 (A=K,Rb). PMID- 9980398 TI - Violation of universality for Ising spin-glass transitions. PMID- 9980399 TI - Theory of circular dichroism in photon STM experiments on magnetic samples. PMID- 9980400 TI - Hidden order and symmetry breaking in the ground state of a spin-1/2 antiferromagnetic Heisenberg ladder. PMID- 9980401 TI - Finite-size scaling study of the vortex-free three-dimensional XY model. PMID- 9980402 TI - Interlayer magnetic coupling of multilayer structures with palladium spacer layers. PMID- 9980403 TI - 17O NQR study of glass order in Rb0.5(NH4)0.5H2PO4. PMID- 9980405 TI - Sublattice switching in the three-dimensional ordered phase of the triangular lattice antiferromagnet CsCoCl3. PMID- 9980404 TI - Structure dependence of the ferromagnetic transition temperature in rhombohedral La1-xAxMnO3 (A=Na, K, Rb, and Sr). PMID- 9980407 TI - Self-consistent Born approximation for the hole motion in the three-band model: A comparison with photoemission experiments. PMID- 9980406 TI - Absence of a substrate state for 3He in a 3He-4He bulk mixture in proximity to a strong-binding surface. PMID- 9980408 TI - Self-consistent study of the Josephson effect for the d-wave superconductor insulator-superconductor junction. PMID- 9980410 TI - Pressure coefficient of the superconducting transition temperature within the van Hove scenario. PMID- 9980409 TI - Frequency dependence of the local ac magnetic response in type-II superconductors. PMID- 9980411 TI - Angle-resolved photoemission spectroscopy study of Bi2Sr2CaCu2O8+ delta thin films. PMID- 9980412 TI - IcRn product in c-axis Josephson junctions involving high-temperature superconductors. PMID- 9980413 TI - van Hove singularity scenario and hole density in CaCuO2: Pressure effects. PMID- 9980414 TI - Structure and energetics of antiferroelectric PbZrO3. PMID- 9980415 TI - Morphology, structure, and growth of nanoparticles produced in a carbon arc. PMID- 9980416 TI - Theory of structural, electronic, vibrational, and superconducting properties of high-pressure phases of sulfur. PMID- 9980418 TI - Raman and birefringence studies of the low-temperature phase transitions in LiK1 xRbxSO4 crystals. PMID- 9980417 TI - Structure-stability relationships for all-silica structures. PMID- 9980419 TI - Order-disorder transition at the (001) surface of a 3 at. %-Au-rich Cu3Au crystal. PMID- 9980420 TI - Structure of helium and neon in zeolite. PMID- 9980421 TI - Nephelauxetic effects on Sm2+ and Eu3+ in ternary MYX compounds. PMID- 9980423 TI - Equation-of-state behavior for different phases of lead under strong compression. PMID- 9980422 TI - Mechanical instabilities of homogeneous crystals. PMID- 9980424 TI - Slowing down of 3-eV Sm ions in Eu compounds. PMID- 9980425 TI - Statistics of avalanches in martensitic transformations. I. Acoustic emission experiments. PMID- 9980426 TI - Statistics of avalanches in martensitic transformations. II. Modeling. PMID- 9980427 TI - Magnetic-resonance measurements on the 5A2 excited state of the neutral vacancy in diamond. PMID- 9980428 TI - Spectroscopic studies and crystal-field analysis of Cm3+ and Gd3+ in LuPO4. PMID- 9980429 TI - Two-photon spectroscopy between states of opposite parities. PMID- 9980430 TI - NMR pressure study of 27Al and 65Cu in the Al65Cu20Ru15 quasicrystal. PMID- 9980431 TI - Anomalous electrical resistivities of decagonal approximants. PMID- 9980432 TI - Model of vitreous SiO2 generated by an ab initio molecular-dynamics quench from the melt. PMID- 9980433 TI - Ordering process in the induction period of crystallization of poly(ethylene terephthalate). PMID- 9980435 TI - Exact self-energy of the many-body problem from conserving approximations. PMID- 9980434 TI - Nondissipative fluctuator splitting renormalization and its magnetic field tuning. PMID- 9980436 TI - Vertex function for the coupling of an electron with intramolecular phonons: Exact results in the antiadiabatic limit. PMID- 9980437 TI - Evolution and stability of self-localized modes in a nonlinear inhomogeneous crystal lattice. PMID- 9980438 TI - Formation of large bipolarons. PMID- 9980440 TI - Degenerate helix spin configuration supported by three-site biquadratic exchange. PMID- 9980441 TI - Ab initio optimized pseudopotential calculations of magnetic systems. PMID- 9980439 TI - Observation of magnetization saturation of CuGeO3 in ultrahigh magnetic fields up to 500 T. PMID- 9980442 TI - Analytic calculation of the spin sum rule at the L2,3 edges of Cu2+ PMID- 9980443 TI - Photoacoustic investigation of the temperature and magnetic-field dependence of the specific-heat capacity and thermal conductivity near the Curie point of gadolinium. PMID- 9980444 TI - Superparamagnetic relaxation of Fe deposited on MgO(001). PMID- 9980446 TI - First-order valence phase transition in CeNi1-xCoxSn alloys. PMID- 9980445 TI - Magnetic behavior of the heavy-fermion system UPd2Ga3. PMID- 9980447 TI - Gaussian critical regime and specific-heat amplitude ratio in dipolar ferromagnets. PMID- 9980449 TI - Spin dynamics and spin-polarized EELS spectra of model itinerant-electron magnetic films. PMID- 9980448 TI - Correlation between structure and magnetic behavior of Fe-P amorphous alloys. PMID- 9980450 TI - Extended solubility and spin-glass behavior in a Ag-Gd solid solution prepared by mechanical alloying. PMID- 9980451 TI - Phase stability and low-temperature specific heat up to 14 T of BaCuOx as a function of oxygen stoichiometry. PMID- 9980452 TI - Edge states in open antiferromagnetic Heisenberg chains. PMID- 9980453 TI - Low-temperature two-dimensional order-disorder magnetic transition in TbRu2Si2 within a square-modulated magnetic phase. PMID- 9980455 TI - Response of superconductive films to localized energy deposition. PMID- 9980454 TI - Ginzburg-Landau theory of vortex lattice structure in deformable anisotropic superconductors. PMID- 9980457 TI - Peltier effect in normal-metal-superconductor microcontacts. PMID- 9980456 TI - Sound transmission phenomena and phase-separation kinetics at the superfluid normal interface of liquid 3He-4He mixtures. PMID- 9980458 TI - Spiral fluxons and a characteristic frequency in two-dimensional Josephson junctions. PMID- 9980460 TI - Characterization of low-temperature electronic states of the organic conductors alpha -(BEDT-TTF)2MHg(SCN)4 (M=K, Rb, and NH4) by specific-heat measurements. PMID- 9980459 TI - Electron-spin-resonance studies of the hole-doping effect on (Tl0.5Pb0.5)Sr2(Ca1 xYx)Cu2O7 high-Tc superconductors. PMID- 9980461 TI - Investigation of the dB/dH effect using trapped flux in type-II superconductors. PMID- 9980463 TI - Electronic structure and phase-stability studies on superconducting YNi2B2C, YRh3B, and nonsuperconducting YNi4B. PMID- 9980462 TI - Perturbation of tunneling processes by mechanical degrees of freedom in mesoscopic junctions. PMID- 9980464 TI - Reversible and irreversible magnetization of the Chevrel-phase superconductor PbMo6S8. PMID- 9980465 TI - Elastic chain in a random potential: Simulation of the displacement correlation function and relaxation. PMID- 9980466 TI - First-principles calculation of the electronic and optical properties of the organic superconductor kappa -(BEDT-TTF)2Cu(NCS)2. PMID- 9980468 TI - Superconductivity in the Van Vleck metals. PMID- 9980467 TI - Quantum smectic and supersolid order in helium films and vortex arrays. PMID- 9980469 TI - Two-hole bound states in a modified t-J model. PMID- 9980471 TI - Hall effect and flux dynamics in YBa2Cu3O7/PrBa2Cu3O7 multilayers in the mixed state. PMID- 9980470 TI - Relationship between superconductor and metal-insulator transitions in a large class of tetragonal 1:2:3 cuprates Ca-R-Ba-Cu-O (R=La,Nd). PMID- 9980472 TI - Raman spectrum of Pr2CuO4: Crystal-field transitions of Pr3+ and the A* mode. PMID- 9980474 TI - Flux-diffusion-induced anomalies in the field-cooled magnetization of high temperature superconductors. PMID- 9980473 TI - Structural, magnetic, and heat-capacity studies on Zn- and Ga-substituted PrBa2Cu3O7- delta. PMID- 9980475 TI - Temperature dependence of midinfrared peaks in high-Tc perovskites. PMID- 9980476 TI - Local probe of vortex pinning energies in the Bose glass. PMID- 9980477 TI - Staggered magnetic susceptibility in high-Tc systems: A scaling approach. PMID- 9980479 TI - Comment on "Impurity effects in d-wave superconductors" PMID- 9980478 TI - Layer-rigidity model and the mechanism for ion-diffusion-controlled kinetics in the bismuth cuprate 2212-to-2223 transformation. PMID- 9980480 TI - Erratum: Alternative approach to the dynamics of polarons in one dimension PMID- 9980481 TI - Exact results of a hard-core interacting system with a single impurity. PMID- 9980482 TI - Reversible propagating fingers in an antiferroelectric liquid crystal. PMID- 9980483 TI - Electronic transport in winding chains. PMID- 9980485 TI - Static properties of the S=1 one-dimensional antiferromagnet AgVP2S6. PMID- 9980484 TI - Relaxation and shear viscosity in mixed ionic melts. PMID- 9980487 TI - Crucial tests of spin filtering. PMID- 9980486 TI - Interpretation of x-ray-absorption dichroism experiments. PMID- 9980488 TI - Influence of an externally applied magnetic field on vectorial interaction in LiNbO3:Fe crystals. PMID- 9980489 TI - Exact finite-size spectrum for the multi-channel Kondo model and Kac-Moody fusion rules. PMID- 9980490 TI - Magnetically inhomogeneous ground state of CeAl3: An NMR study. PMID- 9980491 TI - Large crystalline-induced magnetic anisotropy and field-direction-dependent magnetoresistance in Co(11-bar00)/Cr(211) superlattices. PMID- 9980492 TI - Probing oscillatory exchange coupling with a paramagnet. PMID- 9980494 TI - Korteweg-de Vries equation in the vortex dynamics of an ultraclean type-II superconductor. PMID- 9980493 TI - High-pressure electron-spin dynamics in disordered conducting polymers. PMID- 9980495 TI - Anomalous magnetization in single-crystal kappa - PMID- 9980496 TI - Evidence for a strong spin-phonon interaction in cupric oxide. PMID- 9980497 TI - Anomalous phonon damping and thermal conductivity in insulating cuprates. PMID- 9980498 TI - Out-of-plane transverse resistivity in high-Tc superconductors as a signature of flow of rigid vortex lines. PMID- 9980499 TI - c-axis response of single- and double-layered cuprates. PMID- 9980500 TI - Neutron-diffraction study of the magnetic-field-induced metal-insulator transition in Pr0.7Ca0.3MnO3. PMID- 9980501 TI - Effect of pin density on planar vortex mobility. PMID- 9980502 TI - Permanent photoinduced changes in the transport properties of Bi2Sr2CaCu2O8+ delta thin films. PMID- 9980504 TI - Small-angle multiple neutron scattering in fractal media. PMID- 9980503 TI - Electric-field-dependent dielectric constant and nonlinear susceptibility in SrTiO3. PMID- 9980505 TI - Theoretical investigation of the high-pressure crystal structures of Ce and Th. PMID- 9980506 TI - Size-induced diffuse phase transition in the nanocrystalline ferroelectric PbTiO3. PMID- 9980507 TI - Mechanism of the incommensurate phase in lead oxide alpha -PbO. PMID- 9980508 TI - Neutron- and x-ray-scattering study of the two length scales in the critical fluctuations of SrTiO3. PMID- 9980509 TI - Phase-transition sequence of Rb2ZnCl4 obtained by study of internal vibrational modes. PMID- 9980510 TI - Cadmium and indium defects in ceria and their interaction with oxygen vacancies and small polarons. PMID- 9980511 TI - Test of the Peierls-Nabarro model for dislocations in silicon. PMID- 9980512 TI - Helium-atom-scattering study of multiphonon processes on LiF(001)<100> with temperature variation for specular and off-specular angles. PMID- 9980513 TI - Localized basis for effective lattice Hamiltonians: Lattice Wannier functions. PMID- 9980514 TI - High-pressure x-ray- and neutron-diffraction studies of BaF2: An example of a coordination number of 11 in AX2 compounds. PMID- 9980515 TI - Stability and the equation of state of alpha -manganese under ultrahigh pressure. PMID- 9980516 TI - Polarization-strain coupling in the mixed ferroelectric KTa1-xNbxO3. PMID- 9980517 TI - Stability of the hard-sphere icosahedral quasilattice. PMID- 9980519 TI - Simulations of liquid semiconductors using quantum forces. PMID- 9980518 TI - Mechanism of charge transport in discotic liquid crystals. PMID- 9980521 TI - Bismuth disproportionation in BaBiO3 studied by infrared and visible reflectance spectra. PMID- 9980520 TI - Low-temperature many-electron hopping conductivity in the Coulomb glass. PMID- 9980522 TI - Rotational dynamics of C604- and electronic excitation in Rb4C60. PMID- 9980523 TI - Dynamical instabilities in alpha -quartz and alpha -berlinite: A mechanism for amorphization. PMID- 9980524 TI - Characterization of the diffraction spectra of one-dimensional k-component Fibonacci structures. PMID- 9980525 TI - Interpretation of the band-structure results for elastic and acoustic waves by analogy with the LCAO approach. PMID- 9980527 TI - Statistical description of history-dependent creep constitutive equations for viscoelastic media. PMID- 9980526 TI - Applications of lattice-dynamic models to 67Zn Lamb-Mossbauer factors and second order Doppler shifts. PMID- 9980528 TI - Retarded modes of a lateral antiferromagnetic/nonmagnetic superlattice. PMID- 9980529 TI - Systematic analysis of the magnetic susceptibility in the itinerant electron model. PMID- 9980530 TI - Measurement of the spin-excitation continuum in one-dimensional KCuF3 using neutron scattering. PMID- 9980531 TI - Effects of coupling between chains on the magnetic excitation spectrum of KCuF3. PMID- 9980532 TI - Magnetic and electronic properties of gamma -Fe and gamma -Fe/Al particles in copper. PMID- 9980533 TI - First-principles calculations of electrical conductivity and giant magnetoresistance of Co||Cu||Co spin valves. PMID- 9980534 TI - Electronic theory for the nonlinear magneto-optical response of transition metals at surfaces and interfaces: Dependence of the Kerr rotation on the polarization and magnetic easy axis. PMID- 9980535 TI - Origin of orbital magnetization and magnetocrystalline anisotropy in TX ordered alloys (where T=Fe,Co and X=Pd,Pt). PMID- 9980536 TI - Pseudotemperature Monte Carlo study of a ground-state phase transition of the antiferromagnetic spin-S Ising model on a triangular lattice. PMID- 9980537 TI - Magnetic behavior of antiferromagnetically coupled layers connected by ferromagnetic pinholes. PMID- 9980538 TI - In-plane magnetization anisotropy in Gd2CuO4 single crystals. PMID- 9980539 TI - Magnetic anisotropies of sputtered Fe films on MgO substrates. PMID- 9980540 TI - Tunneling of a heavy particle with spin in a metal. PMID- 9980542 TI - Hole burning in a well-characterized noise field: Nonadherence to the Bloch equations. PMID- 9980541 TI - Effect of pressure on the Curie temperature of Fe3Pt. PMID- 9980544 TI - Renormalization-group study of interacting electrons. PMID- 9980543 TI - Monte Carlo simulation of the Heisenberg antiferromagnet on a triangular lattice: Topological excitations. PMID- 9980545 TI - Spin-dependent electron scattering in ferromagnetic Co layers on Cu(111). PMID- 9980546 TI - Phase diagram of magnetic multilayers: The role of biquadratic exchange. PMID- 9980547 TI - Angular dependence of coercivity in Nd-Fe-B sintered magnets: Proof that coherent rotation is not involved. PMID- 9980548 TI - Low-temperature specific heat of antiferromagnetic EuNi5P3 and mixed-valent EuNi2P2 in magnetic fields to 7 T. PMID- 9980549 TI - Frequency-dependent Cooper-pair tunneling in ultrasmall superconductor-insulator superconductor junctions. PMID- 9980550 TI - Vortex-pair production in superconducting films. PMID- 9980551 TI - Subharmonic structure of Shapiro steps in frustrated superconducting arrays. PMID- 9980552 TI - Euler Monte Carlo calculations for liquid 4He and 3He. PMID- 9980553 TI - Paramagnetic moment in field-cooled superconducting plates: Paramagnetic Meissner effect. PMID- 9980555 TI - Superconductivity and electrical properties in single-crystalline ultrathin Nb films grown by molecular-beam epitaxy. PMID- 9980554 TI - Influence of carrier injection on the metal-insulator transition in electron- and hole-doped R1-xAxNiO3 perovskites. PMID- 9980556 TI - Effect of impurity scattering on a (d+s)-wave superconductor. PMID- 9980557 TI - Magnetic scaling in cuprate superconductors. PMID- 9980558 TI - Electronic structure of the CuO3 chains in RBa2Cu3O6+x (R=Y or a rare earth). PMID- 9980559 TI - Universal behavior of susceptibility in the 110 K phase of the Bi-Pb-Sr-Ca-Cu-O system. PMID- 9980560 TI - Van Hove scenario for d-wave superconductivity in cuprates. PMID- 9980561 TI - Field-induced aging effects in inhomogeneous superconductors. PMID- 9980562 TI - Analysis and prediction of the critical current density across PMID- 9980563 TI - Point-contact characteristics of high-angle YBa2Cu3O7- delta step-edge junctions. PMID- 9980564 TI - Superconductivity in the two-dimensional Hubbard model. PMID- 9980565 TI - Micro-Raman study of isotope substitution in YBa2Cu318O6.2 during local laser annealing. PMID- 9980566 TI - Influence of Y2BaCuO5 particles on the microstructure of YBa2Cu3O7-x (123) Y2BaCuO5 (211) melt-textured superconductors. PMID- 9980567 TI - Doping and temperature dependence of c-axis optical phonons in YBa2Cu3Oy single crystals. PMID- 9980569 TI - Exact criterion for choosing the hopping operator in the four-slave-boson approach. PMID- 9980568 TI - Optical constants of lithium triborate crystals in the 55-71 eV region. PMID- 9980570 TI - Spectral weight transfer and mass renormalization in Mott-Hubbard systems SrVO3 and CaVO3: Influence of long-range Coulomb interaction. PMID- 9980571 TI - Band reconstructions of KxC60 caused by the cooperative Jahn-Teller effect. PMID- 9980572 TI - Canonical orbitals of the self-interaction-corrected local-spin-density approximation in doped systems. PMID- 9980573 TI - Exact diagonalization study of the two-dimensional t-J-Holstein model. PMID- 9980575 TI - Polaron-pair binding due to interchain coupling in conjugated polymers. PMID- 9980574 TI - Bandlike and localized states at extended defects in silicon. PMID- 9980576 TI - Electronic properties of (111) twin boundaries and twinning superlattices in lead sulfide. PMID- 9980578 TI - Laughlin wave function and one-dimensional free fermions. PMID- 9980577 TI - Suppression of deformation-potential electron-acoustic-phonon coupling in Si delta -doped GaAs structures. PMID- 9980580 TI - Experiments on inelastic scattering in the integer quantum Hall effect. PMID- 9980579 TI - Reconstruction-dependent orientation of Ag(111) films on Si(001). PMID- 9980581 TI - Metallic nature of the symmetric dimer model of Si(001)-(2 x 1). PMID- 9980583 TI - Self-oscillations of domains in doped GaAs-AlAs superlattices. PMID- 9980582 TI - Correlation effects in a quantum dot at high magnetic fields. PMID- 9980584 TI - Inelastic light scattering from a modulated two-dimensional electron gas in magnetic fields. PMID- 9980586 TI - Prediction of sawtooth oscillations in an electron Y-branch switch. PMID- 9980585 TI - Fractional periods of persistent currents in frustrated systems. PMID- 9980588 TI - Composite-fermion analysis of the double-layer fractional quantum Hall system. PMID- 9980587 TI - Hartree contribution to the band-gap renormalization in semiconductor microstructures. PMID- 9980589 TI - Electronic states of digital versus analog graded quantum wells. PMID- 9980591 TI - Effective-field approach to the Gaussian random-matrix model. PMID- 9980590 TI - Probing growth-related disorder by high-field transport in semiconductor superlattices. PMID- 9980592 TI - Thermovoltage across a vacuum barrier investigated by scanning tunneling microscopy: Imaging of standing electron waves. PMID- 9980594 TI - Step barrier for interlayer diffusion in Fe/Fe(100) epitaxial growth. PMID- 9980593 TI - Short-range magnetic order in FeN and NiN clusters. PMID- 9980595 TI - Possibility of a ferromagnetic Rh(001) surface: A plane-wave-basis partial-core pseudopotential approach. PMID- 9980596 TI - 3d and 4d x-ray-photoelectron spectra of Pr under gradual oxidation. PMID- 9980597 TI - Divalent scandium atoms in the cage of C84. PMID- 9980598 TI - Multiple-scattering calculations of the uranium L3-edge x-ray-absorption near edge structure. PMID- 9980599 TI - X-ray-absorption problem in metals within the one-electron approximation. PMID- 9980600 TI - Effect of charge transfer to the conduction band within a single-impurity model on the Ni 2p core-level line shapes of Ni compounds. PMID- 9980601 TI - Charge-density-wave phase slip and contact effects in NbSe3. PMID- 9980603 TI - Effect of electronic correlation on the shape of a large bipolaron: Four-lobed planar large bipolaron in an ionic medium. PMID- 9980602 TI - Electronic structure of PrNiO3 studied by photoemission and x-ray-absorption spectroscopy: Band gap and orbital ordering. PMID- 9980604 TI - Quadratic response theory of the energy loss of charged particles in an electron gas. PMID- 9980605 TI - Spectral correlations from the metal to the mobility edge. PMID- 9980606 TI - Asymmetric Hubbard chain at half-filling. PMID- 9980608 TI - Anderson-Mott transition as a quantum-glass problem. PMID- 9980607 TI - Magnetoresistance of multiply connected Al samples. PMID- 9980610 TI - Hydrogen diffusion in a-Si:H: Solution of the tracer equations including capture by exchange. PMID- 9980609 TI - Nonlinear transport in photoexcited plasma in semiconductors: Non-Ohmic mobility and a generalized Einstein relation. PMID- 9980611 TI - Calculation of the line shape of one-phonon replicas in polar semiconductors having direct forbidden band gaps. PMID- 9980612 TI - Characterization of a strain-inducing defect in CdTe by magnetoluminescence spectroscopy. PMID- 9980613 TI - d-band excitations in II-VI semiconductors: A broken-symmetry approach to the core hole. PMID- 9980614 TI - High-resolution study of the magnetic-field effect on the 4E state of Mn2+ in cubic ZnS by laser spectroscopy. PMID- 9980615 TI - Effects of ordering on the electron effective mass and strain deformation potential in GaInP2: Deficiencies of the k PMID- 9980616 TI - Atomic motions in an unusual molecular semiconductor: NaSn. PMID- 9980617 TI - Theory of femtosecond photon-echo decay in semiconductors. PMID- 9980618 TI - Preparation of a-GeOx:H alloys: Vibrational, optical, and structural properties. PMID- 9980619 TI - In-plane dispersion relations of InAs/AlSb/GaSb/AlSb/InAs interband resonant tunneling diodes. PMID- 9980620 TI - Surface crystal field at the Er/Si(111) interface studied by soft-x-ray linear dichroism. PMID- 9980621 TI - Quasiepitaxial growth of the organic molecular semiconductor 3,4,9,10 perylenetetracarboxylic dianhydride. PMID- 9980622 TI - Scattering interference of energetic electrons along atomic chains: The effect of the atomic environment. PMID- 9980623 TI - Radiative states in type-II GaSb/GaAs quantum wells. PMID- 9980624 TI - Edge states, Aharonov-Bohm oscillations, and thermodynamic and spectral properties in a two-dimensional electron gas with an antidot. PMID- 9980625 TI - Optical properties of twinning superlattices in diamond-type and zinc-blende-type semiconductors. PMID- 9980626 TI - Surface modification of GaAs(110) by low-energy ion irradiation. PMID- 9980627 TI - Hofstadter spectra in two-dimensional superlattice potentials with arbitrary modulation strength. PMID- 9980628 TI - Landau levels in the presence of dilute short-range scatterers. PMID- 9980630 TI - Relative importance of self-consistency and variable symmetry in the calculation of exciton energies in type-I and type-II semiconductor heterostructures. PMID- 9980629 TI - Structural and electronic evolution on the Ge(111)-Ag surface. PMID- 9980631 TI - Valence band structure, edge states, and interband absorption in quantum-well wires in high magnetic fields. PMID- 9980632 TI - Many-body analysis of the effects of electron density and temperature on the intersubband transition in GaAs/AlxGa1-xAs multiple quantum wells. PMID- 9980633 TI - Theoretical study on interband tunneling of holes through GaAs/AlAs/GaAs single barrier heterostructures. PMID- 9980634 TI - Universal equilibrium currents in the quantum Hall fluid. PMID- 9980636 TI - Molecular-orbital study of Li and LiOH adsorbed on a Cu(001) surface. PMID- 9980635 TI - Optical-phonon emission in GaAs/AlAs multiple-quantum-well structures determined by hot-electron luminescence. PMID- 9980637 TI - Bi-intercalation of ICl into a stage-5 FeCl3 graphite intercalation compound. PMID- 9980638 TI - Effects of surface roughness on the electronic shell structure of metal clusters. PMID- 9980639 TI - Chemical shifts and coupling interactions for the bonding vibrational modes for CO/Cu(111) and (100) surfaces. PMID- 9980640 TI - Scattering of He atoms from KCN(001): Analysis of the energy exchange. PMID- 9980642 TI - Modified tight-binding equations for wave functions of semi-infinite crystals and interfaces. PMID- 9980641 TI - Determination of fractal dimension by cyclic I-V studies: The Laplace-transform method. PMID- 9980643 TI - Electron-electron and electron-phonon interactions in alkali-metal-doped C60. PMID- 9980644 TI - Influence of a polarizable medium on the nonlocal optical response of a metal surface. PMID- 9980645 TI - Surface states and photoemission of magnetic multilayer systems. PMID- 9980646 TI - Crack stability and branching at interfaces. PMID- 9980647 TI - Theory of the excitonic effect in solid C60. PMID- 9980648 TI - Coarsening and slope evolution during unstable spitaxial growth. PMID- 9980649 TI - Erratum: Low-frequency Raman scattering from small silver particles embedded in SiO2 thin films PMID- 9980650 TI - High-resolution electron microscopy of discommensuration in the nearly commensurate phase on warming of 1T-TaS2. PMID- 9980651 TI - Phase-transition behavior of the spontaneous polarization and susceptibility of ferroelectric thin films. PMID- 9980653 TI - Transmission electron microscopy study of high-Zr-content lead zirconate titanate. PMID- 9980652 TI - Measurement of the linear polarization of channeling radiation in silicon and diamond. PMID- 9980654 TI - Nonempirical calculation of the Pb(Sc0.5Ta0.5)O3-PbTiO3 quasibinary phase diagram. PMID- 9980655 TI - Stable and x-ray induced commensurate and incommensurate phases in betaine calcium chloride dihydrate. PMID- 9980656 TI - Disorder-driven pretransitional tweed pattern in martensitic transformations. PMID- 9980657 TI - Damage-depth profiling of an ion-irradiated polymer by monoenergetic positron beams. PMID- 9980658 TI - Ab initio calculations of structures, and Raman and infrared spectra of vitreous B2O3. PMID- 9980659 TI - 87Rb NMR of the structural phase transition in RbSCN. PMID- 9980660 TI - Ion-beam modification of fullerene. PMID- 9980662 TI - Nuclear superfluorescence: A feasibility study based on the generalized Haake Reibold theory. PMID- 9980661 TI - Ion implantation in tetrahedral amorphous carbon. PMID- 9980663 TI - Photorefractive effect in Cd13P4S22I2. PMID- 9980665 TI - Calculations of positron lifetimes in a jog and vacancies on an edge-dislocation line in Fe. PMID- 9980664 TI - Near-edge optical absorption in liquid iodine under high pressure. PMID- 9980666 TI - Magnetic and calorimetric study of a single grain of quasicrystalline Al-Pd-Mn. PMID- 9980668 TI - Effective parameters of a statistically homogeneous fluid with strong density and compressibility fluctuations. PMID- 9980667 TI - Atomic-structure model of i-(Al0.570Cu0.108Li0.322). PMID- 9980670 TI - Explanation for the sqrt E -dependent mobilities of charge transport in molecularly doped polymers. PMID- 9980669 TI - Electrophysical properties of metal-solid-electrolyte composites. PMID- 9980671 TI - Nanoscale-crystallite nucleation and growth in amorphous solids. PMID- 9980672 TI - Static, dynamic, and electronic properties of liquid gallium studied by first principles simulation. PMID- 9980673 TI - Brillouin and Raman cross sections in silicate glasses. PMID- 9980675 TI - Subpicosecond time-resolved Raman investigation of optical phonon modes in Cr doped forsterite. PMID- 9980674 TI - Phonon distribution in a model polariton system. PMID- 9980676 TI - Mobius inversion transform for diamond-type materials and phonon dispersions. PMID- 9980678 TI - Dynamical renormalization of anharmonic lattices at the onset of fracture: Analytical results for scaling, noise, and memory. PMID- 9980677 TI - Tracer-diffusion study of Cu+ diffusion in CuBr. PMID- 9980680 TI - Effect of spin-phonon interaction on the Raman spectra of quasi-two-dimensional Heisenberg antiferromagnets. PMID- 9980679 TI - Fluctuation subharmonic and multiharmonic phonon transmission and Kapitza conductance between crystals with very different vibrational spectra. PMID- 9980682 TI - Aging in spin glasses as a random walk: Effect of a magnetic field. PMID- 9980681 TI - Mode assignment for magnetic excitations associated with Co2+ impurities in antiferromagnetic FeF2. PMID- 9980683 TI - Bosonic mean-field theory for frustrated Heisenberg antiferromagnets in two dimensions. PMID- 9980684 TI - Nuclear-quadrupole double-resonance study of the solid solution Rb1-xTlxH2PO4. PMID- 9980685 TI - Magnetic reorientation transition of Gd(0001)/W(110) films. PMID- 9980686 TI - Polar magneto-optics in simple ultrathin-magnetic-film structures. PMID- 9980688 TI - Spin-glass-like behavior of the incommensurate composite phase LaCrS3. PMID- 9980687 TI - Polarization and interlayer coupling in Co-Nb/Pd multilayers. PMID- 9980689 TI - Hyperfine magnetic field in mechanically alloyed Fe-Cu. PMID- 9980691 TI - Block spins and chirality in the frustrated Heisenberg model on kagome-acute and triangular lattices. PMID- 9980690 TI - Giant magnetoresistance in Fe/Ag multilayers and its anomalous temperature dependence. PMID- 9980692 TI - Line of continuously varying criticality in the Ashkin-Teller quantum chain. PMID- 9980693 TI - Electron paramagnetic resonance versus spin-dependent recombination: Excited triplet states of structural defects in irradiated silicon. PMID- 9980694 TI - Effects of Fermi-surface topology on the electronic properties of the two dimensional t-t' model. PMID- 9980695 TI - Proximity-induced superconductivity in a narrow metallic wire. PMID- 9980696 TI - Registered state and a two-dimensional Bose liquid of 4He in mesopores of hectorite. PMID- 9980697 TI - Vortex-lattice melting in superconducting fullerene Rb3C60. PMID- 9980699 TI - Vortices in stratified and nonlocal superconductors. PMID- 9980698 TI - Magnetic transitions and nearly reentrant superconducting properties of HoNi2B2C. PMID- 9980700 TI - Structural and dynamical properties of superfluid helium: A density-functional approach. PMID- 9980701 TI - Nucleation in supersaturated solutions of 3He in 4He at negative pressures. PMID- 9980702 TI - Complete inversion of the Meissner effect in Bi2Sr2CaCu2O8+ delta ceramics at ultralow fields. PMID- 9980703 TI - Generalized Gorkov's equation for nonequilibrium superconductivity. PMID- 9980704 TI - Bounds for the phonon-roton dispersion in superfluid 4He. PMID- 9980705 TI - Elastic theory of flux lattices in the presence of weak disorder. PMID- 9980706 TI - Properties of odd-gap superconductors. PMID- 9980707 TI - Impurity effects on the anisotropic s-wave superconductor of the interlayer pair tunneling mechanism. PMID- 9980708 TI - Participation-ratio entropy and critical fluctuations in the thermodynamics of pancake vortices. PMID- 9980709 TI - Electron-spin-lattice relaxation in GdBa2Cu3O6+x. PMID- 9980710 TI - Physical quantities in nearly antiferromagnetic and superconducting states of the two-dimensional Hubbard model and comparison with cuprate superconductors. PMID- 9980711 TI - Transport critical current in c-axis-oriented Bi1.8Pb0.4Sr2Ca2Cu3Oy/Ag tapes. PMID- 9980712 TI - Quantum tunneling of flux lines in a high-Tc superconductor. PMID- 9980713 TI - Low-field ac-susceptibility study of flux creep in metal-substituted ErBa2Cu3O7- delta. PMID- 9980715 TI - Role of elasticity associated with oxygen ordering in YBa2Cu3Oz. PMID- 9980714 TI - Magnetic relaxation and quantum tunneling of vortices in a polycrystalline Hg0.8Tl0.2Ba2Ca2Cu3O8+ delta superconductor. PMID- 9980716 TI - Structural aspects of pressure-dependent hole ordering in La1.67M0.33NiO4 (M=Ca, Sr, or Ba). PMID- 9980717 TI - Manifestation of a clear gap structure from point-contact and tunneling spectroscopy of YBa2Cu3O7-x and YbBa2Cu3O7-x single crystals. PMID- 9980718 TI - Relationship of Sr2RuO4 to the superconducting layered cuprates. PMID- 9980720 TI - Negative-U extended Hubbard model for doped barium bismuthates. PMID- 9980719 TI - Structural stability of LuBa2Cu3O7- delta and superconductivity in thin films of Lu1-xMxBa2Cu3O7- delta (M=Pr, Tb, and Ce). PMID- 9980721 TI - Synthesis and characterization of compounds Sr2RMCu2O8- delta (R=Pr, Nd, Sm, Eu, Gd; M=Nb, Ta). PMID- 9980722 TI - Comment on "Optical absorption measurements of hydrogen at megabar pressures" PMID- 9980723 TI - Reply to "Comment on 'Optical absorption measurements of hydrogen at megabar pressures' " PMID- 9980724 TI - Comment on "Multiple-histogram Monte Carlo study of the Ising antiferromagnet on a stacked triangular lattice" PMID- 9980725 TI - Reply to "Comment on 'Multiple-histogram Monte Carlo study of the Ising antiferromagnet on a stacked triangular lattice' " PMID- 9980726 TI - Lifshitz-Slyozov scaling for late-stage coarsening with an order-parameter dependent mobility. PMID- 9980727 TI - Detection of paramagnetic centers on amorphous-SiO2 grain surfaces using positronium. PMID- 9980728 TI - Generalization of the Schwartz-Soffer inequality for correlated random fields. PMID- 9980729 TI - Indirect exchange coupling for orthogonal anisotropies. PMID- 9980731 TI - Incommensurate lattice modulation in the spin-Peierls system CuGeO3. PMID- 9980730 TI - Spin-density-wave transition and resistivity minimum of the Bechgaard salt (TMTSF)2NO3 at high magnetic field, where TMTSF is tetramethyltetraselenafulvalene. PMID- 9980732 TI - Magnetic excitations in a highly frustrated pyrochlore antiferromagnet. PMID- 9980734 TI - Propagating S=1/2 particles in S=1 Haldane-gap systems. PMID- 9980733 TI - Reversed time in Mossbauer time spectra. PMID- 9980735 TI - Numerical renormalization-group study of the correlation functions of the antiferromagnetic spin-1/2 Heisenberg chain. PMID- 9980736 TI - Pressure-induced polymerization of ternary fulleride superconductors. PMID- 9980737 TI - Clear distinction between the underdoped and overdoped regime in the Tc suppression of Cu-site-substituted high-Tc cuprates. PMID- 9980739 TI - Thermal conductivity and structural instability in La- and Cu-site-substituted La2CuO4. PMID- 9980738 TI - Observation of below-gap plasmon excitations in superconducting YBa2Cu3O7 films. PMID- 9980740 TI - Magnetotransport behavior of polycrystalline YBa2Cu3O7: A possible role for surface barriers. PMID- 9980741 TI - Phonon-drag thermopower correlations to Tc in superconducting SrxNd1-xCuO2- delta : Evidence for phonon-mediated pairing in the high-Tc parent compounds. PMID- 9980743 TI - Negative magnetoresistance in the c-axis resistivity of Bi2Sr2CaCu2O8+ delta and YBa2Cu3O6+x. PMID- 9980742 TI - Critical scaling of the transport behavior and the magnetic phase diagram of polycrystalline YBa2Cu3O7. PMID- 9980744 TI - Anomalous magnetization in single-crystal Tl2Ba2CuO6: Evidence of dimensional crossover. PMID- 9980746 TI - Light scattering from gap excitations and bound states in SmB6. PMID- 9980745 TI - Influence of charge and magnetic ordering on the insulator-metal transition in Pr1-xCaxMnO3. PMID- 9980747 TI - Barrier between localized and shallow neutral donor states in GaAs:Ge. PMID- 9980749 TI - Hydrogen interactions with self-interstitials in silicon. PMID- 9980748 TI - Ab initio electronic-structure calculations for II-VI semiconductors using self interaction-corrected pseudopotentials. PMID- 9980751 TI - Enhanced optical properties in porous silicon microcavities. PMID- 9980750 TI - Holographic time-of-flight measurements of the hole-drift mobility in a photorefractive polymer. PMID- 9980752 TI - Spin splitting of conduction subbands in GaAs-Ga0.7Al0.3As heterostructures. PMID- 9980753 TI - Lead-induced transition to chaos in ballistic mesoscopic billiards. PMID- 9980754 TI - Observation of Wannier-Stark ladder transitions in InxGa1-xAs-GaAs piezoelectric superlattices. PMID- 9980755 TI - Subpicosecond hole tunneling by nonresonant delocalization in asymmetric double quantum wells. PMID- 9980756 TI - Path-dependent conductivity in the regime of floating delocalized states. PMID- 9980757 TI - Metal-semiconductor fluctuation in the Sn adatoms in the Si(111)-Sn and Ge(111) Sn ( sqrt 3 x sqrt 3)R30 degrees reconstructions. PMID- 9980759 TI - Aharonov-Bohm oscillations in a mesoscopic ring with a quantum dot. PMID- 9980758 TI - Symmetry and electronic structure of the Mn impurity in ZnS nanocrystals. PMID- 9980761 TI - Transport through dirty Luttinger liquids connected to reservoirs. PMID- 9980760 TI - Resonance fluorescence and polariton effects in GaAs thin layers. PMID- 9980762 TI - Observation of the nu =1 quantum Hall effect in a strongly localized two dimensional system. PMID- 9980763 TI - Far-infrared response of holes in quantum dots: Band structure effects and the generalized Kohn's theorem. PMID- 9980764 TI - Effect of strain on surface diffusion and nucleation. PMID- 9980765 TI - Promotion of catalytic reactions by depopulation of surface states. PMID- 9980766 TI - Atomic- and electronic-structure study on the layers of 4Hb-TaS2 prepared by a layer-by-layer etching technique. PMID- 9980767 TI - Superstructures and defect structures revealed by atomic-scale STM imaging of WO3(001). PMID- 9980768 TI - Predictions for neutron scattering and photoemission experiments on CuGeO3. PMID- 9980769 TI - Submonolayers of adsorbates on stepped Co/Cu(100): Switching of the easy axis. PMID- 9980770 TI - Mechanisms of initial alloy formation for Pd on Cu(100) studied by STM. PMID- 9980771 TI - Localized orbital theory of electronic structure: A simple application. PMID- 9980773 TI - Photoemission and bremsstrahlung isochromat spectra of U3P4 and U3As4. PMID- 9980772 TI - Impurity effects on atomic bonding in Ni3Al. PMID- 9980774 TI - X-ray-edge singularities with nonconstant density of states: A renormalization group approach. PMID- 9980776 TI - Fine structure and fractional M/N Aharonov-Bohm effect. PMID- 9980775 TI - Resonance Raman enhancement for photoinduced polaronic states of a quasi-one dimensional mixed-valence platinum complex. PMID- 9980777 TI - Pressure effects on the electronic structure and low-temperature states in the alpha -(BEDT-TTF)2MHg(SCN)4 organic-conductor family (M=K, Rb, Tl, NH4). PMID- 9980779 TI - Conjugate-gradient methods for metallic systems and band-structure calculations. PMID- 9980778 TI - Symmetry-selective resonant inelastic x-ray scattering of C60. PMID- 9980780 TI - Effects of geometric Berry phase on persistent currents in large-U one dimensional Hubbard rings. PMID- 9980781 TI - Mixed boson-fermion description of correlated electrons: Fluctuation corrections in the symmetric treatment. PMID- 9980782 TI - Chemical pressure and charge-density waves in rare-earth tritellurides. PMID- 9980783 TI - Dielectric function and optical conductivity of TiOx (0.8X transition in GaAs/AlGaAs quantum films, wires, and dots. PMID- 9980799 TI - Effect of impurities on the current magnification in mesoscopic open rings. PMID- 9980801 TI - Persistent-photoconductivity effect in delta -doped Al0.48In0.52As/Ga0.47In0.53As heterostructures. PMID- 9980802 TI - Stability and electronic properties of nanoscale silicon clusters. PMID- 9980803 TI - Measurement of the In0.52Al0.48As valence-band hydrostatic deformation potential and the hydrostatic-pressure dependence of the In0.52Al0.48As/InP valence-band offset. PMID- 9980804 TI - Optically detected cyclotron-resonance studies of radiative processes in AlxGa1 xAs/GaAs high-electron-mobility structures. PMID- 9980805 TI - Experimental determination of the conduction-band offset at GaAs/Ga1-xAlxAs heterojunctions with the use of ballistic electrons. PMID- 9980806 TI - Edge-state transport in finite antidot lattices. PMID- 9980807 TI - Fourfold anisotropy and structural behavior of epitaxial hcp Co/GaAs(001) thin films. PMID- 9980808 TI - Surface phonons of the Si(111)-7 x 7 reconstructed surface. PMID- 9980809 TI - Phenomenological electrodynamics of electronic superlattices. PMID- 9980810 TI - Coupling of geometric confinement and magnetic confinement in In0.09Ga0.91As/GaAs quantum wells in magnetic fields with varying orientations. PMID- 9980812 TI - Theoretical study of Ti adsorption on Si(001) surfaces. PMID- 9980811 TI - Thermal carrier emission from a semiconductor quantum well. PMID- 9980813 TI - Effect of magnetic modulation on Bloch electrons on a two-dimensional square lattice. PMID- 9980814 TI - Linear-response theory of Coulomb drag in coupled electron systems. PMID- 9980815 TI - Magnetoplasmon emission versus Landau-level scattering in resonant tunneling through double-barrier structures. PMID- 9980816 TI - Electron relaxation in the quantum-Hall-effect geometry: One- and two-phonon processes. PMID- 9980817 TI - Two-photon photoelectron spectroscopy of GaP(110) after sputtering, annealing, and multishot laser damage. PMID- 9980819 TI - Enhanced charge and spin currents in the one-dimensional disordered mesoscopic Hubbard ring. PMID- 9980818 TI - Plasmon enhancement of Coulomb drag in double-quantum-well systems. PMID- 9980820 TI - Charge transfer at double-layer to single-layer transition in double-quantum-well systems. PMID- 9980821 TI - Lifetime of two-dimensional electrons measured by tunneling spectroscopy. PMID- 9980822 TI - Aharonov-Bohm effect induced by mutual inductance for an array of mesoscopic rings. PMID- 9980823 TI - Photon-assisted transport through quantized energy states in a lateral dual-gate device. PMID- 9980824 TI - Raman spectroscopy of C60 solid films. PMID- 9980825 TI - Theory of carbon nanotube growth. PMID- 9980826 TI - Necessity of self-energy corrections in LEED theory for Xe(111): Comparison between theoretical and experimental spin-polarized LEED data. PMID- 9980827 TI - Growth of conjugated oligomer thin films studied by atomic-force microscopy. PMID- 9980828 TI - Statistical error analysis of surface-structure parameters determined by low energy electron and positron diffraction: Data errors. PMID- 9980829 TI - Determination of the surface atomic geometry of PbTe(100) by dynamical low-energy electron-diffraction intensity analysis. PMID- 9980830 TI - Evidence for crystal-field splitting in surface-atom photoemission from potassium. PMID- 9980831 TI - Scaling and dynamics of low-frequency hysteresis loops in ultrathin Co films on a Cu(001) surface. PMID- 9980832 TI - Initial stages of the growth of SrF2 on InP. PMID- 9980833 TI - Circular dichroism in the angular distribution of core photoelectrons from Si(001): A photoelectron-diffraction analysis. PMID- 9980834 TI - Static conductivity and superconductivity of carbon nanotubes: Relations between tubes and sheets. PMID- 9980835 TI - Terrace distribution during sputtering and recovery of InSb(110) studied by He atom scattering. PMID- 9980836 TI - Surface plasmon dispersion and damping on Ag(111). PMID- 9980837 TI - Electronic structure, total energies, and STM images of clean and oxygen-covered Al(111). PMID- 9980838 TI - Structure, stability, and vibrational properties of polymerized C60. PMID- 9980839 TI - Ab initio calculation of phonon spectra for graphite, BN, and BC2N sheets. PMID- 9980840 TI - Low-load friction behavior of epitaxial C60 monolayers under Hertzian contact. PMID- 9980842 TI - Up-converted luminescence by two- and three-photon excitation in LaF3:Nd3+ crystals. PMID- 9980841 TI - Luminescence spectra of uranyl ions adsorbed on disperse SiO2 surfaces. PMID- 9980843 TI - Off-center sites in some lightly intercalated alkali-metal fullerides. PMID- 9980845 TI - Phonons of the cis-polyacetylene chain. PMID- 9980844 TI - Theoretical stability limit of diamond at ultrahigh pressure. PMID- 9980846 TI - Spin stiffness of frustrated Heisenberg antiferromagnets: Finite-size scaling. PMID- 9980847 TI - Pressure effects on the magnetoresistance in doped manganese perovskites. PMID- 9980848 TI - Exactly solvable multichain supersymmetric t-J model. PMID- 9980849 TI - Observation of photoinduced bulk current in metals. PMID- 9980850 TI - Ferromagnetic resonance and magnetic homogeneity in a giant-magnetoresistance material La2/3Ba1/3MnO3. PMID- 9980851 TI - Electron spin resonance of Er3+ in YBiPt. PMID- 9980852 TI - Gap-formation mechanism of the Kondo-necklace model. PMID- 9980853 TI - Magnetic coupling in 3d transition-metal monolayers and bilayers on bcc (100) iron. PMID- 9980854 TI - Charge fluctuations on a superconducting island. PMID- 9980855 TI - Raman modes of the apical oxygen in mercury-based superconductors. PMID- 9980857 TI - Normal-state transport and magnetic properties of RNi2B2C (R=Y, Ho, La). PMID- 9980856 TI - Soft-x-ray-emission studies of YNi2B2C and LaNi2B2C: Observation of the B 2p and C 2p partial density of states. PMID- 9980859 TI - Odd parity and line nodes in heavy-fermion superconductors. PMID- 9980858 TI - Statistical interparticle potential between two anyons. PMID- 9980860 TI - Quasiparticle-pair interference effect in proximity-coupled junction ladders. PMID- 9980862 TI - Theory of superexchange in CuO2. PMID- 9980861 TI - Magnetic-field effect on the specific heat of PrBa2(Cu1-xGax)3O7- delta. PMID- 9980863 TI - Polarization selection rules and superconducting gap anisotropy in Bi2Sr2CaCu2O8. PMID- 9980864 TI - Metal-antiferromagnetic insulator transition in the charge-transfer model. PMID- 9980865 TI - Theoretical study on Cl L23 NEXAFS and UV absorption data for metal chlorides. PMID- 9980867 TI - X-ray-absorption spectroscopy and n-body distribution functions in condensed matter. II. Data analysis and applications. PMID- 9980866 TI - X-ray-absorption spectroscopy and n-body distribution functions in condensed matter. I. Theory. PMID- 9980868 TI - Atomistic simulation of thermomechanical properties of beta -SiC. PMID- 9980869 TI - E-symmetry phonon polaritons in PbTiO3. PMID- 9980870 TI - First-principles study of solid Ar and Kr under high compression. PMID- 9980871 TI - Range profiles in self-ion-implanted crystalline Si. PMID- 9980872 TI - Electronic structure and phase stability study in the Ni-Ti system. PMID- 9980873 TI - Ab initio atomistic simulation of the strength of defective aluminum and tests of empirical force models. PMID- 9980874 TI - Site-selective laser-spectroscopy studies of the intrinsic 1.9-eV luminescence center in glassy SiO2. PMID- 9980875 TI - 14N NMR study of the glass transition in (NH4I)0.44(KI)0.56. PMID- 9980876 TI - Thermodynamics and vibrational excitations of a two-dimensional nanoscale model material. PMID- 9980877 TI - Dielectric relaxation of liquids at the surface of a porous glass. PMID- 9980878 TI - Features of a eutectoid reaction in a Ti-40 at. % Al alloy: Evidence for an amorphous-state formation from a crystal. PMID- 9980879 TI - Effective-medium theories for spheroidal particles randomly oriented on a plane: Application to the optical properties of a SiC whisker-Al2O3 composite. PMID- 9980880 TI - Anharmonic effects and second-neighbor interactions of local modes in Cr4+-doped forsterite probed by higher-order resonance Raman scattering. PMID- 9980881 TI - Long-range electron-phonon correlation and Peierls dimerization in the one dimensional molecular-crystal model. PMID- 9980883 TI - Microscopic theory of orientational disorder and lattice instability in solid C70. PMID- 9980882 TI - Quasisoliton states in a two-dimensional discrete model. PMID- 9980884 TI - Exciton solitons in molecular crystals. PMID- 9980886 TI - Ground state of a triangular quantum antiferromagnet: Fixed-node Green-function Monte Carlo study. PMID- 9980885 TI - Ultrasonic study of magnetoelastic effects in the spin-Peierls state of CuGeO3. PMID- 9980887 TI - Magnetostatic modes in Fibonacci magnetic and nonmagnetic multilayers. PMID- 9980888 TI - Semiclassical description of spin ladders. PMID- 9980889 TI - Low-temperature susceptibilities of the quasi-one-dimensional spin-1/2 Heisenberg antiferromagnets (6MAP)CuCl3 and (3MAP)CuCl3: Spin-Peierls transition versus broken-chain effects. PMID- 9980890 TI - Room-temperature magnetic phases of Fe on fcc Co(001) and Ni(001). PMID- 9980891 TI - Surface magnetism studied within the mean-field approximation of the Hubbard model. PMID- 9980892 TI - Spin polarization and magnetic dichroism in photoemission from core and valence states in localized magnetic systems. IV. Core-hole polarization in resonant photoemission. PMID- 9980894 TI - Electronic states induced by interface doping of Cu/Ni(100) with Co. PMID- 9980893 TI - Pressure effects on the dimerization in the spin-Peierls state of CuGeO3. PMID- 9980895 TI - Local magnetic properties of antiferromagnetic FeBr2. PMID- 9980896 TI - Evidence of spin-density-wave to spin-glass transformation in YNd Alloys. PMID- 9980897 TI - Magnetic structure of monolayer-range Cr films deposited on Fe(001). PMID- 9980898 TI - Magnetic properties and giant magnetoresistance of melt-spun granular Cu100-x-Cox alloys. PMID- 9980899 TI - Characterization of the structural and magnetic fluctuations near the spin Peierls transition in CuGeO3. PMID- 9980900 TI - Large length-scale fluctuations at the spin-Peierls transition in CuGeO3. PMID- 9980901 TI - Current-perpendicular and current-parallel giant magnetoresistances in Co/Ag multilayers. PMID- 9980902 TI - Electric field in superconductors with rectangular cross section. PMID- 9980903 TI - Effect of disorder on synchronization in prototype two-dimensional Josephson arrays. PMID- 9980904 TI - Model for low-field microwave absorption in granular type-II superconductors. PMID- 9980905 TI - Phonon-induced electron-electron interaction in disordered superconductors. PMID- 9980907 TI - Conductance anomalies for normal-metal-insulator-superconductor contacts. PMID- 9980906 TI - Optical properties of single-crystal La2CuO4+ delta. PMID- 9980909 TI - Magnetic properties of superconducting K3C60 and Rb3C60 synthesized from large single-crystal fullerenes. PMID- 9980908 TI - Nonlinear transport of electrons in a quasi-one-dimensional channel on the liquid helium surface. PMID- 9980910 TI - Electron correlation in the kappa -phase family of BEDT-TTF compounds studied by 13C NMR, where BEDT-TTF is bis(ethylenedithio)tetrathiafulvalene. PMID- 9980911 TI - Superconductivity at 8 K in samarium-doped C60. PMID- 9980912 TI - Chern-Simons superconductivity at finite magnetic field. PMID- 9980913 TI - Transport properties and vortex-glass melting in TlnBa2Ca2Cu3Ox (n=1,2) films: Correlation of scaling exponents with crystal anisotropy. PMID- 9980914 TI - Crystal structure of HgBa2Ca2Cu3O8+ delta at high pressure (to 8.5 GPa) determined by powder neutron diffraction. PMID- 9980916 TI - Low-temperature superstructures and incommensurate phases of YBa2Cu3O6+x. PMID- 9980915 TI - Raman study of intermultiplet crystal-field excitations in Nd2CuO4. PMID- 9980917 TI - Pinning mechanisms in YBa2Cu3O7- delta single crystals. PMID- 9980919 TI - Optical properties of YBa2Cu3O7- delta thin films. PMID- 9980918 TI - Oxygen ordering and phase separation in La2CuO4+ delta. PMID- 9980920 TI - Defect mechanism of photoinduced superconductivity in YBa2Cu3O6+x. PMID- 9980921 TI - Changes of the dimensionality and Tc through the iodine intercalation and oxidation in Bi2Sr2CaCu2O8+ delta single crystals. PMID- 9980922 TI - Influence of next-nearest-neighbor electron hopping on the static and dynamical properties of the two-dimensional Hubbard model. PMID- 9980923 TI - Excitation spectra of the negative-U Hubbard model: A small-cluster study. PMID- 9980924 TI - Discontinuity lines in rectangular superconductors with intrinsic and extrinsic anisotropies. PMID- 9980925 TI - First-principles calculation of the transition temperature Tc for HgBa2CuO4+ delta high-temperature superconductors via dipolon theory. PMID- 9980926 TI - Chromium clustering and ordering in Hg1-xCrxSr2CuO4+ delta. PMID- 9980927 TI - Magnetoresistance of PrBa2Cu3O7- delta thin films. PMID- 9980928 TI - Erratum: Analysis of cubic zero-field splitting of Fe3+ and Mn2+ in tetrahedral coordination PMID- 9980929 TI - Erratum: Interactions for odd- omega gap singlet superconductors PMID- 9980930 TI - Erratum: Observation of an electromagnetic absorption peak in the millimeter wave range in liquid helium at the superfluid lambda transition PMID- 9980931 TI - Destruction of Peierls dimerization in the molecular-crystal model: Effects of quantum phonon fluctuations. PMID- 9980932 TI - Identification of local spin fluctuations by weak localization. PMID- 9980934 TI - Spin-wave excitation spectra and spectral weights in square lattice antiferromagnets. PMID- 9980933 TI - Magnetic coupling at the Mn/Fe(001) interface. PMID- 9980935 TI - Anomalous hydrostatic pressure dependence of the Curie temperature of the Kondo lattice compound YbNiSn to 38 GPa. PMID- 9980936 TI - Spin-resolved Fe L3M45M45 Auger transition on and off resonance: The effect of exchange correlation. PMID- 9980937 TI - Low-temperature order in the heavy-fermion compound CeCu6. PMID- 9980938 TI - Dynamical properties of the single-hole t-J model on a 32-site square lattice. PMID- 9980939 TI - Shubnikov-de Haas oscillations in the organic superconductor kappa -(BEDT-TTF)2Cu PMID- 9980940 TI - Numerical simulation of vortex arrays in thin superconducting films. PMID- 9980941 TI - Ground-state properties of the one-dimensional Kondo lattice at partial band filling. PMID- 9980942 TI - Evidence for chain superconductivity in near-stoichiometric YBa2Cu3Ox single crystals. PMID- 9980943 TI - Anisotropy of the penetration depth in YBa2Cu3O7- delta : Josephson-tunneling studies. PMID- 9980944 TI - Interplane coupling in the superconductor Y2Ba4Cu7O15 as revealed by NQR spin echo double resonance. PMID- 9980945 TI - Parity of the order parameter in high-temperature superconductors with respect to a pi /2 rotation. PMID- 9980946 TI - Antiferromagnetic excitations and van Hove singularities in YBa2Cu3O6+x. PMID- 9980947 TI - XAFS measurements of negatively correlated atomic displacements in HgBa2CuO4+ delta. PMID- 9980948 TI - Hall anomaly in the vortex state of La2-xSrxCuO4. PMID- 9980949 TI - Boson mediators of high-Tc superconductivity: Phonons versus composite bosons from the superconducting phenomenology. PMID- 9980950 TI - Intensity of the B1g phonon Raman scattering in YBa2Cu3O7: Comparison of normal and superconducting states. PMID- 9980951 TI - High-pressure fluorescence line narrowing of Eu(III)-doped sodium disilicate glass. PMID- 9980952 TI - Evidence for diffusion-limited kinetics of ion-beam-induced epitaxial crystallization in silicon. PMID- 9980953 TI - Irradiation-induced amorphization of graphite. PMID- 9980954 TI - Static crossover behavior in the neighborhood of a Lifshitz point. PMID- 9980955 TI - Properties of B2O: An unsymmetrical analog of carbon. PMID- 9980956 TI - sp3 content of mass-selected ion-beam-deposited carbon films determined by inelastic and elastic electron scattering. PMID- 9980957 TI - Analysis of the x-ray-absorption near-edge-structure spectra of La1-xNdxNiO3 and LaNi1-xFexO3 perovskites at the nickel K edge. PMID- 9980958 TI - Magnetic effects in electroplasticity of metals. PMID- 9980960 TI - Ostwald ripening in disordered systems. PMID- 9980959 TI - Temperature measurements and dissociation of shock-compressed liquid deuterium and hydrogen. PMID- 9980961 TI - Optical anisotropies in chalcogenide glasses induced by band-gap light. PMID- 9980962 TI - Optical properties of ordered In0.5Ga0.5P alloys. PMID- 9980963 TI - Dimensional crossover in the effective nonlinear response in random nonlinear resistor networks. PMID- 9980964 TI - Molecular hydrogen in porous Vycor glass. PMID- 9980965 TI - Strain relaxation and self-organization phenomena in heteroepitaxial systems. PMID- 9980966 TI - Evaluation of spectroscopic properties of Yb3+-doped glasses. PMID- 9980967 TI - Lattice vibrations in Yb-pnictide compounds. PMID- 9980968 TI - Ionic transport in crystalline SiO2: The role of alkali-metal ions and hydrogen impurities. PMID- 9980969 TI - Elastic strain energy of inhomogeneous solids. PMID- 9980970 TI - Normal and oblique specular reflectivity of CuGeO3. PMID- 9980971 TI - Finite-size corrections to the correlation function of the spherical model at d >= 4. PMID- 9980973 TI - Model calculation of two-ion magnetostriction in the itinerant uniaxial ferromagnet Y2Fe17. PMID- 9980972 TI - Random-exchange quantum Heisenberg chains. PMID- 9980974 TI - Effect of an oblique magnetic field on the superparamagnetic relaxation time. PMID- 9980975 TI - Magnetic impurity coupled to a strongly correlated electron system in two dimensions. PMID- 9980976 TI - Antiparallel ordered magnetic moments of heavy and light f atoms in the (U1 xTbx)Co2Ge2 solid solutions studied by neutron diffraction. PMID- 9980977 TI - Analytical study of the thermodynamic behavior of an antiferromagnetic Heisenberg model. PMID- 9980978 TI - Magnetic-field behavior of the spin-density-wave state in (TMTSF)2AsF6. PMID- 9980979 TI - Exchange mixing and soliton dynamics in the quantum spin chain CsCoCl3. PMID- 9980981 TI - Theory for the magnetic phase diagram of thin films: Role of domain formation. PMID- 9980980 TI - Strong-coupling theory for the thermodynamics of spin-1 planar magnetic chains. PMID- 9980982 TI - Relationship between weak ferromagnetism and magnetic irreversibilities in Gd2CuO4. PMID- 9980983 TI - 1H NMR observation of the critical slowing down in ammonium chloride. PMID- 9980984 TI - Magnetoresistance of CeCu2Si2: Differences and similarities to UBe13. PMID- 9980985 TI - Non-Arrhenius relaxation in micromagnetic models of systems with many degrees of freedom. PMID- 9980986 TI - Experimental determination of the magnetic phase diagram of Gd/Fe multilayers. PMID- 9980987 TI - Electrical transport in corrugated multilayered structures. PMID- 9980988 TI - Frequency of ferromagnetic resonance in ferrofluids. PMID- 9980989 TI - Magnetoelastic coupling and order parameter in the spin-Peierls system CuGeO3. PMID- 9980991 TI - Evidence for phase selectivity in excimer-laser-induced amorphization of thermally annealed Fe66Co18B15Si glassy ferromagnet. PMID- 9980990 TI - Noncollinear and collinear magnetic structures in exchange coupled Fe/Cr(001) superlattices. PMID- 9980992 TI - Anyonlike particles in three dimensions. PMID- 9980993 TI - Transport properties of Cu-O chains in Sr2CuO3+ delta. PMID- 9980994 TI - Interactions and pinning energies in the Bose glass phase of vortices in superconductors. PMID- 9980996 TI - Calculation of the magnetic flux density distribution in type-II superconductors with finite thickness and well-defined geometry. PMID- 9980995 TI - Sodium dimers on the surface of liquid 4He. PMID- 9980997 TI - Quantum effects in a superconducting-glass model. PMID- 9980998 TI - Coherence lengths for three-dimensional superconductors in the BCS-Bose picture. PMID- 9980999 TI - Pairing in a tight-binding model with occupation-dependent hopping rate: Exact diagonalization study. PMID- 9981000 TI - Specific-heat analysis of rare-earth transition-metal borocarbides: An estimation of the electron-phonon coupling strength. PMID- 9981001 TI - Quantum phase transitions of interacting bosons and the supersolid phase. PMID- 9981002 TI - Pairing correlations with s* and dx2-y2 symmetry in a disordered Cu4O8 cluster. PMID- 9981004 TI - Effect of the non-s-wave phase shifts of the impurity potential in a d-wave superconductor. PMID- 9981003 TI - Signatures of the electron-phonon interaction in the far-infrared. PMID- 9981006 TI - s- and d-wave mixing in high-Tc superconductors. PMID- 9981005 TI - Charge-transfer excitations in the cuprate superconductors. PMID- 9981007 TI - Observation of variable-range hopping up to 900 K in the YLaxBa2-xCu3O7- delta system. PMID- 9981009 TI - Excitation spectrum of the attractive Hubbard model. PMID- 9981008 TI - Quasiparticle spectrum in superconducting YBa2Cu3O7. PMID- 9981010 TI - Superconductivity at 55 K in La0.7Sr1.3Cu(O,F)4+ delta with reduced CuO2 sheets and apical anions. PMID- 9981012 TI - Normal-state transport properties of slightly overdoped YBa2Cu3Oy crystals prepared by a crystal-pulling technique. PMID- 9981011 TI - Superconductor superlattice model for small-angle grain boundaries in Y-Ba-Cu-O. PMID- 9981013 TI - Magnetic and pair correlations of the Hubbard model with next-nearest-neighbor hopping. PMID- 9981015 TI - Trace map, Cantor set, and the properties of a three-component Fibonacci lattice. PMID- 9981014 TI - Far-infrared spectroscopy study of an uncoupled mode in a two-dimensional photonic lattice. PMID- 9981016 TI - Frequency dependence of the hopping magnetoconductivity in disordered systems. PMID- 9981018 TI - Multiple-scattering approach to the s-f model in ferromagnetic semiconductors above the Curie temperature. PMID- 9981017 TI - Use of hydrostatic pressure to resolve phonon replicalike features in the photoluminescence spectrum of beryllium-doped silicon. PMID- 9981019 TI - Incorporation of incompleteness in the k PMID- 9981020 TI - Thermal and electrical properties of the Ge:Sb:Te system by photoacoustic and Hall measurements. PMID- 9981021 TI - Fermi-level pinning of Ag on Si(111)-(7 x 7). PMID- 9981022 TI - Analytic modeling of the conductance in quantum point contacts with large bias. PMID- 9981023 TI - Irradiation-induced defect states in epitaxial n-type Si1-xGex alloy layers. PMID- 9981024 TI - Hydrogen adsorption on the GaAs(001)-(2 x 4) surface: A scanning-tunneling microscopy study. PMID- 9981025 TI - Interface-induced localization in AlSb/InAs heterostructures. PMID- 9981026 TI - Quasi-one-dimensional structures and metallization for the deposition of K on GaAs(100) As-rich surfaces. PMID- 9981027 TI - Quantum regime for in-plane magnetoresistance of double quantum wells. PMID- 9981029 TI - Edge structure of fractional quantum Hall systems from density-functional theory. PMID- 9981028 TI - Magnetophotoluminescence measurement of the formation time of an exciton in AlxGa1-xAs/GaAs quantum-well structures. PMID- 9981030 TI - Surface superstructures of quasi-one-dimensional organic conductor beta -(BEDT TTF)2PF6 crystal studied by scanning tunneling microscopy. PMID- 9981032 TI - Bragg diffraction peaks in x-ray diffuse scattering from multilayers with rough interfaces. PMID- 9981031 TI - Symmetric and asymmetric fission of metal clusters. PMID- 9981033 TI - Surface energy and stability of stress-driven discommensurate surface structures. PMID- 9981034 TI - Pairing in alkaline-earth-metal-doped fullerenes. PMID- 9981035 TI - Dwell time and asymptotic behavior of the probability density. PMID- 9981036 TI - Restricted electron motion in a one-dimensional organic conductor: Pulsed gradient spin-echo ESR in (fluoroanthene)2PF6. PMID- 9981037 TI - Wake potential of a charged particle in a strongly coupled two-dimensional electron gas. PMID- 9981038 TI - Optical reflectivity and carrier localization in incommensurate misfit layer compounds (MS)xTaS2 (M=rare-earth metal, Pb, Sn). PMID- 9981039 TI - Electronic structure of NbxMo100-x solid solutions. PMID- 9981040 TI - Charge-spin separation in 2D Fermi systems: Singular interactions as modified commutators, and solution of the 2D Hubbard model in the bosonized approximation. PMID- 9981041 TI - Extension of a local-orbital density-functional method to transition metals: Application to Pt(110) surface relaxation. PMID- 9981042 TI - Microscopic theory of the pseudogap and Peierls transition in quasi-one dimensional materials. PMID- 9981043 TI - Unoccupied states and charge transfer in Cu-Pd alloys studied by bremsstrahlung isochromat spectroscopy, x-ray photoelectron spectroscopy, and LIII absorption spectroscopy. PMID- 9981044 TI - Aharonov-Bohm oscillations in a one-dimensional Wigner crystal ring. PMID- 9981045 TI - Partial spectral weights of disordered Cu-Au alloys. PMID- 9981046 TI - Generalized local approximation to the exchange potential. PMID- 9981047 TI - Temperature dependence of the far-infrared reflectance spectra of Si:P near the metal-insulator transition. PMID- 9981049 TI - Bulk electronic structure of Ce compounds studied by x-ray photoemission and x ray absorption spectroscopies. PMID- 9981048 TI - Theory of Anderson localization in an electric field. PMID- 9981050 TI - Identification of the 1.19-eV luminescence in hexagonal GaN. PMID- 9981051 TI - Parity issues, stress results, and oscillator strengths of the rotational tunneling (H,Be) and (D,Be) complexes in silicon: The rigid rotor in a tetrahedral field. PMID- 9981052 TI - Photoluminescence mechanism in hydrogenated amorphous silicon studied by frequency-resolved spectroscopy. PMID- 9981053 TI - Properties of intrinsic point defects in silicon determined by zinc diffusion experiments under nonequilibrium conditions. PMID- 9981054 TI - Free-exciton states in crystalline GaTe. PMID- 9981055 TI - Self-interaction corrections in semiconductors. PMID- 9981056 TI - Vacancy model for substitutional Ni-, Pd-, Pt-, and Au0 in silicon. PMID- 9981057 TI - Sn submonolayer-mediated Ge heteroepitaxy on Si(001). PMID- 9981058 TI - Ultrahigh-magnetic-field cyclotron resonance in a two-dimensional electron gas at the grain boundary of Hg1-x-yCdxMnyTe. PMID- 9981059 TI - Absorption of Li on the Si(100)2 x 1 surface studied with high-resolution core level spectroscopy. PMID- 9981061 TI - Time-resolved photoluminescence of pseudomorphic SiGe quantum wells. PMID- 9981060 TI - As overlayer on GaAs(110) studied with photoemission. PMID- 9981062 TI - Exciton localization by a fractional monolayer of ZnTe inserted in a wide CdTe quantum well. PMID- 9981063 TI - Energy-selective reaction of the hydrogen-passivated Si surface with carbon tetrafluoride via dissociative electron attachment. PMID- 9981064 TI - Magnetoconductance oscillations in periodically modulated quasi-one-dimensional electron systems. PMID- 9981065 TI - Elasticity-based theory of misfit-induced structural defects at semiconductor interfaces. PMID- 9981066 TI - Bound states of a negative test charge due to many-body effects in the two dimensional electron gas. PMID- 9981067 TI - Coulomb-blockade oscillations in a quantum dot strongly coupled to leads. PMID- 9981069 TI - Simulation of a lattice model for the evolution of Si(001) surfaces exposed to oxygen at elevated temperatures. PMID- 9981068 TI - Network model of localization in a random magnetic field. PMID- 9981070 TI - Elastic light scattering from semiconductor structures: Localized versus propagating intermediate electronic excitations. PMID- 9981071 TI - Theory of strong inelastic cotunneling. PMID- 9981072 TI - Surface morphology of Ge(001) during etching by low-energy ions. PMID- 9981073 TI - Properties of the yellow luminescence in undoped GaN epitaxial layers. PMID- 9981075 TI - Low-energy vibrations at the InSb(110) surface. PMID- 9981074 TI - Low-temperature nonequilibrium transport in a Luttinger liquid. PMID- 9981076 TI - Fermi-liquid analysis on a Wolff model for resonant tunneling through a single quantum level. PMID- 9981077 TI - Family of low-energy elongated Sin (n <= 50) clusters. PMID- 9981078 TI - Reflectance anisotropy of the GaAs(001) (2 x 4) surface: Ab initio calculations. PMID- 9981079 TI - Effects of screening on the Hofstadter butterfly. PMID- 9981080 TI - Direct measurement of the free-energy barrier to nucleation from the size distribution of dendritic crystallites in a-Si thin films. PMID- 9981081 TI - Bragg-confining structures with conventional and effective-mass superlattices. PMID- 9981083 TI - Transfer-energy-dependent escape rate of electrons influenced by dynamical flux fields. PMID- 9981082 TI - Insensitivity to time-reversal symmetry breaking of universal conductance fluctuations with Andreev reflection. PMID- 9981084 TI - Quantum Hall effect in the presence of an antidot potential. PMID- 9981085 TI - Kinetics of interlayer transport prior to nucleation. PMID- 9981086 TI - p(n x 1) superstructures of Pb on Cu(110). PMID- 9981087 TI - Detachment effects during homoepitaxial growth of compact islands. PMID- 9981088 TI - Observation of two successive quantum supershells in a 15 000-electron fermionic system. PMID- 9981089 TI - Anisotropic thermal displacements of adsorbed atoms and molecules on surfaces studied by low-energy electron diffraction. PMID- 9981090 TI - X-ray structure analysis on alkali metals adsorbed on Ge(001)(2 x 1). PMID- 9981091 TI - Energetics of steps on Pt(111). PMID- 9981092 TI - Small-angle x-ray scattering under grazing incidence: The cross section in the distorted-wave Born approximation. PMID- 9981093 TI - Effective particle-hole interaction and the optical response of simple-metal clusters. PMID- 9981094 TI - Growing wetting films: An x-ray study. PMID- 9981095 TI - Theory of sputter yield fluctuations and calculation of the variance. PMID- 9981096 TI - Surface-dimer and bulk-atom imaging of the Si(001) (2 x 1) surface by Kikuchi electron holography. PMID- 9981097 TI - Effect of isotopic disorder on the Fu modes in crystalline C60. PMID- 9981098 TI - Sum-frequency generation on isotropic surfaces: General phenomenology and microscopic theory for jellium surfaces. PMID- 9981099 TI - Electron emission via Auger-ion neutralization at surfaces with adsorbed alkali metal submonolayers. PMID- 9981100 TI - Diffusion in a generalized (dense and mobile) model of a lattice gas. PMID- 9981101 TI - Diffusion coefficient for interacting lattice gases: Repulsive interactions. PMID- 9981102 TI - Model calculation of the charge transfer in low-energy He+ scattering from metallic surfaces. PMID- 9981103 TI - Comment on "Gutzwiller approximation in the Fermi hypernetted-chain theory" PMID- 9981104 TI - Erratum: Tetrahedral structures and phase transitions in III-V semiconductors PMID- 9981106 TI - Erratum: Theoretical study of strained thin quantum wells grown on vicinal surfaces PMID- 9981105 TI - Erratum: Exact solutions for barrier D- states at high magnetic fields PMID- 9981108 TI - Erratum: Optical measurements of electronic band structure in tensile strain (Ga,In)P-(Al,Ga,In)P quantum wells PMID- 9981107 TI - Erratum: Structure of negatively charged muonium in n-type GaAs PMID- 9981109 TI - Polarization and dynamical charge of ZnO within different one-particle schemes. PMID- 9981111 TI - Evidence for deterministic chaos as the origin of electrical tree breakdown structures in polymeric insulation. PMID- 9981110 TI - Direct observation of a narrow band near the gap edge of FeSi. PMID- 9981112 TI - Strong optical nonlinearities in porous silicon: Femtosecond nonlinear transmission study. PMID- 9981114 TI - Theory for quantum-dot quantum wells: Pair correlation and internal quantum confinement in nanoheterostructures. PMID- 9981113 TI - External-field-induced electric dipole moment of biexcitons in a semiconductor. PMID- 9981115 TI - Theory of the adatom-induced reconstruction of the SiC(0001) sqrt 3 x sqrt 3 surface. PMID- 9981116 TI - Symmetry-breaking instabilities in symmetric coupled-quantum-dot structures. PMID- 9981117 TI - Effect of surface termination on the electrical conductivity and broad-band internal infrared reflectance of a diamond (110) surface. PMID- 9981118 TI - Carrier-distribution-dependent band-gap renormalization in modulation-doped quantum wells. PMID- 9981120 TI - Resonant tunneling through two impurities in disordered barriers. PMID- 9981119 TI - Room-temperature conductance spectroscopy of CdSe quantum dots using a modified scanning force microscope. PMID- 9981121 TI - MBE growth and study of strain-compensated AlzGa1-z-xInxAs/AluGa1-u-vInvAs/InP quantum wells. PMID- 9981122 TI - Valence-band physics and the optical properties of GaN epilayers grown onto sapphire with wurtzite symmetry. PMID- 9981123 TI - Composite fermions and Landau-level mixing in the fractional quantum Hall effect. PMID- 9981124 TI - Response function of a two-dimensional electron gas in a unidirectional periodic potential. PMID- 9981125 TI - Transport in an inhomogeneous interacting one-dimensional system. PMID- 9981126 TI - Landau-level mixing and extended states in the quantum Hall effect. PMID- 9981127 TI - One-dimensional band structures: Rare gases on Pt(110)1 x 2. PMID- 9981129 TI - Nonlinear plasmon response in highly excited metallic clusters. PMID- 9981128 TI - X-ray diffuse-scattering study of interfacial morphology and conformal roughness in metallic multilayers. PMID- 9981130 TI - Misfit accommodation in heteroepitaxy by inclined stacking faults. PMID- 9981131 TI - Atom-specific surface magnetometry. PMID- 9981132 TI - Fundamental studies on the structures and properties of some B12-based crystals. PMID- 9981133 TI - Effects of quantum fluctuations on the photoinduced midgap absorption in an MX chain complex PMID- 9981135 TI - Electron relaxation in the conduction band of wide-band-gap oxides. PMID- 9981134 TI - Inelastic processes versus diffraction effects: Polar-angle energy-loss spectra of the graphite K edge. PMID- 9981136 TI - Electrons in extended systems. PMID- 9981137 TI - Midgap states in doped Mott insulators in infinite dimensions. PMID- 9981138 TI - Linked-cluster expansion around mean-field theories of interacting electrons. PMID- 9981140 TI - Electronic structure and superconductivity in strongly correlated systems in the pseudogap regime. PMID- 9981139 TI - From the atomic limit to a metal-insulator transition in the Hubbard model. PMID- 9981141 TI - Exact exchange potential band-structure calculations for simple metals: Li, Na, K, Rb, and Ca. PMID- 9981142 TI - Excitons in C60 studied by temperature-dependent optical second-harmonic generation. PMID- 9981143 TI - Low-temperature electron mobility studied by cyclotron resonance in ultrapure GaAs crystals. PMID- 9981144 TI - Composition and temperature-induced effects on the phonon spectra of narrow-band gap Hg1-xCdxTe. PMID- 9981146 TI - Length mismatch in random semiconductor alloys. IV. General multinary compounds. PMID- 9981145 TI - Deep-center photoluminescence in nitrogen-doped ZnSe. PMID- 9981147 TI - Low-energy Raman scattering from Co2+ electronic transitions in CdS:Co. PMID- 9981148 TI - Magnetopolaron effect on the donor transition energies in ZnSe. PMID- 9981149 TI - Warm-electron power loss in GaAs/Ga1-xAlxAs multiple quantum wells: Well-width dependence. PMID- 9981150 TI - {111} defects in 1-MeV-silicon-ion-implanted silicon. PMID- 9981151 TI - Ab initio study of hydrogen adsorption on the Si(111)-(7 x 7) surface. PMID- 9981152 TI - Photocarrier recombination in AlyIn1-yAs/AlxGa1-xAs self-assembled quantum dots. PMID- 9981153 TI - Electronic transport in nanostructures consisting of magnetic barriers. PMID- 9981154 TI - Free-carrier effects on the excitonic absorption of n-type modulation-doped Zn1 xCdxSe/ZnSe multiple quantum wells. PMID- 9981155 TI - Two-dimensional states at the HgTe/Hg0.05Cd0.95Te interface as determined from the tunneling investigations. PMID- 9981156 TI - Theory of electromagnetic response and collective excitations in antidots. PMID- 9981157 TI - Dimer-vacancy defects on the Si(001)-2 x 1 and the Ni-contaminated Si(001)-2 x n surfaces. PMID- 9981159 TI - Self-interaction-corrected density-functional theory of subband renormalization in semiconductor quantum wells. PMID- 9981158 TI - Quantum Boltzmann equation of composite fermions interacting with a gauge field. PMID- 9981160 TI - Ultrafast relaxation and transfer of charge carriers in type-II heterodoping (n-i p-i) superlattices. PMID- 9981162 TI - Two-dimensional electrons in lateral magnetic superlattices. PMID- 9981161 TI - Excitonic superradiance to exciton-polariton crossover and the pole approximations. PMID- 9981163 TI - GaAs(110) surface electronic structure by metastable deexcitation spectroscopy. PMID- 9981164 TI - Conductance and its fluctuations in disordered systems: Scaling behavior from a ballistic to localized limit. PMID- 9981165 TI - Coexistence of the Franz-Keldysh and Wannier-Stark effect in semiconductor superlattices. PMID- 9981166 TI - Collapse of spin splitting in the quantum Hall effect. PMID- 9981167 TI - Hydrogen interaction with Sb-terminated GaAs and InP (110) surfaces. PMID- 9981168 TI - Spectral and transport characteristics of an arbitrarily bent planar quantum electron guide. PMID- 9981169 TI - Contacts and edge-state equilibration in the fractional quantum Hall effect. PMID- 9981170 TI - Unified approach to electron transport in double-barrier structures. PMID- 9981171 TI - Statistics of prelocalized states in disordered conductors. PMID- 9981173 TI - Theoretical studies of multishell fullerenes. PMID- 9981172 TI - Temporal dynamics of a magnetoexciton in a quantum well. PMID- 9981174 TI - Positronium formation and the phases of two-dimensional oxygen physisorbed on graphite. PMID- 9981175 TI - Indium-induced layer-by-layer growth and suppression of twin formation in the homoepitaxial growth of Cu(111). PMID- 9981176 TI - Electronic structure of ultrathin ordered iron oxide films grown onto Pt(111). PMID- 9981178 TI - Equilibration of crystal surfaces. PMID- 9981177 TI - Binding of electrons to the surface of helium clusters. PMID- 9981179 TI - Theoretical study of the stability of beryllium oxide (110) and (001) surfaces in dense wurtzite and layered graphitic phases. PMID- 9981180 TI - Silica-aerogel thermal expansion induced by submonolayer helium adsorption. PMID- 9981181 TI - Grazing-incidence neutron diffraction by thin films with resonance enhancement. PMID- 9981182 TI - Neutron and x-ray scattering off atomic clusters. PMID- 9981183 TI - High-quality epitaxial growth of gamma -alumina films on alpha -alumina sapphire induced by ion-beam bombardment. PMID- 9981184 TI - Calculation of effective Coulomb interaction for Pr3+, U4+, and UPt3. PMID- 9981185 TI - First-principles calculations of the Coulomb pseudopotential micro*: Application to Al. PMID- 9981186 TI - Fullerene nanotubes in electric fields. PMID- 9981187 TI - Optical gap of CuO. PMID- 9981189 TI - Effect of nonlocal corrections to the local-density approximation on total-energy calculations of K, Rb, and Cs. PMID- 9981188 TI - Effect of k-space integration on self-consistent surface magnetic anisotropy calculations. PMID- 9981190 TI - Exciton magnetophotoluminescence affected by magnetic polarons and alloy fluctuations in Cd1-xMnxTe. PMID- 9981191 TI - Origin and nature of the band gap in beta -FeSi2. PMID- 9981192 TI - Cathodoluminescence from interband transitions in germanium (111) and gallium arsenide (100) crystals. PMID- 9981193 TI - Impact ionization rate in ZnS. PMID- 9981194 TI - Role of d electrons in the zinc-blende semiconductors ZnS, ZnSe, and ZnTe. PMID- 9981195 TI - Optical absorption near the fundamental absorption edge in GaSb. PMID- 9981196 TI - Transition behavior from coupled to uncoupled CdTe/ZnTe asymmetric double quantum wells. PMID- 9981197 TI - Anomalous quenching of photoemission from bulk states by deposition of Cs on InAs(100). PMID- 9981198 TI - Direct optical transitions in indirect semiconductors: The case of Ge twinning superlattices. PMID- 9981199 TI - Defectlike nature of the interface in AB/CD-type superlattices. PMID- 9981200 TI - Scanning-tunneling-microscopy study of Pb on Si(111). PMID- 9981201 TI - Temperature dependence of the shallow-donor bound-exciton-emission linewidth in high-purity InP. PMID- 9981202 TI - Interface phonons in spherical GaAs/AlxGa1-xAs quantum dots. PMID- 9981203 TI - Exciton recombination dynamics in InxGa1-xAs/GaAs quantum wells. PMID- 9981204 TI - Short-range correlation in a two-dimensional electron gas. PMID- 9981205 TI - Emission of transverse acoustic phonons by two-dimensional electrons due to heterointerface vibrations. PMID- 9981206 TI - Effect of a parallel magnetic field on the resonant-tunneling current through a quantum wire. PMID- 9981207 TI - Scattering matrix of a three-terminal junction in one dimension. PMID- 9981208 TI - Angular pinning and domain structure of a two-dimensional Wigner crystal in a III V semiconductor. PMID- 9981210 TI - Three-dimensional energy band in stage-1 acceptor graphite intercalation compounds. PMID- 9981211 TI - Electronic states and stability of selenium clusters. PMID- 9981209 TI - Charge accumulation in the two-dimensional electron gas emitter of a resonant tunneling diode. PMID- 9981212 TI - Quantitative structural analysis of fcc Fe(2 x 1) on Cu(001): A medium-energy ion scattering study. PMID- 9981213 TI - Surface structural transformations during ammonia oxidation on Rh(110). PMID- 9981214 TI - Work function and surface energy of optimized lithium slabs. PMID- 9981215 TI - Electronic-structure-induced deformations of liquid metal clusters. PMID- 9981216 TI - Up-converted luminescence and excited-state excitation spectroscopy of Cr4+ ions in forsterite. PMID- 9981217 TI - Effects of electrostatic field on the phase properties of mixed-stack organic charge-transfer compounds. PMID- 9981218 TI - Electronic structure of the semimetals Bi and Sb. PMID- 9981219 TI - Phase transition and electron localization in 1T-TaS2. PMID- 9981220 TI - 3d-resonance-photoemission study of CeB6 and PrB6. PMID- 9981221 TI - Gauge properties of k PMID- 9981222 TI - Band theory of linear and nonlinear susceptibilities of some binary ionic insulators. PMID- 9981224 TI - Electronic structure approach for complex silicas. PMID- 9981223 TI - Solution of the Boltzmann equation for multilayer systems. PMID- 9981225 TI - Theoretical zero-temperature phase diagram for neptunium metal. PMID- 9981227 TI - Anderson localization in anisotropic electronic systems under the influence of weak external electric and magnetic fields. PMID- 9981226 TI - Total-energy global optimizations using nonorthogonal localized orbitals. PMID- 9981228 TI - Gaps in the Heisenberg-Ising model. PMID- 9981229 TI - Photochemical reactions in GeO2-SiO2 glasses induced by ultraviolet irradiation: Comparison between Hg lamp and excimer laser. PMID- 9981230 TI - Deep-acceptor-mediated photoquenching of the midgap donor EL2 in semi-insulating GaAs. PMID- 9981231 TI - Structural and electronic properties of trans-polysilene (SiH)x: Many-body perturbation theory versus density-functional methods. PMID- 9981232 TI - EPR spectra and magnetization of Eu2+ ions in PbSe. PMID- 9981233 TI - Electron-hole interaction effects in the absorption spectra of phenylene-based conjugated polymers. PMID- 9981235 TI - Nonlinear response and driven chaos in n-type GaAs compensated with Ni impurities. PMID- 9981234 TI - Defect-induced absorption-band-edge values in beta -FeSi2. PMID- 9981236 TI - Minority-carrier-induced release of hydrogen from donors in silicon. PMID- 9981237 TI - Molecular-dynamics study of the vacancy and vacancy-hydrogen interactions in silicon. PMID- 9981238 TI - Electron correlation effects in screened hydrogenic impurity states in many valley semiconductors. PMID- 9981240 TI - Dynamic response of a two-dimensional electron gas: Exact treatment of Coulomb exchange in the random-phase approximation. PMID- 9981239 TI - Energies and structural properties of hydrogen and related defects in molecular dynamics-modeled a-Si:H. PMID- 9981241 TI - Transition from chaotic to regular behavior of electrons in a stadium-shaped quantum dot in a perpendicular magnetic field. PMID- 9981242 TI - Two-dimensional magnetic polarons: Anisotropic spin structure of the ground state and magneto-optical properties. PMID- 9981243 TI - Growth mechanism of thin silicon oxide films on Si(100) studied by medium-energy ion scattering. PMID- 9981244 TI - Influence of different phonon modes on the exciton ground-state energy in a quantum well in an electric field. PMID- 9981245 TI - Charge transport in thin films of semiconducting oligothiophenes. PMID- 9981246 TI - Breakdown of correlated diffusion in quasiballistic quantum wires at high magnetic fields. PMID- 9981247 TI - Bulk exciton polaritons in GaAs microcavities. PMID- 9981248 TI - Auger-electron diffraction in the low kinetic-energy range: The Si(111)7 x 7 surface reconstruction and Ge/Si interface formation. PMID- 9981249 TI - Ballistic-electron-emission-microscopy investigation of hot-carrier transport in epitaxial CoSi2 films on Si(100) and Si(111). PMID- 9981250 TI - Ab initio pseudopotential calculations of the band lineups at strained ZnS/ZnSe interfaces: Including the 3d electrons of Zn as valence states. PMID- 9981252 TI - Infrared absorption due to two-dimensional-electron-gas collective excitation in GaAs/AlxGa1-xAs multiple-quantum-well structures. PMID- 9981251 TI - Boundary-structure determination of Ag/Si(111) interfaces by x-ray diffraction. PMID- 9981253 TI - Adsorption of Li, Cs, and O on CdTe. PMID- 9981254 TI - Anomalous low-temperature dopant diffusivity and defect structure in Sb- and Sb/B implanted annealed silicon samples. PMID- 9981255 TI - Influence of electron temperature and carrier concentration on electron-LO-phonon intersubband scattering in wide GaAs/AlxGa1-xAs quantum wells. PMID- 9981256 TI - Joule heat in point contacts. PMID- 9981257 TI - Tunneling magnetoplasmon excitations in the semiclassical limit and integer quantum Hall regime for double-quantum-well systems. PMID- 9981258 TI - Efficient scheme for GW quasiparticle band-structure calculations with applications to bulk Si and to the Si(001)-(2 x 1) surface. PMID- 9981260 TI - Behavior of the energy gap near a commensurate-incommensurate transition in double-layer quantum Hall systems at nu =1. PMID- 9981259 TI - First-principles study of the structural properties of MgS-, MgSe-, ZnS-, and ZnSe-based superlattices. PMID- 9981261 TI - Persistent currents in a quantum ring: Effects of impurities and interactions. PMID- 9981262 TI - Nonlocal electrodynamics of arrays of quantum dots. PMID- 9981263 TI - Possible mechanism for the room-temperature stabilization of the Ge(111) T>300 degreesC phase by Ga. PMID- 9981264 TI - Tunneling of laser-generated free electrons in semiconductor double wells. PMID- 9981265 TI - Optical properties of (311)-oriented GaAs/AlAs superlattices. PMID- 9981266 TI - Analytical solutions for the optical absorption of semiconductor superlattices. PMID- 9981267 TI - Transport in quasi-two-dimensional systems under a weak magnetic field. PMID- 9981268 TI - Correlation effects in the impurity-limited mobility of quantum wires. PMID- 9981269 TI - III-V(110) surface dynamics from an ab initio frozen-phonon approach. PMID- 9981271 TI - Finite-difference approach to edge-state transport in quantum wires and multiterminal devices. PMID- 9981270 TI - Macroscopic Coulomb-blockade effect in a constant-current-driven light-emitting diode. PMID- 9981272 TI - Coupling between surface-polariton and edge-plasmon excitations in coupled finite half-plane superlattices. PMID- 9981273 TI - Theoretical investigation of Na adsorption on the Al(111) surface. PMID- 9981274 TI - Dynamic-scaling exponents and the roughening kinetics of gold electrodeposits. PMID- 9981275 TI - Ion-surface interactions in the electron-stimulated desorption of Cl+ from Cl2/Si(111)-7 x 7. PMID- 9981276 TI - Scanning-tunneling-microscope investigation of a 215-MeV Ne-irradiated graphite surface. PMID- 9981277 TI - Quenching of metal sticking by photo-oxidation of an amorphous semiconductor: Zn on GeS2. PMID- 9981278 TI - Heterodeposition on metallic surfaces: Structure and energetics in the Pd/Ag(110) and Pt/Ag(110) systems. PMID- 9981279 TI - Evidence for an inhomogeneous-homogeneous transition in the surface local electrostatic potential of K-covered Al(100). PMID- 9981280 TI - Electronic structures of C60 and C70 adsorbed on the Cu(111) surface and intramolecular STM images. PMID- 9981282 TI - Mechanism of carbon nanotube formation in the arc discharge. PMID- 9981281 TI - H2S interaction with Cu(100)-(2 sqrt 2 x sqrt 2 )R45 degrees-O: Formation of a metastable ||05 52||-sulfur surface reconstruction. PMID- 9981283 TI - Nonlinear photomagnetism of metals: Theory of nonlinear photoinduced dc current. PMID- 9981285 TI - Kinetics of nonequilibrium shape change in gold clusters. PMID- 9981284 TI - Reconstructed Sc2C84 monolayer on the Ag(111)1 x 1 surface. PMID- 9981287 TI - Structure and dynamics of the Cu(001) surface investigated by medium-energy ion scattering. PMID- 9981286 TI - Segregation profiles in Cu3Au above the order-disorder transition. PMID- 9981288 TI - Theoretical study of cubic structures based on fullerene carbon clusters: C28C and (C28)2. PMID- 9981290 TI - Adsorption-site mixing at a continuous order-disorder phase transition. PMID- 9981289 TI - Optical and electrical properties of thin films. PMID- 9981291 TI - Phonon-libron dynamics of a commensurate molecular monolayer: (2 x 1) CO2/NaCl(100). PMID- 9981292 TI - Kinetics of surface steps in the presence of impurities: Patterns and instabilities. PMID- 9981293 TI - Helium-atom-scattering study of the dispersion curves of step-localized phonons on Cu(211) and Cu(511). PMID- 9981295 TI - All-electron local and gradient-corrected density-functional calculations of Nan dipole polarizabilities for n=1-6. PMID- 9981294 TI - Stability of periodic domain structures in a two-dimensional dipolar model. PMID- 9981296 TI - Comment on "Observation of time-nonreversible optical interaction with zinc blende semiconductors" PMID- 9981298 TI - Many-body calculation of the magnetic, optical, and charge-transfer spectra of solid oxygen in the alpha and beta phases. PMID- 9981297 TI - Reply to "Comment on 'Observation of time-nonreversible optical interaction with zinc-blende semiconductors' " PMID- 9981299 TI - Electronic structure of the misfit-layer compound (SnS)1.17NbS2 deduced from band structure calculations and photoelectron spectra. PMID- 9981300 TI - Dual-space approach for density-functional calculations of two- and three dimensional crystals using Gaussian basis functions. PMID- 9981302 TI - Parameter consistency in multienergetic k PMID- 9981301 TI - Angle-resolved photoelectron spectroscopic study of oriented p-sexiphenyl: Wave number conservation and blurring in a short model compound of poly(p-phenylene). PMID- 9981303 TI - Electronic and magnetic structure of KNiF3 perovskite. PMID- 9981305 TI - Effect of hole doping on the electronic structure of Nd1-xSrxTiO3. PMID- 9981304 TI - X-ray emission, photoelectron spectra, and electronic structure of Sr2CuO2F2+ delta. PMID- 9981306 TI - Slave-particle quantization and sum rules in the t-J model. PMID- 9981307 TI - Analytic treatment of Mott-Hubbard transition in the half-filled Hubbard model and its thermodynamics. PMID- 9981308 TI - Ab initio study of antiferromagnetic rutile-type FeF2. PMID- 9981309 TI - Correct continuum limit of the functional-integral representation for the four slave-boson approach to the Hubbard model: Paramagnetic phase. PMID- 9981310 TI - Single-particle spectral density of the Hubbard model. PMID- 9981312 TI - Dynamical correlations in a Hubbard chain with a resonating-valence-bond ground state. PMID- 9981311 TI - Fermi surface of ferromagnetic fcc cobalt. PMID- 9981313 TI - Atomic screening and intersite Coulomb repulsion in strongly correlated systems. PMID- 9981315 TI - Density-functional theory on a lattice: Comparison with exact numerical results for a model with strongly correlated electrons. PMID- 9981314 TI - Calculation of elastic constants in UC, US, and UTe. PMID- 9981316 TI - Consistent thermodynamic study of the solid and liquid phases of tungsten. PMID- 9981317 TI - Midinfrared picosecond spectroscopy studies of Auger recombination in InSb. PMID- 9981318 TI - Interaction between copper and point defects in silicon irradiated with 2-MeV electrons. PMID- 9981319 TI - Real-space coupled-oscillator approach to the radiative decay of conjugated polymers. PMID- 9981320 TI - Phonon confinement in GaAs by defect formation studied by real-time Raman measurements. PMID- 9981321 TI - Band-edge dynamics and trapping in ZnSe crystals. PMID- 9981322 TI - Application of generalized gradient approximations: The diamond- beta -tin phase transition in Si and Ge. PMID- 9981323 TI - Theory of electron two-band self-trapping in atomic soft configurations: Hybridization of states, formation of negative-U centers, and anharmonic atomic dynamics. PMID- 9981324 TI - Chemisorption of Cl on the Si(100)-2 x 1 surface. PMID- 9981325 TI - Adsorption of K on Si(100)2 x 1 at room temperature studied with photoelectron spectroscopy. PMID- 9981326 TI - Trap distribution for charge carriers in poly(paraphenylene vinylene) (PPV) and its substituted derivative DPOP-PPV. PMID- 9981327 TI - Comparison between the electronic dielectric functions of a GaAs/AlAs superlattice and its bulk components by spectroscopic ellipsometry using core levels. PMID- 9981328 TI - Spectroscopy of the optical vibrational modes in GaAs/AlxGa1-xAs heterostructures with monolayer-wide AlxGa1-xAs barriers. PMID- 9981329 TI - Dynamic interaction of bulk acoustic waves with a two-dimensional electron gas at an AlxGa1-xAs/GaAs heterojunction in strong magnetic fields. PMID- 9981330 TI - Green's-function study of the electron tunneling in a double-barrier heterostructure. PMID- 9981331 TI - Quantization of excitons in CuCl epitaxial thin films: Behavior between a two dimensional quantum well and the bulk. PMID- 9981333 TI - Temperature dependence of phase breaking in ballistic quantum dots. PMID- 9981332 TI - Polarization retention in the visible photoluminescence of porous silicon. PMID- 9981334 TI - Size-mismatch disorder at the surface of semiconductors. PMID- 9981336 TI - X-ray standing-wave study of an Sb-terminated GaAs(001)-(2 x 4) surface. PMID- 9981335 TI - Smoothed density of states of electrons and smoothed frequency spectrum of phonons for a mesoscopic system. PMID- 9981337 TI - Microscopic mechanisms governing exciton-decay kinetics in type-II GaAs/AlAs superlattices. PMID- 9981339 TI - Excitons in type-II quantum dots: Finite offsets. PMID- 9981338 TI - Influence of light on the confinement potential of GaAs/AlxGa1-xAs heterojunctions. PMID- 9981340 TI - Theory of mesoscopic transport in disordered wires. PMID- 9981341 TI - Energy gaps of semiconducting nanotubules. PMID- 9981342 TI - Dynamic response and thermodynamics of mesoscopic metal rings at constant particle number. PMID- 9981343 TI - Many-electron effects on ballistic transport. PMID- 9981344 TI - W PMID- 9981346 TI - Quantum many-body states of excitons in a small quantum dot. PMID- 9981345 TI - Transmission resonances and zeros in multiband models. PMID- 9981347 TI - Antiresonant hopping conductance and negative magnetoresistance in quantum-box superlattices. PMID- 9981349 TI - Magnetotransport phenomena in periodically delta -doped structures. PMID- 9981348 TI - Linewidth analysis of the photoluminescence of InxGa1-xAs/GaAs quantum wells (x=0.09, 0.18, 1.0). PMID- 9981350 TI - Composite-fermion description of correlated electrons in quantum dots: Low-Zeeman energy limit. PMID- 9981351 TI - Ballistic transport in electron stub tuners: Shape and temperature dependence, tuning of the conductance output, and resonant tunneling. PMID- 9981352 TI - Method for calculating photo- and electroreflectance spectra from semiconductor heterostructures. PMID- 9981354 TI - Density profile in a weakly modulated two-dimensional system in a magnetic field. PMID- 9981353 TI - Oscillations in the diffusion thermopower of a two-dimensional electron gas. PMID- 9981356 TI - Directed inelastic hopping of electrons through metal-insulator-metal tunnel junctions. PMID- 9981355 TI - Rectification coefficient of a quantum dot with interacting electrons. PMID- 9981357 TI - Multiple-scattering effect of surface-plasmon polaritons in light emission from tunnel junctions. PMID- 9981358 TI - Effects of nonlocal ion pseudopotential on the electronic shell structure of metal clusters. PMID- 9981359 TI - Surface disordering without surface roughening. PMID- 9981360 TI - Generation of optical standing waves around mesoscopic surface structures: Scattering and light confinement. PMID- 9981362 TI - Effect of small-cluster mobility and dissociation on the island density in epitaxial growth. PMID- 9981361 TI - Quantum theory of infrared-reflection spectroscopy from adsorbate-covered metal surfaces in the anomalous-skin-effect frequency region. PMID- 9981363 TI - Anisotropic roughening of vicinally miscut Ag(110): X-ray-reflection profile analysis using the domain-matrix method. PMID- 9981364 TI - Incommensurate structures and epitaxial growth of Li on Ru(0001): A quantitative low-energy electron-diffraction study. PMID- 9981365 TI - Structural and electronic properties of polymeric fullerene chains. PMID- 9981366 TI - Three-dimensional reconstruction by holographic LEED: Proper identification of the reference wave. PMID- 9981367 TI - Comparison of molecular dynamics and variational transition-state-theory calculations of the rate constant for H-atom association with the diamond {111} surface. PMID- 9981368 TI - Structural determination of the S-passivated InP(100)-(1 x 1) surface by dynamical low-energy electron-diffraction analysis. PMID- 9981370 TI - Onset of d screening in alkali and alkaline earths. PMID- 9981369 TI - Influence of multiple elastic and inelastic scattering on photoelectron line shape. PMID- 9981371 TI - Linewidth of intramolecular vibrations of carbon monoxide adsorbate on metal surfaces: A possible mechanism. PMID- 9981373 TI - Multiple-scattering calculations of x-ray-absorption spectra. PMID- 9981372 TI - Nonadiabatic effects in charge transfer in atom-surface scattering. PMID- 9981374 TI - Spin-split masses and metamagnetic behavior of almost-localized fermions. PMID- 9981375 TI - Photonic band gaps in a two-dimensional graphite structure. PMID- 9981376 TI - Change of electronic properties on the doping-induced insulator-metal transition in La1-xSrxVO3. PMID- 9981378 TI - Real-space adaptive-coordinate electronic-structure calculations. PMID- 9981377 TI - Mixed-space formalism for the dielectric response in periodic systems. PMID- 9981379 TI - Effect of non-Ohmic back contacts in capacitance transient measurements on hydrogenated amorphous silicon. PMID- 9981380 TI - Charge-density-wave dynamics in the molecular conductor (perylene)2Pt(mnt)2 (mnt=maleonitriledithiolate). PMID- 9981381 TI - Suppression of the Auger recombination due to spin polarization of excess carriers and Mn2+ ions in the semimagnetic semiconductor Cd0.95Mn0.05S. PMID- 9981382 TI - Dependence of the electron mobility on the acceptor concentration in Si delta doped GaAs. PMID- 9981384 TI - Surface reconstructions of zinc-blende GaN/GaAs(001) in plasma-assisted molecular beam epitaxy. PMID- 9981383 TI - Band-structure analysis of the conduction-band mass anisotropy in 6H and 4H SiC. PMID- 9981385 TI - Stochastic resonance and nonlinear response in double-quantum-well structures. PMID- 9981386 TI - Excitons in high magnetic fields in disordered two-dimensional systems: Weak localization effects for composite neutral particles. PMID- 9981387 TI - Evidence for a photocurrent Fano resonance in an artificial nanostructure. PMID- 9981388 TI - Reconstruction of the GaAs(001) surface induced by submonolayer Si deposition. PMID- 9981390 TI - Dispersion of optical second-harmonic generation from Si(111)7 x 7. PMID- 9981389 TI - Temperature dependence of the free-exciton-emission linewidth in high-purity InP. PMID- 9981391 TI - Accommodation of strain in ultrathin InAs/GaAs films. PMID- 9981393 TI - Time-resolved nonlinear luminescence of biexcitons in ZnSe-ZnxMg1-xSySe1-y single quantum wells. PMID- 9981392 TI - Nanocrystalline Ge filaments in the pores of a mesosilicate. PMID- 9981395 TI - Zero-bias anomaly of tunneling into the edge of a two-dimensional electron system. PMID- 9981394 TI - Crossover from global to local rule for the Coulomb blockade in small tunnel junctions. PMID- 9981396 TI - Ballistic conductance of composite fermions. PMID- 9981397 TI - Nonlinear calculation of the stopping power of a two-dimensional electron gas for heavy particles. PMID- 9981398 TI - Strong-confinement approach for impurities in quantum dots. PMID- 9981399 TI - Direct structure determination of a composite double-layer surface alloy by x-ray photoelectron diffraction: p(2 x 2)-Na/Al(111). PMID- 9981400 TI - Spin dynamics of triplet photoexcitations in C60: Evidence for a dynamic Jahn Teller effect. PMID- 9981401 TI - The Hofstadter spectrum of the Wigner crystal. PMID- 9981402 TI - X-ray-reflectivity fine structure and EXAFS. PMID- 9981403 TI - Radiation effects on Li-vacancy ordering in beta -LiAl. PMID- 9981404 TI - Melting maximum in alkali metals. PMID- 9981406 TI - Mass transport in ionic crystals induced by the ponderomotive action of a high frequency electric field. PMID- 9981405 TI - Decimation studies of Bloch electrons in a magnetic field: Higher-order limit cycles underlying the phase diagram. PMID- 9981408 TI - Estimation of the intrinsic magnetic susceptibility of Y1-xUxPd3 and UCu5-xPdx. PMID- 9981407 TI - One-dimensional Ising model with long-range interactions: A renormalization-group treatment. PMID- 9981409 TI - Giant magnetoresistance in Cr100-xFex bulk granular alloys. PMID- 9981410 TI - Determination of magnetic anisotropy in Fe/Cu multilayers: Equivalence of dynamic and static measurements. PMID- 9981411 TI - Antiphase domain and magnetic interactions in partially ordered Ni3Mn. PMID- 9981412 TI - Nonmonotonic dependence of magnetic viscosity on thermal relaxation rate. PMID- 9981413 TI - Topological disorder as an origin of a magnetic moment on Mn in Al-Mn alloys. PMID- 9981414 TI - Entropy of spin models by the Monte Carlo method. PMID- 9981415 TI - Magnetism of Fe on Au(100) in the monolayer limit. PMID- 9981416 TI - Anisotropic spin-1/2 Heisenberg chain with open boundary conditions. PMID- 9981417 TI - Hall effect and magnetoresistance in Nd1.85Ce0.15CuO4- delta films. PMID- 9981419 TI - Phonon-induced d-wave pairing in the two-dimensional Hubbard model. PMID- 9981418 TI - Critical magnetic field in layered superconductors. PMID- 9981420 TI - Renormalization-group approach to the Coulomb pseudopotential for C60. PMID- 9981421 TI - Josephson current-phase relationships with unconventional superconductors. PMID- 9981422 TI - 89Y NMR and Cu NQR of hydrogenated oxygen-deficient YBa2Cu3O6.7. PMID- 9981424 TI - Properties of YbAgCu4 at high pressures and magnetic fields. PMID- 9981423 TI - Plastic energies in layered superconductors. PMID- 9981425 TI - Ferroelectric-paraelectric phase transition in KNbO3 at high pressure. PMID- 9981426 TI - Crystal structure of germanium quenched from the melt under high pressure. PMID- 9981427 TI - Effect of quenching processes on the decay of fast luminescence from barium fluoride excited by VUV synchrotron radiation. PMID- 9981428 TI - Cathodoluminescence microcharacterization of the defect structure of quartz. PMID- 9981429 TI - Dynamics of the freezing process in relaxor ferroelectrics. PMID- 9981430 TI - X-ray-absorption spectroscopy at the Fe L2,3 threshold in iron oxides. PMID- 9981431 TI - Origin of ordering in B2-type transition-metal aluminides: Comparative study of the defect properties of PdAl, NiAl, and FeAl. PMID- 9981432 TI - EPR of tungsten impurities in KTiOPO4 single crystals grown from molten tungstate solutions. PMID- 9981433 TI - Molecular-dynamics studies on the shock-induced phase transition of a MgF2 crystal. PMID- 9981435 TI - Inelastic scattering of fast electrons by crystals. PMID- 9981434 TI - Phase separation, oxygen composition, and a glass transition due to freezing-in of the oxygen rearrangement in La2NiO4.094 single crystals. PMID- 9981436 TI - Distribution of K ions in intermediate KC60. PMID- 9981437 TI - X-ray-absorption spectroscopy investigation of the martensitic structural transformation in the RCu (R=rare earth) series. PMID- 9981438 TI - Phase diagrams of the Blume-Emery-Griffiths model for semiconducting alloy systems (ABD2)1-x(CD)2x or PMID- 9981439 TI - Structural and electrical transport properties of Al-Cu-Cr quasicrystals. PMID- 9981441 TI - Effects of synthesis conditions on existence and nonexistence of the ArF excimer laser and x-ray induced B2 alpha band in type-III fused silicas. PMID- 9981440 TI - Effect of variation in the glass-former network structure on the relaxation properties of conductive Ag+ ions in AgI-based fast ion conducting glasses. PMID- 9981443 TI - Theory of electron energy loss in a random system of spheres. PMID- 9981442 TI - Characterization of free volume in atomic models of metallic glasses. PMID- 9981444 TI - Hamiltonian map approach to resonant states in paired correlated binary alloys. PMID- 9981446 TI - Observation of transitionlike behavior and a slow thermal relaxation process in icosahedral quasicrystals. PMID- 9981445 TI - Phonon modes and vibrational entropy of mixing in Fe-Cr. PMID- 9981447 TI - Molecular-dynamics study of orientational order in liquids and glasses and its relation to the glass transition. PMID- 9981448 TI - Energy transfer within a regular distribution of donors and acceptors: Application to the upconversion dynamics of Er3+:YAlO3 and Er3+:YAG. PMID- 9981449 TI - Phonon densities of states and vibrational entropies of ordered and disordered Ni3Al. PMID- 9981451 TI - Correlated squeezed-state approach for a dissipative two-state system. PMID- 9981450 TI - Evaluation of the displacement-displacement correlation function of a one dimensional crystal: A comparison of the results of perturbation theory with the Mori-Dupuis method. PMID- 9981452 TI - Strongly nonlinear response of fractal clusters. PMID- 9981454 TI - Theory of nuclear resonant scattering of synchrotron radiation in the presence of diffusive motion of nuclei. PMID- 9981453 TI - Raman scattering from fractals: Simulation on large structures by the method of moments. PMID- 9981455 TI - Ultrafast vibrational dynamics by time-delayed nondegenerate optical four-wave mixing in condensed matter. PMID- 9981457 TI - Quantum heat-bath theory of dechanneling. PMID- 9981456 TI - Fractal versus quasiclassical diffusive transport in a class of quantum systems. PMID- 9981458 TI - Theoretical study on quantum effects in triangular antiferromagnets with axial anisotropy using the numerically constructed Bogoliubov transformation for magnons. PMID- 9981459 TI - Optical-absorption bands by exciton-magnon coupling in quasi-two-dimensional antiferromagnets (CnH2n+1NH3)2MnCl4 (n=1,2,3). PMID- 9981460 TI - 63,65Cu NMR and NQR study of the Cu2+ electronic state and the spin dynamics in the spin-Peierls compound CuGeO3. PMID- 9981461 TI - Xenon on ferromagnetic surfaces: A spin-resolved photoemission study. PMID- 9981462 TI - Magnetoresistance in GeAu thin films exhibiting variable-range-hopping conductivity. PMID- 9981463 TI - Thermodynamic and magnetic properties of the S=1 Heisenberg chain Ni(C2H8N2)2Ni(CN)4: Experiments and theory. PMID- 9981464 TI - Magnetic properties of nanostructured CoSm/FeCo films. PMID- 9981465 TI - Oscillatory magnetism in compounds of iron with 4d metals. PMID- 9981466 TI - Low-temperature magnetoresistance of gamma -phase FexNi80-xCr20 alloys near the critical composition for ferromagnetism. PMID- 9981467 TI - Magnetoresistance properties of thin films of the metallic oxide ferromagnet SrRuO3. PMID- 9981468 TI - Magnetic aftereffect experiments at low temperature: Linear response and quantum noise. PMID- 9981469 TI - Magnetic properties of Gd-Y alloys: Regularities and anomalies. PMID- 9981470 TI - Thermoremanent magnetization as a probe of the field-quenched states in spin glasses. PMID- 9981471 TI - Simultaneous thermodynamic and transport measurements of the field-induced spin density-wave transitions in (TMTSF)2ClO4. PMID- 9981473 TI - Effects of realistic band structures on the interlayer coupling strengths in magnetic multilayers. PMID- 9981472 TI - Stochastic resonance and phase shifts in superparamagnetic particles. PMID- 9981474 TI - Magnetic transitions in triangular antiferromagnets with distorted exchange structure. PMID- 9981475 TI - Phase transition, longitudinal spin fluctuations, and scaling in a two-layer antiferromagnet. PMID- 9981476 TI - Discovery of a spin-singlet ground state with an energy gap in CaCuGe2O6. PMID- 9981477 TI - Thermal relaxation in arrays of coupled ferromagnetic particles. PMID- 9981478 TI - Magnetic phase transition in the metal-rich rare-earth carbide halides Gd2XC (X= Br,I). PMID- 9981479 TI - Surface and bulk magnetic properties of pyrite NiS2: Magnetization and neutron scattering studies. PMID- 9981481 TI - Formation of the Haldane phase by soliton-pair dissociation: Results from a cluster approximation. PMID- 9981480 TI - Relativistic calculations of the magneto-optical Kerr spectra in (001) and (111) US, USe, and UTe. PMID- 9981482 TI - Anisotropic magneto-optical Kerr effect of hcp and fcc Co from first principles. PMID- 9981483 TI - Cooperative ordering of holes and spins in La2NiO4.125. PMID- 9981484 TI - Superfluid Rayleigh criterion. PMID- 9981485 TI - Optical observation of thermohydrodynamic flow in thin layers of superfluid 4He with a free surface. PMID- 9981486 TI - Terahertz transmission of a Ba1-xKxBiO3 film probed by coherent time-domain spectroscopy. PMID- 9981487 TI - Thermal conductivity of type-II superconductors in the mixed state: Electron vortex scattering. PMID- 9981488 TI - Scattering mechanisms in Rb-doped single-crystal C60. PMID- 9981489 TI - Quantum fluctuations in superconducting arrays with a general capacitance matrix. PMID- 9981490 TI - Tunneling, relaxation of spin-polarized quasiparticles, and spin-charge separation in superconductors. PMID- 9981491 TI - Spectral properties of the two-dimensional Hubbard model. PMID- 9981492 TI - Superfluid turbulence in the low-temperature limit. PMID- 9981493 TI - Unbiased estimators in quantum Monte Carlo methods: Application to liquid 4He. PMID- 9981494 TI - Symmetries and mean-field phases of the extended Hubbard model. PMID- 9981495 TI - Magnetic and superconducting properties of single-crystal TmNi2B2C. PMID- 9981496 TI - Magnetism and superconductivity in single-crystal ErNi2B2C. PMID- 9981497 TI - Three-dimensional to two-dimensional crossover in layered high-Tc superconductors. PMID- 9981498 TI - Phonon renormalization and c-axis phonon-plasmon mixing in La2CuO4. PMID- 9981499 TI - Elastic and nonlinear acoustic properties of YBa2Cu3O7-x ceramics with different oxygen contents. PMID- 9981500 TI - Electron-spectroscopy investigation of the Bi2Sr2CaCu2O8 and Bi2Sr2CaCu2O8+y single-crystal cleaved surfaces. PMID- 9981502 TI - Magnetism of Fe, Ni, and Zn in Nd1.85Ce0.15CuO4: Comparison of experiment and theory. PMID- 9981501 TI - Fluctuational phenomenological model for the magnetodissipation in high-Tc superconductors. PMID- 9981503 TI - Magnetoconductivity in YBa2Cu3O7- delta thin films. PMID- 9981504 TI - Superconducting-state thermodynamic parameters and anisotropy of HgBa2Can-1CunOy by reversible magnetization measurements. PMID- 9981505 TI - Thermally induced dimensional crossover in single-crystal Bi2Sr2CaCu2Ox. PMID- 9981507 TI - Identifying the superconducting pairing state of high-Tc oxides by the Josephson effect. PMID- 9981506 TI - Mixed valency of Pr in a Y1-xPrxBa2Cu3O7 bilayer. PMID- 9981508 TI - Evidence for three-dimensional flux creep in thin-film Bi2Sr2CaCu2O8+ delta. PMID- 9981510 TI - Simulated flux-lattice melting and magnetic-field distributions in high-Tc superconductors. PMID- 9981509 TI - Angular dependence of microwave dissipation by vortices in YBa2Cu3O7-x thin films. PMID- 9981511 TI - Superconductivity in ultrathin quench-condensed Pb/Sb and Pb/Ge multilayers. PMID- 9981512 TI - Erratum: Magnetic susceptibility of carbon structures PMID- 9981513 TI - Modulated structure of NiTa2Se7 in its incommensurate charge-density-wave state at 16 K. PMID- 9981514 TI - Determination of potentially homogeneous-nucleation-based crystallization in o terphenyl and an interpretation of the nucleation-enhancement mechanism. PMID- 9981515 TI - Electric-field-gradient calculations on cadmium in cadmium-helium vacancy clusters in tungsten. PMID- 9981516 TI - Inhomogeneous broadening of optical transitions dominated by low-symmetry crystal field components in Cr3+-doped gallogermanates. PMID- 9981517 TI - Computer simulation of defects in KTaO3. PMID- 9981518 TI - Oxygen defects in BaFBr and BaFCl. PMID- 9981519 TI - Nonlinear dynamics of self-organized microstructure under irradiation. PMID- 9981520 TI - Homogeneous broadening and hyperfine structure of optical transitions in Pr3+:Y2SiO5. PMID- 9981521 TI - Response of helium bubbles in gold to displacement-cascade damage. PMID- 9981522 TI - Pressure-induced strong mode coupling and phase transitions in KNbO3. PMID- 9981524 TI - Infrared fundamentals and phase transitions in CO2 up to 50 GPa. PMID- 9981523 TI - Origin of the critical scattering on two length scales in SrTiO3: A high-energy synchrotron-radiation diffraction study. PMID- 9981525 TI - Molecular approach to the modeling of elasticity and piezoelectricity of SiC polytypes. PMID- 9981526 TI - Structure and ferroelasticity of the ferroelastic crystal KMnCl3. PMID- 9981527 TI - Order-disorder transformation in Fe-Al under ball milling. PMID- 9981529 TI - Model for vacancy-loop nucleation in displacement cascades. PMID- 9981528 TI - Optical transitions of the H centers in alkali halides. PMID- 9981530 TI - Structural instabilities in KTaO3 and KNbO3 described by the nonlinear oxygen polarizability model. PMID- 9981532 TI - 1H and 2H NMR studies of dynamic orientational, translational, and dipolar orders in the doubly reentrant liquid crystal 4-cyanobenzoyloxy- PMID- 9981531 TI - Defect structure in neutron-irradiated beta -6LiAl and beta -7LiAl: Electrical resistivity and Li diffusion. PMID- 9981533 TI - Structure and properties of silicon XII: A complex tetrahedrally bonded phase. PMID- 9981534 TI - Order-disorder in a model lattice-mismatched binary alloy. PMID- 9981535 TI - Unified description of the soft and the relaxational mode in the dielectric response of ferroelectrics. PMID- 9981536 TI - Monte Carlo studies of the temperature-dependent size of polyelectrolyte chains. PMID- 9981537 TI - Disorder and electronic properties of substituted perylene radical-cation salts. PMID- 9981538 TI - Structural and electronic properties of liquid boron from a molecular-dynamics simulation. PMID- 9981539 TI - Interface growth in a two-spin facilitated kinetic Ising model. PMID- 9981540 TI - Relationship between structure and conductivity in liquid carbon. PMID- 9981541 TI - Lyapunov exponent and transfer-matrix spectrum of the random binary alloy. PMID- 9981542 TI - Electron wave transport in coherently absorptive random media. PMID- 9981543 TI - Molecular-dynamics simulations of hydrogen diffusion in niobium: Influence of imperfections. PMID- 9981544 TI - Effects of static crystal field on the homogeneous width of the 5D0-7F0 line of Eu3+ and Sm2+ in solids. PMID- 9981545 TI - Time- and charge-dependent atom-atom potentials for vibronic coupling in nonequilibrium electronic states. PMID- 9981546 TI - Phonons in CuGeO3 studied using polarized far-infrared and Raman-scattering spectroscopies. PMID- 9981547 TI - Polaronic relaxation in perovskites. PMID- 9981548 TI - Motion of heavy particles coupled to fermionic and bosonic environments in one dimension. PMID- 9981549 TI - Critical parameters for the d=3 Ising model in a film geometry. PMID- 9981550 TI - Percolation effects in two-component strongly nonlinear composites: Universal scaling behavior. PMID- 9981551 TI - Quantized spin currents in two-dimensional chiral magnets. PMID- 9981553 TI - Net-charge-compensation effects on the crystal field and the spin Hamiltonian for the Fe3+ ions at the K+-vacancy sites in Fe3+:KZnF3 and Fe3+:KMgF3 crystals. PMID- 9981552 TI - 139La NQR relaxation and microSR study of Zn-doping effects in La2CuO4. PMID- 9981555 TI - Magnetic susceptibilities of V3+ in corundum: Magnetic anisotropy at high fields. PMID- 9981554 TI - Magnetic properties of a superlattice of amorphous multilayered films. PMID- 9981556 TI - Interfacial-roughness effects on giant magnetoresistance and interlayer coupling in Co/Cu superlattices. PMID- 9981557 TI - Hyperfine-enhanced nuclear polarization in NdGaO3. PMID- 9981558 TI - CeCoAl4: An incommensurate antiferromagnet. PMID- 9981559 TI - Spin dynamics in pure and Zn-doped CuGeO3 by muon spin relaxation: Spin-Peierls and spin-glass transitions. PMID- 9981560 TI - Magnetic anomalies in UPd2Ge2 induced by iron doping. PMID- 9981561 TI - Micromagnetics at a finite temperature using the ridge optimization method. PMID- 9981562 TI - Spin correlations in the two-dimensional quantum s=1/2 XY model. PMID- 9981563 TI - Gaussian, exponential, and power-law decay of time-dependent correlation functions in quantum spin chains. PMID- 9981564 TI - Evolution of a magnetic state in YbCu5-xGax. PMID- 9981565 TI - Types of temperature dependence of single-ion magnetic anisotropy constants by general thermodynamic considerations. PMID- 9981566 TI - Upsilon point in a spin model. PMID- 9981567 TI - Photoemission study of valence electrons in La(Co1-xFex)13 (x=0,0.2). PMID- 9981568 TI - Toulouse limit of the multichannel Kondo model. PMID- 9981569 TI - Domain walls in the quantum transverse Ising model. PMID- 9981571 TI - Hole dynamics in generalized spin backgrounds in infinite dimensions. PMID- 9981570 TI - Incommensurate state of CsCuCl3 in a transverse magnetic field. PMID- 9981572 TI - SU(2) coherent-state path integral for the Heisenberg ferromagnet. PMID- 9981573 TI - Resonant x-ray and neutron diffraction study of USb0.8Te0.2. PMID- 9981575 TI - Redox mechanism for the generation of holes in TlBa1-xSrxLaCuO5+ delta : A neutron-diffraction study. PMID- 9981574 TI - Bulk and surface magnetism and interplanar spacings in Gd from first-principles calculations. PMID- 9981576 TI - Critical fields of the superconducting fullerene RbCs2C60. PMID- 9981577 TI - Surface barriers, irreversibility line, and pancake vortices in an aligned HgBa2Ca2Cu3O8+ delta superconductor. PMID- 9981579 TI - Far-infrared magnetoconductivity of a high-Tc superconducting film. PMID- 9981578 TI - Inductive measurements of UPt3 in the superconducting state. PMID- 9981580 TI - Coherence effects in a normal-metal-insulator-superconductor junction. PMID- 9981581 TI - Relation between normal-state and superconductive properties of niobium sputtered films. PMID- 9981582 TI - Microwave surface impedance of proximity-coupled Nb/Al bilayer films. PMID- 9981583 TI - Mo6Se8-cluster-based superconducting compounds Cs2Mo12Se14 and Rb4Mo18Se20: Evidence for a strongly correlated and anisotropic electron system. PMID- 9981584 TI - Transport properties of a three-dimensional array of Josephson junctions in a magnetic field. PMID- 9981585 TI - Magnetic vortices in a distributed Josephson junction with electrodes of finite thickness. PMID- 9981586 TI - Monte Carlo analysis of the two-dimensional XY model. I. Self-consistent boundary conditions. PMID- 9981587 TI - Monte Carlo analysis of the two-dimensional XY model. II. Comparison with the Kosterlitz renormalization-group equations. PMID- 9981588 TI - Finite-size effects on the vortex-glass transition in thin YBa2Cu3O7- delta films. PMID- 9981589 TI - Electronic structure of the surfaces of layered copper oxides. PMID- 9981590 TI - Vortex unbinding and layer decoupling in epitaxial Bi2Sr2Ca2Cu3O10+ delta films. PMID- 9981591 TI - Properties of high-Tc Josephson junctions with Y0.7Ca0.3Ba2Cu3O7- delta barrier layers. PMID- 9981593 TI - Model of oxygen diffusion in YBa2Cu3O6+x with next-nearest-neighbor hopping: A Monte Carlo study. PMID- 9981592 TI - In-plane penetration-depth anisotropy in a d-wave model. PMID- 9981594 TI - Nonlinear U(j) dependence determined directly from low-electric-field E-js curves in YBa2Cu3O7- delta thin films. PMID- 9981595 TI - Sound attenuation by helicon modes in high-Tc superconductors. PMID- 9981596 TI - Ab initio pseudopotential calculations for the electronic structure of low-Tc LuNi2B2C and the related compound LuNiBC. PMID- 9981598 TI - Spin-density-wave transition in a two-dimensional spin liquid. PMID- 9981597 TI - Spin polarons in the t-t'-J model. PMID- 9981600 TI - Random-matrix-theory approach to the intensity distributions of waves propagating in a random medium. PMID- 9981599 TI - Comment on "Spectrum of 180 degrees Bloch-type domain-wall excitations in yttrium iron garnet" PMID- 9981601 TI - Origin of the <11/20> atomic short-range order in Au-rich Au-Fe alloys. PMID- 9981602 TI - Coulomb gap at finite temperatures. PMID- 9981603 TI - Coupled quasiparticle-boson systems: The semiclassical approximation and discrete nonlinear Schrodinger equation. PMID- 9981605 TI - Electron interaction on the giant magnetoresistance in the perpendicular geometry. PMID- 9981604 TI - Intrinsic localized spin modes in ferromagnetic chains with on-site anisotropy. PMID- 9981606 TI - Monte Carlo study of the Heisenberg antiferromagnet on the triangular lattice. PMID- 9981607 TI - Quasiparticle spectrum in a nearly antiferromagnetic Fermi liquid: Shadow and flat bands. PMID- 9981608 TI - Onset of superconductivity in the antiferromagnetically ordered state of single crystal DyNi2B2C. PMID- 9981609 TI - Supercurrent force on Andreev-reflected quasiparticles and excess currents. PMID- 9981611 TI - Transport properties of extended-s-state superconductors. PMID- 9981610 TI - Surface-barrier effects in grain-aligned HgBa2CuO4+ delta, HgBa2CaCu2O6+ delta, and HgBa2Ca2Cu3O8+ delta compounds. PMID- 9981612 TI - Superconducting phase of a two-chain Hubbard model. PMID- 9981614 TI - Weak localization coexisting with a magnetic field in a normal-metal superconductor microbridge. PMID- 9981613 TI - Competition between magnetism and superconductivity in TmNi2B2C observed by muon spin rotation. PMID- 9981615 TI - Multilayer pinning in a-axis-oriented EuBa2Cu3O7/PrBa2Cu3O7 superconducting superlattices. PMID- 9981617 TI - Evidence for two vortex phase transitions in Tl2Ba2CaCu2O8 thin films. PMID- 9981616 TI - Mixed-state quasiparticle spectrum for d-wave superconductors. PMID- 9981618 TI - Effect of Zn doping on charge transport in YBa2Cu3O7-y. PMID- 9981620 TI - Conductivity of a metal with inverse-power-law correlated impurities. PMID- 9981619 TI - Variations of electronic states in La2-xSrxCuO4 (x=0 to 0.30) investigated by scanning tunneling spectroscopy. PMID- 9981621 TI - Charge and spin dynamics of the two-dimensional t model in leading order of a 1/N expansion. PMID- 9981622 TI - Two-dimensional t-J model at low electron density. PMID- 9981623 TI - Negative magnetoresistance as a result of hopping conduction in polycrystalline thin films of beta -FeSi2. PMID- 9981624 TI - Exchange interaction in diluted magnetic semiconductors: Crystal-structure induced anisotropy. PMID- 9981625 TI - Acoustic scattering of electrons in degenerate semiconductors at low lattice temperatures. PMID- 9981627 TI - Theoretical study on the high-pressure phase transformation in ZnSe. PMID- 9981626 TI - Direct observation of electron relaxation in intrinsic GaAs using femtosecond pump-probe spectroscopy. PMID- 9981628 TI - Polaron effects on the impurity binding energy in quantum wires. PMID- 9981630 TI - Retarded electromagnetic response of a spherical quantum dot: A self-consistent field calculation. PMID- 9981629 TI - Landau-level populations and slow energy relaxation of a two-dimensional electron gas probed by tunneling spectroscopy. PMID- 9981631 TI - In situ study of Fermi-level pinning on n- and p-type GaAs (001) grown by molecular-beam epitaxy using photoreflectance. PMID- 9981632 TI - Acoustic plasma wave in a quantum-size cylindrical electron-hole plasma. PMID- 9981633 TI - Defect creation in amorphous-silicon thin-film transistors. PMID- 9981634 TI - Effect of polarization screening length on electron-pump cotunneling errors. PMID- 9981635 TI - Observation of persistent spectral hole burning in CuBr quantum dots. PMID- 9981636 TI - Observation of spin-splitting crossing between subbands in the optically detected cyclotron-resonance spectra of In0.53Ga0.47As/In0.52Al0.48As heterojunctions. PMID- 9981638 TI - Interedge tunneling and the fractional quantum Hall effect in double-quantum-well systems. PMID- 9981637 TI - Behavior of In0.48Ga0.52P/(Al0.2Ga0.8)0.52In0.48P quantum-well luminescence as a function of temperature. PMID- 9981639 TI - Transport properties of a Si/SiGe quantum point contact in the presence of impurities. PMID- 9981641 TI - Scanning-tunneling-microscopy and spectroscopy simulation of the GaAs(110) surface. PMID- 9981640 TI - Theory of Shubnikov-de Haas oscillations around the nu =1/2 filling factor of the Landau level: Effect of gauge-field fluctuations. PMID- 9981642 TI - Universal correlations in random matrices and one-dimensional particles with long range interactions in a confinement potential. PMID- 9981643 TI - Weak localization and the transmission matrix. PMID- 9981644 TI - Au/GaAs interface annealing study by positron-lifetime spectroscopy. PMID- 9981645 TI - Hot-phonon effects in femtosecond luminescence spectra of electron-hole plasmas in CdS. PMID- 9981646 TI - Determination of the band offset of CdTe/Cd1-xMnxTe multiple quantum wells with very low x values. PMID- 9981647 TI - Bleaching of excitons in a (Zn,Cd)Se/Zn(S,Se)/(Zn,Mg)(S,Se) laser diode under lasing conditions. PMID- 9981648 TI - Influence of electron-electron scattering on shot noise in diffusive contacts. PMID- 9981649 TI - Electron-electron momentum relaxation in a two-dimensional electron gas. PMID- 9981650 TI - Cu-O atomic chains observed on an ultrathin film of Cu(110). PMID- 9981651 TI - K-induced surface vibrations on Ni(111). PMID- 9981652 TI - Electronic structures and stability of Si60 and C6060 clusters. PMID- 9981653 TI - Dynamical screening in Auger processes near metal surfaces. PMID- 9981655 TI - Local density of states for the strained V-Ta(100) interface. PMID- 9981654 TI - Oxygen diffusion in solid C60: A molecular-dynamics calculation. PMID- 9981656 TI - Freezing and melting of mercury in porous glass. PMID- 9981658 TI - Reflectance of conducting polypyrrole: Observation of the metal-insulator transition driven by disorder. PMID- 9981657 TI - Shape isomerism in sodium clusters with 10 <= Z <= 44: Jellium model with quadrupole, octupole, and hexadecapole deformations. PMID- 9981659 TI - Deducing correlation parameters from optical conductivity in the Bechgaard salts. PMID- 9981660 TI - Nonlocal screening effects on core-level photoemission spectra investigated by large-cluster models. PMID- 9981661 TI - Transport studies in H3PO4-doped polyaniline. PMID- 9981662 TI - Two-dimensional Hubbard-Holstein model. PMID- 9981663 TI - Resonant photoemission spectra at the 4f and 5p levels of Tm across the 4d-4f absorption threshold. PMID- 9981664 TI - Plasmon lifetime, zone-boundary collective states, and energy-loss spectra of lithium. PMID- 9981665 TI - General separability of linear and nonlinear optical susceptibilities. PMID- 9981666 TI - Geometrical approach to bosonization of D>1 dimensional (non)-Fermi liquids. PMID- 9981667 TI - Correlation effects in ionic crystals: The cohesive energy of MgO. PMID- 9981668 TI - Excitons, biexcitons, and the band gap in poly(p-phenylene vinylene). PMID- 9981669 TI - Self-oscillations at photoinduced impurity breakdown in GaAs. PMID- 9981670 TI - Relation between the metastability of EL2 and the photosensitivity of local vibrational modes in semi-insulating GaAs. PMID- 9981671 TI - Microscopic structure of the DX center in Si-doped AlxGa1-xAs: Observation of a vacancy by positron-annihilation spectroscopy. PMID- 9981672 TI - Reaction kinetics of hydrogen-gold complexes in silicon. PMID- 9981673 TI - First-principles calculation of Ga-based semiconductors. PMID- 9981674 TI - Occupied electronic states of CaSi2 and CaSi: Soft-x-ray-fluorescence spectroscopy. PMID- 9981676 TI - Electronic transport in lightly doped CoSb3. PMID- 9981675 TI - Size, shape, and composition of luminescent species in oxidized Si nanocrystals and H-passivated porous Si. PMID- 9981677 TI - Field-induced exciton breaking in conjugated polymers. PMID- 9981678 TI - Spatiotemporal dynamics of photon echoes from continuum states in semiconductors. PMID- 9981679 TI - Ab initio investigation of the dislocation structure and activation energy for dislocation motion in silicon carbide. PMID- 9981680 TI - Strain splitting of nitrogen acceptor levels in ZnSe. PMID- 9981681 TI - Structural and optoelectronic properties of indium-doped a-Ge:H thin films. PMID- 9981682 TI - Properties of gallium-doped hydrogenated amorphous germanium. PMID- 9981683 TI - Ab initio calculations of two-photon absorption spectra in semiconductors. PMID- 9981685 TI - Aggregate defects of gold and platinum with lithium in silicon: II. Electronic structure calculations. PMID- 9981684 TI - Aggregate defects of gold and platinum with lithium in silicon: I. Magnetic resonance investigations. PMID- 9981686 TI - Damped plasma waves in photoexcited plasma in semiconductors. PMID- 9981687 TI - Second-sound wave in photoinjected plasma in semiconductors. PMID- 9981688 TI - Conditions for conductance quantization in realistic models of atomic-scale metallic contacts. PMID- 9981689 TI - Boundaries and junctions in two parity-violating models in 2+1 dimensions. PMID- 9981690 TI - Laser processes and optical nonlinearities in ZnSe heterostructures. PMID- 9981691 TI - Theoretical study of band-edge states in Sn1Gen strained-layer superlattices. PMID- 9981693 TI - Intrinsic high-frequency characteristics of tunneling heterostructure devices. PMID- 9981692 TI - Flicker noise induced by dynamic impurities in a quantum point contact. PMID- 9981694 TI - Bloch oscillations and other dynamical phenomena of electrons in semiconductor superlattices. PMID- 9981696 TI - Dynamics of exciton diffusion in SiGe quantum wells on a ssV-groove patterned Si substrate. PMID- 9981695 TI - Tight-binding study of ZnSe/ZnTe strained superlattices: Determination of the band offset from the optical properties. PMID- 9981697 TI - Real-time spectroscopic ellipsometry study of the growth of amorphous and microcrystalline silicon thin films prepared by alternating silicon deposition and hydrogen plasma treatment. PMID- 9981698 TI - Directional coupling in dual-branch electron-waveguide junctions. PMID- 9981699 TI - Diffuse scattering in partially ordered III-V semiconductor alloys. PMID- 9981700 TI - Anomalous diffusion in a high magnetic field and the quasiparticle density of states. PMID- 9981701 TI - Heteroepitaxial diamond films on silicon (001): Interface structure and crystallographic relations between film and substrate. PMID- 9981702 TI - Tilting in the arsenic-induced c(4 x 4) reconstruction of the GaAs{001} surface. PMID- 9981703 TI - Aligned carbon-hydrogen complexes in GaAs formed by the decomposition of trimethylgallium during low-pressure metal-organic vapor-phase epitaxy. PMID- 9981705 TI - Current characteristics of the double-barrier Al0.25Ga0.75As/Al0.45Ga0.55As/GaAs single-quantum-well structures. PMID- 9981704 TI - Ultrafast relaxation of photoexcited carriers in semiconductor quantum wires: A Monte Carlo approach. PMID- 9981707 TI - Effect of spin degeneracy on scaling in the quantum Hall regime. PMID- 9981706 TI - Quasi-three-dimensional Green's-function simulation of coupled electron waveguides. PMID- 9981708 TI - Weak localization effects on spin relaxation of excitons in quantum wells. PMID- 9981710 TI - Effects of epitaxial strain and ordering direction on the electronic properties of GaSb/InSb and InAs/InSb superlattices. PMID- 9981709 TI - Dynamics of an atomic switch computed by first-principles molecular dynamics. PMID- 9981711 TI - Thermoelectric properties of a series of Landauer barriers. PMID- 9981713 TI - Magneto-optical studies of the type-I/type-II crossover and band offset in ZnTe/Zn1-xMnxTe superlattices in magnetic fields up to 45 T. PMID- 9981712 TI - Nonlinear optical study of the Si(111)7 x 7 to 1 x 1 phase transition: Superheating and the nature of the 1 x 1 phase. PMID- 9981714 TI - Spontaneous Aharonov-Casher effect of neutral hard-core bosons in one-dimensional mesoscopic rings. PMID- 9981715 TI - Resonant acoustic-phonon modes in a quantum wire. PMID- 9981716 TI - Theory of hopping magnetoresistance induced by Zeeman splitting. PMID- 9981717 TI - Electronic structure of intercalated graphite studied by soft-x-ray-emission spectroscopy. PMID- 9981718 TI - Load dependence of two-dimensional atomic-scale friction. PMID- 9981720 TI - Polygonal spiral of coil-shaped carbon nanotubules. PMID- 9981719 TI - Electric-current transmission through the contact of two metals. PMID- 9981721 TI - Theory of the contribution to sliding friction from electronic excitations in the microbalance experiment. PMID- 9981723 TI - Oriented N2 molecules intercalated in C24Rb. PMID- 9981722 TI - Molecular-dynamics simulations of nickel oxide surfaces. PMID- 9981724 TI - Resistance of atomic wires. PMID- 9981725 TI - Chemisorption of Li on jellium: Local density of states and nuclear-spin relaxation. PMID- 9981726 TI - Annihilation of positrons trapped at the alkali-metal-covered transition-metal surface. PMID- 9981727 TI - Diffusion of Cu on Cu surfaces. PMID- 9981728 TI - Ab initio study of the surface and interfacial properties of a layered MgO/NiO film. PMID- 9981729 TI - Low-energy-electron stimulated desorption of metastable particles from condensed N2 and CO. PMID- 9981731 TI - Monte Carlo study of temperature-programmed desorption spectra with attractive lateral interactions. PMID- 9981730 TI - Phase transitions in bcc(110) binary-alloy thin films. PMID- 9981733 TI - Diffuse scattering and orientational correlations in solid C60. PMID- 9981732 TI - Asymptotic shape of elastic networks. PMID- 9981734 TI - Dimer-row pattern formation in diamond (100) growth. PMID- 9981736 TI - Erratum: Femtosecond hole relaxation in n-type modulation-doped quantum wells PMID- 9981735 TI - Smoothing of rough surfaces. PMID- 9981737 TI - CriticalbehavioroftheT=0 2kF density-wave phase transition in a two-dimensional Fermi liquid. PMID- 9981738 TI - Electronic-structure calculations based on the finite-element method. PMID- 9981739 TI - Transverse-electric polarized nonlinear guided polaritons in films with a steplike dielectric function. PMID- 9981740 TI - de Haas-van Alphen study of the charge-transfer salt alpha -(BEDT-TTF)2KHg(SCN)4 in pulsed magnetic fields of up to 54 T. PMID- 9981741 TI - Temperature dependence of electronic states in (TaSe4)2I. PMID- 9981742 TI - Electric-field activated variable-range hopping transport in PrBa2Cu3O7- delta. PMID- 9981743 TI - Fluctuation effects in quasi-one-dimensional conductors: Optical probing of thermal lattice fluctuations. PMID- 9981745 TI - Drude weight and dc conductivity of correlated electrons. PMID- 9981744 TI - Heavy-fermion semiconductor behavior of the SU(Nd) Anderson lattice model. PMID- 9981746 TI - Hot-electron relaxation: An exactly solvable model and improved quantum kinetic equations. PMID- 9981747 TI - Effects of quantum lattice fluctuations on the charge-density wave of halogen bridged mixed-valence transition-metal linear complexes. PMID- 9981749 TI - Dielectric susceptibility measurements of the primary and secondary relaxation in polybutadiene. PMID- 9981748 TI - Fluctuation effects on the electrodynamics of quasi-one-dimensional conductors above the charge-density-wave transition. PMID- 9981750 TI - Energy and momentum conservation during energetic-carrier generation and recombination in silicon. PMID- 9981751 TI - Nuclear-spin echoes in GaAs:Zn and GaAs:In. PMID- 9981752 TI - Observation of Fano resonance in heavily doped p-type silicon at room temperature. PMID- 9981753 TI - Tight-binding molecular-dynamics study of point defects in GaAs. PMID- 9981754 TI - Computer model of tetrahedral amorphous diamond. PMID- 9981755 TI - Positron effective mass in silicon. PMID- 9981757 TI - Monte Carlo simulation of electron drift velocity in low-temperature-grown gallium arsenide in a Schottky-barrier model. PMID- 9981756 TI - High-field electron-drift measurements and the mobility edge in hydrogenated amorphous silicon. PMID- 9981758 TI - Cryogenic cooling using tunneling structures with sharp energy features. PMID- 9981760 TI - Phonon scattering of two-dimensional electrons in a strong magnetic field. PMID- 9981759 TI - Initial stage of Ag growth on Si(001) studied by high-resolution Rutherford backscattering spectroscopy. PMID- 9981761 TI - Phonons and radiative recombination in self-assembled quantum dots. PMID- 9981762 TI - Confined excitons in semiconductors: Correlation between binding energy and spectral absorption shape. PMID- 9981763 TI - Imaging of edge channels in the integer quantum Hall regime by the lateral photoelectric effect. PMID- 9981764 TI - Temperature dependence of electron focusing in In1-xGaxAs/InP heterojunctions. PMID- 9981765 TI - Double 2s-1s resonance in LO-phonon-assisted secondary emission of quantum-well structures. PMID- 9981766 TI - Electron transmission through a single nonabrupt GaAs/AlxGa1-xAs barrier subjected to an electric field. PMID- 9981767 TI - Energy distribution of interface states in the band gap of GaAs determined from x ray photoelectron spectra under biases. PMID- 9981769 TI - Core-level shifts on clean and adsorbate-covered Si(113) surfaces. PMID- 9981768 TI - Folded phonons from lateral periodicity in (311) GaAs/AlAs corrugated superlattices. PMID- 9981771 TI - Scanning-tunneling-microscopy and photoemission study of an alkali-metal-induced structural phase transition: Si(111)-(7 x 7) into Si(111)-Na(3 x 1). PMID- 9981770 TI - Electron transport through one-dimensional lateral surface superlattices in magnetic fields. PMID- 9981772 TI - Ge overlayers on Si(001) studied by surface-extended x-ray-absorption fine structure. PMID- 9981773 TI - Transmitted-acoustic-phonon drag between two-dimensional electron gases in GaAs/AlxGa1-xAs systems at low temperatures: Monte Carlo study. PMID- 9981774 TI - Phosphine adsorption and decomposition on Si(100) 2 x 1 studied by STM. PMID- 9981775 TI - Ab initio molecular-dynamics study of the stability and optical properties of ultrasmall III-V hydrogenated clusters. PMID- 9981776 TI - Electron localization in a two-dimensional system with random magnetic flux. PMID- 9981777 TI - Variational quantum Monte Carlo study of two-dimensional Wigner crystals: Exchange, correlation, and magnetic-field effects. PMID- 9981779 TI - Singularities in the Fermi-liquid description of a partially filled Landau level and the energy gaps of fractional quantum Hall states. PMID- 9981778 TI - Binding and diffusion of hydroxyl radicals on Si(100): A first-principles study. PMID- 9981780 TI - Photoluminescence of the electron-dressed confined X- exciton in an n-type AlAs/GaAs resonant tunneling device. PMID- 9981781 TI - Quantum-confined Stark effects in semiconductor quantum dots. PMID- 9981782 TI - Coupling between electrons and acoustic phonons in semiconductor nanostructures. PMID- 9981783 TI - Spatial-confinement effect on phonons and excitons in PbI2 microcrystallites. PMID- 9981785 TI - Laser chemical-vapor deposition of titanium nitride. PMID- 9981784 TI - Path-length distribution of photoelectrons emitted from homogeneous noncrystalline solids: Consequences for inelastic-background analysis. PMID- 9981787 TI - Magnetic hyperfine field on 111Cd in metastable bcc cobalt. PMID- 9981786 TI - Epitaxial growth of bismuth films and bismuth-antimony heterostructures. PMID- 9981788 TI - Growth of C60 thin films on GeS(001) studied by scanning force microscopy. PMID- 9981789 TI - Surface diffusion and continuous phase transitions in adsorbed overlayers. PMID- 9981790 TI - Interaction of atomic hydrogen with the diamond C(111) surface studied by infrared-visible sum-frequency-generation spectroscopy. PMID- 9981791 TI - Analysis of the T1u PMID- 9981793 TI - Electronic states of the cap structure in the carbon nanotube. PMID- 9981792 TI - Mechanistic study of atomic desorption resulting from the keV-ion bombardment of fcc{001} single-crystal metals. PMID- 9981794 TI - Enhanced scattering from a planar waveguide structure with a slightly rough boundary. PMID- 9981795 TI - Electronically driven adsorbate excitation mechanism in femtosecond-pulse laser desorption. PMID- 9981796 TI - Mercury surface-plasmon dispersion: Experiment and theory. PMID- 9981797 TI - Copper adsorption potentials of MgO(001). PMID- 9981798 TI - Pairing in C60: A Gutzwiller approach. PMID- 9981799 TI - Classical and quantum size effects in electron conductivity of films with rough boundaries. PMID- 9981800 TI - Structural and electronic properties of Li- and Cu-doped beta -rhombohedral boron constructed from icosahedral and truncated icosahedral clusters. PMID- 9981802 TI - Comment on "Relation between copper L x-ray fluorescence and 2p x-ray photoelectron spectroscopies" PMID- 9981801 TI - Theory of exciton spectra of incompressible quantum liquids. PMID- 9981803 TI - Reply to "Comment on 'Relation between copper L x-ray fluorescence and 2p x-ray photoelectron spectroscopies' " PMID- 9981805 TI - Pressure-induced insulator-metal transitions in the spinless Falicov-Kimball model. PMID- 9981804 TI - Density-functional molecular dynamics with real-space finite difference. PMID- 9981807 TI - Large-scale electronic-structure calculations with multigrid acceleration. PMID- 9981806 TI - Density-functional theory and strong interactions: Orbital ordering in Mott Hubbard insulators. PMID- 9981808 TI - Density-matrix renormalization-group calculation of correlation functions in the one-dimensional Hubbard model. PMID- 9981809 TI - Reentrant insulator-metal transition in the half-filled Hubbard model. PMID- 9981810 TI - Phase slip and the spatiotemporal response of charge-density waves in NbSe3. PMID- 9981811 TI - First-principles calculation of the electronic structure of condensed spin polarized excited triplet-state helium. PMID- 9981812 TI - Excitons in a II-VI semiconductor microcavity in the strong-coupling regime. PMID- 9981813 TI - Intrinsic bistability by charge accumulation in an L-valley state in GaSb-AlSb resonant-tunneling diodes. PMID- 9981814 TI - Coulomb-gas approach to quantum motion in random magnetic fields. PMID- 9981815 TI - Crossover between different regimes of current distribution in the quantum Hall effect. PMID- 9981816 TI - Universal dissipative resistivity in the fractional quantum Hall effect of two dimensional hole systems. PMID- 9981817 TI - Layer-depopulation- and magnetic-field-induced resistance oscillations in a triple-layer electron system. PMID- 9981819 TI - Magnitude and sign of the carrier-magnetic-ion exchange-interaction term in the monolayer regions next to the interface between a magnetic and nonmagnetic semiconductor. PMID- 9981818 TI - High-resolution structural study of Bi on Si(001). PMID- 9981820 TI - Magneto-optical spectroscopy of positively charged excitons in GaAs quantum wells. PMID- 9981821 TI - Interband second-harmonic generation in Zn1-xCdxSe/ZnSe strained quantum wells. PMID- 9981823 TI - Edge of the two-dimensional electron gas in a gated heterostructure. PMID- 9981822 TI - Diamagnetic shift as a measure of the penetration of a quasi-two-dimensional exciton into quantum-well barriers. PMID- 9981824 TI - Landauer conductance of Luttinger liquids with leads. PMID- 9981825 TI - Hybrid excitons in parallel organic and inorganic semiconducting quantum wires. PMID- 9981826 TI - C60 on Al(111): Covalent bonding and surface reconstruction. PMID- 9981827 TI - Investigation of the absorption edge of C60 fullerite. PMID- 9981829 TI - Band-gap closure of Ar(H2)2 under pressure. PMID- 9981828 TI - Temperature dependence of surface phonons of Al(110). PMID- 9981831 TI - Ion-velocity-dependent track formation in yttrium iron garnet: A thermal-spike analysis. PMID- 9981830 TI - Paramagnetic electron traps in reduced stabilized zirconia. PMID- 9981832 TI - Evolution of a ferroelastic domain structure in an incommensurate phase of barium sodium niobate (Ba2NaNb5O15). PMID- 9981833 TI - Radial distribution function of a new form of amorphous diamond shock induced from C60 fullerene. PMID- 9981834 TI - Homogeneous line broadening in long-lived nuclear states. PMID- 9981835 TI - Kink dynamics in the highly discrete and coupled sine-Gordon system. PMID- 9981836 TI - Spin-dependent surface transmission in 3d metals: Implications for magnetic dichroism measurements of the valence bands. PMID- 9981837 TI - Lattice model for exchange-coupled ferromagnetic multilayer systems. PMID- 9981838 TI - Pseudo-marginal-Fermi-liquid behavior in antiferromagnetic metals. PMID- 9981839 TI - Extended high-temperature series for the N-vector spin models on three dimensional bipartite lattices. PMID- 9981840 TI - Weak-coupling approach to hole-doped S=1 Haldane systems. PMID- 9981841 TI - Electronic structure and enhancement of magnetic moments in the ferromagnetic nitride Fe16N2. PMID- 9981842 TI - Superconductivity of ZrRuSi prepared at high pressure. PMID- 9981843 TI - Thermodynamics and response of a spin-charge-separated superconductor. PMID- 9981844 TI - Effect of superconducting correlation on the localization of quasiparticles in low dimensions. PMID- 9981845 TI - Light scattering from electronic excitations in YNi2B2C. PMID- 9981846 TI - Vortex dynamics below the flux-lattice melting transition in YBa2Cu3O7- delta. PMID- 9981847 TI - Anomalous magnetic behavior in Bi2Sr2CaCu2O8+y single crystals near the superconducting-transition regime. PMID- 9981848 TI - Evidence of redistribution of the itinerant holes below Tc in Ba2Sr2CaCu2O8 superconductors: A polarized x-ray-absorption study. PMID- 9981849 TI - Superconductivity from correlated hopping. PMID- 9981850 TI - Long-range Coulomb repulsion and finite-size approximations. PMID- 9981851 TI - Phase diagrams of bcc alloys at low temperatures with ballistic atom movements. PMID- 9981852 TI - Quasielastic neutron scattering from anharmonic oscillators subject to weak frictional forces. PMID- 9981853 TI - Stresses in strained GeSi stripes: Calculation and determination from Raman measurements. PMID- 9981854 TI - Electron correlation in the self-trapped hole and exciton in the NaCl crystal. PMID- 9981855 TI - Dynamics of a photoinduced phase transition in polydiacetylene crystals. PMID- 9981856 TI - Severe creep of a crystalline metallic layer induced by swift-heavy-ion irradiation. PMID- 9981857 TI - Lattice location of Pr3+ ions in LiNbO3. PMID- 9981858 TI - Quadrupolar phases in UPd3. PMID- 9981859 TI - Ab initio Hartree-Fock study of structural and electronic properties of beta Si3N4 and beta -C3N4 compounds. PMID- 9981860 TI - First-principles theory of ferroelectric phase transitions for perovskites: The case of BaTiO3. PMID- 9981862 TI - Landau theory of a constrained ferroelastic in two dimensions. PMID- 9981861 TI - Vacancies and impurities in aluminum and magnesium. PMID- 9981864 TI - X-ray absorption at the Ca K edge in natural-garnet solid solutions: A full multiple-scattering investigation. PMID- 9981863 TI - X-ray-absorption fine-structure standards: A comparison of experiment and theory. PMID- 9981866 TI - Ergodic-nonergodic glass transition and enthalpy relaxation of a supercooled liquid PMID- 9981865 TI - Reconciling ionic-transport properties with atomic structure in oxide glasses. PMID- 9981867 TI - Phason elasticity of a three-dimensional quasicrystal: A transfer-matrix method. PMID- 9981868 TI - Microscopic theory of chain pullout in polymeric liquid crystals. PMID- 9981869 TI - Structural free volumes and systematics of positron lifetimes in quasicrystalline decagonal and adjacent crystalline phases of Al-Ni-Co, Al-Cu-Co, and Al-Ni-Fe alloys. PMID- 9981870 TI - Quantum diffusion and localization of positive muons in superconducting aluminum. PMID- 9981872 TI - Homogeneous and inhomogeneous linewidths of Eu3+ in disordered crystalline systems. PMID- 9981871 TI - Internal oscillations of solitons in (CH3)4NMnCl3 above and below TN. PMID- 9981874 TI - Stability of metastable structures in dissipative ac dynamics of the Frenkel Kontorova model. PMID- 9981873 TI - Infrared absorption in oxides in the presence of both large and small polarons. PMID- 9981875 TI - Dynamical symmetry of chaotic systems. PMID- 9981877 TI - Perpendicular magnetic anisotropy and temperature-dependent reorientation transition of the magnetization in CeH2/Fe multilayers. PMID- 9981876 TI - Spin diffusion on a lattice: Classical simulations and spin coherent states. PMID- 9981878 TI - Quenching of orbital momentum by crystalline fields in a multichannel Kondo impurity. PMID- 9981880 TI - Spin relaxation effects in the perpendicular magnetoresistance of magnetic multilayers. PMID- 9981879 TI - Correlation between the interface structure and magnetic and transport properties for Co/Cu(110) and Ni8Fe2/Cu/Co/Cu(110) superlattices. PMID- 9981881 TI - Itinerant electrons in strong magnetic fields: Onset of a metamagnetic transition. PMID- 9981882 TI - Comparison of branching ratio and sum-rule analyses of magnetic circular dichroism in x-ray-absorption spectroscopy. PMID- 9981883 TI - 57Fe Mossbauer investigations on the Dy0.73Tb0.27Fe2-xNix and Ho0.85Tb0.15Fe2 yNiy systems. PMID- 9981885 TI - Aharonov-Casher effect in the Heisenberg spin chain with many impurities. PMID- 9981884 TI - Response of Ising systems to oscillating and pulsed fields: Hysteresis, ac, and pulse susceptibility. PMID- 9981886 TI - Observation of x-ray magnetic scattering in Nd2CuO4. PMID- 9981887 TI - Density-matrix renormalization-group studies of the spin-1/2 Heisenberg system with dimerization and frustration. PMID- 9981888 TI - Magnetic-field effect on sound propagation as a probe of electronic structure and electron interaction in an itinerant-electron ferromagnet. PMID- 9981889 TI - Strong changes in the magnetic properties of ultrathin Co/Cu(001) films due to submonolayer quantities of a nonmagnetic overlayer. PMID- 9981890 TI - Magnetic properties of quantum Heisenberg ferromagnets with long-range interactions. PMID- 9981891 TI - Simple formulation of the two-channel Kondo model. PMID- 9981892 TI - Four-coloring model on the square lattice: A critical ground state. PMID- 9981893 TI - Electron scattering at interfaces: A tight-binding approach. PMID- 9981895 TI - Interaction of two localized spins in an itinerant ferromagnetic medium. PMID- 9981894 TI - J1-J2 quantum Heisenberg antiferromagnet on the triangular lattice: A group symmetry analysis of order by disorder. PMID- 9981896 TI - Critical behavior of the three-dimensional random-field Ising model: Two-exponent scaling and discontinuous transition. PMID- 9981897 TI - Longitudinal spin relaxation in simple stochastic models for disordered systems. PMID- 9981898 TI - Lifting of multiphase degeneracy by quantum fluctuations. PMID- 9981899 TI - Phase transitions in the uniformly frustrated XY model with frustration parameter f=1/3 studied with use of the microcanonical Monte Carlo technique. PMID- 9981900 TI - Topological solitons and geometrical frustration. PMID- 9981901 TI - Frustrated spin-Peierls chains. PMID- 9981902 TI - Subsurface correlations in the d-wave Josephson junction. PMID- 9981903 TI - Observation of granularity in YNi2B2C superconductors containing normal impurity phases. PMID- 9981905 TI - Time-dependent functional theory for superconductors. PMID- 9981904 TI - Extraordinary sensitivity of the internal Doppler effect in a superfluid 4He-3He admixture. PMID- 9981906 TI - Analytical results for giant Shapiro steps in Josephson arrays. PMID- 9981907 TI - Magnetism and superconductivity in RPtSi (R=La, Ce, Nd, and Sm). PMID- 9981908 TI - Spin and charge modes of the t-J ladder. PMID- 9981909 TI - Andreev scattering in the anisotropic heavy-fermion superconductor UPt3. PMID- 9981910 TI - Statistical quasiparticles in transverse dynamics of gases. PMID- 9981911 TI - Evidence for two-particle normal-state tunneling in Ba1-xKxBiO3 native-barrier tunnel junctions. PMID- 9981913 TI - Oxygen isotope effect on the effective mass of carriers from magnetic measurements on La2-xSrxCuO4. PMID- 9981912 TI - Temperature-dependent x-ray diffuse scattering from single crystals of La2 xSrxCuO4. PMID- 9981914 TI - Epitaxial growth and critical currents in (013)/(103)- and (110)-oriented YBa2Cu3Ox films. PMID- 9981915 TI - Pressure effect on the Tc of HgBa2CuO4+ delta with 0.07 <= delta <= 0.39. PMID- 9981916 TI - Thermally activated flux motion in a-axis YBa2Cu3O7/PrBa2Cu3O7 superlattices. PMID- 9981917 TI - Thermodynamic and electromagnetic properties of hard-core charged bosons on a lattice. PMID- 9981919 TI - Critical Josephson current in a model Pb/YBa2Cu3O7- delta junction. PMID- 9981918 TI - Charge fluctuations in the four-band extended Hubbard model. PMID- 9981920 TI - Charge dynamics in the planar t-J model. PMID- 9981922 TI - Electronic structure and Fermi surface of the two-dimensional three-band Hubbard model in doped cuprates. PMID- 9981921 TI - Correlation of flux lines in single-crystal Bi2Sr2CaCu2O8 with columnar defects. PMID- 9981923 TI - Erratum: Nonlinear travelling waves in ferroelectrics PMID- 9981924 TI - Erratum: Electron-phonon coupling and d-wave superconductivity in the cuprates PMID- 9981925 TI - Total-energy study of hydrogen ordering in PdHx (0 <~ x <~ 1). PMID- 9981926 TI - Photoactivation of hole centers in cubic stabilized zirconia. PMID- 9981927 TI - Direct observation of rough-smooth twin structure in silver halides by high resolution electron microscopy. PMID- 9981928 TI - Pressure-induced critical behavior of KMnF3 close to Pc=3.1 GPa: X-ray diffraction results. PMID- 9981929 TI - Volume-expansion-induced lattice instability and solid-state amorphization. PMID- 9981930 TI - Crossover exponents in percolating superconductor-nonlinear-conductor mixtures. PMID- 9981931 TI - First-principles calculations of the vibrational properties of H centers in KCl crystals. PMID- 9981932 TI - Low-temperature magnetic phase of UCu2Ge2: A macroscopic, mesoscopic, and microscopic study. PMID- 9981934 TI - Stability of the insulating phase in the chiral Kondo-lattice model. PMID- 9981933 TI - Enhanced magnetic anisotropy energy density for superparamagnetic particles of cobalt. PMID- 9981935 TI - Scaling field of the anisotropic XY model in one dimension. PMID- 9981936 TI - Impurity energy level in the Haldane gap. PMID- 9981937 TI - Magnetic consequences of NO chemisorption on (100) metal surfaces. PMID- 9981939 TI - Equivalence of the antiferromagnetic Heisenberg ladder to a single S=1 chain. PMID- 9981938 TI - High-energy paramagnetic spectral response of CeNi2. PMID- 9981941 TI - Continuous Josephson media and vortices. PMID- 9981940 TI - Near constancy of the pressure dependence of Tc across families of organic and fullerene superconductors. PMID- 9981942 TI - Cylindrical Korteweg-de Vries solitons in the vortex dynamics of an ultraclean type-II superconductor. PMID- 9981944 TI - Disorder and superconductivity in Mo/Si multilayers. PMID- 9981943 TI - Resonant macroscopic quantum tunneling in small Josephson junctions: Effect of temperature. PMID- 9981945 TI - Stability of multicharged vortices in a model of superflow. PMID- 9981946 TI - Influence of the critical current distribution on the remanent magnetization in thin YBa2Cu3O7 films. PMID- 9981947 TI - Magnetization jump and the vortex-lattice melting transition in YBa2Cu3Oy. PMID- 9981948 TI - Overdoped regime of the high-Tc superconductor HgBa2CuO4+ delta and the relation between normal and superconducting carrier densities. PMID- 9981949 TI - Intrinsic high-Tc Josephson junctions in random-telegraph-noise fluctuators. PMID- 9981950 TI - Anisotropic pressure dependence of the resistivity in YBa2Cu4O8. PMID- 9981951 TI - Specific-heat critical behavior of the structural random-field system Dy(AsxV1 x)O4. PMID- 9981953 TI - Pressure-induced phase transition of quartz-type GaPO4. PMID- 9981952 TI - Metastable structures of solid hydrogen. PMID- 9981955 TI - O- holes associated with alkali acceptors in BaTiO3. PMID- 9981954 TI - High-pressure Brillouin scattering and elastic properties of liquid and solid methane. PMID- 9981956 TI - Roughening and preroughening in the six-vertex model with an extended range of interaction. PMID- 9981957 TI - Polarization of a semi-infinite crystal by a point defect at the surface. PMID- 9981958 TI - Equilibrium phase transitions in a porous medium. PMID- 9981959 TI - Theoretical study of lithium intercalation in rutile and anatase. PMID- 9981961 TI - Stability and phonons of KTaO3. PMID- 9981960 TI - Electron emission from 57Fe nuclei excited with synchrotron radiation. PMID- 9981962 TI - Conductivity in quasicrystals via hierarchically variable-range hopping. PMID- 9981963 TI - Simulation of radiation-induced structural transformation in amorphous metals. PMID- 9981964 TI - Central-force model with the next-nearest-neighbor interaction: A series approach. PMID- 9981965 TI - Structure and bonding in liquid tellurium. PMID- 9981966 TI - Role of phason defects on the conductance of a one-dimensional quasicrystal. PMID- 9981967 TI - Experimental evidence of the formation of a reentrant spin-glass phase in alloying two ferromagnetic CoPt3 and MnPt3 compounds. PMID- 9981968 TI - Local magnetic properties of PrBa2Cu3O6+x: NMR and NQR in crystals. PMID- 9981969 TI - Low-temperature thermodynamic study of the XY model using a self-consistent harmonic approximation. PMID- 9981970 TI - Real-space renormalization-group study of the phase diagram of two coupled quantum spin-1/2 chains. PMID- 9981971 TI - Properties of lightly doped t-J two-leg ladders. PMID- 9981972 TI - Influence of vanadium on spin- and charge-density waves in chromium. PMID- 9981973 TI - Role of bound states of magnetic layers in the theory of multilayer interaction. PMID- 9981975 TI - Doping an optimized resonance-valence-bond state: A picture of spin-charge separation. PMID- 9981974 TI - NMR study of the ferromagnetic phases of SmMn2Ge2 as a function of temperature and pressure. PMID- 9981976 TI - Calculated magneto-optical Kerr effect in Fe, Co, and Ni. PMID- 9981977 TI - Coherent aspects of the local dipolar field in echo dynamics: A spectral narrowing effect. PMID- 9981978 TI - Anisotropic magnetic properties of TbNi2B2C single crystals. PMID- 9981980 TI - Continuum-field description of one-dimensional dimerized spin-1/2 Heisenberg antiferromagnets. PMID- 9981979 TI - Magneto-optical properties of MnBi and MnBiAl. PMID- 9981981 TI - Impurity scattering of spin waves in a doped Mott-Hubbard antiferromagnet. PMID- 9981982 TI - Generalized t-t'-J model: Parameters and single-particle spectrum for electrons and holes in copper oxides. PMID- 9981983 TI - Magnetic ordering in the three-dimensional site-disordered Heisenberg model. PMID- 9981984 TI - Muon-spin-relaxation study of the critical longitudinal spin dynamics in a dipolar Heisenberg ferromagnet. PMID- 9981985 TI - Quantum nucleation of magnetic bubbles. PMID- 9981986 TI - Magnetic pair breaking in disordered superconducting films. PMID- 9981987 TI - Quasiparticle current in ballistic constrictions with finite transparencies of interfaces. PMID- 9981988 TI - Surface superconductivity and Hc3 in UPt3. PMID- 9981989 TI - Specific heat of an anisotropic superconductor: Nb3X4 with X=S, Se, and Te. PMID- 9981990 TI - Vortices in stratified superconductors: Application to magnetic force microscopy. PMID- 9981991 TI - Motion of holes on the triangular lattice studied using the t-J model. PMID- 9981992 TI - Decoupling excitations in the far-infrared spectra of a c-axis YBa2Cu3O7- delta single crystal. PMID- 9981993 TI - Theory of the spin gap in high-temperature superconductors. PMID- 9981994 TI - Effect of an electric field on oxygen ordering and superconducting temperature of YBa2Cu3O6+x thin films. PMID- 9981995 TI - d-wave superconductivity in a strongly correlated electron-phonon system. PMID- 9981996 TI - Instability of a tilted vortex line in magnetically coupled layered superconductors. PMID- 9981998 TI - Dynamics of two-dimensional pancake vortices in layered superconductors. PMID- 9981997 TI - Many-body correlation corrections to superconducting pairing in two dimensions. PMID- 9981999 TI - Erratum: Microwave dielectric studies of the spin-density-wave state in (TMTSF)2PF6 PMID- 9982000 TI - Erratum: Thermoelectric power and resistivity of La1.8Sr0.2CaCu2O6- delta and the effects of O2 hot-isostatic-press annealing PMID- 9982001 TI - Erratum: Theoretical study on quantum effects in triangular antiferromagnets with axial anisotropy using the numerically constructed Bogoliubov transformation for magnons PMID- 9982003 TI - X-ray scattering and x-ray fluorescence from materials with rough interfaces. PMID- 9982002 TI - Thermal and vibrational investigation of crystal nucleation and growth from a physically confined and supercooled liquid. PMID- 9982004 TI - Spectroscopic properties and upconversion mechanisms in Er3+-doped fluoroindate glasses. PMID- 9982006 TI - Electric field dependence of pocket and nonpocket impurity gap modes in KI and the establishment of Ag+ quadrupolar deformability. PMID- 9982005 TI - Pressure dependence of static and dynamic ionicity of SiC polytypes. PMID- 9982007 TI - 1H NMR study of proton motions in thallium-deficient TlH2PO4. PMID- 9982009 TI - Anharmonic interatomic potentials of diatomic and linear triatomic molecules studied by extended x-ray-absorption fine structure. PMID- 9982008 TI - High-pressure elastic properties of the VI and VII phase of ice in dense H2O and D2O. PMID- 9982010 TI - Analysis of magnetic-resonance signals from mixed lattices with application to the AsO44- center in the Rb1-x(NH4)xH2PO4 proton glass. PMID- 9982011 TI - Spatially resolved optical studies of F-center diffusion in KBr crystals. PMID- 9982012 TI - First-principles calculation of the pressure dependence of phase equilibria in the Al-Li system. PMID- 9982013 TI - Spatial and temporal scaling of oxide cluster aggregation on a liquid-gallium surface. PMID- 9982014 TI - Coherent forward-scattering amplitude in transmission and grazing incidence Mossbauer spectroscopy. PMID- 9982015 TI - Model interatomic potential for simulations in selenium. PMID- 9982016 TI - Multiple-edge EXAFS refinement: Short-range structure in liquid and crystalline Sn. PMID- 9982017 TI - Effect of host glass on the optical absorption properties of Nd3+, Sm3+, and Dy3+ in lead borate glasses. PMID- 9982018 TI - Hyperfine interactions at europium sites in oxide glasses. PMID- 9982019 TI - Ab initio analysis of structural stability in the compound Ni3V. PMID- 9982021 TI - Molecular dynamics on a realistic model for a strong glass. PMID- 9982020 TI - Critical concentration in percolating systems containing a high-aspect-ratio filler. PMID- 9982023 TI - Resistivity minima in concentrated gamma -Cu100-xMnx alloys (36 <~ x <~ 83). PMID- 9982022 TI - Optical investigation of Eu3+ in a sodium borosilicate glass: Evidence for two different site distributions. PMID- 9982024 TI - Coulomb interactions in two-dimensional lattice structures. PMID- 9982025 TI - Particle-size effect on the percolation and conductivity of dispersed ionic conductors: A random sequential packing model. PMID- 9982026 TI - Phase-field model for activated reaction fronts. PMID- 9982028 TI - Formation of dislocation patterns: Computer simulations. PMID- 9982027 TI - Lattice dynamics of skutterudites: First-principles and model calculations for CoSb3. PMID- 9982029 TI - Accuracy of Davydov's |D1> approximation for soliton dynamics in proteins. PMID- 9982030 TI - Electromagnetic properties of composites containing elongated conducting inclusions. PMID- 9982031 TI - Low-frequency elastic properties of the incommensurate ferroelastic PMID- 9982032 TI - Criticality and multifractality of the Potts ferromagnetic model on fractal lattices. PMID- 9982034 TI - Critical behavior of the random-field Ising model. PMID- 9982033 TI - Magnetic structure of GdNi2B2C by resonant and nonresonant x-ray scattering. PMID- 9982035 TI - Impurity and doping effects on the pseudoenergy gap in CeNiSn: A Sn NMR study. PMID- 9982036 TI - Elementary excitations in the Delta chain. PMID- 9982037 TI - Quantum solitons in the sawtooth lattice. PMID- 9982039 TI - Magnetic texture determination using nonpolarized neutron diffraction. PMID- 9982038 TI - Self-consistent study of the impurity-doped Mott-Hubbard insulator. PMID- 9982040 TI - Off-equilibrium dynamics in finite-dimensional spin-glass models. PMID- 9982041 TI - Two-magnon scattering and the spin-phonon interaction beyond the adiabatic approximation. PMID- 9982042 TI - Antiferromagnet-ferromagnet transition in the one-dimensional frustrated spin model. PMID- 9982043 TI - Orbital moment and magnetic circular dichroism at the K edge in ferromagnetic cobalt. PMID- 9982044 TI - Muon-spin-rotation measurements in the kagome lattice systems: Cr-jarosite and Fe jarosite. PMID- 9982045 TI - Three-dimensional ordering in bct antiferromagnets due to quantum disorder. PMID- 9982046 TI - U2Pt15Si7: Competition between magnetism and the formation of a heavy-fermion ground state. PMID- 9982048 TI - Magnetic structures of holmium-lutetium alloys and superlattices. PMID- 9982047 TI - Nature of the Verwey transition in magnetite (Fe3O4) to pressures of 16 GPa. PMID- 9982049 TI - History-dependent phenomena in spin-glass mean-field models. PMID- 9982050 TI - Dynamic susceptibility of a reentrant ferromagnet. PMID- 9982051 TI - Equilibrium thermodynamics of cobalt-copper slabs. PMID- 9982053 TI - Optical and magneto-optical properties of Co/Pt multilayers. PMID- 9982052 TI - Evidence for collective spin dynamics above the ordering temperature in La1 xCaxMnO3+ delta. PMID- 9982054 TI - Linear-response theory applied to the dynamics of submicronic magnetic particles. PMID- 9982056 TI - Theory of the bipolar spin switch. PMID- 9982055 TI - Spin-glass and antiferromagnet critical behavior in a diluted fcc antiferromagnet. PMID- 9982057 TI - 151Eu Mossbauer study of transition-metal/Eu multilayers. PMID- 9982058 TI - Vortices in superconducting films: Statistics and fractional quantum Hall effect. PMID- 9982059 TI - Evolution from the vortex state to the critical state in a square-columnar Josephson-junction array. PMID- 9982060 TI - Bosonic and fermionic single-particle states in the Haldane approach to statistics for identical particles. PMID- 9982061 TI - Phase diagram of the unconventional superconductor UPt3 in the weak-crystal-field model. PMID- 9982062 TI - Thermoelectric properties of mesoscopic superconductors. PMID- 9982063 TI - Electronic structure of Ni-substituted Y(Ni1-xMx)2B2C superconductors. PMID- 9982064 TI - Spectrum of resonant plasma oscillations in long Josephson junctions. PMID- 9982065 TI - Suspension of superfluid helium using cesium-coated surfaces. PMID- 9982066 TI - Angular dependence of c-axis plasma frequency and critical current in Josephson coupled superconductors at high fields. PMID- 9982067 TI - Flux-pinning mechanism of proximity-coupled planar defects in conventional superconductors: Evidence that magnetic pinning is the dominant pinning mechanism in niobium-titanium alloy. PMID- 9982068 TI - dc and ac Josephson effect in a superconductor-Luttinger-liquid-superconductor system. PMID- 9982069 TI - Correlated-basis-function analysis of the transverse Ising model. PMID- 9982070 TI - Electron states and electron-phonon coupling in the BEDT-TTF-based organic superconductors. PMID- 9982071 TI - Interaction of vortices with ultrasound and the acoustic Faraday effect in type II superconductors. PMID- 9982072 TI - Supercurrent flow through an effective double-barrier structure. PMID- 9982074 TI - Nonlinear dynamics of vortices in superconductors with short coherence length. PMID- 9982073 TI - Properties of bound, resonant, and regular continuum states of the excitation spectrum of symmetric liquid 4He films at T=0 K. PMID- 9982075 TI - Anomalous Pr ordering in HgSr2PrCu2O6+ delta and the systematic variation of TN(Pr) for the Hg-1212-type systems. PMID- 9982076 TI - Thermal-difference reflectance spectroscopy of the high-temperature cuprate superconductors. PMID- 9982078 TI - ac-susceptibility study of critical current density in metal-substituted ErBa2Cu3O7- delta. PMID- 9982077 TI - Classification of the interlayer coupling in high-Tc cuprates from low-field magnetization studies. PMID- 9982079 TI - Simulation of experimental results on high-Tc superconductors: A phenomenological model. PMID- 9982080 TI - High-frequency behavior of layered superconductors with Josephson coupling. PMID- 9982081 TI - Superconducting order parameter symmetry in multilayer cuprates. PMID- 9982082 TI - Electric-field-dependent variable-range hopping conductance in quasi-two dimensional systems: Application to PrBa2Cu3O7-y-based superconductor-normal metal-superconductor junctions. PMID- 9982083 TI - Zinc-induced modification of the dynamical magnetic susceptibility in the superconducting state of YBa2Cu3O6+x as revealed by inelastic neutron scattering. PMID- 9982084 TI - Localization effects in Co- and Ni-doped Bi2Sr2CaCu2O8+y. PMID- 9982085 TI - Structural, magnetic, and crystalline electric-field effects in single crystals of Y1-xPrxBa2Cu3O7- delta. PMID- 9982086 TI - Charge transfer in high-Tc (Y/Pr)Ba2Cu3O7 superlattices. PMID- 9982088 TI - First-principles investigation of 180 degrees domain walls in BaTiO3. PMID- 9982087 TI - Reply to "Charge transfer in high-Tc (Y/Pr)Ba2Cu3O7 superlattices" PMID- 9982089 TI - Dynamics of the strain-mediated phase transition in KDCO3: A thermal neutron spin echo study. PMID- 9982091 TI - Longitudinal, transverse, and perpendicular magnetoimpedance in nearly zero magnetostrictive amorphous alloys. PMID- 9982090 TI - Interplay of atomic and solid-state effects in inner-shell-resonant photoelectron spectra. PMID- 9982092 TI - Simple method for calculating the speed of sound in tight-binding models: Application to the Su-Schrieffer-Heeger model. PMID- 9982093 TI - Interplay of Jahn-Teller effect and Kondo effect for orbitally degenerate impurity ions. PMID- 9982094 TI - Magnetic x-ray Compton scattering. PMID- 9982096 TI - Infinite number of exponents for a spin-glass transition. PMID- 9982095 TI - Magnetic circular dichroism and orbital momentum coupling in 4d photoemission from Gd(0001). PMID- 9982097 TI - Giant Josephson current through a single bound state in a superconducting tunnel junction. PMID- 9982098 TI - Fractional flux quanta in superconducting solenoids. PMID- 9982099 TI - Gap formation and magnetic ordering in URu2Si2 probed by high-field magnetoresistance. PMID- 9982100 TI - Vortex structure and Josephson supercurrents in stacked double Josephson junctions. PMID- 9982101 TI - Absence of antiferromagnetic correlations in YNi2B2C. PMID- 9982102 TI - Effective mass anisotropy of HgBa2Ca3Cu4O10 measured on a microcrystal by means of miniaturized torque magnetometry. PMID- 9982103 TI - 63,65Cu indirect spin-spin coupling in La1.85Sr0.15CuO4. PMID- 9982105 TI - Large-U cluster-Hamiltonian expansion of the Hubbard model. PMID- 9982104 TI - In-plane and out-of-plane thermal conductivity of a large single crystal of YBa2Cu3O7-x. PMID- 9982106 TI - Semianalytical form for the local-field correction. PMID- 9982107 TI - Band tails, length scales, and localization. PMID- 9982108 TI - Control of the finite-size corrections in exact diagonalization studies. PMID- 9982109 TI - Mixed ultrasoft/norm-conserved pseudopotential scheme. PMID- 9982110 TI - Temperature-dependent photoemission spectral weight in La0.6Sr0.4MnO3. PMID- 9982111 TI - Insulator-to-metal transition in Kondo insulators under a strong magnetic field. PMID- 9982113 TI - Inelastic interaction of nonequilibrium electrons with acoustic phonons at low lattice temperatures. PMID- 9982112 TI - Optical absorption and interband transitions in CePd7. PMID- 9982114 TI - Electron-electron scattering in far-infrared quantum cascade lasers. PMID- 9982115 TI - Gamma -X intervalley-scattering time constant for GaAs estimated from hot electron noise spectroscopy data. PMID- 9982116 TI - Determination of deformation-potential constants from quantum-limit cyclotron resonance linewidths for Ge with anisotropic scattering. PMID- 9982117 TI - Precursor defect to the vacancy-dioxygen center in Si. PMID- 9982118 TI - Time-resolved observation of coherent phonons by the Franz-Keldysh effect. PMID- 9982119 TI - Dispersion theory of the polaron in a quasi-one-dimensional structure. PMID- 9982120 TI - E1 transition in (113)-oriented GaAs/AlAs multiple quantum wells: Confinement effects and optical anisotropy. PMID- 9982121 TI - Structures of atomic steps on the 7 x 7 reconstructed Si(111) surface. PMID- 9982122 TI - Impurity band and magnetic-field-induced metal-insulator transition in a doped GaAs/AlxGa1-xAs superlattice. PMID- 9982123 TI - Phonon strain-shift coefficients of Si1-xGex grown on Ge(001). PMID- 9982124 TI - Reconstructions on the Si(113) surface. PMID- 9982125 TI - Quantum limits on classical permanent memories. PMID- 9982126 TI - Direct determination of exact charge states of surface point defects using scanning tunneling microscopy: As vacancies on GaAs (110). PMID- 9982127 TI - Tight-binding study of optical properties in short-period In0.53Ga0.47As/InP superlattices. PMID- 9982128 TI - Electronic-transport properties of parallel double-ring systems. PMID- 9982129 TI - Landau quantization and the Aharonov-Bohm effect in a two-dimensional ring. PMID- 9982130 TI - Nonlinear piezoelectricity: The effect of pressure on CdTe. PMID- 9982131 TI - Theory of phonon replicas in superlattice photoluminescence excitation spectra. PMID- 9982132 TI - Magneto-optical determination of exciton binding energies in quantum-wire superlattices. PMID- 9982133 TI - Magneto-optics in a square-well quantum dot. PMID- 9982134 TI - Dimensional effects in photoelectron spectra of Ag deposits on GaAs(110) surfaces. PMID- 9982135 TI - Effects of scattering centers on the energy spectrum of a quantum dot. PMID- 9982136 TI - Diffusion of electrons in two-dimensional disordered symplectic systems. PMID- 9982137 TI - Quantum breathing mode for electrons with 1/r2 interaction. PMID- 9982138 TI - Skyrmion liquid in SU(2)-invariant quantum Hall systems. PMID- 9982140 TI - Quantitative theory of third-harmonic generation in an (InAs)0.7(GaSb)0.3/(AlSb) superlattice. PMID- 9982139 TI - Gap shift and bistability in two-dimensional nonlinear optical superlattices. PMID- 9982141 TI - Different quantum behavior of the E1 and E2 spectral structures in Ge nanocrystals. PMID- 9982143 TI - Structure model for the type-C defect on the Si(001) surface. PMID- 9982142 TI - Electron stimulated desorption of negative and positive hydrogen ions from hydrogenated silicon surfaces. PMID- 9982144 TI - Optical properties of the vibrations in charged C60 molecules. PMID- 9982145 TI - van der Waals attraction between simple metal clusters: Core effects using realistic pseudopotentials. PMID- 9982147 TI - Exact treatment of exchange in Kohn-Sham band-structure schemes. PMID- 9982146 TI - Berry phase, hyperorbits, and the Hofstadter spectrum: Semiclassical dynamics in magnetic Bloch bands. PMID- 9982148 TI - Hybridization effects in unoccupied 4f states of Ce compounds. PMID- 9982149 TI - Semiclassical analysis of the quantum interference corrections to the conductance of mesoscopic systems. PMID- 9982151 TI - Green's-function theory for row and periodic defect arrays in photonic band structures. PMID- 9982150 TI - Magnetic circular dichroism of the S 2p, Co 2p, and Co 3p core absorption and orbital angular momentum of the Co 3d state in low-spin CoS2. PMID- 9982152 TI - Derivation of nondiagonal effective dielectric-permeability tensors for magnetized granular composites. PMID- 9982153 TI - Optical sum rules and effective-medium theories for a polycrystalline material: Application to a model for polypyrrole. PMID- 9982154 TI - Electronic properties of strongly correlated states in dicyanoquinonediimine-Cu organic conductors. PMID- 9982155 TI - Anisotropy of the hole drift mobility in barium titanate. PMID- 9982156 TI - 3s2p inelastic x-ray scattering of CaF2. PMID- 9982158 TI - Pressure dependence of the electrical residual resistivity of disordered alloys. PMID- 9982157 TI - Ab initio calculation of electronic structure, crystal field, and intrinsic magnetic properties of Sm2Fe17, Sm2Fe17N3, Sm2Fe17C3, and Sm2Co17. PMID- 9982159 TI - Hexagonal photonic-band-gap structures. PMID- 9982161 TI - Linear-scaling density-functional-theory technique: The density-matrix approach. PMID- 9982160 TI - Andersen's force theorem and the local stress field. PMID- 9982163 TI - Ground-state instabilities in the one-dimensional Penson-Kolb-Hubbard model. PMID- 9982162 TI - t2g versus all 3d localization in LaMO3 perovskites (M=Ti-Cu): First-principles study. PMID- 9982164 TI - Application of empirical interatomic potentials to liquid Si. PMID- 9982166 TI - Deep-level transient-spectroscopy study of rhodium in indium phosphide. PMID- 9982165 TI - Role of radiolytic oxygen in the x-ray production and thermal annealing of defects in high-purity amorphous SiO2. PMID- 9982167 TI - Disordering of natural superlattice in (Ga,In)P induced by electron irradiation. PMID- 9982168 TI - Lattice distortions and electronic structure in the negative silicon vacancy. PMID- 9982169 TI - Effective Hamiltonian and exchange integrals in IV-VI semimagnetic semiconductors at finite temperature. PMID- 9982170 TI - Dynamics of conformational defects in poly(3-hexyl)thiophene. PMID- 9982171 TI - Quantum saturation and condensation of excitons in Cu2O: A theoretical study. PMID- 9982172 TI - Influence of a phonon bath on the hierarchy of electronic densities in an optically excited semiconductor. PMID- 9982174 TI - Investigation of the spatial distribution of dangling bonds in light-soaked hydrogenated amorphous silicon. PMID- 9982173 TI - Contribution of quantum and thermal fluctuations to the elastic moduli and dielectric constants of covalent semiconductors. PMID- 9982175 TI - Band spectra of rectangular graph superlattices. PMID- 9982176 TI - Effects of finite spin-orbit splitting on optical properties of spherical semiconductor quantum dots. PMID- 9982177 TI - Surface plasmon in a two-dimensional Anderson insulator with interactions. PMID- 9982179 TI - Dielectric function of the two-dimensional electron liquid: An analytical fitting. PMID- 9982178 TI - Electron-phonon scattering in a two-dimensional electron gas in a very strong magnetic field near the percolation threshold. PMID- 9982180 TI - Monte Carlo simulations of the spatial transport of excitons in a quantum well structure. PMID- 9982181 TI - Dimer reconstruction and electronic surface states on clean and hydrogenated diamond (100) surfaces. PMID- 9982182 TI - Quasiparticle effective mass for the two- and three-dimensional electron gas. PMID- 9982183 TI - Electronic spectral function for a two-dimensional electron system in the fractional quantum Hall regime. PMID- 9982184 TI - Transient-estimate Monte Carlo in the two-dimensional electron gas. PMID- 9982185 TI - Current fluctuations in a single tunnel junction. PMID- 9982187 TI - Electron-electron interactions and two-dimensional-two-dimensional tunneling. PMID- 9982186 TI - Theory of single-electron tunneling in resonant-tunneling diodes including scattering and multiple subbands at finite temperature. PMID- 9982189 TI - Local aspects of the As-stabilized 2 x 3 reconstructed (001) surface of strained Inx Ga1-xAs alloys: A first-principles study. PMID- 9982188 TI - Enhanced transmission through a disordered potential barrier. PMID- 9982190 TI - Exciton localization by potential fluctuations at the interface of InGaAs/GaAs quantum wells. PMID- 9982191 TI - Low-temperature photoluminescence of disordered thin-layer GaAs/AlAs superlattices: Experiment. PMID- 9982192 TI - Low-temperature photoluminescence of disordered thin-layer GaAs/AlAs superlattices: Kinetic model. PMID- 9982193 TI - Electronic structures of fullerenes Cn with Ih symmetry and n=20k2. PMID- 9982195 TI - Bending of a film-substrate system by epitaxy. PMID- 9982194 TI - Morphology of islanded transition-metal films on graphite studied by extreme-UV reflectivity. PMID- 9982196 TI - Chemisorption and fragmentation of C60 on Pt(111) and Ni(110). PMID- 9982197 TI - Atomic arrangement at the AlN/SiC interface. PMID- 9982198 TI - Substrate and hydrogen phonons of the ordered p(2 x 1) and (2 x 2) phase and of the anomalous (1 x 1) phase of hydrogen on W(110). PMID- 9982199 TI - Adsorption, migration, and superlattice formation of benzene on Pd(110). PMID- 9982200 TI - Ultraviolet photoelectron spectra of C86 and C90. PMID- 9982201 TI - First-layer island growth during epitaxy. PMID- 9982203 TI - Energy and angular distributions of hyperthermal-energy Li+ scattered from Cu(001). PMID- 9982202 TI - Effects of carbon on Fe-grain-boundary cohesion: First-principles determination. PMID- 9982204 TI - Excitation of phonons in medium-energy electron diffraction. PMID- 9982205 TI - High-resolution 13C NMR study of oxygen intercalation in C60. PMID- 9982206 TI - Dry friction in the Frenkel-Kontorova-Tomlinson model: Static properties. PMID- 9982207 TI - Comment on "Density-functional description of the electronic structure of LaMO3 (M=Sc, Ti, V, Cr, Mn, Fe, Co, Ni)" PMID- 9982208 TI - Comment on "Structure of the Mn-induced Cu(100) c(2 x 2) surface" PMID- 9982209 TI - Erratum: Nyquist noise in the transition from mesoscopic to macroscopic transport PMID- 9982210 TI - Magnetoconductance anisotropy and interference effects in variable-range hopping. PMID- 9982211 TI - Photoemission study of itinerant ferromagnet Cr1- delta Te. PMID- 9982213 TI - Time-dependent specific heat below 1 K in the spin-density-wave state of (TMTSF)2PF6. PMID- 9982212 TI - Ab initio electric-field gradients and electron densities at 27Al, 57Fe, and 67Zn in the spinels ZnAl2O4 and ZnFe2O4. PMID- 9982214 TI - Singularity of the density of states in the two-dimensional Hubbard model from finite-size scaling of Yang-Lee zeros. PMID- 9982215 TI - Compton-scattering study of the electronic properties of the transition-metal alloys FeAl, CoAl, and NiAl. PMID- 9982216 TI - Manipulation of the spin-orbit coupling using the Dirac equation for spin dependent potentials. PMID- 9982218 TI - Interstitial-oxygen-atom diffusion in MgO. PMID- 9982217 TI - Ab initio pseudopotentials for interacting atoms. PMID- 9982220 TI - Mechanism and kinetics of the ion-assisted nucleation in amorphous silicon. PMID- 9982219 TI - Behavior of silicon-, sulfur-, and tellurium-related DX centers in liquid-phase epitaxy and vapor-phase-epitaxy GaAs1-xPx alloys. PMID- 9982221 TI - Hydrogen migration in polycrystalline silicon. PMID- 9982223 TI - Lattice properties of strained GaAs, Si, and Ge using a modified bond-charge model. PMID- 9982222 TI - Photoemission study of amorphous carbon modifications and comparison with calculated densities of states. PMID- 9982224 TI - Transport analysis of the thermalization and energy relaxation of photoexcited hot electrons in Ge-doped GaAs. PMID- 9982225 TI - Optical-absorption spectrum near the exciton band edge in CuGaS2 at 5 K. PMID- 9982227 TI - Model and results for a deep level with two different configurations in Hg0.3Cd0.7Te. PMID- 9982226 TI - Evidence for correlated hole distribution in neutron-transmutation-doped isotopically controlled germanium. PMID- 9982228 TI - Lifetimes of positrons trapped at Si vacancies. PMID- 9982229 TI - Hot-carrier energy-loss rates in alloy semiconductors. PMID- 9982230 TI - Energy barrier to reorientation of the substitutional nitrogen in diamond. PMID- 9982232 TI - Dopant and carrier concentration in Si in equilibrium with monoclinic SiP precipitates. PMID- 9982231 TI - Point defects and their reactions in e--irradiated GaAs investigated by x-ray diffraction methods. PMID- 9982233 TI - Multiple-channel resonant tunneling in a tunneling junction with an impurity cluster. PMID- 9982234 TI - Role of structural saturation and geometry in the luminescence of silicon-based nanostructured materials. PMID- 9982235 TI - Donor levels and the microscopic structure of the DX center in n-type Si-doped AlxGa0.51-xIn0.49P grown by molecular-beam epitaxy. PMID- 9982236 TI - Kink-induced buckled dimers on Si(001) and Ge(001) at room temperature studied by scanning tunneling microscopy. PMID- 9982237 TI - Absolute transmission, reflection, and absorption studies in GaAs/AlAs quantum wells containing a photoexcited electron gas. PMID- 9982238 TI - Surface roughening during low-temperature Si epitaxial growth on singular vs vicinal Si(001) substrates. PMID- 9982240 TI - Resonant-mode conversion and transmission of phonons in superlattices. PMID- 9982239 TI - Reconstruction-dependent electron-hole recombination on GaAs(001) surfaces studied by using near-surface quantum wells. PMID- 9982241 TI - X-ray scattering in disordered superlattices: Theory and application to FeF2/ZnF2 superlattices. PMID- 9982242 TI - Single-electron tunneling through a double quantum dot: The artificial molecule. PMID- 9982243 TI - Intersubband resonances in InAs/AlSb quantum wells: Selection rules, matrix elements, and the depolarization field. PMID- 9982244 TI - Temperature and density dependence of the electron Lande g factor in semiconductors. PMID- 9982245 TI - Atomic and electronic structures of oxygen-adsorbed Si(001) surfaces. PMID- 9982246 TI - Static and dynamic properties of coupled electron-electron and electron-hole layers. PMID- 9982247 TI - Crossover in tunneling hops in systems of strongly localized electrons. PMID- 9982248 TI - Hopping conduction in semiconductor superlattices in a quantized magnetic field. PMID- 9982249 TI - Photoluminescence studies of current-induced nonequilibrium states in magnetically quantized two-dimensional electron gases. PMID- 9982250 TI - Successes and failures of the k PMID- 9982251 TI - Coulomb drag of edge excitations in the Chern-Simons theory of the fractional quantum Hall effect. PMID- 9982253 TI - Coherent magnetotransport in confined arrays of antidots. I. Dispersion relations and current densities. PMID- 9982252 TI - Time-resolved transport between resonantly coupled Landau levels in semiconductor superlattices. PMID- 9982254 TI - Coherent magnetotransport in confined arrays of antidots. II. Two-terminal conductance. PMID- 9982255 TI - Structure determination of a Sb monolayer on Ge(111) from first-principles calculations. PMID- 9982256 TI - Growth of Co on a stepped and on a flat Cu(001) surface. PMID- 9982257 TI - Molecular-dynamics investigation of early film growth of Pt/Au(100) and Au/Pt(100) and an interdiffusive growth mode. PMID- 9982258 TI - Density-functional periodic study of the adsorption of hydrogen on a palladium (111) surface. PMID- 9982259 TI - Electronic structure of small copper oxide clusters: From Cu2O to Cu2O4. PMID- 9982260 TI - Angle-resolved photoemission study of SrTiO3 (100) and (110) surfaces. PMID- 9982261 TI - Atomic-structure determination of diamond using Auger-electron diffraction. PMID- 9982262 TI - Exciton-induced lattice relaxation and the electronic and vibrational spectra of silicon clusters. PMID- 9982263 TI - Embedding approach to the isolated adsorbate. PMID- 9982265 TI - Kinetic roughening of surfaces: Derivation, solution, and application of linear growth equations. PMID- 9982264 TI - Identification of electrostatic and van der Waals interaction forces between a micrometer-size sphere and a flat substrate. PMID- 9982266 TI - Interaction of Rydberg atoms with a metal surface in the presence of an external electric field. PMID- 9982268 TI - Spin-polarized tunneling with GaAs tips in scanning tunneling microscopy. PMID- 9982267 TI - Photoelectrical properties of semiconductor tips in scanning tunneling microscopy. PMID- 9982269 TI - Strain-induced growth-mode transition of V in epitaxial Mo/V(001) superlattices. PMID- 9982270 TI - Linear-response calculation of electron-phonon coupling parameters. PMID- 9982271 TI - Optically detected magnetic-resonance study of triplet-state dynamics in C70. PMID- 9982273 TI - Infrared absorption related to the metastable state of arsenic antisite defects in electron-irradiated GaAs. PMID- 9982272 TI - Electronic structure and the metal-insulator transition in NiS2-xSex. PMID- 9982274 TI - Determination of the limiting mobility of a two-dimensional electron gas in AlxGa1-xAs/GaAs heterostructures and direct measurement of the energy relaxation time. PMID- 9982275 TI - Measurements of a composite fermion split-gate device. PMID- 9982276 TI - Shubnikov-de Haas oscillations in a two-dimensional electron gas in a spatially random magnetic field. PMID- 9982277 TI - Nonlinear electron-wave directional coupler. PMID- 9982278 TI - Optical second-harmonic electroreflectance spectroscopy of a Si(001) metal-oxide semiconductor structure. PMID- 9982279 TI - Scaling of surface roughness in a heterogeneous film growth system: GexSi1-x on Si. PMID- 9982280 TI - Phase diagram of vortices in double-layer quantum Hall systems. PMID- 9982281 TI - Spectral correlation and response functions in quantum dots. PMID- 9982283 TI - Electronic conduction through organic molecules. PMID- 9982282 TI - Microscopic study of the pressure-induced structural phase transition of ZnTe. PMID- 9982284 TI - Theory of Andreev reflection in a junction with a strongly disordered semiconductor. PMID- 9982286 TI - Instability of the disordered critical points of Dirac fermions. PMID- 9982285 TI - Nonequilibrium optical-phonon population by sequential resonant tunneling in GaAs AlAs superlattices. PMID- 9982287 TI - Photoluminescence decay times in strong-coupling semiconductor microcavities. PMID- 9982289 TI - Negative-electron-affinity effect on the surface of chemical-vapor-deposited diamond polycrystalline films. PMID- 9982288 TI - Influence of island mobility on island size distributions in surface growth. PMID- 9982290 TI - One-dimensional commensurate-incommensurate transition: Bromide on the Au(100) electrode. PMID- 9982291 TI - Trapped electrons in solid deuterium. PMID- 9982293 TI - Far-infrared reflectivity and Raman spectra of Ba5Nb4O15. PMID- 9982292 TI - Thermal expansion of chromium at high temperature. PMID- 9982295 TI - Electron-beam analysis of polymerized KC60. PMID- 9982294 TI - Evidence for correlation effects in Sr2RuO4 from resonant and x-ray photoemission spectroscopy. PMID- 9982296 TI - Inversion and the phase problem in specular reflection. PMID- 9982297 TI - Interfaces in the Ising quantum chain and conformal invariance. PMID- 9982298 TI - Bond hybridization in Au alloys: Extracting structural information from the x-ray absorption white line. PMID- 9982300 TI - Evidence for a supercooled plastic-crystal phase in solid ethanol. PMID- 9982299 TI - Fluctuation effects in the Ising model with reduced interaction and quenched disorder. PMID- 9982301 TI - Theoretical study of Fe-Mn-Al alloys in the fcc disordered phase. PMID- 9982303 TI - Dynamical replica theory for disordered spin systems. PMID- 9982302 TI - Pressure-induced polymerization of fullerenes: A comparative study of C60 and C70. PMID- 9982304 TI - Kondo resonance energies in CePd3. PMID- 9982306 TI - Quasi-one-dimensional organic unsaturated ferromagnetism: Some rigorous results. PMID- 9982305 TI - Variational analyses of series expansions for the exchange-interaction model. PMID- 9982308 TI - Semiclassical transport theory of inhomogeneous systems. PMID- 9982307 TI - Chemical pressure effects on the crystallographic and magnetic behavior of CeNiGa3. PMID- 9982309 TI - Magnetoresistance in La1-xSrxCoO3 for 0.05 <~ x <~ 0.25. PMID- 9982310 TI - Critical behavior of a quantum spherical model in a random field. PMID- 9982311 TI - Short-range Potts spin-glass model: Renormalization-group method. PMID- 9982312 TI - Core-level magnetic-circular-dichroism study of an Fe single crystal, Fe-Pt alloys, and an Fe/Pt multilayer. PMID- 9982313 TI - Curie-temperature enhancement of ferromagnetic phases in nanoscale heterogeneous systems. PMID- 9982314 TI - Interfacial roughness, correlation length, and giant magnetoresistances in NiFeCo/Cu superlattices. PMID- 9982315 TI - Statistical interactions of vortices in superconducting films. PMID- 9982316 TI - Quantitative analysis of Josephson-quasiparticle current in superconducting single-electron transistors. PMID- 9982317 TI - Effect of pressure on the superconducting Tc of lanthanum. PMID- 9982318 TI - Superconductivity in heavy-fermion CeRh2Si2. PMID- 9982319 TI - Splitting of the resistive transition of copper oxide superconductors: Intrinsic double superconducting transitions versus extrinsic effects. PMID- 9982320 TI - Evidence for a non-s-wave superconducting order parameter in YBa2Cu3O6.6 with Tc=60 K. PMID- 9982321 TI - Model of c-axis resistivity of high-Tc cuprates. PMID- 9982323 TI - Ab initio pseudopotential study of the structural phase transformations of ZnS under high pressure. PMID- 9982322 TI - Mechanism of tritium diffusion in lithium oxide. PMID- 9982324 TI - Observation of planar oscillations of MeV protons in silicon using ion channeling patterns. PMID- 9982325 TI - Model-independent determination of the strain distribution for a Si0.9Ge0.1/Si superlattice using x-ray diffractometry data. PMID- 9982326 TI - Observation of persistent spectral hole burning of Eu3+ in beta "-alumina at 110 K. PMID- 9982328 TI - Thermal properties of iron at high pressures and temperatures. PMID- 9982327 TI - Effect of melting and electron-phonon coupling on the collapse of depleted zones in copper, nickel, and alpha -iron. PMID- 9982329 TI - Fourth-order contributions to the 7F6-->5D4 two-photon transition of Tb3+ in a cubic lattice. PMID- 9982330 TI - Phonon density of states and low-temperature specific heat of quasi-one dimensional (TaSe4)2I and (NbSe4)3I. PMID- 9982331 TI - Unusual low-frequency elastic anomalies around the upper incommensurate phase of PMID- 9982332 TI - Compressibility of C60 in the temperature range 150-335 K up to a pressure of 1 GPa. PMID- 9982333 TI - Structural investigations of the amorphous alloy Al30Ge70 under high pressure. PMID- 9982334 TI - Localization of electromagnetic waves in two-dimensional disordered systems. PMID- 9982335 TI - Glass transition of associated solvents studied by fluorescence measurement of doped chromophores. PMID- 9982336 TI - Resonant neutron scattering from certain anharmonic potentials. PMID- 9982337 TI - Branching ratio of uv and blue upconversions of Tm3+ ions in glasses. PMID- 9982338 TI - Microstructural analysis of simulated liquid and amorphous Ni. PMID- 9982339 TI - Two-matrix models and their possible relevance to disordered systems. PMID- 9982340 TI - Time and composition dependence of mechanical alloying of Fe1-xSnx. PMID- 9982341 TI - Solidification kinetics in SiGe alloys. PMID- 9982342 TI - Elastic interfacial waves in discrete and continuous media. PMID- 9982343 TI - Brownian-motion model of parametric correlations in ballistic cavities. PMID- 9982344 TI - Fock-space approach to the kinetic Ising model. PMID- 9982345 TI - Cooperative Jahn-Teller effect and electron-phonon coupling in La1-xAxMnO3. PMID- 9982346 TI - Concentration dependence of optical phonons in the TiO2-SnO2 system. PMID- 9982347 TI - Variational study of the discrete Holstein model. PMID- 9982348 TI - Validity of the discrete nonlinear Schrodinger equation in the context of the fluorescence depolarization of a spin-boson system. PMID- 9982350 TI - Electronic band structure in a periodic magnetic field. PMID- 9982349 TI - Spin scattering in ferromagnetic thin films. PMID- 9982351 TI - Magnetic behavior of stoichiometric and nonstoichiometric GdAs single crystals. PMID- 9982352 TI - Spin-wave excitation in a quasi-one-dimensional organic ferromagnet. PMID- 9982353 TI - Numerical study of the random transverse-field Ising spin chain. PMID- 9982354 TI - Magnetic anisotropy and weak ferromagnetism of single-crystal TbNi2B2C. PMID- 9982355 TI - Magnetic structure of TbNi2B2C. PMID- 9982356 TI - Quantum-well states and induced magnetism in Fe/CuN/Fe bcc (001) trilayers. PMID- 9982357 TI - Random magnetic order in Al-Mn liquids. PMID- 9982358 TI - Antiferromagnetic spin ladders: Crossover between spin S=1/2 and S=1 chains. PMID- 9982360 TI - Lifetime of vortices in two-dimensional easy-plane ferromagnets. PMID- 9982359 TI - Temperature-dependent pitch and phase diagram for incommensurate XY spins in a slab geometry. PMID- 9982361 TI - Effects of magnetic order on the upper critical field of UPt3. PMID- 9982362 TI - H-T phase diagrams of the double transition in thoriated UBe13. PMID- 9982363 TI - Nucleation of vortices inside open and blind microholes. PMID- 9982364 TI - Exact results on superconductivity due to interband coupling. PMID- 9982365 TI - Monte Carlo calculation of the current-voltage characteristics of a two dimensional lattice Coulomb gas. PMID- 9982366 TI - Infrared conductivity of a dx2-y2-wave superconductor with impurity and spin fluctuation scattering. PMID- 9982367 TI - Two-order-parameter phenomenological theory of the phase diagram of liquid helium. PMID- 9982368 TI - Finite bandwidth effects on the transition temperature and NMR relaxation rate of impure superconductors. PMID- 9982369 TI - Interface-potential approach to surface states in type-I superconductors. PMID- 9982370 TI - Strong rare-earth size dependence of Tc in RSr2Cu2.85Re0.15Oz. PMID- 9982371 TI - Mixed-state Hall-effect studies in high-Tc-superconducting (YBa2Cu3O7- delta )n/(PrBa2Cu3O7- delta )m superlattices. PMID- 9982373 TI - Resonant magnon Raman scattering in PrBa2Cu3O7 single crystals. PMID- 9982372 TI - X-ray-induced photoconductivity in YBa2Cu3O6 between 70 and 300 K. PMID- 9982374 TI - Current transport and electronic states in a,b-axis-oriented YBa2Cu3O7/PrBa2Cu3O7/YBa2Cu3O7 sandwich-type junctions. PMID- 9982376 TI - Critical fluctuations and lowest-Landau-level scaling of the specific heat of high-temperature superconductors. PMID- 9982375 TI - Raman study of crystal-field excitations in Nd1.85Ce0.15CuO4. PMID- 9982377 TI - Theory of flux penetration into thin films with field-dependent critical current. PMID- 9982379 TI - Matching and surface barrier effects of the flux-line lattice in superconducting films and multilayers. PMID- 9982378 TI - Comparison of the low-temperature specific heat of Fe- and Co-doped Bi1.8Pb0.2Sr2Ca(Cu1-xMx)2O8 (M=Fe or Co): Anomolously enhanced electronic contribution due to Fe doping. PMID- 9982380 TI - Charged domain-wall dynamics in doped antiferromagnets and spin fluctuations in cuprate superconductors. PMID- 9982381 TI - Unusual magnetic-field dependence of the electrothermal conductivity in the mixed state of cuprate superconductors. PMID- 9982382 TI - Magneto-optical study of flux penetration and critical current densities in PMID- 9982383 TI - Anisotropy in magnetic dynamics of YBa2Cu3O7. PMID- 9982385 TI - Bilayers of chiral spin states. PMID- 9982384 TI - T-matrix formulation of impurity scattering in correlated systems. PMID- 9982386 TI - Theory of inelastic x-ray scattering in layered superconductors. PMID- 9982388 TI - Method for determining the critical-state response of superconductors in tape geometry. PMID- 9982387 TI - In-plane and out-of-plane magnetoresistance in La2-xSrxCuO4 single crystals. PMID- 9982389 TI - Effective single-band models for the high-Tc cuprates. I. Coulomb interactions. PMID- 9982391 TI - Erratum: Soliton excitations in one-dimensional diatomic lattices PMID- 9982390 TI - Effective single-band models for the high-Tc cuprates. II. Role of apical oxygen. PMID- 9982392 TI - Erratum: Anisotropy and dimensional crossover of the vortex state in Bi2Sr2CaCu2O8+ delta crystals PMID- 9982393 TI - Degenerate Blume-Emery-Griffiths model for the martensitic transformation. PMID- 9982394 TI - Channeling radiation of electrons in natural diamond crystals and their coherence and occupation lengths. PMID- 9982395 TI - Surface-induced ordering and disordering in face-centered-cubic alloys: A Monte Carlo study. PMID- 9982397 TI - Holographic recording and beam coupling in ferroelectric Bi4Ti3O12. PMID- 9982396 TI - Molecular-dynamics study of partial edge dislocations in copper and gold: Interactions, structures, and self-diffusion. PMID- 9982398 TI - Local-density-functional calculations for defect interactions in Al. PMID- 9982400 TI - Consistent partial structure factors for amorphous Ni0.33(ZryHf1-y)0.67 using x ray and neutron diffraction. PMID- 9982399 TI - Systematics in the commensurate-incommensurate phase transition in PMID- 9982401 TI - Contribution of the vibrational free energy to phase stability in substitutional alloys: Methods and trends. PMID- 9982402 TI - Icosahedral quasicrystal decoration models. I. Geometrical principles. PMID- 9982403 TI - Icosahedral quasicrystal decoration models. II. Optimization under realistic Al Mn potentials. PMID- 9982404 TI - Partial disorder and molecular motion of 4-chlorobiphenyl studied by 35Cl NQR and Raman spectroscopy. PMID- 9982406 TI - Completely quantized theory of homogeneous line broadening in long-lived nuclear states. PMID- 9982405 TI - Lattice dynamics of II-VI materials using the adiabatic bond-charge model. PMID- 9982407 TI - Beyond the isotropic-model approximation in the theory of thermal conductivity. PMID- 9982408 TI - Time-retarded interactions in systems with tunneling states and strong electron phonon coupling. PMID- 9982409 TI - Ab initio molecular-dynamics study of diffusion and defects in solid Li3N. PMID- 9982410 TI - Ab initio calculations of interaction energies of magnetic layers in noble metals: Co/Cu(100). PMID- 9982411 TI - Enhanced giant magnetoresistance in spin-valves sandwiched between insulating NiO. PMID- 9982412 TI - Quantum-well states in Cu/Co overlayers and sandwiches. PMID- 9982413 TI - Induced magnetization in thin epitaxial V films on Fe (100). PMID- 9982414 TI - Oscillatory magnetoresistance in the charge-transfer salt beta "-(BEDT-TTF)2AuBr2 in magnetic fields up to 60 T: Evidence for field-induced Fermi-surface reconstruction. PMID- 9982415 TI - 13C NMR of the organic ferromagnet TDAE-C60. PMID- 9982416 TI - Magnetic properties of the ZnFe2O4 spinel. PMID- 9982418 TI - Quantum phase transition in square- and triangular-lattice spin-1/2 antiferromagnets. PMID- 9982417 TI - Scaling theory of the Kondo screening cloud. PMID- 9982419 TI - Absence of gap for infinite half-integer spin ladders with an odd number of legs. PMID- 9982421 TI - Theory of nuclear magnetic relaxation in Haldane-gap antiferromagnets. PMID- 9982420 TI - Anomalous moment and anisotropy behavior in Fe3O4 films. PMID- 9982423 TI - Magneto-optical Kerr effect in a paramagnetic overlayer on a ferromagnetic substrate: A spin-polarized quantum size effect. PMID- 9982422 TI - Calculated spin and orbital moments in the surfaces of the 3d metals Fe, Co, and Ni and their overlayers on Cu(001). PMID- 9982424 TI - Dynamical critical transition of an antiferromagnetic Ising model in an oscillating field. PMID- 9982426 TI - Nonlinear spin dynamics in nuclear magnets. PMID- 9982425 TI - Ferromagnetism in correlated electron systems: Generalization of Nagaoka's theorem. PMID- 9982427 TI - Magnetic properties of 4d transition-metal clusters. PMID- 9982428 TI - Phase-coherent conductance of a superconductor-normal-metal quantum interferometer. PMID- 9982429 TI - Enhanced nonlinear response of superconductor-normal-conductor composite wires and strips. PMID- 9982430 TI - Low-field vortex dynamics over seven time decades in a Bi2Sr2CaCu2O8+ delta single crystal for temperatures 13 <~ T <~ 83 K. PMID- 9982431 TI - Transition between different quantum states in a mesoscopic system: The superconducting ring. PMID- 9982432 TI - Critical fields and mixed-state properties of the layered organic superconductor kappa -(BEDT-TTF)2I3. PMID- 9982433 TI - Diffusive and ballistic motion in superconducting hybrid structures. PMID- 9982434 TI - Deviations from Fermi-liquid behavior in (2+1)-dimensional quantum electrodynamics and the normal phase of high-Tc superconductors. PMID- 9982435 TI - Flux motion and phase transitions in superconducting (K,Ba)BiO3 single crystals. PMID- 9982436 TI - Conserving and gapless approximations for an inhomogeneous Bose gas at finite temperatures. PMID- 9982437 TI - Observation of both pair and quasiparticle tunneling in intrinsic junction stacks fabricated on Bi2Sr2CaCu2O8+ delta single crystals. PMID- 9982438 TI - Far-infrared c-axis response of La1.87Sr0.13CuO4 determined by ellipsometry. PMID- 9982439 TI - Energy-gap structure of a t-J bilayer. PMID- 9982440 TI - Nonresonant microwave absorption study of intrinsic Josephson coupling in Bi2Sr2CaCu2O8 single crystals. PMID- 9982441 TI - Local density of states of quasiparticles near the interface of nonuniform d-wave superconductors. PMID- 9982443 TI - Stability analysis of a model for the defect structure of YBa2Cu3Ox. PMID- 9982442 TI - Magnetic ordering in PrBa2Cu3-yAlyO6+x. PMID- 9982444 TI - Observation of dynamic flux-line relaxation in ion-irradiated Bi2Sr1.8CaCu2Ox by Lorentz microscopy. PMID- 9982446 TI - Near-edge x-ray-absorption study of transition-metal-implanted YBa2Cu3O7- delta. PMID- 9982445 TI - Sign reversal of the Hall resistivity of single-crystalline Bi1.95Sr1.65La0.4CuO6+ delta and Bi2Sr2CaCu2O8+ delta. PMID- 9982447 TI - Resistivity and Hall effect of metallic oxygen-deficient YBa2Cu3Ox films in the normal state. PMID- 9982448 TI - Imaginary part of the optical conductivity of Ba1-xKxBiO3. PMID- 9982449 TI - Synthesis of Ba1-xKxBiO3 ceramic specimens: Electron paramagnetic resonance and microwave absorption. PMID- 9982450 TI - Quadruple perovskites L'L"Ba2Cu2Ti2O11 as good candidates for high-temperature superconductors: Role of oxygen defects. PMID- 9982451 TI - Vortex pinning in the frozen vortex lattice in YBa2Cu3O7-x films. PMID- 9982452 TI - Three-dimensional superconducting behavior and thermodynamic parameters of HgBa2Ca0.86Sr0.14Cu2O6- delta. PMID- 9982453 TI - Comment on "X-ray-absorption fine structure in embedded atoms" PMID- 9982454 TI - Reply to "Comment on 'x-ray-absorption fine structure in embedded atoms' " PMID- 9982455 TI - Comment on "Theory of giant magnetoresistance effects in Fe/Cr multilayers: Spin dependent scattering from impurities" PMID- 9982456 TI - Comment on "Flux flow and flux cutting in type-II superconductors carrying a longitudinal current" PMID- 9982457 TI - Transient absorption of vibrationally excited FH(CN-) centers in cesium halides: Insight into the electronic-to-vibrational energy transfer. PMID- 9982458 TI - Quartzlike polymorph of ice. PMID- 9982459 TI - Dominant role of E' centers in x-ray-induced, visible luminescence in high-purity amorphous silicas. PMID- 9982460 TI - Homogeneous linewidth of the 5D0-7F0 transition of trivalent europium in a fluorophosphate glass. PMID- 9982461 TI - Soft-x-ray fluorescence study of buried silicides in antiferromagnetically coupled Fe/Si multilayers. PMID- 9982462 TI - Spin and charge gaps in the one-dimensional Kondo-lattice model with Coulomb interaction between conduction electrons. PMID- 9982463 TI - Kondo effect in a Luttinger liquid: A boundary-conformal-field-theory approach. PMID- 9982465 TI - Double degeneracy and Jahn-Teller effects in colossal-magnetoresistance perovskites. PMID- 9982464 TI - Metal-insulator transition in ammoniated K3C60. PMID- 9982466 TI - Calculation of the magnetoresistance in RhFe. PMID- 9982467 TI - Phase transitions in the Heisenberg spin ladder with ferromagnetic legs. PMID- 9982468 TI - Nonlinear dynamics of magnetic vortices in single-crystal and ion-damaged NbSe2. PMID- 9982469 TI - Columnar defects and vortex fluctuations in layered superconductors. PMID- 9982471 TI - Optical conductivity of a t-J ladder. PMID- 9982470 TI - Far-infrared transmission study on Nd1.85Ce0.15CuO4-y thin films. PMID- 9982472 TI - First-order superconductor-to-insulator transition: Evidence for a supersolid phase. PMID- 9982474 TI - Electronic structure of insulating salts of the kappa -(BEDT-TTF)2X family studied by low-temperature specific-heat measurements. PMID- 9982473 TI - de Haas-van Alphen study in the superconducting state of YNi2B2C. PMID- 9982476 TI - epsilon expansion of the conductivity at the superconductor-Mott-insulator transition. PMID- 9982475 TI - Highly anisotropic superconductivity in the organic conductor alpha -(BEDT TTF)2NH4Hg(SCN)4. PMID- 9982477 TI - Strong temperature dependence of the c-axis gap parameter of Bi2Sr2CaCu2O8+ delta intrinsic Josephson junctions. PMID- 9982478 TI - Thermal noise in superconducting quantum point contacts. PMID- 9982480 TI - Vortex plastic flow, local flux density, magnetization hysteresis loops, and critical current, deep in the Bose-glass and Mott-insulator regimes. PMID- 9982479 TI - Amplification of the c-axis vortex correlation by twin-boundary pinning at the vortex liquid-solid phase transition. PMID- 9982481 TI - Transport properties of Bi2Sr2CuO6 single crystals: Possibility of interplane coupling in the weakly localized regime. PMID- 9982483 TI - Change of parity of the order parameter in high-temperature superconductors due to impurities. PMID- 9982482 TI - 63Cu NMR probe of superconducting properties in HgBa2Ca2Cu3O8+ delta : A possible reason for Tc=133 K. PMID- 9982484 TI - Optical conductivity of the U= PMID- 9982485 TI - Evidence for strong interaction between the 5f 2 and 5f 17p1 configurations of U4+ in the octahedral sites of Cs2UBr6 and Cs2ZrBr6. PMID- 9982486 TI - Symmetrization of atomic forces within the full-potential linearized augmented plane-wave method. PMID- 9982487 TI - Nonlocal kinetic-energy-density functionals. PMID- 9982488 TI - Evolution of carrier density in the series YCu5-xInx. PMID- 9982490 TI - Ferromagnetic superexchange in Cr-based diluted magnetic semiconductors. PMID- 9982489 TI - Effects of electrically active impurities on the bond energy in silicon: Ab initio total energy cluster study. PMID- 9982491 TI - Magnetic-field-induced crossover from Mott variable-range hopping to weakly insulating behavior. PMID- 9982493 TI - Geometrical effect on the electron escape rate in a mesoscopic ring with an Aharonov-Bohm magnetic flux. PMID- 9982492 TI - The s-d and p-d exchange interaction in Zn1-xFexTe. PMID- 9982494 TI - Degeneracy of Landau levels and quantum group slq(2). PMID- 9982495 TI - Dispersion of optical second-harmonic generation of Si(111) 7 x 7 during oxygen adsorption. PMID- 9982496 TI - Dependence of tunneling transparency of the disordered superlattice on the parameters of impurity centers located inside the barriers. PMID- 9982497 TI - Current-carrying ground states in mesoscopic and macroscopic systems. PMID- 9982499 TI - Experimental manifestation of the effect of disorder on exciton binding energy in mixed crystals. PMID- 9982498 TI - D- centers probed by resonant tunneling spectroscopy. PMID- 9982500 TI - Magnetic-field dependence of exciton spin relaxation in GaAs/AlxGa1-xAs quantum wells. PMID- 9982501 TI - Coupling of lateral and vertical electron motion in GaAs-AlxGa1-xAs quantum wires and dots. PMID- 9982502 TI - Weak and strong localization in low-dimensional semiconductor structures. PMID- 9982504 TI - Photon drag effect in tunnel-coupled quantum wells. PMID- 9982503 TI - Generation of spin-polarized currents in Zeeman-split Tomonaga-Luttinger models. PMID- 9982505 TI - Pseudopotential calculations of nanoscale CdSe quantum dots. PMID- 9982506 TI - Phase rigidity and h/2e oscillations in a single-ring Aharonov-Bohm experiment. PMID- 9982507 TI - Photoluminescence of the two-dimensional hole gas in p-type delta -doped Si layers. PMID- 9982509 TI - Single-mode quantum wires. PMID- 9982508 TI - Hofstadter-type energy spectra in lateral superlattices defined by periodic magnetic and electrostatic fields. PMID- 9982510 TI - Composite-fermion excitations and the electronic spectra of fractional quantum Hall systems. PMID- 9982511 TI - Ballistic composite fermions in semiconductor nanostructures. PMID- 9982512 TI - Mapping connectivity in discontinuous metal films with a scanning tunneling microscope. PMID- 9982513 TI - Transformation of a graphite superlattice into triangular dislocations. PMID- 9982514 TI - Helium-atom-scattering measurements of surface-phonon dispersion curves of the C(111)-H(1 x 1) surface. PMID- 9982515 TI - Simulation model for self-ordering of strained islands in molecular-beam epitaxy. PMID- 9982516 TI - Multielectron neutralization channels in ion-surface scattering. PMID- 9982518 TI - Localization in quasi-one-dimensional systems with a random magnetic field. PMID- 9982517 TI - Electronic structure of CuV2S4. PMID- 9982519 TI - Optimized wave functions for quantum Monte Carlo studies of atoms and solids. PMID- 9982521 TI - Dirac fermions with disorder in two dimensions: Exact results. PMID- 9982520 TI - Direct k-space photoemission imaging of the Fermi surface of Cu. PMID- 9982522 TI - Ab initio electronic structure, magnetism, and magnetocrystalline anisotropy of UGa2. PMID- 9982523 TI - Polarons and bipolarons in strongly interacting electron-phonon systems. PMID- 9982524 TI - Quantum Monte Carlo study of the one-dimensional Holstein model of spinless fermions. PMID- 9982525 TI - Monte Carlo simulations of the charged boson fluid at T=0. PMID- 9982526 TI - Quantum group, Bethe ansatz equations, and Bloch wave functions in magnetic fields. PMID- 9982527 TI - Dynamics of a heavy particle in a Luttinger liquid. PMID- 9982528 TI - Model for quantitative analysis of reflection-electron-energy-loss spectra: Angular dependence. PMID- 9982529 TI - Experimental test of model for angular and energy dependence of reflection electron-energy-loss spectra. PMID- 9982530 TI - Ab initio investigation of the structure and electronic properties of the energetic solids TATB and RDX. PMID- 9982531 TI - Photoluminescence and optical absorption in neutron-irradiated crystalline quartz. PMID- 9982532 TI - Electronic structure anisotropy and d-configuration in Ni-based materials. PMID- 9982533 TI - Non-Gaussian 1/f noise: Experimental optimization and separation of high-order amplitude and phase correlations. PMID- 9982535 TI - Strong-coupling expansion for the Hubbard model in arbitrary dimension using slave bosons. PMID- 9982534 TI - First-principles free-energy calculations on condensed-matter systems: Lattice vacancy in silicon. PMID- 9982537 TI - Influence of gradient corrections to the local-density-approximation on the calculation of hyperfine fields in ferromagnetic Fe, Co, and Ni. PMID- 9982536 TI - Overlayer-induced anomalous interface magnetocrystalline anisotropy in ultrathin Co films. PMID- 9982538 TI - Energetics and hydrogen passivation of carbon-related defects in InAs and In0.5Ga0.5As. PMID- 9982539 TI - First-principles study of the structure and energetics of neutral divacancies in silicon. PMID- 9982540 TI - Nonlocality and many-body effects in the optical properties of semiconductors. PMID- 9982541 TI - Verification of EL2 electronic absorption effect on charge transfer in semi insulating GaAs. PMID- 9982543 TI - Vibrational spectra of defects in silicon: An orbital radii approach. PMID- 9982542 TI - Optical processes related to arsenic vacancies in semi-insulating GaAs studied by positron spectroscopy. PMID- 9982544 TI - Electron velocity overshoot and nonequilibrium phonons in a GaAs-based p-i-n nanostructure studied by transient subpicosecond Raman spectroscopy. PMID- 9982546 TI - Photoluminescence study of the one-dimensional material ZrS3 and its solid solution Zr1-xHfxS3. PMID- 9982545 TI - Nonequilibrium phonon dynamics and electron distribution functions in InP and InAs. PMID- 9982547 TI - Laser-power dependence of absorption changes in Ge-doped SiO2 glass induced by a KrF excimer laser. PMID- 9982549 TI - Thermodynamic properties of c-Si derived by quantum path-integral Monte Carlo simulations. PMID- 9982548 TI - Measurements and analysis of the gap and local modes of BGa impurities in GaP. PMID- 9982550 TI - Coherent optical generation of nonequilibrium electrons studied via band-to acceptor luminescence in GaAs. PMID- 9982551 TI - Nonequilibrium phonon effects on the transient high-field transport regime in InP. PMID- 9982552 TI - Resonance pattern in electronic transmittance for two identical coupled random dimer chains under different lead configurations. PMID- 9982553 TI - Submonolayer structure of an abrupt Al/GaAs{001}-(2 x 4) interface. PMID- 9982554 TI - Formation of GaAs/AlAs(001) interfaces studied by scanning tunneling microscopy. PMID- 9982556 TI - Electronic, structural, and dynamical properties of the GaAs(110):Ge surface. PMID- 9982555 TI - Calculated Schwoebel barriers on Si(111) steps using an empirical potential. PMID- 9982557 TI - Band structure of holes in p-type delta -doping quantum wells and superlattices. PMID- 9982559 TI - Many-electron ground states in anisotropic parabolic quantum dots. PMID- 9982558 TI - Correlations, compressibility, and capacitance in double-quantum-well systems in the quantum Hall regime. PMID- 9982560 TI - Electron interference in a T-shaped quantum transistor based on Schottky-gate technology. PMID- 9982562 TI - Parametric conductance correlation for irregularly shaped quantum dots. PMID- 9982561 TI - Coulomb scattering lifetime of a two-dimensional electron gas. PMID- 9982564 TI - Scattering-matrix method for the tight-binding model of heterostructure electronic states. PMID- 9982563 TI - Anisotropic hole subband states and interband optical absorption in PMID- 9982565 TI - Enhancement of spin-dependent hole delocalization in degenerate asymmetric double quantum wells. PMID- 9982567 TI - Spin-ordering and magnon collective modes for two-dimensional electron lattices in strong magnetic fields. PMID- 9982566 TI - Chaotic dynamics of electric-field domains in periodically driven superlattices. PMID- 9982568 TI - Coherent resonant tunneling in ac fields. PMID- 9982569 TI - Influence of typical environments on quantum processes. PMID- 9982570 TI - Ballistic transmission of composite fermions in a side-gated crossed-wire junction. PMID- 9982571 TI - Second virial coefficient for contact-interacting anyons. PMID- 9982572 TI - Electron-electron scattering in linear transport in two-dimensional systems. PMID- 9982573 TI - Shot noise in the presence of phonon-assisted transport through quasiballistic nanowires. PMID- 9982574 TI - Interaction of excitons with a generalized Morse surface potential: p polarization geometry of the incident light at a semiconductor surface. PMID- 9982575 TI - One- and two-photon-dressed effects in infrared-coupled quantum wells. PMID- 9982576 TI - Dynamic changes in reflectance anisotropy from the Si(001) surface during gas source molecular-beam epitaxy. PMID- 9982578 TI - Defect-pool model and the hydrogen density of states in hydrogenated amorphous silicon. PMID- 9982577 TI - Pressure dependence of the photoluminescence of strained (001) and (111) InxGa1 xAs quantum wells. PMID- 9982580 TI - Electric-field-induced Mott metal-insulator transition. PMID- 9982579 TI - Energy spectrum of a Bloch electron on a highly anisotropic two-dimensional lattice in a strong magnetic field: The analogy with the Wannier-Stark ladder. PMID- 9982581 TI - Charged Skyrmions: A condensate of spin excitons in a two-dimensional electron gas. PMID- 9982582 TI - Collective behavior in the single-electron charging regime through classical molecular dynamics. PMID- 9982583 TI - Intradonor absorption spectra under external fields in quantum wells. PMID- 9982585 TI - Resistance resonances from a magnetic impurity in an electron waveguide. PMID- 9982584 TI - Effects of spin-orbit coupling on persistent current and electronic thermal capacity in one-dimensional conducting rings. PMID- 9982586 TI - Analytical theory of NEXAFS from diatomic molecules. PMID- 9982588 TI - In situ characterization of epitaxially grown thin layers. PMID- 9982587 TI - Quasi-two-dimensional quantum states of H2 in stage-2 Rb-intercalated graphite. PMID- 9982589 TI - Final-state scattering in angle-resolved ultraviolet photoemission from copper. PMID- 9982591 TI - Collective excitations of multishell carbon microstructures: Multishell fullerenes and coaxial nanotubes. PMID- 9982590 TI - In situ sequential STM imaging of structural changes resulting from the electrodissolution of silver crystal surfaces in aqueous perchloric acid: The roughening kinetics. PMID- 9982592 TI - Ion-beam mixing of Ag/Fe and In/Fe layers studied by hyperfine techniques. PMID- 9982593 TI - Structures of Fe3O4 (111) surfaces observed by scanning tunneling microscopy. PMID- 9982594 TI - Unexpected adsorption sites for potassium and rubidium adsorption on Ag(111). PMID- 9982595 TI - Capture zones and scaling in homogeneous thin-film growth. PMID- 9982596 TI - Conductance in disordered nanowires: Forward and backscattering. PMID- 9982597 TI - Theoretical study of adsorption of Cu, Ag, and Au on the NaCl(100) surface. PMID- 9982598 TI - Surface polaritons on metallic wire gratings studied via power losses. PMID- 9982599 TI - Detailed theoretical photoelectron angular distributions for LiF(100). PMID- 9982600 TI - Infrared reflectance studies on a Fe3O4 film deposited on a MgO substrate: Observation of the substrate longitudinal optic phonon resonance peak in the film geometry. PMID- 9982601 TI - Coupling, resonance transmission, and tunneling of surface-plasmon polaritons through metallic gratings of finite length. PMID- 9982602 TI - Local density of unoccupied states in ion-beam-mixed Pd-Ag alloys. PMID- 9982603 TI - Analysis of angle-resolved photoemission data of PbS (001) surfaces within the direct-transition model. PMID- 9982605 TI - Electronic structure of silver overlayers on W(100). PMID- 9982604 TI - Adlayer core-level shifts of admetal monolayers on transition-metal substrates and their relation to the surface chemical reactivity. PMID- 9982606 TI - Surface-plasmon mode on a random rough metal surface: Enhanced backscattering and localization. PMID- 9982607 TI - Resonant photoelectron spectroscopy on NiO. PMID- 9982608 TI - Energy shift of the Cu L3M4,5M4,5 Auger line excited by proton impact on Cu(110): Enhanced electron correlations at the surface. PMID- 9982609 TI - Magnetism and structure of small clusters: An exact treatment of electron correlations. PMID- 9982611 TI - Locking of the tunneling distance in STM-type junctions: The influence of surface acoustic waves. PMID- 9982610 TI - Competition between vibrational excitation and dissociation in collisions of H2 with Cu(100). PMID- 9982612 TI - Erratum: Coulomb interaction and persistent currents in ensembles of mesoscopic metal rings PMID- 9982613 TI - Erratum: Currents in the compressible and incompressible regions of the two dimensional electron gas PMID- 9982614 TI - Erratum: Magnetic energy bands of carbon nanotubes PMID- 9982615 TI - Erratum: Current-density-functional theory of quantum dots in a magnetic field PMID- 9982616 TI - Erratum: Green's-function calculations of valence photoemission spectra of Pd2CO and Pt2CO PMID- 9982618 TI - Erratum: Universal equilibrium currents in the quantum Hall fluid PMID- 9982617 TI - Erratum: Experimental determination of the quasiparticle charge and the energy gap in the fractional quantum Hall effect PMID- 9982619 TI - Optical and transport studies of Ni(dmit)2-based organic conductors. PMID- 9982621 TI - Influence of quasiparticle damping on magnetic stability. PMID- 9982620 TI - Improved treatment of retarded self-energy calculations in perturbation theory. PMID- 9982622 TI - Further orbital-free kinetic-energy functionals for ab initio molecular dynamics. PMID- 9982623 TI - Electronic structure of Li12Si7. PMID- 9982624 TI - Electronic structure and bonding in skutterudite-type phosphides. PMID- 9982626 TI - Electronic structure of Pt in polyyne. PMID- 9982625 TI - Electronic origins of ordering in multicomponent metallic alloys: Application to the Cu-Ni-Zn system. PMID- 9982627 TI - Superhyperfine structures of the relaxed excited state of the F centers in KCl observed by zero-frequency optical detection of electron-nuclear double resonance. PMID- 9982629 TI - Alternative equations of motion for dynamical simulated annealing of the density functional. PMID- 9982628 TI - Dispersive photoconductivity in the layered perovskite Nd2Ti3O9. PMID- 9982630 TI - Nonlinear optical susceptibilities of conjugated polymers: Damping, resonances, and scaling laws. PMID- 9982632 TI - Spin-gap phase of strongly correlated fermions. PMID- 9982631 TI - O 1s near-edge x-ray absorption of La2-xSrxNiO4+ delta : Holes, polarons, and excitons. PMID- 9982633 TI - Ab initio pseudopotential study of Fe, Co, and Ni employing the spin-polarized LAPW approach. PMID- 9982634 TI - Conducting state of polyaniline films: Dependence on moisture. PMID- 9982635 TI - Semiconductor band switching by charging a small grain with a single electron. PMID- 9982636 TI - X-ray diffraction examinations of EL2-like defect metastability in low temperature gallium arsenide. PMID- 9982637 TI - Terms linear in k in the band structure of wurtzite-type semiconductors. PMID- 9982638 TI - Coexistence of the DX center with nonmetastable states of the donor impurity in Si-doped AlxGa1-xAs: Effects on the low-temperature electron mobility. PMID- 9982639 TI - Raman spectroscopy of Cd1-xCrxS. PMID- 9982640 TI - Fe-based semimagnetic semiconductors with two anions. PMID- 9982641 TI - Radiation ionization energy in a-Si:H. PMID- 9982642 TI - Calculation of second-order optical response in semiconductors. PMID- 9982643 TI - Theory of photoinduced charge transfer in a molecularly doped conjugated polymer. PMID- 9982644 TI - Suppression of Si-Ge interfacial vibration mode in the Raman spectrum of a Si6Ge4 superlattice. PMID- 9982645 TI - Multiple phase structures of NiSi2 on Si(001): An atomic view. PMID- 9982647 TI - Efficient exciton energy transfer between widely separated quantum wells at low temperatures. PMID- 9982646 TI - Ion-energy effects in silicon ion-beam epitaxy. PMID- 9982648 TI - Theory of exciton recombination from the magnetically induced Wigner crystal. PMID- 9982649 TI - Modified Lanczos procedure for Wannier-Stark resonances in solids. PMID- 9982650 TI - Structures of low-lying states of a four-electron system in a quantum dot. PMID- 9982651 TI - Hydrostatic-pressure determination of tensile-strained GaxIn1-xP-(AlyGa1 y)0.52In0.48P quantum-well band offsets. PMID- 9982652 TI - Excitonic molecules and stimulated emission in a ZnSe single quantum well. PMID- 9982653 TI - Charging and infrared spectroscopy of self-assembled quantum dots in a magnetic field. PMID- 9982654 TI - Compressibility of the electron gas: Analytical results for width effects within the Hartree-Fock approximation. PMID- 9982655 TI - Influence of growth direction and strain conditions on the band lineup at GaSb/InSb and InAs/InSb interfaces. PMID- 9982656 TI - Theory for the cyclotron resonance of holes in strained asymmetric Ge-SiGe quantum wells. PMID- 9982657 TI - Screening effects on the confined and interface polarons in cylindrical quantum wires. PMID- 9982658 TI - Eckardt frame theory of interacting electrons in quantum dots. PMID- 9982659 TI - Optimization of resonant intersubband nonlinear optical susceptibility in semiconductor quantum wells: The coordinate transform approach. PMID- 9982660 TI - Charged steps on III-V compound semiconductor surfaces. PMID- 9982661 TI - Numerical study of localization in the two-state Landau level. PMID- 9982662 TI - Edge of the Laughlin droplet. PMID- 9982663 TI - Hydrostatic-pressure coefficient of the direct band-gap energy of AlxGa1-xAs for x=0-0.35. PMID- 9982664 TI - Microwave modulation of circularly polarized exciton photonluminescence in GaAs/AlAs multiple quantum wells. PMID- 9982665 TI - Resonance in the Fermi-edge singularity of one-dimensional systems. PMID- 9982666 TI - Theory of Si 2p core-level shifts at the Si(001)-SiO2 interface. PMID- 9982667 TI - Dissipative quantum transport in a quantum wire. PMID- 9982669 TI - Elasticity theory of straight dislocations in a multilayer. PMID- 9982668 TI - Heavy-hole-light-hole quantum beats in nonlinear transmission spectroscopy. PMID- 9982670 TI - Spin-flip Raman-scattering studies of compensating donor centers in nitrogen doped zinc selenide grown by molecular-beam epitaxy. PMID- 9982672 TI - Cavity-polariton photoluminescence in semiconductor microcavities: Experimental evidence. PMID- 9982671 TI - Effects of the finite band width in a two-dimensional electron gas: The renormalization constant and the effective mass. PMID- 9982673 TI - Ground-state description of quasi-one-dimensional polarons with arbitrary electron-phonon coupling strength. PMID- 9982674 TI - Spatially resolved Raman scattering from hot acoustic and optic plasmons. PMID- 9982675 TI - Vacancylike structure of the DX center in Te-doped AlxGa1-xAs. PMID- 9982677 TI - Interference of current distortion patterns and magnetoresistance anisotropy in a composite with periodic microstructure. PMID- 9982676 TI - Linearized quantum transport equations: ac conductance of a quantum wire with an electron-phonon interaction. PMID- 9982678 TI - Optical properties of magnetic sawtooth superlattices. PMID- 9982679 TI - Quasiclassical calculation of magnetoresistance oscillations of a two-dimensional electron gas in spatially periodic magnetic and electrostatic fields. PMID- 9982680 TI - Layer-KKR theory of negative-ion formation in adsorbed molecules. PMID- 9982682 TI - Scanning tunneling microscopy of the phase transition between H/Si(100)-(2 x 1) and H/Si(100)-(3 x 1). PMID- 9982681 TI - Moire pattern in scanning tunneling microscopy: Mechanism in observation of subsurface nanostructures. PMID- 9982683 TI - Structural and electronic properties of pentagon-heptagon pair defects in carbon nanotubes. PMID- 9982684 TI - Clear evidence for strain changes according to Co layer thickness in metastable Co/Pd(111) multilayers: An extended x-ray absorption fine structure study. PMID- 9982685 TI - Elastic field of a surface step: Atomistic simulations and anisotropic elastic theory. PMID- 9982686 TI - Roughening and melting of stepped aluminum surfaces. PMID- 9982687 TI - Simulations of low-temperature annealing of crystal surfaces. PMID- 9982688 TI - Heat-capacity study of butane on graphite. PMID- 9982689 TI - Growth of Cr on Cu(001) studied by scanning tunneling microscopy. PMID- 9982690 TI - Initial growth of Mg films on Ru(0001): An efficient approximation scheme for the LEED analysis of incommensurate structures. PMID- 9982691 TI - Enhanced epitaxial growth on substrates modified by ion sputtering: Ge on GaAs(110). PMID- 9982692 TI - Data evaluation technique for electron-tunneling spectroscopy. PMID- 9982693 TI - Thermal conductance and the Peltier coefficient of carbon nanotubes. PMID- 9982694 TI - Two-photon electron emission from smooth and rough metal films in the threshold region. PMID- 9982695 TI - Dissociation of polyatomic ions at surfaces: The influence of mechanical and electronic energy transfer. PMID- 9982696 TI - Focused inelastic resonances in the scattering of He atoms from NaCl(001). PMID- 9982697 TI - Magnetostrictive model for the determination of the energy diagram of dysprosium epitaxial films. PMID- 9982698 TI - General potential-energy function for H/Ni and dynamics calculations of surface diffusion, bulk diffusion, subsurface-to-surface transport, and absorption. PMID- 9982699 TI - Dynamical screening effects in surface ionization: Application to C60. PMID- 9982700 TI - Band-theoretical description of the magneto-optical spectra of UAsSe. PMID- 9982701 TI - Self-consistent order-N density-functional calculations for very large systems. PMID- 9982702 TI - Density-matrix renormalization-group method in momentum space. PMID- 9982703 TI - Strain-induced reduction of 1/f noise of sliding charge-density waves. PMID- 9982704 TI - Effects of weak disorder on two coupled Hubbard chains. PMID- 9982705 TI - Chemical trends in band offsets of Zn- and Mn-based II-VI superlattices: d-level pinning and offset compression. PMID- 9982706 TI - Magnetic relaxation studied by transient reflectivity in Cd1-xMnxTe. PMID- 9982707 TI - Picosecond-luminescence study of exciton formation dynamics in CdSe. PMID- 9982708 TI - Vacuum Rabi coupling enhancement and Zeeman splitting in semiconductor quantum microcavity structures in a high magnetic field. PMID- 9982709 TI - Local-field effect in the second-harmonic-generation spectra of Si surfaces. PMID- 9982710 TI - Theory of GaN(101-bar0) and (112-bar0) surfaces. PMID- 9982712 TI - Temperature dependence of the photoluminescence of ZnSe/ZnS quantum-dot structures. PMID- 9982711 TI - Nucleation and growth of Fe on GaAs(001)-(2 x 4) studied by scanning tunneling microscopy. PMID- 9982713 TI - Size dependence of electron-LO-phonon coupling in semiconductor nanocrystals. PMID- 9982714 TI - Experimental study of the effect of quantum-well structures on the thermoelectric figure of merit. PMID- 9982715 TI - Optical properties of strained InP quantum dots in Ga0.5In0.5P studied by space charge techniques. PMID- 9982716 TI - Nonlinear optical effects in strain-induced laterally ordered (InP)2/(GaP)2 quantum wires. PMID- 9982717 TI - Subband renormalization in dense electron-hole plasmas in In0.53Ga0.47As/InP quantum wires. PMID- 9982718 TI - Nature of optical transitions in self-organized InAs/GaAs quantum dots. PMID- 9982719 TI - Magnetoplasma excitations in electron rings. PMID- 9982720 TI - Weakly correlated exciton pair states in large quantum dots. PMID- 9982721 TI - Dimensional crossover and confinement-induced optical anisotropy in GaAs T-shaped quantum wires. PMID- 9982722 TI - Zero-Hall-resistance state in a semimetallic InAs/GaSb superlattice. PMID- 9982724 TI - Analysis of the x-ray diffuse scattering in C60 from microscopic models. PMID- 9982723 TI - Electron scattering by steps in a vicinal heterointerface. PMID- 9982726 TI - Cluster diffusion by evaporation-condensation. PMID- 9982725 TI - Theory of a scanning tunneling microscope with a two-protrusion tip. PMID- 9982727 TI - Spin-polarized photoelectrons excited by circularly polarized radiation from a nonmagnetic solid. PMID- 9982728 TI - Suppression of the magnetocrystalline bulk anisotropy in thin epitaxial Co(110) films on Cu(110). PMID- 9982730 TI - Lattice relaxation at vacancy aggregates in diamond. PMID- 9982729 TI - Effect of photoinduced defect sites on the photoluminescence of sodium cryptand sodide. PMID- 9982731 TI - Evidence for domain-type dynamics in the ergodic phase of the PbMg1/3Nb2/3O3 relaxor ferroelectric. PMID- 9982732 TI - Validity of generalized scattering equations and corresponding inelastic-cross section expressions for comprehensive electron diffraction conditions. PMID- 9982733 TI - Expanded-volume phases of silicon: Zeolites without oxygen. PMID- 9982734 TI - Stretched-exponential relaxation modeled without invoking statistical distributions. PMID- 9982735 TI - Two- and three-dimensional polarons with extended coherent states. PMID- 9982736 TI - Inhomogeneous quantum diffusion. PMID- 9982738 TI - Improved formulation of the effective-potential Monte Carlo method. PMID- 9982737 TI - Late stages of phase separation in Al1-xSix solid solutions. PMID- 9982739 TI - Zero-temperature spin-wave spectrum of the critical two-layer S=1/2 antiferromagnet. PMID- 9982740 TI - Canted coupling of buried magnetic multilayers. PMID- 9982741 TI - Instability of planar vortices in layered ferromagnets with nonmagnetic impurities. PMID- 9982742 TI - Hall effect in the quadrupolar Kondo ground state. PMID- 9982743 TI - Suppression of the superconducting transition temperature Tc around x~0.115 in La2-xSrxCuO4. PMID- 9982744 TI - Exchange integral and the charge gap of the linear-chain cuprate Sr2CuO3. PMID- 9982745 TI - Nonmonotonic superconducting transitions in mesoscopic Al structures induced by radio-frequency radiation. PMID- 9982746 TI - Dynamically induced disorder in the vortex lattice of 2H-NbSe2. PMID- 9982747 TI - Occurrence of superconductivity in Ca- and Sr-doped PrSr2Cu2.7Mo0.3O7- delta. PMID- 9982748 TI - Effect of impurities on the transport properties in the Van Hove scenario. PMID- 9982750 TI - Thermodynamics and critical fields of YBa2(Cu1-xNix)3O7- delta from a d-wave model of superconductivity. PMID- 9982749 TI - Dependence of the flux-creep time scale on sample size for melt-textured YBa2Cu3O7 by ac-susceptibility measurements. PMID- 9982752 TI - Change of absorption spectra in type-Ib diamond with heavy neutron irradiation. PMID- 9982751 TI - Theoretical analysis of laser-induced effects in silver halides. PMID- 9982753 TI - Depth profiles of interstitial halogen defects in high-energy ion-bombarded RbI by micro-Raman spectroscopy. PMID- 9982755 TI - Molecular-dynamics study of displacement cascades in Cu-Au solid solutions. PMID- 9982754 TI - Pressure-dependent Knight shift in Na and Cs metal. PMID- 9982756 TI - Light-induced kinetic effects in solids. PMID- 9982758 TI - High-pressure ultrasonic study of the Cr-0.3 at.% Ru single-crystal alloy in the commensurate spin-density-wave phase and through the Neel point. PMID- 9982757 TI - Reversible phase transition between the metastable phases of tetracyanoethylene under high pressure. PMID- 9982759 TI - Heat capacity and the orientational transition in solid C60. PMID- 9982760 TI - Lattice dynamics and hyperfine interactions in ZnO and ZnSe at high external pressures. PMID- 9982762 TI - X-ray-absorption spectroscopy of Nd3+-exchanged beta -alumina crystal. PMID- 9982761 TI - Surface effects and size effects on ferroelectrics with a first-order phase transition. PMID- 9982763 TI - Hydrogen in porous Vycor glass. PMID- 9982764 TI - Antiphase boundaries, inversion, and ferroelastic domains in the striped-type superstructure of gamma -brass Cu-Al alloys. PMID- 9982765 TI - Low-frequency vibrations in a model glass. PMID- 9982767 TI - Influence of one-fold-coordinated atoms on mechanical properties of covalent networks. PMID- 9982766 TI - Irreversible frustrated spinodal decomposition in simultaneous interpenetrating polymer networks: Small-angle x-ray scattering. PMID- 9982768 TI - Diffusion and magnetic relaxation in model porous media. PMID- 9982769 TI - Electronic transport in quasicrystals: An approach to scattering with fractional multicomponent Fermi surfaces. PMID- 9982770 TI - Relaxational and vibrational dynamics in the glass-transition range of a strong glass former B2O3. PMID- 9982771 TI - Quasiharmonic periodic traveling-wave solutions in anharmonic potentials. PMID- 9982772 TI - Interaction of discrete breathers with electrons in nonlinear lattices. PMID- 9982773 TI - Non-Markovian effects on quantum beats. PMID- 9982774 TI - Numerical evaluation of frequency-moment sum rules for dynamical structure factors. PMID- 9982775 TI - Magnetic structure and anisotropy of Ga- and Al-substituted LaCo5 and YCo5 intermetallics. PMID- 9982776 TI - Dynamic finite-size effect in the classical spin van der Waals model. PMID- 9982778 TI - Critical behavior of the two-dimensional step model. PMID- 9982777 TI - Magnetic anisotropy of epitaxial Co/Mn superlattices: An angular-dependent ferromagnetic resonance study. PMID- 9982779 TI - Universal correction to scaling amplitude ratios for inhomogeneous ferromagnets with continuous symmetry. PMID- 9982780 TI - Spinons, solitons, and magnons in one-dimensional Heisenberg-Ising antiferromagnets. PMID- 9982781 TI - Phase diagram of CeCu2(Si1-xGex)2. PMID- 9982783 TI - Knight shift, electric-field gradient, and electronic state in the spin-Peierls compound CuGeO3: 63,65Cu NMR in a single crystal. PMID- 9982782 TI - Self-consistent Gaussian approximation for classical spin systems: Thermodynamics. PMID- 9982784 TI - Magnetic exchange-coupling effects in asymmetric trilayer structures of MBE-grown Co/Cr/Fe. PMID- 9982785 TI - Magnetic-circular-dichroism study of the valence states of perpendicularly magnetized Ni(001) films. PMID- 9982786 TI - Effect of host paramagnetic ions on the Gd3+ EPR linewidth in diluted Van-Vleck paramagnets TmxLu1-xPO4 and HoxY1-xVO4 and EPR spectra of Er3+ in HoxY1-xVO4. PMID- 9982787 TI - Dimerized ground state and magnetic excitations in CaCuGe2O6. PMID- 9982788 TI - Athermal magnetization avalanches and domain states in the site-diluted metamagnet FexMg1-xCl2. PMID- 9982789 TI - Ferromagnetic interactions in nanostructured systems with two different Curie temperatures. PMID- 9982790 TI - Magnetic anisotropies and general on-site Coulomb interactions in the cuprates. PMID- 9982791 TI - Jordan-Wigner approach to the spin excitation spectrum in the Heisenberg antiferromagnet. PMID- 9982793 TI - Macroscopic theory of giant magnetoresistance in magnetic granular metals. PMID- 9982792 TI - Physical properties of the Ce(Ru1-xFex)2Ge2 series. PMID- 9982794 TI - Magnetic and transport dc properties of inductive Josephson-junction arrays. PMID- 9982796 TI - Luttinger-liquid behavior and superconducting correlations in t-J ladders. PMID- 9982795 TI - One-hole motion in the two-dimensional frustrated t-J model. PMID- 9982797 TI - Variational approach to the Hubbard model in a C60 cluster. PMID- 9982798 TI - Optical properties of single-crystal Sr2CuO2Cl2. PMID- 9982799 TI - Accommodation of vortices to columnar defects: Evidence for large entropic reduction of vortex localization. PMID- 9982800 TI - Superconducting properties of fractal Nb/Cu multilayers. PMID- 9982801 TI - Helical instability of a magnetic flux line in a current-carrying superconducting film. PMID- 9982802 TI - Dynamic interaction of mesoscopic Josephson junctions with quantized electromagnetic fields. PMID- 9982804 TI - Exact diagonalization plus renormalization-group theory: Accurate method for a one-dimensional superfluid-insulator-transition study. PMID- 9982803 TI - Magnetic-field dependence of conductance in microjunctions employing nonhomogeneous superconducting electrodes. PMID- 9982805 TI - Determination of the valence of Pr in (Eu1.5-xPrxCe0.5)Sr2Cu2NbO10 superconducting compounds by electron-energy-loss spectroscopy. PMID- 9982806 TI - Optical properties of superconducting Bi2Sr2CaCu2O8. PMID- 9982807 TI - Raman-active phonons in Bi2Sr2Ca1-xYxCu2O8+d (x=0-1): Effects of hole filling and internal pressure induced by Y doping for Ca, and implications for phonon assignments. PMID- 9982808 TI - Magnetization jumps and irreversibility in Bi2Sr2CaCu2O8. PMID- 9982809 TI - Coherent versus incoherent transport in layered doped Mott insulators. PMID- 9982810 TI - Temperature and doping dependence of the penetration depth in Bi2Sr2CaCu2O8+ delta. PMID- 9982811 TI - Effect of pressure on Tc and the "intrinsic" Tc of cuprates. PMID- 9982813 TI - High-field and low-temperature magnetization and flux creep in untwinned YBa2Cu3O7-x. PMID- 9982812 TI - Monte Carlo study of vortex fluctuations in vortex-line phases. PMID- 9982814 TI - Vortex avalanches at one thousandth the superconducting transition temperature. PMID- 9982815 TI - Pressure effect on Tc for (Yb1-xPrx)Ba2Cu3O7. PMID- 9982816 TI - Nonlinear magneto-optical response of s- and d-wave superconductors. PMID- 9982817 TI - Raman electronic continuum in a dx2-y2 superconductor: Inelastic scattering. PMID- 9982818 TI - Comment on "Crystallization kinetics" PMID- 9982819 TI - Comment on "Adiabatic theory for the bipolaron" PMID- 9982820 TI - Erratum: Peierls-Nabarro model of dislocations in silicon with generalized stacking-fault restoring forces PMID- 9982821 TI - Erratum: Test of the Peierls-Nabarro model for dislocations in silicon PMID- 9982822 TI - Erratum: Calculation of the strain-induced shifts in the infrared-absorption peaks of cubic boron nitride PMID- 9982823 TI - Erratum: Mixed-state thermoelectric and thermomagnetic effects of a Bi2Sr2CaCu2O8+ delta single crystal PMID- 9982824 TI - Monte Carlo study of a compressible Ising antiferromagnet on a triangular lattice. PMID- 9982825 TI - High-resolution electron microscopy and modeling of homologous series in nonstoichiometric lead-niobium oxides. PMID- 9982827 TI - Dilute and dense systems of random copolymers in the equilibrium state. PMID- 9982826 TI - Vibronic theory of the stability and hysteresis in bistable mixed-valence molecular salts. PMID- 9982828 TI - Structural anisotropy in amorphous Fe-Tb thin films. PMID- 9982829 TI - Structural transitions in octagonal, decagonal, and dodecagonal quasicrystals. PMID- 9982830 TI - Magnetic-field effects on localization in a fractal lattice. PMID- 9982831 TI - Local icosahedral structures in binary-alloy clusters from molecular-dynamics simulation. PMID- 9982832 TI - Diffusion of Brownian particles trapped between two walls: Theory and dynamic light-scattering measurements. PMID- 9982834 TI - Molecular dynamics with quantum forces: Vibrational spectra of localized systems. PMID- 9982833 TI - Quantum lattice motion and optical absorption in conjugated polymers: Adiabatic theory. PMID- 9982835 TI - Thermodynamic properties of the C60 fullerite at high temperatures: Calculations taking into account the intramolecular degrees of freedom and strong anharmonicity of the lattice vibrations. PMID- 9982837 TI - Low-frequency dielectric susceptibility of Li+-doped KCl. PMID- 9982836 TI - Interplay of orbital degeneracy and superconductivity in a molecular conductor. PMID- 9982838 TI - Harmonic behavior of metallic glasses up to the metastable melt. PMID- 9982839 TI - First-principles molecular-dynamics simulations for neutral p-chloranil and its radical anion. PMID- 9982840 TI - Anharmonic calculations of the optical-phonon lifetime for crystals with the diamond structure. PMID- 9982841 TI - Surface and confined optical phonons in CdSxSe1-x nanoparticles in a glass matrix. PMID- 9982842 TI - Weak-coupling phase diagram of the two-chain Hubbard model. PMID- 9982843 TI - Transverse-random-field mixed Ising model with arbitrary spins. PMID- 9982844 TI - Resistivity saturation in substitutionally disordered gamma -Fe80-xNixCr20 (14 <~ x <~ 30) alloys. PMID- 9982846 TI - Exchange stiffness, magnetization, and spin waves in cubic and hexagonal phases of cobalt. PMID- 9982845 TI - Effect of Y substitution in La-Ca-Mn-O perovskites showing giant magnetoresistance. PMID- 9982847 TI - Nonlinear self-channeling and beam shaping of magnetostatic waves in ferromagnetic films. PMID- 9982849 TI - Phase transitions of the bilayered spin-S Heisenberg model. PMID- 9982848 TI - Magnetic linear dichroism in spin-resolved Fe 2p photoemission. PMID- 9982850 TI - Observation of a dimerized state in the S=1/2 quasi-one-dimensional antiferromagnet Sr14Cu24O41. PMID- 9982851 TI - Bilayer Heisenberg model studied by the Schwinger-boson Gutzwiller-projection method. PMID- 9982852 TI - Observation of an anomalous quasi-one-dimensional behavior in Na2Ru4O9- delta single crystals. PMID- 9982853 TI - Phase transition of the dissipative one-dimensional Ising model. PMID- 9982854 TI - Calculation of the exchange coupling between two magnetized layers embedded in a metal. PMID- 9982855 TI - Eddy currents and spin excitations in conducting ferromagnetic films. PMID- 9982857 TI - Multiphonon excitations in boson quantum films. PMID- 9982856 TI - Excitations in a thin liquid 4He film from inelastic neutron scattering. PMID- 9982858 TI - Superconducting wires and fractional flux. PMID- 9982859 TI - Nonuniform superconductivity due to the orbital magnetic effect in a d-wave superconductor in a magnetic field. PMID- 9982860 TI - Electronic-structure effects in the suppression of superconductivity in hydrogenated Zr2Rh. PMID- 9982862 TI - Flux creep and flux jumping. PMID- 9982861 TI - Manifestation of quasiparticle branch imbalance in resistive measurements of mesoscopic superconductors. PMID- 9982863 TI - Doping and high-pressure study on Lu(Ni1-xAx)BC with A=Cu and V. PMID- 9982864 TI - Butterfly magnetization in YBa2Cu3-xFexO7-y: Correlation with the microstructure and the macrostructure. PMID- 9982865 TI - Temperature dependence of the magnetic-flux penetration into disk-shaped YBa2Cu3O7- delta thin films. PMID- 9982866 TI - Synchronization and phase locking in two-dimensional arrays of Josephson junctions. PMID- 9982867 TI - E1g model of superconducting UPt3. PMID- 9982868 TI - Phase locking between Fiske and flux-flow modes in coupled sine-Gordon systems. PMID- 9982869 TI - Toulouse points and non-Fermi-liquid states in the mixed-valence regime of the generalized Anderson model. PMID- 9982870 TI - Influence of phase composition on the reentrant superconducting properties of Tm2Fe3Si5. PMID- 9982871 TI - Quantization of superflow circulation and magnetic flux with a tunable offset. PMID- 9982872 TI - Optical conductivity of a layered superconductor. PMID- 9982873 TI - Modulation structure in Bi2Sr1.8La0.2Cu1-xMxOy (M=Fe, Co, Ni, and Zn). PMID- 9982874 TI - Effect of HgI2 intercalation on Bi2Sr2CaCu2Oy: Interlayer coupling effect. PMID- 9982876 TI - Interaction between localized and conduction-electron spins in the high-Tc superconductor Gd:EuBa2Cu3O6+x. PMID- 9982875 TI - Percolative vortex motion in high-temperature superconductors. PMID- 9982877 TI - Photoexcited carrier relaxation and localization in Bi2Sr2Ca1-yYyCu2O8 and YBa2Cu3O7- delta : A study by femtosecond time-resolved spectroscopy. PMID- 9982878 TI - Paramagnetic Meissner effect in high-temperature superconductors: Experiments and interpretation. PMID- 9982879 TI - Universal Tc suppression by in-plane defects in high-temperature superconductors: Implications for pairing symmetry. PMID- 9982880 TI - Effect of oxygen defects on transport properties and Tc of YBa2Cu3O6+x: Displacement energy for plane and chain oxygen and implications for irradiation induced resistivity and Tc suppression. PMID- 9982881 TI - Scaling of the specific heat and magnetization of YBa2Cu3O7 in magnetic fields up to 7 T. PMID- 9982882 TI - Ginzburg-Landau equations for a d-wave superconductor with nonmagnetic impurities. PMID- 9982883 TI - Dependence of the critical temperature on atomic structure in orthorhombic YBa2Cu3Ox. PMID- 9982884 TI - Influence of Pr doping and oxygen deficiency on the scattering behavior of YBa2Cu3O7 thin films. PMID- 9982885 TI - Dielectric polarization noise through the glass transition. PMID- 9982886 TI - Lateral transport in disordered layered media. PMID- 9982887 TI - Defect formation in SiO2:GeO2 glasses studied by irradiation with excimer laser light. PMID- 9982888 TI - Photoinduced generation and reorientation of linear dichroism in AsSe glassy films. PMID- 9982889 TI - Theory of tunneling magnetoresistance in granular magnetic films. PMID- 9982891 TI - Magnetic circular x-ray-dichroism study of Co/Pt(111). PMID- 9982890 TI - Resonant two-magnon Raman scattering in cuprate antiferromagnetic insulators. PMID- 9982892 TI - Extraordinary Hall effect in giant magnetoresistive Fe/Cr multilayers: The role of interface scattering. PMID- 9982893 TI - Competition between the singlet-spin liquid state and the magnetic ground state in a two-chain spin-1/2 antiferromagnetic ladder compound LaCuO2.5: A 63Cu NMR study. PMID- 9982894 TI - High-resolution photoemission study of CeRu2: The dual character of 4f electrons. PMID- 9982895 TI - Vortex pinning by disordered columnar defects in large Josephson junctions. PMID- 9982896 TI - Microscopic theory of vortex pinning: Impurity terms in the Ginzburg-Landau free energy. PMID- 9982897 TI - Theory of the Josephson effect in d-wave superconductors. PMID- 9982898 TI - Manifestations of the pseudogap in the boson-fermion model for Bose-Einstein condensation-driven superconductivity. PMID- 9982900 TI - Three-dimensional gap structure in layered high-temperature superconductors. PMID- 9982899 TI - Interlayer tunneling in a non-Fermi-liquid metal. PMID- 9982901 TI - Interplanar coupling, induced superconductivity, and van Hove singularity in high Tc cuprates. PMID- 9982902 TI - Pressure dependence of thermopower in YBa2Cu3O6.96 and YBa2Cu4O8. PMID- 9982903 TI - Confinement of spin and charge in high-temperature superconductors. PMID- 9982905 TI - Photodissociation dynamics of gas-phase C60 probed by optical emission spectroscopy. PMID- 9982904 TI - Decay of the self-trapped exciton and Frenkel-pair formation in NaF: An ab initio study. PMID- 9982906 TI - Effect of pressure on the optical-absorption edges of CsGeBr3 and CsGeCl3. PMID- 9982907 TI - Band-structure parameters by genetic algorithm. PMID- 9982908 TI - Peierls instability of a one-dimensional quantum liquid. PMID- 9982909 TI - Representation of the t-J model using decoupled spin and charge variables. PMID- 9982911 TI - Nb4N3: Polymorphism in crystalline niobium nitrides. PMID- 9982910 TI - Kondo hole behavior in Ce0.97 La0.03Pd3. PMID- 9982913 TI - Electron paramagnetic resonance of a Au-Au pair in heat-treated silicon. PMID- 9982912 TI - Ammonia as an active doping source gas of hydrogenated amorphous germanium films. PMID- 9982914 TI - Finite-size effects in the exciton-phonon coupled system. PMID- 9982916 TI - Intraband inversion due to ultrashort carrier lifetimes in proton-bombarded InP. PMID- 9982915 TI - Superexchange and spin-glass formation in semimagnetic semiconductors. PMID- 9982917 TI - Real-space investigation of initial growth process of hydrogenated amorphous silicon on a graphite substrate. PMID- 9982918 TI - Atomic geometry and bonding on the GaAs(001)- beta 2(2 x 4) surface from ab initio pseudopotential calculations. PMID- 9982919 TI - Shakeup processes in the recombination spectra of negatively charged excitons. PMID- 9982920 TI - Localization and mesoscopic persistent current in a disordered metal ring. PMID- 9982921 TI - Gor'kov and Eliashberg linear-response theory: Rigorous derivation and limits of applicability. PMID- 9982923 TI - Electronic structure of a buried NiSi2 or CoSi2 layer in bulk Si. PMID- 9982924 TI - Magic numbers and optical-absorption spectrum in vertically coupled quantum dots in the fractional quantum Hall regime. PMID- 9982922 TI - Adatom-adatom and adatom-surface interactions: Islands and chains of Cl on GaAs(110). PMID- 9982925 TI - Magnetoplasmons in a ring-shaped two-dimensional electron gas. PMID- 9982926 TI - Coulomb charging at large conduction. PMID- 9982927 TI - Influence of energy level alignment on tunneling between coupled quantum dots. PMID- 9982929 TI - L-band recombination in InxGa1-xP/In0.5Al0.5P multiple quantum wells. PMID- 9982930 TI - Femtosecond study of exciton tunneling in (Zn,Cd)Se/ZnSe asymmetric double quantum wells. PMID- 9982928 TI - Size-dependent two-photon excitation spectroscopy of CdSe nanocrystals. PMID- 9982931 TI - Comparison of bond character in hydrocarbons and fullerenes. PMID- 9982932 TI - Interlayer interactions in LiC6: Compressibility and thermal expansion. PMID- 9982934 TI - Low-temperature reconstruction pathway to the Si(111)( sqrt(3) x sqrt(3) )R30 degrees-Ag interface. PMID- 9982933 TI - Heat capacity of thin films of 3He adsorbed on a heterogeneous substrate. PMID- 9982935 TI - Enhanced photon stimulated ion-desorption yields from chemisorbed molecules through bond-selective core-electron excitation. PMID- 9982936 TI - Surface-enhanced Raman scattering at elevated temperatures. PMID- 9982937 TI - Anisotropic second-harmonic generation of electric quadrupolar origin in copper phthalocyanine films epitaxially grown by molecular-beam epitaxy. PMID- 9982938 TI - Weighted-density approximation in metals and semiconductors. PMID- 9982939 TI - Photon focusing, internal diffraction, and surface states in periodic dielectric structures. PMID- 9982940 TI - Electronic structure and chemical-bonding mechanism of Cu3N, Cui3NPd, and related Cu(I) compounds. PMID- 9982941 TI - Bond-order potentials: Theory and implementation. PMID- 9982942 TI - Structure of solid-state systems from embedded-cluster calculations: A divide-and conquer approach. PMID- 9982943 TI - Extended Huckel tight-binding study of the effect of pressure and uniaxial stress on the electronic structure of alpha -(BEDT-TTF)2KHg(SCN)4 and kappa -(BEDT TTF)2Cu(NCS)2. PMID- 9982944 TI - Linear-scaling tight binding from a truncated-moment approach. PMID- 9982945 TI - Orbital and spin orderings in YVO3 and LaVO3 in the generalized gradient approximation. PMID- 9982946 TI - Nonmetal-metal transition in metal-molten-salt solutions. PMID- 9982947 TI - Nonrelativistic fermions coupled to transverse gauge fields: The single-particle Green's function in arbitrary dimensions. PMID- 9982948 TI - Electronic properties of the narrow-band material alpha -RuCl3. PMID- 9982949 TI - Microwave absorption in insulating dielectric ionic crystals including the role of point defects. PMID- 9982950 TI - Theory of nonlinear optical response of excitons in solid C60. PMID- 9982952 TI - Finite-size effects and unsaturated ferromagnetism of two-component Hubbard rings in a strong magnetic field: Exact results. PMID- 9982951 TI - Resonant magnetoabsorption of millimeter-wave radiation in the quasi-two dimensional organic metals alpha -(BEDT-TTF)2MHg(SCN)4 (M=K,Tl). PMID- 9982953 TI - Five-level k PMID- 9982954 TI - Energy states of Be in GaAs. PMID- 9982955 TI - Hydrogen passivation of shallow donors S, Se, and Te in GaAs. PMID- 9982956 TI - Possibility of a metastable state for a transition-metal impurity in semiconductor. PMID- 9982957 TI - Generalized Monte Carlo approach for the study of the coherent ultrafast carrier dynamics in photoexcited semiconductors. PMID- 9982958 TI - Screening and energy loss by hot carriers in semiconductors. PMID- 9982959 TI - Host-isotope fine structure of local and gap modes of substitutional impurities in zinc-blende and wurtzite II-VI semiconductors. PMID- 9982960 TI - Local and gap modes of substitutional 3d transition-metal ions in zinc-blende and wurtzite II-VI semiconductors. PMID- 9982962 TI - Low-temperature transport properties of NdBiPt. PMID- 9982961 TI - Effect of negative differential conductivity in a driven diffusive lattice gas. PMID- 9982963 TI - Scanning tunneling microscopy study of Si growth on a Si(111) sqrt(3) x sqrt(3) B surface. PMID- 9982964 TI - Dynamic growth steps of n x n dimer-adatom-stacking-fault domains on the quenched Si(111) surface. PMID- 9982966 TI - Landau levels and persistent currents in nonuniform magnetic fields. PMID- 9982965 TI - Interband transitions in AlxGa1-xAs/AlAs quantum-well structures. PMID- 9982967 TI - Quasi-two-dimensional electron gas: Exchange and correlation energies. PMID- 9982968 TI - Impurity center in a single quantum well in the presence of a strong magnetic field. PMID- 9982969 TI - Observation of interface states by high-resolution electron-energy-loss spectroscopy in metal-GaAs(110) junctions. PMID- 9982970 TI - Coulomb blockade in a quantum dot coupled strongly to a lead. PMID- 9982971 TI - Self-consistent calculation of resonant tunneling in asymmetric double barriers in a magnetic field. PMID- 9982972 TI - Statistics of skyrmions in quantum Hall systems. PMID- 9982973 TI - Intrasubband excitations of composite fermions in a quantum wire. PMID- 9982974 TI - Radiative recombination in cylindrical GaAs-(Ga,Al)As quantum-well wires under quasistationary excitation conditions. PMID- 9982975 TI - Quantum transport theory of Weiss oscillations quenching of a two-dimensional electron gas in a strong periodic potential. PMID- 9982976 TI - Raman scattering in single-variant spontaneously ordered GaInP2. PMID- 9982977 TI - Photoluminescence due to positively charged excitons in undoped GaAs/AlxGa1-xAs quantum wells. PMID- 9982978 TI - Spectroscopic investigations of photoinduced changes of the spatial distribution of charge carriers in modulation-doped quantum-well structures. PMID- 9982979 TI - Classical continuum theory of the dipole-forbidden collective excitations in quantum strips. PMID- 9982980 TI - Random matrix theory and mesoscopic fluctuations. PMID- 9982981 TI - Finite-difference method for the calculation of low-energy positron diffraction. PMID- 9982982 TI - X-ray photoelectron-diffraction analysis of oxygen chemisorption on the GaAs(110) surface. PMID- 9982983 TI - Oxygen-related defects in Si studied by variable-energy positron annihilation spectroscopy. PMID- 9982984 TI - Theory of polariton photoluminescence in arbitrary semiconductor microcavity structures. PMID- 9982985 TI - Length dependence of quantized conductance in ballistic constrictions fabricated on InAs/AlSb quantum wells. PMID- 9982986 TI - Electronic transport in nanoscale contacts with rough boundaries. PMID- 9982987 TI - Quantum conductance fluctuations in the large-size-scale regime. PMID- 9982988 TI - Supercurrent states in one-dimensional finite-size rings. PMID- 9982989 TI - Empirical bond polarizability model for fullerenes. PMID- 9982990 TI - Adsorption geometry of OH adsorbed at F centers on a NaCl(100) surface. PMID- 9982991 TI - First-principles calculations of beta -SiC(001) surfaces. PMID- 9982993 TI - Anisotropic optical response of the diamond (111)-2 x 1 surface. PMID- 9982992 TI - Persistent quantum-size effect in aluminum films up to twelve atoms thick. PMID- 9982995 TI - Formation of C60 dimers: A theoretical study of electronic structure and optical absorption. PMID- 9982994 TI - Dynamics of surface alloying: Determination of diffusion barriers from photoelectron spectra. PMID- 9982996 TI - Computation of electrostatic fields in low-symmetry systems: Application to STM configurations. PMID- 9982998 TI - Comment on "Hopping transport in a magnetic field: Kadanoff-Baym-Keldysh approach and magnetoconductivity" PMID- 9982997 TI - Disordered flat phase and phase diagram for restricted solid-on-solid models of fcc (110) surfaces. PMID- 9982999 TI - Reply to "Comment on 'Hopping transport in a magnetic field: Kadanoff-Baym Keldysh approach and magnetoconductivity' " PMID- 9983000 TI - Erratum: Dominant density parameters and local pseudopotentials for simple metals PMID- 9983001 TI - Erratum: In-plane dispersion relations of InAs/AlSb/GaSb/AlSb/InAs interband resonant-tunneling diodes PMID- 9983002 TI - Observation of liquid carbon on diamond films under pulsed IR and UV laser irradiation. PMID- 9983003 TI - Mean escape depth of signal photoelectrons ejected from solids by polarized x rays. PMID- 9983004 TI - High-pressure melting curves of alkali halides. PMID- 9983005 TI - Self-similarity of dielectric relaxation and conductivity in cross-linking systems. PMID- 9983006 TI - Effect of pressure on the atomic volume of Zn, Cd, and Hg up to 75 GPa. PMID- 9983008 TI - Interference between Judd-Ofelt and Wybourne-Downer mechanisms in the 5D0-7FJ (J=2,4) transitions of Sm2+ in solids. PMID- 9983007 TI - Hydrogen ordering in superstoichiometric rare-earth hydrides for a system with an energy-constants ratio p=V2/V1<1: LaH2+x. PMID- 9983009 TI - Phenomenological model of elastic distortions near the spin-Peierls transition in CuGeO3. PMID- 9983011 TI - Collective dynamics in glasses and its relation to the low-temperature anomalies. PMID- 9983012 TI - Evidence of strong short-range order in (Fe0.2Co0.8)75SixB25-x amorphous alloys from EXAFS spectroscopy. PMID- 9983010 TI - Electric-field gradients at 111Cd in delafossite oxides ABO2 (A=Ag, Cu; B=Al, Cr, Fe, In, Nd, Y). PMID- 9983013 TI - Effective-medium theory for the electric-field dependence of the hopping conductivity of disordered solids. PMID- 9983014 TI - Structure and thermodynamic properties of liquid transition metals: An embedded atom-method approach. PMID- 9983015 TI - Failure of fiber bundles with local load sharing. PMID- 9983016 TI - Landau damping and lifting of vibrational degeneracy in metallic potassium fulleride. PMID- 9983017 TI - Muonium localization in solid krypton. PMID- 9983018 TI - Monte Carlo method for obtaining the ground-state properties of quantum spin systems. PMID- 9983019 TI - Exchange interactions and magnetism of Co2+ in Zn1-xCoxTe. PMID- 9983020 TI - Origin of the second length scale found above TN in UO2. PMID- 9983021 TI - UxM1-xPt3 (M=Y, Lu, In) compounds with the AuCu3 structure. PMID- 9983023 TI - Quantum version of a spherical model: Crossover from quantum to classical critical behavior. PMID- 9983022 TI - Cationic and magnetic order in LiNiO2- and NiO-type Li-Ni mixed oxides. PMID- 9983024 TI - Universality class of non-Fermi-liquid behavior in mixed-valence systems. PMID- 9983026 TI - Local-field distribution in systems with dipolar interparticle interaction. PMID- 9983025 TI - High-resolution magnetic x-ray diffraction from neodymium. PMID- 9983028 TI - Quantum dynamical calculations on the magnetization reversal in clusters of spin 1/2 particles: Resonant coherent quantum tunneling. PMID- 9983027 TI - Thermodynamic properties of one-dimensional spin-1 antiferromagnetic Heisenberg chains: Green's-function approach. PMID- 9983029 TI - Collective excitations in itinerant spiral magnets. PMID- 9983030 TI - Low-temperature magnetic structure of UNiGe. PMID- 9983032 TI - Magnetic excitations and effects of magnetic fields on the spin-Peierls transition in CuGeO3. PMID- 9983031 TI - Connection between giant magnetoresistance and structure in molecular-beam epitaxy and sputtered Fe/Cr superlattices. PMID- 9983033 TI - Weak ferromagnetism in the low-temperature tetragonal phase of the cuprates. PMID- 9983034 TI - Nonlocal Coulomb interactions and the magnetic anisotropies in the low temperature phases of the cuprates. PMID- 9983035 TI - Paramagnetic Meissner effect in Nb. PMID- 9983036 TI - Nature of the magnetic order in superconducting and nonsuperconducting HoNi2 xCoxB2C. PMID- 9983038 TI - Diagrammatic derivation of Bose condensate fractions. PMID- 9983037 TI - Response of niobium-based superconducting tunnel junctions in the soft-x-ray region 0.15-6.5 keV. PMID- 9983039 TI - Phase diagram of a model of correlated hopping of electrons in a lattice of Berry molecules. PMID- 9983041 TI - Tilt instabilities and multiple coexisting vortex orientations in flux-line liquids. PMID- 9983040 TI - Raman-scattering and weak-ferromagnetism studies in Eu2CuO4. PMID- 9983042 TI - Spin-phonon coupling in the single-layer extended t-J model. PMID- 9983043 TI - Oxygen dependence of the transport properties of Nd1.78Ce0.22CuO4+/- delta. PMID- 9983044 TI - Inelastic-neutron-scattering study of antiferromagnetic fluctuations in YBa2Cu3O6.97. PMID- 9983045 TI - Large-shift Raman scattering features in superconducting YBa2Cu3O6+x. PMID- 9983046 TI - c-axis negative magnetoresistance and fluctuation conductivity of Bi2Sr2CaCu2Ox single crystals. PMID- 9983047 TI - Dissipative and Hall quantum creep in YBa2Cu3O7- delta thin films. PMID- 9983048 TI - Nonlinear effective barriers for flux diffusion and critical current density of HgBa2Ca2Cu3Ox based upon ac susceptibility measurement. PMID- 9983049 TI - Scaling of the thermoelectric power in a wide temperature range in Bi2Sr2Ca1 xNdxCu2Oy (x=0-0.5): Experiment and interpretation. PMID- 9983050 TI - Quasiparticle structure and coherent propagation in the t-Jz-Jperp model. PMID- 9983051 TI - Oxidation state of Ce in Pb2Sr2Ce1-xCaxCu3O8. PMID- 9983053 TI - Nonadiabatic superconductivity: The role of van Hove singularities. PMID- 9983052 TI - Grain-boundary-induced magneto-far-infrared resonances in superconducting YBa2Cu3O7- delta thin films. PMID- 9983054 TI - Origin of magnetic coupling in La2CuO4. PMID- 9983055 TI - Comment on "Thermal hysteresis effects in the ferroelectric-ferroelastic phase transition in PMID- 9983056 TI - Dual alkali-metal-ion channel structures in poly(p-phenylenevinylene). PMID- 9983057 TI - Enhanced local moment formation in a chiral Luttinger liquid. PMID- 9983058 TI - Itinerant and local-moment antiferromagnetism in V2-yO3: A NMR study. PMID- 9983059 TI - Size dependence of Kondo scattering in point contacts: Fe impurities in Cu. PMID- 9983061 TI - Phase transition in the three-dimensional +/-J Ising spin glass. PMID- 9983060 TI - Giant-magnetoresistance anomaly associated with a magnetization process in UFe4Al8. PMID- 9983062 TI - Local moments coupled to a strongly correlated electron chain. PMID- 9983063 TI - Impurity state in the Haldane gap for an S=1 Heisenberg antiferromagnetic chain with bond doping. PMID- 9983064 TI - NMR investigation of the electronic structure of the RbC60 polymer phase. PMID- 9983066 TI - Spatiotemporal dynamics of domain-wall solitons in the fully frustrated Josephson junction ladder arrays. PMID- 9983065 TI - Thermodynamical properties of an antiferromagnetic Heisenberg spin system on a fractal lattice of dimension between one and two. PMID- 9983067 TI - Screening in Josephson-junction ladders. PMID- 9983069 TI - Critical and noncritical behavior of the Kosterlitz-Thouless-Berezinskii transition. PMID- 9983068 TI - Muon-spin-rotation studies of HoNi2B2C. PMID- 9983070 TI - Transition temperature and a spatial dependence of the superconducting gap for multilayer high-temperature superconductors. PMID- 9983072 TI - Effects of intrabilayer coupling on the magnetic properties of YBa2Cu3O6. PMID- 9983071 TI - Theory of the c-axis penetration depth in the cuprates. PMID- 9983074 TI - Phase separation and softening of the O2,3 in-phase mode in the YBa2Cu3Ox superconductors. PMID- 9983073 TI - Scaling in spin susceptibility of high-Tc cuprates: A model with nondegenerate fermions. PMID- 9983075 TI - Percolation transition of the vortex lattice and c-axis resistivity in high temperature superconductors. PMID- 9983077 TI - Formation of satellite bands in the ionization spectra of extended systems. PMID- 9983076 TI - Molecular first hyperpolarizability of push-pull polyenes: Relationship between electronic and vibrational contribution by a two-state model. PMID- 9983078 TI - Memory loss and Auger processes in a many-body theory of charge transfer. PMID- 9983079 TI - Magneto-optical study of paraexcitons in NaI. PMID- 9983080 TI - Positron states in noble liquids: Affinity, effective mass, and mobility. PMID- 9983081 TI - Investigation of hole-doped insulating La1-xSrxCrO3 by soft-x-ray absorption spectroscopy. PMID- 9983082 TI - Quantum interference from sums over closed paths for electrons on a three dimensional lattice in a magnetic field: Total energy, magnetic moment, and orbital susceptibility. PMID- 9983083 TI - F-center formation by Br K-hole Auger decay in KBr. PMID- 9983085 TI - Pressure-dependent properties of SiC polytypes. PMID- 9983084 TI - Compton profile of vanadium carbide and vanadium nitride. PMID- 9983086 TI - Band bending within inhomogeneously doped semiconductors with multilevel impurities. I. Theory. PMID- 9983087 TI - Band bending within inhomogeneously doped semiconductors with multilevel impurities. II. Examples. PMID- 9983088 TI - Electronic structure of the N-V center in diamond: Experiments. PMID- 9983089 TI - Electronic structure of the N-V center in diamond: Theory. PMID- 9983090 TI - Nonlinear optics of conjugated polymers: A coupled exciton-phonon-gas approach. PMID- 9983091 TI - Second-harmonic generation resonant to the 1S orthoexciton level of cuprous oxide. PMID- 9983092 TI - Coupled solitons in resonant Raman interaction of intense polaritons. PMID- 9983093 TI - Electron-screening effects on the self-trapping of polarons. PMID- 9983094 TI - Ga-bound excitons in 3C-, 4H-, and 6H-SiC. PMID- 9983095 TI - Wannier excitons and Franz-Keldysh effect of polydiacetylene chains diluted in their single crystal monomer matrix. PMID- 9983096 TI - Photoluminescence spectrum and dynamics in oxidized silicon nanocrystals: A nanoscopic disorder system. PMID- 9983097 TI - Saddle-point configurations for self-interstitial migration in silicon. PMID- 9983098 TI - Optically detected magnetic resonance study of efficient two-layer conjugated polymer light-emitting diodes. PMID- 9983099 TI - Growth of Si on different GaAs surfaces: A comparative study. PMID- 9983100 TI - In situ spectroscopic ellipsometry of GaAs(001) surface reconstructions. PMID- 9983102 TI - Segregation and diffusion on semiconductor surfaces. PMID- 9983101 TI - Adatom diffusion on Ge(111) and the corresponding activation energy barrier. PMID- 9983103 TI - Edge excitations of paired fractional quantum Hall states. PMID- 9983105 TI - Transverse magnetoresistance of GaAs/AlxGa1-xAs heterojunctions in the presence of parallel magnetic fields. PMID- 9983104 TI - Quantum-well states in metallic-thin-film overlayers. PMID- 9983106 TI - Cesium-induced electronic states and space-charge-layer formation in Cs/InSb(110) interface. PMID- 9983107 TI - Electronic states in antidot lattices: Scattering-matrix formalism. PMID- 9983108 TI - Resonant magnetotunneling spectroscopy of p-type-well interband tunneling diodes. PMID- 9983109 TI - Hole magnetoplasmons in quantum dots. PMID- 9983111 TI - Formula for Coulomb effect on the nonlinear optical responses in quantum wells. PMID- 9983110 TI - Quantum interference effects in a strongly fluctuating magnetic field. PMID- 9983112 TI - Magnetic-field-induced modulation of intersubband scattering in a double-barrier resonant-tunneling structure. PMID- 9983113 TI - Exact propagators for a two-dimensional electron in quadratic potentials and a transverse magnetic field. PMID- 9983114 TI - Optics of multiple quantum wells uniaxially stressed along the growth axis. PMID- 9983115 TI - Raman-scattering probe of anharmonic effects due to temperature and compositional disorder in III-V binary and ternary alloy semiconductors. PMID- 9983116 TI - Background charge noise in metallic single-electron tunneling devices. PMID- 9983118 TI - Stochastic treatment of the dynamics of excitons and excitonic molecules in CuCl nanocrystals. PMID- 9983117 TI - Exciton ionization induced by an electric field in a strongly coupled GaAs/AlxGa1 xAs superlattice. PMID- 9983120 TI - Effect of composite nonmagnetic spacer layer on exchange coupling in magnetic superlattices. PMID- 9983119 TI - Si(001)/B surface reconstruction. PMID- 9983121 TI - Thermal ionization of excitons in V-shaped quantum wires. PMID- 9983122 TI - Geometric structure of Be(101-bar0). PMID- 9983124 TI - Structure of the diamond (111) surface: Single-dangling-bond versus triple dangling-bond face. PMID- 9983123 TI - Adsorption and temperature-dependent decomposition of SO2 on Cu(100) and Cu(111): A fast and high-resolution core-level spectroscopy study. PMID- 9983125 TI - First-principles study of the H-induced reconstruction of W(110). PMID- 9983126 TI - Relaxation of hcp(0001) surfaces: A chemical view. PMID- 9983127 TI - Initial stages of metal encapsulation during epitaxial growth studied by STM: Rh/Ag(100). PMID- 9983129 TI - Pattern-formation study of macroscopic dense branching morphology in Bi0.69Al0.27Mn/SiO films. PMID- 9983128 TI - Green's-tensor approach in the theory of the surface or interface vibrational contribution to thermodynamic properties of solids. PMID- 9983130 TI - Quantum delocalization of H on Pd(110): A vibrational study. PMID- 9983131 TI - First-principles calculation of the longitudinal phonon in the surface-normal direction of a zirconium(0001) slab: Localization mode at the subsurface. PMID- 9983133 TI - High-resolution core-level study of 6H-SiC(0001). PMID- 9983132 TI - Nonuniversality in models of epitaxial growth. PMID- 9983134 TI - Electronic structure of 6H-SiC(0001). PMID- 9983135 TI - Experimental study of the valence-band region of Mg-Pd and Ba-Pd interfaces with and without hydrogen and of Mg and Ba hydrides. PMID- 9983137 TI - Curvature-induced bonding changes in carbon nanotubes investigated by electron energy-loss spectrometry. PMID- 9983136 TI - Integrity of quantum-well resonances in metallic overlayers. PMID- 9983138 TI - Dynamics of low-energy-electron stimulated desorption of metastable particles from N2 condensed on Xe and Kr films. PMID- 9983139 TI - Energy loss of MeV protons specularly reflected from metal surfaces. PMID- 9983140 TI - Catalytic oxidation of the GaAs(110) surface promoted by a Cs overlayer. PMID- 9983142 TI - Theoretical investigation of the C60 infrared spectrum. PMID- 9983141 TI - Energy minimization using the classical density distribution: Application to sodium chloride clusters. PMID- 9983143 TI - Dimerization and fusion of C60 molecules caused by molecular collision. PMID- 9983144 TI - Structure of kinks for a complex ground state. PMID- 9983145 TI - Adhesion in NiAl-Cr from first principles. PMID- 9983146 TI - Lattice dynamics of ultrathin layers of KBr grown epitaxially on RbCl(001). PMID- 9983148 TI - Theoretical study of the electromigration wind force for adatom migration at metal surfaces. PMID- 9983147 TI - Strain and confined resonances in ultrathin alkali-metal films. PMID- 9983149 TI - Fluorescence decay in aperiodic Frenkel lattices. PMID- 9983150 TI - Effects of lithium intercalation on the electronic properties of FePS3 single crystals. PMID- 9983151 TI - Iron clusters supported in a zeolite matrix: Comparison of different magnetic characterizations. PMID- 9983152 TI - NMR study of the anomalous metallic state below the CDW transition temperature in Rb3Cu8S6: A possibility of self-organized spinless solitons. PMID- 9983154 TI - Kinetics of surfactant-mediated epitaxy of III-V semiconductors. PMID- 9983153 TI - Binding energies of hydrogen to the Si(111) 7 x 7 surface studied by statistical scanning tunneling microscopy. PMID- 9983155 TI - Equivalence of the transmission-eigenvalue density in supersymmetric and scaling theories of disordered wires without time-reversal symmetry. PMID- 9983156 TI - Tunneling conductance of Luttinger liquids: Resonances. PMID- 9983157 TI - Structural and spectroscopic investigations of CdS/HgS/CdS quantum-dot quantum wells. PMID- 9983158 TI - Magnetic switching and thermal enhancement of quantum transport through nanowires. PMID- 9983160 TI - Electron confinement in a-Si:H and an effective-mass theorem for amorphous semiconductors. PMID- 9983159 TI - Symmetry breaking of the admittance of a classical two-dimensional electron system in a magnetic field. PMID- 9983161 TI - Scanning-tunneling-microscopy study of InP(001) surfaces prepared by UHV decapping of metal-organic vapor-phase-epitaxy-grown samples. PMID- 9983162 TI - Magneto-optical evidence of the percolation nature of the metal-insulator transition in the two-dimensional electron system. PMID- 9983163 TI - Electronic structure and optical properties of coupled quantum dots. PMID- 9983164 TI - Electron weak localization in disordered films. PMID- 9983165 TI - Extending the high-frequency limit of a single-electron transistor by on-chip impedance transformation. PMID- 9983166 TI - Paired states in the even integer quantum Hall effect. PMID- 9983167 TI - Low-frequency anomalies and scaling of the dynamic conductivity in the quantum Hall effect. PMID- 9983168 TI - Electron drift reversal caused by remaining holes in semiconductor superlattices due to effective-mass filtering. PMID- 9983169 TI - Raman efficiency in a planar microcavity. PMID- 9983171 TI - Ultrafast photoexcited cyclotron emission: Contributions from real and virtual excitations. PMID- 9983170 TI - Large and irregular shift of photoluminescence excitation spectra observed in photochemically etched porous silicon. PMID- 9983172 TI - Prediction of a pure-carbon planar covalent metal. PMID- 9983173 TI - Confinement mechanism for strong temperature dependence of the interlayer exchange coupling in Co/Cu(001). PMID- 9983174 TI - Quantum-well-driven magnetism in thin films. PMID- 9983176 TI - Structural properties of bulk copper: Pseudopotential plane-wave-basis study. PMID- 9983175 TI - Resonant enhancement of second-harmonic generation of electric quadrupole origin in phthalocyanine films. PMID- 9983177 TI - Comparative study of nonlinear localized modes of diatomic chains with two types of quartic nonlinearity. PMID- 9983179 TI - Evidence for a local lattice distortion in Ca-doped LaMnO3. PMID- 9983178 TI - Relaxation jumps of strong vibration. PMID- 9983180 TI - Renormalized effective-medium theory for weakly nonlinear composites. PMID- 9983181 TI - 1H NMR study of the dimensional crossover in C10H21NH3Cl. PMID- 9983182 TI - ESR study of potassium-doped aligned carbon nanotubes. PMID- 9983184 TI - Density-matrix renormalization-group study of the spin-1/2 XXZ antiferromagnet on the Bethe lattice. PMID- 9983183 TI - Method for solving integrable A2 spin chains combining different representations. PMID- 9983185 TI - Electronic contributions to spin-wave characteristics in antiferromagnetic metals. PMID- 9983186 TI - Amorphous iron revisited: An ab initio study. PMID- 9983187 TI - Exchange coupling in single-crystalline spinel-structure (Mn,Zn)Fe2O4/CoFe2O4 bilayers. PMID- 9983188 TI - Double-exchange interaction in electron-doped CaMnO3- delta perovskites. PMID- 9983189 TI - Perpendicular giant magnetoresistance of Co/Cu multilayers on grooved substrates: Systematic analysis of the temperature dependence of spin-dependent scattering. PMID- 9983190 TI - Proton NMR in a TDAE-C60 single crystal. PMID- 9983191 TI - Effect of annealing on the giant Hall effect. PMID- 9983192 TI - Superconductivity in a spin liquid: A one-dimensional example. PMID- 9983193 TI - Superconducting-critical-temperature oscillations in Nb/CuMn multilayers. PMID- 9983194 TI - Anisotropy and two length scales in the magnetic critical scattering in the heavy fermion superconductor UPd2Al3. PMID- 9983196 TI - Indication for an antiferromagnetic exchange interaction in high-Tc superconductors. PMID- 9983195 TI - Normal-state Nernst effect of a high-critical-temperature superconductor. PMID- 9983197 TI - High-resolution angle-resolved photoemission spectroscopy of the momentum dependence of the superconducting gap in Bi2Sr2CaCu2O8. PMID- 9983198 TI - Multiatom covalent bonding and the formation enthalpy of Na2K. PMID- 9983199 TI - First-principles theory of iron up to earth-core pressures: Structural, vibrational, and elastic properties. PMID- 9983200 TI - Lattice-dynamical study of the structure and elasticity of dodecasil-3C at elevated temperatures. PMID- 9983201 TI - Higher-order elasticity of cubic metals in the embedded-atom method. PMID- 9983202 TI - Pressure-induced distortions of Pb(NO3)2 isomorphs. PMID- 9983203 TI - Ferroelastic phase transitions in the K3Na(SeO4)2 glaserit-type crystal. PMID- 9983205 TI - Molecular-dynamics prediction of structural anomalies in ferroelectric and dielectric BaTiO3-SrTiO3-CaTiO3 solid solutions. PMID- 9983204 TI - ac-field-dependent structure-property relationships in La-modified lead zirconate titanate: Induced relaxor behavior and domain breakdown in soft ferroelectrics. PMID- 9983207 TI - Secondary-electron and negative-ion emission from Al: Effect of oxygen coverage. PMID- 9983206 TI - Diffraction of atoms from stepped surfaces: A semiclassical chaotic S-matrix study. PMID- 9983208 TI - Localized fluoride diffusion and defect equilibrium in CaF2:Eu3+ using site selective spectroscopy and high-pressure techniques. PMID- 9983209 TI - Structural scattering of phonons in quasicrystals. PMID- 9983210 TI - Microstructural evolution of source rocks during hydrocarbon generation: A small angle-scattering study. PMID- 9983211 TI - Lattice dynamics of BC2N. PMID- 9983213 TI - Phonon localization in one-dimensional quasiperiodic chains. PMID- 9983212 TI - Orientational defects on a hydrogen-bonded chain. PMID- 9983214 TI - Voltage distribution in a two-component random system. PMID- 9983215 TI - Solid C76: NMR studies of molecular dynamics. PMID- 9983216 TI - Theoretical studies of carrier transport in HgI2. PMID- 9983217 TI - Determination of a distribution of relaxation frequencies based on experimental relaxational data. PMID- 9983218 TI - Matrix mean-field theory for the paramagnetic susceptibility of disordered magnets. PMID- 9983220 TI - Crossover from two- to three-dimensional critical behavior for nearly antiferromagnetic itinerant electrons. PMID- 9983219 TI - High-temperature-series study of the spin-1/2 Heisenberg ferromagnet. PMID- 9983222 TI - Calculated spin polarization and magnetic dichroism of photoelectron diffraction spectra for magnetite below the Verwey temperature. PMID- 9983221 TI - Total spin and antiferromagnetic correlation in the Kondo model. PMID- 9983223 TI - Hyperfine fields at the Ba site in the antiferromagnet YBa2Cu3O6.05. PMID- 9983224 TI - Monoclinic microdomains and clustering in the colossal magnetoresistance manganites Pr0.7Ca0.25Sr0.05MnO3 and Pr0.75Sr0.25MnO3. PMID- 9983226 TI - Thermal variation of the relaxation time of the magnetic moment of gamma -Fe2O3 nanoparticles with interparticle interactions of various strengths. PMID- 9983225 TI - Magnetism and structural distortion in the La0.7Sr0.3MnO3 metallic ferromagnet. PMID- 9983227 TI - Oscillatory total spin in ferromagnet/metal(or insulator)/ferromagnet sandwich structures. PMID- 9983229 TI - ESR in conducting polymers: Oxygen-induced contribution to the linewidth. PMID- 9983228 TI - Thermopower of single-crystal Nd1-x(Sr,Pb)xMnO3- delta. PMID- 9983231 TI - Pattern dynamics of parametrically excited spin waves near the instability threshold. PMID- 9983230 TI - ESR studies on the Haldane material Ni(C3H10N2)2NO2ClO4: Polarization analysis and frequency-field diagram. PMID- 9983232 TI - Ordered arrangement of proton pairs in the PrNiInH1.29 system. PMID- 9983233 TI - Accuracy of the density-matrix renormalization-group method. PMID- 9983234 TI - Experimental observation of guided polarized neutrons in magnetic-thin-film waveguides. PMID- 9983235 TI - Quantum critical behavior of disordered itinerant ferromagnets. PMID- 9983236 TI - Short-distance behavior of the energy density near surfaces of critical systems. PMID- 9983237 TI - Rapid oscillations in the organic conductor (TMTSF)2ClO4. PMID- 9983238 TI - Magneto-oscillations in the high-magnetic-field state of (TMTSF)2ClO4. PMID- 9983240 TI - Magnetocrystalline anisotropy of YCo5 and related RECo5 compounds. PMID- 9983239 TI - Spin-flop phase and heavy fermion behavior in CePb3. PMID- 9983241 TI - Intrinsic electrical transport and magnetic properties of La0.67Ca0.33MnO3 and La0.67Sr0.33MnO3 MOCVD thin films and bulk material. PMID- 9983242 TI - First-order transition at TC in the orthomanganites. PMID- 9983243 TI - Spin susceptibility of boron carbides: Dissociation of singlet small bipolarons. PMID- 9983244 TI - X-ray-absorption sum rules in jj-coupled operators and ground-state moments of actinide ions. PMID- 9983246 TI - Surface vibrations of a 4He droplet and the universality of the dispersion relation. PMID- 9983245 TI - Electrical and magnetic properties of (Ca1-xAx)2MnO4 (A=La and Na). PMID- 9983247 TI - Collective modes in the electronic polarization of double-layer systems in the superconducting state. PMID- 9983249 TI - Interaction potential between vortex lines for uniaxial superconductors in the London approximation. PMID- 9983248 TI - Kinetic-equation approach to diffusive superconducting hybrid devices. PMID- 9983250 TI - Stability analysis of a two-dimensional uniaxial vortex glass. PMID- 9983251 TI - Quantized conductance in semiconductor-superconductor-junction quantum point contacts. PMID- 9983253 TI - Phase locking of Josephson junctions in a two-dimensional array. PMID- 9983252 TI - Charge-vortex duality in double-layered Josephson-junction arrays. PMID- 9983254 TI - Chaos and thermal noise in a Josephson junction coupled to a resonant tank. PMID- 9983256 TI - c-axis optical spectra and charge dynamics in La2-xSrxCuO4. PMID- 9983255 TI - Hubbard model with smooth boundary conditions. PMID- 9983257 TI - Experimental proof of the electronic charge-transfer mechanism in a YBa2Cu3O7-x based field-effect transistor. PMID- 9983258 TI - Explanation of the zero-bias anomaly in the tunneling characteristics of single crystal Bi2Sr2CaCu2O8 with intrinsic Josephson tunneling. PMID- 9983259 TI - Implications of dx2-y2 symmetry and faceting for the transport properties of grain boundaries in high-Tc superconductors. PMID- 9983260 TI - Determination of the onset of bulk pinning and the low-temperature irreversibility line in Bi2Sr2CaCu2O8+ delta. PMID- 9983261 TI - Collective mode and the c-axis critical current of a Josephson-coupled superconductor at high parallel magnetic fields. PMID- 9983262 TI - Influence of columnar defects on vortex dynamics in Bi2Sr2CaCu2O8 from out-of plane and flux transformer transport measurements. PMID- 9983263 TI - Crossover effects in the temperature dependence of the critical current in YBa2Cu3O7- delta. PMID- 9983264 TI - Pressure dependence of Tc in cuprate superconductors: Application to (CaxLa1 x)(Ba1.75-xLa0.25+x)Cu3Oy. PMID- 9983265 TI - Effect of 3d ion substitution in the RBa2Cu3-xMxO7 (R=Sm, Dy; M=Fe, Ni and Zn) system: Implications of R ion dependence and disorder. PMID- 9983266 TI - Crystal structures of Hg-Sr-Ca-Cu-O superconductors with enhanced flux pinning: Hg1-xRexSr2Can-1CunO2n+2+ delta (n=2,3; x PMID- 9983268 TI - Reply to "Comment on 'Infrared-reflectance spectra of heat-treated, sol-gel derived silica' " PMID- 9983267 TI - Comment on "Infrared-reflectance spectra of heat-treated, sol-gel-derived silica" PMID- 9983269 TI - Erratum: Superconducting correlations in the one-band Hubbard model with intermediate on-site and weak attractive intersite interactions PMID- 9983270 TI - Erratum: Antiferromagnetic excitations and van Hove singularities in YBa2Cu3O6+x PMID- 9983271 TI - Heat-diffusion central peak in the dielectric susceptibility of ferroelectric materials. PMID- 9983272 TI - Ion-beam mixing induced by atomic and cluster bombardment in the electronic stopping-power regime. PMID- 9983273 TI - Theory and numerical simulations of defect ordering in irradiated materials. PMID- 9983274 TI - Irradiation effects in Ag-Fe bilayers: Ion-beam mixing, recrystallization, and surface roughening. PMID- 9983275 TI - Vibrational properties of the layered semiconductor germanium sulfide under hydrostatic pressure: Theory and experiment. PMID- 9983276 TI - Characteristics of sensitized emission in laser crystals. PMID- 9983277 TI - Impact fragmentation of an ideal brittle crystal. PMID- 9983279 TI - Transport properties of waves in absorbing random media with microstructure. PMID- 9983278 TI - Second-order phase transition in crystals with long-range correlated quenched defects. PMID- 9983280 TI - Influence of heat treatment on the tunneling states in neutron-irradiated quartz. PMID- 9983281 TI - Spectral function for a conducting sheet containing circular inclusions. PMID- 9983282 TI - Hysteresis, avalanches, and disorder-induced critical scaling: A renormalization group approach. PMID- 9983283 TI - Curvature of acoustic slowness surface of anisotropic solids near symmetry axes. PMID- 9983284 TI - Nonlocal charge-transfer effects in the lattice dynamics of classical ionic crystals. PMID- 9983285 TI - Su-Schrieffer-Heeger model applied to chains of finite length. PMID- 9983287 TI - Low-frequency electrical noise in Ni: The effects of magnetic fluctuations. PMID- 9983286 TI - Time evolution of models described by a one-dimensional discrete nonlinear Schrodinger equation. PMID- 9983288 TI - Second-harmonic generation in magnetic colloids by orientation of the nanoparticles. PMID- 9983289 TI - Nonlinear self-localized magnetoelastic surface waves in antiferromagnetic media. PMID- 9983290 TI - Variational evidence for spin liquids in frustrated lattices. PMID- 9983291 TI - Spin-Peierls lattice fluctuations of pure and Si- and Zn-substituted CuGeO3. PMID- 9983292 TI - Relaxation and aging in Ising systems. PMID- 9983294 TI - Magnetic excitations in the sinusoidal spin phase of Er and Tm. PMID- 9983293 TI - Variation of f-electron localization in diluted US and UTe. PMID- 9983295 TI - Spin dynamics in the linear-chain S=1 antiferromagnet Ni(C3H10N2)2N3(ClO4). PMID- 9983297 TI - Domain-wall dynamics in aligned bound Sm2Fe17. PMID- 9983296 TI - Magnetic properties of Pm in NdNi. PMID- 9983298 TI - Giant magnetoresistance and microstructures in CoAg granular films fabricated using ion-beam co-sputtering technique. PMID- 9983299 TI - Magnetic and transport properties of NiFe/Ag and Co/NiFe/Co/Ag multilayers. PMID- 9983301 TI - Magneto-optic properties and ferromagnetism of (In,Mn)As/(In,Al)As/(Ga,Al)Sb heterostructures. PMID- 9983302 TI - Deuterium site occupancy in YDx by magic-angle-spinning NMR. PMID- 9983300 TI - Interlayer magnetic coupling: The torque method. PMID- 9983303 TI - Phase transitions in a spin-1 model with plaquette interaction on the square lattice. PMID- 9983304 TI - Local properties at Fe and Co impurities in Nb1-xMox alloys. PMID- 9983305 TI - Kondo effect in flux phases. PMID- 9983306 TI - Raman response in doped antiferromagnets. PMID- 9983307 TI - Giant magnetoresistive behavior near the metamagnetic transition in Ce(Fe0.93Ru0.07)2. PMID- 9983309 TI - Electrical and magnetic properties of Fe3-zAlzO4 (z<0.06). PMID- 9983308 TI - Size-dependence study of the spin glass CuMn (1%). PMID- 9983310 TI - Sharp photoemission spectra in the quantum antiferromagnet. PMID- 9983311 TI - Shadow wave function for liquid and solid 3He. PMID- 9983312 TI - ac properties of an anisotropic layered superconductor. PMID- 9983314 TI - Effect of gate voltage on critical current in controllable superconductor-normal metal-superconductor Josephson junctions. PMID- 9983313 TI - Electronic thermal conductivity and the Wiedemann-Franz law for unconventional superconductors. PMID- 9983315 TI - Evolution from BCS superconductivity to Bose condensation: Calculation of the zero-temperature phase coherence length. PMID- 9983316 TI - Topological defects in the random-field XY model and the pinned vortex lattice to vortex glass transition in type-II superconductors. PMID- 9983317 TI - Effect of diffusive boundaries on surface superconductivity in unconventional superconductors. PMID- 9983318 TI - Variational theory of elastic manifolds with correlated disorder and localization of interacting quantum particles. PMID- 9983319 TI - Superconductivity in amorphous Ta/Ge multilayers. PMID- 9983320 TI - Quantum-liquid regimes for spin chains coupled to phonons: Phonon density wave versus magnetic order. PMID- 9983322 TI - Low-temperature properties and specific anisotropy of pure anisotropically paired superconductors. PMID- 9983321 TI - Rare-earth ion size effect on resistivity, susceptibility, and superconductivity of RBa2Cu3-xZnxO7-y (R= Yb, Er, Y, Dy, Gd, Eu, Sm, and Nd). PMID- 9983323 TI - Vortex dynamics in YBa2Cu3O7- delta superconducting films: Experimental evidence for an instability in the vortex system at high current densities. PMID- 9983325 TI - ac magnetic hysteresis loops of Bi-Sr-Ca-Cu-O 110-K-phase superconductors and the effect of microstructural alteration. PMID- 9983324 TI - Thermal fluctuation effects on the magnetization above and below the superconducting transition in Bi2Sr2CaCu2O8 crystals in the weak magnetic field limit. PMID- 9983326 TI - Quasiparticle lifetimes and signatures of the superconductor order-parameter symmetry in phonon linewidths. PMID- 9983327 TI - Microwave-induced dc voltages in a YBa2Cu3O7- delta single crystal. PMID- 9983328 TI - Vortex structure and resistive transitions in high-Tc superconductors. PMID- 9983330 TI - Vortex structure in d-wave superconductors. PMID- 9983329 TI - Reversible magnetization and anisotropy in YBa2Cu4O8. PMID- 9983331 TI - Phase separation and valence instabilities in cuprate superconductors: Effective one-band-model approach. PMID- 9983332 TI - Structural phase transitions in bulk YBa2Cu3O6+x with x=0.35 and x=0.36. PMID- 9983334 TI - Lattice dynamics of RbC60 in its rotator, polymer, and dimer phase: A neutron scattering investigation. PMID- 9983333 TI - Fast in situ x-ray-diffraction studies of chemical reactions: A synchrotron view of the hydration of tricalcium aluminate. PMID- 9983335 TI - Calculation of the turnover in the vibrational frequencies of solid hydrogen at high pressures. PMID- 9983336 TI - Ferromagnetism-induced reentrant structural transition and phase diagram of the lightly doped insulator La1-xSrxMnO3 (x <~ 0.17). PMID- 9983337 TI - Temperature dependence of the spin-Peierls energy gap and anomalous line shapes in CuGeO3. PMID- 9983338 TI - Analytical results for a hole in an antiferromagnet. PMID- 9983339 TI - Neutron-scattering and susceptibility study of spin chains and spin ladders in (Sr0.8Ca0.2)14Cu24O41. PMID- 9983341 TI - Crossover from O(3) to O(4) behavior in weakly frustrated antiferromagnets. PMID- 9983340 TI - Muon-spin-relaxation studies of magnetic order in heavily doped La2-xSrxNiO4+ delta. PMID- 9983342 TI - Raman-scattering evidence for free spinons in the one-dimensional spin-1/2 chains of Sr2CuO3 and SrCuO2. PMID- 9983343 TI - Direct observation of particle-hole mixing in the superconducting state by angle resolved photoemission. PMID- 9983345 TI - High-precision penetration-depth measurement of YBa2Cu3O7- delta as a function of oxygen content. PMID- 9983344 TI - Direct observation of optical magnons in YBa2Cu3O6.2. PMID- 9983346 TI - Josephson plasma resonance in a single-layered cuprate Bi2(Sr,La)2CuOy. PMID- 9983347 TI - Doping dependence of the O 1s core-level photoemission in Bi-Sr-Ca-Cu-O superconductors. PMID- 9983348 TI - Analysis of the lock-in transition in Bi2Sr2CaCu2O8+ delta single crystals through microwave dissipation. PMID- 9983350 TI - Absence of a magnetic-field-induced metal-insulator transition in Kondo insulators. PMID- 9983349 TI - Nature of the electronic states in the layered perovskite noncuprate superconductor Sr2RuO4. PMID- 9983351 TI - O(N) tight-binding methods with finite electronic temperature. PMID- 9983352 TI - Specific heat of the half-filled Hubbard chain: A Feynman path-integral Monte Carlo investigation. PMID- 9983353 TI - Nonperturbative results for attractive Hubbard pairings in triangular lattices. PMID- 9983355 TI - Phase coherence in a random one-dimensional system of interacting fermions: A density-matrix renormalization-group study. PMID- 9983354 TI - Pressure-induced charge transfer in Li and Al alloys. PMID- 9983356 TI - Effect of X radiation on the plastic deformation of II-VI compounds. PMID- 9983357 TI - n-type doping in Cd2SnO4: A study by EELS and photoemission. PMID- 9983358 TI - Determination of the electron effective-mass tensor in 4H SiC. PMID- 9983359 TI - Possibility of coherent light emission from excitons in crystalline GaTe. PMID- 9983360 TI - Semiconductor effective charges from tight-binding theory. PMID- 9983361 TI - Ab initio studies of adatom vacancies on the Si(111)-(7 x 7) surface. PMID- 9983362 TI - Surface-sensitive x-ray standing-wave study of Si(111) sqrt(3) x sqrt(3) -Ag. PMID- 9983363 TI - Direct determination of the step-edge formation energies of the energetically stable and unstable double-layer step edges of Si(001). PMID- 9983364 TI - Oxide-cluster nucleation, growth, and saturation on Si(001)-(2 x 1) surfaces: Atomic-scale measurements and models. PMID- 9983365 TI - Doublet structure in the absorption coefficient for tunneling-split intersubband transitions in double quantum wells. PMID- 9983366 TI - Measurement of the optical band gap and crystal-field splitting in wurtzite CdTe. PMID- 9983367 TI - Exchange- and correlation-induced charge transfer observed in independently contacted triple-quantum-well structures. PMID- 9983368 TI - Leggett's conjecture for a mesoscopic ring. PMID- 9983370 TI - Elastic scattering theory for electronic waves in quantum corrals. PMID- 9983371 TI - Size effect on exciton-phonon scattering in quantum wires. PMID- 9983369 TI - Fermi resonance solitary wave on the interface between two layers of organic semiconductors. PMID- 9983372 TI - Transmission of interacting electrons through a one-dimensional periodic potential. PMID- 9983373 TI - Universal excess noise in resonant tunneling via strongly localized states. PMID- 9983374 TI - Photoinhibition of the quantum confined Stark effect in piezoelectric multiple quantum wells. PMID- 9983375 TI - Evidence for resonant electron capture and charge buildup in GaAs/AlxGa1-xAs quantum wells. PMID- 9983377 TI - Cantilever dynamics in quasinoncontact force microscopy: Spectroscopic aspects. PMID- 9983376 TI - Relaxation process of the self-trapping exciton in C60. PMID- 9983378 TI - Local thermodynamic properties of a stepped metal surface: Cu(711). PMID- 9983379 TI - Collective excitations in a single-layer carbon nanotube. PMID- 9983380 TI - Size effects in the ultrafast electronic dynamics of metallic tin nanoparticles. PMID- 9983381 TI - Electronic localization in the cuprates. PMID- 9983382 TI - Periodic boundary conditions in ab initio calculations. II. Brillouin-zone sampling for aperiodic systems. PMID- 9983383 TI - Magnetoresistance extremum at the first-order Verwey transition in magnetite (Fe3O4). PMID- 9983384 TI - Orbital disproportionation of conduction-electron density in cubic lattices with threefold degenerate site orbitals. PMID- 9983385 TI - Electronic transport in the metallic state of oriented poly(p-phenylenevinylene). PMID- 9983386 TI - Shubnikov-de Haas effect and magnetic breakdown in the low-temperature charge density-wave state for the thallium purple bronze TlMo6O17. PMID- 9983387 TI - Analytical results on quantum interference and magnetoconductance for strongly localized electrons in a magnetic field: Exact summation of forward-scattering paths. PMID- 9983388 TI - Electronic polarizability in a correlated electron system with strong covalency. PMID- 9983389 TI - Evidence for PMID- 9983390 TI - Wave propagation in nonlinear photonic band-gap materials. PMID- 9983391 TI - Dislocations and the motion of weakly pinned charge-density waves: Experiments on niobium triselenide containing mobile indium impurities. PMID- 9983392 TI - Substitutional site of Co2+ ions in single-crystalline AgGaS2:Co2+ PMID- 9983393 TI - Spatial distribution of the wave function of the self-trapped exciton in AgCl. PMID- 9983394 TI - Neutron transmutation doping as an experimental probe for AsSe in ZnSe. PMID- 9983395 TI - Electronic and formation energies for deep defects in narrow-gap semiconductors. PMID- 9983397 TI - Density-functional theory of the nonlinear optical susceptibility: Application to cubic semiconductors. PMID- 9983396 TI - Electronic structure and physical properties of NbSi2. PMID- 9983398 TI - Experimental study of the energy-band structure of porous silicon. PMID- 9983399 TI - Photoinduced absorption of oriented poly PMID- 9983400 TI - Observation of resonant Raman scattering at the Si L2,3 core exciton. PMID- 9983401 TI - Pressure-tuned resonance Raman scattering in AgGaSe2. PMID- 9983402 TI - Surface phonons on InP(110) with the adiabatic bond-charge model. PMID- 9983403 TI - Two-stage phase transition of 12 x 1 reconstruction on Si(331). PMID- 9983404 TI - Effect of interfacial bonding on the structural and vibrational properties of InAs/GaSb superlattices. PMID- 9983405 TI - Shallow strained InxGa1-xAs/InyGa1-yAs superlattices embedded in p-i-n diodes: Structural properties and optical response. PMID- 9983406 TI - Direct optical transitions in indirect-gap (Al0.5Ga0.5)0.51In0.49P by atomic ordering. PMID- 9983407 TI - Effect of intersite electron-electron interaction on the concentration of D- ions in quantum wells. PMID- 9983409 TI - Observation of lateral superlattice effects on stepped Cu(001). PMID- 9983408 TI - Electron-spectroscopic study of vertical In1-xGaxAs quantum dots. PMID- 9983410 TI - Microscopic excitation spectroscopy for zero-dimensional quantized states of individual InxGa1-xAs/AlyGa1-yAs quantum dots. PMID- 9983411 TI - Gain without inversion in interband transitions of semiconductor quantum wells from a single-particle perspective. PMID- 9983413 TI - Composite-fermion edge states and transport through nanostructures in the fractional quantum Hall regime. PMID- 9983412 TI - Pseudoultrarelativistic behavior and specification of spinlike effects in the two dimensional electron gas in Kane semiconductors with direct and inverted band structure. PMID- 9983414 TI - Spin-flip scattering in the quantum Hall regime. PMID- 9983415 TI - Microscopic model for a quantum cascade laser. PMID- 9983416 TI - Electron-phonon coupling in a delta -doped n-i-p structure in GaAs. PMID- 9983417 TI - Splitting of electronic levels with positive and negative angular momenta in In0.53Ga0.47As/InP quantum dots by a magnetic field. PMID- 9983418 TI - Site-selective fluorescence studies of poly(p-phenylene vinylene) and its derivatives. PMID- 9983419 TI - Nonlinear optical response due to resonant enhancement of the internal field with particular spatial distribution. PMID- 9983421 TI - Statistics of anyon gas and the factorizable property of thermodynamic quantities. PMID- 9983420 TI - Nonequilibrium dynamics of free quantum-well excitons in time-resolved photoluminescence. PMID- 9983422 TI - Topological phase transition in the nu =2/3 quantum Hall effect. PMID- 9983423 TI - Thermoelectric properties of microstructures with four-probe versus two-probe setups. PMID- 9983424 TI - Two-dimensional modeling of pulsed-laser irradiated a-Si and other materials. PMID- 9983426 TI - Phase transformations of an InSb surface induced by strong femtosecond laser pulses. PMID- 9983425 TI - Linear-chain-model interpretation of resonant Raman scattering in GenSim microstructures. PMID- 9983427 TI - Photoconductance through quantum point contacts: Exact numerical results. PMID- 9983429 TI - Transition to one-dimensional behavior in the optical absorption of quantum-well wires. PMID- 9983428 TI - Compositional dependence of the luminescence of In0.49(AlyGa1-y)0.51P alloys near the direct-indirect band-gap crossover. PMID- 9983430 TI - Binding energy of two-dimensional biexcitons. PMID- 9983431 TI - Theory of semiballistic wave propagation. PMID- 9983432 TI - Microscopic derivation of rate equations for quantum transport. PMID- 9983433 TI - Spatial variations of hot-carrier transmission across CoSi2/Si interfaces on a nanometer scale. PMID- 9983434 TI - Experimental determination of the Fermi surface of thin Sc1-xErxAs epitaxial layers in pulsed magnetic fields. PMID- 9983435 TI - Experimental study of mesoscopic fluctuations in nonlinear conductance and magnetoconductance. PMID- 9983436 TI - Dynamics of nascent current filaments in low-temperature impurity breakdown. PMID- 9983437 TI - Spontaneous coherence and the quantum Hall effect in triple-layer electron systems. PMID- 9983438 TI - Fluctuation kinetics of an isolated Ag(110) step. PMID- 9983439 TI - Formation of (n x 1)-O/Ag(110) overlayers and the role of step-edge atoms. PMID- 9983440 TI - NO2 adsorption on Grafoil between 297 and 12 K. PMID- 9983441 TI - Scanning-tunneling-microscopy study of faceting on high-step-density TaC surfaces. PMID- 9983442 TI - Strain-induced local surface chemical ordering observed by STM. PMID- 9983443 TI - Kinetic analysis of the soldering reaction between eutectic SnPb alloy and Cu accompanied by ripening. PMID- 9983444 TI - Imaging of a surface state from clean Cu(001). PMID- 9983445 TI - Evaporation of single atoms from an adsorbate island or a step to a terrace: Evaporation rate and the underlying atomic-level mechanism. PMID- 9983446 TI - Simple metal clusters in magnetic fields. PMID- 9983448 TI - L-edge x-ray absorption in fcc and bcc Cu metal: Comparison of experimental and first-principles theoretical results. PMID- 9983447 TI - Theoretical study of the binding of Na clusters encapsulated in the C240 fullerene. PMID- 9983449 TI - Static exchange and cluster modeling of core electron shakeup spectra of surface adsorbates: CO/Cu(100). PMID- 9983451 TI - Phase separation in the binary-alloy problem: The one-dimensional spinless Falicov-Kimball model. PMID- 9983450 TI - Conductance step for a single-atom contact in the scanning tunneling microscope: Noble and transition metals. PMID- 9983452 TI - Low-temperature specific heat of the Coulomb glass: Role of correlations. PMID- 9983454 TI - Doped Mott insulator: Results from mean-field theory. PMID- 9983453 TI - Calculation of positron states and annihilation in solids: A density-gradient correction scheme. PMID- 9983455 TI - Dynamics of conversion of conduction electrons into a collective charge-density wave current. PMID- 9983457 TI - Assessment of the polarizabilities ( alpha, beta ) of a nonlinear optical compound PMID- 9983456 TI - Strong effects of photonic band structures on the diffraction of colloidal crystals. PMID- 9983458 TI - Pressure variation of the electrical conductivity of dolomite PMID- 9983459 TI - Defect dipole relaxation in polycrystalline dolomite PMID- 9983460 TI - Spin-polarization effects in (AB2)n polymeric chains. PMID- 9983461 TI - Structure of a-Si:H from Harris-functional molecular dynamics. PMID- 9983462 TI - Stark broadening of impurity absorption lines by inhomogeneous electric fields in highly compensated germanium. PMID- 9983463 TI - Interface stability of Ti(SiGe)2 and SiGe alloys: Tie lines in the ternary equilibrium diagram. PMID- 9983465 TI - Interstitial hydrogen and enhanced dissociation of C-H complexes in GaAs. PMID- 9983464 TI - Two-photon spectroscopy study of ZnS and CdS under hydrostatic pressure. PMID- 9983466 TI - Hydrogen passivation of Se and Te in AlSb. PMID- 9983468 TI - Polarization memory of photoluminescence in amorphous carbon. PMID- 9983467 TI - Recombination and photoluminescence mechanism in hydrogenated amorphous carbon. PMID- 9983469 TI - Elastic constants and related properties of tetrahedrally bonded BN, AlN, GaN, and InN. PMID- 9983470 TI - Theoretical and experimental studies of the interaction between sodium and oligothiophenes. PMID- 9983471 TI - Stress-induced self-organization of nanoscale structures in SiGe/Si multilayer films. PMID- 9983472 TI - Measurement and assignment of the size-dependent optical spectrum in CdSe quantum dots. PMID- 9983473 TI - Size dependence of exciton fine structure in CdSe quantum dots. PMID- 9983474 TI - Intrawell and interwell magnetoexcitons in InxGa1-xAs/GaAs coupled double quantum wells. PMID- 9983476 TI - Influence of ferromagnetic spin waves on persistent currents in one-dimensional mesoscopic rings. PMID- 9983475 TI - Quantum and transport mobilities in delta -doped semiconductors. PMID- 9983477 TI - Conductance through a quantum dot in an Aharonov-Bohm ring. PMID- 9983478 TI - Current fluctuations in mesoscopic systems with Andreev scattering. PMID- 9983480 TI - Resonance states of open quantum dots. PMID- 9983479 TI - Quasi-one-dimensional transport near the ballistic limit. PMID- 9983481 TI - Resonant tunneling in CdTe/Cd1-xMgxTe double-barrier single-quantum-well heterostructures. PMID- 9983482 TI - Edge states of integral quantum Hall states versus edge states of antiferromagnetic quantum spin chains. PMID- 9983483 TI - Optical absorption near the band edge in GaN grown by metalorganic chemical-vapor deposition. PMID- 9983484 TI - Femtosecond coherent fields induced by many-particle correlations in transient four-wave mixing. PMID- 9983485 TI - Magnetic-field-induced formation of exciton magnetic polarons in ZnSe/Zn1-xMnxSe quantum-well structures. PMID- 9983486 TI - Perpendicular-electric-field dependence of exciton binding energy studied by continuous-wave photoluminescence. PMID- 9983487 TI - Magnetoluminescence studies of InyAl1-yAs self-assembled quantum dots in AlxGa1 xAs matrices. PMID- 9983488 TI - Linear and nonlinear optical properties of realistic quantum-wire structures: The dominant role of Coulomb correlation. PMID- 9983489 TI - Slow relaxation of excited states in strain-induced quantum dots. PMID- 9983491 TI - Green's functions theory for semiconductor-quantum-well laser spectra. PMID- 9983490 TI - Direct observation of magnetophonon resonances in Landau-level lifetimes of a semiconductor heterostructure. PMID- 9983492 TI - Comparison of classical and tight-binding molecular dynamics for silicon growth. PMID- 9983493 TI - Boundary conditions and spurious solutions in envelope-function theory. PMID- 9983494 TI - X-ray-absorption spectroscopy of CoSi2. PMID- 9983495 TI - Time-resolved spontaneous emission of excitons in a microcavity: Behavior of the individual exciton-photon mixed states. PMID- 9983496 TI - Exciton dynamics in a single quantum well with self-assembled islands. PMID- 9983497 TI - Dissipative tunneling in asymmetric double-quantum-well systems: A coherence phenomenon. PMID- 9983498 TI - Exciton fine structure in undoped GaN epitaxial films. PMID- 9983500 TI - Fokker-Planck description of the transfer-matrix limiting distribution in the scattering approach to quantum transport. PMID- 9983499 TI - Width dependence of quantum lifetimes in GaAs/AlxGa1-xAs heterostructures. PMID- 9983502 TI - Magnus force on skyrmions in ferromagnets and quantum Hall systems. PMID- 9983501 TI - Exact effective action for fermions in one dimension with backscattering at a boundary. PMID- 9983503 TI - Mobility of grain boundary dislocations during the conservative untwisting of PMID- 9983504 TI - Photoelectron spectroscopy and scanning tunneling microscopy studies of the initial growth of the Sm-on-Pt(100) interface. PMID- 9983505 TI - Role of the tip atom in STM and AFM: Theory of atom transfer. PMID- 9983507 TI - Dynamical model for the interpretation of the geometry of the (4 x 2) CO layer adsorbed on MgO (001). PMID- 9983506 TI - Anisotropic diffusion between the step-up and the step-down directions on a Si(001) surface. PMID- 9983508 TI - Electronic structure of Eu and Yb graphite intercalation compounds. PMID- 9983509 TI - Multifractal analysis of the spatial distribution of secondary-electron emission sites. PMID- 9983511 TI - CO on copper clusters: Orbital symmetry rules. PMID- 9983510 TI - Mossbauer study of the proximity gettering of cobalt atoms to He-induced nanosized voids in c-Si. PMID- 9983512 TI - Discrete-variational X alpha calculations of C60Fx with x=0, 36, and 48. PMID- 9983513 TI - Spectral statistics near the quantum percolation threshold. PMID- 9983514 TI - Radiative recombination and self-trapping of excitons via biexciton states in RbI. PMID- 9983515 TI - Optical-bias effect on transient electron-drift measurements in a-Si:H: Implications on the distribution and capture cross sections of the dangling bonds. PMID- 9983516 TI - Relaxation dynamics of electrons between Landau levels in GaAs. PMID- 9983517 TI - Coherent phonon-plasmon modes in GaAs:AlxGa1-xAs heterostructures. PMID- 9983518 TI - Etching of double-height-stepped Si(100)-2 x 1: Steps and their interactions. PMID- 9983519 TI - Adsorbed and substituted Sb dimers on GaAs(001). PMID- 9983520 TI - Valence-band maximum in the layered semiconductor WSe2: Application of constant energy contour mapping by photoemission. PMID- 9983522 TI - Concentrated oscillator strength of one-dimensional excitons in quantum wires observed with photoluminescence excitation spectroscopy. PMID- 9983521 TI - Magnetoexciton anisotropy in quantum wells versus quantum wires. PMID- 9983523 TI - Evidence of the ordered growth of monomolecular ZnTe islands in CdTe/(Cd,Zn)Te quantum wells on a nominal (001) surface. PMID- 9983524 TI - Edge-state transport in separately contacted double-layer quantum Hall systems. PMID- 9983525 TI - Ultrafast in-well screening of the piezoelectric field in (111) quantum wells. PMID- 9983526 TI - Crystal azimuthal-angle dependence of excited-state production and core rearrangement processes in Ne+ scattering on Al(111). PMID- 9983527 TI - Load-dependent topographic and friction studies of individual ion tracks in layered materials by scanning force microscopy and lateral force microscopy. PMID- 9983529 TI - Binding energy of the stabilized uniform interstitial electron gas in transition metals. PMID- 9983528 TI - Influence of gradient corrections on the bulk and surface properties of TiO2 and SnO2. PMID- 9983531 TI - Approach to density-functional ionization energy. PMID- 9983530 TI - Electronic states of the theta ' phase in Cu-Al alloys as compared to C16-CuAl2: Cu L alpha emission excited directly by undulator radiation. PMID- 9983532 TI - Depinning transition in Mott-Anderson insulators. PMID- 9983533 TI - Influence of intra-atomic correlation effects on 3d states in transition-metal compounds. PMID- 9983534 TI - Environment-dependent tight-binding potential model. PMID- 9983535 TI - Evidence for ideal insulating or conducting state in a one-dimensional integrable system. PMID- 9983536 TI - LO-phonon and plasmon coupling in neutron-transmutation-doped GaAs. PMID- 9983537 TI - Thermodynamic properties of particles with intermediate statistics. PMID- 9983538 TI - Resonant-tunneling spectroscopy of coupled hole subbands in strained Si/SiGe triple-barrier structures. PMID- 9983539 TI - Monte Carlo simulation of In surface segregation during the growth of InxGa1-xAs on GaAs(001). PMID- 9983540 TI - Vicinal Si(100) surfaces under external strain. PMID- 9983541 TI - Persistent current of one-dimensional perfect rings under the canonical ensemble. PMID- 9983542 TI - Near-infrared photonic band gap of two-dimensional triangular air-rod lattices as revealed by transmittance measurement. PMID- 9983543 TI - Crossover behavior of the conductance oscillations in a quasi-one-dimensional ring in the ballistic limit. PMID- 9983544 TI - Absorption spectra of GaAs/AlxGa1-xAs random superlattices at 2 K. PMID- 9983545 TI - Quantization effects in the conductance of metallic contacts at room temperature. PMID- 9983546 TI - Plasmons in a spatially modulated quasi-one-dimensional quantum wire. PMID- 9983547 TI - Interface ordering in Sim/Gen monolayer superlattices: A photoluminescence study. PMID- 9983548 TI - Tunneling spectroscopy of quantum charge fluctuations in the Coulomb blockade. PMID- 9983549 TI - Electron effective mass and nonparabolicity in Ga0.47In0.53As/InP quantum wells. PMID- 9983550 TI - Observation of conductance quantization of ballistic metallic point contacts at room temperature. PMID- 9983551 TI - Skyrmion excitations in quantum Hall systems. PMID- 9983552 TI - Time-dependent resonant tunneling via two discrete states. PMID- 9983554 TI - Ground-state wave function of the fractional quantum Hall effect. PMID- 9983553 TI - Local far-infrared spectroscopy of edge states in the quantum Hall regime. PMID- 9983556 TI - Pendulating orbits in large metal clusters. PMID- 9983555 TI - Composite-fermion wave functions in higher Landau levels. PMID- 9983557 TI - Impurity-induced modulations in PdxNbSe3 coupled to charge-density-wave formation. PMID- 9983558 TI - Effects of electrode interactions observed in a mechanically controllable break junction. PMID- 9983559 TI - Modifications of the electronic and magnetic properties of ultrathin Ni/Cu(100) films induced by stepwise oxidation. PMID- 9983560 TI - Structural study of the Si(100)2 x 2-In surface. PMID- 9983561 TI - Spin-reorientation transition in ultrathin Tb/Co films. PMID- 9983562 TI - Quantum vortex melting in Nb/CuMn multilayers. PMID- 9983563 TI - Experimental determination of the energy barrier for the Li262+ cluster. PMID- 9983564 TI - Ordering of a prototypical conjugated molecular system during monolayer growth on the (1 x 2)-Au(110) surface. PMID- 9983565 TI - Electronic excitation of O2 molecules physisorbed on Ag(110). PMID- 9983567 TI - Self-energy of electrons in graphite intercalation compounds. PMID- 9983566 TI - Electronic structure of Ce-filled skutterudites. PMID- 9983568 TI - Local electronic structure of ZnS and ZnSe doped by Mn, Fe, Co, and Ni from x-ray absorption near-edge structure studies. PMID- 9983569 TI - Ground-state properties and relative stability between the L12 and DOa phases of Ni3Al by Nb substitution. PMID- 9983570 TI - Ab initio model-potential embedded-cluster study of Jahn-Teller parameters and electronic transition energies of Cr2+ in oxide and fluoride octahedral coordination. PMID- 9983571 TI - Electronic structure and half-metallic transport in the La1-xCaxMnO3 system. PMID- 9983573 TI - Perturbation formalism of an exact representation for the t-J model. PMID- 9983572 TI - Electronic structure of early 3d-transition-metal oxides by analysis of the 2p core-level photoemission spectra. PMID- 9983574 TI - Generalized-gradient approximations to density-functional theory: A comparative study for atoms and solids. PMID- 9983575 TI - Distribution of local density of states in disordered metallic samples: Logarithmically normal asymptotics. PMID- 9983576 TI - Comparison of the electronic structures and energetics of ferroelectric LiNbO3 and LiTaO3. PMID- 9983578 TI - Correlation energy and its temperature dependence. PMID- 9983577 TI - Influence of weak dissipation on the photonic band structure of periodic composites. PMID- 9983580 TI - Slave-boson study in the SU(2)-invariant representation: Coupled layers in the one-band Hubbard model. PMID- 9983579 TI - Energy spectrum of two-dimensional tight-binding electrons in a spatially varying magnetic field. PMID- 9983581 TI - Phase diagram for charge-density waves in a magnetic field. PMID- 9983583 TI - Pair breaking in semiclassical singlet small-bipolaron hopping. PMID- 9983582 TI - Electron-positron momentum density in diamond, Si, and Ge. PMID- 9983585 TI - Nonlinear Zeeman behavior of Cu2+ centers in ZnS and CdS explained by a Jahn Teller effect. PMID- 9983584 TI - Nonlinear excitations in polyacene. PMID- 9983586 TI - Plasmon Raman scattering and photoluminescence of heavily doped n-type InP near the Gamma -X crossover. PMID- 9983588 TI - Phonons as a probe of short-range order in Si1-xCx alloys. PMID- 9983587 TI - Quantum theory for exciton polaritons in a real-space representation. PMID- 9983589 TI - Free energy of the concerted-exchange mechanism for self-diffusion in silicon. PMID- 9983590 TI - Germanium negative-U center in GaAs. PMID- 9983591 TI - Carrier localization of as-grown n-type gallium nitride under large hydrostatic pressure. PMID- 9983592 TI - Solitary-wave conduction in p-type Ge under time-dependent voltage bias. PMID- 9983594 TI - Method of linear combination of structural motifs for surface and step energy calculations: Application to GaAs(001). PMID- 9983593 TI - Enhancement of electron-hole exchange interaction in CdSe nanocrystals: A quantum confinement effect. PMID- 9983595 TI - Thermally activated intersubband and hopping transport in center-doped p-type GaAs/AlxGa1-xAs quantum wells. PMID- 9983596 TI - Low coverages of lithium on Si(001) studied with STM and ARUPS. PMID- 9983598 TI - Band structures of II-VI semiconductors using Gaussian basis functions with separable ab initio pseudopotentials: Application to prediction of band offsets. PMID- 9983597 TI - Epitaxy of CoSix (1c(2 x 2) order-disorder phase transition. PMID- 9983964 TI - Energetics of vicinal surfaces of fcc (111) transition metals. PMID- 9983965 TI - Structure of the p(2 x 3) Ni(110)-N surface studied by scanning tunneling microscopy. PMID- 9983966 TI - Island-size distributions in submonolayer epitaxial growth: Influence of the mobility of small clusters. PMID- 9983967 TI - Al on Si(111): Phase diagram and atomic mechanisms. PMID- 9983969 TI - Molecular-dynamics study of compressive stress generation. PMID- 9983968 TI - Field desorption of lithium. PMID- 9983971 TI - Surface Brillouin-scattering spectroscopy of media with nonuniform acousto-optic properties. PMID- 9983970 TI - Energies and lifetimes of atomic Rydberg states near metal surfaces. PMID- 9983972 TI - Oxidation of epitaxial Ce films. PMID- 9983973 TI - Kinetics of nucleation in surfactant-mediated epitaxy. PMID- 9983974 TI - Molecular-dynamics simulations of slow copper cluster deposition. PMID- 9983976 TI - Optical absorption of 4d fcc transition-metal particles: Study of the contribution of the conduction-electron density to the correlation interaction. PMID- 9983975 TI - Surface-enhanced second-harmonic diffraction: Experimental investigation of selective enhancement. PMID- 9983977 TI - Magnetic interactions in TDAE-C60. PMID- 9983979 TI - Polarization-dependent optical parameters of arbitrarily anisotropic homogeneous layered systems. PMID- 9983978 TI - Erratum: Double chain structures on the Sb-terminated GaAs(111)B surface PMID- 9983980 TI - Electronic structure of cerium in the self-interaction-corrected local-spin density approximation. PMID- 9983981 TI - Electronic structure of nanometric Si/C, Si/N, and Si/C/N powders studied by both x-ray-photoelectron and soft-x-ray spectroscopies. PMID- 9983982 TI - Renormalization approach for transport and electronic properties of conducting polymers. PMID- 9983983 TI - Prospects for non-Fermi-liquid behavior of a two-level impurity in a metal. PMID- 9983984 TI - Localized low-energy excitations in strongly correlated metals. PMID- 9983985 TI - Electronic structure of rare-earth pnictides. PMID- 9983986 TI - Theoretical study of the evolution of electronic band structure of polythiophene due to bipolaron doping. PMID- 9983987 TI - Electron valence band of zirconium tetrafluoride. PMID- 9983988 TI - Importance of matrix correlations in dye-doped solid rare gases: A hole-burning study. PMID- 9983989 TI - Third-harmonic-generation spectroscopy of poly(p-phenylenevinylene): A comparison with oligomers and scaling laws for conjugated polymers. PMID- 9983990 TI - Electronic structure of defects and impurities in III-V nitrides: Vacancies in cubic boron nitride. PMID- 9983991 TI - Equation of state of metallic fluids near the critical point of phase transition. PMID- 9983992 TI - Transport properties, thermodynamic properties, and electronic structure of SrRuO3. PMID- 9983993 TI - Composition dependence of the structure and electronic properties of liquid Ga-Se alloys studied by ab initio molecular dynamics simulation. PMID- 9983995 TI - Hydrogen solubility and network stability in amorphous silicon. PMID- 9983994 TI - Tight-binding molecular-dynamics study of density-optimized amorphous GaAs. PMID- 9983996 TI - Optically enhanced high-field NMR of GaAs. PMID- 9983998 TI - Density-functional-based construction of transferable nonorthogonal tight-binding potentials for B, N, BN, BH, and NH. PMID- 9983997 TI - Hydrostatic pressure dependence of isoelectronic bound excitons in beryllium doped silicon. PMID- 9983999 TI - Visible and near-infrared ultrafast optical dynamics of hexamethylsexithiophene in solution. PMID- 9984001 TI - Mechanism of carrier photogeneration in amorphous selenium: Fast transient photoconductivity. PMID- 9984000 TI - First-principles calculations of p-type impurities in cubic SiC. PMID- 9984002 TI - High-pressure effects on high-field magnetophotoluminescence in Cd1-xMxSe (M=Mn,Co). PMID- 9984003 TI - Role of chi (3) anisotropy in the generation of squeezed light in semiconductors. PMID- 9984004 TI - Ab initio study of the volume dependence of dynamical and thermodynamical properties of silicon. PMID- 9984006 TI - Aging effects on the transport properties in conducting polymer polypyrrole. PMID- 9984005 TI - Photoconductivity of poly(2,5-diheptyloxy-p-phenylene vinylene) in the air atmosphere: Magnetic-field effect and mechanism of generation and recombination of charge carriers. PMID- 9984007 TI - Changes of the occupied density of defect states of a-Si:H upon illumination. PMID- 9984009 TI - Electronic structure and EPC stability of the alpha -Sn/InSb(111)A nonpolar-polar heterojunction interface. PMID- 9984008 TI - Resonant photoemission studies of Pb1-xEuxTe. PMID- 9984010 TI - Recombination and thermal emission of excitons in shallow CdTe/Cd1-xMgxTe quantum wells. PMID- 9984012 TI - Flipping silicon dimers on Si(100) using scanning tip microscopy: A theoretical investigation. PMID- 9984011 TI - Resonant interaction of phonons with surface vibrational modes in a finite-size superlattice. PMID- 9984013 TI - Electron states and luminescence transition in porous silicon. PMID- 9984015 TI - Surface segregation and ordering in III-V semiconductor alloys. PMID- 9984014 TI - Surface-defect formation on heavily doped InAs and GaAs layers studied by scanning tunneling microscopy. PMID- 9984016 TI - Thermal formation of Zn-dopant-vacancy defect complexes on InP(110) surfaces. PMID- 9984017 TI - Stability, dynamical properties, and melting of a classical bilayer Wigner crystal. PMID- 9984018 TI - Sulfide-passivated GaAs(001). I. Chemistry analysis by photoemission and reflectance anisotropy spectroscopies. PMID- 9984019 TI - Sulfide-passivated GaAs (001). II. Electronic properties. PMID- 9984021 TI - Generalization of the k PMID- 9984020 TI - Capacitance-voltage characteristics of a Schottky junction containing SiGe/Si quantum wells. PMID- 9984022 TI - Model for carrier dynamics and photoluminescence quenching in wet and dry porous silicon thin films. PMID- 9984023 TI - Localization and delocalization of an electron in biased and unbiased quantum wells driven by a mono- and bichromatic laser field. PMID- 9984024 TI - Electron correlations in antidot arrays in a magnetic field. PMID- 9984026 TI - Multiple-quantum resonant reflection of ballistic electrons from a high-frequency potential step. PMID- 9984025 TI - Size dependence of the changeover from geometric to magnetic confinement in In0.53Ga0.47As/InP quantum wires. PMID- 9984027 TI - Two-dimensional electron gas in a linearly varying magnetic field: Quantization of the electron and current density. PMID- 9984028 TI - Fermi-edge singularity of the Tomonaga-Luttinger liquids with spin-split Fermi points. PMID- 9984029 TI - Interface broadening and Raman scattering in Si1-xGex/Si superlattices. PMID- 9984030 TI - Excitation-intensity-dependent photoluminescence in semiconductor quantum wells due to internal electric fields. PMID- 9984032 TI - Time-resolved luminescence studies in an n-type Zn1-xCdxSe/ZnSySe1-y quantum well. PMID- 9984031 TI - Optical spectroscopy in (Zn,Cd)Se-ZnSe graded-index separate-confinement heterostructures. PMID- 9984033 TI - Angle-resolved photoemission from a GaAs (1-bar 1-bar 1-bar)-2 x 2 surface: Off normal emission study. PMID- 9984034 TI - Core level and valence-band studies of the (111)2 x 2 surfaces of InSb and InAs. PMID- 9984035 TI - Temperature dependence of strains and stresses in undercritical cubic superlattices and heterojunctions. PMID- 9984036 TI - Phonon properties of one-dimensional nanocrystalline solids. PMID- 9984037 TI - Solid-phase epitaxy induced by low-power pulsed-laser annealing of III-V compound semiconductors. PMID- 9984038 TI - Mechanism of electron-beam doping in semiconductors. PMID- 9984039 TI - Three-dimensional x-y model with a Chern-Simons term. PMID- 9984040 TI - Metallic character of the K/Si(100)-(2 x 1) interface at saturation coverage: A Mott-Hubbard model calculation of its near-Fermi-level band structure. PMID- 9984041 TI - Magnetotransport studies of strongly disordered annealed amorphous Fe/Si multilayers. PMID- 9984042 TI - Photoluminescence spectra of GaP/AlP short-period superlattices under high magnetic fields. PMID- 9984043 TI - Bipolaron lattice formation at metal-polymer interfaces. PMID- 9984044 TI - Time-periodic behavior of multiband superlattices in static electric fields. PMID- 9984045 TI - Quantum transport in the presence of a finite-range time-modulated potential. PMID- 9984046 TI - Hot-electron transport through Au/GaAs and Au/GaAs/AlAs heterojunction interfaces: Ballistic-electron-emission-microscopy measurement and Monte Carlo simulation. PMID- 9984047 TI - Renormalization group and exact diagonalization studies of Hubbard rings with impurities. PMID- 9984048 TI - Magnetoresistance of two-dimensional mesoscopic structures: A variational approach. PMID- 9984049 TI - Landau-Zener transitions and dissipation in a mesoscopic ring. PMID- 9984050 TI - Observation of oscillatory linewidth behavior in the magnetoluminescence of a modulation-doped InxGa1-xAs quantum well. PMID- 9984052 TI - III-V diluted magnetic semiconductor: Substitutional doping of Mn in InAs. PMID- 9984051 TI - Magneto-optic study of the interface in semimagnetic semiconductor heterostructures: Intrinsic effect and interface profile in CdTe-Cd1-xMnxTe. PMID- 9984053 TI - Shape of molecular adsorbates in STM images: A theoretical study of benzene on Pt(111). PMID- 9984054 TI - Potential-energy surface for H2 dissociation over Pd(100). PMID- 9984055 TI - Ab initio study of AlN and alpha -SiC (112-bar0) surface relaxation. PMID- 9984056 TI - Phase diagrams and rotated incommensurate phases of K, Rb, and Cs adsorbed on Ag(111). PMID- 9984057 TI - Theory of segregation using the equivalent-medium approximation and bond-strength modifications at surfaces: Application to fcc Pd-X alloys. PMID- 9984058 TI - Ab initio calculations of energies and self-diffusion on flat and stepped surfaces of Al and their implications on crystal growth. PMID- 9984060 TI - Background removal in surface electron spectroscopy: Influence of surface excitations. PMID- 9984059 TI - Hydrogen absorption by thin Pd/Nb films deposited on glass. PMID- 9984061 TI - Structure and bonding of small stoichiometric lithium oxide clusters. PMID- 9984062 TI - Exactly solvable model of surface second-harmonic generation. PMID- 9984063 TI - Surface-induced bond anharmonicity probed through a two-phonon bound state: Methoxide adsorbed on Mo(110). PMID- 9984064 TI - Double surface-bulk melting and suppression of overheating at first-order phase transitions. PMID- 9984065 TI - Photoemission studies of the electronic properties of the Ce/Fe(100) and Ce/Fe(110) interfaces: Formation of a strongly hybridized cerium phase. PMID- 9984066 TI - Comment on "Constraints on pairings in the Hubbard model" PMID- 9984068 TI - Strongly interacting model for antiferromagnetism in one-dimensional C60 polymers: AC60. PMID- 9984067 TI - Observation of Zeeman splitting in universal conductance fluctuations. PMID- 9984070 TI - Excitonic exchange splitting and Stokes shift in Si nanocrystals and Si clusters. PMID- 9984069 TI - Self-energy correction to unrestricted Hartree-Fock solutions of lattice models for 3d transition-metal oxides. PMID- 9984071 TI - Ab initio prediction of GaN (101-bar0) and (110) anomalous surface relaxation. PMID- 9984072 TI - Self-aggregation of quantum dots for very thin InAs layers grown on GaAs. PMID- 9984073 TI - Observation of ballistic transport in the upper subband of a two-dimensional electron system. PMID- 9984074 TI - Magnetic-field dependence of the level spacing of a small electron droplet. PMID- 9984076 TI - Optical anisotropy in 5-nm-scale T-shaped quantum wires fabricated by the cleaved edge overgrowth method. PMID- 9984075 TI - Dynamics of electron capture into quantum wires. PMID- 9984077 TI - Excitonic lifetimes in (Zn,Cd)Se/ZnSe and ZnSe/Zn(Se,S) quantum wires. PMID- 9984078 TI - Lateral correlation in mesoscopic structures on the silicon (001) surface determined by grating x-ray diffuse scattering. PMID- 9984079 TI - Grain-boundary dissociation by the emission of stacking faults. PMID- 9984080 TI - Selective laser removal of the dimer layer from Si(100) surfaces revealed by scanning tunneling microscopy. PMID- 9984081 TI - Helium-adsorbate cross section on highly corrugated substrates. PMID- 9984082 TI - H-enhanced mobility and defect formation at surfaces: H on Be(0001). PMID- 9984083 TI - Resonantlike desorption of negative ions by core-level excitation under electron bombardment. PMID- 9984085 TI - Measurement of the hard-sphere equation of state using screened charged polystyrene colloids. PMID- 9984084 TI - Trapped charge migration in BaFBr:Eu2+: The recuperation of photostimulated luminescence. PMID- 9984086 TI - Effect of quantum fluctuations on structural phase transitions in SrTiO3 and BaTiO3. PMID- 9984087 TI - SC4: A metallic phase of carbon at terapascal pressures. PMID- 9984088 TI - Thermal residual stress in composites with anisotropic interphases. PMID- 9984090 TI - Microscopic modeling of the growth of order in an alloy: Nucleated and continuous ordering. PMID- 9984089 TI - Thermodynamics of polymorphism in the AC60 (A=K, Rb, Cs) alkali fullerides. PMID- 9984091 TI - Scaling behavior of the localization length in random dimer harmonic chains with thermal correlations. PMID- 9984092 TI - Spectral properties of the Vicsek fractal. PMID- 9984093 TI - Frequency dependence of phonon-polariton damping in lithium niobate. PMID- 9984094 TI - Critical exponents of self-avoiding walks in three dimensions. PMID- 9984095 TI - Negative spin-valve effect in Co65Fe35/Ag/(Co65Fe35)50Gd50 trilayers. PMID- 9984097 TI - Mean-field theory of the spin-Peierls state under magnetic field: Application to CuGeO3. PMID- 9984096 TI - Ground-state dynamical correlation functions: An approach using the density matrix renormalization-group method. PMID- 9984098 TI - Large magnetothermopower in La0.67Ca0.33MnO3 films. PMID- 9984100 TI - Possible quadrupolar ordering in a Kondo-lattice compound Ce3Pd20Ge6. PMID- 9984099 TI - Integrable open-boundary conditions for the one-dimensional Bariev chain. PMID- 9984101 TI - Dynamical universality class of Brownian motion and exact results for a single impurity s=1/2 XY chain. PMID- 9984103 TI - Temperature-dependent biquadratic coupling in antiferromagnetically coupled Fe/FeSi multilayers. PMID- 9984102 TI - Magnetic properties of beta -FeSi2 single crystals. PMID- 9984105 TI - Structural and magnetic properties of trigonal iron. PMID- 9984104 TI - Accurate determination of the exchange constant in Sr2CuO3 from recent theoretical results. PMID- 9984106 TI - Onsager reaction field theory of the one-dimensional ferromagnet with long-range interactions. PMID- 9984108 TI - Estimation of superconducting transition temperature in metallic carbon nanotubes. PMID- 9984107 TI - Interlayer magnetic coupling: Effect of interface roughness. PMID- 9984109 TI - Conserving approximation for the three-band Hubbard model: Flat quasiparticle dispersion. PMID- 9984110 TI - Antiferromagnetic interactions and the superconducting gap function. PMID- 9984111 TI - Frequency dependence of giant Shapiro steps in ordered and site-disordered proximity-coupled Josephson-junction arrays. PMID- 9984112 TI - Determination of the gap structure in UPt3 by thermal conductivity. PMID- 9984114 TI - Rigorous results on superconducting ground states for attractive extended Hubbard models. PMID- 9984113 TI - Neutron scattering from a collective spin fluctuation mode in a CuO2 bilayer. PMID- 9984116 TI - Surface barrier and lower critical field of the powdered Pr1.85Ce0.15CuO3.98 superconductor. PMID- 9984115 TI - Single-crystal neutron-diffraction structures of reduced and oxygenated Nd2 xCexCuOy. PMID- 9984117 TI - Anisotropic pairing caused by unscreened long-range interactions. PMID- 9984118 TI - Inhomogeneous spin structures in high-Tc cuprates. PMID- 9984119 TI - Thermoelectric power of high-pressure synthesized CuBa2Ca3Cu4O11- delta. PMID- 9984120 TI - Second-order elastic constants of AgCl from 20 to 430 degreesC. PMID- 9984121 TI - Temperature-dependent concentration quenching and site-dependent effects of Nd3+ fluorescence in fluorophosphate glasses. PMID- 9984122 TI - ENDOR study of an O- ion observed in x-ray-irradiated carbonated hydroxyapatite powders. PMID- 9984123 TI - Possible disordered ground states for layered solids and their diffraction patterns. PMID- 9984124 TI - Effects of pressure and ambient species on orientational ordering in solid C70. PMID- 9984125 TI - Ferroelectric displacement of atoms in Rochelle salt. PMID- 9984127 TI - Electrostatic properties in zeolite-type materials from high-resolution x-ray diffraction: The case of natrolite. PMID- 9984126 TI - Optical second-harmonic generation at interfaces of ferroelectric nanoregions in SrSiO3:Ca. PMID- 9984128 TI - Raman scattering and the evolution of polar order in Li-doped and Nb-doped KTaO3. PMID- 9984129 TI - Interaction energies of 111In perturbed-angular-correlation probes with 3d and 4sp impurities in Ag, Pd, and Rh. PMID- 9984130 TI - Universal features of the equation of state of solids from a pseudospinodal hypothesis. PMID- 9984131 TI - Microscopic dynamics of glycerol in its crystalline and glassy states. PMID- 9984133 TI - From a discrete to a continuum model for static antiphase boundaries. PMID- 9984132 TI - EXAFS studies of rare-earth metaphosphate glasses. PMID- 9984135 TI - Weighted two-particle Green's functions in the coherent-potential approximation. PMID- 9984134 TI - Elastic and anelastic properties, vibrational anharmonicity, and fractal bond connectivity of superionic glasses. PMID- 9984136 TI - Approximation of excitonic absorption in disordered systems using a compositional component-weighted coherent-potential approximation. PMID- 9984138 TI - Electron radiation damage and Li-colloid creation in Li2O. PMID- 9984137 TI - Asymmetry in the Brillouin spectra of organic fluids exposed to a temperature gradient. PMID- 9984139 TI - Dynamics of solvation in supercooled liquids confined to the pores of sol-gel glasses. PMID- 9984140 TI - Mid-IR and far-IR investigation of AgI-doped silver diborate glasses. PMID- 9984141 TI - Low-frequency noise in a phonon system of disordered insulators. PMID- 9984142 TI - Reconstruction of spectral densities of anharmonic phonons from their moments via the effective-potential method and the continued-fraction approach. PMID- 9984143 TI - Transverse interplanar forces and phonon spectra of strained Si, Ge, and Si/Ge superlattices. PMID- 9984144 TI - Secondary excitons in alkali halide crystals. PMID- 9984145 TI - Anharmonic interactions in beryllium oxide. PMID- 9984146 TI - Perturbed-angular-correlation study of 111Cd and 181Ta nuclear-quadrupole relaxations in the rare-earth dihydride DyH2+/- delta. PMID- 9984147 TI - Memory-function approach to interacting quasiparticle-boson systems. PMID- 9984148 TI - Intrinsic localized modes in the bulk and at the surface of anharmonic diatomic chains. PMID- 9984149 TI - Pressure dependence of Born effective charges, dielectric constant, and lattice dynamics in SiC. PMID- 9984150 TI - Elastic behavior of materials with multifractal structures. PMID- 9984151 TI - Relationship between morphology and magnetic behavior for Gd thin films on W(110). PMID- 9984152 TI - Electronic transport in ultrathin magnetic multilayers. PMID- 9984153 TI - Quantum magnetic oscillations and rapid oscillation phenomena in (TMTSF)2X (X=ClO4 and NO3). PMID- 9984154 TI - Magnetism in CePtPb. PMID- 9984155 TI - Magnetization steps in Pb1-xEuxSe: Determination and identification of the dominant antiferromagnetic exchange constant. PMID- 9984156 TI - Reflection of electromagnetic radiation from structured metallic magnets. PMID- 9984157 TI - Conversion-electron Mossbauer study of the interfacial roughness in MBE-grown Ni80Fe20/Fe50Mn50 (111) bilayers. PMID- 9984158 TI - Model of thermally activated magnetization reversal in thin films of amorphous rare-earth-transition-metal alloys. PMID- 9984160 TI - Structure and magnetism of Fe/Si multilayers grown by ion-beam sputtering. PMID- 9984159 TI - Magnetism in the Hubbard model: An effective spin Hamiltonian approach. PMID- 9984161 TI - Dynamical properties of two coupled Hubbard chains at half-filling. PMID- 9984162 TI - Magnetic and structural properties of thin Fe films grown on Ni/Si. PMID- 9984163 TI - Magnetism in complex atomic structures: Grain boundaries in nickel. PMID- 9984164 TI - NMR study of the heavy-fermion alloy Ce(Cu1-xNix)2Ge2. PMID- 9984166 TI - Magnetic correlations of fine ferromagnetic particles studied by small-angle neutron scattering. PMID- 9984165 TI - Magnetic anisotropy of glide-distorted fcc and of bcc ultrathin Fe/Cu(001) films. PMID- 9984168 TI - Intermediate-coupling theory of the spin polaron in the t-J model. PMID- 9984167 TI - Inelastic-neutron-scattering investigation of the spin-Peierls system CuGeO3. PMID- 9984169 TI - Semiclassical description of angle-dependent magnetoresistance oscillations in quasi-one-dimensional metals. PMID- 9984170 TI - 87Rb NMR and the T' problem in Rb3C60. PMID- 9984171 TI - Magnetic impurity coupled to interacting conduction electrons. PMID- 9984172 TI - 3s photoemission spectra of Fe/Cu(100) films. PMID- 9984174 TI - Superheating fields of superconductors: Asymptotic analysis and numerical results. PMID- 9984173 TI - Tunneling spectroscopy of the superconducting energy gap in RNi2B2C (R=Y and Lu). PMID- 9984176 TI - Hydrodynamics of spatially ordered superfluids. PMID- 9984175 TI - Final-state effects on superfluid 4He in the deep inelastic regime. PMID- 9984177 TI - Superconducting proximity effect through high-quality high-conductance tunnel barriers. PMID- 9984179 TI - Fermi-liquid damping and NMR relaxation in superconductors. PMID- 9984178 TI - Anisotropic magnetoresistance of single-crystal HoNi2B2C and the interplay of magnetic and superconducting order. PMID- 9984180 TI - Heat transport and the nature of the order parameter in superconducting UPt3. PMID- 9984182 TI - Diamagnetic response of normal-metal-superconductor double layers. PMID- 9984181 TI - Magnetic hysteresis from the geometrical barrier in type-II superconducting strips. PMID- 9984184 TI - One-dimensional t-J model from a variational viewpoint. PMID- 9984183 TI - Phase diagram of superconductors from nonperturbative flow equations. PMID- 9984185 TI - Anisotropic superconductivity: (s+d)-wave model, (d+s)-wave model and the effect of normal impurities. PMID- 9984186 TI - Vortex state in a d-wave superconductor. PMID- 9984187 TI - Comparison of superconducting flux pinning due to ion irradiation and fishtail effects. PMID- 9984188 TI - Vortex-state resistance near parallel orientation in layered superconductors. PMID- 9984190 TI - Anisotropy studies on aligned HgBa2CaCu2O6+ delta powder: Confirmation of the collective-pinning theory for anisotropic materials. PMID- 9984189 TI - Monte Carlo simulation of hard-core bosons on a three-dimensional lattice. PMID- 9984191 TI - Orthorhombically mixed s- and dx2-y2-wave superconductivity and Josephson tunneling. PMID- 9984192 TI - Ion-size effect on normal-state transport properties in R0.8Pr0.2Ba2Cu3O7-y systems (R=Yb, Er, Dy, Gd, Eu, and Nd). PMID- 9984193 TI - Normal-state magnetotransport in superconducting Tl2Ba2CuO6+ delta to millikelvin temperatures. PMID- 9984194 TI - Influence of rare-earth ionic radius on the properties of Ni- and Fe-substituted RBa2(Cu1-xMx)3O7-y systems (R=Y,Nd,Eu,Gd,Ho,Tm; M=Ni,Fe). PMID- 9984195 TI - Surface boundary conditions for the Ginzburg-Landau theory of d-wave superconductors. PMID- 9984196 TI - Theoretical study of Cu-O chain fragments in the oxygen-deficient planes of YBa2Cu3O6+x. I. Microscopic properties. PMID- 9984197 TI - Theoretical study of Cu-O chain fragments in the oxygen-deficient planes of YBa2Cu3O6+x. II. Intrachain interactions and the chain fragment's length distribution. PMID- 9984198 TI - Effects of gap and band anisotropy on spin susceptibility in the oxide superconductors. PMID- 9984199 TI - Effect of cobalt doping on thermal conductivity of YBa2Cu3O7- delta superconductor. PMID- 9984200 TI - 63Cu(2) nuclear quadrupole and nuclear magnetic resonance studies of YBa2Cu4O8 in the normal and superconducting states. PMID- 9984201 TI - Knight shift and spin-echo decay time of YBa2Cu4O8 and YBa2Cu3O7 in the superconducting state. PMID- 9984202 TI - Sign reversal of the Hall effect in superconducting YBa2(Cu1-xNix)3O7- delta single crystals. PMID- 9984204 TI - Pairing correlations in two-dimensional large-size Cu-O clusters: Nonlocal world line Monte Carlo algorithm. PMID- 9984203 TI - Vortex state of a d-wave superconductor in high-Tc cuprates. PMID- 9984205 TI - Transport properties of Pb-doped Bi4Sr3Ca3Cu4Ox semiconducting glasses and glass ceramic superconductors. PMID- 9984206 TI - Erratum: Thermal formation of vacancies in Fe3Si PMID- 9984207 TI - Fluctuation formula for elastic constants. PMID- 9984208 TI - Equation of state of cobalt up to 79 GPa. PMID- 9984209 TI - Interpretation of the analysis of Frenkel exciton fluorescence. PMID- 9984210 TI - Tight-binding study of interaction time in molecular switches. PMID- 9984211 TI - High-pressure Raman scattering of the stretching mode in nitrogen along the 300-K isotherm. PMID- 9984212 TI - Capillary condensation, invasion percolation, hysteresis, and discrete memory. PMID- 9984214 TI - Magnetic moment in Ni clusters estimated by an electronic-shell model. PMID- 9984213 TI - Explanation for the temperature dependence of plasma frequencies in SrTiO3 using mixed-polaron theory. PMID- 9984215 TI - Exact solution of a two-chain model of fermions. PMID- 9984216 TI - Spin-density fluctuation in paramagnets. PMID- 9984217 TI - Magnetotransport properties of SrRuO3 epitaxial thin films on (100) LaAlO3: Presence of localized magnetic moments. PMID- 9984218 TI - Quantum integrability for the one-dimensional Hubbard open chain. PMID- 9984219 TI - Magnetic excitation in the Hubbard-Hirsch model. PMID- 9984220 TI - Specific heat of UPd2Au3: Evidence for an unusual heavy-fermion state. PMID- 9984222 TI - Large enhancement of the perpendicular giant magnetoresistance in pseudorandom magnetic multilayers. PMID- 9984221 TI - Giant moment of Fe16N2 as evidenced by 57Fe NMR studies. PMID- 9984223 TI - Ruderman-Kittel interaction in one dimension for arbitrary coupling constant. PMID- 9984224 TI - Torque method for the theoretical determination of magnetocrystalline anisotropy. PMID- 9984225 TI - Scaling properties of spin-reorientation transitions in magnetic thin films with surface anisotropy. PMID- 9984226 TI - Two-magnon light scattering in Bi2CuO4. PMID- 9984227 TI - Low-field phase diagram of layered superconductors: The role of electromagnetic coupling. PMID- 9984228 TI - NMR relaxation rate in the superconducting state of the organic conductor kappa (BEDT-TTF)2Cu PMID- 9984230 TI - Vortex-glass-type transition in YBa2Cu3O7- delta ceramics. PMID- 9984229 TI - Spin-glass ordering of Fe-doped La2-xSrxCuO4. PMID- 9984231 TI - Iodine intercalation in Bi2Sr2Ca(Cu1-zCoz)2O8+ delta with different delta values. PMID- 9984232 TI - Instability of the local charge-density-wave potential energy for BaBiO3- delta. PMID- 9984233 TI - Temperature dependence of the sublattice magnetization of the antiferromagnet Ca0.85Sr0.15CuO2. PMID- 9984234 TI - Evidence of apical oxygen in artificially superconducting SrCuO2-BaCuO2 thin films: A Raman characterization. PMID- 9984235 TI - Angular dependence of the artificially induced anistropy in a-axis-oriented EuBa2Cu3O7/PrBa2Cu3O7 superconducting superlattices. PMID- 9984236 TI - Femtosecond studies of the phase transition in Ti2O3. PMID- 9984237 TI - Structure, dynamics, and phase transitions in the fullerene derivatives C60O and C61H2. PMID- 9984238 TI - Tight-binding study of tilt grain boundaries in diamond. PMID- 9984239 TI - Model for radiation-induced electrical degradation of alpha -Al2O3 crystals. PMID- 9984240 TI - Raman scattering from boron-substituted carbon films. PMID- 9984241 TI - Irreversible structural changes in vitreous B2O3 under pressure. PMID- 9984242 TI - Polarized x-ray-absorption spectroscopy of the uranyl ion: Comparison of experiment and theory. PMID- 9984243 TI - Monte Carlo study of the domain growth in nonstoichiometric two-dimensional binary alloys. PMID- 9984245 TI - Electrical conductivity relaxation and nuclear magnetic resonance of Li conducting Li0.5La0.5TiO3. PMID- 9984244 TI - Many-body atomistic model potential for intermetallic compounds and alloys and its application to NiAl. PMID- 9984246 TI - Structure, dynamics, and electronic structure of liquid Ag-Se alloys investigated by ab initio simulation. PMID- 9984248 TI - Multiple Bragg diffraction in quasicrystals: The issue of centrosymmetry in Al-Pd Mn. PMID- 9984247 TI - Phonon attenuation in amorphous solids studied by picosecond ultrasonics. PMID- 9984250 TI - Universality class in the one-dimensional localization problem. PMID- 9984249 TI - Correlation of temperature dependence of quasielastic-light-scattering intensity and alpha -relaxation time. PMID- 9984251 TI - Onset of fragment formation in periodic expanding systems. PMID- 9984253 TI - Transmission of double-impurity atomic switches. PMID- 9984252 TI - Anomalous temperature dependence of the first diffraction peak in vitreous boron trioxide. PMID- 9984255 TI - Supersonic mechanisms for charge and energy transfers in anharmonic molecular chains. PMID- 9984254 TI - Isotopic anomaly in dimer emission from alloy liquid-metal-ion-source mass spectroscopy. PMID- 9984256 TI - Bounding of effective thermal conductivities of multiscale materials by essential and natural boundary conditions. PMID- 9984257 TI - Temperature dependence of the phonon broadening of the Si 2p XPS line. PMID- 9984258 TI - Vibrational analysis of wadeite K2ZrSi3O9 and comparisons with benitoite BaTiSi3O9. PMID- 9984259 TI - Inelastic x-ray scattering from TiC and Ti single crystals. PMID- 9984261 TI - Mobility and diffusivity in a generalized Frenkel-Kontorova model. PMID- 9984260 TI - Solitonic-exchange mechanism of surface diffusion. PMID- 9984262 TI - Second sound and characteristic temperature in solids. PMID- 9984263 TI - Transient Fourier-law deviation by molecular dynamics in solid argon. PMID- 9984264 TI - Elastic properties of superconducting Chevrel-phase compounds. PMID- 9984265 TI - Magnetic phase diagram of a partially frustrated triangular antiferromagnet: The row model. PMID- 9984266 TI - Eliminating metastability in first-order phase transitions. PMID- 9984267 TI - High-temperature expansion study of the Nishimori multicritical point in two and four dimensions. PMID- 9984268 TI - Success and failure of the Friedel-Anderson resonance model for magnetic impurities: 3d impurities on the surface of Au. PMID- 9984269 TI - Magnetic linear and circular dichroism in core-level photoemission and magnetic circular x-ray dichroism in absorption for ultrathin films Fe/Pd(100). PMID- 9984270 TI - Simulation of spin diffusion in a disordered system. PMID- 9984271 TI - Quantum decay of metastable states in small magnetic particles. PMID- 9984272 TI - Ground state of an antiferromagnetic Heisenberg spin system on a nontranslational lattice of dimension between one and two. PMID- 9984274 TI - 19F NMR study of KMnFeF6: A frustrated magnetic system. PMID- 9984273 TI - Magnetization studies of type-II antiferromagnetic EuTe/PbTe superlattices. PMID- 9984275 TI - Experimental study of the structural and magnetic properties of Fe/Tb multilayers. PMID- 9984277 TI - Theory of nonreciprocal optical effects in antiferromagnets: The case of Cr2O3. PMID- 9984276 TI - Specific heat below 1 mK and the electric-field gradient in indium. PMID- 9984278 TI - Structural and magnetic properties of metastable fcc Cu-Fe alloys. PMID- 9984279 TI - Low-temperature transport of magnetic excitons in the quasi-one-dimensional antiferromagnet CsMnCl3 PMID- 9984280 TI - ac susceptibility of Rb3C60 fine powder. PMID- 9984281 TI - Anomalous magnetization behavior of single-crystalline CeRu2. PMID- 9984282 TI - Infrared investigation of the broken-symmetry ground state in GeCuO3. PMID- 9984283 TI - Effect of anisotropy on magneto-optical properties of uniaxial crystals: Application to CrO2. PMID- 9984285 TI - Microwave response of superconducting platelet crystals. PMID- 9984284 TI - Analysis of angularly dependent ODNMR spectra of 151Eu3+ in LaF3. PMID- 9984286 TI - Critical behavior of the flux-line tension in extreme type-II superconductors. PMID- 9984287 TI - Interaction between a two-dimensional pancake vortex and a circular nonsuperconducting defect. PMID- 9984288 TI - Photoemission study of Ni borocarbides: Superconducting YNi2B2C and nonsuperconducting LaNi2B2C. PMID- 9984289 TI - Magnetic-coherence-length scaling in metallic multilayers. PMID- 9984291 TI - Phonon amplification using evaporation and adsorption of helium. PMID- 9984290 TI - Langevin simulations of two-dimensional vortex fluctuations: Anomalous dynamics and IV exponent. PMID- 9984292 TI - 199Hg and 63Cu NMR in superconducting HgBa2CuO4+ delta oriented powder. PMID- 9984294 TI - Ground state and excitations of the supersymmetric extended Hubbard model with long-range interaction. PMID- 9984293 TI - Phase separation and oxygen diffusion in electrochemically oxidized La2CuO4+ delta : A static magnetic susceptibility study. PMID- 9984295 TI - Josephson tunneling in high-Tc superconductors. PMID- 9984296 TI - Theory of photoemission in the Hubbard model for Bi2Sr2CaCu2O8. PMID- 9984297 TI - Dynamical exponents for the current-induced percolation transition in high-Tc superconductors. PMID- 9984299 TI - Cooperative flux pinning in single crystals of YBa2Cu3O7- delta. PMID- 9984298 TI - Monte Carlo studies of the ordering of ceramic superconductors: Chiral-glass, orbital-glass, and nonlinear susceptibilities. PMID- 9984300 TI - Anisotropy in the irreversible behavior of pointlike defects and twins in YBa2Cu3O7- delta single crystals with a peak effect. PMID- 9984301 TI - Accommodation of vortices to tilted line defects in high-Tc superconductors with various electronic anisotropies. PMID- 9984302 TI - High-frequency vortex response of anisotropic type-II superconductors. PMID- 9984303 TI - Vortex solid-to-liquid transition in DyBa2Cu3O7- delta /(Y0.45Pr0.55)Ba2Cu3O7- delta multilayers. PMID- 9984304 TI - Gas effusion spectra of HgBa2CuO4+ delta. PMID- 9984305 TI - Length-scale-dependent layer decoupling and critical fluctuations in high temperature superconductors. PMID- 9984306 TI - Role of out-of-plane copper orbitals in thallium cuprate. PMID- 9984307 TI - Quasiparticle damping and the coherence peak in YBa2Cu3O7- delta. PMID- 9984309 TI - Erratum: Model for the glass transition in amorphous solids based on fragmentation PMID- 9984308 TI - Erratum: Dynamical properties of the single-hole t-J model on a 32-site square lattice PMID- 9984310 TI - Multicritical point in structurally incommensurate PMID- 9984311 TI - Anharmonic interatomic potentials of octahedral Pt-halogen complexes studied by extended x-ray-absorption fine structure. PMID- 9984313 TI - Atomistic simulation of ideal shear strength, point defects, and screw dislocations in bcc transition metals: Mo as a prototype. PMID- 9984312 TI - Near-neighbor mixing and bond dilation in mechanically alloyed Cu-Fe. PMID- 9984314 TI - Vibrational and electronic absorption study of bistable and stable FH(OH-) centers in alkali halides. PMID- 9984315 TI - Electronic-vibrational energy transfer between F centers and OH- impurities in KBr studied by Stokes and anti-Stokes Raman scattering. PMID- 9984316 TI - Electronic, vibrational, and configurational relaxation of the FH(OH-) center in KBr. PMID- 9984317 TI - Electron-paramagnetic-resonance measurements on the di-<001>-split interstitial center (R1) in diamond. PMID- 9984318 TI - ? PMID- 9984319 TI - Theoretical study of shear-modulus instabilities in the alkali metals under hydrostatic pressure. PMID- 9984321 TI - Simple equation of state for solids under compression. PMID- 9984320 TI - Pressure-induced disordering of sodium potassium sulfates and chromates. PMID- 9984322 TI - Melting of classical two-dimensional electrons on a helium film: A molecular dynamics study. PMID- 9984323 TI - Pressure-induced structural phase transitions in the AMnF4 series (A=Cs, Rb, K) studied by synchrotron x-ray powder diffraction: Correlation between hydrostatic and chemical pressure. PMID- 9984324 TI - Effect of the local electronic temperature on secondary-ion spectra. PMID- 9984325 TI - Structural changes in diamond and amorphous carbon induced by low-energy ion irradiation. PMID- 9984326 TI - Analysis of dissipation of a burst-type martensite transformation in a Fe-Mn alloy by internal friction measurements. PMID- 9984327 TI - First-principles determination of the tensile and slip energy barriers for B2 NiAl and FeAl. PMID- 9984329 TI - Bonding and electronic structure in zirconia pseudopolymorphs investigated by electron energy-loss spectroscopy. PMID- 9984328 TI - Order-disorder phase transition in p-chloronitrobenzene studied by NQR and DTA. PMID- 9984330 TI - Short-range order in linear binary alloys: Delocalization of states versus memory of ordered band structures. PMID- 9984332 TI - Dynamics of quadrupolar glasses. PMID- 9984331 TI - Long-range correlations in nonequilibrium quantum Lorentz gases. PMID- 9984333 TI - Microbranching instability and the dynamic fracture of brittle materials. PMID- 9984334 TI - Band theory of induced magnetic moments in CoM (M=Rh, Ru) alloys. PMID- 9984335 TI - Temperature dependence of positron-annihilation lifetime, free volume, conductivity, ionic mobility, and number of charge carriers in a polymer electrolyte polyethylene oxide complexed with NH4ClO4. PMID- 9984337 TI - Dynamical Jahn-Teller effect and Berry phase in positively charged fullerenes: Basic considerations. PMID- 9984336 TI - Shell-model lattice dynamics and Mossbauer recoilless fraction of SnO. PMID- 9984338 TI - Critical properties of the one-dimensional spin-1/2 antiferromagnetic Heisenberg model in the presence of a uniform field. PMID- 9984339 TI - Universality class of O(N) models. PMID- 9984340 TI - Electronic and magnetic structure of LaCuO2.5. PMID- 9984341 TI - Frustrated pyrochlore oxides, Y2Mn2O7, Ho2Mn2O7, and Yb2Mn2O7: Bulk magnetism and magnetic microstructure. PMID- 9984342 TI - Commensurate and incommensurate magnetic structures of UNiGe. PMID- 9984344 TI - X-ray magnetic scattering study of three-dimensional magnetic order in the quasi one-dimensional antiferromagnet Nd2BaNiO5. PMID- 9984343 TI - Magnetic gap excitations in a one-dimensional mixed spin antiferromagnet Nd2BaNiO5. PMID- 9984345 TI - Magnetic excitations in the itinerant ferromagnet UFe2. PMID- 9984347 TI - Spin dynamics of chromium. II. Incommensurate alloys. PMID- 9984346 TI - Spin dynamics of chromium. I. Formalism and commensurate alloys. PMID- 9984349 TI - Two-dimensional spin fluctuations of Ho3+ in HoBa2Cu3O7. PMID- 9984348 TI - Synchrotron x-ray-scattering study of magnetic-field-induced transitions in Cu1 x(Zn, Ni)xGeO3. PMID- 9984350 TI - Static computational micromagnetism of demagnetization processes in nanoscaled permanent magnets. PMID- 9984351 TI - Ising spin glass: Replica-symmetric cluster expansion in finite dimensions. PMID- 9984352 TI - Strong-coupling analysis of two-dimensional O(N) sigma models with N <~ 2 on square, triangular, and honeycomb lattices. PMID- 9984353 TI - Phonons in pure and doped CuGeO3 spin-Peierls crystals: Raman and ultrasonic studies. PMID- 9984355 TI - Electronic and magnetic states in the giant magnetoresistive compounds. PMID- 9984354 TI - Identification of molybdenum in 6H-SiC by magnetic resonance techniques. PMID- 9984357 TI - Contact angle of liquid He mixtures on Cs: Evidence for 3He at the He-Cs interface. PMID- 9984356 TI - Multiple-scattering theory of x-ray magnetic circular dichroism: Implementation and results for the iron K edge. PMID- 9984358 TI - Bound states and Josephson current in mesoscopic s-wave superconductor-normal metal-d-wave superconductor junctions. PMID- 9984360 TI - Hamiltonian approach to the transport properties of superconducting quantum point contacts. PMID- 9984359 TI - Static and dynamic processes in a two-dimensional Josephson junction. PMID- 9984361 TI - Charge representation of a small two-dimensional Josephson-junction array in the quantum regime. PMID- 9984363 TI - Response of liquid 3He at finite temperatures. PMID- 9984362 TI - Magnetization of multiple-quanta vortex lattices. PMID- 9984364 TI - Electrical resistivity of UBe13 in high magnetic fields. PMID- 9984366 TI - Charge transport in voltage-biased superconducting single-electron transistors. PMID- 9984365 TI - Diagrammatic theory of random scattering matrices for normal-metal superconducting mesoscopic junctions. PMID- 9984367 TI - Hall effect in the two-dimensional metal Sr2RuO4. PMID- 9984368 TI - Electron scattering from interacting tunneling units: A model for high-Tc superconductivity. PMID- 9984369 TI - Pair breaking by impurities in the two-dimensional t-J model. PMID- 9984370 TI - Temperature dependence of the in-plane resistivity in underdoped Bi2Sr2CaCu2Oy single crystals. PMID- 9984371 TI - Crystal growth and anisotropic resistivity of Bi2Sr2-xLaxCuOy. PMID- 9984372 TI - Effect of oxygen content on the anomalies at successive phase transitions of La2CuO4+ delta single crystal below 320 K. PMID- 9984373 TI - Experimental investigation of the pairing state of high-temperature superconductors. PMID- 9984374 TI - Fluctuation-induced in-plane conductivity, magnetoconductivity, and diamagnetism of Bi2Sr2CaCu2O8 single crystals in weak magnetic fields. PMID- 9984375 TI - Variation of the in-plane penetration depth lambda ab as a function of doping in La2-xSrxCuO4+/- delta thin films on SrTiO3: Implications for the overdoped state. PMID- 9984376 TI - Neutron-scattering study of stripe-phase order of holes and spins in La1.48Nd0.4Sr0.12CuO4. PMID- 9984377 TI - Superconducting-plasma resonance along the c axis in various copper oxide superconductors. PMID- 9984378 TI - Comparative study of the characteristic length scales and fields of Hg-based high Tc superconductors. PMID- 9984380 TI - Linewidth of c-axis plasma resonance in Josephson-coupled superconductors. PMID- 9984379 TI - Growth, microstructure, and electrochemical oxidation of MBE-grown c-axis La2CuO4 thin films. PMID- 9984381 TI - ac susceptibility of high-temperature superconductors. PMID- 9984383 TI - NMR and neutron-scattering experiments on the cuprate superconductors: A critical re-examination. PMID- 9984382 TI - Low-temperature ordering in YBa2Cu3O6+x oxides at x>0.5: Computer simulation. PMID- 9984384 TI - Infrared absorption in silicon from shallow thermal donors incorporating hydrogen and a link to the NL10 paramagnetic resonance spectrum. PMID- 9984385 TI - Microscope models of guest molecular vibrations in crystalline and glass hosts. PMID- 9984386 TI - Quantum effects in the dynamics of proton glasses. PMID- 9984387 TI - Diffusion of 54Mn and 59Fe in icosahedral Al-Pd-Mn single quasicrystals. PMID- 9984388 TI - Electronic Hamiltonian for transition-metal oxide compounds. PMID- 9984389 TI - Magnetic coupling in metallic granular systems. PMID- 9984390 TI - Y2BaNiO5: A nearly ideal realization of the S=1 Heisenberg chain with antiferromagnetic interactions. PMID- 9984391 TI - Observation of S=1 fractional spins in the S=2 finite linear-chain Heisenberg antiferromagnet CsCr1-xMgxCl3. PMID- 9984392 TI - New phase diagram of Zn-doped CuGeO3. PMID- 9984393 TI - Molecular spin ladder in the Ni(dmit)2 (dmit=1,3-dithiol-2-thione-4,5-dithiolate) salt with a nitronyl nitroxide cation. PMID- 9984395 TI - Longitudinal current dissipation in Bose-glass superconductors. PMID- 9984394 TI - Magnetoresistance scaling in MBE-grown La0.7Ca0.3MnO3 thin films. PMID- 9984396 TI - Viscosity measurements in normal and superfluid 3He. PMID- 9984398 TI - Cooper-pair charge solitons: The electrodynamics of localized charge in a superconductor. PMID- 9984397 TI - Double-resonance NMR probes of structural distortions in alkali-metal-fulleride superconductors. PMID- 9984399 TI - Determination of 13C NMR isotropic Knight shift and deviation from BCS relation in A3C60 superconductors. PMID- 9984400 TI - High-resolution thermal expansion of superconducting fullerides A3C60 (A=K,Rb). PMID- 9984401 TI - Monte Carlo study of a three-dimensional vortex-glass model with screening. PMID- 9984402 TI - Influence of a magnetic field on the antiferromagnetic order in UPt3. PMID- 9984404 TI - Evidence of the temperature-dependent interlayer coupling from the anisotropic transport properties in Co-substituted single-crystal Bi2Sr2Ca(Cu1-xCox)2O8+ delta. PMID- 9984403 TI - Density-of-states-driven anisotropies induced by momentum decoupling in Bi2Sr2CaCu2O8. PMID- 9984405 TI - Superconductivity fluctuation effects on the thermal conductivity of Bi2Sr2CaCu2O8. PMID- 9984406 TI - Emission of picosecond electromagnetic pulses from optically excited superconducting bridges. PMID- 9984407 TI - Observation of multiple peaks in the magnetization curves of NdBa2Cu3O7 single crystals. PMID- 9984408 TI - Impurity scattering and localization in d-wave superconductors. PMID- 9984409 TI - Influence of oxygen-ordering kinetics on Raman and optical response in YBa2Cu3O6.4. PMID- 9984410 TI - High-frequency spin waves in YBa2Cu3O6.15. PMID- 9984411 TI - NMR evidence for common superconducting and pseudogap phase diagrams of YBa2Cu3O7 delta and La2-xSrxCaCu2O6. PMID- 9984412 TI - Analytical expression for the optimized stop bands of fcc photonic crystals in the scalar-wave approximation. PMID- 9984414 TI - Adaptive finite-element method for electronic-structure calculations. PMID- 9984413 TI - Symmetrized density-matrix renormalization-group method for excited states of Hubbard models. PMID- 9984415 TI - Enhancement of the Kondo temperature of magnetic impurities in metallic point contacts due to the fluctuations of the local density of states. PMID- 9984416 TI - Shallow and deep traps in conjugated polymers of high intrachain order. PMID- 9984417 TI - Spin susceptibility and magnetic short-range order in the Hubbard model. PMID- 9984418 TI - Structural and vibrational properties of complexes formed by hydrogen and As antisites in gallium arsenide. PMID- 9984419 TI - Cathodoluminescence and photoinduced current spectroscopy studies of defects in Cd0.8Zn0.2Te. PMID- 9984420 TI - Jahn-Teller effect in ZnS:Fe2+ revisited with a modified Lanczos-type algorithm. PMID- 9984421 TI - Thermopower and conductivity activation energies in hydrogenated amorphous silicon. PMID- 9984422 TI - EPR study of the hyperfine structure of Yb3+ ion in Pb1-xYbxS, Pb1-xYbxSe, and Pb1-xYbxTe single crystals. PMID- 9984423 TI - Smooth monolayer As- and Ga-terminated GaAs(100) surfaces. PMID- 9984424 TI - Green's function of a two-dimensional interacting electron gas in a perpendicular magnetic field. PMID- 9984425 TI - Temperature and excitation intensity dependencies of the photoluminescence spectra of GaAs/(AlGa)As disordered superlattices. PMID- 9984427 TI - Direct manifestation of the Fermi pressure in a two-dimensional electron system. PMID- 9984426 TI - Drift current and thermal pressure effects in the electromagnetic instabilities of periodic semiconductor superlattices. PMID- 9984428 TI - Quantum-group treatment of substrate potential in the integer quantum Hall effect. PMID- 9984430 TI - Saturation of the internal photoemission effect in forward biased silicon junctions. PMID- 9984429 TI - Low-temperature electron mobility in a real delta -doped semiconductor. PMID- 9984431 TI - Electronic structure of semiconductor quantum wells in a tilted magnetic field. PMID- 9984432 TI - Tunneling calculations for systems with singular coupling matrices: Results for a simple model. PMID- 9984433 TI - Frozen electron solid in the presence of small concentrations of defects. PMID- 9984434 TI - Oscillator strengths for optical band-to-band processes in GaN epilayers. PMID- 9984435 TI - Type-II interface exciton in ZnSe/(Zn,Mn)Se heterostructures. PMID- 9984436 TI - Si 2p core-level shifts at the Si(100)-SiO2 interface: An experimental study. PMID- 9984437 TI - Shapes of 3He clusters. PMID- 9984438 TI - Hexagonal phase with mosaic structure of charge-density waves observed by scanning tunneling microscopy at the surface of a NbSe3 crystal. PMID- 9984440 TI - Adsorption and desorption kinetics of CO on Cu(110) studied by optical differential reflectance. PMID- 9984439 TI - Adhesive energy and charge transfer for MgO/Cu heterophase interfaces. PMID- 9984441 TI - Initial growth of insulating overlayers of NaCl on Ge(100) observed by scanning tunneling microscopy with atomic resolution. PMID- 9984442 TI - Nucleation and growth of Si/Si(111) observed by scanning tunneling microscopy during epitaxy. PMID- 9984444 TI - Nonlocal screening effects in 2p x-ray photoemission spectroscopy of NiO (100). PMID- 9984443 TI - Surface-induced broadening of photoemission core levels. PMID- 9984445 TI - Theory of the Seebeck coefficient in LaCrO3 and related perovskite systems. PMID- 9984446 TI - Spherical self-consistent atomic deformation model for first-principles energy calculations in ionic crystalline solids. PMID- 9984447 TI - Composite quasiparticle formation and the low-energy effective Hamiltonians for the one- and two-dimensional Hubbard model. PMID- 9984448 TI - Self-consistent GW and higher-order calculations of electron states in metals. PMID- 9984449 TI - Path-integral analysis of the exchange-correlation energy and potential in density-functional theory: Unpolarized systems. PMID- 9984451 TI - Vacancies, interstitials, and close Frenkel pairs on the zinc sublattice of ZnSe. PMID- 9984450 TI - Metal-insulator transitions due to self-doping. PMID- 9984452 TI - Exchange and radiative lifetimes for close Frenkel pairs on the zinc sublattice of ZnSe. PMID- 9984453 TI - Electronic properties of TiSi2 single crystals at low temperatures. PMID- 9984454 TI - Photoemission study of electronic structures of disordered Ni-Pt and Cu-Pt alloys. PMID- 9984455 TI - Electronic structure of La1-xSrxCrO3. PMID- 9984457 TI - Infrared intensities and Raman-scattering activities within density-functional theory. PMID- 9984456 TI - Excited states in metal voids. PMID- 9984458 TI - Microcavities in photonic crystals: Mode symmetry, tunability, and coupling efficiency. PMID- 9984459 TI - Point-charge electrostatics in disordered alloys. PMID- 9984460 TI - First-principles study of titanium oxides. PMID- 9984461 TI - Thermodynamics of the Falicov-Kimball model. PMID- 9984462 TI - Nitrogen-related dopant and defect states in CVD diamond. PMID- 9984463 TI - Hydrogen-related defects in polycrystalline CVD diamond. PMID- 9984464 TI - Optimized effective-potential calculations of Ge and GaAs. PMID- 9984465 TI - Fe, Ru, and Os disilicides: Electronic structure of ordered compounds. PMID- 9984466 TI - Metastable defect complexes in GaAs. PMID- 9984467 TI - Electric and magnetic dipole two-photon absorption in semiconductors. PMID- 9984468 TI - Resonant Raman scattering probe of alloying effect in GaAs1-xPx ternary alloy semiconductors. PMID- 9984469 TI - Picosecond and millisecond dynamics of photoexcited carriers in porous silicon. PMID- 9984471 TI - Electronic conduction above 4 K of slightly reduced oxygen-deficient rutile TiO2 x. PMID- 9984470 TI - Real-space Green's-function approach applied to the phonon spectra of isolated impurities. PMID- 9984473 TI - Effects of quantum fluctuations of electrons and lattice in doped polyacetylene. PMID- 9984472 TI - Carrier transport in amorphous silicon-based thin-film transistors studied by spin-dependent transport. PMID- 9984474 TI - Donor activation and electronic screening at an antimony delta layer in silicon. PMID- 9984476 TI - Simulation studies of photon-assisted quantum transport. PMID- 9984475 TI - Analysis of capacitance-voltage characteristics of Si1-xGex/Si quantum-well structures. PMID- 9984477 TI - Electronic structure of a Si delta -doped layer in a GaAs/AlxGa1-xAs/GaAs quantum barrier. PMID- 9984479 TI - Quantum interference effects in antidot lattices in magnetic fields. PMID- 9984478 TI - Carrier-carrier scattering in the gain dynamics of InxGa1-xAs/AlyGa1-yAs diode lasers. PMID- 9984480 TI - First-principles studies of hydrogenated Si(111)-7 x 7. PMID- 9984481 TI - Exchange-correlation energy for a two-dimensional electron gas in a magnetic field. PMID- 9984482 TI - Electronic transport in quantum wires in nonuniform magnetic fields. PMID- 9984483 TI - Theoretical study on commensurability oscillation in anisotropic antidot lattices. PMID- 9984484 TI - Plasmon-pole approximation for semiconductor quantum-wire electrons. PMID- 9984485 TI - Separation of the sp3 and sp2 components in the C1s photoemission spectra of amorphous carbon films. PMID- 9984486 TI - Comparison of self-consistency iteration options for the Wigner function method of quantum device simulation. PMID- 9984487 TI - Exciton-polariton ladder in a semiconductor microcavity. PMID- 9984488 TI - Mechanisms for optical nonlinearities and ultrafast carrier dynamics in CuxS nanocrystals. PMID- 9984489 TI - Thermodynamics of a one-dimensional lattice system with long-range interelectron repulsion. PMID- 9984490 TI - Persistent current in disordered Aharonov-Bohm rings with interacting electrons. PMID- 9984491 TI - Generalized eigenproblem method for surface and interface states: The complex bands of GaAs and AlAs. PMID- 9984492 TI - Electric field effects on excitons in gallium nitride. PMID- 9984493 TI - Dynamic response of a two-dimensional electron gas: Effect of short-range correlations in the ladder approximation. PMID- 9984495 TI - Distribution of transmitted charge through a double-barrier junction. PMID- 9984494 TI - Dynamic admittance of mesoscopic conductors: Discrete-potential model. PMID- 9984496 TI - Diffuse scattering from interface roughness in grazing-incidence x-ray diffraction. PMID- 9984497 TI - Growth of Ag on Cu(100) studied by STM: From surface alloying to Ag superstructures. PMID- 9984498 TI - Direct reconstruction of three-dimensional atomic adsorption sites by holographic LEED. PMID- 9984500 TI - Calculation of the dielectric constant of monolayer films on a material surface. PMID- 9984499 TI - Localization phenomena in elastic surface-polariton scattering caused by surface roughness. PMID- 9984501 TI - Dielectric behavior of organic monolayers due to orientational phase transition. PMID- 9984502 TI - Buckled reconstruction of the alkali-metal (Na, K)-adsorbed Si(111)-(3 x 1) surfaces. PMID- 9984503 TI - Ab initio theory of surface segregation: Self-consistent determination of the concentration profile. PMID- 9984505 TI - Statistics of three-dimensional island growth for a reactive interface: Ni/GaAs(110). PMID- 9984504 TI - Membranes on rough self-affine surfaces. PMID- 9984506 TI - Plasma instabilities in a steady-state nonequilibrium one-dimensional solid-state plasma of finite length. PMID- 9984508 TI - Interactions of hydrogen and methyl radicals with diamond C(111) studied by sum frequency vibrational spectroscopy. PMID- 9984507 TI - Optical properties of self-affine thin films. PMID- 9984509 TI - Friction on adsorbed monolayers. PMID- 9984510 TI - Erratum: High-current ballistic transport through variable-width constrictions in a high-mobility two-dimensional electron gas PMID- 9984511 TI - Pseudopotential variational quantum Monte Carlo approach to bcc lithium. PMID- 9984513 TI - Self-consistent GW0 results for the electron gas: Fixed screened potential W0 within the random-phase approximation. PMID- 9984512 TI - Simple analytical embedded-atom-potential model including a long-range force for fcc metals and their alloys. PMID- 9984514 TI - Investigation of density functionals to predict both ground-state properties and band structures. PMID- 9984515 TI - Algebraic Bethe ansatz for the supersymmetric U model. PMID- 9984516 TI - Electronic structure of the quasi-one-dimensional halogen-bridged Ni complexes PMID- 9984517 TI - Photoemission spectral weight distribution in Y1-xCaxTiO3. PMID- 9984518 TI - Transfer of spectral weight in spectroscopies of correlated electron systems. PMID- 9984519 TI - Anderson localization for two interacting electrons in a disordered chain. PMID- 9984520 TI - Anderson transition and critical level statistics in 2.58 dimensions. PMID- 9984522 TI - Collective transport through charge-density-wave heterostructures. PMID- 9984521 TI - Anisotropic electrical resistivity of ferromagnetic Co-Pd and Co-Pt alloys. PMID- 9984523 TI - Exact boundary critical exponents and tunneling effects in integrable models for quantum wires. PMID- 9984525 TI - Additional electromagnetic waves and stimulated light scattering in the vicinity of an excitonic resonance. PMID- 9984524 TI - Electronic structure of Al3Ni and AlNi3 alloys. PMID- 9984527 TI - Atomic structure of defect complexes containing carbon and hydrogen in GaAs. PMID- 9984526 TI - Effects of point defects on lattice parameters of semiconductors. PMID- 9984528 TI - Point defects and their reactions in electron-irradiated GaAs investigated by optical absorption spectroscopy. PMID- 9984530 TI - Spin-resonance determination of the electron effective g value of In0.53Ga0.47As. PMID- 9984529 TI - Polarization-dependent density-functional theory and quasiparticle theory: Optical response beyond local-density approximations. PMID- 9984531 TI - Anderson impurity in a semiconductor. PMID- 9984533 TI - Comparison between multiple trapping and multiple hopping transport in a random medium. PMID- 9984532 TI - Landau-like states in the magneto-optical spectrum of a shallow donor impurity: Theory versus experiment. PMID- 9984534 TI - Second-order Raman spectrum of AlSb from ab initio phonon calculations and evidence for overbending in the LO phonon branch. PMID- 9984535 TI - Displaced squeezed number states of the phonon field in polar semiconductors. PMID- 9984536 TI - Surface structure of the (3 x 1) and (3 x 2) reconstructions of Ge(113). PMID- 9984538 TI - Surface phonons of hydrogen-terminated semiconductor surfaces. III. Diamond (001) monohydride and dihydride. PMID- 9984537 TI - Influence of surfactant coverage on epitaxial growth of Ge on Si(001). PMID- 9984539 TI - Spontaneous coherence and collective modes in double-layer quantum-dot systems. PMID- 9984540 TI - Observation of a Cs-induced state in the band gap of GaP(110): Alkali-metal bonding and Fermi-level pinning. PMID- 9984541 TI - Two-photon transitions in systems with semiconductor quantum dots. PMID- 9984542 TI - Long-range resonance transfer of electronic excitations in close-packed CdSe quantum-dot solids. PMID- 9984544 TI - Collective and single-particle excitations of the quasi-one-dimensional electron gas in the presence of a magnetic field. PMID- 9984543 TI - Wigner crystallization in the lowest Landau level for nu >= 1/5. PMID- 9984545 TI - Transmission spectrum of a tunneling particle interacting with dynamical fields: Real-time functional-integral approach. PMID- 9984546 TI - Theory of arbitrarily polarized quantum Hall states: Filling fractions and wave functions. PMID- 9984547 TI - Direct test of the composite-fermion model in quantum Hall systems. PMID- 9984548 TI - Models for the integer quantum Hall effect: The network model, the Dirac equation, and a tight-binding Hamiltonian. PMID- 9984549 TI - Pressure dependence of the optic phonon energies in AlxGa1-xAs. PMID- 9984550 TI - Uniaxial-stress investigation of the phonon-assisted recombination mechanisms associated with the X states in type-II GaAs/AlAs superlattices. PMID- 9984552 TI - Eigenfunctions of electrons in weakly disordered quantum dots: Crossover between orthogonal and unitary symmetries. PMID- 9984551 TI - Electron-assisted exciton transfer and long-lived electrons and holes in GaAs/AlxGa1-xAs quantum wells. PMID- 9984554 TI - Model for diffusion and growth of silicon on Si(100) with inequivalent sites in a square lattice. PMID- 9984553 TI - Direct formation of vertically coupled quantum dots in Stranski-Krastanow growth. PMID- 9984555 TI - Scanning tunneling microscopy on Ga/Si(100). PMID- 9984556 TI - Strain and surface phenomena in SiGe structures. PMID- 9984557 TI - Lattice locations of silicon atoms in delta -doped layers in GaAs at high doping concentrations. PMID- 9984558 TI - Dephasing time of composite fermions. PMID- 9984560 TI - Optical absorption of wide quantum wires. PMID- 9984559 TI - Electronic structures and band offsets of heterocrystalline superlattices (3C AlN)3n/(2H-AlN)2n and (3C-SiC)3n/(2H-SiC)2n (n=1,2,3). PMID- 9984561 TI - Direct and indirect excitons in coupled GaAs/Al0.30Ga0.70As double quantum wells separated by AlAs barriers. PMID- 9984562 TI - Dynamic structure factor of a two-dimensional electron gas. PMID- 9984563 TI - Giant oscillations of acoustoelectric current in a quantum channel. PMID- 9984564 TI - Noise temperature of n+nn+ GaAs structures. PMID- 9984565 TI - Monolayer Kr films adsorbed on BN. PMID- 9984566 TI - GaAs equilibrium crystal shape from first principles. PMID- 9984568 TI - Energy transfer, trapping, and the interaction potential in hyperthermal Na+ scattering from Cu(001). PMID- 9984567 TI - Surface diffusion in the low-friction limit: Occurrence of long jumps. PMID- 9984569 TI - X-ray photoelectron-diffraction study of intermixing and morphology at the Ge/Si(001) and Ge/Sb/Si(001) interface. PMID- 9984570 TI - Potential, core-level, and d band shifts at transition-metal surfaces. PMID- 9984571 TI - Gibbs-Thomson formula for small island sizes: Corrections for high vapor densities. PMID- 9984572 TI - Imaging material properties by resonant tapping-force microscopy: A model investigation. PMID- 9984573 TI - Interpretation of photoelectron spectra in Cun - clusters including thermal and final-state effects: The case of Cu7 - PMID- 9984574 TI - Metastable states in hydrogenated amorphous carbon. PMID- 9984575 TI - Phase separation in the two-dimensional Hubbard model. PMID- 9984576 TI - Analytic continuation of the dynamic response function using an N-point Pade approximant. PMID- 9984578 TI - Gradient-corrected ab initio calculations of spin-spiral states in fcc-Fe and the effects of the atomic-spheres approximation. PMID- 9984577 TI - Magnetoresistance and magnetic breakdown in the quasi-two-dimensional conductors (BEDT-TTF)2MHg(SCN)4 PMID- 9984580 TI - Ultrafast high-energy luminescence in a high-electron-affinity conjugated polymer. PMID- 9984579 TI - Anomalous effective charges and far-IR optical absorption of Al2Ru from first principles. PMID- 9984581 TI - Coulomb enhancement of Faraday rotation in semimagnetic semiconductors. PMID- 9984583 TI - Dimer bond geometry in D/Ge(100)-(2 x 1): A low-energy electron-diffraction structure analysis. PMID- 9984582 TI - Inequivalent atoms and imaging mechanisms in ac-mode atomic-force microscopy of Si(111)7 x 7. PMID- 9984584 TI - Spin splitting in a polarized quasi-two-dimensional exciton gas. PMID- 9984585 TI - Anomalous features of resonant hyper-Raman scattering in CuBr quantum dots: Evidence of exciton-phonon-coupled states similar to molecules. PMID- 9984586 TI - Drift-velocity degradation caused by an electric field during collision in one dimensional quantum wires. PMID- 9984587 TI - Experimental determination of Gamma -X intervalley transfer mechanisms in GaAs/AlAs heterostructures. PMID- 9984588 TI - Hierarchy of relaxation times in the system of Mn-ion spins in photoexcited semimagnetic quantum wells. PMID- 9984589 TI - Anisotropic surface acoustic wave scattering in quantum-wire arrays. PMID- 9984591 TI - Magnetic properties of the Skyrmion gas in two dimensions. PMID- 9984590 TI - Coulomb gaps in one-dimensional spin-polarized electron systems. PMID- 9984592 TI - Electronic spectral functions for quantum Hall edge states. PMID- 9984593 TI - Electron-phonon heat transport in arrays of Al islands with submicrometer-sized tunnel junctions. PMID- 9984594 TI - Large magnetotunneling effect at low magnetic fields in micrometer-scale epitaxial La0.67Sr0.33MnO3 tunnel junctions. PMID- 9984596 TI - Green's-function approach to the optical nonlinearities in semiconductors and quantum-confined structures. PMID- 9984595 TI - Intrinsic band-edge photoluminescence from silicon clusters at room temperature. PMID- 9984597 TI - Photoinduced formation of dimers at a liquid/(001)GaAs interface. PMID- 9984598 TI - Raman scattering from acoustic phonons confined in Si nanocrystals. PMID- 9984599 TI - Electronic properties of carbon nanotubes with polygonized cross sections. PMID- 9984600 TI - Epitaxial growth and optical transitions of cubic GaN films. PMID- 9984601 TI - Nanostructural and local electronic properties of Fe/W(110) correlated by scanning tunneling spectroscopy. PMID- 9984603 TI - Isostructural phase transition in InN wurtzite. PMID- 9984602 TI - Electronic-structure effect on core-level excitation and charge transfer in ions scattering from alkali-metal-covered surfaces. PMID- 9984604 TI - Positron bound states on hydride ions in thermochemically reduced MgO single crystals. PMID- 9984605 TI - Effect of Cu ions on the polarization and polar lattice vibrations of potassium sodium strontium barium niobate single crystals. PMID- 9984606 TI - Experimental and theoretical determination of the metastable Fe-V phase diagram. PMID- 9984607 TI - Infrared absorption of solid nitrogen at high pressures. PMID- 9984608 TI - Theoretical structural phase stability of BeO to 1 TPa. PMID- 9984609 TI - Oxygen interstitials in magnesium oxide: A band-model study. PMID- 9984610 TI - Analyses of the ab initio harmonic interatomic force constants of stishovite. PMID- 9984611 TI - Intrinsic thermal-resistive process of crystals: Umklapp processes at low and high temperatures. PMID- 9984612 TI - Single-polaron band structure of the Holstein model. PMID- 9984613 TI - Statics and dynamics of charge fluctuations in the t-J model. PMID- 9984614 TI - Critical dynamics in layer-structured (C18H37NH3)2SnCl6. PMID- 9984615 TI - Charge localization by static and dynamic distortions of the MnO6 octahedra in perovskite manganites. PMID- 9984616 TI - Hall-effect sign reversal in CaRuO3 and SrRuO3 thin films. PMID- 9984617 TI - Long-ranged interacting S=1 spin chain with the exact valence-bond-solid state. PMID- 9984618 TI - Thermodynamical properties of the Heisenberg antiferromagnet on the kagome lattice. PMID- 9984619 TI - Valence-bond crystal phase of a frustrated spin-1/2 square-lattice antiferromagnet. PMID- 9984620 TI - Nagaoka state and degeneracy in the U= PMID- 9984621 TI - Magnetic neutron-scattering investigation of the field-induced Griffiths phase in FeCl2. PMID- 9984622 TI - Muon spin relaxation investigation of the spin dynamics of geometrically frustrated antiferromagnets Y2Mo2O7 and Tb2Mo2O7. PMID- 9984623 TI - Magnetic and electrical properties of the ferrimagnet Dy0.67Ca0.30MnO3+/-d. PMID- 9984624 TI - Spin-diffusion lengths of Cu1-xNix using current perpendicular to plane magnetoresistance measurements of magnetic multilayers. PMID- 9984625 TI - Magnetic structure of TmNi2B2C. PMID- 9984626 TI - Evaluation of individual atomic displacements in mixed atomic rows in Bi-Sr-Ca-Cu O by ion channeling. PMID- 9984627 TI - Theorem on pseudospin and eta -pairing superconductivity. PMID- 9984628 TI - Transverse ultrasound revisited: A directional probe of the A phase of UPt3. PMID- 9984629 TI - Fluxon-fluxon collision testing by a dissipative spot. PMID- 9984630 TI - Static properties of annular Josephson tunnel junctions. PMID- 9984631 TI - Phase separation in La2CuO4+ delta as probed by a paramagnetic surface defect. PMID- 9984632 TI - Spectral weight transfer in a doped strongly correlated insulator. PMID- 9984633 TI - Variational study of the spin-gap phase of the one-dimensional t-J model. PMID- 9984634 TI - Ordered states of substitutional cations in high-Tc superconducting systems. PMID- 9984635 TI - Observation of vortex-lattice melting in YBa2Cu3O7- delta by Seebeck-effect measurements. PMID- 9984636 TI - Local dynamics of YBa2Cu3O6+x and O(1)-defect dynamical stability. PMID- 9984638 TI - High-pressure EXAFS measurements of solid and liquid Kr. PMID- 9984637 TI - Temperature dependence of the elastic constants of LiKSO4 through a first-order structural phase transition. PMID- 9984639 TI - Structural, calorimetric, and Monte Carlo investigation of the order-disorder transition of BF4 in (CH 3)4NBF4. PMID- 9984640 TI - Thermodynamic model for solid-state amorphization in binary systems at interfaces and grain boundaries. PMID- 9984641 TI - Infrared-to-blue frequency upconversion in a Pr3+-doped silicate fiber. PMID- 9984642 TI - Hydrogen in Pd/Nb multilayers. PMID- 9984644 TI - Transferable atomistic model to describe the energetics of zirconia. PMID- 9984643 TI - 35Cl NQR in incommensurate bis(4-chlorophenyl) sulfone. PMID- 9984645 TI - ENDOR and pulsed ESR study of proton glass behavior in the mixed crystal (betaine phosphate)0.15(betaine phosphite)0.85. PMID- 9984646 TI - Magnetoresistance of Al90Y10 and Al90La10: Strong enhancement due to small crystalline precipitates in Al90La10. PMID- 9984647 TI - Photoluminescence in pyridine-based polymers: Role of aggregates. PMID- 9984648 TI - Mechanism of photoinduced anisotropy in chalcogenide glasses. PMID- 9984650 TI - Universal two-state reorientational dynamics of diatomic hydrides in fcc salt crystals. PMID- 9984649 TI - Phonon mechanism for the orthorhombic distortion in FeSi2 as compared to cubic CoSi2. PMID- 9984651 TI - Coherence tendencies in the transport of translationally invariant exciton-phonon systems. PMID- 9984653 TI - Nonlinear spin excitations in finite Heisenberg chains. PMID- 9984652 TI - Intermediate phase for a classical continuum model. PMID- 9984654 TI - Magnetic properties of ferrimagnetic binary-alloy Ising thin films. PMID- 9984655 TI - Magnetic properties of superparamagnetic particles by a Monte Carlo method. PMID- 9984656 TI - Dimer and Neel order-parameter fluctuations in the spin-fluid phase of the s=1/2 spin chain with first- and second-neighbor couplings. PMID- 9984657 TI - Low-density ferromagnetism in the Hubbard model. PMID- 9984658 TI - Magnetic phase diagram and magnetic structure of Gd(Sn1-xInx)3. PMID- 9984659 TI - Critical dynamics of the body-centered-cubic classical Heisenberg antiferromagnet. PMID- 9984660 TI - Static and dynamic response of cluster glass in La0.5Sr0.5CoO3. PMID- 9984661 TI - Magnetic resonance of type-I fcc antiferromagnets. PMID- 9984663 TI - Transitions in the direction of magnetism in Ni/Cu(001) ultrathin films and the effects of capping layers. PMID- 9984662 TI - Size-dependent magnetic properties of MnFe2O4 fine particles synthesized by coprecipitation. PMID- 9984664 TI - Magnetic moments in thin epitaxial Cr films on Fe(100). PMID- 9984665 TI - Photoluminescence-detected magnetic-resonance study of fullerene-doped pi conjugated polymers. PMID- 9984666 TI - Interface roughening in driven magnetic systems with quenched disorder. PMID- 9984667 TI - Ising-Kondo lattice with transverse field: A possible f-moment Hamiltonian for URu2Si2. PMID- 9984668 TI - Spin-density wave versus superconducting fluctuations for quasi-one-dimensional electrons in two chains of Tomonaga-Luttinger liquids. PMID- 9984670 TI - High-resolution angle-resolved photoemission spectroscopy of CeBi. PMID- 9984669 TI - Fermi-surface studies in the two-dimensional organic conductors (BEDT TTF)2MHg(SCN)4 (M=Tl,K,Rb,NH4). PMID- 9984672 TI - Emission of spin waves by a magnetic multilayer traversed by a current. PMID- 9984673 TI - Transport properties of L1-xSrxMnO3 (L=Pr, Nd; 1/4 <~ x <~ 1/2). PMID- 9984671 TI - Nonequilibrium orbital magnetization of strongly localized electrons. PMID- 9984674 TI - Analysis of scattering lengths in Co/Cu/Co and Co/Cu/Co/Cu spin-valves using a Ru barrier. PMID- 9984675 TI - Strong-coupling expansions for the anharmonic Holstein model and for the Holstein Hubbard model. PMID- 9984676 TI - Vortices in d-wave superconductors. PMID- 9984677 TI - Critical current of a quasi-one-dimensional superconducting wire. PMID- 9984678 TI - Superconducting properties of La3Ni2B2N3- delta. PMID- 9984679 TI - Magnetic and crystal-field properties of the magnetic superconductor DyNi2B2C from 161Dy Mossbauer spectroscopy. PMID- 9984681 TI - Macroscopic quantum tunneling in one-dimensional superconducting wires. PMID- 9984680 TI - Cross correlation of thermal flux noise in layered superconductors. PMID- 9984682 TI - Local density of states in a dirty normal metal connected to a superconductor. PMID- 9984684 TI - Pancake vortex near the sample surface. PMID- 9984683 TI - Flux flow and vortex tunneling in two-dimensional arrays of small Josephson junctions. PMID- 9984685 TI - Microscopic oscillations in the quantum nucleation of vortices subject to periodic pinning potential in a thin superconductor. PMID- 9984686 TI - Flux-line dynamics in YBa2Cu4O8 from 89Y NMR. PMID- 9984687 TI - Hall effect in moderately clean superconductors and the transverse force on a moving vortex. PMID- 9984688 TI - Asymmetric response of superconducting niobium-tunnel-junction x-ray detectors. PMID- 9984689 TI - Phase-coherent transport in hybrid superconducting structures: The case of d-wave superconductors. PMID- 9984691 TI - Superconducting instabilities of the non-half-filled Hubbard model in two dimensions. PMID- 9984690 TI - Comparison of critical and lowest-Landau-level scaling of the specific heat of several YBa2Cu3O7- delta single crystals. PMID- 9984692 TI - Interlayer tunneling in a strongly correlated electron-phonon system. PMID- 9984693 TI - Vortex lattice dynamics in DyBa2Cu3O7/(Sr1-xCax)RuO3 multilayers. PMID- 9984694 TI - Transport and NMR studies of the effect of Ni substitution on superconductivity and the normal-state pseudogap in YBa2Cu4O8. PMID- 9984695 TI - Magnetic behavior in Li-doped La2CuO4. PMID- 9984697 TI - Erratum: Strongly nonlinear composite dielectrics: A perturbation method for finding the potential field and bulk effective properties PMID- 9984696 TI - Comparison of local structure measurements from c-axis polarized XAFS between a film and a single crystal of YBa2Cu3O7- delta as a function of temperature. PMID- 9984698 TI - Erratum: Frustrated spin-Peierls chains PMID- 9984699 TI - Erratum: Quantum nucleation of magnetic bubbles PMID- 9984700 TI - Erratum: Molecular dynamics on a realistic model for a strong glass PMID- 9984701 TI - Characterization of strain in crystal bilayers using ion-channeling patterns. PMID- 9984702 TI - Ab initio simulations of tetrahedral amorphous carbon. PMID- 9984704 TI - OH-content dependence of fractoluminescence spectra in silica glass. PMID- 9984703 TI - Evidence for the occurrence of a prototype structure in Sc under pressure. PMID- 9984705 TI - Pressure-induced thermodynamic properties of atom-vacancy solid solution. PMID- 9984706 TI - Capillary-wave roughening of surface-induced layering in liquid gallium. PMID- 9984707 TI - Nucleation in disordered systems. PMID- 9984708 TI - First-principles study of multiple order-disorder transitions in Cd2AgAu Heusler alloys. PMID- 9984709 TI - Fragile-glass behavior of a short-range p-spin model. PMID- 9984710 TI - Embedded-atom interatomic potentials for hydrogen in metals and intermetallic alloys. PMID- 9984711 TI - Far-infrared spectra of alkali germanate glasses and correlation with electrical conductivity. PMID- 9984712 TI - Quantum lattice motion and optical absorption in conjugated polymers: Nonadiabatic theory. PMID- 9984713 TI - Stability of bipolarons in the presence of a magnetic field. PMID- 9984714 TI - Breathing self-localized solitons in the quartic Fermi-Pasta-Ulam chain. PMID- 9984715 TI - Dynamics of a charged particle in a magnetic-flux lattice. PMID- 9984716 TI - Demonstration of Avrami's kinetics: Connection with rate equations for clustering on surfaces. PMID- 9984717 TI - Observation of a magnetic-field-induced resonance in the homogeneous dephasing time for the 1D2-3H4 transition in Pr3+:YAlO3. PMID- 9984718 TI - Nonlinear resistivity and critical behavior of metal-overlayer percolation systems on epitaxial fullerene films. PMID- 9984719 TI - Theoretical study of the spin dynamics in CsNiF3, a one-dimensional ferromagnet with planar anisotropy, in an external magnetic field. PMID- 9984720 TI - Density-matrix renormalization-group study of S=1/2 Heisenberg spin chains: Friedel oscillations and marginal system-size effects. PMID- 9984721 TI - Dimerization and incommensurate spiral spin correlations in the zigzag spin chain: Analogies to the Kondo lattice. PMID- 9984722 TI - Antiferromagnetic interlayer correlations in annealed Ni80Fe20/Ag multilayers. PMID- 9984724 TI - Magnetic behavior in a series of cerium ternary intermetallics: Ce2T2In (T=Ni, Cu, Rh, Pd, Pt, and Au). PMID- 9984723 TI - Magnetic anisotropy in Fe/Cu(001) overlayers and interlayers: The high-moment ferromagnetic phase. PMID- 9984726 TI - Monte Carlo studies of the dynamics of reentrant Ising spin glasses. PMID- 9984725 TI - Dynamic magnetostatic interaction between amorphous ferromagnetic wires. PMID- 9984727 TI - Macroscopic quantum coherence of chirality of a domain wall in ferromagnets. PMID- 9984728 TI - Quantum theory of the coercive force and the capping effect for magnetic multilayers. PMID- 9984729 TI - Structure and enhanced magnetization in Fe/Pt multilayers. PMID- 9984730 TI - Oscillatory ferromagnetic interlayer coupling of Fe(110) thin films through (111) oriented Ag and Cu spacers. PMID- 9984732 TI - Magnetic-field and chemical-potential effects on the low-energy separation of the Hubbard chain. PMID- 9984731 TI - Nuclear-spin-lattice relaxation in natural clays via paramagnetic centers. PMID- 9984733 TI - Thermal properties at the low-temperature structural and magnetic phase transitions in Pr2NiO4 crystals. PMID- 9984735 TI - Spin-wave condensation and quantum melting of long-range antiferromagnetic order in the t-J model. PMID- 9984734 TI - Numerical model of quantum oscillations in quasi-two-dimensional organic metals in high magnetic fields. PMID- 9984736 TI - Spin-disorder scattering and localization in magnetoresistive (La1 xYx)2/3Ca1/3MnO3 perovskites. PMID- 9984737 TI - Mapping between multichannel exchange models. PMID- 9984738 TI - Direct evidence for the effect of lattice distortions in the transport properties of perovskite-type manganite films. PMID- 9984739 TI - Two- and three-dimensional magnetic correlations of Tb in Pb2Sr2TbCu3O8. PMID- 9984740 TI - Vortex dynamics in superfluids: Cyclotron-type motion. PMID- 9984741 TI - Microscopic approach to the response of 3He-4He mixtures. PMID- 9984742 TI - Theory of magnon-hole interaction for the anisotropic t-J model. PMID- 9984743 TI - Superconductivity from doping a spin-liquid insulator: A simple one-dimensional example. PMID- 9984744 TI - Pressure dependence of out-of-plane conduction in La2-xSrxCuO4. PMID- 9984745 TI - Subharmonic structures in Josephson tunneling. PMID- 9984746 TI - Charge transport and Zener tunneling in small Josephson junctions with dissipation. PMID- 9984747 TI - Quantum phase transitions in two dimensions: Experiments in Josephson-junction arrays. PMID- 9984748 TI - Current carried by bound states of a superconducting vortex. PMID- 9984749 TI - Superconductivity up to 8.9 K in two-layer RNi1-xCuxBC (R = Y, Lu). PMID- 9984751 TI - String model of the Cooper pair in the anisotropic superconductor. PMID- 9984750 TI - Current-phase relation in an intermediately coupled superconductor-superconductor junction. PMID- 9984752 TI - Quasiparticle dispersion of the insulating copper oxide Sr2CuO2Cl2 by employing vertical and horizontal double hoppings. PMID- 9984753 TI - Magnetic excitation and superconductivity in overdoped TlSr2CaCu2O7- delta : A 63Cu NMR study. PMID- 9984754 TI - Anomalous thermoelectric power of Ag-containing (Bi,Pb)4Sr3Ca3Cu4Ox-type superconductors prepared by a glass-ceramic method. PMID- 9984755 TI - Anisotropy of the quasiparticle damping in the high-Tc superconductors Bi2Sr2CaCu2O8 and YBa2Cu3O6.9 as seen from angle-resolved photoemission experiments. PMID- 9984756 TI - Hall effect in the mixed state of Y1-xPrxBa2Cu3O7- delta detwinned single crystals. PMID- 9984757 TI - Quasiparticles in the spin-fermion model for CuO2 planes. PMID- 9984758 TI - Pressure dependence of the superconducting critical temperature of Tl2Ba2Ca2Cu3O10+y and Tl2Ba2Ca3Cu4O12+y up to 21 GPa. PMID- 9984760 TI - Dipolon-plasmon interaction in high-Tc superconducting materials. PMID- 9984759 TI - Gd3+ ESR determination of the local spin susceptibility in Gd:YBa2Cu3Oy high temperature superconductors. PMID- 9984761 TI - Thermoelectric power of Y1-xCaxBa2Cu3O7- delta : Contributions from CuO2 planes and CuO chains. PMID- 9984762 TI - Dimensionality and pinning of magnetic vortices in the c-axis aligned Bi2Sr2CaCu2O8+ delta and (Bi,Pb)2Sr2Ca2Cu3O10/Ag tapes irradiated by 5.8-GeV Pb ions. PMID- 9984763 TI - Comment on "Mechanism of the electric-field effect in the high-Tc cuprates" PMID- 9984764 TI - Reply to "Comment on 'Mechanism of the electric-field effect in the high-Tc cuprates' " PMID- 9984765 TI - Lattice distortion of NiO under high pressure. PMID- 9984766 TI - Crack bifurcations in a strained lattice. PMID- 9984767 TI - Insulator-metal transition of fluid molecular hydrogen. PMID- 9984769 TI - Temperature dependence of nuclear inelastic absorption of synchrotron radiation in alpha -57Fe. PMID- 9984768 TI - Infrared response of ordered polarons in layered perovskites. PMID- 9984770 TI - Theory of the density fluctuation spectrum of strongly correlated electrons. PMID- 9984771 TI - Thermopower and nature of the hole-doped states in LaMnO3 and related systems showing giant magnetoresistance. PMID- 9984772 TI - Correlation functions in the three-chain Hubbard ladder. PMID- 9984774 TI - Weak versus strong universality in the two-dimensional random-bond Ising ferromagnet. PMID- 9984773 TI - Numerical evidence for multiplicative logarithmic corrections from marginal operators. PMID- 9984775 TI - Specific-heat anomaly in the Ising antiferromagnet FeBr2 in external magnetic fields. PMID- 9984776 TI - Magnetic excitation spectrum of dimerized antiferromagnetic chains. PMID- 9984777 TI - Long-range magnetic ordering in the spin ladder compound LaCuO2.5 probed by muon spin relaxation. PMID- 9984778 TI - 63Cu nuclear relaxation in the spin-Peierls compound CuGeO3. PMID- 9984779 TI - Frustration-induced Raman scattering in CuGeO3. PMID- 9984781 TI - Impurity in a Luttinger liquid: A numerical study of the finite-size energy spectrum and of the orthogonality catastrophe exponent. PMID- 9984780 TI - Magnetic coupling in thermal-boundary resistance between thin silver films and liquid 3He in the millikelvin regime. PMID- 9984782 TI - Rehybridization and pairing in the cuprates. PMID- 9984783 TI - Lower critical fields of alkali-metal-doped fullerene superconductors. PMID- 9984784 TI - Current-voltage scaling of a Josephson-junction array at irrational frustration. PMID- 9984785 TI - Resistive quantum oscillations in superconducting aluminum microstructures. PMID- 9984786 TI - Pressure dependence of the electronic density of states and Tc in superconducting Rb3C60. PMID- 9984787 TI - CeRu2: A magnetic superconductor with extremely small magnetic moments. PMID- 9984788 TI - Pinning and the mixed-state thermomagnetic transport properties of YBa2Cu3O7- delta. PMID- 9984790 TI - Angle-resolved photoemission spectroscopy study of the superconducting gap anisotropy in Bi2Sr2CaCu2O8+x. PMID- 9984791 TI - Superconducting fluctuations and 63Cu NQR-NMR relaxation in YBa2Cu3O7- delta : Effect of magnetic field and a test for the pairing-state symmetry. PMID- 9984789 TI - Absence of a Kosterlitz-Thouless transition in ultrathin YBa2Cu3O7- delta films. PMID- 9984793 TI - Wide and asymmetric oxygen bond-stretching phonons in La1.85Sr0.15CuO4. PMID- 9984794 TI - Influence of magnetic ordering on the NiO valence band. PMID- 9984792 TI - Linear normal conductance in copper oxide tunnel junctions. PMID- 9984796 TI - Effect of zero-point corrections and k-point sampling on the structural stability determinations of alkali metals. PMID- 9984795 TI - Wave propagation in nonlinear multilayer structures. PMID- 9984797 TI - Detailed band structure for 3C-, 2H-, 4H-, 6H-SiC, and Si around the fundamental band gap. PMID- 9984798 TI - One-particle interchain hopping in coupled Hubbard chains. PMID- 9984799 TI - Calculations of the one-body electronic structure of the strongly correlated systems including self-energy effects. PMID- 9984800 TI - Geometrical non-Abelian bosonization approach for the two-dimensional Hubbard model. PMID- 9984801 TI - Optical activity of small-pitch helical-shaped dielectric media. PMID- 9984802 TI - Importance of a finite speed of heat propagation in metals irradiated by femtosecond laser pulses. PMID- 9984804 TI - Band-tail states and the localized-to-extended transition in amorphous diamond. PMID- 9984803 TI - Photonic band structures of a two-dimensional ionic dielectric medium. PMID- 9984805 TI - Microscopic identification of the compensation mechanisms in Si-doped GaAs. PMID- 9984807 TI - Photoabsorption spectroscopy on isolated GaNAsM clusters. PMID- 9984806 TI - Nonlinear picosecond excitation-correlation luminescence due to free electron hole pairs in GaAs. PMID- 9984808 TI - Intrarow diffusion of Au atoms in the Si(111)-(5 x 2)Au structure. PMID- 9984809 TI - Characterization of carbon-carbon bonds on the SiC(001)c(2 x 2) surface. PMID- 9984810 TI - Atomic structure of monatomic SB steps on clean Si(001) and Ni-contaminated Si(001). PMID- 9984811 TI - Binding energies and envelope functions of light-hole excitons in GaAs/InxGa1 xAs/GaAs strained quantum wells. PMID- 9984813 TI - Charged and neutral exciton phase formation in the magnetically quantized two dimensional electron gas. PMID- 9984812 TI - Interwell excitons in GaAs superlattices. PMID- 9984815 TI - Frequency dependences in transport through a Tomonaga-Luttinger liquid wire. PMID- 9984814 TI - Effect of electron-electron interactions on the average polarizability of a mesoscopic system. PMID- 9984816 TI - Quantum-constriction rectifier. PMID- 9984818 TI - Coulomb blockade of activated conduction. PMID- 9984817 TI - Radiative decay of collective excitations in an array of quantum dots. PMID- 9984819 TI - Persistent current in a one-dimensional ring of fractionally charged quasiparticles. PMID- 9984820 TI - Potential barriers in quantum Hall devices. PMID- 9984821 TI - Multifractality of the quantum Hall wave functions in higher Landau levels. PMID- 9984822 TI - Theory of ballistic-electron-emission microscopy of buried semiconductor heterostructures. PMID- 9984823 TI - Geometry and lattice formation of surface layers of Sn growing on InSb{111}A,B. PMID- 9984824 TI - Vibrational analysis of Nin clusters. PMID- 9984825 TI - Submonolayer scaling due to coalescence of subnanometric copper clusters on alumina. PMID- 9984826 TI - STM evidence of room-temperature charge instabilities in NbSe3. PMID- 9984828 TI - Dynamics of surface profile evolution through surface diffusion. PMID- 9984827 TI - Adsorbate site determination with the scanning tunneling microscope: C2H4 on Cu{110} PMID- 9984829 TI - Prediction of matrix-precipitate interfacial free energies: Application to Al Al3Li. PMID- 9984831 TI - Surface conductivity for Au or Ag on Si(111). PMID- 9984830 TI - Energy-resolved He-atom-scattering study of Ag(110) up to 900 K. PMID- 9984832 TI - Soft-x-ray emission study of Fe/V (001) superlattices. PMID- 9984833 TI - Classical singularities in chaotic atom-surface scattering. PMID- 9984834 TI - Evidence of charge transfer from Na adatoms to the Cs substrate: A collisionally excited autoionization electron-emission study. PMID- 9984835 TI - Core hole screening in chemisorption systems: Role of metal-adsorbate pi --> pi * charge transfer. PMID- 9984837 TI - Electronic and optical properties of red HgI2. PMID- 9984836 TI - Hund's-rule effects in the f 1-f 2 Anderson impurity model: Renormalization of Hund's-rule Coulomb interactions down to low energies. PMID- 9984838 TI - Theory of the optical conductivity of (TMTSF)2PF6 in the midinfrared range. PMID- 9984840 TI - Conductivity in a symmetry-broken phase: Spinless fermions with 1/d corrections. PMID- 9984839 TI - Conformation and electronic structure of polyethylene: A density-functional approach. PMID- 9984841 TI - First-principles theoretical study of metallic states of DCNQI-(Cu,Ag,Li) systems. PMID- 9984842 TI - Self-consistent strong-coupling-perturbation theory for the Anderson model based on Wick's theorem. PMID- 9984843 TI - Electrical transport properties of semimetallic GdX single crystals (X=P, As, Sb, and Bi). PMID- 9984844 TI - Conduction-electron spin relaxation and diffusion in the radical cation salt diperylene hexafluorophosphate. PMID- 9984845 TI - Resonant electron-phonon coupling: Magnetopolarons in InP. PMID- 9984846 TI - Neutral manganese acceptor in GaP: An electron-paramagnetic-resonance study. PMID- 9984848 TI - Photoinduced absorption and photoinduced reflectance in conducting polymer/methanofullerene films: Nonlinear-optical changes in the complex index of refraction. PMID- 9984847 TI - Nature of optical transitions in the charge-transfer region of ZnS:Co and ZnSe:Co. PMID- 9984849 TI - Infrared-ellipsometry evidence of disorder-induced vibrational frequency shifts in hydrogenated-amorphous-silicon thin films. PMID- 9984850 TI - Fourier-transform photoluminescence spectroscopy of excitons bound to group-III acceptors in silicon: Zeeman effect. PMID- 9984851 TI - Epitaxial growth of Si1-yCy alloys characterized as self-organized, ordered, nanometer-sized C-rich aggregates in monocrystalline Si. PMID- 9984852 TI - Magnetothermoelectric properties of the degenerate semiconductor HgSe:Fe. PMID- 9984853 TI - Finite-size effects in one-dimensional strained semiconductor heterostructures. PMID- 9984854 TI - Band dispersions of the pi -bonded-chain reconstruction of Si(111)3 x 1-Li: A critical evaluation of theory and experiment. PMID- 9984855 TI - Mode locking in quantum-Hall-effect point contacts. PMID- 9984856 TI - Weak localization in back-gated Si/Si0.7Ge0.3 quantum-well wires fabricated by reactive ion etching. PMID- 9984857 TI - Exciton and trion spectral line shape in the presence of an electron gas in GaAs/AlAs quantum wells. PMID- 9984858 TI - Tunneling between parallel two-dimensional electron gases. PMID- 9984859 TI - Dissipative chaos in semiconductor superlattices. PMID- 9984861 TI - Effect of strain on a second-order van Hove singularity in AlxGa1-xAs/InyGa1-yAs quantum wells. PMID- 9984860 TI - Self-consistent calculations and magnetoluminescence studies of strained InP/InxGa1-xAs heterojunctions. PMID- 9984863 TI - Longitudinal magnetoresistance of superlattices caused by barrier inhomogeneity. PMID- 9984862 TI - Semiclassical scattering in a circular semiconductor microstructure. PMID- 9984864 TI - Integer quantum Hall effect in double-layer systems. PMID- 9984865 TI - Electrical properties of undoped GaxIn1-xP/GaAs quantum wells. PMID- 9984866 TI - Surface acoustic-wave attenuation by a two-dimensional electron gas in a strong magnetic field. PMID- 9984867 TI - Multiple edges of a quantum Hall system in a strong electric field. PMID- 9984869 TI - Reflectance anisotropy of GaAs(100): Dislocation-induced piezo-optic effects. PMID- 9984868 TI - Classical analysis of a network model of quantum Hall systems. PMID- 9984870 TI - Theory of charge-density and spin-density excitations for two electrons in a circular quantum dot. PMID- 9984871 TI - Probing optical-phonon propagation in GaAs/AlxGa1-xAs quantum-well samples via their nonequilibrium population. PMID- 9984873 TI - Electromagnetic properties of a dielectric grating. II. Quantum wells excited by surface waves. PMID- 9984872 TI - Electromagnetic properties of a dielectric grating. I. Propagating, evanescent, and guided waves. PMID- 9984874 TI - Effect of the spin split-off band on optical absorption in p-type Ga1-xInxAsyP1-y quantum-well infrared detectors. PMID- 9984875 TI - Electronic properties of the leaky quantum-well system Ag(111)/Au/Ag. PMID- 9984876 TI - Quantum transport theory for the ac response of interacting resonant-tunneling devices. PMID- 9984878 TI - Electron states and microstructure of thin a-C:H layers. PMID- 9984877 TI - Microstructure of CuAu-I-type ordered phase in III-V semiconductor alloys grown on a (001) substrate. PMID- 9984879 TI - Properties of two-dimensional Coulomb clusters confined in a ring. PMID- 9984881 TI - Fractal conductance fluctuations in generic chaotic cavities. PMID- 9984880 TI - Theory of time-resolved light emission from polaritons in a semiconductor microcavity under resonant excitation. PMID- 9984882 TI - Nonequilibrium dc noise in a Luttinger liquid with an impurity. PMID- 9984883 TI - Ultrathin epitaxial iron films on a highly asymmetrical substrate: Fe/Cu(311). PMID- 9984884 TI - Spatial structure determination of ( sqrt 3 x sqrt 3)R30 degrees and (1.5 x 1.5)R18 degrees CO or Cu(111) using angle-resolved photoemission extended fine structure. PMID- 9984886 TI - Evolution of surface morphology during growth and ion erosion of thin films. PMID- 9984885 TI - Influence of multiatom interactions on the shapes and energetics of two dimensional homoepitaxial clusters on close-packed metallic surfaces. PMID- 9984887 TI - Influence of growth conditions on subsequent submonolayer oxide decomposition on Si(111). PMID- 9984888 TI - Local magnetic properties and electronic structures of 3d and 4d impurities in Cu clusters. PMID- 9984889 TI - Surface resistivity induced by isolated atoms and atomic clusters on metallic surfaces. PMID- 9984890 TI - Coverage-dependent frequency for Li-atom vibrations on Cu(111). PMID- 9984891 TI - Characterization of self-limiting SiH2Cl2 chemisorption and photon-stimulated desorption as elementary steps for Si atomic-layer epitaxy. PMID- 9984892 TI - Mean escape depth of signal photoelectrons from amorphous and polycrystalline solids. PMID- 9984893 TI - Hindered and modulated rotational states and spectra of adsorbed diatomic molecules. PMID- 9984894 TI - Thermodynamical study of the interaction between clusters. PMID- 9984895 TI - Charge transfer for slow H atoms interacting with Al: Atomic levels and linewidths. PMID- 9984896 TI - Excitons in solid C60. PMID- 9984897 TI - Comment on "Many-body analysis of the effects of electron density and temperature on the intersubband transition in GaAs/AlxGa1-xAs multiple quantum wells" PMID- 9984899 TI - Erratum: Environment-dependent tight-binding potential model PMID- 9984898 TI - Reply to "Comment on 'Many-body analysis of the effects of electron density and temperature on the intersubband transition in GaAs/AlxGa1-xAs multiple quantum wells"' PMID- 9984900 TI - Polarization dependence of Born effective charge and dielectric constant in KNbO3. PMID- 9984901 TI - Efficient iterative schemes for ab initio total-energy calculations using a plane wave basis set. PMID- 9984902 TI - Self-consistent relativistic full-potential Korringa-Kohn-Rostoker total-energy method and applications. PMID- 9984904 TI - Spin- and charge-rotation invariant approach to the Hubbard model. PMID- 9984903 TI - Estimates of electronic interaction parameters for LaMO3 compounds (M=Ti-Ni) from ab initio approaches. PMID- 9984906 TI - Phase-conjugated signal induced and enhanced by weak localization of excitonic polaritons. PMID- 9984905 TI - Differences between random-potential and random-magnetic-field localization in quasi-one-dimensional systems. PMID- 9984907 TI - ac-conductivity measurements on La2NiO4+ delta. PMID- 9984909 TI - Large omnidirectional band gaps in metallodielectric photonic crystals. PMID- 9984908 TI - Electrons, pseudoparticles, and quasiparticles in the one-dimensional many electron problem. PMID- 9984910 TI - Electron scattering by a cut-off atomic potential: Application to electron properties in atomic liquids. PMID- 9984911 TI - Electronic phase transitions in the spin-1/2 Falicov-Kimball model. PMID- 9984912 TI - Properties of the layered BaCo1-xNixS2 alloy system. PMID- 9984914 TI - Shallow electron centers in silver halides. PMID- 9984913 TI - Ab initio optical conductivity in LaMO3 (M=Ti-Cu). PMID- 9984915 TI - Nature of the bulk defects in GaAs through high-temperature quenching studies. PMID- 9984916 TI - Single-site approximation for the s-f model in ferromagnetic semiconductors. PMID- 9984917 TI - Isotopic effects on the lattice constant in compound semiconductors by perturbation theory: An ab initio calculation. PMID- 9984918 TI - Ultrafast kinetics of evolution of optical phonons in a photoinjected highly excited plasma in semiconductors. PMID- 9984919 TI - Hall factor in strained p-type doped Si1-xGex alloy. PMID- 9984920 TI - Al-H and Al-D complexes in Si: A uniaxial-stress study of the hydrogen vibrational modes. PMID- 9984921 TI - Origin of buckling-dimer-row formation of Si(001) surfaces. PMID- 9984923 TI - Carrier relaxation and electronic structure in InAs self-assembled quantum dots. PMID- 9984922 TI - Evidence for three surface components in the 3d core-level photoemission spectra of Ge(100)-(2 x 1) surface. PMID- 9984924 TI - Self-consistent density of states for a single- and double-quantum-well structure in a parallel magnetic field. PMID- 9984925 TI - Magneto-optical experiments on GaAs/InxGa1-xAs/AlyGa1-yAs modulation-doped single quantum wells. PMID- 9984926 TI - Nature of one-dimensional excitons in polysilanes. PMID- 9984927 TI - Quasi-two-dimensional electron-hole plasma in a quantum well: Hartree, exchange, and correlation energies. PMID- 9984928 TI - Systematics of properties of the electron gas in deep-etched quantum wires. PMID- 9984929 TI - Magnetoexcitons and correlated electrons in quantum dots in a magnetic field. PMID- 9984930 TI - Classical chaos and ballistic transport in a mesoscopic channel. PMID- 9984931 TI - Pseudopotential-based multiband k PMID- 9984932 TI - Dynamical response of double parabolically graded quantum wells. PMID- 9984934 TI - Effects of nonlocal response and level quantization on electronic excitations of a bimetallic jellium film in an AlxGa1-xAs heterostructure. PMID- 9984933 TI - Plasmon dispersion in strongly correlated superlattices. PMID- 9984935 TI - Conductance fluctuations in a double-barrier resonant-tunneling structure with three-dimensional electrodes. PMID- 9984936 TI - Signal propagation in electron waveguides: Transmission-line analogies. PMID- 9984937 TI - First-order resonant Raman scattering under an electric field. PMID- 9984938 TI - Phonons in semiconductor planar microcavities: A Raman scattering study. PMID- 9984939 TI - Theory of Raman spectra of heavily doped semiconductor multiple quantum wells. PMID- 9984940 TI - Carrier relaxation and thermal activation of localized excitons in self-organized InAs multilayers grown on GaAs substrates. PMID- 9984941 TI - Rapid carrier relaxation in self-assembled InxGa1-xAs/GaAs quantum dots. PMID- 9984942 TI - Numerically stable Hermitian secular equation for the envelope-function approximation for superlattices. PMID- 9984944 TI - Fabrication and physical properties of radio frequency sputtered Cd1-xMnxS thin films. PMID- 9984943 TI - State filling and time-resolved photoluminescence of excited states in InxGa1 xAs/GaAs self-assembled quantum dots. PMID- 9984945 TI - Quasiparticle lifetime in a two-dimensional electron system in the limit of low temperature and excitation energy. PMID- 9984947 TI - Polarized interacting exciton gas in quantum wells and bulk semiconductors. PMID- 9984946 TI - Effective-mass theory for InAs/GaAs strained coupled quantum dots. PMID- 9984948 TI - Numerical calculation of the optical absorption in semiconductor quantum structures. PMID- 9984949 TI - Conductance fluctuations near the ballistic-transport regime. PMID- 9984950 TI - Origin of conductance fluctuations in large circular quantum dots. PMID- 9984951 TI - Single-impurity Anderson model out of equilibrium. PMID- 9984952 TI - Numerical confirmation of universality of transmission microsymmetry relations in a four-probe quantum dot. PMID- 9984953 TI - Transport properties of ion-implanted and chemically doped polyaniline films. PMID- 9984954 TI - Spontaneous interlayer coherence in double-layer quantum Hall systems: Symmetry breaking interactions, in-plane fields, and phase solitons. PMID- 9984956 TI - Ultrafast ellipsometry of coherent processes and exciton-exciton interactions in quantum wells at negative delays. PMID- 9984955 TI - Mossbauer study of the magnetic character and ordering process of the cubic gamma -FeSi2 phase obtained by Fe implantation into a Si(100) matrix. PMID- 9984957 TI - Monte Carlo simulation of nonspecular x-ray scattering profiles from multilayers. PMID- 9984958 TI - Scaling behavior in submonolayer film growth: A one-dimensional model. PMID- 9984959 TI - Crystal growth and characterization of Cu-intercalated misfit-layer compounds. PMID- 9984960 TI - Amorphization in the vicinity of a grain boundary: A molecular-dynamics approach. PMID- 9984961 TI - Observation of a superlattice in silver-intercalated NbSe2 by scanning tunneling microscopy. PMID- 9984962 TI - Morphological stability of alloy thin films. PMID- 9984963 TI - Final-state magnetic dichroism in Fe 3s photoemission. PMID- 9984964 TI - Low-energy electron microscopy study of step mobilities on Si(001). PMID- 9984966 TI - Brownian motion and shape fluctuations of single-layer adatom and vacancy clusters on surfaces: Theory and simulations. PMID- 9984965 TI - Ostwald ripening of two-dimensional islands on Si(001). PMID- 9984967 TI - Evidence for a strain-stabilized bct phase of cobalt deposited on Pd{100}: An x ray photoelectron diffraction study. PMID- 9984968 TI - Atomic and electronic structure of ideal and reconstructed alpha -Sn (111) surface. PMID- 9984969 TI - Electronic effects in scanning tunneling microscopy of graphite: A Green's function calculation based on the tight-binding model. PMID- 9984971 TI - Structural and vibrational analysis of amorphous Au55 clusters. PMID- 9984970 TI - Electronic structure of silver and copper ultrathin films on V(100): Quantum-well states. PMID- 9984972 TI - A dynamically and kinetically consistent mechanism for H2 adsorption/desorption from Si(100)-2 x 1. PMID- 9984974 TI - Direct calculation of the two-photon line strength of a Gamma 1g- Gamma 1g transition in octahedral symmetry. PMID- 9984973 TI - Experimental and theoretical studies of the electronic structure of TiS2. PMID- 9984975 TI - Competition between the Mott transition and Anderson localization in one dimensional disordered interacting electron systems. PMID- 9984976 TI - Bandwidth dependence of insulator-metal transitions in perovskite cobalt oxides. PMID- 9984977 TI - Mott transition in degenerate Hubbard models: Application to doped fullerenes. PMID- 9984978 TI - Optical absorption of CuGeO3. PMID- 9984980 TI - Titanium-hydrogen defects in silicon. PMID- 9984979 TI - Optical conductivity of strongly correlated electron systems. PMID- 9984982 TI - Nondiffusive excitonic transport in GaAs and the effects of momentum scattering. PMID- 9984983 TI - Observation of compensating Ga vacancies in highly Si-doped GaAs. PMID- 9984981 TI - Optical detection of electron nuclear double resonance on a residual donor in wurtzite GaN. PMID- 9984985 TI - Step dynamics and equilibrium structure of monoatomic steps on Si(100)-2 x 1. PMID- 9984984 TI - Reconstruction transitions during molecular-beam epitaxy on GaAs(111)B vicinal surfaces studied by scanning electron microscopy. PMID- 9984986 TI - Structure and properties of clean and In-covered Ge(103) surfaces. PMID- 9984987 TI - Surface unwetting during growth of Ag on Si(001). PMID- 9984988 TI - Topological characterization of delocalization in a spin-orbit coupling system. PMID- 9984989 TI - Zero-dimensional excitons in (Zn,Cd)Se quantum structures. PMID- 9984990 TI - Quantum wells with zero valence-band offset: Drastic enhancement of forbidden excitonic transitions. PMID- 9984992 TI - Observation of a D- triplet transition in GaAs/AlxGa1-xAs multiple quantum wells. PMID- 9984991 TI - Evolution of the interband absorption threshold with the density of a two dimensional electron gas. PMID- 9984993 TI - Frequency-dependent admittance of a two-dimensional quantum wire. PMID- 9984994 TI - Thermopower of quantum nanowires in a magnetic field. PMID- 9984995 TI - Folded and confined one-dimensional plasmons in modulated wires. PMID- 9984996 TI - Pressure and alloy-composition dependence of Al/Ga1-xAlxAs (100) Schottky barriers. PMID- 9984998 TI - Nonlinear sigma model for partially polarized quantum Hall states. PMID- 9984997 TI - Tunneling spectroscopy of hole plasmons in a valence-band quantum well. PMID- 9984999 TI - Composite fermions with orbital magnetization. PMID- 9985001 TI - Effects of contact metals on electroluminescence from embedded nanosize-Si particle films. PMID- 9985000 TI - p- and n-type cubic GaN epilayers on GaAs. PMID- 9985002 TI - Optical transitions in beta -FeSi2 films. PMID- 9985003 TI - Thermally induced interface degradation in (111) Si/SiO2 traced by electron spin resonance. PMID- 9985005 TI - Monte Carlo determination of heteroepitaxial misfit structures. PMID- 9985004 TI - Grain boundary and surface energies of fcc metals. PMID- 9985006 TI - pi -bonded-trimer formation on the clean diamond C(111) surface. PMID- 9985007 TI - Structure and contrast in scanning tunneling microscopy of oxides: FeO monolayer on Pt(111). PMID- 9985009 TI - Magnetically split sp-derived states in fcc-like Fe/Cu(001). PMID- 9985008 TI - Mechanically stretched carbon nanotubes: Induction of chiral current. PMID- 9985011 TI - Random nucleation and growth kinetics. PMID- 9985010 TI - Magnetism of thin Fe films on Cu(100). PMID- 9985012 TI - Single C-C bond in (C60)22- PMID- 9985013 TI - Use of atomic-force microscopy and of a parallel irradiation geometry for in depth characterization of damage produced by swift Kr ions in silicon. PMID- 9985014 TI - Calculation of elastic constants in defected and amorphous silicon by quantum simulations. PMID- 9985015 TI - Ground-state properties and high-pressure phase of beryllium chalcogenides BeSe, BeTe, and BeS. PMID- 9985017 TI - X-ray study of the ferroelastic incommensurate phase of LiKSO4 under uniaxial pressure. PMID- 9985016 TI - Phase selection and transformation kinetics in KC60. PMID- 9985018 TI - Localization of light for dissipative and disordered one-dimensional systems. PMID- 9985019 TI - Unpredicted density dependence of hydrogen bonding in water found by neutron diffraction. PMID- 9985020 TI - Properties of gallium in porous glass. PMID- 9985021 TI - Coupled optical interface modes in a Fibonacci dielectric superlattice. PMID- 9985022 TI - Localization of light: Dual symmetry between absorption and amplification. PMID- 9985023 TI - Method to measure the localization length in one dimension. PMID- 9985024 TI - Effect of tunneling disorder on the low-temperature heat capacities of 3He and 4He in zeolite channels. PMID- 9985025 TI - Site correlation, anomalous diffusion, and enhancement of the localization length. PMID- 9985026 TI - Spin-wave hybridization and magnetic anisotropies in a thick bcc cobalt film. PMID- 9985028 TI - Effects of intrinsic spin on electronic transport through magnetic barriers. PMID- 9985027 TI - Magnetic properties of M13 clusters (M=Y, Zr, Nb, Mo, and Tc). PMID- 9985029 TI - High-temperature thermopower in La2/3Ca1/3MnO3 films: Evidence for polaronic transport. PMID- 9985030 TI - Vibrational mode of solitons in two-dimensional easy-plane antiferromagnets. PMID- 9985031 TI - Nonmagnetic impurities in two- and three-dimensional Heisenberg antiferromagnets. PMID- 9985033 TI - Exact results for resonating-valence-bond states on two-dimensional (narrow) systems. PMID- 9985032 TI - Exchange integrals of vanadates as revealed by magnetic-susceptibility measurements of NaV2O5. PMID- 9985034 TI - Type-II antiferromagnetism in compounds of iron with 4d metals. PMID- 9985036 TI - Inelastic-neutron-scattering studies of spin-wave excitations in the pnictides MnSb and CrSb. PMID- 9985035 TI - Behavior of magnetic impurities in gapless Fermi systems. PMID- 9985037 TI - Calculation of the out-of-plane dynamical correlation for CsNiF3. PMID- 9985039 TI - Rigorous results for the one-dimensional symmetric Anderson model. PMID- 9985038 TI - Correlation of the size effect with the thermoelectric power for the Pr-based manganites Pr0.7Ca0.3-xSrxMnO3. PMID- 9985041 TI - Oscillatory switching under a rapidly varying magnetic field. PMID- 9985040 TI - 1/N expansion for critical exponents of magnetic phase transitions in the CPN-1 model for 2H2O on Pt(111) with second-harmonic generation. PMID- 9985325 TI - Charge transfer and surface scattering at Cu-C60 planar interfaces. PMID- 9985328 TI - Critical temperature for mound formation in molecular-beam epitaxy. PMID- 9985327 TI - Structure of the alpha -Cr2O3 (0001) surface: An ab initio total-energy study. PMID- 9985329 TI - Molecular-dynamics simulations of the dynamical excitations in commensurate submonolayer films of nitrogen molecules on graphite. PMID- 9985331 TI - Indium adsorption on the Au(111) surface at room temperature. PMID- 9985330 TI - Medium-energy ion-scattering study of the temperature dependence of the structure of Cu(111). PMID- 9985333 TI - Surface electronic structure of clean and hydrogen-chemisorbed SixGe1-x alloy surfaces. PMID- 9985332 TI - Solubility isotherms of hydrogen in epitaxial Nb(110) films. PMID- 9985334 TI - First-principles calculation of oxygen adsorption on Zr(0001) surface: Possible site occupation between the second and the third layer. PMID- 9985336 TI - Lifetime of surface plasmons of simple metals: Volume versus surface contributions. PMID- 9985335 TI - Magnetic dimers of transition-metal atoms on the Ag(001) surface. PMID- 9985337 TI - Two-dimensional adatom gas on the Si(111)-( sqrt 3 x sqrt 3)-Ag surface detected through changes in electrical conduction. PMID- 9985338 TI - Raman study of the polymerized state of RbC60 and CsC60. PMID- 9985340 TI - Hydrogen diffusion on Si(001). PMID- 9985339 TI - Location of ion-induced surface Auger decay processes from scattered-ion measurements. PMID- 9985341 TI - Pseudopotential effects in alkali clusters by the pseudo-Hamiltonian technique. PMID- 9985342 TI - Theoretical studies of spin-polarized LEED rotation curves: Clean W(100) and Fe overlayers on W(100). PMID- 9985343 TI - Role of hydrogen in the initial stage of diamond heteroepitaxy on silicon. PMID- 9985344 TI - Erratum: Unified treatment of temperature, concentration, and electric-field dependences of variable-range-hopping conductivity PMID- 9985345 TI - Tight-binding calculation of formation energies in multicomponent oxides: Application to the MgO-CaO phase diagram. PMID- 9985346 TI - Inelastic neutron scattering from single crystal Zn under high pressure. PMID- 9985347 TI - Comparative investigation of elastic diffuse scattering in C60 powders. PMID- 9985348 TI - Free-energy calculations of thermodynamic, vibrational, elastic, and structural properties of alpha -quartz at variable pressures and temperatures. PMID- 9985349 TI - Validity of Avrami's kinetics for random and nonrandom distributions of germs. PMID- 9985351 TI - Characterization of radiation-induced lattice vacancies in intermetallic compounds by means of positron-lifetime studies. PMID- 9985350 TI - Monte Carlo stochastic-dynamics study of dielectric response and nonergodicity in proton glass. PMID- 9985352 TI - Diffusion of iron and nickel in single-crystalline copper. PMID- 9985354 TI - Relaxation of electronic defects in pure and doped La2O3 observed by perturbed angular correlations. PMID- 9985353 TI - Even-parity excitons in condensed xenon. PMID- 9985355 TI - Redistribution of La-Al nearest-neighbor distances in the metallic glass Al0.91La0.09. PMID- 9985356 TI - Transport properties of random media: An energy-density CPA approach. PMID- 9985357 TI - Dynamics in discrete two-dimensional nonlinear Schrodinger equations in the presence of point defects. PMID- 9985358 TI - High-pressure Raman study of the N2 stretching vibration in argon-nitrogen mixtures at room temperature. PMID- 9985359 TI - Raman-scattering study of isotopically engineered crystalline C60. PMID- 9985360 TI - Evidence of a critical time in constrained kinetic Ising models. PMID- 9985361 TI - Collective particle flow through random media. PMID- 9985362 TI - Rotational motion of methyl groups in solids. PMID- 9985363 TI - One-center trapping of the holes in alkali halide crystals. PMID- 9985364 TI - Single-molecule kinetic energy of condensed normal deuterium. PMID- 9985365 TI - Energy relaxation dynamics in the optical excited state of myoglobin. PMID- 9985366 TI - Monte Carlo simulation at very low temperature: The spin stiffness of the two dimensional Heisenberg model. PMID- 9985367 TI - Static and dynamic simulation in the classical two-dimensional anisotropic Heisenberg model. PMID- 9985368 TI - Transfer-matrix Monte Carlo estimates of critical points in the simple-cubic Ising, planar, and Heisenberg models. PMID- 9985369 TI - Quantum spin ladders at T=0 and at high temperatures studied by series expansions. PMID- 9985370 TI - Spin dynamics in magnets: Equation of motion and finite temperature effects. PMID- 9985372 TI - Magnon band structure of periodic composites. PMID- 9985371 TI - Spin configurations in an amorphous random-anisotropy magnet. PMID- 9985373 TI - Growth of stabilized gamma -Fe films and their magnetic properties. PMID- 9985374 TI - Interacting small-particle systems: Modified local-mean-field model. PMID- 9985375 TI - Theory of interaction of light with an intensive spin wave in a ferromagnetic film. PMID- 9985377 TI - Shape anisotropy of magnetic heterostructures. PMID- 9985376 TI - Angular dependence of the perpendicular giant magnetoresistance of multilayers. PMID- 9985378 TI - Magnetoelastic contribution to the interface anisotropy of Pd/Co metallic multilayers. PMID- 9985379 TI - Magnetization studies of Ho/Y superlattices: Role of magnetoelastic coupling effects. PMID- 9985380 TI - Structural analysis of CuGeO3: Relation between nuclear structure and magnetic interaction. PMID- 9985381 TI - Theoretical studies of the temperature dependence of zero-field splitting of Cr3+ centers in ruby. PMID- 9985382 TI - ESR of Gd3+ in magnetically ordered Eu2CuO4. PMID- 9985384 TI - Electron-nuclear double-resonance analysis of diatomic sulfur and selenium defects in NaBr and NaI. PMID- 9985383 TI - d=2 Ising strip with two surface fields solved using the transfer-matrix method. PMID- 9985385 TI - Tetragonal domain structure and magnetoresistance of La1-xSrxCoO3. PMID- 9985386 TI - Orbital and spin magnetic moments of TPt3 (T=V, Cr, Mn, Fe, and Co). PMID- 9985387 TI - Non-Fermi-liquid behavior in the specific heat over two decades of temperature in doped UPt3. PMID- 9985388 TI - Non-Fermi-liquid theory of a compactified Anderson single-impurity model. PMID- 9985390 TI - Transition from magnetic to nonmagnetic ground state in a heavy-fermion compound Ce7Ni3 under high pressure. PMID- 9985389 TI - Spontaneous behavior and magnetic field and pressure effects on La2/3Ca1/3MnO3 perovskite. PMID- 9985391 TI - Magnetic and transport properties of epitaxial Fe/V(001) superlattice films. PMID- 9985392 TI - Vortex line in superfluid 4He: A variational Monte Carlo calculation. PMID- 9985393 TI - Nonlinear pattern dynamics in Josephson-junction arrays. PMID- 9985394 TI - One-dimensional Josephson arrays as superlattices for single Cooper pairs. PMID- 9985395 TI - Charge solitons in one-dimensional arrays of serially coupled Josephson junctions. PMID- 9985397 TI - Recovery of superconductivity and the critical field in layered superconductors. PMID- 9985396 TI - Resonant macroscopic quantum tunneling in SQUID systems. PMID- 9985398 TI - Imaginary part of the infrared conductivity of a dx2-y2 superconductor. PMID- 9985400 TI - Nonlinear dynamics of vortices in ultraclean type-II superconductors: Integrable wave equations in cylindrical geometry. PMID- 9985399 TI - Spatially resolved observation of the resistive transition in superconducting wire networks. PMID- 9985401 TI - From BCS-like superconductivity to condensation of local pairs: A numerical study of the attractive Hubbard model. PMID- 9985402 TI - Bond-charge interaction in the extended Hubbard chain. PMID- 9985403 TI - Conductivity onset and superconducting properties of quench-condensed gallium films deposited onto different substrates. PMID- 9985404 TI - Pressure-induced phonon softening and electronic topological transition in HgBa2CuO4. PMID- 9985405 TI - First-order melting and dynamics of flux lines in a model for YBa2Cu3O7- delta. PMID- 9985406 TI - Superconducting gap symmetries in YBa2Cu3O7- delta compatible with electronic Raman efficiencies and the local-density-approximation band structure. PMID- 9985407 TI - Magnetic susceptibility and the Landau Fermi-liquid parameter of the Hubbard model and the three-band CuO2 model. PMID- 9985408 TI - Conductivity peak, relaxation dynamics, and superconducting gap of YBa2Cu3O7 studied by terahertz and femtosecond optical spectroscopies. PMID- 9985409 TI - Quantum creep and pinning properties of oxygen-deficient YBa2Cu3Oxn films. PMID- 9985410 TI - Observation of a three-dimensional vortex-line liquid in a highly c-axis-oriented (Bi,Pb)2Sr2Ca2Cu3Ox silver-sheathed tape. PMID- 9985412 TI - Dynamics of a single hole in the two-dimensional t-J model in the presence of a magnetic field and the composite nature of quasiparticles. PMID- 9985411 TI - Single vortex creep in Tl2Ba2CaCu2O8 epitaxial thin films. PMID- 9985413 TI - Positron annihilation in the epitaxial superconducting thin-film GdBa2Cu3O7- delta studied by using a pulsed positron beam. PMID- 9985414 TI - Electronic structure of the 1 x 1 YBa2Cu3O7/PrBa2Cu3O7 superlattice: A local-spin density approximation with on-site Coulomb interaction. PMID- 9985415 TI - Comment on "Fluctuations during freezing and melting at the solid-liquid interface of xenon" PMID- 9985416 TI - Reply to "Comment on 'Fluctuations during freezing and melting at the solid liquid interface of xenon' " PMID- 9985417 TI - High-pressure phase of solid hydrogen sulfide. PMID- 9985418 TI - Simple tiling model and phason kinetics for decagonal Al-Cu-Co. PMID- 9985419 TI - Quantizing charged magnetic domain walls: Strings on a lattice. PMID- 9985420 TI - Quantum fluctuations in the Kondo insulators: Slave-boson approach. PMID- 9985421 TI - Intersite Coulomb interaction and Heisenberg exchange. PMID- 9985422 TI - RCuO2.66 delafossites: A dilute s=1/2 kagome-like lattice. PMID- 9985424 TI - Universal low-temperature properties of quantum and classical ferromagnetic chains. PMID- 9985423 TI - Spin-glass behavior of frustrated two-dimensional Penrose lattice in the classical planar model. PMID- 9985426 TI - Interaction effect in the Kondo energy of the periodic Anderson-Hubbard model. PMID- 9985425 TI - Biperiodic oscillatory coupling as a function of the thickness of an embedded Ni layer in Co/Cu/Co/Ni/Co(100) and selection rules for the periods. PMID- 9985427 TI - Invar effect of SrRuO3: Itinerant electron magnetism of Ru 4d electrons. PMID- 9985429 TI - Superconductivity in electron liquids with and without intermediaries. PMID- 9985428 TI - Magnetic circular x-ray dichroism in transverse geometry: Importance of noncollinear ground state moments. PMID- 9985431 TI - Flux effect in superconducting hybrid Aharonov-Bohm rings. PMID- 9985430 TI - dx2-y2 superconductivity in a model of correlated fermions. PMID- 9985432 TI - Fourfold symmetry in the ab plane of the upper critical field for single-crystal Pb2Sr2Y0.62Ca0.38Cu3O8: Evidence for dx2-y2 pairing in a high-Tc superconductor. PMID- 9985433 TI - Nonlocal effects in the critical state of type-II superconductors. PMID- 9985434 TI - Creep of vortices from columnar defects. PMID- 9985435 TI - Effect of columnar defects on reversible magnetization of superconducting Bi2Sr2Ca2Cu3O10+ delta. PMID- 9985436 TI - Large effect of columnar defects on the thermodynamic properties of Bi2Sr2CaCu2O8 single crystals. PMID- 9985437 TI - Simultaneous resistivity onset and first-order vortex-lattice phase transition in Bi2Sr2CaCu2O8. PMID- 9985438 TI - Tilting of the CuO6 octahedra in La1.83-xEu0.17SrxCuO4 as seen by 151Eu Mossbauer spectroscopy. PMID- 9985439 TI - Molecular-orbital theory of monatomic and diatomic substitutional defects as shallow n-type dopants in diamond. PMID- 9985440 TI - Effect of electron-phonon interaction on a one-dimensional correlated electron system. PMID- 9985441 TI - Dielectric-matrix calculation of the volume-plasmon dispersion relation for silicon. PMID- 9985442 TI - Real-space multigrid-based approach to large-scale electronic structure calculations. PMID- 9985443 TI - Optical properties of solids within the independent-quasiparticle approximation: Dynamical effects. PMID- 9985444 TI - Electron momentum-space densities of Li metal: A high-resolution Compton scattering study. PMID- 9985445 TI - Theoretical and experimental study of the graphite 1s x-ray absorption edges. PMID- 9985446 TI - Electronic structure and x-ray photoelectron spectroscopy of the alpha, beta, and gamma phases of Np. PMID- 9985447 TI - Electronic structure and elastic properties of the Ni3X (X=Mn, Al, Ga, Si, Ge) intermetallics. PMID- 9985449 TI - Temperature dependence of electronic states in the t-J model. PMID- 9985448 TI - Divergence of classical trajectories and weak localization. PMID- 9985451 TI - Evaluation of matrix elements of the 8 x 8 k PMID- 9985450 TI - Magnetic polaron in ferro- and antiferromagnetic semiconductors. PMID- 9985452 TI - Electronic structure of ordered silicon alloys: Direct-gap systems. PMID- 9985453 TI - Femtosecond investigation of the hot-phonon effect in GaAs at room temperature. PMID- 9985454 TI - Photoluminescence study of cadmium-related defects in oxygen-rich silicon. PMID- 9985456 TI - Structure and stability of steps on the GaAs(110) surface. PMID- 9985455 TI - Substrate bias effects on the structural and electronic properties of tetrahedral amorphous carbon. PMID- 9985457 TI - Magnetotransport coefficients in a two-dimensional SiGe hole gas. PMID- 9985458 TI - Interband optical absorption in strained InAs/InxGa1-xSb type-II superlattices. PMID- 9985459 TI - Phase transitions in quantum dots. PMID- 9985460 TI - Magnetophonons in short-period superlattices. PMID- 9985461 TI - Electron dynamics in intentionally disordered semiconductor superlattices. PMID- 9985462 TI - Cotunneling in single-electron devices: Effects of stray capacitances. PMID- 9985463 TI - Dispersion of bulk exciton polaritons in a semiconductor microcavity. PMID- 9985464 TI - Time-domain theory of resonant Rayleigh scattering by quantum wells: Early-time evolution. PMID- 9985466 TI - Luminescence dynamics in type-II GaAs/AlAs superlattices near the type-I to type II crossover. PMID- 9985465 TI - Percolation of carriers through low potential channels in thick AlxGa1-xAs (x<0.35) barriers. PMID- 9985468 TI - Theory of the optical response of a dilute ensemble of semiconducting nanoparticles embedded in a dielectric matrix. PMID- 9985467 TI - Optimization of the confinement energy of quantum-wire states in T-shaped GaAs/AlxGa1-xAs structures. PMID- 9985469 TI - Mode splitting in side emission from vertical-cavity surface-emitting lasers. PMID- 9985471 TI - Luminescence from amorphous silicon nanostructures. PMID- 9985470 TI - Microscopic calculation of valence-band states in semiconductor structures in the presence of a magnetic field. PMID- 9985472 TI - Dielectric properties of the quasi-two-dimensional electron liquid in heterojunctions. PMID- 9985473 TI - Composition and structure of the GaN{0001-bar}-(1 x 1) surface. PMID- 9985474 TI - Instabilities of a persistent-photoconductivity semiconductor associated with heat transfer to a He-II film. PMID- 9985475 TI - Competing desorption pathways during epitaxial growth: LEEM investigation of Cu/W(110) heteroepitaxy. PMID- 9985476 TI - Oscillatory exchange coupling in Fe/Cr multilayers. PMID- 9985477 TI - Real-time x-ray-scattering measurement of the nucleation kinetics of cubic gallium nitride on beta -SiC(001). PMID- 9985479 TI - Excitation of phonons and forward focusing in x-ray photoemission from the valence band. PMID- 9985478 TI - Determination of the atomic geometries of the (110) surfaces of CuCl and CuBr by dynamical low-energy electron diffraction intensity analysis. PMID- 9985480 TI - Structure of polygonal defects in graphitic carbon sheets. PMID- 9985481 TI - Structural stability of adatom islands on fcc(111) transition-metal surfaces. PMID- 9985482 TI - Theory of surface and interface transverse elastic waves in N-layer superlattices. PMID- 9985483 TI - Effects of crystalline microstructure on epitaxial growth. PMID- 9985484 TI - Structural and electrical properties of a metallic rough-thin-film system deposited on liquid substrates. PMID- 9985485 TI - Simple model to calculate surface magnetization from spin-polarized metastable deexcitation spectroscopy: Fe/Ag(100). PMID- 9985486 TI - Charge transfer in hyperthermal energy collisions of Li+ with alkali-metal covered Cu(001). I. Dynamics of charge state formation. PMID- 9985488 TI - Dynamic polarizability of small simple metal clusters in dielectric media. PMID- 9985487 TI - Charge transfer in hyperthermal energy collisions of Li+ with alkali-metal covered Cu(001). II. Dynamics of excited-state formation. PMID- 9985490 TI - Phonon contributions to photohole linewidths observed for surface states on copper. PMID- 9985489 TI - Photoionization of metal clusters. PMID- 9985492 TI - Effects of orbital degeneracy on the Mott transition in infinite dimensions. PMID- 9985491 TI - Wave-function and level statistics of random two-dimensional gauge fields. PMID- 9985493 TI - Hubbard model versus t-J model: The one-particle spectrum. PMID- 9985494 TI - Optical spectroscopy of the charge-ordering transition in La1.67Sr0.33NiO4. PMID- 9985495 TI - Force and conductance jumps in atomic-scale metallic contacts. PMID- 9985496 TI - 4d resonant inelastic x-ray scattering in gadolinium. PMID- 9985498 TI - Orthorhombic symmetry DX centers in S-doped GaSb, GaAs, and AlxGa1-xAs. PMID- 9985497 TI - Pressure-induced distortion of the amorphous tetrahedral network in a-GaSb: Direct evidence from EXAFS. PMID- 9985499 TI - Continuum contribution to excitonic four-wave mixing due to interaction-induced nonlinearities. PMID- 9985501 TI - Spin splitting of subbands in quasi-one-dimensional electron quantum channels. PMID- 9985500 TI - Finite chain-length effect on nonlinear optical response in polysilane as investigated by electroabsorption spectroscopy. PMID- 9985502 TI - Current-induced decoupling of edge states in the integer quantum Hall effect. PMID- 9985503 TI - dc transport in quantum wires. PMID- 9985504 TI - Femtosecond luminescence measurements of the intersubband scattering rate in AlxGa1-xAs/GaAs quantum wells under selective excitation. PMID- 9985505 TI - Probing the band structure of a two-dimensional hole gas using a one-dimensional superlattice. PMID- 9985506 TI - Origin of the surface metallization in single-domain K/Si(100)2 x 1. PMID- 9985508 TI - Inhibition of spontaneous emission from quantum-well magnetoexcitons. PMID- 9985507 TI - Internal electron-electron interactions in one-dimensional systems detected by Raman spectroscopy. PMID- 9985510 TI - Theory of electromagnetic response and collective excitations of a square lattice of antidots. PMID- 9985509 TI - Even-odd correlations in capacitance fluctuations of quantum dots. PMID- 9985511 TI - Reflection symmetric ballistic microstructures: Quantum transport properties. PMID- 9985512 TI - Dephasing of Bloch oscillations in epitaxial superlattices. PMID- 9985513 TI - Distribution of the absorption by chaotic states in quantum dots. PMID- 9985515 TI - Composite fermions in tilted magnetic fields and the effect of the confining potential width on the composite-fermion effective mass. PMID- 9985514 TI - Collective modes and electronic spectral function in smooth edges of quantum hall systems. PMID- 9985516 TI - Diffusion thermopower at even-denominator fractions. PMID- 9985517 TI - Controlling Schottky energy barriers in organic electronic devices using self assembled monolayers. PMID- 9985518 TI - Superradiant emission from Bloch oscillations in semiconductor superlattices. PMID- 9985519 TI - Photoluminescent spectrum and dynamics of Si+-ion-implanted and thermally annealed SiO2 glasses. PMID- 9985520 TI - Evidence for the presence of the multipole plasmon mode on Ag surfaces. PMID- 9985521 TI - Size-related ferroelectric-domain-structure transition in a polycrystalline PbTiO3 thin film. PMID- 9985522 TI - Bonding properties of Li2Ca and Mg2Ca. PMID- 9985523 TI - Orientation and twins separation in a micellar cubic crystal under oscillating shear. PMID- 9985524 TI - Quantum simulation of high-density amorphous ice. PMID- 9985525 TI - Deconvolution of lifetime broadening at rare-earth LIII edges compared to resonant inelastic x-ray scattering measurements. PMID- 9985526 TI - Lattice sums as limit values of model liquid energies. PMID- 9985527 TI - Effective one-dimensionality of universal ac hopping conduction in the extreme disorder limit. PMID- 9985528 TI - Strain-induced shifts of the infrared-active phonon of cubic boron nitride. PMID- 9985529 TI - Line broadening in the collective dynamics of liquid and solid water. PMID- 9985530 TI - Two interacting particles in the Harper model. PMID- 9985532 TI - Dilution of a layered antiferromagnet: Magnetism in MnxZn1-xPS3. PMID- 9985531 TI - Electronic Raman scattering from La0.7Sr0.3MnO3 exhibiting giant magnetoresistance. PMID- 9985533 TI - Optimized mean-field theory for the three-dimensional XY spin model. PMID- 9985534 TI - Error reduction using covariance in quantum Monte Carlo simulations. PMID- 9985535 TI - Single-hole dispersion relation for the real CuO2 plane. PMID- 9985536 TI - Overscreened single-channel Kondo problem. PMID- 9985538 TI - Low-temperature specific heat of La0.67Ba0.33MnO3 and La0.8Ca0.2MnO3. PMID- 9985537 TI - 55Mn nuclear-magnetic-resonance study of the GdMn2 hydrides. PMID- 9985539 TI - Numerical results for the two-dimensional random-bond three-state Potts model. PMID- 9985540 TI - Evidence for low-Fe-moment state and Ru-enhanced antiferromagnetic exchange in glassy Fe90Zr10. PMID- 9985541 TI - X-ray photoemission measurements of La1-xCaxCoO3 (x=0, 0.5). PMID- 9985542 TI - Nuclear resonance small-angle scattering of x rays. PMID- 9985543 TI - Classical spins in van Hove superconductors. PMID- 9985544 TI - Thermally activated flux creep in K3C60 single crystals. PMID- 9985546 TI - Superconductivity in K3Ba3C60. PMID- 9985545 TI - Large copper isotope effect in oxygen depleted YBa2Cu3Oy: Importance of Cu dominated phonon modes in the pairing mechanism. PMID- 9985547 TI - 169Tm Mossbauer-spectroscopy study of the magnetic superconductor TmNi2B2C. PMID- 9985548 TI - Line-shape analyses of magnon Raman spectra of a PrBa2Cu2.7Al0.3O7 single crystal. PMID- 9985549 TI - dx2-y2 symmetry and the pairing mechanism. PMID- 9985550 TI - Specific heat and Knight shift of cuprates within the van Hove scenario. PMID- 9985551 TI - First-order flux-lattice melting of a frustrated XY model with a PMID- 9985552 TI - Site dependence of large oxygen isotope effect in Y0.7Pr0.3Ba2Cu3O6.97. PMID- 9985554 TI - Disorder-induced roughening in the three-dimensional Ising model. PMID- 9985553 TI - Universal Hall mobility in c-axis-oriented Y0.5Ca0.5Ba2Cu3O7- delta thin films. PMID- 9985555 TI - Constant-pressure first-principles studies on the transition states of the graphite-diamond transformation. PMID- 9985557 TI - First-principles calculation of positron annihilation characteristics at metal vacancies. PMID- 9985556 TI - Pretransitional dynamics of the structural phase transition in anthracene-TCNB: A comparison of Raman-scattering and inelastic-neutron-scattering experiments. PMID- 9985558 TI - Total yield and polar-angle distributions of biomolecules sputtered by fast heavy ions. PMID- 9985559 TI - Soft-x-ray emission and the local p-type partial density of electronic states in Y2O3: Experiment and theory. PMID- 9985561 TI - Precursor effects and premartensitic transformation in Ni2MnGa. PMID- 9985560 TI - Statics and dynamics of incommensurate crystal phases. PMID- 9985562 TI - Annihilation of positronium in alpha -SiO2 investigated by combined angular correlation and lifetime measurements. PMID- 9985563 TI - Low-temperature excess specific heat and fragility in semicrystalline polymers. PMID- 9985564 TI - Electron-spin-resonance identification of a -CH2 -dot radical in irradiated amorphous SiO2:OH. PMID- 9985566 TI - Substitutional disorder in a Fibonacci chain: Resonant eigenstates and instability of the spectrum. PMID- 9985565 TI - Time-resolved EPR of spin-polarized mobile H atoms in amorphous silica: The involvement of small polarons. PMID- 9985567 TI - Length scaling of conductance distribution for random fractal lattices. PMID- 9985568 TI - Fracture of disordered three-dimensional spring networks: A computer simulation methodology. PMID- 9985569 TI - Low-lying excitation spectrum of quantum many-body systems. PMID- 9985570 TI - Femtosecond time-resolved spectroscopy of self-trapping processes of holes and electron-hole pairs in alkali bromide crystals. PMID- 9985571 TI - Effect of lattice contraction on the Raman shifts of CdSe quantum dots in glass matrices. PMID- 9985572 TI - Dislocation theory of vibrational excitations in small-angle grain boundaries. PMID- 9985573 TI - Nonlinear viscoelasticity determined from internal friction. PMID- 9985575 TI - Spin waves in the antiferromagnet perovskite LaMnO3: A neutron-scattering study. PMID- 9985574 TI - Itinerant-to-localized electron transition in CaRu1-xSnxO3 and SrRu1-xPbxO3. PMID- 9985576 TI - Magnetic vortex mass in two-dimensional easy-plane magnets. PMID- 9985578 TI - Magnetic impurity coupled to a quantum spin chain: A quantum Monte Carlo study. PMID- 9985577 TI - Spiral phase and spin waves in the quasi-two-dimensional antiferromagnet Ba2CuGe2O7. PMID- 9985579 TI - Spin fluctuations in itinerant electron antiferromagnetism and anomalous properties of Y(Sc)Mn2. PMID- 9985580 TI - Non-Fermi-liquid behavior in an extended Anderson model. PMID- 9985581 TI - Finite-size effects in a metallic multichannel ring with Kondo impurity: Persistent currents and magnetoresistance. PMID- 9985582 TI - Spin waves in antiferromagnetic thin films and multilayers: Surface and interface exchange and entire-cell effective-medium theory. PMID- 9985583 TI - Formation, propagation, reflection, and collision of microwave envelope solitons in yttrium iron garnet films. PMID- 9985584 TI - Critical behavior of the uniaxial ferromagnetic monolayer Fe(110) on W(110). PMID- 9985585 TI - X-ray-scattering study of the two magnetic correlation lengths in uranium antimonide. PMID- 9985586 TI - Magnetic disaccommodation phenomena in rare-earth intermetallic compounds. PMID- 9985587 TI - Dynamic susceptibility of a strong random anisotropy magnet. PMID- 9985588 TI - Magnetism of HgSe:Fe. PMID- 9985589 TI - High-frequency domain wall excitations in magnetic garnet films with in-plane magnetization. PMID- 9985590 TI - Field-dependent thermoelectric power and thermal conductivity in multilayered and granular giant magnetoresistive systems. PMID- 9985591 TI - Oxygen vacancies in BaTiO3. PMID- 9985592 TI - Recovery of nuclear magnetization under extreme inhomogeneous broadening. PMID- 9985593 TI - Magnetic properties and colossal magnetoresistance of La(Ca)MnO3 materials doped with Fe. PMID- 9985595 TI - Modification of the magnetic-field dependence of the Peierls transition by a magnetic chain. PMID- 9985594 TI - Structural changes and related effects due to charge ordering in Nd0.5Ca0.5MnO3. PMID- 9985596 TI - Effects of band structure and spin-independent disorder on conductivity and giant magnetoresistance in Co/Cu and Fe/Cr multilayers. PMID- 9985598 TI - Transport properties of Co-Ni superlattices. PMID- 9985597 TI - Hall effect and thermoelectric power in UNiGa. PMID- 9985599 TI - Electronic and magnetic properties of single-crystal YNi2B2C from 11B and 89Y NMR and magnetic-susceptibility measurements. PMID- 9985600 TI - Temperature dependence of the magnetic circular dichroism of the c(2 x 2) Mn/Ni (100) surface alloy. PMID- 9985601 TI - Angle-resolved x-ray circular and magnetic circular dichroisms: Definitions and applications. PMID- 9985602 TI - Theory of the charged Bose gas: Bose-Einstein condensation in an ultrahigh magnetic field. PMID- 9985603 TI - Vortex pinning by cylindrical defects in type-II superconductors: Numerical solutions to the Ginzburg-Landau equations. PMID- 9985604 TI - Minisubbands in electron excitation spectra of layered short-coherence-length superconductors. PMID- 9985605 TI - Heavy quasiparticles and Cooper-pair interaction in the Hubbard model. PMID- 9985606 TI - Electromagnetic response of the gauge-field model. PMID- 9985607 TI - Effects of 3.1-MeV proton and 1-GeV Au-ion irradiation on the magnetic flux noise and critical current of YBa2Cu3O7- delta. PMID- 9985608 TI - Thermally activated escape from the zero-voltage state in long Josephson junctions. PMID- 9985609 TI - Magnetic force acting on a magnetic dipole over a superconducting thin film. PMID- 9985610 TI - Nucleation, pinning, and flow of vortices in Josephson-junction arrays with defects. PMID- 9985611 TI - Magnetic field decoupling and 3D-2D crossover in Nb/Cu multilayers. PMID- 9985613 TI - Role of anisotropic impurity scattering in anisotropic superconductors. PMID- 9985612 TI - Microstructural properties of Bi2Sr2Can-1CunOy multilayers grown by molecular beam epitaxy. PMID- 9985614 TI - Force-balance equation for a pinned lattice of Abrikosov vortices. PMID- 9985615 TI - Interplay among critical temperature, hole content, and pressure in the cuprate superconductors. PMID- 9985616 TI - c-axis ac susceptibility in high-Tc superconductors. PMID- 9985617 TI - Cumulant approach to weakly doped antiferromagnets. PMID- 9985618 TI - Nonlinear microwave absorption in weak-link Josephson junctions. PMID- 9985619 TI - Nonlinear transverse magnetic moment in anisotropic superconductors. PMID- 9985621 TI - Angular dependence of the irreversible magnetization of YBa2Cu3O7 superconducting thin films. PMID- 9985620 TI - Surface impedance of YBa2Cu3O7/Y0.6Pr0.4Ba2Cu3O7 bilayers: Possible evidence for the proximity effect. PMID- 9985622 TI - One-dimensional Brownian-motion model for transport measurements in high temperature superconductors. PMID- 9985623 TI - Origin of the irreversibility line in thin YBa2Cu3O7- delta films with and without columnar defects. PMID- 9985625 TI - Comment on "Observation of a possible oxygen isotope effect on the effective mass of carriers in YBa2Cu3O6.94" PMID- 9985624 TI - Strong dependence on doping of a low-activation-energy relaxation process in YBa2Cu3O6+x: Possible polaron relaxation. PMID- 9985626 TI - Reply to "Comment on 'Observation of a possible oxygen isotope effect on the effective mass of carriers in YBa2Cu3O6.94' " PMID- 9985627 TI - Erratum: Electronic Raman scattering in superconductors as a probe of anisotropic electron pairing PMID- 9985628 TI - Erratum: Symmetry dependence of phonon line shapes in superconductors with anisotropic gaps PMID- 9985629 TI - Erratum: Evolution from the vortex state to the critical state in a square columnar Josephson-junction array PMID- 9985630 TI - Erratum: Symmetry of trapped-field profiles in square columnar Josephson-junction arrays PMID- 9985632 TI - Evidence of a structural transition of the sixfold molybdenum coordination in the oxides: A statistical approach. PMID- 9985631 TI - Infrared absorption study of the hydrogen-bond symmetrization in ice to 110 GPa. PMID- 9985633 TI - Transferable model for the atomistic simulation of Al2O3. PMID- 9985634 TI - Growth phenomenon in amorphous solids irradiated with GeV heavy ions: Electronic energy-loss dependence of the initial growth rate. PMID- 9985635 TI - Behavior of the elastic properties near an intermediate phase transition in Ni2MnGa. PMID- 9985636 TI - Theory of nonclassical surface nucleation at change of volume transitions. PMID- 9985638 TI - Third-order dielectric susceptibility in a model quantum paraelectric. PMID- 9985637 TI - Phase transitions in lithium ammonium sulfate below room temperature: An ultrasonic study. PMID- 9985639 TI - Scintillation and ionization in allene-doped liquid argon irradiated with 18O and 36Ar ions of 30 MeV/u. PMID- 9985640 TI - Phase diagram of carbon at high pressures and temperatures. PMID- 9985642 TI - Three-dimensional model of quasicrystalline atomic structure. PMID- 9985641 TI - Molecular-dynamics study of thermodynamical properties of liquid copper. PMID- 9985643 TI - Fluctuation-dissipation theorem for frequency-dependent specific heat. PMID- 9985644 TI - Geometrical confinement and cooperativity in supercooled liquids studied by solvation dynamics. PMID- 9985645 TI - Anomalous behavior of the longitudinal mode Gruneisen parameter around the glass transition as revealed by Brillouin spectroscopy: Polyvinylacetate. PMID- 9985646 TI - Computational materials synthesis. I. A tight-binding scheme for hydrocarbons. PMID- 9985647 TI - Computational materials synthesis. II. A study of polymerization. PMID- 9985648 TI - Computational materials synthesis. III. Synthesis of hydrogenated amorphous carbon from molecular precursors. PMID- 9985649 TI - Site identification of protons in SrTiO3: Mechanism for large protonic conduction. PMID- 9985651 TI - Cooling-rate effects in amorphous silica: A computer-simulation study. PMID- 9985650 TI - Resonant and phonon-assisted excitation energy transfer in the R1 line of PMID- 9985652 TI - Perturbative renormalization group, exact results, and high-temperature series to order 21 for the N-vector spin models on the square lattice. PMID- 9985653 TI - Microscopic origin of dimerization in the CuO2 chains in Sr14Cu24O41. PMID- 9985654 TI - Presence of midgap states in CaV4O9. PMID- 9985656 TI - Specific heat of the quantum Heisenberg antiferromagnet by a renormalization group approach. PMID- 9985655 TI - Dynamic critical exponents and sample independence times for the classical Heisenberg model. PMID- 9985657 TI - Pairing and phase separation in a one-dimensional spin-bag liquid. PMID- 9985658 TI - Cavity-fields approach to a simple model of axial quadrupolar glass. PMID- 9985659 TI - Magnetic phase transitions in the UFe1-xCoxAl system. PMID- 9985660 TI - Numerical renormalization-group study of a Kondo hole in a one-dimensional Kondo insulator. PMID- 9985661 TI - Magnetic phases of CsCuCl3: Anomalous critical behavior. PMID- 9985662 TI - Neutron study of the frustrated spinel compound Mg1+tFe2-2tTitO4 (t=0.55). PMID- 9985663 TI - Magnetic structure and anisotropy of thin Fe films on Cu(001) substrates. PMID- 9985664 TI - Effects of the surface and interface on the magneto-optical properties in (Co, Ni)/Cu(001) ultrathin films. PMID- 9985665 TI - Magnetoresistance and magnetization of Fe/Cr(001) superlattices with noncollinear magnetic ordering. PMID- 9985666 TI - Crystal and magnetic structures of the colossal magnetoresistance manganates Sr2 xNd1+xMn2O7 (x=0.0, 0.1). PMID- 9985667 TI - Microscopic model of dispersive-motion relaxation. PMID- 9985668 TI - Electric-field gradient at the Fe nucleus in epsilon -FeSi. PMID- 9985669 TI - Self-consistency and symmetry in d dimensions. PMID- 9985670 TI - Line of multicritical Lifshitz points in the phase diagram of MnP. PMID- 9985671 TI - Time-integrated nuclear resonant forward scattering of synchrotron radiation. PMID- 9985672 TI - X-ray resonant Raman scattering in the rare earths. PMID- 9985673 TI - Vortex lines in the three-dimensional XY model with random phase shifts. PMID- 9985674 TI - Rapid suppression of the spin gap in Zn-doped CuGeO3 and SrCu2O3. PMID- 9985676 TI - Magnetoresistance of the spin-state-transition compound La1-xSrxCoO3. PMID- 9985675 TI - Magnetoresistive effects associated with the field-induced suppression of the antiferromagnetic transition in Ce(Fe0.92Ru0.08)2. PMID- 9985677 TI - Pauli limiting of the upper critical magnetic field for d-wave superconductors. PMID- 9985679 TI - Solvable model for an impurity spin coupled to a one-dimensional superconductor. PMID- 9985678 TI - Temperature, current, and magnetic-field dependence of the activation energy in the vortex-glass phase of (K,Ba)BiO3 single crystals. PMID- 9985681 TI - Temperature and magnetic-field dependence of the superconducting order parameter in Zn studied by point-contact spectroscopy. PMID- 9985680 TI - Equilibrium properties of a Josephson-junction ladder with screening effects. PMID- 9985682 TI - Critical current and self-consistent order parameter of a superconductor-normal metal-superconductor junction. PMID- 9985684 TI - 13C NMR line-shape studies of the organic superconductor kappa -(ET)2Cu PMID- 9985683 TI - Inducing the paramagnetic Meissner effect in Nb disks by surface ion implantation. PMID- 9985685 TI - Spatiotemporal dynamics and plastic flow of vortices in superconductors with periodic arrays of pinning sites. PMID- 9985687 TI - Electronic structure and electron-phonon coupling in stoichiometric and defective hydrides MPdH3 (M=Ca, Sr, Eu, Yb). PMID- 9985686 TI - Heat capacity of pancake vortices in layered superconductors. PMID- 9985688 TI - Superfluid-Bose-glass transition in weakly disordered commensurate one dimensional system. PMID- 9985689 TI - Quantum cavitation in liquid helium. PMID- 9985690 TI - Exponentially tapered Josephson flux-flow oscillator. PMID- 9985691 TI - Oxygen distribution, incommensurate modulation, and structural disorder in Bi2Sr2Ca1-yYyCu2O8+ delta and Bi10Sr15Fe10O46 single crystals. PMID- 9985692 TI - Magnetic properties: Mossbauer, x-ray absorption spectroscopy, and specific-heat studies of Pr1.5Ce0.5MSr2Cu2Oz (M=Ta, In, Nb, Nb+Ga) compounds. PMID- 9985693 TI - Ginzburg-Landau theory of defects in d-wave superconductors. PMID- 9985695 TI - Quantum Monte Carlo evidence for d-wave pairing in the two-dimensional Hubbard model at a van Hove singularity. PMID- 9985694 TI - Bilayer coupling in the yttrium-barium family of high-temperature superconductors. PMID- 9985696 TI - I-V characteristics of Josephson-coupled layered superconductors with longitudinal plasma excitations. PMID- 9985697 TI - Density-functional theory of flux-lattice melting in high-Tc superconductors. PMID- 9985698 TI - Vortex pinning in Bi2Sr2CaCu2O8 tapes irradiated by ions. PMID- 9985699 TI - Anisotropy of flux dynamics for YBa2Cu3O7. PMID- 9985700 TI - d-wave superconductivity near charge instabilities. PMID- 9985702 TI - Changes of the local oxygen content and ordering at twin boundaries of high-Tc YBa2Cu3O7-x superconductors. PMID- 9985701 TI - Oxygen content and superconductivity in Y0.8Ca0.2Ba2Cu3Oy (y=6.03-6.89). PMID- 9985703 TI - Transport properties of an engineered PMID- 9985704 TI - Synthesis and characterization of single crystals of the superconductors Hg0.8Bi0.2Ba2Can-1CunO2n+2+ delta (n=2,3). PMID- 9985705 TI - Spin dynamics in the Nd2-xCexCuO4 system: Estimation of the rate of spin fluctuations. PMID- 9985706 TI - Oxygen diffusion in epitaxial GdBa2Cu3O7- delta thin films. PMID- 9985708 TI - Structure and properties of microporous titanosilicate determined by first principles calculations. PMID- 9985707 TI - Direct observation of the current distribution in thin superconducting strips using magneto-optic imaging. PMID- 9985709 TI - Raman excitations and orientational ordering in deuterium at high pressure. PMID- 9985710 TI - Systematic approach to generate near-perfect periodic continuous random network models: Application to amorphous Si3N4. PMID- 9985711 TI - Local structure and symmetry elements of the decagonal quasicrystal Al70Co15Ni15. PMID- 9985712 TI - High-pressure Raman spectroscopy of solid oxygen. PMID- 9985713 TI - Evidence of magnetization-dependent polaron distortion in La1-xAxMnO3, A=Ca, Pb. PMID- 9985714 TI - Thermodynamic properties of the incommensurate phase of CuGeO3. PMID- 9985715 TI - Stabilization of local moments in gapless Fermi systems. PMID- 9985716 TI - Magnetic dichroism in photoemission as a spin-resolving probe for electronic correlations. PMID- 9985717 TI - Cation disorder and size effects in magnetoresistive manganese oxide perovskites. PMID- 9985718 TI - Magnetic ordering in the S=1/2 quasi-one-dimensional compound La6Ca8Cu24O41. PMID- 9985719 TI - Grain-boundary effects on the magnetoresistance properties of perovskite manganite films. PMID- 9985720 TI - Optical observation of the interplay between magnetic and elastic energy in a spin-Peierls system. PMID- 9985721 TI - X-ray magnetic circular dichroism at the iron K edge in rare-earth-transition metal intermetallics: Experimental probe of the rare-earth magnetic moment. PMID- 9985722 TI - Quantum Monte Carlo study of the pairing correlation in the Hubbard ladder. PMID- 9985723 TI - Simulating the time-dependent dx2-y2 Ginzburg-Landau equations using the finite element method. PMID- 9985724 TI - Evidence for a quantum-vortex-liquid regime in ultrathin superconducting films. PMID- 9985726 TI - Coulomb correlations and pseudogap effects in a preformed pair model for the cuprates. PMID- 9985725 TI - Superconductivity of fcc fullerides containing off-centered octahedral cations. PMID- 9985727 TI - Dimensional crossover in the magnetic phase diagram of Bi2.15Sr1.85CaCu2O8+ delta crystals with different oxygen stoichiometry. PMID- 9985728 TI - Anomalous superconducting state gap size versus Tc behavior in underdoped Bi2Sr2Ca1-xDyxCu2O8+ delta. PMID- 9985729 TI - Rapid suppression of the superconducting gap in overdoped Bi2Sr2CaCu2O8+ delta. PMID- 9985730 TI - Random-matrix theory of impurity band tails. PMID- 9985731 TI - Analytic solution for the ground-state energy of the extensive many-body problem. PMID- 9985732 TI - Simplex method for calculating two-particle spectral densities in two-dimensional interacting electron systems. PMID- 9985733 TI - Population analysis of plane-wave electronic structure calculations of bulk materials. PMID- 9985734 TI - Calculated high-pressure-induced electronic and structural phase transitions in Sr and Yb up to 50 kbar. PMID- 9985735 TI - Electronic structure, cohesive properties, and phase stability of crystalline metastable phases in Ni-Mo systems. PMID- 9985736 TI - Resonant photoemission study of pyrite-type NiS2, CoS2 and FeS2. PMID- 9985738 TI - RKKY interaction and Kondo screening cloud for strongly correlated electrons. PMID- 9985737 TI - Role of edge electron states in the formation of edge magnetoplasmons. PMID- 9985740 TI - Nonequilibrium carrier-carrier scattering in two-dimensional carrier systems. PMID- 9985739 TI - Frequency locking and nonlocal transport in charge-density-wave conductors. PMID- 9985741 TI - Nonlinear susceptibility of periodic composites with shell structure. PMID- 9985742 TI - Experimental evaluation of the electron-intramolecular-vibration coupling constants of tetramethyltetrathiafulvalene. PMID- 9985744 TI - X-ray resonant Raman scattering in NiO: Resonant enhancement of the charge transfer excitations. PMID- 9985743 TI - Effect of interchain separation on the photoinduced absorption spectra of polycarbazolyldiacetylenes. PMID- 9985745 TI - Bipolaron-induced third-order optical nonlinearity in conjugated conducting polymers. PMID- 9985747 TI - Raman scattering from optical phonons in InAs1-xSbx/InAs strained-layer superlattices. PMID- 9985746 TI - Binding energy for the intrinsic excitons in wurtzite GaN. PMID- 9985748 TI - X-ray-reflectivity study of Ge-Si-Ge films. PMID- 9985749 TI - X-ray-diffraction study of size-dependent strain in quantum-wire structures. PMID- 9985750 TI - Dynamical simulation of optical phonon transfer in the GaAs/AlxGa1-xAs/GaAs single-barrier structure. PMID- 9985751 TI - Stokes shift in quantum wells: Trapping versus thermalization. PMID- 9985752 TI - Valley splitting in triangular Si(001) quantum wells. PMID- 9985753 TI - Even-odd filling-factor switching in one-dimensional lateral superlattices. PMID- 9985754 TI - Resonant magnetotunneling through individual self-assembled InAs quantum dots. PMID- 9985755 TI - Hydrogenic impurities in a quantum well wire in intense, high-frequency laser fields. PMID- 9985756 TI - Edge and bulk transport in variably connected quantum Hall conductor. PMID- 9985757 TI - Quantum Hall transitions in (TMTSF)2PF6. PMID- 9985758 TI - Effect of Coulomb enhancement on optical gain in (Zn,Cd)Se/ZnSe multiple quantum wells. PMID- 9985759 TI - Photoluminescence properties of surface-oxidized Ge nanocrystals: Surface localization of excitons. PMID- 9985760 TI - Coherence transfer via resonance Rayleigh scattering of exciton polaritons in a semiconductor microcavity. PMID- 9985761 TI - Spatial dependence of the strain-induced coupling in highly strained quantum wells. PMID- 9985763 TI - Equilibrium shape equation and possible shapes of carbon nanotubes. PMID- 9985762 TI - Composite fermions on a Haldane sphere: Quasielectron-quasihole symmetry. PMID- 9985764 TI - Mechanism for island formation during low-temperature growth on (100) surfaces of fcc metals. PMID- 9985765 TI - Adsorption sites and surface vibrations of the Cu(110)-(2 x 3)-N surface. PMID- 9985766 TI - Picosecond photoluminescence decay of Si-doped chemical-vapor-deposited diamond films. PMID- 9985767 TI - Localized electromagnetic modes in nonlinear superlattices. PMID- 9985768 TI - Exponential scaling of sputtered negative-ion yields with transient work-function changes on Cs+-bombarded surfaces. PMID- 9985769 TI - Strain-induced distortion of the bulk bands of gadolinium. PMID- 9985771 TI - Linear-response theory and lattice dynamics: A muffin-tin-orbital approach. PMID- 9985770 TI - Optimal basis sets for detailed Brillouin-zone integrations. PMID- 9985773 TI - KKR-ASA method in exact exchange-potential band-structure calculations. PMID- 9985772 TI - Electron-phonon interactions and related physical properties of metals from linear-response theory. PMID- 9985774 TI - Robust localized-orbital transferability using the Harris functional. PMID- 9985776 TI - Generalized gradient approximation for the exchange-correlation hole of a many electron system. PMID- 9985775 TI - One-particle spectral weight of the three-dimensional single-band Hubbard model. PMID- 9985777 TI - Electron energy spectra of one-dimensional nondiagonal nonperiodic lattices. PMID- 9985778 TI - Electronic structure of normal, inverse, and partially inverse spinels in the MgAl2O4 system. PMID- 9985779 TI - Effect of dispersion in the f band of the one-dimensional Anderson lattice model. PMID- 9985781 TI - Hydrostatic pressure effects on the free and self-trapped exciton states in CsI. PMID- 9985780 TI - Metal-insulator transition in oxygen-deficient LaNiO3-x perovskites. PMID- 9985782 TI - Searches for charge-density waves in the alkali metals: Recent neutron-scattering results for sodium. PMID- 9985783 TI - Electron-phonon scattering contributions to metallic resistivity at 0 K. PMID- 9985784 TI - High-temperature thermopower of LaMnO3 and related systems. PMID- 9985785 TI - Magnetoimpurity theory of resistivity and magnetoresistance for degenerate ferromagnetic semiconductors of the LaMnO3 type. PMID- 9985786 TI - Ultraviolet photorefraction and the superionic phase transition of alpha -LiIO3. PMID- 9985787 TI - Auger decay of degenerate and Bose-condensed excitons in Cu2O. PMID- 9985788 TI - Photoinduced conversion of optically active defects in germanium-doped silica. PMID- 9985790 TI - Nonlinear Berry phases for simple band representations. II. Bloch and Wannier functions composed of Gaussian orbitals. PMID- 9985789 TI - Oxygen 1s x-ray-absorption near-edge structure of Zn-Ni ferrites: A comparison with the theoretical calculations. PMID- 9985791 TI - Thermopower and high-pressure electrical conductivity measurements of template synthesized polypyrrole. PMID- 9985793 TI - Spin-density-wave instabilities for imperfectly nested Fermi surfaces: Application to BEDT-TTF salts. PMID- 9985792 TI - Carbon atomic chains in strong electric fields. PMID- 9985794 TI - Valence band of LiNixMn2-xO4 and its effects on the voltage profiles of LiNixMn2 xO4/Li electrochemical cells. PMID- 9985795 TI - Ab initio study of oxygen point defects in GaAs, GaN, and AlN. PMID- 9985796 TI - Ion-beam processing of silicon at keV energies: A molecular-dynamics study. PMID- 9985798 TI - Local relaxations and electric-field gradient at the Cd site in heavily doped Si:Cd. PMID- 9985797 TI - Energy-level dynamics of deep gap states in hydrogenated amorphous silicon under illumination. PMID- 9985799 TI - Luminescence-intensity kinetics due to nonradiative capture by multiphonon emission in highly excited CdS and CdSe crystals. PMID- 9985800 TI - Higher-interband electroreflectance of long-range ordered Ga0.5In0.5P. PMID- 9985801 TI - Nitrogen interstitials in diamond. PMID- 9985802 TI - Pulse-propagation-induced higher orders of diffraction in transient four-wave mixing with semiconductors. PMID- 9985804 TI - Geometry and electronic structure of GaAs(001)(2 x 4) reconstructions. PMID- 9985803 TI - Traveling carrier-density waves in n-type GaAs at low-temperature impurity breakdown. PMID- 9985806 TI - Higher-order results for the relation between channel conductance and the Coulomb blockade for two tunnel-coupled quantum dots. PMID- 9985805 TI - Far-infrared absorption in parallel quantum wires with weak tunneling. PMID- 9985807 TI - Electronic structure of imperfect Si/Ge heterostructures. PMID- 9985808 TI - Energy levels of D0 and D- in graded quantum-well structures of GaAs/Ga1-xAlxAs under magnetic fields. PMID- 9985809 TI - Dynamical phenomena in Fibonacci semiconductor superlattices. PMID- 9985810 TI - Deep-level transient spectroscopy study of narrow SiGe quantum wells with high Ge content. PMID- 9985811 TI - Plasmon modes and correlation functions in quantum wires and Hall bars. PMID- 9985812 TI - Resonant tunneling through ultrasmall quantum dots: Zero-bias anomalies, magnetic field dependence, and boson-assisted transport. PMID- 9985813 TI - Skyrmions in the quantum Hall effect at finite Zeeman coupling. PMID- 9985814 TI - Skyrmions and edge-spin excitations in quantum Hall droplets. PMID- 9985815 TI - Size-dependent transmission coefficients of edge channels in the quantum-Hall regime. PMID- 9985816 TI - Quasiholes and fermionic zero modes of paired fractional quantum Hall states: The mechanism for non-Abelian statistics. PMID- 9985817 TI - Charged pseudospin textures in double-layer quantum Hall systems: Bimerons and meron crystals. PMID- 9985818 TI - Bulk versus edge in the quantum Hall effect. PMID- 9985819 TI - Quantum confinement effects above the fundamental band gap in HgTe/Hg0.3Cd0.7Te heterostructures studied by resonant Raman scattering near the E1 edge. PMID- 9985820 TI - Two-dimensional excitonic emission in InAs submonolayers. PMID- 9985821 TI - Raman-spectroscopy investigations of photoinduced changes of the spatial charge carrier distribution in p-type modulation-doped quantum-well structures. PMID- 9985822 TI - Electro-optic exciton nonlinearities in Zn1-xCdxSe/ZnSe multiple quantum wells. PMID- 9985824 TI - Exciton localization and decomposition dynamics in cuprous halide nanocrystals. PMID- 9985823 TI - Magneto-optical study of interwell coupling in double quantum wells using diluted magnetic semiconductors. PMID- 9985825 TI - Coverage-dependent thermal reactions of digermane on Si(100)-(2 x 1). PMID- 9985826 TI - Semiconducting Mg2Si thin films prepared by molecular-beam epitaxy. PMID- 9985827 TI - Ballistic-electron-emission spectroscopy of Au/Si and Au/GaAs interfaces: Low temperature measurements and ballistic models. PMID- 9985828 TI - Electric-field-dependent intersubband transition via optical phonons in a doped thin-layer inserted quantum-well structure. PMID- 9985829 TI - Exciton properties in p-type GaAs/AlxGa1-xAs quantum wells in the high doping regime. PMID- 9985830 TI - Excitons bound at interacting acceptors in AlxGa1-xAs/GaAs quantum wells. PMID- 9985832 TI - Theory of electronic and optical properties of magnetoexcitons in quantum-well wires. PMID- 9985831 TI - Center of mass quantization of excitons in Zn1-xCdxSe/ZnSe quantum-wells. PMID- 9985833 TI - Magnetoconductance fluctuations in a strongly correlated disordered ring system at low temperatures. PMID- 9985834 TI - Properties of lateral Nb contacts to a two-dimensional electron gas in an In0.77Ga0.23As/InP heterostructure. PMID- 9985835 TI - Scattering theory of subsurface impurities observed in scanning tunneling microscopy. PMID- 9985836 TI - Surface mobility of Ag on Pd(100) measured by specular helium scattering. PMID- 9985837 TI - Molecular-dynamics study on the equilibrium structure and the stability of a cluster dimer. PMID- 9985838 TI - Size dependence of the lattice parameter for Pd clusters: A molecular-dynamics study. PMID- 9985840 TI - Molecular orientational vibrations in monolayer systems. PMID- 9985839 TI - Inhibition of step-flow crystal growth on the {110} face of alpha -HgI2 by a high coverage factor. PMID- 9985841 TI - Adsorbate-atom-induced relaxation of thin Li(001) films. PMID- 9985843 TI - Pokrovsky-Talapov commensurate-incommensurate transition in the CO/Pd(100) system. PMID- 9985842 TI - Modeling of Ir adatoms on Ir surfaces. PMID- 9985845 TI - Growth and electronic structure of thin epitaxial Pd and Co films on W(100). PMID- 9985846 TI - Thermally induced core-electron binding-energy shifts in transition metals: An experimental investigation of Ta(100). PMID- 9985844 TI - Adsorption isotherm study of multilayer N2 films on BN. PMID- 9985847 TI - Quantum-well states and the short period of oscillation in Cu/Co(001) multilayers. PMID- 9985848 TI - c-axis resistivity of MoCl5 graphite intercalation compounds. PMID- 9985849 TI - Initial stages of cesium incorporation on keV-Cs+-irradiated surfaces: Positive ion emission and work-function changes. PMID- 9985850 TI - Phenomenological electronic stopping-power model for molecular dynamics and Monte Carlo simulation of ion implantation into silicon. PMID- 9985851 TI - Contribution of charge-transfer processes to ion-induced electron emission. PMID- 9985852 TI - Resonant charge transfer in grazing scattering of alkali-metal ions from an Al(111) surface. PMID- 9985854 TI - Surprises in the orbital magnetic moment and g factor of the dynamic Jahn-Teller ion C60- PMID- 9985853 TI - Chemistry and kinetics of the interaction of hydrogen atoms with (100) InP surfaces: An in situ real-time ellipsometric study. PMID- 9985856 TI - Diffusion Monte Carlo study of jellium surfaces: Electronic densities and pair correlation functions. PMID- 9985855 TI - Multiplet structure in high-resolution and spin-resolved x-ray photoemission from gadolinium. PMID- 9985857 TI - Local binding trend and local electronic structures of 4d transition metals. PMID- 9985858 TI - Dielectric properties of orientationally ordered/disordered C60(111) films. PMID- 9985859 TI - Erratum: Surface structure of epitaxial Gd(0001) films on W(110) studied by quantitative LEED analysis PMID- 9985860 TI - Erratum: Theory of the thermoelectric power or Seebeck coefficient: The case of phonon scattering for a degenerate free-electron gas PMID- 9985861 TI - Erratum: Band-structure parameters by genetic algorithm PMID- 9985862 TI - Optical properties and electronic structures of equiatomic XTi (X=Fe, Co, and Ni) alloys. PMID- 9985863 TI - Straightforward gradient approximation for the exchange energy of s-p bonded solids. PMID- 9985864 TI - Gradient expansion of the exchange energy from second-order density response theory. PMID- 9985865 TI - One-dimensional pair hopping and attractive Hubbard models: A comparative study. PMID- 9985866 TI - Effect of finite impurity mass on the Anderson orthogonality catastrophe in one dimension. PMID- 9985867 TI - Conduction in LaCoO3 by small-polaron hopping below room temperature. PMID- 9985868 TI - Comparison of the temperature-dependent electronic structure of the perovskites La0.65A0.35MnO3 (A=Ca,Ba). PMID- 9985870 TI - Semiempirical local-field correction function for electrons in Li metal. PMID- 9985869 TI - Theory of electronic ferroelectricity. PMID- 9985872 TI - Use of polarized optical absorption to obtain structural information for Na+/Nd3+ beta "-alumina. PMID- 9985871 TI - Electrical properties of NiS2-xSex single crystals: From Mott insulator to paramagnetic metal. PMID- 9985873 TI - Charge transfer in alkali-metal-doped polymeric fullerenes. PMID- 9985874 TI - Photon-echo attenuation in rare-earth-ion-doped crystals. PMID- 9985875 TI - Radiative and nonradiative processes in the optical cycle of the F3+ center in LiF. PMID- 9985876 TI - Photoelectron spectroscopy of strongly correlated Yb compounds. PMID- 9985877 TI - Towards a self-consistent random-phase approximation for Fermi systems. PMID- 9985878 TI - Confinement and transverse conductivity in coupled Luttinger liquids. PMID- 9985879 TI - Numerical results for generalized resonating-valence-bond wave functions: Application to the Hubbard model. PMID- 9985881 TI - Localization and percolation in semiconductor alloys: GaAsN vs GaAsP. PMID- 9985880 TI - 3d semicore states in ZnSe, GaAs, and Ge. PMID- 9985882 TI - Electronic and optical properties of unstrained and strained wurtzite GaN. PMID- 9985884 TI - Formation of bound excitons by photoexcited carriers in p-type GaAs revealed by picosecond luminescence spectroscopy. PMID- 9985883 TI - Band structure of CdS and CdSe at high pressure. PMID- 9985885 TI - Defect-related optical transitions in GaN. PMID- 9985886 TI - Electroluminescence of erbium-doped silicon. PMID- 9985888 TI - Semiconductor noise in the framework of semiclassical transport. PMID- 9985887 TI - Direct-gap reduction and valence-band splitting of ordered indirect-gap AlInP2 studied by dark-field spectroscopy. PMID- 9985889 TI - Charge separation and transport in conjugated-polymer/semiconductor-nanocrystal composites studied by photoluminescence quenching and photoconductivity. PMID- 9985891 TI - Roughening and ripple instabilities on ion-bombarded Si. PMID- 9985890 TI - Atomic structure and faulted boundaries in the GaAs(001) beta (2 x 4) surface as derived from x-ray diffraction and line-shape analysis. PMID- 9985893 TI - First-principles pseudopotential calculations of passivated GaAs(001) surfaces. PMID- 9985892 TI - Intrinsic valence and conduction bands of Si(111)-1 x 1. PMID- 9985894 TI - Current and charge distributions of the fractional quantum Hall liquids with edges. PMID- 9985896 TI - Ultrafast energy relaxation in quantum dots. PMID- 9985895 TI - Dynamics of directly created excitons in asymmetric double quantum wells. PMID- 9985897 TI - Theory of coherent time-dependent transport in one-dimensional multiband semiconductor superlattices. PMID- 9985900 TI - Electron diffraction by periodic arrays of quantum antidots. PMID- 9985899 TI - Magnetotransport fluctuations in regular semiconductor ballistic quantum dots. PMID- 9985898 TI - Strong interaction of Fermi-edge singularity and exciton related to N=2 subband in a modulation-doped AlxGa1-xAs/InyGa1-yAs/GaAs quantum well. PMID- 9985901 TI - Tunneling escape time of electrons from the quasibound Stark localized states in ultrathin barrier GaAs/AlAs superlattices. PMID- 9985902 TI - Electron capture in quantum wells via scattering by electrons, holes, and optical phonons. PMID- 9985903 TI - Electronic energy levels and energy relaxation mechanisms in self-organized InAs/GaAs quantum dots. PMID- 9985904 TI - Strain-related phenomena in GaN thin films. PMID- 9985906 TI - Hydrogen microstructure in hydrogenated amorphous silicon. PMID- 9985905 TI - Edge-on micro-Raman assessment of trigonal modes in partially ordered GaInP2. PMID- 9985907 TI - Nanostructured GaN: Microstructure and optical properties. PMID- 9985909 TI - Theory of unconfined excitons trapped by a quantum well. PMID- 9985908 TI - Magnetopolaron-induced increase of the efficiency in two-LO-phonon Raman scattering from quantum wells. PMID- 9985910 TI - Exciton bound to an ionized donor impurity in semiconductor spherical quantum dots. PMID- 9985911 TI - Monte Carlo simulation of intersubband relaxation in wide, uniformly doped GaAs/AlxGa1-xAs quantum wells. PMID- 9985912 TI - Vibrational excitations in thin films studied by spatial dispersion Brillouin spectroscopy. PMID- 9985913 TI - Lasing in ZnSe/ZnS0.18Se0.82 superlattices. PMID- 9985914 TI - Integer quantum Hall effect with realistic boundary condition: Exact quantization and breakdown. PMID- 9985915 TI - Theory of optical-phonon limited hot-electron transport in quantum wires. PMID- 9985916 TI - Adsorbate-adsorbate interactions from statistical analysis of STM images: N/Ru(0001). PMID- 9985917 TI - Initial stages of Cu epitaxy on Ni(100): Postnucleation and a well-defined transition in critical island size. PMID- 9985918 TI - Evidence for the shear horizontal phonon mode on the NaCl(001) surface. PMID- 9985919 TI - Nitrogen-induced reconstruction of the Cu3Au(110) surface. PMID- 9985920 TI - Bias-dependent imaging of the In-terminated InAs(001) (4 x 2)/c(8 x 2) surface by STM: Reconstruction and transitional defect. PMID- 9985921 TI - Fractal surface dimension from cyclic I-V studies and atomic-force microscopy: Role of noncontiguous reaction sites. PMID- 9985922 TI - Local modification of Ag thin films on Si(100) by scanning tunneling microscopy. PMID- 9985923 TI - Monolayer-period oscillation of secondary electrons and its application for determining the polarization oscillation period in Au/Fe(110). PMID- 9985924 TI - Substitutional adsorption of Li on Al: The structure of the Al(111)-( sqrt 3 x sqrt 3)R30 degrees-Li phase. PMID- 9985926 TI - Adsorption strains in porous silicon. PMID- 9985925 TI - Influence of adsorption on thin film thermodynamics. PMID- 9985927 TI - Method for evaluation of the Ehrlich-Schwoebel barrier to interlayer transport in metal homoepitaxy. PMID- 9985928 TI - Temperature and orientation dependence of kinetic roughening during homoepitaxy: A quantitative x-ray-scattering study of Ag. PMID- 9985929 TI - Electronic-structure investigation of oxidized aluminum films with electron momentum spectroscopy. PMID- 9985930 TI - Edge state in graphene ribbons: Nanometer size effect and edge shape dependence. PMID- 9985931 TI - Magnetic dichroism in core-level x-ray photoemission with unpolarized excitation. PMID- 9985933 TI - Electronic structure of Pu compounds with group-IIIB metals: Two regimes of behavior. PMID- 9985932 TI - Phase transitions in a system of CH3(CH2)n-1 self-assembled on the Au(111) crystal surface. PMID- 9985935 TI - Density waves in a transverse electric field. PMID- 9985934 TI - Dynamical density-density correlations in one-dimensional Mott insulators. PMID- 9985937 TI - Long-mean-free-path ballistic hot electrons in high-purity GaAs. PMID- 9985936 TI - Electronic state of the organic salt (DI-DCNQI)2Ag, where DI-DCNQI is 2,5-diiodo N,N'-dicyanoquinonediimine. PMID- 9985938 TI - Influence of SiH4 deposition on the Si(111) 1 x 1-->7 x 7 phase transition. PMID- 9985940 TI - Exciton relaxation dynamics in quantum dots with strong confinement. PMID- 9985939 TI - Surfactant adsorption site and growth mechanism of Ge- on Ga-terminated Si(111). PMID- 9985941 TI - Hofstadter butterflies for flat bands. PMID- 9985942 TI - Ultrafast carrier dynamics on the Si(100)2 x 1 surface. PMID- 9985943 TI - Single-particle excitations and many-particle interactions in quantum wires and dots. PMID- 9985944 TI - Theoretical study of atomic and electronic structures of atomic wires on an H terminated Si(100)2 x 1 surface. PMID- 9985946 TI - Measurement of the conductance distribution function at a quantum Hall transition. PMID- 9985945 TI - Near-field optical spectroscopy of localized excitons in strained CdSe quantum dots. PMID- 9985947 TI - Comparing conductance quantization in quantum wires and quantum Hall systems. PMID- 9985948 TI - Universality and phase diagram around half-filled Landau levels. PMID- 9985949 TI - Temperature dependence of the spin polarization of a quantum Hall ferromagnet. PMID- 9985950 TI - Hybridization of single- and double-layer behavior in a double-quantum-well structure. PMID- 9985951 TI - Electronic structure of GaN measured using soft-x-ray emission and absorption. PMID- 9985952 TI - Spectrally resolved Overhauser shifts in single GaAs/AlxGa1-xAs quantum dots. PMID- 9985953 TI - Nonlinear intersubband absorption of a hot quasi-two-dimensional electron plasma studied by femtosecond infrared spectroscopy. PMID- 9985954 TI - Interaction of oxygen with a Cs-monolayer-covered Si(100) surface. PMID- 9985956 TI - Correlation between the scale-dependent fractal dimension of fracture surfaces and the fracture toughness. PMID- 9985955 TI - Energetics of AlN thin films and the implications for epitaxial growth on SiC. PMID- 9985957 TI - Exact island-size distributions for submonolayer deposition: Influence of correlations between island size and separation. PMID- 9985959 TI - Fully three-dimensional scattering calculations of standing electron waves in quantum nanostructures: The importance of quasiparticle interactions. PMID- 9985958 TI - The Ce 4f surface shift: A test for the Anderson-impurity Hamiltonian. PMID- 9985960 TI - Step-induced unusual magnetic properties of ultrathin Co/Cu films: Ab initio study. PMID- 9985962 TI - Linear-response calculation of the Coulomb pseudopotential micro* for Nb. PMID- 9985961 TI - Magnetic anisotropy in (110) epitaxial DyFe2 Laves phase. PMID- 9985963 TI - Magnetic character of the deformable jellium. PMID- 9985964 TI - Pseudopotentials including semicore states, with an application to barium, alpha cerium, and thorium. PMID- 9985965 TI - Distribution of level curvatures for the Anderson model at the localization delocalization transition. PMID- 9985967 TI - Quantum phase transition and long-range order in the ground state of a lattice of pseudospins coupled with optic phonons. PMID- 9985966 TI - Thermodynamics of metal-insulator systems: The two-fluid model in the presence of a magnetic field. PMID- 9985969 TI - Momentum-distribution critical exponents for the one-dimensional large-U Hubbard model in the thermodynamic limit. PMID- 9985968 TI - Effects of impurities and temperature on the thermal hysteresis of Ohmic resistance in Tl-doped blue bronze. PMID- 9985970 TI - Electronic structure and optical properties of the B12O2 crystal. PMID- 9985971 TI - Electronic structure, electronic decay, and desorption processes of molecular solid SiCl4 following core-level excitation. PMID- 9985972 TI - Defect-induced nucleation and growth of amorphous silicon. PMID- 9985973 TI - Calculations of the ground-state energy for strong- and intermediate-coupling exciton-phonon systems. PMID- 9985975 TI - Disorder and persistent photoconductivity in ZnxCd1-xSe semiconductor alloys. PMID- 9985974 TI - Magnetopolaron effect on shallow indium donors in CdTe. PMID- 9985976 TI - Large atomic displacements associated with the nitrogen antisite in GaN. PMID- 9985977 TI - Electrostatic tip-sample interaction in immersion force microscopy of semiconductors. PMID- 9985978 TI - Model-dependent electronic structure of the Si(111)2 x 1 surface. PMID- 9985979 TI - Defect-assisted relaxation in quantum dots at low temperature. PMID- 9985980 TI - Coupling between one-dimensional excitons and two-dimensional photons: Quantum wires in a microcavity. PMID- 9985981 TI - Electron scattering due to confined and extended acoustic phonons in a quantum wire. PMID- 9985982 TI - Electron interference due to localization paths in an Aharonov-Bohm ring. PMID- 9985983 TI - Reentrant resonant tunneling. PMID- 9985984 TI - Exchange interaction and phonon confinement in CdSe quantum dots. PMID- 9985985 TI - Single quantum dots as local probes of electronic properties of semiconductors. PMID- 9985986 TI - Quantum oscillation of the cyclotron mass in two-dimensional electron systems in silicon. PMID- 9985987 TI - Hysteretic voltage gap of a multijunction trap. PMID- 9985988 TI - Exact solution for charge solitons in two coupled one-dimensional arrays of small tunnel junctions. PMID- 9985989 TI - Quantum transport through periodically arranged magnetic barriers. PMID- 9985990 TI - Photon-assisted parity change and Andreev tunneling. PMID- 9985992 TI - Coherent patterns and self-induced diffraction of electrons on a thin nonlinear layer. PMID- 9985991 TI - Effect of uniaxial compression on quantum Hall plateaus and Shubnikov-de Haas oscillations in p-type GaAs/AlxGa1-xAs heterostructures. PMID- 9985993 TI - Direct observation of above-barrier quasibound states in InxGa1-xAs/AlAs/GaAs quantum wells. PMID- 9985995 TI - Investigation of niobium clusters: Bare and CO-adsorption. PMID- 9985994 TI - Optical absorption spectroscopy of Si-Ge alloys and superlattices. PMID- 9985996 TI - Molecular-dynamics study of collision, implantation, and fragmentation of Ag7 on Pd(100). PMID- 9985997 TI - Interactions between adsorbed Si dimers on Si(001). PMID- 9985998 TI - Group and energy velocities of acoustic surface waves in piezoelectrics. PMID- 9985999 TI - Observation of the Stranski-Krastanov growth transition in GdBa2Cu3O7- delta films. PMID- 9986000 TI - Generalized-gradient functionals in adaptive curvilinear coordinates. PMID- 9986001 TI - Calculation of the self-consistent-field electronic wave functions of crystals using Wannier-type functions: The case of LiH. PMID- 9986002 TI - Phase diagram of the extended Hubbard model at weak coupling. PMID- 9986003 TI - Microwave surface resistance of potassium in a perpendicular magnetic field: Effects of the charge-density wave. PMID- 9986004 TI - Electronic structure and magnetic properties of random alloys: Fully relativistic spin-polarized linear muffin-tin-orbital method. PMID- 9986005 TI - Electronic excitation spectra from ab initio band-structure results for LaMO3 (M=Cr,Mn,Fe,Co,Ni). PMID- 9986006 TI - Tight-binding treatment of the Hubbard model in infinite dimensions. PMID- 9986007 TI - Ground-state energy of the Hubbard model at half filling. PMID- 9986008 TI - Finite-U impurity Anderson model in the presence of an external magnetic field. PMID- 9986009 TI - Combining coupled-cluster and perturbative expansions through intermediate Hamiltonians: Theory and application to 1D and 2D spin lattices. PMID- 9986010 TI - Model for the electronic and vibronic structure of 4T1 levels of d 5 ions coupled to E vibrational modes: Case of the fluorescent level of Mn2+ in ZnS. PMID- 9986011 TI - Optical properties of the group-IVB refractory metal compounds. PMID- 9986012 TI - Experimental and theoretical study of the electronic structure of Fe, Co, and Ni aluminides with the B2 structure. PMID- 9986014 TI - Separable dual-space Gaussian pseudopotentials. PMID- 9986013 TI - Symmetrized projector quantum Monte Carlo studies of the ground state of C60. PMID- 9986015 TI - Coupled-mode calculation with the R-matrix propagator for the dispersion of surface waves on a truncated photonic crystal. PMID- 9986016 TI - Magnetostructural phase transitions in La1-xSrxMnO3 with controlled carrier density. PMID- 9986017 TI - Positron-annihilation investigation of vacancy agglomeration in electron irradiated float-zone silicon. PMID- 9986018 TI - Ab initio calculations of the cohesive, elastic, and dynamical properties of CoSi2 by pseudopotential and all-electron techniques. PMID- 9986019 TI - Ground state and excitations in polyacetylene chains. PMID- 9986020 TI - Spectroscopy and piezospectroscopy of the Lyman transitions and Fano resonances of indium in silicon. PMID- 9986021 TI - Deep donors in Cd1-xZnxTe:Cl. PMID- 9986022 TI - Dynamics of optical excitations in a ladder-type pi -conjugated polymer containing aggregate states. PMID- 9986023 TI - Field-dependent screening and dephasing in semiconductor Bloch equations. PMID- 9986024 TI - Nonequilibrium hole relaxation dynamics in an intrinsic semiconductor. PMID- 9986026 TI - Influence of polytypism on thermal properties of silicon carbide. PMID- 9986025 TI - Anisotropy of hole structures in polymers probed by two-dimensional angular correlation of annihilation radiation. PMID- 9986028 TI - Phase transformations and the nature of the semiconductor-to-metal transition in bulk a-GaSb and a-(Ge2)1-x(GaSb)x semiconductors under high pressure. PMID- 9986027 TI - High-field transport in model materials. PMID- 9986029 TI - Temperature dependence of the direct gaps of ZnSe and Zn0.56Cd0.44Se. PMID- 9986030 TI - dc-electric-field-induced second-harmonic generation in Si(111)-SiO2-Cr metal oxide-semiconductor structures. PMID- 9986031 TI - Electronic structure of InAs(1-bar 1-bar 1-bar)2 x 2 and InSb(1-bar 1-bar 1-bar)2 x 2 studied by angle-resolved photoelectron spectroscopy. PMID- 9986033 TI - Ground state of a two-dimensional electron liquid in a weak magnetic field. PMID- 9986032 TI - Tunneling studies of two-dimensional states in semiconductors with inverted band structure: Spin-orbit splitting and resonant broadening. PMID- 9986035 TI - Persistent magnetic moment of rotating mesoscopic rings and cylinders. PMID- 9986034 TI - Excitons in CdTe quantum wires with strain-induced lateral confinement. PMID- 9986036 TI - Boundary-element method for the calculation of electronic states in semiconductor nanostructures. PMID- 9986037 TI - Excited states and size-dependent electro-optical properties of CdSxSe1-x quantum dots. PMID- 9986038 TI - Energy band for manipulated atomic structures of Si, GaAs, and Mg on an insulating substrate. PMID- 9986039 TI - Envelope-function formalism for electrons in abrupt heterostructures with material-dependent basis functions. PMID- 9986041 TI - Short-range impurity in the vicinity of a saddle point and the levitation of the two-dimensional delocalized states in a magnetic field. PMID- 9986040 TI - Confinement effects and polarization dependence of luminescence from monolayer thick Ge quantum wells. PMID- 9986042 TI - Dynamical response of a one-dimensional quantum-wire electron system. PMID- 9986043 TI - Noninvasive determination of the ballistic-electron current distribution. PMID- 9986044 TI - Resonant tunneling through a coupled double quantum well in the presence of electron-phonon interaction. PMID- 9986046 TI - Spin relaxation of electrons in p-doped quantum wells via the electron-hole exchange interaction. PMID- 9986045 TI - Optical properties of arrays of quantum dots with internal disorder. PMID- 9986047 TI - Magnetic-field enhancement of the exciton-polariton splitting in a semiconductor quantum-well microcavity: The strong coupling threshold. PMID- 9986048 TI - Field effect on positron diffusion in semi-insulating GaAs. PMID- 9986049 TI - Optical properties of quantum wires: Fermi-edge singularity exponents and the low density limit. PMID- 9986050 TI - Equispaced-level Hamiltonians with the variable effective mass following the potential. PMID- 9986052 TI - Silicon spreading in delta -doped GaAs(100): A high-resolution electron-energy loss-spectroscopy study. PMID- 9986051 TI - Atomic structure and thermal stability of two-dimensional Er silicide on Si(111). PMID- 9986053 TI - Phonoconductivity measurement of the phonon absorption by a two-dimensional hole gas in a GaAs heterojunction. PMID- 9986054 TI - Determination of deformation potentials in ZnSe/GaAs strained-layer heterostructures. PMID- 9986055 TI - Polaritonic effects in superlattices. PMID- 9986056 TI - Effects of the screened exchange interaction on the tunneling and Landau gaps in double quantum wells. PMID- 9986057 TI - Magnetoplasmon excitations in double-quantum-well systems in a parallel magnetic field. PMID- 9986058 TI - Transport mechanism of Gamma - and X-band electrons in AlxGa1-xAs/AlAs/GaAs double-barrier quantum-well infrared photodetectors. PMID- 9986059 TI - Two representations of the current density in charge-transport problems. PMID- 9986060 TI - Distribution-function analysis of mesoscopic hopping conductance fluctuations. PMID- 9986061 TI - Reaction of I2 with the (001) surfaces of GaAs, InAs, and InSb. I. Chemical interaction with the substrate. PMID- 9986062 TI - Reaction of I2 with the (001) surfaces of GaAs, InAs, and InSb. II. Ordering of the iodine overlayer. PMID- 9986063 TI - Perturbation theory of diffuse RHEED applied to rough surfaces: Comparison with supercell calculations. PMID- 9986064 TI - Atomic-scale friction image of graphite in atomic-force microscopy. PMID- 9986065 TI - Energetical preference of diamond nanoparticles. PMID- 9986066 TI - Chemisorption of H on Pd(111): An ab initio approach with ultrasoft pseudopotentials. PMID- 9986067 TI - Phase boundaries of nanometer scale c(2 x 2)-O domains on the Cu(100) surface. PMID- 9986068 TI - Controlled lateral and perpendicular motion of atoms on metal surfaces. PMID- 9986069 TI - Ultrathin films of cobalt on Fe{001} and the effect of oxygen. PMID- 9986070 TI - Electronic properties and magnetism of ruthenium clusters. PMID- 9986071 TI - Optical and structural properties of oligothiophene crystalline films. PMID- 9986072 TI - Atom-surface scattering under classical conditions. PMID- 9986073 TI - Surface structure and doping-induced etching of Si(100) by chlorine: First principles study. PMID- 9986074 TI - Molecular-dynamics studies of defect generation in epitaxial Mo/W superlattices. PMID- 9986075 TI - Theory of the scanning tunneling microscope: Xe on Ni and Al. PMID- 9986076 TI - Bulk and surface electronic structure of Li2O. PMID- 9986078 TI - Temperature-dependent scanning tunneling spectroscopy of 1T-TaS2. PMID- 9986077 TI - Structure and stability of TinNm clusters. PMID- 9986079 TI - Interaction of oxygen with silver at high temperature and atmospheric pressure: A spectroscopic and structural analysis of a strongly bound surface species. PMID- 9986081 TI - Onsager relations and hydrodynamic balance equations. PMID- 9986080 TI - Erratum: Electron in a magnetic field interacting with point impurities PMID- 9986082 TI - Energy-loss function in the two-pair approximation for the electron liquid. PMID- 9986083 TI - Lowest-order corrections to the RPA polarizability and GW self-energy of a semiconducting wire. PMID- 9986084 TI - Ab initio investigation of the electronic properties of planar and twisted polyparaphenylenes. PMID- 9986085 TI - Subgap optical absorption induced by quantum lattice fluctuations at the Peierls edge in PtCl chain complexes. PMID- 9986087 TI - Spin-gap phase in nearly half-filled one-dimensional conductors coupled with phonons. PMID- 9986086 TI - Theoretical and experimental study of positron annihilation with core electrons in solids. PMID- 9986088 TI - Semiempirical Hartree-Fock calculations for KNbO3. PMID- 9986089 TI - Color of pure and alkali-doped cerium sulfide: A local-density-functional study. PMID- 9986090 TI - Electronic structure and optical properties of WO3, LiWO3, NaWO3, and HWO3. PMID- 9986091 TI - Calculated optical properties of thorium, protactinium, and uranium metals. PMID- 9986093 TI - Nonlinear Berry phases for simple band representations. PMID- 9986092 TI - Complete band-structure determination of the quasi-two-dimensional Fermi-liquid reference compound TiTe2. PMID- 9986094 TI - Collective modes of the one-dimensional Fermi gas within the quasiparticle random phase approximation. PMID- 9986095 TI - Calculated optical properties of Si, Ge, and GaAs under hydrostatic pressure. PMID- 9986096 TI - k PMID- 9986098 TI - Evaluation of some basic positron-related characteristics of SiC. PMID- 9986097 TI - Electronic structure and hyperfine interactions for deep donors and vacancies in II-VI compound semiconductors. PMID- 9986099 TI - Free exciton emission in GaN. PMID- 9986100 TI - Nonmonotonic decay of nonequilibrium polariton condensate in direct-gap semiconductors. PMID- 9986102 TI - Experimental evidence for luminescence from silicon oxide layers in oxidized porous silicon. PMID- 9986101 TI - Optically active erbium centers in silicon. PMID- 9986103 TI - Cohesive energies of cubic III-V semiconductors. PMID- 9986105 TI - Complete theoretical analysis of the Kaplan-Solomon-Mott mechanism of spin dependent recombination in semiconductors. PMID- 9986104 TI - Phonon-induced dephasing of localized optical excitations. PMID- 9986106 TI - Localization and delocalization of electrons in narrow-band semiconductors under the action of strong time-dependent and constant electric fields. PMID- 9986107 TI - Self-diffusion on Si(111) surfaces. PMID- 9986108 TI - Electronic properties of Sb deposited on GaAs(110) in the submonolayer coverage regime. PMID- 9986110 TI - Quantum scars of classical orbits in small interacting electronic systems. PMID- 9986109 TI - Quantum conductance of carbon nanotubes with defects. PMID- 9986112 TI - Quantum transport through a periodic scatterer in a magnetic field. PMID- 9986111 TI - Recombination dynamics of localized excitons in a CdSe/ZnSe/ZnSxSe1-x single quantum-well structure. PMID- 9986113 TI - Low-temperature atomic dynamics of the Si(111)-7 x 7. PMID- 9986114 TI - Plasmon excitations and accumulation layers in heavily doped InAs(001). PMID- 9986115 TI - Hole confinement in boron delta -doped silicon quantum wells studied by deep level transient spectroscopy. PMID- 9986116 TI - Bound and resonant electron states in quantum dots: The optical spectrum. PMID- 9986117 TI - Energy subbands, envelope states, and intersubband optical transitions in one dimensional quantum wires: The local-envelope-states approach. PMID- 9986118 TI - Temperature dependence of the magnetoresistance of InxGa1-xAs antidot lattices. PMID- 9986119 TI - Elastic- and inelastic-scattering effects on electron magnetotunneling through a quantum well. PMID- 9986120 TI - Universal correlations of Coulomb-blockade conductance peaks and the rotation scaling in quantum dots. PMID- 9986121 TI - Specific heat and validity of the quasiparticle approximation in the half-filled Landau level. PMID- 9986123 TI - Topological disorder and conductance fluctuations in thin films. PMID- 9986122 TI - Interface properties and valence-band discontinuity of MnS/ZnSe heterostructures. PMID- 9986124 TI - Superlattice effects induced by atomic ordering on GaxIn1-xP Raman modes. PMID- 9986125 TI - Exciton localization, photoluminescence spectra, and interface roughness in thin quantum wells. PMID- 9986127 TI - Energy relaxation of an excited electron gas in quantum wires: Many-body electron LO-phonon coupling. PMID- 9986126 TI - Theoretical investigation of excitonic surface states in multilayer organic quantum wells: Radiative decay rates of the first and second surface excitons. PMID- 9986129 TI - Effect of exciton-carrier thermodynamics on the GaAs quantum well photoluminescence. PMID- 9986128 TI - Optical observation of impurity localized states at the edges of Landau subbands in doped quantum wells. PMID- 9986130 TI - Emission of acoustic and optical phonons by hot electrons in a two-dimensional electron system in parallel magnetic fields. PMID- 9986131 TI - Dynamic dielectric properties of a bounded solid-state plasma and a two dimensional electron sheet: Inverse dielectric function and coupled collective modes. PMID- 9986132 TI - Scattering of plasmons in a quasi-two-dimensional electron gas containing a fixed point charge. PMID- 9986133 TI - Mesoscopic charge-density-wave junctions. PMID- 9986134 TI - Reflection of finite-width edge channels. PMID- 9986135 TI - Investigation of deep metastable traps in Si delta -doped GaAs/Al0.33Ga0.67As quantum-well samples using noise spectroscopy. PMID- 9986137 TI - X-ray absorption at the L2,3 edge of an anisotropic single crystal: Cadmium (0001). PMID- 9986136 TI - Structure of Mn films grown on (111) and (001) fcc Ir determined by EXAFS and the multiple-scattering approach. PMID- 9986138 TI - Structural determination of the Pd{110}(2 x 1)p2mg-CO system by means of high energy x-ray photoelectron diffraction. PMID- 9986140 TI - Atomic structure of amorphous nanosized silicon powders upon thermal treatment. PMID- 9986139 TI - Measurement of roughness at buried Si/SiO2 interfaces by transmission electron diffraction. PMID- 9986141 TI - Vibrational signatures for low-energy intermediate-sized Si clusters. PMID- 9986142 TI - Theoretical study of O adlayers on Ru(0001). PMID- 9986143 TI - Electronic and geometric structure of NH3 on Ge(001) under equilibrium adsorption conditions. PMID- 9986145 TI - First-order orientational-disordering transition on the (111) surface of C60. PMID- 9986144 TI - Self-diffusion on low-index metallic surfaces: Ag and Au (100) and (111). PMID- 9986146 TI - Electronic specific heat of single-walled carbon nanotubes. PMID- 9986148 TI - Oscillatory interaction of steps on W{110} PMID- 9986147 TI - Electron-energy losses in hemispherical targets. PMID- 9986149 TI - Determination of the electronic density of states near buried interfaces: Application to Co/Cu multilayers. PMID- 9986151 TI - Kinetics of nucleation-dominated step flow. PMID- 9986150 TI - Magnetic dichroism in valence-band photoemission from Co/Cu(001): Experiment and theory. PMID- 9986152 TI - Stability of NanPb (n <~ 7) clusters: A first-principles molecular-dynamics study. PMID- 9986154 TI - Surface polaritons in layered structures of anisotropic media. PMID- 9986153 TI - Computer simulation of the ground-state atomic configurations of Ni-Al clusters using the embedded-atom model. PMID- 9986155 TI - Stability and charge transfer of C3B ordered structures. PMID- 9986156 TI - Multiconfigurational symmetrized-projector quantum Monte Carlo method for low lying excited states of the Hubbard model. PMID- 9986157 TI - Electron focusing in Ag and W single crystals. PMID- 9986159 TI - Localization of a disordered phonon system: Anderson localization of optical phonons in AlxGa1-xAs. PMID- 9986158 TI - Virtual states and photon-assisted tunneling. PMID- 9986160 TI - Weak localization of exciton polaritons in a quantum well. PMID- 9986161 TI - Long-lived charged multiple-exciton complexes in strong magnetic fields. PMID- 9986162 TI - Electronic structure of InAs/GaAs self-assembled quantum dots. PMID- 9986163 TI - Evidence of spontaneous formation of steps on silicon (100). PMID- 9986164 TI - Interchain photoluminescence in poly(phenylene vinylene) derivatives. PMID- 9986165 TI - Flux-periodic resistance oscillations in arrays of superconducting weak links based on InAs-AlSb quantum wells with Nb electrodes. PMID- 9986166 TI - Magnetic-field-induced resonant tunneling in parallel two-dimensional systems. PMID- 9986167 TI - Magnetotransport and interlayer-edge channel tunneling of two-dimensional electrons in a double-quantum-well system. PMID- 9986169 TI - Experimental indication for supercurrents carried by opened transport channels. PMID- 9986170 TI - Many-Skyrmion wave functions and Skyrmion statistics in quantum Hall ferromagnets. PMID- 9986168 TI - Electric-field domain formation in type-II superlattices. PMID- 9986172 TI - Spherosiloxane H8Si8O12 clusters on Si(001): First-principles calculation of Si 2p core-level shifts. PMID- 9986171 TI - Dielectric enhancement of excitons in near-surface quantum wells. PMID- 9986174 TI - Incorporation of alkali metals on Pt(111). PMID- 9986173 TI - Effect of interface magnetic moments and quantum-well states on magnetization induced second-harmonic generation. PMID- 9986175 TI - Numerical study of excitons in a two-dimensional organic dye aggregate. PMID- 9986176 TI - Fractal dimension of Li insertion electrodes studied by diffusion-controlled voltammetry and impedance spectroscopy. PMID- 9986177 TI - Finite-size effects on the incommensurate phase transition of bis(4 chlorophenyl)sulphone studied by 35Cl NQR. PMID- 9986178 TI - Effects of higher-coordination shells in garnets detected by x-ray-absorption spectroscopy at the Al K edge. PMID- 9986179 TI - Computer-simulation study of the thermal conductivity of amorphous insulating solids. PMID- 9986180 TI - Fluctuating loops and glassy dynamics of a pinned line in two dimensions. PMID- 9986181 TI - Theory of inelastic x-ray scattering by phonons in ice. PMID- 9986182 TI - Effects of quantum lattice fluctuations on vibron pairing in two-site systems. PMID- 9986183 TI - Hyperuniversal amplitude ratios and the central charge of the spin-one Ising model. PMID- 9986185 TI - Tight-binding study of the ionization of iron clusters. PMID- 9986184 TI - Replica symmetry breaking for a simple model of a quadrupolar glass. PMID- 9986186 TI - Charge ordering and magnetoresistance in Nd1-xCaxMnO3 due to reduced double exchange. PMID- 9986188 TI - Competition between spin, charge, and bond waves in a Peierls-Hubbard model. PMID- 9986187 TI - Influence of side groups on 90 degrees superexchange: A modification of the Goodenough-Kanamori-Anderson rules. PMID- 9986190 TI - Series expansion for the J1-J2 Heisenberg antiferromagnet on a square lattice. PMID- 9986189 TI - Monte Carlo calculation of the transition temperature of the anisotropic three dimensional XY model. PMID- 9986191 TI - Tensile stress dependence of the Curie temperature and hyperfine field in Fe-Zr-B (Cu) amorphous alloys. PMID- 9986193 TI - Giant magnetoresistance in Cu-Mn-Al. PMID- 9986192 TI - Structural, magnetic, and electronic properties of Fe/Au monatomic multilayers. PMID- 9986194 TI - NMR studies of Na atoms in silicon clathrate compounds. PMID- 9986195 TI - Renormalization-group approach to Fermi-liquid theory. PMID- 9986196 TI - Relaxation of charge imbalance in a d-wave superconductor. PMID- 9986198 TI - First-order vortex unbinding transition in thin superconducting films. PMID- 9986197 TI - Radiation linewidth of a long Josephson junction in the flux-flow regime. PMID- 9986199 TI - Conspicuous domination of polarization relaxation in kinetics of first-order phase transitions in perovskites. PMID- 9986200 TI - Superconductivity in a strongly correlated one-band system. PMID- 9986201 TI - Thermal conductivity of RNi2B2C (R=Y,Ho) single crystals. PMID- 9986202 TI - Effect of pressure on spin-gap behavior in Pr-doped and oxygen-deficient YBa2Cu3O7 thin films. PMID- 9986204 TI - First-principles determination of the effects of boron and sulfur on the ideal cleavage fracture in Ni3Al. PMID- 9986203 TI - Spin-gap behavior in underdoped TlSr2(Lu0.7Ca0.3)Cu2Oy: 63Cu and 205Tl NMR studies. PMID- 9986205 TI - Hydrogen-induced lattice expansion in a (001)-oriented Mo/V superlattice. PMID- 9986207 TI - Thermal conductivity of C60 at pressures up to 1 GPa and temperatures in the 50 300 K range. PMID- 9986206 TI - Positron studies of defects in ion-implanted SiC. PMID- 9986208 TI - Evaluation of time-dependent grain-size populations for nucleation and growth kinetics. PMID- 9986209 TI - Time dependence of dislocation arrays in ice during recrystallization. PMID- 9986211 TI - Optical activity in the incommensurate phase of ((CH3)4N)2ZnCl4. PMID- 9986210 TI - Synchrotron x-ray-scattering study of the normal-incommensurate phase transition in Rb2ZnCl4. PMID- 9986213 TI - Evolution of long-range order and composition for radiation-induced precipitate dissolution. PMID- 9986212 TI - Influence of incommensurate modulation on the optical properties of the solid solution ((CH3)4N)2ZnCl2.8Br1.2. PMID- 9986214 TI - Phase transitions and glasslike behavior in Sr1-xBaxTiO3. PMID- 9986215 TI - Grain-size effect on structure and phase transformations for barium titanate. PMID- 9986216 TI - Improved R-space resolution of EXAFS spectra using combined regularization methods and nonlinear least-squares fitting. PMID- 9986217 TI - Low-mass secondary-ion ejection from molecular solids by MeV heavy ions: Radial velocity distributions. PMID- 9986219 TI - Experimental studies of atomic structure, electronic structure, and the electronic transport mechanism in amorphous Al-Cu-Y and Mg-Cu-Y ternary alloys. PMID- 9986218 TI - Self-consistent mean-field theory of asymmetric first-order structural phase transitions. PMID- 9986220 TI - Local atomic order and individual pair displacements of Fe46.5Ni53.5 and Fe22.5Ni77.5 from diffuse x-ray scattering studies. PMID- 9986221 TI - Kinetic features of phase separation under alloy ordering. PMID- 9986222 TI - Sharpening of enhanced backscattering peak in a disordered gain medium. PMID- 9986224 TI - Modulation instability and recurrence phenomena in anharmonic lattices. PMID- 9986223 TI - Measurements of the ballistic-phonon component resulting from nuclear and electron recoils in crystalline silicon. PMID- 9986225 TI - Molecular dynamics and higher-order perturbation-theory results for the anharmonic free energy and equation of state of a Lennard-Jones solid. PMID- 9986227 TI - Stochastic approach to simulation of lattice vibrations in strongly anharmonic crystals: Anomalous frequency dependence of the dynamic structure factor. PMID- 9986226 TI - Nonadiabatic effects in a soliton ground state of an extended Jahn-Teller system in one dimension. PMID- 9986229 TI - Memory effects in the frictional damping of diffusive and vibrational motion of adatoms. PMID- 9986228 TI - Giant enhancement of cubic nonlinearity in a polycrystalline quasi-one dimensional conductor. PMID- 9986230 TI - Spin diffusion in one-dimensional antiferromagnets. PMID- 9986232 TI - Griffiths singularities in the disordered phase of a quantum Ising spin glass. PMID- 9986231 TI - Tunneling theory for exchange coupling between two ferromagnets separated by an amorphous-semiconducting barrier. PMID- 9986234 TI - Quantum fluctuations in a disordered two-dimensional spin model. PMID- 9986233 TI - Quantum Griffiths singularities in the transverse-field Ising spin glass. PMID- 9986235 TI - Vortex statistics in a disordered two-dimensional XY model. PMID- 9986236 TI - Quantum orientational glasses: Large-M limit approach. PMID- 9986237 TI - Magnetically induced crystal structure and phase stability in Fe1-cCoc. PMID- 9986238 TI - Brillouin light scattering study of Fe/Cr/Fe (211) and (100) trilayers. PMID- 9986239 TI - Phase diagram for the striped phase in the two-dimensional dipolar Ising model. PMID- 9986240 TI - Surface-induced superparamagnetic relaxation in nanoscale ferrihydrite particles. PMID- 9986241 TI - Magnetic properties and magnetic phase diagram of the frustrated Co1-xFexPt3 compounds. PMID- 9986243 TI - Nanoscale magnetic domain structures in epitaxial cobalt films. PMID- 9986242 TI - Magnetic order in the random-field Ising film Fe0.52Zn0.48F2. PMID- 9986244 TI - Universality of the Ising model on spherelike lattices. PMID- 9986245 TI - Critical behavior of weakly disordered anisotropic systems in two dimensions. PMID- 9986247 TI - Experimental study of ferromagnetic chains composed of nanosize Fe spheres. PMID- 9986246 TI - Electronic transport and Kondo effect in La1-xCex films. PMID- 9986248 TI - Raman scattering in a two-layer antiferromagnet. PMID- 9986250 TI - Superconducting order parameters with sign changes: The density of states and impurity scattering. PMID- 9986249 TI - London penetration depth of strongly coupled isotropic superconductors: Low temperature behavior. PMID- 9986252 TI - Critical statistical charge for anyonic superconductivity. PMID- 9986251 TI - Quasiparticle band in the frustrated t-t'-J model. PMID- 9986253 TI - Kinetics of vortex formation in superconductors with d pairing. PMID- 9986255 TI - Flux penetration into flat superconductors of arbitrary shape: Patterns of magnetic and electric fields and current. PMID- 9986254 TI - Complex conductivity of proximity-superconducting Nb/Cu bilayers. PMID- 9986256 TI - Robust critical behavior in YBa2Cu3O7 thin films. PMID- 9986257 TI - Screening effect of Ohmic and superconducting planar thin films. PMID- 9986258 TI - Fast algorithms for Josephson-junction arrays: Busbars and defects. PMID- 9986260 TI - 63/65Cu/203/205Tl NMR study on the antiferromagnetic phase of the Tl-based high Tc oxide TlBa2YCu2O7. PMID- 9986259 TI - Eliashberg-type equations for correlated superconductors. PMID- 9986261 TI - Photovoltaic effect in small superconducting-normal-metal systems. PMID- 9986263 TI - Ion-size effect on transport properties in R0.9Ca0.1Ba2Cu3O7- delta systems (R=Tm, Ho, Gd, and Nd). PMID- 9986262 TI - Inverse photoemission in strongly correlated electron systems. PMID- 9986264 TI - Charge-transfer model of s- and d-wave pairing in the cuprates. PMID- 9986265 TI - Anomalous behavior of a Fermi system interacting with a bosonic critical mode. PMID- 9986266 TI - Transport properties of high-Tc Bi2Sr2CaCu2O8+ delta crystals near the superconducting transition. PMID- 9986267 TI - Magnetoresistivity of thin films of the electron-doped high-Tc superconductor Nd1.85Ce0.15CuO4+/- delta. PMID- 9986268 TI - Theory of tunneling and photoemission spectroscopy for high-temperature superconductors. PMID- 9986269 TI - Interaction of two-dimensional vortices with linear ion tracks in the highly anisotropic layered cuprates. PMID- 9986270 TI - c-axis resistance peak above the critical temperature in layered superconductors. PMID- 9986272 TI - Tunneling in two-channel Kondo superconducting junctions. PMID- 9986271 TI - Pinning phenomena and critical current in proton-irradiated sintered YBa2Cu3O7- delta. PMID- 9986274 TI - Theory of superconducting Tc of doped fullerenes. PMID- 9986273 TI - Effect of van Hove singularities on a spin liquid. PMID- 9986275 TI - Erratum: Optical alignment of axial Fe centers in KTaO3 PMID- 9986277 TI - Disorder effects of nitrogen impurities, irradiation-induced defects, and 13C isotope composition on the Raman spectrum in synthetic Ib diamond. PMID- 9986276 TI - Erratum: Electric-field-dependent variable-range hopping conductance in quasi-two dimensional systems: Application to PrBa2Cu3O7-y-based superconductor-normal metal-superconductor junctions PMID- 9986278 TI - Electron-irradiation- and ion-beam-induced amorphization of coesite. PMID- 9986279 TI - High-pressure densification of silica glass: A molecular-dynamics simulation. PMID- 9986280 TI - First-principles study of stability and vibrational properties of tetragonal PbTiO3. PMID- 9986281 TI - Cross-relaxation process between +3 rare-earth ions in LiYF4 crystals. PMID- 9986282 TI - Optical absorption and luminescence spectroscopy of U3+ in K2LaX5 (X=Cl,Br,I). PMID- 9986283 TI - Stability criteria for homogeneously stressed materials and the calculation of elastic constants. PMID- 9986285 TI - Dynamical diffraction in electron-energy-loss spectrometry: The independent Bloch wave model. PMID- 9986284 TI - Tricritical Lifshitz point in uniaxial ferroelectrics. PMID- 9986286 TI - Isotope-induced energy-spectrum renormalization of the Wannier-Mott exciton in LiH crystals. PMID- 9986287 TI - Changes in the voltage profile of Li/Li1+xMn2-xO4 cells as a function of x. PMID- 9986288 TI - Magnetic excitation spectra and thermodynamics of amorphous PrNi5. PMID- 9986290 TI - Percolation transition in conducting polymer networks. PMID- 9986289 TI - Structure determination of Ag-Ge-S glasses using neutron diffraction. PMID- 9986291 TI - Electromagnetic localization in one-dimensional stacks with random loss and gain. PMID- 9986293 TI - Fluctuation theory of relaxation phenomena in disordered conductors: How fitting laws such as those of Kohlrausch and Jonscher are obtained from a consistent approach. PMID- 9986292 TI - T-matrix approach to effective nonlinear elastic constants of heterogeneous materials. PMID- 9986294 TI - Mean-field theory of strongly nonlinear random composites: Strong power-law nonlinearity and scaling behavior. PMID- 9986296 TI - Magnetoabsorption of large bipolarons. PMID- 9986295 TI - Bond-stability criterion in chain dynamics. PMID- 9986298 TI - Vibronic intensities in the absorption spectra of Yb3+ PMID- 9986297 TI - Raman scattering in calcium-doped C60. PMID- 9986299 TI - Brillouin and Raman scattering in natural and isotopically controlled diamond. PMID- 9986301 TI - Calculation of the recoilless gamma -ray emission spectra from a substitutional cation impurity diffusing via the <001> channels in the rutile structure. PMID- 9986300 TI - Random walk in the Cu/graphite mixtures. PMID- 9986302 TI - Theory of commensurable magnetic structures in holmium. PMID- 9986303 TI - Thermodynamics of the Ishimori-Haldane-Faddeev ferromagnetic chain: The field dependent case. PMID- 9986304 TI - S=2 antiferromagnetic quantum spin chain. PMID- 9986306 TI - Ferromagnetism in multiband Hubbard models: From weak to strong Coulomb repulsion. PMID- 9986305 TI - Pseudofermion method applied to the high-local-spin system. PMID- 9986307 TI - Compton scattering study of 4f magnetism in CeFe2. PMID- 9986308 TI - Structural relaxation and magnetic anisotropy in Co/Cu(001) films. PMID- 9986309 TI - Effect of S segregation on the surface magnetism of Fe(100). PMID- 9986310 TI - Effect of spin-system fluctuations on heat transport in RbMnF3 close to the Neel temperature. PMID- 9986311 TI - ac susceptibility of a DyFe11Ti single crystal. PMID- 9986312 TI - Magnetic properties, relaxation, and quantum tunneling in CoFe2O4 nanoparticles embedded in potassium silicate. PMID- 9986313 TI - Effect of Co substitution for Fe on magnetic and magnetostrictive properties in Sm0.88Dy0.12(Fe1-xCox)2 compounds. PMID- 9986314 TI - Analytical and computational study of magnetization switching in kinetic Ising systems with demagnetizing fields. PMID- 9986316 TI - Reorientation transitions in ultrathin ferromagnetic films by thickness- and temperature-driven anisotropy flows. PMID- 9986315 TI - Magnetization reversal dynamics in ultrathin magnetic layers. PMID- 9986317 TI - Magnetic and melting transitions of oxygen monolayers and multilayers physisorped on exfoliated graphite. PMID- 9986318 TI - fcc Fe films grown on a ferromagnetic fcc Co(100) substrate. PMID- 9986319 TI - Influence of exchange-coupled anisotropies on spin-wave frequencies in magnetic layered systems: Application to Co/CoO. PMID- 9986320 TI - Phase diagram of XY antiferromagnetic stacked triangular lattices. PMID- 9986321 TI - Closure of the Monte Carlo dynamical equations in the spherical Sherrington Kirkpatrick model. PMID- 9986322 TI - Phase diagram of disordered boson systems in the presence of random hopping. PMID- 9986323 TI - Thermal expansion of CePdSb near the ferromagnetic transition. PMID- 9986324 TI - Two-dimensional electrons in random magnetic fields: Universality class of random matrices. PMID- 9986325 TI - Gaussian-approximation formalism for evaluating decay of NMR spin echoes. PMID- 9986326 TI - Parquet-graph resummation method for vortex liquids. PMID- 9986327 TI - Temperature dependence of the low-field magnetization of granular superconductors. PMID- 9986329 TI - Superconductors of finite thickness in a perpendicular magnetic field: Strips and slabs. PMID- 9986328 TI - Absence of persistent magnetic oscillations in type-II superconductors. PMID- 9986330 TI - Pressure dependence of the superconducting critical temperature of HgBa2Ca2Cu3O8+y and HgBa2Ca3Cu4O10+y up to 30 GPa. PMID- 9986331 TI - Raman study of intermultiplet crystal-field transitions in Sm2CuO4. PMID- 9986332 TI - Size effects in the density of states in normal-metal-superconductor and superconductor-normal-metal-superconductor junctions. PMID- 9986333 TI - Electron-electron interaction and normal-state transport in superconducting Ti (Sn,Ge) alloys. PMID- 9986334 TI - Bosonization of the two-dimensional t-J model in the continuum limit. PMID- 9986335 TI - Desorption of oxygen from YBa2Cu3O6+x films studied by Raman spectroscopy. PMID- 9986336 TI - Stripe structure of the CuO2 plane in Bi2Sr2CaCu2O8+y by anomalous x-ray diffraction. PMID- 9986337 TI - Monte Carlo investigation of the role of initial conditions on oxygen diffusion in planar YBa2Cu3O6+c. PMID- 9986338 TI - Plane-chain coupling in YBa2Cu3O7: Impurity effect on the critical temperature. PMID- 9986339 TI - Anisotropic order parameters with s- and d-wave-like symmetry and the transition temperature in high-Tc layered superconductors. PMID- 9986341 TI - In-plane paraconductivity and fluctuation-induced magnetoconductivity in biperiodic layered superconductors: Application to YBa2Cu3O7- delta. PMID- 9986340 TI - Theory for dynamical short-range order and Fermi surface volume in strongly correlated systems. PMID- 9986343 TI - High-pressure structural phases of titanium dioxide. PMID- 9986342 TI - Dynamics of oxygen ordering in the cell-doubled phase of YBa2Cu3O6+x. PMID- 9986344 TI - High-resolution 13C NMR studies of high-pressure-polymerized C60: Evidence for the PMID- 9986345 TI - Structural phase transition and Tc distribution in Hf-doped LaMnO3 investigated using perturbed-angular-correlation spectroscopy. PMID- 9986346 TI - Spatially and temporally resolved emission from aggregates in conjugated polymers. PMID- 9986347 TI - Uncertainty relation in fluctuations in the space and time domains in disordered optical media. PMID- 9986348 TI - Spectral hole burning in Eu3+-doped highly porous gamma -aluminum oxide. PMID- 9986350 TI - Scaling above the upper critical dimension in Ising models. PMID- 9986349 TI - Experimental evidence for the dynamic Jahn-Teller effect in La0.65Ca0.35MnO3. PMID- 9986351 TI - Observation of internal interfaces in PtxCo1-x (x PMID- 9986353 TI - Magnetoresistance anomalies and multiple magnetic transitions in SmMn2Ge2. PMID- 9986352 TI - Theory of the anomalous magnetic phase transition in UNiSn. PMID- 9986354 TI - Susceptibility and low-temperature thermodynamics of spin-1/2 Heisenberg ladders. PMID- 9986355 TI - Photoemission spectra in t-J ladders with two legs. PMID- 9986356 TI - Observation of an antiferromagnetic resonance in the spin-Peierls compound CuGeO3 doped with Zn. PMID- 9986357 TI - Itinerant antiferromagnetism in the Mott compound V1.973O3. PMID- 9986359 TI - Quasimagnetic ordering of planar spins in a random anisotropy system: Dy(As0.35V0.65)O4. PMID- 9986358 TI - Dynamics in the dimerized and the high-field incommensurate phase of CuGeO3. PMID- 9986360 TI - Interlayer magnetic coupling: Effect of alloying in the spacer. PMID- 9986361 TI - Perovskite oxide superlattices: Magnetotransport and magnetic properties. PMID- 9986362 TI - Phase separation and the existence of superconductivity in a one-dimensional copper-oxygen model. PMID- 9986363 TI - Enhancement of persistent photoconductivity by uv excitation in GdBa2Cu3O6.3. PMID- 9986364 TI - Power-law dependence of the ab-plane penetration depth in Nd1.85Ce0.15CuO4-y. PMID- 9986365 TI - Superconductor-insulator transition in a disordered electronic system. PMID- 9986367 TI - ESR evidence for phonon-mediated resistivity in alkali-metal-doped fullerides. PMID- 9986366 TI - Anomalous magnetization and dimensional crossover of the vortex system in the organic superconductor kappa -(BEDT-TTF)2Cu(NCS)2. PMID- 9986368 TI - Vortex dynamics in Rb3C60 observed by 87Rb and 13C NMR. PMID- 9986369 TI - Heavy-electron behavior in single-crystal YbNi2B2C. PMID- 9986370 TI - Resistivity of single- and multiple-domain thin films of PrBa2Cu3O7 from 0.05 to 500 K. PMID- 9986371 TI - Excitons in insulating cuprates. PMID- 9986372 TI - Paramagnetic ac susceptibility at the first-order vortex-lattice phase transition. PMID- 9986373 TI - Specific heat of low-Tc Tl2Ba2CuO6+ delta. PMID- 9986374 TI - Finite-temperature mobility of a particle coupled to a fermionic environment. PMID- 9986375 TI - Umklapp processes for electrons and their renormalization-group flow. PMID- 9986377 TI - Charge-ordered insulating state of Fe3O4 from first-principles electronic structure calculations. PMID- 9986376 TI - Towards a potential-based conjugate gradient algorithm for order-N self consistent total energy calculations. PMID- 9986378 TI - Electronic states of Cu in cuprate superconductors: Atomic model. PMID- 9986379 TI - Boltzmann-Green functions for nonequilibrium fluctuations in metallic systems. PMID- 9986380 TI - Applications of reflection positivity in strongly correlated electron systems. PMID- 9986381 TI - X-ray-absorption problem in metals within the one-electron approximation: Extension to finite temperature. PMID- 9986382 TI - Low-energy d-d excitations in MnO studied by resonant x-ray fluorescence spectroscopy. PMID- 9986383 TI - Line shape of the no-phonon luminescence of excitons bound to phosphorus in carbon-doped silicon. PMID- 9986385 TI - Model for the photoluminescence behavior of porous silicon. PMID- 9986384 TI - Evidence concerning the effect of topology on electrical switching in chalcogenide network glasses. PMID- 9986386 TI - Bloch oscillations in In-Ga-As-P/In-Ga-As-P heterostructures observed with time resolved transmission spectroscopy. PMID- 9986387 TI - Structure and surface kinetics of bismuth adsorption on Si(001). PMID- 9986388 TI - Electronic properties of monolayer steps on (2 x 4)/c(2 x 8) reconstructed GaAs(001) surfaces. PMID- 9986389 TI - Surface kinetics of zinc-blende (001) GaN. PMID- 9986391 TI - Wigner-function approach to a single-electron tunnel junction. PMID- 9986392 TI - Conductance increase by electron-phonon interaction in quantum wires. PMID- 9986390 TI - Disorder mediated biexcitonic beats in semiconductor quantum wells. PMID- 9986394 TI - Observability of the magnetic band structure of lateral superlattices. PMID- 9986393 TI - Effect of interedge Coulomb interactions on the transport between quantum Hall edge states. PMID- 9986395 TI - Surface core levels of In adsorption on Si(001)2 x 1. PMID- 9986396 TI - Intensity-dependent electroabsorption line shape in Cd(S,Se) quantum dots. PMID- 9986397 TI - Quasiperiodic magnetoresistance oscillations in narrow quasiballistic wire in the quantum Hall regime. PMID- 9986398 TI - Fermion Chern-Simons gauge theory of the fractional quantum Hall effect for electromagnetic polarization tensor. PMID- 9986400 TI - Surface core-level shift of InSb(111)-2 x 2. PMID- 9986399 TI - Electroluminescence spectroscopy of intervalley scattering and hot-hole transport in a GaAs/AlxGa1-xAs tunneling structure. PMID- 9986401 TI - RbF/Ge(111) interface formation studied by LEED, XPS, and UPS. PMID- 9986403 TI - Observation of laser-induced microscale knotted and unknotted vortex filaments on vaporizing tantalum surface. PMID- 9986402 TI - Time-dependent local-density approximation in real time. PMID- 9986404 TI - Size dependence of force between parallel planar jellium metal surfaces at small separation. PMID- 9986405 TI - Intermixing during growth of Cr on Fe(100) studied by proton- and electron induced Auger-electron spectroscopy. PMID- 9986406 TI - Scanning-tunneling-microscopy observation of stress-driven surface diffusion due to localized strain fields of misfit dislocations in heteroepitaxy. PMID- 9986408 TI - Monte Carlo study of electron transmission and backscattering from metallic thin films. PMID- 9986407 TI - Excitonic spectra of solid C60. PMID- 9986410 TI - Anomalous branching ratio of the Cs 4d doublet in submonolayer depositions. PMID- 9986409 TI - Dependence of implanted K+ cluster formation on the shift of the W work function. PMID- 9986411 TI - Applications of a tight-binding total-energy method for transition and noble metals: Elastic constants, vacancies, and surfaces of monatomic metals. PMID- 9986413 TI - Fermi-edge singularity in one-dimensional electron systems with long-range Coulomb interactions. PMID- 9986412 TI - Accurate evaluation of the interstitial KKR Green function. PMID- 9986415 TI - Influence of lattice effects on the electron-positron interaction in metals. PMID- 9986414 TI - Critical behavior at the metal-insulator transition in three-dimensional disordered systems in a strong magnetic field. PMID- 9986416 TI - Magnetotransport and thermopower properties of the quasi-two-dimensional charge density-wave compounds (PO2)4 (WO3)2m (m=4,6). PMID- 9986417 TI - Energy-transfer processes between Tm3+ and Pr3+ Ions in CsCdBr3. PMID- 9986418 TI - Calculation of core-hole excitonic features on Al L23-edge x-ray-absorption spectra of alpha -Al2O3. PMID- 9986419 TI - Nonlinear optical response of conjugated polymers: Essential excitations and scattering. PMID- 9986421 TI - Dissipative quantum tunneling of a single defect in a disordered metal. PMID- 9986420 TI - Mid-infrared properties of a VO2 film near the metal-insulator transition. PMID- 9986423 TI - Clustering process of interstitial atoms in gallium phosphide studied by transmission electron microscopy. PMID- 9986422 TI - Molecular-dynamics study on atomistic structures of liquid silicon. PMID- 9986424 TI - Tight-binding models for compounds: Application to SiC. PMID- 9986425 TI - Coupled free-carrier and exciton relaxation in optically excited semiconductors. PMID- 9986426 TI - High-field mobility in an assembly of conjugated polymer segments. PMID- 9986428 TI - Anti-Stokes luminescence in chromium-doped ZnSe. PMID- 9986427 TI - Ground-state properties of isolated interstitial iron in silicon: Electronic structure and hyperfine interactions. PMID- 9986429 TI - Homogeneous linewidth of bound excitons in high-purity GaAs measured by spectral hole burning. PMID- 9986430 TI - Anharmonic effects in light scattering due to optical phonons in CuGaS2. PMID- 9986431 TI - Spectroscopy of donor-acceptor pairs in nitrogen-doped ZnSe. PMID- 9986432 TI - Defect identification using the core-electron contribution in Doppler-broadening spectroscopy of positron-annihilation radiation. PMID- 9986433 TI - Dependence of the lattice parameters and the energy gap of zinc-blende-type semiconductors on isotopic masses. PMID- 9986435 TI - Mechanism of carrier generation in poly(phenylene vinylene): Transient photoconductivity and photoluminescence at high electric fields. PMID- 9986434 TI - Ab initio pseudopotential calculations of B diffusion and pairing in Si. PMID- 9986436 TI - Measurement of diffusion and drift of charge carriers from photocurrent transients. PMID- 9986437 TI - Direct observation of ordered trimers on Si(111) sqrt 3 x sqrt 3 R30 degrees-Au by scanned-energy glancing-angle Kikuchi electron wave-front reconstruction. PMID- 9986438 TI - Reconstruction of the Si(113) surface. PMID- 9986439 TI - Photoinduced electron coupling in delta -doped GaAs/In0.18Ga0.82As quantum wells. PMID- 9986441 TI - Optical properties of two interacting electrons in quantum rings: Optical absorption and inelastic light scattering. PMID- 9986440 TI - Fixed-phase quantum Monte Carlo method applied to interacting electrons in a quantum dot. PMID- 9986442 TI - Ground-state energy of an exciton in a quantum-dot superlattice grown on a terraced substrate. PMID- 9986443 TI - Magneto-optical properties of diluted magnetic PbSe/Pb1-xMnxSe superlattices. PMID- 9986444 TI - Relationship between nonparabolicity and confinement energies in In0.53Ga0.47As/InP quantum wires. PMID- 9986445 TI - Band-edge exciton in quantum dots of semiconductors with a degenerate valence band: Dark and bright exciton states. PMID- 9986446 TI - Resonant tunneling in double-quantum-well triple-barrier heterostructures. PMID- 9986447 TI - Spatial distribution of the current density and electric field in mesoscopic quantum Hall conductors. PMID- 9986448 TI - Excitons of composite fermions. PMID- 9986449 TI - Conduction- and valence-band offsets at the hydrogenated amorphous silicon carbon/crystalline silicon interface via capacitance techniques. PMID- 9986450 TI - Picosecond time evolution of free electron-hole pairs into excitons in GaAs quantum wells. PMID- 9986451 TI - Hidden massive Dirac fermions in effective field theory for integral quantum Hall transitions. PMID- 9986453 TI - Strong alignment of self-assembling InP quantum dots. PMID- 9986452 TI - Magneto-photon-phonon resonances in two-dimensional semiconductor systems driven by terahertz electromagnetic fields. PMID- 9986454 TI - Gallium-mediated homoepitaxial growth of silicon at low temperatures. PMID- 9986455 TI - Picosecond phonon dynamics and self-energy effects in highly photoexcited germanium. PMID- 9986456 TI - Effective charge-spin models for quantum dots. PMID- 9986458 TI - Duality and universality for the Chern-Simons bosons. PMID- 9986457 TI - Variational quantum Monte Carlo calculation of the effective spin Lande g factor in a two-dimensional electron system. PMID- 9986459 TI - Transition from the integer quantum Hall state to the insulator state. PMID- 9986460 TI - Magneto-optical studies of excitons in Zn1-xCdxSe/ZnSe quantum wells. PMID- 9986461 TI - Interparticle interaction in spin-aligned and spin-degenerate exciton systems and magnetoplasmas in II-VI quantum wells. PMID- 9986462 TI - Linewidth narrowing of polaritons. PMID- 9986463 TI - Quasiparticle properties of a coupled quantum-wire electron-phonon system. PMID- 9986464 TI - Exact results for interacting electrons in high Landau levels. PMID- 9986465 TI - Disorder-induced enhancement of the quantum size effects in quantum wires with a tunnel barrier. PMID- 9986466 TI - Theory of optical spectra of exciton condensates. PMID- 9986467 TI - Optical properties of passivated Si nanocrystals and SiOx nanostructures. PMID- 9986469 TI - Theory of surface vibrations in epitaxial thin films. PMID- 9986468 TI - Correlations in the interface structure of Langmuir-Blodgett films observed by x ray scattering. PMID- 9986470 TI - Step-density-wave phase of crystalline interfaces. PMID- 9986471 TI - Multilayer adsorption and desorption: Cs and Li on Ru(0001). PMID- 9986472 TI - Simple structure and soft elastic behavior of Mn on Fe{001} PMID- 9986473 TI - Exchange splitting of image states on Fe/Cu(100) and Co/Cu(100). PMID- 9986475 TI - Electronic structure, screening, and charging effects at a metal/organic tunneling junction: A first-principles study. PMID- 9986474 TI - Surface state at the K-bar point of the surface Brillouin zone on Cu{111} PMID- 9986476 TI - Optical response of C60 thin films and solutions. PMID- 9986478 TI - Inelastic and elastic processes in the transmission of F+, F-, and F2- from PF3/Ru(0001) through thin rare-gas films. PMID- 9986477 TI - Ehrlich-Schwoebel instability in molecular-beam epitaxy: A minimal model. PMID- 9986479 TI - Towards an understanding of liquid-metal embrittlement: Energetics of Ga on Al surfaces. PMID- 9986480 TI - Effects of liquid loading on surface acoustic waves in solids. PMID- 9986481 TI - High-resolution 13C NMR investigation in Cs4C60. PMID- 9986483 TI - Erratum: Surface-dimer and bulk-atom imaging of the Si(001) (2 x 1) surface by Kikuchi electron holography PMID- 9986482 TI - Density dependence of the electronic supershells in the homogeneous jellium model. PMID- 9986484 TI - Erratum: Ab initio study of hydrogen adsorption on the Si(111)-(7 x 7) surface PMID- 9986486 TI - Erratum: Electronic structure and stability of the alpha -Sn/InSb(111)A nonpolar polar heterojunction interface PMID- 9986485 TI - Erratum: Selective laser removal of the dimer layer from Si(100) surfaces revealed by scanning tunneling microscopy PMID- 9986487 TI - Electron states in a nearly ideal random-network model of amorphous SiO2 glass. PMID- 9986488 TI - Intermediate-spin state and properties of LaCoO3. PMID- 9986489 TI - Dynamical mean-field theory for perovskites. PMID- 9986490 TI - Cohesive energy of 3d transition metals: Density functional theory atomic and bulk calculations. PMID- 9986491 TI - Magnetic-electric two-dimensional Euclidean group. PMID- 9986492 TI - Electronic occupation functions for density-matrix tight-binding methods. PMID- 9986493 TI - Spectral flow in the supersymmetric t-J model with a 1/r2 interaction. PMID- 9986494 TI - GW spectral functions of Gd and NiO. PMID- 9986496 TI - Electronic structure and orbital ordering in perovskite-type 3d transition-metal oxides studied by Hartree-Fock band-structure calculations. PMID- 9986495 TI - Mutual-exclusion statistics in exactly solvable models in one and higher dimensions at low temperatures. PMID- 9986497 TI - Perturbation study on the spin and charge susceptibilities of the two-dimensional Hubbard model. PMID- 9986499 TI - Fermi-liquid-to-polaron crossover. II. Double exchange and the physics of colossal magnetoresistance. PMID- 9986498 TI - Fermi-liquid-to-polaron crossover. I. General results. PMID- 9986501 TI - Zero-bias anomaly in finite-size systems. PMID- 9986500 TI - Classical model of charge-density waves applied to mixed samples of TaS3. PMID- 9986502 TI - Phonon-drag effects on thermoelectric power. PMID- 9986503 TI - Effective medium theory of hopping transport. PMID- 9986504 TI - High resolution Compton scattering study of Be. PMID- 9986505 TI - Spin-polarized linear muffin-tin orbitals calculation of the interstitial-atom effect in gamma '-Fe4Z (Z=H, C, N). PMID- 9986506 TI - Spin-density-wave transition in systems with chemical dimerization. PMID- 9986507 TI - Valence-band electronic structure of MoS2 and Cs/MoS2(0002) studied by angle resolved x-ray photoemission spectroscopy. PMID- 9986508 TI - Gap formation and defect states in tetrahedral amorphous carbon. PMID- 9986510 TI - Self-interaction and relaxation-corrected pseudopotentials for II-VI semiconductors. PMID- 9986509 TI - Local modes of the H2* dimer in germanium. PMID- 9986511 TI - Variational quantum Monte Carlo ground state of GaAs. PMID- 9986513 TI - Possible self-trapped magnetic polaron in EuSe. PMID- 9986512 TI - Solid-state-concentration effects on the optical absorption and emission of poly(p-phenylene vinylene)-related materials. PMID- 9986514 TI - s,p-d exchange interaction in Cr-based diluted magnetic semiconductors. PMID- 9986516 TI - Photoluminescence in Zn1-xCoxSe under hydrostatic pressure. PMID- 9986515 TI - Monte Carlo study of picosecond exciton relaxation and dissociation in poly(phenylenevinylene). PMID- 9986517 TI - Origin of characteristic subgap optical absorption in CVD diamond films. PMID- 9986518 TI - Host-isotope fine structure of the fundamental and second-harmonic transitions for the CAs local mode in GaAs. PMID- 9986519 TI - Subpicosecond photoconductivity of In0.53Ga0.47As: Intervalley scattering rates observed via THz spectroscopy. PMID- 9986520 TI - Kinetics of vacancy diffusion on Si(111) surfaces studied by scanning reflection electron microscopy. PMID- 9986522 TI - First-principles study on energetics of c-BN(001) reconstructed surfaces. PMID- 9986523 TI - Electronic structure and magneto-optics of self-assembled quantum dots. PMID- 9986521 TI - Disordering of the low-temperature c(4 x 2) structure of Ge(001) to the (2 x 1) reconstruction: Evidence for a mean-field transition. PMID- 9986524 TI - Many-body effects, space-charge potential, and valence-band mixing on the optical gain in quantum-well structures. PMID- 9986525 TI - Intersubband transitions in strained In0.07Ga0.93As/Al0.40Ga0.60As multiple quantum wells and their application to a two-colors photodetector. PMID- 9986526 TI - Exciton capture by shallow quantum wells in separate confinement heterostructures. PMID- 9986527 TI - Coulomb blockade of tunneling through a double quantum dot. PMID- 9986528 TI - Microscopic theory of coherent carrier dynamics and phase breaking in semiconductors. PMID- 9986529 TI - Classical and quantum theory of a two-dimensional electron gas in time-dependent magnetic fields. PMID- 9986530 TI - Efficient, numerically stable multiband k PMID- 9986532 TI - Chemical and structural contributions to the valence-band offset at GaP/GaAs heterojunctions. PMID- 9986531 TI - Thermopower and conductivity of InAs/GaSb crossed-gap heterostructures in a magnetic field. PMID- 9986533 TI - Mobility modulation in vertical transport of hot electrons in multi-quantum-well structures. PMID- 9986535 TI - Magnetobiexcitonic states in a quantum wire. PMID- 9986534 TI - Analytic solutions for the valence subband mixing at the zone center of a GaAs/AlxGa1-xAs quantum well under uniaxial stress perpendicular to the growth direction. PMID- 9986536 TI - Theoretical studies of the effects of a magnetic field on excitonic nonlinear optical properties of quantum wires. PMID- 9986538 TI - Optical response of three-dimensional photonic lattices: Solutions of inhomogeneous Maxwell's equations and their applications. PMID- 9986537 TI - Parameters of the magnetic polaron state in diluted magnetic semiconductors Cd-Mn Te with low manganese concentration. PMID- 9986539 TI - Sum-frequency generation in a two-dimensional photonic lattice. PMID- 9986541 TI - Exchanges between group-III (B, Al, Ga, In) and Si atoms on Si(111)- sqrt(3) x sqrt(3) surfaces. PMID- 9986540 TI - Bound states and threshold resonances in quantum wires with circular bends. PMID- 9986543 TI - Momentum conservation in macroscopic quantum tunneling. PMID- 9986542 TI - Compound formation under local thermal spikes during ion-beam mixing: Model and its experimental verification. PMID- 9986544 TI - Exact critical properties of the multicomponent interacting fermion model with boundaries. PMID- 9986545 TI - Physics of noise in quantum-confined field-effect transistors. PMID- 9986547 TI - Fermi-edge singularity in nonequilibrium systems. PMID- 9986546 TI - Calculation of the residual resistivity of three-dimensional quantum wires. PMID- 9986548 TI - Ballistic weak localization in regular and chaotic quantum-electron billiards. PMID- 9986549 TI - Quantum switching of polarization in mesoscopic ferroelectrics. PMID- 9986550 TI - Effective dielectric response of semiconductor composites. PMID- 9986551 TI - Heavy-light hole mixing at zinc-blende (001) interfaces under normal incidence. PMID- 9986552 TI - Interfacial roughness and related growth mechanisms in sputtered W/Si multilayers. PMID- 9986553 TI - Four-state planar model of the Si(111) surface reconstruction. PMID- 9986554 TI - Surface-scattering study of the interaction potential of He atoms with the step edges of the Cu(211) and Cu(511) vicinal surfaces. PMID- 9986555 TI - Electronic structure of high- and low- temperature c(2 x 2)-Na/Al(001) phases from angle-scanned ultraviolet photoemission. PMID- 9986556 TI - Coverage-dependent study of the Cs/Si(100)2 x 1 surface using photoelectron spectroscopy. PMID- 9986558 TI - Kinetic Monte Carlo studies of early surface morphology in diamond film growth by chemical vapor deposition of methyl radical. PMID- 9986557 TI - Molecular dynamics of place exchange of metal adatoms with fcc (100) surfaces during deposition. PMID- 9986559 TI - Bond length and adsorbate vibrations of (2 x 3)N/Cu(110): A SEXAFS study. PMID- 9986561 TI - Self-diffusion and dynamic behavior of atoms at step edges of iridium surfaces. PMID- 9986560 TI - Anisotropic electron-beam damage and the collapse of carbon nanotubes. PMID- 9986562 TI - Relaxation of Al(001) and Al(110): Surface embedded Green function total-energy and force calculation. PMID- 9986563 TI - Monte Carlo simulations of (e,2e) experiments on solids. PMID- 9986564 TI - Ground states of a one-dimensional lattice-gas model with an infinite-range nonconvex interaction. A numerical study. PMID- 9986566 TI - Properties of pure and compound clusters of Si, Ge, and Pb. PMID- 9986565 TI - Theoretical study of icosahedral Ni clusters within the embedded-atom method. PMID- 9986567 TI - Photonic-band-structure effects for low-index-contrast two-dimensional lattices in the near-infrared. PMID- 9986569 TI - Spatial properties of nonlinear ac transport in a Luttinger liquid with an impurity. PMID- 9986568 TI - Exact solution for the general Peierls-Frohlich chain with disorder. PMID- 9986570 TI - Thermal conductivity of RB6 (R=Ce,Pr,Nd,Sm,Gd) single crystals. PMID- 9986571 TI - Ultrafast coherent transients due to exciton-continuum scattering in bulk GaAs. PMID- 9986572 TI - Impact of recombination centers on the spontaneous emission of semiconductors under steady-state and transient conditions. PMID- 9986574 TI - Manifestation of the Hofstadter butterfly in far-infrared absorption. PMID- 9986573 TI - Smooth-disorder effects in ballistic microstructures. PMID- 9986575 TI - Effect of the reduction of dimensionality on the exchange parameters in semimagnetic semiconductors. PMID- 9986577 TI - Rabi oscillations between Bloch bands. PMID- 9986576 TI - Observation of the ultrafast two-photon coherent biexciton oscillation in a GaAs/AlxGa1-xAs multiple quantum well. PMID- 9986578 TI - Tunneling through a barrier in a Tomonaga-Luttinger liquid connected to reservoirs. PMID- 9986579 TI - Phonon bottleneck in self-formed InxGa1-xAs/GaAs quantum dots by electroluminescence and time-resolved photoluminescence. PMID- 9986580 TI - Bistability and dynamic depopulation in transport through a system of weakly coupled quantum wires. PMID- 9986581 TI - Resonant Gamma -X- Gamma magnetotunneling in GaAs-AlAs-GaAs heterostructures. PMID- 9986582 TI - Transport properties of a quantum dot with superconducting leads. PMID- 9986583 TI - Fractional quantum Hall effect in bilayer two-dimensional hole-gas systems. PMID- 9986584 TI - Interface-induced conversion of infrared to visible light at semiconductor interfaces. PMID- 9986585 TI - Reversibility of the elementary mechanisms of atomic-layer epitaxy and sublimation of (001) CdTe. PMID- 9986586 TI - Attenuation of low-energy (<10 eV) O+ ions in transmission through adsorbed alkali-metal layers. PMID- 9986587 TI - Segregation-induced subsurface restructuring of FeAl(100). PMID- 9986588 TI - Local-field effects on photoemission of C60. PMID- 9986589 TI - Local transport properties of thin bismuth films studied by scanning tunneling potentiometry. PMID- 9986590 TI - Influence of dimensionality on deep tunneling rates: A study based on the hydrogen-nickel system. PMID- 9986592 TI - Ultrafast dynamics of electrons in image-potential states on clean and Xe-covered Cu(111). PMID- 9986591 TI - Electron localization in Co/Ni superlattices. PMID- 9986593 TI - Third-order elastic constants of bcc Cu-Al-Ni. PMID- 9986595 TI - Defect structure and Li-vacancy ordering in beta -LiGa. PMID- 9986594 TI - Structure and disorder in YbInCu4. PMID- 9986596 TI - Elastic properties of terbium. PMID- 9986597 TI - Arrhenius conduction restored by positional ordering of anions in the one dimensional conductor (TTF)(SCN)0.47(NO3)0.10. PMID- 9986598 TI - Phase transition in potassium dihydrogen phosphate induced by an applied static electric field. PMID- 9986599 TI - Multiphoton electron emission from Cu and W: An angle-resolved study. PMID- 9986600 TI - Martensitic phase transformation and lattice dynamics of fcc cobalt. PMID- 9986601 TI - Importance of rings on the microscopic properties of a strong glass. PMID- 9986602 TI - Splitting patterns of the electronic energy spectrum of a class of one dimensional generalized Fibonacci lattices. PMID- 9986604 TI - Homogeneous to inhomogeneous transition in charged colloids. PMID- 9986603 TI - Weak localization in an anisotropic crystal: Decagonal quasicrystal Al65Cu15Co20. PMID- 9986605 TI - Lattice dynamics of magnesium using pseudopotential and ab initio Hartree-Fock approaches. PMID- 9986606 TI - Heat-capacity comparison among the nanocrystalline, amorphous, and coarse-grained polycrystalline states in element selenium. PMID- 9986607 TI - Effective carrier doping by magnetic field into a pseudogapped state in CeNiSn: A Sn NMR study. PMID- 9986608 TI - Optical evidence of non-Fermi-liquid behavior in U1-xThxPd2Al3. PMID- 9986610 TI - Magnetic-field-induced multiple electronic states in La0.5Ca0.5MnO3+ delta. PMID- 9986609 TI - Anomalous magnetoresistance behavior of R2Ni3Si5 (R = Pr, Dy, Ho). PMID- 9986611 TI - One-dimensional free-electron spin susceptibility at finite temperature. PMID- 9986612 TI - Classical two-dimensional XXZ model: A test of a generalized self-consistent harmonic approximation. PMID- 9986613 TI - Normal modes of vortices in easy-plane antiferromagnets: Exact results and Born approximation. PMID- 9986614 TI - Observation and interpretation of a partial Gd twisted spin state in an epitaxial Gd/Fe bilayer. PMID- 9986615 TI - Giant magnetoimpedance effects in the soft ferromagnet Fe73.5CuNb3Si13.5B9. PMID- 9986616 TI - Interlayer exchange coupling in magnetic multilayers with misaligned Fermi surfaces. PMID- 9986618 TI - Nernst effect in anisotropic metals. PMID- 9986617 TI - Diffusion Monte Carlo study of two-dimensional liquid 4He. PMID- 9986619 TI - Anomalous magnetic properties in the single-crystal kappa -(BEDT-TTF)2Cu(NCS)2 superconductor. PMID- 9986621 TI - Electronic structure of Tl2Ba2CuO6+ delta epitaxial films measured by x-ray photoemission. PMID- 9986620 TI - Interlayer fluxon interaction in Josephson stacks. PMID- 9986622 TI - Superconducting transition in Nb/Gd/Nb trilayers. PMID- 9986624 TI - Influence of Van Hove singularities on the thermal conductivity of high-Tc superconductors. PMID- 9986623 TI - Observation of superconductivity in PrBa2Cu3O7. PMID- 9986625 TI - Phase diagram of Bi2.15Sr1.85CaCu2O8+ delta in the presence of columnar defects. PMID- 9986626 TI - Positive curvature in the temperature dependence of Hc2 in KxBa1-xBiO3. PMID- 9986627 TI - Raman spectra of Hg-based superconductors: Effect of oxygen defects. PMID- 9986628 TI - Optical and photoelectrical studies of charge-transfer processes in YAlO3:Ti crystals. PMID- 9986629 TI - Mesoscopic model of crack branching. PMID- 9986630 TI - Molecular motion and phase transition in K3C60 and Rb3C60 by nuclear magnetic resonance. PMID- 9986631 TI - In situ high-resolution infrared spectroscopy of a photopolymerized C60 film. PMID- 9986632 TI - Structural phase diagram of La1-xSrxMnO3+ delta : Relationship to magnetic and transport properties. PMID- 9986633 TI - Kinetics of irradiation-induced phase transformations in tricritical systems. PMID- 9986634 TI - Spectral and kinetic properties of the 4.4-eV photoluminescence band in a-SiO2: Effects of gamma irradiation. PMID- 9986635 TI - High-pressure and high-temperature studies on oxide garnets. PMID- 9986636 TI - Defect-induced condensation and the central peak at elastic phase transitions. PMID- 9986637 TI - Observation of ferroelectric domain structures by secondary-electron microscopy in as-grown KTiOPO4 crystals. PMID- 9986638 TI - Physical origin of photonic energy gaps in the propagation of surface plasmons on gratings. PMID- 9986639 TI - Thermodynamics at finite deformation of an anisotropic elastic solid. PMID- 9986640 TI - Model-independent analysis of inelastic-neutron-scattering data at high momentum transfer. PMID- 9986642 TI - Disclination dynamics in nematic liquid crystals. PMID- 9986641 TI - Spectral hole burning of Eu2+ in CaF2. PMID- 9986644 TI - Correlation between density of tunneling states and fragility of glasses. PMID- 9986643 TI - Random-network simulation of an ultracapacitor based on metal-solid-electrolyte composite. PMID- 9986645 TI - Inelastic-neutron-scattering studies on glassy and liquid Ca0.4K0.6(NO3)1.4. PMID- 9986646 TI - Photoelectron spectra of an Al70Pd21Mn9 quasicrystal and the cubic alloy Al60Pd25Mn15. PMID- 9986647 TI - Heat capacity, adsorption isotherms, and quasielastic neutron scattering measurements of bilayer deuterium hydride adsorbed on graphite. PMID- 9986648 TI - Bistable self-organization of nuclear spins in conducting solids. PMID- 9986649 TI - Classical fluctuations and anisotropy in quasi-one-dimensional antiferromagnets. PMID- 9986650 TI - Spin-one ferromagnets with single-ion anisotropy in a perpendicular external field. PMID- 9986651 TI - Dynamical correlation functions of the S=1/2 nearest-neighbor and Haldane-Shastry Heisenberg antiferromagnetic chains in zero and applied fields. PMID- 9986652 TI - Spontaneous staggered magnetization in antiferromagnetic Heisenberg-Ising chains. PMID- 9986653 TI - Two-magnon Raman scattering in a Mott-Hubbard antiferromagnet. PMID- 9986654 TI - Metallic ferromagnetism in a single-band model: Effect of band filling and Coulomb interactions. PMID- 9986655 TI - Persistent currents in coupled mesoscopic rings. PMID- 9986656 TI - Calculated oscillation periods of the interlayer coupling in Fe/Cr/Fe and Fe/Mo/Fe sandwiches. PMID- 9986658 TI - Spin excitations in the low-temperature phase of Tm. PMID- 9986657 TI - Magnetic structures of bct manganese in the bulk and at the (001) surface. PMID- 9986659 TI - Magnetic structure of dysprosium in epitaxial Dy films and in Dy/Er superlattices. PMID- 9986660 TI - ac susceptibility study on R2Fe14B single crystals (R=Y, Pr, Nd, Sm, Gd, Tb, Dy, Ho, Er, Tm). PMID- 9986661 TI - Fully relativistic spin-polarized description of magnetic interface coupling: Fe multilayers in Au(100). PMID- 9986662 TI - Magnetic excitations and soft-mode transition in the quasi-one-dimensional mixed spin antiferromagnet Pr2BaNiO5. PMID- 9986664 TI - Magnetization steps of spin quartets. PMID- 9986663 TI - Mossbauer and muon studies of beta -(NH4)2FeF5. PMID- 9986665 TI - Magnetic relaxation and formation of magnetic domains in ultrathin films with perpendicular anisotropy. PMID- 9986666 TI - Spin-wave resonance in high-conductivity films: The Fe-Co alloy system. PMID- 9986667 TI - Theory of pulsed NMR studies on solid D2. PMID- 9986668 TI - Scaling analysis of a model Hamiltonian for Ce3+ impurities in a cubic metal. PMID- 9986669 TI - Simplified hydrodynamic analysis of superfluid turbulence in He II: Internal dynamics of inhomogeneous vortex tangle. PMID- 9986670 TI - Theory of first-order layering transitions in thin helium films. PMID- 9986671 TI - Surface contribution to Raman scattering from layered superconductors. PMID- 9986673 TI - Current-voltage relation for asymmetric ballistic superconducting junctions. PMID- 9986672 TI - Influence of magnetic field and Pincus states in normal-metal-superconductor tunnel junctions. PMID- 9986674 TI - Self-field effects on flux flow in two-dimensional arrays of Nb Josephson junctions. PMID- 9986675 TI - Magnetic relaxation in a superconducting disk. PMID- 9986676 TI - Evidence of surface superconductivity in 2H-NbSe2 single crystals. PMID- 9986677 TI - Transmission resonances in a semiconductor-superconductor junction quantum interference structure. PMID- 9986679 TI - Cooper-pair tunneling in small junctions with tunable Josephson coupling. PMID- 9986678 TI - Doubly shaped D2 excitation spectra of Cs and Rb atoms in superfluid helium due to a quadrupole bubble surface oscillation. PMID- 9986680 TI - Search for negative U in the Ba1-xKxBi1-yPbyO3 system using constrained density functional theory. PMID- 9986681 TI - Effect of anisotropy on the energy gap and the critical temperature in a strongly coupled layered superconductor. PMID- 9986682 TI - Effect of nonmagnetic impurities on the gap of a dx2-y2 superconductor as seen by angle-resolved photoemission. PMID- 9986684 TI - Finite-temperature real-energy-axis solutions of the isotropic Eliashberg integral equations. PMID- 9986683 TI - Quasiparticle and spin excitations for two coupled Hubbard planes and comparison with experiments on bilayer YBa2Cu3O6+x. PMID- 9986685 TI - Vortex-liquid-vortex-crystal transition in type-II superconductors. PMID- 9986687 TI - Superconductivity of Pr2-xCexCuO4+ delta single crystals with substitution of Ni and Co on the Cu position. PMID- 9986686 TI - Seebeck and Nernst effects in the mixed state of YBa2Cu3Oy single crystals: A probe for the scattering rate of quasiparticles. PMID- 9986689 TI - Aspects of the normal-state phase of copper oxide planes in high-Tc superconductors. PMID- 9986688 TI - Doping dependence of the optical properties of Ba1-xKxBiO3. PMID- 9986690 TI - Photoemission and x-ray absorption study of superconducting and semiconducting Ba1-xKxBiO3 single crystals. PMID- 9986691 TI - Polarized and unpolarized neutron-scattering study of the dynamical spin susceptibility of YBa2Cu3O7. PMID- 9986692 TI - Raman study of the oxygen anharmonicity in YBa2Cu3Ox (6.4 m4 > m1 > m3. The highest affinities were found for N-benzyl, N-2-naphthylmethyl, and N-4-biphenylylmethyl strychnine (13, 14, and 18, respectively). All the strychnine and brucine derivatives were positively cooperative with the antagonist, N-methylscopolamine, at m2 receptors and, in the case of the strychnine analogues, were positively cooperative with N-methylscopolamine at least at one other subtype. The strychnine analogues were negatively cooperative with the neurotransmitter, acetylcholine, at all subtypes whereas brucine and five of the six derivatives examined were positively cooperative with acetylcholine at one or more subtypes (m1-m5) and exhibited different patterns of subtype selectivity. The ability to generate subtype-selective allosteric enhancers of acetylcholine binding and function may be of use in the development of drugs for the treatment of Alzheimer's disease. PMID- 9986716 TI - Synthesis of cytotoxic indenoisoquinoline topoisomerase I poisons. AB - A number of indenoisoquinolines were prepared and evaluated for cytotoxicity in human cancer cell cultures and for activity vs topoisomerase 1 (top1). The two most cytotoxic indenoisoquinolines proved to be cis-6-ethyl-5,6,12,13-tetrahydro 2,3-dimethoxy-8, 9-(methylenedioxy)-5,11-dioxo-11H-indeno[1,2-c]isoquinoline (21) and cis-6-allyl-5,6,12,13-tetrahydro-2,3-dimethoxy-8, 9-(methylenedioxy)-5,11 dioxo-11H-indeno[1,2-c]isoquinoline (22), both of which displayed submicromolar mean graph midpoints when tested in 55 human cancer cell cultures. Two of the most potent top1 inhibitors were 6-(3-carboxy-1-propyl)-5,6-dihydro-5, 11-dioxo 11H-indeno[1,2-c]isoquinoline (26) and 6-ethyl-2, 3-dimethoxy-8,9 (methylenedioxy)-11H-indeno[1,2-c]isoquinolinium chloride (27), both of which also inhibited top2, unwound DNA, and are assumed to be DNA intercalators. However, two additional potent top1 inhibitors, 6-allyl-5,6-dihydro-2,3-dimethoxy 8, 9-(methylenedioxy)-5,11-dioxo-11H-indeno[1,2-c]isoquinoline (13c) and 5,6 dihydro-6-(4-hydroxybut-1-yl)-2,3-dimethoxy-8, 9-methylenedioxy-5,11-dioxo-11H indeno[1,2-c]isoquinoline (19a), did not unwind DNA and did not affect top2. Some of the DNA cleavage sites detected in the presence of the indenoisoquinolines were different from those seen with the camptothecins. The cleavage sites induced by the indenoisoquinolines were reversed by salt treatment, which is consistent with the reversible trapping of top1 cleavable complexes by the indenoisoquinolines. In general, the potencies of the indenoisoquinolines as top1 inhibitors did not correlate with their potencies as cytotoxic agents, as some of the most cytotoxic agents had little if any effect on top1. On the other hand, the most potent of the indenoisoquinolines vs top1 were not the most cytotoxic. In several cases, moderate activity was observed for both cytotoxicity and activity vs top1. PMID- 9986717 TI - Three-dimensional quantitative structure-activity relationship analyses using comparative molecular field analysis and comparative molecular similarity indices analysis to elucidate selectivity differences of inhibitors binding to trypsin, thrombin, and factor Xa. AB - Three-dimensional quantitative structure-activity relationship (3D QSAR) methods were applied using a training set of 72 inhibitors of the benzamidine type with respect to their binding affinities (Ki values) toward thrombin, trypsin, and factor Xa to yield statistically reliable models of good predictive power. Two methods were compared: the widely used comparative molecular field analysis (CoMFA) and the recently reported CoMSIA approach (comparative molecular similarity indices analysis). CoMSIA produced significantly better results for all correlations. Furthermore, in contrast to CoMFA, CoMSIA is not sensitive to changes in orientation of the superimposed molecules in the lattice. The correlation results obtained by CoMSIA were graphically interpreted in terms of field contribution maps allowing physicochemical properties relevant for binding to be easily mapped back onto molecular structures. The advantage of this feature is demonstrated using the maps to design new molecules. Finally, the CoMSIA method was applied to elucidate structural features among ligands which are responsible for affinity differences toward thrombin and trypsin. These selectivity-determining features were interpreted graphically in terms of spatial regions responsible for affinity discrimination. Such indicators are highly informative for the lead optimization process with respect to selectivity enhancement. PMID- 9986718 TI - Flavonoid-related modulators of multidrug resistance: synthesis, pharmacological activity, and structure-activity relationships. AB - A series of 28 flavonoid derivatives containing a N-benzylpiperazine chain have been synthesized and tested for their ability to modulate multidrug resistance (MDR) in vitro. At 5 microM, most compounds potentiated doxorubicin cytotoxicity on resistant K562/DOX cells. They were also able to increase the intracellular accumulation of JC-1, a fluorescent molecule recently described as a probe of P glycoprotein-mediated MDR. This suggests that these compounds act, at least in part, by inhibiting P-glycoprotein activity. As in other studies, lipophilicity was shown to influence MDR-modulating activity but was not the only determinant. Diverse di- and trimethoxy substitutions on N-benzyl were examined and found to affect the activity differently. The most active compounds had a 2,3, 4 trimethoxybenzylpiperazine chain attached to either a flavone or a flavanone moiety (13, 19, 33, and 37) and were found to be more potent than verapamil. PMID- 9986719 TI - 1-aryl-4-[(5-methoxy-1,2,3, 4-tetrahydronaphthalen-1-yl)alkyl]piperazines and their analogues: influence of the stereochemistry of the tetrahydronaphthalen-1 yl nucleus on 5-HT1A receptor affinity and selectivity versus alpha1 and D2 receptors. 5. AB - Some 1-aryl-4-[(5-methoxy-1,2,3, 4-tetrahydronaphthalen-1-yl)-n propyl]piperazines and their alkylamino and alkylamido analogues, previously studied as 5-HT1A ligands, were prepared in enantiomerically pure form, and their absolute configuration was determined by chemical correlation or by chiroptical properties. They were evaluated for in vitro 5-HT1A, D2, and alpha1 receptor affinity by radioligand binding assays, to study the influence of the chiral carbon atom of the tetrahydronaphthalene nucleus on the 5-HT1A affinity and selectivity. Results indicated that, as regarding the 5-HT1A receptor affinity, there was no difference in affinity between (-)- and (+)-enantiomers as well as the racemate of each compound. The stereochemistry, instead, influenced the selectivity: all (-)-enantiomers displayed affinity values higher than those of (+)-isomers at D2 receptors, and conversely, all (+)-enantiomers displayed affinity values higher than those of (-)-isomers at alpha1 receptors. As a result of this trend, it is not possible to predict the isomer with a better selectivity profile. However, compounds (S)-(+)-2, (S)-(+)-4, and (R)-(+)-6 displayed high affinity for the 5-HT1A receptor (IC50 values ranging between 7.0 and 2.3 nM) and good selectivity (>/=250-fold) versus both D2 and alpha1 receptors. Furthermore, compounds (S)-(+)-4 and (R)-(-)-4 were submitted to the [35S]GTPgammaS binding assay for a preliminary evaluation of their intrinsic activity on the 5-HT1A receptor. PMID- 9986720 TI - Structure-activity relationships: analogues of the dicaffeoylquinic and dicaffeoyltartaric acids as potent inhibitors of human immunodeficiency virus type 1 integrase and replication. AB - The dicaffeoylquinic acids (DCQAs) and dicaffeoyltartaric acids (DCTAs) are potent and selective inhibitors of human immunodeficiency virus type 1 (HIV-1) integrase. They also inhibit HIV-1 replication at nontoxic concentrations. Since integrase is an excellent target for anti-HIV therapy, structure-activity relationships were employed to synthesize compounds with: (1) improved potency against HIV-1 integrase, (2) improved anti-HIV effect in tissue culture, and (3) increased selectivity as indicated by low cellular toxicity. Thirty-four analogues of the DCTAs and DCQAs were synthesized and tested for cell toxicity, anti-HIV activity, and inhibition of HIV-1 integrase. Seventeen of the 34 analogues had potent activity against HIV-1 integrase ranging from 0. 07 to >10 microM. Seventeen analogues that were synthesized or purchased had no inhibitory activity against integrase at concentrations of 25 microM. Of the biologically active analogues, 7 of the 17 inhibited HIV replication at nontoxic concentrations. The most potent compounds were D-chicoric acid, meso-chicoric acid, bis(3,4-dihydroxydihydrocinnamoyl)-L-tartaric acid, digalloyl-L-tartaric acid, bis(3,4-dihydroxybenzoyl)-L-tartaric acid, dicaffeoylglyceric acid, and bis(3, 4-dihydroxyphenylacetyl)-L-tartaric acid. Anti-HIV activity of the active compounds in tissue culture ranged from 35 to 0.66 microM. Structure-activity relationships demonstrated that biscatechol moieties were absolutely required for inhibition of integrase, while at least one free carboxyl group was required for anti-HIV activity. These data demonstrate that analogues of the DCTAs and the DCQAs can be synthesized which have improved activity against HIV integrase. PMID- 9986721 TI - Novel antitumor 2-cyanoaziridine-1-carboxamides. AB - A set of 20 2-cyanoaziridine-1-carboxamides was synthesized from 2-cyanoaziridine and appropriate isocyanates. These compounds were active against a variety of solid and hematological tumor cells in culture, including strains resistant to doxorubicin and mitoxantrone. Their potencies in these assays correlated with the lipophilicity of substituents. The N-phenyl derivative was more potent and equally effective to imexon, a cyclized 2-cyanoaziridine-1-carboxamide of clinical interest, against cloned fresh human tumors. PMID- 9986722 TI - Metallopeptidase inhibitors of tetanus toxin: A combinatorial approach. AB - The bacterial protein tetanus toxin (TeNt), which belongs to the family of zinc endopeptidases, cleaves synaptobrevin, an essential synaptic protein component of the neurotransmitter exocytosis apparatus, at a single peptide bond (Gln76 Phe77). This protease activity is a particularly attractive target for designing potent and selective synthetic inhibitors as a possible drug therapy for tetanus. beta-Aminothiols mimicking Gln76 of synaptobrevin have been previously shown to inhibit the tetanus neurotoxin enzymatic activity in the 35-250 microM range. These compounds have now been modified to interact with S' subsites of the TeNt active site, with the aim of increasing their inhibitory potencies. Combinatorial libraries of pseudotripeptides, containing an ethylene sulfonamide or an m sulfonamidophenyl moiety as the P1 side chain and natural amino acids in P1' and P2' positions, were synthesized. The best inhibitory activity was observed with Tyr and His as P1' and P2' components, respectively. This led to new inhibitors of TeNt with Ki values in the 3-4 microM range. These molecules are the most potent inhibitors of TeNt described so far. PMID- 9986724 TI - Assistance in Manuscript Presentation. PMID- 9986723 TI - N-Methyl-5-tert-butyltryptamine: A novel, highly potent 5-HT1D receptor agonist. AB - It has been observed that reported 5-HT1D receptor agonists have at least one heteroatom (N, O, or S) on the 5-substituent of the indole. This has led to the hypothesis that a 5-substituent capable of participating in hydrogen bonding is critical for conveying high affinity. This article describes the synthesis and biological evaluation of a new series of 5-alkyltryptamine analogues, which does not have a heteroatom in the 5-substituent group. In contrast to the hypothesis, 5-alkyltryptamines all exhibit high binding affinities for the human 5-HT1D receptor. The size of the lipophilic alkyl group at the 5-position of the indole has significant impact on the 5-HT1D binding affinity. Compounds with a tert butyl group at the 5-position such as 9d, 10, and 11 were identified. These analogues display high binding affinity (Ki < 1 nM) and moderate receptor selectivity in comparison with known antimigraine agents such as sumatriptan, naratriptan, rizatriptan, and VML-251. PMID- 9986725 TI - ANTHERIDIAL CHROMATIN CONDENSATION FACTOR FROM MALE SEX ORGANS OF CHARA TOMENTOSA. AB - Incubation of roots (Melandrium noctiflorum) in crude extracts obtained from maturing male sex organs of Chara tomentosa results in supercondensation of mitotic chromosomes. The observed changes, including a number of 'secondary effects', confirm precisely with all those kinds of alterations which are typical of M-phase cells in antheridial filaments during their progression from the proliferative period of development towards terminal differentiation into sperm cells. Biological assays performed with proteinaceous extracts of maturing antheridia indicate that the activity is confined merely to a fraction containing low molecular (4.5 kDa) peptides, termed as ACCF (antheridial chromatin condensation factor). Microchemical tests showed the acidic character of ACCF and its apparent ability to form cross-links with histones and DNA-histone complexes, mediated presumably by disulfide bridges. The characteristic punctate distribution of vesicles within the cytoplasm suggests the internalization of rhodamine-isothiocyanate labelled ACCF (ACCF-TRITC) by endocytosis, implying possible sequestering and nuclear translocation upon release from the endosomal/lysosomal compartment of the cell. Copyright 1998 Academic Press. PMID- 9986726 TI - Processing of the sperm protein Sp17 during the acrosome reaction and characterization as a calmodulin binding protein. AB - In this study we have demonstrated that the native rabbit sperm protein, Sp17, is a 22- to 24-kDa triplet of proteins in washed ejaculated rabbit spermatozoa and is unaffected by capacitation. However, during the acrosome reaction, Sp17 is processed from a 22- to 24-kDa triplet of proteins to a triplet of proteins at 17 19 kDa by the removal of amino acids from the C-terminal. Recombinant rabbit Sp17 (rRSp17) can also be proteolytically processed by acrosome-reacted spermatozoa in a similar manner. Protease inhibitors prevent the proteolytic processing of Sp17. Both forms of native Sp17 remain associated with acrosome-reacted spermatozoa and are solubilized by ionic detergents. Previously, sequence analysis of Sp17 revealed that Sp17 amino acids 108-137 were 52% identical to the calmodulin binding domain of neuromodulin and contained an IQ motif found in other calmodulin binding proteins. In this study, a truncated recombinant Sp17, rRSp17CB, which lacks amino acids 118-146, including the potential calmodulin binding site, was made. Recombinant rabbit Sp17, but not rRSp17CB, binds to calmodulin in the presence of Ca2+ or EDTA, under reduced or nonreduced conditions in biotinylated-calmodulin overlay assays. In DSS crosslinker experiments, calmodulin bound to rRSp17 in a 1:1 ratio but not to rRSp17CB. Additionally, biotinylated rRSp17 interacts with native sperm calmodulin. We propose that the processing of native Sp17, by removing a C-terminal fragment during the acrosome reaction, might be a mechanism to regulate the calmodulin binding activity of Sp17 and provide calmodulin at specific sites after the acrosome reaction. PMID- 9986727 TI - Vezf1: A Zn finger transcription factor restricted to endothelial cells and their precursors. AB - Using retroviral entrapment vectors, we identified a novel mouse gene whose expression is restricted to vascular endothelial cells and their precursors in the yolk sac blood islands. A 3.68-kb cDNA corresponding to the endogenous transcript was isolated using genomic DNA flanking the entrapment vector insertion as a probe. We have named this gene Vezf1 for vascular endothelial zinc finger 1. Vezf1 encodes a protein with a predicted molecular mass of 56 kDa and that contains six putative zinc finger domains and shows high homology to a previously identified human gene, DB1, that is believed to be involved in regulating expression of cytokine genes such as interleukin-3. In situ hybridization analysis revealed the onset of expression in advanced primitive streak-stage embryos being located in the extraembryonic mesodermal component of the visceral yolk sac and in the anteriormost mesoderm of the embryo proper. During head-fold and somite stages, expression was restricted to vascular endothelial cells that arise during both vasculogenesis and angiogenesis. Vezf1 related sequences were found to be highly conserved among higher vertebrate species that have acquired extraembryonic yolk sac membranes during evolution. The Vezf1 locus mapped to the proximal part of mouse chromosome 2, a region which has homology to human chromosome 9q. Vezf1 expression correlates temporally and spatially with the early differentiation of angioblasts into the endothelial cell lineage and the proliferation of endothelial cells of the embryonic vascular system. Thus, Vezf1 may play an important role in the endothelial lineage determination and may have an additional role during later stages of embryonic vasculogenesis and angiogenesis. PMID- 9986728 TI - The LIN-29 transcription factor is required for proper morphogenesis of the Caenorhabditis elegans male tail. AB - The Caenorhabditis elegans gene lin-29 encodes a zinc-finger transcription factor that is required for hypodermal cell terminal differentiation and proper vulva morphogenesis. Here we demonstrate that lin-29 is also required in males for productive mating. We show that lin-29 males can perform the early mating behaviors including response to hermaphrodite contact and vulva location, but they do not perform the subsequent steps of vulva attachment via spicule insertion and sperm transfer. Consistent with this observation, we found that lin 29 mutant spicules are on average 43% shorter than wild-type spicules while other male mating structures appear unaltered. In lin-29 mutants, spicule development goes awry after the generation of spicule cells, when spicule morphogenesis occurs in wild-type males. We show that LIN-29 accumulates in many cells of the wild-type male tail, including those that form the spicules. We demonstrate, through analysis of genetic mosaics, that the formation of wild-type-length spicules requires lin-29(+) in the AB.p lineage, the lineage that gives rise to the spicules and other male copulatory structures. Our mosaic analysis also reveals a role for lin-29(+) in the P1 lineage, which mainly produces sex muscles, cells of the somatic gonad, and body wall muscles. PMID- 9986730 TI - Intracellular calcium release channel expression during embryogenesis. AB - The release of intracellular calcium (Ca2+) via either inositol 1,4, 5 trisphosphate receptors (IP3R) or ryanodine receptors (RyR) activates a wide variety of signaling pathways in virtually every type of cell. In the present study we demonstrate that at early stages of development IP3R mRNA and functional IP3-gated Ca2+ release channels are widely expressed in virtually all tissues in murine embryos. As organogenesis proceeds, more specialized RyR channels are expressed in many cell types and the triggering mechanisms for intracellular Ca2+ release become more diverse to include IP3-dependent and voltage-dependent and Ca2+-induced Ca2+ release. As development proceeds virtually all cell types continue to express IP3R channels but in excitable cells including skeletal and cardiac muscles the major Ca2+ release channels are RyRs. This developmental switch from predominantly IP3-mediated to both IP3-mediated and IP3-independent pathways for intracellular Ca2+ release is consistent with data showing that IP3R plays an important regulatory role in cellular proliferation and apoptosis, whereas RyR is required for other cellular functions including muscle contraction. PMID- 9986729 TI - Bone morphogenetic protein antagonism of Spemann's organizer is independent of Wnt signaling. AB - The Xenopus homeobox gene twin is involved in the Wnt-mediated induction of Spemann's organizer. Additionally, several lines of evidence indicate that bone morphogenetic proteins (BMPs) play a role in repressing the formation of the organizer by antagonizing the expression of genes involved in organizer establishment. In order to determine at what level BMPs exert their effect, we measured the activity of different genes expressed within the organizer region. We report that BMP signaling can antagonize the induction of the dorsal-specific gene goosecoid but is unable to affect Wnt signaling at the level of twin. These results suggest that the antagonistic activities of BMPs in organizer formation occur postzygotically, independent of twin regulation, and that Wnt-like dorsal determinant signaling pathways do not crosstalk with BMPs. PMID- 9986731 TI - The dominant mutation Glazed is a gain-of-function allele of wingless that, similar to loss of APC, interferes with normal eye development. AB - Dominant mutations have served as invaluable tools for Drosophila geneticists. Here we analyze the dominant eye mutation Glazed (Gla) that was described by T. H. Morgan more than 50 years ago. We show that Gla causes the loss of photoreceptor cells during pupal stages, in a process reminiscent of apoptosis, with a concomitant overproduction of eye pigment. This phenotype is very similar to that caused by the loss of D-APC, a negative regulator of Wingless (Wg) signal transduction. Genetic analyses reveal however that the Gla gain-of-function phenotype can be reverted to wild-type. By generating a P-element-induced revertant of Gla we demonstrate that Gla is allelic to wg. The molecular lesion in Gla indicates that the insertion of a roo retrotransposon leads to ectopic expression of wg during pupal stages. We show that the Gla phenotype is similar to that caused by ectopic expression of Wg driven by the sevenless (sev) enhancer. In both cases Wg exerts its effect, at least in part, by negatively regulating the expression of the Pax2 homolog sparkling (spa). Gla represents not only the first dominant allele of wg, but it may also be the first allele ever described for wg. PMID- 9986732 TI - A role for DNA methylation in gastrulation and somite patterning. AB - DNA methylation constitutes an important epigenetic factor in the control of genetic information. In this study, we analyzed expression of the DNA methyltransferase gene and examined DNA methylation patterns during early development of the zebrafish. Maternal transcripts of the zebrafish DNA methyltransferase gene (MTase) are ubiquitously present at high levels in early embryos with overall levels decreasing after the blastula stage. At 24 h, methyltransferase mRNA is predominantly found in the brain, neural tube, eyes, and differentiating somites. Expression of MTase in the somites is highest in the anterior cells of the somites. Despite the high levels of MTase mRNA in blastula stage embryos, we observe DNA hypomethylation at the blastula and gastrula stages compared to sperm or older embryos. Zebrafish embryos treated with 5-azacytidine (5-azaC) and 5-aza-2-deoxycytidine (5-azadC), nucleotide analogs known to induce cellular differentiation and DNA hypomethylation in mammalian cells, exhibit DNA hypomethylation and developmental perturbations. These defects are specifically observed in embryos treated at the beginning of the blastula period, just prior to midblastula transition. The most common phenotype is the loss of tail and abnormal patterning of somites. Head development is also affected in some embryos. Histological and in situ hybridization analyses reveal whole or partial loss of a differentiated notochord and midline muscle in treated embryos. When examined during gastrulation, 5-azaC-treated embryos have a shortened and thickened axial mesoderm. We propose that DNA methylation is required for normal gastrulation and subsequent patterning of the dorsal mesoderm. PMID- 9986733 TI - Retinoid signaling required for normal heart development regulates GATA-4 in a pathway distinct from cardiomyocyte differentiation. AB - Vitamin A is essential for normal embryonic cardiogenesis. The vitamin A deficient phenotype in the avian embryo includes an abnormal heart tube closed at the sinus venosus and the absence of large vessels that normally connect the embryonic heart to the developing circulatory system. In vitamin A-deficient embryos the expression of cardiomyocyte differentiation genes, including atrial specific myosin heavy chain, ventricular-specific myosin, and sarcomeric myosins as well as the putative cardiomyocyte specification gene Nkx-2.5, is not altered. However, the expression of transcription factor GATA-4 is severely decreased in the heart-forming regions of vitamin A-deficient stage 7-10 embryos. Significantly, GATA-4 transcripts are completely lacking in the lateral mesoderm posterior to the heart, in the area of the developing cardiac inflow tract that later displays prominent morphological defects, including a closed nonseptated heart lacking a sinus venosus. The administration of retinol to the vitamin A deficient embryo restores GATA-4 expression and completely rescues the vitamin A deficient phenotype. Our results indicate that GATA-4 is a component of the retinoid-mediated cardiogenic pathway unlinked to cardiomyocyte differentiation, but involved in the morphogenesis of the posterior heart tube and the development of the cardiac inflow tract. PMID- 9986734 TI - Myogenic determination occurs independently in somites and limb buds. AB - Gene targeting has indicated that the bHLH transcription factors Myf-5 and MyoD are required for myogenic determination because skeletal myoblasts and myofibers are entirely ablated in mouse embryos lacking both Myf-5 and MyoD. Entrance into the skeletal myogenic program during development occurs following the independent transcriptional induction of either Myf-5 or MyoD. To identify sequences required for the de novo induction of MyoD transcription during development, we investigated the expression patterns of MyoD-lacZ transgenes in embryos deficient in both Myf-5 and MyoD. We observed that a 258-bp fragment containing the core of the -20-kb MyoD enhancer activated expression in newly formed somites and limb buds in compound mutant embryos lacking both Myf-5 and MyoD. Importantly, Myf-5- and MyoD-deficient presumptive muscle precursor cells expressing beta galactosidase were observed to assume nonmuscle fates primarily as precartilage primordia in the trunk and the limbs, suggesting that these cells were multipotential. Therefore, cells are recruited into the MyoD-dependent myogenic lineage through activation of the -20-kb MyoD enhancer and this occurs independently in somites and limb buds. PMID- 9986735 TI - Identification of PLCgamma-dependent and -independent events during fertilization of sea urchin eggs. AB - At fertilization, sea urchin eggs undergo a series of activation events, including a Ca2+ action potential, Ca2+ release from the endoplasmic reticulum, an increase in intracellular pH, sperm pronuclear formation, MAP kinase dephosphorylation, and DNA synthesis. To examine which of these events might be initiated by activation of phospholipase Cgamma (PLCgamma), which produces the second messengers inositol trisphosphate (IP3) and diacylglycerol, we used recombinant SH2 domains of PLCgamma as specific inhibitors. Sea urchin eggs were co-injected with a GST fusion protein composed of the two tandem SH2 domains of bovine PLCgamma and (1) Ca2+ green dextran to monitor intracellular free Ca2+, (2) BCECF dextran to monitor intracellular pH, (3) Oregon Green dUTP to monitor DNA synthesis, or (4) fluorescein 70-kDa dextran to monitor nuclear envelope formation. Microinjection of the tandem SH2 domains of PLCgamma produced a concentration-dependent inhibition of Ca2+ release and also inhibited cortical granule exocytosis, cytoplasmic alkalinization, MAP kinase dephosphorylation, DNA synthesis, and cleavage after fertilization. However, the Ca2+ action potential, sperm entry, and sperm pronuclear formation were not prevented by injection of the PLCgammaSH2 domain protein. Microinjection of a control protein, the tandem SH2 domains of the phosphatase SHP2, had no effect on Ca2+ release, cortical granule exocytosis, DNA synthesis, or cleavage. Specificity of the inhibitory action of the PLCgammaSH2 domains was further indicated by the finding that microinjection of PLCgammaSH2 domains that had been point mutated at a critical arginine did not inhibit Ca release at fertilization. Additionally, Ca2+ release in response to microinjection of IP3, cholera toxin, cADP ribose, or cGMP was not inhibited by the PLCgammaSH2 fusion protein. These results indicate that PLCgamma plays a key role in several fertilization events in sea urchin eggs, including Ca2+ release and DNA synthesis, but that the action potential, sperm entry, and male pronuclear formation can occur in the absence of PLCgamma activation or Ca2+ increase. PMID- 9986736 TI - Autofluorescence of the diabetic and healthy human cornea in vivo at different excitation wavelengths. AB - Corneal autofluorescence is higher in diabetes mellitus patients with retinopathy than in healthy subjects. In this study, the excitation spectra of corneal autofluorescence of diabetic patients and healthy controls in the range 365 nm 480 nm were compared in an attempt to identify the fluorophores responsible for corneal autofluorescence in health and disease (diabetes). Spectral measurements (from one eye) were recorded from five patients with proliferative diabetic retinopathy and five age-matched healthy controls, using a modified commercial scanning fluorophotometer with a mercury arc or a tungsten halogen lamp as excitation light source in combination with interference filters (excitation wavelengths: 365, 405, 420, 430, 436, 440, 450, 470 and 480 nm; bandwidth: 10 nm). Fluorescence emission was measured in the range 532 nm-630 nm. The sensitivity of the modified fluorophotometer was calibrated by using the excitation spectrum of fluorescein as a reference. The corneal excitation efficiency of the diabetic patients was higher than that of the healthy controls at each wavelength investigated (Mann-Witney test P<0.0005). The ratio between the mean values of both groups was equal for each excitation wavelength (mean ratio 1.9+/-0.12s.d.,P>0. 2), suggesting that the excitation spectra were equal. This indicates that the same fluorophores are responsible for the corneal autofluorescence in both groups. The shapes of the excitation spectra suggest the involvement of flavins, NAD(P)H, and at least one other, as yet unidentified, fluorophore. PMID- 9986737 TI - Differing roles of adenosine receptor subtypes in retinal ischemia-reperfusion injury in the rat. AB - Adenosine has been shown to be a major component of the retina's endogenous reaction to ischemia. In earlier studies, the significant changes in adenosine concentration that occur during ischemia and the ensuing reperfusion period were documented. While previous studies have shown that adenosine is a mediator of the changes in blood flow that occur in response to ischemia, hypoxia, and hypoglycemia in the retina, little is known about other functional effects that result from these changes in adenosine concentration. Accordingly, the influence of adenosine receptor blockade on the functional and histological outcome following ischemia in rats was examined. Specific antagonists of the adenosine A1 and A2a receptors were injected systemically, prior to ischemia of either 5, 30, or 60 min. The recovery of the electroretinogram a and b waves was followed for up to 7 days after ischemia, and retinal structure was examined by light microscopy. The adenosine A1 receptor antagonist DPCPX attenuated recovery after retinal ischemia of either 5 or 30 min, while the A2a receptor antagonist CSC dramatically protected retinal function and structure even with ischemia lasting up to 60 min. It was concluded that blockade of the A2a receptor, possibly combined with stimulation of the A1 receptor, may represent a potential new strategy for the prevention of ischemic damage in the retina. PMID- 9986738 TI - Basic FGF-induced down-regulation of IGF-I mRNA in cultured rat Muller cells. AB - Interactions among growth factors are important in a variety of physiological and pathological processes. The regulation of IGF-I mRNA expression by bFGF was investigated in cultured rat Muller cells and the mechanism of regulation studied. Muller cells from 1- to 3-day-old Sprague-Dawley rats were isolated and cultured with Eagle MEM+10% FCS. Cultured cells were identified by immunocytochemistry using antibodies against vimentin, carbonic anhydrase C, and glutamine synthetase. Cells of passage 1-4 were treated with bFGF, the PKC inhibitor H-7, calphostin C, the PKC activator PMA or the PKA inhibitor H-89, as well as the adenylate cyclase activator forskolin, or adenylate cyclase inhibitor SQ22536. IGF-I and bFGF expression levels were assessed by Northern blot analysis. The addition of bFGF to culture medium down-regulated IGF-I expression in a dose- and time-dependent manner. Decrease of IGF-I expression started at a bFGF concentration of 1 ng ml-1. IGF-I mRNA level declined to 44% of baseline level at 10 ng ml-1 of bFGF, and reached a trough of 40% at 50 ng ml-1. At 10 ng ml-1 of bFGF, down-regulation of IGF-I expression was observed as early as 4 hr (60%) after treatment, and reached a trough of 42% by 8 hr. The temporal and concentration dependence of IGF-I expression by addition of the PKC activator PMA, to culture medium was similar to that due to the addition of bFGF. The down regulation of IGF-I expression by bFGF (10 ng ml-1) and PMA (0.1 microM) was blocked by the PKC inhibitors H-7 (30 microM) and calphostin C (1 microM). Forskolin (5 microM), an adenylate cyclase activator, had activator, had no effect on IGF-I expression. SQ22536 (100 microM), an adenylate cyclase inhibitor, and H-89, a PKA inhibitor, had no inhibitory effect on bFGF-induced down regulation of IGF-I expression. These results indicate that bFGF down-regulates IGF-I expression in cultured rat M uller cells through PKC activation. PMID- 9986739 TI - Enhanced tenascin expression associated with reactive astrocytes in human optic nerve heads with primary open angle glaucoma. AB - Tenascin is a large extracellular matrix glycoprotein expressed in neural and non neural tissues. In the central nervous system, tenascin is synthesized by astrocytes during development and wound healing, forming barriers and affecting neurite outgrowth. In this study we examined tenascin expression in optic nerve heads of normal and glaucomatous eyes and found that there is upregulation of tenascin mRNA and protein in reactive astrocytes from human glaucomatous optic nerve heads compared to normal age-matched controls. In the prelaminar region there was a band of tenascin immunoreactivity around the blood vessels of glaucomatous, but not in normal eyes. However, tenascin mRNA was only localized to astrocytes, suggesting that astrocytes are the cellular source of tenascin. In the lamina cribrosa, tenascin immunoreactivity and gene expression were localized to astrocytes in the cribriform plates and inside the nerve bundles. In the post lamina region, tenascin immunoreactivity and gene expression were localized to astrocytes lining the pial septum immediately adjacent to the lamina cribrosa. In normal optic nerve heads, tenascin expression at the mRNA and protein levels was confined to clusters of astrocytes at the level of Bruch's membrane in the prelaminar optic nerve head. In glaucoma, enhanced expression of tenascin may be protective to the axons of the retinal ganglion cells by providing a barrier for humoral and/or blood-borne factors that may cause further neural damage. However, the precise role of tenascin in glaucomatous optic neuropathy is not yet elucidated. PMID- 9986740 TI - Localization of MIP 26 in nuclear fiber cells from aged normal and age-related nuclear cataractous human lenses. AB - The purpose of the current study was to localize the lens membrane protein, MIP 26, in nuclear fiber cells from different regions of aged normal and age-related cataractous human lenses. Adult, juvenile, fetal and embryonic nuclear regions in aged normal and age-related nuclear cataractous lenses were morphologically and biochemically characterized using the technologies of immuno-gold (5 nm) labeling, semi-thin sections (200-500 nm), serial sections, DiI staining following by photobleaching, transmission electron microscopy and spot-blot analysis. Numbers of gold particles per micron length of plasma membrane and numbers of gold particles per square micron of cytosol in the embryonic-fetal and juvenile-adult nuclear regions were quantified. Results showed that the labeling pattern of MIP 26 localized to the cytosol was unique to senescent fiber cells from age-related cataractous lenses. Numbers of gold particles per square micron of cytosol in the embryonic-fetal nucleus of age-related cataractous lenses were significantly elevated (P<0.001) above numbers from fiber cells located within the adult or juvenile nuclei of the same lens or senescent fiber cells from aged normal lenses. Some of the cytosolic labeling in cataracts was localized to lipid vesicles, while the remaining labeling was negative for the lipid specific stain DiI. Spot blot analysis demonstrated that binding of the ant-MIP 26 serum was exclusive to large molecular weight components greater than 10 kDa, and not to small molecular weight fragments of the protein. The results of the current study supply further evidence that damage to membranes occurs in senescent fiber cells during age-related nuclear cataracts, resulting in the internalization of structures containing the membrane protein MIP 26. PMID- 9986741 TI - An immunohistochemical study of an autosomal dominant feline rod/cone dysplasia (Rdy cats). AB - An autosomal dominant, early onset feline model of rod/cone dysplasia has been described. The clinical features, light and electron microscopy, and the electrophysiology were documented. We have now examined in more detail the histopathological and immunohistochemical changes during the early phase of the disease using antibodies against opsin, synaptophysin, glial fibrillary acidic protein (GFAP) and an epithelial marker (MNF118). We have also demonstrated programmed cell death by a modified TUNEL (Terminal deoxynucleotidyl transferase, Uridine triphosphate, Nick End Labelling) technique. In the Rdy cats, there was significant photoreceptor degeneration between 5 and 17 weeks of age. The TUNEL labeled cell and pyknotic cell counts in the outer nuclear layer peaked at around 9 weeks of age. Accumulation of opsin in the entire outer nuclear layer of the retina was noted with opsin-immunolabeled rod neurite sprouting. There was a reduction in synaptophysin immunoreactivity in the outer plexiform layer. The Muller cells were activated and expressed GFAP. No significant change of immunolabeling of MNF118 was found. These findings closely parallel those seen in human RP. PMID- 9986742 TI - X-ray microanalysis of melanin granules of retinal pigment epithelium and choroid in hereditary copper deficient mice (macular mice). AB - The role of trace elements in vivo has not been completely clarified. Trace elements were studied in melanin granules in the retinal pigment epithelium (RPE) and choroid of hereditary copper-deficient macular mice as a model of Menkes' disease. The analysis of elements in these melanin granules was done by new methods: freeze-embedding and an energy dispersive X-ray microanalysis (EDX). We used 14-day- and 1-month-old male hemizygote macular mice for the experiments and normal litter-mates as controls. Melanin granules in RPE and choroid contained sulfur, chloride, calcium, iron, copper and zinc. Calcium and copper were especially abundant in 14-day-old hemizygote macular mice, although there were few melanin granules in their RPE. The fact that copper was most abundant in the melanin granules in the RPE of 14-day-old macular mice suggests that the synthesis of melanin granules in the RPE and choroid of the hemizygote macular mice cannot be completed because of the lower activity of copper-containing enzymes such as tyrosinase and the abnormal copper distribution in various organs. Therefore, the melanin granules in the RPE and choroid of hemizygote macular mice are irregular in shape and few in number. Large amounts of copper concentrated in melanin granules in the RPE and choroid of hemizygote macular mice might induce quantitative abnormalities of trace elements. PMID- 9986743 TI - Partial and full-thickness neuroretinal transplants. AB - Adult and embryonic rabbit retinal sheets were transplanted into the subretinal space of adult rabbits. The transplants were either full-thickness with intact layering, or gelatin embedded and vibratome sectioned with the inner retina removed. The full-thickness grafts were positioned subretinally by means of a glass capillary in which they were partially folded. The vibratome sectioned ones were placed using a plastic injector in which the gelatin embedded graft was flat. The embryonic full-thickness grafts were followed clinically up to 3 months, and the other 3 transplant types up to 1 month postoperatively, after which the retina was sectioned and stained for light microscopy. Surgical complications were more common in eyes receiving vibratome sectioned grafts with 10 out of 34 eyes displaying blood in the vitreous. Four of these eyes also developed total retinal detachment. Out of 17 eyes receiving full-thickness grafts, only one displayed these complications. Histologically, 11 out of 13 embryonic full-thickness transplants revealed straight, laminated transplants with correct polarity, and with all normal retinal layers present. In these transplants, fusion with the host increased in time. Of the adult full-thickness transplants, only 1 out of 4 survived, and this graft showed signs of degeneration. The vibratome sectioned adult transplants in a few cases survived the first two postoperative weeks. In these grafts, both inner and outer retina were present, indicating an incomplete vibratome sectioning. With longer postoperative times, the number of surviving transplants in this group diminished considerably. All vibratome sectioned embryonic transplants developed into rosettes and sometimes also into laminated sections with reversed polarity. It can be concluded that in rabbits, the surgical technique used for vibratome sectioned transplants requires a larger sclerotomy and retinotomy, since they have to be kept flat in the transplanting instrument due to the surrounding gelatin. This technique is associated with a higher frequency of complications than the one used for full-thickness grafts which are more flexible and can be transplanted with a smaller instrument. Vibratome sectioning of embryonic grafts results in abnormal morphology and their adult counterparts only survive if the sectioning is incomplete. Adult full-thickness grafts show poor survival. Embryonic full-thickness transplants in the majority of cases develop into laminated retinas with layers parallel to the host retinal pigment epithelium. They also survive and integrate well with the host retina. PMID- 9986744 TI - Morphological changes of retinal pigment epithelium and choroid in rd-mice. AB - The sequence of degenerative changes in the retinal pigment epithelium (RPE) and the choroid of retinal degeneration (rd)-mice was studied in correlation with photoreceptor changes. Three weeks to 26-month-old animals were investigated using light and transmission electron microscopy, enzyme histochemistry and quantitative morphology. Changes in the choriocapillaris (CC) were additionally studied by scanning electron microscopy of corrosion cast preparations. In 3-week old mice, in which most of the outer segments of photoreceptors in the central portion of the retina had disappeared but remnants of the cells were still present, the RPE was enlarged and showed elongated microvilli. In 8-week-old animals, the photoreceptors were completely absent in large areas of the posterior pole region. In these areas the RPE was also completely lost. Quantitative evaluation performed in histological serial sections showed that loss of RPE measured as length of RPE-free Bruch's membrane, continuously increased up to the age of 20 months. In 8-week-old animals, CC adjacent to degenerating RPE showed loss of fenestration. In 10-week-old animals, the CC disappeared in those areas where the RPE was already lacking. The loss of CC increased with increasing age and in 20-month-old animals 5-10% of the entire CC was lacking. Loss of the related arterioles and nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d)-positive nerve fibers occurred only in approximately 2-year-old rd-mice. Compared to other animal models, RPE and CC defects in rd-mice are relatively large. The rd-mice might therefore provide a good tool to study factors involved in CC degeneration. PMID- 9986745 TI - alpha-Methyl-p-tyrosine inhibits latanoprost-induced melanogenesis in vitro. AB - The PGF2alpha derivative, latanoprost, is a recent anti-glaucoma drug that has been reported to induce a discrete incidence of increased iris pigmentation in men. The present experiments were made in order to study whether this phenomenon could be influenced by the tyrosinase inhibitor, alpha-methyl-p-tyrosine. Melanin content, melanin production and tyrosinase activity of cultured uveal melanocytes derived from irides of brown or brown-blue color were measured after adding latanoprost at different molar concentration with or without alpha-methyl-p tyrosine (10(-5)m). It was shown that latanoprost stimulated melanin content, melanin production and tyrosinase activity in a molar range between 10(-7) and 10(-5)m in uveal melanocytes derived from irides of both brown and brown-blue color. The effect seemed to be more pronounced in melanocytes derived from irides of brown-blue color. The adding of alpha-methyl-p-tyrosine completely prevented latanoprost-induced stimulation of melanin production in uveal melanocytes derived from irides of both colors. These results suggest that latanoprost induced stimulation of melanin production, follows the metabolic pathway involving tyrosinase activity and may be relevant for the therapeutic application of latanoprost in glaucoma in order to reduce its side-effect resulting in increased iris pigmentation. PMID- 9986746 TI - Predominance of MMP-1 and MMP-2 in epiretinal and subretinal membranes of proliferative vitreoretinopathy. AB - Matrix metalloproteinases (MMPs) and their natural inhibitors (TIMPs) play an important role in matrix remodelling and their involvement in the formation of scar-like tissue in proliferative vitreoretinopathy (PVR) is unknown. In this study we investigated epiretinal and subretinal membranes of PVR for the presence of selected MMPs and TIMPs whose substrates are extracellular matrix components of these membranes. We examined 23 epiretinal membranes and 15 subretinal membranes of PVR for deposition of interstitial collagenase (MMP-1), stromelysin 1 (MMP-3), gelatinase A (MMP-2), gelatinase B (MMP-9) and two tissue inhibitors of metalloproteinases (TIMP-1 and TIMP-2) by immunohistochemical methods. Normal cadaveric retinas served as controls. We observed that a large proportion of epiretinal and subretinal membranes stained for MMP-1 and MMP-2, whilst MMP-3, MMP-9, TIMP-1 and TIMP-2 were only observed in a small proportion of specimens. Normal cadaveric retinas stained for MMP-1 but not for MMP-2, MMP-3, MMP-9 or TIMP-1. TIMP-2 positive cells were observed within the inner and outer nuclear cell layers of normal retina. Presence of MMP-2, MMP-3 and TIMP-1 in epiretinal and subretinal membranes of PVR but not in normal retina indicates that these molecules may play an important role during the healing process that follows rhegmatogenous retinal detachment. An understanding of the mechanisms that control production and activity of these enzymes and their inhibitors may aid in the design of new therapeutic approaches to treat and prevent PVR. PMID- 9986747 TI - Truncation of betaA3/A1-crystallin during aging of the bovine lens; possible implications for lens optical quality. AB - During aging, extensive modifications of eye lens proteins take place, which may contribute to the development of cataract. Truncation of the accessible extensions of beta-crystallins has been suggested to be an important factor in this process. We therefore studied the truncations of bovine betaA3- and betaA1 crystallin in more detail. These proteins are identical except for the length of their N-terminal extension, 30 and 13 residues, respectively. The water-soluble and -insoluble proteins from cortex and nucleus of bovine lenses of different ages were separated by 2D-gel electrophoresis and immuno-blotted with an antiserum against betaA3. Two major truncation products were detected, which by sequence analysis were found to correspond to betaA3 having lost 11 or 22 amino acids. betaA3(-11) was only observed in the nucleus, whereas betaA3(-22) was present both in cortex and nucleus. We argue, therefore, that each of these two products is produced by a separate proteolytic enzyme. betaA3(-22) can originate by cleavage of betaA3, betaA1 and betaA3(-11). Truncation of betaA3 occurs more readily than that of betaA1, while betaA3(-11) disappears at an intermediate rate. It appears that the longer the N-terminal extension, the easier proteolysis takes place. Truncated proteins are not necessarily prone to end up in the water insoluble fractions; other modifications leading to charge changes are more likely to be responsible for insolubilization. Truncation of the extensions of beta-crystallins could be a functional rather than a harmful process during aging of the lens; by modulating protein repulsion, it may help to maintain the protein concentration gradient that is necessary for the optical quality of the lens. PMID- 9986748 TI - Interactions of spatial and luminance information in the retina of chickens during myopia development. AB - Degrading the retinal image by frosted eye occluders produces elongated eyes and 'deprivation myopia' in a variety of animal models. The postulated retinal 'deprivation detector' is quite sensitive to even small changes in image contrast or spatial frequency composition. Because psychophysical experiments have shown that a decline in luminance shifts the contrast sensitivity function to lower spatial frequencies, it is likely that only a reduced spatial frequency range is available for image analysis to control eye growth. It is even possible that the compression might be sufficient to promote deprivation myopia. We have tested this hypothesis, using the animal model of the chicken. (1) At an ambient illumination of 550 lux (about 76 cd m-2), neutral density (ND) filters placed in front of the eye with 0.0, 0.5 or 1.0 log unit attenuation did not change refractive development. However, monocularly or binocularly attached filters with 2 log units attenuation produced 5-7 D of myopia relative to normal eyes. Black occluders were not more effective. Frosted eye occluders with little effect on image brightness (about 0.5 log units attenuation) produced much more myopia (about 16 D compared with the controls). (2) The effects of the ND filters on refractive development could not be reproduced if the ambient illumination was reduced by 2 log units. Probably, minor effects on image quality were introduced by optical imperfections of the ND filters which were more critical at low retinal image brightness. (3) In an optomotor experiment (spatial frequency 0.2 cyc deg-1, stripe speed 57 deg sec-1), it was shown that the chickens' contrast sensitivity was severely reduced when the eyes were covered by 2.0 ND filters. (4) Since there is evidence that changes in dopamine release from the retina may be one of the factors affecting the development of myopia, we have tested how selective these changes were for spatial information. It was found that dopamine release was controlled by both spatial and luminance information and that the inputs of both could be scarcely separated. (5) Because the experiments show that the eye becomes more sensitive to image degradation at low light, the human eye may also be more prone to develop myopia if the light levels are low during extended periods of near work. PMID- 9986750 TI - Ex vivo human corneal epithelial cells express membrane-bound precursor and mature soluble epidermal growth factor (EGF) and transforming growth factor (TGF) alpha proteins. PMID- 9986749 TI - Protection from oxidative insult in glutathione depleted lens epithelial cells. AB - It has previously been shown that TEMPOL, n-propyl gallate and deferoxamine, compounds that limit the availability of Fe+2 and prevent the generation of hydroxyl radicals, protect cultured rabbit lens epithelial cells from H2O2 induced damage. In view of the importance of glutathione as an antioxidant and the decrease in GSH that is known to accompany most forms of cataract, we investigated whether these compounds protected cultured lens epithelial cells from H2O2 when the cells were artificially depleted of glutathione. Treatment of lens epithelial cells with 1-chloro-2,4-dinitrobenzene (CDNB), a compound that irreversibly binds to glutathione, or buthionine sulfoximine (BSO), an inhibitor of glutathione biosynthesis, reduced the glutathione content to an average of 15 20% of the control values without a concomitant increase in oxidized glutathione. Morphological changes were assessed by phase contrast and electron microscopy. In order to assess growth, cells in 5 ml serum-free MEM were exposed to an initial concentration of 0. 05 mm H2O2 (for 50,000 cells) or 2 doses of 0.5 mm H2O2 (for 800,000 cells). After exposure to H2O2, medium was replaced with MEM plus 8% rabbit serum; cells were fed on days 3 and 6 and counted on day 7. When 50,000 or 800,000 cells with decreased glutathione were exposed to 0.05 or 0.5 mm H2O2 the H2O2 was cytotoxic, whereas cells treated with H2O2 alone remained viable but showed inhibited proliferation. An unexpected finding was that cells continued to remove H2O2 from the medium at normal rates even when the GSH level was reduced. Cells treated with CDNB or BSO alone exhibited morphological and growth properties comparable to untreated cells. Cells treated with CDNB or BSO and then with H2O2 exhibited decreased cell-to-cell contact, nuclear shrinkage, and arborization when viewed with phase-contrast microscopy and showed extensive nuclear and cytoplasmic degeneration at the EM level. Cell death was determined by dye exclusion and confirmed by video microscopy. When cells were treated with CDNB or BSO and subsequently treated with TEMPOL, n-propyl gallate or deferoxamine and then challenged with H2O2 cytotoxicity was prevented and the cells were capable of growth. The data show that H2O2 was not lethal to glutathione-depleted lens epithelial cells when they were treated with compounds that prevented the generation of reactive oxygen species. In addition, the results indicate that GSH has an important protective role independent of its ability to decompose H2O2 via glutathione peroxidase. PMID- 9986751 TI - Image restrained modeling of alphaB-crystallin. PMID- 9986752 TI - Characterization of the minimal osmotic response element of the bovine Na+/myo inositol cotransporter gene. PMID- 9986753 TI - Erratum AB - It is regretted that a printer's error occurred during publication of this paper. The above title is correct. Copyright 1999 Academic Press. PMID- 9986754 TI - Announcements PMID- 9986755 TI - Dielectric resonator-based flow and stopped-flow EPR with rapid field scanning: A methodology for increasing kinetic information. AB - We report methodology which combines recently developed dielectric resonator based, rapid-mix, stopped-flow EPR (appropriate for small, aqueous, lossy samples) with rapid scanning of the external (Zeeman) magnetic field where the scanning is preprogrammed to occur at selected times after the start of flow. This methodology gave spectroscopic information complementary to that obtained by stopped-flow EPR at single fields, and with low reactant usage, it yielded more graphic insight into the time evolution of radical and spin-labeled species. We first used the ascorbyl radical as a test system where rapid scans triggered after flow was stopped provided "snapshots" of simultaneously evolving and interacting radical species. We monitored ascorbyl radical populations either as brought on by biologically damaging peroxynitrite oxidant or as chemically and kinetically interacting with a spectroscopically overlapping nitroxide radical. In a different biophysical application, where a spin-label lineshape reflected rapidly changing molecular dynamics of folding spin-labeled protein, rapid scan spectra were taken during flow with different flow rates and correspondingly different times after the mixing-induced inception of protein folding. This flow/rapid scan method is a means for monitoring early immobilization of the spin probe in the course of the folding process. PMID- 9986756 TI - Analysis of J coupling-induced fat suppression in DIET imaging. AB - The DIET (or dual interval echo train) sequence, a modification of the fast spin echo (FSE) sequence that selectively reduces signal from fat in MR images, has been investigated. The DIET sequence uses an initial echo spacing longer than that of a conventional FSE sequence, thus allowing J coupling-induced dephasing to take effect. The sequence is evaluated theoretically, and its effectiveness on a hydrocarbon (1-pentene) is demonstrated numerically using density matrix calculations. The sequence is also evaluated experimentally using in vitro solutions and in vivo imaging. The efficacy of the sequence is compared for different lipid chemical structures, field strengths, and pulse sequence parameters. PMID- 9986757 TI - Dead time-dependent line distortions in absolute-value electron spin echo envelope modulation spectra. AB - It is shown that in pulse EPR experiments, absolute-value spectra can be distorted because of the instrumental dead time to an extent that the interpretation of the spectral features becomes impossible. The mathematical background for the description of the distortions is given, and the far-reaching consequences of the effect are illustrated by model calculations. A cross-term averaging procedure is proposed to get rid of these distortions in two-, three-, and four-pulse electron spin echo envelope modulation experiments. The potential of cross-term averaging is demonstrated in two- and three-pulse experiments on a single crystal and a powder sample. PMID- 9986758 TI - SPRITE MRI with prepared magnetization and centric k-space sampling AB - A technique for imaging materials with short transverse relaxation times and prepared longitudinal magnetization is proposed. The technique is single-point ramped imaging with T1-enhancement (SPRITE) MRI with centric k-space sampling. The effects of transient state behavior on image resolution and signal/noise are estimated. Centric sampling in the basic SPRITE sequence gives increased signal to-noise and permits a quantitative determination of the MR parameters associated with longitudinal spin preparation. Spin-lock and inversion recovery preparation experiments are presented. Copyright 1999 Academic Press. PMID- 9986759 TI - Quantitative measurement of transverse and longitudinal cross-correlation between 13C-1H dipolar interaction and 13C chemical shift anisotropy: application to a 13C-labeled DNA duplex. AB - Measurement of both longitudinal and transverse relaxation interference (cross correlation) between 13C chemical shift anisotropy and 13C-1H dipolar interactions is described. The ratio of the transverse to longitudinal cross correlation rates readily yields the ratio of spectral densities J(0)/J(omegaC), independent of any structural attributes such as internuclear distance or chemical shift tensor. The spectral density at zero frequency J(0) is also independent of chemical exchange effects. With limited internal motions, the ratio also enables an accurate evaluation of the correlation time for overall molecular tumbling. Applicability of this approach to investigating dynamics has been demonstrated by measurements made at three temperatures using a DNA decamer duplex with purines randomly enriched to 15% in 13C. PMID- 9986760 TI - Modeling EPR powder spectra using numerical diagonalization of the spin hamiltonian AB - A new modeling code, ZFSFIT (standing for Zero Field Splitting FITting), written in FORTRAN 77 is proposed. It is designed for computing and fitting EPR powder spectra described by any spin Hamiltonian including second- and fourth-order ZFS terms (S A(0(+)u). AB - Laser excitation spectra of the lowest vibrational levels, v" = 2-5 and v' = 0-4, for the Bi2 X1Sigma+g --> A(0(+)u) system have been recorded for a wide range of rotational levels, 0 < J < 211, at Doppler-limited resolution of 0.013 cm-1. New rotational term values and spectroscopic constants are reported, improving the accuracy of predicted line positions for high rotational levels by as much as 0.8 cm-1. In addition, Franck-Condon factors are computed and compared with experimental observations from CW laser-induced fluorescence spectra. PMID- 9986769 TI - Potential Energy Curves and Electronic Structure of Copper Nitrides CuN and CuN+ Versus CuO and CuO+ AB - Ab initio configuration interaction calculations for the diatomic CuO, CuN, CuO+, and CuN+ have been carried out, and potential energy curves are reported for several low-lying states of these systems. The electronic structure and bonding, not yet known for the neutral copper nitride and its cation, are examined and compared to those of the copper oxide systems. We find that the ground states of these systems are X2Pi (CuO), X3Sigma- (CuN), X3Sigma- (CuO+), and X4Sigma- (CuN+); their first low-lying excited states Y2Sigma+, 1Delta, 1Delta, and 2Pi are located at 0.69, 1.45, 2.32, and 2.09 eV, respectively. For CuO we found two unobserved quartet states, namely 4Sigma- (Te = 1.09 eV) and 4Pi (Te = 1.86 eV). We report equilibrium structural parameters for various electronic states of the studied systems and compare them with experimental values, where it is possible. Copyright 1999 Academic Press. PMID- 9986770 TI - Dipole Moment Function of LiF and LiCl Obtained from the Herman-Wallis Analysis: A Comparative Study with the MBER Data. AB - FTIR absorption spectra of the fundamental bands of LiF and LiCl were measured with an apodized resolution of 0.01 cm-1. The Herman-Wallis analysis of these spectra led to the determination of the ratio of the dipole derivative to the permanent dipole moment, [ue/(du/dr)ere], for each molecule. The vibrational dependence of the dipole moment for each molecule has been already reported and these data were reanalyzed to determine the dipole moment function independently. The results from the Herman-Wallis analysis were compared with these results, and good agreement was found. This demonstrates that the Herman-Wallis analysis can produce reliable relative values of dipole moment functions. Copyright 1999 Academic Press. PMID- 9986771 TI - Diode-Laser Spectra of 13C32S2: The nu3 Band. AB - By diode-laser spectroscopy, spectra have been recorded for isotopically enriched carbon disulfide 13C32S2 in the region of the nu3 band near 1500 cm-1. The data were fitted and new molecular constants were determined. We also observed bands of isotopomers 13C32S33S and 13C32S34S. Copyright 1999 Academic Press. PMID- 9986772 TI - Analysis of Line Positions and Strengths of H216O Ground and Hot Bands Connecting to Interacting Upper States: (020), (100), and (001). AB - High-resolution spectra of H216O were recorded with a Fourier-transform spectrometer covering transitions in the (020)-(010), (100)-(010), and (001) (010) bands from 1100 to over 2300 cm-1. Also included in the study were previously reported measurements of these bands and measurements of the (020) (000), (100)-(000), and (001)-(000) bands from 2620 cm-1 to 4500 cm-1. The linestrengths were fitted to a model which takes into account the interactions between the vibrational states (020), (100), and (001). The model included dipole moment matrix elements (also referred to as transition elements) represented by 19 expansion coefficients for B-type transitions and 14 expansion coefficients for A-type band transitions. The most satisfactory results were obtained when the relative signs and values of the leading dipole moment terms of each of the three "hot" bands were as follows: u(020-010) = 1.936(97) x 10(-1) D, u(100-010) = 3.876(19) x 10(-2) D, and u(001-010) = 2.523(75) x 10(-2) D. Hot water emission experimental frequencies from other studies were included in an analysis to obtain rotational energies for levels up to high J and/or Ka of the (020), (100), and (001) vibrational states. The results from this study provide a more accurate representation of the parameters than those available at present for the six bands. Copyright 1999 Academic Press. PMID- 9986773 TI - The Overtone Spectrum of H2 32S near 13 200 cm-1. AB - The intracavity laser absorption spectrum of H2 32S has been recorded near 13 200 cm-1 with an equivalent absorption pathlength of 25 km. The observed spectrum is assigned to the (50(+/-), v2 = 1) states constituting a local mode pair in strong H22-type interaction. The rovibrational analysis has allowed the assignment of 210 lines involving 86 rotational upper state levels which have been reproduced with a rms of 0.023 cm-1 close to the experimental accuracy. A perturbation affecting one line is assigned to a local interaction with the (40(+/-), v2 = 3) local mode pair. The influence of the bending excitation on the local mode character of the (n0(+/-), v2 = 1) stretch-bend combination levels is discussed on the basis of the values of the rotational constants and of the H22 interaction parameters. Copyright 1999 Academic Press. PMID- 9986774 TI - Observation of the nuCH Excited Vibrational Levels in the A1A" State of HCP by IR UV Double Resonance Spectroscopy. AB - Rovibrational levels with one quantum of CH stretch mode, (1, v2, v3), in the A1A" electronic state of HCP were observed for the first time by IR-UV double resonance spectroscopy. Nine vibrational levels were identified in the energy region of 37 500-40 800 cm-1. Perturbations similar to those in the (0, v2, v3) levels were also observed in many of the vibrational levels. It was found that the CH stretch frequency in the A1A" state is reduced about 270 cm-1 relative to that of the electronic ground state. Copyright 1999 Academic Press. PMID- 9986775 TI - The D' left and right arrow A' Transition in ClF. AB - The D' (2 (3)P2) left and right arrow A'(2 (3)Pi) transition in ClF is studied in emission, in fluorescence, and through OODR excitation experiments. The emission spectrum is excited in a flowing Tesla discharge of ClF in half an atmosphere of Ar and is photographed at high resolution. The excitation and fluorescence spectra are obtained by pumping through perturbed levels of the B (0(+) 3Pi) valence state. The emission data yield a detailed characterization of v' levels 0 and 1 and v" levels 3-8. The excitation spectra extend the v' range to v' = 16 and put both states on an absolute energy scale. The low-resolution fluorescence spectra span v" = 1-17, the upper limit of which lies within approximately 20 cm 1 of dissociation. Key spectroscopic parameters (cm-1) from the study, valid for 35Cl19F, are: T'e = 55 253, omega'e = 365.22, omegaex'e = 2.005, T"e = 18 257, omega"e = 363.53, omegaex"e = 8.30, B'e = 0.21790, a'e = 0.00175, B"e = 0.33412, a"e = 0.00631, R'e = 2.5069 A, R"e = 2.024 A. A near-dissociation fit of the D' - > A' emission and fluorescence data locates the first dissociation limit at 21 495(5) cm-1, which is lower than the accepted value, but by just one standard error. Copyright 1999 Academic Press. PMID- 9986776 TI - Infrared Laser Spectroscopy of the nu4 and nu9 Band System of CH2F37Cl. AB - The spectra of CH2F37Cl (95% isotopically pure sample) have been recorded at high resolution with a tunable diode laser spectrometer in the regions 979-1030 and 1108-1136 cm-1. The spectral analysis allowed us to assign about 2000 lines (J 0, essentially by making a number of real coefficients complex, as required by the generalized internal-axis-method tunneling formalism. To reduce the number of adjustable parameters to an acceptable level in both the K = 0 and K = 1 effective Hamiltonians (used in separate K = 0 and K = 1 least-squares fits), a rather large number of assumptions concerning probably negligible parameters had to be made. The present fitting results should thus be considered as providing assurance of the group-theoretical line assignments as well as a nearly quantitative global interpretation of the tunneling splittings, even though they do not yet unambiguously determine the relative contributions from all 25 group theoretically inequivalent tunneling motions in this complex, nor do they permit quantitative extrapolation to higher K levels. Copyright 1999 Academic Press. PMID- 9986780 TI - Analysis of the nu8 + nu9 Band of HNO3, Line Positions and Intensities, and Resonances Involving the v6 = v7 = 1 Dark State. AB - Using a high-resolution (R = 0.0025 cm-1) Fourier transform spectrum of nitric acid recorded at room temperature in the 1100-1240 cm-1 region, it has been possible to perform a more extended analysis of the nu8 + nu9 band of HNO3 centered at 1205.7075 cm-1. As in a recent analysis of this band [W. F. Wang, P. P. Ong, T. L. Tan, E. C. Looi, and H. H. Teo, J. Mol. Spectrosc. 183, 407-413 (1997)], the Hamiltonian used for the line positions calculation takes into account, for the upper state, the DeltaK = +/-2 anharmonic resonance linking the rotational levels of the v8 = v9 = 1 "bright" vibrational state and those of the "dark" v6 = v7 = 1 vibrational state. More than 4800 lines were assigned in the nu8 + nu9 band, which involve significantly higher rotational quantum numbers than in previous works. On the other hand, and surprisingly as compared to previous studies, the nu8 + nu9 band appears to be a hybrid band. In fact, nonnegligible B-type transitions could be clearly identified among the much stronger A-type lines. Accordingly, a set of individual line intensities were measured for lines of both types and were introduced in a least-squares fit to get the A- and B-type components of the transition moment operator. Finally, a synthetic spectrum of the 8.3-um region of HNO3 has been generated, using for the line positions and line intensities the Hamiltonian constants and the expansion of the transition moment operator which were determined in this work. In this way, the B-type and the A-type components of the nu8 + nu9 band appear to contribute for about (1/4) and (3/4), respectively, to the total band intensity. Copyright 1999 Academic Press. PMID- 9986781 TI - Fourier Transform Emission Spectroscopy of the Visible Transitions of AuCl. AB - The visible electronic transitions of AuCl were observed at high resolution for the first time. The spectrum was recorded with the Fourier transform spectrometer associated with the McMath-Pierce solar telescope at Kitt Peak. The excited AuCl molecules were produced in a microwave discharge, with 4 Torr of helium seeded with 3% chlorine flowing over AuCl3 powder. Constants for the X1Sigma+, AOmega = 1, and BOmega = 0(+) states of Au35Cl are presented. The AOmega = 1 and the BOmega = 0(+) states may be two spin-orbit components of a 3Pi electronic state, and molecular parameters for this excited 3Pi state also are given. Copyright 1999 Academic Press. PMID- 9986782 TI - The Interacting v6 = 2 Levels of D3Si35Cl: A Tool to Determine Ground State Constants from High-Resolution Spectra in the 440-590 and 900-1100 cm-1 Regions. AB - High-resolution FTIR spectra of monoisotopic D3Si35Cl have been recorded in the regions 440-590 cm-1 (nu3/nu6) and 900-1100 cm-1 (2nu6/nu3 + nu6/2nu3). A detailed rovibrational study was done for the 2nu06, 2nu-/+26, and 2nu3 overtone bands and for the 2nu+/-26-nu+/-16, 2nu06-nu-/+16, and (nu3 + nu+/-16)-nu+/-16 hot bands. For the first time the interactions occurring between the v6 = 2, v3 = v6 = 1, and v3 = 2 levels of any trideuterated silyl halide have been analyzed. The (nu3 + nu+/-16)-nu+/-16 hot band served to obtain accurate energies of the v3 = v6 = 1 level, the nu3 + nu6 combination band not being detectable on our spectra. The first experimental determination of A0 and D0K for this molecule was undertaken by a well-established method, using the nu6, 2nu+/-26-nu+/-16, and 2nu /+26 bands. Ground state energy differences DeltaK(J) = E0(J, K) - E0(J, K - 3) were calculated for K values from 2 to 16. By a least-squares fit of 163 such differences, the A0 and D0K values thus obtained were (in cm-1): A0 = 1.4278230(8) and D0K = 5.3916(31) x 10(-6). Copyright 1999 Academic Press. PMID- 9986783 TI - High J Pure Inversion Spectrum of ND3 in the v2 = 1 State. PMID- 9986786 TI - Lindsay M. Black (1907-1997) PMID- 9986784 TI - Fitting Rovibrational Spectra of C3v Symmetric Top Molecules with Unitary Equivalent Parameter Sets: A Novel Application to the vt = 1 Level. PMID- 9986787 TI - Influenza virus inhibits cleavage of the HSP70 pre-mRNAs at the polyadenylation site. AB - Influenza virus infection is known to shut off the expression of host genes. To study the mechanism, we examined the effects of influenza A/Udorn/72 virus infection on the heat induction of a major heat shock protein, HSP70, in Madin Darby canine kidney cells. The induction of HSP70 protein synthesis was progressively suppressed with postinfection time when heat shock was applied. Northern hybridization analysis revealed the appearance of longer, heterogeneous HSP70 transcripts in the range of 2.7 to 30 kb with a concomitant decrease in the amount of the mature 2.7-kb mRNAs in the nucleus of the infected cells. Such longer beta-actin transcripts were also observed but with much less intensity. The longer HSP70 transcripts contained the downstream sequence of the polyadenylation site, as demonstrated by RNase protection with an antisense RNA probe containing the sequence through the polyadenylation sites. This clearly proved that influenza virus infection inhibits the polyadenylation-site cleavage of the pre-mRNAs by the host cleavage and polyadenylation machinery. One temperature-sensitive mutant virus carrying a temperature-sensitive mutation on the NS1 gene failed to inhibit the cleavage at the nonpermissive temperature, indicating that the NS1 protein is involved in the inhibition of the pre-mRNA cleavage. This is the first report of the down-regulation of cellular mRNA maturation at the point of polyadenylation-site cleavage by virus infection and identifies a new mechanism by which the influenza virus shuts off host gene expression. PMID- 9986788 TI - Transmission of human immunodeficiency type 1 viruses with intersubtype recombinant long terminal repeat sequences. AB - Retroviruses such as human immunodeficiency virus type 1 (HIV-1) contain two RNA strands per virion, and recombination can occur frequently during reverse transcription. Recombination may occur between HIV-1 genomes of the same subtype or among genomes of two or more distinct subtypes present in an individual. In the current study, we found that recombinatorial events were not limited to viral structural genes such as gag and env, but rather, recombination could likewise occur within the 5' long terminal repeat (LTR). Intersubtype recombinant LTRs among HIV-1 subtypes A, C, and D were found in Tanzanian infants. By introducing novel LTR sequences, these recombinant LTR viruses may further increase the adaptive potential and fitness of HIV-1. PMID- 9986789 TI - Subtype G and multiple forms of A/G intersubtype recombinant human immunodeficiency virus type 1 in Nigeria. AB - Multiple human immunodeficiency virus type 1 (HIV-1) genetic subtypes, intersubtype recombinants, and group O have been found in west central Africa. In Nigeria, where HIV-1 prevalence is rising rapidly, characterization of HIV-1 strains has been limited. Each of three full-length genome sequences acquired to date shows evidence of recombination: two are largely subtype G with subtype A segments in the midgenome accessory region; the third, IbNG, is subtype G with the long terminal repeats and two segments of pol from subtype A. In this study, peripheral blood mononuclear cells obtained in 1994-1995 from 10 patients hospitalized in northeastern Nigeria were evaluated by sequencing of the complete envelope and, from 7 patients, a portion of gag. Four patients harbored subtype G viruses and six patients had recombinant viruses. Two had strains sharing the A/G recombinant structure of IbNG. Two had a previously undescribed recombinant, mostly subtype A, whose carboxyl-terminal gp41 could not be classified. An A/G recombinant different from IbNG but similar to CA1, a Cameroonian strain, was found in one patient. The remaining patient had a strain that was otherwise subtype G but shared an unclassified carboxyl-terminal gp41 segment with the CA1 like strains. Other subtypes and group O were not found. PMID- 9986790 TI - Host range of human T-cell leukemia virus type I analyzed by a cell fusion dependent reporter gene activation assay. AB - We constructed a sensitive and quantitative assay system to examine human T-cell leukemia virus type I (HTLV-I) envelope (env) glycoprotein-mediated cell fusion in which T7 RNA polymerase in donor cells coexpressing env glycoproteins activates a reporter gene in recipient cells upon cell fusion. An efficient expression of HTLV-I env glycoproteins (gp46 and gp21) was observed in 293T cells transfected with an expression plasmid by both immunoblot and immunofluorescence analyses. The cells expressing env glycoproteins also exhibited self-fusion. By cocultivating the donor cells with recipient cells transfected with a reporter plasmid possessing the luciferase gene under the T7 promoter, the expression of luciferase was observed upon cell fusion. The activation of the luciferase gene was inhibited by either anti-env neutralizing antibody or synthetic peptide corresponding to env gp21, thus indicating the cell fusion to be specifically mediated by the HTLV-I env glycoproteins expressed in the donor cells. A broad range of cell lines exhibited susceptibility to HTLV-I env-mediated cell fusion by this assay. This newly established assay system may thus provide an efficient way both to study the fusion mechanisms mediated by HTLV-I env glycoproteins and to identify the HTLV-I receptor(s). PMID- 9986791 TI - A short region in the genome of hepatitis B virus is critical for maintenance of high transcript levels. AB - The majority of hepatitis B virus (HBV) transcripts are not normally spliced during the viral life cycle, but several splice donor and acceptor sites are conserved on HBV transcripts. In particular, the genome region between nt 450 and 500 of the HBV genome appears to be rich in such sequences. In this study we deleted a short 30-nt sequence between a conserved splice donor site at HBV genome position 462 and a splice acceptor site at position 491, thus deleting the surface/polymerase open reading frames by 10 amino acid residues. At the transcriptional level, this deletion led to >99% reduction of the 2.1-kb class of subgenomic transcripts in transfected cells. Nuclear run-on experiments revealed that the transcription rate of the deleted 2.1-kb transcript is unchanged when compared with the wildtype, suggesting a posttranscriptional mechanism for the downregulation of the deleted transcript. In addition, experiments with a replication-competent HBV mutant containing the 30-nt deletion showed that the corresponding 10-amino-acid sequence within the reverse transcriptase domain of the polymerase protein appeared to be nonessential. PMID- 9986792 TI - Characterization of conformation-dependent anti-gp120 murine monoclonal antibodies produced by immunization with monomeric and oligomeric human immunodeficiency virus type 1 envelope proteins. AB - Twenty-five conformation-dependent monoclonal antibodies (MAbs) produced by immunization of mice with oligomeric forms of the human immunodeficiency virus type 1 (HIV-1) envelope (env) glycoprotein were used to map exposed, immunogenic regions on oligomeric env. Based on MAb cross-competition, reactivity with diverse env proteins, and reactivity with a panel of gp120 mutants, seven distinct epitope clusters were identified. These include the classic CD4 binding site, V1/V2, and V3. in addition, several novel epitope clusters, including one mapping to the N- and C-termini of gp120, were identified. The locations of the seven epitope clusters on the gp120 core structure are proposed. PMID- 9986793 TI - Hepatitis A virus translation is rate-limiting for virus replication in MRC-5 cells. AB - Translation of hepatitis A virus (HAV) RNA is controlled by an internal ribosome entry site (IRES) located within the 5' untranslated region (UTR). In some cell types, the characteristically slow growth of HAV may be due to inefficient viral translation. We investigated whether this is true in MRC-5 cells, which are used for vaccine production. We measured the impact of two clusters of mutations in the 5' UTR on virus translation and replication: the AG group was selected during passage in African green monkey kidney cells, and the MR group was selected during subsequent passage in MRC-5 cells. The efficiency of cap-independent translation was assessed by inserting cDNA encoding an HAV IRES upstream of the chloramphenicol acetyl transferase gene and transcription was driven in vivo by a hybrid T7/vaccinia virus system. A luciferase gene was inserted upstream of the IRES to serve as an internal control. Each HAV UTR was also inserted into an infectious cDNA clone; the average rate of viral RNA accumulation was determined for each mutant virus. In MRC-5 cells, the rate of virus replication was highly correlated with the efficiency of cap-independent translation (P = 0.006). The MR but not the AG mutations significantly increased both translation and viral RNA accumulation. Reversion of just one MR mutation (687 G to A) eliminated all of the replication-stimulating and translation-enhancing effects of the MR mutations. In the control BS-C-1 cells, there was no discernible correlation between the rate of virus replication and the efficiency of cap-independent translation (P = 0.136): the AG and MR groups combined had a small impact on translation, but no detectable impact on virus replication. We conclude that in MRC-5 cells viral translation is rate-limiting for HAV replication. PMID- 9986794 TI - Sp1 is involved in a protein kinase C-independent activation of human T cell leukemia virus type I long terminal repeat by 12-O-tetradecanoylphorbol-13 acetate. AB - The long terminal repeat (LTR) of human T cell leukemia virus type-I (HTLV-I) contains binding sites for several cellular transcription factors that can activate its expression independently of the viral transactivator Tax protein. In a previous study, we have shown that 12-O-tetradecanoylphorbol-13-acetate (TPA) induces a Tax-independent activation of the viral LTR expression. We have also noted that although most other TPA biological effects are attributed to its protein kinase C (PKC)-activating potential, this particular effect of TPA is PKC independent and antagonized by PKC activity. In addition, we have demonstrated that deletion of the ets-responsive region 1 (ERR-1) from the LTR abolishes its response to TPA. In the present study, we demonstrate that TPA exerts this effect by enhancing the binding of the Sp1 transcription factor to an Sp1-binding site located within ERR-1. This Sp1-binding stimulation was not diminished by a potent PKC-specific inhibitor like bisindolylmaleimide-I, indicating that it did not depend on PKC activity. However, no increase in Sp1 protein level could be detected in the TPA-treated cells, suggesting that TPA exerted its effect by a posttranslational modification of Sp1 protein rather than by stimulating its synthesis. Although the proximal Tax responsive 21-bp element also contains an Sp1-binding site, the present study shows that the modified Sp1 protein mediates the TPA effect on LTR only through the Sp1 site of the ERR-1. PMID- 9986795 TI - An internal polypyrimidine-tract-binding protein-binding site in the hepatitis C virus RNA attenuates translation, which is relieved by the 3'-untranslated sequence. AB - Hepatitis C virus (HCV) RNA binds to several cellular proteins, which may regulate translation or replication of viral RNA. One of these is polypyrimidine tract-binding protein (PTB), which binds to the 5'-untranslated region (UTR) and the 3'-end 98 nucleotides (nt) (X region) of HCV RNA. Both of these PTB-binding sites regulate HCV translation. In this study, we further investigated the nature of PTB binding on HCV RNA. UV cross-linking studies using HeLa cell extracts and a recombinant PTB showed that the PTB-5'-UTR binding was much weaker than the PTB 3'-UTR binding. Unexpectedly, we found an even stronger PTB-binding site in the core-protein-coding region of HCV RNA. The binding domain was mapped to the 3' end of this region, which contains a pyrimidine-rich sequence highly conserved among HCV isolates. Using a set of synthetic HCV RNAs with or without this sequence in in vitro translation studies, we showed that the PTB-binding sequence in the core-coding region strongly inhibited translation of HCV RNA. This inhibition was relieved by the presence of the X region at the 3'-end. Furthermore, the previously reported translational enhancement by the HCV 3'-UTR was more pronounced when this PTB-binding site was present in the RNA. These results suggest that PTB binding to an internal site of HCV RNA provides another mechanism for regulation of HCV translation. PMID- 9986796 TI - Requirement for GP64 to drive efficient budding of Autographa californica multicapsid nucleopolyhedrovirus. AB - Budded virions (BV) of Autographa californica multicapsid nucleopolyhedrovirus (AcMNPV) contain a major envelope glycoprotein (GP64) that is present on the plasma membrane of infected cells. GP64 is acquired by virions during budding through the plasma membrane, the final step in assembly of the budded virion at the cell surface. Previous studies (S. A. Monsma, A. G. P. Oomens, and G. W. Blissard (1996). J. Virol. 70, 4607-4616) showed that insertional inactivation of the AcMNPV gp64 gene resulted in a virus unable to move from cell to cell and nonlethal to orally infected Trichoplusia ni larvae. To determine whether GP64 is involved in virion budding, we measured BV production from Sf9 cells infected with a gp64null virus. Sf9 cells infected with gp64null virus vAc64- were pulse labeled, and progeny BV were isolated on equilibrium sucrose gradients and quantified. BV production from vAc64- was reduced to approximately 2% of that from wild-type AcMNPV. Thus the GP64 protein is important for efficient virion budding. To determine whether the highly charged 7-amino acid cytoplasmic tail domain (CTD) of GP64 was required for virion production, we generated a series of GP64 constructs containing C-terminal truncations or substitutions. Modified forms of GP64 were analyzed in transfected cells and in recombinant viruses in which the wild-type gp64 gene was replaced with a modified gp64. Deletion of 1-7 amino acids from the CTD did not affect GP64 trimerization, protein transport to the cell surface, or membrane fusion activity. However, deletions of 11 or 14 amino acids, which removed the CTD and portions of the predicted transmembrane (TM) domain, were trimerized but were present at lower levels on the cell surface due to shedding of these truncated proteins. Comparisons of growth curves and quantitative measurements of labeled progeny BV production from recombinant viruses expressing either wild-type or mutant GP64 proteins showed that deletion of the 7-residue CTD only moderately reduced the production of infectious virions ( approximately 50%). However, deletions of the C terminal 11 or 14 amino acids had more substantial effects. Removal of the C terminal 11 amino acids reduced titers of infectious virus by 78-96% and labeled progeny virions were reduced by 91-92%. Removal of 14 amino acids from the C terminus resulted in an approximately 98% reduction in progeny BV and a virus that was apparently incapable of efficient propagation in cell culture. Thus the GP64 CTD is not essential for production of infectious BV, but removal of the CTD results in a measurable reduction in budding efficiency. Deletion of the CTD plus small portions of the transmembrane domain resulted in shedding of GP64, reduced surface levels, and a dramatic reduction in the production of BV. Together, these data indicate that GP64 is an important and limiting factor in BV production. PMID- 9986797 TI - Internal processing of hepatitis C virus NS3 protein. AB - Hepatitis C virus (HCV) NS3 protein contains at least three enzymatic activities: NS2-3 protease, NS3 serine protease, and NTPase/RNA helicase. It has been shown that NS2/3 cleavage is mediated by NS2-3 protease, whereas NS3 serine protease is responsible for the other four cleavage sites of the nonstructural (NS) region. In this study, we showed that the internal cleavage of NS3 protein produced two products of 49 kDa (NS3a) and 23 kDa (NS3b) when the entire NS3 region (aa 1027 1657) or the whole open reading frame (aa 1-3010) was expressed in mammalian and insect cells. By means of site-directed mutagenesis, we demonstrated that NS3a/NS3b cleavage occurs within the RNA helicase sequence motif that is highly conserved in the Flaviviridae family and that neither NS2-3 protease nor NS3 serine protease was responsible for this cleavage. The NS3 protease of flaviviruses, dengue virus type 2, for example, has been shown to mediate the internal cleavage of NS3. The NS3 proteins of HCV and dengue virus may thus be cleaved internally at the same sequence by different mechanisms of proteolysis. Also discussed is a possible role for the internal processing of HCV NS3 in the viral life cycle and its pathogenesis. PMID- 9986798 TI - Cis-acting functions of alfalfa mosaic virus proteins involved in replication and encapsidation of viral RNA. AB - cDNA clones of RNAs 1 and 2 of alfalfa mosaic virus (AMV) were slightly modified to permit transcription of infectious RNAs with T7 RNA polymerase. Together with transcripts of an available clone of AMV RNA 3, these transcripts were used to study cis- and trans-acting functions of AMV proteins in protoplasts from nontransgenic tobacco plants and from plants transformed with the P1 and P2 genes, encoded by RNAs 1 and 2, respectively. Transgenic P1 was unable to complement mutations in the P1 gene in RNA 1, pointing to a cis-acting function of P1 in RNA 1 replication. A study of the replication of RNA 3 mutants in nontransgenic protoplasts revealed that coat protein (CP) expressed from RNA 3 in the inoculum is required in trans for replication and encapsidation of RNAs 1 and 2 but is required in cis for replication and encapsidation of RNA 3. CP is required in the inoculum to initiate infection of nontransgenic plants and protoplasts. When protoplasts expressing both P1 and P2 (P12 protoplasts) were infected with RNAs 1, 2, and 3, initiation of replication of RNAs 1 and 2 required the presence of CP in the inoculum, whereas the initiation of replication of RNA 3 did not. This demonstrated that CP expressed from RNA 3 cannot substitute for the early function of CP in the inoculum. The results showed that CP in the inoculum is required to permit viral minus-strand RNA synthesis, whereas CP expressed from RNA 3 after the initiation of infection is required for plus-strand RNA synthesis. PMID- 9986799 TI - Safe determination of susceptibility of Mycobacterium tuberculosis to antimycobacterial agents by flow cytometry. AB - We showed previously that susceptibility testing for Mycobacterium tuberculosis labeled with fluorescein diacetate could be accomplished rapidly by using flow cytometry. However, safety was a major concern because mycobacteria were not killed prior to flow cytometric analysis. In this study, we developed a biologically safe flow cytometric susceptibility test that depends on detection and enumeration of actively growing M. tuberculosis organisms in drug-free and antimycobacterial agent-containing medium. The susceptibilities of 17 clinical isolates of M. tuberculosis to ethambutol, isoniazid, and rifampin were tested by the agar proportion and flow cytometric methods. Subsequently, all flow cytometric susceptibility test samples were inactivated by exposure to paraformaldehyde before analysis with a flow cytometer. Agreement between the results from the two methods was 98%. In addition, the flow cytometric results were available 72 h after the initiation of testing. The flow cytometric susceptibility assay is safe, simple to perform, and more rapid than conventional test methods, such as the BACTEC system and the proportion method. PMID- 9986800 TI - Prospective comparison of whole-blood- and plasma-based hepatitis C virus RNA detection systems: improved detection using whole blood as the source of viral RNA. AB - We previously demonstrated that whole blood contains significantly more hepatitis C virus (HCV) RNA than plasma. To validate the whole-blood-based HCV RNA detection method, a prospective comparison of HCV RNA detection in whole blood and plasma from 50 patients with chronic liver disease was undertaken. Whole blood and plasma aliquots were independently tested for HCV RNA by reverse transcriptase (RT) PCR assay, and plasma was tested by the Roche Amplicor assay. HCV RNA was detected in 35 of 50 (70%) whole-blood samples by RT-PCR but in only 26 of 50 (52%) plasma samples tested by the Amplicor assay (P < 0.01). HCV RNA was detected in 85% of HCV antibody-positive patients by the whole-blood method compared with 74% of plasma samples by the Amplicor method. The five HCV antibody positive subjects who were negative by whole-blood-based RT-PCR assay were all receiving interferon therapy and had normal transaminases at the time of testing. HCV RNA was detected in 38% of HCV antibody-negative subjects by the whole-blood based RT-PCR assay compared with 6.25% of these patients by the Amplicor assay (P < 0. 05). There were nine samples in which HCV RNA was detected in whole blood but the Amplicor test was negative. Eight of the nine RNAs prepared from these whole-blood samples tested positive in the Amplicor assay, thus confirming the specificity of our results. This study demonstrates that whole-blood-based HCV RNA detection is more sensitive than currently available commercial tests and that whole-blood RNA is suitable for use in commercial assays. PMID- 9986801 TI - Detection and quantitation of human papillomavirus by using the fluorescent 5' exonuclease assay. AB - A method for the detection and quantitation of oncogenic human papillomavirus (HPV) was developed by using the fluorescent 5' exonuclease assay. The method is based on the amplification of a 180-bp fragment from the 3' part of the E1 open reading frame in a single PCR with type-specific probes for HPV types 16, 18, 31, 33, and 35. The probes can be used separately or in combinations of up to three probes per assay. Quantitation over a range of 10(1) to 10(6) initial HPV copies was possible by using real-time detection of the accumulation of fluorescence with cycle number. Reconstitution experiments, performed to mimic mixed infections, showed that individual HPV types can be detected down to a ratio of about 1% in a mixture. The performance of the assay depends on DNA quality, the presence of PCR inhibitors, and the number of different probes used simultaneously. This homogeneous assay provides a fast and sensitive way of screening for oncogenic HPV types in biopsy specimens as well as cervical smear samples. The closed-tube nature of the assay and the inclusion of uracil N' glycosylase reduces cross contamination of PCR products to a minimum. A similar assay for beta-actin was used in parallel for quantitation of genomic DNA. After normalizing the samples for genomic DNA content, the mean number of HPV copies per cell could be calculated. PMID- 9986802 TI - Associations between virulence factors of Shiga toxin-producing Escherichia coli and disease in humans. AB - Associations between known or putative virulence factors of Shiga toxin-producing Escherichia coli and disease in humans were investigated. Univariate analysis and multivariate logistic regression analysis of a set of 237 isolates from 118 serotypes showed significant associations between the presence of genes for intimin (eae) and Shiga toxin 2 (stx2) and isolates from serotypes reported in humans. Similar associations were found with isolates from serotypes reported in hemorrhagic colitis and hemolytic-uremic syndrome. The enterohemorrhagic E. coli (EHEC) hemolysin gene was significantly associated with isolates from serotypes found in severe diseases in univariate analysis but not in multivariate logistic regression models. A strong association between the intimin and EHEC-hemolysin genes may explain the lack of statistical significance of EHEC hemolysin in these multivariate models, but a true lack of biological significance of the hemolysin in humans or in disease cannot be excluded. This result warrants further investigations of this topic. Multivariate analysis revealed an interaction between the eae and stx2 genes, thus supporting the hypothesis of the synergism between the adhesin intimin and Shiga toxin 2. A strong statistical association was observed between the stx2 gene and severity of disease for a set of 112 human isolates from eight major serotypes. A comparison of 77 isolates of bovine origin and 91 human isolates belonging to six major serotypes showed significant associations of the genes for Shiga toxin 1 and EspP protease with bovine isolates and an increased adherence on HEp-2 cell cultures for human isolates, particularly from diarrheic patients and healthy persons. PMID- 9986803 TI - Dissemination of two methicillin-resistant Staphylococcus aureus clones exhibiting negative staphylase reactions in intensive care units. AB - From December 1997 to March 1998, 25 methicillin-resistant Staphylococcus aureus (MRSA) isolates exhibiting negative Staphylase (Oxoid Ltd., Basingstoke, England) reactions were identified from various clinical specimens from 13 patients in six intensive care units (ICUs) or in wards following a stay in an ICU at the National Taiwan University Hospital. The characteristics of these isolates have not been previously noted in other MRSA isolates from this hospital. Colonies of all these isolates were grown on Trypticase soy agar supplemented with 5% sheep blood and were nonhemolytic and unpigmented. Seven isolates, initially reported as Staphylococcus haemolyticus (5 isolates) and Staphylococcus epidermidis (2 isolates) by the routine identification scheme and with the Vitek GPI system (bioMerieux Vitek, Inc., Hazelwood, Mo.), were subsequently identified as S. aureus by positive tube coagulase tests, standard biochemical reactions, and characteristic cellular fatty acid chromatograms. The antibiotypes obtained by the E test, coagulase types, restriction fragment length polymorphism profiles of the staphylococcal coagulase gene, and random amplified polymorphic DNA patterns generated by arbitrarily primed PCR of the isolates disclosed that two major clones disseminated in the ICUs. Clone 1 (16 isolates) was resistant to clindamycin and was susceptible to trimethoprim-sulfamethoxazole (TMP-SMZ) and was coagulase type II. Clone 2 (eight isolates) was resistant to clindamycin and TMP-SMZ and was coagulase type IV. These two epidemic clones from ICUs are unique and underline the need for caution in identifying MRSA strains with colonial morphologies not of the typical type and with negative Staphylase reactions. PMID- 9986804 TI - Identification of the enteropathogens Campylobacter jejuni and Campylobacter coli based on the cadF virulence gene and its product. AB - Campylobacter jejuni and Campylobacter coli are common causes of gastroenteritis in humans. Infection with C. jejuni or C. coli is commonly acquired by eating undercooked chicken. The goal of this study was to develop specific detection assays for C. jejuni and C. coli isolates based on the cadF virulence gene and its product. The cadF gene from C. jejuni and C. coli encodes a 37-kDa outer membrane protein that promotes the binding of these pathogens to intestinal epithelial cells. A fragment of approximately 400 bp was amplified from 38 of 40 (95%) C. jejuni isolates and 5 of 6 (83.3%) C. coli isolates with primers designed to amplify an internal fragment of the cadF gene. PCR was then used to amplify Campylobacter DNA from store-bought chickens. A 400-bp band was amplified from 26 of the 27 chicken carcasses tested by the PCR-based assay. The CadF protein was detected in every C. jejuni and C. coli isolate tested, as judged by immunoblot analysis with a rabbit anti-C. jejuni 37-kDa serum. In addition, methanol-fixed samples of whole-cell C. jejuni and C. coli were detected with the rabbit anti-37-kDa serum by using an indirect-immunofluorescence microscopy assay. These findings indicate that the cadF gene and its product are conserved among C. jejuni and C. coli isolates and that a PCR assay based on the cadF gene may be useful for the detection of Campylobacter organisms in food products. PMID- 9986805 TI - Detection of viable Mycobacterium tuberculosis by reverse transcriptase-strand displacement amplification of mRNA. AB - Numerous assays have been described for the detection of DNA and rRNA sequences that are specific for the Mycobacterium tuberculosis complex. Although beneficial to initial diagnosis, such assays have proven unsuitable for monitoring therapeutic efficacy owing to the persistence of these nucleic acid targets long after conversion of smears and cultures to negative. However, prokaryotic mRNA has a typical half-life of only a few minutes and we have previously shown that the presence of mRNA is a good indicator of bacterial viability. The purpose of the present study was to develop a novel reverse transcriptase-strand displacement amplification system for the detection of M. tuberculosis alpha antigen (85B protein) mRNA and to demonstrate the use of this assay in assessing chemotherapeutic efficacy in patients with pulmonary tuberculosis. The assay was applied to sequential, noninduced sputum specimens collected from four patients: 10 of 11 samples (91%) collected prior to the start of therapy were positive for alpha-antigen mRNA, compared with 1 of 8 (13%), 2 of 8 (25%), 2 of 8 (25%), and 0 of 8 collected on days 2, 4, 7, and 14 of treatment, respectively. In contrast, 39 of 44 samples (89%) collected on or before day 14 were positive for alpha antigen DNA. The loss of detectable mRNA corresponded to a rapid drop over the first 4 days of treatment in the number of viable organisms present in each sputum sample, equivalent to a mean fall of 0.43 log10 CFU/ml/day. Analysis of mRNA is a potentially useful method for monitoring therapeutic efficacy and for rapid in vitro determination of drug susceptibility. PMID- 9986806 TI - Improved detection of rhinoviruses in clinical samples by using a newly developed nested reverse transcription-PCR assay. AB - This paper describes the development and evaluation of a new nested reverse transcription (RT)-PCR for the detection of rhinovirus in clinical samples. The nucleotide sequences of the 5' noncoding regions of 39 rhinoviruses were determined in order to map the most conserved subregions. We designed a set of rhinovirus-specific primers and probes directed to these subregions and developed a new nested RT-PCR. The new assay includes an optimal RNA extraction method and amplicon identification with probe hybridization to discriminate between rhinoviruses and the closely related enteroviruses. It proved to be highly sensitive and specific. When tested on a dilution series of cultured viruses, the new PCR protocol scored positive at 10- to 100-fold-higher dilutions than a previously used nested RT-PCR. When tested on a collection of clinical samples obtained from 1,070 acute respiratory disease patients who had consulted their general practitioners, the new assay demonstrated a rhinovirus in 24% of the specimens, including all culture-positive samples, whereas the previously used PCR assay or virus culture detected a rhinovirus in only 3.5 to 6% of the samples. This new assay should help determine the disease burden associated with rhinovirus infections. PMID- 9986807 TI - Trends in antifungal use and epidemiology of nosocomial yeast infections in a university hospital. AB - This report describes both the trends in antifungal use and the epidemiology of nosocomial yeast infections at the University of Iowa Hospitals and Clinics between fiscal year (FY) 1987-1988 and FY 1993-1994. Data were gathered retrospectively from patients' medical records and from computerized databases maintained by the Pharmacy, the Program of Hospital Epidemiology, and the Medical Records Department. After fluconazole was introduced, use of ketoconazole decreased dramatically but adjusted use of amphotericin B decreased only moderately. However, the proportion of patients receiving antifungal therapy who were treated with amphotericin B declined markedly. In FY 1993-1994, 26 patients of the gastrointestinal surgery service received fluconazole. Among these patients, fluconazole use was prophylactic in 16 (61%), empiric in 3 (12%), and directed to a documented fungal infection in 7 (27%). Rates of nosocomial yeast infection in the adult bone marrow transplant unit increased from 6.77/1,000 patient days in FY 1987-1988 to 10.18 in FY 1989-1990 and then decreased to 0 in FY 1992-1993. Rates of yeast infections increased threefold in the medical and surgical intensive care units, reaching rates in FY 1993-1994 of 6.95 and 5.25/1,000 patient days, respectively. The rate of bloodstream infections increased from 0.044/1,000 patient days to 0.098, and the incidence of catheter related urinary tract infections increased from 0.23/1,000 patient days to 0.68. Although the proportion of infections caused by yeast species other than Candida albicans did not increase consistently, C. glabrata became an important nosocomial pathogen. PMID- 9986808 TI - Comparative analysis and serovar-specific identification of multiple-banded antigen genes of Ureaplasma urealyticum biovar 1. AB - Ureaplasma urealyticum is a causative agent of nongonococcal urethritis and is implicated in the pathogenesis of several other diseases. The species is divided into 14 serovars and two biovars, of which biovar 1 is most commonly isolated from clinical specimens. Reported associations between individual serovars and diseases have been difficult to confirm because of practical difficulties with serotyping. The multiple-banded antigen (MBA) is the predominant U. urealyticum antigen recognized during infections in humans and probably has a significant role in virulence. The 5' end of the MBA gene is relatively conserved but contains biovar, and possibly serovar, specificity. The 5' ends of the MBA genes of standard strains of U. urealyticum biovar 1, consisting of serovars 1, 3, 6, and 14, were amplified, cloned into pUC19, and sequenced to identify serovar specific differences. The 5' end of the MBA gene sequence of serovar 3 was identical with the previously published sequence and differed by only three bases from that of serovar 14. Significant differences between the MBA gene sequences allowed biovar 1 to be divided into two subgroups, containing serovars 3/14 and serovars 1 and 6, respectively, using primers UMS-125-UMA269 and UMS-125-UMA269'. Serovars 1 and 6 were distinguished by restriction enzyme analysis of the amplicon and/or by PCR specific for serovar 6. These methods were used to identify and type U. urealyticum in 185 (46.3%) of 400 genital specimens from women. Biovar 1 was detected in 89.2% and biovar 2 in 18.3% of positive specimens. Of 165 specimens containing U. urealyticum biovar 1, 22.2% contained more than one serovar and 46.7, 46.1, and 25.5% contained serovars 1, 3/14, and 6, respectively. U. urealyticum was found in a significantly higher proportion of pregnant women than in sex workers and other women attending a sexually transmissible diseases clinic (P < 0.01). The methods described are relatively rapid, practicable, and specific for serotyping isolates and for direct detection and identification of individual serovars in clinical specimens containing U. urealyticum biovar 1. PMID- 9986809 TI - Comparison of agar dilution, disk diffusion, MicroScan, and Vitek antimicrobial susceptibility testing methods to broth microdilution for detection of fluoroquinolone-resistant isolates of the family Enterobacteriaceae. AB - Fluoroquinolone resistance appears to be increasing in many species of bacteria, particularly in those causing nosocomial infections. However, the accuracy of some antimicrobial susceptibility testing methods for detecting fluoroquinolone resistance remains uncertain. Therefore, we compared the accuracy of the results of agar dilution, disk diffusion, MicroScan Walk Away Neg Combo 15 conventional panels, and Vitek GNS-F7 cards to the accuracy of the results of the broth microdilution reference method for detection of ciprofloxacin and ofloxacin resistance in 195 clinical isolates of the family Enterobacteriaceae collected from six U.S. hospitals for a national surveillance project (Project ICARE [Intensive Care Antimicrobial Resistance Epidemiology]). For ciprofloxacin, very major error rates were 0% (disk diffusion and MicroScan), 0.9% (agar dilution), and 2.7% (Vitek), while major error rates ranged from 0% (agar dilution) to 3.7% (MicroScan and Vitek). Minor error rates ranged from 12.3% (agar dilution) to 20.5% (MicroScan). For ofloxacin, no very major errors were observed, and major errors were noted only with MicroScan (3.7% major error rate). Minor error rates ranged from 8.2% (agar dilution) to 18.5% (Vitek). Minor errors for all methods were substantially reduced when results with MICs within +/-1 dilution of the broth microdilution reference MIC were excluded from analysis. However, the high number of minor errors by all test systems remains a concern. PMID- 9986810 TI - The Borrelia burgdorferi 37-kilodalton immunoblot band (P37) used in serodiagnosis of early lyme disease is the flaA gene product. AB - The 37-kDa protein (P37) of Borrelia burgdorferi is an antigen that elicits an early immunoglobulin M (IgM) antibody response in Lyme disease patients. The P37 gene was cloned from a B. burgdorferi genomic library by screening with antibody from a Lyme disease patient who had developed a prominent humoral response to the P37 antigen. DNA sequence analysis of this clone revealed the identity of P37 to be FlaA, an outer sheath protein of the periplasmic flagella. Recombinant P37 expression was accomplished in Escherichia coli by using a gene construct with the leader peptide deleted and fused to a 38-kDa E. coli protein. The recombinant antigen was reactive in IgM immunoblots using serum samples from patients clinically diagnosed with early Lyme disease that had been scored positive for B. burgdorferi anti-P37 reactivity. Lyme disease patient samples serologically negative for the B. burgdorferi P37 protein did not react with the recombinant. Recombinant P37 may be a useful component of a set of defined antigens for the serodiagnosis of early Lyme disease. This protein can be utilized as a marker in diagnostic immunoblots, aiding in the standardization of the present generation of IgM serologic tests. PMID- 9986811 TI - Measurement of urinary lactoferrin as a marker of urinary tract infection. AB - The usefulness of the measurement of urinary lactoferrin (LF) released from polymorphonuclear leukocytes and of an immunochromatography test strip devised for measuring urinary LF for the simple and rapid diagnosis of urinary tract infections (UTI) was evaluated. Urine specimens were collected from apparently healthy persons and patients diagnosed as suffering from UTI. In the preliminary study, the LF concentrations in 121 normal specimens and 88 specimens from patients (60 with UTI) were quantified by an enzyme-linked immunosorbent assay. The LF concentration was 3,300.0 +/- 646.3 ng/ml (average +/- standard error of the mean) in the specimens from UTI patients, whereas it was 30.4 +/- 2.7 ng/ml and 60.3 +/- 14.9 ng/ml in the specimens from healthy persons and the patients without UTI, respectively. Based on these results, a 200-ng/ml LF concentration was chosen as the cutoff value for negativity. Each urine specimen was reexamined with the newly devised immunochromatography (IC) test strip to calculate the indices of efficacy. Based on the cutoff value, it was calculated that the sensitivity, specificity, and positive and negative predictive values of the IC test were 93.3, 89.3, 86.2, and 94.9%, respectively, compared with the results of the microscopic examination of the urine specimens for the presence of leukocytes. The respective indices for UTI were calculated as 95.0, 92.9, 89.7, and 96.6%. The tests were completed within 10 min. These results indicated that urine LF measurement with the IC test strip provides a useful tool for the simple and rapid diagnosis of UTI. PMID- 9986812 TI - Serologic testing for human granulocytic ehrlichiosis at a national referral center. AB - An indirect immunofluorescence assay (IFA) was used to identify patients with antibodies reactive to the human granulocytic ehrlichiosis (HGE) agent. Serum samples collected from clinically ill individuals were submitted to the Centers for Disease Control and Prevention by physicians via state health departments from throughout the United States and tested against a panel of ehrlichial and rickettsial pathogens. Antibodies reactive to the HGE agent were detected in 142 (8.9%) of 1,602 individuals tested. There were 19 confirmed and 59 probable (n = 78) cases of HGE as defined by seroconversion or a fourfold or higher titer to the HGE agent than to the Ehrlichia chaffeensis antigens. The average age of patients with HGE was 57 years, and males accounted for 53 (68%) of the patients. Cases of HGE occurred in 21 states; 47 (60%) of the cases occurred in Connecticut (n = 14), New York (n = 18), and Wisconsin (n = 15). Onset of HGE was identified from April through December, with cases peaking in June and July. The earliest confirmed cases of HGE occurred in 1987 in Wisconsin and 1988 in Florida. No fatalities were reported among the 78 patients with confirmed or probable HGE. Reactivity to the HGE agent and to either Coxiella burnetii, Rickettsia rickettsii, or Rickettsia typhi was infrequent; however, 74 (52%) of the 142 individuals who were positive for HGE had at least one serum sample that also reacted to the E. chaffeensis antigen. Thirty-four persons with confirmed or probable human monocytic ehrlichiosis due to E. chaffeensis also had antibodies to the HGE agent in at least one serum sample. The specific etiologic agent for 30 patients was not ascribed because of similarity of titers to both ehrlichial antigens. The use of both antigens may be required to correctly diagnose most cases of human ehrlichiosis, especially in geographic regions where both the HGE agent and E. chaffeensis occur. PMID- 9986813 TI - Genetic diversity of Borrelia burgdorferi in lyme disease patients as determined by culture versus direct PCR with clinical specimens. AB - Two hundred seventeen isolates of Borrelia burgdorferi originally cultured from skin biopsy samples or blood of early Lyme disease patients were genetically characterized by PCR-restriction fragment length polymorphism (RFLP) typing of the 16S-23S ribosomal DNA intergenic spacer. Three major RFLP types were observed. Of the cultured isolates, 63 of 217 (29.0%) were type 1, 85 of 217 (39.2%) were type 2, and 58 of 217 (26.7%) were type 3; mixtures of two RFLP types were obtained in 6.0% (13 of 217) of the cultures. Comparison of typing of B. burgdorferi performed directly on 51 patient skin specimens with typing of cultures originally isolated from the same tissue revealed that a much larger proportion of direct tissue samples had mixtures of RFLP types (43.1% by direct typing versus 5.9% by culture [P < 0.001). In addition, identical RFLP types were observed in only 35.5% (11 of 31) of the paired samples. RFLP type 3 organisms were recovered from blood at a significantly lower rate than were either type 1 or type 2 strains. These studies demonstrate that the genetic diversity of B. burgdorferi patient isolates as determined by cultivation differs from that assessed by PCR performed directly on patient tissue. PMID- 9986814 TI - Rapid identification and typing of Staphylococcus aureus by PCR-restriction fragment length polymorphism analysis of the aroA gene. AB - The Staphylococcus aureus aroA gene, which encodes 5-enolpyruvylshikimate-3 phosphate synthase, was used as a target for the amplification of a 1,153-bp DNA fragment by PCR with a pair of primers of 24 and 19 nucleotides. The PCR products, which were detected by agarose gel electrophoresis, were amplified from all S. aureus strains so far analyzed (reference strains and isolates from cows and sheep with mastitis, as well as 59 isolates from humans involved in four confirmed outbreaks). Hybridization with an internal 536-bp DNA fragment probe was positive for all PCR-positive samples. No PCR products were amplified when other Staphylococcus spp. or genera were analyzed by using the same pair of primers. The detection limit for S. aureus cells was 20 CFU when the cells were suspended in saline; however, the sensitivity of the PCR was lower (5 x 10(2) CFU) when S. aureus cells were suspended in sterilized whole milk. TaqI digestion of the PCR-generated products rendered two different restriction fragment length polymorphism patterns with the cow and sheep strains tested, and these patterns corresponded to the two different patterns obtained by antibiotic susceptibility tests. Analysis of the 59 human isolates by our easy and rapid protocol rendered results similar to those of other assays. PMID- 9986815 TI - Rapid detection of the Chlamydiaceae and other families in the order Chlamydiales: three PCR tests. AB - Few identification methods will rapidly or specifically detect all bacteria in the order Chlamydiales, family Chlamydiaceae. In this study, three PCR tests based on sequence data from over 48 chlamydial strains were developed for identification of these bacteria. Two tests exclusively recognized the Chlamydiaceae: a multiplex test targeting the ompA gene and the rRNA intergenic spacer and a TaqMan test targeting the 23S ribosomal DNA. The multiplex test was able to detect as few as 200 inclusion-forming units (IFU), while the TaqMan test could detect 2 IFU. The amplicons produced in these tests ranged from 132 to 320 bp in length. The third test, targeting the 23S rRNA gene, produced a 600-bp amplicon from strains belonging to several families in the order Chlamydiales. Direct sequence analysis of this amplicon has facilitated the identification of new chlamydial strains. These three tests permit ready identification of chlamydiae for diagnostic and epidemiologic study. The specificity of these tests indicates that they might also be used to identify chlamydiae without culture or isolation. PMID- 9986816 TI - Genetic diversity and population structure of Vibrio cholerae. AB - Multilocus enzyme electrophoresis (MLEE) of 397 Vibrio cholerae isolates, including 143 serogroup reference strains and 244 strains from Mexico and Guatemala, identified 279 electrophoretic types (ETs) distributed in two major divisions (I and II). Linkage disequilibrium was demonstrated in both divisions and in subdivision Ic of division I but not in subdivision Ia, which includes 76% of the ETs. Despite this evidence of relatively frequent recombination, clonal lineages may persist for periods of time measured in at least decades. In addition to the pandemic clones of serogroups O1 and O139, which form a tight cluster of four ETs in subdivision Ia, MLEE analysis identified numerous apparent clonal lineages of non-O1 strains with intercontinental distributions. A clone of serogroup O37 that demonstrated epidemic potential in the 1960s is closely related to the pandemic O1/O139 clones, but the nontoxigenic O1 Inaba El Tor reference strain is not. A strain of serogroup O22, which has been identified as the most likely donor of exogenous rfb region DNA to the O1 progenitor of the O139 clone, is distantly related to the O1/O139 clones. The close evolutionary relationships of the O1, O139, and O37 epidemic clones indicates that new cholera clones are likely to arise by the modification of a lineage that is already epidemic or is closely related to such a clone. PMID- 9986817 TI - Multicenter comparison of the sensititre YeastOne Colorimetric Antifungal Panel with the National Committee for Clinical Laboratory standards M27-A reference method for testing clinical isolates of common and emerging Candida spp., Cryptococcus spp., and other yeasts and yeast-like organisms. AB - National Committee for Clinical Laboratory Standards (NCCLS) standard guidelines are available for the antifungal susceptibility testing of common Candida spp. and Cryptococcus neoformans, but NCCLS methods may not be the most efficient and convenient procedures for use in the clinical laboratory. MICs of amphotericin B, fluconazole, flucytosine, itraconazole, and ketoconazole were determined by the commercially prepared Sensititre YeastOne Colorimetric Antifungal Panel and by the NCCLS M27-A broth microdilution method for 1,176 clinical isolates of yeasts and yeast-like organisms, including Blastoschizomyces capitatus, Cryptococcus spp., 14 common and emerging species of Candida, Hansenula anomala, Rhodotorula spp., Saccharomyces cerevisiae, Sporobolomyces salmonicolor, and Trichosporon beigelii. Colorimetric MICs of amphotericin B corresponded to the first blue well (no growth), and MICs of the other agents corresponded to the first purple or blue well. Three comparisons of MIC pairs by the two methods were evaluated to obtain percentages of agreement: 24- and 48-h MICs and 24-h colorimetric versus 48-h reference MICs. The best performance of the YeastOne panel was with 24-h MICs (92 to 100%) with the azoles and flucytosine for all the species tested, with the exception of C. albicans (87 to 90%). For amphotericin B, the best agreement between the methods was with 48-h MIC pairs (92 to 99%) for most of the species tested. The exception was for isolates of C. neoformans (76%). These data suggest the potential value of the YeastOne panel for use in the clinical laboratory. PMID- 9986818 TI - Body lice as tools for diagnosis and surveillance of reemerging diseases. AB - Body lice are vectors of three bacteria which cause human disease: Rickettsia prowazekii, the agent of epidemic typhus; Bartonella quintana, the agent of trench fever; and Borrelia recurrentis, the agent of relapsing fever. A recrudescence of body lice is being observed as the numbers of individuals living under social conditions which predispose individuals to infestation have increased. Because this phenomenon may lead to the reemergence of infections transmitted by body lice, we aimed to assess the occurrence and prevalence of the three agents described above in more than 600 body lice collected from infested individuals in the African countries of Congo, Zimbabwe, and Burundi, in France, in Russia, and in Peru. The presence of the three bacteria in each louse was determined by specific PCR amplification, and the identities of the organisms detected were confirmed by determination of the nucleotide base sequences of the amplification products. Using this approach, we were able to confirm the presence of R. prowazekii in lice collected from refugees in Burundi, among whom typhus was epidemic, and the presence of B. quintana in lice collected from all locations except the Congo. B. recurrentis was never found. Molecular approaches are convenient tools for the detection and identification of bacterial DNA in body lice and for the epidemiological study of louse-borne bacteria from countries where no medical and biological laboratory facilities are available. PMID- 9986819 TI - Typing of clinical Mycobacterium avium complex strains cultured during a 2-year period in Denmark by using IS1245. AB - In the present study restriction fragment length polymorphism analyses with the recently described insertion sequence IS1245 as a probe was performed with clinical Mycobacterium avium complex strains cultured in Denmark during a 2-year period. The overall aim of the study was to disclose potential routes of transmission of these microorganisms. As a first step, the genetic diversity among isolates from AIDS patients and non-human immunodeficiency virus (HIV) infected patients was described. In addition, a number of isolates from nonhuman sources cultured during the same period were analyzed and compared to the human isolates. A total of 203 isolates from AIDS patients (n = 90), non-HIV-infected patients (n = 91), and nonhuman sources (n = 22) were analyzed. The presence of IS1245 was restricted to Mycobacterium avium subsp. avium isolates. The majority of human isolates had large numbers of IS1245 copies, while nonhuman isolates could be divided into a high-copy-number group and a low-copy-number group. Groups of identical strains were found to be geographically widespread, comprising strains from AIDS patients as well as strains from non-HIV-infected patients. Samples of peat (to be used as potting soil) and veterinary samples were found to contain viable M. avium isolates belonging to genotypes also found in humans. PMID- 9986820 TI - Nested duplex PCR to detect Bordetella pertussis and Bordetella parapertussis and its application in diagnosis of pertussis in nonmetropolitan Southeast Queensland, Australia. AB - A duplex PCR to detect Bordetella pertussis and Bordetella parapertussis was developed with the insertion sequences IS481 (B. pertussis) and IS1001 (B. parapertussis) and evaluated with specimens from 520 consecutive patients presenting with possible pertussis. No culture-positive-PCR-negative results occurred, giving the method a sensitivity of 100%. For B. pertussis, 58 of 520 patients (11.2%) were positive by PCR compared to 17 of 520 patients positive (3.3%) by culture. For B. parapertussis, 7 of 520 patients (1.3%) were positive by PCR compared to 2 of 520 patients positive (0.4%) by culture. Two patients were positive for both B. pertussis and B. parapertussis. Patient records were reviewed to determine the validity of PCR-positive-culture-negative results. Forty-two of 49 patients who could be evaluated fulfilled the criteria for a case definition of pertussis, with 32 patients being <1 year of age and having classical pertussis symptoms. The seven patients who did not fulfil the criteria were aged 7 to 55 years and had a persistent cough for >2 weeks. The method was also used to investigate a classroom outbreak in which B. pertussis culture was positive for 5 of 28 patients. All five culture-positive specimens were confirmed by PCR, and an additional eight were positive by PCR. Of 25 patients from a suspected pertussis outbreak in a girls' dormitory, seven of seven specimens were negative for B. pertussis, although 13 of 25 patients were positive for B. pertussis immunoglobulin M (IgM) (2 of which produced equivocal IgA results, with 23 of 25 patients being negative). Five symptomatic patients were subsequently found to be positive (by IgM and particle agglutination assays) for Mycoplasma pneumoniae, demonstrating the value of PCR in rapidly excluding B. pertussis infection in an outbreak situation. Twenty-two of 71 (30. 1%) throat swabs were positive by PCR compared to 2 of 71 (2.8%) throat swabs positive by culture, indicating that a reassessment of the use of throat swabs should be considered, particularly for older patients, in contact tracing, and in situations in which specimen collection is difficult. PMID- 9986821 TI - TechLab and alexon Giardia enzyme-linked immunosorbent assay kits detect cyst wall protein 1. AB - A Giardia lamblia antigen detected by the TechLab Giardia Test (TechLab, Inc., Blacksburg, Va.) and the Alexon ProSpecT Giardia microplate assay (Alexon, Inc., Sunnyvale, Calif.) was purified by immunoaffinity chromatography from supernatant fluids of encystment cultures. Two major proteins (Mr 22,000 and 26,000) were observed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and Coomassie staining that did not resemble the GSA65 antigen reportedly detected by the Alexon test. These proteins reacted intensely with the monoclonal antibodies used in both commercial enzyme-linked immunosorbent assays (ELISAs). Both proteins had identical N-terminal amino acid sequences and were identified as cyst wall protein 1 (CWP1). The 26-kDa form appeared early during encystment followed by the appearance of the 22-kDa form. Recombinant CWP1 (Mr 26,000) was strongly positive in both commercial tests. CWP1 was stable in human stool specimens, resistant to degradation by proteases and N- and O-glycanases, and unaffected by oxidation with sodium periodate. Two minor proteins with Mrs of 32,000 and 39,000 were detected in CWP1 preparations by using a sensitive fluorescent protein stain. Both were identified as CWP2, and neither reacted with the monoclonal antibodies from the commercial tests. We analyzed 535 stool specimens for CWP1 by using both commercial ELISAs and resolved discrepant results by using routine ova and parasite examination (O&P) and on immunofluorescence antibody assay. The presence of CWP1 correlated well between both ELISAs (98.7% correlation). Our results demonstrate that both commercial ELISAs detect CWP1, which is a useful diagnostic marker because it is highly stable, is secreted in large amounts by encysting trophozoites, and correlates well with O&P. PMID- 9986822 TI - Improved silica-guanidiniumthiocyanate DNA isolation procedure based on selective binding of bovine alpha-casein to silica particles. AB - DNA purified from clinical cerebrospinal fluid and urine specimens by a silica guanidiniumthiocyanate procedure frequently contained an inhibitor(s) of DNA processing enzymes which may have been introduced by the purification procedure itself. Inhibition could be relieved by the use of a novel lysis buffer containing alpha-casein. When the novel lysis buffer was used, alpha-casein was bound by the silica particles in the first step of the procedure and eluted together with DNA in the last step, after which it exerted its beneficial effects for DNA-processing enzymes. In the present study we have compared the novel lysis buffer with the previously described lysis buffer with respect to double-stranded DNA yield (which was nearly 100%) and the performance of DNA-processing enzymes. PMID- 9986823 TI - Mycoplasma hyopneumoniae potentiation of porcine reproductive and respiratory syndrome virus-induced pneumonia. AB - An experimental model that demonstrates a mycoplasma species acting to potentiate a viral pneumonia was developed. Mycoplasma hyopneumoniae, which produces a chronic, lymphohistiocytic bronchopneumonia in pigs, was found to potentiate the severity and the duration of a virus-induced pneumonia in pigs. Pigs were inoculated with M. hyopneumoniae 21 days prior to, simultaneously with, or 10 days after inoculation with porcine reproductive and respiratory syndrome virus (PRRSV), which induces an acute interstitial pneumonia in pigs. PRRSV-induced clinical respiratory disease and macroscopic and microscopic pneumonic lesions were more severe and persistent in M. hyopneumoniae-infected pigs. At 28 or 38 days after PRRSV inoculation, M. hyopneumoniae-infected pigs still exhibited lesions typical of PRRSV-induced pneumonia, whereas the lungs of pigs which had received only PRRSV were essentially normal. On the basis of macroscopic lung lesions, it appears that PRRSV infection did not influence the severity of M. hyopneumoniae infection, although microscopic lesions typical of M. hyopneumoniae were more severe in PRRSV-infected pigs. These results indicate that M. hyopneumoniae infection potentiates PRRSV-induced disease and lesions. Most importantly, M. hyopneumoniae-infected pigs with minimal to nondetectable mycoplasmal pneumonia lesions manifested significantly increased PRRSV-induced pneumonia lesions compared to pigs infected with PRRSV only. This discovery is important with respect to the control of respiratory disease in pigs and has implications in elucidating the potential contribution of mycoplasmas in the pathogenesis of viral infections of other species, including humans. PMID- 9986824 TI - Application of pbp1A PCR in identification of penicillin-resistant Streptococcus pneumoniae. AB - A seminested PCR assay, based on the amplification of the pneumococcal pbp1A gene, was developed for the detection of penicillin resistance in clinical isolates of Streptococcus pneumoniae. The assay was able to differentiate between intermediate (MICs = 0.25 to 0.5 microgram/ml) and higher-level (MICs = >/=1 microgram/ml) resistance. Two species-specific primers, 1A-1 and 1A-2, which amplified a 1,043-bp region of the pbp1A penicillin-binding region, were used for pneumococcal detection. Two resistance primers, 1A-R1 and 1A-R2, were designed to bind to altered areas of the pbp1A gene which, together with the downstream primer 1A-2, amplify DNA from isolates with penicillin MICs of >/=0.25 and >/=1 microgram/ml, respectively. A total of 183 clinical isolates were tested with the pbp1A assay. For 98.3% (180 of 183) of these isolates, the PCR results obtained were in agreement with the MIC data. The positive and negative predictive values of the assay were 100 and 91%, respectively, for detecting strains for which the MICs were >/=0.25 microgram/ml and were both 100% for strains for which the MICs were >/=1 microgram/ml. PMID- 9986825 TI - Pneumolysin PCR-based diagnosis of invasive pneumococcal infection in children. AB - Blood-based pneumolysin PCR was compared to blood culture and detection of pneumolysin immune complexes, as well as to detection of antibodies to pneumolysin and to C polysaccharide, in the diagnosis of pneumococcal infection in 75 febrile children. Invasive pneumococcal infection was suspected on clinical grounds in 67 of the febrile children, and viral infection was suspected on clinical grounds in 8 of the febrile children. In addition, 15 healthy persons were examined to test the specificity of the PCR assay. Plasma, serum, and leukocyte fractions were analyzed by PCR. The combination of all test results led to the diagnosis of pneumococcal infection in 25 patients. Pneumolysin PCR was positive in 44% of these children, an increase occurred in the pneumolysin antibodies in 39% and in the C polysaccharide antibodies in 30% of the patients; pneumolysin immune complexes were found in convalescent serum in 30%, pneumolysin immune complexes occurred in acute-phase serum samples in 16%, and a positive blood culture was found in 20% of the patients. None of the healthy controls had positive results by PCR. The results suggest that the diagnosis of Streptococcus pneumoniae infection from blood samples necessitates the use of several different assays. Pneumolysin PCR was the most sensitive assay, but its clinical value is reduced by the fact that three blood fractions are needed. PMID- 9986826 TI - Molecular characterization of penicillin-resistant Streptococcus pneumoniae isolates from Bulgaria. AB - As part of an ongoing surveillance program of antibiotic-resistant Streptococcus pneumoniae in Sofia, Bulgaria, 120 penicillin-resistant strains (PRSP) (most of them recovered from children hospitalized with pneumococcal disease) were analyzed by microbiological and molecular methods. Several unique features of this collection are of particular interest. (i) Most isolates (112 of 120) were also resistant to trimethoprim-sulfamethoxazole (SXT) (97 of 120 isolates, or 80%), and over 70% (86 of 120) of the isolates were resistant to at least three antibiotics in addition to penicillin. (ii) Close to 80% of all isolates were represented by large clusters of bacteria, each with a unique serotype, antibiotype, and chromosomal macrorestriction pattern (determined by pulsed-field gel electrophoresis), as well as unique restriction fragmentation length polymorphisms of the penicillin-binding protein genes pbp1a, pbp2x, and pbp2b. (iii) A large proportion (45 of 120, or 38%) of the strains belonged to two internationally spread epidemic clones of S. pneumoniae, the first expressing capsular type 23F and the second expressing serotype 9. (iv) A unique Bulgarian cluster composed of eight serotype 19F isolates was resistant to tetracycline, SXT, cefotaxime, and extremely high levels of penicillin and erythromycin. Nevertheless, this clone did not react with either the erm or the mef DNA probes, and thus the mechanism of macrolide resistance in this group of PRSP remains to be elucidated. PMID- 9986827 TI - Laboratory diagnosis of Toscana virus infection by enzyme immunoassay with recombinant viral nucleoprotein. AB - A recombinant enzyme immunoassay (rEIA) to detect serum immunoglobulin M (IgM) and IgG to Toscana virus (TOSV) was developed with the aim of establishing a simple and easily available assay for diagnosing acute and/or previous infections. The rEIA, based on the recombinant nucleoprotein of TOSV expressed in Escherichia coli, was evaluated with 97 serum samples collected in an area where TOSV is endemic and compared to an analogous assay based on cell-derived TOSV. Discordant results were resolved by immunoblotting (IB). Twenty-two of these samples, obtained from subjects hospitalized during the summer season with meningitis of suspected TOSV etiology, were further characterized by indirect immunofluorescence and IB, and detection of specific TOSV RNA sequences in the cerebrospinal fluid of these patients was attempted by nested PCR. The results indicated that rEIA was able to diagnose acute TOSV infection by detection of specific serum IgM in all of the subjects with TOSV meningitis confirmed by nested PCR or serology. The overall sensitivity and specificity of rEIA were both 100% for IgM detection and 100 and 96.6%, respectively, for IgG detection. Thus, rEIA appears to be a simple and reliable laboratory test for the diagnosis of acute TOSV infection and for the assessment of immune status. PMID- 9986828 TI - Phylogenetic relationships of varieties and geographical groups of the human pathogenic fungus Histoplasma capsulatum Darling. AB - The phylogeny of 46 geographically diverse Histoplasma capsulatum isolates representing the three varieties capsulatum, duboisii, and farciminosum was evaluated using partial DNA sequences of four protein coding genes. Parsimony and distance analysis of the separate genes were generally congruent and analysis of the combined data identified six clades: (i) class 1 North American H. capsulatum var. capsulatum, (ii) class 2 North American H. capsulatum var. capsulatum, (iii) Central American H. capsulatum var. capsulatum, (iv) South American H. capsulatum var. capsulatum group A, (v) South American H. capsulatum var. capsulatum group B, and (vi) H. capsulatum var. duboisii. Although the clades were generally well supported, the relationships among them were not resolved and the nearest outgroups (Blastomyces and Paracoccidioides) were too distant to unequivocally root the H. capsulatum tree. H. capsulatum var. farciminosum was found within the South American H. capsulatum var. capsulatum group A clade. With the exception of the South American H. capsulatum var. capsulatum group A clade, genetic distances within clades were an order of magnitude lower than those between clades, and each clade was supported by a number of shared derived nucleotide substitutions, leading to the conclusion that each clade was genetically isolated from the others. Under a phylogenetic species concept based on possession of multiple shared derived characters, as well as concordance of four gene genealogies, H. capsulatum could be considered to harbor six species instead of three varieties. PMID- 9986829 TI - Validation of binary typing for Staphylococcus aureus strains. AB - Most of the DNA-based methods for genetic typing of Staphylococcus aureus strains generate complex banding patterns. Therefore, we have developed a binary typing procedure involving strain-differentiating DNA probes which were generated on the basis of randomly amplified polymorphic DNA (RAPD) analysis. We present and validate the usefulness of 15 DNA probes, according to generally accepted performance criteria for molecular typing systems. RAPD analysis with multiple primers was performed on 376 S. aureus strains of which 97% were methicillin resistant (MRSA). Among the 1,128 RAPD patterns generated, 66 were selected which identified 124 unique DNA fragments. From these amplicons, only 12% turned out to be useful for isolate-specific binary typing. The nature of the RAPD-generated DNA fragments was investigated by partial DNA sequence analysis. Several homologies with known S. aureus sequences and with genes from other species were discovered; however, 87% of the probe sequences are of previously unknown origin. The locations of most of the DNA probes on the chromosome of S. aureus NCTC 8325 were determined by hybridization. Seven fragments were randomly dispersed along the genome, five were clustered within the 2500- to 2600-kb position of the genome, and the remaining four did not recognize complementary sequences in S. aureus NCTC 8325. A total of 103 S. aureus strains (69% MRSA) were used for the validation of the binary typing technique. The 15 DNA probes provided stable epidemiological markers, both in vitro (type consistency after serial passages on culture media) and in vivo (comparison of sequential isolates recovered from cases of persistent colonization). The discriminatory power of binary typing (D = 0.998) exceeded that of pulsed-field gel electrophoresis (D = 0.966) and RAPD analysis (D = 0.949). Reproducibility, measured by analyzing multiple strains belonging to a multitude of different epidemiological clusters, was comparable to that of other genotyping techniques used. Contribution of the DNA probes to the discriminatory power of the system was analyzed by comparison of dendrograms. This study demonstrates that binary typing is a robust tool for the genetic typing of S. aureus isolates. PMID- 9986830 TI - Detection of the 70-kilodalton histoplasma capsulatum antigen in serum of histoplasmosis patients: correlation between antigenemia and therapy during follow-up. AB - Histoplasmosis is an important systemic fungal infection, particularly among immunocompromised individuals, who may develop a progressive disseminated form which is often fatal if it is untreated. In such patients, the detection of antibody responses for both diagnosis and follow-up may be of limited use, whereas the detection of Histoplasma capsulatum var. capsulatum antigens may provide a more practical approach. We have recently described an inhibition enzyme-linked immunosorbent assay (ELISA) for the detection in patients' sera of a 69- to 70-kDa H. capsulatum var. capsulatum-specific antigen which appears to be useful in diagnosis. To investigate its potential for the follow-up of histoplasmosis patients during treatment, antigen titers in the sera of 16 patients presenting with different clinical forms of histoplasmosis were monitored at regular intervals for up to 80 weeks. Sera from four of five patients with the acute form of the disease showed rapid falls in antigenemia, becoming antigen negative by week 14 (range, weeks 10 to 16). Sera from four patients with disseminated histoplasmosis showed falls in antigen levels; three of them became antigen negative by week 32; the fourth patient became negative by week 48. In contrast, antigen titers in four of six AIDS patients with the disseminated form of the disease remained positive throughout follow-up. Sera from only one patient who presented with the chronic form of the disease were analyzed, and this individual's serum became antigen negative by week 9. The inhibition ELISA is shown to be of particular use in the monitoring of non-AIDS patients with the acute and disseminated forms of the disease and may complement existing means of follow-up. PMID- 9986831 TI - Head-to-head evaluation of five chlamydia tests relative to a quality-assured culture standard. AB - Nucleic acid amplification tests offer superior sensitivity for the detection of Chlamydia trachomatis infection, but many laboratories still use nonamplification methods because of the lower cost and ease of use. In spite of their availability for more than a decade, few studies have directly compared the nonamplification tests. Such comparisons are still needed in addition to studies that directly compare individual nonamplification and amplification tests. The purpose of this study was to evaluate and compare the performance characteristics relative to culture of five different tests for the detection of C. trachomatis with and without confirmation of positive results. The tests were applied to endocervical specimens from 4,980 women attending family planning clinics in the northwestern United States. The five nonculture tests included Chlamydiazyme (Abbott), MicroTrak direct fluorescent antibody (DFA) (Syva), MicroTrak enzyme immunoassay (EIA) (Syva), Pace 2 (Gen-Probe), and Pathfinder EIA (Sanofi/Kallestad). All positive results obtained with a nonculture test (except MicroTrak DFA) were confirmed by testing the original specimens with a blocking antibody test (Chlamydiazyme), a cytospin DFA (MicroTrak EIA and Pathfinder EIA), and a probe competition assay (Pace 2). The prevalence of culture-proven chlamydia was 3.9%. The sensitivities of the nonculture tests were in a range from 62 to 75%, and significant differences between tests in terms of sensitivity were observed. The positive predictive value for each test was 0.85 or higher. The specificities of the nonculture tests without performance of confirmations were greater than 99%. Performing confirmatory tests eliminated nearly all of the false positives. PMID- 9986832 TI - PCR detection of adenovirus in a bone marrow transplant recipient: hemorrhagic cystitis as a presenting manifestation of disseminated disease. AB - Adenoviruses (AdV), causing fatal disseminated infections in bone marrow transplant (BMT) recipients, are associated not only with hemorrhagic cystitis (HC) but also with hepatitis, conjunctivitis, and viral interstitial pneumonia. The importance of this virus as a cause of disseminated disease, however, has remained underappreciated. AdV infection has been diagnosed primarily through the use of cell culture. The fact that cell culture is insensitive for detecting this virus has hindered recognition of the role that AdV may play in morbidity and mortality in BMT recipients. To emphasize these points, we describe a patient who presented with HC due to AdV serotype 11, genotype c, and died with disseminated infection. In addition to cell culture, this study used a newly developed PCR based method, capable of detecting all AdV serotypes tested, including different genotypes of serotype 11. The PCR result was positive in all culture-positive samples, including samples of urine, conjunctiva, and bronchoalveolar lavage (BAL). Importantly, the PCR method provided evidence of urinary shedding of AdV in a pretransplant, culture-negative specimen and showed dissemination in a subset of culture-negative specimens, including BAL, blood, and bone marrow samples. The lack of widespread awareness of the fact that localized infections may presage dissemination, and the previous associated lack of rapid, sensitive diagnostic assays, has impaired recognition of AdV infections in patients undergoing BMT. Early detection may contribute to therapy modification and avoidance of unwarranted diagnostic procedures. It may also assist in epidemiologic control of this highly infectious pathogen and lead to a renewed interest in preventive and therapeutic approaches. PMID- 9986833 TI - Rapid detection of epidemic strains of methicillin-resistant Staphylococcus aureus. AB - Fifty methicillin-resistant Staphylococcus aureus (MRSA) initial isolates obtained from patients hospitalized in the orthopedic clinic of the Frankfurt University Hospital and 150 methicillin-sensitive Staphylococcus aureus (MSSA) isolates were investigated in this study to determine whether the Slidex Staph Kit is capable of differentiating between MRSA and MSSA owing to its unique performance characteristics. The Slidex Staph-Kit is a combined latex hemagglutination test designed to detect clumping factor, protein A, and a specific surface immunogen for S. aureus. Clumping factor-positive strains cause erythrocytes sensitized with fibrinogen to hemagglutinate, thereby resulting in visible red clumps. S. aureus strains deficient in clumping factor agglutinate latex particles sensitized with specific antibodies against surface proteins of S. aureus, thereby resulting in visible white clumps. Our results demonstrate that white clumping has a 99% specificity as well as a 98% positive predictive value for MRSA. Clumping factor-negative MRSA, which have been reported to occur in several countries, are epidemic in the Frankfurt area and account for 80% of all MRSA initial isolates in the orthopedic clinic of the Frankfurt University Hospital. Genotyping of all MRSA isolates by macrorestriction analysis of chromosomal DNA revealed that 83% of clumping factor-negative MRSA are closely related to the "southern-German" epidemic strain. This is the first study demonstrating the Slidex Staph-Kit's capability for identifying epidemic clumping factor-negative S. aureus strains as methicillin resistant even prior to antimicrobial susceptibility testing. PMID- 9986834 TI - PCR detection of DNA specific for Trichosporon species in serum of patients with disseminated trichosporonosis. AB - Deep-seated trichosporonosis is a lethal opportunistic infection that disseminates rapidly and widely in immunocompromised patients, and early diagnosis is crucial for the treatment of this infection. We developed a novel nested-PCR assay that detects DNA specific for clinically important strains of Trichosporon in serum samples from patients with disseminated trichosporonosis. In this assay, two sets of oligonucleotide primers were derived from the sequence of 26S rRNA genes of Trichosporon asahii. The specific fragment was amplified from T. asahii and T. mucoides, but not from other microorganisms, including some other basidiomycetous fungi (Cryptococcus, Malassezia, Rhodotorula, and Sporobolomyces). Target DNA was detected by the nested PCR with as little as 5 fg of the extracted DNA of T. asahii. In a study using 11 clinical samples, the specific fragment was detected by the nested PCR in 64% (7 of 11) of sera from patients with histologically diagnosed disseminated trichosporonosis, while glucuronoxylomannan antigen was detected in only 54% (6 of 11) of the samples. Our new nested-PCR assay using serum samples can be performed repeatedly throughout the course of the disease. In addition, not only can it be used for early diagnosis of trichosporonosis, but it may also be beneficial for monitoring its progress or response to therapy. PMID- 9986835 TI - In vitro culture and drug sensitivity assay of Plasmodium falciparum with nonserum substitute and acute-phase sera. AB - The short-term in vitro growth of Plasmodium falciparum parasites in the asexual erythrocytic stage and the in vitro activities of eight standard antimalarial drugs were assessed and compared by using RPMI 1640 medium supplemented with 10% nonimmune human serum, 10% autologous or homologous acute-phase serum, or 0.5% Albumax I (lipid-enriched bovine serum albumin). In general, parasite growth was maximal with autologous (or homologous) serum, followed by Albumax I and nonimmune serum. The 50% inhibitory concentrations (IC50s) varied widely, depending on the serum or serum substitute. The comparison of IC50s between assays with autologous and nonimmune sera showed that monodesethylamodiaquine, halofantrine, pyrimethamine, and cycloguanil had similar IC50s. Although the IC50s of chloroquine, monodesethylamodiaquine, and dihydroartemisinin were similar with Albumax I and autologous sera, the IC50s of all test compounds obtained with Albumax I differed considerably from the corresponding values obtained with nonimmune serum. Our results suggest that Albumax I and autologous and homologous sera from symptomatic, malaria-infected patients may be useful alternative sources of serum for in vitro culture of P. falciparum isolates in the field. However, autologous sera and Albumax I do not seem to be suitable for the standardization of isotopic in vitro assays for all antimalarial drugs. PMID- 9986836 TI - Antimicrobial susceptibility patterns of Aeromonas jandaei, A. schubertii, A. trota, and A. veronii biotype veronii. AB - Fifty-six isolates of four Aeromonas species, which have been documented as causative agents of human infections or isolated from human clinical specimens, were subjected to antimicrobial susceptibility testing using a MicroScan WalkAway conventional (overnight incubation) gram-negative panel. The four species tested and the number of isolates of each were as follows: Aeromonas jandaei, 17; A. schubertii, 12; A. trota, 15; and A. veronii biotype veronii, 12. All isolates of A. trota were susceptible to all antimicrobial agents tested, except cefazolin (20% of isolates were resistant) and cefoxitin (13% of isolates were resistant). All isolates of A. schubertii and A. veronii biotype veronii, as well as 88% of A. jandaei isolates, were resistant to ampicillin. Resistance to ampicillin sulbactam ranged from 25% of A. schubertii strains to 100% of A. veronii biotype veronii strains. Cefazolin resistance ranged from 17% of A. veronii biotype veronii isolates to 59% of A. jandaei isolates. Imipenem resistance was detected in 65% of A. jandaei strains and 67% of A. veronii biotype veronii strains. A. jandaei displayed resistance to piperacillin and ticarcillin in 53 and 71% of the isolates, respectively. A. veronii biotype veronii strains were 100% susceptible to piperacillin and 100% resistant to ticarcillin. These antibiogram data may be useful in establishing the identification of these four species when members of the genus Aeromonas are isolated from human clinical sources. PMID- 9986837 TI - Usefulness of PCR and antigen latex agglutination test with samples obtained by transthoracic needle aspiration for diagnosis of pneumococcal pneumonia. AB - In a large number of cases, the etiology of community-acquired pneumonia (CAP) is not established. Some cases are probably caused by Streptococcus pneumoniae. Transthoracic needle aspiration (TNA) culture has a limited sensitivity which might be improved by antigen detection or gene amplification techniques. We evaluated the capacity of a PCR assay and a latex agglutination test to detect S. pneumoniae in samples obtained by TNA from 95 patients with moderate-to-severe CAP. Latex agglutination and PCR had sensitivities of 52.2 and 91.3%, specificities of 88.7 and 83.3%, positive predictive values of 62.3 and 65.6%, and negative predictive values of 83.3 and 96.5%, respectively, when culture techniques were used as the "gold standard." When we considered expanded criteria for the diagnosis of pneumococcal pneumonia as a standard for our calculations, latex agglutination and PCR had sensitivities of 53.6 and 89.7%, specificities of 93.0 and 90.0%, positive predictive values of 78.9 and 81.3%, and negative predictive values of 80.3 and 94.7%, respectively. The additional diagnosis provided by the PCR assay compared to latex agglutination was 12.2% (95% confidence interval of the difference from 0.4 to 20. 1%). PCR was more sensitive than TNA culture, particularly in patients who had received prior antibiotic therapy (83.3 versus 33. 3%). Although PCR is a very sensitive and specific technique, it has not proved to be cost-effective in clinical practice. Conversely, latex agglutination is a fast and simple method whose results might have significant implications for initial antibiotic therapy. PMID- 9986838 TI - Genetic multilocus studies of different strains of Cryptococcus neoformans: taxonomy and genetic structure. AB - The genotypes of 107 strains of Cryptococcus isolated from the environment or from patients from various geographical areas were determined by multilocus enzyme electrophoresis (MLEE). We analyzed the relationships between genotype structure and serotype and between genotype structure and strain origin. Twelve of the 14 enzyme-encoding loci studied were polymorphic, giving rise to 48 electrophoretic types. The genotypes of C. neoformans and C. laurentii were very similar. MLEE could not distinguish between these two pathogenic species. A correlation between the genetic multilocus structure and the origin of the sample (from the environment or patients) existed. A second analysis detected a correlation between genotype distribution and serotype. The second analysis considered three serotype groups (B, C, and A plus D plus A/D), proving that serotypes A, D, and A/D are closely related. MLEE is a useful epidemiological tool for improving our understanding of the biology of this fungus. PMID- 9986839 TI - Sensitivity and specificity of dipstick tests for rapid diagnosis of malaria in nonimmune travelers. AB - Swift diagnosis of Plasmodium falciparum malaria in areas where the disease is not endemic is frequently complicated by the lack of experience on the side of involved laboratory personal. Diagnostic tools based on the dipstick principle for the detection of plasmodial histidine-rich protein 2 (HRP-2) and parasite specific lactate dehydrogenase (pLDH), respectively, have become available for the qualitative detection of P. falciparum malaria. In order to evaluate two of the currently available assays, specimens from 231 patients were screened during a prospective multicenter study. Among the screened specimens, samples from 53 patients (22.9%) were positive for P. falciparum malaria by microscopy and/or PCR. While the test kit based on the detection of HRP-2 performed with a sensitivity of 92.5% and a specificity of 98.3%, the kit for the detection of pLDH showed a sensitivity of 88.5% and a specificity of 99.4%. Dipstick tests have the potential of enhancing speed and accuracy of the diagnosis of P. falciparum malaria, especially if nonspecialized laboratories are involved. PMID- 9986840 TI - Dual qualitative-quantitative nested PCR for detection of JC virus in cerebrospinal fluid: high potential for evaluation and monitoring of progressive multifocal leukoencephalopathy in AIDS patients receiving highly active antiretroviral therapy. AB - JC polyomavirus (JCV) is the causative agent of progressive multifocal leukoencephalopathy (PML), a central nervous system infection that mainly affects AIDS patients. The extensive application of highly active antiretroviral therapy (HAART) is leading to the appearance of "long-term" survival PML patients. A reliable and feasible qualitative-quantitative test for both the detection of JCV and follow-up of its viral burden in this emerging group of patients is clearly required. With this aim, a dual qualitative-quantitative nested PCR is presented in this study for the analysis of JCV DNA in cerebrospinal fluid (CSF). Two newly designed internal controls, one competitive and the other noncompetitive, have been constructed to adapt this PCR to either measure the JCV burden or to allow a highly confident determination of JCV presence or clearance. The analytical sensitivity of the technique allows the detection of 0.01 fg (three genomes) of JCV DNA. Its qualitative application has been evaluated by analyzing single CSF samples from a group of 17 patients with PML and a control group of 20 patients with diverse neurological conditions other than PML, yielding sensitivity and specificity values of 100 and 90%, respectively. The quantitative application has been evaluated in vitro in blind tests with samples including serial dilutions of JCV, and in all cases the samples were successfully ordered considering the JCV titer. The dual quantitative-qualitative application offered by this nested PCR may provide an answer to the new requirements for evaluating and finely monitoring PML in AIDS patients receiving HAART. PMID- 9986841 TI - Lactobacillus species identification, H2O2 production, and antibiotic resistance and correlation with human clinical status. AB - Lactobacilli recovered from the blood, cerebrospinal fluid, respiratory tract, and gut of 20 hospitalized immunocompromised septic patients were analyzed. Biochemical carbohydrate fermentation and total soluble cell protein profiles were used to identify the species. Hydrogen peroxide production was measured. Susceptibility to 19 antibiotics was tested by a diffusion method, and the MICs of benzylpenicillin, amoxicillin, imipenem, erythromycin, vancomycin, gentamicin, and levofloxacin were determined. A small number of species produced H2O2, and antibiotic susceptibilities were species related. Eighteen (90%) of the isolates were L. rhamnosus, one was L. paracasei subsp. paracasei, and one was L. crispatus. L. rhamnosus, L. paracasei subsp. paracasei isolates, and the type strains were neither H2O2 producers nor vancomycin susceptible (MICs, >/=256 microgram/ml). L. crispatus, as well as most of the type strains of lactobacilli which belong to the L. acidophilus group, was an H2O2 producer and vancomycin susceptible (MICs, <4 microgram/ml). PMID- 9986842 TI - Cholera in Vietnam: changes in genotypes and emergence of class I integrons containing aminoglycoside resistance gene cassettes in vibrio cholerae O1 strains isolated from 1979 to 1996. AB - The number of cholera cases and the mortality rates reported from different regions of Vietnam varied considerably in the period from 1979 to 1996, with between 2,500 and 6,000 cases reported annually from 1992 to 1995. Annual mortality rates ranged from 2.0 to 9.6% from 1979 to 1983 to less than 1.8% after 1983. Major cholera outbreaks were reported from the High Plateau region for the first time in 1994 and 1995; this is an area with limited access to health services and safe drinking-water supplies. All cases were associated with Vibrio cholerae O1. Using ribotyping, cholera toxin (CT) genotyping, and characterization of antibiotic susceptibility patterns and antibiotic resistance genes by PCR, we show that strains isolated after 1990 were clearly different from strains isolated before 1991. In contrast to strains isolated before 1991, 94% of 104 strains isolated after 1990 showed an identical ribotype R1, were resistant to sulfamethoxazole and streptomycin, and showed a different CT genotype. Furthermore, PCR analysis revealed that sulfamethoxazole-resistant strains harbored class I integrons containing a gene cassette ant(3")-1a encoding resistance to streptomycin and spectinomycin. This is, to our knowledge, the first report of class I integrons in V. cholerae. The development of cholera and the changes in the phenotypic and genotypic properties of V. cholerae O1 shown in the present study highlight the importance of monitoring V. cholerae O1 in Vietnam as in other parts of the world. In particular, the emergence of the new ribotype R1 strain containing class I integrons should be further studied. PMID- 9986843 TI - Evaluation of two commercial kits and arbitrarily primed PCR for identification and differentiation of Actinobacillus actinomycetemcomitans, Haemophilus aphrophilus, and Haemophilus paraphrophilus. AB - The closely related species Actinobacillus actinomycetemcomitans, Haemophilus aphrophilus, and Haemophilus paraphrophilus are common findings in oral microbiota. The aims of this study were to evaluate the applicability of the Rapid NH and API ZYM kits and arbitrarily primed PCR (AP-PCR) in the identification and differentiation of the three species from each other. The material included 62 clinical isolates and three reference strains of A. actinomycetemcomitans representing the 5 serotypes and 18 AP-PCR genotypes. Haemophilus species included 12 clinical isolates and 11 reference strains of H. aphrophilus, H. paraphrophilus, and 5 other species. For the PCR amplification, the oligonucleotide 5'-CAGCACCCAC-3' was used as a primer. Contrary to the consistent performance of API ZYM, the Rapid NH system was able to identify only 10 of 65 (15%) A. actinomycetemcomitans isolates, whereas all Haemophilus species were correctly identified. The API ZYM test differentiated A. actinomycetemcomitans from H. aphrophilus and H. paraphrophilus by negative beta galactosidase and alpha-glucosidase reactions and a positive esterase lipase reaction. However, the API ZYM test was unable to differentiate H. aphrophilus from H. paraphrophilus, it also could not differentiate A. actinomycetemcomitans serotypes from each other. Among the H. aphrophilus isolates three AP-PCR genotypes and among H. paraphrophilus isolates only one AP-PCR genotype, distinct from those of A. actinomycetemcomitans, were found. The Rapid NH test showed poor ability to identify clinical isolates of all A. actinomycetemcomitans serotypes. Moreover, AP-PCR genotyping proved to be a rapid method for the species differentiation of A. actinomycetemcomitans, H. aphrophilus, and H. paraphrophilus. PMID- 9986844 TI - Multicenter evaluation of the BACTEC MGIT 960 system for recovery of mycobacteria. AB - We evaluated the BACTEC MGIT 960 system, which is a fully automated, noninvasive system for the growth and detection of mycobacteria with a capacity to incubate and continuously monitor 960 7-ml culture tubes. We studied 3,330 specimens, 2,210 respiratory and 1,120 nonrespiratory specimens, collected from 2,346 patients treated at six sites. Processed specimens were inoculated into the BACTEC MGIT 960 and BACTEC 460 TB systems, as well as onto Lowenstein-Jensen slants and Middlebrook 7H11/7H11 selective plates. From all culture systems, a total of 362 isolates of mycobacteria were recovered; these were recovered from 353 specimens collected from 247 patients. The greatest number of isolates of mycobacteria (289, or 80% of the 362 isolates) was recovered with the BACTEC MGIT 960, followed by the BACTEC 460 TB (271, or 75%) and solid media (250, or 69%). From all culture systems a total of 132 isolates of Mycobacterium tuberculosis complex were recovered. The greatest number of isolates of M. tuberculosis complex was recovered when liquid medium was combined with conventional solid media; the number recovered with BACTEC 460 TB plus solid media was 128 (97%), that recovered with BACTEC MGIT 960 plus solid media was 121 (92%), that recovered with BACTEC 460 TB was 119 (90%) and that recovered with all solid media combined was 105 (79%). The recovery with BACTEC MGIT 960 alone was 102 (77%). The mean times to detection (TTD) for M. tuberculosis complex were 14.4 days for BACTEC MGIT, 15.2 days for BACTEC 460 TB, and 24.1 days for solid media. The numbers of isolates of Mycobacterium avium complex (MAC) recovered were 172 (100%) for all systems, 147 (85%) for BACTEC MGIT 960, 123 (72%) for BACTEC 460 TB, and 106 (62%) for all solid media combined. The TTD for MAC in each system were 10.0 days for BACTEC MGIT 960, 10.4 days for BACTEC 460 TB, and 25.9 days for solid media. Breakthrough contamination rates (percentages of isolates) for each of the systems were 8.1% for BACTEC MGIT 960, 4.9% for BACTEC 460 TB, and 21.1% for all solid media combined. PMID- 9986845 TI - Impact of microbiology practice on cumulative prevalence of respiratory tract bacteria in patients with cystic fibrosis. AB - Investigators participating in the Epidemiologic Study of Cystic Fibrosis project began to collect microbiological, pulmonary, and nutritional data on cystic fibrosis (CF) patients at 180 North American sites in 1994. Part of this study was a survey undertaken in August 1995 to determine microbiology laboratory practices with regard to pulmonary specimens from CF patients. The survey included a section on test ordering, completed by a site clinician, and a section on test performance and reporting, completed by each site's clinical microbiology laboratory staff. Seventy-nine percent of the surveys were returned. There was intersite consistency of microbiology laboratory practices in most cases. The majority of sites follow most of the CF Foundation consensus conference recommendations. There were differences in the frequency at which specimens for culture were obtained, in the use of selective media for Staphylococcus aureus and Haemophilus influenzae, and in the use of a prolonged incubation for Burkholderia cepacia. These variations in practice contribute to prevalence differences among sites and may result in differences in clinical care. PMID- 9986846 TI - Spread of amikacin resistance in Acinetobacter baumannii strains isolated in Spain due to an epidemic strain. AB - Sixteen amikacin-resistant clinical Acinetobacter baumannii isolates from nine different hospitals in Spain were investigated to determine whether the high incidence of amikacin-resistant A. baumannii was due to the dissemination of an amikacin-resistant strain or to the spread of an amikacin resistance gene. The epidemiological relationship studied by repetitive extragenic palindromic PCR and low-frequency restriction analysis of chromosomal DNA showed that the same clone was isolated in eight of nine hospitals, although other clones were also found. The strains were studied for the presence of the aph(3')-VIa and aac(6')-I genes, which encode enzymes which inactivate amikacin, by PCR. All 16 clinical isolates had positive PCRs with primers specific for the amplification of the aph(3')-VIa gene, whereas none had a positive reaction for the amplification of the aac(6')-I gene. Therefore, the high incidence of amikacin resistance among clinical A. baumannii isolates in Spain was mainly due to an epidemic strain, although the spread of the aph(3')-VI gene cannot be ruled out. PMID- 9986847 TI - Comparison of CHROMagar Salmonella medium and hektoen enteric agar for isolation of salmonellae from stool samples. AB - CHROMagar Salmonella (CAS), a new chromogenic medium, was retrospectively compared to Hektoen enteric agar (HEA) with 501 Salmonella stock isolates and was then prospectively compared to HEA for the detection and presumptive identification of Salmonella spp. with 508 stool samples before and after enrichment. All stock cultures (100%), including cultures of H2S-negative isolates, yielded typical mauve colonies on CAS, while 497 (99%) isolates produced typical lactose-negative, black-centered colonies on HEA. Following overnight incubation at 37 degreesC, a total of 20 Salmonella strains were isolated from the 508 clinical samples. Sensitivities for primary plating and after enrichment were 95% (19 isolates) and 100% (20 isolates), respectively, for CAS and 80% (16 isolates) and 100% (20 isolates), respectively, for HEA. The specificity of CAS (88.9%) was significantly higher than that of HEA (78.5%; P < 0.0001). On the basis of its good sensitivity and specificity, CAS medium can be recommended for use for primary plating when human stool samples are screened for Salmonella spp. PMID- 9986848 TI - ABC medium, a new chromogenic agar for selective isolation of Salmonella spp. AB - We describe a new chromogenic agar medium, ABC medium (alphabeta-chromogenic medium), which includes two substrates, 3, 4-cyclohexenoesculetin-beta-D galactoside and 5-bromo-4-chloro-3-indolyl-alpha-D-galactopyranoside, to facilitate the selective isolation of Salmonella spp. This medium exploits the fact that Salmonella spp. may be distinguished from other members of the family Enterobacteriaceae by the presence of alpha-galactosidase activity in the absence of beta-galactosidase activity. A total of 1, 022 strains of Salmonella spp. and 300 other gram-negative strains were inoculated onto this medium. Of these, 1,019 (99.7%) strains of Salmonella spp. produced a characteristic green colony, whereas only 1 strain (0.33%) of non-Salmonella produced a green colony. A total of 283 stool samples were cultured onto desoxycholate citrate (DC) agar and ABC medium by direct inoculation and after selective enrichment in selenite broth. Overall, the sensitivity and specificity were superior for ABC medium (100 and 90.5%, respectively) than for DC agar (88 and 26.9%, respectively). We conclude that ABC medium offers a high degree of specificity for the detection of Salmonella spp. in stool samples. PMID- 9986849 TI - Isolation of Abiotrophia adiacens from a brain abscess which developed in a patient after neurosurgery. AB - We report the case of a patient who developed a large brain abscess after neurosurgery. Cerebrospinal fluid from the abscess drainage yielded Abiotrophia adiacens-specific PCR products and microorganisms that were identified by conventional microbiological methods and by 16S ribosomal DNA analysis as Abiotrophia adiacens, which was formerly classified as a member of nutritionally variant streptococci. PMID- 9986850 TI - Comparison of five PCR methods for detection of Helicobacter pylori DNA in gastric tissues. AB - Five different PCR methods for the detection of Helicobacter pylori were evaluated. The results of this study indicate that of the five PCR methods examined, the ureC (glmM) gene PCR is the most sensitive and specific for the detection of H. pylori in gastric biopsy specimens. PMID- 9986851 TI - Case report and molecular analysis of subacute sclerosing panencephalitis in a South African Child. AB - This is the first case of subacute sclerosing panencephalitis from South Africa in which the molecular characteristics of the causative measles virus were examined. The virus found is classified as genotype D3, which has not previously been found in Africa and was last circulating in the United States before 1992. PMID- 9986852 TI - Clonal diversity of Chilean isolates of enterohemorrhagic Escherichia coli from patients with hemolytic-uremic syndrome, asymptomatic subjects, animal reservoirs, and food products. AB - To determine clonal relationship among Chilean enterohemorrhagic Escherichia coli (EHEC) strains from different sources (clinical infections, animal reservoirs, and food), 54 EHEC isolates (44 of E. coli O157, 5 of E. coli O111, and 5 of E. coli O26) were characterized for virulence genes by colony blot hybridization and by pulsed-field gel electrophoresis (PFGE). By colony blotting, 12 different genotypes were identified among the 44 E. coli O157 isolates analyzed, of which the genetic profile stx1+ stx2+ hly+ eae+ was the most prevalent. All human O157 strains that were associated with sporadic cases of hemolytic-uremic syndrome (HUS) carried both the stx1 and stx2 toxin-encoding genes and were eaeA positive. Only 9 of 13 isolates from human controls were stx1+ stx2+, and 8 carried the eaeA gene. Comparison of profiles obtained by PFGE of XbaI-digested genomic DNA showed a great diversity among the E. coli O157 isolates, with 37 different profiles among 39 isolates analyzed. Cluster analysis of PFGE profiles showed a wide distribution of clinical isolates obtained from HUS cases and asymptomatic individuals and a clonal relationship among O157 isolates obtained from HUS cases and pigs. Analysis of virulence genes showed that a correlation exists among strains with the genotype stx1+ stx2+ eae+ and pathogenic potential. A larger difference in the PFGE restriction patterns was observed among the EHEC strains of serogroups O26 and O111. These results indicate that several different EHEC clones circulate in Chile and suggest that pigs are an important animal reservoir for human infections by EHEC. Guidelines have been proposed for better practices in the slaughter of animals in Chile. PMID- 9986853 TI - Assessment of use of the COBAS AMPLICOR system with BACTEC 12B cultures for rapid detection of frequently identified mycobacteria. AB - The use of the COBAS AMPLICOR System (Roche Molecular Diagnostics, Basel, Switzerland), the only automated system for PCR testing, was evaluated for a rapid identification of mycobacteria with positive BACTEC 12B cultures. Two hundred ninety-six specimens with a growth index of >/=30 were analyzed for the presence of Mycobacterium tuberculosis complex, Mycobacterium avium, and Mycobacterium intracellulare. Compared to traditional methods and provided that samples with PCR inhibition are retested at a 1:10 dilution, the sensitivity and specificity of the COBAS AMPLICOR System with BACTEC 12B cultures were 100 and 98%, respectively. The COBAS AMPLICOR method is rapid and reliable for identifying the most common mycobacteria in cultures. PMID- 9986854 TI - Isolation of Legionella pneumophila by centrifugation of shell vial cell cultures from multiple liver and lung abscesses. AB - A 7-year-old girl was admitted to the hospital with acute lymphoblastic leukemia and was treated with allogenic cord blood transplantation. At day 30 after graft, she developed a fever and multiple nodular lesions disseminated in the liver and lungs. All bacterial cultures attempted on liver and lung biopsy specimens and blood remained sterile on standard axenic media. However, inoculation of liver and lung biopsy specimens on eukaryotic cell monolayers by the centrifugation shell vial technique (M. Marrero and D. Raoult, Am. J. Trop. Med. Hyg. 40:197 199, 1989) led to the recovery of a strain of Legionella pneumophila serogroup 1, identified by 16S rRNA gene amplification and sequencing and serotyping. Our findings demonstrate that the centrifugation-cell culture method, which has previously been useful for the isolation of other strictly or facultatively intracellular bacteria, can also serve as a method for the recovery of L. pneumophila from clinical material. PMID- 9986855 TI - The IS6110 restriction fragment length polymorphism in particular multidrug resistant Mycobacterium tuberculosis strains may evolve too fast for reliable use in outbreak investigation. AB - To study possible nosocomial transmission of multidrug-resistant (MDR) Mycobacterium tuberculosis, strain types and other information on 24, mostly human immunodeficiency virus-positive patients, were collected. Isolates from 11 patients had identical IS6110 restriction fragment length polymorphism (RFLP) patterns as well as spoligotype patterns and resistance profiles. Noticeably, nine other isolates from related cases also exhibited identical spoligotypes but slightly different RFLP patterns. These results indicate that for some MDR strains, the evolutionary clock of IS6110 RFLP may run too fast for reliable interpretation of strain typing results over a period of a few years. PMID- 9986856 TI - Evaluation of the ultrasensitive Roche Amplicor HIV-1 monitor assay for quantitation of human immunodeficiency virus type 1 RNA. AB - The ultrasensitive Amplicor HIV-1 Monitor test (Roche Diagnostic Systems) was evaluated for precision, linearity, and sensitivity and was compared to the standard Amplicor assay. The ultrasensitive assay reliably quantified samples in the range from 50 to 50,000 human immunodeficiency virus type 1 RNA copies/ml with acceptable correlation with the standard Amplicor test. PMID- 9986857 TI - Comparative evaluation of first- and second-generation digene hybrid capture assays for detection of human papillomaviruses associated with high or intermediate risk for cervical cancer. AB - In the present study we comparatively evaluated the first- and second-generation Digene Hybrid Capture assays for detection of human papillomaviruses (HPV) associated with high or intermediate risk for cervical cancer in cervical specimens. Concordant results were obtained with 468 of 483 (96.8%) specimens. All 15 specimens which gave repeatedly discordant results were positive by the second-generation test only, and 14 of them tested PCR positive. The enhanced sensitivity of the second-generation assay is mainly a result of the reformulation of hybridization reagents and, to a lesser extent, a result of the addition of new HPV probes. PMID- 9986858 TI - Antimicrobial resistance and serotype distribution of Streptococcus pneumoniae strains causing childhood infections in Bangladesh, 1993 to 1997. AB - Three hundred sixty-two Streptococcus pneumoniae strains were isolated from children under 5 years of age at Dhaka Shishu (Children) Hospital from 1993 to 1997. The strains were isolated from blood (n = 105), CSF (n = 164), ear swab (n = 61), eye swab (n = 20), and pus (n = 12). Of the 362 isolates, 42 (11.6%) showed intermediate resistance (MIC, <0.1 microgram/ml) and only 4 (1.1%) showed complete resistance (MIC, >2.0 microgram/ml) to penicillin. Penicillin resistance exhibited a strong relationship with serotype 14; 47.8% of the penicillin resistant strains belonged to this type. A remarkably high (64.1%) resistance to co-trimoxazole was observed, along with a significant increase during the time period studied; there was no relationship to capsular type. By way of contrast, penicillin resistance did not show any significant change during the study period. Resistance to chloramphenicol (2.2%) and erythromycin (1.1%) was rare. The high resistance to co-trimoxazole and its increasing trend demand elucidation of the clinical impact of pneumonia treatment by this antimicrobial and reconsideration of the World Health Organization recommendation for co trimoxazole administration to children with community-acquired pneumonia at the health care worker level in Bangladesh. PMID- 9986859 TI - Prevalence of enterotoxigenic Bacteroides fragilis in children with diarrhea in Japan. AB - In age-matched controlled studies performed in Japan, enterotoxigenic Bacteroides fragilis was isolated from 14.9% of 114 children aged 1 to 14 years with antibiotic-unassociated diarrhea (AUD) and 6.5% of 108 children aged 1 to 6 years with antibiotic-associated diarrhea (AAD). The difference in comparison with control children, was significant for AUD children but not AAD children. PMID- 9986860 TI - Application of dried blood spot specimens for serologic subtyping of human immunodeficiency virus type 1 in Thailand. AB - Dried blood spot (DBS) specimens were assessed as an alternative to plasma for human immunodeficiency virus type 1 (HIV-1) serotyping by V3 loop peptide enzyme immunoassay. Nested PCR capable of distinguishing HIV-1 subtypes B and E was used as the reference standard. Ninety-two percent of DBS samples were typeable as either HIV-1 subtype B or E. Serotype results with DBS and plasma were identical for 254 of 257 specimens. A simple DBS collection method provides a convenient alternative for conducting HIV-1 serotype surveillance while retaining sensitivity and specificity. PMID- 9986861 TI - Human phaeohyphomycotic osteomyelitis caused by the coelomycete Phomopsis saccardo 1905: criteria for identification, case history, and therapy. AB - The Sphaeropsidales, coelomycetous fungi producing asexual conidia within enclosed conidiomata (pycnidia), are saprobic on numerous vascular plants. Despite their ubiquitous nature, only a limited number of genera have been documented as causing human disease. We report what we believe to be the first human case of osteomyelitis due to a Phomopsis species in a chronically immunosuppressed female. The patient developed a subcutaneous abscess on the distal phalanx of the right fourth finger complicated by osteomyelitis. Operative specimens revealed fungal hyphae and a pure culture of mould. The patient was treated with a 6-month course of itraconazole. At 16 months of follow-up, she remained free of recurrence. Phomopsis species differ from the similar, more frequently reported Phoma species by having immersed, thick-walled, multiloculate conidiomata and by the production of alpha (short, ellipsoidal) and beta (long, filamentous) conidia. PMID- 9986862 TI - Reproducibility and performance of the second-generation branched-DNA assay in routine quantification of human immunodeficiency virus type 1 RNA in plasma. AB - We examined the reproducibility of a second-generation branched-DNA (bDNA) assay (Quantiplex HIV RNA 2.0) for quantification of human immunodeficiency virus type 1 (HIV-1) RNA in plasma by retesting 325 specimens on separate runs and on different lots. The performance of the bDNA test was also assessed by data analysis obtained during routine testing of 15,365 specimens. Upon retesting, 96 and 86% of specimens displaying RNA levels above 5,000 and between 500 and 5, 000 copies/ml, respectively, showed less than a 0.3 log10 (twofold) difference with their initial values. Assay variability was found to increase as viral load decreased. Overall, the bDNA version 2.0 assay was found to be a reproducible and efficient test for routine quantification of HIV-1 RNA in plasma. PMID- 9986863 TI - Comparison of simple and rapid methods for identifying enterococci intrinsically resistant to vancomycin. AB - Three different methodologies, reduction of litmus milk (LM) and acidification of arabinose (ARA), acidification of methyl-alpha-D-glucopyranoside (MGP), and rapid motility (RM), for differentiating isolates of Enterococcus casseliflavus and Enterococcus gallinarum (intrinsically vancomycin-resistant enterococci [IVRE]) from Enterococcus faecalis and Enterococcus faecium were evaluated. All 33 isolates of E. faecalis tested reduced LM within 4 h and were negative in all other tests, while the 53 isolates of E. faecium were ARA positive only. In contrast, 45 of 46 (98%) IVRE isolates examined (26 E. casseliflavus and 20 E. gallinarum isolates) acidified MGP, 41 of 46 (89%) were LM and ARA positive, and 45 of 46 (98%) were RM positive. Acidification of MGP was therefore the single most useful test for differentiating IVRE from vancomycin-resistant E. faecium and E. faecalis; however, a combination of LM-ARA and RM testing enabled the correct designation of organisms without the need for overnight incubation. PMID- 9986864 TI - Variation in structure and location of VanA glycopeptide resistance elements among enterococci from a single patient. AB - Forty-six VanA glycopeptide-resistant enterococci (GRE) from a single patient were investigated for variation in structure and location of VanA resistance elements. Together with identification to species level and pulsed-field gel electrophoresis, these data divided the GRE into 10 groups and subgroups. Combining data in this manner appears helpful when investigating the epidemiology of GRE. PMID- 9986865 TI - Comparison of the API Candida system with the AUXACOLOR system for identification of common yeast pathogens. AB - Two commercial systems for the identification of yeasts were evaluated by using 159 clinical isolates that had also been identified by conventional biochemical and morphological methods. The API Candida system correctly identified 146 isolates (91.8%), and the AUXACOLOR system correctly identified 145 isolates (91.2%). However, of the 146 isolates identified by the API Candida system, 23 required supplemental biochemical tests or morphological assessment to obtain the correct identification. The AUXACOLOR system gave no identification in 13 cases (8.2%), while the API Candida system gave an unreadable profile in only one case. Incorrect identifications were more common with the API Candida system (12 isolates; 7.5%) than with the AUXACOLOR system (1 isolate; 0.6%). PMID- 9986866 TI - Chronic urinary tract infection due to Candida utilis. AB - An elderly male was seen at an outpatient urology clinic over a period of 3 years with repeat urine specimens containing 10(4) to 10(5) CFU of a "Candida species, not C. albicans." The urine specimens were described as infected due to the presence of pyuria, but no antifungal therapy was administered. On two occasions, the patient presented to the emergency room and urine specimens were sent to the clinical microbiology laboratory. On both occasions, a yeast was isolated at concentrations of >10(5) CFU/ml. The organism was identified as the anamorphic yeast Candida utilis (teleomorph: Pichia jadinii) by conventional methods. Molecular methods, including karyotyping and restriction enzyme analysis, confirmed that the isolates were identical and were C. utilis. The patient developed benign prostatic hypertrophy and chronic obstructive pulmonary disease during the 3-year course. This report is the first demonstration of the isolation of the industrially important yeast C. utilis from a urinary tract infection. In the present case, the organism was associated with chronic, symptomatic disease. The significance of this unusual, low-virulence isolate from a case of urinary tract infection is discussed. PMID- 9986867 TI - Unexpected cross-reaction with Fusobacterium necrophorum in a PCR for detection of mycoplasmas. AB - Cross-reactions with Fusobacterium necrophorum were found in a PCR designed for detection of a wide range of mycoplasma species. Twenty-five strains of Fusobacterium were examined; all 14 F. necrophorum strains reacted positively, whereas all 7 Fusobacterium nucleatum strains reacted negatively. Two strains that were not F. necrophorum yielded variable results. PMID- 9986868 TI - Identification of contaminating fungal DNA sequences in Zymolyase. AB - When different preparations of Zymolyase were included in the pretreatment protocol of a panfungal PCR assay using a primer system for the 18S rRNA gene, an amplification product occurred in negative controls. The amplified fragment showed 100.0% sequence identity to the Saccharomyces sensu stricto complex and Kluyveromyces lodderae. Lyticase, lysing enzymes, and proteinase K appeared to be free from fungal DNA. PMID- 9986869 TI - Optimal detection and identification of Mycobacterium haemophilum in specimens from pediatric patients with cervical lymphadenopathy. AB - Acid-fast bacilli from pediatric patients with lymphadenopathy were detected in the BACTEC radiometric system and in MB Redox broth, but not on Lowenstein Jensen medium. PCR amplification identified the isolates as Mycobacterium haemophilum, which has special nutrition requirements (iron supplements) for growth. Suitable culture medium ensures optimal recovery of this microorganism, avoiding underdiagnosis. PMID- 9986870 TI - Justification for use of a single trichrome stain as the sole means for routine detection of intestinal parasites in concentrated stool specimens. AB - Of 12,321 stool samples analyzed over a 6-year interval, 870 (7.1%) were positive for a total of 1,019 parasites, of which 1,011 (99.2%) were found in trichrome stained smears of unconcentrated specimens while only 479 (47.0%) were detected in iodine-stained smears of concentrated samples. Stool specimens were next analyzed by trichrome staining of both unconcentrated and concentrated specimens preserved in either mercury-polyvinyl alcohol (PVA) or cupric PVA. Of 2,198 specimens, 171 (7.8%) were positive for a total of 208 parasites, 192 (92.3%) and 204 (98.1%) of which were found in the unconcentrated and concentrated specimens, respectively (P < 0.05). In our patient population, examination of a single trichrome-stained smear of a concentrated stool specimen is a cost-effective alternative to routinely analyzing both concentrated and unconcentrated specimens for parasites. PMID- 9986871 TI - Cryptococcus neoformans var. grubii: separate varietal status for Cryptococcus neoformans serotype A isolates. AB - Cryptococcus neoformans var. neoformans presently includes isolates which have been determined by the immunologic reactivity of their capsular polysaccharides to be serotype A and those which have been determined to be serotype D. However, recent analyses of the URA5 sequences and DNA fingerprinting patterns suggest significant genetic differences between the two serotypes. Therefore, we propose to recognize these genotypic distinctions, as well as previously reported phenotypic differences, by restricting C. neoformans var. neoformans to isolates which are serotype D and describing a new variety, C. neoformans var. grubii, for serotype A isolates. PMID- 9986872 TI - Aerobic and anaerobic microbiology of surgical-site infection following spinal fusion. AB - The aerobic and anaerobic microbiology of surgical-site infections (SSI) following spinal fusion was retrospectively studied. This was done by reviewing the clinical and microbiological records at the Naval Hospital in Bethesda, Md., from 1980 to 1992. Aspirates of pus from 25 infection sites showed bacterial growth. Aerobic bacteria only were recovered from 9 (36%) specimens, anaerobic bacteria only were recovered from 4 (16%), and mixed aerobic and anaerobic bacteria were recovered from 12 (48%). Sixty isolates were recovered: 38 aerobes (1.5 isolates per specimen) and 22 anaerobes (0.9 isolate per specimen). The predominant aerobes were Escherichia coli (n = 8) and Proteus sp. (n = 7). The predominant anaerobes were Bacteroides fragilis group (n = 9) and Peptostreptococcus sp. (n = 6) isolates. An increase in recovery of E. coli and B. fragilis was noted in patients with bowel or bladder incontinence. This study highlights the polymicrobial nature of SSI and the importance of anaerobic bacteria in SSI following spinal fusion. PMID- 9986873 TI - Use of restriction fragment analysis and sequencing of a serotype-specific region to type adenovirus isolates. AB - Restriction fragment analysis and sequencing of a serotype-specific region were used to type 12 and 2 clinical isolates, respectively. Both molecular methods produced clear-cut results that completely correlated with that of the neutralization test. PMID- 9986874 TI - Quality control in nucleic acid amplification methods: use of elementary probability theory. AB - Since it is not possible to state with certainty that contamination has occurred during a nucleic acid amplification assay in the absence of a positive result for a negative control, methods of elementary probability theory are used to illustrate how to identify those runs in which the possibility of contamination should be considered. The use of binomial and Poisson distributions and an analysis of clusters are presented with illustrative examples to demonstrate their use. PMID- 9986875 TI - hsp65 sequencing for identification of rapidly growing mycobacteria. AB - Partial sequencing of the hsp65 gene was used for the identification of rapidly growing mycobacteria (RGM). A 441-bp fragment (A. Telenti, F. Marchesi, M. Balz, F. Bally, E. Bottger, and T. Bodmer, J. Clin. Microbiol. 31:175-178, 1993) was amplified and sequenced by an automated fluorescence-based method involving capillary electrophoresis. Type strains of 10 RGM species were first studied. Each species had a unique nucleotide sequence, distinguishing it clearly from the other species. A panel of strains from the four main RGM species responsible for human infections, Mycobacterium abscessus, Mycobacterium chelonae, Mycobacterium fortuitum, and Mycobacterium peregrinum, was also studied. There were few sequence differences within each of these species (<2% of bases were different from the type strain sequence), and they had no effect on species assignment. hsp65 sequencing unambiguously differentiated M. chelonae and M. abscessus, two species difficult to identify by classical methods and 16S rRNA gene sequencing. The devised procedure is a rapid and reliable tool for the identification of RGM species. PMID- 9986876 TI - Comparative study of susceptibilities of germinated and ungerminated conidia of Aspergillus fumigatus to various antifungal agents. AB - Conidia are used as inocula for the in vitro susceptibility testing of Aspergillus fumigatus. Since the MIC is defined on the basis of visible mycelial growth, conidia should germinate and produce sporelings (germinated conidia) for monitoring of the growth inhibition and fungicidal activity of a drug. If a compound is capable of inhibiting germination of conidia while affecting or not affecting the growth of the organism, the MIC obtained will be the concentration of the drug required for the inhibition of conidial germination but not necessarily that required for inhibition of the growth of the organism. We investigated the susceptibility of germinated and ungerminated conidia to amphotericin B, itraconazole, voriconazole, and SCH56592. The MICs of various antifungal agents for germinated conidia were almost identical to those obtained for ungerminated conidia. In addition, both the germinated and ungerminated conidia were killed with almost equal efficiency by all of the compounds tested when exposed to the drugs for 24 h. These results suggest that either germinated or ungerminated conidia could be used as inocula for in vitro susceptibility studies of A. fumigatus with identical results. PMID- 9986877 TI - Streptococcus bovis clone causing two episodes of endocarditis 8 years apart. AB - A patient had endocarditis caused by Streptococcus bovis twice 8 years apart. According to pulsed-field gel electrophoresis (PFGE) the two isolates were identical. Seven unrelated blood isolates of S. bovis yielded unique PFGE patterns. Considering this heterogeneous population structure our findings demonstrate the long-term persistence of an S. bovis clone in a patient with recurrent endocarditis. PMID- 9986878 TI - Evaluation of the fungitest kit by using strains from human immunodeficiency virus-infected patients: study of azole drug susceptibility. AB - One hundred eighteen Candida clinical isolates from human immunodeficiency virus infected patients were tested for their susceptibilities to fluconazole and itraconazole by Fungitest and the National Committee for Clinical Laboratory Standards MIC method. Fungitest results depended on both yeast species and antifungal agents. This test is able to detect sensitive strains (97% agreement with results of the MIC method in tests with fluconazole and 84% agreement in tests with itraconazole) but has a poor capacity to detect resistant strains (26% agreement in tests with fluconazole and 5% agreement in tests with itraconazole). PMID- 9986879 TI - Identification of seven Treponema species in health- and disease-associated dental plaque by nested PCR. AB - Species-specific nested PCR was used to detect Treponema amylovorum, Treponema denticola, Treponema maltophilum, Treponema medium, Treponema pectinovorum, Treponema socranskii, and Treponema vincentii in dental plaque. Subjects with periodontitis harbored all species, but T. pectinovorum and T. vincentii were not found in plaque from disease-free subjects. PMID- 9986880 TI - In vitro susceptibilities of Candida dubliniensis isolates tested against the new triazole and echinocandin antifungal agents. AB - Candida dubliniensis is a newly recognized fungal pathogen causing mucosal disease in AIDS patients. Although preliminary studies indicate that most strains of C. dubliniensis are susceptible to established antifungal agents, fluconazole resistant strains have been detected. Furthermore, fluconazole-resistant strains are easily derived in vitro, and these strains exhibit increased expression of multidrug resistance transporters, especially MDR1. Because of the potential for the development of resistant strains of C. dubliniensis, it is prudent to explore the in vitro activities of several of the newer triazole and echinocandin antifungals against isolates of C. dubliniensis. In this study we tested 71 isolates of C. dubliniensis against the triazoles BMS-207147, Sch 56592, and voriconazole and a representative of the echinocandin class of antifungal agents, MK-0991. We compared the activities of these agents with those of the established antifungal agents fluconazole, itraconazole, amphotericin B, and 5-fluorocytosine (5FC) by using National Committee for Clinical Laboratory Standards microdilution reference methods. Our findings indicate that the vast majority of clinical isolates of C. dubliniensis are highly susceptible to both new and established antifungal agents. Strains with decreased susceptibilities to fluconazole remained susceptible to the investigational agents as well as to amphotericin B and 5FC. The increased potencies of the new triazole and echinocandin antifungal agents may provide effective therapeutic options for the treatment of infections due to C. dubliniensis. PMID- 9986882 TI - Pediatric cardiology: genetics PMID- 9986881 TI - Identification of Shigella flexneri subserotype 1c in rural Egypt. AB - In a population-based study of diarrhea in rural, northern Egypt, 60 Shigella flexneri strains were identified, of which 10 could not be definitively serotyped. Serological analysis with commercial reagents suggested that they were serotype 1, but the strains failed to react with subserotype 1a- or 1b-specific antibodies. All 10 strains reacted with MASF 1c, a monoclonal antibody specific for a provisional S. flexneri subserotype, 1c, first identified in Bangladesh and not previously detected outside of that region. Our results show that S. flexneri subserotype 1c is not unique to Bangladesh and that the inability to detect it may reflect both the limited use of suitable screening methods and the rarity of this subserotype. PMID- 9986883 TI - An introduction to molecular biology: gene structure, expression, and mutation. AB - This mini-review outlines DNA structure and the regulation of gene expression. It then discusses the nature of mutations, techniques employed to detect them, and the limitations of these techniques. PMID- 9986884 TI - Aortic arch anomalies associated with chromosome 22q11 deletion (CATCH 22). AB - Chromosome 22q11 deletion or CATCH 22 is associated with DiGeorge syndrome, conotruncal anomaly face syndrome, and velocardiofacial syndrome. Associated congenital heart diseases include tetralogy of Fallot, truncus arteriosus, and ventricular septal defect. Associated anomalies of the aortic arch, aortic branches, ductus arteriosus, and pulmonary arteries are more frequent in patients with the deletion than in those without the deletion. Associated anomalies include right aortic arch, cervical aorta, aberrant origin or isolation of the subclavian artery, the absence of the ductus arteriosus, major aortopulmonary collateral arteries, isolation of the left pulmonary artery, and vascular ring formed by the right aortic arch, retroesophageal aortic arch, and left descending aorta. PMID- 9986885 TI - Elastin mutation and cardiac disease. AB - Characterization of the molecular basis of structural cardiac disease includes elucidating the pathogenesis of certain vascular disease by demonstrating mutations of the Elastin gene as the cause of familial supravalvular aortic stenosis (SVAS) and Williams' syndrome (WS). Defining the etiology of SVAS has clinical implications in terms of prenatal and presymptomatic diagnosis and possible earlier intervention with medical therapy. This review considers the evidence relating Elastin mutations to SVAS and WS and outlines the possible mechanisms by which these mutations give rise to cardiac disease. Finally, the implications which Elastin mutation identification has on current clinical practice and future research directions are considered. PMID- 9986886 TI - Turner's syndrome: cardiologic profile according to the different chromosomal patterns and long-term clinical follow-Up of 136 nonpreselected patients. AB - The preferential association between Turner's syndrome and congenital heart defects (CHD) have been well known since the first description by Morgagni. There are few studies about the different cardiologic problems stemming from different chromosomal patterns of X monosomies. We reviewed a large series of 136 patients with Turner syndrome without cardiologic preselection, 29 of whom had some kind of CHD (21.5%). Partial anomalous pulmonary venous drainage (PAPVD; 2.9%), aortic valve disease (stenosis and/or incompetence) (AoVD; 5. 1%), aortic coarctation (AoCo; 4.4%), and bicuspid aortic valve (BicAo; 14.7%) are much more frequent in Turner's syndrome than in the normal population, with the difference being statistically highly significant. In our cases, only the 45, X subjects showed severe CHD and multiple lesions, whereas the X-ring pattern was associated with an elevated prevalence of BicAo. Patients with X-deletion showed no signs of congenital heart malformations. Eleven patients, all with 45, X pattern, and significant CHD, underwent cardiac surgery at a mean age of 7.7 +/- 5.3 years (range 7 days-18 years) without complications. At follow-up of 3-18 years (8.6 +/ 5. 2), we were unable to observe any type of evolution of the remaining untreated cardiovascular anomalies. PMID- 9986887 TI - Complement activation, cytokines, and adhesion molecules in children undergoing cardiac surgery with or without cardiopulmonary bypass. AB - The effect of cardiopulmonary bypass (CPB) on various blood parameters in children undergoing major cardiovascular surgery was investigated in a prospective clinical study. Blood samples of children with CPB (CPB group, n = 18) or without CPB (control, n = 12) were collected before, during, and after surgery. The concentration of routine laboratory parameters, components of the complement system (C3, C4, C5, C1 inhibitor, total hemolytic complement, C3d, and C5a), circulating interleukins (IL-6 and IL-8) and soluble adhesion molecules (sICAM-1 and sE-selectin) were determined. In both groups of patients the serum concentrations of C3, C4, C5, and C1 inhibitor were significantly affected by the treatments (p < 0.001), decreased immediately after onset of anesthesia, were minimal during surgery, and increased thereafter. No significant differences in the kinetics of these parameters were detectable between CPB and control group. In the CPB group the activation of the alternative pathway (increased C3d) was found to be a specific response (p = 0.005), but also in the control group C3d and C5a concentration increased significantly (p < 0.022), indicating complement activation. None of the effects that would be expected after activation of the complement system were specific for the CPB group. In both groups the serum levels of IL-6 increased dramatically during and/or after surgery (p = 0.001), and IL-8 was detectable after surgery in 10/12 control patients. The concentration of sICAM-1 and sE-selectin decreased during surgery (p < 0.04) and later did not increase above baseline. Our data suggest that increased serum levels of inflammation mediators and increased consumption of complement and adhesion molecules occur during cardiovascular surgery. Although complement activation and ICAM-1 consumption are more pronounced in the CPB patients, none of these changes occurs exclusively in the CPB group. We conclude, therefore, that these changes are the combined effect of anesthesia, surgical trauma, and endothelial lesions. Additional, undefined CPB-induced reactions may also contribute the postoperative morbidity. PMID- 9986888 TI - Transcatheter occlusion of residual patent ductus arteriosus after surgical ligation. AB - The reported frequency of residual leaks after surgical ligation of patent ductus arteriosus (PDA) varies from 6% to 23%. Reports on percutaneous closure of PDA also involve patients with residual PDA after ligation, but specific data regarding this type of PDA are rare. Our objective was to assess retrospectively the characteristics of residual PDA relevant to transcatheter closure and occlusion results using three types of occluders. Twelve consecutive patients underwent transcatheter occlusion of residual PDA after surgical ligation at a median age of 4.6 years (range 3. 2-44.6 years) and median weight 16.5 kg (range 13-62 kg). Three types of occluder were used: Gianturco coils, detachable Cook PDA coils, and the new Amplatzer duct occluder. The median diameter of residual PDA after ligation was 1.5 mm (range 0.9-4.2 mm). All PDAs were of type A morphology. Thirteen devices were successfully placed in the 12 patients, without embolization. There were no complications. At 1 month and 1 year follow-up all residual shunts were completely closed. Coils are particularly suitable for complete closure of residual leaks after surgical ligation of PDA. A 100% closure rate was achieved with a low number of implanted coils. PMID- 9986889 TI - Neonatal cardiac catheterization: A 10-year transition from diagnosis to therapy. AB - To assess the changing role of cardiac catheterization in the care of the neonate, a retrospective review of all catheterizations between January 1984 to December 1985 (group I) and January 1994 to December 1995 (group II) at C.S. Mott Children's Hospital was performed. Neonatal cardiac catheterization was performed more frequently (p = 0.02) in group I, comprising 14% (110 of 772) of all catheterizations versus 11% (93 of 880) in group II. Access was performed by cutdown in 15 patients (13 venous and 2 arterial), all in group I. In group I, 20 of 110 patients (18%) had balloon atrial septostomies; no other catheter interventions were performed. Interventions were more frequent (p = 0.003) and varied in group II, including 15 septostomies, 17 balloon valvuloplasties (13 pulmonary and 4 aortic), 2 coil embolizations of collaterals, and 1 cardiac biopsy. Despite the higher prevalence and complexity of interventions in group II, fluoroscopy times (median; range: 16 min; 2-55 vs 16 min; 1-107) were similar in both groups (p = not significant) as well as the prevalence of complications. Neonatal cardiac catheterizations are performed less frequently than they were a decade ago at our institution, and therapeutic interventions have become more common. Despite these changes, fluoroscopy time and the rate of complications have not increased. PMID- 9986890 TI - Tetralogy of Fallot in a patient with Killian-Pallister syndrome. AB - Killian-Pallister syndrome is a rare dysmorphic condition characterized by specific clinical manifestations and tetrasomy 12p. Although the association of this condition with congenital heart disease has been previously documented, no cases have been reported in association with Fallot's tetralogy. We report one such case. PMID- 9986891 TI - Tetralogy of Fallot with levoatrial cardinal vein. AB - A levoatrial cardinal vein is a rare congenital anomaly of the systemic veins. It is frequently associated with left-side obstructive anomalies. We report a case of tetralogy of Fallot with a levoatrial cardinal vein. The innominate vein was absent and two left upper pulmonary veins connected to this vein. There were no left-side obstructive anomalies. PMID- 9986892 TI - Kawasaki disease complicated by peripheral gangrene. AB - An 8.5-month-old male infant with Kawasaki disease (KD) received high-dose intravenous immunoglobulin (IVIG) therapy on the fifth day after fever onset. However, multiple peripheral limb ischemias occurred 2 days later. Accordingly, heparin followed by dipyridamole was administered. Aside from a small amputation at the tip of the right middle finger, all other digital ischemias resolved. This presentation demonstrates that early recognition and management of peripheral gangrene in KD may keep its sequela to a minimum. PMID- 9986893 TI - Radiofrequency catheter ablation of right ventricular outflow tract tachycardia in a preschooler. AB - A 3-year-old girl presented with a febrile illness complicated by right ventricular outflow tract tachycardia, which persisted after resolution of the presumed viral infection. The tachycardia was intermittent, but was significantly exacerbated by exercise. Radiofrequency ablation (RFA) of the ectopic focus was successfully performed and the child remains free of tachycardia 12 months later. A review of the literature suggests that RFA in children is increasingly seen as a safe and convenient option for the treatment of supraventricular tachycardia, whereas the management of ectopic ventricular tachycardia in pediatric practice has not been well defined. PMID- 9986894 TI - Balloon valvuloplasty of critical pulmonary valve stenosis in a premature neonate. AB - Balloon dilatation of critical pulmonary valve stenosis in neonates with a weight of less than 2.5 kg is associated with specific problems, including temperature loss during the procedure, venous access, and problems related to the small size of the cardiac structures. We report our experience with balloon valvuloplasty in a premature newborn weighing 1.22 kg. Venous access was gained with a 4 French sheath, and balloon dilatation was performed with a 3.5 French 7-mm balloon catheter. Temperature loss of the baby was avoided by puncturing the femoral vein prior to the procedure on a neonatal open care system, wrapping the child in cotton, and covering the extremities with aluminium foil. The good result in our patient demonstrates that balloon valvuloplasty is a therapeutic option for treatment of critical pulmonary stenosis in premature infants. PMID- 9986895 TI - Massive biatrial myxomas in a child. AB - Cardiac myxomas are rarely diagnosed in children, and biatrial tumors are an unusual presentation in any age group. An 8-year-old boy with massive biatrial cardiac myxomas, who presented in acute cardiogenic shock with no preceding cardiac symptomatology, is reported. PMID- 9986896 TI - Obstructed infracardiac total anomalous pulmonary venous connection in an adult. AB - Adult survival in patients with uncorrected obstructed infracardiac total anomalous pulmonary venous drainage has not been reported. A 17-year-old man who presented to us with features of severe pulmonary arterial hypertension was diagnosed to have obstructed pulmonary venous drainage to the hepatic vein. Presence of a large ventricular septal defect in this patient may have contributed favorably to survival. PMID- 9986897 TI - Acute inferior cardiac inflow obstruction resulting from inadvertent surgical closure of a prominent Eustachian valve mistaken for an atrial septal defect. AB - A 5-month-old boy with a VACTERL syndrome underwent cardiac surgery for correction of a common arterial trunk and closure of an atrial septal defect. A prominent Eustachian valve was mistaken for the atrial septum and surgically closed. Thirty months later, after gradual shrinking of the foramen ovale with associated reduction of the right-to-left shunt, the boy presented with acute symptoms of a lower inflow obstruction, characterized by hepatomegaly and engorged abdominal vein pattern (Medusa's head). The boy was reoperated successfully after the condition had been recognized. PMID- 9986898 TI - Neonatal ductus arteriosus aneurysm causing nerve palsies and airway compression: surgical treatment by decompression without excision. AB - A 4-kg male child, born at 34 weeks to a gestational diabetic mother, had a large ductus arteriosus aneurysm causing phrenic and recurrent laryngeal nerve palsies and large airway compression. The right and left atrial appendages and distal descending aorta were cannulated, allowing left heart partial or complete cardiopulmonary bypass as necessary. On bypass the ductus was ligated, decompressed, and oversewn but not excised. Examination 1 month later suggested resolution of the recurrent laryngeal palsy and echocardiography showed regression of the aneurysm. Ductus ligation and decompression was an effective surgical treatment, which is less likely to cause complications than resection. PMID- 9986899 TI - Successful treatment of postoperative right ventricular heart failure with the HIA-Medos-assist system in a 2-year-old girl. AB - One year after total correction of tetralogy of Fallot, reoperation was performed in a 2-year-old infant because of an aneurysm of the right ventricular outflow tract. After removal of the aneurysm, massive right ventricular failure occurred. Maximal medical inotropic support could not reestablish sufficient right ventricular function. Therefore, it was decided to implant the new HIA-Medos system as a right ventricular assist. In the postoperative period, echocardiographic controls showed increasing contractility of the right ventricle. The assist system was removed after 3 days and the infant was discharged in good condition on the 22nd postoperative day. PMID- 9986900 TI - The wandering pacemaker: intraperitoneal migration of an epicardially placed pacemaker and femoral nerve stimulation. AB - A premature child with congenital complete heart block had an epicardial single chamber pacemaker implanted at 2 days of age. At 21 months of age, while sitting or standing, the patient's right anterior thigh muscles contracted at her pulse rate. Surgical exploration revealed a free-floating pacemaker in her peritoneum. A new dual-chamber pacemaker was implanted into the abdominal wall with resolution of the child's symptoms. PMID- 9986901 TI - Double-lumen aortic arch by persistence of fifth aortic arch: A new case associated with coarctation. AB - A coarctation of aorta with double-lumen aortic arch due to persistence of an embryonic fifth aortic arch was recognized in a 13-day-old girl and successfully repaired using enlargement of the aorta by side-to-side anastomosis of the fourth and fifth aortic arches. PMID- 9986902 TI - Combination of rare systemic venous anomalies in a child with ventricular septal defect. PMID- 9986905 TI - Upcoming events in pediatric cardiology PMID- 9986904 TI - From other journals PMID- 9986903 TI - Low-dose sotalol in pediatric arrhythmia therapy. PMID- 9986906 TI - Growth hormone and a partial mediator of its biological action, insulin-like growth factor I. AB - This review summarizes data on two hormones, growth hormone (GH) and insulin-like growth factor I (IGF-I). Genes encoding these hormones are actively expressed in various tissues which can synthesize and secrete the corresponding hormones into the intracellular space and blood. Apart from the pituitary, GH gene is also expressed in mammary gland, thymus, spleen, lymph nodes, and blood cells. GH activates expression of the gene of IGF-I and stimulates its secretion by the liver, adipose tissue, thymus, and other tissues. The growth-stimulating effect of GH is mediated (at least partially) by IGF-I, but direct (IGF-I-independent) influence on target tissues is also possible. Genes encoding GH and IGF-I receptors are expressed in all organs and tissues, including various cells of the immune system. GH and IGF-I regulate the function of the immune system via endocrine, paracrine, and autocrine mechanisms. PMID- 9986907 TI - Termination of translation in eukaryotes: new results and new hypotheses. AB - Important new results obtained in studies of prokaryotic and eukaryotic translation termination during 1994-1998 are reviewed. Properties of the newly discovered factors RF3, eRF1, and eRF3 are described. Similarity and difference between prokaryotic and eukaryotic systems of translation termination and recent models of molecular mechanisms of protein synthesis at the termination stage are discussed. Hypotheses concerning the biological role of eRF3 are formulated and discussed. PMID- 9986908 TI - Affinity purification of Alu-DNA-repeat-binding proteins from human somatic cells. AB - A 66-kD Alu-DNA-repeat binding protein was identified in human somatic cell nucleoplasm. Gel shift assay, southwestern blotting, and affinity purification on DNA attached to a carrier were used. A 60-kD protein copurified with the 66-kD protein during affinity purification, probably due to protein--protein interactions. The gel shift assay reveals multiple complexes with exponential dependence of their relative mobility. The short binding site of the 66-kD protein was defined with the help of synthetic oligonucleotides. It is localized between the A and B boxes of RNA polymerase III promotor and is the same as that reported for the Alu-binding protein from human spermatozoids. The same short binding site, the similarity of the isolation procedure from germ and somatic cells, and similar binding properties and molecular masses suggest homology of the two proteins. The relationship of the proteins we studied and the Alu-DNA binding proteins described in the literature is discussed. PMID- 9986909 TI - Lucigenin as a substrate of microsomal NAD(P)H-oxidoreductases. AB - NADPH oxidation and cytochrome c reduction with and without lucigenin as well as NAD(P)H/lucigenin-dependent chemiluminescence of rat liver microsomes were studied. An increased rate of NADPH oxidation and cytochrome c reduction in the presence of lucigenin was related to one-electron lucigenin reduction by microsomal NADPH reductases. The apparent Michaelis constant values for lucigenin (Km appLuc) were 3.6 and 5.0 microM in normoxygenic (pO2 = 150 +/- 5 mm Hg) and 8.7 and 8.3 microM in hypoxygenic (pO2 = 45 +/- 4 mm Hg) media in the reactions of lucigenin-dependent NADPH oxidation and cytochrome c reduction, respectively. The maximal level of NADPH/lucigenin-dependent chemiluminescence was registered at lucigenin concentration close to the mean K Luc/m app in the lucigenin reductase reaction. Increasing the lucigenin concentration from 5 to 100 microM was associated with a decrease in the chemiluminescence intensity; this could be due to the inactivation of cytochrome P450. In the presence of superoxide dismutase (SOD), the rate of lucigenin-dependent cytochrome c reduction and NADPH/lucigenin-dependent chemiluminescence were decreased by 10 and 30%, respectively. The addition of lucigenin to microsomes which contain the reduced hemoprotein--CO complex was followed by the disappearance of the differential absorption spectrum specific for the carboxy complex and by increase in chemiluminescence intensity versus the control (without carboxy complex). Thus, lucigenin-dependent chemiluminescence of microsomes may be due to some enzymes including lucigenin reductase (NADPH-cytochrome P450 reductase, NADH-cytochrome b5 reductase), generation of O2-. in the redox cycle of lucigenin radicals, dioxetane formation by (di)oxygenases, and catalytic action of the cytochrome P450 heme on dioxetane decomposition followed by light quantum emission. Thus, lucigenin cannot be used to measure the basal O2-. formation in tissue homogenates with high levels of NAD(P)H-oxidoreductases. PMID- 9986910 TI - Nondenaturing electrophoresis. Fractionating of photosynthetic pigment--protein complexes and blood plasma proteins. AB - Efficient polyacrylamide gel electrophoresis of labile proteins and protein complexes is reviewed. If only 0.001-0.01% SDS is dissolved in the electrode buffers, the detergent does not exhibit denaturing activity and guarantees high quality of electrophoresis. Even the structure and oxygen-producing activity of the labile photosystem PS2 are preserved after electrophoretic separation of photosynthetic pigment--protein complexes from Anacystis nidulans R2 or other cyanobacteria. The overall spectra of absorption or fluorescence of isolated pigment--protein complexes are equal to the corresponding spectra of the photosynthetic membrane. The distribution of chlorophyll molecules between the components of the photosynthetic apparatus coincides in spectral analysis data and gel fraction densitometry. More than 15 electrophoretic fractions of pigment- protein complexes of chloroplasts from green algae and higher plants were observed including some fractions of PS1, some spectrally different forms of light harvesting pigment--protein complexes, and their oligomers. High resolving capacity of electrophoresis was demonstrated by separation of plasma proteins. Low denaturing activity and low thermal dissipation of the electrode buffer solution allow the use of large diameter tubes (3.5 and 8 cm) in polyacrylamide gel electrophoresis. The cell destruction time and the membrane dissolving time are minimized. The method of electrophoretic staining of the gels was tested. PMID- 9986911 TI - Secretory immunoglobulins A from human milk possess affinity to oligonucleotides and nucleic acids. AB - The antibody (AB) fraction containing sIgA and IgG was isolated from human milk by Protein A-Sepharose chromatography and was shown to possess affinity to DNA cellulose. Ion-exchange HPLC of these AB on a TSK DEAE-5PW column resulted in the isolation of a fraction containing sIgA and oligonucleotides (ON). Gel-filtration of the AB fraction revealed the presence of ON with length 4-8 nucleotides co isolating with sIgA. sIgA Preparations purified on DEAE-Fractogel and DNA cellulose contained lipids which were phosphorylated in the presence of [gamma 32P]ATP. The affinity of HPLC-purified IgG and sIgA to calf thymus DNA, Escherichia coli DNA and total tRNA, and plasmid DNA was demonstrated. IgG was shown to bind to thymus DNA and E. coli DNA, and sIgA was shown to bind to E. coli DNA and tRNA. Nucleic acids of intestinal microflora are supposed to participate in induction of the secretory immune response. PMID- 9986912 TI - Hydrogen peroxide inhibits the growth of cyanobacteria. AB - H2O2 at concentrations of 10(-5)-10(-4) M suppresses phototrophic growth of Anacystis nidulans and Anabaena variabilis in dialysis culture. The growth of the cyanobacteria resumed after a long adaptation period. In batch cultures, the growth of A. nidulans and A. variabilis was suppressed after one-time addition of 10(-2)and 10(-3)-10(-2) M H2O2, respectively. Inducing intracellular H2O2 formation by adding methylviologen, vitamin K3, or phenazine methosulfate suppresses the growth of both cyanobacteria. The catalase inhibitor salicylic acid suppresses the growth of A. nidulans and A. variabilis at a concentration of 5.10(-3) M. The data suggest an inhibitory effect of H2O2 on the growth of the cyanobacteria. H2O2 is unlikely to serve as an electron donor during photosynthesis. PMID- 9986913 TI - Influence of hydration degree of aerosol OT reversed micelles in heptane on inhibitory effect of gallic acid polydisulfide in peroxidase-dependent oxidation of 3,3;,5,5;-tetramethylbenzidine. AB - Gallic acid polydisulfide (GAPD) inhibits with high efficiency tetramethylbenzidine (TMB) peroxidation at 20 degreesC in reversed aerosol OT (AOT) micelles in heptane with various hydration degrees w0 ranging from 8.3 to 47.2. Like in aqueous medium, the inhibition constant Ki for GAPD is approximately 10(-6) M and decreases with increasing w0 from 15.3 to 25. In AOT micelles with various hydration degree, the initial rates of TMB oxidation catalyzed by peroxidase were determined in the absence of GAPD (v0). Using the dependencies of the induction time of TMB peroxidation on the initial GAPD concentration, the values of the stoichiometric coefficient for inhibition by GAPD (f) were calculated at various hydration degrees of AOT micelles. Increase of hydration degree of AOT micelles is accompanied by a decrease of coefficient f from 30-31 (at low hydration degree) to 11.5-12.5 (at w0 > 30), and this significantly exceeds the f values (2) typical for most known inhibitors. PMID- 9986914 TI - Effects of sulfur dioxide on lichen lipids and fatty acids. AB - Lipids and fatty acids were studied in some lichen species after exposure to 1 ppm of aqueous sulfur dioxide. The changes in lipid composition are specific to the lichen species tested. The exposure of lichens to SO2 resulted in a slight reduction of the total phospholipid content. The amount of betaine lipid diacylglyceryltrimethylhomoserine was increased in Stereocaulon paschale, but the level of this lipid was not changed in Peltigera aphthosa. An increase in fatty acid unsaturation in lichens in response to the effect of SO2 probably has adaptive significance. PMID- 9986915 TI - Kinetic properties of the activator complexes plasmin--staphylokinase and plasmin(ogen)--streptokinase in vitro. AB - Comparative kinetic and electrophoretic study of the interaction of plasminogen (PG) with equimolar concentrations of staphylokinase (SPK) and streptokinase (SK) at 4 and 37 degreesC showed that the PG--SK complex has fibrinolytic and esterase activities, whereas the PG--SPK complex was inactive. Both esterase and fibrinolytic activities were enhanced during the conversion of the PG--SPK complex to the complex of plasmin (PL) with SPK (PL--SPK) at 37 and 4 degreesC, while the PG--SK complex was rapidly converted to the PL--SK complex with higher esterase activity only at 37 degreesC. The catalytic efficiency of Z-Lys-pNP hydrolysis (kcat/Km) by the preformed PL--SPK complex was twofold lower than that in the case of the PL--SK complex. Incubation of the PL--SPK and PG--SK(PL--SK) complexes at 37 degreesC for 24 h was associated with the degradation of the proteins and with different kinetics of lowering of esterase, plasminogen activator, and fibrinolytic activities. The PL--SPK complex was considerably more stable than the PG--SK(PL--SK) complex; streptokinase degraded more rapidly than staphylokinase. Kinetics of lysis of fibrin clots by the two complexes were similar, but the efficiency of lysis of plasma clots by the PL--SPK complex was significantly higher than that in the case of the PG--SK(PL--SK) complex (at 0.03 1 microM). Probably, unlike streptokinase, staphylokinase which is less susceptible to degradation in the PL--SPK complex and is released from the triple complex alpha2-antiplasmin--PL--SPK, forms a potentially highly active new complex with free molecules of plasminogen in the plasma. PMID- 9986916 TI - Lipid peroxidation in experimental ischemia of the brain. AB - Lipid peroxidation was studied in the brain of Mongolian gerbils under conditions of complete ischemia followed by recirculation in the left hemisphere without recirculation in the right hemisphere. Thiobarbituric acid reactive products and the intensity of Fe2+-induced chemiluminescence were determined. The content of lipid peroxidation products in the brain tissue was increased not only under conditions of recirculation, but also at the ischemia stage during the limited access of oxygen. Thus, the destructive effect of free radicals may occur even during the early stage of ischemic injury of the brain. PMID- 9986917 TI - Purification and some properties of thymidilate kinase from sea urchin. AB - Thymidilate kinase (EC 2.7.4.9, ATP:dTMP phosphotransferase) was isolated from eggs of the sea urchin Strongylocentrotus intermedius. The enzyme preparation was purified by 1073-fold and was not contaminated with phosphatase or ATPase. The molecular weight of the sea urchin thymidilate kinase is 100 kD, and the pH optimum of its action is 8-8.5. The thymidilate kinase activity is maximal in the presence of 2-5 mM ATP and 10 mM MgCl2. In the reaction of phosphorylation with dTMP, Mg2+ can be partially substituted by other bivalent metal ions whose efficiency decreases in the series: Mg2+ > Mn2+ > Ca2+ = Cd2+ = Co2+. In the presence of Zn2+, Fe2+, Cu2+, and Pb2+ the thymidilate kinase is inactive. The sea urchin thymidilate kinase can utilize ATP, dCTP, and dTTP as donors of the phosphate group. Either dTMP or dCMP can serve as the acceptor of phosphate. Addition of thymidine and other nucleosides to the reaction medium has virtually no effect on the rate of dTMP phosphorylation. PMID- 9986918 TI - Reduction of nitrite by glycosylated amino acids and glycosylated albumin. AB - Glycosylated amino acids and glycosylated human serum albumin reduce nitrite to nitric oxide under anaerobic conditions. The amount of nitric oxide produced was recorded by generation of nitrosoHb from deoxyHb. Without preincubation after the addition of sodium nitrite, glucose or a mixture of glucose with amino acid or serum albumin did not cause spectrophotometrically detectible transformation of deoxyHb into nitrosoHb. The generation of NO increased with an increase in content of colored "final" products of amino acid and serum albumin glycosylation in the incubation mixture. The incubation of blood plasma of patients with diabetes mellitus with nitrite also resulted in the increased production of NO as compared to blood plasma of healthy subjects. During the incubation of healthy subjects' blood plasma with nitrite a small amount of NO was produced. The removal of low-molecular-weight compounds was accompanied by a significantly decreased generation of NO by blood plasma. PMID- 9986919 TI - Role of soluble guanylate cyclase in reactivation of choline esterase inhibited by phosphoorganic compounds. AB - The effects of possible activators of soluble guanylate cyclase were studied. Hydroxylamine and some oxime derivatives such as pyridinium aldoximes and bispyridinium dioxime (dipyroxime) were tested as possible guanylate cyclase activators. These compounds are known to be reactivators of choline esterase which has been preinhibited with phosphoorganic compounds. All the tested compounds were found to activate human platelet guanylate cyclase in the concentration range 10-6-10-3 M. The highest stimulatory affect was achieved at 10-4 M with hydroxylamine and dipyroxime: 210 +/- 10 and 320 +/- 15%, respectively. Potassium ferricyanide oxidation of these compounds under mild conditions formed nitroprusside ion, as registered by the electrochemical (polarographic) method; this is evidence that these compounds are NO donors. It is concluded that the activation of guanylate cyclase by the tested compounds is associated with their ability to generate NO during their biotransformation. The possible role of guanylate cyclase activation by oxime derivatives in the mechanism underlying the reactivation of inhibited choline esterase at the cell level is discussed. PMID- 9986920 TI - Acute intrahippocampal injection of human interleukin-1beta stimulates the anterior pituitary POMC transcription and increases plasma levels of ACTH and corticosterone in the male rat. AB - It has been well documented that interleukin-1beta (IL-1beta) is a major mediator for recruiting the hypothalamo-pituitary-adrenal (HPA) axis following infectious disease. The recent localization of IL-1beta receptors in neurons of the hippocampus provides further support for the role of IL-1beta as a neurotransmitter/neuromodulator in the central nervous system. In this study, we investigated whether an acute intrahippocampal injection of IL-1beta is able to rapidly stimulate HPA activity. Seven days after bilateral implantation of a guide cannula into the hippocampus, human IL-1beta (10 ng/0.5 microliter/side) was injected to freely moving male rats. Following this, animals were sacrificed at times 20, 45 and 90 min postinjection and a kinetic analysis of hIL-1beta action on plasma ACTH and corticosterone (CORT) concentrations and nuclear processing of the anterior pituitary (AP) proopiomelanocortin (POMC) was conducted. Intrahippocampal administration of hIL-1beta significantly increased both plasma ACTH and CORT concentrations at 45 and 90 min postinjection. This increase in ACTH concentration paralleled a rise in AP POMC gene transcription. Moreover, the increase in AP POMC primary transcript was followed by an increase in AP POMC intermediate processing RNA. However, at these times, no significant hIL-1beta effect on the level of AP nuclear POMC mRNA was observed. Almost identical results were obtained after intraperitoneal injection of hIL-1beta. In conclusion, our data demonstrates that the hippocampal IL-1beta/IL-1beta receptor is directly and rapidly implicated in HPA activation, in the same manner as that observed after intraperitoneal administration of hIL-1beta. These results show that IL-1 action in the hippocampus could be of immunoneuroendocrine significance for the HPA axis activation during inflammatory states. PMID- 9986921 TI - Hyporesponsiveness of the pituitary to CRH during slow wave sleep is not mimicked by systemic GHRH. AB - During slow wave sleep (SWS) pituitary responsiveness to CRH is reduced. Since GHRH is involved in the promotion of SWS in humans and rats, it was examined whether the blunted CRH-induced ACTH and cortisol release during SWS could be mimicked by systemic GHRH. Young healthy men (n = 7) participated in 4 sleep endocrine protocols: (A) lights off at 23.00 h, intravenous injection of 50 microgram CRH during the first SWS period; (B) lights off at 01.00 h, injection of 100 microgram GHRH at 23.00 h, followed by 50 microgram CRH at 23.30 h; (C) lights off at 01.00 h, injection of 50 microgram CRH at 23.30 h, and (D) lights off at 23.00 h, saline treatment only (= baseline condition). The sleep EEG was recorded during the lights off period and blood samples, collected every 20 min between 22.00 and 07.00 h, were assayed for GH, cortisol and ACTH. There was no significant difference in the sleep-associated GH peak between protocols. Plasma ACTH was significantly higher following CRH administration during wakefulness compared with CRH administration during SWS (protocols B and C vs. A; area under the curve (AUC) 23. 00-03.00 h: 9.6 +/- 4.8 and 7.3 +/- 2.0 vs. 6.1 +/- 1.1 ng/ml x min; p < 0.05), while there was no significant difference in plasma ACTH concentration between the baseline condition and protocol A (CRH administration during SWS). Similarly, cortisol was significantly enhanced compared with baseline following CRH during wakefulness only. CRH induced an increase in EEG activity in the sigma frequency range, both when it was administered during wakefulness and SWS, while this effect was reduced by pre-treatment with GHRH. In summary, our data suggest that (1) the blunted CRH-induced release of ACTH and cortisol during SWS is not mimicked by systemic GHRH administration, and (2) CRH enhances sigma EEG activity possibly via modulation of afferent pathways from the median eminence to the thalamus and this effect is reduced by pre-treatment with GHRH. PMID- 9986922 TI - The role of the retrochiasmatic area in the control of pineal metabolism. AB - The aim of the present investigation was to study the effect of neurotoxic ibotenic acid lesion of the retrochiasmatic area on the daily profile of pineal N acetylserotonin and melatonin synthesis and on the pineal metabolic reactivity to nocturnal short-term retinal photostimulation. Groups of rats were killed 6 h after lights off either in the dark of immediately after being photostimulated for 1 or 15 min. Additionally, groups of rats were sacrificed at six different time points throughout the 24-hour light-dark cycle. The results suggested the presence of two functionally distinct territories in the retrochiasmatic area. The basal retrochiasmatic area, an area situated immediately ventral to the third ventricle, behind the suprachiasmatic nuclei and in front of the arcuate nucleus, is implicated in the nocturnal inhibitory process induced by short-term retinal photostimulation. The lateral retrochiasmatic area, which is situated immediately lateral to the anterior periventricular nucleus, below the anterior hypothalamic nucleus and in front of the ventromedial hypothalamic nucleus, is importantly involved in the control of the peak amplitude of the daily production of N acetylserotonin and melatonin by the pineal gland. PMID- 9986923 TI - Melatonin modulation of the daily prolactin secretion in intact and ovariectomized ewes. Relation to a phase of the estrous cycle and to the presence of estradiol. AB - The aim of this study was to investigate whether melatonin might modulate the daily prolactin secretion in the ewe during a period of ovarian activity and, if so, whether this modulatory action of melatonin was related to the presence of estradiol in the organism. Ewes in the late follicular and luteal phase, as well as overiectomized ewes without (OVX) and after 7 days of estradiol injections (OVX+E2) were examined. Melatonin was infused into the third brain ventricle (100 microgram/100 microliter/h) from 14.00 to 18.00 h. The concentration of prolactin increased significantly during the infusion of melatonin in late follicular-phase ewes, but not in luteal-phase ewes, as compared to the concentration before the infusion: range from 204.0 +/- 31.7 to 272.2 +/- 50.1 ng/ml vs. range from 68.2 +/- 31.8 to 94.7 +/- 33.1 ng/ml (mean +/- SEM, n = 4, p < 0.01) and to the concentration noted during control infusions: range from 130.0 +/- 58.0 to 179.3 +/- 55.6 ng/ml (mean +/- SEM, n = 4, p < 0.05). In ovariectomized ewes, the concentration of prolactin during infusion of melatonin increased significantly, unrelated to the presence of estradiol, as compared to the concentration before infusion: range from 136.7 +/- 20.3 to 260.0 +/- 11.6 ng/ml vs. range from 41.6 +/- 2.6 to 152.3 +/- 14.6 ng/ml in OVX ewes (mean +/- SEM, n = 4, p < 0.01) and range from 161.5 +/- 66.5 to 250.2 +/- 24.3 ng/ml vs. range from 61.2 +/- 1.7 to 159.2 +/- 43.3 ng/ml in OVX+E2 ewes (mean +/- SEM, n = 4, p < 0.01). Concentrations during infusion of melatonin in OVX and OVX+E2 ewes were also significantly higher than during the control infusions: range from 7.2 +/- 1.7 to 22.2 +/- 4.1 ng/ml (mean +/- SEM, n = 4, p < 0.001). These results indicate that melatonin may affect the daily secretion of prolactin in ewes during the breeding season, and suggest that the variable response of prolactin to the melatonin signal in intact and ovariectomized ewes relates to the interaction between both ovarian steroids - estradiol and progesterone - and the prolactin-releasing factor. PMID- 9986924 TI - Binding of the non-peptide vasopressin V1a receptor antagonist SR-49059 in the rat brain: an in vitro and in vivo autoradiographic study. AB - A potent non-peptide vasopressin (AVP) antagonist, SR-49059, displaying high stability and selective affinity for the V1a AVP receptor subtype, has recently been described. The objective of this study was to assess the binding properties and the penetrability of this compound in the rat brain. Both in vitro and in vivo binding autoradiography experiments were performed. In all studies, the liver was used as a reference V1a tissue. In vitro labelling of rat brain sections with [3H]SR-49059 was similar to that previously detected with [3H]AVP, which confirms that the majority of central AVP binding sites are V1a sites similar to peripheral V1a receptors. As expected, intense specific labelling occurred mainly in the lateral septum, the fundus striatum, the hypothalamic stigmoid nucleus and the area postrema-nucleus of the solitary tract complex. In vivo binding autoradiography showed that [3H]SR-49059 injected intravenously did not enter the brain parenchyma. Specific labelling was however clearly detectable in brain regions with permeable hematoencephalic barrier, the choroid plexus and other circumventricular organs expressing V1a receptors, namely the subfornical organ, the pineal gland and the area postrema. The specificity of [3H]SR-49059 binding in the latter structures was confirmed by the fact that labelling was prevented by pretreatment of animals with high doses of nonradioactive SR-49059. In conclusion, our study shows that [3H]SR-49059 is a suitable probe to investigate V1a receptors in the rat brain. We also demonstrate that although this compound is not able to enter the brain tissue from the peripheral circulation, it does bind specifically to regions devoid of blood-brain barrier and known to be involved in autonomic regulations. PMID- 9986925 TI - Effect of serotonin inhibition on glucocorticoid and mineralocorticoid expression in various brain structures. AB - Many studies have shown the existence of functional interactions between central neurotransmitter systems and the hypothalamo-pituitary adrenal axis. Mineralocorticoid receptors (MR) and glucocorticoid receptors (GR) are regulated by multiple factors including glucocorticoids themselves. Neurotransmitters such as serotonin (5-hydroxytryptamine: 5-HT) can regulate brain corticosteroid receptors in a complex way. The present study examined the short-term (48 h) effects of parachlorophenylalanine (PCPA), a drug which specifically inhibits 5 HT synthesis, on corticosteroid receptor levels and on the expression of their respective messenger ribonucleic acids (mRNA) in the rat hippocampus, hypothalamus and brain stem. The study was performed in bilaterally adrenalectomized animals, in order to avoid potential drug-induced changes in plasma corticosterone levels, which could secondarily regulate MR and GR. Short term inhibition of 5-HT synthesis by PCPA significantly increased the number of hippocampal MR-binding sites. PCPA treatment did not alter the number of GR binding sites in the hippocampus, hypothalamus and brain stem. We observed no change in the affinities of GR and MR sites in all the structures studied. In PCPA-treated rats, restoration of control 5-HT levels by injection of its immediate precursor, 5-hydroxytryptophan (5-HTP) brings the number of hippocampal MR-binding sites back to control levels. It can therefore be concluded that the increase in number of MR-binding sites induced by acute PCPA treatment is dependent on the decrease in 5-HT levels. The increase in hippocampal MR binding sites was correlated with an induction of their messengers, suggesting that 5-HT modulates the synthesis of MR protein. Although PCPA did not modify the number of hippocampal GR-binding sites, a decrease in hippocampal GR mRNA expression was observed. This study shows that 5-HT inhibits hippocampal mineralocorticoid receptor synthesis and that this effect is not mediated by changes in corticosterone hormone secretion, and illustrates the existence of complex mechanisms for corticosteroid receptor regulation in the hippocampus. PMID- 9986926 TI - Estrogens normalize the hypothalamic-pituitary-adrenal axis response to stress and increase glucocorticoid receptor immuno-reactivity in hippocampus of aging male rats. AB - Aging is associated with a disturbance in the regulation of the hypothalamic pituitary-adrenal axis (HPA) and reduced levels of glucocorticoid receptors (GR) in the hippocampus. To compensate for these effects, we have investigated whether estrogen therapy normalized the HPA response to stress and GR in hippocampus and paraventricular (PVN) nucleus. Young (3-4 months) and old (20 months) male Sprague-Dawley rats were bled by tail cut in the basal state and following ether stress. While basal and ether-stimulated levels of plasma corticosterone (CORT) were similar in the two groups, old animals presented a delayed termination of the response to ether stress. A dexamethasone inhibition test carried out in old animals, showed a failure to completely block plasma CORT after ether stimulation. Furthermore, in old rats GR-immunoreactive levels were reduced in CA1-CA2 hippocampal subfields and subiculum, while normal levels were obtained in CA3-CA4 and PVN. We observed that prolonged estrogen treatment (6 weeks) of old rats normalized the termination of the stress response, restored dexamethasone inhibition of plasma CORT, and increased GR immunoreactivity in CA1 and CA2 hippocampal subfields and subiculum. The results suggest that estrogen treatment enhanced the glucocorticoid feedback signal by increasing GR in hippocampus, and corrected the disturbances in HPA axis regulation. These animal experiments may be important to elucidate the effects of estrogenic on the hippocampal and HPA dysfunction associated with aging and Alzheimer's disease in humans. PMID- 9986928 TI - Erratum: Transport near the metal-insulator transition: Polypyrrole doped with PF6 PMID- 9986927 TI - In vivo characterization of 11beta-hydroxysteroid dehydrogenase in rat hippocampus using glucocorticoid neuroendangerment as an endpoint. AB - 11beta-Hydroxysteroid dehydrogenase (11beta-HSD) is the enzyme responsible for the interconversion of corticosterone (CORT) to 11-dehydrocorticosterone (11 DHC). CORT is an adrenal hormone secreted during the stress response and it has widespread effects in many different target tissues. In addition, CORT can exacerbate damage caused by neurological insults, such as kainic acid-induced seizures. In addition to its protective role in the kidney, 11beta-HSD is also thought to play a role in steroid regulation in the brain. However, it is not known whether the enzyme is acting in vivo as a reductase or a dehydrogenase. If the enzyme is working as a reductase, converting 11-DHC to CORT, it has the potential to exacerbate neurotoxicity due to other agents. On the other hand, 11beta-HSD could be neuroprotective if the enzyme is acting as a dehydrogenase, deactivating CORT by converting it into 11-DHC. To characterize the enzyme in vivo, we have utilized glucocorticoid neuroendangerment in the hippocampus as an indirect assay of 11beta-HSD function. We have shown that 11-DHC can exacerbate kainic acid toxicity in adrenalectomized (ADX) rats and this exacerbation is blocked by the 11beta-HSD antagonist, carbenoxolone; these findings suggest that 11beta-HSD is working as a reductase in ADX rats. The presumptive reductase activity found in ADX rats was derived from both hippocampal and peripheral forms of the enzyme. In the presence of physiological levels of glucocorticoids, reductase activity was decreased and no dehydrogenase activity was detected. The present study demonstrates that 11beta-HSD reductase activity, both in vivo and in vitro, occurs only in the presence of low levels of circulating glucocorticoids. PMID- 9986929 TI - Erratum: Electronic-band parameters in strained Si1-xGex alloys on Si1-yGey substrates PMID- 9986930 TI - Erratum: Studies of ac hopping conduction at low temperatures PMID- 9986931 TI - Erratum: Effects of band nonparabolicity and central-cell corrections on the spectrum of Si donors in GaAs quantum wells PMID- 9986932 TI - Erratum: Prediction of giant chi (3) values from a calculation of excitonic nonlinear optical properties in rectangular GaAs quantum-well wires PMID- 9986933 TI - Erratum: First-principles molecular-dynamics simulation of liquid Li12Si7 PMID- 9986935 TI - Erratum: Core-cancellation functions for evaluating exchange-correlation functions in first-principles pseudopotential calculations PMID- 9986934 TI - Erratum: Stretched-exponential decay of the luminescence in porous silicon PMID- 9986936 TI - Erratum: Spherical voids in the stabilized jellium model: Rigorous theorems and Pade representation of the void-formation energy PMID- 9986938 TI - Erratum: In situ infrared transmission study of Rb- and K-doped fullerenes PMID- 9986937 TI - Erratum: Relativistic band gaps in one-dimensional disordered systems PMID- 9986939 TI - Erratum: Itinerant-electron-type helical-spin-glass reentrant transition in Cr0.81Mn0.19Ge PMID- 9986940 TI - Erratum: Single-band Hubbard model for superconductivity and charge-density-wave order in the bismuth oxide superconductors PMID- 9986941 TI - Erratum: Electron band structure in a two-dimensional periodic magnetic field PMID- 9986942 TI - Erratum: g tensor for substitutional nitrogen in diamond PMID- 9986943 TI - Erratum: Effect of competition between point and columnar disorder on the behavior of flux lines in (1+1) dimensions PMID- 9986944 TI - Erratum: Initial-vortex-entry-related magnetic hysteresis in thin-film SQUID magnetometers PMID- 9986946 TI - Erratum: Pressure-induced kinetics of ferroelectric phase transitions PMID- 9986945 TI - Erratum: Exact exchange-potential band-structure calculations by the LMTO-ASA method: MgO and CaO PMID- 9986947 TI - Erratum: Field-induced transfer of an atom between two closely spaced electrodes PMID- 9986948 TI - Erratum: Auger intra-atomic transitions in grazing atom-surface collisions PMID- 9986949 TI - Erratum: Valence-electron distribution of cesium crown-ether electrides PMID- 9986950 TI - Erratum: Inelastic-phonon-scattering effect on the behavior of the thermoelectric power of metals PMID- 9986951 TI - Erratum: Simple model for multistability and domain formation in semiconductor superlattices PMID- 9986952 TI - Erratum: Quantum-dot ground states in a magnetic field studied by single-electron tunneling spectroscopy on double-barrier heterostructures PMID- 9986954 TI - Erratum: Resistivity as a function of temperature for models with hot spots on the Fermi surface PMID- 9986953 TI - Erratum: Cluster study of the neutron-scattering form factor for antiferromagnetic KNiF3 and NiO PMID- 9986955 TI - Erratum: Ion-surface interactions in the electron-stimulated desorption of Cl+ from Cl2/Si(111)-7 x 7 PMID- 9986956 TI - Erratum: Localization, antilocalization, and delocalization in one-dimensional disordered lattices PMID- 9986958 TI - Erratum: Sign reversal of the Hall effect in untwinned single-crystal superconducting YBa2Cu3O7- delta PMID- 9986957 TI - Erratum: Supercooled liquid dynamics for the charged hard-sphere model PMID- 9986959 TI - Erratum: Optical and ESR study of Er3+ in LiNbO3 PMID- 9986961 TI - Erratum: Quantum interference in liquid metals PMID- 9986960 TI - Erratum: Kondo crossover in the self-consistent one-loop approximation PMID- 9986962 TI - Erratum: Simple trial function for shallow donor D0 states in GaAs-Ga1-xAlxAs quantum-well structures PMID- 9986964 TI - Erratum: Magnetotransport properties of La0.6Pb0.4MnO3- delta and Nd0.6(Sr0.7Pb0.3)0.4MnO3- delta single crystals PMID- 9986963 TI - Erratum: Dynamical properties and related optical spectra of fullerenes: The bond charge-model description PMID- 9986965 TI - Erratum: Magnetic penetration depth and condensate density of cuprate high-Tc superconductors determined by muon-spin-rotation experiments PMID- 9986966 TI - Erratum: Interaction of coupled plasmon-phonon modes with a point charge in a polar semiconductor PMID- 9986967 TI - Erratum: Magnetoplasma excitations in quantum-well wires PMID- 9986968 TI - Erratum: Inner-shell promotions in low-energy Li+-Al collisions at clean and alkali-covered Al(100) surfaces PMID- 9986969 TI - Erratum: Rigorous upper bound for the persistent current in systems with toroidal geometry PMID- 9986970 TI - Erratum: Bound on the group velocity of an electron in a one-dimensional periodic potential PMID- 9986972 TI - Erratum: Finite-temperature resonant magnetotunneling in AlxGa1-xAs-GaAs-AlyGa1 yAs heterostructures PMID- 9986971 TI - Erratum: Logarithmic temperature dependence of conductivity at half-integer filling factors: Evidence for interaction between composite fermions PMID- 9986973 TI - Erratum: Enhanced optical properties in porous silicon microcavities PMID- 9986974 TI - Erratum: Superstructures and defect structures revealed by atomic-scale STM imaging of WO3(001) PMID- 9986975 TI - Erratum: Theory of charge transfer at the high-Tc superconductor/electrolyte interface PMID- 9986976 TI - Erratum: Coarsening and slope evolution during unstable epitaxial growth PMID- 9986977 TI - Erratum: Evidence of redistribution of the itinerant holes below Tc in Bi2Sr2CaCu2O8 superconductors: A polarized x-ray-absorption study PMID- 9986979 TI - Erratum: Superconducting phase of a two-chain Hubbard model PMID- 9986978 TI - Erratum: Growth and morphology of ultrathin Fe films on Cu(001) PMID- 9986980 TI - Erratum: Lattice dynamics of skutterudites: First-principles and model calculations for CoSb3 PMID- 9986981 TI - Erratum: Transport properties of Pb-doped Bi4Sr3Ca3Cu4Ox semiconducting glasses and glass-ceramic superconductors PMID- 9986982 TI - Erratum: Probing oscillatory exchange coupling with a paramagnet PMID- 9986983 TI - Erratum: Large and irregular shift of photoluminescence excitation spectra observed in photochemically etched porous silicon PMID- 9986984 TI - Erratum: Anharmonic contribution to the Debye-Waller factor for copper, silver, and lead PMID- 9986985 TI - Erratum: Phi 0/2 vortices in a defect-containing Josephson-junction array PMID- 9986986 TI - Erratum: Aligned carbon-hydrogen complexes in GaAs formed by the decomposition of trimethylgallium during low-pressure metal-organic vapor-phase epitaxy PMID- 9986987 TI - Erratum: Analysis of the x-ray diffuse scattering in C60 from microscopic models PMID- 9986988 TI - Erratum: Effective masses in In1-xGaxAs superlattices derived from Franz-Keldysh oscillations PMID- 9986989 TI - Erratum: Excitation spectrum of the attractive Hubbard model PMID- 9986990 TI - Erratum: Magnetostrictive bending of a film-substrate system PMID- 9986991 TI - Erratum: Grain-boundary dissociation by the emission of stacking faults PMID- 9986992 TI - Environmental skin diseases and the impact of common dermatoses on medical readiness. AB - The environmental extremes in which soldiers exercise and fight, like the environmental extremes in which many civilians encounter occupationally and recreationally, can prove to be a significant cause for morbidity and decreased effectiveness. A variety of skin diseases are related to occupational exposure to dusts and ultraviolet radiation as a well known cause of cutaneous damage. As more is understood about the biochemical factors involved in frostbite injury, treatment recommendations have changed. Too much water, hot or cold, is a continued source of cutaneous misery to the soldier in the field. Finally, even common minor skin ailments can incapacitate the sufferer when confronted with unfavorable environments. PMID- 9986993 TI - Evaluation and management of nonmelanoma skin cancer. The military perspective. AB - As the incidence of melanoma skin cancer continues to increase in this country, so does the need for early detection and treatment of these tumors. This article discusses a military skin cancer screening clinic that encourages patient participation and the criteria and statistics regarding the different treatment modalities we employ to treat these skin cancers. PMID- 9986994 TI - Exotic virus infections of military significance. Hemorrhagic fever viruses and pox virus infections. AB - Military personnel are frequently deployed to distant locations around the world under conditions of great stress, which involve potential exposure to hazardous viruses that are not commonly seen in the developed world. This article will provide an overview of two clinical presentations of viral infections of potential military significance: hemorrhagic fever and poxvirus infections. The three viral hemorrhagic fever viruses described--dengue, hemorrhagic fever with renal syndrome, and Congo-Crimean hemorrhagic fever--represent the diversity of potential hemorrhagic fever viruses that military forces may be exposed. Human poxvirus infections are currently uncommon but knowledge of these agents, will again become important should a terrorist threat of the use of smallpox become real and widespread use of vaccinia be considered to protect the military force. PMID- 9986995 TI - The prevention and treatment of cutaneous injury secondary to chemical warfare agents. Application of these finding to other dermatologic conditions and wound healing. AB - Chemical warfare agents are easily and inexpensively produced and are therefore potentially accessible to even underdeveloped nations and are a threat to civilian populations as well as advancing troops. Sulfur mustard is by far the most significant chemical warfare agent that produces cutaneous injury. Significant advances over the past few years have been made in understanding the pathophysiology of the lesions produced by sulfur mustard, as well as development of barrier creams and pre and post exposure therapies to moderate the damage and accelerate healing. Not only have these advances improved our understanding of the sulfur mustard injury and the care of the patients, these are potentially numerous applications for these findings in other dermatologic conditions including the treatment of chronic wounds. PMID- 9986996 TI - Dermatologists and the burn center. AB - Severe cutaneous disease and injury often is best treated in the specialized treatment environment of a burn center. Skilled burn treatment personnel combine critical care expertise with extensive clinical experience in the management of severe cutaneous injury and disease. In addition to thermal injury, the burn center is the ideal environment for patients with progressive toxic epidermal necrolysis, pemphigoid lesions, and invasive cutaneous infection. Recent research indicates that the burn wound is a dynamic structure whose ultimate extent is modifiable by manipulations of the local anatomic and molecular environment. The many unanswered questions on the pathogenesis and treatment of both the "medical" and "surgical" cutaneous processes require close collaboration between the dermatologist and the burn team. PMID- 9986997 TI - The United States military and leishmaniasis. AB - Leishmaniasis occurs not only in American travelers and military personnel alike but infects a significant portion of the world's population. The US military has made major contributions to the understanding of the complicated epidemiology of this parasite, the development of rapid reliable diagnostic tests, and to the development of safe, more efficient, and more effective treatment of leishmaniasis. PMID- 9986998 TI - Recognition and management of high-risk cutaneous tumors. AB - The majority of cutaneous malignancies can be treated by the military dermatologist in a clinical setting. Recognition of tumors at high risk for recurrence or metastasis is important for any dermatologist but especially list care. Providing optimal care includes knowledge about which patients should be medavacced to larger medical centers for advanced surgical and medical treatments. PMID- 9986999 TI - The history of teledermatology in the Department of Defense. AB - The Department of Defense (DoD) healthcare system supports the medical needs of service members while engaged in a variety of missions frequently in isolated, remote, and austere locations. As a result, the DoD has been a leader in the development of telemedicine, including teledermatology as a way to provide "good medicine in bad places." A brief technical history of teledermatology, representative DoD experiences including military unique concerns, and a novel approach to increase the access of DoD teledermatology consultation are presented in this article. PMID- 9987000 TI - Advanced laboratory techniques at the Armed Forces Institute of Pathology applicable to diagnosis and research in dermatology. AB - The Armed Forces Institute of Pathology (AFIP) is well known for providing expert pathology in many specialties and educational courses for civilian and military personnel. Some of the departments at the AFIP have also developed expertise in various advanced laboratory techniques for diagnosis and research that are applicable to dermatology and are not available at most medical centers. PMID- 9987001 TI - Lasers in the military for cutaneous disease and wound healing. AB - The clinical laser experience of military dermatologists mirrors that of their civilian counterparts; however, there are applications for lasers in dermatology in which there is special military relevance. These range from treatment of common diseases such as pseudofolliculitis barbae to noninvasive identification of shrapnel injuries on the battlefield using novel laser-based diagnostic techniques. Although some applications in this report are experimental, emerging technologies should allow for their clinical or field implementation in the near future. PMID- 9987002 TI - Unusual cutaneous infectious and parasitic diseases. AB - The cutaneous manifestations of thirteen unusual infections and parasitic diseases are described. Their geographic distribution, morphologic features of the causative organism, histopathologic changes, criteria for diagnosis, and treatment are included. PMID- 9987003 TI - The dermatologist's Baedeker. Preparation for medical assistance missions. AB - Dermatologists often participate in medical assistance missions in developing nations, achieving both humanitarian and personal objectives. This term outreach mission abroad and will serve as a guide for preparing oneself, personally and professionally, for the practical and philosophical aspects of humanitarian assistance. It will help one participate in such an endeavor in a safe, comfortable, healthy, productive, and enjoyable manner. PMID- 9987004 TI - The dermatologist in military operations. AB - The military dermatologist has a specific and significant role in military operations--in time of war as well as in peace. Many dermatologists are unfamiliar with the impact that our specialty and cutaneous disease has upon the ability of the military to fulfill the missions, duties, and responsibilities assigned by our government. This article highlights a few of the recent or ongoing types of military operations in which our specialty plays a prominent part. PMID- 9987005 TI - Treatment of diaper dermatitis. AB - Diaper rash therapy can be as simple as A, B, C, D, and E if you are able to identify generic diaper rash and exclude other causes. Components of diaper rash treatment include airing, barrier and other tropical product application, cleansing of the diaper area, diaper selection, and education of caregivers. Diaper rash therapy can be letter-perfect. PMID- 9987006 TI - Differential effects of adenosine receptor subtypes on release and reuptake of hippocampal serotonin. AB - To clarify the effects of adenosine receptor subtypes (A1, A2 and A3) on hippocampal serotonin (5-HT) release and 5-HT reuptake activity, hippocampal extracellular 5-HT levels were determined in vivo by microdialysis in freely moving rats. Selective 5-HT reuptake inhibitor (SSRI) fluoxetine and DU24565 increased extracellular 5-HT levels. Adenosine and A1 receptor agonist, 2-chloro N6-cyclopentyl-adenosine (CCPA), decreased extracellular 5-HT levels, whereas non selective antagonist, caffeine, and A1 antagonist, 8-cyclopentyl-1,3 dimethylxanthine (CPT) increased them. When 5-HT reuptake activity was inhibited by DU24565 and fluoxetine, the effects of CPT and CCPA on 5-HT level were enhanced. A2A receptor agonist, CGS21680, A2 receptor agonist, PD125944, A2 receptor antagonist, 3,7-dimethyl-1-propargylxanthine (DMPX), and A3 receptor agonist, N6-2-(4-aminophenyl)ethyladenosine (APNEA) did not affect 5-HT levels; however, when A1 receptor was blocked by CPT, 5-HT levels were increased by adenosine, CGS21680 and PD125944, and decreased by DMPX and APNEA. Under conditions of A1 receptor blockade, pretreatment with DU24565 or fluoxetine, enhanced the stimulatory effects of CGS21680 and PD125944 as well as inhibitory effects of DMPX on 5-HT level, whereas the inhibitory effect of APNEA was abolished. These results indicate that the stimulatory effects of A2 receptor and inhibitory effects of A3 receptor on hippocampal extracellular 5-HT levels are masked or abolished by the inhibitory effects of A1 receptor. In addition, hippocampal serotonergic transmission might be modulated by hippocampal presynaptic adenosine receptor subtypes, and hippocampal 5-HT reuptake activity might be modulated by hippocampal A3 receptor. PMID- 9987007 TI - Prolonged expression of zinc finger immediate-early gene mRNAs and decreased protein synthesis following kainic acid induced seizures. AB - In the present study in situ hybridization was used to study the effect of kainic acid induced seizures on the expression of the zinc finger immediate-early genes (IEGs) NGFI-A, NGFI-B, NGFI-C, egr-2; egr-3 and Nurr1. Kainic acid markedly induced these IEGs especially in hippocampus, cortex and amygdala by 30 min. This induction gradually decreased and returned to baseline by 24 h in most regions. However, in the CA1 and CA3 subfields of hippocampus known to be damaged by kainic acid the expression of all the IEGs except egr-2 remained elevated for 24 h. NGFI-A, NGFI-B, NGFI-C and to a lesser extent, Nurr1, remained elevated also in the subcortical region of the temporal lobe. By 24 h incorporation of 14C leucine decreased in the piriform cortex, amygdala, and in the CA1 and CA3 subfields, but not in CA2 and dentate gyrus. These areas showing decreased protein synthesis in the hippocampus by 24 h showed prolonged IEG induction, whereas IEG expression returned to control levels in areas showing normal protein synthesis. In the temporal lobe decreased protein synthesis coexisted with decreased IEG expression, whereas areas in the vicinity of the region showing decreased protein synthesis demonstrated elevated IEG expression. The decreased protein synthesis was localized in areas where extensive neuronal death has occurred. This prolonged IEG induction in the hippocampus, which has been linked with neuronal death, could solely represent a prolonged mRNA turnover caused by disrupted protein synthesis. The prolonged IEG expression in the temporal lobe appeared to be localized in regions where the cells are in stress, but still viable. The sustained IEG expression might therefore either represent a stress response by which the neurons are trying to protect themselves or, alternatively, the IEG response may be an early sign indicating that these cells are initiating a pathway leading to programmed cell death. PMID- 9987008 TI - Nicotinic receptors in the rat prefrontal cortex: increase in glutamate release and facilitation of mediodorsal thalamo-cortical transmission. AB - The modulatory influence of nicotinic acetylcholine receptor (nAChRs) on thalamocortical transmission was characterized in the prelimbic area (PrL) of the rat prefrontal cortex. In the first experiment, rats received a unilateral excitotoxic lesion centred on the mediodorsal thalamic nucleus (MD), and were sacrificed 1 week later. The lesion resulted in a 40% reduction of 3H-nicotine autoradiographic labelling in the ipsilateral prefrontal cortex, particularly in areas that are innervated by the MD. Electrophysiological experiments were subsequently performed in non-lesioned anaesthetized animals, in order to study modulation of short- and long-latency responses of PrL neurons evoked by electrical stimulation of the MD. The short-latency responses result from activation of the MD-PrL pathway and are mediated via AMPA-type glutamatergic receptors, whereas the long-latency responses reflect activation of the recurrent collaterals of cortical pyramidal neurons, Iontophoretic application of nicotinic agonists (nicotine, DMPP) facilitated both types of response. Local application of the nAChR antagonists dihydro-beta-erythroidine, mecamylamine and methyllycaconitine, prevented both kinds of facilitation. Finally, intracerebral microdialysis experiments were performed in order to test for nicotinic modulation of extracellular glutamate concentrations in the PrL. Direct application of nicotine via the dialysis probe increased glutamate levels in a dose-dependent manner. This effect was blocked by local perfusion of dihydro-beta erythroidine. These findings therefore provide anatomical and functional evidence for nAChR-mediated modulation of thalamocortical input to the prefrontal cortex. Such a mechanism may be relevant to the cognitive effects of nicotine and nicotinic antagonists. PMID- 9987009 TI - Stimulus-function, wind-up and modulation by diffuse noxious inhibitory controls of responses of convergent neurons of the spinal trigeminal nucleus oralis. AB - Extracellular unitary recordings were made from 53 spinal trigeminal nucleus oralis (Sp5O) convergent neurons in halothane-anaesthetized rats. The neurons had an ipsilateral receptive field including mainly oral or perioral regions. They responded to percutaneous electrical stimulation with two peaks of activation. The first had a short latency (4.3 +/- 0.3 ms) and low threshold (0.35 +/- 0.04 mA), whereas the second had a longer latency (68.1 +/- 3.4 ms) and higher threshold (7.3 +/- 0.5 mA). Intracutaneous injection of capsaicin (0.1%) produced a strong and rapid reduction of the long-latency responses of Sp5O convergent neurons with little effect on the short-latency responses. In most cases (73%), the long-latency responses exhibited a wind-up phenomenon during repetitive (0.66 Hz) suprathreshold electrical stimulation. These results suggest that C-fibres mediate the long-latency response of Sp5O convergent neurons. Regarding the C fibre-evoked responses, a linear relationship between the intensity of the applied current and the magnitude of the response was found within the one to three times threshold range. The Sp5O convergent neurons also encoded the intensity of mechanical stimuli applied to the skin or mucosa in the 5-50 g ranges. The evoked activity of Sp5O convergent neurons could be suppressed by noxious heat applied to the tail (52 degrees C) and long-lasting poststimulus effects followed this. These findings show that convergent neurons in the Sp5O resemble those in the deep laminae of the spinal dorsal horn and spinal trigeminal nucleus caudalis, and further support that the Sp5O plays a part in the processing of nociceptive information from the orofacial region. PMID- 9987010 TI - GABAC receptor rho subunits are heterogeneously expressed in the human CNS and form homo- and heterooligomers with distinct physical properties. AB - In the central nervous system, receptors for gamma-aminobutyric acid (GABA) are responsible for inhibitory neurotransmission. Anatomical and electrophysiological studies indicate that GABAC receptors are composed of rho subunits. While the rho 1 subunit of various species forms homooligomeric receptors with GABAC-like properties, molecular cloning has identified additional rho subunits whose functional role is unclear. By RT-PCR, we demonstrated that rho 1 expression is primarily restricted to the retina, whereas the rho 2 subunit was present in all brain regions tested. Transfection of HEK-293 cells with rho 2 cDNA resulted in GABA-gated whole-cell currents that differed from those mediated by the rho 1 subunit in two respects: maximal amplitude (rho 1:rho 2 approximately 4:1) and inactivation time course (rho 1:rho 2 approximately 2:1). Cotransfection of rho 1 and rho 2 cDNA in a 1:1 ratio generated whole-cell currents with large amplitudes characteristic of rho 1 but more rapid inactivation typical for rho 2. This observation suggested formation of heterooligomeric GABAC receptors with distinct features. Therefore, we tested the assembly of rho 1 and rho 2 subunits by cotransfecting rho 2 cDNA together with a chimeric rho 1 beta 1 subunit, known to interfere with rho 1 assembly in a dominant-negative fashion. Reduction of rho 2 generated currents correlated with the ratio of chimeric to rho 2 cDNA. Secondly, we determined that the picrotoxinin sensitivity of cells transfected with various ratios of rho 1 and rho 2 cDNA differed from that expected of a pure mixture of homooligomeric receptors. The latter two observations support the idea that rho 1 and rho 2 subunits form heterooligomeric GABAC receptors in mammalian cells. Together, our results indicate that the presence of both rho subunits enables the formation of heterooligomeric receptors with physical properties distinct from homooligomers, thus increasing the diversity of GABAC receptors in the CNS. PMID- 9987011 TI - Glutamate receptor phenotypes in the auditory brainstem and mid-brain of the developing rat. AB - Glutamate receptors mediate most excitatory synaptic transmission in the adult vertebrate brain, but their activation in developing neurons also influences developmental processes. However, little is known about the developmental regulation of the subunits composing these receptors. Here we have studied age dependent changes in the expression of alpha-amino-3-hydroxy-5-methyl-4-isoxazole (AMPA) and N-methyl-D-aspartate (NMDA) receptor subunits in the cochlear nucleus complex (CN), the superior olivary complex (SOC), the nuclei of the lateral lemniscus, and the inferior colliculus of the developing rat. In the lateral superior olive, the medial nucleus of the trapezoid body, and the ventral nucleus of the lateral lemniscus, the distribution of AMPA receptor subunits changed drastically with age. While GluR1 and GluR2 subunits were highly expressed in the first 2 postnatal weeks, GluR4 staining was detectable only thereafter. GluR1 and GluR2 immunoreactivities rapidly decreased during the third postnatal week, with the GluR1 subunits disappearing from most neurons. In contrast, the adult pattern of the distribution of AMPA receptor subunits emerged gradually in most of the other auditory nuclei. Thus, progressive as well as regressive events characterized AMPA receptor development in some nuclei, while a monotonically maturation was seen in other regions. In contrast, the staining patterns of NMDA receptor subunits remained stable or only decreased during the same period. Although our data are not consistent with a generalized pattern of AMPA receptor development, the abundance of GluR1 subunits is a distinctive feature of early AMPA receptors. As similar AMPA receptors are present during plasticity periods throughout the brain, neurons undergoing synaptic and structural remodelling might have a particular need for these receptors. PMID- 9987012 TI - Enhanced synaptic transmission and reduced threshold for LTP induction in fyn transgenic mice. AB - To elucidate the physiological role of Fyn, we analysed the properties of synaptic transmission and synaptic plasticity in hippocampal slices of mice overexpressing either wild-type Fyn (w-Fyn) or its constitutively active mutant (m-Fyn). These fyn-transgenes were driven by the calcium/calmodulin-dependent protein kinase II alpha promoter which turned on in the forebrain neurons including hippocampal pyramidal cells and in late neural development. In the hippocampal slices expressing m-Fyn the paired-pulse facilitation was reduced and the basal synaptic transmission was enhanced. A weak theta-burst stimulation, which was subthreshold for the induction of long-term potentiation (LTP) in control slices, elicited LTP in CA1 region of the slices expressing m-Fyn. When a relatively strong stimulation was applied, the magnitude of LTP in m-Fyn slices was similar to that in control slices. By contrast, the basal synaptic transmission and the threshold for the induction of LTP were not altered in the slices overexpressing wild-type Fyn. To examine the effect of expression of m-Fyn on GABAergic inhibitory system, we applied bicuculline, a GABAA receptor blocker, to the hippocampal slices. The ability of bicuculline to enhance excitatory postsynaptic potentials was attenuated in slices expressing m-Fyn, suggesting that the overexpression of m-Fyn reduced the GABAergic inhibition. The enhancement of synaptic transmission and the reduction of GABAergic inhibition may contribute to the enhanced seizure susceptibility in the mice expressing m Fyn. Thus, these results suggest that regulation of Fyn tyrosine kinase activity is important for both synaptic transmission and plasticity. PMID- 9987013 TI - Protective effects of idebenone and alpha-tocopherol on beta-amyloid-(1-42) induced learning and memory deficits in rats: implication of oxidative stress in beta-amyloid-induced neurotoxicity in vivo. AB - Amyloid beta-peptide (A beta), the major constituent of the senile plaques in the brains of patients with Alzheimer's disease, is cytotoxic to neurons and has a central role in the pathogenesis of the disease. Previous studies have suggested that oxidative stress is involved in the mechanisms of A beta-induced neurotoxicity in vitro. In the present study, we examined whether oxidative stress contributes to learning and memory deficits caused by continuous intracerebroventricular infusion of A beta-(1-42). In the A beta-(1-42)-infused rats, spontaneous alternation behaviour in a Y-maze and spatial memory in a water maze task were significantly impaired, as compared with A beta-(40-1)-infused control rats. The retention of passive avoidance learning was also significantly impaired by treatment with A beta-(1-42). Potent antioxidants idebenone and alpha tocopherol prevented the behavioural deficits in Y-maze and water maze, but not passive avoidance, tasks in A beta-(1-42)-infused rats when they were repeatedly administered by mouth once a day from 3 days before the start of A beta infusion to the end of behavioural experiments. Lipid peroxide levels in the hippocampus and cerebral cortex of A beta-(1-42)-infused rats did not differ from those in control animals, and neither idebenone nor alpha-tocopherol affected the lipid peroxide levels. These results suggest that treatment with antioxidants such as idebenone and alpha-tocopherol prevents learning and memory deficits caused by A beta. PMID- 9987014 TI - Poly(ADP ribose) polymerase cleavage precedes neuronal death in the hippocampus and cerebellum following injury to the developing rat forebrain. AB - Transient unilateral forebrain hypoxia-ischaemia (HI) in 14-day-old rats produces infarction and delayed neuronal death in the frontal cortex. Cell death can also be observed in regions distant from the primary injury, a phenomenon known as diaschisis. While apoptosis is involved in selective neuronal death, its role in infarction and diaschisis remains poorly understood. Here, we have investigated the proteolytic cleavage of poly(ADP ribose) polymerase (PARP) and the occurrence of apoptosis in the hippocampus and the cerebellum following either HI or traumatic brain injury. We demonstrate that: (i) in vitro, PARP is cleaved during apoptosis but not necrosis in cultured neuronal (N1E) cells and Swiss 3T3 fibroblasts; (ii) following HI, apoptotic cells can be detected by 4 h after injury in the hippocampus; (iii) in the ipsilateral hippocampus the appearance of cells with apoptotic morphology is preceded by a dramatic increase in PARP cleavage in the same region, starting immediately following HI and persisting for 24 h; (iv) HI also induces apoptosis in the cerebellum and, as in the hippocampus, the appearance of cells with apoptotic morphology is preceded by PARP cleavage that is greater on the side ipsilateral to forebrain injury; and (v) similarly, traumatic brain injury to the forebrain leads to PARP cleavage and apoptosis in the cerebellum. We conclude that HI injury or traumatic injury to the developing rat forebrain leads to PARP cleavage in directly affected areas and in sites distant from the primary injury that precedes the appearance of cells with apoptotic morphology. Our results are consistent with a role for apoptotic cell death in infarction and in diaschisis resulting from forebrain injury to the developing brain. PMID- 9987015 TI - Protein kinase C modulates field-evoked transmitter release from cultured rat cerebellar granule cells via a dendrotoxin-sensitive K+ channel. AB - The role of protein kinase C (PKC) in the control of neurotransmitter release from cultured rat cerebellar granule cells was investigated. Release of preloaded [3H]-D-aspartate which is incorporated into synaptic vesicles in this preparation was evoked by electrical field stimulation or elevated KCl. PKC activation by phorbol esters resulted in a large facilitation of field-evoked Ca(2+)-dependent [3H]-D-aspartate release and a lesser enhancement of KCl-stimulated release. Inhibition of PKC by Ro 31-8220 or staurosporine virtually abolished field-evoked release but had no effect on KCl-evoked release. Field-evoked, but not KCl evoked, synaptic vesicle exocytosis monitored by the fluorescent vesicle probe FM2-10 was inhibited by staurosporine. PKC was not directly modulating neurite Ca2+ channels coupled to release, as Ro 31-8220 did not inhibit these channels. Activation or inhibition of PKC modulated field-evoked plasma membrane depolarization, but had no effect on KCl-evoked depolarization, consistent with a regulation of Na+ or K+ channels activated by field stimulation. No modulation of field-evoked neurite Na+ influx was seen using phorbol esters. Phorbol ester induced facilitation of field-evoked [3H]-D-aspartate release and neurite Ca2+ entry was non-additive with that produced by the specific K+ channel antagonist dendrotoxin-1, suggesting that PKC modulates transmitter release from field stimulated cerebellar granule cells by inhibiting a dendrotoxin-1-sensitive K+ channel. PMID- 9987016 TI - The medullary dorsal reticular nucleus facilitates pain behaviour induced by formalin in the rat. AB - The influence of the dorsal reticular nucleus (DRt) on pain behaviour during the formalin test was studied in the rat by lesioning the nucleus through local application of electrical current or quinolinic acid. Animals in which the DRt was lesioned ipsilaterally to the paw injected with formalin spent less time in focused (licking, biting or scratching the injected paw) and total (focused pain behaviour plus protection of the injected paw during movements) pain behaviour, and showed paw-jerks less frequently than non-lesioned animals in both phases 1 and 2 of the test. Animals in which the DRt was lesioned contralaterally to the injected paw presented a decrease in total pain behaviour and number of paw-jerks only during phase 2. The number of superficial (laminae I-II) and deep (laminae III-VI) spinal dorsal horn cells expressing the c-fos proto-oncogene 2 h after subcutaneous injection of formalin was reduced by 34% and 50%, respectively, in animals with an ipsilateral DRt lesion as compared to non-lesioned rats. No differences in c-fos expression were observed after lesioning the DRt contralateral to the formalin injection. The results indicate that the DRt is involved in the facilitation of nociception during the formalin test by enhancing the response capacity of dorsal horn neurons to noxious stimulation. It is suggested that the pronociceptive action of the DRt is mediated by the reciprocal connections it establishes with the spinal dorsal horn. PMID- 9987017 TI - The effects of NMDA-induced retrohippocampal lesions on performance of four spatial memory tasks known to be sensitive to hippocampal damage in the rat. AB - Four separate cohorts of rats were employed to examine the effects of cytotoxic retrohippocampal lesions in four spatial memory tasks which are known to be sensitive to direct hippocampal damage and/or fornix-fimbria lesions in the rat. Selective retrohippocampal lesions were made by means of multiple intracerebral infusions of NMDA centred on the entorhinal cortex bilaterally. Cell damage typically extended from the lateral entorhinal area to the distal ventral subiculum. Experiment 1 demonstrated that retrohippocampal lesions spared the acquisition of a reference memory task in the Morris water maze, in which the animals learned to escape from the water by swimming to a submerged platform in a fixed location. In the subsequent transfer test, when the escape platform was removed, rats with retrohippocampal lesions tended to spend less time searching in the appropriate quadrant compared to controls. Experiment 2 demonstrated that the lesions also spared the acquisition of a working memory version of the water maze task in which the location of the escape platform was varied between days. In experiment 3, both reference and working memory were assessed using an eight arm radial maze in which the same four arms were constantly baited between trials. In the initial acquisition, reference memory but not working memory was affected by the lesions. During subsequent reversal learning in which previously baited arms were now no longer baited and vice versa, lesioned animals made significantly more reference memory errors as well as working memory errors. In experiment 4, spatial working memory was assessed in a delayed matching-to position task conducted in a two-lever operant chamber. There was no evidence for any impairment in rats with retrohippocampal lesions in this task. The present study demonstrated that unlike direct hippocampal damage, retrohippocampal cell loss did not lead to a general impairment in spatial learning, implying that the integrity of the retrohippocampus and/or its interconnection with the hippocampal formation is not critical for normal hippocampal-dependent spatial learning and memory. This outcome is surprising for a number of current hippocampal theories, and suggests that other cortical as well as subcortical inputs to the hippocampus might be of more importance, and further raises the question regarding the functional significance of the retrohippocampal region. PMID- 9987018 TI - CaMKII-dependent phosphorylation of NR2A and NR2B is decreased in animals characterized by hippocampal damage and impaired LTP. AB - The calcium-calmodulin-dependent protein kinase II (CaMKII) subserves activity dependent plasticity in central neurons. To examine in vivo the implication of CaMKII activity in synaptic plasticity, we used an animal model characterized by developmentally induced targeted neuronal ablation within the cortex and the hippocampus, and showing, at presynaptic level, molecular alterations leading to facilitation of glutamate release in hippocampal synapses (methylazoxymethanol treated rats, MAM-rats). We report here that at the postsynaptic side, the activity of CaMKII is markedly decreased in MAM-rats when compared to controls, although the concentration of the enzyme in Post Synaptic Density (PSD) is not altered. This effect is confined to PSD-associated CaMKII, as enzyme activity tested in the soluble fraction is unchanged in MAM-rats. In addition, the decreased activity is not due to inhibition by autophosphorylation in specific sites within the calmodulin-binding domain, as preincubation with purified phosphatases 1 and 2A failed to restore CaMKII activity in PSD of MAM-rats. The CaMKII-dependent phosphorylation of NR2A/B subunits of NMDA receptor is lower in MAM-rats when compared to controls (51.77 +/- 7.39% of controls level), as revealed in back-phosphorylation experiments. In addition, a treatment able to restore long-term potentiation (LTP) in hippocampal slices from MAM-rats, e.g. exposure to D-serine, is able to restore CaMKII activity to the control value. PMID- 9987020 TI - Characteristics of slow and fast phases of the optocollic reflex (OCR) in head free pigeons (Columba livia): influence of flight behaviour. AB - The effect of behavioural context on the properties of slow and fast phases of the horizontal optocollic reflex (OCR) were investigated in head free pigeons for two situations, i.e.: (i) animals were hung in a harness ('resting condition'); (ii) animals were additionally submitted to a frontal airflow that provoked a flight posture ('flying condition') [Bilo and Bilo (1983) J. Comp. Physiol., 153, 111]. A 'transient flight' was also provoked in the 'resting condition' by tapping the breastbone region. Stimuli consisted either of velocity steps (30-300 degrees/s) or of an increasing velocity stimulus (0-300 degrees/s). The amplitude of nystagmic beats and the OCR gain increased in the 'flying condition' and during 'transient flight' as compared to the 'resting condition'. The OCR working range was considerably extended toward high velocities by the flying behaviour. In the 'resting condition', spontaneous head oscillations generally triggered a high-gain OCR, close to that obtained in the 'flying condition'. One-third of the animals showed a higher gain in response to an increasing velocity stimulus than with step stimuli, in the high velocity range. The linear relation between amplitude and peak velocity of OCR fast phases was independent of the stimulation velocity in the 'resting condition', whereas the amplitude and peak velocity increased with the stimulation velocity in the 'flying condition'. In this condition, the fast phase velocity was correlated with the slow phase velocity, but not with the retinal slip velocity. Thus, both the slow and fast phases of the OCR are dependent on the behavioural context. PMID- 9987019 TI - Characterization of cultured dorsal root ganglion neuron P2X receptors. AB - P2X receptors for adenosine 5'-triphosphate (ATP) comprise a family of ligand gated cation channels with distinct characteristics which are dependent on the receptor subunits (P2X1-7) expressed, and the homomeric or heteromeric assembly of protein subunits in individual cells. We describe the properties of P2X receptors expressed by cultured adult rat dorsal root ganglion cells on the basis of the time course of responses to ATP, alpha, beta-methylene adenosine 5' triphosphate (alpha, beta-meATP) and 2-methyl-thioadenosine 5'-triphosphate (2 meSATP), and using the antagonists 2',3'-O-(2,4,6-trinitrophenyl) ATP (TNP-ATP), a novel and highly selective purinoceptor antagonist, suramin and iso pyridocalphosphate-6-azophenyl-2',5' disulphonic acid (PPADS). ATP (10 microM) evoked inward currents in approximately 95% of neurons tested and > 80% responded with a fast transient inward current that rapidly inactivated during the continued presence of ATP. Of the remaining neurons, approximately 4% showed a sustained response and approximately 10% showed a combination of transient and sustained components. Rapid application of ATP, alpha,beta-meATP and 2meSATP demonstrated these to be full agonists of the rapidly inactivating P2X receptor (pA50 values = 5.83, 5.86 and 5.55, respectively), whilst uridine triphosphate (UTP) and 1-beta,gamma-methyleneadenosine 5'-triphosphate (1-beta,gamma-meATP) were ineffective as agonists. These rapidly inactivating responses could be inhibited by TNP-ATP, suramin and PPADS (pIC50 = 9.5, 6.5, 6.4, respectively). Using inactivation protocols, we demonstrate the presence of homomeric P2X3-like receptors and non-inactivating P2X receptors, which indicates that individual subsets of adult dorsal root ganglion neurons have distinct P2X receptor phenotypes, and that individual DRG neurons may express multiple P2X receptor subtypes. PMID- 9987021 TI - Chloride-dependent transport of NH4+ into bee retinal glial cells. AB - Mammalian astrocytes convert glutamate to glutamine and bee retinal glial cells convert pyruvate to alanine. To maintain such amination reactions these glial cells may take up NH4+/NH3. We have studied the entry of NH4+/NH3 into bundles of glial cells isolated from bee retina by using the fluorescent dye BCECF to measure pH. Ammonium caused intracellular pH to decrease by a saturable process: the rate of change of pH was maximal for an ammonium concentration of about 5 mM. This acidifying response to ammonium was abolished by the loop diuretic bumetanide (100 microM) and by removal of extracellular Cl-. These results strongly suggest that ammonium enters the cell by contransport of NH4+ with Cl-. Removal of extracellular Na+ did not abolish the NH(4+)-induced acidification. The NH(4+)-induced pH change was unaffected when nearly all K+ conductance was blocked with 5 mM Ba2+ showing that NH4+ did not enter through Ba(2+)-sensitive ion channels. Application of 2 mM NH4+ led to a large increase in total intracellular proton concentration estimated to exceed 13.5 mEq/L. As the cell membrane appeared to be permeable to NH3, we suggest that when NH4+ entered the cells, NH3 left, so that protons were shuttled into the cell. This shuttle, which was strongly dependent on internal and external pH, was quantitatively modelled. In retinal slices, 2 mM NH4+ alkalinized the extracellular space: this alkalinization was reduced in the absence of bath Cl-. We conclude that NH4+ enters the glial cells in bee retina on a cotransporter with functional similarities to the NH4+(K+)-Cl- cotransporter described in kidney cells. PMID- 9987022 TI - Impaired glucocorticoid receptor function evolves in aberrant physiological responses to bacterial endotoxin. AB - The consequences of glucocorticoid receptor (GR) dysfunction for neuroimmunoendocrine responses to an inflammatory challenge were studied in transgenic mice expressing antisense RNA directed against the GR [GR-impaired (GR i) mice]. Mice were implanted intraperitoneally with a biotelemetry transmitter to monitor body temperature and locomotion. GR-i mice showed decreased locomotion and body temperature during the dark phase of the diurnal cycle. Intraperitoneal administration of saline caused a rapid increase in body temperature in control mice, which was terminated within 90 min. In GR-i mice, however, body temperature remained elevated for about 6 h. Intraperitoneal injection of endotoxin (10 micrograms/mouse) produced a biphasic fever in control mice. However, in endotoxin-injected GR-i mice, body temperature was not significantly different from their saline-injected controls during the first 6 h. Body temperature then increased and remained elevated during the night period. Both strains showed hypolocomotion after endotoxin. In a second experiment, mice were injected intraperitoneally with saline or endotoxin and killed after 1, 3, 6 or 24 h. In GR-i mice, endotoxin caused an augmented rise in plasma ACTH, but not in corticosterone levels. The endotoxin-induced increase in serum levels of interleukin-1 beta and interleukin-6 was not different between the strains. However, whereas in control mice tumour necrosis factor-alpha levels were below detection at the time points studied, substantial levels of this cytokine were found in the serum of GR-i mice 1 h after endotoxin administration. It may be concluded that life-long impairment of GR evolves in aberrant physiological and humoral responses to an acute inflammatory challenge. These findings expand our understanding about the neuroendocrine and physiological disturbances associated with stress-related disorders. PMID- 9987023 TI - Differential projection patterns of superior and inferior collicular neurons onto posterior paralaminar nuclei of the thalamus surrounding the medial geniculate body in the rat. AB - The thalamic nuclei at the medial border of the medial geniculate body (i.e. the suprageniculate nucleus, the medial division of the medial geniculate nucleus, the posterior intralaminar nucleus and the peripeduncular nucleus) which relay sensory information to the amygdala are thought to receive convergent input from multiple sites. In order to delineate the organization of these multimodal thalamic nuclei, the locations of superior and inferior collicular neurons projecting to these nuclei were studied by means of retrograde transport methods. Small injections of the tracer Miniruby were made into single paralaminar thalamic nuclei. Injections of Miniruby into the suprageniculate nucleus labelled predominantly neurons in the stratum opticum of the superior colliculus, whereas injections into the medial division of the medial geniculate body, the posterior intralaminar nucleus and the peripeduncular nucleus labelled predominantly neurons in the deep layers of the superior colliculus. These injections also labelled neurons in the inferior colliculus. The majority of retrogradely labelled neurons were found in the external nucleus of the inferior colliculus and here predominantly in layer 2. Injections focused onto the medial division of the medial geniculate body additionally labelled magnocellular neurons in layer 3 of the external nucleus and a few neurons in the central nucleus. More ventrally located injections, focused onto the posterior intralaminar and peripeduncular nucleus, almost exclusively labelled neurons in layer 1 of the external nucleus and the dorsal part of the dorsal nucleus. After injections into the suprageniculate nucleus, only neurons in layer 2 were found. Neurons in the central nucleus of the inferior colliculus were only found after injections that involved the medial division of the medial geniculate body. The present results suggest that, despite a considerable degree of convergence in this thalamic region, each of these thalamic nuclei receives a unique pattern of projections from the superior and inferior colliculi. It appears that the thalamic nuclei may be concerned mainly, but not exclusively, with a single sensory modality, and give rise to parallel multimodal and unimodal pathways to the amygdala. PMID- 9987025 TI - Pontine and medullary control of the respiratory activity in the trigeminal and facial nerves of the newborn mouse: an in vitro study. AB - In vitro, the respiratory activity in rodents is characterized by: (i) the rapidly peaking, slowly decrementing pattern of spontaneous and rhythmic active phases recorded from the motor rootlets, and (ii) the specific location of their rhythmic generator in the ventrolateral medulla. The aim of the present study was to assess whether the trigeminal and facial motor rootlets still exhibit respiratory activity in the absence of peripheral and higher cerebral structures, and to compare the onset of their active phases with that of other respiratory rootlets, using the in vitro isolated brainstem--spinal cord preparation of the newborn mouse and rat. Spontaneous rhythmic activity was recorded from the trigeminal and facial rootlets. It was regular and synchronized bilaterally and ipsilaterally with the hypoglossal or cervical C1-C6 rootlets. Brainstem transection experiments demonstrated that for both the trigeminal and facial rootlets, the spontaneous rhythmic activity originates from the medulla, in a region consistent with the pre-Botzinger complex and the rostral ventrolateral medulla. The pattern of the respiratory motor activity recorded from the trigeminal and facial rootlets was identical to the pattern recorded from the hypoglossal and cervical C1-C6 rootlets with rapidly peaking, slowly decrementing characteristics. The duration of the ascending part and the total duration of their active phases were similar. The onset of the active phases of the phrenic rootlets was delayed compared with that of the trigeminal, facial and hypoglossal rootlets. However, no difference in the onsets of the active phases of the cranial rootlets could be observed. Removal of the rostral pons suppressed the delay in onset of the active phases of the phrenic rootlets. Our findings show that: (i) rhythmic activities of the trigeminal and facial rootlets are preserved in absence of control by peripheral or high cerebral structures; (ii) the pattern and the location of the rhythmic generator for these activities are of the respiratory type; and (iii) the rostral pons is responsible for a delay in the onset of the active phases of the phrenic rootlets compared with that of the trigeminal, facial and hypoglossal rootlets. PMID- 9987024 TI - TrkA activation in the rat visual cortex by antirat trkA IgG prevents the effect of monocular deprivation. AB - It has been recently shown that intraventricular injections of nerve growth factor (NGF) prevent the effects of monocular deprivation in the rat. We have tested the localization and the molecular nature of the NGF receptor(s) responsible for this effect by activating cortical trkA receptors in monocularly deprived rats by cortical infusion of a specific agonist of NGF on trkA, the bivalent antirat trkA IgG (RTA-IgG). TrkA protein was detected by immunoblot in the rat visual cortex during the critical period. Rats were monocularly deprived for 1 week (P21-28) and RTA-IgG or control rabbit IgG were delivered by osmotic minipumps. The effects of monocular deprivation on the ocular dominance of visual cortical neurons were assessed by extracellular single cell recordings. We found that the shift towards the ipsilateral, non-deprived eye was largely prevented by RTA-IgG. Infusion of RTA-IgG combined with antibody that blocks p75NTR (REX), slightly reduced RTA-IgG effectiveness in preventing monocular deprivation effects. These results suggest that NGF action in visual cortical plasticity is mediated by cortical TrkA receptors with p75NTR exerting a facilitatory role. PMID- 9987026 TI - Local inhibition of hippocampal nitric oxide synthase does not impair place learning in the Morris water escape task in rats. AB - Recent studies have provided evidence that nitric oxide (NO) has a role in certain forms of memory formation. Spatial learning is one of the cognitive abilities that has been found to be impaired after systemic administration of an NO-synthase inhibitor. As the hippocampus has a pivotal role in spatial orientation, the present study examined the role of hippocampal NO in spatial learning and reversal learning in a Morris task in adult rats. It was found that N omega-nitro-L-arginine infusions into the dorsal hippocampus affected the manner in which the rats were searching the submerged platform during training, but did not affect the efficiency to find the spatial location of the escape platform. Hippocampal NO-synthase inhibition did not affect the learning of a new platform position in the same water tank (i.e. reversal learning). Moreover, no treatment effects were observed in the probe trials (i.e. after acquisition and after reversal learning), indicating that the rats treated with N omega-nitro-L arginine had learned the spatial location of the platform. These findings were obtained under conditions where the NO synthesis in the dorsal hippocampus was completely inhibited. On the basis of the present data it was concluded that hippocampal NO is not critically involved in place learning in rats. PMID- 9987027 TI - Cerebellar granule-cell-specific GABAA receptors attenuate benzodiazepine-induced ataxia: evidence from alpha 6-subunit-deficient mice. AB - Benzodiazepine- and alcohol-induced ataxias in rodents have been proposed to be affected by the gamma-aminobutyric acid type A (GABAA) receptor alpha 6 subunit, which contributes to receptors specifically expressed in cerebellar granule cells. We have studied an alpha 6 -/- mouse line for motor performance and drug sensitivity. These mice, as a result of a specific genetic lesion, carry a precise impairment at their Golgi-granule cell synapses. On motor performance tests (rotarod, horizontal wire, pole descending, staircase and swimming tests) there were no robust baseline differences in motor function or motor learning between alpha 6 -/- and alpha 6 +/+ mice. On the rotarod test, however, the mutant mice were significantly more impaired by diazepam (5-20 mg/kg, i.p.), when compared with alpha 6 +/+ control and background C57BL/6J and 129/SvJ mouse lines. Ethanol (2.0-2.5 g/kg, i.p.) produced similar impairment in the alpha 6 -/ and alpha +/+ mice. Diazepam-induced ataxia in alpha 6 -/- mice could be reversed by the benzodiazepine site antagonist flumazenil, indicating the involvement of the remaining alpha 1 beta 2/3 gamma 2 GABAA receptors of the granule cells. The level of activity in this synapse is crucial in regulating the execution of motor tasks. We conclude that GABAA receptor alpha 6 subunit dependent actions in the cerebellar cortex can be compensated by other receptor subtypes; but if not for the alpha 6 subunit, patients on benzodiazepine medication would suffer considerably from ataxic side-effects. PMID- 9987028 TI - Intrastriatal grafting of a GDNF-producing cell line protects striatonigral neurons from quinolinic acid excitotoxicity in vivo. AB - Glial cell line-derived neurotrophic factor (GDNF) is a neurotrophic factor with a therapeutic potential in neurodegenerative disorders. GDNF is expressed in the adult striatum, but its signalling tyrosine kinase receptor, c-ret, has not been detected in this structure by in situ hybridization. In the present work, we first examined c-ret and GDNF receptor alpha 1 (GFR-alpha 1) expression using an RNAse protection assay, and found that both receptors are expressed in the adult rat striatum. We then examined whether GDNF was able to regulate the phenotype and/or prevent the degeneration of striatal projection neurons in a well characterized model of excitotoxic damage. A fibroblast cell line, engineered to overexpress GDNF, was grafted in adult rats striatum 24 h before quinolinic acid (QUIN) injection. QUIN injection alone or in combination with the control cell line induced a loss of glutamic acid decarboxylase 67 (GAD)-, preprotachykinin A (PPTA)-, prodynorphin (DYN)- and preproenkephalin (PPE)-positive neurons. GDNF selectively prevented: (i) the loss of a subpopulation of striatonigral neurons expressing GAD and PPTA; (ii) the atrophy of PPTA-positive neurons; and (iii) the decrease in GAD, PPTA and DYN mRNA expression, after QUIN injection. Moreover, in unlesioned animals, GDNF increased the size of PPTA-positive neurons and up regulated their mRNA levels. In contrast, GDNF showed no effect in intact or lesioned striatopallidal PPE-positive neurons. Thus, our findings show that GDNF selectively regulates the phenotype and protects striatonigral neurons from QUIN induced excitotoxicity, suggesting that GDNF may be used for the treatment of striatonigral degenerative disorders, e.g. Huntington's disease and multiple system atrophy. PMID- 9987029 TI - A new pyrrolyl-quinoxalinedione series of non-NMDA glutamate receptor antagonists: pharmacological characterization and comparison with NBQX and valproate in the kindling model of epilepsy. AB - Antagonists at the ionotropic non-NMDA [AMPA (amino-methyl proprionic acid)/kainate] type of glutamate receptors have been suggested to possess several advantages compared to NMDA (N-methyl-D-aspartate) receptor antagonists, particularly in terms of risk/benefit ratio, but the non-NMDA receptor antagonists available so far have not fulfilled this promise. From a large series of pyrrolyl-quinoxalinedione derivatives, we selected six new competitive non NMDA receptor antagonists. The basis of selection was high potency and selectivity for AMPA and/or kainate receptors, high in vivo potency after systemic administration, and an acceptable ratio between neuroprotective or anticonvulsant effects and adverse effects. Pharmacological characteristics of these novel compounds are described in this study with special emphasis on their effects in the kindling model of temporal lobe epilepsy, the most common type of epilepsy in humans. In most experiments, NBQX and the major antiepileptic drug valproate were used for comparison with the novel compounds. The novel non-NMDA receptor antagonists markedly differed in their AMPA and kainate receptor affinities from NBQX. Thus, while NBQX essentially did not bind to kainate receptors at relevant concentrations, several of the novel compounds exhibited affinity to rat brain kainate receptors or recombinant kainate receptor subtypes in addition to AMPA receptors. One compound, LU 97175, bound to native high affinity kainate receptors and rat GluR5-GluR7 subunits, i.e. low affinity kainate binding sites, with much higher affinities than to AMPA receptors. All compounds potently blocked AMPA-induced cell death in vitro and, except LU 97175, AMPA-induced convulsions in vivo. In the kindling model, compounds with a high affinity for GluR7 (LU 97175) or compounds (LU 115455, LU 136541) which potently bind to AMPA receptors and low affinity kainate receptor subunits were potent anticonvulsants in the kindling model, whereas the AMPA receptor-selective LU 112313 was the least selective compound in this model, indicating that non-NMDA antagonists acting at both AMPA and kainate receptors are more effective in this model than AMPA receptor-selective drugs. Three of the novel compounds, i.e. LU 97175, LU 115455 and LU 136541, exerted potent anticonvulsant effects without inducing motor impairment in the rotarod test. This combination of actions is thought to be a prerequisite for selective anticonvulsant drug action. PMID- 9987030 TI - Increased cyclin D1 in vulnerable neurons in the hippocampus after ischaemia and epilepsy: a modulator of in vivo programmed cell death? AB - Several observations suggest that delayed neuronal death in ischaemia, epilepsy and other brain disorders includes an apoptotic component, involving programmed cell death (PCD). PCD is hypothesized to result, in part, from aberrant control of the cell cycle. Because they are instrumental in mitosis, cyclins D are key markers to evaluate whether neurons indeed progress into the cell cycle in situations of pathology. Therefore, we investigated in rat brains, the expression of cyclins D in the delayed neuronal death that occurs following transient global ischaemia and kainate-induced seizures. Following a four-vessel occlusion insult, quantitative in situ hybridization revealed a highly significant and persistent 100% increase of cyclin D1 mRNA in the vulnerable pyramidal neurons of the CA1 hippocampal region. Ischaemia also induced a smaller and transient cyclin D1 mRNA increase in the resistant CA3 area and dentate gyrus. In contrast, the cyclin D2 and D3 mRNAs, expressed constitutively in the adult rat hippocampus, were not upregulated. Following kainate-induced seizures, cyclin D1 mRNA was induced in the vulnerable CA3 region, and to a lesser extent, in non-vulnerable regions. Cyclin D1 immunohistochemistry revealed increased protein levels in the cytoplasm and nucleus of neurons commited to die after ischaemia. Double labelling experiments indicate that cyclin D1 is also expressed in reactive astrocytes but not in microglial cells. Finally, we report that in neurons, cyclin D1 expression peaks before nuclear condensation and the appearance of DNA fragmentation. We propose that cyclin D1, when expressed at high levels in lesioned neurons, may act as a modulator of apoptosis. PMID- 9987031 TI - Modulation of neurotransmitter release by dihydropyridine-sensitive calcium channels involves tyrosine phosphorylation. AB - Cultured rat cerebellar granule cells depolarized by high KCl, display a large component of Ca2+ influx through L-type voltage-dependent Ca2+ channels as defined by a sensitivity to 1 microM nifedipine. This Ca2+ influx is not coupled to neurotransmitter exocytosis but has implications for neuronal development. KCl stimulation in the absence of external Ca2+ followed by the readdition of Ca2+ allows the coupling of a class of L-type Ca2+ channels to neurotransmitter exocytosis as assessed by loading of glutamatergic pools with [3H]-D-aspartate. KCl stimulation in the absence of external Ca2+ ('predepolarization') enhances tyrosine phosphorylation of several cellular proteins, and inhibitors of tyrosine kinases block both phosphorylation and the neurotransmitter release coupled to the L-type Ca2+ channel. More specifically, an inhibitor of src family tyrosine kinases, PP1, blocks the effects of predepolarization suggesting a role for a src family kinase in the process. Furthermore, L-type Ca2+ channel recruitment and modulation of release could be activated with the tyrosine phosphatase inhibitor sodium orthovanadate. The phosphoproteins enhanced by predepolarization, which include the cytoskeletal proteins focal adhesion kinase (FAK) and vinculin, are also highly phosphorylated early on in culture when neurite outgrowth occurs. As the neurons develop a network of neurites, both tyrosine phosphorylation and L type Ca2+ channel activity decrease. These results show a novel mechanism for the recruitment of L-type Ca2+ channels and their coupling to neurotransmitter release which involves tyrosine phosphorylation. This phenomenon has a role in cerebellar granule cell development. PMID- 9987032 TI - Subcellular distribution of survival motor neuron (SMN) protein: possible involvement in nucleocytoplasmic and dendritic transport. AB - Spinal muscular atrophy (SMA) is among the most common recessive autosomal diseases and is characterized by the loss of spinal motor neurons. A gene termed 'Survival of Motor Neurons' (SMN) has been identified as the SMA-determining gene. Recent work indicates the involvement of the SMN protein and its associated protein SIP1 in spliceosomal snRNP biogenesis. However, the function of SMN remains unknown. Here, we have studied the subcellular localization of SMN in the rat spinal cord and more generally in the central nervous system (CNS), by light fluorescence and electron microscopy. SMN immunoreactivity (IR) was found in the different regions of the spinal cord but also in various regions of the CNS such as the brainstem, cerebellum, thalamus, cortex and hippocampus. In most neurons, we observed a speckled labelling of the cytoplasm and a discontinuous staining of the nuclear envelope. For some neurons (e.g. brainstem nuclei, dentate gyrus, cortex: layer V) and, in particular in motoneurons, SMN-IR was also present as prominent nuclear dot-like-structures. In these nuclear dots, SMN colocalized with SIP1 and with fibrillarin, a marker of coiled bodies. Ultrastructural studies in the anterior horn of the spinal cord confirmed the presence of SMN in the coiled bodies and also revealed the protein at the external side of nuclear pores complexes, in association with polyribosomes, and in dendrites, associated with microtubules. These localizations suggest that, in addition to its involvement in the spliceosome biogenesis, the SMN protein could also play a part in nucleocytoplasmic and dendritic transport. PMID- 9987033 TI - Different cortical organization of visceral and somatic sensation in humans. AB - Sensory stimuli from the visceral domain exhibit perceptual characteristics different from stimuli applied to the body surface. Compared with somatosensation there is not much known about the cortical projection and functional organization of visceral sensation in humans. In this study, we determined the cortical areas activated by non-painful electrical stimulation of visceral afferents in the distal oesophagus, and somatosensory afferents in the median nerve and the lip in seven healthy volunteers using whole-head magnetoencephalography. Stimulation of somatosensory afferents elicited short-latency responses (approximately 20-60 ms) in the primary somatosensory cortex (SI) contralateral (median nerve) or bilateral (lip) to the stimulated side, and long-latency responses (approximately 60-160 ms) bilaterally in the second somatosensory cortex (SII). In contrast, stimulation of visceral oesophageal afferents did not evoke discernible responses in SI but well reproducible bilateral SII responses (approximately 70-190 ms) in close vicinity to long-latency SII responses following median nerve and lip stimuli. Psychophysically, temporal discrimination of successive stimuli became worse with increasing stimulus repetition rates (0.25 Hz, 0.5 Hz, 1 Hz, 2 Hz) only for visceral oesophageal, but not for somatosensory median nerve stimuli. Correspondingly, amplitudes of the first cortical response to oesophageal stimulation emerging in the SII cortex declined with increasing stimulus repetition rates whereas the earliest cortical response elicited by median nerve stimuli (20 ms SI response) remained unaffected by the stimulus frequency. Our results indicate that visceral afferents from the oesophagus primarily project to the SII cortex and, unlike somatosensory afferents, lack a significant SI representation. We propose that this cortical projection pattern forms the neurophysiological basis of the low temporal and spatial resolution of conscious visceral sensation. PMID- 9987034 TI - Myelin does not influence the choice behaviour of entorhinal axons but strongly inhibits their outgrowth length in vitro. AB - Myelin is crucial for the stabilization of the entorhinohippocampal projection during late development and is a non-permissive substrate for regrowing axons after lesion in the adult brain. We used two in vitro assays to analyse the impact of myelin on rat entorhinohippocampal projection neurons. A stripe assay was used to study the impact of myelin on the choice behaviour of axons from the entorhinal cortex (EC). Given a choice between alternating hippocampal membrane lanes from developmental stages ranging from early postnatal to adult, EC axons preferred to extend on early postnatal hippocampal membranes. Neither the neutralization of myelin-associated factors by a specific antibody (IN-1) nor the separation of myelin from membranes interfered with the axons' choice behaviour. The entorhinal axons showed no preference in the membrane combination of adult and myelin-free adult hippocampal membranes. These stripe assay experiments demonstrate that support for EC axon choice in the developing hippocampus is maturation-dependent and is not influenced by myelin. The application of IN-1 in the outgrowth assay and the separation of myelin from membranes, enhanced elongation of outgrowing entorhinal axons on adult hippocampal membranes, whereas a control antibody did not. This shows that myelin-associated factors have a strong inhibitory effect on the outgrowth length of entorhinal axons. In conclusion, we suggest that axonal elongation in the entorhinohippocampal system during development is strongly influenced by myelin-associated growth inhibition factors and that specific target finding of entorhinal axons is regulated by a different mechanism. PMID- 9987035 TI - Zn2+ entry produces oxidative neuronal necrosis in cortical cell cultures. AB - Evidence has accumulated that Zn2+ plays a central role in neurodegenerative processes following brain injuries including ischaemia or epilepsy. In the present study, we examined patterns and possible mechanisms of Zn2+ neurotoxicity. Inclusion of 30-300 microM Zn2+ for 30 min caused neuronal necrosis apparent by cell body and mitochondrial swelling in cortical cell cultures. This Zn2+ neurotoxicity was not attenuated by antiapoptosis agents, inhibitors of protein synthesis or caspase. Blockade of glutamate receptors or nitric oxide synthase showed no beneficial effect against Zn2+ neurotoxicity. Interestingly, antioxidants, trolox or SKF38393, attenuated Zn(2+)-induced neuronal necrosis. Pretreatment with insulin or brain-derived neurotrophic factor increased the Zn(2+)-induced free radical injury. Kainate or AMPA facilitated Zn2+ entry and potentiated Zn2+ neurotoxicity in a way sensitive to trolox. Reactive oxygen species and lipid peroxidation were generated in the early phase of Zn2+ neurotoxicity. These findings indicate that entry and accumulation of Zn2+ result in generation of toxic free radicals and then cause necrotic neuronal degeneration under certain pathological conditions in the brain. PMID- 9987036 TI - Nitric oxide is required for expression of LTP that is induced by stimulation phase-locked with theta rhythm. AB - Long-term potentiation (LTP) can be induced by giving only one burst (five stimuli at 200 Hz) on the positive phase of sensory-induced theta rhythm in awake or anaesthetized rats, a stimulation protocol that mimics naturally occurring neuronal activity. Nitric oxide has been discussed as an important neuronal messenger in the induction of LTP. However, experiments testing inhibitors of nitric oxide synthase (NOS) in vitro produced contradictory results. The non specific NOS inhibitor Nitro-L-arginine (L-NARG) impaired LTP induced by high frequency stimulation (HFS) [from 155 +/- 7% to 122 +/- 8%), but completely blocked theta-dependent LTP induction (161 +/- 8% to 102 +/- 5%). NOS inhibitors, e.g. 7-nitro indazole (7-NI) or 1-(2-trifluoromethylphenyl) imidazole (TRIM) that are more selective for neuronal NOS and affect blood pressure less also impaired HFS-induced LTP (186 +/- 11% to 135 +/- 9% for TRIM) but completely blocked theta dependent LTP (154 +/- 7 to 91 +/- 8). L-Arginine reversed the effects of the NOS inhibitors tested. Therefore, NO appears to be a modulator that is important for synaptic plasticity in this more physiological stimulation technique in vivo. NO is not released in slice preparations in sufficient quantities or at the right timing. Instead, the unphysiologically strong HFS protocol appears to induce an NO-independent type of LTP in some cases. PMID- 9987037 TI - Sustained activation of hippocampal pyramidal cells by 'space clamping' in a running wheel. AB - In contrast to sensory cortical areas of the brain, the relevant physiological inputs to the hippocampus, leading to selective activation of pyramidal cells, are largely unknown. Pyramidal cells are thought to be phasically activated by spatial cues and a variety of sensory and motor stimuli. Here, we used a behavioural 'space clamp' method, which involved the confinement of the actively running animal in a defined position in space (running wheel) and kept sensory inputs constant. Twelve percent of the recorded CA1 pyramidal cells were selectively active while the rat was running in the wheel. Cell firing was specific to the direction of running and disappeared after rotating the recording apparatus. The discharge frequency of pyramidal cells and interneurons was sustained as long as the rat ran continuously in the wheel. Furthermore, the discharge frequency of pyramidal cells and interneurons increased with increasing running velocity, even though the frequency of hippocampal theta waves remained constant. The discharge frequency of some 'wheel-related' pyramidal cells could increase more than 10-fold between 10 and 100 cm/s, whereas the firing rate of 'non-wheel' cells remained constantly low. We hypothesize that: (i) a necessary condition for place-specific discharge of hippocampal pyramidal cells is the presence of theta oscillation; and (ii) relevant stimuli can tonically and selectively activate hippocampal pyramidal cells as long as theta activity is present. PMID- 9987038 TI - Rapid desensitization converts prolonged glutamate release into a transient EPSC at ribbon synapses between retinal bipolar and amacrine cells. AB - The mechanisms underlying the conversion of prolonged glutamate release from ribbon synapses in bipolar cells to sustained and transient excitatory postsynaptic responses in identified retinal amacrine cells were studied in tiger salamander (Ambystoma tigrinum) retina. A retina slice preparation with whole cell patch recording techniques under voltage- and current-clamp conditions was used to assay the electrical properties of bipolar and amacrine cells. Amacrine cells were categorized into two basic forms: (i) transient amacrine cells that respond to a step of light with a burst of spikes only at the transitions of the step; and (ii) sustained amacrine cells that respond with continuous spiking during the entire light step. The two cell types each had a characteristic morphology: transient amacrine cells possessed wide dendritic fields (chi = 375 microns), while sustained cells had much more narrowly confined dendritic fields (chi = 85 microns). Whole cell voltage-gated currents of the transient and sustained cell types were not significantly different. Both cell types had spikes that were sensitive to tetradotoxin (TTX, 0.3 microM) with voltage deflections of up to 100 mV. Light-evoked excitatory synaptic currents relaxed rapidly in transient neurons (tau 1/2 = 100 ms) and more slowly in sustained neurons (tau 1/2 = 1.2 s). EPSCs in both cells reversed near 0 mV. Rapid application of glutamate or kainate elicited rapidly desensitizing ionic currents (tau 1/2 = 85 ms) followed by a slowly desensitizing component. Cyclothiazide, a drug that eliminates rapid desensitization, lengthened the time course of the glutamate gated current from tau 1/2 = 85 ms to about 3 s, and the relaxation kinetics of the glutamatergic EPSC from tau 1/2 = 85 ms to about 1.0 s. These data suggest that a key determinant in forming transient versus sustained responses in amacrine cells of vertebrate retina is the differences in their excitatory, glutamatergic synaptic inputs, and that rapid desensitization of glutamate receptors plays a role in converting the presynaptic signal associated with sustained glutamate release into a postsynaptic, transient signal at the ribbon synapse. PMID- 9987039 TI - Effects of dorsolateral spinal lesions on stretch reflex threshold and stiffness in awake cats. AB - Measurements of threshold angle and incremental dynamic stiffness (IDS) were derived from triceps surae stretch reflexes, elicited by ramp and hold flexion at the ankle joint of four cats that were tested while awake. Stretch reflexes were assessed from trials that began from different ankle joint start positions or were matched using a post-hoc analysis for initial background force during testing sessions before and following unilateral lesions of the dorsolateral funiculus at levels ranging from T13 to L3. Unilateral lesions of the dorsolateral funiculus (DLF) produced significant ipsilateral decreases in stretch reflex threshold and increases in reflex gain, measured as incremental dynamic stiffness (IDS). ANCOVA testing indicated that the reduction in threshold, but not the increase in IDS, was dependent upon the level of background force. Reflex testing from different start angles demonstrated that DLF lesions diminished the correlation between threshold and IDS. Intravenous infusion of ketamine dose-dependently reduced IDS, compared with testing in the unanaesthetized state. Postoperative reflex testing during infusion of ketamine at 22.2 mg/kg per h, when electromyographic responses were reduced to 24% of control levels, abolished differences in IDS between the ipsilateral and contralateral hindlimbs. These and related observations suggest that the postoperative increase in IDS in awake animals was not due to an increase in passive stiffness. PMID- 9987040 TI - Differential brain expression of a new beta-actin gene from zebrafish (Danio rerio). AB - It has been shown that actin genes exhibit distinct tissue and stage-specific patterns of expression. We have cloned a new beta-actin gene from the teleost zebrafish (Danio rerio), a well-established model for developmental studies, and analysed its expression by Northern blot and in situ hybridization studies. Our results suggest that in adult brain zebrafish, this new gene is expressed during neuronal cell proliferation. PMID- 9987041 TI - The late open artery hypothesis at the crossroad. The ACTOR study: aggressive versus conservative treatment of the infarct-related artery after acute MI. ACTOR Study Group. AB - The purpose of this multicenter study is to test the hypothesis that opening an occluded infarct-related artery late after acute myocardial infarction in asymptomatic patients without evidence of residual ischemia would reduce cardiac events over three years of follow-up. The search for an explanation of the complex relationship between the patency of the infarct-related artery and the clinical evolution of the patient who suffered an infarction led to the open artery hypothesis, whose interpretation comprises two different components. The first component attributes the benefit to the fact that the timing and the method of reperfusion treatment induce a significant degree of myocardial salvage through early and persistent recanalization, and this is defined as the "time dependent component" of the patent artery hypothesis. The second component ascribes the clinical benefit to late recanalization in conditions in which intermittent, early, spontaneous or pharmacologically-induced recanalization is unequivocally absent, and this is called the "time-independent" component. There are numerous mechanisms by which the patency of the infarct-related artery may potentially influence clinical evolution independently of myocardial salvage. Reperfusion may increase the stiffness of the infarct zone, thus limiting its expansion and dilation. It is also possible that restoration of flow through the vascular bed may provide a sort of "scaffolding", which limits the expansion of the necrotic myocardium. Patency of the infarct-related artery has also been suggested to confer electrical stability to the infarct area and could be the source of a collateral blood flow, thereby protecting the myocardium against future coronary events. Even if these data support the hypothesis that patency of the infarct-related artery has beneficial effects with regard to both LV function and survival, they do not provide definite grounds to change treatment strategy in post-acute myocardial infarction by referring all patients with occluded infarct arteries for mechanical revascularization. Hence, there is widespread consensus that a randomized study conducted in an adequately-sized population with clinically meaningful endpoints would provide the necessary degree of certainty. The ACTOR study should plan analysis of the status of infarct artery patency after the acute phase of myocardial infarction, excluding those patients who require myocardial revascularization on a clinical-angiographic basis and randomly allocating the remaining patients for PTCA or conservative treatment. If intervention with PTCA and stent for these patients is demonstrated to reduce clinical events at three years, then a policy of routine angiography after the acute phase of MI with the intent of percutaneous catheter revascularization for totally occluded infarct arteries would be justified. PMID- 9987042 TI - Clinical utility and safety of exercise testing in patients with hypertrophic cardiomyopathy. AB - BACKGROUND: Exercise testing has long been employed in patients with hypertrophic cardiomyopathy (HCM), although concerns have constantly been expressed regarding its safety. This study reviews a large number of exercise tests performed in a community-based population with HCM, in terms of safety and clinical utility. METHODS: We analyzed a total of 243 maximal symptom-limited cycloergometer exercise tests performed at our institution in 138 patients with HCM (age 42 +/- 14 years, M/F 99/39), who were followed systematically for 9.4 +/- 6.5 years. RESULTS: In none of the 243 exercise tests did cardiac arrest, hemodynamic collapse or malignant arrhythmia occur, although 53 of the study patients (38%) had > or = 1 risk factors including previous cardiac arrest, recurrent syncope, malignant family history and resting left ventricular outflow obstruction. Early termination of the test was necessary in only 8 patients due to symptomatic hypotension with dizziness, but none had syncope. Mean predicted functional capacity achieved by the study group was 77 +/- 22%. Poor performance (< 60% of predicted functional capacity) was observed in 32 patients (23%), and it was associated with a NYHA functional class > 1 and an abnormal blood pressure response to exercise. Non-malignant arrhythmias occurred in 41 patients (30%), including multiple premature ventricular beats (PVB), paroxysmal atrial fibrillation, non-sustained ventricular (NSVT) and supraventricular tachycardia. The combined presence of multiple exercise-induced PVB and NSVT on Holter ECG had a 14% positive but a 97% negative predictive value for sudden death or cardiac arrest. CONCLUSIONS: 1) Exercise testing is safe in a community-based population of patients with HCM, and provides useful information regarding functional capacity, efficacy of treatment, blood pressure response to exercise and inducible ischemia. Thus, ergometry should routinely be included in the standard evaluation and follow-up protocols of HCM patients. 2) Conversely, the utility of ergometry in the evaluation of the arrhythmic risk in HCM patients appears to be limited to the identification of low-risk patients. PMID- 9987044 TI - "Hybrid" and combined percutaneous and surgical intervention to treat selected cardiac patients: a new strategy. AB - The term "hybrid revascularization" describes the combined use of minimally invasive surgery without cardiopulmonary bypass and percutaneous coronary revascularization in selected cases. The theoretical advantage of a less invasive surgical intervention must be weighted against the need for additional percutaneous procedures, with their own risks and limitations. We describe our initial experience with hybrid revascularization at the Istituto Clinico Humanitas in Milan. From 7/97 to 10/98, twelve patients underwent hybrid revascularization or a combined percutaneous and surgical intervention. A "classic" hybrid approach, consisting of minimally-invasive direct coronary artery bypass to the left anterior descending coronary artery and angioplasty or stenting of arteries in the right coronary artery or circumflex territories, was used in nine patients. In three patients, myocardial revascularization could be completed with percutaneous procedures after bypass surgery without cardiopulmonary bypass (in two patients because of severe aortic calcification) or valve surgery in a patient with two previous bypass operations. In-hospital complications were observed in three patients. Two required urgent median sternotomy (one for impending cardiac tamponade, one for conversion to bypass on extra-corporeal circulation). One patient developed atheroembolism after percutaneous intervention: after hospital discharge, there was a recurrence of symptoms, clinical deterioration with renal failure and eventually death. At a mean follow-up of 152 +/- 91 days (range 17 to 283) after minimally-invasive surgery and 166 +/- 122 days (range 13 to 397) after angioplasty, all surviving patients are well and free of anginal symptoms. Closer collaboration between surgical and interventional operators may offer a novel approach to effective treatment of difficult patient subsets. However, our initial experience suggests that a cautious evaluation of possible risks and benefits must carefully be entertained in each patient who may be considered a candidate for hybrid revascularization or combined percutaneous and surgical intervention. PMID- 9987043 TI - The extent of regional wall motion abnormalities identifies patients at risk of extensive left ventricular remodeling: implications for the design of post myocardial infarction trials. AB - BACKGROUND: The FAMIS (Fosinopril in Acute Myocardial Infarction Study) was a multicenter, placebo-controlled, double-blind trial designed to evaluate the safety and the efficacy of fosinopril in reducing left ventricular enlargement after acute anterior myocardial infarction. We evaluated the echocardiographic examinations performed during the trial in order to assess the trend of the remodeling process over time and to evaluate the role of infarct size in identifying patients at risk of progressive left ventricular dilation. METHODS: A complete echocardiographic examination was performed on admission, before discharge and three months later. Patients undergoing coronary bypass surgery or PTCA had a further examination prior to the procedure. The echocardiograms were analyzed at a central laboratory, and the end-diastolic and end-systolic left ventricular volumes were computed by using a modified Simpson's rule technique. Regional wall motion was evaluated using the centerline method, analyzing the left ventricular boundary along 100 chords perpendicular to the centerline constructed midway between the end-diastolic and the end-systolic contours. A quantitative infarct-size index was then computed according to the number of chords with a fractional shortening equal to or less than 5%. RESULTS: Left ventricular end-diastolic and end-systolic volume index significantly increased over time (p < 0.0001); as a result, the stroke volume increased (p < 0.0001) but the ejection fraction did not change. Patients were then divided according to the three-month infarct-size index. For both end-diastolic and end-systolic volume, not only did larger infarcts had higher volumes, but there was also a greater increase from baseline to 3 months. Moreover, larger infarcts had a lower ejection fraction, with a further reduction over the three months, while smaller infarcts had higher values and an increase over time. An infarct-size index of 25 or larger allowed prospective identification at the baseline examination of patients at risk of subsequent left ventricular dilation. CONCLUSIONS: In conclusion, patients at greatest risk of left ventricular dilation, namely those with larger infarct size, constitute a group that is worth considering for any therapeutic effort for reducing the remodeling process. These patients could in fact benefit from therapeutic strategies aimed at the reduction of left ventricular remodeling and should be studied in clinical trials. PMID- 9987045 TI - Influence of cigarette smoking on the electrocardiographic diagnosis of left ventricular hypertrophy in arterial hypertension. AB - Electrocardiography (ECG) has a lower sensitivity for the diagnosis of left ventricular (LV) hypertrophy in smokers than in non-smokers, but the explanation for this finding is not known. In the setting of the Progetto Ipertensione Umbria Monitoraggio Ambulatoriale (PIUMA) study, all subjects smoking > or = 15 cigarettes/day (n = 121, 89 men, age 48 +/- 11 years) were selected from 1443 untreated hypertensive subjects undergoing ECG and M-mode echocardiography, and matched with 484 hypertensive non-smokers by gender (same sex), age (+/- 5 years), and systolic and diastolic blood pressure (both +/- 5 mmHg) in a case-to control design with a 1:4 matching ratio. Smokers and non-smokers did not differ by age, gender, body mass index, and blood pressure. The voltage of SV1 + RV5 or V6 and RI (p < 0.05), but not of SV3 + RaVL, was lower in smokers. Sensitivity of ECG was lower in smokers when using peripheral or left precordial voltage criteria (e.g. 11 vs 26% for Sokolow-Lyon voltage). When using definitions based on different criteria (voltage of S wave in V3, LV axis, LV strain), sensitivity was not dissimilar in smokers and non-smokers (e.g. 19 vs 18% for Romhilt-Estes score, 40 vs 34% for Perugia criterion). Thus, in hypertensive smokers, sensitivity of ECG is lower than in non-smokers when using peripheral or left precordial voltage criteria, probably due to increased chest size in smokers resulting from increased lung compliance. For LV hypertrophy detection, Sokolow Lyon voltage should be avoided in hypertensive smokers and replaced by other criteria (Cornell voltage, Romhilt-Estes score, Perugia criterion), which are not influenced by cigarette smoking. PMID- 9987046 TI - Clinical impact of local implementation of agreed guidelines for the management of patients with acute myocardial infarction. AB - OBJECTIVE: This study sought to assess the impact of local implementation of clinical practice guidelines on the pattern of care and outcome in patients admitted to the Coronary Care Unit (CCU) with acute myocardial infarction. BACKGROUND: Development of clinical practice guidelines is among the most popular of the methods intended to promote translation of results from clinical trials into routine care. However, very little is known about the actual impact on routine care of the clinical guidelines for managing patients with acute myocardial infarction. METHODS: We reviewed a prospectively collected cohort of consecutive patients discharged with a diagnosis of acute myocardial infarction from S. Maria degli Angeli, a large community-based hospital in northeast Italy. Eighty-six patients treated in 1996 (before guideline implementation) were compared with 70 patients treated in 1997 (after guideline implementation) with respect to patterns of use of guideline-directed pharmacotherapies for acute myocardial infarction, diagnostic testing, length of CCU stay and clinical outcome. RESULTS: The two groups were similar in male gender, age, infarct location and severity. Patients managed before guideline implementation were less likely to receive thrombolysis (36 vs 50%; p = 0.05), i.v. beta-blockers at admission (13 vs 31%; p = 0.002), oral beta-blockers at CCU discharge (45 vs 74%; p = 0.0003). When these were given, patients managed before guideline implementation received lower dosages of i.v. heparin, as manifested by a lower proportion of patients reaching adequate aPTT levels at 24 hours (14 vs 62%, p < 0.0001), and of oral beta-blockers (-50%, p < 0.0001), and higher dosage of aspirin (+100%, p < 0.0001). The time to mobilization (+1 day) and the length of CCU stay (+0.5 day) were longer in patients managed before guideline implementation (p < 0.0001). Incidence of major complications was similar between the two groups (19 vs 13%, respectively; p = ns). CONCLUSIONS: Patients with myocardial infarction managed after local implementation of clinical practice guidelines were more likely to receive evidence-based effective pharmacotherapies, and to have earlier mobilization and earlier discharge from CCU. This study strongly supports the role of local implementation of clinical practice guidelines to optimize management of patients with acute myocardial infarction. PMID- 9987047 TI - [Electrocardiographic changes during at term labor]. AB - BACKGROUND: Electrocardiographic ST-changes are known to occur during pregnancy, puerperium and cesarean section or spontaneous labor under oxytocic, tocolytic and anesthetic treatment. The aim of the study was to detect ST-changes during spontaneous labor in healthy women, without anesthetic or oxytocic therapy, and to verify their relation to plasmatic electrolyte variations and other pathophysiologic factors. METHODS: Electrocardiograms were performed in 46 healthy women (age 30.4 +/- 6) at term pregnancy, during labor, 12-24 hours after delivery and then again three months after delivery. Hemochrome and sideremia were tested before labor and electrolytes (Na, K, Cl, Mg, Ca) were tested during each electrocardiogram. The patients were divided in two groups, patients with (group A) and without (group B) ST-changes. RESULTS: Before labor, three patients (7%) were in group A with nonspecific ST-changes (flat ST and/or fluctuating T wave) in precordial leads V2-V3-V4; group B had 43 patients (93%). During labor, group A included 27 patients (59%): 16 (59%) showed T inversion, 23 (85%) nonspecific changes, and eight (30%) had ST shift < or = 0.5 mm, in precordial and inferior leads. The three patients in group A before labor showed increased changes during labor. Group B had 19 patients (41%). Heart rate and blood pressure were within normal range in all patients. Early after delivery, seven patients out of 27 in labor were still in group A (15% of total) with nonspecific ST-changes; group B had 39 patients (85%). Three months after delivery, all patients were in group B. A drop in plasmatic K, detected during labor in all patients and returning to normal soon after delivery, was higher in group A than in group B (p < 0.01). CONCLUSIONS: ST-changes detectable during labor, similar to the ones described during pregnancy and puerperium but greater and more frequent, are independent of anesthetic and/or oxytocic treatment; they are not ischemic and disappear after delivery. They are related to the drop in plasmatic K, hyperventilation, hormonal changes, uterine contractions, O2-consumption and pain. PMID- 9987048 TI - [Incidence of carotid atherosclerosis in patients undergoing a coronarographic study. A prospective study of 193 patients]. AB - BACKGROUND: Many studies have identified the interrelationship between carotid artery disease (CD) and coronary artery disease (CAD). The purpose of this study was to evaluate the real incidence of CD, using an echo-duplex technique, in patients hospitalized for diagnostic coronary angiography. METHODS AND RESULTS: An ultrasound evaluation with echo-duplex of the carotid arteries was performed on 193 consecutive patients (152 males and 41 females) hospitalized for diagnostic coronary arteriography. Patients were divided into three groups: normal coronary angiography, coronary artery with stenosis < 70% (< 50% of left main), coronary artery with stenosis > or = 70% of a vessel (> or = 50% of left main). Carotid arteries were divided into normal arteries, arteries with stenosis < 50%, arteries with stenosis > or = 50% and < 70% and arteries with stenosis > or = 70%. Seventy-one patients had one-vessel disease, 42 had two-vessel disease and 49 had three-vessel disease (10 with left main disease). Out of 193 patients, 86 had CD and of these, 64 had a lumen stenosis < 50% and 22 a lumen stenosis > or = 50%. There was a strong correlation between the degree of carotid lumen stenosis and the extent of CAD. Carotid artery stenosis > or = 50% was present in 12.96% of the patients (21/162) with coronary stenosis > or = 70% of a vessel. In particular, 8.45% (6/71) and 9.52 (4/42) of patients with stenosis of 1 or 2 coronary vessels; 22.45% (11/49) with stenosis of 3 coronary vessels [40% (4/10) when the left main artery was involved]. CONCLUSIONS: Our study confirms the relatively high frequency of CD in patients with CAD and the correlation between the degree of carotid artery stenosis and the extent of CAD. This seems to justify the use of carotid echo-duplex investigation in patients hospitalized for diagnostic coronary angiography and indeed, it is mandatory before coronary revascularization (especially in aorta-coronary bypass). PMID- 9987049 TI - [Usefulness of atrial vulnerability in predicting atrial fibrillation in patients with sick sinus syndrome treated with DDD pacemaker]. AB - BACKGROUND: Atrial fibrillation (AF) is common in patients with sick sinus syndrome (SSS) treated with dual-chamber pacing and it may complicate their management. This study was undertaken to establish the usefulness of atrial vulnerability (AV), determined by means of transesophageal electrophysiological study (TES), in predicting the risk of developing AF and in deciding the type and program of pacemaker (PM) to be implanted in patients with SSS. METHOD: AV was assessed preoperatively using TES in 81 consecutive patients with SSS. AV (AF > 1 min) was divided into "low threshold" (induction with burst < or = 300/min) and "high threshold" (induction with burst > or = 350 min or with incremental ramp). The PM was programmed to ensure constant atrial capture in all patients. Follow up lasted three years. No patients received antiarrhythmic drugs. RESULT: AV was positive in 52% of patients (Group A) and negative in 48% of patients (Group B). A history of paroxysmal AF was present in 52% of patients in Group A and in 12% of patients in Group B. At follow-up, 38% of Group A and 2% of Group B patients had chronic AF. AV had sensitivity, specificity, positive predictive value (ppv) and negative predictive value (npv) of 94, 59, 38 and 97%, respectively. Thirty eight percent of patients showed low threshold vulnerability, with sensitivity, specificity, ppv and npv of 87, 92, 87 and 93%, respectively. Sensitivity, specificity, ppv and pnv for history of AF were 93, 100, 98 and 84%, respectively. When the vulnerability threshold and the history of paroxysmal AF were considered together, the sensitivity, specificity, ppv and npv was 94, 100, 100 and 83%, respectively. Multivariate analysis was shown to be an independent predictive value only for history of AF (p = 0.0002). CONCLUSION: AV determined by means of TES, especially with a low induction threshold, shows excellent sensitivity and specificity in evaluating the risk of chronic AF. It could be useful in patients with SSS undergoing cardiac pacing who have never had AF, thus allowing a more accurate choice of the type and program of PM to be implanted. Case histories of paroxysmal AF could represent useful criteria for selecting patients at a high risk of developing chronic AF. PMID- 9987050 TI - [Doppler tissue imaging: a new method in the study of diastolic function in left ventricular hypertrophy]. AB - BACKGROUND: Many factors influence diastolic function indexes obtained by monitoring left ventricular filling. Recent reports suggest that the study of myocardial wall velocity with Doppler tissue imaging (DTI) can give diastolic function parameters that are less affected by the same factors. An altered diastolic function has been demonstrated with invasive methods in patients with left ventricular hypertrophy (LVH). The aims of this study were 1) to compare a group of healthy subjects with a group of patients with LVH and presumably affected by diastolic dysfunction, to try to demonstrate if DTI could give new indexes to discriminate between the two groups; 2) to compare the indexes obtained with DTI against the ones given by Doppler study of left ventricular filling in the two populations. MATERIALS AND METHODS: Forty-two patients with LVH were compared to forty normal subjects. We studied the posterior wall velocity with pulsed DTI from parasternal view, measuring the early diastolic velocity (E'), the late diastolic velocity (A') and the E'/A' ratio. In addition, we estimated the usual ventricular filling parameters and the time interval between R wave of ECG and the peaks of E' and E waves. RESULTS: At left ventricular filling, patients with LVH showed an increase in A-wave peak velocity (mean 75.3 cm/s versus 66.4 cm/s; p < 0.05) and prolonged deceleration time (mean 216 ms versus 181 ms; p < 0.05), as compared to normal reference subjects. E-wave peak velocity and E/A ratio did not differ between the two groups. At DTI, patients with LVH had decreased early diastolic velocity (E') (mean 9 cm/s versus 12 cm/s; p < 0.05) and E'/A' ratio (mean 1.53 versus 1.91; p < 0.05) as compared to the control group. We observed an inverse correlation between E' wave and age in normal subjects. There was no correlation between the early diastolic myocardial velocity (E') and early inflow velocity (E) in both groups. A correlation was found between A and A' waves in normal subjects, but not in hypertrophic ones. The E'-wave peak always preceded the E-wave peak in all the subjects. CONCLUSION: Diastolic function indexes achieved by DTI can offer additional information that is independent of the data derived from left ventricular filling. PMID- 9987051 TI - Refractory angina despite patent coronary artery bypass grafts: treatment with transmyocardial laser revascularization and scintigraphic evidence of improved myocardial perfusion. AB - Progression of coronary artery disease that causes recurrent angina in patients who have already undergone coronary artery bypass grafting (CABG) is a challenge to cardiac surgeons. The presence of myocardial ischemia that is not due to bypass grafts occlusion, but to the quality of the coronary vessels characterized by diffuse atherosclerotic peripheral disease, makes the situation even more difficult, since it is not possible to perform myocardial revascularization either by percutaneous transluminal angioplasty (PTCA) or by means of new grafts. We report the case of a patient who, 4 years after triple CABG, developed refractory angina despite patency of bypass grafts (to left anterior descending artery, obtuse marginal branch and posterior descending) and maximally tolerated conventional medical treatment. Native coronary arteries were occluded. Because of the exiguous caliber of the distal portion of epicardial vessels and poor run off, a redo CABG was judged to be unfeasible. Transmyocardial laser revascularization (TMLR) was performed through left anterior thoracotomy, minimizing the risk of damage to the grafts. Clinical improvement (from CCS class IV to 0) and scintiscan showing improved myocardial perfusion to the laser treated regions confirm the effectiveness of TMLR in otherwise inoperable coronary artery disease. PMID- 9987052 TI - Autonomic neural control during acute myocardial ischemia after phenylephrine infusion and subsequent nitroglycerin-induced hypotension and bradycardia. AB - ST-elevation acute myocardial ischemia occurred after phenylephrine infusion in a patient with severe coronary artery disease and recent myocardial infarction. The subsequent administration of nitroglycerin led to a vasovagal response with symptomatic hypotension and bradycardia. During myocardial ischemia, heart-rate variability and baroreflex sensitivity analysis described a marked activation of sympathetic drive and severe impairment of baroreflex control. The nitroglycerin induced hypotension-bradycardia was associated with complex changes in the autonomic pattern characterized by subsequent phases of abrupt activation/deactivation of the two limbs of autonomic nervous system developing into a loss of neural control mechanisms. PMID- 9987053 TI - [Reversal left diastolic ventriculo-atrial flow induced by asynchronism in a patient with dilated cardiopathy and VVI pacemaker]. AB - We studied a case of reversal atrioventricular diastolic flow in a 74-year-old patient suffering from chronic heart failure for six years, following double myocardial infarction on the inferior (in 1985) and the anterior wall (in 1992). During his last hospitalization, he had an arrhythmic complication (advanced atrioventricular block) that required a definitive implantation of a VVI pacemaker. The patient, a working man in good hemodynamic condition over the past several years, acknowledged symptoms of progressive functional decline three to six months prior to coming to our observation for a medical check-up. The surface electrocardiogram showed normal electrical PM activity. Echo-Doppler examination beyond the improved systolic function of left ventricle showed a variable E/A velocity ratio of mitral valve flow, due to the casual relationship between spontaneous atrial electrical activity and ventricular stimulation. In addition, at the surface ECG we frequently observed a retrograde atrioventricular flow during mean phase of diastole each time the P wave occurred at the end of T wave. This event did not occur when the T-P interval was longer (a few more milliseconds) and was thus similar to a normal atrioventricular ECG sequence. To summarize, we can affirm that in patients with dilated cardiomyopathy and improved systolic function requiring pacemaker implantation, the sequential mode of ventricular stimulation must be preferred, especially if there is normal electrical activity in the right atrium. PMID- 9987054 TI - [If it is supposed to be specialization, make it true specialization]. PMID- 9987055 TI - [Individual pressure profile in clinical practice]. PMID- 9987056 TI - Voluntary movements and event-related potentials in Parkinsonians (stages 1-2). AB - The temporal analysis of goal-directed movements has revealed that the delay of movement initiation in Parkinsonians might be decreased or abolished by altering the preparatory set and increasing the motivation level of patients. Averaged event-related potentials (ERPs) during different psychomotor reactions to light stimuli, ignore condition and difference waves between attend (reactions) and ignore conditions were analyzed in 19 Parkinsonian patients (stages 1-2) and 12 healthy subjects. A deceleration of psychomotor reactions in the patients was found to be accompanied by a decrease in ERPs, especially in frontal recording. This decrease was affected by an altered pre-stimulus preparatory set in the patients. The decrease of endogenous ERPs (difference waves) was associated to a greater extent with the motor acts than with cognitive operations. The deceleration of the voluntary movements in Parkinsonism is assumed to be connected with 'deficit' of the frontal activation due to a dysfunction of the basal ganglia. PMID- 9987057 TI - Effects of race, sex, and socioeconomic status upon cardiovascular stress responsivity and recovery in youth. AB - Cardiovascular (CV) responsivity to and recovery from acute laboratory stressors, as derived from aggregate scores of CV functioning during and after postural change, video game challenge, social competence interview, and parent-child conflict discussion, were evaluated in 272 youths [mean age 13.5 +/- 2.6 years; 162 Blacks (77 males, 85 females), 110 Whites (60 males, 50 females)], all with a positive family history of essential hypertension. Blacks demonstrated greater systolic and diastolic blood pressure (SBP, DBP) and lower heart rate responsivity compared to Whites (all P values < 0.05). A race by neighborhood socioeconomic status (SES) interaction for SBP responsivity was also observed where low SES Whites and high SES Blacks had the greatest responsivity compared to their same race cohorts. Additionally, upper SES Whites had the lowest total peripheral resistance responsivity. For recovery, Blacks and males exhibited higher SBP during recovery compared to Whites and females, respectively. These findings extend previous studies and provide further support for the hypothesis that recovery from stress is a potentially informative component of the contribution of stress responsivity to cardiovascular disease. PMID- 9987058 TI - Changes in pupil reaction to light in melancholic patients. AB - The aim of the current study was to compare the pupil reaction to light in depressed patients and normal control subjects. Seven depressed patients with melancholic features according to DSM-IV criteria and 14 age- and gender-matched control subjects took part in the study. All were free of any medication for at least 2 weeks. All were aged between 25 and 50 years. An optical method was used to assess the pupil reaction to a single flash. Depressed patients manifested shorter latency for constriction than control subjects, and a marginal difference in the total work produced by acetylcholine. The results of the current study support the theory that there is a norepinephrine hypoactivity in melancholic depression, with less affected acetylcholine activity. PMID- 9987059 TI - Electrophysiological, behavioral, and subjective indexes of workload when performing multiple tasks: manipulations of task difficulty and training. AB - This study examined whether alpha event-related desynchronization (ERD) and theta event-related synchronization (ERS) could successfully measure changes in cognitive workload and training while an operator was engaged in a continuous, interactive, control task(s). Alpha 1 (8-10 Hz) ERD, alpha 2 (10-12 Hz) ERD, and theta (3-7 Hz) ERS were determined for a communications event that occurred during multiple task workload conditions or as a single task. Other measures (alpha and theta EEG power, heart rate, respiration, eye blinks, behavioral performance, and subjective workload ratings) were also evaluated. Results showed that alpha 2 EEG, heart rate, behavioral, and subjective measures were sensitive to changes in workload in the multiple tasks. In addition, eye blink rate and behavioral measures were sensitive to training. Alpha ERD and theta ERS were not sensitive to workload and training in our interactive, multiple task environment. However, they were effective indexes of cognitive/behavioral demands within an interactive single task. PMID- 9987060 TI - The influence of psychotic states on the autonomic nervous system in schizophrenia. AB - Abnormal autonomic activity in patients with schizophrenia has been reported, but how psychotic states influence the autonomic nervous system (ANS) has remained unclear due to methodological limitations. The influence of psychotic states on ANS activity in patients with schizophrenia was investigated using a recently developed method of analysis based on heart rate variability which assesses cardiac sympathetic and parasympathetic function separately. Cardiac autonomic function (CAF), together with psychotic states, was assessed at the beginning and the end of an 8-week study period in 53 patients with chronic schizophrenia. The CAF in age- and sex-matched control subjects was also examined. There were no significant differences between the patients and the control subjects in the mean R-R interval (RRI) or in the indices of the sympathetic and the parasympathetic function. In the patients who changed in psychotic states, the parasympathetic index was significantly decreased without significant changes in the sympathetic index when their psychotic states were more pronounced, suggesting psychotic states suppressed the parasympathetic function without affecting the sympathetic function. In these patients, the mean RRI was smaller when their psychotic states were more pronounced. Our results demonstrate that psychotic states affect the ANS, suggesting a relationship between cerebral cognitive and peripheral ANS activities, and that this is presumably mediated through the parasympathetic nervous system. These findings are discussed in comparison with previous reports on the CAF in schizophrenia. PMID- 9987061 TI - Dealing with baseline differences: two principles and two dilemmas. AB - Two principles are presented that describe directional confounds associated with baseline differences: Principle 1: Change scores are confounded with baseline whenever data are skewed. Principle 2: When baseline differences are real, ANCOVA has a directional bias that magnifies differences in one direction and masks those in the other direction. Both principles involve a directional bias that is related to the direction of baseline difference and the direction of the hypothesized difference in change. Ethical dilemmas arise if decisions (whether or not to transform, whether or not to use ANCOVA) are chosen in order to maximize power by capitalizing on the directional bias and Type 1 error. PMID- 9987062 TI - P300, handedness, and corpus callosal size: gender, modality, and task. AB - The P300 event-related potential (ERP) was elicited in left- and right-handed young adult male and female subjects (n = 20/group), with auditory and visual stimulus modalities from single-stimulus and oddball tasks. P300 amplitude was larger across all conditions for left- compared to right-handed subjects at anterior and central electrode sites. P300 latency was shorter across all conditions for left- compared to right-handers. Task type did not affect the ERP handedness differences. Male and female subjects demonstrated comparable ERP handedness effects, although smaller P300 components were obtained for males compared to females. When considered in the context of previously reported corpus callosal size differences for left- vs. right-handed and male vs. female participants, the findings suggest that the P300 reflects callosal size and inter hemispheric transmission efficacy. PMID- 9987063 TI - Risk for hypertension and diminished pain sensitivity in women: autonomic and daily correlates. AB - Research suggests an association between risk for hypertension and decreased pain sensitivity. However, few studies have utilized non-behavioral indices of pain to corroborate subjective reports or sought to generalize these findings to women. Furthermore, it has not been established whether results obtained using well controlled laboratory pain stimuli extend to naturalistic pain. In Study 1, 80 young adult women with (N = 40) and without (N = 40) a parental history of hypertension and with either normatively low or high resting systolic blood pressure (SBP) were exposed to two experimental pain stimuli, finger pressure and the cold pressor test. In addition to behavioral pain measures, respiratory sinus arrhythmia (RSA) reactions to pain were also assessed. Women with a parental history of hypertension and/or normatively high resting SBP experienced significantly less pain, as assessed by both behavioral and RSA measures. In Study 2, 37 of the participants from Study 1 monitored their behaviors, affect, and physical symptoms, three times a day for 32 days. Laboratory pain sensitivity was significantly correlated with daily reports of pain but not gastrointestinal symptoms. The present results confirm an association between risk for hypertension and hypoalgesia in women and suggest generalizability of this relationship to everyday life. PMID- 9987064 TI - Alterations in nonenzymatic biochemistry in uremia: origin and significance of "carbonyl stress" in long-term uremic complications. AB - Advanced glycation end products (AGEs), formed during Maillard or browning reactions by nonenzymatic glycation and oxidation (glycoxidation) of proteins, have been implicated in the pathogenesis of several diseases, including diabetes and uremia. AGEs, such as pentosidine and carboxymethyllysine, are markedly elevated in both plasma proteins and skin collagen of uremic patients, irrespective of the presence of diabetes. The increased chemical modification of proteins is not limited to AGEs, because increased levels of advanced lipoxidation end products (ALEs), such as malondialdehydelysine, are also detected in plasma proteins in uremia. The accumulation of AGEs and ALEs in uremic plasma proteins is not correlated with increased blood glucose or triglycerides, nor is it determined by a decreased removal of chemically modified proteins by glomerular filtration. It more likely results from increased plasma concentrations of small, reactive carbonyl precursors of AGEs and ALEs, such as glyoxal, methylglyoxal, 3-deoxyglucosone, dehydroascorbate, and malondialdehyde. Thus, uremia may be described as a state of carbonyl overload or "carbonyl stress" resulting from either increased oxidation of carbohydrates and lipids (oxidative stress) or inadequate detoxification or inactivation of reactive carbonyl compounds derived from both carbohydrates and lipids by oxidative and nonoxidative chemistry. Carbonyl stress in uremia may contribute to the long-term complications associated with chronic renal failure and dialysis, such as dialysis-related amyloidosis and accelerated atherosclerosis. The increased levels of AGEs and ALEs in uremic blood and tissue proteins suggest a broad derangement in the nonenzymatic biochemistry of both carbohydrates and lipids. PMID- 9987065 TI - The development of x-ray imaging to study renal function. AB - The well-established role of the kidney in control of blood volume and ultimately arterial blood pressure has been underscored by the demonstration of alterations in renal hemodynamics and function recognized as responsible for these and other regulatory mechanisms. Nevertheless, the spatial complexity of intrarenal structure and function has made evident the need to study these separately in different regions of the intact kidney. Because of the introduction of x-rays, assessment of renal function has indeed been one of their attractive applications. However, despite the appeal of their noninvasiveness, several limitations confounded the different x-ray techniques used, most of which remained unresolved until the development of computed tomography. Furthermore, the development of fast imaging, which allows repetitive analysis of the same region of interest during the transit of contrast medium, holds a great potential to estimate intrarenal distribution of blood flow and the dynamic characteristics of tubular fluid flow in individual nephron segments. This latter assessment requires the administration of filterable x-ray contrast medium, which is cleared from the plasma almost exclusively by glomerular filtration, and the generation of contrast dilution curves. A historical review of the development and progress of the various x-ray techniques used will help understand the past and present of x-ray imaging, and will make it easier to envision the importance of their future roles in the study of renal physiology and pathophysiology. PMID- 9987066 TI - Flaxseed ameliorates interstitial nephritis in rat polycystic kidney disease. AB - BACKGROUND: Flaxseed has demonstrated useful antiinflammatory properties in a number of animal models and human diseases. We undertook a study to determine if flaxseed would also modify clinical course and renal pathology in the Han:SPRD-cy rat. METHODS: Male Han:SPRD-cy rats were pair fed a 10% flaxseed of control rat chow diet for eight weeks from weaning. Tissue was harvested for analysis of cystic change, apoptosis, cell proliferation, and fibrosis. Tissue was also harvested for lipid analysis using gas chromatography. RESULTS: Animals thrived on both diets. Flaxseed-fed animals had lower serum creatinine (69 vs. 81 mumol/liter, P = 0.02), less cystic change (1.78 vs. 2.03 ml/kg, P = 0.02), less renal fibrosis (0.60 vs. 0.93 ml/kg, P = 0.0009), and less macrophage infiltration (13.8 vs. 16.7 cells/high-power video field) of the renal interstitium than controls. The groups did not differ in renal tubular epithelial cell apoptosis and proliferation. Lipid analysis revealed significant renal enrichment of 18 and 20 carbon omega 3 polyunsaturated fatty acids (total omega 6:omega 3 ratio 3.6 vs. 9.1, P < 0.0001). CONCLUSIONS: Flaxseed ameliorates Han:SPRD-cy rat polycystic kidney disease through moderation of the associated chronic interstitial nephritis. The diet alters renal content of polyunsaturated fatty acids in a manner that may promote the formation of less inflammatory classes of renal prostanoids. PMID- 9987067 TI - Intrauterine growth restriction is associated with persistent juxtamedullary expression of renin in the fetal kidney. AB - BACKGROUND: Intrauterine growth restriction (IUGR) has been linked to impaired renal function and hypertension, suggesting that an adverse prenatal environment could alter kidney development and renin production. METHODS: Immunohistochemistry and in situ hybridization were employed to localize renin containing cells (RCCs) in the deep, middle, and superficial zones of autopsy kidney sections, in parallel with histologic maturation, from unexplained stillborn fetuses of normal weight (N = 26) and stillborn fetuses with IUGR (N = 17). RESULTS: In the control group, the number of RCC per 100 glomeruli in the deep zone decreased with advancing gestation from 40 at 20 weeks gestation to five at term (P < 0.001), whereas the opposite change was found in the superficial zone (increase from 5 per 100 to 55 per 100; P < 0.001). In the IUGR group, the density of RCCs in both the superficial and deep zones was similar to the control group at 20 weeks, and no shift in renin gene expression was observed as gestation advanced. Histologic maturation was unaltered. CONCLUSIONS: Renin gene expression persists and predominates in the deep renal cortex of the stillborn IUGR fetus, and could contribute to the pathogenesis of neonatal oliguria and/or hypertension during postnatal life. PMID- 9987068 TI - Cyclooxygenase metabolites mediate glomerular monocyte chemoattractant protein-1 formation and monocyte recruitment in experimental glomerulonephritis. AB - BACKGROUND: Monocyte chemoattractant protein-1 (MCP-1) has been shown to play a significant role in the recruitment of monocytes/macrophages in experimental glomerulonephritis. Whereas a number of inflammatory mediators have been characterized that are involved in the expression of MCP-1 in renal disease, little is known about repressors of chemokine formation in vivo. We hypothesized that cyclooxygenase (COX) products influence the formation of MCP-1 and affect inflammatory cell recruitment in glomerulonephritis. METHODS: The effect of COX inhibitors was evaluated in the antithymocyte antibody model and an anti glomerular basement membrane model of glomerulonephritis. Rats were treated with the COX-1/COX-2 inhibitor indomethacin and the selective COX-2 inhibitors meloxicam and SC 58125. Animals were studied at 1 hour, 24 hours, and 5 days after induction of the disease. RESULTS: Indomethacin, to a lesser degree the selective COX-2 inhibitors, enhanced glomerular MCP-1 and RANTES mRNA levels. Indomethacin enhanced glomerular monocyte chemoattractant activity an the infiltration of monocytes/macrophages at 24 hours and 5 days. CONCLUSIONS: Our studies demonstrate that COX products may serve as endogenous repressors of MCP-1 formation in experimental glomerulonephritis. The data suggest that COX-1 and COX 2 products mediate these effects differently because the selective COX-2 inhibitors had less influence on chemokine expression. PMID- 9987069 TI - Up-regulation of hepatocyte growth factor receptor: an amplification and targeting mechanism for hepatocyte growth factor action in acute renal failure. AB - BACKGROUND: Hepatocyte growth factor (HGF) and its c-met receptor comprise a signaling system that has been implicated in tissue repair and regeneration. HGF action is specifically targeted to the damaged organ following injury; however, the mechanism underlying this important targeting process remains to be elucidated. We reasoned that induction of c-met expression might be a critical factor in determining the site specificity of this receptor-ligand system. To test this hypothesis, we examined changes in activity of the HGF/c-met system in the folic acid model of acute tubular injury and repair. METHODS: Tissue HGF and c-met mRNA levels were detected by RNase protection assay and Northern blot analysis following acute renal injury induced by a single injection of folic acid. HGF and c-met proteins were examined by a specific enzyme immunoassay and Western blotting, respectively. C-met expression and trans-activation were investigated by exposing renal epithelial mIMCD-3 cells to various cytokines in vitro. RESULTS: Extremely rapid induction of renal HGF and c-met mRNA was observed beginning one hour following injection of folic acid. Circulating plasma HGF protein level rose dramatically (approximately 16-fold), peaking first at two hours and again at 24 hours following injection. Despite elevated HGF mRNA in the kidney, total kidney HGF protein actually decreased significantly at 24 hours following injury. On the other hand, both c-met mRNA and c-met protein were markedly increased in the kidney, where active renal tubule repair and regeneration take place. In vitro studies suggested that increased levels of HGF, as well as other cytokines, might account for enhanced c-met expression in renal tubular epithelial cells. Pretreatment of the cells with actinomycin D totally blocked c-met induction, suggesting that induced c-met expression occurs primarily at the transcriptional level. Using a cloned region of the c-met promoter coupled to a reporter gene, we demonstrated that HGF directly stimulated c-met promoter transactivation in renal epithelial cells. CONCLUSION: These results suggest that local up-regulation of c-met transcription in the kidney is crucial to renal tubule repair and regeneration, not only because it increases overall activity of this receptor-ligand system, but also as a mechanism targeting HGF action specifically to renal epithelia. PMID- 9987070 TI - Molecular mechanisms of glucose action on angiotensinogen gene expression in rat proximal tubular cells. AB - BACKGROUND: Clinical studies have shown that the angiotensin-converting enzyme (ACE) inhibitors or angiotensin II (Ang II) receptor antagonists decrease proteinuria and slow the progression of nephropathy in diabetes, indicating that Ang II plays an important role in the development of nephropathy. We have previously reported that high levels of glucose stimulate the expression of rat angiotensinogen (ANG) gene in opossum kidney (OK) proximal tubular cells. We hypothesized that the stimulatory effect of D(+)-glucose on the expression of the ANG gene in kidney proximal tubular cells is mediated via de novo synthesis of diacylglycerol (DAG) and the protein kinase C (PKC) signal transduction pathway. METHODS: Immortalized rat proximal tubular cells (IRPTCs) were cultured in monolayer. The stimulatory effect of glucose on the activation of polyol pathway and PKC signal transduction pathway in IRPTCs was determined. The immunoreactive rat ANG (IR-rANG) in the culture medium and the cellular ANG mRNA were measured with a specific radioimmunoassay and a reverse transcription-polymerase chain reaction assay, respectively. RESULTS: D(+)-glucose (25 mM) markedly increased the intracellular levels of sorbitol, fructose, DAG, and PKC activity as well as the expression of IR-rANG and ANG mRNA in IRPTCs. These stimulatory effects of D(+)-glucose (25 mM) were blocked by an inhibitor of aldose reductase, Tolrestat. PKC inhibitors also inhibited the stimulatory effect of D(+)-glucose (25 mM) on the expression of the IR-rANG in IRPTCs. The addition of phorbol 12-myristate 13 acetate further enhanced the stimulatory effect of D(+)-glucose (25 mM) on the expression of the IR-rANG in IRPTCs and blocked the inhibitory effect of Tolrestat. CONCLUSION: These studies suggest that the stimulatory effect of a high level of D(+)-glucose (25 mM) on the expression of the ANG gene in IRPTCs is mediated, at least in part, via the de novo synthesis of DAG, an activator of PKC signal transduction pathway. PMID- 9987071 TI - Gene therapy by transforming growth factor-beta receptor-IgG Fc chimera suppressed extracellular matrix accumulation in experimental glomerulonephritis. AB - BACKGROUND: The evidence that transforming growth factor-beta (TGF-beta) is a key mediator in the pathogenesis of fibrotic diseases is now supported by several lines of investigation. This evidence provides a certain base for targeting TGF beta as an antifibrotic agent. METHODS: We generated a chimeric cDNA, termed TGF beta RII/Fc, encoding an extracellular domain of the TGF-beta type II receptor fused to the IgG-Fc domain, and tested whether TGF beta RII/Fc could be a novel strategy for treating glomerular diseases. RESULTS: In cultured BNul-7 cells, recombinant TGF beta RII/Fc reversed the antiproliferative response induced by TGF-beta 1. In addition, TGF beta RII/Fc diminished the TGF-beta 1-induced production of EIIIA-positive fibronectin in cultured normal rat kidney cells. We then introduced the chimeric cDNA into the muscle of the nephritic rats by the hemagglutinating virus of Japan liposome-mediated gene transfer method in order to block the TGF-beta activity in nephritic glomeruli through systemic delivery of chimeric molecules. Treatment with TGF beta RII/Fc gene transfection could suppress the glomerular TGF-beta mRNA in nephritic rats with a comparable effect in the reduction of extracellular matrix accumulation. CONCLUSION: TGF beta RII/Fc successfully inhibited the action of TGF-beta in vitro and in vivo, and gene therapy by chimeric TGF beta RII/Fc might be feasible for the therapy of glomerulosclerosis. PMID- 9987072 TI - Activation of mesangial cell signaling cascades in response to mechanical strain. AB - BACKGROUND: Mesangial cells (MCs) are constantly exposed to pulsatile stretch and relaxation in their role as architectural support for the glomerulus. There is no cell proliferation in normal glomeruli. In contrast, animal models of increased glomerular capillary pressure are characterized by resident glomerular cell proliferation and elaboration of extracellular matrix (ECM) protein, resulting in glomerulosclerosis. This process can be ameliorated by maneuvers, such as angiotensin converting enzyme inhibition, that reduce glomerular capillary pressure. MCs grown on ECM-coated plates and exposed to cyclic stretch/relaxation proliferate and produce ECM protein, suggesting that this may be a useful in vitro model for MC behavior in response to increased physical forces. Previous work has shown induction of c-fos in response to application of mechanical strain to MCs, which may induce increases in AP-1 transcription factor activity, which, in turn, may augment ECM protein and transforming growth factor beta transcription and cell proliferation. Stimuli that lead to c-fos induction pass through mitogen-activated protein kinase (MAPK) pathways. Three MAPK cascades have been characterized in mammalian cells--p44/42 (classic MAPK), the stress activated protein kinase/Jun terminal kinase (SAPK/JNK) pathway, and p38/HOG--and mechanical strain activates p44/42 and SAPK/JNK in cardiac fibroblasts. However, in contrast to MCs, these cells do not proliferate in response to physical force. Accordingly, we studied activation of the MAPK pathways in MCs exposed to mechanical strain. METHODS: MCs (passages 5 to 10) cultured on type 1 collagen coated, flexible-bottom plates were exposed to 30, 60, or 120 minutes of cyclic strain (60 cycles/min) by computer-driven generation of vacuums of -14 and -28 kPa, inducing 20% and 29% elongations in the diameter of the surfaces, respectively. Control MCs were grown on coated rigid bottom plates. Proliferation was assessed at 24 hours by 3H-thymidine incorporation. Protein levels (by Western blot) and activity assays for all three kinase cascades were performed at 30, 60, and 120 minutes. RESULTS: Cyclic strain/relaxation lead to an approximate doubling of 3H-thymidine incorporation at 24 hours (N = 3, P < 0.05) only in cultures stretched 29%, but not in cultures stretched 20%. At -29% elongation, the increase in 3H-thymidine incorporation was preceded by early activation of MAPK signaling pathways. p44/42 activity increased to a maximum of eightfold greater than control at 60 minutes. p38/HOG activity was not measurable at baseline but was increased markedly at 30 minutes, which was sustained through to 120 minutes. SAPK/JNK activity was present at a very low level in MCs and was not changed by stretch. However, it was markedly increased by sorbitol. In MCs stretched to 20% elongation, lesser increases in p44/42 were seen with a similar time course, whereas no increases in p38/HOG or SAPK could be detected at the time points studied. No increase in any kinase pathway activity was seen at any time in static cultures. CONCLUSIONS: High-pressure cyclic stretch leads to MC proliferation, preceded by marked activation of p44/42 and p38/HOG MAPKs. Cell proliferation is not seen with low-pressure stretch, and there is only modest p44/42 MAPK activation, suggesting that glomerular capillary hypertension may lead to cell proliferation and injury partly through differential activation of kinase cascades. PMID- 9987073 TI - High glucose alters the response of mesangial cell protein kinase C isoforms to endothelin-1. AB - BACKGROUND: High glucose causes glomerular mesangial growth and increased matrix synthesis contributing to diabetic glomerulopathy. Our purpose was to determine if high glucose alters endothelin-1 (ET-1) or platelet-derived growth factor-B activation of mesangial cell diacylglycerol-sensitive protein kinase C (PKC) isoforms and subsequent stimulation of mitogen-activated protein kinase (MAPK; p42, p44). METHODS: Rat mesangial cells in primary culture were growth arrested for 48 hours in glucose 5.6 mM (NG) or 30 mM (HG). PKC-alpha, PKC-delta, and PKC epsilon translocation from the cytosol-to-membrane and cytosol-to-particulate (cytoskeleton, nucleus) cellular fractions were measured by immunoblot using isoform-specific monoclonal antibodies. PKC isoforms were visualized also by confocal immunofluorescence microscopy. MAPK activation was measured by immunoblot using phospho-MAPK antibody and by detection of Elk-1 fusion protein phosphorylation following phospho-MAPK immunoprecipitation. RESULTS: In NG, ET-1 stimulated cytosol-to-membrane translocation of PKC-delta and PKC-epsilon but not PKC-alpha. In HG, the pattern of ET-1-stimulated PKC-delta and PKC-epsilon changed to a cytosol-to-particulate distribution, which was confirmed by confocal immunofluorescence imaging. Platelet-derived growth factor-B did not cause translocation of PKC-alpha, PKC-delta, or PKC-epsilon in either NG or HG. In HG, both basal and ET-1-stimulated MAPK activities were increased significantly. In HG, down-regulation of PKC isoforms with phorbol ester prevented the increased stimulation of MAPK by ET-1. CONCLUSION: In HG, the enhanced activation of mesangial cell MAPK by ET-1 is PKC dependent and associated with altered translocation of PKC-delta and PKC-epsilon. Enhanced mesangial cell signaling responsiveness to vasoactive peptides in HG may constitute an important mechanism contributing to diabetic nephropathy. PMID- 9987074 TI - Effects of new analogues of vitamin D on bone cells: implications for treatment of uremic bone disease. AB - BACKGROUND: The use of calcitriol in the treatment of uremic hyperparathyroidism and renal osteodystrophy is limited in many patients by hypercalcemic side effects. New less calcemic analogues of calcitriol are being developed, and some are under clinical evaluation. To investigate whether these compounds possess important differences in their action on bone cells, we have studied their effects [with and without parathyroid hormone (PTH)] on the release and synthesis of the resorptive osteotropic cytokine, interleukin-6 (IL-6). METHODS: MG 63 and SaOS-2 human osteoblastic cell lines were cultured for 6 or 24 hours in media containing calcitriol, the sterols of interest, or 1-34 synthetic PTH. IL-6 release was assayed by commercially available enzyme-linked immunosorbent assay. IL-6 mRNA levels were assessed by reverse transcriptase-polymerase chain reaction. RESULTS: We found that calcitriol and paricalcitol behaved in a similar fashion, resulting in increased IL-6 release only at higher concentrations (10( 7) to 10(-9) M). In contrast, 22-oxacalcitriol and 1,25 dihydroxydihydrotachysterol2 stimulated release to a similar extent but at concentrations three to four orders of magnitude lower (10(-11) to 10(-13) M), despite being less potent as suppressers of parathyroid function than calcitriol. Studies of IL-6 mRNA showed a similar pattern of concentration and cell line dependent transcription. CONCLUSIONS: Compounds stimulating IL-6 release at concentrations achievable during the treatment of uremic hyperparathyroidism might favor continuing linked bone formation and resorption and thereby avoid adynamic bone disease while still allowing profound suppression of PTH. PMID- 9987075 TI - Endothelin receptor antagonists influence cardiovascular morphology in uremic rats. AB - BACKGROUND: In is generally held that renal failure results in blood pressure (BP)-independent structural changes of the myocardium and the vasculature. The contribution, if any, of endothelin (ET) to these changes has been unknown. METHODS: We morphometrically studied random samples of the left ventricle myocardium and small intramyocardial arteries in subtotally (5/6) nephrectomized (SNx) male Sprague-Dawley rats treated with either the selective ETA receptor antagonist BMS182874 (30 mg/kg/day) or the nonselective ETA/ETB receptor antagonist Ro46-2005 (30 mg/kg/day) in comparison with either sham-operated rats, untreated SNx, or SNx rats treated with the angiotensin-converting enzyme inhibitor trandolapril (0.1 mg/kg/day). RESULTS: Eight weeks later, systolic BP was lower in trandolapril-treated SNx compared with untreated SNx animals. No decrease in BP was seen following either ET receptor antagonist at the dose used. A significantly increased volume density of the myocardial interstitium was found in untreated SNx rats as compared with sham-operated controls. Such interstitial expansion was prevented by trandolapril and either ET receptor antagonist. SNx caused a substantial increase in the wall thickness of small intramyocardial arteries. The increase was prevented by trandolapril or BMS182874 treatment. The arteriolar wall:lumen ratio was significantly lower in all treated groups when compared with untreated SNx. In contrast, only trandolapril, but not the ET receptor antagonists, attenuated thickening of the aortic media in SNx animals. CONCLUSIONS: The ETA-selective and ETA/ETB-nonselective receptor antagonists appear to prevent development of myocardial fibrosis and structural changes of small intramyocardial arteries in experimental chronic renal failure. This effect is independent of systemic BP. PMID- 9987076 TI - Collagen secretion and growth of mesangial cells require geranylgeranylpyrophosphate. AB - BACKGROUND: The mevalonate pathway is important for the biosynthesis of isoprenoids such as geranylgeranylpyrophosphate (GGPP) and farnesylpyrophosphate, as well as cholesterol. It has been reported that treatment with 3-hydroxy-3 methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor ameliorates glomerular injury in several experimental models of progressive glomerular disease. However, the effect of HMG-CoA reductase inhibitor on mesangial cell function has not been fully understood. This investigation was performed to elucidate the role of a mevalonate metabolite(s) in mesangial cell proliferation and extracellular matrix accumulation. METHODS: Cycling or quiescent human mesangial cells were incubated in RPMI 1640 containing 10% heat-inactivated fetal calf serum (FCS) in the absence or presence of pravastatin, an inhibitor of HMG-CoA reductase, and mevalonate metabolites. Type IV collagen secretion, mRNA expression, and [3H]thymidine incorporation were measured. Cell cycle phases were monitored by flow cytometry. RESULTS: Pravastatin inhibited FCS-stimulated type IV collagen secretion (IC50 = 210 microM) and mRNA expression. Pravastatin also inhibited FCS stimulated [3H]thymidine incorporation (IC50 = 430 microM). Analysis with flow cytometry revealed that pravastatin inhibited the G1 to S phase transition of FCS stimulated mesangial cells. Mevalonate reversed these inhibitory effects of pravastatin completely. Among two major metabolites of mevalonate, GGPP and farnesylpyrophosphate, only GGPP reversed pravastatin-induced inhibition of type IV collagen secretion, DNA synthesis, and the G1 to S phase progression. CONCLUSIONS: These results suggest that GGPP plays critical roles for the type IV collagen secretion and G1 to S phase transition in FCS-stimulated human mesangial cells. PMID- 9987077 TI - Direct lysosomal uptake of alpha 2-microglobulin contributes to chemically induced nephropathy. AB - BACKGROUND: An abnormal accumulation of alpha 2-microglobulin (alpha 2 mu) in kidney lysosomes of male rats has been described in the nephropathy resulting from exposure to a variety of chemicals. The increment in lysosomal levels of alpha 2 mu cannot be explained by a decrease in its proteolytic susceptibility. Because a portion of alpha 2 mu resides in the cytosol of kidney cells, we decided to analyze whether this cytosolic form also contributes to the abnormal lysosomal accumulation of alpha 2 mu after exposure to chemicals. METHODS: Intact kidney lysosomes were isolated from untreated or 2,2,4-trimethylpentane (TMP) treated rats, and their ability to take up alpha 2 mu was compared. RESULTS: alpha 2 mu can be directly transported into isolated lysosomes in the presence of the heat shock cognate protein of 73 kDa (hsc73). alpha 2 mu specifically binds to a lysosomal membrane glycoprotein of 96 kDa, previously identified as the receptor for the hsc73-mediated lysosomal pathway of protein degradation. In rats exposed to TMP, the specific lysosomal transport of alpha 2 mu increases, as well as the ability of lysosomes to directly transport other substrates for this pathway. The increased lysosomal transport is mainly due to an increase in the levels of the receptor protein in the lysosomal membrane. CONCLUSIONS: The hsc73 mediated lysosomal pathway contributes to the normal degradation of alpha 2 mu in rat kidney and liver, and the activity of this pathway is increased after exposure to TMP. Our results suggest that the chemically induced accumulation of cytosolic alpha 2 mu in lysosomes is mediated by an increased rate of direct uptake into lysosomes. PMID- 9987078 TI - Effect of recombinant human erythropoietin on endothelial cell apoptosis. AB - BACKGROUND: Recombinant human erythropoietin (rHuEPO) induces endothelial cell growth and angiogenesis in vitro. The mechanisms are unknown. Because an increase in endothelial cell survival could play a role in this process, we examined the effect of rHuEPO on lipopolysaccharide (LPS)-induced apoptosis in bovine pulmonary artery endothelial cells (BPAECs). METHODS: Four groups of cells were studied. The first group was preincubated in serum-free medium followed by treatment with LPS. The second group was preincubated with rHuEPO followed by LPS. The third group was treated with only rHuEPO. Control cells were cultured in the absence of rHuEPO and LPS. Apoptosis was determined by flow cytometric DNA analysis, propidium iodide staining, cellular DNA fragmentation by ELISA, and gel electrophoresis. RESULTS: LPS-treated cells showed an increase in hypodiploid DNA (36.4 +/- 6.1%) compared with controls (9.8 +/- 3.3%, P < 0.001). Preincubation with rHuEPO decreased this effect to 14.7 +/- 5.1% (P < 0.001). Apoptosis determined by propidium iodide was observed in 33 +/- 8% of LPS-treated cells, but in only 9 +/- 3% of cells preincubated with rHuEPO cells (P < 0.001). Similarly, DNA fragmentation was decreased in rHuEPO pretreated cells compared with LPS alone (0.155 OD +/- 0.02 vs. 0.538 +/- 0.09 OD, P < 0.001). DNA breakdown was observed in only LPS-treated cells. CONCLUSIONS: These results suggest that rHuEPO prevents LPS-induced apoptosis in endothelial cells. This protective effect could be an important factor in the action of rHuEPO on vascular endothelium. PMID- 9987079 TI - Recruitment of renal tubular epithelial cells expressing verotoxin-1 (Stx1) receptors in HIV-1 transgenic mice with renal disease. AB - BACKGROUND: Human immunodeficiency virus (HIV)-infected children are at risk of developing several renal parenchymal diseases, including hemolytic uremic syndrome (HUS). HUS is most frequently caused by infection with enteric Escherichia coli producing Shiga-like toxins (Stxs). In vitro studies have shown that cytokines known to be present at high systemic levels in HIV-1-infected children up-regulate the expression of the Stx glycolipid receptor (Gb3) in cultured endothelial cells. Thus, we studied whether HIV-1 or the HIV-associated "cytokine milieu" could modulate the expression of renal Stxs receptors in vivo. METHODS: We used HIV-1 transgenic mice (HIV-Tg) expressing a deletion mutant of HIV-1 (pNL4-3). These mice develop renal disease similar to that of HIV-1 infected children. The expression of Gb3 was studied in renal sections from control and HIV-Tg mice by histochemistry, thin layer chromatography overlay studies, and high-pressure liquid chromatography. RESULTS: By histochemistry, we found a significant recruitment of renal tubular epithelial cells expressing Gb3 in HIV-Tg mice with nephropathy, whereas kidneys from control mice showed limited staining in renal tubules. Gb3 was not found in glomeruli of either control or HIV-Tg mice. Thin layer chromatography overlay studies with Stxs and high pressure liquid chromatography studies confirmed the marked elevation of Gb3 in HIV-Tg kidneys with renal disease. CONCLUSIONS: These results suggest that the presence of HIV-associated nephropathy is associated with the recruitment of renal tubular epithelial cells expressing Stx1 receptors. The up-regulation of Stx1 receptors in HIV-diseased kidneys may increase the sensitivity of these cells to the cytotoxic effects of Stxs. PMID- 9987080 TI - Extracellular matrix regulates apoptosis in human neutrophils. AB - BACKGROUND: During inflammation, polymorphonuclear neutrophils (PMNs) migrate into the affected tissue interacting with extracellular matrix (ECM) proteins. We tested the hypothesis that PMN-matrix interaction affects PMN apoptosis. METHODS: Apoptosis of human PMNs was detected by DNA-fragmentation assay and was quantitated by flow cytometry, ultraviolet and light microscopy. Cell adhesion was assessed by a toluidine blue assay, and cell spreading was detected by phase contrast microscopy. Protein tyrosine phosphorylation was studied using Western blotting and confocal microscopy. RESULTS: PMN apoptosis was not different in unstimulated cultures on either surface-adherent fibronectin or on PolyHema, a surface that prevents cell adherence. However, tumor necrosis factor-alpha (TNF alpha) treatment significantly increased apoptosis on fibronectin (37 +/- 4%) compared with PolyHema (20 +/- 3%). Tests on other matrix substances revealed that the percentage of apoptotic PMNs in the presence of TNF alpha was 8 +/- 1% on PolyHema, 26 +/- 4% on fibronectin, 17 +/- 2% on collagen I, 16 +/- 2% on collagen IV, and 16 +/- 3% on laminin (P < 0.05 for all matrices compared with PolyHema). Preincubation with genistein (50 microM) significantly inhibited TNF alpha-mediated apoptosis on fibronectin (39 +/- 4% to 21 +/- 4%) but not on PolyHema (21 +/- 4% to 16 +/- 4%). Genistein also reduced PMN spreading on fibronectin. In contrast, inhibitors of mitogen-activated protein kinase and protein kinase C showed no effect on PMN apoptosis. Fibronectin strongly increased tyrosine phosphorylation of three 102, 63, and 54 kDa proteins. Five newly tyrosine-phosphorylated 185, 85, 66, 56, and 42 kDa bands were also visible. Using confocal microscopy, highest tyrosine phosphorylation was localized to sites of cell-matrix interaction. CONCLUSIONS: ECM influences apoptosis in TNF alpha-activated, adherent, spreading PMNs. The process is regulated by tyrosine phosphorylation. Acceleration of apoptosis may shorten the PMN lifespan and thereby locally regulate inflammation. PMID- 9987081 TI - Induction of cyclooxygenase-2 in human synovial cells by beta 2-microglobulin. AB - BACKGROUND: Prostaglandins (PGs) are important mediators of inflammation in arthritis. We evaluated the role of the cycloxygenase-2 (COX-2) enzyme, which regulates PG biosynthesis, in osteoarthropathy associated with hemodialysis associated amyloidosis (HAA) by characterizing COX-2 expression in beta 2 microglobulin-treated human synovial cells. METHODS: We examined the effects of beta 2-microglobulin (beta 2m), a major constituent protein of amyloid fibrils in HAA, on the COX-2 protein and mRNA expression in human synovial cells using Western blot and reverse transcriptase-polymerase chain reaction. RESULTS: beta 2m selectively increased the biosynthesis of COX-2 protein and induction of COX-2 mRNA in a dose-dependent manner. Immunoabsorption of beta 2m-containing media by anti-beta 2m-specific antibody abrogated beta 2m-mediated COX-2 expression on synovial cells. On the other hand, dexamethasone markedly suppressed the induction of COX-2 protein and mRNA in beta 2m-stimulated synovial cells. CONCLUSIONS: Our results suggest that induction of COX-2 expression by beta 2m may be an important component of the inflammatory process in hemodialysis associated osteoarthropathy. PMID- 9987082 TI - Increased levels of transforming growth factor-beta in HIV-associated nephropathy. AB - BACKGROUND: Human immunodeficiency virus-associated nephropathy (HIVAN) is a renal disease of unknown pathogenesis. Recent evidence suggests that the fibrogenic cytokine transforming growth factor-beta (TGF-beta) might be involved. We hypothesized that overproduction of TGF-beta in the kidney might be involved in the pathogenesis of HIVAN. METHODS: The mRNA and protein expression of TGF beta isoforms, TGF-beta 1, TGF-beta 2, and TGF beta 3, deposition of matrix proteins induced by TGF-beta, and levels of HIV Tat protein were studied in HIVAN. Controls included normal and diseased kidneys from HIV-positive and negative patients. The ability of Tat to induce production of TGF-beta and matrix proteins was also studied in human mesangial cells. RESULTS: Normal kidneys, thin basement membrane nephropathy, and minimal change disease were negative for the three TGF-beta isoforms and Tat. In HIVAN, levels of TGF-beta isoforms and Tat were significantly increased, along with the expression of TGF-beta mRNA and deposition of matrix proteins stimulated by TGF-beta. Increased levels of TGF beta isoforms, but not Tat, were also found in other glomerular diseases characterized by matrix accumulation. HIV infection, in the absence of HIVAN, was not associated with an increase in TGF-beta or Tat expression. Tat stimulated the expression and production of TGF-beta 1 and matrix proteins by human mesangial cells. CONCLUSIONS: Our findings suggest that overproduction of TGF-beta is involved in the pathogenesis of HIVAN. PMID- 9987083 TI - Cl- channels in basolateral TAL membranes: XIII. Heterogeneity between basolateral MTAL and CTAL Cl- channels. AB - BACKGROUND: Antidiuretic hormone (ADH) or adenosine 3', 5'-cyclic phosphate (cAMP) analogues augment net NaCl absorption in microperfused mouse medullary thick ascending limb (MTAL) segments but not in cortical thick ascending limb (CTAL) segments. This ADH-dependent MTAL effect is due to increased apical Na+/K+/2Cl- admittance and apical K+ recycling accompanied by a rise in calculated intracellular Cl- concentrations and by a threefold rise in basolateral Cl- conductance. rbClC-Ka, a 75.2 member of the ClC family of Cl- channels, mediates net Cl- absorption in the MTAL. The gating characteristics of rbClC-Ka channels from their intracellular surfaces are, to our knowledge, unique among Cl- channels. The channels are activated by small increases in intracellular Cl- (K1/2 = 10 mM Cl-). Adenosine triphosphate plus the catalytic subunit of protein kinase A (ATP + PKA) gate rbClC-Ka when cytosolic Cl- concentrations are 25 mM. Thus, in mouse MTAL segments, ADH-dependent rises in cytosolic Cl- are primarily responsible for basolateral Cl- conductance increases. METHODS: These experiments compared the properties of Cl- channels fused into bilayers from basolaterally enriched vesicles from cultured mouse CTAL cells with rbClC-Ka channels. RESULTS: The key findings were that anti-rbClC-Ka, antibody that recognizes and blocks rbClC-Ka, recognized and blocked basolateral Cl- channels in CTAL cells, that the extracellular faces of the CTAL channels were, like rbClC-Ka, substrate gated with a K1/2 of approximately 170 mM Cl-, and that, unlike rbClC-Ka channels, cytosolic faces of basolateral CTAL Cl- channels were not gated by either increasing cytosolic Cl- concentrations or cytosolic (ATP + PKA). This failure of activation of basolateral CTAL Cl- channels was confirmed using excised patch clamp studies. Finally, on Western blots, anti rbClC-Ka recognized a 74 kDa band on basolateral CTAL vesicles. CONCLUSIONS: Basolateral CTAL Cl- channels probably share a high degree of structural homology and possibly molecular mass with rbClC-Ka channels. However, significant differences between rbClC-Ka channels and CTAL Cl- channels account for the inability of increasing either cytosolic Cl- or (PKA + ATP) to raise Po in CTAL basolateral Cl- channels. PMID- 9987084 TI - Increased dietary oxalate does not increase urinary calcium oxalate saturation in hypercalciuric rats. AB - BACKGROUND: Human calcium oxalate (CaOx) nephrolithiasis may occur if urine is supersaturated with respect to the solid-phase CaOx. In these patients, dietary oxalate is often restricted to reduce its absorption and subsequent excretion in an effort to lower supersaturation and to decrease stone formation. However, dietary oxalate also binds intestinal calcium which lowers calcium absorption and excretion. The effect of increasing dietary oxalate on urinary CaOx supersaturation is difficult to predict. METHODS: To determine the effect of dietary oxalate intake on urinary supersaturation with respect to CaOx and brushite (CaHPO4), we fed 36th and 37th generation genetic hypercalciuric rats a normal Ca diet (1.2% Ca) alone or with sodium oxalate added at 0.5%, 1.0%, or 2.0% for a total of 18 weeks. We measured urinary ion excretion and calculated supersaturation with respect to the CaOx and CaHPO4 solid phases and determined the type of stones formed. RESULTS: Increasing dietary oxalate from 0% to 2.0% significantly increased urinary oxalate and decreased urinary calcium excretion, the latter presumably due to increased dietary oxalate-binding intestinal calcium. Increasing dietary oxalate from 0% to 2.0% decreased CaOx supersaturation due to the decrease in urinary calcium offsetting the increase in urinary oxalate and the decreased CaHPO4 supersaturation. Each rat in each group formed stones. Scanning electron microscopy revealed discrete stones and not nephrocalcinosis. X-ray and electron diffraction and x-ray microanalysis revealed that the stones were composed of calcium and phosphate; there were no CaOx stones. CONCLUSION: Thus, increasing dietary oxalate led to a decrease in CaOx and CaHPO4 supersaturation and did not alter the universal stone formation found in these rats, nor the type of stones formed. These results suggest the necessity for human studies aimed at determining the role, if any, of limiting oxalate intake to prevent recurrence of CaOx nephrolithiasis. PMID- 9987085 TI - Reduced endogenous endothelin-1-mediated vascular tone in chronic renal failure. AB - BACKGROUND: Endothelin-1 generated by the vascular endothelium contributes to basal vascular tone and blood pressure in healthy humans. Plasma concentrations of endothelin-1, which are elevated in chronic renal failure (CRF), may contribute to increased vascular tone. METHODS: We investigated the contribution of endogenous and exogenous endothelin-1 to the maintenance of vascular tone in patients with CRF (creatinine > or = 200 mumol/liter) and in age- and sex-matched healthy subjects. In a series of experiments, we measured forearm vascular responses to intra-arterial norepinephrine (30 to 240 pmol/min), endothelin-1 (5 pmol/min), the selective endothelin A (ETA) receptor antagonist BQ-123 (3 mg/hr), the mixed endothelin-converting enzyme and neutral endopeptidase inhibitor phosphoramidon (30 nmol/min), and the selective neutral endopeptidase inhibitor thiorphan (30 nmol/min). RESULTS: The maximum reduction in forearm blood flow (FBF) to norepinephrine in CRF (33 +/- 7%) was similar to that in controls (43 +/ 7%, P = 0.53). Endothelin-1 also produced a similar reduction in FBF in CRF (35 +/- 6%) and controls (36 +/- 5%, P = 0.81). BQ-123 increased FBF in CRF (11 +/- 4%) but significantly less than in controls (44 +/- 10%, P = 0.02). Phosphoramidon increased FBF in CRF (68 +/- 20%), again significantly less than in controls (181 +/- 41%, P = 0.001). Thiorphan reduced FBF similarly in CRF (22 +/- 6%) and controls (14 +/- 6%, P = 0.39). Responses to phosphoramidon were substantially greater than to BQ-123. CONCLUSIONS: These studies show that endogenous generation of endothelin-1 contributes to the maintenance of resting vascular tone in patients with CRF, as well as in healthy subjects. Although the contribution of endogenous endothelin-1 to resting vascular tone appears to be reduced in CRF, ETA receptor antagonism, and particularly endothelin-converting enzyme inhibition, should be explored as means by which to reduce vascular tone and blood pressure in patients with CRF. PMID- 9987086 TI - Low-protein diet and kidney function in insulin-dependent diabetic patients with diabetic nephropathy. AB - BACKGROUND: Initiation of a low-protein diet (LPD) in patients with various nephropathies induces a faster initial and slower subsequent decline in the glomerular filtration rate (GFR). Whether this initial phenomenon is reversible or irreversible remains to be elucidated. METHODS: We performed an eight-week prospective, randomized, controlled study comparing the effect of an LPD with a normal-protein diet (NPD) in 29 insulin-dependent diabetic patients with diabetic nephropathy. At baseline, the patients were randomized to either an LPD (0.6 g.kg 1.24 hr-1, LPD group, N = 14) or their NPD (NPD group, N = 15) for four weeks (phase I). Between weeks 4 and 8, all patients received their NPD (phase II, recovery). Dietary protein intake (g.kg-1.24 hr-1), GFR (51Cr-EDTA, ml.min-1.1.73 m-2), albuminuria (enzyme-linked immunoadsorbent assay, mg.24 hr-1), and arterial blood pressure (Hawksley random zero sphygmomanometer, mm Hg) were measured at baseline and after four- and eight-weeks of follow-up. During the investigation, all patients in the LPD group (N = 12) and in the NPD group (N = 14) received their usual antihypertensive treatment. RESULTS: At baseline, the LPD group and the NPD group were comparable regarding dietary protein intake, GFR, albuminuria, and arterial blood pressure. During phase I, a significant decline in dietary protein intake, GFR, and albuminuria (mean, 95% CI) was observed in the LPD group [0.4 (0.3 to 0.5) g.kg-1.24 hr-1, 8.6 (3.2 to 13.9) ml.min-1.1.73 m-2, and 28.7 (14.0 to 40.9)%, respectively] compared with the NPD group [0.0 (-0.1 to 0.2) g.kg-1.24 hr-1 (P < 0.0001 between diets), 2.5 (-1.8 to 6.8) ml.min-1.1.73 m-2 (P = 0.07 between diets), and 0.0 (-20.1 to 23.5)% (P < 0.05 between diets), respectively]. Conversely, during phase II, a significant increase in dietary protein intake, GFR, and albuminuria [mean, 95% CI; 0.3 (0.2 to 0.5) g.kg-1.24 hr 1, 5.9 (0.8 to 11.1) ml.min-1.1.73 m-2, and 25.0 (4.5 to 49.6)%, respectively] took place in the LPD group compared with the NPD group [0.0 (-0.2 to 0.1) g.kg 1.24 hr-1 (P < 0.0001 between diets), -2.9 (-6.4 to 0.6) ml.min-1.1.73 m-2 (P < 0.01 between diets), and 2.9 (-18.3 to 29.7)% (P = 0.16 between diets), respectively]. Arterial blood pressure was comparable in the two groups of patients during phase I and II. CONCLUSIONS: Dietary protein restriction for four weeks induces a reversible decline in GFR and albuminuria in insulin-dependent diabetic patients with diabetic nephropathy, whereas systemic blood pressure remains unchanged. PMID- 9987087 TI - Coadministration of albumin and furosemide in patients with the nephrotic syndrome. AB - BACKGROUND: In patients with nephrotic syndrome, the natriuretic effect of furosemide (FU) is diminished. The effect of coadministration of FU and human albumin (HA) has remained controversial. METHODS: In a double-blind, placebo controlled study, nine nephrotic patients (six males, 48 +/- 4 years) on standardized sodium chloride intake, in random order on three separate days, received by intravenous administration for 60 minutes either (a) 60 mg FU plus a sham infusion, (b) 60 mg FU plus 200 ml of a 20% solution of HA, or (c) sham infusion plus 200 ml of a 20% solution of HA. Urinary volume, sodium, albumin and FU excretion, renal hemodynamics, and plasma atrial natriuretic factor concentration were assessed. RESULTS: Administration of FU alone significantly (P < 0.01) increased mean cumulative urinary sodium (259 +/- 30 mmol) and volume excretion (2684 +/- 167 ml) in the first eight hours as compared with the HA infusion alone (118 +/- 12 mmol, 1827 +/- 141 ml). The coadministration of FU and HA caused an even more marked increase (P < 0.01 vs. HA alone) of urinary sodium (312 +/- 28 mmol) and volume excretion (3230 +/- 201 ml); the difference to FU administration alone was significant (P < 0.05). Plasma atrial natriuretic factor, serum albumin concentration, and urinary albumin excretion increased significantly on both HA infusion days, whereas urinary excretion of FU remained unchanged with HA coadministration. Glomerular filtration rate (CIn) was not significantly affected by any of the infusion protocols, but effective renal plasma flow (CPAH) increased significantly on both HA infusion days. CONCLUSIONS: Coadministration of HA potentiates the action of FU in patients with the nephrotic syndrome, but only modestly. This effect is mediated by changes in renal hemodynamics. PMID- 9987088 TI - Imprecision of the hemodialysis dose when measured directly from urea removal. Hemodialysis Study Group. AB - BACKGROUND: The postdialysis blood urea nitrogen (BUN; Ct) is a pivotal parameter for assessing hemodialysis adequacy by conventional blood-side methods, but Ct is relatively unstable because of hemodialysis-induced disequilibrium. The uncertainty associated with this method is potentially reduced or eliminated by measuring urea removed on the dialysate side, a more direct approach that can determine adequacy from the fraction of urea removed and by substituting an estimate of the equilibrated postdialysis BUN (Ceq) for Ct. For a patient with a known urea volume (V), Ceq, the equilibrated Kt/V (eKt/V), and the solute removal index (SRI) can be calculated from the predialysis BUN (C0), total urea nitrogen removed (A), and V from simple mass balance calculations (dialysate/volume method). However, a theoretical error analysis showed that relatively small errors in A, C0, or V are magnified when SRI or eKt/V is calculated using this method, especially at higher eKt/V values (for example, if eKt/V = 1.4 per dialysis, a 7% dialysate collection error causes a 20% error in eKt/V). METHODS: During three to four baseline dialyses in each of 39 patients enrolled in the pilot phase of the HEMO Study, "A" was measured using an instrument that sampled dialysate frequently (Biostat), and V was calculated from A, C0, and Ceq (median CV for V = 5.6%). The mean V was then applied to the dialysate/volume method to estimate eKt/V and SRI during two to five subsequent dialyses per patient (comparison dialyses). The accuracy and precision of these estimates were assessed by comparing them with eKt/V and SRI derived from a direct measurement of Ceq drawn 30 minutes after dialysis (reference method), from mathematical curve-fitting of sequential dialysate urea concentrations (dialysate curve-fit method), and from another blood-side method that estimates eKt/V from single pool Kt/V and the fractional rate of solute removal (rate method): eKt/V = spKt/V - 0.6.K/V + 0.03. RESULTS: During 128 comparison dialyses, median absolute errors for calculated eKt/V compared with the reference method were 0.169, 0.061, and 0.071 for the dialysate/volume method, the rate method, and the dialysate curve fitting method, respectively. The corresponding correlation coefficients were 0.47, 0.88, and 0.81. For SRI, median absolute errors were 0.044, 0.018, and 0.027, and the correlation coefficients were 0.54, 0.85, and 0.74 for the three methods. CONCLUSIONS: The precision of eKt/V and SRI measurements was significantly lower for the dialysate/volume method compared with the blood-side methods. Inclusion of the dialysate curve analysis provided by the Biostat restored precision to the dialysate method to a level comparable to that of the blood-side methods. New techniques employing dialysate urea analysis should include a concentration profile to avoid these inherent methodological errors and assure the accuracy of eKt/V and SRI. PMID- 9987089 TI - Inflammation enhances cardiovascular risk and mortality in hemodialysis patients. AB - BACKGROUND: Atherosclerosis, a major problem in patients on chronic hemodialysis, has been characterized as an inflammatory disease. C-reactive protein (CRP), the prototypical acute phase protein in humans, is a predictor of cardiovascular mortality in the general population. We hypothesize that several of the classic, as well as nontraditional, cardiovascular risk factors may respond to acute phase reactions. An activated acute phase response may influence or predict cardiovascular risk. METHODS: In 280 stable hemodialysis patients, serum lipids, apolipoproteins (apo) A-I and B, lipoprotein(a) [Lp(a)], fibrinogen, and serum albumin (Salb) were determined in relation to CRP and serum amyloid A (SAA), two sensitive markers of an acute phase response. Mortality was monitored prospectively over a two year period. RESULTS: Serum CRP and SAA were found to be elevated (more than 8 and more than 10 mg/liter, respectively) in 46% and 47% of the patients in the absence of clinically apparent infection. Patients with elevated CRP or SAA had significantly higher serum levels of Lp(a), higher plasma fibrinogen, and lower serum levels of high-density lipoprotein cholesterol, apo A I, and Salb than patients with normal CRP or SAA. The rise in Lp(a) concentration was restricted to patients exhibiting high molecular weight apo(a) isoforms. During follow-up, 72 patients (25.7%) had died, mostly due to cardiovascular events (58%). Overall mortality and cardiovascular mortality were significantly higher in patients with elevated CRP (31% vs. 16%, P < 0.0001, and 23% vs. 5%, P < 0.0001, respectively) or SAA (29% vs. 19%, P = 0.004, and 20 vs. 10%, P = 0.008, respectively) and were also higher in patients with Salb of lower than 40 g/liter (44% vs. 14%, P < 0.0001, and 34% vs. 6%, P < 0.0001, respectively). Univariate Cox regression analysis demonstrated that age, diabetes, pre-existing cardiovascular disease, body mass index, CRP, SAA, Salb, fibrinogen, apo A-I, and Lp(a) were significantly associated with the risk of all-cause and cardiovascular mortality. During multivariate regression analysis, SAA, fibrinogen, apo A-I, and Lp(a) lost their predictive values, but age and CRP remained powerful independent predictors of both overall death and cardiovascular death. CONCLUSION: These results suggest that a considerable number of hemodialysis patients exhibit an activated acute phase response, which is closely related to high levels of atherogenic vascular risk factors and cardiovascular death. The mechanisms of activated acute phase reaction in patients on chronic hemodialysis remain to be identified. A successful treatment of the inflammatory condition may improve long term survival in these patients. PMID- 9987090 TI - Increased susceptibility to erythrocyte C5b-9 deposition and complement-mediated lysis in chronic renal failure. AB - BACKGROUND: Decreased red blood cell survival contributes to the anemia of chronic renal failure patients. Because patients on chronic dialysis therapy are frequently exposed to excessive complement activation, we investigated the susceptibility of this patient population to erythrocyte C5b-9 deposition, complement-mediated lysis, and ghost formation. METHODS: We developed a flow cytometric assay using antibodies to both glycophorin and the C5b-9 complex to detect C5b-9 deposition on intact erythrocytes and erythrocyte ghosts. Serum C5b 9 levels and C5b-9 deposition on erythrocyte ghosts were measured by enzyme linked immunosorbent assay. RESULTS: A significant increase in C5b-9 deposition on intact erythrocytes was demonstrated in patients with advanced chronic renal failure (2.2 +/- 0.5%) and in patients on chronic maintenance hemodialysis (2.3 +/- 0.4%) compared with normal volunteers (0.9 +/- 0.1%, P = 0.005 vs. chronic renal failure, P < 0.001 vs. chronic hemodialysis patients). There was also a significantly higher percentage of C5b-9-positive erythrocyte ghosts in patients with advanced chronic renal failure (20.6 +/- 5%) and in chronic hemodialysis patients (15.5 +/- 3.1%) compared with normal controls (2.6 +/- 0.9%, P < or = 0.001 vs. advanced chronic renal failure and chronic hemodialysis patients). Treatment of erythrocyte preparations with cobra venom factor, which activates the complement cascade, resulted in dramatic increases in the percentages of C5b 9-positive erythrocyte ghosts in patients with chronic renal failure (49.9 +/- 6.9%) and in chronic hemodialysis patients (45.0 +/- 4.2%) compared with normal volunteers (22.3 +/- 2.7%, P < 0.001 vs. chronic renal failure and chronic hemodialysis patients). Erythrocyte membrane expression of the complement regulatory proteins CD59 and CD55 did not significantly differ between normal controls and hemodialysis patients. Plasma C5b-9 levels after cobra venom factor stimulation were higher in chronic renal failure patients (538 micrograms/ml) compared with normal controls (345 micrograms/ml, P < 0.001). CONCLUSIONS: Patients with chronic renal failure and on hemodialysis therapy are susceptible to erythrocyte C5b-9 deposition with subsequent lysis and ghost formation. Susceptibility to complement-mediated erythrocyte injury may contribute to the anemia of chronic renal disease. PMID- 9987091 TI - Hyaluronan decreases peritoneal fluid absorption: effect of molecular weight and concentration of hyaluronan. AB - BACKGROUND: We have recently shown that the addition of hyaluronan to peritoneal dialysis solution could decrease the peritoneal fluid absorption rate, possibly through decreasing peritoneal tissue hydraulic conductivity. The physical chemical properties of hyaluronan were found to be both molecular weight and concentration dependent. In this study, we investigated the effects of different molecular weight as well as different concentrations of hyaluronan on the peritoneal fluid kinetics. METHODS: A four-hour dwell study was performed in 48 male Sprague-Dawley rats (6 rats in each group) with 131I albumin (RISA) as an intraperitoneal volume marker. Each rat was intraperitoneally injected with 25 ml of 1.36% glucose dialysate alone (control) or with 0.01% hyaluronan (HA) with different molecular weights [85,000 (HA85K group), 280,000 (HA280K group), 500,000 (HA500K group), and 4,000,000 (HA4M group) molecular wt] or with a different concentrations of hyaluronan [(molecular wt 500,000); 0.01% (0.01% HA group), 0.05% (0.05% HA group), 0.1% (0.1% HA group), and 0.5% (0.5% HA group) hyaluronan]. RESULTS: The peritoneal fluid absorption rate (as assessed by the RISA elimination rate, KE) was significantly decreased in the HA500K and H4M groups as well as in all the different concentration groups (with molecular wt 500,000) as compared with the control group, resulting in significantly higher net fluid removal in these groups (except for the H4M group) as compared with the control group. In the 0.5% HA group (but not in the other hyaluronan groups), the direct lymphatic absorption (KEB) was also significantly decreased. The transcapillary ultrafiltration rate (Qu) was significantly lower in the HA4M group as compared with the control group but significantly higher in the 0.05% HA (and tended to be higher in the 0.1% HA group) as compared with the other groups. No difference in Qu was found between the 0.5% HA group as compared with the control group, despite a more marked decrease in KE in this group as compared with the H4M group. There were no significant differences in KE, Qu, and net fluid removal between the HA85K and HA280K groups and the control group. CONCLUSIONS: Our results suggest that (a) the addition of hyaluronan to dialysate could decrease peritoneal fluid absorption and thus increase the net ultrafiltration; this effect appears to be both size dependent and concentration dependent. (b) High molecular weight fraction of hyaluronan may also decrease the transcapillary Qu by decreasing tissue hydraulic conductivity. (c) A higher concentration of hyaluronan in dialysate resulted in a more marked decrease in peritoneal fluid absorption (absorption to peritoneal tissues as well as direct lymphatic absorption), possibly through both decreasing tissue hydraulic conductivity and increasing fluid viscosity. (d) Decreasing tissue hydraulic conductivity by adding a high concentration of hyaluronan to dialysate does not decrease the transcapillary ultrafiltration, possibly because the osmotic effect of hyaluronan may counterbalance the decrease in transcapillary ultrafiltration because of the decrease in tissue hydraulic conductivity. PMID- 9987092 TI - Nature and mediators of renal lesions in kidney transplant patients given cyclosporine for more than one year. AB - BACKGROUND: Cyclosporine (CSA) has improved patients and organ-graft survival rates, but its chronic nephrotoxicity is still an issue. Although prolonged vasoconstriction could contribute to chronic CsA tubulointerstitial changes by producing chronic ischemia, this relationship has been difficult to demonstrate thus far, and cellular origin and mediators of these structural alterations remain ill-defined. METHODS: As a part of a clinical trial in kidney transplant recipients on triple immunosuppressive therapy (CsA, azathioprine and steroid), which includes renal biopsy as "per protocol," 22 patients enrolled between 12 and 24 months posttransplantation underwent renal hemodynamic evaluation by measuring glomerular filtration rate and renal plasma flow by the plasma clearance of unlabeled iohexol and the renal clearance of para-aminohippuric acid, respectively. In parallel, the CsA pharmacokinetic profile was also determined. A week later, a protocol biopsy of kidney graft was performed. Light microscopy examination and localization of endothelin-1, RANTES, monocyte chemoattractant protein-1 gene expression by in situ hybridization in the graft specimens were evaluated and related to the pattern of histologic lesions. RESULTS: Ten out of 22 kidney transplant recipients who underwent the protocol biopsy had CsA nephrotoxicity, eight had chronic rejection, and four had no lesions at histological examination. The total daily exposure to CsA was higher in patients with CsA nephrotoxicity than in those with chronic rejection or no lesions at biopsy. Renal function was preserved in the CsA toxicity group as compared with the chronic rejection group, despite some degree of renal hypoperfusion. Tubular atrophy and striped interstitial fibrosis were found in all patients with light microscopical evidence of CsA nephrotoxicity, whereas glomerular and arteriolar lesions were less frequent. Intense staining for endothelin-1, RANTES, and monocyte chemoattractant protein-1 mRNAs selectively localized at tubular epithelial cells was found in biopsies taken from patients with CsA nephrotoxicity, but not in the chronic graft rejection group, whose tubuli had only minimal staining for RANTES mRNA on a few occasions. CONCLUSION: Long-term CsA administration to kidney allograft recipients leads to tubulointerstitial injury independently of its vascular effect. The possible contribution to the development of interstitial fibrosis of inflammatory and growth factors released by tubular cells in which CsA accumulates is proposed. PMID- 9987093 TI - Effects of sodium nitroprusside on hemodialysis-induced platelet activation. AB - BACKGROUND: Hemodialysis (HD) is associated with increased platelet activation as reflected by enhanced P-selectin expression on platelets and by increased formation of heterotypic platelet-leukocyte aggregates. Both may play a pathophysiologic role in HD-associated platelet dysfunction or the propagation of atherosclerosis. As nitric oxide (NO) is a potent inhibitor of platelet activation, we were interested in whether HD-induced platelet activation could be blunted by a NO donor. METHODS: After a pilot study in 12 patients to gain an estimate for the sample size, the main trial was conducted as a randomized, double-blind, placebo-controlled, two-way, cross-over study. Twelve patients received an infusion of sodium nitroprusside (1 microgram/kg/min for over 15 min) or placebo into the inlet port of the HD device. RESULTS: Platelet activation increased within five minutes after start of HD (P < 0.05). Infusion of sodium nitroprusside neither decreased platelet activation (P-selectin + platelets) nor affected the number of platelet-leukocyte aggregates (CD41+ neutrophils) as measured by flow cytometry. CONCLUSION: Although NO may have inhibitory effects on platelet activation in vivo, our results confirm recent findings showing that NO donors were ineffective in preventing platelet activation by extracorporeal circulation during cardiopulmonary bypass or plateletpheresis. Thus, NO donors do not appear to be ideal candidate drugs to inhibit HD-associated platelet activation. PMID- 9987094 TI - Early graft function and patient survival following cadaveric renal transplantation. AB - BACKGROUND: The influence of events that occur early following renal transplantation such as delayed graft function (DGF) and acute rejection on long term graft survival has been widely reported, but its association with patient survival has received less attention. METHODS: We studied 589 patients who received their first cadaveric transplants between 1984 and 1993, all of whom received cyclosporine-based immunosuppression and who had a median follow-up of seven years. The following factors were identified, and both univariate and multivariate analyses were used to determine their association with long-term patient and graft survival: age, sex, duration of pretransplant dialysis, primary renal disease, immediate graft function (IGF), DGF, primary nonfunction (PNF), acute rejection, and serum creatinine at 3, 6, and 12 months. RESULTS: Patients with PNF had a poorer survival than those with DGF and IGF (P = 0.01), but there was no difference in survival between DGF and IGF (P = 0.54). Good graft function (serum creatinine of less than 200 mumol/liter) at three months was predictive of better long-term patient survival (P = 0.03). Other factors associated with poor patient outcome were older age, diabetes, adult polycystic kidney disease, male gender, and acute rejection. Cardiovascular disease was the most common cause of death (51.8%). Good graft function at three months (P < 0.001) and an absence of rejection episodes (P = 0.01) were associated with better graft survival. CONCLUSION: Patients with poor levels of early graft function (but not DGF) and those with either acute rejection episodes or early graft loss are at an increased risk of early death. These high-risk groups should be targeted for interventional studies in an attempt to improve patient survival. PMID- 9987095 TI - Report of the annual statistical survey of the Japanese Society for Dialysis Therapy in 1996. AB - BACKGROUND: Nearly 170,000 patients were treated by maintenance renal replacement therapy (RRT) in Japan in 1996. The current status of Japanese patients on RRT might, in some way, be suggestive for patients on RRT in other countries. METHODS: The Japanese Society for Dialysis Therapy conducts a questionnaire survey of virtually every dialysis facility in Japan at the end of each year. Here we present the results of our survey of patients undergoing RRT as of the end of 1996, as well as five-year trends (1992-1996) in some of the data. RESULTS: The response rate was 99.8%. At the end of 1996, there were 167,192 patients on maintenance RRT in Japan (1,328 persons per million population). The numbers of patients on maintenance RRT continued to increase during the five-year period. The gross mortality rate for that period ranged from 9.4% to 9.7%. Cuprammonium rayon was the most commonly used material (24.0%) for dialyzer membranes, followed by cellulose triacetate (18.7%). Approximately 5.0% of hemodialysis (HD) patients had a prior history of surgical release of carpal tunnel. The longer the years on HD therapy, the greater the proportion of patients with a history of such an operation. The predialysis plasma beta 2 microglobulin concentration was highest in patients aged 30 to 45 years and declined slightly after the age of 45. There was no significant difference in the HbA1c level between continuous ambulatory peritoneal dialysis and HD patients, both in whom diabetes was the disease causing renal failure. Moreover, among HD patients with diabetes, there was a clear tendency for the HbA1c level to be higher when the normalized protein catabolic rate was higher. CONCLUSION: This report summarizes the latest results of the survey on Japanese patients on RRT. PMID- 9987096 TI - The Banff 97 working classification of renal allograft pathology. AB - BACKGROUND: Standardization of renal allograft biopsy interpretation is necessary to guide therapy and to establish an objective end point for clinical trials. This manuscript describes a classification, Banff 97, developed by investigators using the Banff Schema and the Collaborative Clinical Trials in Transplantation (CCTT) modification for diagnosis of renal allograft pathology. METHODS: Banff 97 grew from an international consensus discussion begun at Banff and continued via the Internet. This schema developed from (a) analysis of data using the Banff classification, (b) publication of and experience with the CCTT modification, (c) international conferences, and (d) data from recent studies on impact of vasculitis on transplant outcome. RESULTS: Semiquantitative lesion scoring continues to focus on tubulitis and arteritis but includes a minimum threshold for interstitial inflammation. Banff 97 defines "types" of acute/active rejection. Type I is tubulointerstitial rejection without arteritis. Type II is vascular rejection with intimal arteritis, and type III is severe rejection with transmural arterial changes. Biopsies with only mild inflammation are graded as "borderline/suspicious for rejection." Chronic/sclerosing allograft changes are graded based on severity of tubular atrophy and interstitial fibrosis. Antibody mediated rejection, hyperacute or accelerated acute in presentation, is also categorized, as are other significant allograft findings. CONCLUSIONS: The Banff 97 working classification refines earlier schemas and represents input from two classifications most widely used in clinical rejection trials and in clinical practice worldwide. Major changes include the following: rejection with vasculitis is separated from tubulointerstitial rejection; severe rejection requires transmural changes in arteries; "borderline" rejection can only be interpreted in a clinical context; antibody-mediated rejection is further defined, and lesion scoring focuses on most severely involved structures. Criteria for specimen adequacy have also been modified. Banff 97 represents a significant refinement of allograft assessment, developed via international consensus discussions. PMID- 9987097 TI - The ethics of organ transplantation reconsidered: paid organ donation and the use of executed prisoners as donors. AB - We examine the arguments for and against the practice of paid organ donation and the use of judicially executed prisoners as seen in a world context. Although Western opinion is almost universally against both practices, we seek to establish that this has arisen largely from justification of an initial revulsion against both and not from reasoned ethical debate. In examining the most commonly cited arguments against these practices, we demonstrate that this revulsion arises mainly from the abuses to which both processes have been subjected, rather than the acts themselves, together with opposition to a death penalty. At the moment and for some future time, in the absence or shortage of dialysis in large parts of the developing world, transplanted organs represent the only means of treating end-stage renal failure. Thus, a clear ethical conflict arises as to whether greater harm or good is done by allowing individuals to die or adopting strategies for obtaining organs that raise ethical problems. We call for continued reasoned ethical debate on both issues, rather than accepting that the argument is already over. PMID- 9987098 TI - Ethics of paid organ donation and the use of executed prisoners as donors: a dialectic with professors Cameron and Hoffenberg. PMID- 9987099 TI - COX2 selective NSAIDs and renal function: gain without pain? PMID- 9987100 TI - Toward an effective gene therapy in renal disease. PMID- 9987101 TI - Prevention of restenosis of central venous stricture after percutaneous transluminal angioplasty and endovascular stenting by brachytherapy. PMID- 9987102 TI - Long-term analgesic use and renal disease. PMID- 9987103 TI - Insulin-like growth factor I in essential hypertension. PMID- 9987104 TI - Negative regulation of bacterial heat shock genes. AB - The expression of eubacterial heat shock genes is efficiently controlled at the transcriptional level by both positive and negative mechanisms. Positive control operates by the use of alternative sigma factors that target RNA polymerase to heat shock gene promoters. Alternatively, bacteria apply repressor-dependent mechanisms, in which transcription of heat shock genes is initiated from a classical housekeeping promoter and cis-acting DNA elements are used in concert with a cognate repressor protein to limit transcription under physiological conditions. Eight examples of negative regulation will be presented, among them the widespread CIRCE/HrcA system and the control by HspR in Streptomyces. Both mechanisms are designed to permit simple feedback control at the level of gene expression. Many bacteria have established sophisticated regulatory networks, often combining positive and negative mechanisms, in order to allow fine-tuned heat shock gene expression in an environmentally responsive way. PMID- 9987105 TI - Germination of Bacillus anthracis spores within alveolar macrophages. AB - The fatal character of the infection caused by inhalation of Bacillus anthracis spores results from a complex pathogenic cycle involving the synthesis of toxins by the bacterium. We have shown using immunofluorescent staining, confocal scanning laser microscopy and image cytometry analysis that the alveolar macrophage was the primary site of B. anthracis germination in a murine inhalation infection model. Bacillus anthracis germinated inside murine macrophage-like RAW264.7 cells and murine alveolar macrophages. Germination occurred in vesicles derived from the phagosomal compartment. We have also demonstrated that the toxin genes and their trans-activator, AtxA, were expressed within the macrophages after germination. PMID- 9987106 TI - The long-term cytoskeletal rearrangement induced by rabbit enteropathogenic Escherichia coli is Esp dependent but intimin independent. AB - Attaching and effacing rabbit enteropathogenic Escherichia coli (REPEC) of the O103 serogroup adhere diffusely on HeLa cells and trigger a slow progressive cytopathic effect (CPE) characterized by the recruitment of vinculin and the assembly of actin stress fibres. In contrast to REPEC O103, the reference human EPEC strain E2348/69 is unable to trigger the CPE. In this study, we have shown first that the fimbrial adhesin AF/R2, which mediates the diffuse adhesion of REPEC O103, was not sufficient to induce the CPE capability upon E2348/69. Non polar mutants of REPEC O103 for espA, espB, espD and eae were then constructed. The four mutants were unable to induce attaching and effacing lesions in the rabbit ileal loop model. The esp mutants were no longer able to induce the CPE, whereas the eae mutant still induced the CPE. Each espA, -B, -D mutant could be fully complemented in trans by the corresponding cloned esp genes from both the parental strain and the CPE-negative E2348/69 strain, indicating that no single esp encodes the information needed to confer the CPE phenotype. In conclusion, the CPE is the first example of an Esp-dependent but Eae (intimin)-independent alteration of the host cell cytoskeleton by certain EPEC strains. PMID- 9987107 TI - Emergence of recombinant strains of Helicobacter pylori during human infection. AB - Genetic recombination can be important evolutionarily in speeding the adaptation of organisms to new environments and in purging deleterious mutations. Here, we describe polymerase chain reaction (PCR), hybridization and DNA sequence-based evidence of six such exchanges between two strains of Helicobacter pylori during natural mixed infection of a patient in Lithuania. One parent strain contained the 37 kb long, virulence-associated cag pathogenicity island (PAI), and the other strain lacked this PAI. Most H. pylori from the patient had descended from the cag+ parent, but had become cag- during infection. This had resulted from transfer of DNA containing the 'empty site' allele from the cag- strain and homologous recombination, not from excision of the cag PAI without DNA transfer. Other cases of recombination involved genes for an outer membrane protein (omp5 and omp29; also called HP0227 and HP1342) and a putative phosphoenolpyruvate synthase (ppsA; HP0121). Replacement of a short patch of DNA sequence (36-124 bp) was also seen. As the chance of forming any given recombinant is small, the abundance of recombinants in this patient suggests selection for particular recombinant genotypes during years of chronic infection. We suggest that genetic exchange among unrelated H. pylori strains, as documented here, is important because of the diversity of this gastric pathogen and its human hosts. Certain H. pylori recombinants may grow better in a given host than either parent. The vigour of growth, in turn, could impact on the severity of disease that infection can elicit. PMID- 9987108 TI - Type III secretion by Salmonella typhimurium does not require contact with a eukaryotic host. AB - The type III secretion system encoded by pathogenicity island I in Salmonella typhimurium delivers proteins to the external milieu and into the eukaryotic host cell. The principal factor in induction of the secretion system was found to be a change in the pH of the culture medium from acidic to mildly alkaline. The synthesis of components of the secretion machinery and the production and secretion of substrates occur simultaneously and do not require contact with a eukaryotic host cell. This argues against the concept that type III secretion in S. typhimurium is a process in which the delivery of a presynthesized pool of substrates is triggered by contact with a eukaryotic host cell. PMID- 9987109 TI - Novel ribosomal mutations affecting translational accuracy, antibiotic resistance and virulence of Salmonella typhimurium. AB - Many mutations in rpsL cause resistance to, or dependence on, streptomycin and are restrictive (hyperaccurate) in translation. Dependence on streptomycin and hyperaccuracy can each be reversed phenotypically by mutations in either rpsD or rpsE. Such compensatory mutations have been shown to have a ram phenotype (ribosomal ambiguity), increasing the level of translational errors. We have shown recently that restrictive rpsL alleles are also associated with a loss of virulence in Salmonella typhimurium. To test whether ram mutants could reverse this loss of virulence, we have isolated a set of rpsD alleles in Salmonella typhimurium. We found that the rpsD alleles restore the virulence of strains carrying restrictive rpsL alleles to a level close to that of the wild type. Unexpectedly, three out of seven mutant rpsD alleles tested have phenotypes typical of restrictive alleles of rpsL, being resistant to streptomycin and restrictive (hyperaccurate) in translation. These phenotypes have not been previously associated with the ribosomal protein S4. Furthermore, all seven rpsD alleles (four ram and three restrictive) can phenotypically reverse the hyperaccuracy associated with restrictive alleles of rpsL. This is the first demonstration that such compensations do not require that the compensating rpsD allele has a ribosomal ambiguity (ram) phenotype. PMID- 9987110 TI - The hprK gene of Enterococcus faecalis encodes a novel bifunctional enzyme: the HPr kinase/phosphatase. AB - The HPr kinase of Gram-positive bacteria is an ATP-dependent serine protein kinase, which phosphorylates the HPr protein of the bacterial phosphotransferase system (PTS) and is involved in the regulation of carbohydrate metabolism. The hprK gene from Enterococcus faecalis was cloned via polymerase chain reaction (PCR) and sequenced. The deduced amino acid sequence was confirmed by microscale Edman degradation and mass spectrometry combined with collision-induced dissociation of tryptic peptides derived from the HPr kinase of E. faecalis. The gene was overexpressed in Escherichia coli, which does not contain any ATP dependent HPr kinase or phosphatase activity. The homogeneous recombinant protein exhibits the expected HPr kinase activity as well as a P-Ser-HPr phosphatase activity, which was assumed to be a separate enzyme activity. The bifunctional HPr kinase/phosphatase acts preferentially as a kinase at high ATP levels of 2 mM occurring in glucose-metabolizing Streptococci. At low ATP levels, the enzyme hydrolyses P-Ser-HPr. In addition, high concentrations of phosphate present under starvation conditions inhibit the HPr kinase activity. Thus, a putative function of the enzyme may be to adjust the ratio of HPr and P-Ser-HPr according to the metabolic state of the cell; P-Ser-HPr is involved in carbon catabolite repression and regulates sugar uptake via the phosphotransferase system (PTS). Reinvestigation of the previously described Bacillus subtilis HPr kinase revealed that it also possesses P-Ser-HPr phosphatase activity. However, contrary to the E. faecalis enzyme, ATP alone was not sufficient to switch the phosphatase activity of the B. subtilis enzyme to the kinase activity. A change in activity of the B. subtilis HPr kinase was only observed when fructose-1,6-bisphosphate was also present. PMID- 9987111 TI - Translation initiation factor 3 antagonizes authentic start codon selection on leaderless mRNAs. AB - In this study, we have examined the influence of initiation factors on translation initiation of leaderless mRNAs whose 5'-terminal residues are the A of the AUG initiating codon. A 1:1 ratio of initiation factors to ribosomes abolished ternary complex formation at the authentic start codon of different leaderless mRNAs. Supporting this observation, in vitro translation assays using limiting ribosome concentrations with competing leaderless lambda cl and Escherichia coli ompA mRNAs, the latter containing a canonical ribosome binding site, revealed reduced cl synthesis relative to OmpA in the presence of added initiation factors. Using in vitro toeprinting and in vitro translation assays, we show that this effect can be attributed to IF3. Moreover, in vivo studies revealed that the translational efficiency of a leaderless reporter gene is decreased with increased IF3 levels. These studies are corroborated by the observed increased translational efficiency of a leaderless reporter construct in an infC mutant strain unable to discriminate against non-standard start codons. These results suggest that, in the absence of a leader or a Shine-Dalgarno sequence, the function(s) of IF3 limits stable 30S ternary complex formation. PMID- 9987112 TI - ClpP participates in the degradation of misfolded protein in Lactococcus lactis. AB - ClpP proteins constitute a family of homologous proteins found in both prokaryotic and eukaryotic organisms. In Escherichia coli, ClpP is the proteolytic component of a large complex also containing either the ClpA or the ClpX ATPases. We show here that the clpP gene from the Gram-positive bacterium Lactococcus lactis encodes a 22-kDa protein that is induced by low pH and by the t-RNA analogue puromycin, which interferes with translation, resulting in the production of misfolded puromycyl-containing peptides. Northern blot and primer extension analysis showed that clpP expression is also induced by heat shock and that stress induction occurs at the transcriptional level independent of the CIRCE regulatory element often implicated in stress regulation in Gram-positive bacteria. When we disrupted the L. lactis clpP gene by insertional inactivation, the resulting mutant was more sensitive to both heat and puromycin than wild-type cells. Furthermore, cells lacking ClpP had a reduced ability to degrade puromycyl containing peptides, and they synthesized heat shock proteins constitutively in the absence of stress. Thus, our data suggest that ClpP plays a major role in the degradation of misfolded proteins. PMID- 9987113 TI - When drug inactivation renders the target irrelevant to antibiotic resistance: a case story with beta-lactams. AB - By challenging the efficiency of some of our most useful antimicrobial weapons, bacterial antibiotic resistance is becoming an increasingly worrying clinical problem. A good antibiotic is expected to exhibit a high affinity for its target and to reach it rapidly, while escaping chemical modification by inactivating enzymes and elimination by efflux mechanisms. A study of the behaviour of a beta lactamase-overproducing mutant of Enterobacter cloacae in the presence of several penicillins and cephalosporins showed that the minimum inhibitory concentration (MIC) values for several compounds were practically independent of the sensitivity of the target penicillin binding protein (PBP), even for poor beta lactamase substrates. This apparent paradox was explained by analysing the equation that relates the antibiotic concentration in the periplasm to that in the external medium. Indeed, under conditions that are encountered frequently in clinical isolates, the factor characterizing the PBP sensitivity became negligible. The conclusions can be extended to all antibiotics that are sensitive to enzymatic inactivation and efflux mechanisms and must overcome permeability barriers. It would be a grave mistake to neglect these considerations in the design of future antibacterial chemotherapeutic agents. PMID- 9987114 TI - Msn1p/Mss10p, Mss11p and Muc1p/Flo11p are part of a signal transduction pathway downstream of Mep2p regulating invasive growth and pseudohyphal differentiation in Saccharomyces cerevisiae. AB - In Saccharomyces cerevisiae, a network of signal transduction pathways governs the switch from yeast-type growth to pseudohyphal and invasive growth that occurs in response to nutrient limitation. Important elements of this network have been identified, including nutrient signal receptors, GTP-binding proteins, components of the pheromone-dependent MAP kinase cascade and several transcription factors. However, the structural and functional mapping of these pathways is far from complete. Here, we present data regarding three genes, MSN1/MSS10, MSS11 and MUC1/FLO11, which form an essential part of the signal transduction network establishing invasive growth. Both MSN1 and MSS11 are involved in the co regulation of starch degradation and invasive growth. Msn1p and Mss11p act downstream of Mep2p and Ras2p and regulate the transcription of both STA2 and MUC1. We show that MUC1 mediates the effect of Msn1p and Mss11p on invasive growth. In addition, our results suggest that the activity of Msn1p is independent of the invasive growth MAP kinase cascade, but the Mss11p is required for the activation of pseudohyphal and invasive growth by Ste12p. We also show that starch metabolism in S. cerevisiae is subject to regulation by components of the MAP kinase cascade. PMID- 9987115 TI - CtsR, a novel regulator of stress and heat shock response, controls clp and molecular chaperone gene expression in gram-positive bacteria. AB - clpP and clpC of Bacillus subtillis encode subunits of the Clp ATP-dependent protease and are required for stress survival, including growth at high temperature. They play essential roles in stationary phase adaptive responses such as the competence and sporulation developmental pathways, and belong to the so-called class III group of heat shock genes, whose mode of regulation is unknown and whose expression is induced by heat shock or general stress conditions. The product of ctsR, the first gene of the clpC operon, has now been shown to act as a repressor of both clpP and clpC, as well as clpE, which encodes a novel member of the Hsp100 Clp ATPase family. The CtsR protein was purified and shown to bind specifically to the promoter regions of all three clp genes. Random mutagenesis, DNasel footprinting and DNA sequence deletions and comparisons were used to define a consensus CtsR recognition sequence as a directly repeated heptad upstream from the three clp genes. This target sequence was also found upstream from clp and other heat shock genes of several Gram-positive bacteria, including Listeria monocytogenes, Streptococcus salivarius, S. pneumoniae, S. pyogenes, S. thermophilus, Enterococcus faecalis, Staphylococcus aureus, Leuconostoc oenos, Lactobacillus sake, Lactococcus lactis and Clostridium acetobutylicum. CtsR homologues were also identified in several of these bacteria, indicating that heat shock regulation by CtsR is highly conserved in Gram-positive bacteria. PMID- 9987116 TI - Transient transcriptional activation of the Incl1 plasmid anti-restriction gene (ardA) and SOS inhibition gene (psiB) early in conjugating recipient bacteria. AB - The ardA gene of the enterobacterial plasmid CollbP-9 acts to alleviate restriction of DNA by type I systems, while psiB inhibits induction of the bacterial SOS response. Both genes are transferred early in a round of bacterial conjugation as part of the plasmid leading region. We report here that ardA and psiB are transcribed transiently after their conjugative transport into the recipient cell. Transcript levels, monitored by competitive reverse transcription polymerase chain reaction (RT-PCR) amplification of RNA templates, started to increase about 5 min after the initiation of conjugation in a cell population and probably before the first round of plasmid transfer was completed. Genetic evidence is given that the expression of ardA and psiB is activated when the genes enter the recipient cell on the transferring plasmid strand. It is proposed that these and other leading region genes function to promote the establishment of the immigrant plasmid in the new host and are expressed by transcription from promoters active only in single-stranded DNA. PMID- 9987117 TI - Role of SycD, the chaperone of the Yersinia Yop translocators YopB and YopD. AB - Extracellular Yersinia adhering at the surface of a eukaryotic cell translocate effector Yops across the plasma membrane of the cell by a mechanism requiring YopD and YopB, the latter probably mediating pore formation. We studied the role of SycD, the intrabacterial chaperone of YopD. By producing GST-YopB hybrid proteins and SycD in Escherichia coli, we observed that SycD also binds specifically to YopB and that this binding reduces the toxicity of GST-YopB in E. coli. By analysis of a series of truncated GST-YopB proteins, we observed that SycD does not bind to a discrete segment of YopB. Using the same approach, we observed that YopD can also bind to YopB. Binding between YopB and YopD occurred even in the presence of SycD, and a complex composed of these three proteins could be immunoprecipitated from the cytoplasm of Yersinia. In a sycD mutant, the intracellular pool of YopB and YopD was greatly reduced unless the lcrV gene was also deleted. As LcrV is known to interact with YopB and YopD and to promote their secretion, we speculate that SycD prevents a premature association between YopB-YopD and LcrV. PMID- 9987118 TI - On the mechanism of FtsH-dependent degradation of the sigma 32 transcriptional regulator of Escherichia coli and the role of the Dnak chaperone machine. AB - The Escherichia coli sigma 32 transcriptional regulator has been shown to be degraded both in vivo and in vitro by the FtsH (HflB) protease, a member of the AAA protein family. In our attempts to study this process in detail, we found that two sigma 32 mutants lacking 15-20 C-terminal amino acids had substantially increased half-lives in vivo or in vitro, compared with wild-type sigma 32. A truncated version of sigma 32, sigma 32 C delta, was purified to homogeneity and shown to be resistant to FtsH-dependent degradation in vitro, suggesting that FtsH initiates sigma 32 degradation from its extreme C-terminal region. Purified sigma 32 C delta interacted with the DnaK and DnaJ chaperone proteins in a fashion similar to that of wild-type sigma 32. However, in contrast to wild-type sigma 32, sigma 32 C delta was largely deficient in its in vivo and in vitro interaction with core RNA polymerase. As a consequence, the truncated sigma 32 protein was completely non-functional in vivo, even when overproduced. Furthermore, it is shown that wild-type sigma 32 is protected from degradation by FtsH when complexed to the RNA polymerase core, but sensitive to proteolysis when in complex with the DnaK chaperone machine. Our results are in agreement with the proposal that the capacity of the DnaK chaperone machine to autoregulate its own synthesis negatively is simply the result of its ability to sequester sigma 32 from RNA polymerase, thus making it accessible to degradation by the FtsH protease. PMID- 9987119 TI - Hemi-methylated oriC DNA binding activity found in non-specific acid phosphatase. AB - The lacZ-hobH fusion clone, containing an Escherichia coli DNA segment located at 92 min on the chromosomal map, was screened as a producer of E. coli oriC hemi methylated binding activity. We have purified the protein encoded by this locus to near homogeneity. The protein corresponds to the monomeric form of a non specific acid phosphatase (NAP) whose gene has been designated aphA. oriC DNA footprinting experiments showed protection of hemi-methylated probe by partially purified NAP, but not by purified preparations. Yet, gel retardation experiments with an oriC oligonucleotide demonstrated DNA binding activity of purified NAP in the presence of Mg2+. This experiment also showed an increased affinity of the protein for the hemi-methylated probe compared with the fully or unmethylated form. Indirect immunofluorescene microscopy revealed the existence of discrete NAP foci at mid-cell in cells with two nucleoids, but at cell poles in those with one nucleoid. PMID- 9987120 TI - Carbon catabolite repression of the Aspergillus nidulans xlnA gene. AB - Expression of the Aspergillus nidulans 22 kDa endoxylanase gene, xlnA, is controlled by at least three mechanisms: specific induction by xylan or xylose; carbon catabolite repression (CCR); and regulation by ambient pH. Deletion analysis of xlnA upstream sequences has identified two positively acting regions: one that mediates specific induction by xylose; and another that mediates the influence of ambient pH and contains two PacC consensus binding sites. The extreme derepressed mutation creAd30 results in considerable, although not total, loss of xlnA glucose repressibility, indicating a major role for CreA in its CCR. Three consensus CreA binding sites are present upstream of the structural gene. Point mutational analysis using reporter constructs has identified a single site, xlnA.C1, that is responsible for direct CreA repression in vivo. Using the creAd30 derepressed mutant background, our results indicate the existence of indirect repression by CreA. PMID- 9987121 TI - ClpE, a novel member of the HSP100 family, is involved in cell division and virulence of Listeria monocytogenes. AB - We identified, in the facultative intracellular pathogen Listeria monocytogenes, a previously unknown Clp ATPase, unique among the HSP100 proteins because of the presence of a short N-terminal region with a potential zinc finger motif. This protein of 726 amino acids is highly homologous to ClpE of Bacillus subtilis, and is a member of a new subfamily of HSP100/Clp ATPases. The clpE gene is transcribed as a monocistronic mRNA from a typical consensus sigma A promoter. clpE is not stimulated by various stresses, but is upregulated in a clpC mutant. This is the first example of cross-regulation between Clp ATPases. By constructing a clpE mutant of L. monocytogenes, we found that ClpE is required for prolonged survival at 42 degrees C and is involved in the virulence of this pathogen. A double mutant deficient in both ClpE and ClpC was avirulent in a mouse model and completely eliminated in the liver. Electron microscopy studies did not show any morphological alterations in clpE or clpC mutants. In the clpE clpC double mutant, however, cell division was affected, indicating that ClpE acts synergistically with ClpC in cell septation. These results show that the Clp chaperones play a crucial role in both cell division and virulence of L. monocytogenes. PMID- 9987122 TI - The B regulatory subunit of protein phosphatase 2A is required for completion of macroconidiation and other developmental processes in Neurospora crassa. AB - rgb-1, encoding the tentative B regulatory subunit of the type 2A Ser/Thr phosphatase in Neurospora crassa, was isolated from cDNA and genomic libraries. Based on analysis of cDNA and genomic clones, rgb-1 is 3387 nucleotides in length, contains seven putative introns and encodes a 461-amino-acid polypeptide. Intron I, which is 5' to the presumed translation initiation codon, contains a uORF encoding 34 amino acids. Intron VI undergoes alternative splicing. Inactivation of rgb-1 by the repeat-induced point (RIP) mutation procedure produced progeny that grow slowly, have abnormal hyphal morphology, are female sterile and produce abundant amounts of arthroconidia. The rgb-1RIP strain does not produce major constriction chains or mature macroconidia. Minor constriction chains are formed, yet the growth process reverts to hyphal elongation. Microscopic and genetic analyses indicate that rgb-1 is a regulator of the budding subroutine of the macroconidiation process and that arthroconidiation, which shares common early and late events with macroconidiation, is induced as a default mechanism for asexual reproduction in this fungus. PMID- 9987123 TI - The cytoplasmic kinase domain of PhoR is sufficient for the low phosphate inducible expression of pho regulon genes in Bacillus subtilis. AB - PhoP-PhoR, one of three two-component systems known to be required to regulate the pho regulon in Bacillus subtilis, directly regulates the alkaline phosphatase genes that are used as pho reporters. Biochemical studies showed that B. subtilis PhoR, purified from Escherichia coli, was autophosphorylated in vitro in the presence of ATP. Phosphorylated PhoR showed stability under basic conditions but not acidic conditions, indicating that the phosphorylation probably occurs on a conserved histidine residue. Phospho-PhoR phosphorylated its cognate response regulator, PhoP in vitro. B. subtilis phoR was placed in the Bacillus chromosome under the control of the Pspac promoter, which is IPTG inducible. The wild-type phoR, under either native promoter or Pspac promoter with IPTG induction, resulted in a similar level of alkaline phosphatase production. Under high phosphate conditions, strains containing wild-type phoR, or phoR mutant gene products that lacked either the periplasmic domain, or both N-terminal transmembrane PhoR mutant gene products that lacked either the periplasmic domain, or both N-terminal transmembrane PhoR sequences or various extended N terminal sequences, showed no significant APase production. Under phosphate starvation conditions, in the presence of IPTG, all strains containing mutated phoR genes showed alkaline phosphatase induction patterns similar to that of the wild-type strain, although the fully induced level was lower in the mutants. The decrease in total alkaline phosphatase production in these mutant strains can be compensated completely or partially by increasing the copy number of the mutant phoR gene. These in vivo results suggest that the C-terminal kinase domain of PhoR is sufficient for the induction of alkaline phosphatase expression under phosphate-limited conditions, and that the regulation for repression of APase under phosphate-replete conditions remains intact. PMID- 9987124 TI - Molecular characterization of a novel peroxidase isolated from the ligninolytic fungus Pleurotus eryngii. AB - A haem peroxidase different from other microbial, plant and animal peroxidases is described. The enzyme is secreted as two isoforms by dikaryotic Pleurotus eryngii in peptone-containing liquid medium. The corresponding gene, which presents 15 introns and encodes a 361-amino-acid protein with a 30-amino-acid signal peptide, was isolated as two alleles corresponding to the two isoforms. The alleles differ in three amino acid residues and in a seven nucleotide deletion affecting a single metal response element in the promoter. When compared with Phanerochaete chrysosporium peroxidases, the new enzyme appears closer to lignin peroxidase (LiP) than to Mn-dependent peroxidase (MnP) isoenzymes (58-60% and 55% identity respectively). The molecular model built using crystal structures of three fungal peroxidases as templates, also showed high structural affinity with LiP (C alpha distance 1.2 A). However, this peroxidase includes a Mn2+ binding site formed by three acidic residues (E36, E40 and D175) near the haem internal propionate, which accounts for the ability to oxidize Mn2+. Its capability to oxidize aromatic substrates could involve interactions with aromatic residues at the edge of the haem channel. Another possibility is long-range electron transfer, e.g. from W164, which occupies the same position of LiP W171 recently reported as involved in the catalytic cycle of LiP. PMID- 9987125 TI - prhJ and hrpG, two new components of the plant signal-dependent regulatory cascade controlled by PrhA in Ralstonia solanacearum. AB - hrp gene expression in the phytopathogenic bacterium Ralstonia solanacearum GMI1000 is induced through the HrpB regulator in minimal medium and upon co culture with plant cell suspensions. The putative outer membrane protein PrhA is specifically involved in hrp gene activation in the presence of plant cells and has been proposed to be a receptor of a plant-dependent signal transduction pathway. Here, we report on the identification of two regulatory genes, hrpG and prhJ, located at the right-hand end of the hrp gene cluster, that are required for full pathogenicity. HrpG belongs to the OmpR subclass of two-component response regulators and is homologous to HrpG, the activator of hrp genes in Xanthomonas campestris pv. vesicatoria. PrhJ is a novel hrp regulatory protein, sharing homology with the LuxR/UhpA family of transcriptional activators. As for HrpG of X. c. pv. vesicatoria, HrpG is required for hrp gene expression in minimal medium, but, in addition, we show that it also controls hrpB gene activation upon co-culture with Arabidopsis thaliana and tomato cell suspensions. In contrast, PrhJ is specifically involved in hrp gene expression in the presence of plant cells. hrpG and prhJ gene transcription is plant cell inducible through the PrhA-dependent pathway. From these results, we propose a regulatory cascade in which plant cell signal(s) sensed by PrhA are transduced to the prhJ gene, whose predicted product controls hrpG gene expression. HrpG then activates the hrpB regulatory gene, and, subsequently, the remaining hrp transcriptional units in all known inducing conditions. PMID- 9987126 TI - Heterogeneous ribosome populations are present in Plasmodium berghei during development in its vector. AB - The genome of the rodent malaria parasite, Plasmodium berghei, contains two sets of variant ribosomal RNA (rRNA) genes, termed the A and S types, that are expressed predominantly during the vertebrate and mosquito stages of the parasite's development respectively. Using in situ hybridization, we have examined the transcriptional activity of the A- and S-type rRNA genes, and the switch in expression of the ribosome populations that occurs after parasite transmission to the mosquito. By detection of precursor rRNA molecules, we show that A-type rRNA transcription is downregulated throughout development in the mosquito, whereas the initiation of S-type rRNA transcription is linked to the proliferative phase of the oocyst. Mature A-type rRNA persists during development of the zygote into the ookinete/young oocyst. In contrast, mature S-type rRNA is first detectable in young oocysts and is subsequently present at high levels during further development of oocysts and sporozoites. These results demonstrate that the switch in transcription between the A- and S-type rRNA genes is developmentally regulated, taking place only as the parasite begins to proliferate in the mosquito. A-type ribosomes are therefore not only translationally active in the early stages of development in the mosquito, but are also crucial at this phase. PMID- 9987127 TI - Involvement of the FtsH (HflB) protease in the activity of sigma 54 promoters. AB - The effect of FtsH, an essential inner membrane-bound protease, in the regulation of the sigma 54-dependent Pu promoter has been examined in vivo. Escherichia coli cells lacking FtsH failed to activate a Pu-lacZ fusion in response to the cognate enhancer-binding protein XylR. However, the intracellular concentrations of XylR and sigma 54, as well as their apparent physical integrity were the same regardless of the presence or absence of the protease. The loss of Pu activity in FtsH-minus cells was not due to the imbalance between sigma factors caused by the lack of the protease. ftsH mutants could not grow in media with glutamine as the only nitrogen source and failed also to induce the sigma 54 promoters PnifH by NifA and PpspA by PspF. These lesions were fully complemented by a ftsH+ plasmid. Therefore, part of the pleiotropic phenotype of FtsH-less cells corresponded to the lack of sigma 54 activity. Overproduction of sigma 54, however, restored both transcriptional activity of Pu and growth in glutamine of a ftsH strain. These observations suggested that the activity of sigma 54 is checked in vivo by an interplay of factors that ultimately determine the performance of cognate promoters under given physiological conditions. PMID- 9987128 TI - ComEA is a DNA receptor for transformation of competent Bacillus subtilis. AB - Competent cells of Bacillus subtilis efficiently bind and internalize DNA. ComEA and the seven proteins encoded by the comG operon are required in vivo for the binding step. We show here that ComEA, a bitopic membrane protein, is itself capable of high-affinity DNA binding. A domain necessary for DNA binding is located at the C-terminus of ComEA. Proteins with similar 60-80 amino acid residue domains are widespread among bacteria and higher organisms. ComEA shows a marked preference for double-stranded DNA and can bind to oligomers as small as 22 bp in length. DNA binding by ComEA exhibits no apparent base sequence specificity. Using a membrane vesicle DNA-binding assay system we show that in the absence of cell wall, ComEA is still required for DNA binding, whereas the requirement for the ComG proteins is bypassed. We conclude that the ComG proteins are needed in vivo to provide access of the binding domain of ComEA to exogenous DNA. Possible specific roles for the ComG proteins are discussed. PMID- 9987129 TI - Borrelia burgdorferi erpT expression in the arthropod vector and murine host. AB - The expression of a Borrelia burgdorferi gene, erpT, was investigated throughout the spirochaete life cycle in the arthropod vector and the murine host. Three phage clones from a B. burgdorferi DNA expression library synthesized a 30 kDa antigen that was recognized by antibodies in the sera of B. burgdorferi-infected mice but not mice hyperimmunized with B. burgdorferi lysates. Differential antibody binding suggested that this protein was preferentially expressed in vivo. This antigen was designated ErpT, based upon 99.6% homology with the BBF01 sequence in the B. burgdorferi genome. ErpT was not detected on spirochaetes cultured in BSK II medium by indirect immunofluorescence or in B. burgdorferi lysates by immunoblotting, implying that ErpT is not readily produced in vitro. erpT mRNA was not discernible by Northern blot but was identified by RNA polymerase chain reaction in vitro, indicating that erpT is expressed at low levels by cultured spirochaetes. erpT expression was then investigated in the vector and mice because B. burgdorferi do not normally reside in culture medium. RNA polymerase chain reaction and immunofluorescence studies demonstrated that erpT was expressed by a small minority of B. burgdorferi (11/500, 2.2%) within unfed ticks and then repressed during engorgement. erpT mRNA or ErpT antibodies were first detected in B. burgdorferi-infected mice at 4 weeks, suggesting that erpT was not expressed in the early stages of murine infection. Then, during persistent infection, RNA polymerase chain reaction showed that erpT was expressed by B. burgdorferi within the joints, heart and spleen, but not by spirochaetes in the skin. Immunization of mice with ErpT was antigenic but was not protective. These studies demonstrate that B. burgdorferi erpT is differentially expressed throughout the B. burgdorferi life cycle, in both the vector and the mammalian host, and is primarily expressed in extracutaneous sites during murine infection. PMID- 9987130 TI - Independent acquisition and insertion into different chromosomal locations of the same pathogenicity island in Yersinia pestis and Yersinia pseudotuberculosis. AB - We show that Yersinia pestis and pesticin-sensitive isolates of Y. pseudotuberculosis possess a common 34 kbp DNA region that has all the hallmarks of a pathogenicity island and is inserted into different asparaginyl tRNA genes at different chromosomal locations in each species. This pathogenicity island (YP HPI) is marked by IS100, has a G + C content different from its host, is flanked by 24 bp direct repeats, encodes a putative, P4-like integrase and contains the iron uptake virulence genes from the pgm locus of Y. pestis. These findings indicate independent horizontal acquisition of this island by Y. pestis and Y. pseudotuberculosis. The two YP-HPI locations and their possession of an integrase gene support a model of site-specific integration of the YP-HPI into these bacteria. PMID- 9987132 TI - The structural and functional organization of H-NS-like proteins is evolutionarily conserved in gram-negative bacteria. AB - The structural gene of the H-NS protein, a global regulator of bacterial metabolism, has been identified in the group of enterobacteria as well as in closely related bacteria, such as Erwinia chrysanthemi and Haemophilus influenzae. Isolated outside these groups, the BpH3 protein of Bordetella pertussis exhibits a low amino acid conservation with H-NS, particularly in the N terminal domain. To obtain information on the structure, function and/or evolution of H-NS, we searched for other H-NS-related proteins in the latest databases. We found that HvrA, a trans-activator protein in Rhodobacter capsulatus, has a low but significant similarity with H-NS and H-NS-like proteins. This Gram-negative bacterium is phylogenetically distant from Escherichia coli. Using theoretical analysis (e.g. secondary structure prediction and DNA binding domain modelling) of the amino acid sequence of H-NS, StpA (an H NS-like protein in E. coli), BpH3 and HvrA and by in vivo and in vitro experiments (e.g. complementation of various H-NS-related phenotypes and competitive gel shift assay), we present evidence that these proteins belong to the same class of DNA binding proteins. In silico analysis suggests that this family also includes SPB in R. sphaeroides, XrvA in Xanthomonas oryzae and VicH in Vibrio cholerae. These results demonstrate that proteins structurally and functionally related to H-NS are widespread in Gram-negative bacteria. PMID- 9987131 TI - ToxR co-operative interactions are not modulated by environmental conditions or periplasmic domain conformation. AB - ToxR is a transmembrane regulatory protein that controls virulence gene expression in Vibrio cholerae. Previous experiments using lambda repressor-ToxR chimeric proteins and a lambda repressor-controlled reporter system (OR1 PR lacZY) established that ToxR sequences can effectively dimerize the amino terminal domain of lambda repressor in Escherichia coli. However, in E. coli, ToxR does not respond to environmental signals that control virulence gene expression in V. cholerae. Here, we report the results of experiments designed to test whether environmental signals that modulate virulence gene expression in V. cholerae also modulate a monomer to dimerization transition of lambda-ToxR chimeras. When the OR1 PR-lacZY reporter fusion and chimeric proteins were transferred to V. cholerae, we unexpectedly found that lambda-ToxR chimeras did not dimerize significantly. Interestingly, experiments evaluating the ability of lambda-ToxR proteins to form tetramers in E. coli suggested that lambda-ToxR dimers could act co-operatively. Using a redesigned reporter system containing multiple lambda operator sites (OR1 OR2 OR3 PR-lacZY), we found that lambda-ToxR could dimerize quite efficiently in V. cholerae. These data imply that multiple DNA binding sites might enhance the ability of ToxR to dimerize in V. cholerae and suggest that ToxR dimers might be capable of co-operative interactions. However, we falled to correlate a monomer-dimer transition of the lambda-ToxR chimeras with changes in virulence gene expression in response to environmental signals in V. cholerae. Finally, because of conflicting results in the literature, the importance of membrane localization of ToxR and dimerization of the ToxR periplasmic domain was re-evaluated. This was accomplished by measuring the ability of various chimeric proteins to activate toxin gene expression in both E. coli and V. cholerae. These assays suggest that, in V. cholerae, deletion of the transmembrane domain has a profound effect on ToxR activity, although it is not an absolute requirement when ToxR is dimerized by a heterologous domain. In addition, we noted differences in chimeric protein activity when expressed in E. coli and V. cholerae. A construct substituting the monomeric MalE domain for the periplasmic domain of ToxR was unable to activate a ctx::lacZ reporter fusion in E. coli. Although the addition of leucine zipper sequences to this construct resulted in enhanced activity of the chimera in E. coli, both chimeras were able to produce wild-type levels of toxin in V. cholerae. These data support the notion that dimerization of ToxR stimulates its activity as a transcriptional activator in E. coli. In V. cholerae, however, we present data that do not demonstrate a correlation between dimerization of the periplasmic domain and ToxR activity. PMID- 9987133 TI - Masc2, a gene from Ascobolus encoding a protein with a DNA-methyltransferase activity in vitro, is dispensable for in vivo methylation. AB - We have shown previously that masc1, a gene encoding a putative C5-DNA methyltransferase (MTase), was necessary for the de novo 'Methylation Induced Premeiotically' (MIP) process and sexual reproduction in Ascobolus, whereas it was dispensable for maintenance methylation. A second MTase gene from Ascobolus, masc2, encodes a protein, Masc2, which possesses the large amino-terminal part characteristic of eukaryotic maintenance MTases. In vitro assays have shown that Masc2 displays a methylation activity, suggesting that it might be the MTase responsible for maintenance methylation. To check its function in vivo, we engineered a disruption of the masc2 gene. The resulting mutant strains did not exhibit any particular phenotype during either vegetative growth or sexual reproduction. Neither the masc2 mutation nor the double masc1 masc2 mutation had any detectable effect upon the maintenance of the pre-existing methylation of single gene copies previously subjected to MIP, natural retroelement-like repeats and tandemly repeated rDNA. The masc2 mutation did not alter either MIP or the other de novo methylation process that operates in vegetatives cells. Nor did it impair the meiotic process of methylation transfer. These results suggest that at least a third MTase gene responsible for maintenance and vegetative de novo methylation is present in Ascobolus. PMID- 9987134 TI - Mannopinic acid and agropinic acid catabolism region of the octopine-type Ti plasmid pTi15955. AB - Octopine-type Ti plasmids such as pTi15955, pTiA6 and pTiR10 direct the catabolism of at least eight compounds called opines that are released from crown gall tumours. Four of these compounds are denoted mannityl opines, each of which possesses a D-mannityl substituent on the nitrogen atom of either glutamate or glutamine. We have analysed a 20 kb region of the Ti plasmid pTi15955 that is required for the catabolism of two such opines, mannopinic acid and agropinic acid. A total of 12 genes in four operons were identified by DNA sequence analysis. Transposons Tn5lacZ and MudK were used to mutagenize these genes and to create aga-lacZ and moa-lacZ translational fusions. The expression of all fusions was induced by agropinic acid and by mannopinic acid. One of these four operons encodes an agropinic acid permease, whereas a second one encodes a mannopinic acid permease. A third operon contains three genes encoding probable catabolic enzymes, two of which (AgaF and AgaG) are thought to convert agropinic acid to mannopinic acid, while the third (AgaE) probably converts mannopinic acid to mannose and glutamate. AgaE resembles a bacterial amino acid deaminase, whereas AgaF and AgaG resemble two bacterial proteins that together catabolize substituted hydantoins, whose chemical structure resembles that of agropinic acid. The remaining operon encoded the MoaR protein, a negative regulator of itself and of the other three operons. PMID- 9987135 TI - MCM21 and MCM22, two novel genes of the yeast Saccharomyces cerevisiae are required for chromosome transmission. AB - The minichromosome maintenance genes, MCM21 and MCM22, have been cloned and are shown to code for the ORFs YDR318W and YJR135C respectively. Mutations in these genes caused a decrease in the stability of the minichromosome. This decrease in stability was associated with an increase in the copy number of the minichromosome in cells carrying it. Small circular dicentric plasmids were maintained relatively stably and structurally intact in the mutants compared with the wild-type strain. In the latter, such plasmids were mitotically unstable and, upon recovery, showed frequent rearrangements of their DNA. A centromere offered less obstruction to transcription in mutant cells than in the wild type, showing that both these mutants had a more relaxed kinetochore assembly. The mutant strains showed elevated rates of chromosome loss but not those of recombination. Both the mutations caused the cells to display a higher sensitivity towards the anti-mitotic drug benomyl. All these observations suggest that MCM21 and MCM22 are important for chromosome segregation with a potential role in kinetochore function. These genes are non-essential, as their deletions from chromosomes did not cause loss of cell viability. However, exponentially growing mutant cells carrying the deletion of the MCM21 gene had a significant population of large budded cells with a single nucleus at the neck. Furthermore, the DNA content of these cells showed a shift towards 2N, suggesting a temporary pause of cells in G2 or in an early phase of mitosis. The mcm21 and mcm22 mutations do not show synthetic lethality or any further enhancement of growth defects, implying that they could be carrying out non-overlapping functions in chromosome segregation. PMID- 9987136 TI - Identification of target promoters for the Bacillus subtilis extracytoplasmic function sigma factor, sigma W. AB - The Bacillus subtilis sigW gene encodes an extracytoplasmic function (ECF) sigma factor that is expressed in early stationary phase from a sigW-dependent autoregulatory promoter, PW. Using a consensus-based search procedure, we have identified 15 operons preceded by promoters similar in sequence to PW. At least 14 of these promoters are dependent on sigma W both in vivo and in vitro as judged by lacZ reporter fusions, run-off transcription assays and nucleotide resolution start site mapping. We conclude that sigma W controls a regulon of more than 30 genes, many of which encode membrane proteins of unknown function. The sigma W regulon includes a penicillin binding protein (PBP4*) and a co transcribed amino acid racemase (RacX), homologues of signal peptide peptidase (YteI), flotillin (YuaG), ABC transporters (YknXYZ), non-haem bromoperoxidase (YdjP), epoxide hydrolase (YfhM) and three small peptides with structural similarities to bacteriocin precursor polypeptides. We suggest that sigma W activates a large stationary-phase regulon that functions in detoxification, production of anti-microbial compounds or both. PMID- 9987137 TI - Cardiolipin synthase expression is essential for growth at elevated temperature and is regulated by factors affecting mitochondrial development. AB - Cardiolipin (CL) is a unique dimeric phospholipid localized primarily in the mitochondrial membrane. In eukaryotes, the enzyme CL synthase catalyses the synthesis of CL from two lipid substrates, CDP-diacylglycerol and phosphatidylglycerol. In earlier studies, we reported the purification of CL synthase from Saccharomyces cerevisiae and the cloning of the gene CRD1 (previously called CLS1) that encodes the enzyme. Because CL is an important component of the mitochondrial membrane, knowledge of its regulation will provide insight into the biogenesis of this organelle. To understand how CL synthesis is regulated, we analysed CRD1 expression by Northern blot analysis of RNA extracted from cells under a variety of growth conditions. CRD1 expression is regulated by mitochondrial development factors. CRD1 levels were 7- to 10-fold greater in stationary than in logarithmic growth phase, and threefold greater in wild-type than in rho 0 mutants. Expression was somewhat elevated during growth in glycerol/ethanol versus glucose media. In contrast, CRD1 expression was not regulated by the phospholipid precursors inositol and choline, and was not altered in the regulatory mutants ino2, ino4 and opi1. Mutations in cytochrome oxidase assembly, which led to reduced Crd1p enzyme activity, did not affect CRD1 expression. The crd1 null mutant makes a truncated CRD1 message. Although the null mutant can grow on both fermentable and non-fermentable carbon sources at lower temperatures, it cannot form colonies at 37 degrees C. In conclusion, CRD1 expression is controlled by factors affecting mitochondrial development, but not by the phospholipid precursors inositol and choline. Expression of CRD1 is essential for growth at elevated temperatures, suggesting that either CL or Crd1p is required for an essential cellular function. PMID- 9987138 TI - Characterization of the C-terminal domain essential for toxic activity of adenylate cyclase toxin. AB - Adenylate cyclase toxin (CyaA) of Bordetella pertussis belongs to the RTX family of toxins. These toxins are characterized by a series of glycine- and aspartaterich nonapeptide repeats located at the C-terminal half of the toxin molecules. For activity, RTX toxins require Ca2+, which is bound through the repeat region. Here, we identified a stretch of 15 amino acids (block A) that is located C-terminally to the repeat and is essential for the toxic activity of CyaA. Block A is required for the insertion of CyaA into the plasma membranes of host cells. Mixing of a short polypeptide composed of block A and eight Ca2+ binding repeats with a mutant of CyaA lacking block A restores toxic activity fully. This in vitro interpolypeptide complementation is achieved only when block A is present together with the Ca2+ binding repeats on the same polypeptide. Neither a short polypeptide composed of block A only nor a polypeptide consisting of eight Ca2+ binding repeats, or a mixture of these two polypeptides, complement toxic activity. It is suggested that functional complementation occurs because of binding between the Ca2+ binding repeats of the short C-terminal polypeptide and the Ca2+ binding repeats of the CyaA mutant lacking block A. PMID- 9987139 TI - RpoN-dependent transcription of rpoH? PMID- 9987140 TI - The multidrug efflux protein NorM is a prototype of a new family of transporters. PMID- 9987141 TI - Safety and immunogenicity of an inactivated subunit influenza virus vaccine combined with MF59 adjuvant emulsion in elderly subjects, immunized for three consecutive influenza seasons. AB - A clinical trial to evaluate the safety and tolerability of a new influenza adjuvanted vaccine (FLUAD, Chiron Vaccines), compared with a conventional non adjuvanted influenza vaccine, was conducted in elderly ambulatory patients. Subjects were vaccinated with one dose of either vaccine each year for three consecutive years; 92 subjects received the first immunization, 74 subjects received the second and 67 subjects received the third. The primary objective of this study was to evaluate the safety of repetitive injections of the adjuvanted vaccine in elderly subjects. There were no reports of any vaccine-related serious adverse event or of safety concerns related to study vaccines after the first, second or third immunization. The adjuvanted vaccine induced more local reactions than the conventional vaccine; however, the reactions were normally mild and limited to the first 2-3 days after immunization. No statistically significant difference between groups in systemic postimmunization reactions was reported except for a mild, transient malaise after the first immunization. Compared with the first immunization, no increase in postimmunization reactions was seen after the second and third immunizations. Despite the small sample size of the trial, which was not powered to test immunogenicity differences, the antibody response was tested and resulted higher in the adjuvanted vaccine recipients, not only against the current season's vaccine strains, but also against heterologous vaccine strains. PMID- 9987142 TI - Comparison of the safety and immunogenicity of the lyophilized Merieux seed and the World Health Organization working reference BCG vaccines in school-aged children in Senegal. AB - In order to validate two new lots of Merieux BCG vaccine (Merieux seed derived from strain 1072), a calibration study was performed to compare their safety and immunogenicity to a full dose of the WHO-reference BCG vaccine (Tokyo strain 172) as well as the WHO-reference vaccine given at 1/10 of its normal concentration, in an open, randomized, four-arm, multicenter study in Senegal. A total of 1041 healthy Senegalese children aged 8-10 years were screened for participation in this study, of whom 548 had a negative Mantoux test and complied with inclusion and exclusion criteria. These children were randomly allocated a single dose of one of the following vaccines: full-dose Merieux BCG vaccine (lot E0650); full dose Merieux BCG vaccine (lot E0624); full-dose WHO-reference vaccine (Tokyo strain 172); or 1/10 dose WHO-reference vaccine. A follow-up examination, including a tuberculin test, was performed 10-12 weeks after BCG vaccination for 465 (85%) children: 236 Merieux BCG vaccine (117 lot E0650; 119 lot E0624); 115 full-dose WHO; 114 1/10 dose WHO. The percentage of subjects with a positive tuberculin test after vaccination was significantly lower (P < 0.001) in the 1/10 dose group (81.5%) compared to the other three groups (> 96%). The mean induration diameter was significantly smaller in subjects who received the low dose of WHO vaccine compared to the others, according to analyses considering all subjects vaccinated, as well as only those subjects with a positive tuberculin test after vaccination. More children in the low-dose group did not have a vaccination scar, and the mean diameter of scars was smaller in this group. The rate of tuberculin reactions, the classification of reactions (Palmer and Edwards), and the characteristics of the vaccinal lesion were similar for the Merieux BCG vaccines and the full-dose WHO-reference vaccine. All vaccines were safe, as evidenced by the absence of adenitis or suppurative adenitis during the course of the study. Results from this trial show that the two lots of Merieux BCG vaccine behave equally as well as the full-dose WHO-reference BCG vaccine. The WHO-reference vaccine, given at 1/10 of its normal concentration was significantly less immunogenic, according to all parameters evaluated. PMID- 9987143 TI - Persistence of antibodies to the Salmonella typhi Vi capsular polysaccharide vaccine in South African school children ten years after immunization. AB - Between 10 and 11 years after children were vaccinated with Vi capsular polysaccharide of Salmonella typhi or meningococcal A + C control vaccine in a double blind randomized trial, we traced 83 subjects, aged 16-20 years. A blood sample was taken for determination of Vi antibody titres in both groups by radioimmunoassay. TO and TH titres were also done to assess if the participants had had recent exposure to typhoid fever. Fifty-eight percent of subjects in both groups had protective levels of Vi antibody against Salmonella typhi (a titre greater than 1 microgram ml-1). There was no significant difference in the levels of Vi antibodies in the cases versus the controls (p = 0.5). Two of the children who had received meningococcal A + C vaccine had recently had typhoid fever. Our data show that adolescents in typhoid endemic areas have high levels of Vi antibodies regardless of previous vaccination status, suggesting that Vi antibodies are acquired in adolescence by a large percentage of the population in this area. Moreover, Vi vaccination has led to ongoing antibody production in greater than 50% of Vi vaccinated children in an endemic area for a period of 10 years. Ongoing antigenic exposure may have contributed to these antibody levels. PMID- 9987144 TI - For discussion: live attenuated vaccines for group B meningococcus. AB - Current attempts at preventing infections caused by group B Neisseria meningitidis are largely directed on generating immune responses to outer membrane proteins or the lipopolysaccharide of this organism. We suggest an alternative approach: the use of a live, attenuated strain of Neisseria meningitidis which could be delivered mucosally to elicit both local and systemic immune responses. PMID- 9987145 TI - A routine high-performance size-exclusion chromatography to determine molecular size distribution of Haemophilus influenzae type b conjugate vaccines. AB - High-performance size exclusion chromatography has been used to determine the molecular size distribution of Haemophilus influenzae type b (Hib) conjugate vaccines. Both high molecular weight preparations of native Hib capsular polysaccharide coupled to tetanus toxoid and low molecular weight vaccines with Hib oligosaccharides linked to the CRM197 nontoxic mutant diphtheria protein were analysed. Columns with different fractionation ranges were used for the two kinds of vaccines. This method showed to be rapid, accurate and reproducible for different lots of Hib vaccine of different composition produced by various manufacturers. It could replace more time-consuming chromatographic methods enabling control authorities to employ a single methodological approach for different Hib vaccines. PMID- 9987146 TI - Epitopic overload at the site of injection may result in suppression of the immune response to combined capsular polysaccharide conjugate vaccines. AB - Capsular polysaccharide (CP) conjugate vaccines targeting a variety of bacterial infections are currently under development and clinical evaluation. The inclusion of multiple CP serotypes combined in a single injection is an important maneuver being evaluated. The combination of CP conjugate vaccines into a single multivalent injection may result in competition among the different components and adversely affect the immunogenicity of any individual conjugate. We observed a reduction of 30-90% in antibody responses to several serotypes in mice when immunogenicity of a 12-valent Escherichia coli (E. coli) lipopolysaccharide (LPS) conjugate vaccine was compared to the immunogenicity of each monovalent vaccine evaluated separately. A reduction of 30% was observed in the Staphylococcus aureus (S. aureus) type 8 CP antibodies when a type 8-rEPA conjugate was combined with a type 5-rEPA conjugate. S. aureus types 5 and 8-rEPA conjugates were combined with 100 micrograms of either rEPA (homologous) or diphtheria toxoid (DT) (heterologous) carrier proteins, and evaluated in rEPA or DT primed mice. The addition of the homologous protein resulted in a 64% reduction in type 5 CP antibodies. The heterologous protein did not affect the immunogenicity of the type 5. We postulate that the free protein competed with the conjugate and recruited most of the rEPA primed T cells. In the case of the DT conjugates, the DT targeted different populations of the T cells, thus interference was not observed. These data suggested that the epitopic load rather than the antigenic load at the site of injection caused reduced immunogenicity of the conjugates. We theorize that individual components of multivalent CP vaccines conjugated to the same carrier proteins would compete for a limited number of specific carrier protein primed T cells. This would result in one or more components being unavailable in eliciting a sufficient immune response. The use of multiple carrier proteins should be considered as an approach to reduce interference when multivalent conjugate vaccines are to be formulated into a single injection. PMID- 9987147 TI - Effectiveness of a nationwide infant immunization program against Haemophilus influenzae b. The Israeli Pediatric Bacteremia and Meningitis Group. AB - An ongoing nationwide prospective surveillance program for invasive H. influenzae b (Hib) disease in Israel enabled us to study the effectiveness of a national infant Hib immunization program, which included all infants born since January 1994. The vaccine used was Hib polysaccharide conjugated to outer membrane protein complex of Neisseria meningitidis b (PRP-OMPC). For the cohort born during the 3 years since January 1994, the vaccine effectiveness was 94.9% for all invasive Hib diseases and 96.6% for meningitis. The efficacy in fully immunized subjects was 98.7 and 99.5%, respectively. A herd immunity effect could be observed, since a reduction in cases also occurred among infants too young to be immunized. No increase in invasive cases caused by S. pneumoniae and N. meningitidis was observed during the study period. This is the first report outside North America and Western Europe that demonstrates a nationwide extensive reduction of invasive Hib disease within a short time of the introduction of Hib conjugate vaccines to the infant immunization program. PMID- 9987148 TI - The value of varicella vaccination in healthy children: cost-benefit analysis of the situation in France. AB - The purpose of the cost-benefit analysis described in this article is to determine the economic value of vaccination of healthy children against varicella in France. It is based on the results of two specific investigations--an epidemiological model and a prospective observational study (1832 cases studied) of the socio-economic consequences of varicella. This cost-benefit analysis was conducted from the viewpoint of the society and that of the patient, for vaccination coverage rates ranging from 10 to 90%. This analysis demonstrates the value of varicella vaccination when associated with measles-mumps-rubella (MMR) vaccination: if varicella and MMR vaccines are co-administered, the vaccination of 80% of the children against varicella leads to a reduction in medical costs associated with varicella including that of vaccination, ranging from 10 to 77% according to the values adopted for vaccination costs, varicella treatment costs, discount rate and vaccine efficacy. The results of this study also underline the benefits of a vaccination policy that aims to achieve a high rate of coverage, thereby reaping the highest benefit from vaccination, and also avoiding potential negative consequences. PMID- 9987149 TI - Murine gamma-herpesvirus 68 glycoprotein 150 protects against virus-induced mononucleosis: a model system for gamma-herpesvirus vaccination. AB - Murine gamma-herpesvirus 68 (MHV-68) is a model for the study of the pathogenesis of gamma-herpesviruses. Epstein-Barr virus (EBV) is a highly related gamma herpesvirus that causes significant disease in humans. The major membrane antigen gp350 of EBV is a candidate vaccine antigen for protection against EBV-related disease. An MHV-68 glycoprotein, gp150, has significant homology to EBV gp350. We have therefore used the MHV-68 gp150 to model the potential efficacy of EBV gp350 in protecting from virus-associated disease. A recombinant vaccinia virus expressing MHV-68 gp150 was constructed. This recombinant vaccinia virus was used to infect mice via the subcutaneous route. This vaccination resulted in production of MHV-68-neutralising antibodies. Mice were then challenged intra nasally with MHV-68. MHV-68-associated mononucleosis was virtually abrogated in immunised mice. However, mice did establish MHV-68 latency. The results suggest that gp350 may be effective as an immunogen to prevent EBV-associated infectious mononucleosis in humans that are EBV-seronegative. PMID- 9987150 TI - Human immune response to a Pseudomonas aeruginosa outer membrane protein vaccine. AB - In order to evaluate in humans the safety and immunogenicity of a Pseudomonas aeruginosa vaccine composed of outer membrane proteins (OMPs), CFC-101, we carried out a phase I/IIa clinical trial in healthy male volunteers. Groups of six volunteers were immunized either subcutaneously (s.c.) or intramuscularly (i.m.) with three dosages of the vaccine three times at 7-day intervals. The vaccine was well tolerated by volunteers. Local reactions in the injection sites were generally mild and transient. Significant increases in OMP-specific antibody were observed in both route groups after vaccinations but was higher in the i.m. immunized group, where vaccination with 0.5 or 1.0 mg doses yielded 100% seroconversion. The specificity of the induced antibodies to P. aeruginosa OMP was demonstrated by western blot analysis and immunoprecipitation assay. An increase in Clq-binding capacity and ability to confer mice protection from lethal challenges with P. aeruginosa indicated the protective efficacy of the elicited antibodies. Based on these data, we concluded that the P. aeruginosa OMP vaccine is safe and effective in humans with an optimal dose of 0.5 and 1.0 mg and that i.m. is the better route than s.c. for this vaccine. PMID- 9987151 TI - Association of human leucocyte antigen phenotype with vaccine efficacy in patients receiving vaginal mucosal immunization for recurrent urinary tract infection. AB - Immune responses to specific antigens can be influenced by an individual's genetic make-up. We examined whether the efficacy of a vaginal mucosal vaccine for urinary tract infections (UTI) was affected by a patient's human leucocyte antigen (HLA) phenotype. Urinary tract infection data and the HLA phenotypes of 47 women participating in a phase II clinical trial of immunization for recurrent UTI were statistically analysed for associations between HLA-A, -B, -DR, or -DQ phenotype and postimmunization infection course. Women who received the vaccine and had HLA-DR phenotypes other than DR2 had significantly delayed times to re infection compared with women receiving placebo. Vaccine-treated patients with the HLA-DR2 phenotype had re-infection courses that were not different than women receiving placebo. These results indicate that the efficacy of a vaginal mucosal UTI vaccine may be influenced by an individual's HLA-DR phenotype. PMID- 9987152 TI - Immunological properties of plaque purified strains of live attenuated respiratory syncytial virus (RSV) for human vaccine. AB - Respiratory syncytial virus (RSV) causes severe lower respiratory tract disease in infants, young children, and the elderly. Efforts to develop satisfactory live or inactivated vaccines have not yet been proven successful. Our research focuses on the development of four purified live attenuated RSV sub-type A human vaccine clones. Temperature sensitive (ts) and attenuated purified clones of either cold adapted (ca) RSV or high-passage (hp) RSV were administered intra-nasally (i.n.) to BALB/c mice and tested for immunogenicity. All four clones produced significant anti-RSV F IgG2a and IgG1 titres in the sera of mice, RSV-specific neutralizing titres higher than those produced by their wild-type progenitor viruses, cytotoxic T-lymphocyte (CTL) activity, and total protection against wild type (wt) viral challenge. These purified vaccine candidates await testing in humans to determine which contain the required balance between immunogenicity and attenuation. PMID- 9987153 TI - A comparison of alternate immunization regimes for measles in vaccinated populations. AB - Infants today lose maternal measles antibody sooner than in the past. This is related to demographic changes in maternal immunization. Data for rates of decay of maternal antibody and seroconversion after measles vaccination for infants born to naturally immune (Group 1) or vaccinated (Group 2) mothers have been used to evaluate two vaccination schedules: Regime 1, measles-mumps-rubella (MMR) at 1 year of age and Regime 2, monovalent measles at 6 months followed by MMR at 15 months of age. Regime 2 costs less because MMR can be administered at 15 months with the last pentavalent booster. Months of protection/1000 children aged 0-15 months (child-months of protection) were estimated for infant populations ranging from 0 to 100% Group 1 for Regimes 1 and 2. Regime 1 provides more child-months of protection only for 100% Group 1 populations. For the study population Regime 2 provided at least 17% more child-months of protection than Regime 1. Regime 2 provides increased medical and financial benefits in proportion to the number of Group 2 infants in the population and thus is ever more advantageous for today's increasingly vaccinated populations. PMID- 9987154 TI - Multivalent group A streptococcal vaccine designed to optimize the immunogenicity of six tandem M protein fragments. AB - One of the major challenges in the development of group A streptococcal M protein based vaccines is the multiplicity of M types expressed by these organisms. Previous studies have shown that multivalent vaccines containing as many as eight M protein fragments in tandem were immunogenic and evoked opsonic antibodies. It was also noted that the C-terminal fragments of these hybrid proteins were often not immunogenic or evoked only low levels of opsonic antibodies, suggesting that the C-terminus of the molecule may have been preferentially degraded or altered in vivo. In the present studies, we designed a hexavalent vaccine containing protective M protein peptides from types 24, 5, 6, 19, 1, and 3 group A streptococci. In order to "protect" the carboxy-terminal components, the amino terminal M24 fragment was reiterated on the carboxy-terminal end of the construct. The hexavalent vaccine was immunogenic in laboratory animals and evoked high titers of antibodies against each of the native M proteins represented in the vaccine and bactericidal antibodies against all six sterotypes of group A streptococci. The vaccine was equally immunogenic when delivered in alum or in complete Freund's adjuvant. None of the immune sera contained antibodies that crossreacted with human heart tissue. Our results show that complex multivalent group A streptococcal vaccines can be designed in such a way that each M protein fragment is immunogenic and evokes protective antibodies. PMID- 9987155 TI - Kinetics of formation of neutralizing antibodies against vaccinia virus following re-vaccination. AB - Administration of vaccinia immune globulin (VIG), derived from vaccinated healthy adult volunteers, is the treatment-of-choice for patients suffering from severe complications following smallpox vaccination. The present study was aimed to determine the time interval after vaccination, at which the highest titer of neutralizing antibodies is obtained. Ninety-nine 18-year-old soldiers, immunized with vaccinia virus at birth, participated in the study, 87 of whom had detectable antibodies against vaccinia virus prior to re-vaccination. Their initial average neutralizing antibodies titer (NT50) was 27. Fourteen days after re-vaccination the titer reached 152 and then dropped to 136, 119, 110 and 87 at 21, 30, 45 and 60 d, respectively. The titers of vaccinia antibodies induced in vaccinees without detectable antibodies at the start of the study, were significantly lower and the titers observed after re-vaccination were: 62, 56, 66, 38 and 34, at 14, 21, 30, 45 and 60 d, respectively. In an additional study, 65 volunteers vaccinated at birth and again at the age of 8 years old were re vaccinated. Fourteen days later their NT50 was higher than those vaccinated only at birth. It can be concluded that bleeding of vaccinees 14 d following re vaccination is the preferable time for the preparation of VIG. PMID- 9987156 TI - Studies on the structures and antigenic properties of rabies virus glycoprotein analogues produced in yeast cells. AB - We investigated two forms (designated as yGI and yGII) of rabies virus glycoprotein (G) analogues produced in the G cDNA-transfected yeast cells. Molecular weights of yGI and yGII were estimated as 66 and 56 kDa, respectively, according to their relative mobility in SDS-PAGE. Although being produced in large amounts, yGI was present mostly in insoluble forms and hardly extractable with non-ionic detergents. The yGI reacted with polyclonal anti-G antibodies, but did not react with our conformational epitope-specific anti-G monoclonal antibodies (G-MAbs). No protective immunity was induced by yGI in guinea pigs nor in mice. On the other hand, yGII was Triton-soluble, but was only small in amount (at most 1% of total G proteins) and was shown to lack the cytoplasmic domain. The yGII, however, reacted with the G-MAbs and induced protective immunity in guinea pigs as well. When the G-cDNA was expressed in animal cells in culture, a single form (about 66 kDa) of G protein was produced, which displayed similar behaviors as seen in its reactivity with the MAbs and intracellular distribution as seen in the virus-infected cells. These results suggest that most G protein molecules were not processed normally in yeast cells, resulting in abnormal folding and multimer formation, while only a small fraction were occasionally folded normally to have conformational epitopes but were mostly deprived of the C terminal portion. PMID- 9987157 TI - Sulfolipo-cyclodextrin in squalane-in-water as a novel and safe vaccine adjuvant. AB - Previously, we described synergistic adjuvanticity of combinations of synthetic sulfolipo(SL)-derivatives of polysaccharide (SL-polysaccharides) and squalane-in water emulsions (squalane/W). In this paper, effects of type of polysaccharide and nature of oil on adjuvanticity, reactogenicity and stability are described. SL-derivatives of the following polysaccharides were synthesised: synthetic polysucroses with weight-average molecular weight (MW) of 400,000 (Ficoll400), 70,000 (Ficoll70) and 39,000 Da (Ficoll39), polyfructose of 5,000 Da (inulin), linear polyglucose of 1,200 Da (maltodextrin) and cyclic polyglucose of 1,135 Da (beta-cyclodextrin). The number of sulphate groups per monosaccharide of the different SL-polysaccharides varied between 0.15 and 0.23 and the number of lipid groups per monosaccharide between 1.15 and 1.29. Adjuvant formulations were prepared by incorporating these SL-polysaccharides into oil-in-water emulsions of either squalane, hexadecane, soya oil or mineral oil. Adjuvanticity of the formulations obtained for humoral responses to inactivated pseudorabies virus (PRV) and inactivated influenza virus strains A/Swine (A/Swine) and MRC-11 (MRC 11) in pigs and MRC-11 and ovalbumin (OVA) in mice depended on the type of oil (squalane = mineral oil > hexadecane = soya oil) but not on the type of polysaccharide backbone of the SL-derivative. Reactogenicity assessed by local swelling in mice decreased with decreasing MW (SL-Ficoll400 = Ficoll70 = Ficoll39 > SL-inulin = SL-maltodextrin > SL-cyclodextrin) when combined with squalane and decreased with the type of oil in the following order: squalane > mineral oil > hexadecane > soya oil when combined with SL-Ficoll400. Stability of the SL polysaccharide/squalane/W emulsions at elevated temperature increased with decreasing MW of the SL-polysaccharide (SL-Ficoll400 < SL-Ficoll70 = SL-Ficoll39 < SL-inulin = SL-maltodextrin = SL-cyclodextrin). SL-cyclodextrin/squalane/W remained stable for > 2.5 years at 4 degrees C, > 18 weeks at 37 degrees C and > 10 days at 60 degrees C. We concluded that reactogenicity and stability but not adjuvanticity of SL-polysaccharide/squalane/W formulations depended on the MW of SL-polysaccharide and that SL-cyclodextrin/squalane/W is a promising non-mineral oil adjuvant as it combines strong adjuvanticity (i.e. better than the mineral oil-based adjuvant presently applied) with low reactogenicity and good stability. PMID- 9987158 TI - Homing potentials of circulating antibody-secreting cells after administration of oral or parenteral protein or polysaccharide vaccine in humans. AB - The site of antigen encounter influences the Ig-distribution and homing potentials of circulating antibody-secreting cells (ASC) induced. After oral antigen administration, the majority ASC secrete the mucosal Ig-isotype, IgA, and all of them express the gut homing receptor (HR), alpha 4 beta 7, thus implying mucosal homing of these cells. Parenteral protein vaccine induces an IgG dominated response with a low proportion of alpha 4 beta 7 expressing cells. However, a polysaccharide vaccine, even if administered parenterally, elicits an IgA-dominated response, hence suggesting homing to the mucosa. In order to study the influence of the nature of the antigen on the targeting of the ASC response, the present work compares the homing potentials of circulating ASC in humans after administration of an oral Salmonella Typhi Ty21a vaccine (antigen studied: O-9,12 polysaccharide), an oral recombinant cholera vaccine (antigen studied: cholera toxin B-subunit, CTB protein), a parenteral pneumococcal vaccine (antigen studied: Pnc capsular polysaccharide 19F) or a parenteral tetanus toxoid vaccine (antigen studied: TT protein). alpha 4 beta 7 was expressed on a higher proportion of ASC induced by oral O-9,12 (99%) and CTB (99%) than by parenteral Pnc (70%) or TT (63%). L-selectin, the peripheral lymph node HR, was expressed on a smaller proportion of ASC induced by O-9,12 (37%) or CTB (43%) than of those induced by Pnc (78%) or TT (81%). The results imply that even if the nature of the antigen has a profound effect on the Ig-distribution of the ASC response, it does not seem to influence the targeting of the response. PMID- 9987159 TI - DNA-mediated immunization with glycoprotein D of equine herpesvirus 1 (EHV-1) in a murine model of EHV-1 respiratory infection. AB - DNA-mediated immunization was assessed in a murine model of equine herpesvirus 1 (EHV-1) respiratory infection. A single intramuscular injection with plasmid DNA encoding EHV-1 glycoprotein D (EHV-1 gD), including its predicted C-terminal membrane anchor sequence, induced a specific antibody response detectable by 2 weeks and maintained through 23 weeks post injection. A second injection at 4 weeks markedly enhanced the antibody response and all EHV-1 gD-injected mice developed neutralizing antibodies. A lymphocyte proliferative response to whole EHV-1 was observed and a predominance of IgG2a antibodies after DNA injection was consistent with the generation of a type 1 helper T-cell (Th1) response. Following intranasal challenge with EHV-1, mice immunized with EHV-1 gD DNA were able to clear virus significantly more rapidly from lung tissue and showed reduced lung pathology, in comparison to control mice. PMID- 9987160 TI - Host immune responses to ribosome, ribosomal proteins, and RNA from Mycobacterium bovis bacille de Calmette-Guerin. AB - The ribosomes from BCG strongly induced delayed type hypersensitivity (DTH) skin reactions in guinea pigs immunized with live BCG or heat killed Mycobacterium tuberculosis H37Rv, and also induced lymphocyte proliferative response in mice immunized with ribosomes. In contrast, neither ribosomal proteins nor RNA alone induced both DTH skin reactions and lymphocyte proliferative responses. Particle form consisted of ribosomal proteins and RNAs might be absolutely required for the activation of immune responses. PMID- 9987161 TI - Modulation of mucosal and systemic immunity by intranasal interleukin 12 delivery. AB - Interleukin-12 (IL-12) is an important mediator of both cell-mediated and humoral immunity. We have now utilized a noninvasive intranasal (i.n.) delivery system to evaluate the ability of IL-12 to modulate both mucosal and systemic components of the immune system. Mice immunized i.n. with dinitrophenyl conjugated to ovalbumin (DNP-OVA) in combination with cholera toxin B subunit and IL-12 were found to have elevated levels of IFN-gamma and IL-10 mRNA transcripts in both lungs and spleens compared with mice not receiving IL-12. In addition, expression of lung IL-5 mRNA was inhibited. Analysis of bronchoalveolar lavage fluid after IL-12 treatment revealed a significant increase in IgG2a and unaltered IgG1 and IgA anti-OVA antibody levels. Serum IgG2a, IgG2b and IgG3 anti-DNP antibody levels were significantly increased by IL-12 given i.n., while serum IgG1 antibody levels were suppressed, results that are similar to those seen after systemic antigen plus IL-12 administration. Delivery of IL-12 i.n. also enhanced faecal IgG2a and suppressed IgA levels, in contrast to parenteral treatment which increased both faecal IgG2a and IgA antibody expression. These results provide evidence that i.n. IL-12 treatment can effectively modulate antigen-specific immune responses and enhance immunization strategies for mucosal vaccines. PMID- 9987162 TI - Protection against lethal Japanese encephalitis virus infection of mice by immunization with the highly attenuated MVA strain of vaccinia virus expressing JEV prM and E genes. AB - Genes encoding the glycosylated precursor of the membrane (prM) and envelope (E) proteins of a Korean strain of Japanese encephalitis virus (JEV) were inserted into the genome of the host-range restricted, highly attenuated, and safety tested MVA strain of vaccinia virus. MVA recombinants containing the JEV genes, under strong synthetic or modified H5 vaccinia virus promoters, were isolated. Synthesis of JEV prM and E proteins was detected by immunofluorescence microscopy, flow cytometry, and polyacrylamide gel electrophoresis. Mice inoculated and boosted by various routes with either of the MVA recombinants produced JEV neutralizing antibodies, that had titres comparable with those induced by an inactivated JEV vaccine, as well as haemagglutination-inhibiting antibodies. Mice immunized with 2 x 10(6) infectious units of MVA/JEV recombinants by intramuscular or intraperitoneal routes were completely protected against a 10(5) LD50 JEV challenge at 9 weeks of age. PMID- 9987163 TI - A chimeric protein comprised of bovine herpesvirus type 1 glycoprotein D and bovine interleukin-6 is secreted by yeast and possesses biological activities of both molecules. AB - Bovine herpesvirus type 1 (BHV-1) glycoprotein D (gD) engenders mucosal and systemic immunity and protects cattle from viral infection. Chimerization of cytokines with gD is being explored to confer intrinsic adjuvanticity on gD. Addition of the appropriate cytokine may convert gD into an antigen that specifically engenders protective mucosal immunity. Here DNA coding for the mature bovine interleukin-6 (IL-6) protein was fused through a synthetic glycine linker to the 3' end of DNA coding for the mature BHV-1 gD (tgD) external domain. It was cloned behind the yeast alpha prepro signal sequence and transfected into Pichia pastoris which secreted the chimeric protein (tgD-IL-6) as a 100 kDa molecule. This chimera combined the immunogenic properties of native gD and the in vitro biological activity of bovine IL-6 based on the following observations. A panel of BHV-1 gD-specific monoclonal antibodies recognizing five neutralizing epitopes on native gD reacted with tgD-IL-6. Sera from yeast tgD-IL-6-immunized mice neutralized BHV-1 infection in vitro. The chimeric protein enhanced total bovine immunoglobulin production 16-fold above tgD alone in pokeweed-stimulated bovine peripheral blood mononuclear cells (P < 0.05). This chimeric protein may be a potent mucosal immunogen. PMID- 9987164 TI - Exposure to yellow fever vaccine in early pregnancy. AB - We report on a data collection concerning exposure to yellow fever vaccine (YFV) during early pregnancy, ascertained through the European Network of Teratology Information Services (TISs) and the Pharmacovigilance Department of Pasteur Merieux Connaught (PMC). Six TISs had had no inquiry about YFV. Five submitted prospectively collected cases. Seventy-four cases were analyzed, 58 with a completed follow-up. Pregnancies ended in 46 births, five voluntary abortions and seven spontaneous abortions. Three newborns had minor anomalies and two had major defects (ureteral stenosis and triphalangeal hallux). Although the sample is too small to rule out a moderate increased risk of adverse reproductive effect of YFV, it gives no argument for such an effect and should lead to reassure pregnant women who might be inadvertently vaccinated. PMID- 9987165 TI - Prevalence of diphtheria toxin antibodies in human sera from a cross-section of the Italian population. AB - A polycentric study was carried out between 1993 and 1995 in order to evaluate diphtheria immunity on a representative sample of population from different areas of Italy. To determine diphtheria antitoxin, sera from 5187 apparently healthy subjects, divided according to sex and age groups, were titrated using an ELISA indirect method. A basic protective titre of diphtheria antitoxin (> 0.01 IU ml 1) was found in 4080 (78.6%) subjects. No statistically significant differences between males and females were observed. Our findings show that the proportion of susceptibles increases with age and a high proportion of adults no longer has diphtheria antitoxin at protective levels since toxigenic C. diphtheriae circulation is presently lacking in Italy. PMID- 9987166 TI - Immunoprophylaxis and immunotherapy against experimental visceral leishmaniasis. AB - The ability of the Leishmanial parasite, UR6 (MHOM/IN/1978/UR6) to act as a immunoprophylactic and immunotherapeutic agent against experimental visceral leishmaniasis in a hamster model was tested. The Leishmanial parasite, UR6, lacked LPG but possessed abundant message for kinetoplastid membrane protein-11 (KMP-11), and failed to induce visceral infection when given through the intracardiac route, unlike the virulent Leishmania donovani, AG83 (MHOM/IN/1983/AG83), the causative agent of Kala-azar. Priming of macrophage with UR6 in vitro, induced superoxide (O2-) generation whereas a similar experiment with virulent AG83 inhibited O2- generation. This observation prompted us to test the efficacy of UR6 as a immunoprophylactic and immunotherapeutic agent. It was observed that priming of hamsters with either live or sonicated UR6 in the absence of any adjuvant provided strong protection against subsequent virulent challenge. The UR6 mediated protection was also observed in hamsters having established infection. Furthermore, UR6 primed infected hamsters displayed a greatly extended life span as compared to infected hamsters. To our knowledge, this is the first report concerning the use of an atypical Leishmanial parasite, UR6 in immunoprophylaxis and immunotherapy in the absence of any adjuvant. PMID- 9987167 TI - Edward Jenner's Inquiry; a bicentenary analysis. AB - Edward Jenner's famous Inquiry was published 200 years ago. Probably few now know on what evidence he based his claims but most will be aware that they initiated controversy which to some extent still continues. This paper briefly reviews the Inquiry, analysing its merits and faults. Jenner's claims were based on slender experimental evidence and some of the information presented was incomplete and misleading. However Jenner's role in the introduction of vaccination was seminal and others could only test and extend his ideas. His reputation as the initial promoter of vaccination is justified. PMID- 9987168 TI - Mucosal vaccination with recombinant poxvirus vaccines protects ferrets against symptomatic CDV infection. AB - Canine distemper virus (CDV) infection of ferrets causes a disease characterized by fever, erythema, conjunctivitis and leukocytopenia, similar clinically to measles except for the fatal neurologic sequelae of CDV. We vaccinated juvenile ferrets twice at 4-week intervals by the intranasal or intraduodenal route with attenuated vaccinia (NYVAC) or canarypox virus (ALVAC) constructs containing the CDV hemagglutinin and fusion genes. Controls were vaccinated with the same vectors expressing rabies glycoprotein. Animals were challenged intranasally 4 weeks after the second vaccination with virulent CDV. Body weights, white blood cell (WBC) counts and temperatures were monitored and ferrets were observed daily for clinical signs of infection. WBCs were assayed for the presence of viral RNA by RT-PCR. Intranasally vaccinated animals survived challenge with no virologic or clinical evidence of infection. Vaccination by the intraduodenal route did not provide complete protection. All control animals developed typical distemper. Ferrets can be effectively protected against distemper by mucosal vaccination with poxvirus vaccines. PMID- 9987169 TI - Vaccine potential of a recombinant glutathione S-transferase cloned from Schistosoma haematobium in primates experimentally infected with an homologous challenge. AB - Patas monkeys were twice immunized with a Schistosoma haematobium-derived recombinant glutathione S-transferase (Sh28GST) then challenged with an homologous calibrated challenge. BCG and Freund's Complete Adjuvant (FCA) were used as adjuvants in two distinct protocols. Specific IgG and IgA antibody responses were intense and homogeneous in the animals receiving Sh28GST in the presence of FCA, whereas BCG could only induce moderate and heterogeneous antibody titres. No significant effect on worm burdens was evidenced 36 weeks post-infection in either group of Sh28GST-immunized animals compared to their matched controls receiving an irrelevant protein. Although not significant, 50% reductions in the numbers of eggs located in all tissues (FCA group) and in the urogenital system (BCG group) were noted. Moreover, the total number of excreted eggs was dramatically diminished by 60% and 77% in the BCG and FCA groups, respectively. These reductions reached 75% and 80% in the urines of vaccinated monkeys. Bladder pathology was also reduced in the animals displaying the lowest urinary egg excretions. There was no clear positive or negative correlate between antibody responses and individual levels of protection. Taken as a whole, our results show that Sh28GST was capable of significantly reducing S. haematobium worm fecundity in experimentally infected primates. Although FCA induced higher levels of protection, the efficacy of BCG as an adjuvant appeared sufficient to justify consideration of the future application of this new formulation as a vaccine against human urogenital schistosomosis. PMID- 9987170 TI - Urticaria following varicella vaccine associated with gelatin allergy. AB - An uncommon reaction to varicella vaccine has been urticaria. Based on two reports of urticaria believed to be due to gelatin in recipients of measles-mumps rubella vaccine, we suspected gelatin as the cause of generalized urticaria in two children after varicella vaccination. Intradermal testing with gelatin yielded a wheal and flare reaction in both children. We conclude that children known to be allergic to gelatin should not receive Oka/Merck varicella vaccine (VARIVAX). PMID- 9987171 TI - Human leukocyte antigens influence the immune response to a pre-S/S hepatitis B vaccine. AB - In this study we investigated the effects of a single pre-S/S (Hepagene) revaccination in a large population of multiple 'S' vaccinated anti-HBs antibody nonresponder individuals (< 3 IU/l). We investigate the influence of vaccine dose (5, 10, 20 and 40 micrograms/ml), number of previous 'S' containing vaccinations and the individuals HLA genotype on both B- and T-cell responses. We show that 76% of persistently nonresponder individuals produce anti-HBs antibody (> 3 IU/l) following a single revaccination with Hepagene. This anti-HBs antibody response was dose dependent. The group that received 5 micrograms/ml of Hepagene vaccine produced significantly less anti-HBs antibody than those receiving 10, 20 and 40 micrograms/ml doses (p < 0.05 in all cases). Individuals homozygous for HLA DRB1*0701; DQB1*0202 failed to produce > 100 IU/l of anti-HBs antibody, whereas, heterozygous individuals required > 10 micrograms/ml Hepagene vaccine. The T-cell responses to Hepagene were exclusive of the dose and magnitude of anti-HBs antibody responses. There was a trend towards increased stimulation indices in those individuals who received repeated 'S' containing vaccines. We have clearly shown that the immune response to Hepagene is influenced by the HLA genotype of the individual. However, further investigation is required to determine the specific role of these molecules in hepatitis B vaccine nonresponse. Hepagene is a registered trademark of Hedeva Pharma Ltd. PMID- 9987172 TI - Protection against anthrax toxin by vaccination with a DNA plasmid encoding anthrax protective antigen. AB - A DNA vaccine encoding the immunogenic and biologically active portion of anthrax protective antigen (PA) was constructed. Spleen cells from BALB/c mice immunized intramuscularly with this vaccine were stimulated to secrete IFN gamma and IL-4 when exposed to PA in vitro. Immunized mice also mounted a humoral immune response dominated by IgG1 anti-PA antibody production, the subclass previously shown to confer protection against anthrax toxin. A 1:100 dilution of serum from these animals protected cells in vitro against cytotoxic concentrations of PA. Moreover, 7/8 mice immunized three times with the PA DNA vaccine were protected against lethal challenge with a combination of anthrax protective antigen plus lethal factor. PMID- 9987173 TI - Effect of Mycobacterium sp. wall and Avridine on the antibody response, IgG isotype profile and proliferative response induced by foot and mouth disease virus (FMDV) vaccination in cattle. AB - Different immunomodulators have been previously tested in our laboratory as enhancers of the specific immune response to FMDV vaccines in a murine model [2 4]. Here, we present results of two of these immunomodulators, a water-soluble fraction of the cell wall of Mycobacterium sp. (WSF) and a synthetic lipoamide, Avridine (AV), which were tested in bovines included in FMDV oil vaccines. Two different concentrations of inactivated viral antigen were employed and the effect of different concentrations of the adjuvants were studied when added to the lower viral dose. It is shown that the inclusion of these adjuvants in the higher concentration in vaccines formulated with low antigen concentration induced the same antibody levels as those induced by vaccines containing twice the concentration of virus, and no adjuvants, and as a commercial formulation which performed with 100% of protection in the potency test. The IgG isotypes profiles induced in these experimental vaccines differed from those elicited by the commercial and control vaccines. Both IgG1 and IgG2 were augmented by the experimental formulations. These adjuvants, specially the WSF, also enhanced the cellular immune response against the FMDV in antigen driven proliferation assays, thus acting on a broad range of immune mechanisms. PMID- 9987174 TI - Immunogenicity of recombinant Escherichia coli expressing the omp31 gene of Brucella melitensis in BALB/c mice. AB - BALB/c mice were immunized with recombinant Escherichia coli expressing the omp31 gene of Brucella melitensis, a gene coding for a major outer membrane protein. Immunization resulted in the production of specific antibodies to B. melitensis in the serum, the production of which was considerably increased after boosting with a dose ten times lower than the first. A significant specific proliferative response of immune spleen cells to B. melitensis was observed 5 weeks after the first immunization but this response did not persist. Despite the induction of systemic humoral and cellular immune responses by recombinant E. coli expressing the B. melitensis omp31 gene, no significant protection against a challenge with smooth B. melitensis H38S was observed in immunized mice. These results demonstrate that despite the strong antibody response induced in mice, immunization with the recombinant Omp31 of B. melitensis does not confer any protective effect against a virulent smooth B. melitensis. However, its potential protective effect for protection against rough Brucella would be worth testing. PMID- 9987175 TI - Vaccination against the gastrointestinal nematode, Haemonchus contortus, using a purified larval surface antigen. AB - Sheep were immunized with a purified antigen (Hc-sL3) expressed on the surface of L3 larvae of the gastro-intestinal parasite, Haemonchus contortus, using different adjuvant and immunization routes. In the first experiment, intradermal immunization of sheep with Hc-sL3 and QuilA did not result in reductions in faecal egg counts after subsequent challenge infection while significant reductions were obtained when aluminium hydroxide (AH) was used as the adjuvant. Significant protection with Hc-sL3 absorbed on AH was confirmed in a second experiment and this protection was maintained when dextran sulphate was added to the Hc-sL3/AH mixture while the addition of pertussis toxin abrogated the protective effect. Significant levels of protection, as determined by reductions in both faecal egg counts and worm burdens, were also obtained when the Hc-sL3/AH mixture was injected into the rectal mucosa or the Hc-sL3 antigen was deposited on the surface of the rectal mucosa with cholera toxin. No correlations with antibody levels or isotype and protection were observed. PMID- 9987176 TI - Long-term follow-up of hepatitis A vaccination in children. AB - We conducted this follow-up study to evaluate the long-term immunogenicity of an inactivated hepatitis A vaccine in children. Ninety-six children who had seroconversion to antibody to HAV (anti-HAV) after receiving a three-dose schedule of inactivated hepatitis A vaccine were enrolled into this study. Sixty months after the initial vaccination, all vaccinees who received annual follow-up still had protective levels of anti-HAV. The geometric mean titer (GMT) of anti HAV, peaking at month 7 (4133 mIU/mL), kept declining throughout the follow-up period. The GMTs in months 12, 24, 36, 48 and 60 were 1722, 896, 896, 645 and 403 mIU/mL, respectively. Nine of the vaccinees were hepatitis B virus carriers. Their anti-HAV titers tended to be lower than those of the remaining vaccinees at all time-points, but the difference was not significant (p > 0.05). Natural booster was noted in one vaccinee during the follow-up period. In conclusion, inactivated hepatitis A vaccine is safe and immunogenic in children, the duration of protection against HAV infection is longer than five years. PMID- 9987177 TI - Priming of CD8+ CTL effector cells in mice by immunization with a stress protein influenza virus nucleoprotein fusion molecule. AB - Literature is accumulating which suggests the potential for stress proteins to form the basis of a novel vaccine technology. Immunization with mammalian tumor derived stress proteins and their associated peptides promote anti-tumor immunity. Vaccination with HIV-1 p24 antigen fused to mycobacterial heat shock protein (Hsp) Hsp71 enhances p24-specific immunity, as measured by p24-specific antibody production and in vitro cell proliferation and cytokine induction. An ovalbumin-Hsp71 fusion protein primes ovalbumin-specific CTL activity and resistance to challenge with an ovalbumin-expressing tumor. We have extended these observations by using a mycobacterial Hsp65 fusion molecule to prime CTL specific for a viral antigen. Gene fusion constructs were generated from DNA encoding Mycobacterium bovis strain BCG Hsp65 and individual fragments of influenza virus nucleoprotein (NP) encompassing H-2Kd- and H-2Db-restricted CTL epitopes. The ability of these purified recombinant fusion proteins to prime NP specific CTL was assessed in mice of appropriate H-2 haplotypes. We observed that adjuvant-free immunization with either fusion protein elicited significant CTL activity when administered at doses of 10-100 micrograms per mouse. An NP fusion protein made with glutathione-S-transferase failed to elicit NP-specific CTL, indicating that the phenomenon requires Hsp65 sequences. A single immunization with the Hsp65-NP fusion protein elicited CTL activity which persisted for a minimum of 4 months post-immunization, at which time it could be boosted by a second immunization. To our knowledge, this is the first report of a member of the Hsp60 family priming for antigen-specific CTL activity when employed as a fusion protein partner. PMID- 9987178 TI - Development and in vitro characterization of recombinant vaccinia viruses expressing bovine leukemia virus gp51 in combination with bovine IL4 or IL12. AB - Type 1 and type 2 immune responses are modulated by IL12 or IL4, respectively, at the time of lymphocyte priming. Importantly, type 1 responses have been associated with resistance to retroviral infection in mice, humans, and ruminants. Specifically, vaccination of sheep with vaccinia virus expressing bovine leukemia virus (BLV) gp51 resulted in protective immunity with the characteristics of a type 1 response, whereas vaccination of cattle resulted in a non-protective type 2 response. In order to test the hypothesis that cattle inoculated with BLV gp51 and IL12 will respond with a type 1 response, a recombinant vaccinia virus expressing BLV gp51 together with bovine IL12 was developed and characterized in vitro. For induction of type 2 responses a recombinant vaccinia virus expressing gp51 with bovine IL4 was similarly constructed and characterized. In this study recombinant cassettes were developed containing either the BLVenv gene alone or in combination with bovine IL4 or the two genes, p35 and p40, encoding bovine IL12. Correct alignment with p7.5 or p11 vaccinia promoters and orientation was confirmed by complete sequencing. Recombinant vaccinia viruses were generated by homologous recombination, selected based on large plaque formation due to reconstitution of the vp37 gene, and structurally confirmed by Southern blotting. Transcription of recombinant BLVenv, bovine IL4, p35 and p40 was demonstrated by RT-PCR. Expression of BLVenv gp51 protein and bovine IL4 was shown by immunofluorescence and immunoblotting. Biologically active bovine IL4 expressed by vaccinia virus stimulated lymphoblast proliferation, B lymphocyte proliferation in the presence of CD40L, and inhibited IFN gamma secretion from PHA activated PBMC in a dose dependent fashion. Finally, bovine IL12 expression and biological function was confirmed by dose dependent induction of IFN gamma secretion by PHA activated PBMC and the moderate enhancement of lymphoblast proliferation. In conclusion, bovine IL12 and IL4 expressed by recombinant vaccinia virus in vitro clearly exhibited type 1-type 2 modulating properties. PMID- 9987179 TI - Prophylaxis moving to centre stage. PMID- 9987180 TI - Report on a meeting of a working party sponsored by the European Commission to discuss the ethical, legal and social aspects of research on vaccines and vaccination (BIOMED2 BMH4 983 197). PMID- 9987181 TI - Characterization of the periodontal microflora by the fatty acid profile of the broth-grown microbial population. AB - The applicability of fatty acid analysis to the characterization of periodontal microflora was investigated using gas-liquid chromatography (GLC) and the software of the Sherlock Microbial Identification System (MIS) from MIDI Inc. Sulcus fluid was collected with paper points and anaerobically cultured in broth at 35 degrees C for four days. The broth-grown microbial population was extracted and the fatty acid methyl esters (FAME) were separated by GLC. The investigation of 67 specimens from asymptomatic sulci and of 32 specimens from inflamed sulci showed that the patterns of FAME profiles, the clustering of FAME profiles by computerized 2-D plot procedure, and the determination of the peak area index (PAI) of the FAME profiles differentiate between normal and pathological sulcus flora. Comparison of the clinical sulcus rating and the FAME data indicated that a pathological FAME profile may precede manifest periodontitis, and the normalization of the FAME profile may precede healing. It is concluded that the FAME analysis of sulcus fluid is a diagnostic aid for periodontological surveillance, for the initiation of preventive treatment of periodontitis, and for controlling the antimicrobial efficiency of therapeutic measures. PMID- 9987182 TI - Growth parameters of Borrelia burgdorferi sensu stricto at various temperatures. AB - Growth of Borrelia burgdorferi sensu stricto (prototype strain B-31) was studied in Barbour-Stoenner-Kelly BSK-H liquid medium, supplemented with 4.5% rabbit serum and antibiotics (phosphomycin, rifampicin), at various temperatures to early stationary growth phase. The number of cells was determined by darkfield microscopy. In the range of cultivation temperatures of 25 degrees C to 37 degrees C, generation time was between 8.26 and 12.36 h (the shortest one at 33 degrees C), and the specific growth rate between 0.056 and 0.083 h-1 (the highest one at 33 degrees C). The optimum growth temperature for B. burgdorferi was 33 degrees C, although good growth was also observed at 28 degrees C, 30 degrees C, 35 degrees C and 37 degrees C. The strain grew well but slowly at the temperature of 25 degrees C, whereas no growth was observed at 20 degrees C. PMID- 9987183 TI - Evaluation of three methods for culturing alginate throat swabs from cystic fibrosis patients. AB - Deep throat swabs are usually cultured for potential respiratory pathogens in patients with cystic fibrosis (CF) who do not produce sputum. Using alginate swabs, three methods were examined in the present study: (i) semiquantitative processing (direct plating); (ii) mere elution of swabs in Ringer's lactate followed by plating of the eluate; and (iii) complete quantitative processing (elution plus two-step dilution series). Throat swabs from 56 CF patients yielded 122 isolates of potential respiratory pathogens. Semiquantitative processing (n = 101 isolates) was not significantly inferior to elution (n = 104) and quantitative processing (n = 113; p > 0.05). Since semiquantitative processing is the simplest method, it is to be preferred, provided that alginate swabs are used. PMID- 9987184 TI - Phospholipase D-neutralization in serodiagnosis of Arcanobacterium haemolyticum and Corynebacterium pseudotuberculosis infections. AB - Phospholipase D (PLD) neutralization was used to examine sera of humans (n = 40) with a spontaneous infection by Arcanobacterium haemolyticum, sheep and goats (n = 76 and 79 respectively) with a spontaneous infection by Corynebacterium pseudotuberculosis, mice (n = 26) experimentally immunized with PLD from A. haemolyticum (PLD-A) and mice (n = 28) experimentally immunized with PLD from C. pseudotuberculosis (PLD-C). PLD-A and PLD-C were also used as neutralizing antigens. A positive result of neutralization was due to an inhibition of the haemolytic synergism with the equi factor from Rhodococcus equi. The titres of sera neutralizing the homologous PLD were always significantly higher than those neutralizing the heterologous PLD. The proportion of sera that were able to neutralize the homologous PLD in sheep, goats and mice immunized with PLD-A significantly exceeded the proportion of sera that neutralized the heterologous PLD. The antigenic properties of PLD-A and PLD-C were similar but not identical. PMID- 9987185 TI - Prevalence of Borrelia burgdorferi s.I. in Ixodes ricinus ticks from Styria (Austria) and species identification by PCR-RFLP analysis. AB - A total of 1163 I. ricinus ticks were collected in 3 different regions (15 localities) in Styria (Austria) in June 1997 and examined for the presence of spirochetes by dark field microscopy. The mean infection rate was 20.8%. Among 310 adults, 24.2% were positive and among 853 nymphs, 19.6% were positive. All 15 collection areas were shown to harbour infected nymphs with a positivity rate ranging from 5.8% (3/52) to 32.1% (18/56). Isolation attempts in BSKII medium resulted in 29 isolates. Species identification by PCR-RFLP analysis revealed 16 strains of B. garinii, 10 strains of B. afzelii and 2 strains of B. burgdorferi s. s. One isolate showed a mixed population of B. garinii and B. afzelii. In two collection areas, all three major Borrelia species were shown to be present in the tick population. PMID- 9987186 TI - Influence of growth conditions on expression of immunoglobulin G binding in group A streptococci. AB - Many group A streptococci (GAS) bind the Fc part of IgG. In the present work, the possible influence of growth time and incubation atmosphere on the expression of the IgG binding activity by GAS of various serotypes was studied. Among 13 GAS reference strains, two categories were distinguished on aerobic incubation at 37 degrees C, one expressing similar IgG binding activity at 6 h and 18 h (types M1, M4, M13, M15), and a second one which showed higher binding at 6 h than at 18 h (M9, M14, M22, M25, M48, M49). Only one strain (M36) bound less IgG at 6 h than at 18 h. Seven of the strains (M5, M6, M22, M25, M36, M48, M49) showed higher binding of IgG when grown in a 5% CO2 atmosphere than in air, whereas one strain (M14) showed a reverse pattern and in the remaining five strains, no influence was found. Protease activity was detected in the growth supernatant of most of the strains. For five selected strains, the time of appearance of supernatant protease activity coincided with a decay of surface IgG binding activity. Purified streptococcal cysteine protease was found to reduce or abolish the binding of IgG by each of three studied strains (M1, M13 and M15) and of type M1 or M15 purified IgG binding material. When tested in the stationary phase, a majority of 62 clinical GAS isolates belonging to 6 different M types showed high protease activity but low binding of IgG. We conclude that streptococcal IgG binding is often better expressed on growth in 5% CO2 atmosphere than in air. Furthermore, due to its sensitivity to streptococcal protease, the IgG binding activity is mostly higher during the logarithmic than during the stationary phase of growth. PMID- 9987187 TI - Problems of identification in clinical microbiology exemplified by pig bite wound infections. AB - Our experience from attempts to identify bacteria isolated from boar bite/gore wounds is the background for a discussion of identification problems. Some organisms, although not very common or well-known, can be identified when using commercial kits or conventional methods, provided they are sufficiently characterized, as exemplified by Pasteurella aerogenes isolated from cases 1 and 2. Some organisms may be wrongly identified, or not identified, by both commercial kits and conventional methods, unless seen by experienced microbiologists with knowledge of the original literature. This is exemplified by case 3, in which the final identification result was Bisgaard's taxon 15. Sometimes isolates cannot be identified even in reference laboratories and by using available identification tables and databases. In such cases, the organism involved may turn out to belong to a previously undescribed taxon. This is illustrated by the strains isolated from cases 4 and 5. PMID- 9987188 TI - Adhesion of Helicobacter pylori to yeast cells. AB - In order to get information as to whether direct interaction of H. pylori and yeasts may modulate the course of H. pylori infections, the adhesion of H. pylori to C. albicans, C. glabrata, C. guilliermondii, C. krusei, C. parapsilosis, C. tropicalis and S. cereviseae was investigated. H. pylori adhered significantly more frequently to C. tropicalis (adhesion ratio > 10%) than to the other yeasts (adhesion ratios < 5%). On an average, no significant difference to the adhesion ratios of E. coli and S. aureus was found. Electron microscopic examinations showed that H. pylori cells contacted the cells of C. tropicalis either by knob like structures or by close surface-to-surface adhesion. Cholesterol-depleted H. pylori cells adhered to the yeast no more than cholesterol-carrying cells. There was no indication that a direct cooperation with yeasts plays a role in H. pylori infections. PMID- 9987189 TI - Comparative in-vitro activities of trovafloxacin, ciproflaxacin, ofloxacin, and broad-spectrum beta-lactams against aerobe blood culture isolates. AB - The in vitro activity of trovafloxacin, a new fluoroquinolone, was compared with that of ciprofloxacin, ofloxacin, fleroxacin, ceftazidime, piperacillin/tazobactam, and meropenem against 613 consecutively recovered blood isolates from recently hospitalized patients. Susceptibility testing was performed by agar dilution according to NCCLS guidelines. Test strains included Acinetobacter species (n = 26), Escherichia coli (n = 137), Enterobacter species (n = 27), Klebsiella species (n = 42), Proteus species (n = 16), Pseudomonas aeruginosa (n = 28), Serratia marcescens (n = 13), Stenotrophomonas maltophilia (n = 7), enterococci (n = 54), coagulase-negative staphylococci (n = 38), Staphylococcus aureus (n = 137), Streptococcus pneumoniae (n = 27), beta haemolytic streptococci (n = 13), and viridans group streptococci (n = 48). The overall respective MICs at which 50% and 90% of isolates were inhibited (MIC50s and MIC90s) were as follows: trovafloxacin, 0.06 and 1 mg/l; ciprofloxacin, 0.25 and 4 mg/l; ofloxacin, 0.5 and 4 mg/l; fleroxacin, 0.5 and 16 mg/l; ceftazidime, 2 and 128 mg/l; piperacillin/tazobactam, 2 and 8 mg/l; meropenem, 0.06 and 4 mg/l. For the quinolones, the rank order of activity against gram-negative microorganisms was ciprofloxacin > trovafloxacin > ofloxacin = fleroxacin, against gram-positive organisms, trovafloxacin > ciprofloxacin = ofloxacin > fleroxacin. Data obtained showed the similar activity of trovafloxacin and ciprofloxacin against gram-negative pathogens and the superior activity of trovafloxacin against gram-positive bacteria thus making it a potential candidate for the empiric treatment of patients with suspected bacteremia and sepsis. PMID- 9987190 TI - Changes in serum sensitivity and hydrophobicity in a clinical isolate of Klebsiella pneumoniae treated with subinhibitory concentrations of aminoglycosides. AB - The effects of subinhibitory concentrations (sub-MICs) of gentamicin, netilmicin and amikacin on the serum sensitivity and the cell surface hydrophobicity of Klebsiella pneumoniae were investigated. At concentrations 1/16 or 1/8 of the MICs, in all antibiotics significantly enhanced the sensitivity of K. pneumoniae to human serum as compared to nontreated bacteria. The higher concentration of the antibiotics tested was more efficient. Survival of bacteria under these conditions ranged from 24.1% to 36.7% after incubation with 10% serum for 180 min when compared with the viability of the control bacteria. Bacteria grown with the test antibiotics at sub-MICs (1/8 or 1/4 of the MICs) manifested an effective decrease of the surface hydrophobicity. The aminoglycosides which were more effective at a concentration of 1/4 of the MICs reduced bacterial hydrophobicity to 28.5% (gentamicin), 14.8% (netilmicin) and 12.7% (amikacin) of the nontreated bacteria. PMID- 9987191 TI - Killing effects of antibiotics and two-fold antimicrobial combinations on proliferating and non growing staphylococci. AB - Antimicrobial agents are generally tested against bacteria in the log phase of multiplication to produce the maximal bactericidal effect. In case of foreign body infections, bacteria may multiply less optimally. We examined the effects of several classes of lipophilic antistaphylococcal agents to determine their antimicrobial activity towards coagulase-positive and coagulase-negative staphylococci during the non-growing and slowly growing phases. Only two-fold combinations containing rifampicin were bactericidal (3-log kill) against Staphylococcus aureus. This was in contrast to growing bacteria in the log phase, in which a variety of antibiotics produced relevant killing. Concerning the staphylococci examined, antibiotic killing was greatly dependent on the growth rate. Most of the two-fold combinations containing rifampicin showed additive and synergistic antibacterial activity both in growth and stationary states as measured by the killing kinetics. The theoretical and clinical implications of delayed killing by chemotherapeutic agents for established bacterial infections and infections involving foreign bodies are discussed. Antimicrobial combinations including rifampicin and a second lipophilic antistaphylococcal drug may be most promising and appropriate as coating substances for intravascular devices or for clinical application in cases of implant infections. PMID- 9987192 TI - Catheter-related infections in long-term catheterized dogs. Observations on pathogenesis, diagnostic methods, and antibiotic lock technique. AB - BACKGROUND: Intravascular catheters are associated with severe infections in patients, but only few reports on this problem in animal research exist. OBJECTIVE: We report on catheter-related bacterial colonization and its consequences in long-term catheterized animals. MATERIAL AND METHOD: Foxhounds were instrumented with intravascular catheters and flow probes to study the regulation of renal blood flow and pressures. RESULTS: After flushing the catheters, alterations in renal blood flow were observed and these could be related to bacterial colonization of intravascular catheters with Pseudomonas species. After attention had been focused on aseptic technique in all experimental phases and prophylactic antibiotic lock instituted, the occurrence of Pseudomonas bacteremia ceased, and the magnitude and incidence of catheter related colonization and infection by Pseudomonas species dropped considerably. CONCLUSION: The catheter-related colonization that occurred spontaneously in these animals resembled findings in animal experiments in which catheter-related infections were deliberately induced as well as observations made with regard to catheter-related infections in patients. This report emphasizes the importance of asepsis when working with animals with long-term intravascular catheters. We suggest that monitoring for this complication, e.g., by means of catheter cultures at the time of removal, should routinely be part of protocols for animal experiments using long-term intravascular catheters. PMID- 9987193 TI - Contact with ticks and awareness of tick-borne diseases among the Czech population--a pilot study. AB - In the Czech Republic, the incidence of Lyme borreliosis (LB) has shown a rising trend since 1988. The goal of this study has been to find out to what extent a selected part of population is aware of ticks and of the relationship between ticks and LB. The study was based on a questionnaire survey. A total of 110 respondents were selected, including 19 secondary school students, 32 blood donors, 44 park-goers, 15 countryside people. As many as 99% of the respondents were aware of the presence of ticks, 91% knew that ticks are sucking blood of humans and animals, 1.8% thought they eat leaves. 74.5% of the respondents expect ticks to reach them from the vegetation while 22% believe that ticks fall from the trees. Furthermore, 87% and 75% of the respondents indicated to have had ticks attached to the skin or to have removed a tick from other persons' skin, respectively. Only 6.7% of them had never come into contact with ticks. 17% of the respondents use disinfectant when removing a tick, while 67% use oil for tick removal. Almost 30% remove ticks with naked hands. Over 14% destroy the ticks by squashing them with naked fingers. Finally, about 11% of the population studied had never heard about LB and 41% were not aware of the risk of tick-borne encephalitis. PMID- 9987194 TI - Stabilization of dithranol in topical formulations. AB - The influence of different factors such as drug concentration, temperature, pH value, humidity, solubility and stabilizers on the antipsoriatic drug dithranol in topical formulations has been investigated. Dithranol was examined in lipophilic, hydrophilic and cream bases under defined conditions. Additionally, stabilizers have been investigated to protect dithranol against degradation. The drug stability in the formulations was measured by a selective HPLC system. The results showed a strong dependency of the degradation on the drug concentration. The influence of temperature is not of the same importance. Besides the pH value also the type of puffer system must be considerated. The most important effect on dithranol stability which has been directed is the solubility of the drug substance in the ointment base. With higher solubility a significantly accelerated degradation occurs. Degradations of dithranol in hydrophilic and lipophilic bases can be reduced by different stabilizers. Among others succinic acid and tartaric acid being most effective. PMID- 9987195 TI - Development of computerised procedures for the characterization of the tableting properties with eccentric machines. High precision displacement instrumentation for eccentric tablet machines. AB - The paper deals with the instrumentation of displacement on an eccentric machine. Two instrumentation variants are evaluated. A displacement instrumentation consisting of two transducers attached to the frame was corrected for a slight non-linear calibration curve and corrected for machine deformation. A powder height signal was calculated from both signals. Upon dynamic punch to punch compression the powder height signal showed an oscillation of +/- 17 microns in amplitude due to tilting of the upper punch holder. A newly developed direct powder height instrumentation consisting of a set of special punches and a special die was also corrected for nonlinearities and punch deformation. The signal was free from any tilting effects and its accuracy is in the order of magnitude of the surface roughness of the punches. The machine deformation is discussed in detail. The instrumentation of the frame of the eccentric press in terms of force is possible but less sensitive by a factor of 5.4 than the use of the force sensors. The total machine deformation reaches nearly 0.5 mm under maximum load which is more than is often expected. The deformation was found to be non-linear for about 2% of the total deformation, the remaining 98% are linear deformation. PMID- 9987196 TI - Effect of the substrate-binder interactions on the mechanical properties of compacts. AB - The effect of the substrate-binder interfacial interaction in granules, made of PVP and glass ballotini as model substrates, on the mechanical properties of rectangular compacts consisting of these granules was investigated by use of the four-point beam bending technique. The mechanical properties of the prepared compacts were correlated with the physico-chemical characteristics--contact angle, surface tension and binder concentration--of the granulation liquid. The mechanical strength and Young's modulus of the specimens both reached a maximum value when the binder concentration in the granulation liquid was increased to 20% (w/v) for all granulation liquid volumes used. Above a 20% PVP concentration, the increasing granulation liquid contact angle hindered the binder spreading, creating weak regions in the compact and decreasing its mechanical strength. PMID- 9987197 TI - The use of some hydrophobic substances in tablet technology. AB - The objective of this work is to continue in a study of utilization of synthetic triacylglycerides of higher aliphatic acids as additives improving the flow properties of granulates and reducing die friction in the tabletting press. These effects are not supposed to interfere with the drug liberation velocity. We have evaluated the effects of the synthetic triacylglycerides in theophylline containing model tablets using magnesium stearate as the reference standard. Magnesium stearate is the lubricant of choice in the production, found in up to 80% of all industrially produced tablets. PMID- 9987198 TI - [Investigations of drug release containing Cremophor emulsifiers]. AB - Release of poorly soluble drug from several creams containing 50-75% water was investigated and the dependence of liberation on the emulsifier- and water content was established. The emulsifier content vs. liberation function can be described with a maximum curve, the relationship between drug release and viscosity can be characterized by a reciprocal or a logarithmic function. PMID- 9987199 TI - [Interspecies allometric scaling in pharmacokinetics of drugs]. AB - Allometric scaling is an empirical examination of the relationships between the pharmacokinetic parameters and size (usually body weight, ratio of organ- and body weight, breathing number, etc.). Interspecies pharmacokinetics tend to approximate, the organism, as the sum of organs and tissues according to material balance. The allometric equations for the pharmacokinetic parameters were applied to scale the data with respect to pharmacokinetic time and remove the chronological time dependency. When the data of at least three species are available, the pharmacokinetic parameters can be fit according to body weight in log-log regression. Allometric scaling is not applicable in all cases, only when the selected species has similar physiological behaviour, such as protein binding, metabolism, etc. Valuable information for the evaluation of the effect and the biopharmaceutical characteristics may emerge from more creative data analysis based on all result collected during the preclinical evaluation of a new drug. Author examined the applicability of the interspecies scaling method in the case of a new drug depogen, using drotaverin as reference. The pharmacokinetic data were collected from mouse, rat and dog and during the evaluation human data were applied too. The usual pharmacokinetic parameters were determined (MRT, MAT, beta, etc.), the results of allometric analysis were collected and the standard deviation of measured and calculated values were given. PMID- 9987200 TI - Revised guidance to reduce risks to patients from health care workers exposed to HIV infection. PMID- 9987201 TI - Suspected viral haemorrhagic fever: rapid tests help to exclude dangerous infections. PMID- 9987202 TI - Obsessive-compulsive spectrum disorders. PMID- 9987203 TI - Disparities in drug development: the Japanese paradox. PMID- 9987204 TI - Obsessive-compulsive disorder in schizophrenia: epidemiologic and biologic overlap. AB - OBJECTIVE: To examine the co-existence of obsessive-compulsive disorder (OCD) with schizophrenia in terms of epidemiology and overlapping biologic substrates. METHODS: Review of the relevant literature. RESULTS: There appears to be a significant prevalence of OCD in schizophrenia--higher than what would be expected on the basis of calculated comorbidity figures. There is significant overlap in the proposed functional circuits of OCD and schizophrenia, which may lead to co-expression of symptoms. Although there is overlap in neurotransmitter dysfunction, the interactions are complex, especially in regard to the serotonin and dopamine systems. CONCLUSION: The expression of OCD in schizophrenia is complex but very intriguing. Theoretical hypotheses of the pathology of the 2 disorders now need to be tested in larger controlled trials. PMID- 9987206 TI - Treatment of bipolar mixed state with olanzapine. AB - OBJECTIVE: An open trial was conducted to determine the efficacy of olanzapine in the treatment of bipolar mixed state. PARTICIPANTS: Nine inpatients at a provincial psychiatric hospital who met the DSM-IV criteria for bipolar I disorder, most recent episode mixed. INTERVENTION: Olanzapine was added to the existing drug regime in patients who had failed to respond to adequate trials of mood stabilizers used alone or in combination with neuroleptics. OUTCOME MEASURES: Patients were administered the Clinical Global Impression (CGI) Scale, the Brief Psychiatric Rating Scale (BPRS) and the Global Assessment of Functioning (GAF) Scale before the initiation of olanzapine. These scales were repeated and patients were rated on the improvement subscale of the CGI at the time of discharge. RESULTS: Pretreatment means (and standard deviations [SD]) for the CGI scale, BPRS and GAF were 5.7 (1.1), 60.7 (13.7) and 17.8 (7.5), respectively. Post-treatment means and SD for the scales were 1.9 (0.6), 6.3 (3.3) and 71.7 (5.6), respectively. Paired t-tests on all measures indicated significant improvement in symptoms with t = 9.43, p < 0.001 for CGI; t = -13.28, p < 0.001 for BPRS; t = -21.83, p < 0.001 for GAF. The mean improvement subscale score of the CGI was 1.3 (SD 0.5) at discharge. CONCLUSIONS: Olanzapine was well tolerated and was effective in the acute treatment of bipolar mixed state. PMID- 9987205 TI - Regulation of corticosteroid receptor gene expression in depression and antidepressant action. AB - OBJECTIVE: Major alterations of the hypothalamic-pituitary-adrenocortical (HPA) system are often seen in patients with depression, and can be reversed by successful antidepressant therapy. Persuasive evidence points to the involvement of a dysfunctional glucocorticoid receptor system in these changes. The authors developed a transgenic mouse to determine the mechanism for these changes. DESIGN: In vivo and in vitro animal experiments. ANIMALS: Transgenic mice expressing glucocorticoid receptor antisense RNA and control mice. INTERVENTIONS: In vivo: hormone assays and dexamethasone suppression tests; in vitro: cell transfection, chloramphenicol acetyl transferase assay, Northern blot analysis, binding assays of cytosolic receptor. OUTCOME MEASURES: Indicators of depressive disorder in transgenic mice, effect of antidepressant therapy on dexamethasone binding in transgenic mouse hippocampus, mouse behaviour, and glucocorticoid receptor activity. RESULTS: Transgenic mice showed no suppression of corticosterone with a dose of 2 mg per 100 g body weight dexamethasone. Treatment with amitriptyline reduced levels of corticotropin and corticosterone, increased glucocorticoid receptor mRNA concentrations and glucocorticoid binding capacity of several brain areas, and reversed behavioural changes. In vitro experiments also showed that desipramine increased glucocorticoid receptor mRNA. CONCLUSION: These transgenic mice have numerous neuroendocrine characteristics of human depression as well as altered behaviour. Many of these neuroendocrinologic and behavioural characteristics are reversed by antidepressants. The antidepressant induced increase in glucocorticoid receptor activity may render the HPA axis more sensitive to glucocorticoid feedback. This new insight into antidepressant drug action suggests a novel approach to the development of new antidepressant drugs. PMID- 9987207 TI - Switching to moclobemide to reverse fluoxetine-induced sexual dysfunction in patients with depression. AB - OBJECTIVE: To determine the efficacy of substituting moclobemide, a reversible monoamine oxidase-A inhibitor, for fluoxetine to reverse fluoxetine-induced sexual dysfunction in patients with depression. DESIGN: Prospective open trial. SETTING: Outpatient treatment. PARTICIPANTS: Five patients with depressive disorder who experienced sexual side effects during treatment with standard doses of fluoxetine (20 to 40 mg per day). INTERVENTION: Discontinuation of fluoxetine and replacement with moclobemide (300 to 600 mg per day) after a 2-week washout period. OUTCOME MEASURES: Libido, orgasmic function (in women) or erectile and ejaculatory function (in men), and overall improvement in sexual function during a follow-up period of 2 months to 3 years. RESULTS: Among patients receiving fluoxetine questioned about sexual side effects, 4 (1 man and 3 women) had treatment-related diminished libido with poor orgasmic response or partial erectile failure, and 1 female patient had enhanced sexual desire with intense clitoral stimulation. In all patients, sexual disturbances resolved completely after a 2-week washout period and a switch to treatment with moclobemide. Moclobemide was well tolerated. The antidepressant effect of moclobemide was comparable to that of fluoxetine. CONCLUSIONS: Moclobemide may be preferred as a treatment for depression in patients with fluoxetine-induced sexual dysfunction. PMID- 9987208 TI - Severity gradation of the Montgomery Asberg Depression Rating Scale (MADRAS) in outpatients. PMID- 9987209 TI - Possible new mechanism for the antiparkinsonian effect of amantadine. PMID- 9987210 TI - [Trophic niches in calyptrate Diptera in Rio de Janeiro, RJ]. AB - Niche breadth and niche overlap of flies were estimated. The flies were breeding in different environments in Rio de Janerio (rural, urban and forest). It were used as a larvae substrate: banana mashed, mouse carcass, fish (sardine), bovine liver, shrimp and fresh human faeces. It were bred 14,294 flies, belonging to four families: Calliphoridae, Fanniidae, Muscidae and Sarcophagidae. The greater niche overlap values observed were: rural area: Phaenicia cuprina versus Chrysomya megacephala; urban area: Phaenicia eximia versus Sarcodexia innota and P. eximia versus Synthesiomyia nudiseta; forest area: P. eximia versus Hemilucilia flavifacies. The greater niche breadth recorded were: rural area: Peckia chrysostoma; urban area: S. nudiseta and Musca domestica; forest area: Euboettcheria collusor and P. eximia. PMID- 9987211 TI - Afrocentric perspective of adolescent pregnancy in African American families: a literature review. AB - This article gives a detailed overview of the literature on adolescent pregnancy in African American families. According to the latest data available from the National Center for Health Statistics (1998), the greatest decline in adolescent pregnancy was among African Americans. In spite of the decline of 21% from 1991 1996, African American adolescent's birth rate was still almost twice the rate of European Americans. The purpose of this paper was to provide information that may assist health care professionals or others interested in repeat adolescent pregnancy to more effectively provide care and/or to conduct research from an Afrocentric perspective. PMID- 9987212 TI - A comparison of sexual behavior and self-esteem in young adult females with positive and negative tests for sexually transmitted diseases. AB - Contracting sexually transmitted diseases is a serious health problem faced by young women, in part, because they may routinely engage in risky sexual behaviors. This study describes the sexual behaviors of eighty-one young adult females who had positive and negative tests for STDs. The STD-negative group consisted of forty-nine African American females and the STD-positive group was thirty African American and two Caucasian females. The women completed the Safe Sex Behavior Questionnaire and the Rosenberg Self Esteem Scale. Demographic factors were also examined. The findings revealed that STD-negative females had higher self esteem and practiced safe sex more frequently. Also, women with higher education and incomes above $10,000 a year, plus a higher self-esteem level scored higher on the SSBQ, indicating the practice of safer sex. Age was not related to self esteem or the practice of safe sexual behavior. Implications for nurse practitioner practice are discussed. PMID- 9987213 TI - The ABC's of black hair and skin care. AB - This paper identifies the physiological basis for hair and skin care of African American children and adults. Culturally specific terms are included to assist readers from other cultures to understand and communicate with African-American clients. In addition to describing various hair styles used by African-Americans, products that can assist with caring for black hair and skin are also discussed. Black and African-American are used interchangeably. PMID- 9987215 TI - Unknowing and knowing. PMID- 9987214 TI - Enhancing scholarship and community service in historically black colleges and universities. AB - A project designed to enhance scholarship and community service at Historically Black College and University nursing programs was conducted. The project outcomes and unique opportunities from these experiences are described. The discussion centers on how 2 schools and individual participants used their experiences to enhance their professional development, provide education and opportunities to minority student nurses, and participate in community service in predominantly African American communities. PMID- 9987216 TI - Dumb and dumber??? PMID- 9987217 TI - Suitability of patient education materials for cardiac catheterization. AB - Changes in healthcare delivery for such diagnostic procedures as cardiac catheterization have resulted in an emphasis on patient self-study, using booklets and videotapes given to them before the procedure. This transition mandates an evaluation of the appropriateness and effectiveness of these materials. The purpose of this study was to systematically assess the suitability of materials used to prepare patients for cardiac catheterization. Three videotapes and four booklets were evaluated using the Suitability Assessment of Materials instrument. Concrete objective information (procedural and sensation information) was also evaluated. Scores revealed only one video and two booklets suitable for patient education. None received a superior rating. These results suggest that some patient educational materials used to prepare patients for cardiac catheterization are unsuitable. Clinicians should augment current suitable materials to enhance their effectiveness. PMID- 9987218 TI - Outcomes of nursing care: how do we know? AB - Nurses have become increasingly interested and involved in the area of outcomes to assure that the patient is represented as more than a composite of physiological variables. The use of outcome measures has helped nurses articulate their unique value and contribution to the well being of patients. Nevertheless, many measures presently used to evaluate an outcome do not identify or acknowledge the unique contribution of nurses. Clinical nurse specialists and other advanced practice nurses must use their "ways of knowing" to develop appropriate measures and outcomes. Through this careful inquiry, nurses will then be equipped to ask "nurse-driven" questions regarding the development of appropriate outcomes and outcome measures and to analyze the models in which care is presently delivered. PMID- 9987219 TI - What can we do with the CNS-case manager dilemma? PMID- 9987220 TI - Psychiatric consultation-liaison nursing: revisiting the role. AB - With their special training and assessment skills, psychiatric consultation liaison nurses have a long history of making important contributions to patient care and staff development. This article reviews how psychiatric consultation liaison nurses have traditionally approached and implemented the nursing consultation process. Issues facing psychiatric consultation-liaison nurses are discussed. Opportunities such as focusing on subspecialization; expanding practice settings; dealing with organization-based, rather than patient-based mental health issues; and entering intra- and entrepreneurial practice are also explored. PMID- 9987221 TI - Enhancing communication by using the Coordinated Care Classification System. AB - Because of the changes in our healthcare system, some clinical nurse specialists (CNSs) are having to expand their traditional roles of clinician, educator, consultant, leader, and researcher to include case management activities. The CNSs at Promina Gwinnett Health System in Lawrenceville, Georgia, have combined CNS and case manager activities and have adopted the title "CNS/Outcomes Coordinator." The CNS/Outcomes Coordinator is responsible for coordinating patient care, promoting team collaboration, and facilitating communication. To inform the healthcare team of the CNS/Outcomes Coordinator's patient responsibilities, the CNS/Outcomes Coordinators developed a Coordinated Care Classification System. This article describes how coordinating patient care, promoting team collaboration, and facilitating communication can be enhanced by the use of a classification system. PMID- 9987222 TI - Collaboration: clinical nurse specialists can lead the way. PMID- 9987223 TI - Interdisciplinary collaboration. AB - This quasiexperimental study investigated interdisciplinary collaboration over a 16-month period on units using different collaborative practice strategies. Measures of collaboration and perceived physician involvement in collaborative practice were completed by 335 licensed staff members working on seven general adult units in an acute care hospital located in an academic medical center. Data were collected at two time points: in 1993 and 1995. A small but statistically significant decline in collaboration was found (p = 0.01) over the 16-month period. Analysis of variance revealed a significant difference (p = 0.03) in collaboration related to the method used to develop collaborative paths. Post hoc Tukey's test indicated that the presence of a case manager without collaborative paths did show higher levels of collaboration (p = 0.05). Regardless of the strategy used, perceived high physician involvement was related to greater collaboration than perceived low involvement with differences increasing over time (p = 0.02). These findings suggest the importance of perceived physician involvement in collaborative practice to interdisciplinary collaboration. PMID- 9987224 TI - Outcomes for better or worse. PMID- 9987225 TI - The advanced practice nurse and measuring outcomes of care. PMID- 9987227 TI - Aesthetic research: film. PMID- 9987226 TI - Sexual assault: the role of the advanced practice nurse in identifying and treating victims. AB - Sexual assault is the fastest growing crime in the United States with an estimate that one in four women will be sexually assaulted before she reaches 18 years of age. Nevertheless, only 1 in 10 rapes is reported to law enforcement authorities. Although victims face cross-generational and long-term physical, emotional, cognitive, sexual, and spiritual damage, they seldom share this history unless directly questioned by a clinician. This article reviews the rapidly growing body of literature on sexual assault and the negative health effects on female victims and their families. Sexual assault is defined, incidence is discussed, the aftermath is explored, and the roles of advanced practice nurses are examined. PMID- 9987228 TI - See how far we have come! PMID- 9987229 TI - Using forensic autopsies to teach advanced pathophysiology. AB - Forensic autopsies can be used to help teach advanced pathophysiology. Currently, most faculty use commercially available slides and overheads, but these are poor substitutes for actual tissue, organs, and systems. Student participation in cadaver dissections or observation of hospital autopsies may be preferable, but these options are not always available in many schools of nursing. The forensic autopsy, however, allows students to directly observe a variety of pathologies and their sequelae, while exploring the multiplicity of factors that contribute to a person's death. In addition, students enhance their physical assessment skills and learn forensic content that can be applied to nursing practice. Bringing such real-world experiences to lectures and student assignments encourages these adult learners to actively participate in the integration of pathophysiology theory with autopsy observations. PMID- 9987230 TI - The clinical nurse specialist as expert practitioner in the obstetrical/gynecological setting. AB - The role of the advanced practice nurse (APN) continues to evolve in specialty areas while healthcare systems seek solutions to issues of cost-containment, equity in access, and quality care. APNs have a significant role in facilitating the positive outcomes of clients utilized as measurable indicators in a managed care environment. The CNS as expert practitioner in the obstetrical/gynecological hospital setting integrates specialty knowledge and demonstrates specialty skills when working with childbearing and perimenopausal women and their families. Maintaining a holistic orientation to practice and keeping comprehensive documentation of activities facilitate achievement of quality outcomes for patients in this specialty field. Competencies essential to successful implementation of the expert practitioner role include: clinical expertise, effective communication skills, critical thinking and analytical skills, and a theoretical orientation to problem solving. The Roy Adaptation Model is an effective framework that can be used by the CNS in the obstetrical/gynecological hospital setting to promote, maintain, and restore health, as well as facilitate positive patient outcomes. PMID- 9987231 TI - Barriers to prescriptive practice for psychiatric/mental health clinical nurse specialists. AB - Prescriptive authority for advanced practice psychiatric nurses (APPNs) has recently been legislated in many states. APPNs in Minnesota were granted prescriptive authority in 1995, but from 1995 to 1996 only 17 of 80 qualified APPNs in that state had received prescriptive authority. A survey on the barriers encountered in obtaining prescriptive authority was mailed to the 80 APPNs who completed a psychopharmacology course required for prescriptive authority. Of the 54 (67.5%) APPNs who returned the questionnaire, 43 registered for the course for the purpose of prescriptive authority but only 17 of these respondents had received prescriptive authority. The major barriers to obtaining prescriptive authority reported by these APPNs were work setting limitations, personal comfort with prescribing, and ability to develop a collaborative agreement with a psychiatrist. Based on these APPNs' responses, suggestions are given for: increasing the acceptance of the prescriber role, developing support for the prescriber role, obtaining equitable reimbursement, and simplifying the process of obtaining prescriptive authority. PMID- 9987232 TI - A pivotal role for the CNS. PMID- 9987233 TI - Reducing readmission rates through discharge interventions. AB - Readmissions to the hospital account for a significant number of all hospital admissions. Early discharge and inadequate care both during and after hospitalization are among the causes cited. Increasingly complex care and an aging population mandate that clinical nurse specialists (CNSs) in acute care settings assume more pivotal roles in discharge planning and care. Discharge program and intervention models, and ways to incorporate discharge interventions into advanced practice in acute care hospitals, are discussed. In addition, the effectiveness of CNSs and their required qualifications are presented. PMID- 9987234 TI - The emperor and his clothes. PMID- 9987235 TI - The elderly type II diabetic: a treatment challenge. AB - Type II or noninsulin dependent diabetes mellitus is the predominant type of diabetes in the elderly. Complexities of diabetes management with elderly patients are discussed, including differences in presenting signs and symptoms of the disease, treatment complications that occur with concomitant illnesses or age related physiological changes, and drug interactions that can lead to either hypo or hyperglycemia. The goals of treatment are discussed. Standard therapies, including diet, exercise, and medications, are reviewed with the special considerations of the geriatric patient in mind. PMID- 9987237 TI - Assessment and management of eating and feeding difficulties for older people: a NICHE protocol. AB - Adequate nutritional intake is critical to preserving the health of older people. When an elderly person requires assistance with eating, the most social of all activities of daily living, the assessment of nutritional issues becomes multidimensional and interdisciplinary. Management strategies should involve the professional nurse's attention to dietary needs, as well as the social, cultural, and interactive components of mealtime. Additionally, special strategies need to be developed for people with cognitive and physical disabilities. PMID- 9987236 TI - Use of a content methodology process to enhance feeding abilities threatened by ideational apraxia in people with Alzheimer's-type dementia. AB - Self-feeding behavior is often the first of a chain of self-maintenance skills to deteriorate in people with Alzheimer's-type dementia and is a major determinant of institutionalization. Moreover, nurses working in geriatric settings report the feeding of patients as a most difficult management problem. Of the various features of Alzheimer's-type dementia that can affect a person's ability to feed him- or herself, ideational apraxia can explain the loss of ability to conceptualize, plan, and execute the complex sequence of motor actions involving the use of tools or objects necessary for feeding. In this article, a systematic process is used to review the research literature to develop substantive content for nurses caring for people with feeding problems related to ideational apraxia. Ideational apraxia is a condition in which an individual is unable to plan movement related to an object because he or she has lost the perception of the object's purpose. The specific abilities necessary for feeding that are threatened by ideational apraxia are identified. A tool to assess these abilities is described, and nursing interventions aimed at enhancing or preserving existing abilities, preventing excess disability, or compensating for lost abilities are presented. PMID- 9987239 TI - Keeping a watchful eye. Receipt of preventive service screening recommendations by women in long-term care facilities. AB - This study explored the extent to which women in long-term care facilities received preventive screening services. Physical examination screening of women residents exceeded the 40% recommendation of Healthy People 2000 with the exception of clinical breast examination and Pap smears. Laboratory and screening procedures--cholesterol, thyroid, and tuberculin testing--fell short of recommendations. Nurses in long-term care have an opportunity to enhance residents' quality of life by ensuring consistent use of preventive screening services. PMID- 9987238 TI - When death is near: helping families cope. AB - By using caring behaviors and recognizing the grief process, the nurse can help the dying patient and family gain emotional control, complete unfinished business, work through anticipatory grief, and learn how to let go. PMID- 9987240 TI - Patterns of nursing home referrals to consultant dietitians. AB - A survey was conducted to evaluate nursing home referrals to consultant dietitians of residents with nutrition-related concerns, the frequency of such referrals, and the timeliness of dietitians' responses. The results showed that, although residents with significant weight loss and pressure ulcers constituted a higher proportion of nutrition concerns referred to the dietitian, most referrals were made from a week to a month after the nutrition concern was identified. Residents with tube feedings or dysphagia concerns were more likely to be referred in a more timely manner, within 1 to 2 days. PMID- 9987241 TI - Physician's orders and nurses' notes. When time is pressing, details can be lost. PMID- 9987242 TI - A case study of nursing liability. Patient transfer from one facility to another. AB - Ongoing health care transitions include shorter hospital stays for elderly patients who need additional subacute care before they return to independent living. When continued care will be carried out in another facility, attentiveness to transfer details is essential to complete a safe and effective move. PMID- 9987243 TI - Keeping an eye on the hidden effects of eye drops. PMID- 9987244 TI - Don't forget the water! PMID- 9987246 TI - The dismantling of affirmative action. PMID- 9987245 TI - Infection control in the home: 1998 update. PMID- 9987247 TI - Are we reaching the healthcare consumer? AB - With the diversity of our communities and waiting rooms increasing, can we continue to justify the lack of diversity among healthcare professionals? This article reports the demographic composition of the U.S. and compares those data with the professional healthcare workforce. With a non-White population of nearly 25%, only 10% of RNs are non-White and about 12% of medical students are non White. Four reasons are presented for increasing diversity among healthcare professionals. These four include: improved culturally competent care, access to healthcare, healthcare outcomes and research, and provider access in high-need service areas. Healthcare organizations have gone on record as supporting increased diversity within high-skilled healthcare professions but without a commitment to increasing enrollments in professional healthcare programs, diversity goals will never be reached. PMID- 9987248 TI - Diversity in nursing: a challenge for the profession. AB - Affirmative action policies and programs have been in place since the 1960's to afford academic and job opportunities for women and minorities. The past few years have brought about debate and controversy over the benefits of affirmative action. In spite of affirmative action, minorities continue to be underrepresented in nursing. With the increase of minorities in the general population, nursing will be ill prepared to meet the challenge of providing care to a diverse society. One of the major reasons cited for an underrepresented minority population in nursing is the lack of recruitment and retention strategies. The answers are not in affirmative action alone, but from within nursing itself. PMID- 9987249 TI - Culturally diverse students enrolled in nursing: barriers influencing success. AB - Within the United States, the dominant culture is largely made up of Anglo Saxons whose values include the work ethic, thrift, success, independence, initiative, respect for others, privacy, cleanliness, youthfulness, attractive appearance, and a focus on the future (Spradley & Allender, 1996). For the last ten or more years, the number of international students enrolled in programs in health science within the U.S., including nursing, has increased more than 10% (Zikopoulos, 1990). Almost no data have been collected by schools of nursing on the difficulties they encounter while working with international students adjusting to and receiving an education in the U.S. (Colling & Liu, 1995). There are often many barriers that may influence culturally diverse and international students' success in nursing. These barriers may be environmental and located within the school of nursing or the college/university, or personal and student centered. The presence of appropriate support services on the college campus as well as within schools of nursing could enhance the success of culturally diverse students. Nursing and college/university faculty must become more aware of cultural difference in students and must use various strategies to retain these students. PMID- 9987250 TI - Experiences of ethnic minority faculty employed in predominantly white schools of nursing. AB - This qualitative study describes the bicultural experience of ten ethnic minority faculty employed in predominately white baccalaureate and higher degree nursing programs in the Southeastern section of the United States. Seven themes emerged from the data: (a) appraising, (b) proving, (c) fitting-in, (d) defending, (e) distancing, (f) being invisible, and (g) mentoring to describe their experience. Results also provided support for the authors' generated Bicultural Systems Model which evaluates why and to what extent a particular transaction or series of transactions between the person and the environment is perceived as stressful. The general perception among participants was that they were not fully accepted in the academic setting of predominately white nursing programs. As a result, some faculty were expending energy trying to convince others of their legitimacy; while others were choosing to distance themselves from the academic setting and white colleagues. This study indicates a need for dialogue between white and ethnic minority faculty to facilitate adoption of strategies that reduce the negative effects of the bicultural phenomenon. PMID- 9987251 TI - School preparation--it's not what it used to be!! PMID- 9987252 TI - Umbilical hernia, inguinal hernias, and hydroceles in children: diagnostic clues for optimal patient management. AB - The assessment of pediatric patients with a possible umbilical hernia, inguinal hernias, or hydroceles can often be problematic for the pediatric nurse practitioner. Understanding the embryologic processes related to these conditions may increase the diagnostic capabilities of the practitioner. Clues to assist in the differential diagnosis and current treatment modalities will be offered. Tips for parental guidance related to these conditions will enhance the team approach to effective referrals and optimal treatment of the children in this clinical population. PMID- 9987253 TI - Do the write thing: writing the clinically focused article. AB - Writing is both passion and pain. However, the pain can be easily modified with a better understanding of the writing process. With structure, a little know-how, and a lot of desire, eager nurse practitioners can soon write their first manuscript. The purpose of this article is to encourage pediatric nurse practitioners to write articles that pertain to their areas of clinical expertise. Examples are used to detail the writing process from idea formation to publication. PMID- 9987254 TI - Latex allergy: a relevant issue in the general pediatric population. AB - Although latex allergy is a widely recognized problem of the pediatric myelomeningocele population and of frequent users of latex products, it is often overlooked in the general pediatric population. The prevalence of latex in common household items and in medical environments increases one's exposure and thus one's possibility of sensitization to latex. Latex allergy may range from mild local reactions such as erythema to more severe systemic reactions such as asthma or anaphylaxis. The immunoglobulin E-mediated mechanism of these reactions has been confirmed serologically by the presence of latex-specific immunoglobulin E with radioallergosorbent testing. Because avoidance of latex is currently the only way to prevent reactions, the identification of household items that contain latex is extremely important. However, because inadvertent exposure to latex is not uncommon, Medic-Alert bracelets and an Epi-Pen should be provided for children allergic to latex. Pediatric nurses should consider latex allergy as a possible diagnosis in situations of unexplained allergic or anaphylactic reactions and should be aware of optimal therapeutic interventions. PMID- 9987255 TI - Intervention booster: adding a decision-making module to risk reduction and other health care programs for adolescents. AB - A generic adolescent intervention booster of the decision-making module, "Choices for Tomorrow: Decision Making as a Life Tool," is described for patient education. The intent of the intervention booster is refinement of adolescent decision-making skills by teaching a life tool for making lifestyle decisions (such as smoking and alcohol use) and other health-related decisions. An overview of the module is presented. The module includes a curriculum, a 17-minute life action videocassette, a participant's workbook, and two instruments to measure outcomes. The theoretical framework is based on the health/choice model, the Janis and Mann conflict model of decision making, and the Piagetian cognitive framework related to adolescent development. The decision-making module can be used alone or as a "booster" to supplement the content of new or existing intervention programs that are aimed at health promotion and maintenance during adolescence. Because the module was originally developed for adolescents who have survived cancer, a population that often experiences cognitive impairment from treatment, it includes cognitive remediation strategies (such as memory aids). The decision-making module can also be used in other learning situations with healthy or chronically ill adolescents and/or their parents. PMID- 9987256 TI - New strategies for the treatment of colic: modifying the parent/infant interaction. AB - INTRODUCTION: The purpose of this study was to validate the effectiveness of behavior modification in treating colicky infants. Colic was defined as a self limiting condition in infants less than 4 months of age with a complex of physical behaviors and inconsolable crying (> 2 hours a day for 3 days). It was hypothesized that when parents are given specific instructions about how to respond quickly and appropriately to their infant's cues (modification of the parent/infant interaction), the amount of crying by the infant decreases. METHOD: A quasi-experimental design with an untreated control group and a pretest and posttest was used for the study. Twenty-three infants were randomly assigned to intervention, nonintervention, and control groups. Crying diaries kept by the parents were used to obtain quantitative measurements of crying before and after intervention. The Nursing Child Assessment Feeding Scale (NCAFS) was used to measure parent/infant interaction. RESULTS: Crying was significantly reduced from 3.79 hours per day to 1.12 hours per day (F = 46.00, df = 2, P < .05) among infants whose parents received interventions of individualized counseling and education. Caregivers of colicky infants in the intervention group scored lower on the NCAFS (F = 5.59, df = 2, P < .05). CONCLUSIONS: Findings support previous research suggesting that crying can be reduced by modifying parental responses to the infant. PMID- 9987257 TI - Latex allergy: development of a resource manual. PMID- 9987258 TI - The young child with a hearing loss. PMID- 9987259 TI - Managing urinary tract infections in children. PMID- 9987260 TI - Respiratory distress and kidney failure in a 9-month-old infant. PMID- 9987261 TI - Children's health insurance program--an opportunity for improvement. PMID- 9987262 TI - Bringing an early pediatric literacy program to the clinic setting. PMID- 9987263 TI - The importance of being "nice". PMID- 9987264 TI - School health services and managed care: a unique partnership for child health. AB - The inevitable merging of the world of managed care and school health services, particularly nursing services, will allow both to benefit from the resulting collaboration. The inclusion of the school nurse in the continuum of health care delivery promotes effective, timely, accessible, cost-effective services for children. Managed care offers an opportunity to bring to prominence the role of the school nurse and to increase school-based health services. School health services staff must begin credentialing, data gathering, and quality improvement activities prior to entering negotiations with managed care organizations. Success of this partnership could result in improved access to health care for millions of underserved school-aged children, greater attention to preventive services, and an optimal setting for health promotion activities leading to improved health for all children. PMID- 9987265 TI - The School Health Intensity Rating Scale: establishing reliability for practice. AB - It is important for school nurses to identify health care needs and nursing resources necessary to achieve desired health outcomes for the school-age population. The purpose of this study was to determine interrater reliability for the School Health Intensity Rating Scale (SHIRS), a tool developed to assess intensity of health care needs of the school-age population. Four school nurses assessed 20 fictitious student records using SHIRS. The SHIRS produced moderate kappa coefficients for more than half of the 15 parameters with 2 additional parameters near the moderate kappa range. PMID- 9987266 TI - Research award winner: neurodevelopmental assessment of at-risk learners by school nurses and their tools of choice. AB - Deficits and delays in neurological maturation and development are closely related to academic difficulties. Early assessment and identification of children with such problems promote remediation and the prevention of secondary problems. The purpose of this study was to determine whether school nurses in a region of one Western state perform screenings for neurological deficits, and if so, which tools were used, how results were or could be used, and the school nurses' opinions of the Quick Neurological Screening Test (QNST). A descriptive study design was used and data were gathered using a questionnaire. It was found that school nurses do not routinely perform neurological screening on children at risk for learning disabilities. Reasons for non-use of neurological screening tools were: time constraints, role ambiguity regarding the appropriateness of neurological screening by nurses, and lack of knowledge of neurodevelopmental screening. Recommendations for addressing these issues and opportunities for further research are proposed. PMID- 9987267 TI - School nurse web authoring. AB - Many school nurses are now surfing the World Wide Web for clinical and professional information. The Web is also a tool for providing professional services and delivering nursing care. Three applications for school nursing are featured: using the Web for professional publishing, a state association web page, and a school nurse office website. PMID- 9987268 TI - A holistic approach to meeting students' needs: using hypnotherapy techniques to assist students in managing their health. AB - Nursing education has long been holistic in its approach to aiding the client or family. Further, most nurses, especially school nurses, are holistic by nature. That is, school nurses see a person as a whole being, physical, emotional, mental, and spiritual. The more conscious nurses become of their holistic nature and the more they expand their knowledge and skills in holistic methods, the more they can assist students and families in having greater control over their health. Examples of selected holistic techniques and their positive effects when used by students with diabetes and asthma are illustrated in case studies. PMID- 9987269 TI - Managing DNR requests in the school setting. AB - States and school districts are increasingly faced with the potential of Do Not Resuscitate (DNR) orders for students with serious medical conditions. School nurses should assume leadership in developing both policy and procedural protocols, in addition to implementing approved DNR orders in schools. This article presents the current status of DNR policies nationally, legal considerations, and the issues to determine when managing DNR orders at the school site. PMID- 9987270 TI - Gathering support. PMID- 9987271 TI - Using abbreviations correctly. PMID- 9987272 TI - Quick guide to vaccines. PMID- 9987274 TI - Myths & facts.... about alcohol abuse. PMID- 9987273 TI - Treating oversedation and respiratory depression. PMID- 9987275 TI - Placing a PICC tip properly. PMID- 9987276 TI - Teaching a patient with diabetes how to protect her feet. PMID- 9987277 TI - Actionstat: myasthenia gravis cholinergic crisis. PMID- 9987278 TI - Balancing act: keeping blood pH in equilibrium. PMID- 9987279 TI - Mounting an offense against lobar pneumonia. PMID- 9987280 TI - Till death do us part. PMID- 9987281 TI - Administering urokinase for catheter clearance. PMID- 9987282 TI - Guide to nursing organizations. PMID- 9987283 TI - Building bridges from barriers. PMID- 9987284 TI - The highs and lows of autoimmune thyroid disease. PMID- 9987285 TI - Winning at scholarships. PMID- 9987286 TI - Preventing drug interactions. PMID- 9987287 TI - Metoclopramide and akathisia. PMID- 9987288 TI - Dueling over a position. PMID- 9987289 TI - Home for the holidays. PMID- 9987290 TI - Assessing an external fistula. PMID- 9987291 TI - Myths & facts ... about fractures. PMID- 9987292 TI - Writing a narrative discharge summary. PMID- 9987293 TI - Administering a Z-track i.m. injection. PMID- 9987294 TI - Collagen hemostasis devices. PMID- 9987295 TI - Managing common pediatric emergencies. PMID- 9987296 TI - Taking charge in a geriatric emergency. PMID- 9987297 TI - Mr. Meier was a man of few words. PMID- 9987298 TI - Power in numbers: reducing your risk of bloodborne exposures. PMID- 9987299 TI - New drugs 99, Part 1. PMID- 9987300 TI - Teaching incentive spirometry. PMID- 9987301 TI - Handling criticism with dignity. PMID- 9987302 TI - Actionstat: myxedema coma. PMID- 9987303 TI - Ondansetron and headache. PMID- 9987304 TI - Metamorphosis. PMID- 9987305 TI - President's reflections. PMID- 9987306 TI - Issues, times, and work during my NANDA presidency. PMID- 9987307 TI - Joining the computer-based patient record world. PMID- 9987309 TI - Nursing diagnosis: assimilation of the concept in Canadian nursing. PMID- 9987308 TI - NANDA historical highlights. PMID- 9987310 TI - They still don't know. PMID- 9987311 TI - Utilization of a classification of nursing diagnoses. PMID- 9987313 TI - Physiologic nursing diagnosis: its role and place in nursing taxonomy. PMID- 9987312 TI - Historical perspective: the National Conference Group for Classification of Nursing Diagnoses (1978, 1980). PMID- 9987314 TI - The translation of NANDA taxonomy I into ICD code. PMID- 9987315 TI - Case study: care of the caregiver--family member with a chronic illness. PMID- 9987316 TI - Beyond knowledge deficit to a proposal for information-seeking behaviors. AB - TOPIC: Nursing assessment of knowledge of informational needs. PURPOSE: To present of a brief evolutionary analysis of knowledge deficit in terms of its significance, application, and use, and to present a proposal diagnosis, "information-seeking behaviors." SOURCES: Literature review of knowledge deficit and "information-seeking behaviors." CONCLUSIONS: Knowledge deficit is a nursing diagnosis that is significant for identifying a patient's need for education or knowledge. Its application has revealed limitations to validity and subsequent use. "Information-seeking behaviors" is proposed as an alternative diagnosis. Antecedents and defining characteristics are presented and areas for future research proposed. PMID- 9987317 TI - Powerlessness regarding health-service barriers: construction of an instrument. AB - PURPOSE: The purpose of the study was to develop a scale to calculate college students' powerlessness regarding health service barriers (PHSB). METHODS: Scale items were generated to represent two domains of interest: powerlessness and college students' powerlessness regarding health service barriers. The final 20 item instrument was subjected to multiple measures of validity with college students and panels of nurse experts in the area of nursing diagnosis. Reliability was assessed by two samples (n = 92 and n = 33) of college-age students. A final administration was conducted with 197 college students. FINDINGS: The PHSB scale was determined to be an accurate and consistent measure. CONCLUSIONS: This instrument will provide a reliable and valid measure to conduct research. PMID- 9987318 TI - Moving beyond content validation of nursing diagnoses. AB - TOPIC: Studies to establish construct and criterion-related validity of nursing diagnoses. PURPOSE: The overwhelming majority of previous studies addressed content validation by nurse experts. This paper describes strategies to move beyond content validation research to construct and criterion-related validation. SOURCES: The range of studies that should be conducted for development of nursing diagnoses are reviewed with examples drawn from the field of psychology. Existing studies on the diagnoses of ineffective breathing pattern, ineffective airway clearance and impaired gas exchange are used as examples. CONCLUSIONS: Many types of studies are needed for each nursing diagnosis. Increased funding and support for nursing diagnosis research will be facilitated by attention to the accuracy of nurses' diagnoses and outcomes of the diagnostic process. PMID- 9987319 TI - Marketing nursing in a nurse practitioner practice. PMID- 9987320 TI - The Center for Nursing Classification. PMID- 9987321 TI - Changing the face of corporate health care. PMID- 9987322 TI - Chronic illness management in the year 2005. AB - Nurses must study the future of chronic illness management so they can anticipate change and influence the direction it takes. The driving forces of change include social, technological, economic, political, and environmental factors. Pressure to provide value will require providers, insurers, and purchasers to cooperate and coordinate health care services. The preferable future of chronic illness management involves nurses functioning in the role of care coordinators in disease management. To achieve the preferable future the nursing community must communicate the ability of nurses to coordinate care, be involved in developing clinical practice guidelines, produce more highly educated nurse executives capable of assuming positions of power within the community, develop new models of care and new programs to facilitate change, form single service networks that can sub-contract with health plans, and prepare future advanced practice nurses in both the art of nursing and the business of caring. PMID- 9987323 TI - The triad of empowerment: leadership, environment, and professional traits. AB - Empowerment is defined as "moving decision making down to the lowest level where competent decisions can be made." In the hospital setting, this would most commonly be at the point of direct patient care or staff nurse level; however, this kind of empowerment requires an environment of autonomy where mutual trust and respect are encouraged. The empowerment process requires that staff be prepared to accept and effectively use expanded decision-making responsibilities. The professional accountabilities of the empowered nurse include having a sense of value about their work and willingness to provide the full scope of practice as well as ability to work as equal members of a comprehensive interdisciplinary team. In order to move into a fully empowered position, professional nurses need mentoring, education, awareness of political activism opportunities, and networking skills. PMID- 9987324 TI - Effects of hospital downsizing on surviving staff. AB - In 1993, 27% of 1,147 surveyed hospitals planned to decrease staff size in the next year. This study surveyed 48 vice presidents of nursing in North Carolina hospitals with an average inpatient census over 100 using a 13-item questionnaire in an effort to discover strategies that were helpful in effective downsizing endeavors. Of the 31 (48%) returned questionnaires, 11 (35%) of the VPs reported downsizing in the past 3 years, most of which required the closing of one or more units. The respondents ranked attrition as the most common strategy, followed by relocation, early retirement, a change in skill mix, and layoffs. The most important components in successful downsizing or reorganization efforts were: two way communication and sufficient planning, as well as seeking and using input from a broad group of staff (using both individual meetings and group forums/discussions). PMID- 9987325 TI - Determining cost drivers for pediatric home health services. AB - A variety of cost constraints threaten the financial viability of home health agencies. Thus, tools must be developed that expand the critical information resources that will be the key ingredient in successfully navigating the challenges in the volatile home health market. Identifying and analyzing the core processes with the pediatric home care team provided a template that could be used with other agency patient populations by producing cost trajectories based on anticipated care requirements and capturing information that could be used for both internal and external benchmarking. The cost drivers of key processes and activities must be known so that they can be controlled and appropriate rates for capitation contracts can be established. Activity-based management uses cost driver analysis, activity analysis and performance analysis, to determine strategies for redirecting the work processes and agency activities to achieve lasting cost reductions. PMID- 9987326 TI - Is it time to move on? PMID- 9987327 TI - Cost reduction: what a staff nurse can do. PMID- 9987328 TI - Specialty practice entrepreneur: the advanced practice nurse. AB - There are many opportunities in the health care arena to make a difference. The structured sense of change is "old school." New "surfers" of the system will be entrepreneurial in spirit, energy, and flexibility. There is no job description for the perfect person, only a sense of excitement and innovation that gives one the feeling energetic change is about to happen. In nursing, the risk takers are abundant in the APN role. It is the reason why they walk the line of provider/nurse. Making a difference to patients is important. Riding the waves of clinical care is the excitement. The final results are "the big waves" of life--a patient's life. A provider who defines the reality of practice creates a vision and skillfully bridges the road between the two. Design the surfboard--catch the wave. PMID- 9987329 TI - Setting the informatics standards: an overview of NIDSEC's information systems evaluation criteria. PMID- 9987330 TI - Micro-managing or leading: the clinician's challenge. AB - There are many reasons people micro-manage in leadership positions. Anyone who has moved into the ranks of leadership from a clinical position will experience the angst of having to adjust to a "hands off" style and to trust that working through others to get the job done will work. The first step is to recognize this tendency and to admit that it is perfectly natural for a clinician to have to make the transition from doing it alone to working through others. The next step is to take the time to surround yourself with people who are capable of becoming better at certain specialized areas than you are and then allowing them to work. And finally, it is important to always assess your ability to work through others effectively. One of the most demoralizing behaviors a leader can display is that of communicating distrust and lack of confidence by continually interfering with a person's ability to work effectively. PMID- 9987331 TI - Redefining the gold standard of health care AKA medical care. PMID- 9987332 TI - On target: a model to teach baccalaureate nursing students to apply critical thinking. AB - As nurses enter the 21st century, problem solving and critical thinking are critical to successful clinical practice. Studies have revealed that thought professionals may have critical thinking knowledge, they do not always use it in everyday practice. This article presents an education model that faculty members can use to teach baccalaureate nursing students to think critically and incorporate research findings into clinical practice. The model offers a four semester plan that can be integrated into programs of study. PMID- 9987333 TI - The devil is in the details: body fluid testing regulation and the erosion of nursing practice. AB - Nurses have long performed tests on simple body fluids (e.g., chem strip, urine Dip Stix, guaiac of stool, urine specific gravity). As a result of the interpretation of JCAHO regulations by hospital administrators, nurses no longer have access to the supplies necessary to perform these tests. This article discusses the background surrounding the issues of body fluid regulation and how the current JCAHO laboratory regulations erode the scope of nursing practice. The author makes specific suggestions for nurses to retain their practice in this area. PMID- 9987334 TI - Invest in yourself. Lessons learned from nurse entrepreneurs. PMID- 9987335 TI - Said another way. Is the ADN graduate prepared to practice in community settings? AB - The downsizing and closing of acute care facilities and the movement to community based healthcare services are decreasing the need for RNs in acute care facilities. In the past, the associate-degree nurse (ADN) has filled the majority of positions in acute care. With the trend to provide health services in community setting, will the ADN be prepared for positions in community facilities? ADN educators must reevaluate how they are educating students for practice. The author reviews the 1995 recommendations from the Pew Health Professions Commission and relevant current directives from the National League for Nursing. PMID- 9987337 TI - Health care's best value. PMID- 9987336 TI - The emerging health occupations. 1968. PMID- 9987338 TI - Strategic planning for postacute care. AB - The author examines workable approaches and benefits of using strategic planning to prepare for future postacute care. PMID- 9987339 TI - Medicare imposes new caps on postacute care. AB - Prospective payment systems are replacing the methods Medicare uses to reimburse home health agencies, skilled nursing facilities, and rehabilitation hospitals, as well as imposing new limits on payments for outpatient rehabilitation services. Medicare stands to save substantial sums of money and possibly to hasten the formation of integrated delivery systems for postacute care. PMID- 9987340 TI - Legal risks in long-term care. AB - Although traditional liability principles apply in alternative settings, the application can change to accommodate the differing standards of care in long-ter care facilities. PMID- 9987341 TI - Questions & answers from the JCAHO. What's new for 1999? Part III. AB - The final part in this series outlines important changes to the JCAHO's performance improvement standards. PMID- 9987342 TI - A few points about point-of-care technology. AB - Managed care's focus on patient-centered care has made the need for point-of-care (POC) clinical systems more critical than ever. This article examines some of the more common POC options available, explains what nurses need to know to choose among them, and suggests ways to ensure that nursing's needs are addressed in the selection process. PMID- 9987343 TI - Partners in quality. AB - A university system counters funding cutbacks for nursing education by partnering with a hospital system. The partnership benefits both institutions. PMID- 9987344 TI - Change ... ouch! AB - Through change workshops, nurses can manage their emotions experienced during restructuring, such as losing familiarity, becoming insecure in their jobs, and grieving the loss of coworkers. The workshops focused on three themes: reminiscence, survival, and celebration. PMID- 9987345 TI - Cut training costs with computer-based tutorials. AB - New clinical information systems use client-server software applications that require knowledge of personal computers, Microsoft Windows, and mouse control. Here, the authors describe a low-cost training method to supplement classroom teaching. PMID- 9987346 TI - How to avoid age bias. AB - Data from the Department of Health and Human Services reveal that the nurse population is aging. To balance values and economic imperatives, nurse managers must be aware of the ethical dimensions when managing the older employee. PMID- 9987347 TI - Ease your management workload and develop staff. AB - A community hospital created a program where staff nurses work as house supervisors. The plan improves house supervisor coverage and provides opportunity for nursing staff development. PMID- 9987348 TI - LTC directors of nursing define educational needs. AB - Do nursing programs prepare directors of nursing in long-term-care facilities? This study examines their roles, academic and career goals, and their educational needs and preferences. PMID- 9987349 TI - Closing the distance. AB - Geriatric technicians work in the field, providing a link between care providers and rural elderly patients. In this study, the new role enhanced patient outcomes and satisfaction. PMID- 9987350 TI - Stress relief for critical care nurses. AB - Critical care nurses' stress levels have increased due to patient-focused care models that supplement staffing with unlicensed assistive personnel. Stat nurse programs can alleviate nurses' anxiety by providing short-term professional critical care assistance without disrupting structured health care models. PMID- 9987351 TI - What five regulatory trends mean to nursing practice. AB - Officials from the National Council of State Boards of Nursing report how developments in key areas will affect nursing practice. PMID- 9987352 TI - Decentralizing unit coordinator services. AB - Restructuring unit coordinator/unit clerk services by decentralizing this staff and having them report directly to nurse managers can totally integrate them into the functions and activities of a patient-centered team. This article describes how nurse managers can evaluate the feasibility of decentralizing unit coordinators in their own institutions. PMID- 9987353 TI - Infusion devices require educated users. AB - With increased use of intravenous therapy, nurse managers can use this guide to select and integrate appropriate equipment and educate staff. PMID- 9987354 TI - Taming your anger. Use these strategies to soothe the savage beast. PMID- 9987355 TI - Bedside nurses: realistic research competencies. PMID- 9987356 TI - CHES: committed to education. PMID- 9987357 TI - Ask AONE's experts ... about identifying nurse-specific cardiac outcomes. AB - Here, three nurse executives suggest how to identify nurse-specific outcomes indicators for the cardiac setting. PMID- 9987358 TI - Signposts for the next century. PMID- 9987359 TI - Long-distance nursing kindles multistate licensure debate. AB - Telehealth enables nurses to practice across state lines, but it also raises the critical issue of multistate licensure. This article explores nurses involvement in telehealth and the multistate licensure discussion--key issues, developments, players, and models currently being considered by states. PMID- 9987360 TI - New transfer rule encourages acute care partnerships. AB - To prepare for the Transfer Rule's financial impact, nurse leaders should understand these issues, ramifications, and strategies. PMID- 9987361 TI - Target high-risk areas for medication errors. AB - Medication errors are recently a more frequent basis for successful malpractice cases against nurses. Here, the author provides case examples and high-risk trends. PMID- 9987362 TI - Managed care may crunch GME programs. AB - Can teaching hospitals continue operating graduate medical education programs in a world of cost-conscious purchasers, competitive marketplaces, and cutbacks in Medicare's financial support? The absence of widely evident financial problems may slow efforts to establish national trust funds for graduate medical education. PMID- 9987363 TI - How does the JCAHO define new restraint standards? AB - The Joint Commission's restraint standards draw differences between restraint and behavior management and outline special circumstances for hospital-based long term care. PMID- 9987365 TI - Help for home health strategies. AB - Although home health care clearly isn't an industry for the weak-hearted, a sound strategic plan increases your chances for survival. These eight concepts can help nurse managers plan a multifaceted approach. PMID- 9987364 TI - Fiscally "fit" in a managed care system. AB - As Americans and their employers demand a more cost-effective, coordinated system of health care that achieves good clinical outcomes, managed care is transforming professional nursing. Here's help in understanding how to keep nursing fiscally "fit". PMID- 9987366 TI - Educate ICU assistive personnel. AB - Many institutions use assistive personnel in intensive care units (ICUs) to provide more cost-effective nursing care. One ICU uses a comprehensive, competency-based orientation program to help fulfill the assistive personnel's unique orientation needs. PMID- 9987367 TI - 10 trends for the new year. AB - Nurse managers can expect their new year's agenda to include issues related to span of control, Y2K compliance, recruitment and retention activities, and more. PMID- 9987368 TI - Can I talk to a nurse? AB - Nurses need education to go from bedside to "phoneside" nursing at the growing number of call centers. The authors tell how to build technical and procedural skills, a preparative knowledge base, and nurses' confidence. PMID- 9987369 TI - Climbing higher. AB - A New York hospital builds a more equitable clinical ladder system to include nurse managers, clinical nurse specialists, nurse practitioners, and nurse midwives. The system defines the nurses' roles and specific performance criteria. PMID- 9987371 TI - Does your staff take orders by phone? PMID- 9987372 TI - Managed care perspective: survey of hospital professionals. PMID- 9987370 TI - Latex-allergic patients: operating room considerations. AB - With the potential for intraoperative reactions, it's imperative that operating room nurse managers are informed and prepared to handle latex-allergic patients. PMID- 9987373 TI - Keeping track of technology transfers. AB - Nurse managers can assess and control the influx of new technologies in their units and educate staff by understanding technology development history. PMID- 9987375 TI - From enemies to friends: nurses and computers unite. PMID- 9987374 TI - Ask AONE's experts ... about fulfilling the nurse's role in billing compliance. AB - Here, two nurse executives suggest how to identify nurse-specific outcomes indicators for the cardiac setting. PMID- 9987376 TI - What strategies can help us sensibly manage patient information? AB - Here, the JCAHO answers questions about managing information--security, confidentiality of medical records, and the completion of operative reports. PMID- 9987377 TI - No dumping: ED transfer risk. AB - The Emergency Medical Treatment and Active Labor Act (EMTALA) outlines how hospitals must screen, treat, and transfer emergency department patients- regardless of their ability to pay. PMID- 9987378 TI - Tech talk on multistate licensure. AB - Professional nursing associations, unions, state regulatory boards, and even Congress are hotly debating the topic of multistate licensure. This article discusses several hurdles to implementing a multistate licensure model and explains how technology can help to overcome them. PMID- 9987379 TI - Medicare increases managed care's accountability, Part 1. AB - This year marks the beginning of Medicare's Quality Improvement System for Managed Care (QISMC), a tool that monitors the quality of care that managed health plans give their Medicare and Medicaid members. QISMC, which requires health plans to demonstrate improvements in the quality of care, will increase health plans' administrative costs without increasing capitation rates. PMID- 9987380 TI - Learning that lasts for times that change. Staff of Nursing Management. PMID- 9987381 TI - Negotiation strategies for men and women. AB - The ability to negotiate plays a key role in one's professional and personal life. If men and women want to negotiate successfully, they must know the steps of negotiation plus the sex differences when approaching the negotiation process. PMID- 9987382 TI - Build institutional commitment to improving pain management. AB - In 1997, the University of Wisconsin began working collaboratively with the Joint Commission on the Accreditation of Healthcare Organizations (JCAHO) to integrate pain assessment and treatment into the JCAHO standards and accreditation processes. Pain care committees are an effective mechanism for implementing these changes. The authors discuss the critical role nurse managers can play in the development and success of these committees' activities. PMID- 9987383 TI - The leader in you. AB - A practice-based theory of nursing leadership, the Integrated Leadership Practice Model, promotes job satisfaction and motivates staff to participate in activities that will produce quality customer outcomes. The author lists applications for nurse leaders. PMID- 9987384 TI - Want simple, superior resource management? AB - Many nurse managers practice enterprise-wide resource management across networked departments and facilities. Here's help in understanding how automation can ease the process. PMID- 9987385 TI - Y2K compliance countdown. AB - The new century brings unique challenges--especially Y2K compliance. This article presents nurse managers and executives with an overview of the issues and action steps to keep their organizations on track. PMID- 9987386 TI - Stop the carts. AB - Nurses and pharmacists at the University of Utah Hospitals & Clinics successfully implement an automated medication distribution system to cut costs, and find they also create measurable process improvements. PMID- 9987387 TI - Tracking patients, tracking costs. AB - Some 18.5% of hospitals employ a nurse case manager in the emergency department (ED) to decrease unnecessary hospital admissions, and address insurance company concerns about excessive ED visits. Consultants expect this management trend to increase. PMID- 9987388 TI - 11 easy ways to build rapport. PMID- 9987389 TI - Patient call system provides efficient delegation. PMID- 9987390 TI - Take the plunge: expanding the float pool to "closed" units. PMID- 9987391 TI - Pointed strategies for needlestick prevention. AB - Engineering, behavioral, and organizational changes can help nurse managers reduce or eliminate needlestick injuries on their units. PMID- 9987392 TI - Ask AONE's experts ... about implementing a case management program. AB - Here, two nurse executives explain how to work with administrators and physicians to implement a case management program. PMID- 9987393 TI - The second installment of the 1998 pay increase. PMID- 9987395 TI - To be or not CV? PMID- 9987394 TI - The real cost of nurse shortages. PMID- 9987396 TI - Dear Mr. Blair.... PMID- 9987397 TI - Doing it our way. Interview by Frances Pickersgill. PMID- 9987398 TI - Health screening. PMID- 9987399 TI - Homing instinct. Interview by Jenny Knight. PMID- 9987400 TI - Desperately seeking health care. PMID- 9987401 TI - Get ready for e-mail. PMID- 9987402 TI - Medical Research Council: a new initiative. AB - The Medical Research Council recently announced a research initiative concentrating on disabling disorders of older people using multidisciplinary approaches. Here, we explain what the initiative will mean. PMID- 9987403 TI - Pneumothorax. AB - This article discusses different types of pneumothorax and aspects of management, including physiotherapy and the insertion and removal of chest drains. PMID- 9987404 TI - Community education: a portfolio approach. AB - The NHS Executive (NHSE) is encouraging the use of occupational standards in nurse education programmes. This article outlines the use of occupational standards in developing an assessment of competence strategy for students taking a specialist community nursing degree. PMID- 9987405 TI - Obsessive compulsive disorder: nature and treatment. AB - This article discusses the characteristics of people with obsessive compulsive disorder (OCD), their assessment, treatment and the increasing importance of self help. PMID- 9987406 TI - Nothing to declare. PMID- 9987407 TI - When your character comes into question. PMID- 9987408 TI - Don't attack me--I'm a student nurse. PMID- 9987409 TI - A time for connection is a time for healing. PMID- 9987410 TI - A meaningful health assessment course for baccalaureate nursing students. AB - In response to the challenge of teaching health assessment to large groups of entry-level BSN students with minimal experience in the health professions and a faculty belief that theory and practice are best actualized with small groups, a new health assessment course was implemented. Based on a philosophy of student accountability and self-direction in learning, faculty willingness to try new teaching strategies, and using computer testing, a successful course was developed. Students rotated through specific small group clinical labs while preparing with textbooks, study questions, videotapes, and computer-assisted instruction. Evaluation methods based on case application and the use of computer testing technology were implemented for this course. The result was increased satisfaction for the faculty and the students with enhanced application experiences supportive of the clinical practice. PMID- 9987411 TI - Spirituality and prayer: a new age paradigm for ethics. PMID- 9987412 TI - Elder caregivers: their challenges trials, and triumphs. AB - The growing percentage of Americans who are elderly and the prevalence of chronic medical conditions will soon necessitate an expanded system of home health care. Presently, the financial and physical burden of this care falls on the elder and the family. This article discusses the issues surrounding elder caregiving. PMID- 9987413 TI - Nurses as writers. AB - Although nurses are expected to be competent in on-the-job writing, most nurses receive little formal education in the types of writing required in practice. Thus, it is important for faculty in schools of nursing to include in the curricula various types of writing assignments to help students develop these skills. This article describes how at one university a course, "Nurses as Writers," provides opportunities for students to learn and practice the types of writing needed in their professional careers. PMID- 9987414 TI - Substance abuse in rural women. AB - Substance abuse is a significant problem for millions of women. Until recently, however, most research focused on urban men. As a result, there are significant gaps in our knowledge of substance abuse in women, especially in rural settings. This descriptive study examines risk factors for substance abuse among a small sample of rural women who are in treatment for substance abuse. The MAST and CES D were used for initial screening for alcoholism and depression. The NIMH Diagnostic Interview Schedule and Research Diagnostic Criteria were used to establish diagnoses of alcohol and drug abuse and comorbid disorders. Risk factors examined included family history, victimization, stressful life events, alcohol expectancies, and coping. Implications of findings for nursing assessment and intervention are discussed. PMID- 9987416 TI - The players weigh in. PMID- 9987415 TI - Factors associated with penile amputation in Thailand. AB - This report describes factors associated with the act of penile amputation by three female partners in southern Thailand. While gender-specific roles and paternalistic behaviors are normative in Thai society, specific precipitating factors for the three amputations included: (1) an immediate financial crisis that adversely affected one of the children in the family; (2) ingestion of drugs or alcohol by the husband immediately before the event; (3) public humiliation of the wife in the presence of a mia noi (secondary wife) or concubine within the week that preceded the incident. Understanding women's cultural preservation in Thailand may promote culturally sensitive and meaningful nursing care. PMID- 9987417 TI - Inspired by what we see on TV. PMID- 9987418 TI - Prevention of infective endocarditis in the pediatric congenital heart population. AB - In 1997, the American Heart Association updated recommendations for the prevention of sub-acute bacterial endocarditis (SBE) or infective endocarditis (IE) occurring in the pediatric population with congenital heart disease (Dajani, et al., 1997). Although uncommon, endocarditis remains an important cause of morbidity and mortality in children with cardiovascular disease, which constitutes the primary population at risk. Through comprehensive discharge planning and teaching, the advanced practice nurse (APN) and the pediatric cardiovascular nurse may contribute significantly toward preventing IE in this population. Nursing's role and responsibility is to convey the appropriate information to patients, families, and the staff who care for children with heart disease. PMID- 9987419 TI - Caring for children awaiting heart transplantation: psychosocial implications. AB - Heart transplantation presents an extremely stressful life transition for pediatric recipients and their families. The waiting period of the preoperative stage has been described as the most stressful aspect of the process. The stress and coping model of Lazarus and Folkman (1984) can be used as a conceptual framework for addressing stressors of pediatric transplant patients and their families. A case study of a preadolescent child awaiting heart transplantation in a hospital outside of a transplant center highlights common concerns, including feelings of isolation, depression, boredom, hopelessness, helplessness, exhaustion, lack of privacy, financial burdens, role strain, and family disruption. Psychosocial needs can be assessed and met, using a multidisciplinary approach. Because the preoperative stage can be stressful for nurses as well, the case study also explores the struggles of unit nurses trying to coordinate and manage the patient's care. PMID- 9987420 TI - Retention and use of cardiopulmonary resuscitation skills in parents of infants at risk for cardiopulmonary arrest. AB - Policies of most neonatal intensive care units include teaching cardiopulmonary resuscitation (CPR) to parents or other caretakers prior to infant hospital discharge. However, little is known about CPR skills retention in this population or the outcome of parents' use of CPR. This is a study to measure CPR skills 6 months following CPR training to identify characteristics predicting successful performance and to determine if parents used CPR. A sample of 100 parents or related caretakers of infants at risk for an out-of-hospital respiratory or cardiac arrest 6 months following CPR training were asked to demonstrate CPR on an infant mannequin and 94 agreed to participate. Although they were excluded from the study if they had a CPR course within the past 2 years, 37% had taken CPR sometime in the past. Only one third of participants (n = 31, 33%) were able to perform satisfactory CPR. Those who demonstrated satisfactory CPR skills were more likely to have had previous CPR training and to have experienced higher levels of social support at the time of training than those who achieved unsatisfactory CPR performance ratings (p < .05). A logistic regression analysis revealed previous CPR training, social support, and level of anxiety at time of CPR training to be the most important predictors of CPR skills retention. Seven parents reported using CPR to resuscitate their infant who had suffered a respiratory arrest. All seven were successful. CPR skills decay is significant for caregivers of infants at high risk for cardiopulmonary arrest. Parents should be encouraged to review the steps of CPR frequently and to attend refresher classes. A significant proportion of parents of infants hospitalized in the neonatal intensive care unit are called upon to use CPR and are able to use it appropriately. PMID- 9987421 TI - Insertion of indwelling urethral catheters in infants and children: a survey of current nursing practice. AB - The purpose of this study was to identify current nursing practice standards for the insertion of indwelling urethral catheters in infants and children. A comparative descriptive design was used to survey a sample of 46 children's hospitals to determine recommended practice guidelines for size, type of catheter, insertion length, and source of nursing policies. Findings revealed a wide variation in practice often without a clear scientific or research base. In the absence of nursing research and established standards, it is essential that nurses base their practice decisions on an understanding of anatomical structure of the urethra and bladder and on knowledge of the dimensions of available catheters. PMID- 9987422 TI - The effects of a breastfeeding campaign on adolescent Korean women. AB - A sample of 412 Korean adolescent female students were surveyed to determine their attitudes, norms, and intentions toward breastfeeding. Before completing the survey, 207 of the students were exposed to a breastfeeding campaign. A panel presentation and a video stressed the importance and advantages of breastfeeding and presented breastfeeding as a positive experience for mothers. Students exposed to the campaign showed positive attitudes and norms toward breastfeeding and indicated their intent to breastfeed. The control group of 205 students who were not exposed to the campaign showed more positive attitudes and norms toward bottlefeeding and indicated their intent to bottlefeed rather than to breastfeed. Accordingly, a breastfeeding campaign can contribute to promoting positive attitudes and norms toward breastfeeding and to the positive intentions to choose breastfeeding. PMID- 9987423 TI - The child with traumatic brain injury returns to school. AB - Traumatic brain injury (TBI) continues to be the leading cause of acquired disability in childhood (Lazar & Menaldino, 1995). As children with TBI return to home and schools, primary care clinicians and educators who often lack information about their long term abilities to function are encountering them more frequently. This article describes the pathophysiology of pediatric TBI and difficulties that can be encountered when the child returns to school and offers suggestions for nurses who can assist the child in receiving appropriate educational services. PMID- 9987424 TI - An ethical dilemma: who should know and who should tell. AB - According to the International Code for Nurses "The nurse holds in confidence personal information and uses judgment in sharing this information" (Guido, 1997, p. 390). Disclosing information involves using judgment. Who should know and who should tell the children when the parent is terminally ill is the focus of this family case study. PMID- 9987425 TI - A dilemma within the family: commentary on who should know and who should tell. AB - Dilemmas for nurses may reflect a conflict between values and the choices a patient and family may make. When the debate involves the young children of a dying family member, who decides what is best for the children and how does the conflict get resolved? Rarely are the solutions simple. Following professional principle is imperative. Respecting the perspective of the dying often requires a set of fine balancing strategies: those of the professional and those of the family. PMID- 9987426 TI - Pediatric management problems. Developmental delay due to environmental factors. PMID- 9987427 TI - Inhaled tobramycin (TOBI). AB - Inhaled tobramycin was recently approved by the FDA in a 300 mg formulation for inhalation. The new product, manufactured by PathoGenesis Corporation, is referred to as TOBI and is indicated for cystic fibrosis patients with Pseudomonas aeruginosa. The advantage of high dose inhaled tobramycin is a greater concentration of the drug delivered to bacteria in the lung with potentially reduced oto- and nephrotoxicity. PMID- 9987428 TI - Families in pediatric critical care: the best option. AB - Parental visitation in pediatric intensive care units, induction rooms, and postanesthesia care units is still limited despite the incongruence of such policies with existing stress and social-support theories. As recently as 1994, a survey of 125 randomly selected hospitals in 10 southeastern states found that 57% restricted visits to pediatric patients in intensive care units to brief periods, 5 to 15 times per day (Whitis, 1994). Little justification can be found for these practices. Infection rates have not been found to increase with initiation of 24-hour visitation by family members and support persons. The positive emotional impact of parental presence during a child's hospitalization has been documented for both parents and children. To bring about changes to permit and support open visitation, several things are necessary. First, an understanding of the historical context of visitation policies is important. Second, efforts to dispel concerns are needed, including staff preparation. Third, a philosophical switch to family-centered care must be adopted. PMID- 9987429 TI - Children's Defense Fund focuses Congress on child care: both sides of the aisle submit proposals. PMID- 9987430 TI - PC savvy. A little maintenance goes a long way. PMID- 9987431 TI - Ethics in action. Whistle blowing. PMID- 9987432 TI - Ethics on the job. A survey. Quality vs. cost. AB - In this third installment in our series, nurses tell us how hospital cost-cutting measures have taken a bite out of quality of care, affecting everything from staffing levels to patient discharge to the availability of supplies. Depending on where you work, though, the news isn't all bad. PMID- 9987433 TI - Trauma! Chest injuries. AB - Chest trauma can range from broken ribs and knife wounds to collapsed lungs and bruised hearts. This detailed discussion of mechanism of injury, assessment findings, and treatment strategies will help you identify problems and increase your patients' chances for a quick and successful recovery. PMID- 9987434 TI - Bullets: damage by design. AB - The seemingly random devastation caused by bullets can be better understood--and predicted--by knowing how they're designed and how they act after entering the body. PMID- 9987435 TI - A case study in care. AB - Home care nursing isn't just changing dressings, checking blood pressure, or even giving i.v. therapy. It's providing a critical interface between the patient, the health system, and the patient's family. This story provides a compelling example. PMID- 9987436 TI - Cut the risks for cardiac cath patients. AB - As the list of interventions performed with the aid of femoral catheterization grows, so does the number of patients at risk for developing post-procedure problems. Here's a primer on how to recognize and prevent complications like pseudoaneurysm, arteriovenous fistulas, and retroperitoneal hematoma. PMID- 9987437 TI - Abstinence is not the only answer. PMID- 9987438 TI - Why I became a nurse.... PMID- 9987439 TI - The legal implications of latex allergy. PMID- 9987440 TI - What's causing this chest pain? PMID- 9987441 TI - Computers or cytotechnologists? PMID- 9987442 TI - Who should decide how effective cervical cancer screening will be? PMID- 9987443 TI - Automation of primary screening for cervical cancer. Sooner or later? PMID- 9987444 TI - Determining the utility and effectiveness of the NeoPath AutoPap 300 QC System used routinely. AB - OBJECTIVE: To evaluate routine use of the NeoPath AutoPap 300 QC System (AP 300) as it influences diagnostic quality and operations in a large cytology laboratory. STUDY DESIGN: During a three-month period, 35,143 conventionally prepared consecutive cervical cytologic smears taken from non-high-risk women and evaluated as negative by our staff of 25 cytotechnologists were selected for processing by four AP 300 instruments. Slides flagged for review by the AP 300 were reevaluated by our five quality control (QC) cytotechnologists. False negative (FN) results were compared with results of our current practice (CP), random-selection QC method, used during the preceding six months. RESULTS: A 240% increase was seen in the FN detection rate for atypical squamous cells of undetermined significance (ASCUS) and squamous intraepithelial lesions (SIL) (n AP = 65 FN in 5,034 QC, n CP = 77 FN in 22,052 QC) and a 744% increase in the FN detection rate for low and high grade SIL (n AP = 24 FN/5,034 QC, n CP = 12 FN/22,052 QC). The rate of overcall by cytotechnologists did not increase. The QC ASCUS/SIL ratio improved. FN biopsy correlation increased from 45% to 85% (n CP = 17/38 agreement, n AP = 23/27 agreement). Turnaround time increased by one or more days for negative and 1.5 days for QC result reporting. Sensitivity varied among instruments. CONCLUSION: More FN results and greater specificity were seen using the AP 300 than using CP. As with other instrumentation, each laboratory should establish acceptable ranges of performance and baseline values for sensitivity and specificity. PMID- 9987445 TI - Does use of the AutoPap assisted primary screener improve cytologic diagnosis? AB - OBJECTIVE: To correlate the ranked review slides by the AutoPap Assisted Primary Screener with the final cytologic diagnosis and to assess whether the ranking of slides improves diagnostic accuracy. STUDY DESIGN: A total of 5,865 consecutive conventional and suitable cervical/vaginal smears, including high-risk (HR) cases, were processed by the AutoPap System. All slides designated Review were manually screened by two cytotechnologists using the Ranked Review Report. All abnormal findings and reactive/reparative changes were referred to two attending cytopathologists for a final diagnosis. After screening, the Review slides called Within Normal Limits (WNL) were selected according to rank for a further Quality Control (QC) review by the supervisor. All HR cases not selected by AutoPap for QC review were also rescreened. The final diagnoses of the possibly abnormal/reactive/reparative referred slides were recorded and distributed in five ranks according to the Ranked Review Report assignment. RESULTS: Of 5,865 slides, 5,120 (87%) qualified for scanning. The AutoPap System designated 3,840 (75%) slides for manual review. One thousand three hundred forty-five slides were assigned for QC review. After elimination of nonqualified slides, 763 remained. Rescreening detected 1 high grade squamous intraepithelial lesion (HSIL), 2 low grade squamous intraepithelial lesions (LSIL), 5 atypical squamous cells of undetermined significance (ASCUS) and 5 Benign Reactive Changes (BRC). QC of 364 HR cases revealed 1 LSIL, 2 ASCUS and 3 BRC. Ultimately, 313 (8.1%) smears were diagnosed as ASCUS or a more severe abnormality, 262 (6.8%) as reactive/reparative changes, 3,259 (84.8%) as WNL and 6 (0.1%) as unsatisfactory. Of 313 abnormal slides, 181 were ranked by the system in the 1st rank, 61 in the 2nd, 38 in the 3rd, 19 in the 4th and 14 in the 5th. No HSIL or more severe lesions occurred in the fourth and fifth ranks. CONCLUSION: Our study validated the claim by the manufacturer that a significant epithelial abnormality is more likely to be present if a high score is assigned to a slide. The preliminary results support use of the AutoPap Assisted Primary Screener to improve cytologic diagnosis. PMID- 9987446 TI - Performance of the AutoPap primary screening system at Jefferson University Hospital. AB - OBJECTIVE: To evaluate the performance of the AutoPap System for primary screening of cervical/vaginal cytologic smears at the 25% no review rate at Jefferson University Hospital. STUDY DESIGN: A total of 5,865 consecutive conventional and suitable cervical/vaginal smears, including high-risk cases, were processed by the AutoPap System. Slides designated "no further review" (NFR) were manually screened by a cytopathologist (rapid screening) and a cytotechnologist (detailed screening) to detect epithelial abnormalities and assess the slide adequacy. The presence of Candida or Trichomonas was noted. Three cytopathologists determined the final diagnosis of all epithelial abnormalities by majority agreement. RESULTS: Of 5,865 slides, 5,120 (87%) qualified for scanning. The system classified 1,280 slides as NFR (25%) and 3,840 (75%) as review. Manual screening of 1,280 slides classified as NFR revealed 1,252 cases within normal limits, 10 atypical squamous cells of undetermined significance (4, favor low grade squamous intraepithelial lesion, 6 favor reactive) and 18 benign cellular changes. Adequacy assessment discrepancies were detected on 98 (19%) of 515 cases of satisfactory but limited by lack of endocervical component (SBLBLEC) and 15 (14%) of 105 cases on satisfactory but limited by inflammation/obscuration. Twenty-five percent of cases classified as SBLBLEC were vaginal smears. Trichomonas vaginalis was noted in 12 slides and Candida in 29. CONCLUSION: These preliminary results show that in our patient population, the AutoPap primary screener selected as NFR mostly slides within normal limits. The adequacy assessment discrepancies were comparable to those found in routine laboratory practice. PMID- 9987447 TI - PAPNET for cervical cytology screening. Experience in Greece. AB - OBJECTIVE: To validate the efficacy of PAPNET for cervical cytology screening. STUDY DESIGN: From a total of 50,000 gynecologic cases we selected 24 primarily negative smears from patients who, during follow-up, developed a precancerous lesion or cancer in a short time, ranging from a few months to two years. These negative smears were rescreened by the PAPNET automated system and reevaluated by two observers. A third observer blindly reevaluated the same cases manually. RESULTS: Reevaluation after PAPNET screening showed one false negative smear, for a rate comparable to that of manual reevaluation, which also reclassified the same case. The time required to interpret a smear using the PAPNET system was approximately one minute, while the time required for conventional manual screening was approximately five. CONCLUSION: PAPNET is an efficient and fast screener for the detection of precancerous cervical lesions and cancer. PMID- 9987448 TI - Multicenter comparison of manual and automated screening of AutoCyte gynecologic preparations. AB - OBJECTIVE: To compare AutoCyte SCREEN-assisted evaluation of AutoCyte PREP liquid based preparations with manual microscopic screening of the same preparations in a masked, multisite trial. STUDY DESIGN: AutoCyte PREPs were made using the CytoRich automated, liquidbased method from the residual cellular material on the collection device after a conventional cervical smear had been made. The study involved 1,676 samples collected sequentially from high-risk patients at two medical centers. The AutoCyte PREPs were then screened manually by cytotechnologists at one of two laboratory sites. All abnormal slides were reviewed by the site pathologists for final diagnosis. The PREPs were then remasked and screened using the AutoCyte SCREEN automated, interactive screening system, designed to select potentially abnormal slides for manual review while allowing the direct sign-out of negative slides. The AutoCyte SCREEN-assisted practice result was determined by combining the interactive SCREEN result with manual evaluation for those cases selected by SCREEN for manual review. All slides deemed abnormal were manually reviewed by an independent reference pathologist. The original manual review results were then compared to the AutoCyte SCREEN-assisted practice results stratified by the Bethesda categories of abnormal diagnoses as determined by the reference pathologist. RESULTS: Of the 1,676 cases, 494 were determined to be abnormal (ASCUS+) by one or both of the study methods and also by the independent reference pathologist. Of these 494 abnormal cases, 312 had a reference diagnosis of LSIL+, and 139 had a reference diagnosis of HSIL or cancer. The remainder of these cases were ASCUS or AGUS. Sensitivities and false negative proportions were stratified by the reference pathologist based on Bethesda categories as "truth" and compared. For LSIL+ cases, manual screening alone had a sensitivity of 89% as compared to 98% for the AutoCyte SCREEN-assisted practice. Manual screening demonstrated 90% sensitivity to HSIL or greater abnormality as compared to 99% sensitivity by the AutoCyte SCREEN-assisted practice. CONCLUSION: There was a concurrent significant reduction in the false negative fraction using the AutoCyte SCREEN as part of screening practice. Specificity for both screening practices was equivalent. PMID- 9987449 TI - Utility of residual AutoCyte cervical cytology samples for image analysis. AB - OBJECTIVE: To ascertain the utility of residual liquid-preserved cervical cytology samples for DNA profiling studies. STUDY DESIGN: Ninety-nine liquid preserved cervical cytology samples from a high-risk population were received two months after the initial diagnosis at another laboratory. Each residual sample was processed to yield one Papanicolaou-stained and one Feulgen-thionin-stained slide. The former were examined manually without knowledge of the submitted findings and were also examined on the AutoCyte SCREEN interactive system. DNA profiling of > 185 cells per case was performed on an RPW image analyzer. Results were compared with submitted diagnoses. RESULTS: The 99 cases included 59 normals, 9 ASCUS/AGCUS, 16 HSIL, 12 carcinomas and 3 unsatisfactory. Interlaboratory agreement between residual and initial samples was good (unweighted kappa = .609). Abnormals were characterized by 2C deviation indices > 2.0 and 5C exceeding rates > 4.37%. AutoCyte SCREEN system examination of residual slides of high grade abnormalities was 100% sensitive and 40% specific. CONCLUSION: Residual AutoCyte cervical cytology samples are stable and yield reproducible results for routine and ancillary studies of cervical cytologic abnormalities. The AutoCyte SCREEN system was 100% sensitive for high grade abnormalities in this enriched sample, even when operating on residual material. PMID- 9987450 TI - Semiautomated monolayer preparation of bronchial secretions using AutoCyte PREP. AB - OBJECTIVE: Development of a method for semiautomated preparation of purified, representative and conventionally stained monolayer smears from bronchial secretions suitable for subjective and/or automated cytodiagnosis. STUDY DESIGN: Bronchial secretions from 50 patients with and 48 without carcinoma cells of different types were collected in Saccomanno's fixative. After routine pick-and smear processing, residual material was subjected to a mucolytic agent (ammonium thioglycolate). Separation of cells was performed by differential centrifugation through aqueous sucrose. The pellet was automatically processed by the AutoCyte PREP system. RESULTS: Slides revealed well-preserved, slightly shrunken, homogeneously distributed cells devoid of mucus, cellular debris and bacteria in monolayer arrangement nearly without overlap. Granulocytes were eliminated to a large extent. Comparison with pick-and-smear specimens showed more tumor cells per square centimeter of slide surface in 100% of AutoCyte PREP slides. The number of tumor cells per AutoCyte PREP slide was higher in 46% and lower in 54%. Selecting slides at random and requiring at least 10 abnormal cells to establish a tumor diagnosis were achieved in 82.7% if only one, in 88.0% if two and 94.0% if seven or eight AutoCyte PREP slides were investigated. CONCLUSION: The semiautomated method yielded conventionally stained, purified monolayer smears from bronchial secretions with cellular morphology suitable for evaluation by cytologists and screening machines. Representativity of AutoCyte PREP monolayers was superior to that of pick-and-smear slides. PMID- 9987451 TI - AutoCyte Interactive Screening System. Experience at a university hospital cytology laboratory. AB - OBJECTIVE: To evaluate the AutoCyte Interactive Screening System (AutoCyte Screen) as a prescreener for the cytologic detection of cervicovaginal abnormalities. STUDY DESIGN: Eight hundred fifty-six AutoCyte Preparation System from cervicovaginal samples were evaluated by AutoCyte-Screen. AutoCyte-Screen displayed 120 cell images and 6 low-power images for review by the cytotechnologist. The cytotechnologist classified the case as WNL, abnormal or unsatisfactory. AutoCyte-Screen then revealed its classification as either unsatisfactory, WNL, abnormal or undecided. These classifications were combined to form an interactive result that was compared to the diagnosis from previous manual review. RESULTS: Interactive results were as follows: 251 (29.3%) abnormal, 581 (67.9%) WNL and 24 (2.8%) unsatisfactory. The abnormal interactive result contained 15 ASCUS/AGUS and 25 SILs; the WNL interactive result contained 5 ASCUS/AGUS and 2 SILs. No ASCUS/AGUS or SILs were in the unsatisfactory interactive category. The false negative proportion was 10.5% for the interactive diagnostic method vs. 15.7% for manual review for LSIL. CONCLUSION: The interactive use of AutoCyte-Screen can effectively select those cases which are most likely to contain an epithelial abnormality and could therefore be used as a triage system to select cases for manual review. A case with an interactive result of unsatisfactory and abnormal should receive full manual review, while those classified as WNL may require a less extensive review for quality assurance purposes. This resultant decrease in the manual screening load could increase laboratory efficiency. PMID- 9987452 TI - Direct-to-vial use of the AutoCyte PREP liquid-based preparation for cervical vaginal specimens in three European laboratories. AB - OBJECTIVE: To compare the AutoCyte PREP direct-to-vial procedure to the conventional Pap smear in two large and similar patient groups compiled from the testing experience of three cytology laboratories in Switzerland and France. STUDY DESIGN: Randomly selected, large patient groups were evaluated using either the conventional Pap smear or the AutoCyte PREP direct-to-vial liquid-based preparation. Results were then compared statistically as to disease detection and sample adequacy. RESULTS: Specimen adequacy was greatly improved in the group tested with the AutoCyte PREP. PREP also demonstrated a significant reduction in ASCUS and ASCUS:LSIL+ ratios. The three laboratories participating in this review found significantly improved detection of both low and high grade SIL. Routine use of AutoCyte PREP for cervical cytology screening offers substantial improvements in adequacy and disease detection. PMID- 9987453 TI - Cell block preparation as a diagnostic technique complementary to fluid-based monolayer cervicovaginal specimens. AB - OBJECTIVE: To determine whether preparation of cell blocks from fluid-based cervicovaginal specimens can add to the diagnostic accuracy of monolayer preparations from the same specimens. STUDY DESIGN: Cell block preparations were made from 100 cervicovaginal, fluid-based ThinPrep Pap test specimens. These specimens were collected in a fluid-based solution with a Papette or cytology brush and a scraper. After a monolayer slide was made, a determination was made if a cell block preparation was needed based on the morphologic findings on the slide. RESULTS: Cell block results aided the ThinPrep Pap diagnosis in 20% of specimens and were critical to the diagnosis in 5%. The cell block preparation was most useful in lesions where architecture and morphology were important, such as immature squamous metaplasia versus high grade squamous intraepithelial lesion, repair versus squamous carcinoma and tubal metaplasia versus atypical glandular cells of undetermined significance. It was also found that the presence of tissue fragments rather than single cells on the slide was an indication of the possibility that a cell block was productive. CONCLUSION: Cell block preparation in selected cases can be a valuable adjunct to monolayer slide preparations in the diagnosis of cervicovaginal lesions. PMID- 9987454 TI - Comparison of ThinPrep and Pap smear in relation to prediction of adenocarcinoma in situ. AB - OBJECTIVE: To compare the accuracy of reporting split-sample ThinPrep (SSTP) and the Pap smear (PS) in cases of histologically confirmed adenocarcinoma in situ (AIS) and to ascertain the reasons for any discrepancies. STUDY DESIGN: Comparison of prospective PS and ThinPrep (TP) predictions with unblinded review of TP slides. RESULTS: In 30 paired cytologic samples, AIS was originally accurately predicted by PS in 20 (67%) and SSTP in 14 (47%). In the 16 cases in which SSTP failed to predict AIS, on review 4 were regarded as cytologic undercalls, and in the remaining 12 no diagnostic material was found on the first TP slide. In eight of these, further TP slides were made; in three, diagnostic material was present on subsequent TP slides, and in five it was not. Differences in cytologic appearances of AIS were noted between TP and PS. CONCLUSION: Even though in routine practice SSTP did not perform as well as PS in predicting AIS, it has the potential to do so. These results cannot anticipate the performance of direct-to-vial TP with respect to prediction of AIS. PMID- 9987455 TI - ThinPrep Pap Test. Accuracy for glandular disease. AB - OBJECTIVE: Although the ThinPrep Pap Test is replacing conventional Pap smears in many clinical practices, experience with the identification of glandular lesions is limited. In this study, ThinPrep cytology of glandular lesions was evaluated in a large, inner city teaching hospital with high rates of glandular abnormality. STUDY DESIGN: Six months of ThinPrep diagnoses in 1998, following nearly 100% conversion of the laboratory to the ThinPrep Pap Test, were compared to January-December 1997 conventional smear diagnoses for glandular disease. Biopsy confirmation was evaluated for these cases. Findings on all biopsy confirmed glandular cases were also compared to findings on cytology. RESULTS: Similar overall rates of glandular cytology were found. For conventional smears (12 months), 46 cases were diagnosed out of 43,289 smears (0.11%). For ThinPrep cytology (six months), 36 cases were diagnosed out of 25,783 slides (0.14%, P = NS). In the year 1997, 9 biopsy-confirmed conventional smear diagnoses of adenocarcinoma in situ (AIS) or adenocarcinoma were noted versus 10 for six months of 1998 for the ThinPrep method. A statistically significant reduction in the number of miscellaneous nonglandular (squamous) biopsy diagnoses were found with ThinPrep glandular cytology (14 vs. 4 cases, P < .05). For known biopsy confirmed glandular cases of AIS or adenocarcinoma, a statistically significant reduction in the cytology false negative rate was noted with the ThinPrep method (17 vs. 4 cases, P < .02). CONCLUSION: The ThinPrep method provides more accurate diagnoses of glandular disease, with an increase in both sensitivity and specificity for glandular lesions. PMID- 9987456 TI - 100% rapid (partial) rescreening for quality assurance. AB - OBJECTIVE: To compare the efficiency of two methods for routine quality assurance in gynecologic cytology: random rescreening of 10% of negative gynecologic smears and rapid rescreening of all negative gynecologic smears. STUDY DESIGN: All gynecologic smears considered to be negative or benign and diagnosed between November 1, 1996, and December 31, 1997, were rescreened using the rapid, partial rescreening technique. Results were compared to those of the 10% random rescreening method. RESULTS: Comparing the 10% review of negatives to the rapid rescreening in two comparable periods of three months, the former required review by the supervisor of 160 cases in order to find a true false negative. With rapid rescreening, the supervisor had to review fewer than eight cases to find a true false negative. Also, rapid rescreening found about four times more true false negatives than random 10% review. CONCLUSION: Rapid rescreening of all negative gynecologic smears proved more efficient than 10% random rescreening. PMID- 9987457 TI - Surveillance and prevention of hepatitis B virus transmission. PMID- 9987458 TI - Prevalence of hepatitis B virus infection in the United States: the National Health and Nutrition Examination Surveys, 1976 through 1994. AB - OBJECTIVE: Data from 2 National Health and Nutrition Examination Surveys (NHANES), NHANES II (1976-1980) and NHANES III (1988-1994), were analyzed to examine trends in the prevalence of hepatitis B infection in the United States. METHODS: Serum specimens were tested for markers of hepatitis B virus infection, and risk factors were determined from questionnaires. RESULTS: The overall age adjusted prevalence of hepatitis B virus infection was 5.5% (95% confidence interval [CI] = 4.8, 6.2) in NHANES II, as compared with 4.9% (95% CI = 4.3, 5.6) in NHANES III. In both surveys, Black participants had the highest prevalence of infection (NHANES II, 15.8%; NHANES III, 11.9%). No differences in infection were found in the major racial groups between surveys, except for a decrease among those older than 50 years. Black race, increasing number of lifetime sexual partners, and foreign birth had the strongest independent associations with hepatitis B virus infection. CONCLUSIONS: Testing of participants in 2 national surveys demonstrates no significant decrease in hepatitis B virus infection, despite the availability of hepatitis B vaccine. PMID- 9987459 TI - Assessing prenatal hepatitis B screening in Illinois with an inexpensive study design adaptable to other jurisdictions. AB - OBJECTIVES: This study estimated, using an economical survey design adaptable to other jurisdictions, the proportion of birth admissions in Illinois hospitals in which mothers were not screened for hepatitis B surface antigen prior to delivery. It also identified factors associated with lack of screening. METHODS: Based on a cluster sampling design, 1372 birth records were sampled, and data were abstracted by local personnel at 56 hospitals. Selected data elements were reabstracted on a subsample to evaluate recording errors. RESULTS: Reabstracted data demonstrated 95% agreement among reviewers. Hepatitis B surface antigen screening was documented for 90.7% of mothers; 11% of responding hospitals accounted for 45% of nonscreened mothers. Risk factors for not being screened included no prenatal care, Medicaid or no insurance, and delivery at a hospital lacking a written hepatitis B surface antigen policy. CONCLUSIONS: In Illinois, prenatal hepatitis B surface antigen screening rates were high and similar to those in other states. Births without screening or transferred information clustered in a few hospitals. The methods used here can economically identify underscreened populations by sampling a large number of hospitals within designated areas. PMID- 9987460 TI - Breast-feeding and infant illness: a dose-response relationship? AB - OBJECTIVES: The purpose of this study was to determine whether breast-feeding has a dose-related protective effect against illness and whether it confers special health benefits to poor infants. METHODS: The association between breast-feeding dose and illnesses in the first 6 months of life was analyzed with generalized estimating equations regression for 7092 infants from the National Maternal and Infant Health Survey. Breast-feeding dose (ratio of breast-feedings to other feedings) was categorized as full, most, equal, less, or no breast-feeding. RESULTS: Compared with no breast-feeding, full breast-feeding infants had lower odds ratios of diarrhea, cough or wheeze, and vomiting and lower mean ratios of illness months and sick baby medical visits. Most breast-feeding infants had lower odds ratios of diarrhea and cough or wheeze, and equal breast-feeding infants had lower odds ratios of cough or wheeze. Full, most, and equal breast feeding infants without siblings had lower odds ratios of ear infections and certain other illnesses, but those with siblings did not. Less breast-feeding infants had no reduced odds ratios of illness. Findings did not vary by income. CONCLUSIONS: Full breast-feeding was associated with the lowest illness rates. Minimal (less) breast-feeding was not protective. Breast-feeding conferred similar health benefits in all economic groups. PMID- 9987461 TI - Consequences in Georgia of a nationwide outbreak of Salmonella infections: what you don't know might hurt you. AB - OBJECTIVES: This study assessed the impact in Georgia of a nationwide salmonellosis outbreak caused by ice cream products and the effectiveness of the subsequent warning against eating the implicated products. METHODS: A telephone survey of 250 randomly selected Georgia customers of the ice cream producer was conducted 13 to 17 days after the warning. RESULTS: Respondents from 179 households representing 628 persons were interviewed. The median date of first hearing the warning was 5 days after it was issued, and 16 respondents (9%) had not heard it. Among those who had heard the warning, 42 (26%) did not initially believe the products were unsafe. In 22 (31%) of the 72 households that had the implicated ice cream when the respondent heard the warning, someone subsequently ate the ice cream. Diarrhea was reported in 26% (121/463) of persons who had eaten the products but in only 5% (8/152) who had not (odds ratio [controlling for household clustering] = 3.8; 95% confidence interval = 2.0, 7.5). We estimate this outbreak caused 11,000 cases of diarrhea in Georgia, 1760 (16%) with exposure after the warning. CONCLUSIONS: A large outbreak occurred in Georgia, much of which might have been prevented by a more timely and convincing warning. PMID- 9987462 TI - Going bare: trends in health insurance coverage, 1989 through 1996. AB - OBJECTIVES: This study analyzed trends in health insurance coverage in the United States from 1989 through 1996. METHODS: Data from annual cross-sectional surveys by the US Census Bureau were analyzed. RESULTS: Between 1989 and 1996, the number of uninsured persons increased by 8.3 million (90% confidence interval [CI] = 7.7, 8.9 million). In 1996, 41.7 million (90% CI = 40.9, 42.5 million) lacked insurance. From 1989 to 1993, the proportion with Medicaid increased by 3.6 percentage points (90% CI = 3.1, 4.0), while the proportion with private insurance declined by 4.2 percentage points (90% CI = 3.7, 4.7). From 1993 to 1996 private coverage rates stabilized but did not reverse earlier declines. Consequently, the number uninsured continued to increase. The greatest increase in the population of uninsured [corrected] was among young adults aged 18 to 39 years; rates among children also rose steeply after 1992. While Blacks had the largest percentage increase, Hispanics accounted for 36.4% (90% CI = 32.3%, 40.5%) of the increase in the number uninsured. From 1989 to 1993, the majority of the increase was among poor families. Since then, middle-income families have incurred the largest increase. Northcentral and northeastern states had the largest increases in percent uninsured. CONCLUSIONS: Despite economic prosperity, the numbers and rates of the uninsured continued to rise. Principally affected were children and young adults, poor and middle income families, blacks, and Hispanics. PMID- 9987463 TI - Syringe exchange in the United States, 1996: a national profile. AB - OBJECTIVES: This paper provides 1996 information on the status of US syringe exchange programs and compares these findings with data from our 1994 survey. METHODS: In November 1996, questionnaires were mailed to 101 syringe exchange programs. Program directors were contacted to conduct telephone interviews based on the mailed questionnaires. Data collected included number of syringes exchanged, syringe exchange program operations, legal status, and services offered. RESULTS: Eighty-seven programs participated in the survey. A total of 46 (53%) were legal, 20 (23%) were illegal but tolerated, and 21 (24%) were illegal underground. Since 1994, there has been a 54% increase in the number of cities and a 38% increase in the number of states with syringe exchange programs. Eighty four programs reported exchanging approximately 14 million syringes, a 75% increase from 1994. Syringe exchange programs also provided a variety of other services and supplies, and legal programs were more likely than illegal ones to provide these services. CONCLUSION: Despite continued lack of federal funding, syringe exchange programs expanded in terms of the number of syringes exchanged, the geographic distribution of programs, and the range of services offered. PMID- 9987464 TI - Occupational class and ischemic heart disease mortality in the United States and 11 European countries. AB - OBJECTIVES: Twelve countries were compared with respect to occupational class differences in ischemic heart disease mortality in order to identify factors that are associated with smaller or larger mortality differences. METHODS: Data on mortality by occupational class among men aged 30 to 64 years were obtained from national longitudinal or cross-sectional studies for the 1980s. A common occupational class scheme was applied to most countries. Potential effects of the main data problems were evaluated quantitatively. RESULTS: A north-south contrast existed within Europe. In England and Wales, Ireland, and Nordic countries, manual classes had higher mortality rates than nonmanual classes. In France, Switzerland, and Mediterranean countries, manual classes had mortality rates as low as, or lower than, those among nonmanual classes. Compared with Northern Europe, mortality differences in the United States were smaller (among men aged 30-44 years) or about as large (among men aged 45-64 years). CONCLUSIONS: The results underline the highly variable nature of socioeconomic inequalities in ischemic heart disease mortality. These inequalities appear to be highly sensitive to social gradients in behavioral risk factors. These risk factor gradients are determined by cultural as well as socioeconomic developments. PMID- 9987465 TI - Increasing fruit and vegetable consumption through worksites and families in the treatwell 5-a-day study. AB - OBJECTIVES: We report on the results of the Treatwell 5-a-Day study, a worksite intervention aimed at increasing consumption of fruits and vegetables. METHODS: Twenty-two worksites were randomly assigned to 3 groups: (1) a minimal intervention control group, (2) a worksite intervention, and (3) a worksite-plus family intervention. The interventions used community-organizing strategies and were structured to target multiple levels of influence, following a socioecological model. Data were collected by self-administered employee surveys before and after the intervention; the response rate was 87% (n = 1359) at baseline and 76% (n = 1306) at follow-up. A process tracking system was used to document intervention delivery. RESULTS: After control for worksite, gender, education, occupation, race/ethnicity, and living situation, total fruit and vegetable intake increased by 19% in the worksite-plus-family group, 7% in the worksite intervention group and 0% in the control group (P = .05). These changes reflect a one half serving increase among workers in the worksite-plus-family group compared with the control group (P = .018). CONCLUSIONS: The worksite-plus family intervention was more successful in increasing fruit and vegetable consumption than was the worksite intervention. Worksite interventions involving family members appear to be a promising strategy for influencing workers' dietary habits. PMID- 9987468 TI - Universal HIV screening at a major metropolitan TB clinic: HIV prevalence and high-risk behaviors among TB patients. AB - OBJECTIVES: This study assessed the outcome of implementing a policy of universal screening of patients with tuberculosis (TB) for HIV infection at a major metropolitan public health TB clinic. METHODS: HIV serologic testing was completed on 768 (93%) of 825 eligible patients. Ninety-eight HIV-positive cases (13%) were compared with 670 HIV-negative cases. The presence of adult HIV risk factors was determined by structured interview and review of medical records. RESULTS: One or more HIV risk factors were present in 93% of HIV-positive cases and 42% of HIV-negative cases. CONCLUSIONS: The metropolitan TB clinic is well suited for HIV screening, and HIV-antibody testing and counseling should be provided to all TB patients. PMID- 9987466 TI - Can data-driven benchmarks be used to set the goals of healthy people 2010? AB - OBJECTIVES: Expert panels determined the public health goals of Healthy People 2000 subjectively. The present study examined whether data-driven benchmarks provide a better alternative. METHODS: We developed the "pared-mean" method to define from data the best achievable health care practices. We calculated the pared-mean benchmark for screening mammography from the 1994 National Health Interview Survey, using the metropolitan statistical area as the "provider" unit. Beginning with the best-performing provider and adding providers in descending sequence, we established the minimum provider subset that included at least 10% of all women surveyed on this question. The pared-mean benchmark is then the proportion of women in this subset who received mammography. RESULTS: The pared mean benchmark for screening mammography was 71%, compared with the Healthy People 2000 goal of 60%. CONCLUSIONS: For Healthy People 2010, benchmarks derived from data reflecting the best available care provide viable alternatives to consensus-derived targets. We are currently pursuing additional refinements to the data-driven pared-mean benchmark approach. PMID- 9987467 TI - Exercise--it's never too late: the strong-for-life program. AB - OBJECTIVES: This investigation determined whether an in-home resistance training program achieved health benefits in older adults with disabilities. METHODS: A randomized controlled trial compared the effects of assigning 215 older persons to either a home-based resistance exercise training group or a waiting list control group. Assessments were conducted at baseline and at 3 and 6 months following randomization. The program consisted of videotaped exercise routines performed with elastic bands of varying thickness. RESULTS: High rates of exercise adherence were achieved, with 89% of the recommended exercise sessions performed over 6 months. Relative to controls, subjects who participated in the program achieved statistically significant lower extremity strength improvements of 6% to 12%, a 20% improvement in tandem gait, and a 15% to 18% reduction in physical and overall disability at the 6-month follow-up. No adverse health effects were encountered. CONCLUSIONS: These findings provide important evidence that home-based resistance exercise programs designed for older persons with disabilities hold promise as an effective public health strategy. PMID- 9987469 TI - Reducing AIDS risk among port workers in Santos, Brazil. AB - OBJECTIVES: This study examined the impact of worksite-based AIDS prevention program among port workers in Santos, Brazil, on sexual risk behavior for HIV infection. METHODS: Male port workers (n = 226) were followed in a 3-wave prospective cohort study. A multifaceted intervention costing US $90,000 for 20,000 workers was conducted between waves 2 and 3. RESULTS: Heterosexual risk behavior showed no decline between waves 1 and 2 (before the intervention) but decreased substantially between waves 2 and 3 (after the intervention). This decrease resulted from both a decrease in nonprimary partners and an increase in condom use. CONCLUSIONS: This worksite-based AIDS program produced marked behavior change at modest cost. PMID- 9987470 TI - Persistence of susceptibility to measles in France despite routine immunization: a cohort analysis. AB - OBJECTIVES: This study examined the impact of French routine programs urging the combined measles-mumps-rubella immunization of 15-month-old children. METHODS: We applied a cohort analysis to surveillance data collected by general practitioners to estimate the cumulative incidence rate per 1000 unvaccinated children and the proportion of susceptible children, by age and for each birth cohort between 1985 and 1995. RESULTS: More than 70% of unvaccinated children born in 1985 and 1986 had measles by the age of 10. This incidence rate dramatically decreased after implementation of the routine measles-mumps-rubella immunization program in 1989, but the proportion of 5-year-olds susceptible to measles has not decreased appreciably. In 1996, more than 15% of the children born between 1990 and 1995 were susceptible. CONCLUSIONS: The measles vaccine coverage achieved by the French routine immunization program remains insufficient as regards reducing the number of susceptible children. PMID- 9987471 TI - Peptic ulcer disease and exposure to domestic pets. AB - OBJECTIVES: This study assessed whether an association exists between household pets and peptic ulcer disease. METHODS: Canadian adults (n = 15,779) were asked about cats or dogs in their household and about history of peptic ulcer disease. Logistic regression was used to assess the association between pet ownership and a history of peptic ulcer disease, after adjustment for sociodemographic differences. RESULTS: No relationship was observed between report of household pets and a history of peptic ulcer disease (adjusted odds ratio = 1.14, 95% confidence interval = 0.95, 1.36). CONCLUSIONS: In a large sample of Canadian adults, no association was observed between pet ownership and a history of peptic ulcer disease. PMID- 9987472 TI - Sensory impairment and driving: the Blue Mountains Eye Study. AB - OBJECTIVES: This study examined the associations between vision, hearing, loss, and car accidents. METHODS: A cross-sectional survey of 3654 people aged 49 years and older in the Blue Mountains, Australia, was used. Each subject had a detailed eye examination and interview. RESULTS: Self-reported car accident rates in the past year among 2379 current drivers were 5.6% for those aged 49 to 79 years and 9.1% for those 80 years and older. A 2-line difference in visual acuity was associated with increased risk of accidents (adjusted prevalence ratio [PR] = 1.6), as was visual acuity worse than 6/18 in the right eye (PR = 2.0), overall moderate hearing loss (PR = 1.9), and hearing loss in the right ear (PR = 1.8). CONCLUSIONS: Sensory loss in drivers may be an important risk factor for car accidents. PMID- 9987473 TI - Effectiveness of denial of handgun purchase to persons believed to be at high risk for firearm violence. AB - OBJECTIVES: The purpose of this study was to determine whether denial of handgun purchase is an effective violence prevention strategy. METHODS: Individuals denied handgun purchase because of a prior felony conviction and handgun purchasers with a felony arrest at time of purchase were examined. RESULTS: Relative to those denied purchase, handgun purchasers were found to be at greater risk for subsequent offenses involving a gun (relative risk [RR] = 1.21, 95% confidence interval [CI] = 1.08, 1.36) or violence (RR = 1.24, 95% CI = 1.11, 1.39), after adjustment for number of prepurchase weapon/violence charges. CONCLUSIONS: Denial of handgun purchase to persons with a prior felony conviction may lower their rate of subsequent criminal activity. PMID- 9987474 TI - Deaths attributable to Alzheimer's disease in the United States. AB - OBJECTIVES: This study provided 2 estimates of the number of deaths attributable to Alzheimer's disease in the United States. METHODS: One estimate was based on data from the East Boston, Mass, study. The second was based on a simulation using population-based estimates of prevalence and separate estimates of excess death by duration of disease. RESULTS: Despite different methods and very different estimates of prevalence, these 2 methods led to very similar estimates of 173,000 and 163,000 excess deaths. CONCLUSIONS: These estimates suggest that 7.1% of all deaths in the United States in 1995 are attributable to Alzheimer's disease, placing it on a par with cerebrovascular diseases as the third leading cause of death. PMID- 9987475 TI - Vasectomy in the United States, 1991 and 1995. AB - OBJECTIVES: This study sought to assess whether the controversy surrounding publications linking vasectomy and prostate cancer has had an effect on vasectomy acceptance and practice in the United States. METHODS: National probability surveys of urology, general surgery, and family practices were undertaken in 1992 and 1996. RESULTS: Estimates of the total number of vasectomies performed, population rate, and proportion of practices performing vasectomy were not significantly different in 1991 and 1995. CONCLUSIONS: This study provides no solid evidence that the recent controversy over prostate cancer has influenced vasectomy acceptance or practice in the United States. However, the use of vasectomy appears to have leveled off in the 1990s. PMID- 9987476 TI - Reading ability, education, and cognitive status assessment among older adults in Harlem, New York City. AB - OBJECTIVES: This study examined reported level of education and current reading ability as predictors of cognitive status among older African Americans in central Harlem, New York City. METHODS: A probability sample of 164 noninstitutionalized older African Americans was assessed. Mini-Mental State Examination (MMSE) scores were regressed on education and reading ability measures. RESULTS: Reading ability and educational attainment were significant, independent predictors of MMSE performance. Within any level of education, subjects whose grade-equivalent reading ability exceeded reported level of education scored significantly higher on the MMSE. CONCLUSIONS: Reading ability may be useful in interpreting the results of cognitive screening among low educated and minority groups. PMID- 9987477 TI - Thalidomide and the Titanic: reconstructing the technology tragedies of the twentieth century. AB - The Titanic has become a metaphor for the disastrous consequences of an unqualified belief in the safety and invincibility of new technology. Similarly, the thalidomide tragedy stands for all of the "monsters" that can be inadvertently or negligently created by modern medicine. Thalidomide, once banned, has returned to the center of controversy with the Food and Drug Administration's (FDA's) announcement that thalidomide will be placed on the market for the treatment of erythema nodosum leprosum, a severe dermatological complication of Hansen's disease. Although this indication is very restricted, thalidomide will be available for off-label uses once it is on the market. New laws regarding abortion and a new technology, ultrasound, make reasonable the approval of thalidomide for patients who suffer from serious conditions it can alleviate. In addition, the FDA and the manufacturer have proposed the most stringent postmarketing monitoring ever used for a prescription drug, including counseling, contraception, and ultrasonography in the event of pregnancy. The Titanic/thalidomide lesson for the FDA and public health is that rules and guidelines alone are not sufficient to guarantee safety. Continuous vigilance will be required to ensure that all reasonable postmarketing monitoring steps are actually taken to avoid predictable and preventable teratogenic disasters. PMID- 9987478 TI - Public health developments in colonial Malaya: colonialism and the politics of prevention. AB - In both African and Asian colonies until the late 19th century, colonial medicine operated pragmatically to meet the medical needs first of colonial officers and troops, immigrant settlers, and laborers responsible for economic development, then of indigenous populations when their ill health threatened the well-being of the expatriate population. Since the turn of the century, however, the consequences of colonial expansion and development for indigenous people's health had become increasingly apparent, and disease control and public health programs were expanded in this light. These programs increased government surveillance of populations at both community and household levels. As a consequence, colonial states extended institutional oversight and induced dependency through public health measures. Drawing on my own work on colonial Malaya, I illustrate developments in public health and their links to the moral logic of colonialism and its complementarity to the political economy. PMID- 9987479 TI - Condom use in female sex workers in Italy. PMID- 9987480 TI - The protective effect of condoms and nonoxynol-9 against HIV infection: a response to Wittkowski and colleagues. PMID- 9987481 TI - Cost-effectiveness and Down syndrome. PMID- 9987482 TI - Carbon monoxide poisoning in the aftermath of hurricane Fran. PMID- 9987483 TI - [Diagnosis and surgical treatment of atrial septal defects in adults]. AB - BACKGROUND AND OBJECTIVE: The value of surgical closure of an atrial septal defect (ASD) in adults is currently under discussion, because the operative risk is thought to be high and there are no reliable data about postoperative change in quality of life. PATIENTS AND METHODS: The case notes of 205 patients (149 women, 56 men, mean age 41.4 years) in whom an ASD had been surgically closed were analysed retrospectively. Preoperative symptoms, complications, arrhythmias, pulmonary artery pressure and the influence of the operative closure on quality of life (criteria of the New York Heart Association [NYHA]) were noted. RESULTS: At the time of diagnosis 138 (66%) of patients had complained of dyspnoea or palpitations, four had sustained a stroke and two had had endocarditis. Atrial fibrillation or flutter was present in 55 (27%). 47 (23%) were in class III or IV (NYHA). Mean age at operation was 42.2 (18-74.9) years. One patient, a woman with pulmonary hypertension, died and one patient suffered a stroke. The number of patients with atrial fibrillation or flutter fell to 31 (15%) postoperatively and 176 patients (86%) moved to a better NYHA class, especially those who had been in class IV. CONCLUSIONS: These data show that surgical closure of ASD in adults is reasonable, because the operative mortality is low, the quality of life is improved postoperatively and there is a reduced incidence of arrhythmias. PMID- 9987484 TI - [Unusual case of disseminated sarcoidosis with prominent gastrointestinal symptoms]. AB - HISTORY AND ADMISSION FINDINGS: A 63-year-old man had for 10 months suffered from marked weight loss, night sweats, diffuse abdominal pain and increased stool frequency. He was admitted to evaluate an ultrasonically abnormal focus in the liver parenchyma and elevated liver function parameters. His sclerae were obviously icteric and he looked under-weight. INVESTIGATIONS: He had a hypochromic microcytic anemia and abnormal liver and pancreatic function tests: total bilirubin 3.11 mg/dl, direct bilirubin 2.21 mg/dl, GOT21U/l, gamma-GT 422 U/l, alkaline phosphatase 1449 U/l, alpha-amylase 481 U/l, lipase 2827 U/l. The serum creatinine level was elevated to 1.47 mg/dl. Computed tomography revealed enlarged liver and spleen as well as an enlargement of intraabdominal lymph nodes, chest radiogram and endoscopic cholangio-pancreatography were unremarkable. Biopsies from the lower duodenum, large intestine, bone marrow and liver showed inflammatory changes with Langhans-type mononuclear granulomas. Together with these findings an increased activity of the angiotensin-converting enzyme (ACE) indicated sarcoidosis, other causes having been excluded. TREATMENT AND COURSE: All signs and symptoms rapidly improved under prednisolone, and 4 weeks after begin of treatment the biochemical abnormalities had clearly regressed. The raised serum levels of soluble IL-2 receptors and of neopterin, measures of sarcoidosis activity, had decreased. Activity of ACE had fallen. CONCLUSION: Sarcoidosis can present with diverse clinical signs and symptoms. In a case of multi-system disease that cannot be readily classified, sarcoidosis should be included in the differential diagnosis. PMID- 9987485 TI - [Focal mycobacterial lymphadenitis after starting highly active antiretroviral therapy]. AB - HISTORY AND FINDINGS: A 30-year-old man with a known HIV infection for 7 years presented for treatment with antiretroviral drugs. He was known to have had herpes zoster, oral hairy leukoplakia and recurrent Candida stomatitis, but was otherwise without symptoms. INVESTIGATIONS: The CD4 lymphocyte count was 19 cells/mm3 and there were 41,000 HIV-RNA copies/ml. DIAGNOSIS, TREATMENT AND COURSE: The HIV infection was in CDC stage B3, indicating the need for combined antiretroviral treatment. A week after starting stavudine, saquinavir and ritonavir he had to be admitted because of nausea and vomiting, colicky abdominal pain, diarrhea, fever up to 39 degrees C and a rise of C-reactive protein to 207 mg/dl. Bacteriological examination of feces and biopsy of an enlarged retroperitoneal lymph node revealed atypical mycobacteria. Antituberculosis treatment was started. The CD4 cell count rose to 56/mm3 and the viral count fell to 11,000/ml. Each time after initiating a different antiviral regimen the symptoms recurred. CONCLUSIONS: This case illustrates an atypical manifestation of on opportunistic infection: during combined antiviral treatment the CD4 cell count rose and thus precipitated an heretofore subclinical mycobacterial infection with focal lymphadenitis. If, on starting antiretroviral treatment at a late HIV stage, new symptoms develop within 1-3 weeks, one should consider drug induced side effects or the onset of an opportunistic infection that has become manifest as the result of an improved immunological state. PMID- 9987487 TI - [Gastroesophageal reflux disease]. PMID- 9987486 TI - [11 beta-hydroxysteroid dehydrogenases: key enzymes in the action of mineralocorticoids and glucocorticoids]. PMID- 9987488 TI - [Social jurisdiction]. PMID- 9987489 TI - [Air embolism]. PMID- 9987490 TI - [Esophageal motility disorders in diabetics]. PMID- 9987491 TI - [Inadvertent intravenous injection of adrenaline]. PMID- 9987492 TI - [Heparin-induced thrombocytopenia type II]. PMID- 9987493 TI - Advances in the diagnosis and management of impotence. PMID- 9987494 TI - [Gene therapy using anticancer drug-resistance genes]. AB - Myelosuppression is a major dose-limiting factor in cancer chemotherapy. Introduction of drug-resistance genes into bone marrow cells of cancer patients has been proposed to overcome this limitation. In theory, any gene whose expression protects cells against the toxic effects of chemotherapy should be useful in vivo for this purpose. Among such genes, human multidrug-resistance gene (MDR1) and O6-methylguanine DNA methyltransferase gene (MGMT) have been studied most extensively for this purpose, and clinical trials of drug-resistance gene therapy have been started in the US for cancer patients who undergo high dose chemotherapy with autologous hematopoietic stem cell transplantation. In Japan, our clinical protocol of MDR1 gene therapy, "A clinical study of drug resistance gene therapy to improve the efficacy and safety of chemotherapy against breast cancer", has been approved by our IRB and submitted to the government. To improve the efficacy and safety of this drug-resistance gene therapy, we have constructed a series of MDR1-bicistronic retrovirus vectors using a retrovirus backbone of Harvey murine sarcoma virus and internal ribosome entry site (IRES) from picornavirus to coexpress a second gene with the MDR1 gene. MDR1-MGMT bicistronic vectors can be used to protect bone marrow cells of cancer patients from combination chemotherapy with MDR1-related anticancer agents and nitrosoureas. In addition, MDR1-bicistronic retrovirus vectors can be designed to use the MDR1 gene as an in vivo selectable marker to enrich the transduced cells which express therapeutic genes, if disease is curable by the expression of a single-peptide gene in bone marrow cells or any types of peripheral blood cells. PMID- 9987495 TI - Surgery and multimodal treatments in pancreatic cancer--a review on the basis of future multimodal treatment concepts. AB - BACKGROUND: To improve the surgical outcome after resection of pancreatic adenocarcinomas, multimodal treatment concepts need to be applied and improved. In spite of several positive studies, and the fact that multimodality treatment is the standard concept in major centers for pancreatic cancer surgery, a recent trial shed some doubt on the positive effect of adjuvant radiochemotherapy, so that the majority with reservations about multimodal treatment feel confirmed in their opinion that surgical treatment alone is sufficient therapy for resectable pancreatic cancer. The controversy among those for and against adjuvant treatment need an up-to-date review of the indications and results achievable with various treatment modalities. PATIENTS/METHODS: The literature on the indications and results of adjuvant/neoadjuvant therapies in pancreatic cancer was reviewed to provide a solid base for current recommendations and future developments. A special view was concentrated on the biology of the disease in the spontaneous course, after surgery and during/after various palliative and adjuvant/neoadjuvant treatment modalities, to characterize the disease for an optimally targeted treatment in conjunction with surgical removal of the tumor. The results of systemic and regional chemotherapy and radiotherapy either alone or in combination, before, during, and after surgery, were critically analyzed with respect to the oncological possibilities and pitfalls of each treatment method. RESULTS: In two randomized trials, one testing postoperative radiochemotherapy (GITSG), and one postoperative chemotherapy (Bakkevold), the adjuvant treatment achieved a significant prolongation of the median survival time. The 5- and 10-year survival rates were improved in the GITSG study. The EORTC-GITCCG trial could not confirm the benefit of adjuvant radiochemotherapy. This study had a different design than the GITSG trial. Several historical control studies supported the beneficial effect of postoperative radiochemotherapy. In three historical control trials using regional chemotherapy, one with intraoperative radiotherapy, the survival times were improved vs. surgery alone. Intraoperative or postoperative radiotherapy as single modalities might reduce local relapses, but a survival advantage is still debated. Preoperative neoadjuvant radiochemotherapy has several advantages (downstaging, devitalizing margins and lymph node metastases, compatibility of treatment vs. postoperative radiochemotherapy), and does not seem to increase the postoperative morbidity. Several trials have confirmed the feasibility of this concept, but no survival advantage has yet been proven. Systemic and regional chemotherapy is able to downstage primarily nonresectable pancreatic cancers. CONCLUSIONS: Postoperative adjuvant radiochemotherapy with up-to-date protocols can be recommended for routine treatment, if the surgeon or the patient desires to improve the usually remote prognosis after surgery alone. For those being undecisive or against adjuvant therapy, the participation in trials, e.g., ESPAC 1 and 2 studies, is strongly recommended. Regarding our own positive experience with adjuvant regional chemotherapy and in view of the postresectional progression pattern, we currently favour adjuvant radiochemotherapy, with the chemotherapy delivered regionally via the celiac axis. This concept will be tested vs. surgery alone in the ESPAC 2 trial. Neoadjuvant therapies have a great potential, but should be conducted within studies, such as pre-, intra-, or postoperative radiotherapy. PMID- 9987496 TI - [Differences in therapeutic strategies for adult leukemia and lymphoma between Japan and western countries]. AB - The purpose of this paper is to clarify the differences in therapeutic strategies for adult leukemia and lymphoma between Japan and western countries. Since in Japan, high-dose cytarabine for acute leukemia is not covered by health insurance, post-remission therapy might be less intense compared to western countries and it takes a long time to complete the therapy. The results of chemotherapy for adult acute lymphocytic leukemia (ALL) in Japan have been inferior to those in foreign reports. Accordingly, many Japanese hematologists believe that adult ALL has a worse prognosis than acute myeloid leukemia (AML), and almost all young adult patients with ALL should receive allogeneic bone marrow transplantation (BMT) from related or unrelated donors. Japanese hematologists also consider that Interferon as the first-line chemotherapy for chronic myelogenous leukemia (CML), and that BMT from a HLA matched sibling donor should be done as soon as possible. Recently, some foreign reports of BMT from unrelated donors for CML revealed results comparable to BMT from related donors showing that even transplants from unrelated donors should be done as soon as possible. Since chronic lymphocytic leukemia and Hodgkin's disease are so rare in Japan, the available drugs for these diseases are limited. The quality and quantity of Japanese clinical studies in this field are inferior to studies in western countries. This, in fact, is a more serious problem than the differences in therapeutic strategies. PMID- 9987497 TI - [Lung cancer]. AB - The five year survival rate of lung cancer patients is only 10% in Japan. The staging system of c-TNM is more important than p-TNM when deciding treatment modality for lung cancer. Compared to other solid cancers, neoadjuvant therapy in lung cancer treatment has a more important position. A clinical protocol study should be carried out with the idea of "intent to treat" and medical oncology will play a more important role in the treatment of lung cancer. PMID- 9987498 TI - [Comparison in strategies for advanced head and neck squamous cell carcinomas between Japan and western countries]. AB - The recent strategies for advanced head and neck squamous cell carcinoma (HNSCC) were reviewed and compared between Japan and western countries. The curative treatments for advanced HNSCC are radiotherapy and/or surgical resection. These standard treatment modalities are the same in both areas. However, combined treatment, especially including impact chemotherapy, was developed in western countries earlier than in Japan. The organ preservation modality to preserve the organ and physiological function has been under investigation in controlled randomized trials in western countries. Patients with advanced HNSCC, for example, achieving a complete response at the primary lesion after neo-adjuvant chemotherapy followed by curative radiotherapy or concomitant chemoradiotherapy including impact chemotherapy, receive organ-sparing treatment. This strategy for advanced HNSCC in Japan promises to be widespread in future. PMID- 9987499 TI - [Difference in strategy for breast cancer between western countries and Japan]. AB - The history of breast cancer treatment has been largely that of western countries. Although Japan has had its own technological development, it does not have its own strategy for cancer treatment, especially for breast cancer. Thus the difference between western countries and Japan is obvious: USA and European countries are superior because of their scientific way of clinical research, such as "prospective randomized study", which has never been performed in Japan. We need to review our medical system in order to develop our own more effective types of therapy. PMID- 9987500 TI - [Gynecologic oncologists and their practice in the U.S.A]. AB - The development of gynecologic oncology in the U.S.A. was briefly reviewed and the differences in treatment approaches to gynecologic cancers between Japan and U.S.A. were described. In 1969, the Society of Gynecologic Oncologists was organized and the subspecialty of gynecologic oncology was created as a subsidiary division of the American Board of Obstetrics and Gynecology in 1970. In the same year the Gynecologic Oncology Group, which is a national collaborative research group, was established. It was decided that a gynecologic oncologist should have training and skills in all effective forms of treatment of gynecologic cancers: radical pelvic surgery, radiation therapy and chemotherapy. This subspecialty was a real success and became the model for such systems throughout the world. The role of the gynecologic oncologist is being recognized by the public in the U.S.A. Treatment approaches to cervical cancer, endometrial cancer and ovarian cancer in the U.S.A., which are different from ours, are also briefly described. PMID- 9987501 TI - [Prostate cancer]. AB - Although the incidence of latent or incidental cancer of the prostate is quite similar among Japanese and Americans, the incidence of clinically manifest prostate cancer and the mortality rates of prostate cancer are significantly higher in the latter. But, recently, the incidence of clinical cancer in Japan has been increasing exponentially, and the change in dietary habits is considered to be a major cause of this increase. Comparing the histological differences of prostate cancer between the Japanese and the Americans, the cribriform pattern is predominant in Japanese clinically significant cancer. On the other hand, a simple glandular pattern is predominant in American clinically significant cancer. These differences between Japanese and American prostate cancer suggest that each prostate cancer arises from different sources. For the organ-confined prostate cancer (stage A2 and B); radical prostatectomy has been considered the definitive treatment. But radiotherapy is now considered another radical treatment for localized prostate cancer which results in reduced morbidity. A heavy particle beam and brachytherapy are an even more radical modality that can deliver a greater dose of radiation to a localized lesion without affecting the surrounding normal tissue. For locally advanced prostate cancer (stage C); For the purpose of downstaging and radical treatment of locally advanced prostate cancer, combination of neoadjuvant hormonal therapy and radical prostatectomy has been expected. This regimen resulted in a significant decrease of positive surgical margins, but did not result in decrease of PSA failure. The impact on patient survival will be determined by the long-term follow-up. For advanced prostate cancer (stage D); In the study of the comparison of bilateral orchiectomy with or without flutamide in stage D2 prostate cancer, neither significant improvement of combination group on progression-free survival nor overall survival has been shown. From this result, the true efficacy of MAB is not certain. PMID- 9987502 TI - [CBDCA, etoposide and epirubicin high-dose combination chemotherapy supported by peripheral blood stem cell transplantation (PBSCT) in metastatic breast cancer]. AB - Six metastatic breast cancer patients, including one brain metastasis, one lung metastasis, three local recurrences and one bone metastasis, underwent multidrug chemotherapy with CBDCA, Etoposide (ETP) and Epirubicin (EPI). Each patient received two courses of PBSC mobilization chemotherapies and subsequently received high-dose chemotherapies for at least two courses. CBDCA AUC 4, ETP 300 mg/m2 and EPI 40 mg/m2 were administered intravenously as a PBSC mobilization chemotherapy, and high-dose chemotherapies were performed under the regimen of CBDCA AUC 8, ETP 900 mg/m2 and EPI 60 mg/m2. Severe bone marrow suppression due to high-dose chemotherapies was off sct by autologous peripheral blood stem cell transplantation (PBSCT). The PBSC mobilization chemotherapies resulted in one CR, three PR, one NC and one PD in the six patients. The PD patient died before high dose chemotherapy. Consequently, the remaining five patients received the high dose chemotherapies, which achieved three CR, one PR and one PD in the five patients. The response rate of high-dose chemotherapy was 80% (4/5 cases). In overall outcome, three patients have continued 16, 12 and 10 months tumor-free survival, and three patients died of cancer progression. High-dose chemotherapy with CBDCA, ETP and EPI has led to increased CR rates in metastatic breast cancer, and such therapy has desirable effect on the patient's prognosis. PMID- 9987503 TI - [Neoadjuvant chemotherapy for advanced cervical cancer]. AB - Twenty-five patients with advanced cervical cancer (IIb-IVa) were treated with neoadjuvant chemotherapy followed by radical hysterectomy or radiotherapy. According to the evaluation by MRI, complete response was achieved in 2 cases and partial response in 17 cases. Eventually the response rate was 76%. The response rate was higher in squamous cell carcinomas (85%) than adenocarcinomas or adenosquamous carcinomas (67%). The histological effect is superior in squamous cell carcinomas than adenocarcinomas or adenosquamous carcinomas. Radical hysterectomy was performed in 5 cases of 11 (45%) stage III-IVa cervical cancers. There was no correlation between tumor size and response to NAC. NAC therapy may be useful therapy in advanced cervical cancers, especially squamous cell carcinomas. PMID- 9987504 TI - [Pilot late phase II study of KRN8602 (MX2), a novel anthracycline derivative, for acute leukemia--a dose finding study in combination]. AB - In order to determine the clinically optimal dose of KRN8602, a new anthracycline derivative, in combination therapy for acute leukemia, we performed a pilot late phase II study in combination with cytarabine (Ara-C) for acute myelogenous leukemia (AML), and with vincristine (VCR) and prednisolone (PSL) for acute lymphocytic leukemia (ALL). KRN8602 was given at a dose of 12 or 15 mg/m2 for 5 consecutive days, Ara-C at a dose of 100 mg/m2 for 7 consecutive days, VCR 1.4 mg/m2 (max. 2.0 mg/body) weekly for 4 weeks, and PSL 40 mg/m2 for principally 28 consecutive days. Of 14 patients with relapsed or refractory leukemia entered in the study, thirteen patients were evaluable for safety and 12 were evaluable for response. In AML, there was 1 partial response (PR) in 4 patients at a dose of 12 mg/m2. Against 1 complete response (CR) and 3 PRs in 4 patients at a dose of 15 mg/m2. In ALL, there was 1 PR in 1 case at a dose of 12 mg/m2, and 1 CR and 2 PR in 3 at a dose of 15 mg/m2. Major toxicities were nausea/vomiting and anorexia, but incidences and grades of toxicities were not dose-dependent, and all toxicities were tolerable and manageable. From these results it is concluded that the optimal dose of KRN8602 is 15 mg/m2 for 5 consecutive days in combination with Ara-C for AML, and with VCR and PSL for ALL. PMID- 9987505 TI - [A combination of low-dose carboplatin (CBDCA) and radiation therapy in head and neck cancer patients--response and hematologenic toxicity]. AB - A combination of carboplatin (CBDCA) and radiation therapy was performed in patients with head and neck cancer. The intravenous administration of CBDCA at a weekly dose of 100 mg/body was combined with external irradiation at a dose of 1.8 Gy/day x 5/week during the same therapy period. We evaluated the effects of this method not only on survival and neoadjuvant chemotherapy in patients with advanced cancer but also on local control and prevention of distant metastases in patients with early cancer. The subjects consisted of 31 patients with head and neck cancer who visited the Department of Otolaryngology, Showa University Hospital, Kanto Rosai Hospital and Yokohama Rosai Hospital between March 1993 and March 1995. Squamous cell carcinoma was found in all but one patient who had adenocarcinoma in the parotid gland. The patients were 27 males and 4 females ranging between 40 and 81 years of age (mean, 59 years). Twenty-six patients had previously untreated tumor, while 5 patients had recurrent tumor. The clinical stage was Stage I in 6, Stage II in 10, Stage III in 5 and Stage IV in 10 patients. The original site of cancer was the larynx in 9, hypopharynx in 6, nasopharynx in 6 and elsewhere in 10 patients. The combined therapy was repeated for 2-9 courses (mean, about 5 courses). The total dose of CBDCA was 500 mg on average with a maximum of 900 mg. The total effective rate of the combined therapy was 93.3% with 12 cases of complete response (CR) and 16 cases of partial response (PR). The effective rate in patients with previously untreated tumor was 92% because one patient showed a minor response (MR) and one patient showed no change (NC). The effective rate in patients with recurrent tumor was 100%. Concerning the clinical stage, all patients with Stage I-III disease showed CR or PR, while MR was found in 1, NC in 1 and progressive disease (PD) in 1 of 10 patients with Stage IV disease, resulting in an effective rate of 71.4%. There were no CRs in Stage IV patients. Therapy was terminated due to side effects in 2 patients. Excellent safety was confirmed by laboratory data. PMID- 9987506 TI - [Late phase II clinical study of RP56976 (docetaxel) in patients with advanced/recurrent head and neck cancer]. AB - A late phase II clinical study of RP56976 (docetaxel), a new anticancer agent for advanced/recurrent head and neck cancer, was conducted in 29 institutions all over Japan as a multi-institutional cooperative study. Docetaxel was administered by 1 to 2-hour intravenous infusion at a dose of 60 mg/m2 every 3 to 4 weeks. Of 63 patients eligible in this study, 59 were judged as complete cases. Complete response (CR) was observed in 1 patient, partial response (PR) in 13, no change (NC) in 25, and progressive disease (PD) in 20, for an overall response rate of 22.2% (14/63, 95% CI: 12.7-34.5%) in eligible cases, and 23.7% (14/59, 95% CI: 13.6-36.6%) in complete cases. Previously treated patients showed a 17.9% (10/56) response rate, whereas treatment--naive patients showed a 57.1% (4/7) response rate. Among 46 patients who received prior chemotherapy, one CR and 7 PR were observed with a 17.4% response rate. Major hematological toxicities were leucopenia in 95.1% (> or = grade 3, 59.7%) and neutropenia in 90.3% (> or = grade 3, 79.0%). Other severe toxicities (> or = grade 3) included anorexia in 9.7% (6 cases), diarrhea in 3.2% (2 cases), dyspnea in 3.2% (2 cases), and fatigue in 3.2% (2 cases). One patient had a grade 3 interstitial pneumonia; however, symptoms were resolved by the administration of corticosteroids. During this study, one patient died due to multiple organ failure (MOF) caused by disseminated intravascular coagulation (DIC), and this case was reported as a therapy-related death. Based on these results, docetaxel is an active agent for treatment of head and neck cancer. PMID- 9987507 TI - [Clinical studies of oral antiemetic drugs on delayed emesis induced by cancer chemotherapy]. AB - The effects of oral antiemetic drugs on delayed emesis induced by emetogenic chemotherapy were studied in seventeen patients (43 courses) with gynecological malignancies. On day 1, all patients received intravenous granisetron (40 micrograms/kg) and methylprednisolone (250 mg/body) for the control of acute emesis 0-24 hrs after receiving CDDP or CBDCA. Then they received each oral maintenance drug (dexamethasone 4 mg/day, ondansetron 4 mg/day and metoclopramide 40 mg/day) for the control of delayed emesis from day 2 to day 5. Efficacy rates for delayed emesis were 82.4% in dexamethasone, 75.0% in metoclopramide and 50.0% in ondansetron. The complete response for delayed nausea was 88.5% in metoclopram ide, and the complete response for delayed anorexia of 64.7% in dexamethasone was higher than for other oral drugs. The results suggest the usefulness of oral antiemetic therapy of dexamethasone plus metoclopramide or ondansetron for delayed emesis induced by cancer therapy. PMID- 9987508 TI - [Effect of ondansetron hydrochloride injection and tablet against nausea and vomiting in lung cancer patients receiving carboplatin]. AB - We investigated the efficacy of combination of ondansetron hydrochloride injection and tablet against nausea and vomiting in 22 lung cancer patients (total number of chemotherapy courses: 23) receiving chemotherapy of single-dose carboplatin (CBDCA) at a dose of 302.2 +/- 31.9 mg/m2. For suppressing emesis, the patients were given 4 mg of ondansetron injection on the day of CBDCA injection (Day 1), and 4 mg/day of ondansetron tablet for Days 2 to 5. The following results were obtained 5 days after the administration of carboplatin. 1) Control of nausea graded 'Good' or better counted for 95% or higher of all cases for each day of the chemotherapy. A complete nausea suppression rate was seen in 91.3%, 81.0%, 71.4%, 63.6% and 71.4% from Day 1 to Day 5, respectively. 2) Control of vomiting graded 'Major' control or better was achieved in 95% or more of all cases, for each day. The complete vomiting suppression rate observed from Day 1 to Day 5 was 91.3%, 78.3%, 65.2%, 69.6% and 91.3%, respectively. 3) Inhibitory effect on nausea and vomiting for each day of Days 1 to 5 graded as 'Effective' or better was shown in 90% or higher of all cases; based on overall judgement for Days 1 to 5, all cases were graded as 'Effective' or better. 4) The proportion of cases which was evaluated as 'Can eat most of the meal' was 88.0%, 73.9%, 50.7%, 50.7% and 65.2% from Days 1 to 5, respectively, against 95.7% prior to the start of chemotherapy. 5) No adverse drug reaction or abnormal clinical laboratory values were seen along with ondansetron. 6) In conclusion, combined treatment with ondansetron injection and tablet was considered clinically useful in control of nausea and vomiting during administration of carboplatin, and may also be useful for out-patient chemotherapy. PMID- 9987509 TI - [Accuracy of clinical prediction of survival for terminally ill cancer patients]. AB - Accurate estimation of survival is vital for effective palliative care. To verify the value of clinical prediction of survival (CPS), a prospective study was performed on 150 terminally ill cancer patients. The CPS was highly correlated with actual survival (AS), but the accuracy was not significantly superior to the prediction by performance status alone. Serious pessimistic error, defined as AS was at least 28 days and twice as long as CPS, was recognized in 13%, while serious optimistic error, defined as AS was less than 28 days and half as long as CPS, in 15%. The frequency of serious error was not significantly different by physicians' experiences, patients' age, sex, primary disease, and metastatic locations, but was significantly higher in cases with better performance status. Also, unexpected changes resulting in death were experienced in 42% of another 186 cases. The main underlying causes were pneumonia, bleeding, heart failure, intestinal perforation, cerebrovascular disease, hepatic/renal failure, hypoglycemia, sepsis and electrolyte imbalance. Clinical prediction was not sufficiently reliable and must be further improved. PMID- 9987510 TI - [Outpatient chemotherapy with oral UFT (tegafur and uracil) and cisplatin against metastatic non-small cell lung carcinoma--an effective case]. AB - A 64-year-old man underwent a left pneumonectomy for squamous cell carcinoma of the left lung in July 1995. In May 1996, right pelvic bone metastasis occurred and was well controlled by the concurrent chemoradiotherapy; UFT (600 mg/body, day 1-14) and cisplatin (80 mg/m2, day 8) with a total 50.4 Gy of irradiation. In August 1996, left renal metastasis occurred, but regressed after two cycles of combination chemotherapy with UFT and cisplatin. In January 1997, multiple lung metastasis occurred. In accordance with the patient's request, combination chemotherapy was performed at the outpatient clinic. UFT (250 mg/m2) was given orally every day while cisplatin (60-80 mg/m2), fractionated in 3 or 5 days, was intravenously administered at an interval of 4 weeks or longer. The patient has continued the treatment for one year without serious (G3, 4) adverse events. During the treatment, the tumor growth was slow with a repeated cycle of progression and regression. The outpatient chemotherapy using UFT and cisplatin is considered to be useful, especially for the better quality of life of patients. PMID- 9987511 TI - [A case of multiple early gastric cancer showing complete response to UFT-E after endoscopic mucosal resection]. AB - A 78-year-old male underwent endoscopic mucosal resection for early gastric cancer (type II a) in the anterior wall of antrum. Follow-up endoscopy showed another early gastric cancer (type II c) in the posterior wall of cardia. He refused an operation. UFT-E 300 mg/day has been administered daily since then. After 6 months, a complete tumor response was observed. The patient has been in good health without any sign of relapse for 14 months after achievement of the complete response. PMID- 9987512 TI - [Effect of combination chemotherapy with mitomycin C and cisplatin on advanced gastric carcinoma]. AB - A 71-year-old male with advanced gastric carcinoma with paraaortic lymph node metastases underwent distal gastrectomy. Cisplatin (CDDP) 50 mg/body was administered intravenously (i.v.) on day 1 followed by the administration of 5 fluorouracil 500 mg/body/day i.v. on day 2 through day 7. After two courses of this regimen, further enlargement of paraaortic lymph nodes was revealed by CT scan, and chemotherapy was suspended. Multiple liver and lung metastases were diagnosed 6 months after initial diagnosis, and mitomycin C (MMC) 10 mg/body i.v. was administered on day 1 followed by CDDP 50 mg/body i.v. on day 2. After three courses of this regimen, partial response of the liver metastases and complete response of the lung metastases were observed, and the general condition was markedly improved without any adverse effect except slight nausea. Though the patient died of brain metastases one year after initial diagnosis, the combination chemotherapy with MMC and CDDP was nevertheless thought to improve his quality of life. PMID- 9987513 TI - [A case of small cell carcinoma of the stomach with multiple liver and lung metastases successfully treated by combined chemotherapy with cisplatin and etoposide]. AB - We experienced a case of small cell carcinoma of the stomach in which chemotherapy had been markedly effective. A 54-year-old man was admitted to our hospital complaining of hematemesis. Gastric endoscopy showed a type 2 tumor at the lesser curvature of the cardia of the remnant stomach. Total gastrectomy, splenectomy and D2 lymph node dissection were performed. Histopathologically, the tumor was diagnosed as a small cell carcinoma with findings of t 2 n 1 in stage II, and conclusive curability was A. A month after the operation, CT-scan revealed multiple liver and lung metastases, so the patient was treated by combined chemotherapy with cisplatin and etoposide called PVP for three courses every four weeks for small cell lung cancer, which resulted in remarkable reduction of metastases (96% in the liver and 81% in the lung). This result suggests that PVP chemotherapy is effective in the treatment of small cell carcinoma of the stomach as well as the lung. PMID- 9987514 TI - [A case of unresectable pancreatic cancer responding to MTX/5-FU sequential therapy]. AB - A 66-year-old woman was admitted to our hospital complaining of abdominal pain and jaundice. Upper gastrointestinal series and computed tomography revealed pancreatic cancer. Pancreatectomy could not be performed because of portal invasion and multiple liver metastasis. Cholecystectomy, choledochojejunostomy and gastrojejunostomy were performed. The patient was treated with methotrexate (MTX) 100 mg/m2 i.v. followed one hour later with 5-fluorouracil (5-FU) 700 mg/m2. Leucovorin rescue of 10 mg po was given 24 hours after MTX administration. Treatment was repeated every 14 days. As a result, the size of a primary tumor of the pancreas was reduced (42%) on computed tomography, and the CEA level decreased to 27.8 ng/ml from 84 ng/ml. No side effects were observed. The patient continued to receive chemotherapy at our outpatient clinic for 20 months. She died of exacerbation of carcinomatous peritonitis 23 months after initial admission. Therefore, we conclude that MTX/5-FU sequential therapy seems beneficial to manage advanced pancreatic carcinoma from the viewpoint of antineoplastic activity as well as quality of life. PMID- 9987515 TI - [Outline of tumor invasion and metastasis]. AB - Analysis of cancer genes and studies of cell growth, apoptosis and immortalization have shed light on how normal cells transform into malignant cancer cells. In addition, our knowledge of the molecular mechanisms by which cancer cells invade and traverse tissues and form distant metastases has been improved greatly. Several new therapeutic methods have been developed based on these new findings, and they are expected to provide patients with better choices. PMID- 9987516 TI - [Interventional trial for cancer prevention]. AB - In cancer prevention studies, the methodology of the observational study (case control study, cohort study) and interventional study were introduced. We established a protocol for an interventional randomized controlled trial for prevention of colorectal cancer. The subjects were 200 patients with multiple colorectal tumors (adenoma and/or early cancer). Two regimens were formulated for prevention of colorectal cancer. One was dietary guidance alone (Regimen I), and the other was dietary guidance plus the eating of wheat bran biscuits (Regimen II). The main end point of the trial is recurrence of colorectal tumors after 2 and 4 years. During the 4 years, 115 patients were recruited for Regimen I and 116 patients for Regimen II who agreed to participate in this trial. PMID- 9987517 TI - [Significance and problems of quality-of-life assessment in clinical trials]. AB - The importance of quality of life (QOL), as an outcome variable of cancer treatments, has rapidly become recognized not only in western countries but also in Japan. However, many problems remain to be resolved for QOL assessment methods. In this paper, we give outlines for the position of QOL as an outcome variable, the standpoint and purpose for QOL assessment, the appropriate range of QOL domains to be assessed, and the appropriate QOL measures. Furthermore, we introduce key points for the success of QOL assessment in clinical trials, the appropriate way to deal with missing data and appropriate methods for analysis in longitudinal studies. PMID- 9987518 TI - [Development of QOL questionnaires in Japan]. AB - As the QOL questionnaires used for the field of clinical oncology in Japan, there are Japanese versions of the Functional Living Index Cancer (FLIC), WHOQOL, Functional Assessment of Cancer Therapy Scale (FACT) and European Organization for Research and Treatment of Cancer QLQ-C 30 (QLQ -C30). We also have the QOL Questionnaire for Cancer Patients Treated with Anticancer Drugs (QOL-ACD), which was originally developed in Japan. In this review, their characteristics, and the topics in their validation process are presented. Finally, the issues of cross cultural validation, metric equivalence of scoring between countries, and data missing in clinical study are also discussed. PMID- 9987519 TI - [Review process of new oncology drug application in Japan--role of MD reviewer]. AB - On the basis of discussion by the Committee for Drug Safety Ensuring Measures, the Japanese Ministry of Health and Welfare (MHW) has amended the Pharmaceutical Affairs Law and related laws, and is reforming its review system for approving new drugs. One of the most important changes in the review system is the establishment of Pharmaceuticals and Medical Devices Evaluation Center (PMDEC) in July, 1997 under the National Institute of Health Sciences, a research institute under MHW. PMDEC, the Evaluation and Licensing Division at MHW and the Organization for Drug ADR Relief, R&D Promotion and Product Review (the Drug Organization) are in charge of drug approval, and reexamination and reevaluation applications. Before the reform new drug application reviews had been conducted mainly by the Central Pharmaceutical Affairs Council (CPAC). After the reform PMDEC, employing technical officials who have expertise in pharmacology, toxicology, biostatistics, clinical medicine, or other scientific fields, jointly review the applications with CPAC. The Evaluation and Licensing Division takes charge of administrative matters, such as final decisions on approvals, developing guidelines concerning the review process, international affairs, and regulatory instructions. During the early part of review the Drug Organization conducts a compliance review on the documents, which a sponsor submits with the approval application, and GCP inspection. PMID- 9987520 TI - [Current issues and perspectives in Japan Clinical Oncology Group]. AB - Clinical trials can be classified either as "sponsored trials (sponsored by industries)" or "non-sponsored trials (funded by government etc.)". The former is for the application of the commercialization/import of new drugs by the government, and the latter basically seeks to establish and improve the "State of the Art" of medical treatments/prevention in certain disease fields. We present an overview of the Japan Clinical Oncology Group (JCOG), which is a cooperative group funded by government for conducting non-sponsored cancer clinical trials, and the fundamental procedures managed by our JCOG Data Center. The problems and difficulties concerning data management in our trials, our roles and limitations as a non-commercial data coordinating center, future perspectives and issues on local data management are also discussed. PMID- 9987521 TI - [Present situation and future subjects of N.SAS study--based on experience of managing data center]. AB - The "National Surgical Adjuvant Study" (N-SAS) was established as a study group on carcinostatics on the market as part of the Ministry of Health and Welfare's 1995/1996 consignment project. Patient registration started in October 1996, and later it was restructured as a consignment study by Taiho Pharmaceutical Co., Ltd. in April 1997. It still continues to date. EPS Co., Ltd. has operated the "N.SAS Data Center" to conduct three clinical trials of N.SAS study. In the following, we analyse the current situation and subjects of N.SAS study from the viewpoint of the data center, recognising the necessity of infrastructure at medical institutions while complying with enforcement of newly GCP and GPMSP. First, the organization and function of N.SAS, and the role and position of data center on N.SAS study, are explained. Some notes are introduced from conducting In-house Monitoring on N.SAS, especially methods and formation of communicating information between N.SAS Data Center and institutions. We also propose an infrastructure which will be essential for smooth promotion of long-term and large-scale trials like the N.SAS study. PMID- 9987522 TI - [Clinical studies conducted in the U.S]. AB - There are many things that we can learn from the clinical trials conducted in the U.S. They move ahead based on explicit basic principles regarding various matters such as the method for setting up the clinical trial system, selection of CRO, selection of investigators, monitoring activities that are mainly based on their direct access to source documents and sponsor's action when a lack of compliance with GCP occurs. The matters newly introduced in the Japanese new GCP have already been put into practice in the U.S. It is evident that compliance with these standards is ensured in the U.S. by the activities of study coordinators who take greater part in the clinical studies themselves. In order to expedite introduction of the study coordinator system in Japan even just a little, sponsors should consider providing medical institutions with relevant information as well as a chance to educate and train their study coordinators to optimize the function. PMID- 9987523 TI - [Improving the infrastructure for clinical trials in Japan]. AB - It is necessary for us to reform the infrastructure for clinical trials in Japan in this new GCP era. Medical institutions for clinical trials should prepare to implement monitoring and auditing procedures for quality control and quality assurance of clinical trials. It is also necessary to ease the burden and improve the benefits of participating in clinical trials by subjects. Although there has been no effort to educate and train CRC/SC staff at all in Japan, future improvement in this area is needed to bring the quality of Japan's clinical trials up to international standards. PMID- 9987524 TI - [Roles of nurses in clinical trials of anticancer drug development]. AB - In Japan nurses were not much involved in clinical trials in connection with new drug development in the field of cancer nursing in the past for the following reasons: 1) systems for cooperations among different services in hospital were not well established. 2) There was a lack of information about the drugs from physicians, 3) It was difficult to obtain informed consent from patients. In the new GCP system of Japan started last April in accordance with ICH-GCP, persons who support patients and assist physician investigators are desperately needed to maintain QA and QC of the clinical trials. Research nurses are the most suitable persons to fulfill such positions. The roles of research nurses in these settings are patient care, coordinator, data collecting and educator in the new system. PMID- 9987525 TI - [Need to establish academic research organization for cancer clinical trial and clinical research system having clinical investigators and study coordinators, with special reference to promotion of medical and life science research policy]. AB - There are two types of cancer clinical trials in Japan. One is the therapeutic trial sponsored by a pharmaceutical company for approval of clinical use of new anticancer agent, and another is the clinical trial sponsored by an investigator for establishment of standard state-of-the-art therapy. Advances in cancer chemotherapy can not be achieved without active use of both types of cancer clinical trial. However, the infrastructure, such as academic research organization for cancer clinical trials and clinical research systems having clinical investigators and study coordinators, has not been sufficiently established. New GCP and the Drugs, Cosmetics and Medical Instruments Act are applied only to the therapeutic trials sponsored by pharmaceutical companies, but not to clinical trials sponsored by investigators. There is no National Research Act to cover both types of clinical trial. In this paper, the problems mentioned above are summarized, and a proposal to solve these problems is presented. The Medical and Life Science Research Policy of the Japanese Government should be improved to promote both basic and clinical research. The promotion of clinical research is essential for improvement in the quality of medical practice, appropriate changes in the medical security system, and activation of pharmaceutical science. PMID- 9987527 TI - The Mayo Clinic gamma knife experience: indications and initial results. AB - OBJECTIVE: To review the results and expectations of contemporary stereotactic radiosurgery. MATERIAL AND METHODS: We conducted a retrospective analysis of 1,033 consecutive patients who underwent gamma knife radiosurgery at Mayo Clinic Rochester between January 1990 and January 1998. RESULTS: The number of patients undergoing radiosurgery increased from 57 in 1990 to 216 in 1997. Of 97 patients with arteriovenous malformations who underwent follow-up angiography 2 years or more after a single radiosurgical procedure, 72 (74%) had complete obliteration of the vascular malformation. Of 209 patients who underwent radiosurgery for benign tumors (schwannomas, meningiomas, or pituitary adenomas) and had radiologic studies after 2 years or more of follow-up, tumor growth control was noted in 200 (96%). Tumor growth was also controlled in 90% of brain metastatic lesions at a median of 7 months after radiosurgery. Of 20 patients with trigeminal neuralgia and follow-up for more than 2 months, 14 (70%) were free of pain after radiosurgery. CONCLUSION: Radiosurgery is a safe and effective management strategy for a wide variety of intracranial disorders. Use of radiosurgical treatment should continue to increase as more data become available on the long-term results of this procedure. PMID- 9987528 TI - Congenitally bicuspid aortic valves: a surgical pathology study of 542 cases (1991 through 1996) and a literature review of 2,715 additional cases. AB - OBJECTIVE: To describe a clinicopathologic study of a large group of congenitally bicuspid aortic valves surgically excised at a single institution. MATERIAL AND METHODS: The medical charts and bicuspid valves from patients undergoing aortic valve replacement at Mayo Clinic Rochester between 1991 and 1996 were retrospectively reviewed. RESULTS: The age of the 542 patients ranged from 1 to 86 years (mean, 61), and 372 (69%) were men. Among these, 409 (75%) had pure aortic stenosis (AS), 73 (13%) had pure aortic insufficiency (regurgitation) (AI), 53 (10%) had combined AS and AI, and 7 (1%) had normal function. The mean age was higher for those with AS than AI (65 versus 46 years; P < 0.001), whereas the male-to-female ratio was higher for AI than AS (17.3:1 versus 1.7:1; P < 0.001). The two cusps were not equal in size in 95%, and a raphe was present in 76% (67% typical, 9% atypical). Raphal position was described in 315 and was between the right and left cusps in 270 (86%). Raphal absence occurred more often in valves with equal-sized cusps than unequal (33% versus 14%; P = 0.005). Moderate to severe calcification affected valves with AS more frequently than AI (99% versus 41%; P < 0.001). In contrast, annular dilatation was associated with AI more than AS (48% versus 11%; P < 0.001). Acquired commissural fusion involved valves with combined AS and AI more often than the other functional states (31% versus 14%; P = 0.002). Sixteen patients (age range, 18 to 78 years; 13 men) had infective endocarditis (6 active, 10 healed), including 10 with AI (9 men), 3 with AS plus AI, 2 with AS, and 1 with normal function but embolization. CONCLUSION: Functionally, the most common fate of congenitally bicuspid aortic valves was calcific stenosis with or without regurgitation (85%). Because approximately 4 million US citizens have bicuspid valves and because valve replacement is currently the only treatment of symptomatic AS, this disorder will continue to affect health-care costs. PMID- 9987529 TI - Radiation-induced pneumonitis in the "nonirradiated" lung. AB - OBJECTIVE: To describe six cases of radiation-induced organizing pneumonitis occurring outside the direct radiation field and to review clinical, radiologic, and histologic aspects of this entity. MATERIAL AND METHODS: We present detailed case reports of six women, with a mean age of 62.8 years (range, 50 to 75), who had received radiation therapy (mean dose, 6,560 cGy) for breast cancer. RESULTS: From 6 to 17 months (mean, 8.8) after the completion of radiotherapy, recurrent and migrating lung infiltrates were detected outside the radiation field in the six study patients. Three patients had pronounced respiratory symptoms, whereas the rest were minimally symptomatic or asymptomatic. Thoracic computed tomography showed dense alveolar infiltrates. Bronchoalveolar lavage in two patients revealed lymphocytosis (25% and 19%), and lung biopsy in five patients demonstrated a histologic pattern consistent with bronchiolitis obliterans organizing pneumonia. Even though the symptomatic patients showed prompt resolution of their symptoms and roentgenographic abnormalities after systemic corticosteroid therapy, the lung infiltrates recurred after corticosteroid therapy was discontinued. CONCLUSION: These six cases, including their prompt response to corticosteroid therapy, provide additional evidence that irradiation damages lung tissue outside of the direct treatment field and suggest that an immunologically mediated lymphocytic alveolitis may be responsible for the recurrent migratory organizing pneumonitis. PMID- 9987530 TI - Long-term results of laparoscopic splenectomy for immune thrombocytopenic purpura. AB - OBJECTIVE: To assess the results of laparoscopic splenectomy as a treatment for immune thrombocytopenic purpura (ITP). MATERIAL AND METHODS: We conducted a retrospective study of all patients who underwent laparoscopic splenectomy for ITP at our institution between August 1992 and May 1997. RESULTS: Of 27 patients who underwent attempted laparoscopic splenectomy for ITP at our institution during the study period, 26 had completion of the procedure without conversion to an open splenectomy. The median postoperative hospital stay was 1.5 days, and no postoperative deaths occurred. In one patient, pancreatitis developed postoperatively. In four patients, splenectomy failed--two initially and two subsequently--and reinstitution of medical therapy was necessary. The other patients have remained free of medication, and 19 patients have platelet counts greater than 100 x 10(9)/L. The 3-year actuarial success rate was 81.5%. Response to corticosteroid therapy preoperatively may be an indicator of success of splenectomy. CONCLUSION: Laparoscopic splenectomy is safe and allows prompt recovery. Long-term response rates are similar to those achieved with open splenectomy. PMID- 9987531 TI - Use of patient-centered function and symptom rating systems in spinal disorders. AB - The criteria for assessing patients with disorders of the lumbar spine have historically been subjective and variable. This situation has led to uncertainty about diagnostic criteria, operative indications, and surgical outcome. In an effort to improve the evaluation process, various patient-centered function and symptom rating systems, including questionnaires and functional tests, have recently been developed. This report reviews several of these rating systems and their role in the assessment of patients with back-related symptoms. PMID- 9987532 TI - Rapidly growing mycobacterial lung infection in association with esophageal disorders. AB - Esophageal or other swallowing disorders complicated by lipoid pneumonia are reported to be associated with pulmonary infections caused by rapidly growing mycobacteria. Herein we describe a 63-year-old woman with achalasia of the esophagus complicated by lung infection with Mycobacterium chelonae and a 47-year old man in whom long-term ingestion of mineral oil was complicated by lipoid pneumonia and M. fortuitum lung infection. A MEDLINE search of English language publications from 1966 to 1997 revealed 18 cases of lung infections caused by rapidly growing mycobacteria in patients with esophageal disorders. Of these 18 patients and our 2 patients, 11 were men and 9 were women (mean age, 50 years). Achalasia was present in 11 patients, and 6 had lipoid pneumonia without evidence of esophageal disorders. Three patients had lipoid pneumonia caused by lipoid ingestion in the setting of achalasia or another swallowing disorder. In 14 patients, lung infection was caused by M. fortuitum; in 5, M. chelonae; and in 1, a non-M. fortuitum rapidly growing mycobacterial infection. The most common clinical feature was fever, and the most common roentgenologic abnormality was the presence of unilateral or bilateral and patchy or dense infiltrates. The sputum was the most common source of isolation of rapidly growing mycobacteria. Achalasia and lipoid pneumonia are important risk factors for the development of lung infections caused by rapidly growing mycobacteria. Treatment of the esophageal disease might prevent occurrence of and facilitate recovery from these infections. PMID- 9987533 TI - Recrudescence of treated neurosyphilis in a patient with human immunodeficiency virus. AB - The natural history of syphilis has been altered by the human immunodeficiency virus (HIV) epidemic. Treatment of patients coinfected with syphilis and HIV is currently controversial; progression and relapse of neurosyphilis have been reported. This case report documents failure of primary treatment and neurosyphilitic recrudescence. In a 32-year-old HIV-positive woman with syphilis who had no additional sexual contacts, the disease progressed to neurosyphilis despite three intramuscular doses of penicillin. After extended intravenous penicillin treatment, neurosyphilis later recurred and re-treatment was necessary. Because many urban centers are affected by high rates of sexually transmitted diseases, including common coinfections of syphilis and HIV, further efforts should be made to identify subsets of patients who may be at high risk of syphilitic recrudescence. PMID- 9987534 TI - Gradually progressive dementia without discrete cerebrovascular events in a patient with Sneddon's syndrome. AB - A 37-year-old man sought medical advice because of an 8-year history of a slowly progressive dementing illness with no clinically apparent discrete strokelike episodes. Cognitive functioning was markedly, globally impaired without lateralizing or localizing features. Widespread livedo reticularis led to a diagnosis of Sneddon's syndrome. Antiphospholipid antibodies and lupus anticoagulant were negative. Magnetic resonance imaging showed widespread cerebral atrophy, cortical and subcortical cerebral infarcts, and extensive periventricular white matter abnormalities. Cerebral angiography revealed diffuse medium- and small-vessel occlusive disease, with numerous collaterals in the mid and distal circulation but no evidence of atherosclerosis or vasculitis. No other cause of a dementing illness was found. We postulate that our patient's dementia was due to the cumulative effects of multiple cerebral infarcts. PMID- 9987535 TI - Primary pulmonary melanoma: case report and literature review. AB - Primary pulmonary melanoma is a very rare disease, with only 19 cases previously reported in the English language literature. These cases suggest that melanoma can arise in the lung as a primary tumor, probably from residual melanoblasts. Primary pulmonary melanoma is frequently endobronchial and often manifests with symptoms of cough, hemoptysis, and lobar collapse. Aggressive surgical resection, irrespective of lymph node involvement, offers possible long-term survival in some patients. The diagnosis of primary pulmonary melanoma necessitates that both clinical and histologic criteria be fulfilled. Herein diagnostic criteria are proposed, and the diagnostic approach is discussed. PMID- 9987536 TI - Otto Meyerhof--Nobel Prize for studies of muscle metabolism. PMID- 9987537 TI - Life-threatening rashes: dermatologic signs of four infectious diseases. AB - Four infectious diseases that are associated with high rates of morbidity and mortality are Rocky Mountain spotted fever, meningococcal disease, staphylococcal toxic shock syndrome, and streptococcal toxic shock syndrome. These diseases necessitate a timely diagnosis and treatment, which may be facilitated by recognition of the characteristic cutaneous findings. Herein the clinical manifestations, diagnosis, and management are presented, with emphasis on the dermatologic signs of each disease. A dermatology consultation can be valuable, but all physicians should be familiar with the cutaneous findings of these potentially life-threatening diseases. PMID- 9987538 TI - 73-year-old woman with weakness and falls. PMID- 9987539 TI - Antifungal agents. Part II. The azoles. AB - Before 1978, amphotericin B and flucytosine were the only drugs available for the treatment of systemic fungal infections. The imidazoles, miconazole and ketoconazole, were introduced during the next 3 years. Intravenously administered miconazole served a limited therapeutic role and is no longer available. Orally administered ketoconazole, an inexpensive, effective, and convenient option for treating mucosal candidiasis, was widely used for a decade because it was the only available oral therapy for systemic fungal infections. During the 1990s, use of ketoconazole diminished because of the release of the triazoles--fluconazole and itraconazole. Fluconazole is less toxic and has several pharmacologic advantages over ketoconazole, including penetration into the cerebrospinal fluid. In addition, it has superior efficacy against systemic candidiasis, cryptococcosis, and coccidioidomycosis. Despite a myriad of drug interactions and less favorable pharmacologic and toxicity profiles in comparison with fluconazole, itraconazole has become a valuable addition to the antifungal armamentarium. It has excellent activity against sporotrichosis and seems promising in the treatment of aspergillosis. Itraconazole has replaced ketoconazole as the therapy of choice for nonmeningeal, non-life-threatening cases of histoplasmosis, blastomycosis, and paracoccidioidomycosis and is effective in patients with cryptococcosis and coccidioidomycosis, including those with meningitis. Further investigation into the development of new antifungal agents is ongoing. PMID- 9987540 TI - Radiosurgery as a future part of neurosurgery. PMID- 9987541 TI - Nomenclature of "paroxysmal sympathetic storms". PMID- 9987542 TI - Patient-physician agreement on reasons for outpatient visits. PMID- 9987543 TI - Thoughts on waiting for the millennium. PMID- 9987545 TI - Use of backrest elevation in critical care: a pilot study. AB - BACKGROUND: Use of lower backrest positions occurs frequently and is a factor in the development of ventilator-associated pneumonia. OBJECTIVES: To determine the usual bed elevation and backrest position in a medical intensive care unit and their relationship to hemodynamic status and enteral feeding. METHODS: Data were collected in a 12-bed medical respiratory intensive care unit for 2 months. A protractor was used to measure the elevation of the head of the bed. Hemodynamic status was defined by systolic, diastolic, and mean arterial blood pressure measurements retrieved from each patient's flow sheet. RESULTS: The sample included 347 measurements of 52 patients. Mean backrest elevation was 22.9 degrees, and 86% of patients were supine. Backrest position differed significantly (P = .005) among nursing shifts (days, evenings, nights) but not for systolic (r = -0.04, P = .49), diastolic (r = 0.01, P = .83), or mean arterial blood pressure (r = -0.01, P = .84). Backrest elevation did not differ significantly between patients who were receiving enteral feedings and patients who were not (P = .23) or between patients receiving intermittent versus continuous nutrition (P = .22). CONCLUSIONS: Use of higher levels of backrest elevation (> or = 30 degrees) is minimal and is not related to use of enteral feeding or to hemodynamic status. The rationale for using lower backrest positions for critically ill patients may be based on convenience, the patient's comfort, or usual patterns in the unit. However, the dangers of supine positioning and its relationship to aspiration and ventilator-associated pneumonia should not be minimized. PMID- 9987544 TI - Agreement and clinical utility of 2 techniques for measuring cardiac output in patients with low cardiac output. AB - BACKGROUND: The reliability of cardiac output obtained with the bolus technique is a problem. OBJECTIVES: To compare measurements of cardiac output measured with bolus and continuous techniques in patients with low cardiac output and to determine if measurements obtained with the continuous technique increased the number of subsequent clinical decisions. METHODS: In 60 intensive care patients, a nurse recorded a single continuous cardiac output measurement and then obtained the mean of 3 consecutive bolus determinations. The medical records of these 60 patients (experimental group) for the next 48 hours and of 60 other patients with regular or mixed venous oximetry catheters (control group) were reviewed to assess the occurrence of cardiac output events and the frequency of clinical decisions based on the events. RESULTS: Mean cardiac output was 4.46 L/min by the continuous technique and 5.20 L/min by the bolus technique (P = .011) for the experimental group. Median bias between the 2 types of measurements was -0.10 L/min (P = .79). Twenty-three of the pairs (38%) had an absolute percent difference greater than 15%. Of these, 18 (78%) had a higher bolus reading. Treatment decisions per 48 hours were 9.9 for the experimental group and 8.6 for the control group (P = .014). Median length of stay was 2 days less in the experimental group (P = .02), and mean highest cardiac output was 0.81 L/min higher (P = .009). CONCLUSIONS: Measurements of cardiac output determined with the continuous technique may be more precise than measurements determined with the bolus technique. Continuous cardiac output information increases the number of treatment decisions and actions that may shorten hospital length of stay. PMID- 9987546 TI - Evidence-based practice: fever-related interventions. AB - Fever is a common phenomenon in critically ill patients. Ideally, all decisions about treatment of fever would be based on results of well-developed research studies. Instead, some research questions related to treatment of fever have been studied more extensively than others. This article is an evaluation of the usefulness of the research studies related to treatment of fever in the critically ill. Two questions are addressed: when is treatment of fever most beneficial to a critically ill patient, and how is fever most effectively treated in the critically ill? Evidence related to the treatment of fever is evaluated by using the recommendation levels of the research-based practice protocols of the American Association of Critical-Care Nurses. PMID- 9987547 TI - Therapeutic paralysis of critically ill trauma patients: perceptions of patients and their family members. AB - BACKGROUND: Neuromuscular blocking agents are used in critically ill patients to induce therapeutic paralysis. These drugs leave patients fully immobile but conscious. Analgesics and sedatives are concomitantly administered with the paralytic agents. Little is known about what patients remember when they receive these combinations of drugs. Even less is known about the experiences and needs of the patients' family members during the patients' paralysis. OBJECTIVES: To obtain recollections of therapeutic paralysis in critically ill adult trauma patients and to determine the psychological, emotional, and educational needs of the patients' family members during the time the patients were paralyzed. METHODS: A qualitative phenomenological approach was used to investigate the "lived" experience of therapeutic paralysis of 11 pairs of subjects. Each pair consisted of one critically ill adult trauma patient and one member of the patient's family. RESULTS: The patients recalled their experience of therapeutic paralysis with vagueness, as if they had been dreaming. Few recalled pain or painful procedures. Patients remembered having nurses and family members provide emotional support and encouragement. Family members understood the rationale for use of the drugs. They remembered being encouraged to touch and talk with patients. The subjects suggested providing additional education about events that occur when paralysis is being reversed. CONCLUSIONS: Two confounding variables may have affected these findings: a liberalized visiting policy and use of effective pain and sedation protocols. Healthcare professionals and patients' family members should monitor bedside conversations and use touch and words of encouragement to support patients during therapeutic paralysis. PMID- 9987548 TI - Propylene glycol toxicity related to high-dose lorazepam infusion: case report and discussion. PMID- 9987549 TI - A post hoc descriptive study of patients receiving propofol. AB - BACKGROUND: Use of propofol has recently gained popularity in intensive care settings for patients receiving mechanical ventilation. This newer intravenous sedative is often preferred over other sedatives because of a rapid onset of action, easy titration that allows neurological assessment during administration, and quick arousability of patients after the drug is discontinued. OBJECTIVES: To determine the time to awakening after discontinuance of propofol in a sample of 100 patients receiving mechanical ventilation who had received propofol for at least 12 hours. In addition, demographics, primary and secondary diagnoses, clinical signs and symptoms, propofol dosage and duration, and concomitant use of analgesics and sedatives were determined. METHODS: A descriptive post hoc design was used. Patients' medical records for an 18-month period in an urban hospital in the southwestern United States were reviewed. Sections used for data collection included each patient's admission sheet, the findings of the history and physical examination done by a physician, physicians' progress notes, nursing notes, critical care flow sheets, and records of medications administered. RESULTS: Although nursing documentation indicated 2 common side effects, decreases in heart rate (18%) and decreases in systolic blood pressure (17%), within the first hour of treatment with propofol, immediate arousability after the drug was discontinued was not observed. Mean Glasgow Coma Scale scores took longer than 30 minutes to return to baseline. CONCLUSIONS: The awakening time of patients receiving propofol for a protracted period, usually in conjunction with other potentiating drugs, may be longer than is commonly cited in the literature. PMID- 9987550 TI - Advance directives: the emerging body of research. AB - BACKGROUND: With the passage of the Patient Self-Determination Act in 1990, new procedures and documents became available for planning end-of-life care. These new procedures and documents are now being examined scientifically. OBJECTIVE: To review existing research on the use of advance directives. DATA SOURCES: Computer search using Grateful Med software from the National Library of Medicine with MEDLINE and BIOETHICSLINE databases. STUDY SELECTION: Studies that showed an emerging consensus or reported vastly differing results were selected. Selected studies examined these specific areas: demographic data on patients with advance directives, completion rates, capacity to complete, patients' preferences, stability of patients' decisions over time, treatment choices, proxy decision makers, treatment provided, and cost. RESULTS: The body of important research about advance directives is growing. A profile of their clinical utility is emerging. CONCLUSIONS: The research done so far can stimulate future research and can begin to suggest possible changes in practice. However, the body of research is not yet large enough or well controlled enough to answer conclusively many of the questions about planning of end-of-life care. PMID- 9987551 TI - Low-molecular-weight heparin: an antithrombotic agent whose time has come. AB - LMWH (enoxaparin) should be used in combination with aspirin in the early phase of non-Q wave MI and in patients with unstable angina. The benefit of LMWH in acute coronary syndromes has been validated in several clinical trials. In addition, the use of LMWH is cost-effective when compared with use of UFH. The incidence of minor bleeding may be greater with LMWH than with UFH, most frequently due to ecchymosis at the injection site. However, the frequency of major bleeding did not differ between the two heparins. LMWH has been used successfully for the past 4 years by orthopedic surgeons in the prevention of pulmonary emboli. LMWH should replace UFH in the management of acute coronary syndromes. PMID- 9987552 TI - Health care professionals caring for critically ill patients. PMID- 9987553 TI - Improvement of end-of-life care. PMID- 9987554 TI - Case-control study of mesothelioma in South Africa. AB - BACKGROUND: South Africa has, uniquely, mined, transported, and used crocidolite, amosite, and chrysotile. A multicenter case-control study was done in South Africa to examine the details of asbestos exposure in cases and controls, and to calculate relative risks for level of certainty of asbestos exposure, nature of exposure (e.g., environmental, occupational) and fiber type. METHODS: Cases and controls (one cancer and one medical per case) were collected by six study centers from referral hospitals, and exposure information was collected by interviewing cases and controls in life. RESULTS: One hundred and twenty-three cases were accepted into the study. None had purely chrysotile exposure. Twenty three cases had mined Cape crocidolite; three had mined amosite; and three Transvaal crocidolite plus amosite. A minimum of 22 of the cases had exclusively environmental exposure, 20 were from the NW Cape crocidolite mining area. The relative risks associated with environmental exposure in the NW Cape (crocidolite) were larger than for environmental exposure in the NE Transvaal (amosite and crocidolite): 21.9 vs. 7.1 and 50.9 vs. 12.0 for the cancer control and medical control datasets, respectively. CONCLUSIONS: The results confirm the importance of environmental exposure in the Cape crocidolite mining area, the relative paucity of cases linked to amosite, the rarity of chrysotile cases and are consistent with a fiber gradient in mesotheliomagenic potential for South African asbestos with crocidolite > amosite > chrysotile. PMID- 9987555 TI - An evaluation of proposed frameworks for grouping polychlorinated biphenyl (PCB) congener data into meaningful analytic units. AB - BACKGROUND: Polychlorinated biphenyls (PCBs) have been associated with a variety of health outcomes. Enhanced laboratory techniques can provide a relatively large number of individual PCB congeners for investigation. However, to date there are no established frameworks for grouping a large number of PCB congeners into meaningful analytic units. METHODS: In a case-control study of serum PCB levels on breast cancer risk, measured levels of 56 PCB congener peaks were available for analysis. We considered several approaches for grouping these compounds based on 1) chlorination, 2) factor analysis, 3) enzyme induction, 4) enzyme induction and occurrence, and 5) enzyme induction, occurrence, and other toxicological aspects. The utility of a framework was based on the mechanism of biologic actions within each framework, lack of collinearity among congener groups, and frequency of detection of PCB congener groups in measured serum levels of 192 healthy postmenopausal women. RESULTS: Most participants had detectable levels for the proposed PCB congeners groups, using degree of chlorination as a grouping framework. In addition, the previously proposed grouping approach based on enzyme induction, occurrence, and other toxicological aspects was an applicable alternative to the crude approach of grouping by degree of chlorination. Grouping these congeners with respect to P450 enzyme induction activity, and the previously proposed framework based on enzyme induction and occurrence, did not fit these data as well, because only a small proportion of participants had detectable levels for the congener groups with the greatest toxicological potential. Statistical grouping did not result in an interpretable and meaningful clustering of these exposures. CONCLUSIONS: In these data, grouping with respect to degree of chlorination and the previously proposed framework based on enzyme induction, occurrence, and other toxicological aspects were the most useful approaches to reducing a large number of PCB congeners into meaningful analytic units. Factors affecting the utility of the proposed grouping frameworks are discussed. PMID- 9987556 TI - Clinical management of carpal tunnel syndrome: a 12-year review of outcomes. AB - Carpal tunnel syndrome (CTS) is a disorder frequently encountered by occupational health care specialists. The health care management of this disorder has involved a diverse set of clinical procedures. The present article is a review of the literature related to CTS with an emphasis on occupational-related CTS. MEDLINE, Cumulative Index to Nursing and Allied Health Literature, PsycLIT, and NIOSHTIC databases from 1985-1997 were searched for treatment outcome studies related to CTS. Treatments of interest included surgery, physical therapy, drug therapy, chiropractic treatment, biobehavioral interventions, and occupational rehabilitation. A systematic review of the effects of these interventions on symptoms, medical status, function, return to work, psychological well-being, and patient satisfaction was completed. Compared to other treatments, the majority of studies assessed the effects of surgical interventions. Endoscopic release was associated with higher levels of physical functioning and fewer days to return to work when compared to open release. Limited evidence indicated: 1) steroid injections and oral use of B6 were associated with pain reduction; 2) in comparison to splinting, range of motion exercises appeared to be associated with less pain and fewer days to return to work; 3) cognitive behavior therapy yielded reductions in pain, anxiety, and depression; and, 4) multidisciplinary occupational rehabilitation was associated with a higher percentage of chronic cases returning to work than usual care. Workers' compensation status was associated with increased time to return to work following surgery. Conclusions are preliminary due to the small number of well-controlled studies, variability in duration of symptoms and disability, and the broad range of reported outcome measures. While there are several opinions regarding effective treatment, there is very little scientific support for the range of options currently used in practice. Despite the emerging evidence of the multivariate nature of CTS, the majority of outcome studies have focused on single interventions directed at individual etiological factors or symptoms and functional limitations secondary to CTS. PMID- 9987557 TI - Latency analysis in epidemiologic studies of occupational exposures: application to the Colorado Plateau uranium miners cohort. AB - BACKGROUND: Latency effects are an important factor in assessing the public health implications of an occupational or environmental exposure. Usually, however, latency results as described in the literature are insufficient to answer public health related questions. Alternative approaches to the analysis of latency effects are warranted. METHODS: A general statistical framework for modeling latency effects is described. We then propose bilinear and exponential decay latency models for analyzing latency effects as they have parameters that address questions of public health interest. Methods are described for fitting these models to cohort or case-control data; statistical inference is based on standard likelihood methods. APPLICATION: A latency analysis of radon exposure and lung cancer in the Colorado Plateau uranium miners cohort was performed. We first analyzed the entire cohort and found that the relative risk associated with exposure increases for about 8.5 years and thereafter decreases until it reaches background levels after about 34 years. The hypothesis that the relative risk remains at its peak level is strongly rejected (P < 0.001). Next, we investigated the variation in the latency effects over subsets of the cohort based on attained age, level and rate of exposure, and smoking. Age was the only factor for which effect modification was demonstrated (P = 0.014). We found that the decline in effect is much steeper at older ages (60+ years) than younger. CONCLUSION: The proposed methods can provide much more information about the exposure-disease latency effects than those generally used. PMID- 9987558 TI - Improvement in semen quality associated with decreasing occupational lead exposure. AB - BACKGROUND: Cross-sectional studies have suggested that occupational lead exposure may adversely affect sperm quality. METHODS: Sperm quality changes were prospectively assessed in 19 men employed at a car battery plant where efforts were made to decrease the exposure level. The participants delivered monthly samples of semen and venous blood during their employment at the factory. The factory then closed, and additional samples were obtained from 16 of the men. RESULTS: Average blood-lead concentrations decreased from 2.03 mumol/l to 0.96 mumol/l during the observation period. Concomitantly, significant improvements were seen in the proportion of motile cells both at sample delivery and after 24 hr, and in penetration. However, the sperm cell concentration and the proportion of morphological abnormalities did not change. CONCLUSIONS: These results support the notion that occupational lead exposure at currently acceptable levels has a small adverse effect on sperm quality, especially sperm motility, and that this effect is at least partially reversible. PMID- 9987559 TI - Elevated mortality from nonalcohol-related chronic liver disease among female rubber workers: is it associated with exposure to nitrosamines? AB - BACKGROUND: Despite several case reports describing liver toxicity of nitrosamines and the fact that some N-nitroso compounds are used to induce cirrhosis of the liver in animal models, this association has not been investigated in epidemiological studies. METHODS: A cohort of 2,875 female rubber workers who were active on January 1, 1976, or hired thereafter, and who had been employed for at least 1 year in one of five plants producing tires or technical rubber goods was followed for mortality from January, 1976, through December, 1991. Work histories were reconstructed using routinely documented "cost center codes" and classified into six work areas. Age and calendar year standardized mortality ratios (SMR) and 95% confidence intervals (95% CI) were calculated and stratified by plant, work area, year of hire, and years of employment in the respective work area. RESULTS: The excess mortality from cirrhosis of the liver was most pronounced for nonalcohol-related cirrhosis of the liver (ICD-9 571.4 571.9: 10 deaths, SMR 202; 95% CI 97-372). Mortality from alcohol-related cirrhosis of the liver (ICD-9 571.0-571.3: 3 deaths, SMR 153; 95% CI 31-446) and from other alcohol-related diseases (organic psychoses, injury, and poisoning) was not statistically significantly elevated. All 10 cases of nonalcohol-related cirrhosis had worked in production of technical rubber goods (SMR 279; 95% CI 134 514) and risks increased with earlier years of hire and with longer duration of employment in this work area. DISCUSSION: Although our results must be interpreted with caution, they suggest that the observed excess deaths from cirrhosis of the liver are associated with occupational risk factors. In light of additional evidence from case reports and animal data, exposure to nitrosamines may be a plausible risk factor for the observed excess mortality. PMID- 9987560 TI - Nested case-control study of esophageal cancer in relation to occupational exposure to silica and other dusts. AB - BACKGROUND: Standardized proportionate mortality ratio (SPMR) was found to be 2.2 (95% CI = 1.3-3.5) for esophageal cancer (EC) among workers exposed to refractory brick dust in a large iron-steel complex in China. METHODS: A nested case-control design within a cohort of industrial workers. One hundred and twenty-five EC cases and 250 controls were identified from the death registry file. Interviews were conducted of the next of kin for past exposure information on job, domestic, and lifestyle factors. History of occupational exposure to various dusts was reconstructed from personnel files and by interviewing colleagues utilizing a job exposure matrix. RESULTS: After adjusting for confounders, occupational exposure to silica dust was the most important risk factor among all variables investigated, with a 2.8-fold risk and a clear dose-response by length of exposure. Alcohol drinking (OR = 1.8) and coal cooking (OR = 2.0) were risk factors and high consumption of fruit diet (OR = 0.5) and meat diet (OR = 0.6) were protective factors. CONCLUSIONS: The relationship between occupational exposure to silica dust and the risk of EC found in an earlier SPMR study was confirmed. Ingestion of silica particles after lung clearance may increase the risk of EC among workers exposed to silica. PMID- 9987561 TI - Tissue burden of asbestos in nonoccupationally exposed individuals from east Texas. AB - BACKGROUND: The potential for asbestos exposure among members of the general population is appreciable, considering its widespread use in many products. This study examined tissue burden of asbestos in such a population. METHODS: A group of 33 individuals who had no work history of occupational exposure to asbestos were included in the study. Tissue sections from areas adjacent to those sites sampled for digestion were found to be without ferruginous bodies (FB) or histopathology consistent with asbestos-induced changes. All individuals had 20 or less FBs per gram of digested wet lung, a number considered to reflect general population levels. Tissue analysis of uncoated fiber burden was carried out by analytical electron microscopy. There was a trend of a higher likelihood of FB and asbestos fiber content correlated with age. RESULTS: The data are not consistent with the findings that chrysotile is readily found in lung tissue from the general population, in that none was found in 19 of the cases. It was almost as likely that one would find anthophyllite (12 of 33 cases) in this study. The commercial amphiboles (amosite and crocidolite) were occasionally found in the tissue from the general population and, when observed, were few in numbers. Twenty-six of the patients had no FBs and ten had no uncoated asbestos fibers within the limits of detectability in this study. CONCLUSIONS: The total tissue burden of asbestos in this study is much less than earlier reported observations from other general populations. PMID- 9987562 TI - Mortality study in an Italian oil refinery: extension of the follow-up. AB - This article present the results of the extension of the follow-up of a cohort of workers employed in an Italian oil refinery. 1,583 workers employed in 1949-1982 in a northern Italy oil refinery plant were followed-up for mortality as of May 31, 1991. Environmental measurements documented potential exposure to benzene. Standardized mortality ratios (SMR) and their 95% confidence intervals (95% CI) were calculated using as references national (1949-1968) and regional mortality rates (1969-1991). Elevated mortality from lymphoma (seven deaths, SMR 190, 95% CI 76-391) and leukemia (eight deaths, SMR 225, 95% CI 97-443) was observed. No consistent trends by length of employment or time since first exposure were apparent. Nonetheless, the excess risk was particularly and significantly increased among workers with 15 or more years of employment, and 30 or more years since first employment. The findings of elevated mortality from leukemia and lymphoma are in agreement with those of other oil refinery studies. Chance, confounding, or other biases might have played a marginal, if any, role in determining the results. Exposure to benzene is a biologically plausible explanation. PMID- 9987563 TI - Injuries in home health care workers: an analysis of occupational morbidity from a state compensation database. AB - BACKGROUND: Home health services represent one of the fastest-growing segments of the US economy. Home health care workers (HHCWs) might be expected to have a high incidence and increased severity of injury because of inherent difficulty in control over their work environment, and the limited amount of research on injuries in home health care appears to support this hypothesis. METHODS: Using data on workers' compensation claims for 1995-1996 from a large state database, we calculated the incidence, frequency, and types of injuries occurring in this working population. Comparison data were drawn from nursing home (NH) and hospital-based nursing personnel. RESULTS: An incidence of 52 injuries per 1,000 workers per year was calculated; this rate lies between nursing home workers (132/1,000) and hospital-based workers (46/1,000). The percentage of indemnified (> 3 days lost-time) injuries was increased over those occurring in nursing home personnel. Mean number of days lost from work by home health workers was 44, significantly increased from the average 18 and 14 days lost by NH and hospital nursing workers, respectively. Mean indemnity payment was $1,523 and mean medical costs were $1,276 per injury. Permanent partial disability awards were made to 19 (4.9%) of the injured HHCWs during the 2-year study period; back injuries accounted for 63% (12) of these awards. Overexertion injuries and falls accounted for 63% of total injuries in this group of workers, while 13.5% occurred as a result of motor vehicle accidents. The incidence of injury attributed to motor vehicles in HHCWs was 7 per 1,000 workers per year, an order of magnitude greater than in NH and hospital workers. CONCLUSIONS: These data indicate that injuries to HHCWs, though less frequent than in their nursing home counterparts, result in greater lost time from work and accompanying costs, which may indicate greater severity of injury. Characteristics of home health work, including increased intensity and speed of work, adverse working conditions, and the necessity of motor vehicle transportation as a condition of work may be contributors to injury in this setting. Further investigation of determinants of accidents and injuries in home health care, both in the actual setting where the work takes place and in the way it is structured, is warranted. PMID- 9987564 TI - Fatal occupational injuries among electric power company workers. AB - Surveillance data suggest high rates of electrocutions and fatal falls among workers in electric utility companies, who may be exposed to electric current, heights, flammable agents, and frequent motor vehicle travel. To characterize the occurrence of fatal injuries among electric utility workers, we studied workers in five electric power companies in the United States. A cohort of 127,129 men hired between 1950 and 1986 was followed through 1988. Injuries at work were identified through manual review of death certificates. The occurrence of occupational injuries was analyzed with directly adjusted rates and Poisson regression. The overall rate of fatal occupational injuries was 13.20 per 100,000 person-years (n = 192), with 76% due to electric current, homicide, and falls from heights. Deaths were concentrated in a few groups with elevated injury rates, notably linemen (rate ratio (RR) 3.33), electricians (RR 2.79), and painters (RR 3.27). Occupations requiring daily work on elevations or frequent, direct contact with energized electrical equipment experienced markedly higher rates of fatal injury from falls and electrocutions with rate ratios of 21.8 (95% confidence interval (CI) 11.4-41.5) and 16.7 (95% CI 6.6-42.6), respectively, independent of worker age and seniority. Although fatal injury rates in this industry have declined in recent decades, significant numbers of deaths still occur. Based on the premise that all injuries are preventable, a need for continued vigilance and efforts at prevention is indicated. PMID- 9987565 TI - Back pain and agricultural work among farmers: an analysis of the Colorado Farm Family Health and Hazard Surveillance Survey. AB - BACKGROUND: Back pain is the most prevalent occupational health problem experienced by much of the world's workforce. However, agricultural work-related back pain occurring among US farmers working on small operations or family farms is usually not included in surveillance. With data collected by Colorado Farm Family Health and Hazard Surveillance Survey, this study reports characteristics of and risk factors for back pain among adult farmers living in eight Colorado counties. METHODS: A stratified probability sample of 500 farms was selected in proportion to the number of farms in study areas. During the 4-year period from 1993 through 1996, 458 farms were enrolled in the study and 759 farmers were interviewed using a questionnaire. Information on self-reported back pain and potential risk factors among 742 white farmers was evaluated and reported here. RESULTS: A total of 194 farmers (26.2%) reported to have had at least one episode of back pain lasting for 1 week or more. Males had a slightly higher prevalence of back pain than females (28.6% vs. 22.5%) and the lower back was the predominantly affected part of body among both males and females. In 45.4% of males and 43.9% of females back pain was brought on by repeated activities. Males' activities at work were more likely to cause back pain while females' activities at home were more likely to cause back pain. Three factors were found to be significantly associated with back pain: being depressed (odds ratio (OR) = 3.68, 95% confidence interval (CI) = 2.23-6.09), farming/ranching as main activities (OR = 1.66, CI = 1.17-2.36), and worked in agriculture for 10 to 29 years (OR = 1.62, CI = 1.14-2.30). CONCLUSIONS: Our analyses indicate that back pain is an occupational health problem among farmers on small operations or family farms and that back pain affected males and females differently. The finding of significant positive associations between depression, farming activities, and back pain warrants further attention. PMID- 9987566 TI - Methicillin resistant Staphylococcus aureus as a cause of chorioamnionitis. AB - BACKGROUND: Chorioamnionitis is a leading cause of morbidity and mortality in preterm infants. Only rarely is Staphylococcus aureus implicated. A case of methicillin resistant Staphylococcus aureus causing chorioamnionitis and endometritis is presented. CASE REPORT: A 39-year-old gravida 2 para 1 female, who previously worked as the unit clerk in the pediatric pulmonary unit of a children's hospital, was initially admitted at 22 weeks with a shortened cervix. The patient refused emergency cerclage. She was released from the hospital and returned at 25 4/7 weeks' estimated gestational age with possible spontaneous rupture of membranes. An amniocentesis was performed and revealed a gram stain positive for many gram positive cocci as well as a glucose of < 2 mg%. The patient was started on intravenous ampicillin and gentamicin and induction of labor with oxytocin was begun. Approximately 1 day after the patient's delivery, the culture from the amniocentesis was noted to have grown methicillin resistant Staphylococcus aureus, and the patient's (as well as the neonate's) regimen was switched to vancomycin. CONCLUSION: A Medline search revealed no cases of methicillin resistant Staphylococcus aureus causing chorioamnionitis. When chorioamnionitis or refractory endometritis is encountered in a patient who works in the health care industry, methicillin resistant staphylococcus aureus must be considered. PMID- 9987567 TI - The influence of tamoxifen on the maturation index of vaginal epithelium. AB - PURPOSE: The estrogenic effect of tamoxifen on vaginal epithelium in postmenopausal women with breast cancer was evaluated over a period of more than 48 months. METHODS: The tamoxifen group consisted of 118 postmenopausal patients, control group I of 30 postmenopausal women with breast cancer receiving no tamoxifen or hormonal replacement therapy and control group II of 40 postmenopausal women without breast cancer taking no hormones. We determined the maturation index of the vaginal epithelium. Pearson's chi-square-test and t-test for independent samples were used in the statistical analysis. RESULTS: The maturation index increased under tamoxifen therapy within the first 24 months from 0.4026 before taking tamoxifen (n = 64) to 0.6066 (n = 162, p < 0.0001) and in the following 24 months to 0.6325 (n = 122, p < 0.0001). Under tamoxifen intake of more than 48 months, an additional small increase of the maturation index to 0.6735 (n = 42, p < 0.0001) could be noticed. The maturation index in the tamoxifen group was statistically significantly higher (p < 0.0001) than in the control groups (control group I: 0.3975, p < 0.0001; control group II: 0.4102, p < 0.0001). CONCLUSION: An apparent increase in the maturation of the vaginal epithelium caused by the estrogenic effect of tamoxifen could be demonstrated. PMID- 9987568 TI - Suppressed apoptotic susceptibility in human endometrial epithelial cells pretreated with hepatocyte growth factor. AB - Hepatocyte growth factor (HGF) and its receptor are strongly expressed perimenstrually in human endometrial epithelium, but their functions remain unknown. In this study the effects of HGF on Fas-mediated apoptosis in the human endometrial epithelial cell line HHUA were investigated. It was found that HGF inhibited Fas-mediated growth suppression and DNA fragmentation in the cells without any increase in Fas antigen expression on the cells. This results suggests that HGF inhibits Fas-mediated apoptotic signals in the endometrium, and possibly plays a role in reshaping the endometrium during menstruation. PMID- 9987569 TI - Essential mixed type II cryoglobulinemia in a HCV positive pregnant woman: case report. AB - Cryoglobulins are a group of proteins with the common property of precipitating from cooled serum. Cooled cryoglobulinemia is a classic disease caused by immune complexes which subside on vessel walls and produce a clinical picture represented by recurrent purpura, asthenia, arthralgias, Raynaud's phenomenon, glomerulonephritis and sensorimotor neuropathy. The authors describe a case of a patient C.M., 37 years old, with cryoglobulinemia, chronic hepatitis C and gravidic cholestasis at 28 weeks' gestation. The clinical picture worsened with the appearance of mild hypertension with proteinuria and hypochromic anaemia. At 31 weeks' the arthralgic symptomatology and pruritus revealed degeneration with an alteration of glycemic profile values and treatment with rapid human insuline was started. The cardiotocography began to be pathologic and a cesarean section was performed; the newborn weighted 1570 g. Cooled cryoglobulinemia is a pathology which worsens in a gravidic state and can impair the outcome of pregnancy. PMID- 9987570 TI - Ultrasonographic evaluation of hysterectomized patients with and without concomitant adnexectomy? AB - OBJECTIVE: To present our experience with the use of ultrasonography in the evaluation of hysterectomized patients. METHODS: The study group was comprised of 100 consecutive women referred to our ambulatory unit for pelvic sonographic evaluation between April 1, 1996 and March 31, 1997. Inclusion criteria were previous hysterectomy for a benign condition with or without concomitant bilateral salpingo-oophorectomy and available medical and gynecological histories. RESULTS: No significant difference was observed in the rate of abnormal ultrasonographic findings among the patients who had had bilateral salpingo-oophorectomy 5/50 and those who had not (8/50). There was also no significant difference in pelvic mass rate between the patients who were receiving hormone replacement therapy and those who were not. The sensitivity of sonography in our study was 100% and the positive predictive value, 84.5%. CONCLUSIONS: Sonography is a useful diagnostic tool in the follow-up and management of post-hysterectomy patients. PMID- 9987571 TI - Biochemical markers of n-3 long chain polyunsaturated fatty acid intake during pregnancy. AB - BACKGROUND: To assess the relationship between the mothers' intake of n-3 long chain polyunsaturated fatty acids (LC PUFA) during pregnancy and their levels in plasma and tissue. METHODS: 162 mothers were studied during labor. Three groups were differentiated according to the n3 LC PUFA intake assessed by means of a dietetic interview: superior intake (SIG) (> 0.721 g/day), medium intake (MIG) (from 0.382 to 0.721 g/day) and inferior intake (IIG) (< 0.381 g/day). Fatty acids (FA) were studied by capillary chromatography in plasma and in erythrocyte phospholipids. RESULTS: The fatty acids (FA), expressed in absolute values, did not show any significant differences among the aforementioned groups. However, three were some trends which were confirmed when the FA were expressed in percentages. Thus, higher levels of docosahexaenoic acid (DHA) were found in SIG both in plasma and in the erythrocyte membrane, when expressed in percentages. Eicosapentaenoic acid (EPA) was also higher in the SIG in the erythrocyte membrane, whereas in plasma the differences were of marginal significance. On the other hand, arachidonic and linoleic acids had lower values in the SIG in erythrocytes. The theoretical optimal intake of n-3 LC PUFA corresponded to a plasma concentration of 117.9 +/- 45.9 mcg/ml n-3 LC PUFA or 2.54% of the total fatty content (2.29% of DHA). The corresponding cut-offs in erythrocyte membranes were 7.54% of total lipids (5.59% of DHA). CONCLUSION: The best markers of n-3 LC PUFA intake were DHA for plasma and DHA and EPA for erythrocyte phospholipids, all of them expressed in proportions of total FA. The arachidonic and linoleic acids (in percentages) in erythrocyte phospholipids were also good markers of n-3 intake. This probably reflects the metabolic competition between both PUFA families. PMID- 9987572 TI - Intrapartum vibratory acoustic stimulation after maternal meperidine administration. AB - OBJECTIVE: To examine the effectiveness of the acoustic stimulation test in the interpretation of suspicious cardiotocograms obtained after meperidine administration to the mother during the first stage of labor. SUBJECTS AND METHODS: We studied 45 unselected parturients who received 50 mg meperidine i.m. when cervical dilatation was 5 cm. In all cases a decreased beat-to-beat variability of the fetal heart rate and fetal movements was noted after the injection of meperidine. A vibratory acoustic stimulation was performed in 25 patients (group A) while the remaining 20 (group B) had no stimulation. RESULTS: After the meperidine injection, the acoustic-induced reactivity returned immediately in group A, while the spontaneous reactivity returned 30 minutes later. The mean number of fetal movements in all parturients was 8.71 +/- 2.18 before meperidine administration. Sixty minutes after the meperidine injection the mean number was 8.52 +/- 2.48 in group A and 1.65 +/- 1.81 in group B (p < 0.0001). CONCLUSION: The acoustic stimulation test is an effective method of interpreting suspicions CTG's obtained after meperidine administration to the mother during the first stage of labour. PMID- 9987573 TI - Aggressive angiomyxoma of the vulva: expression of estroprogestinic receptors and follow-up. AB - PURPOSE OF INVESTIGATION: To analyze aggressive angiomyxoma hormone-dependency. METHOD: Estroprogestinic receptor expression was studied by immunohistochemistry in 5 patients with aggressive angiomyxoma of the vulva. RESULTS: The immunohistochemical results confirm the positivity of angiomyxoma for estrogen and progesterone receptors. CONCLUSIONS: We hypothesized that the concomitant factor favoring neoplastic growth is a different genetic substrate specific in the female sex. Analysis of the data regarding the distribution of angiomyxomas in different age groups has strengthened this hypothesis suggesting that this tumor is correlated with complete maturity, in all probability hormonal. However it cannot be excluded that the tumor begins to develop at an early age, but since it has a slow growth rate, the phenomenon is delayed and is related to hormonal stimulation. PMID- 9987574 TI - Intrauterine insemination IUI: the effect of ovarian stimulation and infertility diagnosis on pregnancy outcome. AB - We determined the intrauterine insemination (IUI) pregnancy outcome in the same group of patients when applying different methods of ovulation induction. A group of patients with unexplained (no. 46) and male factor infertility (no. 101) consented to have the following treatment protocol at the American University of Beirut-Infertility Center: IUI to be performed in three natural ovulatory cycles in all patients, then in three clomiphene citrate (CC) stimulated cycles in the remaining non-pregnant patients, and then three cycles with controlled ovarian hyperstimulation (COH) in the remaining group. Of the total 147 patients 130, 138 and 123 underwent 273 natural, 278 CC and 266 COH IUI cycles, respectively. Semen processing for IUI was done by washing the sperm twice and using the swim-up technique. The chi-square test was used for statistical analysis. Pregnancy rate per cycle of IUI with COH (9.8%) was significantly higher than that of IUI in natural cycles (3.3%) but approached significance when compared to IUI with CC cycles (5.4%). Also unexplained infertility cases had a significantly higher pregnancy rate (58.7%) when compared to that of male factor cases (22.8%). IUI still has a place in the treatment of infertility due to selective causes. Combined with COH, IUI gives the best pregnancy rate although its benefit with natural or CC cycles remains obvious. PMID- 9987575 TI - Severe coital injury after Frank's creation of a neovagina. AB - A neovagina was created by the Frank's dilatation method in a girl with vaginal agenesis. At the first coital attempt complete laceration of the cul de sac with copious bleeding occurred. Daily application of estrogen cream was the only therapy until complete healing after four weeks. Possible causes and therapeutic approaches are discussed. PMID- 9987576 TI - Prenatal diagnosis of thanatophoric dwarfism in second trimester. A case report. AB - Thanatophoric dwarfism is a lethal, rare osteochondrodysplasia and results from mutations on the fibroblast growth factor receptor 3 (FBGFR3) gene, on the short arm of chromosome 4. In this paper, we present a case of thanatophoric dwarfism diagnosed in the 18th pregnancy week. PMID- 9987577 TI - Unusual localisation of an ectopic pregnancy. AB - We present a case of ectopic pregnancy with a peculiar localisation: beneath the peritoneal serosa covering the anterior wall of the uterus, at the level of the uterovesical pouch. The case raised some diagnostic and management problems for the medical team. Considerations are made concerning the etiopathology of this unusual form of ectopic pregnancy. PMID- 9987578 TI - Clomiphene citrate challenge test: cycle to cycle variability of cycle day 10 follicle stimulating hormone level. AB - The clomiphene citrate challenge test (CCCT), a means of assessing ovarian reserve, was shown by several studies to have an excellent predictive value for achieving conception in natural cycles, during ovulation induction and in-vitro fertilization cycles. Accordingly we elected to study the cycle to cycle variability of CCCT so as to determine the reliability of a single CCCT result. Two groups of patients were studied, the first (n = 40) were those patients who were performing the test because it was indicated, and the second (n = 24) were those who were receiving clomiphene citrate for ovulation induction. In both groups CCCT intercycle variability was significant in 75% of the cases, but this variability altered the prognostic values of the test in only 40% of the first group. In conclusion, our study showed a high percentage of intercycle variability of CCCT but further studies are needed to evaluate the influence of this variability on potential conception. PMID- 9987579 TI - Campomelic dysplasia in a twin pregnancy. A case report. PMID- 9987580 TI - Effect of combined iron therapy (Chemiron) and single iron therapy on the dexamethasone-estriol test effect, on plasma dehydroepiandrosterone sulfate during normal pregnancy. AB - It is established that during human pregnancy maternal and fetal serum dehydroepiandrosterone sulfate (DHAS), which has been shown to arise mainly by adrenal secretion, serves as a substrate in the biosynthesis of placental oestrogen. The conversion to oestrogen is reflected by decreased DHAS and increased oestrogen concentration in the peripheral maternal blood. Impaired uteroplacental perfusion has been shown to play a role in the pathogenesis of some complicated pregnancies with placenta insufficiency. Apart from this, lower oestrogen, magnesium and zinc levels are found in many of these conditions in the third trimester with placenta insufficiency. In this study, we examined the effect of 4 mg Dexamethasone intravenously on dehydroepiandrosterone sulfate, since materal cortisol or synthetic corticosteroids cross the placental barrier and inhibit the release of dehydroepiandrosterone sulfate in fetal adrenals. Dexamethasone was found to suppress dehydroepiandrosterone sulfate levels in all groups but a significant difference in suppression was found between the Chemiron -a hematinic combination--and the single iron therapy control groups. Our preliminary results showed that Chemiron has a protective effect on the development of placenta insufficiency during the third trimester of pregnancy. PMID- 9987581 TI - Eating behavior of bulimics, self-identified binge eaters, and non-eating disordered individuals: what differentiates these populations? AB - This article reviews and critiques the eating behavior literature comparing the binge and non-binge-eating episodes of three populations of normal-weight women: bulimics, self-identified binge eaters, and non-eating-disordered women. The specific behaviors evaluated are number of calories consumed during different types of eating episodes, frequency of binge eating, number of eating episodes, rate of food consumption, the macronutrient composition of the food ingested, and context and duration of eating. Differences in these populations' eating behavior are analyzed in terms of their theoretical contribution. It is concluded that differences in the observed behavior of these groups are consistent with restraint theory, purge opportunity, and the forbidden foods hypothesis. Conversely, results do not support carbohydrate craving theory or a deficit in the satiety mechanisms of bulimics. Suggestions for future research are presented. PMID- 9987582 TI - The role of dieting in binge eating disorder: etiology and treatment implications. AB - Dieting has been implicated as a potential contributor in the development of binge eating problems in binge eating disorder (BED). If dieting plays a causal role in the etiology of BED, this could have major implications for understanding and treating individuals with the disorder. This article reviews the existing literature on the role of dieting in BED. Retrospective studies of dieting history, research on levels of dietary restraint, and prospective studies investigating the effects of dieting on subsequent eating behavior are explored. Although the literature is inconclusive as to the exact role that dieting plays in the etiology of BED, recommendations for future research and suggestions for treatment are given. PMID- 9987583 TI - Culturally competent research: an ethical perspective. AB - This article addresses the perspective of the Ethical Principles and Guidelines for Providers regarding issues affecting research with ethnic minority populations. Issues such as failure to report or give informed consent to research participants, lack of diversity among researchers, inappropriate study of ethnic minority populations, and culturally insensitive assessment instruments are discussed. Examples of recommended responsibilities and criteria for culturally competent research are provided, including increased involvement of minorities in research, both as investigators and concerned citizens. In sum, the recommendations address the larger problem of failure to acknowledge people in their cultural context. Finally, implications for the Ethical Principles and Guidelines for Providers are considered. PMID- 9987584 TI - A review of cognitive factors in the etiology of rape: theories, empirical studies, and implications. AB - In the past decade, research into the etiology of rape has increasingly focused on cognitive variables. The studies reviewed in the present article provide evidence that men with a high proclivity to rape have more rape supportive attitudes, are more likely to consider victims to be responsible for rape, and are less knowledgeable about the negative impact of rape on the victims. These men tend to misperceive cues emitted by women in heterosocial interactions; fail to generate inhibitory self-verbalizations to suppress association of sex and aggression; and have more coercive, sexual fantasies. Furthermore, a high proclivity to rape is associated with a semantic network in which concepts of sex and power are closely linked in such a way that power cues are necessary precursors of sexual feelings. Multivariate studies suggest that rape-supportive attitudes interact with noncognitive factors in the etiology of rape. Implications for rape prevention and treatment of rapists are considered. Finally, methodological issues are discussed, and recommendations for future research are given. PMID- 9987586 TI - Beyond pain: the role of fear and avoidance in chronicity. AB - The purpose of the present article is to provide unification to a number of somewhat disparate themes in the chronic pain and phobia literature. First, we present a summary review of the early writings and current theoretical perspectives regarding the role of avoidance in the maintenance of chronic pain. Second, we present an integrative review of recent empirical investigations of fear and avoidance in patients with chronic musculoskeletal pain, relating the findings to existing cognitive-behavioral theoretical positions. We also discuss several new and emerging lines of investigation, specifically related to information processing and anxiety sensitivity, which appear to be closely linked to pain-related avoidance behavior. Finally, we discuss the implications of the recent empirical findings for the assessment and treatment of individuals who experience disabling chronic musculoskeletal pain and suggest possible avenues for future investigation. PMID- 9987585 TI - Empirical foundations for writing in prevention and psychotherapy: mental and physical health outcomes. AB - The use of writing, alone or in conjunction with traditional psychotherapy, has increased substantially in recent years. The most widespread use of writing has been for single-shot ad hoc purposes or to log behavior. The purpose of this review is to summarize a decade of research demonstrating the efficacy of writing about past traumatic experiences on mental and physical health outcomes. It is widely acknowledged in our culture that putting upsetting experiences into words can be healthy. Research from several domains indicates that talking with friends, confiding to a therapist, praying, and even writing about one's thoughts and feelings can be physically and mentally beneficial. This review highlights advances in written disclosure that determine some therapeutic outcomes. In addition, we attempt to explore the mechanisms that predict improved psychological and physical health. Finally, limitations of previous studies are highlighted, and suggestions for future research and application are made. PMID- 9987587 TI - Update on vertigo management. AB - Over the past decade, the treatment of vertigo has shifted from medical and surgical modalities in favor of physical therapy. When more aggressive treatment is necessary, patients may be treated with less invasive surgical modalities. This article provides an overview of recent advances. PMID- 9987588 TI - Venous thrombosis: diagnosis and treatment; new methods and strategies for management. AB - Venous thrombosis most often attacks patients who have had alterations of venous stasis, endothelial damage, and/or hypercoagulability. Diagnosis generally depends on venography or duplex doppler ultrasonography; treatment is usually started with heparin and may proceed to warfarin alone. PMID- 9987589 TI - Antimicrobial resistance in community-acquired respiratory tract pathogens. AB - Antimicrobial resistance among common respiratory pathogens has become a significant problem. However, there remain multiple treatment options, including the newer macrolides, third-generation cephalosporins, beta-lactam/beta-lactamase inhibitor antibiotics, and the newer fluoroquinolones. PMID- 9987590 TI - Gastroduodenal ulcers: causes, diagnosis, prevention and treatment. AB - During the past decade, new acid antisecretory drugs have been developed, and our understanding of the mechanisms of mucosal ulceration has been broadened. However, the major change has been an appreciation of the role of Helicobacter pylori in peptic ulcer disease. PMID- 9987591 TI - Concussion in sport: diagnosis, management, return to competition. AB - Concussions can occur in any sports activity. Although no standards for grading and managing concussions exist, many sets of guidelines have been proposed. Therefore, physicians should be familiar with at least one set to assist in diagnosing and managing concussions. PMID- 9987592 TI - Clinical practice guidelines: questions family physicians should ask themselves. AB - Family physicians increasingly are being pressured to use clinical practice guidelines. This article reviews the methods of developing, disseminating and implementing guidelines, and suggests a list of questions that family physicians should ask themselves before accepting any clinical practice guidelines. PMID- 9987593 TI - ACR presentations support Salagen tablets as a safe and effective treatment for the dry mouth symptoms caused by Sjogren's syndrome. PMID- 9987594 TI - Parke-Davis announces market availability of Omnicef--a new, broad-spectrum cephalosporin antibiotic. PMID- 9987595 TI - Duke study searches for most effective ways to get smokers to kick their habit. PMID- 9987596 TI - BPH survey reveals confusion about condition that strikes 80% of men by age 80. PMID- 9987597 TI - Abbott introduces new test for cardiac diagnostic: first automated test to measure levels of homocysteine in blood. PMID- 9987598 TI - Low-fat diet alone reversed type 2 diabetes in mice. PMID- 9987599 TI - Recent advances in chemokines and chemokine receptors. AB - Chemokines are a superfamily of small cytokine-like molecules which have been described primarily on the basis of their ability to mediate the migration of verious cell types, particularly those of lymphoid origin. The receptors for these molecules are all seven-transmembrane domain G protein-coupled receptors that have historically been excellent targets for small-molecule drugs. This fact, coupled with the advent of large-scale DNA database mining and the recognition that chemokine receptors are also coreceptors for HIV, has driven discovery in this field at a tremendous rate. This process has included not just an expansion of the number of known chemokines and chemokine receptors, but also a greater appreciation for the variety of functions that chemokines are involved in. We review here the molecules that have come from the most recent years of chemokine research as well as many of the new functions that have been ascribed to them. PMID- 9987600 TI - Mechanisms of lipid antigen presentation by CD1. AB - CD1 is a family of cell surface glycoproteins that are related in structure and evolutionary origin to the major histocompatibility complex (MHC)-encoded antigen presenting molecules. In contrast to MHC-encoded antigen-presenting molecules, CD1 binds and presents lipid and glycolipid antigens for specific recognition by T cell antigen receptors. Recent work shows that several CD1 family members colocalize with MHC class II proteins within the endocytic system of antigen presenting cells. Detailed studies of the intracellular trafficking of CD1 proteins reveal new mechanisms controlling delivery of antigen-presenting molecules to particular compartments within cells. The combination of overlapping yet distinct trafficking routes for the various CD1 family members, combined with emerging information on the heterogeneity of CD1-presented lipid antigens, suggest a model whereby different members of the CD1 family could present antigens that occur in various cellular compartments. Furthermore, the CD1 family as a group may present antigens from pathogens that are not normally accessible to or efficiently surveyed by the MHC Class I or II systems. The discovery of this third pathway for antigen presentation, together with the appreciation of a previously unrecognized universe of nonpeptide lipid antigens for T cell responses, are likely to have broad implications for our understanding of the cell-mediated immune response and its role in health and disease. PMID- 9987602 TI - The human side of medicine: how can we teach it? PMID- 9987601 TI - Therapeutic effects of substances occurring in higher Basidiomycetes mushrooms: a modern perspective. AB - This review highlights some of the recently isolated and identified substances of higher Basidiomycetes mushrooms origin that express promising antitumor, immune modulating, cardiovascular and hypercholesterolemia, antiviral, antibacterial, and antiparasitic effects. Medicinal mushrooms have a long history of use in folk medicine. In particular, mushrooms useful against cancers of the stomach, esophagus, lungs, etc. are known in China, Russia, Japan, Korea, as well as the U.S.A. and Canada. There are about 200 species of mushrooms that have been found to markedly inhibit the growth of different kinds of tumors. Searching for new antitumor and other medicinal substances from mushrooms and to study the medicinal value of these mushrooms have become a matter of great significance. However, most of the mushroom origin antitumor substances have not been clearly defined. Several antitumor polysaccharides such as hetero-beta-glucans and their protein complexes (e.g., xyloglucans and acidic beta-glucan-containing uronic acid), as well as dietary fibers, lectins, and terpenoids have been isolated from medicinal mushrooms. In Japan, Russia, China, and the U.S.A. several different polysaccharide antitumor agents have been developed from the fruiting body, mycelia, and culture medium of various medicinal mushrooms (Lentinus edodes, Ganoderma lucidum, Schizophyllum commune, Trametes versicolor, Inonotus obliquus, and Flammulina velutipes). Both cellular components and secondary metabolites of a large number of mushrooms have been shown to effect the immune system of the host and therefore could be used to treat a variety of disease states. PMID- 9987603 TI - Building a regional clinical campus: experience with preclinical students. PMID- 9987604 TI - Resident resistance. AB - Clearly, faculty must work hard with residents to explore the nature of their resistance to a program's learning and growth opportunities. Initial steps to a deeper, more effective, and longer-lasting change process must be pursued. If resident resistance is mishandled or misunderstood, then learning and professional growth may be sidetracked and the purposes of residency training defeated. Listening to the whole person of the resident and avoiding the trap of getting caught up in merely responding to select resident behaviors that irritate us is critical. Every faculty member in the family practice residency program must recognize resistance as a form of defense that cannot immediately be torn down or taken away. Resident defenses have important purposes to play in stress reduction even if they are not always healthy. Residents, especially interns, use resistance to avoid a deeper and more truthful look at themselves as physicians. A family practice residency program that sees whole persons in their residents and that respects resident defenses will effectively manage the stress and disharmony inherent to the resistant resident. PMID- 9987605 TI - Perspectives on longer community-based preceptorships. PMID- 9987606 TI - Through the looking glass. PMID- 9987607 TI - Clinical and cultural issues in caring for deaf people. AB - BACKGROUND AND OBJECTIVES: The clinical practice of family medicine is increasingly cross-cultural. Promoting culturally sensitive and competent health care is one of the goals of medical educators in guiding medical students and residents, as well as designing continuing education for family physicians. Working with minority communities is essential to meet that goal. The Deaf community is a linguistic and cultural minority group that is often overlooked. Working with the Deaf community to help develop cultural competency and sensitivity has potential benefits. This article introduces some of the sociocultural experiences of deafness and their relevance in health care settings. PMID- 9987608 TI - Retention of family medicine faculty development fellows in academic medicine. AB - OBJECTIVE: This study measured the retention of family medicine faculty development fellows in academic medicine. METHODS: Surveys were sent, in two stages, to 1) fellowship program directors and 2) fellows. These surveys were about full-time faculty development fellowships with new or continued Title VII funding during the interval of 1993-1996. Retention as faculty was the primary outcome. Likelihood of leaving academics and service in a federally designated medically underserved area were secondary outcomes. RESULTS: The fellowship program directors survey produced an 88% response rate and identified 105 alumni. The survey of fellows yielded a response rate of 73% (n = 77). The retention rate of these newly graduated family medicine fellows in academic positions was 75% (n = 58). A total of 37% (n = 21) of alumni in full- and part-time teaching positions reported being likely to leave their current position within the next 2 years. CONCLUSIONS: Retention rates of newly graduated family medicine fellows in academic positions are similar to rates reported in the 1980s. This group anticipates a high job turnover within the next 2 years. PMID- 9987609 TI - Variability in the learning experiences of family practice residents during an obstetrics rotation. AB - BACKGROUND AND OBJECTIVES: Residency rotations do not necessarily provide the same clinical experience to each resident. This study quantified and explained the variability in participation in deliveries by family practice residents during an obstetrics rotation at a community hospital. METHODS: We collected prospectively completed resident experience logs from 17 residents and information from the hospital Summary of Delivery forms for 1,166 deliveries. The data were analyzed using methods to account for within-supervisor correlation. RESULTS: Participation and delivery rates varied markedly. In stepwise conditional regression analysis, resident participation in deliveries was positively associated with prior resident involvement during the labor and negatively associated with occurrence of the delivery on the night shift and with male gender of the resident. Resident performance of delivery was positively associated with non-instrumented vaginal delivery, prior resident involvement during the labor, and patient multiparity and negatively associated with male resident gender. CONCLUSIONS: We found substantial variability in resident experience and identified several factors associated with increased resident experience. Variability of experience among residents in clinical rotations should be assessed to ensure that all residents receive adequate training. PMID- 9987610 TI - The role of the chair's spouse in academic departments of family medicine. AB - BACKGROUND AND OBJECTIVES: Family medicine has the highest percentage of unfilled budgeted faculty positions of all clinical and basic science departments. To successfully recruit and retain academic leaders, personal and professional issues need to be recognized and valued. This study reports the results of a national survey of chairs and an important, often overlooked factor in recruitment and retention--the spouse of the department chair. METHODS: Questionnaires were sent to 107 chairs of academic departments or divisions of family medicine and their spouses. RESULTS: There was a usable response rate of 86%, and data from 85 questionnaires (79%) were analyzed. The spouses' highest role priority was family, perhaps reflecting their relatively young mean age of 48.6 years. There was a statistically significant correlation between those who were "oriented" to the role of chair's spouse and a higher level of participation in departmental activities. Data are also reported on spouse role satisfaction, expectations, and factors in deciding to stay or leave their current location. CONCLUSIONS: The results suggest that with the increased competition for family physicians in a multitude of practice settings, search committees for family medicine department chairs need to be innovative and attentive to personal as well as professional factors in recruiting and retaining future and current department chairs. It would be prudent to acknowledge the role of the spouse in decisions concerning job selection and satisfaction. PMID- 9987611 TI - That family practice feeling. PMID- 9987612 TI - [Occupational medicine and quality]. AB - The discipline of occupational medicine has always maintained a closed relationship with the quality system, starting from the well known quality assurance practices, up to the quality of health services, and the concept of prevention and health promotion as essential components of quality programs. The quality of health care has emerged as an area of high interest and concern, driven by the consideration of public policy and the desire of health care government to maximize the value of their investments. However, when we move to apply quality principles to health service some difficulties emerge. For example the introduction of DRFs system makes uneconomical the diagnosis in occupational medicine, since the costs are determined by the type and the number of hazards to be identified and assessed and not only by the risk factors of by the worker's pathology. Moreover, resources are necessary for the correct evaluation of non occupational pathologies often present, both for deontological and legal reasons. The attention to the role of occupational medicine in quality programs has been increased by the recognition of the adverse impact of preventable or controllable risk factors in health benefit and disability costs and employee productivity. By this way prevention and health promotion will become an essential part of quality procedures able to guarantee and maintain quality objectives. PMID- 9987613 TI - [SV40 as a possible cofactor in the etiopathogenesis of mesothelioma and other human tumors]. AB - Simian virus 40 (SV40) has been introduced into the human population with contaminated polio vaccines between 1955 and 1963. Previous research conducted by southern blot hybridization and recent analysis by PCR have shown the presence of SW0 sequences in human brain tumors, mesotheliomas and osteosarcomas as well as in normal tissues such as blood and sperm fluids. SV40 RNA and T antigen were detected in the same tissues. All the samples were coinfected by BK Virus (BKV), suggesting that BKV may have a helper function for SV40 replication in human cells. The presence of SV40 in human tumors suggests that the virus may be a cofactor in the etiopathogenesis of human neoplasia. In addition, blood and semen may represent the vectors for transmission of SV40 by horizontal infection in the human population. PMID- 9987614 TI - [Aromatic polycyclic hydrocarbons: chemism, vehicles and technics for protection from toxicological risk]. AB - In this work we take under examination the aromatic polycyclic hydrocarbons (APHs) as a class of organic micropolluting agents which have a considerable impact in the life and in the working environment of man. The authors decided to expressly start this study by proposing the changes pattern cause by APHs according to their chemical-physical reactivity characteristics, in order to realise a qualitative and quantitative evaluation of their toxicologic impact. Therefore, the specific aspects of chemism (reactions of substitution, aromatic electrophilia and addition) of these organic micropolluting agents are studied with particular reference to their chemical structure and to the properties which are the main important cause of every effect of diffusion both in productive environments and of toxicity in the human body. In this way, come toxicologic risk sources, responsible, within some technological cycles for the APHs emission in the working areas, are identified, shown and evaluated; carrying factors, not much investigated till now, which represent a synergic effect to the introduction and absorption of the APHs by the human body. For the necessity of a useful environmental monitoring which could be applied to different matrices, the techniques and the methods useful for carrying out sampling and analytical evaluation in a correct way, are introduced as well. Lastly, the Authors stress on the engagement and discuss the measures of prevention and protection, technically performable on the basis of the chemico-physical-granulometric properties of APHs, with the goal of safeguarding at best health of people occupationally exposed. PMID- 9987615 TI - [The energy cost and the use of individual protective devices in firefighters]. AB - Firefighters are required to wear fire-protection devices when involved in hazardous work situations. To determine whether fire protective clothing and self contained breathing apparatus (SCBA) affect maximal physical work performance and to assess their additional energy requirement, we studied a cohort of Italian firemen while performing a rapid air-stair climbing (Mt. 29). Heart rate (HR) and maximal speed (time/distance) were measured in 23 firemen during the exercises, performed either wearing fire protection clothing and SCBA (p2) and service dress (p1). We also measured maximal oxygen consumption (VO2 max, indirect determination), WBGT and the speed/HR ratio (iR) as an arbitrary index of physical work performance. The participant reached the sub-maximal HR in both exercises (p1 87.01%; p2 88.84%). Fire protection devices significantly reduced the exercise maximal speed (p < 0.001) and increased the maximal HR (p < 0.01). IR index was significantly (p < 0.001) lower for p2, indicating a reduction of physical work performance (-26.9%); VO2 max was inversely related with mean and maximal HR (p < 0.001). These results suggest that only well trained firefighters should be employed in emergency actions requiring fire protection devices and SCBA. PMID- 9987616 TI - [The determination of urinary cyclophosphamide at low concentration levels by liquid-liquid extraction and HPLC/MS/MS analysis]. AB - A sensitive, specific and accurate high-performance liquid chromatography-ion spray-tandem mass spectrometry procedure (HPLC/MS/MS) has been developed to quantify cyclophosphamide in human urine. This methodology, which includes the liquid-liquid extraction with ethyl acetate, requires no derivatization procedures, preventing cyclophosphamide from possible thermal and chemical decomposition reactions. This methodology was validated by the use of ifosfamide as internal standard (I.S.). The assay was linear over the range 0 to 3.2 ng mL-1 urine, having a low limit of quantification of 0.2 ng mL-1. The low limit of detection was assessed at 0.05 ng mL-1 urine. This method is characterized by a coefficient of variation < 10%. Standard calibration curves, performed on three different days, had correlation coefficient always greater than 0.998. The intra and inter-day precision were within 11%, and accuracy was included in the range 99-103%. The mean extracted recovery assessed at three different concentrations (0.5, 0.8, 3.2 ng mL-1) was always more than 85%. The extraction efficiency of cyclophosphamide from urine samples was also studied at six different pH values (pH 4, 5, 6, 7, 8, 10). CP gave the maximum extraction efficiency when pH urine solutions was adjusted to 7.0 and somewhat lower at the other considered values. PMID- 9987617 TI - [Occupational exposure to vibration: Raynaud's phenomenon and the vascular response to methacholine iontophoresis]. AB - A homogeneous group of 34 subjects exposed to occupational vibratory stress were studied to determine their vasodilatory response to methacoline. The methacoline was administered by iontophoresis. Methacoline is an acetylcholine derivate with the same pharmacological properties of acetylcholine. The 34 study subjects were divided into 3 groups according to their plethysmographic response to a preliminary cold test: group 1, had a typical Raynaud's response; group 2 had normal response to cold, and group 3 had an "intermediate" response. The subjects in group 1 did not respond to methacoline with vasodilation, suggesting endothelial damage at the arterial and arteriolar level, those in group 2 responded with clear vasodilation, and those in group 3 had an intermediate plethysmographic response to methacoline--modest, slowed vasodilation. Based on the results obtained, the authors believe that the true pathogenetic mechanism is an alteration in the vasomotor stability. This change in circulatory homeostasis occur after a vasoconstrictive stimulus, due to vascular endothelium disfunction, in its turn damaged by vibratory microtrauma. This would be the basis for diminished autonomic vascular regulation, mediated by EDRF at the arterial and arteriolar level. It is also probable that the pathogenesis of Raynaud's syndrome in workers exposed to physical or chemical stress has a similar mechanism. PMID- 9987618 TI - [The clinical evaluation of conservative treatment in patients with the thoracic outlet syndrome]. AB - Conservative treatment of thoracic outlet syndrome is frequently recommended but few studies reporting conservative management are present in literature. Thirteen out-patients with thoracic outlet syndrome (4 males, 9 females) were admitted to a conservative treatment (massage and kinesitherapy) involving the cervical spine and shoulder girdle. All the patients were satisfied with the outcome of the treatment. In particular rest symptoms completely disappeared after treatment in all patients. This study confirms the efficacy of physical therapy in the conservative treatment of patients with thoracic outlet syndrome. Further studies on long-term outcome are needed. PMID- 9987619 TI - [Standard parameters in gait analysis in an Italian multicenter case study]. AB - The study reports the results of a group who, in a multicentric trial, using a gait analysis laboratory Italian made, and a standard procedure, examined 127 normal subjects. The gait laboratory is composed of contacts to relieve the support on the ground, goniometric transducers with an articulated parallelogram, active sensors for cutaneous electromyography, patient unit for data collection and transmission, interface modules for signal reconstruction, software for data elaboration. All data was elaborated in order to give normative data for Italian population. There were no differences between right and left side, nor between male and female subjects. Values of the present study was compared with previous foreign literature and a critical comment is proposed. PMID- 9987620 TI - [A group therapy model in the rehabilitation fo alcoholism]. AB - At present group psychotherapy is one of the most important resources in the treatment of alcoholism. Among the various theoretical orientations present in this setting, the systemic approach has always favoured interventions designed to improve interpersonal relationships. More recently, the concepts of constructivism and "narrative" therapy have laid greater emphasis upon the relational and linguistic aspect of any individual problem. Starting from these premises, a systemic-constructivistic therapy group was created for persons with problems associated with alcohol, as part of an inpatient rehabilitation programme. Given the novelty of this initiative and the particular context, several solutions were adopted that may represent a proposal for the extension of the method. The characteristics and ways in which this particular group might evolve are discussed under four headings: 1) the characteristics of the group, 2) techniques for guiding the group, 3) the role and problems facing the therapist, and 4) the recurrent problems in the life of the group. PMID- 9987621 TI - [The history of bronchial asthma]. AB - The history of bronchial asthma from ancient times is traced. The first accounts of asthma in the ancient Greeks and Romans with clinical descriptions by Aretus of Cappadocia and Aulus Celsus Cornelius are recounted. These are followed by the medieval habits of the Middle East as described by Moises Maimonides. The Renaissance is witness to a new scientific fervor in postulating theories on the pathogenesis of bronchial asthma by van Helmont, Willis and Floyer. The seventeenth and eighteenth centuries will see the discovery of the anatomical foundation of bronchial asthma thanks largely to the technical advances in the diagnostic field by Auerbrugge and Laennec. The allergic nature of bronchial asthma is studied by Salter. S Meltzer's hypothesis of histamine release as the pathogenesis of bronchial asthma leads the way for the twentieth century's leading discoveries. PMID- 9987622 TI - Penetration of ciprofloxacin, norfloxacin and ofloxacin into the aqueous humor using different topical application modes. AB - BACKGROUND: A prospective study was undertaken to determine the transcorneal penetration of three topically applied fluoroquinolones into aqueous humor. METHODS: Cataract patients (n = 224) preoperatively received topically applied gyrase inhibitors (0.3% ciprofloxacin, 0.3% norfloxacin, 0.3% ofloxacin) in two different application modes. In application mode I, patients received on the day before operation 3 x 1 eye drop at 2-h intervals, and on the day of operation 3 drops at 1-h intervals. In application mode II, patients received 9 drops at 15 min intervals on the day of operation only. Just before cataract surgery 50-100 ml aqueous humor was aspirated and stored at -80 degrees C. The HPLC method was used for measuring the concentration. RESULTS: The highest concentrations of all tested antibiotics were measured after the mode of application in which one drop was given every 15 min between 06:00 and 08:00 hours before operation. In this mode, ciprofloxacin achieved a mean aqueous level of 379.8 +/- 327.8 mg/l (range 33-1388 mg/l), norfloxacin 182.1 +/- 118.1 mg/l (range 38-480 mg/l) and ofloxacin 563.9 +/- 372.1 mg/l (range 64-1455 mg/l). These mean concentration are all above the MIC90 of gram-negative bacteria like Proteus mirabilis and Escherichia coli. In some cases the concentrations of ciprofloxacin and ofloxacin, but never norfloxacin, reached therapeutic values above the MIC90 of Staphylococcus aureus and Staphylococcus epidermidis. CONCLUSIONS: The mean concentration value of 0.3% ciprofloxacin and of 0.3% ofloxacin in the aqueous humor reached the MIC90 values of the frequently occurring gram-positive and gram-negative bacteria. Of the currently available topical fluoroquinolones, ofloxacin achieved the highest aqueous humor concentration. Considering the higher antimicrobial activity of ciprofloxacin, both ciprofloxacin and ofloxacin may be useful ophthalmic agents in antibacterial management, but they are not efficient against Streptococcus pneumoniae and Pseudomonas aeruginosa. PMID- 9987623 TI - The contrast characteristic of the pattern electroretinogram depends on temporal frequency. AB - BACKGROUND: The pattern electroretinogram (PERG) amplitude is believed to be linearly related to contrast. In the context of analyzing the effects of media opacities on the PERG, we measured its contrast-amplitude function at various temporal frequencies. METHODS: PERGs were recorded in nine subjects with a checksize of 0.8 degree and a mean luminance of 45 cd/m2. Experiment 1 covered six temporal frequencies [checkerboard pattern onset/offset in a transient (4 Hz) condition and checkerboard pattern reversal at 7, 10, 13, 16, 21 rev/s] at three contrast levels (25%, 50% and 100%). A second experiment covered two frequencies (7 and 21 rev/s) at five contrast levels from 25 to 100%, in a large field (27 degrees x 32 degrees) and a perifoveal condition (central mask of 7.5 degrees radius). RESULTS: Experiment 1: At all temporal frequencies the PERG amplitude increases with contrast, but the shape of the contrast-amplitude function varies markedly: Under transient conditions and at 7 rev/s, the PERG increases linearly with contrast, but this function displays a progressively positive curvature at higher frequencies (P < 0.001). At 21 rev/s a reduction of the contrast from 100% to 50% reduces the amplitude to 1/5. Experiment 2: Experiment 1 was replicated. The amplitude-contrast characteristic was found to be linear at 7 rev/s and smoothly accelerating at 21 rev/s; the same characteristics were found when stimulating the perifoveal area alone. CONCLUSION: This dependency of the contrast characteristic on temporal frequency is contrary to what would be expected from a magno/parvo model. Further, this contrast dependency needs to be taken into account when designing stimuli for use in patients that may have media opacities. PMID- 9987624 TI - The favorable effect of topical betaxolol and timolol on glaucomatous visual fields: a 2-year follow-up study. AB - BACKGROUND: It has been suggested that beta-adrenergic antagonists might have mechanisms of action other than ocular hypotensive effects affecting the visual function in glaucoma patients and that betaxolol might protect the visual field better than others. A randomized, double-blind study was conducted to compare the effects of betaxolol and timolol on visual fields of glaucoma patients. METHODS: Sixty-four glaucoma patients were treated with either 0.5% betaxolol or 0.25% timolol eyedrops twice daily. The Octopus visual field performance was followed up for 2 years and analyzed to find diffuse and localized changes. We analyzed the change in the mean sensitivity (MS) and performed a cluster analysis and clinical assessment of the visual fields in both treatment groups. RESULTS: The mean sensitivity (MS) improved significantly and equally in both treatment groups. There was a tendency towards more improved clusters in the betaxolol group than in the timolol group and more worsened cluster in the timolol group than in the betaxolol group, but the difference was not statistically significant. The clinical assessment also showed no statistically significant difference between the two groups. CONCLUSION: In the present study both betaxolol and timolol had a favorable effect on the visual fields of glaucoma patients. There was no statistically significant difference between betaxolol- and timolol-treated patients either in the change in mean retinal sensitivity or in the change in localized scotomatous areas. PMID- 9987625 TI - Risk factors for visual field damage progression in normal-tension glaucoma eyes. AB - BACKGROUND: This study was carried out to evaluate intraocular or systemic factors associated with the visual field damage progression in eyes with normal tension glaucoma (NTG). PATIENTS AND METHODS: Forty-seven NTG eyes with a minimum follow-up of 5 years were enrolled into the retrospective study. A stepwise regression analysis was performed to correlate the visual field damage progression, expressed as the mean deviation (MD) change per year, with several independent clinical factors including age, history of disc hemorrhage, initial MD, mean intraocular pressure (IOP), peak IOP, diurnal fluctuation of IOP, presence of a beta zone of peripapillary atrophy, and use of Ca(2+)-channel blockers. RESULTS: Statistical analysis revealed that non-use of Ca(2+)-channel blockers (P = 0.01), peripapillary atrophy (P = 0.03) and disc hemorrhage (P = 0.04) were associated with visual loss progression. CONCLUSIONS: Risk factors unrelated to IOP were suggested to be associated with progression of visual field loss. Systemic use of Ca(2+)-channel blockers has a favorable effect on visual field prognosis in NTG eyes. PMID- 9987626 TI - Topical cyclosporin A in Thygeson's superficial punctate keratitis. AB - BACKGROUND: Since September 1994 we have administered topical cyclosporin A 2% (CSA) in a prospective study to patients with Thygeson's superficial punctate keratitis (TSPK). After our promising short-term results we now present medium term data of a larger patient group. PATIENTS AND METHODS: Topical CSA was administered to 52 eyes of 28 patients with TSPK. Forty-two were adult eyes (group I), 10 children's eyes (group II). Starting with 3 drops daily during the 1st month, CSA was reduced to 1 drop every 2nd day within 4 months and stopped after 6 months. RESULTS: Complete suppression of the typical epithelial and supepithelial opacities could be achieved in 71.5% of cases in group I and 40% in group II as long as therapy was administered; the other patients responded only partially or not at all. Recurrences were a problem during tapering off or shortly after cessation of therapy, but they could again be treated effectively with the initial CSA regime. Thirty-one percent of all adult eyes and 20% of all pediatric eyes seemed to have completely healed during the observation time. CONCLUSIONS: In more than two thirds of our adult patients topical CSA 2% suppresses the epithelial and subepithelial opacities for as long as this non steroid therapy is administered. Definite healing seems to be achieved in almost one third of all adult patients. In another one third, long-term low-dose CSA therapy is necessary before complete healing may be expected. Children probably do not respond to therapy as well as adults. Whereas the only therapeutic alternative, i.e. steroid eye drops, have a significant potential for side effects in the long run, no side effects have been known from low-dose CSA eye drops. We regard CSA eye drops as a significant progress in the symptomatic treatment of TSPK. PMID- 9987627 TI - Quantification of blood-aqueous barrier breakdown after photorefractive keratectomy for myopia. AB - BACKGROUND: Photorefractive keratectomy (PRK) using the excimer laser is a well established surgical technique for correction of mild to moderate myopic refraction errors in case of spectacle or contact lens incompatibility. As it is still uncertain whether this procedure causes intraocular inflammatory changes, it was the purpose of this study to quantify breakdown of the blood-aqueous barrier following PRK and to look for possible correlations with clinical parameters. PATIENTS AND METHODS: Aqueous flare was quantified using the laser flare-cell meter after medical pupil dilation preoperatively and on days 1, 3 and 7 as well as 1 month and 3 months following PRK with a 193-nm excimer laser (MEL 60, Aesculap-Meditec) in 37 eyes of 22 patients. The preoperative spherical equivalents were -4.4 +/- 3.1 D (range -1.5 to -8.0 D). Pre-, intra- and postoperative treatment was standardized. RESULTS: Preoperatively, aqueous flare values were 3.9 +/- 0.8 photon counts/ms and showed no significant correlation with the spherical equivalent (p > 0.1). Postoperatively, aqueous flare rise was very small with flare values not significantly higher than preoperative values. All postoperative flare values were below the normal limit (< 8.0 photon counts/ms). Flare was highest on day 3 after PRK surgery. There was no statistically significant correlation between aqueous flare and depth of stromal ablation. The number of aqueous "cells" did not increase following PRK at any postoperative follow-up examination. CONCLUSION: Our results indicate that PRK in mild to moderate myopia does not cause a significant breakdown of the blood aqueous barrier. PMID- 9987628 TI - Effects of dipivefrin and pilocarpine on pupil diameter, automated perimetry and LogMAR acuity. AB - BACKGROUND: A study was carried out to ascertain, in ophthalmologically normal subjects, the short-term effects of dipivefrin hydrochloride 0.1% on visual performance and make comparisons with pilocarpine. METHODS: Twelve normal volunteers aged 20-26 years attended on three occasions. One eye, randomly selected, received one drop of either pilocarpine 2%, dipivefrin or saline 0.9%. High- and low-contrast LogMAR acuity at 6 m and pupil diameter (measured by infra red pupillometry) were recorded at baseline (T0) and at intervals up to 90 min following instillation of drops. Program 30-2 of the Humphrey Visual Field Analyzer (HFA) was run at T0 and at 60 min after treatment instillation (T60). Saline was always instilled at visit 1, to allow for learning effects. On visits 2 and 3 either pilocarpine or dipivefrin was randomly instilled into the treated eye. RESULTS: Pilocarpine significantly worsened the field global indices mean deviation (P < 0.001) and pattern standard deviation (P < 0.01) compared with T0. There was no significant change with dipivefrin. A significant (P = 0.01) pupil dilation from 5.44 mm (SD 0.79) at T0 to 6.19 mm (SD 1.09) at T90 occurred with dipivefrin. Pilocarpine caused significant miosis. No significant changes in LogMAR values were found with dipivefrin. Pilocarpine significantly (P < 0.01) increased LogMAR values (i.e. reduced acuity) compared with dipivefrin. At T30 the mean increase in LogMAR was 0.76 (SD 0.30) for high and 0.83 (SD 0.11) for low contrast. By T90 recovery of acuity was virtually complete. CONCLUSIONS: In normals dipivefrin causes mydriasis but does not affect the central visual field global indices (as assessed by STATPAC), or high- and low-contrast LogMAR acuity. Pilocarpine adversely affects the visual field and both measures of acuity. Knowledge of these effects is of value in glaucoma therapy and when monitoring the progression of visual loss. PMID- 9987629 TI - Evaluation of the Night Vision Spectacles on patients with impaired night vision. AB - BACKGROUND: The Night Vision Spectacles (NiViS) were developed by a consortium of European companies to assist individuals who suffer from impaired night vision. They consist of a head-mounted video camera (input) and binocular displays (output) connected to a portable computer processor, which uses an algorithm to enhance the luminance and contrast of the video image. METHODS: Eighteen patients with impaired night vision were tested, including those with retinitis pigmentosa (7), Usher syndrome (2), fundus albipunctatus (1) and complete (4) and incomplete (4) congenital stationary night blindness. Normal trichromats (3) and typical, complete achromats (2) acted as controls. A battery of tests assessed: visual acuity at 5 m (projection unit) and 1 m (chart) and at high and low contrasts; contrast sensitivity; absolute and increment threshold; the influence of glare; contrast motion detection; and hand-eye performance. The tests were performed, with and without the NiViS, at three adaptation levels: low scotopic (10(-3) cd/m2), high scotopic (10(-2) cd/m2) and mesopic (10(-1) cd/m2). RESULTS: At the low and high scotopic levels, the majority of patients showed improved performance on the visual acuity, contrast sensitivity and motion contrast tests with the NiViS. At the mesopic level, the advantage with the NiViS was greatly reduced, but still present for contrast sensitivity. CONCLUSION: Patients with impaired night vision can benefit from the NiViS when performing tasks involving contrast and motion perception. Those with normal visual fields and retaining good photopic vision will benefit more than those with constricted visual fields and impaired cone vision. Recommendations regarding desirable improvements of the NiViS and suitability for the individual patient are given. PMID- 9987630 TI - The Swedish Retinal Detachment Register. I. A database for epidemiological and clinical studies. AB - PURPOSE: To create a computer-based national register for epidemiological and clinical studies on retinal detachment (RD) for large populations over time. METHODS: A database system was developed for Microsoft Windows 95 and NT platforms to support a multi-user environment, comprising 117 fields (270 parameters). The system is equipped with statistical search programs for statistical differences and dependencies between fields and with graphical display. RESULTS: Information is structured into six subgroups: identification of patient, history of RD, preoperative ocular status, operations, recurrence, and follow-up. Lists of diagnoses, methods and surgical procedures facilitate data input. The drop-out frequency ('null') and follow-up recording are automatically monitored. Mean visual acuity is calculated using logMAR units. Data from the first 1116 patients yield a high RD incidence of 14 per 100,000 inhabitants in an urban area. Mean age at surgery for women was 62.9 years (95% confidence interval 61.54-64.35) and for men 58.3 years (95% confidence interval 57.12-59.42). Myopia was more common before the age of 50 (mean -4.16 D, 95% confidence interval -5.00 to -3.32) than at higher age (mean -0.84 D, 95% confidence interval -1.19 to 0.49). Cataract surgery had previously been performed in 30.8% of the eyes and preoperative macular detachment was present in 52.3%. CONCLUSION: This database register is a useful and powerful tool for population-based studies on epidemiological and clinical parameters of RD. Detailed analyses of retinal reattachment surgery in relation to preoperative findings can be performed in large case materials. PMID- 9987631 TI - Patterns of increased in vivo fundus autofluorescence in the junctional zone of geographic atrophy of the retinal pigment epithelium associated with age-related macular degeneration. AB - PURPOSE: To determine in vivo lipofuscin (LF)-induced topographic variations of fundus autofluorescence in eyes with geographic atrophy (GA) of the retinal pigment epithelium (RPE) associated with age-related macular degeneration (ARMD). METHODS: Fundus autofluorescence was examined with a confocal scanning laser ophthalmoscope (Heidelberg Retina Angiograph) after excitation with an argon laser (488 nm) and detection of the emitted light above 500 nm. Fifty-seven eyes of 38 patients with uni- or multifocal GA associated with ARMD were studied. The findings were compared with 43 eyes with GA secondary to other etiologies, including juvenile macular dystrophies. RESULTS: An increased autofluorescence outside the GA was observed in 47 (82.5%) of 57 eyes with GA associated with ARMD in contrast to 4 (9.3%) of 43 eyes with GA of other causes (P < 0.001). Three different patterns were noted: a continuous band at the margin with variable peripheral extension in 36 eyes (76.6%), a diffusely increased autofluorescence at the entire posterior pole in 6 eyes (12.8%), and small focal spots of increased autofluorescence in the junctional zone in 3 eyes (6.4%). Of 19 patients with bilateral GA, 17 (89.5%) had an identical pattern in both eyes. CONCLUSIONS: The different patterns of autofluorescence in the presence of GA associated with ARMD may reflect variable forms of reactive changes in the surrounding RPE cells, and may indicate the extend of compromised RPE secondary to ageing changes in the outer retina, Bruch's membrane and choriocapillaris. Since GA spreads over time, increased LF accumulation in the junctional zone may precede cell death and may, therefore, be of prognostic value. Knowledge of the topographic variation in LF accumulation is important because heterogeneity may reflect underlying differences in cell kinetics, metabolism and biochemistry. PMID- 9987633 TI - pH-dependent secondary conformation of bovine lens alpha-crystallin: ATR infrared spectroscopic study with second-derivative analysis. AB - BACKGROUND: In order to simulate the usage of different formulations of ophthalmic solution, the protein conformational changes of lens alpha-crystallin in buffer solutions of different pH were investigated. METHODS: The secondary structure of bovine lens alpha-crystallin in different Mcllvaine buffer solutions (pH 2.2, 4.0, 6.0, 7.2 and 8.0) was determined by attenuated total reflection (ATR)/Fourier transform infrared (FT-IR) spectrometry with second-derivative technique. The turbidity of alpha-crystallin in different buffer solutions was observed. RESULTS AND CONCLUSION: The results indicate that alpha-crystallin exists mainly in beta-sheet structure at 1627-1637 cm-1. The conformational components of alpha-crystallin may be closely similar in pH 7.2 buffer solution and in pH 8.0 buffer solution. Once alpha-crystallin dissolved in pH 6.0 and 4.0 buffer solution, the appearance of a component at 1618 or 1620 cm-1, associated with the presence of intermolecular beta-sheet structure or beta-turn structure or amino acid side chains, implied the denaturation of alpha-crystallin, which was even more marked in pH 4.0 buffer solution. Due to the effect of dissociation and stability of alpha-crystallin in pH 2.2 buffer solution, the secondary structure of the intact alpha-crystallin was difficult to evaluate. This study demonstrates that different pH can vary secondary conformational structure of alpha-crystallin, particularly if the pH is below 6.0. This suggests that the secondary structure of alpha-crystallin in buffer solution exhibits pH-dependent characteristics. PMID- 9987632 TI - Quantification of intraocular retained perfluorodecalin after macroscopic complete removal. AB - BACKGROUND: A study was performed to determine the amount of intraocular retained perfluorodecalin after macroscopic complete removal. MATERIAL AND METHODS: Freshly enucleated pig eyes had the anterior segment removed, vitrectomy was carried out, and the eye cups were placed in 0.9% buffered saline solution. One millilitre of perfluorodecalin was instilled for 30 min, followed by a fluid-air exchange. Perfluorodecalin was macroscopically removed. The retina was rinsed twice with 0.9% buffered saline solution. In a second group no rinsing was done, while in a third group no fluid-air exchange was performed. Finally all eye cups were filled with 2.0 ml of the perfluoropolyether Hostinert 130 to dissolve retained perfluorodecalin. The quantity of perfluorodecalin in perfluoropolyether was determined by gas chromatography. RESULTS: Retained perfluorodecalin was detected in all experiments. The smallest portion of perfluorodecalin retained (range 0.04-0.08, mean 0.058%, SD +/- 0.015%) was observed without fluid-air exchange. After fluid-air exchange the portion with rinsing was 0.11-0.27% (mean 0.21%, SD +/- 0.059%) and that without rinsing was 0.51-0.69% (mean 0.60%, SD +/- 0.065%). CONCLUSIONS: Even after macroscopic complete removal of perfluorodecalin a thin layer remains on the retina. If intraoperative fluid-gas exchange is necessary, multiple rinsing with 0.9% buffered saline solution should be performed to reduce the amount of perfluorocarbon liquid retained. PMID- 9987634 TI - PRK-induced anisometropia in the rabbit as a model of myopia. AB - BACKGROUND: Current animal models of myopia, such as the chick and the tree shrew, have characteristics that limit their applicability to human myopia and/or their use among researchers. The purpose of this study was to establish a rabbit model of myopia based on photorefractive keratectomy (PRK)-induced anisometropia. METHODS: A group of five pigmented rabbits was treated with a monocular -5 D PRK at 5 weeks of age. At 10 weeks of age, two of the eyes were retreated with a second -5 D PRK procedure to compensate for partial regression of the refractive effect. A second group of six pigmented rabbits was treated with a monocular -6 D PRK at 10 weeks of age. Longitudinal measurements of corneal curvature, refraction, and axial length were performed until the rabbits were 13 and 21 weeks of age in groups 1 and 2, respectively. The rabbits in each group were from the same litter. RESULTS: Keratometry and retinoscopy measurements confirmed the refractive effect of the PRK procedures. At the final measurement point in group 1, the PRK-treated eyes were significantly longer than the untreated eyes (16.01 +/- 0.45 mm vs 15.45 +/- 0.56 mm). In group 2, the PRK-treated eyes were significantly longer by 0.19 mm and 0.20 mm at ages 19 and 21 weeks, respectively. CONCLUSIONS: PRK-induced anisometropia is an effective technique to induce hyperopic error compensation in the rabbit as a model of myopic development. The technique is effective if the PRK procedure is performed at either 5 or 10 weeks of age. However, after PRK at 5 weeks of age, partial retreatment may be necessary due to regression of the PRK effect. PMID- 9987635 TI - Central serous chorioretinopathy complicating solar retinopathy treated with glucocorticoids. AB - BACKGROUND: Solar retinopathy and central serous chorio-retinopathy are two well defined clinical entities which affect the macular area. Their association has never been described. The relation of central serous chorioretinopathy with the exposure to glucocorticoids has been recently suggested. CASE REPORT: Central serous chorioretinopathy developed in a patient who received corticosteroid therapy for solar retinopathy. CONCLUSION: This case report provides additional evidence that central serous chorioretinopathy may develop under the effect of glucocorticoids. Retinal damage resulting from a previous insult, such as solar retinopathy, may act as the permissive factor. PMID- 9987636 TI - Glass-ionomer cement: evaluation as an orbital implant. AB - BACKGROUND: To assess the potential of a porous glass-ionomer cement (GIC) as an alternative material for spherical orbital implants, the handling, side effects and rates of fibrovascular ingrowth of this material were compared with those of a synthetic hydroxyapatite (HA) implant. METHOD: Twenty-one GIC and 8 HA uncovered 14-mm spheres were implanted into the orbits of New Zealand albino rabbits. Postoperative reactions, animal's behaviour, weight increase and socket conditions were monitored. Light and electron microscopy of the exenterated orbits were performed 2, 3 and 6 months after primary insertion. RESULTS: Implanting of GIC was easier than HA. Postoperatively all animals did well. Three HA and 1 GIC implant caused conjunctival dehiscences, but no implant extrusion was observed. Histologically, both materials caused mild inflammation in the surrounding connective tissue capsule, decreasing with time. GIC implants proved to be not truly porous, with only peripheral pores partly occupied by relatively acellular collagenous connective tissue. Free glass particles were observed in both the connective tissue and giant cells, occupying the partly filled pore spaces. HA implants showed extensive ingrowth of vital host tissue from the beginning. CONCLUSIONS: Considering the clinical findings and the mild inflammation in the connective tissue capsule surrounding both materials, they would appear to be equally well tolerated at the implant site. The significantly different microstructure and the histological results make GIC, despite better handling, less suitable as an orbital implant. PMID- 9987637 TI - Simultaneous assessment of the hemodynamic, cardiomechanical, and electrophysiological effects of terfenadine on the in vivo canine model. AB - Prolongation of the QT interval, sometimes leading to torsades de pointes, has been clinically reported during terfenadine treatment. However, information regarding the cardiovascular profile of terfenadine is still limited, particularly in in vivo animal models. In the current study, we examined the cardiovascular effects of terfenadine using halothane-anesthetized, closed-chest in vivo canine models (n = 6) to better simulate the clinical situation. Intravenous infusion of 0.3 mg/kg of terfenadine over 10 min, which would attain the antihistaminic plasma concentration, reduced the heart rate and left ventricular contractility and prolonged the repolarization period as well as the ventricular effective refractory period. An additional infusion of a ten times higher dose of terfenadine over 10 min caused hypotension and increased left ventricular preload and atrioventricular conduction time, in addition to potentiating the changes observed by the lower dose. A reverse use-dependent prolongation of the repolarization period was observed after the higher dose infusion. Moreover, early afterdepolarization-like potential was detected in four out of six experiments. Since each suppressive effect can become deleterious during terfenadine overdose, caution must be taken for those patients with potential cardiac dysfunction and with the risk of elevated plasma drug concentrations. PMID- 9987638 TI - Acute hemodynamic and coronary circulatory effects of experimental autoimmune myocarditis. AB - Myocarditis and progression to cardiomyopathy is associated with focal spasm and reperfusion of the coronary microcirculation. Experimental autoimmune myocarditis (EAM), induced with cardiomyosin peptide-specific T cells in Lewis rats, was hypothesized to cause acute hemodynamic and coronary vasculature changes. Fifteen experimental animals (5 each at 1, 2, and 3 weeks after T-cell injection) and eight controls were studied using the constant pressure variant of the isolated heart. Coronary resistant decreased while coronary flow increased (P < 0.05) in EAM hearts after the first week. Rate-pressure product, +dP/dt and -dP/dt, decreased while the heart/body weight ratio increased (P < 0.05) compared with controls at 1 week but not at 2 or 3 weeks. Mean local myocardial PO2, which reflects local oxygen delivery and consumption, and MVO2 were not different for EAM hearts. However, compared with controls EAM myocardial PO2 varied more widely and was often beyond the usual range, suggesting the occurrence of localized hypoxic and hyperoxic areas. In summary, after the first week there was a significant decrease in coronary resistance in the EAM animals, which required higher flow to maintain a similar perfusion pressure. These changes in coronary resistance and flow along with the heterogeneity and extremes of local myocardial PO2 levels without a significant change in MVO2 may be explained by postulating development of low-resistance, high-flow hyperoxic areas which steal flow, thus causing hypoxia in other areas. PMID- 9987639 TI - Acetazolamide-induced increase in blood flow to rabbit organs is confirmed using colored microspheres. AB - Inhibitors of carbonic anhydrase activity have been found to increase blood and organ PCO2 and to increase blood flow (BF) in individual organs. To determine whether carbonic anhydrase inhibition coordinately induces an increase in BF in several organs, we assayed the effect of the carbonic anhydrase inhibitor, acetazolamide (AZ), on BF in rabbit organs using the colored microsphere (CM) assay. Eight female white rabbits were anesthetized with ketamine and urethane, and administered three sequential doses of 4 mg/kg AZ. After each dose, the rabbits were injected with 9 x 10(5) CMs of different colors, and arterial blood was collected. We found that AZ had no effect on blood pressure, body temperature, hemoglobin concentration, or PaCO2. In contrast, 12 mg/kg AZ significantly increased PaO2 and significantly decreased base excess. When we measured organ BF, we observed, in response to 12 mg/kg AZ, an 82% increase in brain BF and a 55% increase in kidney BF, but no change in BF of the liver, stomach wall, or abdominal muscle. These findings suggest that the inhibition of carbonic anhydrase activity by AZ, which decreases the rate of CO2 conversion to HCO3-, causes the retention of CO2 in tissues and organs, and thus increases BF in specific organs. Administration of carbonic anhydrase inhibitors, such as AZ, may increase BF to the brain and kidney without reducing PaO2, thereby increasing the supply of oxygen in conditions involving hypoxia such as ischemia and shock. PMID- 9987641 TI - Noninvasive measurement of aortic pressure waveform by ultrasound. AB - At present, the aortic pressure (Pa) waveform can only be measured invasively. In this paper, we describe a new noninvasive method of measuring Pa. The aortic diameter (Da) pulse waveform was measured noninvasively from the suprasternal fossa using an echo-tracking system that was applied to the anterior and posterior aortic wall echoes. To eliminate viscoelastic distortion, the measured Da was converted to an estimate of Pa, named P beta, using the stiffness parameter beta, which revealed the viscoelastic relationship between the vessel diameter and its internal pressure. P beta was then compared with the Pa pattern that was measured directly. Eight patients with ischemic heart disease who had undergone cardiac catheterization were examined by this method. Results showed that (1) the Da and Pa waveforms were similar; (2) the P beta waveform resembled the Pa waveform more closely than did the Da waveforms for a single cardiac cycle (r = 0.970); and (3) in particular, P beta resembled Pa most closely during the upslope phase of the ejection period (r = 0.996). Our results suggest that the Pa waveform can be accurately estimated from noninvasive measurements by this method. PMID- 9987640 TI - Estimation of left ventricular contractile performance in atrial fibrillation: experimental and clinical studies. AB - There are few studies regarding the assessment of left ventricular contractile function in patients with atrial fibrillation (AF). The aim of this study was to assess the left ventricular (LV) contractile function, i.e., the end-systolic pressure-volume relation (Ees) and a recently developed LV systolic myocardial stiffness constant (Ksm), without load manipulation in AF. In an experimental study of acute AF in dogs (n = 5), we were able to assess these indexes of the LV contractile function during acute AF, and found that the values were similar to those obtained during occlusion of the inferior vena cava (IVC) at the baseline state. During rapid ventricular pacing (140 or 160 bpm), the indices of LV contractile function increased due to the force-frequency relation (4.56 +/- 1.85, Ees baseline; 6.42 +/- 2.54*+, Ees pacing; 5.15 +/- 2.01 mmHg/ml, Ees AF; *P < 0.05 vs baseline, +P < 0.05 vs. AF)(4.73 +/- 0.48, Ksm baseline; 6.24 +/- 1.12*+, Ksm pacing; 3.99 +/- 1.14, Ksm AF; *P < 0.05 vs baseline, +P < 0.05 vs AF). In a study of chronic clinical AF in patients without heart disease (lone AF, n = 7), the indexes of LV contractile function were preserved compared with those of control patients (CTL, n = 10) obtained during IVC occlusion; the values were decreased in patients with both AF and dilated cardiomyopathy (AFDCM, n = 5)(2.5 +/- 1.1, Ees CTL; 2.4 +/- 0.4, Ees lone AF; 1.1 +/- 0.3 mmHg/ml*+, Ees AFDCM; *P < 0.05 vs CTL, +P < 0.05 vs lone AF)(5.3 +/- 1.8, Ksm CTL; 4.9 +/- 1.6, Ksm lone AF; 2.7 +/- 0.2*+, Ksm AFDCM; *P < 0.05 vs CTL, +P < 0.05 vs lone AF). Thus, during acute AF in dogs and in chronic AF patients, LV contractile function was assessed without load manipulation. In both the acute AF dogs and the chronic lone AF patients, LV contractile function was preserved, and in the AFDCM patients it was depressed. PMID- 9987642 TI - Forearm vascular responses during semierect dynamic leg exercise in patients following myocardial infarction. AB - We assessed forearm vascular and blood pressure responses to dynamic leg exercise in patients 7 and 28 days postmyocardial infarction. To determine a possible association between abnormal exercise vascular responses and baroreflex dysfunction, integrated and carotid baroreflex sensitivity and forearm vascular responses (during application of subhypotensive lower body negative pressure) were assessed. On day 7, 42 patients were compared with 21 age- and sex-matched controls. All subjects were assessed for (1) forearm vascular resistance during semierect exercise, (2) blood pressure measurements during erect treadmill exercise, and (3) integrated, cardiopulmonary, and carotid baroreceptor sensitivity. These studies were repeated in 13 patients on day 28. Forearm vascular resistance increased during exercise by 36% +/- 63% in patients versus 121% +/- 105% in controls (P = 0.0001), and fell in 15 patients, a response seen in none of the controls. Exercise hypotension was demonstrated in 5 patients, all of whom had abnormal vasodilator vascular responses. Those patients with vasodilator responses had a lower left ventricular ejection fraction (52% +/- 12% vs 62% +/- 9%; P = 0.007), and lower cardiopulmonary mechanoreceptor sensitivity (-6.6 +/- 3.9 units vs +6.4 +/- 10.4 units, P = 0.02) than those with constrictor responses, respectively. In the 13 patients studied on day 28, the change in forearm vascular resistance was similar to that observed on day 7 (36% +/- 63% vs 46% +/- 73%). Paradoxical vasodilation of forearm vessels during leg exercise is common in patients studied 7 and 28 days postmyocardial infarction, and is associated with lower left ventricular ejection fraction and abnormal vascular responses during subhypotensive lower body negative pressure. PMID- 9987643 TI - Thickness, taper, and ellipticity in the aortoiliac bifurcation of patients aged 1 day to 76 years. AB - Lumen area, ellipticity, and wall thickness were measured in the aortoiliac bifurcations obtained at autopsy from 14 patients aged between 1 day and 76 years. The method involved freezing pressure-fixed, stained bifurcations on the stage of a refrigerated microtome and then looking at the block face while sections were removed. Area change was normalized over segment length to produce a value of either taper (narrowing, in mm2/mm), or flare (expansion). The aortoiliac bifurcations were divided into three regions based on the area changes: an apical region corresponding to the bifurcation apex (taper = 2.96 +/- 0.80 mm2/mm), a preapical region (flare = 3.58 +/- 0.87 mm2/mm), and the postapical region (flare = 0.82 +/- 0.80 mm2/mm). Preapical lumen ellipticity showed that the anterio-posterior diameter was always less than the lateral diameter, while the degree of ellipticity increased with age. Average circumferential wall thickness, assessed in polar coordinates, decreased between 0 degree (right lateral) and 120 degrees, while a significant increase in wall thickness was present between 120 degrees and 200 degrees. The most striking difference was found in the 1-day-old, which was very thin posteriorly. This detailed geometric analysis of the aortoiliac bifurcation suggests that taper, flare, and variations in both circumferential and longitudinal wall thickness need to be considered when trying to correlate physical factors in the aorta with the precise location of atherosclerotic lesions and wall remodeling. PMID- 9987644 TI - Epigenetic modulation of differentiation in CE44 teratocarcinoma. AB - Teratocarcinoma is a mixed germ cell tumor histologically composed of embryonal carcinoma cells and embryonic and extraembryonic tissues. In the present work we have used the CE44 teratocarcinoma, which is a tumor cell line derived from the OTT6050 experimental tumor, to appreciate the influence the microenvironment has on the modulation of tumoral differentiation. For this, we have studied the development of CE44 teratocarcinoma in primary tumors (subcutaneous and intrasplenic) and in experimental metastases (hepatic and pulmonary). CE44 teratocarcinoma shows variations in its capacity for differentiation in so far as development is concerned and, in hepatic metastases, we noticed a reparative process of the intratumoral necrotic areas which in the same cases were substituted by loose connective tissue. Our results clearly suggest that the microenvironment is decisive in the biological behaviour of the teratocarcinoma cells and that epigenetic factors influence the capacity for differentiation of the undifferentiated tumoral cells. PMID- 9987645 TI - Development of immune complex trapping: experimental study of lymphoid follicles and germinal centers newly induced by exogenous stimulants in mouse popliteal lymph nodes. AB - The development of immune complex trapping in newly-induced lymphoid follicles of draining popliteal lymph nodes was investigated in young adult mice, which had been given bilateral injection of hemocyanin (KLH) or phytohemagglutinin (PHA), each absorbed onto alumina. HRP-anti-HRP immune complex was injected into the footpad 1 day before sacrifice. Using three series of semi-serial cryostat sections prepared from each popliteal node, the number of lymphoid follicles in each node was counted, and follicular localization of the in vivo injected and in vitro applied immune complexes in each follicle was determined. By day 5, a large germinal center had developed within each preexisting follicle. A large number of 'new' secondary follicles, each containing a small PNA-positive germinal center, appeared outside pre-existing follicles, from day 5 through day 11 in KLH-treated nodes, and from day 7 through day 14 in PHA-treated nodes. Shortly after their appearance, new secondary follicles showed no in vitro or in vivo trapping, but subsequently, many of the new follicles began to display in vitro trapping, at first weakly but later intensely. Occurrence of in vivo trapping in new follicles took some time and was first recognized when new follicles showed intense in vitro trapping. At day 21 or 25, many of the new follicles showed both in vitro and in vivo trapping. It was concluded that in lymph nodes treated with a stimulant, secondary follicles containing germinal centers can be formed de novo in the extrafollicular zone where the follicular trapping microenvironment is absent, but subsequently the microenvironment capable of trapping immune complexes develops at the site of formation of new follicles. PMID- 9987646 TI - The degradation of glycogen in the lysosomes of newborn rat hepatocytes: glycogen , maltose- and isomaltose-hydrolyzing acid alpha glucosidase activities in liver. AB - The lysosomal glucosidase activities and glycogen degradation in newborn rat liver were studied by using biochemical assays, electron microscopy and quantitative morphometry. Glycogen-hydrolyzing, maltose-hydrolyzing and isomaltose-hydrolyzing activities were low at birth but increased afterwards. At the age of 6 hours they were markedly elevated. Actinomycin prevented the development of glucosidase activities indicating that these depend on protein synthesis. Parenteral glucose inhibited all three activities. This was apparently due to the abolition of normal postnatal hypoglycemia and the need for blood glucose. Cyclic AMP increased the glycogen-hydrolyzing but not the maltose hydrolyzing activity. Propranolol inhibited the glycogen-hydrolyzing but not the maltose-hydrolyzing activity. The observations of this study provide further support for the hypothesis made by previous investigators that these activities are due to different enzymes. PMID- 9987647 TI - Age-related changes in antral endocrine cells in mice. AB - Antral endocrine cells in four age groups of mice, namely prepubertal (1 month old), young (3 months old), ageing (12 months old) and senescent (24 months old), were detected by immunocytochemistry and quantified by computerized image analysis. A statistical difference was detected between the different age groups regarding the numbers of gastrin-, somatostatin-, and serotonin-immunoreactive cells. The number of gastrin-immunoreactive cells significantly increased between 1 and 12 months, whereas they became significantly fewer between 12 and 24 months. Somatostatin-immunoreactive cell number increased significantly in 1-, 12 and 24-month-old mice, compared with young mice (3 months old). The number of serotonin-immunoreactive cells also increased significantly in 1- and 12-month old mice as compared with young mice. There was a statistical difference between different age-groups regarding the cell secretory index (CSI) of somatostatin- and gastrin-immunoreactive cells, the CSI of both somatostatin- and serotonin immunoreactive cells increased significantly in 1-, 12-, and 24-month-old mice, compared with young mice. There was no statistical difference between the different age-groups regarding the CSI of gastrin-immunoreactive cells, nor between males and females regarding the number and CSI of all the endocrine cell types investigated. It is suggested that the large number of somatostatin immunoreactive cells in ageing and senescent mice might have an impact on the gastric delay seen in the elderly. It was concluded also that the changes in the antral endocrine cells could be involved in the development of dysfunction of the gastrointestinal tract inherent in ageing, or could be secondary to structural and functional changes in the alimentary tract caused by ageing. PMID- 9987648 TI - Bcl-2 protein expression and gut neurohormonal polypeptide/amine production in colorectal carcinomas and tumor-neighboring mucosa, which closely correlate to the occurrence of tumor. AB - To clarify whether advanced colorectal carcinomas and tumor-neighboring mucosa simultaneously produce both Bcl-2 protein and gut neurohormonal polypeptides and/or amines, and the interrelationship of these phenomenon, we studied retrospective analysis of Bcl-2 protein production and neuroendocrine characteristics in 52 cases of advanced colorectal carcinoma and surrounding mucosa. All of the tumor-neighboring mucosa presented hyperplasia. The rates of enhanced immunoreactivity of the tumor-neighboring mucosa and of positive immunoreactivity of the carcinomas against human Bcl-2 protein and against human vasoactive intestinal polypeptide, pancreatic polypeptide and somatostatin were 78.8% and 94.2%, 82.7% and 59.6%, 78.8% and 67.3%, and 88.5% and 84.6% respectively. Double immunostaining for Bcl-2 protein and each peptide hormone revealed simultaneous expression. In contrast, that of tumor-neighboring mucosa and carcinomas to serotonin and chromogranin-A and to argyrophilia were 11.5% and 1.9%, 32.7% and 17.3%, and 26.9% and 21.2%, respectively. We concluded that tumor neighboring crypt cells displayed not only hyperplasia but also neuroendocrine characteristics and that enhanced Bcl-2 protein immunoreactivity correlated with tumor occurrence in the wall of the colorectum. The production of Bcl-2 protein by tumor cells and tumor-neighboring crypt cells indicates that the bcl-2 protooncogene may act not only as an inhibitor of apoptosis but also as an inducer of neuroendocrine differentiation from the latent characteristics of the endodermal stem cell. PMID- 9987649 TI - Effect of hypertension and captopril treatment on the vasopressin in the rat median eminence and posterior lobe of the hypophysis. An immunohistochemical study. AB - The present study analyses the effects of hypertension and/or its oral treatment with captopril (angiotensine-converting enzyme inhibitor) on the rat median eminence (ME) and the posterior lobe of the hypophysis (PL). After an immunohistochemical reaction using an antibody against arginine-vasopressin, we compared by densitometry the amount of vasopressin immunoreactive material (vasopressin-ir) of these centers in 4 groups of animals: control Wistar Kyoto rats (WKY), spontaneously hypertensive rats (SHR), WKY rats treated with captopril (WKY-T) and SHR rats also treated with the same drug (SHR-T). Captopril was administrated at a dosage of 0.1 mg/ml in the drinking water from the 8th to the 15th weeks. We have found that the rats showing the lowest level of vasopressin-ir, in both ME and PL, were those from the SHR group, the concentration increasing after oral captopril treatment (SHR-T), although without reaching the values of WKY rats. Then, ACE inhibition by captopril influences vasopressin content in brain areas where the hormone is concentrated before being released, which supports the hypothesis that suggests a central modulatory effect of ACE inhibitors, contributing to their therapeutic action on hypertension. PMID- 9987650 TI - Immunohistochemical demonstration of metallothionein in benign and malignant canine mammary tumours. AB - Immunocytochemical demonstration of metallothionein (MT) has been reported as a useful prognostic tool in human breast cancer. The aim of this study was to determine the immunohistochemical location of MT in canine mammary tumours and its possible correlation with the morphologic characteristics of these tumours. Surgical specimens from spontaneous malignant (n = 20) and benign mammary neoplasms (n = 20) were processed for routine histological examination and immunohistochemical study. An indirect immunoperoxidase technique, using monoclonal antibody E9 against horse MT was employed. Intensity of the stain, the percentage of immunoreactive tumour cells and immunohistochemical overexpression of MT was estimated for each case. Metallothionein over-expression, defined as those cases with more than 10% immunopositive cells, was detected in both benign and malignant mammary tumours. However, strong immunostaining intensity was seen in benign tumours, whereas in malignant tumours immunopositive cells stained weakly. Positive MT immunostaining occurred in neoplastic epithelial cells, and some chondrocytes present in mixed mammary tumours. However, staining intensity was variable in immunopositive cells. Differences in staining intensity between the primary malignant mammary tumour, tumour emboli and metastatic cells within a lymph node were also noted. Myoepithelial cells and connective tissue did not stain for MT. We concluded that metallothionein immunostaining cannot be used as a diagnostic or prognostic tool in canine mammary neoplasms. However, results of this study support the hypothesis that MT has a role in tumour proliferation and tumour progression. PMID- 9987651 TI - Effect of neonatal treatment with MSG (monosodium glutamate) on thyroid of the adult male rats. AB - Monosodium glutamate (MSG), administered to newborn rats produces extensive lesions in neurons of the arcuate nuclei of the hypothalamus. The cells represent the site of neurohormone production, including the production of both growth hormone releasing hormone (GHRH) and somatostatin. Studies were performed on male Wistar strain rats, subcutaneously injected with MSG, at 4 mg/g body weight, on days 2, 4, 6, 8 and 10 of life. When the rats reached the age of 18 months, they were additionally stimulated with a single dose of TSH (Ambinon). When the rats reached the age of 6, 12, or 18 months, their thyroids were isolated and fixed in Bouin's solution. In HE-stained preparations, planimetric and volumetric proportions occupied by the epithelial fraction, colloid and stroma, the number of thyroid follicles per mm2 and the thickness of epithelium were determined. Serum T3 and T4 levels were quantified by RIA. Significance of differences was tested using Student's t test. The weight of experimental rat thyroids showed no significant variations as compared to the controls but were greatest in the group of 12-month-old rats. The same was noted for the volumetric fractions of epithelium, colloid and stroma. The planimetric fractions occupied by epithelium, colloid and stroma in the thyroid remained unchanged and amounted to 60%, 31% and 9%, respectively. The number of follicles per mm2 thyroid cross-section in the MSG-treated 6-, 12- or 18-month-old rats was 131.3, 116.2 and 130.4, respectively, and did not differ from control values. Thickness of follicular epithelium showed no significant variations. Serum T3 levels in the rats examined after 6, 12 or 18 months were increased by 67%, 89% and 33%, respectively, as compared to serum T4 levels. When compared to the controls, the serum T4 level was lower only in the 12-month-old MSG-treated rats and the serum T3 level was higher in 18-month-old MSG-treated rats. The ability of the thyroid to respond to Ambinon stimulation was preserved. The results of our investigations suggest that the rat hypothalamic centers involved in regulation of the pituitary-thyroid axis are slightly affected by neonatal administration of MSG. PMID- 9987652 TI - Gold chloride technique to study articular innervation. A protocol validated through computer-assisted colorimetry. AB - We studied variations in gold chloride techniques to elicit neural elements within articular samples, after "in toto" staining. These techniques attempt the differentiation of neural and vascular structures. Major changes in differential staining were observed when the gold chloride concentration was empirically modified. After the rest of the technique was standardized, we selected three gold chloride solutions to perform quantitative color experiments: 1%, 0.75%, and 0.5%. Significant sections of the same thickness were acquired with a digital camera to perform computer-assisted colorimetry. Color was measured through RGB (red-green-blue) channels in vessels, nerves, and background connective tissue as an internal control. By means of multivariate regression analysis, we compared differences in color measurements after 1%, 0.75% and 0.5% gold chloride preparation. Statistically significant coefficients confirmed that red color signals in vessels after the 0.75% and the 0.5% solution were both less intense than after the 1% preparation. Green and blue signals in vessels were also significantly less intense after the 0.5% protocol than after using the 1% solution. Red color signals in nerves between the 1% and the 0.75% preparation protocols were more intense and not significantly different, while the 0.5% preparation produced significantly less intense red signals in nerves. Non significant differences were observed in green or blue signals from nerves after any protocol. We concluded that the 0.75% gold chloride solution protocol produced more intense red signals in nerves and less intense red signals in vessels. This was the most discriminant protocol in our series, based on color signals. PMID- 9987653 TI - Angiogenesis and expression of tenascin after transmural laser revascularization. AB - Transmyocardial revascularization (TMR) with CO2-laser equipment is an alternative approach in the treatment of patients with severe ischemic cardiac disease. Several studies concerning morphological features after TMR document a strong transmyocardial injury, but little is known about wound healing in laser induced alterations of the cardiac skeleton and their putative role for angiogenesis and endothelialization. The present study was conducted to establish a useful immunohistochemical marker for detection of these laser-induced injuries and to analyze starting points of angiogenesis in human myocardium after TMR. Our data show that tenascin labeling is a useful immunohistochemical approach to detect laser-alterated segments of the cardiac skeleton as well as laser-induced fibrosis. Starting points of the angiogenetic process are seen throughout the margins of laser-induced lesions where myocardial capillaries are found. Disrupted vessels located within laser-alterated connective tissue septa are not major starting points for endothelialization of laser-induced lesions and for capillary sprouts. In comparison to laser-induced fibrosis, induction and promotion of angiogenesis by laser radiation is weak. PMID- 9987654 TI - Radial glia and cell debris removal during lesion-regeneration of the lizard medial cortex. AB - Intraperitoneal injection of the neurotoxin 3-acetylpyridine (3AP) induces a rapid degeneration of the medial cerebral cortex (lizard fascia dentata) granular layer and of its zinc enriched axonal projection (lizard mossy fibres). After 6-8 weeks post-lesion the cell debris have been removed and the granular layer is repopulated by neurons generated in the subjacent ependyma. Both processes, neuron incorporation and debris removal, seem to be crucial for successful regeneration. Scavenging processes in the lesioned mammalian CNS are usually carried out by microglia and/or astrocytes. In the lizard cerebral cortex there are no free astrocytes and the only glial fibrillary acid (GFAP) immunoreactive cells are radial glia-ependymocytes, similar to those present during mammalian CNS development. Ependymocytes, in addition to their help in vertical migrations of just generated immature neurons, built the cortical glial scaffold, insulate the blood capillaries, form the outer glial limiting membrane, thus playing an essential role in the lizard cortical blood-brain barrier. In this study, by means of GFAP-immunocytochemistry and electron microscopy, we have shown that radial glial cells participate actively in the removal/phagocytosis of cellular debris generated in the lesion process: mainly degenerated synapses, but interestingly, also some neuronal somata. Cell debris taken up by ependymocyte lateral processes seem to be progressively transported to either distal (pial) or proximal (ventricular) poles of the cell, where they result in lipofuscin accumulations. The hypothetical subsequent exchange of debris from ependymoglia by microglia/macrophages and Kolmer cells is discussed. PMID- 9987655 TI - Microglial cells during the lesion-regeneration of the lizard medial cortex. AB - The lizard medial cortex (lizard fascia dentata) is capable of neural regeneration after being lesioned by the anti-metabolite 3-acetylpyridine (3AP). This study was aimed at detecting microglial behaviour during the medial cortex lesion-regeneration process using tomato lectin histochemistry to label microglia (both with light and electron microscopy) and proliferating cell nuclear antigen (PCNA) immunocytochemistry to label proliferating cells. As expected, 1-2 days post-injection lectin-labelled microglia cells could not be observed in the medial cortex plexiform layers, but later (7 days post-injection) abundant lectin labelled microglia cells re-populated the regenerating medial cortex. Abundant PCNA-immunolabelled nuclei were detected both in the subjacent ependymal neuroepithelium (neuroblasts, maximum at 2 days post-injection) as well as in some parenchymal cells which were also lectin-labelled (microglia, maximum at 7 15 days post-injection). Re-invasive microglia were also detected in the vicinity of ventricular ependymal lining, blood vessels and meninges. The electron microscope demonstrated that these microglial cells participate in cell debris removal, especially of neural granular cell somata. Other cell types related to microglia (mast cells, peri-vascular cells and meningeal cells) were also present during the scavenging process. Significant numbers of microglial cells remained in close relationship with the ependymal proliferative areas, even in control non lesioned animals. This is indirect evidence for the working hypothesis that microglia are not only implicated in cell debris removal, but also in the regulation of newly generated neuroblast incorporation onto the cortical areas. Whether they phagocytose immature neuroblasts or induce cell death in them or even prevent their migration onto the principal layer areas are likely possibilities that remain to be proven. PMID- 9987656 TI - Selective nuclear morphometry as a prognostic factor of survival in renal cell carcinoma. AB - In the present study, we sought to determine the predictive value of selective nuclear morphometry (SNM) for patient outcome in renal cell carcinoma (RCC). Tumor samples of 140 renal adenocarcinomas diagnosed and treated with radical nephrectomy and hilar lymphadenectomy between 1970 and 1988 with a minimum follow up of 5 years in all the cases were studied by SNM. The morphometric analysis was performed in the most malignant tumor selected zone. Selection was based on cytological criteria including nuclear grade. Nuclear morphometric features analyzed were: area, perimeter, major diameter, major and minor diameter of the equivalent ellipse, volume of the equivalent ellipse and sphere, circumference diameter, and shape factors. The results showed that in the selected zone tumor nuclei were larger than in the zones selected at random. There was an inverse correlation between morphometric parameters and survival and a direct one between tumoral grade and stage. Tumors of the long-term survival group of patients presented nuclei with smaller morphometric measurements than tumors of short term survival group, with significant differences between them (p < 0.05). In the survival analysis carried out by the Kaplan-Meier method significant differences existed between different groups formed from break point for: area, perimeter, major diameter, major and minor diameter of the ellipse, volume of the ellipse and sphere, circumference diameter and perimeter shape factor. In the multivariate analysis carried out by the Cox method, the feature with the most predictable value related to survival, was the tumor stage. Morphometric value with the highest punctuation in the test was major nuclear diameter. The rest of the morphometric values (except elliptic shape factor and elongation factor) were also significant but they did not improve prognostic information of the major nuclear diameter. SNM offers a useful aid in a more objective grading of RCC. Multivariate Cox analysis revealed additional value of karyometry to tumor stage. SNM can be a useful tool for stratification of patients with RCC. PMID- 9987657 TI - Etoposide sensitivity of human prostatic cancer cell lines PC-3, DU 145 and LNCaP. AB - Metastatic prostatic cancer is typically refractory to androgen ablation therapy due to the presence of androgen-independent clones in the neoplasia. A therapeutical approach which could effectively control androgen-dependent and independent cells is, thus, needed. Maybe the failure of certain cancer cells to engage in apoptosis could explain the inherent drug resistance of many tumors. Anyway, these cells can retain the ability to undergo apoptosis in response to an adequate stimulus. We tested whether etoposide, a topoisomerase II inhibitor, could induce apoptosis in androgen-dependent (LNCaP) as well as independent (PC-3 and DU 145) human prostate cancer cell lines. Morphological examination was performed, as it is regarded as one of the most reliable parameters for the detection of apoptotic changes. Complementarily, biochemical and flow cytometric studies were also used. Characteristical changes of apoptosis were demonstrated in PC-3, Du 145, and LNCaP cancer cells after treatment with etoposide. These cells, thus, retain the ability to undergo apoptosis under adequate conditions, in a promising approach to hormone refractory prostate cancer therapy. PMID- 9987658 TI - Development of follicular dendritic cells: a study using short-term bone marrow cell grafting in SCID mice. AB - To evaluate the cellular origin of follicular dendritic cells (FDC) in lymphoid follicles (LFs), severe combined immunodeficient (SCID) mice (H-2d) were grafted with 5-bromo-2'-deoxyuridine (BrdU)-incorporated bone marrow cells from CB-17 mice (H-2d) and with non-BrdU-incorporated bone marrow cells from C3H mice (H-2k) and Wistar rats (RT1u). This procedure was followed by antigenic stimulation with horseradish peroxidase and related immune complex (mouse peroxidase anti peroxidase) administration. Secondary LFs in the lymph nodes and spleen of the reconstructed SCID mice were examined morphologically and immunocytochemically. LFs reconstructed with CB-17 mouse bone marrow cells contained FDCs capable of trapping and/or retaining mouse peroxidase anti-peroxidase as immune complexes. Secondary LFs contained BrdU-incorporated germinal center lymphocytes but not non lymphoid stromal cells. A cell grafting study in SCID mice using bone marrow cells from C3H mice and Wistar rats demonstrated that FDCs in reconstructed LFs exhibited a marker specific for the recipient but not for the donor. These data indicate that functionally active FDCs occur de novo in reconstructed LFs in SCID mice, and do not support the view that FDCs originate from bone marrow cells in short-term reconstructed LFs. PMID- 9987659 TI - Possible involvement of DNA methylation in 5-azacytidine-induced neuronal cell apoptosis. AB - Eight chemicals that are cytidine analogues or nucleosides (5-azacytidine (5AzC), 5-azadeoxycytidine, 6-azacytidine, 5-azacytosin, cytidine, 3-deazaadenine, 3 deazauridine and 6-azauridine) were examined for the ability to induce neuronal apoptosis. 5AzC and 5-azadeoxycytidine induced apoptosis in the brain and spinal cord of the fetuses at 24 hr after the injection to dams, while the other chemicals tested failed to induce apoptosis. In the system of PC12 cells, only 5AzC induced apoptosis, and other chemicals failed to provoke morphological and biochemical changes characteristic of apoptosis. 5AzC, 5-azadeoxycytidine and 6 azacytidine failed to induce apoptosis in C6 cells. Gel electrophoresis after MspI or HapII digestions revealed no apparent evidence of DNA demethylation after 5AzC-treatment in either fetal brains or PC12 cells. These results indicate that DNA demethylation is possibly involved in 5AzC-induced neuronal apoptosis although no direct evidence of DNA demethylation was obtained. PMID- 9987660 TI - Antigen retrieval on epoxy sections based on tissue infiltration with a moderately increased amount of accelerator to detect immune complex deposits in glomerular tissue. AB - We wanted to examine the effect of antigen retrieval on epoxy sections where the tissue had been infiltrated by resin containing moderately increased amounts of accelerator. The concentration of accelerator DMP-30 (Tri(Dimethyl Amino Methyl) Phenol) was varied in the range of 0% to 4% in the infiltration step of the tissue processing. Some of the epoxy sections were fixed in osmium tetroxide, and for others this fixative was avoided. Immunogold labeling was performed on epoxy sections and LR-White sections of renal tissue with IgG-deposits, and the antibody used was anti-IgG. Antigen retrieval was performed by heating the sections in citrate buffer. The amount of immunogold labeling on retrieved sections increased according to the amount of accelerator the non-osmicated epoxy sections were based on in the infiltration steps. For the osmicated epoxy sections these differences were less pronounced. The immunogold labeling of retrieved epoxy sections was up to 70% of LR-White labeling. In addition to breaking fixation bond introduced by the chemical fixation, we believe that the antigen retrieval also breaks bonds between the epoxy resin and the embedded tissue. The combination of increased amount of accelerator in the tissue infiltration and antigen retrieval by heating the sections in citrate buffer is a good method for improving the immunolabeling of epoxy sections. PMID- 9987661 TI - The enhancing effect of excess retinol palmitate on induction of odontogenic tumors and inhibitory effect on squamous cell carcinoma of the gingiva in hamsters treated with N-methylnitrosourea. AB - The influence of excess retinol palmitate on induction of tumors in the oral region was examined histopathologically. Sixty-three weanling Syrian golden hamsters were divided into five groups and received either 0.2% N methylnitrosourea (MNU) (1 mg/100 g body weight) or retinol palmitate (RP) (25,000 IU/100 g body weight) twice a week for 16 weeks, singly or in combination. Animals received RP intraperitoneally or intragastrically and then, 6 hours later, the animals received intragastric administration of MNU. To accelerate the cell activity of the incisal tooth buds, intentional disocclusion of the left upper and lower incisor of all hamsters was carried out by repeated cutting with cooled diamond disks to a level just above the inter-dental papilla twice a week for 12 weeks. The right incisors were left in occlusion. In all animals exposed to RP + MNU, while the induction of squamous cell carcinomas of the gingiva and forestomach were prevented, the notable findings were a significantly increased incidence of odontogenic tumors in cut incisal regions of the animals with intragastric administration of RP + MNU and an induction of maxillary neurogenic tumors. The incidence of MNU-induced disturbances in odontogenesis in the incisors was reduced but marked disturbances were increased. RP seemed to have opposite effects of prevention and enhancement for development of neoplastic changes in the oral region. PMID- 9987662 TI - Lectinhistochemistry and ultrastructure of microglial response to monosodium glutamate-mediated neurotoxicity in the arcuate nucleus. AB - In this study we describe the most relevant morphological features of the microglial reaction that takes place in the arcuate nucleus (AN) after neurotoxic injury induced by a single subcutaneous injection of monosodium glutamate (MSG) in neonatal rats. The time course of the reaction was evaluated by lectinhistochemistry. Microglial/macrophagic cells were labelled with the lectin obtained from Lycopersicon esculentum and with B4 isolectin from Griffonia simplicifolia. The microglial response was also studied by ultrastructural observations. The histochemical study revealed the presence of few reactive microglial cells at 6 h post-injection. These cells were intensely stained and had a globular morphology but contained no neuronal debris inside them when observed under the electron microscope. At 12 h post-injection, the number of microglial cells had increased and, at the same time, intense phagocytic activity was observed ultrastructurally. The microglial reaction peaked at 24 and 36 h post-injection, when the number of microglial/macrophagic cells was maximum, although the ultrastructural observations showed that at 36 h the amount of debris ingested by macrophages was decreased with respect to animals sacrificed at 24 h. Finally, at 4 days after neurotoxic injection the number and morphology of microglial cells were similar to those observed in the control rats. The ultrastructural study also revealed the existence of microglial cell mitosis in the territory of the AN together with a strong increase in the number of supraependymal cells resembling macrophages in the third ventricle during the lesion. Our data demonstrate that activated microglial cells initially extend throughout the damaged territory, but from 24-36 h onwards they are especially patent in the ventrolateral portions of the AN. PMID- 9987663 TI - Molecular and cellular basis of tissue remodeling during amphibian metamorphosis. AB - Amphibian metamorphosis involves systematic transformations of various tadpole organs/tissues. Three major types of changes take place during this process. These are remodeling, resorption, and de novo development, all of which appear to involve both cell proliferation and apoptosis (programmed cell death). All metamorphic changes are controlled by thyroid hormone (T3) and are organ autonomous. Recent studies using primary cell cultures and a stably transformed cell line from tadpole tissues have implicated that T3 induces apoptosis cell autonomously. This T3-induced, metamorphosis-associated apoptosis is similar to cell death in other animal species and involves similar cell death executioners. Both the activation of these executioners and the pathways leading to cell proliferation and differentiation are believed to be through transcriptional regulation by T3 receptors (TRs). TRs can activate or repress target gene transcription depending upon the presence or absence of T3, respectively. Many direct T3-response genes have been isolated and found to encode a variety of proteins that can affect both intra- and extra-cellular events. The determinations of the identities of these response genes through sequence analyses and studies on their expression profiles during development have provided strong clues toward their roles in metamorphosis. However, future studies using organ and cell culture systems and/or transient or stable transgenic technologies are required to understand how these genes transduce the T3 signal to activate the downstream cell death and proliferation/differentiation pathways. PMID- 9987664 TI - Cytokines and pulmonary inflammatory and immune diseases. AB - Cytokines are important soluble signalling molecules that dictate and coordinate inflammatory and immune responses. Further understanding the role of cytokines in the pathobiologic mechanisms of pulmonary inflammatory and immune diseases holds the key to the development of effective prophylactic and therapeutic strategies. In the last several years, the use of models of human pulmonary diseases established either in normal adult animals, mice deficient for a given immune cell type or cytokine, or mice engineered to overexpress a given cytokine, has remarkably facilitated our understanding of the mechanisms operating in human disease. Cytokines that are involved in pulmonary inflammatory and immune conditions may be generally divided into groups of pro-inflammatory, anti inflammatory and growth-stimulatory cytokines. While pro-inflammatory cytokines can be detrimental under such severe conditions as endotoxemia and fibrosis, they are required in host resistance against infectious agents. Anti-inflammatory cytokines play an important role in controlling the extent of tissue inflammatory/immune responses. Overexpression of growth-stimulatory cytokines are often directly associated with tissue fibrotic responses. In this review, the findings attained from experimental models by us and others were discussed with emphasis on cellular and histopathologic alterations, cytokine-mediated molecular mechanisms and the prospects of cytokine-based therapeutic strategies. Due to the restrict space, we chose to focus only on models for endotoxic lung, endotoxemia, acute pulmonary infections by extracellular Gram-negative bacteria, chronic pulmonary infections by intracellular myco-bacteria, allergic airways inflammation and pulmonary fibrosis. PMID- 9987665 TI - Systematic review and meta-analysis in anatomic pathology: the value of nuclear DNA content in predicting progression in low grade CIN, the significance of the histological subtype on prognosis in cervical carcinoma. AB - Meta-analysis, though increasingly popular in clinical medicine, has not found acceptance in anatomic pathology. This paper argues that, in combination with a systematic review of the literature, meta-analysis may be usefully applied to pathological research and two examples drawn from gynaecological pathology (the value of nuclear DNA quantitation in predicting progression in low grade cervical intraepithelial neoplasia and the difference in prognosis between squamous cell carcinoma and adenocarcinoma of the cervix) are included to illustrate the methods used and to demonstrate some of the difficulties associated with these techniques. PMID- 9987666 TI - The use of the lectin Helix pomatia agglutinin (HPA) as a prognostic indicator and as a tool in cancer research. AB - Progress in treatment for cancer has enabled extension of the disease-free interval, and of the quality of life for patients, but there has been very little improvement in overall survival rates. The main reason for this has been the ineffectiveness of current therapies to kill all the cancer cells once they have spread to distant sites to form metastatic deposits. One marker which has proved to be useful in identifying those cancers which have the potential to spread is the lectin Helix pomatia agglutinin (HPA). In clinical studies, HPA binding to primary tumours in tissue sections has been of prognostic value in breast, colon and gastric cancer, while no prognostic significance for HPA could be detected in tumours of the head and neck. These studies hence indicate that HPA is best suited to recognise a glycotope on adenocarcinomas. In several studies, HPA reactivity is equal or superior to other classical markers of metastatic potential. Since HPA is a marker of prognosis at the level of individual tumour cells, human tumour cell lines were screened for their HPA positivity. When transplanted into severe combined immunodeficient (scid) mice, HPA positive human breast and colon cancer cells metastasised while HPA negative cancer cell lines in general did not. In order to define HPA binding glycotopes at the molecular level, isolated cell membrane glycoproteins were exposed to labelled HPA on nitrocellulose membranes after Western blotting procedure. The majority of the isolated cell membrane glycoproteins bound HPA indicating that not a single HPA binding glycoprotein exists, which is associated with the metastatic phenotype. Functional investigations using the human/scid mouse chimeras will aid in the identification of those HPA positive glycoproteins which are functionally involved in the metastatic cascade. PMID- 9987667 TI - Proteinase-antiproteinase imbalance in the pathogenesis of emphysema: the role of metalloproteinases in lung damage. AB - Pulmonary emphysema refers to a lung disorder characterized by a diffuse destruction of the alveolar walls resulting in enlargement of the distal airspaces. The disease is usually a chronic, progressive, and disabling disorder. The concept of proteinase/antiproteinase imbalance evolved from the identification of patients with alpha 1-antytripsin deficiency, and from the development of experimental emphysematous lesions using different enzymes. For a long time, this concept was seen as an elastase/antielastase imbalance, with the consequent degradation of elastin. Recent evidence, however, suggests that an intricate process of pulmonary remodeling occurs during the development of emphysema, where a complex network of serine proteases and metalloproteinases capable of degrading different extracellular matrix molecules, primarily, but not exclusively fibrillar collagens and elastin, are implicated in the pathogenesis of this disease. PMID- 9987668 TI - New insights into the function of noncoding RNA and its potential role in disease pathogenesis. AB - All polyadenylated RNAs expressed in mammalian tissues are assumed to be transported to the cytoplasm where they direct the synthesis of a protein product. This mainstream view of the function of polyadenylated transcripts is currently being challenged by the identification of a novel class of genes which, although they encode polyadenylated RNA, do not make a translated protein. Many of these noncoding RNAs are developmentally regulated or show highly restricted patterns of gene expression, and their functions are providing important insight into RNA-based mechanisms of gene expression, genomic imprinting, cell cycle progression, and differentiation. The purpose of this review is to discuss the current understanding of mammalian noncoding RNAs, and to highlight their potential for identifying new pathways of human disease. PMID- 9987669 TI - Nitric oxide synthase in skeletal muscle fibers: a signaling component of the dystrophin-glycoprotein complex. AB - The present review deals with the anatomical distribution, physiological importance, and pathological implications of the neuronal-type nitric oxide synthase (nNOS) in skeletal muscle. Throughout the body, nNOS is located beneath the sarcolemma of skeletal muscle fibers. In rodents, nNOS is enriched in type IIb muscle fibers, but is more homogenously distributed among type II and type I fibers in humans and subhuman primates. It is accumulated on the postsynaptic membrane at the neuromuscular junction. An increased concentration of nNOS is noted at the sarcolemma of muscle spindle fibers, in particular nuclear bag fibers, which belong to type I fibers. The association of nNOS with the sarcolemma is mediated by the dystrophin-glycoprotein complex. Specifically, nNOS is linked to alpha 1-syntrophin through PDZ domain interactions. Possibly, it also directly binds to dystrophin. The activity and expression of nNOS are regulated by both myogenic and neurogenic factors. Besides acetylcholine, glutamate has also been shown to stimulate nNOS, probably acting through N-methyl D-aspartate receptors, which are colocalized with nNOS at the junctional sarcolemma. Functional studies have implicated nitric oxide as a modulator of skeletal muscle contractility, mitochondrial respiration, carbohydrate metabolism, and neuromuscular transmission. A clinically relevant aspect of nNOS is its absence from the skeletal muscle sarcolemma of patients with Duchenne muscular dystrophy (DMD). A concept is presented which suggests that, as a consequence of the disruption of the dystrophin-glyoprotein complex in DMD, nNOS fails to become attached to the sarcolemma and is subject to downregulation in the cytosol. PMID- 9987670 TI - Epithelial integrity, cell death and cell loss in mammalian small intestine. AB - In recent years, the different mechanisms of epithelial cell loss which occur in mammalian and avian small intestine have been re-investigated. Information is now available for a variety of mammalian types and mechanisms can be divided into two major classes: [i] those preserving epithelial integrity by maintaining intercellular tight junctions throughout early-to-late stages of cell extrusion; and [ii] those which compromise integrity by introducing breaches in epithelial continuity. Both classes are associated with the activity and/or proximity of non epithelial cells (mainly lymphocytes and mononuclear phagocytes) located in the epithelium or underlying lamina propria. Intraepithelial lymphocytes may be involved in enterocyte targetting and killing whilst lamina propria (LP) macrophages sequester cell debris. Where epithelial integrity is maintained, two types of loss can be identified. In the first (type 1), complete cells are extruded into the lumen. In the second (type 2), only anucleate apical cell fragments pass into the lumen. There are two variants of type 2 loss distinguishable by the fate of the nucleated basal portions of cells. One variant (type 2a) creates large intercellular spaces extending from the preserved apical cap to the basal lamina and containing enterocyte debris for phagocytosis. The second (type 2b) involves the gradual shrinkage of individual cells (which become more electron-dense) and in situ degeneration of their nucleated subapical portions in increasingly narrower intercellular spaces between adjacent healthy enterocytes. The mechanism of removal of these fragments is unclear but may be via macrophages or surrounding enterocytes. Apoptosis has been implicated in both type 1 and type 2 extrusion. In contrast, type 3 loss involves morphological changes in enterocytes which are reminiscent of those seen in necrosis and is accompanied by breaks in epithelial continuity following cell swelling, a decrease in cell electron density and total or subtotal degradation of organelles and membranes. It ends in loss of either an abnormal cell apex (with subsequent exposure of the degraded cell contents and their spillage into the lumen) or a complete cell remnant (extruded into the lumen before total disintegration of plasma membranes). PMID- 9987671 TI - Molecular genetics of ovarian carcinomas. AB - The phenotypic variability of epithelial ovarian neoplasms correlates with a diversity of changes at the molecular level. Invasive serous and undifferentiated ovarian carcinomas are characterized by p53 mutations with p53 protein accumulation, extensive loss of genetic material of chromosome 17 and complex changes on many other chromosomes, e.g. amplification of oncogenes. These alterations are seen only in a minority of mucinous and endometrioid carcinomas, mainly in advanced stages. Overexpression of bcl-2 is seen most frequently in endometrioid carcinomas (ca. 90% of cases), which in addition show microsatellite instability in around a third of the cases, as has been described in endometrioid endometrial carcinomas. KRAS mutations are characteristic for mucinous LMP tumors and mucinous carcinomas (40-50% of cases) and are also found in a third of serous LMP tumors. In addition, serous LMP tumors show mild microsatellite instability in 30%. However, complex chromosomal aberrations are never seen in these neoplasms. PMID- 9987672 TI - Clinical applications of detecting dysfunctional p53 tumor suppressor protein. AB - The p53 gene encodes for a protein, p53, which plays a critical role in controlling the cell cycle, in DNA repair and in programmed cell death (apoptosis). p53 is one of the most frequently mutated genes in human neoplasms and a variety of techniques have been developed to detect these mutations. These range from advanced molecular-genetic analyses to immunohistochemical staining for the p53 protein. This review will summarize our current understanding of the function of p53 as well as current methods to detect dysfunctional p53 and the clinical value of such analyses. PMID- 9987673 TI - Thrombospondin-1, PECAM-1, and regulation of angiogenesis. AB - Thrombospondin-1 (TSP1) is a multidomain glycoprotein expressed by many cell types. It is a multifunctional protein with important roles in regulation of vascular cell functions. Mutation or loss of tumor suppressor genes results in down regulation of TSP1 expression during malignant transformation. Thus, suggesting that down regulation of TSP1 may contribute to development of the tumor angiogenic phenotype and perhaps tumor metastasis. TSP1 was demonstrated to be a natural inhibitor of angiogenesis. Peptides from procollagen-like domain and type 1 repeats of TSP1, like whole TSP1, inhibit the angiogenic response to a variety of angiogenic stimuli in vivo and endothelial cell (EC) migration in vitro by directly acting on ECs. The molecular mechanisms which mediate these inhibitory effects of TSP1 and its peptides are not understood. TSP1 expression is down regulated in the Polyoma middle T transformed mouse brain ECs (bEND.3). This may remove the TSP1 inhibitory effects allowing ECs to rapidly proliferate in culture and form hemangiomas in vivo. Re-expression of TSP1 in bEND.3 cells restores a normal phenotype and suppresses their ability to form hemangiomas. This is mediated by modulating expression of several genes in concert favoring a differentiated state of endothelium. TSP1 transfected bEND.3 cells down regulate expression of PECAM-1, a multifunctional endothelial cell adhesion molecule with essential roles in angiogenesis. A similar phenotype to that of TSP1 transfected cells was observed when endogenous PECAM-1 levels were down regulated by anti sense transfection of bEND.3 cells. The anti-sense PECAM-1 transfected cells turn on expression of endogenous TSP1 and its angioinhibitory receptor, CD36. Expression of other genes with potential roles in regulation of EC phenotype were also affected in patterns very similar to those observed in TSP1 transfected bEND.3 cells. Therefore, it appears that a reciprocal relationship exists between TSP1 and PECAM-1 such that they are constituents of a "switch" that regulates in concert many components of the angiogenic and differentiated phenotype of ECs. PMID- 9987674 TI - Activin: a novel player in tissue repair processes. AB - Recent studies have demonstrated a strong expression of activin in repair processes of various tissues and organs, including the skin, the lung, the intestine, the cardiovascular system, and even the brain. Although little is as yet known about the function of activin in tissue repair, first results suggest a role of activin in epithelial differentiation, fibroblast proliferation and expression of matrix molecules by these cells, and also in neuroprotection. Whereas a transient overexpression of activin after tissue injury might be beneficial for the repair process, sustained expression of activin could lead to fibrotic processes. Therefore, the modulation of the availability or biological activity of activin could be of particular importance for the treatment of impaired tissue repair on the one hand and tissue fibrosis on the other hand. PMID- 9987675 TI - Intracellular cholesterol trafficking. AB - The overall picture of intracellular cholesterol trafficking is very complex. The transfer of cholesterol within the cell depends on the contribution of several trafficking mechanisms. The known elements of cholesterol trafficking machinery include clathrin-coated pits, scavenger receptor type B1, caveolae, phospholipid rafts, Niemann-Pick C disease protein, sterol carrier protein 2, multidrug resistance protein, microsomal triglyceride transfer protein and steroidogenic acute regulation protein. Several pathways of intracellular cholesterol trafficking, for example retroendocytosis and cholesterol absorption in the intestine, are yet to be connected to specific structural elements. The contribution of different pathways depends on cell type, the source and destination of cholesterol and cellular cholesterol content and requirements. Some pathways are found in most, if not all, cell types, while others are associated with the specialized function of a particular cell type, for example, lipoprotein assembly in the liver or intestine and steroid hormone synthesis in steroidogenic tissue. Certain routes of intracellular cholesterol trafficking are heavily backed up by several auxiliary pathways, others entirely depend on a single functional element. In this review we describe the intracellular machinery involved in the intracellular transfer of cholesterol and give an overview of both the general and specialized pathways of intracellular cholesterol trafficking known to date. PMID- 9987676 TI - Lipid signaling and cell responses at the nuclear level. AB - The nucleus is known to be a site for an active lipid metabolism. Although phospholipids are present in the nuclear envelope, evidence suggests that they are also located further inside the nucleus. The function of these intranuclear lipids has escaped clarification for many years. Early experiments showed that they can interact with DNA double helix affecting its thermal stability and can influence RNA synthesis in isolated nuclei. However, in the last 10 years several investigations have suggested that they may be involved in signal transduction pathways at the nuclear level and a growing body of evidence supports this hypothesis. PMID- 9987678 TI - Apoptosis and autoimmune disease. AB - The process of programmed cell death or apoptosis was already noted in 1842 by Vogt [1], but it was not until the more recent studies of Kerr et al. 1972 [2] that an explosion of interest in apoptosis research occurred. Genetic, biochemical and cellular analysis in certain mammals, in the nematode Caenorhabditis elegans and in the fruitfly Drosophila melanogaster have identified several apoptosis regulating genes. This indicates that programmed cell death is an active, genetically controlled process. Many of the known cell death regulators are homologous in mammals, nematodes and insects, indicating that apoptosis is an evolutionarily conserved process. Apoptosis can be induced via multiple independent signalling pathways which converge upon a common final effector machinery. This stimulates activation of latent cysteine proteases (caspases), which cleave vital cellular substrates and thereby lead to the death of cells. The regulatory pathways of apoptosis are becoming clear with the discovery of specific signalling molecules. It has become evident that many disease processes including autoimmunity and cancer can be caused by deregulation of the apoptotic process. With the discovery of novel cell surface-bound death receptors, their ligands and further insight into the apoptotic machinery within the cell, research may ultimately lead to the design of therapies that allow intervention in the apoptotic process. The aims of such strategies would be to turn on apoptosis in neoplastic cells or in lymphocytes that are causing autoimmune disease or to prevent cell death in degenerative disorders. This review describes current understanding of the molecular regulation of apoptosis, and focuses on issues relating to possible roles of defective cell death control in autoimmunity. PMID- 9987677 TI - Opioids, NSAIDs and 5-lipoxygenase inhibitors act synergistically in brain via arachidonic acid metabolism. AB - We have established that mu-opioid receptor activation causes a presynaptic inhibition of neurotransmitter release that is mediated by 12-lipoxygenase metabolites of arachidonic acid in midbrain neurons [1]. We further demonstrated that the efficacy of opioids was enhanced synergistically by treatment of brain neurons with inhibitors of the other major enzymes responsible for arachidonic acid metabolism; cyclooxygenase (COX-1) and 5-lipoxygenase. These findings explain a mechanism of analgesic action of NSAIDs in the central nervous system that is both independent of prostanoid release and inhibited by opioid antagonists, as well as the synergistic interaction of opioids with NSAIDs. These findings also suggest new avenues for development of centrally active medications involving combinations of lowered doses of opioids and specific 5-lipoxygenase inhibitors. PMID- 9987679 TI - Cytokine-induced sequential migration of neutrophils through endothelium and epithelium. AB - OBJECTIVE AND DESIGN: To better understand the mechanisms by which cytokines induced neutrophils to migrate into the airways, we constructed a novel in vitro model system. MATERIALS: Human umbilical vein endothelial cell (HUVE) monolayers were grown on top of permeable filters and human lung type II-like alveolar epithelial cell (A549) monolayers were grown on the undersurface of the filters. METHODS: The sequential migration of human neutrophils through the endothelium (apical to basal movement) and subsequently through the epithelium (basal to apical movement) in response to IL-1 beta or TNF alpha located basally to the epithelium was measured. RESULTS: We found that IL-1 beta and TNF alpha induced dose-responsive and time-dependent migration through the double monolayers-filter complex. The pattern of migration was similar, and the amount greater than or equal to that observed through either single monolayer/filter complex. Neutrophil migration through naked filters was generally less than that observed through the cellular barriers. The contribution of the monolayer orientation was also examined and found to favor the more physiologic directional migration of neutrophils through an endothelial and epithelial barrier, apical to basal and basal to apical, respectively. In contrast, FMLP-induced neutrophil migration was not dependent upon either the orientation or presence of the monolayer(s). CONCLUSIONS: Thus, we have established an in vitro model system to examine cytokine-induced sequential migration of neutrophils through endothelium and the respiratory epithelium in a manner analogous to that occurring with an in vivo airway stimulus causing neutrophil-rich airway inflammatory responses. PMID- 9987680 TI - The effect of in vitro activation and platelet interaction on the CD9 distribution and adhesion properties of human eosinophils. AB - OBJECTIVE AND DESIGN: The redistribution of CD9 in peripheral blood eosinophils was investigated with respect to the interaction with platelets during in vitro activation, and whether this interaction exerts influence on eosinophil adhesion properties. MATERIALS AND METHODS: Flow cytometry was used to investigate the CD9 expression in purified eosinophils or eosinophils from different whole blood preparations, with or without platelets present. To confirm an eosinophil/platelet interaction fluorescence microscopy was used, and to demonstrate release/shedding of CD9 molecules a biosensor technique was performed. RESULTS: Our results show that both intracellular and surface expression of CD9 decrease upon in vitro activation in the absence of platelets, a phenomenon probably caused by release/shedding of soluble forms of CD9 and not due to intracellular degradation. Increased expression of CD9 on eosinophils, stimulated in the presence of platelets, is partly a result of interacting platelets, judged by the increase in platelet specific marker CD61. In our adhesion assay a significant increase in eosinophil adhesion properties to fibronectin was obtained when eosinophils were PMA stimulated and interacting with platelets, as compared to activated eosinophils without platelets. CONCLUSIONS: Our findings, that CD9 expression on eosinophils is dynamically regulated, support our previous suggestion that CD9 may be a useful activity marker and that platelet interaction acts on eosinophil adhesion. PMID- 9987681 TI - Cytosolic phospholipase A2, increased and activated in the eosinophils of patients with hypereosinophilic syndrome in vivo, is involved in the augmented release of leukotriene C4. AB - OBJECTIVE: Eosinophils from patients with hypereosinophilic syndrome (HES) showed augmented release of leukotriene C4 (LTC4) by stimulation with A23187. In the present study, we investigated the involvement of cytosolic phospholipase A2 (cPLA2) in this phenomenon. METHODS: Eosinophils from normal and HES donors (2.5 x 10(6) cells/ml) were incubated with A23187 (0.03-3 microM) for 60 min in the presence or absence of a cPLA2 inhibitor, AACOCF3. The LTC4 released from eosinophils was measured by enzyme immunoassay. Distribution of cPLA2 and 5 lipoxygenase (5-LO) proteins within the eosinophils were detected by Western immunoblotting. RESULTS: The level of LTC4 released from the HES eosinophils by stimulation with A23187 was higher than that from normal eosinophils. The A23187 induced LTC4 release was inhibited by AACOCF3 in a dose-dependent manner. The amounts of cPLA2 seemed to be increased in the non-stimulated HES eosinophils by an analysis of immunoblotting. To be noticed was that cPLA2 was detected as a phosphorylated and membrane-bound form in the HES eosinophils, but not in the normal eosinophils. In contrast, localization of 5-LO within the eosinophils under A23187 stimulation was not different between normal and HES donors, while the amounts of 5-LO also seemed to be increased in the HES eosinophils. CONCLUSIONS: These results suggest that cPLA2, increased and activated (phosphorylated and membrane-translocated) in vivo, is involved in the augmented release of LTC4 from the HES eosinophils. PMID- 9987682 TI - Temporal relationships between leukocytes, IL-5 and IL-8 in guinea pig lungs, plasma cortisol and airway function after antigen challenge. AB - OBJECTIVE AND DESIGN: The aim was to determine the time courses for the changes in airway function, airway reactivity, influx of inflammatory cells and levels of the pro-inflammatory cytokines, interleukin (IL)-5 and IL-8 in bronchoalveolar lavage fluid (BALF), and the plasma levels of cortisol and ACTH after antigen challenge to determine whether a temporal link could be established between these events. METHODS: Airway function was measured as specific airway conductance (sGsw) in conscious ovalbumin (OvA)-sensitized guinea pigs using whole body plethysmography at intervals after an inhalation challenge with ovalbumin (0.5% for 10 min). Airway responses to the inhaled spasmogen, U46619 (30 ng/ml, 60 s), were measured at 3, 6 and 24 h after challenge. In separate animals, bronchoalveolar lavage fluid (BALF) was obtained after anaesthetic overdose either before challenge or at 1, 3, 6, 12, or 24 h after OvA challenge. Total and differential cell counts of eosinophils and neutrophils were performed on BALF and levels of IL-5 and IL-8 determined by scintillation proximity assays and ELISA, respectively. Plasma cortisol and ACTH levels were determined by RIA kits in blood removed by cardiac puncture at intervals after challenge. RESULTS: An early phase bronchoconstriction occurred which resolved by 3 h and was followed by a late phase between 17 and 24 h. Airway hyperresponsiveness to inhaled U46619, was evident at 3, 6 and 24 h after antigen challenge. Increased IL 5[BALF] was observed by 60 min post challenge implicating a performed storage site. In contrast, IL-8[BALF] was not raised until 3 h post challenge. There was a significant infiltration of neutrophils and eosinophils by 3 and 6 h, respectively. IL-5[BALF] further increased up to 24 h, during the appearance of the late phase of bronchoconstriction and whilst eosinophilia was maximal. Plasma cortisol levels were increased 1 and 3 hours after antigen challenge, thereafter returning to baseline levels. CONCLUSIONS: The hyperresponsiveness appears to be dissociated from the appearance of eosinophils in lavage fluid. The early appearance of IL-5, however, could be a trigger for the migration of eosinophils and development of hyper-responsiveness. The increased plasma cortisol levels occurring after antigen challenge were presumably due to the stress involved and these would be expected to exert an endogenous anti-inflammatory effect. PMID- 9987683 TI - Synergistic protection against cartilage destruction by low dose prednisolone and interleukin-10 in established murine collagen arthritis. AB - OBJECTIVE: To investigate potential synergy of low dosages glucocorticosteroids (GC's) and interleukin-10 (IL-10), using established murine collagen-induced arthritis (CIA) as a model. METHODS: DBA-1J/BOM mice were immunized with bovine type II collagen and boosted at day 21. Mice with established CIA were selected and treated for at least 7 days with either prednisolone (0.05-5 mg/kg), IL-10 (0.1-5 micrograms/day) or the combination of prednisolone/IL-10 (0.05/1 and 0.05/5). Arthritis score was monitored visually, and joint pathology was examined by histology, and serum cartilage oligomeric matrix protein (COMP) measured. RESULTS: Amelioration of CIA was found with dosages of 1 and 5 mg/kg prednisolone, while a dose of 0.05 mg/kg prednisolone was ineffective. Treatment of CIA with 5 micrograms/day IL-10 resulted in a mild, but significant suppression. Synergistic effects were seen with the combination of low dose prednisolone and IL-10 (0.05 mg/kg, 1 microgram/day). Both arthritis score and joint pathology were significantly reduced. Moreover, COMP levels were significantly decreased after IL-10/prednisolone treatment, confirming decreased cartilage involvement. Of great interest, treatment of CIA with prednisolone/IL 10 markedly reduced IL-1 beta and enhanced IL-10 production by synovial tissue. In addition, synovial mRNA levels for IL-1 beta were decreased, while mRNA levels for IL-10 and IL-1Ra were upregulated by combined treatment. CONCLUSION: This study demonstrates synergistic effects of combined treatment with prednisolone and IL-10 on suppressing disease activity of CIA as well as reducing cartilage. PMID- 9987684 TI - Influence of interleukin-1 beta on bradykinin-induced responses in guinea pig peritoneal macrophages. AB - OBJECTIVE AND DESIGN: The endogenous nonapeptide bradykinin is implicated in the pathogenesis of a number of inflammatory diseases. Recently, it could be shown that bradykinin is a potent stimulus for the generation of arachidonic acid, prostaglandin E2 (PGE2) and superoxide radical via the bradykinin B2 receptor from macrophages depending on their stage of maturation or activation. The present study was designed to characterize the effect of the proinflammatory cytokine interleukin-1 beta (IL-1 beta) on responsiveness of macrophages to bradykinin. MATERIAL: Guinea pig peritoneal macrophages were collected 7 days after i.p. injection of paraffinum subliquidum. RESULTS: The bradykinin-induced increase in cytosolic free calcium concentration ([Ca2+]i) and activation of the respiratory burst were significantly enhanced by interleukin-1 beta (100 U/ml) added to cultures of macrophages 24 h before stimulation with bradykinin. However, the EC50 values of bradykinin-induced calcium signal of 23 +/- 8 nM and 29 +/- 17 nM and superoxide radical formation of 64 +/- 22 nM and 34 +/- 29 nM in control and interleukin-1 beta-treated cells, respectively, were not changed. In contrast to the influence of IL-1 beta on these functions, saturation and competition experiments measured by binding of [3H]bradykinin ([3H]BK) to intact macrophages demonstrate that cell exposure to interleukin-1 beta for 24 h caused no change in the density and affinity of the bradykinin B2 receptors. CONCLUSIONS: The most likely explanation for the cytokine effects is an influence on the level of the receptor-effector coupling downstream of the agonist binding. PMID- 9987685 TI - The transfer of two embryos instead of three to reduce the risk of multiple pregnancy: a retrospective analysis. AB - PURPOSE: Our purpose was to investigate whether a reduction in the number of embryos transferred from three to two would help reduce the incidence of multiple pregnancies and yet leave the pregnancy rate unaffected. METHODS: Women were treated in a routine clinical in vitro fertilization program and the results analyzed retrospectively. RESULTS: There was no reduction in the pregnancy rate when two embryos were transferred compared with three. Indeed, there was actually an increase in pregnancy rate after the transfer of two embryos in those cases with one or more embryos remaining after the transfer. CONCLUSIONS: The transfer of only two embryos compared to three in women younger than 40 years of age does not compromise the chance of pregnancy. Triplets were not seen in the limited series of patients when only two embryos were transferred, but the incidence of twins remained the same. Further consideration should be given to strategies that enable the transfer of single embryos without compromising the pregnancy rate. PMID- 9987686 TI - On the reduction of high-order multiple pregnancies. PMID- 9987687 TI - Midtrimester maternal serum screening after multifetal pregnancy reduction in pregnancies conceived by in vitro fertilization. AB - PURPOSE: Data about the effect of multifetal pregnancy reduction on midtrimester maternal serum levels of alpha-fetoprotein (AFP), human chorionic gonadotropin (hCG), and unconjugated estriol (uE3) are scarce and contradictory. Differing gestational ages at fetal reduction, transvaginal versus transabdominal needle insertion, and injection of different feticidal agents compound the analysis of published data. METHODS: We examined clinical and laboratory data about 27 high order gestations that were reduced to twins in the first trimester. Fetal reductions were performed transabdominally at 11.41 +/- 1.15 weeks' gestation by fetal intrathoracic injection of KCl, and maternal blood sampling was performed at 16.48 +/- 1.05 weeks. "Pseudo-risks" for singleton pregnancies were calculated by correcting serum analyte levels for twins. RESULTS: Twenty-four (88.9%) of 27 patients had maternal serum AFP levels above 2.0 MoM (mean, 4.60 +/- 3.48 MoM; range, 1.49-14.85 MoM), however, none of the newborns had structural anomalies. AFP serum levels did not correlate with the number of reduced fetuses or with adverse obstetric outcome. The mean hCG levels were 1.22 +/- 0.49 MoM (range, 0.14-2.47), and the mean uE3 levels were 1.15 +/- 0.31 MoM (range, 0.56-1.84). Based on maternal age alone, seven patients (25.9%) would have been offered amniocentesis for a term Down syndrome risk greater than 1:384, whereas combined risk calculations with hCG and uE3 levels resulted in 1 (3.7%) screen-positive case (P < 0.01). PMID- 9987688 TI - Use of a medium devoid of any human or animal compound (SMART2) for embryo culture in intracytoplasmic sperm injection. AB - PURPOSE: Our purpose was to evaluate the efficiency of a medium, devoid of any human or animal compound and specially designed for early embryo development (from the zygote to the eight-cell stage), SMART2, in intracytoplasmic sperm injection (ICSI) and to compare it with a medium containing human serum albumin (EllioStep2). METHODS: Oocytes from 50 ICSI attempts were randomly placed, after sperm injection, into either SMART2 or EllioStep2. After a 48-hr incubation, the embryos were examined for quality scoring before transfer or freezing. RESULTS: The percentage of normally fertilized oocytes per intact oocytes was slightly higher using SMART2 (139/199 vs. 135/224, respectively, for SMART2 and EllioStep2; P < 0.05). The distribution of embryo scores and the percentage of embryos with a fair morphology (71/143 vs. 72/148, respectively, for SMART2 and EllioStep2; not significant) were identical in both media. CONCLUSIONS: These data show that SMART2 medium can be successfully used for early embryo growth and, because it is devoid of any human or animal compound, offers better safety for patients than conventional media. PMID- 9987689 TI - Fertilization, embryo quality, and cryosurvival in in vitro fertilization and intracytoplasmic sperm injection cycles. AB - PURPOSE: Our purpose was to investigate the influence of semen quality on fertilization, embryo morphology, cleavage, and cryosurvival in conventional in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) programs. METHODS: A retrospective analysis of 513 couples undergoing IVF and 255 couples undergoing ICSI was done. RESULTS: Semen quality influenced fertilization in IVF and abnormal fertilization in IVF and ICSI, but no effects on the development, morphology, implantation capacity, or cryosurvival of embryos were found. Fertilization, embryo quality, and cryosurvival rates were similar after IVF and ICSI. The fertilization rate of mature oocytes in IVF was lower when cytoplasmic immaturity in the oocyte population was frequent. The speed of development of embryos was 2 hr faster after ICSI than after IVF. Two-cell-stage embryos survived best after cryopreservation with propanediol and sucrose on day 2. CONCLUSIONS: After fertilization, semen parameters had no effect on the quality or cryosurvival of embryos in either IVF or ICSI. PMID- 9987691 TI - Differential effect of common laboratory treatments on hypoosmotic swelling responses of human spermatozoa. AB - PURPOSE: The impact of some of the common laboratory interventions on the hypoosmotic swelling (HOS) responses of human-spermatozoa was investigated. METHODS: The semen samples underwent different laboratory treatments prior to the standard HOS test, which involved incubation of sperm in the hypoosmotic solution. Fresh semen served as a control for all treatment groups and underwent the same HOS procedure. The HOS-reactive spermatozoa and the type of HOS reactions (swelling types) in each group were identified under a phase-contrast microscope for comparison. RESULTS: All the seven types of HOS responses documented in fresh semen sperm also occurred in the laboratory-processed sperm. The total HOS responses of sperm that underwent cryopreservation, heat shock, and Percoll wash were significantly different from those of the corresponding control. Percoll washing of semen influenced HOS subtypes a and g; cryopreservation affected subtypes a, b, c, and d; and heat shock altered subtypes a, f, and g. In contrast, prolonged postejaculation and cold shock did not affect any of the HOS responses. None of the treatments influenced the d and e responses. CONCLUSIONS: These results indicate that the total HOS response value and specific response subtypes are significantly affected by some of the laboratory treatments but not others. PMID- 9987690 TI - Use of failed-fertilized oocytes for diagnostic zona binding purposes after sperm binding improvement with a modified medium. AB - PURPOSE: Because the availability of prophase oocytes for zona binding testing is limited, we compared sperm binding to the zona of failed-fertilized intracytoplasmic sperm injection (ICSI) and in vitro fertilization (IVF) oocytes after incubation in a standard IVF medium and a specially composed binding improvement medium. METHODS: Semen samples from nine patients and nine fertile donors were separated in parallel by the standard swim-up method in both media. Subsequently, hemizona assays were performed with prophase, failed-fertilized ICSI and IVF oocytes. RESULTS: Sperm separation resulted in a significantly higher sperm count (P < 0.01) and progressive motility (P = 0.018) in binding improvement medium. Moreover, spermatozoa coincubated with hemizonae (prophase, failed-fertilized ICSI and IVF oocytes) in binding improvement medium bound significantly more to hemizonae than in the controls (P < 0.01). However, the hemizona index did not differ. CONCLUSIONS: Thus, the limited number of human zonae can be increased by the use of oocytes that failed to fertilize during ICSI or IVF. This will lead to a qualitative improvement of the diagnostic spectrum in male-factor infertility. PMID- 9987692 TI - Sperm creatine kinase activity in normospermic and oligozospermic Hungarian men. AB - PURPOSE: Our purpose was to measure sperm creatine phosphokinase (CK) activity, which reflects cytoplasmic retention in immature spermatozoa, in normospermic and oligozospermic Hungarian men. METHODS: A study of 109 randomly selected men in a university-based andrology laboratory was done. RESULTS: CK activity differed between normospermic and oligozospermic men (0.21 +/- 0.02 vs. 1.19 +/- 0.15 CK IU/10(8) sperm; n = 56 and n = 53; mean +/- standard error of the mean, respectively). There was an inverse correlation between sperm concentration and CK activity (r = -0.70; n = 109). However, 28% of men in the range with less than 10 million sperm/ml had normal sperm CK activity (below the mean + 2 standard deviations of the group with greater than 30 x 10(6) sperm/ml), whereas 36% of men in the group with 20-30 million sperm/ml and 5% in the group with greater than 30 million sperm/ml had elevated CK activities, indicating that the incidence of mature and immature spermatozoa in specimens is independent from the sperm concentrations. CONCLUSIONS: The improved facility of sperm CK activity measurements, compared with sperm concentrations, in the assessment of sperm maturity was confirmed in a Hungarian population. The CK measurements aid the selection of the most efficient treatment for couples with male-factor or unexplained infertility, particularly when considering the options of intrauterine insemination, varicocelectomy followed by a waiting period, or ovulation workup/induction in wives of men who are oligozospermic but may have fertile sperm. PMID- 9987693 TI - The Graafian follicle is a site of L-ascorbate accumulation. AB - PURPOSE: Our purpose was to evaluate the L-ascorbate level in human preovulatory follicular fluid and to quantify the blood/follicle gradient for vitamin C. The effect of smoking on the follicular L-ascorbate concentration was studied. The correlations were tested between follicular L-ascorbate and follicle size and oocyte maturity. METHODS: In 65 women undergoing in vitro fertilization, samples of follicular fluid and blood serum were collected. Biochemical analyses included L-ascorbate determinations by a colorimetric method and cotinine measurements by a radioimmunoassay. RESULTS: The average follicular fluid:serum ratio for L ascorbate was 1:68. Ascorbate levels in follicular fluid and serum were significantly correlated. The follicular L-ascorbate level did not correlate with the follicle size and the oocyte maturity grade. Insignificantly lowered follicular L-ascorbate levels were observed in smokers. CONCLUSIONS: The extracellular compartment of the Graafian follicle is a site of an ascorbate accumulation. Exposure to tobacco smoke does not significantly diminish the intrafollicular pool of L-ascorbate. PMID- 9987694 TI - Fluorescence in situ hybridization with chromosome paint probes: a novel approach to assess aneuploidy in human sperm nuclei. AB - PURPOSE: Fluorescence in situ hybridization (FISH) using whole-chromosome paint probes was performed to evaluate disomy and diploidy frequency for chromosomes 1, 18, 19, and 22 in human sperm nuclei. METHODS: Ten subjects of proven fertility and normal spermatic parameters were included in the study. A dual-color FISH method was carried out. RESULTS: A total of 157,896 spermatozoa was scored. The mean frequencies of disomic sperm for chromosomes 1, 18, 19, and 22 were 0.22% (range, 0.19 to 0.28%), 0.24% (range, 0.14 to 0.37%), 0.22% (range, 0.17 to 0.30%), and 0.25% (range, 0.21 to 0.29%), respectively. The mean frequency of diploidy was 0.14% (range, 0.09 to 0.18%). No interindividual and interchromosomal variations in the aneuploidy frequency were observed between the different subjects. CONCLUSIONS: FISH with whole-chromosome paint probes provides a novel and efficient approach for disomy assessment in human sperm nuclei. PMID- 9987695 TI - Trophoblast persists despite lack of sex-steroid support following ovum donation. PMID- 9987696 TI - Alpha-adrenergic blocking drugs in clinical medicine. AB - The alpha-adrenergic blockers have played an important role in the treatment of vascular diseases. Nonselective alpha blockers have been used as treatments for patients with severe hypertension, including pheochromocytoma. Selective alpha 1 blockers have been used in the treatment of hypertension and prostatic obstruction, and these drugs have also been considered in the treatment of other vascular and nonvascular conditions. They have unique metabolic actions, specifically on plasma lipids and lipoproteins, which could be of clinical benefit. PMID- 9987697 TI - The pharmacodynamics of sumatriptan in nitroglycerin-induced headache. AB - Migraine is a common disorder that causes significant morbidity in those afflicted. Many novel antimigraine compounds are in clinical development, yet full characterization of each one's pharmacodynamic behavior is a formidable task due to the difficulty in studying a migraineur during an attack. Nitroglycerin (NTG) administration commonly causes a headache with some features similar to those of a migraine. As such, NTG has been used as a model of vascular headaches, including migraine. The pharmacodynamic effects of nitroglycerin and sumatriptan on middle cerebral artery blood flow velocity (MCAv) and headache scores were studied in 10 healthy male volunteers. An intravenous infusion of NTG titrated to 0.5 mcg/kg/min over 30 minutes resulted in a median reduction from baseline in MCAv of 27% (range: 16.4%-37.3%). Nine of the subjects developed a headache with a median verbal score of 3.5 of 10 (range: 0-5). Subjects received sumatriptan either 2 mg intravenously or 6 mg subcutaneously, which abated clinical headache in 9 of the 10 subjects (p = 0.030). A median sumatriptan-induced increase in MCAv of 21% (p = 0.054) suggested a constricting effect on the NTG-induced dilated MCA. A two-compartment pharmacokinetic/indirect-effects pharmacodynamic model was fit to the sumatriptan concentration and MCAv data using iterative two stage analysis. This model was unbiased and fit the concentration (r2 = 0.98) and the MCAv (r2 = 0.79) data well. These results suggest that NTG-induced headache and the development of pharmacokinetic/pharmacodynamic models could serve as a useful method for exploring the mechanisms of abortive migraine drugs. PMID- 9987698 TI - A double-blind, placebo-controlled, ascending-dose evaluation of the pharmacokinetics and tolerability of modafinil tablets in healthy male volunteers. AB - A randomized, double-blind, placebo-controlled, ascending-dose study was conducted to evaluate the pharmacokinetic and safety profiles of increasing modafinil doses (200 mg, 400 mg, 600 mg, 800 mg) administered orally over a 7-day period in normal healthy male volunteers. Eight subjects (six modafinil; two placebo) were randomized to each of the four dose groups. Modafinil or a placebo was administered once daily for 7 days. Serial blood samples were obtained following administration of the day 1 and day 7 doses for characterization of pharmacokinetics, and trough samples were obtained prior to dosing on days 2 through 6 to assess the time to reach the steady state. Pharmacokinetic parameters were calculated using noncompartmental methods. Modafinil steady state was reached after three daily doses. Modafinil pharmacokinetics were dose and time independent over the range of 200 mg to 800 mg. Steady-state pharmacokinetics of modafinil were characterized by a rapid oral absorption rate, a low plasma clearance of approximately 50 mL/min, a volume of distribution of approximately 0.8 L/kg, and a long half-life of approximately 15 hr. Modafinil was primarily eliminated by metabolism. Modafinil acid was the major urinary metabolite. Stereospecific pharmacokinetics of modafinil were demonstrated. The d modafinil enantiomer was eliminated at a threefold faster rate than 1-modafinil. Modafinil 200 mg, 400 mg, and 600 mg doses were generally well tolerated. The modafinil 800 mg dose panel was discontinued after 3 days of treatment due to the observation of increased blood pressure and pulse rate. The safety data from this study suggest that the maximum tolerable single daily oral modafinil dose, without titration, may be 600 mg. PMID- 9987699 TI - Long-term systemic exposure of orlistat, a lipase inhibitor, and its metabolites in obese patients. AB - Orlistat, a lipase inhibitor, acts locally in the gastrointestinal tract; its systemic exposure is not required for its efficacy. However, knowledge of the extent of its systemic exposure is important for its safe use in obese patients, the intended target population. Pharmacokinetic screening in obese patients was carried out by monitoring plasma concentrations of unchanged orlistat and its metabolites in five key double-blind, placebo-controlled phase II/III studies. Results of these studies involving the monitoring of plasma samples indicate that detection of intact orlistat in plasma was sporadic, and measurable concentrations were low (< 10 ng/mL or 0.02 microM) without evidence of accumulation, which is consistent with minimal absorption. It is concluded that systemic exposure of orlistat is negligible; at a clinically efficacious dose level, orlistat is unlikely to produce systemic lipase inhibition. PMID- 9987700 TI - Pharmacokinetics and tolerability of intravenous trecovirsen (GEM 91), an antisense phosphorothioate oligonucleotide, in HIV-positive subjects. AB - Trecovirsen, a 25-mer antisense phosphorothioate oligonucleotide targeted at the gag site of the HIV gene, was administered to HIV-positive volunteers as an i.v. infusion. Single doses ranged from 0.1 to 2.5 mg/kg in an ascending escalation in cohorts of 6 to 12 subjects. Plasma trecovirsen concentrations and pharmacokinetic parameters could be assessed at doses > or = 0.3 mg/kg. Peak plasma concentrations and AUC values increased disproportionately with increasing dose while elimination half-life increased and plasma clearance decreased, indicating a saturable process over this dose range. The only significant adverse event observed was an isolated, transitory increase in activated partial thromboplastin time at doses > or = 2.0 mg/kg that was related to plasma trecovirsen concentrations and is attributed to the polyanionic character of the molecule. Thus, trecovirsen administration was well tolerated in single i.v. doses up to 2.5 mg/kg. PMID- 9987701 TI - Carbamazepine levels in head hair of patients under long-term treatment: a method to evaluate the history of drug use. AB - Carbamazepine (CBZ) concentrations were determined in the sections of head hair from 40 patients (22 males and 18 females), ages 5 to 81, who were receiving this drug systemically. Hair treatment included dissolution, liquid phase extraction procedures, and immunoassay (Abbott TDx) or high-pressure liquid chromatography (HPLC) analytical techniques. The mean values of CBZ levels in the hair from the 1st section (close to hair root) to the 5th section for female patients were 26.82, 19.18, 17.28, 15.09, and 14.62 micrograms/g according to HPLC measurements. Immunoassay gave generally slightly higher results. The mean values of CBZ in the hair sections according to the immunoassay technique were 30.53, 21.90, 19.83, 17.45, and 16.99 micrograms/g, respectively, from the 1st to the 5th sections. The corresponding mean values for male patients by HPLC and immunoassay techniques were 21.97, 17.30, 15.03, 13.02, and 11.21 micrograms/g and 25.98, 20.52, 17.15, 14.87, and 12.31 micrograms/g. Generally, a reduction of drug concentrations in hair from the first to the subsequent segments was observed. Higher amounts of CBZ were deposited in black, untreated hair (e.g., not dyed or permed). CBZ concentrations in hair sections were found to be dependent on the dosage (r = 0.979, p < or = 0.001) but not on the gender. The data indicate the possible use of hair section testing as a marker of the dosage history and the compliance of patients under long-term treatment with CBZ. PMID- 9987702 TI - The effects of acetaminophen on pharmacokinetics and pharmacodynamics of warfarin. AB - The oral anticoagulant warfarin is clinically administered as a racemic mixture of two enantiomers, (R) and (S). Many relevant drug interactions with warfarin have been attributed to the specific metabolic inhibition of the elimination of the more pharmacologically active (S)-enantiomer. To investigate reports that acetaminophen can potentiate the anticoagulant effect of warfarin, 20 healthy male volunteers were each given single oral 20 mg doses of racemic warfarin on three separate occasions: (1) alone, (2) after 1 day of acetaminophen (4 g/d), and (3) after 2 weeks of acetaminophen (4 g/d). The urinary excretion pattern of acetaminophen and its metabolites was not significantly altered over its course of administration. The (R)- and (S)-enantiomers of warfarin exhibited significantly different pharmacokinetic properties. However, acetaminophen did not alter the disposition of either (R)- or (S)-warfarin. All subjects exhibited a pharmacodynamic response to racemic warfarin. The response was not significantly altered in the presence of acute or chronic acetaminophen dosing, as assessed by prothrombin time and factor VII concentrations. PMID- 9987703 TI - Lack of effect of erythromycin and ketoconazole on the pharmacokinetics and pharmacodynamics of steady-state intranasal levocabastine. AB - The single-dose effects of the cytochrome P-450 inhibitors erythromycin and ketoconazole on the steady-state pharmacokinetics and electrocardiographic repolarization pharmacodynamics of intranasal levocabastine, a potent and selective H1-receptor antagonist, were evaluated in healthy young male subjects. Two randomized, open-label, placebo-controlled, two-way crossover studies were performed. Levocabastine nasal spray was administered as two sprays per nostril (0.05 mg/spray) twice daily (for a total daily dose of 0.4 mg) for 6 days. On Day 7, a single dose of 0.2 mg was administered followed immediately by a single dose of either oral placebo, erythromycin 333 mg, or ketoconazole 200 mg. In all treatment groups, levocabastine was rapidly absorbed, with peak plasma concentrations reached at approximately 3 hours in the erythromycin study and 2.8 hours in the ketoconazole study. The mean terminal half-life was approximately 45 and 44 hours, respectively. In both studies, mean steady-state plasma concentrations and pharmacokinetics of levocabastine following the single doses of erythromycin or ketoconazole were not significantly different from corresponding values seen with the concomitant administration of the placebo. No clinically significant mean changes from baseline in QT or QTc (QT corrected for heart rate) intervals occurred in any of the treatment groups, and none of the subjects in either study experienced abnormally prolonged QTc intervals. Intranasal levocabastine was well tolerated, with no difference in the incidence of adverse events between treatment groups in either study; adverse events were generally mild in severity. Since levocabastine undergoes only minimal hepatic metabolism and is not a substrate for or an inhibitor of cytochrome P-450, the likelihood of systemic drug interactions with drugs affecting the cytochrome P 450 system is minimal. PMID- 9987704 TI - The effect of converting from pravastatin to simvastatin on the pharmacodynamics of warfarin. AB - Forty-six adult patients maintained on warfarin therapy were converted from pravastatin to simvastatin. Mean international normalized ratio (INR) significantly increased from 2.42 to 2.74, p = 0.002. Although warfarin doses were reduced in 7 patients and increased in 4 patients following the post conversion INR measurements, the pre- and postconversion median weekly warfarin dose of all 46 patients did not differ significantly. The number of patients with an INR > 3.0 increased significantly from 6 to 16 following the conversion. There was no report of unusual episodes of bleeding. The results indicate that antihyperlipidemic therapy can be changed safely from pravastatin to simvastatin in patients who are taking warfarin concomitantly. Additional anticoagulation monitoring is not necessary in institutions where patients are followed in formal anticoagulation clinics. PMID- 9987706 TI - A clozapine overdose with markedly elevated serum levels. AB - Clozapine (Clozaril) is an atypical antipsychotic agent used to treat schizophrenia refractory to other pharmacological agents. This report describes an accidental clozapine overdose. The half-life of clozapine in this patient was determined from two blood levels, one obtained on admission and the second 10.5 hours later. The calculated half-life of 8.11 hours is consistent with published levels for single doses and suggests an apparent stability in clozapine elimination half-life in the face of overdose. The maximum clozapine blood level attained was probably among the highest nonfatal levels reported. The patient recovered fully following hospital admission for monitoring and supportive care. This case report illustrates the usefulness of following the time course of the changes in blood level at selected time intervals, as well as the importance of entertaining a diagnosis of drug overdose in patients presenting with acute mental status changes. PMID- 9987705 TI - Effects of rifampin on tacrolimus pharmacokinetics in healthy volunteers. AB - Tacrolimus is a marketed immunosuppressant used in liver and kidney transplantation. It is subject to extensive metabolism by CYP3A4 and is a substrate for P-glycoprotein-mediated transport. A pharmacokinetic interaction with rifampin, an antituberculosis agent and potent inducer of CYP3A4 and P glycoprotein, and tacrolimus was evaluated in six healthy male volunteers. Tacrolimus was administered at doses of 0.1 mg/kg orally and 0.025 mg/kg/4 hours intravenously. The pharmacokinetics of tacrolimus were obtained from serial blood samples collected over 96 hours, after single oral and intravenous administration prior to and during an 18-day concomitant rifampin dosing phase. Coadministration of rifampin significantly increased tacrolimus clearance (36.0 +/- 8.1 ml/hr/kg vs. 52.8 +/- 9.6 ml/hr/kg; p = 0.03) and decreased tacrolimus bioavailability (14.4% +/- 5.7% vs. 7.0% +/- 2.7%; p = 0.03). Rifampin appears to induce both intestinal and hepatic metabolism of tacrolimus, most likely through induction of CYP3A and P-glycoprotein in the liver and small bowel. PMID- 9987707 TI - Early diagnosis of dementia. PMID- 9987708 TI - Early diagnosis of dementia: neuropsychology. AB - Neuropsychology contributes greatly to the diagnosis of dementia. Cognitive deficits can be detected several years before the clinical diagnosis of dementia. The neuropsychological profile may indicate the underlying neuropathology. Neuropsychological assessment at an early stage of dementia has two goals: (a) to determine a memory disorder, not always associated with a memory complaint, and (b) to characterize the memory disorder in light of the cognitive neuropsychology and to assess other cognitive (and noncognitive) functions toward integrating the memory disorder in a syndrome. We review the global tools, the memory tests that describe the memory profile and indicate the underlying pathology, the assessment of other cognitive functions, and the neuropsychological patterns of typical Alzheimer's disease, frontotemporal dementia, primary progressive aphasia, semantic dementia, Lewy body dementia, subcortical dementia, and vascular dementia. These patterns must be interpreted in the light of the history, rate of progression, imaging results, and nature of existing behavioral disturbances. Moreover, there may be overlap between two or more pathologies, which complicates the diagnostic process. Follow-up of patients is necessary to improve diagnostic accuracy. PMID- 9987709 TI - Early diagnosis of dementia: neuroimaging. AB - The use of neuroimaging is reviewed in the diagnosis of dementia, especially Alzheimer's disease (AD). Computed tomography (CT) may be used to exclude other causes of dementia than AD. The finding of cortical or subcortical atrophy on CT or magnetic resonance imaging (MRI) itself does not indicate AD. Hippocampal atrophy on CT/MRI provides a useful early marker, although further longitudinal and neuropathological study is required. CT- and MRI-based measurements of hippocampal atrophy show promise in providing useful diagnostic information for discriminating patients with probable AD from normal elderly individuals. Using a standardized imaging protocol, including some assessment of hippocampal atrophy, can save costs since patients with suspected AD must undergo a cross-sectional imaging study to exclude other (treatable) causes of dementia. Combining an assessment of hippocampal atrophy with cerebral blood flow measurements by single photon emission computed tomography is not warranted either from a clinical or from an economic point of view. PMID- 9987710 TI - Impairment of callosal and corticospinal system function in adolescents with early-treated phenylketonuria: a transcranial magnetic stimulation study. AB - The transcranial activation and the conduction properties of corticospinal and callosal neurons were investigated in 12 early-treated adolescents (aged 17.3, SD 3.5 years; range 14-27 years) with phenylketonuria (PKU) by focal transcranial magnetic stimulation (fTMS) of the motor cortex. The patients had no functionally relevant motor disturbances in daily life or on clinical testing. Corticospinally mediated excitatory (response thresholds, amplitudes, central motor latencies) and inhibitory [duration of postexcitatory inhibition (PI)] effects of fTMS were investigated in contralateral hand muscles. Transcallosal inhibition (TI) (onset latency, duration, transcallosal latency) of tonic electromyographic (EMG) activity was tested in ipsilateral muscles. Peripheral motor latencies were determined for responses elicited by magnetic stimulation over cervical nerve roots. Ten normal subjects served as controls. Since in all PKU patients, central and peripheral motor latencies were normal, no neurophysiological indication of a demyelination of corticospinal or peripheral motor fibres was found. However, cortical thresholds of corticospinally mediated responses were increased (52.1, SD 11.6% versus 35.0, SD 7.4% of maximum stimulator output; P < 0.05; n = 24 hands) and their amplitudes reduced (2.9, SD 1.4 mV versus 6.1, SD 1.5 mV, P < 0.05). The duration of PI was shortened (132, SD 53 ms versus 178, SD 57 ms; P < 0.05). TI was absent in 37.5% of the investigated hands or tended to be weak. When TI was present, its onset latencies (38.0, SD 3.6 ms versus 34.7, SD 3.3 ms) and transcallosal latencies were prolonged (18.5, SD 3.8 ms versus 14.8, SD 3.2 ms), while its duration was normal. These abnormal excitatory and inhibitory effects of fTMS suggest a reduced susceptibility of cortical excitatory and inhibitory neuronal structures compatible with a loss of neurons or a rarefication of their dendrites. PMID- 9987711 TI - Chemotherapy is effective as early treatment for primary central nervous system lymphoma. AB - Primary central nervous system lymphoma (PCNSL) is a lymphoma arising within the brain or spinal cord in the absence of evident localisation outside the central nervous system (CNS). Poor results in the management of relapsed PCNSL justify the need for vigorous initial therapeutic regimens, and chemotherapy should not be reserved for recurrent disease. Chemotherapy (MBACOD scheme) was delivered prior to irradiation in a group of 20 PCNSL patients, another 8 PCNSL patients underwent radiotherapy only, and the overall survival was evaluated. Computed tomography (CT) images in the group of patients treated with chemotherapy, showed there to be 70% complete responders (CR), 15% non-responders (NR) and 15% partial responders (PR). Half of the CR were scheduled for radiotherapy only at tumour recurrence. The median disease-free period and survival time of the whole group treated with early chemotherapy followed by radiotherapy were 24 and 32 months, respectively, but in the subgroup of CR (70%), taking into account also the patients not yet receiving radiotherapy, these were 38 and 48 months, respectively. The disease-free and survival times in the group of CR (75%) of patients treated with radiotherapy only were 13 and 18 months, respectively. At tumour recurrence, CR to chemotherapy had a second disease-free period longer than 2 years after radiotherapy. Our data support the belief that in scheduling the treatment of PCNSL after histological diagnosis, the first step is to devise high-dose chemotherapy with drugs able to cross an intact blood-brain barrier. The results of our primary approach with early chemotherapy in PCNSL support a consensus to continue chemotherapy until tumour recurrence, and only at that event to initiate radiotherapy. It is a challenge and an option worthy of continuing investigation. PMID- 9987712 TI - Specificity of omega-conotoxin MVIIC-binding and -blocking calcium channel antibodies in Lambert-Eaton myasthenic syndrome. AB - An immunoprecipitation assay was used to measure omega-conotoxin MVIIC (P/Q-type) binding and blocking calcium channel antibodies in 67 patients with Lambert-Eaton myasthenic syndrome (LEMS) and in a large control population. We first showed the presence of omega-conotoxin MVIIC-blocking antibody in LEMS patients. Binding antibodies were detected in 55 of 67 (82.1%) LEMS patients and in 2 of 296 (0.7%) controls. In contrast, blocking antibodies were positive in 14 of 67 (20.9%) LEMS patients and 8 of 171 (4.7%) controls. No LEMS patient had negative binding antibodies and positive blocking antibodies. The immunoprecipitation assay detected no antibodies against the whole P/Q-type calcium channel in either the paraneoplastic cerebellar degeneration or the amyotrophic lateral sclerosis sera. Neither the omega-conotoxin MVIIC-binding nor the -blocking calcium channel antibodies were correlated with clinical severity across the individuals, but longitudinal studies of some LEMS patients showed an inverse relation between binding antibody titre and disease severity. We concluded that the 125I-omega conotoxin MVIIC assay for anti-P/Q-type voltage-gated calcium channel antibodies is highly specific for LEMS and that this sensitive binding antibody assay could be more valuable than the blocking antibody assay in the diagnosis of LEMS. PMID- 9987713 TI - Variable number tandem repeat dopamine transporter gene polymorphism and Parkinson's disease: no association found. AB - We studied a variable number of tandem repeat polymorphisms in the dopamine transporter gene in search of an association with Parkinson's disease in a French population. Five alleles were detected, consisting of 7, 8, 9, 10 and 11 copies of the 40-base pair repeat sequence, of which the 10-copy allele was the most common. There was no significant difference between the patients and the control subjects in the distribution frequencies of the alleles or genotypes, or in ages at onset in patients between the main allelic classes. PMID- 9987714 TI - High incidence of a survival motor neuron gene/cBCD541 gene ratio of 2 in Japanese parents of spinal muscular atrophy patients: a characteristic background of spinal muscular atrophy in Japan? AB - Most spinal muscular atrophy (SMA) patients lack the survival motor neuron gene (SMN). However, the patients retain at least one copy of the cBCD541 gene (BCD), which is highly homologous with SMN. Here, we determined the SMN/BCD copy number ratios (the S/B ratios) of 12 parents of Japanese SMA patients with a homozygous SMN deletion, using competitive oligonucleotide priming polymerase chain reaction. We identified an S/B ratio of 2 in 25% of the parents examined, whereas less than 2% of parents of SMA patients in Western populations have an S/B ratio of 2. The high incidence of an S/B ratio of 2 in Japanese parents of SMA patients may reflect the characteristic genetic background of SMA in Japan. PMID- 9987715 TI - Precipitating factors of transient global amnesia. PMID- 9987716 TI - Macular preservation with bilateral visual field defect caused by embolic occlusion of the posterior cerebral arteries. PMID- 9987717 TI - Increased coagulatory activity in subcortical arteriosclerotic encephalopathy (Binswanger's disease) PMID- 9987718 TI - No transneuronal degeneration between human cortical motor neurons and spinal motor neurons. PMID- 9987720 TI - Repeatability and validity of astigmatism measurements. AB - BACKGROUND: As more patients inquire about refractive surgical procedures, the measurement of astigmatism prior to surgery becomes more important in assessing refractive outcome. Knowledge of the repeatability of the astigmatism measurement allows one to distinguish a true change in cylinder power from measurement error. METHODS: Forty adults with structurally normal eyes and refractive errors were evaluated for the repeatability of astigmatic refractive error measures. Noncycloplegic and cycloplegic measurements of refractive astigmatism were made by retinoscopy, subjective refraction, and autorefraction. All measures were made at 2 visits within 2 weeks by the same examiner. Difference versus mean plots and the 95% limits of agreement of each technique determined the repeatability of a measurement and the agreement between the methods of measurement. RESULTS: The most reliable measure of astigmatic refractive error was cycloplegic autorefraction, with 95% limits of agreement of +/- 0.28 D, followed by noncycloplegic autorefraction (+/- 0.35 D) and cycloplegic subjective refraction (+/- 0.44 D). Noncycloplegic retinoscopy was the least reliable astigmatic refractive error measure, with interoccasion 95% limits of agreement of +/- 1.02 D. The most repeatable measurement of cylinder axis was cycloplegic autorefraction; none of the measurements differed by 10 degrees or more. The least repeatable measurement was noncycloplegic retinoscopy; 40% of the measurements differed by 10 degrees or more. CONCLUSION: For studies seeking to measure changes in astigmatism in normal eyes, cycloplegic autorefraction is the method of choice. PMID- 9987721 TI - Videokeratography, keratometry, and refraction after penetrating keratoplasty. AB - PURPOSE: To identify the correlation between videokeratography, autorefractometry, autokeratometry, and keratometry measurements and the subjective manifest refraction and spectacle-corrected visual acuity after penetrating keratoplasty. METHODS: We studied 100 eyes from 100 patients that had undergone penetrating keratoplasty. All eyes were examined by videokeratography (EyeSys 2000) (axial, tangential, and refractive power maps), autorefractometry, autokeratometry, and keratometry. Measurements were made at an an average of 19 +/- 9 months after surgery. Postoperative refractive astigmatism, spherical equivalent refraction, and spectacle-corrected visual acuity were studied by regression analysis. RESULTS: Both the total topographic cylinder measured by the refractive power map and topographic cylinder measured by the axial power map showed the strongest correlation with the manifest refractive cylinder (rs = +0.89, P < .001). The axis of astigmatism determined by keratometry and autokeratometry showed the strongest correlation with the subjective manifest refraction axis (rs = +0.87, P < .001). The total topographic cylinder showed the strongest correlation with the spectacle-corrected visual acuity (rs = +0.38, P = .001); however the topographic indices of predicted corneal acuity, corneal acuity, corneal uniformity index, asphericity, and refractive power symmetry did not correlate with spectacle-corrected visual acuity. CONCLUSION: Measurement of astigmatism after penetrating keratoplasty can be made more accurate by using videokeratographic measurements to supplement retinoscopic and manifest refraction. Other useful methods for predicting the axis of refractive astigmatism include keratometry, autokeratometry, and autorefractometry. In this study, indices designed to measure corneal surface irregularity failed to predict visual acuity after penetrating keratoplasty. PMID- 9987719 TI - Treatment of hyperopia with contact Ho:YAG laser thermal keratoplasty. AB - PURPOSE: To evaluate the effectiveness, safety, and stability of contact Ho:YAG laser thermal keratoplasty for low to moderate hyperopia. METHODS: Fifty-five hyperopic eyes of 39 patients were treated with a Technomed contact Ho:YAG laser; 23 eyes were treated a second time. Treatment parameters were 1 octagonal ring of 8 spots with a treatment diameter of 6 mm, 7 mm, or 8 mm. Efficacy of the Ho:YAG laser treatment was evaluated after 6 months, comparing 3 treatment zone diameters. Stability and efficacy after 12 months was evaluated comparing 7-mm and 8-mm treatment zone diameters. RESULTS: Mean reduction of spherical equivalent refraction after 6 months was not statistically significantly different between the 6-mm or 7-mm diameter zones: 1.42 (+/- 1.30) D versus 2.22 (+/- 0.44) D. An 8-mm diameter treatment zone was significantly less effective, 1.12 (+/- 0.47) D. Longer follow-up did not show stability: mean reduction of spherical equivalent manifest refraction was 1.58 (+/- 0.45) D for the 7-mm diameter treatment zone and 0.82 (+/- 0.61) D for the 8-mm diameter treatment zone after approximately 12 months. Retreatment had a limited additive effect. No clinically significant loss of spectacle-corrected visual acuity was reported. No eyes lost more than 1 line of visual acuity. CONCLUSION: Contact Ho:YAG laser thermal keratoplasty corrected hyperopia up to 2.50 D, but predictability was poor and a regression of initial effect occurred. Instability of refraction persisted to 1 year after surgery. PMID- 9987723 TI - Changes in corneal topography after laser in situ keratomileusis for myopia. AB - OBJECTIVE: To define qualitative patterns of corneal topography after excimer laser in situ keratomileusis (LASIK) and to assess whether epithelial hyperplasia occurred after LASIK. METHODS: A consecutive series of 18 myopic eyes of 10 patients having refractive surgery in an academic practice at the Royal Victorian Eye and Ear Hospital, Melbourne, Australia was followed prospectively after LASIK. Four eyes were treated with the VISX 20/20 excimer laser and 14 eyes were treated with the Nidek EC5000 excimer laser. Videokeratography was performed on each eye at 1, 3, and 6 months after surgery. The common digital subtraction topographic patterns were classified and used to speculate whether epithelial hyperplasia occurred. RESULTS: After LASIK, 83% of subtraction maps at 1 month and 81% at both 3 and 6 months showed steepening in the ablation zone. There was no clear correlation between the topographic maps and spectacle-corrected visual acuity or regression of the initial effect after surgery. CONCLUSION: Corneal topographic changes similar to those seen after photorefractive keratectomy (PRK) occur after LASIK for myopia. PMID- 9987722 TI - Loss and recovery of corneal sensitivity following photorefractive keratectomy for myopia. AB - BACKGROUND: Photorefractive keratectomy affects corneal innervation in a new, and drastic, way. This inevitably results in a significant loss of corneal sensitivity. This paper investigates the pattern of sensitivity loss and recovery following PRK for low to moderate myopia. METHODS: Patients were recruited for two separate studies. Longitudinal Study: 10 patients, treated with a -6.00 D/6 mm PRK ablation, were examined over a 1-year period. Transverse Study: A comparison was made between 35 non-contact lens wearers, 80 contact lens wearers, and 60 patients who underwent five different PRK treatments, 1 year previously. Corneal sensitivity was assessed using the Non-Contact Corneal Aesthesiometer at four corneal locations: centrally, temporally, medially, inferiorly, on all patients. RESULTS: Longitudinal Study: Corneal sensitivity was significantly reduced at week 1, with a further significant reduction at week 2. A gradual recovery in sensitivity then followed to reach preoperative levels by 1 year. Transverse Study: There was no significant difference in corneal sensitivity found as a result of different PRK ablation depths. The depth of ablation was not a factor in corneal sensitivity recovery in low to moderate myopic corrections. Corneal sensitivity in the PRK treated eyes was significantly lower than in the control groups. CONCLUSION: The immediate loss of corneal sensitivity after surgery was due to the total removal of the corneal epithelial nerve supply and a substantial portion of the underlying stromal nerves. The further decrease at week 2 was probably due to the new epithelium acting as barrier to stimulation. The gradual recovery of corneal sensitivity was most likely caused by epithelial reinnervation within the ablation zone, but this was still below normal levels at 1 year after surgery. Corneal nerve function demonstrates a biphasic pattern of loss and recovery following the excimer laser correction of low to moderate myopia. PMID- 9987724 TI - Refractive keratotomy after photorefractive keratectomy. AB - BACKGROUND: The current surgical procedures available for the treatment of residual myopia and/or astigmatism after photorefractive keratectomy (PRK) include refractive keratotomy, laser in situ keratomileusis (LASIK), repeat PRK, or photorefractive astigmatic keratectomy (PARK). In this study, we investigate the safety and efficacy of refractive keratotomy for the correction of residual myopia and/or astigmatism after PRK. METHODS: Ten eyes of 9 patients underwent refractive keratotomy after excimer laser photorefractive keratectomy using the Lindstrom nomogram. PRK procedures were performed using the VISX 20/20 system by one surgeon. RESULTS: All eyes except one obtained an uncorrected visual acuity of 20/40 or better. One eye developed significant haze following PRK with myopic astigmatic regression and underwent refractive keratotomy to correct the residual refractive error. This patient was also the only patient who lost 2 lines of spectacle-corrected visual acuity secondary to corneal haze. CONCLUSION: This study demonstrates that refractive keratotomy can reduce residual astigmatism and myopia that may be present following excimer laser photorefractive keratectomy. Our results suggest there is no need to change the refractive keratotomy nomograms for eyes that have previously undergone PRK. PMID- 9987725 TI - Combined laser in situ keratomileusis and photorefractive keratectomy for extreme myopia. AB - BACKGROUND: Current refractive surgical techniques, specifically photorefractive keratectomy (PRK) and laser in situ keratomileusis (LASIK) for the correction of extreme myopia (more than -20.00 diopters) are unpredictable and undercorrections occur frequently. A combination of both techniques, used simultaneously or separately, expands their individual range, and allows correction of higher amounts of myopia. METHODS: Both eyes of a 24-year old female patient who had a spherical equivalent refraction of -37.00 -2.00 x 170 degrees in her right eye and -38.00 -2.00 x 180 degrees in her left eye underwent LASIK and PRK (transepithelial) at the same sitting, using the Chiron automated corneal shaper and the Chiron Technolas Keracor 116 excimer laser. RESULTS: One month postoperatively, she had an uncorrected visual acuity of 20/100 in her right eye with a spherical equivalent refraction of +3.00 sphere and 20/200 in her left eye. One year after surgery she had an uncorrected visual acuity of 20/70 and a spherical equivalent refraction of +1.00 -1.00 x 30 degrees in her right eye and in her left eye 20/80 with a refraction of +1.25 sphere. CONCLUSION: LASIK and PRK combined in a simultaneous procedure are an alternative for the surgical management of extreme myopia. PMID- 9987726 TI - Sterile peripheral keratitis following laser in situ keratomileusis. AB - BACKGROUND: Sterile infiltrates have been reported as a possible complication following photorefractive keratectomy (PRK). They have not been reported following laser in situ keratomileusis (LASIK). We review a case of fleeting, sterile peripheral corneal infiltrates following LASIK. METHODS: A 53 year old patient developed peripheral, sterile corneal infiltrates along the edge of the primary flap following LASIK. This was successfully managed with topical antibiotics and corticosteroids without permanent sequelae. RESULTS: Sterile peripheral corneal infiltrates are now a known complication following LASIK. Pathogenesis is undetermined but may involve activation of marginal keratitis reminiscent of that following blepharitis or a mechanism similar to acute subepithelial infiltrative keratitis following PRK. CONCLUSION: Fleeting, sterile peripheral corneal infiltrates can occur following LASIK. This undesired complication is poorly characterized but can be successfully managed with culturing of the infiltrates, topical corticosteroids, and antibiotics. PMID- 9987727 TI - Ruptured globe 10 years after radial keratotomy. AB - PURPOSE: To report 3 cases (3 eyes) of globe rupture following blunt trauma 10 to 13 years after radial keratotomy. METHODS: Cases of traumatic ruptured globe after radial keratotomy were reviewed from a tertiary eye care center. One eye underwent therapeutic penetrating keratoplasty, the second was treated with a bandage contact lens, and the third developed retinal detachment leading to phthisis bulbi. RESULTS: Ruptured globes occurred through the keratotomy incision during activities of daily living (1 eye), assault (1 eye), and sports (1 eye). Two eyes regained a visual acuity of 20/30 or better; 1 eye was lost. CONCLUSION: Traumatic rupture of the cornea can occur more than 10 years after radial keratotomy. PMID- 9987728 TI - Centered vs. inferior off-center ablation to correct hyperopia and presbyopia. AB - BACKGROUND: We describe a new technique of inferior off-center ablation with laser in situ keratomileusis (LASIK) to correct both hyperopia and presbyopia. METHODS: This prospective clinical study was based on the empirical results obtained with LASIK in 16 hyperopic eyes of 8 patients. All patients had a centered ablation in one eye and an inferior decentered ablation in the other eye. A Schwind excimer laser was used and a planned inferior off-center ablation of 1 mm was performed. Maximum follow-up was 22 months (8 eyes). RESULTS: Patients with hyperopia that underwent inferior decentered ablation were able to read for a prolonged period of time, compared with eyes that had conventional centered excimer laser ablation. Patients with steepened corneas in the inferior and eccentric zone ended up not only with better distance but also better near vision. No loss of spectacle-corrected visual acuity in any eye has been observed to date. CONCLUSION: Planned inferior off-center ablation to correct hyperopia and presbyopia achieved better distance and near visual acuity than centered ablation. As with centered ablation, no significant regression of effect occurred with off-center ablation; reading near vision was better and more stable with inferior off-center ablation. PMID- 9987729 TI - Clear lens extraction in the 19th century--an early demonstration of premature dissemination. AB - Clear lens extraction for correction of high myopia is a concept known since at least 1800, but was performed only occasionally because of the hazards of cataract operation in general in the era before aseptic surgery. After the invention of sterilization, in 1889 a rush for myopia correction by clear lens extraction was started by Fukala in Austria/Germany and Vacher in France. It took 10 years until a retrospective comparison of operated and non-operated eyes revealed the high complication rate after clear lens extraction. After 1900, the "myopia operation" was increasingly abandoned and eventually disappeared. PMID- 9987730 TI - Topography following keratoplasty in cats is not representative of that in humans. PMID- 9987731 TI - Enhancing advanced surgical laparoscopy. Combined, routine use of microlaparoscopes and macrolaparoscopes. AB - OBJECTIVE: To describe a variety of techniques for using the microlaparoscope in conjunction with a standard-sized laparoscope for simplifying and enhancing advanced laparoscopic surgery. STUDY DESIGN: Descriptive study of microlaparoscopic techniques for enhancing macrolaparoscopic procedures. RESULTS: The microlaparoscope facilitates macrolaparoscopy by permitting: (1) specimen removal and use of 10-mm instruments without secondary, large ports; (2) performance of laparoscopic vaginal hysterectomy with the endoscopic stapler using only one 12-mm port; (3) lysis of difficult pelvic and periumbilical adhesions; (4) enhancement of visual access to difficult operative sites; (5) closure of large umbilical and secondary port sites under direct monitoring; (6) visualization from the left upper quadrant when umbilical adhesions are suspected; and (7) use as the initial entry laparoscope when extensive surgery is not anticipated. CONCLUSION: The routine, combined use of the microlaparoscope and 10-mm laparoscope significantly expands the capabilities of the advanced laparoscopic surgeon. Procedures are simplified, facilitated and made less invasive. PMID- 9987732 TI - Impact of genetic counseling on primary and preventive care in obstetrics and gynecology. AB - OBJECTIVE: To evaluate the utility of the prenatal three-generation pedigree in assessment of the obstetric patient's primary medical risks. STUDY DESIGN: In a case series, 250 charts of patients referred for amniocentesis on the basis of advanced maternal age were reviewed for a significant genetic risk of a primary care disorder. RESULTS: A total of 40 patients (16%) were at significantly increased risk for a primary care disorder. Thirty-eight patients (15.2%) were at increased risk for medical conditions for which early screening, detection and/or intervention are established. CONCLUSION: For the advanced maternal age population, formal genetic risk assessment performed prior to amniocentesis can be beneficial in primary care risk assessment. PMID- 9987733 TI - Results of AutoPap system-assisted and manual cytologic screening. A comparison. AB - OBJECTIVE: To determine the effectiveness of AutoPap QC System rescreening of all qualified negative cervical cytologic smears with selection of approximately 10% for cytotechnologist rescreening as compared to a random selection of 10% of negative cases. STUDY DESIGN: The study included 1,141,913 consecutive smears. In February 1997 an AutoPap-based QC program was implemented to select a population for rescreening. Negative cases were studied prospectively by the AutoPap QC System. Detection rates by diagnostic classification of false negative cases were compared to rates obtained using a randomly selected 10% rescreening of negative cases from the immediately preceding time period. RESULTS: The AutoPap QC System was 5.2-fold more effective for the detection of high grade squamous intraepithelial lesion + false negatives, 2.0-fold for low grade squamous intraepithelial lesions, 2.8-fold for atypical squamous cells of undetermined significance and 5.1-fold for atypical glandular cells of undetermined significance. CONCLUSION: In a large reference laboratory a QC program utilizing the AutoPap QC System was significantly more effective in the detection of false negative smears as compared to a QC program utilizing 10% random rescreening of negative smears. PMID- 9987734 TI - GnRH agonist. Increasing the pregnancy rate after combined treatment with hMG/hCG and direct intraperitoneal insemination. AB - OBJECTIVE: To evaluate the efficacy of the GnRH agonist (GnRHa) administered in conjunction with human menopausal gonadotropin/human chorionic gonadotropin hMG/hCG and direct intraperitoneal insemination (DIPI) in women with long standing unexplained infertility. STUDY DESIGN: A prospective, randomized, non blind analysis. During the period May 1995-December 1996, couples with unexplained infertility who failed to conceive following superovulation combined with IUI for at least seven cycles were prospectively enrolled and followed. Pregnancy rates per cycle and per patient of DIPI were compared between groups of hMG/hCG with (GnRHa[+] controlled ovarian hyperstimulation [COH] group) or without (GnRHa[-] COH group) GnRHa. RESULTS: Thirty-four women (59 cycles) underwent COH with hMG and GnRHa, and 31 women (49 cycles) received hyperstimulation with hMG alone. The pregnancy rates for the women administered GnRHa significantly exceeded those of the patients who did not receive GnRHa both per treatment cycle (35.6% versus 14.3%) and per couple (55.9% versus 22.5%). CONCLUSION: The use of GnRHa with hMG/hCG and DIPI treatment significantly increased the pregnancy rate in women with long-standing infertility. PMID- 9987735 TI - Polycystic ovary syndrome. Insulin resistance and ovulatory responses to clomiphene citrate. AB - OBJECTIVE: To evaluate insulin secretion detected on oral glucose tolerance testing in relation to clomiphene citrate (CC) responses in women with polycystic ovary syndrome (PCOS). STUDY DESIGN: A total of 37 PCOS women were enrolled. Plasma baseline levels of gonadotropins, sex hormone binding globulin, androstenedione, dehydroepiandrosterone sulfate and testosterone (T) were determined. Insulin and glucose serum concentrations were analyzed in all samples after a 75-g oral glucose tolerance test. A dose of 100 mg/d of CC was given for ovulation induction. Ovulation was detected by ultrasonographic observation in conjunction with a serum progesterone level. RESULTS: During three consecutive cycles of CC administration, two or more anovulatory cycles were observed in 12 of 37 PCOS women (defined as CC nonresponders). The serum T level and the area under the curve (AUC) of insulin were significantly higher in CC nonresponders. The receiver operating characteristic curve of the AUC of insulin provided the most appropriate cutoff point for the prediction of CC resistance. CONCLUSION: We found higher androgen secretion and insulin resistance in CC nonresponders. The AUC of insulin was the most reliable method for the prediction of CC resistance associated with insulin resistance. PMID- 9987736 TI - Amniotic fluid amino and nucleic acid in normal and neural tube defect pregnancies. A comparison. AB - OBJECTIVE: To explore the relationship between fetal amino acids (AAs), which are the components of structural proteins and nucleic acids, and the changes associated with neural tube defects (NTD). STUDY DESIGN: Ten weekly amniotic fluid (AF) samples from normal pregnancies (non-NTD) and 10 from NTD pregnancies between 16 and 20 weeks' gestational age were analyzed for AAs, and the weekly average for the non-NTD and NTD groups was determined. The group mean levels were compared by ANOVA. RESULTS: The weekly group mean levels of methionine, serine and aspartic acid were significantly lower than the weekly group mean levels of the other AAs. The group mean levels of methionine were significantly lower for NTD than for non-NTD pregnancies. CONCLUSION: The mean methionine level in NTD pregnancies was the only AA alteration in NTD. Although the AF levels of the non NTD pregnancies showed that the levels of serine, aspartic acid and methionine were 3- to 19-fold lower than those of the other AAs, only methionine is essential. Consequently, methionine is rate limiting with respect to the role of structural proteins and nucleic acids in the fetus. PMID- 9987737 TI - Diabetes and pregnancy. Preconception care, pregnancy outcomes, resource utilization and costs. AB - OBJECTIVE: To describe and compare pregnancy outcomes, resource utilization and costs among women with diabetes who receive and do not receive preconception care. STUDY DESIGN: A multicenter, prospective, observational study of women with type 1 diabetes who received preconception care (PC), became pregnant and delivered (PC women) and women with type 1 diabetes who received prenatal care (PC) only and delivered (PN women). RESULTS: As compared to PN women (n = 74), PC women (n = 24) were seen earlier in gestation and had significantly lower glycosylated hemoglobin levels. The combined number of outpatient visits for PC women was not greater than for PN women. PC women were hospitalized significantly less during pregnancy and tended to have shorter inpatient stays. The mean length of stay after delivery was significantly shorter for PC women. Intensity of care tended to be lower and length of stay shorter for infants of mothers who received PC care. The net cost saving associated with PC care was approximately $34,000 per patient. CONCLUSION: PC achieves its major intended health benefits and is associated with reduced resource utilization and substantially reduced costs. For both health and economic reasons, clinical practice and public policy should embrace PC. PMID- 9987738 TI - Risk factors and outcomes associated with nuchal cord. A population-based study. AB - OBJECTIVE: To assess risk factors and outcomes associated with nuchal cord at birth. STUDY DESIGN: A population-based, case-control study was conducted using linked birth and hospitalization records. Three thousand newborns were randomly selected from all singleton births with nuchal cord as noted on the birth record (n = 5,426) in King County, Washington, 1992-1993. For comparison, 3,000 controls were randomly selected from the 46,952 unaffected singleton births. RESULTS: An increased risk of nuchal cord was associated with induction of labor (odds ratio [OR] adjusted for maternal age and parity 2.0, 95% confidence interval [CI] 1.7 2.3), African American infant race (OR 1.3, 95% CI 1.0-1.6), primiparity (OR 1.2, 95% CI 1.0-1.5) and male sex (OR 1.2, 95% CI 1.0-1.3). After exclusion of selected obstetric complications, the risk of nuchal cord associated with induction of labor increased (OR 2.4, 95% CI 2.0-3.0). Nuchal cord was associated with increased risks of fetal distress (OR 2.7, 95% CI 2.1-3.4), meconium staining (OR 2.1, 95% CI 1.7-2.6), five-minute Apgar score < 7 (OR 1.6, 95% CI 1.1-2.4) and assisted ventilation < 30 minutes (OR 1.9, 95% CI 1.4-2.6). Although hospital charges for newborns with nuchal cord were slightly greater than for those without (P = .02), hospital lengths of stay did not differ significantly. CONCLUSION: Induction of labor was identified as an independent risk factor for nuchal cord. Certain adverse perinatal outcomes are increased in neonates with nuchal cord. However, neonates with nuchal cord do not have significantly longer neonatal hospital stays, and thus the adverse effects of nuchal cord may be transient. PMID- 9987739 TI - Effect of methotrexate on tubal epithelium. A report of three cases. AB - BACKGROUND: Tubal effects of methotrexate injections have been poorly reported. CASES: Three fallopian tubes were examined with light microscopy 9-13 months after tubal methotrexate injection (one case) and intramuscular methotrexate injection (two cases) given for the treatment of unruptured ectopic pregnancies. No evidence of tubal damage was found. CONCLUSION: These three cases confirm previous experimental and clinical data showing the absence of a direct adverse effect of methotrexate on the fallopian tubes in the treatment of ectopic pregnancy. PMID- 9987740 TI - Malignant hemangioendothelioma presenting as multifocal intraskeletal lesions during pregnancy. A case report. AB - BACKGROUND: Malignant hemangioendothelioma is a neoplasm of vascular origin characterized by irregular vascular channels lined with atypical endothelial cells. CASE: A gravida at 32 weeks' gestation presented with diffuse back and lower leg pain and was diagnosed with multifocal malignant hemangioendothelioma of bone. Computed tomography of the chest also demonstrated a small right atrial density. Three weeks later the patient became septic, and cesarean section was performed. After several cycles of chemotherapy, clinical improvement was noted. However, disease progression was noted thereafter, and the patient died one and a half years after the diagnosis. CONCLUSION: Our case was a primary multifocal malignant hemangioendothelioma of bone arising during pregnancy. Considering the absence of pulmonary involvement, it is unlikely that the skeletal lesions represented metastatic deposits from a cardiac primary. With such extensive skeletal disease, the right atrial density probably was a metastatic deposit. PMID- 9987741 TI - Hyperreactio luteinalis in a normal singleton pregnancy. A case report. AB - BACKGROUND: Hyperreactio luteinalis rarely occurs in normal singleton pregnancy. About 50 such cases have been published. This case is noteworthy because it resulted in extremely enlarged ovaries and was accompanied by a hyperandrogenic state and high level of human chorionic gonadotropin. CASE: A gravida was referred to our department because of large, bilateral, cystic ovaries diagnosed by ultrasonography in the 28th week of gestation. Markedly elevated levels of androgens and human chorionic gonadotropin were noted. During the following six weeks the ovarian masses enlarged, and the hyperandrogenic state worsened. Cesarean section and, because of a bleeding right adnexectomy, left ovarian resection were performed. Histology confirmed the presumed diagnosis of hyperreactio luteinalis. The placenta was unremarkable. Seventeen weeks after surgery the hormone levels were normal. CONCLUSION: Our case suggests the possibility that in certain cases of hyperreactio luteinalis, an idiopathic elevation of human chorionic gonadotropin, can occur even in normal singleton pregnancies. Furthermore, it calls attention to the necessity of ultrasonographic demonstration of ovaries even during late pregnancy. PMID- 9987742 TI - Well-differentiated endometrial adenocarcinoma in an infertility patient with later conception. A case report. AB - BACKGROUND: The incidence of well-differentiated endometrial adenocarcinoma in reproductive-age women is approximately 5%. When the women desires to retain her future fertility in light of this diagnosis, choices of surgery vs. medical therapy may present a dilemma for both the physician and patient. CASE: A young infertility patient with well-differentiated endometrial adenocarcinoma conceived by ovulation induction and intrauterine insemination after medical therapy. She subsequently delivered vaginally, and follow-up dilatation and curettage revealed no evidence of recurrent carcinoma. CONCLUSION: This case illustrates that with close observation by endometrial sampling for histologic diagnosis and follow-up, medical therapy can be an option for treating this condition to allow future fertility. The patient must be extensively counseled, however, concerning the nearly 33% chance of progression or recurrence of disease. One must also stress the importance of frequent evaluation of symptoms and endometrial pathology postpartum, with endometrial sampling as indicated and discussion of definitive surgical therapy once fertility is no longer desired. PMID- 9987743 TI - Conservative management of an 11-week cervical pregnancy. A case report. AB - BACKGROUND: Cervical pregnancy is a rare form of ectopic pregnancy. This condition is usually treated with hysterectomy. CASE: A woman with an 11.3-week cervical pregnancy was treated with methotrexate, angiographic embolization of the anterior division of the hypogastric artery, dilatation and curettage, and minimal rollerball ablation of bleeding cervical vessels only. The patient was discharged on postoperative day 1. Complications included a malodorous discharge, which was treated with oral antibiotics, and claudication of the thighs for two weeks. CONCLUSION: Advanced cervical pregnancies can be treated conservatively. PMID- 9987744 TI - Hepatocellular carcinoma in pregnancy. A case report. AB - BACKGROUND: Hepatocellular carcinoma presenting in pregnancy is very rare, and experience treating this condition is limited. Past reports have emphasized the need for pregnancy termination as part of treatment. CASE: A young, otherwise healthy woman was diagnosed with hepatocellular carcinoma in the second trimester. Her only risk factor was a six-year history of oral contraceptive use. She opted to maintain the pregnancy and was treated with surgical resection in the form of a right hepatectomy. Both she and her child were alive and well 24 months following surgery. CONCLUSION: Hepatocellular carcinoma in pregnancy can be successfully treated by surgical resection without adjuvant therapy; pregnancy termination is not mandatory. PMID- 9987745 TI - Treatment of hematotrachelos after dilatation and curettage. A case report. AB - BACKGROUND: Hematotrachelos, accumulation of menstrual blood in a dilated cervix, is a rare disorder accompanying cervical stenosis. In this report, hematotrachelos was diagnosed by vaginal sonography and treated in a novel way. CASE: A 39-year-old woman with progressive hypomenorrhea following dilation and curettage for dysfunctional uterine bleeding was diagnosed with hematotrachelos using vaginal sonography. Cervical dilatation and evacuation of the hematotrachelos were performed. A latex nasopharyngeal airway was utilized as a temporary stent and allowed drainage and maintained cervical patency. Normal menstrual flow was resumed, and the hematotrachelos did not recur. CONCLUSION: Hematotrachelos may be a rare complication of routine dilatation and curettage. The diagnosis is confirmed by transvaginal sonography. Treatment is successful with cervical dilatation and placement of a temporary latex nasopharyngeal airway. PMID- 9987746 TI - [Genetic transformation of plants, recombination processes, and gene expression regulation in transgenic plants]. AB - Recent studies in molecular biology and gene engineering were conducive to accumulation of numerous facts which help better understand the processes of plant genome functioning and follow up the effects of recombination processes in purposefully modified genome of a transformed plant on its expression. This review analyzes the major approaches to studies and results attained in plant gene engineering and plant genome imprinting. PMID- 9987747 TI - [Repression of catabolites in gram-positive and gram-negative bacteria]. AB - Analyzes the mechanism of catabolite repression of grampositive and gramnegative bacteria. The role of cyclic adenosine monophosphate and CRP protein, forming a complex, is shown. Contribution of ATP kinase to manifestation of the catabolic repression phenomenon in grampositive bacteria is discussed. PMID- 9987748 TI - [Ultrastructural and immunocytochemical study of Listeria monocytogenes with varying levels of pathogenicity factor production]. AB - Wild and mutant strains of Listeria monocytogenes are examined by electron and immunoelectron microscopy. The mutant strain was characterized as a strain with a high level of production of pathogenic factors. No essential morphological criteria permitting the differentiation between wild and mutant Listeria strains were detected. Addition of activated charcoal to nutrient medium resulted in similar morphological changes in both strains. Enlargement of cells, a thicker cell wall, and changes in the cytoplasm structure are objective morphological signs of functional activity of bacteria with a higher level of pathogenic factor production. Indirect immunocytochemical method demonstrated the localization of specific phosphatidyl inosityl phospholipase C. PMID- 9987749 TI - [Extrachromosomal genetic elements of Clostridium botulinum. II. Isolation and analysis of DNA from bacteriophages of Clostridium botulinum types C and A]. AB - The DNAs of bacteriophage c-st, known to realize the lysogenic conversion of toxinogenicity among C. botulinum types C and D strains, and the nucleic acid of a virulent mutant of bacteriophage CB propagated in type A C. botulinum cells were purified and examined. Heterogeneity of phage c-st preparations was observed during purification, manifesting by formation of several bands in isopiknic CsCl gradient during centrifuging. An extra nucleic acid fraction was detected in some DNA preparations of phage c-st; the origin of this fraction is discussed. Plasmid extrachromosomal elements were for the first time found in the cells of nontoxigenic type C C. botulinum A02 strain, known as the indicator for c-st phage. The sensitivity of phage c-st DNA to 25 restriction endonucleases was examined. Analysis of the results of restriction analysis of c-st and CB phage DNAs and plasmid nucleic acids, revealed earlier in type A C. botulinum strains, disclosed several DNA modification enzymes with different recognition sites in type C C. botulinum. At least two of these activities are not found in type A strains. According to restriction analysis, total size of phage c-st DNA is about 160 kbp and of phage CB DNA 35 kbp. Individual EcoRI and HindIII restricts of phage c-st DNA, containing the initial site of botulinum toxin CI gene, were recognized by radioisotope labeled oligonucleotide probe Enzyme immunoassay revealed slight expression of the N-terminal region of bntc I gene in E. coli recombinant variants. These data can be used in further investigation of C. botulinum genetics. PMID- 9987750 TI - [Isolation and primary characteristics of a Pseudomonas (Burkholderia) pseudomallei plasmid]. AB - Plasmid screening of reference Pseudomonas pseudomallei strains isolated from patients and animals revealed cryptic plasmids with different molecular weights in 30 strains. Plasmids were investigated by restriction analysis and DNA-DNA hybridization. Cryptic plasmids were denoted as pPM1, pCM2, pCM3, and pCM4. The presence of plasmids in melioidosis agent permits their use for intraspecies typing of strains and for genetic studies. PMID- 9987751 TI - Novel classes of Azospirillum brasilense mutants with defects in the assembly and functioning of polar and lateral flagella. AB - Azospirillum brasilense Sp245 has a mixed type of flagellation: a single polar flagellum (Fla) is synthesized constitutively, and abundant lateral flagella (Laf) are produced only in solid and semisolid media. In the present study, Omegon-Km Fla-Laf-, Fla-Laf+, Fla-/Mot-Laf-. Fla-/Mot-Laf+, Mot-Laf-, and Che- mutants of Sp245 were constructed in vivo. In some of the mutants, a number of cells possessed from 1 to 5 subpolar long flagella (Sfl). These Sfl provided the host cells with unusual motility patterns. Mutants producing shortened Fla and Laf were also detected. In the mutants still producing Laf, their expression retained the wild-type inducibility. However, all the mutants described were unable to form swarm rings in semisolid media. The results suggest the existence of common control or structural elements in assembly and rotation apparatus of both Fla and Laf systems. Single Omegon-Km insertions were localized in 85 MD (in two mutants) and in 120 MD (in one mutant) indigenous plasmids, as well as to least in two different regions of chromosomal DNA (in other mutants). PMID- 9987752 TI - [Use of a method of single-stranded DNA fragment conformation polymorphism (SSCP) for detecting resistance of Mycoplasm hominis to fluoroquinolones]. AB - Single-strand conformation polymorphism (SSCP) method was used for nucleotide sequence variation analysis of the gyrase A subunit quinolone resistance determining region (gyrA QRDR) in a laboratory and clinical strains of M. hominis. The couple of primers selected for this region amplified specific product in clinical material. M. hominis cultures growing in the presence of different concentrations of ciprofloxacin were studied by the SSCP method. Ser(83) to Leu mutation described previously was detected in the presence of quinolone in concentrations of at least 10 mcg/ml. In addition, 11 clinical samples were tested. In all cases the results of SSCP were confirmed by direct sequencing of the region. In 2 cases the sequences of gyrA QRDR in clinical strains were the same as in the laboratory strain. A Ser(83)-Leu mutation was identified in 1 clinical sample, while in others nucleotide substitutes did not lead to changes in amino acid sequences. These data demonstrate high informative value of the SSCP method for evaluating nucleotide variation in gyrA QRDR and quinolone resistance of M. hominis. PMID- 9987753 TI - Newer magnetic resonance techniques and disease activity in multiple sclerosis: new concepts and new concerns. PMID- 9987754 TI - The effect of cross-talk on MRI lesion numbers and volumes in multiple sclerosis using conventional and turbo spin-echo. AB - We measured and compared lesion numbers and volumes present on brain magnetic resonance imaging (MRI) scans of patients with multiple sclerosis (MS) acquired with contiguous (scheme A) and interleaved (scheme B) slice acquisition, to evaluate whether there was a gain in sensitivity using the second pattern of acquisition and whether this counterbalanced the doubled acquisition time. Conventional spin-echo (CSE) sequences were performed for eight patients and turbo spin-echo (TSE) sequences for ten. Acquisition scheme B detected 3.8% more lesions than acquisition scheme A (the increase was 3.1% for CSE and 4.5% for TSE). These differences were not statistically significant. No significant difference in lesion numbers was found when different lesion locations were also considered. Lesions volumes were significantly higher when scheme B was used (P = 0.024). This was due to higher lesion volumes on TSE images (P = 0.006), especially on even-numbered slices (P = 0.008). Inter-slice cross-talk has a negligible effect on lesion numbers and volume estimates in MS for CSE sequence, whilst it cannot be neglected when TSE sequences are used to measure MS lesion volume. PMID- 9987755 TI - Cerebrospinal fluid measures of disease activity in patients with multiple sclerosis. AB - The potential of magnetic resonance imaging to serve as a surrogate marker of disease activity in patients with multiple sclerosis (MS) is increasingly recognised. In contrast, the use of cerebrospinal fluid analysis has received less attention. We analysed the correlation between clinical data and cerebrospinal fluid parameters in 75 patients with acute optic neuritis (ON) as a possible first symptom of MS, as a symptom of clinically definite MS, and in patients with an attack of MS other than ON. The samples were obtained within 30 days from the onset of an exacerbation. The concentration of myelin basic protein (MBP) in cerebrospinal fluid was significantly correlated with the visual acuity in patients with ON and the Kurtzke EDSS score in patients with MS. The concentration of MBP in CSF also correlated positively with the CSF leukocyte count, intrathecal IgG synthesis, and the CSF-serum albumin concentration quotient. The concentration of MBP in CSF correlated negatively with intrathecal IgA synthesis. The results support the use of the concentration of MBP in CSF as a surrogate marker of disease activity during acute exacerbations of MS; the data also link the presence of MBP in CSF to neuroimmunological parameters. PMID- 9987756 TI - Comparing the ability of various compositive outcomes to discriminate treatment effects in MS clinical trials. The Multiple Sclerosis Collaborative Research Group (MSCRG). AB - We compared the ability of the Kurtzke Expanded Disability Status Scale (EDSS) and a composite outcome of non-physician-based measures of time to ambulate 25 feet (TA) and manual dexterity (the Box and Block Test [BBT], and 9-Hole Peg Test [9HPT]) to discriminate treatment effects in the Phase III study of interferon beta-1a. A log-rank comparison of Kaplan-Meier curves by treatment group showed the non-physician-based composite of BBT, 9HPT, and TA was of comparable sensitivity (P = 0.013) in discriminating sustained treatment failure as the EDSS alone (P = 0.029). The composite of BBT, 9HPT, TA, and EDSS was more sensitive (P = 0.009) in discriminating sustained treatment failure than the EDSS alone. Compositive outcomes of the EDSS and non-physician-based measures of manual dexterity and timed ambulation provide an appealing strategy to reduce the number of patients required to discriminate treatment effects in MS clinical trials. PMID- 9987757 TI - Side effect profile and adherence to in the treatment of multiple sclerosis with interferon beta-1a. AB - This study examines the course of patient-reported side effects during the first 4 months of treatment for multiple sclerosis (MS) with interferon beta-1a (IFN beta-1a), and the relationship of those side effects to discontinuation of medication. Flu-like symptoms, muscle aches and chills decreased over the first 2 months of treatment but did not change over the second 2 months. Loss of feeling or numbness, tingling and depression increased over 4 months, however these side effects were generally mild. Loss of feeling or numbness and tingling at 2 month follow-up were significantly related to discontinuation of IFN beta-1a by 4 month follow-up. PMID- 9987758 TI - Human Herpesvirus-6 (HHV-6) infection in multiple sclerosis: a preliminary report. AB - We examined cerebral spinal fluid (CSF) from multiple sclerosis (MS) patients and patients with other neurological diseases (OND) for antibody specific for Human Herpesvirus-6 (HHV-6) and for HHV-6 DNA detectable by PCR. CSF from MS patients had a higher frequency of IgG antibody to HHV-6 late antigens (39.4%) compared with CSF from OND (7.4%). In contrast, the frequency of detectable IgG antibody in CSF from MS patients specific for Epstein-Barr Virus (EBV) (12.1%) and Human Cytomegalovirus (HCMV) (6.1%) was much lower. Two of 12 MS CSFs (16.7%) also contained HHV-6 DNA detected by PCR. None of four OND CSF were positive for HHV-6 DNA. Plasma from 16 patients with MS, eight with OND and 72 healthy donors were tested for antibodies by ELISA to HHV-6 early (p41/38) and late (gp110) proteins. Although no differences in anti-gp110 IgG antibody were detected between MS patients, patients with other neurological diseases, and normals, IgG antibody to early protein p41/38 was detected in > 68% of the plasma from MS patients, 12.5% from OND patients and 27.8% of the controls. IgM antibody to p41/38 was present in > 56% of MS patients, 12.5% of OND patients, and 19% of controls. These data suggest that more than half of the MS patients had active, ongoing HHV-6 infections. HHV-6 was also isolated from peripheral blood mononuclear cells (PBMC) from 3/5 MS patients who were in relapse or had progressive disease and was identified as HHV-6 Variant B. These preliminary results support the hypothesis that HHV-6 may be a co-factor in the pathogenesis of some cases of MS. PMID- 9987760 TI - Olivary degeneration after intracranial haemorrhage or trauma: follow-up MRI. AB - We studied serial MRI appearances of transneuronal degeneration in the inferior olives, retrospectively analysing follow-up images of five patients, three with head injury and two with brain stem haemorrhage. We performed 13 MRI studies 4 days to 2 years 7 months after the accident. All but one of the patients exhibited bilateral olivary high signal on T2-weighted images. The interval between causal event and appearance of olivary changes was 2-4 months, images 4 days to 1.5 months after the accidents revealing no changes. Olivary enlargement was observed in four patients 2-4 months after ictus. PMID- 9987759 TI - The diagnostic value of colour duplex ultrasound for symptomatic carotid stenosis in clinical practice. AB - We assessed the accuracy of colour duplex ultrasound for the detection of severe (70-99%) symptomatic carotid stenosis in a clinical setting, in order to assess whether it could make carotid angiography unnecessary. In 152 patients with a transient ischaemic attack or nondisabling ischaemic stroke in the carotid distribution, we compared the degree of colour duplex ultrasound stenosis with angiographic stenosis by receiver-operating-characteristic analysis. The angiograms were evaluated by blinded observers, and compared with routine reports of the colour duplex examination. We computed the sensitivity and specificity of colour duplex, and the number of angiograms and sonographic studies needed to prevent one stroke within 3 years, taking into account the risks of angiography, and the risks and efficacy of endarterectomy. The estimates were adjusted for nonverification bias. We found 34 patients (22%) with a severe (70-99%) symptomatic carotid stenosis. In 16 patients (11%) the symptomatic artery was occluded. The sensitivity and specificity of duplex ultrasound were 76% and 85%, respectively. The number of patients needed to undergo angiography to prevent one stroke was reduced from almost 200 to 33, when colour duplex was used as a preoperative examination. After adjustment for the effects of nonverification, the sensitivity dropped to 58% and the number of duplex studies needed to prevent one stroke would double. The number of angiograms needed after positive duplex sonography would be virtually unaffected. Were colour duplex sonography to have been the sole preoperative investigation, the number needed to diagnose to prevent one stroke within 3 years would be approximately 350, more than twice as many as with the combined diagnostic strategy. The diagnostic accuracy of colour duplex sonography in clinical practice seems less impressive than previous studies have suggested, but it remains an effective way to select patients for angiography. Its use as a single preoperative assessment cannot be recommended. PMID- 9987761 TI - Cystic lesions accompanying extra-axial tumours. AB - We examined the mechanism of cyst formation in extra-axial tumours in the central nervous system (CNS). Cyst fluid, cerebrospinal fluid (CSF) and blood plasma were analysed in eight patients with nine peritumoral cysts: four with meningiomas, two with intracranial and two spinal intradural schwannomas. Measuring concentrations of various proteins [albumin, immunoglobulin G (IgG), IgA, alpha 2 macroglobulin and IgM] in cyst fluid, CSF and blood plasma provides insight into the state of the semipermeability of the blood-brain barrier (BBB) and blood cerebrospinal fluid barrier. Peritumoral cysts accompanying intra-axial brain tumours are the end result of disruption of the BBB and oedema formation. Unlike intra-axial tumours which lie embedded within nervous tissue, extra-axial tumours tend to be separated from nervous tissue by arachnoid and pia mater. High concentrations of proteins were measured in the cyst fluid, approaching blood plasma levels, suggesting a local barrier disruption, and passage across the arachnoid, pia mater and cortical/medullary layer into the CNS parenchyma, leaving the protein concentrations of CSF practically unchanged. We confirmed that very high concentrations of protein are to be found in tumour cysts, plasma proteins forming almost 90% of the total protein in the cyst. We review current hypotheses on the pathogenesis of cysts accompanying neoplasms, particularly meningiomas and schwannomas, and conclude that the majority of proteins in cyst fluid in extra-axial, intradural meningiomas and schwannomas are plasma proteins. This provides a strong argument for pathogenesis of extra-axial intradural tumour cysts in favour of leakage of plasma proteins out of the tumour vessels into the nervous tissue. PMID- 9987762 TI - Fibro-osseous lesions involving the brain: MRI. AB - We present the MRI findings in two patients with "fibro-osseous lesions" involving the central nervous system. A left temporal lobe mass was present in one patient and an extra-axial mass at the skull base in the other. In both cases, calcification was present, with low signal intensity on T1- and T2 weighted images. PMID- 9987763 TI - Pituitary macroadenoma and diaphragma sellae meningioma: differential diagnosis on MRI. AB - Diaphragma sellae meningiomas are unusual tumours often not distinguished from pituitary macroadenomas. Preoperative differentiation is essential, because the trans-sphenoidal approach is used for surgical removal of adenomas, while meningiomas are approached via a craniotomy. We reviewed five patients in whom a diaphragma sellae meningioma was initially diagnosed as a nonsecreting pituitary macroadenoma. MRI criteria for differential diagnosis are discussed. The main findings considered are visibility of the pituitary gland, contrast enhancement, the centre of the lesion and sellar enlargement. These criteria, applied to a blind review, allow correct identification of the tumours. PMID- 9987764 TI - Spontaneous regression of a pituitary cyst. AB - We present a pituitary cyst discovered on MRI in an amenorrheic patient that regressed over months. Although the precise etiology of the cyst is unproven, documentation of pituitary cyst regression has not to our knowledge been described previously. PMID- 9987765 TI - Pleomorphic xanthoastrocytoma with CT and MRI appearance of meningioma. AB - We describe a pleomorphic xanthoastrocytoma (PXA) in a young girls whose frontal lobe location, solid structure, dural tail and MRI signal characteristics led to a preoperative diagnosis of meningioma. PXA should be considered in differential diagnosis of tumours affecting young patients with neuroradiological characteristics suggestive of meningioma. PMID- 9987766 TI - Intracranial leiomyosarcoma in a patient with AIDS. AB - We report an intracranial leiomyosarcoma in the pontine cistern of a 34-year-old woman infected with the human immunodeficiency virus (HIV). The clinical, radiological and pathological data are reviewed. The tumor was Epstein-Barr virus (EBV) positive by in situ hybridization. This case emphasizes that smooth muscle neoplasms arising in the setting of immunocompromise can occur intracranially, and corroborates a hypothesis that EBV coinfection may have a role in development of these tumors. PMID- 9987767 TI - Marchiafava-Bignami disease with widespread extracallosal lesions and favourable course. AB - We report a 61-year-old alcoholic man who presented with subacute physical deterioration and severe dysarthria. MRI, suggestive of corpus callosum demyelination with associated white matter involvement in both cerebral hemispheres, indicated the diagnosis of Marchiafava-Bignami disease. During his stay in hospital the patient showed remarkable improvement, and was discharged 22 days after admission. On MRI 2 months later, the extracallosal lesions had disappeared. This case raises questions about some previous ideas on this disease, such as the prognosis of its acute forms and the significance of the extracallosal lesions seen on neuroimaging. PMID- 9987768 TI - Unusually exuberant hyperostosis frontalis interna: MRI. PMID- 9987769 TI - 3D T2-weighted fast spin-echo MRI sialography of the parotid gland. AB - The diagnostic value of 3D T2-weighted MRI sialography and 2D T2-weighted fast spin-echo (FSE) images for delineation of the normal duct system and characterisation of parotid gland duct pathology was compared in a prospective study. We studied eight healthy volunteers and 18 patients with pathology of the parotid gland (tumours in 3, sialolithiasis in 6, Sjogren's disease in 4, recurrent or chronic parotitis in 4, post-traumatic stricture of the main parotid duct in 1). A heavily T2-weighted 3D FSE sequence was compared with a conventional 2D T2-weighted FSE sequence. The normal main parotid duct was always visible on 3D sialography and seen in 68% of the 2D T2-weighted FSE studies. The diagnostic reliability of both sequences for diagnosis of luminal concretions in sialolithiasis and dilatation of the duct in duct stricture or chronic parotitis was equal, although slight intraglandular dilatation was appreciated only on 3D sialography. Extraductal pathology resulting in obstruction or displacement of ducts was better characterised on 2D T2-weighted images. However, 3D MRI sialography offered the advantage of postprocessing with overview images and multiple maximum-intensity projection images in any plane. PMID- 9987770 TI - Solitary fibrous tumor of the orbit: CT and pathologic correlation. AB - We report the CT findings of a solitary fibrous tumor of the orbit. The radiologic features included relatively homogeneous contrast enhancement and smooth remodelling of the bones of the orbit, findings consistent with the benign nature of this relatively rare tumor. PMID- 9987771 TI - The oculocerebrocutaneous (Delleman-Oorthuys) syndrome. AB - We describe two cases of the so-called oculocerebrocutaneous syndrome, also known as the Delleman-Oorthuys syndrome. Both patients had characteristic congenital anomalies of the orbit, central nervous system and skin. The ocular and cerebral lesions were studied with CT and MRI. PMID- 9987772 TI - Endovascular treatment of aneurysms on the feeding arteries of intracranial arteriovenous malformations. AB - The association between intracranial aneurysms and arteriovenous malformations (AVMs) is well documented. Recent advances in the understanding of the haemodynamics of this association encourage an aggressive approach to these aneurysms. However, the pathophysiology of these aneurysms is not fully understood and a strategy for their management has not been established. We describe seven patients, with eight aneurysms, on the feeding arteries of AVMs. The aneurysms could be divided into those located 1. proximally on the superficial feeding artery (type I; 4 aneurysms); 2. distally on the superficial feeding artery (type II; 3 aneurysms); and 3. on the deep feeding artery (type III; 1 aneurysm). All aneurysms were treated by the endovascular procedure prior to, or simultaneously with, treatment of the AVM, using detachable coils or liquid embolic material. All aneurysms were obliterated successfully, with no adverse events. Each patient further received treatment of the AVM. None of the patients suffered intracranial haemorrhage after treatment for the aneurysms. Based on our experiences, we discuss the indications for this approach for each type of aneurysm. We believe endovascular treatment could be an important alternative for treatment of aneurysms associated with AVMs, thus reducing the risk of haemorrhage. PMID- 9987773 TI - Failure to demonstrate a direct caroticocavernous fistula due to arterialisation of the ipsilateral cavernous sinus. AB - We report a woman in whom a small direct caroticocavernous fistula (DCCF) was revealed after successful transarterial occlusion of a contralateral fistula which drained into both cavernous sinuses. We underline that a second smaller fistula can be masked by a contralateral larger one due to the lack of pressure gradient between the internal carotid artery (ICA) and arterialised blood in the ipsilateral cavernous sinus. We suggest that bilateral ICA angiograms should be performed before and after occlusion of all DCCF. PMID- 9987774 TI - [Iodine deficiency disorders with functional autonomy. Diagnostic and therapeutic indications]. PMID- 9987775 TI - [F-18-FDG PET in autonomous goiter]. AB - AIM: Gain-of-function mutations of the thyrotropin receptor (TSHR) gene have been invoked as one of the major causes of toxic thyroid adenomas. This study evaluates F-18-FDG-PET in these patients. METHODS: Twenty patients with focal autonomous nodules and ten with disseminated autonomy were investigated the day before radioiodine therapy. Twenty patients with cancer of the head or neck and normal thyroid function served as controls. RESULTS: F-18-FDG-Uptake was higher in patients than in controls. Focal autonomous nodules were associated with focally enhanced glucose metabolism. Disseminated autonomous goiters showed various patterns of focal or global hypermetabolism. CONCLUSION: Autonomous thyroid tissue caused by constitutive mutations of the TSH receptor is characterised by simultaneous increases in glucose and iodine metabolism which are correlated. PMID- 9987776 TI - [Cost-effectiveness analysis: radioiodine or antithyroid medication in primary treatment of immune hyperthyroidism]. AB - AIM: As first-line therapy of hyperthyroidism caused by Graves' disease antithyroid drugs are favoured in Europe, while radioiodine therapy is favoured in the USA. Radioiodine therapy has become more economic in Germany since the new recommendations by the Federal German Radiation Protection Committee (SSK) for patient discharge guidelines. METHOD: Sensitivity analyses took into account the long-term relapse rate of conservative or radioiodine therapy, use of diagnostic tests, level of health insurance, drops in productivity and a discount factor. Costing models included the costs of follow-up care over 30 years. The costs of the hospitalisation for radioiodine therapy were calculated for 300 patients, discharged with 250 MBq 1-131 residual activity. RESULT: Antithyroid drugs were considered cost-effective when they achieved relapse rate of 50% or less, a cut in the number of tests needed and reduced working hours. Failure to meet any one of these conditions makes primary radioiodine therapy more cost-effective in 1593 of 1944 calculated costing models. Repeated conservative therapies will increase clearly the overall costs. CONCLUSION: Radioiodine is a cost-effective, first line therapy in patients with a special risk of relapse after primary conservative therapy (goitre, younger patient, persistent elevated TSH-receptor antibodies or Tc-uptake). PMID- 9987777 TI - [Somatostatin receptor status in non-medullary thyroid carcinoma]. AB - AIM: Recent in-vitro and in-vivo studies demonstrated a somatostatin receptor expression in some non-medullary thyroid carcinomas. In this study we investigated the somatostatin receptor status for this particular tumor entity in a larger patient group. SUBJECT AND METHODS: We compared 131-iodine with 111-In pentetreotide scans in 24 patients with metastasizing, non-medullary thyroid cancer. The findings were correlated with other imaging modalities. Additionally, we performed receptor autoradiography in one patient, octreotide therapy in another patient and administration of 90-Y- and 111-In-DOTATOC in 2 consecutive patients. RESULTS: In the 15 patients with papillary or follicular carcinoma, 111 In-pentetreotide was inferior to 131-I in 8/15, equal in 1/15, and superior in 6/15 patients. In 8/9 of the patients with Hurthle cell carcinoma, metastases showed a 111-In-pentetreotide accumulation of various intensity, while 131-iodine scans were negative except for one patient. 111-In-pentetreotide was equal or superior compared to 201-Tl or 99m-Tc-sestamibi, but for the most part inferior in comparison with 18-F-FDG-PET. The findings of 111-In-pentetreotide scintigraphy correlated well with the receptor autoradiography and the accumulation of DOTATOC, but not with the therapeutic effect of "cold" octreotide on the thyroid cancer metastases. CONCLUSIONS: Several metastases of papillary and follicular carcinoma, and the majority of Hurthle cell cancer metastases can express somatostatin receptors. 111-In-pentetreotide scintigraphy is a promising tool for localization of metastases especially in Hurthle cell cancer or if PET is not available, and may be useful for selection of possible candidates, if therapeutic effective beta-emitting somatostatin analogues will be available for routine application. PMID- 9987778 TI - [Clinical value of FDG PET for therapy monitoring of malignant lymphoma--results of a retrospective study in 72 patients]. AB - AIM: Of the present retrospective study was to validate the clinical value of FDG PET for therapy control of malignant lymphoma. METHOD: 72 patients (41 non Hodgkin lymphomas, 29 Hodgkin's disease, 2 unclassified) received static FDG-PET scans of initially involved regions (n = 53) or of the entire neck and trunk (n = 19) after therapy. CT imaging (n = 70) and serum LDH measurement (n = 64) were also performed. Results were validated either by biopsy (n = 7) or by clinical follow-up (n = 65). The predictive value of PET was analysed in relation to different prognostic factors (stage, recurrence status, number of prior therapy regimen). RESULTS: PET obtained a sensitivity of 88%, a specificity of 83% and an overall accuracy of 85% for detection of residual disease. The values for CT were 84%, 31% resp. 54%, and for serum LDH 50%, 92% and 73%. The predictive value of PET was related to the prevalence of residual disease. PET predicted complete remission in more than 90% of patients with moderate risk (stage I-III, no relapse, no more than two different therapy regimens). In high risk patients, however, the negative predictive value of PET was 50-67%. CONCLUSION: FDG-PET is more accurate than CT imaging and LDH measurement for therapy monitoring of malignant lymphoma. Therapy success can be reliably predicted in patients with moderate risk. PMID- 9987779 TI - [Radioiodine therapy in veterinary medicine: treatment of hyperthyroidism in a cat]. AB - A nine-year-old cat with symptoms of a distinct hyperthyroidism was presented at the University Hospital of the RWTH Aachen. The clinical symptoms as well as the diagnostic procedures performed at the hospital confirmed the diagnosis. After five weeks of thyreostatic medication a regular metabolism of the thyroid gland was established, followed by a radioiodine therapy with 70.3 MBq 131-iodine. Subsequently, the cat was hospitalized for two days before it could be released in good condition. Six weeks after treatment the former drastically reduced weight of the cat recovered to near normal. Even though the chemical analysis detected a discrete hyperthyroidism, clinical symptoms were no longer prominent. Three months after treatment, the final examination showed a regular metabolism of the thyroid gland without a specific thyroidal medication. The presented case illustrates that radioiodine therapy is a safe and efficient treatment of thyroidal dysfunctions in veterinary medicine. PMID- 9987780 TI - [Thyroid gland hemiagenesis with Graves' disease]. AB - A case of Graves' disease occurring in a patient with hemiagenesis is presented. The detection of the rare occurrence of a congenital hemiagenesis is often made by either clinical symptoms of thyroid dysfunction or anatomical abnormalities such as nodular goiter. The symptoms of hyperthyroidism in the current case led to the diagnostic confirmation by scintiscanning and ultrasonography of an absent lobe. Anti-thyroid antibody studies documented the presence of Graves' disease within the remaining lobe. PMID- 9987781 TI - Kill the messenger! PMID- 9987782 TI - A history of placental dysfunction and risk of placental abruption. AB - In a population-based historic cohort study, we assessed the possible association of fetal growth retardation, preterm birth and pregnancy-induced hypertension in the immediately preceding pregnancy with placental abruption in the current pregnancy, which would suggest a shared aetiological factor. We also assessed whether chronic hypertension, diabetes mellitus and a history of Caesarean section are associated with placental abruption. Preterm birth and small-for gestational-age (SGA) in the immediately preceding delivery were associated with an increased risk of placental abruption with unadjusted odds ratios (ORs) of 2.1 [95% CI = 1.9, 2.4] and 1.6 [95% CI = 1.5, 1.8] respectively. Women with a history of an SGA preterm birth in the immediately preceding delivery and an appropriate-for-gestational-age infant in the current had an adjusted OR of 3.2 [95% CI = 2.3, 4.5]. The adjusted odds ratio of placental abruption in women who had pregnancy-induced hypertension in the previous pregnancy, but not in the current, was 1.4 [95% CI = 1.2, 1.7]. Women who delivered a preterm or SGA infant in the previous delivery and had chronic hypertension or diabetes mellitus in the current had adjusted ORs of 2.3-5.7 and 2.5-6.0 respectively. Caesarean section in the previous delivery increased the risk of placental abruption by 40%. These results suggest that pregnancy-induced hypertension, intrauterine growth retardation, preterm delivery and placental abruption share an aetiological factor or represent different clinical expressions of recurring placental dysfunction. Chronic hypertension and diabetes mellitus may cause or aggravate such dysfunction thus causing placental abruption. A history of Caesarean section is associated with an increased risk of placental abruption. PMID- 9987783 TI - Smoking and blood pressure patterns in normotensive pregnant women. AB - This paper examines the relationship between smoking levels and blood pressure patterns of normotensive pregnant women in a prospective cohort of 2193 primiparous and 3176 multiparous, normotensive, Caucasian women selected from the Child Health and Development Studies in Oakland, California, 1959-67. Regression lines were fitted to each woman's blood pressure; mean intercept and slope estimates of the individual regressions were used to create summary profile lines for each smoking dose. Multivariable regression analysis controlled for maternal age, number of visits to the doctor after 20 weeks' gestation, body mass index and maternal education level. Overall, smokers had lower average diastolic blood pressure (smokers vs. nonsmokers adjusted mean: primiparas, 66.1 vs. 67.2 mmHg; and multiparas, 64.0 vs. 64.7 mmHg) but higher systolic blood pressure (smokers vs. nonsmokers adjusted mean: primiparas, 117.0 vs. 116.0; and multiparas, 112.5 vs. 110.0) than nonsmokers among primiparous and multiparous pregnant women after adjusting for potential confounders. However, these differences are small and there was no clear dose-response relationship between smoking level and blood pressure. PMID- 9987784 TI - Evidence for an association between environmental tobacco smoke exposure and birthweight: a meta-analysis and new data. AB - Because of the strong association of active smoking with fetal growth retardation, increasing interest has focused on whether there is also an association with exposure to environmental tobacco smoke (ETS). We examined this issue in a retrospective study and by conducting a review of the literature and data pooling. In our study, nonsmoking women with singleton livebirths born in 1986-87 (n = 992) provided information on exposure to ETS for 1 h or more per day and paternal smoking. The risk of low birthweight (LBW, < 2500 g) was not increased in infants of ETS-exposed women, but there was a somewhat increased risk for LBW at term (adjusted odds ratio [OR] 1.8, 95% confidence interval [CI] 0.6, 4.8) and small-for-gestational-age (< 10th percentile of weight; OR = 1.4, 95% CI = 0.8, 2.5). These results were in the range of 16 other studies in the literature that had odds ratios from 1.0 to 2.2. A weighted average of the results of all studies on LBW at term or small-for-gestational-age yielded a pooled estimate of 1.2 [95% CI = 1.1, 1.3] in nonsmoking women. The pooled estimate of mean birthweight indicated a decrement of 28 g with ETS exposure of nonsmoking women [95% CI = -41, -16], with a greater decrement (about 40 g) seen among more homogeneous studies. PMID- 9987785 TI - A lower rate of preterm birth after clotrimazole therapy during pregnancy. AB - Topical or vaginal clotrimazole treatment during pregnancy was evaluated in the large population-based control data set of the Hungarian Case-Control Surveillance of Congenital Abnormalities, 1980-92. The database comprised 32,804 control non-malformed newborn infants, 7.7% of whom were born to mothers who had received clotrimazole treatment during pregnancy. An increase in mean gestational age among exposed vs. unexposed was found. It is postulated that the use of clotrimazole during pregnancy reduced significantly the proportion of preterm births because of the effective treatment of genital infections caused by candidiasis in pregnant women. PMID- 9987786 TI - Sociodemographic determinants of low birthweight in Greece: a population study. AB - A total population sample of 10,654 singleton births from the Greek National Perinatal Survey of April 1983 was analysed to identify factors independently associated with low birthweight (LBW). The sample was divided into two groups according to the gravidity of the mothers (3368 primigravidae and 7286 multigravidae). Data examined included regional characteristics, marital status, age at and duration of marriage, parental ages at delivery, crowding in the home, insurance status, parental occupational classification and parental education levels. Logistic regression was used to define the socio-economic and demographic characteristics independently associated with the delivery of an LBW singleton baby. Significantly different LBW rates were found among the two groups: 4.3% in the primigravidae and 5.2% for multigravidae. For primigravidae significant associations were found with marital status, maternal occupation and father's education, while for multigravidae significant features were mother's education and place (region) of residence. The study showed little to assist in devising strategies of primary prevention of LBW in Greece. PMID- 9987787 TI - Repeated neonatal deaths in families with special reference to causes of death. AB - It is recognized that one infant death in a family indicates an increased risk of death of a subsequent sibling. This study examines which cause of death of a sibling is related to the mortality of the younger sibling and when. Longitudinal vital events data from the maternal and child health and family planning (MCH-FP) project and the comparison areas in Matlab, Bangladesh, were used. Primary causes of 868 neonatal deaths and 624 post-neonatal deaths resulting from 18,865 singleton live births in 1989-92 and those (967 as neonates and 708 as post neonates) of their immediate elder siblings were categorised into infectious and non-infectious diseases. Multinomial logistic regression was used to estimate the risk of younger siblings dying in each age period from infectious and non infectious diseases given the age and cause of deaths of older siblings and controlling for other biosocial correlates of infant mortality. A neonatal death of non-infectious causes in a family was twice as likely to be followed by another one occurring at the same age from similar causes compared with a surviving infant followed by a neonatal death from non-infectious causes. The MCH FP project, though successful in reducing the risk of neonatal and post-neonatal mortality from infectious diseases, did not reduce the risk of dying from non infectious diseases. PMID- 9987788 TI - Ascaris-Trichuris association and malnutrition in Brazilian children. AB - This work was designed to evaluate the role of intestinal parasites on nutritional status in three rural areas of Brazil. A total of 520 children aged 1 12 years were studied through a questionnaire concerning housing, socio-economic conditions and a 24-h food intake recall. Measurements of weight and height were also performed, and three stool samples were collected on consecutive days for parasitological analysis. Scores of the standard deviation (z-scores) for the weight-for-height and height-for-age were used to characterise the growth profile. A high prevalence of intestinal parasites was detected, with Giardia lamblia (44%), Endolimax nana (43%), Ascaris lumbricoides (41%) and Trichuris trichiura (40%) being the most prevalent. Eleven per cent of the children were classified as showing stunting. Inadequate daily caloric intake was observed in 78% of the population and the proportion of those with inadequate protein intake was 34%. Logistic regression analysis was employed for the multivariate study. Stunting was significantly associated with estimators of low economic income, inadequate protein intake and polyparasitism, especially the association between Ascaris lumbricoides and Trichuris trichiura. PMID- 9987789 TI - Validation of caregiver interviews to diagnose common causes of severe neonatal illness. AB - The objective of this study was to validate retrospective caregiver interviews for diagnosing major causes of severe neonatal illness and death. A convenience sample of 149 infants aged < 28 days with one or more suspected diagnoses of interest (low birthweight/severe malnutrition, preterm birth, birth asphyxia, birth trauma, neonatal tetanus, pneumonia, meningitis, septicaemia, diarrhoea, congenital malformation or injury) was taken from patients admitted to two hospitals in Dhaka, Bangladesh. Study paediatricians performed a standardised history and physical examination and ordered laboratory and radiographic tests according to study criteria. With a median interval of 64.5 days after death or hospital discharge, caregivers of 118 (79%) infants were interviewed about their child's illness. Using reference diagnoses based on predefined clinical and laboratory criteria, the sensitivity and specificity of particular combinations of signs (algorithms) reported by the caregivers were ascertained. Sufficient numbers of children with five reference standard diagnoses were studied to validate caregiver reports. Algorithms with sensitivity and specificity > 80% were identified for neonatal tetanus, low birthweight/severe malnutrition and preterm delivery. Algorithms with specificities > 80% for birth asphyxia and pneumonia had sensitivities < 70%, or alternatively had high sensitivity with lower specificity. In settings with limited access to medical care, retrospective caregiver interviews provide a valid means of diagnosing several of the most common causes of severe neonatal illness and death. PMID- 9987790 TI - Determinants of participation in an epidemiological study of preterm delivery. AB - We describe the study design and patterns of participation for a cohort study of preterm delivery, focused on genital tract infections, nutrition, tobacco use, illicit drugs and psychosocial stress. Women are recruited at 24-29 weeks' gestation from prenatal clinics at a teaching hospital and a county health department. We recruited 57% of the first 1843 eligible women; 29% refused and 8% could not be contacted. White women were somewhat more likely to participate than African-American women (61% vs. 54% respectively). More notable differences were found comparing teaching hospital and health department clinics (71% vs. 47% participation respectively), with the health department clinic having a greater proportion refuse (24% vs. 33%) and more women who could not be contacted (4% vs. 11%). Participation was affected only minimally by day or timing of recruitment, but inability to contact diminished substantially as the study continued (13-0%). Refusals were largely unrelated to patient attributes. Lower education predicted inability to contact. Risk of preterm delivery was 14% among recruited women, 10% among women who refused, and 15% among women whom we were not able to contact, demonstrating that, overall, risk status was not lower among recruited women. PMID- 9987791 TI - The five syndromes and more. PMID- 9987792 TI - Norbornane compounds in pharmaceutical research. PMID- 9987793 TI - Synthesis of novel 4,5-diphenylthiazole derivatives as potential acyl CoA:cholesterol O-acyltransferase inhibitors. AB - Several novel N-(4,5-diphenylthiazol-2-yl)-N'-aryl or alkyl (thio)ureas and N (4,5-diphenylthiazol-2-yl)alkanamides were prepared as potential acyl-CoA: cholesterol O-acyltransferase (ACAT) inhibitors. Synthesis was accomplished by reaction of 2-amino-4,5-diphenylthiazole with the suitable isocyanate, isothiocyanate or acyl chloride. Some analogues without the 5-phenyl substituent or both the phenyl groups in 4 and 5 position of the thiazole ring were also prepared. Moreover, some bioisosters of the title compounds in which the thiazole ring was replaced by an imidazole were synthesized starting from the 2-amino-4,5 diphenyl-1H-imidazole. The ability of synthesized compounds to inhibit ACAT was evaluated in vitro by measuring the formation of cholesteryl[14C]oleate from cholesterol and [1-14C]oleoyl-CoA in rat liver microsomes. Among the tested compounds, only some thiazole ureas were able to inhibit ACAT in a reasonable degree. N-(4,5-diphenylthiazol-2-yl)- N'-[2,6-bis(2-methylethyl)phenyl] urea (11) and N-(4,5-diphenylthiazol-2-yl)-N'-n-butyl urea (16) were the most active compounds in the series showing IC50 values in the low micromolar range. PMID- 9987795 TI - Synthesis and biological activity of new diarylalkenes. AB - Condensation of 5-nitro, 3-chloro-, and 5-chlorosalicylic acid with formaldehyde afforded dimeric disalicylmethanes which were O-methylated with dimethyl sulfate and oxidized with chromium(VI) oxide to give the diarylketones 10, 11, 12. Wittig reaction with ylides obtained by deprotonation of alkyltriphenylphosphonium salts with sodium bis (trimethylsilyl)amide yielded a series of diarylalkenes. Some of the obtained compounds showed high antimicrobial activity in vitro against Bacillus subtilis and Mycobacterium smegmatis. PMID- 9987794 TI - Synthesis and antituberculosis activity of new 2-quinoxalinecarbonitrile 1,4-di-N oxides. AB - With the advent of multidrug-resistant Mycobacterium tuberculosis strains, new and effective therapies are rapidly needed to combat infections caused by these strains. Some new 2-quinoxalinecarbonitrile 1,4-di-N-oxides have been synthesized and tested as antituberculosis agents and interesting results have been obtained from the first screening. PMID- 9987796 TI - Study of local anaesthetics, Part 146: Correlation between local anaesthesia, coded structural information, and chromatographic properties for homologous series of alkoxysubstituted esters of phenylcarbamic acid using a neural network. AB - RP HPLC capacity factors were used for the characterisation of the lipophilicity of homologous series of o- and m- alkoxy-substituted pyrolidino-, piperidino-, and N-methylpiperazino esters of phenylcarbamic acid. The mathematical method of a neural network was employed for supplementing of the incomplete original data matrix and for smoothing the biological data. The dependencies of the number of carbon atoms in the alkoxy side chain (resp. LC capacity factors) on the surface anaesthesia for the homologous series have parabolic character. The surface anaesthetic activity of the o-alkoxy-substituted derivatives was higher than that of m-alkoxy-substituted derivatives. m-Alkoxy-substituted esters presented maxima of activity at 6 and o-derivatives at 7 carbon atoms in the alkoxy side chain. PMID- 9987797 TI - Ocular delivery systems of pefloxacin mesylate. AB - Ocular films of pefloxacin mesylate were prepared with the objectives of reducing the frequency of administration, to improve patient compliance, obtaining controlled release and greater therapeutic efficacy in the treatment of eye infections such as conjunctivitis, keratitis, kerato conjunctivitis, corneal ulcers etc. Polymers such as HPC, HPMC, PVP and PVA were used in different ratios to prepare the ocular films. They were evaluated for drug content which varied from 96-104%. Those which consisted of flexible and transparent films were subjected to in vitro release studies. The formulations which prolonged the release for eight hours were selected. The average weight and thickness of these were found to be 38.92-49.71 mg and 31.68-46.08 microns, respectively. The intactness of the formulations was confirmed by IR and TLC studies. In vivo studies carried out in the eyes of rabbits showed controlled release upto 8-9 h. There was a good correlation between the in vitro and in vivo data (r = 0.97 0.995). A minimum of 1 Mrad was found to be necessary for the sterilization of ocular films by gamma radiation. They were found to be stable at temperatures below 45 degrees C. PMID- 9987798 TI - Loteprednol etabonate, a new soft steroid is effective in a rabbit acute experimental model for arthritis. AB - Loteprednol etabonate, a new soft steroid designed for use as a local therapeutic, was compared to dexamethasone in rabbit experimental model for arthritis. METHODS: Joint inflammation was induced by local injection of antigen into the patellofemoral articulation in sensitized rabbits. Co-administration of either dexamethasone or loteprednol etabonate directly into the joint effectively blocked the inflammatory response. Both the synovial fluid cellular content and synovium histology were examined. The steroid treatments prevented the adverse inflammatory effects of antigen action. These results, together with previous studies showing decreased systemic activity of the soft steroid, indicate that the loteprednol etabonate could provide a therapeutic advantage over currently used intra-articular steroids for alleviating rheumatoid arthritis. PMID- 9987799 TI - The new antiarrhythmic substance AWD 23-111 inhibits the delayed rectifier potassium current (IK) in guinea pig ventricular myocytes. AB - The effects of N-(dicyclohexyl-carbamoylmethyl)-N-(3-diethylamino-propyl)-4-nitro -benzamide hydrochloride (AWD 23-111), a novel antiarrhythmic compound, were studied in isolated cardiomyocytes of guinea pigs. Using whole-cell configuration of the patch-clamp technique AWD 23-111 was tested for its ability to block the delayed rectifier potassium channel (IK). In guinea pig ventricular myocytes the current is composed of two components: IKr, a rapidly activating current and IKs, a slowly activating component which were discriminated by their different activation and deactivation behaviour. In this preparation AWD 23-111 displayed concentration dependent inhibitory effects on IKr as well as on IKs in the tested concentration range between 1 and 100 mumol/l. This blocking effect was independent of the stimulation frequency (0.2, 1 and 2 Hz). There was no influence of AWD 23-111 on the amplitude of L-type calcium whole-cell currents. The compound significantly prolonged action potential duration (APD) at a stimulation frequency of 2 Hz (1 and 10 mumol/l). At 0.2 Hz there was no effect on APD. Our results suggest that AWD 23-111 blocks both components of IK without a reverse use-dependent effect on APD which limits the therapeutic potential of most other class III agents. PMID- 9987800 TI - Can diastereoisomerism of alkoxyphenylcarbamates influence their local anesthetic activity? AB - The surface local anesthetic activity (LAA) in the homologous series of racemic (+/-)-cis- and (+/-)-trans-N,N-dimethyl-2- (2 alkoxyphenylcarbamoyloxy)cyclopentylmethylamonium chlorides was evaluated. The potency was expressed in rabbits as efficiency indices (EI) in comparison to the standard drug cocaine. All tested racemic mixtures of the phenylcarbamates were local anesthetically active and their potency increased with the size of alkoxysubstitution from the propyloxy- to the hexyloxyderivative and then decreased abruptly (cut-off effect). When different mixtures of both diastereoisomers were applied the synergistic effect--i.e. increase of the LAA of one diastereomer when adding the other--was observed. It seems that an optimal racemic ratio of the compounds could increase their local anesthetic efficiency. PMID- 9987801 TI - In vitro effect of imipenem on Acinetobacter baumannii. AB - Imipenem at suprainhibitory concentrations (2x, 4x or 8x MIC) induced postantibiotic effects (PAEs) (suppression of bacterial growth after a short time exposure of bacteria to antimicrobials) against two of three Acinetobacter baumannii strains. The highest concentration tested demonstrated the longest delay of bacterial regrowth (1.7 h (strain 5570) or 3.9 h (strain 6070)). All. A. baumannii strains showed changes in surface hydrophobicity and serum sensitivity after treatment with imipenem. The antibiotic at 8x MIC reduced hydrophobicity of the strains most significantly (from 42.3%-72.0%) as compared to controls (without antibiotic). Susceptibility of the treated bacteria to serum bactericidal activity has also been lowered. Though imipenem suppressed bacterial growth and decreased surface hydrophobicity of the bacteria, it increased survival of bacteria after incubation with serum. These different alterations observed in the studied strains should be taken into account when evaluating the effects of imipenem. PMID- 9987802 TI - Determination of pefloxacin in serum by time-resolved fluorimetry. PMID- 9987803 TI - Effects of Quercus ilex L. and Punica granatum L. polyphenols against ethanol induced gastric damage in rats. PMID- 9987804 TI - The induction of pain: an integrative review. AB - The highly disagreeable sensation of pain results from an extraordinarily complex and interactive series of mechanisms integrated at all levels of the neuroaxis, from the periphery, via the dorsal horn to higher cerebral structures. Pain is usually elicited by the activation of specific nociceptors ('nociceptive pain'). However, it may also result from injury to sensory fibres, or from damage to the CNS itself ('neuropathic pain'). Although acute and subchronic, nociceptive pain fulfils a warning role, chronic and/or severe nociceptive and neuropathic pain is maladaptive. Recent years have seen a progressive unravelling of the neuroanatomical circuits and cellular mechanisms underlying the induction of pain. In addition to familiar inflammatory mediators, such as prostaglandins and bradykinin, potentially-important, pronociceptive roles have been proposed for a variety of 'exotic' species, including protons, ATP, cytokines, neurotrophins (growth factors) and nitric oxide. Further, both in the periphery and in the CNS, non-neuronal glial and immunecompetent cells have been shown to play a modulatory role in the response to inflammation and injury, and in processes modifying nociception. In the dorsal horn of the spinal cord, wherein the primary processing of nociceptive information occurs, N-methyl-D-aspartate receptors are activated by glutamate released from nocisponsive afferent fibres. Their activation plays a key role in the induction of neuronal sensitization, a process underlying prolonged painful states. In addition, upon peripheral nerve injury, a reduction of inhibitory interneurone tone in the dorsal horn exacerbates sensitized states and further enhance nociception. As concerns the transfer of nociceptive information to the brain, several pathways other than the classical spinothalamic tract are of importance: for example, the postsynaptic dorsal column pathway. In discussing the roles of supraspinal structures in pain sensation, differences between its 'discriminative-sensory' and 'affective cognitive' dimensions should be emphasized. The purpose of the present article is to provide a global account of mechanisms involved in the induction of pain. Particular attention is focused on cellular aspects and on the consequences of peripheral nerve injury. In the first part of the review, neuronal pathways for the transmission of nociceptive information from peripheral nerve terminals to the dorsal horn, and therefrom to higher centres, are outlined. This neuronal framework is then exploited for a consideration of peripheral, spinal and supraspinal mechanisms involved in the induction of pain by stimulation of peripheral nociceptors, by peripheral nerve injury and by damage to the CNS itself. Finally, a hypothesis is forwarded that neurotrophins may play an important role in central, adaptive mechanisms modulating nociception. An improved understanding of the origins of pain should facilitate the development of novel strategies for its more effective treatment. PMID- 9987805 TI - Learning-induced physiological plasticity in the thalamo-cortical sensory systems: a critical evaluation of receptive field plasticity, map changes and their potential mechanisms. AB - The goal of this review is to give a detailed description of the main results obtained in the field of learning-induced plasticity. The review is focused on receptive field and map changes observed in the auditory, somatosensory and visual thalamo-cortical system as a result of an associative training performed in waking animals. Receptive field (RF) plasticity, 2DG and map changes obtained in the auditory and somatosensory system are reviewed. In the visual system, as there is no RF and map analysis during learning per se, the evidence presented are from increased neuronal responsiveness, and from the effects of perceptual learning in human and non human primates. Across sensory modalities, the re tuning of neurons to a significant stimulus or map reorganizations in favour of the significant stimuli were observed at the thalamic and/or cortical level. The analysis of the literature in each sensory modality indicates that relationships between learning-induced sensory plasticity and behavioural performance can, or cannot, be found depending on the tasks that were used. The involvement (i) of Hebbian synaptic plasticity in the described neuronal changes and (ii) of neuromodulators as "gating" factors of the neuronal changes, is evaluated. The weakness of the Hebbian schema to explain learning-induced changes and the need to better define what the word "learning" means are stressed. It is suggested that future research should focus on the dynamic of information processing in sensory systems, and the concept of "effective connectivity" should be useful in that matter. PMID- 9987806 TI - Synapse formation molecules in muscle and autonomic ganglia: the dual constraint hypothesis. AB - In 1970 it was thought that if the motor-nerve supply to a muscle was interrupted and then allowed to regenerate into the muscle, motor-synaptic terminals most often formed presynaptic specializations at random positions over the surface of the constituent muscle fibres, so that the original spatial pattern of synapses was not restored. However, in the early 1970s a systematic series of experiments were carried out showing that if injury to muscles was avoided then either reinnervation or cross-reinnervation reconstituted the pattern of synapses on the muscle fibres according to an analysis using the combined techniques of electrophysiology, electronmicroscopy and histology on the muscles. It was thus shown that motor-synaptic terminals are uniquely restored to their original synaptic positions. This led to the concept of the synaptic site, defined as that region on a muscle fibre that contains molecules for triggering synaptic terminal formation. However, nerves in developing muscles were found to form connections at random positions on the surface of the very short muscle cells, indicating that these molecules are not generated by the muscle but imprinted by the nerves themselves; growth in length of the cells on either side of the imprint creates the mature synaptic site in the approximate middle of the muscle fibres. This process is accompanied at first by the differentiation of an excess number of terminals at the synaptic site, and then the elimination of all but one of the terminals. In the succeeding 25 years, identification of the synaptic site molecules has been a major task of molecular neurobiology. This review presents an historical account of the developments this century of the idea that synaptic site formation molecules exist in muscle. The properties that these molecules must possess if they are to guide the differentiation and elimination of synaptic terminals is considered in the context of a quantitative model of this process termed the dual-constraint hypothesis. It is suggested that the molecules agrin, ARIA, MuSK and S-laminin have suitable properties according to the dual constraint hypothesis to subserve this purpose. The extent to which there is evidence for similar molecules at neuronal synapses such as those in autonomic ganglia is also considered. PMID- 9987807 TI - Using analog baselines to assess the effects of naltrexone on self-injurious behavior. AB - Naltrexone (NLTX), an opiate receptor antagonist, has been prescribed as a pharmacological intervention for the treatment of self-injurious behavior (SIB). Previous research has investigated NLTX's effects in the absence of information about the role of environmental events related to SIB. This study extended previous analyses by administering NLTX on analog baselines using a double-blind, placebo-controlled reversal design. Pretreatment functional analysis results showed that the SIB of the two participants occurred in more that one assessment condition. For one participant NLTX produced slight reductions in SIB across baseline conditions. The second participant's results showed that NLTX reduced head-slapping occurring during demand sessions, but had no apparent effect on head-banging occurring during alone and demand sessions. These outcomes suggest that NLTX may have function- and/or response-specific treatment effects. The potential utility of this model as a general method for assessing pharmacological interventions, as well as other implications and limitations, are discussed. PMID- 9987808 TI - Cessation of long-term naltrexone administration: longitudinal follow-ups. AB - Longitudinal follow-ups of the cessation of long-term Naltrexone administration (1 year of drug therapy) were conducted with a young woman (in her early 30s) with profound mental retardation who had previously displayed dramatic decreases in her self-injurious behaviors (SIB) both during, and for a period of at least 6 months following termination of drug treatment. After 2 and 4 years, post Naltrexone therapy, the subject continued to exhibit near-zero rates of SIB episodes despite significant turnovers in her direct care staff by the 2-year follow-up, and changes in her physical/living environment and fellow residents by 4-year follow-up. These findings provide further support to the idea that long term Naltrexone administration may result in highly durable reductions in SIB long after treatment ends and argue against certain aspects of the subject's environment affecting her rates of SIB significantly. These results are discussed in light of the endogenous opiate system theories of SIB. A functional analysis and discussion of the effectiveness of behavioral treatments for her few remaining SIB episodes are also provided. PMID- 9987809 TI - Acquisition of incidental information during instruction for a response-chain skill. AB - We examined the acquisition of incidental information and observational learning of incidental information by adolescents with moderate intellectual disabilities during school-directed systematic instruction. Effectiveness of constant time delay instruction for vocational-skill acquisition was evaluated within a multiple-probe design across six dyads. Dyadic instructional arrangements allowed the assessment of incidental information acquired through observation. The constant time-delay procedure was effective in teaching the target vocational skill. In addition, participants acquired and retained approximately 50% of the incidental information to which they were exposed during the consequent events of constant time-delay instruction either through direct verbal presentation or through observation of their peers' instruction. PMID- 9987810 TI - On the effects of "quality" of attention in the functional analysis of destructive behavior. AB - Two young children with mental retardation displayed inconclusive patterns of destructive behavior when a functional analysis was conducted using the procedures described by Iwata et al. (1982/1994). A second functional analysis incorporated modifications to the social attention condition that were based on interview data from care providers and descriptive observations. Results of the modified social attention condition indicated that a specific "quality" of attention was needed to identify the maintaining contingency for destructive behavior within an experimental analysis. Results are discussed in terms of considerations for further assessment when traditional analog functional analysis conditions are ineffective in isolating maintaining contingencies for destructive behavior. PMID- 9987811 TI - The effects of pictorial versus tangible stimuli in stimulus-preference assessments. AB - Recent research in the area of stimulus-preference assessment has progressively improved the accuracy and efficiency of this technology for predicting reinforcer potency. One way to potentially improve the efficiency of the procedure might be to use pictorial representations of stimuli in the assessment rather than the stimuli themselves. To determine the feasibility of using pictorial stimuli in preference assessments, multiple-stimulus preference assessments were conducted with two adults diagnosed with mental retardation using both tangible stimuli and pictorial cards representing these same stimuli. The tangibles stimulus assessment produced greater variations in selection percentages than the pictorial assessment. Subsequent reinforcer assessments confirmed that stimuli predicted by the tangibles assessment were more potent reinforcers than those predicted by the pictorial assessment. The results are discussed in the context of improving stimulus-preference assessment technology. PMID- 9987812 TI - Within-session patterns of responding during functional analyses: the role of establishing operations in clarifying behavioral function. AB - Functional analysis procedures have been demonstrated to be effective for identifying the operant mechanisms underlying problem behavior. However, functional analyses sometimes yield results that are undifferentiated (i.e., show similar levels of responding across test conditions). Within-session (i.e., minute-by-minute) analyses of response patterns during undifferentiated functional analyses have proven useful in clarifying behavioral function. This study extends previous research by examining within-session changes in responding associated with variations in relevant establishing operations. Levels of problem behavior during the presentation and removal of reinforcement were compared when responding occurred in test conditions associated with sources of social reinforcement (i.e., access to attention, materials, escape). Results showed that changes in responding associated with changes in relevant establishing operations could be examined to clarify behavioral function. PMID- 9987813 TI - Animal waste: risk of zoonotic parasite transmission. PMID- 9987814 TI - Legionella infection and control in occupational and environmental health. AB - This review describes the microbiological characteristics of Legionella species, their habits in the environment, source and route of infection, pathogenesis, symptoms and treatment of legionellosis, and disease outbreaks worldwide. We also describe prevention measures to deal with this organism in the work environment. Particularly in Japan, the present measures and countermeasures against legionellosis are inadequate when compared with those Europe and the United States because occupational and environmental medicine in Japan has not been structured from a microbiological viewpoint. As a result, workplace inspections have not covered cooling towers. We surveyed the cooling towers provided in work environments and in hospitals in Kitakyushu City for contamination by Legionella species. The surveillance definitely revealed that we are surrounded by cooling towers contaminated with Legionella. We conclude that in Japan, occupational and environmental physicians should routinely monitor the water in cooling towers. PMID- 9987815 TI - A multi-purpose system for water purification and sea-water softening. AB - A novel technique that can be used for reacting toxic carbon dioxide (CO2) emissions from power plants and other combustion wastes with sea water is described. A chemical interaction between CO2 and the cations in sea water, with the pH electrolytically regulated, can precipitate almost all the calcium and magnesium ions, as well as some sodium and potassium ions, as carbonates and bicarbonates. The carbonates and bicarbonates thus prepared can then be mixed with ash to yield a building material. Sulfur ions will be neutralized with calcium and magnesium, and the remaining ions can be removed using reverse osmosis or some other method. The technology and equipment for purification are based on modules that can be used for industrial waste-water, sea water, solutions, and otherwise. The module for separation of sand and suspended coarse substances consists of a tank for flocculation, coagulation, and precipitation of solid particles; and a low-pressure hydrocyclone. The module for purification from oil and fine suspensions is based on column flotation, flotation with a special ejector, and adhesion flotation. The module for ions and colloids consists of an absorbing filter with zeolite, fly ash, and other absorbing materials. Using a laboratory model consisting of a special mini-plant, we processed 10 L of factory-waste water containing more than 20 g/L organic content (compare with the upper limit of 0.02 g/L allowed by the Ministry of Environmental Protection in Israel). After the experimental solution was treated and evaporated to a small bulk, the water obtained was almost clear. On the basis of the results in the model, we present a scaled-up process for the design, development, and production of equipment for and the assembly of a large installation for drainage and water purification. PMID- 9987816 TI - Environmental exposure to tremolite asbestos: pleural mesothelioma in two Turkish workers in Germany. AB - This report concerns two Turkish immigrant workers, aged 50 and 59, who developed histologically confirmed diffuse malignant mesothelioma in the absence of obvious occupational exposure to asbestos in Germany. Both patients had spent their childhood in central Anatolia, Turkey, where the presence of tremolite asbestos in the environment has been described. In both patients, the lung-dust burden showed a high concentration of amphibole fibers (186 x 10(6) resp. 59 x 10(6) per gram dry tissue), mainly classified as actionolite/tremolite fibers in scanning transmission electron microscopy. In both patients, the disease was thus attributed to early environmental exposure to tremolite asbestos. PMID- 9987817 TI - Variations in 6-sulphatoxymelatonin excretion and oral temperature under a 12 hour shiftwork environment. AB - The aim of the present study was to follow the time-of-day variations in oral temperature and the excretion of a melatonin metabolite, 6-sulphatoxymelatonin (aMT6s), in individuals working fast-rotating, 12-h day and night shifts in a thermoelectric power station. Twenty-three male operators working on a 12-h-shift system (two successive days of the same shift: 0700-1900; 1900-0700, followed by two days off) were investigated. Oral temperature and aMT6s were measured at 4-h intervals on the second day shift and on the first and second night shifts. Clearly expressed "peaks" and "troughs" in aMT6s excretion and in oral temperature were found, indicating that a typical diurnal pattern of variation was preserved during fast-rotating, 12-h-shift work. The differences between the first and the second night shift in the examined parameters, particularly in aMT6s, can be attributed to the changes in sleep time between the two work shifts. PMID- 9987818 TI - Uncoupling of sequential heteromorphic developmental programs. AB - The regulatory basis for differences among species in the developmental rate at which successive life stages are reached ("heterochrony") is a subject of much controversy among vertebrate and invertebrate developmental biologists. The heterochrony in development of different insect species is characterized in part by the intercalcation between the embryo and adult of a (varied) number of heteromorphic larval instars. These heteromorphic larval instars exhibit changes of body form from one larval instar to the next, prior to the final metamorphic molt to the pupal form. The intractability of larval heteromorphosis to experimental dissection is due in part to the lack of suitable experimental probes that can test the nature of the coupling of each heterochronically expressed instar-specific program. The epistatic basis of expression of heteromorphic developmental programs was assessed by two-dimensional electrophoretic analysis of hemolymph proteins during the normal and experimentally manipulated feeding stages of the 3rd, 4th, and 5th (final) instar larvae, and during the prepupal stage, of Trichoplusia ni. Of the several hundred protein spots tracked, some were identified that were uniquely detected during a single stage, while others were observed during combinations of certain stages. The nature of coupling of sequential heterochronic expression of these proteins during successive instars or stages was tested by use of a parasite (Chelonus sp.) that injects regulatory material into the host embryo that later causes the subsequent precocious expression of the final instar larval program. Following the expression of a normal 3rd instar pattern, such larvae were observed to omit expression of the 4th instar program, including omission of the proteins heteromorphically specific to that instar, and instead then express an essentially normal final instar pattern. Thus, normal expression of the final instar feeding stage pattern was not invariantly coupled to prior expression of the penultimate instar-specific proteins or pattern. Also, expression of the full program of the final instar feeding stage was epistatic to teh penultimate instar program, i.e., the protein pattern unique to the penultimate larval instar was not co-expressed with the precociously expressed final instar pattern. Larvae developmentally redirected in this manner failed to fully express the final instar prepupal stage pattern of protein expression, due at least in part to failed expression of prepupal ecdysteroids, but this was shown not to arise from omission of any of the first 4 larval instars per se. The nature of the redirections in host development caused by this parasite finally provides means of probing the coupling of successive expression on heteromorphic programs during larval development. PMID- 9987819 TI - Cloning and expression of a gene encoding a Campoletis sonorensis polydnavirus structural protein. AB - Polydnaviruses are the only known group of mutualistic viruses. They are required for successful parasitization in many braconid and ichneumonid parasitoids. The intimacy of this mutualistic association is indicated by the integration and vertical transmission of polydnaviruses in wasp genomes and by their asymptomatic, developmentally regulated replication. The evolution of this mutualism raises several interesting issues that require a better understanding of the viral genome and viral replication. To develop probes for virus replication and morphogenesis, we have begun to characterize several viral structural proteins. A 699 bp cDNA encoding the p12 viral structural protein was cloned and sequenced. The p12 gene localizes to viral segment Y and encodes a predicted protein of 92 amino acids that does not encode a signal peptide and is unrelated to known peptide or nucleic acid sequences. The p12 mRNA is detected at the onset of virus replication. mRNA titers increase with increasing rates of virus replication. Polyclonal antisera raised against histidine-tagged p12 protein expressed in bacteria reacted specifically with the p12 polypeptide in Western blots of CsPDV virions. The p12 polypeptide was not detected in non replicative wasp or lepidopteran tissues by Western blot analyses but was readily detected in protein extracts of wasp ovaries. The data indicate that the p12 gene is a viral gene encoding a virion protein and provides a specific probe for virus replication that will be useful for studying the evolution of this group of mutualistic viruses. PMID- 9987820 TI - Plasmatocyte spreading peptide does not induce Microplitis demolitor polydnavirus infected plasmatocytes to spread on foreign surfaces. AB - Capsule formation by the moth Pseudopulsia includens requires that plasmatocytes change from being nonadhesive cells in circulation to strongly adhesive cells capable of attaching to the foreign target and one another. This change in adhesive state is induced by Plasmatocyte Spreading Peptide (PSP1); a 23 amino acid peptide isolated from P. includens plasma. Plasmatocytes from hosts parasitized by Microplitis demolitor remain in a nonadhesive state after infection by Microplitis demolitor polydnavirus (MdPDV). This alteration in plasmatocyte function prevents P. includens from encapsulating the developing parasitoid. In the current study, we examined whether MdPDV infection eliminates PSP1-responsive plasmatocytes from circulation or disrupts the ability of PSP1 to induce adhesion and spreading of plasmatocytes to foreign surfaces. In vivo experiments revealed that infection of P. includens by MdPDV induced an increase in the total number of hemocytes in circulation but reduced the proportion of hemocytes in circulation that were plasmatocytes. However, plasmatocytes normally capable of responding to PSP1 were not eliminated from circulation. Both in vivo and in vitro experiments indicated that plasmatocytes inoculated with MdPDV lost the capacity to respond to PSP1 4-6 h post-infection. Infection of P. includens with MdPDV reduced expression levels of prepro-PSP1 mRNA in hemocytes but did not appear to alter expression levels in fat body. PMID- 9987821 TI - Total synthesis and biological activity of lactacystin, omuralide and analogs. AB - Lactacystin (1) and the related beta-lactone omuralide (2) are remarkably selective and potent irreversible inhibitors of the 20 S proteasome, a large polymolecular protein machine which is responsible for the degradation of ubiquitin-labeled proteins. Because of this fact 1 and 2 have emerged as important tools in biochemistry and cell biology. The challenge of synthesis has been accepted by several research groups with the result that 1 and 2 and their analogs can now be synthesized by a variety of synthetic approaches. This review summarizes the synthetic processes which have been developed to date for the production of such compounds. The study of biological activity of analogs of 1 and 2 has clearly defined the structural features which are responsible for the potency of 1 and 2, as described in the closing section of this account. It is concluded that 1 and 2 are nearly optimal for the irreversible inactivation of the 20 S proteasome. PMID- 9987822 TI - Peptide based interleukin-1 beta converting enzyme (ICE) inhibitors: synthesis, structure activity relationships and crystallographic study of the ICE-inhibitor complex. AB - Based on the X-ray structure of the complex of Ac-Tyr-Val-Ala-Asp-H (L-709049) and interleukin-1 beta converting enzyme (ICE), we synthesized compounds which were derived from 2-NapCO-Val-Pro-Asp-CH2OPh (1) to obtain a potent inhibitor in the cell assay. Among these compounds, (3S)-N-methanesulfonyl-3-[[1-[N-(2 naphthoyl)-L-valyl]-L-prolyl]amino]- 4-oxobutanamide (27c) showed high potency not only in the enzyme assay but also cell assay with IC50 values of 38 nM and 0.23 microM, respectively. Compound 27c, with a c log P value of 1.76, had a more hydrophilic character compared with 1. Compound 27c also dose dependently inhibited LPS-primed ATP-induced IL-1 beta release in mice. The crystal structure of the complex of compound 27c and ICE revealed that compound 27c had further interactions with ICE in the naphthoyl group at the P4 position and in the methyl group of the methanesulfonamidecarbonyl group at the P1 position, compared with L 709049. To our knowledge, compound 27c is the first example that shows a strong inhibitory activity without the carboxyl group at the P1 position. PMID- 9987823 TI - Synthesis and muscarinic activity of novel aniline derivatives with a 1 azabicyclo[3.3.0]octane moiety. AB - In order to develop drugs effective against Alzheimer's disease, we synthesized a series of aniline derivatives having a characteristic cyclic amine, 1 azabicyclo[3.3.0]octane ring, and evaluated their binding affinity for the central muscarinic cholinergic receptor. Among these compounds which showed high affinity to the M1 receptor, N-[2-(1-Azabicyclo[3.3.0]octan-5-yl)ethyl]-2 nitroaniline (9f fumarate, SK-946) showed the highest affinity. The ability of this compound to improve cognitive function was assessed using the passive avoidance test in scopolamine-induced dementia mice. Some anilines with a 1 azabicyclo[3.3.1]nonane ring were also synthesized by the ring expansion of the 1 azabicyclo[3.3.0]octane ring, and showed a high affinity for the central muscarinic cholinergic receptor. PMID- 9987824 TI - Synthesis and nematocidal activity of diarylnonanoids related to malabaricones. AB - Twenty diarylnonanones were synthesized and their nematocidal activity was examined. Among those, the p-hydroxy compound 16 exhibited the strongest activity comparable to the natural diarylnonanoids, malabaricones A and C. Diarylundecanoid 57 also showed appreciable activity. PMID- 9987825 TI - Effects of removal of stratum corneum, delipidization and addition of enhancers, ethanol and l-menthol, on skin permeation of benzoic acid and its 4-n-alkyl substituents in excised guinea pig dorsal skin. AB - Skin penetration of benzoic acid and its 4-alkyl substituents (methyl, ethyl, n propyl and n-butyl) through excised guinea pig dorsal skin was examined, and effects of removal of stratum corneum, delipidization and addition of the penetration enhancers, ethanol and l-menthol plus ethanol, were observed. Permeability coefficients, which increased with the increase in their alkyl chain lengths, depended on the ratio of undissociated form of the derivatives. Removal of stratum corneum by tape stripping and delipidization by a chloroform-methanol mixture, whose effects on the permeation were similar, increased the permeability coefficients of the derivatives, especially those of relatively hydrophilic derivatives. Addition of 1% l-menthol plus 15% ethanol increased the permeability coefficient of benzoic acid, but decreased those of ethyl-, n-propyl- and n-butyl substituents, and differences in the permeability coefficients among these acids almost disappeared. A similar though weaker tendency was observed for the effects of 15% ethanol itself. Analysis of transfer free energy of the methylene group from vehicle to skin revealed that tape stripping and delipidization induced the reduction of lipophilic barrier property, although it still remained after these treatments. The analysis also showed that the addition of the enhancers made the skin relatively more hydrophilic compared to the vehicle, which induced an increase in permeability coefficient of benzoic acid and decreases in those of its lipophilic substituents. PMID- 9987826 TI - Synthetic inhibitors of DNA topoisomerase I and II. AB - A new type of synthetic inhibitor of DNA topoisomerase I and II was examined and several of these derivatives exhibited strong dual activity against these enzymes. This series of compounds showed high cytotoxic activities against cancer cells, but only a limited number of compounds showed any noticeable activity in an in vivo test against murine P388. Non-specific toxicity was observed in the in vivo tests. PMID- 9987827 TI - Preparation of lecithin microcapsules by a dilution method using the Wurster process for intraarterial administration in gadolinium neutron capture therapy. AB - Lecithin microcapsules containing gadolinium (Gd) were designed and prepared as a dosage form for intraarterial administration to accumulate Gd in tumors in neutron capture therapy. The microcapsules were composed of 1) a lactose core, 2) a layer of distearylamide of gadopentetic acid (Gd-DTPA-SAm) and polyvinylpyrrolidone (PVP) with or without soybean lecithin (SL) and 3) a membrane containing SL, cholesterol, stearic acid and PVP at three different compositions. A dilution method using the Wurster process was developed for small scale preparation. In spite of using only 2 g of Gd-DTPA-SAm each, three types of microcapsules were obtained with a content of 24.9% as Gd-DTPA-SAm (3.66% as Gd) even at 150% coating level. The swelling type of microcapsules (MC-D1) did not release Gd at all for the entire 120 min of the experiment in a 0.9% saline solution. On the other hand, the rapid-erosion type (MC-D2) and the vesicle dispersing type (MC-D3) released Gd with a lag time. The percent released depended on the coating level and the SL content in the Gd-fixing layer. A large number of droplet-like particles spouted out, and/or tubular vesicles formed with MC-D2 and MC-D3 in the saline solution. These phenomena implied that the water insoluble Gd-DTPA-SAm would be entrapped in these particles/vesicles. When MC-D2 and MC-D3 were administered to normal rats via the hepatic artery, a Gd accumulation as high as 70 and 71% of the injected dose was detected in the whole liver 2 h after administration. In addition, biochemical and histological evaluation of the liver after administration indicated that embolization of the microcapsules actually occurred in the blood vessels, and that necrosis induced by ischemia was not serious. These results suggested that administration of these microcapsules might be multiply repeated in order to accumulate the required amount of Gd in tumors. PMID- 9987828 TI - Immunomodulatory constituents from three ascomycetes, Gelasinospora heterospora, G. multiforis, and G. longispora. AB - Three new 2-pyrones (2H-pyran-2-ones) called multiforisins G (3), H (1), and I (4), and a known hexaketide sordarial (2) have been isolated from an Ascomycete Gelasinospora heterospora. Among them, 1, 2, and 3 have been proved to be the immunosuppressive components of the fungus. Compounds 1, 3, and 4 have also been isolated from G. multiforis together with multiforisin A (5), which was formerly isolated from this fungus as its main immunosuppressive feature, and 1-5 have also been isolated from G. longispora. The absolute stereostructure of 2, which was not previously certain, has finally been determined to be (3'R,4'S). It has been found that the multiforisins 1, 3, and 5 in which one of the two substituents at positions 3 and 5 is a hydroxymethyl group and the other is a formyl or an acetoxymethyl group, show high immunosuppressive activity; the immunosuppressive activity of 3 does not seem to be due to inhibition of interleukin 2 (IL-2) production. PMID- 9987829 TI - Synthesis and evaluation of novel coumarin-based esterase-sensitive cyclic prodrugs of peptidomimetic RGD analogs with improved membrane permeability. AB - Earlier, we reported the development of a coumarin-based prodrug system that could be used for the preparation of cyclic prodrugs of opioid peptides. These cyclic prodrugs exhibited excellent membrane permeability characteristics. Therefore, it was of interest to determine the effects of this prodrug strategy on the membrane permeabilities of peptidomimetics which also have low membrane permeabilities. For this study, we have chosen two RGD (Arg-Gly-Asp) peptidomimetics, which have the potentials to be developed clinically as orally active antithrombotic agents. However, the clinical development of oral dosage forms of these RGD analogs has been hindered by their low intestinal mucosal permeability. Therefore, we have synthesized the corresponding coumarin-based cyclic prodrugs of these RGD peptidomimetics, which have the two most polar functional groups, a carboxyl and an amino group, masked as an ester and an amide, respectively. These cyclic prodrugs were shown to have higher membrane interaction potentials, as estimated by their partitioning between aqueous buffer and an immobilized artificial membrane, than the corresponding RGD analogs suggesting that they should exhibit good membrane permeation characteristics. Subsequently, in a separate study these cyclic prodrugs were shown to be 5 to 6 fold more able to permeate monolayers of Caco-2 cells, an in vitro cell culture model of the intestinal mucosa barrier, than the corresponding RGD peptidomimetics. PMID- 9987830 TI - Antiproliferative constituents from umbelliferae plants. V. A new furanocoumarin and falcarindiol furanocoumarin ethers from the root of Angelica japonica. AB - The CHCl3 extract of the root of Angelica japonica showed high inhibitory activity against human gastric adenocarcinoma (MK-1) cell growth. From this extract, a new furanocoumarin named japoangelone and four furanocoumarin ethers of falcarindiol, named japoangelols A-D, were isolated together with caffeic acid methyl ester, four polyacetylenic compounds (panaxynol, falcarindiol, 8-O acetylfalcarindiol, and (9Z)-1,9-heptadecadiene-4,6-diyne-3,8,11-triol), eight coumarins (osthol, isoimperatorin, scopoletin, byakangelicin, xanthotoxin, bergapten, oxypeucedanin methanolate, and oxypeucedanin hydrate), and two chromones (3'-O-acetylhamaudol, and hamaudol). The structures of the new isolates were determined based on spectral evidence. The ED50 of isolates against MK-1, HeLa, and B16F10 cell lines are reported. PMID- 9987831 TI - Simultaneous analysis of genes by capillary electrophoresis with a laser-induced fluorescence detector using a stepwise field strength gradient. AB - A mixture of polymerase chain reaction (PCR) products, 100, 105, 300, 310, 485, and 500 base pair (bp) DNA fragments, was analyzed by capillary electrophoresis equipped with a laser-induced fluorescence detector (CE-LIF) using a stepwise gradient of electric field strength. The optimum condition for the analysis of PCR products was 0.5% methylcellulose and 160 V/cm from 0 to 10 min and 270 V/cm from 10 to 17 min. The length (bp) of DNA could be estimated from the relationship between the relative migration time and bp length. The relative standard deviation (R.S.D.) of DNA size (bp) was less than 3.5% and the difference from the true value was only 2.4 bp. PMID- 9987832 TI - Application of Schiff base copper(II) and iron(III) chelates to site-specific cleavage of a trypsin. AB - Amidine-containing Schiff base iron(III) and copper(II) chelates were prepared from alpha-amino acid, metal ion, and salicylaldehyde. These chelates behaved as specific inhibitors of trypsin, with Ki values in the range 10(-5)-10(-6) M. Selective cleavage of the trypsin backbone resulting from specific binding of the chelate to the trypsin active site was investigated. Cleavage was observed when trypsin was incubated with amidine-containing copper(II) or iron(III) chelate, H2O2, and ascorbate. Examination of the three-dimensional structure of trypsin suggests that cleavage occurred at a peptide bond within the Gly195-Ala204 sequence. PMID- 9987833 TI - Synthesis of the selective 5-hydroxytryptamine 4 (5-HT4) receptor agonist (+)-(S) 2-chloro-5-methoxy-4-[5-(2-piperidylmethyl)-1,2,4-oxadiazol-3-y l]aniline. AB - In a search for novel 5-hydroxytryptamine 4 (5-HT4) agonists focusing on the linker group of benzamide derivatives, 2-chloro-5-methoxy-4-[5-(2 piperidylmethyl)-1,2,4-oxadiazol-3-yl]a niline (2) was prepared and its optical isomers were separated. The S isomer 2(S) showed high affinity for the human 5 HT4 receptor without affinity for the human 5-HT3 receptor, and potent 5-HT4 agonistic activity in longitudinal muscle myenteric plexus (LMMP) preparations of guinea pig ileum. The R isomer 2(R) showed opposite selectivity. As a result of other receptor binding studies, 2(S) (YM-53389) was shown to be a highly selective 5-HT4 agonist. PMID- 9987834 TI - Studies of the chemical structure of gangliosides in deer antler, Cervus nippon. AB - The biological activity of deer antler has been considered to originate in the gangliosides, although the structures of gangliosides have not been well elucidated. The quality of deer antler as an Asian folk medicine has often been evaluated by the amount of gangliosides contained in the crude drug. We have completed the structural determination of five gangliosides isolated from deer antler in the present study. Five ganglioside fractions were isolated and purified from deer antler, Cervus nippon, by the Folch-Suzuki partition method, DEAE-Sephadex A-25, and further by silica gel column chromatography. High field proton nuclear magnetic resonance spectroscopy, gas chromatography/mass spectrometry, and fast atom bombardment-mass spectrometry studies characterized the isolated ganglioside fractions. GM3 and GD3 were present in the isolated ganglioside fractions. Samples were hydrolyzed in trifluoroacetic acid for direct compositional analysis and analyzed for sialic acid and neutral sugar without prior derivatization. Separation of the monosaccharides was achieved by HPLC on a Dionex CarboPac column eluted at a high pH. The resolved monosaccharides were identified using standard monosaccharides by pulsed amperometric detection. N Acetyl GM3 (Neu5Ac), N-glycolyl GM3 (Neu5Gc), and N-acetyl GD3 (Neu5Ac) were present in the antler. The major ceramide moiety was composed of C16:0 or C22:0 fatty acids along with either C18 sphingosine or C20 eicosasphingosine. PMID- 9987835 TI - Different inhibitory effects of 5-S-glutathionyl-beta-alanyl-L-dopa (5-S-GA-L-D) analogues on autophosphorylation and substrate phosphorylation of Src protein tyrosine kinase. AB - Starting with 5-S-glutathionyl-beta-alanyl-L-dopa (1) and 5-S-glutathionyl-beta alanyl-dopamine (2), a series of analogues with truncated glutathionyl and beta alanyl-dopa moieties were synthesized, and their inhibitory effects on autophosphorylation and substrate phosphorylation reaction by c-Src and by epidermal growth factor receptor (EGFR) were evaluated. When the glutamyl residue was removed, the inhibitory effects on v-Src autophosphorylation decreased about 4- to 5-fold, and concomitant removal of the glutamyl and beta-alanyl residues resulted in a 40- to 60-fold decrease in the inhibition of v-Src autophosphorylation. On the other hand, these modifications had little effect on the inhibitory activity of substrate (Raytide) phosphorylation by c-Src. Interestingly, 5-S-cysteinyl dopamine inhibited the Src substrate phosphorylation reaction with comparable potency to that of genistein. Nonpeptide lipophilic derivatives had a similar inhibition on v-Src autophosphorylation but decreased inhibitory effects on substrate phosphorylation when compared to the lead compounds. Most compounds showed little effect on substrate phosphorylation by EGFR. PMID- 9987836 TI - Biocontrol of plant disease: a (gram-) positive perspective. AB - Biological control offers an environmentally friendly alternative to the use of pesticides for controlling plant diseases. Unfortunately, growers continue to use chemical control over biological agents, and lack of knowledge often contributes to the downfall of a biocontrol agent. Knowledge of the biological environment in which the agent will be used and of how to produce a stable formulation are both critical to successful biocontrol. Certain Gram-positive bacteria have a natural formulation advantage over their Gram-negative counterparts: the spore. Although the Gram-positive bacteria have not been as well represented in the biocontrol literature, their spore-forming abilities and historical industrial uses bode well for biocontrol success. Here we describe several systems utilizing Gram positive biocontrol agents that have been researched in depth and provide models for the future of biocontrol. PMID- 9987837 TI - Characterisation of strain-specific sequences from an abortifacient strain of ovine Chlamydia psittaci using subtraction hybridisation. AB - Enzootic abortion in ewes (EAE) is caused by strains of Chlamydia psittaci which have the ability to invade and colonise the placenta of sheep. In an attempt to improve diagnostic methods for the detection of EAE, subtraction hybridisation was used to isolate unique fragments of the genome of an abortifacient strain (S26/3) of C. psittaci. One S26/3 strain-specific sequence identified was shown to encode a putative helicase which is repeated throughout the EAE genome. The labelled strain-specific helicase gene fragment was used in the dot-blot hybridisation test for the detection of EAE DNA in ovine placental samples. We report the identification of C. psittaci S26/3 strain-specific sequence with potential as diagnostic probes for the detection of EAE. PMID- 9987838 TI - Extensive proteolysis inhibits high-level production of eukaryal G protein coupled receptors in the archaeon Haloferax volcanii. AB - In this study the usage of the halophilic archaeon Haloferax volcanii as a production system for eukaryal G protein-coupled receptors (GPCRs) was characterized. The genes of four GPCRs were fused to the dihydrofolate reductase gene of H. volcanii. In Northern blots both 5' fragments and full-length fusion transcripts were found. In contrast, only C-terminal fusion protein fragments could be detected in Western blot analyses. Ligand binding experiments revealed that a minor amount of correctly folded human beta 2 adrenergic receptor was inserted into the membrane. The introduction of different modifications at the 5' and the 3' end of the receptor genes did not significantly increase the production level. Determination of the subcellular localization showed that fusion protein fragments containing one or more receptor helices were located in the membrane. The results indicate that neither transcription, translation nor membrane translocation but the activity of one or more proteases limits the level of GPCR production in H. volcanii. PMID- 9987839 TI - A consensus sequence for the Rhodospirillaceae SOS operators. AB - The sequences controlling the expression of the Rhodobacter capsulatus recA and uvrA genes belonging to the SOS DNA repair system have been identified by PCR mutagenesis. Data obtained demonstrated that the GTTCN7GTAC and GAACN7GAAC motifs present upstream of the recA gene and the GTTCN7GTTC motif found upstream of the uvrA gene are required for their respective DNA damage-mediated induction. Alignment of recA promoters of R. capsulatus, Rhodobacter sphaeroides and Rhodopseudomonas viridis with the uvrA promoters of R. capsulatus and R. sphaeroides has identified the consensus sequence GTTCVYVYTWTGTTC as the SOS operator site of the Rhodospirillaceae family. PMID- 9987840 TI - Digoxigenin-labeled probe for rapid identification of nisinogenic Lactococcus lactis strains. AB - From the nisZ gene sequence, a non-radioactive digoxigenin-labeled DNA probe, was tested for detection of nisin-producing strains using polymerase chain reaction amplification. The digoxigenin-labeled DNA probe clearly discriminated between nisin-producing and non-producing strains with a high degree of sensitivity and specificity. By agarose gel electrophoresis, 1.4 ng of nisin DNA was detected using the digoxigenin-labeled DNA probe compared with 11 ng using direct polymerase chain reaction amplification. A colony hybridization method using digoxigenin-labeled DNA to selectively detect nisinogenic bacteria showed that the nis-probe was specific and did not react with any other non-bacteriocinogenic and non-nisinogenic strains. PMID- 9987841 TI - Toxin-co-regulated pilus cluster in non-O1, non-toxigenic Vibrio cholerae: evidence of a third allele of pilin gene. AB - Polymerase chain reaction has been used to detect the presence of the virulence associated gene, tcpA and part of the promoter distal region of the toxin-co regulated pilus cluster in non-O1, non-toxigenic, Vibrio cholerae. The amplified regions were characterised by restriction fragment length polymorphism and heteroduplex motility assay. We describe the nucleotide sequence of the tcpA gene fragment from non-toxigenic vibrios from clinical and environmental sources. The present study shows that there are at least three types of the tcpA gene among V. cholerae and the primers specific for the classical tcpA gene, amplify all biotypes. A sequence similarity in other regions of the toxin-co-regulated pilus cluster is suggested. The evidences for the presence of this cluster among non toxigenic vibrios is, to our knowledge, reported for the first time. The use of restriction fragment length polymorphism for typing the tcpA and studying the alleles distribution is proposed. PMID- 9987842 TI - Differentiation of Lactococcus lactis subspecies lactis and subspecies cremoris strains by their adaptive response to stresses. AB - Lactococcus lactis subspecies lactis (L. lactis ssp. lactis) and Lactococcus lactis subspecies cremoris (L. lactis ssp. cremoris) were investigated in respect to their response to acid, bile-salt and freezing stresses. First, the sublethal and lethal levels of each stress were determined for both subspecies. For acid stress, the levels were pH 4.5 and 2.5, respectively, for L. lactis ssp. lactis, and pH 5.0 and 3.0, respectively, for L. lactis ssp. cremoris. For bile-salt stress, the levels were 0.03 and 0.1%, respectively, for L. lactis ssp. lactis, and 0.01 and 0.04%, respectively, for L. lactis ssp. cremoris. For freezing stress, 10 degrees C was used as the sublethal temperature and -20 degrees C was used as the lethal temperature for both subspecies. To evaluate the effect of each stress at log phase, a log-phase culture was challenged directly with the appropriate lethal level (control culture) and a second log-phase culture was pre exposed to the appropriate sublethal level prior to testing survival under normally lethal conditions (test culture). Some, if not most, of the cells were killed in the control cultures for all three stresses. However, in the test cultures, the viability was significantly improved for all of the L. lactis ssp. lactis strains tested, but not for the L. lactis ssp. cremoris strains. It appears, therefore, that L. lactis ssp. lactis is capable of displaying adaptive response to stresses, whereas L. lactis ssp. cremoris seems to lack this phenotype or the response is much weaker in this subspecies. The effect of each stress on stationary-phase cultures was also investigated. Unlike the log-phase cultures, the stationary-phase cultures of both subspecies, challenged directly with the lethal levels, were highly resistant to each of the three stresses tested. PMID- 9987843 TI - The mitochondrial genome of Mucor piriformis. AB - DNA was purified from the isolated mitochondria of a Mucor piriformis wild-type strain (NRRL 26211). A circular restriction map of the mitochondrial DNA was established on the basis of single and double digests with several restriction endonucleases. The average mitochondrial DNA size calculated from these data was 33.53 kbp; this is in good agreement with the contour length size (33.62 kbp) of the open circular molecules detected by electron microscopy. Heterologous hybridizations with cloned Aspergillus nidulans mitochondrial genes were used to locate some coding regions on the map. PMID- 9987844 TI - Patenting in biotechnology: a review of the 20th symposium of ECB8. AB - The patenting of biotechnological inventions is practically in harmony with the general requirements of patent protection. It stands still in the foreground of interests since this is the only technical field where the living material itself may be the subject matter of patents. In consequence ethical problems have arisen first of all in the patenting of human cells and genes in which there is no agreement between R&D firms, patent offices and green movements. This has called for the elaboration of special Directives. On the other hand, patent systems are instrumental in safeguarding biodiversity. This review gives a picture of the patenting situation in biotechnology in the European Patent Office and in Hungary, the host country of the Congress. It also gives practical advice to biotechnological researchers on how to draft the applications and to observe the time limits, as well as on the necessity and possibilities of the deposit of microorganisms. PMID- 9987845 TI - Lipophilic compounds in biotechnology--interactions with cells and technological problems. AB - Lipophilic compounds are of significant importance in modern biotechnology. Centerly of interest are the biodegradation as well as the biotransformation of such lipophilic and often water-immiscible substances. Both whole cells and/or enzymes are used for these processes. It is obvious that a wide range of problems arise in an application of such complex systems consisting of biocatalysts substrate(s), product(s), water, (in some cases water-immiscible organic solvents): (i) interactions between lipophilic compounds and the membranes resulting in the change of some physiological characteristics of the living system; (ii) problems in the transport of these compounds (substrates and/or products) within the complex structured reaction systems; (iii) the problem of increasing the solubility of the lipophilic and mostly water-immiscible compounds with a minimum of inhibition effects on the processes; (iv) the presence of lipophilic components may also cause changes of the transport processes within the system (e.g. immobilized cells) resulting in changed yield or activity of the biological system. These problems are critically discussed in this review in relation to the known modes of interaction of lipophilic compounds with membranes, the bioavailability of the substrates, and the cases of steroid biotransformations. An outlook of future aspects in research, development and application of such processes is given. PMID- 9987846 TI - Coimmobilization of glucoamylase and glucose isomerase by molecular deposition technique for one-step conversion of dextrin to fructose. AB - Glucose isomerase was immobilized by itself with adsorption and coimmobilized with glucoamylase by molecular deposition technique using macroporous trimethylamine polystyrene beads. Approximately 77.5% of the enzyme added was immobilized. The pH-activity curve of the immobilized glucose isomerase was broadened, resulting in 75% retention of its maximum activity at pH 6.2. The Km of the immobilized glucose isomerase was 1.28-fold that of the soluble one. When the two enzymes were immobilized together, the system was found capable of functioning at pH 6.0 to produce fructose from starch and dextrin. At this pH, the total fructose output of the coimmobilized enzyme system after 24 h was 1.9 times that of the free enzyme system. PMID- 9987847 TI - Activity of an Aspergillus terreus alpha-arabinofuranosidase on phenolic substituted oligosaccharides. AB - The effect of phenolic substitutions on the activity of an alpha arabinofuranosidase from Aspergillus terreus was investigated using feruloylated oligosaccharides isolated from plant cell walls, equivalent oligosaccharides obtained through treatment with specific ferulic acid esterases, and a synthetic lignin-carbohydrate complex (LCC). Feruloyl substituents limited the hydrolysis of arabinoxylan and arabinan oligosaccharides but only if the feruloyl group was esterified to the terminal non-reducing arabinose. Somewhat surprisingly, the LCC model compound, in which the arabinose residue is substituted with a bulky dilignol group, was degraded by the enzyme. This indicated that the enzyme is able to approach this linkage from the xylose side. PMID- 9987848 TI - Mating type-correlated molecular markers and demonstration of heterokaryosis in the phytopathogenic fungus Thanatephorus cucumeris (Rhizoctonia solani) AG 1-IC by AFLP DNA fingerprinting analysis. AB - The destructive soil-borne plant pathogenic basidiomycetous fungus Thanatephorus cucumeris (Frank) Donk [anamorph: Rhizoctonia solani Kuhn] is not a homogeneous species, but is composed of at least twelve anastomosis groups (AG), which seem to be genetically isolated. The genetics of several T. cucumeris anastomosis groups has been studied by analysis of heterokaryotic tuft formation in the area of contact between homokaryotic single-spore isolates, revealing that AG 1 is heterokaryotic and bipolar. To prove that tuft formation is due to heterokaryosis, AFLP DNA fingerprinting has been applied to a heterokaryotic T. cucumeris AG 1-IC isolate, its homokaryotic single spore-derived progeny, and newly formed heterokaryons. By means of AFLP markers, it is demonstrated that fluffy tufts formed upon pairing of homokaryons from different mating types are newly formed heterokaryons. Mating type-correlated markers have also been found, which will be useful for future studies of the genetics of this fungal species complex. PMID- 9987849 TI - Analysis of changes during subclone development and ageing of human antibody producing heterohybridoma cells by northern blot and flow cytometry. AB - The economic importance of obtaining high-producing subclones for large scale production of pharmaceutical proteins is self-evident. However, few papers have studied the changes that occur during subclone development. This information would be important for further improvement of screening and subcloning protocols. We have therefore compared subclones of a human-mouse heterohybridoma cell line producing a human antibody againt HIV-1. Three subclones with low, medium and high specific production rates were selected for this study and their light and heavy chain mRNA content, the intracellular content of light and heavy chain and the specific secretion rates compared. In addition the long time stability of antibody expression in the highest producing subclone was analysed for one year. For the three subclones a correlation between the intracellular content in light chain and the secretion rate was found, while the intracellular content in heavy chain was the same for all three subclones. These results indicate that the assembly in the endoplasmic reticulum (ER) is one of the major rate limiting factors in antibody production. During long time cultivation of the heterohybridoma cell line a continuous decrease in light and heavy chain production was seen without the appearance of a non producing sub-population. PMID- 9987850 TI - Concept design of computer-aided study on traditional Chinese drugs. AB - Traditional Chinese drugs (TCDs) have played a key role for Chinese people in the treatment of diseases since ancient times. The use of TCDs has generated a great amount of information in the past thousand years about the relationship between natural products and the human body. However, up to now, our understanding on the mode of action of the TCD is still limited. Considering that the basic mechanism of all drug function involves the interaction between the drug and biological receptors at the molecular level, we propose to connect TCDs with modern medicine theory through molecular structures. We propose to explain functions of TCDs by using the knowledge developed in modern molecular biology, pharmacology, computer chemistry, and biochemistry. We are working on a computer-aided Chinese drug study that is discussed in this paper. A short introduction on the progress of our research is also given. PMID- 9987851 TI - Application of nearest-neighbor and cluster analyses in pharmaceutical lead discovery. AB - High throughput screening (HTS) programs based on diverse collections of compounds can rapidly identify leads for potential drug candidates. In cases where the compound collection is truly diverse, one may only identify a few compounds of interest. However, where a large number of hits are identified, it becomes necessary to examine the structures to determine the true number of compound classes involved so that follow-up studies may be conducted as efficiently as possible. In this case, cluster analysis is applied to determine the structural relationship among HTS hits. To efficiently expand around the region of the hit (or a class of hits) in chemical space, we have applied nearest neighbors analysis to select additional compounds from collections of a large number of commercial vendors, achieving an average hit rate in excess of 15%. Applying these techniques in a number of different cases, we obtained results that are useful for subsequent investigations of hits from HTS and other relevant molecular structures from the literature. PMID- 9987852 TI - Quantitation of pyrethrum residues in brown tree snakes. AB - A reversed-phase solid-phase extraction-gas chromatography (SPE-GC)-electron capture detection method is developed to quantitate individual rethrin residues in pyrethrum-exposed brown tree snakes. Aliquots (6 g) of homogenized snake tissue are extracted with 10 mL acetonitrile. The rethrins are recovered from the acetonitrile extract and concentrated using C8 SPE. The rethrins are eluted from the SPE column with pentane, evaporated to near dryness, and reconstituted to 1 mL with 1-propanol. Individual rethrins are quantitated using GC analysis of the 1-propanol solution. Method limits of detection for rethrins range from 0.63 to 6.51 ng/g. The mean recovery for all rethrins is 70.8% with a standard deviation of 5.7%. This method is used to successfully quantitate incurred rethrin residues in pyrethrum-exposed brown tree snakes. PMID- 9987853 TI - Comparison of solid-phase microextraction and dynamic headspace methods for the gas chromatographic-mass spectrometric analysis of light-induced lipid oxidation products in milk. AB - A sensitive, rapid procedure for testing lipid oxidation products in milk is developed using solid-phase microextraction (SPME) and gas chromatography-mass spectrometry. SPME is as sensitive as dynamic headspace (DH) analysis for measuring the pentanal and hexanal produced in milk after exposure to light. Furthermore, compared with DH, SPME is less expensive and demonstrates better precision and accuracy. In addition, SPME does not exhibit carryover or septa artifact peaks. The linearity of calibration curves (based on the method of additions technique with an internal standard) is consistently better for SPME than for DH. Furthermore, replicate analyses of pentanal and hexanal spiked in skim milk and 2% milk at 2 ng/mL demonstrate significantly lower coefficients of variation using SPME. To further test the practicality of SPME for measuring light-induced chemical changes in milk, 2% milk and skim milk samples are exposed to fluorescent light (200 foot-candles) for 0, 3, 6, 9, 12, 17, 24, and 48 h and analyzed by SPME and DH. Pentanal and hexanal in all samples are measured by SPME and DH. Correlation coefficients of resulting plots indicate that SPME is more accurate than DH in measuring the quantity of lipid oxidation products in milk. PMID- 9987854 TI - Systematic nonlinearities in the perception of temporal intervals. AB - Rats judged time intervals in a choice procedure in which accuracy was maintained at approximately 75% correct. Sensitivity to time (d') was approximately constant for short durations 2.0-32.0 s with 1.0- or 2.0-s spacing between intervals (n = 5 in each group, Experiment 1), 2.0-50.0 s with 2.0-s spacing (n = 2, Experiment 1), and 0.1-2.0 s with 0.1- or 0.2-s spacing (n = 6 in each group, Experiment 2). However, systematic departures from average sensitivity were observed, with local maxima in sensitivity at approximately 0.3, 1.2, 10.0, 24.0, and 36.0 s. Such systematic departures from an approximately constant d' are predicted by a connectionist theory of time with multiple oscillators and may require a modification of the linear timing hypothesis of scalar timing theory. PMID- 9987855 TI - Posttraining shifts in the overshadowing stimulus-unconditioned stimulus interval alleviates the overshadowing deficit. AB - Two conditioned lick suppression experiments explored the effects on overshadowing of a posttraining change in the temporal relationship between the overshadowing conditioned stimulus (CS) and the unconditioned stimulus (US). Rats received either trace (Experiment 1) or delay (Experiment 2) overshadowing training. Then pairings of the overshadowing CS and US were given with either a trace or delay temporal relationship. Overshadowing was alleviated by shifting the overshadowing CS-US temporal relationship so that it no longer matched the overshadowed CS-US temporal relationship. These outcomes are explicable in terms of an integration of the comparator hypothesis, which states that cue competition effects (e.g., overshadowing) will be maximal when the information potentially conveyed by competing CSs is equivalent, and the temporal coding hypothesis, which states that CS-US intervals are part of the information encoded during conditioning. PMID- 9987856 TI - Palatability and foraging cost interact to control caloric intake. AB - The combined effects of meal cost and food flavor on meal size were studied with a method that avoided the covariation of nutrient composition and caloric density with palatability. As rats (Rattus norvegicus) drank flavored fluids (unpalatable 0.05% sucrose octaacetate [SOA], neutral 0.05% saccharin, and palatable 2% Polycose + 0.2% saccharin [P + S]), liquid diet was infused intragastrically. Relative to saccharin, rats with free access ate 10% more calories in larger meals while consuming P + S and initially ate fewer calories in smaller but more frequent meals while drinking SOA. Other rats lever-pressed to begin meals, which halved meal number and doubled meal size relative to the free-access group. Although foraging rats also ate larger P + S meals and smaller SOA meals, the changes did not affect total intake. Without the usual differential postingestive effects of foods that differ in palatability, making food more costly blunts rats' response to its flavor. PMID- 9987857 TI - Latent inhibition and perceptual learning in a swimming-pool navigation task. AB - In each of 3 experiments, rats were preexposed to the 4 distinct landmarks surrounding a circular pool before being trained to find a submerged platform located in a fixed position in the pool. When preexposure was to pairs of adjacent landmarks, it consistently retarded subsequent learning (a latent inhibition effect). When preexposure was to 1 landmark at a time, then, provided the 4 landmarks all contained a salient feature in common, preexposure facilitated subsequent learning (a perceptual learning effect). The results provide little support for the notion of a cognitive map and are quite consistent with an associative analysis. PMID- 9987858 TI - Blocked and overshadowed stimuli are weakened in their ability to serve as blockers and second-order reinforcers in Pavlovian fear conditioning. AB - The ability of a blocked or overshadowed conditioned stimulus (CS) to serve as (a) blocker or (b) a 2nd-order reinforcer in Pavlovian fear conditioning was tested in 152 albino rats. CS-evoked suppression of barpressing for food was the index of conditioned fear. Experiments 1 and 2 showed that an overshadowed CS was weakened in its ability to serve as a blocker. In Experiment 2, a blocked CS was similarly weakened. Experiment 3 showed that an overshadowed and blocked CS was weakened in its ability to serve as a 2nd-order reinforcer. Experiments 4 and 5 failed to restore the blocking ability of blocked (Experiment 4) or overshadowed (Experiment 5) CSs by extinguishing the CSs that had blocked or overshadowed them. Results favor a learning-deficit view of blocking and overshadowing. PMID- 9987859 TI - Memory for the content of caches by scrub jays (Aphelocoma coerulescens). AB - To test whether scrub jays (Aphelocoma coerulescens) remember the contents of food caches, in Experiment 1 birds cached peanuts and kibbles in two distinct caching trays and recovered them 4 or 172 hr later. The relative incentive value of the foods was manipulated by prefeeding one of the foods immediately before cache recovery. Birds preferentially searched for non-prefed food caches even when the caches had been pilfered prior to the recovery test. In Experiment 2, birds cached both foods in different sites within each tray, recovering peanuts from one tray and kibbles from the other tray 3 hr later. After prefeeding with one food, birds preferentially searched tray sites in which they had cached but not retrieved the non-prefed food. Thus jays remember the specific foods they cache and recover by a mnemonic process that cannot be explained in terms of simple associations between the foods and their cache locations. PMID- 9987860 TI - Role of a stimulus filling an action-outcome delay in human judgments of causal effectiveness. AB - Experiments examined the effect of a stimulus filling a response-outcome delay on human judgments of causal effectiveness. In Experiment 1, subjects rated the effectiveness of 2 concurrently available responses. One response led to the outcome with a 75% probability, the other never led to the outcome. Ratings were higher for the former compared to the latter key, and for immediate compared to delayed outcomes. A signal presented during the delay ameliorated this deficit. Experiments 2 and 3 examined conditioned reinforcement and perceptual catalysis accounts of this effect. In both experiments, 50% of responses on each of 2 keys led to an outcome. Ratings were high, relative to an unsignaled condition, when a stimulus filled the outcome delay, and when the same stimulus followed the response but did not precede the outcome. This result is not consistent with the operation of perceptual catalysis and was shown to be the result of secondary reinforcement-like processes rather than outcome-confusion or generalization between responses (Experiments 3, 4). PMID- 9987861 TI - Exploratory studies of inhibitory conditioning in honeybees (Apis mellifera). AB - The best available evidence of inhibitory conditioning in vertebrates comes from experiments in which variants of A+/AB- and A+/B- training were compared in terms of response to B in summation and retardation tests, the results suggesting that inhibition is generated by nonreinforcement as an increasing function of the excitatory value of the setting. We report here 7 experiments with foraging honeybees (Apis mellifera) that failed to show a difference in the effects of the 2 treatments. On the basis of previous experiments as well as supplementary experiments whose results give no reason to doubt the sensitivity of the training techniques and measures used, our consistently negative results may mean either that inhibition in honeybees is generated by nonreinforcement independently of the setting or that there is no inhibitory conditioning at all in honeybees--that the only associative function of nonreinforcement is to reduce excitatory strength. PMID- 9987862 TI - The randomization procedure in the study of categorization of multidimensional stimuli by pigeons. AB - Pigeons categorized rectangles varying in both height and width in an adaptation of a method used by Ashby and colleagues for the cognitive and neuropsychological analysis of human decision bounds for ill-defined categories. Optimal decision bounds were defined in a stimulus space in which the point (x,y) corresponded to a rectangle with width x and height y. Four tasks defined the following 4 optimal bounds: x = y, x = c, x = y + d, and (x-a)2 + (y-b)2 = r2, where a, b, c, d, and r were constants given by a task. Estimated decision bounds for individual pigeons conformed approximately to the optimal decision bound in each of the 4 tasks. The new method suggests a way to (a) integrate the disparate literature on ill-defined visual concepts and on optimal performances in nonhuman animals; (b) compare how humans and nonhuman animals categorize ambiguous, multidimensional configural stimuli; (c) model how nonhuman animals categorize naturalistic stimuli; and (d) infer that pigeons' categorizations of naturalistic stimuli may be remarkably close to optimal. PMID- 9987863 TI - Postmortem drug redistribution--human cases related to results in experimental animals. AB - Femoral blood is widely accepted as the most reliable postmortem specimen for drug analysis in forensic toxicology. There is considerable evidence that the drug concentrations in peripheral blood samples are closer to the antemortem level than the concentration in cardiac blood. In the present study drug concentrations measured in postmortem femoral and/or heart blood samples from eight cases were compared with the concentration found in serum samples from the same subject collected antemortem or perimortem. The drugs involved were amitriptyline, nortriptyline, imipramine, verapamil and chloroquine. Two additional cases with very early postmortem blood samples, as well as femoral blood samples from later autopsy, involved amphetamine and tetrahydrocannabinol. The results from the human cases were compared with results from rat experiments on similar drugs. The samples were analyzed by high performance liquid or gas chromatography. The cases with tricyclic antidepressants had a median postmortern femoral blood to antemortem serum drug concentration ratio of 3.3, the 95% reference range being from 1.1 to 6.0 (pooled data). Large variations of the ratios were seen. The extremes noted were a postmortem femoral blood to antemortem serum drug concentration ratio of 0.9 in a case with nortriptyline and 49 in the case with chloroquine. The low ratio in the former case could be due to attempted resuscitation, while the high ratio in the latter case is probably due to the extremely high apparent volume of distribution and a high blood to plasma concentration ratio for chloroquine. Accordingly, it is dubious whether the drug concentration found in femoral blood at autopsy can be accepted as being representative for the antemortem level. The results obtained from the human cases in the present study were generally in reasonable agreement with previous rat experiments, confirming that the animal studies when interpreted carefully, are indicative of the changes observed in man as well as a previous study in pigs. Studies on drug concentrations in pigs are not necessarily more representative for the findings in humans than experiments with a smaller animal like the rat. The postmortem concentration changes observed for tetrahydrocannabinol in man were found to be unpredictable, while in the accompanying experimental rat study there was a significant postmortem decrease in the tetrahydrocannabinol blood concentration measured in blood from the inferior vena cava. In special cases where the diagnosis of overdose is to be used as judicial evidence, a single sample of blood may prove insufficient. In such cases, analyses of several samples of blood and tissue will increase the possibility of reaching a correct conclusion, but reference values on drug concentrations in tissues are often missing. PMID- 9987864 TI - Redistribution of basic drugs into cardiac blood from surrounding tissues during early-stages postmortem. AB - The objective of this study was to elucidate the mechanism(s) responsible for increases in the concentrations of basic drugs in cardiac blood of bodies in a supine position during early-stages postmortem. The concentrations of basic drugs in cardiac blood and other fluids and tissues of three individuals who had used one or more basic drugs were examined. The results were compared with those obtained in experiments using rabbits. In the first case, autopsy of whom was performed approximately 12 h after death, methamphetamine was detected and its concentrations were in the order: lung >> pulmonary venous blood > blood in the left cardiac chambers (left cardiac blood) >> pulmonary arterial blood > blood in the right cardiac chambers (right cardiac blood). In the second case, autopsy of whom was performed approximately 9 h after death, methamphetamine and morphine were detected and their concentrations in the left cardiac blood were roughly twice those in the right cardiac blood. The methamphetamine and morphine concentrations in the lung were 2 to 4 times higher than those in cardiac blood samples. In the third case, autopsy of whom was performed approximately 2.5 days after death, the pulmonary veins and arteries were filled with chicken fat clots. Toxicological examination revealed the presence of four basic drugs: methamphetamine, amitriptyline, nortriptyline and promethazine. Their concentrations in the lung were 5 to 300 times higher than those in cardiac blood, but postmortem increases in the concentrations of these drugs in the cardiac blood were not observed. In the animal experiments, rabbits were given 5 mg/kg methamphetamine intravenously or 20 mg/kg amitriptyline subcutaneously and sacrificed 20 min or 1 h later, respectively. The carcasses were left in a supine position at the ambient temperature for 6 h after or without ligation of the large vessels around the heart. For the groups with ligated vessels, the mean ratios of the drug concentrations in both left and right cardiac blood samples 6 to 0 h postmortem were about 1, whereas in those without ligated vessels, these ratios were about 2 and 1, respectively. The order of the methamphetamine and amitriptyline concentrations in blood and tissue samples were roughly: lungs > myocardium and pulmonary venous blood > cardiac blood, inferior vena caval blood and liver. Our results demonstrate that when bodies are in a supine position, (1) basic drugs in the lungs diffuse rapidly postmortem into the left cardiac chambers via the pulmonary venous blood rather than simply diffusing across concentration gradients, and (2) basic drugs in the myocardium contribute little to the increases in their concentrations in cardiac blood during the early postmortem period. PMID- 9987865 TI - Metabolic production of amphetamine following administration of clobenzorex. AB - Many of the anorectic drugs that are metabolized to amphetamine and/or methamphetamine pose significant concerns in the interpretation of amphetamine positive drug testing results. One of these drugs--clobenzorex--has been shown to produce amphetamine. Thirty milligrams of clobenzorex hydrochloride, in the form of a single Asenlix capsule (Roussel, Mexico), were administered orally to five human volunteers with no history of amphetamine, methamphetamine or clobenzorex use. Following administration, urine samples (total void volume) were collected ad lib for seven days and pH, specific gravity and creatinine values were determined. To determine the excretion profile of amphetamine and parent drug, samples were extracted, derivatized, and analyzed by gas chromatography/mass spectrometry (GC/MS) using a standard amphetamine procedure with additional monitoring of ions at m/z 91, 118, 125 and 364 for the detection of clobenzorex. Peak concentrations of amphetamine were detected at 4 to 19 h postdose and ranged from approximately 715 to 2474 ng/mL amphetamine. Amphetamine could be detected (> 5 ng/mL) in the urine in one subject for up to 116 h postdose. GC/MS was also used to determine the enantiomeric composition of the metabolite, amphetamine. This analysis revealed the metabolically derived amphetamine was only the d enantiomer. This differs from previous literature which indicates clobenzorex is the racemic N-orthochlorobenzyl derivative of amphetamine. PMID- 9987866 TI - Methamphetamine as a risk factor for acute aortic dissection. AB - Acute aortic dissections are catastrophic vascular events that have a high rate of mortality. Aortic dissections have been associated with a variety of factors, particularly hypertension. We reviewed 84 medical examiner autopsies on individuals dying from acute aortic dissections with particular emphasis on the role of drugs. Previous case reports have associated aortic dissections with both cocaine and methamphetamine intoxication. We found that seven of the 35 cases tested for drugs of abuse were positive for methamphetamine. Our study had no cases of solely cocaine-related dissection, although one of the cases was positive for both methamphetamine and the cocaine metabolite benzoylecgonine. No significant association was found with any other drugs. As with other studies, we found the most common risk factor to be hypertension. Surprisingly, methamphetamine use was the second most common risk factor. The association between methamphetamine use and aortic dissection is most likely due to its hypertensive effect. Although methamphetamine appears to pose a greater risk than cocaine, both drugs should be considered as possible factors in all aortic dissections. PMID- 9987867 TI - Human methamphetamine-related fatalities in Taiwan during 1991-1996. AB - Methamphetamine (MAP) is currently considered to be the major illicit drug in Taiwan, and MAP constitutes the majority of illicit drugs seized by the judicial institutes. Thus, MAP has raised public attention. The purpose of this retrospective study is to observe the trends of MAP-related fatalities in Taiwan with respect to the manners of death so as to determine the epidemiological implications of MAP. Two hundred and forty-four MAP-related fatalities out of a total of 3958 forensic fatalities were collected by the Forensic Medicine Center (Taiwan) during the period of 1991 to 1996. The annual percentages of MAP-related fatalities compared to the total autopsy cases during 1991 through 1996 were 3.4, 10.3, 12.1, 4.2, 4.0 and 5.6%, showing that the number of MAP-related fatalities increased from 1991 to 1993, declined during 1994 and 1995, and rose again in 1996. The mean age of the MAP-related fatalities during this period was 30.7 years and occurred predominantly in males (73%). The manner of deaths included natural, accidental, suicidal, homicidal and uncertain causes of deaths, represented, respectively, by 31 (13%), 143 (59%), 28 (11%), 34 (14%) and 8 (3%) cases. As a consequence of the endemic problem and public hazard created by illicit drug abuse in Taiwan, stronger anti-drug programs and curbs to illicit drug addiction were required urgently from the government and from the public. The findings of this study represent the results of utilization of an anti-drug program in Taiwan (Support by NSC 85-2331-B-016-092). PMID- 9987868 TI - Insect succession on buried carrion in two biogeoclimatic zones of British Columbia. AB - We established a database of insect succession on buried carrion in two biogeoclimatic zones of British Columbia over a 16-month period beginning June 1995. Pig (Sus scrofa L.) carcasses were buried shortly after death in the Coastal Western Hemlock and Sub-boreal Spruce biogeoclimatic zones of British Columbia. Buried pigs exhibited a distinct pattern of succession from that which occurred on above-ground carrion. The species composition and time of colonization for particular species differed between the two zones. Therefore ideally, a database of insect succession on buried carrion should be established for each major biogeoclimatic zone. We did not observe maggot masses on any of the buried carcasses; therefore, the presence of maggot masses may indicate a delayed burial. Soil temperature was a better indicator of internal buried carcass temperature (r2 = 0.92, p < 0.0001) than was ambient air temperature (r2 = 0.60, p < 0.0001); thus soil temperature should be used to determine developmental rates of insects for determination of the postmortem interval by a forensic entomologist. PMID- 9987870 TI - A visual method of determining the sex of skeletal remains using the distal humerus. AB - This study introduces a new method of determining sex based on four morphological features of the posterior, distal humerus. The technique was developed on a 20th century anatomy series, the University of Toronto Grant Skeletal Collection, and was tested on 35 known individuals from the University of New Mexico Documented Collection and 93 individuals from the William M. Bass Donated Skeletal Collection. Four statistically significant characteristics relating to the carrying angle of the arm are identified (p < 0.05). Together, they are capable of determining sex with 92% accuracy. PMID- 9987871 TI - Midline facial tissue thicknesses of subadults from a longitudinal radiographic study. AB - Fourteen midline facial tissue measurements were taken from 615 tracings of lateral radiographs of subadults aged 8 to 20 years. The data were collected to examine two questions: First, are there differences in facial soft tissue measurements between female and male subadults? Second, do facial tissue thicknesses change as children grow? Results indicate that males exhibit greater tissue thickness measurements than females but only significantly so after age 14. Results further indicate a trend of increased facial tissue thickness as individuals grow; however, correlations are weak and suggest that other unknown factors are involved. Data presented here can be of practical application for facial reproduction in forensic cases. PMID- 9987869 TI - Mechanisms of aortic injury in fatalities occurring in motor vehicle collisions. AB - Case reviews based on autopsy studies have shown that motor vehicle collisions cause between 50 and 90% of traumatic aortic ruptures. Very few studies have analyzed the nature and severity of the collision forces associated with this injury. Our passenger car study (1984-1991) examined 36 collisions in which 39 fatally injured victims sustained aortic trauma. In this injury group, a disproportionate number of heavy truck and roadside fixed-object impacts occurred. Vehicle crash forces were generally severe and were either perpendicular or oblique to the vehicle surface. Intrusion into the occupant compartment was a significant factor in most of these fatal injuries. Occupant contact with vehicle interior surfaces was identified in most cases, and occupant restraints were often ineffective, especially in side collisions. The more elderly victims were seen in the least severe collisions. The most frequent site of aortic rupture was at the isthmus. A majority of victims had rib/sternal fractures indicating significant chest compression. Of the various traumatic aortic injury mechanisms proposed in motor vehicle impacts, the favored theories in the literature combine features of rapid deceleration and chest compression. This study supports that predominant impression, concluding that rapid chest deceleration/compression induces torsional and shearing forces that result in transverse laceration and rupture of the aorta, most commonly in the inherently vulnerable isthmus region. PMID- 9987872 TI - The analysis of methamphetamine hydrochloride by thermal desorption ion mobility spectrometry and SIMPLISMA. AB - Ion mobility spectrometry (IMS) has been successfully developed to yield an advanced portable instrument. Such instruments may detect trace quantities of regulated substances at the crime scene. The atmospheric ion chemistry that occurs within the instrument may hinder the determination of analytes in real world samples. The use of temperature programming adds an extra dimension to the data that improves the selectivity of the IMS data when chemometric processing is applied. The SIMPLISMA (SIMPLe-to-use-Interactive Self-Modeling Mixture Analysis) method is demonstrated for modeling variances in IMS data that are introduced from the temperature program. Methamphetamine hydrochloride IMS peaks are obscured by chemical interferences that arise from cigarette smoke residue. Cigarette smoke residue is pervasive at crime scenes. The ability of SIMPLISMA to resolve the analyte peaks that correspond to methamphetamine hydrochloride from interfering cigarette smoke has been demonstrated. A reduced mobility of 1.62 cm2V-1s-1 was observed for a methamphetamine hydrochloride monomer. With the IMS drift tube at room temperature, a second peak was observed at 1.24 cm2V-1s-1, which is consistent with a dimer ion. This peak has not been previously reported. PMID- 9987873 TI - Forensic evidence based on mtDNA from dog and wolf hairs. AB - In six forensic cases involving murder, bank robbery, theft and poaching, evidence material comprising shed hairs supposedly originating from dogs or wolves was analyzed by mitochondrial (mt) DNA sequencing. A 79 bp segment of the control region was amplified, sequenced, and compared with an established database of the domestic dog and wolf populations. In three murder cases exclusions of all eight suspects could be made. Furthermore, two of the murders could be linked to each other by a rare sequence variant, and the breed of the dog was indicated. In a theft case and a bank robbery a link could be established between the evidence material and the suspects. In a case of suspected wolf poaching, it could be established that the evidential material was of dog rather than wolf origin. We conclude that single hairs from common pets are suitable for DNA analysis and that the described method has proved to be a valuable tool for forensic investigations. PMID- 9987874 TI - Lewis (FUT3) genotypes in two different Chinese populations. AB - The allelic frequencies of the alpha (1,3/4)fucosyltransferase gene (FUT3) in two different Chinese populations (138 individuals in Shenyang and 154 in Guangzhou) were investigated using PCR-RFLP and nucleotide sequencing methods. The common alleles in the Oriental population, Le (wild type allele), le59,508 (with the mutations at nucleotide (nt) 59T-->G and nt 508G-->A) and le59,1067 (with the mutations at nt 59T-->G and nt 1067T-->A) were encountered, and also the rare alleles, le1067 (with the mutation at nt 1067T-->A) and Le59 (with the mutation at 59T-->G), were observed in these Chinese populations. In addition, the common allele in Caucasians, le202,314 (with the mutations at nt 202T-->C and nt 314C- >T), was found in the Oriental population for the first time. The allelic frequencies of the Le, Le59, le59,508, le59,1067, le202,314, and le1067, were 0.750, 0.011, 0.145, 0.054, 0.036, and 0.004 in the Shenyang population and 0.675, 0.026, 0.14, 0.123, 0.026, and 0.010 in the Guangzhou population, respectively. The presence of the alleles containing either the 59 mutation (Le59) or the 1067 mutation (le1067) suggested that the allele le59,1067 may have originated by recombination between them. PMID- 9987875 TI - Analysis and interpretation of short tandem repeat microvariants and three-banded allele patterns using multiple allele detection systems. AB - The Palm Beach County Sheriffs Office (PBSO) Crime Laboratory and the Alabama Department of Forensic Sciences (ADFS) have validated and implemented analysis of short tandem repeat (STR) sequences on casework using silver staining kit and SYBR Green I detection systems and are presently validating fluorescently tagged STR alleles using the Hitachi FMBIO 100 instrument. Concurrently, the Broward County Sheriff's Office (BSO) Crime Laboratory is validating the ABI Prism310 Genetic Analyzer capillary electrophoresis STR detection system (ABI CE310) from Perkin Elmer Applied BioSystems. During the course of analyzing over 10,000 individuals for the STR loci CSF1PO, TPOX and THO1 (CTT) using silver staining for allele detection, 42 samples demonstrated alleles that were "off ladder," contained three-banded patterns at a single locus, or exhibited an apparent THO1 "9.3,10" allele pattern. PBSO, ADFS and BSO Crime Laboratories have collaborated on the verification of the allele patterns observed in these 42 samples using the following allele detection systems: (1) manual silver staining, (2) SYBR Green I staining, and/or (3) fluorescently tagged amplified products separated by polyacrylamide gel electrophoresis or capillary electrophoresis followed by laser detection. Regardless of the CTT allele detection system utilized, concordant results were obtained for 41 of the 42 samples. The only exception was a sample in which a wide band within the THO1 locus was identified as a THO1 "9.3, 10" genotype by silver staining kit and SYBR Green I staining but was verified to be a THO1 "9.3" homozygote by all other allele detection systems. Manual allele detection could readily identify microvariants, as a visual assessment of stained gels clearly shows that alleles do not migrate coincident with well-characterized allele size standards. As would be predicted, however, the manual detection systems did not provide adequate resolution to approximate the basepair size for off-ladder variants. All fluorescent software program systems were consistent in designating alleles "not in range" or "off ladder," thereby indicating true microvariants. All single-locus three-banded patterns were detected using all of the STR multiplex systems. In addition, individual locus-specific primers verified multiplexed amplified products were specific for the locus in question. PMID- 9987876 TI - DNA-PCR analysis of bloodstains sampled by the polyvinyl-alcohol method. AB - Among the usual techniques of sampling gunshot residues (GSR), the polyvinyl alcohol method (PVAL) includes the advantage of embedding all particles, foreign bodies and stains on the surface of the shooter's hand in exact and reproducible topographic localization. The aim of the present study on ten persons killed by firearms was to check the possibility of DNA-PCR typing of blood traces embedded in the PVAL gloves in a second step following GSR analysis. The results of these examinations verify that the PVAL technique does not include factors that inhibit successful PCR typing. Thus the PVAL method can be recommended as a combination technique to secure and preserve inorganic and biological traces at the same time. PMID- 9987877 TI - Blood grouping of mixed bloodstains using immunocytochemical methods. AB - Immunocytochemical methods to determine the ABO blood group of each blood of mixed bloodstains have been developed. Mixed bloodstains were made on surgical blades and a cedar board. The blades were dipped into blood and then dipped into blood of a different group at intervals of 30, 20, 15, 10 and 5 s. Two drops of blood were dropped on a cedar board and then two drops of blood of a different group were dropped there at the same intervals. The bloodstains were dried for a week. The blood samples were removed from the blades or the cedar board and processed according with a routine histological method. Three serial thin sections were obtained. After deparaffinization, the sections were treated in papain solution for 2 h at 36 degrees C, to unmask antigenic sites on red cell membranes. The labeled streptavidin-biotin (LSAB) and peroxidase-anti-peroxidase (PAP) methods were used to detect A and B antigens, and an indirect immunocytochemical method for H antigen. These immunocytochemical methods showed specific immunologic reactions and allowed determination of the blood group of each blood of mixed bloodstains. Further, these methods indicated a possibility to determine who was stabbed first, in cases where two or more victims were stabbed with a single knife. PMID- 9987878 TI - Applications of focused ion beam systems in gunshot residue investigation. AB - Scanning ion microscopy technology has opened a new door to forensic scientists, allowing the GSR investigator to see inside a particle's core. Using a focused ion beam, particles can be cross-sectioned, revealing interior morphology and character that can be utilized for identification of the ammunition manufacturer. PMID- 9987879 TI - Metal contamination in illicit samples of heroin. AB - We analyzed 198 illicit heroin samples from Andalusia (southern Spain) to determine the contents of various metals (cadmium, calcium, copper, iron, manganese and zinc) with a view to investigating a new aspect of the drug purity and the conditions under which the drugs are used by addicts. Calcium was found in 93.4% of the samples and always at high concentrations, which can be ascribed to adulteration of the heroin by addicts with thinners and excipients containing salts of this metal such as calcium bicarbonate. Also, all samples were found to contain variable amounts of zinc and substantial amounts of iron, probably because it is the most common metal found in metal containers used in the extraction of morphine from the opium poppy. Only cadmium and, to a lesser extent, zinc, copper, and iron, are among the metals detected in heroin that can increase the inherent toxicity of the drug while always taking into account the maximum values. PMID- 9987880 TI - Problems in mass-disaster dental identification: a retrospective review. AB - A wide variety of problems may prevent or hinder a dental-identification (ID) team in its efforts to identify mass casualties. Since these problems have been infrequently reported in a comprehensive manner, the authors identified and summarized these problems to increase the awareness of dental-ID team members and to prepare them for future mass-disaster missions. The authors analyzed 50 mass disasters--ten in which the authors as members of military dental ID teams played a major role and 40 from the literature--and summarized problems that they confronted. PMID- 9987881 TI - Validation of highly polymorphic fluorescent multiplex short tandem repeat systems using two generations of DNA sequencers. AB - Validation studies are a crucial requirement before implementation of new genetic typing systems for clinical diagnostics or forensic identity. Two different fluorescence-based multiplex DNA profiling systems composed of amelogenin, HumD21S11 and HumFGA (referred to as multiplex 1A), and HumD3S1358, HumD21S11 and HumFGA (multiplex 1B) have been evaluated for use in forensic identification using the Applied Biosystems Model 373A and Prism 377 DNA Sequencers, respectively. Experiments were aimed at defining the limit of target DNA required for reliable profiling, the level of degradation that would still permit amplification of the short tandem repeat (STR) loci examined, and the robustness of each locus in the multiplexes after samples were exposed to environmental insults. In addition, the specificity of the multiplexes was demonstrated using nonhuman DNAs. Forensically relevant samples such as cigarette butts, chewing gum, fingernails and envelope flaps were processed using both an organic extraction procedure and a QIAamp protocol. DNAs and resultant multiplex STR profiles were compared. The validation of the triplex STR systems was extended to include over 140 nonprobative casework specimens and was followed with a close monitoring of initial casework (over 300 exhibits). Our results document the robustness of these multiplex STR profiling systems which, when combined with other multiplex systems, could provide a power of discrimination of approximately 0.9999. PMID- 9987882 TI - Allele distribution at nine STR loci--D3S1358, vWA, FGA, TH01, TPOX, CSF1PO, D5S818, D13S317 and D7S820--in the Japanese population by multiplex PCR and capillary electrophoresis. AB - Nine tetranucleotide short tandem repeat (STR) loci, D3S1358, vWA, FGA TH01, TPOX, CSF1PO, D5S818, D13S317 and D7S820, were analyzed in the Japanese population with a newly released kit for personal identification using multiplex PCR with fluorescent-labeled primers following capillary electrophoresis. The observed heterozygosities were 0.67, 0.77, 0.82, 0.61, 0.62, 0.73, 0.78, 0.81 and 0.74, respectively, and the combined discrimination power of the nineplex was 0.9999999991. None of the nine loci deviated from Hardy-Weinberg equilibrium expectations using the chi-square test, homozygosity test, likelihood ratio test and exact test after the grouping of the alleles. The nine STR loci allele frequencies were significantly different from those of other ethnic populations. PMID- 9987883 TI - LDLR, GYPA, HBGG, D7S8 and GC allele and genotype frequencies in the northwest Italian population. AB - Allele and genotype frequencies for five PCR-based DNA markers (LDLR, GYPA, HBGG, D7S8 and GC) were determined in 100 unrelated individuals from Piedmont (Northwest Italy). All five Ioci met Hardy-Weinberg expectations in the sampled population. The combined PD and CE were, respectively, 0.995 and 0.697. Frequencies obtained were compared with other previously published data on Caucasian populations with no significant differences. The genetic data from this study, in addition to those already collected by other groups, contribute to the expansion of the Italian DNA database suitable for forensic casework and paternity testing. PMID- 9987884 TI - Deoxyribonuclease I phenotyping from saliva stains. AB - Good typing results were obtained using a newly developed method for extraction and purification of deoxyribonuclease I (DNase I) from saliva stains. Previously, DNase I phenotyping from saliva stains has been unsuccessful because of low enzyme activity and heavy contamination. Salivary DNase I was extracted from stains using phosphate buffer containing Nonidet P-40. Extracts were purified using Phenyl Sepharose CL-4B gel. Electrophoresis was performed, and DNase I was successfully phenotyped. All of the DNase I phenotypes, which were obtained from saliva stains using this new method, were identical to the phenotypes determined from urine samples. Moreover, DNase I was correctly phenotyped from saliva stains that had been stored for over three months at room temperature or at 37 degrees C. These results suggest that DNase I polymorphisms provide valuable information for forensic characterization of saliva stains. PMID- 9987885 TI - DNA typing as a strategy for resolving issues relevant to forensic toxicology. AB - To investigate aircraft accidents, multiple postmortem biological samples of victims are submitted to the Civil Aeromedical Institute for toxicological evaluation. However, depending upon the nature of a particular accident, their body components are often scattered, disintegrated, commingled, contaminated, and/or putrefied. These factors impose difficulties with victim identification, tissue matching, and consequently authentic sample analysis and result interpretation. Nevertheless, these limitations can be overpowered by DNA typing. In this regard, three situations are hereby exemplified where DNA analysis was instrumental in resolving a tissue mismatching/commingling issue, pinpointing an accessioning/analytical error, and interpreting an unusual analytical result. Biological samples from these cases were examined for six independently inherited genetic loci using polymerase chain reaction (PCR) suitable for analyzing degraded DNA generally encountered in putrefied/contaminated samples. In the first situation, three of five specimen bags from one accident were labeled with two different names. DNA analysis revealed that one of these bags actually had commingled specimens, originating from two different individuals. Therefore, the sample was excluded from the final toxicological evaluation. In the second situation, an unacceptable blind control result was reported in a cyanide batch analysis. By comparing DNA profiles of the batch samples with those of the known positive and negative blind controls, it was concluded that the error had occurred during the analysis instead of accessioning. Accordingly, preventive measures were taken at the analytical level. The third situation was related to the presence of atropine at toxic concentrations in the blood (318 ng/mL) and lung (727 ng/g) with its absence in the liver, spleen, and brain. DNA analysis of the blood and liver samples exhibited their common identity, ensuring that the submitted samples had indeed originated from one individual. The selective presence of atropine was attributed to its possible administration into the thoracic cavity by the emergency medical personnel at the accident site for resuscitation, but circulatory failure prevented its further distribution. These examples clearly demonstrate the applicability of the PCR-based DNA typing to enhance the effectiveness of forensic toxicology operation. PMID- 9987886 TI - A study involving venlafaxine overdoses: comparison of fatal and therapeutic concentrations in postmortem specimens. AB - The distribution and redistribution of venlafaxine were investigated in two overdoses and several cases involving the therapeutic use of venlafaxine. Blood, liver, bile vitreous humor, urine and gastric contents were analyzed using high performance liquid chromatography with ultraviolet detection. Blood concentrations of venlafaxine in the two overdose cases were 53 mg/L and 78 mg/L. Comparison of venlafaxine concentrations in blood samples taken at different times after death revealed increases in concentrations over time, suggesting the possible postmortem redistribution of venlafaxine. PMID- 9987887 TI - Cyclohexyl nitrite encounter. AB - A brown glass bottle containing yellow liquid was submitted for examination for the presence of common controlled substances. While no controlled substances were detected, the liquid was identified as impure cyclohexyl nitrite, a compound of the same chemical class as amyl and butyl nitrite, which are known for their abuse potential. A bottle labeled cyclohexyl nitrite, but not confirmed by analysis, is the only known previous case submitted to this lab. The case history, examination, and analytical results are presented. PMID- 9987888 TI - Comparing the alleged weapon with damage to clothing--the value of multiple layers and fabrics. AB - The examination of damage to multiple layers of clothing of an attempted murder victim is described. The large number of cuts to the garments, the multiple layers and the varying types of fabric composing these garments gave valuable information as to the possible implement causing the damage. The results also show that some types of material may better reflect the geometry of the suspect weapon than others. PMID- 9987889 TI - Determination of the size of a foreign body in the eye using image analysis of its roentgenogram. AB - The case of a computer-enhanced image analysis of X-ray pictures of a pellet in the orbit of a man who sustained a shotgun injury to his right eyeball is presented. The man was shot accidentally during a pheasant hunt. Two hunters were shooting simultaneously but they were using three different sizes of pellet--3.0, 3.5 and 4.0 mm. One of the pellets hit a third man in the eye. He sustained serious injury with a resultant loss of sight in this eye despite immediate medical treatment. Unfortunately the pellet could not be removed from the orbit, but it was necessary to establish who was responsible for the injury. The problem lay in determining the specification and size of the pellet at that moment. The problem was solved using computer-enhanced video image analysis of the X-ray pictures of the pellets. The image processor LUCIA G (http(/)/www.lim.cz) was used. PMID- 9987890 TI - A fatality due to the intranasal abuse of methylphenidate (Ritalin). AB - A fatality in a teenager from the recreational intranasal abuse of methylphenidate (Ritalin) is reported. The prescribed use of methylphenidate (Ritalin) in the treatment of attention deficit and/or hyperactivity disorder is widespread. The intranasal abuse of methylphenidate (Ritalin) among teenagers is becoming increasingly more recognized. Previous deaths from the parenteral abuse of methylphenidate (Ritalin) have been reported. This fatality is the first reported from its intranasal abuse. PMID- 9987891 TI - Stereochemical determination of selegiline metabolites in postmortem biological specimens. AB - In this study, findings related to an aircraft accident are reported. Biological specimens collected at autopsy from the pilot of the fatal accident and two types of tablets found at the accident scene were submitted for toxicological evaluation. It was determined that the pilot was dead at the crash site and the cause of death was multiple traumatic injuries. The tablets were identified as selegiline and levodopa, commonly prescribed for the treatment of Parkinson's disease. Selegiline, a stereospecific compound, is biotransformed into (-)-N desmethylselegiline, (-)-methamphetamine, and (-)-amphetamine. The latter two levorotatory metabolites cannot be easily distinguished by routine analysis from their dextrorotatory isomers, which are controlled substances. It was, therefore, prudent to differentiate these isomers to determine if they resulted from the ingestion of a controlled substance, (+)-methamphetamine. Initial immunoassay drug screenings revealed the presence of amphetamine class drugs (867 ng/mL) in urine, amphetamine/methamphetamine (261 ng/mL) in urine, and methamphetamine (46 ng/mL) in blood. The gas chromatography-mass spectrometry (GC/MS) results revealed the presence of methamphetamine in the concentrations of 76 ng/mL of blood and 685 ng/mL of urine. The concentration of amphetamine was 52 ng/mL in blood and 320 ng/mL in urine. To determine the stereospecificity of these amines, the isolated amines from the biosamples were derivatized by a stereospecific agent, (S)-(-)-N-(trifluoroacetyl)-prolyl chloride, and characterized by a GC/MS method to be levorotatory. The 2.14 ratio of (-)-methamphetamine to (-) amphetamine concentrations in the urine was consistent with a selegiline study in the recent literature. The stereospecific analysis, in conjunction with the history of the pilot being on Parkinson's medications, suggests that the source of these amines was selegiline. This conclusion substantiates the importance of the identification of enantiomers in evaluating and interpreting related analytical results for accident investigations. PMID- 9987892 TI - Recommendations for toxicological investigations of drug-facilitated sexual assaults. AB - The recent increase in reports of drug-facilitated sexual assaults has caused alarm in the general public and prompted forensic toxicologists from across North America to address the toxicological issues surrounding this matter. The authors have developed recommendations and guidelines to inform law enforcement, medical, and scientific personnel of the requirements for performing successful toxicological examinations in cases of drug-facilitated rape. PMID- 9987893 TI - In vitro stability of endogenous gamma-hydroxybutyrate in postmortem blood. PMID- 9987894 TI - Proceedings of the International Workshop on Canine Genetics. Ithaca, New York, USA. July 12-13, 1997. PMID- 9987895 TI - DogMap: an international collaboration toward a low-resolution canine genetic marker map. DogMap Consortium. PMID- 9987897 TI - Development of comparative anchor tagged sequences (CATS) for canine genome mapping. AB - The development of a useful genetic map of the domestic dog would benefit by the inclusion of type I markers; coding genes that can connect the canine map to the homologous gene maps of other mammalian species. A group of 280 comparative anchor tagged sequences (CATS), and universal mammalian sequence tagged sites (UM STS), were optimized for canine assessment. One hundred and five were screened for genetic polymorphism among nine canine breeds and three wild species of Canis in an attempt to promote gene mapping of comparative type I markers. Three categories of variation--size, restriction fragment length polymorphism (RFLP), and single-strand conformation polymorphism (SSCP)--were assessed. The data showed that 50% of the type I markers discriminate between species and 40% showed genetic variation among dog breeds. Although polymorphism incidence between nominated breeds for gene mapping is more limited than found for established reference pedigrees in other species, the concept and application of these CATS and UM-STS markers is useful in capturing the comparative information required for the full application and efficacy of the dog gene map. PMID- 9987896 TI - Toward a framework linkage map of the canine genome. AB - Selective breeding to maintain specific physical and behavioral traits has made the modern dog one of the most physically diverse species on earth. One unfortunate consequence of the common breeding practices used to develop lines of dogs with the desired traits is amplification and propagation of genetic diseases within distinct breeds. To map disease loci we have constructed a first generation framework map of the canine genome. We developed large numbers of highly polymorphic markers, constructed a panel of canine-rodent hybrid cell lines, and assigned those markers to chromosome groups using the hybrid cell lines. Finally, we determined the order and spacing of markers on individual canine chromosomes by linkage analysis using a reference panel of 17 outbred pedigrees. This article describes approaches and strategies to accomplish these goals. PMID- 9987898 TI - FISH mapping and identification of canine chromosomes. AB - The karyotype of the domestic dog (Canis familiaris) is widely accepted as one of the most difficult mammalian karyotypes to work with. The dog has a total of 78 chromosomes; all 76 autosomes are acrocentric in morphology and show only a gradual decrease in length. Standardization of the canine karyotype has been performed in two stages. The first stage dealt only with chromosomes 1-21 which can be readily identified by conventional G-banding techniques. The remaining 17 autosomal pairs have proven to be very difficult to reliably identify by banding alone. To facilitate the identification of all canine chromosomes, chromosome specific paint probes have been produced by DOP-PCR from flow-sorted dog chromosomes. Each paint probe has been used for FISH to identify the corresponding chromosome(s), allowing precise identification of all 78 canine chromosomes. The identification of the undesignated 17 autosomal pairs has been agreed upon by the standardization committee during the second stage of their role. Cosmid clones containing microsatellite markers may now be conclusively assigned to their chromosomal origin by simultaneous dual-color FISH with the corresponding paint probe. In this way a collection of chromosome-specific cosmid clones is being constructed, comprising at least one marker per chromosome, which will allow anchoring of existing and future linkage groups to the physical map. PMID- 9987899 TI - Working with canine chromosomes: current recommendations for karyotype description. AB - There is an increasing interest in genomic research on the domestic dog (Canis familiaris). However, these investigations are complicated by the canine karyotype comprising 76 acrocentric autosomes of similar size and shape and the metacentric sex chromosomes. None of the numerous published ideograms and karyotypes has yet been generally accepted. The present article gives a review of these descriptions of the canine karyotype. The two most recent nomenclatures and the current efforts toward a standardized canine karyotype made by the Committee for the Standardized Karyotype of the Dog are discussed in detail and recommendations for future use of a nomenclature for the canine karyotype are given. PMID- 9987900 TI - Organization of the canine major histocompatibility complex: current perspectives. AB - The dog is a valuable model for studying several human diseases as well as one of the most important models for organ transplantation. Important to understanding the pathophysiology or development of some of these diseases is an understanding of the canine major histocompatibility complex (MHC) or dog leukocyte antigen (DLA). Initial characterization of the DLA involved primarily cellular, serological, and biochemical analyses. Later a molecular analysis of the DLA region was begun. There are at least four complete class I genes: DLA-88, DLA-12, DLA-64, and DLA-79. DLA-88 is highly polymorphic, with more than 40 alleles obtained from an examination of 50 mixed breed dogs. The other class I loci are less polymorphic, with fewer than 12 alleles each. In the class II region there is one complete DRB gene called DLA-DRB1 with at least 24 alleles and one full length DQB gene, DLA-DQB1, with 20 alleles characterized to date. DLA-DQA is less polymorphic with nine alleles and DLA-DRA appears monomorphic. Two highly polymorphic canine microsatellite markers, one located in the class I region and one located in the class II region, can be used to identify DLA-matched and mismatched dogs within families for organ transplantation experiments. Future projects include mapping the DLA region by pulsed-field gel electrophoresis and using a recently constructed canine bacterial artificial chromosome (BAC) library to search for new genes within the DLA. The dog has been a useful model for understanding several human diseases such as gluten-sensitive enteropathy (Hall and Batt 1990), rheumatoid arthritis (Halliwell et al. 1972), narcolepsy (Tafti et al. 1996), and systemic lupus erythematosus (Lewis and Schwartz 1971, Teichner et al. 1990), as well as an important model for solid organ and hematopoietic stem cell transplantation (Storb and Deeg 1985). Much of the impetus behind efforts to characterize the canine MHC comes from its importance in transplantation. In spite of the dog's importance in studying human disease and in immunology, molecular analysis of the DLA has lagged behind that of the mouse and human as well as several agricultural animals. PMID- 9987901 TI - A comparative approach to physical and linkage mapping of genes on canine chromosomes using gene-associated simple sequence repeat polymorphisms illustrated by studies of dog chromosome 9. AB - We describe and illustrate a comparative approach to creating physical and linkage maps of genes on dog chromosomes. The approach is particularly useful in species, like the dog, which have a rudimentary gene map not integrated with microsatellite loci. Human or mouse cDNAs for genes to be mapped are used to isolate cosmid or phage clones from dog genomic libraries. Clones verified to contain the homologous canine gene coding sequences are screened for "gene associated" simple sequence repeat polymorphisms (SSRPs). The unique sequences flanking the repeats are used to design PCR primers to amplify the repeat and gene-associated SSR length differences that are informative for linkage analysis used in canine pedigrees to study linkage between loci or with diseases. The same canine clones are employed as probes in fluorescence in situ hybridization (FISH) studies to physically map the loci to specific sites on dog chromosomes. This approach creates a combined gene and gene-associated microsatellite anchor locus framework map. In this article we review our recent use of this approach to map a series of genes found on human chromosome 17 (HSA17) to two dog chromosomes. Canine chromosome 9 (CFA9) contains 11 loci found on HSA17q, while two genes from HSA17p map to CFA5, demonstrating disruption of HSA17 synteny at the centromere. The order of 11 HSA17q genes on CFA9 was conserved in the dog, but the entire group is inverted with respect to the centromere when compared to human and mouse. Maps created by this approach can be used to advantage for integrating anonymous microsatellites with gene maps, including microsatellites found in genome scans to be linked to canine diseases. This makes it possible to identify the homologous chromosomal region in the human or mouse genome and to make use of this information in formulating hypotheses regarding candidate genes, as has recently been illustrated by other investigators. PMID- 9987902 TI - Teaching a new dog old tricks: identifying quantitative trait loci using lessons from plants. AB - Locating quantitative trait loci (QTL) in mammalian systems has proven difficult due to the lack of genetic control and reproducibility, as well as the expense of maintaining sufficiently large populations for genotyping and phenotyping. In plants, populations of recombinant inbred lines (progeny bred to homozygosity from a single cross) do not have these problems. Methods developed to identify QTL in a recombinant inbred soybean population provide a basis for analysis of a suitable mammalian population, such as Portuguese water dogs in the United States. The more than 6,000 dogs have accurate pedigrees, available phenotypic data and samples for genotyping, as well as interesting quantitative trait variation. The computer program Georgie allows us to choose large subpopulations with desirable characteristics such as high degrees of consanguinity that capture some of the benefits of recombinant inbred lines in plants. Computer simulations extending methods developed for simpler plant populations indicate that QTL with realistic effects can be identified from such subpopulations. Currently we are developing markers and collecting phenotypic and genotypic data from this population to begin the process of unraveling the genetic basis of quantitative traits in dogs. PMID- 9987904 TI - Use of canine microsatellite polymorphisms in forensic examinations. AB - A forensic case report is presented. Using pooled SSCP analysis of three polymorphic microsatellites one possible candidate was excluded in a time and cost saving way. PMID- 9987903 TI - Use of cosmid-derived and chromosome-specific canine microsatellites. AB - The majority of microsatellite markers being used to generate the emerging genetic linkage maps of the dog are derived from small-insert, random clones. While such markers are easy to generate, they have the disadvantage that they cannot easily be physically mapped by fluorescence in situ hybridization (FISH), making it difficult to assess the extent of genome coverage represented by such maps. In contrast, microsatellite markers from large-insert libraries enable the linkage groups within which they fall to be physically anchored to specific chromosomes. One aim of our work is to identify at least one microsatellite containing cosmid clone for each canine chromosome, to ensure that linkage groups exist for all chromosomes. This is particularly important for a species with as complex a karyotype as the dog. Locating two cosmids on each chromosome would allow the orientation of the linkage groups to be established. Chromosomal locations of cosmid clones containing microsatellites have been determined by FISH and confirmed using canine chromosome-specific paints. Microsatellite sequences have been genotyped on the DogMap reference family. Microsatellites derived from flow-sorted, chromosome-specific libraries represent another source of useful markers. Initial studies have been carried out on the canine X chromosome, on which markers were underrepresented in our initial studies. PMID- 9987905 TI - Photoreceptor dysplasia (pd) in miniature schnauzer dogs: evaluation of candidate genes by molecular genetic analysis. AB - Photoreceptor dysplasia (pd) is one of a group of at least six distinct autosomal and one X-linked retinal disorders identified in dogs which are collectively known as progressive retinal atrophy (PRA). It is an early onset retinal disease identified in miniature schnauzer dogs, and pedigree analysis and breeding studies have established autosomal recessive inheritance of the disease. Using a gene-based approach, a number of retina-expressed genes, including some members of the phototransduction pathway, have been causally implicated in retinal diseases of humans and other animals. Here we examined seven such potential candidate genes (opsin, RDS/peripherin, ROM1, rod cGMP-gated cation channel alpha subunit, and three subunits of transducin) for their causal association with the pd locus by testing segregation of intragenic markers with the disease locus, or, in the absence of informative polymorphisms, sequencing of the coding regions of the genes. Based on these results, we have conclusively excluded four photoreceptor-specific genes as candidates for pd by linkage analysis. For three other photoreceptor-specific genes, we did not find any mutation in the coding sequences of the genes and have excluded them provisionally. Formal exclusion would require investigation of the levels of expression of the candidate genes in pd-affected dogs relative to age-matched controls. At present we are building suitable informative pedigrees for the disease locus with a sufficient number of meiosis to be useful for genomewide screening. This should identify markers linked to the disease locus and eventually permit progress toward the identification of the photoreceptor dysplasia gene and the disease-causing mutation. PMID- 9987906 TI - Toward a dog radiation hybrid map. AB - Dog fibroblasts grown from a biopsy performed in a male mongrel were fused after gamma irradiation with thymidine kinase-deficient hamster cells and cultivated in selection medium. A total of 148 clones were obtained and screened by means of PCR amplification using primers corresponding to a dog-specific short repetitive element and to dog microsatellites and genes. One hundred seven cell lines were selected and grown in roller bottles and the distribution of 39 markers was analyzed in the extracted DNA. The results clearly indicate that this panel of hybrid cell lines should prove invaluable for constructing a map of the canine genome. In parallel, for more than 500 microsatellites present in the databases or screened from two libraries of short inserts, we have determined PCR conditions favoring dog-specific products even in the presence of hamster DNA. These highly polymorphic microsatellites should be useful in further linkage studies. We have also characterized 254 markers: dog genes, human expressed sequenced tags (huESTs), and traced orthologous amplified sequenced tags (TOASTs). Once mapped, these will constitute powerful tools to detect regions of conserved synteny in human and other mammalian genomes. PMID- 9987907 TI - Methods of analysis and resources available for genetic trait mapping. AB - Methods of genetic linkage analysis are reviewed and put in context with other mapping techniques. Sources of information are outlined (books, web sites, computer programs). Special consideration is given to statistical problems in canine genetic mapping (heterozygosity, inbreeding, marker maps). PMID- 9987908 TI - Phylogenetic relationships, evolution, and genetic diversity of the domestic dog. AB - The spectacular diversity in size, conformation, and pelage that characterizes the domestic dog reflects not only the intensity of artificial selection but ultimately the genetic variability of founding populations. Here we review past molecular genetic data that are relevant to understanding the origin and phylogenetic relationships of the dog. DNA-DNA hybridization data show that the dog family Canidae diverged about 50 million years ago from other carnivore families. In contrast, the extant canids are very closely related and diverged from a common ancestor about 10 million years ago. The evidence supporting a close relationship of dogs with gray wolves is overwhelming. However, dogs are remarkably diverse in mitochondrial and nuclear genes. Mitochondrial DNA analysis suggests a more ancient origin of dogs than has been indicated by the fossil record. In addition, dogs have originated from or interbred with wolves throughout their history at different times and different places. We test the possibility of an independent domestication event in North America by analysis of mtDNA variation in the Xoloitzcuintli. This unusual breed is believed to have been kept isolated for thousands of years and may be one of the most ancient breeds in North America. Our results do not support a New World domestication of dogs nor a close association of the Xoloitzcuintli with other hair-less breeds of dogs. Despite their phenotypic uniformity, the Xoloitzcuintli has a surprisingly high level of mtDNA sequence variation. Other breeds are also genetically diverse, suggesting that dog breeds were often founded with a large number of dogs from outbred populations. PMID- 9987909 TI - Random amplified polymorphic DNA (RAPD) sequences as markers for canine genetic studies. AB - Random amplified polymorphic DNA (RAPD) markers have been used in genetic studies of several plant and animal species. However, concerns exist about the reproducibility of RAPD-PCR reactions. Therefore, the use of specific 24mer primer pairs in standard PCR reactions has been suggested for reliable amplification of characterized polymorphic RAPD sequences. The purpose of this article is describe the application of the RAPD-PCR assay to genetic studies of dogs and to investigate the amplification of RAPD sequences with specific primer pairs. Of 240 decanucleotide primers tested by PCR, 34.6% resulted in amplification of at least one polymorphic fragment with samples of a Labrador retriever pedigree. We cloned and sequenced five of these RAPD fragments and synthesized specific 24mer primer pairs for each. Two primer pairs amplified a sequence exclusively from samples that were positive for the RAPD fragment, while three others amplified the respective sequence from all DNA samples. A new polymorphism was observed in the restriction digest products with Msel of one of the amplification products. None of the cloned sequences contains an open reading frame longer than 213 bases. Two sequences hybridized only to specific fragments of genomic DNA from samples that amplified the RAPD, the remaining three sequences hybridized to multiple sequences in all canine samples tested by Southern analysis. None of the five fragments hybridized to human or murine genomic DNA. Data suggested that RAPD sequences can be used as molecular markers in genetic studies of diseases in dogs. However, the use of specific primer pairs leads to loss of the RAPD polymorphism in three of five sequences tested. PMID- 9987910 TI - An outcrossed canine pedigree for linkage analysis of hip dysplasia. AB - Canine hip dysplasia (CHD) is a prevalent, debilitating, polygenic disease characterized by hip subluxation and laxity which results in osteoarthritis. We are developing an informative pedigree for linkage analysis of CHD. The seven greyhound founders had excellent hip conformation with high dorsolateral subluxation scores (percentage of femoral head covered by the dorsal acetabulum in a weight-bearing position) of 66 +/- 4% (mean +/- SD averaged over both hips) and low hip distraction (laxity) indices of 0.14 +/- 0.08. Nine greyhounds bred on site had radiographic evidence of ossification in the capital femoral chondroepiphysis at 7.7 +/- 0.9 days of age. At 8 months of age they had a mean distraction index of 0.24 +/- 0.08 and dorsolateral subluxation score of 76 +/- 1%. Of the four dysplastic Labrador retriever founders, three had mean age at onset of capital femoral chondroeplphyseal ossification of 20 +/- 7 days of age n = 3) and a mean distraction index of 0.46 +/- 0.1 accompanied by hip osteoarthritis. Thirty-four F1s had mean onset of capital femoral ossification (10.7 +/- 4.0 days of age) and mean dorsolateral subluxation scores (61 +/- 12%) similar to the greyhound founders, but distraction indices (0.42 +/- 0.2) more similar to the Labrador retriever founders. One F1 had CHD radiographically but none of 20 F1s had osteoarthritis at necropsy at 10 months of age. These data suggested that maximum passive laxity (as measured by the distraction index) and normal osseous conformation (as indicated by a high dorsolateral subluxation score) were both dominant traits and were controlled by separate quantitative trait loci (QTL). Forty-three back-crosses between F1s with the highest hip laxity and greyhound founders had mean onset of capital femoral ossification at 9.9 +/- 2.6 days of age. Of 10 dogs in the backcross generation that have reached 8 months of age, 2 had palpable subluxation without marked CHD radiographically. The mean distraction index of these dogs was 0.36 +/- 0.16 and the dorsolateral subluxation score was 65 +/- 5%. Although dogs in the backcross generation that were three-quarter greyhound had a broad range of hip laxity, a protective effect of the greyhound QTLs for good osseous conformation has mitigated thus far against subluxation and CHD. PMID- 9987911 TI - Inherited disorders in sexual development. PMID- 9987912 TI - Individual DNA bands obtained by RAPD analysis of canine genomic DNA often contain multiple DNA sequences. AB - The random amplified polymorphic DNA (RAPD) technique has been widely applied for genetic studies of plants, insects, and fungi, and recently has been used for studies in animals including dogs. To convert the RAPD marker into a classical PCR marker, the RAPD-PCR products are size-separated in an agarose gel and a specific DNA band is selected for potential association with a trait of interest. The DNA fragments present in the desired band are then cloned and sequenced using primers specific to the cloning vector, and the sequence is used to design a pair of classical PCR primers. Often a "positive clone" is identified based solely on a match of the size of the insert in the clone with the uncharacterized DNA band originally selected. We observed that single DNA bands obtained from RAPD-PCR using canine genomic DNA often contain DNA fragments of similar size but of different sequences. Based on this observation, we report here a modification of the protocol for RAPD analysis which will ensure that a promising RAPD marker selected based on initial screening is not lost for lack of a comprehensive investigation in the later experimental analysis. PMID- 9987913 TI - Analysis of randomly amplified polymorphic DNA (RAPD) for identifying genetic markers associated with canine hip dysplasia. AB - Canine hip dysplasia is a heritable developmental disease resulting, in part, from increased laxity in hip joints and is a precursor to degenerative joint disease. Identification of genetic markers linked to joint laxity would foster development of more accurate diagnostic methods, facilitate identification of the disease gene(s), and supplement efforts to establish physical/genetic maps of the canine genome. Work presented here describes analysis of randomly amplified polymorphic DNA in the search for markers which cosegregate with increased joint laxity in Canis familiaris, the domestic dog. The Boykin spaniel, a highly inbred breed afflicted with an extremely high incidence of hip dysplasia, served as a model for study of canine hip dysplasia. Only 5% of 200 random primers revealed significant polymorphisms within this breed. However polymorphisms were detected in seemingly nonpolymorphic amplification products when digested with restriction enzymes. Restriction digestion revealed polymorphisms in 15% of the monomorphic amplification products. Among the primers that revealed polymorphisms, one primer correctly identified 9 of 12 dogs with regard to joint laxity. However, extensive evaluation is required before any assertion can be made regarding linkage of this marker to joint laxity. Of interest, another primer amplified a genomic segment unique to the canine Y chromosome. PMID- 9987914 TI - Utility of canine microsatellites in revealing the relationships of pure bred dogs. AB - The variability of 19 canine microsatellite loci was examined within and between three pure breeds of dog. Their phylogenetic relationships were estimated by microsatellite and conventional genetic distances which indicated that greyhounds and German shepherds had longer diverse evolutionary histories, whereas Labrador retrievers were established much later. Our three breeds differ mainly in the relative frequencies of alleles at a locus and in distribution of alleles across loci. As a consequence of sampling strategy, greyhounds express significantly lower polymorphism than the other two breeds. However, some highly polymorphic microsatellite loci were common to all three breeds. High exclusion power of such loci made them valuable for parentage testing. Although the exclusion probability at a single locus is relatively low, it increases by every added microsatellite. The six most polymorphic ones sufficed to reach the exclusion probability of 99% in all three breeds tested here. As the majority of pedigree dogs have similar population structures, the data presented can be used to estimate the probability of biological paternity for any dog breed, despite the absence of appropriate population data. Polymorphic canine microsatellites proved to be valuable descriptors of population structure, and evolutionary and filial relationships. PMID- 9987915 TI - Microsatellite variation in the Australian dingo. AB - The dingo is thought to have arrived in Australia from Asia about 5,000 years ago. It is currently in danger because of interbreeding with domestic dogs. Several morphological, behavioral, and reproductive characteristics distinguish dingoes from domestic dog. Skull morphometrics are currently used to try to classify wild canids as pure dingo, dog, or hybrid. Molecular techniques based on diagnostic DNA differences between dogs and dingoes would make a much more reliable and practical test. A small number of markers (about 10) would allow detection of animals with domestic dog in their ancestry several generations back. We have typed 16 dingoes and 16 dogs of mixed breed for 14 microsatellites. The amount of variation in the Australian dingo is much less than in domestic dogs. The size distributions of microsatellites in the two groups usually overlap. The number of alleles in the dingo is much smaller in all cases. One dinucleotide repeat locus shows a size difference of 1 bp in allele classes between dog and dingo. This locus may be diagnostic for dog or dingo ancestry. The differences in distributions of alleles at other loci can also be used to classify animals using a likelihood method. PMID- 9987916 TI - A review of canine inherited bleeding disorders: biochemical and molecular strategies for disease characterization and carrier detection. AB - Many different inherited bleeding disorders have been identified in dogs, defined on the basis of quantitative, functional, or structural defects in specific hemostatic proteins or pathways. Most of these disorders are caused by single gene defects and biochemical assays provide an accurate measure of disease phenotype. Phenotypic disease classifications, however, are often genetically heterogeneous. Protein-based carrier detection assays are fast, inexpensive, and do not require specific identification of causative mutations. The limitations of these tests arise from variable "overlap" regions between carrier and clear dogs, influencing positive and negative predictive values of carrier detection tests within breed populations. Molecular diagnostic techniques enhance the accuracy of carrier detection, providing their clinical application takes into account the molecular heterogeneity underlying naturally occurring hemostatic defects in dogs. PMID- 9987917 TI - Biochemical basis of the beta-glucuronidase gene defect causing canine mucopolysaccharidosis VII. AB - Mucopolysaccharidosis type VII (MPS VII), or Sly syndrome, is an autosomal recessive lysosomal storage disorder resulting from the deficiency in the activity of the enzyme beta-glucuronidase (GUSB). To characterize the biochemical and molecular defect in GUSB-deficient MPS VII dogs, we have measured lysosomal enzyme activities, analyzed distribution of glycosaminoglycans (GAGs), and estimated the size and abundance of the GUSB gene product at the mRNA and protein level in normal, homozygous affected, and heterozygous carrier retinal pigment epithelium (RPE) samples. Compared to normal, only 2-5% and 40-60% of GUSB activity was detected in the affected and the carrier samples, respectively. The decrease in GUSB activity resulted in storage of GAGs predominantly heparan sulfate and chondroitin sulfate. A slight increase in storage of GAGs was also observed in the carrier sample. Northern blot analysis of affected and carrier RPE samples detected a 2.4 kb GUSB transcript similar in size and abundance to that of normal controls. In western blot analysis using anti-human GUSB antibody, three bands of size 78, 56, and 38 kDa were detected in normal samples, which were present at lower intensity in the carrier RPE samples and absent in the MPS VII-affected RPE samples. These results suggest that the mutant GUSB gene causes a posttranscriptional defect and produces an unstable protein. PMID- 9987918 TI - Cytogenetic, ras, and p53: studies in cases of canine neoplasms (hemangiopericytoma, mastocytoma, histiocytoma, chloroma). AB - Four case reports of mesenchymal neoplasms showing chromosomal abnormalities are presented. In a case of hemangiopericytoma trisomy 2 and centric fusion 19;21 were present. In a mastocytoma a deleted chromosome 35 was seen. A homogeneously staining region (HSR) on chromosome 1 was detected in a histiocytoma. Trisomy 5 and monosomy 31 were observed in a case of granulocytic sarcoma (chloroma). The lack of mutations in exons 1 and 2 of oncogenes N-ras, K-ras, and H-ras and exons 5, 6, 7, and 8 of tumor suppressor gene p53 in these four patients and in a larger series of investigated dogs (25 hemangiopericytomas, 12 mastocytomas, and 8 histiocytomas) is highlighted. PMID- 9987919 TI - Genetic studies in narcolepsy, a disorder affecting REM sleep. AB - Narcolepsy is a disabling sleep disorder characterized by excessive daytime sleepiness and abnormal manifestations of rapid eye movement (REM) sleep including cataplexy, sleep paralysis, and hypnagogic hallucinations. It is known to be a complex disorder, with both genetic predisposition and environmental factors playing a role. In humans, susceptibility to narcolepsy is tightly associated with a specific HLA allele, DQB1*0602. In humans and canines, most cases are sporadic. In Doberman pinschers and Labrador retrievers, however, the disease is transmitted as an autosomal recessive gene canarc-1 with full penetrance. This gene is not linked with the dog leukocyte antigen complex, but is tightly linked with a marker with high homology to the human mu-switch immunoglobulin gene. We have isolated several genomic clones encompassing the canarc-1 marker and the variable heavy chain immunoglobulin region in canines. These have been partially sequenced and have been mapped onto specific dog chromosomes by fluorescence in situ hybridization (FISH). Our results indicate that the mu-switch-like marker is not part of the canine immunoglobulin machinery. We are continuing to extend the genomic contig using a newly developed canine BAC library and attempting to identify the corresponding human region of conserved synteny. PMID- 9987920 TI - Strategies for identification of mutations causing hereditary retinal diseases in dogs: evaluation of opsin as a candidate gene. AB - Progressive retinal atrophy (PRA), like retinitis pigmentosa (RP) in man, represents a clinical classification grouping together a variety of hereditary diseases of the visual cells which have broadly similar clinical characteristics. At least six distinct autosomal recessive and one X-linked retinal disease locus have been identified. As one of the strategies to look for the gene defect causing the different forms of PRA, we are examining first the most promising candidate genes. These include those coding for photoreceptor-specific structural proteins and enzymes of the phototransduction pathway, especially those reported to cause RP. Preeminent among these candidates is the gene for rod opsin, in which multiple causative mutations have been identified in both dominant and recessive forms of RP. In addition, mutations in this gene are also causally associated with congenital stationary night blindness (CSNB) in man. We have used two strategies to examine the rod opsin gene for association with inherited retinal disease in dogs: (1) linkage to determine cosegregation of the disease locus with an intragenic polymorphic marker in the opsin gene in those breeds where suitable informative pedigrees were available; and (2) scanning the coding sequence of the gene in cases where only a limited number of affected or obligate heterozygous samples were available for a breed. We conclude that mutations in the rod opsin gene are not associated with PRA or CSNB in the 11 different dog breeds tested. PMID- 9987921 TI - Globoid cell leukodystrophy in cairn and West Highland white terriers. AB - Krabbe disease or globoid cell leukodystrophy (GLD) is an autosomal recessive disorder resulting from the defective lysosomal hydrolysis of specific galactolipids found primarily in myelin. This leads to severe neurological symptoms including seizures, hypotonia, blindness, and death, usually before 2 years of age in human patients. In addition to human patients, several animals, including dog, mouse, and monkey, have the same disease caused by a deficiency of galactocerebrosidase (GALC) activity. In this article we describe studies in cairn and West Highland white terriers (WHWT) affected with GLD. Through a screening test based on the molecular defect found in these breeds, over 50 cairn terrier carriers have been identified and a colony of five carrier dogs has been established. Affected dogs from this colony plus an affected WHWT were available for study. An affected WHWT was evaluated by magnetic resonance imaging at 6 and 11 months of age and pronounced changes in the T-2 weighted fast spin-echo images were found. Biochemical and pathological evaluation of the same dog after euthanasia at 12 months of age showed a large accumulation of psychosine in the brain and white matter filled with globoid cells. Some comparisons were made to younger affected and carrier dogs. Studies have shown successful transduction of cultured skin fibroblasts from an affected dog and normal canine bone marrow using a retroviral vector containing the human GALC cDNA. Successful treatment of this canine model will lead to studies in some humans with GLD. PMID- 9987922 TI - Frequency of the codon 807 mutation in the cGMP phosphodiesterase beta-subunit gene in Irish setters and other dog breeds with hereditary retinal degeneration. AB - Rod-cone dysplasia 1 (rcd1) in Irish setters is caused by a nonsense mutation in the cGMP phosphodiesterase beta-subunit gene (PDE6B). We examined the frequency of the mutant allele in the Irish setter population and determined if the defect is present in dogs of other breeds which are affected with other inherited photoreceptor diseases. Between 1994 and 1997, samples were obtained from 436 clinically normal Irish setters, a red wolf, and dogs from 23 different breeds. The mutation in codon 807 of PDE6B was detected in genomic DNA by heteroduplex analysis, allele-specific PCR, or restriction enzyme digestion. Of the 436 samples from clinically normal setters, 34 contained the mutation in one of the two PDE6B alleles (carrier rate = 7.8%). In contrast, the same mutation was not found in the red wolf or dogs of other breeds affected with PRA or inherited photoreceptor diseases. The high percentage of tested carriers, however, is not representative of the number of carriers in the population since some dogs tested were closely related and did not represent a random sample of the Irish setter breed. PMID- 9987923 TI - Markers within the regulatory region of the growth hormone receptor gene and their association with milk-related traits in Holsteins. AB - We studied sequence variations in the regulatory region of the bovine growth hormone receptor gene. A polymerase chain reaction (PCR)-based method for detecting AluI, AccI, and StuI restriction fragment length polymorphisms (RFLPs) in the 5' flanking region of the bovine growth hormone receptor gene was developed and tested for association with milk-related traits in Holstein bulls. Allele frequencies of the polymorphisms in two groups of Holstein progeny-tested bulls born from 1950 to 1970 and in the 1980s, respectively, were estimated. The allele frequency of the AluI(-) allele was 0.63 and 0.42 in the bulls from 1950 to 1970 and in the 1980s, respectively. The frequency of the StuI(-) allele was 0.14 and 0.07 in the two respective bull groups. Allele frequency for AccI(-) allele was about 0.22 in both bull groups. The differences in allele frequencies for the AluI polymorphism in the two bull groups were significantly different (P < or = .005). The AluI(+/+) bulls had a higher estimated breeding value (EBV) for fat (P < or = .016) than AluI(-/-) bulls. The average effect of allele substitution for the AluI polymorphism was +/- 8 for fat EBV. The AluI polymorphism could be further evaluated for use in marker-assisted selection in dairy cattle. PMID- 9987924 TI - Identification, inheritance, and linkage of B-G-like and MHC class I genes in cranes. AB - We identified B-G-like genes in the whooping and Florida sandhill cranes and linked them to the major histocompatibility complex (MHC). We evaluated the inheritance of B-G-like genes in families of whooping and Florida sandhill cranes using restriction fragment patterns (RFPs). Two B-G-like genes, designated wcbg1 and wcbg2, were located within 8 kb of one another. The fully sequenced wcbg2 gene encodes a B-G IgV-like domain, an additional Ig-like domain, a transmembrane domain, and a single heptad domain typical of alpha-helical coiled coils. Patterns of restriction fragments in DNA from the whooping crane and from a number of other species indicate that the B-G-like gene families of cranes are large with diverse sequences. Segregation of RFPs in families of Florida sandhill cranes provide evidence for genetic polymorphism in the B-G-like genes. The restriction fragments generally segregated in concert with MHC haplotypes assigned by serological typing and by single stranded conformational polymorphism (SSCP) assays based in the second exon of the crane MHC class I genes. This study supports the concept of a long-term association of polymorphic B-G-like genes with the MHC. It also establishes SSCP as a means for evaluating MHC genetic variability in cranes. PMID- 9987925 TI - Comparative linkage maps for the mosquitoes (Culex pipiens and Aedes aegypti) based on common RFLP loci. AB - We report construction of a comparative linkage map for the mosquito (Culex pipiens) based on restriction fragment length polymorphisms (RFLPs) using cDNA clones from Aedes aegypti as probes to Southern blots of Cx. pipiens genomic DNA. Seventy-one cDNA clones were screened for hybridization and genetic diversity among three Cx. pipiens strains. Fifty-two of 71 cDNA clones, isolated from and previously mapped in Ae. aegypti (73.2%), were hybridized under high-stringency conditions with Cx. pipiens genomic DNA. Thirty-four clones (47.9%) reflected strain-specific polymorphisms. The map consists of 21 cDNA markers that identify 22 loci covering 165.8 cM. The loci mapped in Cx. pipiens cover 7.1 cM on chromosome 1, 80.4 cM on chromosome 2, and 78.3 cM on chromosome 3. Linkage relationships of the RFLP markers for chromosome 1 in Cx. pipiens are the same as chromosome 1 in Ae. aegypti, indicating that chromosome 1 is highly conserved between the two species. The comparative RFLP linkage maps for chromosomes 2 and 3 in Cx. pipiens and Ae. aegypti reflect apparent whole-arm translocations. RFLP markers for chromosome 2 in Ae. aegypti identified homologous loci on one arm of chromosomes 2 and 3 in Cx. pipiens, and RFLP markers for chromosome 3 in Ae. aegypti identified homologous loci on the opposite arms of chromosomes 2 and 3 in Cx. pipiens. PMID- 9987926 TI - Cytochrome b gene haplotypes characterize chromosomal lineages of anoa, the Sulawesi dwarf buffalo (Bovidae: Bubalus sp.). AB - Partial mitochondrial cytochrome b gene sequences reveal two deeply differentiated mtDNA lineages in anoa dwarf buffaloes (Bubalus depressicornis) from the studbook herd in European zoos. Three matrilinear lineages of lowland anoas (depressicornis type) contributed three rather similar sequence haplotypes, but one remarkably distinct haplotype was observed exclusively in mountain anoas (quarlesi type) descended from one founder female. The carriers of the distinctive mtDNA haplotype were also distinguished by several chromosomal and phenotypic peculiarities too. The differentiation between the mtDNA lineages of anoa approached or even surpassed the genetic divergence between some uncontested species of wild cattle. The depth of this haplotype divergence in anoas is discussed against the background of the phylogenetic age of these paleoendemic inhabitants of a predator-free island refugium, Sulawesi, who are among the most plesiomorphic living bovines. The studbook breeding of captive anoas as a safeguard against extinction might profit from such population genetic markers. These cytochrome b gene sequences were unable to resolve the phylogeny of nine bovine taxa robustly, except the divergence of Bubalus, Synceros, Bison, and Bos (sensu lato) genera. PMID- 9987927 TI - Feline adult beta-globin polymorphism reflected in restriction fragment length patterns. AB - Adult domestic cats (Felis catus) appear to have the most polymorphic beta-globin system of any species. Reversed-phase high-performance liquid chromatography (RP HPLC) revealed one alpha-chain and six different beta-globin chains. Each cat may have one to four different beta-globins, and a total of 17 different beta-globin patterns were identified. Based on family studies, a beta-globin gene region with two linked beta-globin gene loci and two to five alleles was proposed. In order to further define the molecular basis of this polymorphism we performed Southern blot analysis of the beta-globin gene region from 25 cats with 13 different HPLC patterns. Genomic DNA was digested with five restriction endonucleases (BamHI, BglII, EcoRI, HindIII, and PstI) and blots were hybridized with a human beta globin probe. Restriction fragment length polymorphisms (RFLPs) with one to five fragments of 2.2-23 kb in size were found with BglII, EcoRI, HindIII, and PstI. Cats with specific HPLC beta-globin patterns had a unique DNA restriction pattern. The similarly sized BamHI and HindIII fragments of 4.6 kb suggest the presence of two closely linked genes. Furthermore, family studies suggest an autosomal codominant mode of inheritance of the beta-globin chains with seven haplotypes. Thus the RFLP data analyzed in the context of the HPLC haplotypes provide evidence at the DNA level for a feline beta-globin gene region with two closely linked gene loci and two to five alleles. PMID- 9987928 TI - Parentage and kinship studies in an obligate brood parasitic bird, the brown headed cowbird (Molothrus ater), using microsatellite DNA markers. AB - Recent studies suggest that single-locus microsatellite DNA markers have the potential to unambiguously resolve parentage among individuals in natural populations where maternity is known. However, their power for determining parentage when neither parent is known is unclear. Here we investigate the usefulness of microsatellite DNA markers to determine parentage in a brood parasitic bird, the brown-headed cowbird (Molothrus ater), where, for a given offspring, no a priori knowledge of either parent is available. Seven polymorphic microsatellite DNA markers isolated from brown-headed cowbirds and yellow warblers (Dendroica petechia) were used to genetically characterize an individually marked breeding population of male and female cowbirds at Delta Marsh, Manitoba. Forty-four males, 21 females, and 61 cowbird chicks were genotyped at seven loci using DNA amplified from blood and tissue samples. The mean exclusion probabilities pooled across all seven loci were 0.9964 for males and 0.9948 for females. Two null (non-amplifying) alleles at one locus were discovered and accounted for by constructing alternate nonoverlapping primer sets. Exclusion analyses performed using all individuals determined both paternity and maternity for 43 chicks and paternity only for 4 chicks. Another microsatellite locus was then used to determine paternity for three additional chicks. Relatedness analyses placed 12 of the 18 remaining chicks not assigned both maternity and paternity into four unique full sibling groups. Overall, 90.16% (55 of 61) of all offspring examined were placed into distinct parent/sibling groups, demonstrating that this marker set is extremely useful for parentage studies in this species. PMID- 9987929 TI - Assisted suicide of a selfish gene. AB - Medea (M) factors and the hybrid incompatibility factor (H) are involved in two incompatibility systems in flour beetles that were previously thought to be independent. M factors are a novel class of selfish genes that act by maternal lethality to nonself. The H factor causes the death of hybrids with a paternally derived H gene and previously uncharacterized maternal cofactors. We now find that M factors exhibit their selfish behavior only in the absence of the H factor. Furthermore, we show that the previously uncharacterized maternal cofactors required for H-associated hybrid inviability are identical to M factors. We propose that incompatibility between H strains and M strains is due to suppression by the H factor of the self-rescuing activity of the lethal M genes. This interaction has the effect of converting M elements from selfish into self-destructive or "suicidal" genes. M factors are globally widespread, but are conspicuously absent from India, the only country where the H factor is known to occur. Such a mechanism could prevent the spread of selfish M elements by establishing an absolute barrier to hybridization in the boundary between M and non-M zones. PMID- 9987930 TI - The yellow variegated mutant of Arabidopsis is plastid autonomous and delayed in chloroplast biogenesis. AB - The yellow variegated mutant of Arabidopsis thaliana is characterized by bright yellow true leaves that turn green- and white-sectored as leaf development proceeds. Variegation is due to the action of a nuclear recessive gene. Whereas cells in the green sectors contain morphologically normal chloroplasts, cells in the yellow and white sectors are heteroplastidic and contain plastids with rudimentary lamellar structures, as well as some normal-appearing chloroplasts. This indicates that plastids in yellow variegated are affected differently by the nuclear mutation (the mutant is "plastid autonomous"). Genetic analyses have revealed that yellow variegated is an allele of the var2 locus, and that defective plastids are not maternally inherited. The traits of plastid autonomy and lack of maternal inheritance of the plastid defect set var2 apart from other nuclear gene-induced variegations and define a novel class of variegation mutant. The primary lesion in var2 probably does not involve a blockage in the pathways of pigment biosynthesis. Under high temperatures or low light conditions, plant growth is retarded and mutant plants are nearly all-green. Considered together, our data suggest that var2 is delayed in chloroplast biogenesis. We suggest that the stochastic pattern of variegation in the mutant may be due to an interplay of factors that regulate var2 gene expression and factors that mediate rates of cell and plastid division. Plastids with a critical threshold of the partially functional var2 protein are green, while plastids containing less than the threshold of var2 activity are white. PMID- 9987931 TI - Microsatellite diversity in captive bottlenose dolphins (Tursiops truncatus). AB - The utility of microsatellites for managing captive Tursiops truncatus was investigated. Specifically the level of genetic diversity among the loci examined and their usefulness for resolving paternity was assessed. Overall a relatively low level of genetic variation was found among captive dolphins. In addition, a high percentage of common alleles was found among dolphins belonging to different morphotypes (inshore versus offshore). The implications of these findings are discussed and suggestions are given for the use of genetic markers in captive propagation programs for T. truncatus. PMID- 9987932 TI - The "spotted" locus maps to bovine chromosome 6 in a Hereford-Cross population. AB - The spotted locus is responsible for several phenotypically distinguishable piebald patterns in cattle, including Hereford, or white face (SH), lineback (SP), and recessive spotting (s), in addition to nonspotted (S+). In a backcross mapping population, the S locus has been mapped by genetic linkage to bovine chromosome 6, between microsatellite markers BM4528 and EL03. This region corresponds comparatively to a region on mouse chromosome 5 which houses several coat color mutations, among which homology is possible with Hardy-Zuckerman 4 feline sarcoma viral oncogene homologue (Kit), patch (Ph), and rump white (Rw). Mutations at these loci resemble mutations at the bovine S locus in both phenotype and mode of inheritance. Data are presented which show genetic linkage between the bovine S locus and microsatellite markers on chromosome 6. Candidate genes for the bovine S locus are discussed. PMID- 9987933 TI - Hybridization between sika deer (Cervus nippon) and axis deer (Axis axis). AB - We report an incidence of hybridization from natural mating between sika deer (Cervus nippon) and axis deer (Axis axis). A female exhibiting physical characteristics intermediate between the two species was born on a Tennessee deer farm sometime in 1995. Gel electrophoresis of three blood proteins (TF, HBB, and SOD) from the putative hybrid, the putative sika deer sire and three axis deer hinds from the herd (not necessarily including the dam) initially verified that hybridization had occurred. Q-banded karyotypes further identified the offspring as a hybrid (2n = 67) between sika deer (2n = 68) and axis deer (2n = 66). Fertility of the hybrid remains to be assessed, although it is now of reproductive age. PMID- 9987934 TI - Development and characterization of genetic mapping resources for the turkey (Meleagris gallopavo). AB - The development and partial characterization of turkey genomic libraries enriched for TG, GAT, and CCT simple sequence repeats (SSR) are described. The primary library, established using conventional methods, was enriched for each of the three SSR by single-primer polymerase chain reaction (PCR). The three enriched libraries were screened by standard hybridization and washing protocols under moderate to high stringency conditions. The utility of a fraction of the markers was evaluated based on the polymorphism of PCR-amplified products in a backcross reference DNA panel. The panel consisted of genomic DNA samples from three backcrossed families developed from a cross of a wild male turkey to three inbred Orlopp line C females. A total of 181 sequences from positive clones have been characterized and deposited in GenBank. About 60% of the 60 primer pairs designed from SSR-containing sequences detected polymorphism in the reference DNA panel. The turkey genomic DNA reference panel, the enriched libraries, and the markers described here provide an opportunity to begin to characterize the turkey genome and to develop a useful public genetic map for this economically important species. PMID- 9987935 TI - The mitochondrial genome of allotetraploid cotton (Gossypium L.). AB - Knowledge of patterns of organellar inheritance are crucial for analyses of organellar genetics and population or phylogenetic analyses based on organellar genes. While it has previously been shown that chloroplast DNA is maternally inherited in cotton (Gossypium L.), no, studies have assessed the mitochondrial genome complement of the allotetraploid species of cotton or addressed inheritance of mitochondrial DNA. In this article we report Southern hybridization analyses that indicate that the AD-genome allotetraploid species have an A-genome-like mitochondrial genome and provide evidence that mitochondrial genomes are also maternally inherited in cotton. PMID- 9987936 TI - [Use of heparin-coated "Jo Stent M" in patients with ischemic heart disease: first results]. AB - The aim of the present study was to make a clinical and angiographic assessment of early outcomes of the use of heparin-coated new "Jo Stents M". The Study comprised 41 patients who were implanted a heparin-coated new "Jo Stent M". There was an immediate success in 45 (97.6%) of 46 cases, the optimal angiographic and suboptimal (the maximum residual stenosis (13%)) results being achieved in 43 (93.4%) and 2 (4.4%) cases, respectively. The first success of the procedure was 97.8%. Due to acute stent thrombosis, acute occlusion with evolving myocardial infarction occurred in 1 (2.4%) patient. Following the procedure, the mean proportion of the stenotic diameter was (-5.8 +/- 6)%. After the procedure, the minimum stenotic diameter with the mean due diameter of 2.9 +/- 0.5 mm was 3.0 +/ 0.2 mm. The procedure-induced diameter increase was 2.1 +/- 0.5 mm. The total number of lateral branches involved in the stenting area was 11 (100%), 2 (18.2) of them closed after stent implantation. Two branches came into the stenting area in 1 (2.4%) case. At discharge, angina pectoris was absent in 30 (74%) patients. The heparin-coated "Jo Stent M" are effective and safe in treating patients with various clinical and angiographic manifestations of coronary atherosclerotic lesions. PMID- 9987937 TI - [Outcomes of balloon coronary angioplasty of bifurcation stenoses in patients with ischemic heart disease]. AB - The study included 322 patients with bifurcation lesion of the coronary bed who had angioplasty by the conventional procedure by employing one balloon. The authors analyze whether there is a correlation of balloon coronary angiographic findings with the following X-ray morphological characteristics: the origin of a lateral branch from the stenotic segment of the coronary artery, that of the branch at a distance of no more than 10 mm proximal or distal to stenosis, the angle of branch origin. Based on the findings, it was concluded that the origin of the branch from the stenotic segment is a factor that limits an angiographic success of dilatation of the great coronary vessel. The origin of the branch 10 mm proximal or distal to stenosis does not affect the angiographic success of the procedure. The risk factors of lateral branch lesion include the origin of the branch from a stenotic segment, an angle of branch origin of over 45 degrees. PMID- 9987938 TI - [Present day radiation diagnosis of upper stomach neoplasms]. AB - The paper analyzes over 3000 diagnosed gastric carcinomas. In the author's opinion, a drastic rise in the incidence of carcinomas of the upper stomach (as high as 60-65%) and the change in its anatomy common to gastric cancer- predominance of diffuse (endophytic) forms require a substantial correction of the present approaches to its detection. The paper gives the main points of radiation diagnosis (classic X-ray study, double contrasting, CT) for endophytic carcinomas at this site. In the author's opinion, nearly, as a rule, endoscopically diagnosed carcinomas of the lower esophagus and frequently involvement of the midesophagus are intramural carcinomas of the upper stomach with infiltration swiftly affecting the esophagus. The author considers radiation therapy to become a main method for detection of upper gastric carcinoma. He thinks that the active use of radiation techniques will also substantially expand diagnostic possibilities in these gastric carcinomas and will choose the most optimum plan of their surgical treatment. PMID- 9987939 TI - [Interventional radiology for chronic hemorrhoids complicated by hemorrhage]. AB - Based on the concept of the occurrence and development of hemorrhoids from the abnormally changed groups of cavernous bodies of the submucous membrane of the rectal transitional area, the authors used selective dearterialization of hyperplastic cavernous tissue that is simultaneously internal hemorrhoids. The essence of the new treatment is superselective X-ray endovascular catheterization of the superior hemorrhoidal artery and embolization of its distal branches which supply blood to rectal cavernous body. The outcomes of 337 Milligan-Morgan hemorrhoidectomies and 49 X-ray endovascular embolizations of the superior hemorrhoidal artery were analyzed in patients with chronic hemorrhoids complicated by hemorrhages. Emphasis is laid on the advantages of X-ray endovascular occlusion of the superior hemorrhoidal artery over conventional treatment. PMID- 9987940 TI - [Magnetic resonance Imaging in the diagnosis of hemophilic lesions of joints]. AB - A complex clinical, X-ray, and magnetic resonance tomographic study of 327 joints was made in 114 patients with different forms of hemophilic arthropathy. The diagnostic potentialities of MRI were defined and the MRI symptoms of hemophilic arthropathy, including degeneration of the articular cartilage, meniscus, ligaments, proliferation of the synovial membrane, fibrosis, blood accumulation, and hemosiderosis were revealed. Comparative analysis of the X-ray and MRI imaging findings of the joints at different stages of hemophilic arthropathy has shown that MRI has advantages in diagnosing acute and chronic hemarthrosis, moderate hemophilic osteoarthrosis as it can reveal abnormal processes in the X ray negative structures of joints. PMID- 9987941 TI - [Current methods of radiation therapy in patients with prostatic cancer: subtotal body radiation, local hyperthermia]. AB - The paper deals with the preliminary data of treatment of patients with prostatic cancer by using unconventional methods of radiation therapy (RT), such as subtotal radiation of the body (STRB) and thermoradiation treatment (TRT). Out of 72 patients receiving RT, 16 and 8 had STRB and TRT, respectively. Systemic and local drug therapies were made to prevent radiation reactions and injuries. In all cases, STRB and TRT showed a significant objective and subjective effect. To evaluate the long-term results of treatment needs further studies. PMID- 9987942 TI - [Clinical observation of mediastinal giant teratoma]. PMID- 9987943 TI - [Image deformation resulting from panoramic zonography of different facial cranial regions]. PMID- 9987944 TI - [Duodenal imaging during transabdominal ultrasound study]. PMID- 9987945 TI - [Current aspect of chronic gastritis complex diagnosis]. PMID- 9987946 TI - [Ultrasound techniques of diagnosis in treatment in modern medicine]. PMID- 9987947 TI - [New non-ionic monomeric and dimeric contrasting agents in radiology]. PMID- 9987948 TI - [Engineering base for radiation diagnosis]. PMID- 9987949 TI - [The Institute of Rheumatology is 40 years old: results and prospects]. PMID- 9987950 TI - [Institute of Rheumatology and progress of antirheumatic therapy]. AB - The paper deals with the achievements of the Institute of Rheumatology in antirheumatic therapy, among them there are methods of objective assessment of antirheumatic drugs, the first use of antimalarials in the treatment of chronic rheumatic fever, discovery of immunodepressive properties of these drugs, specification of the mechanism of action of several NSAIDs. Antilymphocytic globulin, salazopyridazine and the alkylating drug dopan were used for the first time in therapy of rheumatic diseases. Administration of the most potent NSAIDs diclofenac or indomethacin to patients with acute rheumatic fever proved to be as effective as prednizolone. Special attention is paid to the combination treatment of rheumatoid arthritis with NSAIDs. The concurrent administration of aurannofin and methotrexate was shown to cause a more rapid development of clinical improvement than monotherapy with either drug. A combination of gold aurothiomalate and hydroxychloroquine and that of low doses of D-penicillamine and cyclophosphamide had no advantages over monotherapy. Revealing the therapeutical potential of antibodies to interferon-gamma in the treatment of rheumatic arthritis and psoriatic arthritis was the most important achievement of recent years. These studies open new vistas for anticytokine treatment of rheumatic diseases. PMID- 9987951 TI - [Role of the Institute of Rheumatology in formation and development of State controlling system of rheumatic diseases]. AB - The paper gives a brief account of the stages of formation and development of rheumatological care in the country, which are closely related to the researches and practical activities of the Institute of Rheumatology. PMID- 9987952 TI - [Clinical immunology in rheumatology]. AB - When the Institute of Rheumatology, USSR Ministry of Health, was founded, its first director Academician A. I. Nesterov set up an immunological laboratory to attack the problems of immunodiagnosis and pathogenesis of rheumatism. Since 1958 studies of systemic diseases of connective tissue and autoimmunity under the supervision of Prof. V. A. Nasonova have been under way. Radioisotopic, enzyme immunofluorescence diagnostic assays for antinuclear antibodies (ANA) have been developed. Jointly with Czechoslovakia and the USA, the Institute of Rheumatology standardized the definitions of ANA. The laboratory have proposed the guidelines of the USSR Ministry of Health for immunodiagnosis of rheumatic diseases (RD). For immunodiagnosis, immunofluorescence, enzyme immunoassays, gel precipitation, back electrophoresis, radial immunodiffusion are widely used to measure the concentrations of anticardiolipin antibodies, mitochondrial antibodies, neutrophilic antibodies. The clinical and immunological subtypes of diffuse connective tissue diseases have been identified and characterized. Mixed connective tissue disease, poststreptococcal arthritis are described. The laboratory equipment for polymerase chain reaction permits DNA diagnosis. PMID- 9987953 TI - [Epidemiology of rheumatic diseases in historical aspect]. AB - The paper summarizes the results of the long-term study of the epidemiology of rheumatic diseases, which has been carried out by the Institute of Rheumatology. The main directions of the study are the development and improvement of diagnostic criteria, the prevalence and incidence of rheumatic diseases among urban and rural populations, at industrial enterprises, in different ethnic groups, genetic and environmental risk factors, disability, the development and introduction of preventive and rehabilitative programmes of drug therapy, etc. A number of combined national programmes was carried out. The paper presents specific results of their implementation. PMID- 9987954 TI - [Scientific bases of medical examinations of patients with rheumatic diseases]. AB - The 40-year experience of the Institute of Rheumatology has shown that follow-up in rheumatic diseases is the necessary method of management of patients with rheumatic diseases since it is the method that makes it possible to control the progression of disease and provide long-term safe treatment with glucocorticoids, cytotoxics, and other antirheumatic drugs which are now widely used in rheumatological care. Medical examination mainly made in rheumatism caused a substantial reduction in the number of relapses. Since the 1960s, intensive and scientifically grounded studies in medical examinations for other rheumatic diseases have promoted more prolonged longevity and better working fitness in the vast majority of patients. Thus, a long-term follow-up of over 600 patients with exanthematous lupus erythematosus made it possible to detail its clinical picture and to develop the therapeutical programmes that control the progression of the disease in 93% of the patients who had been incurable before. In rheumatoid arthritis, the follow-up of large groups of patients by using the computer database has enabled the researchers to develop a mathematically accurate method for prediction of the progression of disease by employing the integral parameter- the index of severity, as well as to reveal a number of important regularities of treatment. A follow-up of patients with reactive arthritis, Bekhterev's disease, systemic scleroderma, and other rheumatic diseases is shown to be of great importance. PMID- 9987955 TI - [Development of studies on problem of infectious arthritis at the Institute of RHeumatology, Russian Academy of Medical Sciences in 1970 to 1990]. AB - The paper presents information on the studies on the elucidation of the etiopathogenetic role of Chlamydia and Yersinia infections in reactive arthritis, which have been made at the Institute in the past decades. Among them it mentions the first experiments and subsequent findings of detection of both Chlamydia and DNA in joint tissues in urogenic arthritis, those of identification of altered minor forms of this microbe in chronic types, which mimic in vitro persistent Chlamydia infection. The clinical experience gained by the Institute in treating Chlamydia-induced urogenic arthritis with high-dose antibiotics is reported. In addition to detailed studies of the clinical manifestations and outcomes of Yersinia-induced arthritis, long-term follow-ups have examined an association of clinical and serological manifestations with HLA B27 carriage; it is suggested that there is a partial similarity between this antigen and Yersinia antigens. Pronounced changes have been found in the mucosa of the intestine and its microflora in enterogenous reactive arthritis and a treatment with bifidum containing drugs proposed. A variety of clinical and serological manifestations of Lyme borreliasis detected in the endemic areas of Russia is described. The specific features of rheumatological manifestations of this disease are comparable with those observed in the USA and Europe. PMID- 9987956 TI - [Forty years study of systemic scleroderma (data of Institute of Rheumatology, Russian Academy of Medical Sciences)]. AB - The basic stages and the results of 40-year studies of systemic scleroderma (SSD) at the Institute of Rheumatology, Russia Academy of Medical Sciences, are given. The goal-oriented studies of the systemic, peripheral, and visceral manifestations of the disease, which were undertaken in the 1960s basically altered our insight into the disease. Subsequently the diagnostic signs of the disease were developed, which substantially improved the diagnosis of SSD. Long term studies examined the evolution of SSD and identified three major types of its course: acute, subacute, and chronic, which differ in the rapidity of progression of a pathological process, the pattern of clinical and morphological manifestations and prognosis, as evidenced by survival rates. The identified types of the course (n = 3) and clinical forms (n = 5) formed the basis for the Russia classification of SSD. Studying the pathogenesis of the disease mainly in the context of the mechanisms of formation of fibrosis and impaired microcirculation, as well as its clinical heterogeneity served as the basis for developing pathogenetic therapy regimens by differentially using disease modifying agents and other therapeutical complexes. At present, the Institute of Rheumatology has accumulated unique experience in studying and following over 1500 patients with SSD and related diseases. There is a rise in the sclerodermal group of diseases, cross-over and combined forms of SSD along with great progress in the diagnosis and treatment, which enhances the quality of life of patients with SSD and prognosis in them. PMID- 9987957 TI - [Synchronous intensive treatment for patients with systemic lupus erythematosus having poor life prognosis]. AB - Synchronous intensive treatment (SIT) involving two-stage programmed use of pulse therapy (PT), plasmapharesis (P) or hemosorption with methylprednisolone and cyclophosphamide was performed in 56 patients with systemic lupus erythematosus (SLE). All the patients were found to have a combination of factors showing a poor life prognosis: the onset of SLE in adolescence or youth (52%), nephritis (70%), arterial hypertension (54%), cerebropathy (50%), generalized vasculitis (34%), cryoglobulinemia (66%). After a year therapy, remission and the minimum progression were observed in 19.6 and 53.6%, respectively. The highest effect of SIT was found in the patients with SLE of duration of under a year and with the highest progression. A long-term follow-up that lasted 78 +/- 24 months revealed persistent improvement, the minimum activity and remission in 71% of patients. The synchronous programmed use of P and PT produces a rapid and effective impact on clinical and laboratory manifestations and improves life prognosis in patients with SLE. PMID- 9987958 TI - [Intravenous immunoglobulin in combined therapy for children with juvenile rheumatoid arthritis (evaluation of therapeutical efficiency and factors that influence them)]. AB - The study was based on the follow-up of 20 patients with systemic juvenile rheumatoid arthritis who received intravenous immunoglobulin. The study comparatively analyzed the efficiency of the therapy alone and in combination with steroids. The immunoglobulin was shown to have positive effects on both articular and extraarticular manifestations of the disease particularly in a group of children untreated with corticosteroids. The duration of the disease did not affect the therapeutical properties of immunoglobulin. PMID- 9987959 TI - [Genetic aspects of rheumatic diseases]. AB - The paper presents the results of the long-term studies of the pattern of hereditary predisposition to rheumatism, rheumatoid arthritis (RA), ankylosing spondyloarthritis (AS), osteoarthrosis which have been conducted at the Institute of Rheumatology, Russian Academy of Medical Sciences. It gives data on the type of inheritance of these diseases, the affliction heritability ratio, the penetrance of three genotypes within the model of an autosomal one-allele locus (SAL-2) for rheumatism and RA. The contribution of additive and dominant components in the determination of rheumatism and RA, the results of tests of their genetic heterogeneity, associations with HLA antigens are assessed. The paper outlines the results of tests of the candidate genes COLIA2, TCRB, TCRD as major RA predisposition genes via analysis of adherence and DNA polymorphism. PMID- 9987960 TI - [Dyslipidemias and autoimmune diseases]. AB - The paper summarizes the results of over 30-year studies dealt with dyslipidemias and autoimmune diseases. The teaching of the antiphospholipid syndrome (APS) has aroused interest in the problem. The experience gained shows changes in the blood cholesterol transport system. Patients with systemic lupus erythematosus (SLE) have higher levels of low density lipoprotein cholesterol and lower concentrations of high density lipoprotein (HDL) cholesterol, apolipoprotein A than the controls. The quantitative and qualitative changes in particles result in decreased acceptance of cholesterol from the membrane of a cell and tissues, which promotes the development of vascular diseases. Lipoprotein (a) may be an additional risk factor for thrombosis chiefly of coronary arteries, in patients with SLE and APS. Increased levels of oxidized low density proteins having atherogenic activity were found mainly in patients with SLE. The use of corticosteroids causes the changes in the spectrum of blood lipids, which together with other factors (thrombosis, vasculopathy, thrombocytopenia, etc.) create good conditions for the development of atherosclerosis, which determines the necessity of correcting the parameters of blood lipid transport not only to prevent vascular disorders but to improve the general life prognosis in SLE patients. PMID- 9987961 TI - [Early rheumatoid synovitis and its evolution]. AB - The clinical and morphological evidence of rheumatoid synovitis of 3 months to 5 years duration was analyzed. Its early lesions were characterized by angiomatosis, vasculopathy, and proliferation of synoviocytes and fibroblasts. Protein infiltrates contained IgG and C3 complement. Herpes simplex was detected in the vessels and synoviocytes. Structural changes may be explained by immune mechanisms and by infectious agents as well. Chronic inflammation, vasculitis, and sclerosis were prevalent in late rheumatoid synovitis. Lymphoid follicles, macrophages, and endothelial proliferation can be markers for infectious persistence. PMID- 9987962 TI - [Rheumoorthopedics as an integral part of complex therapy of rheumatic diseases with joint involvement]. AB - The paper gives the results of conservative and surgical rehabilitation of patients over 38 years after the foundation of an orthopedic service at the Institute of Rheumatology. Conservative treatments for rheumatic diseases (RD) such as position treatment, formation of a correct stereotype, treatment of the cervical portion of the spine in rheumatic arthritis (RA) and osteoarthrosis derformans (OAD) are evaluated. The author's own experience involving over 5000 operations on the locomotor apparatus in RD, which permits assessment of the most common and successful operations, such as sinovectomy, arthroplasty, arthrodesis, endoprosthesis. Rheumoorthopedics is a part of complex rehabilitative treatment for RD as it enables one to infer actively at different stages of RD and to achieve high results in patients, including those who unresponsive to medical treatment. PMID- 9987963 TI - [Genetic analysis of pathogenic streptococci groups A and B]. AB - The study deals with the genetic mapping of chromosomal DNA of groups A (AS) and B (BS) pathogenetic Streptococci. Its stages are presented and considered. The maps of these microorganisms are compared. A collection of epidemic AS and BS was analyzed by employing pulsed field gel electrophoresis. AS and BS were found to show heterogeneity of DNA sequences and the common pattern of gene location on the chromosomes. PMID- 9987964 TI - [Hormones and auto-paracrine tumor growth regulators in osteogenic sarcoma]. AB - The paper analyzes the data of long-term studies made in the N. N. Blokhin Cancer Research Center, Russian Academy of Medical Sciences. The study dealt with androgen exchange, the baseline levels of serum sexual steroid hormones and their receptors in the tumor, the blood concentrations of the sexual steroids conjugated globulin and pituitary hormone, the metabolism of arachidonic acid, the expression of epidermal growth factor and its ligands, the amount of calmodulin, cAMP in the osteogenic sarcoma in 300 patients aged 14-56 years. Analyzing the findings suggests that there are some directions in studies, development, and practical introduction of new pathogenetic therapies of osteosarcoma, which are associated with the regulation of androgen exchange, the correction of the cyclooxygenase pathway of arachidonic acid, expression of receptors of epidermal growth factor and its ligands in the tumor. PMID- 9987965 TI - [Expression af early genes in memory mechanisms]. PMID- 9987966 TI - [Conceptual problems in the development of health resort science in Russia]. PMID- 9987967 TI - [The contribution of the scientists of the Military Medical Academy to the development of Russian physiotherapy and health resort science (on the 200th anniversary of the Military Medical Academy and the 70th anniversary of the Department (Course) of Physiotherapy and Health Resort Science of the Military Medical Academy)]. PMID- 9987968 TI - [A comparative analysis of the action of red and infrared laser radiation and ultrasound on the regeneration of locally irradiated skeletal muscle and on immune system function in the rat]. AB - The study was made of a regeneration ability of the rat skeletal muscle which had been mechanically injured and exposed to a 20 Gy irradiation, of the thymus and bone marrow condition after local exposure of the muscle to red and infrared laser radiation and ultrasound. These factors were found to stimulate regeneration of the injured soft tissues and to reduce cytogenetic damage to bone marrow cells in the irradiated zone under growing immunosuppression. The stimulation was most potent in prolonged exposure to the ultrasound. PMID- 9987969 TI - [The efficacy of psychotherapy with biofeedback in the rehabilitation of hypertension patients]. AB - 85 females with borderline mental disorders in essential hypertension were followed up for a month and 6 months after the treatment (hypotensive drugs + psychotherapy with biofeedback or hypotensive drugs only--45 patients and 40 controls, respectively). The addition of psychotherapy to hypotensive drugs contributed to a higher hypotensive effect, long-term improvement of psychic condition, more active attitude to the treatment process and psychic adaptation. Better quality of life was achieved. PMID- 9987970 TI - [The optimization of the arrangement of physiotherapeutic procedures based on the circadian dynamics of the cardiointervalographic indices]. AB - It was found that patients with neurological manifestations of spinal osteochondrosis had marked disturbances of diurnal biorhythms of cardiointervalography (CIG): wider amplitude and structural alterations. Administration of physiobalneoprocedures in the period between acrophase and batiphase brings normalization of biorhythms. If the procedures were given in the peak phase, the normalization was not achieved. Moreover, the biorhythms got worse in 75% of the patients. To optimize the regimen of physiobalneoprocedures in patients with neurological manifestations of spinal osteochondrosis it is valid to study diurnal pattern of CIG and administration of physiotherapeutic procedures in the time of change of the diurnal rhythm phases. PMID- 9987971 TI - [The action of potable mineral waters on reparative regeneration processes in the stomach]. AB - The analysis of the data obtained on effects of different drinking mineral waters on healing of experimental gastric ulcer has established different effects of the waters on the repair depending on chemical composition of the waters. PMID- 9987972 TI - [The effect of reflex muscle massage on the body regulatory processes of peptic ulcer patients with concomitant diseases]. AB - Compared to conventional treatment, the proposed method of deep reflex muscular massage for treatment of ulcer patients with associated diseases in combination with exercises for muscle strain, produce stronger positive changes in adaptive compensatory systems. This may result in prolongation of the remission and in a decreased number of recurrences of ulcer and associated gastrointestinal diseases. PMID- 9987973 TI - [The comparative effect of magnetic-laser irradiation of the liver and blood on bile release and composition in an experiment]. AB - The effects of transcutaneous magnetolaser radiation of the liver, blood alone and in combination on bile secretion and composition were studied in intact rats. Hepatocytes activation was noted in all the above variants. Magnetolaser impact on both the liver and blood intensified bile production under less total density of the radiation energy. Bile and direct bilirubin secretion increased. Excretion of bile acids enhances selectively, while that of cholesterol diminished. There may be mutual potentiation, summing and selectivity of the effects arising in combined magnetolaser radiation of the liver and blood. PMID- 9987974 TI - [The efficacy of treating patients with allergic diseases at a health resort with a gastroenterologic profile]. AB - 45 allergic patients were treated in gastrointestinal sanatorium. Balneological and speleo modalities were employed. The clinical symptoms and humoral immunity indicated high efficacy of such treatment. The complex is recommended for introduction in gastrointestinal sanatoria. PMID- 9987975 TI - [Physiotherapy methods in the rehabilitation of children with gastroduodenal pathology]. AB - 100 children with chronic gastroduodenitis and ulcer received laser treatment and dalargin electrophoresis. The controls received conventional chemotherapy. The treatments demonstrated similar effectivity as shown by clinical, endoscopic and special examinations, against Helicobacter pylori, in particular. PMID- 9987976 TI - [Carbon dioxide baths in the combined health resort treatment of children with autonomic vascular dystonia]. PMID- 9987977 TI - [The dynamics of the tissue oxygen regimen in patients with circulatory encephalopathy under the influence of oxygen baths]. PMID- 9987978 TI - [Interference therapy and radon baths in the combined treatment of patients with reflex cervicobrachial syndromes]. AB - Patients with cervicobrachialgic syndromes on interference therapy, exercise treatment, massage of the cervical collar region received balneotherapy. 42 of them took water baths, 39 took dry air radon baths. These complexes proved effective in cervicobrachialgic syndromes, the effect being slightly dependent on the clinical symptoms of the disease. PMID- 9987979 TI - [A differentiated approach to the choice of physiotherapy methods in trigeminal prosopalgia]. AB - 148 patients with trigeminal neuralgia, odontogenic neuropathies of the alveolar nerves, neuropathy of the main trigeminal nerves and their sensitive branches, neuropathic complications after alcoholization received individually selected physiotherapy in each prosopalgia in acute and subacute period. Adequate choice of physical factors and physiotherapy is dependent on careful examination of the patient with consideration of topical and pathogenetic features of the disease. PMID- 9987980 TI - [The morphofunctional validation of the use of vibration-traction for the correction of contractures of the joints]. AB - Experiments in modelling joint contracture have shown that vibrotracture with step-by-step frequency rise in one procedure and discrete rise in traction power in the course of procedures may correct joint contracture. Basing on these experimental findings, the authors have developed highly effective method of vibrotraction treatment of joint contractures (patent N 1804819). PMID- 9987981 TI - [The effect of massage on the neuromuscular apparatus and blood coagulating system of patients with chronic salpingo-oophoritis]. AB - 74 patients with chronic salpingo-oophoritis (CS) in remission were assessed as to effects of classic massage of the uterine and epoophoronic reflexogenic zones on clinical pattern of the disease, bioelectric activity of the abdominal muscles, spine and pelvis, blood coagulation. The combined massage produced a more potent effect on electric activity of the above muscles and blood coagulation than massage on a single area. It is better to start massage from the abdomen and continue in the lumbosacral area. PMID- 9987982 TI - [Kinesitherapy in the early rehabilitation of neurosurgical patients with bladder dysfunction]. AB - The authors review anatomical-functional features of different forms of urinary bladder dysfunction, offer kinesitherapy for patients with neurogenic dysfunction of the urinary bladder. Their experience with 52 neurosurgical patients who early after operation exercised according to the proposed method demonstrates a response in 83% of the patients due to activation of the existing and creation of the additional reflex component of micturation. PMID- 9987985 TI - [Trace elements and vitamins as activators of the adaptation reactions in combined health resort treatment]. PMID- 9987986 TI - Domestic violence in Japan. AB - Traditionally, domestic violence in Japan referred to children's physical and emotional violence against their parents. However, in recent years, the general public's awareness of and actions toward other types of domestic violence, especially violence against women and children, has increased. Following a brief description of filial violence and elderly abuse, both spousal abuse and child abuse are discussed in terms of their prevalence and cultural and historical backgrounds. The article concludes with current and future challenges in the intervention of violence, particularly against women and children, in the Japanese family. PMID- 9987983 TI - [New data on the size of the operational reserves of radon thermal springs at the Belokurikha deposit in the Altai]. PMID- 9987984 TI - [The use of magnesium-calcium carbonate mineral water in kidney diseases]. PMID- 9987987 TI - Domestic violence in Russia. AB - Reported incidence and frequency rates of domestic violence in Russia exceed Western figures by 4 or 5 times. Although a grassroots social services movement has emerged to provide services for victims and families, a number of historical and cultural influences unique to Russia present challenges with regard to the problem of domestic violence. These include a history of institutional oppression of women, arcane legal procedures, a shortage of housing and shelters, untrained medical professionals, and widespread misinformation and myths about domestic violence. This article documents incidence and prevalence of domestic violence, cultural and historical influences, legal issues, and specific challenges to ending domestic violence in Russia. PMID- 9987988 TI - Gonadotropin-releasing hormone neuronal system of the freshwater snails Helisoma trivolvis and Lymnaea stagnalis: possible involvement in reproduction. AB - Peptides of the gonadotropin-releasing hormone (GnRH) family are present in neural and nonneural tissues throughout the chordate phylum. Although GnRH peptides have been implicated in nonreproductive functions, their primary function is to control reproduction by regulating sexual behaviors and inducing gonadotropin hormone release from the pituitary. Evidence suggesting the presence of a similar peptide in the central nervous system (CNS) of the gastropod mollusc Helisoma trivolvis has recently been provided. In the present study, we examined the tissue distribution of the peptide and found that it is likely restricted to the nervous system. The neuronal system containing the endogenous GnRH-like peptide is described further and is shown, in part, to innervate the male reproductive tract. Immunostaining in the closely related snail, Lymnaea stagnalis, showed a conservation in the locations of some immunoreactive neurons. Notably, staining occurred in and adjacent to the lateral lobes of both snails. Because these lobes contain neurons involved in the stimulation of egg laying and GnRH staining occurred in additional areas in the Helisoma CNS that are involved in reproduction, we suggest that the endogenous GnRH-like peptide plays a role in regulating reproduction in freshwater snails. PMID- 9987989 TI - Spiny calretinin-immunoreactive neurons in the hilus and CA3 region of the rat hippocampus: local axon circuits, synaptic connections, and glutamic acid decarboxylase 65/67 mRNA expression. AB - We have used the Golgi method and Golgi electron microscopic techniques to analyze the axonal arborization and efferent connections of spiny calretinin immunoreactive neurons in the CA3 region and hilus of the rat hippocampal formation. In the hilus, the axons of spiny calretinin-immunoreactive neurons sent out numerous collaterals that arborized in the hilar region and the molecular layer. In the CA3 region, these axons extended mainly to the stratum radiatum and pyramidal layer but also to the stratum oriens and stratum lacunosum moleculare. Axonal varicosities were distributed widely throughout the axonal collaterals. Electron microscopic studies revealed that the axon terminals of spiny calretinin-immunoreactive neurons established synaptic contacts mainly with dendritic shafts. We next analyzed the expression of glutamic acid decarboxylase (GAD65/67) mRNAs in spiny nonpyramidal neurons that were identified by calretinin immunoreactivity. We found that spiny calretinin-positive neurons in the CA3 region and hilus of the rat hippocampal formation expressed the two isoforms of GAD: GAD65 and GAD67 mRNAs. These findings show that the spiny calretinin immunoreactive neurons of hippocampus give rise to local axonal arborizations, suggesting that they are inhibitory. PMID- 9987990 TI - Null mutation in shaking-B eliminates electrical, but not chemical, synapses in the Drosophila giant fiber system: a structural study. AB - Mutations in the Drosophila shaking-B gene perturb synaptic transmission and dye coupling in the giant fiber escape system. The GAL4 upstream activation sequence system was used to express a neuronal-synaptobrevin-green fluorescent protein (nsyb-GFP) construct in the giant fibers (GFs); nsyb-GFP was localized where the GFs contact the peripherally synapsing interneurons (PSIs) and the tergotrochanteral motorneurons (TTMns). Antibody to Shaking-B protein stained plaquelike structures in the same regions of the GFs, although not all plaques colocalized with nsyb-GFP. Electron microscopy showed that the GF-TTMn and GF-PSI contacts contained many chemical synaptic release sites. These sites were interposed with extensive regions of close membrane apposition (3.25 nm +/- 0.12 separation), with faint cross striations and a single-layered array of 41-nm vesicles on the GF side of the apposition. These contacts appeared similar to rectifying electrical synapses in the crayfish and were eliminated in shaking-B2 mutants. At mutant GF-TTMn and GF-PSI contacts, chemical synapses and small regions of close membrane apposition, more similar to vertebrate gap junctions, were not affected. Gap junctions with more vertebratelike separation of membranes (1.41 nm +/- 0.08) were abundant between peripheral perineurial glial processes; these were unaffected in the mutants. PMID- 9987991 TI - Regional and subcellular distribution of a neutral and basic amino acid transporter in forebrain neurons containing nitric oxide synthase. AB - The neutral and basic amino acid transporter (NBAT) facilitates sodium independent transport of L-amino acids in renal and intestinal epithelial cells and has been postulated to play a similar role in neurons. In previous studies, NBAT has been detected within enteric and brainstem autonomic neurons in a distribution similar to that of constitutive nitric oxide synthase (cNOS). Furthermore, L-arginine, the required precursor for nitric oxide synthesis, is an excellent NBAT substrate. Together, these findings suggest that NBAT may play a role in the regulation of nitric oxide synthesis, through the control of precursor availability. To gain insight into the potential physiological role of NBAT in central neurons, we used an antipeptide antiserum to examine the light and electron microscopic immunocytochemical localization of NBAT in the rat forebrain and to compare this distribution with that of cNOS. Immunolabeling for NBAT was detected within perikarya and dendrite-like processes that were most numerous in the frontal and cingulate cortex, the ventral striatum, the central amygdala, and the bed nucleus of the stria terminalis. Labeled varicose axonal processes were distributed most densely in the agranular insular cortex and the paraventricular nuclei of the thalamus and hypothalamus (PVH). Electron microscopy showed that immunogold labeling for NBAT was distributed along plasmalemmal and vacuolar membranes within somata, dendrites, and axonal profiles. Many of the NBAT-containing somata and dendrites contained detectable cNOS. Our results suggest that expression of NBAT may provide specific populations of cNOS-containing forebrain neurons with a unique mechanism for regulating somatodendritic synthesis of nitric oxide. PMID- 9987992 TI - Morphology, axonal projection pattern, and response types of tectal neurons in plethodontid salamanders. I: tracer study of projection neurons and their pathways. AB - In three salamander species (Hydromantes italicus, H. genei, Plethodon jordani), the tectobulbospinal and tectothalamic pathways and their cells of origin were studied by means of anterograde and retrograde biocytin and tetramethylrhodamine tracing. In plethodontid salamanders, five types of tectal projection neurons were identified. TO1 neurons have widefield dendritic trees that arborize in the layers of retinal afferents and form a neuropil in the superficial layer; axons constitute the crossed tectospinal tract. Dendrites of TO2 cells have the largest dendritic trees that arborize in the intermediate and deep layers of retinal afferents; axons constitute a lateral uncrossed tectospinal tract. TO3 cells have widefield dendritic trees that arborize in the deep layer of retinal afferents and in the layer of tectal efferents; axons constitute a superficial uncrossed tectospinal tract. TO4 cells have slender primary dendrites and small-field dendritic trees that arborize in the intermediate layers of retinal afferents; axons constitute another lateral uncrossed tectospinal tract. TO2, TO3, and TO4 cells also have ascending axons that run to the ventral and dorsal thalamus. TO5 cells have slender primary dendrites and small-field dendritic trees that extend into the superficial layers of retinal afferents; their fine axons constitute the bulk of the pathways ascending to the ipsilateral and contralateral thalamus. These morphological types of projection neurons and their ascending and descending axonal pathways closely resemble those found in frogs, reptiles, and birds. Their role in visual and visuomotor functions is discussed. PMID- 9987993 TI - Morphology, axonal projection pattern, and response types of tectal neurons in plethodontid salamanders. II: intracellular recording and labeling experiments. AB - In the plethodontid salamanders Plethodon jordani and P. glutinosus, the morphology and axonal projections of 140 tectal neurons and their responses to electrical optic nerve stimulation were determined by intracellular recording and biocytin labeling. Six types of neurons are distinguished morphologically. TO1 neurons have wide dendritic trees that arborize mainly in tectal layers 1 and 3; they project bilaterally to the tegmentum and contralaterally to the medulla oblongata. TO2 neurons have very wide dendritic trees that arborize mainly in layers 2 and 3; axons project bilaterally or unilaterally to the pretectum and thalamus and ipsilaterally to the medulla oblongata. TO3 neurons have very wide and flat dendritic trees confined to layers 3-5; some have the same axonal projection as TO2 neurons, whereas others have descending axons that reach only the level of the cerebellum. TO4 neurons have narrower dendritic trees that arborize in layers 2 and 3; they project to the ipsilateral pretectum, thalamus, and medulla oblongata. TO5 neurons have dendritic trees that arborize in layers 1 and 2 or 1-3 and project bilaterally or unilaterally to the pretectum and thalamus. TO-IN are interneurons, with a number of subtypes with respect to variations in dendritic arborization pattern. TO1-TO5 neurons generally have short latencies of 2-16 ms (average = 8.4 ms) at electrical optic nerve stimulation; first responses are always excitatory, often followed by inhibition. They are likely to be mono- or oligosynaptically driven by retinal afferents. TO IN interneurons have long latencies of 20-80 ms (average = 38.6 ms) and appear to receive no direct retinal input. With their specific dendritic arborization, consequent dominant retinal input, specific axonal projections, the different types of tectal projection neurons constitute separate ascending and descending visual pathways. Hypotheses are presented regarding the nature of the information processed by these pathways. PMID- 9987994 TI - Age- and sex-related differences in opioid receptor densities in the songbird vocal control system. AB - Avian vocal control regions of adult male songbirds contain opioid peptides and receptors, suggesting that opioids play a role in avian vocal behavior control. In a previous study, we found no difference in opioid receptor densities in singing versus nonsinging adult male dark-eyed juncos (Junco hyemalis), leading us to hypothesize that opioids are not involved in controlling song production. To assess whether opioids may be involved in other aspects of vocal behavior, we used quantitative in vitro autoradiography to compare mu and delta opioid receptor densities in vocal control regions of singing adult males with those of adult females and adolescent (about 3 months old) males and females. We found mu and delta receptors in all vocal control regions measured. Adolescents had significantly higher opioid receptor densities than did adults in area X (delta), robust n. of the archistriatum (delta and mu), and n. intercollicularis (mu), suggesting a developmental role for opioids in the vocal control system. Based on opioid roles in other animal models, we propose that opioids may be involved in song learning, auditory processing, and/or vocal control system development. PMID- 9987995 TI - Early retinal development in the zebrafish, Danio rerio: light and electron microscopic analyses. AB - The morphological differentiation of the zebrafish retina was analyzed by using light (LM) and transmission electron (TEM) microscopy between the time of initial ganglion cell differentiation (approximately 32 hours postfertilization; hpf) and shortly after the point when the retina appears functional (approximately 74 hpf), i.e., when all major cell types and basic synaptic connections are in place. The results show that the inner retinal neurons, like the photoreceptor and ganglion cells, differentiate first within the ventronasal region, and differentiation subsequently spreads asymmetrically into the nasal and dorsal regions before reaching the ventrotemporal retina. In addition, we show that the attenuation of the optic stalk occurs in parallel with ganglion cell differentiation between 32 and 40 hpf. The first conventional synapses appear within the inner plexiform layer simultaneously with the first photoreceptor outer segment discs at 60 hpf; functional ribbon triads arise within photoreceptor synaptic terminals at 65 hpf; and synaptic ribbons occur within bipolar cell axon terminals at the time larvae exhibit their first visual responses (approximately 70 hpf). Although development is initially more advanced within the ventronasal region between 50 and 60 hpf, development across the retina rapidly equilibrates such that it is relatively comparable within all quadrants of the central retina by 70 hpf. An area within the temporal retina characterized by tightly packed and highly tiered cones emerges with subsequent development. Retinal differentiation in the zebrafish corresponds with that generally described in other vertebrates and can be correlated with the development of visual and electroretinographic responses in the animal. PMID- 9987996 TI - Mossy fiber sprouting after recurrent seizures during early development in rats. AB - In some children, epilepsy is a catastrophic condition, leading to significant intellectual and behavioral impairment, but little is known about the consequences of recurrent seizures during development. In the present study, we evaluated the effects of 15 daily pentylenetetrazol-induced convulsions in immature rats beginning at postnatal day (P) 1, 10, or 60. In addition, we subjected another group of P10 rats to twice daily seizures for 15 days. Both supragranular and terminal sprouting in the CA3 hippocampal subfield was assessed in Timm-stained sections by using a rating scale and density measurements. Prominent sprouting was seen in the CA3 stratum pyramidale layer in all rats having 15 daily seizures, regardless of the age when seizures began. Based on Timm staining in control P10, P20, and P30 rats, the terminal sprouting in CA3 appears to be new growth of axons and synapses as opposed to a failure of normal regression of synapses. In addition to CA3 terminal sprouting, rats having twice daily seizures had sprouting noted in the dentate supragranular layer, predominately in the inferior blade of the dentate, and had a decreased seizure threshold when compared with controls. Cell counting of dentate granule cells, CA3, CA1, and hilar neurons, with unbiased stereological methods demonstrated no differences from controls in rats with daily seizures beginning at P1 or P10, whereas adult rats with daily seizures had a significant decrease in CA1 neurons. Rats that received twice daily seizures on P10-P25 had an increase in dentate granule cells. This study demonstrates that, like the mature brain, immature animals have neuronal reorganization after recurrent seizures, with mossy fiber sprouting in both the CA3 subfield and supragranular region. In the immature brain, repetitive seizures also result in granule cell neurogenesis without loss of principal neurons. Although the relationship between these morphological changes after seizures during development and subsequent cognitive impairment is not yet clear, our findings indicate that during development recurrent seizures can result in significant alterations in cell number and axonal growth. PMID- 9987997 TI - Evidence for a large projection from the zona incerta to the dorsal thalamus. AB - In an effort to understand better how the zona incerta may influence neocortical activity, this study has examined the patterns of projection that this nucleus has to the dorsal thalamus, the "gateway" to the neocortex. To this end, Sprague Dawley rats were anaesthetised with Ketamil (100 mg/kg) and Rompun (10 mg/kg), and injections of biotinylated dextran or cholera toxin subunit B (CTB) were made into various dorsal thalamic nuclei, including the primary relay (dorsal lateral geniculate, medial geniculate, ventral posterior), association (lateral dorsal, lateral posterior, posterior thalamic), and intralaminar (central lateral, parafascicular) nuclear groups, by using stereotaxic coordinates. Brains were aldehyde fixed and processed with standard methods. Our results show that there is a large projection from the zona incerta to the dorsal thalamus. This projection does not blanket all nuclei of the dorsal thalamus but, rather, shows a clear preference for some nuclei over others. After CTB or dextran injections into the primary relay nuclei, very few cells are labelled in the zona incerta. After similar injections are made into the association or intralaminar nuclei, however, many more labelled incertal cells are seen. There are some differences in the distribution of labelled cells within the zona incerta after injections into the association nuclei compared with injections into the intralaminar nuclei. The association nuclei relate strongly to the ventral sector, whereas the intralaminar nuclei relate strongly to the dorsal sector of the zona incerta. After each of these injections into the dorsal thalamus, labelled terminals are seen in the zona incerta also, and their distribution mirrors the distribution of the labelled incertal cells described above. Thus, in summary, our results indicate that the zona incerta has a large and preferential projection to the dorsal thalamus, in particular from the association and intralaminar nuclei. Through this dorsal thalamic projection, the zona incerta is in a position to influence large areas of the neocortex. PMID- 9987998 TI - Cardiac conduction: an interplay between membrane and gap junction. PMID- 9987999 TI - Unipolar stimulation of cardiac tissue. PMID- 9988000 TI - Cellular mechanisms for the slow phase of the Frank-Starling response. AB - Following a step increase in sarcomere length, isometric cardiac muscle tension increases instantaneously by the Frank-Starling mechanism. In isolated papillary muscle and myocytes, there is an additional significant rise in developed tension over the following 15 min due to an unknown mechanism. This slow change in tension could not be explained by mechanical heterogeneity of the muscle preparations or by an increase in myofilament sensitivity to Ca2+. The slow change in tension was not dependent on sarcoplasmic reticulum Ca2+ loading assessed with rapid cooling contractures, and was not significantly altered by sarcoplasmic reticulum Ca2+ depletion (ryanodine) or inhibition of sarcoplasmic reticulum Ca2+ reuptake (cyclopiazonic acid). We used the Luo-Rudy ionic model of the ventricular myocyte together with a model of the length-dependent myofilament activation by Ca2+ to examine the effects of step changes in the parameters of sarcolemmal ion fluxes as possible mechanisms for the slow change in stress. The slow increase in tension was simulated by step changes in the Na+-K+ pump or Na+ leak currents, suggesting that the slow change in stress may be caused by length induced changes in Na+ fluxes. The model also predicted a slow increase in the magnitude of the initial repolarization during phase 1 of the action potential. The combination of experimental and computational models used in this investigation represents a valuable technique in elucidating the cellular mechanisms of fundamental processes in cardiac excitation-contraction coupling. PMID- 9988001 TI - Modeling defibrillation: effects of fiber curvature. AB - The goal of this modeling study is to demonstrate extinguishing of a spiral wave reentry in a sheet of myocardium that incorporates curved fibers. The tissue is represented as a homogeneous bidomain with unequal anisotropy ratios. The spiral wave is initiated via cross-field stimulation of the bidomain sheet. The defibrillation shock is delivered via two line electrodes that occupy opposite tissue boundaries. Simulation results demonstrate that large-scale regions of depolarization are induced under the cathode as well as at locations in the vicinity of the anode. For high shock strengths, the new wavefronts generated from the regions of induced depolarization restrict the spiral wave pathway and render the tissue too refractory to further maintain the reentry. Weak shocks leave large portions of the sheet unaffected allowing the spiral wave to find recovered tissue and thus survive. PMID- 9988002 TI - Focal source hypothesis of atrial fibrillation. PMID- 9988003 TI - Shock timing lowers transvenous defibrillation energy requirement. AB - Previous studies suggested that time periods exist during ventricular fibrillation when defibrillation shocks are more effective. However, there is no agreement on the amount of energy that can be saved or whether an implantable defibrillator can time shocks to these time periods. We conducted a study having two parts to investigate if there was any advantage to synchronizing internal defibrillation shocks to morphological patterns in ventricular fibrillation (VF). VF electrograms were recorded from the same three-electrode lead system used for internal defibrillation. In Part 1, we found no difference in the probability of successful defibrillation between shocks that were delivered into coarse and fine VF (48% vs 46%). However, shocks that were delivered to the upslope of coarse VF electrograms were more efficacious than those to the downslope of the waveform (67% vs 39%, P < .001). In the second study, we developed a real time computer system to prospectively deliver shocks on the upslope feature we identified in the first study. We found that the energy requirements at E50 and E80 were significantly lower for shocks delivered on the upslope of coarse VF than those delivered randomly at the end of 10 sec. We estimated a probability of success (POS) defibrillation curve using a maximum likelihood method for the timed and random shocks. The POS curve width was significantly narrower for shocks that were delivered to the upslope feature than the control treatment (7.1 +/- 0.9 vs. 10.8 +/- 1.7 J, P < 0.01). If these findings extend to clinical defibrillation, they may allow programming of internal defibrillators at lower energies. This could reduce potential postshock cardiac dysfunction, allow production of smaller devices, and improve battery life. PMID- 9988004 TI - Can shocks timed to action potentials in low-gradient regions improve both internal and out-of-hospital defibrillation? AB - During the first minute of fibrillation, circulating wavefronts excite new fibrillation action potentials almost immediately following termination of the preceding action potential. The extension of refractoriness hypothesis states that a successful defibrillating shock must produce a uniform postshock refractoriness of a specific optimal duration throughout the ventricle, which blocks these wavefronts and terminates fibrillation. We hypothesized that, if shocks are appropriately timed early in the fibrillation action potential in low voltage-gradient regions, postshock refractoriness will already be long and the shock need not be strong enough to further extend it. This will result in a lower defibrillation threshold (DFT). This hypothesis was tested in the isolated rabbit heart model. Shocks were synchronized to monophasic action potentials recorded from a low-intensity region. An up/down protocol was used. I50 for early shocks was 17% lower than that for late shocks (31% decrease in E50). Standard deviation of I50 was reduced from 32% for late shocks to 18% for early shocks. Therefore, shock synchronization improves both DFT and intersubject variability during early fibrillation. As fibrillation duration increases, action potential frequency decreases and periods of diastole occur. Because of these ischemic changes, it is uncertain whether shock timing can produce similar improvements in defibrillation under out-of-hospital conditions. PMID- 9988005 TI - Prevention of sudden cardiac death: a current perspective. PMID- 9988006 TI - T-loop morphology as a marker of cardiac events in the elderly. AB - ST-T wave changes of electrocardiographic (ECG) leads have long been recognized as predictors of future cardiac events, but they only imperfectly characterize T loop morphology. Using vectorcardiographic (VCG) parameters, we investigated the predictive value of T-loop abnormality for fatal and nonfatal cardiac events in a prospective cohort study among 5,815 elderly. Separately, the predictive value of an easily obtainable T-loop parameter, the T axis, was also assessed. Measurements were determined by a computer program, using VCGs reconstructed from the standard 12-lead ECGs. During the 3 to 6 (mean 4) years of follow-up, 166 fatal and 193 nonfatal cardiac events occurred. Subjects with an abnormal T-loop morphology had increased risks for fatal cardiac events (hazard ratio 4.3; 95% CI 3.0-6.4) and nonfatal cardiac events (3.0; 1.9-4.8). Risks associated with an abnormal T axis alone were only slightly lower. Additional adjustment for established cardiovascular risk indicators resulted in lower, but still highly significant risks. Both T-loop and T-axis abnormalities appear to be strong, independent risk indicators of cardiac events in the elderly. PMID- 9988007 TI - Integration and communication for the continuity of cardiac care (I4C). AB - The project I4C (Integration and Communication for the Continuity of Cardiac Care) is carried out for the advancement of cardiac care, from prevention to follow-up. The goals of I4C are: (1) integrated access to patient data, wherever they are stored; (2) support of evidence-based care; (3) consistent recording of patient data (eg, patient history, electrocardiograms IECGs] or cine-angios) in a multimedia patient record; and (4) a documented reference data set for research. In several clinics, workstations are being installed to serve the four goals. Integration with other information systems in clinical care is realized by encapsulation. A computer-based patient record (ORCA) has been developed to support the collection, consultation, and sharing of patient data. In I4C, ORCA is intended for use in a research setting as well as routine patient care. The functionality of ORCA covers the collection of patient history data in a highly structured manner, the recording of drug prescriptions, an overview of laboratory test results, and viewers for ECGs and angiographic images. At present, structured data entry and consultation is supported in six European languages. PMID- 9988008 TI - Progress toward a catheter ablative cure of atrial fibrillation. PMID- 9988009 TI - Spectral analysis of the electrocardiogram predicts recurrence of atrial fibrillation after cardioversion. PMID- 9988010 TI - Body surface mapping of atrial arrhythmias: atlas of paced P wave integral maps to localize the focal origin of right atrial tachycardia. AB - Successful curative treatment of right atrial tachycardia (AT) can be obtained provided detailed catheter activation mapping of the target site for radiofrequency energy application has been accomplished. However, right AT mapping may be difficult with a single roving catheter due to infrequent presence or noninducibility of the arrhythmia. The present report describes the preliminary clinical use of body surface mapping as an adjunctive noninvasive method to identify the region of AT origin prior to catheter ablation. This technique has been previously applied to develop a reference data base of 17 different paced P wave integral map patterns. The data base was designed by performing right atrial pace mapping in patients without structural heart disease. Each P wave integral map pattern in the data base is unique to ectopic activation onset in a circumscribed right atrial endocardial segment. Localization of the segment of AT origin is accomplished by matching the P wave integral map of a single AT beat with the data base of paced P wave integral maps. The use of body surface mapping as an integral part of the mapping protocol during radiofrequency catheter ablation of right AT offers the possibility to: (1) noninvasively determine the arrhythmogenic target area for ablation using a single beat analysis approach; (2) confine detailed catheter activation mapping to a limited area; and (3) accelerate the overall procedure and limit fluoroscopic exposure by reducing the time required for mapping. PMID- 9988011 TI - Electroanatomic imaging using magnetic catheter tracking in the diagnosis and treatment of atrial arrhythmias. AB - Recent data emphasize the importance of structural factors in the pathophysiology of atrial arrhythmias. As a consequence, catheter ablation increasingly has become an anatomically oriented procedure. A recently developed magnetic catheter tracking system provides spatially precise and realistic three-dimensional reconstructions of endocardial geometry. A variety of electrophysiologic data can be superimposed on these reconstructions, including activation sequence, electrogram amplitude and morphologic features, response to pacing maneuvers, and sites of planned or delivered radiofrequency energy ablation. These features enhance the ability to analyze and visualize arrhythmia mechanisms, plan and execute appropriate ablation strategies, and provide new opportunities for physiologic research. PMID- 9988012 TI - Use of approximate entropy measurements to classify ventricular tachycardia and fibrillation. AB - Implantable cardiac devices which treat arrhythmias require automated detection to decide when to deliver therapy and, in some devices like the implantable cardioverter-defibrillator (ICD), to determine which therapy to deliver. This type of detection often requires the separation of fibrillatory chaotic rhythms from coherent tachycardias. In the ICD, multiple rate zones can be programmed for detection of ventricular tachycardia (VT) and ventricular fibrillation (VF) and for delivery of therapy: antitachycardia pacing and cardioversion for VT, and defibrillation for VF. Previous research determined that current technology is unable to uniquely classify VF. Analysis of typical settings of the ICD revealed that 40% to 80% of VTs were misclassified as VF (depending on device/setting). Improved detection of VF must be sought in order to capitalize on the cost effectiveness of low-energy VT therapies, potentially saving up to 20% of the life of the battery. In this study, a statistical measure of variability, called approximate entropy (ApEn), has been applied to separate fibrillatory and nonfibrillatory rhythms. Although standard deviation is often used as a measure of variability, it fails to capture the level of regularity or complexity. ApEn improves upon standard deviation by quantifying differences between random and regular signals. ApEn was tested on a small patient set containing VF, VT, and sinus rhythm (SR). Intracardiac recordings (bipolar, ventricular) were selected from the Ann Arbor Electrogram Library (Ann Arbor, MI) where filtering (1-500 Hz), amplification (approximately 1000), and digitization (1000 Hz) are tightly controlled. Results demonstrated that ApEn has the ability to quantify subtle differences between VF and other rhythms. PMID- 9988013 TI - Improved estimation of pericardial potentials from body-surface maps using individualized torso models. AB - Clinical applicability of inferred pericardial potentials is limited because accuracy is significantly affected by noise in surface electrocardiograms (ECGs), errors in electrode location on the torso model, and errors in the geometry and inhomogeneities of the torso model itself. To quantify effects of electrode location and geometric errors in torso-surface models, we measured locations of 190 electrodes used in body-surface mapping of 11 adults, along with over 2,000 sites on each torso surface. Measurements were made to within 2 mm with an Immersion Personal Digitizer. To quantify effects of errors in pericardial surface models we also estimated heart position, size, and orientation in each subject from ultrasonic images registered to the body-surface coordinates. Known pericardial potentials were taken from epicardial measurements made during QRS with a 90-electrode sock in an adult male undergoing cardiac surgery. Body surface ECGs were calculated for each individual from the pericardial maps, using standard boundary-element methods. Accuracy of zero-order-Tikhonov inverse solutions was tested in 91-node pericardial and 1,026-node torso models, individualized for each subject. With 10 microv rms noise added to surface potentials, the optimal regularization constant at each instant in QRS gave a relative error of 0.44 +/- 0.03; it was 0.47 +/- 0.03 using the composite residual and smoothing operator (CRESO) technique. When calculated body-surface potentials from the first 10 subjects were placed at corresponding electrode positions on the torso of the eleventh subject, whose heart size and orientation was the mean of the other 10 subjects, relative error increased to 0.87 +/- 0.06 for optimal regularization. CRESO failed in the fixed torso model. Results demonstrate that a fixed model does not provide useful estimates of pericardial potentials, and that individualized models enhance the performance of techniques for the estimation of regularization parameters. PMID- 9988014 TI - ECG features of microvolt T-wave alternans in coronary artery disease and long QT syndrome patients. AB - T-wave alternans (TWA) is a marker of myocardial electrical instability. We compared ECG features of microvolt TWA in coronary artery disease (CAD) and long QT syndrome (LQTS) patients. METHOD: The study populations consisted of 43 CAD and 39 LQTS patients. TWA was detected in resting Holter recordings using the new correlation method (CM). After preprocessing to adjust for RR variability and respiratory modulation, CM was used to quantify TWA amplitude (A(CM)), duration (N(CM)), and magnitude (MAG(CM); defined as the product of A(CM) and N(CM)). RESULTS: TWA was detected in 19 (44%) CAD and 17 (44%) LQTS patients. TWA was associated with longer RR intervals (P = 0.006) and had larger magnitudes (P = 0.067) in LQTS than CAD patients. The TWA was identified as transient (nonstationary) in 15 of 19 (79%) TWA-positive CAD patients, and in 8 of 17 (47%) TWA-positive LQTS patients (P = 0.047). CONCLUSIONS: The frequency of TWA detected with CM is similar in LQTS and CAD patients. TWA is larger in LQTS than in CAD patients, whereas TWA is more frequently transient (nonstationary) in LAD than LQTS patients. In LQTS patients, but not in CAD patients, a longer RR is associated with TWA, indicating different electrophysiologic mechanisms in the two pathologies. PMID- 9988015 TI - Prediction of normal QT intervals in children. AB - Measuring QT intervals in individual children is of great importance, particularly in view of increasing evidence linking long QT syndrome to subsequent risk for sudden death. Three hundred seventy-three healthy subjects, 185 women and 188 men, aged 5.2 to 16.5 years, were investigated with a 12-lead standard electrocardiogram (ECG). Values for predicted QTp50 and QTp95 (percentiles) were calculated by using the cycle length (RR interval [RRI]) and the measured QT interval. We used multiple regression analysis to test the influence of possible important variables and the resulting data were used to generate tables. Additionally, predicted QTp values were compared to QTc values after Bazett's correction. RRI, body height, age, and sex turned out to influence the QTp values most. For clinical use, data are presented in tabular form by RRI and age for both genders. The tables are of great clinical value in predicting the upper limits of normal QTp95 for individual children. Bazett's correction tends to underestimate the values found in our data when heart rate increases. PMID- 9988016 TI - Differences between local investigator and core-laboratory interpretation of the admission electrocardiogram in patients with unstable angina pectoris or non-Q myocardial infarction (a thrombin inhibition in myocardial ischemia [TRIM] substudy). PMID- 9988017 TI - Determinants of precordial QT dispersion in normal subjects. AB - Dispersion of precordial QT intervals has been attributed to delay in the recovery process in the myocardium under the exploring electrode, a local effect. However, the phenomenon also could be explained by different projections of the heart vector, in which case the 12-lead electrocardiogram (ECG) derived from the heart vector would show similar dispersion that could not be local in nature because the electrical activity of the heart is represented by a single dipole. Using an analog device that switched between the two, conventional and derived ECGs were obtained from 129 normal subjects. Measured as the difference between the longest and shortest precordial QT intervals, QT dispersion from the derived ECGs (mean +/- SD, 40 +/- 20 ms) was nearly identical in magnitude to that from the standard ECGs (41 +/- 18 ms, P = NS). Further analysis of the derived ECGs revealed nonuniform distributions of both the maximal and minimal QT intervals across the precordial leads. In addition, a weak correlation was found between the QT interval and the T wave amplitude in the two precordial leads with the lowest T-wave amplitudes (r = -0.303 in V1, P = .001, and r = 0.253 in V6, P = .005). While findings in patients with disease or with abnormal ECGs may differ and require separate examination, these data suggest that the observed magnitude of precordial QT dispersion in normal subjects can be explained by differences in precordial projection of the end of the T wave rather than by local effect. PMID- 9988018 TI - Beat-to-beat repolarization variability in amplitude and duration in LQTS patients with the SCN5A sodium channel gene mutation. PMID- 9988019 TI - A comparison of simulated QRS isointegral maps resulting from pacing at adjacent sites: implications for the spatial resolution of pace mapping using body surface potentials. AB - The precise localization of ventricular tachycardia (VT) foci is a prerequisite for the successful radiofrequency catheter ablation in patients. The purpose of this study was to systematically quantify over what distance adjacent sites in the right ventricular (RV) and left ventricular (LV) epicardium and LV endocardium could be distinguished by inspecting morphological features of QRS isointegral maps using statistical methods. We investigated the spatial resolution of QRS isointegral maps by means of an anatomically accurate computer model of the human ventricular myocardium that incorporates a bidomain model for simulating the realistic activation sequences and the oblique dipole model in combination with the boundary element method for calculating extracardiac potentials. In this model, we initiated activation sequences at a total of 183 epicardial and 75 LV endocardial pacing sites, positioned in three levels (basal, middle, and apical). For each of the 258 pacing sites, we calculated a set of 10 QRS isointegral maps with added Gaussian noise at 117 leads (covering the anterior and posterior torso) and at 32 leads (covering only the anterior torso), respectively. Sets of maps were then cross correlated and root-mean-square (RMS) values of difference maps were calculated for all possible pairs of pacing sites on the same level. We applied the nonparametric unpaired Kolmogorov-Smirnov test and defined the spatial resolution as the pacing site separation at which the differences in correlation coefficients and RMS differences were significant (level P < .05). We observed significant differences in maps when the distances between pacing sites were on average (+/- SD) greater than 4.3 +/- 1.0 mm. In more than 90% of pacing sites, the significant differences in maps were observed within 4 mm even when using a 32-lead mapping system. The findings of our study provide theoretical evidence that QRS isointegral maps may offer noninvasive means for preinterventional planning of the ablative treatment in localizing both endocardial and epicardial sites of origin of VT. PMID- 9988020 TI - A simulation study of Torsade de Pointes with M cells. AB - Recent studies have reported the relation between Torsade de Pointes (TdP) and midmyocardial (M) cell function associated with long QT syndrome. To investigate this relation, we conducted a simulation study with a three-dimensional (3D) heart model incorporating M cells in the anterolateral areas of the model. Parameters of premature cycle-length dependent shortening of action potential duration (APD) and conduction velocity for the M cells were adjusted to induce tachyarrhythmias of TdP type. Under a basic pacing cycle length of 1,000 msec at the sinus node, four successive premature beats of 160-ms interval were generated 300 ms after the first sinus pacing. Setting lower conduction velocity and longer APD to M cells induced sustained TdP-like tachyarrhythmia resembling ECG findings. TdP could not be induced without the presence of M cells. This study suggests that TdP might be caused by reentry around M cells and dispersive refractory areas due to prolonged APD and slow conduction velocity. PMID- 9988021 TI - Ventriculoatrial conduction metrics for classification of ventricular tachycardia with 1:1 retrograde conduction in dual-chamber sensing implantable cardioverter defibrillators. AB - The introduction of dual-chamber sensing in implantable cardioverter defibrillators (ICDs) has greatly reduced the incidence of false detection due to supraventricular tachycardias. The remaining arrhythmias which serve to confound classification are supraventricular tachycardias (SVTs) with 1:1 anterograde conduction and ventricular tachycardias (VT) with 1:1 retrograde conduction. An algorithm has been designed and tested (28 patients) which employs ventriculoatrial (VA) conduction measurements to separate 1:1 VTs from 1:1 SVTs. A study was conducted to assess realistic VA interval boundaries for classification of arrhythmias with 1:1 retrograde atrial conduction. Intracardiac atrial and ventricular recordings of 7 passages of VT with retrograde conduction, 12 passages of atrioventricular nodal reentrant tachycardia (AVNRT), 3 passages of atrial tachycardia (AT), 8 passages of sinus tachycardia (ST), and 2 passages of orthodromic reentrant tachycardia (ORT) were analyzed. Automated real-time atrial and ventricular waveform recognition was performed on each passage and VA intervals were measured. Separation of VT with retrograde conduction from other 1:1 supraventricular tachycardias was effected by imposing discrete VA interval boundaries. VA boundaries of 80 ms to 234 ms classified 1:1 VT with 100% sensitivity (SENS) and 80% specificity (SPEC). In addition, the lower boundary completely classified AVNRT with 100% SENS and 100% SPEC, and all passages of ST were contained above the upper boundary. These findings could be of importance in algorithms for next-generation implantable cardioverter defibrillators which include two-chamber (atrial and ventricular) sensing and two-chamber interval measurements. PMID- 9988022 TI - Identification of best electrocardiographic leads for diagnosing acute myocardial ischemia. PMID- 9988023 TI - ST segment elevation and the prediction of hospital life-threatening complications: the role of right ventricular and posterior leads. AB - Accurate prognosis in suspected acute myocardial infarction (AMI) is essential for appropriate use of thrombolytic therapy and primary angioplasty. However, previous models may be limited because the 12-lead electrocardiogram (ECG) does not examine the right ventricular (RV) and posterior myocardium. We evaluated ST segment elevation (STSE) in posterior (V7-V9) and RV (V4R-V6R) leads to determine their predictive value for hospital life-threatening complications (HLTCs). METHOD AND RESULTS: This prospective trial of seven Midwestern hospital emergency departments (EDs) had inclusion criteria of age 35 years, chest pain suggestive of ischemia, and coronary care unit (CCU) admission. ECG leads were test positive if STSE was > 0.1 mV. Patients were positive for HLTCs if ED or inpatient hospital course included: ventricular fibrillation or tachycardia, second- or third-degree block, shock, arrest, or death. Univariate and multivariate analyses were performed to test each lead's association with HLTCs. Of 533 patients, 64.7% (345/533) had AMI and 15.8% (85/533) had HLTCs. The sensitivity of 18 leads for HLTCS was increased by 5.8%, but specificity decreased by 8.2%. ECG subgroups by STSE were associated with the following HLTC rates: inferior/+RV (32.4%); anterior (29.5%), lateral (23.1%), inferior RV (17.9%), and posterior (16.2%). V1 (odds = 3.2) and V6R (odds = 3.1) were statistically significant independent predictors. CONCLUSION: Posterior and RV leads did not increase the ECG's overall prognostic value, but in the presence of inferior STSE, were associated with low and high complication rates, respectively. Right and left precordial leads were the best predictors of HTLCs. PMID- 9988024 TI - Routine use of a 15-lead electrocardiogram for patients presenting to the emergency department with chest pain. PMID- 9988025 TI - Normal limits of ST segment measurements in posterior ECG leads. PMID- 9988026 TI - Body-surface map models for early diagnosis of acute myocardial infarction. AB - The standard 12-lead ECG is only 50% sensitive for the detection of acute myocardial infarction (AMI). The majority of leads for optimal classification of AMI probably lie outside the area covered by the 6 precordial leads. Thus, body surface mapping (BSM) may be more helpful, as a larger thoracic area is sampled. We recorded 64-lead anterior BSMs in 635 patients with chest pain suggestive of AMI and abnormal electrocardiograms (ECGs), and 125 controls without chest pain. Of the 635 patients, 325 had AMI according to World Health Organization (WHO) criteria (203 presenting with ST segment elevation, and 122 with nondiagnostic ECG), and 310 had an "abnormal ECG but not AMI." QRS and ST-T isointegrals and variables describing map shape were derived. Subjects were randomly allocated to a training set (63 controls, 321 patients) and a validation set (62 controls, 314 patients). Multiple logistic regression was used in the training set to identify which variables gave best discrimination between groups. A model with these variables was then tested prospectively in the validation set. In stage 1 (all subjects), controls were compared with patients. In the training set, a model containing 21 variables classified 58/63 controls (specificity 92%) and 316/321 patients (sensitivity 98%). In the validation set, the model classified 48/62 controls (specificity 77.4%) and 302/314 patients (sensitivity 96%). In stage 2 (studying patients only), patients with AMI were compared with patients who had an abnormal ECG-not AMI. In the training set, a model containing 28 variables classified 132/165 patients (sensitivity 80%) with AMI and 134/156 patients (specificity 86%) with an abnormal ECG-not AMI. In the validation set, the model classified 123/160 patients (sensitivity 77%) with AMI and 131/154 patients (specificity 85%) with an abnormal ECG-not AMI. Combining results of both stages in a two-step algorithm gave an overall classification in the training set of controls 92%, abnormal ECG-not AMI 84%, AMI 80%, and in the validation set of controls 77%, abnormal ECG-not AMI 82%, AMI 74%. Thus, in conclusion, when compared with the 12-lead ECG, BSM models results in higher sensitivity and specificity for detection of AMI, particularly in patients presenting with chest pain and nondiagnostic ECG changes. The use of BSM models in such patients, may lead to the earlier detection of AMI and appropriate administration of fibrinolytic therapy and/or anti-platelet agents. PMID- 9988027 TI - Task complexity effect on vocal reaction time in aged speakers. AB - The aged population is at risk for impaired speech communication due to the increased likelihood of deterioration of central nervous system (CNS) processes that underlie cognition, language, and/or speech motor control. Vocal reaction time (RT) may provide a means of quantifying the efficiency of CNS processes that underlie speech production. The present study used a simple RT paradigm to investigate effects of the complexity of the required task on vocal RT in normal young and aged speakers. Task complexity was represented by two levels: a single word and a short sentence. Only the aged subjects showed a significant task complexity effect on vocal RT. Furthermore, the between-group RT difference increased as a function of task complexity. Specific causes for the increase in vocal RT for the aged subjects are presently unknown, but likely reside in altered respiratory biomechanics and reduced efficiency of CNS motor processing. PMID- 9988028 TI - Correspondence of electroglottographic closed quotient to vocal fold impact stress in excised canine larynges. AB - The purpose of this study was to explore the possible use of the electroglottographic closed quotient (EGG CQ) as a noninvasive estimate of vocal fold impact stress (SI). Two excised canine larynges were used. Each larynx was mounted and vocal fold oscillation was induced using a humidified air source. Twenty-seven experimental trials were conducted for each larynx. Trials involved variations in vocal process gap, vocal fold elongation, and subglottic pressure. Simultaneous measures were made of vocal fold SI at the midpoint of the membranous vocal folds, and EGG CQ (dimensionless ratio). The results indicated that when threshold and saturation effects were excluded, the SI and the CQ were strongly related (linear correlation r = .83 and .96 for the two individual larynges, and .81 for the combined data). Within the region of linear relation, an increase of.15 in the CQ corresponded to about 1 kPa increase in SI for the combined data. Discussion focuses on possible clinical implications and the likely reasons for threshold and saturation phenomena. PMID- 9988029 TI - Effects of lung volume on the glottal voice source. AB - According to experience in voice therapy and singing pedagogy, breathing habits can be used to modify phonation, although this relationship has never been experimentally demonstrated. In the present investigation we examine if lung volume affects phonation. Twenty-four untrained subjects phonated at different pitches and degrees of vocal loudness at different lung volumes. Mean subglottal pressure was measured and voice source characteristics were analyzed by inverse filtering. The main results were that with decreasing lung volume, the closed quotient increased, while subglottal pressure, peak-to-peak flow amplitude, and glottal leakage tended to decrease. In addition, some estimates of the amount of the glottal adduction force component were examined. Possible explanations of the findings are discussed. PMID- 9988030 TI - An acoustical and perceptual analysis of the vocal behavior of classroom teachers. AB - This study examined perceptual evaluations of classroom teachers, acoustic measures of their voices ( fundamental frequency [F0], frequency range [F0SD], % jitter, and % shimmer), and behavioral measures (rate, dysfluencies, and episodes of vocal fry). This preliminary study attempted to identify perceptual and acoustic measures that discriminate between effective and less effective classroom teachers. Seven teachers were recorded on audiotape while presenting a 10-12 minute lecture. Voice samples (N > 200) for each teacher were subjected to acoustic analysis. Audiotapes were evaluated by listeners (N = 180), who scale rated and used an adjective checklist to determine teachers' overall effectiveness. A three-member team evaluated global aspects of voice (e.g., use of pauses, inflections, contours, and phrasing). Results indicated that frequency range, frequency variability, rate, and number of dysfluencies appeared to correlate with perceptual judgments of teaching effectiveness and specific adjective descriptors. F0, % jitter, and % shimmer did not appear to be linked to perceptual judgments. Individual case profiles were established and recommendations were made for future empirical research involving larger samples of teachers. PMID- 9988031 TI - Acoustic voice analysis in patients with essential tremor. AB - To quantify several acoustic features of the voice in patients with essential tremor (ET), 28 patients and 28 age- and sex-matched controls were studied. ET severity was assessed with the rating scale for tremor of Fahn, Tolosa, and Marin. The Computerized Speech Lab 4300 program (Kay Elemetrics) was used. Two second samples of a sustained /a/ and a sentence were captured with a microphone and laryngograph equipment. Measures included fundamental frequency (F0), frequency perturbation (jitter, Koike algorithm), intensity perturbation (shimmer, Horii algorithm), and harmonic-to-noise ratio (H/N, Yumoto algorithm) of the vowel /a/, and the frequency and intensity variability of the sentence, phonational range, and dynamic range at the natural frequency, maximum phonational time, and s/z ratio. All subjects underwent indirect laryngoscopy and/or laryngeal fibroscopy. When compared with controls, ET patients showed higher jitter, lower H/N ratio (the last one only with laryngographic signal), of the vowel /a/, lower frequency variability in the microphonic signal, lower intensity variability in the laryngographic signal of the sentence, and significantly lower dynamic range at natural frequency of phonation. ET patients reported higher frequency of the presence of high voice intensity, tremor, and struggle. Several acoustic parameters were influenced by the severity of the disease, including shimmer, jitter, H/N ratio, frequency variability of the sentence, and s/z ratio, although neither of the acoustic analysis values or the phonetometric measurements were affected by the presence of voice tremor or by a successful pharmacological treatment of ET. PMID- 9988032 TI - Reliability of single sample experimental designs: comfortable effort level. AB - This study was designed to ascertain the intrasubject variability across multiple recording sessions-most often disregarded in reporting group mean data or unavailable because of single sample experimental designs. Intrasubject variability was assessed within and across several experimental sessions from measures of speaking fundamental frequency, vocal intensity, and reading rate. Three age groups of men and women--young, middle-aged, and elderly--repeated the vowel /a/, read a standard passage, and spoke extemporaneously during each experimental session. Statistical analyses were performed to assess each speaker's variability from his or her own mean, and that which consistently varied for any one speaking sample type, both within or across days. Results indicated that intrasubject variability was minimal, with approximately 4% of the data exhibiting significant variation across experimental sessions. PMID- 9988033 TI - The effect of patient factors on response outcomes to Botox treatment of spasmodic dysphonia. AB - Injection of botulinum toxin (Botox) into the laryngeal muscles has become the treatment of choice for controlling the symptoms of spasmodic dysphonia (SD). Currently, no specific battery of objective tests to assess the outcome is universally accepted. The purpose of this study was to investigate demographic, clinical, and treatment factors with voice outcome following Botox injection. Sixty-eight patients with adductor SD who underwent at least one Botox injection during a 5-year period were studied. Voice outcome measures were made from patient self-reporting scales and included overall vocal quality, length of response, and duration of breathiness. Vocal quality was significantly correlated with the underlying severity of vocal symptoms prior to treatment, incidence of breathiness and unilateral versus bilateral injection. The length of response was greater in males and following bilateral injections. An increased period of breathiness significantly correlated with bilateral injections. PMID- 9988034 TI - Prevalence of voice problems in teachers. AB - Teachers are frequently cited as experiencing a high rate of vocal dysfunction (1 7). Despite considerable research in the area of voice problems in teachers, the prevalence of voice disorders in this group is unknown. This study investigated the prevalence of self-reported voice problems in teachers using a mail survey of a simple random sample of 1168 state school teachers (preschool-Grade 12) in South Australia. As part of the survey, teachers were asked to report voice problems for the day of the survey, during the current teaching year, and during their careers. The response rate was 75%, with 16% of teachers reporting voice problems on the day of the survey, 20% reporting problems during the current teaching year, and 19% reporting problems at some time during their career. Females were twice as likely as males to report voice problems. These findings clearly indicate a need for further investigation of the causes of vocal dysfunction in teachers and for the development of educational programs aimed at preventing voice problems in this group of professional voice users. PMID- 9988035 TI - Frequency of voice problems among teachers and other occupations. AB - This study describes the frequency of reporting vocal problems among a random sample of elementary and high school teachers (n = 554) compared to individuals working in other occupations (n = 220). Teachers were more likely to define themselves as ever having a voice problem (32% versus. 1%, p < .05); having a tired, weak, or effortful voice (p < .05 each); and having a higher frequency of symptoms of physical discomfort with speaking (p < .05). They also were more likely to perceive that their voice problem negatively affected current job performance (p < .05) and limited options regarding change in work (p < .05). About 20% of teachers but only 4% of nonteachers had missed work due to their voice. These findings suggest that teachers are at high-risk for disability from voice disorders and that this health problem may have significant work-related and economic effects. PMID- 9988036 TI - Vocal problems among teachers: a review of prevalence, causes, prevention, and treatment. AB - Voice disorders are thought to be one of the major occupational hazards of school teaching. The resulting symptoms can affect teachers' ability to function in the classroom and prevent them from developing effective working relationships with other staff and students. Sick leave, speech pathology management, and surgical intervention can be costly. Severe voice problems can also result in a teacher permanently leaving the classroom. Despite the significant implications of voice disorders for teachers, this review of published research demonstrates that findings concerning the prevalence of voice problems in teachers and the causes and contributing factors of those voice problems are inconclusive. Similarly, previous research on the efficacy of prevention programs and treatment of voice problems in teachers provide few firm conclusions. Further research based on sound empirical data is needed, as many past studies have relied on anecdotal or self-report data. More operational definitions of what constitutes a voice disorder and the associated contributing factors should be adopted, along with the use of more instrumental measures and careful attention to methodology and appropriate statistical analyses. Only then will we have a sound basis for the development of effective prevention and education programs for teachers. PMID- 9988037 TI - Learning voice analysis using an interactive multi-media package: development and preliminary evaluation. AB - An important outcome of education for speech-language pathology practice is the ability to analyze voices perceptually, a complex task that is often difficult for novices. This article describes an interactive multi-media package, "A Sound Judgement," that is designed to help students develop skills in perceptual voice analysis and to link their perceptions to laryngeal physiology. The package presents a range of clients with vocal impairments at increasing levels of complexity. Each case has a videoed interview, endoscopic views and animations of the larynx, and case history information. Students make perceptual ratings of clients' voices on a format designed specifically for this package and feedback is provided using ratings made by expert speech-language pathologists. High levels of consensus for the perceptual judgments were achieved among the expert raters. Preliminary evaluations by students have demonstrated that "A Sound Judgement" is likely to be a valuable educational tool. PMID- 9988038 TI - A multi-media, computer-based method for stroboscopy rating training. AB - Methods of training individuals to rate stroboscopic examinations vary widely in rating criteria, viewing times, samples, and length of training. Consequently, problems occur in both inter- and intrajudge agreement. Computer-aided instruction (CAI) provides a means to integrate and control key learning factors that facilitate learning. This study attempted to determine if CAI could train individuals to make accurate and reliable visuo-perceptual judgments of stroboscopy. Experienced and inexperienced subjects rated 45 samples before and after training. Following 4 to 5 hours of CAI training, the subjects with no previous experience demonstrated improved interjudge agreement with a panel of expert raters. The training was not effective for the experienced group. Regardless of the rater's experience, the parameters that required evaluation of movement were more difficult to rate than those requiring only an assessment of structure. PMID- 9988039 TI - Psychogenic dysphonia: peeling back the layers. AB - Resolution of psychogenic dysphonia is often quick and effortless for client and therapist alike. In such instances, the therapeutic interventions are simple and straightforward, insights are reached without difficulty, and once normal voice has been established, resumption of dysphonia or other psychosomatic symptoms rarely occurs. Sometimes, however, psychogenic dysphonia is extremely difficult to overcome, requiring considerable time, effort, and determination on the part of the client, coupled with confident, skilled persistence and psychotherapeutic insight from the therapist. In such cases one feels a sense of working through many complex layers before obtaining satisfactory voice or reaching an understanding of the psychogenic factors that precipitated onset and/or maintenance of the dysphonia. Two cases that illustrate this involved process of peeling back the layers are presented. For resolution of severe psychogenic dysphonia, the therapist must be able to recognize and establish the complex relationship between the neurophysiological, intrapsychic, and interpersonal levels of function as they affect the client's voice and person, as a whole. This work requires considerable courage and skill on the part of the therapist to question, explore, change direction, and select alternative approaches. It is important that the problem can be resolved with a depth of understanding which is relevant for the client, and with due attention to the social context and wider systems of which he or she is a part. PMID- 9988040 TI - Outpatient transoral laser vaporization of anterior glottic webs and keel placement: risks of airway compromise. AB - Management of acquired anterior glottic webs involves resection of the web with reconstitution of a linear vocal fold edge and anterior commissure. Traditional procedures such as transcervical midline thyrotomy (with tracheostomy) and keel placement have been used for patients with extensive scar formation and airway compromise. However, in selected patients with more limited scarring and minimal to-no airway compromise, a transoral endoscopic approach may be a viable option. In three patients, transoral laser vaporization followed by transoral keel placement and outpatient removal resulted in a vocal quality that perceptually improved without any evidence of respiratory compromise postoperatively. PMID- 9988041 TI - Assessing outcomes for dysphonic patients. AB - This study was designed to evaluate a disease-specific outcome measure for patients with selected voice disorders and to relate this instrument to a standardized quality of life measurement. In addition, the study attempts to document the degree of handicap for dysphonia patients globally, between different vocal pathologies, and in comparison to other chronic diseases. In this prospective, observational study, 260 adult patients evaluated for alterations of voice completed a general quality of life measure (the Medical Outcomes Trust Short Form 36-Item[SF-36]) and a voice-specific instrument (Voice Handicap Index [VHI]) pretreatment. The highest correlation was between the social functioning score of the SF-36 and the total score of the VHI and the physical, emotional, and functional subscales (p < 0.001) of the VHI. Significant correlation was also obtained for the SF-36 domains mental health (p < 0.01), general health (p < 0.01), and role functioning emotional (p < 0.017) with the three VHI domains and the total VHI score. Patients had significantly lower scores than the general U.S. population in five of the eight domains of SF-36. Patients with vocal fold paralysis had the highest level of pretreatment disability as measured on both the VHI and SF-36 among voice patients. The patients with dysphonia had a lower level of physical functioning than the patients with chronic sinusitis (p < 0.01), reflecting a greater handicap. In addition, the dysphonia group had lower levels of social functioning than the angina (p < 0.01) and sciatica (p < 0.01) groups and a lower score for mental health than the angina group (p < 0.01). The SF-36 correlates with the VHI in the domains of social functioning, mental health, and role functioning emotional. The baseline handicap for voice disorders represents a significant disability even in comparison to conditions such as angina pectoris, sciatica, and chronic sinusitis. PMID- 9988042 TI - Functional impact of nodules: a case-comparison study. AB - Patients diagnosed with nodules (NO = 40) in a large university hospital clinic and an age-stratum matched nondiseased group (ND = 200) described adverse outcomes of vocal impairment on work and work-related communications. NOs were significantly more likely than NDs to report symptoms of hoarseness (73% vs. 26%), high-note difficulty (70% vs. 20%), difficulty speaking with a lower voice (53% vs. 13%) and a tired voice (50% vs. 10%), and their greatest source of physical discomfort was associated with scratchiness (61% vs. 3%). The average number of symptoms was four in NOs and less than one in NDs. Nodule patients were most concerned about the effects their voice problem would have on their future career (78% vs. 24%) and 49% of NOS reported their voice problem had an adverse work effect in the past compared with 4% of NDs. Having a voice condition limited current job performance in 39% of the NO group but only in 2% of the ND group. The results suggest that a diagnosis of nodules plays a major role in disrupting careers and work activities and that available educational programs and additional research are needed for improving their functional ability and preventing adverse outcomes in the lives of individuals with voice disorders. PMID- 9988043 TI - Mechanisms of quinolone resistance in clinical strains of Pseudomonas aeruginosa. AB - Principal mechanisms of bacterial resistance to quinolones are modification of target enzymes, DNA gyrase (gyrA) and topoisomerase IV (parC), or reduction of intracellular concentration due to mutations in the regulatory genes for efflux systems, such as mexR and nfxB. We have examined gyrA, parC, mexR, and nfxB genes from 16 quinolone-resistant clinical isolates of Pseudomonas aeruginosa to determine the relation between mutations in DNA replicating enzymes or regulatory genes for efflux systems and to correlate the mutations with minimal inhibitory concentrations (MICs). The quinolone resistance-determining regions (QRDR) of these genes were amplified by PCR and sequenced by capillary electrophoresis. Fourteen of 16 isolates had mutations in gyrA, and 13/14 strains with MIC to norfloxacin > or = 8 mg/L had threonine at position 83 changed to isoleucine. Seven of 8 strains with MIC > or = 32 mg/L had mutations in parC. One of these strains showed a parC mutation at position 74 without any mutation in gyrA. Four strains had mexR and two strains nfxB mutations. The data indicate that gyrA mutation is the most important component of quinolone resistance, and simultaneous presence of parC mutations is associated with high-level resistance. parC mutation alone may contribute to resistance, and gyrA mutation may not be a prerequisite for parC mutation to express resistance. mexR and nfxB mutations were found mostly in strains with high-level resistance. PMID- 9988044 TI - Comparison of PCR-heteroduplex characterization by automated DNA sequencing and line probe assay for the detection of rifampicin resistance in Mycobacterium tuberculosis isolates from KwaZulu-Natal, South Africa. AB - Progress in understanding the basis of resistance to rifampicin (RifR) has allowed molecular tests for the detection of drug-resistant tuberculosis to be developed. One hundred thirteen strains of Mycobacterium tuberculosis isolated from patients with multidrug resistant tuberculosis (MDR-TB) were investigated for genotypic analysis of RifR by polymerase chain reaction-heteroduplex formation (PCR-HDF) and characterization of mutations by automated DNA sequencing of the rpoB gene. A subset of isolates (22) representative of different mutations as confirmed by sequence analysis were also evaluated by the Line Probe Assay (LiPA). In 106 of the RifR strains, 24 mutations within an 81-bp region of the rpoB gene affecting 13 amino acids were observed. Most isolates (7/8) harboring Leu533 --> Pro codon mutation required minimum inhibitory concentrations (MICs) of < or = 8 microg/ml. There was geographic variation in the frequency of occurrence of particular rpoB mutations, with the Ser531 --> Leu/Trp codon mutation found in 59/113 of isolates. Although there are certain limitations in the use of both the rapid PCR-HDF diagnostic assay and the LiPA for the detection of rifampicin susceptibility of M. tuberculosis, these provide important and convenient tools for identifying and managing patients with MDR-TB. PMID- 9988045 TI - Analysis of the mutations involved in fluoroquinolone resistance of in vivo and in vitro mutants of Escherichia coli. AB - We searched for the mutations involved in high-level fluoroquinolone resistance (ciprofloxacin MIC > or = 8 microg/ml) of 11 clinical isolates of Escherichia coli. trans-Complementation tests with the wild-type gyrA and parC genes were positive for all strains whereas negative results were observed with the wild type gyrB and parE genes. By PCR and sequencing, two mutations in gyrA, leading to Ser-83 --> Leu and Asp-87 --> Asn (7) or Gly (2) or Tyr (1) changes, were found in 10 strains, the eleventh presenting only the Ser-83 --> Leu change. In addition, all strains carried one change in ParC: Ser-80 --> Ile (8) or Arg (2); Glu-84 --> Lys (1). We described a novel and simple method permitting detection of the mutations in parC at codon 80, PCR-RFLP with HaeII. In vitro mutants, selected with ciprofloxacin in three successive steps were also studied. The first-step mutants were complemented by pJSW101 (gyrA+) but not by pEN260 (parC+), whereas the second-step and third-step mutants were complemented by both plasmids. Mutations occurred in the following order: (i) gyrA at codon 83 (Ser to Leu change), (ii) parC at codon 80 (Ser to Ile change), and (iii) gyrA at codon 87 (Asp to Asn change). Thus, these sequential mutations appear to be frequently involved in high-level fluoroquinolone resistance of E. coli. PMID- 9988046 TI - Spread of a methicillin-resistant and multiresistant epidemic clone of Staphylococcus aureus in Argentina. AB - One hundred forty-eight recent methicillin-resistant Staphylococcus aureus (MRSA) isolates collected from 13 hospitals in Argentina were examined for antibiotic susceptibility and clonal type, using hybridization with DNA probes specific for mecA and Tn554, and pulsed-field gel electrophoresis (PFGE) of chromosomal SmaI digests. The majority of the isolates (62.2%) shared the common PFGE B pattern and carried variants of mecA and Tn554 polymorphs characteristic of an MRSA clone widely spread in Brazilian hospitals. Similarly to the Brazilian isolates, the MRSA clone recovered in the Argentinian hospitals (XI::B::B) and its close relatives (XI::B'::B, XI::AA::B, XI::M::B, XI::omega omega::B, and III::W::B) showed susceptibility to spectinomycin and resistance to numerous antibacterial agents, including beta-lactams, tetracycline, aminoglycosides, macrolides, trimethoprim/sulfamethoxazole, ciprofloxacin, and fosfomycin, and more than 60% of the isolates were also resistant to chloramphenicol and rifampin. The XI::B::B MRSA clone represented the majority of isolates recovered in most of the hospitals, nine of which were located in the city of Buenos Aires, three in the province of Buenos Aires, and one in the province of Tucuman, 1,312 km northwest of the city of Buenos Aires. The observations document further geographic expansion of this South American MRSA clone across national boundaries. PMID- 9988047 TI - Antibiotic resistance in Escherichia coli of the normal intestinal flora of swine. AB - Twelve hundred enterobacterial Escherichia coli isolates of porcine origin were screened phenotypically for antibiotic resistance. The bacteria were isolated from 10 herds of swine with different histories of exposure to antimicrobial agents for therapeutic purposes. The bacterial isolates were part of the normal bacterial flora of the intestines of the animals because they were isolated from healthy individuals. The strains were tested for phenotypic antibiotic resistance against sulfonamides, trimethoprim, streptomycin, ampicillin, neomycin, chloramphenicol, and tetracycline. Resistance against streptomycin was found to be most common, followed by resistance against sulfonamides and tetracycline. The highest number of resistant bacteria was found in herds where the use of antimicrobial agents was considered to be high. A selection of multiresistant bacterial isolates were further genetically characterized by hybridization with probes specific for the antibiotic resistance genes; sulI, sulII, dfrI, dfrIIb, dfrIX, and the class A, B, C, and D tetracycline resistance determinants. A PCR was developed and used for detection of the strA-strB gene pair encoding streptomycin resistance in gram-negative bacteria. The strA-strB gene pair was the most frequent resistance determinant in the isolates examined. This study indicates that nonpathogenic E. coli from swine may represent a considerable reservoir of antibiotic resistance genes that might be transferable to pathogens. PMID- 9988048 TI - Susceptibility and genetic relatedness of invasive Haemophilus influenzae type b in Italy. AB - Haemophilus influenzae type b (Hib) still causes a large portion of meningitis in children less than 5 year old in Italy because vaccination against this agent has not been fully implemented in the country. We have studied 78 Hib strains and 4 nontypable H. influenzae (NTHi) isolated from the cerebrospinal fluid of subjects with meningitis for susceptibility to ampicillin, chloramphenicol, and ceftriaxone. The macrorestriction profiles of chromosomal DNA obtained by pulsed field gel electrophoresis (PFGE) following digestion with SmaI and ApaI were also determined. All strains except one were equally susceptible to the antibiotics tested. One Hib strain, the only beta-lactamase producer, showed an intermediate susceptibility to ampicillin (MIC = 2 microg/ml), while maintaining full susceptibility to chloramphenicol and ceftriaxone. The analysis of the PFGE patterns showed that most of the Hib isolates, including the beta-lactamase positive Hib strain, belonged to the same clone or to closely related subclones. For three PCR-confirmed NTHi isolates, we obtained completely different PFGE profiles. In conclusion, resistance to ampicillin still appears to be a rare finding in Hib strains causing meningitis in Italy; moreover, PFGE showed that the population structure of invasive Hib is essentially clonal. PMID- 9988049 TI - Effect of tylosin used as a growth promoter on the occurrence of macrolide resistant enterococci and staphylococci in pigs. AB - This study was conducted to investigate the effect of tylosin used as a growth promoter on the occurrence of macrolide-resistant enterococci and staphylococci in pigs. Two identical feeding experiments with 10 pigs each were conducted to evaluate the effect of tylosin on the occurrence of erythromycin resistance among enterococci sampled from feces and Staphylococcus hyicus sampled by skin swabs. Half of the pigs were fed antibiotic-free feed and the other half feed with tylosin (30 microg/g) added. For each pig, weekly fecal samples and skin swabs were collected and examined for erythromycin-susceptible and erythromycin resistant enterococci and S. hyicus, respectively. There was an immediate effect of tylosin on the fraction of resistant enterococci recovered, increasing by a factor 2.4; the effect on S. hyicus was more gradual, increasing at a rate of about 8% per day and totaling a five-fold increase over 20 days. Thus, a clear effect on resistance occurrence was demonstrated, not only in intestinal bacteria, but also on bacteria sampled from the skin. PMID- 9988050 TI - Transmission of VanA-type vancomycin-resistant enterococci and vanA resistance elements between chicken and humans at avoparcin-exposed farms. AB - The genetical relatedness between epidemiologically linked fecal VRE strains from poultry farmers (n = 5) and their broilers (n = 7) at five avoparcin-exposed Norwegian farms was examined. Pulsed-field gel electrophoresis (PFGE) of bacterial chromosomal digests and structural analysis of vanA resistance elements was performed. Animal and human Enterococcus faecium strains at one farm were genetically closely related with indistinguishable vanA elements and a single band position difference in PFGE analysis. Examination of the vanA elements in genetically unrelated strains by restriction enzyme digestion of Tn1546 long-PCR amplicons and ORF2-vanR intergenic sequencing revealed a pool of at least two distinct vanA gene cluster groups in the two reservoirs. The results indicate that transmission of VanA glycopeptide resistance in enterococci between human and animal at avoparcin-exposed farms can occur by direct transfer of VRE strains as well as horizontal spread of resistance genes between strains. PMID- 9988051 TI - Antimicrobial resistance in staphylococci and enterococci in 10 Portuguese hospitals in 1996 and 1997. POSGAR. Portuguese Study Group of Antimicrobial Resistance. AB - During a 2-year period, 10 Portuguese hospitals located throughout the country studied antimicrobial susceptibilities of clinically relevant staphylococci and enterococci. Of more than 12,000 Staphylococcus aureus isolates tested, two main patterns were found, methicillin-sensitive organisms most of them resistant only to penicillin but a few to other antimicrobials and methicillin-resistant S. aureus (MRSA) strains (prevalence 48.2%) resistant to most of the antimicrobials tested and uniformly susceptible to vancomycin. Among coagulase-negative staphylococci (CNS), 71% of S. epidermidis (approximately 5,000 isolates tested) and 84% S. haemolyticus (approximately 1,000 isolates tested) were also resistant to methicillin as well as most other antimicrobials except vancomycin. Most of the 5,000 Enterococcus faecalis isolates tested were susceptible to ampicillin and vancomycin, in contrast to 650 E. faecium isolates, 70% of which were resistant to ampicillin and 20% to vancomycin and all other antibiotics. A high prevalence of aminoglycoside resistance occurred in both Enterococcus species. This survey showed that resistance profiles of staphylococci and enterococci hospital isolates have not changed in the last 5 years in Portugal, with the exception of the rise in vancomycin resistance in E. faecium. The high prevalence of methicillin resistance in S. aureus and in the CNS remains an issue of medical concern. PMID- 9988052 TI - Molecular characterization of penicillin-resistant Streptococcus pneumoniae isolates causing respiratory disease in the United States. AB - Three hundred twenty-eight (328) penicillin-resistant Streptococcus pneumoniae isolates collected in 39 states of the United States between October, 1996, and March, 1997, from (mostly adult) patients with respiratory disease were characterized by microbiological, serological, and molecular fingerprinting techniques, including determination of chromosomal macrorestriction pattern with pulsed-field gel electrophoresis (PFGE) and hybridization with DNA probes specific for various antibiotic resistance genes. The overwhelming majority of the isolates were in five serogroups (23, 6, 19, 9, 14). All isolates had penicillin MIC values of at least 2 microg/ml, but the collection also included isolates with MIC values as high as 16 microg/ml. Virtually all isolates (96.6%) were resistant to trimethoprim/sulfamethoxazole (SXT) and many isolates were also resistant to chloramphenicol (43%), tetracycline (55%), and erythromycin (65%). Resistance to levofloxacin was extremely rare. The molecular fingerprinting methods showed that a surprisingly large proportion (167 out of 328, or 50.9%) of the isolates belonged to two international epidemic clones of S. pneumoniae: clone A (127, or 38.7%) with properties indistinguishable from that of the 23F multiresistant "Spanish/USA" clone widely spread in Europe, Asia, Latin America, and South Africa, and clone B (40, or 12.2%) belonging to the "French" serogroup 9/14 clone widely spread in Europe and South America. Virtually all members of clone A were also resistant to chloramphenicol (cat+), tetracycline (tetM+), and SXT, and about 75% were also resistant to erythromycin (mefE+ or ermB+). Close to 30% (39 out of 127) of the clone A isolates expressed anomalous serotypes (primarily serotypes 19 and 14, and nontypable) and most likely represented spontaneous capsular transformants. Most of the 40 isolates (35/40) belonging to clone B expressed serotype 9, with five of the isolates expressing serotypes 14 or 19, or were nontypable. All members of this clone were resistant to penicillin and SXT with only occasional isolates showing resistance to macrolides, tetracycline, and chloramphenicol. The combination of microbiological tests and DNA hybridizations also allowed the identification of unusual strains, for instance, isolates that reacted with the tetM or mefE DNA probes without showing phenotypic antibiotic resistance, an isolate showing phenotypic macrolide resistance without hybridizing with either the ermB or mefE DNA probes, or isolates that hybridized with both of these DNA probes. In addition to clones A and B, another large portion of the S. pneumoniae isolates (112 of 328, or 34.1%) was represented by eight clusters, each with a unique PFGE type. These clusters, together with the clone A and clone B isolates, made up 85% of all the penicillin resistant isolates identified in this survey in the United States. Both international clones and the unique clusters showed wide geographic dispersal: Clone A was present in 30 of the 39 states and clone B in 18. The data suggest that the major mode of spread of penicillin-resistant pneumococci in the United States is by clonal expansion and that the most significant components (clones A and B) have been imported into the United States from abroad. PMID- 9988053 TI - Impact of antibiotic resistance on chemotherapy for pneumococcal infections. AB - Over the past three decades, penicillin-resistant pneumococci have emerged worldwide. In addition, penicillin-resistant strains have also decreased susceptibility to other beta-lactams (including cephalosporins) and these strains are often resistant to other antibiotic groups, making the treatment options much more difficult. Nevertheless, the present in vitro definitions of resistance to penicillin and cephalosporins in pneumococci could not be appropriated for all types of pneumococcal infections. Thus, current levels of resistance to penicillin and cephalosporin seem to have little, if any, clinical relevance in nonmeningeal infections (e.g., pneumonia or bacteremia). On the contrary, numerous clinical failures have been reported in patients with pneumococcal meningitis caused by strains with MICs > or = 0.12 microg/ml, and penicillin should never be used in pneumococcal meningitis except when the strain is known to be fully susceptible to this drug. Today, therapy for pneumococcal meningitis should mainly be selected on the basis of susceptibility to cephalosporins, and most patients may currently be treated with high-dose cefotaxime (+/-) vancomycin, depending on the levels of resistance in the patient's geographic area. In this review, we present a practical approach, based on current levels of antibiotic resistance, for treating the most prevalent pneumococcal infections. However, it should be emphasized that the most appropriate antibiotic therapy for infections caused by resistant pneumococci remains controversial, and comparative, randomized studies are urgently needed to clarify the best antibiotic therapy for these infections. PMID- 9988054 TI - A double-blind study of paroxetine, fluoxetine, and placebo in outpatients with major depression. AB - We report results from a multicenter, placebo-controlled, randomized, double blind comparison of the efficacy and tolerability of paroxetine and fluoxetine in outpatients with major depression. Across five U.S. sites, 128 outpatients (mean age: 41.3 +/- 12.6; 63 men and 65 women) with moderate to moderately severe major depression without a history of mania or hypomania were recruited between 1993 and 1994. All 128 patients completed a 1-week placebo washout period, and were then randomized to 12 weeks of double-blind treatment with paroxetine up to 50 mg/day (n = 55), fluoxetine up to 80 mg/day (n = 54), or placebo (n = 19). Subjects were evaluated weekly for the first 4 weeks, then at weeks 6, 9, and 12 with the 21-item HAMD and the Covi Anxiety Scale. There were no significant differences among the three treatment groups in baseline and endpoint depression and anxiety severity, as well as in the degree of depression and anxiety improvement. There were no statistically significant differences in rates or mean numbers of adverse events between paroxetine-treated patients and fluoxetine treated patients. In summary, our results, although limited by the lack of a significant difference from placebo in treatment outcome, suggest that the SSRIs paroxetine and fluoxetine have comparable antidepressant and antianxiety efficacies among depressed outpatients, as well as similar safety and tolerability profiles. PMID- 9988055 TI - Diagnostic stability of schizophrenia in psychiatric emergency room patients. AB - Diagnoses obtained from the hospital computer system were compared at two consecutive visits in 286 psychiatric emergency room patients within a 7-month period. Diagnostic agreement of schizophrenia and changes from and to schizophrenia were examined. There was moderate stability for a schizophrenic diagnosis in patients at two consecutive visits (kappa 0.5). schizophrenia was a more stable diagnosis in males (kappa 0.6) than females (0.4). Underdiagnosis of schizophrenia in females may be due to initial diagnostic confusion with affective illnesses. Further studies are needed in other settings to assess if underdiagnosis is associated with undertreatment of schizophrenia in females. PMID- 9988056 TI - PTSD following bereavement. AB - Until quite recently, the only stressor considered consistent with the diagnosis of PTSD was a catastrophic, out of the ordinary, trauma that almost anyone could be expected to have a severe reaction to. Thus, PTSD was considered relatively rare among non-military populations. More recently, epidemiologic surveys have suggested that PTSD may be much more prevalent than heretofore recognized, and the DSM-IV has opened the door to a much larger variety of stressors (the "A" criterion). Yet, bereavement is not considered the type of stressor capable of producing PTSD. In this study, 350 newly bereaved widows and widowers were assessed for the prevalence of PTSD, its chronicity, comorbidity, and consequences. The diagnosis of PTSD was made on the basis of questionnaire items approximating the DSM-IV criteria for PTSD. At 2 months after the spouse's death, 10% of those whose spouses died after a chronic illness met criteria for PTSD, 9% of those whose spouses died unexpectedly met criteria, and 36% of those whose spouses died from "unnatural" causes (suicide or accident) had PTSD. Symptoms tended to be chronic in at least 40% of the subjects, almost always were associated with comorbid depression, and created substantial morbidity. The results suggested that PTSD may occur after bereavement, and, by extension, other stressors not recognized by official diagnostic systems. The "A" criterion needs further examination. PMID- 9988057 TI - Clinical correlates of response to valproate in geriatric inpatients. AB - The efficacy of valproate for the management of adults with bipolar disorder has been repeatedly demonstrated in several studies. Patients with mixed states, rapid cycling, and EEG abnormalities have been shown to respond favorably to valproate. Valproate is also being increasingly used in disorders with aggressive or agitated features, such as the behavioral disorders of dementia; yet, few studies have documented the utility of valproate in geriatric patients. The need to document safe and effective pharmacologic agents to treat geriatric mood and behavioral disorders continues to increase with the growing elderly population. We conducted a retrospective study of the use of valproate in patients consecutively hospitalized over a 5-year period on a psychiatric unit. Thirty nine patients over age 60 were identified and then categorized into non-, partial, and full responders based on Clinical Global Impression ratings. Information on diagnosis, age, valproate dose and serum concentration, psychiatric symptoms, medical comorbidity, concurrent psychotropic medications, and side effects was collected. Results suggest that responders to valproate (full or partial) over the age of 60 years were more likely to be female, younger, carry a diagnosis of bipolar disorder, and achieve higher serum valproate concentrations. Full responders had fewer psychotic symptoms but usually displayed manic symptoms. The date of this study suggests the need for controlled clinical trials to clarify the utility and clinical predictors of response to valproate in the geriatric population. PMID- 9988058 TI - Suicide methods and presence of intoxicating abusable substances: some clinical and public health implications. AB - Toxicological studies have reported the presence of alcohol in about a third of suicides. Some have suggested that the presence of alcohol might predispose suicidal people to use particular methods, e.g., guns, although, in general, this does not appear to be the case. More recently, comprehensive toxicological studies have provided data on the detection of all intoxicating abusable substances (IAS) among suicides. The purpose of this report is to examine the presence of two samples of suicides to see if any relationships between presence of IAS at post mortem toxicology and any specific suicide method. The samples included 179 suicides from San Diego, California (1981-1982), and 225 suicides from Mobile, Alabama (1990-1995) for which comprehensive toxicological examination had been conducted. Methods were grouped into more immediately fatal (MIF) and less immediately fatal (LIF) categories. The most common method in each category (guns and overdoses respectively) were examined separately as well. The same proportions of men (51%) and women (65%) were positive for any IAS in both locations. There were no significant differences in the proportions of suicides that were positive for IAS between the sample totals or by gender or age groups (under age 30 and age 30 and over) for any of the methods or categories examined. Significantly more of the Mobile suicides were by MIF methods than in San Diego for both genders, almost totally attributable to the use of guns. The use of guns for suicide in Mobile (and the state of Alabama) was also significantly higher than the rest of the U.S. in the early 1990's. Nonetheless, the suicide rates for men and women in Mobile (and Alabama) were no higher than for the overall U.S. rates. We conclude that potentially suicidal people should be advised to avoid intoxicating abusable substances of any kind. We also suggest that physicians should avoid prescribing such substances to depressed or suicidal patients. PMID- 9988059 TI - Melancholia with onset during treatment with SSRIs. AB - A defined group of medical records was surveyed for patients who showed onset of major depression with melancholic features while taking an antidepressant medication. Nine cases resulted. In all the antidepressants being taken while melancholia began were SSRIs and the melancholic depression remitted rapidly with the first treatment given, bupropion in five males, nortriptyline with triiodothyronine in two females, and ECT in one male and one female. This suggests that patients who take SSRIs and are melancholic respond well to bupropion, nortriptyline, or ECT. These observations complement reports of low responsivity of melancholic depression to SSRIs and distinctions between melancholic and nonmelancholic depressions. PMID- 9988060 TI - Adjunctive tiagabine treatment of psychiatric disorders: three cases. AB - Anticonvulsants which effectively treat complex partial seizures are noted to have mood stabilizing effects (carbamazepine, valproate, lamotrigine, gabapentin). Tiagabine, a novel GABA uptake inhibitor anticonvulsant with similar indications, was used as adjunctive therapy to control psychiatric symptoms in three patients--two with bipolar disorder and one with schizoaffective disorder, bipolar type. All three patients improved during adjunctive low dosage tiagabine treatment and no untoward side effects were noted. Clinicians are advised to consider this new anticonvulsant as a potential adjunctive agent in the treatment of bipolar and schizoaffective disorders. Controlled trials are indicated. PMID- 9988061 TI - Rational treatment of panic disorder with antidepressants. AB - Rational treatment of panic disorders with antidepressants rests on decisions of drug choice, dosage, and duration of treatment. In this paper, we selectively review the author's research with the standard antidepressant, imipramine, in the treatment of panic disorder with agoraphobia as it relates to practical issues. We develop general guidelines for treatment, suggest researchable ways of increasing the net effectiveness of treatment with this class of drugs, and discuss limited generalizations to the extant literature on selective serotonin reuptake inhibitors in panic disorders. PMID- 9988062 TI - An ultrashort 1-day protocol of Tc-99m tetrofosmin. AB - PURPOSE: This study describes a new 1-day protocol with Tc-99m tetrofosmin that requires only 100 minutes to obtain both stress and resting cardiac images by using a double-injection and subtraction method. METHODS: This procedure was performed in 48 consecutive patients. Rest-rest double injections were performed in eight patients (five men, three women; mean age, 69 +/- 9.8 years ) to evaluate count and image reproducibility (subprotocol A), and stress-rest and additional resting perfusion images (true rest) were done on a different day in 11 patients (five men, six women; mean age, 63 +/- 5.9 years) to confirm the validity of the new protocol (subprotocol B). RESULTS: Image quality scores of the resting image were excellent (35 of 48, or 72.9%), good (7 of 48, or 14.6%), fair (3 of 48, or 6.3%), and poor (3 of 48, or 6.3%). The scintigraphic findings with the new protocol corresponded closely with those of angiography in 26 of 34 cases (76.5%), with a tendency for underestimation (in 5 of 34 cases, or 14.7%) rather than overestimation (in 3 of 34 cases, or 8.8%). In subprotocol A, count reproducibility between the two resting images was excellent (r = 0.95; P < 0.0001); and in subprotocol B, the early-rest images were concordant visually and quantitatively with the true rest images (r = 0.89, P < 0.0001). CONCLUSION: Although there are some limitations, this protocol can be used as a routine stress-rest protocol. PMID- 9988063 TI - Adenosine challenge and boost protocols: new tools for myocardial perfusion imaging. AB - The validity of pharmacologic stress testing and subsequent myocardial perfusion imaging is uncertain in those patients who may have taken caffeine within the 24 hours before testing. For such patients, two new challenge tests have been developed. An intravenous bolus dose of adenosine is given at a dose of 6 mg in a period of 1 or 2 seconds. A physiologic response qualifies the patient to proceed with the scheduled stress test. In the occasional patient who exhibits no pharmacologic symptoms during an infusion test, a similar bolus dose of 6 mg adenosine can validate perfusion tests. These two applications are successful regardless of whether adenosine or dipyridamole infusions are performed. Based on this multicenter experience over 4 years, the authors estimate that 5% to 10% of patients undergoing pharmacologic testing are appropriate candidates for a challenge test. PMID- 9988064 TI - Coronary artery occlusion and myocardial infarction: a seldom encountered complication of blunt chest trauma. AB - Myocardial infarction is a rare complication that can occur after blunt chest trauma. The authors describe a 30-year-old man who experienced a fatal anterolateral myocardial infarction after chest trauma in a motorcycle accident. The electrocardiogram and creatine phosphokinase-MB isoenzymes levels suggested myocardial necrosis. Tc-99m phosphate myocardial scintigraphy identified an extensive doughnut-shaped uptake over the cardiac area. An echocardiogram revealed severe left ventricular impairment. Coronary angiography confirmed complete occlusion of the proximal left anterior descending coronary artery. PMID- 9988065 TI - Dipyridamole modulated Tc-99m sestamibi lung SPECT in small cell lung cancer. AB - PURPOSE: In this study, the authors wanted to determine whether dipyridamole modulated MIBI (dipyridamole-MIBI) could enhance the prediction of the response to chemotherapy in patients with small cell lung cancer. METHODS: Twenty-seven patients with biopsy-proved small cell lung cancer (25 men, 2 women; mean age, 61 +/- 7 years) underwent dipyridamole-MIBI SPECT 3 to 7 days before starting chemotherapy (80 mg/m2 etoposide and 80 mg/m2 cisplatin every 3 or 4 weeks for at least two cycles). Tomographic images before and after dipyridamole (0.84 mg/kg) were acquired 1 hour after injection of 370 (10 mCi) and 1,110 (30 mCi) MBq MIBI, respectively. The response to chemotherapy was grouped as specified as complete response (CR), partial (PR), no change (NC), or progressive disease (PD), according to the change in tumor size on chest roentgenography and CT. Patients showing CR and PR were classified as responders, and those who showed NC and PD were considered nonresponders. RESULTS: Among the 27 patients, 22 were responders (3 CR, 19 PR) and 5 were nonresponders (3 NC, 2 PD). The tumor-to-normal lung ratio (T:NL) of responders was significantly higher than that of nonresponders. The diagnostic accuracy of the T:NL ratio to differentiate responders and nonresponders was 33.3%, with a cutoff value of 2.5, which was significantly improved to 77.8% when an increased T:NL ratio after dipyridamole was assigned to a nonresponder. Furthermore, all patients with CR showed diminished T:NL ratios after dipyridamole, and all patients with NR showed an increased T:NL ratio after dipyridamole. CONCLUSION: Dipyridamole-MIBI SPECT could enhance the prediction of response to chemotherapy in patients with small cell lung cancer. PMID- 9988066 TI - Laparoscopy as a cause of a false-positive Meckel's scan. AB - A new cause of a false-positive result of a Meckel's scan is reported. An 11-year old girl had a 3-week history of constant right lower quadrant pain that was initially managed by laparoscopic appendectomy. A repeated laparoscopy for persistent pain was nondiagnostic. A missed Meckel's diverticulum was considered as the cause of this pain, which prompted a Meckel scan. This scan revealed a periumbilical focus of activity that was interpreted as a Meckel's diverticulum attached to the anterior abdominal wall by a band. The laparotomy showed no Meckel's diverticulum. The false-positive result of the Meckel scan may be the result of inflammation from the periumbilical laparoscopic port site. PMID- 9988067 TI - Increased pertechnegas lung clearance in interstitial lung disease. AB - BACKGROUND: Interstitial lung disease (ILD) is characterized by inflammation within the alveolar walls and interstitium of the lungs. This causes increased alveolar-capillary membrane permeability. The diagnosis is made by clinical features, chest roentgenography, lung function tests, and high-resolution CT, and it is confirmed by lung biopsy. Radionuclide aerosol tracers such as Tc-99m DTPA show increased lung clearance in ILD. The clearance rate of microaerosol pertechnegas (modified Technegas) from the lungs in the assessment of ILD was evaluated. METHODS: Thirty-two patients (22 with ILD and 10 with non-ILD) were evaluated with pertechnegas. Pertechnegas is formed by adding 3% oxygen to technegas, a microaerosol ventilation agent. Regions of interest were then drawn around the lungs, and clearance rates were determined from the best exponential fit. RESULTS: The mean clearance rate of pertechnegas was significantly increased in ILD and measured 5.78 +/- 2.2 minutes compared with non-ILD, which measured 8.53 +/- 2.42 minutes (P < 0.001). The sensitivity and specificity rates of pertechnegas clearance (less than 8 minutes) in ILD were 90% and 60%, respectively. When combined with chest roentgenography, the sensitivity and specificity rates increased to 100% and 90%, respectively. CONCLUSIONS: Pertechnegas is highly effective in determining the presence of active ILD. It differentiates between active ILD and non-ILD, and it is highly sensitive and specific when combined with chest roentgenography. Its potential role in the management of ILD merits further investigation. PMID- 9988068 TI - Recurrent ectopic adrenocorticotropic hormone producing thymic carcinoid detected with octreotide imaging. AB - Primary thymic carcinoids are rare tumors in which the tumor cells retain functional somatostatin receptors. In-111-labeled octreotide imaging has been used to diagnose abdominal carcinoids with a sensitivity rate of approximately 87%. The authors describe a case of a recurrent, ectopic cortisol-releasing hormone that produced thymic carcinoid localized as a focal area of increased activity in the upper mediastinum when planar and tomographic octreotide scintigraphy was used. Chest CT and MRI failed to localize the tumor. This may be the first reported case of In-111-labeled octreotide used to identify Cushing's syndrome caused by a cortisol-releasing hormone that produced thymic carcinoid. PMID- 9988069 TI - Detection of abscesses with Tc-99m HMPAO leukocyte scintigraphy depends on their stage and location. AB - Two abscesses were shown on CT in a 72-year-old man: one in the left hip and one in the left pelvic region that resulted from a motor vehicle collision that occurred 8 months earlier. Bone scintigraphy showed increased uptake in the left hip area. On Tc-99m HMPAO leukocyte imaging, the hip area appeared to be photopenic, and the abscess of the left pelvis was not identified. Incidental uptake in the left lung base appeared to be an active acute inflammatory process as evidenced by an infiltrating lesion in the left lower lung on a chest radiograph. Because leukocyte scintigraphy cannot detect the presence of a chronic inflammatory process in the absence of acute inflammatory cells, the patient's abscesses in the left hip and the left pelvis did not localize Tc-99m HMPAO-labeled neutrophils. The cold lesion in the left hip area was most likely caused by the lesion in the reticuloendothelial system (bone marrow); the unidentifiable pelvic lesion was related to the area(s) outside the reticuloendothelial system. In interpreting a labeled leukocyte image, clinicians should be alert to the stage (chronic or acute) and location (regardless of whether in the reticuloendothelial system) of infectious lesion(s). In this patient, a wide spectrum of manifestations was evident on leukocyte scintigraphy. PMID- 9988070 TI - Tc-99m sestamibi scintigraphy in multiple myeloma. AB - Tc-99m sestamibi imaging was performed in two patients with multiple myeloma. Focal areas of increased uptake in one patient and diffuse skeletal uptake in the second patient were found. Tc-99m sestamibi appears to identify bone marrow and osteolytic involvement in multiple myeloma. PMID- 9988071 TI - I-131 orthoiodohippurate assessment of renal function after heart transplantation. AB - PURPOSE: The authors studied the relation between cardiac output (CO) and effective renal plasma flow (ERPF) and compared values from control patients with various cardiac problems with those in a group of study patients who had undergone heart transplantation. METHODS: The experimental group was divided into three subgroups according to the interval between the time of surgery and the time of the CO-ERPF studies. Group 1 consisted of patients studied fewer than 10 days after surgery; group 2 consisted of patients studied 10 to 20 days after operation; and group 3 consisted of patients studied more than 20 days after operation. Effective renal plasma flow was determined by the single-injection, single plasma sample method, where 50 microCi I-131 orthoiodohippurate was injected intravenously in a single dose and plasma concentrations of radioactivity were determined. The quotient of injected dose radioactivity divided by plasma radioactivity is highly predictive of global ERPF. Cardiac output was measured by thermodilution. RESULTS: In the control group, a positive linear correlation was found between CO and ERPF; however, the CO:ERPF ratio was elevated, and after heart transplantation, a lag time was observed for as long as 3 weeks in some patients before CO:ERPF ratios returned to control group levels. The regression equation and standard error for the control group was CO = 1.85 + 0.0065 ERPF (+/-0.62) l/min versus 1.433 + 0.0068 ERPF (+/-0.64) l/min for group 3. The correlation coefficients comparing CO with ERPF were r = 0.88, 0.23, 0.51, and 0.85, for the control group and groups 1, 2, and 3, respectively. CONCLUSION: A localized release of catecholamines from the adrenal gland is proposed to cause ERPF damping after abrupt increases in CO. PMID- 9988072 TI - Tc-99m DTPA renal scintigraphy using deconvolution analysis with six functional images of the mean time to evaluate acute pyelonephritis. AB - In 38 children with proved P-fimbriated Escherichia coli acute pyelonephritis, Tc 99m DTPA dynamic renal scintigraphy in the zoom mode using deconvolution analysis was performed, and the results were compared with those of Tc-99m DMSA scans. From the dynamic study, six functional images of the mean time were generated. Each functional image was analyzed separately to search for focal areas of increased mean time within the kidney contour, especially over the kidney parenchyma. Time-activity curves from these areas were generated and analyzed. Tc 99m DMSA scintigraphy showed generalized or focal decreased uptake in 32 (41.8%) kidneys, and deconvolution analysis of Tc-99m DTPA scintigraphy revealed pathologic renographic curves in 58 (77.6%) kidneys. Prolonged whole-kidney and normal renal parenchymal transit times (dilatation without obstruction) were found in 38 (50%) kidneys, whereas prolonged whole-kidney and renal parenchymal transit times (dilatation with obstruction) were observed in 20 (27.6%) kidneys. Separate analysis of each of the six functional images of the mean time showed focal areas of increased mean time in the kidney parenchyma of 11 kidneys. In five cases, time-activity curves from these areas showed a sharp increase of activity on the descending part of the curve, which might reflect the return of urine from the collecting system into kidney cortex (i.e., intrarenal reflux). These results showed that in a urinary tract with acute pyelonephritis, urodynamic changes may lead to obstructive nephropathy and intrarenal reflux. Tc 99m DTPA renal scintigraphy in the zoom mode using deconvolution analysis with six functional images of the mean time has proved to be a valuable method to evaluate acute pyelonephritis, thus allowing dynamic and morphologic analysis of the urinary tract at the same time. PMID- 9988074 TI - In-111-labeled leukocyte infection imaging: false-positive results caused by wound dressing and hematoma. PMID- 9988073 TI - The painful accessory navicular bone: scintigraphic and radiographic correlation. PMID- 9988075 TI - Scintigraphic intervention in a lung scan confirming a large hiatal hernia. PMID- 9988076 TI - False-negative FDG PET imaging in a patient with metastatic melanoma and ileal intussusception. PMID- 9988077 TI - Indium-111 pentetreotide scintigraphy of mesenchymal tumor with oncogenic osteomalacia. PMID- 9988078 TI - Pedunculated giant liver hemangioma mimicking a hypervascular gastric tumor on Tc 99m RBC SPECT. PMID- 9988079 TI - Pedunculated hepatic hemangioma identified on Tc-99m DTPA-HSA scintigraphy. PMID- 9988080 TI - Old traumatic ventricular septal defect seen on myocardial perfusion imaging. PMID- 9988081 TI - Increased fluorine-18 fluorodeoxyglucose uptake in the right atrial wall in a patient with atrial fibrillation. PMID- 9988082 TI - Displaced urinary bladder creating an unusual pattern on bone scan mimicking disease. PMID- 9988083 TI - Muscle metastasis from lung cancer detected by Ga-67 scintigraphy. PMID- 9988084 TI - An "upside-down" liver and gallbladder discovered on hepatobiliary scan. PMID- 9988085 TI - Current readings in nuclear medicine. PMID- 9988086 TI - Pesticides and congenital malformations--how many studies will it take to reach a conclusion? PMID- 9988087 TI - Work-related low-back problems in nursing. AB - This scientific literature review focuses on the relation between nursing work and low-back problems. Its aim was to estimate the risk of physical, psychosocial, and work organizational exposure factors that may lead to low-back problems. In addition this paper reviews and evaluates reported ergonomic intervention, with the object of decreasing the prevalence and incidence of low back problems among nurses. A considerable number of studies of nursing staff has shown the connection between lifts and transfers of patients on one hand and low back problems on the other. Factors in nursing work that may be significant in this connection are staff density and work satisfaction. In this review the single individual factor that was indisputably related to low-back problems was "history of back problems". Prevention programs do not show unequivocally positive results. There is a great need to carry out prospective studies with preventive programs. PMID- 9988088 TI - Workplace factors and care seeking for low-back pain among female nursing personnel. MUSIC-Norrtalje Study Group. AB - OBJECTIVES: Low-back pain is common among nursing personnel, and its origin is multifactorial. The present study focused on physical and psychosocial work load. The objectives of the study were to estimate the relative risk for nursing personnel, compared with other occupational groups, to seek health care for low back pain, and to identify risk factors. METHODS: This study is a part of a population-based case-referent study in the municipality of Norrtalje, situated north of Stockholm. Altogether 333 women served as cases and 733 served as referents. Eighty-one cases and 188 referents were employed in nursing work. The cases had sought health care for low-back pain during the study period, November 1993 to November 1996. The referents were randomly selected from the same population. The subjects filled out 2 questionnaires and participated in interviews about physical exposures and psychosocial factors. RESULTS: When the female nursing personnel were compared with other employed women, no increased risk of consultation for low-back pain was found. According to a multivariate logistic regression, nursing personnel exposed to forward-bending working positions, high energetic work load, perceived physical exertion, or insufficient social support had the highest risk estimates. In univariate analyses, the combination of physical and psychosocial risk factors was associated with a particularly high risk. CONCLUSIONS: In nursing work, physical load seems to be more significant than psychosocial factors when a worker seeks health care for low-back pain. The results of did not support the hypothesis that nursing work is a risk occupation for seeking care for low-back pain when compared with other occupations. PMID- 9988089 TI - Paternal exposure to pesticides and congenital malformations. AB - OBJECTIVES: A case-referent study with 261 matched pairs was carried out in 8 hospitals of Comunidad Valenciana, Spain, to assess the relation between occupational exposure to pesticides and selected congenital malformations. In this paper, the results concerning paternal exposure are presented. METHODS: The parents of the case patients and the referents were interviewed to collect information about exposure to pesticides and potential confounding variables. Detailed information on direct involvement in the handling of pesticides was collected for the interviewees involved in agricultural activities during a previously defined period in relation to conception and pregnancy. Exposure data were reviewed by 2 experts who assigned ordinal scores for the probability and intensity of exposure to pesticide classes and active ingredients. RESULTS: The dichotomous analysis of exposure (absent, present) yielded some increased risks, although not statistically significant, for aliphatic hydrocarbons [adjusted odds ratio (adjusted OR) 2.05, 95% confidence interval (95% CI) 0.62-6.80], inorganic compounds (adjusted OR 2.02, 95% CI 0.53-7.72), and glufosinate (adjusted OR 2.45, 95% CI 0.78-7.70), and a significant association for pyridil derivatives (adjusted OR 2.77, 95% CI 1.19-6.44). The analysis based on the experts' scores (2 levels of exposure) showed some consistent associations for these compounds. CONCLUSIONS: This research indicates a possible risk of congenital malformations for paternal exposure to some pesticides, notably, pyridils, aliphatic hydrocarbons, inorganic compounds, and glufosinate. It did not find an increased risk for paternal exposure to pesticides in the classes of organophosphates, carbamates, organochlorines, chloroalkylthio fungicides and organosulfurs. These findings warrant further investigation. PMID- 9988090 TI - Particle-bound benzene from diesel engine exhaust. AB - OBJECTIVES: The large surface area of the carbon core of diesel exhaust particles may contribute to the adsorption or condensation of such volatile carcinogenic organic compounds as benzene. The attention of this study focused on determining the distribution of benzene between the gas and particulate phases in the breathing zone of bus garage workers. METHODS: Benzene and suspended particulate matter were evaluated jointly in the air of a municipal bus garage. Personal passive monitors were used for benzene sampling in the breathing zone of the workers. Active samplers were used for sampling diesel exhaust particles and the benzene associated with them. The benzene levels were measured by gas chromatography. RESULTS: Diesel engine exhaust from buses was the main source of air pollution caused by benzene and particles in this study. The concentration of benzene in the gas and particulate phases showed a wide range of variation, depending on the distance of the workplace from the operating diesel engine. Benzene present in the breathing zone of the workers was distributed between the gas and particulate phases. The amounts of benzene associated with particles were significantly lower in summer than in winter. CONCLUSIONS: The particulate matter of diesel exhaust contains benzene in amounts comparable to the concentrations of carcinogenic polycyclic aromatic hydrocarbons (PAH) and the usually found nitro PAH. The concentration of benzene in the gas phase and in the suspended particulate matter of air can serve as an additional indicator of exposure to diesel exhaust and its carcinogenicity. PMID- 9988091 TI - Association between diesel exposure at work and prostate cancer. AB - OBJECTIVES: The possible etiologic relevance of occupational factors such as cadmium, cutting oils, diesel fuel and fumes, herbicides, polycyclic aromatic hydrocarbons (PAH), polychlorinated biphenyls, soot, tar, mineral oil, and solvents to prostate cancer was studied. METHODS: A case-referent study design was used to recruit 192 subjects with histologically confirmed prostate cancer and 210 referents who had prostate cancer histologically excluded either in one of two urologic practices (Hamburg and Frankfurt) or in the urological policlinic of the Frankfurt University. Data were gathered with a self-administered questionnaire and analyzed using logistic regression to control for age, region, and cigarette smoking. A job-exposure matrix was used for assigning exposure. For the calculation of dose-years, the duration of contact with specific substances was weighted by the intensity and probability of exposure according to a job exposure matrix. RESULTS: The analysis of dose-years yielded a statistically significant association between occupational exposure to diesel fuel or fumes and prostate cancer (odds ratio 3.7, 95% confidence interval 1.4-9.8, for subjects exposed to more than 25 dose-years in a comparison with subjects never exposed). For the other substances, no statistically significant differences in exposure were found between the cases and referents. When only jobs with a high exposure probability were used to classify the participants as exposed, only exposure to PAH was significantly associated with prostate cancer. CONCLUSIONS: In keeping with results from other studies, this study provides further evidence that exposure to diesel fuel or fumes - possibly mediated through PAH - may be associated with the development of prostate cancer. PMID- 9988092 TI - Vibrotactile sense in the hand-arm vibration syndrome. AB - OBJECTIVES: The purpose of this study was to investigate disturbances of the vibrotactile sense and their relation to clinical symptoms and findings among male symptomatic workers suffering from the hand-arm vibration syndrome. METHODS: Ninety-six such patients were interviewed and given a clinical and tactilometric examination. The symptoms were classified according to the Stockholm Workshop Scale. A sensibility index was used to quantify vibrotactile sense in the tactilogram. RESULTS: An abnormal sensibility index (<0.8) was recorded for 57.3% of the patients (mean of 4 fingers), at least 1 finger being abnormal in 72.9% of the patients. The sensibility index did not statistically differ between the patients suffering from sensorineural symptoms and those with vibration white finger. The stages of sensorineural symptoms, according to the Stockholm Workshop Scale, corresponded with the sensibility index, whereas the stages of vibration white finger did not. There were significant differences in the sensibility index between the fingers, between the right and left hands, and between the fingers innervated by the ulnar and median nerves. Bilateral symptoms and cold intolerance were associated with considerable impairment of the vibrotactile sense. Clinical median nerve involvement in the carpal tunnel was not reflected by the sensibility index. CONCLUSIONS: There is a considerable degree of neural involvement in all symptomatic vibration-exposed patients irrespective of symptoms. As symptoms progress, the severity of sensorineural symptoms, but not of vibration white finger, is reflected by the sensibility index. Cold intolerance is strongly related to nervous involvement and should be noted in the patient history. Tactilometry should be performed on 1 median and 1 ulnar nerve innervated finger of both hands, as an examination of 1 finger alone may be misleading. PMID- 9988093 TI - Powered dust respirator helmets in the prevention of occupational asthma among farmers. AB - OBJECTIVES: This study investigated the value of powered dust respirator helmets in the treatment of farmers with occupational asthma. METHODS: The study population consisted of 33 asthmatic agricultural workers, 24 with occupational asthma induced by cow dander or grains, 2 with other forms of atopic asthma, and 7 with nonatopic asthma. The efficiency of a powered dust respirator helmet with a P2-class filter in preventing asthmatic symptoms was assessed for 1 year. Morning and evening peak expiratory flow rates and daily symptoms of the subjects were monitored for 3 months without the use of the helmet and for 10 months with the helmet. RESULTS: Objective evidence of protection was obtained for farmers with occupational asthma. The morning peak flow rate increased and the variation in daily peak flow rate and the symptoms of cow-barn rhinitis diminished significantly during the helmet period. In the group of farmers with nonatopic asthma there was no improvement in peak flow rate or symptoms of asthma, although some of these farmers also seemed to benefit from helmet use. CONCLUSIONS: The results of this study suggest that especially dairy farmers with occupational asthma benefit from the use of a powered dust respirator helmet. PMID- 9988094 TI - The expression of neuropeptide-induced excessive grooming behavior in dopamine D1 and D2 receptor-deficient mice. AB - Grooming behavior in rodents has long been related to dopamine receptors in the brain. However, the relative contribution of dopamine D1-like receptors (D1 and D5) and D2-like receptors (D2, D3 and D4) in this behavior has not been established yet. Spontaneous novelty-induced grooming (as assessed with a 30-min sampling test) was reduced in knockout mice lacking the dopamine D1, receptor. Furthermore, the intracerebroventricular (i.c.v.) injection of small quantities of oxytocin, prolactin or the adrenocorticotrophic hormone 1-24 fragment, ACTH-(1 24) was followed by a diminished level of novelty-induced excessive grooming. These neuropeptides caused a sustained increase in grooming level of control animals (wild type). Interestingly, the i.c.v. injection of beta-endorphin enhanced novelty-induced grooming to a level similar in control and knockout mice. The systemic administration of the dopamine D2 receptor antagonist, sulpiride did not suppress the residual grooming activity shown by animals injected with oxytocin, prolactin or ACTH-(1-24), and did not change the behavioral expression of those injected with beta-endorphin. In contrast, the systemic administration of the opioid receptor antagonist, naloxone, totally suppressed the residual grooming activity of oxytocin-, prolactin- or ACTH-(1-24) injected mice and of those treated with beta-endorphin. In contrast with the behavioral deficit observed in dopamine D1 receptor-deficient mice, dopamine D2 receptor-null animals showed a normal expression of spontaneous novelty-induced grooming and a high level of grooming activity induced by i.c.v. injection of oxytocin, prolactin, ACTH-(1-24) or beta-endorphin. Again, the peripheral injection of naloxone was followed by a suppression of neuropeptide-induced excessive grooming in these animals. These data suggest that dopamine D1 receptors are involved in the expression of novelty-induced grooming in mice. In contrast, dopamine D2 receptors seem not to be important for the expression of this behavior. Furthermore, neuropeptide-enhanced grooming involves dopamine D1, but not dopamine D2 receptors. However, neurotransmitters other than dopamine (e.g., endorphins) may play a supplementary role in neuropeptide-enhanced grooming in mice. PMID- 9988095 TI - Chronic (-)-delta9-tetrahydrocannabinol treatment induces sensitization to the psychomotor effects of amphetamine in rats. AB - Clinical and basic research studies have linked cannabinoid consumption to the onset of psychosis, specially schizophrenia. In the present study we have evaluated the effects of the natural psychoactive constituent of Cannabis (-) delta9-tetrahydrocannabinol on the acute actions of the psychostimulant, D amphetamine, on behaviour displayed by male rats on a hole-board, a proposed animal model of amphetamine-induced psychosis. Cannabinoid-amphetamine interactions were studied (1) 30 min after acute injection of (-)-delta9 tetrahydrocannabinol (0.1 or 6.4 mg/kg, i.p.); (2) 30 min after the last injection of 14-daily treatment with (-)-delta9-tetrahydrocannabinol (0.1 or 6.4 mg/kg) and 3) 24 h after the last injection of 14-daily treatment with (-)-delta9 tetrahydrocannabinol (6.4 mg/kg). Acute cannabinoid exposure antagonized the amphetamine-induced dose-dependent increase in locomotion, exploration and the decrease in inactivity. Chronic treatment with (-)-delta9-tetrahydrocannabinol resulted in tolerance to this antagonistic effect on locomotion and inactivity but not on exploration, and potentiated amphetamine-induced stereotypies. Lastly, 24 h of withdrawal after 14 days of cannabinoid treatment resulted in sensitization to the effects of D-amphetamine on locomotion, exploration and stereotypies. Since (-)-delta9-tetrahydrocannabinol is a cannabinoid CB1 receptor agonist, densely present in limbic and basal ganglia circuits, and since amphetamine enhances monoaminergic inputs (i.e., dopamine, serotonin) in these brain areas, the present data support the hypothesis of a role for the cannabinoid CB1 receptor as a regulatory mechanism of monoaminergic neuron mediated psychomotor activation. These findings may be relevant for the understanding of both cannabinoid-monoamines interactions and Cannabis-associated psychosis. PMID- 9988096 TI - Stereoselective mu- and delta-opioid receptor-related antinociception and binding with (+)-thebaine. AB - In vivo and in vitro binding studies with natural thebaine and its enantiomer, (+)-thebaine were conducted to elucidate further their interactions with the opioid system. (-)-Thebaine a key intermediate in the biosynthesis of morphine in the poppy plant (Papaver somniferum) and in mammalian tissue, was poorly effective antinociceptively in mice at doses to 30 mg/kg. Its principal behavioral manifestation was lethal convulsions. Naltrindole, at doses of 1 and 10 mg/kg did not block either the convulsions or lethal effects, suggesting that the delta-opioid receptor system was not involved in this action. Surprisingly, the dextrorotatory isomer exhibited significant antinociceptive activity in the tail-flick [ED50 = 8.9 (3.4-22.1) mg/kg], hot-plate [ED50 = 22.9 (10.9-48.1) mg/kg] and phenylquinone [ED50) = 1.9 (1.6-9.5) mg/kg] assays. Studies with opioid receptor-subtype antagonists, beta-funaltrexamine, nor-binaltorphimine and naltrindole, indicated that antinociception was associated with mu- and delta opioid receptors. Results of displacement experiments supported the in vivo data. Significant competition for [3H]diprenorphine binding with both isomers for cloned mu- and delta-opioid receptors was observed. However, (-)-thebaine was more effective at the delta-opioid receptor (Ki = 1.02+/-0.01 microM) whereas (+) thebaine was more effective at the mu-opioid receptor ( Ki = 2.75+/-0.01 microM). Opioid-induced antinociception associated with unnatural thebaine raises the possibility of additional mu- and delta-opioid receptor sites. PMID- 9988097 TI - The involvement of opioidergic and noradrenergic mechanisms in nefopam antinociception. AB - Nefopam is a clinically effective analgesic agent used to control mild to moderate pain, whose mechanism of action is unknown. We have investigated the antinociceptive activity of nefopam in the mouse abdominal constriction assay and tail immersion test (48 degrees C). Nefopam was found to possess a high degree of potency against acetic acid-induced visceral nociception (ED50 2.5 mg kg(-1)). In the presence of the opioid receptor antagonists, naloxone or naltrindole, the resulting nefopam dose-response relationships were shifted to the right. Naloxone or naltrindole had no effect upon aspirin (ED50 32.1 mg kg(-1)) or clonidine (ED50 0.061 mg kg(-1)) induced antinociception. Acetorphan (10 mg kg(-1); s.c.), an inhibitor of neutral endopeptidase (EC 3.4.24.11) was able to potentiate nefopam's antinociceptive activity (ED50 1.5 mg kg(-1)). The alpha2-adrenoceptor antagonist, 2-[2-(2-methoxy-1,4-benzodioxanyl)]imidazoline hydrochloride (RX821002; 1 mg kg(-1); s.c.), shifted the dose-response curves for clonidine (ED50 7.1 mg kg(-1)) and nefopam (ED50 5.3 mg kg(-1)) to the right in this assay. Additionally, centrally administered RX821002 (1 microg/5 microl/animal; i.c.v.) reduced both clonidine (ED50 7.2 mg kg(-1)) and nefopam's ED50 15.5 mg kg(-1)) efficacy in the abdominal constriction assay. Nefopam (3 and 7.5 mg kg(-1); s.c.) produced significant antinociceptive effect in the thermal assay. Aspirin and RX821002 were devoid of any significant activity in the tail immersion test. Nefopam was shown to possess RX821002-reversible antinociceptive activity in both the tail immersion test and the abdominal constriction assay. These data suggest the involvement of an opioidergic and noradrenergic component to nefopam's antinociceptive activity in the mouse abdominal constriction assay and tail immersion test. However, the present results are unable to determine if the opioidergic component of nefopam antinociception is through a direct and/or indirect activation of opioid receptors. PMID- 9988098 TI - Effects of morphine in rats withdrawn from repeated nifedipine administration. AB - The effects of withdrawal from repeated nifedipine treatment on morphine-induced analgesia, hyperthermia and catalepsy as well as on cerebral [3H]nitrendipine binding and on morphine-induced changes in striatal and limbic dopamine and 5 hydroxytryptamine metabolism were studied in rats. Repeated administration of nifedipine (5 mg/kg i.p., twice daily for 14 days) decreased [3H]nitrendipine binding in several brain areas of the rats at 24 h after the last dose but did not change the nociceptive response or rectal temperature of the animals. Further, the antinociceptive potency of acute morphine (2.5 mg/kg s.c.) was significantly reduced in rats withdrawn for 24 h from repeated nifedipine treatment. However, withdrawal from repeated nifedipine treatment failed to affect either the hyperthermia induced by this dose of morphine or the catalepsy and the elevation of dopamine or 5-hydroxytryptamine metabolites induced by 15 mg/kg of morphine. Taken together, these data show that withdrawal from repeated treatment with dihydropyridine calcium channel antagonists selectively reduces the effects of opioids on the nociceptive response. PMID- 9988099 TI - Chronic alnespirone-induced desensitization of somatodendritic 5-HT1A autoreceptors in the rat dorsal raphe nucleus. AB - The effects of long-term (7, 14 or 21 days) administration of the 5-HT1A receptor agonist alnespirone [5 mg/(kg day), i.p.] on the binding characteristics of 5 HT1A, 5-HT2A and 5-HT3 receptors, and the functional status of 5-HT1A autoreceptors were assessed using biochemical and electrophysiological approaches in rats. Whatever the treatment duration, the specific binding of [3H]8 hydroxy-2 (di-n-propylamino)tetralin ([3H]8-OH-DPAT), [3H]trans,4-[(3Z)3-(2 dimethylaminoethyl) oxyimino-3(2-fluorophenyl) propen-1-yl] phenol hemifumarate ([3H]SR 46349B), and [3H]S-zacopride to 5-HT1A, 5-HT2A and 5-HT3 receptors, respectively, were unaltered in all the brain areas examined. In contrast, in vitro electrophysiological recordings performed 24 h after the last injection of alnespirone showed that the potency of the 5-HT1A receptor agonist, 8-OH-DPAT, to depress the firing of serotoninergic neurons in the dorsal raphe nucleus, was significantly reduced after a 21-day treatment with alnespirone. However, no changes were noted after a 7-day or 14-day treatment. These data indicate that desensitization of somatodendritic 5-HT1A autoreceptors is a selective but slowly developing adaptive phenomenon in response to their chronic stimulation in rats. PMID- 9988100 TI - A heroin-, but not a cocaine-expecting, self-administration state preferentially alters endogenous brain peptides. AB - The purpose of the current study was to assess neuropeptidergic alterations during a phase of the drug addiction cycle associated with drug craving as compared to a time period when the drug had been recently self-administered. Male Wistar rats were allowed to self-administer cocaine, heroin or saline for 6 h for 5 consecutive days. Immediately following the last self-administration session ('acute drug on board' state), and just before the next scheduled session ('drug expecting' state), the animals were decapitated and the levels of dynorphin A and B, [Met5]- and [Leu5]-enkephalin and substance P were measured in different brain areas. During the 'acute drug on board' state, peptide levels in animals that self-administered heroin or cocaine were not significantly changed. In contrast, during the 'drug expecting' state, heroin-treated animals had increased levels of dynorphin A, dynorphin B and [Met5]-enkephalin in the caudal striatum as compared to the cocaine- and saline-treated animals, and the level of [Leu5]-enkephalin was increased as compared to the cocaine-treated group. In the septum, an increase of [Met5]-enkephalin and substance P was observed in the animals expecting heroin as compared to the saline- and/or cocaine-treated animals. In the caudal striatum, substance P levels were elevated in the heroin- and cocaine expecting animals. In conclusion, heroin, as compared to cocaine, appears to have a more pronounced effect on dynorphin, enkephalin and substance P levels in the caudal striatum and septum, especially during periods when self-administration of the drug is expected. PMID- 9988101 TI - Methamphetamine alters prodynorphin gene expression and dynorphin A levels in rat hypothalamus. AB - Chronic administration of morphine or cocaine affects opioid gene expression. To better understand the possible existence of common neuronal pathways shared by different classes of drugs of abuse, we studied the effects of methamphetamine on the gene expression of the opioid precursor prodynorphin and on the levels of peptide dynorphin A in the rat brain. Acute (6 mg/kg, intraperitoneally, i.p.) and chronic (6 mg/kg, i.p. for 15 days) methamphetamine markedly raised prodynorphin mRNA levels in the hypothalamus, whereas no effect was observed in the hippocampus. Dynorphin A levels increased after chronic treatment in the hypothalamus and in the striatum, whereas no significant changes were detected after acute treatment. These results indicate that methamphetamine affects prodynorphin gene expression in the hypothalamus, which may be an important site (also for its relevant neuroendocrine correlates) for opioidergic mechanisms activated by addictive drugs. PMID- 9988102 TI - Comparison of the efficacy of glibenclamide and glimepiride in reperfusion induced arrhythmias in rats. AB - The effect of glibenclamide and glimepiride, two orally active antidiabetic sulphonylurea derivatives, was investigated on the development of reperfusion induced arrhythmias and it was compared to their blood glucose lowering action. Arrhythmias were produced by reperfusion following 6 min coronary artery ligation in anaesthetised rats. Glimepiride pretreatment (0.001-0.01-0.1-5.0 mg/kg i.p., 30 min before coronary occlusion) significantly decreased the incidence of irreversible ventricular fibrillation and increased the survival rate during reperfusion (64%, 61%, 60%, and 67% vs. 27% in controls). Glibenclamide produced similar effect (81% survival) only in a dose of 5 mg/kg, while smaller doses were ineffective. The minimal hypoglycaemic dose and the dose required to inhibit significantly the oral glucose loading-induced hyperglycaemia were similar (1 and 0.1 mg/kg, respectively) after glibenclamide and glimepiride. It is concluded that although the blood glucose lowering potency of glibenclamide and glimepiride is rather similar, glimepiride appears to be more potent than glibenclamide in preventing reperfusion-induced cardiac arrhythmias. PMID- 9988103 TI - Mechanisms involved in the vasorelaxant effect of (-)-stepholidine in rat mesenteric small arteries. AB - The purpose of the present investigation was to clarify whether the hypotensive action of the protoberberine alkaloid, and dopamine receptor antagonist, (-) stepholidine, can be ascribed to an effect on peripheral small arteries. For this purpose isolated mesenteric small arteries were suspended in microvascular myographs for isometric tension recording. Relaxations mediated by dopamine D1 receptors were antagonized by (-)-stepholidine. (-)-Stepholidine inhibited in a concentration-dependent manner the contractile responses evoked by noradrenaline (10(-6) M), but not the contractile responses evoked by depolarizing solution (KCl, 60 mM) or 9,11-dideoxy-11alpha,9alpha-epoxymethano prostaglandin F2alpha (U46619, 10(-7) M). Mechanical endothelial cell removal, blockade of K+ channels, muscarinic receptors or adrenoceptors did not influence the inhibitory effect of (-)-stepholidine on the contractile response evoked with noradrenaline in the segments. (-)-Stepholidine caused rightward shifts of the concentration-response curves for noradrenaline and phenylephrine. The pA2 values for (-)-stepholidine were 6.05 and 5.94 against noradrenaline and phenylephrine, respectively. Electrical field stimulation induced prazosin-sensitive frequency-dependent contractions in mesenteric small arteries. These contractions were significantly inhibited by 10(-6) and 10(-5) M (-)-stepholidine. In membranes from the rat cerebral cortex labelled with [3H]prazosin, (-)-stepholidine (10(-7)-10(-4) M) completely inhibited the specific binding of the ligand with a pKi of 5.6. The present investigation suggests the inhibitory effect of (-)-stepholidine on the alpha1-adrenoceptor-mediated contractions induced by exogenously added and nerve released noradrenaline in peripheral small arteries might contribute to a hypotensive effect of the drug. PMID- 9988104 TI - Hemodynamic actions of systemically injected pituitary adenylate cyclase activating polypeptide-27 in the rat. AB - The aims of this study were (1) to characterize the hemodynamic mechanisms underlying the hypotensive effects of pituitary adenylate cyclase activating polypeptide-27 (PACAP-27 0.1-2.0 nmol/kg, i.v.) in pentobarbital-anesthetized rats, and (2) to determine the roles of the autonomic nervous system, adrenal catecholamines and endothelium-derived nitric oxide (NO) in the expression of PACAP-27-mediated effects on hemodynamic function. PACAP-27 produced dose dependent decreases in mean arterial blood pressure and hindquarter and mesenteric vascular resistances in saline-treated rats. PACAP-27 also produced pronounced falls in mean arterial blood pressure in rats treated with the ganglion blocker, chlorisondamine (5 mg/kg, i.v.). The hypotensive and vasodilator actions of PACAP-27 were not attenuated by the beta-adrenoceptor antagonist, propranolol (1 mg/kg, i.v.), or the NO synthase inhibitor, N(G)-nitro L-arginine methyl ester (L-NAME 50 micromol/kg, i.v.). PACAP-27 produced dose dependent increases in heart rate whereas the hypotensive response produced by the nitrovasodilator, sodium nitroprusside (10 microg/kg, i.v.), was associated with a minimal tachycardia. The PACAP-27-induced tachycardia was unaffected by chlorisondamine, but was virtually abolished by propranolol. These results suggest that the vasodilator effects of PACAP-27 are due to actions in the microcirculation rather than to the release of adrenal catecholamines and that this vasodilation may not involve the release of endothelium-derived NO. These results also suggest that PACAP-27 produces tachycardia by directly releasing norepinephrine from cardiac sympathetic nerve terminals rather than by direct or baroreceptor reflex-mediated increases in sympathetic nerve activity. PMID- 9988105 TI - Effects of nitric oxide synthase inhibition on sympathetically-mediated tachycardia. AB - The aim of the present study was to determine whether inhibition of nitric oxide (NO) synthesis directly alters the tachycardia produced by sympathetically derived norepinephrine. The NO synthase inhibitor, N(G)-nitro-L-arginine methyl ester (L-NAME; 50 micromol/kg, i.v.), produced a marked rise in mean arterial blood pressure. This pressor response was associated with a fall in heart rate which involved the withdrawal of cardiac sympathetic nerve activity. The NO donor, sodium nitroprusside (5 microg/kg, i.v.), produced a pronounced fall in mean arterial blood pressure but only a minor increase in heart rate. The beta adrenoceptor agonist, isoproterenol (0.5 micromol/kg, i.v.), and the membrane permeable cAMP analogue, 8-(4-chlorophenylthiol)-cAMP (10 micromol/kg, i.v.), produced falls in mean arterial blood pressure and pronounced increases in heart rate. The indirectly acting sympathomimetic agent, tyramine (0.5 mg/kg, i.v.), produced a pressor response and a tachycardia. The effects of sodium nitroprusside, tyramine, isoproterenol and 8-(4-chlorophenylthiol)-cAMP on mean arterial blood pressure were not markedly affected by L-NAME. However, the tachycardia produced by these agents was considerably exaggerated in the presence of this NO synthesis inhibitor. These findings suggest that L-NAME potentiates the tachycardia produced by sympathetically-derived norepinephrine. The increased responsiveness to norepinephrine may involve (i) a rapid up-regulation of cardiac beta1-adrenoceptors and cAMP signaling in cardiac pacemaker cells due to the loss of the inhibitory influence of cardiac NO, and (ii) the up-regulation of beta1 adrenoceptor-mediated signal transduction processes in response to the L-NAME induced withdrawal of cardiac sympathetic nerve activity. PMID- 9988106 TI - Cardiovascular effects of captopril and enalapril in obese Zucker rats. AB - The effects of two weeks of oral administration of the angiotensin-converting enzyme inhibitors captopril (a sulphydryl-containing drug) and enalapril (which lacks the sulphydryl group) on skeletal muscle glucose uptake, arterial blood pressure, cardiac hypertrophy, proteinuria and aortic vascular reactivity in obese Zucker rats were evaluated. Captopril (50 mg kg(-1) once daily) and enalapril (10 mg kg(-1) did not modify body weight gain or food or water intake. Both drugs decreased systolic blood pressure (157+/-6, 133+/-4 and 136+/-3 mm Hg, in vehicle-, captopril- and enalapril-treated rats, respectively), blood glucose (172+/-8 vs. 151+/-7 and 158+/-5 mg dl(-1), respectively), proteinuria (46+/-10 vs. 17+/-2 and 18+/-2.5 mg dl(-1), respectively) and heart weight (2.17+/-0.03, 1.98+/-0.02 and 1.99+/-0.04 mg g(-1)of body weight, respectively). Plasma insulin concentration was significantly increased by enalapril (17+/-2 ng ml(-1) vs. 9+/ 2) but not by captopril (12+/-1). In the absence of insulin, the diaphragms from captopril- or enalapril-treated rats showed a significantly higher glucose uptake than that of controls (31% and 30% vs. control group, respectively). The presence of insulin in the incubation medium did not stimulate peripheral glucose uptake in the control group but significantly increased glucose uptake in diaphragms from captopril- or enalapril-treated rats (enhancement of glucose uptake vs. control: 52% and 43%, respectively). Endothelium-intact aortic rings from control Zucker rats showed a poor relaxant response to acetylcholine (maximal relaxation of 38.4+/-4.7%). Captopril significantly improved the endothelium-dependent vascular relaxation responses to acetylcholine and the endothelium-independent relaxation to the nitric oxide donor sodium nitroprusside whereas enalapril did not modify these relaxant responses. Neither captopril nor enalapril significantly affected the vascular contractile responses to the vasoconstrictors noradrenaline or KCl. In conclusion, the angiotensin-converting enzyme inhibitors captopril and enalapril reversed insulin resistance and the associated cardiovascular complications (cardiac hypertrophy, hypertension and proteinuria) in the obese Zucker rat, an animal model of non-insulin-dependent (type II) diabetes mellitus. However, only captopril, but not enalapril, improved the impaired endothelium-dependent and independent relaxant responses in the isolated rat aorta. PMID- 9988107 TI - Ischemia/reperfusion-induced arrhythmias in anaesthetized rats: a role of Na+ and Ca2+ influx. AB - We hypothesized that by limiting the Na+ and Ca2+ loading by a blocker/inhibitor of the Na+ channel (lidocaine), Na+ overload (R56865: N-[1-[4-(4 fluorophenoxy)butyl]-4-piperidinyl]-N-methyl-2-benzothiazo lamine), Ca2+ channel (verapamil), Na+ -H+ exchange (ethylisobutyl amiloride) or of Na+ -Ca2+ exchange (No. 7943: 2-[2-[4-(4-nitrobenzyloxy)phenyl]ethyl]isothiourea methanesulfonate), it should be possible to reduce ischemia/reperfusion-induced arrhythmias. To test this hypothesis, we used anaesthetized rats subjected to 5 min of coronary artery occlusion followed by 10 min of reperfusion to study antiarrhythmic effects of above compounds on reperfusion-induced ventricular premature beats, ventricular tachycardia, and reversible and irreversible ventricular fibrillation. Compound or saline was administered as an intravenous bolus injection at 5 min before ischemia. Pretreatment with lidocaine (5 mg/kg), verapamil (0.63 mg/kg), R56865 (0.63 mg/kg) or ethylisobutyl amiloride (1.25 mg/kg) significantly reduced or abolished all types of ventricular arrhythmias. However, pretreatment with verapamil was associated with second or third degree heart block in 3 out of 12 animals. Pretreatment with No. 7943 did not significantly influence the ischemia/reperfusion-induced ventricular arrhythmias. The present results suggest that both intracellular Na+ -and Ca2+ -loading play important roles in reperfusion-induced ventricular arrhythmias and the inhibition of Na+ -Ca2+ exchange to limit Ca2+ loading probably does not play any important role in ischemia/reperfusion-induced arrhythmias in anaesthetized rats. PMID- 9988108 TI - Comparison of the vascular relaxant effects of ATP-dependent K+ channel openers on aorta and pulmonary artery isolated from spontaneously hypertensive and Wistar Kyoto rats. AB - The vasorelaxant actions of adenosine 5'-triphosphate (ATP)-dependent K+ channel openers and sodium nitroprusside in isolated thoracic aorta and pulmonary artery of spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) rats (14-18 weeks old) were investigated. Cumulative addition of sodium nitroprusside and different ATP-dependent K+ channel openers (pinacidil, cromakalim, nicorandil, 2-(2"(1",3"-dioxolone)-2-methyl-4-(2'-oxo-1'-pyrrolidinyl)-6-nitro 2H-1-benzopyren (KR-30450) and aprikalim) to these preparations caused a concentration-dependent relaxation of noradrenaline-pre-contracted aorta and pulmonary artery from both strains. The relative order of relaxation potency, estimated by comparing the IC50, was sodium nitroprusside > KR-30450 > aprikalim > or = cromakalim > pinacidil > nicorandil in pulmonary artery and aorta from both strains. At high concentrations (> or =1 microM), cromakalim, aprikalim and KR-30450 produced a greater percentage relaxation in SHR aorta than in WKY aorta. However, there was no apparent difference between SHR and WKY in the relaxation response to all drugs tested on the pulmonary artery. The effects of cromakalim, aprikalim, pinacidil and KR-30450 observed in aorta and pulmonary artery were significantly attenuated by 3 microM glibenclamide. 6-Anilino-5,8 quinolinequinone (LY 83583, 1 microM), a soluble guanylate cyclase inhibitor, abolished the vasorelaxant effects of nicorandil and sodium nitroprusside. In conclusion, sodium nitroprusside and ATP-dependent K+ channel openers cause relaxation of noradrenaline-pre-contracted aorta and pulmonary artery from both strains. However, all the drugs tested failed to cause selective relaxation of the pulmonary artery relative to the thoracic aorta. PMID- 9988109 TI - Inhibition of nuclear factor-kappaB prevents the loss of vascular tone in lipopolysaccharide-treated rats. AB - We studied the role of nuclear factor-kappaB (NF-kappaB) on the tone and on the expression of inducible nitric oxide (NO) synthase, both evaluated in aortas from lipopolysaccharide-treated rats. Thoracic aorta rings from lipopolysaccharide treated rats (4 mg/kg, i.p.), compared to those from naive animals, showed: (i) reduced contractility to phenylephrine, (ii) progressive loss in tone when contracted with phenylephrine, (iii) increased inducible NO synthase protein expression and NF-kappaB activation. Pyrrolidine dithiocarbamate (10, 30, 100 mg/kg, i.p.), an antioxidant inhibitor of NF-kappaB activation, dose dependently suppressed all these lipopolysaccharide-induced effects. These results demonstrate that in vivo inhibition of NF-kappaB activation prevented the lipopolysaccharide-induced loss of vascular tone, an effect which was correlated to reduced expression of inducible NO synthase protein. PMID- 9988110 TI - Anti-inflammatory and analgesic effects of a novel pyrazole derivative, FR140423. AB - The pharmacological profile of a novel and newly discovered non-steroidal anti inflammatory and analgesic compound, 3-(difluoromethyl)-1-(4-methoxyphenyl)-5-[4 (methylsulfinyl)phenyl]pyraz ole (FR140423), was investigated. In recombinant human cyclooxygenase enzyme assays, the inhibition of prostaglandin E2 formation by FR140423 was 150 times more selective for cyclooxygenase-2 than cyclooxygenase 1. Oral administration of FR140423 dose dependently reduced carrageenin-induced paw edema and adjuvant arthritis. These effects were two- to three-fold more potent than those of indomethacin. Unlike indomethacin, FR140423 did not induce mucosal lesions in the stomach. FR140423 showed dose-dependent anti-hyperalgesic effects in the yeast-induced hyperalgesic model. This effect was five-fold more potent than that of indomethacin. Furthermore, FR140423 increased the pain threshold in non-inflamed paws and, unlike indomethacin, it produced an analgesic effect in the tail-flick test. These analgesic effects were blocked by the mu opioid antagonist naloxone. These results suggest that FR140423, a selective cyclooxygenase-2 inhibitor, is a potent non-steroidal anti-inflammatory drug (NSAID) without gastrointestinal side effects and is a unique compound having morphine-like analgesic effects. PMID- 9988111 TI - Activation of particulate guanylyl cyclase by Vibrio vulnificus hemolysin. AB - Recently we reported that Vibrio vulnificus hemolysin, an exotoxin produced by V. vulnificus, dilates rat thoracic aorta via elevated cGMP levels without affecting nitric oxide synthase. We investigated the mechanism further by observing the guanylyl cyclase activities in cytosolic, membrane, unfractionated, or reconstituted preparations. Hemolysin did not activate guanylyl cyclase in the membrane or cytosolic fraction, while it activated guanylyl cyclase in unfractionated or reconstituted preparation. The increased activity was not inhibited by the HS-142-1, a microbial polysaccharide which antagonizes atrial natriuretic peptide receptor, or 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ), a soluble guanylyl cyclase inhibitor. However, it was attenuated by 6 (phenylamino)-5,8-quinolinedione (LY 83.583), which inhibits the catalytic domain of both guanylyl cyclases, and by cholesterol, which blocks hemolysin incorporation into the membrane. Removing ATP, a cofactor of particulate guanylyl cyclase, attenuated the activation and ATPgammaS, a non-phosphorylating analog, restored it. These results suggest that V. vulnificus hemolysin activates particulate guanylyl cyclase via hemolysin incorporation into the vascular smooth muscle cell membrane in cooperation with certain unidentified cytosolic component(s). PMID- 9988113 TI - Cloning, expression and functional role of a nociceptin/orphanin FQ receptor in the porcine gastrointestinal tract. AB - The heptadecapeptide nociceptin/orphanin FQ is the cognate ligand for the opioid receptor-like orphanin FQ (OFQ) receptor, a member of the G protein-coupled receptor superfamily. The gastrointestinal tract is a major site of opioid action, and preliminary evidence suggests that an OFQ receptor may be expressed in rat small intestine. We addressed the hypothesis that this receptor is expressed in the gastrointestinal tract of the pig, a model for the human digestive system. A 1205-bp cDNA was isolated from porcine forebrain which contained the 370 amino acid open reading frame encoding the OFQ receptor. The receptor mRNA is likely to arise from a single gene, as determined by Southern blotting of porcine genomic DNA restriction digests using a porcine OFQ receptor cDNA probe. A semi-nested reverse transcriptase-polymerase chain reaction survey of receptor mRNA indicates that it is expressed in the porcine cerebral cortex and kidney, and along the length of the gastrointestinal tract. OFQ decreased initial contractile responses of porcine ileal smooth muscle strips to trains of electrical field stimulation with an IC50 value of 1.3 nM; its effects were resistant to the opioid antagonist, naloxone. The peptide, at concentrations > or =3 nM, also attenuated Isc elevations evoked by electrical transmural stimulation of mucosa-submucosa sheets from porcine ileum. The actions of OFQ appeared to differ from those previously reported for opioid receptor agonists in these tissue preparations. These results indicate that an OFQ receptor is expressed in the porcine intestine which modulates the neural control of intestinal smooth muscle contractility and mucosal transport. PMID- 9988112 TI - Expression of leptin receptor in lung: leptin as a growth factor. AB - Leptin receptors are expressed in various tissues in rodents but their function is not clear. The present studies were undertaken to investigate the function of the leptin receptor in mouse and human lungs. Cell proliferation, assessed with [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide] (MTT), was significantly less in primary cultures of tracheal epithelial cells of db/db mice than in those of their lean littermates. Mouse recombinant leptin significantly increased cell proliferation only in lean mice, but not in db/db mice. Reverse transcription-polymerase chain reaction (RT-PCR) study demonstrated the existence of a long form, OB-Rb type leptin receptor in both human lung tissue and lung squamous cell line (SQ-5). Cell proliferation, assessed with MTT, was dose dependently increased in SQ-5 cells incubated with 10-1000 ng/ml human recombinant leptin for 6 h. The 5-bromo-2'-deoxyuridine (BrdU) uptake into SQ-5 cells was also increased by the addition of 10-100 ng/ml human recombinant leptin. Mitogen-activated protein (MAP) kinase activity was significantly increased by 10 and 100 ng/ml human recombinant leptin in SQ-5 cells. MAP kinase kinase (MEK)-1-specific inhibitor, (2-[2-amino-3-methoxyphenyl]-4H-1-benzopyran-4 one) (PD98059), blocked the increase in BrdU uptake into SQ-5 cells caused by human recombinant leptin. In conclusion, leptin (OB-Rb) receptors exist in human lung tissue and leptin may have stimulatory effects on the proliferation of cells of a human cell line and mouse tracheal epithelial cells through its specific leptin receptor. PMID- 9988114 TI - Glibenclamide-sensitive K+ channels underlying levcromakalim-induced relaxation in pig urethra. AB - To investigate the possible mechanisms involved in the stable and long-lasting levcromakalim-induced relaxation of the resting urethral tone, we have performed mechanical and voltage-clamp experiments using intact tissue and isolated cells from pig urethra, respectively. At negative membrane potentials, levcromakalim induced time- and voltage-independent membrane currents in whole-cell configurations. In cell-attached patches, levcromakalim not only increased the open-state probability (the NP(0) value) of the glibenclamide-sensitive 43 pS K+ channel (K(GS)) in a concentration-dependent manner, but also activated K(GS) with a time- and voltage-independence. During long burst-like channel activity, neither the mean open lifetime nor the mean closed time of K(GS) exhibited voltage-dependency between -100 and - 40 mV. It is concluded that levcromakalim causes a stable and potent relaxation of pig urethra through opening of K(GS) which possesses time- and voltage-independent activating mechanisms. PMID- 9988115 TI - Gemcitabine cytotoxicity of human malignant glioma cells: modulation by antioxidants, BCL-2 and dexamethasone. AB - Gemcitabine is a novel antimetabolite drug that acts by multiple mechanisms, including inhibition of ribonucleoside diphosphate reductase, of dCMP deaminase and of dCTP incorporation into DNA and RNA. Here, we report that gemcitabine induces cytotoxic and clonogenic death of 12 human malignant glioma cell lines at clinically relevant concentrations around 1 microM. Gemcitabine is thus approximately 100-fold more active than the congener drug, cytarabine. Gemcitabine cytotoxicity of glioma cells does not require wild-type p53 activity: (i) there was no difference in the susceptibility to gemcitabine between cell lines with wild-type p53 and cell lines with mutant or deleted p53; (ii) ectopic expression of a temperature-sensitive p53 protein either at wild-type (32.5 degrees C) or at mutant (38.5 degrees C) conformation had no significant influence on gemcitabine-induced cell death. Gemcitabine cytotoxicity was unaffected by the antioxidants, N-acetylcysteine and phenyl-N-tert-butyl-alpha phenylnitrone. There was no correlation between the susceptibility to gemcitabine and the endogenous expression of the B cell lymphoma-2 (BCL-2)-family proteins BCL-2, BCL-XL, myeloid cell leukemia-1 (MCL-1), BCL-2-associated X protein (BAX), BCL-2 homologous antagonist/killer (BAK) and BCL-XS. Ectopic expression of BCL-2 moderately attenuated gemcitabine-induced cell death. Similarly, preexposure to the synthetic steroid, dexamethasone, which is commonly used to control cerebral edema in brain tumor patients, reduced gemcitabine cytotoxicity. We conclude that the clinical evaluation of gemcitabine for the adjuvant chemotherapy of malignant glioma is warranted. PMID- 9988116 TI - Pyrazolopyridine derivatives act as competitive antagonists of brain adenosine A1 receptors: [35S]GTPgammaS binding studies. AB - The effects of adenosine receptor ligands and three novel pyrazolopyridine derivatives on guanosine-5'-O-(3-[35S]thio)triphosphate ([35S]GTPgammaS) binding to rat cerebral cortical membranes were examined. [35S]GTPgammaS binding was stimulated in a concentration dependent manner by several adenosine receptor agonists. The adenosine A2a receptor selective agonist, 2-p-(2 carboxyethyl)phenethylamino-5'-N-ethylcarboxamidoadenosine (CGS 21680), was ineffective confirming specificity for adenosine A1 receptor activation. 2-Chloro N6-cyclopentyladenosine (CCPA; 10(-7) M)-stimulated [35S]GTPgammaS binding was inhibited by xanthine and pyrazolopyridine based adenosine receptor antagonists. The concentration-response curve for CCPA-stimulated [35S]GTPgammaS binding was shifted to the right with increasing concentrations of antagonist without significant changes in maximal response. Schild analyses determined pK(B) values of 8.97, 8.88, 8.21, 8.16, 7.79 and 7.65 for 8-cyclopentyl-1,3-dipropylxanthine (DPCPX), (R)-1-[(E)-3-(2-phenylpyrazolo[1,5a]pyridin-3-yl) acryloyl]-2-piperidine ethanol (FK453), 6-oxo-3-(2-phenylpyrazolo[1,5a]pyridin-3-yl)-1(6H) pyridazinebutyric+ ++ acid (FK838), 9-chloro-2-(2-furyl)[1,2,4]triazolo [1,5c]quinazolin-5-amine (CGS 15943), 8-cyclopentyl-1,3-methylxanthine (CPT) and (R)-1-[(E)-3-(2-phenylpyrazolo[1,5a]pyridin-3-yl) acryloyl]-piperidin-2-yl acetic acid (FK352), respectively. Schild slopes were close to unity, confirming that these novel pyrazolopyridine derivatives act as competitive antagonists at rat brain adenosine A1 receptors. PMID- 9988117 TI - Mitogen-activated protein kinase phosphatase: a negative regulator of the mitogen activated protein kinase cascade. AB - Mitogen-activated protein kinases (MAPKs) are activated by various stimuli, such as growth factors, cytokines, or stress, and are considered to be important mediators in intracellular signal transduction networks. The dual-specificity kinases, MAPK kinases (MKKs), which phosphorylate the TXY motif in the catalytic domain of MAPKs, can cause the activation of MAPKs. Recently, a family of dual specificity phosphatases has been identified, members of which are able to dephosphorylate and inactivate MAPKs. The studies cited in this review have revealed that these MAPK phosphatases might play an important role in various cellular functions by downregulating the MAPK cascade. PMID- 9988118 TI - Adenosine and cerebral ischemia: therapeutic future or death of a brave concept? AB - Numerous studies have consistently shown that agonist stimulation of adenosine A1 receptors results in a significant reduction of morbidity and mortality associated with global and focal brain ischemia in animals. Based on these observations, several authors have suggested utilization of adenosine A1 receptors as targets for the development of clinically viable drugs against ischemic brain disorders. Recent advent of adenosine A1 receptor agonists characterized by lowered cardiovascular effects added additional strength to this argument. On the other hand, although cardioprotective, adenosine A3 receptor agonists proved severely cerebrodestructive when administered prior to global ischemia in gerbils. Moreover, stimulation of adenosine A3 receptors appears to reduce the efficacy of some of the neuroprotective actions mediated by adenosine A receptors. The review discusses the possible role of adenosine receptor subtypes (A1, A2, and A3) in the context of their involvement in the pathology of cerebral ischemia, and analyzes putative strategies for the development of clinically useful strategies based on adenosine and its receptors. It also stresses the need for further experimental studies before definitive conclusions on the usefulness of the adenosine concept in the treatment of brain ischemia can be made. PMID- 9988119 TI - Treatment with a polyunsaturated fatty acid prevents deleterious effects of Ro4 1284. AB - Ro4-1284 (2-Ethyl-1,3,4,6,7,11b-hexahydro-3-isobutyl-9,10-dimethoxy-2H-benzo[a] quinolizin-2-ol hydrochloride), a benzoquinolizine, is a potent dopamine depletion agent whose acute and chronic administration results in a (1) deterioration of learning in the Morris Water Maze and passive avoidance tasks, (2) decrease in locomotion and rearing, (3) intense hypothermia, and (4) decrease in the percentage of polyunsaturated fatty acids and an increase in the level of cholesterol in neuronal membranes. Pretreatment with a specific mixture of free polyunsaturated fatty acids prevents most of the behavioral, physiological, and biochemical effects of Ro4-1284 except for rearing. We propose that the dopamine mediated functions tested in this study are dependent on the interaction of intact dopamine D1 and D2 receptors. Rearing, which is controlled only by dopamine D1 receptors, remained, therefore, unaffected. Our hypothesis is that SR 3 exerts its beneficial effects by normalizing the structure and function of the neuronal membrane and by restoring dopamine D2 receptor functions. PMID- 9988120 TI - Novel sigma receptor ligands attenuate the locomotor stimulatory effects of cocaine. AB - Cocaine interacts with sigma receptors, suggesting that these sites are important for many of its behavioral effects. Therefore, two novel sigma receptor ligands, BD1008 (N-[2-(3,4-dichlorophenyl)ethyl]-N-methyl-2-(1-pyrrolidinyl)ethylamine) and BD1063 (1-[2-(3,4-dichlorophenyl)ethyl]-4-methylpiperazine), were evaluated for their ability to attenuate cocaine-induced locomotor activity. Receptor binding studies showed that BD1008 and BD1063 have nanomolar affinities for sigma1 and sigma2 sites, but a 250-fold or lower affinity for nine other receptors, making them among the most selective sigma receptor ligands identified. In behavioral studies, pretreatment of mice with BD1008 or BD1063 produced a two-fold increase in the ED50 for the locomotor stimulatory effects of cocaine. These results suggest that sigma receptors are involved in the behavioral effects of cocaine. PMID- 9988121 TI - Effect of alterations in extracellular norepinephrine on adrenoceptors: a microdialysis study in freely moving rats. AB - Chronic electroshock treatment (once daily for 12 days) increases extracellular norepinephrine in the frontal cortex and hippocampus as measured by microdialysis. This chronic treatment produced an elevation of basal norepinephrine overflow into extracellular space while both the first and the twelfth treatments produced a transient increase in norepinephrine overflow of about 40 min. Acutely, desmethylimipramine (10 mg/kg) treatment significantly increased extracellular norepinephrine. While chronic desmethylimipramine (once daily for 10 days) increased basal overflow of norepinephrine in the frontal cortex and hippocampus, the tenth daily administration of desmethylimipramine did not produce a statistically significant increase in extracellular norepinephrine. Both daily electroshock and daily desmethylimipramine produced down regulation of beta-adrenoceptors in the hippocampus and the frontal cortex. Chronic electroshock caused up regulation of alpha-adrenoceptors in the frontal cortex but not in the hippocampus while chronic desmethylimipramine administration did not alter alpha-adrenoceptors in either structure. Depletion of norepinephrine with reserpine or with 6-hydroxydopamine prevented the down regulation of beta adrenoceptors while depletion of this neurotransmitter did not prevent the electroshock-induced up regulation of alpha-adrenoceptors in the frontal cortex. These data suggest that down regulation of beta-adrenoceptors is mediated through increases in extracellular norepinephrine. In contrast, up regulation of alpha adrenoceptors appears to be independent of norepinephrine release and does not require the presence of noradrenergic neurons in order to be induced by electroshock. PMID- 9988122 TI - Region specific expression of NMDA receptor NR1 subunit mRNA in hypothalamus and pons following chronic morphine treatment. AB - The NMDA receptor has been implicated in opioid tolerance and physical dependence. Using in situ hybridization techniques, the effects of chronic morphine treatment on the expression of mRNAs encoding the NMDA receptor subunits NRI, NR2A, and NR2B were investigated. A significant increase in the level of the NR1 subunit mRNA was found in the locus coeruleus and the hypothalamic paraventricular nucleus following 3 days of intracerebroventricular (i.c.v.) morphine infusion (26 nmol microl(-1) h(-1)) through osmotic minipumps. No changes were detected in expression of the NRI mRNA in the frontal cortex, caudate-putamen, nucleus accumbens, amygdala, CA1, CA2, and the dentate gyrus of the hippocampus, and in the central grey after morphine treatment. The expression of NR2A and NR2B subunit mRNAs did not change after morphine treatment in any brain region. These results suggest that changes in gene expression of the NRI subunit of the NMDA receptor are involved in the development of morphine tolerance and dependence. PMID- 9988123 TI - (1S,3R)-ACPD, a metabotropic glutamate receptor agonist, enhances damage after global ischaemia. AB - There are opposing results in the literature concerning the influence of (1S,3R) ACPD [(1S,3R)-1-aminocyclopentane-1,3-dicarboxylate: group I/II metabotropic glutamate receptor agonist) on neurodegeneration, showing both enhancement and reduction of damage. We examined the effects of (1S,3R)-ACPD, given in various application schedules, on global ischaemia in gerbils. The most pronounced effect was a significant increase of hippocampal damage when the drug was applied at 20 mg/kg i.p. pre ischaemia. All other experiments with lower concentrations (0.02-2 mg/kg), other time schedules (post-ischaemic application) or co-application of a selective group I metabotropic glutamate receptor antagonist (4-CPG: (S)-4 carboxyphenylglycine), had no influence on neuronal density. PMID- 9988124 TI - Anaphylaxis increases 8-iso-prostaglandin F2alpha release from guinea-pig lung in vitro. AB - 8-Iso-prostaglandin F2alpha, release from isolated and perfused guinea-pig lung was measured by radioimmunoassay. 8-Iso-prostaglandin F2alpha release was detectable under basal conditions and increased 10-fold during antigen-induced bronchoconstriction, concomitant with the increase of thromboxane B2 and prostaglandin E2. The anti-8-iso-prostaglandin F2alpha serum used in the radioimmunoassay seems to be quite specific for this compound. Pretreatment of lungs with indomethacin (a non-selective inhibitor of cyclooxygenase) reduced 8 iso-prostaglandin F2alpha release under basal conditions and completely abolished the increase observed during lung anaphylaxis. Pretreatment of lungs with NS 398 (N-[2-cyclohexyl]-4-nitrophenyl methanesulphonamide), a selective inhibitor of cyclooxygenase-2, did not change basal or antigen-induced 8-iso-prostaglandin F2alpha release at all. We conclude that under basal conditions guinea-pig lung perfusates contain low levels of 8-iso-prostaglandin F2alpha-like immunoreactivity, which increase 10-fold during antigen-induced bronchoconstriction. This isoprostane seems to be derived from the cyclooxygenation of arachidonic acid via the constitutive form of cyclooxygenase. PMID- 9988125 TI - A soluble gradient of the neuropeptide secretoneurin promotes the transendothelial migration of monocytes in vitro. AB - Secretoneurin, derived from the chromogranin secretogranin II, triggers the selective migration of human monocytes, eosinophils, fibroblasts, endothelial and smooth muscle cells. More recently, we located specific binding sites on the human monocytic cell line MonoMac-6. Differentiated U937 transendothelial diapedesis was evaluated using an in vitro model of the vascular wall and specific monoclonal antibodies against CD11/CD18 and the alpha-chains of the very late activation antigen (VLA)-4 were used to evaluate involved adhesion molecules. Results showed a significant migratory response to secretoneurin between 10(-8) to 10(-10) M. Migration was comparable to a maximal effect induced by the monocyte chemotactic agent N-formyl-Met-Leu-Phe (fMLP, 10(-8) M). Rabbit anti-secretoneurin antibodies were able to block the neuropeptide effect but not of fMLP and a trypsinized secretoneurin preparation as well as the secretogranin II-fragment EL-17 were ineffective in eliciting migration. Transmigration of U937 across endothelial-layers toward secretoneurin is inhibited by antibodies to CD11/CD18 adhesion molecules. The novel neuropeptide secretoneurin may play a role in regulating migration of monocytes into the subendothelial space, supposing a role in inflammatory responses. PMID- 9988126 TI - Nonspecific effects of the pharmacological probes commonly used to analyze signal transduction in rabbit parietal cells. AB - In order to examine some possibly misleading conclusions of the pharmacological analysis of the signal transduction pathways of gastric acid secretion, we evaluated various agents including inhibitors of protein kinase C, cyclic AMP dependent protein kinase, phospholipase C, phospholipase A2, lipoxygenase, casein kinase, calmodulin, myosin light chain kinase, tyrosine kinase, anion exchanger, and protein phosphatase; and activators of protein kinase C. Among them, the cyclic AMP-dependent protein kinase inhibitor N-[2-(p-bromocinnamylamino)ethyl]-5 isoquinolinylsulfonamide (H-89), the phospholipase A2 inhibitor 2-(p amylcinnamoyl)amino-4-chlorobenzoic acid (ONO-RS-082), three myosin light chain kinase inhibitors (1-(5-iodonaphthalene-1-sulfonyl)-1H-hexahydro-1,4-diazepine (ML-7), 1-(5-chloronaphthalene-1-sulfonyl)-1H-hexahydro-1,4-diazepine (ML-9), and wortmannin), the anion exchanger inhibitor 4,4'-diisothiocyanatostilbene-2,2' disulfonic acid (DIDS), the phospholipase C inhibitor neomycin, and most known calmodulin antagonists strongly inhibited [14C]aminopyrine accumulation, an indicator of acid secretion, in isolated rabbit gastric glands stimulated by N6,2'-O-dibutyryl-cyclic AMP. ONO-RS-082, calmidazolium, and DIDS inhibited H+,K+ ATPase. Most of the chemicals with antisecretory activity showed protonophore like activity in gastric microsomes as well as in the mitochondria. It is concluded that H-89, ONO-RS-082, ML-7, ML-9, neomycin, and all calmodulin antagonists tested so far should not be used as tools to analyze gastric acid secretion. PMID- 9988127 TI - Complex formation of skeletal muscle Ca2+-regulatory membrane proteins by halothane. AB - In skeletal muscle, halothane affects the functions of several Ca2+-regulatory membrane proteins involved in the excitation-contraction-relaxation cycle. To investigate the mechanism by which this volatile anesthetic interferes with Ca2+ homeostasis, we studied potential changes in protein-protein interactions by halothane. Using comparative immunoblotting of microsomal muscle proteins separated on native and denaturing gels, we show here that halothane induces oligomerization of the terminal cisternae Ca2+-binding protein calsequestrin, the junctional ryanodine receptor Ca2+-release channel and the transverse-tubular alpha1-dihydropyridine receptor. This agrees with previous reports on the modulation of Ca2+-release activity by halothane since interactions between the voltage-sensing alpha1-dihydropyridine receptor, the ryanodine receptor and the luminal Ca2+-reservoir might result in a rapid release of Ca2+-ions. Furthermore, this study supports the idea that specific protein sites are involved in the action of inhalational anesthetics and that halothane might trigger abnormal Ca2+ homeostasis in malignant hyperthermia via oligomerization of the mutated ryanodine receptor. PMID- 9988128 TI - Local renin-angiotensin system and mitogen-activated protein kinase activation in rat aorta. AB - We previously reported that endogenous angiotensin II is released to cause mitogen-activated protein (MAP) kinase stimulation in the media portion of the vasculature. In this study, we examined whether a functional renin-angiotensin system is indeed present within the media of the vasculature. In rat aortic strips, endothelium removal produced an increase of MAP kinase activity. The MAP kinase activation was inhibited either by the renin inhibitor pepstatin A or by the angiotensin-converting enzyme inhibitor captopril. The degree of the inhibition of the MAP kinase activation by pepstatin A, captopril and the angiotensin receptor antagonist losartan was almost the same. Pepstatin A inhibited MAP kinase activation induced by renin but not by angiotensin I and angiotensin II. Captopril inhibited the MAP kinase activation induced by angiotensin I but not by angiotensin II. In nephrectomized rat aortic strips, endothelium removal also produced an increase in MAP kinase activity, but the MAP kinase activation was considerably small and minimally inhibited by losartan. Nephrectomy produced a marked decrease in plasma renin activity. These findings suggest that an apparently fully intact and functional renin-angiotensin system is present in the media of the rat vasculature and this system serves to increase MAP kinase activity. It appears that renin plays the determining role in the regulation of angiotensin generation also in the media and the major source of the renin is renin of kidney origin. PMID- 9988129 TI - Mechanism of rise and decay of 2,5-di-tert-butylhydroquinone-induced Ca2+ signals in Madin Darby canine kidney cells. AB - We examined the effect of 2,5-di-tert-butylhydroquinone (BHQ) on intracellular Ca2+ concentrations ([Ca2+]i) measured by fura-2 fluorimetry in Madin Darby canine kidney (MDCK) cells. BHQ increased [Ca2+]i in a dose-dependent manner with an EC50 of 40 microM. The Ca2+ signal showed a slow onset, a gradual decay and a sustained plateau in normal Ca2+ medium. Depletion of the endoplasmic reticulum Ca2+ store by incubation with 0.1 mM BHQ for 6 min abolished the [Ca2+]i increase evoked by bradykinin or ATP, suggesting that BHQ depleted the inositol 1,4,5 trisphosphate (IP3)-sensitive Ca2+ store. Removal of extracellular Ca2+ reduced the BHQ response by 50%. The Ca2+ signal was initiated by Ca2+ release from the internal store, followed by capacitative Ca2+ entry which was abolished by 100 microM La3+ or 50 microM Gd3+ and was partly inhibited by 1-[beta-[3-(4 methoxyphenyl)propoxy]-4-methoxyphenethyl]-1H-imidazole hydrochloride (SKF 96365). After depletion of the endoplasmic reticulum Ca2+ store, by incubation with another inhibitor of the endoplasmic reticulum Ca2+ pump, thapsigargin for 30 min, BHQ did not elevate [Ca2+]i, suggesting that the BHQ-induced Ca2+ influx was largely due to capacitative Ca2+ entry, and that BHQ released Ca2+ from the thapsigargin-sensitive endoplasmic reticulum store. We investigated the mechanism of decay of the BHQ response. Pretreatemt with La3+ (or Gd3+) or alkalization of the extracellular medium to pH 8 significantly potentiated the Ca2+ signal, whereas pretreatment with carbonylcyanide m-chlorophenylhydrazone (CCCP) or oligomycin, or removal of extracellular Na+, had no effect. Collectively, our results suggest that BHQ increased [Ca2+]i in MDCK cells by depleting the endoplasmic reticulum Ca2+ store followed by capacitative Ca2+ entry, with both pathways contributing equally. The decay of the BHQ response is effected by Ca2+ efflux via the plasma membrane Ca2+ pump, but not by efflux via Na+/Ca2+ exchange or sequestration by the mitochondria. PMID- 9988130 TI - Endothelin ET(A) receptor antagonist reverses the inhibitory effect of platelet derived growth factor on cytokine-induced nitric oxide production. AB - Cytokines and cytokine-induced nitric oxide (NO) play important roles in inflammatory glomerular diseases, and both platelet-derived growth factor and transforming growth factor-beta inhibit cytokine-induced NO production. In this study, we demonstrated that a selective endothelin ET(A) receptor antagonist, BQ 485 (Hexahydro-1H-azepinylcarbonyl-Leu-D-Trp-D-Trp-OH), reversed the inhibitory effect of platelet-derived growth factor on cytokine-induced NO production, but not that of transforming growth factor-beta. Our findings suggest a difference between the inhibitory mechanisms of platelet-derived growth factor and transforming growth factor-beta on cytokine-induced NO production. PMID- 9988131 TI - Altered ratio of endothelin ET(A)- and ET(B) receptor mRNA in bronchial biopsies from patients with asthma and chronic airway obstruction. AB - Using a reverse transcription-polymerase chain reaction (RT-PCR) based assay the ratio of mRNA for the human endothelin ET(A) and ET(B) receptors in bronchial biopsies was assessed. In patients with diagnoses like bronchial cancer, endothelin ET(A) mRNA was the dominating subtype (ratio 3.74 +/- 0.99). Subjects with the diagnosis of asthma or chronic obstructive pulmonary disease showed significantly higher levels (ratio 0.81 +/- 0.04) of endothelin ET(B) receptor mRNA compared to endothelin ET(A) receptor mRNA. Our results indicate alterations in the endothelin receptor balance in these states. PMID- 9988132 TI - MGMT- and P450 3A-inhibitors do not sensitize glioblastoma cell cultures against nitrosoureas. AB - AIM, MATERIAL AND METHODS: Using RT-PCR and immunohistochemistry the expression of cytochrome P450 was evaluated in a series of 22 glioblastomas and 4 anaplastic astrocytomas (WHO grade III). Since rat liver P450 can catalyze the denitrosation of the nitrosourea compound BCNU in vitro, cell culture experiments were performed to test a possible sensitizing effect of P450 3A inhibitors (tiamulin and ketoconazole) in BCNU treatment of glial tumor cells. O6-benzylguanine (BG), an inhibitor of the DNA repair enzyme O6-methylguanine-DNA-methyltransferase (MGMT), was used in parallel experiments, since MGMT is discussed as a main mechanism in nitrosourea resistance. RESULTS: RT-PCR reactions with primers designed according to the sequences for CYP1A1 and CYP2E1 were always positive, while those for CYP1A2 and CYP2D6 were negative. The strongest PCR products were detected with CYP3A primers, but CYP3A expression was heterogeneous within the tumor samples. Antibodies to human liver CYP3A4 stained a subfraction of tumor cells (18% of the cells in glioblastomas and 14% in grade III astrocytomas) and to some extend neurons in normal brain areas, while astrocytes were negative. For cell culture experiments with P450 3A and MGMT inhibitors, early passages of 3 glioblastomas, a late passage of an immortalized cell line derived from a reoccurring glioblastoma, and the human glioblastoma line LN405 were used. The sensitivity of the tumor cells for both nitrosourea compounds was very low, when low concentrations were applied (comparable to the achievable blood concentrations in glioma patients). Strong effects did only occur when the concentrations were raised 9-fold or 27-fold. CONCLUSION: In no case could a significant sensitizing effect of P450 3A- and MGMT inhibitors be demonstrated. PMID- 9988133 TI - Parahippocampal pathology in Creutzfeldt-Jakob disease. AB - BACKGROUND: The hippocampal lesions in Creutzfeldt-Jakob disease (CJD) have been reported to be characteristically mild, but it has not been well known how the lesions change pathologically from the entorhinal cortex to the hippocampus. MATERIAL AND METHODS: This study was designed to clarify the ambiguity attending the parahippocampal lesions in CJD. Fourteen cases with pathologically diagnosed CJD were studied. They were classified into 2 groups: group I, which did not have cortical status spongiosus (SS) and included 5 cases; and group II, which had cortical SS and included 9 cases. Neuronal loss, astrocytosis, and spongiform change were studied in lesions in the entorhinal cortex, parasubiculum, presubiculum (external and internal principal laminae), subiculum, and prosubiculum, respectively. RESULTS: The results of this study showed that in group I neuronal loss and astrocytosis were more severe in the parasubiculum and the external principal lamina of the presubiculum than in the other regions including the entorhinal cortex, and in group II the lesions in the entorhinal cortex, parasubiculum, and the external principal lamina of the presubiculum were more severe than in the other regions. In both groups in this study the lesions from the internal principal lamina of the presubiculum through the prosubiculum in the direction of the hippocampus were mild, which could be the least vulnerable in the parahippocampal gyrus in CJD. CONCLUSION: On the contrary, our findings also raise the possibility that the parasubiculum and the external principal lamina of the presubiculum may be the structures most vulnerable to early lesions in the parahippocampal gyrus in CJD. To know the pathogenesis of these lesions may be the clue to delineate the mechanisms by which the neurons could be spared. PMID- 9988134 TI - Neural expression profile of Elav-like genes in human brain. AB - BACKGROUND: Hel-N1 and HuD belong to the elav gene family and have a considerable role in neuronal development. However, there is only limited information available on the expression profile in human brain and neural tumor cell lines. METHOD: Therefore, RT-PCR analysis has been performed on human fetal, normal adult, and psychiatric brains (from patients with schizophrenia, Alzheimer's disease, and alcoholism) as well as 20 glioblastoma and 9 medulloblastoma cell lines. RESULTS: Both, Hel-N1 and HuD were abundantly expressed in all brain samples with no obvious difference. However, the neural tumor cell lines showed a differential expression pattern. The medulloblastoma cell lines expressed at least one of the genes in a frequency of 67% for HuD and 78% for Hel-N1 transcripts, respectively. In contrast to the glioblastoma cell lines, which revealed no evidence for HuD RT-PCR products. Surprisingly, 55% of the glioblastoma cell lines showed Hel-N1 expression. CONCLUSION: These observations indicate that Hel-N1 and HuD participate in molecular processes in human brain, both during development and in the mature adult brain. Hel-N1 and HuD transcriptional activity are stable markers for medulloblastoma cell lines, a tumor, which is thought to be derived from a neuronal precursor cell. The role of Hel-N1 in glioblastomas, the most prominent representative of the glial tumors is presently unclear. This finding is the first indication for a possible involvement of an Elav-like gene product in the glial cell lineage. PMID- 9988135 TI - Critically ill patients: immunological evidence of inflammation in muscle biopsy. AB - AIM AND METHOD: To verify whether muscle necrosis in critically ill patients could be due to an inflammatory process, we tested muscle biopsies from five intensive care patients with different inflammation-specific immunocytochemical markers (antibodies anti-class I major histocompatibility complex products (class I MHCP or HLA I), membrane attack complex (MAC), T lymphocytes helper-inducer (CD4), cytotoxic (CD8) and pan-B-lymphocytes). RESULTS: In three patients muscle biopsy showed class I MHCP positivity on the surface membrane of several groups of fibres, mainly perifascicular, and scattered microvascular deposits of MAC. In the other two patients muscle biopsy did not show class I MHCP and MAC positivity. CONCLUSION: Our results suggest that inflammation may be a component of muscle damage in some critically ill patients. PMID- 9988136 TI - Cerebrospinal fluid filtration and immunoglobulins in multifocal motor neuropathy. AB - Cerebrospinal fluid (CSF) filtration has been shown to be of benefit in chronic inflammatory, demyelinating polyneuropathy, but has not been applied to multifocal motor neuropathy (MMN) so far. Twenty-seven months after a 48-year-old male patient had developed slowly progressive, distally prominent monoparesis of the left arm, MMN was diagnosed. Conduction blocks were found in the left brachial plexus after median, ulnar, and radial nerve stimulation. Serum anti-GM1 antibody titers were markedly increased. Biopsy of the motor long thoracic nerve showed reduction of small caliber myelinated axons and irregularly shaped myelin lamellae. Treatment with immunoglobulins 29, 31, 36, and 39 months after onset was followed by a distinct improvement each time. Thirty-four months after onset, one liter CSF was filtered off by means of a bidirectional syringe pump with only minor therapeutic effect. In conclusion, immunoglobulins had a stronger therapeutic effect than CSF filtration on the MMN patient described. PMID- 9988137 TI - A chondromyxoid fibroma-like tumor of the cranial convexity: immunohistochemical and ultrastructural study. AB - A rare chondromyxoid fibroma-like tumor arising from the temporal bone in a 49 year-old man is described. This case appears to be only the second reported of a cranial lesion of the tumor for which diagnosis could be confirmed by immunohistochemistry and electron microscopy. PMID- 9988139 TI - Amygdalo-subicular degeneration in a young adult with status epilepticus and choreoathetoid movements of acute onset. AB - Selective amygdalo-subicular degeneration was observed in a 25-year-old woman with encephalopathy of unknown etiology. Following flu-like symptoms, the patient presented with confusion and generalized seizures. Subsequently, she developed persistent stupor with absence of the brainstem reflexes, refractory status epilepticus accompanied by hyperthermia, and exhibited choreoathetoid movements. Despite therapies her condition showed no improvement, and she died four months after the onset of disease. Postmortem examinations revealed no evidence suggestive of viral encephalitis, and instead distinctive bilateral lesions were seen in the subiculum (the subiculum proper and the prosubiculum) and the basolateral nuclear group of the amygdala. The hippocampus proper from CA1 to dentate fascia was unremarkable. The selective amygdalo-subicular degeneration, for which pathogenesis remained unknown, was inconsistent with her serious clinical condition. To our knowledge, similar pathology has not been described so far. PMID- 9988138 TI - Multiple intracerebral metastases of a 17-year-old girl with previously diagnosed neurofibromatosis type I. AB - We report a case of a 17-year-old girl with multiple intracerebral tumors. Previously, a neurofibroma in the posterior mediastinum and neurofibromatosis had been diagnosed. She developed a spastic tetraparesis with a prominent hemiparesis of the right side within several weeks. On admission we found clinical signs of elevated intracranial pressure. Cranial CT and MRI scans showed multiple space occupying intracerebral tumors, thought to be multiple meningeoma. The patient was referred to the neurosurgical department, where two of the intracerebral tumors were excised. The histological examination revealed metastases of a neurosarcoma. PMID- 9988140 TI - Does early anemia correction prevent complications of chronic renal failure? AB - Anemia is a common complication of chronic renal failure (CRF). With the availability of recombinant human erythropoietin (rhEPO) over the last decade, much progress has been made in the management of anemia in patients with end stage renal disease (ESRD) [Eschbach 1995, Gimenez and Scheel 1994, Muirhead et al. 1995, Winearls 1995]. The clearest benefit of rhEPO in ESRD is a substantial reduction in transfusion dependency, which reduces the need for hospital admission and the risk of viral transmission. Improvements in hemostasis and a decrease in human leucocyte antigen (HLA) antibodies have also been reported. Beneficial effects of rhEPO on the cardiovascular system in ESRD include regression of left ventricular hypertrophy (LVH), improvement of angina, and a modest increase in aerobic work capacity. Treatment of anemia with rhEPO has also been shown to improve cognitive function, socialization and quality of life in dialysis patients, although this has not led to better vocational rehabilitation or employment status. It has also been reported that a lower hemoglobin (Hb) content is an independent risk factor for increased mortality in hemodialysis patients [Harnett et al. 1995]. Clearly, therefore, treatment of anemia associated with ESRD is required and beneficial. The optimum treatment of anemia prior to dialysis, however, is still a matter for debate. PMID- 9988141 TI - Increased endothelial nitric oxide synthase mRNA level in Bartter's and Gitelman's syndrome. Relationship to vascular reactivity. AB - AIM: Patients with Bartter's syndrome and Gitelman's syndrome have reduced vascular reactivity, normo-hypotension and decreased peripheral resistances in spite of biochemical and hormonal abnormalities typical of hypertension. Since we found that both types of patients have increased urinary NO2-/NO3-, metabolites of NO, that correlated with their increased urinary cGMP, second messenger of NO, we examined the possible role of NO system in the pathophysiology of these syndromes. PATIENTS AND METHODS: We used a molecular biologic approach and studied ecNOS gene expression by PCR-amplification of cDNA obtained by RT-PCR of RNA extracted by patients and healthy controls monocytes. RESULTS: ecNOS is overexpressed in monocytes from patients with Bartter's and Gitelman's syndrome relative to controls: - 0.306 +/- 0.012 Densitometric Units (0.313 +/- 0.006, N = 3 for Bartter's patients; 0.302 +/- 0.009, N = 5 for Gitelman's patients) vs. 0.192 +/- 0.018, p < 0.0001. CONCLUSION: This overexperession presumably accounts for their increased NO production; thus it could be likely that elevated ecNOS and NO levels are a part of pathophysiological process(es) that leads to their characteristic reduced vascular responses. However, the relationship between the alterations in the NO signalling system observed in this study and the mutations in either Na+-K+-2Cl cotransporter or in a K+ channel ROMK or in Cl- channel ClCNKB in Bartter's syndrome and in Na+-Cl- cotranstransporter in Gitelman's syndrome, recently reported as their primary defects remains to be defined. PMID- 9988142 TI - A randomized trial of sevelamer hydrochloride (RenaGel) with and without supplemental calcium. Strategies for the control of hyperphosphatemia and hyperparathyroidism in hemodialysis patients. AB - OBJECTIVE: We have previously shown sevelamer hydrochloride (RenaGel) to be an effective and well-tolerated treatment for hyperphosphatemia in hemodialysis patients. PATIENTS AND METHODS: We performed a randomized clinical trial to compare the efficacy of RenaGel alone and RenaGel with calcium, using the serum phosphorus concentration and intact parathyroid hormone (PTH) as the principal outcomes of interest. Calcium (900 mg elemental) was provided as a once-nightly dose on an empty stomach. 71 patients were randomized and included in the intent to-treat population; 55 completed the 16-week study period (2 weeks washout, 12 weeks treatment, 2 weeks washout). 49% of subjects were taking vitamin D metabolites. RESULTS: Serum phosphorus and PTH rose significantly when patients stopped their phosphate binders during both washout periods. RenaGel and RenaGel with calcium were equally effective at reducing serum phosphorus (mean change 2.4 mg/dL vs. -2.3 mg/dL). RenaGel with calcium was associated with a small increase in serum calcium (mean change 0.3 mg/dL vs. 0.0 mg/dL in RenaGel group, P = 0.09) that was not statistically significant. During the treatment phase, the reduction in PTH tended to be greater in the RenaGel with calcium group (median change -67.0 vs. -22.5 pg/mL in RenaGel group, P = 0.07). Non-users of vitamin D metabolites treated with RenaGel with calcium experienced a significant decrease in PTH (median change -114.5 vs. -22 pg/mL in RenaGel group, P = 0.006). Adverse events were seen with equal frequency in both groups, being generally mild in intensity, and rarely attributable to the drugs. CONCLUSION: We conclude that RenaGel and RenaGel with calcium are similarly effective in the treatment of ESRD related hyperphosphatemia. Provision of supplemental calcium or metabolites of vitamin D with RenaGel may enhance control of hyperparathyroidism. PMID- 9988143 TI - Insulin-like growth factor 1 and 2 serum concentrations in dialysis patients with secondary hyperparathyroidism and adynamic bone disease. AB - BACKGROUND: Insulin-like growth factor-1 and -2 exert well characterized effects on bone metabolism via paracrine and endocrine pathways. However, the role of circulating levels of IGFs and their binding proteins (IGFBP) in renal bone disease is still controversial. PATIENTS AND METHODS: To investigate whether circulating IGFs play a role in the pathogenesis of different forms of renal bone disease, we performed a cross sectional study in 38 stable dialysis patients (32 hemodialysis, 6 peritoneal dialysis). Patients were selected for the type of bone disease according to biochemical bone markers and bone histology. 25 Patients had adynamic bone disease (ABD; defined by plasma iPTH < 1,5 fold the upper limit of normal). Thirteen patients had secondary hyperparathyroidism (sHPT; defined by plasma iPTH > 10 fold the upper limit of normal). Serological diagnosis was confirmed in a subgroup of patients by bone histology (12 patients with type IIa according to Delling, ABD; 9 patients with type IIIb according to Delling, sHPT). Patients with signs or symptoms of aluminum toxicity were excluded from the study. RESULTS: Serum IGF-1 and -2 concentrations were comparable in both groups and were within the reported normal range for an age matched healthy control population. They did not correlate with biochemical markers (iPTH, bAP, osteocalcin) or histological manifestations of renal bone disease. Furthermore, semiquantitative analysis of IGFBP-2 and -3 carried out in patients with bone biopsies did not correlate with biochemical markers or histological indices of renal bone disease. CONCLUSION: In conclusion, in contrast to previous reports, the present data do not confirm a correlation between serological or histological markers of renal osteodystrophy and circulating IGF-1 or -2 or IGFBP-2 and -3. This does not exclude that potential alterations of the local IGF system may play a role in the pathogenesis of uremic bone disease. PMID- 9988144 TI - A prospective study of central venous hemodialysis catheter colonization and peripheral bacteremia. AB - BACKGROUND: Sepsis as a consequence of central venous hemodialysis catheter colonization is a major cause of morbidity in the hemodialysis population. We have previously shown that the majority of catheters become colonized and that this is associated with peripheral bacteremia. The time period over which this colonization occurs is unknown. METHOD: A prospective study of 31 central venous hemodialysis catheters was performed. Central venous blood cultures were taken from the catheter weekly after insertion. When the central cultures became positive, indicating catheter colonization, peripheral venous blood cultures were taken during dialysis to detect peripheral bacteremia. RESULTS: Twenty-one catheters (68%) became colonized before their removal for reasons other than infection (mean time to colonization 27 days, range 5-115 days). Eleven patients (35%) developed peripheral bacteremia with the same organisms (mean time from colonization to bacteremia 32 days, range 5-26 days). Bacteremia only occurred when blood drawn from the catheter cultured more than 3000 colony forming units per ml. CONCLUSIONS: Bacterial colonization of central venous catheters often leads to bacteremia. The time between insertion and colonization is very variable, but is universally present after 16 weeks. The risk of subsequent bacteremia is related not only to time left in situ, but also the degree of colonization. Surveillance cultures would allow clinicians to detect colonization before bacteremia occurs and take preventative measures. PMID- 9988145 TI - Effect of hemodialysis and antiretroviral therapy on plasma viral load in HIV-1 infected hemodialysis patients. AB - BACKGROUND: Plasma viral load has become an important test in predicting the progress of HIV-1 infected patients. The higher the viral load the faster is the progression to AIDS. As HIV-1 infected hemodialysis (HD) patients have higher mortality and morbidity than HIV-1 infected non-dialysis patients, and as all the blood tests in the HD patients are drawn during HD, we measured the effect of HD and antiretroviral therapy on viral load in HIV-1 infected HD patients. PATIENTS AND METHODS: We measured plasma viral load pre-dialysis and post-dialysis in 10 HIV-1 infected HD patients. The viral load was measured using an in vitro quantitative nucleic acid amplification test. We also compared viral load in 8 HIV-1 infected HD patients on one antiretroviral drug with 8 HIV-1 patients on two (6) or three (2) antiretroviral drugs. RESULTS: There was a small reduction in plasma viral load postdialysis in all HIV-1 infected HD patients (45% +/- 5.4, 0.3 log +/- 0.05, p < 0.0004). However, HIV-1 RNA could not be detected in the ultrafiltrate. The patients who were on two or three antiretroviral drugs had lower viral load (8915 +/- 3702 vs. 351440 +/- 101237, p < 0.004) and higher CD4 count (355 +/- 81 vs 82 +/- 39, p < 0.009) than patients on only one antiretroviral drug. CONCLUSION: We conclude that there is a small reduction in plasma viral load in HIV-1 infected hemodialysis patients post-dialysis. As no viral RNA could be detected in the ultrafiltrate, the reduction could be due to nonspecific adsorption of the viral RNA to the dialysis membrane. HIV-1 infected hemodialysis patients who are on two or three antiretroviral drugs had significantly lower viral load and higher CD4 count than patients on only single antiretroviral drug. Therefore a single antiretroviral drug should not be used in treating HIV-1 infected HD patients. PMID- 9988146 TI - Ineffectiveness of dialysis in transthyretin (TTR) clearance in familial amyloid polyneuropathy type I, in spite of lower stability of the TTR Met30 variant. AB - BACKGROUND: Familial Amyloid Polyneuropathy (FAP) is an hereditary form of systemic amyloidosis related to a mutant transthyretin (TTR). The renal disease ranges from proteinuria to end-stage renal failure (ESRF), with replacement of renal function by dialysis. In comparison with FAP patients with normal renal function, the progression of the neurologic disease seems to be retarded in FAP patients on dialysis. PATIENTS AND METHODS: We evaluated the influence of hemodialysis and hemodiafiltration on plasma TTR levels in 6 FAP patients with ESRF, which were on regular hemodialysis for 4 months to 6 years, prior to this study. Hemodialysis was performed over a two-week period, one week with a cellulose triacetate membrane and the other with a polysulfone membrane. In the third week, patients were submitted to hemodiafiltration. Plasma TTR levels were measured at the beginning, 60 min, 120 min, and at the end of each session. We also evaluated the TTR adsorbed by the membrane and in the dialysate. RESULTS: TTR levels did not change significantly with the dialysis. The total amount of TTR adsorbed to the membrane was always < 2 mg and found in the dialysate < 1 mg. Hemodialysis and hemodiafiltration were ineffective in removing TTR, in spite of lower stability of the TTR Met30 variant. CONCLUSION: The protective feature of hemodialysis on the progression of the amyloidosis is not due to the clearance of this abnormal protein from plasma. PMID- 9988147 TI - Diabetic nephropathy with concurrent hepatitis C virus infection related membranoproliferative glomerulonephritis. AB - Diabetes mellitus is often complicated by nephropathy with progression to renal failure. Various forms of glomerulonephritis have been associated with diabetes, sometimes resulting in more rapid deterioration in renal function and occasionally dictating alternative management of these patients in attempts to reverse or contain nephrosis or renal failure. We report the occurrence of Type I membranoproliferative glomerulonephritis (MPGN) with hepatitis C virus (HCV) infection in two patients, in association with diabetic nephropathy. One patient had cryoglobulinemia and cryoglobulin deposits in the kidney. A brief review of the literature on glomerulonephritides occurring in patients with diabetes mellitus is also presented. Clinicians should be aware of the possible occurrence of Type I MPGN and cryoglobulinemia in patients with diabetes mellitus and HCV infection with the appropriate history and physical findings. The therapeutic approach to managing patients with two distinct concurrent lesions remains unresolved. PMID- 9988148 TI - Rapid resolution of tumoral calcinosis after renal transplantation. AB - Three patients with extensive, symptomatic tumoral calcinosis (TC) were studied after renal transplantation. Changes in TC-related symptoms, radiological appearances, calcium, phosphate and intact parathyroid hormone concentrations were recorded. All patients noted an immediate reduction in pain and in 2 patients the TC rapidly resolved. Their TC was not palpable by 6 months and radiographs showed near complete resolution at 12 months. Both developed hypercalcemia and in one patient this was associated with polyuria and renal impairment. Bisphosphonates reduced the hypercalcemia but increasing the corticosteroids had no effect. The third patient remained dialysis dependent due to technical problems and rejection but continued on immunosuppression to preserve residual graft function. His TC improved symptomatically but grew radiologically. These cases demonstrate that rapid resolution of TC may occur after successful renal transplantation and that bisphosphonates can ameliorate the associated hypercalcemia. Early symptomatic benefit may occur without graft function and is probably due to the anti-inflammatory action of corticosteroids. PMID- 9988149 TI - Hand-borne mechanisms of dissemination of hepatitis C virus in dialysis units: basis for new addenda to the present preventive strategies. PMID- 9988150 TI - Clinical impact of stained urine cytology for UTI diagnosis. PMID- 9988151 TI - WT1 nephropathy in a girl with normal karyotype (46,XX) PMID- 9988152 TI - Chronic bacterial inflammation of the gum: the main risk factor for posttransplant gingival hyperplasia? PMID- 9988153 TI - Dialysate CA125 levels in stable peritoneal dialysis patients. PMID- 9988154 TI - An introduction to Ebola: the virus and the disease. PMID- 9988155 TI - Ebola hemorrhagic fever in Kikwit, Democratic Republic of the Congo: clinical observations in 103 patients. AB - During the 1995 outbreak of Ebola hemorrhagic fever in the Democratic Republic of the Congo, a series of 103 cases (one-third of the total number of cases) had clinical symptoms and signs accurately recorded by medical workers, mainly in the setting of the urban hospital in Kikwit. Clinical diagnosis was confirmed retrospectively in cases for which serum samples were available (n = 63, 61% of the cases). The disease began unspecifically with fever, asthenia, diarrhea, headaches, myalgia, arthralgia, vomiting, and abdominal pain. Early inconsistent signs and symptoms included conjunctival injection, sore throat, and rash. Overall, bleeding signs were observed in <45% of the cases. Typically, terminally ill patients presented with obtundation, anuria, shock, tachypnea, and normothermia. Late manifestations, most frequently arthralgia and ocular diseases, occurred in convalescent patients. This series is the most extensive number of cases of Ebola hemorrhagic fever observed during an outbreak. PMID- 9988156 TI - Epidemiologic and clinical aspects of the Ebola virus epidemic in Mosango, Democratic Republic of the Congo, 1995. AB - Twenty-three Ebola hemorrhagic fever (EHF) cases (15 males, 8 females) were identified in Mosango, Democratic Republic of the Congo; 18 (78%) of them died. Eight of the patients came from Kikwit General Hospital and were hospitalized at Mosango General Hospital, 10 acquired their infection at the Mosango hospital and were treated there, and 5 acquired their infection through contact with a hospitalized patient but were never hospitalized themselves. For most of the EHF cases, it was clear that they had been in contact with blood or body fluids of another EHF patient. The Ebola outbreak in Mosango remained relatively small, probably because hygienic conditions in this hospital were relatively good at the time of the outbreak and because as soon as the epidemic was recognized, barrier nursing techniques were used. PMID- 9988157 TI - Ebola hemorrhagic fever and pregnancy. AB - Fifteen (14%) of 105 women with Ebola hemorrhagic fever hospitalized in the isolation unit of the Kikwit General Hospital (Democratic Republic of the Congo) were pregnant. In 10 women (66%) the pregnancy ended with an abortion. In 3 of them, a curettage was performed, and all 3 received a blood transfusion from an apparently healthy person. One woman was prematurely delivered of a stillbirth. Four pregnant women died during the third trimester of their pregnancy. All women presented with severe bleeding. Only 1 survived; she had a curettage because of an incomplete abortion after 8 months of amenorrhea. The mortality among pregnant women with Ebola hemorrhagic fever (95.5%) was slightly but not significantly higher than the overall mortality observed during the Ebola epidemic in Kikwit (77%; 245/316 infected persons). PMID- 9988158 TI - Late ophthalmologic manifestations in survivors of the 1995 Ebola virus epidemic in Kikwit, Democratic Republic of the Congo. AB - Three (15%) of 20 survivors of the 1995 Ebola outbreak in the Democratic Republic of the Congo enrolled in a follow-up study and 1 other survivor developed ocular manifestations after being asymptomatic for 1 month. Patients complained of ocular pain, photophobia, hyperlacrimation, and loss of visual acuity. Ocular examination revealed uveitis in all 4 patients. All patients improved with a topical treatment of 1% atropine and steroids. PMID- 9988159 TI - Isolated case of Ebola hemorrhagic fever with mucormycosis complications, Kinshasa, Democratic Republic of the Congo. AB - A patient with undiagnosed Ebola (EBO) hemorrhagic fever (EHF) was transferred from Kikwit to a private clinic in Kinshasa, Democratic Republic of the Congo. A diagnosis of EHF was suspected on clinical grounds and was confirmed by detection of EBO virus-specific IgM and IgG in serum of the patient. During the course of the disease, although she had no known predisposing factors, the patient developed a periorbital mucormycosis abscess on eyelid tissue that was biopsied during surgical drainage; the abscess was histologically confirmed. Presence of EBO antigen was also detected by specific immunohistochemistry on the biopsied tissue. The patient survived the EBO infection but had severe sequelae associated with the mucormycosis. Standard barrier-nursing precautions were taken upon admission and upgraded when EHF was suspected; there was no secondary transmission of the disease. PMID- 9988160 TI - Treatment of Ebola hemorrhagic fever with blood transfusions from convalescent patients. International Scientific and Technical Committee. AB - Between 6 and 22 June 1995, 8 patients in Kikwit, Democratic Republic of the Congo, who met the case definition used in Kikwit for Ebola (EBO) hemorrhagic fever, were transfused with blood donated by 5 convalescent patients. The donated blood contained IgG EBO antibodies but no EBO antigen. EBO antigens were detected in all the transfusion recipients just before transfusion. The 8 transfused patients had clinical symptoms similar to those of other EBO patients seen during the epidemic. All were seriously ill with severe asthenia, 4 presented with hemorrhagic manifestations, and 2 became comatose as their disease progressed. Only 1 transfused patient (12.5%) died; this number is significantly lower than the overall case fatality rate (80%) for the EBO epidemic in Kikwit and than the rates for other EBO epidemics. The reason for this low fatality rate remains to be explained. The transfused patients did receive better care than those in the initial phase of the epidemic. Plans should be made to prepare for a more thorough evaluation of passive immune therapy during a new EBO outbreak. PMID- 9988161 TI - Ebola hemorrhagic fever, Democratic Republic of the Congo, 1995: determinants of survival. AB - In May 1995, an international team characterized and contained an outbreak of Ebola hemorrhagic fever in Kikwit, Democratic Republic of the Congo. This study reports the descriptive features of this outbreak along with a statistical analysis of the outbreak data. Proportional hazards analysis was used to examine the effect of age, phase of the outbreak, and sex on the risk of death, and a conditional probability analysis was used to examine the effectiveness of whole blood transfusion from convalescent patients on survival. Two hundred fifty case patients (80.7%) died. The main predictor of survival in the proportional hazards model was age. No statistical evidence of a survival benefit of transfusion of blood from convalescent patients was evident after adjusting for age, sex, and the days since onset of symptoms (P = .1713). PMID- 9988162 TI - Clinical, virologic, and immunologic follow-up of convalescent Ebola hemorrhagic fever patients and their household contacts, Kikwit, Democratic Republic of the Congo. Commission de Lutte contre les Epidemies a Kikwit. AB - A cohort of convalescent Ebola hemorrhagic fever (EHF) patients and their household contacts (HHCs) were studied prospectively to determine if convalescent body fluids contain Ebola virus and if secondary transmission occurs during convalescence. Twenty-nine EHF convalescents and 152 HHCs were monitored for up to 21 months. Blood specimens were obtained and symptom information was collected from convalescents and their HHCs; other body fluid specimens were also obtained from convalescents. Arthralgias and myalgia were reported significantly more often by convalescents than HHCs. Evidence of Ebola virus was detected by reverse transcription-polymerase chain reaction in semen specimens up to 91 days after disease onset; however, these and all other non-blood body fluids tested negative by virus isolation. Among 81 initially antibody negative HHCs, none became antibody positive. Blood specimens of 5 HHCs not identified as EHF patients were initially antibody positive. No direct evidence of convalescent-to-HHC transmission of EHF was found, although the semen of convalescents may be infectious. The existence of initially antibody-positive HHCs suggests that mild cases of Ebola virus infection occurred and that the full extent of the EHF epidemic was probably underestimated. PMID- 9988164 TI - Human infection due to Ebola virus, subtype Cote d'Ivoire: clinical and biologic presentation. AB - In November 1994 after 15 years of epidemiologic silence, Ebola virus reemerged in Africa and, for the first time, in West Africa. In Cote d'Ivoire, a 34-year old female ethologist was infected while conducting a necropsy on a wild chimpanzee. Eight days later, the patient developed a syndrome that did not respond to antimalarial drugs and was characterized by high fever, headache, chills, myalgia, and cough. The patient had abdominal pain, diarrhea, vomiting, and a macular rash, and was repatriated to Switzerland. The patient suffered from prostration and weight loss but recovered without sequelae. Laboratory findings included aspartate aminotransferase and alanine aminotransferase activity highly elevated, thrombocytopenia, lymphopenia, and, subsequently, neutrophilia. A new subtype of Ebola was isolated from the patient's blood on days 4 and 8. No serologic conversion was detected among contact persons in Cote d'Ivoire (n = 22) or Switzerland (n = 52), suggesting that infection-control precautions were satisfactory. PMID- 9988163 TI - A novel immunohistochemical assay for the detection of Ebola virus in skin: implications for diagnosis, spread, and surveillance of Ebola hemorrhagic fever. Commission de Lutte contre les Epidemies a Kikwit. AB - Laboratory diagnosis of Ebola hemorrhagic fever (EHF) is currently performed by virus isolation and serology and can be done only in a few high-containment laboratories worldwide. In 1995, during the EHF outbreak in the Democratic Republic of Congo, the possibility of using immunohistochemistry (IHC) testing of formalin-fixed postmortem skin specimens was investigated as an alternative diagnostic method for EHF. Fourteen of 19 cases of suspected EHF met the surveillance definition for EHF and were positive by IHC. IHC, serologic, and virus isolation results were concordant for all EHF and non-EHF cases. IHC and electron microscopic examination showed that endothelial cells, mononuclear phagocytes, and hepatocytes are main targets of infection, and IHC showed an association of cellular damage with viral infection. The finding of abundant viral antigens and particles in the skin of EHF patients suggests an epidemiologic role for contact transmission. IHC testing of formalin-fixed skin specimens is a safe, sensitive, and specific method for laboratory diagnosis of EHF and should be useful for EHF surveillance and prevention. PMID- 9988165 TI - Histopathological and immunohistochemical studies of lesions associated with Ebola virus in a naturally infected chimpanzee. AB - Lesions caused by the Cote d'Ivoire subtype of Ebola virus in a naturally infected young chimpanzee were characterized by histopathological and immunohistochemical methods. The predominant lesions consisted of multifocal necrosis in the liver and diffuse fibrinoid necrosis in the red pulp of the spleen. In these sites, macrophages contained large eosinophilic intracytoplasmic inclusion bodies. Immunohistochemical staining indicated that macrophages were a major site of viral replication. The absence of bronchiolar and pulmonary lesions and the paucity of antigen-containing macrophages in the lung suggested that aerosol transmission by this animal was unlikely. There were necrotic foci and antigen-containing macrophages in intestinal lymph nodes, in association with lesions caused by intestinal parasites, suggesting the possibility of virus entry through the digestive tract. PMID- 9988166 TI - Ebola between outbreaks: intensified Ebola hemorrhagic fever surveillance in the Democratic Republic of the Congo, 1981-1985. AB - Surveillance for Ebola hemorrhagic fever was conducted in the Democratic Republic of the Congo from 1981 to 1985 to estimate the incidence of human infection. Persons who met the criteria of one of three different case definitions were clinically evaluated, and blood was obtained for antibody confirmation by IFA. Contacts of each case and 4 age- and sex-matched controls were also clinically examined and tested for immunofluorescent antibody. Twenty-one cases of Ebola infection (persons with an antibody titer of > or = 1:64, or lower if they fit the clinical case definition) were identified, with a maximum 1-year incidence of 9 and a case fatality rate of 43%. Cases occurred throughout the year, but most (48%) occurred early in the rainy season. Fifteen percent of contacts had antibody titers > or =1:64 to Ebola virus, compared with 1% of controls (P < .0001). Results suggest that Ebola virus periodically emerges from nature to infect humans, that person-to-person transmission is relatively limited, and that amplification to large epidemics is unusual. PMID- 9988167 TI - Ebola hemorrhagic fever outbreaks in Gabon, 1994-1997: epidemiologic and health control issues. AB - From the end of 1994 to the beginning of 1995, 49 patients with hemorrhagic symptoms were hospitalized in the Makokou General Hospital in northeastern Gabon. Yellow fever (YF) virus was first diagnosed in serum by use of polymerase chain reaction followed by blotting, and a vaccination campaign was immediately instituted. The epidemic, known as the fall 1994 epidemic, ended 6 weeks later. However, some aspects of this epidemic were atypical of YF infection, so a retrospective check for other etiologic agents was undertaken. Ebola (EBO) virus was found to be present concomitantly with YF virus in the epidemic. Two other epidemics (spring and fall 1996) occurred in the same province. GP and L genes of EBO virus isolates from all three epidemics were partially sequenced, which showed a difference of <0.1% in the base pairs. Sequencing also showed that all isolates were very similar to subtype Zaire EBO virus isolates from the Democratic Republic of the Congo. PMID- 9988168 TI - The reemergence of Ebola hemorrhagic fever, Democratic Republic of the Congo, 1995. Commission de Lutte contre les Epidemies a Kikwit. AB - In May 1995, an international team characterized and contained an outbreak of Ebola hemorrhagic fever (EHF) in Kikwit, Democratic Republic of the Congo. Active surveillance was instituted using several methods, including house-to-house search, review of hospital and dispensary logs, interview of health care personnel, retrospective contact tracing, and direct follow-up of suspect cases. In the field, a clinical case was defined as fever and hemorrhagic signs, fever plus contact with a case-patient, or fever plus at least 3 of 10 symptoms. A total of 315 cases of EHF, with an 81% case fatality, were identified, excluding 10 clinical cases with negative laboratory results. The earliest documented case patient had onset on 6 January, and the last case-patient died on 16 July. Eighty cases (25%) occurred among health care workers. Two individuals may have been the source of infection for >50 cases. The outbreak was terminated by the initiation of barrier-nursing techniques, health education efforts, and rapid identification of cases. PMID- 9988169 TI - Transmission of Ebola hemorrhagic fever: a study of risk factors in family members, Kikwit, Democratic Republic of the Congo, 1995. Commission de Lutte contre les Epidemies a Kikwit. AB - The surviving members of 27 households in which someone had been infected with Ebola virus were interviewed in order to define the modes of transmission of Ebola hemorrhagic fever (EHF). Of 173 household contacts of the primary cases, 28 (16%) developed EHF. All secondary cases had direct physical contact with the ill person (rate ratio [RR], undefined; P < .001), and among those with direct contact, exposure to body fluids conferred additional risk (RR, 3.6; 95% confidence interval [CI], 1.9-6.8). After adjusting for direct contact and exposure to body fluids, adult family members, those who touched the cadaver, and those who were exposed during the late hospital phase were at additional risk. None of the 78 household members who had no physical contact with the case during the clinical illness were infected (upper 95% CI, 4%). EHF is transmitted principally by direct physical contact with an ill person or their body fluids during the later stages of illness. PMID- 9988170 TI - Ebola hemorrhagic fever, Kikwit, Democratic Republic of the Congo, 1995: risk factors for patients without a reported exposure. AB - In 1995, 316 people became ill with Ebola hemorrhagic fever (EHF) in Kikwit, Democratic Republic of the Congo. The exposure source was not reported for 55 patients (17%) at the start of this investigation, and it remained unknown for 12 patients after extensive epidemiologic evaluation. Both admission to a hospital and visiting a person with fever and bleeding were risk factors associated with infection. Nineteen patients appeared to have been exposed while visiting someone with suspected EHF, although they did not provide care. Fourteen of the 19 reported touching the patient with suspected EHF; 5 reported that they had no physical contact. Although close contact while caring for an infected person was probably the major route of transmission in this and previous EHF outbreaks, the virus may have been transmitted by touch, droplet, airborne particle, or fomite; thus, expansion of the use of barrier techniques to include casual contacts might prevent or mitigate future epidemics. PMID- 9988171 TI - Serologic survey among hospital and health center workers during the Ebola hemorrhagic fever outbreak in Kikwit, Democratic Republic of the Congo, 1995. AB - From May to July 1995, a serologic and interview survey was conducted to describe Ebola hemorrhagic fever (EHF) among personnel working in 5 hospitals and 26 health care centers in and around Kikwit, Democratic Republic of the Congo. Job specific attack rates estimated for Kikwit General Hospital, the epicenter of the EHF epidemic, were 31% for physicians, 11% for technicians/room attendants, 10% for nurses, and 4% for other workers. Among 402 workers who did not meet the EHF case definition, 12 had borderline positive antibody test results; subsequent specimens from 4 of these tested negative. Although an old infection with persistent Ebola antibody production or a recent atypical or asymptomatic infection cannot be ruled out, if they occur at all, they appear to be rare. This survey demonstrated that opportunities for transmission of Ebola virus to personnel in health facilities existed in Kikwit because blood and body fluid precautions were not being universally followed. PMID- 9988172 TI - Prevalence of IgG antibodies to Ebola virus in individuals during an Ebola outbreak, Democratic Republic of the Congo, 1995. AB - During the 1995 outbreak of Ebola (EBO) hemorrhagic fever in Kikwit, Democratic Republic of Congo, two surveys using a new ELISA for EBO (subtype Zaire) virus antigen were conducted to assess the prevalence of EBO IgG antibodies among residents of Kikwit and the surrounding area. The first study determined the proportion of antibody-positive individuals who were self-identified forest and city workers from the Kikwit area. Serum samples from 9 (2.2%) of 414 workers had IgG EBO antibodies. The second study determined the proportion of EBO antibody positive individuals who lived in villages surrounding Kikwit. The prevalence of IgG EBO antibodies in this population was 9.3% (151161). The difference in the overall prevalence of EBO antibodies may indicate that villagers have a greater chance of exposure to EBO virus compared with those living in and in close proximity to cities. PMID- 9988174 TI - Epidemiology of Ebola (subtype Reston) virus in the Philippines, 1996. AB - Ebola (subtype Reston [EBO-R]) virus infection was detected in macaques imported into the United States from the Philippines in March 1996. Studies were initiated in the Philippines to identify the source of the virus among monkey-breeding and export facilities, to establish surveillance and testing, and to assess the risk and significance of EBO-R infections in humans who work in these facilities. Over a 5-month period, acutely infected animals were found at only one facility, as determined using Ebola antigen detection. Three of 1732 monkeys and 1 of 246 animal handlers tested had detectable antibodies; all were from the same facility, which was the source of infected monkeys imported to the United States. Virus transmission, which was facilitated by poor infection-control practices, continued for several months in one facility and was stopped only when the facility was depopulated. None of the 246 employees of the facilities or 4 contacts of previously antibody-positive individuals reported an Ebola-like illness. This investigation suggests that human EBO-R infection is rare. PMID- 9988173 TI - Ebola (subtype Reston) virus among quarantined nonhuman primates recently imported from the Philippines to the United States. AB - In April 1996, laboratory testing of imported nonhuman primates (as mandated by quarantine regulations) identified 2 cynomolgus macaques (Macaca fascicularis) infected with Ebola (subtype Reston) virus in a US-registered quarantine facility. The animals were part of a shipment of 100 nonhuman primates recently imported from the Philippines. Two additional infected animals, who were thought to be in the incubation phase, were identified among the remaining 48 animals in the affected quarantine room. The other 50 macaques, who had been held in a separate isolation room, remained asymptomatic, and none of these animals seroconverted during an extended quarantine period. Due to the rigorous routine safety precautions, the facility personnel had no unprotected exposures and remained asymptomatic, and no one seroconverted. The mandatory quarantine and laboratory testing requirements, put in place after the original Reston outbreak in 1989-1990, were effective for detecting and containing Ebola virus infection in newly imported nonhuman primates and minimizing potential human transmission. PMID- 9988175 TI - Ebola virus outbreak among wild chimpanzees living in a rain forest of Cote d'Ivoire. AB - An outbreak of Ebola in nature is described for the first time. During a few weeks in November 1994, approximately 25% of 43 members of a wild chimpanzee community disappeared or were found dead in the Tai National Park, Cote d'Ivoire. A retrospective cohort study was done on the chimpanzee community. Laboratory procedures included histology, immunohistochemistry, bacteriology, and serology. Ebola-specific immunohistochemical staining was positive for autopsy tissue sections from 1 chimpanzee. Demographic, epidemiologic, and ecologic investigations were compatible with a point-source epidemic. Contact activities associated with a case (e.g., touching dead bodies or grooming) did not constitute significant risk factors, whereas consumption of meat did. The relative risk of meat consumption was 5.2 (95% confidence interval, 1.3-21.1). A similar outbreak occurred in November 1992 among the same community. A high mortality rate among apes tends to indicate that they are not the reservoir for the disease causing the illness. These points will have to be investigated by additional studies. PMID- 9988176 TI - Ecology of Marburg and Ebola viruses: speculations and directions for future research. AB - Marburg and virulent Ebola viruses are maintained in hosts that are rare and have little contact with humans or do not readily transmit virus. Bats (particularly solitary microchiropteran species) are leading contenders as reservoir hosts. Virus transfer to humans occurs by contact with the primary reservoir or via an intermediate animal that acquired infection from the reservoir and is, in turn, hunted by humans. An interesting possibility is that filoviruses may be arthropod or plant viruses, with non-blood-feeding arthropods transmitting the virus to intermediate hosts or humans during oral ingestion or envenomation. Paradoxically, in Africa, Ebola virus disease has high lethality and high seroprevalence as determined by the IFA test. If the seroreactivity is confirmed by more specific tests, then the Ebola virus serogroup in Africa probably contains an antigenically cross-reactive, enzootic, nonpathogenic agent(s). Such viruses may have separate life cycles or may give rise to virulent strains by mutation. PMID- 9988177 TI - A search for Ebola virus in animals in the Democratic Republic of the Congo and Cameroon: ecologic, virologic, and serologic surveys, 1979-1980. Ebola Virus Study Teams. AB - More than 30 years after the first outbreak of Marburg virus disease in Germany and Yugoslavia and 20 years after Ebola hemorrhagic fever first occurred in central Africa, the natural history of filoviruses remains unknown. In 1979 and 1980, animals in the Democratic Republic of the Congo and Cameroon were collected during the dry season near the site of the 1976 Ebola hemorrhagic fever epidemic. The study objectives were to identify local animals and search for evidence of Ebola virus in their tissues. A total of 1664 animals representing 117 species was collected, including >400 bats and 500 rodents. Vero and CV-1 cells and IFA and RIA were used for virus and antibody detection, respectively. No evidence of Ebola virus infection was found. This study was limited in time and animal collections and excluded insects and plants. Long-term, prospective, multidisciplinary comparative studies will yield more information than will repeat short forays on the ecology of filoviruses. PMID- 9988178 TI - Field investigations of an outbreak of Ebola hemorrhagic fever, Kikwit, Democratic Republic of the Congo, 1995: arthropod studies. AB - During the final weeks of a 6-month epidemic of Ebola hemorrhagic fever in Kikwit, Democratic Republic of the Congo, an extensive collection of arthropods was made in an attempt to learn more of the natural history of the disease. A reconstruction of the activities of the likely primary case, a 42-year-old man who lived in the city, indicated that he probably acquired his infection in a partly forested area 15 km from his home. Collections were made throughout this area, along the route he followed from the city, and at various sites in the city itself. No Ebola virus was isolated, but a description of the collections and the ecotopes involved is given for comparison with future studies of other outbreaks. PMID- 9988179 TI - Search for the Ebola virus reservoir in Kikwit, Democratic Republic of the Congo: reflections on a vertebrate collection. AB - A 3-month ecologic investigation was done to identify the reservoir of Ebola virus following the 1995 outbreak in Kikwit, Democratic Republic of the Congo. Efforts focused on the fields where the putative primary case had worked but included other habitats near Kikwit. Samples were collected from 3066 vertebrates and tested for the presence of antibodies to Ebola (subtype Zaire) virus: All tests were negative, and attempts to isolate Ebola virus were unsuccessful. The investigation was hampered by a lack of information beyond the daily activities of the primary case, a lack of information on Ebola virus ecology, which precluded the detailed study of select groups of animals, and sample-size limitations for rare species. The epidemiology of Ebola hemorrhagic fever suggests that humans have only intermittent contact with the virus, which complicates selection of target species. Further study of the epidemiology of human outbreaks to further define the environmental contact of primary cases would be of great value. PMID- 9988180 TI - Detection and molecular characterization of Ebola viruses causing disease in human and nonhuman primates. AB - Ebola (EBO) viruses were detected in specimens obtained during the hemorrhagic fever outbreak among humans in Kikwit, Democratic Republic of the Congo (DRC), in 1995 (subtype Zaire) and during an outbreak of disease in cynomolgus macaques in Alice, Texas, and the Philippines in 1996 (subtype Reston). Reverse transcriptase polymerase chain reaction assays were developed and proven effective for detecting viral RNA in body fluids and tissues of infected individuals. Little change was seen in the nucleotide or deduced amino acid sequences of the glycoprotein (GP) of these EBO virus subtypes compared with those of their original representatives (i.e., the 1976 Yambuku, DRC, EBO isolate [subtype Zaire] and the 1989 Philippines and Reston, Virginia, isolates [subtype Reston]). The nonstructural secreted GP (SGP), the primary product of the GP gene, was more highly conserved than the structural GP, indicating different functional roles or evolutionary constraints for these proteins. Significant amounts of SGP were detected in acutely infected humans. PMID- 9988181 TI - Persistence and genetic stability of Ebola virus during the outbreak in Kikwit, Democratic Republic of the Congo, 1995. AB - Ebola virus persistence was examined in body fluids from 12 convalescent patients by virus isolation and reverse transcription-polymerase chain reaction (RT-PCR) during the 1995 Ebola hemorrhagic fever outbreak in Kikwit, Democratic Republic of the Congo. Virus RNA could be detected for up to 33 days in vaginal, rectal, and conjunctival swabs of 1 patient and up to 101 days in the seminal fluid of 4 patients. Infectious virus was detected in 1 seminal fluid sample obtained 82 days after disease onset. Sequence analysis of an RT-PCR fragment of the most variable region of the glycoprotein gene amplified from 9 patients revealed no nucleotide changes. The patient samples were selected so that they would include some from a suspected line of transmission with at least three human-to-human passages, some from 5 survivors and 4 deceased patients, and 2 from patients who provided multiple samples through convalescence. There was no evidence of different virus variants cocirculating during the outbreak or of genetic variation accumulating during human-to-human passage or during prolonged persistence in individual patients. PMID- 9988182 TI - Clinical virology of Ebola hemorrhagic fever (EHF): virus, virus antigen, and IgG and IgM antibody findings among EHF patients in Kikwit, Democratic Republic of the Congo, 1995. AB - Ebola hemorrhagic fever (EHF) patients treated at Kikwit General Hospital during the 1995 outbreak were tested for viral antigen, IgG and IgM antibody, and infectious virus. Viral antigen could be detected in virtually all patients during the acute phase of illness, while antibody was not always detectable before death. Virus was also isolated from patients during the course of their febrile illness, but attempts to quantify virus in Vero E6 cells by standard plaque assay were often unsuccessful. IgG and IgM antibody appeared at approximately the same time after disease onset (8-10 days), but IgM persisted for a much shorter period among the surviving convalescent patients. IgG antibody was detectable in surviving patients through about 2 years after onset, the latest time that samples were obtained. Detection of Ebola virus antigens or virus isolation appears to be the most reliable means of diagnosis for patients with suspected acute EHF, since patients with this often-fatal disease (80% mortality) may not develop detectable antibodies before death. PMID- 9988183 TI - Markedly elevated levels of interferon (IFN)-gamma, IFN-alpha, interleukin (IL) 2, IL-10, and tumor necrosis factor-alpha associated with fatal Ebola virus infection. AB - The role of immune mechanisms in the pathogenesis of Ebola hemorrhagic fever (EHF) remains to be elucidated. In this report, the serum cytokine levels of patients who died of EHF were compared with those of patients who recovered and those of control patients. A marked elevation of interferon (IFN)-gamma levels (>100 pg/mL) was observed in sequential serum samples from all fatal EHF cases compared with patients who recovered or controls. Markedly elevated serum levels of interleukin (IL)-2, IL-10, tumor necrosis factor (TNF)-alpha, and IFN-alpha were also noted in fatal EHF cases; however, they had a greater degree of variability. No differences were noted in serum levels of IL-4 and IL-6. mRNA quantitation from blood clots of the same patients showed relatively elevated levels of TNF-alpha and IFN-alpha in samples from EHF patients. Taken together, these results suggest that a high degree of immune activation accompanies and potentially contributes to a fatal outcome in EHF patients. PMID- 9988184 TI - ELISA for the detection of antibodies to Ebola viruses. AB - EIAs for IgG and IgM antibodies directed against Ebola (EBO) viral antigens have been developed and evaluated using sera of animals and humans surviving infection with EBO viruses. The IgM capture assay detected anti-EBO (subtype Reston) antibodies in the sera of 5 of 5 experimentally infected animals at the time they succumbed to lethal infections. IgM antibodies were also detected in the serum of a human who was infected with EBO (subtype Reston) during a postmortem examination of an infected monkey. The antibody was detectable as early as day 6 after infection in experimentally infected animals and persisted for <90 days. The IgG response was less rapid; however, it persisted for >400 days in 3 animals who survived infection, and it persisted for approximately 10 years after infection in the sera of 2 humans. Although these data are limited by the number of sera available for verification, the IgM assay seems to have great promise as a diagnostic tool. Furthermore the long-term persistence of the IgG antibodies measured by this test strongly suggests that the ELISA will be useful in field investigations of EBO virus. PMID- 9988185 TI - An analysis of features of pathogenesis in two animal models of Ebola virus infection. AB - Virus reproduction and the time course of changes in liver and kidney functions and in the blood clotting system were studied in the visceral organs of green monkeys and baboons infected with Ebola virus (subtype Zaire). It was shown that monocytes and macrophages were the first cells to be infected with the virus, followed by hepatocytes, adrenocorticocytes, fibroblasts, and endotheliocytes. The early and late pathologic changes in the monkey organs are described. Biochemical data on changes in blood clotting and liver and kidney functions in the course of the infection are presented. The responses of blood clotting and vascular permeability were species specific: Fibrin deposited in blood vessels in green monkeys, while hemorrhages developed in baboons. The results show that species-specific features of monkeys must be taken into account when choosing an experimental model for studying Ebola virus infection. PMID- 9988186 TI - Pathogenesis of experimental Ebola virus infection in guinea pigs. AB - The subtype Zaire of Ebola (EBO) virus (Mayinga strain) was adapted to produce lethal infections in guinea pigs. In many ways, the disease was similar to EBO infections in nonhuman primates and humans. The guinea pig model was used to investigate the pathologic events in EBO infection that lead to death. Analytical methods included immunohistochemistry, in situ hybridization, and electron microscopy. Cells of the mononuclear phagocyte system, primarily macrophages, were identified as the early and sustained targets of EBO virus. During later stages of infection, interstitial fibroblasts in various tissues were infected, and there was evidence of endothelial cell infection and fibrin deposition. The distribution of lesions, hematologic profiles, and increases in serum biochemical enzymes associated with EBO virus infection in guinea pigs was similar to reported findings in experimentally infected nonhuman primates and naturally infected humans. PMID- 9988187 TI - Preparation and use of hyperimmune serum for prophylaxis and therapy of Ebola virus infections. AB - To obtain hyperimmune serum appropriate for the treatment of filovirus infection, methods were developed to immunize nonsusceptible animals with live Ebola (EBO) virus preparations. Immune plasma with high ELISA and neutralization-specific antibody titers was obtained by multiple immunization of sheep and goats with preparations of live EBO virus. Goat immunoglobulin was prepared by Cohn's method and tested on guinea pigs, using an EBO virus strain that is highly pathogenic for guinea pigs. Prophylaxis with these immunoglobulins within 48 h after infection was effective in challenge experiments, with a log10 prophylaxis index as high as 1.92+/-0.52. Other studies have shown that equine anti-EBO virus immunoglobulins worked well in baboons. The goat immunoglobulins were also tested in preclinical trials on laboratory animals; after being positively evaluated, they were administered to volunteers in clinical trials for biologic safety and reactivity, and they were administered to researchers suspected of becoming infected with EBO during their experimental work. These immunoglobulins may be useful for the emergency treatment of persons accidentally infected with EBO. PMID- 9988188 TI - Evaluation of immune globulin and recombinant interferon-alpha2b for treatment of experimental Ebola virus infections. AB - A passive immunization strategy for treating Ebola virus infections was evaluated using BALB/ c mice, strain 13 guinea pigs, and cynomolgus monkeys. Guinea pigs were completely protected by injection of hyperimmune equine IgG when treatment was initiated early but not after viremia had developed. In contrast, mice were incompletely protected even when treatment was initiated on day 0, the day of virus inoculation. In monkeys treated with one dose of IgG on day 0, onset of illness and viremia was delayed, but all treated animals died. A second dose of IgG on day 5 had no additional beneficial effect. Pretreatment of monkeys delayed onset of viremia and delayed death several additional days. Interferon-alpha2b (2 x 10(7) IU/kg/day) had a similar effect in monkeys, delaying viremia and death by only several days. Effective treatment of Ebola infections may require a combination of drugs that inhibit viral replication in monocyte/macrophage-like cells while reversing the pathologic effects (e.g., coagulopathy) consequent to this replication. PMID- 9988189 TI - Recombinant human monoclonal antibodies to Ebola virus. AB - Human Fab (IgG1kappa) phage display libraries were constructed from bone marrow RNA from 2 donors who recovered from infection with Ebola (EBO) virus during the 1995 outbreak in Kikwit, Democratic Republic of the Congo. The libraries were initially panned against a radiation-inactivated EBO virus-infected Vero cell lysate, but only weak binders were identified. In contrast, panning against secreted EBO glycoprotein (SGP) resulted in Fabs showing very strong reactivity with SGP in ELISA. These Fabs also reacted with a virion membrane preparation. The Fabs were strongly positive in IFAs with cells infected with EBO (subtype Zaire) virus but negative with uninfected cells, with a characteristic punctate staining pattern in the cytoplasm. The Fabs showed weak or no reactivity with the virus cell lysate although donor serum did react. The Fabs are now being characterized in structural and functional terms. Major interest will focus on the ability of antibodies to neutralize EBO virus and, later, to protect animals against infection. PMID- 9988190 TI - Antiviral drug therapy of filovirus infections: S-adenosylhomocysteine hydrolase inhibitors inhibit Ebola virus in vitro and in a lethal mouse model. AB - Ebola (subtype Zaire) viral replication was inhibited in vitro by a series of nine nucleoside analogue inhibitors of S-adenosylhomocysteine hydrolase, an important target for antiviral drug development. Adult BALB/c mice lethally infected with mouse-adapted Ebola virus die 5-7 days after infection. Treatment initiated on day 0 or 1 resulted in dose-dependent protection, with mortality completely prevented at doses > or =0.7 mg/kg every 8 h. There was significant protection (90%) when treatment was begun on day 2, at which time, the liver had an average titer of 3 x 10(5) pfu/g virus and the spleen had 2 x 10(6) pfu/g. Treatment with 2.2 mg/kg initiated on day 3, when the liver had an average titer of 2 x 10(7) pfu/g virus and the spleen had 2 x 10(8) pfu/g, resulted in 40% survival. As reported here, Carbocyclic 3-deazaadenosine is the first compound demonstrated to cure animals from this otherwise lethal Ebola virus infection. PMID- 9988191 TI - A mouse model for evaluation of prophylaxis and therapy of Ebola hemorrhagic fever. AB - The Zaire subtype of Ebola virus (EBO-Z) is lethal for newborn mice, but adult mice are resistant to the virus, which prevents their use as an animal model of lethal Ebola infection. We serially passed EBO-Z virus in progressively older suckling mice, eventually obtaining a plaque-purified virus that was lethal for mature, immunocompetent BALB/c and C57BL/6 inbred and ICR (CD-1) outbred mice. Pathologic changes in the liver and spleen of infected mice resembled those in EBO-Z-infected primates. Virus titers in these tissues reached 10(9) pfu/g. The LD50 of mouse-adapted EBO-Z virus inoculated into the peritoneal cavity was approximately 1 virion. Mice were resistant to large doses of the same virus inoculated subcutaneously, intradermally, or intramuscularly. Mice injected peripherally with mouse-adapted or intraperitoneally with non-adapted EBO-Z virus resisted subsequent challenge with mouse-adapted virus. PMID- 9988192 TI - Ebola outbreak in Kikwit, Democratic Republic of the Congo: discovery and control measures. AB - The Ebola epidemic in Kikwit, Democratic Republic of the Congo, was recognized because of a nosocomial outbreak in Kikwit General Hospital. Initially, a diagnosis of shigella infection was suspected because many patients presented with bloody diarrhea. On 4 May 1995, blood samples from 14 acutely ill patients were sent to the Centers for Disease Control and Prevention (Atlanta), and on 9 May, a diagnosis of Ebola hemorrhagic fever was confirmed. The major disease control measures that were undertaken were the isolation of patients in a quarantine ward at Kikwit General Hospital, the distribution of protective equipment to health care workers and family members caring for Ebola patients, the use of barrier nursing techniques, the distribution of health education material, active and passive case finding, and the burying of the deceased in plastic bags by a trained team of Red Cross volunteers who wore gloves and protective clothing. PMID- 9988193 TI - Interventions to control virus transmission during an outbreak of Ebola hemorrhagic fever: experience from Kikwit, Democratic Republic of the Congo, 1995. AB - On 6 May 1995, the Medecins sans Frontieres (MSF) coordinator in Kinshasa, Democratic Republic of the Congo (DRC), received a request for assistance for what was believed to be a concurrent outbreak of bacillary dysentery and viral hemorrhagic fever (suspected Ebola hemorrhagic fever [EHF]) in the town of Kikwit, DRC. On 11 May, the MSF intervention team assessed Kikwit General Hospital. This initial assessment revealed a nonfunctional isolation ward for suspected EHF cases; a lack of water and electricity; no waste disposal system; and no protective gear for medical staff. The priorities set by MSF were to establish a functional isolation ward to deal with EHF and to distribute protective supplies to individuals who were involved with patient care. Before the intervention, 67 health workers contracted EHF; after the initiation of control measures, just 3 cases were reported among health staff and none among Red Cross volunteers involved in body burial. PMID- 9988194 TI - Organization of patient care during the Ebola hemorrhagic fever epidemic in Kikwit, Democratic Republic of the Congo, 1995. AB - In contrast with procedures in previous Ebola outbreaks, patient care during the 1995 outbreak in Kikwit, Democratic Republic of the Congo, was centralized for a large number of patients. On 4 May, before the diagnosis of Ebola hemorrhagic fever (EHF) was confirmed by the Centers for Disease Control and Prevention, an isolation ward was created at Kikwit General Hospital. On 11 May, an international scientific and technical committee established as a priority the improvement of hygienic conditions in the hospital and the protection of health care workers and family members; to this end, protective equipment was distributed and barrier-nursing techniques were implemented. For patients living far from Kikwit, home care was organized. Initially, hospitalized patients were given only oral treatments; however, toward the end of the epidemic, infusions and better nutritional support were given, and 8 patients received blood from convalescent EHF patients. Only 1 of the transfusion patients died (12.5%). It is expected that with improved medical care, the case fatality rate of EHF could be reduced. PMID- 9988195 TI - Long-term disease surveillance in Bandundu region, Democratic Republic of the Congo: a model for early detection and prevention of Ebola hemorrhagic fever. AB - After the large-scale outbreak of Ebola hemorrhagic fever (EHF) in Bandundu region, Democratic Republic of the Congo, a program was developed to help detect and prevent future outbreaks of EHF in the region. The long-term surveillance and prevention strategy is based on early recognition by physicians, immediate initiation of enhanced barrier-nursing practices, and the use of an immunohistochemical diagnostic test performed on formalin-fixed skin specimens of patients who die of suspected viral hemorrhagic fever. The program was implemented in September 1995 during a 4-day workshop with 28 local physicians representing 17 of 22 health zones in the region. Specimen collection kits were distributed to clinics in participating health zones, and a follow-up evaluation was conducted after 6 months. The use of a formalin-fixed skin specimen for laboratory confirmation of EHF can provide an appropriate method for EHF surveillance when linked with physician training, use of viral hemorrhagic fever isolation precautions, and follow-up investigation. PMID- 9988196 TI - US policy for disease control among imported nonhuman primates. AB - In 1990, in response to the occurrence of Ebola virus (subsequently identified as subtype Reston) infection among cynomolgus monkeys imported from the Philippines, the United States implemented strict disease control measures for handling nonhuman primates during transit and quarantine and initiated importer facility compliance inspections. Disease control measures emphasized protection of workers from exposure, use of containment facilities and procedures, measures to prevent spread of infection among animals, and laboratory testing of animals that die or become ill during quarantine. From 1991-1995, no outbreaks of filovirus infection occurred, and only one other disease outbreak (caused by Mycobacterium species) was recognized. In April 1996, Ebola virus (subtype Reston) infection was identified in another group of cynomolgus monkeys imported from the Philippines. The disease control measures implemented since the first Ebola virus (subtype Reston) outbreak appeared to work well. Currently, the 27 registered importer facilities import approximately 8500 nonhuman primates annually, and mortality rates are <1.0%. Importer facilities receive regular inspections, and compliance with disease control measures and disease reporting is excellent. PMID- 9988197 TI - Ebola hemorrhagic fever: lessons from Kikwit, Democratic Republic of the Congo. AB - The outbreak of Ebola hemorrhagic fever in Kikwit, Democratic Republic of the Congo, clearly signaled an end to the days when physicians and researchers could work in relative obscurity on problems of international importance, and it provided many lessons to the international public health and scientific communities. In particular, the outbreak signaled a need for stronger infectious disease surveillance and control worldwide, for improved international preparedness to provide support when similar outbreaks occur, and for accommodating the needs of the press in providing valid information. A need for more broad-based international health regulations and electronic information systems within the World Health Organization also became evident, as did the realization that there are new and more diverse partners able to rapidly respond to international outbreaks. Finally, a need for continued and coordinated Ebola research was identified, especially as concerns development of simple and valid diagnostic tests, better patient management procedures, and identification of the natural reservoir. PMID- 9988198 TI - Gleanings from the harvest: suggestions for priority actions against Ebola virus epidemics. PMID- 9988199 TI - Inner-city disadvantaged populations and asthma prevalence, morbidity, and mortality. PMID- 9988200 TI - Osteoporosis for the allergist. AB - OBJECTIVE: This review is intended to be an authoritative summary of the pathogenesis of osteoporosis, a problem that may be encountered in allergy practice. It also provides an outline for identification of subjects at high risk and directions for their appropriate evaluation, management, and prevention of the disease. DATA SOURCES: References were obtained through a MEDLINE literature search as well as from previous reviews. Relevant articles were critically reviewed and their conclusions were included. RESULTS: Osteoporosis is a relatively common disease that is associated with significant morbidity and mortality. The management and prevention of osteoporosis have been improved by an increased awareness of the magnitude of the problem, a better understanding of the pathogenesis, development of a better technique for assessment of bone mineral density, and the availability of specific medications. With the increase in human life-span and the increasing use of glucocorticosteroids for a wide variety of diseases, the incidence of osteoporosis has been on the rise. CONCLUSION: Glucocorticosteroids are the most common medications that cause or contribute to the pathogenesis of osteoporosis and have been widely used in allergy practice. It is important for physicians to appreciate the current basic understanding of osteoporosis and to be able to identify patients at high risk for this serious disorder, and to initiate appropriate intervention at a sufficiently early time to be effective. Medications for treatment and prevention of osteoporosis include: calcium, vitamin D, estrogen, bisphosphonates, calcitonin, and others are reviewed in this article. PMID- 9988201 TI - A man with multiple infections with unusual organisms. PMID- 9988202 TI - Advice from your allergist: about food allergies. PMID- 9988203 TI - Nebulized lidocaine in the treatment of severe asthma in children: a pilot study. AB - BACKGROUND: Glucocorticoids have been used to treat asthma since the 1950s; however, their adverse systemic effects have limited their duration of use and dosage. Unfortunately, many patients with severe asthma often require oral glucocorticoids in addition to inhaled glucocorticoids. Alternatives to glucocorticoids have been sought with mixed success. Recently, lidocaine has been added to the list of potent glucocorticoid sparing agents for the treatment of severe asthma. OBJECTIVE: We report the first group of pediatric patients with severe asthma treated with nebulized lidocaine. METHODS: The study was performed in an open manner with 6 severely asthmatic patients followed in the Pediatric Allergy and Immunology Section, Mayo Clinic. The only intervention was the institution of nebulized lidocaine (0.8 mg/kg/dose to 2.5 mg/kg/dose t.i.d to q.i.d). The average daily steroid requirement was followed during the administration of the nebulized lidocaine. RESULTS: During a mean of 11.2 months of therapy (range 7 to 16 months) 5 of the 6 patients completely discontinued their oral glucocorticoids within an average time of 3.4 months (range 1 to 7 months). CONCLUSIONS: After further study, lidocaine may prove to be the first non-toxic, steroid alternative to patients with severe steroid-dependent asthma. PMID- 9988204 TI - Human basophil activation measured by CD63 expression and LTC4 release in IgE mediated food allergy. AB - BACKGROUND: IgE-dependent basophil activation induced by an allergen elicit the release of LTC4 and the expression of the CD63 membrane marker. OBJECTIVE: The aim of this study was to check if flow cytometric analysis of basophil activation could be applied to food allergy diagnosis and if this method paralleled LTC4 release. METHODS: Patients were selected by the clinical history, skin tests, and provocation tests. Basophil activation induced by food extracts was studied in 24 control subjects and in 27 patients having a food allergy by LTC4 release test (LRT) and by flow cytometric anti-IgE+, CD63 + cell counting (BAT = basophil activation test). In case of negative anti-IgE response a passive blood donor basophil passive sensitization step was added to LRT and BAT. Leucocyte histamine release test was performed in 11 patients. RESULTS: Basophil activation test was positive in 18/31 cases and LRT in 22/34 cases for food-allergic patients and, respectively, in 1/33 and 1/35 cases for the controls. A correlation was observed between specific IgE, BAT, and LRT. Basophil activation test and LRT performed after passive sensitization had an excellent sensitivity only for specific IgE levels ranging between 3.5 and 35 KU/L. CONCLUSION: The present study shows that allergen-induced LTC4 release and anti-IgE, antiCD63 bicolor flow cytometric analysis of basophil activation may be used for food allergy diagnosis. Both tests have a good sensitivity and specificity. Basophil activation test and LRT are more efficient than histamine release test in case of high spontaneous histamine release, frequently observed in case of food allergy. PMID- 9988205 TI - Volumetric ragweed pollen data for eight cities in the continental United States. AB - BACKGROUND: A previous report presented volumetric ragweed pollen data for 23 cities in the continental United States. Although helpful, it did not represent all areas of the country. OBJECTIVE: The purpose of this present communication is to furnish ragweed pollen data for eight additional cities. METHODS: Ragweed pollen data were obtained from eight pollen sampling facilities in the continental United States. These data were analyzed to determine the length of the season in each city and its peak date. RESULTS: The ragweed pollen season was typically 2 or 3 months in duration. Ragweed pollen counts reached their annual maximum in late August or early September in cities in Minnesota, Nebraska, and South Dakota. The peak was achieved in late September or early October for two cities in Texas. The annual maximums for three remaining cities in Colorado, Utah and Alabama occurred in late August, early September and mid-September, respectively. CONCLUSIONS: The findings of this investigation were consistent with previous reports about the north-south nature of the ragweed pollen season. These data, when combined with the results of the 23-city investigation, indicate when source avoidance is most critical in many areas. PMID- 9988206 TI - Clinical efficacy and tolerability of a steady dosage schedule of local nasal immunotherapy. Results of preseasonal treatment in grass pollen rhinitis. AB - BACKGROUND: Local nasal immunotherapy (LNIT) is an effective and safe alternative to conventional subcutaneous immunotherapy. A specific nasal provocation test (SNPT) could be used to indicate the optimal subclinical dose to carry out LNIT. OBJECTIVE: We hypothesize that LNIT could be carried out with only one predefined dose for all patients, so we have evaluated the efficacy and the tolerability of LNIT administered at steady dosages in patients with seasonal allergic rhinitis. METHODS: Twenty grass pollen-sensitized patients suffering from seasonal allergic rhinitis were studied in a randomized, double-blind, placebo-controlled trial. The treatment was carried out according to a schedule based on the administration of a steady subclinical dosage of the allergenic extract, selected on the basis of the sensitivity threshold of the SNPT. The patients were divided into two groups of 10 people each, which were treated either with grass pollen extract in a hydroglyceric solution or with placebo. RESULTS: During the peak pollen period, with regard to the placebo (P) group, in the grass treated (GT) group a significant decrease of both nasal symptoms (P = .021) and consumption of antihistamines (P = 0.047) was found. Furthermore, only in the GT group was the provocative dose assessed by the SNPT significantly lower (P = .049) at the end of the treatment. In this group of patients an inverse correlation between such provocative dose and the nasal symptom score reported during the peak pollen period was also evidenced (r = 0.708; P = .038). Adverse reactions to LNIT were mild, rare, and did not interfere with the completion of the therapeutic schedule. CONCLUSIONS: Our study indicates that LNIT, when administered at steady dosages, may be proposed as a treatment for grass pollen seasonal allergic rhinitis as it appears to be effective and well tolerated. PMID- 9988208 TI - Nasal and bronchial histamine reactivity in patients with allergic rhinitis out of season. AB - BACKGROUND: The correlation between non-specific hyperreactivity of upper and lower airways in pathologic conditions has not been studied extensively. OBJECTIVE: To investigate the occurrence of nasal and bronchial hyperreactivity in patients with allergic rhinitis studied out-of-season. METHODS: From patients admitted to the Allergy Unit at Stockholm Soder Hospital, 12 individuals with allergic rhinitis due to grass or birch pollen were selected. The nasal mucosa was exposed to increasing concentrations of histamine chloride and the response was recorded by rhinostereometry, an optical method that exclusively measures changes in nasal congestion. Bronchial histamine challenge was performed in connection with the nasal tests, but on different days. RESULTS: The nasal histamine response was significantly greater than in a reference group of healthy volunteers (P < .01). Nasal hyperreactivity was demonstrated in 9 of 12 patients. No clear relation between the magnitude of nasal and bronchial histamine responses was seen in the study group. CONCLUSIONS: In allergic rhinitis studied out-of-season, airway hyperreactivity is common in both upper and lower airways, but does not necessarily occur together in the same individual. PMID- 9988207 TI - Anaphylaxis to omeprazole. AB - BACKGROUND: Omeprazole is a non-competitive inhibitor of the parietal cell enzyme H+-K--adenosine triphosphatase. To date, two cases of angioedema and urticaria and two cases of anaphylaxis from omeprazole have been published. OBJECTIVE: To report a new patient with omeprazole-induced anaphylaxis demonstrated by skin tests and increased serum tryptase levels. METHODS AND RESULTS: Elevated serum tryptase levels (5.1 U/L) were detected 6 hours after the onset of the anaphylaxis. Skin intradermal tests were positive with omeprazole i.v. (4 mg/mL), omeprazole capsules diluted in saline serum (20 mg/ mL), and lansoprazole (30 mg/mL). Serum specific IgE anti-omeprazole was negative. CONCLUSIONS: According to the elevated serum tryptase levels and the positive skin test results, anaphylaxis was due to use of omeprazole. We think the adverse reaction to omeprazole was induced by an IgE-mediated hypersensitivity mechanism to omeprazole itself and not to a metabolite. We have also demonstrated crossreactivity, at least by skin tests, between omeprazole and lansoprazole. PMID- 9988209 TI - An unproven technique with potentially fatal outcome: provocation/neutralization in a patient with systemic mastocytosis. AB - OBJECTIVE: To describe the risks associated with use of an unproven technique, provocation/neutralization, in diagnosis and treatment of a putative "food allergy" in a patient with systemic mastocytosis. METHODS: A case report of a 68 year-old woman with mastocytosis is reported. The patient was interviewed, examined, and all medical records were reviewed. Photos were taken, and skin and colonic biopsies were performed. RESULTS: The patient was previously diagnosed with urticaria pigmentosa but also had significant diarrhea that was well controlled by oral cromolyn sodium. She saw a physician who practiced provocation/neutralization and was told that food allergies were the cause of her gastrointestinal symptoms. She was placed on "neutralizing" injections of milk and wheat, but experienced flushing, palpitations, and lightheadedness with syncope upon injections into her thigh, which is a skin area highly involved by visible lesions of cutaneous mastocytosis. Later evaluation revealed increased numbers of mast cells in her colonic mucosa as well as confirmation of cutaneous mastocytosis. CONCLUSIONS: The patient's previous history of urticaria pigmentosa, orally communicated by the patient, documented in medical records, and easily visible on physical examination, was discounted by a practitioner of an alternative and unproven medical treatment, provocation/neutralization. She subsequently had potentially life-threatening reactions to "provocative" skin testing and "neutralizing" injections. Patients with systemic mastocytosis are at risk for significant mast cell mediator release during immunotherapy, conventional or alternative. PMID- 9988210 TI - The word "pollens" and related species. PMID- 9988212 TI - Germ cells. PMID- 9988213 TI - Mammalian fertilization: molecular aspects of gamete adhesion, exocytosis, and fusion. PMID- 9988214 TI - The sins of the fathers and mothers: genomic imprinting in mammalian development. PMID- 9988215 TI - Axis development and early asymmetry in mammals. PMID- 9988216 TI - Progression from extrinsic to intrinsic signaling in cell fate specification: a view from the nervous system. PMID- 9988217 TI - Morphogenesis. PMID- 9988218 TI - Size control in animal development. PMID- 9988219 TI - Cell death in development. PMID- 9988220 TI - Molecular development of sensory maps: representing sights and smells in the brain. PMID- 9988221 TI - Molecular bases for circadian clocks. PMID- 9988222 TI - Molecular biology of aging. PMID- 9988223 TI - Tumor-antigen heterogeneity of disseminated breast cancer cells: implications for immunotherapy of minimal residual disease. AB - Single micrometastatic tumor cells encased in mesenchymal tissues, such as bone marrow (BM), are regarded as suitable targets for adjuvant immunotherapy since they are easily accessible for both immunoglobulins and immune effector cells. However, the antigen profile of such cells, to which antibody therapy might be targeted, cannot be deduced from the antigen pattern of the primary tumor. To evaluate the antigen profile of disseminated cells found in BM aspirates from 20 breast cancer patients, we applied a quantitative immuno-cytochemical double marker assay and typed for 4 common tumor-associated cell-surface antigens (c erbB-2, CO17-1A, MUC-1, LewisY). Individual breast cancer cells were identified by F(ab) fragments of the pan-cytokeratin (CK) monoclonal antibody (MAb) A45 B/B3, directly conjugated with alkaline phosphatase, which identified cancer cells as sensitively as the standard APAAP procedure (r = 0.998; p < 0.0001). CK+ cells co-expressed c-erbB-2, CO17-1A, MUC-1 and LewisY in 87%, 78%, 79% and 79% of patients, respectively; however, the frequency of double-positive cells per sample varied considerably. The mean percentage of double-positive cells per total number of CK+ cells was 41% for c-erbB-2 (range 0-92%), 47% for CO17-1A (range 0-75%), 49% for MUC-1 (range 0-67%) and 32% for LewisY (range 0-59%). In 14 of these patients, we used an antibody cocktail to type CK+ cells for the combined expression of all 4 antigens. The antibody cocktail labeled significantly more CK+ cells than each of the single MAbs alone, resulting in a mean of 71% double-positive tumor cells (34-100%). We conclude that expression of tumor-associated cell-surface antigens on micrometastatic cancer cells in BM is heterogeneous, which may limit the efficacy of monovalent immunotherapeutic strategies directed against only one particular antigen. Thus, defining target antigens expressed by the actual target cells emerges as a crucial first step in selecting appropriate therapeutic targets. PMID- 9988224 TI - Expression of calpain I messenger RNA in human renal cell carcinoma: correlation with lymph node metastasis and histological type. AB - Calpain, also named CANP (for calcium-activated neutral protease), is an intracellular cytoplasmatic non-lysosomal cysteine endopeptidase that requires calcium ions for activity. Many substrates of the calpain isoenzymes, such as the transcription factors c-Fos and c-Jun, the tumor supressor protein p53, protein kinase C, pp60c-src and the adhesion molecule integrin, have been implicated in the pathogenesis of different human tumors, suggesting an important role of the calpains in malignant diseases. We now report differential expression of the calpain I gene (CL I) in a variety of tumors, extending our study to a larger series of renal cell carcinomas. Using Northern-blot analysis, we studied calpain I expression in 30 renal cell carcinomas as compared with matched healthy tissues. Tumor samples were classified according to their histological type: 21 clear cell carcinomas, 4 chromophobe carcinomas, 3 papillary carcinomas and 2 oncocytomas. In renal tumor samples, calpain I gene mRNA was expressed at highly variable levels, significantly depending on the different histological types. Moreover, there was a correlation of higher calpain I expression with increased malignancy: within the clear cell carcinoma subset, tumor samples with advanced nodal status (N1 and N2) showed a significantly higher calpain I expression than tumors without metastasis to regional lymph nodes. Our data suggest an important role of calpain isoenzymes in carcinogenesis and tumor progression. PMID- 9988225 TI - Levels of vascular endothelial growth factor, hepatocyte growth factor/scatter factor and basic fibroblast growth factor in human gliomas and their relation to angiogenesis. AB - Angiogenesis is a possible target in the treatment of human gliomas. To evaluate the role of 3 growth factors, vascular endothelial growth factor (VEGF), hepatocyte growth factor/scatter factor (HGF/SF) and basic fibroblast growth factor (bFGF), in the angiogenic cascade, we determined their levels in extracts of 71 gliomas by enzyme-linked immunosorbent assay (ELISA). The levels of bFGF were only marginally different between gliomas of World Health Organization (WHO) grade II (low grade) and grades III and IV (high grade). In contrast, the mean concentrations of VEGF were 11-fold higher in high-grade tumors and those of HGF/SF 7-fold, respectively. Both were highly significantly correlated with microvessel density (p < 0.001) as determined by immunostaining for factor VIII related antigen. In addition, VEGF and HGF/SF appeared to be independent predictive parameters for glioma microvessel density as determined by multiple regression analysis. We measured the capacity of all 3 factors to induce endothelial tube formation in a collagen gel. In this assay, bFGF was found to be an essential cofactor with which VEGF as well as HGF/SF were able to synergize independently. According to the concentrations of angiogenic factors, extracts from high-grade tumors were significantly more potent in the tube formation assay than the low-grade extracts (p = 0.02). Adding neutralizing antibodies to bFGF, VEGF and HGF/SF together with the extracts, tube formation was inhibited by up to 98%, 62% and 54%, respectively. Our findings suggest that bFGF is an essential cofactor for angiogenesis in gliomas, but in itself is insufficient as it is present already in the sparsely vascularized low-grade tumors. Upon induction of angiogenesis in high-grade tumors, bFGF may synergize with rising levels of not only VEGF but possibly also with HGF/SF, which appears here to be an independent angiogenic factor. PMID- 9988226 TI - BRCA1 gene mutation and loss of heterozygosity on chromosome 17q21 in primary prostate cancer. AB - The tumor suppressor gene BRCA1 on chromosome 17q21 has been characterized and shown to be mutated in patients with familial breast and ovarian cancer. Several studies examined the relatives of women with breast cancer and noted an association with ovarian and prostate cancer. This study investigated 24 human prostate cancer specimens for BRCA1 gene mutations and loss of heterozygosity (LOH) on chromosome 17q21 assessed by the polymerase chain reaction. LOH was identified using 7 highly polymorphic tandem repeat markers on chromosome 17q21, in addition to an analysis of the whole coding region of the BRCA1 gene. Four of the 24 prostate cancer specimens showed LOH at one or more loci, all of which were histologically poorly differentiated (4 of 11) and stage D (4 of 15). One of the 24 cases showed a germ-line mutation of the BRCA1 gene, and a sister of this patient died of ovarian cancer. It appears that the BRCA1 gene is not frequently involved in the development of primary prostate cancer. PMID- 9988227 TI - ErbB-4 mRNA expression is decreased in non-metastatic pancreatic cancer. AB - The erbB-4 gene encodes a detected receptor protein that possesses intrinsic tyrosine kinase activity and belongs to the family of the epidermal growth factor receptor (EGFR); erbB-4 is stimulated by the heregulins and betacellulin, which enables this receptor to form heterodimers with erbB-2, a prerequisite for erbB-2 activation. Because the expression of erbB-4 mRNA is generally low in the pancreas, quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) was used to determine the erbB-4 levels in human normal and cancerous pancreatic tissue. Our results show that the mRNA expression of this receptor is 6-fold decreased in the non-metastatic stages of pancreatic cancer when compared to tumors with lymph node or distant metastases or to the normal pancreas. In addition, immunohistochemistry demonstrated that in the normal pancreas, the erbB 4 antigen was predominantly present in the cell membrane and cytoplasm of the ductal and acinar cells and at a much lower level, in islet cells. In pancreatic cancer, 61 of 75 samples exhibited weak to moderate immunoreactivity for erbB-4 in the tumor cells. Moreover, in the peri-tumorous region with chronic pancreatitis-like morphological changes, there was weak-to-moderate erbB-4 immunostaining in small ductules and degenerating acinar cells. Uni- and multivariate survival analyses using as variables age, sex, stage of cancer, histo-pathological grading, and erbB-4 immunoreactivity, revealed a significant effect for stage of cancer (p < 0.01) whereby the risk of dying was 2.3 times higher in patients with metastases than in patients without. However, the level of erbB-4 immunoreactivity in pancreatic cancer cells had no influence on patient survival. PMID- 9988228 TI - Unchanged survival of gastric cancer in the southeastern Netherlands since 1982: result of differential trends in incidence according to Lauren type and subsite. AB - Despite widespread use of endoscopy and improved surgical treatment, the prognosis for gastric cancer remains poor. Although the incidence has been declining for more than 2 decades, unfavourable changes in relative frequency of histological subtypes and subsites may have occurred. We therefore assessed the nature and impact of these changes in association with socio-economic status in a population-based study during the period 1983-1995. Furthermore, tumour characteristics were analysed as predictors of survival for 1,543 cases recorded in the Eindhoven Cancer Registry during the period 1983-1992. Overall 5-year relative survival remained at 22%, being 70%, 37% and 11% for stage I, II and III, respectively. The Lauren histological type and location were also found to have prognostic value. Tumours with the worst prognosis (diffuse type and located at the cardia) developed predominantly in younger patients and were increasing. Moreover, unlike for other tumours, high educational status was associated with unfavourable prognosis. Stage at diagnosis and survival have remained unchanged, despite likely improvements in early detection through better access to endoscopy and better supportive care after surgical treatment. The unfavourable, in part relative, changes in incidence are likely to be responsible for the lack of improvement of survival rates. PMID- 9988229 TI - Molecular characteristics of poorly differentiated adenocarcinoma and signet-ring cell carcinoma of colorectum. AB - In a series of 45 poorly differentiated adenocarcinomas (por) and 7 signet-ring cell carcinomas (sig) of the colorectum, K-ras gene mutation, p53 immunostaining and microsatellite instability (MSI) were analyzed for a comparison with 46 cases of colorectal carcinomas of the well or moderately differentiated type (well/mod). In addition, the mutations of simple repeated sequences in the transforming-growth-factor-beta type-II receptor (T beta R-II) gene and the BAX gene were analyzed as possible targets for DNA replication errors. Mutation of the K-ras gene in the por, sig and well/mod specimens was detected in, respectively, 22%, 11% and 48%, positive immunostaining for p53 in 41.8%, 28.6% and 60.3%, and MSI in 36%, 30% and 4%. Frameshift mutation of the T beta R-II gene was detected in 27.5% of the por and none of the sig specimens, while corresponding figures for mutation of the BAX gene were 15.7% and 0%. Significant differences between the por and well/mod tumors were found in the occurrence of K ras mutation at codons 12 and 13, and MSI. Clinicopathologically, the tumor status of por with MSI was found to significantly correlate with the tumor's location in the proximal colon. In cases without MSI and sig, no frameshift mutation of either the T beta R-II or the BAX gene was found. These results suggest that poorly differentiated and signet-ring-cell carcinomas have a genetic background different from that of well or moderately differentiated carcinomas of the colorectum, and that DNA-replication error is at least partly involved in the carcinogenesis of these specific types of colorectal carcinomas. PMID- 9988230 TI - galectin-1 and galectin-3 expression in human bladder transitional-cell carcinomas. AB - Galectin-1 and galectin-3 are galactoside-binding proteins involved in different steps of tumor progression and potential targets for therapy. We have investigated the expression of these galectins in 38 human bladder transitional cell carcinomas of different histological grade and clinical stage and in 5 normal urothelium samples. Galectin-1 mRNA levels were highly increased in most high-grade tumors compared with normal bladder or low-grade tumors. Western blot and immuno-histochemical analysis of normal and neoplastic tissues revealed a higher content of galectin-1 in tumors. Galectin-3 mRNA levels were also increased in most tumors compared with normal urothelium, but levels were comparable among tumors of different histological grade. PMID- 9988231 TI - High levels of tissue inhibitor of metalloproteinase-1 predict poor outcome in patients with breast cancer. AB - Studies from model systems suggest that matrix metalloproteinases (MMPs) are causally involved in tumor progression while tissue inhibitors of MMPs (TIMPs) prevent this progression. Here, we show that concentrations of TIMP-1 are significantly higher in breast carcinomas than in fibroadenomas. In primary breast cancers, TIMP-1 concentrations increased with increasing tumor size but showed an inverse relationship with estrogen receptor concentrations. In primary breast cancers also, TIMP-1 levels were weakly but significantly correlated with those for MMP-1, proMMP-2, active MMP-2, MMP-3 and proMMP-9. Contrary to what might be expected from published data on model systems, high concentrations of TIMP-1 predicted a poor outcome in patients with breast cancer. We conclude that in human breast cancer, endogenous TIMP-1 does not inhibit tumor progression but may enhance the process. PMID- 9988232 TI - p16 inactivation in small-sized lung adenocarcinoma: its association with poor prognosis. AB - p16, an inhibitor of cell cycle machinery, is frequently inactivated in non-small cell carcinoma of the lung (NSCCL). To clarify the significance of p16 inactivation in the progression of lung adenocarcinoma, we immunohistochemically evaluated p16 protein status and Rb, p53 and cyclin D1 expression in 51 surgically resected adenocarcinomas that were less than 3 cm in diameter (median follow-up period: 52.5 months). Twenty-one of 51 adenocarcinomas showed negative immunostaining for p16. Twenty adenocarcinomas were also negative for Rb, while 31 and 13 were positive for p53 and cyclin D1, respectively. Loss of p16 expression was significantly correlated with scar grade, lymphatic permeation, lymph node metastasis and clinical stage. Rb protein expression was also inversely correlated with scar grade, pleural involvement and vascular invasion. When the cases were stratified according to the expression of both proteins, the Rb-/p16- subset (7/51) consisted of poorly differentiated adenocarcinoma with a higher grade of invasion. While Rb, p53 and cyclin D1 protein status showed no significant correlations with prognosis, p16 inactivation was significantly correlated with poor prognosis, and the prognosis of Rb-/p16- was the worst among the 4 subsets. Inactivation of p16 may play a role in accelerating scar formation and lymph node metastasis, and may contribute through these mechanisms to poor prognosis in patients with small-sized lung adenocarcinoma. PMID- 9988233 TI - Endocrine response and resistance in breast cancer: a role for the transcription factor Fos. AB - We have previously demonstrated that elevated Fos expression may be important in de novo endocrine resistance in breast cancer. However, changes in Fos expression during endocrine response and subsequently on acquisition of resistance are unknown. This study immunocytochemically monitors Fos protein within sequential biopsies from primary human breast cancer patients obtained pre-treatment (T1), during tamoxifen therapy (T2, T3) and on disease progression (T5), examining in parallel proliferation [i.e., MIBI (Ki67) immunostaining, mitotic activity], cellularity and endocrine response. Significantly diminished Fos, proliferation and cellularity were observed after 6 weeks of therapy in patients exhibiting a better quality and/or duration of response, while modest Fos increases and a maintained proliferation and cellularity were seen in poorer responders. Decreases in Fos, proliferation and cellularity at 6 months similarly hallmarked better responders. We confirmed a significant association between de novo resistance and elevated Fos and proliferation. Additionally, however, these parameters increased at the time of disease relapse over pre-treatment and "on therapy" values. Our data indicate that tamoxifen response involves a reduction in both tumor cell proliferation and cell survival, potentially entailing diminished Fos protein expression in better-responding patients. Our data are also supportive of elevated Fos expression being involved in the departure from endocrine control inherent in both primary and acquired resistance. PMID- 9988234 TI - Level of anti-mouse-antibody response induced by bi-specific monoclonal antibody OC/TR in ovarian-carcinoma patients is associated with longer survival. AB - More than 60% of cancer patients injected with intact murine monoclonal antibody (MAb) develop a humoral response against the antigen even after a single dose. Analysis of a series of 35 ovarian-cancer patients entered in phase-I and -II clinical studies of T-cells retargeted with the bi-specific F(ab')2 OC/TR revealed: (i) a detectable human anti-mouse antibody (HAMA) response in 31/35 (88%) patients, with high HAMA levels (> or = 150 ng/ml) in 18/31 (58%) cases by the end of the treatment; (ii) no correlation between HAMA levels and the form of delivery of the mAb (OC/TR bound to T cells or bound plus soluble), time schedule or cumulative dose; (iii) an association between high HAMA levels and favorable clinical parameters and response to immunotherapy; and (iv) a significantly longer median survival probability in patients with high HAMA levels than in patients with lower HAMA levels, even when the sub-group of non-responder patients was considered. Evaluation of the anti-idiotypic response in HAMA positive sera indicated that 11/17 sera showed high-titer (>6000) binding of OC/TR, as evaluated by a specific radioimmunoassay, and 15/18 and 16/16 sera specifically inhibited the binding of the MOv18 and anti-CD3 parental MAbs to ovarian-carcinoma cells and T lymphocytes respectively. Of 7 patients evaluated for duration of the HAMA response, 5 showed stable or even increased HAMA levels. The long-lasting HAMA response maintained an anti-idiotypic component, directed mainly against the alphaCD3 idiotype of bi-MAb OC/TR in 2 out of 3 cases tested. PMID- 9988235 TI - Integrated approach to prediction of cervical intra-epithelial neoplasia status through a case-control study. AB - A case-control study on cervical intra-epithelial neoplasia (CIN) was carried out on 398 subjects in the state of West Bengal, India. These samples were taken from mass screening programs organized by the authors, maintaining the uniformity of sampling to the extent possible. The cervical smears were tested by the Papanicolaou (PAP) method, following the Bethesda system for reporting of CIN status. Odds ratios and correlation coefficients among different variables, assumed to produce carcinoma of the cervix, show that 6 out of 11 variables, i.e., age, education, socio-economic status, duration of marriage, age at marriage and body surface, are associated with CIN. Multivariate analysis of logistic regression was carried out using BMDP-LR with dichotomized response variables considering CIN (0 and 1) in one group and CIN (2 and 3) in the other group. The outcome of the analysis indicated that age and educational level are 2 contributing factors for CIN. The percentage of correct classification in this analysis has improved to 74.5%, with a probability of 0.90. Polychotomous regression analysis was carried out using BMDP-PR in the next step. This analysis showed that parity was a contributing factor, in addition to age and educational level. These 3 factors provide a predictive model for identifying the high-risk group in a rational way. This approach would restrict screening to approximately 10% of the population. Subsequently, the model has been validated in a confirmatory trial among 85 new cases and was found to work satisfactorily. PMID- 9988236 TI - Differing expression of MMPs-1 and -9 and urokinase receptor between diffuse- and intestinal-type gastric carcinoma. AB - Gastric cancer is classified into intestinal and diffuse types, which exhibit different biological behavior. Urokinase-type plasminogen activator (uPA), its receptor (uPAR) and matrix metalloproteinases (MMPs)-1 and -9 are considered to play important roles in cancer invasion and metastasis. We have already suggested a functional duality of these matrix-degrading enzymes/factors; they may also be involved in the matrix turnover (remodeling) or host immune/inflammatory reactions as far as they are expressed by host cells. We performed a retrospective study on the immuno-histochemical expression of these enzymes/factors in surgical specimens from patients with gastric cancer, including 26 with the diffuse and 78 with the intestinal type. We also evaluated macrophages since they are major sources of uPAR. The positivity rate for uPA in cancer cells was significantly lower in diffuse-type than in intestinal-type. Stromal expression was seen mainly along the invasive margin (tumor-host interface). The degree of stromal expression of uPAR and MMP-9 and the macrophage number were markedly decreased in diffuse-type compared with intestinal-type. Stromal expression of uPAR and macrophage number in intestinal-type were higher in patients without liver metastasis than in patients with liver metastasis, while uPA expression in cancer cells was more pronounced in patients with liver metastasis. Studies using frozen sections revealed that the expression of MMP-1, restricted to the stromal area, was more decreased in diffuse-type (18 patients) than in intestinal-type (21 patients). Our results show that the in situ expression of matrix-degrading enzymes/factors in gastric cancer is significantly more diminished in diffuse-type than in intestinal-type, suggesting a multifunctional aspect of the matrix-degradation process in cancer tissue. PMID- 9988237 TI - P-glycoprotein is positively correlated with p53 in human oral pre-malignant and malignant lesions and is associated with poor prognosis. AB - P-glycoprotein (Pgp) encoded by the MDR1 gene, a predictor of chemoresistance, may also serve as a prognosticator of clinical outcome in cancer patients. The mutant tumour-suppressor p53 protein has been shown to activate the MDR1 promoter, whereas the wild-type p53 represses this activity in cultured cells. We have described the differential expression of Pgp and p53 proteins in betel- and tobacco-related oral tumorigenesis in the Indian population. Herein, Pgp expression was analysed in relation to p53 protein accumulation in pre-malignant and malignant oral lesions by immunohistochemical and flow-cytometric analyses. The relationship between Pgp and p53 protein accumulation and clinicopathological parameters as well as prognosis was determined. Expression of Pgp was observed in 81% of oral squamous cell carcinomas (SCCs) and 71% of pre-malignant lesions. Sixty-five of 75 p53-positive oral SCCs and 21/24 p53-positive pre-malignant lesions showed expression of Pgp. Significant correlation between Pgp and p53 expression was found not only in oral SCCs but also in pre-malignant lesions. Co expression of Pgp and p53 proteins was indicative of poor prognosis. Follow-up studies of 35 patients showed that 7 of 10 oral SCCs with accumulation of Pgp and p53 proteins also exhibited shorter disease-free survival (recurrence/metastases). Our findings provide clinical evidence for a significant association between Pgp and p53 protein expression in oral tumorigenesis and may account for the aggressive nature of the tumour and poor prognosis. PMID- 9988238 TI - Prognostic significance of cyclin D1 in esophageal squamous cell carcinoma patients treated with surgery alone or combined therapy modalities. AB - In the present study, the expression of cyclin D1, as detected by immunohistochemistry, was compared with other prognostic variables and its prognostic impact was evaluated in a group of 172 patients with squamous cell carcinoma (SCC) of the esophagus who underwent potentially curative resection therapy and in a second group of 38 patients with SCC of the esophagus who were treated by combined modality therapy (radiochemotherapy +/- surgery). Expression of cyclin D1 in surgically treated carcinomas correlated negatively with tumor differentiation (p = 0.026) but positively with mitotic activity (p = 0.0199) and nodal status (p = 0.040). There were no significant correlations with pT category. Patients with cyclin D1-positive carcinomas showed significantly worse overall survival than patients with cyclin D1-negative carcinomas, both in univariate (p = 0.0016) and in multivariate survival analyses (p = 0.0038). Expression of cyclin D1 in carcinomas with multimodal treatment was correlated with poor response to chemotherapy (p = 0.026) but not with overall survival. We thus consider expression of cyclin D1 to be an important parameter, predicting an unfavorable overall survival of surgically treated esophageal cancer patients. PMID- 9988239 TI - Amplified DNA testing for sexually transmitted diseases: new opportunities and new questions. PMID- 9988240 TI - The art of precepting: Socrates or Aunt Minnie? PMID- 9988241 TI - Is the routine pelvic examination needed with the advent of urine-based screening for sexually transmitted diseases? AB - OBJECTIVE: To determine the most cost-effective method of screening for chlamydia and gonorrhea to prevent pelvic inflammatory disease (PID) in asymptomatic sexually active adolescent females. DESIGN: Cost-effectiveness decision analysis comparing pelvic examination with cervical screening (the current national standard) with a model of urine screening with ligase chain reaction testing for Chlamydia trachomatis and Neisseria gonorrhoeae. METHODS: Four strategies using decision analysis were compared for a potential cohort of 100000 asymptomatic sexually active young women: (1) pelvic examination screening in 100%; (2) urine screening in 100%; (3) actual predicted pelvic examination screening in 70%; and (4) actual predicted urine screening in 90%. Assumptions and costs were generated from published sources. MAIN OUTCOME MEASURES: Cases of PID prevented per year and cost to prevent a case of PID. RESULTS: A total of 1750 cases of PID would be predicted to occur per year with no screening. Strategy 1 would prevent the most cases of PID (1283) at a mean cost of $10230. Strategy 2 would prevent 1215 cases of PID at a mean cost of $5093. The marginal cost to prevent an additional case of PID by strategy 1 is $101454. Strategy 3 would prevent 898 cases of PID and 1093 cases of PID would be prevented with urine screening in strategy 4. CONCLUSION: Urine-based ligase chain reaction screening is the most cost effective strategy to detect chlamydial and gonococcal genital infection in asymptomatic sexually active adolescent females and, owing to ease of implementation, the most likely to prevent the greatest number of cases of PID. PMID- 9988242 TI - Clinical and economic impact of a combination Haemophilus influenzae and Hepatitis B vaccine: estimating cost-effectiveness using decision analysis. AB - BACKGROUND: Compliance with hepatitis B virus (HBV) vaccine remains suboptimal, despite a recommendation by the Advisory Committee on Immunization Practices of the US Public Health Service that all newborns be vaccinated. Although a combined HBV-Haemophilus influenzae type b (Hib) vaccine may improve acceptance of the HBV vaccine, the clinical and economic consequences of this intervention are uncertain. OBJECTIVES: To compare the health impact and cost-effectiveness of the following 2 immunization strategies: current practice of administering HBV vaccine separately (75% compliance) and Hib vaccine alone or as part of a multivalent vaccine (95% compliance); and strategy of delivering a combined HBV Hib vaccine (95% compliance). DESIGN: A Markov model simulated the natural history of acute and chronic HBV and Hib disease in a cohort of US newborns. Clinical and economic variables were obtained from published reports. RESULTS: The Hib-related outcomes were the same in both strategies, because the efficacy and compliance with Hib vaccine were assumed to be equivalent in both. A 53% reduction in the number of cases of HBV infection with the combination strategy (n = 8541) was estimated when compared with current practice (n = 18 044), along with 205 fewer HBV-related deaths per 1 million infants. Immunization costs of the combination strategy were $11.5 million higher than for current practice ($108.4 million compared with $96.9 million), whereas the cost of HBV-related disease was $4.0 million lower than in current practice. The incremental cost effectiveness ratio for the combination strategy was $17700 per year of life saved. CONCLUSION: An HBV-Hib vaccine in US infants yields substantial benefits, with a cost-effectiveness ratio that is lower than that of many commonly used medical interventions. PMID- 9988243 TI - Biopsychological and cognitive differences in children with premature vs. on-time adrenarche. AB - BACKGROUND: Puberty consists of 2 components: gonadarche and adrenarche. Both components have distinct endocrine changes. Adrenarche has virtually been ignored with respect to examining hormone-behavior relations. OBJECTIVES: To provide descriptive biological and behavioral information on children with premature adrenarche (PA) and to examine differences in biological, psychological, and cognitive variables of children with PA and a healthy comparison group of children with on-time adrenarche. DESIGN: Descriptive pilot study. SETTING: A consecutive sample of patients was recruited from pediatric endocrine clinics; comparison children were recruited from the community. PARTICIPANTS: Children aged 6 to 9 years. Mean (+/-SD) age of children with PA (n = 9) was 7.8 (+/-1.3) years; of children with on-time adrenarche (n = 20), 8.0 (+/-1.2) years. METHODS AND MEASURES: Serum and saliva samples were collected for measurement of hormone concentrations. Questionnaires, tests, and interviews were completed by children and parents. RESULTS: Compared with the on-time group, the PA group had significantly higher concentrations of adrenal androgens, estradiol, thyrotropin, and cortisol. By parent report on the Diagnostic Interview Schedule for Children, 4 children (44%) met diagnostic criteria for psychological disorders (primarily anxiety disorders). The PA group also had more self-reported depression and parent-reported behavior problems and lower scores on various intelligence tests. CONCLUSIONS: Although PA is considered a normal variation of pubertal development that warrants no medical intervention, PA presents with significant psychosocial problems. Children with PA may need psychological evaluation and follow-up. Future studies should confirm these findings with a larger sample and examine the long-term ramifications of this early presenting abnormality. PMID- 9988244 TI - Testing the epidemiologic paradox of low birth weight in Latinos. AB - BACKGROUND: Rates of low-birth-weight (LBW) infants are similar between Latina and white women, an epidemiologic paradox. However, few studies have analyzed the relationship between ethnicity, Latino subgroup, confounding variables, and LBW. METHODS: We analyzed 395070 singleton livebirths to Latina and non-Latina white women in California during 1992. Multivariate logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the risks due to Latino ethnicity and Latino subgroup for very LBW (VLBW, 500-1499 g) and moderately LBW (MLBW, 1500-2499 g) outcomes. RESULTS: Latina and white women had similar unadjusted rates of VLBW (0.7% vs. 0.6%) and MLBW infants (3.7% vs. 3.4%). After adjusting for maternal age, education, birthplace, marital status, parity, tobacco use, use of prenatal care, infant sex, and gestational age, there was no difference in the odds of VLBW infants between Latina and white women (OR, 0.93 [95% CI, 0.81-1.071). Latina women had minimally elevated odds of MLBW infants (OR, 1.06 [95% CI, 1.01-1.11]) compared with white women. By Latino subgroup, there was no difference in the adjusted odds of VLBW infants among Central and South American, Cuban, Mexican, Puerto Rican, and white women. The adjusted odds of MLBW infants were elevated among Central and South American (OR, 1.14 [95% CI, 1.05-1.25]) and Puerto Rican women (OR, 1.41 [95% CI, 1.12-1.78]), relative to white women. CONCLUSIONS: The epidemiologic paradox of LBW in Latinos is valid. New conceptual models are needed to identify Latina women who are at risk for adverse pregnancy outcomes. PMID- 9988245 TI - Interview strategies commonly used by pediatricians. AB - OBJECTIVES: To describe the pediatric interview as it is conducted in different practice settings and with children ranging in age from infancy to adolescence, and to identify pediatric history-taking strategies that varied across age groups. PARTICIPANTS AND METHODS: A self-administered survey was designed and mailed to a group of pediatricians in the Chicago metropolitan area to assess commonly used strategies in the pediatric interview across varied patient ages and settings. The pediatricians sampled varied by geographic location as well as by practice setting. RESULTS: Results of the survey indicated that pediatricians use common strategies for establishing rapport, calming the disruptive child, and obtaining information from the child within particular age groups, but vary these strategies as the child matures. CONCLUSIONS: The findings substantiate the influence of the developmental stage of the child on interview strategies used by pediatricians. Implications pertaining to development of a standardized teaching curriculum for the pediatric interview are also discussed. PMID- 9988246 TI - Exposure to drug trafficking among urban, low-income African American children and adolescents. AB - OBJECTIVE: To examine the association between exposure to drug trafficking (selling or delivering drugs) and exposure to other forms of community violence and risk behaviors among urban, low-income African American children and adolescents. DESIGN: Community-based, cross-sectional survey. SETTING: Ten public housing developments in a large eastern city in the United States. PARTICIPANTS: Three hundred forty-nine urban, low-income African American children and adolescents (198 boys and 151 girls), aged 9 to 15 years. MAIN OUTCOME MEASURES: Exposure to drug trafficking and other forms of community violence (as either a victim or a witness), risk behaviors/perceptions including risk taking/delinquency, drug use, perpetration of violence or other crimes, threats to school achievement, and perceived peer involvement. ANALYSIS: Exploratory factor analysis was performed to examine whether exposure to drug trafficking is a risk factor that is distinct from other exposure to violence. Multivariate analysis of variance and chi2 tests were performed to assess the relationship between exposure to drug trafficking and other forms of community violence and risk behaviors/perceptions. RESULTS: Of 349 participants, 63 (18%) had been asked to traffic drugs and 134 (38%) had seen someone else being asked to traffic drugs. Factor analysis indicates that exposure to drug trafficking appears to be different from other forms of community violence. However, having been asked and having seen other people being asked to traffic drugs were both strongly associated with exposure to other forms of community violence. Compared with children and adolescents who had not been exposed to drug trafficking, those who were exposed to drug trafficking reported more risk-taking and delinquent behaviors, drug use, threats to achievement, and a perception of more peer involvement in these risk behaviors. CONCLUSION: Exposure to drug trafficking is a unique risk factor that is strongly associated with exposure to other forms of community violence and involvement in other risk behaviors. PMID- 9988247 TI - The influence of chronic disease on resource utilization in common acute pediatric conditions. Financial concerns for children's hospitals. AB - OBJECTIVES: To estimate the resource utilization in hospitalizations for common pediatric conditions or procedures involving patients with chronic disease vs those with no chronic disease and to develop an economic model of hospital per patient profit (or loss) when insurance contracts fail to account for the presence of chronic disease. SETTING AND DESIGN: A retrospective analysis of selected acute pediatric conditions found in the 1991 and 1992 MedisGroups National Comparative Data Base. PATIENTS: We studied 30379 pediatric admissions for common acute conditions, including concussion, croup, pneumonia, appendicitis, gastroenteritis, fractures, cellulitis, urinary tract infection, and viral illness. MAIN OUTCOME MEASURES: Hospital length of stay and total hospital charges. RESULTS: For patients without chronic disease, mean (geometric) length of stay was 2.53 vs. 3.05 days (P<.001) for patients with at least 1 chronic disease. For patients without chronic disease, mean (arithmetic) total hospital charge was S2614 vs. $3663 (P<.001) for patients with at least 1 chronic disease. Assuming 75% of patients with chronic disease are admitted to a children's hospital vs 25% to a general hospital, overall loss per patient at the children's hospital ranged between 1.5% and 2.9%, depending on assumptions regarding cost-to-charge ratios and the treatment of charge outliers. Pneumonia cases were associated with a 4.0% to 5.85% loss. CONCLUSIONS: Length of stay and charges are higher for everyday pediatric conditions or procedures when patients also have a chronic disease. If insurance contracts fail to account for chronic disease, then children's hospitals will realize significant financial losses, and over time this will lead to a decline in their financial viability, a reduction in quality, or a change in their mission. PMID- 9988248 TI - Beach week: a high school graduation rite of passage for sun, sand, suds, and sex. AB - BACKGROUND: Every year, thousands of suburban high school graduates from mid Atlantic states flock to nearby coastal beaches for a long-anticipated rite of passage known as "beach week." Sand, sun, and sea, and also smoking, binge drinking, drugs, and sex, are reported to be dominant themes. OBJECTIVE: To document risk-taking behaviors by girls during beach week. METHOD: Fifty-nine female suburban high school graduates who attended beach week in 1996 volunteered to fill out a confidential printed survey. Twenty-five girls (42%) completed the survey during a typical beach week party. Their activities were verified on site by a peer, recommended by her grade advisor for her integrity and popularity. Breath alcohol values were obtained at entry and departure from the party. The remaining 34 girls completed the supervised survey 2 to 3 months later. RESULTS: Daily cigarette smoking (54%), daily drunkenness (75%), and sex (46%) were the norm among respondents of our survey. Few reported first-time sex (n = 4) or drug use (n = 2). Abstinence from drugs (67%) and sex (55%) was not unusual but only 12% abstained from getting drunk. Sixteen girls (64%) reported that they drank 8 or more beers/wine during a typical beach week party. By departure from the party, 15 girls had breath alcohol values of 0.017 mmol/L or greater (reference range, <21.7 mmol/L), and 8 additional girls had breath alcohol values of 0.01 mmol/L to 0.015 mmol/L. Fifteen percent of the 59 reported injuries or illness were related to alcohol or drugs. CONCLUSION: Most respondents enjoyed beach week but a large percentage engaged in serious risk-taking behaviors. PMID- 9988250 TI - Development of feeding practices during the first 5 years of life. AB - OBJECTIVE: To understand the transition from breast-and bottle-feeding to solid feeding and factors that might affect the duration of breast- and bottle-feeding. DESIGN: Cohort followed up from birth with relatively well-educated, middle-class parents. SETTING: Community sample recruited from 3 suburban newborn nurseries (a teaching hospital, community hospital, and large health maintenance organization). PARTICIPANTS: One hundred ninety-one healthy full-term infants. MEASURES: Assessment of feeding practices through the ages of complete weaning from breast- and bottle-feeding. RESULTS: More than 90% of participants breast fed for at least 2 weeks. Infants of older mothers were weaned from the breast later than infants of younger mothers. First-born infants were weaned from the breast earlier than later-born infants. Eighty-four percent of infants bottle-fed at some time during the first year of life. More than 40% of the cohort was still receiving bottles at 24 months of age, 16% at 36 months, and 8% at 48 months. The duration of breast- and bottle-feeding was related to maternal work status; mothers who returned to work during the first 3 months postpartum weaned sooner from the breast and later from the bottle than women who returned to work after 3 months postpartum. CONCLUSIONS: The frequency of late bottle-weaning in this well educated, middle-class cohort was unexpected and was related to the timing of the mother's return to work. The impact of prolonged bottle-feeding on later growth and adiposity deserves further investigation. PMID- 9988249 TI - Neonatal jaundice and diet. AB - OBJECTIVE: To determine whether an earlier observation, that infants fed a casein hydrolysate formula (Nutramigen) have lower neonatal jaundice levels than those fed standard formulas, would be repeated in a larger independent group of infants with more frequent measurements and more rigorous statistical analysis. DESIGN: Newborn infants were fed human milk, a standard whey-predominant formula (Enfamil), or Nutramigen (n = 20 for each group) during the first 3 weeks of life. Transcutaneous jaundice index was measured daily for the first week of life and every 2 to 3 days thereafter, using a noninvasive jaundice meter. Linear regression models of the data were constructed, validated, and compared statistically. SETTING: General community hospital with subsequent home visitation. PARTICIPANTS: Healthy, term newborn infants selected by convenience, based on time of birth. INTERVENTION: Infants were exclusively fed human milk, Enfamil, or Nutramigen. Formulas were randomly assigned. MAIN OUTCOME MEASURE: Jaundice index, a transcutaneous measurement of jaundice. RESULTS: The jaundice index differed significantly among the 3 groups. Paired comparisons showed that the jaundice index of the Nutramigen group was significantly lower than that of the Enfamil group (on days 6-16) and the human milk group (on days 3-20). The jaundice index of the Enfamil-fed group was significantly lower than that of the human milk group on days 13 to 19. CONCLUSIONS: Jaundice levels are lower in neonates fed Nutramigen rather than Enfamil and both these groups have lower jaundice levels than breast-fed infants. PMID- 9988251 TI - Successful teaching of pediatric fluid management using computer methods. AB - OBJECTIVES: To identify and measure differences in knowledge of pediatric fluid management procedures between students taught by computer tutorial and others taught by lecture or seminar. DESIGN: Cohort analytic study. SETTING: Two community-based medical school pediatric teaching services. PARTICIPANTS: Eighty nine third-year medical students with no prior pediatric fluid management experience. INTERVENTIONS: Forty-eight students at one community campus completed a microcomputer-based tutorial program that replaced all teaching sessions in pediatric fluid management. Forty-one students from a similar community campus were taught identical content by a pediatric critical care specialist using a seminar, reading material, and handouts. MAIN OUTCOME MEASURES: Scores on 2 free answer problems on treatment of a dehydrated child, which were graded by a single evaluator blinded to the teaching method used, and scores on a 20-item multiple choice examination. RESULTS: The computer instruction group achieved significantly higher test scores than the seminar group for both the multiple choice examination (81.1% vs 62.2%; P<.001) and the free-answer test (85.4% vs. 61.0%; P<.001). CONCLUSIONS: The computer tutorial in fluid therapy has been an effective means of meeting the defined objectives of the pediatric clerkship. Compared with traditional methods, students taught using the computer achieved significantly higher scores on tests of both factual knowledge and practical problem solving. PMID- 9988252 TI - Radiological case of the month. Necrotizing enterocolitis in a term infant. PMID- 9988253 TI - Picture of the month. Trichophyton verrucosum tinea corporis. PMID- 9988254 TI - Pathological case of the month. Synovial lipomatosis. PMID- 9988255 TI - Mycotoxins and pulmonary hemorrhage. PMID- 9988257 TI - Patenting ESTs: is it worth it? PMID- 9988256 TI - Studying inner-city achievers. PMID- 9988258 TI - You don't need a backbone to carry a tumour suppressor gene. PMID- 9988259 TI - Less from more: cosuppression of transposable elements. PMID- 9988260 TI - Extracellular matrix calcification: where is the action? PMID- 9988261 TI - Forever hopeful relations: chromatin, telomeres and checkpoints. PMID- 9988262 TI - An imprinted QTL with major effect on muscle mass and fat deposition maps to the IGF2 locus in pigs. PMID- 9988263 TI - A paternally expressed QTL affecting skeletal and cardiac muscle mass in pigs maps to the IGF2 locus. PMID- 9988264 TI - QTL influencing autoimmune diabetes and encephalomyelitis map to a 0.15-cM region containing Il2. PMID- 9988265 TI - Late onset of renal and hepatic cysts in Pkd1-targeted heterozygotes. PMID- 9988266 TI - Cancer epigenetics comes of age. AB - The discovery of numerous hypermethylated promoters of tumour-suppressor genes, along with a better understanding of gene-silencing mechanisms, has moved DNA methylation from obscurity to recognition as an alternative mechanism of tumour suppressor inactivation in cancer. Epigenetic events can also facilitate genetic damage, as illustrated by the increased mutagenicity of 5-methylcytosine and the silencing of the MLH1 mismatch repair gene by DNA methylation in colorectal tumours. We review here current mechanistic understanding of the role of DNA methylation in malignant transformation, and suggest Knudson's two-hit hypothesis should now be expanded to include epigenetic mechanisms of gene inactivation. PMID- 9988267 TI - The gene encoding ribosomal protein S19 is mutated in Diamond-Blackfan anaemia. AB - Diamond-Blackfan anaemia (DBA) is a constitutional erythroblastopenia characterized by absent or decreased erythroid precursors. The disease, previously mapped to human chromosome 19q13, is frequently associated with a variety of malformations. To identify the gene involved in DBA, we cloned the chromosome 19q13 breakpoint in a patient with a reciprocal X;19 chromosome translocation. The breakpoint occurred in the gene encoding ribosomal protein S19. Furthermore, we identified mutations in RPS19 in 10 of 40 unrelated DBA patients, including nonsense, frameshift, splice site and missense mutations, as well as two intragenic deletions. These mutations are associated with clinical features that suggest a function for RPS19 in erythropoiesis and embryogenesis. PMID- 9988268 TI - Human homologue of the Drosophila melanogaster lats tumour suppressor modulates CDC2 activity. AB - We have previously used mosaic flies to screen for tumour suppressors or negative regulators of cell proliferation. The cellular composition of these flies resembles that of cancer patients who are chimaeric individuals carrying a small number of mutated somatic cells. One of the genes we identified is the large tumour suppressor gene, lats (also known as wts), which encodes a putative serine/threonine kinase. Somatic cells mutant for lats undergo extensive proliferation and form large tumours in many tissues in mosaic adults. Homozygous mutants for various lats alleles display a range of developmental defects including embryonic lethality. Although many tumour suppressors have been identified in Drosophila melanogaster, it is not clear whether these fly genes are directly relevant to tumorigenesis in mammals. Here, we have isolated mammalian homologues of Drosophila lats. Human LATS1 suppresses tumour growth and rescues all developmental defects, including embryonic lethality in flies. In mammalian cells, LATS1 is phosphorylated in a cell-cycle-dependent manner and complexes with CDC2 in early mitosis. LATS1-associated CDC2 has no mitotic cyclin partner and no kinase activity for histone H1. Furthermore, lats mutant cells in Drosophila abnormally accumulate cyclin A. These biochemical observations indicate that LATS is a novel negative regulator of CDC2/cyclin A, a finding supported by genetic data in Drosophila demonstrating that lats specifically interacts with cdc2 and cyclin A. PMID- 9988269 TI - Mice deficient of Lats1 develop soft-tissue sarcomas, ovarian tumours and pituitary dysfunction. AB - The lats gene has been identified as a tumour suppressor in Drosophila melanogaster using mosaic screens. Mosaic flies carrying somatic cells that are mutant for lats develop large tumours in many organs. The human LATS1 homologue rescues embryonic lethality and inhibits tumour growth in lats mutant flies, demonstrating the functional conservation of this gene. Biochemical and genetic analyses have revealed that LATS1 functions as a negative regulator of CDC2 (ref. 3). These data suggest that mammalian LATS1 may have a role in tumorigenesis. To elucidate the function of mammalian LATS1, we have generated Lats1-/- mice. Lats1 /- animals exhibit a lack of mammary gland development, infertility and growth retardation. Accompanying these defects are hyperplastic changes in the pituitary and decreased serum hormone levels. The reproductive hormone defects of Lats1-/- mice are reminiscent of isolated LH-hypogonadotropic hypogonadism and corpus luteum insufficiency in humans. Furthermore, Lats1-/- mice develop soft-tissue sarcomas and ovarian stromal cell tumours and are highly sensitive to carcinogenic treatments. Our data demonstrate a role for Lats1 in mammalian tumorigenesis and specific endocrine dysfunction. PMID- 9988270 TI - Activating SRC mutation in a subset of advanced human colon cancers. AB - The discovery of Rous sarcoma virus (RSV) led to the identification of cellular Src (c-Src), a non-receptor tyrosine kinase, which has since been implicated in the development of numerous human cancers. c-Src has been found to be highly activated in colon cancers, particularly in those metastatic to the liver. Studies of the mechanism of c-Src regulation have suggested that c-Src kinase activity is downregulated by phosphorylation of a critical carboxy-terminal tyrosine (Tyr 530 in human c-Src, equivalent to Tyr 527 in chicken Src) and have implied the existence of activating mutations in this C-terminal regulatory region. We report here the identification of a truncating mutation in SRC at codon 531 in 12% of cases of advanced human colon cancer tested and demonstrate that the mutation is activating, transforming, tumorigenic and promotes metastasis. These results provide, for the first time, genetic evidence that activating SRC mutations may have a role in the malignant progression of human colon cancer. PMID- 9988271 TI - An encyclopedia of mouse genes. AB - The laboratory mouse is the premier model system for studies of mammalian development due to the powerful classical genetic analysis possible (see also the Jackson Laboratory web site, http://www.jax.org/) and the ever-expanding collection of molecular tools. To enhance the utility of the mouse system, we initiated a program to generate a large database of expressed sequence tags (ESTs) that can provide rapid access to genes. Of particular significance was the possibility that cDNA libraries could be prepared from very early stages of development, a situation unrealized in human EST projects. We report here the development of a comprehensive database of ESTs for the mouse. The project, initiated in March 1996, has focused on 5' end sequences from directionally cloned, oligo-dT primed cDNA libraries. As of 23 October 1998, 352,040 sequences had been generated, annotated and deposited in dbEST, where they comprised 93% of the total ESTs available for mouse. EST data are versatile and have been applied to gene identification, comparative sequence analysis, comparative gene mapping and candidate disease gene identification, genome sequence annotation, microarray development and the development of gene-based map resources. PMID- 9988272 TI - Hephaestin, a ceruloplasmin homologue implicated in intestinal iron transport, is defective in the sla mouse. AB - Iron is essential for many cellular functions; consequently, disturbances of iron homeostasis, leading to either iron deficiency or iron overload, can have significant clinical consequences. Despite the clinical prevalence of these disorders, the mechanism by which dietary iron is absorbed into the body is poorly understood. We have identified a key component in intestinal iron transport by study of the sex-linked anaemia (sla) mouse, which has a block in intestinal iron transport. Mice carrying the sla mutation develop moderate to severe microcytic hypochromic anaemia. Although these mice take up iron from the intestinal lumen into mature epithelial cells normally, the subsequent exit of iron into the circulation is diminished. As a result, iron accumulates in enterocytes and is lost during turnover of the intestinal epithelium. Biochemical studies have failed to identify the underlying difference between sla and normal mice, therefore, we used a genetic approach to identify the gene mutant in sla mice. We describe here a novel gene, Heph, encoding a transmembrane-bound ceruloplasmin homologue that is mutant in the sla mouse and highly expressed in intestine. We suggest that the hephaestin protein is a multicopper ferroxidase necessary for iron egress from intestinal enterocytes into the circulation and that it is an important link between copper and iron metabolism in mammals. PMID- 9988273 TI - Prolongation of ovarian lifespan into advanced chronological age by Bax deficiency. AB - Female mammals are endowed with a finite number of oocytes at birth, each enclosed by a single layer of somatic (granulosa) cells in a primordial follicle. The fate of most follicles is atretic degeneration, a process that culminates in near exhaustion of the oocyte reserve at approximately the fifth decade of life in women, leading to menopause. Apoptosis has a fundamental role in follicular atresia, and recent studies have shown that Bax, which is expressed in both granulosa cells and oocytes, may be central to ovarian cell death. Here we show that young adult female Bax-/- mice possess threefold more primordial follicles in their ovarian reserve than their wild-type sisters, and this surfeit of follicles is maintained in advanced chronological age, such that 20-22-month-old female Bax-/- mice possess hundreds of follicles at all developmental stages and exhibit ovarian steroid-driven uterine hypertrophy. These observations contrast with the ovarian and uterine atrophy seen in aged wild-type female mice. Aged female Bax-/- mice fail to become pregnant when housed with young adult males; however, metaphase II oocytes can be retrieved from, and corpora lutea form in, ovaries of aged Bax-/- females following superovulation with exogenous gonadotropins, and some oocytes are competent for in vitro fertilization and early embryogenesis. Therefore, ovarian lifespan can be extended by selectively disrupting Bax function, but other aspects of normal reproductive performance remain defective in aged Bax-/- female mice. PMID- 9988274 TI - Interaction between Set1p and checkpoint protein Mec3p in DNA repair and telomere functions. AB - The yeast protein Set1p, inactivation of which alleviates telomeric position effect (TPE), contains a conserved SET domain present in chromosomal proteins involved in epigenetic control of transcription. Mec3p is required for efficient DNA-damage-dependent checkpoints at G1/S, intra-S and G2/M (refs 3-7). We show here that the SET domain of Set1p interacts with Mec3p. Deletion of SET1 increases the viability of mec3delta mutants after DNA damage (in a process that is mostly independent of Rad53p kinase, which has a central role in checkpoint control) but does not significantly affect cell-cycle progression. Deletion of MEC3 enhances TPE and attenuates the Set1delta-induced silencing defect. Furthermore, restoration of TPE in a Set1delta mutant by overexpression of the isolated SET domain requires Mec3p. Finally, deletion of MEC3 results in telomere elongation, whereas cells with deletions of both SET1 and MEC3 do not have elongated telomeres. Our findings indicate that interactions between SET1 and MEC3 have a role in DNA repair and telomere function. PMID- 9988275 TI - Taming of transposable elements by homology-dependent gene silencing. AB - Transposable elements can invade virgin genomes within a few generations, after which the elements are 'tamed' and retain only limited transpositional activity. Introduction of the I element, a transposon similar to mammalian LINE elements, into Drosophila melanogaster genomes devoid of such elements initially results in high-frequency transposition of the incoming transposon, high mutation rate, chromosomal nondisjunction and female sterility, a syndrome referred to as hybrid dysgenesis (for review, see refs 2-4); a related syndrome has also been described in mammals. High-frequency transposition is transient, as the number of I elements reaches a finite value and transposition ceases after approximately ten generations. It has been proposed that the I elements encode a factor that negatively regulates their own transcription, but evidence for such a mechanism is lacking. Using the hybrid dysgenesis syndrome in Drosophila as a model, we show here that transpositional activity of the I element can be repressed by prior introduction of transgenes expressing a small internal region of the I element. This autoregulation presents features characteristic of homology dependent gene silencing, a process known as cosuppression. Repression does not require any translatable sequence, its severity correlates with transgene copy number and it develops in a generation-dependent manner via germline transmission of a silencing effector in females only. These results demonstrate that transposable elements are prone to and can be tamed by homology-dependent gene silencing, a process that may have emerged during the course of evolution as a specific defense mechanism against these elements. PMID- 9988276 TI - Loci on chromosomes 2 (NIDDM1) and 15 interact to increase susceptibility to diabetes in Mexican Americans. AB - Complex disorders such as diabetes, cardiovascular disease, asthma, hypertension and psychiatric illnesses account for a large and disproportionate share of health care costs, but remain poorly characterized with respect to aetiology. The transmission of such disorders is complex, reflecting the actions and interactions of multiple genetic and environmental factors. Genetic analyses that allow for the simultaneous consideration of susceptibility from multiple regions may improve the ability to map genes for complex disorders, but such analyses are currently computationally intensive and narrowly focused. We describe here an approach to assessing the evidence for statistical interactions between unlinked regions that allows multipoint allele-sharing analysis to take the evidence for linkage at one region into account in assessing the evidence for linkage over the rest of the genome. Using this method, we show that the interaction of genes on chromosomes 2 (NIDDM1) and 15 (near CYP19) makes a contribution to susceptibility to type 2 diabetes in Mexican Americans from Starr County, Texas. PMID- 9988277 TI - Receptors for polytropic and xenotropic mouse leukaemia viruses encoded by a single gene at Rmc1. AB - The onset of leukaemia caused by type C retroviruses (MLV) in mice is accelerated by the emergence of recombinant polytropic or mink cell focus-forming (MCF) viruses. Susceptibility to infection by polytropic/MCF and also by closely related xenotropic MLV has been mapped to Rmc1 on mouse chromosome 1 (refs 5-7). To identify this gene, we introduced an expression cDNA library prepared from mouse NIH3T3 fibroblasts into nonpermissive hamster cells and screened these cells for acquired susceptibility to MCF viruses encoding beta-galactosidase and G418 resistance. From hamster cell clones identified in the screen, we recovered a mouse cDNA that maps to Rmc1 and confers MCF MLV infection when expressed in nonpermissive cell lines. It encodes a membrane protein related to Syg1p (suppressor of yeast G alpha deletion; ref. 8). The receptor-binding domain of the MCF MLV envelope protein binds specifically to Xenopus laevis oocytes that express mouse Syg1, suggesting it functions as a receptor that mediates virus entry. We also obtained the cDNA encoding human SYG1. When expressed in hamster cells, it establishes infectivity by MCF MLV as well as xenotropic MLV, which do not infect laboratory mice. PMID- 9988278 TI - Direct activation of TERT transcription by c-MYC. AB - The MYC proto-oncogene encodes a ubiquitous transcription factor (c-MYC) involved in the control of cell proliferation and differentiation. Deregulated expression of c-MYC caused by gene amplification, retroviral insertion, or chromosomal translocation is associated with tumorigenesis. The function of c-MYC and its role in tumorigenesis are poorly understood because few c-MYC targets have been identified. Here we show that c-MYC has a direct role in induction of the activity of telomerase, the ribonucleoprotein complex expressed in proliferating and transformed cells, in which it preserves chromosome integrity by maintaining telomere length. c-MYC activates telomerase by inducing expression of its catalytic subunit, telomerase reverse transcriptase (TERT). Telomerase complex activity is dependent on TERT, a specialized type of reverse transcriptase. TERT and c-MYC are expressed in normal and transformed proliferating cells, downregulated in quiescent and terminally differentiated cells, and can both induce immortalization when constitutively expressed in transfected cells. Consistent with the recently reported association between MYC overexpression and induction of telomerase activity, we find here that the TERT promoter contains numerous c-MYC-binding sites that mediate TERT transcriptional activation. c-MYC induced TERT expression is rapid and independent of cell proliferation and additional protein synthesis, consistent with direct transcriptional activation of TERT. Our results indicate that TERT is a target of c-MYC activity and identify a pathway linking cell proliferation and chromosome integrity in normal and neoplastic cells. PMID- 9988279 TI - Mice lacking link protein develop dwarfism and craniofacial abnormalities. AB - Link protein (LP), an extracellular matrix protein in cartilage, stabilizes aggregates of aggrecan and hyaluronan, giving cartilage its tensile strength and elasticity. Cartilage provides the template for endochondral ossification and is crucial for determining the length and width of the skeleton. During endochondral bone formation, hypertrophic chondrocytes die and the cartilage is replaced with bone matrix. Here, we have generated targeted mutations in mice in the gene encoding LP (Crtl1). Homozygotes showed defects in cartilage development and delayed bone formation with short limbs and craniofacial anomalies. Most Crtl1(tm1Nid/tm1Nid) mice died shortly after birth due to respiratory failure, but some survived and developed progressive dwarfism and lordosis of the cervical spine. They showed small epiphysis, slightly flared metaphysis of long bones and flattened vertebrae, characteristic of spondyloepiphyseal dysplasias. The cartilage contained significantly reduced aggrecan depositions in the hypertrophic zone, and decreased numbers of prehypertrophic and hypertrophic chondrocytes. Reduced Indian hedgehog (Ihh) expression was observed in prehypertrophic chondrocytes, and apoptosis was inhibited in hypertrophic chondrocytes. These results indicate that LP is important for the formation of proteoglycan aggregates and normal organization of hypertrophic chondrocytes, and suggest that cartilage matrix has a role in chondrocyte differentiation and maturation. PMID- 9988281 TI - Localization of human BRCA1 and its loss in high-grade, non-inherited breast carcinomas. AB - Although the link between the BRCA1 tumour-suppressor gene and hereditary breast and ovarian cancer is established, the role, if any, of BRCA1 in non-familial cancers is unclear. BRCA1 mutations are rare in sporadic cancers, but loss of BRCA1 resulting from reduced expression or incorrect subcellular localization is postulated to be important in non-familial breast and ovarian cancers. Epigenetic loss, however, has not received general acceptance due to controversy regarding the subcellular localization of BRCA1 proteins, reports of which have ranged from exclusively nuclear, to conditionally nuclear, to the ER/golgi, to cytoplasmic invaginations into the nucleus. In an attempt to resolve this issue, we have comprehensively characterized 19 anti-BRCA1 antibodies. These reagents detect a 220-kD protein localized in discrete nuclear foci in all epithelial cell lines, including those derived from breast malignancies. Immunohistochemical staining of human breast specimens also revealed BRCA1 nuclear foci in benign breast, invasive lobular cancers and low-grade ductal carcinomas. Conversely, BRCA1 expression was reduced or undetectable in the majority of high-grade, ductal carcinomas, suggesting that absence of BRCA1 may contribute to the pathogenesis of a significant percentage of sporadic breast cancers. PMID- 9988280 TI - Increased insulin sensitivity and hypoglycaemia in mice lacking the p85 alpha subunit of phosphoinositide 3-kinase. AB - The hallmark of type 2 diabetes, the most common metabolic disorder, is a defect in insulin-stimulated glucose transport in peripheral tissues. Although a role for phosphoinositide-3-kinase (PI3K) activity in insulin-stimulated glucose transport and glucose transporter isoform 4 (Glut4) translocation has been suggested in vitro, its role in vivo and the molecular link between activation of PI3K and translocation has not yet been elucidated. To determine the role of PI3K in glucose homeostasis, we generated mice with a targeted disruption of the gene encoding the p85alpha regulatory subunit of PI3K (Pik3r1; refs 3-5). Pik3r1-/- mice showed increased insulin sensitivity and hypoglycaemia due to increased glucose transport in skeletal muscle and adipocytes. Insulin-stimulated PI3K activity associated with insulin receptor substrates (IRSs) was mediated via full length p85 alpha in wild-type mice, but via the p50 alpha alternative splicing isoform of the same gene in Pik3r1-/- mice. This isoform switch was associated with an increase in insulin-induced generation of phosphatidylinositol(3,4,5)triphosphate (PtdIns(3,4,5)P3) in Pik3r1-/- adipocytes and facilitation of Glut4 translocation from the low-density microsome (LDM) fraction to the plasma membrane (PM). This mechanism seems to be responsible for the phenotype of Pik3r1-/- mice, namely increased glucose transport and hypoglycaemia. Our work provides the first direct evidence that PI3K and its regulatory subunit have a role in glucose homeostasis in vivo. PMID- 9988282 TI - Primary care of long-stay nursing home residents: approaches of three health maintenance organizations. AB - OBJECTIVE: To describe the innovative programs of three health maintenance organizations (HMOs) for providing primary care for long-stay nursing home (NH) residents and to compare this care with that of fee-for-service (FFS) residents at the same NHs. DESIGN: Cross-sectional interviews and case-studies, including retrospective chart reviews for 1 year. SETTING: The programs were based in 20 community-based nursing homes in three regions (East, West, Far West). PARTICIPANTS: Administrative and professional staff of HMOs in three regions and 20 NHs; 215 HMO and 187 FFS residents at these homes were studied. MAIN OUTCOME MEASURES: Emergency department (ED) and hospital utilization. RESULTS: All HMO programs utilized nurse practitioner/physician's assistants (NP/PA), but the structural configuration of physicians' (MD) practices differed substantially. At nursing homes within each region, all three HMO programs provided more total (MD plus NP/PA) visits per month than did FFS care (2.0 vs 1.1, 1.3 vs .6, and 1.4 vs .8 visits per month; all P < .05). The HMO that provided the most total visits had a significantly lower percentage of residents transferred to EDs (6% vs 16%, P = .048), fewer ED visits per resident (0.1 vs .4 per year, P = .027), and fewer hospitalizations per resident (0.1 vs .5 per year, P = .038) than FFS residents; these differences remained significant in multivariate analyses. However, the other two programs did not achieve the same benefits on healthcare utilization. CONCLUSIONS: HMO programs for NH residents provide more primary care and have the potential to reduce ED and hospital use compared with FFS care. However, not all programs have been associated with decreased ED and hospital utilization, perhaps because of differences in structure or implementation problems. PMID- 9988283 TI - Use of primary care teams by HMOS for care of long-stay nursing home residents. AB - OBJECTIVE: To characterize the use of formal primary care programs by health maintenance organizations (HMOs) for their members who are long-stay residents of nursing homes. DESIGN: Using mail survey techniques, 34 Medicare risk-contracting HMOs with the largest Medicare beneficiary enrollments were asked to complete a written questionnaire. HMOs were asked how they evaluate care in nursing home settings and whether they operate a formal primary care program for members who are long-stay nursing home residents. Those reporting they had programs were asked about the program features, participation in the program, roles performed by clinical practitioners, and clinical caseloads. Surveys were completed by 21 (61.8%) of the HMOs. PARTICIPANTS: HMO management personnel who know the primary care programs the HMOs operate in affiliated nursing homes. MEASUREMENTS: Descriptive summaries of the HMOs' responses to the survey questions were generated. For HMOs with primary care programs, caseloads of physicians and nurse practitioners were estimated using survey data reported by the HMOs. RESULTS: Eight (38.1%) of the responding HMOs operate formal primary care programs in affiliated nursing homes. HMOs with programs consider more factors than non program HMOs in evaluating care for nursing home residents. Reasons cited most frequently for not having a program are costs and too few nursing home residents. The most common primary care program features are designated physicians and use of physician extenders. CONCLUSIONS: Survey findings point to the potential importance of formal HMO primary care programs for long-term nursing home residents, which may expand with growth in the older population and Medicare managed care. Program adoption, however, may depend on sufficient resident participation to be financially feasible. PMID- 9988284 TI - Age-related differences in management of heart disease: a study of cardiac medication use in an older cohort. Pacemaker Selection in the Elderly (PASE) Investigators. AB - BACKGROUND: Previous studies have suggested suboptimal use of cardiac medications for secondary prevention after myocardial infarction (MI) and atrial fibrillation (AF), especially among older people. OBJECTIVE: To determine whether patients older than 75 years are less likely than those aged 65 to 74 to be prescribed medications with evidence-based indications, including angiotensin-converting enzyme (ACE) inhibitors for left ventricular dysfunction (LVD) and/or diabetes mellitus (DM), aspirin and/or beta-blockers for those with a history of MI, and warfarin for chronic AF. DESIGN: A retrospective cohort study. SETTING: Twenty nine hospitals, predominantly tertiary-care institutions. PARTICIPANTS: A total of 407 patients randomized to ventricular or dual-chamber pacing from February 26, 1993, to September 30, 1994, in the Pacemaker Selection in the Elderly (PASE) trial. MEASUREMENTS: A review of the patient's medical history and a physical exam at study enrollment, three follow-up timepoints, and a study closeout. RESULTS: Patients older than 75 years with LVD and/or DM were less likely to be prescribed ACE inhibitors (OR = .56 (0.31-1.00)); patients older than 75 with a history of MI were less likely to be taking aspirin (OR = .43 (0.19-.95)), and patients older than 75 with AF were less likely to be prescribed warfarin (OR = .18 (0.05-.61)). Patients older than 75 years of age with any or all of the conditions studied were less likely to be prescribed indicated medications than those ages 65 to 74 (OR = .35 (0.18-.70)), after controlling for between-group differences in comorbidity, gender, and number of noncardiac medications. CONCLUSION: Older age is a significant independent negative correlate of evidence based cardiac medication use in this cohort. Causes for this finding need to be explored. PMID- 9988285 TI - Gender differences in the sequelae of hospitalization for acute myocardial infarction among older adults. AB - OBJECTIVE: To examine the effect of gender differences among older adults hospitalized for an acute myocardial infarction (AMI) on subsequent health outcomes. DESIGN: Secondary analysis of the Longitudinal Study on Aging. Data from baseline interviews (1984) and three biennial (1986, 1988, and 1990) re interviews were linked to Medicare hospitalization and National Death Index records for 1984-1991. PARTICIPANTS: A total of 6071 community-dwelling adults aged 70 years or older at baseline. METHODS: Pooled and stratified multivariable models were used to examine gender differences in the independent effects of being hospitalized for an AMI on all-cause mortality, the risk and volume of subsequent hospitalization, and increases in the number of functional limitations. Two comparison groups were used. RESULTS: Three hundred fifty-seven AMI cases (6%; 172 women and 185 men) were compared with 3976 hospitalized controls and 1738 nonhospitalized controls. The risk of all-cause mortality for AMI cases was greater than that for either hospitalized controls or nonhospitalized controls (referent), and this increased risk was significantly (P < .001) stronger for women (adjusted hazards ratio (AHR) = 14.24, 95%CI = 10.99, 18.46) than for men (AHR = 9.91, 95%CI = 7.75, 12.67). Overall, AMI cases were also more likely to be hospitalized subsequently than the hospitalized controls (referent; adjusted odds ratio (AOR) = 1.47, 95%CI = 1.17, 1.85), although in the stratified analysis this association held for men (AOR = 1.73, 95%CI = 1.25, 2.41) but not for women (AOR = 1.25, 95%CI = .90, 1.73). Among those subsequently hospitalized, both women and men AMI cases consumed more hospital resources than the hospitalized controls, and there were gender differences suggesting that the effects on total charges and length of stay were greater for women than for men with AMI. Finally, although the AMI cases had greater adjusted mean increases in the number of instrumental activities of daily living limitations and lower body limitations than the nonhospitalized controls, they were no worse off than the hospitalized controls, and there were no gender differences in those effects. CONCLUSION: Relative to the appropriate comparison groups, hospitalization for an AMI increases the risk of death and the total costs and lengths of stay of subsequent hospitalizations for women more than for men. Therefore, increased primary prevention, diagnosis, and treatment efforts should be directed toward women. PMID- 9988286 TI - Gender differences in cognitive function with age: the Rancho Bernardo study. AB - BACKGROUND: Estrogen deficiency has been proposed as a cause of memory loss in postmenopausal women. If true, men should have less memory loss with age than women. The present study is designed to examine the postulated effect of estrogen on memory by studying the effect of gender on the age-related decline in cognitive function. METHODS: Cross-sectional study of 800 women and 551 men aged 65 to 95 years, members of the community-based Rancho Bernardo Study (begun in 1972 and 1974) who completed the Beck Depression Inventory in 1984-1987 and 12 standardized tests of cognitive function in 1988-1991. All participants were white, middle to upper-middle class, relatively well educated, and ambulatory. At all visits, use of estrogen therapy was ascertained and validated. RESULTS: Test performance worsened with age in both sexes, with similar patterns in men compared with women who were current, past, or never users of estrogen. Between gender comparisons of the slope for age on each cognitive function test after adjustment for education, depressed mood, and estrogen use (in women) indicated that men had a significantly steeper decrement with age than women on the Buschke total recall and long-term memory tests (P <. 001), on the immediate and delayed recall tasks of the visual reproduction tests (P < .01 and .05, respectively), and on category fluency (P < .05). Similar results were obtained when gender comparisons included only women who had never used estrogen. CONCLUSION: These weak or absent gender differences in decline in cognitive function with age do not support the thesis that estrogen deficiency is associated with a decline in cognitive function in postmenopausal women. PMID- 9988287 TI - Effectiveness of inactivated influenza vaccine among nursing home residents during an influenza type A (H3N2) epidemic. AB - OBJECTIVES: To evaluate the use of influenza vaccine in nursing homes and its effectiveness in reducing the likelihood of influenza-like illness. DESIGN: A retrospective case-control study with active identification of influenza infection. SETTING: All nursing homes in a seven-county study area in southern lower Michigan were eligible for participation. Analyses were based on data collected from 23 homes with documented influenza transmission. PARTICIPANTS: Persons aged 65 years or older who were residents of the nursing homes under study during the influenza type A(H3N2) outbreak in 1989-1990. MEASUREMENTS: Residents were identified as cases or controls based on occurrence of febrile respiratory illness meeting a case definition. Demographic and underlying illness information were gathered as were data on the use of influenza vaccine, antibiotics, and antivirals. Characteristics of the nursing homes were also recorded. Logistic regression analyses were carried out to determine vaccine effectiveness. MAIN RESULTS: Determinants of vaccine use were different from those observed in a parallel community-based study. In a multivariate model that considered the effects of resident and nursing home characteristics, vaccinated residents were significantly less likely than those who were not vaccinated to have an influenza-like illness (OR = .58 (95% CI, .43-.78), P < .001, imputed vaccine effectiveness estimate of 42%). Vaccination was more effective in younger residents (those aged 65 to 84) then in older residents (those older than 84 years). CONCLUSIONS: Influenza vaccination was effective in reducing the likelihood of influenza-like illness in nursing home residents. Effectiveness appeared to be related to age, which may function as a surrogate for related immunologic factors. Older nursing home residents should be targeted for newer vaccines and/or potential prophylactic use of antivirals. PMID- 9988288 TI - Medication adherence in rheumatoid arthritis patients: older is wiser. AB - OBJECTIVES: To create a profile of individuals nonadherent to their medications in an age-stratified sample (ages 34-84) of community-dwelling rheumatoid arthritis patients. The relative contributions of age, cognitive function, disability, emotional state, lifestyle, and beliefs about illness to nonadherence were assessed. DESIGN: A direct observation approach was used in conjunction with structural equation modeling. All participants were administered a preliminary assessment battery. Medications were then transferred to vials with microelectronic caps that recorded medication events for all medications for the next 4 weeks. PARTICIPANTS AND SETTING: A volunteer sample of 121 community dwelling rheumatoid arthritis (RA) patients were recruited from newspaper ads, posters, and via informal physician contact from private rheumatology practices in Atlanta and Athens, Georgia. Written verification of the RA diagnosis and a disease severity rating were obtained from personal physicians before patients were enrolled in the study. Patients were tested in a private physician's office, and their medication adherence was monitored electronically for a month in their every-day work and home settings. MEASUREMENTS AND RESULTS: Structural equation modeling techniques were used to develop a model of adherence behavior. Cognitive and psychosocial measures were used to construct latent variables to predict adherence errors. The model of medication adherence explained 39% of the variance in adherence errors. The model demonstrated that older adults made the fewest adherence errors, and middle-aged adults made the most. A busy lifestyle, age, and cognitive deficits predicted nonadherence, whereas coping with arthritis related moods predicted adherence. Illness severity, medication load, and physical function did not predict adherence errors. Omission of medication accounted for nearly all errors. CONCLUSION: Despite strong evidence for normal, age-related cognitive decline in this sample, older adults had sufficient cognitive function to manage medications. A busy lifestyle and middle age were more determinant of who was at risk of nonadherence than beliefs about medication or illness. Thus, practicing physicians should not assume that older adults have insufficient cognitive resources to manage medications and that they will be the most likely to make adherence errors. Very busy middle-aged adults seem to be at the greatest risk of managing medications improperly. PMID- 9988289 TI - Risk of a new benzodiazepine prescription in relation to recent hospitalization. AB - OBJECTIVE: To determine if recent hospital admission was associated with new outpatient prescribing of benzodiazepines among community-dwelling older people. DESIGN: Nested case-control study using administrative data sets of the provincial health insurance board. SETTING: Province of Quebec. PARTICIPANTS: Cases were 4127 community-dwelling older people who were newly dispensed a benzodiazepine during an 8-month period in 1990. Controls were 16,486 community dwelling older people who were dispensed any drug (except a benzodiazepine) on the same day as the case-defining index prescription. EXPOSURE AND OUTCOME MEASURES: Admission to an acute care hospital within a 30-day period before a new dispensing of a benzodiazepine. Other variables measured were patient age, gender, number of ambulatory physician visits, healthcare region, Chronic Disease Score (CDS), and use of drugs for depression and psychosis. RESULTS: Cases were more than three times as likely as controls to have been hospitalized in the 30 day period before the index date (adjusted odds ratio (OR) 3.09; 95% CI, 2.78 3.45). The use of prescription drugs for physical health problems modified this association in that cases who used more medication were also more likely to receive a new benzodiazepine prescription following a recent hospital admission (adjusted OR 4.09; 95% CI, 3.59-4.65 when the CDS was equal to 5 vs adjusted OR 1.96; 95% CI, 1.66-2.31 when the CDS was equal to 0). CONCLUSIONS: Recent hospitalization confers an increased risk of a new outpatient benzodiazepine prescription among community-dwelling older people in Quebec. Those who use more medication, and who may be more vulnerable to drug-related adverse events, are more likely to be newly dispensed a benzodiazepine following a recent, acute-care hospital admission. PMID- 9988290 TI - Prevalence and risks of dementia in the Japanese population: RERF's adult health study Hiroshima subjects. Radiation Effects Research Foundation. AB - OBJECTIVES: To study the prevalence rate of dementia and its subtypes in Japan and to investigate the relationship of risk factors, such as demographic features and disease history, to the prevalence of Alzheimer's disease or vascular dementia. DESIGN: A prevalence study within a longitudinal cohort study. SETTING: The original Adult Health Study (AHS) cohort consisted of atomic-bomb survivors and their controls selected from residents in Hiroshima and Nagasaki using the 1950 national census supplementary schedules and the Atomic Bomb Survivors Survey. Since 1958, the AHS subjects have been followed through biennial medical examinations. PARTICIPANTS: Subjects were 637 men and 1585 women aged 60 years or older in the AHS cohort. Forty-eight subjects resided in hospitals and institutions. MEASUREMENTS: In addition to the biennial medical examinations ongoing since 1958, a screening test for cognitive impairment (CASI) was conducted by trained nurses between September 1992 and September 1996. The prevalence of dementia and its subtypes was assessed in 343 subjects suspected to have dementia and in 272 subjects with high CASI scores who were selected randomly. RESULTS: The prevalence of dementia based on DSM III/R criteria, using neurological examination, the IQCODE, and CDR > or = 1, was 7.2%. The prevalence of Alzheimer's disease was 2.0% in men and 3.8% in women, and the prevalence of vascular dementia was 2.0% in men and 1.8% in women. The relationship of risk factors to Alzheimer's disease or vascular dementia was investigated by the multivariate logistic linear regression analysis. Odds ratios of Alzheimer's disease for age (in 10-year increments), attained education (in 3-year increments), history of head trauma, and history of cancer are 6.3, 0.6, 7.4, and 0.3, respectively. Odds ratios of vascular dementia for age, history of stroke, and history of hypertension are 2.0, 35.7, and 4.0, respectively. Neither type of dementia showed any significant effect of sex or radiation exposure. CONCLUSION: This study is the first study of Japanese dementia rates carried out with a protocol similar enough to that of a US study to allow meaningful comparisons. The prevalence rates demonstrated are more similar to US rates than were found in many previous reports in Japan. PMID- 9988291 TI - Contrasting results between caregiver's report and direct assessment of activities of daily living in patients affected by mild and very mild dementia: the contribution of the caregiver's personal characteristics. AB - OBJECTIVE: To determine the level of agreement between the primary caregiver's report on patient activities of daily living (ADLs) and ADLs assessed directly in a sample of patients affected by very mild and mild dementia and to assess whether this agreement is influenced by the caregiver's depressive symptoms and burden. PATIENTS AND METHODS: Data were obtained from the baseline sample of the Mild Dementia Longitudinal Study, consisting of 111 consecutive patients affected by dementia with very mild to mild functional impairment (grades .5 and 1 on the Clinical Dementia Rating Scale). As is usual for patients referred to our Alzheimer's Unit, anamnestic, cognitive, functional and behavioral information are collected from the primary caregiver. Along with sociodemographic characteristics, caregivers' depressive symptoms (Beck Depression Inventory Scale) and burden (Nowak and Guest's Caregiver Burden Inventory Scale) were also evaluated. Patients underwent a performance-based assessment of the activities of daily living (DAFS) and direct assessment of physical function with the Physical Performance Test (PPT). Caregiver's report and direct observation have been compared for the following ADLs: dressing, toileting, walking, telephone use, shopping, and money use. Discriminant analyses were conducted to examine the degree of agreement between caregiver-report functional status and performance based measures and whether additional agreement is attributable to caregiver's burden and depressive symptoms. RESULTS: The strength of the association between the caregiver's report and performance-based measures of ADLs is high for motor performance (walking), moderate to good for dressing, but only moderate for telephone, money use, and shopping. No association was found for toileting. The discrepancies between caregiver report and performance-based assessment were influenced substantially by the burden caused by demands and restrictions on a caregiver's time. CONCLUSIONS: With the exception of motor performance (walking), the caregiver's report and the performance-based assessment of functional status measure different aspects of a patient's functional status. Contrasts between the caregiver's report and observed ADL performance in mildly and very mildly demented patients are influenced by the caregiver's burden. PMID- 9988292 TI - An evaluation of a family visit education program. AB - OBJECTIVES: This study was designed to examine the impact of the Family Visit Education Program (FVEP) on family members, nursing staff, and nursing home residents with dementia. DESIGN: The study employed a 2 x 3 single-blind, randomized control group design with two study conditions, FVEP or usual care (UC), and three times of measurement, baseline, 3-months, and 6-months. SETTING: The study was conducted in five skilled-care nursing homes that ranged in size from 120 to 300 beds. PARTICIPANTS: Sixty-six residents with dementia and their primary visitor were randomly assigned to FVEP (n = 32) or UC (n = 34). MEASUREMENTS: Residents were assessed for (1) psychosocial functioning, (2) depression, (3) agitated behavior, and (4) degree of positive social interaction. Nursing staff were assessed for changes in the time and methods used to manage problem behaviors. Visitors were assessed for (1) dementia management skills, (2) extent of perceived caregiving hassles, and (3) visit satisfaction. RESULTS: FVEP was effective for reducing residents' problem behaviors and for decreasing their symptoms of depression and irritability. It was also effective for improving the way family members and other visitors communicated with residents, but, with the exception of reducing the use of mechanical restraints, it was not effective in changing nurses' management of residents' behavior problems. CONCLUSIONS: It is possible to educate family members to communicate and interact more effectively with nursing home residents with dementia. This has beneficial effects on residents but not on nursing staff's management of problem behaviors. PMID- 9988293 TI - Misclassification and selection bias when identifying Alzheimer's disease solely from Medicare claims records. AB - BACKGROUND: Medicare claims as the basis for health condition adjustments is becoming a method of choice in capitation reimbursement. A recent study has found that claims-based beneficiary classification for Alzheimer's disease produces lower prevalence estimates and higher average costs than previous healthcare cost studies in this population. These sets of studies differ in data sources, period length, and in their specification of dementia. OBJECTIVES: Participants in the Medicare Alzheimer's Disease Demonstration (MADDE) provide a sample of persons known to have some form of dementia. This group is used to test the adequacy of claims data for identifying eligible cases and any bias in expenditure differences between those flagged or not flagged by a claim in a given period. DESIGN: A prospective cohort design using up to 36 months of claims data. SETTING: The demonstration enrolled 4166 participants in treatment, and 3942 in a control group in eight communities across the US. Cases were combined in this analysis. PARTICIPANTS: Persons with available Medicare Part A & B claims data: those receiving care under fee for service reimbursement were used in the analysis. A total of 5379 MADDE cases received fee for service care during 1991 and 1992, the period of primary interest in the analysis. MEASUREMENT: Client health and functional status interviews and Medicare Part A & B claims. RESULTS: Less than 20% of MADDE participants were classified with Dementia of the Alzheimer type (DAT) from a single year of claims although 68% had a DAT diagnosis from a referring physician. Annualized expenditures were 1.7 times higher among those with DAT from claims compared with those known otherwise to have dementia but who had not been identified with this condition from Medicare claims. CONCLUSION: Underclassification of dementia from claims records can be partially remedied by increasing the period during which claims are compiled, but additional diagnostic sources will likely be needed to increase prevalence counts closer to 100% of true cases. Risk adjustment based on a single year of reported claims expenditures may overpay providers, at least in the short term, because payment incentives will likely increase prevalence reporting. PMID- 9988294 TI - Low serum calcidiol concentration in older adults with reduced muscular function. AB - OBJECTIVE: To examine the association between muscular function and the serum concentrations of 25-hydroxyvitamin D (calcidiol) and 1,25-dihydroxyvitamin D (calcitriol). DESIGN: A randomized population survey. Baseline measurements of serum calcidiol and calcitriol concentrations and assessment of muscular function (hand grip strength, ability to climb stairs, outdoor activity, and fall occurrence). SETTING: The Medical department, Aker University Hospital, Oslo, and subjects' homes. PARTICIPANTS: Two hundred forty-six recently hospitalized older patients and 103 randomly selected older people living at home. MEASUREMENTS: Serum concentration of calcidiol and calcitriol in relation to muscle function. MAIN RESULTS: Reduced muscle function was associated with low calcidiol levels. In both the hospital group and the home group, calcidiol concentrations correlated positively to arm muscle strength (r = .22, P < .001; r = .37, P < .001), ability to climb stairs (r = -.16, P < .05; r = -.42, P = < .001), physical activity (r = -.27, P < .001; r = -.31, P < .001), and the absence of fall occurrences (r = -.27, P < .001; r = -.31, P = .004). Calcitriol showed an association with physical activity in the hospital group (r = -.19, P < .05), and with fall last month in the home group (r = -.22, P < .05). CONCLUSIONS: Older people with reduced muscle function often had reduced levels of calcidiol serum concentration. Low levels of calcidiol were not associated with signs of general undernutrition, such as low body mass, or with reduced arm-muscle circumference or triceps skinfold thickness. This finding may suggest a physiological role for calcidiol in muscle function. Reduced muscle strength increased disability in our older subjects, which may be improved by vitamin D supplementation in vitamin D deficient subjects. PMID- 9988295 TI - A patient-centered approach to advance medical planning in the nursing home. AB - OBJECTIVE: The objective of this study is to determine whether nursing home residents or their surrogates are willing and able to prioritize their goals for care and to demonstrate how these rankings can form the basis of a specific pattern of medical care. DESIGN: A prospective, descriptive study. SETTING: A 40 bed nursing unit for residents with mild to moderate impairments in a 725-bed teaching nursing home. RESULTS: Overall, 78% of patients or their families were willing to prioritize their goals, allowing the investigators to infer a pattern of care. The goals were interpreted as implying an intensive pattern in 21%, a comprehensive pattern in 16%, a basic pattern in 18%, palliation in 18%, and comfort only in 6% of residents. Goals chosen by residents who were able to select for themselves translated into more aggressive care than did the goals selected by surrogates. CONCLUSION: Goal-centered advance medical planning can be initiated in nursing homes by asking residents or their surrogates to prioritize their goals of care. These prioritizations can form the foundation for specific patterns of care. PMID- 9988296 TI - Pharmacologic treatment of hypersexuality and paraphilias in nursing home residents. AB - PURPOSE: To discuss the pharmacologic options for treatment of hypersexuality or paraphilias in nursing home residents. DATA SOURCES: A MEDLINE search was conducted for English-language articles published over the past 20 years and was supplemented by a search of bibliographies of relevant articles. STUDY SELECTION: Case reports of pharmacologic treatment of hypersexual or paraphilic behavior were selected only if the patient receiving treatment was an older person and/or cognitively impaired. DATA EXTRACTION: Case reports were grouped according to the class of the pharmacologic agent used (antiandrogens, estrogens, GnRH analogues, or serotonergic drugs). Each case report was evaluated for pharmacologic agent administered, route of administration, duration of therapy, therapeutic response, and incidence of side effects. CONCLUSIONS: Nursing home residents who display hypersexual or paraphilic behavior are extremely difficult to manage. Before initiating pharmacotherapy to control unwanted sexual behaviors, the current drug regimen should be evaluated carefully for drugs that may be causing or exacerbating the behavior. Case reports suggest that antiandrogens, estrogens, GnRH analogues, and serotonergic medications may be useful when other methods have failed. Controlled comparative trials of these agents are needed to establish their efficacy clearly. PMID- 9988297 TI - Aging and postural control: postural perturbations caused by changing the visual anchor. AB - OBJECTIVE: To determine the effect of modifying the stable visual anchor on the postural stability of older individuals. The visual anchor was changed by opening doors similar to those found in an elevator cage. Lighting intensities inside and outside the cage were varied to create increasing or decreasing luminosity conditions. The effect of adding a cognitive load (counting backwards) was also tested. DESIGN: A controlled laboratory study. SETTING: Tests performed in a balance laboratory. MEASUREMENTS: Sensory and clinical measurements to insure the integrity of the central and peripheral nervous system. Measures of balance were derived from the recordings of the center of foot pressure. These measures included range and speed of the center of foot pressure. PARTICIPANTS: Eight older, community-dwelling subjects and nine young subjects participated. A sensorimotor evaluation was used to insure that all older individuals were free from any pathologies affecting postural stability. All participants had a low score (indicating high balance confidence) on the Falls Efficacy Scale and no history of falls. RESULTS: Older individuals were affected by modification of the stable visual anchor induced by the opening of doors similar to that of an elevator cage. They showed greater ranges of the center of foot pressure (COP) and speed of the COP after than before the opening of the doors. Furthermore, the increased ranges and speed were two to three times greater than that observed for the young subjects. A lighting intensity considered as comfortable for reading inside the elevator affected the overall postural stability of the older participants negatively. Counting backwards also decreased their overall stability. CONCLUSION: Changing the stable visual anchor, as when exiting an elevator cage, could be a significant risk factor for older persons. Moreover, when combined with a cognitive load or lower lighting intensity inside the elevator cage, the negative effects on the postural stability of older persons are exacerbated. PMID- 9988298 TI - Managed care for older people: a primer for the geriatrician. AB - Managed care for older people is growing at a very rapid rate. Many geriatricians and primary care providers are interested in this area but have limited sources of information to guide their decision-making about whether to participate in these programs. This review provides a basic overview of managed care for older people, including plan types and roles that geriatricians may choose in participating in these programs. Risk and value are central concepts that impact managed care of this population. Several changes in Medicare Managed Care have occurred with the passage by Congress of the Balanced Budget Act of 1997. Geriatricians are strongly encouraged to participate in managed care as it offers the potential for improved models of care delivery for older adults. PMID- 9988299 TI - Long-term care in its infancy. PMID- 9988300 TI - Underutilization of cardiac medications in the Pacemaker Selection in the Elderly study. PMID- 9988301 TI - Assessment of caregiver's competence in dealing with the burden of caregiving for a dementia patient: a Short Sense of Competence Questionnaire (SSCQ) suitable for clinical practice. PMID- 9988303 TI - Ileus, a clinical sign of congestive heart failure in older people. PMID- 9988302 TI - Age effects on pupil dilation among Alzheimer's patients. PMID- 9988304 TI - Depression of T helper-1 and tuberculin responses in older bed-bound patients. PMID- 9988305 TI - Dynamics of functional recovery from stroke in specialist settings. PMID- 9988306 TI - Chronic diarrhea and increasing disability in an older woman due to an unusual cause. PMID- 9988307 TI - Interleukin-12 and the host response to parasitic helminths; the paradoxical effect on protective immunity and immunopathology. AB - In general, helminth infections are associated with the development of dominant Th2-mediated immune responses which may be host protective but can also be the cause of immunopathology. Interleukin 12 (IL-12) is known to be a potent inhibitor of Th2 immune responses and as such it might be expected to have an important modulatory role in helminth-induced immune responses. In this review, we discuss the effect of IL-12 on susceptibility to infection, protective immunity and immunopathology, in the context of exposure to a range of helminths including intestinal nematodes, filariae and schistosomes. It is apparent that the effects of IL-12 are complex and can be beneficial as well as detrimental for the host. The precise role of IL-12 depends upon a number of factors including the type of helminth and the specific tissue involved in the inflammatory response. PMID- 9988309 TI - T-cell activity associated with secondary infections and implanted cysts of Echinococcus granulosus in BALB/c mice. AB - Selected cytokine profiles of lymphocytes were assessed in BALB/c mice infected with protoscoleces of Echinococcus granulosus. Late stages of the infection (three months+) were characterized by more dominant Th2 activity with elevated IL 4 and IL-10 and reduced IFN-gamma output by Con-A and antigen stimulated splenocytes. Circumparasitic leucocytes produced mainly IL-10 by five months post infection. A peak in IFN-gamma production in the first month of infection may suggest Th1 or Th0 activity at this time and this may be correlated with initial protoscolex death. In addition, cytokine profiles from mice implanted with intact hydatid cysts were also assessed. At two weeks post implantation all cysts were still viable and cytokine production was characterized mainly by elevated IL-10 production. However, at four months post implantation, some of the cysts from two mice had been killed whilst all cysts in the remaining mouse remained viable. In the mice where dead cysts were present, elevated levels of IFN-gamma were detected from splenocytes and circumparasitic cells. Elevated IL-4 was also evident with the splenocytes. In the mouse with viable cysts IFN-gamma production was reduced Results indicate that IFN-gamma(Th1) activity may be correlated with killing of both protoscoleces and established cysts of E. granulosus. PMID- 9988308 TI - Cellular immune responses in cattle experimentally infected with Neospora caninum. AB - Neospora caninum has recently been identified as an important cause of infectious abortion in cattle. The parasite is closely related to Toxoplasma gondii, but the two species are antigenically distinct. To examine cell proliferative responses and the induction of IFN-gamma in experimentally infected cattle, four 2-4 months old calves were subcutaneously inoculated with N. caninum tachyzoites. Peripheral blood mononuclear cells were collected regularly and stimulated in vitro with a crude lysate of N. caninum or T. gondii tachyzoites. Significant proliferative responses to N. caninum antigen were recorded in all calves from days 4-6 postinoculation. This response was accompanied by production of high levels of IFN-gamma. Although the calves remained seronegative to T. gondii, while seroconverting to N. caninum, stimulation with T. gondii lysate resulted in cell proliferation of a similar magnitude as that obtained using the N. caninum lysate. However, the T. gondii lysate appeared less effective than the N. caninum lysate to stimulate IFN-gamma production. Cells taken from uninfected control animals did not show any significant proliferation to either N. caninum or T. gondii antigen and no IFN-gamma was produced. These results suggest that the two parasites may possess cross-reacting T-cell epitopes, but that the T cells specific for N. caninum may have a different functional capacity. This highlights the need to investigate the antigen specificity and cytokine profile of T cells from infected animals to help understand their role in immunity to N. caninum. PMID- 9988311 TI - Relevance of circulating antigen detection to follow-up experimental and human cystic hydatid infections. AB - We analysed specific antibody (Ab) and circulating antigen (CAg) profiles along experimental mouse infection using as control a group of mice immunized with intact but dead parasites. Results from this experiment showed an early major CAg peak followed by a larger Ab peak which partially overlaps with other minor CAg peaks. These results suggest that CAg may be a marker of early mouse infection. In order to study the relevance of these findings in humans we similarly analysed by ELISA 148 sera provided by retrospective post-surgical follow-up of 19 patients. Available records showed that 14 patients developed new cysts one to ten years after surgery while no new disease was observed in the-other five. Some of the former patients showed CAg, as early as two months after surgery while no CAg was observed in the other five patients at any time. In addition, a collection of 38 sera obtained before surgery were similarly tested and five of them showed only CAg, while 18 showed only Ab and 12 sera showed Ab&CAg. These results in humans are consistent with the findings in the mouse experimental model and suggest that CAg may be an early marker of hydatid infection, thus being relevant for post-surgical follow-up. PMID- 9988310 TI - Epitope specificities and antibody responses to the EG95 hydatid vaccine. AB - Antibody isotype and epitope specificities were examined in sheep immunized with EG95, a protective recombinant vaccine against hydatid disease. All sheep immunized with EG95 as a fusion protein with glutathione S-transferase (GST) produced prominent IgG antibodies against the EG95 portion of the protein. Linear, antibody-binding epitope specificities of EG95 were mapped using a series of 25 overlapping synthetic peptides. Three immunodominant regions were identified which generated specific IgG1 and IgG2 antibodies in the majority of vaccinated sheep. These regions corresponded to the EG95-derived sequences SLKAVNPSDPLVYKRQTAKF, DIETPRAGKKESTVMTSGSA and SALTSAIAGFVFSC. An additional immunogenic region was identified which induced almost exclusively IgG2 antibody. This epitope was located within the sequence TETPLRKHFNLTPV. The anti-parasitic, protective effects of the EG95 vaccine correlated with the detection of specific antibody to two or more of the four linear immunogenic regions. The identification of these immunogenic peptides of EG95 maybe useful in the development of a synthetic peptide vaccine as a derivative of the EG95 recombinant. PMID- 9988312 TI - Induction of signalling anergy via the T-cell receptor in cultured Jurkat T cells by pre-exposure to a filarial nematode secreted product. AB - Filarial nematodes constitute major causes of morbidity in the Tropics. The worms have a life-span exceeding five years, a longevity which is considered to reflect at least in part, their ability to interfere with host lymphocyte responsiveness. To date the molecular mechanisms underlying this ability have not been defined but we now demonstrate that ES-62, a phosphorylcholine (PC)-containing glycoprotein released by the rodent filarial parasite Acanthocheilonema viteae, is able to render Jurkat T cells anergic to intracellular signalling via the antigen receptor (TCR). In particular, ES-62 acts by modulating activation of the tyrosine kinases Fyn, Lck and ZAP-70 leading to selective disruption of TCR coupling to the phospholipase D, protein kinase C, phosphoinositide-3-kinase and RasMAPkinase signalling cascades. These cascades are key elements in the transduction of transcriptional and proliferative signals following ligation of TCR. As PC-containing secreted products (PC-ES) are also released by human filarial parasites, our data suggest that PC-ES may play a role in the induction of T lymphocyte hyporesponsiveness observed during filarial infections. PMID- 9988314 TI - Predicting mosquito repellent potency of N,N-diethyl-m-toluamide (DEET) analogs from molecular electronic properties. AB - Specific molecular electronic properties of 30 N,N-diethyl-m-toluamide (DEET) analogs demonstrate functional dependence with their reported duration of protection against mosquito bites, thus providing predictors of insect repellent efficacy. No single electronic property is sufficient to predict repellent efficacy as measured by protection time, rather a set of specific electronic properties is required. Thus, the values of the van der Waals surface electrostatic potential by the amide nitrogen and oxygen atoms, the atomic charge at the amide nitrogen atom, and the dipole moment must all be in optimal ranges for potent repellency. The electronic properties were calculated using the AM semi-empirical quantum chemical method using commercial software. These easily calculable predictors of repellent efficacy should be useful in predicting the relative efficacy of newly designed compounds, thus guiding the selection of new repellents for testing. PMID- 9988313 TI - IgE antibody during infection with the ovine abomasal nematode, Teladorsagia circumcincta: primary and secondary responses in serum and gastric lymph of sheep. AB - A monoclonal antibody to ovine IgE was employed in an ELISA to investigate the IgE antibody responses in serum and gastric lymph to a primary infection of Teladorsagia circumcincta, and following challenge in previously infected sheep. During a primary response, IgE antibody to antigens derived from the infective third stage (L3) and adult (L5) worms were negligible, with low levels of IgE antibody detected in serum and lymph. In contrast, there was a pronounced IgE antibody response in 2/4 sheep to L3 antigens during 2-8 days after challenge of previously infected animals but low levels of IgE antibody to L5 antigens. This response was confirmed in a second but similar experiment, where relatively high levels of IgE antibody was detected to antigens from L3. Antibody levels were higher in lymph than in serum from the same animals, and Western blots of L3 antigen following SDS-PAGE under reducing conditions revealed several bands of MW26-96KD which reacted with the IgE antibody from gastric lymph. Immunohistochemical staining indicated that these IgE antibodies may be reacting with allergens associated with the surface cuticle of the worms. PMID- 9988315 TI - Stimulation of Plasmodium falciparum gametocytogenesis by conditioned medium from parasite cultures. AB - Plasmodium falciparum gametocyte development was examined in erythrocyte monolayer cultures prepared with Cell-Tak, a cell and tissue adhesive. The monolayers, which were stable for up to 10 days in culture, supported multiple cycles of asexual growth and the development of clusters of stage IV gametocytes. Small numbers of chicken erythrocytes incorporated into the monolayers served as internal reference standards for parasite counts. This permitted quantitative assessment of gametocyte formation under different culture conditions. Gametocyte formation was limited in monolayers grown in standard culture medium but it increased slightly in monolayers cocultured with suspensions of parasitized erythrocytes. The number of gametocytes increased significantly in monolayers grown in parasite-conditioned medium. In both cases the changes resulted from increased numbers of stage II and III gametocytes in the monolayers. These results suggest that parasite conditioned medium contains a factor(s) that stimulates sexual development. PMID- 9988316 TI - Application of genetic markers to the identification of recrudescent Plasmodium falciparum infections on the northwestern border of Thailand. AB - Parasite genotyping by the polymerase chain reaction was used to distinguish recrudescent from newly acquired Plasmodium falciparum infections in a Karen population resident on the northwestern border of Thailand where malaria transmission is low (one infection/person/year). Plasmodium falciparum infections were genotyped for allelic variation in three polymorphic antigen loci, merozoite surface proteins-1 and -2 (MSP-1 and -2) and glutamaterich protein (GLURP), before and after antimalarial drug treatment. Population genotype frequencies were measured to provide the baseline information to calculate the probability of a new infection with a different or the same genotype to the initial pretreatment isolate. Overall, 38% of the infections detected following treatment had an identical genotype before and up to 121 days after treatment. These post treatment genotypes were considered recrudescent because of the low (< 5%) probability of repeated occurrence by chance in the same patient. This approach allows studies of antimalarial drug treatment to be conducted in areas of low transmission since recrudescences can be distinguished confidently from newly acquired infections. PMID- 9988317 TI - Linkage of a gene causing malaria refractoriness to Diphenol oxidase-A2 on chromosome 3 of Anopheles gambiae. AB - An inbred line of the African malaria vector Anopheles gambiae is refractory to development of malaria parasites. It is homozygous for a 4.3-kb Sal I restriction fragment at the Dox-A2 locus, whereas the parent population is polymorphic at this locus, and a susceptible line is homozygous for an alternate 3.85-kb fragment. The Dox-A2 locus is located in the middle of chromosome 3R, in division 33B, and is tightly linked to a cluster of genes including Dopa decarboxylase that are involved in the production of melanin. Because the refractoriness phenotype, melanotic encapsulation of ookinete/oocysts, might involve activation of or alteration in one or more of these genes, we performed genetic crosses to determine whether a previously identified Plasmodium cynomolgi Ceylon refractoriness gene, Pif-C, is linked to Dox-A2. Backcross mosquitoes fed on one infected monkey developed infections of < or = 100 oocysts. About 50% of these mosquitoes appeared phenotypically refractory, as expected for the backcross performed, but gave slight evidence of linkage between a refractoriness gene and Dox-A2. In contrast, females fed on a monkey that yielded higher infection levels, up to > 300 oocysts, showed clear evidence of linkage between a refractoriness gene and Dox-A2. We conclude that this Dox-A2-linked refractoriness gene is expressed under conditions particular to the higher infection levels, or that environmental factors obscured the genetic effect of this gene at lower infection levels. PMID- 9988318 TI - Limited genetic diversity of Plasmodium falciparum in field isolates from Honduras. AB - The genetic diversity displayed by Plasmodiumfalciparum field isolates, the occurrence of variant forms of the parasite at different frequencies in different geographic areas, and the complexity of the infections represent major obstacles for the development of effective malaria control measures. However, since most of the existing studies have been performed in regions where P. falciparum transmission is high, little is known about the diversity and complexity of parasite populations circulating in areas of low malaria endemicity. We investigated the extent of genetic polymorphism in P. falciparum field isolates from Honduras, a region where its transmission is low and seasonal. Allelic diversity was analyzed in the highly polymorphic parasite genes encoding the merozoite surface proteins- (MSP-1) and -2 (MSP-2) and the glutamate-rich protein (GLURP) by the polymerase chain reaction. Gene polymorphism was also assessed in the EB200 region derived from the highly size polymorphic Pf332 gene. Limited size polymorphism was detected in all genes analyzed, with four and three variants for the MSP-1 and MSP-2 alleles, respectively, and two size variants for the GLURP and Pf332 genes. Moreover, based on the studied genetic markers, most infections consisted of only a few genetically distinct parasite clones. These results suggest that the P. falciparum parasite populations circulating in this region are genetically homogeneous and point to an association between the extent of parasite genetic diversity and the intensity of malaria transmission. PMID- 9988320 TI - Leishmania spp: completely defined medium without serum and macromolecules (CDM/LP) for the continuous in vitro cultivation of infective promastigote forms. AB - The elimination of serum or of serum-derived macromolecules that supplant the fetal calf serum requirement from Leishmania culture media could decrease costs and improve the feasibility of large-scale production of well-defined parasite material. We report a completely defined medium, without serum-derived protein and/or macromolecules as a serum substitute, of common, available, and inexpensive constituents that can be used in place of serum-supplemented media for the continuous in vitro cultivation of promastigote forms of various Leishmania species. Typical promastigote morphology was observed in Giemsa stained smears, regardless of the strain analyzed. Electrophoretic analysis showed that the proteinase patterns of aserically grown promastigote forms were similar to those obtained in serum-supplemented RPMI 1640 medium for all Leishmania studied. Similar antigenic profiles were recognized in immunoblots by sera from hosts with visceral or cutaneous leishmaniasis after growing promastigotes in the two different culture media. For parasites causing both cutaneous and visceral leishmaniasis, the absence of serum and macromolecules in the culture medium did not markedly change their in vitro infectivity for resident mouse macrophages and their virulence in animals compared with parasites cultivated in nondefined medium. Serum-free technology will be increasingly important in providing stability and reproducibility as research using promastigote moves closer to therapeutic applications. PMID- 9988319 TI - Bacterial expression of a neutralizing mouse monoclonal antibody Fab fragment to a 150-kilodalton surface antigen of Entamoeba histolytica. AB - A mouse monoclonal antibody (MAb) (EH3015, IgG1 with a K light chain) prepared by hybridoma technology recognizes a 150-kD surface antigen of Entamoeba histolytica and inhibits adherence and cytotoxicity of the ameba to mammalian cells. The genes encoding the light chain and the Fd region of the heavy chain of the MAb were cloned and expressed in Escherichia coli. The plasmid used was designed for the expression of Fab with a hexa-histidine tag in the periplasmic space. Recombinant Fab fragments were purified and analyzed by an indirect immunofluorescence antibody test and Western immunoblot. The specificity of the recombinant Fab fragment was comparable with the parent whole IgG. In addition, the Fab fragments significantly inhibited the adherence of E. histolytica to erythrocytes. These results suggest that the production of a neutralizing MAb in Escherichia coli is practical and efficient with this expression system. PMID- 9988321 TI - Infection of sand flies by humans coinfected with Leishmania infantum and human immunodeficiency virus. AB - To determine the role that Leishmania infantum/human immunodeficiency virus (HIV) coinfected patients could play in the epidemiology of visceral leishmaniasis (VL), we applied direct xenodiagnosis of VL in this study to test the infectivity of six coinfected patients to colonized Phlebotomus perniciosus. All patients proved to be infective for the sand flies. The infectivity of patients who had still not received specific treatment for VL was inversely proportional to their absolute CD4+ T lymphocyte cell count. It has been proven that P. perniciosus can acquire and allow the development of L. infantum by feeding on L. infantum/HIV coinfected patients. Since this sand fly is an important vector of VL in southern Europe, a new natural anthroponotic cycle could be considered in the epidemiology of L. infantum/HIV coinfection. The design of leishmaniasis control programs and the management of coinfected individuals should take these findings into account. PMID- 9988322 TI - Short report epidemiologic studies on cutaneous leishmaniasis in eastern Panama. AB - The Panamanian Ministry of Health, through the Interamerican Development Bank, contracted the Gorgas Memorial Laboratory to conduct epidemiologic studies on leishmaniasis and malaria in eastern Panama from July 1984 through June 1985. Preliminary results of the biomedical and entomologic teams investigating the epidemiology of cutaneous leishmaniasis in the eastern part of the country are presented in this short report. The principal findings of the study revealed 1) a large disparity in the incidence and prevalence of the disease among the five communities investigated; 2) the appearance of self-cures without the benefit of effective treatment; 3) a relatively high percentage of subclinical cases; and 4) determination of the sandfly vector species for each community. Also reported here is a case of a double infection with two distinct species of Leishmania, L. mexicana and L. amazonensis, in a single individual. PMID- 9988323 TI - Human granulocytic ehrlichiosis in Bulgaria. AB - Human granulocytic ehrlichiosis (HGE) is a recently described rickettsiosis in the United States transmitted by Ixodes species ticks. In Europe, only a few studies on HGE exist. Two hundred Bulgarian patients with tick bites and 70 healthy blood donors were tested for HGE using an immunofluorescence assay with the HGE agent as an antigen. Elevated antibody titers (> or = 1:80) were found in 14 (9.7 %) of 145 patients with erythema migrans, two (8%) of 25 tick-exposed patients with lymphadenopathy only, one (20%) of five patients with tick bite with fever, chills, and headache, one (4%) of 25 healthy tick-exposed patients, and two (2.9%) of 70 blood donors. These results show for the first time that HGE is probably common in southeastern Europe. The study provides evidence of coinfection or concurrent infection of patients with Lyme disease and HGE, thus supporting the possible role of I. ricinus for transmitting the HGE agent. PMID- 9988324 TI - Detection of the agents of human ehrlichioses in ixodid ticks from California. AB - A study was conducted in northern California to estimate the prevalence and distribution in ixodid ticks of the rickettsial agents of human monocytic (HME) and human granulocytic (HGE) ehrlichioses. More than 650 ixodid ticks were collected from 17 sites in six California counties over a 15-month period. Ehrlichia chaffeensis, the causative agent of HME, was detected by a nested polymerase chain reaction (PCR) in Ixodes pacificus (minimum infection rate [MIR] = 13.3%) and Dermacentor variabilis (infection rate=20.0%) from a municipal park in Santa Cruz County. The HGE agent was detected by nested PCR in I. pacificus adults from a heavily used recreational area in Alameda County (MIR = 4.7%) and a semirural community in Sonoma County (MIR = 6.7%). Evidence of infection with Ehrlichia spp. was not detected in D. occidentalis adults or I. pacificus nymphs. This study represents the first detection of E. chaffeensis in California ticks and the first report of infection in Ixodes spp. The competency of I. pacificus to be coinfected with and to transmit multiple disease agents, including those of human ehrlichioses and Lyme disease, has yet to be determined. PMID- 9988325 TI - Trichinellosis in the United States, 1991-1996: declining but not gone. AB - Since the U.S. Public Health Service began recording statistics on trichinellosis in 1947, the number of cases reported by state health departments has decreased steadily. In the late 1940s, health departments reported an average of 400 cases and 10-15 deaths each year. From 1991 to 1996, the period covered in this report, three deaths in 230 cases were reported to the Centers for Disease Control and Prevention (an average of 38 cases per year), including 14 multiple case outbreaks from 31 states and Washington, DC. Information on the suspected food item was available for 134 (58%) of the 230 reported cases. Pork was implicated in 80 (60%) cases, bear meat in 31 (23%), walrus meat in 13 (10%), and cougar meat in 10 (7%). Sausage was the most frequently implicated pork product (i.e., 57 of the 64 cases for which the form of the pork product was identified). The proportion of trichinellosis cases attributable to consumption of commercial pork continued to decrease; this decrease was probably due to a combination of factors, including the continued reduction in the prevalence of Trichinella spiralis in domestic swine, the increased use of home freezers, and the practice of thoroughly cooking pork. As a proportion of all cases reported, those associated with wild game meat products has increased; however, the absolute numbers of such cases have remained similar at approximately 9-12 per year. The continued multiple case outbreaks and the identification of nonpork sources of infection indicate the need for further education and control measures. PMID- 9988326 TI - Case-control study of seropositivity for cysticercosis in Cuenca, Ecuador. AB - The prevalence of neurocysticercosis has been well documented in rural communities in Latin America using the enzyme-linked inmmunoelectrotransfer blot (EITB) assay. We studied the prevalence of neurocysticercosis in an urban, upper middle class population in Cuenca, Ecuador. Family members of 34 index cases with parenchymal neurocysticercosis on a computed tomography (CT) scan and family members of 14 patients who had normal CT scans after a trauma or migraine were enrolled in the study. Serum was obtained from 226 individuals, 173 (72%) from the case families and 67 (28%) from the control families. Twelve percent of the case family members and 4% of the control family members were seropositive by the EITB assay. This was a statistically significant difference (P < 0.05) when age and education were held constant by logistic regression. Seropositivity was not related to age. No neurologic symptom proved predictive of serostatus and the only demographic variable that correlated with seropositivity was increased crowding. Positive serology in index cases did correlate with CT findings as follows: 86% of patients with active lesions, 67% with transitional lesions, and only 41% of patients with inactive lesions were positive by the EITB assay. Eighteen percent of family members with a positive EITB test result had parenchymal lesions on a subsequent CT scan. This study demonstrates a high rate of seropositivity of cysticercosis among urban, middle to upper-middle class individuals in a region endemic for Taenia solium. Household contacts of patients with neurocysticercosis had a three-fold higher risk of positive serology for cysticercosis, in comparison with controls. PMID- 9988327 TI - Hantavirus (Bunyaviridae) infections in rodents from Orange and San Diego counties, California. AB - During a screening program to determine the extent of hantavirus activity in Orange and San Diego Counties, California, serum samples from 2,365 rodents representing nine genera and 15 species were tested for hantavirus antibodies. A reverse transcription-polymerase chain reaction on selected seropositive rodents was used to identify the specific hantavirus. Rodents positive for Sin Nombre virus (SNV) antibodies by Western blot included 86 (9.1%) of 948 deer mice (Peromyscus maniculatus), four (1.5%) of 275 California mice (Peromyscus californicus), one (0.5%) of 196 cactus mice (Peromyscus eremicus), 51 (12.2%) of 417 harvest mice (Reithrodontomys megalotis), and five (12.5%) of 40 California voles (Microtus californicus). All other specimens tested were negative for hantavirus antibodies. There was a correlation between age and sex of the reservoir host and prevalence of SNV antibody, especially among male deer mice and harvest mice. Few seasonal trends in antibody prevalence were observed and continued maintenance of SNV and El Moro Canyon virus was found at several foci over a 4-5-year period. Isla Vista virus was also found in voles and represents the first recorded in Orange County. Microhabitat selection on the part of these rodents based on plant density, plant height, and availability of food plants may explain, to some extent, all of the hantavirus-positive foci throughout the study area over a broad geographic range and the lack of antibody-positive rodents in dense chaparral, woodland, and riparian areas. The majority of rodents positive for SNV was identified from localities along coastal bluffs and the foothills of the Santa Ana Mountains, where trap success was high and P. maniculatus represented 43% of all rodents collected. Several residential, commercial, and industrial sites exist in these areas and the potential health risk should not be overlooked. This study represents an in-depth analysis of the prevalence, host distribution, and characteristics of rodent populations infected by three hantaviruses within a small, well-defined, geographic area. PMID- 9988328 TI - Proinflammatory cytokines and elastase-alpha-1-antitrypsin in Argentine hemorrhagic fever. AB - Argentine hemorrhagic fever (AHF) is a disease caused by Junin virus. In the acute phase, patients present hematologic and neurologic involvement with high levels of interferon-alpha and tumor necrosis factor-alpha (TNF-alpha. Nineteen patients with a confirmed diagnosis of AHF were studied: six severe, four moderate and nine mild cases. Serum levels of interleukin-6 (IL-6), IL-6 soluble receptor (IL-6sR), IL-8, IL-10, and elastase-alpha1-antitrypsin complex (E-alpha 1AT) were assayed by ELISAs. Levels of IL-6, IL-8, and IL-10 were high in nine, 12, and 13 patients, respectively, while levels of IL-6sR were high in two patients and low in one patient. Seven patients had increased levels of E alpha1AT. Significant correlations were found between levels of both IL-8 and IL 10 with those of TNF-alpha as well as between IL-8 and E-alpha 1AT. These data demonstrate activation of pro-inflammatory and anti-inflammatory cytokine pathways, and statistical analysis showed differences among the clinical forms of illness. This study shows that IL-8 plays an essential role in neutrophil activation in AHF patients as demonstrated in other infectious diseases. PMID- 9988329 TI - Attachment of Burkholderia pseudomallei to pharyngeal epithelial cells: a highly pathogenic bacteria with low attachment ability. AB - Respiratory infections are initiated by the attachment of bacteria to pharyngeal epithelial cells. We studied the attachment of Burkholderia pseudomallei to pharyngeal epithelial cells. After one, two, three, and four washes, there were 22.6+/-8.9, 15.7+/-7.0, 6.8+/-3.1, and 4.6+/-1.1 (mean+/-SD) attached bacteria/cell, respectively. If the bacterial concentration was maintained at 1 X 10(8) colony-forming units (cfu)/ml and three washes were done, at concentrations of 2.5 x 10(4), 5 X 10(4), and 1 x 10(5) cells/ml there were 9.9+/-3.6, 3.3+/ 0.8, and 2.5+/-1.1 attached bacteria/cell, respectively. If the cell concentration was kept at 2.5 x 10(4) cells/ml and three washes were done, at bacterial concentrations of 1 x 10(5), 1 X 10(6), 1 X 10(7), 1 x 10(8), and 1 x 10(9) cfu/ml, there were 0.3+/-0.3, 0.6+/-0.6, 1.0+/-0.2, 5.1+/-2.3, and 9.6+/ 1.9 attached bacteria/cell, respectively. There were 4.8+/-1.9, 5.5+/-2.5, 5.6+/ 1.9, and 6.4+/-2.6 attached bacteria/cell at 0, 30, 120, and 240 min of incubation, respectively. Pharyngeal cells from 10 persons (seven men and three women, mean+/-SD age = 30.7+/-8.1 years, 12 experiments with a single isolate) showed that there were 7.8+/-4.3 attached bacteria/cell. It was found that the efficiency of attachment of this bacteria was very low (7.0+/-3.3 bacteria/cell). Electron microscopy revealed that there were no fimbriae but a thin capsular polysaccharide layer on the surface of B. pseudomallei. Attachment to pharyngeal epithelial cells appeared to be mediated by this structure. PMID- 9988330 TI - Detection of light subunit neurofilament and glial fibrillary acidic protein in cerebrospinal fluid of Trypanosoma brucei gambiense-infected patients. AB - Light subunit neurofilament (NFL) and glial fibrillary acidic protein (GFAP) concentrations were determined in cerebrospinal fluid (CSF) of 34 patients with human African trypanosomiasis (HAT), five serologically positive but parasitologically unconfirmed individuals, and four healthy controls without evidence of HAT. In patients with second stage HAT (n = 30), NFL levels were abnormally elevated in 10 cases and GFAP levels in five. The astrogliosis observed in HAT and experimental models of HAT is confirmed in our study by the presence of increased GFAP levels in the CSE The abnormal NFL CSF levels reflect structural damage of nerve cells in 33 % of the second-stage patients studied. To our knowledge, this is the first time neuronal damage in HAT patients is demonstrated by using biochemical markers of brain damage in the CSF. PMID- 9988331 TI - Low levels of fibrin-stabilizing factor (factor XIII) in human Plasmodium falciparum malaria: correlation with clinical severity. AB - Plasmodium falciparum malaria is associated with procoagulant activity but not with thromboembolism. We measured coagulation factor XIII, i.e., fibrin stabilizing factor, in 45 patients with falciparum malaria over time. Of these, 22 had organ complications. The factor XIII antigen (subunits A and B) and plasma activity levels were abnormally low in those with falciparum malaria. They increased during antiparasitic therapy. In 14 of 22 patients with complications, but in no patient with mild disease (P < 0.001), subunit A and activity was < 50%. The factor X.III levels were inversely correlated with clinical severity, parasitemia, and human neutrophil elastase (HNE), but not with thrombin antithrombin III levels. Thus, low factor XIII levels may reflect proteolysis by HNE, rather than procoagulant activity. One could speculate that factor XIII degradation in severe malaria prevents thromboembolism. On the other hand, factor XIII deficiency might reduce protection of the vascular endothelium against HNE and reactive oxygen species, which would promote organ damage. PMID- 9988332 TI - In vitro susceptibility of African isolates of Plasmodium falciparum from Gabon to pyronaridine. AB - The in vitro activity of pyronaridine was evaluated against 62 isolates of Plasmodium falciparum from Libreville, Gabon using an isotopic, drug susceptibility microtest and was compared with amodiaquine, chloroquine, quinine, and halofantrine activities. The mean 50% inhibitory concentration (IC50) values of the 62 isolates from Gabon to pyronaridine was 3.0 nM (95% confidence interval [CI] = 2.1-3.9). Pyronaridine was less potent against chloroquine-resistant isolates than chloroquine-susceptible isolates but more potent than chloroquine against chloroquine-resistant parasites. The cut-off value for in vitro reduced susceptibility to pyronaridine was an IC50 > 15 nM. Two isolates (3%) showed an IC50 > 15 nM. A significant positive correlation was found between the activities of pyronaridine and chloroquine (r2 = 0.26, P < 0.001), pyronaridine and quinine (r2 = 0.36, P < 0.001), pyronaridine and amodiaquine (r2 = 0.55, P < 0.001), and pyronaridine and halofantrine (r2 = 0.50, P < 0.001). This correlation suggests in vitro cross-resistance or at least in vitro cross-susceptibility, which is not necessarily predictive of cross-resistance in vivo. The present in vitro findings require comparison with those of clinical studies. PMID- 9988333 TI - Immunocapture diagnostic assays for malaria using Plasmodium lactate dehydrogenase (pLDH). AB - We have developed two diagnostic assays based on the specific detection of Plasmodium lactate dehydrogenase (pLDH) activity. These assays exploit a panel of monoclonal antibodies that capture the parasite enzyme and allow for the quantitation and speciation of human malaria infections. An immunocapture pLDH activity assay (ICpLDH) allows for the rapid purification and measurement of pLDH from infected blood using the NAD analog APAD, which reacts specifically with Plasmodium LDH isoforms. An immunochromatographic test (the OptiMAL assay) was also formatted and allowed the detection of parasite infections of approximately 200 parasites/microl of blood. By using a combination of antibodies, both tests can not only detect but differentiate between P. falciparum and non-P. falciparum malaria. Both assays show a sensitivity comparable with other commercial nonmicroscopic tests; importantly, we found very few instances of false-positive samples, especially with samples from patients recently cleared of malaria infection. Furthermore, we find that when one uses the quantitative ICpLDH assay, the levels of pLDH activity closely mirror the levels of parasitemia in both initial diagnosis and while following patient therapy. We conclude that diagnostic tests based on the detection of pLDH are both sensitive and practical for the detection, speciation, and quantitation of all human Plasmodium infections and can also be used to indicate drug-resistant infections. PMID- 9988334 TI - Ultrasonography as an aid to diagnosis and treatment in a rural African hospital: a prospective study of 1,119 cases. AB - The aim of this study was to assess the utility of ultrasonography in a rural African hospital in Cameroon with scarce resources. A prospective questionnaire was administered and completed for each of the 1,119 consecutive cases included in the study. Among these 1,119 cases, the diagnosis made by clinicians and by echography could be verified by another means for 323 patients. Ultrasonography showed abnormal findings in 78% of the cases. In the group of 323 patients in which the diagnosis made by echography could be verified, it was correct in 95.4% of the cases, erroneous in 4.6% of the cases, judged useful for diagnosis in 67.8% of the cases, and not contributive in 27.6% of the cases. Ultrasonography was judged useful when treatment was decided upon in 62% of the cases. This study demonstrated the value of ultrasonography in the context of a developing country and the conditions by which its use could be delineated. PMID- 9988335 TI - Pool screen polymerase chain reaction for estimating the prevalence of Onchocerca volvulus infection in Simulium damnosum sensu lato: results of a field trial in an area subject to successful vector control. AB - Detection of infective parasites in the vector population can be an early indicator of recrudescence in areas freed of new cases of onchocerciasis. However, dissection of vector black flies is inefficient in areas subject to effective control. Recently, a polymerase chain reaction (PCR)-based assay has been used to detect a single Onchocerca volvulus-infected black fly in pools containing large numbers of uninfected flies. This method had not been validated on wild-caught black flies in an area subject to effective vector control. Here, we report a method of restricting the pool screen PCR assay to infectious parasites and the results of a field test in an area subject to long-term vector control. The prevalence of infection determined by dissection did not differ from that determined by pool screen PCR. The results suggest that the PCR assay may be a useful tool for epidemiologic surveillance for 0. volvulus infection. PMID- 9988336 TI - Operational validation of the direct agglutination test for diagnosis of visceral leishmaniasis. AB - The validity of the direct agglutination test (DAT) for visceral leishmaniasis (VL) was studied with a standardized field kit on 148 clinically suspected persons and 176 healthy controls recruited between 1993 and 1994 from an endemic area in Gedaref State, Sudan. A sensitivity of 95.9% and a specificity of 99.4% were found at a 1: 8,000 cut-off titer when parasitologically confirmed cases were compared with healthy controls. While corroborating previously reported sensitivity and specificity estimates of this serodiagnostic test, this study examined the bias generated by commonly used test validation procedures. The fundamental methodologic problem in VL test validation is the absence of a reliable gold standard. Moreover, any operational guideline on DAT use has to consider the critical dependency of the predictive values of the test on VL prevalence rates. The DAT diagnostic cut-off titer depends upon many external factors, among which the prevalence of disease in the area and the case mix seem the most important. PMID- 9988337 TI - Differential effect and interaction of monocytes, hyperimmune sera, and immunoglobulin G on the growth of asexual stage Plasmodium falciparum parasites. AB - Using a flow cytometry-based parasite growth inhibition assay (GIA) and an antibody-dependent cellular inhibition (ADCI) assay, we have assessed the differential effect and interaction of monocytes, immune sera, and purified immunoglobulins from Kenyan adults on the growth of Plasmodium falciparum parasites in vitro. We found that monocytes from 14 different normal, healthy, non-malaria-exposed donors had varying effects on parasite growth, i.e., inhibition or enhancement of parasitemia, suggesting heterogeneity in anti parasitic activities of monocytes from individual donors. Twenty-two serum samples collected from clinically immune adults from western Kenya inhibited growth of P. falciparum after 48 hr in culture. In contrast, all IgG preparations, except one, purified from the same serum samples enhanced parasite growth. In ADCI experiments, of the 22 purified IgG samples used, 11 showed ADCI activities with specific growth inhibition (SGI) of more than 10%, with the highest at 27.6%, and the remaining 11 IgG samples had an SGI of less than 10%. Our results also showed that the ratio of IgG1 to IgG3 antibodies, as determined by an indirect immunofluorescence assay, was higher in the high ADCI response group than in the low response group, suggesting that a higher concentration of IgG1 antibodies with a higher IgG1/IgG3 ratio might be associated with ADCI activities. The present study has resulted in the development of simple, reproducible flow cytometry-based GIA and ADCI assays, and also provides baseline information for further investigation of the role of ADCI activity in naturally acquired immune protection against malaria. PMID- 9988338 TI - In vitro production of type 1 and type 2 cytokines by peripheral blood mononuclear cells from subjects coinfected with human immunodeficiency virus and Leishmania infantum. AB - To explore the type 1 and type 2 cytokine profile in cases coinfected with human immunodeficiency virus (HIV) and Leishmania infantum, production of interleukin-4 (IL-4), interleukin-10 (IL-10), interferon-gamma (IFN-gamma), and interleukin-2 receptor (IL-2R) was investigated in mitogen-stimulated and unstimulated peripheral blood mononuclear cell cultures from eight HIV/Leishmania coinfected subjects matched with eight anti-HIV-positive subjects with no evidence of Leishmania coinfection. Levels of IL-4 and IL-2R increased significantly from the baseline levels in the peripheral blood mononuclear cell supernatants of HIV/Leishmania coinfected subjects following stimulation with phytohemoagglutin, whereas the postchallenge concentration of IFN-gamma was significantly increased in the HIV-infected group. The levels of IL-4 and IL-10 were significantly higher in the HIV/Leishmania group throughout evaluation. Post-stimulation IFN-gamma production was significantly higher in the HIV-positive group in comparison with that of the HIV-Leishmania coinfected subjects. These observations support the notion that a Th2 cytokine response is present during a Leishmania infection, even among HIV-coinfected individuals. PMID- 9988339 TI - Strongyloides stercoralis hyperinfection associated with human T cell lymphotropic virus type-1 infection in Peru. AB - A study was conducted in Lima, Peru to determine if patients with Strongyloides hyperinfection had human T cell lymphotropic virus type-1 (HTLV-I) infection. The study included patients with Strongyloides hyperinfection and a control group consisted of sex- and age-matched asymptomatic healthy individuals whose stools were negative for Strongyloides. A third group included patients with intestinal strongyloidiasis. Sera from each study subject were tested for HTLV-1/2I by an ELISA and Western blot. The HLTV-1 infection rates (85.7%, 18 of 21) were significantly (P < 0.001) associated with Strongyloides hyperinfection compared with the control group (4.7%, 1 of 21). The HTLV-1 rate (10%, 6 of 62) for patients with intestinal strongyloidiasis was significantly (P < 0.001) lower than patients with Strongyloides hyperinfection, but did not differ significantly (P > 0.05) from the control group. The association of HTLV-1 infection was observed among 17 of 19 patients more than 20 years of age and one of two younger patients. None had HTLV-2 infection. In conclusion, Strongyloides hyperinfection among Peruvian patients was highly associated with HTLV-1 infection. PMID- 9988340 TI - Isolation of Fusobacterium necrophorum from cancrum oris (noma). AB - A study of the predominant microflora in active sites of noma (cancrum oris) lesions was carried out in eight noma patients 3-15 years of age in Sokoto State in northwestern Nigeria. Paper point sampling and conventional anaerobic microbiologic techniques were used. Fusobacterium necrophorum was recovered from 87.5% of the noma lesions. Oral microorganisms included Prevotella intermedia, alpha-hemolytic streptococci, and Actinomyces spp. which were isolated from 75.0%, 50.0%, and 37.5% of the patients, respectively. Peptostreptococcus micros, Veillonella parvula, Staphylococcus aureus, and Pseudomonas spp. were each recovered from one lesion. The F. necrophorum and P. intermedia isolates were tested for antibiotic sensitivity to clindamycin, tetracycline, metronidazole, and penicillin using the E-test, and all strains were observed to be sensitive to all of the antibiotics tested with the exception of one strain of P. intermedia, which showed resistance to penicillin. The first reported isolation from human noma lesions of F. necrophorum, a pathogen primarily associated with animal diseases, may have important etiologic and animal transmission implications. PMID- 9988341 TI - Infectivity of Cryptosporidium parvum in healthy adults with pre-existing anti-C. parvum serum immunoglobulin G. AB - A 50% infectious dose (ID50) of 132 Cryptosporidium parvum oocysts was previously determined in serologically negative individuals (ELISA). In this study, 17 healthy adults with pre-existing anti-C. parvum serum IgG were challenged with 500-50,000 oocysts. Infection and diarrhea were associated with the higher challenge doses. The ID50 was 1,880 oocysts, > 20-fold higher than in seronegative volunteers. Fecal oocysts were detected in only seven (53.8%) of 13 individuals with clinical cryptosporidiosis, indicating that the host response may effectively decrease the number of oocysts produced. Subjects with the highest absorbances prior to challenge had little to no increase in IgG following challenge, whereas volunteers with lower reactivities showed significant postchallenge increases. This suggests that an upper limit of serum IgG was present in some subjects, while others were further stimulated by an additional exposure. These data indicate that prior exposure to C. parvum provides protection from infection and illness at low oocyst doses. PMID- 9988342 TI - Fecal occult blood testing on Trichuris-infected primary school children in northeastern peninsular Malaysia. AB - Stool specimens of 104 primary schoolchildren (mean+/-SD age = 8.2+/-0.3 years) were examined for helminth eggs and for occult blood to investigate the possibility that trichuriasis causes occult intestinal bleeding in the absence of the overt Trichuris dysentery syndrome. A commercially available guaiac test was used to detect fecal occult blood. Sixty-one children had Trichuris infection, 11 of whom had heavy infections (> 10,000 eggs per gram of feces [epg]), and 53 had Ascaris infections. No hookworm infection was detected. Baseline screening yielded only one weakly positive occult blood test result in a child with a light (800 epg) Trichuris infection. Serial stool occult blood testing on the 11 subjects with heavy trichuriasis and 8 uninfected controls yielded a single weakly positive result in the control group. The results provide no evidence that trichuriasis predisposes to significant occult gastrointestinal bleeding in children in the absence of the dysenteric syndrome. PMID- 9988343 TI - Management of childhood diarrhea and use of oral rehydration salts in a suburban West African community. AB - In a household survey in Guinea-Bissau, 319 episodes of diarrhea in children were followed by interviews every second day with the aim of investigating perceived morbidity and subsequent actions taken. The majority of the mothers had good knowledge of oral rehydration salts (ORS). However, only 58% of the episodes were treated with ORS and the amount given was insufficient. Mothers with no knowledge of ORS did not use it during the observed attack of diarrhea regardless of contact with a health center, which suggests that maternal knowledge is an important determinant of whether health personnel provide ORS. Children with diarrhea considered to be caused by teething were less likely to receive ORS in the acute phase (risk ratio = 0.6, 95% confidence interval [CI] = 0.5-0.9). Univariate analyses showed that the use of ORS was related to number of reported symptoms, the mother being the care taker, consultations, previous use of ORS, good knowledge of ORS, and having ORS sachets at home. Multivariate Cox regression analyses showed that the presence of ORS sachets at home at the onset of diarrhea was the strongest predictor of use (hazard ratio = 3.3, 95% CI = 1.9 3.6). Improved health education should focus more on the quantity of ORS needed, early signs of dehydration, treatment of teething diarrhea, and breast feeding, and address mothers who have no prior knowledge of ORS. Management of diarrhea may be improved by a more liberal distribution of ORS sachets. PMID- 9988344 TI - Flow cytometric analysis of DNA content of living and fixed cells: a comparative study using various fixatives. AB - The majority of studies dealing with DNA analyses are made on fixed cells. In this context, the efficiency as fixatives of ethanol, methanol, acetone, Carnoy, Boehm-Sprenger and aldehydes was determined using two different DNA fluorescent probes, Hoechst 33342 and propidium iodide. The purpose of our study was to find the fixative that would provide the best results with respect to the following parameters: aggregates, cell size and granularity, and DNA staining analysis. Using murine fibroblasts, we found that 68% ethanol, 85% methanol and aldehydes did not increase aggregate formation, whereas Carnoy, acetone or Boehm-Sprenger fixatives did. The results show that aldehydes seem to alter cell size least. All fixatives induce an increase in cell granularity, which is very pronounced with alcohols, but aldehydes alter morphology less than alcohols. We observed that the fixatives giving the best resolution with Hoechst 33342 staining lead to a lower measurement variability than with propidium iodide staining. This study leads us to conclude that 68% ethanol and 85% methanol can be considered as appropriate fixatives for flow cytometry studies of DNA content. PMID- 9988345 TI - Immunohistochemical video-microdensitometry of myocardial collagen type I and type III. AB - Collagen is an essential part of the cardiac interstitium. Collagen subtypes, their location, total amount and the architecture of the fibrillar network are of functional importance. Architecture in terms of density of the fibrillar network is assumed to be reflected by the intensity of immunohistochemical staining of collagen. The aim of this study was to evaluate a video-based microdensitometric method for quantifying density expressed as absorbance of collagen subtypes I and III stained with an indirect immunoperoxidase method in myectomy specimens of patients with hypertrophic obstructive cardiomyopathy. Various factors influencing the immunohistochemical staining product and the technical properties of the image analysis system were investigated. Linearity between collagen concentration and the absorbance of the immunohistochemical staining product was demonstrated for collagen I using a dot-blot technique. Immunohistochemical collagen staining and density measurement were easily reproducible. The cardiac disability of the patients was assessed according to the New York Heart Association (NYHA) criteria. There was a significant increase in collagen type I density with higher NYHA class, whereas no significant association was found for total collagen area fraction. Thus, video-based microdensitometry gives further insight into the structural remodelling of myocardial collagens and reveals their significance in the process of heart failure in hypertrophic cardiomyopathy. PMID- 9988346 TI - Investigation of tissue preparation conditions for non-radioactive in situ hybridization: localization of transforming growth factor-alpha message in rat kidney. AB - A non-radioactive method of in situ hybridization was used to localize transforming growth factor-alpha mRNA in epithelial cells of collecting ducts and tubules in rat kidney tissue sections. The intensity and specificity of staining were assessed under a variety of tissue preparation conditions, including a direct comparison of paraffin against frozen sections. Under optimal conditions, both the signal strength and the cellular localization of the growth factor message were superior in paraffin sections. The staining method could also be used to localize the message in lung tissue, indicating that the procedure is generally applicable to other tissues. Our results indicate that the use of paraffin sections for nonradioactive in situ hybridization affords a number of advantages for the localization of specific messages in tissue sections. PMID- 9988347 TI - Location and distribution of non-collagenous matrix proteins in musculoskeletal tissues of rat. AB - The study assessed immunohistochemically the location and distribution of various non-collagenous matrix proteins (fibronectin, laminin, tenascin-C, osteocalcin, thrombospondin-1, vitronectin and undulin) in musculoskeletal tissues of rat. Fibronectin and thrombospondin-1 were found to be ubiquitous in the studied tissues. High immunoreactivity of these proteins was found in the extracellular matrix of the anatomical sites where firm bindings are needed, i.e. between muscle fibres and fibre bundles, between the collagen fibres of a tendon and at myotendinous junctions, osteotendinous junctions and articular cartilage. Tenascin-C was found in the extracellular matrix of regions where especially high forces are transmitted from one tissue component to the other, such as myotendinous junctions and osteotendinous junctions. Laminin was demonstrated in the basement membranes of the muscle cells and capillaries of the muscle-tendon units. Osteocalcin immunoreactivity concentrated in the extracellular matrix of areas of newly formed bone tissue, i.e. in the subperiosteal and subchondral regions, osteoid tissue and mineralized fibrocartilage zone of the osteotendinous junction. Mild vitronectin activity could be seen in the extracellular matrix of the osteotendinous and myotendinous junctions, and high activity around the bone marrow cells. Undulin could be demonstrated in the extracellular matrix (i.e. on the collagen fibres) of the tendon and epimysium only. However, it was co distributed with fibronectin and tenascin-C. Together, these findings on the normal location and distribution of these non-collagenous proteins in the musculoskeletal tissues help to form the basis of knowledge against which the location and distribution of the these proteins in various pathological processes could be compared. PMID- 9988348 TI - Transient increase in the alpha3-isoform of Na,K-ATPase in rat erythroblastic cells. AB - Using immunoelectron microscopy and isoform-specific antibodies against Na,K ATPase to study changes in Na,K-ATPase in rat erythroblastic cells during maturation, we unexpectedly observed numerous antigenic sites against the alpha3 isoform in the cytoplasmic phase. There was an increase in the number of alpha3 isoforms after denucleation of the erythroblast. The increase was transient. As the reticulocyte matured into a red blood cell, the number of alpha3-isoforms was reduced drastically. This alpha3-isoform was distributed in a reticular pattern resembling the double layers of endoplasmic reticulum. Western blot analysis confirms the presence of the alpha3-isoform in these cells. X-ray microanalysis of the erythroid series of cells in the bone marrow shows that sodium concentration in the young reticulocyte is higher than that in the nucleated erythroblast. The reason for the transient increase in this pump protein is not clear. It is possible that the increase in sodium concentration in the reticulocyte plays a role in the increase in pump protein synthesis. PMID- 9988349 TI - Glycoconjugate expression during early mouse oculogenesis. AB - The carbohydrate side-chain of glycoconjugates can show a developmentally regulated expression pattern. In order to analyse these changes during the development of the eye, 13 lectins were used to reveal glycoconjugates histochemically in 8.5- to 14-day-old mouse embryos. During this period, eyes develop from the most immature vesiculation of the neural plate neuroepithelium into a primitive stage with all structures present, such as pigment epithelium, not yet differentiated neuroretina and lens. A striking diversity of carbohydrate side-chain expression was observed in the preocular somatoectoderm and neural plate of 8.5-day-old embryos, as indicated by the binding of nine different lectins. Binding sites at the apical poles of neuroepithelium of five of these lectins (PNA, LCA, SBA, LPA and GSA-II) disappeared completely during further development. The binding sites of four other lectins, WGA, MPA, Con A and BPA, remained expressed during the course of development, being indicative for the carbohydrate side-chains beta-GlcNAc(1-4)Gluc, alpha-Gal(1-3)GalNAc, alpha-D Man/alpha-D-Gluc and alpha-GalNAc. In contrast, binding sites for GSA-I, RCA-I (alpha-D-Gal), UEA-I (alpha-L-Fuc) and DBA (alpha-GalNAc(1-3)GalNAc) were not present at any developmental stage. The time point of gross changes of lectin binding sites correlates well with the period of neural tube formation. During later development from neuroectoderm to the ocular pigment epithelium, a sharp reduction in all lectin binding sites at the apical cell poles, except for WGA and MPA, was observed. WGA binding sites were present until embryonic day 10, while those for MPA were present until day 9. At the basal cell poles of the pigment epithelium, all lectin binding sites except for WGA were lost after embryonic day 11.5. These results indicate that there are sophisticated kinetics of glycoconjugate expression during the course of early embryonic development of ectoderm into its descendent tissues. PMID- 9988350 TI - Abstracts of papers presented at a Symposium on the theme 'Progress in Basic, Applied and Diagnostic Histochemistry'. Prague, 10-12 December 1997. PMID- 9988351 TI - Dialysis hypotension. PMID- 9988352 TI - Dialysis hypotension and splanchnic circulation. PMID- 9988353 TI - Daily hemofiltration in severe heart failure. PMID- 9988354 TI - Liver assist systems: state of the art. AB - Attempts to develop liver support systems for the treatment of patients with liver failure have ranged from use of plasma exchange to utilization of charcoal columns and extracorporeal devices loaded with liver tissue. However, no system has achieved wide clinical use and - in the absence of liver transplantation - severe hepatic failure continues to be associated with significant morbidity and mortality. In this paper, the authors review the current status of liver assist systems and summarize their clinical experience with a xenogeneic cell based bioartificial liver. PMID- 9988355 TI - Symptoms in hemodialysis patients and their relationship with biochemical and demographic parameters. AB - Symptoms can markedly influence the hemodialysis patients well-being and quality of life. The aim of this paper is to study the frequency of symptoms at home and how these relate to biochemical and treatment variables. Seventy-three hemodialysis patients were questioned on the absence, occasional presence or daily recurrence (score = 0, 1, 2) of 14 symptoms and a record was made of their biochemical parameters, age, time on treatment and KtIV as a function of each symptom. The following relationships were detected: thirst with high Osm and BUN; asthenia with old age and hypoalbuminemia; insomnia with hypercalcemia; hypersomnia with hypoxemia and hypernatremia; anorexia with hypokalemia; dyspnea with old age, hypernatremia and hypokalemia; dysgeusia with hypoxemia; nausea with alkalemia, hypoxemia and low BUN; vomiting with alkalemia. Pruritus, arthralgia, restless legs syndrome, cramp and tremor showed no relationships. Monitoring acid-base balance and plasma electrolytes could help to alleviate symptoms and ameliorate quality of life of hemodialysis patients. PMID- 9988356 TI - Intradialytic hypotension in relation to pre-existent autonomic dysfunction in hemodialysis patients. AB - After having monitored haemodynamics during haemodialysis, we examined autonomic nervous function in rest prior to a next dialysis session in 28 patients on chronic intermittent haemodialysis. The aim was to compare intradialytically hypotensive with stable patients to assess whether blood pressure regulating mechanisms were related to basal autonomic function, assessed as heart rate variability (HRV) tested by means of the deep breathing test, the lying-to standing test, and the Valsalva maneuver. Impedance cardiography was used to determine stroke volume and cardiac output during dialysis. In addition, blood pressure was registered automatically and systemic vascular resistance calculated. Blood volume variation was monitored by an on-line optical device. Intradialytic hypotension was observed in 10 patients (36%). Systemic vascular resistance in hypotensive patients decreased considerably (-14.0+/-5.9%), while it increased in stable patients (+9.9+/-4.6%, p = 0.004). Heart rate rose significantly in hypotensive patients (11.5+/-3.8%) in comparison to stable patients (-0.2+/-2.8%, p = 0.02). However, no significant differences in autonomic function were observed between hypotensive and stable patients. Although both groups showed impaired autonomic function, no significant correlation between changes in haemodynamics during dialysis and autonomic function at rest could be ascertained. In conclusions, hypotension during haemodialysis is not related to a patient's autonomic function at rest. This suggests that structural neuronal differences are not responsible for the severe decrease in systemic vascular resistance in intradialytic hypotension. PMID- 9988357 TI - Factors affecting the respiratory ratio during cardiopulmonary by-pass. AB - Despite the wide use of hypothermic cardiopulmonary bypass (CPB) during open heart surgery there is little information about the patient metabolism. In particular no complete studies addressed the assessment of the respiratory ratio (RR) during CPB at different core temperatures. Therefore a clinical study was performed in order to evaluate the oxygen consumption (VO2) and carbon dioxide production (VCO2) in adult patients with valvular or coronary heart disease undergoing CPB. Twenty-five patients (16 male, 9 female) aged between 26 and 76 (54.2+/-12.4 mean +/- SD) were the subjects of this study. Measurements (102) were taken at various perfusion flow rates (from 1.6 to 2.9 L/min(-1) x m(-2)) and temperatures (from 24 to 37 degrees C). Arterial and mixed venous gas analyses were performed and O2 and CO2 concentrations were calculated, including the carbamate contribute. We calculated VO2, VCO2 and then RR from artero-venous differences in O2 and CO2 contents. Both VO2 and VCO2 showed a positive linear correlation with temperature (r = 0.82 and r = 0.59 respectively) and with blood flow rate (r = 0.61 and r = 0.29 respectively). The mean RR was 0.78+/-0.28 and more than 84% of RR values fell in the range 0.5-1.2. No significant correlation between RR and temperature and blood flow rate was observed. VCO2 and RR showed a positive linear correlation with the gas to blood flow rate ratio (r = 0.37 and r = 0.49 respectively). PMID- 9988358 TI - Haemodynamic changes in patients undergoing high-risk PTCA under protection of transfemoral heart- lung machine support with centrifugal pumps. AB - Patients with a high risk for myocardial revascularization by cardiological or surgical means can be supported during high-risk PTCA with mechanical circulatory support (supp HR-PTCA). Between November 1994 and June 1997 we performed 28 supp HR-PTCA's under protection of a heart-lung machine (HLM) with femoro - femoral cannulation under regional anesthesia. We approached 2.8+/-1.5 stenoses and 1.7+/ 0.6 vessels per patient. Primary success rate was 95 percent of the treated vessels. During unloading, pulmonary artery mean pressure fell to 42+/-29% of the starting value, and LVEDP was decreased to 36+/-42%. Mechanical unloading also resulted in a significant reduction of left ventricular volumes (unloaded LVEDVI and LVESVI represent 76.8% and 76.6% of pre-unloaded values, respectively, p<0.05). All patients except one survived the procedure and could be discharged from the hospital. Femoro-femoral cardio-pulmonary bypass under regional anesthesia provides sufficient protection for high risk PTCA procedures and enables high risk patients to benefit from coronary revascularization. PMID- 9988359 TI - Surface modification of polyurethane heart valves: effects on fatigue life and calcification. AB - Polyurethane heart valves can be functionally durable with minimal calcification, in vitro. In vivo, these characteristics will depend on the resistance of the polyurethane to thrombogenesis and biodegradation. Surface modification may improve the polyurethane in these respects, but may adversely affect calcification and durability. This study investigates the effects of surface modifications of two polyurethane heart valves (PEU and PEUE) on their in vitro fatigue and calcification behaviour. Modifications included heparin, taurine, 3 aminopropyltriethoxysilane and polyethylene oxide (PEO). Neither hydrodynamic function nor leaflet thickness distribution was significantly altered by surface modification. PEO-modification was detrimental to valve fatigue durability and calcification. Heparin, taurine or aminosilane modifications of PEU valves increased durability. Aminosilane modification of PEUE valves increased durability compared with PEO modification. Appropriate surface modification may be useful to improve blood compatibility of implantable polyurethanes, and may also be advantageous as regards fatigue durability of flexing materials in longterm applications. PMID- 9988360 TI - Blood separation with two different autotransfusion devices: effects on blood cell quality and coagulation variables. AB - The quality of blood products obtained from two different autotransfusion devices (CATS- Fresenius and Sequestra 1000 - Medtronic) was tested in 27 patients undergoing elective orthopaedic surgery. Blood products provided from our institutional blood bank (n = 16) served as controls. Hemodiluted blood was separated into platelet poor plasma (PPP), platelet rich plasma (PRP), and packed red cells (PRC) and analysed for blood cell count, fibrinogen concentration, thromboplastin time, partial thromboplastin time, platelet aggregation and platelet recovery rate. Coagulation variables showed no differences between the CATS-group (n = 14) and the Sequestra 1000-group (n = 13). The volume of PRP was lower in the Sequestra 1000-group (45+/-3 ml vs. 89+/-1 ml, p<0.05), but hematocrit was higher (14.4+/-7.8% vs. 8.5+/-2.8%, p<0.05). PPP produced with CATS contained a higher concentration of white blood cells (0.6+/-0.2 Gpt/l vs. 0.1+/-0.01 Gpt/l, p<0.05) and thrombocytes (163+/-74 Gpt/l vs. 11+/-12 Gpt/l, p<0.05). Hematocrit of PRC was significantly higher in the CATS-group (73.8+/ 2.0% vs. 69.0+/-6.5%, p<0.05). Blood products were of high quality in both groups and comparable to or superior than blood products provided from our institutional blood bank. PMID- 9988361 TI - Serotonergic function after (+/-)3,4-methylene-dioxymethamphetamine ('Ecstasy') in humans. AB - (+/-)3,4-Methylene-dioxymethamphetamine (MDMA, or 'Ecstasy') effects on serotonin system function and behaviour in humans are unclear. Fifteen MDMA users, who did not have other drug dependencies or alcohol abuse, and had not used other drugs for prolonged periods, and 15 control individuals were included in a study to assess the biological and psychological changes after chronic use of MDMA. Prolactin and cortisol responses to D-fenfluramine challenge, clinical psychobehavioural changes, personality characteristics, including mood, aggressiveness and temperamental aspects, were evaluated 3 weeks after MDMA discontinuation. MDMA users had significantly reduced prolactin and cortisol responses in comparison with control individuals (p < 0.001 and p < 0.005, respectively). Dysphoria and mood changes were exhibited in seven individuals, tiredness in five and sensation-seeking behaviour in twelve at the clinical evaluation. Significantly higher scores were found in MDMA individuals than in control individuals for Minnesota Multiphasic Personality Inventory subscale for Depression, for Buss Durkee Hostility Inventory direct and guilt subscales, for Hamilton Depression Rating Scale and for novelty-seeking Tridimensional Personality Questionnaire subscale. Prolactin responses to D-fenfluramine stimulation area under the curve among MDMA users were negatively correlated with direct aggressiveness scores for Buss Durkee Hostility Inventory; a negative correlation between prolactin responses and novelty-seeking scores was also evidenced among MDMA users. These data suggest an association between serotonin system impairment and MDMA use in humans; in interpretation of these results, the possibility that serotonin deficit in MDMA individuals was partially related to a premorbid condition, in relationship with novelty-seeking behaviour and mood disorders, can not be excluded. PMID- 9988362 TI - Compliance in depressed patients treated with fluoxetine or amitriptyline. Belgian Compliance Study Group. AB - Two dimensions of compliance (drop-outs and adherence) were investigated in patients treated with antidepressant drugs. Efficacy, compliance and its determinants were investigated in 66 patients suffering from major depressive disorder and treated in a double-blind manner with fluoxetine 20 mg/day or amitriptyline 150 mg/day for 9 weeks. Overall effectiveness [50% decrease in the initial Hamilton Rating Scale for Depression (HAM-D)] was similar in both groups (62.8% for fluoxetine, 58.1% for amitriptyline). The dropout rate due to side effects was 35.5% for amitriptyline and 5.7% for fluoxetine. A logistic regression analysis revealed that the initial HAM-D score was not predictive for dropping out, but this outcome was instead determined by sex (increased risk for males), age (increased risk for being younger) and occurrence of severe side effects. Adherence was estimated using electronic Medication Event Monitoring System and defined as the percentage of days when the correct dose was taken out of the medication container. Of the patients studied 37% had an adherence of less than 70%. There was no relationship between adherence and efficacy and adherence was similar in patients on fluoxetine or amitriptyline. Side effects were not predictive of being adherent or not, but a higher initial HAM-D score predicted a higher adherence to the medication regimen. The demographic variables had no significant effect. The present study suggests that the link between efficacy, side effects and compliance or adherence is more complex than is generally believed and that early termination and non-adherence seem to be determined by different factors. PMID- 9988363 TI - Co-administration of citalopram and clozapine: effect on plasma clozapine levels. AB - Antidepressants are frequently used in the treatment of depressive symptoms associated with schizophrenia. In patients taking clozapine, choice of antidepressant is complicated by additive pharmacodynamic effects and by pharmacokinetic interactions. We predicted that citalopram would not elevate plasma clozapine levels when the two drugs were co-administered because it does not inhibit the relevant enzyme systems. In this preliminary study of five patients given citalopram and clozapine there was no overall change in mean clozapine levels. Based on this limited evidence, citalopram might be the antidepressant of choice in patients taking clozapine. PMID- 9988364 TI - Neuroendocrine and hypothermic effects of 5-HT1A receptor stimulation with ipsapirone in healthy men: a placebo-controlled study. AB - The neuroendocrine effects of 5-hydroxytryptamine-1A (5-HT1A) receptor stimulation remain uncertain in humans, in respect to both anterior and posterior pituitary hormone release. This is important because these endocrine responses are often used as indications of 5-HT1A receptor sensitivity. The link between receptor stimulation and subsequent hormone release is more direct with posterior pituitary hormones because there is no intermediate hypothalamic peptide in the pathway. Theoretically, therefore, posterior pituitary hormones should be more valid indicators of central 5-HT1A receptor sensitivity. We used the 5-HT1A receptor partial agonist ipsapirone (20 mg) as an oral serotonergic challenge drug in a random-order, double-blind placebo-controlled study of 12 healthy men. Blood sampling occurred at 30 min intervals up to 180 min after the administration of drug or placebo. Ipsapirone caused clear and significant elevations in adrenocorticotrophin (ACTH), cortisol (CORT), prolactin (PRL), and growth hormone (GH) release. Peak hormone and ipsapirone blood levels both occurred at 60 min after ipsapirone administration. Release of the posterior pituitary hormone oxytocin was also stimulated, but less robustly and with more baseline variation. Temperature fell significantly more after ipsapirone than placebo. These results contrast with previous studies, which found no effect of ipsapirone on PRL and GH release in humans, but are in accordance with data using other 5-HT1A agonist drugs. The presence of an oxytocin response to ipsapirone suggests that oxytocin is a potential marker for serotonergic function in neuroendocrine challenge studies, but this awaits further study. PMID- 9988365 TI - Successful challenge with clozapine in a history of eosinophilia. AB - Eosinophilia has been encountered from 0.2 to 61.7% in clozapine-treated patients, mostly with a transient course and spontaneous remission. There have been few reports, however, which have investigated a challenge with clozapine in patients previously showing eosinophilia. Two case reports are presented: the first with clozapine challenge after eosinophilia, the second under clozapine treatment and no previous haematological side effects. The challenge case showed eosinophilia with 1.2 10(9)/l (z = 1.79, p = 0.04) being followed by normalization despite clozapine continuation, whereas the maximum value reached 2.1 10(9)/l in the single episode case, with consecutive normalization and uninterrupted treatment. Eosinophilia caused by clozapine was observed in challenge, preceded by a faster neutrophil production and consecutive decrease (z = 2.27, p = 0.01). A challenge with clozapine was feasible and showed no clinical symptoms of eosinophilia. PMID- 9988366 TI - Mirtazapine in recurrent brief depression. AB - Recurrent brief depression (RBD) has a high prevalence in the general population (approximately 10%). At present, data on the treatment of RBD are sparse. Results of treatment studies with selective serotonin reuptake inhibitors (fluoxetine, paroxetine) did not demonstrate superiority of the active drug over placebo in RBD. We report about two patients with RBD treated with mirtazapine over a period of 4 months. Mirtazapine is a noradrenergic with specific selective serotoninergic antidepressant. Patients had to keep a diary in order to document psychopathological symptoms of major depression according to DSM-IV. We showed a marked reduction of severity, duration and frequency of brief depressive episodes in two patients with RBD treated with 30 mg mirtazapine over a period of 4 months. Mirtazapine enhances serotonergic as well as noradrenergic neurotransmission. This dual mechanism of action may be necessary to improve RBD. Consequently, mirtazapine might be a treatment option for patients with RBD. However, our preliminary observations need to be substantiated in controlled studies. PMID- 9988368 TI - Enzyme-based assay for quantification of paraoxon in blood of parathion poisoned patients. AB - 1. Paraoxon concentration was estimated by means of inhibition kinetics observed with electric eel acetylcholinesterase (AChE) which was determined by a modified Ellman procedure. In human plasma, paraoxon was stabilized by inactivation of paraoxonase with EDTA and aluminon and by inhibition of butyrylcholinesterase with ethopropazine. Paraoxon (1-50 ng) was recovered at 86+/-1.7% (mean+/-s.e.m.) in ether extracts from 0.5 ml samples of spiked stabilized plasma. It could be stored without loss at - 20 degrees C for at least 1 month. 2. The enzyme-based assay was applied to follow the paraoxon plasma concentrations in three suicidal patients with severe parathion poisoning. In poisoning with excessive doses and initial paraoxon concentrations above 500 nM, therapeutic obidoxime concentrations of approximately 10 microM failed to essentially reactivate erythrocyte AChE in vivo, while reactivatability ex vivo was nearly complete. With the plasma concentrations of paraoxon dropping below 100 nM, however, reactivation by obidoxime became significant. Unexpectedly, paraoxon levels occasionally reincreased during treatment and resulted in re-inhibition of AChE, bearing some resemblance to the Intermediate Syndrome. 3. The paraoxon concentrations measured fitted satisfactorily the values calculated from the kinetic constants previously obtained for AChE inhibition and obidoxime-induced reactivation in vitro. This indicates that diethylphosphoryloxime formation during obidoxime-induced reactivation does not markedly contribute to the re inhibition of AChE as observed in vitro. PMID- 9988369 TI - Protection by extracellular glutathione against sulfur mustard induced toxicity in vitro. AB - 1. The present study characterizes the role of extracellularly added glutathione in protection against sulfur mustard (HD) toxicity in a macrophage monocyte cell line J774. 2. Toxic effects of HD depend on dose and duration of exposure with an ED50 of 50 and 75 microM for dividing and confluent cells respectively. 3. Exposure to HD, 100-200 microM caused approximately 15% decrease in the cellular glutathione (GSH) content 2 h after exposure, pretreatment with GSH, 0.2-10 mM, elevated cellular GSH approximately x 1.5. 4. GSH pretreatment increased cell viability after HD 2-3-fold. Similar protective effects of GSH treatment were found in a human epidermoid carcinoma cell line (KB). 5. Protection by post treatment with GSH was apparent even 60 min post HD exposure. 6. No protection was afforded when the intracellular GSH concentration was elevated prior to exposure and the extracellular GSH had been washed out. However, GSH depleted cells were more sensitive to HD than normal cells, and were also protected by addition of GSH to the growth medium, although the intracellular GSH content remained low. 7. We conclude that it is essential for the GSH to be present extracellularly in order to protect cells from HD toxicity. 8. Our findings have therapeutic implications in particular for the protection of lungs after inhalation exposure to HD vapor. PMID- 9988370 TI - Inhibition of protein synthesis by zinc: comparison between protein synthesis and RNA synthesis. AB - Inhalation of zinc fumes may lead to the acute respiratory distress syndrome. The mechanisms of pulmonary zinc toxicity are not yet understood. Therefore we investigated zinc-dependent depression of protein and RNA synthesis in rat and human lung cell lines. 1. After exposure to 120 or 150 micromol/l zinc, RNA synthesis as assessed by uridine incorporation decreased by 60-70% between 0 and 2 h exposition in rat alveolar type II cells (L2 cells) and human fibroblast-like cells (11Lu and 16Lu cells), and by 90% between 0 and 4 h in carcinoma-derived cells (A549 cells). 2. After 2 h exposure, L2, 11Lu, and 16Lu cells were half maximally inhibited by 50 micromol/l zinc, whereas A549 cells were more resistant with half-maximal inhibition at 100 micromol/zinc. 3. Protein and RNA synthesis was inhibited in parallel in L2, 11Lu, and A549 cells as indicated by simultaneous determination of uridine and amino acid incorporation. In 16Lu cells, the decline in protein synthesis preceded RNA synthesis inhibition. Pretreatment with RNA synthesis inhibitors (amanitin or actinomycin D) had no effect on time curve and intensity of RNA synthesis inhibition. Taken together, our results indicate that the suppression of RNA and protein synthesis likely are independent phenomena, due to direct zinc effects on these biosynthetic pathways. PMID- 9988371 TI - Microsomal metabolism of carbamazepine and oxcarbazepine in liver and placenta. AB - Metabolism of both carbamazepine (CBZ) and oxcarbazepine (OCBZ) were catalyzed by human liver microsomes and microsomes from livers of CBZ-induced or non-induced C57BL/6 mice. Human placental microsomes metabolized only OCBZ. Mouse liver microsomes metabolized CBZ to carbamazepine-10,11-epoxide (CBZ-E), 10-hydroxy 10,11-dihydro-carbamazepine (10-OH-CBZ), 3hydroxy-carbamazepine (3-OH-CBZ), 10,11 trans-dihydroxy-10,11-dihydro-carbamazepine (10,11-D) and to an unidentified metabolite. CBZ-pretreatment of mice increased both ethoxyresorufin O-deethylase activity in the liver and the amount of CBZ-E in microsomal incubations regardless of the age of mice. Human liver microsomes catalyzed the formation of CBZ to 9-hydroxymethyl-10-carbamoyl acridan (9-AC) in addition to CBZ-E, 3-OH-CBZ and 10-OH-CBZ. OCBZ was metabolized to its active metabolite in all incubations. An unknown metabolite was also present in some of the incubations. Human liver microsomes catalyzed only minute covalent binding of CBZ and OCBZ to DNA. Binding of OCBZ was, however, one order of magnitude greater than binding of CBZ. Human placental microsomes from the mothers on CBZ therapy did not catalyze CBZ metabolism. The same microsomes catalyzed OCBZ metabolism to 10-OH-CBZ and to an unknown metabolite. These results indicate autoinduction in CBZ metabolism in mouse liver. Due to the higher binding of OCBZ than CBZ to DNA in vitro, further studies on the potential mutagenicity of OCBZ may be warranted. PMID- 9988372 TI - The pre-clinical assessment of QT interval prolongation: a comparison of in vitro and in vivo methods. AB - The literature was searched for in vivo dog studies reporting QT prolongation and in vitro studies reporting increased myocardial action potential duration, which indicates the potential to prolong QT interval, for nine non-cardiac drugs that have been reported to produce QT prolongation in man. The drugs were: astemizole; terfenadine; erythromycin; sparfloxacin; cisapride; probucol; terodiline; risperidone and sertindole. 1. There were reports of the appropriate finding with in vitro methods for six of the drugs and with in vivo methods for seven of the drugs. No reports were found concerning the remaining drugs with each method. This indicates that both methods are effective and each method would have correctly identified the drugs in question as having the potential to prolong the QT interval in man in all cases for which studies were reported. 2. This suggests that, if properly conducted, either method alone is sufficient for the pre clinical assessment of QT interval prolongation. This does not support the routine use of both methods before the administration of new drugs to man. PMID- 9988373 TI - Mechanistic modeling of rodent liver tumor promotion at low levels of exposure: an example related to dose-response relationships for 2,3,7,8-tetrachlorodibenzo p-dioxin. PMID- 9988374 TI - Mechanistic model predicts a U-shaped relation of radon exposure to lung cancer risk reflected in combined occupational and US residential data. AB - A mechanistically based cytodynamic two-stage (CD2) cancer model was shown recently to predict both ecologic US county data and underground-miner data on lung-cancer mortality (LCM) vs radon concentration, indicating biological plausibility of the apparent negative dose-response relation exhibited by the ecologic data. To further investigate this hypothesis, the CD2 model was fitted to combine age-specific LCM data vs estimated radon-exposure in white females of age 40+ years in 2821 US counties during 1950-1954 using new estimates of county specific mean residential radon exposure, and in five cohorts of underground nonsmoking miners. The negative association of radon levels and corresponding county-level LCM rates apparent in women dying in 1950-1954 (11% of whom never smoked) was also apparent in women of age 60+ years (5% of whom never smoked). The CD2 fit obtained to the combined residential and occupational data was found to predict the combined data using biologically plausible parameter values, and also to predict inverse dose-rate effects exhibited in nonsmoking miner data to which the CD2 model was not fit. These results are consistent with the hypothesis that residential radon exposure has a nonlinear U-shaped relation to LCM risk, and that current linear extrapolation models substantially overestimate such risk. PMID- 9988375 TI - A cancer risk model with adaptive repair. AB - The cancer risk model described herein first appeared in 1982. The model provides a plausible mechanism with biological underpinnings that might reasonably explain observed phenomena in cancer dose-response studies that are not being addressed by the risk models currently in use. This article is a summary and explanation of the features of the model that relate to hormesis. Data from several saccharin studies served in large part to motivate the original research, and were used to illustrate beneficial low-dose effects that could be explained by the model. The model itself is a function of linear ratios of the administered dose x. Linear ratios arise naturally from non-linear Michaelis-Menten kinetics, as described in the next section. The one-hit cancer risk model is used to illustrate the hormetic concepts brought out by linear ratios. The one-hit model is modified to account for repair and for non-linear kinetics, by using a linear ratio of the administered dose instead of the actual administered dose, and by expressing the probability that a 'hit' is repaired as a linear ratio of the administered dose. The phenomenon of hormesis - or low-dose beneficial effects-has been widely observed and accepted. Yet none of the cancer risk models currently in wide use have attempted to accommodate hormetic effects. The modified one-hit model developed herein does not attempt to account for elimination or detoxification, but nevertheless it provides plausible explanations for certain classes of observed hormetic phenomena associated with experimental testing of carcinogenic substances in animals. PMID- 9988376 TI - U-shaped dose-response curves for carcinogens. PMID- 9988377 TI - Genealogy reconstruction from short tandem repeat genotypes in an Amazonian population. AB - We have reconstructed partial genealogies in a sample of 44 SW Amazonian Rondonian Surui, in which 45 dinucleotide short tandem repeat polymorphisms had previously been typed. The genotypes of 488 pairs of individuals having an age difference of 13 or greater were compared, and parentage was excluded if a pair failed to share an allele at more than one locus. In order to test the power of this method, we computed the expected distribution of the number of exclusionary loci for such pairs of unrelated individuals, as well as that for individuals with different degrees of relatedness, and compared it to the observed distribution. We estimated that the pairs compared contained approximately 20% of individual pairs with a first-cousin relation or closer. A total of 25 pairs were identified as possible parent-child. In three instances, we could identify two or more children having a common parent; we computed a relatedness coefficient in order to establish whether the children were full or half sibs. The genealogies inferred show that instances of polygyny and polyandry (or, alternatively, serial mating), in addition to apparent monogamy, can be found among the Surui. The Surui sample can be used as a model for paleoanthropological populations, in which the determination of relatedness can provide further insights into the social structure of past populations. We estimate that, depending on the history of the populations and the degree of inbreeding, 10-20 highly informative nuclear loci should be typed in order to infer genealogies with acceptable confidence. PMID- 9988378 TI - Population substructure and isolation by distance in three continental regions. AB - Isolation by distance and divergence from a shared population history are two sources of population substructure. Isolation by distance erases population history as populations approach migration-drift equilibrium, while diverging populations descended from a single ancestral population will accumulate genetic differences with time. Here I investigate how much of the worldwide genetic diversity from Jorde et al.'s ([1997] Proc. Natl. Acad. Sci. USA 94:3100-3103) 60 tetranucleotide short tandem repeat (STR) data can be explained by isolation by distance. I use Slatkin's measure of population substructure, R(ST), principal components analyses, and Mantel tests to investigate the pattern of genetic diversity at both the intercontinental and intracontinental levels. Geographic distance accounts for almost 60% of world-wide interpopulation genetic relationships. Within continents, the correlations are less, although not significantly so because of wide confidence intervals. These results suggest that populations have not reached migration-drift equilibrium and that there is information in STR data to reconstruct population history. The level of population substructure worldwide is consistent with previous observations, but at the intracontinental level substructure is less. When one examines diversity against distance from the centroid, one sees excess heterozygosity in Africa, a pattern also noted by Stoneking et al. ([1998] Genome Research 7:1061-1071). A larger effective population size in Africa could explain the excess diversity. Greater gene flow in Africa is an unlikely explanation because the African R(ST) value is slightly larger than the Asian and European R(ST)s, pointing to less gene flow and greater substructure among African populations. Furthermore, there are differences in patterns between heterozygosity and allele size variance. Heterozygosity has a higher correlation with distance from the centroid than does allele size variance, and this may reflect demographic history. Kimmel et al. ([1998] Genetics 148:1921-1930) have shown that after a population expansion heterozygosity returns to equilibrium more quickly than does allele size variance. The contrasting patterns between heterozygosity and allele size variance may reflect different times after an expansion. However, simulations and further work need to be done to more thoroughly investigate the possibility that these data reflect population expansions. PMID- 9988379 TI - Body size and physique among Canadians of First Nation and European ancestry. AB - The purpose of this study was to compare body size and physique among Canadians of Aboriginal (First Nation [FN]) and European ancestry (EA) from the northern Ontario communities of Temagami and Bear Island. The sample consisted of 130 FN and 494 EA participants including adults (20-75 years: 214 men, 234 women) and youth (5-19 years: 97 boys, 79 girls). Indicators of body size and physique included stature, the sitting height-to-stature ratio (SSR), body mass, BMI, estimated upper-arm muscle area, biacromial, bicristal, biepicondylar, and bicondylar breadths, and the Heath-Carter anthropometric somatotype (endomorphy, mesomorphy, and ectomorphy). There were few differences in body size between FN and EA, with the exception of adult females. Adult FN females were significantly heavier and had greater bone breadths than EA women (P < 0.001). On the other hand, somatotype differed significantly between EA and FN by age and sex, except for 5-19-year-old females. Among boys and men, FN had greater endomorphy (P < 0.03), whereas FN men also had lower ectomorphy (P < 0.01). Among women, FN were significantly more endomorphic and mesomorphic and less ectomorphic (P < 0.001). Although results for 5-19-year-old females were not significant, they were in the same direction as the other groups (greater endomorphy). Forward stepwise discriminant function analyses indicated that endomorphy was the most important discriminator between FN and EA by age and sex. PMID- 9988380 TI - Biological affinities and adaptations of Bronze Age Bactrians: IV. A craniometric investigation of Bactrian origins. AB - Discovery of a previously unknown Bronze Age civilization (Oxus civilization) centered on the oases of Central Asia revealed the presence of large, preplanned urban centers immediately above sterile soil. Given the absence of local antecedents, the sudden appearance and proliferation of these Oxus civilization urban centers in the oases of Bactria and Margiana immediately raised the issue of where the inhabitants of these urban centers came from. Three hypotheses have been offered by archaeologists to account for the origins of Oxus civilization populations. These include the early influence model, the late colonization model, and the trichotomy model. Eleven craniometric variables from 12 Aeneolithic and Bronze Age samples, encompassing 657 adults from Central Asia, Iran, and the Indus Valley, are compared to test which if any of these hypotheses are supported by the pattern of phenetic affinities possessed by the Oxus civilization inhabitants of the north Bactrian oasis. Craniometric differences between samples are compared with Mahalanobis generalized distance (d2), and patterns of phenetic affinity are assessed with two types of cluster analysis (WPGMA, neighbor-joining method), multidimensional scaling, and principal coordinates analysis. Results of this analysis provide no support for either the late colonization model or the trichotomy model but do offer some support for the early influence model. Nevertheless, it is clear that the early influence model fails to account for a shift in interregional contacts, perhaps from western China to the north around 2000 BC, that appears to have played a major role in the origins of the Oxus civilization inhabitants of the north Bactrian oasis. PMID- 9988381 TI - Collateral relatives of American Indians among the Bronze Age populations of Siberia? AB - Nonmetric and metric traits were studied in cranial series representing prehistoric and modern populations of America and Siberia. Frequencies of the infraorbital pattern type II (longitudinal infraorbital suture overlaid by the zygomatic bone) are universally lower in Amerindians than in Siberians. The os japonicum posterior trace, too, is much less frequent in America than in Siberia. The only two Siberian groups with an almost Amerindian combination are late third to early second millennium BC populations from Okunev and Sopka, southern Siberia. The multivariate analysis of five nonmetric facial traits and ten facial measurements in 15 cranial series reveals two independent tendencies. One of them shows a contrast between prehistoric Siberian Caucasoids and modern Siberian Mongoloids; the second one sets Amerindians apart from others. Prehistoric people who lived west of Lake Baikal and modern Uralic speakers are intermediate between Siberian Caucasoids and Siberian Mongoloids; Eskimos, Aleuts, and Chukchi are intermediate between Siberian Mongoloids and Amerindians; and Okunev and Sopka are intermediate between Siberian Caucasoids and Amerindians. Our results suggest that people of Okunev and Sopka are collateral relatives of Amerindians with some Caucasoid admixture. PMID- 9988382 TI - Kinematic data on primate head and neck posture: implications for the evolution of basicranial flexion and an evaluation of registration planes used in paleoanthropology. AB - Kinematic data on primate head and neck posture were collected by filming 29 primate species during locomotion. These were used to test whether head and neck posture are significant influences on basicranial flexion and whether the Frankfurt plane can legitimately be employed in paleoanthropological studies. Three kinematic measurements were recorded as angles relative to the gravity vector, the inclination of the orbital plane, the inclination of the neck, and the inclination of the Frankfurt plane. A fourth kinematic measurement was calculated as the angle between the neck and the orbital plane (the head-neck angle [HNA]). The functional relationships of basicranial flexion were examined by calculating the correlations and partial correlations between HNA and craniometric measurements representing basicranial flexion, orbital kyphosis, and relative brain size (Ross and Ravosa [1993] Am. J. Phys. Anthropol. 91:305-324). Significant partial correlations were observed between relative brain size and basicranial flexion and between HNA and orbital kyphosis. This indicates that brain size, rather than head and neck posture, is the primary influence on flexion, while the degree of orbital kyphosis may act to reorient the visual field in response to variation in head and neck posture. Regarding registration planes, the Frankfurt plane was found to be horizontal in humans but inclined in all nonhuman primates. In contrast, nearly all primates (including humans) oriented their orbits such that they faced anteriorly and slightly inferiorly. These results suggest that for certain functional craniometric studies, the orbital plane may be a more suitable registration plane than Frankfurt "Horizontal." PMID- 9988383 TI - Cranial growth in Homo erectus: how credible are the Ngandong juveniles? AB - Confusion exists regarding the developmental ages of numerous Asian and southeast Asian Homo erectus fossils because of Weidenreich's contention that Pithecanthropus fused its sutures prematurely relative to H. sapiens. I reevaluate the cranial developmental ages of the Ngandong "juveniles" (2, 5, 8, 9) based on a series of indicators of youth (superstructure development, suture development/fusion, and cranial thickness) and cranial contours. The Ngandong juveniles are compared with H. sapiens adults (n = 281) and subadults (n = 81) and with Ngandong and other H. erectus adults (n = 20) and subadults (n = 4). Cranial contours are assessed using bivariate plots of arc vs. chord measurements. All indicators suggest that Ngandong 5 and 9 are adults, whereas Ngandong 8 is an older juvenile or young adult and Ngandong 2 is a juvenile with a developmental age range of greater than 6 and less than 11 years. In addition, adult cranial contours and the pattern of contour development are similar between Ngandong adults and other H. erectus adults. There is nothing in the cranial contour data to suggest that Ngandong is, despite a relatively large brain, transitional in vault shape between H. erectus and H. sapiens. PMID- 9988384 TI - A new correction procedure for calibrating dental caries frequency. AB - The incisors and canines and the premolars and molars show differential resistance to cariogenic factors. The anterior teeth have a lower caries frequency than the posterior teeth. However, these tooth classes are lost differentially in postmortem stages due to their anatomical structures. This differential postmortem tooth loss distorts proportions between the anterior and posterior tooth classes. The disproportionality can affect the calculation of total caries prevalence. In this paper, we propose a new calibration procedure which removes this disproportionality and call it the proportional correction factor. For this procedure, the caries rates of anterior and posterior teeth are corrected by multiplying the anterior teeth by three-eighths and the posterior teeth by five-eighths. These fractions are derived from the human dental formula which contains three anterior and five posterior teeth by side. The correction factor is more effective if the proportion of anterior to the posterior teeth is extremely distorted. When this procedure is used with the caries correction factor, it provides a useful way to approach to an almost true caries prevalence. PMID- 9988385 TI - Association between cytosolic low molecular weight phosphotyrosine-phosphatase and malaria--a possible mechanism. AB - Cytosolic low molecular weight phosphotyrosine-phosphatase shows dephosphorylating activity of the band 3 protein. Increased phosphorylation of this protein increases membrane rigidity and resistance to invasion of red blood cells by malarial parasites. This observation may explain the negative association previously reported by our group between the high activity *C allele of cytosolic low molecular weight phosphotyrosine-phosphatase and past malarial morbidity. PMID- 9988386 TI - Mutations in human gonadotropin genes and their physiologic significance in puberty and reproduction. AB - OBJECTIVE: Human gene mutations provide an opportunity to study the pathophysiology of the disease process as well as normal physiology. The purpose of the present report was to review known human gene mutations that affect gonadotropin secretion. DESIGN: A retrospective analysis of studies of human gene mutations that affect hypothalamic, pituitary, and gonadal function was conducted. RESULT(S): Mutations have been identified for at least three genes that cause inherited hypogonadotropic hypogonadism. In addition, gene mutations for the beta-subunits of FSH and LH have been characterized. Both activating and inactivating mutations have been identified for the gonadotropin receptor genes. CONCLUSION(S): The identification of human gene mutations has furthered our understanding of the normal processes of pubertal development and fertility. PMID- 9988387 TI - Reconstituting eggs: the ethics of cytoplasm donation. PMID- 9988388 TI - Clinical value of using an automated sperm morphology analyzer (IVOS). AB - OBJECTIVE: To determine the clinical value of automated normal sperm morphology outcomes. DESIGN: Prospective clinical study. SETTING: Clinical and research assisted reproduction laboratory. PATIENT(S): Two hundred seven GIFT cycles. INTERVENTION(S): The wife was induced to superovulate, laparoscopically aspirated, and the gametes were transferred laparoscopically. The husband's sperm morphology was evaluated with use of a sperm morphology analyzer using the strict criteria classification system. MAIN OUTCOME MEASURE(S): Normal sperm morphology, IVF, and pregnancy outcomes. RESULT(S): The logistic regression model showed that normal sperm morphology was significantly associated with fertilization in vitro, as dependent (age) and independent variables. Analyzing the fertilization rates across the 5% normal sperm morphology cutoff point, a fertilization rate of 39.39% (< or = 5%) compared with 62.92% (>5%) was obtained. The logistic regression model showed that normal sperm morphology was also a significant predictor of pregnancy when allowing for the number of oocytes transferred and female age. Analyzing the pregnancy rates across the 5% normal sperm morphology cutoff point, pregnancy rates of 15.15% (< or = 5%) and 37.36% (>5%) were obtained. CONCLUSION(S): Normal sperm morphology as evaluated by the automated semen analyzer (IVOS) was shown to adhere to the same fertility cutoff point (5%), as determined by the manual evaluation of sperm morphology. Automated normal sperm morphology outcomes also were found to be significant predictors of IVF and pregnancy in a GIFT program. PMID- 9988389 TI - Differences in the attitudes of couples whose children were conceived through artificial insemination by donor in 1980 and in 1996. AB - OBJECTIVE: To compare the attitudes of couples whose children were conceived through artificial insemination by donor (AID) in 1980 and in 1996. DESIGN: Replication study. SETTING: Infertility clinic of the Utrecht university hospital. PATIENT(S): Couples who conceived a child through AID in 1980 (n = 134) or in 1996 (n = 110). INTERVENTION(S): Anonymous questionnaires. MAIN OUTCOME MEASURE(S): Answers to questionnaires. RESULT(S): Couples who conceive a child through AID still strongly prefer (84%) absolute anonymity of the donor. In both 1980 and 1996, most couples (approximately 80%) decided not to inform their child about the nature of his or her conception. In 1996, couples who considered informing their child hesitated significantly less and showed significantly more openness toward others. In addition, more couples wanted unidentifiable data about the donor and considered it more important to use the same donor for a subsequent child. CONCLUSION(S): Between 1980 and 1996, the number of couples who conceived a child through AID and adhered to absolute anonymity of the donor and secrecy toward the child remained the same, whereas their openness toward others and desire for unidentifiable data about the donor increased. PMID- 9988390 TI - Effects of human oviductal cell coculture on various functional parameters of human spermatozoa. AB - OBJECTIVE: To investigate the effect of human oviductal cells on various sperm functions in vitro. DESIGN: Controlled experimental laboratory study. SETTING: University gynecology unit. PATIENT(S): Women undergoing tubal ligation or hysterectomy and men who were visiting our subfertility clinics. INTERVENTION(S): Coculture of oviductal cells with human spermatozoa in vitro; sperm functions were determined after coculture. MAIN OUTCOME MEASURE(S): Capacitation, acrosome reaction, zona binding, and oocyte fusion. RESULT(S): Oviductal cells and conditioned medium induced more spermatozoa to capacitate than did control medium. Although there was no difference in the spontaneous acrosome reaction between any of the groups, the coculture group had a lower percentage of acrosome reacted spermatozoa after calcium ionophore challenge than did the control and conditioned medium groups. Coculture and conditioned medium treatment reduced the number of spermatozoa bound to the zona pellucida. The penetration rate and penetration index of the control spermatozoa in the zona-free hamster oocyte penetration test were significantly higher than that of the cocultured or conditioned medium-treated spermatozoa. CONCLUSION(S): Human oviductal cells promoted capacitation, stabilized the acrosome, and suppressed binding to the zona pellucida and fusion with the oocyte in vitro. PMID- 9988391 TI - Enhancement or initiation of testicular sperm motility by in vitro culture of testicular tissue. AB - OBJECTIVE: To describe different techniques of testicular tissue culture and their effect on sperm motility, mainly in cases of totally immotile spermatozoa, and to compare the effect of in vitro culture with that of motility stimulants. DESIGN: Prospective study. SETTING: University teaching hospital. PATIENT(S): Ten patients undergoing testicular biopsy for diagnostic purposes or for intracytoplasmic sperm injection. INTERVENTION(S): Dissected testicular biopsy samples and tissue blocks were cultured at 37 degrees C for up to 96 hours. Immediately after dissection, immotile testicular spermatozoa were incubated for 30 minutes in pentoxifylline and 2-deoxyadenosine. MAIN OUTCOME MEASURE(S): Sperm motility and vitality. RESULT(S): Overall, dissected samples showed improved sperm motility, which peaked within 48 hours of culture. Unlike motility, vitality declined linearly, from 56.3%+/-19% at initial assessment to 18.8%+/-11% at 96 hours. Five samples had initially immotile spermatozoa, of which four acquired motility at 48 hours. In vitro culture showed results comparable with those of incubation with pentoxifylline and 2-deoxyadenosine. Culture of tissue blocks did not improve motility or vitality compared with dissected tissue. CONCLUSION(S): The motility of testicular spermatozoa was enhanced or initiated after in vitro culture. Testicular biopsy culture may be an alternative to the use of motility stimulants to obtain motile spermatozoa for intracytoplasmic sperm injection, particularly when oocytes are not immediately available. PMID- 9988392 TI - Induction of puberty with human chorionic gonadotropin and follicle-stimulating hormone in adolescent males with hypogonadotropic hypogonadism. AB - OBJECTIVE: To evaluate the clinical and hormonal responses of adolescent males with hypogonadotropic hypogonadism (HH) in response to gonadotropin replacement with the use of long-term combined hCG and FSH therapy. DESIGN: Prospective clinical study. SETTING: Clinical pediatric department providing tertiary care. PATIENT(S): Seven prepubertal males with isolated HH with a mean (+/-SD) age of 15.44+/-1.97 years and seven prepubertal males with panhypopituitarism-associated HH with a mean (+/-SD) age of 18.1+/-3.24 years were studied. INTERVENTION(S): Human chorionic gonadotropin (1,000-1,500 IU IM) and FSH (75-100 IU SC) were administered every alternate day of the week until the total induction of puberty and spermatogenesis was achieved. MAIN OUTCOME MEASURE(S): Serum testosterone levels, testicular volume, penis length, and sperm count were evaluated after the administration of hCG and FSH. RESULT(S): All patients achieved normal sexual maturation and normal or nearly normal adult male levels of testosterone. The increase in testicular size was significant in both groups. Positive sperm production was assessed in four of five patients with isolated HH and in three of three patients with panhypopituitarism-associated HH. CONCLUSION(S): Long-term combined hCG and FSH therapy is effective in inducing puberty, increasing testicular volume, and stimulating spermatogenesis in adolescent males with isolated HH and panhypopituitarism-associated HH. PMID- 9988393 TI - Effect of seminal oxidative stress on fertility after vasectomy reversal. AB - OBJECTIVE: To evaluate seminal oxidative stress in men after vasectomy reversal and to determine whether seminal oxidative stress could predict fertility after vasectomy reversal. DESIGN: Measurement of seminal reactive oxygen species (ROS) and total antioxidant capacity (TAC) in normal donors, men who were fertile after vasectomy reversal, and men who were infertile after vasectomy reversal. SETTING: A male infertility clinic of a tertiary care center. PATIENT(S): Thirty men who underwent vasectomy reversal and 17 normal donors. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Semen characteristics, seminal ROS, and TAC were measured with chemiluminescence assays in samples from donors and reversal patients. RESULT(S): Mean adjusted seminal ROS (log [ROS+1]) was higher in infertile reversal patients (2.38+/-0.25) than in normal donors (1.30+/-0.14). Seminal ROS was also higher in all (fertile and infertile reversal combined) reversal patients than in donors. Total antioxidant capacity did not differ between groups. The ROS-TAC score, a composite index of seminal oxidative stress, was a significant predictor of fertility. A ROS-TAC score of 45 or greater had a positive predictive value of 73% in predicting fertility. CONCLUSION(S): Seminal oxidative stress is associated with vasectomy reversal. The ROS-TAC score is a possible predictor of infertility after vasectomy reversal. PMID- 9988394 TI - Fertilization antigen-1 removes antisperm autoantibodies from spermatozoa of infertile men and results in increased rates of acrosome reaction. AB - OBJECTIVE: To determine if fertilization antigen (FA)-1 will remove autoantibodies from the surface of sperm cells of immunoinfertile men by immune adsorption and permit an increased acrosome reaction (AR). DESIGN: Prospective analytic study. SETTING: University medical center. PATIENT(S): Men from 18 infertile couples with autoantibodies present on their spermatozoa. INTERVENTION(S): Sperm samples after processing were examined for antibody binding and AR before and after adsorption with control medium or FA-1. MAIN OUTCOME MEASURE(S): Sperm-bound antibody was assessed by the immunobead assay (immunoglobulin [Ig] A and IgG) and the AR by induction with ionophore A23187. RESULT(S): Adsorption with FA-1 compared with control medium increased immunobead free swimming sperm an average of 50% and 76% for IgA and IgG antisperm antibodies, respectively, with 78% and 100% of the 18 semen specimens increasing significantly. The AR rate increased an average of 10.3% compared with control medium and showed improvement in 78% of the sperm samples after FA-1 adsorption. CONCLUSION(S): The FA-1 sperm antigen appears to significantly free sperm cells coated with autoantibodies in the semen of most infertile men examined. Reducing sperm-bound antibodies that inhibited the AR allowed the sperm cells to undergo successful AR induction by calcium ionophore. PMID- 9988395 TI - Effect of menopause and different combined estradiol-progestin regimens on basal and growth hormone-releasing hormone-stimulated serum growth hormone, insulin like growth factor-1, insulin-like growth factor binding protein (IGFBP)-1, and IGFBP-3 levels. AB - OBJECTIVE: To determine the effects of menopause and three different formulations of E2 plus medroxyprogesterone acetate on serum concentrations of basal and growth hormone-releasing hormone (GHRH)-stimulated growth hormone (GH), insulin like growth factor-1 (IGF-1), insulin-like growth factor binding protein (IGFBP) 1, IGFBP-3, insulin, and C peptide. DESIGN: Prospective, controlled trial. SETTING: Menopausal outpatient clinic at an academic tertiary care hospital. PATIENT(S): Nineteen postmenopausal women with different menopausal ages. Seventeen premenopausal women were included as controls. INTERVENTION(S): Oral estrogen (E2 valerate, 2 mg/d) or transdermal estrogen (50-microg or 100-microg E2 patch) was administered for 8 weeks. Medroxyprogesterone acetate (5 mg/d) was administered during weeks 3, 4, 7, and 8 of each protocol. Blood samples were collected before treatment and after the completion of each protocol from postmenopausal women, and on cycle days 6-8 from premenopausal women. MAIN OUTCOME MEASURE(S): Levels of GH, IGF-1, IGFBP-1, IGFBP-3, insulin, and C peptide. RESULT(S): Basal GH levels were negatively correlated with age in premenopausal women but not in postmenopausal women. The area under the GHRH induced GH curve decreased in older postmenopausal women after the oral estrogen protocol. Levels of IGF-1 diminished after the oral E2 protocol in postmenopausal women. CONCLUSION(S): The administration of oral, but not transdermal, E2 plus medroxyprogesterone acetate at the usual clinical doses used in postmenopausal women decreased IGF-1 levels and the response of GH to GHRH in older women. No substantial changes were detected in IGFBP-1, IGFBP-3, insulin, or C peptide levels. PMID- 9988396 TI - Changes in sex hormones during an oral glucose tolerance test in healthy premenopausal women. AB - OBJECTIVE: To assess the effect of an acute elevation in circulating insulin on serum androgen levels in healthy obese women with different body-fat distributions. DESIGN: Controlled clinical study. SETTING: The Endocrinology Unit of an academic medical center. PATIENT(S): Seventy healthy premenopausal women participated: 27 women with upper-body obesity, 22 women with lower-body obesity, and 21 normal-weight women as controls. INTERVENTION(S): A 75-g oral glucose tolerance test (OGTT) was performed for all participants. MAIN OUTCOME MEASURE(S): Anthropometry and serum concentrations of glucose, insulin, free T, DHEAS, androstenedione, E2, and sex hormone-binding globulin (SHBG) at fasting, 60 minutes, and 120 minutes after oral glucose loading. RESULT(S): Although androgens and E2 levels in all three groups declined modestly, there were no statistically significant differences in response of the sex hormones to an OGTT in the two obese groups and normal-weight women. No correlation was found between changes in sex-hormone levels during an OGTT and insulin rise. Increased body mass index and more pronounced abdominal fat localization resulted in basal hyperinsulinemia, markedly exaggerated glucose-induced insulin levels, and hyperandrogenism, as was evident by significantly elevated free T and low SHBG serum levels. CONCLUSION(S): There were no statistically significant differences in androgen response to acute hyperinsulinemia during an OGTT between obese women with different regional fat distributions and lean controls. PMID- 9988397 TI - Effect of a baseline ovarian cyst on the outcome of in vitro fertilization-embryo transfer. AB - OBJECTIVE: To determine the significance of prestimulation ovarian cysts on the response to controlled ovarian hyperstimulation and the outcome of IVF. DESIGN: Retrospective study. SETTING: In vitro fertilization unit in an academic center. PATIENT(S): One hundred thirty-seven patients undergoing IVF. INTERVENTION(S): The outcome of 71 patients who had an ovarian cyst of >10 mm detected at ultrasound examination performed on day 3 was compared with that of 66 patients who underwent a similar protocol and did not have an ovarian cyst. MAIN OUTCOME MEASURE(S): Parameters evaluated were the E2 level on the day of hCG administration, the number of follicles, the number of oocytes retrieved, the number of embryos transferred, and the pregnancy rate. RESULT(S): The E2 level on the day of hCG administration and the number of mature oocytes retrieved were lower in the group with a baseline cyst. The pregnancy rate also was significantly lower in the group with a cyst (24% versus 41%). The presence of a baseline ovarian cyst decreases the odds of pregnancy 0.37-fold (95% confidence interval, 0.16-0.87). CONCLUSION(S): A baseline ovarian cyst on cycle day 3 was associated with a poorer outcome after IVF-ET. PMID- 9988398 TI - Survey of genetic screening for oocyte donors. AB - OBJECTIVE: To describe current screening practices of oocyte donation programs in the Society for Assisted Reproductive Technologies (SART). DESIGN: Descriptive data from a mailed questionnaire. SETTING: Academic medical center. PARTICIPANT(S): In vitro fertilization programs in SART. INTERVENTION(S): Survey mailed to IVF programs in the SART registry. MAIN OUTCOME MEASURE(S): Current practices, opinions, and genetic criteria for oocyte donor selection. RESULT(S): Results from 159 of 229 (69%) eligible oocyte donation programs are described. Most centers (70%) completed fewer than 25 cycles and used both anonymous and directed donors. There was considerable variability in limits on numbers of cycles or births allowed per donor, with many centers having no limits. As well, the use of well-established screening tests for genetic disorders, such as sickle cell anemia and cystic fibrosis, varied considerably. Consultation with a geneticist was possible at most (89%) centers and specifically mentioned by some centers as a means to help make decisions. CONCLUSION(S): Most programs follow recommendations made by the American Society of Reproductive Medicine (ASRM) for screening of gamete donors, but a significant percentage does not use well established testing. The widespread availability of genetic consultation should promote responsible screening practices. PMID- 9988399 TI - Risk factors for ectopic pregnancy in assisted reproduction. AB - OBJECTIVE: To identify risk factors for ectopic pregnancy (EP) after IVF-ET. DESIGN: Retrospective cohort study. SETTING: In vitro fertilization clinic at a university hospital. PATIENT(S): A total of 725 women who conceived after IVF were studied with regard to background factors, indications for IVF, and factors related to the IVF procedure through review of their medical charts. The rate of EP was 4%, corresponding with 29 EPs, of which 2 were heterotopic. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Pregnancy outcome, defined as intrauterine pregnancy or EP. Background factors, indications for IVF, and factors related to the IVF procedure were analyzed for possible correlation with the outcome of EP. Risk factors for EP were identified by logistic regression analysis. RESULT(S): Tubal factor infertility, various previous abdominal surgeries, previous EP or pelvic infection, presence of a hydrosalpinx or fibroid, and type of transfer catheter used showed a positive correlation with EP as outcome. Logistic regression analysis identified two factors with predictive power: tubal factor infertility and previous myomectomy. CONCLUSION(S): Tubal factor infertility was the most prominent risk factor for EP after IVF. Previous myomectomy appeared to be another important risk factor, but this is a new finding that needs to be confirmed by further study. PMID- 9988400 TI - Serum vascular endothelial growth factor concentrations in in vitro fertilization cycles predict the risk of ovarian hyperstimulation syndrome. AB - OBJECTIVE: To explore the value of serum vascular endothelial growth factor (VEGF) concentrations during IVF cycles in predicting the risk of ovarian hyperstimulation syndrome (OHSS). DESIGN: Prospective study. SETTING: London Women's Clinic. PATIENT(S): One hundred seven women undergoing IVF. Mild OHSS developed in 10 women, moderate OHSS in 7, and severe OHSS in 3. INTERVENTION(S): Serum VEGF concentrations were measured before treatment, after pituitary desensitization, and on the days of hCG administration, oocyte collection, and ET. MAIN OUTCOME MEASURE(S): Serum VEGF concentrations. RESULT(S): Serum VEGF concentrations were higher in women in whom OHSS developed. The increase in the VEGF concentration that occurred between the day of hCG administration and the day of oocyte collection (the "VEGF rise") was an important marker of OHSS. The VEGF rise was higher in women in whom OHSS developed. A higher VEGF rise predicted all cases of OHSS and moderate/severe cases of OHSS with a sensitivity of 100% and a specificity of 60%. A likelihood ratio test showed that adding the VEGF rise or the VEGF concentration on the day of oocyte collection to a regression model as a continuous variable to the number of follicles, the E2 concentration, and the presence of polycystic ovaries significantly contributed to predicting the risk of OHSS. CONCLUSION(S): The results support the role of VEGF as an important nonsteroidal index of ovarian response. The VEGF rise may have an advantage over the E2 concentration, the number of follicles, and the number of oocytes, which individually predict only 15%-25% of cases of OHSS. PMID- 9988401 TI - Withholding gonadotropins ("coasting") to minimize the risk of ovarian hyperstimulation during superovulation and in vitro fertilization-embryo transfer cycles. AB - OBJECTIVE: To evaluate superovulation (SOV) and IVF-ET cycles in which E2 levels were allowed to decrease to restrain rapid follicular growth and minimize the risk of ovarian hyperstimulation syndrome. DESIGN: Retrospective series. SETTING: Tertiary care infertility practice. PATIENT(S): Women who underwent SOV (n = 51) and IVF-ET (n = 93) treatment and who were at risk for OHSS. INTERVENTION(S): In SOV cycles, hMG was withheld (coasting) for >3 days before hCG administration, until follicular maturity was attained (> or = 3 follicles of > or = 18 mm) and E2 levels decreased. In IVF-ET cycles, either follicular maturity was attained before coasting (n = 63), allowing hCG administration after E2 levels decreased by >25%, or coasting occurred before follicular maturation (n = 30), necessitating the administration of additional hMG after coasting. MAIN OUTCOME MEASURE(S): Estradiol concentrations, follicle size, and pregnancy rates. RESULT(S): Estradiol concentrations usually rose for > or = 1 day after coasting began, then fell by > or = 25% while follicle numbers and mean diameters increased. No spontaneous LH surges occurred, although four SOV cycles were canceled because of excessive follicular development. Of the women who received hCG,11 of 47 (23% per cycle) conceived during SOV and 35 of 93 (37.6% per cycle) conceived during IVF-ET. Severe ovarian hyperstimulation syndrome developed in 1 woman who underwent IVF-ET. CONCLUSION(S): Coasting can safely rescue overstimulated SOV and IVF-ET cycles characterized by an excessive rise in E2 levels and/or numerous incompletely mature follicles. PMID- 9988402 TI - Is there a risk of cytomegalovirus transmission during in vitro fertilization with donated oocytes? AB - OBJECTIVE: To define the risk of human cytomegalovirus (HCMV) transmission from donated oocytes. DESIGN: Prospective study. SETTING: University IVF program. PATIENT(S): Sixty-seven couples undergoing 72 cycles of IVF-ET. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Serum from both partners (women: n = 71; men: n = 60) was obtained for detection of antibodies to HCMV. Semen before preparation (n = 53), sperm after preparation (Percoll gradient; n = 47), cervical mucus aspirated at the time of oocyte aspiration (n = 70), and uninseminated oocytes and embryos not suitable for cryopreservation (n = 568) were frozen in liquid nitrogen. Polymerase chain reaction was used for detection of HCMV (immediate early 1 gene) in all samples collected. RESULT(S): Serum antibodies to HCMV were found in 62% of the women and 37% of the men tested. Human cytomegalovirus DNA was detected in 25% of the ejaculates and in 19% of the cervical mucus samples. There was no amplification of HCMV DNA from oocytes or embryos. CONCLUSION(S): Because we were unable to amplify HCMV DNA from any of the oocytes or embryos, it seems unlikely that HCMV is transmissible through oocyte or embryo donation. PMID- 9988403 TI - Three-dimensional partial zona dissection for preimplantation genetic diagnosis and assisted hatching. AB - OBJECTIVE: To develop a new approach to partial zona dissection of oocytes and embryos for facilitating preimplantation genetic sampling and assisted hatching. DESIGN: Controlled clinical study. SETTING: Preimplantation genetic diagnosis and IVF program, Reproductive Genetics Institute/IVF Illinois, Chicago, Illinois. PATIENT(S): Three hundred forty patients undergoing IVF in whom preimplantation genetic diagnosis or assisted hatching was required. INTERVENTION(S): Three dimensional partial zona dissection and conventional partial zona dissection were performed, with the use of a simple microneedle, on embryos before preimplantation genetic sampling or on day 3 of embryo development before ET. MAIN OUTCOME MEASURE(S): Pregnancy rate, implantation rate, and ease of preimplantation genetic sampling. RESULT(S): A pregnancy rate of 42% and an embryo implantation rate of 17.6% were obtained in the group in which three dimensional partial zona dissection was performed, compared with a pregnancy rate of 33% and an implantation rate of 14.7% in the control group, which underwent conventional partial zona dissection. Preimplantation genetic sampling can be performed without distortion of the blastomere configuration in the embryo. CONCLUSION(S): Three-dimensional partial zona dissection is a safe and simple mechanical means of creating an opening sufficient for the atraumatic removal of material from oocytes and embryos for preimplantation genetic diagnosis and assisted hatching. PMID- 9988404 TI - Effect of chronic administration of cabergoline on uterine perfusion in women with polycystic ovary syndrome. AB - OBJECTIVE: To confirm whether patients with polycystic ovary syndrome (PCOS) have a reduction in uterine perfusion and to verify whether chronic administration of cabergoline can decrease this high vascular resistance. DESIGN: Prospective randomized trial. SETTING: Endocrinological Centre of the Department of Obstetrics and Gynecology, University of Cagliari, Cagliari, Italy. PATIENT(S): Thirty patients were enrolled in the study: 20 affected by PCOS and 10 healthy controls. Patients with PCOS were randomly assigned to one of two treatments for 3 months: oral administration of cabergoline (0.5 mg) every week or oral administration of placebo every week. INTERVENTION(S): All patients underwent transvaginal ultrasonography associated with Doppler flow measurement of the uterine artery, and serum hormone concentrations were determined during the early follicular phase. In women with PCOS, Doppler flow measurement and hormonal assessment were repeated in the early follicular phase of the third month of treatment. MAIN OUTCOME MEASURE(S): Pulsatility index of the uterine artery before and during treatment. RESULT(S): The mean pulsatility index of the uterine artery in patients with PCOS was significantly higher than that of the control group (3.29+/-0.5 and 2.01+/-0.2, respectively). Patients with PCOS treated with cabergoline showed a significant increase in uterine perfusion, with a pulsatility index of 3.14+/-0.6 before and 2.39+/-0.5 during the treatment. No difference was found in patients with PCOS treated with placebo. CONCLUSION(S): Patients with PCOS have high resistance in the uterine arteries, but chronic administration of cabergoline can increase uterine perfusion. PMID- 9988405 TI - Do hyperandrogenic women with normal menses have polycystic ovary syndrome? AB - OBJECTIVE: To determine the prevalence of polycystic ovary syndrome (PCOS) among hyperandrogenic women who report normal menses. DESIGN: Prospective observational study. SETTING: Academic practice in reproductive endocrinology. PATIENT(S): Fifty-eight consecutively seen new patients with hyperandrogenism who reported normal menses. INTERVENTION(S): Ovulatory status was assessed with timed serum progesterone measurements. The following tests also were carried out: vaginal ultrasound examination; measurement of the ovarian response of 17 hydroxyprogesterone (17-OHP) after the administration of leuprolide acetate, 1 mg SC; and determination of fasting serum LH, FSH, E2, 17-OHP, insulin, and androgen levels. MAIN OUTCOME MEASURE(S): Determination of ovulatory status, polycystic appearance of ovaries, and increased response of 17-OHP to leuprolide acetate. RESULT(S): Twelve (20.7%) of the hyperandrogenic women were anovulatory and met the usual criteria for the diagnosis of PCOS. The ovulatory patients had lower serum total and unbound testosterone levels. Thirty-one (53.4%) of the ovulatory women had polycystic ovaries on ultrasound examination and/or an increased 17-OHP response to leuprolide acetate, suggesting the diagnosis of PCOS despite the presence of ovulation. Considering both the anovulatory and ovulatory patients, 74% of the hyperandrogenic women studied could have PCOS. CONCLUSION(S): The data suggest that most (74%) hyperandrogenic women who report normal menses have evidence for the diagnosis of PCOS. PMID- 9988406 TI - Effect of troglitazone on endocrine and ovulatory performance in women with insulin resistance-related polycystic ovary syndrome. AB - OBJECTIVE: To investigate the effect of troglitazone, a new antidiabetic agent that improves insulin resistance, on endocrine, metabolic, and ovulatory performance in women with insulin resistance-related polycystic ovary syndrome (PCOS). DESIGN: Prospective clinical study. SETTING: Infertility outpatient clinic, Niigata University Hospital, Niigata, Japan. PATIENT(S): Thirteen women with PCOS and insulin resistance. INTERVENTION(S): Troglitazone (400 mg/d) was administered for 12 weeks. MAIN OUTCOME MEASURE(S): Insulin and other hormone (gonadotropins, androgens) levels; various parameters relating to glucose and lipid metabolism before, during, and after troglitazone administration; and ovulation rate. RESULT(S): The mean (+/-SD) fasting insulin concentration was significantly reduced, from 18.3+/-8.9 to 10.5+/-7.1 microU/mL. The LH level was reduced from 9.7+/-3.4 to 4.8+/-3.9 mIU/mL and the testosterone level was reduced from 0.9+/-0.5 to 0.5+/-0.3 ng/mL in accordance. Atherosclerotic lipid levels also were normalized. Before troglitazone administration, the ovulation rate during clomiphene citrate therapy was 34.9% per cycle (15/43). This increased significantly to 72.7% (8/11) during troglitazone coadministration. Further, an ovulation rate of 42.3% (11/26) was achieved with troglitazone alone. CONCLUSION(S): In women with PCOS and insulin resistance, the reduction of hyperinsulinemia that is produced by troglitazone improves the hyperandrogenism that characterizes PCOS, restoring ovulation. PMID- 9988407 TI - Increased expression of messenger ribonucleic acid encoding cytochrome P450 cholesterol side-chain cleavage and P450 17alpha-hydroxylase enzymes in ovarian hyperthecosis. AB - OBJECTIVE: To investigate whether the increased ovarian androgen synthesis in hyperthecosis is due to increased expression of the steroidogenic enzymes essential for androgen synthesis. DESIGN: Controlled study to investigate concentration of steroidogenic enzymes in the ovarian stroma of women with hyperthecosis of the ovaries. SETTING: Academic research environment. PATIENT(S): Three women with ovarian hyperthecosis and eight with normal ovulatory cycles. INTERVENTION(S): Ovarian stromal tissues were obtained from women with hyperthecosis and women with normal ovaries. Diagnosis of hyperthecosis was confirmed by histologic examination of the ovaries. Steroid levels were measured in the ovarian vein serum of one patient with hyperthecosis. MAIN OUTCOME MEASURE(S): Tissues were frozen immediately in liquid nitrogen and kept frozen until RNA was extracted. Total RNA was examined by Northern blot analysis using 32P-labeled complementary DNA (cDNA) probes encoding human P450scc and P450(17alpha) enzymes. RESULT(S): P450scc and P450(17alpha) messenger RNAs (mRNAs) were detected in the normal ovarian stroma and stromal hyperthecosis. Compared with normal ovarian stroma, P450scc mRNA was increased twofold and P450(17alpha) mRNA was increased threefold in stromal hyperthecosis. CONCLUSION(S): [1] Ovarian stroma is probably the site of androgen production in ovarian hyperthecosis. [2] Increased stromal androgen synthesis in hyperthecosis could be due to increased expression of the enzymes P450scc and P450(17alpha) in the ovarian stroma. [3] Markedly increased concentrations of 17alpha hydroxyprogesterone in the ovarian vein serum indicate possible dysregulation of P450(17alpha) in ovarian hyperthecosis. PMID- 9988408 TI - Cytogenetic diagnosis of "normal 46,XX" karyotypes in spontaneous abortions frequently may be misleading. AB - OBJECTIVE: To use the molecular identification of Y chromosome material in products of conception cytogenetically diagnosed as "46,XX" to confirm the occurrence of inaccurate cytogenetic test results most likely attributable to maternal cell contamination. DESIGN: Retrospective analysis. SETTING: Academic medical center. PATIENT(S): Thirty-four archival tissues from cases of spontaneous abortion with a "46,XX" karyotype based on cytogenetic analysis. INTERVENTION(S): Maternal and villus DNA were extracted from microdissected, formalin-fixed, paraffin-embedded archival tissues. The presence of the X and Y chromosomes was detected with the use of polymerase chain reaction assays and confirmed with fluorescence in situ hybridization. MAIN OUTCOME MEASURE(S): Accuracy of cytogenetic evaluation of products of conception. RESULT(S): Four (29%) of 14 first trimester and 1 (5%) of 20 second trimester "46,XX" pregnancy losses contained Y chromosome-specific DNA and demonstrated a single X chromosome specific allele by polymerase chain reaction analysis consistent with an "XY" karyotype. Fluorescence in situ hybridization was confirmatory in 4 of 5 samples that demonstrated single X and Y signals in villus cells. CONCLUSION(S): Inaccuracy exists in the cytogenetic analysis of early products of conception that most likely is due to maternal cell contamination. In the absence of confirmatory testing, such as with a "DNA fingerprinting" assay, reports of a "46,XX" karyotype should be used cautiously in patient counseling and management. PMID- 9988409 TI - Antiphospholipid antibodies inhibit prostaglandin release by decidual cells of early pregnancy: possible involvement of extracellular secretory phospholipase A2. AB - OBJECTIVE: To investigate the effect of antiphospholipid antibodies on eicosanoid production by human decidual cells and the in vitro interaction between antiphospholipid antibodies and secretory phospholipase A2. DESIGN: Cultures of human decidual cells from early pregnancy. SETTING: All decidual specimens were obtained from the Obstetrics and Gynecology Department of the Catholic University, Rome, Italy. PATIENT(S): Patients were undergoing operative laparoscopy for extrauterine pregnancy, with a period of amenorrhea ranging from 6 to 9 weeks. INTERVENTION(S): Decidual samples were collected at laparoscopy by routine uterine curettage. MAIN OUTCOME MEASURE(S): Decidual cells were incubated with antiphospholipid antibodies, and eicosanoids (prostaglandin [PG] E2, PGF2alpha, and thromboxane B2) were assayed by RIA after 24 hours of culture. In vitro interactions between antiphospholipid antibodies and secretory phospholipase A2 were investigated with use of a modified ELISA for phospholipase A2. RESULT(S): Antiphospholipid antibodies reduced eicosanoid release from decidual cells in a dose-dependent fashion. In vitro assays showed that antiphospholipid antibodies bound secretory phospholipase A2 and that a competition occurred between antiphospholipid antibodies and secretory phospholipase A2 for the common substrate cardiolipin. CONCLUSION(S): In light of the critical role played by eicosanoids in decidual function, we suggest that an interaction between antiphospholipid antibodies and secretory phospholipase A2 occurring in vivo might impair important cellular communications at the decidual level in the antiphospholipid antibody syndrome. PMID- 9988410 TI - Expression of integrin messenger ribonucleic acid in human endometrium: a quantitative reverse transcription polymerase chain reaction study. AB - OBJECTIVE: To assess the expression of selected integrin subunit's messenger RNA (mRNA) in human endometrium during the menstrual cycle. DESIGN: A prospective comparative study. SETTING: Academic research environment. PATIENT(S): Premenopausal women with histologically normal endometrium who were undergoing hysterectomy. INTERVENTION(S): Endometrial tissues were collected. RESULT(S): Human endometrium expresses integrins alpha2, alpha3, alpha4, alpha5, alpha6.1, alpha6.2, alpha v, beta1, beta2, beta3, and beta5, as well as fibronectin mRNA. The levels of endometrial integrins mRNA expression varied significantly, with the lowest levels observed for alpha2, beta3, and fibronectin and the highest for alpha5, beta2, and beta5. The levels of integrins alpha2, alpha3, and alpha5 mRNA expression were significantly higher during the proliferative phase, whereas alpha4, alpha6.2, alpha v, beta1, beta2, beta3, beta5, and fibronectin were higher during the secretory phase of the menstrual cycle. The alpha6.1 mRNA was found to be equally expressed in the endometrium during the menstrual cycle, whereas the most dramatic changes occurred in alpha v and beta3 expression, compared with other integrin subunits. CONCLUSION(S): Human endometrium expresses mRNA for several integrins and fibronectin, with up-regulation of alpha4, alpha v, beta1, and beta3 during the secretory phase of the menstrual cycle, suggesting that their differential expression may be regulated in part by ovarian steroids. PMID- 9988411 TI - Arylhydrocarbon receptor expression in the human endometrium. AB - OBJECTIVE: To determine the expression and localization of the arylhydrocarbon (dioxin) receptor in human endometrium throughout the normal menstrual cycle. DESIGN: Retrospective immunohistochemical and in situ hybridization study. SETTING: Academic research unit. PATIENT(S): Premenopausal women (n = 86), aged 25 to 45 years, with histologically normal endometrium undergoing curettage or hysterectomy. INTERVENTION(S): Endometrial samples were collected from days 3 to 26 of the cycle by superficial scrapings of the uterine cavity or by hysterectomy. MAIN OUTCOME MEASURE(S): Expression of arylhydrocarbon receptor mRNA and protein. RESULT(S): Arylhydrocarbon receptor was expressed in 43% of the endometria studied and was correlated with the day of the cycle. The maximum of immunopositive endometria was found around the time of ovulation. Immunostaining decreased with increasing age of the patients. The receptor protein was localized exclusively in the apical part of the cytoplasm in the epithelial cells of the endometrial glands. In women positive for arylhydrocarbon receptor, arylhydrocarbon receptor mRNA was expressed in the cytoplasm of endometrial epithelial cells. CONCLUSION(S): Our results describe the expression of the arylhydrocarbon receptor in human endometrium and indicate a possible involvement of this transcription factor in endometrial function in women during the reproductive phase. PMID- 9988412 TI - Human endometrial stromal cells improve embryo quality by enhancing the expression of insulin-like growth factors and their receptors in cocultured human preimplantation embryos. AB - OBJECTIVE: To demonstrate the mechanism by which human endometrial stromal cells improve embryo quality in coculture. DESIGN: Randomized study. SETTING: Academic research center. PATIENT(S): Patients undergoing IVF-ET. INTERVENTION(S): Donated human embryos were cultured randomly either alone (group A) or with human endometrial stromal cells (group B), and the embryonic expression of insulin-like growth factors (IGFs) and their receptors was detected by reverse transcriptase polymerase chain reaction after culture. MAIN OUTCOME MEASURE(S): The embryo frequency distribution of groups A and B before and after culture and the embryonic transcripts of the IGF family genes of the two study groups after culture were compared. RESULT(S): The embryo frequency distribution of the day 3 embryonic stages in groups A and B was not different. However, after culture, a statistically significant difference in blastocyst formation was observed between groups A and B. A significant increase in the expression of IGF-1, IGF-2, the IGF 1 receptor, and the insulin-receptor also was noted. Among the embryos that reached the blastocyst stage, the expression of IGF-1 and the IGF-1 receptor also was significantly different in the two study groups. CONCLUSION(S): Human endometrial stromal cells enhanced the expression of IGFs and their receptors in cocultured human embryos, which may be essential for improving embryo quality. PMID- 9988413 TI - Messenger ribonucleic acid for the gonadal luteinizing hormone/human chorionic gonadotropin receptor is not present in human endometrium. AB - OBJECTIVE: To determine whether messenger RNA for the gonadal LH/hCG receptor is present in human endometrium with the use of reverse-transcriptase polymerase chain reaction. DESIGN: In vitro experiment. SETTING: Academic medical center. PATIENT(S): Premenopausal women who were not receiving hormonally active medications and who were undergoing hysterectomy for uterine leiomyomas, menorrhagia, pelvic pain, or uterine prolapse. INTERVENTION(S): Tissue from hysterectomy specimens was processed for RNA and treated with deoxyribonuclease where appropriate, and RNA was reverse-transcribed to complementary DNA. MAIN OUTCOME MEASURE(S): An appropriately sized band after reverse-transcriptase polymerase chain reaction, followed by sequencing to confirm the results. RESULT(S): A primer pair that spanned the extracellular domain was unable to amplify receptor complementary DNA from human endometrial tissue. For a primer pair that spanned transmembrane regions 2-6 of the receptor and was contained wholly in exon 11, a 552-base pair fragment was amplified successfully in 19 of 25 human endometrial samples. CONCLUSION(S): The traditional gonadal LH/hCG receptor does not appear to be present in human endometrial tissue. The presence of a portion of the transmembrane part of the molecule suggests that human endometrium may express a truncated or variant form of the receptor. PMID- 9988414 TI - A case of fatal pulmonary thromboembolism associated with the use of intravenous estrogen therapy. AB - OBJECTIVE: To report a case of fatal pulmonary embolism associated with the use of i.v. estrogen therapy for menometrorrhagia. DESIGN: Case report. SETTING: University hospital. PATIENT(S): A 52-year-old woman with fibroid uterus treated with GnRH analogues with add-back therapy who presented with excessive vaginal bleeding. INTERVENTION(S): Intravenous conjugated estrogens were administered for a total of six doses. MAIN OUTCOME MEASURE(S): Fatal thromboembolic event. RESULT(S): The day after i.v. conjugated estrogens were administered, the patient had only scant vaginal bleeding, but she experienced the sudden onset of respiratory distress, became comatose, and subsequently had ventricular fibrillation leading to asystole. All resuscitative efforts failed. Postmortem examination revealed bilateral pulmonary artery thromboembolism (saddle embolus). CONCLUSION(S): Intravenous conjugated estrogen therapy may be complicated by fatal thromboembolic events. This potential adverse effect must be considered in the use of such therapy for severe menometrorrhagia, especially when treating a patient at increased risk. PMID- 9988415 TI - Laparoscopic vesicopsoas hitch for infiltrative ureteral endometriosis. AB - OBJECTIVE: To report the technique and outcome of a laparoscopic vesicopsoas hitch used for the treatment of infiltrative ureteral endometriosis. DESIGN: Case report. SETTING: A tertiary care center. PATIENT(S): A 36-year-old woman with infiltrative endometriosis of the ureter. INTERVENTION(S): A laparoscopic vesicopsoas hitch. MAIN OUTCOME MEASURE(S): The return of normal ureteral function as measured by IV pyelography and ultrasonography. RESULT(S): After partial ureteral resection, it was noted that a tension-free anastomosis to the bladder was not possible. Thus, a laparoscopic vesicopsoas hitch was performed. CONCLUSION(S): A vesicopsoas hitch can be performed successfully by laparoscopy. PMID- 9988416 TI - Multifetal pregnancy reduction: modification of the technique and analysis of the outcome. AB - OBJECTIVE: To modify the technique of multifetal pregnancy reduction and to study the outcome of reduced twins in comparison with nonreduced twins and high-order multiple gestations. DESIGN: Prospective controlled study. SETTING: The Egyptian IVF-ET Center, Cairo. PATIENT(S): Seventy-five patients with high-order multiple pregnancies resulting from assisted reproduction. Controls were 40 nonreduced twin pregnancies and 22 high-order multiple gestations. INTERVENTION(S): Transvaginal ultrasonically guided multifetal pregnancy reduction was performed. The first 30 cases were done using KCl as a cardiotoxic agent. The modified technique was used for the last 45 cases at an earlier gestational age (approximately 7 weeks) by eliminating the use of KCI and by aspirating the embryonic parts. MAIN OUTCOME MEASURE(S): Miscarriage rate, gestational age at delivery, birth weight, and pregnancy complications. RESULT(S): Using the modified technique, the miscarriage rate was 8.8% and 41 patients delivered between 32 and 39 weeks of gestation (mean+/-SD, 36.9+/-2.45 weeks). The mean (+/ SD) birth weight was 2,450.51+/-235.44 g. The miscarriage rate, fetal wastage rate, mean gestational age, and mean birth weight were similar in reduced and nonreduced twins and were significantly better than in nonreduced triplets and quadruplets. CONCLUSION(S): The modified technique of multifetal pregnancy reduction significantly improved outcomes, which were similar to those of nonreduced twins resulting from assisted reproduction and significantly better than those of nonreduced triplets and quadruplets. PMID- 9988417 TI - Endocrine function in transplanted ovaries? PMID- 9988418 TI - Endocrine function in transplanted ovaries? PMID- 9988419 TI - Does intravenous albumin prevent severe ovarian hyperstimulation syndrome? PMID- 9988420 TI - HRT and cardiovascular risk factors? PMID- 9988421 TI - "Poor responders" to gonadotropins and levels of antibodies to Chlamydia trachomatis? PMID- 9988422 TI - Meta-analysis for the diagnostic accuracy of a test? PMID- 9988423 TI - Meta-analysis for the diagnostic accuracy of a test? PMID- 9988424 TI - Sleepless nights for SART investigators? PMID- 9988425 TI - Sleepless nights for SART investigators? PMID- 9988426 TI - Sleepless nights for SART investigators? PMID- 9988427 TI - Is allergy increasing?--early life influences. AB - Data from epidemiological studies conducted in several countries worldwide have revealed that the prevalences of allergic conditions, including allergic rhinitis, asthma and eczema, have increased from the 1940s/50s to the 1990s. These allergic conditions involve specific IgE-mediated responses, and a few studies have demonstrated that IgE levels have increased in some communities over time in a manner similar to the incidences of allergic conditions. The predisposition for atopy appears to be determined in early life, and evidence indicates that events occurring in utero and in infancy can influence the future development of atopy. The intrauterine environment favours TH2 cell development and IgE production and could predispose to atopy. It can be hypothesized that dietary or other factors favouring TH2 proliferation might contribute to the development of atopic disease. Conversely, early infection has been found to have a negative association with the development of atopy, perhaps through promotion of a TH response; the reduction in infection in the very young as a consequence of modern healthcare may have contributed to the increase in atopic disease. Thus, it is a plausible hypothesis that changes in the conditions of the intrauterine environment and/or in infancy (for example, in nutrition and in rates of infection) may explain the observed increases in atopy and allergic conditions. PMID- 9988428 TI - Why is allergy increasing?--environmental factors. AB - Data from epidemiological studies have shown that allergic conditions have increased over the last 30-40 years, particularly in developed countries, despite a decrease in the severity of grass pollen seasons. Other epidemiological studies suggest an interaction between allergic diseases and traffic pollution, and laboratory findings indicate that diesel exhaust particles enhance sensitivity to allergens. In an in vitro study, we found evidence to suggest that cigarette smoke may render the airway epithelium more susceptible to adverse effects of allergens. Evidence from other studies indicates that O3 and NO2, with or without SO2, can enhance the airway allergic response in susceptible individuals such as those with asthma and rhinitis. Studies investigating cellular and subcellular mechanisms suggest that pollutants are likely to influence the actions and interactions of a variety of cells, and lead to the synthesis of proinflammatory mediators that modulate the activity and functions of inflammatory cells. PMID- 9988429 TI - Histamine--a major role in allergy? AB - Since its discovery in 1911, histamine has been recognized as a major mediator in allergic reactions and diseases, and today antihistamines remain important agents in the treatment of these conditions. In addition to its known effects on glands, vessels and sensory nerves, recent data have provided further evidence of histamine's proinflammatory actions, which appear to be mediated mainly by H1 receptors. Thus, findings indicate that histamine is a crucial mediator in both the early and late-phase reactions of an allergic response, playing important roles in cytokine release and in the adhesion process. Histamine has been shown to increase the adhesion of leucocytes to the endothelium and to stimulate production of IL-6 and IL-8 by endothelial cells. It also increases TNF alpha induced IL-6 production and expression of adhesion molecules. These effects can be inhibited by H1 receptor antagonists. First-generation antihistamines, though moderately effective, showed poor selectivity and caused sedation, due to their penetration of the blood-brain barrier, and other troublesome side-effects. Second-generation antihistamines such as ebastine have increased potency due to greater selectivity for histamine receptors, and improved tolerability due to lack of penetration of the blood brain barrier. Recent studies have shown ebastine 10 mg daily to be effective, safe and well tolerated in the treatment of seasonal allergic rhinitis (SAR), with a rapid onset of action, symptom relief comparable to that seen with topical azelastine or oral loratadine 10 mg o.d., cetirizine 10 mg o.d. or terfenadine 60 mg b.i.d., and no significant side effects. Ebastine therefore offers a new option in the treatment of seasonal allergic rhinitis. PMID- 9988430 TI - The inflammatory nature of allergic disease. AB - The allergic inflammatory response in allergic rhinitis has been studied extensively owing to the high frequency of the condition, the significant morbidity it causes and the accessibility of the nasal tissue. The allergic inflammatory response is characterized by IgE synthesis, IgE-dependent mast cell activation and infiltration of the nasal mucosa by T lymphocytes and eosinophils. The immediate-phase response is mediated by a range of inflammatory mediators (such as histamine, leukotrienes and prostaglandins), resulting in vasodilatation, oedema, mucus secretion, itching and sneezing. Individuals who experience a late-phase response have further nasal symptoms 4-24 h after the initial challenge with allergen. Results of nasal biopsy studies indicate that the late-phase allergic response involves T-lymphocyte activation, production of TH2-type cytokines and tissue eosinophilia. Corticosteroids potently inhibit T lymphocyte responses, and clinical studies in subjects with allergic rhinitis have demonstrated that they are extremely effective in blocking both early- and late-phase allergic reactions. Topical aqueous triamcinolone acetonide nasal spray represents a novel formulation of a topical corticosteroid for the treatment of allergic rhinitis. Data from controlled clinical studies indicate that it is effective in treating seasonal and perennial disease, is well tolerated, does not suppress adrenocortical function, is odourless, and can be administered as a once-daily dose. PMID- 9988431 TI - Allergic rhinitis--making the correct diagnosis. AB - The symptoms of rhinosinusitis occur in a variety of sinonasal conditions, which may be broadly classified as allergic (seasonal, perennial or occupational rhinitis/rhinosinusitis) or non-allergic (caused by infection, or non-infectious, e.g. drug-induced or idiopathic). Correct diagnosis is important for optimal management. A thorough history should be taken, followed by general and endoscopic examinations and confirmatory investigations. Careful examination should reveal obvious alternative causes of symptoms, such as polyps or tumours. If allergy is suspected, this can be confirmed by further tests, particularly the skin-prick test or measurements of serum specific IgE. Imaging techniques, usually X-rays or CT scanning, are of use if a systemic condition or major sinonasal disorder needs to be excluded. Other useful diagnostic aids are measurements of nasal peak flow, rhinomanometry, acoustic rhinometry, olfactory threshold, and measures of mucociliary function (which may include biopsy for electron microscopy). PMID- 9988432 TI - Management of rhinitis--the specialist's opinion. AB - The aim of the guidelines in the International Consensus Report on the Diagnosis and Management of Rhinitis was to aid general practitioners (GPs) in the treatment of mild or moderate cases of seasonal allergic rhinitis (SAR), perennial allergic rhinitis (PAR) and non-allergic rhinitis. After the initial strategy of allergen avoidance, GPs have several medications at their disposal. For mild or occasional symptoms of SAR, an oral H1-antihistamine or topical antihistamines or chromones are advised. For moderate symptoms, a topical nasal steroid can be used with or without an oral H1-antihistamine supplemented if necessary with a topical antihistamine or chromone eyedrops. For PAR, patients should be advised on how to minimize their exposure to house-dust mite (HDM) allergens. For intermittent symptoms, an oral H1-antihistamine and an occasional oral decongestant can be used. For persistent symptoms, a topical nasal steroid is advised, possibly supplemented with an antihistamine. For non-allergic rhinitis, irritant factors should be identified and avoided if possible. Topical or oral decongestants can be used for intermittent symptoms. Topical ipratropium bromide is useful for drying up watery rhinorrhea. For moderate symptoms, either a topical nasal steroid or topical ipratropium bromide should be used. For all the conditions, if treatment proves ineffective and symptoms are severe, then a specialist referral is appropriate. Investigations are conducted to identify causative allergens. Further treatment options include immunotherapy and minimal invasive surgery. A large clinical study is ongoing to validate the guidelines and enable the development of simpler therapeutic options according to symptom severity. In the meantime, the current guidelines provide a valuable guide to both the GP and the specialist. PMID- 9988433 TI - Rhinitis management: the patient's perspective. AB - Seasonal allergic rhinitis causes considerable impairment of health-related quality of life (HQRL). Generic quality-of-life questionnaires enable a comparison to be made between patients with different illnesses, but they often have insufficient depth to measure specific problems that are important to an individual with a particular condition. In order to overcome these shortcomings, the Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) was developed. Eighty-nine patients, with a wide range of rhinoconjunctivitis severity, scored a list of 91 problems for importance. The highest-scoring problems were the practical problems: continually having to blow the nose, rub the nose and eyes, and carry tissues. Patients were also bothered by sleep impairments and systemic problems such as tiredness, poor concentration and thirst. Questionnaires have also been developed for adolescents (12-17 years of age)--finding similar results to those for adults--and children (6-12 years of age), who were troubled by their symptoms but did not have the emotional dysfunction experienced by adults and adolescents. All three questionnaires have strong measurement properties and have high reliability and good responsiveness, validity and interpretability. Quality of-life questionnaires can be used in clinical studies to help elucidate which treatments are preferred by patients and the efficacy of treatment regimens. Disease-specific quality-of-life questionnaires can also be used during routine assessments and may reveal problems not spontaneously volunteered by patients, particularly children. Results can also be compared at each clinic visit to determine whether each intervention has been beneficial. PMID- 9988434 TI - Allergic eye disease--a clinical challenge. AB - Currently, six basic allergic eye diseases are recognized. In seasonal (SAC) and perennial allergic conjunctivitis (PAC), the allergic response is mediated predominantly by mast cells, whereas the more severe conditions, vernal (VKC) and atopic keratoconjunctivitis (AKC) and giant papillary conjunctivitis (GPC), are associated with a preponderance of T cells. Acute allergic conjunctivitis (AAC) occurs when a large quantity of allergen inoculates the eye and is usually self limiting. SAC, the most common ocular allergy, is the ocular component of hayfever. PAC in the UK is most commonly caused by the house-dust mite (HDM); diagnosis is confirmed by skin-prick tests, eosinophils in the conjunctival smear, and raised tear or serum total IgE. SAC and PAC can usually be managed with chromone eyedrops and antihistamines. VKC usually presents in children under 10 years of age and mainly affects boys. Sufferers frequently have a personal or family history of atopy. Corneal involvement can occur in VKC, making it potentially sight-threatening. AKC occurs in atopic adults, and like VKC it affects the cornea. VKC and AKC require steroid treatment under specialist supervision; minimization of the steroid dose can often be achieved with use of a chromone. GPC occurs due to repeated contact of the conjunctival surface with a foreign surface, such as contact lenses. Attention to lens hygiene or switching to different lenses and treatment with a chromone are frequently effective. In all allergic eye diseases contact with the precipitating allergen should be avoided as far as possible. PMID- 9988435 TI - Treating severe eye allergy. AB - Allergic eye conditions, particularly seasonal allergic conjunctivitis (SAC), are common. Itching, oedema and hyperaemia are relieved with topical H1-antagonists or sodium cromoglycate. The newer mast-cell stabilizing agent nedocromil sodium has a similar safety profile to sodium cromoglycate, but is more potent and has a more convenient twice-daily dosing regimen. When several placebo-controlled studies of its use in the treatment of SAC were analysed, it was found that 80% of patients reported symptom relief. In a further study, nedocromil sodium eyedrops (twice-daily dosing) had similar overall efficacy to sodium cromoglycate eyedrops (four-times-daily dosing) in subjects with SAC during the birch season, but during the period of highest pollen challenge, only the former agent was significantly more effective than placebo. Another study found that nedocromil sodium had efficacy equivalent to levocabastine over 7 days, but tended to have a more rapid onset of action. In patients with perennial allergic conjunctivitis (PAC) unresponsive to sodium cromoglycate, both clinicians and patients reported significantly better control of symptoms with nedocromil sodium eyedrops than with placebo. Recently, in a long-term study of treatment for vernal keratoconjunctivitis (VKC), it was found that nedocromil sodium 2% eyedrops produced a more rapid and marked improvement in symptoms than sodium cromoglycate 2% eyedrops and enabled lower use of steroid rescue medication. Both drugs were well tolerated and without serious side-effects. PMID- 9988436 TI - Antihistamines in severe/chronic rhinitis. AB - Oral antihistamines generally represent the first line of treatment (after allergen avoidance) in mild seasonal allergic rhinitis (SAR), and in perennial allergic rhinitis (PAR) where symptoms are intermittent. They are safe, effective and easily administered. First-generation antihistamines experienced problems mainly with sedation and anticholinergic activity. Second-generation antihistamines are safer and have largely eliminated these effects, although a very small number of patients taking terfenadine or astemizole have developed a characteristic ventricular dysrhythmia, 'torsade de pointes'. Ebastine is a potent second-generation H1-blocker that compares well with others in the class. It demonstrates no interaction with alcohol, does not induce sedation and has no clinically relevant effect on QTc interval at up to five times the maximum recommended dose. Ebastine acts rapidly to relieve symptoms of allergic rhinitis (including stuffiness) and has a long duration of action, allowing once-daily dosing. Whilst comparable in efficacy to other second-generation antihistamines at 10 mg, ebastine also has the advantage of flexible dosing. Thus, the lower dose of 10 mg is effective for treatment of mild SAR or PAR, and the dose can be increased to 20 mg once daily for control of patients with severe or chronic symptoms. PMID- 9988437 TI - Optimizing treatment options. AB - Full and accurate diagnosis of allergic rhinitis is important as a basis for treatment decisions, as many nasal disorders have similar signs and symptoms. Optimal allergen avoidance is the starting point of treatment, so causative allergens need to be identified. Oral antihistamines are effective in relieving the majority of symptoms of allergic rhinitis and allergic conjunctivitis, but provide only partial relief from nasal congestion. Topical alpha-adrenergic decongestants help to relieve congestion, but prolonged use leads to rhinitis medicamentosa. Systemic decongestants are less effective than topical agents and their use is limited by systemic and central side-effects. The value of leukotriene antagonists has yet to be fully evaluated. Intranasal ipratropium bromide helps to control watery secretions, and an aerosol may be more effective than an aqueous solution. Topical glucocorticosteroids, such as triamcinolone, are the most potent and effective agents available for treating allergic rhinitis. The available evidence indicates that there is very little systemic absorption. Sodium cromoglycate is effective in allergic rhinitis, though less so than topical steroids, and has the least adverse effects among the antiallergic agents. Immunotherapy can be effective and may be indicated in individuals who cannot avoid the causative allergen. Special considerations apply to the treatment of allergic rhinitis in elderly or pregnant patients. Finally, patients with long-standing allergic conditions should be re-assessed regularly. PMID- 9988439 TI - Genetics of complex human diseases: genome screening, association studies and fine mapping. AB - Positional cloning has been applied successfully to many Mendelian disorders. Because of the public health significance, there is strong interest in mapping susceptibility genes for common disorders, such as asthma and allergy, that have a genetic component. Genome-wide screening has been very useful in detecting regions of the genome likely to contain susceptibility genes. There are multiple chromosomal regions implicated in asthma and now the difficult process of finding the genes and relevant mutations is underway. Two approaches that are being utilized are those of association studies in candidate genes, and haplotype sharing or identical by descent (IBD) mapping. Although these are useful approaches, it is important to realize the strengths and limitations of each. The level of significance needed for an initial study or a replication study should be considered in light of the prior evidence for studying a specific gene polymorphism. Haplotype-sharing approaches, although difficult to use in outbred heterogeneous populations, may provide important insight into fine mapping and gene localization. PMID- 9988440 TI - Mapping susceptibility genes for asthma and allergy. AB - Using family data, linkage analysis has been performed to determine the location in the genome of susceptibility genes for allergy and asthma. It has now become clear that there are multiple regions of the genome that contain susceptibility genes for allergy and asthma. The results from two genome screen studies will be reviewed and compared with results from candidate gene approaches. Results from several studies show evidence for linkage to chromosomes 5, 6, 11, 12, 13 and 14 for atopy, asthma or a related phenotype such as total serum IgE levels. Many of these regions contain candidate genes involved in regulating processes that may be involved in the development or progression of allergy and asthma. Some susceptibility genes may affect the expression of these disorders while others may affect response to therapy. Susceptibility to developing allergy or asthma appears to be due to the interaction of multiple genes with the environment. PMID- 9988441 TI - Promoter polymorphisms predisposing to the development of asthma and atopy. PMID- 9988442 TI - Genetic factors in asthma severity. AB - The development of asthma in an individual depends upon the interaction of genetic factors with the environment. Asthma is a polygenic disease and both genome screening and candidate gene strategies have identified a number of putative genes that may predispose to the development of asthma. However, there are few data regarding genes that may either dictate disease severity or chronicity and genes that dictate response to treatment. Analysing asthma as a categorical variable will fail to identify genes solely involved in determining disease severity, whereas studies designed to analyse asthma as a semiquantitative trait may identify these genes in addition to disease-initiating genes. However, identifying genes specifically involved in the determination of disease severity (e.g. in airway remodelling) will be ideally performed in cohorts of asthmatics specifically recruited and using appropriate end points. This review discusses methodological issues concerned with identifying disease modifying genes in individuals with asthma, and summarizes the potential contribution of known candidate genes to the determination of disease severity. PMID- 9988443 TI - Gene by environment interactions in the development of asthma. AB - Present knowledge suggests that asthma is a heterogeneous condition. Different genetic backgrounds may or may not express themselves as asthma-like symptoms, depending on both the nature and the timing of exposures in the individual. Although particular attention has been paid to environmental factors that may increase the risk of asthma, it is equally important to understand 'protective' exposures that may have decreased during the last decades and may thus explain the reported increases in asthma prevalence. Among these 'protective' factors are certain infections and the role they may have in the inception of allergics and asthma, particularly when they occur at critical times in the development of the immune system. PMID- 9988444 TI - Environmental risk factors in childhood asthma. AB - Eighty per cent of all childhood asthma has its onset by 3 years of age. A similar percentage of childhood asthma is associated with atopy (presence of allergic rhinitis or eczema and/or positive skin prick tests). Defined risk factors for childhood asthma include allergen exposure, environmental tobacco smoke, viral respiratory illness, the presence of other atopic disease, and gender. Although a large percentage of children will have remission of asthma as they grow, they will retain the intermediate phenotypes of increased airway responsiveness and allergen and, therefore, be at risk of recrudescence of disease in adult life. PMID- 9988445 TI - Maternal programming in asthma and allergy. AB - There has been increasing interest in the possibility that the mother has an important role to play in influencing the development of fetal and infant immune responses to allergens during gestation. This finding, by several groups, of specific immune responses of infants at birth to individual trigger factors associated with an underlying immaturity of cytokine production, is intriguing in the light of the development of subsequent allergic disease. The interactions between mother, placenta and fetus are now forming a focus for ongoing research and may be a potential target for intervention aimed at preventing allergic asthma. PMID- 9988446 TI - Reciprocal age-related patterns of allergen-specific T-cell immunity in normal vs. atopic infants. AB - By adulthood there is almost universal immunological memory to aeroallergens, and the presence of allergic disease appears to be related to the nature of the underlying T-helper (Th) cell cytokine responses. The hypothesis of this study is that adult patterns of allergen specific Th-cell memory (Th-2 polarized in atopics vs. Th1 in non-atopics) can be determined in early infancy. Mononuclear cell cytokine responses to house-dust mite were measured at 6-monthly intervals from birth to 2 years of age, using ELISA (IL-10, IL-13, IFN-gamma) and sqRT/PCR (IL-4, IL-5, IL-9, IFN-gamma) in normal infants (n = 14) with no family history or allergic symptoms, and infants with a family history and definite atopy by 2 years (n = 16). Both normals and atopics showed low-level Th2 skewed allergen specific responses at birth with little accompanying IFN-gamma. The Th2 responses to house-dust mite were higher in normal newborns, who then show a rapid downregulation of these responses in the first year of life. Atopic infants instead show a consolidation of their neonatal patterns of Th2 polarized allergen specific immunity. Earlier studies indicate that neonates at high risk of atopy display diminished capacity for production of the Th1 cytokine IFN-gamma. The present study suggests for the first time that neonates who subsequently develop atopy also initially have reduced capacity to mount Th2 responses. However, in contrast to non-atopics who selectively downregulate their fetal Th2 polarized allergen-specific responses, atopic children display age-associated upregulation of Th2 immunity. PMID- 9988447 TI - The rising trends in asthma and allergic disease. AB - Considerable variation in the prevalence of childhood asthma and allergic conditions has been shown in previous studies. These differences may in part be attributable to methodological problems in defining childhood asthma and wheezing illnesses. However, the results of recent surveys using identical study instruments suggest that the variation in the distribution of the disease is real. In western societies serial prevalence studies have furthermore shown an increasing trend in the prevalence of childhood asthma and airway hyperresponsiveness. A concomitant increase in the prevalence of hay fever and atopic eczema has been reported by others. Moreover, hospitalization rates for childhood wheezing illnesses have increased in affluent countries suggesting that indeed the morbidity from these causes has increased in the last decades. Interestingly, areas of low prevalence of asthma and atopic conditions have recently been identified in developing countries and in Eastern Europe. In Eastern Germany where drastic changes towards westernization of living conditions have occurred after reunification an increase in the prevalence of hay fever and atopic sensitization has been documented over the last 4-5 years in children aged between 9 and 10 years of age. The prevalence of asthma and airway hyperresponsiveness, however, remained virtually unchanged in this age group. These children spent their first 3 years of life under socialist living conditions and were exposed to a western lifestyle only after their third birthday. Therefore, environmental factors may affect an individual's inherited susceptibility for the development of asthma and hay fever at different ages inducing changes in the prevalence of atopic diseases in populations in a time- and age-dependent way. PMID- 9988448 TI - The International Study of Asthma and Allergies in Childhood (ISAAC). ISAAC Steering Committee. AB - Despite considerable research, the aetiology of asthma and allergic disease remains poorly understood. The International Study of Asthma and Allergies In Childhood (ISAAC), was founded to maximize the value of epidemiological research into asthma and allergic disease by establishing a standardized methodology and facilitating international collaboration. It has achieved its specific aims which are to describe the prevalence and severity of asthma, rhinitis and eczema in children living in different centres and to make comparisons within and between countries; to obtain baseline measures for assessment of future trends in the prevalence and severity of these diseases; and to provide a framework for further aetiological research into genetic, lifestyle, environmental and medical care factors affecting these diseases. The ISAAC design comprises three phases. Phase One used simple core written questionnaires for two age groups, and was completed in 156 collaborating centres in 56 countries and a total of 721 601 children participated. In the 13-14 years age group 155 centres from 56 countries participated, of which 99 centres completed a video questionnaire. For the 6-7 years age group there were 91 collaborating centres in 38 countries. ISAAC Phase One has demonstrated a large variation in the prevalence of asthma symptoms in children throughout the world including hitherto unstudied populations. It is likely that environmental factors were responsible for major differences between countries. The results provide a framework for studies between populations in contrasting environments which are likely to yield new clues about the aetiology of asthma. ISAAC Phase Two will investigate possible aetiological factors, particularly those suggested by the findings of Phase One. ISAAC Phase Three will be a repetition of Phase One in the year 2000 to assess trends in prevalence. PMID- 9988449 TI - Clinical characteristics of childhood asthma. PMID- 9988450 TI - Inflammatory mechanisms in childhood asthma. AB - There is now a reasonable body of data that would suggest that the immunopathology of asthma is similar, if not identical, in childhood asthmatics compared with adult asthmatics. Indeed, we now have evidence that much of the immunopathology is established within the airways of asthmatics very early after the onset of symptoms and, given the lack of correlation with duration of symptoms, may even antedate the first manifestations. There are, however, some differences with neutrophil recruitment being somewhat more prominent than has been recorded from adult observations. The utility of any inflammation parameter in identifying the real future asthmatics has yet to be studied in sufficient detail to define sensitivity, specificity and predictive value. Such studies will be an essential prerequisite to establishing very early intervention strategies, particularly if these involve the use of inhaled and/or oral corticosteroid. PMID- 9988451 TI - Environmental allergens and childhood asthma. AB - Exposure to allergens has been shown to lead to sensitization and to the subsequent development of airway hyperresponsiveness in genetically predisposed individuals. Increasing interest is being devoted to mechanisms for the prevention of allergen sensitization and asthma development. Primary prevention (avoiding the sensitization to allergens) requires a large effort as the majority of atopic sensitizations occur in children with no demonstrable risk at the birth. Secondary prevention (deterrence of disease expression despite prior IgE sensitization) requires methods for detecting the population at risk by means of large population screening. Tertiary prevention (minimizing the morbidity for those who already have the disease) may be achieved by allergen avoidance, which has been demonstrated to effectively decrease inflammation in symptomatic patients. PMID- 9988452 TI - Evolution of asthma through childhood. AB - The greatest incidence of childhood asthma is among males under 5 years, with decreasing numbers of new cases with age. Many young children wheeze, but remission is common especially in non-atopic children without a family history of allergy or asthma, whose wheezing relates more to infections and environmental tobacco smoke exposure. The prognosis of childhood asthma is best established from population studies, in which some two-thirds of wheezy children become symptom-free as adults, whereas follow-up studies of wheezing children seen in office or specialty clinic practice, who generally have more severe asthma, show a much greater likelihood (60-80%) of persistence of asthma into adulthood. Factors predisposing to persistence of childhood asthma include a positive family history, development of atopy, environmental exposures to allergens and cigarette smoke, markers of severity of childhood asthma, and female gender. PMID- 9988453 TI - Immunoregulatory networks in asthma. AB - It is now well established that a subset of T-cell-derived cytokines (termed Th2 cytokines) programme the timing and characteristics of atopic airway disease including mast-cell sensitization, eosinophil and lymphocyte infiltration and recently mucus secretion. To date, attempts to devise ways to selectively limit the activities of Th2 cytokine-producing cells have been frustrated. However, the recent identification of the molecules which direct the activation and maturation of T cells has led to some successful attempts to block the activities of Th2 cells in models of atopic airway inflammation. Some of the agents with the most potential include antagonists of the T-cell costimulatory molecule CD28, local stimulators of the Thl subset of cytokines such as the BCG vaccine and potentially, antagonists of the eotaxin chemokine receptor and agonists of the T cell costimulatory molecule CTLA-4. Not only do such agonists and antagonists represent potential new therapies, they could represent a rich hunting ground for those who aim to determine the ways in which atopic airway disease can be diagnosed and understood. PMID- 9988454 TI - The inflammation-repair cycle in asthma: the pivotal role of the airway epithelium. PMID- 9988455 TI - The role of IgE in asthma. AB - Asthma is a multifactorial and complex disease in which allergic factors and non allergic triggers interact and result in bronchial obstruction and inflammation. Allergenic sensitization is important in the development of asthma and, although links between inhalant allergy and asthma have been known for many years, they have recently been re-emphasized. Indoor allergens are associated with asthma prevalence, severity and exacerbations whereas outdoor allergens such as pollens are associated with exacerbations. Moreover, there is a link between total IgE and asthma which appears to be independent of allergen sensitization. One of the typical aspects of airway inflammation of asthma is the infiltration of the airway wall by T helper type 2 (Th2) cells. These cells are attracted to inflammatory sites by adhesion molecules and chemokines among which CCR3 and CXCR4 receptors appear to be of importance. Differentiation of B cells into IgE secreting plasma cells is a complex cascade of events in which cytokines play a crucial role. Both IL-4 and IL-13 are inducing IgE synthesis whereas IFN-gamma and IL-12 are blocking IgE synthesis. IgE production by B cells not only requires the presence of IL-4 or IL-13, but also a physical interaction between T and B cells, involving a number of surface and adhesion molecules such as CD40-CD40L and CD28/CD80. Production of TH2-cytokines is not restricted to T cells as basophils and mast cells can produce them indicating that these cells may be of importance in the synthesis of IgE. PMID- 9988456 TI - Unique role of allergens and the epithelium in asthma. AB - The respiratory epithelium has been regarded as an inert barrier separating the human airway from the external world. Equally allergens have been perceived to be environmental proteins which interact with immunocompetent cells, activate inflammatory cells via IgE and promote the allergic response. However many allergens are biochemically active and are able to increase epithelial permeability and to stimulate epithelial cells to produce cytokines, adhesion receptors and MHC Class II expression. Thus the biochemical properties of allergens are likely to be important in enhancing the allergic responses and disease. PMID- 9988457 TI - Factors determining the severity of asthma. AB - Asthma typically can range from a disease of very mild and intermittent symptoms to one of debilitating and life-threatening disease. However, the factors that control these differences remain poorly understood. It is likely that the factors controlling the severity of asthma are many and dependent on each other. Potential factors include: (i) inflammatory; (ii) structural; (iii) hereditary/congenital; (iv) environmental; and (v) psychological/emotional; each potentially interacting and influencing the other. Finally, the question remains as to whether all asthmatics, no matter what their initial severity, potentially can develop severe disease, or whether only a certain subgroup will become severe. PMID- 9988458 TI - Corticosteroid responsiveness and the evolution of asthma. PMID- 9988459 TI - The long-term influence of therapeutic interventions in asthma with emphasis on inhaled steroids and early disease. AB - The data available to show the long-term benefits of any pharmacological interventions in asthma is scanty. Usually the beneficial effects disappear gradually when the treatment is withdrawn. The evidence showing that treatment with drugs could change the natural course of asthma is largely lacking. Only a few controlled studies have lasted more than 1 year, while asthma can be a disease for life. Nevertheless, the short-term benefits of treatment with inhaled steroids justify their introduction as soon as the diagnosis of asthma is established. Regular use of inhaled steroids especially during the early stages of asthma often makes it a less troublesome disease. Regular use of long-acting beta2-agonists is useful in preventing exacerbations in persistent asthma, but their influence on the long-term outcome is quite unknown. Exploration of the possible disease outcome modifying effect of new innovations such as leukotriene antagonists should be put in the clinical study programmes. In future, the combination of immunological and pharmacological treatments may offer the key for more permanent results in asthma therapy. PMID- 9988460 TI - Lipid mediator pathways in the lung: leukotrienes as a new target for the treatment of asthma. AB - This article summarizes recent evidence supporting that antileukotriene drugs represent a new treatment of asthma which may be particularly effective when combined with drugs that have complementary effects on airway obstruction and inflammation. Firstly, it has been documented that glucocorticosteroids do not inhibit in vivo production of leukotrienes in asthmatics. In line with such findings, addition of antileukotriene drugs to a group of aspirin-intolerant asthmatics maintained on conventional therapy was found to result in an improvement of the asthma over and above the effect of the baseline treatment with inhaled and/or oral glucocorticosteroids. Likewise, in a 6-week trial in a group of severe asthmatics, the asthma deterioration caused by a reduction of the dose of inhaled steroids by half, was prevented by addition of a leukotriene antagonist to the lowered dose of glucocorticosteroids. Current evidence therefore supports that antileukotriene drugs treat components of the pathophysiology which are left unaffected by treatment with glucocorticosteroid. Secondly, in experimental studies as well as in a recent allergen bronchoprovocation study in asthmatics, it has been found that the combination of antihistaminics with antileukotriene drugs will result in a profound inhibition of both the early and the late phase of allergen-induced airway obstruction. It is hypothesized that such a combination may be useful against bronchoconstriction induced by other asthma trigger factors as well as in the treatment of asthma and rhinitits. PMID- 9988461 TI - Leukotriene modifiers as novel therapeutics in asthma. AB - After years of research, the components of slow-reacting substance of anaphylaxis have been identified as the cysteinyl leukotrienes C4, D4, and E4. Leukotrienes are now known to be important mediators of chronic asthma. Leukotrienes cause bronchoconstriction, oedema, and mucus secretion in models of asthma and are produced in excess quantities in asthmatic patients. Leukotriene receptor antagonists and biosynthesis inhibitors have been produced to improve the signs and symptoms of asthma. These agents block laboratory challenges simulating chronic asthma such as exercise, allergen, and aspirin challenge. They also are effective in studies of chronic asthma in a wide variety of patient types demonstrating that leukotrienes are indeed important mediators of asthma. Over the next several years the appropriate place in asthma therapy for these new agents will be defined. PMID- 9988462 TI - The prospects for long-term intervention in asthma with antileukotrienes. AB - The antileukotriene drugs are the first new therapeutic agents approved for the treatment of asthma in more than 20 years. The currently available compounds are orally active and either prevent the cysteinyl leukotrienes from binding to and activating the cysLT-1 receptor in the lung (leukotriene receptor antagonists, LTRAs) or inhibit leukotriene synthesis (leukotriene synthesis inhibitors, LTSIs). The antileukotrienes acutely bronchodilate the airways of patients with baseline bronchoconstriction, although usually not as well as beta-agonists. When used regularly they produce rapid improvements of pulmonary function and symptoms in patients with mild-to-moderate asthma, and probably of those with more severe asthma as well, which persists for the duration of treatment. Yet, individual responses to the antileukotrienes are variable and not predictable based on clinical criteria. Recent studies suggest they reduce asthmatic airway inflammation. The few comparator studies with other asthma medications indicate they are equal or more effective than cromolyn but equal or less effective than low-to-moderate doses of inhaled corticosteroids. Initial experience with the antileukotrienes reveals limited toxicity and a favourable therapeutic-to-toxic ratio. The exact role of the antileukotrienes in the treatment of asthma remains to be determined, as does the relative potency of the various agents. PMID- 9988463 TI - Pharmacogenetics of the 5-lipoxygenase pathway in asthma. AB - It is now well appreciated that asthma is a chronic inflammatory disease of the airways; among the inflammatory cells that have been implicated in the asthmatic lesion are eosinophils and mast cells. Although these cells have the capacity to produce a number of distinct chemical mediators, the cysteinyl leukotrienes have recently been identified as important mediators of the asthmatic response. The leukotrienes are derived from arachidonic acid released from membrane phospholipids by the action of phospholipases. The archidonic acid so released in the presence of the 5-lipoxygenase (5-LO) activating protein becomes a substrate for the enzyme 5-LO. This enzyme catalyses the stereo-specific addition of molecular oxygen to arachidonic acid to form the product known as leukotriene A4. Leukotriene A4 subsequently becomes a substrate for one of two enzymes, leukotriene A4 epoxide hydrolase or LTC4 synthase. The former catalyses the formation of LTB4 while the later catalyses the formation of the cysteinyl leukotrienes. Thus the enzyme 5-LO is critically posed to serve as a regulator of leukotriene synthesis. 5-LO action is known to be regulated at a number of levels; the mechanisms include regulation of action of the mature protein and regulation of 5-LO gene transcription and translation; there is good reason to believe that all forms of 5-LO regulation are highly interdependent. In this regard we describe the presence and functional consequences of a series of naturally occurring mutations in 5-LO core promoter. These mutations modify gene transcription in vitro, and may have functional consequences in vivo. PMID- 9988464 TI - What can we learn from late-onset and occupational asthma? AB - Late-onset asthma and occupational asthma may provide interesting models of human asthma to compare with the most frequent type of atopic early-onset asthma. The discovery of similarities and discrepancies in the aetiology and pathogenesis of these different diseases might provide new insights on different mechanisms producing the same phenotype and, thus, by recognizing the different underlying mechanisms of the different forms of asthma, may allow better targeting of prevention and treatment. Occupational asthma, in addition to being a late-onset asthma, provides the unique opportunity to study the development of asthma under measurable exposure conditions, and consequently to examine the effect of cessation of exposure which, at variance with allergen avoidance, is possible in most of the cases. PMID- 9988465 TI - Mechanisms of asthma exacerbation. PMID- 9988466 TI - Are chronic obstructive pulmonary disease (COPD) and asthma different diseases? AB - In the past it has been hypothesized that asthma and chronic obstructive pulmonary disease (COPD) are related diseases. As both show high prevalences and as smoking may occur in both groups of patients the simultaneous presence of both diseases in the same subject may well occur. The most characteristic features of asthma are short-term changes in airway caliber, reversible airflow limitation, bronchial hyperresponsiveness as well as eosinophilic and lymphocytic airway inflammation. The common definition of COPD implies long-term changes in airway calibre, less or irreversible airflow obstruction, no or less common bronchial hyperresponsiveness and neutrophilic airway inflammation. By analysing the results of epidemiology, risk factors, airway morphology, lung function and markers of airway inflammation in both diseases, it becomes clear that asthma and COPD share some similarities. However, their pathological presentations differ considerably and this provides evidence that the two syndromes are, in fact, different diseases. Furthermore, the analysis of data on lung volumes, diffusion capacity and aerosol-derived airway morphology shows important differences between asthma and COPD. It is suggested that the specific type of airway inflammation in both diseases is responsible for the peculiar pattern of lung function abnormalities. PMID- 9988467 TI - Asthma in older people. AB - From the clinical perspective, asthma in the older patient may be difficult to diagnose because of the non-specificity of presentation and the wide range of differential diagnoses. Prior to confirmation of asthma in the older patient, both respiratory and cardiac investigation may be necessary. Polypharmacy is inherent in treating older people and accurate drug histories are essential in order to identify patients with drug-induced bronchospasm and avoid interactions with asthma medication. Patient and carer education is vital, and a structured approach to follow-up which includes measurement of lung function and assessment of inhaler technique should be carried out in every asthmatic regardless of age. Finally, there is a great need for health services and those in the commercial sector that are involved in asthma care to ensure that future research and development rises to the challenge of an ageing population. PMID- 9988468 TI - SOS and Mayday: multiple inducible mutagenic pathways in Escherichia coli. AB - Environmental and physiological stress conditions can transiently alter the fidelity of DNA replication. The DNA damage-mediated SOS response in Escherichia coli is the best-known example of such an 'inducible mutagenesis' or 'transient mutator' pathway. Emerging evidence suggests the existence of a number of other stress-inducible pathways that also affect the fidelity of replication. Among the more provocative recent findings are UVM, an SOS-independent damage-inducible mutagenic pathway, and a new recA-dependent but umuD/C-independent pathway that appears to be provoked by translational stress. These findings alter our view of inducible mutagenesis, and anticipate the existence of previously unrecognized links between protein synthesis and DNA replication. PMID- 9988469 TI - Enteropathogenic and enterohaemorrhagic Escherichia coli: more subversive elements. AB - Enteropathogenic (EPEC) and enterohaemorrhagic Escherichia coli (EHEC) constitute a significant risk to human health worldwide. Both pathogens colonize the intestinal mucosa and, by subverting intestinal epithelial cell function, produce a characteristic histopathological feature known as the 'attaching and effacing' (A/E) lesion. Although EPEC was the first E. coli to be associated with human disease in the 1940s and 1950s, it was not until the late 1980s and early 1990s that the mechanisms and bacterial gene products used to induce this complex brush border membrane lesion and diarrhoeal disease started to be unravelled. During the past few months, there has been a burst of new data that have revolutionized some basic concepts of the molecular basis of bacterial pathogenesis in general and EPEC pathogenesis in particular. Major breakthroughs and developments in the genetic basis of A/E lesion formation, signal transduction, protein translocation, host cell receptors and intestinal colonization are highlighted in this review. PMID- 9988470 TI - Bacillus subtilis tetA(L) gene expression: evidence for regulation by translational reinitiation. AB - The tetA(L) gene of Bacillus subtilis encodes a transmembrane protein that can function as a Tc-metal/H+ antiporter, conferring low-level resistance to tetracycline. The TetA(L) coding sequence is preceded by a leader region that contains a 20-amino-acid open reading frame and an appropriately spaced ribosome binding site. Expression of the gene is induced by addition of tetracycline, which is thought to act by binding to ribosomes that translate the tetA(L) leader peptide coding sequence. Here we demonstrate that induction of tetA(L) expression includes minor transcriptional and major translational components. Deletion and point mutations of the tetA(L) leader region were constructed to probe the mechanism of translational induction. To account for the observed mutant phenotypes, we propose that tetA(L) expression is regulated by a translational reinitiation mechanism. PMID- 9988471 TI - Cellular function of elastase in Pseudomonas aeruginosa: role in the cleavage of nucleoside diphosphate kinase and in alginate synthesis. AB - Elastase is a major virulence factor in Pseudomonas aeruginosa that is believed to cause extensive tissue damage during infection in the human host. Elastase is secreted in non-mucoid P. aeruginosa. It is known that secretion of most virulence factors such as elastase, lipase, exotoxin A, etc., in P. aeruginosa is greatly reduced in alginate-secreting mucoid cells isolated from the lungs of cystic fibrosis (CF) patients. We have previously reported that in mucoid P. aeruginosa, an intracellular protease cleaves the 16 kDa form of nucleoside diphosphate kinase (Ndk) to a truncated 12 kDa form. This smaller form is membrane associated and has been observed to form complexes with specific proteins to predominantly generate GTP, an important molecule in alginate synthesis. The main aim of this study was to purify and characterize this protease. The protease was purified by hydrophobic interaction chromatography of the crude extract of mucoid P. aeruginosa 8821, a CF isolate. Further analysis using a gelatin containing SDS-polyacrylamide gel detected the presence of a 103 kDa protease, which when boiled, migrated as a 33 kDa protein on a SDS polyacrylamide gel. The first 10 amino acids from the N-terminus of the 33 kDa protease showed 100% identity to the mature form of elastase. An elastase negative lasB::Cm knock-out mutant in the mucoid 8821 background was constructed, and it showed a non-mucoid phenotype. This mutant showed the presence of only the 16 kDa form of Ndk both in the cytoplasm and membrane fractions. We present evidence for the retention of active elastase in the periplasm of mucoid P. aeruginosa and its role in the generation of the 12 kDa form of Ndk. Finally, we demonstrate that elastase, when overproduced in both mucoid and non-mucoid cells, stimulates alginate synthesis. This suggests that the genetic rearrangements that trigger mucoidy in P. aeruginosa also allow retention of elastase in the periplasm in an active oligomeric form that facilitates cleavage of 16 kDa Ndk to its 12 kDa form for the generation of GTP, required for alginate synthesis. PMID- 9988472 TI - Pho signal transduction network reveals direct transcriptional regulation of one two-component system by another two-component regulator: Bacillus subtilis PhoP directly regulates production of ResD. AB - The Bacillus subtilis ResD-ResE two-component system is responsible for the regulation of a number of genes involved in cytochrome c biogenesis and haem A biosynthesis, and it is required for anaerobic respiration in this organism. We reported previously that the operon encoding these regulatory proteins, the resABCDE operon, is induced under several conditions, one of which is phosphate starvation. We report here that this transcription requires the PhoP-PhoR two component system, whereas other induction conditions do not. The PhoPP response regulator directly binds to and is essential for transcriptional activation of the resABCDE operon as well as being involved in repression of the internal resDE promoter during phosphate-limited growth. The concentration of ResD in various phoP mutant strains corroborates the role of PhoP in the production of ResD. These interactions result in a regulatory network that ties together the cellular functions of respiration/energy production and phosphate starvation. Significantly, this represents the first evidence for direct involvement of one two-component system in transcription of a second two-component system. PMID- 9988473 TI - Identification of a co-repressor binding site in catabolite control protein CcpA. AB - The catabolite control protein CcpA is the central regulator of carbon catabolite repression in Bacilli and other Gram-positive bacteria. A comparison of 12 CcpA like sequences with regulators from the LacI/GalR family defines a CcpA subfamily based on extensive similarities found among CcpAs and not in 32 other members of the family. These amino acids are clustered in three blocks in the CcpA sequence. Their interpretation, assuming a PurR-like fold, reveals that almost all of them are surface exposed and form a continuous patch on the N-terminal subdomain of the protein core extending into the DNA reading head. We introduced nine single amino acid exchanges in the subfamily specific residues of CcpA from Bacillus megaterium. Six mutants, namely CcpA47RS, 79AE, 89YE, 295YR, 299YE and 303RD, are inactive or severely impaired in catabolite repression, underlining their relevance for CcpA function. They are negatively transdominant over wild-type CcpA demonstrating their ability to correctly fold for dimerization. Five of them are unable or impaired in binding HPr-Ser-46-P in vitro, establishing a correlation between catabolite repression efficiency and HPr-Ser-46-P binding. These results support the hypothesis that the conserved region in CcpA is the HPr Ser-46-P binding site. PMID- 9988474 TI - The high-pathogenicity island of Yersinia pseudotuberculosis can be inserted into any of the three chromosomal asn tRNA genes. AB - Pathogenicity islands (PAIs) have been identified in several bacterial species. A PAI called high-pathogenicity island (HPI) and carrying genes involved in iron acquisition (yersiniabactin system) has been previously identified in Yersinia enterocolitica and Yersinia pestis. In this study, the HPI of the third species of Yersinia pathogenic for humans, Y. pseudotuberculosis, has been characterized. We demonstrate that the HPI of strain IP32637 has a physical and genetic map identical to that of Y. pestis. A gene homologous to the bacteriophage P4 integrase gene is located downstream of the asn tRNA locus that borders the HPI of strain IP32637. This int gene is at the same position on the HPI of all three pathogenic Yersinia species. However, in contrast to Y. pestis 6/69, the HPI of Y. pseudotuberculosis IP32637 is not invariably adjacent to the pigmentation segment and can be inserted at a distance > or = 190 kb from this segment. Also, in contrast to Y. pestis and Y. enterocolitica, the HPI of Y. pseudotuberculosis IP32637 can precisely excise from the chromosome, and, strikingly, it can be found inserted in any of the three asn tRNA loci present on the chromosome of this species, one of which is adjacent to the pigmentation segment. The pigmentation segment, which is present in Y. pestis but not in Y. enterocolitica, is also present and well conserved in all strains of Y. pseudotuberculosis studied. In contrast, the presence and size of the HPIs vary depending on the serotype of the strain: an entire HPI is found in strains of serotypes I only, a HPI with a 9 kb truncation in its left-hand part that carries the IS100 sequence and the psn and ybtE genes characterizes the strains of serotype III, and no HPI is found in strains of serotypes II, IV and V. PMID- 9988475 TI - Differentiation-associated surface antigen variation in the ancient eukaryote Giardia lamblia. AB - Encystation of Giardia lamblia is required for survival outside the host, whereas excystation initiates infection. The dormant cyst was considered an adaptation to external survival and passage through the stomach. However, we found previously that trophozoites which had recovered after completion of the life cycle had switched their major variant surface protein (VSP), called TSA 417, but neither the timing nor the molecular mechanism of switching had been elucidated. Here we demonstrate that TSA 417 predominates in cysts, but is downregulated during the stage of excystation that models cyst arrival in the small intestine. Transcripts of new VSPs appear late in encystation, and during and after excystation. Trophozoites appear to prepare for switching during encystation, when the major VSP on the cell surface diminishes and is internalized in lysosome-like vacuoles. As short-range DNA rearrangements were not detected, giardial VSP switching during differentiation appears to resemble the in situ switching of surface glycoproteins in African trypanosomes. We also report a unique extended 15 nucleotide polyadenylation signal in all VSP transcripts, but not in other known giardial genes. Antigenic variation during encystation-excystation may be a novel form of immune evasion that could help explain the common occurrence of reinfection by Giardia and other parasites with similar life cycles. PMID- 9988476 TI - SarA level is a determinant of agr activation in Staphylococcus aureus. AB - The control of virulence determinant expression in Staphylococcus aureus is a complex process involving global regulatory loci such as sar and agr. The sar locus consists of a 372 bp sarA open reading frame (ORF) preceded by a triple promoter region interspersed with two putative smaller ORFs (ORF3 and ORF4). The triple promoter system yields three overlapping sar transcripts (sarA, sarC and sarB of 0.56, 0.8 and 1.2 kb respectively). We have recently shown that the SarA protein binds to the agr promoter region to stimulate the transcription of RNAII and RNAIII, two major transcripts encoded within the agr locus. To assess the role of the region upstream of sarA in agr expression, we evaluated the contribution of ORF3 and ORF4 to SarA protein expression and to agr activation by introducing nonsense mutations into the respective ORFs. Northern analysis of sar mutant clones containing these mutations carried on a shuttle plasmid revealed that all three sar-related transcripts are present. Using anti-SarA monoclonal antibodies with defined epitopes in a competitive ELISA to determine the SarA protein level, we found that the introduction of a stop codon in ORF3 on a shuttle plasmid carrying the intact sar locus in a sar mutant led to a significant decrease in SarA protein level compared with the non-mutated control. The effect of a nonsense mutation in ORF4 on SarA levels is much less. Likewise, an analogous sar mutant clone with a deletion in ORF3 also displayed a lower SarA level than its intact counterpart. The reduction in SarA expression correlated with a lower level of agr activation in the corresponding sar mutant clone. These data suggest that ORF3, and to a lesser degree ORF4, may affect agr expression by modulating SarA protein expression. PMID- 9988477 TI - Identification of a 47 kDa fibronectin-binding protein expressed by Borrelia burgdorferi isolate B31. AB - The attachment of pathogenic microorganisms to host cells and tissues is often mediated through the expression of surface receptors recognizing components of the extracellular matrix (ECM). Here, we investigate the ability of Borrelia spirochaetes to bind the ECM constituent, fibronectin. Borrelia lysates were separated by SDS-PAGE, transferred to nitrocellulose and probed with alkaline phosphatase-labelled fibronectin (fibronectin-AP). Five of six Borrelia species and four of eight B. burgdorferi sensu lato isolates expressed one or more fibronectin-binding proteins. Borrelia burgdorferi isolate B31 expressed a 47 kDa (P47) fibronectin-binding protein that was localized to the outer envelope based on susceptibility to proteinase K. The interaction of P47 with fibronectin was specific, and the region of fibronectin bound by P47 mapped to the gelatin/collagen binding domain. P47 was purified by affinity chromatography, digested with endoproteinase Lys-C, and the peptide fragments analysed by liquid chromatography/tandem mass spectroscopy. A search of protein databases disclosed that the P47 peptide mass profile matched that predicted for the bbk32 gene product of B. burgdorferi isolate B31. The bbk32 gene was cloned into Escherichia coli, and the ability of recombinant BBK32 to bind fibronectin and inhibit the attachment of B. burgdorferi was demonstrated. The identification of BBK32 as a receptor for fibronectin binding may enhance our understanding of the pathogenesis and chronic nature of Lyme disease. PMID- 9988478 TI - Cytosolic enzymes with a mitochondrial ancestry from the anaerobic chytrid Piromyces sp. E2. AB - The anaerobic chytrid Piromyces sp. E2 lacks mitochondria, but contains hydrogen producing organelles, the hydrogenosomes. We are interested in how the adaptation to anaerobiosis influenced enzyme compartmentalization in this organism. Random sequencing of a cDNA library from Piromyces sp. E2 resulted in the isolation of cDNAs encoding malate dehydrogenase, aconitase and acetohydroxyacid reductoisomerase. Phylogenetic analysis of the deduced amino acid sequences revealed that they are closely related to their mitochondrial homologues from aerobic eukaryotes. However, the deduced sequences lack N-terminal extensions, which function as mitochondrial leader sequences in the corresponding mitochondrial enzymes from aerobic eukaryotes. Subcellular fractionation and enzyme assays confirmed that the corresponding enzymes are located in the cytosol. As anaerobic chytrids evolved from aerobic, mitochondria-bearing ancestors, we suggest that, in the course of the adaptation from an aerobic to an anaerobic lifestyle, mitochondrial enzymes were retargeted to the cytosol with the concomitant loss of their N-terminal leader sequences. PMID- 9988479 TI - The type III secretion determinants of the flagellar anti-transcription factor, FlgM, extend from the amino-terminus into the anti-sigma28 domain. AB - The flagellar-specific anti-sigma factor, FIgM, inhibits the expression of late flagellar genes until the hook-basal body structure is assembled and competent for export of the flagellins and hook-associated proteins (flagellar late proteins). FIgM monitors this assembly checkpoint by being a substrate for export via the hook-basal body structure, which includes a type III protein secretion complex. Amino acid sequence alignment of late-secreted flagellar proteins identified a region of homology present in the amino-terminus of FIgM and the other late flagellar proteins, but not in flagellar proteins secreted earlier during flagellar biosynthesis. Single amino acid substitutions at specific positions within this motif decreased the export of FIgM. Deletion of this region (S3-P11) resulted in lower intracellular FIgM levels, but did not prevent recognition and export by the flagellar-specific secretion system. Mutations were isolated in a second region of FIgM spanning residues K27 to A65 that exhibited increased anti-sigma28 activity. These FIgM 'hyperinhibitor' mutants were secreted less than wild-type FIgM. Mutations that interfere with the secretion of FIgM without abolishing anti-sigma28 activity have a negative effect upon the secretion of a His-tagged FIgM mutant that lacks anti-sigma28 activity. Models are proposed to explain the dominant negative phenotype of the FIgM secretion mutants reported in this study. PMID- 9988480 TI - The E protein of satellite phage P4 acts as an anti-repressor by binding to the C protein of helper phage P2. AB - Temperate phage P2 has the capacity to function as a helper for the defective, unrelated, satellite phage P4. In the absence of a helper, P4 can either lysogenize its host or establish itself as a plasmid. For lytic growth, P4 requires the structural genes, packaging and lysis functions of the helper. P4 can get access to the late genes of prophage P2 by derepression, which is mediated by the P4 E protein. E has been hypothesized to function as an anti repressor. To locate possible epitopes interacting with E, an epitope display library was screened against E, and the most frequent sequence found had some identities to a region within P2 C. Using the yeast two-hybrid system, a clear activation of a reporter gene was found, strongly supporting an interaction between E and C. The P2 C repressor is believed to act as a dimer, which is confirmed in this work using in vivo dimerization studies. The E protein was also found to form dimers in vivo. The E protein only affects dimerization of C marginally, but the presence of E enhances multimeric forms of C. Furthermore, binding of the C protein to its operator is inhibited by E in vitro, indicating that the anti-repressor function of E is mediated by the formation of multimeric complexes of E and C that interfere with the binding of C to its operator. PMID- 9988481 TI - Targeting of the Yersinia pestis YopM protein into HeLa cells and intracellular trafficking to the nucleus. AB - The YopM virulence protein of Yersinia pestis has been described as binding human alpha-thrombin and inhibiting thrombin-induced platelet aggregation in vitro. However, recent studies have shown that a YopM-CyaA fusion protein could be targeted vectorially into eukaryotic cells through the Yersinia type III secretion system. In this study, our objective was to characterize YopM's fate in more detail. We followed YopM in the culture medium and inside infected HeLa cells. We confirmed that the native YopM is targeted into HeLa cells, where it is insensitive to exogenous trypsin. The bacteria must be surface located to target YopM, and YopB and YopD are necessary, whereas the LcrE protein (called also YopN) makes this process more efficient. Immunofluorescence localization revealed that YopM, in contrast to YopE, is not only targeted to the cytoplasm but also trafficks to the cell's nucleus by means of a vesicle-associated pathway that is strongly inhibited by brefeldin A, perturbed by monensin or bafilomycin A1 and dependent upon microtubules (decreased by colchicine and nocodazole). These findings revealed a novel interaction of Yersinia pestis with its eukaryotic host. PMID- 9988482 TI - Conversion to bidirectional replication after unidirectional initiation from R1 plasmid origin integrated at oriC in Escherichia coli. AB - The cell division phenotypes of Escherichia coli with its chromosome replication driven by oriR (from plasmid R1) were examined by fluorescence microscopy and flow cytometry. Chromosome replication patterns in these strains were followed by marker frequency analyses. In one of the strains, the unidirectional oriR was integrated so that the replication fork moved clockwise from the oriC region, and bacterial growth and division were similar to those of the wild-type parent. The bacteria were able to convert the unidirectional initiation from oriR into bidirectional replication. The site for conversion of uni- to bidirectional replication seemed to be localized and could be mapped genetically within 6 min to the immediate right of the minimal oriC. Replication starting in the counterclockwise direction from the R1 replicon integrated at the same site in the opposite orientation could not be described as either bi- or unidirectional, as no single predominant origin could be discerned from the more or less flat marker frequency pattern. These strains also showed extensive filamentation, irregular nucleoid distribution and the presence of anucleate cells, indicative of segregation and division defects. Comparison among intR1 derivatives differing in the position of the integrated oriR relative to the chromosome origin suggested that the oriC sequence itself was dispensable for the conversion to bidirectionality. However, passage of the replication fork over the 6 min region to the right of oriC seemed important for the bidirectional replication pattern and normal cell division phenotype. PMID- 9988483 TI - The type II O-antigenic polysaccharide moiety of Burkholderia pseudomallei lipopolysaccharide is required for serum resistance and virulence. AB - Melioidosis, an infection caused by the gram-negative bacterial pathogen Burkholderia pseudomallei, is endemic in south-east Asia and northern Australia. Acute septicaemic melioidosis is a major cause of morbidity and mortality, especially in north-east Thailand. B. pseudomallei is highly resistant to the bactericidal activity of normal human serum (NHS), and we have found that B. pseudomallei 1026b multiplies in 10-30% NHS. We developed a simple screen for the identification of serum-sensitive mutants based on this novel phenotype. Approximately 1200 Tn5-OT182 mutants were screened, and three serum-sensitive mutants were identified. The type II O-antigenic polysaccharide (O-PS) moiety of lipopolysaccharide was not present in the serum-sensitive mutants. A representative serum-sensitive mutant, SRM117, was killed by the alternative pathway of complement and was less virulent than 1026b in three animal models of melioidosis. The Tn5-OT182 integrations in the serum-sensitive mutants were physically linked on the B. pseudomallei chromosome, and further genetic analysis of this locus revealed a cluster of 15 genes required for type II O-PS production. The proteins encoded by these genes were similar to proteins involved in bacterial polysaccharide biosynthesis. The results presented here demonstrate that type II O-PS is essential for B. pseudomallei serum resistance and virulence. PMID- 9988484 TI - Nitrogen control of the glnN gene that codes for GS type III, the only glutamine synthetase in the cyanobacterium Pseudanabaena sp. PCC 6903. AB - Pseudanabaena sp. strain PCC 6903 is the first cyanobacteria lacking the typical prokaryotic glutamine synthetase type I encoded by the glnA gene. The glnN gene product, glutamine synthetase type III, is the only glutamine synthetase activity present in this cyanobacterium. Analysis of glnN expression clearly indicated a nitrogen-dependent regulation. Pseudanabaena glnN gene expression and GSIII activity were upregulated under nitrogen starvation or using nitrate as a nitrogen source, while low levels of transcript and activity were found in ammonium-containing medium. Primer extension analysis showed that the glnN gene promoter structure resembled that of the NtcA-related promoters. Mobility shift assays demonstrated that Synechocystis sp. PCC 6803 NtcA protein, expressed and purified from Escherichia coli, bound to the promoter of the Pseudanabaena 6903 glnN gene. The NtcA control of the glnN gene in this cyanobacterium suggested that, in the absence of a glnA gene, NtcA took control of the only glutamine synthetase gene in a fashion similar to the way the glnA gene is governed in those cyanobacteria harbouring a glnA gene. PMID- 9988485 TI - Promoter element spacing controls basal expression and light inducibility of the cyanobacterial secA gene. AB - The Synechocystis PCC6803 secA gene was found to be essential for cell viability and to be transcriptionally controlled by the redox state of the cells. The basic promoter (BP, -71 to +47 relative to the transcription start site) is controlled by three cis-acting elements, which together mediate the fourfold light induction of BP activity. The positively acting element (PE1, -361 to -71) upstream of BP exerts a twofold stimulation of BP; the negative element (NE, +47 to +104) downstream of BP decreases BP strength about sixfold. The PE2 element (+104 to +175) lying in the coding sequence overcomes NE-dependent downregulation of BP. BP harbours Escherichia coli sigma70-like promoter elements -35 (5'-TTGAat-3') and -10 (5'-TAagAT-3'). The -10 motif, which has the features of an 'extended 10' box, is absolutely essential to promoter activity. The -35 hexamer is critical to the enhancement of promoter strength above BP level and to light inducibility, both features involving regulatory elements flanking BP. Most interestingly, reducing the length of the 30 bp spacing between the -35 and -10 boxes down to 17 bp was found to increase promoter activity and to confer light inducibility to BP. This demonstrates that promoter element spacing controls basal expression and light inducibility of the secA gene. PMID- 9988486 TI - A new set of chemotaxis homologues is essential for Myxococcus xanthus social motility. AB - Myxococcus xanthus cells aggregate and develop into multicellular fruiting bodies in response to starvation. A new M. xanthus locus, designated diffor defective in fruiting, was identified by the characterization of a mutant defective in fruiting body formation. Molecular cloning, DNA sequencing and sequence analysis indicate that the dif locus encodes a new set of chemotaxis homologues of the bacterial chemotaxis proteins MCPs (methyl-accepting chemotaxis proteins), CheW, CheY and CheA. The dif genes are distinct genetically and functionally from the previously identified M. xanthus frz chemotaxis genes, suggesting that multiple chemotaxis-like systems are required for the developmental process of M. xanthus fruiting body formation. Genetic analysis and phenotypical characterization indicate that the M. xanthus dif locus is required for social (S) motility. This is the first report of a M. xanthus chemotaxis-like signal transduction pathway that could regulate or co-ordinate the movement of M. xanthus cells to bring about S motility. PMID- 9988487 TI - Italian contributions to the history of general and medical mycology. AB - Important contributions by Italian mycologists that guided the field of medical mycology are discussed. Much of our current taxonomy resulted from their contributions. PMID- 9988488 TI - The role of immunoreconstitution in the management of refractory opportunistic fungal infections. AB - Systemic fungal infections are an increasingly important threat to immunocompromised patients. In particular, invasive disease due to Candida spp., Aspergillus spp. and other moulds is associated with high mortality rates in these patients, despite the many recent advances in antifungal chemotherapy. Recent studies examining the immunopathogenesis of these infections have provided increased insights into the relative importance of the different compartments of host immune defences for these fungi. In parallel, a number of cytokines have been discovered and studies of their involvement in antifungal host defences both in vitro and in experimental animal models of fungal infections have become possible. Due to their ability to upregulate phagocyte number and/or function, the cytokines of greatest interest are granulocyte colony-stimulating factor, granulocyte-macrophage colony-stimulating factor, macrophage colony-stimulating factor, interferon-gamma, interleukin-1 and tumour necrosis factor-alpha. Adjuvant use of these cytokines may be of value for some refractory fungal infections, as may reconstitution of immune response by transfusion of allogeneic phagocytes. Further evaluation of the safety and efficacy of these modalities of immunotherapy is a new and promising area for research. PMID- 9988489 TI - Nocardia, nocardiosis and mycetoma. AB - The recent emergence of invasive infections due to Nocardia spp., including nosocomial outbreak, is now evident. Newer molecular diagnostic and typing methods are developed. Although sulfonamide-based therapy is generally effective, optimal treatment may be guided by antimicrobial susceptibility testing of isolates. The improved classification of nocardiae and other related genera such as actinomadurae, using the 16S ribosomal RNA sequencing, provide a sound basis for improved diagnostic methods for the identification of members of clinically significant species. The commonest cause of eumycetoma in Sudan is Madurella mycetomatis, and Streptomyces somaliensis and Actinomadura madurae for actinomycetoma. The humoral immunity response in actinomycetoma patients and in experimental mice was measured and significant titre of anti-P24 antibody was demonstrated. PMID- 9988490 TI - Fate of transforming DNA in pathogenic fungi. AB - Genetic engineering is an important tool in helping us to define the molecular basis of pathogenicity and is also useful in helping us to identify new therapeutic targets in pathogenic fungi. Molecular genetic manipulation of micro organisms requires the development of plasmid-mediated transformation systems that include: (i) infusion of exogenous DNA into recipient cells, (ii) expression of genes present on the incoming DNA, and (iii) stable maintenance and replication of the inserted DNA leading to expression of the desired phenotypic trait. Transformation systems have been developed for only a handful of fungi that are pathogenic to humans including several species of Candida, Cryptococcus neoformans, Histoplasma capsulatum, Blastomyces derrmatitidis, Aspergillus fumigatus, Wangiella dermatitidis (Exophiala dermatitidis) and Coccidioides immitis. Except for Candida species and A. fumigatus, where passage of exogenous DNA into recipient cells has been achieved readily using methods developed for transformation of Saccharomyces cerevisiae and Aspergillus nidulans, respectively, development of transformation systems in other pathogenic fungi has been delayed considerably and has only been possible recently with the introduction of electroporation and biolistic methods. Conventional spheroplasting methods or cell wall permeabilization methods using lithium acetate have not been successful for transformation of C. neoformans and work with only low efficiency in H. capsulatum. The fate of incoming DNA varies greatly in these pathogenic species regardless of their phylogenetic relationships. Understanding the fate of incoming DNA is critical for the construction of transforming vectors and the molecular manipulation of the organisms. In this symposium, recent advances in molecular genetic systems including transformation systems, the fate of incoming DNA and strategies for targeted integration are discussed in relation to four pathogenic fungi. PMID- 9988491 TI - Stress proteins in fungal diseases. AB - Heat shock proteins (hsps) are ubiquitous families of proteins, found in all organisms studied so far. They are highly conserved across the species barrier and serve fundamental functions in cell physiology. The term 'heat shock' was adopted because of the early observation of the heat-inducible nature of these proteins, although, as it is now realized that they can be induced by a variety of stressful stimuli, it is probably more appropriate to call them 'stress proteins'. The nomenclature of many hsps, for example hsp90, hsp70 and hsp60, reflects the approximate molecular mass of hsps within each of these families. For many bacterial and parasitic infections, hsps were first recognized as immunodominant antigens on immunoblots of extracts from the organism probed with immune sera, or in T-cell proliferation assays. They have now been identified in a range of fungal pathogens, again often linked to an immune response. In this symposium, we review the association of hsps with humoral immunity to candidosis and aspergillosis, cellular immunity to histoplasmosis, and the identification of hsp70 in another dimorphic fungus, Paracoccidioides brasiliensis. Finally, the crucial role of the membrane in setting the temperature of the heat shock response in yeasts is discussed. PMID- 9988492 TI - Molecular phylogeny and taxonomy of medically important fungi. AB - Some recent advances in study of molecular evolution and taxonomy of human pathogens are discussed. In systemic Onygenales as well as in Chaetothyriales, pathogenic species are phylogenetically intermingled with non-pathogenic taxa. When a teleomorph of Coccidioides immitis is eventually found, it is predicted to resemble Uncinocarpus, a genus otherwise comprising environmental species. In the dermatophytes, Trichophyton and Microsporum are paraphyletic, whereas Epidermophyton is polyphyletic. On the basis of 18S and ITS rDNA sequencing data, Exophiala anamorphs (black yeasts) are confirmed to be closely related to the ascomycete genus Capronia. The related neurotropic species Cladophialophora bantiana is remarkable in consistently having introns in its 18S rDNA gene. PMID- 9988493 TI - Development of vaccines and their use in the prevention of fungal infections. AB - Vaccine approaches to infectious diseases are widely applied and appreciated. Disciplines such as bacteriology and virology have a rich history of successful vaccine development. The complexity of eukaryotic systems presents additional challenges to the development of vaccines against them. These challenges are being met in the fields of parasitology, and are being revisited for application in oncology. Vaccine opportunities exist in medical mycology. The National Institute of Allergy and Infectious Diseases has held a series of workshops in medical mycology where the need to develop vaccines for fungal diseases was noted and where important opportunities were discussed. Major advances in vaccinology and the technology of antigen preparation and delivery have increased feasibility and heightened interest. The recent epidemic of coccidioidomycosis in the American Southwest has demonstrated the need for developing a vaccine as an effective preventive measure for those living in and for those who subsequently move into regions with the endemic mycoses. The XIIth Congress of the International Society for Human and Animal Mycology included a symposium that summarized new vaccination strategies for selected fungi: Candida albicans, Coccidioides immitis, and Trichophyton verrucosum. The goal of the present summary is to provide representative examples of continuing efforts relating to vaccine development within the medical mycological community highlighting Blastomyces dermatidis, Cryptococcus neoformans, Histoplasma capsulatum, Paracoccidioides brasiliensis, and Pythiumn insidiosum. PMID- 9988494 TI - Standardization of antifungal susceptibility testing and clinical relevance. AB - Standardization of antifungal susceptibility testing became essential to overcome the problem of interlaboratory variability and to determine the clinical relevance of in vitro data. This evolving process began for the yeasts and consequently broth macrodilution and microdilution methods (NCCLS M27 document) have been developed. These tests may not be useful for testing all organism-drug combinations or be the most convenient techniques for routine use in the clinical laboratory. Different alternatives to the NCCLS methods are currently under investigation. The identification of standard guidelines for antifungal susceptibility testing has reduced interlaboratory variability and further progress has been achieved with the determination of tentative interpretive breakpoints for certain drug-yeast combinations. However, these breakpoints are not adequate for interpretations of MICs for fungi-drug combinations beyond the setting for which they were determined. The NCCLS Subcommittee has also generated data for proposed testing guidelines for the moulds. PMID- 9988495 TI - Cryptococcus neoformans: virulence and host defences. AB - Cryptococcus neoformans represents a model organism for the study of virulence and the host response. In this discussion, there is a focus on the genetic, molecular, and biochemical aspects of C. neoformans as it interacts with the host. Investigations into direct and indirect virulence phenotypes are now possible. The molecular aspects of two major virulence factors, capsule and melanin, are characterized. Yeast polyol metabolism through mannitol is examined as a potential biochemical pathway for virulence. The concept of C. neoformans differentially expressed genes within the host or in response to certain environmental cues can be used indirectly to identify potential virulence genes. However, despite significant progress in molecular pathogenesis with C. neoformans, the future of research in this area will require a certain critical mass of investigators to help share in the developmental costs which continue to occur. PMID- 9988496 TI - Imported mycoses in Europe. AB - This article reviews the clinical manifestations, diagnosis and management of some of the more important systemic infections that are now being imported into Europe. It also considers the risks some of the causal organisms pose to European laboratory workers, many of whom are unfamiliar with the precautions that should be taken when handling these pathogens. PMID- 9988497 TI - Antibody and/or cell-mediated immunity, protective mechanisms in fungal disease: an ongoing dilemma or an unnecessary dispute? AB - Historically there has been controversy on the relative importance of antibody- and cell-mediated immune responses in the protection against fungal pathogens. The controversy was fuelled by the difficulties encountered in obtaining consistent results with polyclonal antibody experiments and I inducing long lasting immune protection by vaccinations with induce stron cell-mediated responses. Recent studies indicate that both antibody- and cell-mediated immune responses can contribute to host protection against Candida albicans and C. neoformans. At the present time the major issue is not the relative importance of antibody- and cell-mediated immune responses but rather, the mechanisms by which the two arms of the immune system function and cooperate. PMID- 9988498 TI - Teaching medical mycology in the year 2000. AB - Medical mycology is of increasing interest to the basic scientist, pathologist, microbiologist and clinician. This interest has been prompted by the rising number of immunosuppressed patients with opportunistic fungal infections, the expanding boundaries of the so-called endemic mycoses, the recognition of several major new endemic mycoses and a variety of other emerging fungal infections, and the development of potent, non-toxic antifungal drugs to treat these infections. The world of mycology is changing dramatically, especially in developing countries which have only limited resources to cope with the impact of the compromised host and the introduction of costly new antifungal drugs. Consequently, there is an urgent need to increase our effectiveness as teachers of medical mycology at all levels and in all regions of the world. PMID- 9988499 TI - Type 1 and type 2 cytokines: from basic science to fungal infections. AB - At the present time, it is clear that Th1 responses afford protection against the fungi; however, the development, maintenance and function of the protective immune responses are complex mechanisms and are influenced by multiple factors. The route of infection has been shown to affect initial cytokine production and, consequently, the induction of protective Th1 responses. The ability of different isolates of the same fungal agent to induce and sustain a protective response has also been emphasized. Protective immune responses have been shown to vary in genetically different mouse strains after infection. In addition, these protective responses, such as cellular influx and cytokine production, also vary within the same animal depending on the tissue infected. The functional dominance of certain cytokines over others in influencing development and maintenance of protective responses has been discussed. Certain cytokines may act differently in hosts lacking important components of their innate or immune repertoire. It is evident from these presentations that a more comprehensive understanding of the protective mechanisms against different fungal agents is emerging. However, there is still much to learn before cytokine modulatory therapy can be used effectively without risk in the human host. PMID- 9988500 TI - Antifungal drug resistance in pathogenic fungi. AB - Failures of drug treatment in fungal infections combined with improvements in performances and standardization of antifungal susceptibility testing have drawn attention to the problem of antifungal resistance and its underlying mechanisms. Resistance of Candida species and Cryptococcus neoformans to flucytosine (5FC) develops during monotherapy. Acquired resistance results from a failure to metabolize 5FC to 5FUTP and 5FdUMP, or from the loss of feedback control of pyrimidine biosynthesis. A combination of 5FC and amphotericin B (AmB) reduces the appearance of resistant C. albicans isolates. Resistance to AmB is unusual. C. lusitaniae is the most susceptible to AmB resistance. C. neoformans with decreased AmB susceptibility has been isolated from an HIV-infected patient. Acquired resistance to AmB is often associated with alteration of membrane lipids, especially ergosterol. Concomitant with the widespread use of fluconazole there have been increasing reports of fluconazole resistance in Candida species and C. neoformans. Fluconazole resistance was mostly associated with prior use of fluconazole as intermittent therapy or prophylactic continuous treatment for recurrent thrush. In contrast to fluconazole, itraconazole is active against C. krusei. Decreased susceptibility to itraconazole is observed over time in C. albicans isolates becoming resistant to fluconazole. Decreased susceptibility to itraconazole and SCH-56592 was also observed in a few Aspergillus fumigatus isolates. Failure to accumulate azole antifungals has been identified as a cause of resistance in several post-treatment C. albicans, C. glabrata and C. krusei isolates. In azole-resistant C. albicans isolates from AIDS patients with oropharyngeal candidiasis, multidrug efflux transporters of the ATP-binding cassette (ABC) superfamily and of the class of major facilitators (MF) have been shown to be responsible for the low level of accumulation of azole antifungal agents. Two genes for these transporters, the ABC-transporter gene CDR1 and the MF gene, CaMDR1 (BEN) were shown to be overexpressed in resistant C. albicans isolates. Overexpression of BEN in Saccharomyces cerevisiae conferred resistance to fluconazole and terbinafine. CDR1 overexpression in S. cerevisiae conferred cross-resistance to fluconazole, itraconazole, ketoconazole and terbinafine. C. albicans clinical isolates resistant to azole antifungal agents over-expressing the ABC-transporter genes CDR1 and CDR2 were less susceptible to the morpholine derivative amorolfine. In C. glabrata isolates azole resistance is based on over expression of the CgCDR gene. A reduced susceptibility of ergosterol biosynthesis is another mechanism of resistance described in a number of post-treatment C. albicans, C. neoformans and Histoplasma capsulatum isolates. Mutations have been reported in the CYP51A1 genes of resistant C. albicans isolates. Over-expression of CYP51A1 in C. albicans and C. glabrata may also account for a decreased susceptibility to azole antifungal agents. PMID- 9988501 TI - Selected animal models: vaginal candidosis, Pneumocystis pneumonia, dermatophytosis and trichosporosis. AB - A clear understanding of the pathogenesis of fungal disease remains elusive. While technological advances in molecular biology and microbial genetics have provided scientists with major new insights into both microbial virulence factors as well as host susceptibility to infection, there is currently no substitute for animal models in elucidating microbe-host interactions. Animal models are also essential for the evaluation of new antimicrobial agents, including studies of efficacy, adverse reactions and pharmacokinetics. The single most important advance in animal models in the last decade, has been the availability of genetically unique strains of animals as alternative to animals treated with immunosuppressive drugs for use in studies on microbial virulence and host defence mechanisms. These unique strains of test animals also enhance our understanding of the modes of action of antifungal drugs and their metabolism. Some of these advances will be discussed in this symposium. PMID- 9988502 TI - Mycological control and surveillance of biological waste and compost. AB - This paper presents some recent developments regarding current work on hygienic aspects, in particular the presence and dispersion of fungi (e.g. Aspergillus fumigatus), of biological waste and compost. PMID- 9988503 TI - Current trends in the detection of antigenaemia, metabolites and cell wall markers for the diagnosis and therapeutic monitoring of fungal infections. AB - There have been several recent developments in the diagnosis of fungal infections, including the production of novel antigen detection tests, the G test, and assays for the detection of fungal metabolites. In this article we present an overview of these developments and examine the value of including these tests in clinical trials. PMID- 9988504 TI - Importance of Candida species other than Candida albicans as opportunistic pathogens. AB - Candida species other than C. albicans have become a significant cause of infection in humans. Several of the more commonly isolated of these species are less susceptible to commonly used azole antifungal drugs, a factor that poses significant difficulties for effective treatment. The modern mycology laboratory has an important role to play in several aspects relating to these organisms, including therapy, detection, identification and epidemiological analysis. The application of molecular techniques and phylogenetic analysis has led to the identification of a new species of Candida associated with mucosal candidiasis in HIV-infected individuals named Candida dubliniensis, the clinical significance of which is currently under investigation. Molecular techniques are also being applied to the analysis of determinants involved in pathogenicity of species such as Candida glabratta. These approaches should lead to a better understanding of these organisms and there ability to cause disease and should also provide more effective treatment. PMID- 9988505 TI - Dermatophytes and host defence in cutaneous mycoses. AB - Dermatophytosis is the infection of keratinized tissues such as hair, nails and the stratum corneum of the skin by dermatophyte fungi. These fungi are onygenalean anamorphs and anamorphic species belonging to the genera Trichophyton, Microsporum and Epidermophyton. An important characteristic of the dermatophytes as parasites is their restriction to the dead keratinized tissues, except in rare cases where the patient is immunosuppressed. In contrast to many fungi, including normally non-pathogenic species, which can invade systemically in severely immunocompromised (e.g. neutropenic) patients, dermatophytes appear to be unable to cause systemic infection in this population. Thus, these fungi appear to have an unique interaction with the immune system. A better understanding of this interaction will contribute significantly to our knowledge of mammalian host defences. PMID- 9988506 TI - Cytokines and mycoses. AB - Cell-mediated immunity (CMI) has been shown, over many decades of clinical observation and bench research, to be central to the outcome of invasive fungal infections. In recent years, understanding the role of messenger molecules (cytokines), in coordinating and augmenting cellular immunity has been ascendant. These studies have made it possible to consider using cytokines, now available in abundant quantities via recombinant DNA technologies, to treat fungal infections. In this symposium, the most important fungal pathogens that cause infections in humans, particularly in immunocompromised patients, are considered, with emphasis on how recent experimental work may lead to a better understanding of the role of cytokines and their use in therapy. PMID- 9988507 TI - Genetics, metabolism and host specificity of Pneumocystis carinii. AB - Pneumocystis carinii is a major cause of severe pneumonia in immunosuppressed individuals, especially in those with human immunodeficiency virus (HIV) infection during their period of progression to acquired immunodeficiency syndrome (AIDS), and constitutes a worldwide problem to public health. Recently, significant advances in the development of experimental animal models of P. carinii infection, as well as in our knowledge of the genetic diversity and taxonomy of P. carinii, have been made. These advances may contribute to our understanding of the transmission of P. carinii pneumonia (PCP) and to the development of new prevention and control strategies. This paper addresses questions relating to the epidemiology of PCP including the detection of the parasite in the environment and in patients, the mechanism of genetic variation of the major surface glycoprotein (MSG) of P. carinii, and host-related genetic variation among isolates of this organism, emphasizing phenotypic expression and its impact on epidemiology and taxonomy. PMID- 9988508 TI - New approaches to antifungal chemotherapy. AB - The antifungal agents currently available to treat invasive fungal infections are limited in both number and usefulness. Treatment with the polyene amphotericin B (AmB), and with several azoles, in particular fluconazole and itraconazole, is the mainstay of antifungal chemotherapy. However, the clinical usefulness of these drugs is hampered by drawbacks associated with their safety and/or efficacy. There are two approaches to overcome this situation. One is to discover and develop new antifungal agents or formulations with advantages over and/or complementary to existing drugs. For this purpose, the following three categories of new drugs have been the major targets of study and development: (i) lipid formulations of polyenes, (ii) azoles (including cyclodextrin-complexes), and (iii) nonazole compounds, particularly those of microbial origin (antibiotics). PMID- 9988509 TI - Recent advances in cryptococcosis, candidiasis and coccidioidomycosis complicating HIV infection. AB - Concomitant with the decline in CD4+ T-cells seen as human immunodeficiency virus (HIV) infection progresses, the prevalence of opportunistic mycoses increases dramatically. This article reviews selected recent advances in our understanding of the immunology, molecular epidemiology and treatment of fungal infections in patients infected with HIV. For cryptococcosis, studies are reported on how HIV infection affects the immune response to Cryptococcus neoformans and, conversely, how stimulation with C. neoformans induces HIV production from latently HIV infected cells. In addition, studies are presented examining the efficacy of triple combination antimycotic chemotherapy in cryptococcosis. For candidosis, investigations into genetic profiles of Candida albicans isolates obtained from patients, with resistance to antifungal agents, are demonstrated. Finally, for coccidioidomycosis, prospective studies are presented examining the clinical, epidemiological and immunological characteristics of a cohort of HIV-infected subjects residing in an endemic area. PMID- 9988510 TI - Mycoses of fish. PMID- 9988511 TI - The role of Malassezia species in the ecology of human skin and as pathogens. AB - The new taxonomic structure of the lipophilic genus Malassezia was presented with key characteristics for the seven described species. Among techniques used for epidemiological surveys, the pulsed field gel electrophoresis (PFGE) was found to be of little value in contrast to randomly amplified polymorphic DNA (RAPD). Immunological studies still yielded conflicting results but at least the immunomodulatory capacity of Malassezia yeasts appeared to be related to the cell wall lipids. A review of Malassezia infections together with the present consensus for their prevention and treatment was also made. PMID- 9988512 TI - Advances in molecular genetics of Candida albicans and Candida glabrata. AB - Ten years ago, when molecular genetic methods were being applied vigorously to viruses, bacterial pathogens and eukaryotic parasites, there seemed to be a partial paralysis in applying them to infectious fungi; this state of affairs was more than apparent in the composition of the symposia at the ISHAM conference in 1987. Since then, however, things have changed. The ISHAM conference held in Italy in 1997 was replete with studies utilizing molecular genetic techniques to answer questions related to epidemiology, pathogenesis, drug development and typing. In the symposium Advances in Molecular Genetics of Fungal Pathogens, several new applications of molecular biology to fungal pathogenesis were reviewed. Although the presentations in this symposium covered only a fraction of the molecular methods now being applied to Candida pathogenesis, they nevertheless provided an intriguing view of what is in store for us in the coming years. PMID- 9988513 TI - Molecular mechanisms of virulence in fungus-host interactions for Aspergillus fumigatus and Candida albicans. AB - Research on fungi that cause opportunistic infections has increased dramatically during the past few years, largely because these organisms cause significant morbidity and mortality. Most of this research has focused on defining the virulence factors produced by these pathogens, as well as developing methods for the diagnosis of fungal diseases. With regard to studies on the biology of Candida albicans, it is now possible to isolate genes, disrupt their expression, and observe the specific effects of gene disruption on virulence and growth of the organism. Moreover, growth and virulence of this pathogen is also being studied and the effect of environmental factors on gene expression investigated. This subject is especially important in view of the fact that C. albicans can colonize and invade a number of sites in the human body. Thus, its ability to grown in the oral and vaginal tracts, as well as in blood, requires the organism to adapt to a variety of environmental stresses. Here we present observations on the growth, morphogenesis and virulence of the opportunistic fungi C. albicans and Aspergillus fumigatus. PMID- 9988514 TI - Molecular diagnosis and epidemiology of fungal infections. AB - A variety of methods are utilized for DNA strain subtyping of Candida spp. because no 'gold standard' exists. Random amplified polymorphic DNA (RAPD) or restriction enzyme analysis (REA) are useful to determine the source of an outbreak, but more reproducible and discriminatory methods such as Southern hybridization and pulsed field gel electrophoresis (PFGE) may be required. When applied to some nosocomial Candida infections, multiple strains and species have been identified. Microevolution of yeast species occurs and epidemiologically related isolates may show minor pattern differences, creating uncertainty as to whether they are distinct strains. Approximately 1000 isolates of Aspergillus fumigatus from environmental and clinical sources were typed by REA probed with an A. fumigatus-specific retrotransposon-like sequence. Patients with no symptom of aspergillosis may carry several strains, whereas patients with pulmonary aspergillosis may carry one or two strains; nocosomial transmission of aspergillosis was proven in 39% of the patients studied; any given environmental strain can be infectious; the environmental population of A. fumigatus is extremely diverse and no specific niche was found in the hospital. A PCR assay was designed to target conserved 18S-ribosomal DNA (rDNA) sequences shared by most fungi and a 687 bp product was amplified from 25 medically important fungal species. Studies with blood, cerebrospinal fluid and sputum specimens from patients with mycoses indicated that the PCR assay is more sensitive in diagnosing invasive fungal infections than blood culture methods. More specific identification is obtainable with genus/species-specif c probes designed from within the PCR-amplified sequences for C. albicans, C. krusei, C. lusitaniae, Pneumocystis carinii, Cryptococcus neoformans, Aspergillus/Penicillium spp. and C. glabrata/Saccharomyces cerevisiae. A. fumigatus and A. niger were differentiated by denaturing gradient gel electrophoresis. In situ hybridization (ISH) detected a 648 bp fragment of the 18S rDNA of C. neoformans and a 568 bp fragment of the alkaline proteinase gene of A. fumigatus in tissues from experimentally infected animals. In ISH, the entire process can be automated, making this procedure rapid and easy. The difficulty in establishing a diagnosis of invasive candidiasis has prompted the quest for a clinically useful PCR test for candidaemia. The universal fungal oligonucleotide primer pair, ITS3 and ITS4, amplifies portions of the 5.8S ad 28S rDNA subunits, and the ITS2 region. Although rRNA genes are highly conserved, the ITS regions are distinctive. DNA probes were designed from ITS2 that were specific for 16 different Candida species. Simple, rapid sample preparation was suitable for PCR analysis of BacT/Alert blood culture bottles. Sample preparation, PCR, and EIA detection of the amplicon from five different Candida species was accomplished in 7 h, 2.5 days sooner than by conventional culture methods. As well as saving time, minor yeast species among a major species, or among bacteria, were simultaneously detected. PCR-EIA using a microtitration plate format had sensitivity 10-times greater than that obtained with ethidium bromide-stained agarose gels. Taqman combines in one step PCR, probe hybridization, and fluorescent signal generation. Taqman PCR had sensitivity equivalent to PCR-EIA and required only 5 h, including sample preparation. PMID- 9988515 TI - Biosafety considerations in handling medically important fungi. AB - Over 500,000 workers in the USA alone are employed in laboratories that range from small physician offices to large clinical laboratories handling microbes for comprehensive research and/or diagnostic work. These workers are exposed to a variety of potential occupational health risks such as exposure to infectious clinical materials, environmental specimens, cultures, complex and inflammable chemicals, radiation, and electrical and mechanical hazards. As members of the International Society for Human and Animal Mycology, we have no policy statement on biosafety standards for handling medically important fungi. The intent of the symposium is to cover some of the important aspects of biosafety; (1) standards in handling dimorphic fungal pathogens; (2) the principles and criteria of biosafety levels and classification of known medically important fungi, aerobic actinomycetes, environmental fungi according to their biosafety levels; (3) medically important fungal waste and its safe disposal; and (4) biosafety and regulatory considerations in handling and mailing medically important fungi in a culture collection. PMID- 9988516 TI - The role of ISHAM: how developing and developed countries can benefit from it. International Society for Human and Animal Mycology. AB - The international community of mycologists, ISHAM, is faced increasingly with the needs and demands of supporting the development of organizational structures worldwide in the field of medical mycology. This goes beyond the classical objectives of a scientific association, namely organizing international congresses and publishing a journal. In the early part of the next century, this will become a major challenge to ISHAM. Symposia discussing this subject were presented at the 12th Congress of ISHAM held in Adelaide, Australia, in 1994. This paper outlines the reflections and discussions held by members of our Society in 1997. PMID- 9988517 TI - Parasitic relationship between Microsporum canis and the cat. AB - Cats are often cited as reservoirs of M. canis but it is questionable whether M. canis is part of the resident flora of the cat's skin and hair or only a transient organism. Studies indicate that M. canis is most often isolated from cats at risk of infection or exposure from other infected cats or from a contaminated environment. Many more cats are culture-positive for M. canis than have dermatophytosis. Culture isolation alone is not an indication of dermatophytosis; the diagnosis of dermatophytosis requires microscopic evidence of infection as well as culture evidence of the presence of the dermatophyte. The cat's hair coat adopts the culture image of its surroundings. Diverse factors may influence the frequency of isolation of M. canis. Nevertheless, isolation of M. canis implies either active disease or fomite carriage and warrants aggressive investigation of the clinical situation. PMID- 9988518 TI - Technology transfer and application in the clinical mycology laboratory for the 21st century: potential for transfer and application of new technologies in routine laboratory operations--industrialized countries. PMID- 9988519 TI - An intriguing controversy over protein structural class prediction. AB - A recent report by Bahar et al. [(1997), Proteins 29, 172-185] indicates that the coupling effects among different amino acid components as originally formulated by K. C. Chou [(1995), Proteins 21, 319-344] are important for improving the prediction of protein structural classes. These authors have further proposed a compact lattice model to illuminate the physical insight contained in the component-coupled algorithm. However, a completely opposite result was concluded by Eisenhaber et al. [(1996), Proteins 25, 169 179], using a different dataset constructed according to their definition. To address such an intriguing controversy, tests were conducted by various approaches for the datasets from an objective database, the SCOP database [Murzin et al. (1995), J. Mol. Biol. 247, 536-540]. The results obtained by both self-consistency and jackknife tests indicate that the overall rates of correct prediction by the algorithm incorporating the coupling effect among different amino acid components are significantly higher than those by the algorithms without counting such an effect. This is fully consistent with the physical reality that the folding of a protein is the result of a collective interaction among its constituent amino acid residues, and hence the coupling effects of different amino acid components must be incorporated in order to improve the prediction quality. It was found by a revisiting the calculation procedures by Eisenhaber et al. that there was a conceptual mistake in constructing the structural class datasets and a systematic mistake in applying the component-coupled algorithm. These findings are informative for understanding and utilizing the component-coupled algorithm to study the structural classes of proteins. PMID- 9988520 TI - Partial in vitro digestion of active gliadin-related peptides in celiac disease. AB - Peptides corresponding to residues 75-86 (RPQQPYPQPQPQ) and 75-85 of the A gliadin structure, which were shown to be active in an animal model of celiac disease, were digested in vitro with small intestinal mucosa from children with celiac disease in remission and with mucosa from normal children. The products of digestion were separated into two fractions by gel permeation chromatography. Undigested residues (Mr > 400 fraction) from both peptides contained mainly glutamine, proline, and tyrosine, while the digested materials (Mr < 400 fraction) contained mainly proline, glutamine and arginine. Much larger amounts of undigested peptides were obtained from digestion with celiac mucosa than from normal mucosa. The results with peptide 75-86 indicated that the octapeptide 77 84 (QQPYPQPQ) was the main residual component and this peptide was shown to be active in the assay. Peptide 77-84 was also obtained as a residue from digestion of peptide 75-85, together with heptapeptide 77-83. The results lend further support for a primary mucosal defect in celiac disease and indicate that residual peptides in the small intestine of patients with the disease still retain appreciable toxicity. PMID- 9988521 TI - The sequential mechanism of guanidine hydrochloride-induced denaturation of cAMP receptor protein from Escherichia coli. A fluorescent study using 8-anilino-1 naphthalenesulfonic acid. AB - cAMP receptor protein (CRP) regulates expression of a number of genes in Escherichia coli. The protein is a homodimer and each monomer is folded into two structural domains. The biological activation of CRP upon cAMP binding may involve the subunit realignment as well as reorientation between the domains within each subunit. In order to study the interactions between the subunits or domains, we performed stopped-flow measurements of the guanidine hydrochloride (GuHCI)-induced denaturation of CRP. The changes in CRP structure induced by GuHCl were monitored using both intrinsic Trp fluorescence as well as the fluorescence of an extrinsic probe, 8-anilino-1-Naphthalenesulfonic acid (ANS). Results of CRP denaturation using Trp fluorescence detection are consistent with a two-step model [Malecki, and Wasylewski, (1997), Eur. J. Biochem. 243, 660], where the dissociation of dimer into subunits is followed by the monomer unfolding. The denaturation of CRP monitored by ANS fluorescence reveals the existence of two additional processes. One occurs before the dissociation of CRP into subunits, whereas the second takes place after the dissociation, but prior to proper subunit unfolding. These additional processes suggest that CRP denaturation is described by a more complicated mechanism than a simple three state equilibrium and may involve additional changes in both inter- and intrasubunit interactions. We also report the effect of cAMP on the kinetics of CRP subunit unfolding and refolding. PMID- 9988522 TI - Interactions between NFkappaB and its inhibitor ikappaB: biophysical characterization of a NFkappaB/ikappaB-alpha complex. AB - The N-terminal domain (1-318 amino acids) of mouse NFkappaB (p65) has been purified to homogeneity from the soluble fraction of Escherichia coli cells expressing this protein. Its complex with a full-length ikappaB-alpha (MAD3, 1 317 amino acids) molecule was generated by binding the E. coli-derived ikappaB alpha to the purified NFkappaB and purifying the complex by sequential chromatography. The stoichiometry of NFkappaB to ikappaB in the complex was determined to be 2 to 1 by light scattering and SDS-polyacrylamide gel electrophoresis. The secondary structure of the NFkappaB (p65) determined by Fourier-transform infrared (FTIR) spectroscopy is in good agreement with that of the p50 in the crystal structure of the p50/DNA complex, indicating that no significant structural change in NFkappaB occurs upon binding of DNA. The FTIR spectrum of the NFkappaB/ikappaB complex indicates that its secondary structure is composed of 17% alpha-helix, 39% beta-strand, 18% irregular structures, and 26% beta-turns and loops. By comparing these data to the FTIR data for NFkappaB alone, it is concluded that the ikappaB (MAD3) in the complex contains 35% alpha helix, 27% beta-strand, 22% irregular structures, and 16% beta-turns and loops. Circular dichroism (CD) analysis of a shorter form of ikappaB (pp40) indicates that it contains at least 20% alpha-helix and that the ikappaB subunit accounts for nearly all of the alpha-helix present in the NFkappaB/ikappaB complex, consistent with the FTIR results. The stabilities of NFkappaB, ikappaB, and their complex against heat-induced denaturation were investigated by following changes in CD signal. The results indicate that the thermal stability of ikappaB is enhanced upon the formation of the NFkappaB/ikappaB complex. PMID- 9988523 TI - Molecular dynamics simulation of protein folding with supersecondary structure constraints. AB - We integrate molecular dynamics simulation methods with a newly developed supersecondary structure prediction method and compute the structure of a protein molecule, crambin. The computed structure is similar to the crystal structure with an rms error of 3.94 A. PMID- 9988524 TI - The polymer basis of kinetics and equilibria of enzymes: the accessible-volume origin of entropy changes in a class Abeta-lactamase. AB - The occurrence of enzymatic catalysis, as for any chemical reaction, depends critically upon close contact of the reactants, since making/breaking of bonds occurs over distances of about 0.2 A. Unlike small molecules, each enzyme molecule acts as an ordered solvent and reactant. Each group important to the enzyme reaction interacts with the substrate, then moves away, and subsequently binds another substrate. In other words, the group undergoes round trips in structure. For a round trip, the thermochemical state functions deltaG, deltaH, deltaS, etc., are zero. As a consequence, control of the binding of substrate must reside in the nonbinding conformations of the polymer since they govern the different fractions of time the macromolecule is in the correct conformation for bonding. Applying standard macromolecular models to the enzymes suggests that the majority of free energy for an enzyme reaction resides in the enzyme structure as an entropic contribution. Enthalpic contributions come from bond formation with the substrates and substrate structural changes. Further, it is shown that the molecular mechanisms that can effect binding and allosteric control fall into only three classes. Three x-ray structures of class A beta-lactamases (native, mutant, and with substrate) show the individual binding groups at the active site change their accessible volumes depending on substrate binding and mutant form. From these volume differences, the deltaS of reaction is calculated. The x-ray derived deltaG = - TdeltaS matches the deltaG = -RT ln k1 from changes in rate constants for the same set of beta-penicillinases. PMID- 9988525 TI - Partially folded conformations of inositol monophosphatase endowed with catalytic activity. AB - The stability of porcine brain inositol monophosphatase in the presence of increasing concentrations of urea was investigated at pH 7.5. Exposure of the enzyme to 8 M urea brings about the dissociation of the dimeric species of 58 kDa into monomeric forms as revealed by gel filtration chromatography. Unfolding of the protein by 8 M urea results in a decrease of the ellipticity at 220 nm (20%) together with a perturbation of the near-UV circular dichroism spectrum. Urea treated inositol monophosphatase binds Co2+ ions with a dissociation constant of 3.3 microM. The enzyme is catalytically competent when assayed with 4-nitrophenyl phosphate in the presence of the activating ion Co2+ at pH 7.5 in 8 M urea. The apparent activation constant for Co2+ is 2.5 mM. It is postulated that partially folded conformations of monomeric species preserve their catalytic function because the affinity of Co2+ ions for the metal coordination center of the protein is not perturbed by exposure to 8 M urea. PMID- 9988526 TI - Isolation and properties of a new kallikrein inhibitor from Tityus serrulatus venom. AB - The kallikrein inhibitor-peptide content of Tityus serrulatus scorpion crude venom was purified by Sephadex G-50 and Sephadex G-25 fine gel filtration chromatographies, followed by two steps of reverse-phase column on HPLC. The isolated inhibitor peptide was homogeneous in its N-terminal and partial amino acid sequence, showing a molecular weight of 4.489 Da by mass spectrometry and amino acid analysis. The peptide was tested with rat plasma and urine kallikrein, which resulting in an inhibition with similar affinity to both enzymes, showing an IC50 of 14.3 microM after 13 and 8 min, respectively, using kininogen as substrate on the isolated guinea-pig ileum bioassay. The porcine pancreatic kallikrein showed after 10 min an IC50 value of 12.6 microM with H-D-Val-Leu-Arg pNA HCl as substrate. In addition, the isolated peptide significantly inhibited porcine pancreatic kallikrein with values in the range of apparent or absolute calculated peptide Ki = 2.5 microM. The inhibitor was heat resistant and stable at pH values less than 5. PMID- 9988527 TI - Analysis of heparin-binding sites in human lipoprotein lipase using synthetic peptides. AB - Synthetic nonbasic peptides based on the type I repeats of thrombospondin (TSP) and four peptides corresponding to the predicted basic clusters in lipoprotein lipase (LPL) have been analyzed for heparin binding. In the present report we examine the structural requirement for the binding of these peptides to heparin Sepharose column. The peptide containing the sequence Phe-Ser-Trp-Ser-Asp-Trp-Trp Ser (residues 388-395 in lipoprotein lipase, which include the consensus TSP type I sequence) showed strong binding to heparin. Both the first and second Trp residues in this sequence were essential for tight heparin binding. Substitution of either of the Trp residues by an Ala resulted in the complete loss of heparin binding. The peptides representing the four basic cluster regions of lipoprotein lipase showed variable heparin binding. Strong retention was observed for peptides representing cluster 1 (residues 261-287) and cluster 3 (residues 147 151) peptides followed by cluster 2 (residues 290-302) peptide. A peptide corresponding to LPL cluster 4 (residues 405-414) did not show binding to heparin column. The present study confirms the presence of specific heparin-binding sites in LPL. Furthermore, this study also demonstrates the potential use of synthetic peptides to investigate the interaction between peptides and heparin as an alternative approach to site-directed mutagenesis in selected regions of large protein molecules. The affinity of these peptides toward heparin can be explored to block molecular interactions at these specific sites or to carry and deliver other coupled molecules at the site(s) of attachment of these peptides for therapeutic applications. PMID- 9988528 TI - Amino acid sequence, spectral, oxygen-binding, and autoxidation properties of indoleamine dioxygenase-like myoglobin from the gastropod mollusc Turbo cornutus. AB - Myoglobin was isolated from the radular muscle of the archaeogastropod mollusc Turbo cornutus (Turbinidae). This myoglobin is a monomer carrying one protoheme group; the molecular mass was estimated by SDS-PAGE to be about 40 kDa, 2.5 times larger than that of usual myoglobin. The cDNA-derived amino acid sequence of 375 residues was determined, of which 327 residues were identified directly by chemical sequencing of internal peptides. The amino acid sequence of Turbo myoglobin showed no significant homology with any other usual 16-kDa globins, but showed 36% identity with the myoglobin from Sulculus diversicolor (Haliotiidae) and 27% identity with human indoleamine 2,3-dioxygenase, a tryptophan-degrading enzyme containing heme. Thus, the Turbo myoglobin can be counted among the myoglobins which evolved from the same ancestor as that of indoleamine 2,3 dioxygenase. The absorbance ratio of gamma to CT maximum (gamma/CT) of Turbo metmyoglobin was 17.8, indicating that this myoglobin probably possesses a histidine residue near the sixth coordination position of heme iron. The Turbo myoglobin binds oxygen reversibly. Its oxygen equilibrium properties are similar to those of Sulculus myoglobin, giving P50 = 3.5 mm Hg at pH 7.4 and 20 degrees C. The pH dependence of autoxidation of Turbo oxymyoglobin was quite different from that of mammalian myoglobin, suggesting a unique protein folding around the heme cavity of Turbo myoglobin. A kinetic analysis of autoxidation indicates that the amino acid residue with pKa = 5.4 is involved in the reaction. The autoxidation reaction was enhanced markedly at pH 7.6, but not at pH 5.5 and 6.3 in the presence of tryptophan. We suggest that a noncatalytic binding site for tryptophan, in which several dissociation groups with pKa > or = 7.6 are involved, remains in Turbo myoglobin as a relic of molecular evolution. PMID- 9988529 TI - The complete amino acid sequence of a trypsin inhibitor from Bauhinia variegata var. candida seeds. AB - Trypsin inhibitors of two varieties of Bauhinia variegata seeds have been isolated and characterized. Bauhinia variegata candida trypsin inhibitor (BvcTI) and B. variegata lilac trypsin inhibitor (BvlTI) are proteins with Mr of about 20,000 without free sulfhydryl groups. Amino acid analysis shows a high content of aspartic acid, glutamic acid, serine, and glycine, and a low content of histidine, tyrosine, methionine, and lysine in both inhibitors. Isoelectric focusing for both varieties detected three isoforms (pI 4.85, 5.00, and 5.15), which were resolved by HPLC procedure. The trypsin inhibitors show Ki values of 6.9 and 1.2 nM for BvcTI and BvlTI, respectively. The N-terminal sequences of the three trypsin inhibitor isoforms from both varieties of Bauhinia variegata and the complete amino acid sequence of B. variegata var. candida L. trypsin inhibitor isoform 3 (BvcTI-3) are presented. The sequences have been determined by automated Edman degradation of the reduced and carboxymethylated proteins of the peptides resulting from Staphylococcus aureus protease and trypsin digestion. BvcTI-3 is composed of 167 residues and has a calculated molecular mass of 18,529. Homology studies with other trypsin inhibitors show that BvcTI-3 belongs to the Kunitz family. The putative active site encompasses Arg (63)-Ile (64). PMID- 9988530 TI - The primary structure of water buffalo alpha(s1)- and beta-casein identification of phosphorylation sites and characterization of a novel beta-casein variant. AB - The primary structure of water buffalo alpha(s1)-casein and of beta-casein A and B variants has been determined using a combination of mass spectrometry and Edman degradation procedures. The phosphorylated residues were localized on the tryptic phosphopeptides after performing a beta-elimination/thiol derivatization. Water buffalo alpha(s1)-casein, resolved in three discrete bands by isoelectric focusing, was found to consist of a single protein containing eight, seven, or six phosphate groups. Compared to bovine alpha(s1)-casein C variant, the water buffalo alpha(s1)-casein presented ten amino acid substitutions, seven of which involved charged amino acid residues. With respect to bovine betaA2-casein variant, the two water buffalo beta-casein variants A and B presented four and five amino acid substitutions, respectively. In addition to the phosphoserines, a phosphothreonine residue was identified in variant A. From the phylogenetic point of view, both water buffalo beta-casein variants seem to be homologous to bovine betaA2-casein. PMID- 9988531 TI - Characterization of the binding sites for plasminogen and tissue-type plasminogen activator in cytokeratin 8 and cytokeratin 18. AB - Cytokeratin 8 (CK8) is an intermediate filament protein that penetrates to the external surfaces of breast cancer cells and is released from cells in the form of soluble heteropolymers. CK8 binds plasminogen and tissue-type plasminogen activator (t-PA) and accelerates plasminogen activation on cancer cell surfaces. The plasminogen-binding site is located at the C-terminus of CK8. In this study, we prepared GST-fusion proteins which contained either 174 amino acids from the C terminus of CK8 (CK8f) or 134 amino acids from the C-terminus of CK18 (CK18f). A third GST-CK fusion protein was identical to CK8fexcept that the C-terminal lysine was mutated to glutamine (CK8fK483Q). CK8f bound plasminogen; the K(D) was 0.5 microM. Binding was completely inhibited by epsilonACA. CK8fK483Q also bound plasminogen, albeit with decreased affinity (K(D) approximately 1.5 microM). CK18f did not bind plasminogen at all. All three fusion proteins bound t-PA equivalently, providing the first evidence that CK18 may function as a t-PA receptor, t-PA and plasminogen cross-competed for binding to CK8f. Thus, t-PA and plasminogen cannot bind to the same CK8f monomer simultaneously. Nevertheless, CK8f still promoted plasminogen activation, probably reflecting the fact that CK8f was purified in dimeric or tetrameric form. These studies demonstrate that CK8 may promote plasminogen activation by t-PA only when present in an oligomerized state. CK18 may participate in the oligomer, together with CK8, based on its ability to bind t-PA. PMID- 9988532 TI - A model of the quaternary structure of enolases, based on structural and evolutionary analysis of the octameric enolase from Bacillus subtilis. AB - Purified enolase from Bacillus subtilis has a native mass of approximately 370 kDa. Since B. subtilis enolase was found to have a subunit mass of 46.58 kDa, the quaternary structure of B. subtilis is octameric. The pl for B. subtilis enolase is 6.1, the pH optimum (pHo) for activity is 8.1-8.2, and the Km for 2-PGA is approximately 0.67 mM. Using the dimeric Calpha structure of yeast dimeric enolase as a guide, these dimers were arranged as a tetramer of dimers to simulate the electron microscopy image processing obtained for the octameric enolase purified from Thermotoga maritima. This arrangement allowed identification of helix J of one dimer (residues 86-96) and the loop between helix L and strand 1 (HL-S1 loop) of another dimer as possible subunit interaction regions. Alignment of available enolase amino acid sequences revealed that in 16 there are two tandem glycines at the C-terminal end of helix L and the HL-S1 loop is truncated by 4-6 residues relative to the yeast polypeptide, two structural features absent in enolases known to be dimers. From these arrangements and alignments it is proposed that the GG tandem at the C-terminal end of helix L and truncation of the HL-S1 loop may play a critical role in octamer formation of enolases. Interestingly, the sequence features associated with dimeric quaternary structure are found in three phylogenetically disparate groups, suggesting that the ancestral enolase was an octamer and that the dimeric structure has arisen independently multiple times through evolutionary history. PMID- 9988533 TI - A computer program to compare sequence fingerprints of homologous proteins for the rapid assessment of their primary structure differences. AB - We have developed a computer program for the rapid assessment of the primary structure differences between a protein of unknown sequence and a homologous known protein. Both proteins are reduced, alkylated, and digested with the same hydrolytic agent. The unfractionated peptide mixtures are submitted to automatic sequence analysis. Based on the knowledge of the reference sequence, the program utilizes the analysis data to identify all the potential peptides present in the two mixtures, determining their primary structure, homology degree, and molecular weight calculated both as integer MH+ and average mass variables. These fingerprints allow the user to easily identify the structural differences between the two proteins and clarify possible doubts by a mass spectrometric analysis of the two mixtures. In order to verify the utility of the program, we provide an application example using the already reported data of two homologous proteins. PMID- 9988535 TI - Anaesthetic Research Society. Dundee, July 9-10, 1998. Abstracts. PMID- 9988534 TI - Cell differentiation. Cell multiplication. Web alert. PMID- 9988536 TI - Intensive Care Society and Riverside Group State of the Art Meeting. London, December 11-12, 1997. Abstracts. PMID- 9988537 TI - The effects of oral liarozole on epidermal proliferation and differentiation in severe plaque psoriasis are comparable with those of acitretin. AB - The imidazole derivative liarozole is a potent inhibitor of cytochrome P450 dependent 4-hydroxylation of endogenous all-trans retinoic acid, thereby increasing the levels of all-trans retinoic acid in both plasma and skin. As part of a large, double-blind, randomized clinical study, we investigated the cell biological alterations in uninvolved and lesional skin of 20 patients with severe plaque psoriasis, who were treated with either liarozole or acitretin. The extent and severity of the skin lesions, as recorded by the Psoriasis Area and Severity Index score, was significantly reduced (P TTP. Although ATP could competitively inhibit dCTP uptake with a Ki value of 8 microM, the reconstituted dCTP uptake activity was not sensitive to the ATP/ADP carrier inhibitor atractyloside or the sulfhydryl reagent N-ethylmaleimide. This suggests that the dCTP transport system studied is not the same as the ATP/ADP carrier. In conclusion, these studies describe the first functionally reconstituted mitochondrial carrier that displays an efficient transport activity for dCTP. PMID- 9988698 TI - Sphingosine 1-phosphate-induced cell rounding and neurite retraction are mediated by the G protein-coupled receptor H218. AB - Sphingosine 1-phosphate (SPP) is a lipid second messenger that also acts as a first messenger through the G protein-coupled receptor Edg-1. Here we show that SPP also binds to the related receptors H218 and Edg-3 with high affinity and specificity. SPP and sphinganine 1-phosphate bind to these receptors, whereas neither sphingosylphosphorylcholine nor lysophosphatidic acid compete with SPP for binding to either receptor. Transfection of HEK293 cells with H218 or edg-3, but not edg-1, induces rounded cell morphology in the presence of serum, which contains high levels of SPP. SPP treatment of cells overexpressing H218 cultured in delipidated serum causes cell rounding. A similar but less dramatic effect was observed in cells overexpressing Edg-3 but not with Edg-1. Cell rounding was correlated with apoptotic cell death, probably as a result of loss of attachment. Nerve growth factor-induced neuritogenesis in PC12 cells was inhibited by overexpression of H218 and to a lesser extent Edg-3. SPP treatment rapidly enhanced neurite retraction in PC12 cells overexpressing Edg-1, Edg-3, or H218. Thus, H218, and possibly Edg-3, may be the cell surface receptors responsible for cell rounding and neurite retraction induced by SPP. Moreover, the identification of these two additional SPP receptors indicates that a family of highly specific receptors exists that mediate different responses to SPP. PMID- 9988699 TI - A new model of dual interacting ligand binding sites on integrin alphaIIbbeta3. AB - The platelet integrin alphaIIbbeta3 mediates platelet aggregation and platelet adhesion. This integrin is the key to hemostasis and also to pathologic vascular occlusion. A key domain on alphaIIbbeta3 is the ligand binding site, which can bind to plasma fibrinogen and to a number of Arg-Gly-Asp (RGD)-type ligands. However, the nature and function of the ligand binding pocket on alphaIIbbeta3 remains controversial. Some studies suggest the presence of two ligand binding pockets, whereas other reports indicate a single binding pocket. Here we use surface plasmon resonance to show that alphaIIbbeta3 contains two distinct ligand binding pockets. One site binds to fibrinogen, and a separate site binds to RGD type ligands. More importantly, however, the two ligand binding pockets are interactive. RGD-type ligands are capable of binding to alphaIIbbeta3 even when it is already occupied by fibrinogen. Once bound, RGD-type ligands induce the dissociation of fibrinogen from alphaIIbbeta3. This allosteric cross-talk has important implications for anti-platelet therapy because it suggests a novel approach for the dissolution of existing platelet thrombi. PMID- 9988700 TI - Calreticulin enhances the transcriptional activity of thyroid transcription factor-1 by binding to its homeodomain. AB - Transcription factors are often regulated by associated protein cofactors that are able to modify their activity by several different mechanisms. In this study we show that calreticulin, a Ca2+-binding protein with chaperone activity, binds to thyroid transcription factor-1 (TTF-1), a homeodomain-containing protein implicated in the differentiation of lung and thyroid. The interaction between calreticulin and TTF-1 appears to have functional significance because it results in increased transcriptional stimulation of TTF-1-dependent promoters. Calreticulin binds to the TTF-1 homeodomain and promotes its folding, suggesting that the mechanism involved in stimulation of transcriptional activity is an increase of the steady-state concentration of active TTF-1 protein in the cell. We also demonstrate that calreticulin mRNA levels in thyroid cells are under strict control by the thyroid-stimulating hormone, thus implicating calreticulin in the modulation of thyroid gene expression by thyroid-stimulating hormone. PMID- 9988701 TI - Cloning and functional characterization of the 5'-flanking region of the human monocyte chemoattractant protein-1 receptor (CCR2) gene. Essential role of 5' untranslated region in tissue-specific expression. AB - The human monocyte chemoattractant protein-1 receptor designated hCCR2 is an essential co-receptor in cell entry by the human immunodeficiency virus as well as a receptor for monocyte chemoattractant protein-1, a member of the family of C C chemokines that mediate monocyte chemotaxis. To elucidate the molecular mechanisms underlying the transcriptional regulation of hCCR2, we cloned and sequenced the hCCR2 gene; it was approximately 8 kilobase pairs in length and consisted of three exons divided by two introns. In the 5'-flanking region, there were the typical mammalian promoter consensus elements, a CAAT box and a TATA box, resulting in a single transcription initiation site. In addition, we found clustered tissue-specific cis-regulatory elements such as GATA consensus sequences, Oct-1 binding sequences, and CAAT/enhancer-binding protein binding sequences. Luciferase assays with various promoter deletions and gel mobility shift assays indicated that three cis-regulatory elements located within the region from -89 to +118 are required for basal activity in THP-1 cells. One element is an octamer sequence 36-base pair upstream from the TATA box; it binds mainly to Oct-1 and is capable of increasing transcriptional activity. The other two elements, which are tandem recognition sites of the CAAT/enhancer-binding protein family, are located in the 5'-untranslated region and account for the transcriptional activation as well as the tissue specificity of hCCR2. PMID- 9988702 TI - Selective activation of G protein subtypes in the vomeronasal organ upon stimulation with urine-derived compounds. AB - Chemosensory neurons in the vomeronasal organ (VNO) detect pheromones related to social and reproductive behavior in most terrestrial vertebrates. Current evidence indicate that the chemoelectrical transduction process is mediated by G protein-coupled second messenger cascades. In the present study, attempts were made to identify the G protein subtypes which are activated upon stimulation with urinary pheromonal components. G protein-specific antibodies were employed to interfere specifically with inositol 1,3,4-trisphosphate formation induced by urinary stimuli and to immunoprecipitate Galpha-subunits, activation dependently labeled with [alpha-32P]GTP azidoanilide. The results of both experimental approaches indicate that stimulation of female VNO membrane preparations with male urine samples induces activation of Gi as well as Go subtypes. Experiments using different fractions of urine revealed that upon stimulation with lipophilic volatile odorants, only Gi proteins were activated, whereas Go activation was elicited by alpha2u-globulin, a major urinary protein, which is a member of the lipocalin superfamily. Since each G protein subtype is stereotypically coexpressed with one of the two structurally different candidate pheromone receptors (V1R and V2R), the results provide the first experimental evidence that V1Rs coexpressed with Gi may be activated by lipophilic probably volatile odorants, whereas V2Rs coexpressed with Go seem to be specialized to interact with pheromonal components of proteinaceous nature. PMID- 9988703 TI - 1,25-dihydroxyvitamin D3 induces phospholipase D-1 expression in primary mouse epidermal keratinocytes. AB - The hormone 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) elicits the programmed pattern of differentiation in epidermal keratinocytes. Based on data indicating a potential role of phospholipase D (PLD) in mediating keratinocyte differentiation, we investigated the effect of 1,25(OH)2D3 on PLD expression. A 24-h exposure to 1, 25(OH)2D3 stimulated PLD-1, but not PLD-2, mRNA expression. This 1, 25(OH)2D3-enhanced expression was accompanied by increased total PLD and PLD-1 activity. Time course studies indicated that 1,25(OH)2D3 induced PLD-1 expression by 8 h, with a maximal increase at 20-24 h. Exposure to 1,25(OH)2D3 inhibited proliferation over the same time period with similar kinetics. Expression of the early (spinous) differentiation marker keratin 1 decreased in response to 1, 25(OH)2D3 over 12-24 h. Treatment with 1,25(OH)2D3 enhanced the activity of transglutaminase, a late (granular) differentiation marker, by 12 h with a maximal increase after 24 h. In situ hybridization studies demonstrated that the highest levels of PLD-1 expression are in the more differentiated (spinous and granular) layers of the epidermis, with little expression in basal keratinocytes. Our results suggest a role for PLD expression/activity during keratinocyte differentiation. PMID- 9988704 TI - The Saccharomyces cerevisiae FAT1 gene encodes an acyl-CoA synthetase that is required for maintenance of very long chain fatty acid levels. AB - The Saccharomyces cerevisiae FAT1 gene appears to encode an acyl-CoA synthetase that is involved in the regulation of very long chain (C20-C26) fatty acids. Fat1p, has homology to a rat peroxisomal very long chain fatty acyl-CoA synthetase. Very long chain acyl-CoA synthetase activity is reduced in strains containing a disrupted FAT1 gene and is increased when FAT1 is expressed in insect cells under control of a baculovirus promoter. Fat1p accounts for approximately 90% of the C24-specific acyl-CoA synthetase activity in glucose grown cells and approximately 66% of the total activity in cells grown under peroxisomal induction conditions. Localization of functional Fat1p:green fluorescent protein gene fusions and subcellular fractionation of C24 acyl-CoA synthetase activities indicate that the majority of Fat1p is located in internal cellular locations. Disruption of the FAT1 gene results in the accumulation of very long chain fatty acids in the sphingolipid and phospholipid fractions. This includes a 10-fold increase in C24 acids and a 6-fold increase in C22 acids. These abnormal accumulations are further increased by perturbation of very long chain fatty acid synthesis. Overexpression of Elo2p, a component of the fatty acid elongation system, in fat1Delta cells causes C20-C26 levels to rise to approximately 20% of the total fatty acids. These data suggest that Fat1p is involved in the maintenance of cellular very long chain fatty acid levels, apparently by facilitating beta-oxidation of excess intermediate length (C20-C24) species. Although fat1Delta cells were reported to grow poorly in oleic acid supplemented medium when fatty acid synthase activity is inactivated by cerulenin, fatty acid import is not significantly affected in cells containing disrupted alleles of FAT1 and FAS2 (a subunit of fatty acid synthase). These results suggest that the primary cause of the growth-defective phenotype is a failure to metabolize the incorporated fatty acid rather than a defect in fatty acid transport. Certain fatty acyl-CoA synthetase activities, however, do appear to be essential for bulk fatty acid transport in Saccharomyces. Simultaneous disruption of FAA1 and FAA4, which encode long chain (C14-C18) fatty acyl-CoA synthetases, effectively blocks the import of long chain saturated and unsaturated fatty acids. PMID- 9988705 TI - Detailed architecture of the barley chloroplast psbD-psbC blue light-responsive promoter. AB - The photosystem II reaction center chlorophyll protein D2, is encoded by the chloroplast gene psbD. PsbD is transcribed from at least three different promoters, one which is activated by high fluence blue light. Sequences within 130 base pairs (bp) of the psbD blue light-responsive promoter (BLRP) are highly conserved in higher plants. In this study, the structure of the psbD BLRP was analyzed in detail using deletion and site-directed mutagenesis and in vitro transcription. Deletion analysis showed that a 53-bp DNA region of the psbD BLRP, from -57 to -5, was sufficient for transcription in vitro. Mutation of a putative prokaryotic -10 element (TATTCT) located from -7 to -12 inhibited transcription from the psbD BLRP. In contrast, mutation of a putative prokaryotic -35 element, had no influence on transcription. Mutation of a TATATA sequence located between the barley psbA -10 and -35 elements significantly reduced transcription from this promoter. However, site-directed mutation of sequences located between -35 and -10 had no effect on transcription from the psbD BLRP. Transcription from the psbD BLRP was previously shown to require a 22-bp sequence, termed the AAG-box, located between -36 and -57. The AAG-box specifically binds the protein complex AGF. Site-directed mutagenesis identified two different sequence motifs in the AAG-box that are important for transcription in vitro. Based on these results, we propose that positive factors bind to the AAG-box and interact with the chloroplast-encoded RNA polymerase to promote transcription from the psbD BLRP. Transcription from the psbD BLRP is thus similar to type II bacterial promoters that use activating proteins to stimulate transcription. Transcription of the psbD BLRP was approximately 6. 5-fold greater in plastid extracts from illuminated versus dark-grown plants. This suggests that light-induced activation of this promoter in vivo involves factors interacting with the 53-bp psbD BLRP in vitro. PMID- 9988706 TI - Multiple functional Sp1 domains in the minimal promoter region of the neuronal nicotinic receptor alpha5 subunit gene. AB - The alpha5 subunit is a component of the neuronal nicotinic acetylcholine receptors, which are probably involved in the activation step of the catecholamine secretion process in bovine adrenomedullary chromaffin cells. The promoter of the gene coding for this subunit was isolated, and its proximal region was characterized, revealing several GC boxes located close to the site of transcription initiation (from -111 to -40). Deletion analysis and transient transfections showed that a 266-base pair region (-111 to +155) gave rise to approximately 77 and 100% of the maximal transcriptional activity observed in chromaffin and SHSY-5Y neuroblastoma cells, respectively. Site-directed mutagenesis of five different GC motifs indicated that all of them contribute to the activity of the alpha5 gene, but in a different way, depending on the type of transfected cell. Thus, in SHSY-5Y cells, alteration of the most promoter proximal of the GC boxes decreased alpha5 promoter activity by approximately 50%, whereas single mutations of the other GC boxes had no effect. In chromaffin cells, by contrast, modification of any of the GC boxes produced a similar decrease in promoter activity (50-69%). In both cell types, however, activity was almost abolished when four GC boxes were suppressed simultaneously. Electrophoretic mobility shift assays using nuclear extracts from either chromaffin or SHSY-5Y cells showed the specific binding of Sp1 protein to fragment -111 to -27. Binding of Sp1 to the GC boxes was also demonstrated by DNase I footprint analysis. This study suggests that the general transcription factor Sp1 plays a dominant role in alpha5 subunit expression, as has also been demonstrated previously for alpha3 and beta4 subunits. Since these three subunits have their genes tightly clustered and are expressed in chromaffin cells, probably as components of the same receptor subtype, we propose that Sp1 constitutes the key factor of a regulatory mechanism common to the three subunits. PMID- 9988707 TI - Transactivation of the urokinase-type plasminogen activator receptor gene through a novel promoter motif bound with an activator protein-2alpha-related factor. AB - The urokinase receptor overexpressed in invasive cancers promotes laminin degradation. The current study was undertaken to identify cis elements and trans acting factors activating urokinase receptor expression through a footprinted ( 148/-124) region of the promoter containing putative activator protein-2- and Sp1 binding motifs. Mobility shifting experiments using nuclear extract from a high urokinase receptor-expressing cell line (RKO) indicated that Sp1, Sp3, and a factor similar to, but distinct from, activator protein-2alpha bound to this region. Mutations preventing the binding of the activator protein 2alpha-related factor diminished urokinase receptor promoter activity. In RKO cells, the expression of a negative regulator of activator protein-2 function diminished urokinase receptor promoter activity, protein, and laminin degradation. Conversely, urokinase receptor promoter activity in low urokinase receptor expressing GEO cells was increased by activator protein-2alphaA expression. Although using GEO nuclear extract, little activator protein-2alpha-related factor bound to the footprinted region, phorbol 12-myristate 13-acetate treatment, which induces urokinase receptor expression, increased complex formation. Mutations preventing the activator protein-2alpha-related factor and Sp1/Sp3 binding reduced urokinase receptor promoter stimulation by this agent. Thus, the constitutive and phorbol 12-myristate 13-acetate-inducible expression of the urokinase receptor is mediated partly through trans-activation of the promoter via a sequence (-152/-135) bound with an activator protein-2alpha related factor. PMID- 9988708 TI - Distinct "assisted" and "spontaneous" mechanisms for the insertion of polytopic chlorophyll-binding proteins into the thylakoid membrane. AB - The biogenesis of several bacterial polytopic membrane proteins has been shown to require signal recognition particle (SRP) and protein transport machinery, and one such protein, the major light-harvesting chlorophyll-binding protein (LHCP) exhibits these requirements in chloroplasts. In this report we have used in vitro insertion assays to analyze four additional members of the chlorophyll-a/b binding protein family. We show that two members, Lhca1 and Lhcb5, display an absolute requirement for stroma, nucleoside triphosphates, and protein transport apparatus, indicating an "assisted" pathway that probably resembles that of LHCP. Two other members, however, namely an early light-inducible protein 2 (Elip2) and photosystem II subunit S (PsbS), can insert efficiently in the complete absence of SRP, SecA activity, nucleoside triphosphates, or a functional Sec system. The data suggest a possibly spontaneous insertion mechanism that, to date, has been characterized only for simple single-span proteins. Of the membrane proteins whose insertion into thylakoids has been analyzed, five have now been shown to insert by a SRP/Sec-independent mechanism, suggesting that this is a mainstream form of targeting pathway. We also show that PsbS and Elip2 molecules are capable of following either "unassisted" or assisted pathways, and we discuss the implications for the mechanism and role of SRP in chloroplasts. PMID- 9988709 TI - Molecular cloning and characterization of a mitochondrial selenocysteine containing thioredoxin reductase from rat liver. AB - A thioredoxin reductase (TrxR), named here TrxR2, that did not react with antibodies to the previously identified TrxR (now named TrxR1) was purified from rat liver. Like TrxR1, TrxR2 was a dimeric enzyme containing selenocysteine (Secys) as the COOH-terminal penultimate residue. A cDNA encoding TrxR2 was cloned from rat liver; the open reading frame predicts a polypeptide of 526 amino acids with a COOH-terminal Gly-Cys-Secys-Gly motif provided that an in-frame TGA codon encodes Secys. The 3'-untranslated region of the cDNA contains a canonical Secys insertion sequence element. The deduced amino acid sequence of TrxR2 shows 54% identity to that of TrxR1 and contained 36 additional residues upstream of the experimentally determined NH2-terminal sequence. The sequence of this 36 residue region is typical of that of a mitochondrial leader peptide. Immunoblot analysis confirmed that TrxR2 is localized almost exclusively in mitochondria, whereas TrxR1 is a cytosolic protein. Unlike TrxR1, which was expressed at a level of 0.6 to 1.6 microgram/milligram of total soluble protein in all rat tissues examined, TrxR2 was relatively abundant (0.3 to 0.6 microgram/mg) only in liver, kidney, adrenal gland, and heart. The specific localization of TrxR2 in mitochondria, together with the previous identification of mitochondria-specific thioredoxin and thioredoxin-dependent peroxidase, suggest that these three proteins provide a primary line of defense against H2O2 produced by the mitochondrial respiratory chain. PMID- 9988710 TI - Thiolation of the gammaB-crystallins in intact bovine lens exposed to hydrogen peroxide. AB - Oxidative damage of the lens causes disulfide bonds between cysteinyl residues of lens proteins and thiols such as glutathione and cysteine, which may lead to cataract. The effect of H2O2 oxidation was determined by comparing bovine lenses incubated with and without 30 mM H2O2. The H2O2 treatment decreased the glutathione and increased the protein-glutathione and protein-cysteine disulfides in the lens. The molecular mass of the gammaB-crystallin isolated from lenses, not treated with H2O2, agreed with the published sequence (Mr 20,966). Some lenses also had a less abundant gammaB-crystallin component 305 Da higher (Mr 21,270), suggesting the presence of a glutathione adduct. The gammaB-crystallins from H2O2 treated lenses had three components, the major one with one GSH adduct, another one with the mass of unmodified gammaB-crystallin, and a third with a mass consistent with addition of two GSH adducts. Mass spectrometric analysis of tryptic peptides of gammaB-crystallins from different lenses indicated that the +305 Da modifications were not at a specific cysteine. For the lenses incubated without H2O2, there was evidence of adducts at Cys-41 and in peptide 10-31, which includes 3 cysteines. Analysis of modified peptide 10-31 by tandem mass spectrometry showed GSH adducts at Cys-15, Cys-18, and Cys-22. In addition, gammaB-crystallins from H2O2-treated lenses had an adduct at Cys-109, partial oxidation at all 7 Met residues, and evidence for two disulfide bonds. PMID- 9988711 TI - Inhibition of DNA synthesis by a farnesyltransferase inhibitor involves inhibition of the p70(s6k) pathway. AB - Previously, the protein farnesyltransferase inhibitor (FTI), L-744, 832, has been shown to inhibit the proliferation of a number of tumor cell lines in vitro in a manner that correlated with the inhibition of the mitogen-activated protein kinase cascade. Here we show that FTI inhibits p70(s6k) phosphorylation in mammary tumors in vivo in transgenic mice. Furthermore, in a mouse keratinocyte cell line, FTI inhibits p70(s6k) phosphorylation and activity and inhibits PHAS-1 phosphorylation in vitro in both rapidly growing cells and in growth factor stimulated quiescent cells. Dominant-negative Ras expression inhibits p70(s6k) stimulation by epidermal growth factor, demonstrating a requirement for Ras activity during p70(s6k) activation. FTI does not inhibit protein kinase B phosphorylation on Ser473, indicating that FTI does not act by inhibiting phosphatidylinositol 3-kinase. FTI also inhibits DNA synthesis in keratinocytes, and inhibition of DNA synthesis correlates closely with p70(s6k) inhibition. Rapamycin, an inhibitor of p70(s6k) and PHAS-1 phosphorylation, causes a 30-45% reduction in DNA synthesis in keratinocytes, while FTI induces an 80-90% reduction in DNA synthesis. These observations suggest that alteration of p70(s6k) and PHAS-1 function by FTI are responsible for a substantial portion of the growth-inhibitory properties of FTI. Together, these data demonstrate that p70(s6k) and PHAS-1 are novel downstream targets of FTI and suggest that the anti tumor properties of FTI are probably due to the inhibition of multiple mitogenic pathways. PMID- 9988712 TI - Serotonin 5-HT1A receptor-mediated Erk activation requires calcium/calmodulin dependent receptor endocytosis. AB - Many receptors that couple to heterotrimeric guanine nucleotide-binding (G) proteins mediate rapid activation of the mitogen-activated protein kinases, Erk1 and Erk2. The Gi-coupled serotonin (5-hydroxytryptamine (5-HT)) 5-HT1A receptor, heterologously expressed in Chinese hamster ovary or human embryonic kidney 293 cells, mediated rapid activation of Erk1/2 via a mechanism dependent upon both Ras activation and clathrin-mediated endocytosis. This activation was attenuated by chelation of intracellular Ca2+ and Ca2+/calmodulin (CAM) inhibitors or the CAM sequestrant protein calspermin. The CAM-dependent step in the Erk1/2 activation cascade is downstream of Ras activation, because inhibitors of CAM antagonize Erk1/2 activation induced by constitutively activated mutants of Ras and c-Src but not by constitutively activated mutants of Raf and MEK (mitogen and extracellular signal-regulated kinase). Inhibitors of the classical CAM effectors myosin light chain kinase, CAM-dependent protein kinases II and IV, PP2B, and CAM sensitive phosphodiesterase had no effect upon 5-HT1A receptor-mediated Erk1/2 activation. Because clathrin-mediated endocytosis was required for 5-HT1A receptor-mediated Erk1/2 activation, we postulated a role for CAM in receptor endocytosis. Inhibition of receptor endocytosis by use of sequestration-defective mutants of beta-arrestin1 and dynamin attenuated 5-HT1A receptor-stimulated Erk1/2 activation. Inhibition of CAM prevented agonist-dependent endocytosis of epitope-tagged 5-HT1A receptors. We conclude that CAM-dependent activation of Erk1/2 through the 5-HT1A receptor reflects its role in endocytosis of the receptor, which is a required step in the activation of MEK and subsequently Erk1/2. PMID- 9988713 TI - The Bacillus stearothermophilus mannitol regulator, MtlR, of the phosphotransferase system. A DNA-binding protein, regulated by HPr and iicbmtl dependent phosphorylation. AB - D-Mannitol is taken up by Bacillus stearothermophilus and phosphorylated via a phosphoenolpyruvate-dependent phosphotransferase system (PTS). The genes involved in the mannitol uptake were recently cloned and sequenced. One of the genes codes for a putative transcriptional regulator, MtlR. The presence of a DNA binding helix-turn-helix motif and two antiterminator-like PTS regulation domains, suggest that MtlR is a DNA-binding protein, the activity of which can be regulated by phosphorylation by components of the PTS. To demonstrate DNA binding of MtlR to a region upstream of the mannitol promoter, by DNA footprinting, MtlR was overproduced and purified. EI, HPr, IIAmtl, and IICBmtl of B. stearothermophilus were purified and used to demonstrate that MtlR can be phosphorylated and regulated by HPr and IICBmtl, in vitro. Phosphorylation of MtlR by HPr increases the affinity of MtlR for its binding site, whereas phosphorylation by IICBmtl results in a reduction of this affinity. The differential effect of phosphorylation, by two different proteins, on the DNA binding properties of a bacterial transcriptional regulator has not, to our knowledge, been described before. Regulation of MtlR by two components of the PTS is an example of an elegant control system sensing both the presence of mannitol and the need to utilize this substrate. PMID- 9988714 TI - Transfection of an active cytochrome P450 arachidonic acid epoxygenase indicates that 14,15-epoxyeicosatrienoic acid functions as an intracellular second messenger in response to epidermal growth factor. AB - A common feature of most isolated cell systems is low or undetectable levels of bioactive cytochrome P450. We therefore developed stable transfectants of the renal epithelial cell line, LLCPKcl4, that expressed an active regio- and enantioselective arachidonic acid (AA) epoxygenase. Site-specific mutagenesis was used to convert bacterial P450 BM-3 into an active regio- and stereoselective 14S,15R-epoxygenase (F87V BM-3). In clones expressing F87V BM-3 (F87V BM-3 cells), exogenous AA induced significant 14S,15R-epoxyeicosatrienoic acid (EET) production (241. 82 ng/10(8) cells, >97% of total EETs), whereas no detectable EETs were seen in cells transfected with vector alone. In F87V BM-3 cells, AA stimulated [3H]thymidine incorporation and increased cell proliferation, which was blocked by the tyrosine kinase inhibitor, genistein, by the phosphatidylinositol 3 (PI-3) kinase inhibitors, wortmannin and LY294002, and by the mitogen-activated protein kinase kinase inhibitor, PD98059. AA also induced tyrosine phosphorylation of extracellular signal-regulated kinase (ERK) and PI-3 kinase that was inhibited by the cytochrome P450 BM-3 inhibitor, 17-ODYA. Epidermal growth factor (EGF) increased EET production in F87V BM-3 cells, which was completely abolished by pretreatment with either 17-ODYA or the phospholipase A2 (PLA2) inhibitor, quinacrine. Compared with vector-transfected cells, F87 BM-3 transfected cells demonstrated marked increases in both the extent and sensitivity of DNA synthesis in response to EGF. These changes occurred in the absence of significant differences in EGF receptor expression. As seen with exogenous AA, EGF increased ERK tyrosine phosphorylation to a significantly greater extent in F87V BM-3 cells than in vector-transfected cells. Furthermore, in these control cells, neither 17-ODYA nor quinacrine inhibited EGF-induced ERK tyrosine phosphorylation. On the other hand, in F87V BM-3 cells, both inhibitors reduced ERK tyrosine phosphorylation to levels indistinguishable from that seen in cells transfected with vector alone. These studies provide the first unequivocal evidence for a role for the AA epoxygenase pathway and endogenous EET synthesis in EGF-mediated signaling and mitogenesis and provide compelling evidence for the PLA2-AA-EET pathway as an important intracellular-signaling pathway in cells expressing high levels of cytochrome P450 epoxygenase. PMID- 9988715 TI - Heat-induced conformational changes of Ara h 1, a major peanut allergen, do not affect its allergenic properties. AB - Ara h 1, a major peanut allergen was isolated, and its structure on secondary, tertiary, and quaternary level at ambient temperature was investigated using spectroscopic and biochemical techniques. Ara h 1 appeared to be a highly structured protein on a secondary level, possesses a clear tertiary fold, and is present as a trimeric complex. Heat treatment of purified Ara h 1 results in an endothermic, irreversible transition between 80 and 90 degreesC, leading to an increase in beta-structures and a concomitant aggregation of the protein. Ara h 1 from peanuts that were heat-treated prior to the purification procedure exhibited a similar denatured state with an increased secondary folding and a decreased solubility. The effect of heat treatment on the in vitro allergenic properties of Ara h 1 was investigated by means of a fluid-phase IgE binding assay using serum from patients with a clinically proven peanut allergy. Ara h 1 purified from peanuts heated at different temperatures exhibited IgE binding properties similar to those found for native Ara h 1, indicating that the allergenicity of Ara h 1 is heat-stable. We conclude that the allergenicity of Ara h 1 is unaffected by heating, although native Ara h 1 undergoes a significant heat-induced denaturation on a molecular level, indicating that the recognition of conformational epitopes of Ara h 1 by IgE either is not a dominant mechanism or is restricted to parts of the protein that are not sensitive to heat denaturation. PMID- 9988716 TI - Structurally related peptide agonist, partial agonist, and antagonist occupy a similar binding pocket within the cholecystokinin receptor. Rapid analysis using fluorescent photoaffinity labeling probes and capillary electrophoresis. AB - The molecular basis of ligand binding to receptors provides important insights for drug development. Here, we explore domains of the cholecystokinin (CCK) receptor that are critical for ligand binding, using a novel series of fluorescent photolabile probes, receptor proteolysis, and rapid high resolution separation of peptide fragments by capillary electrophoresis. Each probe incorporated the same fluorophore and a photolabile p-benzoylphenylalanine at the amino terminus of the pharmacophoric domain (residue 24 of CCK-33) of CCK analogues representing full agonist, partial agonist, and antagonist of this receptor. Each was used to label the CCK receptor expressed on Chinese hamster ovary-CCKR cells, with the labeled domain then released by cyanogen bromide cleavage. Capillary electrophoresis with laser-induced fluorescence detection achieved an on-capillary mass sensitivity of 1.6 attomoles (10(-18) mol), with an excellent signal-to-noise ratio. Each of the biologically divergent, but structurally similar probes saturably and specifically labeled the same receptor domain, consistent with conservation of "docking" determinants. This had an apparent mass of 2.9 kDa, most consistent with the first extracellular loop domain. An additional probe having its site of covalent attachment in a different region of the probe (residue 29 of CCK-33) labeled a distinct receptor fragment with differential migration on capillary electrophoresis (third extracellular loop). Identification of the specific receptor residue(s) covalently linked to the amino-terminal probes must await further fragmentation and sequence analysis. PMID- 9988717 TI - Characterization of a two-component system in Streptococcus pyogenes which is involved in regulation of hyaluronic acid production. AB - Hyaluronic acid production by group A streptococci is regulated by transcriptional control. In this study, transposon mutagenesis of an unencapsulated strain yielded an encapsulated mutant. Two genes homologous to sensors and response regulators of bacterial two-component systems were identified downstream of the transposon insertion. Inactivation of the putative sensor gene, csrS, in three different unencapsulated strains yielded encapsulated mutant strains. Electrophoretic mobility shift assays determined factor(s) in a cytoplasmic extract of an unencapsulated group A streptococcal strain was binding to a double-stranded DNA fragment derived from the has operon promoter. In contrast, similarly prepared cytoplasmic extracts from a csrS deletion mutant did not shift the fragment. The putative response regulator, CsrR, was partially purified and was shown to bind the has operon promoter fragment. The affinity and specificity of CsrR for the fragment were increased significantly after incubation with acetyl phosphate. DNase I footprinting determined that the acetyl phosphate-treated CsrR was binding to key sequences in the promoter and the coding region of hasA. Therefore, a two-component system is repressing the production of hyaluronic acid in group A streptococci using a phosphorylation dependent binding interaction between the response regulator CsrR and the promoter region of the has operon. PMID- 9988718 TI - Role of interferon regulatory factor-1 and mitogen-activated protein kinase pathways in the induction of nitric oxide synthase-2 in retinal pigmented epithelial cells. AB - Bovine retinal pigmented epithelial cells express an inducible nitric oxide synthase (NOS-2) after activation with interferon-gamma (IFN-gamma) and lipopolysaccharide (LPS). Experiments were performed to investigate the involvement of interferon regulatory factor-1 (IRF-1) on NOS-2 induction and its regulation by NOS-2 inhibitors such as pyrrolidine dithiocarbamate (PDTC), an antioxidant, or protein kinase inhibitors. Analysis by transitory transfections showed that LPS, alone or with IFN-gamma, stimulated activity of the murine NOS-2 promoter fragment linked upstream of luciferase and its suppression by PDTC and by the different protein kinase inhibitors, genistein (tyrosine kinase inhibitor), PD98059 (mitogen-actived protein (MAP) kinase kinase inhibitor), and SB 203580 (p38 MAP inhibitor). Using specific antibodies, we have confirmed that extracellular signal-regulated kinases and p38 MAP kinase were activated by LPS and IFN-gamma in retinal pigmented epithelial cells. Analysis by reverse transcriptase-polymerase chain reaction, Western blot, and electrophoretic mobility shift assay demonstrated that IFN-gamma alone or combined with LPS induced an accumulation of IRF-1 mRNA and protein and IRF-1 DNA binding. Transfections assays with the IRF-1 promoter showed an induction of this promoter with IFN-gamma, potentiated by LPS. The decrease of LPS/IFN-gamma-induced IRF-1 promoter activity, IRF-1 synthesis, and IRF-1 activation, by PDTC, genistein, PD98059, and SB 203580, could explained in part the inhibition of the NOS-2 induction by these compounds. Our results demonstrate that IRF-1 is necessary for NOS-2 induction by LPS and IFN-gamma and that its synthesis requires the involvement of a redox-sensitive step, the activation of tyrosine kinases, and extracellular signal-regulated kinases 1/2 and p38 MAP kinases. PMID- 9988719 TI - Involvement of double-stranded RNA-activated protein kinase in the synergistic activation of nuclear factor-kappaB by tumor necrosis factor-alpha and gamma interferon in preneuronal cells. AB - Tumor necrosis factor-alpha (TNF-alpha) and gamma-interferon (IFN-gamma) cooperate during a variety of biological responses and ultimately synergistically enhance the expression of genes involved in immune and inflammatory responses. Recently, we demonstrated that IFN-gamma can significantly potentiate TNF-alpha induced nuclear factor (NF)-kappaB nuclear translocation in neuronal derived and endothelial cell lines. The mechanism by which these two cytokines exert their synergistic effect on NF-kappaB involves the de novo degradation of the NF-kappaB inhibitor, IkappaBbeta. The double-stranded RNA-dependent kinase PKR is IFN inducible and has been implicated in the activation of NF-kappaB; therefore, we examined the possibility that PKR may play a role in the synergistic activation of NF-kappaB during TNF-alpha/IFN-gamma cotreatment. The PKR inhibitor 2 aminopurine (2-AP) inhibited TNF-alpha/IFN-gamma-induced NF-kappaB nuclear translocation in neuronal derived cells but not in endothelial cells. The induced degradation of IkappaBbeta, which is normally observed upon TNF-alpha/IFN-gamma cotreatment, was blocked completely by 2-AP in neuronal derived cells. Also, 2-AP treatment or overexpression of a catalytically inactive PKR inhibited the TNF alpha/IFN-gamma-induced synergistic activation of kappaB-dependent gene expression. Our results suggest that the signal generated by IFN-gamma during TNF alpha/IFN-gamma cotreatment may require PKR to elicit enhanced NF-kappaB activity, and this signal may affect the stability of the IkappaBbeta protein. PMID- 9988720 TI - Functional regulation of Galpha16 by protein kinase C. AB - Recent evidence demonstrates that the alpha subunits of some heterotrimeric GTP binding proteins (G proteins) are subject to modification by protein kinase C (PKC). For the family of G proteins that activate the phospholipase C/inositol trisphosphate/calcium/PKC pathway, such modification could result in G protein autoregulation. To examine the potential regulation of members of the Galphaq family by PKC phosphorylation, we expressed the thyrotropin-releasing hormone (TRH) receptor in combination with Galphaq, Galpha11, Galpha14, Galpha15, or Galpha16 in Xenopus oocytes and examined the regulation of signaling by PKC activators and inhibitors. For Galpha16 and Galpha15, the two family members of hematopoietic lineage, PKC activators reduce both the magnitude and the time course of TRH-mediated responses; PKC inhibitors have the opposite effect. The PKC-mediated effects are evident in measurements of GTPase activity, suggesting that the regulation is occurring early in the signaling pathway. In vivo phosphorylation experiments demonstrate that Galpha16 is a substrate for PKC modification. By comparison, Galphaq is not phosphorylated by PKC in vivo, and oocytes expressing Galphaq are not functionally modulated by PKC. Repeated TRH stimulation of oocytes expressing Galpha16 mimics the effects of PKC activators, and this functional regulation is correlated with an increase in Galpha16 phosphorylation. A mutant Galpha16 with four consensus PKC phosphorylation sites removed is not phosphorylated in vivo, and TRH responses mediated through the mutant are not regulated by PKC. These results demonstrate that signaling involving hematopoietic G proteins is subject to PKC-mediated autoregulation, at least in part, by phosphorylation of the G protein alpha subunit. PMID- 9988721 TI - Apolipoprotein E containing high density lipoprotein stimulates endothelial production of heparan sulfate rich in biologically active heparin-like domains. A potential mechanism for the anti-atherogenic actions of vascular apolipoprotein e. AB - Reduced heparin and heparan sulfate (HS) proteoglycans (PG) have been observed in both inflammation and atherosclerosis. Methods to increase endogenous heparin and heparan sulfate are not known. We found that incubation of endothelial cells with 500-1,000 micrograms/ml high density lipoprotein (HDL) increased 35SO4 incorporation into PG by 1.5-2.5-fold. A major portion of this increase was in HS and was the result of increased synthesis. Total PG core proteins were not altered by HDL; however, the ratio of 35SO4 to [3H]glucosamine was increased by HDL, suggesting increased sulfation of glycosaminoglycans. In addition, HDL increased the amount of highly sulfated heparin-like HS in the subendothelial matrix. HS from HDL-treated cells bound 40 +/- 5% more 125I-antithrombin III (requires 3-O sulfated HS) and 49 +/- 3% fewer monocytes. Moreover, the HS isolated from HDL-treated cells inhibited smooth muscle cell proliferation (by 83 +/- 5%) better than control HS (56 +/- 6%) and heparin (42 +/- 6%). HDL isolated from apolipoprotein E (apoE)-null mice did not stimulate HS production unless apoE was added. ApoE also stimulated HS production in the absence of HDL. ApoE did not increase 35SO4 incorporation in macrophages and fibroblasts, suggesting that this is an endothelial cell-specific process. Receptor-associated protein inhibited apoE-mediated stimulation of HS only at higher (20 micrograms/ml) doses, suggesting the involvement of a receptor-associated protein-sensitive pathway in mediating apoE actions. In summary, our data identify a novel mechanism by which apoE and apoE-containing HDL can be anti-atherogenic. Identification of specific apoE peptides that stimulate endothelial heparin/HS production may have important therapeutic applications. PMID- 9988722 TI - Adenophostin A and inositol 1,4,5-trisphosphate differentially activate Cl- currents in Xenopus oocytes because of disparate Ca2+ release kinetics. AB - Depletion of endoplasmic reticulum Ca2+ stores induces Ca2+ entry from the extracellular space by a process termed "store-operated Ca2+ entry" (SOCE). It has been suggested that the novel fungal metabolite adenophostin-A may be able to stimulate Ca2+ entry without stimulating Ca2+ release from stores. To test this idea further, we compared Ca2+ release, SOCE, and the stimulation of Ca2+ activated Cl- currents in Xenopus oocytes in response to inositol 1,4,5 trisphosphate (IP3) and adenophostin-A injection. IP3 stimulated an outward Cl- current, ICl1-S, in response to Ca2+ release from stores followed by an inward current, ICl2, in response to SOCE. In contrast, low concentrations of adenophostins (AdAs) activated ICl2 without activating ICl1-S, consistent with the suggestion that AdA can activate Ca2+ entry without stimulating Ca2+ release. However, when Ca2+ entry has been stimulated by AdA, Ca2+ stores are largely depleted of Ca2+, as assessed by the inability of ionomycin to release additional Ca2+. The Ca2+ release stimulated by AdA, however, was 7 times slower than the release stimulated by IP3, which could explain the minimal activation of ICl1-S; when Ca2+ is released slowly, the threshold level required for ICl1-S activation is not attained. PMID- 9988723 TI - Parathyroid hormone-related protein interacts with RNA. AB - Parathyroid hormone-related protein (PTHrP) is a secreted protein that acts as an autocrine and paracrine mediator of cell proliferation and differentiation. In addition to its biological activity that is mediated through signal transduction cascades, there is evidence for an intracellular role for PTHrP in cell cycle progression and apoptosis. These effects are mediated through a mid-region nuclear targeting sequence (NTS) that localizes PTHrP to the region of the nucleolus where ribonucleoprotein complexes form in vivo. In this work, we show that endogenous, transfected, and in vitro translated PTHrP proteins bind homopolymeric and total cellular RNAs at salt concentrations up to 1 M. A peptide representing the PTHrP NTS was effective in competing with the wild-type protein for RNA binding, whereas a similar peptide representing the nucleolin NTS was not. Site-directed mutagenesis revealed that the binding of PTHrP to RNA was direct and was dependent on preservation of a core GXKKXXK motif, embedded in the PTHrP NTS, which is shared with other RNA-binding proteins. The current observations are the first to document RNA binding by a secreted cellular protein and predict a role for PTHrP in regulating RNA metabolism that may be related to its localization in the nucleolus of cells in vivo. PMID- 9988724 TI - Identification of inhibitor specificity determinants in a mammalian phosphodiesterase. AB - Mammalian phosphodiesterase types 3 and 4 (PDE3 and PDE4) hydrolyze cAMP and are essential for the regulation of this intracellular second messenger in many cell types. Whereas these enzymes share structural and biochemical similarities, each can be distinguished by its sensitivity to isozyme-specific inhibitors. By using a series of chimeric enzymes, we have localized the region of PDE4 that confers sensitivity to selective inhibitors. This inhibitor specificity domain lies within a short sequence at the carboxyl terminus of the catalytic domain of the protein, consistent with the competitive nature of inhibition by these compounds. Surprisingly, the identified region also includes some of the most highly conserved residues among PDE isoforms. A yeast-based expression system was used for the isolation and characterization of mutations within this area that confer resistance to the PDE4-specific inhibitor rolipram. Analysis of these mutants indicated that both conserved and unique residues are required for isoform specific inhibitor sensitivity. In some cases, combined point mutations contribute synergistically to the reduction of sensitivity (suppression of IC50). We also report that several mutations display differential sensitivity changes with respect to distinct structural classes of inhibitors. PMID- 9988725 TI - Nickel-catalyzed N-terminal oxidative deamination in peptides containing histidine at position 2 coupled with sulfite oxidation. AB - Peptides containing histidine at position 2 were observed to undergo spontaneous N-terminal oxidative deamination in aqueous solution in the presence of Ni(II), sulfite, and ambient oxygen. The reaction resulted in the formation of a free carbonyl on the N-terminal alpha-carbon (alpha-ketoamide) and was catalytic with respect to nickel. This oxidative deamination was confirmed by 13C NMR, 1H NMR, mass spectrometry, and chemical tests. No evidence of modification of histidine was found. It was demonstrated that the nickel-dependent N-terminal oxidative deamination also occurred in His-2 peptides using potassium peroxymonosulfate (oxone) as an oxidant. When oxone was used, oxygen was not required for the deamination to proceed. The results suggest that both nickel-catalyzed reactions (sulfite and oxygen, and oxone) produce an imine intermediate that spontaneously hydrolyzes to form the free carbonyl. These findings may provide a physiologically relevant model for oxidative carbonyl formation in vivo, as well as a useful method for producing a site-specific carbonyl on peptides and proteins. PMID- 9988726 TI - Role of the intronic elements in the endogenous immunoglobulin heavy chain locus. Either the matrix attachment regions or the core enhancer is sufficient to maintain expression. AB - High level expression in mice of transgenes derived from the immunoglobulin heavy chain (IgH) locus requires both the core enhancer (Emu) and the matrix attachment regions (MARs) that flank Emu. The need for both elements implies that they each perform a different function in transcription. While it is generally assumed that expression of the endogenous IgH locus has similar requirements, it has been difficult to assess the role of these elements in expression of the endogenous heavy chain gene, because B cell development and IgH expression are strongly interdependent and also because the locus contains other redundant activating elements. We have previously described a gene-targeting approach in hybridoma cells that overcomes the redundancy problem to yield a stable cell line in which expression of the IgH locus depends strongly on elements in the MAR-Emu-MAR segment. Using this system, we have found that expression of the endogenous mu gene persists at substantially (approximately 50%) normal levels in recombinants which retain either the MARs or Emu. That is, despite the dissimilar biochemical activities of these two elements, either one is sufficient to maintain high level expression of the endogenous locus. These findings suggest new models for how the enhancer and MARs might collaborate in the initiation or maintenance of transcription. PMID- 9988727 TI - Post-translation control of Nramp metal transport in yeast. Role of metal ions and the BSD2 gene. AB - The Saccharomyces cerevisiae SMF1 gene encodes a member of the well conserved family of Nramp metal transport proteins. Previously, we determined that heavy metal uptake by Smf1p was down-regulated by the product of the S. cerevisiae BSD2 gene. We now demonstrate that this regulation occurs at the level of protein stability. In wild type strains, the bulk of Smf1p is normally directed to the vacuole and is rapidly degraded by vacuolar proteases in a PEP4-dependent manner. In bsd2Delta mutants, Smf1p fails to enter the vacuole, and the Nramp protein is stabilized. Metal ions themselves play an important role in the post translational regulation of Smf1p. The depletion of heavy metals from the growth medium effects stabilization of Smf1p and additionally results in accumulation of this transporter at the cell surface. Supplementation of manganese alone is sufficient to trigger rapid degradation of Smf1p in a Bsd2p-dependent manner. Together the action of Bsd2p and metal ions provide a rapid and effective means for controlling Nramp metal transport in response to environmental changes. PMID- 9988728 TI - Mutations in ribosomal protein L10e confer resistance to the fungal-specific eukaryotic elongation factor 2 inhibitor sordarin. AB - The natural product sordarin, a tetracyclic diterpene glycoside, selectively inhibits fungal protein synthesis by impairing the function of eukaryotic elongation factor 2 (eEF2). Sordarin and its derivatives bind to the eEF2 ribosome-nucleotide complex in sensitive fungi, stabilizing the post translocational GDP form. We have previously described a class of Saccharomyces cerevisiae mutants that exhibit resistance to varying levels of sordarin and have identified amino acid substitutions in yeast eEF2 that confer sordarin resistance. We now report on a second class of sordarin-resistant mutants. Biochemical and molecular genetic analysis of these mutants demonstrates that sordarin resistance is dependent on the essential large ribosomal subunit protein L10e in S. cerevisiae. Five unique L10e alleles were characterized and sequenced, and several nucleotide changes that differ from the wild-type sequence were identified. Changes that result in the resistance phenotype map to 4 amino acid substitutions and 1 amino acid deletion clustered in a conserved 10-amino acid region of L10e. Like the previously identified eEF2 mutations, the mutant ribosomes show reduced sordarin-conferred stabilization of the eEF2-nucleotide ribosome complex. To our knowledge, this report provides the first description of ribosomal protein mutations affecting translocation. These results and our previous observations with eEF2 suggest a functional linkage between L10e and eEF2. PMID- 9988729 TI - Which form of dopamine is the substrate for the human dopamine transporter: the cationic or the uncharged species? AB - The question of which is the active form of dopamine for the neuronal dopamine transporter is addressed in HEK-293 cells expressing the human dopamine transporter. The Km value for [3H]dopamine uptake fell sharply when the pH was increased from 6.0 to 7.4 and then changed less between pH 7.4 and 8.2. The KI for dopamine in inhibiting the cocaine analog [3H]2beta-carbomethoxy-3beta-(4 fluorophenyl)tropane binding displayed an identical pH dependence, suggesting that changes in uptake result from changes in dopamine recognition. Dopamine can exist in the anionic, neutral, cationic, or zwitterionic form, and the contribution of each form was calculated. The contribution of the anion is extremely low (3 and alpha2-->8 sialyl linkages being susceptible. The major subcellular localization of the expressed sialidase was assessed to be plasma membrane by Percoll density gradient centrifugation of cell homogenates and by immunofluorescence staining of the transfected COS-7 cells. Analysis of the membrane topology by protease protection assay suggested that this sialidase has a type I membrane orientation with its amino terminus facing to the extracytoplasmic side and lacking a signal sequence. PMID- 9988746 TI - Determination and characterization of the hemagglutinin-associated short motifs found in Porphyromonas gingivalis multiple gene products. AB - Porphyromonas gingivalis is a Gram-negative anaerobic bacterial species implicated as an important pathogen in the development of adult periodontitis. In our studies of P. gingivalis and ways to protect against periodontal disease, we have prepared the monoclonal antibody mAb-Pg-vc and its recombinant antibody, which are capable of inhibiting the hemagglutinating activity of P. gingivalis (Shibata, Y., Kurihara, K., Takiguchi, H., and Abiko, Y. (1998) Infect. Immun. 66, 2207-2212). To clarify the antigenically related hemagglutinating domains, we attempted to determine the minimum motifs responsible for P. gingivalis hemagglutinin. Initially, the 9-kilobase EcoRI fragment encoding the 130-kDa protein was cloned from the P. gingivalis chromosome using mAb-Pg-vc. Western blot analysis of nested deletion clones, the competition experiments using synthetic peptides, and the binding assay of the phage-displayed peptides using the mAb-Pg-vc allowed us to identify the minimum motifs, PVQNLT. Furthermore, the presence of multi-gene family coding for this epitope was confirmed via Southern blot analysis and PCR using the primers complementary to the domain corresponding to this epitope. It is suggested that the hemagglutinin-associated motif may be PVQNLT and that the gene families specifying this motif found in P. gingivalis chromosome encode many hemagglutinin and/or hemagglutinin-related proteases. PMID- 9988747 TI - The Ost1p subunit of yeast oligosaccharyl transferase recognizes the peptide glycosylation site sequence, -Asn-X-Ser/Thr-. AB - Other laboratories have established that oligosaccharyl transferase (OST) from Saccharomyces cerevisiae can be purified as a protein complex containing eight different subunits. To identify the OST subunit that recognizes the peptide sites that can be glycosylated, we developed photoaffinity probes containing a photoreactive benzophenone derivative, p-benzoylphenylalanine (Bpa), as part of an 125I-labeled peptide that could be expected to be glycosylated. We found that Asn-Bpa-Thr peptides served as substrates for OST and that photoactivation of these probes in the presence of microsomes abolished the OST activity. Photoactivation of 125I-labeled Asn-Bpa-Thr in the presence of microsomes resulted in specific covalent labeling of a protein doublet of molecular mass 62 and 64 kDa. By carrying out the photoactivation of the probe using microsomes containing epitope-tagged Ost1p, we demonstrated that the 125I-labeled protein was Ost1p. Radiolabeling of this protein was dependent on irradiation at 350 nm. No labeling was detected using a probe containing Ala instead of Thr as the third amino acid residue. We conclude that Ost1p is the subunit of the OST complex that recognizes the peptide sites in the nascent chains that are destined to be glycosylated. PMID- 9988748 TI - The cyclin-dependent kinase inhibitor p27(Kip1) is involved in thyroid hormone mediated neuronal differentiation. AB - The thyroid hormone (triiodothyronine, T3) is essential for normal brain maturation. To determine the mechanisms by which T3 controls neuronal proliferation and differentiation, we have analyzed the effect of this hormone on the expression and activity of cell cycle-regulating molecules in neuroblastoma N2a-beta cells that overexpress the beta1 isoform of the T3 receptor. Our results show that incubation of N2a-beta cells with T3 leads to a rapid down-regulation of the c-myc gene and to a decrease of cyclin D1 levels. T3 also causes a strong and sustained increase of the levels of the cyclin kinase inhibitor p27(Kip1). This increase is secondary, to the augmented levels of p27(Kip1) transcripts as well as to stabilization of the p27(Kip1) protein. The increased levels of p27(Kip1) lead to a significant increase in the amount of p27(Kip1) associated with cyclin-dependent kinase 2 (CDK2), and to a marked inhibition of the kinase activity of the cyclin.CDK2 complexes. As a consequence, the retinoblastoma protein (pRb) and the retinoblastoma protein-related protein p130 are hypophosphorylated in T3-treated N2a-beta cells. This study shows for the first time that T3-mediated growth arrest and neuronal differentiation are associated with an increase in the levels of a cyclin kinase inhibitor, which does not allow the inactivation of retinoblastoma proteins required for progression through the restriction point in the cell cycle. PMID- 9988749 TI - Characterization of a new hemoprotein in the yeast Saccharomyces cerevisiae. AB - The Saccharomyces cerevisiae gene YNL234w encodes a 426-amino acid-long protein that shares significant similarities with the globin family. Compared with known globins from unicellular organisms, the Ynl234wp polypeptide is characterized by an unusual structure. In this protein, a central putative heme-binding domain of about 140 amino acids is flanked by two sequences of about 160 and 120 amino acids, respectively, which share no similarity with known polypeptides. Northern analysis indicates that YNL234w transcription is very low in cells grown under normal aerobic conditions but is induced by oxygen-limited growth conditions and by other stress conditions such as glucose repression, heat shock, osmotic stress, and nitrogen starvation. However, the deletion of the gene had no detectable effect on yeast growth. The Ynl234wp polypeptide has been expressed in Escherichia coli, and the hemoprotein nature of the recombinant protein was demonstrated by heme staining after SDS/polyacrylamide gel electrophoresis and spectroscopic analysis. Our data indicate that purified recombinant Ynl234wp possesses a noncovalently bound heme molecule that is predominantly found in a low spin form. PMID- 9988750 TI - Oxidative damage of cardiomyocytes is limited by extracellular regulated kinases 1/2-mediated induction of cyclooxygenase-2. AB - Oxidative stress causes cardiac damage following ischemia/reperfusion and in response to anthracyclines. Extracellular signal-regulated kinases (ERK) 1/2 are activated by oxidative stress in cardiac myocytes and protect cardiac myocytes from apoptosis. Prostaglandins (PG) also protect cells from injury in a number of tissues, including the cardiomyocyte. Cyclooxygenase (COX) the rate-limiting enzyme in PG biosynthesis has two isoforms, the constitutive COX-1 and an inducible COX-2. Here, we examined the effects of two oxidative stresses, hydrogen peroxide (H2O2) and the anthracycline doxorubicin on the activity of ERK1/2 and the expression of COX isoforms and PG formation in neonatal rat primary cardiomyocytes. These cells expressed COX-1 at rest and both COX isoforms on treatment with phorbol 12-myristate 13-acetate. Exposure to 50 microM H2O2 for 10 min or doxorubicin at 10 and 100 micrograms/ml caused expression of COX-2 that was prevented by free radical scavengers. COX-2 induction was associated with activation of ERK1/2 and the specific ERK-inhibitor PD098059 abolished COX-2 expression. Treatment of cells with decoy oligonucleotides corresponding to COX-2 promoter elements implicated the AP-1 and NF-kappaB-2 but not the NF-kappaB-1 in the transcription of COX-2. Induction of COX-2 mRNA and protein was accompanied by increased prostacyclin formation, which was abolished by the selective COX-2 inhibitor, NS-398, and PD098059. H2O2 and doxorubicin enhanced the release of lactate dehydrogenase and free radical scavengers prevented this. NS-398 enhanced the release of lactate dehydrogenase in response to H2O2 and doxorubicin, whereas the injury was prevented by iloprost, a stable prostacyclin analogue. In cardiomyocytes cell injury by H2O2 and doxorubicin is limited by an increase in prostacyclin formation that reflects induction of COX-2 mediated by ERK1/2 activation. PMID- 9988751 TI - Hypoxia post-translationally activates iron-regulatory protein 2. AB - Iron-regulatory proteins 1 and 2 (IRP1 and IRP2) are RNA-binding proteins that post-transcriptionally regulate the expression of mRNAs that code for proteins involved in the maintenance of iron and energy homeostasis. Here we show that hypoxia differentially regulates the RNA binding activities of IRP1 and IRP2 in human 293 and in mouse Hepa-1 cells. In contrast to IRP1, where hypoxic exposure decreases IRP1 RNA binding activity, hypoxia increases IRP2 RNA binding activity. The hypoxic increase in IRP2 RNA binding activity results from increased IRP2 protein levels. Cobalt, which mimics hypoxia by activation of hypoxia-inducible factor 1 (HIF-1), also increases IRP2 protein levels; however, cobalt-induced IRP2 lacks RNA binding activity. Addition of a reductant to cobalt-treated extracts restored IRP2 RNA binding activity. Hypoxic activation of IRP2 is not because of an increase in transcriptional activation by HIF-1, because IRP2 accumulates in Hepa-1 cells lacking a functional HIF-1beta subunit, nor is it because of an increase in IRP2 mRNA stability. Rather, our data indicate that hypoxia increases IRP2 levels by a post-translational mechanism involving protein stability. Differential regulation of IRP1 and IRP2 during hypoxia may regulate specific IRP target mRNAs whose expression is required for hypoxic adaptation. Furthermore, these data imply mechanistic parallels between the hypoxia-induced post-transcriptional regulation of IRP2 and HIF-1alpha. PMID- 9988752 TI - Distinct caspase cascades are initiated in receptor-mediated and chemical-induced apoptosis. AB - Release of cytochrome c is important in many forms of apoptosis. Recent studies of CD95 (Fas/APO-1)-induced apoptosis have implicated caspase-8 cleavage of Bid, a BH3 domain-containing proapoptotic member of the Bcl-2 family, in this release. We now demonstrate that both receptor-induced (CD95 and tumor necrosis factor) and chemical-induced apoptosis result in a similar time-dependent activation of caspases-3, -7, -8, and -9 in Jurkat T cells and human leukemic U937 cells. In receptor-mediated apoptosis, the caspase inhibitor, benzyloxycarbonyl-Val-Ala-Asp fluoromethyl ketone (Z-VAD. FMK), inhibits apoptosis prior to commitment to cell death by inhibiting the upstream activator caspase-8, cleavage of Bid, release of mitochondrial cytochrome c, processing of effector caspases, loss of mitochondrial membrane potential, and externalization of phosphatidylserine. However, Z-VAD.FMK inhibits chemical-induced apoptosis at a stage after commitment to cell death by inhibiting the initiator caspase-9 and the resultant postmitochondrial activation of effector caspases. Cleavage of Bid but not release of cytochrome c is blocked by Z-VAD.FMK demonstrating that in chemical induced apoptosis cytochrome c release is caspase-independent and is not mediated by activation of Bid. We propose that caspases form an integral part of the cell death-inducing mechanism in receptor-mediated apoptosis, whereas in chemical induced apoptosis they act solely as executioners of apoptosis. PMID- 9988753 TI - Protection of neuronal cells from apoptosis by Hsp27 delivered with a herpes simplex virus-based vector. AB - Overexpression of the gene encoding the 70-kDa heat shock protein (hsp70) has previously been shown to protect neuronal cells against subsequent thermal or ischemic stress. It has no protective effect, however, against stimuli that induce apoptosis, although a mild heat shock (sufficient to induce hsp synthesis) does have a protective effect against apoptosis. We have prepared disabled herpes simplex virus-based vectors that are able to produce high level expression of individual hsps in infected neuronal cells without damaging effects. We have used these vectors to show that hsp27 and hsp56 (which have never previously been overexpressed in neuronal cells) as well as hsp70 can protect dorsal root ganglion neurons from thermal or ischemic stress. In contrast, only hsp27 can protect dorsal root ganglion neurons from apoptosis induced by nerve growth factor withdrawal, and hsp27 also protects the ND7 neuronal cell line from retinoic acid-induced apoptosis. However, hsp70 showed no protective effect against apoptosis in contrast to its anti-apoptotic effect in non-neuronal cell types. These results thus identify hsp27 as a novel neuroprotective factor and show that it can mediate this effect when delivered via a high efficiency viral vector. PMID- 9988754 TI - Editing of glutamate receptor subunit B pre-mRNA by splice-site variants of interferon-inducible double-stranded RNA-specific adenosine deaminase ADAR1. AB - The interferon-inducible RNA-specific adenosine deaminase (ADAR1) is an RNA editing enzyme that catalyzes the deamination of adenosine in double-stranded RNA structures. Three alternative splice-site variants of ADAR1 (ADAR1-a, -b, and -c) occur that possess functionally distinct double-stranded RNA-binding motifs as measured with synthetic double-stranded RNA substrates. The pre-mRNA transcript encoding the B subunit of glutamate receptor (GluR-B) has two functionally important editing sites (Q/R and R/G sites) that undergo selective A-to-I conversions. We have examined the ability of the three ADAR1 splice-site variants to catalyze the editing of GluR-B pre-mRNA at the Q/R and R/G sites as well as an intron hotspot (+60) of unknown function. Measurement of GluR-B pre-mRNA editing in vitro revealed different site-specific deamination catalyzed by the three ADAR1 variants. The ADAR1-a, -b, and -c splice variants all efficiently edited the R/G site and the intron +60 hotspot but exhibited little editing activity at the Q/R site. ADAR1-b and -c showed higher editing activity than ADAR1-a for the R/G site, whereas the intron +60 site was edited with comparable efficiency by all three ADAR1 splice variants. Mutational analysis revealed that the functional importance of each of the three RNA-binding motifs of ADAR1 varied with the specific target editing site in GluR-B RNA. Quantitative reverse transcription polymerase chain reaction analyses of GluR-B RNA from dissected regions of rat brain showed significant expression and editing at the R/G site in all brain regions examined except the choroid plexus. The relative levels of the alternatively spliced flip and flop isoforms of GluR-B RNA varied among the choroid plexus, cortex, hippocampus, olfactory bulb, and striatum, but in all regions of rat brain the editing of the flip isoform was greater than that of the flop isoform. PMID- 9988755 TI - Presence of a structurally novel type ribulose-bisphosphate carboxylase/oxygenase in the hyperthermophilic archaeon, Pyrococcus kodakaraensis KOD1. AB - We have characterized the gene encoding ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco) of the hyperthermophilic archaeon, Pyrococcus kodakaraensis KOD1. The gene encoded a protein consisting of 444 amino acid residues, corresponding in size to the large subunit of previously reported Rubiscos. Rubisco of P. kodakaraensis KOD1 (Pk-Rubisco) showed only 51.4% similarity with the large subunit of type I Rubisco from spinach and 47.3% with that of type II Rubisco from Rhodospirillum rubrum, suggesting that the enzyme was not a member of either type. Active site residues identified from type I and type II Rubiscos were conserved. We expressed the gene in Escherichia coli, and we obtained a soluble protein with the expected molecular mass and N-terminal amino acid sequence. Purification of the recombinant protein revealed that Pk Rubisco was an L8 type homo-octamer. Pk-Rubisco showed highest specific activity of 19.8 x 10(3) nmol of CO2 fixed per min/mg, and a tau value of 310 at 90 degreesC, both higher than any previously characterized Rubisco. The optimum pH was 8.3, and the enzyme possessed extreme thermostability, with a half-life of 15 h at 80 degreesC. Northern blot analysis demonstrated that the gene was transcribed in P. kodakaraensis KOD1. Furthermore, Western blot analysis with cell-free extract of P. kodakaraensis KOD1 clearly indicated the presence of Pk Rubisco in the native host cells. PMID- 9988756 TI - Targeted reduction of nucleoside triphosphate hydrolase by antisense RNA inhibits Toxoplasma gondii proliferation. AB - Nucleoside triphosphate hydrolase (NTPase) is a very abundant protein secreted by the obligate intracellular parasite Toxoplasma gondii shortly after invasion of the host cell. When activated by dithiols, NTPase is one of the most potent apyrases known to date, but its physiological function remains unknown. The genes encoding NTPase have been cloned (Bermudes, D., Peck, K. R., Afifi-Afifi, M., Beckers, C. J. M., and Joiner, K. A. (1994) J. Biol. Chem. 269, 29252-29260). We have recently shown that the enzyme is tightly controlled within the vacuolar space and may influence parasite exit from the host cell (Silverman, J. A., Qi, H., Riehl, A., Beckers, C., Nakaar, V., and Joiner, K. A (1998) J. Biol. Chem. 273, 12352-12359). In the present study, we have generated an antisense NTP RNA construct in which the 3'-untranslated region is replaced by a hammerhead ribozyme. The constitutive synthesis of the chimeric antisense RNA-ribozyme construct in parasites that were stably transfected with this construct resulted in a dramatic reduction in the steady-state levels of NTPase. This inhibition was accompanied by a decrease in the capacity of the parasites to replicate. The reduction in parasite proliferation was due to a specific effect of antisense NTP RNA, since a drastic inhibition of hypoxanthine-xanthine-guanine phosphoribosyl transferase (HXGPRT) expression by a chimeric antisense HXGPRT RNA-ribozyme construct did not alter NTPase expression nor compromise parasite replication. These data implicate NTPase in an essential parasite function and suggest that NTPase may have more than one function in vivo. These results also establish that it is possible to study gene function in apicomplexan parasites using antisense RNA coupled to ribozymes. PMID- 9988757 TI - Molecular mechanism of the regulation of glutathione synthesis by tumor necrosis factor-alpha and dexamethasone in human alveolar epithelial cells. AB - Glutathione (GSH) is an important physiological antioxidant in lung epithelial cells and lung lining fluid. We studied the regulation of GSH synthesis in response to the pro-inflammatory cytokine tumor necrosis factor-alpha (TNF-alpha) and the anti-inflammatory agent dexamethasone in human alveolar epithelial cells (A549). TNF-alpha (10 ng/ml) exposure increased GSH levels, concomitant with a significant increase in gamma-glutamylcysteine synthetase (gamma-GCS) activity and the expression of gamma-GCS heavy subunit (gamma-GCS-HS) mRNA at 24 h. Treatment with TNF-alpha also increased chloramphenicol acetyltransferase (CAT) activity of a gamma-GCS-HS 5'-flanking region reporter construct, transfected into alveolar epithelial cells. Mutation of the putative proximal AP-1-binding site (-269 to -263 base pairs), abolished TNF-alpha-mediated activation of the promoter. Gel shift and supershift analysis showed that TNF-alpha increased AP-1 DNA binding which was predominantly formed by dimers of c-Jun. Dexamethasone (3 microM) produced a significant decrease in the levels of GSH, decreased gamma-GCS activity and gamma-GCS-HS mRNA expression at 24 h. The increase in GSH levels, gamma-GCS-HS mRNA, gamma-GCS-HS promoter activity, and AP-1 DNA binding produced by TNF-alpha were abrogated by co-treating the cells with dexamethasone. Thus these data demonstrate that TNF-alpha and dexamethasone modulate GSH levels and gamma-GCS-HS mRNA expression by their effects on AP-1 (c-Jun homodimer). These data have implications for the oxidant/antioxidant balance in inflammatory lung diseases. PMID- 9988758 TI - Herpes simplex virus type 1 infection stimulates p38/c-Jun N-terminal mitogen activated protein kinase pathways and activates transcription factor AP-1. AB - Cells respond to environmental stress and proinflammatory cytokines by stimulating the Jun N-terminal kinase/stress-activated protein kinase (JNK/SAPK) and the p38 mitogen-activated protein kinase cascades. Infection of eukaryotic cells with herpes simplex virus type 1 (HSV-1) resulted in stimulation of both JNK/SAPK and p38 mitogen-activated protein kinase after 3 h of infection, and activation reached a maximum of 4-fold by 9 h post-infection. By using a series of mutant viruses, we showed that the virion transactivator protein VP16 stimulates p38/JNK, whereas no immediate-early, early, or late viral expressed gene is involved. We identified the stress-activated protein kinase kinase 1 as an upstream activator of p38/JNK, and we demonstrated that activation of AP-1 binding proceeded p38/JNK stimulation. During infection, the activated AP-1 consisted mainly of JunB and JunD with a simultaneous decrease in the cellular levels of Jun protein. We suggest that activation of the stress pathways by HSV-1 infection either represents a cascade triggered by the virus to facilitate the lytic cycle or a defense mechanism of the host cell against virus invasion. PMID- 9988759 TI - Functional organization of two large subunits of the fission yeast Schizosaccharomyces pombe RNA polymerase II. Location of the catalytic sites. AB - The catalytically competent transcription complex of RNA polymerase II from the fission yeast Schizosaccharomyces pombe was affinity labeled with photoreactive nucleotide analogues incorporated at 3' termini of nascent RNA chains. To locate the catalytic site for RNA polymerization, the labeled subunits were separated by SDS-polyacrylamide gel electrophoresis and subjected to partial proteolysis. After microsequencing of proteolytic fragments, a complex multidomain organization was indicated for both of the two large subunits, Rpb1 and Rpb2, with the most available sites of proteolysis in junctions between the conserved sequences among RNA polymerase from both prokaryotes and eukaryotes. The cross linking studies indicate the following: (i) the 3' termini of growing RNA chains are most extensively cross-linked to the second largest subunit Rpb2 between amino acids 825 and 994; (ii) the regions 298-535 of Rpb2 and 614-917 of Rpb1 are cross-linked to less extents, suggesting that these regions are situated in the vicinity of the catalytic site. All these regions include the conserved sequences of RNA polymerases, and the catalytic site of Rpb2 belongs to an NH2-terminal part of its conserved sequence H. PMID- 9988760 TI - Non-lamellar structure and negative charges of lipopolysaccharides required for efficient folding of outer membrane protein PhoE of Escherichia coli. AB - Lipopolysaccharides (LPS) are amphiphilic molecules in the outer leaflet of the bacterial outer membrane. Recently, an early role for LPS in the folding of outer membrane porin PhoE was demonstrated in vitro. In order to elucidate the molecular mechanism of LPS-protein interactions, folding of PhoE protein was studied with a large set of well characterized LPS chemotypes. We demonstrate that negative charges in the inner core region contribute to the high efficiency of folding of PhoE protein. In addition, the supramolecular structure of the LPS aggregate seems to be important. LPS with a lipid A part that prefers a lamellar or a direct micellar structure and a high state of order of its acyl chains is much less efficient to support folding as compared with LPS with lipid A that prefers a non-lamellar structure and a low acyl chain order. These in vitro data indicate that extensive interactions between the core and lipid A region of LPS with the protein are required to support protein folding. The LPS-PhoE binding might be promoted by the presence of hydroxy fatty acids in the lipid A moiety of LPS. PMID- 9988761 TI - Identification of residues within the 727-767 segment of human complement component C3 important for its interaction with factor H and with complement receptor 1 (CR1, CD35). AB - Mapping approaches employing blocking antibodies and synthetic peptides have implicated the 727-767 segment at the NH2 terminus of C3b alpha'-chain as contributing to the interactions with factor B, factor H, and CR1. Our previous mutagenesis study on the NH2-terminal acidic cluster of this segment identified residues Glu-736 and Glu-737 as contributing to the binding of C3b to factor B and CR1 but not factor H. We have now extended the charged residue mutagenic scan to cover the remainder of the segment (738-767) and have assessed the ability of the C3b-like C3(H2O) form of the mutant molecules to interact with factor H, CR1, and membrane cofactor protein (MCP) using a cofactor-dependent factor I cleavage assay as a surrogate binding assay. We have found that the negatively charged side chains of Glu-744 and Glu-747 are important for the interaction between C3(H2O) and factor H, a result in general agreement with an earlier synthetic peptide study (Fishelson, Z. (1991) Mol. Immunol. 28, 545-552) which implicated residues within the 744-754 segment in H binding. The interactions of the mutants with soluble CR1 (sCR1) revealed two classes of residues. The first are residues required for sCR1 to be an I cofactor for the first two cleavages of alpha-chain. These are all acidic residues and include the Glu-736/Glu-737 pair, Glu-747, and the Glu-754/Asp-755 pairing. The second class affects only the ability of sCR1 to be a cofactor for the third factor I cleavage and include Glu-744 and the Lys 757/Glu-758 pairing. The dominance of acidic residues in the loss-of-function mutants is striking and suggests that H and CR1 contribute basic residues to the interface. Additionally, although there is partial overlap, the contacts required for CR1 binding appear to extend over a wider portion of the 727-767 segment than is the case for factor H. Finally, none of the mutations had any effect on the interaction between soluble MCP and C3(H2O), indicating that despite its functional homology to H and CR1, MCP differs in its mode of binding to C3b/C3(H2O). PMID- 9988762 TI - The cloning and characterization of a new stress response protein. A mammalian member of a family of theta class glutathione s-transferase-like proteins. AB - Using differential display, a cDNA fragment was identified as being overexpressed in a mouse lymphoma cell line that had gained resistance to cell death after exposure to a variety of agents used in cancer therapy. The full-length cDNA of 1.1 kb that was cloned contained an open reading frame coding for a previously unidentified 28-kDa mammalian protein, p28. p28 showed significant homologies to a large family of stress response proteins that contain a glutathione S transferase (GST) domain. In correspondence with the sequence homology, p28 was found to bind glutathione; however, GST or glutathione peroxidase activity could not be demonstrated. Northern analysis of the mRNA of this protein showed abundant expression in mouse heart and liver tissues, whereas anti-p28 antibody binding identified p28 expression in mouse 3T3 cells and early passage mouse embryo fibroblasts. Subcellular protein fractionation revealed p28 localization in the cytoplasm, but with thermal stress p28 relocated to the nuclear fraction of cellular proteins. Based on sequence homology and protein activity we conclude that p28 acts as a small stress response protein, likely involved in cellular redox homeostasis, and belongs to a family of GST-like proteins related to class theta GSTs. PMID- 9988763 TI - A functional DNA binding domain is required for growth hormone-induced nuclear accumulation of Stat5B. AB - The mechanisms regulating the cellular distribution of STAT family transcription factors remain poorly understood. To identify regions of Stat5B required for ligand-induced nuclear accumulation, we constructed a cDNA encoding green fluorescent protein (GFP) fused to the N terminus of Stat5B and performed site directed mutagenesis. When co-expressed with growth hormone (GH) receptor in COS 7 cells, GFP-Stat5B is tyrosyl-phosphorylated, forms dimers, and binds DNA in response to GH in a manner indistinguishable from untagged Stat5B. In multiple cell types, laser scanning confocal imaging of GFP-Stat5B co-expressed with GH receptor shows that GFP-Stat5B undergoes a rapid, dramatic accumulation in the nucleus upon GH stimulation. We introduced alanine substitutions in several regions of Stat5B and assayed for GH-dependent nuclear localization. Only the mutation that prevented binding to DNA (466VVVI469) abrogated GH-stimulated nuclear localization. This mutant fusion protein is tyrosyl-phosphorylated and dimerizes in response to GH. These results suggest that either high affinity binding to DNA contributes to nuclear accumulation of Stat5B or that this region is crucial for two functions, namely accumulation of Stat5B in the nucleus and DNA binding. Thus, we have identified a mutant Stat5 defective in nuclear localization despite its ability to be tyrosyl-phosphorylated and to dimerize. PMID- 9988764 TI - The lck SH3 domain is required for activation of the mitogen-activated protein kinase pathway but not the initiation of T-cell antigen receptor signaling. AB - Initiation of T-cell antigen receptor (TCR) signaling is dependent upon the activity of protein tyrosine kinases. The Src family kinase Lck is required for the initial events in TCR signaling, such as the phosphorylation of the TCR complex and the activation of ZAP-70, but little is known of its role in downstream signaling. Expression of a mutated form of Lck lacking SH3 domain function (LckW97A) in the Lck-deficient T-cell line JCaM1 revealed a requirement for Lck beyond the initiation of TCR signaling. In cells expressing LckW97A, stimulation of the TCR failed to activate the mitogen-activated protein kinase (MAPK) pathway, despite normal TCR zeta chain phosphorylation, ZAP-70 recruitment, and ZAP-70 activation. Activation of extracellular signal-regulated kinase (ERK) and MAPK kinase (MEK), as well as the induction of CD69 expression, was greatly impaired in JCaM1/LckW97A cells. In contrast, the phosphorylation of phospholipase Cgamma1 (PLCgamma1) and corresponding elevations in intracellular calcium concentration ([Ca2+]i) were intact. Thus, cells expressing LckW97A exhibit a selective defect in the activation of the MAPK pathway. These results demonstrate that Lck has a role in the activation of signaling pathways beyond the initiation of TCR signaling and suggest that the MAPK pathway may be selectively controlled by regulating the function of Lck. PMID- 9988765 TI - Activation of nuclear factor of activated T cells-(NFAT) and activating protein 1 (AP-1) by oncogenic 70Z Cbl requires an intact phosphotyrosine binding domain but not Crk(L) or p85 phosphatidylinositol 3-kinase association. AB - The Cbl proto-oncogene product is a complex adapter protein that functions as a negative regulator of protein tyrosine kinases. It is rapidly tyrosine phosphorylated and associates with Crk(L) and p85 phosphatidylinositol 3-kinase (PI3K) upon engagement of numerous receptors linked to tyrosine kinases. Elucidation of the mechanism(s) underlying Cbl deregulation is therefore of considerable interest. The 70Z Cbl oncoprotein shows increased baseline tyrosine phosphorylation in fibroblasts and enhances nuclear factor of activated T cells (NFAT) activity in Jurkat T cells. Its transforming ability has been proposed to relate to its increased phosphotyrosine content. We demonstrate that 70Z Cbl shows increased basal and activation-induced tyrosine phosphorylation and association with Crk(L) and p85 PI3K in Jurkat T cells. 70Z Cbl, however, retains the ability to enhance NFAT and activating protein 1 (AP1) activity in the absence of Crk(L)/p85 PI3K association. In contrast, the G306E mutation, which inactivates the phosphotyrosine binding domain of Cbl, blocks NFAT/AP1 activation by 70Z Cbl. We conclude that 70Z Cbl-induced NFAT/AP1 activation requires the phosphotyrosine binding domain but not Crk(L)/p85 PI3K association. We hypothesize that 70Z Cbl acts as a dominant negative by blocking the negative regulatory function of the Cbl phosphotyrosine binding domain on protein-tyrosine kinases. PMID- 9988766 TI - Critical duration of intracellular Ca2+ response required for continuous translocation and activation of cytosolic phospholipase A2. AB - When cells are exposed to certain external stimuli, arachidonic acid (AA) is released from the membrane and serves as a precursor of various types of eicosanoids. A Ca2+-regulated cytosolic phospholipase A2 (cPLA2) plays a dominant role in the release of AA. To closely examine the relation between Ca2+ response and AA release by stimulation of G protein-coupled receptors, we established several lines of Chinese hamster ovary cells expressing platelet-activating factor receptor or leukotriene B4 receptor. Measurement of intracellular Ca2+ concentration ([Ca2+]i) demonstrated that cell lines capable of releasing AA elicited a sustained [Ca2+]i increase when stimulated by agonists. The prolonged [Ca2+]i elevation is the result of Ca2+ entry, because this elevation was blocked by EGTA treatment or in the presence of Ca2+ channel blockers (SKF 96365 and methoxyverapamil). cPLA2 fused with a green fluorescent protein (cPLA2-GFP) translocated from the cytosol to the perinuclear region in response to increases in [Ca2+]i. When EGTA was added shortly after [Ca2+]i increase, the cPLA2-GFP returned to the cytosol, without liberating AA. After a prolonged [Ca2+]i increase, even by EGTA treatment, the enzyme was not readily redistributed to the cytosol. Thus, we propose that a critical time length of [Ca2+]i elevation is required for continuous membrane localization and full activation of cPLA2. PMID- 9988767 TI - Multiple isoforms of heparan sulfate D-glucosaminyl 3-O-sulfotransferase. Isolation, characterization, and expression of human cdnas and identification of distinct genomic loci. AB - 3-O-Sulfated glucosaminyl residues are rare constituents of heparan sulfate and are essential for the activity of anticoagulant heparan sulfate. Cellular production of the critical active structure is controlled by the rate-limiting enzyme, heparan sulfate D-glucosaminyl 3-O-sulfotransferase-1 (3-OST-1) (EC 2.8.2.23). We have probed the expressed sequence tag data base with the carboxyl terminal sulfotransferase domain of 3-OST-1 to reveal three novel, incomplete human cDNAs. These were utilized in library screens to isolate full-length cDNAs. Clones corresponding to predominant transcripts were obtained for the 367-, 406-, and 390-amino acid enzymes 3-OST-2, 3-OST-3A, and 3-OST-3B, respectively. These type II integral membrane proteins are comprised of a divergent amino-terminal region and a very homologous carboxyl-terminal sulfotransferase domain of approximately 260 residues. Also recovered were partial length clones for 3-OST 4. Expression of the full-length enzymes confirms the 3-O-sulfation of specific glucosaminyl residues within heparan sulfate (Liu, J., Shworak, N. W., Sinay, P., Schwartz, J. J. Zhang, L., Fritze, L. M. S., and Rosenberg, R. D. (1999) J. Biol. Chem. 274, 5185-5192). Southern analyses suggest the human 3OST1, 3OST2, and 3OST4 genes, and the corresponding mouse isologs, are single copy. However, 3OST3A and 3OST3B genes are each duplicated in humans and show at least one copy each in mice. Intriguingly, the entire sulfotransferase domain sequence of the 3 OST-3B cDNA (774 base pairs) was 99.2% identical to the same region of 3-OST-3A. Together, these data argue that the structure of this functionally important region is actively maintained by gene conversion between 3OST3A and 3OST3B loci. Interspecific mouse back-cross analysis identified the loci for mouse 3Ost genes and syntenic assignments of corresponding human isologs were confirmed by the identification of mapped sequence-tagged site markers. Northern blot analyses indicate brain exclusive and brain predominant expression of 3-OST-4 and 3-OST-2 transcripts, respectively; whereas, 3-OST-3A and 3-OST-3B isoforms show widespread expression of multiple transcripts. The reiteration and conservation of the 3-OST sulfotransferase domain suggest that this structure is a self contained functional unit. Moreover, the extensive number of 3OST genes with diverse expression patterns of multiple transcripts suggests that the novel 3-OST enzymes, like 3-OST-1, regulate important biologic properties of heparan sulfate proteoglycans. PMID- 9988768 TI - Expression of heparan sulfate D-glucosaminyl 3-O-sulfotransferase isoforms reveals novel substrate specificities. AB - The 3-O-sulfation of glucosamine residues is an important modification during the biosynthesis of heparan sulfate (HS). Our previous studies have led us to purify and molecularly clone the heparan sulfate D-glucosaminyl 3-O-sulfotransferase (3 OST-1), which is the key enzyme converting nonanticoagulant heparan sulfate (HSinact) to anticoagulant heparan sulfate (HSact). In this study, we expressed and characterized the full-length cDNAs of 3-OST-1 homologous genes, designated as 3-OST-2, 3-OST-3A, and 3-OST-3B as described in the accompanying paper (Shworak, N. W., Liu, J., Petros, L. M., Zhang, L., Kobayashi, M., Copeland, N. G., Jenkins, N. A., and Rosenberg, R. D. (1999) J. Biol. Chem. 274, 5170-5184). All these cDNAs were successfully expressed in COS-7 cells, and heparan sulfate sulfotransferase activities were found in the cell extracts. We demonstrated that 3-OST-2, 3-OST-3A, and 3-OST-3B are heparan sulfate D-glucosaminyl 3-O sulfotransferases because the enzymes transfer sulfate from adenosine 3' phosphophate 5'-phospho-[35S]sulfate ([35S]PAPS) to the 3-OH position of glucosamine. 3-OST-3A and 3-OST-3B sulfate an identical disaccharide. HSact conversion activity in the cell extract transfected by 3-OST-1 was shown to be 300-fold greater than that in the cell extracts transfected by 3-OST-2 and 3-OST 3A, suggesting that 3-OST-2 and 3-OST-3A do not make HSact. The results of the disaccharide analysis of the nitrous acid-degraded [35S]HS suggested that 3-OST-2 transfers sulfate to GlcA2S-GlcNS and IdoA2S-GlcNS; 3-OST-3A transfers sulfate to IdoA2S-GlcNS. Our results demonstrate that the 3-O-sulfation of glucosamine is generated by different isoforms depending on the saccharide structures around the modified glucosamine residue. This discovery has provided evidence for a new cellular mechanism for generating a defined saccharide sequence in structurally complex HS polysaccharide. PMID- 9988769 TI - p38 mitogen-activated protein kinase pathway promotes skeletal muscle differentiation. Participation of the Mef2c transcription factor. AB - Differentiation of muscle cells is regulated by extracellular growth factors that transmit largely unknown signals into the cells. Some of these growth factors induce mitogen-activated protein kinase (MAPK) cascades within muscle cells. In this work we show that the kinase activity of p38 MAPK is induced early during terminal differentiation of L8 cells. Addition of a specific p38 inhibitor SB 203580 to myoblasts blocked their fusion to multinucleated myotubes and prevented the expression of MyoD and MEF2 family members and myosin light chain 2. The expression of MKK6, a direct activator of p38, or of p38 itself enhanced the activity of MyoD in converting 10T1/2 fibroblasts to muscle, whereas treatment with SB 203580 inhibited MyoD. Several lines of evidence suggesting that the involvement of p38 in MyoD activity is mediated via its co-activator MEF2C, a known substrate of p38, are presented. In these experiments we show that MEF2C protein and MEF2-binding sites are necessary for the p38 MAPK pathway to regulate the transcription of muscle creatine kinase reporter gene. Our results indicate that the p38 MAPK pathway promotes skeletal muscle differentiation at least in part via activation of MEF2C. PMID- 9988770 TI - The molecular weights, mass distribution, chain composition, and structure of soluble fibrin degradation products released from a fibrin clot perfused with plasmin. AB - We used a perfused clot system to study the degradation of cross-linked fibrin. Multiangle laser light scattering showed that plasmin-mediated cleavage caused the release of noncovalently associated fibrin degradation products (FDPs) with a weight-averaged molar mass (Mw) of approximately 6 x 10(6) g/mol. The Mw of FDPs is dependent on ionic strength, and the Mw observed at 0.15 M NaCl resulted from the self-association of FDPs having Mw of approximately 3.8 x 10(6) g/mol. Complete solubilization required the cleavage of approximately 25% of fragment D/fragment E connections, with 48% alpha-, 62% beta-, and 42% gamma-chains cleaved. These results showed that D-E cleavage cannot be explained by a random mechanism, implying cooperativity. Gel filtration and multiangle laser light scattering showed that FDPs range from 2.5 x 10(5) to 1 x 10(7) g/mol. In addition to fragment E, FDPs are composed of fragments ranging from 2 x 10(5) Da (D-dimer, or DD) to at least 2.3 x 10(6) Da (DX8D). FDP mass distribution is consistent with a model whereby FDPs bind to fibrin with affinities proportional to fragment mass. Root mean square radius analysis showed that small FDPs approximate rigid rods, but this relationship breaks down as FDPs size increases, suggesting that large FDPs possess significant flexibility. PMID- 9988771 TI - Regions of endonuclease EcoRII involved in DNA target recognition identified by membrane-bound peptide repertoires. AB - Target sequence-specific DNA binding regions of the restriction endonuclease EcoRII were identified by screening a membrane-bound EcoRII-derived peptide scan with an EcoRII recognition site (CCWGG) oligonucleotide duplex. Dodecapeptides overlapping by nine amino acids and representing the complete protein were prepared by spot synthesis. Two separate DNA binding regions, amino acids 88-102 and amino acids 256-273, which share the consensus motif KXRXXK, emerged. Screening 570 single substitution analogues obtained by exchanging every residue of both binding sites for all other amino acids demonstrated that replacing basic residues in the consensus motifs significantly reduced DNA binding. EcoRII mutant enzymes generated by substituting alanine or glutamic acid for the consensus lysine residues in DNA binding site I expressed attenuated DNA binding, whereas corresponding substitutions in DNA binding site II caused impaired cleavage, but enzyme secondary structure was unaffected. Furthermore, Glu96, which is part of a potential catalytic motif and also locates to DNA binding site I, was demonstrated to be critical for DNA cleavage and binding. Homology studies of DNA binding site II revealed strong local homology to SsoII (recognition sequence, CCNGG) and patterns of sequence conservation, suggesting the existence of functionally related DNA binding sites in diverse restriction endonucleases with recognition sequences containing terminal C:G or G:C pairs. PMID- 9988772 TI - Fragmentation of the large subunit of ribulose-1,5-bisphosphate carboxylase by reactive oxygen species occurs near Gly-329. AB - The large subunit (LSU) of ribulose-1,5-bisphosphate carboxylase/oxygenase (rubisco) in the illuminated lysates of wheat (Triticum aestivum L.) chloroplasts is broken down by reactive oxygen radicals into 37- and 16-kDa polypeptides. Analysis of the terminal amino acid residues of both fragments revealed that the C terminus of the 37-kDa fragment was Ser-328 and the N terminus of the 16-kDa fragment was Thr-330. Gly-329, which links the two fragments, was missing, suggesting that the fragmentation of the LSU in the lysates driven by oxygen-free radicals occurs at Gly-329. Purified rubisco, exposed to a hydroxyl radical generating system, was also cleaved at the same site of the LSU. The cleavage site was positioned at the N-terminal end of the flexible loop (loop 6) within the beta/alpha-barrel domain, constituting the catalytic site of rubisco. The binding of a reaction intermediate analogue, 2-carboxyarabinitol 1,5 bisphosphate, to the active form of rubisco completely protected the enzyme from the fragmentation. The fragmentation was differentially affected by CO2, Mg2+, ribulose 1, 5-bisphosphate, or 2-carboxyarabinitol 1,5-bisphosphate. All these results indicate that the conformation of the catalytic site of the enzyme is involved as an important factor determining the breakdown of rubisco by reactive oxygen species. Reactive oxygen species generated at its catalytic site by a Fenton-type reaction may trigger the site-specific degradation of the LSU in the lysates of chloroplasts in the light. PMID- 9988773 TI - In vitro evolution of preferred topoisomerase II DNA cleavage sites. AB - Topoisomerase II is an essential enzyme that is the target for several clinically important anticancer drugs. Although this enzyme must create transient double stranded breaks in the genetic material in order to carry out its indispensable DNA strand passage reaction, the factors that underlie its nucleotide cleavage specificity remain an enigma. Therefore, to address the critical issue of enzyme specificity, a modified systematic evolution of ligands by exponential enrichment (SELEX) protocol was employed to select/evolve DNA sequences that were preferentially cleaved by Drosophila melanogaster topoisomerase II. Levels of DNA scission rose substantially (from 3 to 20%) over 20 rounds of SELEX. In vitro selection/evolution converged on an alternating purine/pyrmidine sequence that was highly AT-rich (TATATATACATATATATA). The preference for this sequence was more pronounced for Drosophila topoisomerase II over other species and was increased in the presence of DNA cleavage-enhancing anticancer drugs. Enhanced cleavage appeared to be based on higher rates of DNA scission rather than increased binding affinity or decreased religation rates. The preferred sequence for topoisomerase II-mediated DNA cleavage is dramatically overrepresented ( approximately 10,000-fold) in the euchromatic genome of D. melanogaster, implying that it may be a site for the physiological action of this enzyme. PMID- 9988774 TI - Heparan sulfate mediates bFGF transport through basement membrane by diffusion with rapid reversible binding. AB - Basic fibroblast growth factor (bFGF) is a pluripotent cytokine with a wide range of target cells. Heparan sulfate binds bFGF, and this interaction has been demonstrated to protect bFGF against physical denaturation and protease degradation. The high concentrations of heparan sulfate in basement membranes have implicated these matrices as storage sites for bFGF in vivo. However, the mechanisms by which basement membranes modulate bFGF storage and release is unknown. To gain insight into these mechanisms, we have developed experimental and mathematical models of extracellular growth factor transport through basement membrane. Intact Descemet's membranes isolated from bovine corneas were mounted within customized diffusion cells and growth factor transport was measured under a variety of conditions that decoupled the diffusion process from the heparan sulfate binding phenomenon. Transport experiments were conducted with bFGF and interleukin 1beta. In addition, bFGF-heparan sulfate binding was disrupted in diffusion studies with high ionic strength buffer and buffers containing protamine sulfate. Transport of bFGF was enhanced dramatically when heparan sulfate binding was inhibited. This process was modeled as a problem of diffusion with fast reversible binding. Experimental parameters were incorporated into a mathematical model and independent simulations were run that showed that the experimental data were accurately predicted by the mathematical model. Thus, this study indicated that basement membranes function as dynamic regulators of growth factor transport, allowing for rapid response to changing environmental conditions. The fundamental principles controlling bFGF transport through basement membrane that have been identified here might have applications in understanding how growth factor distribution is regulated throughout an organism during development and in the adult state. PMID- 9988775 TI - Activation of Rho-dependent transcription termination by NusG. Dependence on terminator location and acceleration of RNA release. AB - There is a kinetic limitation to Rho function at the first intragenic terminator in the lacZ gene (tiZ1) which can be overcome by NusG: Rho can terminate transcription with slowly moving, but not rapidly moving, RNA polymerase unless NusG is also present. Here we report further studies with two other Rho-dependent terminators that are not kinetically limited (tiZ2 and lambda tR1) which show that the requirement for NusG depends on the properties of the terminator and its location in the transcription unit. NusG is also shown to increase the rate of Rho-mediated dissociation of transcription complexes arrested at a specific termination stop point in the tiZ1 region and the rates of dissociation with three different Rho factors and two different terminators correlated with their sensitivity to RNA polymerase elongation kinetics. These results suggest a model of NusG function which involves an alteration in the susceptibility of the transcription complex to Rho action which allows termination to occur within the short kinetic window when RNA polymerase is traversing the termination region. PMID- 9988776 TI - Topology and functional domains of the yeast pore membrane protein Pom152p. AB - Integral membrane proteins associated with the nuclear pore complex (NPC) are likely to play an important role in the biogenesis of this structure. Here we have examined the functional roles of domains of the yeast pore membrane protein Pom152p in establishing its topology and its interactions with other NPC proteins. The topology of Pom152p was evaluated by alkaline extraction, protease protection, and endoglycosidase H sensitivity assays. The results of these experiments suggest that Pom152p contains a single transmembrane segment with its N terminus (amino acid residues 1-175) extending into the nuclear pore and its C terminus (amino acid residues 196-1337) positioned in the lumen of the nuclear envelope. The functional role of these different domains was investigated in mutants that are dependent on Pom152p for viability. The requirement for Pom152p in strains containing mutations allelic to the NPC protein genes NIC96 and NUP59 could be alleviated by Pom152p's N terminus, independent of its integration into the membrane. However, complementation of a mutation in NUP170 required both the N terminus and the transmembrane segment. Furthermore, mutations in NUP188 were rescued only by full-length Pom152p, suggesting that the lumenal structures play an important role in the function of pore-side NPC structures. PMID- 9988777 TI - To suppress is human, to disclaim divine. PMID- 9988778 TI - Supplements facts versus all the facts. What the new label does and doesn't disclose. PMID- 9988779 TI - Ipriflavone: an important bone-building isoflavone. AB - Ipriflavone, an isoflavone synthesized from the soy isoflavone daidzein, holds great promise in the prevention and treatment of osteoporosis and other metabolic bone diseases. It has been widely studied in humans and found effective for inhibiting bone resorption and enhancing bone formation, the net result being an increase in bone density and a decrease in fracture rates in osteoporotic women. While ipriflavone appears to enhance estrogen's effect, it does not possess intrinsic estrogenic activity, making it an attractive adjunct or alternative to conventional hormone replacement therapy. Preliminary studies have also found ipriflavone effective in preventing bone loss associated with chronic steroid use, immobility, ovariectomy, renal osteodystrophy, and gonadotrophin hormone releasing hormone agonists. In addition, it holds promise for the treatment of other metabolic diseases affecting the bones, including Paget's disease of the bone, hyperparathyroidism, and tinnitus caused by otosclerosis. PMID- 9988780 TI - A cross-over study of the effect of a single oral feeding of medium chain triglyceride oil vs. canola oil on post-ingestion plasma triglyceride levels in healthy men. AB - Due to its unique absorption and metabolism characteristics, medium chain triglyceride (MCT) oil, consisting of fatty acids with 8-12 carbons, has been used therapeutically since the 1950s in the treatment of fat malabsorption, cystic fibrosis, epilepsy, weight control, and to increase exercise performance. Medium chain triglycerides are easily hydrolyzed in the intestines and the fatty acids are transported directly to the liver via the portal venous system, in contrast to long-chain fatty acids (LCFAs), which are incorporated into chylomicrons for transport through the lymphatic system or peripheral circulation. Medium chain fatty acids (MCFAs) do not require carnitine to cross the double mitochondrial membrane of the hepatocyte, thus they quickly enter the mitochondria and undergo rapid beta-oxidation, whereas most LCFAs are packaged into triglycerides in the hepatocyte. In this single-blind, randomized, cross over study, 20 healthy men ingested a single dose of either 71 g of MCT oil or canola oil. Blood samples were taken at baseline and at hours one through five post-ingestion to compare the effect of a single oral dosing of MCT oil versus canola oil on post-ingestion plasma triglyceride levels. Mean triglyceride values after canola oil increased 47 percent above baseline (p <0.001), while mean triglyceride values after MCT oil decreased 15 percent from baseline (p <0.001), which is consistent with several other studies involving short- and longer-term feeding with MCT oil. The effect of long-term usage of MCT oil on triglycerides is yet to be established. PMID- 9988781 TI - Squalene and its potential clinical uses. AB - Squalene, an isoprenoid compound structurally similar to beta-carotene, is an intermediate metabolite in the synthesis of cholesterol. In humans, about 60 percent of dietary squalene is absorbed. It is transported in serum generally in association with very low density lipoproteins and is distributed ubiquitously in human tissues, with the greatest concentration in the skin, where it is one of the major components of skin surface lipids. Squalene is not very susceptible to peroxidation and appears to function in the skin as a quencher of singlet oxygen, protecting human skin surface from lipid peroxidation due to exposure to UV and other sources of ionizing radiation. Supplementation of squalene to mice has resulted in marked increases in cellular and non-specific immune functions in a dose-dependent manner. Squalene may also act as a "sink" for highly lipophilic xenobiotics. Since it is a nonpolar substance, it has a higher affinity for un ionized drugs. In animals, supplementation of the diet with squalene can reduce cholesterol and triglyceride levels. In humans, squalene might be a useful addition to potentiate the effects of some cholesterol-lowering drugs. The primary therapeutic use of squalene currently is as an adjunctive therapy in a variety of cancers. Although epidemiological, experimental and animal evidence suggests anti-cancer properties, to date no human trials have been conducted to verify the role this nutrient might have in cancer therapy regimens. PMID- 9988782 TI - Evaluation of the biochemical effects of administration of intravenous nutrients using erythrocyte ATP/ADP ratios. AB - Regardless of clinical diagnosis, many acutely and chronically sick patients benefit from intravenous vitamins and minerals, which are usually administered in multiple infusions before observing obvious benefit. We hypothesized this effect was due to improved cellular energy, and attempted to find laboratory evidence via this study. Two groups of patients, chosen at random, received a single infusion of vitamins and minerals in two different dose schedules. Controls received no treatment. Study subjects were patients who presented specifically for a nutritional therapeutic approach, and although all were treated with multiple infusions, a single infusion was selected at random for this study. Thirty patients received a single infusion of a lower dose nutritional formula, sometimes known as a Myer's Cocktail (MC), and 34 had a single infusion of a higher dose nutritional I/V (NIV). Immediately prior to and after the infusion, blood was drawn and an erythrocyte ATP/ADP ratio (EADR) was determined. The results showed that in both infusion groups if the EADR was initially low, it would increase. If it were initially high, it would decrease. This effect was not observed in control subjects. Pre-test EADR boxplot analyses, derived from the results of each protocol, showed these results were statistically predictable. An analysis of variation (ANOVA) calculation indicated the differences were significant. The family error rate used was 0.05. We conclude that this regression of the EADR to the mean, as a result of either of the two infusions and not seen in control subjects, is biochemically significant. PMID- 9988783 TI - Gymnema sylvestre. PMID- 9988784 TI - Legal considerations in screening pregnant women for human immunodeficiency virus. AB - This article examines the legal implications of studies showing that the probability of maternal-to-infant human immunodeficiency virus transmission can be reduced by physician interventions. These interventions require knowledge of a pregnant woman's human immunodeficiency status. Hence the offering of human immunodeficiency virus testing has become a standard of care in pregnancy. This standard of care is examined with respect to the following: (1) the physician's legal duty to the infant, (2) negligence for failing to test, (3) liability when testing only reduces the probability of transmission, (4) damages, (5) informing women about the results of their testing, (6) protecting against liability, and (7) dealing with human immunodeficiency virus-infected pregnant women. It is concluded that the physicians are likely to have legal difficulties if a human immunodeficiency virus-infected baby is born to a woman who was not offered testing or if testing is done without documenting consent. Suggestions are made for reducing liability when testing is done, when patients refuse testing, and when one is caring for human immunodeficiency virus-infected women. PMID- 9988785 TI - Pelvic actinomycosis: a review and preliminary look at prevalence. AB - A review of the literature on pelvic actinomycosis reveals that actinomycetes normally reside in the female genital tract. Therefore the identification of actinomycetes in the vagina or cervix by any laboratory technique, including Papanicolaou smears with specific immunofluorescence or culture, is not diagnostic of any disease and is not predictive of any disease. The evidence strongly suggests that removal of the intrauterine contraceptive device of a patient with a positive culture is not necessary and that, in the absence of evidence for pelvic infection, antibiotics are not required. Pelvic actinomycosis is a rare disease whose pathogenesis is poorly understood. PMID- 9988786 TI - Laparoscopically assisted vaginal hysterectomy versus total abdominal hysterectomy: a prospective, randomized, multicenter study. AB - OBJECTIVE: The objective of this study was to evaluate short-term results of laparoscopically assisted vaginal hysterectomy with those of total abdominal hysterectomy in a prospective, randomized, multicenter study. STUDY DESIGN: One hundred sixteen patients referred for abdominal hysterectomy were randomized to either laparoscopically assisted vaginal hysterectomy (58 patients) or abdominal hysterectomy (58 patients). Inclusion criteria were one or more of the following, where a vaginal hysterectomy would be traditionally contraindicated: uterine size larger than 280 g, previous pelvic surgery, history of pelvic inflammatory disease, moderate or severe endometriosis, concomitant adnexal masses or indication for adnexectomy, and nulliparity with lack of uterine descent and limited vaginal access. An upper limit of uterine size was set at 16 weeks' gestation (ie, 700 g). RESULTS: There were no differences in terms of patient's age, parity, preoperative hemoglobin levels, mean uterine weight, and total operating time between the 2 groups. Estimated blood losses and postoperative day 1 hemoglobin drop were significantly lower for laparoscopically assisted vaginal hysterectomy than for abdominal hysterectomy (P<.05). There were 1 major and 2 minor complications in the laparoscopically assisted vaginal hysterectomy group compared with 2 major and 5 minor complications in the abdominal hysterectomy group (P not significant). Postoperative pain was lower for laparoscopically assisted vaginal hysterectomy than for abdominal hysterectomy on postoperative days 1, 2, and 3 (P<.05). Postoperative hospital stay was significantly shorter for laparoscopically assisted vaginal hysterectomy than for abdominal hysterectomy (P<.001). CONCLUSIONS: The present study demonstrates that, given adequate training in laparoscopic surgery, laparoscopically assisted vaginal hysterectomy may replace abdominal hysterectomy in most patients who require a hysterectomy and have contraindications to vaginal hysterectomy, with all the benefits associated with the vaginal route. PMID- 9988787 TI - Cold-knife conization versus conization by the loop electrosurgical excision procedure: a randomized, prospective study. AB - OBJECTIVE: Our purpose was to compare the diagnostic ability and treatment efficacy of conization by the loop electrosurgical excision procedure with cold knife conization. STUDY DESIGN: One hundred eighty women who required conization for diagnosis and treatment of cervical dysplasia or microinvasive cervical carcinoma were prospectively enrolled in a randomized clinical trial to receive either cold-knife conization or conization by the loop electrosurgical excision procedure. Conization complications, rate of lesion clearance, and therapeutic outcome were assessed for the 2 study groups. RESULTS: There were no statistically significant differences in the complication rate (P = 1.00), the rate of lesion clearance (P =.18), or the rate of disease recurrence (P =.13) between the 2 study groups. The mean follow-up was 11.2 months in the cold-knife conization group and 10.4 months in the loop-excision conization group. CONCLUSION: Cold-knife conization and loop-excision conization yield similar diagnostic and therapeutic results. PMID- 9988788 TI - Effects of hormone replacement therapy on hemostatic cardiovascular risk factors. AB - OBJECTIVES: From observational studies, there is evidence that hormone replacement therapy in postmenopausal women causes a decrease in cardiovascular events. It remains unknown, however, precisely by which mechanisms this reduction is achieved. The primary aim of this work was to study the effects of hormone replacement therapy on established hemostatic risk factors during 1-year treatment of healthy postmenopausal women. The secondary aim was to investigate whether there was any significant difference in these risk factors between hormone replacement therapy administered as a cyclic estrogen/sequential progestogen or continuous estrogen/sequential progestogen regimen. STUDY DESIGN: Sixty postmenopausal women were randomized to treatment with estradiol valerate 2 mg/day either continuously or cyclic (days 1 to 21; placebo on days 21 to 28). Both groups received cyproterone acetate 1 mg/day on days 12 to 21. Blood samples were collected before treatment and on cycle days 17 to 22 in cycles 3, 6, and 12. Thirty women with basic characteristics identical to the women included in the treatment group were included as a reference group. Blood samples were collected after 0, 6, and 12 months of observation. RESULTS: Hormone replacement therapy during 1 year caused a marginal but significant increase in plasma concentration of factor VIIc after 12 months of treatment (P <.05), a significant decrease in fibrinogen, and a significant decrease in the protein concentrations of tissue-type plasminogen activator, plasminogen activator inhibitor-1, and lipoprotein(a) after 3, 6, and 12 months of treatment (P <.05). Possible differences in the integrated response between the reference group and the hormone replacement therapy group were evaluated by comparison of the area under the curve as estimated in each individual on the basis of each analyte in the sampling periods. The area under the curve of fibrinogen was significantly lower in the hormone replacement therapy group than in the reference group (P <.03), whereas other variables did not deviate significantly between the groups. The areas under the curve did not deviate significantly between the group that received cyclic estrogen/sequential progestogen and the group that received continuous estrogen/sequential progestogen. CONCLUSIONS: One-year treatment with hormone replacement therapy influenced favorably a number of prognostic cardiovascular risk factors in healthy women. The most important effect was the lowering of fibrinogen. Furthermore, in this study the effect of hormone replacement therapy on hemostasis did not deviate between a cyclic estrogen/sequential progestogen regimen and a continuous estrogen/sequential progestogen regimen. PMID- 9988789 TI - Cervicography screening for cervical cancer among 8460 women in a high-risk population. AB - OBJECTIVE: Cervicography was evaluated as a primary screening method for cervical cancer. STUDY DESIGN: Cervigrams of 8460 women were taken on enrollment into a population-based study of cervical neoplasia. Cervicography results were compared with a referent diagnosis determined by histologic analysis and 3 cytologic tests, and with the performance of conventional cytologic evaluation. RESULTS: Cervicography identified all 11 cancers, whereas cytologic testing missed 1. Cervicography yielded sensitivities for detecting high-grade squamous intraepithelial lesions or cancer of 49.3% overall (specificity, 95.0%), 54.6% in women younger than 50 years of age, and 26.9% in women 50 years of age and older. Cytologic testing yielded sensitivities for detecting high-grade squamous intraepithelial lesions or cancer of 77.2% overall (specificity, 94. 2%), 75.5% in women younger than 50 years of age, and 84.6% in women 50 years of age and older. CONCLUSIONS: Cytologic testing performed better than cervicography for the detection of high-grade squamous intraepithelial lesions. Cervicography performed marginally better than cytologic testing for the detection of invasive cervical cancer. Cervicography is not recommended for postmenopausal women. PMID- 9988790 TI - Signs of genital prolapse in a Swedish population of women 20 to 59 years of age and possible related factors. AB - OBJECTIVE: Our objective was to study the prevalence of genital prolapse and possible related factors in a general population of women 20 to 59 years of age. STUDY DESIGN: Of 641 eligible women in a primary health care district, 487 (76%) answered a questionnaire and accepted an invitation to a gynecologic health examination. RESULTS: The prevalence of any degree of prolapse was 30.8%. Only 2% of all women had a prolapse that reached the introitus. In a set of multivariate analyses, age (P <.0001), parity (P <.0001), and pelvic floor muscle strength (P <.01)-and among parous women, the maximum birth weight (P <.01)-were significantly and independently associated with presence of prolapse, whereas the woman's weight and sustained hysterectomy were not. CONCLUSIONS: Signs of genital prolapse are frequently found in the female general population but are seldom symptomatic. Of factors associated with genital prolapse found in this study, pelvic floor muscle strength appears to be the only one that could be affected. PMID- 9988791 TI - Laterally extended endopelvic resection: surgical treatment of infrailiac pelvic wall recurrences of gynecologic malignancies. AB - OBJECTIVE: My purpose was to treat infrailiac pelvic wall recurrences of gynecologic malignancies with extended radical surgery. STUDY DESIGN: On the basis of cadaver dissection studies, I developed the laterally extended endopelvic resection techniques. The new operations were offered to patients with infrailiac sidewall disease during a 3-year feasibility study. RESULTS: Laterally extended endopelvic resections extending the lateral resection plane of pelvic exenteration to the medial aspects of the acetabulum, obturator membrane, sacrospinous ligament, and sacral plexus/piriformis muscle were performed in 18 consecutive patients. After this procedure, all patients had tumor-free intraoperative biopsy specimens taken from the remaining pelvic wall structures within the tumor bed area. The final histopathologic report confirmed clean margins in 6 patients and margins with microscopic tumor extensions only in 12 patients. Severe complications occurred in 4 patients (22%), without treatment related deaths. CONCLUSION: Laterally extended endopelvic resection allows the complete surgical removal of infrailiac pelvic-side-wall tumors, the most frequent local recurrence of lower genital tract cancer, either with free margins or with potential microscopic residual tumor as a prerequisite for combined operative and radiation treatment. PMID- 9988792 TI - Adhesion-related small-bowel obstruction after gynecologic operations. AB - OBJECTIVE: Our purpose was to evaluate a possible relationship between adhesion related small-bowel obstruction and gynecologic operations. STUDY DESIGN: The records of all female patients with the diagnosis of small-bowel obstruction from 1989 to 1996 were studied. The cause of bowel obstruction, the type and technique of previous operations, and whether the parietal peritoneum was closed at the completion of the procedure or was left open were evaluated. RESULTS: Among 262 women the most common cause of small-bowel obstruction was intra-abdominal adhesions (37.0%). Among 92 women with adhesion-related small-bowel obstruction, 35 women (38%) had undergone a previous abdominal hysterectomy. The incidence of small-bowel obstruction after an abdominal hysterectomy was 16.3 per 1000 hysterectomies. The incidence of small-bowel obstruction after cesarean delivery (5/10,000 cesarean deliveries) was significantly less than after other abdominal operations. Adhesions were found between the small bowel and the pelvis in 14 women (29.8%), and all were in women who had undergone a hysterectomy. In 33 others (70.2%) the adhesions were found between the previous abdominal incision and the intestine. The median interval between the initial operation and the small-bowel obstruction was 5.3 years. CONCLUSION: The most common cause of small bowel obstruction is postsurgical adhesions. Adhesionrelated small-bowel obstruction is commonly found after an abdominal hysterectomy. Bowel obstruction can occur many years after the initial abdominal surgery. PMID- 9988793 TI - Immunohistochemical localization of inhibin and activin subunits in human epithelial ovarian tumors. AB - OBJECTIVE: Our purpose was to examine the cellular localization of inhibin and activin subunits in human epithelial ovarian tumors. STUDY DESIGN: We examined the immunohistochemical localization of the alpha, betaA, and betaB subunits of inhibin in human mucinous and serous ovarian tumors including adenoma, cystic tumor with borderline malignancy, and adenocarcinoma. RESULTS: Immunostaining specific for the alpha, betaA, and betaB subunits of inhibin was observed in the tumor cells of the mucinous adenoma and the cystic tumor with borderline malignancy. We observed negative immunostaining specific for the alpha subunit and positive staining specific for the betaA and betaB subunits in the tumor cells of the mucinous adenocarcinoma. We did not observe any staining for the alpha subunit of inhibin in the serous tumors including benign adenoma, cystic tumor with borderline malignancy, and adenocarcinoma. However, positive staining results for the betaA and betaB subunits were observed in the serous tumor cells. CONCLUSION: Our results suggest that inhibins and activins might be secreted by the mucinous adenoma and the cystic tumor with borderline malignancy and that activins might be secreted by the mucinous adenocarcinoma and the serous tumors including benign adenoma, cystic tumor with borderline malignancy, and adenocarcinoma. PMID- 9988794 TI - Review of the granulosa-theca cell tumors from the emil Novak ovarian tumor registry. AB - OBJECTIVE: Our purpose was to review patients with granulosa and theca cell tumors as filed in the Emil Novak Ovarian Tumor Registry. STUDY DESIGN: Our study was a descriptive, retrospective study of 454 case records. RESULTS: The reviewed diagnoses were for 97 patients with granulosa cell tumors, 116 with theca cell tumors, and 97 with granulosa-theca cell tumors. The remaining cases (n = 144) were reclassified as "nonspecific" gonadal stromal tumors (n = 61), luteomas of pregnancy (n = 7), and 76 "other" cases. These included poorly differentiated cancer, metastatic cancer, mixed mesodermal tumors, and sarcomas. The tumor related mortality rate for the 310 patients with granulosa, theca, and granulosa theca cell tumors was 7% (37.3% for granulosa cell tumors only). The surgical stage of disease was the most significant prognostic factor, with a mortality rate of at least 40%, given that the tumor had spread beyond the ovary. CONCLUSION: Because the differential diagnoses of particularly granulosa cell tumors included several conditions with an extremely poor prognosis, an accurate histologic diagnosis is crucial. PMID- 9988795 TI - Telomerase activity in complete hydatidiform mole. AB - OBJECTIVE: The purpose of this study was to evaluate the association of telomerase activity in complete hydatidiform moles with subsequent development of persistent gestational trophoblastic tumor. STUDY DESIGN: By means of the standard telomerase repeat assay, we examined telomerase activity in 4 normal placentas, 31 complete hydatidiform moles (16 cases of uneventful regression, according to serum levels of beta-human chorionic gonadotropin, after evacuation and 15 cases in which persistent gestational trophoblastic disease developed after evacuation), 7 invasive moles, and 5 choriocarcinoma tissue samples. RESULTS: Telomerase activity was detected in 13 of 15 (86.7%) complete hydatidiform moles in patients who eventually underwent chemotherapy for the treatment of persistent gestational trophoblastic tumors. All 9 patients with metastatic disease (International Federation of Gynecology and Obstetrics stage III) had telomerase activity in the initial molar tissue sample. In contrast, telomerase activity was evident in only 3 of 16 (12.5%) complete hydatidiform moles from patients with spontaneous remission after evacuation (P <.05). Telomerase activity was detected in all 7 invasive moles and all 5 choriocarcinoma tissue samples but was not detected in normal placentas. CONCLUSION: The presence of telomerase activity in complete hydatidiform moles is associated with the development of persistent gestational trophoblastic tumors, such as invasive moles and choriocarcinoma. PMID- 9988796 TI - Effects of estrogen replacement therapy on plasma levels of nitric oxide in postmenopausal women. AB - OBJECTIVE: Our purpose was to assess the effects of estrogen replacement therapy on plasma levels of nitric oxide in postmenopausal women. STUDY DESIGN: The study, designed as a randomized, double-blind placebo-controlled crossover trial, involved 28 healthy postmenopausal women who had previously undergone hysterectomy. Women received either transdermal estradiol (50 g/day) (estradiol group) or placebo (placebo group) for 6 months continuously. At the end of month 6 the treatment allocations were opened, and then the treatments were exchanged for 1 month. The serum concentration of estradiol was measured at baseline before treatment and at the end of months 6 and 7. The plasma concentration of the stable oxidation products of nitric oxide was assessed before treatment and monthly until month 7. RESULTS: The mean baseline concentrations of nitric oxide metabolites in the estradiol and placebo groups were similar (mean and SD: 19+/ 4.3 vs 21+/-5.6 micromol/L, respectively). At subsequent measurements from months 1 to 6, the mean concentration of nitric oxide metabolites increased significantly in the estradiol group alone, in which the concentration ranged between 33 6.4 and 36 8.5 micromol/L. At the end of month 7 the mean level of nitric oxide metabolites in women previously treated with estradiol fell to baseline value (19 2.6 micromol/L), whereas in the placebo group the level increased significantly (34 4.4 micromol/L). CONCLUSION: Estrogen replacement therapy induces a sustained increase in plasma levels of nitric oxide in postmenopausal women; the suspension of estrogen replacement therapy is followed by a significant reduction in nitric oxide levels. The results of this study suggest that a nitric oxide-related mechanism may help to explain the cardioprotective effect of estrogen replacement therapy in the postmenopausal period. PMID- 9988797 TI - Endometrial cancer in polyps associated with tamoxifen use. AB - We report 5 cases of carcinoma arising within tamoxifen-associated endometrial polyps. In 4 of 5 cases there were no other changes within the endometrium. Given these findings, the sonohysterographic differentiation between a polypoid structure and thickened endometrium does not eliminate the need for histologic sampling of the uterine cavity. PMID- 9988798 TI - Histologic analysis of needle biopsy of urethral sphincter from women with normal and stress incontinence with comparison of electromyographic findings. AB - OBJECTIVE: Our goal was to compare urethral sphincter biopsy and needle electromyography between women who had genuine stress incontinence and those who did not. STUDY DESIGN: Seventeen continent women and 10 women with stress incontinence had urethral sphincter needle electromyography and urethral biopsy specimens blindly processed for light and electron microscopy. RESULTS: The continent group had greater skeletal muscle content and percentage in each muscle fascicle and each urethral sphincter. The group with genuine stress incontinence had higher connective tissue content. All urethral skeletal muscle was type 1. The smooth muscle was "multiunit" type and was morphologically indistinguishable between the 2 groups. On electromyography, patients with genuine stress incontinence had significantly more fibrillation potentials, fewer motor unit action potentials, a higher percentage of polyphasia, and less maximum voluntary electrical activity than control subjects. CONCLUSIONS: Women with stress incontinence differ from continent women in skeletal muscle volume, amount of fibrosis, and electromyographic parameters; these differences support a neurogenic contribution to genuine stress incontinence. Urethral sphincter has only type 1 skeletal muscle and "multiunit" type smooth muscle. PMID- 9988799 TI - Timing of labor induction after premature rupture of membranes between 32 and 36 weeks' gestation. AB - OBJECTIVE: The objective was to determine a consensus gestational age for labor induction after premature rupture of membranes between 32 and 36 weeks' gestation on the basis of the relative frequencies of adverse neonatal outcomes. STUDY DESIGN: A retrospective review was undertaken of all patients with premature rupture of membranes between 32 and 36 weeks' gestation. These patients were managed expectantly whenever possible. Neonatal outcomes were stratified by gestational age at rupture of membranes. RESULTS: Two hundred thirty-six patients with rupture of membranes between 32 and 36 weeks' gestation were managed expectantly. Prolongation of pregnancy by >/=1 week was infrequent in all cases, particularly if membrane rupture occurred after 34 weeks' gestation. Reductions in the neonatal length of stay and the incidence of hyperbilirubinemia were observed at 34 weeks' gestation with respect to younger gestational ages. No perinatal deaths occurred among the study cases. CONCLUSIONS: A "break point" in neonatal morbidity was observed at 34 weeks' gestation, which supports induction of labor at this gestational age. The short latencies observed limit the potential benefits of expectant management. PMID- 9988800 TI - Observations on labor epidural analgesia and operative delivery rates. AB - OBJECTIVE: Our purpose was to compare operative vaginal and abdominal delivery rates in a large population before and after on-demand labor epidural analgesia became available. STUDY DESIGN: We retrospectively compared patients who gave birth during a 20-month period immediately before the introduction of an on demand labor epidural analgesia service with those who gave birth during a 20 month period after the epidural usage rate had reached a plateau at approximately 60%. Operative vaginal and cesarean delivery rates were stratified according to parity and history of prior cesarean delivery. RESULTS: A total of 4859 women gave birth during the study period when on-demand epidural analgesia was available, and 4778 women gave birth in the study period before the availability of on-demand epidural analgesia. Comparisons between the women with and those without on-demand availability of epidural analgesia demonstrated no statistically significant differences in the rate of spontaneous vaginal delivery (69.5% vs 68.3%), the overall cesarean delivery rate (19.0% vs 19.4%), the primary cesarean delivery rate (13.2% vs 13.4%), or the operative vaginal delivery rate (11.1% vs 11.9%) between the 2 periods. There were no statistically significant differences in mean gestational age at the time of delivery between the 2 groups, whereas there were statistically significant increases in the proportion of nulliparous women and in mean birth weight during the on-demand epidural period. Analysis after substratification of the study groups according to parity also revealed no statistically significant differences in the primary cesarean delivery rate or the proportion of women undergoing vaginal delivery. The sample size was adequate to exclude a 2% increase in the primary cesarean delivery rate between the 2 periods with 80% power. Subgroup analysis of the population of women who gave birth while epidural analgesia was available on request demonstrated that nulliparous parturient women who requested epidural analgesia were almost twice as likely to require operative vaginal or cesarean delivery as women who did not request epidural analgesia, a finding suggesting that women who request labor epidural analgesia have an inherent propensity toward operative delivery. CONCLUSION: The introduction of an on-demand labor epidural analgesia service does not increase the rate of cesarean delivery or operative vaginal delivery. PMID- 9988801 TI - Pregnancy in patients with well-treated beta-thalassemia: outcome for mothers and newborn infants. AB - OBJECTIVE: Our purpose was to investigate the course and outcome of pregnancy in women with well-treated beta-thalassemia. STUDY DESIGN: Twenty-two pregnancies, including one twin pregnancy, in 19 women were studied. Pregnancy was advised when patients had received a prolonged intensive treatment with hypertransfusions and iron chelation and had echocardiographically normal resting left ventricular performance. All conceptions were spontaneous. Cardiac function, along with hematologic, endocrinologic, and hepatic parameters were initially assessed and monitored throughout pregnancy and for 2 to 9 years post partum. Babies were delivered by elective cesarean section. RESULTS: Twenty-one healthy newborn infants were delivered. A spontaneous abortion and a case of exomphalos also occurred. Gestation, delivery, and recovery were surprisingly uneventful, and no significant cardiac complications were encountered. CONCLUSION: Pregnancy can be safe for mothers and babies, provided that women with thalassemia have been started early on intensive treatment and have a normal resting cardiac performance. PMID- 9988802 TI - The effect of therapeutic McDonald cerclage on cervical length as assessed by transvaginal ultrasonography. AB - OBJECTIVE: Our goal was to study the effect of therapeutic McDonald cerclage on cervical length with the use of transvaginal ultrasonography. STUDY DESIGN: Cervical length was measured serially in singleton pregnancies in which there were doubts regarding cervical competence. When shortening of the cervix was substantial before 27 weeks' gestation a McDonald cerclage was applied. Wilcoxon signed rank test was used, and 1-tailed P <.05 was considered significant. RESULTS: In the 34 pregnancies studied, the mean cervical length measured at a mean gestational age of 14 weeks had decreased significantly (P <.0001) from 42 mm (95% confidence interval 38-47) to 21 mm (95% confidence interval 19-23) at a mean gestational age of 20 weeks 5 days, when a cerclage was applied. After the cerclage the mean cervical length increased significantly (P <.0001) to 34 mm (95% confidence interval 30-38) at a mean gestational age of 22 weeks 1 day (95% confidence interval 21 weeks 1 day-23 weeks 2 days). CONCLUSIONS: Therapeutic McDonald cerclage results in a longer cervical length as measured by transvaginal ultrasonography. PMID- 9988803 TI - Ketanserin versus dihydralazine in the management of severe early-onset preeclampsia: maternal outcome. AB - OBJECTIVE: An open, randomized, prospective, multicenter trial was conducted to compare the efficacy and safety of intravenous ketanserin, a selective serotonin 2 receptor blocker, with that of intravenous dihydralazine in the management of severe early-onset (<32 weeks' gestation) preeclampsia. End points of this study were blood pressure control and maternal outcome. STUDY DESIGN: Patients with a diastolic blood pressure >110 mm Hg were randomly assigned to receive either ketanserin (n = 22) or dihydralazine (n = 22) as initial therapy. Plasma volume expansion preceded antihypertensive treatment, which was administered according to a fixed schedule. RESULTS: The reductions in blood pressure with the 2 drugs were similar; however, adequate blood pressure control was reached significantly earlier with ketanserin (84 +/_ 63 vs 171 +/- 142 minutes, P = .017). Occurrence of maternal complications was significantly lower among patients who received ketanserin than among patients who received dihydralazine (n = 6 vs n = 18, P =.0007). A significant difference in favor of ketanserin was noted in daily fluid balance. CONCLUSION: Antihypertensive efficacies of ketanserin and dihydralazine were comparable, but significantly fewer maternal complications were noted among the patients receiving ketanserin. Ketanserin is an attractive alternative in the management of severe early-onset preeclampsia. PMID- 9988804 TI - Elastase activity of anaerobes isolated from amniotic fluid with preterm premature rupture of membranes. AB - OBJECTIVE: A total of 131 anaerobes isolated from amniotic fluid with preterm premature rupture of membranes and stored were examined for elastolytic activity by the method described by Williams et al (Lett Appl Microbiol 1988;7:173-6). STUDY DESIGN: Each strain was spot inoculated on a Columbia blood agar plate containing 1% solubilized elastin and incubated for 5 days under anaerobic conditions. Undigested elastin was precipitated by flooding trichloroacetic acid solution onto the plate, and a clear zone was visible as the elastolytic reaction around the spot of bacterial growth. RESULTS: Ninety-three (71.0%) of 131 organisms showed a positive elastolytic reaction. Eleven of 20 strains (55.0%) of Peptostreptococcus magnus, 9 of 18 strains (50.0%) of Peptostreptococcus micros, 12 of 12 strains (100.0%) of Fusobacterium nucleatum, 15 of 28 strains (53.6%) of Bacteroides fragilis, 8 of 15 strains (53.3%) of Bacteroides thetaiotaomicron, and 38 of 38 strains (100.0%) of Prevotella bivia were elastolytic. CONCLUSION: Anaerobic bacterial species prevalent in the normal vaginal flora that were isolated from amniotic fluid of women with preterm rupture of membranes produced elastolytic activity, plausibly inducing the destruction of host constitutive components. PMID- 9988805 TI - Relationship between myometrial resistance artery behavior and circulating lipid composition. AB - OBJECTIVES: The study investigated whether an inducible alteration in endothelium dependent relaxation in myometrial vessels could be correlated with plasma lipid composition. STUDY DESIGN: Myometrial resistance vessels were obtained from 10 women with normal pregnancy undergoing elective cesarean delivery. Paired vessels were incubated with plasma samples from patients with preeclampsia or from women with normal pregnancy and mounted on a wire myograph. After contraction with vasopressin, the degree of relaxation in response to bradykinin was observed. Plasma samples were assayed for cholesterol, triglycerides, apolipoprotein A1, and apolipoprotein B. RESULTS: A significant reduction in endothelium-dependent relaxation with respect to control values was observed in vessels incubated in plasma samples from patients with preeclampsia (P =.0001). Although no significant difference was noted between the lipid profiles of the 2 subgroups, a significant correlation was found between the vessel relaxation and the plasma content of apolipoprotein A1 (R2 = 0.36, P = .025). CONCLUSION: Plasma samples from women with pregnancies complicated by preeclampsia are capable of altering endothelium-dependent myometrial vessel relaxation. A significant relationship between the apolipoprotein A1 concentration and endothelial behavior supports the suggestion that aberrant lipid metabolism may be involved in the endothelial dysfunction characteristic of preeclampsia. PMID- 9988806 TI - Myometrial nitric oxide synthase messenger ribonucleic acid expression does not change throughout gestation or with the onset of labor. AB - OBJECTIVE: The purposes of this study were to examine expression of nitric oxide synthase isoforms in human myometrium and to determine any changes in expression with gestational age and with the onset of labor at term. STUDY DESIGN: Myometrial samples were collected from patients undergoing cesarean delivery at term before and after the onset of labor (n = 17) and throughout gestation (n = 13). Expressions of inducible, calcium-independent nitric oxide synthase and constitutive, calcium-dependent endothelial nitric oxide synthase were determined by semiquantitative reverse transcriptase-polymerase chain reaction. RESULTS: Messenger ribonucleic acid for inducible, calcium-independent nitric oxide synthase and constitutive, calcium-dependent endothelial nitric oxide synthase is expressed in human myometrium at term and throughout the second and third trimesters. Levels of messenger ribonucleic acid for both inducible, calcium independent nitric oxide synthase and constitutive, calcium-dependent endothelial nitric oxide synthase do not change with either gestational age or the onset of labor. CONCLUSION: Changes in myometrial nitric oxide synthase expression and thus of levels of endogenous nitric oxide are unlikely to be directly involved in myometrial quiescence or the onset of human parturition. PMID- 9988807 TI - Lack of local reflection of national changes in cesarean delivery rates: the Canadian experience. AB - OBJECTIVE: The purpose of this study was to determine whether national changes in cesarean delivery rates were reflected in the rates of individual maternity units. STUDY DESIGN: Cesarean delivery rate changes among the 240 largest maternity units in Canada were compared with national cesarean delivery rate changes for the years 1983 through 1992. The periods of interest for cesarean delivery rate changes were 1983 through 1988 (a period of increasing national rates), 1988 through 1992 (a period of decreasing national rates), and 1983 through 1992 (a period with similar national rates at the end points). RESULTS: For 1983-1988, 75% of the maternity units reflected changes that were not even in the same direction as those of the national mean changes. For the subperiods 1983 1992 and 1988-1992, these values were 48% and 53%, respectively. CONCLUSIONS: National trends in cesarean delivery rates do not reflect a uniform shift among maternity units, demonstrating the limitations of national means as goals for local practice. PMID- 9988808 TI - A randomized double-blind study comparing the fetal effects of sulindac to terbutaline during the management of preterm labor. AB - OBJECTIVE: The object of this study was to compare the fetal effects of sulindac and terbutaline used in the management of preterm labor on the ductus arteriosus, middle cerebral artery, renal artery, umbilical artery, fetal urine production, and amniotic fluid index. STUDY DESIGN: In a randomized, double-blind study 20 patients with preterm labor and no evidence of fetal structural anomalies or intra-amniotic infection received either sulindac (200 mg orally every 12 hours for 6 doses) or terbutaline (5 mg orally every 4 hours) for 72 hours of therapy. All medications were administered from identical blister packs. Opaque glucose base tablets were given at 4-hour intervals in the sulindac treatment arm to mimic the dosing interval in the terbutaline arm of the study. The Doppler pulsatility indices for the ductus arteriosus, middle cerebral artery, renal artery and umbilical artery and also the fetal urinary output were obtained at baseline and 5, 12, 24, 48, and 72 hours after the medication was started. Doppler data were analyzed within each group with raw data and between groups with the change in pulsatility indices from baseline. Statistical analysis was performed with the Kolmogorov-Smirnov test for normality, repeated measures analysis of variance, Mann-Whitney rank sum test, and Student t test as appropriate. P <.05 (2-tailed) was used to denote statistical significance. RESULTS: There were 10 patients in each group, with no difference in gestational age between the 2 groups (32.3 vs 31.7 weeks). Sulindac was stopped in 2 patients after severe ductal constriction was noted, in 1 at 12 hours and in the other at 24 hours. One patient at 33 weeks' gestation was delivered because of fetal distress after 46 hours of sulindac therapy. When analyzed across time within groups, the pulsatility index in the ductus arteriosus decreased significantly at 12 and 24 hours in the sulindac group but not the terbutaline group. No significant differences were noted in the middle cerebral artery, umbilical artery, renal artery, or fetal urinary output within either group over time. Significant differences in the change from baseline in pulsatility index of the ductus arteriosus between the sulindac and terbutaline groups were noted at 5, 12, 24, and 48 hours. A similar effect was noted in the change from baseline in pulsatility index of the middle cerebral artery at 48 and 72 hours. There was a significant decrease in the amniotic fluid index in both groups at 24, 48, and 72 hours. The amniotic fluid index in the sulindac group was significantly lower than that in the terbutaline group at 48 and 72 hours of therapy. CONCLUSIONS: Sulindac constricted the fetal ductus arteriosus, with an effect noted within 5 hours of starting therapy. The constriction, which resolved in all cases within 48 hours of discontinuing therapy, had minimal effects on the pulsatility index of the middle cerebral artery, renal artery, and umbilical artery. Sulindac and terbutaline both resulted in a significant reduction in the amniotic fluid index, with sulindac having a greater effect. PMID- 9988809 TI - Effects of red blood cells on the coagulation of blood in normal and preeclamptic pregnancies. AB - OBJECTIVE: The objective of this study was to determine the cellular effects of whole blood, especially of red blood cells, on the hypercoagulability of blood from patients with preeclampsia. STUDY DESIGN: The time elapsed between mixing and the onset of coagulation was measured by means of a highly sensitive rheometer for whole blood, platelet-rich plasma (in which red blood cells had been removed from whole blood), and platelet-free plasma from 3 groups of subjects: 25 nonpregnant women, 25 women with normal pregnancies, and 10 patients with preeclampsia. RESULTS: Time to coagulation for whole blood from patients with preeclampsia was significantly shorter than that for whole blood from women with normal pregnancies. However, there was no significant difference in time to coagulation for platelet-rich plasma between women with preeclampsia and those with normal pregnancies. CONCLUSION: Hypercoagulability of blood in preeclampsia appears to be strongly related to red blood cell alterations. PMID- 9988810 TI - Maternal oxygen transport variables during the third trimester of normal pregnancy. AB - OBJECTIVE: The aim of this study was to measure and calculate oxygen transport variables in uncomplicated term pregnancies. STUDY DESIGN: Ten normotensive primiparous women between 36 and 38 weeks' gestation underwent pulmonary and radial arterial catheterization as part of a larger study. Seven women had studies repeated at approximately 12 weeks post partum. Measurements were made with patients in the left lateral recumbent position after a 30-minute stabilization period. Cardiac output was measured with the thermodilution technique. Blood samples were obtained simultaneously from the pulmonary and radial arteries and analyzed in duplicate for oxygen content with a blood gas analyzer. RESULTS: The oxygen contents of both arterial and mixed venous blood are significantly lower (P <.05) in the third trimester of pregnancy (15.96 and 11.97 mL/dL, respectively) than in the postpartum period (18.00 and 13.54 mL/dL). The fall in oxygen content during pregnancy prevents any significant increase in oxygen delivery in the third trimester (867. 59 mL/min) relative to the postpartum period (806.50 mL/min, P not significant). CONCLUSION: This is the first report of directly measured oxygen transport variables in healthy pregnant women. PMID- 9988811 TI - Treatment of toxoplasmosis during pregnancy: a multicenter study of impact on fetal transmission and children's sequelae at age 1 year. AB - OBJECTIVE: Toxoplasmosis during pregnancy can cause fetal infection, with unpredictable sequelae in later life. We measured the effects of prenatal antibiotic therapy on the fetomaternal transmission of Toxoplasma gondii and on the appearance of sequelae in the congenitally infected child at age 1 year. STUDY DESIGN: In a multicenter study we investigated consecutive women with Toxoplasma seroconversion during pregnancy. Data were obtained from 144 women recruited in 5 different Toxoplasma reference centers. Through multivariate analysis we assessed the association between transmission and appearance of sequelae as a function of the following parameters: estimated gestational age at infection, administration of antibiotic therapy, duration of antibiotic therapy, and time lapse between infection and the start of antibiotic therapy. RESULTS: Sixty-four of the 144 women (44%) gave birth to a congenitally infected infant. Multivariate analysis showed that transmission was predicted neither by whether antibiotics had been administered nor by the time lapse between infection and the start of antibiotic therapy, but only by the gestational age at which maternal infection occurred (P <.0001). Sequelae were found in 19 children (13%), 9 of whom (6%) had severe sequelae. Administration of antibiotics was predictive of the absence of sequelae (P =.026, odds ratio 0.30, 95% confidence interval 0.104 0.863), in particular the absence of severe sequelae (P =.007, odds ratio 0.14, 95% confidence interval 0.036-0.584). The sooner antibiotics were given after the infection, the less frequently sequelae were seen (P =. 021). CONCLUSION: Prenatal antibiotic therapy after toxoplasmosis during pregnancy had no impact on the fetomaternal transmission rate but reduced the rate of sequelae among the infected infants. The early start of treatment resulted in a significant reduction in the number of severely affected infants. PMID- 9988812 TI - Maternal and neonatal infection rates with three different protocols for prevention of group B streptococcal disease. AB - OBJECTIVES: We compared maternal and neonatal infection rates under 3 different group B streptococcal prevention strategies and also evaluated reasons for each protocol's failures in preventing neonatal disease. STUDY DESIGN: Women who were delivered at our center from August 1, 1991, through April 30, 1998, were managed by 1 of 3 protocols for prevention of early-onset neonatal group B streptococcal infection: a selective screening protocol, The American College of Obstetricians and Gynecologists protocol, and the Centers for Disease Control and Prevention recommended universal screening strategy. We compared maternal infection rates and neonatal group B streptococcal infection rates under each protocol. We also compared reasons for each protocol's failures in preventing neonatal infection. RESULTS: Clinical chorioamnionitis rates were 7.4% with selective screening, 7.7% under The American College of Obstetricians and Gynecologists' protocol, and 5.2% with universal screening (relative risk 0.7, 95% confidence interval 0.6-0.8). Endometritis rates were 4.0% with selective screening, 4.6% with The American College of Obstetricians and Gynecologists protocol, and 2. 8% with universal screening (relative risk 0.7, 95% confidence interval 0.6-0.8). Overall neonatal group B streptococcal infection rates were lower under the 2 more recent strategies, but not significantly so. Despite the ability of universal screening to find more women at risk for group B streptococcal transmission, half of the neonatal infections under this protocol occurred when the mothers were not considered candidates for prophylaxis. CONCLUSIONS: The Centers for Disease Control and Prevention-endorsed universal screening strategy for group B streptococcal infection prevention was associated with significantly lower rates of clinical chorioamnionitis and endometritis than were the other strategies. We were unable to document statistically significant improvement in neonatal outcome under the universal screening protocol. PMID- 9988813 TI - Ultrasonographic differential diagnosis of fetal intracranial interhemispheric cysts. AB - OBJECTIVE: Ultrasonographic differentiation between intracranial supratentorial interhemispheric pathologic cystlike lesions and those related to physiologic median structures is essential because the latter have no clinical relevance, whereas the former may carry a poor prognosis. We reviewed our experience with 19 consecutive cases of interhemispheric hypoechoic lesions without parenchymal involvement diagnosed between January 1990 and June 1997 to establish their clinical significance and provide prenatal ultrasonographic criteria to distinguish between pathologic cystlike lesions and those related to physiologic midline structures. STUDY DESIGN: All patients underwent targeted prenatal scans of intracranial anatomy to establish the relationship between the fluid collections and the surrounding parenchymal and ventricular structures. In addition, a detailed anatomic survey was performed to rule out associated malformations. Follow-up, including neurologic examination, imaging, autopsy evaluation, or a combination was performed in all cases. Statistical analysis used the Wilcoxon rank sum test, the Fisher exact test, and the chi2 test for trend. P <.05 was considered significant. RESULTS: Cystlike lesions related to physiologic median structures (n = 12) included enlargement of the cavum septi pellucidi (n = 3), enlargement of the cavum vergae (n = 2), and cysts of the velum interpositum (n = 7). These lesions were unilocular and had a median size of 10 mm (range 10-30 mm); they resolved in 5 cases and remained stable in the remainder. They were not associated with overt abnormalities, other than borderline ventriculomegaly in 2 cases. Pediatric follow-up (median 26 months, range 3-84 months) showed normal neurodevelopment in all cases. Pathologic cystlike lesions (n = 7) were significantly larger (median 40 mm, range 10-80 mm, P =.004) and had a significantly worsening trend, growing more at serial prenatal ultrasonographic examinations (P =.039) than fluid collections related to physiologic median structures. Moreover, prenatal ultrasonographic evidence of associated intracranial abnormalities, in the form of partial or total agenesis of the corpus callosum and overt hydrocephalus, was present in 5 of 7 cases of pathologic cystlike lesions and in none of the 12 related to physiologic structures (P =.002). Median gestational age at diagnosis was not different between those with cystlike lesions related to physiologic median structures and those with pathologic lesions (30 and 31 weeks, respectively). Among the latter group, 1 pregnancy was voluntarily terminated, 1 infant died at 4 months of age, 2 infants had neurodevelopmental delay, and 3 infants were neurologically healthy at a mean follow-up of 43 months. Cyst shunting was necessary in 5 of 6 cases. CONCLUSIONS: Interhemispheric cystlike lesions related to physiologic structures can be prenatally distinguished from pathologic fluid collections on the basis of location, cyst size, change in size with time, and absence of associated anomalies. PMID- 9988814 TI - Differential fetal and maternal contributions to the cytokine milieu in a murine model of infection-induced preterm birth. AB - OBJECTIVE: The aim of the study was to determine the relative productions by maternal and fetal tissues of proinflammatory and anti-inflammatory cytokines in a murine model of infection-induced preterm delivery. STUDY DESIGN: The right uterine horns of CD-1 female mice at 14.5 days of a 19- to 20-day gestation were inoculated with either sterile media or live Escherichia coli. The concentrations of cytokines within uteri, placentas, membranes, and fetal lower body segments were determined by enzyme-linked immunosorbent assay at various times after inoculation. RESULTS: All infected tissues showed large, time-dependent increases in interleukin 1alpha, interleukin 1beta, and interleukin 6. These increases were maximal 13 hours after infection and were highest in uteri (15-60 times levels in uninfected tissues). Increases in tumor necrosis factor alpha and interleukin 1 receptor antagonist were much smaller (3 to 5 times) and were confined to the uterus. Although the uterus contained the greatest concentrations of interleukin 1alpha, interleukin 1beta, interleukin 6, and tumor necrosis factor alpha, fetal bodies and placentas contained the highest levels of interleukin 1 receptor antagonist. CONCLUSIONS: Time-dependent increases in maternal and fetal cytokines occurred after acute bacterial infection in this murine model. The fetus and placenta may be the most significant sources of the anti-inflammatory cytokine interleukin 1 receptor antagonist during pregnancy, whereas the uterus appears to be a more important source of interleukin 1, interleukin 6, and tumor necrosis factor alpha. Interleukin 1 receptor antagonist levels within uteri were insufficiently high to effectively inhibit interleukin 1 activity during infection. PMID- 9988815 TI - Reliability and clinical application of fetal RhD genotyping with two different fluorescent duplex polymerase chain reaction assays: three years' experience. AB - OBJECTIVE: This study was designed to evaluate accuracy and clinical usefulness of fetal RhD genotyping with fluorescent duplex polymerase chain reaction. STUDY DESIGN: Two RhD-specific gene fragments (exon 10 in polymerase chain reaction 1 and exon 7 in polymerase chain reaction 2) were amplified in samples from 213 fetuses. RESULTS: Amplification failed in 0.9% of the specimens, and equivocal results were found in 1.4% of the specimens. Of the analyses, 6.6% had to be repeated. The concordance of genotyping and serotyping was 99.0% for each polymerase chain reaction. False-positive results were noted in 4 fetuses. Concordant findings from both assays indicated the correct serotype for all fetuses. In 44 alloimmunized pregnancies, further invasive procedures were avoided for 5 of the 6 genotypically RhD-negative fetuses. Only two of 38 RhD positive fetuses had a hemoglobin level <8 g/dL at first fetal blood sampling. CONCLUSIONS: Fetal genotyping at distinct regions of the RhD gene is reliable and improves the care management of sensitized women. PMID- 9988816 TI - Diagnosis of fetal pulmonary hypoplasia by measurement of blood flow velocity waveforms of pulmonary arteries with Doppler ultrasonography. AB - OBJECTIVE: The aim of the study was to determine the utility of ultrasonographically recorded blood flow waveforms of the pulmonary artery in the diagnosis of pulmonary hypoplasia. STUDY DESIGN: The normal values of the pulsatility index and peak systolic flow of pulmonary arterial blood velocity waveforms were determined in 300 uncomplicated single fetus pregnancies with well established gestational ages between 24 and 40 weeks. We also measured the same parameters in 5 fetuses at high risk for development of severe pulmonary hypoplasia. We also determined the radial alveolar count and microvessel density, representing the extent of angiogenesis, in tissue specimens collected at autopsy from normal and hypoplastic lungs and stained both with hematoxylin and eosin and immunohistochemically for factor VIII. RESULTS: In healthy fetuses the pulsatility index values of both the right and left pulmonary arteries diminished significantly with advancing gestation, whereas the peak systolic velocity increased significantly with advancing gestation. In fetuses with pulmonary hypoplasia pulsatility index values were high and the peak systolic flow was significantly lower than in healthy fetuses. Histologic examination showed a lower radial alveolar count and poorer angiogenesis in fetuses with pulmonary hypoplasia than in healthy fetuses. CONCLUSION: Doppler ultrasonographic determination of pulmonary artery blood velocity waveforms is a useful tool for the diagnosis of pulmonary hypoplasia. PMID- 9988817 TI - Fetal supply of amino acids and amino nitrogen after maternal infusion of amino acids in pregnant sheep. AB - OBJECTIVE: The objective of the study was to determine whether a prolonged maternal infusion of amino acids would increase the umbilical uptake of amino acids and uteroplacental ammonia production. STUDY DESIGN: Six pregnant sheep (134.5 2.3 days after conception) were infused for 12 hours overnight with an amino acid solution. Uterine and umbilical blood flows were measured with the ethanol steady-state diffusion technique before (control) and during (experimental) infusion. Plasma amino acid and whole-blood ammonia concentrations were measured. RESULTS: After infusion, despite an increase in maternal arterial amino acid concentration, umbilical uptakes increased significantly only for branched-chain amino acids. Fetal ammonia concentrations and uteroplacental ammonia production increased moderately. Fetal nitrogen supply did not increase. Uterine nitrogen uptake represented 36% of the maternal nitrogen intake in the control period and 14% in the experimental period. CONCLUSION: Prolonged maternal infusion of an amino acid solution was a relatively ineffective method of increasing fetal amino acid supply. PMID- 9988818 TI - The effect of amniotic fluid on the human omental artery in vitro. AB - OBJECTIVE: The aim of the study was to determine the effect of amniotic fluid on the in vitro contractility of the human omental artery. STUDY DESIGN: Amniotic fluid and a segment of omentum were obtained from each of 5 patients at the time of planned cesarean delivery at normal term gestation for the indication of previous cesarean delivery. The omental artery was cleaned and cut into 3-mm rings, which were placed in 10-mL organ chambers for isometric tension recording. The chambers were filled with Krebs-Henseleit solution bubbled with 5% carbon dioxide in air and maintained at 37 C, pH 7.4. The rings were then equilibrated at 1 g passive tension for 90 minutes. The amniotic fluid was centrifuged for 10 minutes at 3000 rpm to remove all debris. Increasing volumes of supernatant (10 2000 microL) were added to the omental artery rings at baseline tone or after contraction with U46619 (10(-7) mol/L) or potassium chloride (60 mmol/L) to detect contractile and relaxant effects, respectively. Time-solvent control preparations were also run in parallel. RESULTS: Amniotic fluid had no effect on the basal tone of omental artery rings. Amniotic fluid had no effect on the tension in rings previously contracted with either U46619 or potassium chloride. CONCLUSIONS: Amniotic fluid has no direct effect on isolated human omental artery. The catastrophic hemodynamic changes associated with the syndrome of amniotic fluid embolism are not due to a direct effect of circulating amniotic fluid on vascular tone but rather may be due to secondary responses PMID- 9988819 TI - Heat shock protein 70 and heat shock cognate protein 70 messenger ribonucleic acid induction in the brains, hearts, and livers of neonatal rats after hypoxic stress. AB - OBJECTIVE: The aim of this study was to examine the production of 2 types of heat shock protein 70 in the organs of neonatal rats during an episode of mild hypoxic stress that was insufficient to produce histologic changes. STUDY DESIGN: Seven day-old rats were subjected to hypoxia (inspired gas of 8% oxygen and 92% nitrogen) at 33 C for 2 hours (n = 5), 3 hours (n = 5), and 4 hours (n = 5). Control rats (n = 5) inspired room air for 4 hours. The brains, hearts, and livers were removed after 4 hours of recovery. The levels of heat shock protein 70 and heat shock cognate protein 70 messenger ribonucleic acid were measured by Northern blot analysis. Arterial pH, Pao 2, PACO 2, and brain temperature were measured before, during, and at 4 hours of hypoxia in another 16 animals. Histologic examinations were carried out in these 16 animals 7 days after hypoxic stress. RESULTS: PaO 2, PACO 2, and brain temperature decreased during the hypoxic stress and returned to prehypoxic values at recovery time. Arterial pH did not change. No histologic changes were observed in any areas of the brain. Heat shock cognate protein 70 messenger ribonucleic acid was normally expressed in the brain, heart, and liver and was further induced after hypoxia in the brain and the heart. There was, however, no additional increase of heat shock cognate protein 70 messenger ribonucleic acid in the liver. there were no increments of the stress-induced form of heat shock protein 70 messenger ribonucleic acid in these organs. CONCLUSION: Mild hypoxia selectively induced messenger ribonucleic acid of heat shock cognate protein 70, which may play an important role in protecting the brain and the heart against stress. PMID- 9988820 TI - Two sinusoidal heart rate patterns in fetal lambs undergoing extracorporeal membrane oxygenation. AB - OBJECTIVES: The study analyzed the phase relationship between fetal heart rate and arterial blood pressure fluctuation during sinusoidal heart rate patterns in fetal lambs. STUDY DESIGN: Thirty-two fetal lambs were placed on extracorporeal membrane oxygenation after cesarean delivery at ages ranging between 113 and 133 days' gestation. Sinusoidal heart rate patterns persisting for >10 minutes were analyzed. The relationships between the sinusoidal heart rate cycles and the arterial blood pressure cycles were quantitatively expressed in degrees by timing the zenith and the nadir of each and assigning a phase-angle index (with 0 [360] and 180 degrees being synchronized and reciprocal, respectively). Simultaneous blood samples were taken from the 4 different sites of the fetal circulation for blood gas and acid-base analysis when the sinusoidal heart rate pattern appeared. Regional cerebral blood flow was determined by means of the colored microsphere technique in 8 fetuses with sinusoidal patterns and 7 control fetuses. RESULTS: Sinusoidal heart rate patterns were observed in 13 (40.6%) of the 32 fetal lambs. Two types of fetal heart rate and arterial blood pressure relationship could be recognized during sinusoidal pattern, the reciprocal type (n = 7) and the synchronized type (n = 9). A reciprocal type of sinusoidal pattern preceded a synchronized type pattern in 3 lambs that showed sinusoidal patterns at different stages of the experiment. The reciprocal type was associated with a higher baseline heart rate and amplitude of the sinusoidal heart rate pattern than was the synchronized type. The synchronized type was associated with a lower pH and base excess than was the reciprocal type. The cerebral blood flow in the medulla oblongata was significantly lower during the synchronized type pattern than during the reciprocal type pattern. CONCLUSION: There are 2 types of sinusoidal heart rate pattern. A synchronized type sinusoidal heart rate pattern may indicate more advanced fetal compromise than is associated with a reciprocal type pattern. PMID- 9988821 TI - Regulation of human placental chloride channel by arachidonic acid and other cis unsaturated fatty acids. AB - OBJECTIVE: Arachidonic acid has been implicated in the modulation of various transport processes, including conductive chloride transport in brush border membranes in the human placenta. The purpose of this work was to explore the effects of some cis unsaturated fatty acids on the electrophysiologic properties of the maxi chloride channels present in apical membranes from human placenta. STUDY DESIGN: Apical membrane chloride channels from human term placentas were reconstituted in giant liposomes. These cell-sized liposomes, generated by a cycle of dehydration and rehydration, are suitable for electrophysiologic studies by the patch-clamp method. RESULTS: Low micromolar concentrations of arachidonic acid reversibly inhibit maxi chloride channels in excised patches. Other cis unsaturated fatty acids, such as oleic and linoleic acids, show similar blockade. The inhibition was dose dependent. The maxi chloride channel can also be inhibited by 4,4 -diisothiocyanatostilbene-2,2 -disulfonic acid, a known chloride channel inhibitor. CONCLUSIONS: Our results identify the apical membrane maxi chloride channel as a possible electrophysi ologic counterpart of 4,4 diisothiocyanatostilbene-2, 2 -disulfonic acid and cis unsaturated fatty acid inhibited conductance previously described in brush border membranes of the human placenta. From a functional point of view the control of these channels by arachidonic acid may be of great importance in placental physiologic characteristics. Regulation of chloride channels could be important in the control of electrolyte and fluid transfer across the placenta. In addition, if these channels contribute to setting the membrane potential their regulation could have consequences for nutrient transport and delivery to the fetus. The electrophysiologic identification of these channels and their regulation might help to unravel their possible role in transplacental transport in normal and pathologic placental tissue. PMID- 9988822 TI - Stem villous arteries from the placentas of heavy smokers: functional and mechanical properties. AB - OBJECTIVE: The aim of the study was to compare the mechanical and functional properties of isolated small stem villous arteries from the placentas of women who smoked heavily (>/=15 cigarettes/d) during pregnancy with those from the placentas of nonsmokers. STUDY DESIGN: Isolated stem villous arteries were mounted in small-vessel myographs. Circumference-tension relationships were established with 124 mmol/L potassium chloride. Concentration-response curves were obtained for endothelin 1, prostaglandin F2alpha, vasoactive intestinal peptide, corticotropin-releasing hormone, sodium nitroprusside, and cadmium chloride. The effect of nitric oxide was examined with N omega-nitro-l -arginine. RESULTS: Stem villous arteries from the heavy smoking group developed a significantly lower tension than did those from nonsmokers at 6 of 9 steps of the circumference-tension experiment (P <.05). Endothelin 1 evoked a significantly greater maximum vasoconstrictive response in stem villous arteries from heavy smokers than in those from nonsmokers (P <.05). CONCLUSION: Stem villous arteries of heavy smokers have altered mechanical properties and a greater vasoconstrictive response to endothelin 1 than do those from nonsmokers. These changes may compromise fetal placental blood flow and thereby contribute to the lower birth weights seen among infants born to heavy smokers. PMID- 9988823 TI - Adding zinc to prenatal iron and folate tablets improves fetal neurobehavioral development. AB - OBJECTIVE: Our objective was to examine whether improvement in maternal zinc status during pregnancy is positively associated with fetal neurobehavioral development in a Peruvian population. STUDY DESIGN: We electronically monitored, at 32 and 36 weeks' gestation, 55 fetuses whose mothers were randomly assigned to receive, during pregnancy, a daily supplement containing 60 mg iron and 250 microg folate, with or without 15 mg zinc. Fetal heart rate and movement patterns were quantified in 55 and 34 fetuses, respectively, as indexes of neurobehavioral development. RESULTS: Fetuses of mothers who received zinc supplementation showed fewer episodes of minimal fetal heart rate variability, increased fetal heart rate range, an increased number of accelerations, an increased number of movement bouts, an increased amount of time spent moving, and an increased number of large movements. Differences by supplementation type increased with gestational age and were statistically significant at 36 weeks' gestation (P <.05). CONCLUSION: Improving maternal zinc status through prenatal supplementation may improve fetal neurobehavioral development. PMID- 9988824 TI - Nuchal thickness, urine beta-core fragment level, and maternal age for down syndrome screening. AB - OBJECTIVE: Our purpose was to report the midtrimester Down syndrome screening efficiency of a 2-analyte algorithm, urine beta-core fragment (a metabolite of human chorionic gonadotropin) and nuchal thickness, along with maternal age in a high-risk population undergoing genetic amniocentesis. METHOD: Nuchal thickness, humerus length, and maternal urine beta-core fragment levels were measured prospectively before genetic amniocentesis in 1360 singleton pregnancies, 21 (1.5%) of which had fetal Down syndrome. All analyte levels were expressed as multiples of the normal medians based on biparietal diameter. Backward-stepwise logistic regression was used to determine whether the markers were significant independent predictors of fetal Down syndrome. Matrix analysis was used to calculate an adjusted Down syndrome likelihood ratio for each patient based on the significant screening markers. Multiplication by age-related midtrimester risk gave the adjusted Down syndrome risk. The sensitivity and false-positive rates at different Down syndrome screening thresholds were used to generate a receiver-operator characteristics curve. The area under the curve was used to assess the value of this screening test. RESULTS: On the basis of logistic regression, beta-core fragment level (P 1/60 the sensitivity and false-positive rate for Down syndrome were 85.7% and 4.9%, respectively, when beta-core fragment level, nuchal thickness, and maternal age were used. Correspondence screening values at a risk threshold > 1/150 were 95.2% and 10.8%, respectively. The area under the receiver-operator characteristics curve was 0.9357 (SE = 0. 0137), indicating that the algorithm is excellent for Down syndrome screening. CONCLUSION: In this study, a combination algorithm consisting of nuchal thickness, urine beta-core fragment level, and maternal age had a high screening efficiency for Down syndrome. This algorithm should be investigated as a new option for women at high risk of having a fetus with Down syndrome. PMID- 9988825 TI - Response of obstetrics and gynecology program directors to a domestic violence lecture module. AB - OBJECTIVE: Our goal was to determine the use by obstetrics and gynecology residency program directors of The American College of Obstetricians and Gynecologists' domestic violence slide lecture module and the opinions of the directors regarding its efficacy. STUDY DESIGN: A 6-question survey was mailed to 289 directors of accredited obstetrics and gynecology programs in the United States and Canada 9 and 13 months after a learning module on domestic violence was mailed to these same persons. The questions related to receipt and use of the module in the curriculum, target audiences, future plans for integration of the module into curricula, and recommendations for future supplemental topics in the same format. RESULTS: The return rate for the survey was 57% (164/289). The responses represented university-affiliated, community- and military-based programs with representation from all geographic areas of the country. Fourteen directors who had no recollection of receiving the package were sent a second set. The lecture had been presented by 72% of the respondents' departments to audiences of residents (89%), medical students (55%), practicing physicians (41%), and the lay public (11%). Two thirds of the nonusers and 87% of the users intended to use the module as a formal lecture in the curriculum of both residents and medical students in the coming school year. Recommendations for future supplemental lecture packages included abuse during pregnancy, screening women with different cultural backgrounds, and how to ask tough questions. CONCLUSION: The majority of obstetrics and gynecology resident program directors who responded to the survey integrated or will integrate an American College of Obstetricians and Gynecologists-created learning module on domestic violence into their residents' and medical students' formal curricula. PMID- 9988826 TI - Preeclampsia: an excessive maternal inflammatory response to pregnancy. AB - The maternal syndrome of preeclampsia has previously been ascribed to generalized maternal endothelial cell dysfunction. In this review we suggest that the endothelial dysfunction is a part of a more generalized intravascular inflammatory reaction involving intravascular leukocytes as well as the clotting and complement systems. We provide evidence from our recent work and that of others that not only supports this proposal but indicates that such an inflammatory response is already well developed in normal pregnancy and that the differences between normal pregnancy and preeclampsia are less striking than those between the normal pregnant and nonpregnant states. From this we argue that preeclampsia arises when a universal maternal intravascular inflammatory response to pregnancy decompensates in particular cases, which may occur because either the stimulus or the maternal response is too strong. We conclude that there is no specific cause for the disorder, which can be better considered as the extreme end of the range of maternal adaptation to pregnancy. We propose that poor placentation is not the cause of preeclampsia but is a powerful predisposing factor. We predict that a single preeclampsia gene will not be found, nor will either a single specific predictive test or single preventive effective measure be devised. Aspects of the hypothesis are testable, and future work should allow its confirmation or refutation. PMID- 9988827 TI - Death of the papanicolaou smear? Future litigation. PMID- 9988830 TI - Causes and consequences of oral contraceptive noncompliance. AB - Compliance difficulties are more common among oral contraceptive users than is generally appreciated. Inconsistent use and method discontinuation are estimated to account for approximately 20% of the annual 3.5 million annual unintended pregnancies in the United States. In the past research focused on adolescents, for whom predictors of poor oral contraceptive compliance include multiple sex partners, low evaluation of personal health, low degree of concern about pregnancy, and previous abortion. More recent research confirms that compliance problems are common among all age groups, with 47% of women missing >/=1 pill per cycle and almost a quarter (22%) missing >/=2 pills per cycle. Good compliance has been linked to patient satisfaction with the clinician, the absence of certain side effects, establishing a regular daily routine to take oral contraceptives, and reading information distributed with oral contraceptive packaging. Clinicians are the focal point for improving oral contraceptive compliance. They should focus counseling on the transience of most side effects, instructions on dealing with a missed pill, provision of a backup method, and establishment of a daily pill-taking routine. Easy-to-understand literature should be given to patients to take home. PMID- 9988831 TI - Cycle control with oral contraceptives: A review of the literature. AB - Comparing the degree of cycle control provided by various oral contraceptives is problematic. The inherent limitations, small demonstrated differences, and differing methods of data presentation characteristic of these trials support the conclusion that it is almost impossible to compare the bleeding patterns of one preparation with those of another. Chlamydial infection, smoking, and inconsistency of use are factors that have significant effects on rates of spotting and breakthrough bleeding. Clinicians must alert patients to the possibility of intermenstrual bleeding and educate them with regard to the importance of continued, consistent oral contraceptive use to minimize those problems among pill users in their practices. PMID- 9988832 TI - Update on androgenicity. AB - The development of a new generation of progestins deemed less androgenic than their earlier counterparts has led to a number of misconceptions regarding their possible benefits in combination oral contraceptives. All combination oral contraceptives are beneficial for treating such androgenic conditions as acne and hirsutism. The only expressed androgenic effect of some first- and second generation combined oral contraceptives are changes in plasma lipid and lipoprotein levels. However, the overall effect of today's low-dose oral contraceptives is largely lipid neutral, and human and monkey studies have shown that oral contraceptive use is associated with reduced, not increased, atherosclerosis rates. Myocardial infarction rates are not increased among oral contraceptive users, except among those who are heavy smokers. PMID- 9988833 TI - Risk of venous thromboembolism with third-generation oral contraceptives: A review. AB - Recent data indicate that users of third-generation oral contraceptives, those containing the new progestins desogestrel, gestodene, and norgestimate, have 2 to 3 times the risk of venous thromboembolism faced by users of second-generation oral contraceptives. The risk of development of deep vein thrombosis was also found to be 2 to 5 times greater with a low-estrogen, desogestrel-containing oral contraceptive than with second-generation monophasic and triphasic preparations. Investigators point to an acquired resistance to the anticoagulation effects of activated protein C, the most common cause of hereditary thrombophilia, as a possible mechanism. The American College of Obstetrics and Gynecology's Committee on Gynecologic Practice reconfirms the increased risk of venous thromboembolism associated with third-generation progestins versus other progestins. Because the third-generation oral contraceptives may have benefit for some patients, however, it defers to the individual clinician's and patient's judgment regarding the use of a desogestrel-containing formulation (the only third-generation progestin available in the United States). PMID- 9988834 TI - "Estrophasic" dosing: A new concept in oral contraceptive therapy. AB - The first of a new "estrophasic" type of oral contraceptive with 20 microg ethinyl estradiol on cycle days 1 through 5, 30 microg ethinyl estradiol on days 6 through 12, and 35 microg ethinyl estradiol on days 13 through 21 and 1 mg norethindrone acetate throughout the cycle (Estrostep; Parke-Davis, Morris Plains, NJ) combines a continuous low progestin dose with a low, gradually increasing estrogen dose. It was developed to ensure good cycle control while conferring the benefits of low hormone content, such as minimizing estrogen related side effects. In a double-blind, randomized, parallel-group trial, Estrostep provided acceptable cycle control and excellent tolerableness, comparable to that of the 30-microg ethinyl estradiol monophasic control drug. In a second study Estrostep demonstrated a neutral impact on serum lipids, like the triphasic control drug. This new oral contraceptive design offers a useful low dose alternative to existing combination preparations. PMID- 9988835 TI - What are the clinical implications? PMID- 9988836 TI - Mapping of grey matter changes in schizophrenia. AB - Studies of brain changes in schizophrenia have suggested that the disorder is associated with reductions in both global and regional grey matter. In this study, we used structural neuroimaging to differentiate between these two types of change and to examine regional grey matter throughout the whole brain. Grey matter from magnetic resonance images was segmented and transformed into stereotactic space, and patients with schizophrenia and controls were compared with respect to regional grey matter (after compensating for global grey matter differences). In two preliminary analyses to test our methodology, we demonstrated that: (1) in the transformed grey matter maps, voxel values at the location of the caudate nuclei were correlated with region-of-interest measurements of caudate area in native image space, and (2) the technique detected regional grey matter changes resulting from artificial lesions created in the native images. We then used a factorial design to examine data from two studies, comprising a total of 42 schizophrenics and 52 controls. Analysis of the main effect of schizophrenia on regional grey matter revealed significant reductions in (a) the right temporal pole, insula and amygdala, (b) the left temporal pole, insula and dorsolateral prefrontal cortex. PMID- 9988837 TI - Negative symptoms of familial schizophrenia breed true in unstable (vs. stable) cerebral-ventricle pedigrees. AB - A pattern of negative symptoms associated with a high rate of ongoing brain and ventricular instability has been described in a cohort of schizophrenia spectrum probands (patients with schizophrenia, schizoaffective disorder depressed and bipolar, and psychosis NOS) (Garver, D.L., Nair, T.R., Christensen, J.D., Holcomb, J., Ramberg, J., Kingsbury, S., 1999. Differential patterns of premorbid functioning, symptoms and neuroleptic response in stable and unstable ventricular volume schizophrenia. Neuropsychopharmacology 20, in press). The present study contrasts the prevalence of negative symptoms in first- and second-degree relatives of probands with unstable ventricle volume (UnsVV) and stable ventricle volume (SVV). One hundred and sixteen first- and second-degree relatives of 10 probands were interviewed using the SANS, the 'Characterization of Course: "Pattern of Symptoms"' [from Comprehensive Assessment of Symptoms and History (CASH)], SCID and SCID-II by interviewers blind to the status of the proband. Thirty-five of the 116 family members met DSM-IV criteria for schizophrenia, SA depressed, 'Cluster A' of the SCID-II (paranoid, schizotypal, schizoid personality disorder), psychosis NOS, or psychotic affective disorder. These 35 family members were defined as falling within a 'schizophrenia spectrum' as described by Farmer, A.E., McGuffin, P., Gottesman, I.I., 1987. Arch. Gen. Psychiatry 44, 634-641, but with the addition of DSM-IV affective psychosis. On that basis, the 35 members were considered 'affected family members' (AFMs). The remaining 81 family members were considered unaffected. The 'predominant symptoms of illness' (during the past 2-3 years) for 25 of the 35 AFMs could be characterized according to the 'Patterns of Symptoms' derived from the CASH. Twenty-five of the 35 AFMs were found to maintain a predominant symptom pattern during the course of illness, which could be characterized according to the 'Pattern of Symptoms' as 'predominantly positive' or 'predominantly negative'. Three of the probands had UnsVV; seven had SVV. Of the 35 AFMs, 11 were related to the UnsVV probands, and 24 were relatives of the SVV probands. The nine rated AFMs of the UnsVV probands showed a trend toward higher SANS scores (7.3 +/- 5.1) (mean +/- s.d.) than the 20 rated AFMs of SVV probands (4.3 +/- 5.1) (p = 0.08) at the time of the interview. Eighty-three per cent (eight of 10) of rated affected pedigree members of the pedigrees delineated by probands with UnsVV probands had a predominantly negative symptom course of illness, and 96% (23 of 24) of rated affected pedigree members of the pedigrees with SVV probands had a predominantly positive symptom course of illness during the preceding 2-3 years (p = 0.002). None of the 12 rated affected pedigree members within pedigrees having UnsVV probands were married at the time of the interview; 45% (14 of 31) of affected pedigree members having SVV probands were married (p = 0.004). A psychiatric disorder, characterized by unstable cerebral ventricles and predominant negative symptoms (including avoidance/failure of marital relationships) appears symptomatically to breed true in pedigrees containing schizophrenia-like illnesses. PMID- 9988838 TI - Anticipation in schizophrenia. AB - In various genetic disorders it has been observed that the severity of illness increases and the age at onset decreases in successive generations. This phenomenon is termed anticipation. We sampled 15 families, totalling 123 individuals with at least one person affected by a disease of the schizophrenia spectrum in the index generation in each family (IG; n = 33 affected out of a total of 67 individuals) and in the parental generation (PG; n = 16 affected out of a total of 56 individuals). The pedigrees had originally been identified for linkage studies in schizophrenia. We found a significant difference between IG and PG regarding severity of illness as defined by Kendler et al's hierarchical model of categories of the schizophrenia spectrum (p = 0.001). Age at onset was significantly earlier in the IG (21.6 +/- 6.6 years) than in the PG (40.2 +/- 9.2 years) (p = 0.0001). We excluded a potential birth cohort effect by investigating a control sample consisting of two non-overlapping birth cohorts of patients with schizophrenia. Age at onset between the two groups of the control sample did not differ. Anticipation is an important aspect in the investigation of a possible genetic basis, at least for the familial form of schizophrenia. Active research on a molecular level with special emphasis on trinucleotide repeats might be able to shed further light on this phenomenon. PMID- 9988839 TI - Serotonin transporter gene is not associated with symptomatology of schizophrenia. AB - The serotonin transporter gene is a primary candidate for involvement in major psychoses. A functional polymorphism in the upstream regulatory region of the serotonin transporter gene (5-HTTLPR) has recently been reported to be associated with a variety of psychopathological conditions. In the present study, we investigated the potential influence of the 5-HTTLPR on the psychopathology of schizophrenia. One hundred and sixty-one inpatients affected by schizophrenia (DSMIII-R) were assessed by the Operational Criteria checklist for psychotic illness (OPCRIT) and were typed for their 5-HTTLPR variants by PCR techniques. Mania, Depression, Delusion and Disorganization were the four symptomatologic factors used to define phenotype. 5-HTTLPR variants were not associated with these symptomatologic factors, and consideration of possible stratification effects such as sex, and age of onset did not reveal any association either. The serotonin transporter gene is not a liability factor for the symptomatology of schizophrenia. PMID- 9988840 TI - Depressive symptoms and presynaptic dopamine function in neuroleptic-naive schizophrenia. AB - We have previously reported aberrations in the striatal presynaptic dopamine function in neuroleptic-naive schizophrenic patients compared to healthy controls (Hietala, J., Syvalahti, E., Vuorio, K. et al., 1995. Lancet 346, 1130-1131). In this extended study we explore whether the altered presynaptic dopamine function correlates with the clinical symptomatology in schizophrenia. Striatal dopamine synthesis capacity (6-[18F]fluorodopa (FDOPA) uptake, Ki values) was studied with positron emission tomography in 10 neuroleptic-naive schizophrenic patients and 13 healthy controls. The clinical symptomatology was characterized with the Positive and Negative Symptom Scale (PANSS). The patients had an increased FDOPA uptake in striatum and lacked the asymmetry in caudate FDOPA uptake (p = 0.0005), confirming our earlier results. Left striatal FDOPA uptake (Ki) values correlated negatively with depressive symptoms in a highly significant manner. On the other hand, paranoid symptomatology correlated positively with right putamen FDOPA uptake at a trend level (rho = 0.73, p < 0.02). The lack of asymmetry in caudate Ki values did not associate with any dimension of psychopathology. The major finding in this study is that depressive symptoms in neuroleptic-naive first admission schizophrenia are associated with low presynaptic dopamine function. This link appears to be hemisphere-related and may have drug-treatment implications, e.g., in prediction of response to D2 receptor blocking antipsychotic drugs. A possible connection between paranoid symptomatology and subcortical hyperdopaminergia is suggested, but this remains to be further verified. PMID- 9988841 TI - Efficacy and extrapyramidal side-effects of the new antipsychotics olanzapine, quetiapine, risperidone, and sertindole compared to conventional antipsychotics and placebo. A meta-analysis of randomized controlled trials. AB - The objective of this meta-analysis is to summarize the efficacy and tolerability of the new antipsychotics risperidone, olanzapine, sertindole and quetiapine in schizophrenia compared to placebo and conventional antipsychotics. The main results are: (1) All of the 4 new drugs are more effective than placebo, but the magnitude of the effect is only moderate [mean effect size, r, of all antipsychotics vs. placebo = 0.25, with a 95% confidence interval (CI) = 0.22 0.28, n = 2477]. (2) According to the studies published to date, sertindole and quetiapine are as effective as haloperidol, and risperidone and olanzapine are slightly more effective than haloperidol in the treatment of global schizophrenic symptomatology. (3) With respect to negative symptoms, all new antipsychotics are more effective than placebo. However, contrary to widespread opinion, so is the 'conventional' antipsychotic haloperidol. Risperidone and olanzapine are slightly superior, sertindole is as effective and--according to the only study fully published to date--quetiapine is even slightly less effective than haloperidol in this regard. (4) All new antipsychotics are associated with less frequent use of antiparkinson medication than haloperidol, with risperidone appearing to have a slightly less favourable EPS-profile than the other new antipsychotics. The methodological limitations of this review, the generalizability of the results and expectations from future research are discussed. PMID- 9988842 TI - Long-range correlations in choice sequences of schizophrenic patients. AB - Schizophrenic patients significantly greater than normals exhibit long-range correlations in sequences of choices in a simple binary choice task. Moreover, schizophrenic patients also are significantly less influenced by external stimuli than are normal comparison subjects. These effects are not significantly correlated with each other, suggesting that they do not result from a uniform attentional deficit nor are they due to simple perseverative responding or any other uniform process. The interdependence of responses over many trials suggests that the response history of many previous behavioral responses contributes significantly to the temporal architecture of schizophrenic patients. In agreement with others (Lyon et al., 1994), we find that similar organizational principles apply to physical, economical, or biological systems and seem to play an important role in human psychopathology. PMID- 9988843 TI - Convergence of cognitive and adaptive decline in late-life schizophrenia. AB - Cognitive impairment has proven to be a major predictor of overall functional deficit in schizophrenia. Despite the significant impairments seen on the part of many patients with schizophrenia that implicate decline at some point in time, there have been no longitudinal studies of adaptive decline in patients with schizophrenia. In this study, 57 geriatric patients with chronic schizophrenia were examined with measures of clinical symptoms, cognitive impairments, and adaptive functioning while living in a chronic psychiatric hospital and followed up an average of two and a half years after their referral to nursing home care. Cognitive functioning and adaptive functioning both declined over the follow-up period, whereas there was no change in schizophrenic symptoms. Changes in cognitive functioning accounted for 25% of the variance in adaptive decline, whereas the baseline severity of cognitive impairment and schizophrenia symptoms were uncorrelated with adaptive decline. These data indicate that cognitive decline may predict deterioration in overall functional status and imply that treatment of cognitive impairment might have a beneficial effect on global functional status. PMID- 9988844 TI - Episodic memory and learning in patients with chronic schizophrenia. AB - This study explored the pattern of memory functioning in 58 patients with chronic schizophrenia and compared their performance with 53 normal controls. Multiple domains of memory were assessed, including verbal and non-verbal memory span, verbal and non-verbal paired associate learning, verbal and visual long-term memory, spatial and non-spatial conditional associative learning, recognition memory and memory for temporal order. Consistent with previous studies, substantial deficits in long-term memory were observed, with relative preservation of memory span. Memory for temporal order and recognition memory was intact, although significant deficits were observed on the conditional associative learning tasks. There was no evidence of lateralized memory impairment. In these respects, the pattern of memory impairment in schizophrenia is more similar in nature to that found in patients with memory dysfunction following mesiotemporal lobe lesions, rather than that associated with focal frontal lobe damage. PMID- 9988845 TI - The long-term home-making functioning of women with schizophrenia. PMID- 9988846 TI - Neurologic signs of cerebellar and cortical sensory dysfunction in schizophrenics and their relatives. AB - Previous research has found that both schizophrenics and their relatives have significantly elevated rates of clinical neurologic signs--including 'hard' signs screened to exclude artifacts. The present study examined whether hard signs that indicate relatively localized dysfunction in particular brain regions significantly distinguish schizophrenics and/or their non-schizophrenic relatives from psychiatrically normal controls and patients with other disorders. All patients were diagnosed with DSM-III or DSM-IIIR criteria, using information from structured interviews, supplemented by chart review and family informants. Subjects were administered clinical neurologic examinations by a neurologist blind to diagnosis. The proband sample, composed of 54 schizophrenic or schizoaffective subjects, had a significantly greater proportion of subjects with signs of cerebellar dysfunction than any of the comparison samples, which included: 44 control subjects, 24 patients with substance abuse, 37 patients with bipolar disorder, and 73 of the probands' non-schizophrenic parents and adult siblings. Proportions of both probands and their relatives with signs of dysfunction of sensory cortex were significantly higher than for other groups. Cerebellar and sensory cortical dysfunctions may distinguish different subgroups of schizophrenics and may tend to reflect, respectively, non-familial and familial neuropathological factors. PMID- 9988847 TI - Clinical characteristics of schizophrenia associated with velo-cardio-facial syndrome. AB - Velo-cardio-facial syndrome (VCFS) is caused by a microdeletion in the long arm of chromosome 22 and is associated with an increased frequency of schizophrenia and bipolar mood disorder. The purpose of this study was to investigate the genetic, physical, developmental and psychiatric features of schizophrenic patients with VCFS microdeletion. It describes the clinical findings in four schizophrenic inpatients with the characteristic chromosomal deletion. The four patients displayed delayed motor development, language deficits, learning disabilities, mental retardation, early age of onset, chronic and disabling course of illness and poor response to classical neuroleptic drugs and electroconvulsive therapy. Two patients benefited from treatment with clozapine. We suggest that schizophrenic patients with a history of delayed motor development, early onset of the disorder, history of learning disability, mental retardation, congenital cardiac anomalies and/or hypernasal speech should be screened for the velo-cardio-facial syndrome deletion. The implications of this study for psychiatric phenotype, nosology, disease mechanism, and possible new treatments in the future are discussed. PMID- 9988848 TI - Schizophrenia, substance use, and brain morphology. AB - The high rate of comorbid substance abuse in schizophrenia and the consistently poor outcome of this comorbidity are well established findings in the research literature. However, the reasons for the high rate of comorbidity are not adequately understood, and the question of why some patients with schizophrenia abuse substances and others do not remains unanswered. There is widespread agreement about the clinical heterogeneity of schizophrenia, and there is some evidence suggesting that the heterogeneous clinical presentation may reflect a parallel underlying heterogeneity of brain morphology. We were interested in examining the possibility that the high rate of substance abuse and the characteristically poor outcome may be associated with the underlying brain morphology. Our hypothesis was that study subjects with schizophrenia and substance abuse would have higher rates of gross brain abnormalities than subjects with only schizophrenia. In an attempt to explore this possibility, we looked at qualitative differences in magnetic resonance imaging scans for a large sample (n = 176) of schizophrenia patients. In the group of patients who abused both alcohol and drugs, we found the rate of gross brain abnormalities to be slightly less than half the rate found among the patients with no history of alcohol or substance abuse (8 vs. 19). Although these results are not statistically significant, they reflect a trend that is compatible with previous findings, suggesting that substance abuse history may be accompanied by less impairment in certain areas, which in turn may be reflected in a better premorbid adjustment. However, our findings are not compatible with previous findings that show substance abuse to be associated with more severe symptoms and a poorer outcome in schizophrenia. PMID- 9988849 TI - Impaired sensory processing in male patients with schizophrenia: a magnetoencephalographic study of auditory mismatch detection. AB - The generation of mismatch negativity (MMN) as a component of auditory evoked event-related brain potentials has been reported previously to be severely disturbed in patients with schizophrenia. In the present study, we extended these findings to magnetoencephalography and investigated the neuromagnetic mismatch field (MMNm) in 15 male schizophrenic inpatients as compared to 16 healthy male volunteers. A standard tone of 1000 Hz and three different types of mismatch (1050-Hz tone, 5000-Hz tone, tone omission) were employed within the same paradigm, each mismatch occurring with a 10% pseudorandom probability. After correction for eye artifacts, the mean global field power of the mismatch reaction was calculated. Mismatch generation in patients with schizophrenia proved to be significantly impaired for all three conditions. This result confirms the theory of impaired auditory information processing in patients with schizophrenia at the level of the primary auditory cortex. Deficient generation of MMNm probably represents an impaired generation and/or faster decay of the sensory memory trace on the basis of disturbed sensory processing in male patients with schizophrenia. PMID- 9988850 TI - Application of cognitive scales to medical records of schizophrenia inpatients. AB - The Scales of Cognitive Impairment Rated From Institutional Records (SCIRFIR), a battery based on commonly used dementia rating instruments, was tested on the records of 26 chronically institutionalized, elderly schizophrenia patients, for the purpose of retrospectively evaluating the long-term course of cognitive change in schizophrenia and relating it to available autopsy materials. The inter rater reliability of the component scales was high (Intraclass Correlations = 0.78-0.96), the final item scores were comparable to ratings on living subjects, and Alzheimer-type neuropathological changes were associated with a markedly deteriorating course. The substantial potential of this method is discussed. PMID- 9988852 TI - Antisaccade task performance in questionnaire-identified schizotypes. AB - Individuals who scored high on Perceptual Aberration-Magical Ideation Scales (Per Mag; n = 90), the Social Anhedonia Scale (SocAnh; n = 39), and control participants (n = 89) were administered saccadic refixation (prosaccade) and saccadic suppression (antisaccade) tasks. Eye movements were scored in terms of error rates and latency. None of the groups differed in terms of their performance on the prosaccade task. Both the Per-Mag (p < 0.01) and SocAnh (p < 0.05) groups exceeded the controls in terms of mean antisaccade errors. The high risk groups did not differ from each other. Eighteen of the Per-Mag individuals and 10 of the SocAnh individuals displayed deviant antisaccade performance. These findings are particularly interesting in light of suggestive evidence that antisaccade task deficits may serve as a marker of susceptibility to schizophrenia. It is hypothesized that the individuals who scored aberrantly on the Chapman scales and displayed antisaccade performance deficits are most likely to be at risk for the development of psychosis. PMID- 9988851 TI - Mismatch negativity and N2b attenuation as an indicator for dysfunction of the preattentive and controlled processing for deviance detection in schizophrenia: a topographic event-related potential study. AB - The present study compares the amplitudes and topographic patterns of mismatch negativity (MMN) and N2b in schizophrenic patients and normal controls. Twenty one schizophrenic outpatients and 19 normal volunteers participated in the study. Event-related potentials (ERPs) were recorded in a selective attention task. During the task, subjects were required to focus on one ear, counting deviant stimuli, those deviating in duration from a sequence of standard stimuli. MMN was significantly attenuated in the schizophrenics as compared with the normals in the frontocentral regions. In addition to MMN, the N2b amplitude was also reduced, which showed a significant correlation with the MMN amplitude in the schizophrenics. The late negativity elicited by the deviant stimuli in the unattended condition showed different topographical features between the groups. Whereas the normals showed a lateralized distribution with an ear-related asymmetry, similar to that of the N2b, the schizophrenics showed a frontal dominance, coinciding with the sustained negativity reported by Naatanen et al. (1982), which reflects the automatic preparation for detecting possible subsequent stimulus changes. The amplitude of the sustained negativity was significantly correlated with the performance level in the schizophrenics. The results indicated that although both preattentive and controlled processings are impaired, schizophrenic patients, presumably due to the deficient controlled processing, owe much to automatic processing in the deviant stimulus detection process. PMID- 9988853 TI - Twelve-month outcome of patients with DSM-III-R schizoaffective disorder: comparisons to matched patients with bipolar disorder. AB - Schizoaffective disorder is a relatively common illness with an uncertain relationship with bipolar disorder. The publication of DSM-III-R in 1987 operationalized the diagnosis of schizoaffective disorder, separating it from psychotic bipolar disorder by the presence of persistent psychosis in the absence of affective symptoms. Since that time, there have been few prospective outcome studies comparing schizoaffective and bipolar disorders. The authors recruited 27 hospitalized patients with schizoaffective disorder and compared their 12-month outcome to 27 sex-, age-, socioeconomic status- and race-matched hospitalized bipolar patients. The schizoaffective patients were significantly less likely to achieve syndromic recovery than the bipolar patients, although neither group achieved high rates of symptomatic or functional recovery. As expected, the schizoaffective patients were more likely to exhibit persistent psychosis, with or without affective symptoms, throughout the follow-up interval. These data provide clinical support of the predictive value of the DSM-III-R criteria for schizoaffective disorder in a naturalistic outcome setting. PMID- 9988854 TI - Schizophrenia in Kosrae, Micronesia: prevalence, gender ratios, and clinical symptomatology. AB - The utility of genetic isolates for research is in part based on the assumption that the illness of interest is similar across cultures. In this report, we review the data on schizophrenia in Micronesia, a collection of small islands in the western Pacific Ocean. Significant variations in prevalence between the islands have been reported, as have male to female ratios which are strikingly high. We focus on the patients in Kosrae, one of the islands in the Federated States of Micronesia. Twenty-two schizophrenics are identified. We found a prevalence rate of 6.8 per 1000 and a male to female ratio of 6.3:1. Although, in many ways, the patients resemble their Western counterparts, 19 of the patients were episodically mute, especially when untreated or undermedicated. Possible explanations for this unusual symptom are discussed. PMID- 9988855 TI - Schizophrenia and seasonality of admissions: the northern Finland 1966 birth cohort study. PMID- 9988856 TI - Rationing medical care. PMID- 9988857 TI - Case of the season. Megaloblastic anemia with subacute combined degeneration (SCD) of the spinal cord. PMID- 9988858 TI - Practical approach to evaluating the fetal neural axis. PMID- 9988859 TI - The fetal genitourinary tract. PMID- 9988860 TI - Sonographic considerations with multiple gestation. AB - Determination of chorionicity is of paramount importance in risk assessment and management. Best performed in the first trimester, dichorionic placentation can be reliably assumed when the membrane is easily seen, there is a "twin peak" sign, there are clearly separate placentas, and there is discordant fetal gender. In a monochorionic twin pregnancy, there is a single placental mass, the dividing membrane is difficult to visualize until the end of the first trimester, and the membrane inserts onto the placental surface without a peaked appearance. Amniotic fluid volume assessment is important in the management of twin pregnancy. Polyhydramnios-oligohydramnios may be a manifestation of twin-twin transfusion syndrome, although oligohydramnios with normal amniotic fluid volume in the other twin's sac may more likely be a sign of velamentous cord insertion, infection, or chromosomal or structural abnormality. Fetal growth discordance is common in twin pregnancy and is associated with increased perinatal mortality and morbidity. The most sensitive indicator of discordant twin growth is thought to be estimated fetal weight, and an intertwin difference of > or = 20% is considered significant. In the clinical care of a patient with twins, it is reasonably standard to confirm chorionicity with ultrasonography in the first or early second trimester. At about 20 weeks, a level II ultrasound for anatomic survey is indicated. In dichorionic pregnancies, ultrasound examinations are then performed at 26 to 28 weeks and every 3 to 4 weeks thereafter to follow growth and amniotic fluid volume. In monochorionic twins, we generally do an additional ultrasound at about 23 to 24 weeks, because of the risk of twin-twin transfusion syndrome. In the late third trimester, careful attention should also be given to fetal position, to help with delivery planning. PMID- 9988861 TI - Sonographic assessment of the incompetent cervix during pregnancy. PMID- 9988862 TI - Prenatal magnetic resonance imaging of fetal anomalies. PMID- 9988863 TI - Magnetic resonance imaging of the fetal brain. PMID- 9988864 TI - The role of ultrasonography in fetal surgery and invasive fetal procedures. PMID- 9988865 TI - Pediatric brain tumors. AB - Pediatric brain tumors differ from adult brain tumors in several major ways. First, the types of tumors encountered in children are uncommon in adults, and vice versa. Second, tumors of the posterior fossa comprise a far greater percentage of tumors in children as compared to adults. Third, the value of extensive tumor resection, which is controversial for malignant brain tumors in adults, has been confirmed for a variety of childhood brain tumors. Fourth, chemotherapy has been shown to be effective in improving overall outcome in several childhood brain tumors, but has yet to be demonstrated to have a major benefit for adult tumors. In addition, to avoid the morbidity of irradiation on the developing nervous system, chemotherapy is increasingly used to delay or avoid using radiotherapy in children younger than 3 years of age with high-grade and incompletely resected low-grade tumors. Fifth, the prognosis for histologically similar tumors is often more favorable in children than adults. A review of general principles in the clinical presentation, diagnostic evaluation, and treatment of childhood brain tumors is followed by discussion of surgical management, adjuvant therapy, and outcome of the more common types of tumors. PMID- 9988866 TI - Current aspects of biology, risk assessment, and treatment of neuroblastoma. AB - Neuroblastoma is one of the most intensely studied solid malignancies that affect the pediatric age groups; its clinical presentation, treatment strategies and ultimate prognosis vary greatly. The biologic and genetic character of each tumor has an important impact on disease behavior, and clinical staging now incorporates these factors to generate an overall therapy plan. The clinical presentation of neuroblastoma is related to primary tumor location, production of metabolically active substances, and the presence of metastatic disease. There are also prognostically important associated syndromes including opsoclonus myoclonus, Horner's syndrome, neurofibromatosis, and a variety of other neurocristopathies. The histologic features of the tumor are of prognostic significance and are utilized in treatment stratification. The International Neuroblastoma Staging System (INSS) has unified classic clinical staging. Features at diagnosis and those determined by initial operation are combined with biologic prognostic factors to achieve risk group assignment for virtually all patients. There are groups of children in which limited therapy is curative and intermediate-risk situations where standard multimodality treatment provides favorable outcomes. Unfortunately, there are many patients with high-risk disease that require intensive strategies, but success is still limited. It is in these most resistant patients that innovative approaches are being undertaken and novel strategies are being investigated. PMID- 9988867 TI - Pediatric renal tumors. AB - A broad spectrum of renal tumors occurs in infants and children ranging from the benign cystic nephroma to the extremely aggressive malignant rhabdoid tumor of the kidney. A thorough understanding of these tumors is crucial to the optimal diagnosis and management of children with renal masses. The common renal tumors in infants and children are discussed and an orderly method for their evaluation is presented. Recent developments in the molecular biology of Wilms' tumor are outlined to provide insight into the origin of this tumor. PMID- 9988868 TI - Soft tissue sarcomas in children. AB - In childhood, soft tissue sarcomas comprise a complex group of malignancies of varied histologic subtypes, the prognoses of which depend on the histology, age, site, extent of involvement and a variety of other factors. This paper discusses the varieties of tumors classified as soft tissue sarcomas in childhood and the multimodal approach taken to cure these tumors, with particular attention to the details of difficult surgical problems. PMID- 9988869 TI - Pediatric germ cell tumors. AB - Germ cell tumors are relatively rare tumors in childhood which often present with very large tumors in both gonadal and extragonadal locations. Extragonadal tumors are more common in neonates and infants, whereas gonadal sites predominate in childhood and adolescence. Management consists of surgical resection for localized disease, chemotherapy for residual or metastatic disease, and neoadjuvant chemotherapy and delayed surgical excision for unresectable lesions. The survival for children with germ cell tumors has improved significantly over the past 2 decades with the development of platinum-based chemotherapy. Mature and immature teratomas at any site, and completely resected (Stage I) malignant gonadal and extragonadal tumors, are treated with surgical excision and observation. Malignant lesions with microscopic residual, lymph node disease, or metastatic disease receive platinum-based chemotherapy. Current survival for low stage (Stages I and II) gonadal sites approaches 100% and survival for higher stage (Stages III and IV) gonadal sites is approximately 95%. Survival for extragonadal lesions is approximately 90% for Stages I and II and 75% for Stages III and IV. PMID- 9988870 TI - Pediatric liver tumors. AB - An infant or child who presents with a large intrahepatic mass will most likely have a malignant tumor. In children, benign tumors constitute only 30% of liver tumors and most are vascular in origin. Treatment of benign vascular tumors is conservative and seldom surgical. Hepatoblastoma is the most common malignant tumor followed by hepatocellular carcinoma. Treatment of malignant tumors is based on a combination of surgery and chemotherapy. Children with hepatic malignancies that can be resected have an excellent prognosis. Other rare benign and malignant tumors of the liver do occur and surgery plays a critical role in management. PMID- 9988871 TI - Pediatric bone tumors. AB - Although osteosarcoma and Ewing's sarcoma are quite rare, they are the only primary skeletal malignancies that occur with any regularity in children. The evaluation, diagnosis, and management of skeletal neoplasia are reviewed using these two diseases as the focus of discussion. Radiographic imaging, biopsy approaches, diagnostic considerations, and therapeutic management are explained. Demographics and pathophysiology of osteosarcoma and Ewing's sarcoma are explored in more depth. PMID- 9988872 TI - Minimally invasive surgery for solid tumors. AB - The use of minimally invasive surgery in patients with cancer is slowly evolving. There are a number of reports describing laparoscopy in adults for pancreatic, ovarian, gastric, and colon cancers. In addition, thoracoscopy has been described for lung and esophageal cancers. The role of laparoscopy and thoracoscopy in children with cancer is less clear because a number of pediatric neoplasms are sensitive to adjuvant therapy and surgery is often part of a planned multi dimensional approach. This article describes a previous reported experience with minimally invasive surgery in children with cancer, current indications for this approach, and general principles which are important regarding the operative technique. In addition, future applications for this technology are suggested. PMID- 9988873 TI - Challenge of supportive surgical care in pediatric oncology. AB - The advent of aggressive treatment protocols and the development of new techniques and procedures now require that the pediatric surgeon be an integral part of all aspects of pediatric oncology care. Supportive care issues, rather than primary tumor management decisions, now dominate the pediatric surgeon's experience and range from managing the different types of vascular access devices and their complications to assessing the surgical implications of the toxic complications of current chemotherapy protocols. New treatments such as bone marrow transplantation have presented new challenges to the pediatric surgeon, while new techniques such as minimally invasive surgery have dramatically improved our ability to render compassionate and more effective care to our patients as they undergo these potentially toxic treatment regimens. PMID- 9988874 TI - Need for inclusion and exclusion criteria for the structural abnormalities recorded in children born from exposed pregnancies. PMID- 9988875 TI - Congenital heart disease: a direct result of chromosomal duplication. PMID- 9988876 TI - What really causes FAS? PMID- 9988877 TI - High vitamin A intake in early pregnancy and major malformations: a multicenter prospective controlled study. AB - The European Network of the Teratology Information Services (ENTIS) collected and evaluated data on 423 pregnancies exposed during the first 9 weeks of gestation to a "high" dose of vitamin A (10,000 IU per day or more). Data were collected prospectively; 394 women (93.1%) were followed by telephone interview up to the first few weeks after the expected date of delivery, using standardized procedures. The presence of major structural malformations, excluding chromosomal and genetic diseases, was evaluated in 311 infants exposed to a median daily dose of vitamin A of 50,000 IU per day (range, 10,000-300,000 IU per day; interquartile range, 25,000-60,000 IU per day). Three infants with a major malformation were reported: pulmonary stenosis, stenotic anus with fistula, and bilateral inguinal hernia. No congenital malformations were reported among 120 infants exposed to more than 50,000 IU per day of vitamin A. When the birth prevalence rate of major malformations in the study group was compared with two internal control groups of infants exposed to: 1) "high" vitamin A exposure later in pregnancy, and 2) nonteratogenic agent exposures, the rate ratio was, respectively, 0.28 (CI 95% interval, 0.06, 1.23) and 0.50 (CI 95% interval, 0.14, 1.76). The studied sample did not provide evidence for an increased risk of major malformations, associated with "high" vitamin A intake during the organogenetic period, higher than 2.76 above the control reference risk of 1.91% (power 80%, alpha 0.10). PMID- 9988878 TI - Effects of prenatal cocaine exposure on embryonic expression of sonic hedgehog. AB - Cocaine use by pregnant women may adversely affect development and behavior in the exposed infants. Sonic hedgehog (shh) is a secreted protein that induces development of many structures in the embryo, including dopaminergic cells in the ventral midbrain, the limb buds, and eyes. Because prenatal cocaine exposure has been shown to adversely affect the morphogenesis of these and other systems, the present study was undertaken to test the hypothesis that maternal cocaine treatment would alter shh mRNA expression. Cocaine HCl (60 mg/kg i.p.) was administered to pregnant mice on gestational days 6-8, the time that immediately precedes the appearance of shh. Control dams received i.p. saline. Embryos from gestational days 9-11 were examined by in situ hybridization. The temporal and spatial patterns of shh expression were indistinguishable between embryos from cocaine- and saline-treated dams. Examination of forebrain, midbrain, and midbody spinal cord coronal sections failed to reveal any differences in the dorsoventral and mediolateral localization of shh. The distribution of mRNA for patched (ptc), the membrane receptor for shh, was also indistinguishable between both groups. Chick embryos were next used to examine the direct application of cocaine into the developing brain. Shh distribution was similarly unaffected in these chick embryos. These data show that maternal cocaine treatment during early neural tube development does not significantly alter the expression patterns of shh or ptc mRNA. Thus, congenital defects and behavioral abnormalities associated with maternal cocaine use do not appear to result from altered expression of the shh ptc pathway. PMID- 9988879 TI - Increased incidence of renal anomalies in patients with chromosome 22q11 microdeletion. AB - A well-known association exists between the presence of a chromosome 22q11 micro deletion and conotruncal heart malformations. Recently, there has been an increased appreciation of the expanded clinical phenotype associated with this chromosome abnormality. We performed a medical record review to evaluate the incidence of renal anomalies in a group of 15 patients ascertained in a single medical center over a 33-month period. Of the 15 patients, 13 had a renal sonogram performed. Five of 13 patients studied (38.4%) had a renal anomaly. The specific abnormalities identified included: bilateral duplex kidneys (1 patient), unilateral renal agenesis (1 patient), unilateral multicystic dysplastic kidneys (2 patients, including 1 ascertained prenatally), and bilateral, extremely small (less than 2 SD below mean) kidneys (1 patient). The incidence of renal anomalies in our patient population (38.4%) was higher than expected, and agrees with a recent European collaborative study. The present report and the European study both demonstrate a higher percentage of renal abnormalities than the 10% previously reported in the literature. Because patients affected with chromosome 22q11 micro-deletion often have multiple medical and surgical problems, we recommend obtaining a baseline renal ultrasound examination to identify renal anomalies before they become symptomatic. PMID- 9988880 TI - Phenytoin-induced alterations in craniofacial gene expression. AB - In utero exposure to the anticonvulsant drug phenytoin has been shown to alter normal embryonic development, leading to a pattern of dysmorphogenesis known as the Fetal Hydantoin Syndrome. This embryopathy is characterized by growth retardation, microcephaly, mental deficiency, and craniofacial malformations, although the precise mechanism(s) by which phenytoin alters normal developmental pathways remains unknown. To better understand the molecular events involved in the pathogenesis of phenytoin-induced congenital defects, alterations in gene expression were examined during critical periods of craniofacial development. Pregnant SWV mice were administered phenytoin (60 mg/kg/day) from gestational day 6.5 until they were sacrificed at selected developmental time points. Tissue from the craniofacial region of control and exposed embryos was isolated, and samples were subjected to in situ transcription, antisense RNA amplification, and hybridization on reverse Northern blots to quantitatively assess expression of 36 candidate genes. Chronic phenytoin exposure significantly altered expression of several genes at distinct times during morphogenesis. Results of these studies show that expression of the retinoic acid receptors (RAR) alpha, beta, and gamma were significantly increased by phenytoin exposure. Elevations in gene expression of laminin beta 1, and the growth factors IGF-2, TGF alpha, and TGF beta 1, were also demonstrated in the craniofacial region of phenytoin-exposed embryos. As several of these genes are transcriptionally regulated by retinoic-acid responsive elements in their promoter regions, phenytoin-induced alterations in expression of the RAR isoforms may have severe downstream consequences in the regulation of events necessary for normal craniofacial development. Such alterations occurring coordinately at critical times during craniofacial development may account for the dysmorphogenesis often associated with phenytoin exposure. PMID- 9988881 TI - Smoking during pregnancy and Poland sequence: results of a population-based registry and a case-control registry. AB - As Poland sequence (PS) could have a vascular disruptive origin, here we analyzed the possible relationship between maternal smoking during pregnancy and PS, using data from two registries with different methodologies: the Hungarian Congenital Abnormality Registry (HCAR), which is a population-based registry, and the Spanish Collaborative Study of Congenital Malformations (ECEMC), which is a hospital-based and case-control study. The results presented here in a multivariate analysis, although based on a small sample size, suggest that maternal smoking during pregnancy may increase the risk for PS by about 2-fold. This result was similar in the two studied programs with different methodologies and different uncontrolled confounding factors. However, as this is the first time that PS has been associated with maternal smoking during pregnancy, further analyses are needed to confirm our findings. PMID- 9988882 TI - Candidate genes for nonsyndromic cleft lip and palate and maternal cigarette smoking and alcohol consumption: evaluation of genotype-environment interactions from a population-based case-control study of orofacial clefts. AB - Previous studies suggest that the relationship between genes and nonsyndromic cleft lip +/- cleft palate (CLP) or cleft palate only (CP) may be modified by the environment. Using data from a population-based case-control study, we examined allelic variants for three genes, i.e., transforming growth factor alpha (TGFA), transforming growth factor beta 3 (TGFB3), and Msh (Drosophila) homeobox homolog 1 (MSX1), and their interactions with two exposures during pregnancy (maternal cigarette smoking and alcohol consumption) as risk factors for CLP and CP. For each cleft phenotype, risk estimates associated with most allelic variants tended to be near unity. Risk estimates for maternal smoking (> or = 10 cigarettes/day) were significantly elevated for CP and were most elevated among infants with allelic variants at the TGFB3 or MSX1 sites. By comparison, risk estimates for maternal alcohol consumption (> or = 4 drinks/month) were significantly elevated for CLP and were most elevated among infants with allelic variants at the MSX1 site. Our results suggest that development of CLP and CP may be influenced independently by maternal exposures but more significantly by interaction of such exposures and specific allelic variants. PMID- 9988883 TI - Developmental toxicity and toxicokinetics of two endothelin receptor antagonists in rats and rabbits. AB - Embryo-fetal development studies with toxicokinetic evaluations were conducted in rats and rabbits after oral or intravenous administration of two endothelin receptor antagonists. In the rat studies, females were administered SB-217242 (0.01-300 mg/kg/day) orally or SB-209670 (0.01-50 mg/kg/day) intravenously from days 6-17 postcoitus (pc). External and visceral fetal examinations were performed at necropsy on day 21 pc. Maternal body weight and food consumption were decreased only at 300 mg/kg/day SB-217242. Embryolethality was seen at 300 mg/kg/day SB-217242. Decreased fetal body weight occurred at 300 mg/kg/day SB 217242 and 50 mg/kg/day SB-209670. Dose-dependent increases in the mean percentage of fetuses per litter with malformations were seen at > or = 50 mg/kg/day SB-217242 and > or = 10 mg/kg/day SB-209670. Craniofacial, great vessel, heart, and thyroid were the predominant malformations. In the rabbit studies, females were administered SB-217242 (0.01-50 mg/kg/day) orally or SB 209670 (0.01-25 mg/kg/day) intravenously from days 6-20 pc. There was no drug related effect on maternal body weight or food consumption. Embryolethality was observed at 50 mg/kg/day of SB-217242. Dose-related increases in the mean percentage of fetuses per litter with malformations were seen at > or = 10 mg/kg/day SB-217242 and > or = 10 mg/kg/day SB-209670. The malformations were similar to those observed in the rat studies, except that craniofacial development was not altered by SB-209670. The malformations observed are consistent with the pattern of endothelin-1 gene expression described in mouse embryonic pharyngeal arches and heart, and with the craniofacial and cardiovascular malformations observed in endothelin-1-deficient mice. Given the known role for endothelins in development, and concordant malformations in rats and rabbits observed in this study, teratogenicity is likely to be a class effect of endothelin receptor antagonists. PMID- 9988884 TI - [Surgery of the base of the skull]. AB - To treat pathological processes, primarily tumors, in the base of the skull is one of the most intricate neurosurgical problems. In the past decade, interest in this problem has greatly increased due to the advent of new methods of diagnosis, up-to-date neurosurgical equipment and to a greater cooperation of physicians of related disciplines: ophthalmologists, otosurgeons, plastic surgeons. The authors present and summarize the experience accumulated by the researchers of the N. N. Burdenko Institute of Neurosurgery in the past 10 years in treating basal tumors. Based on a great deal of clinical findings, approaches are proposed in treating some groups of basal tumors, such and pituitary adenomas, craniopharyngiomas, meningiomas at various sites, trigeminal and acoustic neurinomas, and malignant neoplasms of the base of the skull. The conditions required for successful surgical treatment of the processes in the base of the skull are described in detail. One of them is a correct determination of a surgical approach. PMID- 9988885 TI - [The use of the contralateral pterional approach in the surgery of cerebral aneurysms]. AB - The contralateral pterional approach was used in the surgical treatment of 17 patients with cerebral aneurysms. Six of them had solitary aneurysms in the ophthalmological segment and fork of the carotid artery, the aneurysms were clipped by the contralateral approach. Eleven patients were found to have multiple aneurysms in different carotid beds and the main artery, the aneurysms were clipped from blood flow by applying the pterional approach, including the contralateral one. The contralateral pterional approach may be the method of choice in surgery for cerebral aneurysms. PMID- 9988886 TI - [The clinico-neuropsychological aspects of arteriovenous malformations of the hippocampus]. AB - A comprehensive examination was made in 39 patients with arteriovenous malformations (AVM) of hippocampus. Prior to and following surgery, all the patients underwent neuropsychological study after A. R. Luriia (1962). Mnestic disorder was found to be the most common abnormality in patients with AVM at this site. Before surgery, they were detected in 34 of 39 patients, 11 of them having severe memory disorders with the traits of the Korsakoff's syndrome. These patients were found to have mixed posthemorrhagic lesion of the hippocampus, other portions of the temporal lobe and periventricular structures. Twenty nine patients were operated on, 14 of them had progressive mnestic disorder of the modally nonspecific type irrespective the side operated on. There were no postoperative Korsakoff's syndromes. There was no progression in memory defects in patients after surgery on the brain drastically changed after hemorrhage or removal of minor malformations. Before hemorrhage, epileptic paroxysms were observed in 2 of the 39 patients only in the presence of massive AVM obligatorily involving the temporal cortex. Following surgery, there were no new epileptic paroxysms and changes in the emotional status and motivations in the patients. Thus, the hippocampal formation is involved in the primary mechanisms of fixation, retention, reproduction of a memory trace. The participation of many structures of the brain is required to form an emotional status, motivation, and clinical manifestations of epileptic activity. PMID- 9988887 TI - [The surgical results in patients with different forms of torsion dystonia]. AB - The paper describes stereotactic operations made in 278 patients with different forms of torsion dystonia during 20 years. Late outcomes were studied and assessed in 130 patients. The duration of follow-ups was 3 to 23 years. The patients' mean age at surgery was 30.5 years. The indications for surgical treatment were ineffective medical treatment and progressive disease. Positive early and late postoperative outcomes were achieved in 93 and 70% of patients, respectively. Complications developed in 3.2 and 12.3% of patients after the first and second operations, respectively. The positive outcome depends on the form, etiology, the destructible structure or a complex of structures. Surgical treatment of patients with torsion dystonia by stereotactic operations on basal ganglia is an effective treatment that provides a steady-state positive result in 70% of patients in the late period. PMID- 9988889 TI - [The effect of experimental craniocerebral trauma on cell-mediated and humoral immunity reactions]. AB - Brain injury (BI) was induced in 9 rabbits either after cranial trepanation or through graded blow. Cell-mediated immunity to brain autoantigens in the automix culture test and the production of specific antibodies on soluble protein antigen immunization were studied. Experiment BI was not found to result in the emergence of the lymphocytes capable of mediate cellular autoimmune responses. However, there were increases in the nonspecific lymphocytic sensitivity to the T lymphocytic mitogen ConA and in a humoral immune response, suggesting the activation of T- and B-cell immunity following BI. PMID- 9988888 TI - [Free-radical and neuroimmune processes in primary and repeated craniocerebral trauma (in an experiment)]. AB - The impact of primary and repeated brain injury (BI) (moderate contusion of the brain) on changes of pro- and antioxidative processes in the brain and blood, as well as on the body's neuroimmune responses during 30 days following injury were studied in an experiment on albino rats. The changes in the rate of lipid peroxidation (LPO) were shown to be significantly higher in repeated BI than in primary one. There was no correlation between the changes in the rate of LPO in the blood and in the brain tissue. Immune disorders, namely: the proliferative activity of T and B lymphocytes were slightly milder than in primary BI while in repeated BI, neurosensitization was detectable earlier, which was more pronounced. Thus, goal-oriented correction of free radical processes should be made in the brain and of neuroimmune disorders in BI. PMID- 9988890 TI - [The assessment of the dynamics of somatosensory evoked potentials in the surgical and conservative treatment of patients following spinal and spinal cord trauma]. AB - Somatosensory evoked potentials at the cortical and spinal levels were dynamically studied in patients with vertebral column and spinal cord injuries before and after radical reparative surgery. The study showed that quantitative determination of the time course of changes occurring was highly effective in neurological disorders. Most significant were changes in the latent periods and amplitude of the peaks N11, N13, N20, P23 in the activation of n. medianus and N21, N28, P37, N45 in the bilateral stimulation of n. tibialis posterior. There was a correlation of neurophysiological and clinical manifestations in 50-60% of cases. Thus, the neurophysiological studies quantitatively verify the efficiency of surgical treatment for vertebral column and spinal cord injuries. PMID- 9988891 TI - [The morphological basis for using low-intensity laser radiation in patients with foci of spinal cord contusion]. PMID- 9988892 TI - [The cerebral hyperperfusion syndrome after a carotid endarterectomy operation (a case report and review of the literature)]. AB - The paper describes a clinical case of the cerebral hyperperfusion syndrome, a rare complication of carotid endarterectomy. The syndrome appeared as the generalized convulsive syndrome in the patient in the early postoperative period. In the context of clinical observation, the results of analysis of the literature are presented and the pathogenesis, diagnosis, therapy, and prevention of the cerebral hyperperfusion syndrome considered. PMID- 9988893 TI - [The molecular genetics of gliomas and the outlook for molecular neurosurgery]. PMID- 9988894 TI - [The use of the temporal muscle for closing postoperative wounds]. AB - The correct use of the musculus temporalis may close rather extensive defects of the base of the skull, yielding good functional and cosmetic results. For plastic purposes, the following types of a graft of the musculus temporalis are applied: 1) a simple interpolated graft; 2) a split-thickness interpolated graft; and 3) a free graft (by crossing the tendon of the musculus temporalis, which allows the muscle to be additionally displaced) for closure of defects after removal of tumors from the socket, maxillary, sphenoidal sinuses, infratemporal fossa, the bases of the middle cranial fossa, for plastic repair of the hard palate, for closure a defect after transpyramidal access (mastoidectomy) and for the treatment of ankylosis of the mandibular joint. Axial grafts may be used to repair the scalp and supercilia. PMID- 9988895 TI - Ways and side tracks in research of rheumatic diseases. PMID- 9988896 TI - Psoriasis--a dermatological enigma. AB - At the beginning, the interdisciplinary character of psoriasis encroaching into numerous fields of medicine as well as non-medical sciences is emphasized. The disease has been found an interesting field for genetic studies, also entering the fields of endocrinology and pathophysiology, and as a psychosomatic phenomenon arising many questions in the domain of psychiatry and psychology. With the associated joint and bone alterations, psoriasis is an intriguing problem for an array of medical disciplines, e.g., rheumatology, orthopedics, physical medicine and balneology. Pediatrics is involved through psoriasis in children, and ophthalmology through ocular symptoms of the disease. The therapeutic use of ultraviolet rays introduces psoriasis in the field of photobiology, and the impact of diet into the domain of dietetics. Also, alternative medicine is involved to a greater extent in psoriasis than in any other disease. This survey is followed by a historical account of psoriasis, revealing that the disease was known in all periods of the development of mankind that have left written documents behind. However, it was only toward the end of the 18th century and at the beginning of the 19th century that psoriasis was recognized and described as a unique and independent disease. The prevalence of psoriasis in Europe und USA ranges between 1.5%-2% and 0.5%-1.5%, respectively. The disease is rare in blacks, Indians and yellow race, whereas in Eskimos it is not found at all. Then, psoriasis is presented as a hereditary disease, the onset of which requires the action of so-called provocative factors triggering the hereditary elements. Psoriasis most commonly develops at the age of 20-50 years, i.e. during the most active period of man's life. Then, the morphological classification of psoriasis according to clinical picture is presented, with a historical account of pathophysiologic and etiologic concepts over the past hundred years. And finally, the basic trends and concepts of the treatment of psoriasis are described, with special reference to the fact that it should be considered a skill rather than a schematic procedure. The possibilities and value of preventive measures, emphasizing the role of patient health education in the complex treatment of the disease, are presented. PMID- 9988897 TI - Values of complement, T- and B-lymphocytes and immune complexes in patients with skin allergies. AB - The aim of this pilot study was to determine the values of total complement, C3 and C4 fractions, C1-esterase inhibitor, T- and B-lymphocytes, and immune complexes in our patients with skin allergic disease. The purpose was to investigate the probability of type III hypersensitivity reaction in the development and onset of skin allergies. The values of these parameters were determined in ten patients with atopic dermatitis and ten patients with chronic allergic urticaria. Results showed most of the study subjects with atopic dermatitis (7/10) to have increased CH50 values, a finding not observed in the patients with chronic allergic urticaria (2/10) and healthy controls (0/10). No major changes in other parameteres were found in any of the patient groups. A statistically significant difference (p < 0.05) was found among the three groups in CH50 and C4 values. PMID- 9988898 TI - Omeprazole, azithromycin and amoxicillin or amoxicillin plus clavulanic acid in eradication of Helicobacter pylori in duodenal ulcer disease. AB - Treatment with omeprazole (OME), azithromycin (AZI) and amoxicillin (AMO) resulted in encouraging Helicobacter pylori cure rates in pilot and control studies. The aim of this study was to establish whether OME + AZI in combination with either AMO or ACA (amoxicillin plus clavulanic acid) are effective in curing H. pylori infection. A hundred patients with active duodenal ulcer and H. pylori infection were treated with OME (day 1-10: 2 x 40 mg/day, day 11-24: 40 mg/day, day 25-42: 20 mg/day) plus AZI 500 mg/day for the first 6 days. Patients were randomly assigned to either AMO 2 x 1000 mg/day (group A, n = 50) or ACA 2 x 1250 mg/day (group B, n = 50) during the first 10 days of treatment. H. pylori status was determined by urease test and histology before and 6 weeks after completion of therapy. Ninety-five patients completed the study. H. pylori infection was eradicated in 85.4% (41/48) patients from group A (intention-to-treat (ITT) analysis: 82%) versus 91.5% (43/47) patients from group B (ITT) analysis: 86%) (NS). All ulcer had healed after 42 days of omeprazole treatment. Side effects, usually minor, were recorded in 12.5% (group A) and 14.9% (group B) of patients (NS). Therapy had to be discontinued in two patients (one in group A and one group B) only. Ten-days treatment with OME and AZI (for the first 6 days) with AMO or ACA are simple and highly effective regimens to cure H. pylori infection in patients with duodenal ulcer disease. PMID- 9988899 TI - Changes in skeletal metabolism in pubertal girls can be revealed by biochemical parameters of calcium metabolism and bone turnover. AB - Biochemical changes related to skeletal turnover in puberty were investigated in a sample of 67 girls aged 8-14 years. The following biochemical parameters were measured in serum: total calcium, phosphate, magnesium, total alkaline phosphatase, osteocalcin, and calcium and hydroxyproline in the second morning urine. Thirty-five premenarchal girls (8-11 years) had significantly lower serum calcium, and higher alkaline phosphatase and phosphate than those menstruating regularly (N = 32, 12-14 years). A statistically significant negative correlation of serum parameters and age was found for phosphate and alkaline phosphatase in all subjects, and for calcium and magnesium only in the premenarchal girls. These results indicated the more intensive processes of skeletal metabolism occurring in prepubertal age and early puberty to reflect in basic biochemical parameters of calcium and bone metabolism. Analysis of correlation between biochemical parameters showed alkaline phosphatase and phosphate to correlate positively with hydroxyproline excretion and negatively with urinary calcium in all subjects. In the subjects after menarche, osteocalcin correlated with alkaline phosphatase and phosphate. Thus, biochemical parameters indirectly reflected physiologic changes occurring with bone turnover in puberty. Variations in bone turnover during puberty, including a more pronounced bone formation during prepubertal or early stages, can be indirectly observed through biochemical parameters related to calcium and bone metabolism. Investigations of skeletal growth and puberty would benefit from specific markers of bone remodeling and "basic" biochemical parameters, as it might disclose subtle metabolic relationships. PMID- 9988900 TI - Intraocular pressure and visual field defects. AB - During a five-year study period, therapeutic levels of intraocular pressure (IOP) and visual field defects were assessed in 108 patients with open-angle glaucoma. In a group of 53 glaucoma patients with non-progressive visual field changes (mean age 65.2 +/- 6.3 years), the IOP level was 15.8 +/- 2.6 mm Hg, whereas in a group of 58 patients with progressive visual field changes (mean age 68.7 +/- 8.3 years) the IOP level was 19.9 +/- 2.9 mm Hg. Study results suggested that preservation of the visual field in glaucoma patients requires therapeutic IOP levels of < 16 mm Hg. PMID- 9988901 TI - Croatian blood transfusion service in prevention of HIV spread during the war. AB - Beside the war, an unfavorable epidemiological situation and a large number of foreign peace troops that entered the country without having been previously tested for infectious diseases, the number of AIDS cases in our country remained relatively low. The transfusion service played a considerable part in the prevention of HIV infection spread. Although the blood transfusion service was faced with higher demands for blood and blood products, throughout the period of the war not a single blood unit was imported and no single unit of blood components was transfused without having been previously tested for the presence of viral disease markers. Despite enormous economic difficulties, three new diagnostic tests were then introduced in our transfusion practice as a regular procedure: anti-HCV in 1993, anti-HIV 2 in 1994 and anti-HIV 1/0 in 1995. PMID- 9988902 TI - Lingual thyroid. AB - Lingual thyroid is one of the rarest anomalies of thyroid origin. It is located in the midline of the base of the tongue. Lingual thyroid represents ectopic, i.e. accessory thyroid tissue. It develops from the epithelium of the thyroglossal duct that has not obliterated properly, and it is sometimes the only thyroid tissue. Beside two cases presented, the embryology, symptomatology, diagnostic and therapeutic procedures, the literature reports of lingual thyroid are reviewed. PMID- 9988903 TI - Immunity of the Croatian population to poliomyelitis--a serosurvey. AB - Eight years after the last case of poliomyelitis it was of a special interest to determine the immunity level of the Croatian population to polio and thus to evaluate the possible risk of the revival of this infection. For this purpose, 200 sera samples were collected from individuals of different age and place of residence. Neutralizing antibodies (NT) for all three polioviruses were searched for. Antibody titers of > or = 1:8 were considered positive. Results of the study showed some 75% of the study subjects to have antibodies to polio type 1 and 2, and some 83% to type 3. Only 4% of the sera tested had no NT antibodies to any of the three types. The lowest mean geometric antibody titer (GMT) was for polio type 3 (GMT3 = 19.4; reciprocal value) and somewhat higher for type 1 (GMT1 = 23.5) and type 2 (GMT2 = 22.6). When the antibody titers were related with the age of the subjects, they were found not to decline with age, which was ascribed to periodical boosters with vaccinal strains. It is stressed that, in spite of the eradication of poliomyelitis achieved in Croatia, compulsory vaccination of the children should be continued until its global eradication. PMID- 9988904 TI - Glaucoma simplex congenitum in the Veli Brgud village, the Opatija County, Republic of Croatia--a genealogical nine-generation study. AB - On the Ucka hill-side, in the Veli Brgud village, Opatija County, Istrian peninsula, Republic of Croatia, there is a great number of patients with glaucoma simplex congenitum (open angle glaucoma) among a total of 550 Croatian inhabitants. Of these, 536 (97.5%) were ophthalmologically examined and glaucoma simplex congenitum was diagnosed in 74 persons, some of them already blind. The proportion of the affected was 13.8%. The cases were largely from the Afric family (nicknamed "Sor"). The pedigree of the Afric-"Sor" family has 1215 members through nine generations, descendants of Matheus Afric (1762) and Marija Bratovic (1765). In the total of 536 examined, 291 (54%) belong to this pedigree, whereas 67 (90%) out of 74 affected persons were of the same pedigree. The rest of 7 (9.46%) affected patients did not descend from this pedigree, however, three of them (4.05%) were also from the Afric-"Sor" family, but we could not find a connection with that pedigree due to inadeguate marital data before 1760. In the Veli Brgud village, there also were 4 (5.41%) patients of non-Afric families with no other affected members. From the total of 330 marriages, 73 (22%) were consanguineous. According to our results, the mode of inheritance of glaucoma simplex in the Afric-"Sor" pedigree was of a dominant pattern. PMID- 9988905 TI - How prepared are you? PMID- 9988906 TI - A brief child mental health assessment for general practitioners. PMID- 9988907 TI - Abdominal pain and drug addiction. PMID- 9988908 TI - Should GPs be managing musculoskeletal problems? PMID- 9988909 TI - Six week postnatal check up. PMID- 9988910 TI - Cancer and chronic pain. AB - BACKGROUND: The effective management of cancer pain is one of the greatest challenges for GPs. OBJECTIVE: Pain management can be best achieved with a knowledge of the fundamentals of cancer pain and its assessment. A systematic and holistic approach to its treatment needs to be individualised for each patient, taking into account the relevant physical, psychological and spiritual factors. DISCUSSION: GPs are part of a team including oncologists, palliative care specialists, nursing services, paramedical staff, counsellors and clergy and so should know about and make use of the ever-improving support services which are available to ensure that insoluble pain problems are a rare occurrence. PMID- 9988911 TI - Chronic low back pain. What are the treatment options? AB - BACKGROUND: Chronic low back pain is a relatively common occurrence in general practice and there is much that the family doctor can do to help. OBJECTIVE: An important aspect of the management is to be able to identify red and yellow flag conditions which, if undiagnosed, can become a serious health risk. DISCUSSION: Being aware of the possibility that red and yellow flag conditions exist alerts the practitioners to which questions to ask and what the management might be. Patients suffering benign low back pain can be helped to cope by the use of several easily implemented modalities. PMID- 9988912 TI - Common pain scenarios. AB - BACKGROUND: Vertebral fractures and fibromyalgia, while very different and unrelated clinical conditions, are common pain conditions that can, at times, be difficult to diagnose and manage. OBJECTIVE: To discuss the investigation and treatment of two common pain conditions. DISCUSSION: Following a structured program for assessment and treatment, most people with both of these conditions can experience substantial improvement in the quality of their life. PMID- 9988913 TI - Chronic pain and depression. AB - BACKGROUND: People presenting with chronic non-malignant pain provide the health practitioner with a therapeutic challenge. As medicine moves towards an emphasis on evidence based treatments, practitioners are reassessing approaches to chronic non-malignant pain. Depression is a common comorbidity that compounds the challenge, often going unrecognised. OBJECTIVE: To provide the reader with an insight into the current understanding of the comorbidity of chronic pain and depression, and an appreciation of the impact the two syndromes have upon each other. To assist the reader in understanding the biopsychosocial perspective, and to provide an introduction to various treatment approaches. DISCUSSION: It is a reality that general practitioners will carry the responsibility for the management of chronic pain sufferers as the multidisciplinary clinics continue to struggle with their unmanageable waiting lists. This article discusses the conceptual shift from the traditional medical model regarding the management of pain and pain related disorders. PMID- 9988914 TI - Control and cardiovascular risk factors of hypertension. An assessment of a sample of patients. AB - OBJECTIVES: To monitor the documentation of blood pressure measurements and other cardiovascular risk factors in general practice patients with hypertension. METHOD: Twenty-five case notes of patients diagnosed as hypertensive were randomly selected from each of 58 participating general practitioners in suburban general practice in Adelaide, South Australia and were monitored by two registered nurses. MAIN OUTCOME MEASURES: to assess whether blood pressure readings, weight, smoking history, alcohol intake and family history were documented, and whether electrocardiogram, plasma lipids, urinalysis and biochemical screen (which includes blood urea nitrogen, creatinine, glucose, electrolytes and uric acid) had been undertaken. RESULTS: Data from 1446 hypertensive patients showed that for the last three blood pressure values recorded, 483 (33%) had an average level of 140/90 mm Hg or less and 1100 (76%) had an average of 160/95 mm Hg or less. The other cardiovascular risk factors selected were variably recorded, with biochemical screen being most commonly recorded [1198 (83%)] and family history [423 (29%)] the least. CONCLUSIONS: Inadequacies in the control of hypertension and in the documentation of other cardiovascular risk factors suggest that further educational initiatives are required in this common chronic illness. PMID- 9988915 TI - Dementia in Down syndrome. Untangling the threads. AB - Despite frequent neuropathological findings, the prevalence of dementia in people with Down syndrome is thought to be no higher than in the general population. The age of onset, however, is approximately two decades earlier. The most important factor in the general practitioner's assessment of a person with this syndrome who appears to be dementing is the exclusion of medical problems that may be masquerading as Alzheimer disease. This article presents an efficient system for the clinical review of people with Down syndrome who are declining in function. The system is also adaptable for use with people who do not have this syndrome. PMID- 9988916 TI - Measuring immunisation coverage in Australia. A review of the Australian Childhood Immunisation Register. AB - BACKGROUND: Before the establishment of the Australian Childhood Immunisation Register (ACIR), measurement of childhood immunisation coverage in Australia involved a variety of methods at varying intervals by general practice (GP) divisions, state health departments and the Australian Bureau of Statistics. Such surveys may underestimate (child health records) or overestimate (parental recall) true immunisation coverage. OBJECTIVE: The establishment of the ACIR in 1996 (a world first), was a huge undertaking involving 15,000 immunisation providers (60% GPs) notifying over 3 million immunisations annually. This review summarises the operation of the ACIR, how it calculates coverage, the accuracy of estimates from the ACIR and how Australia's immunisation coverage compares with that of other similar countries. Currently, the accuracy of the records on the register is questioned, especially in urban areas, but available data suggest that failure to report to the ACIR is the main source of data discrepancies. DISCUSSION: The ACIR has the potential to measure immunisation coverage at any practice or local level with accuracy and timeliness. With full provider participation, the ACIR is capable of identifying areas of low immunisation coverage for targeted interventions and will play a key role in the current measles campaign, the General Practice Immunisation Incentives scheme and in payments to parents. Achieving the highest possible completeness and timeliness of the ACIR is in the interests of providers, consumers and health planners. PMID- 9988917 TI - Sigmoidoscopy. Is it a general practice procedure? AB - Sigmoidoscopy can readily be learnt and practised by a general practitioner interested in looking after patients with colorectal problems. Examination with a rigid sigmoidoscope has advantages over use of the flexible instrument for the frequent user. Details of the equipment needed for sigmoidoscopy as well as a method, precautions and some typical findings are described. PMID- 9988918 TI - Putting prevention into practice: just do it. PMID- 9988919 TI - Confidence and competence in dealing with emergencies. PMID- 9988920 TI - General practitioner preparedness to respond to a medical disaster. Part I: Skills and equipment. AB - OBJECTIVE: Financial constraints are leading to the downgrading or closure of many country hospitals throughout Australia. There is concern that general practitioners (GPs) could become deskilled if they lose access to a local hospital. A recent survey of Victorian rural GPs showed that rural GPs in towns without hospitals had different characteristics and working conditions from those with hospital access and backup. Campbell uncovered an apparent paradox: GPs without hospitals were more likely to have emergencies brought directly to their surgeries, and had more equipment in their surgeries, yet they had significantly lower confidence in emergency skills. METHOD: A questionnaire was sent to 100 general practitioners in two rural divisions of general practice in Victoria, Australia. They were asked to indicate their confidence in performing 18 emergency procedures. They were also asked whether they had available the necessary equipment. RESULTS: We have assessed the availability of GP emergency skills and equipment in two rural divisions of general practice--one with, the other without, local hospitals. The division without hospitals scored significantly lower in skill levels. A close correlation was found between skill levels and equipment availability. There has been a significant reduction in skill levels in both divisions over time. CONCLUSION: The skills necessary for the stabilisation of a single patient with a life threatening condition are not dissimilar from those needed to treat such a patient in a multiple victim scenario, although the approach and external pressures may be different. These skills, then, are essential to all general practice. The information sought in this survey would be important in the assessment of GP preparedness for both single-victim and multiple-victim (disaster) emergencies. The results of this study raise doubts as to the ability of at least one division to respond to a disaster. PMID- 9988921 TI - General practitioner preparedness to respond to a medical disaster. Part II: Ability and training. AB - OBJECTIVE: Part I of this paper looked at the availability of 18 individual skills in two rural Victorian divisions of general practice, one with hospitals, and the other without. It looked at the deskilling of rural general practitioners and highlights a direct relationship between skill and equipment availability, and in particular, the effect of a local hospital. METHOD: By analysing the data in Part I, this paper looks at the availability of rural GPs with the ability to perform a range of 15 pre-hospital skills and analyses the effect of retraining in selected skills. RESULTS: Part I identified needle and surgical cricothyrotomy as weaknesses requiring retraining in both divisions. Refreshing these led to a modest improvement only. In addition to the cricothyrotomies, retraining in one skill (as chosen by the GP), will increase to over 50% in both divisions, the percentage of GPs with the first nine skills only. CONCLUSIONS: We found that neither division currently has adequate numbers of GPs with the required range of skills to allow for a GP based response to a disaster. Retraining the GP in both the cricothyrotomies and two self-nominated weakest skills resulted in adequate numbers of skilled GPs. The former can be provided by mass training and the latter requires a more personalized training. A 'travelling circus' format is described as a suitable means for this retraining. It also improves networking among health professionals likely to be involved in a disaster, and offers infrastructure support for GP involvement in emergency management, a public education vehicle, and a research vehicle for the study of critical and emergency care to rural areas. PMID- 9988922 TI - Gastroesophageal reflux and quality of life. Patient's knowledge, attitudes and perceptions. AB - INTRODUCTION: Gastroesophageal reflux (GER) is one of the most common conditions seen in general practice. The objective of this study was to determine patients' knowledge and attitudes about GER and its effects on their stated quality of life. METHODS: A cross sectional survey using a self administered questionnaire of a random sample of 400 patients, from the principal author's practice in outer western Sydney. RESULTS: GER affected 53% of this sample of patients with Asians and manual workers being overrepresented. In 62% of these, GER was shown to adversely affect quality of life. Most patients in this study (70%) were unaware of the potentially serious complications of GER. CONCLUSION: The prevalence of GER and the impact of the condition on sufferers' quality of life is generally unknown but requires further research. A history of cough and hoarse voice with no known cause, should be investigated for GER. Most patients are unaware of the serious complications of GER and should be educated about these. PMID- 9988923 TI - Information technology and general practice. A survey of general practitioner attitudes towards computerisation. AB - AIM: General practitioners in the central Sydney area were surveyed to quantify the extent of, and attitudes towards, computerisation in Australian general practice. METHOD: Two surveys were mailed to all GPs in the central Sydney area, first in 1994, and again in 1996. The majority of questions in both surveys were identical. The results were collated and descriptive and comparative statistics calculated. RESULTS: There was an increase in the use of computers for clinical tasks and, GPs' attitudes towards computerised prescribing systems became more positive. There was a persistent negative attitude towards the actual costs of computerisation. CONCLUSION: Methods are now required to transform the increased use of computers by GPs into improved outcomes for them and their patients. PMID- 9988925 TI - Skin cancer in general practice in South Australia. A five year study. AB - OBJECTIVE: Most data on the prevalence and behaviour of skin cancers is based on hospital studies. The scarcity of community based general practice skin surveys prompted this study. The aim of the survey was to: record the relative frequency of different skin tumours in an Adelaide general practice and compare these with rates published elsewhere. to record clinical accuracy of diagnosis, infection rates and completeness of excision. METHOD: Five year prospective study recording age, sex, site of excision and histological diagnosis of 369 skin excisions in a general practice. A substudy recorded clinical diagnostic accuracy, with subsequent histological diagnosis. RESULTS: Non-melanotic skin cancer (NMSC) accounted for 59.9% of the total lesions with basal cell carcinomas (BCCs) accounting for 30.6%, squamous cell carcinomas (SCCs) 21.7%, and intra epithelial cancer 7.6%. The most frequent excision site was head, neck and face. A total of 75% of SCCs occurred on sun exposed areas, whereas a significant proportion of BCCs occurred on the shoulder and trunk (37.1%); this agrees with recent trends in Australia. Clinical accuracy when compared with histology was 77% comparing favourably with other published data. CONCLUSION: Skin cancer continues to be a major community health issue in Australia in which general practitioners are heavily involved. Due to their expertise and early intervention at a community level, much is being done to reduce this cost in the community. Further research on NMSC trends are needed, especially in general practice. PMID- 9988924 TI - Parent and general practitioner preferences for infant immunisation. Reactogenicity or multiple injections? AB - AIM: To explore the relative importance parents and general practitioners place on less reactogenic vaccines and multiple injections at each childhood immunisation encounter. METHOD: A random sample of western Sydney parents (n = 162) and GPs (n = 154) completed telephone questionnaires about their preference for either a single injection of pentavalent vaccine (whole-cell pertussis/diphtheria/tetanus/Hib/hepatitis B), or regimen containing the less reactogenic acellular pertussis vaccine requiring two separate injections (acellular pertussis/diphtheria/tetanus and Hib or three separate injections (acellular pertussis/diphtheria/tetanus and Hib and hepatitis B). Potential confounders were examined by univariate and multivariate analysis. RESULTS: Regimens containing acellular pertussis vaccine (2 injections or 3 injections) were preferred by 72% and 58% of parents respectively. Those whose children were already vaccinated were less concerned about side effects and were twice (or = 2.0, 95% CI 1.0-4.0) as likely to select the pentavalent (single injection) option. 69% and 77% of GPs preferred the pentavalent rather than the two or three injection acellular option, although previous experience with a systemic adverse reaction to immunisation increased their preference for the acellular pertussis vaccine (or = 2.9, 95% CI 1.1-7.6). Only 54% of parents and 28% of GPs favoured three injections at one visit. CONCLUSION: Parent and GP concerns regarding reactogenicity and multiple injections differ. Parents are more concerned about vaccine reactogenicity than multiple injections. However, if the GP recommends a particular regimen, it is likely to be accepted by parents. PMID- 9988926 TI - Estimating and generalizing with clustered sampling in general practice. AB - General practice research focusing on patients may involve risk factors, morbidity, medication use or patient satisfaction. When collecting information about patients it is often easier, cheaper and more appropriate to enlist the support of a number of general practitioners (GPs) who provide access to a number of patients. Such studies utilise a 'cluster sampling' (CS) design, as clusters or groups of patients around a GP are used for the investigation. In analysing data from these studies it is necessary to consider the impact that the study design will have on the variance structure of data collected. PMID- 9988927 TI - The concept mapping method. An alternative to focus group inquiry in general practice. AB - BACKGROUND: The concept mapping rationale and process are explained step by step. The concept mapping method produces a two dimensional conceptual map of ideas produced by the group which can be analysed at the level of individual statements, clusters of statements, and groups of similar clusters. An example of concept mapping conducted with four general practitioner (GP) groups from different practice types and demographic locations is provided. A total of 51 participating GPs were asked to complete an 'evaluation questionnaire' at the end of each group session. The majority of GP participants (68%) rated the method as highly useful. OBJECTIVE: To describe the concept mapping method and its interpretation for use in general practice research. To report on its perceived usefulness and acceptability by general practitioners. DISCUSSION: Concept mapping is a very useful method combining benefits from qualitative and quantitative approaches for exploring the breadth of a topic in its entirety, especially for abstract concepts. GPs found the concept mapping method to be efficient for group inquiry, rating it high on utility. There is scope to refine the method, reducing time spent in some stages of the session, and substituting more time on final analysis. PMID- 9988929 TI - The hard choice facing Australian general practice. Is it time to join the health system? PMID- 9988928 TI - Improving preventive practice. An educational intervention using chart audit. AB - OBJECTIVE: To assess if the impact of teaching preventive medicine can be increased by supplementing conventional teaching with a practice based preventive audit undertaken by general practice registrars and their supervisors. METHOD: A practice based medical record audit of preventive activities was undertaken by 30 general practice registrars and 27 of their supervisors. Items recorded were based on the RACGP's Guidelines for Preventive Activities in General Practice. Participants were also asked to identify or target areas identified by the audit which they specifically wished to improve. Following an educational program on preventive medicine for both groups, the audit was repeated to assess changes made. RESULTS: Both registrars and supervisors increased their level of prevention in most parameters measured. Registrars' scores were lower than supervisors' for all items in the initial audit but they made greater improvements by the repeat audit (p < 0.02 for all items). There was great variability between the level of recording of preventive data--from rubella immunity (which was recorded in only 22% of cases) to blood pressure (which was recorded in 94% of cases). There was also variability between practices. Items specifically targeted for improvement by participants did not improve more than other items. CONCLUSION: Supplementing conventional teaching with a practice based audit improved the level of preventive medicine undertaken in teaching practices, by both registrars and supervisors. PMID- 9988930 TI - Is the dose in the therapeutic range? PMID- 9988931 TI - Is it truly random? PMID- 9988932 TI - A new treatment for high grade gliomas of the brain. AB - The data confirmed the fact that repeated administrations of iodine-125 labeled anti-epidermal growth factor receptor 425 is safe and may have benefited the management of primary high grade gliomas of the brain as well as recurrent astrocytomas. At present, a randomized control phase III trial is in the process of being initiated to evaluate the benefits that would accrue in a controlled environment. PMID- 9988933 TI - Molecular aspects of preterm labor. AB - Preterm birth is a major problem in clinical obstetrics, occurring in approximately 10% of all pregnancies, and leading to 75% of early neonatal mortality and morbidity. Studies in our laboratory have examined the neuroendocrine mechanisms by which the fetus, through activation of the hypothalamic-pituitary adrenal axis, provides the stimulus to the onset of parturition. Maturation of this axis occurs prematurely in response to stimuli such as stress. Stress induced activation of HPA function in human pregnancy, may lead to increased output of corticotropin-releasing hormone (CRH) from placenta and fetal membranes. CRH is one of the agonists that acts in concert with increased prostaglandin biosynthesis to provide the stimulus to myometrial contractility in late gestation. Recent studies have also recognized that approximately 15% of patients in idiopathic preterm labor present, with deficiency of the major prostaglandin metabolizing enzyme in the fetal membranes, particularly chorionic trophoblast. Understanding these processes may lead to new methods of managing the patient presenting in preterm labor. PMID- 9988934 TI - ["Taxanes: an action mechanism at the cellular level, significant clinical progress in the treatment of cancers of the ovary and breast"]. AB - The past decade has witnessed the development of a new class of cytotoxic agents with a new mechanism of action: the Taxanes. These compounds promote tubulin assembly in microtubules and inhibit their depolymerisation; as a result, they compromise a number of vital cellular functions in which microtubules play a critical role; of note, is the fact that they seem to be relatively "p53 independent", contrary to many cytotoxic agents in current clinical use. Taxol represents a "breakthrough" in the treatment of ovarian cancer, and Taxotere is a major step forward in the treatment of breast cancer. The Jules Bordet Institute has actively contributed to the clinical development of these two compounds in these two indications. PMID- 9988936 TI - Diastolic function and dysfunction with exercise, hypertrophy, ischemia, and heart failure. PMID- 9988935 TI - [Augmentation of transdermal drug penetration]. AB - Transdermal drug delivery is an alternative to conventional routes of administration. It is limited due to the low permeability of the skin. Iontophoresis (application of low intensity current) and electroporation (application of high voltage pulses) increase drug delivery by several orders of magnitude. The mechanisms and the parameters controlling drug transport as well as safety issues have been studied. New therapeutic applications for the delivery of drugs, peptides and nucleic acids, have been developed. PMID- 9988937 TI - [Coronary artery anomalies in the young]. PMID- 9988939 TI - Regulation of lung water. PMID- 9988938 TI - [Arrhythmogenic right ventricular cardiomyopathy]. PMID- 9988940 TI - [Patients at risk or patients at no risk after uncomplicated myocardial infarction? The COSTAMI project]. PMID- 9988941 TI - [Dual-chamber DDD pacing in NYHA III-IV functional class dilated cardiomyopathy: short and middle-term evaluation]. AB - Effectiveness of dual-chamber pacing in patients with dilated cardiomyopathy is still controversial. Our study was performed: to select the most favorable individual atrioventricular (AV) delay; to compare hemodynamic short-term effects in each patient after 2 periods of DDD pacing and sinus rhythm (AV spontaneous); to assess hemodynamic long-term (1 year) effects after DDD pacing at optimum AV delay. In 1996, 9 patients (7 men, 2 women; mean age 69 +/- 5 years) with dilated cardiomyopathy (5 idiopathic, 4 ischemic), NYHA functional class III-IV, ejection fraction < 30%, end-diastolic volume > 60 ml/m2, mitral regurgitation +2/+3, PR interval > or = 200 ms, were enrolled. All patients were implanted with DDD pacemakers and monitored for: ejection fraction and end-diastolic volume (measured by echocardiography and radionuclide angiography); clinical conditions; exercise tolerance and maximum oxygen consumption (by Weber exercise protocol); neurohormonal activity (plasma renin, aldosterone, atrial natriuretic factor). Data were recorded: before DDD implantation; after 2 randomized, single-blind periods of 3 months in VVI mode (at ventricular "sentinel" rate of 50 b/min) and in DDD mode with the optimum AV delay, corresponding for each patient to the minimum end-diastolic volume measured by radionuclide angiography and to the highest cardiac output recorded by echocardiography; after 6 months of DDD pacing with most favorable AV delay. Three more patients died 6 months after (between sixth and twelfth month of follow-up), due to refractory heart failure; 1 patient dropped out because his pacemaker was programmed in VVI mode at low rate, due to intolerance of DDD pacing. Among the other 4 patients no clinical and laboratory parameters were significantly different after 1 year of follow-up. In conclusion, DDD pacing in selected patients with dilated cardiomyopathy showed disappointing results, despite a strict and laboratory monitoring; DDD pacing could be of major benefit in larger populations, according to Doppler mitral flow pattern: those patients with a larger A-wave amplitude could be more sensitive to DDD pacing than those with evidence of poor atrial systole. Moreover, biatral and/or biventricular pacing could also play a significant role. PMID- 9988942 TI - [Incremental doses of diltiazem in patients with coronary artery disease in end stage renal failure maintained on hemodialysis: which is the optimal dose?]. AB - End-stage renal disease patients on maintenance hemodialysis suffering from coronary artery disease probably receive too low doses of calcium-antagonists, because the attempt to avoid adverse effects prevails the well-documented antianginal activity of the drug. The aim of our study was to assess the safety and efficacy of incremental doses of diltiazem in treating angina pectoris in hemodialyzed patients with coronary artery disease, to identify the optimal dose. Ninety-four chronic hemodialyzed patients (59 males and 35 females; mean age 55.2 +/- 3.3 years; on periodic dialysis for 80.3 +/- 25.6 months) with coronary artery disease and more than 5 min of transient myocardial ischemia during 48 hours of Holter monitoring were included in the study. A double-blind, randomized, placebo-controlled trial design was used. Incremental doses of diltiazem (from 120 to 240 mg/day) were administered in 4 months. At doses of 120 and 180 mg/day it was observed a statistically significant reduction in the number and duration of total and symptomatic ischemic episodes in 48 hours, compared with baseline (p < 0.001). Instead, the number and the duration of silent ischemic episodes did not significantly change (NS). The efficacy on silent myocardial ischemia was obtained only with the dosage of 240 mg/day (p < 0.001). If this dosage was obtained with a sustained-release formulation (120 mg twice a day), the efficacy was similar to the administration of 4 tablets/day of 60 mg, but the tolerability was better, especially during dialysis. The circadian variations of transient ischemic episodes showed two peaks in the 24 hours, one from 6.00 to 9.00 a.m. and another from 4.00 to 8.00 p.m., just during the dialysis. Both peaks were reduced only with 240 mg/day. In conclusion, this study demonstrates that sustained-release diltiazem (120 mg twice a day) is greatly useful in patients with coronary artery disease on maintenance dialysis because it reduces the frequency of silent ischemic episodes, has a good tolerability, and modifies the circadian pattern of ischemic episodes, reducing both peaks during the day. PMID- 9988943 TI - Effect of creatine phosphate on the contractile activity in acutely failing rat heart. AB - The hypothesis was tested that infusion of a solution containing creatine phosphate (CP) into rats with acutely failing hearts would enhance recovery of cardiac function. The acutely failing heart was produced by constricting the ascending aorta. This overload produced failure in approximately 25 min. At the point of failure the constriction was removed and solutions containing sterile physiological saline (PSS), PSS and CP, PSS and creatine, or PSS and creatine plus phosphate were infused. Cardiac function was assessed from systolic and diastolic blood pressure, +/- dp/dt, heart rate, and cardiac work. Ca2+ uptake by isolated sarcoplasmic reticulum and the concentrations of selected blood and tissue metabolites were measured. Normal cardiac function was restored in the PSS CP infused rats whereas all other treatments did not restore cardiac function. Adenosine triphosphate and CP had declined in the myocardium of the failing hearts while lactate was elevated. The concentrations of these metabolites were normal in the PSS-CP infused animals. The glycogen concentration in the myocardium was reduced following the constriction. Ca2+ uptake by isolated sarcoplasmic reticulum was depressed in the failed hearts but normal in the hearts of CP-infused animals. These results demonstrate that the infusion of CP into animals with failing hearts can be effective in restoring cardiac function. PMID- 9988944 TI - Brief periods of occlusion and reperfusion increase skeletal muscle force output in humans. AB - Prolonged periods of ischemia/reperfusion are known to deleteriously affect skeletal muscle performance. However, in animal models, brief bouts of both skeletal and cardiac muscle ischemia/reperfusion have been shown to decrease skeletal muscle injury and increase skeletal muscle force output, a phenomenon termed "preconditioning". Because there are transient periods of ischemia/reperfusion during isometric and concentric muscle contractions, the purpose of this study was to examine how short duration forearm occlusion/reperfusion prior to exercise, influenced isometric skeletal muscle force output in humans. Eleven subjects (6 men and 5 women, mean age 25 +/- 1 years) participated in this study. Using a Biodex multijoint ergometer, a protocol of isolated, isometric forearm wrist flexions was utilized to measure muscle force output in two separate trials. In the first trial, 15 isometric maximal voluntary contractions (MVCs) of the wrist flexors were performed in 20 intervals interspersed with 10 s of rest. In the second trial, forearm occlusion was induced (2 min at 200 mmHg by blood pressure cuff occlusion, with 10 s of hyperemia) prior to exercise. Following cuff occlusion, an identical exercise protocol was followed, i.e. 15 isometric wrist flexor MVCs performed in 20 intervals interspersed with 10 s of rest. The total force output over 15 MVCs was greater following intermittent cuff occlusion (no occlusion 2619 +/- 320 ft.lbs vs cuff occlusion 2986 +/- 195 ft.lbs; p < 0.05). The mean force output per MVC also increased during exercise following intermittent cuff occlusion (no occlusion 174 +/- 21 ft.lbs vs cuff occlusion 199 +/- 13 ft.lbs; p < 0.05). In a second set of experiments, we found a 3 to 4 fold hyperemic blood flow following cuff occlusion. These data suggest that brief periods of cuff occlusion/reperfusion may increase repetitive MVC force output by skeletal muscle. Although further study is needed to fully understand the effects of occlusion/reperfusion on skeletal muscle force output, we hypothesize that, in part, this putative effects is secondary to the hyperemic blood flow which follows cuff occlusion. PMID- 9988945 TI - [Role of hypertension in determining valvular diseases in patients with chronic uremia and dialytic treatment]. AB - Patients in chronic dialysis have a higher prevalence of cardiovascular morbidity and mortality, together with higher prevalence of hypertension and valvular diseases. It is not clear whether aortic and mitral defects are linked to the effect of chronic dialysis (for instance hypercalcaemia or hyperparathyroidism) or to hypertension. In order to see whether these factors could independently affect the single valve diseases we studied 48 patients in chronic dialysis. Patients were divided into hypertensive and normotensive. A population of hypertensive and another of normotensive, non-dialyzed patients served as control. The presence of valvular disease was searched by mean of echocardiography. We also investigated the length of dialytic treatment and the levels of parathyroid hormone in order to see if any correlation with the single valve defects existed. Aortic stenosis and insufficiency were not related to hypertension suggesting that circulating factors are likely to be involved in the pathogenesis of this valvulopathy (chi 2 = 6, p < 0.01 between hypertensive and normotensive in dialysis; chi 2 = 6.1, p < 0.01 between patients in dialysis and normotensive non uremic, for aortic stenosis; chi 2 = 12.1, p = 0.02 between non uremic normotensive and dialyzed, for aortic insufficiency). On the contrary for mitral regurgitation we did not find differences between dialyzed patients and controls (chi 2 = 18.2, p < 0.0001 between uremic hypertensive and controls). There was a significant difference in both groups between hypertensive and normotensive subjects suggesting that hypertension plays an important role in this valvulopathy. Mitral and aortic calcifications were more frequent in the uremic patients (55% in hypertensive uremics, 33% in normotensive uremics, 16 and 25% in non uremics). PMID- 9988946 TI - [Cardiovascular abnormalities in Kawasaki disease. An Italian prospective study]. AB - We report a prospective study performed over a 9 year period in 96 children with Kawasaki disease (mean age 35 +/- 29 months), 84 of whom < 5 years of age. The male/female ratio was 1.5 (57/39). A total of 38 patients had cardiac involvement, including flattened T waves in the ECG (10 patients), pericardial effusion (6 patients), myocarditis (1 patient), and coronary artery aneurysms (25 patients; frequency of aneurysms: 26%). All patients were evaluated during the acute phase (first month) of the illness. The first echocardiographic examination was performed 15 days (range 4.30 days) from the appearance of fever, and coronary aneurysms were observed in 23 patients; in 2 patients, however, aneurysms appeared later (2 and 6 months). Aneurysms were small (< or = 4.5 mm) in 12, medium (4.5-7 mm) in 11, and large (> 7 mm) in 12 patients. Male sex (p = 0.02), age < 12 months (p = 0.005), ESR (p = 0.001), platelet count (p = 0.009), and pericardial effusion (p = 0.02) were significantly related to the presence of aneurysm. Among females, incidence of aneurysms was significantly higher in infants < 12 months than in older patients (60 vs 6%, p < 0.001). Intravenous immunoglobulin treatment was started early (within 10 days) in 61 patients and late (> 10 days) in 22. Compared to late treatment, early i.v. immunoglobulin treatment was associated with smaller aneurysms and higher regression rate (67 vs 28%, p < 0.05). No difference was observed concerning frequency and number of dilated vessels as related to therapeutical regimens. Total i.v. immunoglobulin dose (2 g/kg) was administered over 1-2 days in 26 patients (scheme I) or over 4 5 days in 58 (scheme II). Frequency of aneurysms was significantly lower in patients treated early (p = 0.02). No myocardial infarctions or deaths occurred at short- or long-term follow-up. PMID- 9988947 TI - [Hypertrophic cardiomyopathy during adrenocorticotrophic hormone administration in infants: a case report]. AB - We report a 2-month-old child with infantile myoclonic seizures, who developed congestive heart failure secondary to hypertrophic cardiomyopathy while receiving adrenocorticotropic hormone (ACTH) therapy. Treatment with propranolol and withdrawal of ACTH led to the resolution of cardiac hypertrophy as determined by two-dimensional echocardiography. Possible links between ACTH therapy and the development of hypertrophic cardiomyopathy are examined. Our report confirms that a careful monitoring is required to detect cardiac abnormalities during ACTH administration. PMID- 9988948 TI - [Effects of enalaprilat on postischemic microvascular hyperpermeability in isolated working rat hearts]. PMID- 9988949 TI - [Three hundred years of history: from the first blood transfusion (1667) to the first heart transplantation (1967)]. PMID- 9988951 TI - Is stress linked to heart disease? The evidence grows stronger. AB - Acute stress caused by strong emotions such as fear can sometimes cause sudden death in people with underlying coronary artery disease (CAD). Chronic mental stress may also promote the long-term development of coronary disease, although the distinction between Type A and Type B personalities appears overly simplistic. Stress-management interventions measurably improve CAD patients' performance on cardiac function tests, and should be incorporated more often in standard cardiac rehabilitation programs. PMID- 9988952 TI - New technology and new challenges for assisted reproduction. AB - As assisted reproduction technology advances, more types of procedures are becoming available, bringing more success at solving many types of infertility. In vitro fertilization has become simpler and less invasive, with success rates as high as 30% per cycle. Intracytoplasmic sperm injection has solved many types of male infertility. This article explains in vitro fertilization technology and discusses such ethical issues as embryo ownership, multiple births, and embryo genetic testing. PMID- 9988953 TI - A 55-year-old man with idiopathic recurrent pancreatitis. PMID- 9988954 TI - Evaluating back pain in older patients. AB - Low back pain in the elderly has a much wider range of possible causes than in younger patients. In addition to nonspecific mechanical causes, malignancy presenting as back pain occurs more often in older patients. Other systemic and visceral causes of back pain such as polymyalgia rheumatica, aortic aneurysm, Paget disease, Parkinson disease, and osteoporosis with compression fracture occur almost exclusively in persons over age 50. Keys to diagnosis and management of low back pain in older patients are presented. PMID- 9988955 TI - Invasive vs conservative management of non-Q-wave myocardial infarction. AB - In the Veterans Affairs Non-Q-Wave Infarction Strategies in Hospital (VANQWISH) trial, most patients with non-Q-wave myocardial infarction (MI) fared no better with early invasive management (i.e., diagnostic angiography within 2 to 3 days, followed by revascularization if indicated) than with a more conservative approach (i.e., radionuclide ventriculography and thallium stress testing as initial diagnostic tests). These results should not be construed to diminish the value of early diagnostic angiography, which in patients with non-Q-wave MI provides essential information for determining the need, timing, and method of revascularization. Until more information is available that incorporates contemporary practices and outcomes in patients with non-Q-wave MI, early coronary angiography should remain an acceptable method of risk stratification and should be followed by appropriate medical therapy or revascularization. PMID- 9988956 TI - Aggressive blood pressure lowering is safe, but benefit is still hard to prove. AB - In the Hypertension Optimal Treatment (HOT) study, hypertensive patients who were randomly assigned to undergo antihypertensive treatment to achieve a goal diastolic blood pressure of 80 mm Hg or lower did not experience fewer cardiovascular events than did patients who received treatment with goal pressures of 85 or 90 mm Hg. Such aggressive antihypertensive treatment was safe and well tolerated, and did result in fewer cardiovascular events in the subset of patients with diabetes. All patients were randomly assigned to take aspirin 75 mg/day or placebo, and patients in the aspirin group had a 15% lower rate of major cardiovascular events and myocardial infarctions than did patients who received placebo. This finding establishes the efficacy of aspirin in preventing strokes and myocardial infarctions in hypertensive patients. PMID- 9988957 TI - Issues and controversies in venous thromboembolism. AB - This paper gives specific recommendations on a number of issues in venous thromboembolism: how to evaluate idiopathic deep vein thrombosis (DVT); how to treat calf vein thrombosis and upper-extremity DVT; how to use low-molecular weight heparin, vena cava filters, catheter-directed thrombolytic therapy, and compression stockings; how long to continue anticoagulation therapy; and how to manage recurrent DVT. PMID- 9988958 TI - Prostate cancer screening. PMID- 9988959 TI - Infectious diseases in England and Wales: April to June 1998. PMID- 9988960 TI - Seasonal rise in meningococcal disease: chief medical officer writes to all doctors. PMID- 9988961 TI - The rise and fall of salmonella? PMID- 9988962 TI - A possible digital domain for nursing. PMID- 9988963 TI - Development of a computerized database for evaluation of nurse practitioner student clinical experiences in primary health care. Report of three pilot studies. AB - A computerized database for the collection of patient encounter information by nurse practitioner students provides insight into the number and diversity of cases seen. Menu-driven data entry and controlled vocabulary in the form of diagnostic clusters provide a mechanism to categorize and analyze the data. Faculty are able to review student clinical experience by quantitative measures such as number of patient encounters, diagnostic cluster of the encounter, and patient demographic data. Qualitative measures such as student's level of responsibility and student prior experience with stated encounter also are included in the database. Data analysis of two interdisciplinary pilots provided comparisons across disciplines of nursing, medicine, and physical therapy. A subsequent nurse practitioner student pilot provided further refinement and a broadened database terminology more inclusive of a nursing perspective. Educational and clinical issues involved in development, maintenance, and future use of the database are discussed. PMID- 9988964 TI - Wired for thought. Electronic meetings in nursing education. AB - Expanded application of electronic meeting software (EMS) in the business world is attributable to its discovery as a time saving and cost effective strategy for team building and group process. Group process and team building are equally important functions within the higher education environment but frequently consume hours of attention with limited productivity. Enhancements in EMS programs promise exciting solutions for completing crucial activities including strategic planning, negotiating, problem solving, consensus building, faculty/staff evaluation, multidisciplinary research and classroom instruction. The College of Nursing and Health at Wright State University in Dayton, Ohio has been "wired for thought." This article presents applications of GroupSystems electronic meeting software from Ventana Corporation, Tucson, Arizona, for solving problems encountered in administration, research collaboration, and classroom teaching within the College. PMID- 9988965 TI - Intensive care unit bedside documentation systems. Realizing cost savings and quality improvements. AB - Automating intensive care unit (ICU) documentation saves time and assists in interpreting data and planning care. The current economic climate makes the cost of ICU computer systems prohibitive for many institutions. Any expenditure without a measurable return on investment will be scrutinized carefully. The literature describing ICU computer system benefits often is difficult to interpret. No two implementations, hospitals, or benefit study designs have been the same. Each implementation has many unique variables. These variables make study comparison and replication potentially impossible. The authors have concluded that replicating previous studies may not be relevant if the goal is to justify system cost. The objective is met by designing a study that evaluates changes in data management activities as well as issues unique to the study unit or institution. The purpose of this article is to review the findings of previous benefits studies related to ICU documentation systems and to suggest other measures to support cost justification for expensive bedside documentation systems. PMID- 9988966 TI - Faculty experiences with providing online courses. Thorns among the roses. AB - This article presents a review of the literature summarizing faculty reports of their experiences with computer-mediated distance education compared with their traditional face-to-face teaching experiences. Both challenges and benefits of distance learning programs contrasted with classroom-based teaching are revealed. Specific difficulties and advantages identified by online faculty were categorized into four broad areas of impact on the teaching/learning experience: (a) faculty workload, (b) access to education, (c) adapting to technology, and (d) instructional quality. Challenges appear to be related predominantly to faculty workloads, new technologies, and online course management. Benefits identified by online educators indicate that computer-mediated distance education has high potential for expanding student access to educational resources, for providing individualized instruction, and for promoting active learning among geographically separated members of learning groups. PMID- 9988967 TI - Fever of unknown origin--past present and the future. PMID- 9988968 TI - Knowledge and self-care practices of diabetics in a resettlement colony of Chandigarh. AB - Self-care is an important component of diabetes control programme. A cross sectional survey was carried out in a resettlement colony of Chandigarh and 60 diabetics aged 20 years and above were identified. Their knowledge and practices regarding diet, genital hygiene, care of foot, wound, complications of diabetes and medication was assessed using a semistructured interview schedule. Most of them (60%) opined that diabetic should consume whatever is cooked in the family. Forty eight diabetics knew that sweets and fatty foods should be avoided but only 18.3% were avoiding them. Genital hygiene was maintained by 51.7% and foot care was done by 63.3% through regular washing. Monitoring of blood sugar was poor (46.7%), only 3 knew and were continuing self testing of urine. Oral anti diabetic drug compliance rate was 62.9%. None of the patients on insulin injections knew about self therapy. Knowledge regarding diabetic complications was partial. There is a need to reorient and motivate health personnels in educating diabetics about self-care. PMID- 9988969 TI - Coronary prone behaviour pattern and risk of coronary heart disease: a case control study. AB - A pair-matched case-control study was carried out at Govt. Medical College Hospital, Nagpur, to investigate association between coronary prone behaviour pattern (CPBP) and coronary heart disease (CHD). The study included 186 cases of CHD and equal number of controls matched for age, sex and socioeconomic status. CPBP identified to be significantly associated with CHD (OR = 3.23, 95% CI 1.73 6.02). The estimates of attributable risk proportion (ARP) and population attributable risk proportion i(PARP) were calculated to the 69.04 (42.19-83.38) and 16.93 (6.25-31.45) respectively. This study thus identified CPBP as a significant risk factor of CHD in this population. PMID- 9988970 TI - Rapid cultivation of Mycobacterium tuberculosis in liquid medium. AB - A total of 894 specimens have been examined by the rapid method for Mycobacterium tuberculosis. The medium used for the rapid isolation was Veeraraghavan's modified medium V (T2). It is a rich synthetic medium consisting of amino acids, salts and vitamins. It enables the growth of mycobacteria within 48 hrs. The study was carried out to compare the results of Veeraraghavan's liquid medium with LJ medium in routine clinical laboratory. The results of this study indicate that the rapid method gives consistently better results than those obtained by the standard method. The results compare well with the findings of Daginawala and Banker. PMID- 9988971 TI - Full time professor and Hon. professor. PMID- 9988973 TI - Current issue in hypertension--ambulatory blood pressure monitoring. PMID- 9988972 TI - Has the Medical Council of India succeeded in its aim of improvement of standard of teaching by implementation of full time teachers in clinical subjects? PMID- 9988974 TI - New, emerging and re-emerging infectious diseases. PMID- 9988975 TI - Malariometry in district Ratnagiri during 1988-1993. AB - Ratnagiri, a coastal district situated in the western part of Maharashtra, is stratified as 'Non-Problem District' as far as Malaria is concerned based on API, topography, rainfall, vector species, Vulnerability etc. Konkan rail project was launched in 1991 and 6 out of 9 blocks of districts Ratnagiri are penetrated by the rail-line. The local ecology of the district is disturbed on account of the project, which is expected to favor malarial transmission. A study based on secondary data was undertaken with following objectives: To assess various operational indicators under NMEP during 1988-93 in the district with respect to their quantitative and qualitative fulfillment. To assess API in the district during same period in the context of inception of Konkan rail. It disclosed that the operational indicators like SPR, SFR & Pf Percentage showed upward trend since 1991 i.e. the year of inception of the Konkan rail project. With ABER consistently above 10% & concordance of the cross-checking results above 96%, the estimate of API becomes more meaningful. Though API shows upward trend, it was never above 2 during 1988-93. Less number of positive cases were found in Active Surveillance during 1988 to 1993. The contribution of Drug Distribution Centres (DDCs) is almost negligible in the district. In-depth analysis of positive cases revealed that the immigrants suffered more & May to July was the season for malaria transmission in the district during the said period. More people above 15 yrs. and more males were found malaria positive which may be because of more outdoor life of this group. Block wise analysis revealed that Mandanged & Khed Blocks showed API more than 2 since 1992. Paradoxically, Mandangad is a coastal block without rail-line, while Khed block is situated away from seashore but has rail-line. More irrigation, less adequate surveillance because of staff vacancy & nonfunctional Drug Distribution Centres (DDCs), more losses to radical treatment are the probable factors responsible for higher API in Mandangad and Khed blocks as compared with the rest of the blocks from the District Ratnagiri. PMID- 9988976 TI - Sociomedical problems of aged population in a rural area of Wardha district. AB - Most of the old persons staying in rural areas are illiterate with physical disabilities and are psychologically disturbed due to the loss of income and hence they are unable to lead a productive life. The present study was thus undertaken in a rural area of Wardha district, with the objective of studying the sociomedical aspects and psychological perceptions of the elderly population. Out of 10,000 population, 600 individuals of age 60 years and above were studied. Proportion of females was 330 (55%) and males 270 (45%) respectively. 300 (66.5%) of them were illiterate, and majority were agricultural labourer (238, 39.66%) and daily labourers (172, 28.66%). 244 individuals (40.67%) were still the head of the family and rest were related to the head of the family. 91 (15.17%) felt the change in attitude of the family members. 139 (31.5%) felt neglected and 146 (24.33%) loneliness respectively. PMID- 9988978 TI - Teenage primigravidae: a comparative study. AB - A review of history sheets of obstetric cases recorded in a district hospital in 1992 was done to compare the obstetric outcome in 200 teenage first pregnancies (Study group) with that in Control group i.e. 20 years to 29 years. It revealed that incidence of complications of pregnancy like anaemia, pregnancy induced hypertension (PIH) and preterm labour were significantly higher among teenage mothers. The normal mode of delivery was commoner in teenagers (82.5%) in comparison to control group (76.5%), probably because of higher number of low birth weight babies. The fetal outcome was significantly worse in teenage mothers with high incidence of perinatal mortality (8%) and low birth weight babies (35%). There was not a single newborn with birthweight above 3500 gms, in teenage group, whereas, control group had 5 babies (2.5%) in the category. PMID- 9988977 TI - Relationship of national highway with injecting drug abuse and HIV in rural Manipur, India. AB - Earlier study reported that about 1% of general population or urban Manipur was injecting drug users (IDUs). A study was conducted to observe the IDU prevalence in rural Manipur and the role of national highway (NH) in determining the IDU prevalence if any. It was also aimed to study the HIV prevalence among IDUs of different villages. Villages were startified in to 3 categories based on distance and communication facilities from the national highway, which cuts across the villages to the neighboring state, Nagaland. Villages close to NH had the highest IDU prevalence of 1.3% and remote villages had the least prevalence of 0.2% whereas villages in between the above mentioned two groups had a prevalence of 0.9%. It was surprisingly observed that HIV was uniformly distributed among the IDUs of all villages and ranged from 50-51%. This indicates that IDU prevalence at distance is predominantly determined by the presence of drug trafficking route/s like national highway whereas HIV prevalence is mainly determined by the needle sharing behaviour of IDUs. PMID- 9988979 TI - Epidemiological correlates of dental caries in an urban slum of West Bengal. AB - The overall prevalence of dental caries was found to be 57.47 percent in an urban slum irrespective of sex, with a maximum of 75.88 percent in the age group of 5-9 years. Habit of taking hard and sticky food, bad oral hygiene were some of the important epidemiological correlates. Fluoride content of drinking water did not show any significant role. PMID- 9988981 TI - Child and adolescent psychiatry in Israel--towards the millennium. PMID- 9988980 TI - Epidemiological study of an outbreak of cholera in Delhi cantonment. AB - An epidemiological study was undertaken to investigate an outbreak of cholera in Delhi Cantonment during May 1991. The study design was a hybrid design using a retrospective Case-Control method superimposed on a population based cross sectional approach. A total of 9 cases of cholera, confirmed in the laboratory as Vibrio cholerae, 0-1, Eltor, Ogawa were identified using population based survey and compared with 33 controls from the same source population. The overall Incidence rate was 0.71% and showed a significant rising trend with age. There was no morality. Assessment of water supply, sanitary conditions of cook houses and disposal system of night soil could not provide any clue to the source of infection. Subsequently, all the food handlers were subjected to rectal swab examination. Two of them, working in the same messes from where cases had occurred, were found positive for Vibrio cholerae (0-1, Eltor, Ogawa). Immediate control measures by way of isolation and treatment of carriers promptly abated the outbreak. Role of carriers in outbreak of cholera has been highlighted. PMID- 9988982 TI - The child suicide potential scale: inter-rater reliability and validity in Israeli in-patient adolescents. AB - The objective of this study was to evaluate the psychometric properties of the Hebrew version of the Child Suicide Potential Scale for use with psychiatrically hospitalized adolescents. The criterion validity, the parallel validity, the internal consistency, the inter-rater reliability and the test-retest reliability were assessed. One hundred eighty-five adolescent in-patients, consecutive admissions to a locked adolescent unit, were interviewed by a single interviewer. The subjects filled out a series of self report questionnaires and were also rated on an observational measure by the ward staff. In addition, 30 adolescents were interviewed by two raters simultaneously, in order to check the inter-rater reliability of this semi-structured interview. Twenty-three of the interviewees were re-interviewed after 6-12 months in order to assess the test-retest reliability. The majority of the Pearson correlation coefficients between the Child Suicide Potential Scale and parallel self report measures were also statistically significant. The internal consistencies of sections in the scale were high. The scale was found to have good parallel validity, by differentiating between suicidal and non-suicidal patients. The Pearson Correlation Coefficients between the two raters were markedly significant. The test-retest reliability was low. These results indicate that the Child Suicide Potential Scale is a reliable and fairly valid tool for the assessment of suicidal behavior in adolescent in patients in Israel. PMID- 9988983 TI - Dyadic psychotherapy for early relationship disorders: a case study. AB - Specific treatment modalities, such as dyadic psychotherapies, have emerged, based on the notion that in cases of very early relational disorders, the patient is the parent-infant relationship. The aim of this paper is to present a case study of such a relational disorder which took place as the result of a complex interplay between the infant's biological risk factors and the parents' psychological risk factors. The emphasis is on the technique and the course of the dyadic psychotherapy of the mother and her three-year-old child, where the main goal was to change some of the intrapsychic and interpersonal processes specifically related to pathological motherhood. The theoretical background is briefly presented, while emphasizing the criteria for choosing one approach among the different kinds of dyadic psychotherapy. PMID- 9988984 TI - Is early intervention effective in preventing ADHD? AB - The purpose of this study was to examine whether early intervention by non pharmacologic means (occupational therapy and speech therapy) can decrease the incidence of ADHD in a group of preschool children at high risk for developing this syndrome. Fifty-one children who suffered at the age of 2-4.5 years from inattention, speech delay and/or motor delay with or without hyperactivity were reexamined at the age of 8-10 years (average 8.9 +/- 1.0 years) by a developmental pediatrician and a developmental psychologist, using the following tests and questionnaires: WISC-R IQ test, Touwen and Prechtl neurological examination for soft neurological signs and the DSM-III-R questionnaire for parents and teachers for the assessment of inattention and hyperactivity. A detailed medical questionnaire was also completed. Of 51 children, 20 (39%) had ADHD. Of these 20 children, 8 had a history of ADHD in other siblings. We found that in children with a family history of this syndrome early intervention reduced the incidence of ADHD at school age although the small numbers limit conclusions and need further replication. PMID- 9988985 TI - Characteristics of patients with schizophrenia successive to childhood attention deficit hyperactivity disorder (ADHD). AB - The goal of this study was to investigate the characteristics of schizophrenic patients with a history of childhood attention deficit hyperactivity disorder (ADHD). The study was performed on 37 adolescent patients meeting the DSM-III-R criteria for schizophrenia and ADHD and 40 controls with schizophrenia only. Schizophrenic patients who were diagnosed in childhood as suffering from ADHD had more prominent developmental disturbances in infancy, more insidious course of schizophrenia, failed to respond to neuroleptics and had poorer outcome as compared to patients with schizophrenia only. The results of this study indicate that schizophrenia subsequent to childhood ADHD has a poor prognosis as compared to schizophrenia only. PMID- 9988986 TI - Validity study of the EDI-2 in Israeli population. AB - This study was designed to validate the EDI-2 (1) in an Israeli population. The sample consisted of 29 anorectic patients and 18 recovering anorectics, recruited from six hospitals, and 67 female control subjects matched by age. Results of the validity study indicate that the translated EDI-2 was reliable and valid. Anorectic patients scored higher than the recovering anorectics on most scales. Recovering anorectics resembled the control subjects on most scales except Perfectionism. PMID- 9988987 TI - Aggression and sexual offense in Asperger's syndrome. AB - Asperger's Syndrome is one of the diagnostic subcategories of pervasive developmental disorders. It is characterized by a defect in reciprocal social interaction, lack of empathy for others and poor non-verbal communication. Antisocial acts, including aggression and sexual offense, are not considered to be common in this disorder. We describe an adolescent with Asperger's Syndrome whose main problems are his violence and sexual offenses. We assume that these symptoms are secondary to his diagnosis of Asperger's as a manifestation of his difficulties with the "theory of mind" of others. This atypical case report is in contrast with the low prevalence of aggression and sexual offense in Asperger's, as reported in the literature. We discuss the reasons for this low prevalence. Our conclusions are based on one case history and a literature review. We call for further research in this field. PMID- 9988988 TI - Multiplex developmental disorder. AB - BACKGROUND: Multiplex developmental disorder is a term that was suggested 20 years ago to describe the onset of developmental deficits in affective modulation, social behavior and social sensitivity combined with thinking disorder with bizarre ideas. With the recent validation of these diagnostic criteria, new interest in this disorder has emerged. METHODS AND RESULTS: We reviewed the background and the difficulties in classifying this subgroup of patients. We also describe a representative case of multiplex developmental disorder and discuss the diagnosis. CONCLUSION: This article emphasizes the importance of investigating this subgroup of patients and encourages reports of such cases in Israel. PMID- 9988989 TI - HIV knowledge, beliefs and sexual behavior of male heterosexual drug users and non-drug users attending an HIV testing clinic in Israel. AB - The aim of the study was to compare HIV-related knowledge, beliefs in self control and sexual behavior of non-drug using and drug using heterosexual men. All individuals attending an HIV testing site during a two-month period were asked to complete a questionnaire anonymously. Data for 49 drug users (DU), most of them non-injectors, were compared to that of 94 non-drug using (non-DU) men with similar education levels (high school or less). Sexual behavior items refer to previous six months. FINDINGS: HIV-related knowledge was reported correctly by the majority of men in both groups, but the DU showed significantly more misconceptions (p < 0.01). Consistent but statistically insignificant lower levels of self-control were reported by the DU. Type of sexual relations and the number of regular sexual partners were not different between the groups: 55% of the DU and 67% of the non-DU were not monogamous. DU had either none or many casual partners (three or more), significantly different from the non-DU. The proportion of DU who never used condoms (65%) was higher as compared to non-DU men (43%, p < 0.05). However, when controlling for type of partnership, this difference was sustained only among monogamous men (82% of DU vs. 42% of non-DU never used condoms, p < 0.05). Condom use was significantly associated with age, HIV knowledge and sexual partnership in the DU. The greater deficiencies in HIV related knowledge, and the prevalence of risk behaviors among DU require intensive individual and group counselling, specifically adapted for the needs and the culture of drug users in Israel and incorporated with social-influence orientated change processes. PMID- 9988990 TI - Effectiveness of psychotherapy. PMID- 9988991 TI - The murder of Yitzhak Rabin. PMID- 9988992 TI - Honoring George Annas. PMID- 9988993 TI - Standards of care and standard form contracts: distinguishing patient rights and consumer rights in managed care. PMID- 9988994 TI - The Patients' Bill of Rights: managed care under siege. PMID- 9988995 TI - The tuberculosis crisis: the deadly consequence of immigration policies and welfare reform. PMID- 9988997 TI - Warning: the imported food you are about to consume may (or may not) be harmful to your health. PMID- 9988996 TI - Hospital conversion revenue: a critical analysis of present law and future proposals to reform the manner in which revenue generated from hospital conversions is employed. PMID- 9988998 TI - Product liability and prescription diet drug cocktail, Fen-Phen: a hard combination to swallow. PMID- 9988999 TI - Navigating between a rock and a hard place: an employer's obligation to reasonably accommodate the disabled in the unionized workplace. PMID- 9989000 TI - Broad statutory language is not ambiguous: the Americans with Disabilities Act applies in state prisons. PMID- 9989001 TI - Measures to control tobacco use: immunity, advertising restrictions, and FDA control as proposed in the failed tobacco settlement. PMID- 9989002 TI - Asymptomatic HIV under the ADA: the invisible, yet legitimate disability. PMID- 9989003 TI - Health care needs and services utilization among sheltered and unsheltered Michigan homeless. PMID- 9989004 TI - Culturally competent professionals in therapeutic alliances enhance patient compliance. AB - Medical training has traditionally focused on diagnosis and treatment of disease, with the notion that if these two factors are satisfactorily managed, the desired outcome will inevitably follow. When it does not, failure is often blamed on patient noncompliance. Failure of patients to return for follow-up visits or comply with medication regimens has been shown to be a major barrier to the delivery of effective medical care. However, effective clinical decision making requires that physicians skillfully address not only the biomedical aspects of diseases and their management, but also the sociobehavorial characteristics of patients. The authors maintain that patient participation is necessary for compliance and that a naturally occurring therapeutic alliance between physician and patient incorporates factors such as lifestyle, family, and living circumstances and an awareness of the culturally unique needs of minority patients. Integration of these factors into professional decision making and practical management plans will enhance patient compliance. PMID- 9989005 TI - Physician perceptions of barriers to care for inner-city Latino children with asthma. AB - This article describes physician perspectives on barriers to quality primary care experienced by inner-city children with asthma and presents policy recommendations to reduce these barriers. The authors interviewed 30 physicians who take care of children with asthma in an inner-city Latino neighborhood, conducted a qualitative analysis of interview themes, and used a consensus group method to recommend policy actions. Inner-city physicians described significant access, quality of care, and other barriers in providing state-of-the-art primary care for asthma. Physicians recommended that eliminating financial barriers to care, including lack of health insurance and/or comprehensive health coverage for necessary medications and equipment, is the most important required policy action. In addition, inner-city physicians recommended that medical care and public health programs provide bilingual education for children with asthma and their families and train primary care physicians about how to provide effective asthma care to children with asthma in the inner city. PMID- 9989006 TI - The three leading causes of death in African Americans: barriers to reducing excess disparity and to improving health behaviors. AB - African Americans suffer disproportionately from several major health problems associated with high morbidity and mortality. The 1985 DHHS Secretary's Task Force Report on Blacks and Other Minorities identified six major disease categories of excess deaths for African Americans compared with whites by applying the lower death rate for whites to the American population. The report provided a stimulus for public and private action to begin to address the health disparities between minority and nonminority populations. This article examines three of the leading causes of death for African Americans and assesses the extent to which the health disparity between African Americans and whites has been reduced. The three leading causes of death for African American males are diseases of the heart, cancer, and HIV infection/AIDS. The conditions are the same for African American females except stroke replaces HIV infection. Three health outcomes measures are discussed: life expectancy, excess death rates, and years of potential life lost. A widening of the gap between the races was found for diseases of the heart and HIV infection for males and for cancer for females. An extensive list of barriers to reducing the disparity are presented from the scientific literature and strategies for reducing the three health problems are recommended. PMID- 9989007 TI - Managed care in rural markets: availability and enrollment. AB - The objective of this research was to test the hypothesis that urban-rural differences in managed care availability and enrollment are primarily due to differences in population socioeconomic and health system characteristics rather than geographic location, population size, or density. These two groups of variables were entered into a regression equation to determine which group could best account for the variance in managed care availability and enrollment. In general, the results of these analyses indicated that socioeconomic and health system characteristics did a much better job of explaining differences in managed care availability and enrollment. Therefore, focusing on factors such as adjacency to metropolitan areas or population size or density in making managed care policy decisions may be less productive than focusing on the socioeconomic and health system characteristics of an area. PMID- 9989008 TI - Norplant utilization in a Latina inner-city population. AB - This study was a consecutive-case series of 138 Latinas (age 16 to 36) who received levonorgestrel implants (Norplant) in a community health center between September 1, 1992, and December 31, 1994, and were observed through September 30, 1997. Continuation rate at one year was 70 percent, and 43, 28, and 22 percent at two, three, and four years, respectively. Average observation time was 32 months. Most frequent reasons for removal were excessive bleeding (34 percent), weight gain (26 percent), hair loss (16 percent), amenorrhea (13 percent), desire for pregnancy (11 percent), and headaches (9 percent). Five women discontinued due to fear of ill effects, four to undergo sterilization. No pregnancies occurred while using the method. Norplant is an effective contraceptive for inner-city Latinas; removal rate was higher than in previous reports. Side effects or fear of side effects led to removal in more than half the patients by two years' use. PMID- 9989009 TI - Integrating Buddhism and HIV prevention in U.S. southeast Asian communities. AB - Asian Pacific Islander communities in the United States have experienced an alarming increase in HIV infection over the past few years, possibly due to a lack of knowledge and the relative absence of appropriate educational interventions. The authors propose a new approach to the development of HIV prevention programs in U.S. southeast Asian communities. This article reviews the cultural and economic factors that may facilitate HIV transmission within these communities. Relying on the basic precepts of Buddhism, the dominant religion of many southeast Asian populations in the United States, the health belief model is utilized to demonstrate how recognizable, acceptable religious constructs can be integrated into the content of HIV prevention messages. This integration of religious concepts with HIV prevention messages may increase the likelihood that the message audience will accept the prevention messages as relevant. This nuanced approach to HIV prevention must be validated and refined through field research. PMID- 9989011 TI - Investigational cancer treatment for children. PMID- 9989010 TI - Termination from Medicaid: how does it affect access, continuity of care, and willingness to purchase insurance? AB - Welfare reform has raised fears that Medicaid recipients will lose coverage, yet efforts to insure the poor via waiver programs may fall short. A telephone sample of 351 enrolled and terminated members of a Medicaid managed care plan based in community health centers were asked about insurance status, source of care, willingness to purchase new insurance, and access. Of terminated families, 78 percent had one member without insurance, 93 percent retained a regular source of care (vs. 96 percent enrolled), and 86 percent retained the same source as before losing coverage. Only 11 percent of uninsured respondents were willing to pay $200 per month and 57 percent to pay $50 per month for replacement coverage, and they were more likely to report problems getting prescription medications and obtaining treatment for serious symptoms and to go without care because of the expense. Access to care is diminished for those who lose Medicaid coverage, even for persons attending community health centers. PMID- 9989012 TI - Parent coping and child distress behaviors during invasive procedures for childhood cancer. AB - This study examines what parents identified as their primary stressor before their child's invasive procedure, what coping strategies were used to manage the stress, what level of distress their children experienced during each phase of the procedure, and whether parents' coping modes were associated with their children's distress. Twenty children with cancer from 3 to 11 years of age and the parent present during the procedure participated in the study. Parents' primary stressors were identified as uncertainty about parent role and anticipating the child's distress during the procedure. Although parents used both emotion-focused and problem-focused strategies for coping with their primary stressors, they primarily relied on emotion-focused strategies. Children experienced the most behavioral distress during the procedural phase, and girls exhibited more distress than boys. The parents' coping modes were not associated with their children's distress, but children of parents whose primary stressor was uncertainty about parent role had higher distress than children of parents whose primary stressor was anticipating the child's distress. The findings related to parents' stressors, their coping strategies, and their children's distress were consistent with previous research. Directions for future research and suggestions for dealing with invasive procedures for childhood cancer are described. PMID- 9989013 TI - Preferences for participation in treatment decision making and information needs of parents of children with cancer: a pilot study. AB - This study was performed to obtain information on parents of children with cancer: (a) what role parents preferred to assume in treatment decision making (TDM); (b) parents' priority information needs; (c) if a relationship existed between TDM preferences and information needs; and (d) if sociodemographic, disease and treatment variables predicted TDM preferences or information needs. A cross-sectional survey was conducted with a convenience sample of 58 parents who had a child less than 13 years of age diagnosed with cancer in the previous year. Instruments included a Sociodemographic, Disease, and Treatment Questionnaire; the Control Preferences Scale for Pediatrics, and an Information Needs Questionnaire. The results showed that parents had systematic preferences about TDM, preferring collaborative followed by passive and active roles. Nine priorities in information needs (highest to lowest) were found: (a) treatments and tests, (b) cure, (c) caring for my child, (d) emotional impact, (e) side effects, (f) physical impact, (g) disease, (h) coping with painful procedures, and (i) impact on the family. Sociodemographic, disease and treatment variables were not predictive of preferences for TDM or information needs. Concrete informational needs take precedence over issues of emotional or family impact or pain. A low Kendall's coefficient (0.07) indicated that parents as a group do not have uniform information needs. Information giving must be individualized. PMID- 9989014 TI - Siblings of children with cancer: a review of the literature. AB - Research on siblings of children with cancer during the past 40 years has clearly shown that the childhood cancer experience is a stressor that may increase subjective feelings of stress by well siblings and in some cases lead to decreased psychosocial competencies and increased psychopathologies. Research has expanded from identifying psychosocial problems experienced by the sibling after the patient's death to identifying stressors during the illness experience. More recent studies have been targeted at identifying what action siblings take to cope with the stressors imposed since the cancer diagnosis and have addressed what interventions pediatric oncology nurses use in clinical practice to provide support to siblings of children with cancer. The current state of this body of literature, a review of 18 studies, is presented in this article along with a critique of the research studies and suggestions for future research. PMID- 9989015 TI - Conceptual understanding of resilience in the adolescent with cancer: Part I. AB - During the past two decades, increased research attention has been directed toward understanding the adolescent who is confronted with challenges such as poverty or substance abuse. Accordingly, pediatric oncology nurse researchers and clinicians are increasingly becoming interested in understanding the experience of resilience in the adolescent with cancer. Research and clinical reports have shown that many adolescents with cancer are resilient even though they experience multiple stressors. That is, even in the face of adversity, they develop into well-adapted individuals. The purpose of this article is to develop a conceptual understanding of resilience in adolescents with cancer. Areas that are addressed include the following: (a) an historical overview of the major theoretical paradigms used to understand the pediatric cancer experience; (b) a summary of definitional issues related to the construct of resilience; and (c) a conceptual model of resilience. New insights are provided that may lead pediatric oncology nurse researchers and clinicians to examine resilience in the adolescent with cancer from a variety of perspectives. PMID- 9989016 TI - Becoming a cancer patient: a study of families of children with acute lymphocytic leukemia. AB - This grounded theory study was designed to explore the process by which families of children with acute lymphocytic leukemia (ALL) "become" cancer patients. Data were obtained through interviews with four families and three professional caregivers and were analyzed for processes by which families experience the illness of ALL. The central process of "becoming" was defined as trying to live as "normally" as possible; accepting that life is not the same; understanding what you have to do; and accepting what you can't change/living with dissatisfactions. This process was mediated by families' external contexts, including marital relationships and support networks, experiential contexts, including positive and negative experiences during treatment and previous illness experiences, and internal contexts, including personal survival strategies and personal outlooks and attitudes. The process illustrates the pattern of experience that occurs in families faced with the diagnosis of their child's ALL. Understanding this process may be useful to care providers when treating children with cancer. PMID- 9989017 TI - Swimming and central venous catheter-related infections in the child with cancer. AB - Although there have been many studies evaluating risk factors for catheter related infections in children with cancer, none have examined whether swimming presents such a risk. Families of children with cancer were asked about specific swimming practices and central line care to determine whether there is an association between swimming and infection. Parents completed a self-report questionnaire and medical records were reviewed to document catheter-related intraluminal, tunnel, and exit-site infections. Ninety-one children with a total of 101 tunneled catheters participated in the study. Forty-nine children with a total of 50 catheters were swimmers; 46 children with 51 catheters were nonswimmers (four children had two catheters and swam with one catheter but not the other, therefore, these children were counted twice). There were no statistically significant differences in rates of catheter-related infections between the two groups (0.04/catheter-month in swimmers versus 0.25/in non swimmers, relative risk; RR = 1.6, p = .16). When the analysis was confined to summertime infections per summertime catheter month, there were no significant differences in the rates of infections per summer month (0.06 for swimmers vs. 0.05 for non-swimmers, RR = 1.4; p = .50). When the analyses were performed to compare frequent swimmers with infrequent/non-swimmers, once again there were no differences found in rates of catheter-related infections between the two groups. These results suggest that swimming does not increase the risk of catheter related infections in children with tunneled catheters. PMID- 9989018 TI - The cognitive determinants of performance on the Austin Maze. AB - This study aimed to investigate which abilities are measured by the Austin Maze. One hundred and eight university students were administered a battery of eight neuropsychological tests including, the Austin Maze, the Tower of London, the Wisconsin Card Sort Test, Block Design, the Visual Spatial Learning Test, Digit Span Backwards, the Brown-Peterson Task and the Wide Range Achievement Test of Reading. Results indicated that visuospatial ability and memory both significantly contributed to performance on the Austin Maze, but differed in the degree to which they explained the performance depending on which measure of maze performance was employed. It appears that visuospatial ability is measured in early trials of the Austin Maze when individuals are orienting themselves to the path. In later trials individuals must call upon visuospatial memory to consolidate the details of the path. Executive function and working memory were not found to be significantly implicated in performance on the Austin Maze. PMID- 9989019 TI - Neuropsychological functioning in cocaine abusers with and without alcohol dependence. AB - Thirty codependent cocaine and alcohol users were compared with age-, education-, race-, and sex-matched cocaine abusers (N = 30) and normals (N = 30) using an extended Halstead-Reitan Neuropsychological Test Battery to determine whether cocaine abusers with alcohol dependence were more cognitively impaired than singly addicted cocaine abusers. Tests were grouped and analyzed according to 8 major ability areas. Participants who abused both cocaine and alcohol did not differ from normals on the majority of test measures. An unexpected but consistent finding was the poorer performance of the cocaine sample relative to cocaine and alcohol abusers on measures of complex psychomotor and simple motor functioning (ps < .001). Pure cocaine abusers, but not abusers of both cocaine and alcohol, also performed more poorly than normals on a measure of global neuropsychological functioning (p < .01). These results are consistent with previous reports of generally mild cognitive dysfunction in cocaine abusers. The findings also suggest that cocaine and alcohol abusers of relatively young ages may be less cognitively impaired than demographically comparable cocaine abusers. Evidence from studies of vascular functioning in abusers of cocaine and alcohol alone and in combination is discussed as possible explanation for these findings. PMID- 9989020 TI - Consistency of handwriting movements in dementia of the Alzheimer's type: a comparison with Huntington's and Parkinson's diseases. AB - Patients with dementia of the Alzheimer's type (DAT) and their matched controls wrote, on a computer graphics tablet, 4 consecutive, cursive letter 'l's, with varying levels of visual feedback: noninking pen and blank paper so that only the hand movements could be seen, noninking pen and lined paper to constrain their writing, goggles to occlude the lower visual field and eliminate all relevant visual feedback, and inking pen with full vision. The kinematic measures of stroke length, duration, and peak velocity were expressed in terms of consistency via a signal-to-noise ratio (M value of each parameter divided by its SD). Irrespective of medication or severity, DAT patients had writing strokes of significantly less consistent lengths than controls', and were disproportionately impaired by reduced visual feedback. Again irrespective of medication or severity, patients' strokes were of significantly less consistent duration, and significantly less consistent peak velocity than controls', independent of feedback conditions. Patients, unlike controls, frequently perseverated, producing more than 4 'l's, or multiple sets of responses, which was not differentially affected by level of visual feedback. The more variable performance of patients supports a degradation of the base motor program, and resembles that of Huntington's rather than Parkinson's disease patients. It may indeed reflect frontal rather than basal ganglia dysfunction. PMID- 9989021 TI - Performance discrepancies on the California Verbal Learning Test-Children's Version in the standardization sample. AB - The standardization data for the California Verbal Learning Test-Children's Version (CVLT-C) were used to evaluate statistically significant discrepancies between key quantitative variables of this instrument, as well as the base rate of specific discrepancies. The results indicated that apparently large discrepancies between the respective standard scores were actually fairly common. However, for 3 of the 4 contrasts, discrepancies that equaled or exceeded 1.5 z score points in the hypothesized direction were sufficiently unusual to be considered clinically significant. For a 4th contrast, discrepancies that equaled or exceeded 1 z-score point in the hypothesized direction appeared to meet this criterion. It is suggested that the interpretation of clinically obtained CVLT-C profiles should focus primarily on specific quantitative variables, with inclusion of consideration of the presented base rates of discrepancies between the respective z scores. PMID- 9989022 TI - Emotion processing in the visual and auditory domains by patients with Alzheimer's disease. AB - The ability to process emotional information was assessed in 42 individuals: 23 patients with Alzheimer's disease (AD) and 19 healthy elderly controls. Four tasks assessed the ability to recognize emotion in audiotaped voices, in drawings of emotional situations, and in videotaped vignettes displaying emotions in facial expression, gestures, and body movements. Hemispheric dominance for processing facial expressions of emotions was also examined. There were no consistent group differences in the ability to process emotion presented via the auditory domain (i.e., nonverbal sounds, such as crying or shrieking, and speech prosody). Controls were, however, significantly better than the AD patients in identifying emotions depicted in drawings of emotional situations and in videotaped scenes displaying faces, gestures, and body movements. These differences were maintained after statistically adjusting for the visuospatial abilities of the participants. After a statistical adjustment for abstraction ability, some of the tasks continued to differentiate the groups (e.g., the emotional drawings task, the videotaped displays of faces), but others did not. These results confirm and extend previous results indicating that AD patients do not have a primary deficit in the processing of emotion. They suggest that the difficulties of the AD patients in perceiving emotion are secondary to the cognitive impairments associated with AD. PMID- 9989023 TI - Neuropsychological test performance in the acquired immunodeficiency syndrome: independent effects of diagnostic group on functioning. AB - Individuals infected with the acquired immunodeficiency syndrome (AIDS) are at risk for developing cognitive impairment. The extent to which the impairment represents the results of a single factor accounting for a wide degree of cognitive dysfunction, or is the result of the combined effects of multiple factors, has not been determined. In the present study, we analyzed data from 134 patients with AIDS and 105 HIV- controls using a recently developed analytical procedure. The results revealed that, by and large, the test variables shared a significant amount of variance related to disease status. Hence the AIDS-related influences on cognition are shared and thus cannot be considered independent. Two tests, Digit Symbol Substitution, and the primary measure of verbal free recall, had a direct relationship with the group variable (AIDS vs. controls). These results suggest that a single factor is sufficient to account for a large proportion of the AIDS-related variance on a wide variety of neuropsychological tests. PMID- 9989024 TI - A prospective analysis of the recovery of attention following pediatric head injury. AB - Little is known about specific attentional sequelae following a closed head injury, their pattern of recovery or their interaction with ongoing development. The present study examined attentional abilities in a group of children who had sustained a mild, moderate, or severe head injury. Results showed that the severe head injury group exhibited greater deficits on a number of attentional measures at acute and 6 months postinjury phases, in comparison to children in the mild and moderate head injury groups. Specifically, deficits were most evident on timed tasks where speed of processing was an integral component. Difficulties persisted to at least 6 months postinjury and so may lead to cumulative deficits over time. PMID- 9989025 TI - Cognitive outcome in children and adolescents following severe traumatic brain injury: influence of psychosocial, psychiatric, and injury-related variables. AB - Previous studies of childhood traumatic brain injury (TBI) have emphasized injury related variables rather than psychiatric or psychosocial factors as correlates of cognitive outcomes. We addressed this concern by recruiting a consecutive series (N = 24) of children age 5 through 14 years who suffered a severe TBI, a matched group who sustained a mild TBI, and a second matched group who sustained an orthopedic injury. Standardized intellectual, memory, psychiatric, family functioning, family psychiatric history, neurological, and neuroimaging assessments were conducted at an average of 2 years following injury. Severe TBI, when compared to mild TBI and orthopedic injury, was associated with significant decrements in intellectual and memory function. A principal components analysis of independent variables that showed significant (p < .05) bivariate correlations with the outcome measures yielded a neuropsychiatric factor encompassing severity of TBI indices and postinjury psychiatric disorders and a psychosocial disadvantage factor. Both factors were independently and significantly related to intellectual and memory function outcome. Postinjury psychiatric disorders added significantly to severity indices and family functioning and family psychiatric history added significantly to socioeconomic status in explaining several specific cognitive outcomes. These results may help to define subgroups of children who will require more intensive services following their injuries. PMID- 9989026 TI - Reorganization of verbal memory and language: a case of dissociation. AB - Left-to-right reorganization of verbal memory following early left hemisphere damage has been reported in patients whose expressive language is governed by the right hemisphere. We present a case in which verbal memory performance was intact, despite severe left mesial temporal damage, and despite aphasia on left internal carotid sodium amytal ablation. The distribution and degree of left mesial temporal damage was assessed visually and quantitatively on MRI. These findings raise the possibility that verbal memory may shift to the language nondominant hemisphere as a result of early left mesial temporal damage. PMID- 9989027 TI - To see better to the left when looking more to the right: effects of gaze direction and frames of spatial coordinates in unilateral neglect. AB - Unilateral spatial neglect entails a failure to detect or respond to stimuli in the space opposite to a brain lesion. However, the contralesional hemispace can be determined by different frames of spatial coordinates, such as eyes-, head-, body-, or environment-centered coordinates. We observed 2 patients with a right hemisphere stroke whose left spatial neglect was modulated by distinct coordinates systems depending on the task. Four tasks were given in different conditions of central gaze and either the eyes or the head rotated 30 degrees to the right or 30 degrees to the left. While the 2 patients had a retinotopic defect in 1 visual field quadrant that remained the same irrespective of gaze direction (upper or lower quadrant in 1 case each), the other quadranopic field defect improved with eyes rotation to the right but not with head rotation, suggesting a head-centered spatiotopic deficit. Performance on line bisection was influenced both by eyes and head rotation, as well as by the position of the lines with respect to the trunk midline, suggesting the involvement of both head centered and body-centered coordinates. Visual imagery and auditory extinction were not modified by changing the eyes or head position. These findings suggest that distinct spatial coordinates are brought into play depending on the tasks demands. PMID- 9989028 TI - Factors affecting performance in cross-cultural neuropsychology: from a New Zealand bicultural perspective. PMID- 9989029 TI - Span of temporal continuity as a measure of personal and present existence. PMID- 9989030 TI - [The evaluation of pathogenic factors in duodenal ulcers]. AB - There were examined 90 patients with severe course of duodenal ulcer disease. In 83% of patients the atropinedependent reaction of acid production was noted, giving evidence the dominant influence of neural regulation on gastric secretion, in 17%--atropineresistant reaction, giving evidence the hormonal mechanism of regulation. PMID- 9989031 TI - [The role of the extracorporeal detoxication in prophylaxis and treatment of respiratory disorders in patients with acute ileus]. AB - Hemosorption (HS) and plasmapheresis (PA) stimulate significantly the pulmonary metabolic functions due to their potent detoxicational effect. Arterial hypoxemia occurs simultaneously. The PA application contra HS causes more durable and stable detoxicational effect. It is mandatory in patients with an acute ileus to combine the HS conduction and repeated sessions of spontaneous respiration with end-expiratory additional pressure and to include fatty emulsions in complex of substitutional therapy while PA application. PMID- 9989032 TI - [Non-favorable prognosis of the postop period and early diagnosis of postop peritonitis]. AB - After the operation peritonitis have occurred in 19 patients, in 40- postoperative period course was without complications. The informativity of the laboratory investigations indexes for the postoperative course prognosis and early peritoneal cavity inflammation was revealed. PMID- 9989033 TI - [Prophylaxis of postop bronchopulmonary complications during surgical treatment of inflammatory diseases of hepatobiliary tract]. AB - The combination of own breathing with heightened end-expiratory pressure and antibiotic prophylaxis, ultrasonic inhalation using proteolytic enzymes, bronchofibroscopic sanation have permitted to reduce the occurrence frequency of pulmonary complications from 16 to 7%. PMID- 9989034 TI - [Results of hemoroidectomy with the use of staplers]. AB - Hemorrhoidectomy was conducted in 222 patients: in 121 (1st group)--according to Milligan--Morgan method, in 101 (2nd group) using bronchial stump suture appliance and lung hilum suture appliance apparatuses. Of the first group patients in 32.2% a pain syndrome was noted, in 21.4%--a disuric disorders, in 9.9%--perianal oedema, in 3%--hemorrhage. In the second group complications were absent. PMID- 9989035 TI - [Varieties of vascular anastomoses in the course of renal allotransplantation]. AB - The results of conduction of 305 renal transplantation operations are adduced. Ultrasonic dopplerography ought to be applied in complex of preoperational examination of potential recipient. Maximal usage of the donors kidney with atypical vascular pedicle structure is mandatory and possible. In the cases of the main line type of the vessels structure, while other equal conditions present, the end to end anastomosis formation with a. iliaca internal is preferable. The ligature of vessel above and below to the defect is a single effective method of treatment of secondary arrosive hemorrhage from a, iliaca externa. PMID- 9989036 TI - [The ureter's modeling during ureterocystoneostomy]. AB - While complex examination of patients with megaureter in late stages it was established the afection in the first place of the ureter's muscular layer and the disorder of its contractice capacity. The causes of megaureter's occurrence were: obstruction of the ureter's intramural portion and vesico-ureteric reflux. Longitudinal resection of megaureter was conducted in 25 patients, the longitudinal ureter's fold formation--in 6, intraureteric plasty was done in 28. In 93% of observations the intraureteric plasty efficacy was noted. PMID- 9989037 TI - [The puncture laser dissectomy application for the discogenic lumbosacral radiculitis]. AB - The puncture laser discectomy was conducted in 273 patients with discogenic lumbosacral radiculitis while the conservative therapy inefficacy, pain syndrome in a lumbago stage present and lumboischialgia with absent prominent locomotive disorders and if the intervertebral disc hernia has the size up to 0.6 cm. PMID- 9989038 TI - [Comparative evaluation of suture material used in the treatment of patients with peritonitis]. AB - The advantages of application of letilan-lavsan and octselon versus kapron were noted in 85 patients operated on for purulent peritonitis. PMID- 9989040 TI - [Application of the staged radical operation for obstruction colonic cancer]. AB - The results of treatment of 202 patients with an acute ileus due to colonic malignancy are adduced. The total five year survival index was 20% and a ten year one--1.5%. PMID- 9989041 TI - [The application of colored liquid-crystallic thermography in diagnosis of gastric cancer]. AB - The efficacy of application of colour liquid crystallic thermography in the gastric cancer diagnosis was studied. The method permits to establish localization and spreading of gastric malignancy, excels by informativity in the diagnosis complex and treatment monitoring of patients. PMID- 9989039 TI - [Abdomino-anal resection of rectum with hemi-resection of anal canal]. AB - The method of performing of abdominoanal rectal resection with anal hemiresection for tumor, localized in inferoampullar rectal portion and spreading on anus. PMID- 9989042 TI - [Diagnosis and surgical treatment of patients with insulinoma]. AB - The experience of treatment of 116 patients with the organic hyperinsulinism syndrome is presented. PMID- 9989043 TI - [Risk factors determining the outcome of a diffuse peritonitis of appendicular genesis in children]. AB - The peculiarities of pre-, intra- and early postoperative period course in 108 children, operated on for diffuse and general peritonitis of appendicitis origin, are studied. Most significant 34 prognostic factors for the disease outcome are choosed. The leading factors are the disease course duration, general condition of the patient while hospitalization, the vegetative disorders presence, the intestinal paresis degree, the biochemical inductors of stress contents, the peritoneal exudate character, the kind and composition of microorganisms in it, the character of an early postoperative period course. PMID- 9989044 TI - [Common biliary duct cyst in children]. AB - Eight children with the cyst of choledochus, ageing from 1 month to 15 years, were treated for the period of 20 years in clinic. Cystoduodenostomy is the method of choice for the treatment. All the patients have recovered. PMID- 9989045 TI - [Isolated invagination of appendix in girls]. AB - The experience of treatment of 15 children with isolated invagination of processus appendicularis was summarized. The clinic, diagnosis, principles of operative treatment were analyzed. PMID- 9989046 TI - [Clinical course, diagnosis and treatment of ovarian tumors and cysts in children]. AB - The experience of diagnosis and treatment of the ovarial tumor and cyst in 68 girls was summarized. Children were admitted to the hospital with an acute abdomen signs and in a planned order as well. All the patients were operated on. Children with benign ovarial tumor and cyst are alive. Four patients with malignancy have died. PMID- 9989047 TI - [Experimental substantiation of a two-staged method of microsurgical transplantation of the complex composite flaps]. AB - The authors have proposed two-staged flap transplantation, consisting of flap mobilization on vascular pedicle with subsequent its transplantation in several days. In experiment on muscular flaps, obtained from regio epigastrica of 30 rabbits, it was established that optimal time for the second stage of operation conduction may be end of the second--beginning of the third day after the transplant mobilization. PMID- 9989048 TI - [The ways of students' training optimization in hospital clinic]. PMID- 9989049 TI - [Comparative estimation of results of palliative and radical operations conducted on gastroduodenal ulcer complicated by perforation]. PMID- 9989050 TI - [New classification of malignant tumors TNM (5th edition)]. PMID- 9989051 TI - [Contemporary concepts of the problem of hydrocephaly]. PMID- 9989052 TI - [The application of color doppler sonography in contemporary mammary studies]. PMID- 9989053 TI - [The incidence of thyroid gland diseases among the population of the Ukraine]. PMID- 9989054 TI - [The method of intraoperative intestinal dialysis in peritonitis]. PMID- 9989055 TI - [Mallory-Weiss syndrome as one of the causes of gastric hemorrhage]. PMID- 9989056 TI - [Successful treatment of necrotic enteritis under the conditions of a central regional clinic]. PMID- 9989057 TI - [The incidence of intramural duodenal abscess as a complication of cholelithiasis]. PMID- 9989058 TI - [The peritoneal irritation symptom in the diagnosis of acute appendicitis in obese patients]. PMID- 9989059 TI - [Rare observation of an acute appendicitis in the aborted colonic turning]. PMID- 9989061 TI - [Enterogenic cyst in the mediastinal and retroperitoneal space with penetration into the lungs in a newborn baby]. PMID- 9989060 TI - [Acute phlegmonous appendicitis in the early period after the prostate gland excision]. PMID- 9989062 TI - [Combined hemorrhoids in early childhood]. PMID- 9989063 TI - [Femoral hernia in a child]. PMID- 9989064 TI - [The observation of splenic rupture in a newborn child]. PMID- 9989065 TI - [The observation of fistula from the sigmoid colon diverticulum into the bladder]. PMID- 9989066 TI - [The efficacy of complex treatment of an acute calculous pyelonephritis]. PMID- 9989067 TI - [The use of uroflowmetry in phimosis in children]. PMID- 9989068 TI - [The injury of abdominal and thoracic cavities with a metallic hook through the perineum]. PMID- 9989069 TI - [The choice of surgical approach in the resection of abdominal aorta]. AB - The abdominal aorta aneurism (AAA) surgery experience in 110 patients was analysed. The topographic-anatomic investigations were conducted, a new surgical access to suprarenal and infrarenal AAA parts was proposed. PMID- 9989070 TI - [Changes in the central hemodynamics in the surgical treatment of abdominal aorta aneurysm]. AB - The algorythm of examination and treatment of patients with an abdominal aorta aneurysm was proposed. PMID- 9989071 TI - [Simultaneous revascularization of the myocardium and lower extremities due to dissipated atherosclerosis]. AB - In 18 patients with the cardiac coronary arteries and the lower extremities main arteries atherosclerotic affection the simultaneous aortocoronary shunting in concurrence with the lower extremities revascularization were conducted. The mortality was 5.5%. PMID- 9989072 TI - [The application of lumbar sympathectomy in complex of treatment of obliterating atherosclerosis]. AB - The lumbar sympathectomy was conducted for the grade II (according to Fontaine) obliterating atherosclerosis of the lower extremities arteries in 309 cases as the main method of surgery, and in 426--in concurrence with reconstructive intervention on the main vessels. The indications for and the efficacy of the desympathization in various levels of the main arterial bed affection are discussed. PMID- 9989073 TI - [Remote follow-up results of the surgery in patients with unspecified aortoarteritis]. AB - In 133 patients with nonspecific aortoarteritis 172 operations were conducted, 83.8% of them--reconstructive interventions. In 29 patients with isolated affection of truncus brachiocephalicus 32 operations were conducted. Good results of up to 13-year follow-up was 77%, mortality--13.8%. For the isolated affection of aortal arch in 26 patients 27 operations were conducted. Five-year survival have constituted 100%, of them in 79.9% good result was observed. For the isolated affection of aorto-femoral segment 38 patients were operated on. Up to 8 year follow-up was achieved in 32 of them, good result was noted in 73.1%. For the combined affection in 40 patients 51 operations were done. Seven-year follow up was achieved in 36 patients, good result was noted in 74.2%. PMID- 9989074 TI - [Combined treatment of patients with affected extracranial segment of the internal carotid artery]. AB - The results of examination of 84 patients with extracranial a. carotis externa affection were analysed. In 36 patients the combined treatment was conducted, including surgical intervention and postoperative therapy course. PMID- 9989075 TI - [Surgical treatment of symptomatic arterial hypertension]. AB - During ten years 57 patients with symptomatic arterial hypertension were examined. The suprarenal gland disease was diagnosed in 31 patient, the renal arteries disease--in 16, the thoracic aorta coarctation--in 10; 35 patients were operated on. The radical intervention conduction have promoted the arterial pressure normalization in early postoperative period. PMID- 9989077 TI - [Combined treatment of purulent complications of diabetes mellitus]. AB - The results of treatment of 132 patients with the type I diabetes mellitus of middle end critical severity, trophic disorders and purulent-necrotic complications were analysed. Clinical efficacy of intravascular laser irradiation of blood, the prolongated medicinal intraarterial infusion, antioxidant therapy were established. PMID- 9989076 TI - [On the legal aspects of the term "diabetic angiopathy of the lower extremities". Part I. Clinico-morphological parallels of the lower diabetic angiopathy]. AB - The clinico-morphological data analysis was done in 100 examined patients with diabetic angiopathy of the lower extremities. The morphological changes revealed have corresponded to severity of the disease clinical symptoms in 70% only. Purulent affection of extremities have characterized not the end stage of angiopathy only but it was observed in another stages of the disease. PMID- 9989078 TI - [Surgical treatment of an acute thrombophlebitis of the varicose veins of the lower extremities]. AB - The operation for an acute thrombophlebitis of the lower extremities varicose veins was conducted in 45 patients in an acute period of complication (1st group); in 22--after the durable ambulatory conservative therapy (2nd group); in 18--hospitalized for the next aggravation of the superficial veins chronical recurrent thrombophlebitis (3d group). Complications after the operation have occurred in the 1st group in 4.4% patients, in the 2nd group--in 13.6%, in the 3d group--in 22.2%. The duration of treatment of patients in stationary have constituted on average accordingly 7.6, 9.3 and 23.5 days. In elderly patients, having severe concurrent diseases, the segmental phlebothrombectomy conduction is indicated. PMID- 9989079 TI - [The results of combined surgical treatment of the occlusive forms of the deep vein thrombosis with the trophic ulcers in the lower extremities]. AB - The results of treatment of 156 patients with occlusion forms of the deep veins thrombosis of the lower extremities and trophic ulcers are adduced. The partial or complete thrombectomy the shunting, Linton and Cockett operations, plastic interventions, the pulmonary artery embolism prophylaxis were conducted, and the late terms--the vibro- and hydromassage. PMID- 9989081 TI - [Congenital heart diseases in adults]. AB - The experience of treatment of 45 adult patients with the innate heart diseases was summarized, 33 of whom were operated on. The interatrial septum defect closure was conducted in 14 patients, aortal valvotomy--in 1, the valve change for the twocuspid aortal valve (AV)--in 5, the aortal coarctation correction--in 3, the coronary arteries anastomosis formation with the coronary-pulmonary arterial fistula ligature--in 3, valvotomy or the balloon dilatation of pulmonary artery--in 2, septal myectomy for hypertrophic cardiomyopathy--in 2, the intervention on two- or three-cuspid valve or AV for the open left upper cava vein--in 2, AV in Marfan's syndrome--in 1. There were no postoperative mortality or complications. Of 8 nonoperated patients in 5 the cerebral blood circulation disorder have occurred, caused by paradoxical emboli. Thirty five year old woman with Eisenmenger syndrome have died. The patients with atresia of right pulmonary veins and fibrosis of right lung have survived up to the fourth decade of life. PMID- 9989080 TI - [The treatment of an acute thrombophlebitis of subcutaneous veins of the foot: an current surgical problem]. AB - The results of treatment of 1225 patients with an acute subcutaneous foot veins thrombophlebitis were analysed. Morphological changes of the vein wall were studied up, bacteriological investigation of the thrombosed veins was conducted. PMID- 9989082 TI - [Microsurgical replantation of the main segments of the extremities]. AB - Of 61 injured person, to whom the replantation of the extremity's large segment was conducted, the replantated segment revivement was noted in 43 (83%). The acceptable functional rehabilitation of the extremity was achieved in 38 (88.4%) patients due to conduction of various correcting interventions in late postoperative period. PMID- 9989083 TI - [Experimental-morphological and clinical basis of preventive methods for the intraoperative complications of the amputation of the lower extremity at the thigh level]. AB - The nonexpediency of the tourniquet and retractor application while the extremity amputation conduction on the femur level, the necessity in renunciation of the neurotomy conduction using an amputational knife, scalpel or scissors were proved, basing on the topographic-anatomic (53 cadavers), experimental (130 white rats and 50 dogs) and clinical (40 patients) data. PMID- 9989084 TI - [The method of integral estimation of a functional status of the hemostatic system]. AB - The instrumental method of the integral assessment of functional state of the hemostasis system using piezoelectric hemoviscosigraphy was elaborated. PMID- 9989085 TI - [The treatment of intra-abdominal abscess]. AB - The experience of treatment of 18 patients with intraabdominal abscess using the regional laparostomy conduction and introducing nitazol, immobilized on polymethylsiloxane, in the abscess cavity, was summarized. PMID- 9989086 TI - [Endolymphatic analgesia after the surgery for an acute mechanical ileus]. AB - It was established in experiment that, while endolymphatic infusion of analgin with droperidol, the maximal analgin concentration in central lymph, blood and cerebrospinal fluid holds out much longer than while intramuscular injection. In 39 patients, operated on for an acute mechanical ileus, the endolymphatic analgin and droperidol infusion have permitted to achieve a stable anesthesia. PMID- 9989087 TI - [Morpho-functional aspects of pathogenesis and surgical treatment of the abdominal wall hernia in elderly and senile patients]. AB - The abdominal wall tissues atrophy was revealed while histological and electromyographic investigation in 16 patients with primary hernia (the mild one) and in 17--with secondary, recurrent and postoperative (much more significant atrophy). The data obtained are applied for the choice of optimal method of operation conduction. PMID- 9989088 TI - [Etiology, pathogenesis and treatment of severe recurrent forms of erysipelas of the lower extremities]. AB - The experience of treatment of 314 patients with erysipelas was summarized. The organizational principles of struggle against this disease are proposed. PMID- 9989089 TI - [Remote follow-up results of application of extracorporeal methods of treatment of the patients with bronchial asthma]. AB - The questionnaire data of 860 patients with bronchial asthma (BA) and the 7-year catamnestic investigation depth were analysed. According to clinical effect achieved the extracorporal methods of the patients with BA treatment were ranked in such a manner: splenosorption, immunosorption to DNA, which contains the sorpents, the conventional method of hemosorption (HS), using the SKN sorpent, plasmapheresis and the ultra-violet irradiation of blood (UVIB). The applicational efficacy of HS using KAU and "Gemosfer" sorpents is significantly lesser than such of SKN sorpents. UVIB do not effects late follow-up results of the hormonally-dependent patients treatment. PMID- 9989090 TI - [Diagnosis of multiple abscesses of the brain]. AB - It was established, basing on the data obtained while examination of 64 patients with multiple brain abscesses, that computer and magneto-nuclear resonance tomography are the most informative in detection of localization, number and the course phase. PMID- 9989091 TI - [Surgical treatment of fractures of long bones in a patient with multiple injuries]. AB - The authors recommend application of the intramedullary and extracortical osteosynthesis methods while the trauma severity constituting less than 25 marks according to the ISS scale, the extracortical one--in 25-40 marks, and the external one--in more than 40 marks. Three patients died after the early conduction of osteosynthesis and 15--after the postponed one of the whole 315 operated injured persons with polytrauma. The miniinvasive extracortical osteosynthesis using the minimal contact plates, the intramedullary osteosynthesis using the rods with the hightened rotational stability and the external osteosynthesis using pivotal apparatuses were applied for the long bones fractures treatment. PMID- 9989093 TI - [The teaching concepts in general surgery]. PMID- 9989092 TI - [Conceptual aspects of emergency care rendered to injured people with injuries]. PMID- 9989094 TI - [Direct revascularization in chronic ischemia of the lower extremities]. PMID- 9989095 TI - [The principal mechanisms of thrombosis (report I). Mechanisms of vascular wall thromboresistance]. PMID- 9989096 TI - [Preventive methods of operative wound abscesses in patients with peritonitis]. PMID- 9989097 TI - [The first experience with anti-tachycardiac electric stimulator]. PMID- 9989098 TI - [Observation of x-ray surgical occlusion of the patient's own liver artery in a patient with post-traumatic hemobilia]. PMID- 9989099 TI - The management of variceal bleeding: past, present and future. AB - The basic principles of managing variceal bleeding have changed little in the last fifty years. Fluid resuscitation, efforts to induce intra-variceal thrombosis, and treatments to reduce portal pressures remain the keys to successful therapy. However, the last decade has seen the introduction of new modalities which have improved treatment efficacy and safety. Octreotide and, at many institutions, terlipressin have supplanted intravenous vasopressin as acute pharmacologic therapy for variceal bleeding. Endoscopic management of variceal bleeding now includes endoscopic variceal ligation in addition to the widely practiced endoscopic sclerotherapy. Placement of transjugular intrahepatic portosystemic shunts has been proven to be a reliable means of emergently inducing a reduction in portal pressure and stopping variceal hemorrhage. In the out-patient setting, therapy with non-selective beta-blockers, often coupled with oral nitrates, is increasingly accepted as a means of improving portal hypertension and reducing a patient's risk of first hemorrhage or recurrent variceal bleed. This review focuses on the history and evolution of management strategies for variceal bleeding, discusses the physiologic basis for each type of therapy, summarizes current treatment approaches, and addresses recent developments in the field. PMID- 9989100 TI - Past, present and future of end-stage renal disease therapy in the United States. AB - Dialysis was first described and used in 1854 to separate substances in aqueous solution based on different rates of diffusion through a semipermeable membrane. In vivo hemodialysis was performed in animals early in the twentieth century. Hemodialysis was first carried out in patients with acute renal failure in The Netherlands during the Second World War and in the United States in 1948. Repetitive hemodialysis for the treatment of chronic renal failure due to end stage renal disease had to await the development of an acceptable long-lasting vascular access in 1960. The subsequent successful development of a technique to create an adequate arteriovenous fistula in 1972 permitted the rapid growth of dialysis programs, when the cost of this therapy was largely paid for by Medicare. Equipment has been developed to foster home-care hemodialysis and chronic ambulatory peritoneal dialysis. Enhancements in renal replacement therapy included the availability of recombinant human erythropoietin, calcitriol, and effective antihypertensive drugs. Technical advances in hemodialysis followed the use of bicarbonate dialysate, more biocompatible membranes, membranes of higher porosity, and ultrafiltration. Questions remain regarding the evaluation of the adequacy of dialysis which is to be achieved or prescribed. Careful attention to the management of the patient with progressive chronic renal insufficiency is crucial in dealing with the inevitable onset of uremia and the initiation of dialysis and/or renal transplantation. The cost of renal replacement therefore represents a great societal burden. A better understanding of how to prevent onset and progression of specific nephropathies along with the availability of new and more effective equipment for renal replacement therapy has a high priority. PMID- 9989101 TI - Twelve-year experience with expanded polytetrafluoroethylene in the repair of abdominal wall defects. AB - BACKGROUND: A prosthetic device must be used to repair ventral hernias in patients with insufficient tissue for a tension-free primary closure. Several prosthetic materials have been employed for this purpose, with varying results. We here review a long experience with the use of expanded polytetrafluoroethylene (ePTFE) patches in the open repair of large abdominal wall defects. METHODS: Demographic, operative, follow-up, and histologic data were recorded and analyzed for all patients in a surgical practice who were treated for large abdominal wall defects with open repair using ePTFE patches between November 1983 and March 1996. RESULTS: Ventral hernia repairs using an ePTFE patch were performed in 98 patients. In 48 (49%), the patient had already undergone at least one previous ventral hernia repair. Of the 98 operations, 78 were full-thickness repairs, 11 were Rives-Stoppa procedures, and 9 were onlay operations. Complications included 5 seromas, 3 fistulas related to removal of a previously implanted prosthesis, and 9 infections. In addition, 10 patients developed recurrent hernias not related to explantation of the patch because of infection or fistula. In 3 patients, infections were treated successfully without removal of the patch. There were no complications related to adhesions, erosion of the patch into the viscera, or bowel obstruction. Histologic studies of longterm ePTFE implants showed excellent fibrous tissue ingrowth and minimal foreign body response. CONCLUSIONS: Our long-term clinical experience indicates that prosthetic patches of ePTFE are safe and effective when used in the repair of large abdominal wall defects that cannot be closed primarily. Operative complications were within acceptable limits, as was the reherniation rate. PMID- 9989102 TI - Laparoscopic pelvic lymph node dissection in the staging of prostate cancer. AB - BACKGROUND: Men with localized prostate cancer who present with high risk features may benefit from determination of pelvic lymph node status by a laparoscopic lymph node dissection prior to definitive therapy. METHODS: One hundred eighty-nine men with a median age of 69 years (range 49-80) with T1-T3 prostate cancer had a laparoscopic pelvic lymph node dissection (LPLND) prior to definitive therapy (radiation or surgery). All patients had a negative bone scan and a computerized tomography of the pelvis prior to the LPLND. In addition, all patients also underwent a seminal vesicle biopsy (SVB) in order to determine the presence of T3c disease. Prostate-specific antigen (PSA) ranged from 1.6-190 ng/mL (median 11 ng/mL) and was > 10 ng/mL in 56.6%, Gleason score was > or = 7 in 46.7%, and 67.8% had clinical stage T2b-T3a. RESULTS: Of the 189 patients who underwent an LPLND, 22 (11.6%) had a positive dissection. Between 1 and 51 nodes (median 9) were removed per dissection. PSA, clinical stage, Gleason score and SVB results all significantly influenced node findings. Positive nodes were encountered in 26.5% of those with a PSA > 20 ng/mL (p = 0.0002), in 16.4% with stage T2b-T3a (p = 0.003), in 20% with Gleason scores 7-10 (p = 0.0006) and in 38% of men with a positive SVB (p < 0.0001). Logistic regression analysis with PSA, Gleason score, clinical stage and the results of the SVB demonstrated that a positive SVB was the most significant predictor of node positivity. The overall transfusion rate was 1% (2/189) and median hospital stay was one day. The complication rate for the LPLND was 9% (17/189). CONCLUSION: The LPLND is an effective and efficient means of detecting positive pelvic lymph nodes in patients with localized prostate cancer. It should be considered a necessary diagnostic modality in all appropriate patients who may be candidates for curative therapy. PMID- 9989103 TI - The impact of laparoscopic surgery in the management of adnexal masses. AB - The objective of this study is to evaluate the clinical aspects of laparoscopic management of adnexal masses. The feasibility of this approach has been demonstrated, but the safe and effective use of laparoscopy for this indication requires training, technical skills and experience on the part of the laparoscopist. If used appropriately, many patients will benefit from minimally invasive surgery. We compared clinical factors of patients having laparoscopy to those having laparotomy in a case-control study of 30 patients with adnexal masses. Oophorectomy or ovarian cystectomy was performed by laparoscopy for 20 women and by laparotomy for 10 women. Comparing the 2 groups, the most significant difference was the decrease in length of hospital stay in the laparoscopy group. There were no significant differences in operative time or intraoperative complications. Estimated blood loss was lower in the laparoscopy group, and no intraoperative complications occurred. No patient required conversion from laparoscopy to laparotomy. All patients had benign disease despite the inclusion of patients with risk factors for ovarian carcinoma. This study clearly demonstrates the clinical benefits of laparoscopic management of adnexal masses treated with oophorectomy or ovarian cystectomy. PMID- 9989104 TI - New medicine for the new millennium. PMID- 9989105 TI - [Bile acids and endotoxins: physico-chemical defense of the body]. AB - The toxic effects of endotoxin--the cell wall component of Gram negative intestinal bacteria--under experimental conditions can be induced only when they are administered parenterally. However, in naturally occurring enteroendotoxemic diseases (e.g. septic and various shocks, etc.), the endotoxin absorbs from the intestinal tract. The cause and mode of translocation was unknown. The generally used experimental shock models differ from natural diseases only in the mode by which endotoxin enters the blood circulation. If the common bile ducts of rats were chronically cannulated (bile deprived animals) perorally administered endotoxin was absorbed from the intestinal canal into blood circulation and provoked endotoxin shock. The translocation of endotoxins and consequent shock can be prevented by sodium deoxycholate or natural biles. The bile acids can split the endotoxin macromolecule (atoxic fragments). A similar destructive detergent action might will be a significant factor against potential infectious agents with lipoprotein outer structure (e.g. so-called "big" viruses). This defense mechanism of macrooganisms based on the detergent activity of bile acids is called as physico-chemical defense system. On the basis of this knowledge the bile acids might be used in the prevention and therapy of some clinical processes (e.g. hepatorenal syndrome; psoriasis). PMID- 9989106 TI - [The role of CT examination in the diagnosis and therapy of chronic thoracic empyema]. AB - Successful surgical treatment of chronic intrathoracic suppuration can, in the substantial majority of cases, be accomplished only by means of major surgery or a series of thoracic operations. If a solution to the chronic process cannot be provided by decortication of the lung, or should decortication not be possible due to the moribund condition of the patient, successful treatment can still be achieved through thoracic fenestration. 314 patients were treated for chronic suppuration in the thoracic cavity between 1st January 1987 and 31st December 1997. Of these, ten died, this representing a mortality rate of 3.1%. Seven of these ten patients suffered chronic suppuration. The total number of patients suffering chronic suppuration was 73 (23.2%). Of these 73 patients, in 31 cases treatment involving two or more surgical intervention procedures was performed. Three of the ten patients on whom open surgery was performed died, these having been referred to the department already in a moribund condition. It was decided that prolonged open surgery should be performed on three patients. CT examination enables the position of the empyema, the depth of the callus surrounding it, the position of drains and the relation between the visceral pleura and the pulmonary parenchyma and their demarcation to be determined prior to open surgery with greater precision than by any other diagnostic technique developed previously. CT examination has acquired a fundamental role, subsequent to partial resection or pneumonectomy, in the examination of the bronchial trunk and in the detection of fistulae. Following open surgery CT is also appropriate for the evaluation of the dimensions of the cavity, its form, the depth of granulation tissue, retraction of the bony thoracic structure and the condition of the bronchial stump. Where there is a precedent of tumours it can provide assistance in the detection of recurrence, lymph node conditions or metastasis. Complications arising subsequent to surgery (bronchial fistula, recurrent empyema, etc.) can thus be detected in due time. Prior to thoracoplasty or myoplasty the condition of the myocutaneous lobe twisted on a neurovascular spindle and sealing the cavity can be examined clearly by means of CT, as can the viability of the transposed skin and the muscle fascicle subsequently. PMID- 9989107 TI - [Effect of hemodialysis on QT dispersion in chronic uremia]. AB - Interlead variability of the QT interval in surface 12-lead ECG (i.e. QT dispersion) reflects regional differences in ventricular recovery time and it has been linked to the occurrence of malignant arrhythmias in different cardiac diseases. The purpose of the study was to assess the effect of hemodialysis on QT dispersion in chronic hemodialyzed patients. The data of 34 patients (Male/Female = 21/13, mean age 54 +/- 15 years) on chronic hemodialysis were studied. Simultaneous 12 lead ECGs were recorded pre- and post-hemodialysis in a standard setting. The QT intervals for each lead were measured manually by one observer. Each QT interval was corrected for patient's heart rate: QTc = QT/square route of RR (sec). The maximal QT interval changed from 449 +/- 43 to 469 +/- 41 ms (p < 0.01). The maximal QTc interval increased from 482 +/- 42 to 519 +/- 33 ms (p < 0.01). The QT dispersion changed rom 56 +/- 15 to 85 +/- 12 ms (p < 0.001), and the QTc interval from 62 +/- 18 to 95 +/- 17 ms (p < 0.001). During hemodialysis the serum potassium and phosphate decreased from 5.5 +/- 0.8 to 3.9 +/- 0.5 (p < 0.001), and from 2.3 +/- 0.5 to 1.6 +/- 0.4, respectively, whereas calcium level increased from 2.2 +/- 0.23 to 2.5 +/- 0.22 (p < 0.001). It can be concluded that the hemodialysis increased the inhomogeneity of regional ventricular repolarization. Measurement of QT and QTc dispersion by a cheap and simple bedside method could predict the increased myocardial inhomogeneity in dialyzed patients. PMID- 9989108 TI - [Epidemiologic study of regional inequalities]. AB - The technological achievements of the recent years and the need for more advanced control of the processes within the health sector have supported the geographical epidemiology to become a distinct branch of epidemiology. The combined application of the simple standardized rates, statistical tests and different corrected risk parameters is able to describe the health status for geographically defined, small populations. Several statistical processes have been elaborated to estimate the number of the false positive results and to evaluate the role of chance in predicting the observed geographical pattern. These data completed with the usual risk measures quantify the risk difference within a broader region and determine the actual risk levels for the investigated small areas. The routine data processing system operating as a part of the public health surveillance identifies the high risk areas (the clusters) and without leaving the framework of routine data handling investigates the association between basic exposure data and health risks producing additional data about the nature of the aggregation of health related events. All the spetially varying etiological factors (environmental effects, social status, traditions, regional features of the health sector etc.) are ready to elicit regional alterations in the health status. The aim of the geographical information system is to cover the consequences of the uneven distribution of these factors. Since these kind of etiological factors play significant role in the generation of the most important public health problems in Hungary, and it is known that the small area inequalities are profound for these health impairments, the more extensive application of geographical information systems is expected to improve the efficiency of the control for public health problems and the performance of preventive medicine. PMID- 9989109 TI - Headache in childhood. PMID- 9989110 TI - Atopic dermatitis. PMID- 9989112 TI - Index of suspicion. Case 2. Typhoid fever. PMID- 9989111 TI - Index of suspicion. Case 1. Hypersensitivity pneumonitis. PMID- 9989113 TI - What's new in perinatology. PMID- 9989114 TI - Consultation with the specialist. Thrombocytopenia. PMID- 9989115 TI - Psychiatric aspects of excellent end-of-life care. Ad Hoc Committee on End-of Life Care. The Academy of Psychosomatic Medicine. PMID- 9989116 TI - Depression in pediatric chronic illness. A diathesis-stress model. AB - Depression in pediatric chronic illness has been receiving increasing attention in recent years. Studies to date have typically focused on characteristics of illness as the major determinants of the development of depression, but characteristics of the child have received less attention. This review suggests that a diathesis-stress model can be a fruitful heuristic that would incorporate illness characteristics and attributes of the child and environmental effects in an overall framework to guide future research and treatment. PMID- 9989117 TI - Suicide risk assessment: a review of risk factors for suicide in 100 patients who made severe suicide attempts. Evaluation of suicide risk in a time of managed care. AB - A study of 100 patients who made a severe suicide attempt suggested that the managed care criteria often applied for approving admission to hospitals for potentially suicidal patients were not, in fact, predictive of features seen in patients who actually made such attempts. Severe anxiety, panic attacks, a depressed mood, a diagnosis of major affective disorder, recent loss of an interpersonal relationship, recent abuse of alcohol or illicit substances coupled with feelings of hopelessness, helplessness, worthlessness, global or partial insomnia, anhedonia, inability to maintain a job, and the recent onset of impulsive behavior were excellent predictors of suicidal behavior. The presence of a specific suicide plan or suicide note were not. Patients with managed care were overrepresented by 245% in the study. PMID- 9989118 TI - Competency evaluations on the consultation-liaison service. Some overt and covert aspects. AB - Competency assessments are a growing function of the consultation-liaison (C-L) psychiatrist. Such consultation requests often mask a variety of psychosocial issues that are a source of frustration to the referring physician responding to the pressures of the changing health care delivery system in the acute care setting. This study identifies the issues and the outcome of psychiatric consultation in these patients. The implications of this burgeoning role for the C-L psychiatrist are also explored. PMID- 9989119 TI - Attachment and interpersonal communication in somatization. AB - The authors review the research on childhood antecedents and personality contributions to the somatoform disorders, as well as research on social influences during adulthood. Based on these data, the authors hypothesize that somatizing patients display anxious attachment behavior that derives from childhood experiences with caregivers. Early exposure to illness increases the likelihood that distress will be manifested somatically. When under stress as adults, somatizers use physical complaints to elicit care. Somatizers' interpersonal interactions with others, including physicians, ultimately lead to rejection that reinforces the somatizer's belief that he or she will be abandoned. Modification of physicians' responses to these patients may improve treatment outcomes. PMID- 9989120 TI - The Millon Behavioral Health Inventory Life Threat Reactivity Scale as a predictor of mortality in patients awaiting heart transplantation. AB - This study examined the Millon Behavioral Health Inventory Life Threat Reactivity Scale (LTRS) as a predictor of mortality in patients awaiting heart transplantation. The one-year mortality while awaiting cardiac transplantation was more than double for the high-risk group based on the LTRS scores. The high risk group had a 42% mortality rate versus an 18% mortality rate in the low-risk group. Mortality for those patients that received transplants was similar for both groups. A review of the medical literature regarding the role of personality traits in cardiac mortality and the findings of this study are discussed. PMID- 9989121 TI - Panic disorder patients and their medical care. AB - The goal of the study was to examine the functional status and medical care of general medical outpatients with panic disorder. One hundred patients completed self-report questionnaires and a diagnostic interview for panic disorder. They were compared with a random sample of patients without panic disorder. Medical morbidity was assessed from the medical record, and the patients' clinic physicians completed a questionnaire about them. The prevalence of current (1 month) panic disorder was 6.7%-8.3%. The panic disorder patients had fewer serious medical diagnoses, but more medical utilization and more role impairment than the comparison group. The clinic physicians rated the panic patients as more anxious, more depressed, more hypochondriacal, and more difficult to care for. Sixty-one percent of the panic disorder patients recalled receiving an anxiety disorder diagnosis. These findings add to a growing body of evidence that panic disorder imposes a significant burden on those with this illness and that it is a seriously underdiagnosed condition in primary care practice. PMID- 9989122 TI - Psychiatric disorders in patients with fibromyalgia. A multicenter investigation. AB - The authors conducted an investigation in four tertiary-care centers to determine if psychiatric comorbidity and psychological variables were predictive of functional impairment in patients with fibromyalgia syndrome (FMS). Seventy-three individuals were administered the Structured Clinical Interview for DSM-III-R, the Rand 36-item Health Survey (SF-36), and multiple self-report measures. The patients with FMS were found to have a high lifetime and current prevalence of major depression and panic disorder. The most common disorders were major depression (lifetime [L] = 68%, current [C] = 22%); dysthymia (10% [C only]); panic disorder (L = 16%, C = 7%); and simple phobia (L = 16%, C = 12%). The self report scales revealed significant elevations in depression, anxiety, neuroticism, and hypochondriasis. Functional impairment on all measures of the SF 36 was severe (e.g., physical functioning = 45.5 and role limitations due to physical problems = 20.0). Stepwise multiple-regression analysis revealed that current anxiety was the only variable that predicted a significant proportion of the variance (29%) in SF-36 physical functioning. Thus, in this multicenter study, the persons with FMS exhibited marked functional impairment, high levels of some lifetime and current psychiatric disorders, and significant current psychological distress. Current anxiety level appears to be an important correlate of functional impairment in individuals with FMS. PMID- 9989123 TI - Screening for anxiety and depression in women with breast cancer. Psychiatry and medical oncology gear up for managed care. AB - In this study, 275 women with breast cancer attending ambulatory breast cancer clinics in two sites were evaluated for psychological distress by using three self-report instruments: a visual analogue scale for psychological distress, the Hospital Anxiety and Depression Scale, and the Brief Symptom Inventory. Results suggest that significant psychological distress exists in ambulatory women with breast cancer; all three instruments effectively measured that level of distress. Implications for the use of these instruments in educating oncological staff members, documenting need for psychiatric services in a period of capitation, and providing quality assurance evaluations of psychiatric services are discussed. PMID- 9989124 TI - Major depression and its response to sertraline in primary care vs. psychiatric office practice patients. Results of an open-label trial in Argentina. AB - Great strides have been achieved in recent years in the detection and treatment of major depressive disorder (MDD) in primary care settings. Little is known about the types or patients with MDD seen in primary care as compared with those seen in psychiatric office practice. Few studies have compared clinical outcomes after treatment with antidepressants in these two settings. In Argentina, the authors conducted an open-label treatment study of MDD patients in primary care (n = 469) and psychiatric office practice (n = 299). The patients were compared on baseline sociodemographic and clinical variables. These same patients were treated with sertraline 50-100 mg per day for 8 weeks. At baseline, the patients in psychiatric office practice were younger, more likely to abuse alcohol, less likely to have comorbid medical disorders, and more likely to have failed a prior treatment for depression during the current episode. The two groups did not differ significantly on depression severity or in depressive symptom profile on the Hamilton Depression Rating Scale (Ham-D). After 8 weeks of treatment, mean Ham-D scores were reduced comparably in both groups, from about 25 to about 10. Rates of adverse events were 14%-29%, depending on the follow-up interval. Adherence with treatment was high in both groups (over 95%). The patients in primary care and psychiatry office practice are similar in several ways. Significant reductions in depressive symptoms are possible in both settings, in large numbers of patients, by using doses of sertraline in the 50-100 mg range. PMID- 9989125 TI - Induction of a schizophreniform disorder by a spinal cord stimulator. PMID- 9989126 TI - Near-fatal skin picking from delusional body dysmorphic disorder responsive to fluvoxamine. PMID- 9989127 TI - PTSD and automatic implantable cardioverter defibrillators. PMID- 9989128 TI - Anorexia nervosa in a 38-year-old woman 2 years after gastric bypass surgery. PMID- 9989129 TI - PTSD in women with breast cancer. PMID- 9989130 TI - [Commentary on the 6th Report of the American National Committee on Prevention, Detection, Evaluation and Treatment of High Blood Pressure]. AB - Systemic hypertension is present world-wide and it is a leading cause of cardiovascular morbidity and mortality. A great number of different drugs have been used in the treatment. Many other drugs are being developed, but evidence upon their effect on morbidity and mortality is not always present. In this setting, the sixth report of the National Committee on Detection, Evaluation, and Treatment of High Bloos Pressuere, review the safety and efficacy of therapies in hypertension. In the absence of counter-indications diuretics and beta-blockers should be used as first-line agents. Treatment must be based, not only on the level of blood pressure. Risk factors, target organ disease, and other comorbid diseases are considered. Not all the recommendations are solidly based. PMID- 9989131 TI - [The performance of coronary angioplasties at centers without cardiac surgery. The recommendations of the Sociedad Espanola de Cardiologia]. AB - During the early years of coronary interventions a rigorous on-site surgical stand-by was mandatory. The increased experience in coronary angioplasty both on total number of procedures and the experience gained by each operator, together with the technical improvements, namely since the introduction of stents has induced an evolution in the stand-by strategy, with new concepts such as "next available operating room" or coronary interventions "without on site" surgical facilities, are gaining widespread acceptance. With the aim of defining the requirements to perform coronary interventions at hospitals without coronary surgery, the following aspects are reviewed: a) complications following coronary angioplasty that require coronary surgery; b) the current status of coronary angioplasty without surgical stand-by in different countries. All this information allows us to advance some recommendations concerning the performance of coronary interventions at hospitals without on-site cardiac surgery. Different issues including hospital characteristics, operator and cardiac catheterization laboratory requirements, as well as lesion characteristics and the type of informed consent, should be taken into account. PMID- 9989132 TI - [The National Registry of Cardiac Tumors (the 1996-1997 report)]. AB - We presented the first report of the national database of heart tumors. We described the origin, development and goals reached during the years 1996 and 1997, the way the data was collected and the form used. The cases collected until 31st of December of 1997 include 165 tumors in 155 patients distributed all around the country. Age and gender distribution, way of diagnosis, morphologic classification, treatment and follow-up of this pathology is reported. PMID- 9989133 TI - [The evolution of severe postvalvuloplasty mitral insufficiency]. AB - Percutaneous mitral valvuloplasty has become the technique of choice for mitral stenosis with favorable anatomic features. However, mitral regurgitation is an important complication of this technique that has not reduced with Inoue technique. This study reports the clinical and echocardiographic follow-up (28 +/ 20 months) of 20 patients who developed severe mitral regurgitation after percutaneous mitral valvuloplasty with Inoue technique. The patients were divided into two groups on the basis of the need for mitral valve replacement during follow-up. We analyzed variables before and after percutaneous mitral valvuloplasty using univariate analysis. Multivariate analysis was performed to identify variables as independent predictors of the need for mitral valve replacement. Ten patients needed mitral valve replacement during follow-up. Multivariate analysis showed that suboptimal result of percutaneous mitral valvuloplasty (MVA < 1.5 cm2) was the only independent predictor of the need of mitral valve replacement. We concluded that the need for MVR in patients who develop severe mitral regurgitation after percutaneous mitral valvuloplasty was related to suboptimal result of procedure. PMID- 9989134 TI - [Improvement in fibrinolytic function following anticoagulant treatment in chronic rheumatic atrial fibrillation]. AB - INTRODUCTION AND OBJECTIVES: Patients with rheumatic atrial fibrillation are considered at high risk of systemic embolism and require oral anticoagulation. Fibrinolytic function has been little studied. We evaluated fibrinolytic activation markers before starting anticoagulation, at 1 and 6 months following the introduction of oral anticoagulation therapy. We analyzed the relationship with left atrial diameter and mitral area. METHODS: Tissue plasminogen activator (tPA), its inhibitor (PAI-1), plasmin-antiplasmin complexes (PAP) and D-dimer were measured in 13 patients with rheumatic atrial fibrillation. Basal levels were compared with those found in plasma of 20 healthy subjects matched by sex and age. Transthoracic echocardiography was made. RESULTS: A significant increase for PAI-1 and D-dimer levels were detected in patients with atrial fibrillation group (p < 0.05), with no differences in tPA and PAP concentrations. Significant correlation between left atrial diameter and basal t-PA levels was found. Levels of t-PA, PAI-1 and D-dimer decreased significantly under anticoagulation therapy, whereas PAP levels were significantly increased. CONCLUSIONS: Patients with rheumatic atrial fibrillation show a relative hypofibrinolytic state due to elevated PAI-1 levels with no increase in PAP concentration. At six months of anticoagulation therapy, an improvement of fibrinolytic function markers was observed. This is consistent with the prophylactic effect of oral anticoagulants therapy against thromboembolic risk. PMID- 9989135 TI - [The measurement of jet width at its origin in assessing mitral prosthetic regurgitation. The effect of the spatial disposition of the jet]. AB - INTRODUCTION AND OBJECTIVES: The study was performed to test the influence of the jet spatial disposition on the correlation degree between the measurement of the jet width at its origin and the severity of mitral prosthetic regurgitation by transesophageal Doppler color flow imaging. MATERIAL AND METHODS: In 165 patients with mitral valve prosthesis which were submitted for transesophageal echocardiography examination due to suspected prosthetic dysfunction, we studied 126 with pathological mitral regurgitation. On these patients, studies of jet spatial disposition, maximum width in its origin and severity quantification by means of maximum regurgitation area were performed. RESULTS: For the free jet group of patients (90), jet width at its origin correlated with maximal regurgitation area (r = 0.75); whereas for the wall jet group (36), the correlation degree was 0.59. We observed a relationship (p < 0.05) between severe mitral regurgitation assessed by maximal regurgitant jet size and jet width > or = 5 mm in both groups: the sensitivity and specificity of 72.7% and 95% respectively for free jets, and 70.7% and 64.4% for wall jets. CONCLUSIONS: The correlation between the area measurement and the width in its origin is better for free jets than for wall jets. A statistically significant relationship between the presence of severe mitral regurgitation and width in its origin > or = 5 mm could be observed, independently of the jet spatial disposition. PMID- 9989136 TI - [The characteristics proper of the cardiac cycle phases of the right ventricle]. AB - AIMS: The purpose of our study was to define at physiological conditions, the existence or not of an isovolumic relaxation phase in the right ventricle and its ejective phase properties. MATERIAL AND METHODS: Right and left ventricular pressures, pulmonary and aortic pressures, pulmonary flow and ventricular diameters by sonomicrometry were measured in nine anesthetized sheep. The first ventricular pressure derivative, ventricular volumes, and the right and left pressure-volume loops, were calculated "off line". An abrupt preload reduction was generated by a posterior vena caval occlusion. RESULTS: Right ventricle showed an ejection phase which can be subdivided in two phases (early and late). The end of the ejection phase was established by the temporal coincidence of the zero pulmonary flow, the minimum systolic value of the right ventricular volume and a right ventricular pressure of 0-4 mmHg. The time between the beginning of the ejection phase and: a) the end of systole; b) the negative peak of the first derivative of ventricular pressure and c) the end of ejection, were different for the right ventricle (67 +/- 15 ms, 274 +/- 30 ms, 412 +/- 33 ms, respectively), meanwhile the left ventricle showed the following values: 204 +/- 33 ms, 262 +/- 23 ms, 266 +/- 24 ms, respectively. CONCLUSIONS: Right ventricle exhibits a long lasting ejection phase which can be subdivided in two phases, spreading at the beginning of the next filling phase. This fact allows us to affirm that right ventricle does not show an isovolumic relaxation phase in comparison to left ventricle. PMID- 9989137 TI - [Hemodynamic differences between the right and left ventricles]. PMID- 9989138 TI - [Ventricular geometry and heart failure]. AB - In the last years there has been an appreciation of the importance of left ventricular geometry. After a period, in the sixties and seventies, that the interest was focused on cardiac physiology and the left ventricular geometry role about this subject, new studies are available on clinical significance of normal or distorted left ventricular shape. New assessment methods of ventricular geometry have been described. The use of simple measurements to assess ventricular geometry has allowed to know the clinical value of the shape distortion in patients with heart failure. The suspicion that left ventricular shape change to sphericity has prognosis value, has raised the interest about this subject. Whether distortion of left ventricular shape is an even better parameter than cardiac function indices normally used is under consideration. Moreover, new surgical therapies have been developed in an attempt to improve the ventricular geometry and to get better clinical prognosis in patients with heart failure. PMID- 9989139 TI - [Severe myocardial restriction secondary to massive calcification of the left ventricle]. PMID- 9989140 TI - [Multiple coronary aneurysms in a young man. A diagnostic approach via different technics]. AB - Coronary aneurysms are uncommon. The most frequent etiologies are atherosclerotic and congenital, although there are several other rare causes. Myocardial infarction and sudden death may be the initial manifestations which are usually a consequence of aneurysm complications such as rupture or distal embolization. Although coronariography is the gold standard diagnostic technique, coronary aneurysm may also be detected by non-invasive methods such as ultrasonography and nuclear magnetic resonance. We report the case of a young male with hypercholesterolemia who presented cardiac arrest as the first clinical manifestation. Ultrasonography and MRI revealed the presence of multiple coronary aneurysm. This case illustrates the usefulness of non-invasive techniques for the diagnosis of coronary aneurysm. PMID- 9989141 TI - [A right atrial thrombus in transit: its echocardiographic diagnosis 72 hours before a pulmonary embolism]. AB - We report a case of a 72-year-old woman with coronary artery disease in whom a thrombus in transit in the right atrium was diagnosed accidentally. After 72 hours of treatment with intravenous anticoagulants she developed a pulmonary thromboembolism resolved with systemic fibrinolysis. This is a rare case in which such a diagnosis preceded an embolic event. This fact raises the controversy about the best therapeutic management of this unusual form of thromboembolic illness. PMID- 9989142 TI - [Atherosclerotic coronary ectasia or a lymphomucocutaneous syndrome in an adult (Kawasaki's disease)?]. AB - We report the case of a 42-year-old man, who was admitted to hospital with an inferior myocardial infarction. He was treated with tissue plasminogen activator without complications in the acute phase. The stress testing performed before discharge showed residual myocardial ischemia. A catheterization study was indicated. The coronary angiogram demonstrated diffuse three vessel coronary artery aneurysmal disease. Two years before the patient had an aneurysm of the right iliac artery being operated on. The differential diagnosis of adult aneurysmal coronary disease is discussed with emphasis on Kawasaki's disease and atherosclerotic coronary artery ectasia. PMID- 9989143 TI - [Valve repair in tricuspid endocarditis in the drug addict. Apropos a case]. AB - Valve replacement, valvulectomy and valve repair are the alternatives for the surgical treatment of intractable tricuspid valve endocarditis. We present the case of a 24-year-old, HIV-positive Caucasian female, intravenous drug addict, with intractable tricuspid valve endocarditis, that was successfully treated with tricuspid valve repair. Advantages and major drawbacks of the different techniques are discussed and the appropriate literature is reviewed. PMID- 9989144 TI - [The surgical treatment of critical aortic stenosis in a child by the Ross-Konno technic]. AB - A twenty-nine-day old male infant suffering from critical aortic stenosis underwent aortic valvotomy by cardiopulmonary bypass. At three years of age the aortic stenosis recurred and the child underwent a balloon aortic valvuloplasty, but developed severe aortic insufficiency after the procedure. The critical condition of the patient made aortic valve replacement mandatory. The surgical technique consisted of aortoventriculoplasty with infundibular and valve pulmonary autograft for substituting the aortic root (Ross-Konno technique). As for as we know this is the first report on the Ross-Konno procedure in Spanish journals. PMID- 9989145 TI - [Endothelium and sickle cell anemia, or how an amino acid mutation disturbs blood circulation]. PMID- 9989146 TI - [Jean Pecquet (1622-1674) and his cistern]. PMID- 9989147 TI - [Eutocic delivery ]. AB - Delivery is uncomplicated in 60 to 75% of cases. Movement through the pelvic pathway requires precise foetal mobility in relation to the pelvis, since the head must pass using a double rotation: 120 degrees deflection around the symphysis pubis and 45 degrees to 135 degrees rotation around the pelvic cavity, according to the presentation. This mechanism, imposed by the adaptation of the form of the pelvis to the upright position, is possible cue to an apparent reduction in volume of the foetal head by its molding and its flexion. This accommodation is favoured by the maturity of the foetal nervous system, the maturity of the uterus, and by the type of presentation. Anterior presentation (anterior left occipito-iliac), more common in multiparas, is usually safer than posterior presentation (posterior right occipito-iliac). more often seen in primiparas. PMID- 9989148 TI - [Instrumental and manual maneuvers during delivery]. AB - Delivery through the maternal genital tract can be assisted or performed using specific instruments. In France, these techniques are used in 15% of deliveries. The three instruments used are the forceps, the vacuum extractor and the spatula. Manual manoeuvres are essentially used in breech presentation. These are mainly partial and total breech extractions with their many variations. The version consisting of external manoeuvering precedes delivery. In cephalic presentations, the only possible manual manoeuvre is manual rotation of the foetal head. PMID- 9989149 TI - [Cervical ripening and labor induction]. AB - To induce labour successfully, a good cervical status and favorable obstetrical conditions are necessary. If these conditions are not present, cervical ripening must take place before induction of labour. Cervical ripening is only justified when a pathology (maternal or foetal) indicates termination of pregnancy. Intracervical or intravaginal administration of prostaglandin E2 is actually the standard for cervical ripening. PMID- 9989150 TI - [Severe maternal and fetal situations during delivery]. AB - If pregnancy is very frequently normal, severe complications can appear for fetus, mother or both. The etiologies are various but preeclampsia and its complications remain one of the leading causes. The management is discussed according to the etiology and the severity of the disease and also the level of maternity and neonatal unit which can accept the newborn. However, all situation is a case apart and any decision will not be taken without concertation between obstetricians and neonatologists. In France, a regionalization policy is taking place to improve the maternal and neonatanal management. PMID- 9989151 TI - [Postpartum hemorrhage]. AB - Postpartum haemorrhage, the second cause of maternal mortality in France, is an obstetric and anaesthetic emergency. Yet, it often seems avoidable as most patients at risk can be identified before or during labour. In this respect, obstetrical conduct regarding delivery is essential; it makes it possible to foresee the necessary preventive and curative measures. Once haemorrhage has begun, any delay or hesitation in assuming multidisciplinary responsibility is potentially detrimental as it may lead to coagulopathy complications. Whenever possible, arterial embolisation presents an enormous progress in noninvasive conservative treatment, especially after vaginal delivery. Stepwise uterine devascularisation seems to be a promising surgical option as it can be used under all conditions, preserves maternal fertility, and is clearly effective. PMID- 9989152 TI - [Pelvic and perineal sequelae of delivery]. AB - Vaginal delivery especially with dystocia, may result in relaxation or disruption of fascial and ligamentous supports of pelvic organs. The relationship between first childbirth and obstetric trauma is strong but additional pregnancies and deliveries are aggravating factors as well as ageing and hormonal effects of the menopause. These anatomic changes are contributing to the development of stress urinary incontinence, anal incontinence and genital prolapse. Preventing obstetric trauma needs changes in current obstetric practice: reduction in the episiotomy rate, use of vacuum extractor in preference to forceps. General practitioners can help at the time of postnatal control by making a full clinical evaluation of pelvic floor damage, referring women for further investigation and asking them about postnatal sexual difficulties. Postpartum perineal physiotherapy is indicated for women at risk: pelvic floor congenital weakness instrumental delivery, postpartum urinary and/or anal incontinence. PMID- 9989153 TI - [Anesthesia and delivery]. AB - Close collaboration of an informed anaesthetist with the obstetrician, and respect of the security protocols in every anaesthesia must guarantee the well being of pregnant women. The development of loco-regional anaesthesia for use in labour analgesia and caesarean section has reduced the indications and the mortality related to general anaesthesia. In the last 30 years, analgesia and control of loco-regional anaesthesia effects have been greatly improved. Loco regional anaesthesia protocols are now safe for the mother and various. Epidural anaesthesia using low concentrations of local anaesthetics allows parturient ambulation. Intrathecal anaesthesia, with combined spinal-epidural technique, is mostly used for caesarean-section and for the early and late labour. PMID- 9989154 TI - [Maternal morbidity and mortality related to delivery]. AB - Maternal mortality related to delivery is theoretically easy to quantify and constitutes a good indication of the security and quality of obstetrical care. Although its incidence continues to decrease in France, it is still higher than in several of our European neighbors. Hence management of pregnancy is still deficient in this country. Fifty per cent of deaths occur at the time of delivery or immediately thereafter, and case analysis shows that the majority of these deaths, particularly those due to haemorrhage, could have been avoided by earlier diagnosis or better adapted treatment. PMID- 9989155 TI - [Clinical practice]. PMID- 9989156 TI - [Cystic fibrosis]. PMID- 9989157 TI - [Bladder tumors]. PMID- 9989158 TI - [Dementia syndrome]. PMID- 9989159 TI - [Hemorrhagic shock]. PMID- 9989160 TI - [Antidepressive agents]. PMID- 9989161 TI - [Cancer of the testicle]. PMID- 9989162 TI - [Vomiting in infants]. PMID- 9989163 TI - [Iatrogenic pathology--a current forensic medical problem]. AB - Profound studies of iatrogenesis from a medical and legal viewpoint are an important task. New medicolegal terms and notions and a classification of iatrogenic conditions are offered for discussion. PMID- 9989164 TI - [The use of impedance plethysmography in the forensic medical diagnosis of the time of death]. AB - Diagnosis of the time of death (DTD) is a pressing problem of forensic medicine. For defining the criteria of DTD by impedance plethysmography, electric conductivity of tissues was studied in 45 corpses of male subjects aged 18-44 years who died from craniocerebral injuries. Autolytic changes were characterized by a wave-like pattern, with periods of stability replaced by necrobiotic processes. This allows recording residual activity of surviving cells and tissues in a corpse during the early postmortem period. Based on these data, a model of postmortem changes in tissues can be created for DTD. PMID- 9989165 TI - [The evaluation of the mechanism of intracerebral parenchymatous hemorrhages under different types of dynamic loads on the brain]. AB - Possible mechanisms of intracerebral hemorrhages in craniocerebral injuries are analyzed. Comprehensive pathomorphological, topographoanatomical, and expert studies helped the authors disclose the biophysical processes in the cranial cavity. These processes act as internal damaging factors and underlie the formation of intracerebral hemorrhages. The authors discuss the role of tension and cutting deformations of cerebral structures in development of cerebral hemorrhages and the significance of topographic and anatomic features of the base of the skull and discrete cavitation in cerebral tissue occurring in total deformations of the skull. Relationship between morphology and topography of intracerebral hemorrhages and the site of impact and direction of the damaging force is considered. PMID- 9989166 TI - [The histological study of puncture-stab wounds of the skin for establishing the characteristics of the design of the knife blade]. AB - Histologic studies can help disclose the design of the knife blade by which a cut wound was inflicted. For analysis, thick (25-30 microns) sections are made, parallel to skin surface near the ends of a cut wound. The ends of the wound formed by the blade edge and back are different, and some specific features of the blade back, primarily its thickness, can be distinguished. When the suspected knife is available, a valid conclusion can be made by comparing experimental wounds inflicted by this knife with the studied wounds. PMID- 9989167 TI - [The characteristics of the morphological changes to the parenchymatous organs in persons who used street narcotics]. AB - Morphologic signs of narcomania in subjects using primitively prepared narcotics from opium-containing raw material are described. Sites of injections and inflammatory reactions in the parenchymatous organs are described. Special attention is paid to productive hypersensitive inflammation, which can serve as a sign confirming narcomania in subjects using poorly purified narcotic mixture. The authors classify the granulomas in such patients as toxic allergic granulomatosis. PMID- 9989168 TI - [Establishing the presence of blood in stains for material evidence by using the luminescent blood test]. AB - Two methods for objective persuasive identification of blood stains on pieces of material evidence are offered. These methods are 1000 times more sensitive than other methods used in forensic medical practice. Computer processing of the results permits calculating the content of hemoglobin derivatives in the examined material in amounts as low as 5-100 ng/100 microliters extraction. Using these methods, it is possible to prove the presence of blood by rapid analysis directly at the site of the crime in washed traces and in traces formed long ago. PMID- 9989169 TI - [The determination of mixed stains of blood and cells on the knife blade in the case of the wounding of several victims]. AB - Discusses the probability of disclosing the fact of wounding several subjects with the same knife on the basis of analysis of two cases. A complex method for analysis of traces on the knife blade consisted in assessment of the group and sex appurtenance of blood and detection of cells including the diagnosis of their sex, group, and organ and tissue origin. PMID- 9989170 TI - [The forensic chemical study of psilocybine-containing fungi]. AB - A method for isolating the main components (psilocybin and psilocine) from Psilocybe semilanceata mushrooms, their identification and measurement by thin layer and gas-liquid chromatography, chromatographic mass-spectrometry, and inverse-phase high-performance liquid chromatography is developed. PMID- 9989171 TI - [The isolation and determination of different narcotic and drug substances after the acid hydrolysis of biological material. (1)]. AB - A modified method for isolation of toxicologically significant substances after acid hydrolysis of biological material is proposed. Drugs and narcotics of different groups were identified, which are not disintegrated after acid hydrolysis of biological material and are isolated in high amounts. PMID- 9989172 TI - [The determination of 4-nitrophenols in objects of biological origin]. AB - The possibility of isolating 4-nitrophenols from objects of biological origin by acetic anhydride is investigated. Extracts from biological material were purified by extraction followed by silica gel thin layer chromatography. A method for identification and measurement of phenol 4-nitro derivatives in extracts of human cadaveric liver and blood is developed. PMID- 9989173 TI - [The comparative characteristics of methods for determining technological liquids in clinical toxicology]. AB - Methods for preparing biological samples and of gas chromatographic analysis of toxic technological liquids are compared. The sensitivity and reproducibility of the results of measuring these substances in the vapor-gas phase and during direct introduction of biological samples in the column are assessed. The possibility of direct introduction of a sample for qualitative and quantitative assessment of several volatile solvents simultaneously present in the samples is demonstrated. PMID- 9989174 TI - [The determination of the posture of the victim at the moment of the infliction of a gunshot wound]. PMID- 9989175 TI - [A fall from a great height onto tree branches]. PMID- 9989176 TI - [A case of Dertil poisoning]. PMID- 9989177 TI - [The age-related morphology of the male genitalia]. PMID- 9989178 TI - [Francisk Keresturi--one of the first forensic physicians of Moscow]. PMID- 9989179 TI - Medicare+Choice: reality sets in. PMID- 9989180 TI - Unethical duels between departing physicians and their medical groups. PMID- 9989181 TI - Perils of ignoring the family. PMID- 9989182 TI - Proctitis cystica profunda--an unusual rectal mass with varied etio-pathogenesis. PMID- 9989183 TI - Acute lung injury after massive household endotoxin exposure. AB - Household exposures may result in a variety of respiratory illnesses. Most of these inhalation injuries are benign and self-limited. However, an acute injury that results in exacerbation of asthma or chronic fibrosing processes may be life threatening. We report the case of a patient who suffered a massive household dust exposure when the bag of his upright vacuum cleaner exploded. Inhalation of the dust resulted in respiratory distress characterized by non-cardiogenic pulmonary edema. We believe this is the first report of acute respiratory distress syndrome (ARDS) as a result of endotoxin exposure from the inhalation of household dust. PMID- 9989184 TI - Assistive technology in Tennessee. PMID- 9989185 TI - A case of Streptococcus bovis bacteremia and endocarditis. PMID- 9989186 TI - Colonoscopy in rural family practice--response. PMID- 9989187 TI - [A good Scientific Practice]. PMID- 9989188 TI - [Prevention of ischemic heart disease--the absolute risk]. PMID- 9989189 TI - [Can preventive measures reduce the incidence of ankle sprains? Results of a Cochrane meta-analysis]. PMID- 9989190 TI - [Familial occurrence of chronic tension headache]. AB - Chronic tension-type headache occurs in 3% of the Danish population. the aetiology remains an enigma, even though it is one of the most frequent illnesses with chronic pain. A family study indicates the importance of genetic factors. Compared with the general population, first degree relatives (parents, siblings and children) of probands with chronic tension-type headache have a three-fold significantly increased risk of chronic tension-type headache, while spouses had no increased risk. Complex segregation analysis indicates multifactorial inheritance. Thus, a combination of genetic and environmental factors causes chronic tension-type headache. PMID- 9989191 TI - [Cerebral dysfunction occurring after years of latency]. AB - A number of basically very different factors may affect the central nervous system and result in progressive loss of mental or physical functions immediately or after a latent period of decades, possibly due to the initial factor being combined with an additive effect of aging. Intoxication with 1-methyl-4-phenyl 1,2,3,6-tetrahydropyridine (MPTP) induces degeneration of the basal ganglia. Various vira e.g. poliovirus and retrovirus may give rise to acute or late effects after several years. The Concentration Camp Syndrome may lead to a dementing illness with a latency of 10-30 years. Signs of progressive degenerative CNS disease should give rise to considerations of possible provoking factors earlier in the patient's life history. PMID- 9989192 TI - [Intra-articular glucocorticoid injections in joint diseases]. AB - Intra-articular glucocorticosteroid injections are widely used in mono- or oligoarticular flares of patients with rheumatoid arthritis and other aseptic inflammatory joint diseases, as well as in osteoarthritis. Rapid and pronounced, but usually temporary, suppression of local joint inflammation may be achieved with only minor systemic effect. In osteoarthritis the effect is brief and transient. Triamcinolone hexacetonide provides the longest clinical effect, but since this drug may cause local tissue necrosis when injected outside a synovial cavity it should be used only by experienced clinicians. The risk of glucocorticoid-induced cartilage damage is discussed. The risk is probably less than that of untreated joint inflammation. Nevertheless, it is recommended that injections into the same joint are limited, for instance to one injection every six weeks and no more than three or four in one year. Furthermore, indications and contraindications should be carefully considered prior to each injection. Intra-articular glucocorticoid therapy may be of considerable clinical value in the management of aseptic arthritis, if administered on correct indications using a correct technique. PMID- 9989193 TI - [Single-chamber atrial pacing is better than single chamber ventricular pacing in patients with sick sinus syndrome. Results of long-term follow up in a prospective randomized study]. AB - In a study of 225 patients with sick sinus syndrome randomized to single chamber atrial pacing (n = 110) or ventricular pacing (n = 115), atrial pacing was associated with less atrial fibrillation and thromboembolism after 3.3 years follow-up. To determine whether this beneficial effect of atrial pacing is maintained at long-term, follow-up was extended. Follow-up visits were at 3 months, 12 months, and then once every year, and included physical examination, ECG, and pacemaker check-up. After 5.5 years follow-up, all-cause mortality, cardiovascular deaths, atrial fibrillation, thromboembolism, and heart failure were significantly less in the atrial group. AV block occurred in four patients in the atrial group. The beneficial effect of atrial pacing observed previously is enhanced substantially after extended follow-up. Patients with sick sinus syndrome should be treated with an atrial pacing system. PMID- 9989194 TI - [The effect of transdermal nicotine patches in smoking cessation. A randomized trial in pharmacy customers in Denmark]. AB - The aim of the study was to examine the effect of 24-hour nicotine patches in smoking cessation among over-the-counter customers in Denmark based on a randomized, double-blind, placebo-controlled trial. Participants were consecutive customers to whom nicotine patches were offered free of charge and as the only treatment. Forty-two pharmacies in the areas of Aarhus and Copenhagen in Denmark participated in the trial, and 522 customers who smoked 10 or more cigarettes per day were randomized to either nicotine or placebo patches from January to March 1994. Twenty-four-hour patches were offered for a three-month period. Those smoking 20 or more cigarettes per day started on 21 mg/day patches. Customers who smoked less started on 14 mg/day patches and all the participants were gradually reduced to 7 mg/day patches during the study period. Smoking behaviour and compliance were recorded by means of self-administered question-naires and telephone interviews. Smoking status was recorded following each four-week treatment period, and 26 weeks after inclusion. There was a significant increase in smoking cessations rates, but only among smokers who started on 21 mg/day patches after eight weeks of follow-up. No significant differences in smoking cessation rates were seen among smokers who started with the low dose nicotine or placebo patches. PMID- 9989195 TI - [Pancreaticoduodenectomy--Whipple's operation--for periampullary cancer in patients over 70 years of age]. AB - Thirty-four consecutive patients with an age over 70 years with periampullary cancer were operated on with pancreaticoduodenectomy (Whipple's procedure). The operative procedure included an extensive dissection of the regional connective tissue and lymph nodes including the retroperitoneum. Postoperative medical complications occurred in 24% and surgical complications in 53% of the patients. Four patients (12%) died in the postoperative period (within 30 days), and three patients (9%) died later in the postoperative course. The cumulative and age corrected five-year survival for the remaining patients was 26%. Fifteen patients died from recurrence, and seven patients from other causes. In patients with a non-radical operation the median survival was 1 1/2 years, which is longer than could be expected with other palliative procedures. Apart from a moderately increased postoperative mortality the results were similar to those reported for younger patients. In conclusion, pancreaticoduodenectomy may be considered in patients with an age over 70 years with operable periampullary cancer. A five year survival rate of 20-35% can be obtained. Palliative resection is indicated in patients in good general condition, as resection gives the best palliation and longer survival than other palliative methods. PMID- 9989196 TI - [Alcohol-related admissions to a psychiatric departments]. AB - The purpose of this investigation was to find out the number of hospitalizations of alcoholics in a department of psychiatry throughout one year. Further, some characteristics of the patients were noted. The information was gathered from case sheets of patients who had been hospitalized in the period 01.10.96 30.09.97, and who were given a F10.x diagnosis from the ICD-10 system. The investigation showed that about one fifth of the patients hospitalized in the department were alcoholics. Fore more than half of these patients, the reason for hospitalization was for treatment that according to guidelines should have been given in an outpatient setting. The study confirms that there is a need for facilities for inpatient treatment for alcoholics, and that offering outpatient detoxification is not sufficient. PMID- 9989197 TI - [Bowing fracture of the ulna with concomitant dislocation of the distal radioulnar joint]. AB - This work presents the first case of bowing fracture of the ulna associated with dislocation of the distal radioulnar joint. Etiology, radiographs and treatment are described and discussed. Bowing fractures are frequently missed on primary examination, mainly due to their rarity and the fact that the primary examination in the accident and emergency department is undertaken by junior doctors. We find that careful clinical examination combined with good radiographs should reveal the diagnosis. As closed reduction of bowing fractures may be very difficult to carry out, open reduction may frequently be preferable. PMID- 9989198 TI - [Post-menopausal hormone substitution and ischemic heart disease]. PMID- 9989200 TI - [Good scientific practice]. PMID- 9989199 TI - [George Lundberg, editor of JAMA, sacked by the American Medical Society]. PMID- 9989201 TI - [What is the relation between randomized trials and evidence-based medicine?]. PMID- 9989202 TI - [Public disease a task for a specialist?]. PMID- 9989203 TI - [Thrombolysis in stroke?]. PMID- 9989204 TI - [Treatment of patients with gallstones. An evaluation of medical technology]. PMID- 9989205 TI - AIDS-associated malignancies: research perspectives. AB - The appearance in 1981 of a usually rare malignancy, Kaposi's sarcoma, in homosexual men [1] was one of the first harbingers of an epidemic caused by a retrovirus, human immunodeficiency virus (HIV), which causes the acquired immunodeficiency syndrome (AIDS). Lymphoid and other malignancies were also increased, most strikingly non-Hodgkin's lymphoma and primary central nervous system (CNS) lymphoma. Advances in molecular biology, immunology, virology, and anti-viral therapy have combined to create unique research opportunities. One developing theme is the role of viral co-infection and malignancy. Human herpes virus 8 (HHV8), Epstein-Barr virus (EBV) and papilloma virus each may have a causal role in the development of HIV-associated malignancy. New antiretroviral therapies are able to substantially reverse or delay the profound immunosuppression of HIV infection. The changes in the epidemiology of malignancies, and understanding the mechanism of action of these new therapeutics provide research opportunities to understand the pathogenesis of these malignancies. The opportunities to discover the consequences of T-cell based immunodeficiency and the interactions with specific viral pathogens will likely lead to progress in HIV treatment and new strategies for other malignancies. PMID- 9989206 TI - Genetic epidemiology of prostate cancer. AB - A family history of prostate cancer is a consistent risk factor for prostate cancer, and can also be used to predict the presence of prostate cancer among asymptomatic men who undergo PSA screening. Approximately 5% of cases of prostate cancer have a familial component. The genetic epidemiology of prostate cancer is complex, and genes on chromosome 1 and X chromosome contribute to familial aggregation. Neither of these prostate cancer susceptibility genes have been identified, but are the subject of an active search. Hereditary prostate cancer resembles non-hereditary cancer in terms of age of onset, pathologic appearance and grade. PMID- 9989207 TI - Leukemia: the sophisticated subversion of hematopoiesis by nuclear receptor oncoproteins. PMID- 9989208 TI - Papillomaviruses: prophylactic vaccine prospects. AB - Identification of a subset of HPV types as etiologic agents of cervical cancer and other malignancies implies that development of an effective vaccine against HPV infection could have a major impact on tumors attributable to these viruses. The ability of the L1 major capsid protein of papillomaviruses to self-assemble into VLPs that can, when inoculated systemically, induce high levels of neutralizing antibodies and protect animals against experimental viral challenge makes L1 VLPs an excellent candidate subunit vaccine. VLPs have the limitation of inducing type-specific immunity. Studies in humans are required to determine whether systemic vaccination with L1 VLPs will prevent sexually transmitted HPV infection. Since prospective efficacy trials will take several years to complete, considering alternative approaches is also worthwhile. PMID- 9989209 TI - Genetics of aging. Sponsored by Cold Spring Harbor Laboratory, 2-5 April 1998. PMID- 9989210 TI - Molecular chaperones and the heat shock response. Sponsored by Cold Spring Harbor Laboratory, 6-10 May 1998. PMID- 9989211 TI - Oncogenes and growth control. EMBL-SALK Conference, Heidelberg, Germany, 18-22 April 1998. PMID- 9989213 TI - LXIII Cold Spring Harbor Symposium on Quantitative Biology: Mechanisms of Transcription, 3-8 June 1998. AB - A new perspective is emerging in the transcription field towards understanding gene regulation not only at its most fundamental level but also in the context of chromatin, nuclear compartmentalization, and physiological processes. This direction is being fueled by several key observations. Among them is the discovery of multi-protein complexes whose components reveal a link between gene activity, nuclear structure, and cellular signaling pathways. This information will no doubt be extended by identifying expanded regulatory circuitry using the microchip oligonucleotide array technology. In addition to elucidating the regulatory consequences of these intricate connections, another frontier will be to analyze gene expression within chromosomes. This requires deciphering the mechanism of action of a variety of DNA elements that create a genetic domain such as locus control regions, distal enhancers, insulators, silencers, and matrix attachment regions. Hopefully, with the development of new assays these elements can be as rigorously defined as promoters have been. We can also look forward to capturing critical transcriptional processes by increasingly refined structural analyses. Thus, the scope of problems being addressed in gene regulation has been greatly expanded and the opportunity exists to answer very sophisticated questions in the future. PMID- 9989212 TI - Proteases and cancer invasion: from belief to certainty. AACR meeting on proteases and protease inhibitors in cancer, Nyborg, Denmark, 14-18 June 1998. PMID- 9989214 TI - Protein folding in Escherichia coli: role of 23S ribosomal RNA. AB - Post-translational control of Escherichia coli ribosome on newly synthesised polypeptide leading to its active conformation (protein folding) has been shown in the case of the enzyme beta-galactosidase. As expected, antibiotics chloramphenicol and lincomycin, which bind to 23S rRNA/50S subunit and kasugamycin and streptomycin which interact with the 30S subunit instantaneously inhibited protein synthesis when they were added to the growing cells. The increase in beta-galactosidase activity, though stopped immediately after the addition of chloramphenicol and lincomycin, went on considerably in the presence of streptomycin and kasugamycin even after the stoppage of protein synthesis. PMID- 9989215 TI - The binding of 3,6-disubstituted bile salts to human serum albumin induces conformational change on the molecule of this protein. AB - The binding of 3,6-hydroxy and keto disubstituted bile salts to human serum albumin was studied using differential scanning calorimetry, fluorescence spectroscopy and circular dichroism. The bile salts assayed did not produce any modification in the shape of the albumin thermogram, its thermal unfolding process in their presence being reversible; however, an increase in the enthalpy of unfolding and in the Tm was observed in the presence of 3,6-diketo and 3 hydroxy-6-keto bile salts. These two derivatives induced a negative circular dichroism spectrum of the protein around 280-290 nm, quenched the native fluorescence of the buried tryptophan of albumin and induced energy transfer between 1 aniline-8-naphthalene sulfonate and the buried tryptophan 214 of albumin. The presence of a keto group at C6 in the steroid ring of the bile salts plays an important role in producing slight movement of the albumin domains, increasing the distance between domains I and II. PMID- 9989216 TI - Investigation of the role of surface residues in the ferredoxin from Clostridium pasteurianum. AB - Eleven mutant forms of the ferredoxin from Clostridium pasteurianum (CpFd; 2 Fe4S4; 6200 Da) have been isolated in which six surface carboxylates are changed systematically to their uncharged but stereochemically equivalent carboxamide analogues. Such changes provide molecules which vary in overall charge and its surface distribution but vary minimally in structure and reduction potential. Glu 17 and Asp-6, -27, -33, -35, and -39 were converted providing six single mutants, four double mutants and one triple mutant. The proteins were characterised by UV visible spectroscopy, square-wave voltammetry and 1H NMR. Their ability to mediate electron transfer between spinach NADH:ferredoxin oxidoreductase and horse heart cytochrome c was assessed. Each mutant is 30-100% as active as the recombinant protein with the triple mutant D33,35,39N being least active. Second order rate constants k2 for the oxidation of reduced mutant ferredoxins by [Co(NH3)6]3+ were measured at 25 degrees C and I = 0.1 M by stopped-flow techniques. Each mutant displayed saturation kinetics with k2 being 30-100% of that for the recombinant protein. The rates were moderately sensitive to ionic strength. Variation in association constant K could not be detected within the confidence limits of the data. Overall the effects of the mutations were minor. In contrast to human and Anabaena 7120 [Fe2S2]-ferredoxins, electron transfer does not appear to rely on the presence of one or two specific surface carboxylate residues. It may occur from multiple sites on the surface of CpFd with recognition processes for its many physiological redox partners being controlled by relative reduction potentials, in addition to unidentified criteria. The conclusions are consistent with previous results for another series of mutant CpFd proteins interacting with physiological redox partners pyruvate: Fd oxidoreductase and hydrogenase (J.M. Moulis, V. Davasse (1995) Biochemistry 34, 16781-16788). PMID- 9989218 TI - Cloning of a cDNA encoding SjIrV1, a Schistosoma japonicum calcium-binding protein similar to calnexin, and expression of the recombinant protein in Escherichia coli. AB - Membrane-associated proteins were isolated from adult Philippine strain Schistosoma japonicum by partitioning into the detergent phase of Triton X-114. A rabbit polyclonal antiserum raised against these proteins was used to screen an S. japonicum expression cDNA library. Positive clones were identified which encoded the species orthologue of SmIrV1, a Schistosoma mansoni protein which was initially identified by screening with sera from mice protectively vaccinated with irradiated cercariae [Hawn et al., J. Biol. Chem. 268 (1993) 7692-7698]. The S. japonicum molecule, which we term SjIrV1, is 83% identical to SmIrV1 at the predicted amino acid level and is a member of the calreticulin family of non-EF hand, calcium-binding proteins. The Chinese strain S. japonicum orthologue of SjIrV1 was obtained by screening with the radiolabelled insert of the Philippine strain clone. Northern blot analysis revealed a single message of around 2.4 kb and gave no indication of alternative splicing. Southern blot analysis gave a simple pattern, indicating a single-copy gene, and showed a single restriction fragment length polymorphism between the genomes of Chinese and Philippine strains of S. japonicum. Recombinant, full-length SjIrV1 was expressed with a hexahistidine tag in Escherichia coli and the recombinant protein isolated by nickel-chelate chromatography. Recombinant SjIrV1 was shown to exhibit calcium dependent, differential electrophoretic migration and to bind ruthenium red in the absence but not in the presence of calcium ions. The presence of conserved Ca(2+)-binding motifs predicted from the primary sequence, together with the Ca(2+)-dependent electrophoretic mobility of recombinant SjIrV1, confirmed that SjIrV1 was a functional calcium-binding protein. PMID- 9989217 TI - Time-resolved fluorescence of O-acetylserine sulfhydrylase. AB - Static and time-resolved fluorescence of the internal aldimine of the pyridoxal 5'-phosphate (PLP)-dependent enzyme O-acetylserine sulfhydrylase (OASS) and those of free PLP, and the PLP-L-valine Schiff base have been measured to gain insight into the photophysics of PLP bound to OASS. Exciting at 330 nm, free coenzyme exhibits a band at 415 nm, whereas PLP-valine and OASS (also when excited at their absorbance maxima) exhibit a structured emission with a peak at 420 nm and shoulders at 490 and 530 nm. The emission bands at 420 and 490 nm are attributed to the enolimine and ketoenamine tautomers of the internal aldimine, respectively, while the 530 nm emission might arise from a dipolar species formed upon proton dissociation in the excited state. Time-resolved fluorescence of OASS (PLP-valine), excited at 412 nm (415 nm) and collected at lamda > 470 nm, indicates the presence of two components characterized by lifetimes (tau) of 0.6 (0.08) and 3.8 (1.55) ns with equal fractional intensity (f). In the presence of acetate the slow component dominates OASS emission with f of 0.98. Excitation at 350 nm as a function of emission wavelengths (400-560 nm) shows at least three components. The f of the slow component increases from 400 to 440 nm, then decreases, whereas the f of the intermediate and fast components behave in the opposite way. Results indicate that: (i) the fast component is associated with the emission at 530 nm; (ii) the slow component is associated with the emission at 420 nm; (iii) a fast additive component, characterized by a very short lifetime, is present on the blue side of the emission spectrum; (iv) the intermediate component results from overlapping contributions, including the emission of the band at 490 nm, that could not be resolved; (v) the increased emission at 490 nm, caused by acetate binding, is likely due to the stabilization of the ketoenamine tautomer induced by an increase in polarity of the active site microenvironment and/or a decrease in proton dissociation in the excited state; (vi) excitation at 330 nm, where the enolimine tautomer absorbs, leads to emission decays typical of the ketoenamine. PMID- 9989219 TI - The oligomeric state of Bacillus thuringiensis Cry toxins in solution. AB - The molecular mass of different Cry toxins produced by Bacillus thuringiensis bacteria was estimated by size-exclusion chromatography and non-denaturing polyacrylamide gel electrophoresis at neutral and alkaline pH in order to assess the existence of oligomers in solution. We found that Cry1Aa, Cry1Ac, Cry1C, Cry1D and Cry3A toxins exist in solution as a mixture of monomer and high molecular mass aggregates with an apparent molecular mass greater than 600 kDa, that depend on the time elapsed between toxin activation and analysis. Aggregation of toxins by disulfide bonds is unlikely because aggregates are also observed in samples incubated with DTT. These data show that the Cry toxins studied do not form oligomers of less than ten subunits in solution and suggest that oligomer formation may occur after the toxin binds to the receptor and inserts into the membrane. PMID- 9989220 TI - X-ray absorption spectroscopy of cadmium phytochelatin and model systems. AB - Higher plants, algae and some yeasts respond to potentially toxic heavy metals such as cadmium by synthesizing phytochelatins and related cysteine-rich polypeptides. We have used X-ray absorption spectroscopy to study the nature of cadmium binding in such peptides isolated from maize (Zea mays) exposed to low levels of cadmium, and in two synthetic cadmium-peptide complexes, Cd-(gamma-Glu Cys)3Gly and Cd-(alpha-Glu-Cys)3Gly. We have used the synthetic ions [Cd(SPh)4]2 , [Cd4(SPh)10]2- and [S4Cd10(SPh)16]4-as crystallographically defined models for the cadmium site. The Cd K-edge extended X-ray absorption fine structure (EXAFS) data, together with the Cd K, LI, LII and LIII near-edge spectra, reveal a predominantly tetrahedral coordination of cadmium by sulfur in both the phytochelatin and synthetic peptide complexes. In particular, the Cd LIII-edge lacks a peak at 3534.9 e V which was found to be prominent for oxygen- or nitrogen-coordinated species. The Cd-S distance in the phytochelatin complex is 2.54 A. The Cd K-edge EXAFS does not show any isolated, well-defined Cd-Cd interactions; however, contrary to the conclusion of previous work, their absence is not necessarily indicative of isolated cadmium-thiolate ligation. Evidence from other studies suggests that high static disorder, combined with a large vibrational component, serve to effectively wash out this contribution to the EXAFS. The sulfur K-edge, moreover, shows a low-energy feature both in the phytochelatin and in the synthetic cadmium-peptide complexes which is consistent with sulfide bound in a cluster with cadmium as found for [S4Cd10(SPh)16]4-. This feature strongly suggests the presence of a polynuclear cadmium cluster in maize phytochelatin. PMID- 9989221 TI - Thermal unfolding of chitosanase from Streptomyces sp. N174: role of tryptophan residues in the protein structure stabilization. AB - Tryptophan residues in chitosanase from Streptomyces sp. N174 (Trp28, Trp101, and Trp227) were mutated to phenylalanine, and thermal unfolding experiments of the proteins were done in order to investigate the role of tryptophan residues in thermal stability. Four types of mutants (W28F, W101F, W227F and W28F/W101F) were produced in sufficient quantity in our expression system using Streptomyces lividans TK24. Each unfolding curve obtained by CD at 222 nm did not exhibit a two-state transition profile, but exhibited a biphasic profile: a first cooperative phase and a second phase that is less cooperative. The single tryptophan mutation decreased the midpoint temperature (Tm) of the first transition phase by about 7 degrees C, and the double mutation by about 11 degrees C. The second transition phase in each mutant chitosanase was more distinct and extended than that in the wild-type. On the other hand, each unfolding curve obtained by tryptophan fluorescence exhibited a typical two-state profile and agreed with the first phase of transition curves obtained by CD. Differential scanning calorimetry profiles of the proteins were consistent with the data obtained by CD. These data suggested that the mutation of individual tryptophan residues would partly collapse the side chain interactions, consequently decreasing Tm and enhancing the formation of a molten globule-like intermediate in the thermal unfolding process. The tryptophan side chains are most likely to play important roles in cooperative stabilization of the protein. PMID- 9989222 TI - Parameter estimation using a direct solution of the integrated Michaelis-Menten equation. AB - A novel method of estimating enzyme kinetic parameters is presented using the Lambert omega function coupled with nonlinear regression. Explicit expressions for the substrate and product concentrations in the integrated Michaelis-Menten equation were obtained using the omega function which simplified kinetic parameter estimation as root-solving and numerical integration of the Michaelis Menten equation were avoided. The omega function was highly accurate in describing the substrate and product concentrations in the integrated Michaelis Menten equation with an accuracy of the order of 10(-16) when double precision arithmetic was used. Progress curve data from five different experimental systems were used to demonstrate the suitability of the omega function for kinetic parameter estimation. In all cases, the kinetic parameters obtained using the omega function were almost identical to those obtained using the conventional root-solving technique. The availability of highly efficient algorithms makes the computation of omega simpler than root-solving or numerical integration. The accuracy and simplicity of the omega function approach make it an attractive alternative for parameter estimation in enzyme kinetics. PMID- 9989223 TI - Cold denaturation of ubiquitin. AB - Temperature induced unfolding of bovine ubiquitin in solutions with different concentrations of guanidinium hydrochloride (GdmCl) has been measured using differential scanning calorimetry. It has been shown that at high concentrations of GdmCl the ubiquitin molecule can undergo both heat and cold induced denaturation. Analysis of the enthalpy of unfolding of ubiquitin in the presence of GdmCl shows a good agreement with the thermodynamic denaturant binding model. The unfolding Gibbs energy is found to change linearly with guanidine concentration up to zero denaturant concentration. PMID- 9989224 TI - Investigation of the binding interactions of progesterone using muteins of the human progesterone receptor ligand binding domain designed on the basis of a three-dimensional protein model. AB - The aim of this study was to investigate the binding interactions of the human progesterone receptor (hPR) with its natural ligand. Therefore, a homology derived model of the hPR ligand binding domain has been constructed and used to predict residues potentially involved in interactions with progesterone. These residues and the free cysteines have been mutated (in total 13 residues with 15 mutations). All exchanges have been designed to preserve the three-dimensional structure of the protein. With respect to the binding characteristics towards progesterone, the muteins fall into three groups displaying no, reduced, or wildtype-like binding activity. PMID- 9989225 TI - High expression and steady-state kinetic characterization of methionine site directed mutants of Escherichia coli methionyl- and selenomethionyl-dihydrofolate reductase. AB - A high expression system that produces Escherichia coli dihydrofolate reductase (DHFR) at 30% total cellular protein was constructed. This expression vector, named pCOCK, allowed for the purification of nearly 100 mg of homogeneous DHFR from a 11 bacterial culture. A simple, single Q-Sepharose anion exchange column purification was developed on an FPLC instrument. Methionine site-directed mutants were constructed in DHFR to assess the role of Met within the enzymes. These mutants consisted of a Met16leucine (Leu), Met20Leu, Met42Leu, Met92Leu, Met16,20Leu and Met16,20,42Leu. Steady-state kinetic studies showed that the Met16Leu, Met42Leu and Met92Leu mutants possessed essentially the same kcat, Km(DHF) and Km(NADPH) as that of wild-type (wt) DHFR (13.7 s-1, 0.97 microM and 2.52 microM, respectively). Mutants which contained a Leu at position 20 possessed substantially elevated specific activity and kcat values. The specific activity and kcat of wt, Met20Leu, Met16,20Leu and Met16,20,42Leu were 45.9, 92.7, 90.2 and 172 mumol/min/mg and 13.7, 24.6, 25.2 and 52.7 s-1, respectively. Upon substitution of Met by selenomethionine (SeMet) in the aforementioned mutants, further information as to the effect of SeMet incorporation into proteins was ascertained. Steady-state kinetic parameters of the SeMet substituted Met16Leu, Met20Leu, Met42Leu and Met92Leu mutants were nearly identical to those of their Met containing counterparts. These data indicate that Met apparently has a limited role in the protein structure and function of DHFR and that SeMet incorporation has no effect on the steady-state kinetic constants of DHFR. PMID- 9989226 TI - Thermodynamics of nucleotide interactions with the Azotobacter vinelandii nitrogenase iron protein. AB - The nitrogenase iron (Fe) protein binds two molecules of MgATP or MgADP, which results in protein conformational changes that are important for subsequent steps of the nitrogenase reaction mechanism. In the present work, isothermal titration calorimetry has been used to deconvolute the apparent binding constants (K'a1 and K'a2) and the thermodynamic terms (delta H' degree and delta S' degree) for each of the two binding events of MgATP or MgADP to either the reduced or oxidized states of the Fe protein from Azotobacter vinelandii. The Fe protein was found to bind two nucleotides with positive cooperativity and the oxidation state of the [4Fe-4S] cluster of the Fe protein was found to influence the affinity for binding nucleotides, with the oxidized ([4Fe-4S]2+) state having up to a 15-fold higher affinity for nucleotides when compared to the reduced ([4Fe-4S]1+) state. The first nucleotide binding reaction was found to be driven by a large favorable entropy change (delta S' degree = 10-21 cal mol-1 K-1), with a less favorable or unfavorable enthalpy change (delta H' degree = +1.5 to -3.3 kcal mol-1). In contrast, the second nucleotide binding reaction was found to be driven by a favorable change in enthalpy (delta H' degree = -3.1 to -13.0 kcal mol-1), with generally less favorable entropy changes. A plot of the associated enthalpy ( delta H' degree) and entropy terms (-T delta S' degree) for each nucleotide and protein binding reaction revealed a linear relationship with a slope of 1.12, consistent with strong enthalpy-entropy compensation. These results indicate that the binding of the first nucleotide to the nitrogenase Fe protein results in structural changes accompanied by the reorganization of bound water molecules, whereas the second nucleotide binding reaction appears to result in much smaller structural changes and is probably largely driven by bonding interactions. Evidence is presented that the total free energy change (delta G' degree) derived from the binding of two nucleotides to the Fe protein accounts for the total change in the midpoint potential of the [4Fe-4S] cluster. PMID- 9989227 TI - Polyol-induced activation by excess substrate of the D70G butyrylcholinesterase mutant. AB - Wild-type human butyrylcholinesterase (BuChE) has a non-Michaelian behaviour showing substrate activation with butyrylthiocholine (BTC) as the substrate. The D70G mutant has a catalytic constant identical to that of the wild-type enzyme, but a 10-fold lower affinity for BTC compared to wild-type enzyme, and it does not exhibit activation by excess BTC under conventional conditions. In the present work it was found that addition of polyols or sugars changed the kinetic behaviour of the D70G mutant with BTC. In the presence of 40% sucrose, the D70G mutant enzyme displayed marked activation by excess substrate. Because D70 is hydrogen bonded to Y332, mutants of Y332 were studied. Mutant Y332F had a behaviour similar to that of wild-type BuChE, whereas mutants Y332A, Y332A/D70G and D70G had negligible substrate activation. The behavior of wild-type, Y332F, Y332A and Y332A/D70G did not change in the presence of high concentrations of sugar. Substrate activation has been explained by binding of a second substrate molecule in the peripheral site at D70. The D70G mutant should be incapable of substrate activation, if D70 were the only residue involved in substrate activation. The ability of the D70G mutant to display substrate activation by medium engineering suggests that other residues are involved in initial substrate binding and activation by excess substrate. Osmolyte-induced change in conformation and/or hydration status of Y332 and other solvent-exposed residues may account for the non-Michaelian behaviour of the D70G mutant. PMID- 9989228 TI - Partial sequence of human platelet heparitinase and evidence of its ability to polymerize. AB - Heparitinase cleaves heparan sulfate, a glycosaminoglycan associated with all nucleated mammalian cells and extracellular matrices. Despite the important physiologic role heparitinase is postulated to play in such processes as tumor metastasis and inflammation, the identity of the enzyme remains a matter of controversy and there is a question of whether heparitinase is CTAP III. We report a 900,000-fold purification of heparitinase from human platelets. A multi step procedure utilizing chromatography on heparin, DEAE, hydroxyapatite and size exclusion matrices was employed and yielded a single protein as judged by Coomassie staining of protein separated by SDS-PAGE. The purified protein had an apparent molecular mass of 35 kDa by size exclusion chromatography and 55 kDa by SDS-PAGE. During purification, heparitinase activity co-eluted from the hydroxyapatite and size exclusion columns with the 35-55 kDa protein, confirming that the purified protein was indeed heparitinase. The 35-55 kDa protein reacted strongly with concanavalin A, a lectin known to bind to heparitinase, further confirming that the protein was heparitinase. Platelet heparitinase formed dimers and tetramers upon storage in a purified form, possibly accounting for the various molecular weights previously reported for the enzyme. A partial amino acid sequence of the protein revealed that heparitinase has not been previously sequenced. PMID- 9989229 TI - Purification and characterization of a new enzyme, N-alkylglycine oxidase from Cladosporium sp. G-10. AB - A new enzyme, N-alkylglycine oxidase, was isolated from a soil mold, Cladosporium sp. G-10. This protein, which was purified to near homogeneity by ammonium sulfate precipitation followed by successive column chromatography on phenyl Sepharose, DEAE-Sepharose and Sephadex G-200, was a single polypeptide with a molecular mass of 52,000. In the presence of O2 and H2O, this enzyme acted on some N-alkylglycine derivatives, such as N epsilon-carboxymethyllysine, N carboxymethyl-6-aminocaproic acid, sarcosine and N-ethylglycine, and produced corresponding N-alkylamine, glyoxylic acid and H2O2. This enzyme had optimum activity at 30 degrees C, pH 8-10, and was most inhibited by ZnSO4, pCMB, iodoacetic acid, and SDS. PMID- 9989230 TI - Glycerol's influence on the oxidized insulin B-chain conformation in relation to the selectivity variation of subtilisin: an nuclear magnetic resonance and simulated annealing study. AB - Glycerol, employed to mimic biological media with restricted water activity, has been shown to modify the activity of subtilisin BPN', an endopeptidase, towards the oxidized insulin B-chain, a well-studied substrate (FEBS Lett., 279 (1991) 123-131). Without minimizing the role of the microenvironment on the enzyme, we have studied the effect of glycerol addition on the structure of the enzyme substrate by homonuclear NMR spectroscopy and simulated annealing. Our results show that, in water, the oxidized insulin B-chain tertiary structure loses its central helix (residues B9-B19) and presents a folded structure with a flexible turn (residues B18-B24) in the beta-turn region of the insulin B-chain; whereas, in glycerol, the peptide is more rigid and is not folded. Moreover, in our experimental conditions, glycerol favors beta-strand secondary structure formation. Following these results, hypotheses about the differences observed in enzymatic activity on this substrate in glycerol have been postulated. PMID- 9989232 TI - High density lipoprotein (HDL), and not albumin, is the major palmitate binding protein in New Zealand long-finned (Anguilla dieffenbachii) and short-finned eel (Anguilla australis schmidtii) plasma. AB - Plasma from two members of the teleost Anguillidae family, the New Zealand long finned (Anguilla dieffenbachii) and short-finned eels (Anguilla australis schmidtii), were examined. Agarose gel electrophoresis showed both species had a major anionic diffuse protein band migrating at approximately the same position as human albumin, and autoradiography showed this protein bound [14C]palmitic acid, but not 63Ni2+. Cellulose acetate electrophoresis followed by Oil Red O staining suggested that this band was a lipoprotein. Two-dimensional electrophoresis of plasma showed the absence of a significant albumin band at approx. 65 kDa, and that the palmitate binding band appeared to be composed of at least three proteins, with the major protein running at 30 kDa. N-Terminal sequencing of the palmitate binding band indicated major sequences of DAPAPP(S)QLED- for long-finned eel and DAPAPPSQLEHV- for short-finned eel, confirming their identities as apo-AI, the major apolipoprotein of high density lipoprotein (HDL). When ultracentrifugation was used to separate the lipoproteins of each species, the anionic palmitate binding protein was found solely in the lipoprotein fractions. There was no evidence of albumin in plasma from either eel, and it appears that in its absence HDL takes on the role of fatty acid transport. PMID- 9989231 TI - Altering the state of phosphorylation of rat liver keratin intermediate filaments by ethanol treatment in vivo changes their structure. AB - Dephosphorylation of keratin intermediate filaments (IF) in livers from ethanol fed rats relative to controls occurs concurrently with a reorganization of the distribution of IF in the cells. One possible molecular mechanism for this reorganization is a phosphorylation-induced conformational change in the keratin that propagates as a change in the polymerization of the keratin subunits. To test this hypothesis, the structure of liver keratin IF, from both control and alcohol-fed rats, was explored by circular dichroism (CD), tryptophan fluorescence quenching, and 13C nuclear magnetic resonance (NMR). Keratin IF were isolated from livers of control rats and from livers of rats that had ethanol included in their feed for 6-40 weeks. A significant decrease in the intensity of the CD spectrum of keratin IF from livers of ethanol-treated animals, relative to controls, was observed. These data suggested either that a change in conformation or an increase in conformational motility in the keratin IF from ethanol-treated animals occurred as a result of the ethanol-induced dephosphorylation. 13C NMR data were obtained to distinguish between these two possibilities. An increase in resonance intensity of some 13C NMR resonances was observed in the keratin IF from livers of ethanol-treated animals, relative to controls. The CD and NMR data were therefore consistent with an increase in conformational motility of the rod domain in these keratin IF. No significant change was observed in the quenching of tryptophan fluorescence by KI. The change in protein dynamics detected in these experiments could be the molecular basis for the alteration of keratin IF organization in alcoholic hepatitis. PMID- 9989233 TI - A comparative molecular field analysis study on several bioactive peptides using the alignment rules derived from identification of commonly exposed groups. AB - A 3D convex hull computation algorithm designed by us previously is used as a tool to align a series of structures randomly generated for eleven bioactive tachykinin peptides. There are 10 random structures generated for each peptide. A random structure is selected for each peptide to form a structural set of eleven structures. The total number of structural sets generated is 100. The convex hull computation algorithm is applied to each peptide structure generated. We count the frequency of atoms lying on the vertices of each hull computed. Vertices of the same atom type are gathered together as a set of commonly exposed atoms for a structural set generated. Structures are then aligned by treating the set of commonly exposed atoms as a set of correspondences using the FIT option of the SYBYL 6.4 program. All the structure sets are also aligned by using the coordinates of the backbone C alpha atoms as a set of correspondences through the same program. It is found that while a smaller degree of structural similarity for structures aligned by the convex hull alignment rule is detected, the overall SYBYL comparative molecular field analysis (CoMFA) statistics computed for the aligned structures using the alignment rule is better than that computed for the aligned structures using the C alpha atoms alignment rule. A similar conclusion is drawn for a subset of structures selected and probed by a different type of atoms using the SYBYL CoMFA program. These results indicate that computation of 3D convex hulls is a feasible way that one can use to align structures generated for highly flexible molecules of this kind. PMID- 9989234 TI - Dynamic equilibrium unfolding pathway of human tumor necrosis factor-alpha induced by guanidine hydrochloride. AB - The dynamic equilibrium unfolding pathway of human tumor necrosis factor-alpha (TNF-alpha) during denaturation at different guanidine hydrochloride (GdnHCl) concentrations (0-4.2 M) was investigated by steady-state fluorescence spectroscopy, potassium iodide (KI) fluorescence quenching, far-UV circular dichroism (CD), picosecond time-resolved fluorescence lifetime, and anisotropy decay measurements. We utilized the intrinsic fluorescence of Trp-28 and Trp-114 to characterize the conformational changes involved in the equilibrium unfolding pathway. The detailed unfolding pathway under equilibrium conditions was discussed with respect to motional dynamics and partially folded structures. At 0 0.9 M [GdnHCl], the rotational correlation times of 22-25 ns were obtained from fluorescence anisotropy decay measurements and assigned to those of trimeric states by hydrodynamic calculation. In this range, the solvent accessibility of Trp residues increased with increasing [GdnHCl], suggesting the slight expansion of the trimeric structure. At 1.2-2.1 M [GdnHCl], the enhanced solvent accessibility and the rotational degree of freedom of Trp residues were observed, implying the loosening of the internal structure. In this [GdnHCl] region, TNF alpha was thought to be in soluble aggregates having distinct conformational characteristics from a native (N) or fully unfolded state (U). At 4.2 M [GdnHCl], TNF-alpha unfolded to a U-state. From these results, the equilibrium unfolding pathway of TNF-alpha, trimeric and all beta-sheet protein, could not be viewed from the simple two state model (N-->U). PMID- 9989235 TI - Tripeptidyl-peptidase I is apparently the CLN2 protein absent in classical late infantile neuronal ceroid lipofuscinosis. AB - We report that fragments of amino acid sequence recently described for tripeptidyl-peptidase I (TPP I) show that it is the rat homologue of the human CLN2 gene product that is deficient in classical late-infantile neuronal ceroid lipofuscinosis. This is unexpected, since the CLN2 protein has been thought to be a carboxyl-dependent endopeptidase, but TPP I is an exopeptidase possibly of serine-type. PMID- 9989237 TI - Purification, crystallisation and preliminary X-ray diffraction study of ribosome inactivating protein: saporin. AB - We report here the crysallisation and molecular replacement results on the structure determination of S-9 isoform of the ribosome inactivating protein saporin. The protein was purified to homogeneity by a simple and efficient protocol. The crystals belong to the space group I4l with a = b = 91.47 A, c = 150.66 A and contain two molecules in the asymmetric unit. PMID- 9989236 TI - The prolyl aminopeptidase from Lactobacillus delbrueckii subsp. bulgaricus belongs to the alpha/beta hydrolase fold family. AB - Prolyl aminopeptidase (PepIP) of Lactobacillus delbrueckii subsp. bulgaricus displays the Gly-x-Ser-x-Gly-Gly consensus motif surrounding the catalytic serine of the prolyl oligopeptidases family. Sequence comparison revealed that this motif and two other domains appear well conserved among bacterial PepIPs and members of the alpha/beta hydrolase fold family. Secondary structural predictions of PepIP were performed from amino acid sequence and corroborated by circular dichroism analysis. These predictions well matched the core structure of alpha/beta hydrolases organised in eight beta-sheets connected by alpha-helices. We obtained 26 mutants of PepIP by chemical or site-directed mutagenesis. Most substitutions associated with stable and inactive mutant proteins were mainly located in the three conserved boxes (including the catalytic serine motif). Taken together, our results strongly suggest that PepIP belongs to the alpha/beta hydrolase fold family and that Ser107, Asp246 and His273 constitute the catalytic triad of the enzyme. PMID- 9989238 TI - cDNA sequence and overexpression of chloroplast chaperonin 21 from Arabidopsis thaliana. AB - Higher plant chloroplasts contain a 21-kDa protein, chaperonin 21 (Cpn21), that is a functional homolog of the chaperonin 10 (Cpn10). The chloroplast Cpn21 polypeptide consists of two Cpn10-like domains fused together in tandem. We describe here the cDNA sequence of the Cpn21 (AtCpn21) precursor protein from Arabidopsis thaliana. The deduced amino acid sequence of the AtCpn21 precursor protein, 253 amino acids long, shows 61% identity with the spinach Cpn21 protein. The AtCpn21 precursor protein contains the typical chloroplast transit peptide of 51 amino acids at its aminoterminus and the two Cpn10-like domains which exhibits 46% sequence identity to each other. The predicted mature-sized polypeptide of AtCpn21 was expressed in Escherichia coli as a soluble 21-kDa protein. Gel filtration and chemical cross-linking analyses showed that the recombinant mature AtCpn21 protein forms a stable homo-oligomer composed of three or four polypeptides. PMID- 9989239 TI - Cloning of a novel prolidase gene from Aureobacterium esteraromaticum. AB - The prolidase gene from Aureobacterium esteraromaticum was cloned and expressed in Escherichia coli. The cloned enzyme had the same enzymatic properties as the wild-type enzyme. Kinetic analysis of the enzyme indicated that the best substrate was Pro-Hyp, which was not hydrolyzed by other prolidases. Interestingly, there was no homology between the deduced amino acid sequence of A. esteraromaticum prolidase and those of the other sources such as human E. coli and Lactobacillus. However, homology was seen with the yeast hypothetical protein YJL213w, the function of which is unknown. These findings indicate that the A. esteraromaticum prolidase is a novel enzyme different from other prolidases reported to date. PMID- 9989240 TI - Mammalian cell expression of malaria merozoite surface proteins and experimental DNA and RNA immunisation. AB - The gene for a 45 kDa merozoite surface protein (MSA-2) of the human malaria parasite Plasmodium falciparum was PCR amplified and cloned into eukaryotic expression vectors VR1012 and pcDNA3 to yield plasmids P1 and P2, respectively. The coding sequences for two N-terminal fragments of the 185 kDa merozoite surface protein (MSA-1) gene were similarly PCR amplified and cloned into vectors VR1020 and VR1012 to yield plasmids P3 and P4, respectively. The MSA-1 signal peptide sequence, present in P4, was replaced with the human tissue plasminogen activator signal sequence in P3. The four plasmids expressed the cloned genes under the control of the cytomegalovirus promoter and carried 3' bovine growth hormone termination/poly A signals. P1, P3 and P4 also contained the cytomegalovirus intron A enhancer sequence. MSA-1 expression was more readily detected than MSA-2 in Cos cells transfected with P3/P4 and P1/P2 respectively. The MSA-2 gene was also cloned into the phagemid pBluescript IISK+ with and without a 3' poly A tail composed of 35 A residues. MSA-2 was synthesised in HeLa cells infected with a recombinant vaccinia virus carrying T7 RNA polymerase when MSA-2 recombinant pBluescript was transfected into the cells. Inoculation with P1 intramuscularly or intradermally and with P2 intradermally into rabbits led to the production of antibodies to MSA-2 detectable by immunofluorescence and Western blotting. Antibodies were also produced against MSA-1 after intramuscular/intradermal inoculation with P3 and P4. Inoculation of rabbits with MSA-2 mRNA yielded better antibody titres when a poly A tail was present. Antibody levels were maintained for > 9 weeks after the final immunisation. However the immune sera failed to inhibit in vitro parasite growth. PMID- 9989242 TI - Cation-mediated conformational variants of surfactant protein A. AB - Surfactant protein A (SP-A) is the major protein of pulmonary surfactant. This protein is implicated in regulating surfactant secretion, alveolar processing, recycling, and in non-serum-induced immune response. An increasing body of work indicates the importance of cations, particularly calcium, on SP-A function. However, little information exists on the effects of cations on SP-A quaternary structure. Here, the quaternary organisation of bovine surfactant protein A in the presence of cations has been quantitatively and systematically studied by transmission electron microscopy. The conformation of SP-A is altered by the presence of cations, especially calcium, then sodium, and to a small extent, magnesium. There is a transition concentration, unique for each cation, at which a conformational switch occurs. These transition concentrations are: 5 mM for CaCl2, 100 mM for NaCl and 1 mM for MgCl2. Below these concentrations, SP-A exists primarily in an opened form with a large head diameter of 20 nm; above it, SP-A is mostly in a closed form due to a compaction of the headgroups resulting in a head diameter of 11 nm. There is a corresponding increase in particle length from 17 nm for opened SP-A to 20 nm for closed SP-A. The fact that the transition concentrations are within physiological range suggests that cation-mediated conformational changes of SP-A could be operative in vivo. PMID- 9989241 TI - High lysosomal activities in cystic fibrosis tracheal gland cells corrected by adenovirus-mediated CFTR gene transfer. AB - Human tracheal gland serous (HTGS) cells are now believed to be a major target of cystic fibrosis (CF) gene therapy. To evaluate the efficiency of adenovirus mediated gene transfer in these cells we tested the adenovirus construction containing beta-galactosidase cDNA. We observed that the endogenous beta galactosidase activity in cultured CF-HTGS cells was too strong to allow us to detect any exogenous beta-galactosidase activity. Immunohistological study on sections of human tracheal tissue confirmed the presence of beta-galactosidase in the serous component of the submucosal glands. We then looked for other lysosomal activities in normal and CF-HTGS cells. We showed that normal cells already have elevated enzyme values and that CF-HTGS cells contained 2-4-fold more beta galactosidase, alpha-fucosidase, alpha-mannosidase and beta-glucuronidase activities than normal cells. An analysis of their kinetic constants has shown that this difference could be attributed to a lower K(m) of CF lysosomal enzymes. More importantly, these differences are eliminated after adenovirus-mediated CFTR gene transfer and not after beta-galactosidase gene transfer. PMID- 9989243 TI - Enhanced tumor necrosis factor-alpha production following endotoxin challenge in rats is an early event during magnesium deficiency. AB - Magnesium (Mg) plays an essential role in fundamental cellular reactions and the importance of the immuno-inflammatory processes in the pathology of Mg deficiency has been recently reconsidered. The purpose of the present study was to assess the effect of different stages of Mg deficiency on endotoxin response and tumor necrosis factor-alpha (TNF alpha) production. Weaning male Wistar rats were pair fed either a Mg-deficient or a control diet. At day 7, lipopolysaccharide (LPS) induced no lethal effects in control rats but resulted in 70% mortality in Mg deficient rats within 3 h. The vulnerability of Mg-deficient rats to LPS was associated with higher TNF alpha plasma values. Mg-deficient animals that received magnesium supplementation before endotoxin challenge had significantly increased survival. At day 2, control and Mg-deficient rats were also subjected to endotoxin challenge with or without magnesium pre-treatment. A significant increase in TNF alpha plasma level was observed in Mg-deficient rats compared to rats fed the control diet. Mg-deficient rats that received magnesium replacement therapy before endotoxin challenge had significantly lower TNF alpha plasma values than those receiving saline before endotoxin. Thus, the results of this experiment suggest that the activated or primed state of immune cells is an early event occurring in Mg deficiency. PMID- 9989244 TI - Release of cytochrome c from heart mitochondria is induced by high Ca2+ and peroxynitrite and is responsible for Ca(2+)-induced inhibition of substrate oxidation. AB - Prolonged heart ischaemia causes an inhibition of oxidative phosphorylation and an increase of Ca2+ in mitochondria. We investigated whether elevated Ca2+ induces changes in the oxidative phosphorylation system relevant to ischaemic damage, and whether Ca2+ and other inducers of mitochondrial permeability transition cause the release of cytochrome c from isolated heart mitochondria. We found that 5 microM free Ca2+ induced changes in oxidative phosphorylation system similar to ischaemic damage: increase in the proton leak and inhibition of the substrate oxidation system related to the release of cytochrome c from mitochondria. The phosphorylating system was not directly affected by high Ca2+ and ischaemia. The release of cytochrome c from mitochondria was caused by Ca2+ and 0.175-0.9 mM peroxynitrite but not by NO, and was prevented by cyclosporin A. Adenylate kinase and creatine kinase were also released after incubation of mitochondria with Ca2+, however, the activity of citrate synthase in the incubation medium with high and low Ca2+ did not change. The data suggest that release of cytochrome c and other proteins of intermembrane space may be due to the opening of the mitochondrial permeability transition pore, and may be partially responsible for inhibition of mitochondrial respiration induced by ischaemia, high calcium, and oxidants. PMID- 9989245 TI - The parkinsonian neurotoxin MPP+ opens the mitochondrial permeability transition pore and releases cytochrome c in isolated mitochondria via an oxidative mechanism. AB - The mitochondrial transition pore (MTP) is implicated as a mediator of cell injury and death in many situations. The MTP opens in response to stimuli including reactive oxygen species and inhibition of the electron transport chain. Sporadic Parkinson's disease (PD) is characterized by oxidative stress and specifically involves a defect in complex I of the electron transport chain. To explore the possible involvement of the MTP in PD models, we tested the effects of the complex I inhibitor and apoptosis-inducing toxin N-methyl-4 phenylpyridinium (MPP+) on cyclosporin A (CsA)-sensitive mitochondrial swelling and release of cytochrome c. In the presence of Ca2+ and Pi, MPP+ induced a permeability transition in both liver and brain mitochondria. MPP+ also caused release of cytochrome c from liver mitochondria. Rotenone, a classic non competitive complex I inhibitor, completely inhibited MPP(+)-induced swelling and release of cytochrome c. The MPP(+)-induced permeability transition was synergistic with nitric oxide and the adenine nucleotide translocator inhibitor atractyloside, and additive with phenyl arsine oxide cross-linking of dithiol residues. MPP(+)-induced pore opening and cytochrome c release were blocked by CsA, the Ca2+ uniporter inhibitor ruthenium red, the hydrophobic disulfide reagent N-ethylmaleimide, butacaine, and the free radical scavenging enzymes catalase and superoxide dismutase. MPP+ neurotoxicity may derive from not only its inhibition of complex I and consequent ATP depletion, but also from its ability to open the MTP and to release mitochondrial factors including Ca2+ and cytochrome c known to be involved in apoptosis. PMID- 9989246 TI - Mechanism of interaction of thrombospondin with human endothelium and inhibition of sickle erythrocyte adhesion to human endothelial cells by heparin. AB - Thrombospondin (TSP) mediates sickle erythrocyte adhesion to endothelium, but the mechanism remains unknown. Since TSP is comprised of heterogeneously distinct domains, this adhesion may depend on the interaction of specific regions of TSP with different cell surface receptors. To examine the mechanisms of interaction of TSP with human umbilical vein endothelial cells (HUVEC), we performed binding studies using soluble [125I]TSP. Our data showed that (i) monoclonal antibodies (MoAbs) against cell surface heparan sulfate (HS) or the heparin-binding domain of TSP, or cleavage of HS on HUVEC by heparitinase reduced TSP binding by 28-40%, (ii) the RGD peptide or MoAbs against integrin alpha v beta 3 or the calcium binding region of TSP inhibited binding by 18-28%, and (iii) a MoAb against the cell-binding domain of TSP inhibited binding by 36%. Unmodified heparin inhibited the binding of TSP to endothelial cells by 70% and did so far more effectively than selectively desulfated heparins, HS or chondroitin sulfate. Heparin inhibited TSP binding to HUVEC at much lower concentrations than were required to inhibit TSP binding to sickle erythrocytes. Unmodified heparin effectively inhibited the TSP-mediated adhesion of sickle erythrocytes to HUVEC. These data imply that cell surface HS-mediated mechanisms play a key role in TSP-mediated sickle erythrocyte adhesion to endothelium, and heparin may be of use for inhibition of this adhesion. PMID- 9989247 TI - Identification of macrophage migration inhibitory factor (MIF) in rat peripheral nerves: its possible involvement in nerve regeneration. AB - Macrophage migration inhibitory factor (MIF) is known as a pluripotent immunoregulatory cytokine involved in T-cell activation and inflammatory responses; however, no study on this protein in the peripheral nervous systems has been carried out. We here demonstrated for the first time expression of MIF mRNA and MIF protein in rat sciatic nerves by reverse transcription-polymerase chain reaction, Western blotting, and immunohistochemistry. Immunohistochemical analysis revealed positive staining of MIF, which was largely observed in Schwann cells. Furthermore, we examined MIF mRNA expression in the sciatic nerves by Northern blot analysis in the case of nerve transection. In both proximal and distal segments, the level of MIF mRNA started to increase 12 h after the nerve transection. The level remained high from 24 h up to day 7 after the injury. During the period from days 14 to 21, MIF mRNA sharply decreased to the pre transection level. In immunohistochemistry, positive staining of MIF was largely observed in axons as well as non-neuronal cells in proximal segments at day 4 after transection. In the distal segments, contrastingly, endoneurial fibroblasts or Schwann cells migrating into neuronal fibers showed positive staining with Wallerian degeneration. Although the precise functions of MIF in the peripheral nerves remain to be elucidated, the present results could represent a major departure from the current state of knowledge, revealing a novel function in the degenerative-regenerative process. PMID- 9989248 TI - Normalization of glucose entry under the high glucose condition by phlorizin attenuates the high glucose-induced morphological and functional changes of cultured bovine retinal pericytes. AB - We previously reported that sodium-dependent glucose uptake is present in bovine retinal pericytes and that phlorizin normalizes its glucose consumption under high glucose conditions. To clarify the effect of phlorizin on morphological and functional change of retinal pericytes under high glucose conditions, retinal pericytes were incubated in media with 5 mM glucose, 30 mM glucose, and 30 mM glucose plus 0.2 mM phlorizin for 7 days. The diameter of cells in the concentrations of glucose more than 10 mM were significantly larger than those in 5 mM glucose and 30 mM glucose plus phlorizin. Glucose, sorbitol and fructose contents of the cells in 30 mM glucose were significantly increased compared with those in 5 mM glucose, and were normalized by phlorizin. Thymidine uptake in the concentrations of glucose more than 20 mM was significantly decreased compared with that in 5 mM glucose. Myoinositol uptake, and DNA in 30 mM glucose were significantly reduced, and were normalized with phlorizin. Myoinositol content in 30 mM glucose was the same as that in 5 mM glucose, but was significantly decreased by phlorizin. The ratios of glucose to sorbitol or fructose in 30 mM glucose were significantly decreased, compared with those in 5 mM glucose and 30 mM glucose plus phlorizin. Therefore, the cellular enlargement and decreased DNA synthesis in cultured bovine retinal pericytes with abnormal glucose metabolism under high glucose conditions are attenuated by phlorizin, independent of the cellular myoinositol content. PMID- 9989249 TI - Proteasome participates in the alteration of signal transduction in T and B lymphocytes following trauma-hemorrhage. AB - Proteasomes are essential components of the cellular protein degradation machinery. They are nonlysosomal and their participation is critical for (1) the removal of short lived proteins involved in metabolic regulation and cell proliferation, (2) the control of the activities of regulators involved in gene transcription, such as nuclear factor-kappa B (NF-kappa B) and signal transducer and activator of transcription (STAT1), and (3) processing of antigenic peptides for MHC class I presentation. Trauma-hemorrhage induces profound immunosuppression which is characterized by reduced splenocyte proliferation, interleukin (IL)-2 and interferon (IFN)-gamma productive capacity, increased activation of transcription factors NF-kappa B and STAT1 in splenic T lymphocytes, reduced macrophage antigen presentation capacity and inordinate release of proinflammatory cytokines, such as IL-6 and tumor necrosis factor alpha. Furthermore, it appears that the activity of several regulatory proteins involved in immune function is altered by trauma-hemorrhage. Since proteasomes are involved in regulation and removal of regulatory proteins, we hypothesized that trauma-hemorrhage alters proteasomal activity in splenic lymphocytes. The data showed that activities of 26s proteasome from CD3+CD4+ and CD3+CD8+ splenic T lymphocytes were enhanced following trauma-hemorrhage which was associated with increased expression of NF-kappa B and STAT1. On the other hand, trauma hemorrhage attenuated the activity of 26s proteasome from splenic B lymphocytes which was restored upon IFN-gamma stimulation and correlated with increased expression of NF-kappa B. These studies indicate a potential role for proteasomes in the regulation of signal transduction in splenic T and B lymphocytes following trauma-hemorrhage, and also suggest them as potential therapeutic targets for attenuation of immune suppression associated with this form of injury. PMID- 9989250 TI - Age-dependent ultrastructural alterations and biochemical response of rat skeletal muscle after hypoxic or hyperoxic treatments. AB - This work deals with the antioxidant enzymatic response and the ultrastructural aspects of the skeletal muscle of young and aged rats kept under hypoxic or hyperoxic normobaric conditions. It is in fact well known that the supply of oxygen at concentrations higher or lower than those occurring under normal conditions can promote oxidative processes that can cause tissue damage. The enzymes investigated were both those directly involved in reactive oxygen species (ROS) scavenging (superoxide dismutase, catalase and selenium-dependent glutathione peroxidase), and those challenged with the detoxication of cytotoxic compounds produced by the action of ROS on biological molecules (glutathione transferase, glyoxalase I, glutathione reductase), in order to obtain a comparative view of the defence strategies used with respect to aging. Our results support the hypothesis that one of the major contributors to the aging process is the oxidative damage produced at least in part by an impairment of the antioxidant enzymatic system. This makes the aged organism particularly susceptible to oxidative stress injury and to the related degenerative diseases, especially in those tissues with high demand for oxidative metabolism. PMID- 9989251 TI - Model multiple antigenic and homopolymeric peptides from non-repetitive sequences of malaria merozoite proteins elicit biologically irrelevant antibodies. AB - Three model peptides containing B-epitopes from conserved, non-repetitive regions of the merozoite surface antigens, MSA2 and MSA1, and the erythrocyte binding protein EBP of Plasmodium falciparum were synthesised. The peptides incorporated GPG spacers and C residues at the N and C termini, and were polymerised by oxidation to form cystine bridges. Multiple copies of essentially the same peptide sequences were also synthesised on a branching lysyl matrix to form a tetrameric multiple antigen peptide. Rabbits were immunised with the polymerised and multiple antigen peptides, in alum followed by Freund's adjuvant, and the antibody responses examined by IFA and ELISA. Reproducible antibody responses were obtained against the MSA1 and EBP but not MSA2 peptides. IgG antibody levels detected by ELISA after three injections of antigen in alum, increased significantly after further immunisation in Freund's adjuvant. IgG levels were largely maintained for at least 23 weeks after the final immunisation. IgM antibodies, generally detectable only after immunisation in Freund's adjuvant, were absent 23 weeks later. Antibody titres against the native protein on fixed parasites, assayed by IFA, were three to five orders of magnitude lower than the corresponding ELISA titres against the peptides. Antibody-dependent inhibition of P. falciparum growth in vitro could not be demonstrated with the immune rabbit sera. The MSA1 and EBP peptides elicited cross-reactive antibodies. The results suggest that the selected non-repetitive sequences are conformationally constrained in the native proteins and only a small proportion of the anti peptide antibodies bind to the native proteins. The significance of the findings for the development of peptide vaccines and the use of peptides in immunoassays is discussed. PMID- 9989252 TI - Hydrophobic lung surfactant proteins B and C remain associated with surface film during dynamic cyclic area changes. AB - The biophysical activity of lung surfactant depends, to a large extent, on the presence of the hydrophobic surfactant proteins B (SP-B) and C (SP-C). The role of these proteins in lipid adsorption and lipid squeeze-out under dynamic conditions simulating breathing is not yet clear. Therefore, the aim of this study was to investigate the interaction of spread hydrophobic surfactant proteins with phospholipids in a captive-bubble surfactometer during rapid cyclic area changes (6 cycles/min). We found that SP-B and SP-C facilitated the rapid transport of lipids into the air-water interface in a concentration-dependent manner (threshold concentration > or = 0.05:0.5 mol% SP-B/SP-C). Successive rapid cyclic area changes did not affect the concentration-dependent lipid adsorption process, suggesting that SP-B and SP-C remained associated with the surface film. PMID- 9989253 TI - Effect of D-ribose on purine synthesis and neurological symptoms in a patient with adenylosuccinase deficiency. AB - Oral supplementation of 10 mmol/kg/day of D-ribose to a patient with an inherited deficit of adenylosuccinase, severe psychomotor retardation, and epilepsy caused a marked increase in plasma concentration and urinary excretion of urate, while minor changes in succinylpurine levels were observed. D-Ribose administration was accompanied by a slight improvement of behaviour and a progressive reduction of seizure frequency, which increased dramatically upon two attempts to withdraw the drug. Substitution of D-ribose with an equivalent amount of D-glucose did not result in an increase of seizure frequency. PMID- 9989254 TI - A systematic approach to evaluate the modification of lens proteins by glycation induced crosslinking. AB - To systematically evaluate the modification of lens proteins by aldose and dicarbonyl sugars during the glycation process, the sugar-dependent incorporation of Lys and Arg, SDS-PAGE profile, amino acid analysis, and fluorophore formation (excitation 370 nm/emission 440 nm) were determined. Reaction mixtures with glycolaldehyde, glyceraldehyde, threose and 3-deoxythreosone showed the greatest extent of Lys crosslinking and fluorescence formation. An increase in fluorescence intensity, but a decrease in Lys and Arg crosslinking, was found with glyoxal, methylglyoxal, hydroxypyruvaldehyde and threosone. In addition glyoxal, methylglyoxal and hydroxypyruvaldehyde caused the specific loss of Arg residues in lens proteins. Reaction mixtures with xylose, xylosone, glucose, glucosone and 3-deoxyglucosone exhibited the least protein modifications; however, incubation with 3-deoxyxylosone resulted in extensive loss of Lys and Arg residues, a higher extent of Lys or Arg crosslinking and significant fluorophore formation. Each sugar exhibited unique characteristics in the modification of lens proteins by glycation. To validly compare the protein modifications occurring during glycation reactions, a systematic approach was employed to evaluate the potential role of aldose and dicarbonyl sugars in protein modification. PMID- 9989255 TI - In vitro cytotoxic effect of wheat gliadin-derived peptides on the Caco-2 intestinal cell line is associated with intracellular oxidative imbalance: implications for coeliac disease. AB - Coeliac disease (CD) is an inflammatory disorder of the upper small intestine in which gluten acts as an essential factor in its pathogenesis. Although it is generally accepted that cereal protein activation of the immune system is involved in CD progression, a non-immunomediated cytotoxic activity of gliadin derived peptides on the jejunal/duodenal tract cannot be excluded. In this work, considering that (a) little has been reported about the intracellular metabolic events associated with gliadin toxicity, and (b) an important role for free radicals in a number of gastrointestinal disease has been demonstrated, we investigated the in vitro effects of gliadin-derived peptides on redox metabolism of Caco-2 intestinal cells during a kinetic study in which cells were exposed to peptic-tryptic digest of bread wheat up to 48 h. We found that the antiproliferative effects displayed by gliadin exposure was associated with intracellular oxidative imbalance, characterised by an increased presence of lipid peroxides, an augmented oxidised (GSSG)/reduced (GSH) glutathione ratio and a loss in protein-bound sulfhydryl groups. Significant structural perturbations of the cell plasma membrane were also detected. Additional experiments performed by using the specific GSH-depleting agent buthionine sulfoximine provide evidence that the extent of gliadin-induced cell growth arrest critically depends upon the 'basal' redox profile of the enterocytes. On the whole, these findings seem to suggest that, besides the adoption of a strictly gluten-free diet, the possibility for an adjuvant therapy with antioxidants may be considered for CD patients. PMID- 9989256 TI - Targeted disruption of the mouse ferrochelatase gene producing an exon 10 deletion. AB - Protoporphyria is a disease characterized by a deficiency in ferrochelatase, the terminal enzyme in the heme biosynthetic pathway, which catalyzes the chelation of iron and protoporphyrin to form heme. Clinical symptoms arise from an accumulation of protoporphyrin behind the partial enzyme block and include photosensitivity and sometimes hepatobiliary disease. Protoporphyria is described as an dominant disease, yet patients exhibit decreased ferrochelatase activities of 15-30% of normal, not 50% as might be expected. Missense, nonsense, and splicing mutations have been identified in ferrochelatase cDNA from protoporphyric patients. In this study we introduce an exon 10 deletion, an analogous mutation to that described in some protoporphyric patients, into the mouse embryonic stem (ES) cell genome via homologous recombination. Targeted ES cells were confirmed by Southern blot analysis. Expression of wild-type and exon 10-deleted mRNA was demonstrated by reverse transcriptase-polymerase chain reaction (RT-PCR) and cDNA sequencing. Ferrochelatase levels were analyzed by immunoblotting. Ferrochelatase activity was measured by the chelation of zinc and mesoporphyrin, and by the decrease in protoporphyrin accumulation after adding delta-aminolevulinic acid. In the exon 10 +/- ES cells there is expression of both wild-type and exon 10-deleted mRNA, a 50% decrease in cross-reactive material with an anti-ferrochelatase antibody, and an approximate 50% decrease in ferrochelatase activity compared to wild-type ES cells. Therefore, an exon 10 deletion alone is insufficient to decrease ferrochelatase activity to the levels in protoporphyric patients. This suggests that requirement of an additional mutation to decrease the expression of the wild-type allele. PMID- 9989257 TI - Osmolyte contents of cultured astrocytes grown in hypoosmotic medium. AB - Primary rat cerebral astrocyte cultures were grown for 2 weeks in isoosmotic medium (305 mosmol) and then placed in similar medium with a reduced NaCl concentration. During the first hour of growth in this moderately hypoosmotic medium (240 mosmol), the cells lose 88% of their taurine contents, 62% of their alanine contents, and 54% of their aspartate contents while regaining normal volume. Loss of these amino acids accounts for 43% of observed volume regulation. Contents of these amino acids remain decreased during 24 h of growth in hypoosmotic medium. In contrast, potassium, glutamate, glutamine, and asparagine contents are not changed, relative to cells in isoosmotic medium, at time points between 1 h and 24 h of hypoosmotic exposure. The data suggest astrocytes contribute to net loss of amino acids, but not potassium, from brains exposed to hypoosmotic conditions in situ. PMID- 9989258 TI - Higher cholesterol in human LDL is associated with the increase of oxidation susceptibility and the decrease of antioxidant defence: experimental and simulation data. AB - Increased low-density lipoprotein (LDL) cholesterol is a recognized risk factor for atherosclerosis. There is also strong evidence that oxidatively modified LDL initiates the development of this pathological process and the administration of antioxidants might have a protective effect. However, the appropriate trials did not provide completely consistent results. We found in this study that the oxidation kinetics and also the antioxidant effectiveness are different depending on the cholesterol content in LDL. Higher cholesterol in LDL causes an acceleration of its oxidation as well as an increase of resistance to the antioxidative effect of ascorbic acid. In searching for a theoretical background of this dual impact of cholesterol in LDL, computer simulation of LDL oxidation was used. It was found that the pre-existing level of lipid hydroperoxides together with the total amount of oxidizable lipid substrate associated with the cholesterol level in LDL were satisfactory prerequisites for a best fit to the experimental data. In conclusion, this study provides at least a partial explanation for some failures to arrest, by administration of antioxidants, the progression of atherosclerosis in animal and human hypercholesterolemia. PMID- 9989260 TI - Receptors for oxidized low density lipoprotein. AB - An increasing body of evidence indicates that oxidized low density lipoprotein (LDL) is involved in the pathogenesis of atherosclerosis. One of the first biologic actions of oxidized LDL to be identified in vitro was its ability to interact with the 'acetyl LDL receptor' discovered by Goldstein and Brown. Over the past decade, considerable progress has been made in identifying and characterizing cell-surface receptors for oxidized LDL. Most of these receptors are thought to be multifunctional because they interact with several structurally different ligands, and accordingly have been termed 'scavenger receptors'. The objective of this article is to review the most important publications dealing with structure, ligand specificity, regulation, and function of scavenger receptors. PMID- 9989259 TI - The ether lipid trail: a historical perspective. PMID- 9989261 TI - Characterization of recombinant guinea pig alkyl-dihydroxyacetonephosphate synthase expressed in Escherichia coli. Kinetics, chemical modification and mutagenesis. AB - A recombinant form of guinea pig alkyl-dihydroxyacetonephosphate synthase, a key enzyme in the biosynthesis of ether phospholipids, was characterized. Kinetic analysis yielded evidence that the enzyme operates by a ping-pong rather than a sequential mechanism. Enzyme activity was irreversibly inhibited by N ethylmaleimide, p-bromophenacylbromide and 2,4-dinitrofluorobenzene. The enzyme could be protected against the inactivation by either of these three compounds by the presence of saturating amounts of the substrate palmitoyl dihydroxyacetonephosphate. The rate of inactivation of the enzyme by p bromophenacylbromide was strongly pH dependent and the highest at alkaline conditions. Collectively, these results are indicative of cysteine, histidine and lysine residues, respectively, at or close to the active site. The divalent cations Mg2+, Zn2+ and Mn2+ were found to be inhibitors of enzymatic activity, whereas Ca2+ had no effect. Mutational analysis showed that histidine 617 is an essential amino acid for enzymatic activity: replacement of this residue by alanine resulted in complete loss of enzymatic activity. A recombinant enzyme with the C-terminal five amino acids deleted was shown to be inactive, indicating an important role of the C-terminus for catalytic activity. PMID- 9989262 TI - The physiological role of sterol regulatory element-binding protein-2 in cultured human cells. AB - To clarify the role of the sterol regulatory element-binding protein-2 (SREBP-2), we established cell lines in which human SREBP-2(1-481) could be induced by isopropyl-beta-D-thiogalactopyranoside (IPTG). The range of IPTG-induced changes in SREBP-2(1-481) levels in '23-11' cells, one of these cell lines, was almost the same as that of sterol-induced changes in the levels of mature SREBP-2, indicating that IPTG was able to regulate the expression of SREBP-2(1-481) within the normal physiological range in this cell line. Sterols regulate the expression of the LDL receptor, HMG-CoA reductase, squalene synthase and fatty acid synthase in 23-11 cells as they also do in the parental cell line HeLa S3. IPTG increased mRNA levels of the LDL receptor and HMG-CoA reductase but not squalene synthase both in the presence or absence of excess sterols. Fatty acid synthase mRNA was increased 2 h after the IPTG addition in the absence of excess sterol (10% FBS), but was slightly increased 6 h after the IPTG addition in the presence of excess sterols. In the absence of excess sterols, both SREBP-2(1-481) and endogenous mature SREBP-2 exist in the nucleus. This suggests that an increased amount of SREBP-2 over the normal physiological range is required for the regulation of fatty acid synthase. IPTG increased both the surface binding of 125I-LDL and cholesterol biosynthesis from [14C]acetate significantly in a similar time course. In contrast, fatty acid biosynthesis from [14C]acetate was almost unchanged by IPTG during the same incubation period. These results suggest that physiological amounts of SREBP-2 play a key role in the regulation of cholesterol but not fatty acid metabolism. PMID- 9989263 TI - Phospholipase D1 is located and activated by protein kinase C alpha in the plasma membrane in 3Y1 fibroblast cell. AB - The subcellular location of phospholipase D1 (PLD1) and its activation by protein kinase C alpha (PKC alpha) were examined by subcellular fractionation and by microscopic observation of green fluorescent protein-fused PLD1 (GFP-PLD1) or PKC alpha (GFP-PKC alpha) in fibroblastic 3Y1 cells. Major PLD1 immunoreactivity and PKC alpha-stimulated PLD activity segregated with a plasma membrane marker, even though a significant amount was co-fractionated with markers for endoplasmic reticulum (ER) and Golgi. Upon treatment with phorbol myristate acetate (PMA), PKC alpha translocated from the cytosolic fraction to the membrane fraction to which PLD1 also localized. GFP-PLD1 was found in the plasma membrane as well as a in a perinuclear compartment consistent with ER and Golgi and in other dispersed vesicular structures in the cytoplasm. However, most of GFP-PKC alpha was translocated from the cytosol to the plasma membrane after treatment with PMA. From these results, we concluded that the plasma membrane is the major site of PLD1 activation by PKC alpha in 3Y1 cells. PMID- 9989264 TI - Conjugated linoleic acid activates peroxisome proliferator-activated receptor alpha and beta subtypes but does not induce hepatic peroxisome proliferation in Sprague-Dawley rats. AB - Since conjugated linoleic acid (CLA) has structural and physiological characteristics similar to peroxisome proliferators, we hypothesized that CLA would activate peroxisome proliferator-activated receptor (PPAR). We compared the effects of dietary CLA (0.0, 0.5, 1.0 and 1.5% by weight) with a peroxisome proliferator (0.01% Wy-14,643) in female and male Sprague-Dawley (SD) rats. Dietary CLA had little effect on body weight, liver weight, and hepatic peroxisome proliferation, compared to male rats fed Wy-14,643 diet. Lipid content in livers from rats fed 1.5% CLA and Wy-14,643 diets was increased (P < 0.01) when compared to rats fed control diets regardless of gender. Hepatic acyl-CoA oxidase (ACO) mRNA levels were increased 3-fold in male rats fed 1.5% CLA diet compared to rats fed control diets while Wy-14,643 supported approximately 30 fold ACO mRNA accumulation. A similar response was observed for liver fatty acid binding protein (L-FABP) mRNA. The effect of dietary treatments on hepatic PPAR responsive genes in female rats was weaker than in male rats. The (9Z,11E)-CLA isomer activated PPAR alpha in transfected cells to a similar extent as Wy 14,643, whereas the furan-CLA metabolite was comparable to bezafibrate on activating PPAR beta. These data suggest that while CLA was able to activate PPARs it is not a peroxisome proliferator in SD rats. PMID- 9989265 TI - Hepatic and extrahepatic dehydrogenation/isomerization of 5-cholestene-3 beta,7 alpha-diol: localization of 3 beta-hydroxy-delta 5-C27-steroid dehydrogenase in pig tissues and subcellular fractions. AB - Conversion of 5-cholestene-3 beta,7 alpha-diol (7 alpha-hydroxycholesterol) into 7 alpha-hydroxy-4-cholesten-3-one was studied with microsomes from different pig tissues and with liver subcellular fractions. Dehydrogenase/isomerase activity was efficient in microsomes from liver, ovary and lung, but less efficient in microsomes from adrenal gland and kidney. Microsomes from these tissues, with the exception of lung, were also active in dehydrogenation/isomerization of dehydroepiandrosterone and pregnenolone. Inhibition studies were carried out with trilostane, a competitive inhibitor of 3 beta-hydroxysteroid dehydrogenases active in steroid hormone biosynthesis (C19/C21-dehydrogenases), and a monoclonal antibody raised against a purified hepatic 3 beta-hydroxy-delta 5-C27-steroid dehydrogenase. The results showed that the C27-dehydrogenase activity in the tissues was not dependent on the C19/C21 dehydrogenases, but was dependent on the 3 beta-hydroxy-delta 5-C27-steroid dehydrogenase. Liver mitochondria, cytosol and peroxisomes lacked dehydrogenase/isomerase activity towards 7 alpha hydroxycholesterol when microsomal contamination was taken into account. Immunoblotting experiments with monoclonal antibodies raised against the 3 beta hydroxy-delta 5-C27-steroid dehydrogenase showed immunoreactivity only with protein in liver microsomes. Immunohistochemical studies showed localization of the 3 beta-hydroxy-delta 5-C27-steroid dehydrogenase in the bile duct epithelium. It is concluded that 7 alpha-hydroxycholesterol is converted into 7 alpha-hydroxy 4-cholesten-3-one by the microsomal 3 beta-hydroxy-delta 5-C27-steroid dehydrogenase in liver and extrahepatic tissues. PMID- 9989266 TI - In vivo stimulation of 12(S)-lipoxygenase in the rat skin by bradykinin and platelet activating factor: formation of 12(S)-HETE and hepoxilins, and actions on vascular permeability. AB - In this study we set out to investigate whether the inflammatory agents, bradykinin (BK) and platelet activating factor (PAF), affect the lipoxygenase pathway in rat skin in vivo and whether the main products so formed may be involved in the inflammatory actions of these agents. In vitro preparations of epidermis were also investigated to determine whether lipoxygenases are stimulated by these agents. We also investigated the actions of arachidonic acid and 12(S)-HPETE as substrates for the lipoxygenases. Our results indicated that 12-lipoxygenase is actively and selectively stimulated in a dose-dependent way in both preparations by the administration of BK and PAF; the main product, 12-HETE, was shown by chiral analysis to be exclusively of the S-configuration, indicating that 12(S)-lipoxygenase was present in the rat skin and was stimulated by these inflammatory agents. Hepoxilins were also formed but to a lesser extent in both in vivo and in vitro preparations. In separate experiments, 12(S)-HETE administered intradermally on its own (40 ng/site), increased vascular permeability as also seen with bradykinin (100 ng/site) and PAF (10 ng/site). However, unlike previously observed with hepoxilin A3 administration, 12(S)-HETE did not stimulate the action of BK on vascular permeability, suggesting that the two compounds may have different mechanisms of action to enhance inflammation. These observations suggest that the vascular permeability and plasma extravasation observed with both inflammatory agents (BK and PAF) may be mediated at least in part through the activation of 12(S)-lipoxygenase, resulting in enhanced formation of 12(S)-HETE which causes acute inflammation. PMID- 9989267 TI - Lysosomal phospholipase activity is decreased in mucolipidosis II and III fibroblasts. AB - Mucolipidosis (ML) II and III are rare autosomal recessively inherited diseases characterized by deficiency of multiple lysosomal enzymes and, as a result, a generalized storage of macromolecules in lysosomes of cells of mesenchymal origin. In ML II and ML III fibroblasts, most, but not all, newly synthesized lysosomal enzymes are secreted into the medium instead of being targeted correctly to lysosomes. Defects in the enzyme UDP-N-acetylglucosamine:lysosomal enzyme N-acetylglucosamine-1-phosphotransferase underlie this effect. It is unknown how lysosomal phospholipases are targeted to the lysosomes of fibroblasts. In the present study lysosomal phospholipase activity was determined in delipidated fibroblast homogenates and plasma from ML II and ML III patients and controls using a [3H]choline-labeled phosphatidylcholine. After incubation, residual phosphatidylcholine and its labeled degradation products (lysophosphatidylcholine, glycerophosphorylcholine and choline phosphate) were quantified. We found that ML II and ML III fibroblasts are deficient in lysosomal phospholipase A and C activity. These enzymes were present in elevated amounts in plasma of ML II and ML III patients. These data indicate that phospholipases, like most other lysosomal enzymes in these diseases, are secreted into the blood instead of being targeted specifically to lysosomes. Thus, the mannose-6 phosphate receptor pathway is needed for proper delivery of lysosomal phospholipases to lysosomes. We also found that production of labeled choline phosphate was mainly due to the activity of acid sphingomyelinase instead of phospholipase C under the assay conditions used. Other active lipolytic enzymes were phospholipase A and lysophospholipase. No evidence for phospholipase D activity was found. PMID- 9989268 TI - Validation of the peroxidative indicators, cis-parinaric acid and parinaroyl phospholipids, in a model system and cultured cardiac myocytes. AB - cis-Parinaric acid is increasingly being used in eukaryotic cells as a very sensitive marker for the initial stages of lipid peroxidation. Despite the increased application of this probe, no extensive validation, especially in cellular systems, has been performed. cis-Parinaric acid can either be inserted freely into biomembranes or incorporated (bio)synthetically into lipids (parinaroyl-lipid). Therefore, a direct comparison was made between the peroxidative behaviour of the two parinaroyl probes and the endogenous polyunsaturated fatty acids arachidonic and linoleic acid, in both an artificial lipidic system and in cultured neonatal rat heart cells. Three different radical generating systems were used, i.e., hydrogen peroxide, cumene hydroperoxide and the thermo-labile 2,2'-azobis(2-amidinopropane hydrochloride) (AAPH). The data demonstrate that the peroxidation rate of cis-parinaric acid is higher than that of the parinaroyl, arachidonoyl and linoleoyl lipids. The latter three displayed comparable peroxidation rates, showing that the peroxidative decay of parinaroyl lipid is a good marker for the degradation of endogenous polyunsaturated fatty acids. Experimental results using the freely inserted cis-parinaric acid could potentially lead to an overestimation of the inflicted damage and should be interpreted with care. In addition, a comparison was made with the measurement of conjugated dienes and malon dialdehyde as thiobarbituric acid reactive substances. The results demonstrate that measurement of conjugated dienes and malon dialdehyde only provide information on peroxidative processes in vitro, but are not suitable for in-depth studies in cultured cells. In contrast, the use of the parinaroyl probes is a suitable, straightforward, sensitive and reproducible method for detecting the initial stages of lipid peroxidation in living cells. PMID- 9989269 TI - The interfacial pressure is an important parameter for the rate of phospholipase D catalyzed reactions in emulsion systems. AB - Phospholipase D (PLD) is widely used for the transformation of phospholipids, which is preferably performed in aqueous-organic emulsion systems. The influence of the organic solvent on the reaction rates has been studied on the hydrolysis of phosphatidylcholine (PC) and its transesterification with glycerol by two types of PLD (cabbage and Streptomyces sp.). The initial rates determined by quantitative HPTLC show great differences in dependence on the solvent used with a similar tendency for both reactions and both PLDs. Since the polymorphism of the PC aggregates was assumed to be responsible for these effects, the critical concentration of micelle formation, the size of the aggregates, the water content of the organic phase, and the interfacial tension were determined in the different reaction systems. As result the interfacial pressure in the reaction systems influencing the package density of the PC aggregates is suggested to regulate the enzymatic activity. PMID- 9989270 TI - Identification of a silencing element in the chicken lipoprotein lipase gene promoter: characterization of the silencer-binding protein and delineation of its target nucleotide sequence. AB - Lipoprotein lipase (LPL) hydrolyzes triglycerides in chylomicrons and very low density lipoproteins (VLDL) and plays a central role in lipid metabolism. It is regulated tissue-specifically. By deletion analysis, a negative regulatory element was identified in the chicken LPL gene promoter at base pairs (bp) -263 to -241. This sequence contained two palindromic halves with a three nucleotide spacer. Either half was sufficient for full inhibitory function. A protein complex bound specifically to this element and a high correlation was found between binding of the complex and inhibition of transcription. Its molecular mass, evaluated by native gel electrophoresis and Ferguson plot analysis, was 120 kDa. UV cross-linking followed by SDS-PAGE revealed two protein subunits of 48 kDa and 44 kDa, respectively. This inhibitory protein complex may contribute to the tissue-specific regulation of LPL gene transcription. It was much more abundant in liver than in adipose tissue and heart. Our data showed that this negative element inhibited transcription even when placed at an upstream location (-666), but failed to function in the herpes simplex virus thymidine kinase promoter, indicating that it acted in conjunction with other element(s) in the chicken LPL gene to inhibit transcription. PMID- 9989271 TI - Identification of three novel cDNAs for human phosphatidylethanolamine N methyltransferase and localization of the human gene on chromosome 17p11.2. AB - Phosphatidylethanolamine is converted to phosphatidylcholine in mammalian liver by the enzyme phosphatidylethanolamine N-methyltransferase (PEMT). A form of the enzyme (PEMT2) has been isolated from rat liver, the cDNA cloned and expressed and the murine gene has been characterized and disrupted. Several lines of evidence suggested that PEMT2 might have a role in hepatocyte proliferation and liver cancer. Hence, we decided to investigate the human form of the enzyme. Unexpectedly, we cloned and expressed three novel human cDNAs encoding PEMT2. These forms differ from each other in the 5'-region with the point of divergence being 15 nucleotides upstream of the putative translation initiation codon. The remainder of the three cDNAs was identical. Expression of the coding region of the cDNAs in McArdle rat hepatoma cells resulted in three stable cell lines that showed a 27- to 115-fold elevation of PEMT activity compared to vector transfected control cell lines. Screening of somatic cell hybrid panels, radiation hybrid panel mapping and fluorescent in situ hybridization mapping localized the human gene for PEMT2 to chromosome 17p11.2. The identification of three different human cDNAs for PEMT2 suggests that understanding the function of PEMT2 will be more complicated than anticipated. PMID- 9989272 TI - Isolation and characterization of two distinct forms of liver fatty acid binding protein from the rat. AB - Liver fatty acid binding protein (L-FABP) appears to contain several different forms that may result from post-translational modification or bound ligand. To further assess this possibility, L-FABP was purified from rat liver homogenate and two putative isoforms separated using a sulfonyl column, a strong cation exchange resin. Fraction I eluted at 0.2 M NaCl, had a pI of 7.59, and following a final size exclusion step contained > 98% L-FABP. Fraction II eluted at 1.0 M NaCl, had a pI of 7.59, and following a final size exclusion step contained > 99% L-FABP. Both fractions contained approx. 0.15 moles of endogenous bound fatty acid per mole of protein, while L-FABP not subjected to the cation exchange step contained 0.75 moles of fatty acid per mole of protein. Fractions I and II had a greater proportion of saturated and monounsaturated fatty acids with a large reduction in polyunsaturated fatty acids compared to L-FABP not fractionated by cation exchange. Mass spectral analysis indicated the molecular mass of Fraction I was 14,315.02 +/- 0.35 Da and Fraction II was 14,315.86 +/- 0.34 Da. The peptide map for each fraction was determined by limited digestion of each fraction with either trypsin, Asp-N, or chymotrypsin to yield overlapping peptide fragments. Mass spectral analysis of these digests indicated the two proteins had identical amino acid fragments and that Cys69 was reduced and there were no Asn to Asp exchanges. Hence, these two forms of L-FABP were not isoforms and were not the result of differences in bound fatty acid. It is proposed that these two distinct forms of rat L-FABP were structural conformers based on two alternative folding pathways. PMID- 9989273 TI - A novel phosphoglycolipid archaetidyl(glucosyl)inositol with two sesterterpanyl chains from the aerobic hyperthermophilic archaeon Aeropyrum pernix K1. AB - The structures of two novel polar lipids (AGI and AI) of an aerobic hyperthermophilic archaeon, Aeropyrum pernix, were elucidated. AGI and AI were the only two major lipids and accounted for 91 mol% and 9 mol%, respectively, of total polar lipids of this organism. The core lipid of A. pernix total lipids consisted solely of 2,3-di-O-sesterterpanyl-sn-glycerol (C25,25-archaeol). The molecular weights of the free acid forms of AGI and AI were shown by FAB-mass spectrometry to be 1196 and 1034, respectively. AI was completely hydrolyzed by phosphatidylinositol-specific phospholipase C, while AGI was not hydrolyzed at all under the same condition for the hydrolysis of AI. The molar ratio of phosphate, myo-inositol, and glucose in AGI was 1.0:0.97:0.95. The positions of linkages between myo-inositol and glucose, and between myo-inositol and phosphate in AGI were determined by NMR analyses of intact AGI and glucosylinositol prepared from AGI. Finally, it was concluded that the structures of AGI and AI were 2,3-di-O-sesterterpanyl-sn-glycerol-1-phospho-1'-(2'-O-alpha-D-glu cosyl)- myo-inositol (C25,25-archaetidyl(glucosyl)inositol) and 2,3-di-O-sesterterpanyl sn-glycerol-1-phospho-myo-inositol (C25,25-archaetidylinositol), respectively. This is the first example that a core lipid of whole polar lipids is composed of only one species C25,25-archaeol in one organism and that glucosylinositol is found in a polar lipid as a polar head group. PMID- 9989274 TI - Phosphatidylinositol synthesis in mycobacteria. AB - The metabolism and synthesis of an important mycobacterial lipid component, phosphatidylinositol (PI), and its metabolites, was studied in Mycobacterium smegmatis and M. smegmatis subcellular fractions. Little is known about the synthesis of PI in prokaryotic cells. Only a cell wall fraction (P60) in M. smegmatis was shown to possess PI synthase activity. Product was identified as PI by migration on TLC, treatment with phospholipase C and ion exchange chromatography. PI was the only major product (92.3%) when both cells and P60 fraction were labeled with [3H]inositol. Also, a neutral lipid inositol containing product (4.1% of the total label) was identified in the P60 preparations. Strangely, PI synthase substrates, CDP-dipalmitoyl-DAG and CDP-NBD DAG, added to the assay did not stimulate [3H]PI and NBD-PI yield by M. smegmatis. At the same time, addition of both substrates to rat liver and Saccharomyces cerevisiae PI synthase assays resulted in an increase in the product yield. Upon addition of CHAPS to the mycobacterial PI synthase assay, both substrates were utilized in a dose-dependent manner for the synthesis of NBD PI and [3H]PI. These results demonstrate a strict substrate specificity of mycobacterial PI synthase toward endogenous substrates. K(m) of the enzyme toward inositol was shown to be 25 microM; Mg2+ stimulated the enzyme to a greater degree than Mn2+. Structural analogs of myo-inositol, epi-inositol and scyllo inositol and Zn2+ were shown to be more potent inhibitors of mycobacterial PI synthase than of mammalian analogs. Lack of sequence homology with mammalian PI synthases, different kinetic characteristics, existence of selective inhibitors and an important physiological role in mycobacteria, suggest that PI synthase may be a good potential target for antituberculosis therapy. PMID- 9989275 TI - Intestinal synthesis and lymphatic secretion of apolipoprotein A-IV after cessation of duodenal fat infusion: mediation by bile. AB - We tested whether secretion of apolipoprotein (apo) A-IV depends upon intestinal triglyceride (TG) transport by comparing output kinetics of TG and apo A-IV during and after duodenal lipid infusion in lymph-fistula rats. Lipid infusion (triolein, 40 mumol/h, 8 h) produced increases in lymphatic TG and apo A-IV output. After 8 h, triolein infusate was replaced with glucose-saline; TG output returned to basal levels 4-5 h later. However, apo A-IV output continued at significantly elevated levels until 20 h after the start of the experiment. Bile diversion blocked this continued output of A-IV during the post-lipid period, and resulted in basal TG output that was 75% lower than in bile-intact rats. Return of bile or low-dose triolein infusion (5 mumol/h) into the intestine reversed these effects. There were no differences in hepatic synthesis or filtration of plasma A-IV into lymph between bile-intact and bile-diverted groups. Intestinal A IV synthesis was elevated in both groups even during the post-lipid period. The results support the hypothesis that intestinal triglyceride transport drives apo A-IV secretion, and suggest the existence of a bile-dependent, post-translational mechanism for the control of lymphatic apo A-IV output. PMID- 9989276 TI - Eicosanoid biosynthesis in an advanced deuterostomate invertebrate, the sea squirt (Ciona intestinalis). AB - The eicosanoid generating potential of tunic, branchial basket, intestine, ovary and tadpole larvae from the sea squirt, Ciona intestinalis, was examined using a combination of reverse phase high performance liquid chromatography, gas chromatography-mass spectrometry and enzyme immunoassay. All organs examined synthesized the lipoxygenase products 12-hydroxyeicosapentaenoic acid (12-HEPE) and 8-HEPE implying that both 8- and 12-lipoxygenase activity are widely distributed in this species. In addition, tunic and branchial basket generated significant amounts of 8,15-diHEPE and smaller amounts of 8,15 dihydroxyeicosatetraenoic acid (8,15-diHETE), while tunic alone generated small amounts of conjugated tetraene-containing material with a UV chromophore and mass ion characteristic of a lipoxin-like compound. The broad range lipoxygenase inhibitors, esculetin and nordihydroguaiaretic acid, both caused a significant dose dependent inhibition of 12-HEPE and 8,15-diHEPE biosynthesis in tunic, while the specific 5-lipoxygenase inhibitor, REV-5901, and the specific 5-lipoxygenase activating protein inhibitor, MK-866, had no observable effect on the lipoxygenase profile of this tissue. Tunic, branchial basket, intestine and ovary all generated significant amounts of prostaglandin (PG) E and PGF immunoreactive material and smaller amounts of thromboxane B immunoreactive material as measured by enzyme immunoassay. The non-specific cyclooxygenase (COX) inhibitor, indomethacin, the selective COX-1 inhibitors, resveratrol and valerylsalicylate, and the specific COX-2 inhibitors, NS-398, etolodac and DFU (5,5-dimethyl-3-(3 fluorophenyl)-4-(4-methylsulphonyl) phenyl-2(5H)-furanone) all caused a significant dose dependent inhibition of the biosynthesis of PGE immunoreactive material. However, the specific COX-2 inhibitors were most effective, perhaps implying that a COX-2-like enzyme may be present in this species. PMID- 9989277 TI - Reduced lecithin:retinol acyl transferase activity in cultured squamous cell carcinoma lines results in increased substrate-driven retinoic acid synthesis. AB - The uptake and metabolism of retinol was compared in squamous cell carcinoma lines, SCC12b and SCC13, and in normal human keratinocytes (NHK). Long chain fatty acid esters of retinol and 3,4-didehydroretinol were the predominant metabolites formed in both cell types. Lesser amounts of unesterified retinol, 3,4-didehydroretinol, and their respective active acid forms were also observed. Despite a qualitatively similar retinoid composition, there were significant quantitative differences between cell types. Most notable was that SCC formed only about one-fourth the retinoid ester as did normal cells. In parallel with this, unesterified retinol and retinoic acid concentrations in SCC were significantly elevated over those in normal cells. This altered pattern of retinoid metabolites in SCC was found to be due to very low lecithin:retinol acyltransferase (LRAT) activity. SCC exhibited less than one-tenth the LRAT activity of normal cells. Acyl-coenzyme A:retinol acyltransferase (ARAT) and retinyl ester hydrolase activities were not different between cell types. Challenging cells with increasing medium retinol concentrations resulted in dose dependent increases in retinol and retinoic acid within SCC. In contrast, retinol and retinoic acid concentrations in similarly challenged normal cells remained relatively low across a wide retinol concentration range. This was accomplished by the storage of retinol, via LRAT activity, as retinyl ester. Consistent with increased substrate-driven retinoic acid synthesis in SCC, the expression of transglutaminase 1 was suppressed to a greater extent in the SCCs than in NHK, when cells were exposed to equivalent medium concentrations of retinol. The data demonstrate a central role of LRAT in regulating retinoic acid synthesis via its capacity to modulate cellular levels of substrate retinol. PMID- 9989279 TI - Fasting increases tissue uptake and interconversion of plasma unesterified linoleic acid in guinea pigs. AB - A large part of the arachidonic acid (20:4 n-6) pools in some extrahepatic tissues can be formed by local interconversion of linoleic acid (18:2 n-6) taken up as free fatty acid (FFA) from blood in both rats and guinea pigs. This study investigates the rate of uptake and interconversion of unesterified 14C-18:2 by different tissues in fasted guinea pigs. The initial half-life of 14C-18:2 in plasma was 5.8 s. The average concentration of plasma FFA was 551.3 nmol ml-1 and of plasma FFA-18:2 was 67.3 nmol ml-1. The total amount of 20:4 formed in the liver was 1.8 +/- 0.3 nmol min-1, which was lower than that in the gastrointestinal tract (3.1 nmol min-1), bone marrow (6.0 nmol min-1) and lung (2.1 nmol min-1). Due to the fast turnover and higher concentration of plasma FFA 18:2 in the fasting state, the retained 18:2 in tissue lipids was 5.8-25.6-fold higher than that in fed guinea pigs [L. Zhou et al. Biochim. Biophys. Acta 1349 (1997) 197-210]. The total delta 6-desaturase products both in liver and in extrahepatic tissues were also increased, 3.8-fold in liver, 7.2-fold in upper small intestine, 6.0-fold in colon, and 6.5-fold in bone marrow. The increased rate of tissue uptake of FFA during fasting is thus linked to an increased local interconversion of plasma FFA-18:2, which is an important source of 20:4 in some extrahepatic tissue in guinea pigs. PMID- 9989278 TI - Binding of fatty acid ethyl esters to albumin for transport to cells in culture. AB - Fatty acid ethyl esters (FAEE) are non-oxidative products of ethanol metabolism that have been proposed to mediate pathological changes in various organs and tissues resulting from excessive ethanol consumption. Evidence supporting this proposal is scant, however, mainly because of the lack of adequate methods with which to solubilize the highly hydrophobic FAEE in aqueous medium for testing under physiological conditions. In this report we describe a simple and practical method for solubilizing FAEE in aqueous medium by binding them to albumin. We also report that the albumin-bound FAEE are readily taken up by rat alveolar macrophages in culture. The availability of FAEE bound to albumin, their main physiological carrier in vivo, will facilitate the investigation of the role that these metabolites may have in mediating pathological changes associated with excess ethanol consumption. PMID- 9989281 TI - Effects of dietary docosahexaenoic acid on surface molecules involved in T cell proliferation. AB - It is known that n-3 polyunsaturated fatty acids (PUFA) such as docosahexaenoic acid (DHA) suppress immunity as compared with n-6 PUFA such as linoleic acid (LA), but the mechanism involved in this phenomenon is still unclear. The present study was designed to assess the effect of dietary DHA on the surface molecules involved in T cell proliferation. Weanling male C57BL/6 mice were divided into four dietary groups that were fed a 10% fat diet for 4 weeks varying in amounts of DHA and LA. As the dietary DHA concentration increased, the surface expression of CD4 and CD8 on splenic T cells decreased, while that of CD28 increased. The surface expression of CD3, however, was invariable in all dietary groups. DNA synthesis of splenic T cells, induced by CD3 crosslinkage with anti-CD3 epsilon monoclonal antibody in the presence of CD28-mediated costimulation, increased as the DHA concentration was elevated. These observations suggest that diets rich in DHA exert some of their immunomodulatory effects by a downregulation of surface expression of CD4 and CD8 and by an upregulation of CD28-mediated costimulatory signal. PMID- 9989280 TI - Affinities of various mammalian arachidonate lipoxygenases and cyclooxygenases for molecular oxygen as substrate. AB - In an attempt to study affinities for molecular oxygen of mammalian arachidonate oxygenases, which remain unclarified at present, we determined activities of platelet-type 12-lipoxygenase, leukocyte-type 12-lipoxygenase, 5-lipoxygenase, 15 lipoxygenase, cyclooxygenase-1 and cyclooxygenase-2 at various oxygen concentrations. Activities of all the tested enzymes were assessed by oxygenation of radioactive arachidonic acid under hypoxic conditions, and part of the enzymes were also assayed by monitoring oxygen consumption. Their Km values for oxygen ranged between 10 and 26 microM. These results should be considered in investigations of arachidonic acid metabolism in pathophysiological processes associated with hypoxia. PMID- 9989282 TI - The purification and characterization of fatty acid hydroperoxide lyase in sunflower. AB - Two fatty acid hydroperoxide lyases (HPO lyase I and II) were purified to apparent homogeneity from etiolated hypocotyls of sunflower (Helianthus annuus L.) by a combination of ion-exchange, hydrophobic interaction, and gel filtration chromatography. The two HPO lyases were separated during the hydrophobic interaction chromatography step, with HPO lyase I more hydrophilic than HPO lyase II. The estimated M(r) of both native HPO lyases was determined by gel filtration to be 200,000 and SDS-PAGE in the presence of 100 mM dithiothreitol showed that the enzyme was composed of a single 53 kDa peptide, suggesting that the enzyme exists as a tetramer in vivo. HPO lyase was also abundant in the cotyledons and green leaves. HPO lyases I and II from hypocotyl metabolized 13 hydroperoxylinoleic acid and 13-hydroperoxylinolenic acid to the same extent, but the green leaf enzyme was more than ten-fold more active with 13 hydroperoxylinolenic acid than 13-hydroperoxylinoleic acid. A difference spectrum between CO-bound and CO-unbound dithionite-reduced HPO lyase I showed an absorbance maximum at 452 nm, indicating that it was a cytochrome P450-type enzyme. The activities of HPO lyase I and II were significantly inhibited by nordihydroguaiaretic acid, sulfhydryl reagents, and piperonylbutoxide, which is a cytochrome P450 inhibitor. PMID- 9989283 TI - Short-term regulation of carnitine palmitoyltransferase I in cultured rat hepatocytes: spontaneous inactivation and reactivation by fatty acids. AB - Liver carnitine palmitoyltransferase I (CPT I), the rate-limiting enzyme of mitochondrial beta-oxidation, rapidly loses its activity when hepatocytes are put in culture. 3-Thia fatty acids reactivate the enzyme and can increase its activity 3-4-fold in 5-10 min. Normal fatty acids are also able to stimulate CPT I, but to a limited extent, compared to 3-thia fatty acid. This activation does not affect malonyl-CoA sensitivity. CPT I in hepatocytes from both fasted and fasted-carbohydrate refed rats is inactivated and reactivated to a similar extent. Free dodecylthioacetic acid (DTA) is at least as efficient as DTA-CoA as activator. CPT I activity in isolated mitochondria is not influenced by incubation with DTA, suggesting that the regulation of CPT I depends on an extramitochondrial component(s) in the cell. It is concluded that fatty acids activate pre-existing, inactive CPT I without involvement of gene transcription and independently of malonyl-CoA. PMID- 9989284 TI - Evidence for the formation of a novel cyclopentenone isoprostane, 15-A2t isoprostane (8-iso-prostaglandin A2) in vivo. AB - A2/J2-Isoprostanes (IsoPs) are prostaglandin (PG) A2/J2-like compounds that are produced in vivo as dehydration products of D2/E2-IsoPs. One A2-IsoP that should be formed is 15-A2t-IsoP (8-iso-PGA2). Analogous to cyclopentenone PGs, 15-A2t IsoP readily undergoes nucleophilic addition to various biomolecules suggesting the compound is capable of exerting potent bioactivity. However, proof that it is definitively formed in vivo is lacking. Evidence is now presented that 15-A2t IsoP, in fact, is generated in vivo by demonstrating that an endogenous A2-IsoP with a retention time on capillary GC identical with that 15-A2t-IsoP co chromatographs through four high resolving HPLC purification procedures with authentic radiolabeled 15-A2t-IsoP. PMID- 9989285 TI - Low-density lipoprotein activates Jun N-terminal kinase (JNK) in human endothelial cells. AB - We have reported previously that native low-density lipoprotein (LDL) activates c Jun and transcription factor AP-1 in human umbilical vein endothelial cells (HUVEC). The aim of this study was to elucidate the upstream signaling mechanisms mediating LDL activation of c-Jun/AP-1. Using a c-Jun NH2-terminal kinase (JNK) activity assay, we have detected an increase in JNK activity in LDL-exposed HUVEC, which started at 15 min and reached maximum activity after 1-2 h. This JNK activity, increased by LDL, occurred in a dose-dependent fashion starting at a concentration of 80 mg/dl of LDL and reaching maximum activation at a concentration of 160-240 mg/dl. Following cotransfection, the increase of AP-1 driven luciferase activity by LDL was attenuated 54% by a kinase-deficient JNK1. Furthermore, a specific trans-reporting system was utilized to confirm c-Jun activation by upstream signal mechanisms. The results show c-Jun activity increased by 3-fold after LDL exposure when compared with respective controls. In contrast, LDL exposure did not affect the activation of extracellular signal regulated kinase 1 and 2 (ERK1/2), even though phorbol 12-myristate 13-acetate treatment remarkably increased the activity of these kinases. Thus, this study demonstrates, for the first time, that JNK mediates LDL-induced endothelial cell activation. PMID- 9989286 TI - The selective pathway and a high-density lipoprotein receptor (SR-BI) in ovarian granulosa cells of the mouse. AB - We recently reported that rat luteinized ovary tissue and primary cultures of rat ovarian granulosa cells reveal a remarkably tight functional correlation between expressed selective uptake of lipoprotein cholesteryl esters and the expression of an HDL receptor protein, scavenger receptor, class B, type I (SR-BI). In the current study, we examine these same processes in C57 mouse granulosa cells and report a different correlation. Unlike the rat cells, non-hormone stimulated mouse granulosa cells are able to effectively carry out their selective pathway functions and secrete HDL-derived progestins despite low levels of SR-BI and barely detectable levels of SR-BII (an isoform of SR-BI). Once stimulated with trophic hormones or Bt2cAMP, small (30-40%) increases are observed in selective pathway functions, but major (approximately 20-fold) increases are seen in SR-BI and SR-BII expression: thus, relatively little is gained in selective cholesteryl ester uptake by mouse granulosa cells even though SR-BI and SR-BII levels are greatly increased. The importance of the HDL receptor proteins to the selective pathway remains clear, however, since a significant portion of the selective process in both basal and stimulated granulosa cells is inhibitable by the use of blocking antibody. Another surface protein, caveolin, previously reported to co localize with SR-BI in mouse cells shows no change in expression during periods when SR-BI/BII levels are undergoing major shifts. PMID- 9989287 TI - Effect of increased afterload on cardiac lipoprotein lipase and VLDL receptor expression. AB - Fatty acids are a major source of fuel for energy production by myocytes. Lipoprotein lipase (LPL) and very low density lipoprotein (VLDL) receptor are abundantly expressed by the heart and skeletal muscles. LPL and possibly VLDL receptor represent the primary route of access to fatty acids contained in circulating triglyceride-rich lipoproteins. Physical exercise and thyroid hormone, which promote energy consumption, upregulate LPL expression in skeletal muscles. This study tested the hypothesis that increased cardiac workload might modulate myocardial LPL and/or VLDL receptor expressions. Accordingly, cardiac tissue LPL activity, LPL and VLDL receptor proteins and mRNA abundance were studied in Sprague-Dawley rats 4 weeks after induction of severe thoracic aorta constriction or sham operation. Elevation of afterload with thoracic aortic constriction led to a significant cardiomegaly and a marked upregulation of cardiac LPL activity, LPL mRNA and LPL protein abundance, but did not modify VLDL receptor mRNA or protein abundance. Thus, increased cardiac workload in this model results in upregulation of myocardial LPL expression which can enhance fatty acid availability to accommodate the heart's increased energy requirement. PMID- 9989288 TI - Tumor necrosis factor-alpha regulates in vivo expression of the rat UCP family differentially. AB - A family of uncoupling proteins (UCPs), free fatty acid anion transporters, plays a crucial role in energy homeostatic thermoregulation. Tumor necrosis factor alpha (TNF-alpha), a member of the cytokine family, is well known as an endogenous pyrogen. To evaluate the interaction of TNF-alpha with UCPs in thermogenesis, effects of TNF-alpha on rat UCP gene expression were examined in intrascapular brown adipose tissue (BAT), epididymal white adipose tissue (WAT) and soleus muscle (Muscle). Administration of TNF-alpha elevated rectal temperature by 0.7 degree C as well as serum leptin which peaked at 6 h, compared with saline controls. BAT UCP1 mRNA expression was increased by 1.2-fold at 6 h after the TNF-alpha treatment and decreased by 0.8-fold at 16 h after the treatment. In contrast to UCP1 expression in BAT, UCP2 mRNA expressions in BAT, WAT, and Muscle was increased to reach maximum levels of 1.3-, 1.6- and 1.8-fold, respectively, at 16 h after the treatment. UCP3 mRNA in Muscle, but not in BAT or WAT, was exclusively up-regulated by 1.7-fold at 16 h after the treatment. These results indicate that TNF-alpha up-regulates UCP gene expression differentially and tissue dependently, and add novel insights into thermogenesis under conditions of malignancy and inflammation. PMID- 9989289 TI - Output of liver fatty acid-binding protein (L-FABP) in bile. AB - Liver fatty acid-binding protein (L-FABP) is a small cytoplasmic molecule highly expressed in the liver. Since L-FABP exhibits affinities for several biliary components, its presence in bile was explored by Western blotting and competitive ELISA in various mammalian species. A L-FABP-like immunoreactivity was consistently found in both hepatic and gallbladder bile. A close molecular identity between this 14 kDa biliary protein and the purified L-FABP was assessed by immunological analyses and high performance capillary electrophoresis. Pharmacological induction of hepatic L-FABP biosynthesis led to a similar increase in biliary L-FABP levels showing a close relationships between the cytosolic and biliary contents of this protein. Finally, a correlation between the presence of L-FABP in bile and both bile flow and bile acid release was found. These data suggest an output of L-FABP in bile in normal conditions which might be coupled with the physiological release of biliary components. PMID- 9989290 TI - A single in vitro point mutation in the first non-translated exon silences transcription of the human apolipoprotein B gene in HepG2 cells. AB - Hepatic cell-specific expression of the human apolipoprotein B (apoB) gene is controlled by at least four cis-acting elements located within the -128 to +122 promoter region (S.S. Chuang, H.K. Das, Identification of trans-acting factors that interact with cis-acting elements present in the first non-translated exon of the human apolipoprotein B gene, Biochem. Biophys. Res. Commun. 220 (1996) 553 562). Two cis-acting positive elements (-104 to -85; -84 to -60) are located upstream from the start of transcription. A negative element (+20 to +40) and a strong positive element (+43 to +53) are located in the first non-translated exon of the human apolipoprotein B gene. Trans-acting factors BRF-2, BRF-1, BRF-3, and BRF-4 interact with the above four cis-acting elements respectively. In this study, we examine the roles of the upstream positive elements -104 to -85 and -84 to -60 in modulating transcriptional regulation of the apoB gene by downstream elements +20 to +40 and +43 to +53. Using in vitro mutagenesis and transient transfection experiments in HepG2 cells, the cis-acting element -84 to -60 has been found to be absolutely necessary for the function of the upstream element 104 to -85 and downstream elements +20 to +40 and +43 to +53. In vitro mutagenesis of the downstream positive element +43 to +53 and transfection of the mutant promoter constructs in HepG2 cells reveal that nucleotide G at position +51 is essential for the strong positive activity of the element +43 to +53. A single substitution point mutation of nucleotide G to either A or T at position +51 reduces apolipoprotein B gene transcription substantially in HepG2 cells. These results suggest that a single substitution mutation in vivo, of nucleotide G to either A or T at position +51 in the downstream positive promoter element +43 to +53 may potentially cause hypobetalipoproteinemia, a heterozygous from of an autosomal-dominant disorder. PMID- 9989291 TI - Prostaglandin D2 and sleep regulation. AB - Prostaglandin (PG) D2 is recognized as the most potent endogenous sleep-promoting substance whose action mechanism is the best characterized among the various sleep-substances thus far reported. The PGD2 concentration in rat cerebrospinal fluid (CSF) shows a circadian change coupled to the sleep-wake cycle and elevates with an increase in sleep propensity during sleep deprivation. Lipocalin-type PGD synthase is dominantly produced in the arachnoid membrane and choroid plexus of the brain, and is secreted into the CSF to become beta-trace, a major protein component of the CSF. The PGD synthase as well as the PGD2 thus produced circulates in the ventricular system, subarachnoidal space, and extracellular space in the brain system. PGD2 then interacts with DP receptors in the chemosensory region of the ventro-medial surface of the rostral basal forebrain to initiate the signal to promote sleep probably via the activation of adenosine A2A receptive neurons. The activation of DP receptors in the PGD2-sensitive chemosensory region results in activation of a cluster of neurons within the ventrolateral preoptic area, which may promote sleep by inhibiting tuberomammillary nucleus, the source of the ascending histaminergic arousal system. PMID- 9989292 TI - Study on the activation of phospholipases A2 by purinergic agonists in rat submandibular ductal cells. AB - Extracellular ATP and benzoyl-ATP (Bz-ATP) increased the release of [3H]arachidonic acid ([3H]AA) from prelabeled rat submandibular gland (RSMG) ductal cells respectively two- and threefold. Both agonists also increased the release of [3H]AA from acini but at a lower level (+50% and +100% respectively). Carbachol had no significant effect on either cellular population. In ductal cells phorbol myristate acetate, an activator of protein kinase C, slightly increased the basal release of [3H]AA but did not affect the release of [3H]AA in response to ATP. Staurosporine, an inhibitor of protein kinases, inhibited the response to the purines. The removal of calcium from the extracellular medium decreased the response to ATP and Bz-ATP. Only barium could partly substitute for calcium to restore the purinergic response. Zinc inhibited the release of [3H]AA. Permeabilization of the cells with streptolysin O (SLO) activated the calcium independent phospholipase A2 activity (iPLA2). The iPLA2, not the calcium dependent PLA2 (cPLA2), released [3H]oleic acid ([3H]OA) from RSMG ductal cells. It is concluded that RSMG ducts have a higher PLA2 activity when compared to acini. This activity is accounted for by iPLA2 and cPLA2. Both enzymes are activated by P2X agonists by a staurosporine-sensitive mechanism. Cells permeabilized with SLO or membranes from Escherichia coli as a substrate are not good models to study the regulation of these enzymes. In intact RSMG ductal cells the two activities can be distinguished by rather specific inhibitors, by different ionic conditions and also by the fatty acid used to label the cells. PMID- 9989294 TI - [Mycoplasma pneumoniae pneumopathy. 10 cases]. AB - OBJECTIVES: Describe the different features of a common disease: Mycoplasma pneumoniae pneumonia. PATIENTS AND METHODS: The hospital files of 10 consecutive patients with microbiologically proven Mycoplasma pneumoniae pneumonia were reviewed retrospectively. These 10 patients were hospitalized over a 15-month period among 150 patients admitted to the Versailles general hospital for community-acquired pneumonia. We compared our series with data in the literature. RESULTS: Most of the patients with Mycoplasma pneumoniae pneumonia were young apparently healthy adults. A bronchial risk factor (smoking, allergy) was however found in 60% of the patients. The principle symptom was persistent cough (100%), with fever and joint pain, or sometimes headache and signs of ENT involvement. Dyspnea was frequent, related more to associated bronchospasticity than to the severity of the pneumonia. Radiographic findings were quite variable. In one case hemolytic anemia and cold agglutinins suggested the diagnosis. Certain diagnosis was based on positive serology after hospitalization due to the long delay between symptom onset and hospitalization. The prehospital period was characterized by a succession of ineffective empirical antibiotic regimens. In routine practice, macrolides or fluoroquinolones administered for 2 to 3 weeks are the empirical antibiotics of choice. Outcome is generally favorable with rapid clinical and radiological improvement. Antibiotic therapy is not however sufficient alone to achieve improvement in the respiratory impairment: bronchodilators and corticosteroids are necessary to treat the bronchospasticity. CONCLUSION: Despite the benign nature of community-acquired pneumonia due to Mycoplasma pneumoniae, clinical manifestations, particularly bronchial inflammation may have important consequences. PMID- 9989295 TI - [Extracapillary glomerulonephritis with anti-myeloperoxidase antibodies in 2 patients with systemic scleroderma treated with penicillamine D]. AB - BACKGROUND: Side-effects, including autoimmune disorders, are frequent with D penicillamine therapy. Proteinuria is observed in 10% of the patients, often secondary to extramembranous glomerulopathy. Necrotizing extracapillary glomerulonephritis is however exceptional. CASE REPORTS: Two patients with systemic sclerodermia were treated with D-penicillamine for 7 and 14 years. Both developed necrotizing extracapillary glomerulonephritis with anti-myeloperoxidase antibodies (anti-MPO), associated with hemorrhagic alveolitis in one case. Partial regression of the renal failure was obtained after withdrawal of D penicillamine and combination treatment with prednisone and cyclophosphamide. DISCUSSION: Extracapillary glomerulonephritis or a lung-kidney syndrome are frequently associated with anti-MPO antineutrophil cytoplasm antibodies (ANCA). In systemic sclerodermia, the presence of anti-MPO appears to define a group of patients at risk of pauci-immune extracapillary glomerulonephritis or a lung kidney syndrome. In addition, the presence of ANCA in patients with renal failure would suggest extracapillary glomerulonephritis rather than sclerodermic microangiopathy. Development of extracapillary glomerulonephritis with anti-MPO in patients who are taking D-penicillamine suggests that inductor mechanisms other than D-penicillamine are involved in the pathogenesis of these glomerulopathies. PMID- 9989296 TI - [Cannabis-induced arteritis vs. Leo Buerger disease. Nosologic discussion apropos of two new cases]. AB - BACKGROUND: We observed two cases of juvenile endarteritis which might suggest a possible link between Winiwarter-Buerger disease and cannabis-induced endarteritis. CASE REPORTS: Our two patients were young men aged 18 and 20 years. Both developed acute distal ischemia of the lower or upper limbs with arteriographic evidence suggestive of Winiwarter-Buerger disease. Both smoked regularly but not excessively and both used cannabis regularly. In one case, the therapeutic response to withdrawal of cannabis was good. In the second, use of cannabis continued and arterial disease persisted. DISCUSSION: The cause of Winiwarter-Buerger disease remains elusive although smoking is undoubtedly involved in the pathogenic mechanism. Our two cases recall the cannabis-induced endarteritis described in the sixties in Kif smokers in North Africa. The main clinical and radiographical features in this condition are the same as in Winiwarter-Buerger disease. CONCLUSION: Winiwarter-Buerger disease and cannabis induced endarteritis are 2 very similar conditions. The probably rare finding of juvenile endarteritis mimicking thromboangeitis obliterans should, in our opinion, be considered as a secondary and possibly toxic effect of cannabis. PMID- 9989297 TI - [Edema of the lower extremities in a HIV seropositive patient: secondary effect of ritonavir?]. PMID- 9989298 TI - [Carcinomatous meningitis secondary to breast cancer. Spectacular response to hormone therapy]. PMID- 9989299 TI - [Vestibular manifestations revealing acoustic neurinoma with normal hearing]. PMID- 9989300 TI - [Opinion on interferon-ribavirin association in the primary treatment of chronic hepatitis C]. PMID- 9989301 TI - [Bronchial cancer. Consensual attitudes, twilight zones and practical difficulties. International Association for Study on Lung Cancer]. PMID- 9989302 TI - [Coronary insufficiency associated with heart failure. Congress of the American Heart Association, Texas, 8-11 November 1998]. PMID- 9989303 TI - [Eating disorders. Virtual identity and social contagion]. PMID- 9989304 TI - [Eating disorders. Anorexia nervosa in adolescents]. AB - EPIDEMIOLOGICAL DATA: Anorexia nevrosa is mainly observed in young women in the 15-24 year age range. The incidence is 1 to 2% in the general population of female adolescents. The sex ratio is 9 girls for 1 boy. SYMPTOM TRIAD: Three symptoms predominate in anorexia nevrosa: weight loss, anorexia, amenorrhea. Weight loss results from restrictive eating behavior and not from a loss of appetite. CLINICAL DIAGNOSIS: Diagnosis is clinical and confirmed by an analysis of the underlying psychological conflicts which involve difficulty in accepting the female identity and in assuming self-sufficiency outside the family. The clinician should evaluate the quality of the familial environment, particularly the mother-daughter and father-daughter relationship as well as the social environment (school, friends) which is also needed to apprehend the global situation. Physical examination and laboratory tests are aimed at rapidly eliminating any differential diagnosis and to quantify the weight loss and its rate, and identify any nutritional disorders. ETIOLOGY: Anorexia nevrosa is not a truly structured psychopathological disorder but rather a loss of a stable organization of Self, with a highly vulnerable narcissistic element and precarious neurotic defences. CLINICAL COURSE: The risk of poor outcome is very real, sometimes life threatening. The treatment of choice is to implement analytical management as soon as possible, but outside acute episodes. PMID- 9989305 TI - [Eating disorders. Prepubertal anorexia nervosa]. AB - AN UNCOMMON CONDITION: Anorexia nevrosa in the prepubertal period occurs more frequently in boys than common anorexia nevrosa and is characterized by rapid major weight loss more so than by signs of bulimia. ASSOCIATED SIGNS: Depression and volitional disorders are frequently observed together with growth retardation which portends poor prognosis. The patient's personal history (eating disorders during infancy are often found) is an essential factor together with psychiatric conditions in the parents who often have major narcissistic fragility. PMID- 9989306 TI - [Eating disorders. Osteoporosis and infertility after anorexia nervosa]. AB - EATING DISORDERS: The development of somatic complications observed in patients with eating disorders depends both on the duration of the clinical course and on the gravity of the symptoms and psychological factors. It would thus appear advisable to obtain a complete endocrine (gonadotropic, thyroid, hypothalamo hypophyseal-adrenal) work-up which could be repeated every year after the patient has controlled the behavior disorder. Two aspects of these complications predominate: osteoporosis and infertility. OSTEOPOROSIS: A common finding after anorexia nevrosa, osteoporosis can lead to multiple, sometimes spontaneous, fractures. Bone mass can be assessed with biphotonic absorptiometry. The indication for estroprogestogen prophylaxis is debatable, depending on the patient's psychological profile, but also because efficacy has not always been demonstrated. Third-generation biphosphonates appear to offer promising results. INFERTILITY: Among a population of women consulting for infertility, a non negligible percentage have infraclinical manifestations of anorexia nevrosa. The question of prescribing estroprogestogens, which would allow normal cycles and a certain vaginal trophicity, is often raised. We advocate a dose coordination between endocrinologists, infertility specialists and psychiatrists in order to better define the precise modalities of a given treatment aimed at regulating hypothalamo-pituitary function or favoring procreation. PMID- 9989307 TI - [Images in medicine. Melanosis coli]. PMID- 9989308 TI - Anxiety and coronary heart disease: a synthesis of epidemiological, psychological, and experimental evidence. AB - The purpose of this review is to examine the epidemiological, psychological, and experimental evidence for an association between anxiety and coronary heart disease (CHD). Papers published during the years 1980-1996 on anxiety and CHD and relevant publications from earlier years were selected for this review. Epidemiologic evidence suggests that anxiety may be a risk factor for the development of CHD. Chronic anxiety may increase the risk of CHD by: (a) influencing health behaviors (e.g. smoking); (b) promoting atherogenesis (e.g. via increased risk of hypertension); and (c) triggering fatal coronary events, either through arrhythmia, plaque rupture, coronary vasospasm, or thrombosis. Electrophysiologic evidence is particularly compelling: anxiety appears to be associated with abnormal cardiac autonomic control, which may indicate increased risk of fatal ventricular arrhythmias. The strength, consistency, and dose response gradient of the association between anxiety and CHD, together with the biologic plausibility of the experimental evidence, suggest that anxiety may contribute to risk of CHD and that the relationship warrants further investigation. PMID- 9989309 TI - The relation of hostility to lipids and lipoproteins in women: evidence for the role of antagonistic hostility. AB - We examined the relation of antagonistic, neurotic, and cynical hostility to lipids and lipoproteins in 77 healthy women (aged 18-26) selected for having high (> 17) or low (< 12) scores on the Cook-Medley Hostility (Ho) scale. Fasting lipids were determined during the luteal phase of the menstrual cycle for oral contraceptive (OC) non-users (N = 41), and during pills 15-21 for OC users (N = 36). Factor scores for antagonistic and neurotic hostility were derived from a principal component of the Buss-Durkee Hostility Inventory, Spielberger's Anger Expression, and the NEO-Personality Inventory. High Ho scores were significantly associated with higher cholesterol. Antagonistic hostility significantly predicted cholesterol, low density lipoprotein cholesterol, triglycerides, and the ratio of cholesterol to high density lipoprotein cholesterol, with higher antagonistic hostility scores associated with higher levels. Neurotic hostility did not predict lipids. Results suggest a potential pathophysiological mechanism that may contribute to the association between hostility and coronary heart disease. Moreover, a measure of antagonistic hostility, relative to cynical and neurotic hostility, was the best predictor of lipid levels. PMID- 9989310 TI - The effects of marital transitions on changes in physical activity: results from a 10-year community study. AB - The potential effects of making a marital transition on subsequent physical activity were evaluated across a ten-year period in a population-based sample of 302 women and 256 men ages 25 to 75 years. Subjects completed a structured interview at five timepoints throughout the ten-year period during which they reported on their physical activity level as well as marital status. The transition from a married to a single state did not affect physical activity relative to remaining married when analyses of either slopes or mean values were used. In contrast, the transition from a single to a married state resulted in significant positive changes in physical activity relative to remaining single throughout the study period when physical activity slopes, though not means, were compared. The results suggest that marriage may potentially set the stage for natural changes in physical activity that could be capitalized on through appropriate intervention, but additional research is needed to verify this in light of the inconsistent pattern of findings. PMID- 9989311 TI - Contribution of behavior therapy and biofeedback to laxative therapy in the treatment of pediatric encopresis. AB - A model incorporating physiological, behavioral, and psychological parameters are presented to explain the maintenance and consequences of pediatric encopresis. It was hypothesized that the more comprehensive a treatment in addressing these parameters, the more efficacious it would be and the more children it would benefit. Eighty-seven children between the ages of 6 and 15 with the primary complaint of encopresis were randomly assigned to one of three treatments: (a) Intensive Medical Care (IMC), receiving enemas for disimpaction and laxatives to promote frequent bowel movements; (b) Enhanced Toilet Training (ETT), using reinforcement and scheduling to promote response to defecation urges and instruction and modeling to promote appropriate straining, along with laxatives and enemas; or (c) Biofeedback (BF), directed at relaxing the external anal sphincter during attempted defecation, along with toilet training, laxatives, and enemas. Three months following initiation of treatment, ETT and BF produced similar reductions in soiling/child (76% and 65%) that were superior (p's < .04) to IMC (21%). ETT significantly benefited more children than the other two treatments, employing fewer laxatives and fewer treatment sessions at a lower cost. Consistent with the presented model, reduction in soiling was associated with an increase in bowel movements in the toilet, reduction in parental prompting to use the toilet, and defecation pain. These results demonstrate that ETT should be used routinely with laxative therapy in the treatment of chronic encopresis. PMID- 9989312 TI - Postexercise vasodilatation reduces diastolic blood pressure responses to stress. AB - Regular physical exercise is known to reduce cardiovascular risk. We examined the effects of a single bout of moderate bicycle exercise on hemodynamic measures at rest and in response to the foot cold pressor (CP) and mental arithmetic (MA). Sedentary males and females (N = 32) were tested twice, following 20 minutes of moderate exercise (exercise day) versus 20 minutes of quiet rest (control day). Although resting blood pressure was no lower 20 minutes after exercise relative to the same time point on the control day, diastolic blood pressure responses to CP (p = .05) and MA (p = .06) were attenuated on the exercise day. Furthermore, recovery from moderate exercise versus control rest was also associated with reduced vascular resistance index (VRI) at rest and during exposure to both stressors (p's < or = .02). VRI reductions were largest in subjects with elevated vascular tone on the control day and were accompanied by increases in heart rate throughout the postexercise period (p's < or = .004) and higher cardiac index during exercise recovery and in response to CP (p's < or = .05). Thus, the cardiovascular benefit of exercise may in part be due to reduced VRI and attenuated cardiovascular responses to stress during the acute postexercise period. PMID- 9989313 TI - A longitudinal study of work load and variations in psychological well-being, cortisol, smoking, and alcohol consumption. AB - The effects of variations in work load (indexed by paid work hours) on psychological well-being, cortisol, smoking, and alcohol consumption were examined in a sample of 71 workers (44 women, 27 men) in the retail industry. Measures were obtained on four occasions over a six-month period, and assessments were ranked individually according to hours of work over the past seven days. Job strain (demand/control) and job social support were evaluated as potential moderators of responses. Paid work hours ranged from a mean of 32.6 to 48.0 hours per week, and ratings of work-home conflict and perceived stress varied across assessments. Salivary cortisol was inversely associated with job strain and did not vary across sessions. Female but not male smokers consumed more cigarettes during periods of long work hours, and self-reported smoking and cotinine concentrations were greater among smokers with higher nicotine dependency scores. Men but not women with poor social supports consumed more alcohol as work hours lengthened. These data indicate that health behaviors are affected only to a limited extent by variations in work load. Results are discussed in the context of adaptation to work and the pathways linking stressful experience with health risk. PMID- 9989314 TI - Cognitive-behavioral intervention effects on mood and cortisol during exercise training. AB - The purpose of the present study was to assess the effect of a time limited cognitive-behavioral stress management program (CBSM) on mood state and serum cortisol among men and women rowers (N = 34) undergoing a period of heavy exercise training. After controlling for life-event stress (LES), CBSM was hypothesized to reduce negative mood state and cortisol among rowers during a period of heavy training; mood and cortisol changes over the intervention period were hypothesized to be positively correlated. LES was positively associated with negative affect at study entry. After covariance for LES, rowing athletes randomly assigned to the CBSM group experienced significant reductions in depressed mood, fatigue, and cortisol when compared to those randomized to a control group. Decreases in negative affect and fatigue were also significantly associated with cortisol decrease. These results suggest that CBSM may exert a positive effect on athletes' adaptation to heavy exercise training. PMID- 9989315 TI - Correlates of self-efficacy expectation and prediction of walking behavior in cardiac surgery elders. AB - As the number of elderly patients undergoing cardiac surgery (coronary artery bypass and valve replacement) continues to increase, evidence is growing that they can do so with improved health status, functional status, longevity, and life quality. In this article, we used self-efficacy theory to explore one of the most common recovery behaviors--walking various distances. In preoperative data collected in-hospital through data collection at one, two, three, six, and twelve months postoperatively, we explored: (a) the trajectories of self-efficacy expectation (SEE) and self-reported (SR) behavior performance over the first postoperative year; (b) the relationships between SEE and SR behavior; (c) predictors of SEE; and (d) using hierarchical multiple regression, identified predictors of SR behavior at each point of time. The sample (N = 199) was primarily male (76%) with a mean age of 75.8 years. SEE and SR behavior increased over time though with different trajectories; at all points in time, females had lower scores. Correlations between SEE and SR behavior were statistically significant (r values ranging from 0.67 to 0.89; p < .01) for both males and females. Predictors of SEE and SR identified were a mix of physiologic and psychologic constructs. The amount of explained variance in SR behavior scores ranged from a low of 23% at one month to a high of 64.7% at six months. The gender differences sustained one year after cardiac surgery are striking; elder females may need targeted interventions to enhance recovery. PMID- 9989316 TI - Patients' pretreatment expectations of chemotherapy-related nausea are an independent predictor of anticipatory nausea. AB - Based on extensive research with animals, classical conditioning theorists have come to regard contingency as the primary factor in the development of conditioned responses. However, recent experimental work with humans has suggested the possibility that participant expectations may also directly contribute to the development of conditioned responses. To date, this phenomenon has not been investigated in clinical settings. Anticipatory nausea (AN) in chemotherapy patients, widely viewed as the best established example of classical conditioning in clinical medicine, provides an opportunity to examine the contributions of patient expectations to the development of a conditioned response outside the laboratory. The present study of 59 breast cancer patients supported the hypothesis that pretreatment patient expectations make a significant (p < .03) contribution to the development of AN after statistically controlling for the strongest conditioning predictor, contingency. These data imply that patient expectations should be considered when evaluating conditioned responses to aversive medical treatments. PMID- 9989317 TI - It's a function of time: a review of the process approach to behavioral medicine research. AB - In many fields of science, phenomena are studied closely over time to make inferences about patterns of behavior and to allow for predictions of future change and stability. In behavioral medicine, traditional cross-sectional and longitudinal designs are useful for capturing highly stable or slowly-changing phenomena, but important behavior change can be missed by one-occasion measures or infrequent measurements taken at widely-spaced points in time. We review recent research showing how a more complete understanding of many forms of psychological and somatic phenomena can be achieved through intensive measurement within the temporal context in which behavior occurs. This "process approach" to research, conducted in both naturalistic and laboratory settings, is presented here and placed in a methodological and theoretical framework. We also attempt to make recent research on the non-linear dynamics of behavior more accessible by describing and illustrating the uses of time in behavioral medicine research. PMID- 9989318 TI - The comparison of individuals with recurrent tension-type headache and headache free controls in physiological response, appraisal, and coping with stressors: a review of the literature. AB - It is widely accepted that stress plays an important role in the experience of tension-type headache. This article reviews the literature in which individuals with recurrent tension-type headache are compared to headache-free controls in the experience and appraisal of stress, psychophysiological response to stress, and coping with stress. A modified and extended version of the transactional model of stress as it might apply to tension-type headache is used to organize the relevant literature. In summary, there is evidence to suggest that individuals with recurrent tension-type headache experience more stressful events and are more sensitive and have a lower threshold to pain. There are some suggestions that headache sufferers may use different coping strategies for stress and pain. There is little evidence of differences in physiological responses to stressful events. The shortcomings of this body of literature are addressed and directions for future research are identified. PMID- 9989319 TI - Accuracy of smokers' risk perceptions. AB - In response to disagreements about the extent to which smokers recognize the full risk of smoking-induced illness, an attempt was made to review all articles that have investigated smokers' risk perceptions. These diverse studies are grouped here into four categories, depending on the type of risk judgment solicited by researchers. This grouping shows that the apparent underestimation or overestimation of risk depends on how risk perceptions are assessed. No single conclusion about the accuracy of smokers' numerical risk estimates is possible since the accuracy depends entirely on the health outcome rated (e.g. lung cancer versus all deaths due to smoking). With other types of risk questions, smokers consistently acknowledge that smoking increases health risks, but they judge the size of these increases to be smaller and less well-established than do non smokers. Finally, smokers minimize the personal relevance of the risks: they do not believe that they are as much at risk as other smokers of becoming addicted or suffering health effects. The accumulated data indicate that smokers continue to minimize their personal health risks. PMID- 9989320 TI - Perceived importance and satisfaction with physical function in patients with knee osteoarthritis. AB - This investigation examined the determinants of satisfaction with physical function for participants in an Observational Arthritis Study in Seniors (OASIS). The sample consisted of 480 men (51%) and women (49%) over the age of 65 years who had difficulty performing activities of daily living due to knee pain. As part of baseline testing for OASIS, participants completed a measure that assessed satisfaction with function for six physical activities. After controlling for relevant covariates, scores on the satisfaction index were regressed on seven conceptually relevant predictor variables. The results revealed that satisfaction with physical function is a distinct construct from level of function, irrespective of whether the latter variable is measured objectively or subjectively. When entered into a hierarchical regression model, 6 minute walk test data accounted for 11% of the variance in satisfaction scores, whereas perceived difficulty accounted for an additional 22%. Moreover, a significant interaction term between importance and perceived difficulty revealed that patients who rated the activities as important and who had high levels of perceived difficulty had the lowest satisfaction scores. Discussion focuses on the determinants of satisfaction with physical function with emphasis on the interaction between perceived difficulty and importance. PMID- 9989321 TI - Clarification of the conceptualization and measurement of denial in psychosocial oncology research. AB - Denial represents an important area of study in individuals with cancer. It may be related to recognizing symptoms, seeking medical help, psychological adjustment to diagnosis and illness, and perhaps progression of the disease. However, denial has been defined theoretically and measured in a variety of ways. These differences are due to a lack of consensus as to whether denial is unconscious versus conscious, a trait versus a state, an indication of psychological disturbance versus a normal response to a life-threatening disease, or a broad versus a narrow concept. In addition, there is a lack of congruence between theoretical definitions and the operational definitions used in empirical studies investigating denial in the context of cancer. This inconsistency may be responsible for the mixed findings concerning the importance and function of denial in individuals with cancer. In this article, the ways in which denial has been conceptualized and operationalized are examined, and an overview of the research examining denial in cancer patients is provided. We recommend that future studies provide explicit definitions of denial, use multiple measures assessing different modalities and outcomes, measure denial at several times over the course of illness, and take into account aspects of the individual's situation to ensure that denial is not identified erroneously. PMID- 9989322 TI - Implementing preventive services: to what extent can we change provider performance in ambulatory care? A review of the screening, immunization, and counseling literature. AB - Strategies to improve the delivery of preventive care often consist of office based interventions, which are designed to modify provider behaviors or practice patterns. We report on a meta-analysis of 117 behavioral outcomes extracted from 43 studies. Meta-analytic techniques were used to express the results in a common metric, which allowed quantitative comparisons across outcomes. Studies were examined by domains of preventive care (screening, immunization, and counseling) and divided into two groups based on unit of analysis (provider or patient categories). The mean effect size reflects the difference in proportion of physicians providing the targeted behavior between the experimental and comparison groups. In the provider category, the weighted mean effect size for screening was .14, for immunization was .18, and for counseling was .28. In the patient category, the weighted means for screening and immunization were .12 and .15, respectively, but were smaller for the counseling (.08). Because tests for homogeneity of effect sizes were rejected in the patient category, caution in interpreting mean effect sizes is warranted because of variability across individual values. In summary, office-based interventions were found to have positive effects on providers' adherence to preventive recommendations. We discuss the methodological issues and needs for future work to enhance the delivery of preventive services. PMID- 9989323 TI - Measures of hostility as predictors of facial affect during social interaction: evidence for construct validity. AB - We assessed the construct validity of several self-report measures and an interview-based measure of hostility (Interpersonal Hostility Assessment Technique [IHAT]) by evaluating their associations with a behavioral indicator of hostile emotions (facial expressions during social interaction). Participants in the study were 123 volunteers (44% males and 56% females) who were recruited from local community organizations. Self-report measures (Cook-Medley Hostility Scale, Rotter Interpersonal Trust Scale, Buss-Durkee Hostility Inventory, and Spielberger Anger Expression Scale) were represented by factor scores reflecting Overt Hostility, Covert Hostility, and Hostile Beliefs. A canonical correlation analysis identified significant associations between a set of facial affect scores reflecting animosity and various measures of hostility. Specifically, increases in anger and disgust expressions and decreases in happy facial expressions were associated with high IHAT scores and high scores on self-report measures of Hostile Beliefs and Covert Hostility. Women were more expressive than men, especially concerning positive affect, and women had lower scores on self report measures of Hostile Beliefs and Overt Hostility. IHAT scores were uncorrelated with any of the self-report factors which suggests the two assessment techniques are tapping different aspects of the hostility construct. PMID- 9989324 TI - Efficacy of an individualized, motivationally-tailored physical activity intervention. AB - This study compared the efficacy of two low-cost interventions for physical activity adoption. Sedentary (N = 194) adults recruited through newspaper advertisements were randomized to receive either a motivationally-matched, individually-tailored intervention (IT) or a standard self-help intervention (ST). Assessments and interventions were delivered by repeated mailings at baseline, one, three, and six months. Participants were assessed regarding current physical activity behavior, motivational readiness to adopt regular physical activity, and psychological constructs associated with physical activity participation (e.g. self-efficacy, decisional balance). Repeated measures analyses of variance (ANOVAs) revealed significant increases in physical activity participation between baseline and six months for both groups with a significantly greater increase among IT participants. The IT group outperformed the ST group on all primary outcome measures: (a) minutes of physical activity per week, (b) reaching Centers for Disease Control and American College of Sports Medicine (CDC/ACSM) recommended minimum physical activity criteria, and (c) achieving the Action stage of motivational readiness for physical activity adoption. Both groups showed significant improvement between baseline and six months on the psychological constructs associated with physical activity adoption (e.g. self-efficacy), with no significant differences observed between the treatment groups. Utilizing computer expert systems and self-help manuals to provide individually-tailored, motivationally-matched interventions appears to be an effective, low-cost approach for enhancing physical activity participation in the community. PMID- 9989325 TI - Social relationships and the progression of human immunodeficiency virus infection: a review of evidence and possible underlying mechanisms. AB - We review studies examining the quality and quantity of social relationships as potential risk factors for differential progression of human immunodeficiency virus (HIV) infection. Several well-conducted prospective studies suggest that the health effects associated with the presence of supportive social relationships vary according to disease stage and mode of transmission. For gay or bisexual males in the early stages of infection, the presence of supportive social relationships appears to be a risk factor for accelerated disease progression. For individuals in the later stages of infection and those who acquire HIV via intravenous drug use or transfusion, supportive social relationships appear to be associated with health protective effects similar to those observed in other disease settings. We consider a variety of potential explanations for accelerated disease progression in gay men with extensive networks of personal relationships. PMID- 9989326 TI - Recruitment for complementary/alternative medicine trials: who participates after breast cancer. AB - BACKGROUND: Despite the popularity and widespread practice of complementary/alternative medicine (CAM), researchers may face problems accruing patients to randomized clinical trials, considered the gold standard of biomedical research. Strict exclusion criteria and barriers to participation may limit accrual. Inadequate numbers of subjects decrease the ability of studies to detect an effect that exists and generalize their findings. This article describes the recruitment experience of a CAM trial, details reasons for non participation, and contrasts participants and non-participants on demographic, clinical, and treatment-related variables. METHODS: Women who were Houston area residents and spoke English, had primary breast cancer (excluding Stage IV), and were 1 to 30 months posttreatment with no steroids, tamoxifen, substance abuse, psychiatric or heart disease, or immune deficiency were eligible. The enrollment process involved three contacts (i.e. introductory letter and brochure, telephone calls, and reminder post cards). Potential participants were told that the study would require blood samples (30 cc) to assess immune function; psychosocial measures to assess emotional well-being, quality-of-life, social support, and coping strategies; and possible assignment to six weekly support or imagery sessions. Factors influencing recruitment and reasons for non-participation were assessed by stratified analysis and multivariate logistic regression. RESULTS: Of 158 eligible participants, 30% (N = 47) consented to participate. Primary reasons for non-participation included work/childcare (33.3%), transportation/travel (30.6%), and lack of interest (24.3%). Participants were more likely to be 40-54 years of age versus younger or older, divorced/separated, and able to pay some/all medical expenses. Divorced or separated women appeared to be more likely to participate, regardless of financial status. CONCLUSIONS: Researchers must assess the impact of exclusion criteria on accrual and recognize the special needs of their target population. Although age, marital status, and pay status were the strongest predictors of participation, these factors are not amenable to intervention. Based on this study, researchers might boost accrual by providing interventions available during the day and evening to accommodate working women, child care services, transportation, or reimbursement for travel costs. PMID- 9989327 TI - Psychosocial stress moderates the relationship of cancer history with natural killer cell activity. AB - Data suggest that both cancer history and psychosocial stress may be associated with reductions in natural killer cell activity (NKA). Therefore, we tested whether individual differences in cancer history, chronic/perceived stress, and their interactions would be associated with decreased levels of NKA. We tested these hypotheses in 80 spouse caregivers of victims of Alzheimer's Disease (AD) (persons known to report high levels of psychosocial stress) and in 85 age- and sex-matched spouses of non-demented controls. Participants were assessed at study entry (Time 1) and 15-18 months later (Time 2). Individuals with cancer histories (N = 43) had not been treated with immune altering medications within the last year. At both Times 1 and 2, cross-sectional main effects were weak or absent for cancer history, perceived stress (e.g. high hassles, low uplifts), and caregiver status; however, interactions occurred between cancer history and perceived stress, such that persons with cancer histories and high hassles/low uplifts had the lowest NKA values (p < .05). These results occurred even after controlling for age, gender, beta-blocker use, hormone replacement therapy, alcohol, and exercise. At Time 1, an interaction also occurred between caregiver status and cancer history--caregivers with cancer histories had lower NKA than did controls with cancer histories and caregivers/controls without cancer histories (p < .05). At Time 2, this interaction only showed a trend (p < .08), primarily because caregivers with cancer histories experienced increases in NKA (p < .05) from Time 1 to Time 2, whereas in the other three groups NKA did not change. Importantly, in caregivers with cancer histories, high perceived stress at Time 1 predicted low NKA at Time 2 (p < .05). This research suggests that the combinations of biological vulnerabilities and chronic/perceived stress may have interactive effects resulting in reduced NKA. PMID- 9989328 TI - Personality and coronary heart disease: the type-D scale-16 (DS16). AB - Clinical diagnoses of depression, self-reported negative emotions, and personality traits have been associated with both the development and progression of coronary heart disease (CHD). This article focusses on negative affectivity (the tendency to experience negative emotions) and social inhibition (the tendency to inhibit self-expression in social interaction) in CHD patients. Two independent samples of patients with CHD were included in this study. Both empirical and internal-structural criteria were used to devise a brief self report measure comprising an eight-item negative affectivity and an eight-item social inhibition scale in Sample 1 (N = 400). These scales were internally consistent (alpha = .89 and .82), stable over time (three-month test-retest reliability = .78 and .87) and were validated against standard personality scales. CHD patients with a "distressed" personality (Type-D) report high levels of negative affectivity and social inhibition; accordingly, this self-report measure was termed Type-D Scale-16 (DS16). Previous research showed that Type-D was associated with cardiac events and incidence of cancer in patients with CHD. Type-D as measured by the DS16 was associated with depressive affect and symptoms, stress, poor self-esteem, dissatisfaction with life, and low positive affect in Sample 2 (N = 100) of the present article. It is concluded that research on CHD should focus on affective disorder, specific negative emotions, and global personality traits, and that the DS16 is a practical, sound research tool that can be used to assess Type-D. PMID- 9989329 TI - Reaching those most in need: participation in a Planned Parenthood smoking cessation program. AB - We evaluated the representativeness of women approached and enrolled in a brief smoking cessation intervention conducted in Planned Parenthood clinics. In this effectiveness study, regular clinic staff were trained to identify, offer participation, and counsel willing smoking clients as part of their clinic visit. Chart audits were conducted to determine the percent of clients who had smoking status identified, as well as the percent and characteristics of potentially eligible clients who were not approached. Baseline and non-participant questionnaires were analyzed to determine participation rate and characteristics of those participating versus those not participating. Smoking status was documented in 99% of charts. Seventy percent of eligible smokers were approached about study participation and 74% of those approached participated. There were no significant differences between those approached and those not approached or between those who participated versus those who did not on a host of sociodemographic variables. This project was able to approach and attract a representative sample of young, lower income women to participate in a brief, clinic-based smoking cessation program. PMID- 9989330 TI - Psychosocial variables, age, and angiographically-determined coronary artery disease in women. AB - The present study explored the relationship between psychosocial measures and the degree of coronary stenosis in a sample of 59 women between the ages of 39 and 84. Coronary occlusion was correlated with elevated cholesterol and marginally correlated with age and was inversely associated with years of education. Based on hierarchical multiple regression, an interview-based measure of hostility was associated with coronary stenosis after controlling for traditional risk factors, and age moderated the hostility-stenosis relationship. Further, a second regression model suggested that trait anxiety was inversely correlated with degree of occlusion, perhaps because low-anxious women are referred for catheterization later in the course of the disease. Contrary to hypotheses, there was no evidence that repression of interview-based hostility or anxiety predicted coronary occlusion. Given the small sample size, results should be considered preliminary. Future studies should explore the degree to which anxiety and hostility are associated with coronary heart disease (CHD) in larger samples of women and the degree to which age moderates the hostility-occlusion association. PMID- 9989331 TI - Prevalence of binge eating disorder, obesity, and depression in a biracial cohort of young adults. AB - This article examined the prevalence of binge eating disorder (BED), obesity, and depressive symptomatology in a biracial, population-based cohort of men and women participating in a longitudinal study of cardiovascular risk factor development. The Revised Questionnaire on Eating and Weight Patterns was used to establish BED status among the 3,948 (55% women, 48% Black) participants (age 28-40 years). Body mass index (BMI: kg/m2) was used to define overweight (BMI > or = 27.3 in women and > or = 27.8 in men). Depressive symptomatology was assessed with the Center for Epidemiologic Study Depression Scale. Prevalence of BED was 1.5% in the cohort overall, with similar rates among Black women, White women, and White men. Black men had substantially lower BED rates. Depressive symptomatology was markedly higher among individuals with BED. Among overweight participants, BED prevalence (2.9%) was almost double that of the overall cohort. There were no differences in BED rates between over-weight Black and White women. Thus, BED was common in the general population, with comparable rates among Black women, White women, and White men, but low rates among Black men. Obesity was associated with substantially higher prevalence of BED. Treatment studies that target obese men and minority women with BED are indicated. PMID- 9989332 TI - Psychosocial factors in nutrition education for hypercholesterolemic children. AB - The goals were to assess psychosocial effects of labeling children as hypercholesterolemic and to measure changes in child well-being as a function of participation in nutrition education interventions. Older (6-10 years old) and younger (4-6 years old) children with (> 4.55 mmol/l; > 176 mg/dL) and without elevated total cholesterol levels were identified by cholesterol screening. Psychosocial functioning (self-esteem, perceived dietary competence, health beliefs, parental control of eating) was assessed and at-risk children were randomized into a home-based, self-contained nutrition education program (the Parent-Child Autotutorial, or PCAT program), dietary counseling with a registered dietician, or an at-risk control group. At three, six, and twelve months following baseline, children's psychosocial functioning again was assessed; parents also provided data at baseline, three months, and twelve months. Analyses of data from 189 at-risk and 74 not-at-risk children revealed that: (a) Older hypercholesterolemic children reported poorer health beliefs than non-labeled children; (b) Older girls in nutrition education programs reported lower self esteem than control group girls; (c) Older children's feelings of efficacy at choosing a healthful diet were positively related to their health beliefs and self-esteem; (d) Younger children's reports of parents' dietary control were negatively related to children's feelings of acceptance; and (e) Parents of older children in the PCAT program reported increases over time in children's ability to choose a healthful diet. The quasi-experimental design means that conclusions about negative labeling effects should be drawn cautiously, but the evidence suggests that education interventions can have an impact on child efficacy and potentially child adjustment. Factors associated with adverse reactions to labeling (parental control or feelings of efficacy) should be taken into account in the development of intervention programs for children. PMID- 9989333 TI - [Ronald Ross: a century of the transfer of malaria by mosquitoes]. AB - Ronald Ross is a brilliant and polyvalent mind. When orientated towards medicine he took the training amateurishly and ended up with a limited qualification. After 2 years as a ship doctor, he attended the compulsory complementary training in order to be admissible in the IMS, the garrison life left him with plenty of time to engage in his hobby's: painting for a short while, writing, poetry and mathematics. By the end of his first term he questioned the sense of his medical activities and decided, with a view to his career, to acquire a Public Health diploma and some complementary bacteriology. During his second term the malaria problem drew his attention. As he was unable to detect the parasite of Laveran in the blood of patients with malarial fevers he concluded that the parasite had been some lucky microscopic finding without any value and turned this parasite into ridicule. During his leave in 1894 he met Manson, who showed him the technique to put the parasite in evidence and convinced him to search for its vector which, to his opinion, should be a mosquito. Ross decided to follow this lead. With his minimal parasitological knowledge and an entomological background limited to the external appearance of mosquitoes he endeavoured to establish the life cycle of the malarial parasites. Notwithstanding some service bounded transfers, he followed the fate of the filaments of the crescents and discovered the parasite on the stomachwall of dapled-winged mosquitoes. During his special mission in Calcutta and in the absence of suitable malaria infections in man he shifted to bird proteosoma (now P. relictum) with a grey mosquito (culex) as vector. He demonstrated the complete life-cycle ending in the salivary glands of the mosquitoes and succeeded in transmitting this infection by mosquito-bites in healthy birds. This climax in his research was crowned by the attribution in 1902 of the Nobel Prize for Medicine. In the mean time he resigned from the IMS and was appointed as "Lecturer on Tropical Diseases" at the Liverpool School. He reoriented his activities to the prevention of malaria by control of the vector in its aquatic larval stage, which he tried out and promoted during his journeys to the West African Coast and other countries. His current were variegated but without salient details. Through the survey of the parasite index and the assessment of the spleen rate in children he founded the malariometry as a epidemiological tool, focussed attention on the relation of malaria and the community and on the complexity of the transmission dynamics. By handing in his resignation at the Liverpool School and moving to London he hampered further his scientific productivity. The tardy foundation of the Ross Institute did not stimulate a new impetus. He suffered a stroke which left him partially crippled an he died in his Institute. PMID- 9989334 TI - Regulation of alternative processing of the sarco/endoplasmic reticulum Ca2+ ATPase (SERCA2) gene transcripts during muscle differentiation. AB - The Ca2+ transport ATPases of the sarcoplasmic or endoplasmic reticulum (SERCA) mediate the uptake of Ca2+ into intracellular stores. These Ca2+ pumps are encoded by three different genes. Alternative processing of the SERCA2 messenger generates two different protein isoforms. These two isoforms differ in their C terminal part and this divergence is responsible for the functional difference between SERCA2a and SERCA2b. The aim of this study was to characterise the cis active elements and the trans-acting factors required for the generation of the muscle-specific messenger during myogenic differentiation. A competition model between muscle-type splicing and non-muscle polyadenylation was excluded as inactivation of the non-muscle polyadenylation site did not induce muscle-type splicing in non-muscle or in undifferentiated muscle cells. We therefore propose that the expression of the SERCA2a isoform is due to the regulation of the muscle specific splice process during myogenic differentiation. We characterised the spatial and sequence requirements essential for tissue-specific transcript processing. It was demonstrated that the processing signals in the transcript, i.e. both donor splice sites and the polyadenylation site located in the muscle specific intron, have to be weak. An exception to this rule is the 3' acceptor splice site that has to be strong in order to get muscle-specific splicing. We also found an inverse relationship between intron length and splice efficiency as shortening the terminal intron resulted in muscle-specific splicing in non-muscle and in undifferentiated muscle cells. Finally, it was demonstrated that sequences around the muscle-specific acceptor region as well as in the muscle-specific exon are required to prevent muscle-specific splicing in undifferentiated muscle cells. Especially a region upstream of the 3' acceptor contains important sequence information required for the inhibition of muscle-specific splicing. It was demonstrated that the trans-acting factors regulating the alternative SERCA2 splicing are muscle specific. First, myogenin, a transcription factor that plays a key role in muscle differentiation, induced muscle-specific SERCA2 splicing in a fibroblast cell line. Second, changes in general splice and polyadenylation efficiency, as observed during B-cell maturation, did not affect SERCA2 splicing. Finally, expression and overexpression studies did not support the hypothesis that changes in the level of the alternative splice factor ASF or other arginine and serine rich proteins are involved in the regulation of muscle-specific splicing. We conclude that muscle-specific SERCA2a expression is a tightly regulated process dependent on the inhibition of the muscle-specific splice process at the 3' end of the primary transcript. During differentiation this inhibition is overcome by the downregulation of an inhibitory factor and/or the expression of a positive trans-acting factor. PMID- 9989335 TI - Heritable collagen disorders: from phenotype to genotype. AB - Genetic disorders of collagen comprise a heterogeneous group of disease with pleiotropic manifestations and monogenic inheritance. They are caused by mutations in genes encoding collagen proteins or enzymes involved in collagen biosynthesis. New insights into the molecular basis of two of these conditions are presented here. In Osteogenesis Imperfecta (OI) characterized by bone fragility, mutations in the COL1A1 or the COL1A2 genes encoding type I collagen are associated with a wide spectrum of phenotypes, varying from mild to severe and lethal conditions. The mild forms are usually caused by haploinsufficiency mutations in the COL1A1 gene while the severe and lethal forms result from dominant negative mutations in COL1A1 or COL1A2. Several collagen types are involved in the Ehlers-Danlos syndromes (EDS), of which skin hyperelasticity, joint hypermobility and vascular fragility are the principal features. Six different genetic subtypes are recognised. Structural mutations in collagen type I, III or V underly the dominant forms, whereas recessive EDS subtypes are associated with enzymatic defects of collagen type I biosynthesis. Clinical application of biochemical and molecular collagen analysis has greatly improved quality of diagnosis, genetic counselling and management of these heritable disorders. PMID- 9989336 TI - Indinavir-fluconazole interaction. PMID- 9989337 TI - Molecular characterization of a ceftazidime-resistant Morganella morganii isolate producing a TEM-10 beta-lactamase. PMID- 9989338 TI - Cefepime versus ceftriaxone for empiric treatment of hospitalized patients with community-acquired pneumonia. PMID- 9989339 TI - The pharmacokinetic principles behind scaling from preclinical results to phase I protocols. AB - Extrapolation of animal data to assess pharmacokinetic parameters in humans is an important tool in drug development. Allometric scaling has many proponents, and many different approaches and techniques have been proposed to optimise the prediction of pharmacokinetic parameters from animals to humans. The allometric approach is based on the power function Y = aWb, where the bodyweight of the species is plotted against the pharmacokinetic parameter of interest on a log-log scale. Clearance, volume of distribution and elimination half-life are the 3 most frequently extrapolated pharmacokinetic parameters. Clearance is not predicted very well (error between predicted and observed clearance > 30%) using the basic allometric equation in most cases. Thus, several other approaches have been proposed. An early approach was the concept of neoteny, where the clearance is predicted on the basis of species bodyweight and maximum life-span potential. A second approach uses a 2-term power equation based on brain and body weight to predict the intrinsic clearance of drugs that are primarily eliminated by phase I oxidative metabolism. Most recently, the use of the product of brain weight and clearance has been proposed. A literature review reveals different degrees of success of improved prediction with the different methods for various drugs. In a comparative study, the determining factor in selecting a method for prediction of clearance was found to be the value of the exponent. Integration of in vitro data into in vivo clearance to improve the predictive performance of clearance has also been suggested. Although there are proponents of using body surface area instead of bodyweight, no advantage has been noted in this approach. It has also been noted that the unbound clearance of a drug cannot be predicted any better than the total body clearance (CL). In general, there is a good correlation between bodyweight and volume of the central compartment (Vc); hence, Vc does not face the same complications as CL. The relationship between elimination half-life (t 1/2 beta) and bodyweight across species results in poor correlation, most probably because of the hybrid nature of this parameter. When a reasonable prediction of CL and Vc is made, t 1/2 beta may be predicted from the equation t 1/2 beta = 0.693 Vc/CL. PMID- 9989341 TI - Clinical pharmacokinetics of cisatracurium besilate. AB - Cisatracurium besilate, one of the 10 stereoisomers that comprise atracurium besilate, is a nondepolarising neuromuscular blocking agent with an intermediate duration of action. Following a 5- to 10-sec intravenous bolus dose of cisatracurium besilate to healthy young adult surgical patients, elderly patients and patients with renal or hepatic failure, the concentration versus time profile of cisatracurium besilate is best characterised by a 2-compartment model. The volume of distribution (Vd) of cisatracurium besilate is small because of its relatively large molecular weight and high polarity. Cisatracurium besilate undergoes Hofmann elimination, a process dependent on pH and temperature. Unlike atracurium besilate, cisatracurium besilate does not appear to be degraded directly by ester hydrolysis. Hofmann elimination, an organ independent elimination pathway, occurs in plasma and tissue, and is responsible for approximately 77% of the overall elimination of cisatracurium besilate. The total body clearance (CL), steady-state Vd and elimination half-life of cisatracurium besilate in patients with normal organ function are approximately 0.28 L/h/kg (4.7 ml/min/kg), 0.145 L/kg and 25 minutes, respectively. The magnitude of interpatient variability in the CL of cisatracurium besilate is low (16%), a finding consistent with the strict physiological control of the factors that effect the Hofmann elimination of cisatracurium besilate (i.e. temperature and pH). There is a unique relationship between plasma clearance and Vd because the primary elimination pathway for cisatracurium besilate is not dependent on organ function. There are minor differences in the pharmacokinetics of cisatracurium besilate in various patient populations. These differences are not associated with clinically significant differences in the recovery profile of cisatracurium besilate, but may be associated with differences in the time to onset of neuromuscular block. PMID- 9989340 TI - Clinical pharmacokinetics of sevoflurane. AB - Sevoflurane is a comparatively recent addition to the range of inhalational anaesthetics which has been recently released for clinical use. In comparison to older inhalational agents such as isoflurane or halothane, the most important property of sevoflurane is its low solubility in the blood. This results in a more rapid uptake and induction than the 'older' inhalational agents, improved control of depth of anaesthesia and faster elimination and recovery. The more rapid pharmacokinetics are a result of the low blood/gas partition coefficient of 0.69. With an oil/gas partition coefficient of 47.2, the minimum alveolar concentration (MAC) of sevoflurane is 2.05%. Two to 5% of the drug taken up is metabolised by the liver. The pharmacokinetics of sevoflurane do not change in children, obese patients or patients with renal insufficiency. The pharmacokinetics and pleasant odour of sevoflurane make mask induction feasible, which is an obvious advantage in paediatric anaesthesia. The hepatic metabolism of sevoflurane results in the formation of inorganic fluoride. Upon contact with alkaline CO2 absorbent, a small amount of sevoflurane is degraded and a metabolite (compound A) is formed and inhaled in trace amounts. Whether inorganic fluoride or compound A are nephrotoxic is presently a matter of controversy. PMID- 9989343 TI - Recent advances in the pharmacokinetics of local anaesthetics. Long-acting amide enantiomers and continuous infusions. AB - The most widely used long-acting amide local anaesthetic is bupivacaine, a racemic mixture of 2 stereoisomers. However, there is evidence that the use of single enantiomer compounds offers advantages over racemic agents. Ropivacaine, the recently introduced propyl homologue of bupivacaine, is a pure S-(-) enantiomer. It is associated with a reduced incidence of both cardiovascular and central nervous system toxicity, a concern with racemic bupivacaine, in preclinical studies. The relevant pharmacokinetic differences include a lower lipid solubility, a slightly higher plasma clearance and shorter elimination half life (t 1/2 beta) compared with racemic bupivacaine, with a similar degree of plasma protein binding. More recently levobupivacaine, the pure S-(-)-enantiomer of bupivacaine, has been produced. Stereoselective differences have been observed between the 2 enantiomers and the racemic mixture, with levobupivacaine exhibiting a slightly higher degree of plasma protein binding, a lower volume of distribution, a higher plasma clearance, and a shorter t 1/2 beta than the R-(+) enantiomer. In common with ropivacaine, levobupivacaine has been shown to have a reduced incidence of toxicity in comparison the R-(+)-enantiomer in preclinical studies, explained in part by a reduced affinity to both brain and myocardial tissue. Racemic bupivacaine is increasingly administered by continuous infusion to provide prolonged postoperative analgesia. The pharmacokinetic profile of the drug administered in this manner has only recently been elucidated and indicates a slow rise in total plasma concentration with increasing duration of infusion, mitigated by changes in plasma protein concentrations during the postoperative period. This appears to be the predominant reason why complications related to systemic toxicity are rarely observed with this technique. However, continuous administration of individual enantiomers may potentially serve as a safer option in the future. PMID- 9989344 TI - Potential role of the anterior cingulate cortex in PTSD: review and hypothesis. AB - Many symptoms of PTSD represent conditioned responses to stimuli associated with a traumatic experiences. In this review, we propose that the anterior cingulate- a brain region that appears to be involved in fear-conditioning--is dysfunctional in PTSD, thus facilitating exaggerated emotional and behavioral responses (hyperarousal) to conditioned stimuli. Preclinical studies suggest that the anterior cingulate may serve a critical gating function in modulating conditioned fear responses. As such, this region would be a key component of a neural circuit involved in the pathophysiology of PTSD. An amygdala-locus coeruleus-anterior cingulate circuit may be consistent with evidence for chronic noradrenergic activation documented in PTSD patients. According to this model, efferent noradrenergic projections from the locus coeruleus may dampen anterior cingulate function. This in turn would allow myriad external or internally driven stimuli to produce the exaggerated emotional and behavioral responses characteristic of PTSD. If confirmed in future research, cingulate dysfunction would have important theoretical and treatment implications. PMID- 9989342 TI - Clinical pharmacokinetics of lamivudine. AB - Lamivudine (3TC), the negative enantiomer of 2'-deoxy-3'-thiacytidine, is a dideoxynucleoside analogue used in combination with other agents in the treatment of human immunodeficiency virus type 1 (HIV-1) infection and as monotherapy in the treatment of hepatitis B virus (HBV) infection. Lamivudine undergoes anabolic phosphorylation by intracellular kinases to form lamivudine 5'-triphosphate, the active anabolite which prevents HIV-1 and HBV replication by competitively inhibiting viral reverse transcriptase and terminating proviral DNA chain extension. The pharmacokinetics of lamivudine are similar in patients with HIV-1 or HBV infection, and healthy volunteers. The drug is rapidly absorbed after oral administration, with maximum serum concentrations usually attained 0.5 to 1.5 hours after the dose. The absolute bioavailability is approximately 82 and 68% in adults and children, respectively. Lamivudine systemic exposure, as measured by the area under the serum drug concentration-time curve (AUC), is not altered when it is administered with food. Lamivudine is widely distributed into total body fluid, the mean apparent volume of distribution (Vd) being approximately 1.3 L/kg following intravenous administration. In pregnant women, lamivudine concentrations in maternal serum, amniotic fluid, umbilical cord and neonatal serum are comparable, indicating that the drug diffuses freely across the placenta. In postpartum women lamivudine is secreted into breast milk. The concentration of lamivudine in cerebrospinal fluid (CSF) is low to modest, being 4 to 8% of serum concentrations in adults and 9 to 17% of serum concentrations in children measured at 2 to 4 hours after the dose. In patients with normal renal function, about 5% of the parent compound is metabolised to the trans-sulphoxide metabolite, which is pharmacologically inactive. In patients with renal impairment, the amount of trans-sulphoxide metabolite recovered in the urine increases, presumably as a function of the decreased lamivudine elimination. As approximately 70% of an oral dose is eliminated renally as unchanged drug, the dose needs to be reduced in patients with renal insufficiency. Hepatic impairment does not affect the pharmacokinetics of lamivudine. Systemic clearance following single intravenous doses averages 20 to 25 L/h (approximately 0.3 L/h/kg). The dominant elimination half-life of lamivudine is approximately 5 to 7 hours, and the in vitro intracellular half-life of its active 5'-triphosphate anabolite is 10.5 to 15.5 hours and 17 to 19 hours in HIV-1 and HBV cell lines, respectively. Drug interaction studies have shown that trimethoprim increases the AUC and decreases the renal clearance of lamivudine, although lamivudine does not affect the disposition of trimethoprim. Other studies have demonstrated no significant interaction between lamivudine and zidovudine or between lamivudine and interferon-alpha-2b. There is limited potential for drug-drug interactions with compounds that are metabolised and/or highly protein bound. PMID- 9989345 TI - Subtypes of social phobia in adolescents. AB - Thirty-three social phobic adolescents were asked to name their ten most feared social situations. Two independent judges classified each situation reported by the participants into one of four situational domains: formal speaking/interactions, informal speaking/interactions, observation by others, and assertion. Fifteen participants (45.5%) were assigned a generalized subtype of social phobia because they endorsed at least moderate anxiety in all four situational domains. This subgroup scored higher on self-report measures of anxiety and depression than the rest of the sample. These results provide empirical support for the existence of subtypes of social phobia in adolescents. PMID- 9989346 TI - Frequency of panic attacks and panic disorder in adolescents. AB - By using data from the Bremer Adolescent Study, this report presents findings on the frequency, comorbidity, and psychosocial impairment of panic disorder and panic attacks among 1,035 adolescents. The adolescents were randomly selected from 36 schools in the province of Bremen, Germany. Panic disorder and other psychiatric disorders were coded based on DSM-IV criteria using the computerized assisted personal interview of the Munich version of the Composite International Diagnostic Interview. Panic disorder occurred rather rare, with only 0.5% of all the adolescents met the DSM-IV criteria for this disorder sometimes in their live. Panic attack occurred more frequently, with 18% of the adolescents reported having had at least one panic attack. Slightly more girls than boys had panic attack and panic disorder. The occurrence of panic attack and panic disorder were the greatest among the 14-15 year olds. The experience of having a panic attack was associated with a number of problems, the most frequent being avoiding the situation for fear of having another attack. Four most common symptoms associated with a panic attack were that of palpitations, trembling/shaking, nausea or abdominal distress, and chills or hot flushes. Panic disorder comorbid highly with other psychiatric disorder covered in our study, especially with that of major depression. Among those with a panic disorder, about 40% of them were severely impaired during the worst episode of their illness. Only one out of five adolescents with panic disorder sought professional help for emotional and psychiatric problems. The implication of our findings for research and clinical practice are discussed. PMID- 9989347 TI - Psychological responses in family members after the Hebron massacre. AB - The authors attempted to determine the frequency of severe psychological responses in surviving family members in a religious Muslim culture. Twenty-three wives, twelve daughters and twenty-six sons of heads of households massacred while praying in the Hebron mosque on 25 February 1994 were interviewed with the clinician-administered PTSD scale; 50% of daughters, 39% of wives, and 23% of sons met criteria for PTSD. PTSD or traumatic bereavement occurs with high frequency after a major tragedy in a Moslem society, despite religious admiration of dead martyrs. PMID- 9989348 TI - Progress in psychosocial assessment and treatment. AB - In this second review on research examining psychosocial cognitive-behavioral, and basic behavioral research, we focus on recent findings pertaining to: (a) relevant psychological constructs in anxiety, and (b) the treatment of anxiety. We first present several studies in which researchers investigated psychological models or constructs with the aim of enhancing the current understanding of the development and persistence of anxiety. Most of these studies also have implications for the treatment of anxiety disorders. We go on to review studies exploring novel approaches to the treatment of persons with anxiety. PMID- 9989349 TI - Computer-assisted rating scales for social phobia: reliability and validity may not be what they appear. PMID- 9989350 TI - [Neurosonology in cerebrovascular diseases]. PMID- 9989351 TI - [Molecular genetic studies of epilepsies]. PMID- 9989352 TI - [Clinical features and treatment of sarcoidosis involving the central nervous system]. AB - PURPOSE: The purpose of this study was to investigate the clinical features, diagnosis, and treatment modalities of three cases with neurosarcoidosis, which involved the central nervous system (CNS). CASES: Three men with neurosarcoidosis, aged 27, 29 and 60 years, are presented. Two of them had previously been given a diagnosis of sarcoidosis. The clinical symptoms of these cases included diabetes insipidus, pituitary dysfunction, seizure, mental disorder, visual field disturbance and pyramidal tract signs. In these cases, CT scan and MRI showed the presence of a tumor near the pituitary gland, diffuse nodules in the subarachnoid space or meningoencephalitis associated with angitis. The level of angiotensin converting enzyme (ACE) in the sera and in the cerebrospinal fluid, were elevated in the two cases who had no brain biopsy. All three cases were treated with steroids; two of them received pulse steroid therapy. RESULTS: The two cases who received pulse steroid therapy responded quickly, with improvement in clinical features, serum ACE levels and neuroradiological findings. Under oral administration of steroids, all three cases recovered with complete remission of neurosarcoidosis except for endocrinological symptoms. DISCUSSION: The main pathological changes of neurosarcoidosis are granulomatous angitis of the venular walls and occasionally, of the capillaries near the meninx and Virchow-Robin space. The patients also had symptoms of secondary meningoencephalitis. These changes were mainly located in the hypothalamus and pituitary gland. The patients had complex symptoms resulting from endocrine system granuloma, as well as from cerebral ischemia. The severity of the disease and effectiveness of treatment, can be evaluated by measuring ACE levels in the cerebrospinal fluid (over 1. 0 IU/l), and by Gd-enhanced MRI. Early pulse steroid therapy with subsequent oral steroid administration is thought to be important for neurosarcoidosis treatment, in order to prevent irreversible damage in the CNS. PMID- 9989353 TI - [Comparison of clinical pictures of mitochondrial encephalomyopathy with tRNA(Leu(UUR)) mutation in 3243 with that in 3254]. AB - We compared clinical pictures of a case of mitochondrial encephalomyopathy with tRNA(Leu(UUR)) point mutation at nucleotide position 3254 of mitochondrial DNA with those at position 3243. The mutation 3254 was a 19-year-old male patient with cardiomyopathy accompanied with muscle atrophy. The first mutant 3243 was a 31-year-old female patient showing clinical features of MELAS and endocrinological abnormalities. The second 3243 mutant was a 27-year-old male patient who had an external ophthalmoplegia and slight mental decline. In all cases, muscle biopsy specimen showed ragged red fibers and strongly SDH-reactive blood vessels, but their limb weakness were unremarkable. These results suggest that tRNA(Leu(UUR)) point mutation 3254 exhibits similar clinical phenotypes as those observed in 3243 mutant. PMID- 9989354 TI - [Effects of selegiline hydrochloride on intracellular Ca2+ contents in cultured neuronal cells]. AB - The effects of Selegiline hydrochloride (Selegiline HCl) on the intracellular Ca2+ contents of primarily cultured rat striatal, mesencephalic neuronal cells and PC-12 cells were examined by the use of a Ca2+ imaging analyzer. In the former two cell types, Selegiline HCl (10(-5)-10(-6) M) induced a transient inflow of extracellular Ca2+ through the voltage-dependent N-type Ca2+ channel. In addition, all cells indicating an increase in the intracellular Ca2+ content were found to be catecholaminergic neurons which showed a positive reaction with anti-tyrosine hydroxylase antibodies. Furthermore, a transient intracellular influx of Ca2+ was observed in the NGF-pretreated PC-12 cells. From these results, it is suggested that Selegiline HCl elicits various functions, including antioxidation, activation of neurotrophic factor biosynthesis and neuronal protection probably via an unidentified specific proteins of tyrosine hydroxylase positive neurons. PMID- 9989355 TI - [Inhibition of fibroblast growth factor receptor 1 expression in human glioblastoma cell contributes to the cell growth suppression]. AB - Although normal human astrocytes rarely express fibroblast growth factor receptor 1 (FGFR 1) mRNA, expression of FGFR 1 mRNA in astrocytomas increases as malignancy progresses. This result suggests that FGFR 1 can be one of important factors for glioblastoma cell growth. In our study, specific antisense oligonucleotides for FGFR 1 mRNA inhibited cell growth of SNB 19, human glioblastoma cell line, while sense oligonucleotides showed no cell reduction. And Southern blot analysis demonstrated decreased expression of FGFR 1 mRNA in only antisense group. Furthermore, cross-linking analysis revealed decreased number of FGFR 1 in antisense-treated SNB 19 in protein level. These results conclude that cell growth inhibition was caused by suppression of both transcription and translation of FGFR 1 mRNA. Interestingly, alpha-specific antisense also inhibited expression of beta-, and gamma-type of FGFR 1 mRNA which had no binding sites for the oligonucleotides. This fact indicates that antisense oligonucleotides binds to premature mRNA, which is previous form of mature mRNA before splicing, in nucleus. It is previously reported that basic fibroblast growth factor (bFGF), major ligand to FGFR 1, was overly expressed in human malignant astrocytomas. Thus, increased number of FGFR 1 may contribute to the acceleration of bFGF autocrine or paracrine mechanism in glioblastoma. PMID- 9989356 TI - [A case of polyneuropathy by microscopic polyarteritis nodosa]. AB - We report a 59-year-old man with chronic sensorimotor polyneuropathy mimicking chronic inflammatory demyelinating polyneuropathy. Sural nerve biopsy revealed marked loss of myelinated fibers and myelin ovoid formation with vasculitis in the epineurium. Renal biopsy was performed subsequently because of the laboratory findings suspecting systemic vasculitis of which consisted CRP positivity, ESR elevation, perinuclear antineutrophil cytoplasmic antibodies (pANCA), and creatinine clearance reduction. The biopsy specimen revealed segmental necrotizing glomerulonephritis with frequent formation of a crescent. These findings confirmed the diagnosis of microscopic polyangitis. Oral administration of prednisolone with additional azathioprine following ethylprednisolone pulse therapy was effective, and pANCA was not detected anymore. We conclude that vasculitic neuropathy has to be considered as a possible cause of polyneuropathy. PMID- 9989357 TI - [Intracranial hemorrhage observed in the cases of cervical internal carotid artery occlusion associated with moyamoya disease-like vessels]. AB - We report on two peculiar cases of intracranial hemorrhage due to the rupture of moyamoya disease-like vessels associated with unilateral internal carotid occlusion at its origin. The first case is 44-year-old male showing intraventricular hemorrhage associated with right internal carotid occlusion. The second case is 58-year-old female presenting sub-arachnoid hemorrhage associated with left internal carotid occlusion. Although both cases showed the unique appearance of collateral flow resembling moyamoya disease, they were not classified as moyamoya disease nor unilateral Moyamoya-like state. Vascular abnormality such as cerebral aneurysm and arteriovenous malformation were not at all detected. The etiology of hemorrhage for both cases is presumed as the rupture of moyamoya disease-like vessels, however, it is unable for us to determine why the one case showed IVH, yet the other showed SAH. The two cases showed hypoperfusion of ipsilateral cerebral hemisphere on SPECT that followed by the external-internal carotid revascularization surgery in the chronic stage. Post operative study proved the improvement of the CBF reserve. Nevertheless, whether the reconstructive vascularization prevent an occurrence of rebleeding needs the longer observation and the accumulation of the resembling cases. PMID- 9989358 TI - [Cerebral infarction associated with nephrotic syndrome in a young adult: a case report]. AB - We report a 19-year-old man who developed a cerebral infarction in the territory of the anterior choroidal artery and showed a hypercoagulable state and nephrotic syndrome after diarrhea and appetite loss. He had suffered from nephrotic syndrome from the age of three and had been treated for five years. MR angiography showed an occlusion originating in the right internal carotid artery. The right anterior and middle cerebral arteries were imaged from the left internal carotid artery via the anterior communication artery. He showed symptoms of left hemiparesis, agnosia, loss of activity, anasarca and left hypacusis following his clinical course, but had recovered from all but left hemiparesis following medical treatments including steroid therapy. The histologic finding by a renal biopsy revealed focal glomerulosclerosis. In this case, we considered that when he was in a hypercoagulable state and had a second attack of nephrotic syndrome because of inflammation and dehydration due to diarrhea and appetite loss, his hypercoagulable state grew worse, and he then developed a cerebral infarction. When one see a patient with nephrotic syndrome, one should be attentive to the possibility of a complication of cerebral infarction. PMID- 9989359 TI - [A case of non-paralytic pontine exotropia due to brainstem infarction]. AB - A case with non-paralytic pontine exotropia due to brainstem infarction is reported. A 58-year-old male developed sudden onset diplopia. Ocular motor findings were as follows; in forward gaze, the left eye was in abduction position. Leftward gaze, the right eye did not adduct with left beating nystagmus of left eye. Rightward gaze, both eyes could make full excursion and upward, downward gaze were possible. These findings was noted at only acute phase, 7 days later NPPE was disappeared. MRI revealed spotty lesion in the paramedian portion of the mid pontine tegmentum. It is important to observe ocular movement at acute phase because NPPE is very important sign in diagnosis of brainstem disorders. PMID- 9989360 TI - [Multiple myeloma forming subcutaneous on the skull]. PMID- 9989361 TI - [A 63-year-old man with progressive cauda equina/conus medullaris syndrome]. AB - A 63-year-old man, whose father died of malignant lymphoma, developed subacutely cauda equina/conus medullaris syndrome progressed over 3 months. Initial radicular pain, ascending motor and sensory paralysis without sacral sparing, vesicorectal dysfunction were similar with signs of spinal dural arteriovenous fistula. However, mild inflammatory signs, raised serum LDH, predominantly of LDH 3, lymphocytic pleocytosis and elevated beta 2 microglobulin in CSF suggested neurolymphomatosis. It was not supported, however, after CSF immunocytochemistry, myelogram, CT, Gd-MRI and Ga scan. Spinal cord/nerve root vascular syndromes of intravascular lymphomatosis (IVL) according to Glass J et al. was suspected because of the unique neurological progression similar to Foix-Alajouanine syndrome, hypoxia without abnormalities in chest X-ray film, response to steroids and raised serum soluble IL-2 receptor. Multiple biopsies were performed with negative results. However, after all muscle biopsy confirmed IVL. The lower spinal irradiation was not effective. But CHOP regimen supplemented by granulocyte colony-stimulating factor (G-CSF) brought about swift neurological improvement and protection from late complications. Self-limiting polyneuropathy emerged during the biweekly CHOP therapy, 6 courses for 12 weeks. Eventually he was neurologically improving 10 months after the chemotherapy and adrenal enlargement, which was possibly of metastasis, was only against complete remission. This case was good outcome by biweekly CHOP using G-CSF when compared with very high mortality in reported IVL cases besides vincristine neurotoxicity under compromised blood-brain/nerve barrier due to IVL might affect the functional recovery. This case with IVL implied raised soluble IL-2 receptor and progressive cauda equina syndrome/ascending myelopathy as diagnostic clues, and efficiency of muscle biopsy to confirm IVL. PMID- 9989362 TI - Adenosine, blood pressure and NREM delta. PMID- 9989363 TI - Effects of method, duration, and sleep stage on rebounds from sleep deprivation in the rat. AB - Total sleep deprivation (TSD) of rats for 24 hours or less by continually enforced locomotion has consistently produced subsequent rebounds of slow-wave or high-amplitude EEG activity in NREM sleep, which has contributed to the widely held view that this EEG activity reflects particularly "intense" or restorative sleep. These rebounds usually have been accompanied by substantial rebounds of REM sleep. In contrast, chronic TSD (2 weeks or longer) by the disk-over-water (DOW) method has produced only huge, long-lasting rebounds of REM sleep with no rebound of high-amplitude NREM sleep. To evaluate whether the different rebounds result from different methods or from different lengths of deprivation, rats were subjected to 24-hour TSD by the DOW method. Rebounds included increases in high amplitude and slow-wave activity; i.e., the methods produced similar rebound patterns following short-term TSD. (Chronic TSD by continually enforced locomotion would be strategically difficult and severely confounded with motor fatigue.) Rats subjected to DOW-TSD for 4 days, well before the development of severe TSD symptoms, showed primarily REM sleep rebounds. Rats subjected to 1 day of selective REM sleep deprivation, but not their closely yoked control rats, showed large, significant REM sleep rebounds, which evidently were not induced by the stress of the deprivation method per se. The combined findings prompted reexamination of published evidence relevant to "sleep intensity," including "negative rebounds," rebounds in other species, the effects of stress and fatigue, depth of sleep indicators, and extended sleep. The review points out pitfalls in the designation of any specific pattern as intense sleep. PMID- 9989364 TI - Role of GABAA receptors in the regulation of sleep: initial sleep responses to peripherally administered modulators and agonists. AB - This paper reviews the sleep effects of systemically administered agonistic modulators of GABAA receptors, including barbiturates, benzodiazepines, zolpidem, zopiclone and neuroactive steroids, and the selective GABAA agonists muscimol and THIP. To assess the involvement of GABAA receptors in the physiologic regulation of sleep, the article emphasizes the hypnotic properties shared by agonistic modulators and by the selective agonists of the GABAA receptor complex. In both rats and normal sleeping individuals, agonistic modulators are able to reduce sleep latency, increase sleep continuity, and promote non-rapid-eye-movement (NREM) sleep as well as the occurrence of spindles. Furthermore, nearly all of these compounds have been shown to attenuate slow-wave activity (SWA) and to suppress the occurrence of REM sleep. In the same species, GABAA agonist(s) do not seem to affect sleep latency or REM sleep time, but may increase sleep continuity and NREM sleep and augment SWA while depressing spindle activity in humans. The distinct sleep effects of GABAA agonists may be due to their unspecific stimulation of GABAA receptors throughout the brain, and to the fact that they are poor substrates for uptake and probably exert more tonic effects than liberated GABA. If so, the involvement of GABAA receptors in the various aspects of sleep can be inferred more accurately from the hypnotic effects of agonistic modulators. This implies that an activation of GABAA receptors plays a crucial role in the initiation and maintenance of NREM sleep and in the generation of sleep spindles, but disrupts the processes underlying slow EEG components and the triggering of REM sleep. PMID- 9989365 TI - Circadian and homeostatic influences on sleep in the squirrel monkey: sleep after sleep deprivation. AB - A series of sleep deprivation (SD) experiments were performed to examine the relative influence of circadian and homeostatic factors on the timing of sleep in squirrel monkeys free-running in constant illumination. All SDs started at the beginning of subjective night and lasted 0, 1/4, 1/2, 1, 1 1/4, or 1 1/2 circadian cycles. These six lengths represented three pairs: (0.1), (1/4, 1 1/4), (1/2, 1 1/2). Within each pair, SD ended at the same circadian phase but differed by one circadian cycle in duration. Both before and after SD, consolidated sleep (CS) episodes occurred predominantly during subjective night, even after long SDs ending at the beginning of subjective day. CS duration was strongly influenced by circadian phase but had no overall correlation with prior wake duration. Sleep loss incurred during SDs longer than 1/4 cycle was only partially recovered over the next two circadian cycles, though total sleep duration was closer to baseline levels after the second circadian cycle after SD. There was a trend toward a positive correlation between prior wake duration and the amount of NREM and delta activity measures during subjective day. Delta activity was not increased in the first 2 hours of CS after the SD. Relatively high levels of delta activity occurred immediately after the SD ended and again at the time of baseline CS onset. These data indicate that the amount of sleep and delta activity after SD in squirrel monkeys is weakly dependent on prior wake duration. Circadian factors appear to dominate homeostatic processes in determining the timing, duration and content of sleep in these diurnal primates. PMID- 9989366 TI - Effect of serotonin uptake inhibition on breathing during sleep and daytime symptoms in obstructive sleep apnea. AB - Pharmacologic enhancement of serotonergic transmission by serotonin uptake inhibition has been suggested as one approach to improve upper-airway patency and thus nocturnal breathing in patients with obstructive sleep apnea (OSA). To test this hypothesis, we performed a double-blind, randomized, placebo-controlled crossover study testing the effect of paroxetine (20 mg od) on polysomnographic and psychopathologic outcomes in 20 male OSA patients (mean age 52.1 years, mean BMI 28.7 kg/m2, mean oxygen desaturation index on a previous screening 25.4/hour). The two treatment periods of 6 weeks and the separating washout period of 4 weeks were completed by 17 patients. Paroxetine reduced the apnea index during NREM sleep (-35%, p = 0.003), but not during REM sleep. No significant effect on hypopnea indices was found. With the exception of a previously described REM-postponing effect (p = 0.05), sleep architecture was not significantly influenced by paroxetine. Similarly, the effect of paroxetine on apnea was not associated with a significant overall alleviation of psychopathologic symptoms as rated on the Comprehensive Psychopathological Rating Scale or OSA-related daytime complaints assessed by visual analog scales. We conclude that enhanced serotonergic transmission improves breathing during NREM sleep in OSA. This effect is poorly related to effects on sleep architecture or daytime symptoms. PMID- 9989367 TI - Arousal threshold to respiratory stimuli in OSA patients: evidence for a sleep dependent temporal rhythm. AB - It has recently been described that the maximal respiratory effort developed at the end of an apnea (Pesmax)--which is regarded as an index of arousal threshold in patients with obstructive sleep apnea syndrome (OSA)--increases progressively during the night, probably as a consequence of associated sleep fragmentation. In order to find out whether the nocturnal trend of Pesmax may be more influenced by a sleep-dependent circadian rhythm than by sleep fragmentation, we revised the polygraphic recordings of 37 patients in whom obstructive apneas were recorded for at least 7 hours. In 15 of these patients, analysis was made for eight hours of the night. During each hour we analyzed at least 7 obstructive apneas, in which we measured the minimal esophageal pressure at the start of the apnea, the maximum value recorded at the end of the apnea (Pesmax), the difference from the minimum to the maximum (delta Pes), and the rate of increase in esophageal pressure (RPes). As indices of sleep fragmentation, we defined the number of arousals, awakenings and sleep state transitions. In the group of patients as a whole, we found a trend toward a gradual increase for apnea duration (F = 98.8, p < 0.001) and Pesmax F = 31.6, p < 0.001) which was significant from the first to the last hour. The time-dependent evolution of apnea duration and Pesmax showed that the rise in these two variables peaked during the first 3 hours of sleep, followed by a plateau and a decrease in the last hour of the night. This temporal profile was more evident when the analysis was available for 8 hours. No significant changes across the night were found for nocturnal hypoxemia and number of arousals. Considering the slope of Pesmax changes across the night, we saw that neither the apnea+hypopnea index nor the indices of sleep fragmentation affected the nocturnal trend. The present data demonstrate the presence of a nocturnal trend in arousal threshold in OSA patients independent of sleep fragmentation. The biphasic evolution of the arousal threshold may be caused by factors that influence the circadian and homeostatic processes. PMID- 9989368 TI - Validation of a cataplexy questionnaire in 983 sleep-disorders patients. AB - Our goal was to validate a self-administered narcolepsy questionnaire focusing on cataplexy. Nine hundred and eight three consecutive subjects entering the Stanford Sleep Disorder Clinic completed the questionnaire. Clinic physicians reported on the presence or absence of "clear-cut" cataplexy. Responses to 51 cataplexy-related questionnaire items were compared between subjects with clear cut cataplexy (n = 63) and all other patients (n = 920). As previously reported, a large portion of the non-narcoleptic population was found to experience muscle weakness with various intense emotions (1.8% to 18.0%) or athletic activities (26.2% to 28.8%). Factor analysis and Receiver Operating Characteristic Curve (ROC) analysis were used to determine the most predictive items for clear-cut cataplexy. Most strikingly, cataplexy was best differentiated from other types of muscle weakness when triggered by only three typical situations: "when hearing and telling a joke," "while laughing," or "when angry." Face or neck, rather than limbs, were also more specifically involved in clear-cut cataplexy. Other items, such as length of attacks, bilaterality, and alteration in consciousness, were poorly predictive. A simple decision tree was constructed to isolate high-(91.7%) and low-(0.6%) risk groups for cataplexy. This questionnaire will be used to increase diagnostic consistency across clinical centers, thus providing more homogenous subject pools for clinical and basic research studies. PMID- 9989369 TI - Limits of self-report in assessing sleep terrors in a population survey. AB - Sleep terrors are less frequent compared to other parasomnias, and there are no prevalence studies on adults. We performed a questionnaire study in a well defined population-based sample, the Finnish Twin Cohort. The study population consisted of 11,220 subjects aged 33-60 years, responding to questions on the frequency of sleep terrors in childhood and as adults. In the first questionnaire about 9% reported sleep terrors often or sometimes in childhood, and 3.5% at least once monthly as adults. However, in a second more-detailed questionnaire, only 1% of those with at-least-monthly attacks in adulthood presented with features compatible with the minimal diagnostic criteria for sleep terrors of the International Classification of Sleep Disorders. There was also a strong correlation between current occurrence of nightmares and the report of sleep terrors. Although a clinically definable entity, sleep terrors seem to be unknown to lay people, at least in Finland. Therefore, the use of single items or brief question series on sleep terrors may give inaccurate results in questionnaires. An interview of a person who has witnessed the nocturnal attack suspected to be sleep terror is essential because of the patient's impaired recall of the episode. Our results also support the general view that sleep terrors are rare in adults. PMID- 9989370 TI - Estimating sleep patterns with activity monitoring in children and adolescents: how many nights are necessary for reliable measures? AB - STUDY OBJECTIVES: This study provides estimates of reliability for aggregated values from 1 to 7 recording nights for five commonly used actigraphic measures of sleep patterns, reliability as a function of night type (weeknight or weekend night), and stability of measures over several months. DESIGN AND SETTING: Data are from three studies that obtained 7 nights of actigraph data (using Mini Motionlogger actigraphs and associated validated algorithms [ASA]) on children and adolescents living at home on self-selected sleep-wake schedules. PARTICIPANTS: Participants were 169 children aged 12-60 months, and 55 adolescents aged 11-16 years. MEASUREMENTS AND RESULTS: Up to 28% of weekly recordings may be unacceptable for analysis in young participants because of illness, technical problems, and participant noncompliance; studies aiming to collect 5 nights of actigraph data should record for at least 1 full week. Reliability estimates for values aggregated over any 5 nights were adequate (> or = .70) for sleep start time, wake minutes, and sleep efficiency. Measures of sleep minutes and sleep period were less reliable and may require 7 or more nights for estimates of stable individual differences. Reliability for 1- or 2 night aggregates were poor for all measures. We found significant and high correlations between summer and fall session measures for all five variables when weekend nights were included. CONCLUSIONS: Five or more nights of usable recordings are required to obtain reliable actigraph measures of sleep for children and adolescents. PMID- 9989371 TI - Validity of neural network in sleep apnea. AB - Clinical assessment of obstructive sleep apnea (OSA) is poor. Overnight polysomnography (OPG) is the standard reference test, but it is expensive and time-consuming. We developed an artificial neural network (ANN) using anthropomorphic measurements and clinical information to predict the apnea hypopnea index (AHI). All patients completed a questionnaire about sleep symptoms, sleep behavior, and demographic information prior to undergoing OPG. Neck circumference, height, and weight were obtained on presentation to the sleep center. Twelve variables were used as inputs. The output was an estimate of the AHI. The network was trained with a back-propagation algorithm on 189 patients and validated prospectively on 80 additional patients. Data from the derivation group was used to calculate the 95% confidence interval of the estimated AHI. Predictive accuracy at different AHI thresholds was assessed by the c-index, which is equivalent to the area under the receiver operator characteristic curve. The c-index for predicting OSA in the validation set was 0.96 +/- 0.0191 SE, 0.951 +/- 0.0203 SE, and 0.935 +/- 0.0274 SE, using thresholds of > 10, > 15, and > 20/hour respectively. The actual AHI of the 80 patients in the validation data set fell within the 95% confidence limits of the values predicted by the ANN. This study suggests that ANN may be useful as a predictive tool for OSA. PMID- 9989372 TI - Thalidomide increases both REM and stage 3-4 sleep in human adults: a preliminary study. AB - Polysomnography was used to assess the effect of thalidomide on human sleep. This compound significantly increased the time spent in REM and stage 3-4 sleep as compared with placebo. On the other hand, thalidomide significantly decreased the time spent in stage 1, while the time spent in stage 2 was unchanged. The effect of thalidomide on REM and stage 3-4 sleep is unique as compared with other hypnotics. Although the mode of action of this compound is unknown, further studies on thalidomide should help in our understanding of the mechanisms of sleep regulation. PMID- 9989373 TI - Comparison of the effects of pravastatin and lovastatin on sleep disturbance in hypercholesterolemic subjects. AB - We have studied the effects of two cholesterol-lowering medications, lovastatin and pravastatin, on different sleep parameters in hypercholesterolemic subjects. These medications are 3-hydroxy-methylglutaryl coenzyme A inhibitors. Only subjects who had complained of sleep disturbance while on previous treatment with lovastatin were enrolled. Sixteen subjects (11 men and 5 women) underwent a randomized, double-blind, three-way crossover treatment with lovastatin, pravastatin, and placebo. Each phase of the study lasted 4 weeks. A placebo wash out period of 4 weeks separated each treatment phase. At the end of each treatment phase, subjects were admitted to the sleep laboratory for 2 consecutive nights. No statistical differences were detected during treatment with lovastatin, pravastatin, and placebo for sleep parameters such as total sleep time, total awake time, wake time after sleep onset, efficiency of sleep, and percent of different phases of sleep. Our study suggests that lovastatin and pravastatin do not have a significant effect on sleep parameters in hypercholesterolemic subjects that could explain their complaints of insomnia. Nevertheless, the subjects did have moderate sleep disturbances that could account for insomnia and most likely predate the use of HMG-CoA reductase inhibitors. PMID- 9989374 TI - Bibliography of recent literature in sleep research. PMID- 9989375 TI - Rapid amperometric verification of PCR amplification of DNA. AB - Amplification of an 800-base template was verified in a 10-min test on a 2-microL sample of the PCR product solution. For verification, digoxigeninylated primers and biotinylated d-UTP-16-biotin were added to the amplification solution. The resulting amplified product was digoxigeninlabeled at its 3'-end and was also labeled with multiple biotin functions along its chain. The detecting electrode was coated with an electron-conducting redox hydrogel to which anti-digoxin monoclonal antibody was covalently bound. The amplified DNA was captured by the electrode through conjugation of its 3'-digoxigenin with the antibody. Exposure to a solution of horseradish peroxidase-labeled avidin led to capture of the enzyme and switched the redox hydrogel from a noncatalyst to catalyst for H2O2 electroreduction. The switching resulted in an H2O2 electroreduction current density of 2.1 +/- 0.9 microA cm-2 in 10-4 M H2O2 at Ag/AgCl potential and at 25 degrees C. PMID- 9989376 TI - End-column amperometric detection in capillary electrophoresis: influence of separation-related parameters on the observed half-wave potential for dopamine and catechol. AB - Capillary electrophoresis (CE) was coupled to a micro-electrode-based end-column amperometric detector. The influences of separation voltage, CE buffer concentration, and capillary-to-electrode distance on the observed hydrodynamic voltammetry of dopamine and catechol were studied using a separation capillary with an i.d. of 25 microns. It was found that an increased CE voltage, increased buffer concentration, or decreased capillary-to-electrode distance resulted in a positive shift of the observed half-wave potentials for both dopamine and catechol. At a constant separation current of 1.6 microA, the observed half-wave potential was found to increase with applied separation voltage. Furthermore, when experiments were carried out with a platinum quasi-reference electrode instead of a Ag/AgCl reference electrode, similar shifts in half-wave potential were observed. These results indicate that the observed shifts are an effect of the separation voltage rather than the separation current or a change in the reference potential. The characteristics of end-column detection with and without a fracture decoupler were compared. It was found that the effects of separation voltage, CE buffer concentration, and capillary-to-electrode distance were minimized by the use of a decoupling device. The observed half-wave potentials for dopamine and catechol were more positive when a CE capillary without a decoupler was employed compared to when a decoupler was used. Additionally, using the fracture decoupler, the observed half-wave potentials for both dopamine and catechol were approximately the same as when no CE voltage was applied (i.e., when the hydrodynamic voltammograms were recorded under flow injection conditions). PMID- 9989377 TI - Optimization of high-speed DNA sequencing on microfabricated capillary electrophoresis channels. AB - DNA sequencing separations have been performed in microfabricated electrophoresis channels with the goal of determining whether high-quality sequencing is feasible with these microdevices. The separation matrix, separation temperature, channel length and depth, injector size, and injection parameters were optimized. DNA fragment sizing separations demonstrated that 50-micron-deep channels provide the best sensitivity for our detection configuration. One-color sequencing separations of single-stranded M13mp18 DNA on 3% linear polyacrylamide (LPA) were used to optimize the twin-T injector size, injection conditions, and temperature. The best one-color separations were observed with a 250-micron twin-T injector, an injection time of 60 s, and a temperature of 35 degrees C. The first 500 bases appeared in 9.2 min with a resolution of > 0.5, and the separation extended to 700 bases. The best four-color sequencing separations were performed using 4% LPA, a temperature of 40 degrees C, and a 100-micron twin-T injector. These four color runs were complete in only 20 min, could be automatically base-called using BaseFinder to over 600 bp after the primer, and were 99.4% accurate to 500 bp. These results significantly advance the quality of microchip-based electrophoretic sequencing and indicate the feasibility of performing high-speed genomic sequencing with microfabricated electrophoretic devices. PMID- 9989378 TI - Photoionization of gas-phase versus ion-beam-desorbed dopamine with femtosecond laser pulses. AB - We have investigated the photoionization of gas-phase and ion-beam desorbed dopamine using femtosecond laser pulses at wavelengths of 800, 400, 267, and 200 nm. Photoionization of gas-phase dopamine is found to produce the molecular ion, and three fragment ions at all four wavelengths, with the branching ratios strongly wavelength dependent. Photoionization at 400 and 267 nm yields the highest molecular ion signal, while that at 800 and 200 nm produces very little molecular ion signal. An excited-state lifetime of approximately 10 ps following 267-nm excitation has been measured for dopamine using time-resolved pump-probe techniques. The short-lived excited state suggests that internal conversion, intersystem crossing, and/or dissociation is a concern when ionizing at this wavelength using longer laser pulses. Photoionization of ion-beam-desorbed dopamine exhibits a large degree of fragmentation at all four wavelengths, though 267-nm photoionization produces the highest yield of dopamine fragment ions. Power dependence studies show a high degree of internal excitation. A direct comparison of ion yields obtained for photoionization of ion-beam-desorbed dopamine at 267 nm to that for SIMS shows a 20-fold increase in signal. PMID- 9989379 TI - A dynamical investigation of acrylodan-labeled mutant phosphate binding protein. AB - The static and dynamical behavior of a fluorescently labeled mutant of the Escherichia coli periplasmic phosphate binding protein (PBP) was investigated through steady-state and time-resolved fluorescence spectroscopy. As a means of developing a biorecognition element for inorganic phosphate (P(i)), alanine-197 of PBP was replaced with a cysteine. This site was then labeled with an environmentally sensitive fluorophore. The fluorescence emission of the mutant PBP labeled with acrylodan (MPBP-AC) proved to be sensitive to micromolar concentrations of P(i), as indicated by a 50% increase in the steady-state emission intensity. Steady-state results indicated that the labeling protocol was specific for cys-197 only and did not label the wild-type PBP; thus, a site selective labeling protocol was developed. Time-resolved measurements were used to determine the influence of the dynamics of MPBP-AC on the process of signal transduction. Time-resolved anisotropy measurements revealed that rotational dynamics were best described by a model with two independent motions: the global motion of the protein and the local motion of the acrylodan probe. The rates of both global and local rotational reorientation of MPBP-AC were faster when the protein was P(i)-bound rather than P(i)-free. This was a result of structural changes involving or surrounding both the P(i)-binding site (global changes) and the residues in near proximity to the fluorescent reporter group (local changes). Recovery of the semiangle (theta) indicated that local structural changes in MPBP AC took place when P(i) was bound to the protein. Acrylodan gained mobility when MPBP-AC bound P(i), as indicated by the fact that theta increased by approximately 5 degrees. In addition, dynamic quenching measurements confirmed that structural changes occurred locally near the cys-197. Acrylodan became more accessible to iodide when MPBP-AC bound P(i), as demonstrated by the 35% increase in the value of the bimolecular quenching constant. PMID- 9989380 TI - Differentiation of microorganisms based on pyrolysis-ion trap mass spectrometry using chemical ionization. AB - The ability to differentiate microorganisms using pyrolysision trap mass spectrometry was demonstrated for five Gram-negative disease-causing organisms: Brucella melitensis, Brucella suis, Vibrio cholera, Yersinia pestis, and Francisella tularensis. Bacterial profiles were generated for gamma-irradiated bacterial samples using pyrolytic methylation and compared for electron ionization and chemical ionization using several liquid reagents with increasing proton affinities. Electron ionization combined with pyrolysis caused extensive fragmentation, resulting in a high abundance of lower mass ions and diminishing the diagnostic value of the technique for compound identification and bacterial profiling. Chemical ionization reduced the amount of fragmentation due to ionization while enhancing the molecular ion region of the fatty acids. As the proton affinity of the reagent increased, the protonated molecular ions of the fatty acids became the predominant ions observed in the mass spectrum. As a result, chemical ionization was shown to be more effective than electron ionization in bacterial profiling. Whereas the bacteria could be distinguished at the Genera level using electron ionization, further differentiation to the subspecies level was possible using chemical ionization. The greatest separation among the five test organisms, in terms of Euclidean distances, was obtained using ethanol as the chemical ionization reagent and using pooled masses representing specific fatty acid biomarkers rather than total ion profiles. PMID- 9989381 TI - Characterization of proteins from human cerebrospinal fluid by a combination of preparative two-dimensional liquid-phase electrophoresis and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. AB - To purify and characterize low-abundance proteins in complex biological mixtures, we used a novel strategy that combined preparative two-dimensional liquid-phase electrophoresis (2D-LPE) and matrix-assisted laser desorption/ionization time-of flight mass spectrometry (MALDI-TOF MS). Preparative 2D-LPE is based on the same isoelectric focusing and gel electrophoresis principles as the widely used analytical 2D gel electrophoresis, except that analytes remain in solution throughout separation. This novel approach shows many improvements compared to analytical 2D gel electrophoresis for the separation of proteins in biological fluids. For example, larger volumes/amounts of samples can be loaded, yielding sufficient amounts of low-abundance proteins for further characterization. Since proteins remain in liquid phase during the entire procedure, extra steps such as electroelution, extraction, or transfer to membranes from the gels prior to mass spectrometric analysis are obviated. We report the usefulness of 2D-LPE combined with MALDI-TOF MS for the purification and characterization of cystatin C and beta-2 microglobulin in human cerebrospinal fluid. This method should be applicable to a wide range of biological fluids, such as cerebrospinal fluid, serum, tissue extracts, cell media, whole cells, and bacterial lysates. PMID- 9989382 TI - Liquid-liquid extraction of cadmium by sodium diethyldithiocarbamate from biological matrixes for isotope dilution inductively coupled plasma mass spectrometry. AB - A published procedure for the liquid-liquid extraction of Cd by sodium diethyldithiocarbamate (NaDDC) was modified and tested on 12 biological matrixes of plant and animal origin for use with isotope dilution (ID) inductively coupled plasma mass spectrometry (ICPMS). The tested matrixes were reference materials, certified for Cd, and a feces in-house standard. The digested and extracted standards were analyzed for Cd stable isotopes by ICPMS and the resulting isotope ratios examined for isobaric and polyatomic interferences. Cadmium recoveries, after extraction, ranged from 73% to 20% and apparently were inversely related to Cd concentration, even in the presence of excess chelator. For each reference material, the measured isotope ratios for Cd were corrected for instrumental bias and compared to natural abundance Cd isotope ratios. Nonextracted samples had large isotope ratio deviations for all but one or two ratios. Extraction improved all the isotope ratios measured (lowered % error relative to natural abundances), but interferences were noted for a few samples. The extracted human in-house feces standard was found to have Sn signals reduced by 300-fold, but residual Sn concentrations still interfered with 116Cd, though not 112Cd or 114Cd. Thus, evaluation of the NADDC-extracted in-house fecal standard and reference materials indicate the successful removal of interferences that otherwise prevented accurate determinations of Cd by IDICPMS and show that a number of Cd isotope ratios could be accurately measured (< 1.5% error) for multiple stable isotope tracer studies in a broad range of NaDDC-extracted biological matrixes. PMID- 9989383 TI - Direct sequencing of neuropeptides in biological tissue by MALDI-PSD mass spectrometry. AB - Dissected tissue pieces of the pituitary pars intermedia from the amphibian Xenopus laevis was directly subjected to matrix-assisted laser desorption/ionization (MALDI) mass analysis. The obtained MALDI peptide profile revealed both previously known and unexpected processing products of the proopiomelanocortin gene. Mass spectrometric peptide sequencing of a few of these neuropeptides was performed by employing MALDI combined with postsource decay (PSD) fragment ion mass analysis. The potential of MALDI-PSD for sequence analysis of peptides directly from unfractionated tissue samples was examined for the first time for the known desacetyl-alpha-MSH-NH2 and the presumed vasotocin neuropeptide. In addition, the sequence of an unknown peptide which was present in the pars intermedia tissue sample at mass 1392.7 u was determined. The MALDI PSD mass spectrum of precursor ion 1392.7 u contained sufficient structural information to uniquely identify the sequence by searching protein sequence databases. The determined amino acid sequence corresponds to the vasotocin peptide with a C-terminal extension of Gly-Lys-Arg ("vasotocinyl-GKR"), indicating incomplete processing of the vasotocin precursor protein in the pituitary pars intermediate of X. laevis. Both vasotocin and vasotocinyl-GKR are nonlinear peptides containing a disulfide (S-S) bridge between two cysteine residues. Interpretation of the spectra of these two peptides reveals three different forms of characteristic fragment ions of the cysteine side chain: peptide-CH2-SH (regular mass of Cys-containing fragment ions), peptide-CH2-S-SH (regular mass + 32 u) and peptide = CH2 (regular mass -34 u) due to cleavage on either side of the sulfur atoms. PMID- 9989384 TI - Ultrasensitive detection of closely related angiotensin I peptides using capillary electrophoresis with near-infrared laser-induced fluorescence detection. AB - A novel near-infrared (NIR) fluorescent dye (NN382, LICOR, Inc.) was evaluated as an ultrasensitive peptide-labeling reagent for use with capillary electrophoresis (CE). Six angiotensin I (Ang-I) variants were selected as model peptides for the derivatization and separation studies. The closely related decapeptides were labeled with the NIR dye, separated using CE, and detected by NIR laser-induced fluorescence. Derivatization of the peptides was achieved under aqueous conditions using 2.5-500 pmol of Ang-I in a 50-microL sample (5 x 10(-8)-1 x 10( 5)M), and between 1.3 and 254 amol of the labeled peptides were injected on column. The fluorescence response was linear over a 200-fold range (correlation r > or = 0.9986). The limit of detection (SNR = 3, signal/RMS noise) ranged from 100 to 300 zmol, for the six Ang-I variants. Four of six peptides were resolved from each other and excess dye using capillary zone electrophoresis with a simple 50 mM phosphate run buffer, pH 7.2. Two pairs of coeluting peptides were successfully resolved using micellar electrokinetic chromatography with a nonionic surfactant, Triton X-100. The NIR amine-labeling reagent NN382 is a viable alternative to using visible fluorophores for CE methods requiring high sensitivity. PMID- 9989385 TI - Adaptation of capillary isoelectric focusing to microchannels on a glass chip. AB - As a first step toward adaptation of capillary isoelectric focusing (cIEF) to microchannels on a glass chip, we have compared the three most common mobilization methods: chemical, hydrodynamic, and electroosmotic flow (EOF) driven mobilization. Using a commercial cIEF apparatus with coated or uncoated fused-silica capillaries, both chemical and hydrodynamic mobilization gave superior separation efficiency and reproducibility. However, EOF-driven mobilization, which occurs simultaneously with focusing, proved most suitable for miniaturization because of high speed, EOF compatibility and low instrumentation requirements. When this method was tested in a 200-micron-wide, 10-micron-deep, and 7-cm-long channel etched into planar glass, a mixture of Cy5-labeled peptides could be focused in less than 30 s, with plate heights of 0.4 micron (410 plates/s) upon optimization. For a total analysis time of less than 5 min, we estimate a maximum peak capacity of approximately 30-40. Interestingly, the order of migration was found to be reversed compared to capillary-based focusing. PMID- 9989386 TI - Ultrahigh-pressure reversed-phase capillary liquid chromatography: isocratic and gradient elution using columns packed with 1.0-micron particles. AB - Fused-silica capillaries with inner diameters of 33 microns and lengths of 25-50 cm are slurry-packed with 1.0-micron nonporous octadecylsilane-modified (C18) silica spheres. These columns are used to perform ultrahigh-pressure reversed phase liquid chromatographic analyses in both isocratic and gradient elution modes. Mobile-phase pressures as high as 5000 bar (72,000 psi) are applied to column inlets to generate more than 200,000 theoretical plates in 6 min (k' approximately 1) for small, organic analytes. Average capacity factors of analytes are found to increase linearly with applied pressure. An electrically driven constant-flow syringe pump capable of generating mobile-phase pressures as high as 9000 bar (130,000 psi) is described. This pump is used in conjunction with an exponential dilution method for the gradient separation of peptides from a tryptic digest on a 27-cm-long capillary packed with 1.0-micron particles. A peak capacity of 300 is demonstrated for a 30-min analysis. PMID- 9989387 TI - Automated measurement of peak widths for the determination of peak capacity in complex chromatograms. AB - The peak capacity was measured for an ultrahigh-pressure gradient elution chromatogram of a fluorescently tagged tryptic digest of ovalbumin. The peak widths in the chromatogram were determined by measuring the peak height and the second derivative at the peak maximum. This approach for measuring peak widths was programmed into a computer, and the software accurately determined the general progression of peak widths by measuring 47 peaks throughout the chromatogram in under 10 s. Peak capacity was determined by taking the definite integral of the plot of reciprocal base peak width versus retention time. This calculation of peak capacity is a linear transformation with respect to separation space, so the method is more rigorously accurate than previous methods. The peak capacity for the chromatogram was calculated to be 316. PMID- 9989388 TI - ESR and HPLC-EC analysis of the interaction of hydroxyl radical with DMSO: rapid reduction and quantification of POBN and PBN nitroxides. AB - The low stability of hydroxyl radical (OH.)-derived nitroxides is a limiting factor for direct spin-trapping of OH. in biological systems. The latter experimental difficulty is partly solved with the introduction of dimethyl sulfoxide (DMSO) into the studied systems. Hydroxyl radical oxidizes DMSO to methyl radical, which forms relatively stable nitroxides. The results of the present work provide evidence that in alpha-(4-pyridyl-1-oxide)-N-tert butylnitrone (POBN) and alpha-phenyl-N-tert-butylnitrone (PBN) spin-trapping experiments aimed to detect methyl radical in biological systems, the nitroxides formed can be reduced to their ESR-"silent" hydroxylamine derivatives. The nitroxides and their hydroxylamine derivatives were successfully analyzed by HPLC with electrochemical (EC) and UV detection. The lowest limits of UV and EC detection of POBN/CH3 hydroxylamine was evaluated to be in the micro- and nanomolar range, respectively. In parallel ESR and HPLC-EC analysis of the metabolism of menadione by either HepG2 cells or isolated rat hepatocytes in the presence of DMSO, the HPLC-EC method has proven to be more sensitive in detecting the production of methyl radical. The use of the HPLC-EC detection of POBN/CH3 and PBN/CH3 is expected to be advantageous in detection of hydroxyl radical in biological systems in the presence of DMSO. PMID- 9989389 TI - Isotope dilution analysis of bromate in drinking water matrixes by ion chromatography with inductively coupled plasma mass spectrometric detection. AB - Bromate is a disinfection byproduct in drinking water which is formed during the ozonation of source water containing bromide. This paper describes the analysis of bromate via ion chromatography-inductively coupled plasma mass spectrometry. The separation of bromate from interferences such as bromide and brominated haloacetic acids is achieved using a PA-100 column in combination with a 5 mM HNO3 + 25 mM NH4NO3 mobile phase. Polyatomic ions are observed on masses 79 and 81 in a synthetic phosphate matrix and in ozonated drinking waters. These polyatomic ions have been tentatively identified as PO3+ and H2PO3+. These polyatomic ions do not interfere with the detection of bromate because phosphate elutes prior to bromate. A polyatomic ion is observed on mass 81 in a synthetic sulfate matrix and in ozonated drinking waters. This polyatomic ion has been tentatively identified as HSO3+ and does not interfere with the detection of bromate because sulfate elutes after bromate. Isotope dilution analysis produces a relative standard deviation (RSD) of approximately 5% for both enriched isotopic additions at sample concentrations of 10 ng/g. The RSD associated with the direct analysis of bromate is 3.2% at sample concentrations of 10 ng/g. The bromate concentrations determined in ozonated drinking waters via isotope dilution analysis are within 10% of the concentrations determined via direct analysis for sample concentrations above 2 ng/g. The detection limit for the direct analysis of bromate via IC-ICPMS is 0.3 ng/g. PMID- 9989390 TI - Full second-order chromatographic/spectrometric data matrices for automated sample identification and component analysis by non-data-reducing image analysis. AB - A data analysis method is proposed for identification and for confirmation of classification schemes, based on single- or multiple-wavelength chromatographic profiles. The proposed method works directly on the chromatographic data without data reduction procedures such as peak area or retention index calculation. Chromatographic matrices from analysis of previously identified samples are used for generating a reference chromatogram for each class, and unidentified samples are compared with all reference chromatograms by calculating a resemblance measure for each reference. Once the method is configured, subsequent sample identification is automatic. As an example of a further development, it is shown how the method allows identification of characteristic sample components by local similarity calculations thus finding common components within a given class as well as component differences between classes from the reference chromatograms. This feature is a valuable aid in selecting components for further analysis. The identification method is demonstrated on two data sets: 212 isolates from 41 food borne Penicillium species and 61 isolates from 6 soil-borne Penicillium species. Both data sets yielded over 90% agreement with accepted classifications. The method is highly accurate and may be used on all sorts of chromatographic profiles. Characteristic component analysis yielded results in good agreement with existing knowledge of characteristic components, but also succeeded in identifying new components as being characteristic. PMID- 9989391 TI - Determination of trans-resveratrol in plasma by HPLC. AB - trans-Resveratrol (trans-3,5,4'-trihydroxystilbene), a phenolic compound present in grapes, wines, and peanuts, has been reported to have health benefits including anticarcinogenic effects and protection against cardiovascular diseases. Despite its importance, little is known about its bioavailability in both humans and animals. A fundamental step for this evaluation consisted in measuring this stilbene in blood. In the present work, a simple and rapid HPLC method with diode array-UV detection has been developed. Resveratrol contained in plasma was purified by solid-phase extraction using a C18 cartridge. The sample was rinsed with water and methanol-water (25:75 v/v), and trans-resveratrol was finally eluted with methanol. The collected fraction was evaporated under nitrogen and analyzed by HPLC. The method was validated by obtaining a linear correlation, a detection limit of 20 micrograms/L, and a good precision with a coefficient of variation of 2.85%. trans-Resveratrol administered orally to rats was detected in plasma. With this procedure, excellent separation of trans resveratrol is achieved, thus allowing a rapid analysis of the sample for absorption, distribution, and metabolism studies. PMID- 9989392 TI - Application of multilayer feed-forward neural networks to automated compound identification in low-resolution open-path FT-IR spectrometry. AB - A drawback of current open-path Fourier transform infrared (OP/FT-IR) systems is that they need a human expert to determine those compounds that may be quantified from a given spectrum. In this work, multilayer feed-forward neural networks with one hidden layer were used to automatically recognize compounds in an OP/FT-IR spectrum without compensation of absorption lines due to atmospheric H2O and CO2. The networks were trained by fast-back-propagation. The training set comprised spectra that were synthesized by digitally adding randomly scaled reference spectra to actual open-path background spectra measured over a variety of path lengths and temperatures. The reference spectra of 109 compounds were used to synthesize the training spectra. Each neural network was trained to recognize only one compound in the presence of up to 10 other interferences in an OP/FT-IR spectrum. Every compound in a database of vaporphase reference spectra can be encoded in an independent neural network so that a neural network library can be established. When these networks are used for the identification of compounds, the process is analogous to spectral library searching. The effect of learning rate and band intensities on the convergence of network training was examined. The networks were successfully used to recognize five alcohols and two chlorinated compounds in field-measured controlled-release OP/FT-IR spectra of mixtures of these compounds. PMID- 9989393 TI - Hot seat in the kitchen. PMID- 9989394 TI - Harvard reveals plans for research centres. PMID- 9989395 TI - Fear of BSE risks could hit US blood banks. PMID- 9989396 TI - Tougher EU copyright rules come under fire. PMID- 9989397 TI - Risks inherent in fetal gene therapy. PMID- 9989398 TI - Visible viruses and geodesic domes. PMID- 9989399 TI - Can teaching ethics make people ethical? PMID- 9989400 TI - From Pan to pandemic. PMID- 9989401 TI - Apoptosis. A cellular poison cupboard. PMID- 9989402 TI - Neurobiology. Striving for coherence. PMID- 9989403 TI - UV-B damage amplified by transposons in maize. PMID- 9989404 TI - Female development in mammals is regulated by Wnt-4 signalling. AB - In the mammalian embryo, both sexes are initially morphologically indistinguishable: specific hormones are required for sex-specific development. Mullerian inhibiting substance and testosterone secreted by the differentiating embryonic testes result in the loss of female (Mullerian) or promotion of male (Wolffian) reproductive duct development, respectively. The signalling molecule Wnt-4 is crucial for female sexual development. At birth, sexual development in males with a mutation in Wnt-4 appears to be normal; however, Wnt-4-mutant females are masculinized-the Mullerian duct is absent while the Wolffian duct continues to develop. Wnt-4 is initially required in both sexes for formation of the Mullerian duct, then Wnt-4 in the developing ovary appears to suppress the development of Leydig cells; consequently, Wnt-4-mutant females ectopically activate testosterone biosynthesis. Wnt-4 may also be required for maintenance of the female germ line. Thus, the establishment of sexual dimorphism is under the control of both local and systemic signals. PMID- 9989405 TI - Hybrid hydrogels assembled from synthetic polymers and coiled-coil protein domains. AB - Stimuli-sensitive polymer hydrogels, which swell or shrink in response to changes in the environmental conditions, have been extensively investigated and used as 'smart' biomaterials and drug-delivery systems. Most of these responsive hydrogels are prepared from a limited number of synthetic polymers and their derivatives, such as copolymers of (meth)acrylic acid, acrylamide and N-isopropyl acrylamide. Water-soluble synthetic polymers have also been crosslinked with molecules of biological origin, such as oligopeptides and oligodeoxyribonucleotides, or with intact native proteins. Very often there are several factors influencing the relationship between structure and properties in these systems, making it difficult to engineer hydrogels with specified responses to particular stimuli. Here we report a hybrid hydrogel system assembled from water-soluble synthetic polymers and a well-defined protein-folding motif, the coiled coil. These hydrogels undergo temperature-induced collapse owing to the cooperative conformational transition of the coiled-coil protein domain. This system shows that well-characterized water-soluble synthetic polymers can be combined with well-defined folding motifs of proteins in hydrogels with engineered volume-change properties. PMID- 9989406 TI - A complex clathrate hydrate structure showing bimodal guest hydration. AB - Interactions between hydrophobic groups in water, as well as biomolecular hydration more generally, are intimately connected to the structure of liquid water around hydrophobic solutes. Such considerations have focused interest on clathrate hydrates: crystals in which a hydrogen-bonded network of water molecules encages hydrophobic guest molecules with which the water interacts only by non-directional van der Waals forces. Three structural families of clathrate hydrates have hitherto been recognized: cubic structure I (2M(S)-6M(L) x 46H2O), cubic structure II (16M(S) x 8M(L)-136H2O) and hexagonal structure H (M(L) x 3M(S) x 2M(S) x 34H2O) hydrates (here M(L) and M(S) are the hydrophobic guest sites associated with large and small cavities, respectively). Here we report a new hydrate structure: 1.67 choline hydroxide-tetra-n-propylammonium fluoride x 30.33H2O. This structure has a number of unusual features; in particular the choline guest exhibits both hydrophobic and hydrophilic modes of hydration. Formally the structure consists of alternating stacks of structure H and structure II hydrates, and might conceivably be found in those settings (such as seafloor deposits over natural-gas fields) in which clathrate hydrates form naturally. PMID- 9989407 TI - A neuronal representation of the location of nearby sounds. AB - Humans can accurately perceive the location of a sound source-not only the direction, but also the distance. Sounds near the head, within ducking or reaching distance, have a special saliency. However, little is known about this perception of auditory distance. The direction to a sound source can be determined by interaural differences, and the mechanisms of direction perception have been studied intensively; but except for studies on echolocation in the bat, little is known about how neurons encode information on auditory distance. Here we describe neurons in the brain of macaque monkeys (Macaca fascicularis) that represent the auditory space surrounding the head, within roughly 30 cm. These neurons, which are located in the ventral premotor cortex, have spatial receptive fields that extend a limited distance outward from the head. PMID- 9989408 TI - Perception's shadow: long-distance synchronization of human brain activity. AB - Transient periods of synchronization of oscillating neuronal discharges in the frequency range 30-80 Hz (gamma oscillations) have been proposed to act as an integrative mechanism that may bring a widely distributed set of neurons together into a coherent ensemble that underlies a cognitive act. Results of several experiments in animals provide support for this idea. In humans, gamma oscillations have been described both on the scalp (measured by electroencephalography and magnetoencephalography) and in intracortical recordings, but no direct participation of synchrony in a cognitive task has been demonstrated so far. Here we record electrical brain activity from subjects who are viewing ambiguous visual stimuli (perceived either as faces or as meaningless shapes). We show for the first time, to our knowledge, that only face perception induces a long-distance pattern of synchronization, corresponding to the moment of perception itself and to the ensuing motor response. A period of strong desynchronization marks the transition between the moment of perception and the motor response. We suggest that this desynchronization reflects a process of active uncoupling of the underlying neural ensembles that is necessary to proceed from one cognitive state to another. PMID- 9989409 TI - Coherence of gamma-band EEG activity as a basis for associative learning. AB - Different regions of the brain must communicate with each other to provide the basis for the integration of sensory information, sensory-motor coordination and many other functions that are critical for learning, memory, information processing, perception and the behaviour of organisms. Hebb suggested that this is accomplished by the formation of assemblies of cells whose synaptic linkages are strengthened whenever the cells are activated or 'ignited' synchronously. Hebb's seminal concept has intrigued investigators since its formulation, but the technology to demonstrate its existence had been lacking until the past decade. Previous studies have shown that very fast electroencephalographic activity in the gamma band (20-70 Hz) increases during, and may be involved in, the formation of percepts and memory, linguistic processing, and other behavioural and perceptual functions. We show here that increased gamma-band activity is also involved in associative learning. In addition, we find that another measure, gamma-band coherence, increases between regions of the brain that receive the two classes of stimuli involved in an associative-learning procedure in humans. An increase in coherence could fulfil the criteria required for the formation of hebbian cell assemblies, binding together parts of the brain that must communicate with one another in order for associative learning to take place. In this way, coherence may be a signature for this and other types of learning. PMID- 9989410 TI - Origin of HIV-1 in the chimpanzee Pan troglodytes troglodytes. AB - The human AIDS viruses human immunodeficiency virus type 1 (HIV-1) and type 2 (HIV-2) represent cross-species (zoonotic) infections. Although the primate reservoir of HIV-2 has been clearly identified as the sooty mangabey (Cercocebus atys), the origin of HIV-1 remains uncertain. Viruses related to HIV-1 have been isolated from the common chimpanzee (Pan troglodytes), but only three such SIVcpz infections have been documented, one of which involved a virus so divergent that it might represent a different primate lentiviral lineage. In a search for the HIV-1 reservoir, we have now sequenced the genome of a new SIVcpzstrain (SIVcpzUS) and have determined, by mitochondrial DNA analysis, the subspecies identity of all known SIVcpz-infected chimpanzees. We find that two chimpanzee subspecies in Africa, the central P. t. troglodytes and the eastern P. t. schweinfurthii, harbour SIVcpz and that their respective viruses form two highly divergent (but subspecies-specific) phylogenetic lineages. All HIV-1 strains known to infect man, including HIV-1 groups M, N and O, are closely related to just one of these SIVcpz lineages, that found in P. t. troglodytes. Moreover, we find that HIV-1 group N is a mosaic of SIVcpzUS- and HIV-1-related sequences, indicating an ancestral recombination event in a chimpanzee host. These results, together with the observation that the natural range of P. t. troglodytes coincides uniquely with areas of HIV-1 group M, N and O endemicity, indicate that P. t. troglodytes is the primary reservoir for HIV-1 and has been the source of at least three independent introductions of SIVcpz into the human population. PMID- 9989411 TI - Molecular characterization of mitochondrial apoptosis-inducing factor. AB - Mitochondria play a key part in the regulation of apoptosis (cell death). Their intermembrane space contains several proteins that are liberated through the outer membrane in order to participate in the degradation phase of apoptosis. Here we report the identification and cloning of an apoptosis-inducing factor, AIF, which is sufficient to induce apoptosis of isolated nuclei. AIF is a flavoprotein of relative molecular mass 57,000 which shares homology with the bacterial oxidoreductases; it is normally confined to mitochondria but translocates to the nucleus when apoptosis is induced. Recombinant AIF causes chromatin condensation in isolated nuclei and large-scale fragmentation of DNA. It induces purified mitochondria to release the apoptogenic proteins cytochrome c and caspase-9. Microinjection of AIF into the cytoplasm of intact cells induces condensation of chromatin, dissipation of the mitochondrial transmembrane potential, and exposure of phosphatidylserine in the plasma membrane. None of these effects is prevented by the wide-ranging caspase inhibitor known as Z VAD.fmk. Overexpression of Bcl-2, which controls the opening of mitochondrial permeability transition pores, prevents the release of AIF from the mitochondrion but does not affect its apoptogenic activity. These results indicate that AIF is a mitochondrial effector of apoptotic cell death. PMID- 9989412 TI - The transcriptional cofactor complex CRSP is required for activity of the enhancer-binding protein Sp1. AB - Activation of gene transcription in metazoans is a multistep process that is triggered by factors that recognize transcriptional enhancer sites in DNA. These factors work with co-activators to direct transcriptional initiation by the RNA polymerase II apparatus. One class of co-activator, the TAF(II) subunits of transcription factor TFIID, can serve as targets of activators and as proteins that recognize core promoter sequences necessary for transcription initiation. Transcriptional activation by enhancer-binding factors such as Sp1 requires TFIID, but the identity of other necessary cofactors has remained unknown. Here we describe a new human factor, CRSP, that is required together with the TAF(II)s for transcriptional activation by Sp1. Purification of CRSP identifies a complex of approximate relative molecular mass 700,000 (M(r) approximately 700K) that contains nine subunits with M(r) values ranging from 33K to 200K. Cloning of genes encoding CRSP subunits reveals that CRSP33 is a homologue of the yeast mediator subunit Med7, whereas CRSP150 contains a domain conserved in yeast mediator subunit Rgr1. CRSP p200 is identical to the nuclear hormone-receptor co activator subunit TRIP2/PBP. CRSPs 34, 77 and 130 are new proteins, but the amino terminus of CRSP70 is homologous to elongation factor TFIIS. Immunodepletion studies confirm that these subunits have an essential cofactor function. The presence of common subunits in distinct cofactor complexes suggests a combinatorial mechanism of co-activator assembly during transcriptional activation. PMID- 9989413 TI - Clinicopathological variables and p53 overexpression as a combined prognosticator for hematogenic recurrence in colorectal cancer. AB - BACKGROUND AND OBJECTIVE: Precise evaluation of the prognostic factors for hematogenic recurrence after resection for colorectal cancer is important not only for the prediction of patient outcome but also for the determination of adjuvant therapy. The purpose of the current study was to elucidate the clinical significance of using clinicopathological variables in combination with p53 expression as a prognosticator for hematogenic recurrence. METHODS: One hundred forty-two patients with colorectal cancer were examined. The expression of p53 was determined by immunohistochemical staining. RESULTS: Eighteen (60%) of the 30 patients who were positive for both p53 overexpression and lymph node metastasis, 13 (41%) of the 32 patients who were positive for p53 and venous invasion, and 13 (39%) of the 33 patients who were positive for p53 and carcinoembryonic antigen (CEA) developed hematogenic recurrence. CONCLUSIONS: The combination of p53 overexpression and lymph node metastasis was an excellent prognostic indicator for hematogenic recurrence in colorectal cancer. PMID- 9989414 TI - Clinical picture, response to therapy, and survival of women with diffuse malignant peritoneal mesothelioma. AB - BACKGROUND AND OBJECTIVE: The clinical picture, response to therapy, and prognosis of women with diffuse malignant peritoneal mesotheliomas (DMPM) are ill defined. The purpose of this study is to report on the clinical picture, response to therapy, and survival of women with DMPM. METHODS: The study is a retrospective review of 15 women with the confirmed pathologic diagnosis of DMPM treated between 1964 and 1996. Survival curves were constructed according to the Kaplan-Meier method. The effect of different factors on survival was studied using the log-rank test. Two-tailed P values < 0.05 were considered significant. RESULTS: Clinical features included abdominal distension (11/15, 73%), abdominal pain (6/15, 40%), ascites (9/15, 60%), abdominal or pelvic masses (14/15, 93%), elevated CA-125 (4/4, 100%), thrombocytosis (4/ 15, 27%), and thrombo-embolic manifestations (3/15, 20%). The response rate to all first-line chemotherapy regimens was 30%. The response rate to paclitaxel/cisplatin was 66.7% and the toxicity was tolerable. The median survival of all patients was 12.5 months. Patients who underwent cytoreductive surgery survived longer than those who underwent biopsy only (median survival 13.5 vs. 6.0 months, P = 0.24). Patients who received chemotherapy survived significantly longer than those who did not receive chemotherapy (29.0 vs. 1.0 months, P = 0.03). Patients who responded to first-line chemotherapy survived significantly longer than those who did not respond (P = 0.04). CONCLUSIONS: Cytoreductive surgery and chemotherapy, especially with paclitaxel and cisplatin, might be of benefit in women with DMPM. PMID- 9989415 TI - Clinical observations of axillary involvement for tubular, lobular, and ductal carcinomas of the breast. AB - BACKGROUND AND OBJECTIVES: Recently, there has been much interest in identifying primary breast cancer characteristics which have predictive value for axillary metastases. We studied breast cancer patients to determine variables associated with the incidence/extent of axillary involvement and to construct a modeled analysis. METHODS: Patients with invasive ductal, lobular, and tubular breast cancer (group 1, n = 15,719) were analyzed by tumor size and histology for the probability/extent of axillary metastases. A subgroup of patients was analyzed separately for any association of axillary involvement and other variables (group 2). RESULTS: In group 1, the incidence and extent (number of positive lymph nodes) of axillary metastases correlated significantly with histology and increasing tumor size of ductal and lobular histologies. Significant associations for < or = 10% axillary involvement in group 2 were age and S phase for tubular histology and differentiation for ductal histology. In a multivariate analysis, increasing tumor size was the only statistically significant correlate for axillary involvement (group 2) and for increasing number of positive nodes (group 1). CONCLUSIONS: A multivariate model of tumor size and age combined with staging techniques can successfully confirm or assess extent of axillary metastases in breast carcinoma. PMID- 9989416 TI - Reduced connexin43 expression in high-grade human brain glioma cells. AB - BACKGROUND AND OBJECTIVES: Connexin43 (cx43), a gap junction protein, is implicated in the suppression of tumor cell growth. Numerous cancer cells show a reduction or loss of cx43 expression compared to their normal counterparts. Our previous studies suggest that cx43 expression is decreased in a variety of human brain tumor cell lines. To further investigate the role of cx43 in the development of human gliomas, we performed the present study on human glioma grades I-IV. METHODS: Immunohistochemistry was performed on paraffin-embedded tissue sections of 18 human gliomas to analyze the expression levels of cx43 in different stages of human gliomas. RESULTS: High levels of cx43 were observed in all normal brain tissue and in glioma grades I and II. In contrast, the expression of cx43 was very weak in grade III gliomas and almost undetectable in grade IV gliomas. CONCLUSIONS: Our data support the hypothesis that reduction of cx43 is involved in the progression of human gliomas. PMID- 9989417 TI - Concurrent chemotherapy (5-fluorouracil and cisplatin) and radiation therapy followed by surgery for T4 squamous cell carcinoma of the esophagus. AB - BACKGROUND AND OBJECTIVES: Since the prognosis of patients with T4 squamous cell carcinoma (SCC) of the esophagus is extremely poor, an effective multimodal treatment needs to be established. METHODS: Forty-five patients with SCC of the esophagus at the T4 classification of the disease but no hematogenous metastasis were treated with concurrent chemoradiation therapy followed by surgical resection. Twenty-eight patients were treated with a regimen (protocol A) of 5 fluorouracil 750 mg/m2 on days 1-5 and 22-26, and cisplatin 70 mg/m2 on days 1 and 22. The remaining 17 patients were treated with a modified regimen (protocol B) of 5-fluorouracil 400 mg/m2 and cisplatin 10 mg/m2 on days 1-5, 8-12, 15-19, and 22-26. Radiation was delivered daily for 5 days/week for 4 weeks at the rate of 2 Gy/day to a total dose of 40 Gy in both protocols. RESULTS: A major clinical response was observed in 29 [3 complete response (CR) and 26 partial response (PR)] patients (64.4%). Twenty-eight patients (62.2%) underwent esophagectomy with no postoperative death. The median survival time of the resected patients (959 days) was significantly longer than that of the non-resected patients (178 days). Protocol B showed significantly higher pathologic effectiveness than protocol A. The pathologic CR rate for the main tumors was 1 (6.3%) of 16 patients for protocol A and 7 (58.3%) of 12 patients for protocol B. The pathologic CR rate for metastasized lymph nodes was 4/11 (36.4%) for protocol A and 5/5 (100%) for protocol B. Good histological response of the main tumors correlated well with long survival. The treatments were well tolerated except for one treatment-related death. CONCLUSIONS: Concurrent chemoradiation therapy followed by surgery is an effective and safe multimodal therapy for patients with primary inoperable T4 SCC of the esophagus. PMID- 9989418 TI - Irradiation of the tumor bed alone after lumpectomy in selected patients with early-stage breast cancer treated with breast conserving therapy. AB - BACKGROUNDS AND OBJECTIVES: We present the interim findings of our in-house protocol treating the tumor bed alone after lumpectomy with low-dose-rate (LDR) interstitial brachytherapy in selected patients with early-stage breast cancer treated with breast conserving therapy (BCT). METHODS: From 1 March 1993 through 1 January 1995, 50 women with early-stage breast cancer were entered into a protocol of tumor bed irradiation alone using an interstitial LDR implant. Patients were eligible if their tumor was an infiltrating ductal carcinoma < or =3 cm in diameter, surgical margins were clear by at least 2 mm, the tumor did not contain an extensive intraductal component, the axilla was surgically staged with < or =3 nodes involved with cancer, and a postoperative mammogram was performed. Implants were positioned using a template guide delivering 50 Gy over 96 hr to the lumpectomy bed plus a 1-2-cm margin. Local control, cosmetic outcome, and complications were assessed. RESULTS: Patients ranged in age from 40 to 84 years (median, 65). The median tumor size was 10 mm (range, 1-25). Seventeen of 50 patients (34%) had well-differentiated tumors, 22 (44%) had moderately differentiated tumors, and in 11 (22%) the tumor was poorly differentiated. Forty-five patients (90%) were node-negative while five (10%) had 1-3 positive nodes. A total of 23 (46%) patients were placed on tamoxifen and 3 (6%) received adjuvant systemic chemotherapy. No patient was lost to follow-up. The median follow-up for surviving patients is 47 months (range, 37-59). No patient has experienced a local, regional, or distant failure. Three patients have died at 19, 33, and 39 months after treatment. All were without clinical evidence of recurrent disease and all deaths were unrelated to treatment. Good-to excellent cosmetic results have been observed in 49 of 50 patients (98%) (median cosmetic follow-up was 44 months with a range of 19-59). No patient has experienced significant sequelae related to their implant. CONCLUSIONS: Interim results with treatment of the tumor bed alone with an LDR interstitial implant appear promising. Long-term follow-up of these patients and additional studies will be necessary to establish the equivalence of this treatment approach compared to standard BCT. PMID- 9989419 TI - Preoperative angiography and embolization of large pelvic tumors. AB - BACKGROUND AND OBJECTIVES: Pelvic tumors are often large and difficult to excise with appropriate surgical margins due to their size, proximity to neurovascular structures, and major intraoperative bleeding. The purpose of this study is to evaluate the yield of preoperative angiography and embolization so as to facilitate achievement of good surgical results. METHODS: Eighteen patients who suffered from large pelvic tumors (average size, 10.7 cm x 8.3 cm x 3.7 cm), 15 primary and 3 metastatic, underwent surgery at our institution between 1990 and 1995, after preoperative angiography and embolization of the tumors. RESULTS: The efficacy of the procedure was high. In all but one patient, the grade of vascularity of the tumor was reduced by at least two levels (based on our new tumor vascularity scale. In most patients, appropriate surgical margins were achieved. The average perioperative blood loss was only 750 cc. Procedure associated complications were negligible. CONCLUSIONS: The results of this study call for the use of angiography and embolization in the management of patients with large pelvic tumors. PMID- 9989420 TI - Anaplastic transformation of papillary thyroid carcinoma in recurrent disease in regional lymph nodes: a histologic and immunohistochemical study. AB - BACKGROUND AND OBJECTIVES: Although the prognosis of papillary thyroid carcinoma is favorable in most cases, recurrent disease in the regional lymph nodes is not uncommon, and some patients die of recurrent disease that ultimately becomes unresectable. We studied the proliferative activity of cancer cells in recurrent foci in lymph nodes to see whether repeated recurrences might result in anaplastic transformation of papillary thyroid carcinoma. METHODS: Fourteen patients with papillary thyroid carcinoma who underwent reoperation for recurrent disease in the regional lymph nodes more than once were the subjects of the study. The histologic findings and proliferative activity of carcinoma foci at each recurrence were studied histologically and immunohistochemically. RESULTS: There were higher incidences of histologic features of poorly differentiated thyroid carcinoma in the metastatic foci in the lymph nodes as it recurred repeatedly, and the labeling indexes of proliferating cell nuclear antigen (PCNA) and nuclear antigen Ki-67 (MIB-1) increased. CONCLUSIONS: These observations suggest that papillary thyroid carcinoma may become more malignant, even undergo transformation to an anaplastic variety, as metastatic disease in the regional lymph nodes recurs repeatedly. PMID- 9989421 TI - Expectant management of stage A-1 (T1a) prostate cancer utilizing serum PSA levels: a preliminary report. AB - BACKGROUND AND OBJECTIVES: The natural history of stage A-1 (Tla) prostate cancer remains unpredictable. Although stage A-1 (Tla) was traditionally considered an indolent lesion, recent reports have documented the potential progression of stage A-1 (Tla) cancer. METHODS: Eight men aged 65 to 76 years at the time of diagnosis with stage A-1 (Tla) prostate cancer received no therapy. These men have been followed from 3 to 9.5 years (mean, 6.25 years). During this period, the patients have been followed with periodic rectal examinations and prostate specific antigen (PSA) levels. RESULTS: The PSA levels of five of the eight patients remain in the normal range and no patient has had a change in his rectal examination. In the three patients who had elevated PSA levels, there was no evidence of metastatic disease. No patient has died from prostate cancer; one patient died from cerebrovascular causes. CONCLUSIONS: Patients with stage A-1 (Tla) prostate cancer have an unpredictable natural history. PSA levels can be used to monitor disease progression and identify those patients where observation is no longer appropriate. PMID- 9989422 TI - Small cell carcinoma of the gallbladder. AB - BACKGROUND AND OBJECTIVES: Small cell carcinoma of the gallbladder is rare with only 36 cases reported in the literature. Early reports demonstrated an extremely poor prognosis for this histologic type. Five new cases are reported and the previous experience in the literature is reviewed to further clarify the clinical behavior of this malignancy. METHODS: A retrospective analysis is performed on 5 new cases. An extensive review of the literature is also performed. RESULTS: Twenty-eight pure small cell carcinomas and 8 combined small cell carcinomas with adenocarcinoma are reported in the literature. Conclusions from the literature review reveal that small cell carcinoma of the gallbladder affects an elderly patient population (median age 65 years), has a female preponderance (76%), is associated with cholelithiasis (72%), metastasizes to nodes (88%), liver (88%), lung (23%), and peritoneum (19%), and has a median survival of 4 months. Pure tumors had median survivals of 9 months and combined tumors had median survivals of 4.5 months. The 5 patients in the literature treated with surgery and chemotherapy had improved median survival of 13 months. The 5 newly reported cases had similar epidemiological characteristics to the literature data, however, these cases were managed aggressively with surgery and chemotherapy, demonstrating a median survival of 31 months. CONCLUSIONS: Although small cell carcinoma of the gallbladder is a distinct histologic and clinical entity, it has many clinical characteristics similar to adenocarcinoma of the gallbladder including comparable natural history and tendency for locoregional spread. Aggressive multimodality therapy, especially the combination of surgery and chemotherapy, may improve survival. PMID- 9989423 TI - Quality of life following surgery for vertebral metastases from breast cancer. AB - BACKGROUND AND OBJECTIVES: The quality of life of patients with vertebral metastases from breast cancer treated with surgery was evaluated. METHODS: Seven such patients underwent surgery for vertebral metastases following chemoendocrine treatment. They presented with pain and some with neurological compromise. RESULTS: Following posterior stabilization with a segmental instrument, pain was alleviated in all seven women, two showed improvements in neurological compromise, and performance status was improved in five. In no patient was there neurological deterioration secondary to surgical intervention. They were out of bed on the 4th postoperative day and discharged on the 14th day on average. CONCLUSIONS: The quality of life was improved for these surgically treated patients. We recommend surgical stabilization for selected patients with a vertebral metastasis from breast cancer. PMID- 9989424 TI - Oliguria, an unusual presentation of primary signet ring-cell adenocarcinoma of the urinary bladder: a case report and review of the literature. AB - Adenocarcinomas represent approximately 2% of primary bladder epithelial malignancies. Of these, the signet ring-cell variant is the rarest form. We report such a case, with the unusual presentation of oliguria, including radiologic and histopathologic findings. The current literature is reviewed. PMID- 9989425 TI - Neuropharmacology of brain-stimulation-evoked aggression. AB - Evidence is reviewed concerning the brain areas and neurotransmitters involved in aggressive behavior in the cat and rodent. In the cat, two distinct neural circuits involving the hypothalamus and PAG subserve two different kinds of aggression: defensive rage and predatory (quiet-biting) attack. The roles played by the neurotransmitters serotonin, GABA, glutamate, opioids, cholecystokinin, substance P, norepinephrine, dopamine, and acetylcholine in the modulation and expression of aggression are discussed. For the rat, a single area, largely coincident with the intermediate hypothalamic area, is crucial for the expression of attack; variations in the rat attack response in natural settings are due largely to environmental variables. Experimental evidence emphasizing the roles of serotonin and GABA in modulating hypothalamically evoked attack in the rat is discussed. It is concluded that significant progress has been made concerning our knowledge of the circuitry underlying the neural basis of aggression. Although new and important insights have been made concerning neurotransmitter regulation of aggressive behavior, wide gaps in our knowledge remain. PMID- 9989426 TI - On the similarity of odor and language perception. AB - The association between olfaction and language is discussed. The effects of odor on human behavior and cognitive processing are reviewed as are electrophysiological studies of odor/language interactions. Also reviewed are specific effects of odor administration on language-dependent tasks. The hypothesis is advanced that odor information processing shares some of the cortical resources used in processing language and that interference between these two types of stimuli occurs when they are simultaneously processed. The reason for this overlap in resources is thought to be due to the similarities in the spatio-temporal patterns produced in the neural coding of odors and language. PMID- 9989427 TI - Metabotropic glutamate receptor activation and blockade: their role in long-term potentiation, learning and neurotoxicity. AB - Metabotropic glutamate receptors represent a fairly recent addition to the family of glutamate receptors. These receptors have the distinguishing feature of being coupled to G-proteins rather than ion channels and they appear to have a variety of functional characteristics. These receptors play a vital role, for example, in the induction and maintenance of long-term potentiation, the most popular current model of the biological correlates of learning and memory. Blockade of metabotropic glutamate receptors prevents long-term potentiation induction and learning in a variety of tasks in different species. Chronic metabotropic glutamate receptor activation is also associated with neurodegeneration and selective neuronal loss when agonists of these receptors are injected in high concentrations directly into the brain. Metabotropic glutamate receptors also play a role in the normal development of the nervous system and these sites within the central nervous system offer possible routes for drug therapies; selective receptor antagonists, for example, may prove to have the very desirable feature of endowing neuroprotection during ischaemic episodes whilst allowing normal excitatory neurotransmission to occur. PMID- 9989428 TI - The biology of human parenting: insights from nonhuman primates. AB - Primate and human parenting have often been viewed as completely emancipated from neuroendocrine influences and primarily dependent on experience, social and cognitive processes. A review of recent findings of primate research on the neurobiological regulation of parental responsiveness, the causes of variability in parenting styles, and the determinants of infant abuse suggests that primate parenting is more sensitive to neuroendocrine mechanisms than previously thought. The findings of primate research can have important implications for human research and encourage the investigation of biological influences on human parenting. PMID- 9989429 TI - Glutamate and the UMAMI taste: sensory, metabolic, nutritional and behavioural considerations. A review of the literature published in the last 10 years. AB - Monosodium glutamate (MSG) is used increasingly often in processed foods and in home cooking in the Western world. This substance is responsible for a pleasurable taste sensation, the Umami taste. This review covers recent developments in sensory studies of glutamate effects, and traces the Umami taste from sensory receptors on the tongue to the brain. The metabolism of glutamic acid, as revealed from recent literature, is described. A specific section is devoted to safety issues. In addition, effects of glutamic salts on nutrition and ingestive behaviours are shown to be potent. Animal and human works are treated separately, with special attention to the specific methods used in both cases. Future areas of research include further investigation of sensory physiology, role of glutamate as an excitatory substance in the brain, acquisition of food likes and impact on long-term food selection, food intake, and body weight control. PMID- 9989430 TI - Unique salience of maternal breast odors for newborn infants. AB - Human infants are particularly responsive to olfactory cues emanating from their mother's nipple/areola region. Beginning within minutes after birth, maternal breast odors elicit preferential head orientation by neonates and help guide them to the nipple. Such odors also influence babies' general motor activity and arousal, which may contribute further to successful nipple localization and sucking. The role of maternal olfactory signals in the mediation of early breast feeding is functionally analogous to that of nipple-search pheromone as described in nonhuman mammals. To some extent, the chemical profile of breast secretions overlaps with that of amniotic fluid. Therefore, early postnatal attraction to odors associated with the nipple/areola may reflect prenatal exposure and familiarization. Although newborns are generally attracted to breast odors produced by lactating women, breast-fed infants rapidly learn their mother's characteristic olfactory signature while sucking at her breasts and can subsequently recognize her by that unique scent alone. Early odor-based recognition may be an important factor in the development of the infant-mother bond. PMID- 9989431 TI - Errors made by animals in memory paradigms are not always due to failure of memory. AB - It is commonly assumed that errors in animal memory paradigms such as delayed matching to sample, radial mazes, and food-cache recovery are due to failures in memory for information necessary to perform the task successfully. A body of research, reviewed here, suggests that this is not always the case: animals sometimes make errors despite apparently being able to remember the appropriate information. In this paper a case study of this phenomenon is described, along with a demonstration of a simple procedural modification that successfully reduced these non-memory errors, thereby producing a better measure of memory. PMID- 9989432 TI - The effects of stochastic galvanic vestibular stimulation on human postural sway. AB - Galvanic vestibular stimulation serves to modulate the continuous firing level of the peripheral vestibular afferents. It has been shown that the application of sinusoidally varying, bipolar galvanic currents to the vestibular system can lead to sinusoidally varying postural sway. Our objective was to test the hypothesis that stochastic galvanic vestibular stimulation can lead to coherent stochastic postural sway. Bipolar binaural stochastic galvanic vestibular stimulation was applied to nine healthy young subjects. Three different stochastic vestibular stimulation signals, each with a different frequency content (0-1 Hz, 1-2 Hz, and 0-2 Hz), were used. The stimulation level (range 0.4-1.5 mA, peak to peak) was determined on an individual basis. Twenty 60-s trials were conducted on each subject - 15 stimulation trials (5 trials with each stimulation signal) and 5 control (no stimulation) trials. During the trials, subjects stood in a relaxed, upright position with their head facing forward. Postural sway was evaluated by using a force platform to measure the displacements of the center of pressure (COP) under each subject's feet. Cross-spectral measures were used to quantify the relationship between the applied stimulus and the resulting COP time series. We found significant coherency between the stochastic vestibular stimulation signal and the resulting mediolateral COP time series in the majority of trials in 8 of the 9 subjects tested. The coherency results for each stimulation signal were reproducible from trial to trial, and the highest degree of coherency was found for the 1- to 2-Hz stochastic vestibular stimulation signal. In general, for the nine subjects tested, we did not find consistent significant coherency between the stochastic vestibular stimulation signals and the anteroposterior COP time series. This work demonstrates that, in subjects who are facing forward, bipolar binaural stochastic galvanic stimulation of the vestibular system leads to coherent stochastic mediolateral postural sway, but it does not lead to coherent stochastic anteroposterior postural sway. Our finding that the coherency was highest for the 1- to 2-Hz stochastic vestibular stimulation signal may be due to the intrinsic dynamics of the quasi-static postural control system. In particular, it may result from the effects of the vestibular stimulus simply being superimposed upon the quiet-standing COP displacements. By utilizing stochastic stimulation signals, we ensured that the subjects could not predict a change in the vestibular stimulus. Thus, our findings indicate that subjects can act as "responders" to galvanic vestibular stimulation. PMID- 9989433 TI - A fronto-parietal system for computing the egocentric spatial frame of reference in humans. AB - Spatial orientation is based on coordinates referring to the subject's body. A fundamental principle is the mid-sagittal plane, which divides the body and space into the left and right sides. Its neural bases were investigated by functional magnetic resonance imaging (fMRI). Seven normal subjects pressed a button when a vertical bar, moving horizontally, crossed the subjective mid-sagittal plane. In the control condition, the subjects' task was to press a button when the direction of the bar movement changed, at the end of each leftward or rightward movement. The task involving the computation of the mid-sagittal plane yielded increased signal in posterior parietal and lateral frontal premotor regions, with a more extensive activation in the right cerebral hemisphere. This direct evidence in normal human subjects that a bilateral, mainly right hemisphere based, cortical network is active during the computation of the egocentric reference is consistent with neuropsychological studies in patients with unilateral cerebral lesions. Damage to the right hemisphere, more frequently to the posterior-inferior parietal region, may bring about a neglect syndrome of the contralesional, left side of space, including a major rightward displacement of the subjective mid-sagittal plane. The existence of a posterior parietal-lateral premotor frontal network concerned with egocentric spatial reference frames is also in line with neurophysiological studies in the monkey. PMID- 9989434 TI - Stronger occipital cortical activation to lower than upper visual field stimuli. Neuromagnetic recordings. AB - We recorded whole-scalp magnetoencephalographic (MEG) responses to black-and white checkerboards to study whether the human cortical responses are quantitatively similar to stimulation of the lower and upper visual field at small, 0-6 degrees, eccentricities. All stimuli evoked strong occipital responses peaking at 50-100 ms (mean 75 ms). The activation was modeled with a single equivalent current dipole in the contralateral occipital cortex, close to the calcarine fissure, agreeing with an activation of the V1/V2 cortex. The dipole was, on average, twice as strong to lower than to upper field stimuli. Responses to hemifield stimuli that extended to both lower and upper fields resembled the responses to lower field stimuli in source current direction and strength. These results agree with psychophysical data, which indicate lower visual field advantage in complex visual processing. Parieto-occipital responses in the putative V6 complex were similar to lower and upper field stimuli. PMID- 9989435 TI - Contribution of NMDA and non-NMDA receptors to synaptic transmission from the brachium of the inferior colliculus to the medial subdivision of the medial geniculate nucleus in the rabbit. AB - Previous work from this laboratory has demonstrated that monosynaptic inputs from the brachium of the inferior colliculus (BIC) to the medial subdivision of the medial geniculate nucleus (mMG) strengthen as a result of associative conditioning with an acoustic conditioned stimulus (i.e., fear conditioning). One model that has been proposed to underlie certain types of neuronal plasticity involves the recruitment of N-methyl-D-aspartic acid (NMDA)-type glutamate receptors. The purpose of the present study was to examine the relative contributions of glutamatergic NMDA and non-NMDA receptors to synaptic transmission within this pathway. Individual contributions of the specific receptor types were assessed through the use of 2-amino-5-phosphonovaleric acid (AP5), a selective NMDA receptor antagonist, and 6-cyano-5-nitroquinoxaline-2,3 dione (CNQX), a non-NMDA receptor antagonist. Bipolar stimulating electrodes were stereotaxically implanted in BIC and recording electrodes (attached to dual 32 gauge cannulae for delivery of drug) were positioned in mMG of New Zealand albino rabbits. Single pulses (150 micros, 100-350 microA) delivered to BIC resulted in short-latency (<4 ms) responses in mMG. BIC-evoked single-unit activity was recorded from mMG before, during, and at several intervals after injection of AP5, CNQX, and/or artificial cerebrospinal fluid (ACSF). Injection of either AP5 or CNQX, but not ACSF, significantly attenuated the short-latency BIC-evoked responses in the vast majority of cells tested. These findings suggest that the monosynaptic pathway from BIC to mMG is glutamatergic and that this pathway frequently employs NMDA-type receptors during electrically stimulated synaptic transmission. Due to the NMDA receptors' proposed role in plasticity (e.g., long term potentiation), these results may have implications for understanding the mechanisms of synaptic plasticity observed at this synapse during associative learning. PMID- 9989436 TI - Spinal cord implantation of avulsed ventral roots in primates; correlation between restored motor function and morphology. AB - Functional restitution following spinal cord implantation of avulsed ventral roots was assessed electromyographically and correlated with the morphology of the regenerated neural structures in primates. The C5-C8 ventral roots were avulsed from the spinal cord in seven Macaca fascicularis monkeys. In three animals the roots were immediately reimplanted into the ventrolateral part of the spinal cord. In two monkeys the avulsed roots were reimplanted with a delay of 2 months and in two control animals the roots were not reimplanted. There was substantial recovery of function after both immediate and delayed spinal cord implantation of the avulsed ventral roots. The population of neurons that had regenerated was larger than on the control side, indicating a rescue of cells after an immediate root implantation. Different functional types of neurons had been attracted to regrow axons to the implanted root as judged by their position in the ventral horn. Thus, neurons normally supplying antagonistic muscles, such as the triceps muscle, participated in the innervation of the biceps muscle. Functionally this deficient directional specificity was correlated to both spasticity and co-contractions among agonistic and antagonistic muscles. Occasional electromyographic signs of function occurred also in control animals where the avulsed roots had not been implanted. This recovery was found to depend on regrowth from the site of avulsion, within the pia mater among the leptomeningeal cells and to the avulsed roots. The acceptable functional dexterity regained due to corrective surgery is discussed in terms of neurotrophism and plasticity. PMID- 9989437 TI - Time course of simultaneous masking in the starling's auditory forebrain. AB - Simultaneous masking of pure tones was studied in the primary auditory forebrain of a songbird species, the European starling (Sturnus vulgaris). The responses of 32 multi-unit clusters in the input layer of the auditory neostriatum (field L2a) were recorded via radiotelemetry from freely moving birds. The probe was a 10-ms tone burst at the units' characteristic-frequency (CF) presented 20 dB above the threshold. The masker was an 80-ms tone burst presented either at the units' CF (excitatory masker) or at a frequency located in inhibitory side-bands (inhibitory masker) of the units' tuning curves. The probe was presented either 3 ms or 63 ms after masker onset. Probes presented at a 3-ms delay were influenced at significantly lower levels of an excitatory masker than probes presented at a 63-ms delay. The mean difference in masker level at the detection thresholds for both probe delays was 8 dB. No difference in masker level was observed for inhibitory-frequency maskers. The observed neural masking effects may be explained by at least four mechanisms: (1) swamping of the probe response by the response to the masker, (2) a reduction of the probe response during neural adaptation of the response to the masker, (3) a reduction of the probe response during side-band inhibition in the central nervous system, and (4) suppression originating in the cochlea. PMID- 9989438 TI - Task-dependent modulation of inhibitory actions within the primary motor cortex. AB - In 11 healthy subjects motor-evoked potentials (MEPs) and silent periods (SPs) were measured in the right first dorsal interosseus (FDI) and abductor pollicis brevis muscles (APB): (1) when transcranial magnetic cortex stimulation (TMS) was applied at tonic isometric contraction of 20% of maximum force, (2) when TMS was applied during tactile exploration of a small object in the hand, (3) when TMS was applied during visually guided goal-directed isometric ramp and hold finger flexion movements, and (4) when at tonic isometric contraction peripheral electrical stimulation (PES) of the median nerve was delivered at various intervals between PES and TMS. Of the natural motor tasks, duration of SPs of small hand muscles was longest during tactile exploration (APB 205+/-42 ms; FDI 213+/-47 ms). SP duration at tonic isometric contraction amounted to 172+/-35 ms in APB and 178+/-31 ms in FDI, respectively. SP duration in FDI was shortest when elicited during visually guided isometric finger movements (159+/-15 ms). At tonic isometric contraction, SP was shortened when PES was applied at latencies 30 to +70 ms in conjunction with TMS. The latter effect was most pronounced when PES was applied 20 ms before TMS. PES-induced effects increased with increasing stimulation strength up to a saturation level which appeared at the transition to painful stimulation strengths. Both isolated stimulation of muscle afferents and of low-threshold cutaneous afferents shortened SP duration. However, PES of the contralateral median nerve had no effect on SPs. Amplitudes of MEPs did not change significantly in any condition. Inhibitory control of motor output circuitries seems to be distinctly modulated by peripheral somatosensory and visual afferent information. We conclude that somatosensory information has privileged access to inhibitory interneuronal circuits within the primary motor cortex. PMID- 9989439 TI - Standing on a continuously moving platform: is body inertia counteracted or exploited? AB - We describe the characteristics of displacement of the head and hip in normal young subjects standing on a moving platform undergoing continuous sinusoidal horizontal translation in the antero-posterior direction, at frequencies ranging from 0.1-1 Hz. The head, hip and malleolus were marked by light-emitting diodes (LEDs), and the displacement of each LED was quantified by (1) the measure of the shift during each cycle of translation, (2) the standard deviation (SD) of the path travelled during the whole trial, (3) the power spectrum (PS) of the signal and (4) the cross-correlation (CC) between pairs of LED signals. At each frequency of translation, with eyes open (EO), the displacement of head was smaller than that of hip, and the displacement of hip was smaller than that of malleolus. With eyes closed (EC), this order was reversed. The peak value of the CC functions of the pairs malleolus/head, malleolus/hip and hip/head decreased by passing from low to high frequency of translation, under both visual conditions, and decreased more for the pair malleolus/head than malleolus/hip. The lags between body segment displacements ranged between 30 ms and 150 ms, on average, the former segment of each pair preceding the latter. The fast Fourier transformation of hip and head displacement showed a power spectrum peak at the frequency imposed by the platform translation. The peak was larger with EC than EO. With EC, another peak appeared at 0.2 Hz, possibly corresponding to the respiratory frequency. We conclude that, when vision was allowed, subjects behaved as a non-rigid, noninverted pendulum, and stabilised head in space. When vision was denied, head oscillated more than the platform, especially at low translation frequencies. Therefore, the strategy of balance control shifted from a pendulum to an inverted-pendulum behaviour, passing from active head-and-trunk control to maximal body compliance to the perturbation. PMID- 9989440 TI - Antagonist motor responses correlate with kinesthetic illusions induced by tendon vibration. AB - In humans, vibration applied to muscle tendons evokes illusory sensations of movement that are usually associated with an excitatory tonic response in muscles antagonistic to those vibrated (antagonist vibratory response or AVR). The aim of the present study was to investigate the neurophysiological mechanisms underlying such a motor response. For that purpose, we analyzed the relationships between the parameters of the tendon vibration (anatomical site and frequency) and those of the illusory movement perceived (direction and velocity), as well as the temporal, spatial, and quantitative characteristics of the corresponding AVRs (i.e., surface EMG, motor unit firing rates and activation latencies). Analogies were supposed between the characteristics of AVRs and voluntary contractions. The parameters of the AVR were thus compared with those of a voluntary contraction with similar temporal and mechanical characteristics, involving the same muscle groups as those activated by vibration. Wrist flexor muscles were vibrated either separately or simultaneously with wrist extensor muscles at frequencies between 30 and 80 Hz. The illusory movement sensations were quantified through contralateral hand-tracking movements. Electromyographic activity from the extensor carpi radialis muscles was recorded with surface and intramuscular microelectrodes. The results showed that vibration of the wrist flexor muscle group induced both a kinesthetic illusion of wrist extension and a motor response in the extensor carpi radialis muscles. Combined vibration of the two antagonistic muscle groups at the same frequency evoked neither kinesthetic illusion nor motor activity. In addition, vibrating the same two antagonistic muscle groups at different frequencies induced both a kinesthetic illusion and a motor response in the muscle vibrated at the lowest frequency. The surface EMG amplitude of the extensor carpi radialis as well as the motor unit activation latency and discharge frequency were clearly correlated to the parameters of the illusory movement evoked by the vibration. Indeed, the faster the illusory sensation of movement, the greater the surface EMG in these muscles during the AVRs and the sooner and the more intense the activation of the motor units of the wrist extensor muscles. Moreover, comparison of the AVR with voluntary contraction showed that all parameters were highly similar. Mainly slow motor units were recruited during the AVR and during its voluntary reproduction. That the AVR is observed only when a kinesthetic illusion is evoked, together with the similarities between voluntary contractions and AVRs, suggests that this vibration-induced motor response may result from a perceptual-to-motor transformation of proprioceptive information, rather than from spinal reflex mechanisms. PMID- 9989441 TI - Effects of short-term adaptation of saccadic gaze amplitude on hand-pointing movements. AB - We investigated whether and how adaptive changes in saccadic amplitudes (short term saccadic adaptation) modify hand movements when subjects are involved in a pointing task to visual targets without vision of the hand. An experiment consisted of the pre-adaptation test of hand pointing (placing the finger tip on a LED position), a period of adaptation, and a post-adaptation test of hand pointing. In a basic task (transfer paradigm A), the pre- and post-adaptation trials were performed without accompanying eye and head movements: in the double step gaze adaptation task, subjects had to fixate a single, suddenly displaced visual target by moving eyes and head in a natural way. Two experimental sessions were run with the visual target jumping during the saccades, either backwards (from 30 to 20 degrees, gaze saccade shortening) or onwards (30 to 40 degrees, gaze saccade lengthening). Following gaze-shortening adaptation (level of adaptation 79+/-10%, mean and s.d.), we found a statistically significant shift (t-test, error level P<0.05) in the final hand-movement points, possibly due to adaptation transfer, representing 15.2% of the respective gaze adaptation. After gaze-lengthening adaptation (level of adaptation 92+/-17%). a non-significant shift occurred in the opposite direction to that expected from adaptation transfer. The applied computations were also performed on some data of an earlier transfer paradigm (B, three target displacements at a time) with gain shortening. They revealed a significant transfer relative to the amount of adaptation of 18.5< or = 17.5% (P<0.05). In the coupling paradigm (C), we studied the influence of gaze saccade adaptation of hand-pointing movements with concomitant orienting gaze shifts. The adaptation levels achieved were 59+/-20% (shortening) and 61+/ 27% (lengthening). Shifts in the final fingertip positions were congruent with internal coupling between gaze and hand, representing 53% of the respective gaze amplitude changes in the shortening session and 6% in the lengthening session. With an adaptation transfer of less than 20% (paradigm A and B), we concluded that saccadic adaptation does not "automatically" produce a functionally meaningful change in the skeleto-motor system controlling hand-pointing movements. In tasks with concomitant gaze saccades (coupling paradigm C), the modification of hand pointing by the adapted gaze comes out more clearly, but only in the shortening session. PMID- 9989442 TI - Loading during the stance phase of walking in humans increases the extensor EMG amplitude but does not change the duration of the step cycle. AB - Prior work from mammals suggests that load experienced by extensor muscles of the hindlimbs (i.e. Duysens and Pearson 1980; Pearson and Collins 1993; Fouad and Pearson 1997) or cutaneous afferents from the plantar surface of the foot (Duysens and Pearson 1976; Guertin et al. 1995) enhances activity in extensor muscles during the stance phase, and delays the onset of flexor activity associated with the swing phase. The presumed functional significance of this phenomenon is that extensor activity of the supporting limb during walking can: (a) reinforce the supporting function in proportion to the load experienced, and (b) prolong the stance phase until unloading of the limb has occurred. Whether a similar functional role exists for load-sensitive afferents during walking in the human is unknown. In this study, the effect of adding or removing a substantial load (30% of body weight) at the centre of mass was studied in healthy adult human subjects. Loads were applied near the centre of mass to avoid the need for postural adjustments which might confound the interpretation of the results. Subjects walked on a treadmill with either: (a) a sustained increase or decrease in load, or (b) a sudden unexpected increase or decrease in load. In general, subjects responded to the changes in load by changing the amplitude of the extensor electromyographic (EMG) bursts. For example, with sudden unexpected additions in load, the average increase in amplitude was 40% for the soleus across the stance phase, and 134% for the quadriceps during the early part of the stance phase. Extensor EMGs increased with both sustained and sudden increases in load. Extensor EMG durations also increased (average increase in duration of 4% for soleus with sudden loading, and 7% for sustained loading). Cycle duration hardly changed (average increase of 0.5% with both sudden and sustained loading). These results differ from those of infants subjected to a similar perturbation during supported walking. A large change in timing (i.e. an increase in the duration of the stance phase by 30% and the step cycle by 28%) was seen in the infants, with no change in the amplitude of the EMG burst (Yang et al. 1998). These results suggest that the central nervous system can control the timing and amplitude of extensor EMG activity in response to loading independently. Maturation of the two components most likely occurs independently. In the adult, independent control of the two components may provide greater flexibility of the response. PMID- 9989443 TI - Neonatal control of nutritive sucking pressure: evidence for an intrinsic tau guide. AB - Human newborns appear to regulate sucking pressure when bottle feeding by employing, with similar precision, the same principle of control evidenced by adults in skilled behavior, such as reaching (Lee et al., 1998a). In particular, the present study of 12 full-term newborn infants indicated that the intraoral sucking pressures followed an internal dynamic prototype - an intrinsic tau guide. The intrinsic tau-guide, a recent hypothesis of general tau theory is a time-varying quantity, tau(g), assumed to be generated within the nervous system. It corresponds to some quantity (e.g., electrical charge), changing with a constant second-order temporal derivative from a rest level to a goal level, in the sense that tau(g) equals tau of the gap between the quantity and its goal level at each time t. (tau of a gap is the time-to-closure of the gap at the current closure-rate.) According to the hypothesis, the infant senses tau(p), the tau of the gap between the current intraoral pressure and its goal level, and regulates intraoral pressure so that tau(p) and tau(g), remain coupled in a constant ratio, k; i.e., tau(p)=k tau(g). With k in the range 0-1, the tau coupling would result in a bell-shaped rate of change pressure profile, as was, in fact, found. More specifically, the high mean r2 values obtained when regressing tau(p) on tau(g), for both the increasing and decreasing suction periods of the infants' suck, supported a strong tau-coupling between tau(p) and tau(g). The mean k values were significantly higher in the increasing suction period, indicating that the ending of the movement was more forceful, a finding which makes sense given the different functions of the two periods of the suck. PMID- 9989444 TI - Receptive-field properties of adult cat's retinal ganglion cells with regenerated axons. AB - Receptive-field properties of retinal ganglion cells (RGCs) that had regenerated their axons were studied by recording single-unit activity from strands teased from peripheral nerve (PN) grafts apposed to the cut optic nerve in adult cats. Of the 286 visually responsive units recorded from PN grafts in 20 cats, 49.7% were classified, according to their receptive-field properties, as Y-cells, 39.5% as X-cells, 6.6% as W-cells, and 4.2% were unclassified. The predominant representation of Y-cells is consistent with a corresponding morphological study (Watanabe et al. 1993a), which identified alpha-cells as the RGC type with the largest proportion of regenerating axons. Among the X-cells, we only found ON center types, whereas both ON-center and OFF-center Y-cells were found. As in intact retinas, the receptive-field center sizes of Y-cells and W-cells were larger than those of X-cells at corresponding displacements from the area centralis. Within the 10 degrees surrounding the area centralis, the receptive fields of X-cells with regenerated axons were larger than those in intact retinas, suggesting that some rearrangement of retinal circuitry occurred as a consequence of degeneration and regeneration. Receptive-field center responses of Y-, X-, and W-type units with regenerated axons were similar to those found in intact retinas, but the level of spontaneous activity of Y- and X-type units was, in general, less than that of intact RGCs. Receptive-field surrounds were weak or not detected in more than half of the visually responsive RGCs with regenerated axons. PMID- 9989445 TI - The simple reaction time to changes in direction of visual motion. AB - Recently Dzhafarov et al. presented a model explaining data on simple reaction time (RT) to unidimensional velocity changes. The authors suggested that having a motion with an initial velocity V0, the velocity change detection system is reinitialized by means of a "subtractive normalization" process. Therefore, any abrupt change from V0 to V1 is detected as if it were the onset of motion with a speed equal to /V1-V0/. They derived that the RT is a function of /V1-V0/(-2/3). We tested this model for the case of two-dimensional velocity changes. Our subjects observed a random dot pattern that moved horizontally, then changed the direction of motion by an angle alpha in the range between 6 degrees and 180 degrees without changing the speed V. Speeds of 4 and 12 deg/s were used. The subjects reacted as quickly as possible to the direction change. The RTs asymptotically decreased with increasing alpha; with 12 deg/s speed the RTs were shorter than those obtained with 4 deg/s. It was shown that the data can be well described as a function of /V1-V0/(-2/3)=(2Vsin(alpha/2))(-2/3). An extension of the "subtractive normalization" hypothesis for the case of two-dimensional velocity changes is proposed. It is based on the assumption that the velocity vector V1 after the change is decomposed into two orthogonal components. Alternative explanations based on the use of position or orientation cues are shown to contradict the data. PMID- 9989446 TI - Supratentorial pilocytic astrocytomas, astrocytomas, anaplastic astrocytomas and glioblastomas are characterized by a differential expression of S100 proteins. AB - The levels of expression of the S100A1, S100A2, S100A3, S100A4, S100A5, S100A6 and S100B proteins were immunohistochemically assayed and quantitatively determined in a series of 95 astrocytic tumors including 26 World Health Organization (WHO) grade I (pilocytic astrocytomas), 23 WHO grade II (astrocytomas), 25 WHO grade III (anaplastic astrocytomas) and 21 WHO grade IV (glioblastomas) cases. The level of the immunohistochemical expression of the S100 proteins was quantitatively determined in the solid tumor tissue (tumor mass). In addition twenty blood vessel walls and their corresponding perivascular tumor astrocytes were also immunohistochemically assayed for 10 cases chosen at random from each of the four histopathological groups. The data showed modifications in the level of S100A3 protein expression; these modifications clearly identified the pilocytic astrocytomas from WHO grade II-IV astrocytic tumors as a distinct biological group. Modifications in the level of S100A6 protein expression enabled a clear distinction to be made between low (WHO grade I and II) and high (WHO grade III and IV) grade astrocytic tumors. Very significant modifications occurred in the level of S100A1 protein expression (and, to a lesser extent, in their of the S100A4 and S100B proteins) in relation to the increasing levels of malignancy. While the S100A5 protein was significantly expressed in all the astrocytic tumors (but without any significant modifications in the levels of malignancy), the S100A2 protein was never expressed in these tumors. These data thus indicate that several S100 proteins play major biological roles in human astrocytic tumors. PMID- 9989447 TI - CNS cell populations are protected from virus-induced pathology by distinct arms of the immune system. AB - The basis for the distinct patterns of brain pathology in individuals experiencing virus-induced encephalitis may be related to either the tropism of the virus or the host's response to virus infection of the central nervous system (CNS). In these studies we used Theiler's murine encephalomyelitis virus (TMEV) and a series of mice deficient in various immune system components (alpha/beta T cells, antibody, Class I MHC, and Class II MHC) to examine the hypothesis that discrete populations of CNS cells are protected differentially from virus infection by distinct arms of the immune response. Here we demonstrate that the Class I-mediated immune response provided more protection from areas of the brain (brainstem, corpus callosum and cerebellum) with abundant white matter as there was significantly more disease in these areas in beta2m -/- (Class I-deficient) mice as compared to A beta(0) (Class II-deficient) mice. In contrast, the striatum, with an abundance of neurons, was protected from virus-induced pathology primarily by antibody. In addition, we determined that antibody and alpha/beta T cells provided protection from severe deficits and death during the acute phase of the disease. The data presented here support the hypothesis that distinct immune system components function to protect discrete areas of the CNS from virus-induced pathology. PMID- 9989448 TI - Identification in human brain tumors of DNA sequences specific for SV40 large T antigen. AB - Simian virus 40 (SV40) sequences have recently been identified in a variety of human neoplasms, including mesothelioma, osteosarcoma, and brain tumors, but significant discrepancies exist regarding the frequency at which this occurs. The SV40 genome is 70% homologous to JC and BK, two related polyomaviruses that are highly prevalent in humans and which may cause in immune-compromised patients progressive multifocal leukoencephalopathy (PML) and cystitis, respectively. We have established a specific and sensitive method to identify SV40 sequence in DNA extracted from histological sections, using PCR followed by Southern hybridization to probes specific to the large T region. We found SV40 large T antigen sequences in all brain tumor types investigated. High frequencies were found in low-grade astrocytomas, anaplastic astrocytomas and secondary glioblastomas derived thereof (13/22, 59%) while somewhat lower frequencies were found in gemistocytic astrocytomas (9/28, 32%) and oligodendrogliomas (3/12, 25%). Primary glioblastomas, giant cell glioblastomas, and gliosarcomas, which clinically develop de novo, contained SV40 sequences in 11-25% of cases. Presence of viral DNA was also observed in pediatric brain tumors, including ependymomas (9/16, 56%), choroid plexus papillomas (6/16, 38%), and medulloblastomas (5/17, 29%). In 8 tumor biopsies with SV40 sequences, the adjacent normal brain tissue was also analyzed but was devoid of viral DNA in all but one case. BK and JC virus sequences were rarely detected, the overall frequencies being 3% and 2%, respectively. It remains to be shown whether the presence of SV40 contributes significantly to malignant transformation or whether certain human neoplasms provide a microenvironment that favors viral replication in humans with latent SV40 infection. PMID- 9989449 TI - Is SV40 a tumorigenic human pathogen? PMID- 9989450 TI - Co-localization of TSC1 and TSC2 gene products in tubers of patients with tuberous sclerosis. AB - Two genes, mutations in which result in the phenotype of tuberous sclerosis (TSC), have recently been cloned. TSC2 on chromosome 16p13.3 encodes the protein tuberin, which appears to have growth regulating properties. TSC1 on chromosome 9q34 encodes hamartin which, as yet, has no specified cellular functions. Polyclonal antibodies were raised to synthetic peptides representing portions of tuberin and hamartin and used in immunoblots and immunohistochemical studies to localize the proteins in surgically resected neocortical tubers from four TSC patients. On Western blots of autopsy brain specimens, K-562 cell, and NT2 lysates, each antibody labelled a single band at the expected molecular weight. In immunohistochemical protocols on paraffin embedded tissue, antibodies to both tuberin and hamartin prominently labelled atypical and dysmorphic neuroglial cells that are a defining feature of TSC tubers. Some abnormal cells within cortical tuber sections were labelled with both tuberin and hamartin antisera. Our results suggest that tuberin and hamartin are both robustly expressed in similar populations of neuroglial cells of TSC tubers, even in the presence of TSC1 or TSC2 germline mutations. The roles of these gene products in normal and abnormal cortical development, tuber pathogenesis and the generation of seizures remain to be defined. PMID- 9989452 TI - Oxidative stress in bacterial meningitis. AB - Fifty years after the advent of antibiotics for clinical use, the rates of morbidity and mortality associated with bacterial meningitis remain high. The unfavourable clinical outcome is often due to intracranial complications including cerebrovascular insults, raised intracranial pressure, hydrocephalus, and brain edema. Reactive oxygen species (ROS) are known effector molecules in the antimicrobial armature of polymorphonuclear and mononuclear phagocytes. However, over the last decade, there has been a substantial body of work implicating a central role of ROS in the development of intracranial complications and brain damage in bacterial meningitis. Recently, it also became evident that reactive nitrogen species (RNS), especially nitric oxide, are important mediators of meningitis-associated pathophysiological changes, at least during the early phase of the disease. There is now substantial evidence that much of the oxidative injury associated by simultaneous production of superoxide and nitric oxide is mediated by the strong oxidant peroxynitrite. ROS and peroxynitrite can be cytotoxic via a number of independent mechanisms. Their cytotoxic effects include initiation of lipid peroxidation and induction of DNA single strand breakage. Damaged DNA activates poly(ADP-ribose) polymerase (PARP). Recent experimental data propose a role of lipid peroxidation and PARP activation in the development of meningitis-associated intracranial complications and brain injury. Agents which interfere with the production of ROS and peroxynitrite, as well as with PARP activation and lipid peroxidation may represent novel, therapeutic strategies to limit meningitis-associated brain damage, and, thus, to improve the outcome of this serious disease. PMID- 9989453 TI - Demyelination: the role of reactive oxygen and nitrogen species. AB - This review summarises the role that reactive oxygen and nitrogen species play in demyelination, such as that occurring in the inflammatory demyelinating disorders multiple sclerosis and Guillain-Barre syndrome. The concentrations of reactive oxygen and nitrogen species (e.g. superoxide, nitric oxide and peroxynitrite) can increase dramatically under conditions such as inflammation, and this can overwhelm the inherent antioxidant defences within lesions. Such oxidative and/or nitrative stress can damage the lipids, proteins and nucleic acids of cells and mitochondria, potentially causing cell death. Oligodendrocytes are more sensitive to oxidative and nitrative stress in vitro than are astrocytes and microglia, seemingly due to a diminished capacity for antioxidant defence, and the presence of raised risk factors, including a high iron content. Oxidative and nitrative stress might therefore result in vivo in selective oligodendrocyte death, and thereby demyelination. The reactive species may also damage the myelin sheath, promoting its attack by macrophages. Damage can occur directly by lipid peroxidation, and indirectly by the activation of proteases and phospholipase A2. Evidence for the existence of oxidative and nitrative stress within inflammatory demyelinating lesions includes the presence of both lipid and protein peroxides, and nitrotyrosine (a marker for peroxynitrite formation). The neurological deficit resulting from experimental autoimmune demyelinating disease has generally been reduced by trial therapies intended to diminish the concentration of reactive oxygen species. However, therapies aimed at diminishing reactive nitrogen species have had a more variable outcome, sometimes exacerbating disease. PMID- 9989454 TI - Oxidative metabolism, apoptosis and perinatal brain injury. AB - Perinatal hypoxic-ischaemic injury (HII) is a significant cause of neurodevelopmental impairment and disability. Studies employing 31P magnetic resonance spectroscopy to measure phosphorus metabolites in situ in the brains of newborn infants and animals have demonstrated that transient hypoxia-ischaemia leads to a delayed disruption in cerebral energy metabolism, the magnitude of which correlates with the subsequent neurodevelopmental impairment. Prominent among the biochemical features of HII is the loss of cellular ATP, resulting in increased intracellular Na+ and Ca2+, and decreased intracellular K+. These ionic imbalances, together with a breakdown in cellular defence systems following HII, can contribute to oxidative stress with a net increase in reactive oxygen species. Subsequent damage to lipids, proteins, and DNA and inactivation of key cellular enzymes leads ultimately to cell death. Although the precise mechanisms of neuronal loss are unclear, it is now clear both apoptosis and necrosis are the significant components of cell death following HII. A number of different factors influence whether a cell will undergo apoptosis or necrosis, including the stage of development, cell type, severity of mitochondrial injury and the availability of ATP for apoptotic execution. This review will focus on some pathological mechanisms of cell death in which there is a disruption to oxidative metabolism. The first sections will discuss the process of damage to oxidative metabolism, covering the data collected both from human infants and from animal models. Following sections will deal with the molecular mechanisms that may underlie cerebral energy failure and cell death in this form of brain injury, with a particular emphasis on the role of apoptosis and mitochondria. PMID- 9989455 TI - Oxidative stress in brain ischemia. AB - Brain ischemia initiates a complex cascade of metabolic events, several of which involve the generation of nitrogen and oxygen free radicals. These free radicals and related reactive chemical species mediate much of damage that occurs after transient brain ischemia, and in the penumbral region of infarcts caused by permanent ischemia. Nitric oxide, a water- and lipid-soluble free radical, is generated by the action of nitric oxide synthases. Ischemia causes a surge in nitric oxide synthase 1 (NOS 1) activity in neurons and, possibly, glia, increased NOS 3 activity in vascular endothelium, and later an increase in NOS 2 activity in a range of cells including infiltrating neutrophils and macrophages, activated microglia and astrocytes. The effects of ischemia on the activity of NOS 1, a Ca2+-dependent enzyme, are thought to be secondary to reversal of glutamate reuptake at synapses, activation of NMDA receptors, and resulting elevation of intracellular Ca2+. The up-regulation of NOS 2 activity is mediated by transcriptional inducers. In the context of brain ischemia, the activity of NOS 1 and NOS 2 is broadly deleterious, and their inhibition or inactivation is neuroprotective. However, the production of nitric oxide in blood vessels by NOS 3, which, like NOS 1, is Ca2+-dependent, causes vasodilatation and improves blood flow in the penumbral region of brain infarcts. In addition to causing the synthesis of nitric oxide, brain ischemia leads to the generation of superoxide, through the action of nitric oxide synthases, xanthine oxidase, leakage from the mitochondrial electron transport chain, and other mechanisms. Nitric oxide and superoxide are themselves highly reactive but can also combine to form a highly toxic anion, peroxynitrite. The toxicity of the free radicals and peroxynitrite results from their modification of macromolecules, especially DNA, and from the resulting induction of apoptotic and necrotic pathways. The mode of cell death that prevails probably depends on the severity and precise nature of the ischemic injury. Recent studies have emphasized the role of peroxynitrite in causing single-strand breaks in DNA, which activate the DNA repair protein poly(ADP ribose) polymerase (PARP). This catalyzes the cleavage and thereby the consumption of NAD+, the source of energy for many vital cellular processes. Over activation of PARP, with resulting depletion of NAD+, has been shown to make a major contribution to brain damage after transient focal ischemia in experimental animals. Neuronal accumulation of poly(ADP-ribose), the end-product of PARP activity has been demonstrated after brain ischemia in man. Several therapeutic strategies have been used to try to prevent oxidative damage and its consequences after brain ischemia in man. Although some of the drugs used in early studies were ineffective or had unacceptable side effects, other trials with antioxidant drugs have proven highly encouraging. The findings in recent animal studies are likely to lead to a range of further pharmacological strategies to limit brain injury in stroke patients. PMID- 9989456 TI - Oxidative alterations in Alzheimer's disease. AB - There is increasing evidence that free radical damage to brain lipids, carbohydrates, proteins, and DNA is involved in neuron death in neurodegenerative disorders. The largest number of studies have been performed in Alzheimer's disease (AD) where there is considerable support for the oxidative stress hypothesis in the pathogenesis of neuron degeneration. In autopsied brain there is an increase in lipid peroxidation, a decline in polyunsaturated fatty acids (PUFA) and an increase in 4-hydroxynonenal (HNE), a neurotoxic aldehyde product of PUFA oxidation. Increased protein oxidation and a marked decline in oxidative sensitive enzymes, glutamine synthetase and creatinine kinase, are found in the brain in AD. Increased DNA oxidation, especially 8-hydroxy-2'-deoxyguanosine (8 OHdG) is present in the brain in AD. Immunohistochemical studies show the presence of oxidative stress products in neurofibrillary tangles and senile plaques in AD. Markers of lipid peroxidation (HNE, isoprostanes) and DNA (8-OHdG) are increased in CSF in AD. In addition, inflammatory response markers (the complement cascade, cytokines, acute phase reactants and proteases) are present in the brain in AD. These findings, coupled with epidemiologic studies showing that anti-inflammatory agents slow the progression or delay the onset of AD, suggest that inflammation plays a role in AD. Overall these studies indicate that oxidative stress and the inflammatory cascade, working in concert, are important in the pathogenetic cascade of neurodegeneration in AD, suggesting that therapeutic efforts aimed at both of these mechanisms may be beneficial. PMID- 9989457 TI - Oxidative stress in Huntington's disease. AB - It has been five years since the elucidation of the genetic mutation underlying the pathogenesis of Huntington's disease (HD) (97), however the precise mechanism of the selective neuronal death it propagates still remains an enigma. Several different etiological processes may play roles, and strong evidence from studies in both humans and animal models suggests the involvement of energy metabolism dysfunction, excitotoxic processes, and oxidative stress. Importantly, the recent development of transgenic mouse models of HD led to the identification of neuronal intranuclear inclusion bodies in affected brain regions in both mouse models and in HD brain, consisting of protein aggregates containing fragments of mutant huntingtin protein. These observations opened new avenues of investigation into possible huntingtin protein interactions and their putative pathogenetic sequelae. Amongst these studies, findings of elevated levels of oxidative damage products such as malondialdehyde, 8-hydroxydeoxyguanosine, 3-nitrotyrosine and heme oxygenase in areas of degeneration in HD brain, and of increased free radical production in animal models, indicate the involvement of oxidative stress either as a causative event, or as a secondary constituent of the cell death cascade in the disease. Here we review the evidence for oxidative damage and potential mechanisms of neuronal death in HD. PMID- 9989459 TI - Case of the month: July 1998 - 21 year old man with new-onset seizures and a temporal lobe mass. PMID- 9989458 TI - Oxidative stress and motor neurone disease. AB - The effects of oxidative stress within post mitotic cells such as neurones may be cumulative, and injury by free radical species is a major potential cause of the age-related deterioration in neuronal function seen in several neurodegenerative diseases. There is strong evidence that oxidative stress plays an important role in the pathogenesis of motor neurone disease (MND). Point mutations in the antioxidant enzyme Cu,Zn superoxide dismutase (SOD1) are found in some pedigrees with the familial form of MND. How mutations in this ubiquitous enzyme cause the relatively selective cell death of specific groups of motor neurones is not clear, although a number of hypotheses have been forwarded. These include (1) the formation of hydroxyl radicals, (2) the catalysis of reactions of the nitrogen centred oxidant species peroxynitrite, (3) toxicity of copper or zinc and (4) protein aggregation. Some experimental support for these different hypotheses has been produced by manipulating cells in culture to express the mutant SOD1 proteins and by generating transgenic mice which over-express mutant SOD1. Observations in these model systems are, in some cases at least, supported by observations made on pathological material from patients with similar SOD1 mutations. Furthermore, there are reports of evidence of free radical mediated damage to neurones in the sporadic form of MND. Several lines of evidence suggest that alterations in the glutamatergic neurotransmitter system may also play a key role in the injury to motor neurones in sporadic MND. There are several important subcellular targets, which may be preferentially impaired within motor neurones, including neurofilament proteins and mitochondria. Future research will need to identify the aspects of the molecular and physiological phenotype of human motor neurones that makes them susceptible to degeneration in MND, and to identify those genetic and environmental factors which combine to cause this disease in individuals and in familial pedigrees. PMID- 9989460 TI - Case of the month: August 1998 - 45 year old man with headache and ataxia. PMID- 9989461 TI - Case of the month: September 1998 - 18 year old male with large cystic orbital tumor. PMID- 9989462 TI - Altered calpastatin protein levels following traumatic brain injury in rat. AB - Pathological activation of the intracellular Ca2+-dependent proteases calpains may be responsible for the neuronal pathology associated with neurodegenerative diseases and acute traumas to the central nervous system. Though calpain activation has been shown definitively in traumatic brain injury (TBI), no studies have investigated calpastatin (CAST), the calpains' endogenous and specific inhibitor, after TBI. The present study examined temporal changes in CAST protein following controlled cortical impact injury in the rat. Western blot analyses of CAST in cortex and hippocampus detected two bands corresponding to molecular weights of 130 kDa [high-molecular-weight (HMW)] and 80 kDa [low molecular-weight (LMW)]. A modest decrease in the HMW band in conjunction with a significant increase in the LMW band was observed in cortex ipsilateral to the site of impact following TBI. Examination of ipsilateral hippocampus revealed an increasing trend in the LMW band after injury, while no changes were observed in the HMW band. Thus, observable changes in CAST levels appear to occur several hours after reported calpain activation and cleavage of other substrates. In addition, a new analysis was performed on previously published data examining calpain activity in the same tissue samples used in the present study. These data suggest an association between decreases in calpain activity and accumulation of LMW CAST in the ipsilateral cortex following TBI. The present study cannot exclude proteolytic processing of CAST to LMW forms. However, the absence of reciprocity between changes in LMW and HMW bands in consistent with other data suggesting that rat brain could contain different CAST isoforms. PMID- 9989464 TI - Endogenous glutathione protects cerebral endothelial cells from traumatic injury. AB - Blood-brain barrier breakdown and edema, indicative of cerebrovascular injury, are characteristic pathophysiologic outcomes following head trauma. These injuries result from both primary mechanical damage and from secondary events initiated by the traumatic insult. Free radicals are recognized as mediators of secondary injury in a number of trauma models. In this study, we used a novel in vitro model of traumatic microvascular injury to test the hypothesis that endogenous glutathione protects cerebral endothelial cells from secondary autooxidative injury following mechanical trauma. Porcine brain cerebral endothelial cells were grown in tissue culture wells with Silastic membrane bottoms, and cellular injury was induced by displacing the membrane different distances with user-defined pressure pulses from a customized device. The resultant endothelial cell injury 2 h following stretch was determined by measuring lactate dehydrogenase in the culture media. Significant stretch dependent increases in endothelial injury were elicited that depended in a nonlinear fashion on the degree of membrane displacement. Depletion of intracellular glutathione with buthionine sulfoximine (1 mM) increased the extent of traumatic endothelial cell injury by 17-56%, particularly at low to moderate levels of traumatic injury (30-40% of total endothelial cell LDH release). Conversely, traumatic injury was reduced by 22-45% when endothelial cell glutathione levels were augmented threefold (to 140+/-8 nmol/mg protein) by preincubating cells with 2 mM glutathione; the extent of protection was inversely proportional to the extent of the traumatic stretch. Traumatic endothelial cell injury was also significantly and dose-dependently attenuated (up to 40%) by treatment with the xanthine oxidase inhibitor oxypurinol (50 and 100 microM). These results demonstrate that cerebral endothelial cells are the targets of hydrogen peroxide-mediated injury secondary to trauma-induced superoxide radical formation via the xanthine oxidase pathway. The neutralization of peroxides by the endogenous glutathione redox cycle provides endothelial cells a finite capacity to reduce free radical-mediated traumatic injury; this cycle may be amenable to therapeutic manipulation to mitigate posttraumatic edema and other manifestations of vascular dysfunction. PMID- 9989463 TI - P-selectin blockade following fluid-percussion injury: behavioral and immunochemical sequelae. AB - Traumatic brain injury (TBI) can cause polymorphonuclear leukocyte (PMN) migration into brain parenchyma, mediating various cytodestructive mechanisms. We examined the effect of blocking leukocyte/endothelial cell adhesion molecules (CAMs) on the anatomic and behavioral sequelae in lateral fluid-percussion injury in rats. Monoclonal antibodies (MAb) directed against a functional (PB1.3) or nonfunctional (PNB1.6) epitope on endothelial P-selectin were used as treatments. Subjects were tested in the Morris water maze (MWM) at 7 and 14 days postinjury then immunohistochemistry was performed using antibodies that recognize ChAT, GFAP and OX-42. A second set of animals underwent myeloperoxidase (MPO) assay in the brain parenchyma and a third set was used to examine neutrophil migration using the MAb RP-3. Time in quadrant, but not escape latency or proximity improved with PB1.3 (p < 0.05). Similarly, PB1.3 reduced MPO levels after injury (p < 0.05), in the ipsilateral cortex. No significant difference occurred in neutrophil counts in cortex, corpus callosum, hippocampus, and thalamus between injured only rats and injured rats treated with PB1.3. Quantitative analysis of cholinergic cells in the medial septum showed a protective effect by PB1.3. Densitometry readings of GFAP and OX-42 immunolabeling revealed no discernible differences between the treated and untreated injured rats. Qualitatively, there was no difference in microglia or astrocyte response to treatment. Treatment with P-selectin blockade in brain-injured rats may reduce PMN migration into brain, help preserve cholinergic immunolabeling of medial septal nucleus neurons, and may alleviate mnemonic deficits. PMID- 9989465 TI - Effects of cell-permeant calcium chelators on contractility in monkey basilar artery. AB - Vasospasm after traumatic or aneurysmal subarachnoid hemorrhage is associated with smooth muscle contraction, a process that results in part from increased intracellular calcium in smooth muscle cells. These experiments tested the hypothesis that chelation of intracellular calcium with the cell-permeant calcium chelator, 1,2-bis-(2-aminophenoxy)ethane-N,N,N',N'-tetracetic acid acetoxymethyl ester (BAPTA-AM), decreases smooth muscle contraction in response to agents that cause contraction by increasing intracellular calcium. Effects of BAPTA-AM on vasoconstriction induced by KCl, prostaglandin F2alpha (PGF2alpha), caffeine, and erythrocyte hemolysate were tested on monkey basilar artery under isometric tension. BAPTA-AM, 30 and 100 micromol/L, caused a significant decrease in resting tension in rings with and without endothelium (30 micromol/L; 8+/-6% [n.s.] and 14+/-5%, 100 micromol/L; 19+/-3% and 32+/-6%,p < 0.05, paired t test). Contractions to caffeine were significantly decreased by 30 micromol/L BAPTA-AM and were abolished at 100 micromol/L in rings with and without endothelium (p < 0.05). BAPTA-AM, 100 micromol/L, competitively inhibited contractions to PGF2alpha. BAPTA-AM, 100 micromol/L, significantly decreased the maximum contractions to KCI in rings with and without endothelium (p < 0.05). There were no significant effects of BAPTA-AM on contractions induced by hemolysate in rings with endothelium but in rings without endothelium, BAPTA-AM, 100 micromol/L, significantly inhibited contractions. In rings with endothelium contractions to hemolysate could be significantly reduced by BAPTA-AM plus indomethacin or indomethacin alone, suggesting that hemolysate releases an eicosanoid from the endothelium by a pathway that is not inhibited by BAPTA. These results suggest that the ability of BAPTA-AM to inhibit smooth muscle contractions will depend on the agonists mediating the contraction. In response to erythrocyte hemolysate, loading of endothelial cells with BAPTA-AM increases the release of a vasoconstricting eicosanoid from these cells that counteracts the decreased contraction caused by loading of smooth muscle cells with BAPTA-AM. PMID- 9989466 TI - Distribution and latency of muscle responses to transcranial magnetic stimulation of motor cortex after spinal cord injury in humans. AB - Noninvasive transcranial magnetic stimulation (TMS) of the motor cortex was used to evoke electromyographic (EMG) responses in persons with spinal cord injury (n = 97) and able-bodied subjects (n = 20, for comparative data). Our goal was to evaluate, for different levels and severity of spinal cord injury, potential differences in the distribution and latency of motor responses in a large sample of muscles affected by the injury. The spinal cord injury (SCI) population was divided into subgroups based upon injury location (cervical, thoracic, and thoracolumbar) and clinical status (motor-complete versus motor-incomplete). Cortical stimuli were delivered while subjects attempted to contract individual muscles, in order to both maximize the probability of a response to TMS and minimize the response latency. Subjects with motor-incomplete injuries to the cervical or thoracic spinal cord were more likely to demonstrate volitional and TMS-evoked contractions in muscles controlling their foot and ankle (i.e., distal lower limb muscles) compared to muscles of the thigh (i.e., proximal lower limb muscles). When TMS did evoke responses in muscles innervated at levels caudal to the spinal cord lesion, response latencies of muscles in the lower limbs were delayed equally for persons with injury to the cervical or thoracic spinal cord, suggesting normal central motor conduction velocity in motor axons caudal to the lesion. In fact, motor response distribution and latencies were essentially indistinguishable for injuries to the cervical or thoracic (at or rostral to T10) levels of the spine. In contrast, motor-incomplete SCI subjects with injuries at the thoracolumbar level showed a higher probability of preserved volitional movements and TMS-evoked contractions in proximal muscles of the lower limb, and absent responses in distal muscles. When responses to TMS were seen in this group, the latencies were not significantly longer than those of able-bodied (AB) subjects, strongly suggestive of "root sparing" as a basis for motor function in subjects with injury at or caudal to the T11 vertebral body. Both the distribution and latency of TMS-evoked responses are consistent with highly focal lesions to the spinal cord in the subjects examined. The pattern of preserved responsiveness predominating in the distal leg muscles is consistent with a greater role of corticospinal tract innervation of these muscles compared to more proximal muscles of the thigh and hip. PMID- 9989467 TI - Spasticity in rats with sacral spinal cord injury. AB - We have investigated sacral spinal cord lesions in rats with the goal of developing a rat model of muscular spasticity that is minimally disruptive, not interfering with bladder, bowel, or hindlimb locomotor function. Spinal transections were made at the S2 sacral level and, thus, only affected the tail musculature. After spinal transection, the muscles of the tail were inactive for 2 weeks. Following this initial period, hypertonia, hyperreflexia, and clonus developed in the tail, and grew more pronounced with time. These changes were assessed in the awake rat, since the tail is readily accessible and easy to manipulate. Muscle stretch or cutaneous stimulation of the tail produced muscle spasms and marked increases in muscle tone, as measured with force and electromyographic recordings. When the tail was unconstrained, spontaneous or reflex induced flexor and extensor spasms coiled the tail. Movement during the spasms often triggered clonus in the end of the tail. The tail hair and skin were extremely hyperreflexive to light touch, withdrawing quickly at contact, and at times clonus could be entrained by repeated contact of the tail on a surface. Segmental tail muscle reflexes, e.g., Hoffman reflexes (H-reflexes), were measured before and after spinalization, and increased significantly 2 weeks after transection. These results suggest that sacral spinal rats develop symptoms of spasticity in tail muscles with similar characteristics to those seen in limb muscles of humans with spinal cord injury, and thus provide a convenient preparation for studying this condition. PMID- 9989468 TI - Dual role for nitric oxide in dynorphin spinal neurotoxicity. AB - The pharmacological effects of nitric oxide synthase (NOS) inhibitors, NO donor, and NOS substrate on dynorphin(Dyn) A(1-17) spinal neurotoxicity were studied. Intrathecal (i.t.) pretreatment with both 7-nitroindazole 1 micromol, a selective neuronal constitutive NOS (ncNOS) inhibitor, and aminoguanidine 1 micromol, a selective inducible NOS (iNOS) inhibitor, 10 min prior to i.t. Dyn A(1-17) 20 nmol significantly ameliorated Dyn-induced neurological outcome. Both 7 nitroindazole and aminoguanidine significantly antagonized the increases of cNOS and iNOS activities measured by conversion of 3H-L-arginine to 3H-L-citrulline in the ventral spinal cord, and blocked the Dyn-induced increases of ncNOS immunoreactivity in the ventral horn cells 4 h after i.t. Dyn A(1-17) 20 nmol. Pretreatment with Nomega-nitro-L-arginine methyl ester (L-NAME) 1 micromol, a cNOS inhibitor nonselective to both ncNOS and endothelial NOS (ecNOS), did not antagonize Dyn A(1-17) 20 nmol-induced permanent paraplegia but aggravated Dyn A(1-17) 10 nmol-induced transient paralysis and caused permanent paraplegia. Pretreatment with L-NAME 1 micromol 10 min before i.t. Dyn A(1-17) 1.25 and 2.5 nmol, which produced no significant motor dysfunction alone, induced transient paralysis in seven out of 12 and five out of seven rats, respectively. L-NAME 1 micromol plus Dyn A(1-17) 10 nmol induced ncNOS-immunoreactivity expression in ventral horn cells. Both low and high doses of aminoguanidine (0.2-30 micromol) did not affect spinal motor function, but high doses of L-NAME (5-20 micromol) induced dose-dependent hindlimb and tail paralysis associated with spinal cord injury in normal rats. Pretreatment with low-dose Spermine NONOate, a controlled NO releaser, 0.1 and 0.5 micromol 10 min before i.t. Dyn A(1-17) 20 nmol, significantly prevented Dyn spinal neurotoxicity, and high-dose Spermine NONOate 2 micromol i.t. per se induced transient and incomplete paraplegia. But pretreatment with L-Arg 10 micromol 10 min before Dyn A(1-17) 20 nmol produced only partial blockade of Dyn-induced paraplegia. These results demonstrated that relatively specific inhibition of ncNOS and iNOS block Dyn-induced increases in cNOS and iNOS activities and ncNOS-immunoreactivity in ventral spinal cord, but nonspecific inhibition of ncNOS and ecNOS aggravated Dyn spinal neurotoxicity. It suggested that both ncNOS and iNOS play an important role, but ecNOS might be beneficial in Dyn spinal neurotoxicity. Moderate production of NO (at vascular level) has an apparently neuroprotective effect, and overproduction of NO (at cellular level) induces neurotoxicity. PMID- 9989469 TI - Peripheral nerve injection injury with antiemetic agents. AB - Antiemetics are widely used drugs, frequently administered to alleviate postoperative and postchemotherapeutic nausea and vomiting. While antiemetics do not induce peripheral neurotoxicity when administered systemically, it is not known whether peripheral nerve injury can occur as a result of inadvertent intraneural injection during intramuscular administration. The purpose of this study was to characterize the neurotoxic effect of three commonly used antiemetic agents (promethazine, dimenhydrinate, and prochlorperazine) as compared to saline in the rat sciatic nerve model. Intrafascicular and extrafascicular injection as well as direct application of the antiemetic drugs were performed. Nerves were harvested at 2 weeks postoperatively for histology and morphometry, with an additional sacrifice point at 8 weeks for the intrafascicular injection group. Injection injuries caused by antiemetic drugs differed depending on the agent injected and the location of injection. Extrafascicular injection and direct application caused no damage. Intrafascicular injection caused diffuse axonal injury in the promethazine and dimenhydrinate groups, while prochlorperazine caused only focal injury. Regeneration was prominent at 8 weeks in all intrafascicular injection groups in this rat model. Prochlorperazine thus appears to be less neurotoxic when injected intraneurally and should preferentially be used for intramuscular injections. PMID- 9989470 TI - Effects of ibuprofen on arylamine N-acetyltransferase activity in human colon tumor cells. AB - The inhibition of arylamine N-acetyltransferase (NAT) activity by ibuprofen was determined in a human colon tumour (adenocarcinoma) cell line. Two assay systems were employed, one with cellular cytosols (9000 g supernatant) and the other with intact colon tumour cell suspensions. The NAT activity in a human colon tumour cell line was inhibited by ibuprofen in a dose-dependent manner in both systems, i.e. the greater the concentration of ibuprofen in the reaction, the greater the inhibition of NAT activities in both systems. The data also indicated that ibuprofen decreases the apparent Km and Vmax of NAT enzyme from human colon tumour cells in both systems examined. This report is the first demonstration to show that ibuprofen affects human colon tumour cell NAT activity. PMID- 9989471 TI - Ochratoxicosis: prevention of developmental toxicity by L-methionine in rats. AB - L-Methionine was found to inhibit the developmental toxicity induced by ochratoxin A (OA) in pregnant female rats. The fetuses had significantly lower weights. Dams and fetuses treated with OA had visceral and skeletal anomalies, while combined treatment with L-methionine and OA showed no significant changes when compared to the control. Histopathological examinations revealed that OA caused alterations in liver, kidney and vagina of pregnant rats, whereas methionine supplementation provided partial protection for renal and liver tissue. PMID- 9989472 TI - Hexachlorocyclohexane-induced behavioural and neurochemical changes in rat. AB - Effect of chronic oral exposure (10 and 20 mg kg(-1) body wt. for 7, 15 and 30 days) to hexachlorocyclohexane (HCH) on open-field behaviour and activities of cerebral Na+,K+-ATPase, Mg2+-ATPase and acetylcholinesterase (AChE) of rat was evaluated. Motor and grooming activities were altered, whereas vertical exploratory activity was unaffected by HCH. Activities of Na+,K+-ATPase, Mg2+ ATPase and AChE were inhibited significantly by the pesticide. The results suggest that HCH induces impairment of the enzymes involved in synaptic activity, resulting in behavioural alterations. PMID- 9989473 TI - Inhalation of substance P and thiorphan: acute toxicity and effects on respiration in conscious guinea pigs. AB - Substance P is a tachykinin and a biologically active neuropeptide. The peptide produces salivation, neuronal excitation, vasodilatation, increased vascular permeability and contraction of smooth muscles in the respiratory tract. The study was designed to evaluate the acute effects in guinea pigs of inhaled aerosolized Substance P (SP). Apart from the acute toxic effect of the peptide, the distribution in different organs was also investigated. The acute inhalation toxicity of SP (LC50, 15 min) when co-administrated with the neutral endopeptidase inhibitor thiorphan was 368 microg m(-3). The peptide caused an increase in respiratory rate proceeding a decrease in tidal volume. As the exposure proceeded, a decrease in both respiratory rate and further decreases in tidal volume were observed until either the animal died or the exposure was terminated. The decreases in respiratory rate and tidal volume were probably due to bronchoconstriction caused by SP. Eighteen per cent of the inhaled amount of radioactive SP was retained in the body, and the highest concentrations of radioactivity were found in the kidney, lung and liver. Substance P in combination with thiorphan administered as an aerosol is extremely toxic and highly potent. Exposure to the substance at extremely low air concentrations may result in incapacitation in humans. PMID- 9989474 TI - Exposure of Rana ridibunda to lead I. Study of lead accumulation in various tissues and hepatic delta-aminolevulinic acid dehydratase activity. AB - There are few data at present on the impact of lead (Pb) on amphibians, although declines in amphibian populations due to man-made changes in the environment have been recorded in recent years. The impact of Pb in adult frogs, Rana ridibunda, was therefore examined. Animals were exposed to 14 mg l(-1) (ppm) aqueous Pb [as Pb(NO3)2] for 4, 10 and 30 days. The chosen Pb concentration corresponded to one tenth of the 96-h LC50 value for Pb (138.18 ppm). We measured the Pb content of the liver, kidneys, ventral skin and gastrointestinal (GI) tract, and the activity of hepatic delta-aminolevulinic acid dehydratase (delta-ALA-D). Gross morphological characteristics of the frogs were not affected by Pb accumulation in their tissues. At the end of the 30 days of exposure all tissues accumulated Pb. The accumulation of Pb in the liver, kidneys and ventral skin was correlated positively with the time of exposure. The Pb concentration in the GI tract reached a plateau at day 10 and there was no significant increase of Pb in the liver after day 10, suggesting excretion of Pb. The activity of hepatic delta-ALA D decreased by 90% on day 30 compared to control values. The decrease of hepatic delta-ALA-D activity was correlated negatively with the concentration of Pb in liver and the time of exposure. This study suggests that the hepatic delta-ALA-D activity can be used as a biomarker of Pb intoxication for this species. PMID- 9989475 TI - Acridine-induced subcellular and functional changes in isolated human hepatocytes in vitro. AB - Acridines are nucleic acid intercalating compounds with properties relating to the complexity of their structure. Tetrahydroaminoacridine (tacrine, Cognex), a simple acridine, is a reversible inhibitor of cholinesterase activity available for the symptomatic treatment of Alzheimer's disease. Tacrine therapy causes sporadic elevations of aminotransferases in humans, and tacrine alters protein synthesis and ribosomal structure under short-term in vitro exposures in isolated hepatocytes from humans and other species. There is no clear relationship between transaminase elevation and liver damage in humans, and prolonged drug exposure to animals does not result in hepatic insult. Subcellular alterations have been described in isolated human and rodent hepatocytes, including degranulation and vesiculation of the endoplasmic reticulum (ER), aggregation of electron-dense structures within the ER, altered nuclei and nucleoli and detrimental structural and functional effects to mitochondria. Whether these changes in hepatocyte morphology and function are unique to tacrine or not is unknown, as human hepatocytes exposed to more complex acridines have not been characterized. In this study, we extended the results of in vitro studies with tacrine to acridine orange, 9-aminoacridine, quinacrine and proflavin. In primary human hepatocytes, these compounds caused a similar reduction of mitochondrial membrane potential with parallel ultrastructural changes. The 1-hydroxy and 7-hydroxy tacrine metabolites, acridine hydrochloride and acridine 9-carboxylic acid, and the non acridine cholinesterase inhibitor eserine, did not induce characteristic subcellular ER changes but damaged mitochondria structure, reduced mitochondrial membrane potential and were cytotoxic. These data indicate that the tacrine-like subcellular changes in hepatocytes are reproducible with other acridines and cause mitochondrial dysfunction in human hepatocytes. PMID- 9989476 TI - Partial and weak oestrogenicity of the red wine constituent resveratrol: consideration of its superagonist activity in MCF-7 cells and its suggested cardiovascular protective effects. AB - It was recently reported that the red wine phytoestrogen resveratrol (RES) acts as a superagonist to oestrogen-responsive MCF-7 cells. This activity of RES was speculated to be relevant to the 'French paradox' in which moderate red wine consumption is reported to yield cardiovascular health benefits to humans. We report here that RES binds to oestrogen receptors (ER) isolated from rat uterus with an affinity approximately 5 orders of magnitude lower than does either the reference synthetic oestrogen diethylstilboestrol (DES) or oestradiol (E2). In comparison with E2 or DES, RES is only a weak and partial agonist in a yeast hER alpha transcription assay and in cos-1 cell assays employing transient transfections of ER-alpha or ER-beta associated with two different ER-response elements. Resveratrol was also concluded to be inactive in immature rat uterotrophic assays conducted using three daily administrations of 0.03-120 mgkg( 1)/day(-1) RES (administered by either oral gavage or subcutaneous injection). These data weaken the suggestion that the oestrogenicity of RES may account for the reported cardiovascular protective effects of red wine consumption, and they raise questions regarding the extent to which oestrogenicity data derived for a chemical using MCF-7 cells (or any other single in vitro assay) can be used to predict the hormonal effects likely to occur in animals or humans. PMID- 9989477 TI - Role of SAM-dependent thiol methylation in the renal toxicity of several solvents in mice. AB - The role of S-adenosylmethionine (SAM)-dependent thiol methylation in the nephrotoxicity of seven industrial solvents was studied in mice. The seven following solvents were utilized: bromobenzene (BB), styrene (STY), tetrachloroethylene (TTCE), trichloroethylene (TCE), 1,1-dichloroethylene (DCE), 1,2-dichloroethane (DCA) and hexachlorobutadiene (HCB). The experimental model comprised mice pretreated with periodate oxidized adenosine (ADOX) (100 micromol kg(-1) i.p.) 30 min before injection of solvents. In the first 4 h after ADOX treatment, the SAM levels were about fourfold higher than controls for the liver and kidney. The S-adenosylhomocysteine (SAH) levels were increased by factors of 11 and 14 and the SAM/SAH ratios were decreased by factors of 3 and 10 for the liver and kidney, respectively. These results show that ADOX treatment probably induces an inhibition of methyltransferase SAM-dependent in the liver and kidney and thus decreases the methylation capabilities. A single oral administration of BB (500 or 800 mg kg(-1)), TTCE (3500 or 4000 mg kg(-1)), TCE (3000 or 3500 mg kg(-1)) or STY (400 or 600 mg kg(-1)) did not induce renal toxicity, evaluated by the percentage of damaged tubules compared to controls. On the other hand, the three solvents DCE, HCB and DCA were nephrotoxic and the percentage of damaged tubules observed for each solvent was significantly different from the value of <1.8% for controls: 19% and 40% for DCE (130 and 200 mg kg(-1)), 50% and 46% for HCB (80 and 100 mg kg(-1)) and 5.1% and 7.6% for DCA (1000 and 1500 mg kg(-1)). The ADOX treatment in the mice did not modify the renal toxicity of the seven solvents. Thus, their renal toxicity, when it existed, was probably independent of the SAM-dependent thiolmethyltransferase activity in the mice. The results of this study are discussed from two viewpoints. The first concerns the general considerations on inhibition of thiol methyltransferase activities in mice and the second is related to the different solvents that are evoked individually. PMID- 9989478 TI - Profile of reactive oxygen species generation and antioxidative mechanisms in the maturing rat kidney. AB - The antioxidative potential and reactive oxygen species generation were assessed in rat kidney during early critical periods of development and maturation. Superoxide anion generation was found to be low in kidney during early postnatal days of development, whereas hydrogen peroxide levels remained unaltered during development. The levels of thiobarbituric acid reactive substances and protein carbonyls in developing kidney were higher during early postnatal days, up to 26 days after birth, compared to the adult levels. Kidney sulphydryl contents were significantly less during early periods (9 days postnatally) of development compared to adults but attain adult value by postnatal day 26. The levels of ascorbic acid and ceruloplasmin were also higher in developing kidney than in adults. Among enzymic antioxidants, the levels of glutathione peroxidase (GPx) enzyme in developing kidney were high during the early developmental period of the study as compared to adults; however, superoxide dismutase (SOD), catalase (CAT) and glutathione reductase (GR) were found to be significantly low at early postnatal days up to 16 days of age, which subsequently attained maturational level by the age of 26 days. The levels of antioxidant enzymes and sulphydryl contents in the developing kidney during early periods after birth are low but they increase subsequently with increasing age. Therefore, the present finding suggests that immature kidneys are in a highly dynamic stage of development during the early period and are equipped with antioxidative defence mechanisms that may have a predominant role in protecting against oxidative challenge. PMID- 9989479 TI - Is thallium-induced nephrotoxicity in rats connected with riboflavin and/or GSH?- reconsideration of hypotheses on the mechanism of thallium toxicity. AB - Adult female Wistar rats (Han:Wist) were injected with 2 mg of Tl2SO4 per 100 g body weight. Parameters of nephrotoxicity were urinary volume and protein excretion as well as blood urea nitrogen concentration. Thallium concentrations were determined in renal cortex and medulla. There was no effect of different schedules of vitamin B2 (riboflavin) treatment on thallium nephrotoxicity. Glutathione (GSH) concentration was not decreased by thallium in renal cortex or in medulla. The increase of GSH concentration in renal tissue by N-acetylcysteine pretreatment did not influence thallium nephrotoxicity. Buthionine sulphoximine diminished thallium nephrotoxicity by a significant decrease of thallium concentration in renal medulla, which was caused by enhanced urinary excretion of thallium. From our investigations we conclude that there is no relation between thallium-induced nephrotoxicity and riboflavin and/or GSH. PMID- 9989480 TI - Effect of pyrethroid-based liquid mosquito repellent inhalation on the blood brain barrier function and oxidative damage in selected organs of developing rats. AB - Pesticides have been implicated in various neurological disorders in humans and experimental animals. Our earlier studies have demonstrated a high vulnerability of developing blood-brain barrier (BBB) towards very low level exposure of quinalphos, cypermethrin and lindane. Earlier it has been observed that a cypermethrin-induced increase in the BBB permeability of neonatal rats was found to be persistent, requiring a longer period of withdrawal for complete recovery. These observations lead us to investigate the effect of a commonly available liquid mosquito repellent (MR) containing a pyrethroid compound, allethrin (3.6% w/v), on the functional integrity of the developing BBB and on certain parameters of oxidative damage in brain, liver and kidney. Two-day-old rat pups were allowed to inhale the MR (18 h per day) for 8 days (postnatal days (PND) 2-9). Rats exposed to MR were further withdrawn from the exposure for 8 days (PND 10-17) to study whether the changes induced following inhalation are reversible. Results of the study have shown a significant increase in the BBB permeability (45%) of the MR-exposed rat pups to a micromolecular tracer, sodium fluorescein (mol. wt. 376), used for the quantitative assessment of the BBB permeability, suggesting a delayed maturity of the BBB system. Brain glutathione (GSH) levels were also decreased (17%) in the exposed individuals. The oxidatively damaged end-products of lipids, measured as lipid hydroperoxides and conjugated dienes, were found to be increased in brain (42%, 16%), liver (34%, 20%) and kidney (68%, 29%), respectively. The oxidative product of protein, measured as protein carbonyls, was also increased significantly in liver (43%) and kidney (16%) of the MR exposed rat pups as compared to age-matched controls. The biochemical changes that occurred in the BBB permeability and the oxidatively damaged end-products following MR inhalation in neonatal rats were, however, found to be completely recovered except for an increase in brain GSH (28%) level. The results suggest the possibility of health risk due to exposure to pesticide-based mosquito repellents, especially when exposure takes place in individuals at an early age. PMID- 9989481 TI - Introduction: immunotherapy for multiple myeloma--insights and advances. PMID- 9989482 TI - Management of multiple myeloma today. AB - Multiple myeloma is almost invariably fatal despite a wide variety of chemotherapeutic and supportive treatment options. There are several unresolved problems with existing approaches, including the specific indications for treatment; the optimal combination of agents and doses; and the type, frequency, and timing of high-dose therapy and stem-cell transplantation. High-dose chemotherapy followed by stem-cell transplantation produces higher remission rates, but patients rarely, if ever, are cured by a single regimen. Allogeneic hematopoietic stem-cell transplantations offer a potential graft-versus-myeloma (GVM) effect. Researchers are focusing efforts on improving the safety of transplant procedures, increasing response rates to ablative therapy, and testing novel posttransplant options to improve outcomes. The newly devised National Comprehensive Cancer Network (NCCN) guidelines for treating multiple myeloma are also discussed. PMID- 9989483 TI - Initiation and maintenance of multiple myeloma. AB - A recently identified herpesvirus, human herpesvirus-8 (HHV-8), also known as Kaposi's sarcoma (KS)-associated herpesvirus, has been found in nonmalignant bone marrow dendritic cells of patients with multiple myeloma. The virus is also detectable in the peripheral blood of most patients; its absence suggests earlier stage disease. HHV-8 is not detected in the blood of family members and sexual partners of myeloma patients. Sequencing of HHV-8 open-reading frames (ORFs) shows differences between individual myeloma patients, as well as between myeloma patients and those with other HHV-8-related malignancies. Consistent expression of the viral homolog of both interferon regulatory factor (IRF) and interleukin-8 receptor (IL-8R) suggests a possible role for these transforming viral genes in the pathogenesis of myeloma. Detailed analysis of myeloma cell lines has shown that myeloma is characterized by frequent chromosome translocations involving the switch regions of the immunoglobulin heavy-chain (IgH) locus on 14q32. The three partner chromosomes most commonly involved are 11q13 (cyclin D1), 4p16 (FGFR3), and 16q23 (c-maf). Mutations have also been identified in N- and K-ras and, less frequently, involving p53. Monosomy 13q is common. These findings have implications for immunotherapy. Angiogenesis increases with progressive disease and appears to be a prognostic factor. In at least one patient, this process appears to have been reversed with thalidomide therapy. The underlying mechanisms for the increased vascularization in myeloma have not been identified, and several possibilities have been proposed. PMID- 9989484 TI - Role of cytokines in multiple myeloma. AB - Recent research in the biology of multiple myeloma (MM) has produced new insight into the factors that control the growth and survival of myeloma cells. In particular, there is a greater appreciation of the pathogenic role of the cytokines, such as interleukin-6 (IL-6) and IL-1beta in the conversion of monoclonal gammopathy of undetermined significance (MGUS) to MM and in the proliferation and survival of myeloma cells. Infection of dendritic cells with Kaposi's sarcoma-associated herpesvirus (KSHV), which secretes a viral homolog of IL-6, may also be a factor. As a direct application of recent laboratory observations, several immune-based treatment strategies are being developed. PMID- 9989485 TI - Presentation of tumor antigens. AB - Dendritic cells, with their extraordinary capacity for initiating primary and secondary T-lymphocyte responses, may be pivotal in the development of immunotherapeutic strategies for multiple myeloma. Although host lymphocytes are able to recognize tumor-associated antigens (TAAs), many tumors are able to avoid dendritic cell-mediated immune surveillance. One reason may be that the tumor environment inhibits the maturation and activation of dendritic cells. A recently developed strategy to use dendritic cells in immunotherapy involves removing them from the tumor, pulsing them in vitro with antigen, and reinfusing them into the patient to generate responding T cells in vivo. Methods for reliably obtaining dendritic cells for therapeutic use are currently being investigated. Among other efforts to induce T-cell-mediated immunity against cancer, the presentation of tumor antigens by the tumor cells themselves is being investigated. Issues to be resolved include defects of antigen presentation by tumor cells and whether all cells present the same set of peptides. Moreover, as long as all the tumor antigens have not been identified, the tumor cell itself remains the primary source of unknown antigens and, therefore, is a worthwhile subject for study. Phase I trials of immunotherapy using adenovirus-infected autologous plasma cells have recently been undertaken. The adenoviral vectors carry genes with therapeutic potential, including interleukin-2 (IL-2), interleukin-12, and B7-1. Initial results showed that the vector can be readily detected in tumor cells at 13 days postinjection, and IL-2 expression was evident at 7 days. The chief side effect reported was inflammation. PMID- 9989486 TI - Adoptive T-cell therapy. AB - Adoptive immunotherapy, or the transfer of immunocompetent cells, has been shown to be a promising new strategy for treatment of a variety of malignancies, including leukemia and non-Hodgkin's lymphoma. The possibility that it may likewise benefit patients with multiple myeloma is now being explored by researchers in Europe and the United States. Two alternatives, one using donor leukocyte infusions (DLIs) and the other using autologous T cells, are described. In the Netherlands, researchers studied the use of DLIs in 17 patients with multiple myeloma who relapsed after bone marrow transplant (BMT). Of 16 evaluable patients, 10 (62%) responded, with six (37%) achieving a complete response (CR). After a median follow-up duration of 28 months, five patients relapsed and five remained in remission. Graft-versus-host disease (GVHD) developed in nine patients. In the United States, adoptive immunotherapy is currently being tested in eight patients with chemotherapy-resistant lymphoma. Autologous T cells were obtained prior to BMT and expanded using an anti-CD3/CD28 culture system. After BMT, the cells were reinfused into the patient. At approximately day 14, granulocyte levels began to recover in the six evaluable patients, and levels remained relatively stable over the posttreatment course. Two patients developed severe autoimmune toxicity, which responded to treatment in one and resolved spontaneously in the other. PMID- 9989487 TI - Antibody therapy for treatment of multiple myeloma. AB - Monoclonal antibody therapy has emerged as a viable treatment option for patients with lymphoma and some leukemias. It is now beginning to be investigated for treatment of multiple myeloma. There are relatively few surface antigens on the plasma cells that are suitable for antibody-directed treatment. Possible molecules include HM1.24, CD38, ICAM-1 (CD54), CD40, CD45, CD20, and syndecan 1. There is now some clinical experience with anti-CD38 antibody in lymphoma and myeloma. However, to date, there has been minimal clinical activity observed. Additional antibodies are entering clinical trials. A new approach involves the generation of an anti-CD38 single-chain variable fragment (scFv) construct that acts as the carrier of a toxin gene instead of being conjugated directly to the toxin itself. It is hoped that expression of the toxin by CD38+ plasma cells will promote suicide of the malignant cells without affecting normal cells or generating an immunologic response to the toxin. Ongoing clinical trials are also attempting to target B-cell antigens such as CD20. Although CD20 is present only on 20% of myeloma cells, it may be present on myeloma precursor cells. This treatment has met with success in follicular lymphoma and is now being evaluated in clinical trials in both Europe and the United States for myeloma. Although these clinical trials are in very early stages, researchers are beginning to understand that antibody therapy can be used not only as a carrier molecule of radioisotopes and toxins, but also as molecules that can trigger tumor cells and promote growth arrest or apoptosis. PMID- 9989488 TI - Idiotypic vaccination as therapy for multiple myeloma. AB - Although advances in the treatment of multiple myeloma have been made using high dose chemotherapy with subsequent autologous stem-cell transplantation, recurrence of the underlying disease almost invariably occurs. One proposed strategy to increase survival is tumor-specific activation of the immune system via idiotypic protein vaccination. Current issues to be resolved in the development of this approach include optimal vaccine formulation, appropriate assays to monitor treatment results, and timing of vaccine administration. Several clinical trials of idiotypic vaccines are currently being conducted in the United States and Europe. Initial results support the use of these vaccines as adjunct therapy in patients with multiple myeloma after high-dose chemotherapy and transplantation. PMID- 9989489 TI - DNA vaccination against multiple myeloma. AB - A variety of approaches to antitumor therapy are currently being explored that use both antigen-encoding DNA and noncoding nucleotides as a component of gene vaccination. Among the specific strategies reviewed are a construct that fuses a single-chain variable fragment (scFv) that incorporates both the variable-region genes necessary to encode the idiotypic determinants with fragment C (FrC) of tetanus toxin; a novel vector system using herpes simplex virus 1 (HSV-1) for in vivo gene delivery; the possibility of eliciting hyperacute xenograft response to treat human cancer; and the use of gene gun-mediated granulocyte-macrophage colony-stimulating factor (GM-CSF) cDNA-based tumor cell vaccines. The protection provided by DNA vaccination against viral diseases such as influenza suggested a role for such vaccines against cancer. However, unlike vaccines against infectious diseases, cancer vaccines are therapeutic, rather than prophylactic. With multiple myeloma, for example, it is possible that the optimal timing of administration of such a vaccine is during a remission that has been induced by traditional therapies, to eliminate residual disease. DNA cancer vaccines are designed to activate immune responses to tumor antigens to which the immune system has already been exposed. To do so, the vaccines must first overcome immune tolerance that may have already developed to the tumor. There is increasing evidence that tumor antigens, unlike viral or bacterial antigens, do not consistently activate an immune response. One major factor in determining whether a reaction occurs appears to be whether antigen presentation is accompanied by danger signals. With viral or bacterial infection, the accompanying tissue destruction and inflammation produce costimulatory signals that promote T-cell activation. However, inflammatory and tissue-destructive processes are absent during initial tumor transformation. The typical outcome may be immunologic tolerance. PMID- 9989490 TI - From TCR engagement to T cell activation: a kinetic view of T cell behavior. PMID- 9989491 TI - Adaptors and molecular scaffolds in immune cell signaling. PMID- 9989492 TI - The actin cytoskeleton and lymphocyte activation. PMID- 9989493 TI - Transcription factors in lymphocyte development--T and B cells get together. PMID- 9989494 TI - Identification of a neural stem cell in the adult mammalian central nervous system. AB - New neurons are continuously added in specific regions of the adult mammalian central nervous system. These neurons are derived from multipotent stem cells whose identity has been enigmatic. In this work, we present evidence that ependymal cells are neural stem cells. Ependymal cells give rise to a rapidly proliferating cell type that generates neurons that migrate to the olfactory bulb. In response to spinal cord injury, ependymal cell proliferation increases dramatically to generate migratory cells that differentiate to astrocytes and participate in scar formation. These data demonstrate that ependymal cells are neural stem cells and identify a novel process in the response to central nervous system injury. PMID- 9989495 TI - Bcl10 is involved in t(1;14)(p22;q32) of MALT B cell lymphoma and mutated in multiple tumor types. AB - MALT B cell lymphomas with t(1;14)(p22;q32) showed a recurrent breakpoint upstream of the promoter of a novel gene, Bcl10. Bcl10 is a cellular homolog of the equine herpesvirus-2 E10 gene: both contain an amino-terminal caspase recruitment domain (CARD) homologous to that found in several apoptotic molecules. Bcl10 and E10 activated NF-kappaB but caused apoptosis of 293 cells. Bcl10 expressed in a MALT lymphoma exhibited a frameshift mutation resulting in truncation distal to the CARD. Truncated Bcl10 activated NF-kappaB but did not induce apoptosis. Wild-type Bcl10 suppressed transformation, whereas mutant forms had lost this activity and displayed gain-of-function transforming activity. Similar mutations were detected in other tumor types, indicating that Bcl10 may be commonly involved in the pathogenesis of human malignancy. PMID- 9989496 TI - Molecular mechanisms of bacterial virulence elucidated using a Pseudomonas aeruginosa-Caenorhabditis elegans pathogenesis model. AB - The human opportunistic pathogen Pseudomonas aeruginosa strain PA14 kills Caenorhabditis elegans. Using systematic mutagenesis of PA14 to identify mutants that fail to kill C. elegans and a C. elegans mutant that lacks P-glycoproteins, we identified phenazines, secreted P. aeruginosa pigments, as one of the mediators of killing. Analysis of C. elegans mutants with altered responses to oxidative stress suggests that phenazines exert their toxic effects on C. elegans through the generation of reactive oxygen species. Finally, we show that phenazines and other P. aeruginosa factors required for C. elegans killing are also required for pathogenesis in plants and mice, illustrating that this model tackles the dual challenges of identifying bacterial virulence factors as well as host responses to them. PMID- 9989497 TI - A molecular mechanism regulating rhythmic output from the suprachiasmatic circadian clock. AB - We examined the transcriptional regulation of the clock-controlled arginine vasopressin gene in the suprachiasmatic nuclei (SCN). A core clock mechanism in mouse SCN appears to involve a transcriptional feedback loop in which CLOCK and BMAL1 are positive regulators and three mPeriod (mPer) genes are involved in negative feedback. We show that the RNA rhythm of each mPer gene is severely blunted in Clock/Clock mice. The vasopressin RNA rhythm is abolished in the SCN of Clock/Clock animals, leading to markedly decreased peptide levels. Luciferase reporter gene assays show that CLOCK-BMAL1 heterodimers act through an E box enhancer in the vasopressin gene to activate transcription; this activation can be inhibited by the mPER and mTIM proteins. These data indicate that the transcriptional machinery of the core clockwork directly regulates a clock controlled output rhythm. PMID- 9989498 TI - Kin I kinesins are microtubule-destabilizing enzymes. AB - Using in vitro assays with purified proteins, we show that XKCM1 and XKIF2, two distinct members of the internal catalytic domain (Kin I) kinesin subfamily, catalytically destabilize microtubules using a novel mechanism. Both XKCM1 and XKIF2 influence microtubule stability by targeting directly to microtubule ends where they induce a destabilizing conformational change. ATP hydrolysis recycles XKCM1/XKIF2 for multiple rounds of action by dissociating a XKCM1/ XKIF2-tubulin dimer complex released upon microtubule depolymerization. These results establish Kin I kinesins as microtubule-destabilizing enzymes, distinguish them mechanistically from kinesin superfamily members that use ATP hydrolysis to translocate along microtubules, and have important implications for the regulation of microtubule dynamics and for the intracellular functions and evolution of the kinesin superfamily. PMID- 9989499 TI - High-resolution model of the microtubule. AB - A high-resolution model of the microtubule has been obtained by docking the crystal structure of tubulin into a 20 A map of the microtubule. The excellent fit indicates the similarity of the tubulin conformation in both polymers and defines the orientation of the tubulin structure within the microtubule. Long C terminal helices form the crest on the outside of the protofilament, while long loops define the microtubule lumen. The exchangeable nucleotide in beta-tubulin is exposed at the plus end of the microtubule, while the proposed catalytic residue in alpha-tubulin is exposed at the minus end. Extensive longitudinal interfaces between monomers have polar and hydrophobic components. At the lateral contacts, a nucleotide-sensitive helix interacts with a loop that contributes to the binding site of taxol in beta-tubulin. PMID- 9989500 TI - Backbone mutations in transmembrane domains of a ligand-gated ion channel: implications for the mechanism of gating. AB - An approach to identify backbone conformational changes underlying nicotinic acetylcholine receptor (nAChR) gating was developed. Specific backbone peptide bonds were replaced with an ester, which disrupts backbone hydrogen bonds at the site of mutation. At a conserved proline residue (alphaPro221) in the first transmembrane (M1) domain, the amide-to-ester mutation provides receptors with near-normal sensitivity, although the natural amino acids tested other than Pro produce receptors that gate with a much larger EC50 than normal. Therefore, a backbone hydrogen bond at this site may interfere with normal gating. In the alphaM2 domain, the amide-to-ester mutation yielded functional receptors at 15 positions, 3 of which provided receptors with >10-fold lower EC50 than wild type. These results support a model for gating that includes significant changes of backbone conformation within the M2 domain. PMID- 9989501 TI - The structure of the protein phosphatase 2A PR65/A subunit reveals the conformation of its 15 tandemly repeated HEAT motifs. AB - The PR65/A subunit of protein phosphatase 2A serves as a scaffolding molecule to coordinate the assembly of the catalytic subunit and a variable regulatory B subunit, generating functionally diverse heterotrimers. Mutations of the beta isoform of PR65 are associated with lung and colon tumors. The crystal structure of the PR65/Aalpha subunit, at 2.3 A resolution, reveals the conformation of its 15 tandemly repeated HEAT sequences, degenerate motifs of approximately 39 amino acids present in a variety of proteins, including huntingtin and importin beta. Individual motifs are composed of a pair of antiparallel alpha helices that assemble in a mainly linear, repetitive fashion to form an elongated molecule characterized by a double layer of alpha helices. Left-handed rotations at three interrepeat interfaces generate a novel left-hand superhelical conformation. The protein interaction interface is formed from the intrarepeat turns that are aligned to form a continuous ridge. PMID- 9989502 TI - Mvwf, a dominant modifier of murine von Willebrand factor, results from altered lineage-specific expression of a glycosyltransferase. AB - We have identified altered lineage-specific expression of an N acetylgalactosaminyltransferase gene, Galgt2, as the gain-of-function mechanism responsible for the action of the Mvwf locus, a major modifier of plasma von Willebrand factor (VWF) level in RIIIS/J mice. A switch of Galgt2 gene expression from intestinal epithelial cell-specific to a pattern restricted to the vascular endothelial cell bed leads to aberrant posttranslational modification and rapid clearance of VWF from plasma. Transgenic expression of Galgt2 directed to vascular endothelial cells reproduces the low VWF phenotype, confirming this switch in lineage-specific gene expression as the likely molecular mechanism for Mvwf. These findings identify alterations in glycosyltransferase function as a potential general mechanism for the genetic modification of plasma protein levels. PMID- 9989503 TI - Functional association of Nmi with Stat5 and Stat1 in IL-2- and IFNgamma-mediated signaling. AB - Using the coiled-coil region of Stat5b as the bait in a yeast two-hybrid screen, we identified the association of Nmi, a protein of unknown function previously reported as an N-Myc interactor. We further show that Nmi interacts with all STATs except Stat2. We evaluated two cytokine systems, IL-2 and IFNgamma, and demonstrate that Nmi augments STAT-mediated transcription in response to these cytokines. Interestingly, Nmi lacks an intrinsic transcriptional activation domain; instead, Nmi enhances the association of CBP/p300 coactivator proteins with Stat1 and Stat5, and together with CBP/p300 can augment IL-2- and IFNgamma dependent transcription. Therefore, our data not only reveal that Nmi can potentiate STAT-dependent transcription, but also suggest that it can augment coactivator protein recruitment to at least some members of a group of sequence specific transcription factors. PMID- 9989504 TI - Structure of CheA, a signal-transducing histidine kinase. AB - Histidine kinases allow bacteria, plants, and fungi to sense and respond to their environment. The 2.6 A resolution crystal structure of Thermotoga maritima CheA (290-671) histidine kinase reveals a dimer where the functions of dimerization, ATP binding, and regulation are segregated into domains. The kinase domain is unlike Ser/Thr/Tyr kinases but resembles two ATPases, Gyrase B and Hsp90. Structural analogies within this superfamily suggest that the P1 domain of CheA provides the nucleophilic histidine and activating glutamate for phosphotransfer. The regulatory domain, which binds the homologous receptor-coupling protein CheW, topologically resembles two SH3 domains and provides different protein recognition surfaces at each end. The dimerization domain forms a central four helix bundle about which the kinase and regulatory domains pivot on conserved hinges to modulate transphosphorylation. Different subunit conformations suggest that relative domain motions link receptor response to kinase activity. PMID- 9989505 TI - Menin interacts with the AP1 transcription factor JunD and represses JunD activated transcription. AB - MEN1 is a tumor suppressor gene that encodes a 610 amino acid nuclear protein (menin) of previously unknown function. Using a yeast two-hybrid screen with menin as the bait, we have identified the transcription factor JunD as a direct menin-interacting partner. Menin did not interact directly with other Jun and Fos family members. The menin-JunD interaction was confirmed in vitro and in vivo. Menin repressed transcriptional activation mediated by JunD fused to the Gal4 DNA binding domain from a Gal4 responsive reporter, or by JunD from an AP1-responsive reporter. Several naturally occurring and clustered MEN1 missense mutations disrupted menin interaction with JunD. These observations suggest that menin's tumor suppressor function involves direct binding to JunD and inhibition of JunD activated transcription. PMID- 9989506 TI - Trading places on DNA--a three-point switch underlies primer handoff from primase to the replicative DNA polymerase. AB - This study reports a primase-to-polymerase switch in E. coli that closely links primase action with extension by DNA polymerase III holoenzyme. We find that primase tightly grips its RNA primer, protecting it from the action of other proteins. However, primase must be displaced before the beta sliding clamp can be assembled on the primed site. A single subunit of the holoenzyme, chi, is dedicated to this primase displacement task. The displacement mechanism depends on a third protein, SSB. Primase requires contact to SSB for its grip on the primed site. The chi subunit also binds SSB, upon which the primase-to-SSB contact is destabilized leading to dissociation of primase and assembly of beta onto the RNA primer. The conservation of this three-point switch, in which two proteins exchange places on DNA via mutually exclusive interaction with a third protein, is discussed. PMID- 9989507 TI - The science and art of radiation oncology after a century. PMID- 9989508 TI - Research recommendations for radiation therapy in older cancer patients. Report from the National Institute on Aging, National Cancer Institute, and American College of Radiology Workshop: radiation therapy and cancer in older persons. PMID- 9989509 TI - Editorial comment on "the link between local recurrence and distant metastasis in human breast cancer" by Serge Koscielny and Maurice Tubiana. PMID- 9989510 TI - The link between local recurrence and distant metastases in human breast cancer. AB - PURPOSE: To distinguish between two possible explanations for the increased incidence of distant metastases observed in patients with locoregional recurrences (LR). Either LR is the signature of tumor aggressiveness, and avoiding recurrences (i.e., by radiotherapy) is of little value. The alternative is that LR is a nidus for metastatic dissemination. METHODS AND MATERIALS: Four thousand patients consecutively treated in the same institution from 1954 to 1975 were studied. None of them had received adjuvant chemotherapy. Tumor characteristics, local recurrence, and distant metastases had been prospectively registered. Duration of metastatic growth and probability of metastatic dissemination were estimated in the subsets of patients. RESULTS: The proportion of metastasis-free patients was reduced by about 80% in all subsets of patients with LR. In patients without LR, the monthly rate of distant metastases incidence decreases continuously with time after initial treatment. Conversely, in patients with local recurrence, this rate increases during the first year at initial treatment and the metastases in excess appear slightly later than in patients without local recurrence. Using a mathematical model, it can be shown that, in patients with local recurrence, nearly all of the metastases in excess had been initiated after initial treatment. The data also suggest that each year a small proportion of grade 1 residual tumors progresses toward a more malignant histologic type. CONCLUSIONS: Our results are not consistent with the hypothesis that a greater tumor aggressiveness in patients with LR could explain the excess of metastases. This conclusion is supported by the analysis of the delays between metastases' emergence, and death, which shows that tumors with or without LR have similar biological characteristics. PMID- 9989511 TI - Local recurrences and distant metastases after breast-conserving surgery and radiation therapy for early breast cancer. AB - PURPOSE: To identify predicting factors for local failure and increased risk of distant metastases by statistical analysis of the data after breast-conserving treatment for early breast cancer. METHODS AND MATERIALS: Between January 1976 and December 1993, 528 patients with nonmetastatic T1 (tumors < or = 1 cm [n = 197], >1 cm [n = 220]) or T2 (tumors < or = 3 cm [n = 111]) carcinoma of the breast underwent wide excision (n = 435) or quadrantectomy (n = 93) with axillary dissection (negative nodal status [n-]: 396; 1-3 involved nodes: 100; >3 involved nodes: 32). Radiotherapy consisted of 45 Gy to the entire breast via tangential fields. Patients with positive axillary lymph nodes received 45 Gy to the axillary and supraclavicular area. Patients with positive axillary nodes and/or inner or central tumor locations received 50 Gy to the internal mammary lymph node area. A boost dose was delivered to the primary site by iridium 192 Implant in 298 patients (mean total dose: 15.2+/-0.07 Gy, range: 15-25 Gy) or by electrons in 225 patients (mean total dose: 14.8+/-0.09 Gy, range: 5-20 Gy). The mean age was 52.5+/-0.5 years (range: 26-86 years) and 267 patient were postmenopausal. Histologic types were as follows: 463 infiltrating ductal carcinomas, 39 infiltrating lobular carcinomas, and 26 other histotypes. Grade distribution according to the Scarff, Bloom, and Richardson (SBR) classification was as follows: 149 grade 1, 271 grade 2, 73 grade 3, and 35 nonclassified. The mean tumor size was 1.6+/-0.3 cm (range: 0.3-3 cm). The intraductal component of the primary tumor was extensive (EIC = IC > or = 25%) in 39 patients. Tumors were microscopically bifocal in 33 cases. Margins were assessed in the majority of cases by inking of the resection margins and were classified as positive in 13 cases, close (< or = 2 mm) in 21, negative (>2 mm tumor-free margin) in 417, and indeterminate in 77. Peritumoral vascular invasion was observed in 40 patients. Tamoxifen was administered for at least 2 years in 176 patients. At least six cycles of adjuvant systemic chemotherapy were administered in 116 patients. The mean follow-up period from the beginning of the treatment was 84.5+/-1.7 months. RESULTS: First events included 44 isolated local recurrences, 8 isolated axillary node recurrences, 44 isolated distant metastases, 1 local recurrence with synchronous axillary node recurrence, 7 local recurrences with synchronous metastases, and 2 local recurrences with synchronous axillary node recurrences and distant metastases. Of 39 pathologically evaluable local recurrences, 33 were classified as true local recurrences and 6 as ipsilateral new primary carcinomas. Seventy patients died (47 of breast carcinoma, 4 of other neoplastic diseases, 10 of other diseases and 9 of unknown causes). The 5- and 10-year rates were, respectively: specific survival 93% and 86%, disease-free survival 85% and 75%, distant metastasis 8.5% and 14%, and local recurrence 7% and 14%. Mean intervals from the beginning of treatment for local recurrence or distant metastases were, respectively, 60+/-6 months (median: 47 months, range: 6-217 months) and 49.5+/ 5.4 months (median: 33 months, range: 6-217 months). After local recurrence, salvage mastectomy was performed in 46 patients (85%) and systemic hormonal therapy and/or chemotherapy was administered to 43 patients. The 5-year specific survival rate after treatment for local recurrence was 78+/-8.2%. Multivariate analysis (multivariate generalization of the proportional hazards model) showed that the probability of local control was decreased by the following four independent factors: young age (< or = 40 yr vs. >40 yr; relative risk [RR]: 3.15, 95% confidence interval [CI]: 1.7-5.8, p = 0.0002), premenopausal status (pre vs. post; RR: 2.9, 95% CI: 1.4-6, p = 0.0048), bifocality (uni- vs. bifocal; RR: 2.7, 95% CI: 2.6-2.8,p = 0.018), and extensive intraductal component (IC <25% vs. IC > or = 25%; RR: 2.6, 95% CI: 13-5.2, p = 0 PMID- 9989512 TI - The influence of age on the delivery, tolerance, and efficacy of thoracic irradiation in the combined modality treatment of limited stage small cell lung cancer. AB - PURPOSE: To assess the impact of age on the delivery, tolerance, and efficacy of thoracic irradiation (TI) for limited small cell lung cancer (L-SCLC). METHODS AND MATERIALS: This is a retrospective review of data from 608 patients 80 years or less with L-SCLC, who participated in two previously reported randomized trials (BR3 and BR.6) of the National Cancer Institute of Canada. All patients received the same chemotherapy, consisting of cyclophosphamide, doxorubicin, vincristine (CAV), and etoposide cisplatin (EP) delivered either in sequential or alternating sequence. In BR.3, TI was given after chemotherapy with randomization to 25 Gy in 10 fractions or 37.5 Gy in 15 fractions. In BR.6, TI (40 Gy in 15 fractions) was given concurrently with EP with randomization to either the early (with cycle 2, week 4) or late (with cycle 6, week 16) arm. RESULTS: A total of 665 patients entered these two trials. Of these, 608 patients were eligible for analysis, 300 in BR.3 and 308 in BR.6. Five hundred and twenty patients were under age 70 and 88 patients were 70 years or older. Baseline characteristics between the two groups were comparable. In BR3, 179 patients (60%) participated in radiotherapy randomization (61% young, 52% elderly), and 176 patients actually received TI. In BR.6, randomization occurred at study entry for all patients, and 282 (91.6%) patients received TI (92% young, 88% elderly). More patients of both age groups randomized to receive late TI did not receive TI (13% and 14%) than those randomized to the early TI arm (3%) of BR.6. We could identify no tendency to reduce field sizes to minimize toxicity in either age group at higher doses of TI. Once TI was started, there was no difference between the two age groups with regards to the proportion of patients who completed TI, although elderly patients were less likely to complete high dose TI. Of those who completed TI, there was no difference in the time to complete TI, mean dose delivered or in the incidence of acute and late TI-related toxicities. No statistical difference in response rate, local relapse rate, or overall survival was seen between young and older age groups. CONCLUSION: In summary, in the dose range examined, age does not appear to impact on the delivery, tolerance or efficacy of TI in the combined modality management of L-SCLC. Potentially curative combined modality treatment should not be withheld on the basis of age. PMID- 9989513 TI - Pion conformal radiation of prostate cancer: results of a randomized study. AB - PURPOSE: To compare the efficacy of pion radiation therapy with conventional external beam photon therapy, for the treatment of locally advanced stage T3/4, N0, M0 adenocarcinoma of the prostate. METHODS AND MATERIALS: Two hundred seventeen eligible patients were randomly allocated to either photon or pion therapy. No adjuvant hormone therapy was used. RESULTS: Median follow-up was 42 months (range 2-90). Acute bladder toxicity was worse in the pion arm, p = 0.2, but other acute toxicity did not differ. Late grade 2 toxicity was significantly less in the pion arm (29% at 5 years versus 48%, p = 0.002), but late grade 3 or 4 toxicity did not differ. Clinical local control was not significantly different between treatment arms (64% after 5 years with photons, 56% with pions, p = 0.6). Cause-specific and overall survival also did not differ (p = 0.7). There was a significant delay in time to first failure in the photon arm, largely as a result of decreased biochemical relapse, p = 0.01. A multivariate analysis is presented. CONCLUSION: Pion therapy was well tolerated, with increased acute toxicity and significantly decreased late tissue injury. This contrasts with the late toxicity observed with higher LET particle therapy such as neutron therapy. No improvement in local control with pion therapy was observed. PMID- 9989514 TI - Definition of the prostate in CT and MRI: a multi-observer study. AB - PURPOSE: To determine, in three-dimensions, the difference between prostate delineation in magnetic resonance (MR) and computer tomography (CT) images for radiotherapy treatment planning. PATIENTS AND METHODS: Three radiation oncologists, considered experts in the field, outlined the prostate without seminal vesicles both on CT, and axial, coronal, and sagittal MR images for 18 patients. To compare the resulting delineated prostates, the CT and MR scans were matched in three-dimensions using chamfer matching on bony structures. The volumes were measured and the interscan and interobserver variation was determined. The spatial difference between delineation in CT and MR (interscan variation) as well as the interobserver variation were quantified and mapped three-dimensionally (3D) using polar coordinates. A urethrogram was performed and the location of the tip of the dye column was compared with the apex delineated in CT and MR images. RESULTS: Interscan variation: CT volumes were larger than the axial MR volumes in 52 of 54 delineations. The average ratio between the CT and MR volumes was 1.4 (standard error of mean, SE: 0.04) which was significantly different from 1 (p < 0.005). Only small differences were observed between the volumes outlined in the various MR scans, although the coronal MR volumes were smallest. The CT derived prostate was 8 mm (standard deviation, SD: 6 mm) larger at the base of the seminal vesicles and 6 mm (SD 4 mm) larger at the apex of the prostate than the axial MRI. Similar figures were obtained for the CT and the other MRI scans. Interobserver variation: The average ratio between the volume derived by one observer for a particular scan and patient and the average volume was 0.95, 0.97, and 1.08 (SE 0.01) for the three observers, respectively. The 3D pattern of the overall observer variation (1 SD) for CT and axial MRI was similar and equal to 3.5 to 2.8 mm at the base of the seminal vesicles and 3 mm at the apex. CONCLUSION: CT-derived prostate volumes are larger than MR derived volumes, especially toward the seminal vesicles and the apex of the prostate. This interscan variation was found to be larger than the interobserver variation. Using MRI for delineation of the prostate reduces the amount of irradiated rectal wall, and could reduce rectal and urological complications. PMID- 9989515 TI - Prostate seed implant quality assessment using MR and CT image fusion. AB - PURPOSE: After a seed implant of the prostate, computerized tomography (CT) is ideal for determining seed distribution but soft tissue anatomy is frequently not well visualized. Magnetic resonance (MR) images soft tissue anatomy well but seed visualization is problematic. We describe a method of fusing CT and MR images to exploit the advantages of both of these modalities when assessing the quality of a prostate seed implant. METHODS AND MATERIALS: Eleven consecutive prostate seed implant patients were imaged with axial MR and CT scans. MR and CT images were fused in three dimensions using the Pinnacle 3.0 version of the ADAC treatment planning system. The urethra and bladder base were used to "line up" MR and CT image sets during image fusion. Alignment was accomplished using translation and rotation in the three ortho-normal planes. Accuracy of image fusion was evaluated by calculating the maximum deviation in millimeters between the center of the urethra on axial MR versus CT images. Implant quality was determined by comparing dosimetric results to previously set parameters. RESULTS: Image fusion was performed with a high degree of accuracy. When lining up the urethra and base of bladder, the maximum difference in axial position of the urethra between MR and CT averaged 2.5 mm (range 1.3-4.0 mm, SD 0.9 mm). By projecting CT-derived dose distributions over MR images of soft tissue structures, qualitative and quantitative evaluation of implant quality is straightforward. CONCLUSIONS: The image-fusion process we describe provides a sophisticated way of assessing the quality of a prostate seed implant. Commercial software makes the process time efficient and available to any clinical practice with a high-quality treatment planning system. While we use MR to image soft tissue structures, the process could be used with any imaging modality that is able to visualize the prostatic urethra (e.g., ultrasound). PMID- 9989516 TI - Prospective evaluation of the effect of ionizing radiation on the bladder tumor associated (BTA) urine test. AB - PURPOSE: To prospectively evaluate the effect of ionizing radiation on the results of the bladder tumor-associated antigen (BTA) test. By examining this question, we sought to determine its potential use as a monitoring test for the detection of recurrent transitional carcinoma of the bladder in patients who have received prior radiotherapy for bladder preservation. MATERIALS AND METHODS: Between February 1996 and April 1997, 18 patients with nonbladder pelvic malignancies and no history of bladder cancer, received irradiation to the bladder. These patients were prospectively evaluated using the BTA test at the end of the external-beam radiation (EBRT) and at 3-month follow-up intervals. Urine cytology was analyzed in 16 of the 18 patients at the end of EBRT. A median of 3 separate measurements were made (range 1-6) on each patient. The median dose of EBRT was 50.4 Gy (range 30-68 Gy). Seven patients underwent brachytherapy as part of their treatment course. BTA results and time intervals were recorded and analyzed using univariate and Kaplan-Meyer methodologies. RESULTS: A total of 10 (56%) of the 18 patients had a positive BTA test at some time following completion of EBRT. Of the 10 positive tests, 9 returned to negative in a median of 42 weeks from completion of EBRT. Treatment with chemotherapy, brachytherapy, calculated bladder dose, and total external beam dose did not significantly influence either the number of positive tests or the time to resolution of the positive test in this small group of patients. All screened urine samples were negative for malignant cells and 11 (69%) of 16 showed changes consistent with ionizing radiation. CONCLUSION: Our findings support the hypothesis that ionizing radiation can cause transient positive results in the BTA test, but that these normalize with time. Although it requires further testing, it seems that the BTA test may be useful in the detection of recurrence in patients with bladder cancer who have been treated with definitive irradiation for bladder preservation. PMID- 9989517 TI - Patterns of failure following high-dose 3-D conformal radiotherapy for high-grade astrocytomas: a quantitative dosimetric study. AB - PURPOSE: To analyze the failure patterns for patients with high-grade astrocytomas treated with high-dose conformal radiotherapy (CRT) using a quantitative technique to calculate the dose received by the CT- or MR-defined recurrence volume and to assess whether the final target volume margin used in the present dose escalation study requires redefinition before further escalation. METHODS AND MATERIALS: Between 4/89 and 10/95, 71 patients with high grade supratentorial astrocytomas were entered in a phase I/II dose escalation study using 3-D treatment planning and conformal radiotherapy. All patients were treated to either 70 or 80 Gy in conventional daily fractions of 1.8-2.0 Gy. The clinical and planning target volumes (CTV, PTV) consisted of successively smaller volumes with the final PTV defined as the enhancing lesion plus 0.5 cm margin. As of 10/95, 47 patients have CT or MR evidence of disease recurrence/progression. Of the 47 patients, 36 scans obtained at the time of recurrence were entered into the 3-D radiation therapy treatment planning system. After definition of the recurrent tumor volumes, the recurrence scan dataset was registered with the pretreatment CT dataset so that the actual dose received by the recurrent tumor volumes during treatment could be accurately calculated and then analyzed dosimetrically using dose-volume histograms. Recurrences were divided into several categories: 1) "central," in which 95% or more of the recurrent tumor volume (Vrecur) was within D95, the region treated to high dose (95% of the prescription dose); 2) "in-field," in which 80% or more of Vrecur was within the D95 isodose surface; 3) "marginal," when between 20 and 80% of Vrecur was inside the D95 surface; 4) "outside," in which less than 20% of Vrecur was inside the D95 surface. RESULTS: In 29 of 36 patients, a solitary lesion was seen on recurrence scans. Of the 29 solitary recurrences, 26 were central, 3 were marginal, and none were outside. Multiple recurrent lesions were seen in seven patients: three patients had multiple central and/or in-field lesions only, three patients had central and/or in-field lesions with additional small marginal or outside lesions, and one patent had 6 outside and one central lesion. Since total recurrence volume was used in the final analysis, 6 of the 7 patients with multiple recurrent lesions were classified into centra/in-field category. CONCLUSION: Analysis of the 36 evaluable patients has shown that 32 of 36 patients (89%) failed with central or in-field recurrences, 3/36 (8%) had a significant marginal component to the recurrence, whereas only 1/36 (3%) could be clearly labeled as failing mainly outside the high-dose region. Seven patients had multiple recurrences, but only 1 of 7 had large-volume recurrences outside the high-dose region. This study shows that the great majority of patient recurrences that occur after high-dose (70 or 80 Gy) conformal irradiation are centrally located: only 1/36 patients (with 7 recurrent lesions) had more than 50% of the recurrence volume outside the region previously treated to high dose. Further dose escalation to 90 Gy (and beyond) thus seems reasonable, based on the same target volume definition criteria PMID- 9989518 TI - Accelerated regression of brain metastases in patients receiving whole brain radiation and the topoisomerase II inhibitor, lucanthone. AB - PURPOSE: To determine if lucanthone crossed the blood-brain barrier in experimental animals; and to determine accelerated tumor regression of human brain metastases treated jointly with lucanthone and whole brain radiation. METHODS AND MATERIALS: The organ distribution of 3H lucanthone in mice and 125I lucanthone in rats was determined to learn if lucanthone crossed the blood-brain barrier. Size determinations were made of patients' brain metastases from magnetic resonance images or by computed tomography before and after treatment with 30 Gy whole brain radiation alone or with lucanthone. RESULTS: The time course of lucanthone's distribution in brain was identical to that in muscle and heart after intraperitoneal or intravenous administration in experimental animals. Lucanthone, therefore, readily crossed the blood-brain barrier in experimental animals. CONCLUSION: Compared with radiation alone, the tumor regression in patients with brain metastases treated with lucanthone and radiation was accelerated, approaching significance using a permutation test at p = 0.0536. PMID- 9989519 TI - Pulsed low dose rate brachytherapy for uterine cervix carcinoma. AB - PURPOSE: To analyze the outcome and complication rates for patients treated with curative-intent pulsed low dose rate (PLDR) brachytherapy and external beam radiation therapy (EBRT) for uterine cervical carcinoma. METHODS AND MATERIALS: Fifty-two patients have been treated, of whom 6 were excluded from analysis due to limited follow-up. Six patients were stage Ib, 3 were IIa, 11 IIb, 3 IIIa, 14 IIIb, 1 IVa, and 9 were treated for local recurrences following primary surgery for stage Ib disease. Thirty-six patients had squamous cell carcinoma, 8 adenocarcinoma, 1 adenosquamous, and 1 carcinosarcoma. Thirty-one had a staging laparotomy prior to radiation therapy. Brachytherapy was interstitial in 18 patients, and intracavity in 28. The median EBRT central pelvis dose was 45 Gy in 25 fractions. Median total prescribed doses (EBRT plus PLDR) were 75.8 Gy to the implant volume with interstitial, and 84.1 Gy to the A points with intracavitary, at a median dose rate of 0.55 Gy per pulse per hour. Six patients had laparotomy documented periaortic node involvement, and received EBRT to this site, 45 Gy in 25 fractions. Thirty patients received concomitant weekly cisplatin chemotherapy (40 mg/m2). RESULTS: With a median follow-up of 25 months (range 6 to 55 months) actuarial 4-year disease-free survival (DFS) rates are 66% for the entire group: stage Ib 100%, stage II 69%, stage III/IVa 68%, and 43% in patients treated for recurrences after surgery for initial stage Ib disease. Pelvic nodes contained tumor in 13 of the 31 patients (41.9%) who underwent laparotomy, as did periaortic nodes in 6 (19.4%). Patients with negative pelvic nodes had a 4-year actuarial DFS of 75% versus 59% with positive pelvic (and negative periaortic) nodes, and 50% with positive periaortic nodes. Using the RTOG late radiation morbidity scoring criteria, there were no grade V complications. Grade IV complications occurred in 2 patients (4.3%). One was a rectovaginal fistula and the other a vesicovaginal fistula, each occurring subsequent to a biopsy revealing benign tissue. One patient (2.2%) had a grade III complication (frequent hematuria), and 5 (10.9%) had grade II complications. CONCLUSIONS: PLDR brachytherapy is a safe and effective brachytherapy method in the treatment of cervix carcinoma. It combines the physics benefits of dose optimization and the radiobiologic advantages of low dose rate brachytherapy. It eliminates radiation exposure to staff and visitors as well as the need for a source inventory. Although further follow-up will be required, it appears to provide outcome which compares favorably to other methods of brachytherapy delivery, and results in a low rate of complications. PMID- 9989520 TI - Clinical radiobiology of glottic T1 squamous cell carcinoma. AB - PURPOSE: Radiation therapy is the treatment of choice for early glottic squamous cell cancer in many institutions over the world. Despite a relatively homogenous clinical model of T1 glottic tumors for the fractionation studies, the relationships between dose-time parameters remain unclear. To analyze the influence of fractionation parameters and hemoglobin level on tumor cure, this study has been performed. MATERIALS AND METHODS: This is a retrospective review of 235 patients with T1N0M0 glottic cancer treated by radiation therapy alone given in a conventional schedule with 5 fractions each week. The individual total dose, dose per fraction, and overall treatment time (OTT) ranged from 51-70 Gy, 1.5-3.0 Gy, and 24-79 days, respectively. The median follow-up was 48 months. Patient data--total dose, dose per fraction, OTT, and hemoglobin level (Hb) measured before the radiation treatment--were fitted by the mixed LQ/log-logistic model. RESULTS: The 5-year local relapse-free survival rate was 84%. All parameters included in the mixed LQ/log-logistic model improved the fit significantly. The dose-response curve for 235 patients with T1 glottic cancer was well defined and steep, and showed significant decrease in tumor control probability (TCP) when total doses were below 61 Gy. The 10-day prolongation of OTT, from 45 to 55 days, decreased the TCP by 13%. The dose of 0.35 Gy/day, compensated repopulation during the 1 day of prolongation, which indicates a potential doubling time (Tpot) for glottic T1 tumor clonogens of 5.5 days. The drop of Hb level of 1 g/dl (from 13.8 g/dl to 12.8 g/dl) gave a 6% decrease of TCP, provided that OTT was 45 days. CONCLUSION: The significant correlation between the total dose, overall treatment time, hemoglobin concentration, and tumor control probability has been found for T1 glottic cancer. PMID- 9989521 TI - Concurrent twice-a-week docetaxel and radiotherapy: a dose escalation trial with immunological toxicity evaluation. AB - PURPOSE: In vitro studies show that docetaxel (Taxotere) is potent radiosensitizer. In a previous study we observed a 27% complete response rate after radiotherapy and weekly docetaxel for non-small-cell lung cancer. In this dose escalation study we investigated the feasibility of a twice-a-week docetaxel regimen together with conventionally fractionated radiotherapy for brain, chest, and pelvic tumors. METHODS AND MATERIALS: Nine patients with stage IIIb lung cancer, 9 with stage IVa pelvic tumors, and 9 with brain glioblastoma were recruited. The starting dose was 15 mg/m2 (twice a week) and was escalated by 4 mg/m2 increments every 3 patients with chest, pelvic, and brain tumors. RESULTS: The maximum tolerated dose of docetaxel was 15 mg/m2 (twice a week) for chest and pelvic cancer patients. The dose-limiting toxicity (DLT) was asthenia and mucosal toxicity (esophagitis or diarrhea in chest and pelvic tumors, respectively). Patients with glioblastomas received 23 mg/m2 (twice a week) without toxicity. Complete response of the chest disease was observed in 3/9 (33%) patients and partial response in 4/9 (44%). Three patients with glioblastoma had a partial response. In pelvic malignancies a high complete response rate was observed (4/9; 45%). Severe monocytopenia and lymphocytopenia were observed during the fourth week of treatment. IgG and IgA immunoglobulins were also reduced. This coincided with the onset of asthenia and severe mucosal toxicity. Asthenia was absent in patients treated for brain tumors, and lymphocyte toxicity was less pronounced. CONCLUSIONS: Docetaxel radiochemotherapy is a promising therapeutic approach for locally advanced cancer. The recommended dose of docetaxel for chest and pelvic cancer patients is 15 mg/m2 twice a week. Patients with brain tumors can be safely treated with higher doses of docetaxel (23 mg/m2 twice a week) without toxicity. The severe immunologic toxicity observed suggests that granulocyte macrophage colony-stimulating factor (GM-CSF) and immunoglobulin administration may be important in the efficacy and tolerance of taxane-based radiochemotherapy. Randomized trials are required to assess whether the efficacy of docetaxel radiochemotherapy depends on the frequency of docetaxel administration during radiation treatment. PMID- 9989522 TI - A real-time audit of radiation therapy in a regional cancer center. AB - PURPOSE: To report the development, structure, and implementation of a real-time clinical radiotherapy audit of the practice of radiation oncology in a regional cancer center. METHODS AND MATERIALS: Radiotherapy treatment plans were audited by a real-time peer-review process over an 8-year period (1989-1996). The overall goal of the audit was to establish a process for quality assurance (QA) of radiotherapy planning and prescription for individual patients. A parallel process was developed to audit the implementation of intervention-specific radiotherapy treatment policies. RESULTS: A total of 3052 treatment plans were audited. Of these, 124 (4.1%) were not approved by the audit due to apparent errors in radiation planning. The majority of the nonapproved plans (79%) were modified prior to initiating treatment; the audit provided important clinical feedback about individual patient care in these instances. Most of the remaining nonapproved plans were deviations from normal practice due to patient-specific considerations. A further 110 (3.6% of all audited plans) were not approved by the audit due to deviations from radiotherapy treatment policy. A minority of these plans (22%) were modified prior to initiating treatment and the remainder provided important feedback for continuous quality improvement of treatment policies. CONCLUSION: A real-time audit of radiotherapy practice in a regional cancer center setting proved feasible and provided important direct and indirect patient benefits. PMID- 9989523 TI - ACR appropriateness criteria. Expert Panel on Radiation Oncology. American College of Radiology. PMID- 9989524 TI - Intratracheal injection of adenovirus containing the human MnSOD transgene protects athymic nude mice from irradiation-induced organizing alveolitis. AB - PURPOSE: A dose and volume limiting factor in radiation treatment of thoracic cancer is the development of fibrosis in normal lung. The goal of the present study was to determine whether expression prior to irradiation of a transgene for human manganese superoxide dismutase (MnSOD) or human copper/zinc superoxide dismutase (Cu/ZnSOD) protects against irradiation-induced lung damage in mice. METHODS AND MATERIALS: Athymic Nude (Nu/J) mice were intratracheally injected with 10(9) plaque-forming units (PFU) of a replication-incompetent mutant adenovirus construct containing the gene for either human MnSOD, human copper/zinc superoxide dismutase (Cu/ZnSOD) or LacZ. Four days later the mice were irradiated to the pulmonary cavity to doses of 850, 900, or 950 cGy. To demonstrate adenoviral infection, nested reverse transcriptase-polymerase chain reaction (RT-PCR) was carried out with primers specific for either human MnSOD or Cu/ZnSOD transgene on freshly explanted lung, trachea, or alveolar type II cells, and immunohistochemistry was used to measure LacZ expression. RNA was extracted on day 0, 1, 4, or 7 after 850 cGy of irradiation from lungs of mice that had previously received adenovirus or had no treatment. Slot blot analysis was performed to quantitate RNA expression for IL-1, tumor necrosis factor (TNF) alpha, TGF-beta, MnSOD, or Cu/ZnSOD. Lung tissue was explanted and tested for biochemical activity of MnSOD or Cu/ZnSOD after adenovirus injection. Other mice were sacrificed 132 days after irradiation, lungs excised, frozen in OCT, (polyvinyl alcohol, polyethylene glycol mixture) sectioned, H&E stained, and evaluated for percent of the lung demonstrating organizing alveolitis. RESULTS: Mice injected intratracheally with adenovirus containing the gene for human MnSOD had significantly reduced chronic lung irradiation damage following 950 cGy, compared to control mice or mice injected with adenovirus containing the gene for human Cu/ZnSOD or LacZ. Immunohistochemistry for LacZ protein in adenovirus LacZ (Ad-LacZ)-injected mice demonstrated expression of LacZ in both the upper and lower airway. Nested RT-PCR showed lung expression of MnSOD and Cu/ZnSOD for at least 11 days following infection with each respective adenovirus construct. Nested RT-PCR using primers specific for human MnSOD demonstrated increased expression of the human MnSOD transgene in the trachea and alveolar type II cells 4 days after virus injection on the day of irradiation. At this time point, increased biochemical activity of MnSOD and Cu/ZnSOD respectively, was detected in lungs from these two adenovirus groups, compared to each other or to control or adenovirus LacZ mice. Slot blot analysis of RNA from lungs of mice in each group following 850 cGy irradiation demonstrated decreased expression of mRNA for interleukin-I (IL-1), TNF-alpha, and transforming growth factor-beta (TGF-beta) in the MnSOD adenovirus-injected mice, compared to irradiated control, LacZ, or Cu/ZnSOD adenovirus-injected, irradiated mice. Mice receiving adenovirus MnSOD showed decreased organizing alveolitis at 132 days in all three dose groups, compared to irradiated control or Ad-LacZ, or Ad-Cu/ZnSOD mice. CONCLUSIONS: Overexpression of MnSOD in the lungs of mice prior to irradiation prevents irradiation-induced acute and chronic damage quantitated as decreased levels of mRNA for IL-1, TNF-alpha, and TGF-beta in the days immediately following irradiation, and decrease in the percent of lung demonstrating fibrosis or organizing alveolitis at 132 days. These data provide a rational basis for development of gene therapy as a method of protection of the normal lung from acute and chronic sequelae of ionizing irradiation. PMID- 9989525 TI - A novel technique, using radioluminography, for the measurement of uniformity of radiolabelled antibody distribution in a colorectal cancer xenograft model. AB - PURPOSE: Radioimmunotherapy of cancer employs an antitumour antibody to carry a radionuclide selectively to deposits of cancer. Conventional dose estimates, based on the Medical Internal Radiation Dose (MIRD) formulation, assume uniform distribution of radiolabelled antitumour antibody within tissue source regions. This assumption has been tested by using a statistical model to predict the pixel value distribution obtained from the digitised radioluminographs of a known radioactive source. The model uses the statistical nature of the detection of radiation where any uniform source distribution can be expected to have a detected histogram of pixel counts that is normal or Gaussian. Therefore, any test for the degree of normality in the detected distribution is also a measure of the degree of uniformity in the source. METHODS AND MATERIALS: Three statistical techniques have been used to test the normality of the histogram of pixel values produced from the antibody distribution in a tissue section. Kurtosis, skew, and Lilliefor's are tests for normality and have statistically defined critical values for a normal distribution. After administration of 125I labelled F(ab)2 antibody to nude mice bearing the LS174T colorectal cancer xenograft, the uniformity of antibody distribution in tumour and healthy tissues is measured using the radioluminographs of formalin-fixed paraffin sections. The test statistic for kurtosis, skew, and Lilliefor's is calculated for each tissue and is compared to critical values from statistical tables. RESULTS: The radiolabelled antibody is distributed uniformly in liver, spleen, muscle, lung, and colon and, therefore, conforms to conventional use of the MIRD formulation. The study showed that the kidney cortex and medulla should be considered separately in macroscopic absorbed-dose calculations, as should bone marrow and hard bone. Antibody heterogeneity in the tumour necessitates the incorporation of a microdosimetric tumour model into a macrodosimetry model for the accurate calculation of absorbed dose in all tissues. PMID- 9989526 TI - DNA double-strand break repair, DNA-PK, and DNA ligases in two human squamous carcinoma cell lines with different radiosensitivity. AB - PURPOSE: Variation in sensitivity to radiotherapy among tumors has been related to the capacity of cells to repair radiation-induced DNA double-strand breaks (DSBs). DNA-dependent protein kinase (DNA-PK) and DNA ligases may affect DNA dsb rejoining. This study was performed to compare rate of rejoining of radiation induced DSBs, DNA-PK, and DNA ligase activities in two human squamous carcinoma cell lines with different sensitivity to ionizing radiation. METHODS AND MATERIALS: Cell survival of two human squamous carcinoma cell lines, UM-SCC-1 and UM-SCC-14A, was determined by an in vitro clonogenic assay. DSB rejoining was studied using pulsed field gel electrophoresis (PFGE). DNA-PK activity was determined using BIOTRAK DNA-PK enzyme assay system (Amersham). DNA ligase activity in crude cell extracts was measured using [5'-33P] Poly (dA) x (oligo (dT) as a substrate. Proteolytic degradation of proteins was analyzed by means of Western blotting. RESULTS: Applying the commonly used linear-quadratic equation to describe cell survival, S = e-alphaD-betaD2, the two cell lines roughly have the same alpha value (approximately 0.40 Gy(-1)) whereas the beta value was considerably higher in UM-SCC-14A (0.067 Gy(-2)+/-0.007 Gy(-2) [SEM]) as compared to UM-SCC-1 (0.013 Gy(-2)+/-0.004 Gy(-2) [SEM]). Furthermore, UM-SCC-1 was more proficient in rejoining of X-ray-induced DSBs as compared to UM-SCC-14A as quantified by PFGE. The constitutive level of DNA-PK activity was 1.6 times higher in UM-SCC-1 as compared to UM-SCC-14A ( < 0.05). The constitutive level of DNA ligase activity was similar in the two cell lines. CONCLUSIONS: The results suggest that the proficiency in rejoining of DSBs is associated with DNA-PK activity but not with total DNA ligase activity. PMID- 9989527 TI - Modeling late effects in hypofractionated stereotactic radiotherapy. AB - PURPOSE: To investigate the effect of increasing fraction size on cell survival in late responding normal tissues. The hypothesis is that total dose can be reduced for constant tumor cell kill and there will be consequent advantage for some surrounding normal tissue cells. Also, the volume of normal tissue that can potentially be damaged by increasing fraction size is minimized by a high degree of dose conformation achievable in stereotactic radiotherapy (SRT). METHODS AND MATERIALS: The linear quadratic (LQ) model has been used to calculate the allowed reduction in total dose with increased fraction size, using tumor alpha/beta ratios of 5 Gy and 10 Gy. Effect on normal tissue is calculated using an alpha/beta ratio of 3 Gy. Maximum dose is normalized to 100% and the effect on normal tissue at different isodose levels assessed. A new quantity, the standard percentage dose, is proposed in order to describe a dose distribution in terms of an isodose distribution for a standard fraction size. Integral biologically effective dose (IBED) in the brainstem is calculated, where the variation with isocenter position and fraction size is considered. RESULTS: The decreasing total dose resulting from increasing the dose per fraction is found to reduce late normal tissue effect for low isodose levels. The threshold isodose level at which there is an advantage corresponds to the ratio of normal tissue to tumor alpha/beta ratios. Brainstem IBED for a higher dose per fraction increases relative to that for a low dose per fraction, when a larger volume of brainstem is covered by high isodose levels. CONCLUSION: Hypofractionation may be biologically sound when a small volume of normal tissue is covered by high isodose levels. There is a calculated advantage in using larger fractions in terms of cell survival at low isodose levels. PMID- 9989528 TI - Setup reproducibility in radiation therapy for lung cancer: a comparison between T-bar and expanded foam immobilization devices. AB - PURPOSE: Physiologic and non-physiologic tumor motion complicates the use of tight margins in three-dimensional (3D) conformal radiotherapy. Setup reproducibility is an important non-physiologic cause of tumor motion. The objective of this study is to evaluate and compare patient setup reproducibility using the reusable T-bar and the disposable expanded foam immobilization device (EFID) in radiation therapy for lung cancer. METHODS AND MATERIALS: Two hundred forty-four portal films were taken from 16 prospectively accrued patients treated for lung cancer. Patients were treated with either a pair of anterior and posterior parallel opposing fields (POF), or a combination of POF and a three field isocentric technique. Each patient was treated in a supine position using either the T-bar setup or EFID. Six patients were treated in both devices over their treatment courses. Field placement analysis was used to evaluate 3D setup reproducibility, by comparing positions of bony landmarks relative to the radiation field edges in digitized simulator and portal images. Anterior posterior, lateral, and longitudinal displacements, as well as field rotations along coronal and sagittal planes were measured. Statistical analyses of variance were applied to the deviations among portal films of all patients and the subgroup treated with both immobilization methods. RESULTS: For the T-bar immobilization device, standard deviations of the setup reproducibility were 5.1, 3.7, and 5.1 mm in the anterior-posterior, lateral, and longitudinal dimensions, respectively. Rotations in the coronal plane and the sagittal plane were 0.9 degrees and 1.0 degrees, respectively. For the EFID, corresponding standard deviations of set up reproducibility were 3.6 mm, 5.3 mm, 5.4 mm, 0.7 degrees and 1.4 degrees, respectively. There was no statistically significant difference (p = 0.22) in the 3D setup reproducibility between T-bar and EFID. Subgroup analysis for the patients who were treated with both immobilization devices did not reveal a difference either. There was no consistent systematic error from simulator to treatment unit identified for either immobilization device. CONCLUSION: Although the optimal immobilization technique and patient positioning for thoracic radiotherapy have yet to be determined, this study indicates that T-bar is comparable with EFID in its setup reproducibility. In view of the inherent advantages of T-bar, it has become a standard immobilization device at our institution. The observed range of displacements in field positioning with either immobilization device implies that one cm (two standard deviations [SD] of setup error) will be a more appropriate margin to allow for setup variability in radiation therapy for lung cancer. PMID- 9989529 TI - Transrectal ultrasound applicator for prostate heating monitored using MRI thermometry. AB - PURPOSE: For potential localized hyperthermia treatment of tumors within the prostate, an ultrasound applicator consisting entirely of nonmagnetic materials for use with magnetic resonance imaging (MRI) has been developed and tested on muscle tissue ex vivo and in vivo. METHODS AND MATERIALS: A partial-cylindrical intracavitary transducer consisting of 16 elements in a 4 x 4 pattern was constructed. It produced a radially propagating acoustic pressure field. Each element of this array (1.5 x 0.75 cm), operating at 1.5 MHz, could be separately powered to produce a desired energy deposition pattern within a target volume. Spatial and temporal temperature elevations were determined using the temperature dependent proton resonant frequency (PRF) shift and phase subtraction of MR images acquired during ultrasonic heating. Four rabbits were exposed to the ultrasound to raise the local tissue temperature to 45 degrees C for 25 minutes. Six experiments compared thermocouple temperature results to PRF shift temperature results. RESULTS: The tests showed that the multi-element ultrasound applicator was MRI-compatible and allowed imaging during sonication. The induced temperature distribution could be controlled by monitoring the RF power to each transducer element. Therapeutic temperature elevations were easily achieved in vivo at power levels that were about 16% of the maximum system power. From the six thermocouple experiments, comparison between the thermocouple temperature and the PRF temperature yielded an average error of 0.34+/-0.36 degrees C. CONCLUSIONS: The MRI-compatible intracavitary applicator and driving system was able to control the ultrasound field and temperature pattern in vivo. MRI thermometry using the PRF shift can provide adequate temperature accuracy and stability for controlling the temperature distribution. PMID- 9989530 TI - Accuracy evaluation of fusion of CT, MR, and spect images using commercially available software packages (SRS PLATO and IFS). AB - PURPOSE: A problem for clinicians is to mentally integrate information from multiple diagnostic sources, such as computed tomography (CT), magnetic resonance (MR), and single photon emission computed tomography (SPECT), whose images give anatomic and metabolic information. METHODS AND MATERIALS: To combine this different imaging procedure information, and to overlay correspondent slices, we used commercially available software packages (SRS PLATO and IFS). The algorithms utilize a fiducial-based coordinate system (or frame) with 3 N-shaped markers, which allows coordinate transformation of a clinical examination data set (9 spots for each transaxial section) to a stereotactic coordinate system. The N shaped markers were filled with fluids visible in each modality (gadolinium for MR, calcium chloride for CT, and 99mTc for SPECT). The frame is relocatable, in the different acquisition modalities, by means of a head holder to which a face mask is fixed so as to immobilize the patient. Position errors due to the algorithms were obtained by evaluating the stereotactic coordinates of five sources detectable in each modality. RESULTS: SPECT and MR position errors due to the algorithms were evaluated with respect to CT: deltax was < or = 0.9 mm for MR and < or = 1.4 mm for SPECT, deltay was < or = 1 mm and < or = 3 mm for MR and SPECT, respectively. Maximal differences in distance between estimated and actual fiducial centers (geometric mismatch) were in the order of the pixel size (0.8 mm for CT, 1.4 mm for MR, and 1.8 mm for SPECT). In an attempt to distinguish necrosis from residual disease, the image fusion protocol was studied in 35 primary or metastatic brain tumor patients. CONCLUSIONS: The image fusion technique has a good degree of accuracy as well as the potential to improve the specificity of tissue identification and the precision of the subsequent treatment planning. PMID- 9989531 TI - Regarding Zelefsky, Leibel, Gaudin, et al., IJROBP 1998;41:491-500. PMID- 9989532 TI - Re: Ogino I, Kitamura T, Okajima H, Matsubara S. High-dose-rate brachytherapy in the management of cervical and vaginal intraepithelial neoplasia Int J Radiat Oncol Biol Phys 1998; 40:881-887. PMID- 9989533 TI - Somatization reconsidered: incorporating the patient's experience of illness. AB - The large and heterogeneous group of patients with "unexplained somatic symptoms," with or without coexisting psychiatric, "functional," or "organic" illnesses, provides continuing difficulty for clinicians. The construct of somatization artificially separates bodily and psychological symptoms that patients experience as a unified whole. Concurrent chronic illnesses make it difficult to exclude "general medical conditions." The diagnosis requires that the patient seek medical care. Conflict between patients' experiences of illness and physicians' diagnostic categories, and fear of blaming the patient, complicate naming and characterizing the illness. We recommend an approach to clinical care that involves exploring the patient's life context, finding mutually meaningful language to arrive at a name for the illness, normalizing the patient's bodily experience of distress, using a chronic disease model that attends to functioning, and addressing the physician's need for certainty and efficacy. Health systems can help coordinate care and avoid iatrogenic harm by appropriately controlling access to medical services. PMID- 9989534 TI - Sympathetic activation in heart failure and its treatment with beta-blockade. AB - Multiple models explaining the pathogenesis of heart failure have been put forth during the past 5 decades. These models were modified as clinical evidence supported or refuted their assumptions. During the past 2 decades, heart failure models emphasized the importance of neurohormonal systems in heart failure progression. The positive impact that angiotensin-converting enzyme inhibitors have had on mortality from heart failure has bolstered the neurohormonal theory. Attention recently has turned to the sympathetic nervous system and its potential deleterious effects on the cardiovascular system in heart failure. The sympathetic nervous system can negatively impact the cardiovascular system in heart failure in several ways, including down-regulating beta1-receptors, exerting direct toxic effects on the myocardium, and contributing to myocardial remodeling and life-threatening arrhythmias. Beta-adrenergic blockers have shown promise for reducing morbidity and mortality in heart failure, but definitive reductions in mortality remain to be shown by future investigations. PMID- 9989535 TI - Emerging noninvasive biochemical measures to predict cardiovascular risk. AB - New predictors of cardiovascular events are needed to improve the accuracy of risk stratification. Such predictors should be easily measurable in the population and potentially modifiable. This review reports on new biomarkers that are closely linked to the pathogenic mechanisms underlying the progression of the atherosclerotic plaque leading to rupture and thrombosis that ultimately precipitate acute clinical events, such as stroke and myocardial infarction. These risk factors have been associated with subclinical or clinical cardiovascular disease in large populations and include markers of lipoprotein and lipid metabolism, vitamin B12 metabolism, fibrinolysis, coagulation, inflammation, infection, endothelial dysfunction, the angiotensin system, and oxidative stress. For other key processes of atherosclerosis and cardiac disease, such as apoptosis or programmed cell death, there are currently no markers that can be measured noninvasively. Atherosclerosis is a multifactorial condition and possibly only a subset of factors are the main determinants of disease in a given patient. A better definition of the cardiovascular risk profile will help to better target primary and secondary prevention. Further epidemiological studies are needed to characterize the actual predictive and clinical value of these new emerging cardiovascular biomarkers. PMID- 9989536 TI - Quality of survival after cardiopulmonary resuscitation. AB - BACKGROUND: Outcome of cardiopulmonary resuscitation (CPR) can be poor, in terms of life expectancy and quality of life. OBJECTIVES: To determine the impact of patient characteristics before, during, and after CPR on these outcomes, and to compare results of the quality-of-life assessment with published studies. METHODS: In a cohort study, we assessed by formal instruments the quality of life, cognitive functioning, depression, and level of dependence of survivors after inhospital CPR. Follow-up was at least 3 months after discharge from the hospital (tertiary care center). RESULTS: Of 827 resuscitated patients, 12% (n = 101) survived to follow-up. Of the survivors, 89% participated in the study. Most survivors were independent in daily life (75%), 17% were cognitively impaired, and 16% had depressive symptoms. Multivariate regression analysis showed that quality of life and cognitive function were determined by 2 factors known before CPR-the reason for admission and age. Factors during and after resuscitation, such as prolonged cardiac arrest and coma, did not significantly determine the quality of life or cognitive functioning of survivors. The quality of life of our CPR survivors was worse compared with a reference group of elderly individuals, but better than that of a reference group of patients with stroke. The quality of life did not importantly differ between the compared studies of CPR survivors. CONCLUSIONS: Cardiopulmonary resuscitation is frequently unsuccessful, but if survival is achieved, a relatively good quality of life can be expected. Quality of life after CPR is mostly determined by factors known before CPR. These findings may be helpful in informing patients about the outcomes of CPR. PMID- 9989537 TI - Prolonged beneficial effects of a home-based intervention on unplanned readmissions and mortality among patients with congestive heart failure. AB - BACKGROUND: A single home-based intervention (HBI) applied immediately after hospital discharge in a cohort of "high-risk" patients with congestive heart failure has been shown to decrease numbers of unplanned readmissions plus out-of hospital deaths during a period of 6 months. The duration of this beneficial effect remains uncertain. METHODS: Hospitalized patients with congestive heart failure who had been randomly assigned to receive either usual care (n=48) or HBI 1 week after discharge (n=49) were subject to an extended follow-up of 18 months. The primary end point of the study was frequency of unplanned readmissions plus out-of-hospital deaths. Secondary end points included total hospital stay, frequency of multiple readmissions, cost of hospital-based care, and total mortality. RESULTS: During 18-month follow-up, HBI patients had fewer unplanned readmissions (64 vs 125; P=.02) and out-of-hospital deaths (2 vs 9; P=.02), representing 1.4+/-1.3 vs 2.7+/-2.8 events per HBI and usual-care patient, respectively (P=.03). The HBI patients also had fewer days of hospitalization (2.5+/-2.7 vs 4.5+/-4.8 per patient; P=.004) and, once readmitted, were less likely to experience 4 or more readmissions (3/31 vs 12/38; P=.03). Hospital based costs were significantly lower among HBI patients (Aust $5100 vs Aust $10600 per patient; P=.02). Unplanned readmission was positively correlated with 14 days or more of unplanned readmission in the 6 months before study entry (odds ratio [OR], 5.4; P=.006). Positive correlates of death were (1) non-English speaking (OR, 4.9; P=.008), (2) 14 days or more of unplanned readmission in the 6 months before study entry (OR, 4.9; P=.008), and (3) left ventricular ejection fraction of 40% or less (OR, 3.0; P=.03); conversely, assignment to HBI was a negative correlate (OR, 0.3; P=.02). CONCLUSIONS: In this controlled study, among a cohort of high-risk patients with congestive heart failure, beneficial effects of a postdischarge HBI were sustained for at least 18 months, with a significant reduction in unplanned readmissions, total hospital stay, hospital-based costs, and mortality. PMID- 9989538 TI - Doxycycline is a cost-effective therapy for hospitalized patients with community acquired pneumonia. AB - BACKGROUND: Doxycycline has a high degree of activity against many common respiratory pathogens and has been used in the outpatient management of lower respiratory tract infections, including pneumonia. OBJECTIVE: To evaluate the efficacy of intravenous doxycycline as empirical treatment in hospitalized patients with mild to moderately severe community-acquired pneumonia. PATIENTS AND METHODS: We conducted a randomized prospective trial to compare the efficacy of intravenous doxycycline with other routinely used antibiotic regimens in 87 patients admitted with the diagnosis of community-acquired pneumonia. Forty-three patients were randomized to receive 100 mg of doxycycline intravenously every 12 hours while 44 patients received other antibiotic(s) (control group). The 2 patient groups were comparable in their clinical and laboratory profiles. RESULTS: The mean+/-SD interval between starting an antibiotic and the clinical response was 2.21+/-2.61 days in the doxycycline group compared with 3.84+/-6.39 days in the control group (P = .001). The mean+/-SD length of hospitalization was 4.14+/-3.08 days in the doxycycline group compared with 6.14+/-6.65 days in the control group (P = .04). The median cost of hospitalization was $5126 in the doxycycline group compared with $6528 in the control group (P = .04). The median cost of antibiotic therapy in the doxycycline-treated patients ($33) was significantly lower than in the control group ($170.90) (P<.001). Doxycycline was as efficacious as the other regimens chosen for the treatment of community acquired pneumonia. CONCLUSION: Doxycycline is an effective and inexpensive therapy for the empirical treatment of hospitalized patients with mild to moderately severe community-acquired pneumonia. PMID- 9989539 TI - Prognosis of diastolic and systolic orthostatic hypotension in older persons. AB - BACKGROUND: Orthostatic hypotension (OH) predicts mortality in hypertensive persons with diabetes mellitus, but no increase in mortality has been found among random samples of home-dwelling persons with OH. We examined the risks of nonvascular and vascular deaths according to different definitions of OH among home-dwelling elderly persons. SUBJECTS AND METHODS: The study population consisted of all persons aged 70 years or older living in 5 rural municipalities (N=969), of whom 833 (86%) participated. Orthostatic tests were successfully carried out in 792 persons by nurse examiners. Orthostatic hypotension was defined as a systolic blood pressure (BP) drop of 20 mm Hg or more or a diastolic BP drop of 10 mm Hg or more 1 minute or 3 minutes after standing up. Nonvascular and vascular deaths during the follow-up period were recorded. Data on diseases, symptoms, medications, the results of clinical examinations and tests, functional ability, and health behavior were collected at the beginning of the follow-up period. RESULTS: Of the sample, 30% had OH: the prevalence of systolic OH 1 minute and 3 minutes after standing up was 22% and 19%, respectively; that of diastolic OH 1 minute and 3 minutes after standing up was 6% for each. No differences in the occurrence of nonvascular deaths were found according to any of these definitions. By Cox multivariate regression analysis, the hazard ratio of vascular death associated with a diastolic BP reduction of 1 mm Hg 1 minute after standing up was 1.02 (P=.03), adjusted for systolic BP postural changes at 1 and 3 minutes and a diastolic BP change at 3 minutes. Adjusted for other significant factors associated with vascular death, the hazard ratio for vascular death associated with diastolic OH 1 minute after standing up was 2.04 (95% confidence interval, 1.01-4.15). The corresponding hazard ratio for systolic OH 3 minutes after standing up was 1.69 (95% confidence interval, 1.02-2.80). Using a cutoff point of 7 mm Hg or greater for a diastolic BP change 1 minute after standing up, the hazard ratio for vascular death was highest: 2.20 (95% confidence interval, 1.23-3.93). By logistic regression analysis, the baseline associates of diastolic OH 1 minute after standing up were dizziness when turning the neck (odds ratio [OR], 2.44), the use of a calcium antagonist (OR, 2.31), the use of a diuretic medication (OR, 2.29), a high systolic BP (OR, 2.23), and a low body mass index (OR, 2.26). The baseline associates of systolic OH 3 minutes after standing up were male sex (OR, 1.52), diabetes mellitus (OR, 1.92), a high systolic BP (OR, 2.91), and a low body mass index (OR, 1.68). CONCLUSIONS: The presence of diastolic OH 1 minute and systolic OH 3 minutes after standing up predict vascular death in older persons. They differ from each other in their prevalence and in several associates, suggesting different pathophysiologic backgrounds. Clinicians should prescribe vasodilating and volume-depleting medications with caution for elderly persons with diastolic OH 1 minute after standing up. Appropriate treatment of hypertension might be the best means to manage the different types of OH with poor vascular prognoses. PMID- 9989540 TI - Drug-induced hypoglycemic coma in 102 diabetic patients. AB - BACKGROUND: Hypoglycemic coma is a continuous threat for diabetic patients treated with insulin and/or oral hypoglycemic agents; it may be associated with substantial morbidity and mortality. METHODS: We retrospectively reviewed our clinical experience with drug-induced hypoglycemic coma during a 7-year period. RESULTS: The study consisted of 102 patients and included 61 females and 41 males. The median age was 72 years. Ninety-two patients suffered from type 2 diabetes mellitus; 10 patients had type 1 diabetes mellitus. The median lowest blood glucose level was 1.77 mmol/L (32 mg/dL). Drug-induced hypoglycemic coma occurred in 99 patients out of the hospital, while 3 patients developed it during hospitalization. Drug-induced hypoglycemic coma occurred in patients undergoing treatment with insulin, glyburide, and combined therapy with insulin and glyburide, insulin and metformin, or glyburide and metformin. Ninety-three patients had at least 1 of the following risk factors: age older than 60 years, renal dysfunction, decreased intake of energy, and infection. Fourteen patients concomitantly received drugs that potentiated hypoglycemia. Forty patients responded to treatment within the first 12 hours, while 62 patients had protracted hypoglycemia of 12 to 72 hours' duration. Morbidity included physical injuries in 7 patients, myocardial ischemia in 2 patients, and stroke in 1 patient. Death occurred in 5 patients. CONCLUSIONS: Hypoglycemic coma is a serious and not an uncommon problem among elderly patients with diabetes mellitus and treated with insulin and/or oral hypoglycemic drugs. Risk factors contribute substantially to the morbidity and mortality of patients with drug-induced hypoglycemic coma. Enhanced therapeutic monitoring may be warranted when hypoglycemic drugs are administered to an elderly patient with the above predisposing factors and potentiating drugs for hypoglycemia. PMID- 9989541 TI - Effects of dietary patterns on blood pressure: subgroup analysis of the Dietary Approaches to Stop Hypertension (DASH) randomized clinical trial. AB - OBJECTIVE: To determine the effects of dietary patterns on blood pressure in subgroups. METHODS: Dietary Approaches to Stop Hypertension (DASH) was a randomized controlled feeding study conducted at 4 academic medical centers. Participants were 459 adults with untreated systolic blood pressure less than 160 mm Hg and diastolic blood pressure 80 to 95 mm Hg. For 3 weeks, participants were fed a "control" diet. They were then randomized to 8 weeks of (1) control diet; (2) a diet rich in fruits and vegetables; or (3) a combination diet rich in fruits, vegetables, and low-fat dairy foods, and reduced in saturated fat, total fat, and cholesterol (the DASH combination diet). Weight and salt intake were held constant. Change in diastolic blood pressure was the primary outcome variable, and systolic blood pressure a secondary outcome. Subgroups analyzed included race, sex, age, body mass index, years of education, income, physical activity, alcohol intake, and hypertension status. RESULTS: The combination diet significantly lowered systolic blood pressure in all subgroups (P<.008), and significantly lowered diastolic blood pressure (P<.01) in all but 2 subgroups. The fruits-and-vegetables diet also reduced blood pressure in the same subgroups, but to a lesser extent. The combination diet lowered systolic blood pressure significantly more in African Americans (6.8 mm Hg) than in whites (3.0 mm Hg), and in hypertensive subjects (11.4 mm Hg) than in nonhypertensive subjects (3.4 mm Hg) (P<.05 for both interactions). CONCLUSIONS: The DASH combination diet, without sodium reduction or weight loss, significantly lowered blood pressure in virtually all subgroups examined, and was particularly effective in African Americans and those with hypertension. The DASH combination diet may be an effective strategy for preventing and treating hypertension in a broad cross section of the population, including segments of the population at highest risk for blood pressure-related cardiovascular disease. PMID- 9989542 TI - Factors associated with implementation of preventive care measures in patients with diabetes mellitus. AB - BACKGROUND: There is only limited information on the extent to which physicians' characteristics affect the level of care and implementation of guidelines in patients with diabetes mellitus. OBJECTIVE: To identify physician characteristics associated with implementation of measures for preventive care in patients with diabetes mellitus and the distribution of implementation of these measures among them. PATIENTS AND METHODS: A retrospective chart audit of 519 patients eligible for health maintenance organization insurance on December 31, 1994, representing patients with diabetes receiving care from 22 primary care physician-providers of a managed care medical group in suburban North Los Angeles, Calif, and seen by physicians between January 1993 and December 1994. A short retroactive questionnaire for participating physicians was also used. The outcome measures were (1) measurement of serum high-density lipoprotein cholesterol; (2) urinalysis for the detection of proteinuria; and (3) ophthalmology referral for dilated fundus examination. RESULTS: Over a period of 2 years 78% of the patients had a high-density lipoprotein cholesterol determination, 80% had a test for proteinuria, and 62% were referred to an ophthalmologist. After adjustment for patient pool differences, physicians who were perceived by the administration of the medical group as "fast," based on a blinded evaluation of their number of patient encounters per unit time, had an odds ratio of 0.60 (95% confidence interval [CI], 0.37-0.95; P=.03) to obtain a high-density lipoprotein cholesterol determination in their patients and an odds ratio of 0.53 (95% CI, 0.32-0.87; P=.01) to test their patients for proteinuria. In patients requiring insulin, of fast physicians, the odds ratio for a referral for ophthalmology screening was 0.25 (95% CI, 0.07-0.85; P= .03). Duration of time in practice of over 15 years and disagreement with practice guidelines were associated with better outcomes. There was no association between physician sex, internal medicine training, or number of patients with diabetes in the practice and the implementation of outcomes. There was a highly significant association between the implementation of an outcome and the implementation of the other 2, resulting in a nonhomogeneous distribution of health care delivery. Physicians' estimate of their rate of implementation of outcomes, as assessed by the questionnaires, overestimated their actual performance while being in proportion with the documented rates. Most physicians took responsibility for the nonimplementation, accepting that it was an oversight on their part as opposed to an encounter with patient resistance. CONCLUSIONS: Most physicians believe that the lack of implementation of the measures for preventive care in patients with diabetes mellitus is an oversight. The oversight is more prevalent in the practices of busy physicians. The result is a nonhomogeneous distribution of health care. Computer reminders might be the solution. PMID- 9989543 TI - Why is HIV rarely transmitted by oral secretions? Saliva can disrupt orally shed, infected leukocytes. AB - BACKGROUND: Oral transmission of human immunodeficiency virus (HIV) by the millions of HIV-infected individuals is a rare event, even when infected blood and exudate is present. Saliva of viremic individuals usually contains only noninfectious components of HIV indicating virus breakdown. OBJECTIVE: To determine whether unknown HIV inhibitory mechanisms may explain the almost complete absence of infectious HIV in the saliva. METHODS: Since most of the infectious HIV that is shed mucosally by asymptomatic individuals is found in, produced by, and transmitted by infected mononuclear leukocytes, we determined whether saliva, which is hypotonic, may disrupt these infected cells, thereby preventing virus multiplication and cell-to-cell transmission of HIV. Specifically, we measured (1) whether mononuclear leukocytes were lysed by saliva and (2) whether the lysis by saliva inhibits the multiplication of HIV and other viruses in infected leukocytes and other cells. RESULTS: Saliva rapidly disrupted 90% or more of blood mononuclear leukocytes and other cultured cells. Concomitantly, there was a 10000-fold or higher inhibition of the multiplication of HIV and surrogate viruses. Further experiments indicated that the cell disruption is due to the hypotonicity of saliva: CONCLUSIONS: Hypotonic disruption may be a major mechanism by which saliva kills infected mononuclear leukocytes and prevents their attachment to mucosal epithelial cells and production of infectious HIV, thereby preventing transmission. Implications for the known oral HIV transmission by milk and seminal fluid, as well as potential oral transmission to contacts and health care workers, are considered. This effective salivary defense may be applicable medically to interdict vaginal, rectal, and oral transmission of HIV by infected cells in seminal fluid or milk by the use of anticellular substances. PMID- 9989544 TI - Thrombotic thrombocytopenic purpura associated with ticlopidine use: a report of 3 cases and review of the literature. AB - Ticlopidine hydrochloride is an antiplatelet agent used for an increasing number of indications, including cerebrovascular disease, unstable angina, coronary artery stenting, and peripheral vascular bypass grafting. It has uncommon but severe hematologic effects, including thrombotic thrombocytopenic purpura. We report 3 new cases of ticlopidine-associated thrombotic thrombocytopenic purpura and review the English-language literature. Of the 13 patients described (10 from published articles), an equal number were women and men. The median age of the women was 50 years, and that of the men was 72 years. Thrombotic thrombocytopenic purpura occurred within 2 to 8 weeks of starting ticlopidine therapy. Survivors received plasma therapy, but of the 4 who died, 3 had received platelet transfusions. With discontinuation of the drug and prompt plasma exchange therapy, mortality was comparable to that seen with idiopathic thrombotic thrombocytopenic purpura, and relapse was uncommon. Physicians and patients should be aware of this potentially fatal but treatable complication of ticlopidine therapy. PMID- 9989545 TI - Atherosclerosis and the immune system. PMID- 9989546 TI - Haemophilus influenzae pyelonephritis in adults. PMID- 9989547 TI - Influenza vaccination in bedridden patients. PMID- 9989548 TI - Accuracy of an automated blood pressure device under conditions of the head-up tilt test. PMID- 9989549 TI - Research in affective disorders comes of age. PMID- 9989550 TI - Images in neuroscience. Brain development, X: pruning during development. PMID- 9989551 TI - Sympathoadrenal hyperactivity and the etiology of neuroleptic malignant syndrome. AB - OBJECTIVE: The author's goal was to develop a pathophysiological model for neuroleptic malignant syndrome with greater explanatory power than the alternative hypotheses of hypothalamic dopamine antagonism (elevated set point) and direct myotoxicity (malignant hyperthermia variant). METHOD: Published clinical findings on neuroleptic malignant syndrome were integrated with data from human and animal studies of muscle physiology, thermoregulation, and autonomic nervous system function. RESULTS: The data show that the sympathetic nervous system's latent capacity for autonomous activity is expressed when tonic inhibitory inputs from higher central nervous system centers are disrupted. These tonic inhibitory inputs are relayed to preganglionic sympathetic neurons by way of dopaminergic hypothalamospinal tracts. The sympathetic nervous system mediates hypothalamic coordination of thermoregulatory activity and is a primary regulator of muscle tone and thermogenesis, augmenting both of these when stimulated. In addition, the sympathetic nervous system modulates all of the other end-organs that function abnormally in neuroleptic malignant syndrome. CONCLUSIONS: There is substantial evidence to support the hypothesis that dysregulated sympathetic nervous system hyperactivity is responsible for most, if not all, features of neuroleptic malignant syndrome. A predisposition to more extreme sympathetic nervous system activation and/or dysfunction in response to emotional or psychological stress may constitute a trait vulnerability for neuroleptic malignant syndrome, which, when coupled with state variables such as acute psychic distress or dopamine receptor antagonism, produces the clinical syndrome of neuroleptic malignant syndrome. This hypothesis provides a more comprehensive explanation for existing clinical data than do the current alternatives. PMID- 9989553 TI - Inadequacy of antidepressant treatment for patients with major depression who are at risk for suicidal behavior. AB - OBJECTIVE: The authors' goal was to determine whether suicide attempters with major depression received more intensive antidepressant treatment than depressed patients who had not attempted suicide. METHOD: One hundred eighty inpatients who met DSM-III-R criteria for a major depressive episode according to the Structured Clinical Interview for DSM-III-R were enrolled in the study. All patients were assessed for lifetime history of suicide attempts. Depressive symptoms at the index hospitalization were assessed with the Hamilton Depression Rating Scale and the Beck Depression Inventory. Strength of antidepressant treatment over the 90 days preceding the hospitalization was scored by using the Antidepressant Treatment History Form. RESULTS: A large majority of the depressed patients with a history of suicide attempts, who were at higher risk for future suicide and suicide attempts, received inadequate treatment. Similarly, most of the depressed patients at lower risk for suicide attempts also received inadequate treatment. CONCLUSIONS: Major depression is undertreated pharmacologically, regardless of history of suicide attempt. Some suicide attempts may be preventable if the problem of underdiagnosis and undertreatment of depression can be overcome by psychoeducation for health professionals and the public. PMID- 9989552 TI - Toward a clinical model of suicidal behavior in psychiatric patients. AB - OBJECTIVE: Risk factors for suicide attempts have rarely been studied comprehensively in more than one psychiatric disorder, preventing estimation of the relative importance and the generalizability of different putative risk factors across psychiatric diagnoses. The authors conducted a study of suicide attempts in patients with mood disorders, psychoses, and other diagnoses. Their goal was to determine the generalizability and relative importance of risk factors for suicidal acts across diagnostic boundaries and to develop a hypothetical, explanatory, and predictive model of suicidal behavior that can subsequently be tested in a prospective study. METHOD: Following admission to a university psychiatric hospital, 347 consecutive patients who were 14-72 years old (51% were male and 68% were Caucasian) were recruited for study. Structured clinical interviews generated axis I and axis II diagnoses. Lifetime suicidal acts, traits of aggression and impulsivity, objective and subjective severity of acute psychopathology, developmental and family history, and past substance abuse or alcoholism were assessed. RESULTS: Objective severity of current depression or psychosis did not distinguish the 184 patients who had attempted suicide from those who had never attempted suicide. However, higher scores on subjective depression, higher scores on suicidal ideation, and fewer reasons for living were reported by suicide attempters. Rates of lifetime aggression and impulsivity were also greater in attempters. Comorbid borderline personality disorder, smoking, past substance use disorder or alcoholism, family history of suicidal acts, head injury, and childhood abuse history were more frequent in suicide attempters. CONCLUSIONS: The authors propose a stress-diathesis model in which the risk for suicidal acts is determined not merely by a psychiatric illness (the stressor) but also by a diathesis. This diathesis may be reflected in tendencies to experience more suicidal ideation and to be more impulsive and, therefore, more likely to act on suicidal feelings. Prospective studies are proposed to test this model. PMID- 9989554 TI - Prospective study of fluoxetine treatment and suicidal behavior in affectively ill subjects. AB - OBJECTIVE: There has been speculation in the literature about a link between fluoxetine use and suicidal behavior. The authors of this study hypothesized that there is no elevation in risk of suicidal behavior associated with use of fluoxetine. METHOD: The data come from the National Institute of Mental Health Collaborative Depression Study, a prospective, naturalistic follow-up of persons who presented for treatment of affective disorders. The analyses included data on 643 subjects who were followed up after fluoxetine was approved by the Food and Drug Administration in December 1987 for the treatment of depression. RESULTS: Nearly 30% (N = 185) of the study group was treated with fluoxetine at some point during the follow-up period. Relative to the other subjects, those who were subsequently treated with fluoxetine had onset of affective illness at a younger age and, after intake into the study and before 1988, had elevated rates of suicide attempts before fluoxetine treatment. A mixed-effects survival analysis that incorporated treatment exposure time, multiple treatment trials, and multiple suicide attempts per subject showed that relative to no treatment, use of fluoxetine and use of other somatic antidepressants were associated with nonsignificant reductions in the likelihood of suicide attempts or completions. Severity of psychopathology was strongly associated with elevated risk, and each suicide attempt after intake into the Collaborative Depression Study was associated with a marginally significant increase in risk of suicidal behavior. CONCLUSIONS: The results do not support the speculation that fluoxetine increases the risk of suicide. Rather, there was a nonsignificant reduction in risk of suicidal behavior among patients treated with fluoxetine, even though those subjects were more severely ill before treatment with fluoxetine. PMID- 9989555 TI - Treatment of bereavement-related major depressive episodes in later life: a controlled study of acute and continuation treatment with nortriptyline and interpersonal psychotherapy. AB - OBJECTIVE: The authors tested the hypothesis that nortriptyline and interpersonal psychotherapy, alone and in combination, are superior to placebo in achieving remission of bereavement-related major depressive episodes. METHOD: Eighty subjects, aged 50 years and older, with major depressive episodes that began within 6 months before or 12 months after the loss of a spouse or significant other were randomly assigned to a 16-week doubleblind trial of one of four treatment conditions: nortriptyline plus interpersonal psychotherapy (N = 16), nortriptyline alone in a medication clinic (N = 25), placebo plus interpersonal psychotherapy (N = 17), or placebo alone in a medication clinic (N = 22). The protocol required that the acute-phase double-blind treatment be ended after 8 weeks if Hamilton depression scale ratings had not improved by 50%. Remission was defined as a 17-item Hamilton scale score of 7 or lower for 3 consecutive weeks. RESULTS: The rate of remission for nortriptyline plus interpersonal psychotherapy was 69% (N = 11); for medication clinic, nortriptyline, 56% (N = 14); for placebo plus interpersonal psychotherapy, 29% (N = 5); and for medication clinic, placebo, 45% (N = 10). In a generalized logit model, there was a significant effect of nortriptyline over placebo but no interpersonal psychotherapy effect and no nortriptyline-by-interpersonal psychotherapy interaction. Rates of all cause attrition were lowest in the nortriptyline plus interpersonal psychotherapy group. CONCLUSIONS: Nortriptyline was superior to placebo in achieving remission of bereavement-related major depressive episodes. The combination of medication and psychotherapy was associated with the highest rate of treatment completion. These results support the use of pharmacologic treatment of major depressive episodes in the wake of a serious life stressor such as bereavement. PMID- 9989556 TI - Functional MRI study of the cognitive generation of affect. AB - OBJECTIVE: The authors investigated, by whole brain functional magnetic resonance imaging (MRI), the neural substrate underlying processing of emotion-related meanings. METHOD: Six healthy subjects underwent functional MRI while viewing 1) alternating blocks of pairs of pictures and captions evoking negative feelings and the same materials irrelevantly paired to produce less emotion (reference pairs); 2) alternating blocks of picture-caption pairs evoking positive feelings and the same materials irrelevantly paired to produce less emotion; and 3) alternating blocks of picture-caption pairs evoking positive feelings and picture caption pairs evoking negative feelings. RESULTS: Compared with the reference picture-caption pairs, negative pairs activated the right medial and middle frontal gyri, right anterior cingulate gyrus, and right thalamus. Compared with the reference picture-caption pairs, positive pairs activated the right and left insula, right inferior frontal gyrus, left splenium, and left precuneus. Compared with the negative picture-caption pairs, positive pairs activated the right and left medial frontal gyri, right anterior cingulate gyrus, right precentral gyrus, and left caudate. CONCLUSIONS: Contrasts of both 1) negative and reference picture-caption pairs and 2) positive and negative picture-caption pairs activated networks involving similar areas in the medial frontal gyrus (Brodmann's area 9) and right anterior cingu-late gyrus (areas 24 and 32). The area 9 sites activated are strikingly similar to sites activated in related positron emission tomography experiments. Activation of these same sites by a range of evoked affects, elicited by different methods, is consistent with areas within the medial prefrontal cortex mediating the processing of affect-related meanings, a process common to many forms of emotion production. PMID- 9989557 TI - Amygdalar volume and emotional memory in Alzheimer's disease. AB - OBJECTIVE: Everyday experience suggests that highly emotional events are often the most memorable. Experimental work in animals and humans has demonstrated that the amygdaloid complex plays a crucial role in emotional memory, i.e., memory of events arousing strong emotions. The aim of this study was to elucidate the relationship between medial temporal damage and impaired memory of real-life emotional events in patients with Alzheimer's disease. METHOD: In 36 patients with probable Alzheimer's disease who experienced the 1995 earthquake in Kobe, Japan, memories of events surrounding the earthquake were examined as an index of emotional memory with the use of a semistructured interview, and amygdalar and hippocampal volumes were quantified by magnetic resonance imaging. The effects of the atrophy of these structures on recall performance were determined by multiple regression analysis. RESULTS: Irrespective of generalized brain atrophy and cognitive impairments, emotional memory was correlated more with normalized amygdalar volume (right and left averaged) than with normalized hippocampal volume. General knowledge of the earthquake was correlated with neither amygdalar nor hippocampal volume. CONCLUSIONS: The results indicate that impairment of emotional event memory in patients with Alzheimer's disease is related to intensity of amygdalar damage and provide evidence of the amygdala's involvement in emotional memory in humans. PMID- 9989558 TI - Caffeine intake, tolerance, and withdrawal in women: a population-based twin study. AB - OBJECTIVE: Caffeine is by far the most commonly consumed psychoactive substance. The use and abuse of most other licit and illicit psychoactive drugs have been shown to be substantially heritable. However, the impact of genetic factors on caffeine consumption, heavy use, intoxication, tolerance, and withdrawal is largely unknown. METHOD: Caffeine consumption, in the form of brewed coffee, instant coffee, tea, and caffeinated soft drinks, as well as caffeine intoxication, tolerance, and withdrawal, were assessed by personal interviews of 1,934 individual twins from female-female pairs ascertained from the population based Virginia Twin Registry. The sample included both members of 486 monozygotic and 335 dizygotic pairs. Twin resemblance was assessed by probandwise concordance, odds ratios, and tetrachoric correlations. Biometrical model fitting was also performed. RESULTS: The resemblance in twin pairs for total caffeine consumption, heavy caffeine use, caffeine intoxication, caffeine tolerance, and caffeine withdrawal was substantially greater in monozygotic than in dizygotic twin pairs. Model fitting suggested that twin resemblance for these measures could be ascribed solely to genetic factors, with estimated broad heritabilities of between 35% and 77%. CONCLUSIONS: Caffeine is an addictive psychoactive substance. Similar to previous findings with other licit and illicit psychoactive drugs, individual differences in caffeine use, intoxication, tolerance, and withdrawal are substantially influenced by genetic factors. PMID- 9989559 TI - Human brain metabolic response to caffeine and the effects of tolerance. AB - OBJECTIVE: Since there is limited information concerning caffeine's metabolic effects on the human brain, the authors applied a rapid proton echo-planar spectroscopic imaging technique to dynamically measure regional brain metabolic responses to caffeine ingestion. They specifically measured changes in brain lactate due to the combined effects of caffeine's stimulation of glycolysis and reduction of cerebral blood flow. METHOD: Nine heavy caffeine users and nine caffeine-intolerant individuals, who had previously discontinued or substantially curtailed use of caffeinated products because of associated anxiety and discomforting physiological arousal, were studied at baseline and then during 1 hour following ingestion of caffeine citrate (10 mg/kg). To assess state-trait contributions and the effects of caffeine tolerance, five of the caffeine users were restudied after a 1- to 2-month caffeine holiday. RESULTS: The caffeine intolerant individuals, but not the regular caffeine users, experienced substantial psychological and physiological distress in response to caffeine ingestion. Significant increases in global and regionally specific brain lactate were observed only among the caffeine-intolerant subjects. Reexposure of the regular caffeine users to caffeine after a caffeine holiday resulted in little or no adverse clinical reaction but significant rises in brain lactate which were of a magnitude similar to that observed for the caffeine-intolerant group. CONCLUSIONS: These results provide direct evidence for the loss of caffeine tolerance in the human brain subsequent to caffeine discontinuation and suggest mechanisms for the phenomenon of caffeine intolerance other than its metabolic effects on elevating brain lactate. PMID- 9989560 TI - Striatal dopaminergic abnormalities in human cocaine users. AB - OBJECTIVE: Previous human postmortem experiments have shown an abnormally high number of dopamine uptake sites in the striatum of chronic cocaine users, which might contribute to cocaine withdrawal symptoms such as depression and suicidality. Previous inconsistencies in results were perhaps related to selective radioligand affinity changes or a coexisting loss of dopamine neurons. METHOD: In the present study, binding of the cocaine analog [3H]WIN 35428 to the dopamine transporter was assayed in postmortem striatal samples from 15 cocaine using subjects and 15 matched comparison subjects to determine whether there were differences in number of binding sites or in affinity. Binding to the vesicular monoamine transporter, a measure of total dopaminergic terminals, was also assessed by using the radioligand (+)-[3H]dihydrotetrabenazine (DTBZ). RESULTS: Striatal [3H]WIN 35428 binding sites were significantly more numerous in the cocaine users: the mean Bmax value was 9.0 fmol bound/microg protein (SD = 2.8) for the cocaine users but only 6.0 (SD = 1.7) for the comparison subjects. Severity of chronic cocaine use was significantly related to [3H]WIN 35428 binding level. [3H]DTBZ binding was significantly lower in the cocaine users (mean = 330 nCi/mg, SD = 42) than in the comparison subjects (mean = 374, SD = 68). CONCLUSIONS: The present results confirm that cocaine users have a high number of dopamine transporter binding sites on dopaminergic neurons, despite an apparent low number of total dopamine terminals. These abnormalities may contribute to the abnormalities in subjective experience and behavior characteristic of chronic cocaine abusers. PMID- 9989561 TI - Heritability of anxiety sensitivity: a twin study. AB - OBJECTIVE: In attempting to explain the familial predisposition to panic disorder, most studies have focused on the heritability of physiologic characteristics (e.g., CO2 sensitivity). A heretofore unexplored possibility is that a psychological characteristic that predisposes to panic-anxiety sensitivity might be inherited. In this study, the authors examined the heritability of anxiety sensitivity through use of a twin group. METHOD: Scores on the Anxiety Sensitivity Index were examined in a group of 179 monozygotic and 158 dizygotic twin pairs. Biometrical model fitting was conducted through use of standard statistical methods. RESULTS: Broad heritability estimate of the Anxiety Sensitivity Index as a unifactorial construct was 45%. Additive genetic effects and unique environmental effects emerged as the primary influences on anxiety sensitivity. There was no evidence of genetic discontinuity between normal and extreme scores on the Anxiety Sensitivity Index. CONCLUSIONS: This study suggests that one psychological risk factor for the development of panic disorder-anxiety sensitivity-may have a heritable component. As such, anxiety sensitivity should be considered in future research on the heritability of panic disorder. PMID- 9989562 TI - Cerebral blood flow and personality: a positron emission tomography study. AB - OBJECTIVE: This study sought to describe brain regions associated with the personality dimension of introversion/extraversion. METHOD: Measures of cerebral blood flow (CBF) were obtained from 18 healthy subjects by means of [150]H20 positron emission tomography. Correlations of regional CBF with introversion/extraversion were calculated, and a three-dimensional map of those correlations was generated. RESULTS: Overall, introversion was associated with increased blood flow in the frontal lobes and in the anterior thalamus. Regions in the anterior cingulate gyrus, the temporal lobes, and the posterior thalamus were found to be correlated with extraversion. CONCLUSIONS: The findings of the study lend support to the notion that introversion is associated with increased activity in frontal lobe regions. Moreover, the study suggests that individual differences in introversion and extraversion are related to differences in a fronto-striato-thalamic circuit. PMID- 9989563 TI - Revising and assessing axis II, Part I: developing a clinically and empirically valid assessment method. AB - OBJECTIVE: Personality pathology is difficult to measure. Current instruments have problems with validity and rely on a direct-question format that may be inappropriate for the assessment of personality. In addition, they are designed specifically to address current DSM-IV categories and criteria, which limits their utility in making meaningful revisions of those criteria. These problems suggest the need for consideration of alternative approaches to assessing and revising axis II. METHOD: This article describes the development and validation of an assessment tool designed to allow clinicians to provide detailed, clinically rich personality descriptions in a systematic and quantifiable form (the Shedler-Westen Assessment Procedure, or SWAP-200). A total of 797 randomly selected psychiatrists and psychologists used the SWAP-200 to describe either an actual patient or a hypothetical, prototypical patient with one of 14 personality disorders (one of the 10 DSM-IV axis II disorders or one of four disorders included in the appendix or in DSM-III-R) or a healthy, high-functioning patient. RESULTS: The data yielded aggregated descriptions of actual patients in each diagnostic category (N = 530) as well as aggregated descriptions of hypothetical, prototypical patients (N = 267). SWAP-200 descriptions of patients with personality disorders showed high convergent and discriminant validity on a variety of criteria. The diagnostic procedure lends itself to both categorical and dimensional personality disorder diagnoses. Descriptions of individual patients resemble MMPI profiles, based on the degree of match between the patient's profile and a criterion group, except that they are based on clinician observation rather than self-report. CONCLUSIONS: The SWAP-200 represents an approach to the measurement and classification of personality disorders that has potential for refining axis II categories and criteria empirically in ways that are both psychometrically and clinically sound. PMID- 9989564 TI - Revising and assessing axis II, Part II: toward an empirically based and clinically useful classification of personality disorders. AB - OBJECTIVE: The DSM-IV classification of personality disorders has not proven satisfying to either researchers or clinicians. Incremental changes to categories and criteria using structured interviews may no longer be useful in attempting to refine axis II. An alternative approach that quantifies clinical observation may prove useful in developing a clinically rich, useful, empirically grounded classification of personality pathology. METHOD: A total of 496 experienced psychiatrists and psychologists used the Shedler-Westen Assessment Procedure-200 (SWAP-200) to describe current patients diagnosed with axis II personality disorders. The SWAP-200 is an assessment tool that allows clinicians to provide detailed, clinically rich descriptions of patients in a systematic and quantifiable form. A statistical technique, Q-analysis, was used to identify naturally occurring groupings of patients with personality disorders, based on shared psychological features. The resulting groupings represent an empirically derived personality disorder taxonomy. RESULTS: The analysis found 11 naturally occurring diagnostic categories, some of which resembled current axis II categories and some of which did not. The findings suggest that axis II falls short in its attempt to "carve nature at the joints": In some cases it puts patients who are psychologically dissimilar in the same diagnostic category, and in others it makes diagnostic distinctions where none likely exist. It also fails to recognize a large category of patients best characterized as having a dysphoric personality constellation. The empirically derived classification system appears to be more faithful to the clinical data and to avoid many problems inherent in the current axis II taxonomy. CONCLUSIONS: The approach presented here may be helpful in refining the existing taxonomy of personality disorders and moving toward a system of classification that lies on a firmer clinical and empirical foundation. In addition, it can help to bridge the gap that often exists between research and clinical approaches to personality pathology. PMID- 9989565 TI - Clinical and theoretical implications of 5-HT2 and D2 receptor occupancy of clozapine, risperidone, and olanzapine in schizophrenia. AB - OBJECTIVE: Dopamine D2 receptor occupancy measurements provide a valid predictor of antipsychotic response, extrapyramidal side effects, and elevation of prolactin levels. The new antipsychotics clozapine, risperidone, and olanzapine obtain antipsychotic response with few extrapyramidal side effects and little prolactin elevation. The purpose of this study was to compare the D2 and serotonin 5-HT2 receptor occupancies of these drugs in patients receiving multiple-dose, steady-state regimens. METHOD: Forty-four patients with schizophrenia (16 taking risperidone, 2-12 mg/day; 17 taking olanzapine, 5-60 mg/day; and 11 taking clozapine, 75-900 mg/day) had their D2 and 5-HT2 occupancies determined with the use of [11C]raclopride and [18F]setoperone, respectively, and positron emission tomography imaging. RESULTS: Clozapine showed a much lower D2 occupancy (16%-68%) than risperidone (63%-89%) and olanzapine (43%-89%). Risperidone and olanzapine gave equal D2 occupancies at doses of 5 and 20 mg/day, respectively. All three drugs showed greater 5-HT2 than D2 occupancy at all doses, although the difference was greatest for clozapine. CONCLUSIONS: Clozapine, at doses known to be effective in routine clinical settings, showed a D2 occupancy clearly lower than that of typical antipsychotics, while risperidone and olanzapine at their usual clinical doses gave the same level of D2 occupancy as low-dose typical antipsychotics. The results also suggest that some previous clinical comparisons of antipsychotics may have been confounded by different levels of D2 occupancy. Clinical comparisons of these drugs, matching for D2 occupancy, may provide a better measure of their true "atypicality" and will help in understanding the contribution of non-D2 receptors to antipsychotic effects. PMID- 9989566 TI - Clozapine and risperidone in chronic schizophrenia: effects on symptoms, parkinsonian side effects, and neuroendocrine response. AB - OBJECTIVE: Clozapine and risperidone were the first two "second-generation" antipsychotic drugs approved for schizophrenia. There is currently little information about their comparative efficacy from head-to-head clinical trials. The purpose of this study was to examine the comparative efficacy of clozapine and risperidone for positive and negative symptoms, depression, parkinsonian side effects, and indexes of neuroendocrine function in schizophrenic patients who met a priori criteria for partial response to traditional neuroleptic agents. METHOD: After a baseline fluphenazine treatment period, 29 patients participated in a 6 week, double-blind, parallel-group comparison of the effects of these agents. RESULTS: Clozapine was superior to risperidone for positive symptoms and parkinsonian side effects, but there were no significant differences between the drugs on two measures of negative symptoms, Brief Psychiatric Rating Scale total scores, and depression scores. The clozapine patients, but not the risperidone patients, demonstrated significant reductions from the fluphenazine baseline in positive symptoms, total symptoms, and depression. In addition, clozapine produced fewer effects on plasma prolactin than risperidone or fluphenazine. The mean daily doses during week 6 of the trial were 403.6 mg of clozapine and 5.9 mg of risperidone. CONCLUSIONS: The findings from this study indicate that these drugs have both important differences and similarities in their comparative efficacy in chronically ill, partially responsive patients with schizophrenia. Further research on second-generation antipsychotic drugs in this patient population that addresses key methodological issues, such as optimal dose and treatment duration, are needed. PMID- 9989567 TI - Diazepam treatment of early signs of exacerbation in schizophrenia. AB - OBJECTIVE: Therapeutic intervention at the earliest phase of symptom exacerbation in schizophrenia is an important clinical need, but specific pharmacotherapeutic interventions for this phase of illness have not been established. This study examined diazepam efficacy for this phase of treatment. METHOD: A double-blind, randomized clinical trial with 53 schizophrenic patients compared diazepam with placebo (with fluphenazine treatment for a comparison group). Treatment was initiated at the earliest signs of exacerbation, and symptom progression was the dependent measure used to evaluate efficacy. RESULTS: Diazepam was statistically superior to placebo in preventing symptom progression and was comparable to fluphenazine. CONCLUSIONS: Efficacy data support the use of diazepam in treating prodromal and early warning signs of symptom exacerbation in schizophrenia. This therapeutic strategy may be especially important for patients who refuse antipsychotic drugs or as a supplemental approach in a treatment plan that emphasizes low-dose antipsychotic therapy. PMID- 9989568 TI - When religion collides with medicine. PMID- 9989570 TI - Incidence of tardive dyskinesia in early stages of low-dose treatment with typical neuroleptics in older patients. AB - OBJECTIVE: The authors studied the risk of tardive dyskinesia for older patients in the early stages of treatment with typical neuroleptics. METHOD: They examined the cumulative incidence of tardive dyskinesia 1, 3, 6, 9, and 12 months after the institution of neuroleptic therapy among 307 psychiatric outpatients over age 45. The patients' median dose was 68.4 mg/day of chlorpromazine equivalent. RESULTS: In the patients who had never received neuroleptics at baseline (N = 87), the mean cumulative incidence of tardive dyskinesia was 3.4% and 5.9% at 1 and 3 months, respectively. There was no significant difference in the 12-month cumulative incidence of tardive dyskinesia among patients who had been neuroleptic-naive at baseline (22.3%) and the 89 patients who had received neuroleptics before baseline for 1-30 days (24.6%); however, the 131 patients who had received neuroleptics before baseline for more than 30 days tended to have a greater cumulative 12-month incidence of tardive dyskinesia (36.9%). CONCLUSIONS: The risk of tardive dyskinesia in older outpatients is high, even with relatively short treatment with low doses of conventional neuroleptics. PMID- 9989571 TI - Body weight and leptin plasma levels during treatment with antipsychotic drugs. AB - OBJECTIVE: Leptin is produced by fat cells and is presumed to signal the size of the adipose tissue to the brain. The authors investigated whether antipsychotic drugs that often induce weight gain affect circulating levels of leptin. METHOD: Weight, body mass index, and leptin plasma level were measured weekly over 4 weeks in psychiatric inpatients who received clozapine (N = 11), olanzapine (N = 8), haloperidol (N = 13), or no psychopharmacological treatment (N = 12). RESULTS: In patients receiving clozapine or olanzapine, significant increases in weight, body mass index, and leptin level were found, whereas these measures remained stable in patients who received haloperidol or no pharmacological treatment. CONCLUSIONS: Weight gain induced by clozapine or olanzapine appears to be associated with an increase in leptin level that cannot be attributed to dietary changes upon hospitalization. PMID- 9989572 TI - Prevalence of depressive symptoms early in the course of schizophrenia. AB - OBJECTIVE: The rate of depressive symptoms early in the course of schizophrenia was determined. METHOD: Seventy subjects with recent-onset schizophrenia were followed for 5 years by using semistructured interview instruments. The initial assessment included ratings of each criterion A symptom of a DSM-III-R major depressive episode. The rates of symptoms experienced with at least moderate severity were calculated, and an algorithm based on DSM identified subjects meeting the criteria for a major depressive episode. RESULTS: Four symptoms were present to at least a moderate degree in a majority of subjects, while no symptom was present in fewer than 12% of subjects. More than one-third of the subjects met the algorithmic criteria for a major depressive episode at the time of intake. CONCLUSIONS: Depressive symptoms are common early in the course of schizophrenia. This finding is consistent with other recent data and has potential implications for current diagnostic and treatment practices. PMID- 9989573 TI - B lymphocyte antigen D8/17 and repetitive behaviors in autism. AB - OBJECTIVE: Monoclonal antibody D8/17 identifies a B lymphocyte antigen with expanded expression in rheumatic fever, Sydenham's chorea, and subgroups of obsessive-compulsive disorder and Tourette's syndrome with repetitive behaviors. The authors examined the rate of D8/17 expression in children with autism and its correlation with severity of repetitive behaviors. METHOD: Blood samples from 18 patients with autism and 14 comparable medically ill children were evaluated for percentage of D8/17-positive B cells by immunofluorescence and for streptococcal antibodies. Severity of repetitive behaviors was also determined. RESULTS: The frequency of individuals with > or =11% D8/17-positive cells was significantly higher in the autistic patients (78%) than the comparison subjects (21%), severity of repetitive behaviors significantly correlated with D8/17 expression, and D8/17-positive patients had significantly higher compulsion scores than D8/17 negative patients. CONCLUSIONS: D8/17 expression is high in patients with autism and may serve as a marker for compulsion severity within autism. PMID- 9989574 TI - Attitudes toward DSM-IV dissociative disorders diagnoses among board-certified American psychiatrists. AB - OBJECTIVE: The authors assessed the opinions of American psychiatrists regarding the diagnostic status and scientific validity of the DSM-IV categories of dissociative amnesia and dissociative identity disorder. METHOD: A one-page questionnaire was mailed to a random national sample of 367 board-certified American psychiatrists. RESULTS: Three hundred one responses were received-a rate of 82%. Only about one-third of respondents replied that dissociative amnesia and dissociative identity disorder should be included without reservations in DSM-IV; a larger proportion replied that these categories should be included only as proposed diagnoses. Only about one-quarter of respondents felt that diagnoses of dissociative amnesia and dissociative identity disorder were supported by strong evidence of scientific validity. CONCLUSIONS: Among board-certified American psychiatrists, there currently appears to be little consensus regarding the diagnostic status or scientific validity of dissociative amnesia and dissociative identity disorder. PMID- 9989575 TI - Are psychiatrists cost-effective? An analysis of integrated versus split treatment. AB - OBJECTIVE: Managed care organizations prefer putatively less expensive split treatment, i.e., a psychopharmacologist plus a non-M.D. psychotherapist. In this study the cost of integrated care by a psychiatrist was compared with split care. METHOD: Using 1998 fee schedules of seven large managed care organizations (with 54.3% market share and 67.8 million lives) plus Medicare (37 million people), the author modeled clinical scenarios of psychotherapy alone, medication alone, and combined treatment provided by a psychiatrist or split with a psychologist or social worker. RESULTS: Brief psychotherapy by a social worker was the least expensive treatment. When treatment required both psychotherapy and medication, combined treatment by a psychiatrist cost about the same or less than split treatment with a social worker psychotherapist; it was usually less expensive than split treatment with a psychologist psychotherapist. CONCLUSIONS: The integrated biopsychosocial model practiced by psychiatry is both theoretically and economically the preferred model when combined treatment is needed. PMID- 9989577 TI - There is nothing new under the sun. PMID- 9989576 TI - Risperidone for exclusively negative symptoms. PMID- 9989578 TI - Smoking cessation and anxiety. PMID- 9989579 TI - Managed care and psychotherapy for schizophrenia. PMID- 9989580 TI - Reactivity of glutaredoxins 1, 2 and 3 from Escherichia coli and protein disulfide isomerase towards glutathionyl-mixed disulfides in ribonuclease A. AB - We have examined the activity of protein disulfide isomerase (PDI) and glutaredoxin (Grx) 1, 2 and 3 from Escherichia coli to catalyze the cleavage of glutathionylated ribonuclease A (RNase-SG) by 1 mM GSH to yield reduced RNase. Apparent Km values for RNase-SG were similar, 2-10 microM, for Grx 1, 3 and PDI but Grx I and Grx 3 showed 500-fold higher turnover numbers than PDI. The atypical Grx 2 also catalyzed deglutathionylation by GSH, but had higher Km and apparent turnover number values compared to the two classical Grx. Refolding of RNase in a glutathione redox buffer was catalyzed by PDI. However, it could be measured only after a characteristic lag phase that was shortened by all three E. coli Grxs in a concentration-dependent manner. A role of the glutaredoxin mechanism in the endoplasmic reticulum is suggested. PMID- 9989581 TI - Calpain-induced proteolysis of beta-spectrins. AB - The calcium-activated neutral protease calpain is activated in several pathological conditions. Calpain usually hydrolyses one or only a few peptide bonds in its substrate. One prominent substrate for calpain is spectrin and it has been shown that alpha-spectrin is the preferred substrate. We now show that the beta-chain of spectrin is also a substrate for calpain proteolysis, and that the cleavage site in each beta-subunit is located at the very C-terminal part of the molecule. Surprisingly, beta1sigma-spectrin is cleaved at a different site than betaIsigma2- and betaIIsigma1-spectrins despite their high degree of sequence identity. PMID- 9989582 TI - FTDP-17 mutations N279K and S305N in tau produce increased splicing of exon 10. AB - Missense mutations and intronic mutations in the tau gene cause frontotemporal dementia and Parkinsonism linked to chromosome 17 (FTDP-17). Known missense mutations reduce the ability of tau to promote microtubule assembly. Intronic mutations lead to increased mRNA splicing of the alternatively spliced exon 10, resulting in an overproduction of tau isoforms with four microtubule-binding repeats. We show here that the recently identified FTDP-17 missense mutations N279K and S305N do not reduce the ability of tau to promote microtubule assembly. Instead they lead to increased splicing of exon 10, like the intronic mutations. The N279K and S305N mutations define a class of missense mutations in tau whose primary effects are at the RNA level. PMID- 9989583 TI - Identification and structural characterization of two genes encoding glutamate transporter homologues differently expressed in the nervous system of Drosophila melanogaster. AB - In vertebrates, excitatory amino acid transporters (EAATs) are believed to mediate the removal of glutamate released at excitatory synapses and to maintain extracellular concentrations of this neurotransmitter below excitotoxic levels. Glutamate is also used in insects as an excitatory neurotransmitter at the neuromuscular junction and probably in the central nervous system where its role remains to be established. We report the molecular characterization and developmental expression pattern of two Drosophila cDNAs: dEAATI, which has recently been identified as a high affinity glutamate transporter [1], and dEAAT2, a novel protein sharing strong homology to dEAATI and to the mammalian EAAT protein family. The developmental expression pattern of the two Drosophila EAAT genes has been compared by Northern blot analysis and whole-mount in situ hybridizations. The two transporters are transcribed in distinct cell types of the nervous system and are strongly expressed in the adult visual system. PMID- 9989584 TI - The intramitochondrial ATP/ADP-ratio controls cytochrome c oxidase activity allosterically. AB - Recently the signal transduction function for oxidative phosphorylation was found to be second order in ADP [Jeneson, J.A.L., Wiseman, R.W., Westerhoff, H.V. and Kushmerick, M.J. (1996) J. Biol. Chem. 271, 27995-279981, but the molecular mechanism of signal transduction remained unclear. Previously we described inhibition of cytochrome c oxidase by intramitochondrial ATP, accompanied by a change of hyperbolic into sigmoidal kinetics. The present study describes a sigmoidal relationship also between the ascorbate respiration of reconstituted cytochrome c oxidase and intraliposomal ADP concentration. Its possible role in the control of oxidative phosphorylation and cell respiration is discussed. PMID- 9989585 TI - Interaction between class B beta-lactamases and suicide substrates of active-site serine beta-lactamases. AB - The most widely used inactivators of active-site serine beta-lactamases behave as substrates of four class B metallo-beta-lactamases, but the efficiency of the catalytic process can vary by several orders of magnitude. A comparison of the kinetic parameters for the alpha and beta isomers of 6-iodopenicillanic acid shows that there is no general preference for the alpha isomer and that the efficient hydrolysis of imipenem by these enzymes must rest on other factors. PMID- 9989586 TI - Single-chain variable fragments selected on the 57-76 p21Ras neutralising epitope from phage antibody libraries recognise the parental protein. AB - Phage antibodies have been widely prospected as an alternative to the use of monoclonal antibodies prepared by traditional means. Many monoclonal antibodies prepared against peptides are able to recognise the native proteins from which they were derived. Here we show that the same is also true for phage antibodies. We have selected a number of single-chain variable fragments (scFv) from a large phage scFv library against a peptide from the switch region II of p21Ras. This peptide is known to reside in a mobile area of the native protein and is the epitope of a well characterised monoclonal antibody. Selected scFvs were able to recognise native p21Ras in both ELISA and Western blots, indicating that peptides are also likely to be very useful in selecting from phage antibody libraries. PMID- 9989587 TI - Irreversible conversion of xanthine dehydrogenase into xanthine oxidase by a mitochondrial protease. AB - Irreversible conversion of xanthine dehydrogenase (XDH) to its oxygen free radical producing oxidase (XO) form occurs through an uncharacterized proteolytic process, which was studied in human liver. Upon incubation of fresh unfrozen liver cytosol, XDH remained intact. When recombinant human XDH was coincubated with subcellular fractions of human liver, the mitochondrial intermembrane space was shown to contain a heat-labile activity that converted XDH irreversibly to XO. This activity is resistant to inhibitors of all major groups of proteases. We postulate that this novel type of proteolytic enzyme is released into the cytosol upon mitochondrial damage. PMID- 9989588 TI - Structure to 1.9 A resolution of a complex with herpes simplex virus type-1 thymidine kinase of a novel, non-substrate inhibitor: X-ray crystallographic comparison with binding of aciclovir. AB - Treatment of herpes infections with nucleoside analogues requires as an initial step the activation of the compounds by thymidine kinase. As an aid to developing more effective chemotherapy, both for treatment of recurrent herpes infection and in gene therapy systems where thymidine kinase is expressed, two high-resolution X-ray structures of thymidine kinase have been compared: one with the relatively poor substrate aciclovir (Zovirax), the other with a synthetic inhibitor having an N2-substituted guanine. Both compounds have similar binding modes in spite of their size difference and apparently distinct ligand properties. PMID- 9989589 TI - p42-MAP kinase is activated in EGF-stimulated interphase but not in metaphase arrested HeLa cells. AB - It is known that cellular signals produced in response to an inappropriate spindle formation cause the cell to be arrested at metaphase (M) in the cell cycle. We report here that the 42-kDa isoform of MAPK (ERK2) was tyrosyl phosphorylated and activated in response to epidermal growth factor (EGF) in interphase but not in M-arrested HeLa cells. However, the basal level of activity of M-arrested cells was higher than that of interphase, although the overall tyrosyl phosphorylation content was small. Further, the EGF receptor and its associated proteins GTPase-activating protein and phospholipase C were phosphorylated in M-arrested cells to a lower extent than they were in interphase. This implies that in spite of its high level of basal activity, the scarcity of MAPK activation in mitosis in response to EGF stems from an early impairment of phosphorylation of the receptor and neighboring proteins. The biological significance of these results underlies the importance of keeping the cell sheltered from extracellular signals when it undergoes division. PMID- 9989590 TI - Classical late infantile neuronal ceroid lipofuscinosis fibroblasts are deficient in lysosomal tripeptidyl peptidase I. AB - Tripeptidyl peptidase I (TPP-I) is a lysosomal enzyme that cleaves tripeptides from the N-terminus of polypeptides. A comparison of TPP-I amino acid sequences with sequences derived from an EST database suggested that TPP-I is identical to a pepstatin-insensitive carboxyl proteinase of unknown specificity which is mutated in classical late infantile neuronal ceroid lipofuscinosis (LINCL), a lysosomal storage disease. Both TPP-I and the carboxyl proteinase have an M(r) of about 46 kDa and are, or are predicted to be, resistant to inhibitors of the four major classes of proteinases. Fibroblasts from LINCL patients have less than 5% of the normal TPP-I activity. The activities of other lysosomal enzymes, including proteinases, are in the normal range. LINCL fibroblasts are also defective at degrading short polypeptides and this defect can be induced in normal fibroblasts by treatment with a specific inhibitor or TPP-I. These results suggest that the cell damage, especially neuronal, observed in LINCL results from the defective degradation and consequent lysosomal storage of small peptides. PMID- 9989591 TI - Proton gradient-induced changes of the interaction between CF0 and CF1 related to activation of the chloroplast ATP synthase. AB - Thylakoid energization by light causes destabilization of CF0CF1 so that the peripheral CF1 sector is more readily detached from the membrane by intermediate concentrations of the chaotropic salt NaSCN. Here we have investigated the correlation between the proton gradient-induced change of CF0CF1 interaction and CF0CF1 activation. The results indicate a close relationship between the two phenomena. The effect is most probably due to reduction of the electrostatic interaction between the two subcomplexes CF0 and CF1 as a consequence of protonations in the interface region. PMID- 9989592 TI - The lipopolysaccharide-binding protein participating in hemocyte nodule formation in the silkworm Bombyx mori is a novel member of the C-type lectin superfamily with two different tandem carbohydrate-recognition domains. AB - We recently isolated and characterized the lipopolysaccharide (LPS)-binding protein, BmLBP, from the larval hemolymph of the silkworm Bombyx mori. BmLBP is a pattern recognition molecule that recognizes the lipid A portion of LPS and participates in a cellular defense reaction. This paper describes the cDNA cloning of BmLBP. The deduced amino acid sequence of BmLBP revealed that BmLBP is a novel member of the C-type lectin superfamily with a unique structural feature that consists of two different carbohydrate-recognition domains in tandem, a short and a long form. PMID- 9989593 TI - Purification and characterization of hydrogenase from the marine green alga, Chlorococcum littorale. AB - Hydrogenase from the marine green alga, Chlorococcum littorale, was purified 1485 fold, resulting in a specific activity for hydrogen evolution of 75.7 micromol/min/mg of protein at 25 degrees C, using reduced methyl viologen as an electron donor. The K(m) value for methyl viologen was 0.5 mM. The purity of the enzyme was judged by native PAGE. The molecular weight was estimated to be 55 kDa by SDS-PAGE, and 57 kDa by gel filtration. The optimum temperature and pH value for hydrogen evolution were 50 degrees C and 7.5, respectively. The partially purified hydrogenase catalyzed hydrogen evolution from ferredoxin that had been isolated from the same cells, but not from NADH or NADPH. The K(m) value for ferredoxin was 0.68 microM. The enzyme was extremely oxygen sensitive, losing over 95% of its activity upon exposure to air within minutes, even at 4 degrees C. Two peptide fragments were obtained from the hydrogenase protein digested enzymatically, and their amino acid sequences were determined. No significant homology was found to any other known sequences of hydrogenases. PMID- 9989594 TI - A comparative study of two retaining enzymes of Trichoderma reesei: transglycosylation of oligosaccharides catalysed by the cellobiohydrolase I, Cel7A, and the beta-mannanase, Man5A. AB - HPLC, MALDI-TOF MS and NMR spectroscopy were used to investigate the hydrolysis of cello- and mannooligosaccharides by Cel7A and Man5A from Trichoderma reesei. The experimental progress curves were analysed by fitting the numerically integrated kinetic equations, which provided cleavage patterns for oligosaccharides. This data evaluation procedure accounts for product inhibition and avoids the initial slope approximation. In addition, a transglycosylation step had to be included in the model to reproduce the experimental progress curves. For the hydrolysis of manno-oligosaccharides, Man4-6, by Man5A no mannose was detected at the beginning of the reaction showing that only the internal linkages are hydrolysed. For cellotriose and cellotetraose hydrolysis by Cel7A, the main product is cellobiose and glucose is released from the non-reducing end of the substrate. Intermediary products longer than the substrates were detected by MALDI-TOF MS when oligosaccharides (Glc4-6 or Man4-6) were hydrolysed by either Cel7A or Man5A. Interestingly, two distinct transglycosylation pathways could be observed. Cel7A produced intermediates that are one unit longer than the substrate, whereas Man5A produced intermediates that are two units longer than the substrate. PMID- 9989595 TI - Physiological production of singlet molecular oxygen in the myeloperoxidase-H2O2 chloride system. AB - The putative role of singlet oxygen (1O2) in the respiratory burst of neutrophils has remained elusive due to the lack of reliable means to study its quantitative production. To measure 1O2 directly from biological or chemical reactions in the near infrared region, we have developed a highly sensitive detection system which employs two InGaAs/InP pin photodiodes incorporated with a dual charge integrating amplifier circuit. Using this detection system, we detected light emission derived from a myeloperoxidase (MPO)-mediated reaction in physiological conditions: pH 7.4, 1-30 nM MPO, 10-100 microM H2O2 and 100-130 mM CI in place of Br without the use of deuterium oxide. The MNPO-H2O2-CI(-) system exhibited a single emission peak at 1.27 microm with a spectral distribution identical to that of delta singlet oxygen. Our results suggest physiological production of 1O2 in the MPO-H2O2-CI(-) system at an intravacuolar neutral pH. The MPO-mediated generation of 1O2, which may have an important role in host defense mechanisms, is discussed in connection with previous results. PMID- 9989596 TI - Differential sensitivities of primary and secondary T cell responses to antigen structure. AB - Here we examined T cell responses to two analogs of a chimeric peptide encoding a known B and a known T cell epitope. In one of the analogs, the B cell epitope existed in a random conformation whereas it was restricted within a disulfide bonded cyclic loop in the other. Immunization of these peptides in mice revealed that the latter peptide was significantly poorer at priming T cells and our preliminary results suggest this could be the result of differential processing of the two analogs. While primary T cell responses were sensitive to the influence of conformation, secondary responses were not discriminatory for the two antigens confirming the differences in activation requirements for primary and secondary T cell responses. Further, our studies also suggest that the priming efficacy of a T cell epitope is influenced by its structural environment. PMID- 9989597 TI - Determinants of plasma coenzyme Q10 in humans. AB - In the present study, we assessed the strongest determinants of plasma coenzyme Q10 (Qm10) in 518 men and women (aged 45-70 years) with a stepwise multivariate regression model. Male gender (P<0.001), serum cholesterol (P<0.001), serum gamma glutamyltransferase (P<0.001), serum triglycerides (P< 0.001), age (P=0.017) and 4-day alcohol consumption (P=0.03) were the most important factors which were directly associated with plasma Q10). The intensity of conditioning exercise (P=0.03) and use of statins (P<0.05) showed an inverse association with plasma Q10. None of the assessed nutrients increased plasma Q10 levels significantly. Our results suggest that many confounding factors, in addition to serum cholesterol and triglycerides, should be taken into account when the role of plasma Q10 is examined in epidemiological research. PMID- 9989598 TI - Chaperone-assisted expression of authentic bovine adrenodoxin reductase in Escherichia coli. AB - Adrenodoxin reductase is an essential component of the mitochondrial monooxygenase systems that are involved in the synthesis of steroid hormones and related compounds. After removing by mutagenesis a secondary ribosome binding site and an mRNA loop formed between the gene and the vector, large amounts of the enzyme could be produced in Escherichia coli by coexpression with the HSP60 chaperone system. The purified protein was homogeneous enough for reproducible crystallization. The crystals diffracted X-rays isotropically beyond 1.7 A resolution permitting a structure analysis. PMID- 9989599 TI - Human thymidine kinase 2: molecular cloning and characterisation of the enzyme activity with antiviral and cytostatic nucleoside substrates. AB - Based on amino acid sequence information from purified mitochondrial thymidine kinase (TK2), a cDNA of 1930 bp was cloned, containing an open reading frame encoding 232 amino acid residues starting with the N-terminal sequence determined from the native human protein preparation. Northern blot analysis with the cDNA coding region demonstrated several TK2 mRNAs, with 2 and 4 kb forms present in many tissues. We also characterised N-terminally truncated (starting at position 18) human TK2 with pharmacologically important antiviral and cytostatic nucleoside analogues. Results were highly similar to those with the native TK2 preparation. The anti-leukaemic drug arabinosyl cytosine is phosphorylated. The antitumour drug difluorodeoxycytidine and its metabolite difluorodeoxyuridine are good substrates, with K(m) values of 66 and 29 microM, respectively, and a relative Vmax of 0.6 compared to that of thymidine. Negative cooperativity was found with thymidine and the anti-HIV drug 3'-azidothymidine, but the reaction followed Michaelis-Menten kinetics with deoxycytidine, arabinosyl cytosine, and arabinosyl thymine. The results demonstrate a broad substrate specificity and complex kinetics, and suggest a role for TK2 in the activation of chemotherapeutic nucleoside analogues. PMID- 9989600 TI - Aah VI, a novel, N-glycosylated anti-insect toxin from Androctonus australis hector scorpion venom: isolation, characterisation, and glycan structure determination. AB - Aah VI was isolated from the venom of the North African scorpion, Androctonus australis hector. It is the first glycosylated neurotoxin from scorpion venom to be described. It was not toxic to mice, when injected intracerebroventricularly at a dose of 1.2 microg per animal. However, it had typical activity in Blatella germanica cockroaches resulting in gradual paralysis and very low toxicity (LD50 = 8.5 microg/g of animal). It consists of 66 amino acid residues and is heterogeneously N-glycosylated at a single site, on asparagine 9, of the Asn-Gly Thr sequence. The potential N-glycosylation site was deduced from automatic Edman degradation and amino acid analysis, and glycan heterogeneity was evidenced by ESMS. Determination of the N-glycan structures (dHex, Hex and HexNAc) was assessed by nanoESMS/MS with picomolar amounts of sample. Current knowledge of N glycan structure and composition suggests that the glycan structures are derived from a common core. PMID- 9989601 TI - Proteasome inhibitors induce mitochondria-independent apoptosis in human glioma cells. AB - The proteasome inhibitors lactacystin and AcLLNal induced p53-independent apoptosis in two human glioma cell lines, and the apoptosis was accompanied by up regulation of immunoreactive wild-type p53, p21Waf1, Mdm2, and p27Kip1. Pretreatment with cycloheximide decreased the induction of cell death independently of p53 protein status, suggesting that the up-regulation of short lived proteins is associated with proteasome inhibitor-induced apoptosis. Caspase 3-like proteases were activated in the proteasome inhibitor-mediated apoptosis, and the induction of cell death was inhibited more effectively in the presence of z-VAD.fmk than in the presence of Ac-DEVD.fmk, suggesting that caspases other than caspase-3 are involved. Nonetheless, there were no significant alterations in levels of immunoreactive Bcl-2, Bcl-X(L), Bax, Bad, and Bak, nor any evidence of cytochrome c release into cytosol and dissipation of delta(psi)m. Thus, the proteasome inhibitor-induced apoptosis is mediated by a mitochondria-independent mechanism, and the once activated caspase-3 does not cause the cytochrome c release and the delta(psi)m disruption. PMID- 9989602 TI - HIV-1 gp160 decreases the K+ voltage-gated current from Jurkat E6.1 T cells by up phosphorylation. AB - HIV-1 gp120/gp160 is known to disturb the activity of p56lck, protein kinase C (PKC) and Ca2+ homeostasis in T lymphocytes. We found that gp160 decreases the Kv1.3 current of Jurkat E6.1 cells probably by increasing the PKC-dependent phosphorylation of Kv channel protein after 5 days. This decrease is dose dependent. In contrast, gp160 did not decrease the Kv1.3 current of the JCaM1.6 cell line, a p56(lck)-defective Jurkat cell line. This shows that p56lck was at the beginning of the events which induced the Kv1.3 current decrease. As a consequence of this decrease, Jurkat E6.1 cells were depolarized and exhibited a volume increase. PMID- 9989603 TI - pH-dependent thermal transitions of lentil lectin. AB - The thermal stability of lentil lectin in the 5.0-10.0 pH range was studied by high-sensitivity differential scanning calorimetry and infrared spectroscopy. The thermally induced transitions for protein were irreversible and strongly dependent upon the scan rate at all pH values, suggesting that the denaturation is under kinetic control. It is shown that process of lentil lectin denaturation can be interpreted with sufficient accuracy in terms of the simple kinetic scheme, N-->D, where k is a first-order kinetic constant that changes with temperature, as given by the Arrhenius equation, N is the native state, and D is the denatured state. On the basis of this model, the parameters of the Arrhenius equation were calculated. PMID- 9989604 TI - Arfaptin 1, an ARF-binding protein, inhibits phospholipase D and endoplasmic reticulum/Golgi protein transport. AB - Class I ADP-ribosylation factors (ARFs) are essential for coatomer and clathrin coat assembly and vesicular transport in the Golgi apparatus. However, little is known about the in vivo regulation of ARF actions. Recently we cloned arfaptin 1, a 39 kDa protein that binds active, GTPgammaS-liganded ARF and translocates with it to Golgi membranes. Here we show that phorbol ester-stimulated phospholipase D (PLD) activity is inhibited in arfaptin 1-overexpressing NIH 3T3 cells and that arfaptin 1 inhibits ARF activation of Golgi-associated PLD. Since PLD activity is thought to play a role in regulating vesicular transport in the secretory pathway, we determined the rate of glycosylation of vesicular stomatitis virus glycoprotein as a measure of protein transport from the endoplasmic reticulum through the Golgi apparatus. Arfaptin 1 overexpression was found to decrease the rate of this reaction approximately two-fold. These data suggest that arfaptin 1 is a regulator of ARF action in the Golgi apparatus. PMID- 9989605 TI - Alfalfa contains substantial 9-hydroperoxide lyase activity and a 3Z:2E-enal isomerase. AB - Fatty acid hydroperoxides formed by lipoxygenase can be cleaved by hydroperoxide lyase resulting in the formation of short-chain aldehydes and omega-oxo acids. Plant hydroperoxide lyases use 13- or 9-hydroperoxy linoleic and linolenic acid as substrates. Alfalfa (Medicago sativa L.) has been reported to contain a hydroperoxide lyase specific for 13-hydroperoxy linoleic and linolenic acid only. However, in addition to 13-hydroperoxide lyase activity we found substantial 9 hydroperoxide lyase activity in alfalfa seedlings as well. The specific activity for 9-hydroperoxy fatty acids was about 50% of the activity for the 13-isomers. Furthermore, alfalfa seedlings contain a 3Z:2E-enal isomerase that converts the 3Z-enal products to their 2E-enal isoforms. PMID- 9989606 TI - The N54 mutant of Galphas has a conditional dominant negative phenotype which suppresses hormone-stimulated but not basal cAMP levels. AB - The phenotype of a Ser to Asn mutation at position 54 of the alpha subunit of G(s)(N54-alpha(s)) was characterized in transient transfection experiments in COS and HEK293 cells. Expression of either wild type or N54-alpha(s) increased basal cAMP levels. In contrast, expression of wild type alpha(s), potentiated agonist stimulated cAMP levels, while expression of N54-alpha(s)caused a decrease. Thus, the N54-alpha(s) mutant possesses a conditional dominant negative phenotype, suppressing preferentially hormone-stimulated effects. PMID- 9989607 TI - Cleavage experiments with deoxythymidine 3',5'-bis-(p-nitrophenyl phosphate) suggest that the homing endonuclease I-PpoI follows the same mechanism of phosphodiester bond hydrolysis as the non-specific Serratia nuclease. AB - We show here that two nucleases, Serratia nuclease and I-PpoI, with contrasting specificities, i.e. non-specific vs. highly sequence specific, share a structurally similar active site region with conservation of the catalytically relevant histidine and asparagine residues. On the basis of a comparison of the available structures and biochemical data for wild type and mutant variants of Serratia nuclease and I-PpoI we propose that both enzymes have a common catalytic mechanism, a proposition that is supported by our finding that both enzymes accept deoxythymidine 3',5'-bis-(p-nitrophenyl phosphate) as a substrate and cleave it in an identical manner. According to this mechanism a histidine residue functions as a general base and Mg2+ bound to an asparagine residue as a Lewis acid in phosphodiester bond cleavage. PMID- 9989608 TI - Artificial chaperoning of insulin, human carbonic anhydrase and hen egg lysozyme using linear dextrin chains--a sweet route to the native state of globular proteins. AB - Linear dextrins (alpha-1,4-D-glucopyranoside chains) are known to possess amphiphilic surfaces and solubilize lipophilic compounds. We have assessed the ability of this amphiphilic surface of dextrin to inhibit the self-aggregation and assist the refolding of proteins. Addition of decameric dextrin, or dextrin 10, in the renaturation buffer improves the refolding yield of human carbonic anhydrase from its guanidinium chloride-induced denatured state. It is also seen to inhibit the self-aggregation of insulin. The ability of dextrin-10 to interact with cetyltrimethylammonium bromide and postpone its critical micellar concentration allows the use of dextrin-10 as a 'detergent stripping agent' in a novel artificial chaperoning process described earlier. The aggregation of human carbonic anhydrase and lysozyme upon refolding is prevented by cetyltrimethylammonium bromide due to the formation of a protein-detergent complex; dextrin-10 strips off the detergent from the complex and allow the proteins to fold, thus increasing the renaturation yield. Dextran-4 (the alpha 1,6-D-glucopyranoside chain), which does not exhibit amphiphilic properties, does not help in such artificial chaperoning. PMID- 9989609 TI - Programming of enzyme specificity by substrate mimetics: investigations on the Glu-specific V8 protease reveals a novel general principle of biocatalysis. AB - In this paper the universal validity of the substrate mimetic concept in enzymatic C-N ligations was expanded to anionic leaving groups based on the specificity determinants of Glu-specific endopeptidase from Staphylococcus aureus (V8 protease). In an empirical way a specific mimetic moiety was designed from simple structure-function relationship studies. The general function of the newly developed substrate mimetics to serve as an artificial recognition site for V8 protease have been examined by hydrolysis kinetic studies. Enzymatic peptide syntheses qualify the strategy of substrate mimetics as a powerful concept for programming the enzyme specificity in the direction of a more universal application of enzymes in the general area of biocatalysis. PMID- 9989610 TI - Role of the C-terminal domain of Bax and Bcl-XL in their localization and function in yeast cells. AB - It has been suggested that the C-terminal domain of Bcl-2 family members may contain a signal anchor sequence that targets these proteins to the mitochondrial outer membrane. We have investigated the consequence of deleting this domain upon cytochrome c release in yeast strains that coexpress truncated forms of Bax (i.e. BaxA) and Bcl-X(L) (i.e. Bcl-X(L)delta). We find that (i) Bax(delta) is as efficient as full-length Bax in promoting cytochrome c release, but Bcl-x(L)delta has remarkably reduced rescuing ability compared to full-length Bcl-x(L); (ii) full-length Bcl-X(L) protein acts by relocalizing Bax from the mitochondrial fraction to the soluble cytosolic fraction; (iii) Bax undergoes N-terminal cleavage when expressed in yeast, which is prevented by coexpression of Bcl-X(L), suggesting that Bcl-x(L) may mask the cleavage site of Bax through a direct physical interaction of the two proteins. PMID- 9989611 TI - Studies of the reactivity of artificial peroxidase-like hemoproteins based on antibodies elicited against a specifically designed ortho-carboxy substituted tetraarylporphyrin. AB - The temperature and pH dependence as well as the selectivity of the peroxidase activity of a complex associating a monoclonal antibody 13G10 with its iron(III) alpha,alpha,alpha,beta-mesotetrakis(ortho-carboxyphenyl) porphyrin (Fe(ToCPP)) hapten have been studied and compared to those of Fe(ToCPP) alone. It first appears that the peroxidase activity of the 13G10-Fe(ToCPP) complex is remarkably thermostable and remains about 5 times higher than that of Fe(ToCPP) alone until at least 80 degrees C. Secondly, this complex is able to use not only H2O2 as oxidant but also a wide range of hydroperoxides such as alkyl, aralkyl and fatty acid hydroperoxides and catalyze their reduction 2-6-fold faster than Fe(ToCPP) alone. It is also able to catalyze the oxidation by H202 of a variety of reducing cosubstrates such as 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), o-phenylenediamine (OPD), 3,3',5,5'-tetramethylbenzidine (TMB) and 3,3' dimethoxybenzidine 3-8-fold faster than Fe(ToCPP) alone, the bicyclic aromatic ABTS and TMB being the best reducing cosubstrates. Finally, a pH dependence study, between pH 4.6 and 7.5, of the oxidation of ABTS by H2O2 in the presence of either 13G10-Fe(ToCPP) or Fe(ToCPP) shows that Km(H2O2) values vary very similarly for both catalysts, whereas very different variations are found for the k(cat) values. With Fe(ToCPP) as catalyst the k(cat) value remains constant around 100 min(-1) whereas with the 13G10-Fe(ToCPP) complex, it increases sharply below pH 5 to reach 540 min -1 at pH 4.6. This could be due to the participation of a carboxylic acid side chain of the antibody protein, as a general acid-base catalyst, to the heterolytic cleavage of the O-O bond of H2O2 leading to the highly reactive iron(V)-oxo intermediate in the peroxidase mechanism. Accordingly, the modification of the carboxylic acid residues of antibody 13G10 by glycinamide leads to a 50% decrease of the peroxidase activity of the 13G10 Fe(ToCPP) complex. PMID- 9989612 TI - Apocynin increases glutathione synthesis and activates AP-1 in alveolar epithelial cells. AB - Apocynin (4-hydroxy-3-methoxy-acetophenone) is a potent intracellular inhibitor of superoxide anion production in neutrophils. In this study, we studied the effect of apocynin on the regulation of the antioxidant glutathione (GSH) and activation of the transcription factor AP-I in human alveolar epithelial cells (A549). Apocynin enhanced intracellular GSH by increasing gamma-glutamylcysteine synthetase activity in A549 cells. Apocynin also increased the expression of gamma-GCS heavy subunit mRNA. This was associated with increased AP-1 DNA binding as measured by the electrophoretic mobility shift assay. These data indicate that apocynin displays antioxidant properties, in part, by increasing glutathione synthesis through activation of AP-1. PMID- 9989614 TI - Autoimmunity in paraneoplastic neurological syndromes: closer to the truth? PMID- 9989613 TI - Cortin disaster: lissencephaly genes spell double trouble for the developing brain. PMID- 9989615 TI - Characterization of mutations in the gene doublecortin in patients with double cortex syndrome. AB - Mutations in the X-linked gene doublecortin, which encodes a protein with no dear structural homologues, are found in pedigrees in which affected females show "double cortex" syndrome (DC; also known as subcortical band heterotopia or laminar heterotopia) and affected males show X-linked lissencephaly. Mutations in doublecortin also cause sporadic DC in females. To determine the incidence of doublecortin mutations in DC, we investigated a cohort of eight pedigrees and 47 sporadic patients with DC for mutations in the doublecortin open reading frame as assessed by single-stranded conformational polymorphism analysis. Mutations were identified in each of the eight DC pedigrees (100%), and in 18 of the 47 sporadic DC patients (38%). Identified mutations were of two types, protein truncation mutations and single amino acid substitution mutations. However, pedigrees with DC displayed almost exclusively single amino acid substitution mutations, suggesting that patients with these mutations may have less of a reproductive disadvantage versus those patients with protein truncation mutations. Single amino acid substitution mutations were tightly clustered in two regions of the open reading frame, suggesting that these two regions are critical for the function of the Doublecortin protein. PMID- 9989616 TI - Intracellular levels of the LIS1 protein correlate with clinical and neuroradiological findings in patients with classical lissencephaly. AB - We report on the genotype-phenotype correlation in 7 patients with classical lissencephaly carrying a heterozygous subtle mutation in the LIS1 gene. Six patients, showed a mutation predicted to encode for a truncated protein, and one mutation altered a splicing site, resulting in skipping of exon 4. Western blot analysis performed on the lymphoblastoid cell line of 2 patients bearing truncating mutations indicated that the mutated allele did not produce a detectable amount of the LIS1 protein; whereas the analysis performed on the fibroblasts from the patient with a splice-site mutation was suggestive of partial protein synthesis from the mutated allele. Although clinical and magnetic resonance imaging findings of patients with truncating mutations did not differ from those observed in patients with a heterozygous deletion, the patient bearing the exon-skipping mutation had less severe clinical and brain involvement. Our data suggest that truncating mutations in the LIS1 gene are relatively common among patients with classical lissencephaly not bearing a heterozygous deletion at 17p13.3, and strengthen the relevance of correct intracellular dosage of the LIS1 protein in the neuronal migration process. PMID- 9989617 TI - Cell-mediated autoimmunity in paraneoplastic neurological syndromes with anti-Hu antibodies. AB - Paraneoplastic encephalomyelitis or subacute sensory neuronopathy associated with small-cell lung cancer (SCLC) and high titers of anti-HuD antibodies, also called the "anti-Hu syndrome," is believed to result from an immune response triggered by tumor antigens and misdirected to the neurons. To further assess the issue of cell-mediated immunity in this disease, the peripheral blood lymphocyte surface phenotype was studied in 15 patients suffering from the anti-Hu syndrome (seropositive group) and in two control groups consisting of 12 seronegative SCLC patients without neurological syndrome and 15 healthy volunteers. In addition, the recombinant human HuD protein was used to stimulate in vitro peripheral blood mononuclear cells of 10 seropositive patients and of 10 patients from each control group. Phenotypic analysis of the peripheral blood lymphocytes revealed a significant increase of the memory helper (CD45RO+CD4+) T cells in the seropositive group in comparison with the two control groups. Antigen-specific proliferation of peripheral blood mononuclear cells, measured by [3H]thymidine uptake after HuD antigen stimulation, was much higher in the seropositive group than in the two control groups, and phenotypic analysis of proliferating cells revealed a significant expansion of the CD45RO subpopulation of T cells in the seropositive group. Furthermore, after HuD stimulation, a significant increase of the interferon-gamma/interleukin-4 ratio was found in culture supernatants of the seropositive group compared with seronegative SCLC patients and normal controls. Taken together, these results indicate that HuD protein is an antigenic target for autoreactive CD4+ T cells, presumably of the Th1 subtype, which could therefore be directly involved in cell-mediated injury of the nervous system as well as in antitumoral immunity. PMID- 9989618 TI - Anti-GD1a antibody is associated with axonal but not demyelinating forms of Guillain-Barre syndrome. AB - Immunopathological studies suggest that the target of immune attack is different in the subtypes of Guillain-Barre syndrome (GBS). In acute motor axonal neuropathy (AMAN), the attack appears directed against the axolemma and nodes of Ranvier. In acute inflammatory demyelinating polyneuropathy (AIDP), the attack appears directed against a component of the Schwann cell. However, the nature of the antigenic targets is still not clear. We prospectively studied 138 Chinese GBS patients and found that IgG anti-GD1a antibodies were closely associated with AMAN but not AIDP. With a cutoff titer of greater than 1:100, 60% of AMAN versus 4% of AIDP patients had IgG anti-GD1a antibodies; with a cutoff titer of greater than 1:1,000, 24% of AMAN patients and none of the AIDP patients had IgG anti GD1a antibodies. In contrast, low levels of IgG anti-GM1 antibodies (> 1:100) were detected in both the AMAN and the AIDP forms (57% vs 35%, NS). High titers of IgG anti-GM1 (>1:1,000) were more common in the AMAN form (24% vs 8%, NS). Serological evidence of recent Campylobacter infection was detected in 81% of AMAN and 50% of AIDP patients, and anti-ganglioside antibodies were common in both Campylobacter-infected and noninfected patients. Our results suggest that IgG anti-GD1a antibodies may be involved in the pathogenesis of AMAN. PMID- 9989619 TI - Predominance of neuronal mRNAs in individual Alzheimer's disease senile plaques. AB - The sequestration of RNA in Alzheimer's disease (AD) senile plaques (SPs) and the production of intraneuronal amyloid-beta peptides (Abeta) prompted analysis of the mRNA profile in single immunocytochemically identified SPs in sections of AD hippocampus. By using amplified RNA expression profiling, polymerase chain reaction, and in situ hybridization, we assessed the presence and abundance of 51 mRNAs that encode proteins implicated in the pathogenesis of AD. The mRNAs in SPs were compared with those in individual CA1 neurons and the surrounding neuropil of control subjects. The remarkable demonstration here, that neuronal mRNAs predominate in SPs, implies that these mRNAs are nonproteinaceous components of SPs, and, moreover, that mRNAs may interact with Abeta protein and that SPs form at sites where neurons degenerate in the AD brain. PMID- 9989620 TI - Autosomal dominant lateral temporal epilepsy: clinical and genetic study of a large Basque pedigree linked to chromosome 10q. AB - We report a large family with a temporal partial epilepsy syndrome inherited in an autosomal dominant mode, with a penetrance of about 80%. This epilepsy syndrome is benign, with age of onset in the second or third decade of life. It is characterized by rare partial seizures, usually secondarily generalized, arising mostly during sleep, without postictal confusion. There is a good response to the antiepileptic therapy but often a recurrence of seizures after drug withdrawal. The partial component, visual (lights, colors, and simple figures) or auditory (buzzing or "humming like a machine"), the existence of temporo-occipital interictal electroencephalographic epileptiform abnormalities, and the hypoperfusion in the temporal lobe detected by interictal hexamethylpropyleneamine oxime-technetium 99m (HMPAO-Tc99m) single-photon emission computed tomography, strongly suggest a lateral temporal lobe origin. The genetic analysis found linkage to chromosome 10q, and localized a gene in a 15-cM interval that overlaps a previously found localization for partial epilepsy in a large three-generation family. This syndrome could be called autosomal dominant lateral temporal epilepsy. PMID- 9989621 TI - Miller Fisher anti-GQ1b antibodies: alpha-latrotoxin-like effects on motor end plates. AB - In the Miller Fisher syndrome (MFS) variant of the Guillain-Barre syndrome, weakness is restricted to extraocular muscles and occasionally other craniobulbar muscles. Most MFS patients have serum antibodies against ganglioside type GQ1b of which the pathophysiological relevance is unclear. We examined the in vitro effects of MFS sera, MFS IgG, and a human monoclonal anti-GQ1b IgM antibody on mouse neuromuscular junctions (NMJs). It was found that anti-GQ1b antibodies bind at NMJs where they induce massive quantal release of acetylcholine from nerve terminals and eventually block neuromuscular transmission. This effect closely resembled the effect of the paralytic neurotoxin alpha-latrotoxin at the mouse NMJs, implying possible involvement of alpha-latrotoxin receptors or associated downstream pathways. By using complement-deficient sera, the effect of anti-GQ1b antibodies on NMJs was shown to be entirely dependent on activation of complement components. However, neither classical pathway activation nor the formation of membrane attack complex was required, indicating the effects could be due to involvement of the alternative pathway and intermediate complement cascade products. Our findings strongly suggest that anti-GQ1b antibodies in conjunction with activated complement components are the principal pathophysiological mediators of motor symptoms in MFS and that the NMJ is an important site of their action. PMID- 9989622 TI - Friedreich's ataxia: point mutations and clinical presentation of compound heterozygotes. AB - Friedreich's ataxia is the most common inherited ataxia. Ninety-six percent of patients are homozygous for GAA trinucleotide repeat expansions in the first intron of the frataxin gene. The remaining cases are compound heterozygotes for a GAA expansion and a frataxin point mutation. We report here the identification of 10 novel frataxin point mutations, and the detection of a previously described mutation (G130V) in two additional families. Most truncating mutations were in exon 1. All missense mutations were in the last three exons coding for the mature frataxin protein. The clinical features of 25 patients with identified frataxin point mutations were compared with those of 196 patients homozygous for the GAA expansion. A similar phenotype resulted from truncating mutations and from missense mutations in the carboxy-terminal half of mature frataxin, suggesting that they cause a comparable loss of function. In contrast, the only two missense mutations located in the amino-terminal half of mature frataxin (D122Y and G130V) cause an atypical and milder clinical presentation (early-onset spastic gait with slow disease progression, absence of dysarthria, retained or brisk tendon reflexes, and mild or no cerebellar ataxia), suggesting that they only partially affect frataxin function. The incidence of optic disk pallor was higher in compound heterozygotes than in expansion homozygotes, which might correlate with a very low residual level of normal frataxin produced from the expanded allele. PMID- 9989623 TI - Ensheathing glia transplants promote dorsal root regeneration and spinal reflex restitution after multiple lumbar rhizotomy. AB - Previously, we have shown that transplants of olfactory bulb ensheathing cells promoted regeneration of transected dorsal roots into the spinal cord. In this study, we assessed the ability of regenerating axons to make functional connections in the cord. Dorsal roots L3 to L6 were sectioned close to their entrance into the spinal cord and reapposed after injecting a suspension of ensheathing cells into each dorsal root entry zone (Group G). Afferent regeneration into the cord and recovery of spinal reflexes were compared with animals that received no injection (Group S) or culture medium without cells (Group C). Electrophysiological tests, to measure nerve conduction and spinal reflexes (H response and withdrawal reflex) evoked by stimulation of afferents of the sciatic nerve, were performed. At 14 days after surgery, H response was found in only 1 of 7 rats of Group G, and withdrawal reflexes were absent from all animals. At 60 days, the H response reappeared in 7 of 10 rats of Group G, and 1 of 5 of each of Groups C and S. The withdrawal reflex recovered in 4 of 10 rats of Group G, but in none of Groups C and S. Immunohistochemical labeling for calcitonin gene-related peptide (CGRP) in rats of Group G showed immunoreactive fibers entering the dorsal horn from sectioned roots, although at lower density than in the contralateral side. In conclusion, transplanted ensheathing cells promoted central regeneration and functional reconnection of regenerating sensory afferents. PMID- 9989624 TI - New insights into positional alcohol nystagmus using three-dimensional eye movement analysis. AB - The semicircular canals selectively transduce angular velocity and are normally insensitive to gravity and linear acceleration. In acute alcohol intoxication, however, the cupula becomes lighter than the endolymph, rendering it sensitive to gravity (buoyancy hypothesis). This results in positional alcohol nystagmus (PAN) and rotatory vertigo. We evaluated PAN in 8 normal subjects by means of three dimensional eye-movement analysis in an attempt to clarify if the buoyancy mechanism is sufficient to explain PAN. Forty minutes after intake of 0.8 g of alcohol/kg of body weight, the subjects were positioned such that the lateral canals were earth vertical. They were then rotated in the plane of the lateral canals about an earth-horizontal axis to either 45 degrees or 90 degrees , right or left ear down, and eye movements were recorded for 40 seconds in each position. The spatial analysis of the responses showed that in addition to the nystagmus induced by the buoyancy of all six cupulae, alcohol intoxication also causes a vertical velocity offset (in all subjects, slow phase down) that is independent of the orientation of the subject in space. The offset may represent a toxic effect on central vestibular pathways, producing a tone imbalance of the vertical vestibulo-ocular reflex. PMID- 9989625 TI - Early-onset myasthenia gravis: a recurring T-cell epitope in the adult-specific acetylcholine receptor epsilon subunit presented by the susceptibility allele HLA DR52a. AB - No immunodominant T-cell epitopes have yet been reported in the human acetylcholine receptor (AChR), the target of the pathogenic autoantibodies in myasthenia gravis (MG). We have selected and characterized T cells from MG patients by restimulation in culture with recombinant human AChR to alpha, gamma and epsilon subunits; the gamma and epsilon distinguish the fetal and adult AChR isoforms, respectively. We obtained clones specific for the epsilon, rather than the alpha or gamma, subunit in 3 of the first 4 early-onset MG cases tested. They all responded to peptide epsilon201-219 and to low concentrations of adult but not fetal AChR. Moreover, although using different T-cell receptor genes, they were all restricted to HLA-DR52a (DRB3*0101), a member of the strongly predisposing HLA-A1-B8-DR3 haplotype. This apparently immunodominant epsilon201 219 epitope (plus DR52a) was also recognized by clones from an elderly patient whose MG had recently been provoked by the drug D-penicillamine. In all 4 cases, however, the serum antibodies reacted better with fetal than adult AChR and may thus be end products of determinant spreading initiated by adult AChR-specific T cell responses. Furthermore, as these T cells had a pathogenic Th1 phenotype, with the potential to induce complement-activating antibodies, they should be important targets for selective immunotherapy. PMID- 9989626 TI - Expression of ataxin-2 in brains from normal individuals and patients with Alzheimer's disease and spinocerebellar ataxia 2. AB - Spinocerebellar ataxia type 2 (SCA2) is caused by expansion of a CAG trinucleotide repeat located in the coding region of the human SCA2 gene. The SCA2 gene product, ataxin-2, is a basic protein with two domains (Sm1 and Sm2) implicated in RNA splicing and protein interaction. However, the wild-type function of ataxin-2 is yet to be determined. To help clarify the function of ataxin-2, we produced antibodies to three antigenic peptides of ataxin-2 and analyzed the expression pattern of ataxin-2 in normal and SCA2 adult brains and cerebellum at different developmental stages. These studies revealed that (1) both wild-type and mutant forms of ataxin-2 were synthesized; (2) the wild-type ataxin-2 was localized in the cytoplasm in specific neuronal groups with strong labeling of Purkinje cells; (3) the level of ataxin-2 increased with age in Purkinje cells of normal individuals; and (4) ataxin-2-like immunoreactivity in SCA2 brain tissues was more intense than in normal brain tissues, and intranuclear ubiquitinated inclusions were not seen in SCA2 brain tissues. PMID- 9989627 TI - Evidence of a genetic factor in migraine with aura: a population-based Danish twin study. AB - We studied the genetic influence on cause of migraine with aura (MA) by analyzing a twin population. The twin sample consisted of 2,026 monozygotic (MZ) twins and 3,334 same-sex dizygotic (DZ) twins, born from 1953 to 1960, from the population based New Danish Twin Register. A validated questionnaire was used to screen for migraine, the response rate being 87%, and similar among MZ and DZ twins. All twin pairs with at least 1 twin with possible MA were interviewed by a physician experienced in headache diagnoses. The answers from the questionnaire as well as the zygosity of the twins were blinded for the interviewer. A total of 211 twin pairs were identified, of whom 77 pairs were MZ and 134 pairs were DZ. The lifetime prevalence of MA was 7% and with a male-to-female ratio of 1:1.1. The pairwise concordance rates were significantly higher in MZ (34%) than in DZ twin pairs (12%), emphasizing the importance of genetic factors in MA. However, environmental factors are also important, as the pairwise concordance rate was less than 100% in MZ twin pairs. The recurrence risk of MA was 50% in MZ and 21% in DZ twin pairs. In nontwin siblings, the recurrence risk of MA is 27%, which is similar to the recurrence risk in DZ twins. This indicates that MA is not developed due to specific environmental factors shared by the twins. PMID- 9989628 TI - Interferon-gamma secretion by peripheral blood T-cell subsets in multiple sclerosis: correlation with disease phase and interferon-beta therapy. AB - Interferon-gamma (IFN-gamma) is implicated as a participant in the immune effector and regulatory mechanisms considered to mediate the pathogenesis of multiple sclerosis (MS). We have used an intracellular cytokine staining technique to demonstrate that the proportion of ex vivo peripheral blood CD4 and CD8 T-cell subsets expressing IFN-gamma is increased in secondary progressing (SP) MS patients, whereas the values in untreated relapsing-remitting (RR) MS patients are reduced compared with those of controls. Patients treated with interferon-beta (IFN-beta) have an even more significant reduction in the percentage of IFN-gamma-secreting cells. The finding that the number of IFN-gamma expressing CD8 cells is increased in SPMS patients, a group with reduced functional suppressor activity, and is most significantly reduced by IFN-beta therapy, which increases suppressor activity, indicates that IFN-gamma secretion by CD8 T cells and functional suppressor defects attributed to this cell subset in MS can be dissociated. PMID- 9989629 TI - An association between autosomal dominant cerebral cavernomas and a distinctive hyperkeratotic cutaneous vascular malformation in 4 families. AB - Cerebral cavernomas (CCMs) are vascular malformations that may be inherited as an autosomal dominant condition for which a gene, CCM1, was mapped to chromosome 7. Poorly defined cutaneous malformations were sometimes described in association with CCMs. During a national survey, 57 French CCM families were studied. Co occurrence of CCMs and a distinctive cutaneous vascular malformation was observed in 4 families. Ten individuals belonging to these families showed similar hyperkeratotic cutaneous capillary venous malformations (HCCVMs). In 3 families, the histology showed orthokeratosis and hyperkeratosis as well as dilated capillaries in the dermis extending to the hypodermis and confirmed the diagnosis of HCCVM. Genetic analysis strongly supports linkage of these families to the CCM1 locus on chromosome 7. The HCCVM seems to be a peculiar cutaneous vascular malformation associated with CCMs. These data strongly suggest that HCCVMs and CCMs in these families are due to the same genetic abnormality. PMID- 9989630 TI - Epilepsia partialis continua: a new manifestation of anti-Hu-associated paraneoplastic encephalomyelitis. AB - We report on 3 anti-Hu-positive patients who presented with clinical and electroencephalographic (EEG) features of epilepsia partialis continua (EPC). Two of the patients had an associated small cell carcinoma. Magnetic resonance imaging (MRI) disclosed a hyperintense nonenhancing focal lesion in T2-weighted images in the sensorimotor area in 2 patients. Histopathological analysis of the lesion revealed inflammatory infiltrates and neuronal cell loss. In the patient who had a postmortem study, these neuropathological changes were not observed in other areas of the nervous system. This study emphasizes that the possibility of an anti-Hu-associated paraneoplastic disorder must be considered in patients with cortical encephalitis presenting with EPC when a brain tumor can be excluded. PMID- 9989631 TI - Epstein-Barr virus in monitoring the response to therapy of acquired immunodeficiency syndrome-related primary central nervous system lymphoma. AB - To evaluate the value of Epstein-Barr virus DNA (EBV-DNA) assay in cerebrospinal fluid (CSF) for monitoring the response to treatment in acquired immunodeficiency syndrome-related primary central nervous system lymphoma (AIDS-PCNSL), 9 human immunodeficiency virus-infected patients with biopsy-proven AIDS-PCNSL who underwent multimodal therapy were investigated for EBV-DNA detection in CSF by semiquantitative nested polymerase chain reaction (PCR). Tumoral tissue expression of bcl-6 oncogene protein and of EBV-encoded latent membrane protein (LMP-1) was also investigated. The 2 patients who had a response to chemotherapy showed a reduction of mean EBV-DNA concentration values after chemotherapy and displayed a large noncleaved morphology and a BCL-6+/LMP-1- phenotype. Conversely, the 4 patients with progressive disease after chemotherapy showed increasing mean values of EBV-DNA and displayed an immunoblastic morphology and a BCL-6-/LMP-1+ phenotype. No significant changes were observed for patients with stable disease. EBV-DNA burden reduction was significantly associated with prolonged survival. These results suggest that EBV-DNA monitoring might be helpful in predicting response to chemotherapy and in segregating distinct biological and prognostic categories of AIDS-PCNSL. PMID- 9989633 TI - Three-dimensional tracking of axonal projections in the brain by magnetic resonance imaging. AB - The relationship between brain structure and complex behavior is governed by large-scale neurocognitive networks. The availability of a noninvasive technique that can visualize the neuronal projections connecting the functional centers should therefore provide new keys to the understanding of brain function. By using high-resolution three-dimensional diffusion magnetic resonance imaging and a newly designed tracking approach, we show that neuronal pathways in the rat brain can be probed in situ. The results are validated through comparison with known anatomical locations of such fibers. PMID- 9989632 TI - Genetic locus heterogeneity in Lafora's progressive myoclonus epilepsy. AB - In 1995, we mapped a gene for Lafora's progressive myoclonus epilepsy in chromosome 6q23-25. In 1997 and 1998, we reduced the size of the locus to 300 kb, and an international collaboration identified mutations in the protein tyrosine phosphatase gene. Here, we examine for heterogeneity through the admixture test in 22 families and estimate the proportion of linked families to be 75 to 85%. Extremely low posterior probabilities of linkage (Wi), exclusionary LOD scores, and haplotypes identify 4 families unlikely to be linked to chromosome 6q24. PMID- 9989634 TI - Mutation in the tau exon 10 splice site region in familial frontotemporal dementia. PMID- 9989635 TI - Immunohistochemical detection of infected neurons as a rapid diagnosis of enterovirus 71 encephalomyelitis. PMID- 9989636 TI - Stimulating the phagocytes: progress and problems. PMID- 9989637 TI - Proposed new bacterial taxa and proposed changes of bacterial names published during 1997 and considered to be of interest to medical or veterinary bacteriology. AB - A list of names of bacteria published or validated in 1997 is presented. Comments are made of the tendency to base names of new taxa on a single bacterial strain and the consequences for reliable descriptions that this tendency implies. PMID- 9989638 TI - Surface protein p104 is involved in adhesion of Listeria monocytogenes to human intestinal cell line, Caco-2. AB - Adhesion of Listeria monocytogenes to intestinal endothelial cells is an important initial event in the pathogenesis of infection which is not well understood. The suggestion has been made that some proteins, including internalin and actin polymerisation protein (ActA), and carbohydrate molecules mediate, at least in part, the adhesion of listeria to certain cultured mammalian cells. This study investigated the role of a L. monocytogenes cell-surface protein of 104 kDa (p104) in adhesion to human intestinal enterocyte-like Caco-2 cell lines by transposon (Tn916) mutagenesis and a p104-specific monoclonal antibody (MAb-H7). Genotypic and phenotypic characteristics of Tn916-transformed L. monocytogenes strains, AAMU530 and AAMU572, revealed that these strains did not express p104, and the transposon had been inserted at a single locus in the structural gene. Strains AAMU530 and AAMU572 yielded only 10 and 6.3% adhesion to Caco-2 cells. Coating of L. monocytogenes and L. innocua wild-type strains with MAb-H7 reduced adhesion to Caco-2 cells from 100% to 50 and 45%, respectively, whereas on isotype control MAb EM-7G1 had no effect. Western blot analysis with MAb-H7 indicated that p104 is present in all Listeria spp. except in L. grayi. Furthermore, p104 is also present in internalin (BUG8) and ActA (LUT12) deficient strains, suggesting that p104 is indeed different from internalin or ActA proteins. Cytotoxicity analysis of strains AAMU530 and AAMU572 demonstrated that these strains, although haemolytic and phospholipase-positive, were avirulent when tested with a hybridoma B-lymphocyte cell line. Loss of virulence could be attributed to the interruption of adhesion of mutant strains to the hybridoma cell line. These results strongly suggest that p104 is an adhesion factor in L. monocytogenes and possibly in other Listeria species and is involved in adhesion to intestinal cells. PMID- 9989639 TI - Characterisation of dermonecrotic toxin-producing strains of Pasteurella multocida subsp. multocida isolated from man and swine. AB - Thirty-six isolates, from man or swine, of Pasteurella multocida subsp. multocida producing (n = 13) or not producing (n = 23) the dermonecrotic toxin (DNT) were studied by numerical analysis, capsular typing and ribotyping. Toxigenic strains were also characterised by restriction fragment length polymorphism (RFLP) of the toxA gene and pulsed-field gel electrophoresis (PFGE). Numerical analysis differentiated the Pasteurella species and subspecies, but did not discriminate between toxigenic and nontoxigenic strains. RFLP demonstrated that toxA was located in a conserved part of the chromosome of all toxigenic strains. Ribotyping provided evidence of a close association between DNT production and one of the six EcoRI ribotypes designated as E2. In contrast, PFGE provided evidence for significant DNA polymorphism amongst the toxigenic strains. Results of phenotypic and genotypic studies suggested that toxigenic strains do not form a clone within the subspecies multocida. No difference was found between toxigenic strains of porcine or human origin by biochemical characterisation, capsular serotyping or genomic typing methods. PMID- 9989640 TI - Isolation and characterisation of neurotoxigenic Clostridium butyricum from soil in China. AB - Soil specimens collected from a site around the home of patients with food-borne type E. botulism probably caused by neurotoxigenic Clostridium butyricum in Guanyun, Jiangsu province, China, were examined for the presence of neurotoxigenic C. butyricum. Five lakeside sites of Weishan lake, in an area near to the sites where the type E. botulism outbreaks caused by neurotoxigenic C. butyricum occurred were also surveyed. Type E toxin-producing C. butyricum was isolated from soil from four sites including the site in Guanyun. Polymerase chain reaction assay demonstrated the presence of the type E toxin gene in all the toxigenic isolates. The biochemical properties of the isolates from the Guanyun soil and the lakeside soil were identical except for inulin fermentation and starch hydrolysis properties. These results indicate that neurotoxigenic C. butyricum has its principal habitat in soil. PMID- 9989641 TI - Identification and characterisation of a cytotoxic porin-lipopolysaccharide complex from Campylobacter jejuni. AB - A clinical isolate of Campylobacter jejuni, previously found to produce a toxin active in cell culture assays, was used for identification and characterisation of a cytotoxic porin-lipopolysaccharide (LPS) complex. This cytotoxic complex was isolated by high-performance liquid chromatography of crude concentrated culture supernate and DEAE-anion exchange chromatography. The complex had a toxic activity of 20.1 tissue culture dose50 (TCD50)/microg of protein for HEp-2 cells, 7.49 TCD50/microg of protein for HeLa cells and 1.87 TCD50/microg of protein for Chinese hamster ovary cells. Analysis by SDS-PAGE revealed a single protein band of 45 kDa and a high mol. wt carbohydrate moiety. The complex gave a positive result in the Limulus amoebocyte lysate test, indicating that the co-purifying carbohydrate was LPS, and had specificity for the lectins Galanthus nivalis agglutinin, Maackia amurensis agglutinin and Datura stramonium agglutinin. The cytotoxic activity associated with the complex was heat-labile at 70 degrees C, resistant to inactivation with trypsin and retained activity after treatment with sodium metaperiodate and the glycosidases neuraminidase and N-glycosidase F. Sequencing of the N-terminus of the protein component of the complex revealed 97% homology with the major outer-membrane porin protein from C. jejuni. The cytotoxic activity of the complex was neutralised by a polyclonal, homologous antiserum, which reacted on Western blot with the 45-kDa protein, but not by polyclonal antisera raised against a number of other bacterial toxins. PMID- 9989642 TI - Response of gonococcal clinical isolates to acidic conditions. AB - This study examined the response to acidic conditions of four gonococcal isolates -NRL38874 (Proto/IB-2), NRL38884 (Pro/IA-2), NRL38953 (Proto/IB-3) and NRL39029 (Pro/IA-3) - obtained from various sites in patients in whom a diagnosis of pelvic inflammatory disease had been made by laparoscopic examination. Acid tolerance of the clinical isolates was strain and growth phase dependent. Growth of the four strains on solid media was undetectable below pH 5.8. In liquid culture, strain NRL38884 did not survive below pH 5.2; strains NRL38874, NRL38953 and NRL39029 survived to pH 4.5. Between pH 4.2 and pH 5.1, the latter three strains exhibited a peak in survival at pH 4.6-4.7 during log phase, suggesting that there may be a distinct acid tolerance system operating at this pH. SDS-PAGE of whole-cell, total membrane and outer-membrane fractions of the four strains prepared from pH 7.2 and pH 6.1 plate cultures revealed numerous differences in protein composition. Acidic conditions reduced the expression of the reduction modifiable outer-membrane protein Rmp, and induced the expression of many membrane proteins, including gonococcal hsp63. Immunoblotting studies with matched serum samples and strains from patients with pelvic inflammatory disease indicated that IgG recognition of outer-membrane components from strains cultured in acidic and neutral conditions was quite different. The results suggest that the immune system interacts with unique outer-membrane constituents on gonococci colonising sites at different pH. PMID- 9989643 TI - Antibiotic susceptibilities of Yersinia enterocolitica and Y. intermedia isolates from aquatic environments. AB - Of 37 Yersinia isolates from various aquatic environments, seven were Y. enterocolitica and 30 Y. intermedia. These isolates were biotyped, serotyped and tested for their susceptibility to 20 antibiotics. All Y. enterocolitica isolates were of biovar 1; those of Y. intermedia were distributed amongst four biovars (1, 2, 4 and 6). On the basis of combined biotyping and serotyping results, Y. enterocolitica isolates were distributed in five and Y. intermedia in 17 groups. With the exception of one Y. enterocolitica isolate which was resistant to tetracycline and streptomycin, the isolates were sensitive to the non-beta-lactam antibiotics. In contrast, various patterns of beta-lactam insensitivity were detected, including ampicillin and ticarcillin (35 isolates), cephalothin (33 isolates), carbenicillin (32 isolates), amoxycillin/clavulanate (23 isolates) and cefoxitin (22 isolates). No correlation between biotype or serotype and the susceptibility pattern of the isolates was apparent. Both inducible cephalosporinase activity against third-generation cephalosporins and inhibition of resistance to penicillins were detected in all Y. enterocolitica and Y. intermedia isolates by double-disk tests. PMID- 9989645 TI - Scanning electron microscopy characterisation of colonies of Candida albicans morphological mutants. AB - The ultrastructures of colonies of two stable UV-induced morphological mutants and their parental strain of Candida albicans grown on glucose-containing solid medium were investigated by scanning electron microscopy. The structures and ultrastructures of these three types of colonies were determined not only in terms of the proportions of blastospores, hyphae and pseudohyphae, but also with regard to the mode of budding of blastospores and the positions of these particular cell types within the colonies. Hyphae with an atypical appearance and branching characters were observed both in regular-wrinkled and in irregular wrinkled mutant colonies. Smooth colonies of the parental strain and the mutants exhibited the same hyphal network within the agar, suggesting that micro environmental factors in the agar overcame the effects of these mutations. PMID- 9989644 TI - Value of different methods for the characterisation of Aspergillus terreus strains. AB - To evaluate different methods for strain differentiation, 10 isolates of Aspergillus terreus from Germany and two epidemiologically unrelated strains were investigated. The sources of the isolates were patients with cystic fibrosis (4), immunosuppression (2), otitis externa (2), sinusitis (1) and endocarditis (1). Environmental isolates were obtained from a contaminated cell culture and from soil. The isolates did not differ in their macroscopic and microscopic morphology, in their protein patterns analysed by SDS-PAGE and in their susceptibility to amphotericin B and itraconazole. The RFLP analysis of total genomic DNA digested by EcoRI resulted in patterns that were too faint for interpretation. However, after hybridisation of the digested DNA with a short DNA probe of repetitive sequence, six different patterns were found. Based on the patterns of the randomly amplified polymorphic DNA (RAPD) with three primers, nine different genotypes were discriminate. RAPD patterns discriminated the epidemiologically unrelated reference strains (endocarditis isolate from Thailand, soil isolate from the USA) and the isolates from Germany. It is concluded that, in contrast to the phenotypic methods, the analysis of RAPD patterns is useful for strain differentiation of A. terreus. PMID- 9989646 TI - Saccharopolyspora rectivirgula from Quebec dairy barns: application of simplified criteria for the identification of an agent responsible for farmer's lung disease. AB - Saccharopolyspora rectivirgula (Micropolyspora faeni) is one of the major agents responsible for farmer's lung disease, a form of hypersensitivity pneumonitis. It is frequently isolated from the air of contaminated barns. The identification of this actinomycete is difficult because most of its phenotypic characteristics are variable and classical tests are not easy to perform on actinomycetes. Fatty acid analysis is very useful for the identification of these strains, but is not available except in some research or reference laboratories. Morphological (microscopic and macroscopic observations), physiological and biochemical tests (growth properties; macromolecules degraded; citrate utilisation and acid production from carbohydrates; resistance to antibiotics, lysozyme and heat), cell wall and fatty acid analyses and IgG analyses with serum from patients with farmer's lung were performed on 12 environmental isolates presumed to be S. rectivirgula and two control strains of S. rectivirgula. From this, a simple and rapid scheme for the identification of this actinomycete is proposed: optimal growth temperature (55 degrees C); colony appearance based on morphology (filamentous) and colour (beige to orange-brown); microscopic morphology (chains of spores on both aerial and substrate mycelium); growth on NaCl 10%; cell-wall analysis (type IV); and the verification of antibody response with serum from a patient with farmer's lung. This last criterion is important to confirm the immunogenicity of the strains identified as S. rectivirgula. This scheme provides an accurate and efficient way of identifying S. rectivirgula strains and evaluating exposure to this bacterium. The study shows the limited value and the lack of reproducibility of some classical biochemical tests. PMID- 9989647 TI - Combination of three typing methods for the molecular epidemiology of Aspergillus fumigatus infections. European Research Group on Biotype and Genotype of Aspergillus. AB - This study investigated the source of infection and strain relatedness of Aspergillus fumigatus isolates from bronchial colonisation and invasive aspergillosis (IA) in four transplant patients. Environmental isolates from the patient's home and from the hospital and infecting isolates were obtained for patient A who developed IA. Clinic environmental and colonising isolates were obtained for patient B. Sequential isolates were obtained from various organs from patient C who developed IA and also from patient D who had a bronchitic aspergillosis that developed into IA. Ninety-one A. fumigatus isolates were analysed by three typing methods: multi-locus enzyme electrophoresis (MLEE), random amplified polymorphic DNA (RAPD) and sequence-specific DNA primers (SSDP). The three combined typing methods demonstrated a greater differentiation of isolates than the typing methods used separately or in pairs. This demonstrated the genotypic variability of A. fumigatus and facilitated better epidemiological analysis. Large polymorphisms were demonstrated for each patient isolate between and colonies within various samples. The relatedness of the isolates suggested nosocomially acquired aspergillosis for patient B, but the source of infection for patient A remained unclear. The results suggested at least three multiple infections among the four patients. This study enabled the identification of the source of infection and strain relatedness, which in turn facilitates the development of preventive measures for patient management in the future. PMID- 9989648 TI - Differences in virulence of Sporothrix schenckii conidia related to culture conditions and cell-wall components. AB - A murine model was used to evaluate the virulence of Sporothrix schenckii conidia cultured for 4, 7, 10 or 12 days in Sabouraud's dextrose broth (SDB). A correlation was observed between length of culture and virulence. Mice infected intravenously with S. schenckii conidia cultured for 4 or 7 days showed 40-100% cumulative mortality. In contrast, mice infected with conidia from cultures grown for 10 or 12 days in SDB showed no mortality (100% survival). A much greater accumulation of fungal colony forming units (cfu) was observed in the lungs, livers and spleens of mice inoculated with conidia of S. schenckii cultured for 7 days than in mice infected with conidia cultured for 12 days. The livers of mice from the former group showed a widespread granulomatous reaction whereas mice inoculated with S. schenckii cultured for 12 days showed a more limited response with fewer granulomas. No difference in viability or replicative capacity was discerned for these S. schenckii cultured cells. However, the more virulent forms of the fungus showed differences in cell-wall sugar composition with rhamnose:mannose molar ratios of 1.7:1.0 for cells cultured for 4 days and 1.0:1.7 for conidia cultured for 12 days. These results suggest that the virulence of S. schenckii conidia may be determined by their cell-wall composition. PMID- 9989649 TI - Clonal structure of Providencia alcalifaciens strains isolated from diarrhoeal stools in Sao Paulo, Brazil. AB - Clonal analysis based on ribotyping demonstrated that Providencia alcalifaciens strains isolated mainly from diarrhoeal stools in Sao Paulo, Brazil, were clustered into two main groups. Eleven distinct ribotype patterns were identified with ClAI, EcoRV and MluI restriction endonucleases. P. alcalifaciens strains with invasive properties were of two ribotype patterns that differed from those identified among non-invasive strains. The ribotyping results confirmed that P. alcalifaciens strains associated with diarrhoeal disease in Sao Paulo represent distinct groups of strains. Although the invasive strains were isolated from different patients over an extended period they were clustered into two genetically related clones, which seemed to be distributed endemically in the population studied. PMID- 9989650 TI - Electron microscopy studies on Gardnerella vaginalis grown in conventional and biofilm systems. AB - The cell-wall characteristics of Gardnerella vaginalis grown in conventional and biofilm systems were studied by electron microscopy. The gram-positive nature of the cell wall was confirmed. Novel cell-wall particles which appeared to be associated with cell division were also identified, particularly in organisms of biofilm origin. PMID- 9989651 TI - Minimal inhibitory effect of male urine on detection of Chlamydia trachomatis by Roche Amplicor PCR. AB - A total of 1120 specimens of fresh urine from male patients was tested for Chlamydia trachomatis with the Roche Amplicor PCR Kit and an in-house PCR assay. The in-house PCR had an internal control to monitor inhibitory effects of clinical specimens on the PCR assay. All urine samples were processed within 24 48 h of collection and DNA was extracted on the same day that the assays were performed. Specimens that gave discrepant PCR results were tested by a reference laboratory with both the Roche Amplicor kit and their in-house PCR assay. Of the 1120 samples, 174 gave positive results in both assays and 942 gave negative results in both assays. Only one specimen showed an inhibitory effect on the in house PCR assays, as indicated by failure to produce the internal control PCR product. This specimen gave negative results by both assays. There were four discrepant results in the two PCR assays. One was a false negative result obtained with the Roche Amplicor kit and the remaining three discrepant results could not be resolved because there was an insufficient quantity of specimen. This study demonstrated that the Roche Amplicor kit could effectively detect C. trachomatis in urine specimens from this population of male patients with negligible inhibition of PCR. PMID- 9989652 TI - Assessment of benzydamine N-oxidation mediated by flavin-containing monooxygenase in different regions of rat brain and liver using microdialysis. AB - N-Oxidation of benzydamine (BZY) mediated by flavin-containing monooxygenase (FMO) was evaluated by microdialysis in vivo in different regions of rat brain and liver. The probe was implanted into local regions of the brain, such as the olfactory bulb, cerebral cortex, corpus striatum, hippocampus and cerebellum, or the hepatic lobe. By perfusing BZY via the probe, BZY N-oxide was identified in the dialysate. The estimated concentrations of BZY N-oxide in extracellular fluid were almost the same as those in the olfactory bulb, hippocampus and cerebral cortex, half the concentration in the hepatic lobe; however, the concentration in the corpus striatum was lower and that in the cerebellum was higher than in the other regions. These results demonstrate that the extracellular concentration of BZY N-oxide formed in vivo was unexpectedly high in every brain region. PMID- 9989653 TI - Structural characterization of recombinant human erythropoietins by fluorophore assisted carbohydrate electrophoresis. AB - Routine analysis of the carbohydrate moieties of a glycoprotein is critical for ensuring the consistent quality of biopharmaceutical products. Fluorophore assisted carbohydrate electrophoresis (FACE) is a recently introduced method for the separation, by polyacrylamide gel electrophoresis, of oligosaccharides labeled with 8-amino-naphthalene-1,3,6-trisulphonic acid (ANTS). In this study, we have evaluated the applicability of the FACE method to analysis of the carbohydrate moieties of three different recombinant human erythropoietins (rHuEPOs), two Chinese hamster ovary (CHO) cell-derived rHuEPOs, and one baby hamster kidney (BHK) cell-derived rHuEPO. The N-linked oligosaccharides released from the rHuEPOs were labeled with ANTS. Enzymic sequence analysis of the N linked oligosaccharides was performed by the FACE method. The results showed that the FACE method was useful for the analysis of sialo-, asialo-, and agalacto oligosaccharides in the same gel. Its usefulness for rapidly and reliably revealing the oligosaccharide profiles of given glycoproteins, and its reproducibility were also confirmed in this study. In conclusion, the method can be used for evaluating the quality consistency of recombinant glycoprotein products in terms of the carbohydrate moiety. PMID- 9989654 TI - Lectin-like protein fractions in lactic acid bacteria isolated from chickens. AB - Agglutination of fifty bacterial strains isolated from gastric-intestinal tract of chickens with yeasts treated with glutaraldehyde and glycine was assayed to study possible adhesion mechanisms to epithelia. It was found that Lactobacillus fermentum, Lactobacillus fermentum subsp. cellobiosus and Lactobacillus animalis agglutinated yeasts massively and this agglutination was inhibited in each strain by different representative sugars: agglutination was inhibited in three selected strains with 0.2 M mannose. The three strains agglutinated chicken red blood cells, but did not agglutinate human red blood cells, whereas the agglutinating capacity for other animal erythrocytes was variable. The lectins were partially purified on a Sephadex G-75 column and affinity chromatography. The molecular weight of each of the protein subunits was estimated as about 50-67 kDa using electrophoretic techniques. After treatment with lipase and metaperiodate modifications bacterial superficies and/or liberation of some structures produced an unspecific interaction with increase in the yeast agglutination and hemagglutination. The optimal conditions of work were: pH 6-7, Ca2+ 1 mM, Mg2+ 2 mM and 37-42 degrees C. PMID- 9989655 TI - Purification of a growth-suppressing factor for bovine artery endothelial cells from mouse lymphoma P388D1 cells. AB - A growth-suppressing factor for bovine artery endothelial cells (BAEGSF) was purified from the conditioned medium of a mouse lymphoma P388D1 cell culture in the presence of 100 microg/ml carboxymethylated curdlan. The purification steps included, in order, ammonium sulfate fractionation and eight stages of column chromatography on Macro-Prep Ceramic Hydroxyapatite, Q-Sepharose, Sephacryl S-300 HR, Matrex PBA-30, CHT II, Resource-Q, anti-bovine serum albumin (BSA) agarose, and Superdex 200HR columns. The purified BAEGSF showed two bands with silver staining on a sodium dodecyl sulfate polyacrylamide gel under reducing conditions (SDS-PAGE) and their molecular weights were estimated as approximately 55 and 63 kDa, while the molecular weight of the purified BAEGSF was estimated as about 65 kDa by gel filtration using Superdex 200HR. This result shows that BAEGSF obtained from Superdex 200HR chromatography is a partially purified preparation and suggests that one of the two bands on SDS-PAGE corresponds to BAEGSF. BAEGSF was shown not to have a lethal effect on endothelial cells, but had an inhibitory action on the proliferation of these cells. Furthermore, the growth-suppressing activity of BAEGSF for bovine artery endothelial cells (BAE) was not inhibited by anti-transforming growth factor-beta (TGF-beta), anti-tumor necrosis factor-alpha (TNF-alpha), and anti-interleukin-1 (IL-1) antibodies. These results suggest that BAEGSF is different from TGF-beta, TNF-alpha, and IL-1 which have been reported to inhibit BAE growth. PMID- 9989656 TI - S-(1,2-Dicarboxyethyl)glutathione in yeast: partial purification of its synthesizing enzyme. AB - S-(1,2-Dicarboxyethyl)glutathione (DCE-GS) was found in Saccharomyces cerevisiae, but not in bacterial species nor in a unicellular alga (Acetabularia acetabulum). The enzyme that catalyzes condensation of L-malate and glutathione (GSH) to form DCE-GS was partially purified from baker's yeast. It had a molecular mass of 49 kDa and was monomeric and the Km values were 2.2 and 1.4 mM for L-malate and GSH, respectively. The enzyme had a pH optimum of 7.5. DCE-GS levels in yeast cells were significantly higher in aerobic cultures than in anaerobic ones. DCE-GS was synthesized in cells cultured between 20 and 35 degrees C. PMID- 9989657 TI - Inhibitory mechanisms of glycoprotein fraction derived from Miscanthus sinensis for the immediate phase response of an IgE-mediated cutaneous reaction. AB - We investigated the inhibitory effect of the glycoprotein fraction (fraction 2) extracted from Miscanthus sinensi ANDERSSON (M. sinensis) on biphasic cutaneous reactions in mice passively sensitized with IgE. Biphasic skin reactions with peak responses at 1 (IPR, immediate phase reaction) and 24 h (LPR, late phase reaction) were caused by passive sensitization with an anti-dinitrophenol IgE monoclonal antibody (anti-DNP IgE mAb) followed by an epicutaneous challenge of 0.1% dinitrofluorobenzene (DNFB) in 100% ethanol. Intraperitoneal injection of fraction 2 before the DNFB challenge significantly inhibited the biphasic ear swelling response in passively sensitized mice in a dose-dependent manner (1-30 mg/kg). We also found that fraction 2 was effective at inhibiting the vascular permeability in mouse ear induced by an injection of compound 48/80, histamine or serotonin. In addition, fraction 2 inhibited scratching behavior as well as ear edema observed within 2 h after DNFB challenge. Marked inhibition was observed in both passively sensitized and non-sensitized mice. The locomotor activity of mice was also reduced by the administration of fraction 2 as well as by diphenhydramine. These results suggest that the inhibitory effect of glycoprotein fraction 2 of M. sinensis on an IgE-mediated allergic inflammatory reaction is due to the protection of mediator-induced vascular permeability and that in addition to the inhibition of an inflammatory reaction, a sedative action is responsible for the inhibition of allergy-induced scratching responses. PMID- 9989658 TI - Electrophysiological effects of newly synthesized 1,4-pyridothiazepines on various guinea pig heart muscle preparations. AB - Slow channel blockers play a major role in the treatment of cardiovascular disease. The intention of this study was to investigate the electrophysiological properties of MM 4 (1-[N-[2-(3,4-dimethoxy-phenyl)ethyl]-N-methylaminoacetyl] 1,2,3,4 -tetrahydropyrido[2,3-b][1,4]thiazepine fumarate) and MM 6 (1-[N-[2-(3,4 dimethoxy-phenyl)ethyl]-N-methylaminopropionyl]-1,2, 3,4-tetrahydropyrido[2,3 b][1,4]thiazepine fumarate), two newly synthesized compounds structurally related to KT-362 (5-[3-[[2-(3,4-dimethoxy-phenyl)ethyl]-amino]-1-oxopropyl]-2,3,4,5 tetra -hydro-1,5-benzothiazepine fumarate), by means of the conventional intracellular microelectrode technique. In various guinea pig heart muscle preparations, MM 4 and MM 6 exerted very similar effects though the action of MM 6 was more pronounced. In a concentration range from 3 to 100 micromol/l the compounds did not produce any significant change in transmembrane action potential parameters of papillary muscle and left atria, whereas the action potential duration at 20% and 50% time to repolarization in spontaneously beating Purkinje fibers was significantly shortened. In sinoatrial nodes action potential amplitude, Vmax, rate of activity and slope of slow diastolic depolarization were decreased, whereas the time to 50% and 90% repolarization was significantly prolonged. A decrease in the slow calcium inward current may account for the observed effects. In contrast to KT-362, MM 4 and MM 6 do not seem to affect the fast sodium inward current. It was concluded that replacement of the 1,5 benzothiazepine nucleus by a 1,4-pyridothiazepine structure and/or methylation of the side chain may weaken or even eliminate sodium channel blocking ability while calcium antagonistic characteristics are preserved. Shortening of the side chain might result in a general loss of activity. PMID- 9989659 TI - Acceleration of development of diabetic cataract by hyperlipidemia and low high density lipoprotein in rats. AB - Diabetic cataracts are thought to be caused by hyperglycemia associated with disturbed glucose metabolism. Diabetes mellitus often involves abnormal lipid metabolism in addition to abnormal glucose metabolism. To date, however, very few studies have counted hyperlipidemia as a risk factor for diabetic cataracts. The present study was undertaken to determine whether this abnormal lipid metabolism is a risk factor for diabetic cataracts in rats. Cataracts were caused by streptozotocin (STZ) administration in the ordinary diet or cholesterol rich diet fed rats. When rats with STZ (65 mg/kg)-induced diabetes mellitus were fed an ordinary diet, cataracts became evident at 9 weeks in 26.7% of animals, and increased to an incidence of 53.3% after 10 weeks of STZ treatment. However, in rats with STZ-induced diabetes mellitus that were fed a cholesterol rich diet to induce severe hyperlipidemia and low high density lipoprotein (HDL) cholesterol, cataracts were observed one week earlier, after 8 weeks of treatment, in 40.0% of animals, with an increase to a 53.3% incidence and an 86.7% incidence after 9 and 10 weeks of STZ treatment, respectively. Plasma glucose levels did not differ between the groups. These results suggest that hyperlipidemia and low HDL cholesterol are associated with an earlier onset and an elevated incidence of diabetic cataracts. We then investigated the relationship between plasma lipids and cataracts by STZ (45-85 mg/kg) administration. The results showed that the onset of cataracts correlated positively with plasma total cholesterol, triglyceride, non-HDL cholesterol and glucose levels, and negatively with HDL cholesterol levels. The results of this study suggest that hyperlipidemia and low HDL cholesterol levels may be risk factors for the onset of diabetic cataracts and that diabetic cataracts may be accelerated by hyperlipidemia and low HDL cholesterol in rats. PMID- 9989660 TI - Preparation and characteristics of antibacterial sepiolite containing povidone iodine as a useful pharmaceutical product for patient care. AB - Povidone-iodine (PVP-I), an antibacterial medicine, was infiltrated in sepiolite (SPL). The available iodine content in this new pharmaceutical product, a sepiolite preparation containing povidone-iodine (PVP-I-SPL), was retained at 98.9 and 98.3% during storage at 40 degrees C for 3 and 6 months, respectively. The effective removal of various gasses, including ammonia, hydrogen sulfide, ethylmercaptan and acetaldehyde, was achieved by use of PVP-I-SPL. Especially, the concentration of ammonia gas was reduced more than half after 30 min of exposure, suggesting that PVP-I-SPL has excellent ability to adsorb ammonia gas. The satisfactory antibacterial effect of PVP-I-SPL was also obtained by testing its minimum bactericidal concentration (MBC). No irritation reactions to the rabbit auricle or ophthalmic mucosa or to human skin were observed by the skin irritation test. The PVP-I-SPL preparation has bactericidal activity and gas adsorbing ability; therefore, this pharmaceutical product should be useful for the prevention of infections and deodorization in hospital rooms and houses, as well as in nursing homes for elderly people. PMID- 9989661 TI - Comparison of immunopharmacological actions of 8 kinds of kampo-hozais clinically used in atopic dermatitis on delayed-type hypersensitivity in mice. AB - We studied here the effects of 8 kinds of kampo-hozais clinically used to treat atopic dermatitis (Shofu-san, Toki-inshi, Unsei-in, Oren-gedoku-to, Ji-zuso-ippo, Jumi-haidoku-to, Juzen-taiho-to, Hochu-ekki-to) on delayed-type hypersensitivity (DTH), using three types of murine models such as picryl chloride (PC)-induced (contact hypersensitivity), sheep red blood cell (SRBC)-induced (Jones-Mote's reaction) and tuberculin-induced DTH response, in order to clarify and to compare the immunopharmacological action of kampo-hozais. Most of the kampo-hozais investigated here suppressed PC-induced contact hypersensitivity, especially at the inductive phase. Comparing the efficacies of these kampo-hozais on the three types of DTH responses in mice, they were generally divided into 4 groups. Shofu san significantly reduced PC-induced and tuberculin-induced DTH responses but not a SRBC-induced DTH response. On the other hand, Toki-inshi reduced contact hypersensitivity, tuberculin type DTH response and Jones-Mote's reaction. Ji-zuso ippo and Juzen-taiho-to suppressed mainly Jones-Mote's reaction, and Unsei-in, Oren-gedoku-to and Jumi-haidoku-to intensively suppressed contact hypersensitivity. We thought that these findings could help us understand how to use these kampo-hozais properly. PMID- 9989662 TI - Sustained release liquid preparation using sodium alginate for eradication of Helicobacter pyroli. AB - We prepared a new liquid preparation for eradication of Helicobacter pylori (HP), and examined drug release in vitro and in vivo. The liquid preparation mainly consisted of a sodium alginate (AG) aqueous solution containing ampicillin (ABPC), an antibiotic drug, or methylene blue, a dye. Drug release was retarded by Ca pre-treatment (0.10 M, 20 s) of the AG preparation in in vitro drug release studies due to gel-formation at the liquid surface. In in vivo experiments, the AG preparations were administered orally to rats. The rats were divided into two groups, with or without pre-administration of ranitidine hydrochloride (RH, an H2 blocker). The total remaining % of ABPC in the stomach was high in the rats administered the AG preparation compared to the ABPC solution. The AG preparation might float in the stomach without adhering to the gastric wall in the rats without pre-administration of RH. The total remaining % of ABPC at 30 min was almost 100% in the RH pre-administration rats administered the AG preparation, and about 80% of the drug existed in fraction 2 (implying adhesion of the preparation on the gastric mucus). At 60 min, the total remaining % in the AG preparation plus Ca (mean 87%) increased about 2-fold compared to that in the AG preparation alone (mean 44%). In this case, a large portion of the remaining ABPC also existed in fraction 2. This preparation may be useful for eradication of HP. PMID- 9989663 TI - Evaluation of induction of CYP3A mRNA using the HepG2 cell line and reverse transcription-PCR. AB - Cytochrome P-450 3A (CYP3A) is a drug-metabolizing enzyme dominant in the human liver. We have designed a useful method for evaluation of induction of CYP3A mRNA by various drugs using HepG2 cells known to retain liver-cellular functions. Using semi-quantitative reverse transcription-PCR (RT-PCR), we demonstrated that cultured HepG2 cells constitutively expressed CYP3A mRNA. This mRNA was expressed at high levels in culture for several days and was further induced by several drugs (e.g. rifampicin (RFP), dexamethasone). Treatment of HepG2 cells with RFP induced CYP3A mRNA in a dose- and time-dependent manner. Cells in culture for 48 h with 1 and 50 micromol/l RFP increased 2.7- and 5.0-fold in CYP3A mRNA expression in comparison with untreated controls, respectively. In contrast, no change in the amount of CYP3A mRNA was observed when the cells were treated with cimetidine which has been shown to inhibit CYP3A activity. Our method using a combination of HepG2 cells and RT-PCR allowed evaluation of the degree of induction of CYP3A mRNA both easily and rapidly. PMID- 9989664 TI - Enhanced absorption of cyclosporin A by complexation with dimethyl-beta cyclodextrin in bile duct-cannulated and -noncannulated rats. AB - The enhancing effects of dimethyl-beta-cyclodextrin (DM-beta-CyD) on the absorption of cyclosporin A (CsA) after oral administration to rats under bile duct-cannulated and -noncannulated conditions were investigated. The dissolution rate of CsA was markedly augmented by complexation with DM-beta-CyD. In a closed loop in situ study, DM-beta-CyD considerably increased the cumulative amounts of CsA in the mesenteric venous blood after injection of the aqueous CsA suspension into the small intestinal sac of rats. In addition, the cumulative amount ratio of M1, the dominant metabolite of CsA in rats, to CsA in the mesenteric venous blood for up to 40 min after the injection of the CsA-DM-beta-CyD suspension into the sac was lower than that of the CsA suspension alone. DM-beta-CyD inhibited the bioconversion of CsA in the small intestinal microsomes of rats. These results indicate that the bioconversion of CsA was abated by complexation with DM beta-CyD. An in vivo study revealed that DM-beta-CyD increased the transfer of CsA to blood, not lymph, with low variability in the absorption after oral administration of the CsA suspension to rats. The variability of bioavailability of DM-beta-CyD complex was lower than that of Sandimmune, although the extent of bioavailability of DM-beta-CyD was only a little higher than that of Sandimmune. The bioavailability of CsA or its DM-beta-CyD complex was appreciably decreased by the cannulation of the bile duct of rats, and the extent of the lowering in the bioavailability in the presence of DM-beta-CyD was much less serious than that of CsA alone. The present results suggest that DM-beta-CyD is particularly useful in designing oral preparations of CsA with an enhanced bioavailability and a reduced variability in absorption. PMID- 9989666 TI - A rapid and simple detection of genetic defects responsible for the phenotypic polymorphism of cytochrome P450 2C19. AB - A rapid and simple cytochrome P450 (CYP) 2C19 genotyping system was established by making several modifications in previously reported procedures. PCR conditions were modified to be capable of simultaneous amplification of CYP2C19m1 and CYP2C19m2 regions. Intensive bands of 169 bp for the CYP2C19m1 region and 329 bp for the CYP2C19m2 region with low background were obtained by using PCR condition involving an initial denaturation of 5 min at 94 degrees C, 35 cycles of 1 min at 94 degrees C; 1 min at 53 degrees C; 1 min at 72 degrees C, and final extension of 5 min at 72 degrees C. Next, the optimal restriction enzyme digestion conditions were determined by using PCR products from a subject of wt/wt genotype. Both products were completely digested with 5 U of the corresponding enzyme (Sma I for CYP2C19m1 and Bam HI for CYP2C19m2) for 1 h incubation at an optimal temperature. The incidence (16%; 5/32) of subjects homozygous for mutant alleles determined by an established assay system agreed well with the incidence of the poor metabolizer (PM) phenotype in the Japanese population. The established genotyping system would, therefore, be applicable to the clinical laboratory testing of patients with a PM phenotype of CYP2C19 to select appropriate and effective medication. PMID- 9989665 TI - Biological activities of 1,1,6-trisubstituted indanes: beyond magainin 2. AB - MSI-78 is a peptide analog of naturally occurring magainin 2 isolated from the skin of Xenopus laevis. The peptide is known to have one of the strongest antibacterial activities in magainin 2 analogs against methicillin-resistant Staphylococcus aureus (MRSA). To find novel compounds superior to MSI-78, we have further designed, synthesizing 1,1-di(4-aminobutyl)-6-benzylindane (PM4) and 1,1 dibenzyl-6-(4-aminobutyl) indane (PM5), and tested their inhibitory ability of the growth of S. aureus. In an in vitro assay, PM4 showed the same antibacterial activity against the bacterium as MSI-78, and non-hemolytic activity against human red blood cells (RBCs) at the MIC (minimum inhibitory concentration) value, in contrast to the latter. On the other hand, PM5 showed stronger antibacterial activity than MSI-78, but being still accompanied with hemolysis at the MIC value. Otherwise, stronger decarboxylase activity for oxaloacetate was observed in PM5, rather than magainin 2 analogs or Oxaldie 1 as a control peptide, but not in PM4. PMID- 9989667 TI - Purification and characterization of glycyrrhetic acid mono-glucuronide beta-D glucuronidase in Eubacterium sp. GLH. AB - Glycyrrhetic acid mono-glucuronide (GAMG), 1-(18beta-glycyrrhet-3-yl)-beta-D glucopyranuroic acid, was hydrolyzed to glycyrrhetic acid (GA) by GAMG beta-D glucuronidase in Eubacterium sp. GLH from human intestinal bacteria. The enzyme had an optimum pH of 5.0 and was purified from a crude extract by Butyl Toyopearl 650 S, Toyopearl HW-55 S, Hydroxyapatite and DEAE-Toyopearl 650 M column chromatography. The purified enzyme showed a specific activity of 495 nmol/min/mg protein and a single band on Coomassie brilliant blue staining and a molecular weight of about 43 kDa on sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis. The apparent molecular weight was 49.5 kDa, as estimated by Toyopearl HW-55 S column chromatography. Also, the enzyme seemed to have a sulfhydryl group(s) in its active site with a Km value of 77 x 10(-3) M. PMID- 9989668 TI - Isolation of deoxycytidine kinase from Ehrlich carcinoma cells by affinity chromatography based on a substrate analog, 2'-C-cyano-2'-deoxy-1-beta-D arabinofuranosyl-N4-palmitoylcytosine++ +. AB - Deoxycytidine kinase from Ehrlich carcinoma cells was purified 10400-fold by ammonium sulfate fractionation and affinity chromatography using Sepharose 4B coupled to 2'-C-cyano-2'-deoxy-1-beta-D-arabinofuranosyl-N4-palmitoylcytosine , with a yield of 45%. The purified enzyme preparation showed a single major band with a molecular weight of 32000 on SDS-PAGE. The enzyme phosphorylated deoxyadenosine, deoxyguanosine, cytidine, and several deoxycytidine analogues as well as deoxycytidine. Also, the kinetic parameters of the enzyme for the substrates were estimated. PMID- 9989669 TI - Effects of Keishi-ka-shakuyaku-to (Gui-Zhi-Jia-Shao-Yao-Tang) on diarrhea and small intestinal movement. AB - The present study was conducted to determine the characteristics of the effects of Keishi-ka-shakuyaku-to (Gui-Zhi-Jia-Shao-Yao-Tang; TJ-60) on diarrhea. Significant repression was noted by TJ-60 at 1000 mg/kg, p.o. for diarrhea induced by pilocarpine, barium chloride or castor oil. Under normal conditions, TJ-60 did not influence small intestinal transit by its oral treatment even at 1000 mg/kg, however, it dose-dependently improved the acceleration of such transit caused by neostigmine. TJ-60 did not influence the resting tonus in isolated small intestine, but did selectively inhibit low frequency electrostimulated contractions. These results indicate that the antidiarrheal effects of TJ-60 may be due to the inhibition of excessively accelerated small intestinal movement, and that the inhibition of acetylcholine release by parasympathetic nerves is partly involved in the mechanism of this antidiarrheal action. PMID- 9989670 TI - Synergistic effect of naphthoquinones on the mutagenicity of nitroarene. AB - Nitro reduction is a critical step in the mutagenic activation of nitroarene. Nitroarene and quinone are known to be reduced by common enzymes, and thus, naphthoquinone (NQ) was studied for its effects on the mutagenicity of nitroarene in the Ames test using Salmonella typhimurium TA98 without S9. The mutagenicity of 1,3-dinitropyrene in TA98 was found to increase 9- and 6-fold as much in the presence of 70 nmol/plate of 2-methyl-1,4-NQ and 2-hydroxy-1,4-NQ, respectively. Mutagenicity also became greater in 1,3,5-trinitronaphthalene, 1-nitropyrene and 3-nitrofluoranthene. Seventy nmol/plate of 2-methyl-1,4-NQ increased the mutagenicity of 1-nitropyrene by 10.5-fold as much. PMID- 9989671 TI - Effect of dimethyl-4,4'-dimethoxy-5,6,5',6'-dimethylenedioxybiphenyl-2,2'- dicarboxylate (DDB) on chemical-induced liver injury. AB - The effects of orally administered dimethyl-4,4'-dimethoxy-5,6,5',6'-dimethylene dioxybiphenyl-2,2'-d icarboxylate (DDB) on the hepatotoxicity induced by carbon tetrachloride, acetaminophen or ethanol were investigated in rats and mice. Either single or repeated DDB pretreatment (50 or 200 mg/kg) did not alter the hepatotoxicity induced by carbon tetrachloride (0.2 or 1.0 ml/kg, i.p.) in female rats as indicated by increases in the activity of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and sorbitol dehydrogenase (SDH) in serum. The hepatotoxicity of acetaminophen (350 mg/kg, i.p.) was also unaffected in male mice pretreated with DDB (50 mg/kg/d) for a week. However, DDB administration (50 mg/kg/d for 7 d) decreased the hepatic fatty degeneration induced by repeated ethanol treatment (0.75 g/kg, i.p., x2 times a day for a week) in rats as shown by the accumulation of triglycerides and cholesterol in the liver. Malondialdehyde (MDA) formation in liver homogenates was inhibited by DDB treatment. The significance of the action of DDB on alcoholic fatty liver generation in clinical settings is discussed. PMID- 9989672 TI - Protein chemotaxonomy of the solanaceae. VI. Amino acid sequence of ferredoxin from Nicotian tabacum. AB - The complete amino acid sequence of [2Fe-2S] ferredoxin from Nicotiana tabacum has been determined by automated Edman degradation of the entire Cm-protein and of the peptides obtained by trypsin and Asp-N endoproteinase digestions. This ferredoxin exhibited 9, 10, 8, and 10 differences respectively in its amino acid sequence, when compared with the ferredoxins of Datura stramonium, D. metel, D. arborea, and Physalis alkekengi var.francheti but 17-28 differences for other angiosperms, and 34-37 differences for fern and horsetails. These results are in agreement with the taxonomic position for these plants. PMID- 9989673 TI - Cytotoxicity and pharmacokinetics of 1-beta-D-arabinofuranosyl-2-thiocytosine, a 2-sulphur substituted derivative of cytarabine. AB - 1-(beta-D-Arabinofuranosyl)-2-thiocytosine (araSC), a 2-substituted derivative of cytarabine (araC), has been investigated for its cytotoxicity, enzymatic stability, plasma concentration-time profile in mice, and cytokinetics. This derivative showed strong cytotoxicity in several mammalian cell lines, although activity (IC50s) was weaker than araC. Greater stability to mouse cytidine deaminase was observed; the half-life in the presence of the enzyme was about 4 times longer than that of araC. The plasma concentration-time profile in mice in vivo showed prolonged retention of araSC when compared with araC. Cytokinetic study using flow cytometry indicated a non-S-phase specific effect of this compound. PMID- 9989674 TI - Modification of ceftibuten transport by changes in lipid fluidity caused by fatty acid glycerol esters. AB - The effects of various fatty acid glycerol esters (FAGE) on the transport of ceftibuten in rat intestinal brush-border membrane vesicles (BBMV) were investigated. The HLB numbers of FAGE used were in the range of 6.5 to 15.7. The ceftibuten uptake by BBMV was examined by a rapid filtration method in the presence or absence of FAGE of a non-solubilizing concentration (0.03%, w/v). Tetraglycerol monostearate, hexaglycerol monostearate, hexaglycerol sesquistearate, hexaglycerol tristearate and decaglycerol tristearate were found significantly to enhance the ceftibuten uptake under an inward H+-gradient condition, while FAGE with oleate or laurate did not affect it. The extent of ceftibuten uptake with FAGE correlated with the HLB of the esters (r= -0.90, p<0.001). To elucidate the mechanism of its enhancing action, the effects of FAGE on the membrane lipid fluidity were examined using the fluorescence probes diphenylhexatriene (DPH) and trimethylammonium diphenylhexatriene (TMA-DPH) which distribute in the hydrophobic inner and outer regions of the lipid layer, respectively. The increase in ceftibuten uptake induced by FAGE proved to correlate with an increase in fluidity of the outer lipid layer (r= -0.83, p<0.003) but not the inner lipid layer of BBMV. Hence, the enhancing effect of FAGE with the lower HLB on the ceftibuten transport in the presence of the H+ gradient should, at least in part, be explained by the interaction with the outer lipid regions of BBMV. PMID- 9989675 TI - An antimutagenic metabolite, streptovaricin C, isolated from Streptomyces sp. AB - Streptomyces sp. KM1-30 was isolated from soil as a producer of antimutagens by screening with a modified Ames test. The chemical structure of the antimutagenic metabolite was identified as streptovaricin C, which is known to inhibit DNA dependent RNA polymerase from E. coli and RNA dependent DNA polymerase from RNA tumor viruses, by MS and 1H-, 13C-NMR analyses. Addition of streptovaricin C to the cultures of UV treated Salmonella typhimurium TA100 or Trp-P-2-treated S. typhimurium TA98 decreased the frequency of mutation without a decrease in viable cell counts. The effect of streptovaricin C to the mutation induced by UV and Trp P-2 was not desmutagenic, but antimutagenic. PMID- 9989676 TI - Alcohol intake and body weight: a paradox. PMID- 9989677 TI - Dietary supplement or drug? The case of cholestin. PMID- 9989678 TI - Vitamin A assessment by the isotope-dilution technique: good news from Guatemala. PMID- 9989679 TI - Potential mechanisms of metabolic imprinting that lead to chronic disease. AB - This review synthesizes a subset of human epidemiologic and experimental animal studies that suggest that early nutrition affects susceptibility to chronic diseases in adulthood. These studies provide evidence that biological mechanisms may exist to "memorize" the metabolic effects of early nutritional environments. However, hypothesis-driven investigations of potential mechanisms have been scant. Thus, our understanding of the biology underlying metabolic imprinting is incomplete. A working definition of metabolic imprinting is proposed, emphasizing the adaptive nature and limited ontogenic window of the mechanisms putatively responsible for these relations. Five specific candidate mechanisms of metabolic imprinting are elaborated: 1) induced variations in organ structure, 2) alterations in cell number, 3) clonal selection, 4) metabolic differentiation, and 5) hepatocyte polyploidization. Last, experimental approaches for probing potential mechanisms with animal models are discussed. PMID- 9989680 TI - Metabolic and weight-loss effects of a long-term dietary intervention in obese patients. AB - BACKGROUND: Obesity is a chronic disease that has become one of the most serious health problems in Western society. OBJECTIVE: We assessed the long-term effects of an energy-restricted diet combined with 1 or 2 daily meal replacements on body weight and biomarkers of disease risk in 100 obese patients. DESIGN: Phase 1 consisted of a 3-mo, prospective, randomized, parallel intervention study of 2 dietary interventions to reduce weight. The energy-restricted diet (5.2-6.3 MJ/d) consisted of conventional foods (group A) or an isoenergetic diet with 2 meals and 2 snacks replaced daily by energy-controlled, vitamin-and-mineral supplemented prepared foods (group B). Phase 2 consisted of a 24-mo, case control, weight-maintenance study with an energy-restricted diet and 1 meal and 1 snack replaced daily for all patients. RESULTS: Total weight loss (as a percentage of initial body weight) was 5.9+/-5.0% in group A and 11.3+/-6.8% in group B (P < 0.0001). During phase 1, mean weight loss in group B (n = 50) was 7.1+/-3.5 kg, with significant reductions in plasma triacylglycerol, glucose, and insulin concentrations (P < 0.0001). Group A patients (n = 50) lost an average of 1.3+/-2.2 kg with no significant improvements in these biomarkers. During phase 2, both groups lost on average an additional 0.07% of their initial body weight every month (P < 0.01). During the 27-mo study, both groups experienced significant reductions in systolic blood pressure and plasma concentrations of triacylglycerol, glucose, and insulin (P < 0.01). CONCLUSION: These findings support the hypothesis that defined meal replacements can be used for successful, long-term weight control and improvements in certain biomarkers of disease risk. PMID- 9989681 TI - The appetizing effect of an aperitif in overweight and normal-weight humans. AB - BACKGROUND: Epidemiologic studies have shown alcohol consumption to be inversely as well as positively related to body weight and body fat. Metabolic studies have shown an increase in energy intake as well as compensation after alcohol consumption. OBJECTIVE: Our objective was to assess the effects on energy intake of an aperitif compared with those of a water appetizer and 3 fruit juice appetizers. DESIGN: Fifty-two men and women aged 20-45 y with a body mass index (in kg/m2) between 20 and 32 were randomly given 1 MJ (340 mL) alcohol (wine or beer), fat (cream fruit juice), protein (protein fruit juice), carbohydrate (grape juice), or water, or no preload 30 min before an ad libitum lunch consumed from the universal eating monitor. RESULTS: Energy intake (3.5+/-0.3 MJ compared with 2.7+/-0.2 MJ, P < 0.001) and eating rate were higher (44+/-3 g/min compared with 38+/-3 g/min, P < 0.01), meal duration was longer (14 min compared with 12.0 min, P < 0.01), satiation started to increase later (3.5 min compared with 1.5 min, P < 0.01), and eating was prolonged after maximum satiation (2.5 min compared with 0.6 min, P < 0.01) after an aperitif than after a fat, protein, or carbohydrate appetizer,. Twenty-four-hour energy intake was higher on a day that an aperitif was consumed than after water or no preload. CONCLUSION: Twenty-four hour energy intake was elevated with a 1-MJ aperitif but not with a 1-MJ liquid carbohydrate, fat, or protein appetizer. PMID- 9989682 TI - A vitamin E concentrate rich in tocotrienols had no effect on serum lipids, lipoproteins, or platelet function in men with mildly elevated serum lipid concentrations. AB - BACKGROUND: Tocotrienols, lipid-soluble antioxidants with vitamin E activity, have been reported to lower LDL-cholesterol concentrations and platelet aggregation in men, but results are contradictory. OBJECTIVE: To examine in detail the effects of a vitamin E concentrate rich in tocotrienols on serum lipoproteins and on platelet function in men at risk for cardiovascular disease. DESIGN: In this randomized, double-blind, placebo-controlled parallel trial, 20 men received daily for 6 wk 4 capsules, each containing 35 mg tocotrienols and 20 mg alpha-tocopherol; 20 other men received 4 capsules daily, each providing 20 mg alpha-tocopherol. All men had concentrations of serum total cholesterol between 6.5 and 8.0 mmol/L or lipoprotein(a) concentrations > 150 mg/L. RESULTS: Compliance was confirmed by changes in serum tocopherol and tocotrienol concentrations. Serum LDL cholesterol in the tocotrienol group was 4.80 mmol/L before and 4.79 mmol/L after intervention, and increased from 4.70 to 4.86 mmol/L in the placebo group (95% CI for the difference: -0.54, 0.19 mmol/L; P = 0.333). Also, changes in HDL cholesterol, triacylglycerol, lipoprotein(a), and lipid peroxide concentrations did not differ between the groups. After adjustment for differences in initial values, no effects were found on collagen-induced platelet aggregation velocity, maximum aggregation, or thromboxane B2 formation in citrated whole blood. ATP release, however, was lower in the tocotrienol group. Urinary thromboxane B2 and 11-keto-thromboxane B2 concentrations and coagulation and fibrinolytic measures did not change. CONCLUSION: The tocotrienol supplements used had no marked favorable effects on the serum lipoprotein profile or on platelet function in men with slightly elevated lipid concentrations. PMID- 9989683 TI - Dietary oleic and palmitic acids and postprandial factor VII in middle-aged men heterozygous and homozygous for factor VII R353Q polymorphism. AB - BACKGROUND: The R353Q genotype is a major determinant of factor VII coagulant (FVIIc) activity, which is associated with an increased risk of ischemic heart disease (IHD) and elevated plasma triacylglycerol concentrations. OBJECTIVE: The objectives were to 1) compare the effects of meals rich in palmitate or oleate with those of a meal low in fat on FVIIc in subjects with moderately elevated plasma nonfasting triacylglycerol concentrations and 2) determine whether the postprandial increase in FVIIc induced by dietary oleate differs in carriers of the Q allele. DESIGN: Fifty-two men aged >52 y with nonfasting plasma triacylglycerol concentrations between 2 and 5.5 mmol/L were randomly assigned to receive isoenergetic (5.1 MJ) meals providing 50 g high-oleate or high-palmitate oils or a low-fat meal providing 15 g high-oleate oil. In a second study, 17 men aged >52 y who were heterozygous for factor VII R353Q polymorphism were age matched with subjects homozygous for the R allele and their responses to a 50-g, high-oleate meal were measured. RESULTS: FVIIc decreased by 11% after the low-fat meal. FVIIc increased by 9% and FVIIa (the activated form of FVII) increased by 55% after the high-oleate meal, whereas FVIIc did not change but FVIIa increased by 25% after the high-palmitate meal. Fasting FVIIc and FVIIa concentrations were 24% and 48% lower, respectively, in men with the RQ genotype than in men with the RR genotype but increased postprandially in both groups with no evidence of a genotype interaction. CONCLUSIONS: A high-fat meal rich in oleate increases FVIIa, whereas a low-fat meal does not, in men at high risk of IHD, independent of R353Q genotype. PMID- 9989684 TI - A novel source of wheat fiber and protein: effects on fecal bulk and serum lipids. AB - BACKGROUND: Wheat fiber is a laxative and wheat protein may affect blood lipids. OBJECTIVE: We therefore tested the effects on laxation and serum lipid metabolism of a novel source of wheat fiber and protein produced by the amylolytic digestion of starch from wheat. DESIGN: Twenty-four healthy men and women consumed 3 different test cereals in random order, each for 2 wk. The test supplement and the positive control, American Association of Cereal Chemists wheat bran supplement, both provided the same amount of fiber (21 g/d) and the negative control supplement provided 1.7 g fiber/d. RESULTS: The test supplement and the positive control supplement increased fecal bulk similarly (239.5+/-19 and 216.7+/-19 g/d, respectively) and significantly more than did the negative control supplement (165.6+/-16 g/d, P < 0.010). Compared with the negative and positive control supplements, the week 2 value of the test supplement for the ratio of total to HDL cholesterol was significantly reduced (P = 0.046). CONCLUSION: We conclude that the product of amylolytic digestion of starch from wheat flakes, which is high in wheat fiber and protein, has a fecal bulking effect similar to that of wheat bran and may have a beneficial effect on serum lipids. PMID- 9989685 TI - Cholesterol-lowering effects of a proprietary Chinese red-yeast-rice dietary supplement. AB - BACKGROUND: We examined the cholesterol-lowering effects of a proprietary Chinese red-yeast-rice supplement in an American population consuming a diet similar to the American Heart Association Step I diet using a double-blind, placebo controlled, prospectively randomized 12-wk controlled trial at a university research center. OBJECTIVE: We evaluated the lipid-lowering effects of this red yeast-rice dietary supplement in US adults separate from effects of diet alone. DESIGN: Eighty-three healthy subjects (46 men and 37 women aged 34-78 y) with hyperlipidemia [total cholesterol, 5.28-8.74 mmol/L (204-338 mg/dL); LDL cholesterol, 3.31-7.16 mmol/L (128-277 mg/dL); triacylglycerol, 0.62-2.78 mmol/L (55-246 mg/dL); and HDL cholesterol 0.78-2.46 mmol/L (30-95 mg/dL)] who were not being treated with lipid-lowering drugs participated. Subjects were treated with red yeast rice (2.4 g/d) or placebo and instructed to consume a diet providing 30% of energy from fat, <10% from saturated fat, and <300 mg cholesterol daily. Main outcome measures were total cholesterol, total triacylglycerol, and HDL and LDL cholesterol measured at weeks 8, 9, 11, and 12. RESULTS: Total cholesterol concentrations decreased significantly between baseline and 8 wk in the red-yeast rice-treated group compared with the placebo-treated group [(x+/-SD) 6.57+/-0.93 mmol/L (254+/-36 mg/dL) to 5.38+/-0.80 mmol/L (208+/-31 mg/dL); P < 0.001]. LDL cholesterol and total triacylglycerol were also reduced with the supplement. HDL cholesterol did not change significantly. CONCLUSIONS: Red yeast rice significantly reduces total cholesterol, LDL cholesterol, and total triacylglycerol concentrations compared with placebo and provides a new, novel, food-based approach to lowering cholesterol in the general population. PMID- 9989686 TI - Anthropometric status and cataract: the Salisbury Eye Evaluation project. AB - BACKGROUND: Weight or body mass index (BMI; in kg/m2) is frequently identified as a risk factor for cataract, but the nature of the association is unclear. OBJECTIVE: We aimed to characterize the relation between BMI and stature and risk of different types of cataract. DESIGN: We analyzed data from participants in the Salisbury Eye Evaluation (SEE), a cross-sectional survey of visual status and demographic, nutritional, and environmental factors conducted between 1993 and 1995 in a representative sample of community-dwelling older persons in Salisbury, MD. Multiple logistic regression techniques were used to compare risk factors between individuals with nuclear, cortical, or posterior subcapsular (PSC) opacities and individuals with no cataract. RESULTS: Risk of nuclear opacification was greater in participants with lower BMIs [adjusted odds ratio of 1.13 (95% CI: 1.02, 1.27) with a BMI of 22.5 compared with 28.0] and of taller stature [1.12 (95% CI: 1.01, 1.25) with a stature of 170.5 cm compared with 164]. In contrast, risk of cortical opacification was greater in participants with higher BMIs and of taller stature, but the relation for stature diminished in magnitude and was not significant after adjustment for other risk factors. BMI was not related to risk of PSC opacities, but there was some evidence that taller stature is a risk factor for PSC opacification (P = 0.06) after adjustment for other risk factors. CONCLUSIONS: Both BMI and stature are independent risk factors for cataracts in the SEE population, with the nature of the risk dependent on cataract type. PMID- 9989687 TI - Reproducibility and validity of dietary patterns assessed with a food-frequency questionnaire. AB - BACKGROUND: Recently, the analysis of dietary patterns has emerged as a possible approach to examining diet-disease relations. OBJECTIVE: We examined the reproducibility and validity of dietary patterns defined by factor analysis using dietary data collected with a food-frequency questionnaire (FFQ). DESIGN: We enrolled a subsample of men (n = 127) from the Health Professionals Follow-up Study in a diet-validation study in 1986. A 131-item FFQ was administered twice, 1 y apart, and two 1-wk diet records and blood samples were collected during this 1-y interval. RESULTS: Using factor analysis, we identified 2 major eating patterns, which were qualitatively similar across the 2 FFQs and the diet records. The first factor, the prudent dietary pattern, was characterized by a high intake of vegetables, fruit, legumes, whole grains, and fish and other seafood, whereas the second factor, the Western pattern, was characterized by a high intake of processed meat, red meat, butter, high-fat dairy products, eggs, and refined grains. The reliability correlations for the factor scores between the 2 FFQs were 0.70 for the prudent pattern and 0.67 for the Western pattern. The correlations (corrected for week-to-week variation in diet records) between the 2 FFQs and diet records ranged from 0.45 to 0.74 for the 2 patterns. In addition, the correlations between the factor scores and nutrient intakes and plasma concentrations of biomarkers were in the expected direction. CONCLUSIONS: These data indicate reasonable reproducibility and validity of the major dietary patterns defined by factor analysis with data from an FFQ. PMID- 9989688 TI - Oral ferrous sulfate supplements increase the free radical-generating capacity of feces from healthy volunteers. AB - BACKGROUND: Most dietary iron remains unabsorbed and hence may be available to participate in Fenton-driven free radical generation in conjunction with the colonic microflora, leading to the production of carcinogens or direct damage to colonocytes. OBJECTIVE: Our aims were to measure the proportion of fecal iron available to participate in free radical generation and to determine the effect of an oral supplement of ferrous sulfate on free radical generation. DESIGN: Eighteen healthy volunteers recorded their food intake and collected fecal samples before, during, and after 2 wk of supplementation (19 mg elemental Fe/d). Total, free, and weakly chelated fecal iron were measured and free radical production was determined by using an in vitro assay with dimethyl sulfoxide as a free radical trap. RESULTS: Fecal iron increased significantly during the period of supplementation and returned to baseline within 2 wk. The concentration of weakly bound iron in feces (approximately 1.3% of total fecal iron) increased from 60 micromol/L before to 300 micromol/L during supplementation, and the production of free radicals increased significantly (approximately 40%). Higher carbohydrate diets were associated with reduced free radical generation. CONCLUSION: Unabsorbed dietary iron may increase free radical production in the colon to a level that could cause mucosal cell damage or increased production of carcinogens. PMID- 9989689 TI - Higher concentrations of serum transferrin receptor in children than in adults. AB - BACKGROUND: The serum transferrin receptor (TfR) concentration in adults is suggested to provide a sensitive measure of iron depletion and together with the serum ferritin concentration to indicate the entire range of iron status, from iron deficiency to iron overload. However, little is known about TfR concentrations in children. OBJECTIVE: Our objective was to compare serum TfR and ferritin concentrations and their ratios in children and adults and look for correlations between TfR concentrations and other measures of iron status. DESIGN: Our study groups were healthy 1-y-old infants (n = 36), 11-12-y-old prepubertal boys (n = 35), and 20-39-y-old men (n = 40). RESULTS: TfR concentrations were higher in infants (x; 95% reference interval: 7.8 mg/L; 4.5, 11.1) than in prepubertal boys (7.0 mg/L; 4.7, 9.2) and higher in prepubertal boys than in men (5.8 mg/L; 3.1, 8.5). Geometric mean TfR-ferritin ratios were higher in infants (316; 95% reference interval: 94, 1059) than in prepubertal boys (219; 78, 614) and higher in prepubertal boys than in men (72; 23, 223). By multiple linear regression analysis, the best predictors of TfR concentration were serum iron (P = 0.004) and log serum ferritin (P < 0.0001), both being inverse correlations (R2 = 0.32). Mean corpuscular volume, blood hemoglobin, transferrin iron saturation, transferrin, and even age seemed to not have an influence on the TfR concentration and erythropoiesis was not a determinant of TfR concentration. CONCLUSIONS: Low serum ferritin and iron concentrations, even within the normal physiologic range, result in high TfR concentrations. The lower the iron stores, the stronger the influence of ferritin on TfR. A high TfR concentration in children, especially in infants, is a response to physiologically low iron stores. Age-specific reference concentrations for TfR are needed. PMID- 9989690 TI - Dietary antioxidants and risk of myocardial infarction in the elderly: the Rotterdam Study. AB - BACKGROUND: Epidemiologic studies have shown dietary antioxidants to be inversely correlated with ischemic heart disease. OBJECTIVE: We investigated whether dietary beta-carotene, vitamin C, and vitamin E were related to the risk of myocardial infarction (MI) in an elderly population. DESIGN: The study sample consisted of 4802 participants of the Rotterdam Study aged 55-95 y who were free of MI at baseline and for whom dietary data assessed by a semiquantitative food frequency questionnaire were available. During a 4-y follow-up period, 124 subjects had an MI. The association between energy-adjusted beta-carotene, vitamin C, and vitamin E intakes and risk of MI was examined by multivariate logistic regression. RESULTS: Risk of MI for the highest compared with the lowest tertile of beta-carotene intake was 0.55 (95% CI: 0.34, 0.83; P for trend = 0.013), adjusted for age, sex, body mass index, pack-years, income, education, alcohol intake, energy-adjusted intakes of vitamin C and E, and use of antioxidative vitamin supplements. When beta-carotene intakes from supplements were considered, the inverse relation with risk of MI was slightly more pronounced. Stratification by smoking status indicated that the association was most evident in current and former smokers. No association with risk of MI was observed for dietary vitamin C and vitamin E. CONCLUSION: The results of this observational study in the elderly population of the Rotterdam Study support the hypothesis that high dietary beta-carotene intakes may protect against cardiovascular disease. We did not observe an association between vitamin C or vitamin E and MI. PMID- 9989691 TI - Acute effects of moderate dietary protein restriction in patients with idiopathic hypercalciuria and calcium nephrolithiasis. AB - BACKGROUND: High dietary protein intake is a potential risk factor for nephrolithiasis because of its capacity to increase urinary calcium and to facilitate lithogenesis through many other mechanisms. OBJECTIVE: Our aim was to verify the effects of moderate protein restriction in hypercalciuric patients. DESIGN: We studied 18 patients (10 men and 8 women aged 45.6+/-12.3 y) with idiopathic hypercalciuria and renal calculi. Before and after 15 d of a diet with 0.8 g protein x kg(-1) x d(-1) and 955 mg Ca, all patients were evaluated for the main serum and urinary measures of calcium metabolism as well as for urinary uric acid, oxalate, citrate, and prostaglandin E2. RESULTS: Urinary excretion of urea fell after the diet (P < 0.001). Urinary calcium (P < 0.001), uric acid (P < 0.005), oxalate (P < 0.01), and hydroxyproline (P < 0.01) decreased after protein restriction, whereas urinary citrate increased (P < 0.025). Blood pH increased after the hypoproteic diet (P < 0.05). 1,25-Dihydroxycholecalciferol (calcitriol) concentration fell significantly (P < 0.025) and parathyroid hormone increased (P < 0.001). Creatinine clearance tended to decrease (106.4+/-4.8 compared with 97.5+/-5.7 mL/min) after the diet. The decrease in urinary uric acid after the diet correlated with calcitriol concentration (r = 0.57, P < 0.05) and the decrease in urinary urea correlated positively with that in hydroxyproline excretion (r = 0.58, P < 0.01). CONCLUSIONS: In hypercalciuric patients, moderate protein restriction decreases calcium excretion, mainly through a reduction in bone resorption and renal calcium loss; both are likely due to a decreased exogenous acid load. Moreover, dietary protein restriction ameliorates the entire lithogenic profile in these patients. PMID- 9989692 TI - Serum carotenoids and tocopherols and incidence of age-related nuclear cataract. AB - BACKGROUND: It is not known whether the protective effects of antioxidants on cataract observed in experimental animals are relevant to age-related opacities in humans. OBJECTIVE: The relations of serum carotenoids and tocopherols to the incidence of age-related nuclear cataract were investigated in a random sample of 400 adults, 50-86 y of age, in the Beaver Dam Eye Study. DESIGN: Nuclear opacity was assessed by using lens photographs taken at baseline (in 1988-1990) and follow-up (in 1993-1995). Nonfasting concentrations of individual carotenoids and alpha- and gamma-tocopherol, were determined from serum obtained at baseline. A total of 252 persons were eligible for incident cataract, of whom 57 developed nuclear cataract in at least one eye. Results were adjusted for age, smoking, serum cholesterol, heavy drinking, adiposity, and, in the tocopherol models, dietary linoleic acid intake. RESULTS: Only serum tocopherol (the sum of alpha- and gamma-tocopherol, in micromol/mmol cholesterol) was associated with cataract. For total serum tocopherol, persons in tertile 3 had a lower risk of cataract than persons in tertile 1 [odds ratio (OR): 0.4; 95% CI: 0.2, 0.9; P = 0.03 for linear trend]. Although serum carotenoids were not significantly associated with nuclear cataract, marginal inverse associations with lutein (OR: 0.3; 95% CI: 0.1, 1.2; P = 0.13 for linear trend) and cryptoxanthin (OR: 0.3; 95% CI: 0.1, 1.3; P = 0.11 for linear trend) were suggested in people < or = 65 y of age. CONCLUSIONS: Findings were compatible with the possibility that nuclear cataract may be linked inversely to vitamin E status, but neither strongly supported nor negated the hypothesized inverse association of nuclear cataract with serum carotenoids. PMID- 9989693 TI - Assessment of total body stores of vitamin A in Guatemalan elderly by the deuterated-retinol-dilution method. AB - BACKGROUND: Deuterated retinol dilution (DRD) gives quantitative estimates of total body stores of vitamin A. OBJECTIVES: In elderly people, we studied 1) the time when an oral dose of deuterated vitamin A equilibrates with body stores, 2) whether serum ratios of deuterated to nondeuterated retinol (D:H) at 3 or 6 d postdosing predicted body stores, and 3) the ability of DRD to detect changes in the size of the body vitamin A pool. DESIGN: A 10-mg oral dose of [2H4]retinyl acetate was administered to 60-81-y-old Guatemalans (n = 47); percentage enrichment of serum retinol with deuterated retinol was determined at 1-3 time points per subject at 3, 6, 7, 14, 20, 21, and 54 d. In subjects from whom blood was obtained at 3 and 21 d (n = 15) and at 6 and 20 d (n = 9), total body stores were calculated by using the formula of Furr et al (Am J Clin Nutr 1989;49:713-6) with 21- or 20-d data and correlated with serum D:H at 3 or 6 d postdosing. Nine subjects received diets containing 982+/-20 microg RE (x+/-SEM) plus 800 microg RE as retinyl acetate supplements for 32 d. DRD, serum retinol, and relative dose response were used to assess vitamin A status before and after the intervention. RESULTS: Deuterated retinol equilibrated with the body pool by 20 d postdosing. Vitamin A supplementation for 32 d increased body stores, although unexplained exaggerated increases were seen in some subjects. An inverse linear relation was found between estimates of body stores and serum D:H at 3 d postdosing (r = 0.75, P = 0.002); at 6 d postdosing, the correlation was weaker. CONCLUSIONS: DRD can detect changes in total body stores of vitamin A, although factors affecting serum D:H need to be elucidated. Serum D:H 3 d postdosing might be used as an early indicator of total body stores of vitamin A, although a predictive equation will need to be developed. PMID- 9989694 TI - Maternal folate status during extended lactation and the effect of supplemental folic acid. AB - BACKGROUND: Folate requirements during lactation are not well established. OBJECTIVE: We assessed the effects of dietary and supplemental folate intakes during extended lactation. DESIGN: Lactating women (n = 42) were enrolled in a double-blind, randomized, longitudinal supplementation trial and received either 0 or 1 mg folic acid/d. At 3 and 6 mo postpartum, maternal folate status was assessed by measuring erythrocyte, plasma, milk, and dietary folate concentrations; plasma homocysteine; and hematologic indexes. Infant anthropometric measures of growth, milk intake, and folate intake were also assessed. RESULTS: In supplemented women, values at 6 mo for erythrocyte and milk folate concentrations and for plasma homocysteine were not significantly different from those at 3 mo. In supplemented women compared with unsupplemented women at 6 mo, values for erythrocyte folate (840 compared with 667 nmol/L; P < 0.05), hemoglobin (140 compared with 134 g/L; P < 0.02), and hematocrit (0.41 compared with 0.39; P < 0.02) were higher and values for reticulocytes were lower. In unsupplemented women, milk folate declined from 224 to 187 nmol/L (99 to 82 ng/mL), whereas plasma homocysteine increased from 6.7 to 7.4 micromol/L. Dietary folate intake was not significantly different between groups (380+/-19 microg/d) and at 6 mo was correlated with plasma homocysteine in unsupplemented women (r = -0.53, P < 0.01) and with plasma folate in supplemented women (r = 0.49, P < 0.02). CONCLUSIONS: A dietary folate intake of approximately 380 microg/d may not be sufficient to prevent mobilization of maternal folate stores during lactation. PMID- 9989695 TI - Umbilical vessels of preeclamptic women have low contents of both n-3 and n-6 long-chain polyunsaturated fatty acids. AB - BACKGROUND: Preeclampsia is characterized by enhanced platelet aggregation and vasoconstriction and is related to an elevated ratio of thromboxane A2 to prostacyclin I2. OBJECTIVE: We investigated whether altered eicosanoid production in preeclamptic women could be explained by the fatty acid composition of umbilical vessel walls and platelets. DESIGN: The fatty acid composition of maternal and umbilical platelets and of umbilical arteries and veins in 27 preeclamptic women and 24 normotensive women was determined. Between-group differences were analyzed with linear discriminant analysis, the Kruskal-Wallis test, or analysis of covariance with gestational age as the covariate. RESULTS: Platelets of preeclamptic women contained lower amounts of 20:5n-3 and a higher ratio of 20:4n-6 to 20:5n-3 than did platelets of normotensive women. Additionally, linear discriminant analysis revealed higher amounts of 20:4n-6 in platelets of preeclamptic women. Umbilical arteries and veins in preeclamptic women contained lower amounts of long-chain polyunsaturated fatty acids (PUFAs) of the n-3 series, n-6 long-chain PUFAs, and 20:3n-6 than did umbilical arteries and veins of normotensive women. Umbilical arteries also had lower amounts of 20:4n-6, higher amounts of 20:3n-9, and a higher ratio of 20:3n-9 to 20:4n-6. CONCLUSIONS: Low amounts of long-chain n-3 and n-6 PUFAs in umbilical vessels of preeclamptic women with adequate n-6 status may indicate insufficient transplacental transfer of long-chain PUFAs. The low amounts of 20:4n-6, high amounts of 20:3n-9, and high ratio of 20:3n-9 to 20:4n-6 in umbilical arteries may unfavorably affect local prostacyclin production. Low amounts of 20:3n-6 in umbilical arteries and veins and low amounts of 20:5n-3 in maternal platelets may contribute to the dominance of eicosanoids derived from 20:4n-6. PMID- 9989696 TI - Adjustments in energy expenditure and substrate utilization during late pregnancy and lactation. AB - BACKGROUND: Metabolic adjustments occur during pregnancy and lactation to support fetal growth and milk synthesis; however, the effect of body composition and hormonal milieu on these changes is poorly understood. OBJECTIVE: We hypothesized that energy metabolism changes during pregnancy and lactation to support fetal growth and milk synthesis, and that body composition and hormonal milieu influence these alterations. DESIGN: We measured energy expenditure, body composition, and hormone, metabolite, and catecholamine concentrations in 76 women (40 lactating, 36 nonlactating) at 37 wk gestation and 3 and 6 mo postpartum. Total energy expenditure (TEE), basal metabolic rate (BMR), sleeping metabolic rate (SMR), and minimal SMR (MSMR) were measured with room calorimetry. Fat-free mass (FFM) and fat mass were estimated with a 4-component model. RESULTS: TEE, BMR, SMR, and MSMR were 15-26% higher during pregnancy than postpartum after being adjusted for FFM, fat mass, and energy balance. TEE, SMR, and MSMR were higher in lactating than in nonlactating women. Fasting serum insulin, insulin-like growth factor I, fatty acids, and leptin, and 24-h urinary free norepinephrine, epinephrine, and dopamine correlated positively with TEE, BMR, SMR, and MSMR. In nonlactating women, the respiratory quotient decreased over time, carbohydrate oxidation decreased, and fat oxidation increased. Substrate utilization was not influenced by body composition, fasting serum hormones, or 24-h urinary catecholamines. CONCLUSIONS: These results indicate increased energy expenditure and preferential use of carbohydrates during pregnancy and lactation. Elevated respiratory quotient and carbohydrate utilization during pregnancy continue during lactation, consistent with preferential use of glucose by the fetus and mammary gland. PMID- 9989697 TI - Relation of circumferences and skinfold thicknesses to lipid and insulin concentrations in children and adolescents: the Bogalusa Heart Study. AB - BACKGROUND: Although body fat patterning has been related to adverse health outcomes in adults, its importance in children and adolescents is less certain. OBJECTIVE: We examined the relation of circumference (waist and hip) and skinfold thickness (subscapular and triceps) measurements to lipid and insulin concentrations among 2996 children and adolescents aged 5-17 y. DESIGN: This was a community-based, cross-sectional study conducted in 1992-1994. RESULTS: A central or abdominal distribution of body fat was related to adverse concentrations of triacylglycerol, LDL cholesterol, HDL cholesterol, and insulin; these associations were independent of race, sex, age, weight, and height. These associations were observed whether fat patterning was characterized by using 1) waist circumference alone (after adjustment for weight and height), 2) waist-to hip ratio, or 3) principal components analysis. Compared with a child at the 10th percentile of waist circumference, a child at the 90th percentile was estimated to have, on average, higher concentrations of LDL cholesterol (0.17 mmol/L), triacylglycerol (0.11 mmol/L), and insulin (6 pmol/L) and lower concentrations of HDL cholesterol (-0.07 mmol/L). These differences, which were independent of weight and height, were significant at the 0.001 level and were consistent across race-sex groups. CONCLUSIONS: These findings emphasize the importance of obtaining information on body fat distribution, waist circumference in particular, in children. Waist circumference, which is relatively easy to measure, may help to identify children likely to have adverse concentrations of lipids and insulin. PMID- 9989698 TI - Influence of nutritional status on the pharmacokinetics of acetylsalicylic acid and its metabolites in children with autoimmune disease. AB - BACKGROUND: It is unknown whether nutritional status associated with autoimmune disease alters the pharmacokinetics of acetylsalicylic acid (ASA) and its metabolites. OBJECTIVE: We studied the effects of the nutritional status of children with autoimmune disease on the disposition of ASA and its metabolites. DESIGN: A prospective, open-label study was performed with 21 children aged 3-15 y who required ASA therapy. Children received 25 mg ASA/kg orally. Blood samples were drawn before and 0.5, 1.0, 2.0, 4.0, 8.0, 12.0, and 24.0 h after ASA administration; urine samples were collected at different intervals. ASA and its metabolites were measured in plasma and urine. Nutritional status was assessed previously. RESULTS: The ASA maximum plasma concentration, area under the curve, and total clearance were significantly lower in underweight children than in normal-weight children. The elimination rate constants of gentisic acid (GA), salicyluric acid (SUA), and salicylic acid (SA) in plasma were slower for underweight children than for normal-weight children. The distribution volume of SUA increased significantly (r = 0.92) when the deficit percentage in weight-for height increased. Underweight children excreted less GA and SA, but more SUA, than did normal-weight children. CONCLUSIONS: These observations suggest a decrease in the hydrolysis and oxidative reactions of the metabolic pathway of ASA and its metabolites in underweight children. The study illustrates the need for pharmacokinetic data to establish the individual doses of drugs, particularly in conditions that alter nutritional status. PMID- 9989699 TI - Elevated diet-induced thermogenesis and lipid oxidation rate in Crohn disease. AB - BACKGROUND: Although malnutrition is frequently observed in Crohn disease (CD), its cause is not clear. Regulation of energy metabolism and diet-induced thermogenesis (DIT) have not been adequately studied in CD. OBJECTIVE: The aim was to study DIT and substrate oxidation in patients with inactive ileal CD. DESIGN: After a test meal providing 50.2 kJ/kg body wt, DIT was assessed by indirect calorimetry performed over 360 min in 18 CD patients and 12 healthy volunteers matched for age, sex, weight, and height. Body composition was evaluated with the labeled-water-bolus injection technique. RESULTS: Fat-free mass did not differ significantly between groups, but CD patients had markedly lower fat mass than control subjects (13.8+/-5.63 compared with 19.0+/-3.49 kg; P < 0.001). Nonprotein respiratory quotient was lower in CD patients than control subjects (0.80+/-0.04 compared with 0.86+/-0.03; P < 0.001). Average respiratory quotient between 75 and 150 min after the test meal was 0.85+/-0.03 in CD patients and 0.91+/-0.02 in control subjects (P < 0.001). Lipid oxidation rate was higher in CD patients than in control subjects (2.26+/-1.13 compared with 1.50+/-0.75 kJ/min; P < 0.05). DIT was higher in CD patients than in control subjects (9.89+/-1.93% compared with 5.67+/-0.91% of energy intake; P < 0.001). CONCLUSIONS: Patients with inactive ileal CD had significantly higher DIT and lipid oxidation rate than do healthy volunteers. These results may explain why CD patients have difficulty maintaining adequate nutritional status, and the findings also suggest that a diet relatively rich in fat may attain better energy balance. PMID- 9989700 TI - Influence of the metabolic sequelae of liver cirrhosis on nutritional intake. AB - BACKGROUND: The liver plays a central role in ingestive behavior; alterations in metabolic signaling to the brain stem as a result of chronic liver disease could influence intake. OBJECTIVE: We examined the influence of metabolic sequelae of liver disease on nutrient intake and nutritional status. DESIGN: Nutritional status and spontaneous dietary intake were examined in 65 cirrhotic patients and 14 control subjects. The response to feeding was investigated in 14 control subjects and a subgroup of 31 cirrhotic patients. Comparisons were made between patients with primary biliary cirrhosis (PBC) and hepatocellular cirrhosis (HC). RESULTS: Patients were nutritionally depleted. The fasting rate of lipid oxidation in the HC group was greater than in the control group (P < 0.01). In the fasting state, only HC patients were hyperinsulinemic [121.2+/-78.5 compared with 41.3+/-18.6 pmol/L in control subjects (P < 0.001) and 64.7+/-15.8 pmol/L in PBC patients (P < 0.05)] and this persisted during the response to feeding. In the fed state, the magnitude of change in carbohydrate oxidation was greatest in the HC group (HC: 34.6%; control: 23.1%; PBC: 25.2%). Carbohydrate and energy intakes of the HC group were lower than in control subjects (carbohydrate: 193+/ 38.3 compared with 262+/-48.1 g/d, P < 0.05; energy: 6.29+/-1.40 compared with 9.0+/-2.12 MJ/d, P < 0.05). CONCLUSIONS: Reductions in carbohydrate intake could be mediated by hyperinsulinemia and compounded by preferential uptake of carbohydrate. This may enhance gastrointestinal satiety signaling and contribute to hypophagia. PMID- 9989701 TI - Improving power with repeated measures. PMID- 9989702 TI - Nutritional status and energy metabolism in Crohn disease. PMID- 9989703 TI - My valedictory on the differences in biological potency between RRR-alpha tocopheryl and all-rac-alpha-tocopheryl acetate. PMID- 9989704 TI - Dietary determinants of iron homeostasis. PMID- 9989705 TI - So, professor, how will we die? PMID- 9989706 TI - The uses of error. PMID- 9989707 TI - New antithrombotic treatment in unstable coronary syndrome--for whom? PMID- 9989708 TI - Chronic fatigue syndrome and functional hypoadrenia--fighting vainly the old ennui. PMID- 9989709 TI - Prospects of new therapeutic approaches for Crohn's disease. PMID- 9989710 TI - Interpretation of cluster studies of tuberculosis. PMID- 9989711 TI - Review of research protocols. PMID- 9989712 TI - Effects of recombinant hirudin (lepirudin) compared with heparin on death, myocardial infarction, refractory angina, and revascularisation procedures in patients with acute myocardial ischaemia without ST elevation: a randomised trial. Organisation to Assess Strategies for Ischemic Syndromes (OASIS-2) Investigators. AB - BACKGROUND: Despite the use of heparin and aspirin, 5-10% of patients with unstable angina develop myocardial infarction or refractory angina in hospital. We tested the hypothesis that recombinant hirudin (lepirudin), a direct thrombin inhibitor, would be superior to heparin, an indirect thrombin inhibitor, in patients with acute ischaemic syndromes who were receiving aspirin. METHODS: 10,141 patients with unstable angina or suspected acute myocardial infarction without ST elevation were randomly assigned heparin (5000 units bolus then 15 units kg(-1) h(-1); n=5058) or hirudin (0.4 mg/kg bolus then 0.15 mg kg(-1) h(-1) infusion; n=5083) for 72 h in a double-blind trial. The primary outcome measure was cardiovascular death or new myocardial infarction at 7 days. Analysis was by intention to treat. FINDINGS: At 7 days, 213 (4.2%) patients in the heparin group and 182 (3.6%) in the hirudin group had experienced cardiovascular death or new myocardial infarction (relative risk 0.84 [95% CI 0.69-1.02]; p=0.077). The numbers with cardiovascular death, new myocardial infarction, or refractory angina at 7 days were 340 (6.7%) with heparin and 284 (5.6%) with hirudin (0.82 [0.70-0.96]; p=0.0125). These differences were primarily observed during the 72 h treatment period (cardiovascular death or myocardial infarction relative risk 0.76 [0.59-0.99], p=0.039: cardiovascular death, myocardial infarction, or refractory angina 0.78 [0.63-0.96], p=0.019). Although there was an excess of major bleeding requiring transfusion with hirudin (59 [1.2%] vs 34 [0.7%] with heparin; p=0.01), there was no excess in life-threatening episodes (20 in each group) or strokes (14 in each group). INTERPRETATION: The data from OASIS-2 suggest that recombinant hirudin is superior to heparin in preventing cardiovascular death, myocardial infarction, and refractory angina with an acceptable safety profile in patients with unstable angina or acute myocardial infarction without ST elevation. Thus, a direct thrombin inhibitor is more effective than an indirect thrombin inhibitor. PMID- 9989713 TI - Effectiveness of active physical training as treatment for long-standing adductor related groin pain in athletes: randomised trial. AB - BACKGROUND: Groin pain is common among athletes. A major cause of long-standing problems is adductor-related groin pain. The purpose of this randomised clinical trial was to compare an active training programme (AT) with a physiotherapy treatment without active training (PT) in the treatment of adductor-related groin pain in athletes. METHODS: 68 athletes with long-standing (median 40 weeks) adductor-related groin pain--after examination according to a standardised protocol--were randomly assigned to AT or PT. The treatment period was 8-12 weeks. 4 months after the end of treatment a standardised examination was done. The examining physician was unaware of the treatment allocation. The ultimate outcome measure was full return to sports at the same level without groin pain. Analyses were by intention to treat. FINDINGS: 23 patients in the AT group and four in the PT group returned to sports without groin pain (odds ratio, multiple logistic-regression analysis, 12.7 [95% CI 3.4-47.2]). The subjective global assessments of the effect of the treatments showed a significant (p=0.006) linear trend towards a better effect in the AT group. A per-protocol analysis did not show appreciably different results. INTERPRETATION: AT with a programme aimed at improving strength and coordination of the muscles acting on the pelvis, in particular the adductor muscles, is very effective in the treatment of athletes with long-standing adductor-related groin pain. The potential preventive value of a short programme based upon the principles of AT should be assessed in future, randomised, clinical trials. PMID- 9989714 TI - Transmission of Mycobacterium tuberculosis from patients smear-negative for acid fast bacilli. AB - BACKGROUND: The microscopic examination of sputum for acid-fast bacilli, is a simple and rapid test that is used to provide a presumptive diagnosis of infectious tuberculosis. While patients with tuberculosis with sputum smears negative for acid-fast bacilli are less infectious than those with positive smears, both theoretical and empirical evidence suggest that they can still transmit Mycobacterium tuberculosis. We aimed to estimate the risk of transmission from smear-negative individuals. METHODS: As part of an ongoing study of the molecular epidemiology of tuberculosis in San Francisco, patients with tuberculosis with mycobacterial isolates with the same DNA fingerprint were assigned to clusters that were assumed to have involved recent transmission. Secondary cases with tuberculosis, whose mycobacterial isolates had the same DNA, were linked to their presumed source case to estimate transmission from smear negative patients. Sensitivity analyses were done to assess potential bias due to misclassification of source cases, unidentified source cases, and HIV-1 co infection. FINDINGS: 1574 patients with culture-positive tuberculosis were reported and DNA fingerprints were available for 1359 (86%) of these patients. Of the 71 clusters of patients infected with strains that had matching fingerprints, 28 (39% [95% CI 28-52]) had a smear-negative putative source. There were 183 secondary cases in these 71 clusters, of whom a minimum of 32 were attributed to infection by smear-negative patients (17% [12-24]). The relative transmission rate of smear-negative compared with smear-positive patients was calculated as 0.22 (95% CI 0.16-0.32). Sensitivity analyses and stratification for HIV-1 status had no impact on these estimates. INTERPRETATION: In San Francisco, the acid-fast bacilli smear identifies the most infectious patients, but patients with smear negative culture-positive tuberculosis appear responsible for about 17% of tuberculosis transmission. PMID- 9989715 TI - Age of entry to day nursery and allergy in later childhood. AB - BACKGROUND: Infections in early childhood may prevent allergies in later life. If this hypothesis is true, early exposure to childcare outside the home would protect against atopy by promotion of cross infections. We investigated whether children who attend a nursery at a young age have a lower rate of atopy and fewer allergies than children who attend from an older age. METHODS: In a cross sectional study carried out in 1992-93, we examined 2471 children in three age groups (5-7, 8-10, and 11-14 years) from the towns of Bitterfeld, Hettstedt, and Zerbst in eastern Germany. The children's parents answered a questionnaire about allergies and symptoms, attendance at day care, and related factors. Sensitisation was assessed by skin-prick tests and measurement of allergen specific IgE antibodies in serum. FINDINGS: In 669 children from small families (up to three people), the prevalence of atopy was higher among children who started to attend day nursery at an older age than in those who started to attend at a younger age (p<0.05). Compared with children who first attended at age 6-11 months, the adjusted odds ratios for a positive skin-prick test were 1.99 (95% CI 1.08-3.66) for children who attended at age 12-23 months and 2.72 (1.37-5.40) for those who attended at age 24 months and older. In 1761 children from large families (more than three people), age of entry to day nursery had no effect on atopy. INTERPRETATION: Our findings accord with the hypothesis that early infection may protect against allergies in later life. PMID- 9989716 TI - Low-dose hydrocortisone in chronic fatigue syndrome: a randomised crossover trial. AB - BACKGROUND: Reports of mild hypocortisolism in chronic fatigue syndrome led us to postulate that low-dose hydrocortisone therapy may be an effective treatment. METHODS: In a randomised crossover trial, we screened 218 patients with chronic fatigue. 32 patients met our strict criteria for chronic fatigue syndrome without co-morbid psychiatric disorder. The eligible patients received consecutive treatment with low-dose hydrocortisone (5 mg or 10 mg daily) for 1 month and placebo for 1 month; the order of treatment was randomly assigned. Analysis was by intention to treat. FINDINGS: None of the patients dropped out. Compared with the baseline self-reported fatigue scores (mean 25.1 points), the score fell by 7.2 points for patients on hydrocortisone and by 3.3 points for those on placebo (paired difference in mean scores 4.5 points [95% CI 1.2-7.7], p=0.009). In nine (28%) of the 32 patients on hydrocortisone, fatigue scores reached a predefined cut-off value similar to the normal population score, compared with three (9%) of the 32 on placebo (Fisher's exact test p=0.05). The degree of disability was reduced with hydrocortisone treatment, but not with placebo. Insulin stress tests showed that endogenous adrenal function was not suppressed by hydrocortisone. Minor side-effects were reported by three patients after hydrocortisone treatment and by one patient after placebo. INTERPRETATION: In some patients with chronic fatigue syndrome, low-dose hydrocortisone reduces fatigue levels in the short term. Treatment for a longer time and follow-up studies are needed to find out whether this effect could be clinically useful. PMID- 9989717 TI - Tumour necrosis factor alpha and interleukin 1beta in relapse of Crohn's disease. AB - BACKGROUND: Concentrations of proinflammatory cytokines are increased in the intestinal mucosa of patients with active Crohn's disease. Experimental immunotherapeutic interventions with anticytokine agents in refractory Crohn's disease show that tumour necrosis factor alpha (TNF alpha) may be an important mediator of inflammation. We investigated the relation between production of TNF alpha and interleukin 1beta by mononuclear cells of the colonic lamina propria in patients with remitting Crohn's disease and the risk of relapse. METHODS: We followed up 137 patients with Crohn's disease in steroid-induced remission for 1 year. Secretion of proinflammatory cytokines (tumour necrosis factor alpha [TNF alpha] and interleukin 1beta) was assessed after short-term culture of human lamina propria mononuclear cells. FINDINGS: Increased secretion of TNF alpha and interleukin 1beta were predictive for acute relapses within the next year. Site and extent of disease, baseline demographics, and serum acute-phase proteins had little predictive value. INTERPRETATION: TNF alpha is important as a target molecule for immune interventions in Crohn's disease. The capacity to produce TNF alpha or interleukin 1beta may identify patients who would benefit from anti inflammatory remission maintenance. PMID- 9989718 TI - Medline solution. PMID- 9989719 TI - Risk of new AIDS diseases in people on triple therapy. PMID- 9989720 TI - Lack of sex difference in CD4 to HIV-1 RNA viral load ratio. PMID- 9989721 TI - Contraceptive potential of peptide antibiotics. PMID- 9989722 TI - Methionine homozygosity at prion gene codon 129 may predispose to sporadic inclusion-body myositis. PMID- 9989723 TI - A harmful aid to stopping smoking. PMID- 9989724 TI - Acute renal failure after ibutilide. PMID- 9989725 TI - Recapitulation of menstrual migraine with tamoxifen. PMID- 9989726 TI - Polymorphisms of paraoxonase genes and low-density lipoprotein lipid peroxidation. PMID- 9989727 TI - Verbal self-monitoring and auditory hallucinations in schizophrenia. PMID- 9989728 TI - Haemopoietic, thrombopoietic, and vascular endothelial growth factor in space. PMID- 9989729 TI - New results may help design effective HIV-1 vaccine. PMID- 9989730 TI - Alfred Cuschieri: pioneer of minimal access therapies. PMID- 9989731 TI - Time for the General Medical Council to protect UK patients. PMID- 9989732 TI - British surgeons give a warning for the future of transplant surgery. PMID- 9989734 TI - WHO reveals strategy for its "way ahead". PMID- 9989733 TI - United Nations opens gender coordinating unit for Afghanistan. PMID- 9989735 TI - Deep-vein thrombosis. AB - Deep-vein thrombosis is an important complication of several inherited and acquired disorders, but may also occur spontaneously. Prevention of recurrent venous thrombosis and pulmonary embolism is the main reason for accurate diagnosis and adequate treatment. This seminar discusses only symptomatic deep vein thrombosis. The diagnosis can be confirmed by objective tests in only about 30% of patients with symptoms. Venous thromboembolic complications happen in less than 1% of untreated patients in whom the presence of venous thrombosis is rejected on the basis of serial ultrasonography or ultrasonography plus either D dimer or clinical score. Initial anticoagulant treatment (intravenous or subcutaneous heparin) should continue until oral anticoagulant treatment, started concurrently, increases the international normalised ratio above 2.0 for more than 24 h. The optimum duration of oral anticoagulant treatment is unresolved, but may be guided by the presence of temporary or persistent risk factors or presentation with recurrent venous thromboembolism. PMID- 9989736 TI - Looking beyond the next patient: sociology and modern health care. PMID- 9989737 TI - How can medical journals help prevent poor medical research? Some opportunities presented by electronic publishing. PMID- 9989738 TI - Interferon beta treatment for multiple sclerosis. PMID- 9989739 TI - Interferon beta treatment for multiple sclerosis. PMID- 9989740 TI - Interferon beta treatment for multiple sclerosis. PMID- 9989741 TI - Interferon beta treatment for multiple sclerosis. PMID- 9989742 TI - Interferon beta treatment for multiple sclerosis. PMID- 9989743 TI - Interferon beta treatment for multiple sclerosis. PMID- 9989744 TI - Management of acute myocardial infarction. PMID- 9989745 TI - Management of acute myocardial infarction. PMID- 9989746 TI - Interferon alfa for chronic hepatitis C infection. PMID- 9989747 TI - Interferon alfa for chronic hepatitis C infection. PMID- 9989748 TI - Making sense of hepatitis C. PMID- 9989749 TI - Prospective, randomised trial of sleep deprived versus rested surgeons. PMID- 9989750 TI - Principles of epidemiological research on drug effects. PMID- 9989751 TI - Principles of epidemiological research on drug effects. PMID- 9989752 TI - Mercury in hair--but from where? PMID- 9989753 TI - Global health research and INCLEN. International Clinical Epidemiology Network. PMID- 9989754 TI - Global epidemic of cardiovascular disease. PMID- 9989755 TI - Privation and injustice in North Korea. PMID- 9989756 TI - The anomaly of Santa Rosa. PMID- 9989759 TI - The Nobel chronicles. 1937: Albert von Szent-Gyorgyi (1893-1986). PMID- 9989760 TI - Vitamin D3 derivatives (deltanoids) in the treatment of tumor cell invasion. PMID- 9989761 TI - Metabolic consequences of the West African diaspora: lessons from the thrifty gene. PMID- 9989762 TI - Pharmacology of hemoglobin therapeutics. PMID- 9989763 TI - 1alpha,25-dihydroxyvitamin D3 inhibits in vitro invasiveness through the extracellular matrix and in vivo pulmonary metastasis of B16 mouse melanoma. AB - We investigated the role of 1alpha,25-dihydroxyvitamin D3 (1alpha,25(OH)2D3) in modulating tumor cell invasiveness through the extracellular matrix (ECM) and pulmonary metastasis in B16 mouse melanoma. The pretreatment of B16 cells for 48 hours with 1alpha,25(OH)2D3 significantly inhibited in vitro invasiveness through the ECM by a mechanism that is not directly correlated with the inhibition of cell proliferation. When cells were treated with 1alpha,25(OH)2D3 for only 8 hours during the assay, no inhibitory effect was observed, suggesting that pretreatment with the hormone for more than 8 hours is necessary to inhibit the invasive potential of B16 cells. The activity of B16 cells to adhere to reconstituted basement membrane (Matrigel) and type IV collagenolysis was inhibited by pretreatment of the cells with 1alpha,25(OH)2D3 for 48 hours. Cell motility was not influenced by the hormone. Mice were inoculated subcutaneously with 3 x 106 B16 cells and were given 1alpha,25(OH)2D3 (0.5 microg/kg) or vehicle daily for 28 days, beginning 1 day after tumor inoculation. In the 1alpha,25(OH)2D3-treated group, no significant inhibition in exponential tumor growth, body weight, and serum level of calcium was observed until the twenty eighth day. The mean serum concentration of the hormone was about 50 ng/mL, and there were no significant changes in its concentration during the treatment period. In both spontaneous and experimental metastasis models of tumor-bearing mice, treatment with 1alpha,25(OH)2D3 inhibited pulmonary metastasis. These findings suggest that 1alpha,25(OH)2D3 acts on B16 cells, inhibiting invasiveness through the ECM that is caused by the inhibition of cell adhesion to the ECM and the degradation of the ECM by the cells. 1alpha,25(OH)2D3 may have the potential to inhibit metastasis by a mechanism that is not exclusively based on its anti cell proliferative effect. PMID- 9989764 TI - Serum-induced platelet procoagulant activity: an assay for the characterization of prothrombotic disorders. AB - Platelets contribute to hemostasis by forming a platelet plug and by providing a procoagulant surface for the assembly and activation of the coagulation factors. The contribution of platelets to prothrombotic disorders has been difficult to analyze. Recently an assay was reported that measured the procoagulant activity of test platelets by making the platelet lipid surface the limiting factor in the production of thrombin. In this report we describe a novel technique, based on this assay, that we used to study patient serum factors that activate control platelets and in turn initiate measurable procoagulant activity. Using this assay we investigated a group of patients with prothrombotic disorders. The patient test serum was incubated with normal platelets in the presence of activated factor Xa. The resultant thrombin was measured in a chromogenic assay. The rate limiting step was the presence of any potential platelet-activating factors, such as antibodies in the heat-treated test serum, that would allow the Xa to bind to the platelet phospholipid surface. Serum samples from patients with heparin induced thrombocytopenia (HIT) and the anti-phospholipid antibody syndrome enhanced platelet procoagulant activity, while samples from patients with idiopathic thrombocytopenic purpura and disseminated intravascular coagulation (DIC) did not. HIT serum samples also induced platelet activation, as measured by platelet microparticle shedding, carbon 14-labeled serotonin release, and platelet aggregation. The measurement of serum-induced platelet procoagulant activity provides a method for the investigation of circulating platelet agonists in prothrombotic disorders. PMID- 9989765 TI - Angiotensin II receptor blockade limits kidney injury in two-kidney, one-clip Goldblatt hypertensive rats with special reference to phenotypic changes. AB - Recent evidence indicates that tubulointerstitial injury plays an important role in hypertensive kidney injury and that phenotypic changes contribute to this pathology. Moreover, angiotensin II is known to be actively involved in the pathogenesis of progressive kidney injury induced by hypertension. The present study was undertaken to see the effect of a newly developed angiotensin II type I receptor (AT1 receptor) antagonist on hypertension-induced kidney injury and to determine the contribution of phenotypic changes to morphologic alterations. Two kidney, one-clip (2K1C), Goldblatt hypertensive rats (n = 27) were made by clipping the left renal artery. These animals were orally administered 57G709 (a selective non-peptide AT1 receptor antagonist)(10 mg/kg/day), captopril (20 mg/kg/day), or vehicle alone for 23 days beginning 4 weeks after clipping. In the non-clipped kidney of vehicle-treated 2K1 C rats, marked tubulointerstitial injury as well as glomerular sclerosis and/or hyalinosis was found in association with phenotypic changes, as shown by the neoexpression of vimentin in periglomeruli, perivascular walls, distal tubuli, and injured interstitium. Renin expression was markedly suppressed in the non-clipped kidneys of vehicle-treated 2K1C rats as compared with renin expression in normotensive control kidneys of sham-operated rats. Both 57G709 and captopril markedly ameliorated hypertensive kidney injury as reflected by the glomerular sclerosing index and by the tubulointerstitial index as determined by the point-counting method, and this improvement was accompanied by a significant decrease in blood pressure, urinary protein excretion, kidney/body weight ratio, and heart/body weight ratio. In addition, the vimentin neoexpression mentioned above was also suppressed with an inhibition of angiotensin II. These results suggest that in 2K1C Goldblatt hypertensive kidney injury, the AT1 receptor antagonist 57G709 exerts a potent renal protective effect associated with the inhibition of phenotypic changes. PMID- 9989766 TI - Activation of an iron uptake mechanism from transferrin in hepatocytes by small molecular-weight iron complexes: implications for the pathogenesis of iron overload disease. AB - The liver is one of the principal sites of iron overload in diseases such as hemochromatosis and beta thalassemia. Hence, much effort has been invested in examining the mechanisms of Fe uptake by hepatocytes. In the present study we have examined the effect of small molecular weight (M(r)) Fe complexes on Fe uptake from iron 59-labeled transferrin (Tf) and 59Fe-labeled citrate by primary cultures of hepatocytes. This was important to assess because Fe-citrate and saturated diferric Tf coexist in the serum of patients with untreated Fe overload. Preincubation of hepatocytes with the low-M(r) Fe complex ferric ammonium citrate (FAC; 25 microg/mL; (Fe) = 4.4 microg/mL) followed by incubation with 59Fe-Tf or 59Fe-citrate ((Fe) = 0.25 to 25 micromol/L) resulted in the marked stimulation of 59Fe uptake. For example, at a physiologically relevant Tf Fe concentration of 25 micromol/L, there was an 8-fold increase in 59Fe uptake by cells incubated with FAC compared to control cells. In contrast, at Tf-Fe concentrations of 0.25 to 2.5 micromol/L, 59Fe uptake in FAC-treated cells was only 1-fold to 3-fold greater than that in the corresponding controls. These data suggest that the FAC-activated Fe uptake process predominates at physiologically relevant Tf concentrations above the saturation of the Tf receptor (TfR). This is the first study to demonstrate that preincubation of hepatocytes with Iow-M(r)Fe complexes can markedly increase Fe uptake from diferric Tf. In conclusion, these results may help to explain the loading of hepatocytes with Fe that occurs in Fe overload disease despite marked down-regulation of the TfR. PMID- 9989767 TI - Increased sialylation of polymeric immunoglobulin A1: mechanism of selective glomerular deposition in immunoglobulin A nephropathy? AB - Immunoglobulin A nephropathy (IgAN) is characterized by raised serum IgA and predominant mesangial IgA deposits of polymeric nature. The abnormal glycosylation of the carbohydrate moieties in the hinge region of the IgA molecule has recently attracted much attention. In this study we investigated the galactosylation and sialylation of monomeric and polymeric IgA1 isolated from patients with IgAN. Total IgA1 in serum samples from patients with IgAN or from healthy controls was isolated with a jacalin-agarose column as jacalin-bound protein (JBP). Monomeric and polymeric IgA1 were distinctly separated by fast protein liquid chromatography. Lectin binding assays were designed to examine the sialylation and the expression of terminal galactose and N-acetyl galactosamine of the O-linked carbohydrate in the hinge region of the IgA molecule. Reduced terminal galactosylation was demonstrated in serum IgA and monomeric IgA1 isolated from patients with IgAN as compared with results in healthy control subjects. However, a reduction in terminal galactosylation was not found in polymeric IgA1 isolated from patients with IgAN. Instead, increased sialylation of IgA1 (alpha2-3 linked to galactose) was demonstrated in polymeric IgA1. This abnormality of IgA1 could bear considerable implication on the pathogenesis of IgAN, because the masking effect of sialic acid may hinder the clearance of polymeric IgA1 by the asialoglycoprotein receptor (ASGP-R) of the liver cells. An increase in the sialylated content would also render the polymeric IgA from patients with IgAN more anionic. These immunochemical properties may contribute to the selective glomerular deposition of polymeric IgA1 in IgAN. PMID- 9989768 TI - Orally administered dextran sulfate is absorbed in HIV-positive individuals. AB - Preliminary in vivo studies suggested that oral dextran sulfate was poorly absorbed, but investigations were limited by inadequate methods for measuring the drug in the body. To determine absorption in HIV-positive subjects, hydrogenated dextran sulfate, average molecular weight 8000 (Usherdex 8), was orally administered in a short-term (single dose, 4 g/day for 5 days, 7 subjects) and in a long-term study (1 g, 4 times per day for 29 to 335 days, 8 subjects), which was a continuation of the short-term study with the inclusion of an additional subject. When an agarose gel electrophoresis technique with toluidine blue staining was used, the drug was recovered from plasma (67%, peak 2.2 microg/mL) and circulating peripheral blood lymphocyte (PBL) samples (50%, peak 333 microg/L blood) obtained at 5 and 15 minutes and 1, 3, 6, and 24 hours after the first day's dose and from plasma (56%) and PBL samples (38%) obtained 5 minutes after administration on 4 subsequent days in the short-term study. In the long-term study, the drug was found in plasma (67%, peak 2.4 microg/mL) and PBL samples (25%, peak 126 microg/L blood) obtained at monthly visits within 4 hours of the last dose. The drug was found in all urine samples from all subjects in both studies (short-term study, 24-hour samples up to 4 days after the final dose; long-term study, monthly samples within 4 hours of the last dose). In the long term study, bone marrow preparations from 3 subjects showed metachromatic inclusions present in reticular cells when the cells were stained with toluidine blue, indicating the presence of sulfated polyanions. A significant rise in activated partial thromboplastin time and a drop in platelet count (P < .025) were demonstrated, with thrombocytopenia developing in 3 patients. Mild-to moderate gastrointestinal disturbances were experienced by 6 subjects in the short-term study and by all subjects in the long-term study. One subject experienced mild central nervous system symptoms in the short-term study. These results indicate that dextran sulfate is absorbed after oral administration; therefore, further studies on its efficacy, particularly in the early stages of the disease, along with additional observations on its toxicity, are warranted. PMID- 9989769 TI - Comparison of the rates of exchange of lead in the blood of newly born infants and their mothers with lead from their current environment. AB - Newly born infants (n = 15) were monitored for 6 months after birth or for longer periods to evaluate the changes in isotopic composition and lead concentration in infants as compared with that in women from the same population groups and to determine the clearance rates of lead from blood in the infants. These data represent the first published results for serial blood sampling in a relatively large cohort of newly born infants. Blood lead concentrations decrease from the cord to samples taken at 60 to 90 days and then increase by amounts varying from negligible to 166%. In spite of concern about individual susceptibility to lead pharmacokinetics, changes in isotopic ratio followed a smooth decrease over time for 9 of the 11 infants born to migrant parents, and the patterns of variation were quite reproducible. Data for 2 of 4 infants born to multigenerational Australian parents exhibited little change in isotopic ratio over time, and in the other two cases, the changes were attributed to diet. The rate of exchange (t1/2) for the migrant infants of lead in blood derived from the mother during pregnancy and the lead from the current environment was calculated by using a linear function and ranged from 65 to 131 (91+/-19, mean+/-SD) days. The half lives for the exchange of skeletal and environmental lead for 7 of the 8 women before significant mobilization of lead from the maternal skeleton ranged from 50 to 66 (59+/-6) days. One explanation for the longer half-lives for infants as compared with the mothers may be the proportionally higher contribution of current environmental (Australian) lead in the infants at parturition. Exchanges of lead in infants are more complex than for the adults, reflecting inputs from sources such as maternal skeletal lead during breast feeding. PMID- 9989770 TI - Cardioprotective effect of alpha-tocopherol, ascorbate, deferoxamine, and deferiprone: mitochondrial function in cultured, iron-loaded heart cells. AB - Because mitochondrial inner membrane respiratory complexes are important targets of iron toxicity, we used iron-loaded rat heart cells in culture to study the beneficial effect on mitochondrial enzymes of the iron chelators deferoxamine (DFO) and deferiprone (L1) and of antioxidants and reducing agents (ascorbate and alpha-tocopherol). Reduced nicotinamide adenine dinucleotide-cytochrome c oxidoreductase (complex I-III) and succinate dehydrogenase were the most sensitive indicators of iron toxicity and cardioprotective effect. Although at concentrations below 0.3 mmol/L the iron-mobilizing effect of L1 was less than that of DFO, both were equally effective in protecting or restoring mitochondrial respiratory enzyme activity. At 1.0 mmol/L, L1 toxicity was manifested in respiratory enzyme inhibition, whereas DFO had no such effect. Ascorbate (0.057 to 5.7 mmol/L) had a mild cardioprotective effect at the highest concentration only, in association with decreased cellular iron uptake. By contrast, alpha tocopherol (0.023 mmol/L) completely inhibited mitochondrial iron toxicity without affecting iron uptake or release, and irrespective of whether it was used before, during, or after in vitro iron loading. These observations illustrate the usefulness and limitations of iron chelators and other agents used for preventing iron toxicity to the heart and other vital organs, and they underline the need for exploring in more detail the effects of these agents in the clinical setting. PMID- 9989771 TI - Potential effect of the administration of substance P and allergen therapy on immunoglobulin E-mediated allergic reactions in human subjects. AB - Previously we observed and reported that immunoglobulin E-mediated (IgE-mediated) allergy in rhesus monkeys was decreased by the administration of substance P (SP) and an allergen. We extended these studies to human subjects, giving SP and 1 allergen to subjects with reactivity to more than 1 allergen, using reactivity to a second allergen as a control. SP and an allergen were initially given by aerosol delivery but subsequently were given by injection. The administration of SP and 1 allergen by aerosol delivery or injection resulted in decreased IgE mediated reactivity to the allergen administered and also to the control allergen. This result occurred in 7 of 8 human subjects. The 2 initial subjects receiving 8 SP and allergen injections had a sharp reduction in their symptoms of ragweed hay fever lasting for 3 years to date. No significant reactions to the injection of SP occurred. Further controlled human research is necessary on the administration of SP and allergen and the mechanisms of action. Unexpected and serendipitous results first observed in rhesus monkeys and reproduced in allergic human subjects provide a new and potential mechanism for control and perhaps obliteration of common IgE-mediated allergies and even more-serious allergic problems. PMID- 9989772 TI - Activation and adherence of lyophilized human platelets on canine vessel strips in the Baumgartner perfusion chamber. AB - The Baumgartner perfusion technique was used to test the ability of rehydrated lyophilized human platelets to adhere to the thrombogenic surface of a denuded arterial vessel segment and to undergo platelet activation under conditions of high shear. Twenty preparations of washed platelets were stabilized by 1-hour or 2-hour exposure to paraformaldehyde before freeze-drying in a Virtis 600 lyophilizer. The response of these fixed-dried preparations was compared with that of non-fixed platelets in fresh citrated whole blood. The outcome of each perfusion experiment was quantified in photomicrographs by morphometric estimation of the percent area of the vessel segment covered by adherent platelets after immunofluorescent staining with monoclonal antibodies to glycoprotein Ib (CD42) or glycoprotein IIbIIIa (CD41a). Evidence of activation in nonadherent platelets was examined by flow cytometry for CD62 and GP53 expression. In addition, thromboxane B2 was measured by radioimmunoassay as an index of platelet responsiveness to activation conditions during perfusion. The percent vessel coverage observed with lyophilized platelets in recombined whole blood was somewhat less than that of platelets in fresh whole blood (39% vs 73%, respectively). In other perfusion experiments performed with non-denuded vessel segments, the percent coverage was reduced by half or more for both types of platelet preparation. Scanning electron microscopy confirmed that the lyophilized platelets did not adhere to areas of intact endothelium. Furthermore, the lyophilized platelets showed a small-but-significant rise in CD62 or CD63 activation antigen expression and generated thromboxane B2 at about one third the rate of fresh platelets in these perfusion experiments. The thromboxane generation during perfusion was inhibited in fresh or lyophilized platelet preparations by pretreatment with indomethacin or PGE-1. We interpret these data as evidence of the ability of our lyophiilized platelet preparations to respond at least partially to physiologic stimuli and to adhere to appropriate thrombogenic sites to support hemostasis. PMID- 9989773 TI - Immunocytochemical localization of latent transforming growth factor-beta1 activation by stimulated macrophages. AB - Transforming growth factor-beta1 (TGF-beta) is secreted in a latent form consisting of mature TGF-beta noncovalently associated with its amino-terminal propeptide, which is called latency associated peptide (LAP). Biological activity depends upon the release of TGF-beta from the latent complex following extracellular activation, which appears to be the key regulatory mechanism controlling TGF-beta action. We have identified two events associated with latent TGF-beta (LTGF-beta) activation in vivo: increased immunoreactivity of certain antibodies that specifically detect TGF-beta concomitant with decreased immunoreactivity of antibodies to LAP. Macrophages stimulated in vitro with interferon-gamma and lipopolysaccharide reportedly activate LTGF-beta via cell membrane-bound protease activity. We show through dual immunostaining of paraformaldehyde-fixed macrophages that such physiological TGF-beta activation is accompanied by a loss of LAP immunoreactivity with concomitant revelation of TGF beta epitopes. The induction of TGF-beta immunoreactivity colocalized with immunoreactive betaglycan/RIII in activated macrophages, suggesting that LTGF beta activation occurs on the cell surface. Confocal microscopy of metabolically active macrophages incubated with antibodies to TGF-beta and betaglycan/RIII prior to fixation supported the localization of activation to the cell surface. The ability to specifically detect and localize LTGF-beta activation provides an important tool for studies of its regulation. PMID- 9989774 TI - Lamin A is part of the internal nucleoskeleton of human erythroleukemia cells. AB - Nuclear lamins are the most abundant components of the nuclear lamina, a 10-50-nm thick fibrous layer underlying the inner nuclear envelope membrane. Nevertheless, a number of recent investigations performed on epithelial and fibroblast cells have suggested that nuclear lamins are also present within the nucleoplasm and could be important constituents of the nucleoskeleton. We have studied the subnuclear distribution of lamins A and B1 in human erythroleukemia cells by using immunoblotting analysis and immunofluorescent staining of fractionated nuclei. In intact cells and isolated nuclei, antibodies to lamins A and B1 mainly stained the nuclear periphery, although some immunoreactivity was detected in the nuclear interior. However, when chromatin was removed by nuclease digestion and extraction with nonionic detergent or solutions of high ionic strength, a previously masked immunoreactivity for lamin A, but not for lamin B1, became evident in the internal part of the residual structures representing the nuclear matrix or scaffold. Preferential localization of lamin A to the inner part of the nucleus was also demonstrated by the presence of the majority of lamin A in the solubilized inner nuclear network subfraction. In contrast, lamin B1 was mainly recovered in the fraction corresponding to the nuclear periphery. Double labeling experiments showed that lamin A, but not lamin B1, colocalized with coiled and GATA-1 bodies. Thus, our results support the hypothesis that lamin A, but not lamin B1, may be a component of an internal nucleoskeleton in human erythroleukemia cells. PMID- 9989775 TI - Efficacy and specificity of antisense laminin chain-specific expression vectors in blocking laminin induction by TGFbeta1: effect of laminin blockade on TGFbeta1 mediated cellular responses. AB - Transforming growth factorbeta1 (TGFbeta1) elicits a multitude of cellular responses from the epithelial-derived human colon cancer Moser cells. TGFbeta1 induces the expression of laminin and fibronectin, and previous studies show that the induction of fibronectin is functionally associated with the regulation of carcinoembryonic antigen (CEA) expression by TGFbeta1 (Huang and Chakrabarty, 1994, J Biol Chem 269:28764-28768). In this study we constructed antisense laminin chain-specific expression vectors and determined their efficacy in blocking the expression and the induction of the large multichain laminin molecule by TGFbeta1. We also determined the functional role of laminin in several TGFbeta1-mediated responses: growth inhibition, downmodulation of anchorage-independent growth, and cellular invasion. Expression of either antisense laminin chain A, B1, or B2 RNA resulted in a downmodulation of endogenous laminin mRNA expression and blocked the induction of laminin protein by TGFbeta1 without affecting the induction of other adhesion molecules such as fibronectin or CEA. It is concluded that antisense RNA directed to only one of the laminin chains was sufficient to disrupt the induction of the complex laminin molecule in quite a specific manner. Expression of antisense laminin RNA downregulated cellular adhesion to extracellular matrix (ECM) laminin and blocked the ability of TGFbeta1 to upmodulate adhesion to ECM laminin. Expression of antisense laminin RNA, however, did not alter the downregulating effect of TGFbeta1 on cellular proliferation, anchorage-independent growth, or cellular invasion, suggesting that the induction of laminin did not play a significant functional role in these TGFbeta1-mediated cellular responses. It is likely that other adhesion pathways may be involved in mediating the action of TGFbeta1 in this cell line. PMID- 9989776 TI - Comparative effects of TGFbeta on proliferation of 7- and 14-day-old chick embryo fibroblasts and lack of involvement of the ODC/PA system in the TGFbeta signaling pathway. AB - The growth regulatory activity of transforming growth factor beta (TGFbeta) on chick embryo skin fibroblasts was compared in two developmental ages, days 7 and 14. The time course of 3H-thymidine incorporation, an S-phase marker of replication, was determined during 36 hr of TGFbeta treatment. Seven-day-old cells showed a prereplicative phase of 6 hr, and 14-day-old cells showed a prereplicative phase of 12 hr. DNA synthesis peaked at 24 hr in 7-day-old fibroblasts and was 10 times higher than that in 14-day-old fibroblasts. Ornithine decarboxylase (ODC) activity and content of the natural polyamines spermine (Spm), spermidine (Spd), and putrescine (Put) differed during cell cycle. ODC activity peaked at 12 hr in 7-day-old cells and at 6 hr in 14-day-old cells. Its level was two times higher at day 7 and was associated with a greater content of ODC mRNA. The maximum of polyamine (PA) concentration was determined after 12 hr of treatment in 7-day-old cells and after 36 hr in 14-day-old cells. These findings indicate that the TGFbeta proliferative response of embryo fibroblasts changes during development and is associated with activation of the ODC/PA system. Cotreatment with alpha-difluoromethylornithine, an enzyme activated irreversible inhibitor of ODC, did not reduced growth rate. Inhibition of ODC resulted in levels of Put and Spd comparable to that of quiescent fibroblasts, whereas Spm concentration remained higher. Because an altered ODC metabolism does not convey the effects of TGFbeta on DNA synthesis, the ODC/PA system may not play a role in the pathway of TGFbeta signaling. PMID- 9989777 TI - Calpain and calpastatin regulate neutrophil apoptosis. AB - The average polymorphonuclear neutrophil (PMN) lives only a day and then dies by apoptosis. We previously found that the calcium-dependent protease calpain is required for apoptosis in several mouse models of cell death. Here we identify calpain, and its endogenous inhibitor calpastatin, as regulators of human neutrophil apoptosis. Cell death triggered by the translation inhibitor cycloheximide is calpain-dependent, as evidenced using either a calpain active site inhibitor (N-acetyl-leucyl-leucyl-norleucinal) or agents that target calpain's calcium binding sites (PD150606, PD151746). No significant effect on cycloheximide-triggered apoptosis was found by using inhibitors of the proteasome or of other papain-like cysteine proteases, providing further evidence that the active site calpain inhibitor prevents apoptosis via its action on calpain. In addition, we find that potentiation of calpain activity by depleting its endogenous inhibitor, calpastatin, is sufficient to cause apoptosis of neutrophils. Nevertheless, apoptosis signalled via the Fas antigen proceeds regardless of the presence of calpain inhibitor. These experiments support a growing body of work, indicating an upstream regulatory role for calpain in many, but not all, forms of apoptotic cell death. They also identify calpastatin as a participant in apoptotic cell death and suggest that for at least one cell type, a decrease in calpastatin is a sufficient stimulus to initiate calpain-dependent apoptosis. PMID- 9989778 TI - Decrease in protein tyrosine phosphorylation is associated with F-actin reorganization by retinoic acid in human endometrial adenocarcinoma (RL95-2) cells. AB - Transformed cells often express elevated levels of tyrosine-phosphorylated proteins. Inhibition of protein tyrosine kinases causes reversion of malignant cells to the normal phenotype. In the present study, we evaluated the possibility that the reversion of human endometrial adenocarcinoma RL95-2 cells to a stationary phenotype induced by retinoic acid was associated with inhibition of tyrosine phosphorylation of cellular proteins. We found that retinoic acid decreased the levels of tyrosine-phosphorylated proteins, as assessed by immunostaining and immunoprecipitations using specific anti-phosphotyrosine antibodies. In addition, the inhibitors of tyrosine kinases herbimycin A and tyrphostin mimicked retinoic acid, inducing F-actin reorganization and increasing the size of RL95-2 cells, as determined by measurement of cell perimeters. Because focal adhesions that connect actin filaments with the plasma membrane are major sites of tyrosine phosphorylation, we further investigated whether selected focal adhesion proteins were affected by retinoic acid. We found that retinoic acid altered the localization of focal adhesion kinase. All-trans retinoic acid was effective in reducing the levels of focal adhesion kinase and paxillin protein. Thirteen-cis retinoic acid increased the levels of vinculin protein in the cytosolic fraction of cells. These changes are consistent with actin reorganization and reversion toward a stationary phenotype induced by retinoic acid in endometrial adenocarcinoma RL95-2 cells. Our results indicate that the differentiating effects of retinoids on endometrial cells are associated with decreases in tyrosine phosphorylation and changes in the levels and distribution of focal adhesion proteins. These findings suggest that signaling pathways that involve tyrosine kinases are potential targets for drug design against endometrial cancer. PMID- 9989779 TI - Constitutive muscarinic receptors are involved in the growth and differentiation of friend erythroleukemia cells. AB - Binding experiments with the specific muscarinic ligand [3H]N-methylscopolamine (3H-NMS) have shown the presence of constitutive muscarinic acetylcholine receptors (mAChR) on Friend murine erythroleukemia cells (MELC). Competition experiments with a panel of specific antagonists indicated that the mAChR were predominantly of the M3 subtype. This was confirmed by the rt-PCR analysis of mRNA levels for M1-M5 AChR. Uninduced MELC expressed approximately 2,100 and 1,200 binding sites per cell of growing and resting populations, respectively. The dissociation constant (K(D)) for 3H-NMS was in the picomolar range. The modulation of mAChR upon induction suggested that MELC growth and maturation might be under control of a cholinergic system since mAChR were markedly decreased or virtually absent in MELC induced to terminal division by dimethyl sulfoxide (DMSO) or hexamethylene bisacetamide (HMBA), respectively. In turn, the number of mAChR on MELC committed to polyploidization by colcemid was either increased over or maintained at the control levels when receptor densities were expressed per cell or surface unit (square micrometers), respectively. Moreover, the muscarinic agonist carbachol was found to inhibit MELC differentiation by decreasing by approximately 35% the amount of benzidine-positive (B+) cells in HMBA-induced cultures and, to a lesser degree, also AChE levels. The carbachol effect on erythroid differentiation was reverted by atropine that was found to restore the original amount of B+ cells, while it reduced acetylcholinesterase (AChE) to levels of approximately 66% of control. Such a selective atropine mediated inhibition of AChE expression was observed also in HMBA-induced MELC supplemented with the antagonist. These results have suggested that mAChR on MELC are functional and might play a role in modulating the expression of either the erythroid or megakaryocytic traits of these cells. PMID- 9989780 TI - Regulation of the high-affinity H+/peptide cotransporter in renal LLC-PK1 cells. AB - Di- and tripeptides and peptide mimetics such as beta-lactam antibiotics are efficiently reabsorbed from the tubular lumen by a high-affinity peptide transporter. We have recently identified and characterized this H+-coupled high affinity peptide transport system in the porcine proximal tubular cell line LLC PK1. Here we describe for the first time the regulation of the renal high affinity peptide cotransporter at the cellular level. Uptake of 5 microM 3H-D-Phe L-Ala into LLC-PK1 cells was significantly increased by lowering [Ca2+]in and decreased by increasing [Ca2+] in. Moreover, it was shown that the [Ca2+]in effects on peptide transport activity were dependent on Ca2+ entry from the extracellular site (e.g., via a store-regulated capacitative Ca2+ influx). Protein kinase C (PKC) was found to transmit the effects of [Ca2+]in on peptide transport. Although we demonstrate by pHin measurements that the PKC inhibitor staurosporine did decrease the transmembrane H+ gradient and consequently should have reduced the driving force for peptide uptake, the only effect on transport kinetics of 3H-D-Phe-L-Ala observed was a significant decrease in Km from 22.7+/ 2.5 microM to 10.2+/-1.9 microM with no change in maximal velocity. PMID- 9989781 TI - Non-transferrin-bound iron uptake in Belgrade and normal rat erythroid cells. AB - Belgrade (b) rats have an autosomal recessive, microcytic, hypochromic anemia. Transferrin (Tf)-dependent iron uptake is defective because of a mutation in DMT1 (Nramp2), blocking endosomal iron efflux. This experiment of nature permits the present study to address whether the mutation also affects non-Tf-bound iron (NTBI) uptake and to use NTBI uptake compared to Tf-Fe utilization to increase understanding of the phenotype of the b mutation. The distribution of 59Fe2+ into intact erythroid cells and cytosolic, stromal, heme, and nonheme fractions was different after NTBI uptake vs. Tf-Fe uptake, with the former exhibiting less iron into heme but more into stromal and nonheme fractions. Both reticulocytes and erythrocytes exhibit NTBI uptake. Only reticulocytes had heme incorporation after NTBI uptake. Properly normalized, incorporation into b/b heme was approximately 20% of +/b, a decrease similar to that for Tf-Fe utilization. NTBI uptake into heme was inhibited by bafilomycin A1, concanamycin, NH4Cl, or chloroquine, consistent with the endosomal location of the transporter; cellular uptake was uninhibited. NTBI uptake was unaffected after removal of Tf receptors by Pronase or depletion of endogenous Tf. Concentration dependence revealed that NTBI uptake into cells, cytosol, stroma, and the nonheme fraction had an apparent low affinity for iron; heme incorporation behaved like a high-affinity process, as did an expression assay for DMT1. DMT1 serves in both apparent high-affinity NTBI membrane transport and the exit of iron from the endosome during Tf delivery of iron in rat reticulocytes; the low-affinity membrane transporter, however, exhibits little dependence on DMT1. PMID- 9989782 TI - Endothelial cell apoptosis in capillary network remodeling. AB - We hypothesized that the regulation of apoptosis is an important determinant of capillary network structure. Using human umbilical vein endothelial cells (HUVEC) in in vitro model systems of capillary tube formation, we initially documented that apoptosis is a prominent feature of network formation. Perturbations of integrin-matrix signaling by the administration of either colchicine or an anti alpha(v)beta3 antibody resulted in the dissolution of the tubular network in association with increased apoptosis. The activation of the alpha(v)beta3 integrin induced increased expression of the anti-apoptotic gene bcl-2 and conferred resistance to the proapoptotic effect of TGF-beta1. In contrast to the stable networks formed by HUVEC, bovine aortic endothelial cells (BAEC) exhibited a more dynamic process of network formation and spontaneous involution. The inhibition of BAEC apoptosis by stable transfection of bcl-2 prevented the involution of the network. We hypothesized that TGF-beta1 present within the model system mediated network involution by inducing BAEC death. Indeed, blockade of TGF-beta1 with neutralizing antibodies reduced BAEC apoptosis and preserved the network structure. As observed with HUVEC networks, stable BAEC networks formed during blockade of TGF-beta1 were also dependent on the survival-promoting effects of matrixintegrin interactions. This study suggests that capillary network structure is determined by the balance of proapoptotic vs. anti-apoptotic signals mediated by the engagement of cytokine and integrin receptors within the milieu. PMID- 9989783 TI - Expression of transcripts for cysteine-rich secretory proteins (CRISPs) in the murine lacrimal gland. AB - Cysteine-rich secretory proteins (CRISPs) represent a family of evolutionarily conserved proteins which may play a role in the innate immune system and are transcriptionally regulated by androgens in several tissues. Transcripts for all three members of the CRISP family have now been identified in the murine lacrimal gland. RT-PCR using primers able to discriminate between the related CRISP forms allowed the amplification of fragments with the expected length. DNA sequencing revealed a complete identity with the hitherto characterized epididymal CRISP-1, testicular CRISP-2, and salivary gland CRISP-3. An analysis of several mouse strains indicated that all expressed the three CRISP forms, but in differing amounts. RT-PCR analysis of RNA isolated from acinar cells of lacrimal glands revealed that they expressed CRISP-1 and CRISP-2. Semiquantitative and quantitative analyses furthermore showed higher CRISP-1 and CRISP-3 mRNA levels in the lacrimal glands of male BALB/c and NOD mice when compared to females. Testosterone treatment of C3H/HeJ female mice was followed by an upregulation of the steady-state CRISP-1 but not CRISP-2 transcript levels. A comparable stimulation was observed for the mRNAs coding for parotid secretory protein (PSP), a factor previously shown to exhibit sexual dimorphism in the murine lacrimal gland. The expression of CRISP transcripts in the lacrimal gland is consistent with a function in the innate immune system. PMID- 9989784 TI - SP-A as a cytokine: surfactant protein-A-regulated transcription of surfactant proteins and other genes. AB - Pulmonary surfactant is a mixture of phospholipids and surfactant-associated proteins made by alveolar type II cells that is necessary for normal lung function. Surfactant secretion and reuptake by type II cells are regulated in part by interaction of surfactant protein-A (SP-A) with a specific receptor (SPAR) on type 11 cells. Several chemicals and hormones affect both surfactant secretion and also surfactant gene expression, but consequences of SP-A-SPAR interaction beyond regulating surfactant secretion and reuptake are unknown. Accordingly, we studied the effects of SP-A on surfactant protein gene transcription, mRNA levels, and transcript stability. SP-A elicited new transcription of surfactant proteins SP-A, SP-B, and SP-C and SPAR and c-Jun but had no effect on beta-actin or c-fos transcription. Antibody against SP-A receptor blocked SP-A-induced transcription, confirming that these actions of SP A were receptor-mediated. SP-A effects on overall transcript levels were more complex. However, SP-A, SP-B, and SP-C mRNA levels doubled in SP-A-treated cells compared to controls. SP-A is known to stabilize surfactant, control its secretion and reuptake by type II cells, and augment host antimicrobial defenses. These data indicate that SP-A also acts as an autocrine cytokine: it binds its receptor and specifically regulates transcription of surfactant proteins and other genes. PMID- 9989785 TI - Cloning and expression of a rat Smad1: regulation by TGFbeta and modulation by the Ras/MEK pathway. AB - A new family of signaling intermediates for TGFbeta superfamily members and other growth factors has recently been identified and termed Smads. It has been suggested that the Smad1 subfamily is regulated primarily by the TGFbeta superfamily member bone morphogenetic protein (BMP). Here we demonstrate that TGFbeta induced phosphorylation of endogenous Smad1 in untransformed IECs and that the RI and RII TGFbeta receptors were detectable in Smad1 immunocomplexes. Expression of a dominant-negative mutant of Ras inhibited the ability of TGFbeta to phosphorylate endogenous Smad1. In a separate series of experiments, we have cloned a rat homologue of the drosophila mad gene (termed RSmad1) by screening an intestinal epithelial cell (IEC) cDNA library. By using an in vitro kinase assay with RSmad1 as the substrate, we demonstrate that the TGFbeta receptor complex can directly phosphorylate RSmad1. We show, further, that a dominant-negative mutant of MEK1 inhibited the ability of RSmad1 to induce the TGFbeta-responsive reporter p3TP-Lux in a human breast cancer cell line. Collectively, our data demonstrate that TGFbeta can regulate Smadl and that the Ras and MEK signaling components are partially required for the ability of TGFbeta to regulate Smad1. PMID- 9989786 TI - PAK2 is cleaved and activated during hyperosmotic shock-induced apoptosis via a caspase-dependent mechanism: evidence for the involvement of oxidative stress. AB - Hyperosmotic shock elicits a stress response in mammalian cells and can lead to apoptotic cell death. In the present study, we report that hyperosmotic shock can induce activation of a 36 kDa kinase detected by an in-gel kinase assay in several cell types, including mouse Balb/c 3T3 fibroblasts, and human Hep 3B and A431 cells. This 36 kDa kinase can be recognized by an antibody against the C terminal region of a family of p21Cdc42/Rac-activated kinases (PAKs) on immunoblot. Further studies with this antibody and a PAK2-specific antibody against the N-terminal region of PAK2 demonstrate that hyperosmotic shock can induce cleavage of PAK2 to generate a 36 kDa C-terminal catalytic fragment in cells. The cleavage and activation of PAK2 was found to be closely associated with both DNA fragmentation and activation of an ICE/CED-3 family cysteine protease termed caspase-3 in hyperosmotically shocked cells. Furthermore, pretreating the cells with two caspase inhibitors (Ac-DEVD-cho and Ac-YVAD-cmk) could inhibit both cleavage/activation of PAK2 and DNA fragmentation induced by hyperosmotic shock. Moreover, all these hyperosmotic shock-induced changes (i.e., activation of caspase-3, cleavage/activation of PAK2, and DNA fragmentation) in cells could be blocked by antioxidants such as ascorbic acid (vitamine C), alpha tocopherol (vitamine E), dithiothreitol, beta-mercaptoethanol, and glutathione. Taken together, our results show that PAK2 is cleaved and activated via a caspase dependent mechanism during hyperosmotic shock-induced apoptosis and suggest the involvement of antioxidant-preventable oxidative stress in inducing this process. PMID- 9989787 TI - IgG autoantibodies from bullous pemphigoid (BP) patients bind antigenic sites on both the extracellular and the intracellular domains of the BP antigen 180. AB - Bullous pemphigoid (BP) and gestational pemphigoid (PG) are subepidermal blistering disorders associated with autoantibodies directed against two components of hemidesmosomes: the BP antigen 180 (BP180) and the BP antigen 230 (BP230). Autoantibodies against the extracellular domain (ECD) of BP180 are thought to play an initiatory role in subepidermal blister formation. To characterize the targeted antigenic sites on BP180, we have assessed the reactivity of sera from BP and PG patients against eukaryotic recombinant proteins encompassing various portions of the ECD and the intracellular domain (ICD) of BP180. Twenty-two of 22 (100%) BP sera that immunoblotted BP180 in keratinocyte extracts, bound a mutant form consisting of the entire ECD of BP180, whereas only three of these 22 sera (14%) reacted against the ECD of BP180 lacking the NC16A membrane proximal region. Thirteen out of the 22 (59%) BP sera recognized the ICD of BP180. Circulating IgG from a representative BP patient that was affinity purified against the ECD of BP180 did not bind the ICD when reblotted, indicating that there was no antigenic cross-reactivity between the ECD and the ICD of BP180. Reactivity against the ICD of BP180 was further ascertained by immunofluorescence microscopy studies showing that nine of the 22 (41%) BP sera stained COS-7 cells expressing the ICD of BP180. Using deletion mutants of the ICD of BP180, the majority of the sera was found to recognize the central region of the ICD of BP180. Specifically, an immunodominant region was localized to an 87-amino acid segment located towards the NH2-terminus of BP180. In contrast to BP sera, five of six (83%) PG sera contained IgG that recognized exclusively the NC16A region, whereas none bound to the ICD of BP180. Together, the results indicate that in BP, autoantibody reactivity to BP180 is not exclusively restricted to the NC16A region, but that additional antigenic determinants exist on the ICD of BP180. The observed heterogeneous immune response against BP180 might reflect intramolecular epitope spreading. Because the ICD ofBP180 harbors functionally important regions, it is possible that autoantibodies against the ICD of BP180 have pathogenic significance for the progression of the disease. PMID- 9989788 TI - Bullous pemphigoid sera that contain antibodies to BPAg2 also contain antibodies to LABD97 that recognize epitopes distal to the NC16A domain. AB - IgG antibodies from the sera of some patients with bullous pemphigoid (BP) react with a 180 kDa protein termed BPAg2. Antibodies in BP are directed to an extracellular noncollagenous domain of this protein termed NC16A. Our group has recently shown that a portion of the extracellular domain of BPAg2 is identical to LABD97 on the basis of amino acid sequencing. We evaluated sera from 33 patients with BP with circulating IgG antibodies on indirect immunofluorescence, which stained the epidermal side of split skin with titers ranging from 1:40 to 1:640. Immunoblotting was performed against (i) two preparations of proteins from epidermal extract, one containing BPAg2 and one containing LABD97, and (ii) the recombinant NC16A domain of the BPAg2 protein. Twelve sera reacted with the BPAg2 protein. Ten of these also reacted strongly with the NC16A domain. Nine of the 12 sera also reacted with the LABD97 antigen. Bound antibodies were eluted from the 97 kDa band and reapplied to split skin where they bound to the epidermal side. The eluted antibodies also reacted to the BPAg2 protein from the epidermal extract, but did not react with the NC16A domain on immunoblot. We conclude that these nine sera react with an epitope present within BPAg2 and LABD97 but not within the NC16A domain. This epitope is therefore distal to the previously described epitopes in BP. In BP, epitope spreading may occur and antibodies may be produced that recognize the distal portion of the BPAg2 molecule identical to LABD97 but that do not involve the NC16A domain. PMID- 9989789 TI - Human autoantibodies against HD1/plectin in paraneoplastic pemphigus. AB - Paraneoplastic pemphigus (PNP) is an autoimmune blistering disease that occurs in association with underlying neoplasms. PNP patients develop characteristic autoantibodies directed against multiple antigens, mostly identified as members of the plakin family of cytoplasmic proteins (desmoplakin I and II, bullous pemphigoid antigen I, envoplakin, and periplakin). HD1/plectin, another member of the plakin family, has not previously been detected in the characteristic PNP antigen complex, which may relate to practical difficulties associated with its large size (molecular weight approximately 500 kDa). In this study, a combination of immunoprecipitation and immunoblot is used to demonstrate that HD1/plectin is also recognized by sera from PNP patients. Thirteen of 16 PNP sera tested were positive for HD1/plectin compared with none of 43 control sera (11 pemphigus vulgaris, 11 pemphigus foliaceus, 11 bullous pemphigoid, and 10 normal individuals). Combined with our recent finding that desmoglein 3 and desmoglein 1 are cell surface target antigens in PNP, this demonstration of plectin/HD1 as another component of the antigen complex in PNP confirms that PNP is an autoimmune disease against desmoglein and plakin family molecules. PMID- 9989790 TI - Retinoid signaling by all-trans retinoic acid and all-trans retinoyl-beta-D glucuronide is attenuated by simultaneous exposure of human keratinocytes to retinol. AB - Retinol and retinyl esters are converted with time to slowly increasing amounts of all-trans retinoic acid (RA) in cultured human keratinocytes. Exogenous RA has been shown to limit retinol oxidation and to increase retinol esterification. Because significant amounts of retinol are present in biologic systems, we examined whether RA and all-trans-retinoyl-beta-D-glucuronide (RAG) interact with retinol in exhibiting their activities on HaCaT keratinocytes maintained in a retinoid-free culture system. RA was more potent than RAG and retinol in inducing ultrastructural changes attributed to retinoids, inhibiting cell proliferation as well as enhancing keratin 19 expression. In addition, retinoids were able to induce cellular retinoic acid-binding protein II mRNA levels in the cultures, whereas early RA and late RAG activity was detected. The described biologic effects of RA and RAG were diminished by simultaneous cell exposure to retinol. HaCaT cells quickly metabolized retinol to retinyl esters and consequently to low amounts of RA. RA treatment led to an early high peak of cellular RA followed by reduction to trace amounts. Treatment with RAG resulted in constantly high cellular RAG and low RA levels. Under the combined RA and retinol treatment retinyl esters were increased and RA was reduced in HaCaT cells, whereas extracellular RA levels were similar to those obtained by RA alone. On the other hand, the combination of RAG and retinol resulted in higher extracellular RAG, similar cellular RAG, and lower cellular RA levels than those obtained by RAG alone without any change in retinyl esters. This study demonstrates that retinoid signaling by RA and RAG is attenuated by simultaneous exposure of HaCaT keratinocytes in vitro to retinol. The presence of retinol in the medium alters the rate of RA or RAG metabolism and thus cellular RA concentrations. The intensity of retinoid signal is probably dependent on cellular RA levels. The resulting "antagonism" among retinoids is consistent with the presence of an auto regulatory mechanism in human keratinocytes offering protection against excessive accumulation of cellular RA. PMID- 9989791 TI - Clustering of activating mutations in c-KIT's juxtamembrane coding region in canine mast cell neoplasms. AB - The proto-oncogene c-KIT encodes a growth factor receptor, KIT, with ligand dependent tyrosine kinase activity that is expressed by several cell types including mast cells. c-KIT juxtamembrane coding region mutations causing constitutive activation of KIT are capable of transforming cell lines and have been identified in a human mast cell line and in situ in human gastrointestinal stromal tumors, but have not been demonstrated in situ in neoplastic mast cells from any species. To determine whether c-KIT juxtamembrane mutations occur in the development of mast cell neoplasms, we examined canine mastocytomas, which are among the most common tumors of dogs and which often behave in a malignant fashion, unlike human solitary mastocytomas. Sequencing of c-KIT cDNA generated from tumor tissues removed from seven dogs revealed that three of the tumors contained a total of four mutations in an intracellular juxtamembrane coding region that is completely conserved among vertebrates. In addition, two mutations were found in three mast cell lines derived from two additional dogs. One mutation from one line matched that found in situ in one of the tumors. The second was found in two lines derived from one dog at different times, indicating that the mutation was present in situ in the animal. All five mutations cause high spontaneous tyrosine phosphorylation of KIT. Our study provides in situ evidence that activating c-KIT juxtamembrane mutations are present in, and may therefore contribute to, the pathogenesis of mast cell neoplasia. Our data also suggest an inhibitory role for the KIT juxtamembrane region in controlling the receptor kinase activity. PMID- 9989792 TI - Staphylococcal toxins augment specific IgE responses by atopic patients exposed to allergen. AB - Microbial agents are known to play a significant role in aggravating allergic diseases. Recently described viral and bacterial superantigens represent one important strategy by which infectious agents can stimulate the immune response. In previous work, we reported that the staphylococcal toxin toxic shock toxin-1 (TSST-1), a prototypic superantigen, induces in vitro total IgE synthesis after cross-linking T and B cells. This study was carried out to establish a potential link between superantigens and the enhanced IgE response to specific allergens in allergic patients. Peripheral blood mononuclear cells from atopic patients were isolated during and outside the pollen allergen season and stimulated with TSST 1, a prototypic superantigen. Total IgE and interferon-gamma production were measured in supernatants of these cultures. Outside the pollen season, TSST-1 significantly increased total IgE production only in the presence of exogenous interleukin-4, whereas during the pollen season IgE production was significantly enhanced without the need of exogenous interleukin-4. This increase in the absence of exogenous interleukin-4 was associated with significantly lower interferon-gamma production by peripheral blood mononuclear cells stimulated by TSST-1 during the pollen season. Moreover, TSST-1 stimulation of peripheral blood mononuclear cells from inhalant allergic patients was followed by an increased production of allergen-specific IgE that was restricted to the allergen to which the patient was allergic and recently exposed. In addition, TSST-1 induced on B cells the expression of B7.2, a molecule that has recently been demonstrated to enhance T helper 2 responses and to be involved in IgE regulation. This study, by demonstrating that superantigens can augment allergen-specific IgE synthesis and B7.2 expression, provides a mechanism by which microbial superantigens may modulate allergic responses. PMID- 9989793 TI - NC1 domain of type VII collagen binds to the beta3 chain of laminin 5 via a unique subdomain within the fibronectin-like repeats. AB - Type VII collagen, the major component of anchoring fibrils, consists of a central collagenous triple-helical domain flanked by two noncollagenous, globular domains, NC1 and NC2. Approximately 50% of the molecular mass of the molecule is consumed by the NC1 domain. We previously demonstrated that NC1 binds to various extracellular matrix components including a complex of laminin 5 and laminin 6 (Chen et al, 1997a). In this study, we examined the interaction of NC1 with laminin 5 (a component of anchoring filaments). Both authentic and purified recombinant NC1 bound to human and rat laminin 5 as measured by enzyme-linked immunosorbant assay and by binding of 125I-radiolabeled NC1 to laminin 5-coated wells, but not to laminin 1 or albumin. NC1 bound predominantly to the beta3 chain of laminin 5, but also to the gamma2 chain when examined by a protein overlay assay. The binding of 125I-NC1 to laminin 5 was inhibited by a 50-fold excess of unlabeled NC1 or de-glycosylated NC1, as well as a polyclonal antibody to laminin 5 or a monoclonal antibody to the beta3 chain. In contrast, the NC1 laminin 5 interaction was not affected by a monoclonal antibody to the alpha3 chain. Using NC1 deletion mutant recombinant proteins, a 285 AA (residues 760 1045) subdomain of NC1 was identified as the binding site for laminin 5. IgG from an epidermolysis bullosa acquisita serum containing autoantibodies to epitopes within NC1 that colocalized with the laminin 5 binding site inhibited the binding of NC1 to laminin 5. Thus, perturbation of the NC1-laminin 5 interaction may contribute to the pathogenesis of epidermolysis bullosa acquisita. PMID- 9989794 TI - Identification of novel and known mutations in the genes for keratin 5 and 14 in Danish patients with epidermolysis bullosa simplex: correlation between genotype and phenotype. AB - Epidermolysis bullosa simplex (EBS) is a group of autosomal dominant inherited skin diseases caused by mutations in either the keratin 5 (K5) or the keratin 14 (K14) genes and characterized by development of intraepidermal skin blisters. The three major subtypes of EBS are Weber-Cockayne, Koebner, and Dowling-Meara, of which the Dowling-Meara form is the most severe. We have investigated five large Danish families with EBS and two sporadic patients with the Dowling-Meara form of EBS. In the sporadic Dowling-Meara EBS patients, a novel K14 mutation (N123S) and a previously published K5 mutation (N176S) were identified, respectively. A novel K14 mutation (K116N) was found in three seemingly unrelated families, whereas another family harbored a different novel K14 mutation (L143P). The last family harbored a novel K5 mutation (L325P). The identified mutations were not present in more than 100 normal chromosomes. Six polymorphisms were identified in the K14 gene and their frequencies were determined in normal controls. These polymorphisms were used to show that the K14 K116N mutation was located in chromosomes with the same haplotype in all three families, suggesting a common ancestor. We observed a strict genotype-phenotype correlation in the investigated patients as the same mutation always resulted in a similar phenotype in all individuals with the mutation, but our results also show that it is not possible to predict the EBS phenotype merely by the location (i.e., head, rod, or linker domains) of a mutation. The nature of the amino acid substitution must also be taken into account. PMID- 9989795 TI - C-myb, but not B-myb, upregulates type I collagen gene expression in human fibroblasts. AB - C-myb and B-myb belong to the myb family of transcription factors. We have shown previously that c-myb is deregulated in fibroblasts from systemic sclerosis (scleroderma) patients relative to normal fibroblasts. Scleroderma fibroblasts are known to express elevated levels of collagen genes and transforming growth factor beta is known to be a pro-fibrotic cytokine and to induce transcription of type I collagen genes. We have therefore investigated the role of c-myb and B-myb in the regulation of type I collagen genes in response to transforming growth factor beta in normal human fibroblasts. We show that, in these cells, transforming growth factor beta treatment induces c-myb as well as collagen alpha1(I) and alpha2(I) gene expression, but not B-myb. Furthermore we demonstrate by cotransfection assays that c-myb can upregulate alpha1(I) and alpha2(I) collagen promoters by 6-10-fold whereas B-myb is inactive. The activity of c-myb on both type I collagen promoters requires a functional c-myb DNA binding domain suggesting a direct interaction between c-myb and these promoters. Indeed c-myb is active also on a 500 bp fragment of the alpha2(I) collagen promoter and can bind to this fragment in electrophoretic mobility shift assays. Finally, we show that anti-c-myb anti-sense treatment reduces alpha1(I) and to a lesser extent alpha2(I) collagen gene expression. These data strongly suggest that c-myb, but not B-myb, plays a direct role in the upregulation of type I collagen gene expression in response to transforming growth factor beta. PMID- 9989796 TI - Recognition of local anesthetics by alphabeta+ T cells. AB - Patients with drug allergy show a specific immune response to drugs. Chemically nonreactive drugs like, for example, local anesthetics are directly recognized by alphabeta+ T cells in an HLA-DR restricted way, as neither drug metabolism nor protein processing is required for T cell stimulation. In this study we identified some of the structural requirements that determine cross-reactivity of T cells to local anesthetics, with the aim to improve the molecular basis for the selection of alternatives in individuals sensitized to a certain local anesthetic and to better understand presentation and T cell recognition of these drugs. Fifty-five clones (52 lidocaine specific, three mepivacaine specific from two allergic donors) were analyzed. Stimulatory compounds induced a down-regulation of the T cell receptor, demonstrating that these non-peptide antigens are recognized by the T cell receptor itself. A consistent cross-reactivity between lidocaine and mepivacaine was found, as all except one lidocaine specific clone proliferated to both drugs tested. Sixteen chemically related local anesthetics (including ester local anesthetics, OH- and desalkylated metabolites) were used to identify structural requirements for T cell recognition. Each of the four clones examined in detail was uniquely sensitive to changes in the structures of the local anesthetic: clone SFT24, i.e., did not recognize any of the tested OH- or desalkylated metabolites, while the clone OFB2 proliferated to all OH metabolites and other differently modified molecules. The broadly reactive clone OFB2 allowed us to propose a model, suggesting that the structure of the amine side chain of local anesthetics is essential for recognition by the T cell receptor. PMID- 9989797 TI - IgM anti-ganglioside antibodies induced by melanoma cell vaccine correlate with survival of melanoma patients. AB - Melanoma cells express ganglioside antigens GM3, GD3, GM2, and GD2 on their surface. This study examined whether immunization with a melanoma cell vaccine induced anti-ganglioside antibody responses in melanoma patients and whether these responses were correlated with survival. Sixty-six patients who had received melanoma cell vaccine immunotherapy after surgical removal of regional metastatic melanoma were identified. Cryopreserved serum samples from these patients were used in an enzyme-linked immunsorbent assay to determine the IgM antibody levels to GM2, GD2, GM3, and GD3 prior to melanoma cell vaccine treatment and 4 wk after the first melanoma cell vaccine immunization. All antibody levels significantly increased by week 4 (p < 0.001 for all four antibodies) and all increases were significantly associated with survival (anti GD2, p < 0.001; anti-GM2, p = 0.001; anti-GD3, p < 0.001; anti-GM3, p < 0.001). Anti-tumor activity of these antibodies was proved using five representative antibody-positive sera in a complement-dependent cytotoxicity assay with cultured melanoma cell lines. These studies suggest that GM2, GD2, GM2, and GD3 expressed by melanoma cells can induce specific IgM antibodies and that high levels of these antibodies might have a beneficial impact on survival. PMID- 9989798 TI - Ultraviolet B radiation upregulates the production of macrophage migration inhibitory factor (MIF) in human epidermal keratinocytes. AB - Human epidermal cells are capable of secreting various cytokines with immunologic, inflammatory, and proliferative properties. In a previous study, by reverse transcription-polymerase chain reaction and immunohistochemical analysis, we have shown that human epidermal keratinocytes express macrophage migration inhibitory factor and identified its presence in the cytoplasm. In this study, we detected an increased serum macrophage migration inhibitory factor level by enzyme-linked immunosorbent assay after a single total-body ultraviolet B exposure in vivo, indicating that human keratinocytes respond and release this cytokine in response to ultraviolet B irradiation. Moreover, we evaluated the effect of ultraviolet B on migration inhibitory factor production in cultured human epidermal keratinocytes and epidermal sheets. The results of enzyme-linked immunosorbent assay and northern blot analyses showed that migration inhibitory factor production of cultured keratinocytes was increased by ultraviolet B exposure. During the past few years, migration inhibitory factor was found to have a variety of biologic functions, such as being essential for T cell activation and induction of inflammatory cytokines. In this context, these results should encourage further investigation on the pathophysiologic role of migration inhibitory factor in cutaneous inflammatory reactions and immune responses. PMID- 9989799 TI - Upregulation and redistribution of E-MAP-115 (epithelial microtubule-associated protein of 115 kDa) in terminally differentiating keratinocytes is coincident with the formation of intercellular contacts. AB - Microtubules are involved in the positioning and movement of organelles and vesicles and therefore play fundamental roles in cell polarization and differentiation. Their organization and properties are cell-type specific and are controlled by microtubule-associated proteins (MAP). E-MAP-115 (epithelial microtubule-associated protein of 115 kDa) has been identified as a microtubule stabilizing protein predominantly expressed in epithelial cells. We have used human skin and primary keratinocytes as a model to assess a putative function of E-MAP-115 in stabilizing and reorganizing the microtubule network during epithelial cell differentiation. Immunolabeling of skin sections indicated that E MAP-115 is predominantly expressed in the suprabasal layers of the normal epidermis and, in agreement with this observation, is relatively abundant in squamous cell carcinomas but barely detectable in basal cell carcinomas. In primary keratinocytes whose terminal differentiation was induced by increasing the Ca2+ concentration of the medium, E-MAP-115 expression significantly increased during the first day, as observed by northern and western blot analysis. Parallel immunofluorescence studies showed an early redistribution of E MAP-115 from microtubules with a paranuclear localization to cortical microtubules organized in spike-like bundles facing intercellular contacts. This phenomenon is transient and can be reversed by Ca2+ depletion. Treatment of cells with cytoskeleton-active drugs after raising the Ca2+ concentration indicated that E-MAP-115 is associated with a subset of stable microtubules and that the cortical localization of these microtubules is dependent on other microtubules but not on strong interactions with the actin cytoskeleton or the plasma membrane. The mechanism whereby E-MAP-115 would redistribute to and stabilize cortical microtubules used for the polarized transport of vesicles towards the plasma membrane, where important reorganizations take place upon stratification, is discussed. PMID- 9989800 TI - Rat preputial sebocyte differentiation involves peroxisome proliferator-activated receptors. AB - The hallmark of sebaceous epithelial cell (sebocyte) differentiation is the accumulation of fused neutral fat droplets. Very little sebocyte differentiation occurs, however, in primary or organ culture, even upon incubating with androgens, which are required for maturation in vivo. We hypothesized that sebocyte cell culture systems lack activators of the peroxisome proliferator activated receptors that are involved in adipocyte differentiation. We here report that activation of peroxisome proliferator-activated receptor gamma and alpha by their respective specific ligands, a thiazolidinedione and a fibrate, induced lipid droplet formation in sebocytes but not epidermal cells. Linoleic acid and carbaprostacyclin, both peroxisome proliferator-activated receptor delta and alpha ligand-activators, were more effective but less specific, stimulating lipid formation in both types of cells. Either was more effective than the combination of peroxisome proliferator-activated receptor gamma and alpha activation, suggesting that peroxisome proliferator-activated receptor delta is involved in this lipid formation. Linoleic acid 0.1 mM stimulated significantly more advanced sebocyte maturation than any other treatment, including carbaprostacyclin, which suggests a distinct role of long chain fatty acids in sebocyte differentiation. Peroxisome proliferator-activated receptor gammal mRNA was demonstrated in sebocytes, but not in epidermal cells; it was more strongly expressed in freshly dispersed than in cultured sebocytes. In contrast, peroxisome proliferator-activated receptor delta mRNA was expressed to a similarly high extent before and after culture in both sebocytes and epidermal cells. These findings are compatible with the concepts that peroxisome proliferator-activated receptor gamma1 gene expression plays a unique role in the differentiation of sebocytes, while peroxisome proliferator-activated receptor delta activation and long chain fatty acids finalize sebocyte maturation and are capable of stimulating epidermal lipid formation. These findings have implications for the development of new modalities of treatment for acne vulgaris. PMID- 9989801 TI - Persistent transgene expression and normal differentiation of immortalized human keratinocytes in vivo. AB - Cells transduced ex vivo with transgenes encoded on retroviruses have constant and prolonged expression in vitro; however, in vivo expression is quickly lost. Much attention has been directed at methods to circumvent this problem. We have shown that loss of transgene expression does not occur when transduced immortalized 3T3 cells are transplanted to the in vivo setting of athymic mice. Ease of acquisition and potential for clinical application led us to assess the potential of using immortalized human keratinocytes for expression of transgenes in vivo. Human keratinocytes were immortalized with a HPV16-E6/E7 retrovirus, transduced with a lacZ retrovirus, cloned by limiting dilution, seeded onto a physiologic dermal substrate, and transplanted to athymic mice. Six weeks after transplantation, the immortalized transgene expressing keratinocytes had formed an epidermis that was indistinguishable from one formed by nonimmortalized keratinocytes; furthermore, there was no loss of expression of the lacZ gene. These observations show that methods to extend cell survival are an alternative approach to achieving stable and prolonged expression of transgenes in vivo and that HPV16-E6/ E7 immortalized keratinocytes generate an epidermis with normal morphology. PMID- 9989802 TI - Urokinase is a positive regulator of epidermal proliferation in vivo. AB - The epidermis is a self-renewing tissue that must maintain a basal proliferative rate as well as respond to various perturbing stimuli. Regulation of keratinocyte proliferation involves diverse molecules, including growth factors, ions, and hormones. We recently proposed that a proteinase, urokinase-type plasminogen activator (uPA) may be added to this list, based on correlative evidence linking expression of uPA and murine epidermal hyperproliferation. Here we report that, during the first 3 d of life, the epidermis from mice that bear a targeted deletion of the uPA gene has a significantly lower proliferative rate than the epidermis from wild-type mice. In contrast, proliferation in the matrix keratinocytes of the hair follicles is not decreased in neonatal uPA-/- mice. Vertical migration of keratinocytes during terminal differentiation was not affected. We therefore conclude that lack of uPA is associated with a decrease in epidermal proliferation. PMID- 9989803 TI - Increased vibrissa growth in transgenic mice expressing insulin-like growth factor 1. AB - Insulin-like growth factor 1 (IGF-1) mediates many of the actions of growth hormone. Overexpression of IGF-1 has been reported to have endocrine and paracrine/autocrine effects on somatic growth in transgenic mice. To study the paracrine/autocrine effects of IGF-1 in hair follicles, transgenic mice were produced by pronuclear microinjection of a construct containing a mouse ultra high sulfur keratin (UHS-KER) promoter linked to an ovine IGF-1 cDNA. This UHS KER promoter has previously been shown to direct expression of a reporter gene to the hair follicles of transgenic mice. Four transgenic mouse lines were established as a result of microinjection of 435 embryos. Transgene expression was found in skin at day 8 and day 15 of age in three of the lines. Progeny tests were carried out by mating two of the transgenic expressing males to nontransgenic females. Mice from one line were all nonexpressors while four of the 12 mice from the other showed integration of the transgene and three expressed transgene IGF-1 mRNA in the skin. Vibrissa growth at 11-21 d of age was significantly greater in transgenic expressors than in their nontransgenic littermates. Specifically, the increase in vibrissa length for transgenics at days 11-16 (20.5%) is approximately 2-fold compared with days 16-21 (11.9%). These results demonstrate that local overexpression of IGF-1 in transgenic mice is capable of stimulating vibrissa growth during the first neonatal hair cycle. PMID- 9989804 TI - Evidence for superantigen involvement in skin homing of T cells in atopic dermatitis. AB - The environmental factors that contribute to the homing of T cells in skin disease is unknown. The skin lesions of atopic dermatitis (AD) are frequently colonized with superantigen (SAg), producing strains of Staphylococcus aureus. In vitro, these superantigens have the capacity to activate and expand T cells expressing specific T cell receptor BV gene segments, and also to increase their skin homing capacity via upregulation of the skin homing receptor, cutaneous lymphocyte-associated antigen (CLA). These activities have been proposed to enhance the chronic cutaneous inflammation of AD, but an in vivo role for SAg has not been conclusively demonstrated. In this study, we sought direct evidence for in vivo SAg activity by comparing the SAg profiles of S. aureus cultured from the skin of AD subjects to the T cell receptor Vbeta repertoire of their skin homing (CLA+) T cells in peripheral blood. SAg secreting S. aureus strains were identified in six of 12 AD patients, and all of these subjects manifested significant SAg-appropriate Vbeta skewing within the CLA+ subsets of both their CD4+ and their CD8+ T cells. T cell receptor Vbeta skewing was not detectable among the overall CD4+ or CD8+ T cell subsets of these subjects, and was not present within the CLA+ T cell subsets of five patients with plaque psoriasis and 10 normal controls. T cell receptor BV genes from the presumptively SAg-expanded populations of skin homing T cells were cloned and sequenced from three subjects and, consistent with a SAg-driven effect, were found to be polyclonal. We conclude that SAg can contribute to AD pathogenesis by increasing the frequency of memory T cells able to migrate to and be activated within AD lesions. PMID- 9989805 TI - IgA antibodies of cicatricial pemphigoid sera specifically react with C-terminus of BP180. PMID- 9989806 TI - Cell cycle start from quiescence controlled by tyrosine phosphorylation of Cdk4. AB - In mammals Cdk4 (or Cdk6 in some cell types) is required for starting the cell cycle. Recently we showed that Cdk4 is regulated by tyrosine phosphorylation and dephosphorylation, and that this regulation is required for a DNA damage-induced G1 arrest. We report here that a generic anti-phosphotyrosine antibody can detect tyrosine-phosphorylated Cdk4 and that as revealed by immunoblot detection and kinase assay, this regulation is employed for DNA damage-responsive checkpoint control during cell cycle start from quiescence. In rat fibroblasts traversing G1 or arrested in G1 by deprivation of anchorage, Cdk4 does not undergo tyrosine phosphorylation. Tyrosine phosphorylation occurs only during cell's arrest in quiescence and dephosphorylation during their cell cycle start. Ultraviolet irradiation blocks dephosphorylation and concomitant activation of Cdk4, thereby preventing the start of cell cycling. Thus, unlike tyrosine phosphorylation of Cdc2, which controls phase transition in the regular cell cycle, tyrosine phosphorylation of Cdk4 is employed for controlling cell cycle start from quiescence in a rat fibroblast. PMID- 9989807 TI - A rate limiting function of cdc25A for S phase entry inversely correlates with tyrosine dephosphorylation of Cdk2. AB - The cdc25A phosphatase removes inhibitory phosphates from threonine-14 and tyrosine-15 of cyclin dependent kinase-2 (cdk2) in vitro, and it is therefore widely assumed that cdc25A positively regulates cyclin E- and A-associated cdk2 activity at the G1 to S phase transition of the mammalian cell division cycle. Human cdc25A was introduced into mouse NIH3T3 fibroblasts co-expressing a form of the colony-stimulating factor-1 (CSF-1) receptor that is partially defective in transducing mitogenic signals. Cdc25A enabled these cells to form colonies in semisolid medium containing serum plus human recombinant CSF-1 in a manner reminiscent of cells rescued by c-myc. However, cdc25A-rescued cells could not proliferate in chemically defined medium containing CSF-1 and continued to require c-myc function for S phase entry. When contact-inhibited cells overexpressing cdc25A were dispersed and stimulated to synchronously enter the cell division cycle, they entered S phase 2-3 h earlier than their parental untransfected counterparts. Shortening of G1 phase temporally correlated with more rapid degradation of the cdk inhibitor p27Kip1 and with premature activation of cyclin A-dependent cdk2. Paradoxically, tyrosine phosphorylation of cdk2 increased considerably as cells entered S phase, and cdc25A overexpression potentiated rather than diminished this effect. At face value, these results are inconsistent with the hypothesis that cdc25A acts directly on cdk2 to activate its S phase promoting function. PMID- 9989808 TI - Inhibition of RNA polymerase II as a trigger for the p53 response. AB - The mechanisms by which the p53 response is triggered following exposure to DNA damaging agents have not yet been clearly elucidated. We and others have previously suggested that blockage of RNA polymerase II may be the trigger for induction of the p53 response following exposure to ultraviolet light. Here we report on the correlation between inhibition of mRNA synthesis and the induction of p53, p21WAF1 and apoptosis in diploid human fibroblasts treated with either UV light, cisplatin or the RNA synthesis inhibitors actinomycin D, DRB, H7 and alpha amanitin. Exposure to ionizing radiation or the proteasome inhibitor LLnL, however, induced p53 and p21WAF1 without affecting mRNA synthesis. Importantly, induction of p53 by the RNA synthesis or proteasome inhibitors did not correlate with the induction of DNA strand breaks. Furthermore, cisplatin-induced accumulation of active p53 in repair-deficient XP-A cells occurred despite the lack of DNA strand break induction. Our results suggest that the induction of the p53 response by certain toxic agents is not triggered by DNA strand breaks but rather, may be linked to inhibition of mRNA synthesis either directly by the poisoning of RNA polymerase II or indirectly by the induction of elongation blocking DNA lesions. PMID- 9989809 TI - Association with E2F-1 governs intracellular trafficking and polyubiquitination of DP-1. AB - The cell cycle-regulated transcription factor E2F is a family of heterodimers composed of E2F and DP protein subunits. While DP proteins stabilize DNA binding of E2F proteins, and influence the entry of E2F-4 and E2F-5 into the nucleus, the role of DP proteins in E2F-dependent gene expression is not well understood. Using immunolocalization, immunoprecipitation, and cell fractionation experiments, here we show association with E2F subunits governs intracellular trafficking and ubiquitination of DP-1. In transient transfection experiments, DP 1 polypeptides that stably bound E2F-1 entered the nucleus. DP-1 proteins that failed to associate with E2F subunits accumulated in the cell cytoplasm as polyubiquitinated DP-1. A Chinese hamster cell line that conditionally expresses HA-DP-1 was used to examine the effect of DP-1 on cell cycle progression. In serum response experiments, moderate increases in HA-DP-1 led to a threefold increase in E2F DNA binding activity in vitro, a corresponding increase in dhfr gene expression during transition of G1, and higher rates of S phase entry. However, flow cytometry showed cells expressing very high levels of HA-DP-1 failed to enter the S phase. Inhibition of cell cycle progression by high levels of HA-DP-1 was associated with the accumulation of other ubiquitinated cellular proteins, including c-jun and the cyclin-dependent kinase inhibitor p21, indicating that degradation of ubiquitinated proteins is required for progression from G0 to S phase even in the presence of activated E2F. Under similar conditions, expression of E2F-1 reduced the levels of ubiquitinated cellular proteins and accelerated cell cycle progression. Our studies indicate association with E2F subunits prevents ubiquitin-dependent degradation of DP-1 in the cytoplasm by promoting nuclear entry of E2F/DP heterodimers. PMID- 9989810 TI - The bovine papillomavirus type 1 E6 oncoprotein sensitizes cells to tumor necrosis factor alpha-induced apoptosis. AB - Expression of viral proteins may result in susceptibility of cells to the cytotoxic effect of Tumor Necrosis Factor Alpha (TNF). While murine C127 cells containing the bovine papillomavirus type 1 (BPV-1) genome were reported to exhibit increased TNF sensitivity, the gene(s) responsible was not identified. The BPV-1 E6 oncoprotein induces tumorigenic transformation of murine C127 cells and stimulates transcription when targeted to a promoter. BPV-1 E6 was introduced into C127 cells (PBE6) by retroviral infection and stable clones were isolated. These cells showed increased apoptosis in response to TNF, as measured by several criteria. TNF-induced apoptosis in PBE6 cells was accompanied by increased release of arachidonic acid, indicating that phospholipase A2 was activated. We also provide evidence that BPV-1 E6 mediated-sensitization of cells to TNF induced apoptosis can occur in the absence of p53. PMID- 9989811 TI - Detection of mutations by automated fluorescence/RNA-based dideoxy fingerprinting (ARddF) AB - Dideoxy fingerprinting (ddF) is a hybrid technique which combines aspects of single strand conformational polymorphism (SSCP) and dideoxy sequencing to detect the presence of single base changes in a defined fragment of nucleic acid. ddF is no more technically demanding than SSCP, yet it is more sensitive in detecting point mutations. We describe here the adaptation of conventional ddF to an automated sequencing system using fluorescent Cy5 labeled primers. We show that automated RNA-based ddF (ARddF) has several advantages over conventional radioisotope-based ddF, including: (1) analysis of larger nucleic acid fragments (up to 10(3) bp), due to the ability to continuously analyse and compile sequencing information; (2) greater reliability for distinguishing mutant sequences from wild type sequences (particularly when the mutation leads to gain or loss of a dideoxy termination segment); (3) the use of fluorescent labeled primers, making ARddF less hazardous than methods requiring radionucleotides. The use of ARddF in conjunction with new methods for isolating RNA from a [corrected] small number of cells facilitates mutational analysis of small tissue biopsies and other limited samples, and will allow more widespread application of mutational screening in the setting of clinical diagnostic laboratories. PMID- 9989812 TI - Mutually exclusive expression patterns of Bcl-2 and Par-4 in human prostate tumors consistent with down-regulation of Bcl-2 by Par-4. AB - Par-4 is a widely expressed protein that sensitizes both prostatic and non prostatic cells to apoptosis. Constitutive- or regulated- overexpression of Par-4 caused a reduction in the levels of the anti-apoptotic protein Bcl-2. Replenishment of Bcl-2 levels abrogated susceptibility to Par-4-dependent apoptosis, suggesting that Par-4-mediated apoptosis requires downmodulation of Bcl-2 levels. The inverse correlation between Par-4 and Bcl-2 expression was recapitulated in human prostate tumors. Par-4 but not Bcl-2 was detected in the secretory epithelium of benign prostatic tumors and in primary and metastatic prostate cancers that are apt to undergo apoptosis. Moreover, xenografts of human, androgen-dependent CWR22 tumors showed Par-4 but not Bcl-2 expression. By contrast, androgen-independent CWR22R tumors derived from the CWR22 xenografts showed mutually exclusive expression patterns of Par-4 and Bcl-2. These findings suggest a mechanism by which Par-4 may sensitize prostate tumor cells to apoptosis. PMID- 9989813 TI - Deregulation of NPM and PLZF in a variant t(5;17) case of acute promyelocytic leukemia. AB - Greater than 95% of acute promyelocytic leukemia (APL) cases are associated with the expression of PML-RARalpha. This chimeric protein has been strongly implicated in APL pathogenesis because of its interactions with growth suppressors (PML), retinoid signaling molecules (RXRalpha), and nuclear hormone transcriptional co-repressors (N-CoR and SMRT). A small number of variant APL translocations have also been shown to involve rearrangements that fuse RARalpha to partner genes other than PML, namely PLZF, NPM, and NuMA. We describe the molecular characterization of a t(5;17)(q35;q21) variant translocation involving the NPM gene, identified in a pediatric case of APL. RT-PCR, cloning, and sequence studies identified NPM as the RARalpha partner on chromosome 5, and both NPM-RARalpha and RARalpha-NPM fusion mRNAs were expressed in this patient. We further explored the effects of the NPM-RARalpha chimeric protein on the subcellular localization of PML, RXRalpha, NPM, and PLZF using immunofluorescent confocal microscopy. While PML remained localized to its normal 10-20 nuclear bodies, NPM nucleolar localization was disrupted and PLZF expression was upregulated in a microspeckled pattern in patient leukemic bone marrow cells. We also observed nuclear co-localization of NPM, RXRalpha, and NPM-RARalpha in these cells. Our data support the hypothesis that while deregulation of both the retinoid signaling pathway and RARalpha partner proteins are molecular consequences of APL translocations, APL pathogenesis is not dependent on disruption of PML nuclear bodies. PMID- 9989814 TI - Sequential molecular abnormalities are involved in the multistage development of squamous cell lung carcinoma. AB - To understand the molecular pathways involved in the pathogenesis of squamous cell lung carcinoma, we obtained DNA from 94 microdissected foci from 12 archival surgically resected tumors including histologically normal epithelium (n=13), preneoplastic lesions (n=54), carcinoma is situ (CIS) (n=15) and invasive tumors (n=12). We determined loss of heterozygosity (LOH) at 10 chromosomal regions (3p12, 3p14.2, 3p14.1-21.3, 3p21, 3p22-24, 3p25, 5q22, 9p21, 13q14 RB, and 17p13 TP53) frequently deleted in lung cancer, using 31 polymorphic microsatellite markers, including 24 that spanned the entire 3p arm. Our major findings are as follows: (1) Thirty one percent of histologically normal epithelium and 42% of mildly abnormal (hyperplasia/metaplasia) specimens had clones of cells with allelic loss at one or more regions; (2) There was a progressive increase of the overall LOH frequency within clones with increasing severity of histopathological changes; (3) The earliest and most frequent regions of allelic loss occurred at 3p21, 3p22-24, 3p25 and 9p21; (4) The size of the 3p deletions increased with progressive histologic changes; (5) TP53 allelic loss was present in many histologically advanced lesions (dysplasia and CIS); (6) Analyses of 58 normal and non-invasive foci having any molecular abnormality, indicated that 30 probably arose as independent clonal events, while 28 were potentially of the same clonal origin as the corresponding tumor; (7) Nevertheless, when the allelic losses in the 30 clonally independent lesions and their clonally unrelated tumors were compared the same parental allele was lost in 113 of 125 (90%) of comparisons. The mechanism by which this phenomenon (known as allele specific mutations) occurs is unknown; (8) Four patterns of allelic loss in clones were found. Histologically normal or mildly abnormal foci had a negative pattern (no allelic loss) or early pattern of loss while all foci of CIS and invasive tumor had an advanced pattern. However dysplasias demonstrated the entire spectrum of allelic loss patterns, and were the only histologic category having the intermediate pattern. Our findings indicate that multiple, sequentially occurring allele specific molecular changes commence in widely dispersed, apparently clonally independent foci, early in the multistage pathogenesis of squamous cell carcinomas of the lung. PMID- 9989815 TI - Ectopic expression of pRb2/p130 suppresses the tumorigenicity of the c-erbB-2 overexpressing SKOV3 tumor cell line. AB - We investigated the in vitro and in vivo effects of the ectopic expression of the pRb2/p130 cell cycle regulator on c-erbB-2-associated tumorigenicity. SKOV3 ovarian cancer cells, which display c-erbB-2 gene amplification and oncoprotein (p185HER2) overexpression, were stably transfected with a plasmid containing the coding sequence for human wild-type pRb2/p130 (wtRb2), or with pcDNA3 empty vector. Three wtRb2-transfected clones (cl. 24, ci. 49, cl. 100) and one empty vector-transfected clone (cl. mock) were randomly picked and further analysed. Western blot analysis revealed high levels of pRb2/p130 in the three clones compared to mock cells. Levels of p185HER2 and the extent of its tyrosine phosphorylation were similar in all transfectant clones, as were levels of pRb1 and p107. In anchorage-independent growth assays, the number of colonies from wtRb2 clone-transfectants was about 90% less than that arising from mock cells (P<0.001). Tumor take rates of the three wtRb2-transfected clones xenografted in nu/nu mice were much lower than those of mock cells, and tumor volume was decreased by 80% (P<0.001). A mutant version of pRb2/p130 deleted of the pocket region (mut-Rb2) was also transfected into SKOV3 cells and studied in parallel with the wtRb2-transfected and pcDNA empty vector-transfected bulk populations. mut-Rb2 transfected cells showed no inhibition of in vitro colony formation and were fully tumorigenic. Together, these findings indicate that Rb2 acts as a tumor suppressor gene in vivo and in vitro in SKOV3 cells and that the intact pocket region is required for the suppressor activity. PMID- 9989816 TI - Two novel regions of interstitial deletion on chromosome 8p in colorectal cancer. AB - We have investigated interstitial deletions of chromosome 8 in 70 colorectal carcinomas and 11 colonic adenomas using 11 microsatellite markers, including eight spanning the centromeric region of chromosome 8p (p11.2-p12). Allelic loss or imbalance was observed in 38 (54%) cancers and four (36%) adenomas. Twenty eight (40%) of the cancers had deletions of 8p11.2-p12. Two distinct and independent regions of interstitial loss were found within this region. Fluorescent in situ hybridization, using an alpha satellite repeat probe to the centromere of 8p and two probes to the P1 region, was performed in four tumours that demonstrated allelic imbalance. Localized heterozygous deletions were confirmed in all four tumours. Eleven (16%) cancers had localized deletion in the region ANK-1 to D8S255 (P1) and a further eleven (16%) cancers had a less well localized deletion in the region defined by the markers D8S87 to D8S259 (P2). Loss of both centromeric loci was identified in a further six (9%) tumours. A functional significance for these two deletion regions was sought by correlation with primary and secondary tumour characteristics. Isolated P2 deletion was associated with 'early' T1 cancers (2p=0.0002), and were also identified in 3/11 adenomas. Conversely, interstitial deletions of the P1 locus were more frequently seen in 'locally invasive' T3/4 cancers (2p=0.015), and isolated P1 deletions were also associated with the presence of liver metastases (2p=0.016). Our data provide evidence of at least two genes within the 8p11.2-p12 region, mutations in which may confer different and independent roles in the pathogenesis of colorectal cancer. PMID- 9989817 TI - Both AP-1 and Cbfa1-like factors are required for the induction of interstitial collagenase by parathyroid hormone. AB - PTH is a major regulator of calcium homeostasis by mobilizing calcium through bone resorption. We show that the expression of collagenase-3 (MMP-13), a member of the family of matrix metalloproteinases, required for the cleavage of collagens in the bone, is increased upon PTH injection in mice. A cis-acting element in the collagenase-3 promoter was identified which, together with AP-1, is required for induction by PTH. This element contains CCACA motifs which are required for binding of the 65 kDa osteoblast-specific splice variant of Cbfal. Introduction of mutations in this binding site that interfere with protein interaction also eliminates PTH inducibility and transactivation by Cbfa/ Runt proteins. While DNA binding activity of AP-1 is increased upon PTH treatment, high basal level of Cbfa/Runt binding activity is detectable in untreated cells which is not further increased by PTH, suggesting that AP-1 and Cbfal contribute to transcriptional activation through different mechanisms. In agreement with the critical role of both proteins defined in tissue culture cells, expression of collagenase-3 is reduced in mice lacking c-fos and is completely absent in cbfa1 /-embryos. These data provide the first evidence for a critical role of Cbfal, a major regulator of bone development, in PTH-dependent processes such as bone resorption. PMID- 9989818 TI - Rapid dephosphorylation of p107 following UV irradiation. AB - In response to UV irradiation, mouse NIH3T3 fibroblasts transiently arrest predominantly in the G1 phase of the cell cycle. Here, we investigate the role of the retinoblastoma-related pocket proteins in this biological process. We report here that UV induces an increase in p107/E2F complexes, shown previously to be repressors of E2F-dependent transcriptional activity. Several lines of evidence indicate that the increase of p107/E2F complexes following UV irradiation is a consequence of rapid dephosphorylation of p107. First, UV-mediated p107 dephosphorylation could be abolished by pretreatment of NIH3T3 fibroblasts with the serine/threonine phosphatase inhibitors calyculin A and okadaic acid. Second, alteration of protein phosphatase 2A holoenzyme composition by over-expression of specific B subunits interfered with UV-mediated dephosphorylation of p107. Consistent with this, p107 could be dephosphorylated in vitro with PP2A. Moreover, dephosphorylation of p107 was shown to be independent of the activity of p53 and p21, as it occurred also in UV-treated p53-null as well as p21-null mouse fibroblasts. We observed a close correlation between the UV dosages required for G1 cell cycle arrest and p107 dephosphorylation. Our data suggest a model in which UV radiation-induced cell cycle arrest depends, at least in part, on the induction of a PP2A-like phosphatase that acts on p107. PMID- 9989819 TI - The product of the cph oncogene is a truncated, nucleotide-binding protein that enhances cellular survival to stress. AB - Cph was isolated from neoplastic Syrian hamster embryo fibroblasts initiated by 3 methylcholanthrene (MCA), and was shown to be a single copy gene in the hamster genome, conserved from yeast to human cells, expressed in fetal cells and most adult tissues, and acting synergistically with H-ras in the transformation of murine NIH3T3 fibroblasts. We have now isolated Syrian hamster full-length cDNAs for the cph oncogene and proto-oncogene. Nucleotide sequence analysis revealed that cph was activated in MCA-treated cells by a point-mutational deletion at codon 214, which caused a shift in the normal open reading frame (ORF) and brought a translation termination codon 33 amino acids downstream. While proto cph encodes a protein (pcph) of 469 amino acids, cph encodes a truncated protein (cph) of 246 amino acids with a new, hydrophobic C-terminus. Similar mechanisms activated cph in other MCA-treated Syrian hamster cells. The cph and proto-cph proteins have partial sequence homology with two protein families: GDP/GTP exchange factors and nucleotide phosphohydrolases. In vitro translated, gel purified cph proteins did not catalyze nucleotide exchange for H-ras, but were able to bind nucleotide phosphates, in particular ribonucleotide diphosphates such as UDP and GDP. Steady-state levels of cph mRNA increased 6.7-fold in hamster neoplastic cells, relative to a 2.2-fold increase in normal cells, when they were subjected to a nutritional stress such as serum deprivation. Moreover, cph-transformed NIH3T3 cells showed increased survival to various forms of stress (serum starvation, hyperthermia, ionizing radiation), strongly suggesting that cph participates in cellular mechanisms of response to stress. PMID- 9989820 TI - Growth stimulation of murine fibroblasts by TGF-beta1 depends on the expression of a functional p53 protein. AB - Transforming Growth Factor-beta1 (TGF-beta1) inhibits the proliferation of most cells, but stimulates some mesenchymal cell types, including murine NIH3T3 fibroblasts. We show here that TGF-beta1 growth stimulation of NIH3T3 fibroblasts is reversed when these cells are transformed by SV40 or are transfected with a plasmid encoding the SV40 Large T antigen. Inversion of the TGF-beta1 growth stimulation of NIH3T3 cells is not observed when these cells are transfected with plasmids expressing either a mutant Large T, unable to bind P53, or the E1A adenovirus oncoprotein which binds the retinoblastoma protein pRB but not P53. But when the TGF-beta1-growth stimulated cells are transfected with a plasmid expressing a mutant form of Large T capable of binding to P53, but not to pRB, or with one expressing the E1B-55 kD adenovirus oncoprotein, which also binds to P53 but not to pRB, the cells are growth-inhibited by TGF-beta1. The cdk inhibitor p21Waf is decreased in TGF-beta1-stimulated NIH3T3 fibroblasts and increased in TGF-beta1-inhibited SV40-transformed cells. Finally, we show that T12 fibroblasts, from a P53 knockout mouse, are growth inhibited by TGF-beta1 and that they remain so upon transfection with a P53 which is mutant at restrictive temperature, but become growth-stimulated by this factor at permissive temperature when P53 is functional. These data strongly suggest that growth stimulation of fibroblasts by TGF-beta1 depends on the presence of a functional P53 protein and that inversion of this response occurs if P53 is absent or inactivated. PMID- 9989821 TI - Bcl-2 interferes with the execution phase, but not upstream events, in glucocorticoid-induced leukemia apoptosis. AB - Due to their growth arrest- and apoptosis-inducing ability, glucocorticoids (GC) are widely used in the therapy of various lymphoid malignancies. Cell death is associated with activation of members of the interleukin-1beta-converting enzyme (ICE) protease/caspase family and, is presumably prevented by the anti-apoptotic protein Bcl-2. To further address the role of Bcl-2 in GC-mediated cytotoxicity, we generated subclones of the GC-sensitive human T-cell acute lymphoblastic leukemia line CCRF-CEM, in which transgenic Bcl-2 expression is regulated by tetracycline. Up to about 48 h, exogenous Bcl-2 almost completely protected these cells from apoptosis, digestion of poly-ADP ribose polymerase (PARP) and generation of Asp-Glu-Val-Asp cleaving (DEVDase) activity. However, when the cells were cultured for another 24 h in the continuous presence of GC, they underwent massive apoptosis that was associated with DEVDase activity and PARP cleavage. Bcl-2 did not markedly affect GC-mediated growth arrest, thereby separating the anti-proliferative from the apoptosis-inducing effect of GC. Moreover, Bcl-2 did not prevent the dramatic reduction in the levels of several mRNAs observed during GC treatment, including the transgenic Bcl-2 mRNA. Thus, Bcl-2 can be placed upstream of effector caspase activation, but downstream of other GC-regulated events, such as growth arrest and the potentially critical repression of steady state levels of multiple mRNA. PMID- 9989822 TI - Characteristics of genomic breakpoints in TLS-CHOP translocations in liposarcomas suggest the involvement of Translin and topoisomerase II in the process of translocation. AB - Fusion of TLS/FUS and CHOP gene by reciprocal translocation t(12;16)(q32;q16) is a common genetic event found in myxoid and round-cell liposarcomas. Characterization of this genetic event was performed by three methods, Southern blot, RT-PCR, and genomic long-distance PCR in nine myxoid and three round-cell liposarcomas. All but one tumors showed genetic alternations indicating the fusion of TLS/FUS and CHOP gene. Two novel types of fusion transcripts were found, of which one lacked exon 2 sequence of CHOP gene, and the other lacked 3' half of exon 5 of TLS gene. The latter case was caused by a cryptic splicing site which was created by the genomic fusion. Detailed analyses genomic fusion points revealed several sequence characteristics surrounding the fusion points. Homology analyses of breakpoint sequences with known sequence motifs possibly involve in the process of translocation uncovered Translin binding sequences at both of TLS/ FUS and CHOP breakpoints in two cases. Translocations were always associated with other genetic alterations, such as deletions, duplications, or insertions. Short direct repeats were almost always found at both ends of deleted or duplicated fragments some of which had apparently been created by joining of sequences that flank the rearrangement. Finally, consensus topoisomerase II cleavage sites were found at breakpoints in all cases analysed, suggesting a role of this enzyme in creating staggered ends at the breakpoint. These data suggested that sequence characteristics may play an important role to recruit several factors such as Translin and topoisomerase II in the process of chromosomal translation in liposarcomas. PMID- 9989823 TI - Augmentation of a humanized anti-HER2 mAb 4D5 induced growth inhibition by a human-mouse chimeric anti-EGF receptor mAb C225. AB - Overexpression of epidermal growth factor (EGF) receptor and HER2 (p185neu) may both contribute to the growth of human cancers. A humanized anti-HER2 monoclonal antibody (mAb) 4D5 and a human-mouse chimeric anti-EGF receptor mAb C225 are currently being investigated in clinical trials for their anti-tumor activities. In the present study, we have examined the effect of concurrent treatment of OVCA 420 human ovarian cancer cells with mAb C225 and mAb 4D5. Exposure of OVCA420 cells to saturating concentrations of C225 (20 nM) for 7 days resulted in 40-50% growth inhibition, and exposure to 20 nM mAb 4D5 also resulted in 30-40% growth inhibition. The growth inhibition of OVCA420 cells by mAb C225 or 4D5 was associated with an increased G1 cell population; an increased level of a cyclin dependent kinase (CDK) inhibitor p27Kip1 with increased association of p27kip1 with CDK2, CDK4 and CDK6; and decreased activities of these CDKs. Combination treatment with concurrent exposure to mAbs C225 and 4D5 resulted in additive anti proliferative effects on these cells, which was accompanied by enhanced G1 cell distribution, a greater increase in the levels of p27Kip1 and a greater decrease in the activities of CDK kinases. The anti-proliferative effects and related changes in cell cycle regulators induced by mAb 4D5, mAb C225 or the combination of the two mAbs could be reversed by concurrent exposure to exogenous EGF. Our data suggest the potential fruitful cooperation of anti-EGF receptor mAb and anti HER2 mAb in the treatment of human cancers stimulated by EGF receptor and HER2 signals. PMID- 9989824 TI - The expression of P-glycoprotein is causally related to a less aggressive phenotype in human osteosarcoma cells. AB - The relationship between P-glycoprotein expression and malignancy is controversial. We have recently found that, in osteosarcoma, multidrug resistance (MDR) is associated with a less aggressive behavior, both in vitro and in clinical settings. In this study, we evaluated whether P-glycoprotein overexpression has a cause-effect relationship with the reduced metastatic potential of MDR cells, or rather reflects a more complex phenotype. MDR1 gene transfected osteosarcoma cell clones, showing different levels of P-glycoprotein expression, were analysed for their in vitro characteristics and their tumorigenic and metastatic ability in athymic mice. Apart from the different levels of P-glycoprotein, no significant change in the expression of surface antigens or in the differentiative features were observed in the MDR1 gene transfectants compared to the parental cell lines or control clones, obtained by transfection with neo gene alone. In contrast to controls, however, MDR1 transfectants showed a significantly lower ability to grow in semi-solid medium and were completely unable to grow and give lung metastases in athymic mice. These findings indicate that P-glycoprotein overexpression is causally associated with a low malignant potential of osteosarcoma cells, and open new insights on the role and functions of P-glycoprotein activity. PMID- 9989825 TI - Hydrogen peroxide-induced apoptosis is CD95-independent, requires the release of mitochondria-derived reactive oxygen species and the activation of NF-kappaB. AB - Reactive oxygen species (ROS) play an important role in cell death induced by many different stimuli. This study shows that hydrogen peroxide-induced apoptosis in T-cells did not require tyrosine kinase p561ck, phosphatase CD45, the CD95 receptor and its associated Caspase-8. H2O2-triggered cell death led to the induced cleavage and activation of Caspase-3. Hydrogen peroxide-treatment of T cells resulted in the formation of mitochondrial permeability transition pores, a rapid decrease of the mitochondrial transmembrane potential delta psi(m) and the release of Cytochrome C. Inhibition of the mitochondrial permeability transition by bongkrekic acid (BA), or interference with the mitochondrial electron transport system by rotenone or menadione prevented the cytotoxic effect of H2O2. Antimycin A, a mitochondrial inhibitor that increases the release of mitochondrial ROS (MiROS), enhanced apoptosis. Overexpression of Bcl-2 and the viral anti-apoptotic proteins BHRF-1 and E1B 19K counteracted H2O2-induced apoptosis. Pharmacological and genetic inhibition of transcription factor NF kappaB protected cells from hydrogen peroxide-elicited cell death. This detrimental effect of NF-kappaB mediating hydrogen peroxide-induced cell death presumably relies on the induced expression of death effector genes such as p53, which was NF-kappaB-dependently upregulated in the presence of H2O2. PMID- 9989826 TI - APS, an adaptor protein containing PH and SH2 domains, is associated with the PDGF receptor and c-Cbl and inhibits PDGF-induced mitogenesis. AB - Previously we cloned a novel adaptor protein, APS (adaptor molecules containing PH and SH2 domains) which was tyrosine phosphorylated in response to c-kit or B cell receptor stimulation. Here we report that APS was expressed in some human osteosarcoma cell lines, markedly so in SaOS-2 cells, and was tyrosine phosphorylated in response to several growth factors, including platelet derived growth factor (PDGF), insulin-like growth factor (IGF), and granulocyte macrophage colony stimulating factor (GM-CSF). Ectopic expression of the wild type APS, but not C-terminal truncated APS, in NIH3T3 fibroblasts suppressed PDGF induced MAP kinase (Erk2) activation, c-fos and c-myc induction as well as cell proliferation. In vitro binding experiments suggest that APS bound to the beta type PDGF receptor, mainly via phosphotyrosine 1021 (pY1021). Indeed, tyrosine phosphorylation of PLC-gamma, which has been demonstrated to bind to pY1021, but not that of PI3 kinase and associated proteins, was reduced in APS transformants. PDGF induced phosphorylation of the tyrosine residue of APS close to the C terminal end. In vitro and in vivo binding experiments indicate that the tyrosine phosphorylated C-terminal region of APS bound to c-Cbl, which has been shown to be a negative regulator of tyrosine kinases. Since coexpression of c-Cbl with wild type APS, but not C-terminal truncated APS, synergistically inhibited PDGF induced c-fos promoter activation, c-Cbl could be a mechanism of inhibitory action of APS on PDGF receptor signaling. PMID- 9989827 TI - Surface plasmon resonance measurements reveal stable complex formation between p53 and DNA polymerase alpha. AB - Surface plasmon resonance measurements were used for detecting and quantifying protein-protein interactions between the tumor suppressor protein p53, the SV40 large T antigen (T-ag), the cellular DNA polymerase alpha-primase complex (pol prim), and the cellular single-strand DNA binding protein RPA. Highly purified p53 protein bound to immobilized T-ag with an apparent binding constant of 2 x 10(8) M(-1). Binding of p53 to RPA was in the same order of magnitude with a binding constant of 4 x 10(8) M(-1), when RPA was coupled to the sensor chip via its smallest subunit, and 1 x 10(8) M(-1), when RPA was coupled via its p70 subunit. Furthermore, p53 bound human DNA polymerase alpha-primase complex (pol prim) with a K(A) value of 1 x 10(10) m(-1). Both the p68 subunit and the p180 subunit of pol-prim could interact with p53 displaying binding constants of 2 x 10(10) m1(-1) and 5 X 10(9) M(-1), respectively. Complex formation was also observed with a p180/p68 heterodimer, and again with a binding constant similar. Hence, there was no synergistic effect when p53 bound to higher order complexes of pol-prim. A truncated form of p53, consisting of amino acids 1-320, bound pol prim by four orders of magnitude less efficiently. Therefore, an intact C terminus of p53 seems to be important for efficient binding to pol-prim. It was also tried to measure complex formation between p53, pol-prim, and T-ag. However there was no evidence for the existence of a ternary complex consisting of T-ag, pol-prim, and p53. PMID- 9989828 TI - Distinct chromosomal alterations associated with TP53 status of LoVo cells under PALA selective pressure: a parallel with cytogenetic pathways of colorectal cancers. AB - This study investigates the chromosomal alterations involved in the acquisition of PALA resistance of LoVo colorectal cancer cells homozygous for wild-type TP53 before and after transfection with a 143Ala-mutated TP53 gene. PALA resistance was always associated with an increased number of CAD gene copies, but gene amplification sensu stricto was rarely observed. Interestingly, distinct chromosome patterns were found in relation to the TP53 status of the cells. In parental LoVo cells, the CAD copy number was increased through gains of normal chromosome 2 whereas in transfectant clones, resistance mostly occurred through chromosome rearrangements. The relationship with the two different cytogenetic patterns described in colorectal tumors is discussed. PMID- 9989829 TI - Co-amplification and overexpression of CDK4, SAS and MDM2 occurs frequently in human parosteal osteosarcomas. AB - Amplification of genes in the 12q13-15 region occurs frequently in several malignancies including osteosarcoma. The products of these amplified genes are thought to provide cancer cells with a selective growth advantage; however, the specific gene(s) driving this amplicon is unknown. We have previously shown that the SAS gene is amplified in most parosteal osteosarcomas. In this study we analysed additional putative growth regulatory genes in this chromosomal region in 24 primary osteosarcoma specimens. CDK4 and SAS were coamplified in 6/6 parosteal tumors, and MDM2 was also amplified in 4/5 parosteal cases. In comparison, amplification occurred in only 2/16 classical intramedullary osteosarcomas and involved the SAS gene. Each amplified gene had a correspondingly elevated mRNA level. Four high grade intramedullary tumors had elevated mRNA expression of SAS, but did not exhibit gene amplification. Gene amplification/overexpression was not associated with metastatic disease and did not change markedly with tumor progression, as evidenced by analysis of sequential tumor specimens from eight patients. Three other genes in the 12q13-15 region (CDK2, WNT1 and WNT10b) were not amplified in any of the tumors. The different patterns of gene amplification and overexpression of CDK4, SAS and MDM2 in parosteal and intramedullary osteosarcomas may help explain the disparity in the biological behaviour of these two types of osteosarcoma. PMID- 9989830 TI - High frequency of p16INK4A gene alterations in hepatocellular carcinoma. AB - The tumor suppressor gene p16 (CDKN2/MTS-1/INK4A) is an important component of the cell cycle and inactivation of the gene has been found in a variety of human cancers. In order to investigate the role of p16 gene in the tumorigenesis of hepatocellular carcinoma (HCC), 48 cases of HCC were analysed for p16 alterations by: methylation-specific PCR (MSP) to determine the methylation status of the p16 promoter region; comparative multiplex PCR to detect homozygous deletion; PCR SSCP and DNA sequencing analysis to identify mutation of the p16 gene. We found high frequency of hypermethylation of the 5' CpG island of the p16 gene in 30 of 48 cases (62.5%) of HCC tumors. Moreover, homozygous deletion at p16 region were present in five of 48 cases (10.4%); and missense mutation were detected in three of 48 cases (6.3%). The overall frequency of p16 alterations, including homozygous deletion, mutation and hypermethylation, in HCC tumors was 70.8% (34 of 48 cases). These findings suggest that: (a) the inactivation of the p16 is a frequent event in HCC; (b) the p16 gene is inactivated by multiple mechanisms including homozygous deletion, promoter hypermethylation and point mutation; (c) the most common somatic alteration of the p16 gene in HCC is de novo hypermethylation of the 5' CpG island; and (d) in contrast to other studies, high frequency of genomic alterations are not uncommon in the 9p21 of the p16 gene. Our results strongly suggest that the p16 gene plays an important role in the pathogenesis of HCC. PMID- 9989831 TI - Mechanism of activation of Pak1 kinase by membrane localization. AB - Pak kinases are a family of serine/threonine protein kinases homologous to Ste20p of yeast. Paks can be activated in vivo and in vitro by binding to GTP-bound Cdc42 and Rac1, members of the Rho family of small GTPases implicated in regulating the organization of the actin cytoskeleton. We have previously reported that the SH2/SH3-containing adaptor protein Nck binds Pak kinase through its second SH3 domain. Pak1 can be targeted to the membrane by Nck in response to tyrosine phosphorylation, and membrane association of Pak1 is sufficient to increase its specific activity. The mechanism whereby Pak is activated by membrane localization, however, is unknown. We show here that expression of three proteins that inhibit Rho-family GTPases by different mechanisms (RhoGDI, Bcr and D57Y Cdc42) all block the activation of Pak by a membrane-targeted Nck SH3 domain, demonstrating that the in vivo activation of Pak1 induced by membrane localization is dependent on Rho-family GTPases. This implies that Pak activity can be regulated in cells both by the level of GTP loading of various Rho-family GTPases and the local concentration of Pak relative to these GTPases. Our data also suggest the existence of Rho-family GTPases in addition to Cdc42 and Rac1 that can activate Pak on membranes. PMID- 9989832 TI - Reduced growth rate and transformation phenotype of the prostate cancer cells by an interferon-inducible protein, p202. AB - Interferons (IFNs) can exert cytostatic and immunomodulatory effects on carcinoma cells. In particular, growth inhibition of human prostate carcinoma by IFNs has been demonstrated both in vitro and in vivo. p202 is a 52 kd nuclear phosphoprotein known to be induced by IFNs. In this report, we showed that the expression of p202 was associated with an anti-proliferative effect on human prostate cancer cells. More importantly, cells that expressed p202 showed reduced ability to grow in soft-agar, indicating a loss of transformation phenotype. Our data suggest that p202 is a growth inhibitor gene in prostate cancer cells and its expression may also suppress transformation phenotype of prostate cancer cells. PMID- 9989833 TI - Constitutive activation of the 41-/43-kDa mitogen-activated protein kinase signaling pathway in human tumors. AB - The 41-kDa and 43-kDa mitogen-activated protein (MAP) kinases play a pivotal role in the mitogenic signal transduction pathway and are essential components of the MAP kinase cascade, which includes MAP kinase kinase (MEK) and Raf-1. As aberrant activation of signal transducing molecules such as Ras and Raf-1 has been linked with cancer, we examined whether constitutive activation of the 41-/43-kDa MAP kinases is associated with the neoplastic phenotype of 138 tumor cell lines and 102 primary tumors derived from various human organs. Constitutive activation of the MAP kinases was observed in 50 tumor cell lines (36.2%) in a rather tissue specific manner: cell lines derived from pancreas, colon, lung, ovary and kidney showed especially high frequencies with a high degree of MAP kinase activation, while those derived from brain, esophagus, stomach, liver and of hematopoietic origin showed low frequencies with a limited degree of MAP kinase activation. We also detected constitutive activation of the 41-/43-kDa MAP kinases in a relatively large number of primary human tumors derived from kidney, colon and lung tissues but not from liver tissue. Many tumor cells, in which point mutations of ras genes were detected, showed constitutive activation of MAP kinases, however, there were also many exceptions to this observation. In contrast, the activation of the 41-/43-kDa MAP kinases was accompanied by the activation of Raf-1 in the majority of tumor cells and was completely associated with the activation of MEK and p90rsk in all the tumor cells examined. These results suggest that the constitutive activation of 41-/43-kDa MAP kinases in tumor cells is not due to the disorder of MAP kinases themselves, but is due to the disorder of Raf-1, Ras, or some other signaling molecules upstream of Ras. PMID- 9989834 TI - Localization of a novel tumor suppressor gene associated with human oral cancer on chromosome 4q25. AB - Recent cytogenetic and molecular studies with highly polymorphic microsatellite markers have implicated allele loss involving chromosome 4 in several human cancers, which suggests the presence of multiple tumor suppressor gene (TSG) loci. However, there has been no detailed analysis of loss of heterozygosity (LOH) on chromosome 4 in oral squamous cell carcinoma (OSCC). To determine the location of a putative TSG associated with OSCC on chromosome 4, polymerase chain reaction (PCR) analysis of microsatellite polymorphisms corresponding to 17 loci was performed to screen 32 patients with OSCC. LOH was observed in the majority of the tumors (75%) in at least one of the loci. The loci on the long arm exhibited a significantly higher frequency of deletions (66%) than those of the short arm (25%). Among the loci tested, frequent LOH was centered at D4S1573 on 4q25, which represents a region of about 4 centimorgans (cM). However, no commonly deleted regions were found on the short arm of the chromosome. We detected microsatellite instability (MI) in 31% of the cases. MI was also observed more frequently on the long arm (28%) than the short arm (6%). Thus, our data indicate that alterations of chromosome 4 regions, especially the long arm, are associated with OSCC tumorigenesis and that the 4q25 region may harbor at least one putative TSG. PMID- 9989835 TI - Differential gene expression in neoplastic and human papillomavirus-immortalized oral keratinocytes. AB - We have previously demonstrated that normal human oral keratinocytes immortalized by transfection with human papillomavirus type-16 Dna became tumorigenic after exposure to a chemical carcinogen. In an effort to detect differentially regulated genes associated with this transition from the immortal to the malignant phenotype, we employed representational differences analysis (a PCR coupled subtractive hybridization technique). After analysing 50 colonies, 12 putative messages were identified. Northern analysis comparison using the identified cDNAs as probes was made between normal human oral keratinocyte, papillomavirus-immortalized human oral keratinocytes (HOK-16B), a neoplastic cell line derived from HOK-16B (HOK-16B-BaP-T) and the human oral cancer cell lines Hep-2, SCC-9 and Tu-177. We found that mRNAs encoding for cyclophilin A, c-myc binding protein 1, the heat shock protein 90alpha and one unknown transcript were up-regulated in the oral cancer cell lines analysed as well as in HOK-16B cells. We also detected a downregulation of the mRNAs encoding the skin-derived antileukoproteinase SKALP/elafin, the translationally regulated p23 protein and one unknown transcript. Whether these messages are associated to the neoplastic conversion of human keratinocytes remains to be determined. PMID- 9989836 TI - A frequent activated smoothened mutation in sporadic basal cell carcinomas. AB - Basal-cell carcinomas (BCCs) are the most common cancer in Caucasians. It has been reported that the patched gene is inactivated in 30-40% sporadic BCCs and 20% sporadic medulloblastomas via loss of heterozygosity and nonsense mutations. Recently, two activating smoothened mutations have been found in the sporadic basal cell carcinomas. One, at base pair 1604 (G-to-T transversion) of exon 9, changes codon 535 from tryptophan to leucine, and the other, at base pair 1685 (G to-A transition) of exon 10, changes codon 562 from arginine to glutamine (Xie et al., 1998). In our study, 1604G-->T was found in 20 out of 97 (20.6%) sporadic BCCs. The high prevalence indicates that 1604G is the mutation hot spot in our tumor samples. This mutation was detected in all three histological subtypes of BCCs, suggesting that smoothened mutation is an early event during the development of the tumor. Our finding of a high smoothened mutation rate, together with high frequent patched gene mutations reported recently, indicates that activation of the hedgehog signal transduction pathway is the most common and early event in the development of sporadic BCCs. Additionally, to determine whether smoothened, like patched, is also involved in the carcinogenesis of medulloblastomas, we screened medulloblastoma samples for these two mutations by restriction analysis. We have found the 1604G-->T mutation in 1 out of 21 medulloblastomas. This result confirmed smoothened gene involvement in the carcinogenesis of medulloblastoma. PMID- 9989837 TI - Linkage between melanocytic tumor development and early burst of Ret protein expression for tolerance induction in metallothionein-I/ret transgenic mouse lines. AB - We examined the basis of the all or none difference in inducing melanocytic tumor development among three transgenic mouse lines (304, 192 and 242) to which the same promoter-enhancer (metallothionein-I) and oncogene (ret) were introduced. We initially demonstrated that both skin melanosis and Ret protein expression in skin, thymus and brain first became detectable before or immediately after birth in the mice of the tumor developing lines (304 and 192), whereas they became detectable a few days after birth in the mice of the non-tumor developing line (242) by Western blotting and immunohistochemical analysis. Interestingly, the Ret protein expression in skin developed rapidly after birth as a burst with peak levels on 0.5-1.5 day newborns of lines 304 and 192 and on 7.0-7.5 day-old mice of line 242. The levels of autophosphorylation of Ret kinase in skin were, however, invariable among these three transgenic mouse lines. The mice of line 242, but not those of lines 192 and 304, responded to Ret protein immunization by increased antigen-dependent lymphocyte proliferation and T-cell-mediated tumor growth suppression in vitro. Furthermore, ret-transgenic mice of line 242, but not line 304, rejected the subcutaneously transplanted tumors that had originally developed in a mouse of line 304. These results suggest that whether oncogene product-specific-tolerance is established or not to antitumor immunity may be decided by the dynamics of ret oncogene expression before and after delivery and this is the primary factor determining development or non-development of melanoma. PMID- 9989838 TI - Different regulation of c-Myc- and E2F-1-induced apoptosis during the ongoing cell cycle. AB - The transcription factors c-Myc and E2F-1 have been shown to harbour both mitogenic and apoptotic properties. Both factors have been implicated in the regulation of the transition from the G1 phase to the S phase in the mammalian cell cycle. However, whether cell death triggered by these molecules is dependent on the cell's position in the ongoing cell cycle remained elusive. Using centrifugal elutriation we here show for the first time that c-Myc induces apoptosis in G1 and in G2 phase, whereas E2F-1-induced apoptosis specifically occurs in G1. S phase cells are resistant to cell death triggered by these factors. We demonstrate that this is not a general phenomenon, since S phase cells are susceptible to apoptosis induced by treatment with actinomycin D and to the anti-apoptotic activity of Bcl-2. Our data indicate that S phase cells harbour specific protective activities against c-Myc- and E2F-1-induced apoptosis. Our results demonstrate that these transcription factors, although probably sharing specific apoptotic pathways, also take distinct routes to induce cell death and that apoptosis can occur at different phases of the cell cycle depending on the apoptotic stimulus. In this report we present the usefulness of a new approach to determine the regulation of apoptosis in the ongoing unperturbated cell cycle. This approach has clear implications for the identification of target genes involved in the regulation of cell death. PMID- 9989839 TI - CD4+ CD56+ cutaneous neoplasms: a distinct hematological entity? Groupe Francais d'Etude des Lymphomes Cutanes (GFELC). AB - We report seven cases of particular cutaneous tumors selected from the register of the French Study Group on Cutaneous Lymphomas. The patients (three men, four women) were aged 37-86 years. They initially presented with cutaneous nodules or papules. Three cases presented with regional lymph nodes. Stagings were negative, except for one patient with bone marrow involvement. Histological features were relevant with pleomorphic medium T-cell lymphoma, but these cells exhibited a distinguishing phenotype. They were positive for CD4, CD56, and also CD45, CD43, and HLA-DR. All other T-cell and B-cell markers were negative. The myelomonocytic markers (CD13, CD14, CD15, CD33, CD117, myeloperoxidase, and lysozyme) were negative excepted CD68, which was clearly positive in four cases and weakly in two cases. Others natural killer cell markers (CD16, CD57, TiA1, granzyme B), TdT, and CD34 were negative. Polymerase chain reaction studies did not detect any B or T clonal rearrangement. The cytogenetic studies, performed in five cases, showed a del(5q) in two cases. All patients were treated successfully by polychemotherapy, but relapsed quickly in the skin, between 4 and 28 months. Five patients developed bone marrow involvement, with leukemia in three cases, and they died in 5-27 months. One patient died at 17 months with skin progression. The seventh patient is alive at 33 months, with cutaneous progression. The origin of these cells is unclear. Despite expression of CD4 or CD56, we failed to demonstrate a T-cell, natural killer cell origin. However, CD4 and CD56 are not specific for T or natural killer lineages. Although these two markers are also known to be expressed by monocytic cells, classic myeloid antigens were negative. These seven cases, together with other rare similar cases already reported, seem to represent a distinct entity likely developed from hematological precursor cells. PMID- 9989840 TI - Rare expression of high-molecular-weight cytokeratin in adenocarcinoma of the prostate gland: a study of 100 cases of metastatic and locally advanced prostate cancer. AB - Immunohistochemistry with antibodies for high-molecular-weight cytokeratin labels basal cells and is used as an ancillary study in diagnosing prostate carcinoma, which reportedly lacks expression of high-molecular-weight cytokeratin. A recent report questioned the specificity of this marker, describing immunopositivity for high-molecular-weight cytokeratin in a small series of metastatic prostate cancer. We have also noted rare cases of prostate lesions on biopsy with typical histological features of adenocarcinoma showing immunopositivity for high molecular-weight cytokeratin, either in tumor cells or in patchy cells with the morphology of basal cells. In some of these cases, it was difficult to distinguish cancer from out-pouching of high-grade prostatic intraepithelial neoplasia. To investigate whether prostate cancer cells express high-molecular weight cytokeratin, we studied 100 cases of metastatic prostate carcinoma and 10 cases of prostate cancer invading the seminal vesicles from surgical specimens. Metastatic sites included regional lymph nodes (n = 67), bone (n = 19), and miscellaneous (n = 14). Cases with any positivity for high-molecular-weight cytokeratin antibody (34betaE12) were verified as being of prostatic origin with immunohistochemistry for prostate-specific antigen and prostate-specific acid phosphatase. Only four cases were detected positive for high-molecular-weight cytokeratin. In two cases (one metastasis, one seminal vesicle invasion) there was weakly diffuse positivity above background level. Two metastases in lymph nodes showed scattered strong staining of clusters of tumor cells, which represented <0.2% of tumor cells in the metastatic deposits. These positive cells did not have the morphology of basal cells. We conclude that prostate cancer, even high grade, only rarely expresses high-molecular-weight cytokeratin. This marker remains a very useful adjunct in the diagnosis of prostate cancer. PMID- 9989841 TI - Lymphocytic gastritis: association with etiology and topology. AB - Lymphocytic gastritis (LG) is an uncommon chronic gastritis characterized by lymphocytosis of foveolar and surface epithelium. Lymphocytic gastritis is associated with celiac disease, Helicobacter pylori (HP) gastritis, and varioliform gastritis, but its topology and severity with respect to the associated entities have not been studied in detail. Therefore, we studied 103 patients with LG classified according to the associated entities, including the distribution and severity of LG in the 70 patients from whom biopsy specimens of both antrum and body were available. In 84 patients (82%), a distinct associated entity was identified, including 39 with celiac disease, 30 with HP infection, 4 with varioliform gastritis, 2 each with inflammatory polyp, Crohn's disease, human immunodeficiency virus infection, lymphoma, and esophageal carcinoma, and 1 with lymphocytic gastroenterocolitis. Lymphocytic gastritis was found in 33% of patients with celiac disease and 4.1% of histopathologically defined HP gastritis. The severity of intraepithelial lymphocytosis was greater in antrum than in body in 83% (20 of 24) of LG associated with celiac disease, but in only 19% (4 of 21) of LG associated with HP infection (p < 0.00002). All four patients with varioliform gastritis had more severe involvement of body. Lymphocytic colitis was common (38%, 5 of 13) in celiac disease with LG. Our results indicate that lymphocytic gastritis most commonly occurs in celiac disease and HP infection, but rarely with other entities. The topology of LG can direct the clinical evaluation for associated disease. PMID- 9989843 TI - Florid cystic endosalpingiosis with tumor-like manifestations: a report of four cases including the first reported cases of transmural endosalpingiosis of the uterus. AB - Four cases of endosalpingiosis presenting as masses that resembled neoplasms are described in women 20, 41, 43, and 74 years of age. Each case was referred in consultation because of difficulties in pathologic diagnosis. In two patients, multiple cysts that involved the serosal surfaces of the uterus and adnexa in one case, and the colon, rectosigmoid, pelvic sidewalls, and the cul-de-sac in the other, were excised. In the other two cases, hysterectomy was performed for an enlarged cystic cervix in one case and presumed uterine leiomyomas in the other. In both of these cases, the uterine cervix and lower part of the uterine corpus were extensively involved by multiple cysts on gross examination, and in one of them, a frozen section of the cervical lesion was initially interpreted as "suspicious for invasive minimal deviation adenocarcinoma." On microscopic examination, benign endosalpingiotic glands and cysts were found in all four cases, with striking transmural involvement of the uterine cervix and lower uterine segment and contiguous corpus in the two cases with uterine involvement. The latter two cases are the first examples, to our knowledge, of endosalpingiosis involving the wall of the uterus; the differential diagnosis in these cases includes minimal deviation adenocarcinoma and florid tubal metaplasia with cystification. The four cases in this report, and rare previously reported cases, indicate that although usually a microscopic finding, endosalpingiosis can rarely present as a clinically or grossly evident mass that can be confused with a neoplasm. PMID- 9989842 TI - Adamantinoma-like Ewing's sarcoma: genomic confirmation, phenotypic drift. AB - Ewing's sarcoma, a highly malignant neoplasm, is characterized by an 11;22 translocation [t(11;22) (q24;q12)], resulting in the fusion of genes FLII and EWS. Adamantinoma of extragnathic bones, a low-grade malignant neoplasm with epithelial features, is not typically considered in the differential diagnosis of Ewing's sarcoma. In this study, three osseous Ewing's sarcomas with histological, immunohistochemical, or ultrastructural epithelial features were subjected to reverse transcription-polymerase chain reaction and sequencing studies for the Ewing's sarcoma molecular rearrangement. (Two of the three cases were originally described as adamantinomas or nontypical Ewing's sarcoma before the availability of genetic characterization.) In addition, traditional cytogenetic analysis and a unique combined interphase molecular cytogenetic/ immunocytochemical approach with bicolor 11;22 translocation breakpoint flanking probes (cosmids) and pancytokeratin antibodies were performed on one neoplasm. At(11;22) (q24;q12) was found in one neoplasm and a type II EWS/FLI-1 fusion transcript was detected in all three neoplasms. The combined genetic/immunocytochemical approach revealed the presence of the 11 ;22 translocation in the nuclei of cytokeratin immunoreactive cells. These genotypic and phenotypic findings delineate a novel Ewing's sarcoma histologic variant, "adamantinoma-like Ewing's sarcoma." PMID- 9989844 TI - Double immunolabeling with cytokeratin and smooth-muscle actin in confirming early invasive carcinoma of breast. AB - Histopathological identification of invasive breast carcinoma in its earliest phases is fraught with pitfalls. Preinvasive malignant lesions complicated by radial scar, sclerosing adenosis, and lobular cancerization, among other lesions, may simulate invasive carcinoma. Fibrosis, inflammatory reaction, and other stromal changes around in situ carcinoma may mask microinvasive foci on routine stains. Conventional immunohistochemistry to demonstrate basement membrane or myoepithelial cell layer may not, by itself, be unequivocally diagnostic of invasion. We performed a novel double immunoenzyme labeling technique using an avidin-biotin complex peroxidase-diaminobenzidine system for smooth-muscle actin followed by an alkaline phosphatase anti-alkaline phosphatase-new fuchsin system for cytokeratin antigen on formalin-fixed, paraffin-embedded histology sections to evaluate 32 such problematic cases. The initial histologic impression with hematoxylin and eosin staining alone was as follows-first group: microinvasive carcinoma-10; second group: carcinoma in situ--"stromal invasion cannot be ruled out"--15; third group: frankly infiltrating carcinoma of various grades and morphologic types-6. The last group served as positive control for invasion. One fibroadenoma with fine-needle-aspiration-induced artifact simulating stromal invasion was also included. The double immunoenzyme labeling technique imparted a dark brown color to the myoepithelial cells and a vivid red color to the epithelial cells, making individual or loosely cohesive groups of malignant epithelial cells infiltrating the stroma easily detectable, whereas their in situ counterparts were contained within dark brown myoepithelial boundaries. The TNM 1997 definition of pT1mic, i.e., extension of malignant cells in the stroma with no focus measuring >0.1 cm, was followed to classify microinvasion. In the first group, microinvasion was confirmed in six cases but was not demonstrable in four. In the second group, definite invasion was identified in five cases, ruled out in nine, and in one case the suspicion of early invasion could not be entirely ruled out even after double immunoenzyme labeling. Thus, it was possible to render a definite opinion regarding presence or absence of invasion in 24 of 25 (96%) cases diagnosed as or suspected to be microinvasive. The precise and simultaneous elucidation of topography between malignant cells and myoepithelial cells on a single permanent section makes this technique a useful diagnostic tool in the evaluation of those cases of breast carcinoma that exhibit equivocal invasion. PMID- 9989845 TI - The spleen in the Wiskott-Aldrich syndrome: histopathologic abnormalities of the white pulp correlate with the clinical phenotype of the disease. AB - The Wiskott-Aldrich syndrome (WAS) is a X-linked hematologic disorder characterized by thrombocytopenia, eczema, and immunodeficiency of variable severity. Reported here are the results of a morphologic, morphometric, and immunophenotypic analysis of splenic lymphoid tissue in 12 WAS patients with documented molecular defect and with different disease severity. Spleens from 29 age-matched patients with different diseases were used as controls. Paraffin embedded tissue (from all cases) and fresh-frozen samples (from 5 WAS patients and 4 control subjects) were used to study the different white pulp compartments by classic morphologic, immunophenotyping, and image analysis techniques. Data were statistically analyzed by both parametric and nonparametric tests. Spleens from WAS patients showed a significant depletion of the total white pulp (p = 0.0008), T cell (p < 0.05), and B cell (p = 0.0002) areas and marginal zone (MZ) thickness (p < 0.0001). Among WAS patients, a negative correlation was found between the score of severity of the disease and all variables considered (Spearman's rank correlation coefficient, r = -0.79, r = -0.73, r = -0.68, and r = -0.56, respectively). In conclusion, this study shows that in WAS a general depletion of the splenic white pulp occurs, supporting the evidence that WAS is characterized by a combined immune defect. The significant reduction of the MZ may explain the inability of WAS patients to mount a response to T-independent antigens. PMID- 9989846 TI - Subchondral acute inflammation in severe arthritis: a sterile osteomyelitis? AB - Although arthritis is often associated with synovial inflammation, the osseous changes in inflammatory and degenerative arthritis are principally reactive, and typically lack an acute inflammatory component. We have recently encountered several osteoarticular specimens removed at the time of large joint arthroplasty that have shown a distinctive pattern of subchondral acute inflammation (SCAI) resembling acute bacterial osteomyelitis. These microscopic findings heretofore have not been recognized as a component of the histopathology of arthritis. To determine the frequency of SCAI, we examined slides (mean four per case) from 164 hip arthroplasties performed at one of our institutions in a single year. A total of 10 cases of SCAI, including the 4 original examples (2 humeral head specimens, 2 femoral head specimens) and 6 identified from the slide review are described in this report. Eight patients were female and two were male (ages 54-86 years, mean 70, median 70). All had severe degenerative joint disease, six had rheumatoid arthritis, and three had osteonecrosis. In none was there a clinical or intraoperative suspicion of infection. Cultures of joint fluid or bone were not performed. In all cases, the inflammation was subchondral (within 1.0 cm of the joint surface), and it was frequently associated with subchondral cysts. In osteonecrotic foci, the suppurative inflammation was diffuse within the marrow space, whereas in viable bone it was nodular and vaguely granulomatous. Special stains for organisms were negative. None of the patients was treated with long term IV antibiotics. There has been no septic loosening of the prostheses at follow-up intervals ranging from 5 to 36 months (mean: 17 months). Our observations, to the best of our knowledge, are novel. Although we cannot definitively exclude bacterial infection as a cause of SCAI, the histologic and clinical features suggest that SCAI likely represents a noninfectious sterile form of inflammation. Subchondral acute inflammation is possibly secondary to synovial fluid insudation into subchondral cancellous bone in the setting of severe osteoarthritis and/or rheumatoid arthritis. PMID- 9989847 TI - Multiple familial gastrointestinal autonomic nerve tumors and small intestinal neuronal dysplasia. AB - Multiple small intestinal stromal tumors were removed from mother and natural daughter within 15 months of each other. Both had long histories of recurrent iron deficiency anemia and upper gastrointestinal bleeding. Light microscopy revealed that the tumors had arisen in conjunction with diffuse hyperplasia/ dysplasia of Auerbach's myenteric plexus. Immunohistochemistry generally did not show myogenic or paraganglionic phenotypes; CD34 was positive in most tumors. Electron microscopy confirmed the association with the abnormal Auerbach's plexus and showed the structure of gastrointestinal autonomic nerve tumors (GANTs). These findings provide information as to the origin and evolution of GANTs, and also have implications for the clinical management of these tumors which appear to occur more frequently than previously thought. PMID- 9989848 TI - Clinicopathological significance of poorly differentiated thyroid carcinoma. AB - The clinicopathological importance of a heterogeneous group of poorly differentiated thyroid carcinomas is not fully understood. Using data obtained from 303 surgically treated patients with differentiated thyroid carcinomas, the correlations between the aggressive histologic features and the clinicopathological findings, postoperative recurrences, and prognosis were retrospectively examined. In 201 cases, the carcinomas were well differentiated. The remaining 102 cases of poorly differentiated carcinomas were divided into two groups: focal-poorly differentiated (<10%) and diffuse-poorly differentiated (> or = 10%) carcinomas according to the extent of the poorly differentiated component. These poorly differentiated carcinomas were associated with high age (focal-poorly differentiated and diffuse-poorly differentiated versus well differentiated: 55 years and 59 versus 49; p < 0.0001), frequent presence of lymph node metastases (70% and 66% versus 48%; p = 0.0099) and distant metastases at diagnosis (11% and 11% versus 2%; p = 0.0098), and extrathyroidal invasion (53% and 53% versus 21%; p < 0.0001). There was independent correlation with age and the presence of extrathyroidal invasion. Cases of diffuse-poorly differentiated carcinomas showed frequent relapse (diffuse-poorly differentiated versus focal-poorly differentiated and well differentiated: 45% versus 30% and 24%; p = 0.0062) and poor prognoses (mean survival period = 9.15 versus 19.03 and 20.87 years; p < 0.0001) compared with the well and focal-poorly differentiated carcinomas. These data suggest that diffuse-poorly differentiated carcinoma is an important clinicopathological entity. PMID- 9989849 TI - Intraepidermal cytokeratin 7 expression is not restricted to Paget cells but is also seen in Toker cells and Merkel cells. AB - Histologically, extramammary Paget's disease and mammary Paget's disease (MPD) are characterized by large atypical cells distributed throughout the epidermis. Although classic examples of these disorders are easily diagnosed on morphologic grounds, some cases may cause differential diagnostic problems. Immunohistology with a wide variety of antibodies has been used as an aid for the identification of Paget cells, for their distinction from other entities, and for investigation of the origin or nature of the disorder. Recently, cytokeratin 7 has been proposed as a specific and 100% sensitive marker for Paget's disease. We studied 22 cases of mammary Paget's disease and 22 cases of extramammary Paget's disease with and without an underlying malignancy for their reactivity with monoclonal antibodies to cytokeratin 7 (CK7) and cytokeratin 20 (CK20). Our studies show that anti-CK7 is an effective but not 100% sensitive marker for Paget cells, staining 21 of 22 cases of mammary Paget's disease and 19 of 22 cases of extramammary Paget's disease, whereas CK20 stained 0 of 17 cases of mammary Paget's disease and 6 of 19 cases of extramammary Paget's disease. We also demonstrate that CK7, but not CK20, highlights intraepidermal clear cells with bland nuclear features (Toker cells) that have been reported in 11% of normal nipples. By using CK7 as a marker, however, we were able to identify Toker cells in most of the nipples we studied: 8 of 15 nipples from mastectomy patients without Paget's disease, and 15 of 18 autopsy cases (both male and female) with normal breasts and nipples. It also permitted us to perform more extensive phenotyping on them, showing that Toker cells share similar antigens with Paget cells and with cells lining the underlying normal lactiferous ducts. In 7 of 15 cases containing CK20-positive Merkel cells, CK7 was also seen to stain Merkel cells. In infrequent cases, Toker cells or Merkel cells may be so numerous focally that a CK7 stain may raise the possibility of involvement of the nipple by Paget's disease. An awareness of the CK7 reactivity of Toker cells and Merkel cells as well as attention to the cytologic features of the case should avoid this problem. PMID- 9989850 TI - Synovial sarcoma of the prostate with t(X;18)(p11.2;q11.2). AB - A case of monophasic synovial sarcoma of the prostate in a 37-year-old man is reported. Histologically, the tumor was chiefly composed of uniform spindle and oval cells, which often formed interlacing fascicles resembling those of fibrosarcoma. In some areas, the compact fascicles of tumor cells alternated with hypocellular myxoid tissue bearing a superficial resemblance to peripheral nerve sheath tumors, whereas small portions of the tumor showed a pericytomatous pattern consisting of polygonal cells arranged around dilated, thin-walled blood vessels. By immunohistochemistry, vimentin was detected in most cells, and a focal reactivity for epithelial membrane antigen was also observed. The tumor cells, however, were negative for keratin, S-100 protein, neuron-specific enolase, CD34, desmin, muscle-specific actin, and alpha-smooth muscle actin. Cytogenetic analysis and fluorescence in situ hybridization (FISH) using the cultured tumor cells demonstrated a translocation t(X;18)(p11.2;q11.2), an aberration specific for synovial sarcoma. To the authors' knowledge, this is the first report of a primary prostatic synovial sarcoma confirmed by cytogenetic analysis. PMID- 9989851 TI - Pyloric gland adenoma of the main pancreatic duct. AB - A case of a pyloric gland type adenoma of the main pancreatic duct in a 69-year old woman is reported. The tumor led to occlusion and cystic dilatation of the main duct in the pancreatic tail. The surgical resection specimen disclosed a polypoid, bilobed mass attached to the wall of the main pancreatic duct by a thin fibrous stalk. Light-microscopic examination revealed a well-demarcated nodule composed of closely packed tubular glands lined by columnar, mucin-secreting cells with abundant clear cytoplasm and basally oriented nuclei. Focal, mild cytologic atypia was seen. Pyloric metaplasia and focal papillary hyperplasia was present in the adjacent ductal epithelium. Periodic acid-Schiff reactions, with and without diastase predigestion, showed reactivity in the tubular glands, whereas alcian blue (pH 2.5) was negative. Immunohistochemical stains for chromogranin, serotonin, somatostatin, and gastrin failed to detect the respective antigens. Genetic analysis using polymerase chain reaction with mutant enrichment and allele specific oligonucleotide hybridization detected a single mutation at codon 12 of K-ras, which changed the wild-type glycine to arginine. This mutation is commonly found in invasive pancreatic ductal carcinomas. Although tumors with microscopic and immunohistochemical features consistent with pyloric gland adenoma have been described in the gallbladder, to our knowledge, this is the first reported case within the pancreatic ductal system. The finding of a K-ras, codon 12 mutation and the presence of focal dysplasia may denote neoplastic potential in association with this lesion. PMID- 9989852 TI - Ovarian prostatic tissue originating from hilar mesonephric rests. AB - Nonteratoid prostatic differentiation in the ovary of a parous, phenotypically normal, postmenopausal woman is reported for the first time, to the authors' best knowledge. The patient was a 70-year-old woman who underwent bilateral oophorectomy following pelvic ultrasound examination that showed enlargement of the left ovary and an equivocally abnormal Doppler signal. Histologic examination showed a normal right ovary and a left ovary enlarged by hilar cystic dilatation related to a proliferation of mesonephric remnants exhibiting various types of epithelial metaplasia, including hyperplastic rete and epididymal-like and clear cell epithelia resembling the lining of the seminal excretory system. These were closely associated, occasionally even merging, with a discrete area of prostatic acinar and smooth muscle differentiation in the cyst wall. The identity of the prostatic tissue was confirmed immunohistochemically by positive staining with prostate specific antigen and prostatic acid phosphatase. The lesion was associated with an incidental, microscopic hemangioma. A developmental malformative origin of this abnormality cannot satisfactorily be explained by current embryologic concepts. A hypothesis of a metaplastic induction of prostatic tissue by mesonephric remnants is proposed, since complex metaplastic changes coexisted within the cysts and even showed epithelial transitions with the prostatic acini. PMID- 9989853 TI - Happy Valentine's Day. PMID- 9989854 TI - Needle biopsies of prostate cancer. PMID- 9989855 TI - Sclerosing lung hemangioma. PMID- 9989856 TI - Sarcomas and related proliferative lesions of specialized prostatic stroma. PMID- 9989857 TI - Cutaneous involvement by neutrophil-rich, CD30-positive anaplastic large cell lymphoma mimicking deep pustules. PMID- 9989858 TI - Advance in the study of inhibin, activin and follistatin production in pregnant women. AB - This review summarizes the new information on the studies of inhibin, activin, and follistatin production in the placenta during human pregnancy. Inhibin and activin exert suppressive and stimulatory effects, respectively, on the release of FSH in the pituitary. Follistatin is bound to inhibin and activin and indirectly modulates the FSH release. The placenta produces these three proteins. The serum levels of inhibin, activin, and follistatin are elevated in pregnant women and decrease after delivery. The trophoblast cells from term placenta secrete inhibin and activin in the primary cultures. The production and mRNA expression of inhibin and activin are regulated by several stimulatory and suppressive hormones and growth factors in placental tissues. cAMP, Ca2+, and protein kinase-C may be involved in intracellular signal transduction in trophoblasts. Activin receptors are present on placental cells. Follistatin inhibits the binding of activin to ActRII receptor. Abnormal levels of inhibin and activin in maternal serum are observed in problem pregnancies and gestational diseases. Inhibin, activin, and follistatin may play roles in the regulation of reproductive endocrinology in pregnant women and the embryo/fetal development. PMID- 9989859 TI - Fetal growth and long-term consequences in animal models of growth retardation. AB - Perturbations of the maternal environment involve an abnormal intrauterine milieu for the developing fetus. The altered fuel supply (depends on substrate availability, placental transport of nutrients and uteroplacental blood flow) from mother to fetus induces alterations in the development of the fetal endocrine pancreas and adaptations of the fetal metabolism to the altered intrauterine environment, resulting in intrauterine growth retardation. The alterations induced by maternal diabetes or maternal malnutrition (protein calorie or protein deprivation) have consequences for the offspring, persisting into adulthood and into the next generation. PMID- 9989860 TI - Experience with fetoscopic cord ligation. AB - OBJECTIVE: In the case of a monochorionic multiple pregnancy with one non-viable fetus who compromises its co-twin, fetoscopic cord ligation may be performed. We describe our fetoscopic cord ligation technique and discuss the efficacy of cord ligation for salvaging the co-twin, based on available data. STUDY DESIGN: Descriptive case series of four cases and review of the cases published up to 1996. RESULTS: We performed four successful ligations. Of the 23 reported cases, which include the present series, two ligations failed. Four fetuses died in utero, and 17 were born alive at a mean of 8 weeks following the procedure. Two babies died in the perinatal period, a third after 60 days. Preterm uterine contractions do not seem to be a clinical problem. Preterm prelabour rupture of the membranes (PPROM) complicates about 40% of cases, the majority occurring prior to 32 weeks. CONCLUSION: Fetoscopic cord ligation is a feasible procedure with a 71% survival rate and a high risk for PPROM. PMID- 9989861 TI - Tracheoscopic endoluminal plugging using an inflatable device in the fetal lamb model. AB - OBJECTIVE: Intra-uterine tracheal occlusion has been proposed to reverse pulmonary hypoplasia, an important prognostic factor in congenital diaphragmatic hernia. We aimed to evaluate the feasibility and pulmonary effects of tracheoscopic tracheal obstruction with a detachable balloon. STUDY DESIGN: Fourteen mid-trimester fetuses out of 24 in 13 ewes underwent tracheoscopic balloon obstruction. Ten non-operated fetuses served as controls. Plugging was performed under fiber-tracheoscopy using a detachable balloon. Outcome measures consisted of: total operating time, tracheoscopy time, fetal survival, efficiency of plugging, and pulmonary effects. The Mann-Whitney test and linear regression were used for statistical analysis. RESULTS: Mean operating time and tracheoscopy time were 65+/-12 and 6.6+/-3.9 min, respectively. One intra-operative death occurred in each group. The post-operative mortality was 2/13 for cases and 2/9 for controls. In all 14 fetuses, the trachea was successfully obstructed. In the 11 treated animals born alive, the lung-to-body-weight ratio was 0.060+/-0.01, while in controls it was 0.031+/-0.01 (P = 0.0001). In a subset of six fetuses obstructed for 14-18 days, mean-terminal-bronchial density was 0.95+/-0.59, compared to 2.06+/-0.80 for controls (P = 0.046). CONCLUSIONS: Using fetal tracheoscopy, the trachea can successfully be obstructed with an inflatable balloon. Pulmonary hyperplasia is achieved when the obstruction lasts 2 weeks. PMID- 9989862 TI - Structural chromosome rearrangements in couples with recurrent fetal wastage. AB - OBJECTIVE: A review of the cytogenetic data in 1743 couples (3486 patients) with recurrent fetal wastage (RFW) who were examined for RFW at the Leuven Centre for Human Genetics in the period 1986-1995. These results were compared with a previous study in the period 1970-1985. SUBJECTS: Patients who had at least two first trimester miscarriages or patients who had a spontaneous first trimester abortion, preceded or followed by a second or third trimester fetal death. RESULTS: Chromosomal rearrangements were found in 5.34%. Two-thirds of these chromosomal rearrangements were autosomal balanced translocations. This finding is a 30-fold increase compared to the general population. Other chromosomal abnormalities included Robertsonian translocations, inversions and sex chromosomal abnormalities. DISCUSSION: The Leuven experience was compared with several other studies. Mechanisms causing these chromosomal abnormalities are presented. CONCLUSIONS: Chromosomal analyses are an important and necessary part of the etiological investigations in couples with RFW. PMID- 9989863 TI - Renin-like immunoreactivity in uterus and placenta from normotensive and hypertensive pregnancies. AB - OBJECTIVES: (1) To identify the distribution of renin-like immunoreactivity in placental bed, placenta-free uterine wall, placenta, fetal membranes, and intertwin membranes obtained from normal pregnancies and (2) to compare the findings in normal pregnancies with those in pregnancies complicated by various hypertensive disorders. STUDY DESIGN: Biopsies were taken from 31 normotensive pregnant women, eight of whom had twin pregnancies, and from 28 women with various hypertensive disorders of pregnancy. The anti-human renal renin monoclonal antibody, F37.1A1, was used for immunostaining. Histological structures were identified with standard H&E and PAS techniques, supplemented with immunostaining using the specific cell markers CD68 and cytokeratin. RESULTS: Renin-like immunoreactivity was found in cytokeratin immunolabelled placental syncytiotrophoblast, amnionic and glandular epithelium, but most consistently in CD68 immunolabelled maternal and fetal macrophages. The distribution of renin-like immunoreactivity throughout the pregnant uterus roughly parallelled reported renin concentrations in the various tissues, while its localization conforms also with that of cathepsin D. There were no obvious differences in renin-like immunolabelling between normotensive or hypertensive women. Renin-like immunoreactivity was particularly common in the atherotic lesions that are observed more often in pregnancies complicated with hypertensive disorders of pregnancy and/or intra-uterine growth restriction. CONCLUSIONS: The data complement earlier findings showing that only two of four anti-renal renin monoclonal antibodies, both of which cross-react with cathepsin D, give a positive immunostaining in placental tissue. They question whether classical concepts on renin localisation in uteroplacental tissues all relate to one and the same enzyme. The demonstration of renin-like enzymes in different cell types, including macrophages, may explain the diversity of functions that has been attributed to uterine renin. There were no differences between tissues obtained from normotensive and hypertensive pregnancies, except for the consistent presence of renin-like immunoreactivity in atherotic lesions. PMID- 9989864 TI - The origin and future of placental bed research. AB - Insights into the structural and functional relationships between maternal and fetal circulations in the human placenta require an understanding of trophoblast invasive behaviour in the uterine wall. The concept of physiologically changed spiral arteries, and the discovery of the restriction of this vascular adaptation in pre-eclamptic pregnancies, are two outstanding contributions of Professor Brosens to this field. His findings inspired different lines of research concerning regulatory mechanisms of trophoblast invasion, which eventually may have wider implications in the fields of cancerology, immunology and reproductive medicine. PMID- 9989865 TI - Microsurgery for intra-abdominal testicular retention. AB - OBJECTIVES: In cases of high intra-abdominal retention of the testis a standard technique of cryptorchidy treatment will not be able to bring down the testis into the scrotum. In this study we wanted to evaluate the feasibility and reliability of the technical aspects of testicular autotransplantations in children under the age of 5 years. STUDY DESIGN: A series of 25 microsurgical autotranslantations of testes performed on 17 boys since July 1984 are reviewed. Emphasis was placed on the microvascular transplantation technique, the age of the patient and the long term viability of the autotransplants. An end-to-end microvascular anastomosis between the deep inferior epigastric artery and the testicular artery was performed in an end-to-end way using mattress stitches to accommodate the difference in diameter between the donor and recipient vessels. Also the testicular veins were anastomosed to the deep inferior epigastric veins. RESULTS: Of the 25 transplantations (96%) were successful after a mean follow up of 24 months, the one failure was ascribed arterial thrombosis. CONCLUSION: Our results show a 96% survival of the transplanted testes using the end-to-end vascular anastomosis as described here. PMID- 9989866 TI - A decade of salpingoscopy. AB - With the introduction of the salpingoscopy of the tubal ampullary mucosa in the 1980s, this diagnostic endoscopic examination not only disclosed an exciting world of sharp and detailed in vivo images of the actual site of human fertilization. Its systematic use in the assessment of the tubal factor in subfertile couples also provides specific, clinically relevant and prognostically valuable information, since it clearly demonstrates the presence or absence of anatomical distortions, especially adhesions between and destruction of mucosal folds, on a micro-endoscopic, i.e., mucosal level. The routine salpingoscopy of a free, patent tube is easy to perform and the procedure then takes about 10 min for both sides. In contrast with hysterosalpingography, a proximal (e.g., tubocornual or isthmic) block does not prevent us from examining the ampullary mucosa with the salpingoscope, whereas a small incision at the site of the occlusion with one of the techniques of operative laparoscopy, enables the inspection of the mucosa of a hydrosalpinx. With salpingoscopy, and using a simple classification system, a trained endoscopist can evaluate the sequelae of tubal inflammatory disease and their impact on fertility nearly as efficiently as with mucosal microbiopsies and they can direct their patients accordingly, either towards reconstructive (micro)surgery or towards medically assisted reproduction. In case of a tubal pregnancy, the effort to salpingoscopically evaluate both the affected and unaffected side may help to understand the underlying ethiology of the ectopic. Since patency and a normal appearance of the fimbriated end surely do not imply the absence of endoluminal pathology, it is advisable to select only salpingoscopically normal tubes to perform tubal transfers of gametes, zygotes or embryos. In the still ongoing discussion regarding preventive salpingectomy prior to IVF-ET in case of a uni- or bilateral hydrosalpinx, blind victimization of the Fallopian tube can in our opinion be avoided by a proper endoscopic selection of cases. PMID- 9989867 TI - Intracytoplasmic sperm injection in the treatment of male subfertility. AB - OBJECTIVE: To evaluate the results obtained after intracytoplasmic sperm injection (ICSI) in couples with male factor subfertility. DESIGN: Retrospective analysis of results obtained after ICSI in the unit of in vitro fertilisation in a private centre for infertility. RESULTS: Application of ICSI in treatment cycles for male subfertility resulted in a fertilisation rate of 62%. An embryo transfer was done in 98% of the cycles, resulting in a 24% pregnancy rate/ET or 22% per cycle. CONCLUSION: ICSI is the first microfertilisation technique with reproducible high fertilisation rates in different centres and the method of choice in the treatment of severely impaired sperm quality. Although, up to now, no higher incidence of congenital malformations has been reported, except for sex chromosomal anomalies, careful genetic counselling is mandatory because of the risk of transmitting genetically defined male subfertility to the next generation. PMID- 9989868 TI - Gregorius-Josephus Jacquelart, born in 1759, the first andrologist at the University of Leuven. AB - At the time of his death in 1776, most medical doctors in Paris challenged the views of Theophile de Bordeu on the "hormonal" action of internal secretions. At the University of Leuven, however, his concepts on the hormonal activity of semen had been positively approached in 1780 on the occasion of a public debate (disputatio), conducted by the medical student, Gregorius-Josephus Jacquelart. Therefore, we consider G.J. Jacquelart as being the first andrologist at the University of Leuven. PMID- 9989869 TI - Genetic abnormalities and male infertility. A comprehensive review. AB - The development of assisted reproductive technologies, such as intracytoplasmic sperm injection (ICSI) substantially improved the outlook for patients with severe male fertility problems. However this implies that for the first time genetic defects associated with male in- or subfertility might be transmitted to offspring and result in genetic disease [de Kretser DM, The potential of intracytoplasmic sperm injection (ICSI) to transmit genetic defects causing male infertility. Reprod. Fertil. Dev. 1995;7:137-142]. The knowledge of male specific fertility genes on the Y chromosome increased enormously in the last decade. The SRY gene plays a critical role in gonadal differentiation. DAZ, SPGY and related genes on the Y chromosome are very important for spermatogenesis. Interstitial Y chromosomal microdeletions encompassing the AZFa, b or c region have become an additional class of genetic abnormalities causing male infertility. A review is given of the different genetic aspects of male infertility. PMID- 9989870 TI - How useful is Leuven personalism in the world of bioethics? The test case of artificial insemination. AB - Personalism in ethics denotes any system based upon the value of the person. Several versions of personalist morals have been developed over the past 50 years. Some have had particular interest in the field of medical ethics. Here the question is being studied about one such system, the so-called Leuven personalist morals and its usefulness in today's world of bioethics. In order to test the usefulness of this system the case of artificial insemination is examined both in the early 1970s in the context of the Leuven clinics and, subsequently, in the 1990s in a US policy document. The investigation reveals strengths and weaknesses of this personalism. Regarding AID it reveals unresolved oppositions. The conclusion seems to be that this personalism had, no doubt, a profound impact upon medical ethics within its own circle but, as regards the universal usefulness of the system, serious doubts remain. PMID- 9989871 TI - In vitro fertilisation: the ethics of illicitness? A personalist Catholic approach. AB - In line with Professor Brosens' work at the K.U. Leuven, the ethical integration of in vitro fertilisation (IVF) was made possible in the context of personalism, what we will present here in its anthropological and theological foundations. This presentation is necessary to make clear that personalism is always in the making of the clarification of its foundations. The three basic anthropological options are then applied to the ethical integration of IVF. They will lead to three concrete criteria for clinical practice: stable heterosexual infertile couple as indication; the respect for the human embryo and the qualitative social organization of infertility treatment. This position of Catholic personalists is in contradiction with the teaching of the Church, declaring that the IVF practice is in itself illicit. The third and fourth parts of this article are devoted to this statement. First, by debating the official magisterial position, and second, by referring to probably one of the most crucial issues for the ethical debate on IVF in the Church: the moral status of the embryo. PMID- 9989872 TI - Battey's operation: an exercise in surgical frustration. AB - Robert Battey (1828-1895) introduced bilateral oophorectomy for the treatment of non-ovarian conditions in 1872, coining the term "normal ovariotomy" for the operation. Normal ovariotomy - a contradictio in terminis - was practised widely for several decades. Alfred Hegar (1830-1914), among many other gynaecologists, extended the indications of Battey's operation to include the treatment of various ovarian conditions as well, e.g., small tumors. Better insight into female physiology and ovarian function finally pushed the sinister operation of Robert Battey from the scene. PMID- 9989873 TI - Steroid hormone-dependent myometrial zonal differentiation in the non-pregnant human uterus. PMID- 9989874 TI - "The Flemish Giant", reflections on the defense against endometriosis, inspired by Professor Emeritus Ivo A. Brosens. AB - Reproductive research benefits from combining animal and clinical studies. In Leuven, rabbits have constituted an animal model for many reproductive disorders, especially for those that involved surgical treatment. Much of what has been learned from animal experiments has been applied to human clinical reproductive research soon after. In this manuscript we wish to address the problem of the constant intra-abdominal battle between the menstrual aggressor and the peritoneal defense. From all published evidence we may conclude that endometriosis appears to be a dynamic disease, especially in the early phase, with subtle, atypical lesions emerging and vanishing again. In the end however the peritoneal defense system will prevail and the disease will be contained in the majority of patients. When doing repeat laparoscopies in young patients one should be prepared to encounter more advanced histological types of lesions, which not necessarily do have to indicate more advanced stages of the disease: the classical, blue and black powderburn spots and blueberry lesions reflect the extinguishing phase of the dynamic endometriotic process, and herald its inactivated histological end-stage. The dynamic phase of the disease may involve a varying interval of each patient's life, and medical suppression of the activity of the implants during this interval may lead one to conclude erroneously that treatment has been effective. If subsequently (after the end of medical suppression of the activity of the lesions) ovarian activity resumes and the lesions are stimulated again by ovarian steroids, their productive activity returns. Recurrence of disease may be diagnosed if at that stage a laparoscopy would be performed, whereas in reality only reactivation of temporarily obscured lesions did occur. The suppressed, dormant (but never absent) lesions produce mucus again, desquamation occurs, and reaction by the surrounding tissue. The inflammatory response, the local hyperemia and the neogenesis of vessels accentuate the presence of previously invisible endometriosis lesions and make them visible again. Endometriosis resumes its temporarily halted natural course of development, tissue remodeling occurs again, the battle between the aggressor and the defense resumes and waxing and waning of the several types of lesions, red, white and black, can be found again. PMID- 9989875 TI - Biases in the endometriosis literature. Illustrated by 20 years of endometriosis research in Leuven. AB - AIM: To review the Leuven data on endometriosis to demonstrate the shifts that occurred over the years in diagnosis of endometriosis, classification of women with endometriosis and thus in interpretation of results. RESULTS: The contributions to the LUF syndrome, to non-pigmented endometriosis, to cystic ovarian endometriosis, to deep endometriosis, to endometriosis as an immunologic disease and to the development of an animal model of endometriosis, illustrate the persistent interest in endometriosis over 20 years. Using these data it can be shown how progressively the recognition of endometriosis caused important shifts from women who in the beginning of this period were classified as normal, to women who later became classified as having minimal or mild endometriosis. This was caused initially by the active search for small typical lesions and later by the recognition of non-pigmented lesions as endometriosis. The second important shift was caused by the recognition that deep endometriosis is not only a frequent disease, but that these women are predominantly classified as having mild to moderate endometriosis and even as women without endometriosis. The third shift is still ongoing, since the deep lesions reported become progressively smaller, by the "enthusiasm" of the surgeons, and by the introduction of a menstrual clinical exam. A fourth bias in the literature concerns the diagnosis and treatment of cystic ovarian endometriosis. Together with these shifts in recognition and treatment of endometriosis, our understanding of the physiopathology of endometriosis has changed. This is illustrated by the new concepts which have emerged over this period. These are, the focal treatment of cystic ovarian endometriosis, the concept that mild endometriosis could be a normal physiological condition and the endometriotic disease theory. CONCLUSION: To interpret the data of the literature we should be aware of the shifts that have occurred in the classification of endometriosis over the past 20 years, and which still can hamper the comparison of results between research groups. PMID- 9989876 TI - Counselling of the climacteric woman. Diagnostic difficulties and therapeutic possibilities. AB - The psycho(patho)logical disorders during climacteric can only be adequately diagnosed and treated if the gynaecologist also pays clinical attention to the biographically related adaptation troubles of the woman in (peri)menopause. Psychoneurotic and psychosomatic reactions are frequent; psychotic reactions are rarely seen. The anxiety neuroses of this age of life are triggered less by sexual factors, but more by angry impulses. This anxiety can be expressed in a paranoid behaviour. Most adaptation difficulties and psychiatric disorders during menopause can and should be effectively treated by the gynaecologist. Theoretical understanding and practical experience concerning the counselling of psychosomatic patients are indispensable. PMID- 9989877 TI - Lymphocytes and dendritic cells in the normal uterine cervix. An immunohistochemical study. AB - OBJECTIVE: Assessment of the appearance, distribution and numerical density of immune cell populations in the normal human uterine cervix. STUDY DESIGN: SETTING: University Hospital Gasthuisberg. SUBJECTS: 29 healthy women undergoing total hysterectomy for non-cervical benign uterine disease. ANALYSIS: Immunohistochemistry and morphometrical analysis on histological sections containing ectocervix, transformation zone and endocervix, using antibodies against the following antigens: HLA-DR, CD4, CD22, CD1a and CD8. STATISTICAL ANALYSIS: Wilcoxon rank sum test. RESULTS: Lymphocytes in the epithelial and stromal compartments are predominantly T-lymphocytes. Intraepithelial T lymphocyte and Langerhans' cell densities and their distribution are not influenced by the menstrual cycle and are the same in both ectocervix and transformation zone. CONCLUSION: The wide variation of T lymphocyte subpopulations and Langerhans' cell densities in the normal epithelium of the uterine cervix is stressed. We are the first to present a large and well-defined control series, which is indispensable to study the effect of smoking and other factors on the cervical immune system. PMID- 9989878 TI - Some genetic aspects of ovarian tumors. PMID- 9989879 TI - Genetic basis of uterine leiomyoma: involvement of high mobility group protein genes. AB - Uterine leiomyoma is a common benign smooth muscle tumor occurring in 20 to 30% of women over 30 years of age. Cytogenetic analysis of such tumors has revealed that over 60% of them have a normal karyotype but also that they sometimes carry recurrent chromosome aberrations, e.g., aberrations involving the short arm of chromosome 6 or the long arm of chromosome 12. Precise mapping of chromosome breakpoints of such recurrent chromosome translocations and molecular characterization of DNA regions immediately flanking such breakpoints have proven to be a successful approach to identify and isolate genes involved in tumor development. Recently, application of such a research strategy on translocations in uterine leiomyoma involving either chromosome 12q13-15 or 6p21 has led to the discovery that two members of the high-mobility group (HMG) protein gene family, HMGIC and HMGIY, are frequently rearranged in such tumors. The developmentally regulated HMGIC and HMGIY genes encode closely related, low-molecular-mass proteins, which are assumed to function as architectural factors in the nuclear scaffold and to be critical in the assembly of stereospecific transcriptional complexes. The frequent rearrangement of the HMGIC and HMGIY genes in uterine leiomyomas suggests that these genes are directly involved in the aberrant growth control observed in these tumors. Studies of a number of other benign solid tumors - most of them in tissues of mesenchymal origin - indicated that involvement of HMGIC is not restricted to uterine leiomyomas, suggesting that benign solid tumor formation might have a common genetic denominator. The possible role of HMG genes in growth control is further supported by results from gene targeting experiments in mice, which indicate that HMGI-C plays an important role in mammalian growth and development, as inactivation of the murine HMGIC gene resulted in the pygmy phenotype. The discovery that high mobility group protein genes might be crucial factors in the formation of uterine leiomyoma provides a new opportunity for developing alternative therapeutic strategies. PMID- 9989880 TI - Transplantation with peripheral blood stem cells, manipulated or unmanipulated, for the treatment of high-risk childhood leukemia. AB - Collection of peripheral blood stem cells (PBSC) does not require anesthesia or multiple marrow aspirations, and hence, is far less invasive than bone marrow collection. Most importantly, PBSC can be collected from the body's entire pool of HSC to provide more stem cells than marrow aspiration performed at localized iliac bones. This leads to the faster recovery of hematopoiesis after PBSC transplantation (PBSCT) than after bone marrow transplantation and makes 'cell component therapy' far more effective with PBSC. This review will present our pediatric experience of transplants with PBSC, purified or unmanipulated. PMID- 9989881 TI - Collection of peripheral blood stem cells in pediatric patients: a concise review on technical aspects. AB - Peripheral blood stem cells (PBSC) are now routinely collected for use as hematopoietic support after high-dose chemotherapy for various malignancies. Nevertheless, few data are still available on PBSC collection in pediatric patients, owing to technical problems associated with the leukapheresis procedure in children. This paper briefly summarizes current knowledge about some technical aspects of pediatric leukapheresis for PBSC collection, according to the review of the literature and our personal experience on 60 procedures performed in 36 children affected with various malignancies. Technical issues include venous access, risk of volume shift due to exceeding extracorporeal circulation, and anticoagulation, that can induce severe side-effects. Moreover, criteria for optimizing the PBSC harvesting procedure in children, in particular the correct timing of leukapheresis, are discussed. PMID- 9989882 TI - Peripheral blood stem cell collection and transplantation in paediatric malignancies: a monocentric experience. AB - Thirty-seven patients underwent peripheral blood stem cell (PBSC) collection from May 1994 to May 1997. Twenty-five were males and 12 were females, the median age at collection was 11.5 years (range 1-27.4) and the median weight was 38 kg (range 9-80). As mobilising chemotherapy, cyclophosphamide, etoposide, doxorubicin and cytosine arabinoside were the drugs most frequently used in association with G-CSF for a total of 47 courses. Sixty-one aphereses were performed with a median collection of CD34+ and CFU-GM cells/kg of 3.6 x 10(6) (range 0.6-31.8) and 24.4 x 10(4) (range 0.1-1260), respectively. Minimal residual disease (MRD) was found in five of the 30 investigated aphereses. Twenty one of the 37 patients underwent high-dose chemotherapy with autologous stem cell rescue: in seven the stem cell source was peripheral blood and bone marrow. The median duration of hospitalization was 18 days for the PBSC group and 23 days for the PBSC/ABMT group. Overall survival was 78.7% at a median follow-up of 18 months (range 2-31) and the DFS was 52% without difference depending on stem cell source. Compared to a historical group of ABMT patients, the PBSC group showed a statistical advantage in terms of neutrophils and platelet engraftment, blood and platelet requirements, and length of hospitalization. PBSC collection is a feasible procedure also in the paediatric setting providing that vascular access is adequate. As already reported, PBSC transplant results in faster engraftment and shorter hospitalization that could allow a better utilization of health financial resources. The question whether the source of stem cells could influence transplant outcome would require a prospective randomised study. PMID- 9989883 TI - Cytofluorimetric analysis of CD34 cells. AB - The cytofluorimetric enumeration of CD34-positive cells is a useful method for measuring haematopoietic stem cells. The large variation of results between different laboratories, in multicenter quality control studies, could be due to multiple technical problems. CD34 analysis must be performed in whole blood and the NH4Cl or the NH4Cl-derived reagents give the best results in the lysis procedure. The monoclonal antibody for CD34 detection must be a class III, if possible PE-conjugated. Any differences were found in the absolute CD34 count using different analysis protocols: Milan, ISHAGE, Dutch, or a commercial kit, when the sample is fresh and in good viable condition. The multiparametric approach, using three or four colours simultaneously, could be required in scoring apheresis products from patients with CD34-positive blast cells (ie ALL of B cell origin) and in deciding the optimum time to start the leukapheresis, choosing, with an equal CD34 number, the moment at which the highest number of more immature progenitor cells (CD38-negative or dim, CD90-positive) is present. PMID- 9989884 TI - G-CSF-primed peripheral blood progenitor cells (PBPC) support in high-risk Ewing sarcoma of childhood. AB - Since 1993 pediatric patients affected by high-risk Ewing sarcoma for the presence at onset of a large pelvic mass and/or metastatic disease, were enrolled in a national pilot study comprehensive, finally, of a high-dose chemotherapy (HDCT) procedure with hemopoietic stem cell support. The HDCT procedure considered as consolidation of the disease status obtained after the first-line therapy was followed by the reinfusion of granulokine colony-stimulating factor primed (G-CSF) peripheral blood progenitor cell (PBPCT). Here we present the results in terms of treatment-related toxicity, hospitalization and rescue of the bone marrow function, in 17 pediatric patients enrolled in such a pilot protocol and submitted to HDCT and PBPCT at the end of first-line therapy. PMID- 9989885 TI - Current use and outcome of blood and marrow transplantation in childhood according to the Italian Registry. AB - Since 1985 data concerning patients affected by malignant and non-malignant diseases, aged <17 years, grafted in 16 centers nationwide, have been collected and stored in a central data base organized at the Associazione Italiana di Ematologia ed Oncologia Pediatrica (AIEOP) Operation Office within the AIEOP BMT Registry. The information, collected and structurally integrated with other specific disease-oriented national data bases, permitted the elaboration and the following publication of several analyses on survival, relapse probability and transplant-related mortality for the different diseases. PMID- 9989886 TI - Mismatched T cell-depleted hematopoietic stem cell transplantation for children with high-risk acute leukemia. AB - The aim of this study was to extend allogeneic hematopoietic stem cell transplantation to leukemia patients without a matched donor. To prevent graft failure, large doses of T cell-depleted hematopoietic stem cells were transplanted following a highly myeloablative and immunosuppressive conditioning regimen. Fifteen children with high-risk acute leukemia received T cell-depleted hematopoietic stem cells from full-haplotype mismatched family members after a conditioning regimen that included single-dose TBI, thiotepa, ATG and fludarabine. To prevent GVHD, marrow cells were T-depleted by soybean agglutinin and E-rosetting, peripheral blood cells by E-rosetting followed by positive selection of the CD34+ cells. No post-transplant prophylaxis for GVHD was administered. In all patients full donor-type engraftment was achieved. None of the evaluable patients developed either acute or chronic GVHD. Regimen-related toxicity was minimal. Five patients are alive and event-free at a median follow up of 18 months (range 13-28). All surviving patients have a good quality of life. Seven patients have relapsed. This study shows that GVHD and graft failure, which limited the use of full-haplotype mismatched bone marrow transplants, have been overcome. Since almost all children have a mismatched relative, advances in this area should make mismatched transplants a routine consideration for patients with high-risk leukemia without a matched related or unrelated donor. PMID- 9989887 TI - Allogeneic transplantation of peripheral blood progenitor cells in children: experience of two pediatric centers. AB - Between February 1995 and August 1997, 11 children (eight males, three females) aged 4-16 years (median 7 years) underwent allogeneic PBPC transplantation for treatment of hematological disorders. Seven patients with acute leukemia (n = 5 ALL, n = 1 AML) or lymphoma (n = 1) received primary allogeneic PBPC transplantation, four patients received a second allotransplantation for graft failure (n = 1 AML, n = 1 sickle cell anemia) or disease recurrence (n = 1 ALL, n = 1 MDS). Five donors were HLA-identical siblings, five were 0-1 antigen mismatched family members and one was a matched unrelated donor. Donors received G-CSF 10-12 microg/kg/day for 3-7 days, and underwent one or two leukaphereses. The median cell yield per donor expressed per kg of recipient body weight was as follows: mononucleated cells 10.8 x 10(8)/kg (range 4.7-21.2); CD34+ cells 8.6 x 10(6)/kg (range 3.2-22); CD3+ cells 3.7 x 10(8)/kg (range 2.7-7.5). All patients achieved an ANC >0.5 x 10(9)/l after a median of 12 days (11-18). An unsupported platelet count >50 x 10(9)/l was reached 15 days (13-21) after PBPC transplantation; four patients failed to reach this threshold. Acute GVHD (aGVHD) grades II to IV occurred in eight (73%) patients: seven of them experienced grade III-IV aGVHD. Seven patients evaluable for chronic GVHD (cGVHD) were scored as absent in five, limited in one and extensive in one patient. As of September 1997, six patients (55 %) were alive between 60 and 938 days post-transplant (median follow-up 274 days); four patients with malignancy were alive in CR after primary allotransplantation, two patients were alive after a second PBPC transplant. Five patients have died with the main causes of death being aGVHD (n = 3), ARDS (n = 1), relapse of the underlying disease (n = 1). In conclusion, despite the limited number of patients, these preliminary results indicate that PBPC may be considered as an alternative to bone marrow for allografting also in children. PMID- 9989888 TI - Feasibility of high-dose chemotherapy and autologous peripheral blood stem cell transplantation in children with high grade osteosarcoma. AB - An Italian-Scandinavian treatment and research protocol with high-dose chemotherapy and double peripheral blood stem cell (PBSC) transplantation has been designed in an attempt to improve overall results of children with metastatic osteosarcoma (OST). Six patients, aged 12-17 years, underwent PBSC mobilization with CY 4 g/m2 and VP-16 600 mg/m2 followed by G-CSF (n = 4 with recurrent disease) or ifosfamide 15 g/m2 plus G-CSF (n = 2 with synchronous metastases). The target dose of CD34+ cells for two transplant procedures was 8 x 10(6)/kg or more; conditioning regimen for both the grafts consisted of carboplatin 375 mg/m2/day for 4 days and VP16 450 mg/m2/day for 4 days. The first transplant was planned 2-4 weeks after the mobilization, the second transplant 4 6 weeks after the first graft. In three patients a single course of CY-VP16 mobilised a total number of CD34+ sufficient for two transplants; in the patient who did not obtain the target dose of CD34+ cells a bone marrow harvest was added. In the two other children high-dose ifosfamide failed to achieve the required CD34+ number: one patient underwent a single transplant procedure, one patient was successfully mobilized with doxorubicin 90 mg/m2 plus G-CSF. Patients underwent a median of two collections (range 2-4). Leukapheresis resulted in the collection of a median of 8.9 CD34+ cells/kg (range 1.3-14.8). The median time to granulocyte count recovery to more than 0.5 x 10(9)/l was 10 days (range 9-14 days) after the first graft and 11 days (range 10-12 days) after the second graft, respectively. Platelets recovered to 50 x 10(9)/l at a median of 11 (range 10-30 days) and 13 days (range 10-28) respectively after the first and the second graft. Conditioning regimen was well tolerated in all patients with mild extra haematological toxicity, also following the second transplant. Two patients grafted with metastases at diagnosis are alive and disease free 3 and 7 months from the transplant. One of the four patients transplanted for recurrent disease developed pulmonary metastases 2 months after the procedure; one patient is alive with significant reduction of tumor mass 1 month after the first transplant, one patient is alive without evidence of disease 9 months from the second transplant and one after a complete metastasectomy (tumor necrosis >90%) which followed the second transplant. With the limits of the small number of cases and the short follow-up, these preliminary results show that this approach may be promising for the treatment of patients with metastatic OST who currently are not cured by conventional-dose regimens. PMID- 9989889 TI - Peripheral blood stem cell collection from G-CSF-stimulated unrelated donors for second transplant. AB - Peripheral blood stem cells (PBSCs) collected following stimulation with cytokines are commonly used for autologous haematopoietic transplants. Currently, PBSCs are being used for syngeneic or allogeneic transplants from matched or haploidentical donors. However, many issues are still unanswered regarding the early or late side-effects cytokines have on recipients and on healthy donors. The aims of this paper were to evaluate the experience acquired worldwide in this field, to define the acceptability of stem cell donation by G-CSF-stimulated apheresis from unrelated donors after the failure of a first donation, and to assess side-effects of G-CSF on unrelated donors. The use of PBSCs has increased tremendously over the last few years and in the near future PBSCs will probably become the most relevant source of stem cells. Studies conducted so far have definitely concluded that G-CSF is safe and well tolerated. Results observed in transplants utilizing marrow stem cells compared with results obtained in transplants utilizing PBSCs have shown that patients undergoing this latter procedure recover earlier, require a lower number of transfusions and spend fewer days in hospital with a consequent decrease in costs. We concluded that a second transplant by G-CSF-stimulated apheresis from an unrelated donor is definitely acceptable and we designed a prospective study to better define all controversial aspects. Donors will be given 10 microg/kg/day of G-CSF subcutaneously for 5 days. One or two PBSC collection procedures will be performed: the first on day 5 and the second, if necessary, on day 6. Donors will be surveyed and blood counts monitored in a standardized manner during the process. PMID- 9989890 TI - Biological characterization of CD34+ cells mobilized into peripheral blood. AB - We review here the functional and kinetic characteristics of highly purified hematopoietic CD34+ mobilized into peripheral blood (PB) by granulocyte colony stimulating factor (G-CSF) with or without chemotherapy for autologous or allogeneic transplantation. Circulating CD34+ cells were evaluated for their colony-forming capacity and trilineage proliferative response to selected recombinant human (rh) CSF in vitro, and the content of very primitive long-term culture initiating cells (LTC-IC). In addition, the cycling status of PB CD34+ cells, including committed clonogenic progenitor cells and the more immature LTC IC, was determined by the cytosine arabinoside (Ara-C) suicide test and the acridine orange (AO) flow cytometric technique. By comparison, bone marrow (BM) CD34+ cells from the same individuals were studied under steady-state conditions and during G-CSF administration. Clonogenic assays in methylcellulose showed the same frequency of colony-forming unit cells (CFU-C) when PB primed-CD34+ cells and BM cells were stimulated with phytohemagglutinin-lymphocyte-conditioned medium (PHA-LCM). However, mobilized CD34+ cells were significantly more responsive than their steady-state BM counterparts to interleukin-3 (IL-3) and stem cell factor (SCF) combined with G-CSF or IL-3 in the presence of erythropoietin (Epo). Conversely, circulating and BM megakaryocyte precursors (CFU-MK) showed the same clonogenic efficiency in response to IL-3, GM-CSF and IL 3, IL-6 and Epo. Interestingly, very few CD34+ cells expressed the Mpl receptor and this finding resulted in the lower proliferative response of mobilized CFU-MK to the Mpl-ligand (megakaryocyte growth and development factor; MGDF), as compared to BM cells. After 5 weeks of liquid culture supported by the engineered murine stromal cell line M2-10B4 to produce G-CSF and IL-3, we reported a similar frequency of LTC-IC in PB and steady-state BM. Kinetic studies on PB and BM CD34+ cells, including LTC-IC, showed the low number of circulating progenitor cells in S and G2M phase whereas simultaneous DNA/RNA analysis and the Ara-C suicide assay demonstrated that the majority of PB CD34+ cells and LTC-IC are not quiescent (ie in G0 phase) being in G1 phase. Moreover, G-CSF administration prevented apoptosis in a small but significant proportion of mobilized CD34+ cells. Thus, our results indicate that mobilized and BM CD34+ cells can be considered equivalent for the frequency of both committed and more immature hematopoietic progenitor cells, although they show different kinetic and functional profiles. A further set of experiments indicated that G-CSF treatment did not alter the alloantigen presenting function of CD34+ cells which was mainly mediated by the upregulation of costimulatory molecules upon coincubation with allogeneic T cells. Taken together, these findings should allow a better understanding of PBSC transplantation. PMID- 9989891 TI - Transplantation of peripheral blood stem cells mobilized by haematopoietic growth factors in childhood. AB - Peripheral blood stem cells (PBSC), mobilised by means of haematopoietic growth factors (HGF) with or without chemotherapy, are being used routinely for autologous rescue after high-dose chemo-radiotherapy in paediatric patients with lymphoma and selected solid tumours because of the ease of collection and the accelerated kinetics of neutrophil and platelet engraftment as compared with bone marrow cells. Recent reports indicated that HGF-mobilised PBSC can also be employed in childhood as an alternative to bone marrow allograft when the donor is an adult or with the aim of reversing graft failure in patients who were previously given a marrow allograft. Notwithstanding this wide use of PBSC, several biological and clinical questions of crucial relevance are still unsolved. In this article, we will analyse: (1) the optimal timing for PBSC collection after cytokine-based mobilising regimens; (2) the variables affecting the yield of peripheral blood progenitors; (3) the minimum threshold and the optimal number of PBSC that should be infused for autologous and allogeneic transplant, respectively; (4) the biological mechanisms underlying mobilisation of haematopoietic stem cells into circulation; (5) the incidence of graft-versus host disease and the biological characteristics of donor lymphocytes in patients given allogeneic transplant of PBSC; and (6) the most relevant peculiarities in the kinetics of immune recovery of patients given allogeneic transplant of PBSC, as compared to bone marrow transplant recipients. PMID- 9989892 TI - Nutritional interventions for the prevention of maternal morbidity. AB - OBJECTIVE: To review the effectiveness of nutritional interventions to prevent maternal morbidity. METHODS: This is an overview of systematic reviews and individual randomized controlled trials (if no systematic review available) of nutritional interventions during pregnancy. For each nutrient intervention the main maternal morbidity data reported were extracted. These were pre eclampsia/eclampsia, pregnancy-induced hypertension, hemorrhage, anemia, infection and obstructed labor. In addition, the trial settings, the number of trials and participants' characteristics were systematically extracted. RESULTS: The systematic reviews considered in this paper had only few trials that reported the selected maternal outcomes. Outcome measures are based sometimes on one trial only. Most of the interventions compared single micronutrient supplementation with placebo/no treatment and did not show significant benefits for the supplementation groups. Calcium supplementation in women at high risk of pregnancy hypertension reduced the incidence of high blood pressure (RR, 0.35; 95% CI, 0.21-0.57) and pre-eclampsia (RR, 0.22; 95% CI, 0.11-0.43). Similarly, in women with low dietary calcium intake, calcium supplementation resulted in a significant reduction in the incidence of high blood pressure (RR, 0.49; 95% CI, 0.38-0.62) and pre-eclampsia (RR, 0.32; CI, 0.21-0.49). In women at low risk of pregnancy hypertension or with adequate baseline calcium intake, the beneficial effects of calcium supplementation are small and unlikely to be of clinical significance. Both, iron and folate supplementation reduced the number of women with low pre-delivery hemoglobin. CONCLUSIONS: Routine calcium supplementation seems to be a promising intervention for pregnant women at risk of developing preeclampsia or have low calcium intake, but these findings need to be confirmed with a trial with adequate power in different settings. In populations with high incidence of nutritional anemia routine iron and folate supplementation should be recommended during ante-natal care. It is unclear at this stage if adding vitamin A to iron and folate supplementation in anemia prevalent areas provides further benefits. There is inadequate data on the benefits or harms of routine iron or folate supplementation in adequately nourished populations. With regard to other micronutrient supplementation, such as zinc, magnesium and fish oil, randomized controlled trials with sufficient power to detect clinically important differences in maternal and infant outcomes are needed. PMID- 9989893 TI - Maternal syphilis and vertical perinatal transmission of human immunodeficiency virus type-1 infection. AB - OBJECTIVES: To identify risk factors for vertical HIV transmission that may provide opportunities for the prevention of future pediatric HIV infection. STUDY DESIGN: A prospective cohort of 44 pregnant HIV(+) women and their 53 offspring was followed between July 1989 and July 1996. RESULTS: Secondary and latent maternal syphilis infection was diagnosed in four pregnancies with VDRL titers > or = 1:128. Concurrent maternal syphilis infection was associated with 100% vertical HIV transmission (4/4), compared to 21% (3/14) deliveries that occurred in 13 women with only a history of treated sypillis (P = 0.01) and 14% (5/35) deliveries in women with no history of syphilis (P = 0.0015). Among non Zidovudine exposed pregnancies, 100% (3/3) patients with concurrent syphilis transmitted HIV to their infants vs. 0% (0/8) patients with only a history of syphilis (P = 0.006). A history of treated syphilis did not increase subsequent transmission risk compared to women with no history of syphilis (3/14 vs. 5/35, P = 0.41). One patient delivered twice during the study and received Zidovudine prophylaxis during both pregnancies. Her first pregnancy VDRL titer was > or = 1:128, during which she delivered an HIV infected child. Following successful treatment for syphilis (VDRL titer, 1:1), she conceived again and delivered an uninfected infant 11 months later. Additional risk factors significantly associated with vertical HIV transmission were prematurity and low birth weight. Variables studied but not statistically-related to HIV transmission included: other sexually transmitted diseases, maternal age, race, intravenous drug or cocaine use, prenatal care, route of delivery, duration of HIV(+) status, and CD4 count. CONCLUSION: Among HIV(+) women, concurrent syphilis infection, but not a history of syphilis, is significantly associated with vertical perinatal HIV transmission. Frequent screening and prompt treatment of syphilis in non-pregnant HIV(+) women may help prevent subsequent HIV infected pregnancies. PMID- 9989894 TI - Lumbar bone mineral density changes during pregnancy and lactation. AB - OBJECTIVE: To elucidate the change of bone metabolism in the lumbar trabecular and its relationship with serum hormonal changes in pregnancy and lactation. STUDY DESIGN: In a cross-sectional study, we measured the bone mineral density (BMD) of 2-4 lumbar vertebrae of 571 puerperae at days 3-5 postpartum and 341 healthy, non-pregnant women (control subjects) of approximately the same age by dual energy X-ray absorptiometry. In a longitudinal study, we also measured the BMD of 111 puerperae at 3 and 6 months after delivery. RESULTS: The mean BMD at days 3-5 postpartum was significantly lower than that of the control (1.013+/ 0.005 vs. 1.032+/-0.006 g/cm2, P = 0.019). The lactating group showed BMD decrement to 95.1+/-0.5% (n = 69) and 94.1+/-0.7% (n = 61) at 3 and 6 months postpartum, respectively, compared with days 3-5 postpartum, and the amenorrhea group showed the same tendency. The non-lactating group and resumption of menses group did not show a BMD decrement postpartum. In the lactating group, serum estradiol was significantly lower than in the non-lactating group at 3 months postpartum, serum prolactin and bone alkaline phosphatase levels were higher than in the non-lactating group at 3 and 6 months postpartum. CONCLUSIONS: Pregnancy may cause a decrease of lumbar BMD, and the lactation and amenorrhea also cause a decrease of BMD. In addition to lactation status, the ovarian dysfunction is one of the factors in bone loss during lactation. PMID- 9989895 TI - Selective tracheal suctioning to prevent meconium aspiration syndrome. AB - OBJECTIVE: To analyze the incidence and outcome of meconium aspiration syndrome (MAS) at Al-Yamamah Hospital, Riyadh, Saudi Arabia, where meconium-stained babies have intrapartum obstetrical cleansing of the upper airways, following which depressed/asphyxiated babies are intubated and vigorous babies are observed for 24 h. METHOD: The total live births, records of meconium-stained neonates who had intubations and of those observed, during a 6-year period were reviewed. RESULTS: During this period, there were 85562 live births. One in 325 births (0.27%) was complicated by MAS and the mortality rate was 7%. These figures concur with the reported incidence and mortality of MAS following routine combined obstetric pediatric suction of airways at birth. Of the 265 cases of MAS that occurred during this period, 237 were in the intubated group and 28 in the observed group. The babies of the former group had severe disease compared with that of the latter. All mortality was from the intubated group. CONCLUSION: Adequate obstetrical cleansing of the upper airway in vigorous babies may obviate the need for endotracheal intubation; intubation of depressed babies following this treatment may be useful. PMID- 9989896 TI - Detection of human papillomavirus types in cervical adenocarcinoma by the polymerase chain reaction. AB - OBJECTIVE: To determine the human papillomavirus (HPV) types in cervical adenocarcinoma of patients from Taiwan. METHODS: DNA was extracted from fixed tissues and polymerase chain reaction was performed in conjunction with a unique probe, pRSA I, allowing simultaneous detection of HPV types 6, 11, 16, 18, 31 and 33 from amplified HPV DNAs after endonuclease, RsaI, digestion. RESULTS: Of 69 tissues examined, 31.9% (22/69) were found to contain HPV DNA. Among 22 HPV positive specimens, no HPV types 6, 11, 31 and 33 were detected. On the other hand, HPV 16 and HPV 18 were found in 11 (15.9%) and 10 (14.5%) of HPV-positive specimens, respectively. One specimen (1.5%) was found to contain both HPV 16 and 18 DNAs. CONCLUSIONS: Our findings support that HPV 18, along with HPV 16, may play a certain role in the adenocarcinoma pathogenesis of the uterine cervix. PMID- 9989897 TI - Ultrasound or ultrasound and hormonal determinations for in vitro fertilization monitoring. AB - OBJECTIVE: To compare pregnancy rate, cost effectiveness, patients effort, related stress, and the ovarian hyperstimulation syndrome (OHSS) rate, between patients monitored for ovarian hyperstimulation using a combination of ultrasound and hormonal determination (combination protocol), in contrast to applying ultrasound only, in in vitro fertilization and embryo transfer (IVF ET). METHOD: This study was carried out on a total of 206 patients who underwent ovarian hyperstimulation with human menopausal gonadotropin and human chorionic gonadotropin (hMG/hCG) protocol. The first 110 patients were monitored every other day by ultrasound only protocol (Group I) while the next 96 patients were monitored daily by a combination protocol (Group II). The pregnancy rate, taking home baby rate, OHSS rate and total cost of monitoring for each patient in both groups were calculated and compared. The patients and the IVF team effort and stress were also compared. RESULT: Analysis of this study showed no statistical significant differences in clinical pregnancy rate and taking home baby rate between patients in protocol I and II (23.4% vs. 22.9%) and (14.8% vs. 14.3%), respectively. OHSS developed in only two patients--one in each group. The average cost of monitoring was significantly cheaper in Group I--78 Jordanian dinars (JD) vs. 222 JD in Group II (P < 0.0001). (NB: 1 USD = 0.7 JD). CONCLUSION: Ultrasound monitoring only proved to be cheaper, more convenient and less time consuming for both the patients and the IVF team. However, no significant difference was found regarding the clinical pregnancy rate and taking home baby rate between the two protocols. PMID- 9989898 TI - Abdominal hysterectomy practice patterns in the United States. AB - OBJECTIVE: To describe nationwide practice trends for two principal techniques of abdominal hysterectomy in the United States, numbers and rates of total (TAH) and supracervical (SCH) hysterectomy were reviewed with charges for each operation. METHODS: Practice patterns for all inpatient TAH and SCH discharges in the US from 1991 to 1994 were studied using HCUP-3 NIS, a nationwide hospital discharge database. Hysterectomies performed for malignant disease, vaginally or with laparoscopic assistance were not sampled. For each year studied, the number and rate of TAH and SCH, average length of stay (LOS), and mean institutional charge were evaluated. RESULTS: From 1991 to 1994, the US TAH rate (cases/10000 females) decreased significantly from 25.7 to 20.5 (P = 0.02). During the same interval the SCH rate increased significantly from 0.16 to 0.41 (P = 0.04). Nevertheless, TAH accounted for > 99% of all abdominal hysterectomies for each of the 4 years evaluated. The mean institutional charges for the two operations generally depicted SCH to be more costly than TAH. CONCLUSION: The national rates of TAH and SCH rates changed significantly in the United States from 1991 to 1994, with TAH declining and SCH increasing. This mix of cases continues to reflect a strong preference for TAH. Although hospital charges for both procedures increased during this study, these data show that SCH is more expensive than TAH. The much lower utilization of SCH renders nominal its impact on national healthcare expenditures, however. Further studies are needed to assess specific causative factors for these changes in US hysterectomy technique. PMID- 9989899 TI - A 4-year clinical analysis of ruptured uterus. PMID- 9989900 TI - The relationship between parity and labor pain. PMID- 9989901 TI - Maternal mortality in Fiji. PMID- 9989902 TI - Transvaginal ultrasound-guided electrocautery of the ovaries in infertile patients with polycystic ovarian disease. PMID- 9989903 TI - ACOG educational bulletin. Confidentiality in adolescent health care. Number 249, August 1998. American College of Obstetricians and Gynecologists. PMID- 9989904 TI - ACOG educational bulletin. Ovarian cancer. Number 250, August 1998 (replaces No. 141, May 1990). American College of Obstetricians and Gynecologists. PMID- 9989905 TI - ACOG committee opinion. Tubal ligation with cesarean delivery. Number 205, August 1998. Committee on Coding and Nomenclature. American College of Obstetricians and Gynecologists. PMID- 9989906 TI - ACOG committee opinion. New Pap test screening techniques. Number 206, August 1998. Committee on Gynecologic Practice. American College of Obstetricians and Gynecologists. PMID- 9989907 TI - Assessing eating patterns-an emerging research topic in nutritional sciences: introduction to the symposium. AB - In order to stimulate food habit research in nutritional sciences, in 1994 the International Union of Nutritional Sciences (IUNS) established Committee II/2 on Nutrition and Food Habits, which has the charge "to review the impact of changing food choice and habits on nutritional status". Within this broad task, priority has been given to methodological aspects of studies on the spatio-temporal structure of food and drink intake. Some principles of the study of eating patterns and the status of this research topic nutrition are described as an introduction to selected papers of a workshop on "Methodology to Identify and to Assess Eating Patterns" organized by the IUNS committee and held during the 16th International Congress of Nutrition in Montreal (Canada) on 28 July 1997. PMID- 9989908 TI - Dietary patterns and trends in the United States: the UNC-CH approach. AB - Over the past 2 decades our group of nutrition and economics researchers at the University of North Carolina at Chapel Hill has used a wide array of methods to study eating patterns and dietary trends. Our focus has been on characterising the way diet has changed over time and identifying some of the major factors underlying these trends. The complexity of this undertaking has led us to develop a number of unique systems for classifying foods and assessing the overall quality of diet. We have also addressed the challenges that exist when measuring changes in both the food supply and food-related behaviors over time. This paper summarises some of the methodological work related to food grouping, overall diet quality indices, and trends research as well as the challenges we still face in this arena. PMID- 9989909 TI - Meal patterns in the SENECA study of nutrition and the elderly in Europe: assessment method and preliminary results on the role of the midday meal. AB - The paper discusses the assessment method for meal patterns in the course of the SENECA follow-up survey in 1993 in eight study towns across Europe and relates the percentage of energy intake at the midday meal to geographical latitude, total energy intake, energy intake as snacks, number of cooked meals, time spent at the main meal and intake of milk products, fat and leafy vegetables. A questionnaire for the assessment of meal patterns in western Europe has to include the possibility to assess more than three meals per day as well as a variety of meals at any time of the day. Meal structures vary between cooked meals, bread- or soup-based meals, but may also consist of spoon food, salads or fruit. Positive correlations were found between the percentage of energy intake at the midday meal and the number of cooked meals consumed per day, negative relations were found between the percentage of energy intake at the midday meal and the geographical latitude as well as total energy intake, energy intake in form of snacks and consumption of milk products. PMID- 9989910 TI - The significance of eating patterns: an elderly Greek case study. AB - Eating patterns are a relatively neglected area of nutrition assessment with considerable potential health importance. Cross-cultural and socio anthropological studies provide insight into the great range of food patterns which are related to health, biochemical measurements and anthropometry. The International Union of Nutritional Sciences (IUNS) study of aged folk in food culturally disparate communities has provided opportunities to explore these issues. This paper uses cross-sectional data from the Greek arms of the IUNS study to explore associations between eating pattern variables (number of meals, time of meals, main meal for lunch and/or dinner, meal plus alcohol) and with the prevalence of self-reported heart disease and diabetes, body fatness, blood lipids, blood glucose and the overall variety of foods consumed. The eating pattern variables were not associated with blood lipids, self-reported heart disease or diabetes. Body fatness was negatively associated with the consumption of a greater number of meals/snacks daily (p<0.01), with the consumption of two cooked meals daily (p<0. 05) or when the main meal was consumed at lunch time (p<0.05) and when breakfast was consumed earlier rather than later in the morning (p<0.01). Later dinner times were positively correlated with a higher fasting blood glucose in non-diabetic elderly Greeks (p<0. 0005). A more varied diet was positively associated with the consumption of alcohol with dinner (p<0.0001) and with a greater number of meals/snacks daily (p<0.0001). These findings suggest that adherence to the traditional Greek eating pattern may be protective against obesity and appears to promote greater food variety. PMID- 9989911 TI - Meal patterns in middle-aged men in Southern Germany: results from the MONICA Augsburg dietary survey 1984/85. AB - Seven-day food records of the MONICA project Augsburg dietary survey, which were collected in 1984/85 from 899 men aged 45-64 years (random sample), were used to analyse meal patterns. The combination of the three traditional meals (breakfast, lunch, dinner) with one eating event between was most frequent, followed by two meals with two eating events between and three main meals without any other eating event (31.4 vs. 31.0 vs. 15.6% of all reported days). Breakfast delivered 17, lunch 29 and dinner 33% of the total daily energy intake; all other eating events delivered 21%. The mean contribution of the three meals, breakfast, lunch and dinner to daily protein intake was 14, 36 and 36%, to fat intake 17, 33 and 35% and to carbohydrate intake 23, 25 and 29%, respectively. Data on meal patterns are important in a comprehensive description of dietary habits of a population for a variety of reasons. PMID- 9989912 TI - Methodology of a survey on meal patterns in private senior households. AB - The methodology of a study on meal patterns is discussed. For data collection, menu records on the current diet over two periods of 6 weeks each and an additional self-administered questionnaire on various food related aspects were selected as instruments. Information is required concerning e.g. time, kind and frequency of meals during the day, kind and frequency of dishes consumed and the combination of these. The aim of the study is to obtain information about the nutritional behaviour of the elderly especially on meal patterns. These data are intended as the basis for menu plans reflecting actual nutritional habits in a diet, according to individual requirements, and not for assessing the participants' nutritional status. PMID- 9989913 TI - Eating patterns in French subjects studied by the "weekly food diary" method. AB - The "weekly food diary" was translated and adapted for use by French subjects. This validated method requires subjects to record every food and drink intake over 1 week, with several descriptors of the physical, psychological and social circumstances. Ten male [age 23. 6+/-2.3 years, body mass index (BMI) 20.7+/-0.6] and 16 female (age 23.3+/-0.6 years, BMI 20+/-0.6) students completed four weekly diaries over 1 year, one per season. Data were processed using a specially designed software. Breakfast was important, (about 400 kcalories). Lunch and dinner were almost equal in energy content but alcohol was consumed mainly with dinner. Meal size correlated positively with premeal hunger, number of people present, duration of premeal interval and time of day. Postmeal satiety correlated positively with meal size, aftermeal stomach content, and negatively with time of day, postmeal hunger and duration of sleep the preceding night. These observations allow hypotheses to be developed about mechanisms of intake in a French population and cross-cultural comparisons to be made. PMID- 9989914 TI - Food-based classification of eating episodes (FBCE). AB - The concept for categorization of eating episodes in dietary surveys was originally developed in studies of shift workers to compare "meal patterns" between night and day work shifts. The concept has been further improved through experience from applications in dietary surveys in other populations. In this paper, results from categorization of eating episodes in shift workers, elderly women and men during life transition periods, elderly female leg ulcer patients and obese men and their lean controls are shown and discussed. The categorization concept is based on seven food categories with food items of similar nutrient characteristics within each category. Each eating event is categorized as any of four types of "meals" or four types of "snacks" due to its combination of food categories. Thus, categorization is based on visible properties (food types) but at the same time reflecting invisible properties (nutrients). Criteria is also established to sub-categorize the "meal" types as being either "prepared" or "quick-prepared" from a behavioural perspective. Use of a defined and reliable concept for categorization is necessary to study eating episodes in dietary surveys, their determinants and also consequences on health and performance. Nocturnal eating during the circadian nadir might affect nutritional status. Since increasingly western populations appear to be moving from regular and planned meals to more episodic eating "around the clock", such analyses are of increasing interest in a bio-social perspective. PMID- 9989915 TI - From regional ethnographies to interdisciplinary approaches-research on meals in Finland. AB - The paper reviews Finnish research on meals and meal patterns since the turn of the century. The main research traditions and cases representing various methodological approaches-qualitative interview, health behaviour questionnaire and dietary survey-are discussed. In line with studies undertaken in other industrialized countries, the Finnish studies show that meal patterns are related to socio-economic structure, work schedules, lifecourse, living conditions and food availability. Meal patterns vary by individual energy needs, and the nutrient contents of meals can be different from those of snacks. It is difficult to account for all determinants and characteristics of meals in a single study. The three cases shed light on the various aspects of the meal. When planning an empirical study on meals the researcher should ask herself/himself at least four questions: (1) who defines the meal?; (2) are meal patterns assumed to vary by time and between subgroups of the study population?; (3) is information on nutrient content of various eating occasions relevant to the study?; and (4) could information on meals be obtained from existing data sources? PMID- 9989916 TI - Nordic meals: methodological notes on a comparative survey. AB - This article discusses some methodological aspects of the project "Eating and Modern Everyday Life. A Comparative Survey of Nordic Countries". Data were collected in April 1997 with computer assisted telephone interviews in Denmark, Finland, Norway and Sweden. Questionnaires included a record of the informant's eating on the day before the interview, attitudes related to current food discourses, socio-demographic information and a few open-ended questions. The emphasis was on social and cultural aspects of eating. One aim of this study is to investigate whether regular meals are substituted by irregular eating patterns. In order to avoid any predefined meal concepts the questionnaire therefore focused on eating events. The reconstruction of data is based on a model called the eating system. The model has three dimensions: the eating pattern (the rhythm and the number of eating events, the alternations of hot and cold eating events), the meal format (the composition of the main course, the sequence of the whole meal) and the social organization of eating (where and with whom people are eating, who did the cooking). Some preliminary results are presented suggesting that the questionnaire and the analytical model suit the purpose of studying modernization through the field of food. PMID- 9989917 TI - Evidence-based reduction of obesity: identification of a subculture's least fattening eating patterns. AB - Public health nutritional interventions, like clinical treatments in medicine or psychology, should be based on direct evidence of their efficacy relative to prior existing modalities. Yet the contribution of applied human nutrition and the psychology of eating to research into ways of slowing the rise of obesity has been limited to the intake of energy nutrients and investigator-prejudged questions about appetite and food choices. In contrast, it is feasible to get members of the public to describe their patterns of eating in their own words. Self-assessed current frequency of each common potentially less or more fattening eating pattern can then be used to associate weight change with changes in habit frequency. This design has been used to identify the long-term least fattening eating patterns retrospectively and prospectively in several studies in England and Germany. Without using assessments of usual nutrient intake, these studies demonstrate that the least fattening patterns over 1-2 or more years are drinks between meals with no energy intake, cutting back on fat in all foods and replacing as much sitting and riding as feasible each day with walking or cycling. An hypothesis to be tested by this method is that the only known automatic mechanism for eating less dessert is the learnt effect of boosting the readily digested carbohydrate content of high-energy main courses. Such evidence based advice as well as self-therapy for emotional eating and body-shape distress should be the front line of defence against unhealthy weight gain and re-gain. PMID- 9989918 TI - Evaluation of eating patterns with different methods: the Polish experience. AB - The implementation of a market economy at the beginning of the 1990s has changed Polish consumers. This paper describes results of different methods which are used to evaluate food consumption, including eating patterns, in this time of transition. Except for the significant decrease of dairy products and increase of vegetable oils the pattern of the menu in Poland remains very traditional. The differences between the previous and present situation are based on changes in the organization of shopping and the possibilities of preparing meals. PMID- 9989919 TI - Food habits in Kenya: the effects of change and attendant methodological problems. AB - Kenya, as a developing country, is in a process of transition between traditional and modern lifestyles. The population is dispersed by different ethnic, ecological and economical backgrounds. There are different food habits within the country and the traditions are influenced in different ways by modern influences, e. g. the media. The difficulties of studying food habits in such situations are described, and also the chances for nutrition studies. PMID- 9989920 TI - Assessment of adolescent food habits in Switzerland. AB - Several physical, psychological and behavioural changes may affect food habits during adolescence and have long-term consequences on adult health status. Also, as food habits are related to lifestyle and physical activity, all should be assessed together. This paper describes a self-administered food frequency questionnaire (FFQ) designed to assess semi-quantitatively food habits of adolescents, and evaluates its use in a study of lifestyle and physical activity. A FFQ was developed, tested in 20 adolescents and compared with a modified version of the diet history method (a combination of a 3-day dietary record and an interview with a dietitian). This validated semi-quantitative questionnaire was later included in a larger questionnaire on lifestyle and physical activity in a study of 3540 adolescents aged 9-19 years. In the validation study with 20 adolescents, the FFQ showed a good agreement with the modified version of the diet history. During the survey several consumption frequencies were found to be low. In the group of adolescents aged 14-19 years old, dairy products were consumed daily by less than 50% of the sample. About 53% girls but only 33% boys consumed one fruit daily. For one vegetable portion, these proportions were 17 and 8%, respectively. The self-administered food frequency questionnaire correctly describes food consumption in adolescents. Moreover, it was well accepted by the target group, easily understood and completed with very few problems. The results show that a significant proportion of adolescents didn>>t consume milk, fruit and vegetable on a daily basis. PMID- 9989921 TI - Interpretation of dietary change in the United States: fat as an indicator. AB - Measurement of dietary trends poses methodologic issues of great complexity and intellectural challenge. Confidence in the ability to draw inferences about trends increases when the results of various measurement methods point in the same direction, are of comparable magnitude and are consistent with one another as well as with external sources of related data. This paper illustrates these issues by reviewing inconsistencies in available data sources since the early 1970s on intake of fat in the United States. PMID- 9989922 TI - Predicting the intent to purchase unfamiliar and familiar cheeses: the effects of attitudes, expected liking and food neophobia. AB - The attitude model of the theory of reasoned action (TRA) has been applied mainly to predicting the choice of familiar foods; however, the choice of unfamiliar foods may be governed by distinct factors. In the present study, 92 females rated their attitudes and subjective norms about the purchase intentions of two familiar and two unfamiliar cheeses, and the expected and actual pleasantness of them. They also completed the food neophobia scale, which measures the tendency to avoid novel foods. Neophobic persons rated the attitudes and expected and actual taste pleasantness lower than neophilics for all cheeses, except for the most familiar, mild cheese. This suggests that food neophobia also indicates the tendency not only to avoid, but also to dislike novel foods. Before tasting, attitudes and subjective norms together predicted the intent to purchase familiar cheeses better (R2=0.54 and 0.58) than for novel cheeses (R2=0.24 and 0.35); thus, the basic TRA model was not as useful in predicting intent to purchase unfamiliar as familiar cheeses. The predictions especially for the novel cheeses were clearly improved by including expected pleasantness ratings in the model. The usefulness of the food neophobia score as an additional predictor was not clearly supported. Attitudes and subjective norms measured before tasting were poor predictors of purchase intents after tasting, which implies the importance of taste and direct product experience in food choice. PMID- 9989923 TI - Contemporary nutritional attitudes and practices: a factor analysis approach. AB - The results reported here are based upon a survey of the nutritional attitudes and practices of a sample of adults aged between 18 and 74 years. The scaled responses to two inventories of statements were subjected to a factor analysis in order to assess the extent to which it is possible to identify a set of coherent dimensions which underly the range of "surface" issues which figure consistently in the sociological literature. The results broadly confirm the utility of the inventories, and do suggest the presence of a series of underlying themes, some of which are very much along anticipated lines. However, one theme, that of deference to what might be thought of as "authoritative agencies" within the food system, was less expected, and deserves further attention. Additionally, selected factors were aggregated by summing the scores of their component variables, and correlated with the key independent variables of age, sex and social class, with a view to identifying the social profiles of their adherents. The results obtained were by no means clear cut, with a number of the anticipated features of such profiles being absent. Moreover, where the profiles were as anticipated, the correlations, although statistically significant, were relatively weak. This raised the issue of whether such an outcome was a methodological artefact, or a reflection of the possibility that differences in nutritional attitudes and practices are shaped by a range of lifestyle variables which do not coincide with conventional indicators of social differentiation. PMID- 9989924 TI - Restrained eating among vegetarians: does a vegetarian eating style mask concerns about weight? AB - The present study explored the relationships among dietary style (ranging from meat eating to veganism), cognitive restraint and feminist values. Two-hundred and twenty-seven participants with varying dietary styles completed the restraint subscale of the Three Factor Eating Questionnaire (TFEQ) and Attitudes Towards Feminism Scale (ATFS). Results indicated that among males, those who are high in cognitive restraint are more likely to exhibit a vegetarian dietary style than those low in cognitive restraint. Among women who are high in feminist values, those with high cognitive restraint are more likely to exhibit a vegetarian dietary style than those with low cognitive restraint, whereas for women low in feminist values those with high and low cognitive restraint are equally likely to exhibit vegetarian and non-vegetarian dietary styles. It is suggested that for some individuals, adoption of a vegetarian dietary style is an attempt to mask their dieting behaviour from others. PMID- 9989925 TI - Flavor preferences conditioned by intragastric nutrient infusions in rats fed chow or a cafeteria diet. AB - Numerous studies demonstrate that chow-fed rats learn to prefer flavors that are associated with the postingestive effects of nutrients. The rats>> limited dietary experience (i.e. only lab chow) may have facilitated preference learning because of the novelty of the training stimuli. This possibility was investigated by comparing nutrient conditioning in rats fed chow or a varied "cafeteria" diet. Rats in Experiment 1 were trained during alternate sessions (30 min/day) to drink two different flavors paired with concurrent intragastric infusions of 16% Polycose or water. Both diet groups displayed similarly strong preferences (89%) for and increased acceptance of the Polycose-paired flavor. A more demanding learning task was used in Experiment 2: new flavors were paired with delayed (15 min) infusions of Polycose or water. The chow and cafeteria groups both showed reduced, but comparable (78%, 77%) preferences for the Polycose-paired flavor. In Experiment 3, new flavors were paired with concurrent infusions of 7.1% corn oil or water. Again, the cafeteria and chow groups developed similar preferences for the nutrient-paired flavor (85%, 78%). Also, both groups preferred the Polycose paired flavor of Experiment 1 to the oil-paired flavor of Experiment 3 (76%, 78%). These results indicate that dietary variety does not interfere with nutrient-conditioned flavor preference learning in rats. PMID- 9989926 TI - Inhibition of anandamide hydrolysis by the enantiomers of ibuprofen, ketorolac, and flurbiprofen. AB - The endogenous cannabimimetic anandamide is hydrolyzed by a fatty acid amide hydrolase to yield arachidonic acid and ethanolamine. In the present study, the regional distribution of the activity and its sensitivity to inhibition by the enantiomers of ibuprofen, ketorolac, and flurbiprofen has been investigated. The rate of [3H]anandamide hydrolysis was found in both 7-week-old and 90-week-old rats to be in the order hippocampus > cerebral cortex > cerebellum > striatum approximately midbrain, with higher rates of hydrolysis for the 7-week-old rats than for the 90-week-old rats. In whole brain (minus cerebellum), the R(-) enantiomer of ibuprofen was a mixed-type inhibitor of anandamide hydrolysis and was approximately 2-3 times more potent than the S(+)-enantiomer, IC50 values of 230 and 750 microM, respectively, being found. A similar pattern of inhibition of anandamide hydrolysis was seen when intact C6 rat glioma cells were used. Ketorolac inhibited rat brain anandamide hydrolysis, with IC50 values of 50, 440, and 80 microM being found for the R-, S-, and R,S-forms, respectively. The IC50 value for R-flurbiprofen (60 microM) was similar to the IC50 value for the S enantiomer (50 microM). These data demonstrate that there is no dramatic enantiomeric selectivity of NSAID compounds as inhibitors of fatty acid amide hydrolase enzyme(s) responsible for the hydrolysis of anandamide. The enantiomers of flurbiprofen and R-ketorolac are the most potent NSAID inhibitors of fatty acid amide hydrolase yet reported. PMID- 9989927 TI - Activation of the P2Z/P2X7 receptor in human lymphocytes produces a delayed permeability lesion: involvement of phospholipase D. AB - Leukemic lymphocytes possess a cytolytic P2Z/P2X7 receptor which, when activated by extracellular ATP, opens a Ca2+- and Ba2+-permeable ion channel. This ATP stimulated influx of divalent cations has been shown to activate an intracellular phospholipase D (PLD) which hydrolyzes membrane phosphatidylcholine. Lymphocytes that were exposed to ATP for 20 min at 37 degrees C, washed, and then incubated without ATP for 2 h showed an increased uptake of propidium2+, a dye widely used to measure cytotoxicity. The potent P2Z/P2X7 receptor inhibitor, KN-62, which is known to prevent the channel opening when added with ATP, did not block development of the permeability lesion when added 15 min before dye addition. The activity of lymphocyte PLD was stimulated fourfold by ATP and a proportion of this increased activity persisted for several hours after removal of ATP. Loading lymphocytes with intracellular choline+ by prior incubation of cells with ATP in isotonic choline chloride abolished both ATP-stimulated PLD activity and the ATP induced permeability lesion. Addition of PLD but not phospholipase C to the extracellular medium increased lymphocyte permeability to propidium2+ and this effect was not observed in a choline medium. The cytolytic effect of exogenous PLD together with the inhibitory effect of choline, a product of the PLD reaction, suggests that sustained activation of intracellular PLD may be involved in the ATP-initiated cytolytic pathway. PMID- 9989928 TI - Allosteric regulation of type I hexokinase: A site-directed mutational study indicating location of the functional glucose 6-phosphate binding site in the N terminal half of the enzyme. AB - The Type I isozyme of mammalian hexokinase has evolved by a gene duplication fusion mechanism, with resulting internal duplication of sequence and ligand binding sites. However, 1:1 binding stoichiometry indicates that only one of these is available for binding the product inhibitor, Glc-6-P; the location of that site, in the N- or C-terminal half, remains under debate. Recent structural studies (Aleshin et al., Structure 6, 39-50, 1998; Mulichak et al., Nature Struct. Biol. 5, 555-560, 1998) implicated Asp 84 or its analog in the C-terminal half, Asp 532, in binding of Glc-6-P. Zeng et al. (Biochemistry 35, 13157-13164, 1996) demonstrated that mutation of Asp 532 to Lys or Glu did not affect inhibition by the Glc-6-P analog, 1,5-anhydroglucitol-6-P. These same mutations, as well as mutation to Ala, at the Asp 84 position are now shown to result in increased Ki for 1,5-anhydroglucitol-6-P. The ability of Pi to antagonize inhibition by the Glc-6-P analog is severely diminished or abolished by these mutations, suggesting that antagonism is dependent on precise positioning of the inhibitory hexose 6-phosphate. The structure of the enzyme complexed with Glc and Pi has been determined, and shows that Pi occupies the same site as the 6 phosphate group in the complex with Glc-6-P. Thus, antagonism between these ligands results from competition for a common anion binding site in the N terminal half. PMID- 9989929 TI - Influence of DNA binding on the degradation of oxidized histones by the 20S proteasome. AB - The 20S proteasome is localized in the cytosol and nuclei of mammalian cells. Previous work has shown that the cytosolic 20S proteasome is largely responsible for the selective recognition and degradation of oxidatively damaged cytosolic proteins. Since nuclear proteins are also susceptible to oxidative damage (e.g., from metabolic free radical production, ionizing radiation, xenobiotics, chemotherapy) we investigated the degradation of oxidatively damaged histones, in the presence and in the absence of DNA, by the 20S proteasome. We find that both soluble histones and DNA-bound histones are susceptible to selective proteolytic degradation by the 20S proteasome following mild oxidative damage. In contrast, more severe oxidative damage actually decreases the proteolytic susceptibility of histones. Soluble H1 showed the highest basal and maximal absolute proteolytic rates. Histone fraction H4 exhibited the greatest relative increase in proteolytic susceptibility following oxidation, almost 14-fold, and this occurred at a peroxide exposure of 5 mM. At the other end of the spectrum, histone H2A exhibited a maximal proteolytic response to H2O2 of only 6-fold, and this required an H2O2 exposure of 15 mM. An oxidation of reconstituted linear DNA plasmid-histone complex makes up to 95% of the histones bound to DNA susceptible to degradation, whereas undamaged protein-DNA complexes are not substrates for the proteasome. Severe oxidation by high concentrations of H2O2 appears to decreases the proteolytic susceptibility of histones due to the formation of cross-linked histone-DNA aggregates which appear to inhibit the proteasome. We conclude that the degradation of nuclear proteins is highly selective and requires prior damage of the substrate protein, such as that caused by oxidation. PMID- 9989930 TI - Inhibitory effects of streptozotocin, tumor necrosis factor-alpha, and interleukin-1beta on glucokinase activity in pancreatic islets and gene expression of GLUT2 and glucokinase. AB - Treatment of streptozotocin (ST), tumor necrosis factor-alpha (TNF-alpha), and interleukin-1beta (IL-1beta) resulted in destroying insulin-secreting beta-cells of pancreatic islets and impairment of islet glucose oxidation and glucose induced insulin secretion. IL-1beta and TNF-alpha inhibited insulin release and glucose utilization and oxidation. It was shown that the inhibitory effects of ST, IL-1beta, and TNF-alpha were due to impaired glucokinase activity. Glucokinase activity was severely impaired by ST, IL-1beta, and TNF-alpha treatments, as confirmed by assaying enzymes and nucleotides associated with glycolysis and glucose oxidation. On the other hand, nitric oxide was a factor of the deleterious effects of IL-1beta, TNF-alpha, and ST on pancreatic islets. Incubation of mouse pancreatic islets with ST at various concentrations of impairing insulin secretion resulted in generation of nitrite, stimulation of islet guanylyl cyclase and accumulation of cGMP, and inhibition of pancreatic islet mitochondrial aconitase activity to degree similar to those raised by IL 1beta and TNF-alpha. When the effects of IL-1beta and TNF-alpha on the gene expression of pancreatic GLUT2 and glucokinase were examined, the level of GLUT2 and glucokinase mRNA in pancreatic islets was significantly decreased. This suggested that IL-1beta and TNF-alpha downregulate gene expression of GLUT2 and glucokinase in pancreatic beta-cells. PMID- 9989931 TI - Effects of various amino acid 256 mutations on sarcoplasmic/endoplasmic reticulum Ca2+ ATPase function and their role in the cellular adaptive response to thapsigargin. AB - Upon direct selection of mammalian cells for resistance to thapsigargin (TG), a potent inhibitor of the sarcoplasmic/endoplasmic reticulum Ca2+ transport ATPase (SERCA), the ATPase can acquire specific mutations at amino acid position 256 (aa256). In particular, Phe256 --> Leu and Phe256 --> Ser substitutions can occur upon TG selection, with each substitution resulting in a SERCA that is 4- to 5 fold resistant to TG inhibition (M. Yu et al., J. Biol. Chem. 273, 3542-3546, 1998). We have now identified a third substitution, i.e., Phe256 --> Val, that occurs when the Chinese hamster lung fibroblast cell line DC-3F is selected for TG resistance. Although the Phe256 --> Val substitution at codon 256 results in a SERCA whose enzymological properties in terms of Ca2+ transport and ATP hydrolysis are essentially similar to that of wild-type (wt) SERCA, the mutant enzyme is more than 40-fold resistant to TG inhibition. To analyze further the role of aa256 in TG-SERCA interactions, mutational analysis of this particular residue was also carried out. Of all the mutations introduced, only the Phe256 - > Glu substitution interferes with expression of the ATPase. The Phe256 --> Arg substitution does not interfere with SERCA expression, but the resulting enzyme is totally inactive. In terms of sensitivity of the various mutants to TG, maximal reduction in the ATPase's affinity for TG occurs with amino acid substitutions containing branched side chains, i.e. with the Phe256 --> Val, Phe256 --> Ile, and Phe256 --> Thr mutants. Since a corresponding Phe is conserved in the Na+, K+-ATPase which is not sensitive to TG, our findings suggest that this amino acid provides stabilization of the stalk segment with respect to the membrane interface, thereby optimizing specific interactions of TG with neighboring S3 residues (L. Zhong and G. Inesi, J. Biol. Chem. 273, 12994 12998, 1998). It is likely that a relatively high frequency of codon 256 mutations favor the aa256 mutants as a specific adaptive response to TG selection. PMID- 9989932 TI - Bioreduction of Tempone and spin-labeled gentamicin by gram-negative bacteria: kinetics and effect of ultrasound. AB - The primary objective of this study is the investigation of bioreduction kinetics of hydrophilic spin probes, 2,2,6,6, -tetramethyl-4-oxo-piperidinyl-1-oxyl (Tempone), and spin-labeled antibiotic gentamicin by gram-negative bacteria maintained at various oxygen tensions, with emphasis on the effect of probe penetration rate. This information was used to evaluate the effect of ultrasound on the penetration of hydrophilic compounds, including antibiotics, into Pseudomonas aeruginosa and Escherichia coli cells. Penetration of spin-labeled compounds into the cells was assessed by the reduction rate of the nitroxyl moiety measured by EPR. In cell suspensions, both Tempone and spin-labeled gentamicin were localized predominantly in the aqueous phase surrounding the cells. However, a gradual reduction of the probes in contact with the cells indicated that the probes penetrated through the outer membrane and periplasmic space into the cytoplasmic membrane, where the electron transport chains and other metabolic activities of gram-negative bacteria are localized. The kinetics of probe reduction depended on oxygen tension and presence of electron transport chain blockers. It was found that probe penetration rate through the outer cell membrane affected the rate of probe reduction; damaging the permeability barrier by cell incubation with EDTA or by powerful insonation above the cavitation threshold increased the rate of probe reduction. In contrast, insonation below the cavitation threshold did not affect the rate of probe reduction. These findings imply that the recently observed synergistic effect between hydrophilic antibiotics and low frequency ultrasound in killing gram-negative bacteria did not result from the enhanced antibiotic penetration through bacterial cell walls. PMID- 9989933 TI - Structure and expression of the rat CYP3A1 gene: isolation of the gene (P450/6betaB) and characterization of the recombinant protein. AB - A P450 gene (P450/6betaB) of the CYP3A subfamily was isolated from a rat genomic library. Nucleotide sequencing of the exons revealed a high similarity with P450PCN1 cDNA (Gonzalez et al. (1985), J. Biol. Chem. 260, 7345-7441), but differed in 41 nucleotides, resulting in 11 changes and 2 deletions of amino acid residues. The P450/6betaB spanned about 30 kbp and consisted of 13 exons, and was in exon number and size identical with CYP3A2 gene except in the 6th exon, which was shorter than that of CYP3A2. 6beta-B mRNA, which may be transcribed from P450/6betaB, was detected on Northern blotting and by reverse transcription polymerase chain reaction (RT-PCR). Profiles of the developmental change and induction by a treatment with several chemicals were very similar to those of P450PCN1 mRNA reported previously. P450PCN1 mRNA and gene, however, were not detected by PCR in rats. To determine whether P450/6betaB encodes an active protein, a cDNA was isolated and expressed. Expression of 6beta-B cDNA in COS-1 cells was carried out and revealed that the recombinant protein comigrated with purified P4506beta-4 previously identified as CYP3A1. The recombinant 6beta-B protein showed similar turnover rate and regioselectivity for testosterone with purified P4506beta-4 by the simultaneous addition of NADPH-cytochrome P450 reductase and cytochrome b5. These data suggest that P450/6betaB encodes an active P450 form corresponding to CYP3A1 and P450PCN1 reported previously does not exist in rats. PMID- 9989934 TI - Properties of the His57-Asp102 dyad of rat trypsin D189S in the zymogen, activated enzyme, and alpha1-proteinase inhibitor complexed forms. AB - Structural and biochemical studies suggest that serpins induce structural rearrangements in their target serine-proteinases. Previous NMR studies of the complex between a serpin, alpha1-proteinase inhibitor, and a mutant of recombinant rat trypsin (the Asp189 to Ser mutant, D189S, which is much more stable than wild-type rat trypsin against autoproteolysis) provided information about the state of catalytic residues in this complex: the hydrogen bond between Asp102 and His57 remains intact in the complex, and spectral properties of His57 are more like those of the zymogen than of the activated enzyme (G. Kaslik, et al., 1997, Biochemistry 36, 5455-5464). Here we report the protonation and exchange behavior of His57 of recombinant rat trypsin D189S in three states: the zymogen, the active enzyme, and the complex with human alpha1-proteinase inhibitor and compare these with analogous behavior of His57 of bovine chymotrypsinogen and alpha-chymotrypsin. In these studies the pKa of His57 has been determined from the pH dependence of the 1H NMR signal from the Hdelta1 proton of histidine in the Asp102-His57 dyad, and a measure of the accessibility of this part of the active site has been obtained from the rate of appearance of this signal following its selective saturation. The activation of rat trypsinogen D189S (zymogen, pKa = 7.8 +/- 0.1; Hill coefficient = 0. 86 +/- 0.05) decreased the pKa of His57 by 1.1 unit and made the protonation process cooperative (active enzyme, pKa = 6.7 +/- 0.1; Hill coefficient = 1.37 +/- 0.08). The binding of alpha1-proteinase inhibitor to trypsin D189S led to an increase in the pKa value of His57 to a value higher than that of the zymogen and led to negative cooperativity in the protonation process (complex, pKa = 8.1 +/- 0. 1; Hill coefficient = 0.70 +/- 0.08), as was observed for the zymogen. In spite of these differences in the pKa of His57 in the zymogen, active enzyme, and alpha1 proteinase inhibitor complex, the solvent exchange lifetime of the His57 Hdelta1 proton was the same, within experimental error, in all three states (lifetime = 2 to 12.5 ms). The linewidth of the 1H NMR signal from the Hdelta1 proton of His57 was relatively sharp, at temperatures between 5 and 20 degrees C at both low pH (5.2) and high pH (10.0), in spectra of bovine alpha-chymotrypsin, recombinant rat trypsin D189S, and the complex between rat trypsin D189S and human alpha1 proteinase inhibitor; however, in spectra of the complex between alpha chymotrypsin and human alpha1-proteinase inhibitor, the peak was broader and could be well-resolved only at the lower temperature (5 degrees C). PMID- 9989935 TI - Purification and characterization of two amine N-sulfotransferases, AST-RB1 (ST3A1) and AST-RB2 (ST2A8), from liver cytosols of male rabbits. AB - Two sulfotransferases (STs), designated as AST-RB1 (ST3A1) and AST-RB2 (ST2A8), with high a amine N-sulfonating activity, were purified from male rabbit liver cytosols. AST-RB1 and AST-RB2 were purified to homogeneity by the anion-exchange, affinity, and hydroxyapatite chromatography. The N-terminus of both enzymes were blocked. The subunit molecular mass of both enzymes was estimated to be 34 kDa on SDS-PAGE. AST-RB1 efficiently catalyzed N-sulfonation of alicyclic, alkyl, and arylamines such as 4-phenyl-1,2,3, 6-tetrahydropyridine, 1-[(5-chloro-2-oxo-3(2H) benzothiazolyl)acetyl]-piperazine, desipramine, and aniline, whereas its catalytic activities toward 2-naphthol and dehydroepiandrosterone (DHEA) were very low. On the other hand, AST-RB2 efficiently catalyzed sulfonation of desipramine and DHEA, but had no activity toward 2-naphthol. Amino acid sequences of peptide fragments derived from the purified AST-RB1 showed no significant homology with previously reported STs, but those from the purified AST-RB2 shared a high similarity with those of the ST2 family. Both enzymes were expressed specifically in the liver. The present results strongly suggest that the purified AST-RB1 is a novel enzyme in terms of structure and catalytic properties showing high selectivity for amine substrates, and AST-RB2 is a quite unique from among ST2A enzymes of other species in its substrate specificity. PMID- 9989936 TI - The proteolytic maturation of prohormone convertase 2 (PC2) is a pH-driven process. AB - Recombinant proPC2 purified from the medium of CHO cells overexpressing both the prohormone convertase (PC) precursor proPC2 and the 21-kDa amino terminal portion of the neuroendocrine protein 7B2 can spontaneously convert to an active species. In the present report, we have characterized the proPC2 zymogen conversion process. Sequencing of the mature 66 kDa enzyme revealed a single site of cleavage at the paired basic site amino terminal to the GYRDI sequence. In contrast to mature PC2 activity, proPC2 conversion was inhibited neither by the eukaryotic subtilisin inhibitor pCMS nor by the specific PC2 inhibitor, 7B2 CT peptide, suggesting significant differences between the proPC2 conversion reaction and the hydrolysis of synthetic substrates by mature PC2. In support of this idea, proPC2 conversion was not calcium dependent and was unaffected by 5 mM EDTA. The rate of conversion of proPC2 remained similar with a 10-fold difference in zymogen concentration, implicating an intramolecular rather than intermolecular mechanism of activation. Interestingly, the rate of proPC2 conversion was extremely pH dependent, occurring most extensively between pHs 4.0 and 4.9. Taken together, our results suggest that cellular proPC2 maturation occurs via an autocatalytic, intramolecular process controlled not by 7B2 inhibition nor by calcium levels, but by the decreasing pH gradient along the secretory pathway. PMID- 9989937 TI - Modulation of the PA28alpha-20S proteasome interaction by a peptidyl alcohol. AB - The peptidyl alcohol N-benzyloxycarbonyl-Ile-Glu(O-t-Bu)-Ala-leucinol is a mild activator of the chymotrypsin-like activity of the proteasome. When added to an incubation mixture of recombinant PA28alpha plus 20S proteasome the peptidyl alcohol antagonizes the stimulation of the chymotrypsin-like activity by PA28alpha in a dose-dependent manner (IC50 = 30 microM). This effect is selective for the chymotrypsin-like activity. Stimulation of the peptidyl-glutamyl peptide bond hydrolyzing activity of the proteasome by PA28alpha is not affected by the peptidyl alcohol. The ovalbumin immunodominant epitope SIINFEKL is hydrolyzed by the PA28alpha-activated 20S proteasome to SIINF and SIINFE in approximately equimolar amounts. Addition of the peptidyl alcohol to an incubation mixture of PA28alpha, 20S proteasome and SIINFEKL shifts the ratio of products in favor of SIINFE. A similar shift in favor of postglutamyl cleavages occurs with the extended peptide LEQLESIINFEKLTE. By altering the ratio of products produced by the PA28alpha-activated proteasome, the peptidyl alcohol acts as a proteasome modulator. Proteasome modulators represent a novel class of molecules with a potential for altering the processing of antigens by the PA28-proteasome complex for presentation by the MHC class I system. PMID- 9989938 TI - Kinetic analysis of spermine binding to NRD convertase. AB - N-arginine dibasic convertase cleaves polypeptides between paired basic residues containing the sequence Arg-Arg or Arg-Lys. The enzyme contains a large anionic domain, which in the rat enzyme consists of 57 acidic residues out of a stretch of 76 amino acids. Polyamines modulate the activity of the enzyme presumably by binding at the anionic domain (Csuhai et al. (1995) Biochemistry 34, 12411 12419). In this study a kinetic analysis of the effect of salts and amines, particularly the polyamine spermine, on the rat enzyme was studied. Simple salts were inhibitory with no apparent specificity for the anion or cation. Inhibition resulted in an increased Km and a decreased Vmax. Evidence that amines bind to an anionic domain was obtained by the finding that N,N-bis [2-hydroxyethyl]-2 aminoethanesulfonic acid, which is structurally related to the inhibitory amine triethanolamine, is noninhibitory. Inhibition exhibited a complex dependence on spermine concentration. The data fit a model in which enzyme-spermine and enzyme (spermine)2 complexes are formed. A pH-independent Kd ( approximately 0.1 microM) was obtained for enzyme-spermine formation, while enzyme-(spermine)2 formation was dependent on pH; Kd at pH 6.5 = 1 microM and a Kd at pH 8 = approximately 16 microM. Direct binding of spermine was demonstrated by the ability of spermine to increase the thermal stability of the enzyme. The concentration dependence for the spermine-induced increase in thermal stability fits a model in which formation of the enzyme-spermine complex is sufficient to account for the observed changes. PMID- 9989939 TI - Two progesterone-dependent endometrial nuclear factors bind to an E-box in the rabbit uteroglobin gene promoter: involvement in tissue-specific transcription. AB - We studied the implications of progesterone-dependent transcription factors in the hormonal and tissue-specific induction of the uteroglobin gene (ug) in the rabbit endometrium. Previously, we have observed the interaction of two progesterone-dependent endometrial nuclear proteins (TRBPs) with sequences downstream from the ug TATA box. Using electrophoretic mobility shift assays (EMSA) we show here that TRBPs specifically interacted with an E-box localized almost immediately downstream from the ug TATA box. UV crosslinking of affinity purified TRBPs to the radiolabeled oligonucleotide probe confirmed that these factors were proteins with molecular mass of about 40-50 kDa. Ferguson's analysis of the Mr of the DNA-TRBP complexes suggested that TRBPs interacted with the E box either as homo- or heterodimers. This interaction did not result in detectable bending of the DNA. EMSA analysis with nuclear extracts from different rabbit tissues suggested that TRBPs might be endometrium-specific nuclear factors. Involvement of the E-box in the tissue-specific transcription from the ug promoter was assessed by transient expression experiments using different cell lines transfected with a reporter gene driven by the ug promoter which contained either the intact E-box or a mutated version that completely abolished its interaction with TRBPs. These experiments indicated that, in all cell lines of nonendometrial lineage, destruction of the E-box increased transcription from the ug promoter, whereas in two cell lines of endometrial origin this mutation either had no appreciable effect or slightly reduced the transcription from the promoter. Thus, this E-box and endometrial helix-loop-helix proteins might be involved in the hormonal and tissue-specific regulation of ug transcription. PMID- 9989940 TI - Concurrent increase of oxidative DNA damage and lipid peroxidation together with mitochondrial DNA mutation in human lung tissues during aging--smoking enhances oxidative stress on the aged tissues. AB - Although mutation of mitochondrial DNA (mtDNA) in human tissues has been established to associate with intrinsic aging, the impact of environmental factors on the formation and accumulation of mtDNA mutations and oxidative DNA damage in human tissues is poorly understood. We have investigated the levels of mtDNA with the 4977-bp deletion and A3243G point mutation, oxidative DNA damage (indicated by the formation of 8-hydroxy-2'-deoxyguanosine, 8-OH-dG), and lipid peroxides in lung tissues from smokers and nonsmokers of subjects of different ages. The results showed concurrent age-dependent increase of the 4977-bp deleted mtDNA (P < 0.001), 8-OH-dG (P < 0.05), and lipid peroxides (P < 0.05) in the human lung. In the group of subjects above 60 years old, smokers had more extensive DNA damage and lipid peroxidation than did the nonsmokers. However, the levels of mtDNA with the 4977-bp deletion and A3243G point mutation in the lung of smokers were not significantly different from those of the age-matched nonsmokers. Taken together, these results suggest that accumulation of mtDNA with the 4977-bp deletion together with oxidative DNA damage and lipid peroxides is associated with aging and that smoking enhances oxidative damage in human lung tissues. PMID- 9989941 TI - Glucocorticoids stimulate CREB binding to a cyclic-AMP response element in the rat serine dehydratase gene. AB - Transcription of the rat serine dehydratase (SDH) gene, which is stimulated in hepatocytes by glucagon through the activity of the second messenger, cAMP, is augmented by pretreatment with glucocorticoids. A putative cAMP response element (CRE) located approximately 3.5 kbp upstream of the transcriptional start site was hypothesized to be responsible for this effect. Here we have demonstrated by DNaseI footprinting and site-directed mutagenesis that the phosphorylated cAMP response element binding protein (CREB) binds to a cAMP response element different from that described previously. While the amount of CREB in the extracts is unaltered by hormone treatment, more CREB is capable of binding the response element upon addition of dexamethasone (Dex). These studies suggest that synergistic induction of the SDH gene by cAMP and Dex is through a CRE and is due, in part, to regulation of CREB-DNA binding by treatment of the cells with glucocorticoids. PMID- 9989942 TI - Conformational changes in the 20S proteasome upon macromolecular ligand binding analyzed with monoclonal antibodies. AB - Proteasomes interact with a variety of macromolecular ligands that modulate their ability to degrade peptide and protein substrates. The effector PA28 increases the peptidase activities of proteasomes whereas HSP90 and alpha-crystallin inhibit a peptide-hydrolyzing activity. Four monoclonal antibodies were used as probes to detect conformational changes of proteasome subunits. Conformational changes in alpha- or beta-subunits were found upon binding PA28, HSP90, alpha crystallin, and the substrate casein but not with the peptide substrate analogs calpain inhibitor 1 (Ac-Leu-Leu-norleucinal), calpain inhibitor 2 (Ac-Leu-Leu methioninal), or MG 132 (N-Cbz-Leu-Leu-leucinal). PMID- 9989943 TI - Molecular crowding and viscosity as determinants of translational diffusion of metabolites in subcellular organelles. AB - The role of molecular crowding and viscosity on the apparent translational diffusion coefficient (ADC) of small metabolites was investigated in different subcellular organelles using the pulse-field gradient spin-echo 1H NMR technique. ADCs of metabolites with increasing radius of gyration (0.7 A < RG < 4.5 A) were measured in the cytoplasm of rat or chicken erythrocytes, in the nucleus of chicken erythrocytes, and in isolated rat liver mitochondria. Metabolite ADCs in these systems were compared with the corresponding ADCs determined in model solutions of increasing bulk viscosity but different molecular crowding. For solutions having the same viscosity, metabolite ADCs decreased with increasing concentration of cosolutes. This effect is adequately described by the modified Stokes-Einstein relationship, ADC = k/RG (1 + 2.5Phi), where k is a constant for a given temperature and Phi is an obstruction factor reporting the fractional volume of solution occupied by cosolutes, a measure of the molecular crowding in the solution. Cytoplasmic values of Phi for metabolites of different sizes did not depend exclusively on metabolite RG but on additional factors including the chemical nature of the metabolite, the presence of diffusional barriers, and metabolite-specific binding sites. In the case of water, nuclear Phi values approached those of the extracellular space while mitochondrial Phi values were significantly higher than those of the cytoplasm. Taken together, these results reveal important differences in molecular crowding within the different subcellular compartments, suggesting considerable diffusional heterogeneity for small metabolites within the different intracellular organelles. PMID- 9989944 TI - Purification and properties of mycobacterial GDP-mannose pyrophosphorylase. AB - The enzyme that catalyzes the formation of GDP-d-mannose from GTP and alpha-d mannose-1-P was purified about 2300-fold to near homogeneity from the soluble fraction of Mycobacterium smegmatis. At the final stage of purification, a major protein band of 37 kDa was observed and this band was specifically labeled, and in a concentration-dependent manner, by the photoaffinity probe 8-N3-GDP[32P]-d mannose. The purified enzyme was stable for several months when kept in the frozen state. The 37-kDa band was subjected to protein sequencing and one peptide sequence of 25 amino acids showed over 80% identity to GDP-mannose pyrophosphorylases of pig liver and Saccharomyces cerevesiae. In contrast to some other bacterial GDP-mannose pyrophosphorylases, the mycobacterial enzyme was not multifunctional and did not have phosphomannose isomerase or phosphoglucose isomerase activity. Also, in contrast to the pig liver enzyme which uses mannose 1-P or glucose-1-P plus GTP to synthesize either GDP-mannose or GDP-glucose, the mycobacterial enzyme was specific for mannose-1-P as the sugar phosphate substrate. The enzyme was also relatively specific for GTP as the nucleoside triphosphate substrate. ITP was about 18% as effective as GTP, but ATP, CTP, and UTP were inactive. The activity of the enzyme was inhibited by GDP-glucose and glucose-1-P, although neither was a substrate for this enzyme. The pH optimum for the enzyme was 8.0, and Mg2+ was the best cation with optimum activity at about 5 mM. This enzyme is important for producing the activated form of mannose for formation of cell wall lipoarabinomannan and various mannose-containing glycolipids and polysaccharides. PMID- 9989945 TI - Purification and cloning of a thermostable manganese catalase from a thermophilic bacterium. AB - We have purified a heat-stable catalase from a thermophilic bacterium, Thermus species strain YS 8-13. The enzyme was purified 160-fold from crude cellular extracts and possessed a specific activity of 8000 units/mg at 65 degrees C. The purified enzyme displayed the highest activity at pH 7 to 10 and temperatures around 85 degrees C. The catalase was determined to be a manganese catalase, based on results from atomic absorption spectra and inhibition experiments using sodium azide. The enzyme was composed of six identical subunits of molecular weight 36,000. Amino acid sequences determined from the purified protein were used to design oligonucleotide primers, which were in turn used to clone the coding gene. The nucleotide sequence of a 1.4-kb fragment of Thermus sp. YS 8-13 genomic DNA containing a 909-bp open reading frame was determined. The gene encoded a 302-residue polypeptide of deduced molecular weight 33,303. The deduced amino acid sequence displayed a region-specific homology with the sequences of the manganese catalase from a mesophilic organism, Lactobacillus plantarum. PMID- 9989946 TI - The dissociation rate of a winged helix protein-DNA complex is influenced by non DNA contact residues. AB - The dissociation constants and the half-lives of the DNA complexes of winged helix protein Genesis and its mutants were investigated. Our data show that substitutions of non-DNA contact residues in the two highly dynamic wing sequences dramatically change the off rates of the complexes. Thus, our data indicate that the off rate of a DNA complex is encoded in the amino acid sequence of the DNA-binding protein and/or should be a unique property for a protein-DNA complex. Our data also indicate that the local structural transition of a DNA binding protein in its DNA recognition process is likely to go through a transition state, which can control the on and off rates of a complex. PMID- 9989947 TI - Inhibition of 3C protease from human rhinovirus strain 1B by peptidyl bromomethylketonehydrazides. AB - The gene coding for the 3C protease from human rhinovirus strain 1B was efficiently expressed in an Escherichia coli strain which also overexpressed the rare argU tRNA. The protease was isolated from inclusion bodies, refolded, and exhibited a kcat/Km = 3280 M-1 s-1 using an internally quenched peptidyl fluorogenic substrate. This continuous fluorogenic assay was used to measure the kinetics of 3C protease inhibition by several conventional peptidyl chloromethylketones as well as a novel series of compounds, the bromomethylketonehydrazides. Compounds containing the bromomethylketonehydrazide backbone and a glutamine-like side chain at the P1 position were potent, time dependent inhibitors of rhinovirus 3C protease with kinact/Kinact values as high as 23,400 M-1 s-1. The inhibitory activity of compounds containing modified P1 side chains suggests that the interactions between the P1 carboxamide group and the 3C protease contributes at least 30-fold to the kinact/Kinact rate constants for bromomethylketonehydrazide inhibition of 3C protease. Electrospray ionization mass spectrometry measurements of the molecular weights of native and inhibited 3C protease have established an inhibitory mechanism involving formation of a covalent adduct between the enzyme and the inhibitor with the loss of a bromide ion from the bromomethylketonehydrazide. Tryptic digestion of bromomethylketonehydrazide-inhibited 3C protease established adduct formation to a peptide corresponding to residues 145-154, a region which contains the active site cysteine-148 residue. The bromomethylketonehydrazides were fairly weak inhibitors of chymotrypsin, human elastase, and cathepsin B and several of these compounds also showed evidence for inhibition of human rhinovirus 1B replication in cell culture. PMID- 9989948 TI - Latency of varicella zoster virus; a persistently perplexing state. AB - Varicella zoster virus (VZV) is the herpesvirus which causes the childhood disease varicella, also known as chickenpox, and the adult disease herpes zoster, also known as shingles. These distinct diseases are separated by a lengthy period of latency, often lasting decades, in which the virus resides within the ganglia of the host. VZV latency and reactivation from it have, for the most part, been extraordinarily difficult to examine. This is due to the lack of a good animal model for the VZV latent state, the inability to experimentally reactivate VZV under any circumstances and the caveats and problems encountered in examining human ganglionic tissue. However, insights into features of the molecular events of VZV latency have been gleaned from its pathogenesis and from recent advances in molecular probing of human and animal ganglia. Evidence suggests that the latent VZV genome may express transcripts unlike those of closely related herpesviruses, and some evidence suggests an unusual site for the establishment of VZV latency. In this review, the current evidence for events occurring during the VZV latent state will be discussed, from a view of its pathogenesis as well as its molecular biology. PMID- 9989949 TI - Signal transduction by fibroblast growth factor receptors. AB - The fibroblast growth factor family, with its prototype members acidic FGF (FGF 1) and basic FGF (FGF-2), binds to four related receptor tyrosine kinases, expressed on most types of cells in tissue culture. In many respects, the FGF receptors appear similar to other growth factor receptors. Thus, dimerization of receptor monomers upon ligand binding is likely to be a requisite for activation of the kinase domains, leading to receptor trans phosphorylation. FGF receptor-1 (FGFR-1), which shows the broadest expression pattern of the four FGF receptors contains at least seven tyrosine phosphorylation sites. A number of signal transduction molecules are affected by binding with different affinities to these phosphorylation sites. The potential roles of these signal transduction molecules in FGF-induced biological responses and in pathological processes are discussed. PMID- 9989950 TI - Polyomaviruses and human tumors: a brief review of current concepts and interpretations. AB - Polyomaviruses are small DNA viruses that typically establish persistent but inapparent infections of their natural hosts, although cytolytic disease may develop if the host becomes immunocompromised. Most polyomaviruses have the ability to induce tumor formation when introduced into certain foreign hosts and are considered oncoviruses. Some polyomaviruses, including those that infect humans, have occasionally been detected in cancerous tissue of their natural hosts. This article briefly reviews the biology of polyomaviruses and explores issues pertaining to the significance of association of polyomaviruses with human tumors. PMID- 9989951 TI - Biological significance of the expression of urokinase-type plasminogen activator receptors (uPARs) in brain tumors. AB - The urokinase-type plasminogen activator receptor (uPAR) plays a critical role in the regulation of cell-surface plasminogen activation in several physiological and pathological conditions. Recent evidence suggests that the uPAR is also involved in processes that are not related to plasminogen activation, including cell adhesion and transmission of extracellular signals across the plasma membrane. The uPAR influences cell migration and spreading both in vivo and in vitro through the cell-surface activation of plasminogen. The uPAR can bind to vitronectin, an adhesive extracellular matrix protein that contains the Arg-gly Asp (RGD) cell adhesion domain and that serves as a ligand for several integrin receptors. uPAR also forms complexes with (1, (2, and (3 integrins, thereby allowing mutual interactions and regulation between cell adhesion and proteolysis. Recently, uPAR has been shown to have strong prognostic value for predicting disease recurrence and overall survival in certain types of cancer. We discuss here the biological significance of uPAR in the glioblastoma invasion process. Strong correlations found between elevated uPAR levels in glioblastoma cells and tumor invasiveness have led to uPAR being selected as a target for therapy in experimental animal models. Using antisense vectors to down regulate uPAR expression at the level of the mRNA and protein in glioblastoma cells, has been shown to inhibit tumor formation in nude mice. These results provide a potential basis from which to develop novel therapeutic strategies to direct the expression of antisense uPAR and to evaluate the efficiency of this technique for cancer gene therapy in patients with brain tumor. PMID- 9989952 TI - Transcutaneous electrohepatogram in humans. AB - We could recently characterize a normal "electrohepatogram" (EHG) in a canine model. It consisted of monophasic positively deflected slow waves or pacesetter potentials (PPs). A "dysrhythmic EHG" was produced when the liver was insulted by hepatic vessel clamping or liver irradiation. The postulation that electrohepatography might act as an investigative tool in liver diseases prompted the author to develop the EHG percutaneously in humans. 23 healthy volunteers (16 men, 7 women; mean age 38.6 years) and 13 patients (8 men, 5 women; mean age 34.2 years) with huge supraumbilical ventral hernia were studied. The liver was exposed during the ventral hernia repair and 3 electrodes were sutured to the liver capsule. The optimal position for percutaneous recording was identified. The 3 electrodes were placed, 5 cm apart, on a transverse line, parallel to and 1.5-2 cm below, the costal margin. PPs were recorded from the 3 electrodes applied directly to the liver and from those applied to the skin. The wave was monophasic and positively deflected with a mean frequency of 8.3 cycle/s and amplitude of 56.5 microV. The PPs had the same frequency and amplitude from the 3 electrodes applied to the same subject. The percutaneously recorded waves were identical with those recorded directly from the liver. A percutaneous EHG could be characterized for the normal liver in humans. It might show changes in liver diseases and thus act as an investigative tool in the diagnosis of such conditions. PMID- 9989953 TI - The role of integrins in the malignant phenotype of gliomas. AB - Integrins are cell surface receptors that mediate the physical and functional interactions between a cell and its surrounding extracellular matrix (ECM). Expressed as heterodimers, the specific alpha or beta chains that constitute the integrin receptor determine the repertoire of ECM proteins to which a specific integrin may bind (table 1). While classically, the role ascribed to integrins has been that of anchoring cells to the ECM, the more contemporary spectrum of integrin function greatly exceeds that of mere cell adhesion. Recent reports have demonstrated that the interaction between the ECM and cell surface integrins leads to intracellular signaling events that affect cell migration, proliferation, and survival, which in the context of neoplastic cells, can translate directly into the malignant phenotype (1). Indeed, the role of specific integrins in tumorigenesis has been demonstrated in numerous cancer types (table 2). In primary tumors of the nervous system, the contribution of integrins to the malignant phenotype of gliomas has been an area of significant attention and research in numerous laboratories, including that of ours. As illustrated in table 3, several integrins have been identified as being of key importance in glioma biology. In this article, we review the current knowledge of how these integrins influence the malignant characteristics of gliomas and, as such, how these cell surface receptors may thus represent potential targets in the design of future therapeutics for patients afflicted with gliomas. PMID- 9989954 TI - Prediction of myocardial viability by MRI. PMID- 9989955 TI - Dobutamine MRI: A serious contender in pharmacological stress imaging? PMID- 9989956 TI - Dietary prevention of coronary heart disease: the Lyon Diet Heart Study. PMID- 9989957 TI - Influence of low HDL on progression of coronary artery disease and response to fluvastatin therapy. AB - BACKGROUND--Patients with coronary artery disease (CAD) commonly have low HDL cholesterol (HDL-C) and mildly elevated LDL cholesterol (LDL-C), leading to uncertainty as to whether the appropriate goal of therapy should be lowering LDL C or raising HDL-C. METHODS AND RESULTS--Patients in the Lipoprotein and Coronary Atherosclerosis Study (LCAS) had mildly to moderately elevated LDL-C; many also had low HDL-C, providing an opportunity to compare angiographic progression and the benefits of the HMG-CoA reductase inhibitor fluvastatin in patients with low versus patients with higher HDL-C. Of the 339 patients with biochemical and angiographic data, 68 had baseline HDL-C <0.91 mmol/L (35 mg/dL), mean 0.82+/ 0.06 mmol/L (31. 7+/-2.2 mg/dL), versus 1.23+/-0.29 mmol/L (47.4+/-11.2 mg/dL) in patients with baseline HDL-C >/=0.91 mmol/L. Among patients on placebo, those with low HDL-C had significantly more angiographic progression than those with higher HDL-C. Fluvastatin significantly reduced progression among low-HDL-C patients: 0.065+/-0.036 mm versus 0.274+/-0.045 mm in placebo patients (P=0.0004); respective minimum lumen diameter decreases among higher-HDL-C patients were 0. 036+/-0.021 mm and 0.083+/-0.019 mm (P=0.09). The treatment effect of fluvastatin on minimum lumen diameter change was significantly greater among low-HDL-C patients than among higher-HDL-C patients (P=0.01); among low-HDL C patients, fluvastatin patients had improved event-free survival compared with placebo patients. CONCLUSIONS--Although the predominant lipid-modifying effect of fluvastatin is to decrease LDL-C, patients with low HDL-C received the greatest angiographic and clinical benefit. PMID- 9989958 TI - Early contrast-enhanced MRI predicts late functional recovery after reperfused myocardial infarction. AB - BACKGROUND: We have observed 3 abnormal patterns on contrast-enhanced MRI early after reperfused myocardial infarction (MI): (1) absence of normal first-pass signal enhancement (HYPO), (2) normal first pass signal followed by hyperenhanced signal on delayed images (HYPER), or (3) both absence of normal first-pass enhancement and delayed hyperenhancement (COMB). This study examines the association between these patterns in the first week after MI and late recovery of myocardial contractile function by use of magnetic resonance myocardial tissue tagging. METHODS AND RESULTS: Seventeen patients (14 men) with a mean age of 53+/ 12 years were studied after a reperfused first MI. Contrast-enhanced images were acquired immediately after bolus administration of gadolinium and 7+/-2 minutes later. Tagged images were acquired at weeks 1 and 7. Circumferential segment shortening (%S) was measured in regions displaying HYPER, COMB, or HYPO contrast patterns and in remote regions (REMOTE) at weeks 1 and 7. At week 1, %S was depressed in HYPER, COMB, and HYPO (9+/-8%, 7+/-6%, and 5+/-4%, respectively) and were less than REMOTE (18+/-6%, P<0.003). However, in HYPER, %S improved at week 7 from 9+/-8% to 18+/-5% (P<0.001 versus week 1). In contrast, HYPO did not improve significantly (5+/-4% to 6+/-3%, P=NS) and COMB tended to improve 7+/-6% to 11+/-6% (P=0.06). CONCLUSIONS: HYPER has partially reversible dysfunction and represents predominantly viable myocardium. COMB shows borderline improvement and likely contains an admixture of viable and necrotic myocardium. HYPO shows little functional improvement at 7 weeks, presumably because of irreversible myocardial damage. PMID- 9989959 TI - Automated heparin-delivery system to control activated partial thromboplastin time: evaluation in normal volunteers. AB - BACKGROUND: Unfractionated heparin is used widely; however, control of the level of anticoagulation remains its greatest problem, with fewer than 35% of patients having activated partial thromboplastin times (aPTTs) within a range of 55 to 85 seconds in recent trials. METHODS AND RESULTS: We developed and tested a prototype of an automated heparin control system (AutoHep) in which a computer based titration algorithm adjusted the heparin infusion to reach a target aPTT. In 1 study, 12 healthy male subjects received an intravenous infusion of heparin with the rate determined by AutoHep and were randomized to receive an initial bolus or no bolus of heparin preceding the infusion. A second study evaluated the automated blood sampling system in 12 subjects. Of the 344 end-point aPTT measurements, 78% were within +/-10 seconds of the target (prespecified primary end point), and 89% were within a +/-15-second range. The time to achieve a target aPTT was 93 minutes without and 150 minutes with an initial heparin bolus. The total percentage of time within the target range +/-15 seconds was 46 of 48 hours (96%). The automatic blood sampling system successfully obtained 96% of all scheduled samples. CONCLUSIONS: These results suggest that the AutoHep system has the potential to significantly improve aPTT control of intravenous heparin compared with current clinical practice. PMID- 9989960 TI - Long-term prognostic value of dobutamine-atropine stress echocardiography in 1737 patients with known or suspected coronary artery disease: A single-center experience. AB - BACKGROUND: The purpose of this study was to assess the long-term value of dobutamine-atropine stress echocardiography (DSE) for prediction of late cardiac events in patients with proven or suspected coronary artery disease. METHODS AND RESULTS: Clinical data and DSE results were analyzed in 1734 consecutive patients undergoing DSE between 1989 and 1997. Seventy-four patients who underwent revascularization within 3 months of DSE and 1 patient lost to follow-up were excluded; the remaining 1659 (median age, 62 years; range, 14 to 99 years) were followed up for 36 months (range, 6 to 96 months). Wall motion abnormalities at rest and the presence and extent of stress-induced wall motion abnormalities (ischemia) were scored for each patient. Cardiac events were related to clinical and ECG data and DSE results. Four hundred twenty-eight cardiac events occurred in 366, documented cardiac death in 108 (total death, 247), nonfatal infarction in 128, and late revascularization in 192 patients. In a multivariable Cox proportional-hazards model, the ratio of documented cardiac death or (re)infarction was increased in the presence of stress-induced ischemia (hazard ratio, 3.3; 95% CI, 2.4 to 4.4) and extensive rest wall motion abnormalities (hazard ratio, 1.9; 95% CI, 1.3 to 2.6). The number of ischemic segments was predictive for late cardiac events. A normal DSE carried a relatively good prognosis, with an annual event rate of cardiac death or infarction of 1.3% over a 5-year period. CONCLUSIONS: In a large group of patients, DSE has an added value for predicting late cardiac events during long-term follow-up, improving the separation between high- risk and very-low-risk patients. PMID- 9989961 TI - Noninvasive diagnosis of ischemia-induced wall motion abnormalities with the use of high-dose dobutamine stress MRI: comparison with dobutamine stress echocardiography. AB - BACKGROUND: The analysis of wall motion abnormalities with dobutamine stress echocardiography (DSE) is an established method for the detection of myocardial ischemia. With ultrafast magnetic resonance tomography, identical stress protocols as used for echocardiography can be applied. METHODS AND RESULTS: In 208 consecutive patients (147 men, 61 women) with suspected coronary artery disease, DSE with harmonic imaging and dobutamine stress magnetic resonance (DSMR) (1.5 T) were performed before cardiac catheterization. DSMR images were acquired during short breath-holds in 3 short-axis views and a 4- and a 2-chamber view (gradient echo technique). Patients were examined at rest and during a standard dobutamine-atropine scheme until submaximal heart rate was reached. Regional wall motion was assessed in a 16-segment model. Significant coronary heart disease was defined as >/=50% diameter stenosis. Eighteen patients could not be examined by DSMR (claustrophobia 11 and adipositas 6) and 18 patients by DSE (poor image quality). Four patients did not reach target heart rate. In 107 patients, coronary artery disease was found. With DSMR, sensitivity was increased from 74.3% to 86.2% and specificity from 69.8% to 85.7% (both P<0.05) compared with DSE. Analysis for women yielded similar results. CONCLUSIONS: High-dose dobutamine magnetic resonance tomography can be performed with a standard dobutamine/atropine stress protocol. Detection of wall motion abnormalities by DSMR yields a significantly higher diagnostic accuracy in comparison to DSE. PMID- 9989962 TI - New noninvasive method for coronary flow reserve assessment: contrast-enhanced transthoracic second harmonic echo Doppler. AB - BACKGROUND: We tested the hypothesis that blood flow velocity could be recorded in the left anterior descending coronary artery (LAD) during transthoracic echocardiography by use of second harmonic echo Doppler modality along with contrast enhancement (intravenous Levovist) at rest and after pharmacologically induced maximal vasodilation to assess coronary flow reserve (CFR) with a totally noninvasive approach. METHODS AND RESULTS: Fifty-six consecutive patients undergoing coronary angiography underwent transthoracic contrast-enhanced pulsed wave Doppler recording of blood flow velocity in the LAD by use of harmonic color Doppler as a guide at rest and after maximal vasodilation by dipyridamole infusion. Contrast enhancement with the harmonic mode greatly improved the success rate of recording adequate pulsed-wave Doppler signal in the LAD. CFR was (mean+/-SD) 1.54+/-0.7 in patients with (group 1) and 2. 79+/-0.9 in patients without (group 2) significant LAD stenosis (lumen narrowing >70%) (P<0.001); sensitivity and specificity in detecting significant LAD stenosis were 86% and 90%, respectively. There was close agreement between CFRs determined by this new method and intracoronary Doppler flow wire. CONCLUSIONS: Contrast-enhanced transthoracic echo Doppler with the harmonic mode is a feasible and promising technique for assessing CFR in a totally noninvasive way. PMID- 9989963 TI - Mediterranean diet, traditional risk factors, and the rate of cardiovascular complications after myocardial infarction: final report of the Lyon Diet Heart Study. AB - BACKGROUND: The Lyon Diet Heart Study is a randomized secondary prevention trial aimed at testing whether a Mediterranean-type diet may reduce the rate of recurrence after a first myocardial infarction. An intermediate analysis showed a striking protective effect after 27 months of follow-up. This report presents results of an extended follow-up (with a mean of 46 months per patient) and deals with the relationships of dietary patterns and traditional risk factors with recurrence. METHODS AND RESULTS: Three composite outcomes (COs) combining either cardiac death and nonfatal myocardial infarction (CO 1), or the preceding plus major secondary end points (unstable angina, stroke, heart failure, pulmonary or peripheral embolism) (CO 2), or the preceding plus minor events requiring hospital admission (CO 3) were studied. In the Mediterranean diet group, CO 1 was reduced (14 events versus 44 in the prudent Western-type diet group, P=0.0001), as were CO 2 (27 events versus 90, P=0.0001) and CO 3 (95 events versus 180, P=0. 0002). Adjusted risk ratios ranged from 0.28 to 0.53. Among the traditional risk factors, total cholesterol (1 mmol/L being associated with an increased risk of 18% to 28%), systolic blood pressure (1 mm Hg being associated with an increased risk of 1% to 2%), leukocyte count (adjusted risk ratios ranging from 1.64 to 2.86 with count >9x10(9)/L), female sex (adjusted risk ratios, 0.27 to 0. 46), and aspirin use (adjusted risk ratios, 0.59 to 0.82) were each significantly and independently associated with recurrence. CONCLUSIONS: The protective effect of the Mediterranean dietary pattern was maintained up to 4 years after the first infarction, confirming previous intermediate analyses. Major traditional risk factors, such as high blood cholesterol and blood pressure, were shown to be independent and joint predictors of recurrence, indicating that the Mediterranean dietary pattern did not alter, at least qualitatively, the usual relationships between major risk factors and recurrence. Thus, a comprehensive strategy to decrease cardiovascular morbidity and mortality should include primarily a cardioprotective diet. It should be associated with other (pharmacological?) means aimed at reducing modifiable risk factors. Further trials combining the 2 approaches are warranted. PMID- 9989964 TI - Neurohumoral prediction of benefit from carvedilol in ischemic left ventricular dysfunction. Australia-New Zealand Heart Failure Group. AB - BACKGROUND: Plasma neurohormones were analyzed for prediction of adverse outcomes and response to treatment in 415 patients with ischemic left ventricular dysfunction randomly assigned to receive carvedilol or placebo. METHODS AND RESULTS: Atrial natriuretic peptide, brain natriuretic peptide (BNP), or norepinephrine (NE) levels above the group median were associated with increased mortality rates and heart failure. On multivariate analysis, both BNP and NE interacted with treatment to predict death or heart failure independent of age, New York Heart Association class, and left ventricular ejection fraction. For placebo, supramedian levels of BNP were associated with 3-fold the mortality rate of inframedian levels (20/104; 19% vs 6/99; 6%; P<0.01). For carvedilol, mortality rate was comparable in these 2 subgroups (12/109; 11% vs 8/94; 9%; NS). Corresponding rates for heart failure were 29/104 (28%) versus 3/99 (3%; P<0.001) for placebo and 16/109 (15%) versus 7/94 (7%; NS) for carvedilol. High NE levels did not predict additional benefit from carvedilol, which significantly reduced heart failure admissions only in those with NE levels below the median (13.1% to 4. 0%; P<0.01). In the 23% of the study population with supramedian BNP but inframedian levels of NE, carvedilol reduced hospital admission with heart failure by >90% (P<0.001). CONCLUSIONS: Carvedilol reduced mortality rates and heart failure in those with higher pretreatment BNP levels but lesser activation of plasma NE. Neurohumoral profiling may guide introduction of beta-blockade in heart failure. PMID- 9989965 TI - Percutaneous mechanical mitral commissurotomy with a newly designed metallic valvulotome: immediate results of the initial experience in 153 patients. AB - BACKGROUND: Percutaneous balloon valvotomy has become a common treatment of mitral stenosis, but the cost of the procedure remains a limitation in countries with restricted financial resources, leading to a frequent reuse of the disposable catheters. To overcome this limitation, a reusable metallic valvotomy device has been developed with the goals of both improving the mitral valvotomy results and decreasing the cost of the procedure. METHODS AND RESULTS: The device consists of a detachable metallic cylinder with 2 articulated bars screwed onto the distal end of a disposable catheter whose proximal end is connected to an activating pliers. By the transseptal route, the device is advanced across the valve over a traction guidewire. Squeezing the pliers opens the bars up to a maximum extent of 40 mm. The clinical experience consisted of 153 patients with a broad spectrum of mitral valve deformities. The procedure was successful in 92% of cases and resulted in a significant increase in mitral valve area, from 0.95+/ 0.2 to 2. 16+/-0.4 cm2. No increase in mitral regurgitation was noted in 80% of cases. Bilateral splitting of the commissures was observed in 87%. Complications were 2 cases of severe mitral regurgitation (1 requiring surgery), 1 pericardial tamponade, and 1 transient cerebrovascular embolic event. In this series, the maximum number of consecutive patients treated with the same device was 35. CONCLUSIONS: The results obtained with this new device are encouraging and at least comparable to those of current balloon techniques. Multiple uses after sterilization should markedly decrease the procedural cost, a major advantage in countries with limited resources and high incidence of mitral stenosis. PMID- 9989966 TI - Development of the cardiac conduction tissue in human embryos using HNK-1 antigen expression: possible relevance for understanding of abnormal atrial automaticity. AB - BACKGROUND: Abnormal atrial automaticity in young patients with structurally normal hearts is often located around the pulmonary veins and in sinus venosus related parts of the right atrium. We hypothesize that these ectopic pacemaker sites correspond to areas of embryonic myocardium with an early phenotypic differentiation, as indicated by differences in antigen expression during normal cardiac development. METHODS AND RESULTS: In human embryos ranging in age from 42 to 54 days of gestation, the development of the cardiac conduction system was studied with the use of HNK-1 immunohistochemistry. HNK-1 stains the developing atrioventricular conduction system, ie, the bundle branches, His bundle, right atrioventricular ring, and retroaortic ring. In addition, the myocardium around the common pulmonary vein showed transient HNK-1 antigen expression. In the right atrium, 3 HNK-1-positive connections were demonstrated between the sinoatrial node and the right atrioventricular ring. An anterior tract through the septum spurium connects the sinoatrial node with the anterior right atrioventricular ring, and 2 posterior tracts connect the sinoatrial node with the posterior right atrioventricular ring through the right venous valve (future crista terminalis) and sinus septum, encircling the coronary sinus. The medioposterior part of the right atrioventricular ring connected to the His bundle and the medioanterior part form 2 node-like structures. CONCLUSIONS: In patients with abnormal atrial automaticity, the distribution of left and right atrial pacemaker foci correspond to areas of the embryonic myocardium that temporarily express the HNK-1 antigen. PMID- 9989967 TI - Skeletal muscle mitochondrial DNA injury in patients with unilateral peripheral arterial disease. AB - BACKGROUND: Patients with peripheral arterial disease (PAD) have exercise limitation due to claudication-limited pain and metabolic alterations in skeletal muscle. PAD is also associated with oxidative stress, which is a known cause of mitochondrial DNA (mtDNA) injury. The present study was designed to test the hypothesis that PAD is associated with mtDNA injury, as reflected by an increased frequency of a specific 4977-base pair (bp) mtDNA deletion mutation. METHODS AND RESULTS: The deletion frequency was quantified in gastrocnemius muscle of 8 patients with unilateral PAD and 10 age-matched control subjects with the use of polymerase chain reaction methodologies. Muscle from the hemodynamically unaffected (less affected) PAD limb showed an 8-fold increased deletion frequency and the hemodynamically affected (worse affected) PAD limb had a 17-fold increased deletion frequency compared with muscle from control subjects. The frequency of the 4977-bp deletion in the worse-affected limb was positively correlated with the age of the patients but not the claudication-limited exercise performance of the patients. Total mtDNA content, citrate synthase activity, and cytochrome c oxidase activity were not different in the muscle from the 3 limb populations. However, the ratio of citrate synthase to cytochrome c oxidase was higher in the worse- versus less-affected limbs of PAD patients. CONCLUSIONS: The present study demonstrates a large increase in the frequency of the mtDNA 4977-bp deletion in patients with PAD but in a distribution not limited to the hemodynamically affected limb. PMID- 9989968 TI - Myocardial protection conferred by electromagnetic fields. AB - BACKGROUND: It has been reported that electromagnetic (EM) fields induce stress proteins in vitro. These proteins have been shown to be important in recovery from ischemia/reperfusion. It was, therefore, hypothesized that EM fields could activate stress responses in vivo and protect myocardial tissue during anoxia. METHODS AND RESULTS: Chick embryos were exposed to 4-, 6-, 8-, and 10- microT and 60-Hz EM fields for 20 minutes followed by a 1-hour rest period before placement in an anoxic chamber. Embryos were reoxygenated when survival of controls dropped to <40%, and final observations were made 30 minutes later. Data from 80 experiments (>500 EM field-exposed embryos) indicated that EM field protection was extremely significant (P<0.0001). Survival rates were 39.6% in controls and 68.7% in field-exposed embryos. In a second set of experiments, embryos were exposed for 20 minutes to several pretreatments: (1) hyperthermia (43 degreesC), (2) 60-Hz, 8- microT EM fields, or (3) 60-Hz, 8- microT EM fields plus a random EM noise field (8 microT). Embryo survival was 37.7% (control), 57.6% (heated), 69% (60-Hz EM field only), and 41.5% (60-Hz EM field plus EM noise). To confirm that heating resulting from field exposures did not occur, thermocouples were placed into several eggs at the site of the embryo during exposure; no increase in temperature was noted. CONCLUSIONS: We conclude that athermal EM field exposures induce stress responses that protect chick embryo myocardium from anoxia damage. These results suggest that EM field exposures may be a useful, noninvasive means of minimizing myocardial damage during surgery, transplantation, or heart attack in humans. PMID- 9989969 TI - Cardioprotective effect of angiotensin-converting enzyme inhibition against hypoxia/reoxygenation injury in cultured rat cardiac myocytes. AB - BACKGROUND: Although ACE inhibitors can protect myocardium against ischemia/reperfusion injury, the mechanisms of this effect have not yet been characterized at the cellular level. The present study was designed to examine whether an ACE inhibitor, cilazaprilat, directly protects cardiac myocytes against hypoxia/reoxygenation (H/R) injury. METHODS AND RESULTS: Neonatal rat cardiac myocytes in primary culture were exposed to hypoxia for 5.5 hours and subsequently reoxygenated for 1 hour. Myocyte injury was determined by the release of creatine kinase (CK). Both cilazaprilat and bradykinin significantly inhibited CK release after H/R in a dose-dependent fashion and preserved myocyte ATP content during H/R, whereas CV-11974, an angiotensin II receptor antagonist, and angiotensin II did not. The protective effect of cilazaprilat was significantly inhibited by Hoe 140 (a bradykinin B2 receptor antagonist), NG monomethyl-L-arginine monoacetate (L-NMMA) (an NO synthase inhibitor), and methylene blue (a soluble guanylate cyclase inhibitor) but not by staurosporine (a protein kinase C inhibitor), aminoguanidine (an inhibitor of inducible NO synthase), or indomethacin (a cyclooxygenase inhibitor). Cilazaprilat significantly enhanced bradykinin production in the culture media of myocytes after 5.5 hours of hypoxia but not in that of nonmyocytes. In addition, cilazaprilat markedly enhanced the cGMP content in myocytes during hypoxia, and this augmentation in cGMP could be blunted by L-NMMA and methylene blue but not by aminoguanidine. CONCLUSIONS: The present study demonstrates that cilazaprilat can directly protect myocytes against H/R injury, primarily as a result of an accumulation of bradykinin and the attendant production of NO induced by constitutive NO synthase in hypoxic myocytes in an autocrine/paracrine fashion. NO modulates guanylate cyclase and cGMP synthesis in myocytes, which may contribute to the preservation of energy metabolism and cardioprotection against H/R injury. PMID- 9989970 TI - Inhibition of inositol(1,4,5)Trisphosphate generation by endothelin-1 during postischemic reperfusion: A novel antiarrhythmic mechanism. AB - BACKGROUND: Reperfusion of ischemic rat hearts in the presence of thrombin or norepinephrine but not endothelin-1 causes the generation of inositol 1,4,5 trisphosphate (Ins 1,4,5P3) and arrhythmias. The present study investigates the effect of endothelin-1 on these responses. METHODS AND RESULTS: Ins 1,4,5P3 generation was quantified by use of [3H] labeling and high-performance liquid chromatography as well as by mass analysis. Twenty minutes of global ischemia followed by 2 minutes of reperfusion increased [3H]Ins 1,4,5P3 from 2828+/-265 to 5033+/-650 cpm/g tissue in the presence of thrombin 2.5 IU/mL and to 4561+/-286 cpm/g tissue in response to release of norepinephrine (n=4, P<0.01) in both cases. Reperfusion in the presence of endothelin-1 alone caused no change in Ins 1,4,5P3 (2762+/-240 cpm/g tissue), but when added together with thrombin or norepinephrine, endothelin-1 reduced the Ins 1,4,5P3 responses to 2313+/-197 and 1764+/-168 cpm/g tissue, respectively (n=4, P<0.01 in both cases). Similar inhibitory interactions between endothelin-1 10 nmol/L and thrombin 2.5 IU/mL were observed under normoxic conditions in nonperfused ventricle, eliminating the possibility that excessive vasoconstriction was responsible. In parallel studies, endothelin-1 suppressed the development of reperfusion arrhythmias initiated by either thrombin (ventricular fibrillation, 75% to 39%, n=16 to 18) or norepinephrine (83% to 8%, n=12 to 22) (P<0.01 in both cases). CONCLUSIONS: Inhibition of Ins 1,4,5P3 generation during myocardial reperfusion by endothelin 1 represents a novel antiarrhythmic mechanism. PMID- 9989971 TI - Validation of a new noncontact catheter system for electroanatomic mapping of left ventricular endocardium. AB - BACKGROUND: Improvements in cardiac mapping are required to advance our understanding and treatment of arrhythmias. This study validated a new noncontact multielectrode array catheter and accompanying analysis system to provide electroanatomic mapping of the entire left ventricular (LV) endocardium during a single beat. METHODS AND RESULTS: A 9F 64-electrode balloon array catheter with an inflated size of 1.8x4.6 cm was used to simultaneously record electrical potentials generated by the heart and locate a standard electrophysiology (EP) catheter within the same chamber. By use of the recorded location of the EP catheter tip, LV geometry was determined. Array potentials served as inputs to a high-order boundary-element method to produce 3360 potential points on the endocardial surface translatable into electrograms or color-coded activation maps. Three methods of validation were used: (1) driven electrodes in an in vitro tank were located; (2) waveforms generated from the array catheter were compared with catheter contact waveforms in canine LV; and (3) sites of local LV endocardial activation were located and marked with radiofrequency lesions. Tank testing located a driven electrode to within 2.33+/-0.44 mm. Correlation of timing and morphology of computed versus contact electrograms was 0.966. Radiofrequency lesions marked 17 endocardial pacing sites to within 4.0+/-3.2 mm. CONCLUSIONS: This new system provides anatomically accurate endocardial isopotential mapping during a single cardiac cycle. The locator component enabled placement of a separate EP catheter to any site within the mapped chamber. PMID- 9989972 TI - Attenuated acute cardiac rejection in NOS2 -/- recipients correlates with reduced apoptosis. AB - BACKGROUND: The mechanisms through which NOS2-mediated pathways regulate graft failure in acute cardiac rejection are ill defined. To determine whether apoptosis promoted by NOS2 may contribute, we used a heterotopic transplant model to study mouse cardiac allografts placed in recipients with targeted gene deletion of NOS2. METHODS AND RESULTS: Using 5 different indexes of apoptosis, we showed that mouse cardiac allografts placed in NOS2 -/- recipients (n=7) had reduced apoptotic activity compared with those in NOS2 +/+ controls (n=8). There were significantly fewer TUNEL-positive nuclei per high-powered field (P<0.01), less DNA fragmentation (antinucleosome ELISA; P<0.05), lower corrected transcript levels for caspase-1 and -3 (32P reverse transcriptase-polymerase chain reaction; P<0.01), and reduced caspase-3 activity (cleavage of DEVD-pNA [P<0.001] and poly [ADP-ribose] polymerase) in grafts from NOS2 -/- recipients. This concordant reduction in apoptotic indexes paralleled the improved histological outcome of grafts transplanted into NOS2 -/- recipients (assessed as rejection scores; P=0.012). To identify pathways controlled by NOS2, we compared intragraft transcript levels of potential triggers and regulators. Whereas Fas ligand/Fas and tumor necrosis factor (TNF)-alpha/TNF receptor-1 levels were not altered by NOS2 deficiency, transcript levels for p53 were significantly lower in grafts from NOS2 -/- recipients, coinciding with a significant increase in the antiapoptotic Bcl-2/Bax balance and decrease in Bcl-Xl levels. CONCLUSIONS: Using NOS2 knockout mice, we demonstrated that NOS2-mediated pathways can promote acute rejection, at least in part, by inducing apoptotic cell death. When NOS2 is present, p53 might control NOS2-mediated apoptosis by stimulating Bax and repressing Bcl-2 and Bcl-Xl expression, which may activate the cell death program in the rejecting heart. PMID- 9989973 TI - Images in cardiovascular medicine. Sewing needle transfixing the posterior wall of the left ventricle causes death. PMID- 9989974 TI - Toll, a new piece in the puzzle of innate immunity. PMID- 9989975 TI - Mobilizing dendritic cells for tolerance, priming, and chronic inflammation. PMID- 9989976 TI - Endotoxin-tolerant mice have mutations in Toll-like receptor 4 (Tlr4) AB - Bacterial lipopolysaccharide (LPS) provokes a vigorous, generalized proinflammatory state in the infected host. Genetic regulation of this response has been localized to the Lps locus on mouse chromosome 4, through study of the C3H/HeJ and C57BL/10ScCr inbred strains. Both C3H/HeJ and C57BL/10ScCr mice are homozygous for a mutant Lps allele (Lpsd/d) that confers hyporesponsiveness to LPS challenge, and therefore exhibit natural tolerance to its lethal effects. Genetic and physical mapping of 1,345 backcross progeny segregating this mutant phenotype confined Lps to a 0.9-cM interval spanning 1.7 Mb. Three transcription units were identified within the candidate interval, including Toll-like receptor 4 (Tlr4), part of a protein family with members that have been implicated in LPS induced cell signaling. C3H/HeJ mice have a point mutation within the coding region of the Tlr4 gene, resulting in a nonconservative substitution of a highly conserved proline by histidine at codon 712, whereas C57BL/ 10ScCr mice exhibit a deletion of Tlr4. Identification of distinct mutations involving the same gene at the Lps locus in two different hyporesponsive inbred mouse strains strongly supports the hypothesis that altered Tlr4 function is responsible for endotoxin tolerance. PMID- 9989977 TI - Interaction of dendritic cells with skin endothelium: A new perspective on immunosurveillance. AB - The goal of this study was to determine the mechanisms by which dendritic cells (DCs) in blood could interact with endothelium, a prerequisite to extravasation into tissues. Our results indicate that DCs express both HECA-452-reactive and nonreactive isoforms of P-selectin glycoprotein ligand 1 (PSGL-1) and can tether and roll efficiently on E- and P-selectin under flow conditions in vitro. Freshly isolated blood DCs were further observed to roll continuously along noninflamed murine dermal endothelium in vivo. This interaction is strictly dependent on endothelial selectins, as shown by experiments with blocking antibodies and with E- and P-selectin-deficient mice. We hypothesize that DCs in blood are constitutively poised at the interface of blood and skin, ready to extravasate upon induction of inflammation, and we showed that cutaneous inflammation results in a rapid recruitment of DCs from the blood to tissues. We propose that this is an important and previously unappreciated element of immunosurveillance. PMID- 9989979 TI - Treponema pallidum major sheath protein homologue Tpr K is a target of opsonic antibody and the protective immune response. AB - We have identified a family of genes that code for targets for opsonic antibody and protective immunity in T. pallidum subspecies pallidum using two different approaches, subtraction hybridization and differential immunologic screening of a T. pallidum genomic library. Both approaches led to the identification of a polymorphic multicopy gene family with predicted amino acid homology to the major sheath protein of Treponema denticola. One of the members of this gene family, tpr K, codes for a protein that is predicted to have a cleavable signal peptide and be located in the outer membrane of the bacterium. Reverse transcription polymerase chain reaction analysis of T. pallidum reveals that Tpr K is preferentially transcribed in the Nichols strain of T. pallidum. Antibodies directed to purified recombinant variable domain of Tpr K can opsonize T. pallidum, Nichols strain, for phagocytosis, supporting the hypothesis that this portion of the protein is exposed at the surface of the treponeme. Immunization of rabbits with the purified recombinant variable domain of Tpr K provides significant protection against infection with the Nichols strain of T. pallidum. This gene family is hypothesized to be central to pathogenesis and immunity during syphilis infection. PMID- 9989978 TI - Neonatal idiotypic exposure alters subsequent cytokine, pathology, and survival patterns in experimental Schistosoma mansoni infections. AB - Exposure to maternal idiotypes (Ids) or antigens might predispose a child to develop an immunoregulated, asymptomatic clinical presentation of schistosomiasis. We have used an experimental murine system to address the role of Ids in this immunoregulation. Sera from mice with 8-wk Schistosoma mansoni infection, chronic (20-wk infection) moderate splenomegaly syndrome (MSS), or chronic hypersplenomegaly syndrome (HSS) were passed over an S. mansoni soluble egg antigen (SEA) immunoaffinity column to prepare Ids (8WkId, MSS Id, HSS Id). Newborn mice were injected with 8WkId, MSS Id, HSS Id, or normal mouse immunoglobulin (NoMoIgG) and infected with S. mansoni 8 wk later. Mice exposed to 8WkId or MSS Id as newborns had prolonged survival and decreased morbidity compared with mice that received HSS Id or NoMoIgG. When stimulated with SEA, 8WkId, or MSS Id, spleen cells from mice neonatally injected with 8WkId or MSS Id produced more interferon gamma than spleen cells from mice neonatally injected with HSS Id or NoMoIgG. Furthermore, neonatal exposure to 8WkId or MSS Id, but not NoMoIgG or HSS Id, led to significantly smaller granuloma size and lower hepatic fibrosis levels in infected mice. Together, these results indicate that perinatal exposure to appropriate anti-SEA Ids induces long-term effects on survival, pathology, and immune response patterns in mice subsequently infected with S. mansoni. PMID- 9989980 TI - Impaired antibacterial host defense in mice lacking the N-formylpeptide receptor. AB - N-formylpeptides derive from bacterial and mitochondrial proteins, and bind to specific receptors on mammalian phagocytes. Since binding induces chemotaxis and activation of phagocytes in vitro, it has been postulated that N-formylpeptide receptor signaling in vivo may be important in antimicrobial host defense, although direct proof has been lacking. Here we test this hypothesis in mice lacking the high affinity N-formylpeptide receptor (FPR), created by targeted gene disruption. FPR-/- mice developed normally, but had increased susceptibility to challenge with Listeria monocytogenes, as measured by increased mortality compared with wild-type littermates. FPR-/- mice also had increased bacterial load in spleen and liver 2 d after infection, which is before development of a specific cellular immune response, suggesting a defect in innate immunity. Consistent with this, neutrophil chemotaxis in vitro and neutrophil mobilization into peripheral blood in vivo in response to the prototype N-formylpeptide fMLF (formyl-methionyl-leucyl-phenylalanine) were both absent in FPR-/- mice. These results indicate that FPR functions in antibacterial host defense in vivo. PMID- 9989981 TI - Interferons regulate the phenotype of wild-type and mutant herpes simplex viruses in vivo. AB - Mechanisms responsible for neuroattenuation of herpes simplex virus (HSV) have been defined previously by studies of mutant viruses in cultured cells. The hypothesis that null mutations in host genes can override the attenuated phenotype of null mutations in certain viral genes was tested. Mutants such as those in infected cell protein (ICP) 0, thymidine kinase, ribonucleotide reductase, virion host shutoff, and ICP34.5 are reduced in their capacity to replicate in nondividing cells in culture and in vivo. The replication of these viruses was examined in eyes and trigeminal ganglia for 1-7 d after corneal inoculation in mice with null mutations (-/-) in interferon receptors (IFNR) for type I IFNs (IFN-alpha/betaR), type II IFN (IFN-gammaR), and both type I and type II IFNs (IFN-alpha/beta/gammaR). Viral titers in eyes and ganglia of IFN-gammaR-/ mice were not significantly different from congenic controls. However, in IFN alpha/betaR-/- or IFN-alpha/beta/gammaR-/- mice, growth of all mutants, including those with significantly impaired growth in cell culture, was enhanced by up to 1,000-fold in eyes and trigeminal ganglia. Blepharitis and clinical signs of infection were evident in IFN-alpha/betaR-/- and IFN-alpha/beta/gammaR-/- but not control mice for all viruses. Also, IFNs were shown to significantly reduce productive infection of, and spread from intact, but not scarified, corneas. Particularly striking was restoration of near-normal trigeminal ganglion replication and neurovirulence of an ICP34.5 mutant in IFN-alpha/betaR-/- mice. These data show that IFNs play a major role in limiting mutant and wild-type HSV replication in the cornea and in the nervous system. In addition, the in vivo target of ICP34.5 may be host IFN responses. These experiments demonstrate an unsuspected role for host factors in defining the phenotypes of some HSV mutants in vivo. The phenotypes of mutant viruses therefore cannot be interpreted based solely upon studies in cell culture but must be considered carefully in the context of host factors that may define the in vivo phenotype. PMID- 9989982 TI - Augmentation of antigen receptor-mediated responses by histamine H1 receptor signaling. AB - Histamine is considered one of the important mediators of immediate hypersensitivity and inflammation, and acts via G protein-coupled receptors. Here, we report that histamine may affect antigen receptor-mediated immune responses of T and B cells via a signal(s) from histamine H1 receptors (H1Rs). Histamine exhibited enhancing effects on the in vitro proliferative responses of anti-CD3epsilon- or anti-IgM-stimulated spleen T and B cells, respectively, at the culture condition that the fetal calf serum was dialyzed before culture and c kit-positive cells were depleted from the spleen cells. In studies of histamine H1R knockout mice, H1R-deficient T cells had low proliferative responses to anti CD3epsilon cross-linking or antigen stimulation in vitro. B cells from H1R deficient mice were also affected, demonstrating low proliferative responses to B cell receptor cross-linking. Antibody production against trinitrophenyl-Ficoll was reduced in H1R-deficient mice. Other aspects of T and B cell function were normal in the H1R knockout mice. H1R-deficient T and B cells showed normal responses upon stimulation with interleukin (IL)-2, IL-4, CD40 ligand, CD40 ligand plus IL-4, and lipopolysaccharide. Collectively, these results imply that the signal generated by histamine through H1R augments antigen receptor-mediated immune responses, suggesting cross-talk between G protein-coupled receptors and antigen receptor-mediated signaling. PMID- 9989984 TI - CD34(+) hematopoietic stem cells exert accessory function in lipopolysaccharide induced T cell stimulation and CD80 expression on monocytes. AB - CD34(+) hematopoietic stem cells, which circulate in peripheral blood with very low frequency, exert essential accessory function during lipopolysaccharide (LPS) induced human T lymphocyte activation, resulting in interferon gamma production and proliferation. In contrast, stimulation of T cells by "conventional" recall antigens is not controlled by blood stem cells. These conclusions are based on the observation that depletion of CD34(+) blood stem cells results in a loss of LPS-induced T cell stimulation as well as reduced expression of CD80 antigen on monocytes. The addition of CD34-enriched blood stem cells resulted in a recovery of reactivity of T cells and monocytes to LPS. Blood stem cells could be replaced by the hematopoietic stem cell line KG-1a. These findings may be of relevance for high risk patients treated with stem cells or stem cell recruiting compounds and for patients suffering from endotoxin-mediated diseases. PMID- 9989983 TI - Sustained receptor activation and hyperproliferation in response to granulocyte colony-stimulating factor (G-CSF) in mice with a severe congenital neutropenia/acute myeloid leukemia-derived mutation in the G-CSF receptor gene. AB - In approximately 20% of cases of severe congenital neutropenia (SCN), mutations are found in the gene encoding the granulocyte colony-stimulating factor receptor (G-CSF-R). These mutations introduce premature stop codons, which result in truncation of 82-98 COOH-terminal amino acids of the receptor. SCN patients who develop secondary myelodysplastic syndrome and acute myeloid leukemia almost invariably acquired a GCSFR mutation, suggesting that this genetic alteration represents a key step in leukemogenesis. Here we show that an equivalent mutation targeted in mice (gcsfr-Delta715) results in the selective expansion of the G-CSF responsive progenitor (G-CFC) compartment in the bone marrow. In addition, in vivo treatment of gcsfr-Delta715 mice with G-CSF results in increased production of neutrophils leading to a sustained neutrophilia. This hyperproliferative response to G-CSF is accompanied by prolonged activation of signal transducer and activator of transcription (STAT) complexes and extended cell surface expression of mutant receptors due to defective internalization. In view of the continuous G CSF treatment of SCN patients, these data provide insight into why progenitor cells expressing truncated receptors clonally expand in vivo, and why these cells may be targets for additional genetic events leading to leukemia. PMID- 9989985 TI - T cell affinity maturation by selective expansion during infection. AB - T lymphocyte recognition of infected cells is mediated by T cell receptors (TCRs) interacting with their ligands, self-major histocompatibility complex (MHC) molecules complexed with pathogen-derived peptides. Serial TCR interactions with potentially small numbers of MHC/ peptide complexes on infected cells transmit signals that result in T lymphocyte expansion and activation of effector functions. The impact of TCR affinity for MHC/peptide complexes on the rate or extent of in vivo T cell expansion is not known. Here we show that in vivo expansion of complex T cell populations after bacterial infection is accompanied by an increase in their overall affinity for antigen. T cell populations that have undergone additional rounds of in vivo expansion express a narrower range of TCRs, have increased sensitivity for antigen in cytotoxic T lymphocyte assays, and bind MHC/peptide complexes with greater affinity. The selective expansion of higher affinity T cells provides an in vivo mechanism for optimizing the early detection of infected cells. PMID- 9989986 TI - 312-nanometer ultraviolet B light (narrow-band UVB) induces apoptosis of T cells within psoriatic lesions. AB - Narrow-band (312 nm) ultraviolet B light (UVB) is a new form of therapy for psoriasis, but its mechanism of action is unknown. In a bilateral comparison clinical study, daily exposure of psoriatic plaques to broad-band UVB (290-320 nm) or 312-nm UVB depleted T cells from the epidermis and dermis of psoriatic lesions. However, 312-nm UVB was significantly more depleting in both tissue compartments. To characterize the mechanism of T cell depletion, assays for T cell apoptosis were performed on T cells derived from UVB-irradiated skin in vivo and on T cells irradiated in vitro with 312-nm UVB. Apoptosis was induced in T cells exposed to 50-100 mJ/cm2 of 312-nm UVB in vitro, as measured by increased binding of fluorescein isothiocyanate (FITC)-Annexin V to CD3(+) cells and by characteristic cell size/granularity changes measured by cytometry. In vivo exposure of psoriatic skin lesions to 312-nm UVB for 1-2 wk also induced apoptosis in T cells as assessed by the terminal deoxynucleotidyl transferase mediated dUTP-biotin nick end labeling (TUNEL) reaction in tissue sections, by binding of FITC-Annexin V to CD3(+) T cells contained in epidermal cell suspensions, and by detection of apoptosis-related size shifts of CD3(+) cells. Induction of T cell apoptosis could be the main mechanism by which 312-nm UVB resolves psoriasis skin lesions. PMID- 9989988 TI - Cells capable of bone production engraft from whole bone marrow transplants in nonablated mice. AB - Allogeneic and autologous marrow transplants are routinely used to correct a wide variety of diseases. In addition, autologous marrow transplants potentially provide opportune means of delivering genes in transfected, engrafting stem cells. However, relatively little is known about the mechanisms of engraftment in transplant recipients, especially in the nonablated setting and with regard to cells not of hemopoietic origin. In particular, this includes stromal cells and progenitors of the osteoblastic lineage. We have demonstrated for the first time that a whole bone marrow transplant contains cells that engraft and become competent osteoblasts capable of producing bone matrix. This was done at the individual cell level in situ, with significant numbers of donor cells being detected by fluorescence in situ hybridization in whole femoral sections. Engrafted cells were functionally active as osteoblasts producing bone before being encapsulated within the bone lacunae and terminally differentiating into osteocytes. Transplanted cells were also detected as flattened bone lining cells on the periosteal bone surface. PMID- 9989987 TI - The transcription factor interferon regulatory factor 1 is expressed after cerebral ischemia and contributes to ischemic brain injury. AB - The transcription factor interferon regulatory factor 1 (IRF-1) is involved in the molecular mechanisms of inflammation and apoptosis, processes that contribute to ischemic brain injury. In this study, the induction of IRF-1 in response to cerebral ischemia and its role in ischemic brain injury were investigated. IRF-1 gene expression was markedly upregulated within 12 h of occlusion of the middle cerebral artery in C57BL/6 mice. The expression reached a peak 4 d after ischemia (6.0 +/- 1.8-fold; P < 0.001) and was restricted to the ischemic regions of the brain. The volume of ischemic injury was reduced by 23 +/- 3% in IRF-1(+/-) and by 46 +/- 9% in IRF-1(-/-) mice (P < 0.05). The reduction in infarct volume was paralleled by a substantial attenuation in neurological deficits. Thus, IRF-1 is the first nuclear transacting factor demonstrated to contribute directly to cerebral ischemic damage and may be a novel therapeutic target in ischemic stroke. PMID- 9989989 TI - Commitment to the B lymphoid lineage occurs before DH-JH recombination. AB - Lineage commitment in B lymphopoiesis remains poorly understood due to the inability to clearly define newly committed B lineage progenitors and their multipotential descendants. We examined the potential of three recently described progenitor populations in adult mouse bone marrow to differentiate into each hematopoietic lineage. The earliest of these, termed fraction (Fr.) A0, exhibited myeloid, erythroid, and B and T lymphoid progenitor activity and included individual cells with myeloid/B lymphoid potential. In sharp contrast, two later populations, termed Frs. A1 and A2 and characterized by surface B220 expression and transcription of the germline immunoglobulin heavy chain (IgH) locus, lacked progenitor activity for all hematopoietic lineages except B lymphocytes. These observations, together with single cell polymerase chain reaction analysis showing a lack of DHJH rearrangements in each population and experiments showing identical precursor potentials when these populations were derived from recombination activating gene (Rag)-1(-/-) and JH-/- mice, demonstrate that commitment to the B lymphoid lineage occurs before and independently of VHDHJH recombination. PMID- 9989990 TI - Macrophage microbicidal mechanisms in vivo: reactive nitrogen versus oxygen intermediates in the killing of intracellular visceral Leishmania donovani. AB - To determine the relative contributions of respiratory burst-derived reactive oxygen intermediates (ROI) versus reactive nitrogen intermediates (RNI) to macrophage-mediated intracellular host defense, mice genetically deficient in these mechanisms were challenged with Leishmania donovani, a protozoan that selectively parasitizes visceral tissue macrophages. During the early stage of liver infection at wk 2, both respiratory burst-deficient gp91(phox)-/- (X-linked chronic granulomatous disease [X-CGD]) mice and inducible nitric oxide synthase (iNOS) knockout (KO) mice displayed comparably increased susceptibility. Thereafter, infection was unrestrained in mice lacking iNOS but was fully controlled in X-CGD mice. Mononuclear cell influx into infected liver foci in X CGD and iNOS KO mice was also overtly impaired at wk 2. However, granuloma assembly in parasitized tissue eventually developed in both hosts but with divergent effects: mature granulomas were functionally active (leishmanicidal) in X-CGD mice but inert in iNOS-deficient animals. These results suggest that (a) ROI and RNI probably act together in the early stage of intracellular infection to regulate both tissue recruitment of mononuclear inflammatory cells and the initial extent of microbial replication, (b) RNI alone are necessary and sufficient for eventual control of visceral infection, and (c) although mature granulomas have traditionally been associated with control of such infections, these structures fail to limit intracellular parasite replication in the absence of iNOS. PMID- 9989992 TI - An arrayable flow-through microcentrifuge for high-throughput instrumentation-a matter of scale. PMID- 9989991 TI - A human immunoglobulin (Ig)A calpha3 domain motif directs polymeric Ig receptor mediated secretion. AB - Polymeric immunoglobulins provide immunological protection at mucosal surfaces to which they are specifically transported by the polymeric immunoglobulin receptor (pIgR). Using a panel of human IgA1/IgG1 constant region "domain swap" mutants, the binding site for the pIgR on dimeric IgA (dIgA) was localized to the Calpha3 domain. Selection of random peptides for pIgR binding and comparison with the IgA sequence suggested amino acids 402-410 (QEPSQGTTT), in a predicted exposed loop of the Calpha3 domain, as a potential binding site. Alanine substitution of two groups of amino acids in this area abrogated the binding of dIgA to pIgR, whereas adjacent substitutions in a beta-strand immediately NH2-terminal to this loop had no effect. All pIgR binding IgA sequences contain a conserved three amino acid insertion, not present in IgG, at this position. These data localize the pIgR binding site on dimeric human IgA to this loop structure in the Calpha3 domain, which directs mucosal secretion of polymeric antibodies. We propose that it may be possible to use a pIgR binding motif to deliver antigen-specific dIgA and small-molecule drugs to mucosal epithelia for therapy. PMID- 9989993 TI - 1918 Spanish influenza: the secrets remain elusive. PMID- 9989994 TI - Malaria vaccines. PMID- 9989995 TI - Genetic isolates: separate but equal? PMID- 9989997 TI - Nitrogen fertilizer: retrospect and prospect. PMID- 9989998 TI - Accelerated chemical synthesis of peptides and small proteins. AB - The chemical synthesis of peptides and small proteins is a powerful complementary strategy to recombinant protein overexpression and is widely used in structural biology, immunology, protein engineering, and biomedical research. Despite considerable improvements in the fidelity of peptide chain assembly, side-chain protection, and postsynthesis analysis, a limiting factor in accessing polypeptides containing greater than 50 residues remains the time taken for chain assembly. The ultimate goal of this work is to establish highly efficient chemical procedures that achieve chain-assembly rates of approximately 10-15 residues per hour, thus underpinning the rapid chemical synthesis of long polypeptides and proteins, including cytokines, growth factors, protein domains, and small enzymes. Here we report Boc chemistry that employs O-(7-azabenzotriazol 1-yl)-N,N, N',N'-tetramethyluronium hexafluorophosphate (HATU)/dimethyl sulfoxide in situ neutralization as the coupling agent and incorporates a protected amino acid residue every 5 min to produce peptides of good quality. This rapid coupling chemistry was successfully demonstrated by synthesizing several small to medium peptides, including the "difficult" C-terminal sequence of HIV-1 proteinase (residues 81-99); fragment 65-74 of the acyl carrier protein; conotoxin PnIA(A10L), a potent neuronal nicotinic receptor antagonist; and the pro inflammatory chemotactic protein CP10, an 88-residue protein, by means of native chemical ligation. The benefits of this approach include enhanced ability to identify and characterize "difficult couplings," rapid access to peptides for biological and structure-activity studies, and accelerated synthesis of tailored large peptide segments (<50 residues) for use in chemoselective ligation methods. PMID- 9989999 TI - Femtosecond dynamics of the DNA intercalator ethidium and electron transfer with mononucleotides in water. AB - Ethidium (E) is a powerful probe of DNA dynamics and DNA-mediated electron transfer (ET). Molecular dynamical processes, such as solvation and orientation, are important on the time scale of ET. Here, we report studies of the femtosecond and picosecond time-resolved dynamics of E, E with 2'deoxyguanosine triphosphate (GTP) in water, and E with 7-deaza-2'-deoxyguanosine triphosphate (ZTP) in water; E undergoes ET with ZTP but not GTP. These studies elucidate the critical role of relative orientational motions of the donor-acceptor complex on ET processes in solution. For ET from ZTP to E, such motions are in fact the rate-determining step. Our results indicate that these complexes reorient before ET. The time scale for the solvation of E in water is 1 ps, and the orientational relaxation time of E is 70 ps. The impact of orientational and solvation effects on ET between E and mononucleotides must be considered in the application of E as a probe of DNA ET. PMID- 9990001 TI - Volatile buffers can override the "pH memory" of subtilisin catalysis in organic media. AB - The protonation state and activity of enzymes in low-water media are affected by the aqueous pH before drying ("pH memory"). However, both protonation and activity will change if buffer ions can be removed as volatile or organic extractable weak acids or bases. With NH4OOCH buffers, in which both ions can be removed, pH memory disappears completely for subtilisin-catalyzed transesterification in hexane. Only weak pH memory is found with buffers having one volatile component, NH4-phosphate and NaOOCH. The changes in ionization state result from proton exchanges like Protein-COO-NH4+ --> Protein-COOH + NH3 (g) and Protein-NH3+HCOO- --> Protein-NH2 + HOOCH (g). An equivalent, complementary picture is that net charges on the protein and buffer ions must remain equal and opposite. With NaOOCH buffers, loss of some HCOO- ions gives a more negative net charge on the protein, balanced by the excess Na+. With NH4-phosphate buffers, loss of NH3 gives protein with a more positive net charge. The resulting catalytic activities were high and low, respectively, similar to those after drying from Na-phosphate buffers of optimal (8.5) and acid pH. All of the above effects have been demonstrated for both covalently immobilized subtilisin and the lyophilized free enzyme. Subtilisin lyophilized from NH4OOCH buffers gave pH approximately 4 after redissolution in water, probably because removal of HCOO- counterions remains incomplete. The resulting catalytic activity was low. The effects are discussed in relation to the possible locations, in low-dielectric media, of the positive charge that balances the net negative catalytic triad in active subtilisin. PMID- 9990000 TI - Brominated 7-hydroxycoumarin-4-ylmethyls: photolabile protecting groups with biologically useful cross-sections for two photon photolysis. AB - Photochemical release (uncaging) of bioactive messengers with three-dimensional spatial resolution in light-scattering media would be greatly facilitated if the photolysis could be powered by pairs of IR photons rather than the customary single UV photons. The quadratic dependence on light intensity would confine the photolysis to the focus point of the laser, and the longer wavelengths would be much less affected by scattering. However, previous caged messengers have had very small cross sections for two-photon excitation in the IR region. We now show that brominated 7-hydroxycoumarin-4-ylmethyl esters and carbamates efficiently release carboxylates and amines on photolysis, with one- and two-photon cross sections up to one or two orders of magnitude better than previously available. These advantages are demonstrated on neurons in brain slices from rat cortex and hippocampus excited by glutamate uncaged from N-(6-bromo-7-hydroxycoumarin-4 ylmethoxycarbonyl)-L-glutamate (Bhc-glu). Conventional UV photolysis of Bhc-glu requires less than one-fifth the intensities needed by one of the best previous caged glutamates, gamma-(alpha-carboxy-2-nitrobenzyl)-L-glutamate (CNB-glu). Two photon photolysis with raster-scanned femtosecond IR pulses gives the first three dimensionally resolved maps of the glutamate sensitivity of neurons in intact slices. Bhc-glu and analogs should allow more efficient and three-dimensionally localized uncaging and photocleavage, not only in cell biology and neurobiology but also in many technological applications. PMID- 9990002 TI - Separation of a midlevel density current from the bottom of a continental slope. AB - The high-salinity water flowing out of the Mediterranean Sea descends to mid depths in the density-stratified ocean, continues as a narrow jet along the Iberian continental slope, and intermittently detaches large-scale eddies (called "Meddies"). This process is important because it maintains the relatively high mean salinity of a major water mass (the "Mediterranean Intermediate Water") in the North Atlantic. Our simplified model of this jet consists of a moving layer with intermediate density rho2 sandwiched between motionless layers of density rho1 < rho2 and rho3 > rho2. The inshore (anticyclonic) portion of the midlevel jet (in the "rho2-water") rests on an inclined bottom (the continental slope), whereas the (cyclonic) offshore portion rests on the density interface of the stagnant deep (rho3) layer. An inviscid, steady, and finite-amplitude longwave theory is used to show that if the cross-stream topographic slope increases gradually in the downstream direction, then the "rho2-jet" is deflected off the bottom slope and onto the upper density interface of the rho3 layer. The computed magnitude of this separation effect is such as to produce an essentially free jet which is removed from the stabilizing influence of the continental topography. It is therefore conjectured that time-dependent effects (baroclinic instability) will produce further amplification, causing an eddy to detach seaward from the branch of the jet remaining on the slope. PMID- 9990003 TI - A plant virus-encoded protein facilitates long-distance movement of heterologous viral RNA. AB - Transport of plant viruses from cell to cell typically involves one or more viral proteins that supply specific cell-to-cell movement functions. Long-distance transport of viruses through the vascular system is a less well understood process with requirements different from those of cell-to-cell movement. Usually viral coat protein (CP) is required for long-distance movement, but groundnut rosette umbravirus (GRV) does not code for a CP. However, this virus moves efficiently from cell to cell and long distance. We demonstrate here that the protein encoded by ORF3 of GRV can functionally replace the CP of tobacco mosaic virus (TMV) for long-distance movement. In spite of low levels of virus RNA accumulation in infected cells, chimeric TMV with a replacement of the CP gene by GRV ORF3 was able to move rapidly through the phloem. Moreover, this chimeric virus complemented long-distance movement of another CP-deficient TMV derivative expressing the gene encoding the green fluorescent protein. Thus, the GRV ORF3 encoded protein represents a class of trans-acting long-distance movement factors that can facilitate trafficking of an unrelated viral RNA. PMID- 9990004 TI - Structure-activity analysis of synthetic autoinducing thiolactone peptides from Staphylococcus aureus responsible for virulence. AB - The synthesis of virulence factors and other extracellular proteins responsible for pathogenicity in Staphylococcus aureus is under the control of the agr locus. A secreted agr-encoded peptide, AgrD, processed from the AgrD gene product, is known to be an effector of self-strain activation and cross-strain inhibition of the agr response. Biochemical analysis of AgrD peptides isolated from culture supernatants has suggested that they contain an unusual thiol ester-linked cyclic structure. In the present work, chemical synthesis is used to confirm that the mature AgrD peptides contain a thiolactone structure and that this feature is absolutely necessary for full biological activity. The AgrD synthetic thiolactone peptides exhibited biological activity in vivo in a mouse protection test. Structure-activity studies have allowed key aspects of the peptide structure involved in the differential activation and inhibition functions to be identified. Accordingly, we propose a model for activation and inhibition of the agr response in which the former, but not the latter, involves specific acylation of the agr transmembrane receptor, AgrC. PMID- 9990005 TI - Receptor-induced polymerization of coatomer. AB - Coatomer, the coat protein complex of COPI vesicles, is involved in the budding of these vesicles, but the underlying mechanism is unknown. Toward a better understanding of this process, the interaction between coatomer and the cytoplasmic domain of a major transmembrane protein of COPI vesicles, p23, was studied. Interaction of coatomer with this peptide domain results in a conformational change and polymerization of the complex in vitro. This changed conformation also is observed in vivo, i.e., on the surface of authentic, isolated COPI vesicles. An average of four peptides was found associated with one coatomer complex after polymerization. Based on these results, we propose a mechanism by which the induced conformational change of coatomer results in its polymerization, and thus drives formation of the bud on the Golgi membrane during biogenesis of a COPI vesicle. PMID- 9990006 TI - Nuclear localization of the C1 factor (host cell factor) in sensory neurons correlates with reactivation of herpes simplex virus from latency. AB - After a primary infection, herpes simplex virus is maintained in a latent state in neurons of sensory ganglia until complex stimuli reactivate viral lytic replication. Although the mechanisms governing reactivation from the latent state remain unknown, the regulated expression of the viral immediate early genes represents a critical point in this process. These genes are controlled by transcription enhancer complexes whose assembly requires and is coordinated by the cellular C1 factor (host cell factor). In contrast to other tissues, the C1 factor is not detected in the nuclei of sensory neurons. Experimental conditions that induce the reactivation of herpes simplex virus in mouse model systems result in rapid nuclear localization of the protein, indicating that the C1 factor is sequestered in these cells until reactivation signals induce a redistribution of the protein. The regulated localization suggests that C1 is a critical switch determinant of the viral lytic-latent cycle. PMID- 9990007 TI - Two differently regulated nuclear factor kappaB activation pathways triggered by the cytoplasmic tail of CD40. AB - CD40 signaling modulates the immune response at least in part by activation of nuclear factor kappaB (NFkappaB). It has been shown that two distinct domains in the CD40 cytoplasmic tail (cyt), namely cyt-N and cyt-C, independently activate NFkappaB. Although four members of the tumor necrosis factor receptor-associated factor (TRAF) family, including TRAF2, TRAF3, TRAF5, and TRAF6, bind to the CD40 cyt, how each TRAF protein contributes to the NFkappaB activation by CD40 is not clear. Here we report that TRAF2, TRAF3, and TRAF5 bind cyt-C, whereas TRAF6 binds cyt-N. cyt-N is conserved poorly between human and mouse CD40, while cyt-C is highly conserved. However, single aa substitution of Glu-235 in cyt-N of human CD40 with Ala abolishes the binding of TRAF6 to cyt-N and NFkappaB activation by cyt-N. Conservation of this Glu between mouse and human CD40 strongly suggests that TRAF6 could link cyt-N to signals essential for CD40-mediated immune response. Furthermore, NFkappaB activation by cyt-C is inhibited by a kinase negative form of NFkappaB-inducing kinase more efficiently than that by cyt-N, consistent with the result that NFkappaB activation by TRAF2 and TRAF5 is inhibited by a kinase-negative form of NFkappaB-inducing kinase more efficiently than that by TRAF6. These results indicate that NFkappaB activating signals emanating from cyt-N and cyt-C are mediated by the different members of the TRAF family and could be regulated in a distinct manner. PMID- 9990008 TI - Principles of quasi-equivalence and Euclidean geometry govern the assembly of cubic and dodecahedral cores of pyruvate dehydrogenase complexes. AB - The pyruvate dehydrogenase multienzyme complex (Mr of 5-10 million) is assembled around a structural core formed of multiple copies of dihydrolipoyl acetyltransferase (E2p), which exhibits the shape of either a cube or a dodecahedron, depending on the source. The crystal structures of the 60-meric dihydrolipoyl acyltransferase cores of Bacillus stearothermophilus and Enterococcus faecalis pyruvate dehydrogenase complexes were determined and revealed a remarkably hollow dodecahedron with an outer diameter of approximately 237 A, 12 large openings of approximately 52 A diameter across the fivefold axes, and an inner cavity with a diameter of approximately 118 A. Comparison of cubic and dodecahedral E2p assemblies shows that combining the principles of quasi equivalence formulated by Caspar and Klug [Caspar, D. L. & Klug, A. (1962) Cold Spring Harbor Symp. Quant. Biol. 27, 1-4] with strict Euclidean geometric considerations results in predictions of the major features of the E2p dodecahedron matching the observed features almost exactly. PMID- 9990009 TI - Opposing actions of intact and N-terminal fragments of the human prolactin/growth hormone family members on angiogenesis: an efficient mechanism for the regulation of angiogenesis. AB - Angiogenesis, the process of development of a new microvasculature, is regulated by a balance of positive and negative factors. We show both in vivo and in vitro that the members of the human prolactin/growth hormone family, i.e., human prolactin, human growth hormone, human placental lactogen, and human growth hormone variant are angiogenic whereas their respective 16-kDa N-terminal fragments are antiangiogenic. The opposite actions are regulated in part via activation or inhibition of mitogen-activated protein kinase signaling pathway. In addition, the N-terminal fragments stimulate expression of type 1 plasminogen activator inhibitor whereas the intact molecules have no effect, an observation consistent with the fragments acting via separate receptors. The concept that a single molecule encodes both angiogenic and antiangiogenic peptides represents an efficient model for regulating the balance of positive and negative factors controlling angiogenesis. This hypothesis has potential physiological importance for the control of the vascular connection between the fetal and maternal circulations in the placenta, where human prolactin, human placental lactogen, and human growth hormone variant are expressed. PMID- 9990011 TI - Crystal structure of a dimeric chymotrypsin inhibitor 2 mutant containing an inserted glutamine repeat. AB - We have constructed mutants of chymotrypsin inhibitor 2 with short glutamine repeats inserted into its inhibitory loop. These mutants oligomerize when expressed in Escherichia coli. The dimer of a mutant with four glutamines now has been crystallized, and its structure has been solved by molecular replacement by using the wild-type monomer as a search model. The structure of each half of the dimer is found to be the same as that of the wild-type monomer, except around the glutamine insertion. It was proposed that the components of the oligomers are held together by hydrogen bonds between the main-chain and side-chain amides of the glutamine repeats. Instead, they appear to form by swapping domains on folding in E. coli, and the glutamine repeats connecting the components of the dimers are disordered. PMID- 9990010 TI - Dissecting Fas signaling with an altered-specificity death-domain mutant: requirement of FADD binding for apoptosis but not Jun N-terminal kinase activation. AB - Fas is a cell surface death receptor that regulates peripheral tolerance and lymphoid homeostasis. In many pathologic conditions, ectopic Fas activation mediates tissue destruction. Several proteins that can bind to the cytoplasmic death domain of Fas have been implicated in Fas signal transduction. Here we show that FADD, which couples Fas to pro-caspase-8, and, Daxx, which couples Fas to the Jun N-terminal kinase pathway, bind independently to the Fas death domain. We have isolated a death domain mutant, termed FasDelta, that selectively binds Daxx but not FADD. In tranfected tissue culture cells, FasDelta activated Jun N terminal kinase normally but was impaired in cell death induction. These results suggest that FADD and Daxx activate two independent pathways downstream of Fas and confirm the essential role of FADD binding in apoptosis induction. PMID- 9990012 TI - Structure, thermostability, and conformational flexibility of hen egg-white lysozyme dissolved in glycerol. AB - Hen egg-white lysozyme dissolved in glycerol containing 1% water was studied by using CD and amide proton exchange monitored by two-dimensional 1H NMR. The far- and near-UV CD spectra of the protein showed that the secondary and tertiary structures of lysozyme in glycerol were similar to those in water. Thermal melting of lysozyme in glycerol followed by CD spectral changes indicated unfolding of the tertiary structure with a Tm of 76.0 +/- 0.2 degreesC and no appreciable loss of the secondary structure up to 85 degreesC. This is in contrast to the coincident denaturation of both tertiary and secondary structures with Tm values of 74.8 +/- 0.4 degreesC and 74.3 +/- 0.7 degreesC, respectively, under analogous conditions in water. Quenched amide proton exchange experiments revealed a greater structural protection of amide protons in glycerol than in water for a majority of the slowly exchanging protons. The results point to a highly ordered, native-like structure of lysozyme in glycerol, with the stability exceeding that in water. PMID- 9990014 TI - Folding pathway of a lattice model for proteins. AB - The folding of a protein-like heteropolymer is studied by using direct simulation of a lattice model that folds rapidly to a well-defined "native" structure. The details of each molecular folding event depend on the random initial conformation as well as the random thermal fluctuations of the polymer. By analyzing the statistical properties of hundreds of folding events, a classical folding "pathway" for such a polymer is found that includes partially folded, on-pathway intermediates that are shown to be metastable equilibrium states of the polymer. These results are discussed in the context of the "classical" and "new" views of folding. PMID- 9990013 TI - Cooperative binding of ATP and MgADP in the sulfonylurea receptor is modulated by glibenclamide. AB - The ATP-sensitive potassium (KATP) channels in pancreatic beta cells are critical in the regulation of glucose-induced insulin secretion. Although electrophysiological studies provide clues to the complex control of KATP channels by ATP, MgADP, and pharmacological agents, the molecular mechanism of KATP-channel regulation remains unclear. The KATP channel is a heterooligomeric complex of SUR1 subunits of the ATP-binding-cassette superfamily with two nucleotide-binding folds (NBF1 and NBF2) and the pore-forming Kir6.2 subunits. Here, we report that MgATP and MgADP, but not the Mg salt of gamma-thio-ATP, stabilize the binding of prebound 8-azido-[alpha-32P]ATP to SUR1. Mutation in the Walker A and B motifs of NBF2 of SUR1 abolished this stabilizing effect of MgADP. These results suggest that SUR1 binds 8-azido-ATP strongly at NBF1 and that MgADP, either by direct binding to NBF2 or by hydrolysis of bound MgATP at NBF2, stabilizes prebound 8-azido-ATP binding at NBF1. The sulfonylurea glibenclamide caused release of prebound 8-azido-[alpha-32P]ATP from SUR1 in the presence of MgADP or MgATP in a concentration-dependent manner. This direct biochemical evidence of cooperative interaction in nucleotide binding of the two NBFs of SUR1 suggests that glibenclamide both blocks this cooperative binding of ATP and MgADP and, in cooperation with the MgADP bound at NBF2, causes ATP to be released from NBF1. PMID- 9990015 TI - Role of calpain in adipocyte differentiation. AB - Evidence is presented that the calcium-activated protease, calpain, is required for differentiation of 3T3-L1 preadipocytes into adipocytes induced by methylisobutylxanthine (a cAMP phosphodiesterase inhibitor), dexamethasone, and insulin. Calpain is expressed by preadipocytes and its level falls during differentiation. Exposure of preadipocytes to the calpain inhibitor N-acetyl-Leu Leu-norleucinal or overexpression of calpastatin, a specific endogenous inhibitor of calpain, blocks expression of adipocyte-specific genes, notably the CCAAT/enhancer-binding protein (C/EBP)alpha gene, and acquisition of the adipocyte phenotype. The inhibitor disrupts the differentiation-inducing effect of methylisobutylxanthine (by means of the cAMP-signaling pathway), but is without effect on differentiation induced by dexamethasone or insulin. N-acetyl Leu-Leu-norleucinal, or overexpression of calpastatin, inhibits reporter gene expression mediated by the C/EBPalpha gene promoter by preventing C/EBPbeta, a transcriptional activator of the C/EBPalpha gene, from binding to the promoter. These findings implicate calpain in the transcriptional activation of the C/EBPalpha gene, a process required for terminal adipocyte differentiation. PMID- 9990016 TI - Interactions between human cyclin T, Tat, and the transactivation response element (TAR) are disrupted by a cysteine to tyrosine substitution found in mouse cyclin T. AB - The transcriptional transactivator Tat from HIV binds to the transactivation response element (TAR) RNA to increase rates of elongation of viral transcription. Human cyclin T supports these interactions between Tat and TAR. In this study, we report the sequence of mouse cyclin T and identify the residues from positions 1 to 281 in human cyclin T that bind to Tat and TAR. Mouse cyclin T binds to Tat weakly and is unable to facilitate interactions between Tat and TAR. Reciprocal exchanges of the cysteine and tyrosine at position 261 in human and mouse cyclin T proteins also render human cyclin T inactive and mouse cyclin T active. These findings reveal the molecular basis for the restriction of Tat transactivation in rodent cells. PMID- 9990017 TI - Modulation of type M2 pyruvate kinase activity by the human papillomavirus type 16 E7 oncoprotein. AB - We report here that the E7 oncoprotein encoded by the oncogenic human papillomavirus (HPV) type 16 binds to the glycolytic enzyme type M2 pyruvate kinase (M2-PK). M2-PK occurs in a tetrameric form with a high affinity to its substrate phosphoenolpyruvate and a dimeric form with a low affinity to phosphoenolpyruvate, and the transition between both conformations regulates the glycolytic flux in tumor cells. The glycolytic intermediate fructose 1, 6 bisphosphate induces the reassociation of the dimeric to the tetrameric form of M2-PK. The expression of E7 in an experimental cell line shifts the equilibrium to the dimeric state despite a significant increase in the fructose 1,6 bisphosphate levels. Investigations of HPV-16 E7 mutants and the nononcogenic HPV 11 subtype suggest that the interaction of HPV-16 E7 with M2-PK may be linked to the transforming potential of the viral oncoprotein. PMID- 9990018 TI - The charged region of Hsp90 modulates the function of the N-terminal domain. AB - Hsp90, an abundant heat shock protein that is highly expressed even under physiological conditions, is involved in the folding of key molecules of the cellular signal transduction system such as kinases and steroid receptors. It seems to contain two chaperone sites differing in substrate specificity. Binding of ATP or the antitumor drug geldanamycin alters the substrate affinity of the N terminal chaperone site, whereas both substances show no influence on the C terminal one. In wild-type Hsp90 the fragments containing the chaperone sites are connected by a highly charged linker of various lengths in different organisms. As this linker region represents the most striking difference between bacterial and eukaryotic Hsp90s, it may be involved in a gain of function of eukaryotic Hsp90s. Here, we have analyzed a fragment of yeast Hsp90 consisting of the N terminal domain and the charged region (N272) in comparison with the isolated N terminal domain (N210). We show that the charged region causes an increase in the affinity of the N-terminal domain for nonnative protein and establishes a crosstalk between peptide and ATP binding. Thus, the binding of peptide to N272 decreases its affinity for ATP and geldanamycin, whereas the ATP-binding properties of the monomeric N-terminal domain N210 are not influenced by peptide binding. We propose that the charged region connecting the two chaperone domains plays an important role in regulating chaperone function of Hsp90. PMID- 9990020 TI - Dimethylallyl pyrophosphate is not the committed precursor of isopentenyl pyrophosphate during terpenoid biosynthesis from 1-deoxyxylulose in higher plants. AB - Cell cultures of Catharanthus roseus were supplied with [2-13C, 3-2H] deoxyxylulose or [2-13C,4-2H]1-deoxyxylulose. Lutein and chlorophylls were isolated from the cell mass, and hydrolysis of the chlorophyll mixtures afforded phytol. Isotope labeling patterns of phytol and lutein were determined by 2H NMR and 1H,2H-decoupled 13C NMR. From the data it must be concluded that the deuterium atom in position 3 of deoxyxylulose was incorporated into both isopentenyl pyrophosphate (IPP) and dimethylallyl pyrophosphate with a rate of 75% (with respect to the internal 13C label). The detected stereochemical signature implies that the label is located preferentially in the (E)-hydrogen atom of IPP. This preferential labeling, in turn, rules out dimethylallyl pyrophosphate as the compulsory precursor of IPP. In the experiment with [2-13C, 4-2H]1-deoxyxylulose, the 13C label was efficiently transferred to the terpenoids whereas the 2H label was completely washed out, most probably after IPP formation as a consequence of the isomerization and elongation process. In addition, the data cast light on the stereochemical course of the dehydrogenation and cyclization steps involved in the biosynthesis of lutein. PMID- 9990019 TI - A role for FEN-1 in nonhomologous DNA end joining: the order of strand annealing and nucleolytic processing events. AB - Eukaryotic repair of double-strand DNA breaks can occur either by homologous recombination or by nonhomologous DNA end joining (NHEJ). NHEJ relies on Ku70/86, XRCC4, DNA ligase IV, and DNA-dependent protein kinase. NHEJ involves a synapsis step in which the two ends are maintained in proximity, processing steps in which nucleases and polymerases act on the ends, an alignment step in which a few nucleotides of terminal homology guide the ends into preferred alignments, and a ligation step. Some of the steps, such as ligation, rely on a single enzymatic component. However, the processing steps begin and end with a wide array of alternative substrates and products, respectively, and likely involve multiple nucleases and polymerases. Given the alternative pathways that can be catalyzed by the remaining nucleases and polymerases, no one of these processing enzymes is likely to be essential. The only requirement for the processing enzymes, as a collective, is to generate a ligatable configuration, namely a ligatable nick on each strand. Here, we have tested the two major known 5'-specific nucleases of Saccharomyces cerevisiae for involvement in NHEJ. Whereas EXO1 does not appear to be involved to any detectable level, deleting RAD27 (FEN-1 of yeast) leads to a 4.4-fold reduction specifically of those NHEJ events predicted to proceed by means of 5' flap intermediates. Because Rad27/FEN-1 acts specifically at 5' flap structures, these results suggest that the NHEJ alignment step precedes nucleolytic processing steps in a significant fraction of NHEJ events. PMID- 9990021 TI - The retinitis pigmentosa GTPase regulator, RPGR, interacts with the delta subunit of rod cyclic GMP phosphodiesterase. AB - Recently, the retinitis pigmentosa 3 (RP3) gene has been cloned and named retinitis pigmentosa GTPase regulator (RPGR). The amino-terminal half of RPGR is homologous to regulator of chromosome condensation (RCC1), the nucleotide exchange factor for the small GTP-binding protein Ran. In a yeast two-hybrid screen we identified the delta subunit of rod cyclic GMP phosphodiesterase (PDEdelta) as interacting with the RCC1-like domain (RLD) of RPGR (RPGR392). The interaction of RPGR with PDEdelta was confirmed by pull-down assays and plasmon surface resonance. The binding affinity was determined to be 90 nM. Six missense mutations at evolutionary conserved residues within the RLD, which were found in RP3 patients, were analyzed by using the two-hybrid system. All missense mutations showed reduced interaction with PDEdelta. A non-RP3-associated missense substitution outside the RLD, V36F, did not abolish the interaction with PDEdelta. PDEdelta is widely expressed and highly conserved across evolution and is proposed to regulate the membrane insertion or solubilization of prenylated proteins, including the catalytic subunits of the PDE holoenzyme involved in phototransduction and small GTP-binding proteins of the Rab family. These results suggest that RPGR mutations give rise to retinal degeneration by dysregulation of intracellular processes that determine protein localization and protein transport. PMID- 9990022 TI - Mammalian subtilisin/kexin isozyme SKI-1: A widely expressed proprotein convertase with a unique cleavage specificity and cellular localization. AB - Using reverse transcriptase-PCR and degenerate oligonucleotides derived from the active-site residues of subtilisin/kexin-like serine proteinases, we have identified a highly conserved and phylogenetically ancestral human, rat, and mouse type I membrane-bound proteinase called subtilisin/kexin-isozyme-1 (SKI-1). Computer databank searches reveal that human SKI-1 was cloned previously but with no identified function. In situ hybridization demonstrates that SKI-1 mRNA is present in most tissues and cells. Cleavage specificity studies show that SKI-1 generates a 28-kDa product from the 32-kDa brain-derived neurotrophic factor precursor, cleaving at an RGLT downward arrowSL bond. In the endoplasmic reticulum of either LoVo or HK293 cells, proSKI-1 is processed into two membrane bound forms of SKI-1 (120 and 106 kDa) differing by the nature of their N glycosylation. Late along the secretory pathway some of the membrane-bound enzyme is shed into the medium as a 98-kDa form. Immunocytochemical analysis of stably transfected HK293 cells shows that SKI-1 is present in the Golgi apparatus and within small punctate structures reminiscent of endosomes. In vitro studies suggest that SKI-1 is a Ca2+-dependent serine proteinase exhibiting a wide pH optimum for cleavage of pro-brain-derived neurotrophic factor. PMID- 9990023 TI - Posttranslational modification of Galphao1 generates Galphao3, an abundant G protein in brain. AB - Galphao, the most abundant G protein in mammalian brain, occurs at least in two subforms, i.e., Galphao1 and Galphao2, derived by alternative splicing of the mRNA. A third Galphao1-related isoform, Galphao3, has been purified, representing about 30% of total Go in brain. Initial studies revealed distinct biochemical properties of Galphao3 as compared with other Galphao isoforms. In matrix assisted laser desorption/ionization peptide mass mapping of gel-isolated Galphao1 and Galphao3, C-terminal peptides showed a difference of +1 Da for Galphao3. Nanoelectrospray tandem mass spectrometry sequencing revealed an Asp instead of an Asn at position 346 of Galphao3. Gel electrophoretic analysis of recombinant Galphao3 showed the same mobility as native Galphao3 but distinct to Galphao1. The conversion of 346Asn-->Asp changed the signaling properties, including the velocity of the basal guanine nucleotide-exchange reaction, which points to the involvement of the C terminus in basal guanosine 5'-[gamma thio]triphosphate binding. No cDNA coding for Galphao3 was detected, suggesting an enzymatic deamidation of Galphao1 by a yet-unidentified activity. Therefore, Galpha heterogeneity is generated not only at the DNA or RNA levels, but also at the protein level. The relative amount of Galphao1 and Galphao3 differed from cell type to cell type, indicating an additional principle of G protein regulation. PMID- 9990024 TI - The neurotransmitter receptor-anchoring protein gephyrin reconstitutes molybdenum cofactor biosynthesis in bacteria, plants, and mammalian cells. AB - The molybdenum cofactor (Moco), a highly conserved pterin compound complexing molybdenum, is required for the enzymatic activities of all molybdenum enzymes except nitrogenase. Moco is synthesized by a unique and evolutionarily old pathway that requires the activities of at least six gene products. Some of the proteins involved in bacterial, plant, and invertebrate Moco biosynthesis show striking homologies to the primary structure of gephyrin, a polypeptide required for the clustering of inhibitory glycine receptors in postsynaptic membranes in the rat central nervous system. Here, we show that gephyrin binds with high affinity to molybdopterin, the metabolic precursor of Moco. Furthermore, gephyrin expression can reconstitute Moco biosynthesis in Moco-deficient bacteria, a molybdenum-dependent mouse cell line, and a Moco-deficient plant mutant. Conversely, inhibition of gephyrin expression by antisense RNA expression in cultured murine cells reduces their Moco content significantly. These data indicate that in addition to clustering glycine receptors, gephyrin also is involved in Moco biosynthesis and illustrate the remarkable conservation of its function in Moco biosynthesis throughout phylogeny. PMID- 9990025 TI - rRNA-complementarity in the 5' untranslated region of mRNA specifying the Gtx homeodomain protein: evidence that base- pairing to 18S rRNA affects translational efficiency. AB - Numerous eukaryotic mRNAs contain sequences complementary to segments of the 18S and 28S rRNAs. Previous studies raised the possibility that these complementarities might allow mRNA-rRNA interactions and affect rates of translation. In the present study, we investigated the mRNA encoding the mouse Gtx homeodomain protein. This mRNA contains within its 5' untranslated region (UTR) a segment that is complementary to two regions of the 18S rRNA, located at nucleotides 701-741 and 1104-1136. A Gtx RNA probe containing this complementarity could be photochemically cross-linked to ribosomal subunits through a linkage to 18S rRNA but not to 28S rRNA. Oligonucleotide-directed RNase H digestion of the rRNA and a reverse transcription analysis localized the cross linked probe to the complementary segment of 18S rRNA at nucleotides 1104-1136 but not at nucleotides 701-741. To determine whether complementarity in the Gtx mRNA affected translation, a mutational analysis was performed with a Gtx luciferase fusion construct and four related constructs with altered complementarity to the 18S rRNA. These constructs were examined for their ability to be translated in cell-free lysates prepared from P19 embryonal carcinoma and C6 glioma cell lines and after cellular transfection into these same cell lines. In both cell-free translation and transfection studies, the rate of translation decreased more than 9-fold as the degree of complementarity to nucleotides 1104 1136 of the 18S rRNA increased. We hypothesize that segments complementary to rRNA, such as those contained within the Gtx mRNA, form a category of cis-acting regulatory elements in mRNAs that affect translation by base pairing to rRNA within ribosomes. PMID- 9990026 TI - Histone modification governs the cell cycle regulation of a replication independent chromatin assembly pathway in Saccharomyces cerevisiae. AB - We describe a replication-independent, cell cycle-regulated chromatin assembly pathway in budding yeast. The activity of this pathway is low in S phase extracts but is very high in G2, M, and G1 cell extracts, with peak activity in late M/early G1. The cell cycle regulation of this pathway requires a specific pattern of posttranslational modification of histones H3 and/or H4, which is distinct for H3/H4 present in S phase versus M and G1 phase cell extracts. Histone H3/H4 modification is therefore important for the reciprocal control of replication dependent and -independent chromatin assembly pathways during the cell cycle. PMID- 9990027 TI - Forced unfolding of the fibronectin type III module reveals a tensile molecular recognition switch. AB - The 10th type III module of fibronectin possesses a beta-sandwich structure consisting of seven beta-strands (A-G) that are arranged in two antiparallel sheets. It mediates cell adhesion to surfaces via its integrin binding motif, Arg78, Gly79, and Asp80 (RGD), which is placed at the apex of the loop connecting beta-strands F and G. Steered molecular dynamics simulations in which tension is applied to the protein's terminal ends reveal that the beta-strand G is the first to break away from the module on forced unfolding whereas the remaining fold maintains its structural integrity. The separation of strand G from the remaining fold results in a gradual shortening of the distance between the apex of the RGD containing loop and the module surface, which potentially reduces the loop's accessibility to surface-bound integrins. The shortening is followed by a straightening of the RGD-loop from a tight beta-turn into a linear conformation, which suggests a further decrease of affinity and selectivity to integrins. The RGD-loop therefore is located strategically to undergo strong conformational changes in the early stretching stages of the module and thus constitutes a mechanosensitive control of ligand recognition. PMID- 9990028 TI - Critical role of conserved proline residues in the transmembrane segment 4 voltage sensor function and in the gating of L-type calcium channels. AB - The fourth transmembrane segment (S4) has been shown to function as a voltage sensor in voltage-gated channels. On membrane depolarization, a stretch of S4 moves outward and initiates a number of conformational changes that ultimately lead to channel opening. Conserved proline residues are in the middle of the S4 of motifs I and III in voltage-dependent Ca2+ channels. Because proline often introduces a "kink" into a helical structure of proteins, these residues might have an intrinsic function in the voltage sensor. Here, we report that the removal of S4 prolines results in a dramatic shortening of channel open time whereas the introduction of extra prolines to the corresponding positions in motif IIS4 and IVS4 lengthens channel open time. The number of S4s with a proline residue showed a clear positive correlation with the mean open time of the channel. The mean open time was >11-fold longer for a channel mutagenized to have prolines in all four S4s compared with a channel that had no prolines in the S4 region. Additionally, prolines in the S4s slowed activation kinetics and shifted the voltage dependence of activation and inactivation in a hyperpolarized direction. Our results strongly suggest that proline residues in the S4s are critical for stabilizing the open state of the channel. Moreover, it is suggested that motif IS4 and IIIS4 contribute to the channel opening more efficiently than motif IIS4 and IVS4. PMID- 9990029 TI - Structural analysis at 2.2 A of orthorhombic crystals presents the asymmetry of the allophycocyanin-linker complex, AP.LC7.8, from phycobilisomes of Mastigocladus laminosus. AB - An electrophoretically purified allophycocyanin-linker complex, AP. LC7.8, from phycobilisomes of Mastigocladus laminosus has been crystallized in the orthorhombic space group P212121. Cryocrystallographic x-ray measurements enabled the structural analysis of the complex at a resolution of 2.2 A. The asymmetric unit contains two side-to-side associated "trimeric" (alphabeta)3 allophycocyanin complexes comprising the linker polypeptide in a defined orientation inside the trimer. The linker representing a protein fold related to the prosegment of procarboxypeptidase A is in contact with only two of the three beta-subunits and directly interacts with the corresponding chromophores of these proteins. In addition to a modulation of the chromophores' spectral properties, the linker polypeptide attracts the alphabeta-subcomplexes, thereby bringing the beta chromophores closer together. These results will enable interpretations of energy transfer mechanisms within phycobiliproteins. PMID- 9990031 TI - Confocal fluorescence coincidence analysis: an approach to ultra high-throughput screening. AB - Fluorescence-based assay technologies play an increasing role in high-throughput screening. They can be classified into different categories: fluorescence polarization, time-resolved fluorescence, fluorescence resonance energy transfer, and fluorescence correlation spectroscopy. In this work we present an alternative analytical technique for high-throughput screening, which we call confocal fluorescence coincidence analysis. Confocal fluorescence coincidence analysis extracts fluorescence fluctuations that occur coincidently in two different spectral ranges from a tiny observation volume of below 1 fl. This procedure makes it possible to monitor whether an association between molecular fragments that are labeled with different fluorophores is established or broken. Therefore, it provides access to the characterization of a variety of cleavage and ligation reactions in biochemistry. Confocal fluorescence coincidence analysis is a very sensitive and ultrafast technique with readout times of 100 ms and below. This feature is demonstrated by means of a homogeneous assay for restriction endonuclease EcoRI. The presented achievements break ground for throughput rates as high as 10(6) samples per day with using only small amounts of sample substance and therefore constitute a solid base for screening applications in drug discovery and evolutionary biotechnology. PMID- 9990030 TI - Coevolutionary analysis of resistance-evading peptidomimetic inhibitors of HIV-1 protease. AB - We have developed a coevolutionary method for the computational design of HIV-1 protease inhibitors selected for their ability to retain efficacy in the face of protease mutation. For HIV-1 protease, typical drug design techniques are shown to be ineffective for the design of resistance-evading inhibitors: An inhibitor that is a direct analogue of one of the natural substrates will be susceptible to resistance mutation, as will inhibitors designed to fill the active site of the wild-type or a mutant enzyme. Two design principles are demonstrated: (i) For enzymes with broad substrate specificity, such as HIV-1 protease, resistance evading inhibitors are best designed against the immutable properties of the active site-the properties that must be conserved in any mutant protease to retain the ability to bind and cleave all of the native substrates. (ii) Robust resistance-evading inhibitors can be designed by optimizing activity simultaneously against a large set of mutant enzymes, incorporating as much of the mutational space as possible. PMID- 9990032 TI - An approach to long-range electron transfer mechanisms in metalloproteins: in situ scanning tunneling microscopy with submolecular resolution. AB - In situ scanning tunneling microscopy (STM) of redox molecules, in aqueous solution, shows interesting analogies and differences compared with interfacial electrochemical electron transfer (ET) and ET in homogeneous solution. This is because the redox level represents a deep indentation in the tunnel barrier, with possible temporary electronic population. Particular perspectives are that both the bias voltage and the overvoltage relative to a reference electrode can be controlled, reflected in spectroscopic features when the potential variation brings the redox level to cross the Fermi levels of the substrate and tip. The blue copper protein azurin adsorbs on gold(111) via a surface disulfide group. Well resolved in situ STM images show arrays of molecules on the triangular gold(111) terraces. This points to the feasibility of in situ STM of redox metalloproteins directly in their natural aqueous medium. Each structure also shows a central brighter contrast in the constant current mode, indicative of 2- to 4-fold current enhancement compared with the peripheral parts. This supports the notion of tunneling via the redox level of the copper atom and of in situ STM as a new approach to long-range electron tunneling in metalloproteins. PMID- 9990033 TI - A human cell-surface receptor for xenotropic and polytropic murine leukemia viruses: possible role in G protein-coupled signal transduction. AB - Although present in many copies in the mouse genome, xenotropic murine leukemia viruses cannot infect cells from laboratory mice because of the lack of a functional cell surface receptor required for virus entry. In contrast, cells from many nonmurine species, including human cells, are fully permissive. Using an expression library approach, we isolated a cDNA from HeLa cell RNA that conferred susceptibility to xenotropic envelope protein binding and virus infection when expressed in nonpermissive cells. The deduced product is a 696-aa multiple-membrane spanning molecule, is widely expressed in human tissues, and shares homology with nematode, fly, and plant proteins of unknown function as well as with the yeast SYG1 protein, which has been shown to interact with a G protein. This molecule also acts as a receptor for polytropic murine leukemia viruses, consistent with observed interference between xenotropic and polytropic viruses in some cell types. This xenotropic and polytropic retrovirus receptor (XPR1) is the fourth identified molecule having multiple membrane spanning domains among mammalian type C oncoretrovirus receptors and may play a role in G protein-coupled signal transduction, as do the chemokine receptors required for HIV entry. PMID- 9990034 TI - Phosphorylation of presenilin-2 regulates its cleavage by caspases and retards progression of apoptosis. AB - Mutations within the Presenilin-2 (PS-2) gene are associated with early onset familial Alzheimer's disease. The gene encodes a polytopic transmembrane protein that undergoes endoproteolytic processing resulting in the generation of N terminal and C-terminal fragments (CTFs). PS-2 is also cleaved by proteases of the caspase family during apoptotic cell death. CTFs of PS-2 were shown to inhibit apoptosis, suggesting an important role in the regulation of programmed cell death. Recently, we found that the CTF of PS-2 is phosphorylated in vivo. We mapped the in vivo phosphorylation sites of PS-2 to serine residues 327 and 330, which are localized immediately adjacent to the cleavage sites of caspases after aspartate residues 326 and 329. Phosphorylation of PS-2 inhibits its cleavage by caspase-3. This effect can be mimicked by substitutions of serines 327 and 330 by aspartate or glutamate. In addition, the uncleavable form of PS-2 CTF was found to enhance its antiapoptotic properties, leading to a slower progression of apoptosis. These results demonstrate that PS-2 cleavage as well as its function in apoptosis can be regulated by protein phosphorylation. Alterations in the phosphorylation of PS-2 may therefore promote the pathogenesis of AD by affecting the susceptibility of neurons to apoptotic stimuli. PMID- 9990035 TI - Differential regulation of maternal vs. paternal centrosomes. AB - Centrosomes are the main microtubule-organizing centers in animal cells. During meiosis and mitosis, two centrosomes form the poles that direct the assembly of a bipolar spindle, thus ensuring the accurate segregation of chromosomes. Cells cannot tolerate the presence of more than two active centrosomes during meiosis or mitosis because doing so results in the formation of multipolar spindles, infidelity in chromosome segregation, and aneuploidy. Here, we show that fertilization of Spisula solidissima oocytes results in cells that contain three active centrosomes, two maternal and one paternal. During meiosis I, the paternal centrosome's ability to nucleate microtubules is selectively shut off while maternal centrosomes remain competent to nucleate microtubules and assemble asters in the same cytoplasm. We propose that embryos can identify paternal vs. maternal centrosomes and can control them differentially. PMID- 9990036 TI - Catalytic subunit of DNA-dependent protein kinase: impact on lymphocyte development and tumorigenesis. AB - The DNA-dependent protein kinase (DNA-PK) consists of a heterodimer DNA-binding complex, Ku70 and Ku80, and a large catalytic subunit, DNA-PKcs. To examine the role of DNA-PKcs in lymphocyte development, radiation sensitivity, and tumorigenesis, we disrupted the mouse DNA-PKcs by homologous recombination. DNA PKcs-null mice exhibit neither growth retardation nor a high frequency of T cell lymphoma development, but show severe immunodeficiency and radiation hypersensitivity. In contrast to the Ku70-/- and Ku80-/- phenotype, DNA-PKcs-null mice are blocked for V(D)J coding but not for signal-end joint formation. Furthermore, inactivation of DNA-PKcs leads to hyperplasia and dysplasia of the intestinal mucosa and production of aberrant crypt foci, suggesting a novel role of DNA-PKcs in tumor suppression. PMID- 9990038 TI - Mechanism of biological synergy between cellular Src and epidermal growth factor receptor. AB - Overexpression of both cellular Src (c-Src) and the epidermal growth factor receptor (EGFR) occurs in many of the same human tumors, suggesting that they may functionally interact and contribute to the progression of cancer. Indeed, in murine fibroblasts, overexpression of c-Src has been shown to potentiate the mitogenic and tumorigenic capacity of the overexpressed EGFR. Potentiation correlated with the ability of c-Src to physically associate with the activated EGFR and the appearance of two unique in vivo phosphorylations on the receptor (Tyr-845 and Tyr-1101). Using stable cell lines of C3H10T1/2 murine fibroblasts that contain kinase-deficient (K-) c-Src and overexpressed wild-type EGFR, we show that the kinase activity of c-Src is required for both the biological synergy with the receptor and the phosphorylations on the receptor, but not for the association of c-Src with the receptor. In transient transfection assays, not only epidermal growth factor but also serum- and lysophosphatidic acid-induced DNA synthesis was ablated in a dominant-negative fashion by a Y845F mutant of the EGFR, indicating that c-Src-induced phosphorylation of Y845 is critical for the mitogenic response to both the EGFR and a G protein-coupled receptor (lysophosphatidic acid receptor). Unexpectedly, the Y845F mutant EGFR was found to retain its full kinase activity and its ability to activate the adapter protein SHC and extracellular signal-regulated kinase ERK2 in response to EGF, demonstrating that the mitogenic pathway involving phosphorylation of Y845 is independent of ERK2-activation. The application of these findings to the development of novel therapeutics for human cancers that overexpress c-Src and EGFR is discussed. PMID- 9990037 TI - Identification of SSF1, CNS1, and HCH1 as multicopy suppressors of a Saccharomyces cerevisiae Hsp90 loss-of-function mutation. AB - Hsp90 functions in a multicomponent chaperone system to promote the maturation and maintenance of a diverse, but specific, set of target proteins that play key roles in the regulation of cell growth and development. To identify additional components of the Hsp90 chaperone system and its targets, we searched for multicopy suppressors of various temperature-sensitive mutations in the yeast Hsp90 gene, HSP82. Three suppressors were isolated for one Hsp90 mutant (glutamate --> lysine at amino acid 381). Each exhibited a unique, allele specific pattern of suppression with other Hsp90 mutants and had unique structural and biological properties. SSF1 is a member of an essential gene family and functions in the response to mating pheromones. CNS1 is an essential gene that encodes a component of the Hsp90 chaperone machinery. The role of HCH1 is unknown; its sequence has no strong homology to any protein of known function. SSF1 and CNS1 were weak suppressors, whereas HCH1 restored wild-type growth rates at all temperatures tested to cells expressing the E381K mutant. Overexpression of CNS1 or HCH1, but not SSF1, enhanced the maturation of a heterologous Hsp90 target protein, p60(v-src). These results suggest that like Cns1p, Hch1p is a general modulator of Hsp90 chaperone functions, whereas Ssf1p likely is either an Hsp90 target protein or functions in the same pathway as an Hsp90 target protein. PMID- 9990039 TI - Specificities of CD40 signaling: involvement of TRAF2 in CD40-induced NF-kappaB activation and intercellular adhesion molecule-1 up-regulation. AB - Several tumor necrosis factor receptor-associated factor (TRAF) family proteins including TRAF2, TRAF3, TRAF5, and TRAF6, as well as Jak3, have been implicated as potential mediators of CD40 signaling. An extensive in vitro binding study indicated that TRAF2 and TRAF3 bind to the CD40 cytoplasmic tail (CD40ct) with much higher affinity than TRAF5 and TRAF6 and that TRAF2 and TRAF3 bind to different residues of the CD40ct. Using CD40 mutants incapable of binding TRAF2, TRAF3, or Jak3, we found that the TRAF2-binding site of the CD40ct is critical for NF-kappaB and stress-activated protein kinase activation, as well as the up regulation of the intercellular adhesion molecule-1 (ICAM-1) gene, whereas binding of TRAF3 and Jak3 is dispensable for all of these functions. Overexpression of a dominantly active IkappaBalpha strongly inhibited CD40 induced NF-kappaB activation, ICAM-1 promoter activity, and cell-surface ICAM-1 up-regulation. These studies suggest a potential signal transduction pathway from the CD40 receptor to the transcriptional activation of the ICAM-1 gene. PMID- 9990040 TI - G1 cell cycle arrest and apoptosis induction by nuclear Smad4/Dpc4: phenotypes reversed by a tumorigenic mutation. AB - The tumor suppressor Smad4/Dpc4 is a transcription activator that binds specific DNA sequences and whose nuclear localization is induced after exposure to type beta transforming growth factor-like cytokines. We explored an inducible system in which Smad4 protein is activated by translocation to the nucleus when cell lines that stably express wild-type or mutant Smad4 proteins fused to a murine estrogen receptor domain are treated with 4-hydroxytamoxifen. This induced Smad4 mediated transcriptional activation and a decrease in growth rate, attributable to a cell cycle arrest at the G1 phase and an induction of apoptosis. A tumor derived mutation (Arg-100 --> Thr) affecting a residue critical for DNA-binding demonstrated an "oncogenic" phenotype, having decreases in both the G1 fraction and apoptosis and, consequently, an augmentation of population growth. This model should be useful in the exploration and control of components that lie further downstream in the Smad4 tumor-suppressor pathway. PMID- 9990041 TI - Identification of the cyclin D1 gene as a target of activating transcription factor 2 in chondrocytes. AB - Endochondral bone growth is regulated by the rates of chondrocyte proliferation and differentiation. However, the intracellular mechanisms regulating these processes are poorly understood. Recently, interruption of the gene encoding the transcription factor activating transcription factor 2 (ATF-2) was shown to inhibit proliferation of chondrocytes in mice [Reimold, A. M., et al. (1996) Nature (London) 379, 262-265]. The target genes of ATF-2 that are responsible for this phenotype remain unknown. Here we report that the cyclin D1 gene is a direct target of ATF-2 in chondrocytes. ATF-2 is present in nuclear extracts from chondrogenic cell lines and binds, as a complex with a CRE-binding protein (CREB)/CRE modulator protein, to the cAMP response element (CRE) in the cyclin D1 promoter. Mutation of the cyclin D1 CRE caused a 78% reduction in the activity of the promoter in chondrocytes. Overexpression of ATF-2 in chondrocytes enhanced activity of the cyclin D1 promoter 3. 5-fold. In contrast, inhibition of endogenous ATF-2 or CREB by expression of dominant-negative inhibitors of CREB and ATF-2 significantly reduced the activity of the promoter in chondrocytes through the CRE. In addition, levels of cyclin D1 protein are greatly reduced in the chondrocytes of ATF-2-deficient mice. These data identify the cyclin D1 gene as a direct target of ATF-2 in chondrocytes and suggest that reduced expression of cyclin D1 contributes to the defective cartilage development of these mice. PMID- 9990042 TI - The molecular chaperone Hsp90 can negatively regulate the activity of a glucocorticosteroid-dependent promoter. AB - Hsp90, a molecular chaperone required for the functioning of glucocorticosteroid receptor (GR), ensures, by direct interaction, the conformational competence of the steroid-binding pocket. In addition to having this positive function, Hsp90 maintains steroid receptors in an inactive form in the absence of hormone. However, neither the participation of Hsp90 once the pathway has been activated by the ligand nor the importance of increased Hsp90 levels in determining the amplitude of the response has ever been assessed directly. Here, by increasing the Hsp90/GR ratio in the nuclear compartment, we found an attenuation of the response to glucocorticosteroids that was not due to a nonspecific or toxic effect of the Hsp90 modified by nuclear targeting. Since this negative effect was more pronounced at high levels of hormone, when receptor and Hsp90 are maximally dissociated, the possibility of an interaction between Hsp90 and GR, already activated to a DNA-binding form, was directly investigated. Indeed GR, after in vivo activation by ligand, was still able to reassociate with Hsp90, suggesting that this interaction plays a role in vivo, possibly in receptor recycling. Moreover, the GR binding to its DNA response element was inhibited by an excess of Hsp90, pointing to a function of Hsp90 in the nuclear compartment. It is thus proposed that an increased Hsp90/GR ratio influences the responsiveness to ligand at a step that is after receptor activation. This increased ratio may be of pathophysiological relevance in the different circumstances that lead to an elevated level of nuclear Hsp90. PMID- 9990043 TI - Head-specific gene expression in Hydra: complexity of DNA- protein interactions at the promoter of ks1 is inversely correlated to the head activation potential. AB - To gain insight into the molecular mechanisms that direct position-dependent gene expression in the simple and evolutionarily old metazoan Hydra, we have examined DNA-protein interactions in the 1.5-kb cis regulatory region of the head-specific gene ks1. In vitro footprinting and gel-retardation techniques have been used to map the location of all protein-binding sites. To our surprise, we found substantially more proteins binding to ks1 promoter elements in nuclear extract from basal (gastric) than from apical (head- and tentacle-formation zone) cells. One of these proteins is the homeobox protein Cnox-2. In the head regeneration deficient mutant reg-16, an increased level of nuclear protein binds to ks1 promoter elements. Treatment of polyps with the ks1-inducing phorbol ester 12-O tetradecanoylphorbol 13-acetate (TPA) resulted in reduced binding of nuclear proteins to the ks1 cis regulatory region. As activation of ks1 transcription is correlated with the absence of nuclear proteins binding to the ks1 promoter, we propose that the majority of these proteins act as transcriptional repressors. In this view, the gradient of head activation along the Hydra body axis is caused by a decreasing amount of inhibitory factors, rather than an increasing amount of activators, toward the head. Thus, inhibitory mechanisms might have played a crucial role in regulating position-dependent gene activation during early metazoan evolution. PMID- 9990044 TI - Targeted disruption of gene function in Drosophila by RNA interference (RNA-i): a role for nautilus in embryonic somatic muscle formation. AB - The expression of the MyoD gene homolog, nautilus (nau), in the Drosophila embryo defines a subset of mesodermal cells known as the muscle "pioneer" or "founder" cells. These cells are thought to establish the future muscle pattern in each hemisegment. Founders appear to recruit fusion-competent mesodermal cells to establish a particular muscle fiber type. In support of this concept every somatic muscle in the embryo is associated with one or more nautilus-positive cells. However, because of the lack of known (isolated) nautilus mutations, no direct test of the founder cell hypothesis has been possible. We now have utilized toxin ablation and genetic interference by double-stranded RNA (RNA interference or RNA-i) to determine both the role of the nautilus-expressing cells and the nautilus gene, respectively, in embryonic muscle formation. In the absence of nautilus-expressing cells muscle formation is severely disrupted or absent. A similar phenotype is observed with the elimination of the nautilus gene product by genetic interference upon injection of nautilus double-stranded RNA. These results define a crucial role for nautilus in embryonic muscle formation. The application of RNA interference to a variety of known Drosophila mutations as controls gave phenotypes essentially indistinguishable from the original mutation. RNA-i provides a powerful approach for the targeted disruption of a given genetic function in Drosophila. PMID- 9990045 TI - Expression of a murine homologue of the inhibitor of apoptosis protein is related to cell proliferation. AB - The inhibitor of apoptosis (IAP) proteins form a highly conserved gene family that prevents cell death in response to a variety of stimuli. Herein we describe a newly defined murine IAP, designated Tiap, that proved to be a murine homologue of human survivin based on sequence comparison. TIAP has one baculovirus IAP repeat and lacks a C-terminal RING finger motif. TIAP interacted with the processed form of caspase 3 and inhibited caspase-induced cell death. Histological examinations revealed that TIAP is expressed in growing tissues such as thymus, testis, and intestine of adult mice and many tissues of embryos. In in vitro studies, TIAP was induced in splenic T cells activated with anti-CD3 antibody or Con A, and the expression of TIAP was up-regulated in synchronized NIH 3T3 cells at S to G2/M phase of the cell cycle. We propose that during cell proliferation, cellular protective activity may be augmented with inducible IAPs such as TIAP. PMID- 9990046 TI - Biodiversity and ecosystem productivity in a fluctuating environment: the insurance hypothesis. AB - Although the effect of biodiversity on ecosystem functioning has become a major focus in ecology, its significance in a fluctuating environment is still poorly understood. According to the insurance hypothesis, biodiversity insures ecosystems against declines in their functioning because many species provide greater guarantees that some will maintain functioning even if others fail. Here we examine this hypothesis theoretically. We develop a general stochastic dynamic model to assess the effects of species richness on the expected temporal mean and variance of ecosystem processes such as productivity, based on individual species' productivity responses to environmental fluctuations. Our model shows two major insurance effects of species richness on ecosystem productivity: (i) a buffering effect, i.e., a reduction in the temporal variance of productivity, and (ii) a performance-enhancing effect, i.e., an increase in the temporal mean of productivity. The strength of these insurance effects is determined by three factors: (i) the way ecosystem productivity is determined by individual species responses to environmental fluctuations, (ii) the degree of asynchronicity of these responses, and (iii) the detailed form of these responses. In particular, the greater the variance of the species responses, the lower the species richness at which the temporal mean of the ecosystem process saturates and the ecosystem becomes redundant. These results provide a strong theoretical foundation for the insurance hypothesis, which proves to be a fundamental principle for understanding the long-term effects of biodiversity on ecosystem processes. PMID- 9990047 TI - Organization of an echinoderm Hox gene cluster. AB - The Strongylocentrotus purpuratus genome contains a single ten-gene Hox complex >0.5 megabase in length. This complex was isolated on overlapping bacterial artificial chromosome and P1 artificial chromosome genomic recombinants by using probes for individual genes and by genomic walking. Echinoderm Hox genes of Paralog Groups (PG) 1 and 2 are reported. The cluster includes genes representing all paralog groups of vertebrate Hox clusters, except that there is a single gene of the PG4-5 types and only three genes of the PG9-12 types. The echinoderm Hox gene cluster is essentially similar to those of the bilaterally organized chordates, despite the radically altered pentameral body plans of these animals. PMID- 9990048 TI - Patterns of nucleotide substitution in Drosophila and mammalian genomes. AB - To estimate patterns of molecular evolution of unconstrained DNA sequences, we used maximum parsimony to separate phylogenetic trees of a non-long terminal repeat retrotransposable element into either internal branches, representing mainly the constrained evolution of active lineages, or into terminal branches, representing mainly nonfunctional "dead-on-arrival" copies that are unconstrained by selection and evolve as pseudogenes. The pattern of nucleotide substitutions in unconstrained sequences is expected to be congruent with the pattern of point mutation. We examined the retrotransposon Helena in the Drosophila virilis species group (subgenus Drosophila) and the Drosophila melanogaster species subgroup (subgenus Sophophora). The patterns of point mutation are indistinguishable, suggesting considerable stability over evolutionary time (40 60 million years). The relative frequencies of different point mutations are unequal, but the "transition bias" results largely from an approximately 2-fold excess of G.C to A.T substitutions. Spontaneous mutation is biased toward A.T base pairs, with an expected mutational equilibrium of approximately 65% A + T (quite similar to that of long introns). These data also enable the first detailed comparison of patterns of point mutations in Drosophila and mammals. Although the patterns are different, all of the statistical significance comes from a much greater rate of G.C to A.T substitution in mammals, probably because of methylated cytosine "hotspots." When the G.C to A.T substitutions are discounted, the remaining differences are considerably reduced and not statistically significant. PMID- 9990049 TI - The Arabidopsis thaliana proton transporters, AtNhx1 and Avp1, can function in cation detoxification in yeast. AB - Overexpression of the Arabidopsis thaliana vacuolar H+-pyrophosphatase (AVP1) confers salt tolerance to the salt-sensitive ena1 mutant of Saccharomyces cerevisiae. Suppression of salt sensitivity requires two ion transporters, the Gef1 Cl- channel and the Nhx1 Na+/H+ exchanger. These two proteins colocalize to the prevacuolar compartment of yeast and are thought to be required for optimal acidification of this compartment. Overexpression of AtNHX1, the plant homologue of the yeast Na+/H+ exchanger, suppresses some of the mutant phenotypes of the yeast nhx1 mutant. Moreover, the level of AtNHX1 mRNA in Arabidopsis is increased in the presence of NaCl. The regulation of AtNHX1 by NaCl and the ability of the plant gene to suppress the yeast nhx1 mutant suggest that the mechanism by which cations are detoxified in yeast and plants may be similar. PMID- 9990050 TI - Global response of Saccharomyces cerevisiae to an alkylating agent. AB - DNA chip technology enables simultaneous examination of how approximately 6,200 Saccharomyces cerevisiae gene transcript levels, representing the entire genome, respond to environmental change. By using chips bearing oligonucleotide arrays, we show that, after exposure to the alkylating agent methyl methanesulfonate, approximately 325 gene transcript levels are increased and approximately 76 are decreased. Of the 21 genes that already were known to be induced by a DNA damaging agent, 18 can be scored as inducible in this data set, and surprisingly, most of the newly identified inducible genes are induced even more strongly than these 18. We examined 42 responsive and 8 nonresponsive ORFs by conventional Northern blotting, and 48 of these 50 ORFs responded as they did by DNA chip analysis, with magnitudes displaying a correlation coefficient of 0.79. Responsive genes fall into several expected and many unexpected categories. Evidence for the induction of a program to eliminate and replace alkylated proteins is presented. PMID- 9990051 TI - Lethal mutagenesis of HIV with mutagenic nucleoside analogs. AB - The human immunodeficiency virus (HIV) replicates its genome and mutates at exceptionally high rates. As a result, the virus is able to evade immunological and chemical antiviral agents. We tested the hypothesis that a further increase in the mutation rate by promutagenic nucleoside analogs would abolish viral replication. We evaluated deoxynucleoside analogs for lack of toxicity to human cells, incorporation by HIV reverse transcriptase, resistance to repair when incorporated into the DNA strand of an RNA.DNA hybrid, and mispairing at high frequency. Among the candidates tested, 5-hydroxydeoxycytidine (5-OH-dC) fulfilled these criteria. In seven of nine experiments, the presence of this analog resulted in the loss of viral replicative potential after 9-24 sequential passages of HIV in human CEM cells. In contrast, loss of viral replication was not observed in 28 control cultures passaged in the absence of the nucleoside analog, nor with other analogs tested. Sequence analysis of a portion of the HIV reverse transcriptase gene demonstrated a disproportionate increase in G --> A substitutions, mutations predicted to result from misincorporation of 5-OH-dC into the cDNA during reverse transcription. Thus, "lethal mutagenesis" driven by the class of deoxynucleoside analogs represented by 5-OH-dC could provide a new approach to treating HIV infections and, potentially, other viral infections. PMID- 9990052 TI - The [URE3] prion is an aggregated form of Ure2p that can be cured by overexpression of Ure2p fragments. AB - The [URE3] nonchromosomal genetic element is a prion of Ure2p, a regulator of nitrogen catabolism in Saccharomyces cerevisiae. Ure2p1-65 is the prion domain of Ure2p, sufficient to propagate [URE3] in vivo. We show that full length Ure2p green fluorescent protein (GFP) or a Ure2p1-65-GFP fusion protein is aggregated in cells carrying [URE3] but is evenly distributed in cells lacking the [URE3] prion. This indicates that [URE3] involves a self-propagating aggregation of Ure2p. Overexpression of Ure2p1-65 induces the de novo appearance of [URE3] by 1,000-fold in a strain initially [ure-o], but cures [URE3] from a strain initially carrying the [URE3] prion. Overexpression of several other fragments of Ure2p or Ure2-GFP fusion proteins also efficiently cures the prion. We suggest that incorporation of fragments or fusion proteins into a putative [URE3] "crystal" of Ure2p poisons its propagation. PMID- 9990053 TI - Triplet repeats form secondary structures that escape DNA repair in yeast. AB - Several human neurodegenerative diseases result from expansion of CTG/CAG or CGG/CCG triplet repeats. The finding that single-stranded CNG repeats form hairpin-like structures in vitro has led to the hypothesis that DNA secondary structure formation is an important component of the expansion mechanism. We show that single-stranded DNA loops containing 10 CTG/CAG or CGG/CCG repeats are inefficiently repaired during meiotic recombination in Saccharomyces cerevisiae. Comparisons of the repair of DNA loops with palindromic and nonpalindromic sequences suggest that this inefficient repair reflects the ability of these sequences to form hairpin structures in vivo. PMID- 9990054 TI - The identification of markers segregating with resistance to Schistosoma mansoni infection in the snail Biomphalaria glabrata. AB - Both snail and parasite genes determine the susceptibility of the snail Biomphalaria glabrata to infection with the trematode Schistosoma mansoni. To identify molecular markers associated with resistance to the parasite in the snail host, we performed genetic crosses between parasite-resistant and susceptible isogenic snails. Because resistance to infection in adult snails is controlled by a single locus, DNA samples from individual F2 and F1 backcross progeny, segregating for either the resistant or susceptible phenotypes, were pooled (bulked segregant). Genotypes for both parents were determined with 205 arbitrary decamer primers by random amplified polymorphic DNA-PCR. Of the 205 primers, 144 were informative, and the relative allele frequencies between the pools for these primers were determined. Two primers, OPM-04 and OPZ-11, produced fragments in the resistant parent of one cross that were inherited in a dominant fashion in the resistant F2 and backcross-bulked segregant progeny. Subsequent typing of DNA samples of individual progeny snails showed that the 1.2-kb marker amplified by primer OPM-04 and the 1.0-kb marker produced by primer OPZ-11 segregated in the same dominant fashion with the resistant phenotype. Sequence analysis of the 1.2-kb marker showed that it corresponds to a repetitive sequence in the snail genome with no homology to existing DNA sequences in the public databases. Analysis of the 1. 0-kb marker showed that it also corresponds to a repetitive sequence in the B. glabrata genome that contains an imperfect ORF, with homology to retrovirus-related group-specific antigens (gag) polyprotein. PMID- 9990055 TI - Trapping cDNAs encoding secreted proteins from the salivary glands of the malaria vector Anopheles gambiae. AB - The signal sequence trap method was used to isolate cDNAs corresponding to proteins containing secretory leader peptides and whose genes are expressed specifically in the salivary glands of the malaria vector Anopheles gambiae. Fifteen unique cDNA fragments, ranging in size from 150 to 550 bp, were isolated and sequenced in a first round of immunoscreening in COS-7 cells. All but one of the cDNAs contained putative signal sequences at their 5' ends, suggesting that they were likely to encode secreted or transmembrane proteins. Expression analysis by reverse transcription-PCR showed that at least six cDNA fragments were expressed specifically in the salivary glands. Fragments showing a high degree of similarity to D7 and apyrase, two salivary gland-specific genes previously found in Aedes aegypti, were identified. Of interest, three different D7-related cDNAs that are likely to represent a new gene family were found in An. gambiae. Moreover, three salivary gland-specific cDNA fragments that do not show similarity to known proteins in the databases were identified, and the corresponding full length cDNAs were cloned and sequenced. RNA in situ hybridization to whole female salivary glands showed patterns of expression that overlap only in part those observed in the culicine mosquito A. aegypti. PMID- 9990056 TI - Odortypes: their origin and composition. AB - Odors that distinguish one individual from another member of the species and are determined by polymorphic genes are called odortypes. Odortypes and their considerable societal significance have been studied intimately only in mice and mainly with respect to the genes of the major histocompatibility complex. Further understanding and the matter of human relevance have been hampered by the apparent restriction of odortype expression to urine. The present finding that odorants comprising prerenal odortypes are already present in blood, albeit in masked form, affords the basis of a comprehensive view of odortypes. Accordingly, major histocompatibility complex and other polymorphic genes of antiquity are seen inter alia as agents of normal variation, which entails quantitative variation in output of odorant metabolites. Relatively few such normal variations should suffice for a vast range of compound odors whose specificity is determined by combinative assortment of the same set of individual volatile compounds. PMID- 9990057 TI - Recombination and transcription of the endogenous Ig heavy chain locus is effected by the Ig heavy chain intronic enhancer core region in the absence of the matrix attachment regions. AB - The intronic Ig heavy chain (IgH) enhancer, which consists of the core enhancer flanked by 5' and 3' matrix attachment regions, has been implicated in control of IgH locus recombination and transcription. To elucidate the regulatory functions of the core enhancer and its associated matrix attachment regions in the endogenous IgH locus, we have introduced targeted deletions of these elements, both individually and in combination, into an IgHa/b-heterozygous embryonic stem cell line. These embryonic stem cells were used to generate chimeric mice by recombination activating gene-2 (Rag-2)-deficient blastocyst complementation, and the effects of the introduced mutations were assayed in mutant B cells. We find that the core enhancer is necessary and sufficient to promote normal variable (V), diversity (D), and joining (J) segment recombination in developing B lineage cells and IgH locus transcription in mature B cells. Surprisingly, the 5' and 3' matrix attachment regions were dispensable for these processes. PMID- 9990058 TI - Immune regulatory loops determine productive interactions within human T lymphocyte-dendritic cell clusters. AB - Help for the induction of cytolytic T lymphocytes is mediated by dendritic cells (DC) that are conditioned by CD40 signaling. We identified tumor necrosis factor family member CD27L/CD70, which is expressed by cytolytic T lymphocytes on interaction with DC to control CD154 (CD40L) up-regulation on CD45RA+ helper T cells for subsequent DC stimulation. The results show that the initiation of a cytolytic immune response is determined by regulatory circuits, requiring simultaneous activation and differentiation of all cells involved in T lymphocyte DC cluster formation. PMID- 9990059 TI - T cell receptor gene deletion circles identify recent thymic emigrants in the peripheral T cell pool. AB - Progenitor cells undergo T cell receptor (TCR) gene rearrangements during their intrathymic differentiation to become T cells. Rearrangements of the variable (V), diversity (D), and joining (J) segments of the TCR genes result in deletion of the intervening chromosomal DNA and the formation of circular episomes as a byproduct. Detection of these extrachromosomal excision circles in T cells located in the peripheral lymphoid tissues has been viewed as evidence for the existence of extrathymic T cell generation. Because all of the T cells in chickens apparently are generated in the thymus, we have employed this avian model to determine the fate of the V(D)J deletion circles. In normal animals we identified TCR Vgamma-Jgamma and Vbeta-Dbeta deletion circles in the blood, spleen, and intestines, as well as in the thymus. Thymectomy resulted in the gradual loss of these DNA deletion circles in all of the peripheral lymphoid tissues. A quantitative PCR analysis of Vgamma1-Jgamma1 and Vbeta1-Dbeta deletion circles in splenic gamma delta and Vbeta1(+) alphabeta T cells indicated that their numbers progressively decline after thymectomy with a half-life of approximately 2 weeks. Although TCR deletion circles therefore cannot be regarded as reliable indicators of in situ V(D)J rearrangement, measuring their levels in peripheral T cell samples can provide a valuable index of newly generated T cells entering the T cell pool. PMID- 9990060 TI - GA-binding protein factors, in concert with the coactivator CREB binding protein/p300, control the induction of the interleukin 16 promoter in T lymphocytes. AB - Interleukin 16 (IL-16) is a chemotactic cytokine that binds to the CD4 receptor and affects the activation of T cells and replication of HIV. It is expressed as a large 67-kDa precursor protein (pro-IL-16) in lymphocytes, macrophages, and mast cells, as well as in airway epithelial cells from asthmatics after challenge with allergen. This pro-IL-16 is subsequently processed to the mature cytokine of 13 kDa. To study the expression of IL-16 at the transcriptional level, we cloned the human chromosomal IL-16 gene and analyzed its promoter. The human IL-16 gene consists of seven exons and six introns. The 5' sequences up to nucleotide -120 of the human and murine IL-16 genes share >84% sequence homology and harbor promoter elements for constitutive and inducible transcription in T cells. Although both promoters lack any TATA box, they contain two CAAT box-like motifs and three binding sites of GA-binding protein (GABP) transcription factors. Two of these motifs are part of a highly conserved and inducible dyad symmetry element shown previously to control a remote IL-2 enhancer and the CD18 promoter. In concert with the coactivator CREB binding protein/p300, which interacts with GABPalpha, the binding of GABPalpha and -beta to the dyad symmetry element controls the induction of IL-16 promoter in T cells. Supplementing the data on the processing of pro-IL-16, our results indicate the complexity of IL-16 expression, which is tightly controlled at the transcriptional and posttranslational levels in T lymphocytes. PMID- 9990061 TI - Multivalent structure of an alphabetaT cell receptor. AB - Whether there is one or multiple alphabetaT cell antigen receptor (TCR) recognition modules in a given TCR/CD3 complex is a long-standing controversy in immunology. We show that T cells from transgenic mice that coexpress comparable amounts of two distinct TCRbeta chains incorporate at least two alphabetaTCRs in a single TCR/CD3 complex. Evidence for bispecific alphabetaTCRs was obtained by immunoprecipitation and immunoblotting and confirmed on the surface of living cells both by fluorescence resonance energy transfer and comodulation assays by using antibodies specific for TCRbeta-variable regions. Such (alphabeta)2TCR/CD3 or higher-order complexes were evident in T cells studied either ex vivo or after expansion in vitro. T cell activation is thought by many, but not all, to require TCR cross-linking by its antigen/major histocompatibility complex ligand. The implications of a multivalent (alphabeta)2TCR/CD3 complex stoichiometry for the ordered docking of specific antigen/major histocompatibility complex, CD4, or CD8 coreceptors and additional TCRs are discussed. PMID- 9990062 TI - A gene therapy for cancer using intramuscular injection of plasmid DNA encoding interferon alpha. AB - A cancer treatment is described in which i.m. injection of plasmid DNA (pDNA) encoding murine interferon alpha (mIFN-alpha) leads to potent antitumor effects on primary and metastatic tumors in mice. Mice bearing s.c. B16F10 melanoma, Cloudman melanoma, or glioma 261 tumors were injected i.m. with mIFN-alpha pDNA. In all three tumor models, a significant reduction in tumor volume and enhancement of survival was found after IFN pDNA therapy. The mIFN-alpha pDNA could be injected as infrequently as once every other week and still produce a significant antitumor effect, and, in a metastatic tumor model, the therapy markedly reduced the number of lung tumor metastases. Depletion of immune cell subsets indicated that CD8(+) T cells were required for the antitumor response. These studies demonstrate that primary and metastatic tumors can be treated systemically by i.m. injection of a plasmid encoding a cytokine gene. PMID- 9990063 TI - On the mechanism by which vascular endothelial cells regulate their oxygen consumption. AB - Two enzymes, soluble guanylyl cyclase and cytochrome c oxidase, have been shown to be exquisitely sensitive to nitric oxide (NO) at low physiological concentrations. Activation of the soluble guanylyl cyclase by endogenous NO and the consequent increase in the second messenger cyclic GMP are now known to control a variety of biological functions. Cytochrome c oxidase, the terminal enzyme of the mitochondrial respiratory chain, is inhibited by NO. However, it is not clear whether NO produced by the constitutive NO synthase interacts with cytochrome c oxidase, nor is it known what the biological consequences of such an interaction might be. We now show that NO generated by vascular endothelial cells under basal and stimulated conditions modulates the respiration of these cells in response to acute changes in oxygen concentration. This action occurs at the cytochrome c oxidase and depends on influx of calcium. Thus, NO plays a physiological role in adjusting the capacity of this enzyme to use oxygen, allowing endothelial cells to adapt to acute changes in their environment. PMID- 9990064 TI - Mutation of Pten/Mmac1 in mice causes neoplasia in multiple organ systems. AB - Pten/Mmac1+/- heterozygous mice exhibited neoplasms in multiple organs including the endometrium, liver, prostate, gastrointestinal tract, thyroid, and thymus. Loss of the wild-type allele was detected in neoplasms of the thymus and liver. Surprisingly, tumors of the gastrointestinal epithelium developed in association with gut lymphoid tissue. Tumors of the endometrium, thyroid, prostate, and liver were not associated with lymphoid tissue and appeared to be highly mitotic. In addition, these mice have nonneoplastic hyperplasia of lymph nodes that was caused by an inherited defect in apoptosis detected in B cells and macrophages. Examination of peripheral lymphoid tissue including lymphoid aggregates associated with polyps revealed that the normal organization of B and T cells was disrupted in heterozygous animals. Taken together, these data suggest that PTEN is a regulator of apoptosis and proliferation that behaves as a "landscaper" tumor suppressor in the gut and a "gatekeeper" tumor suppressor in other organs. PMID- 9990065 TI - Prototypic G protein-coupled receptor for the intestinotrophic factor glucagon like peptide 2. AB - Glucagon-like peptide 2 (GLP-2) is a 33-aa proglucagon-derived peptide produced by intestinal enteroendocrine cells. GLP-2 stimulates intestinal growth and up regulates villus height in the small intestine, concomitant with increased crypt cell proliferation and decreased enterocyte apoptosis. Moreover, GLP-2 prevents intestinal hypoplasia resulting from total parenteral nutrition. However, the mechanism underlying these actions has remained unclear. Here we report the cloning and characterization of cDNAs encoding rat and human GLP-2 receptors (GLP 2R), a G protein-coupled receptor superfamily member expressed in the gut and closely related to the glucagon and GLP-1 receptors. The human GLP-2R gene maps to chromosome 17p13.3. Cells expressing the GLP-2R responded to GLP-2, but not GLP-1 or related peptides, with increased cAMP production (EC50 = 0.58 nM) and displayed saturable high-affinity radioligand binding (Kd = 0.57 nM), which could be displaced by synthetic rat GLP-2 (Ki = 0.06 nM). GLP-2 analogs that activated GLP-2R signal transduction in vitro displayed intestinotrophic activity in vivo. These results strongly suggest that GLP-2, like glucagon and GLP-1, exerts its actions through a distinct and specific novel receptor expressed in its principal target tissue, the gastrointestinal tract. PMID- 9990066 TI - Multinuclear solid-state three-dimensional MRI of bone and synthetic calcium phosphates. AB - Multinuclear three-dimensional solid-state MRI of bone, tooth, and synthetic calcium phosphates is demonstrated in vitro and in vivo with a projection reconstruction technique based on acquisition of free induction decays in the presence of fixed amplitude magnetic field gradients. Phosphorus-31 solid-state MRI provides direct images of the calcium phosphate constituents of bone substance and is a quantitative measurement of the true volumetric bone mineral density of the bone. Proton solid-state MRI shows the density of bone matrix including its organic constituents, which consist principally of collagen. These solid-state MRI methods promise to yield a biological picture of bone richer in information concerning the bone composition and short range-crystalline order than the fluid-state images provided by conventional proton MRI or the density images produced by radiologic imaging techniques. Three-dimensional solid-state projection reconstruction MRI should be readily adaptable to both human clinical use and nonmedical applications for a variety of solids in materials science. PMID- 9990067 TI - Association of HFE protein with transferrin receptor in crypt enterocytes of human duodenum. AB - In hereditary hemochromatosis (HH), intestinal absorption of dietary iron is increased, leading to excessive iron accumulation in tissues and resultant organ damage. The HFE protein, which is defective in HH, normally is expressed in crypt enterocytes of the duodenum where it has a unique, predominantly intracellular localization. In placenta, the HFE protein colocalizes with and forms a stable association with the transferrin receptor (TfR), providing a link between the HFE protein and iron transport. In the present study, we examined the relationship of the HFE protein to the TfR in enterocytes of the human duodenum and measured the uptake of transferrin-bound iron and ionic iron by isolated crypt and villus enterocytes. Immunocytochemistry showed that the HFE protein and TfR both are expressed in the crypt enterocytes. Western blots showed that, as was the case in human placenta, the HFE protein in crypt enterocytes is physically associated with the TfR and with beta2-microglobulin. The crypt cell fraction exhibited dramatically higher transferrin-bound iron uptake than villus cells. On the other hand, the villus cells showed 2-3 times higher uptake of ionic iron than crypt cells. We propose that the HFE protein modulates the uptake of transferrin-bound iron from plasma by crypt enterocytes and participates in the mechanism by which the crypt enterocytes sense the level of body iron stores. Impairment of this function caused by HFE gene mutations in HH could provide a paradoxical signal in crypt enterocytes that programs the differentiating enterocytes to absorb more dietary iron when they mature into villus enterocytes. PMID- 9990068 TI - Mouse steroid receptor coactivator-1 is not essential for peroxisome proliferator activated receptor alpha-regulated gene expression. AB - Peroxisome proliferator-activated receptors (PPARs) are ligand-dependent transcription factors, and it is assumed that the biological effects of these receptors depend on interactions with recently identified coactivators, including steroid receptor coactivator-1 (SRC-1). We assessed the in vivo function of SRC-1 on the PPARalpha-regulated gene expression in liver by generating mice in which the SRC-1 gene was inactivated by gene targeting. The homozygous (SRC-1(-/-)) mice were viable and fertile and exhibited no detectable gross phenotypic defects. When challenged with a PPARalpha ligand, such as ciprofibrate or Wy 14,643, the SRC-1(-/-) mice displayed typical pleiotropic responses, including hepatomegaly, peroxisome proliferation in hepatocytes, and increased mRNA and protein levels of genes that are regulated by PPARalpha. These alterations were indistinguishable from those exhibited by SRC-1(+/+) wild-type mice fed either ciprofibrate- or Wy-14, 643-containing diets. These results indicate that SRC-1 is not essential for PPARalpha-mediated transcriptional activation in vivo and suggest redundancy in nuclear receptor coactivators. PMID- 9990069 TI - Synergy between an antiangiogenic integrin alphav antagonist and an antibody cytokine fusion protein eradicates spontaneous tumor metastases. AB - The suppression and eradication of primary tumors and distant metastases is a major goal of alternative treatment strategies for cancer, such as inhibition of angiogenesis and targeted immunotherapy. We report here a synergy between two novel monotherapies directed against vascular and tumor compartments, respectively, a tumor vasculature-specific antiangiogenic integrin alphav antagonist and tumor-specific antibody-interleukin 2 (IL-2) fusion proteins. Simultaneous and sequential combination of these monotherapies effectively eradicated spontaneous liver metastases in a poorly immunogenic syngeneic model of neuroblastoma. This was in contrast to controls subjected to monotherapies with either an antiangiogenic integrin alphav antagonist or antibody-IL-2 fusion proteins, which were only partially effective at the dose levels applied. Furthermore, simultaneous treatments with the integrin alphav antagonist and tumor-specific antibody-IL-2 fusion proteins induced dramatic primary tumor regressions in three syngeneic murine tumor models, i.e., melanoma, colon carcinoma, and neuroblastoma. However, each agent used as monotherapy induced only a delay in tumor growth. A mechanism for this synergism was suggested because the antitumor response was accompanied by a simultaneous 50% reduction in tumor vessel density and a 5-fold increase in inflammatory cells in the tumor microenvironment. Subsequently, tumor necrosis was demonstrated only in animals receiving the combination therapy, but not when each agent was applied as monotherapy. The results suggest that these synergistic treatment modalities may provide a novel and effective tool for future therapies of metastatic cancer. PMID- 9990070 TI - Regulation of selectin binding activity by cyclization of sialic acid moiety of carbohydrate ligands on human leukocytes. AB - We provide here evidence that supports the occurrence of a biologically dormant form of selectin ligand carbohydrate, the sialyl 6-sulfo Lewis X containing modified sialic acid, in human leukocytes. The modification of sialic acid involves first de-N-acetylation of sialic acid moiety through ubiquitous de-N acetylation/re-N-acetylation cycle, followed by the dehydrative cyclization of de N-acetyl sialic acid to form "cyclic sialic acid." The enzyme involved in the dehydration of de-N-acetyl sialic acid is a calcium-dependent enzyme having neutral-alkaline pH optimum. De-N-acetyl sialyl 6-sulfo Lewis X retained selectin binding activity as well as parental sialyl 6-sulfo Lewis X, but cyclic sialyl 6 sulfo Lewis X was devoid of selectin binding activity. Sialyl 6-sulfo Lewis X carrying the cyclic sialic acid is specifically recognized by the newly generated mAb, G159. The determinant was distributed widely among normal human leukocytes, especially on monocytes and subsets of lymphocytes including NK cells, helper memory T cells, Tcr-gammadelta T cells, and a part of B cells. The determinant was detected also on several cultured lymphocytic leukemia cell lines and O tetradecanoylphorbol 13-acetate-activated lymphoid cells. Cyclic sialyl 6-sulfo Lewis X is efficiently formed by the action of the partly membrane-bound calcium dependent enzyme, tentatively called "sialic acid cyclase," and a possible physiological significance of this reaction could be a rapid inactivation of selectin binding activity at the cell surface. Conversely, the accumulated intracellular cyclic sialyl 6-sulfo Lewis X determinant may function as a dormant pool of selectin ligands, which, on appropriate stimulation, is hydrolyzed and becomes active in selectin-dependent cell adhesion. PMID- 9990071 TI - Target genes of beta-catenin-T cell-factor/lymphoid-enhancer-factor signaling in human colorectal carcinomas. AB - Mutations in the adenomatous polyposis coli or beta-catenin gene lead to cytosolic accumulation of beta-catenin and, subsequently, to increased transcriptional activity of the beta-catenin-T cell-factor/lymphoid-enhancer factor complex. This process seems to play an essential role in the development of most colorectal carcinomas. To identify genes activated by beta-catenin overexpression, we used colorectal cell lines for transfection with the beta catenin gene and searched for genes differentially expressed in the transfectants. There are four genes affected by beta-catenin overexpression; three overexpressed genes code for two components of the AP-1 transcription complex, c-jun and fra-1, and for the urokinase-type plasminogen activator receptor (uPAR), whose transcription is activated by AP-1. The direct interaction of the beta-catenin-T cell-factor/lymphoid-enhancer-factor complex with the promoter region of c-jun and fra-1 was shown in a gel shift assay. The concomitant increase in beta-catenin expression and the amount of uPAR was confirmed in primary colon carcinomas and their liver metastases at both the mRNA and the protein levels. High expression of beta-catenin in transfectants, as well as in additionally analyzed colorectal cell lines, was associated with decreased expression of ZO-1, which is involved in epithelial polarization. Thus, accumulation of beta-catenin indirectly affects the expression of uPAR in vitro and in vivo. Together with the other alterations, beta-catenin accumulation may contribute to the development and progression of colon carcinoma both by dedifferentiation and through proteolytic activity. PMID- 9990072 TI - Activating and dominant inactivating c-KIT catalytic domain mutations in distinct clinical forms of human mastocytosis. AB - Human mastocytosis is characterized by increased mast cells. It usually occurs as a sporadic disease that is often transient and limited in children and persistent or progressive in adults. The c-KIT protooncogene encodes KIT, a tyrosine kinase that is the receptor for mast cell growth factor. Because mutated KIT can transform cells, we examined c-KIT in skin lesions of 22 patients with sporadic mastocytosis and 3 patients with familial mastocytosis. All patients with adult sporadic mastocytosis had somatic c-KIT mutations in codon 816 causing substitution of valine for aspartate and spontaneous activation of mast cell growth factor receptor (P = 0.0001). A subset of four pediatric onset cases with clinically unusual disease also had codon 816 activating mutations substituting valine, tyrosine, or phenylalanine for aspartate. Typical pediatric patients lacked 816 mutations, but limited sequencing showed three of six had a novel dominant inactivating mutation substituting lysine for glutamic acid in position 839, the site of a potential salt bridge that is highly conserved in receptor tyrosine kinases. No c-KIT mutations were found in the entire coding region of three patients with familial mastocytosis. We conclude that c-KIT somatic mutations substituting valine in position 816 of KIT are characteristic of sporadic adult mastocytosis and may cause this disease. Similar mutations causing activation of the mast cell growth factor receptor are found in children apparently at risk for extensive or persistent disease. In contrast, typical pediatric mastocytosis patients lack these mutations and may express inactivating c-KIT mutations. Familial mastocytosis, however, may occur in the absence of c KIT coding mutations. PMID- 9990073 TI - Immunogenicity and in vitro protective efficacy of a recombinant multistage Plasmodium falciparum candidate vaccine. AB - Compared with a single-stage antigen-based vaccine, a multistage and multivalent Plasmodium falciparum vaccine would be more efficacious by inducing "multiple layers" of immunity. We have constructed a synthetic gene that encodes for 12 B cell, 6 T cell proliferative, and 3 cytotoxic T lymphocyte epitopes derived from 9 stage-specific P. falciparum antigens corresponding to the sporozoite, liver, erythrocytic asexual, and sexual stages. The gene was expressed in the baculovirus system, and a 41-kDa antigen, termed CDC/NIIMALVAC-1, was purified. Immunization in rabbits with the purified protein in the presence of different adjuvants generated antibody responses that recognized vaccine antigen, linear peptides contained in the vaccine, and all stages of P. falciparum. In vitro assays of protection revealed that the vaccine-elicited antibodies strongly inhibited sporozoite invasion of hepatoma cells and growth of blood-stage parasites in the presence of monocytes. These observations demonstrate that a multicomponent, multistage malaria vaccine can induce immune responses that inhibit parasite development at multiple stages. The rationale and approach used in the development of a multicomponent P. falciparum vaccine will be useful in the development of a multispecies human malaria vaccine and vaccines against other infectious diseases. PMID- 9990074 TI - Allelic association between marker loci. AB - Allelic association has proven useful to refine the location of major genes prior to positional cloning, but it is of uncertain value for genome scans in complex inheritance. We have extended kinship theory to give information content for linkage and allelic association. Application to pairs of closely linked markers as a surrogate for marker x oligogene pairs indicates that association is largely determined by regional founders, with little effect of subsequent demography. Sub Saharan Africa has the least allelic association, consistent with settlement of other regions by small numbers of founders. Recent speculation about substantial advantages of isolates over large populations, of constant size over expansion, and of F1 hybrids over incrosses is not supported by theory or data. On the contrary, fewer affected cases, less opportunity for replication, and more stochastic variation tend to make isolates less informative for allelic association, as they are for linkage. PMID- 9990075 TI - Human single-chain Fv immunoconjugates targeted to a melanoma-associated chondroitin sulfate proteoglycan mediate specific lysis of human melanoma cells by natural killer cells and complement. AB - Two antimelanoma immunoconjugates containing a human single-chain Fv (scFv) targeting domain conjugated to the Fc effector domain of human IgG1 were synthesized as secreted two-chain molecules in Chinese hamster ovary and Drosophila S2 cells, and purified by affinity chromatography on protein A. The scFv targeting domains originally were isolated as melanoma-specific clones from a scFv fusion-phage library, derived from the antibody repertoire of a vaccinated melanoma patient. The purified immunoconjugates showed similar binding specificity as did the fusion-phage clones. Binding occurred to human melanoma cells but not to human melanocytes or to several other types of normal cells and tumor cells. A 250-kDa melanoma protein was immunoprecipitated by the immunoconjugates and analyzed by mass spectrometry, using two independent procedures. A screen of protein sequence databases showed an exact match of several peptide masses between the immunoprecipitated protein and the core protein of a chondroitin sulfate proteoglycan, which is expressed on the surface of most human melanoma cells. The Fc effector domain of the immunoconjugates binds natural killer (NK) cells and also the C1q protein that initiates the complement cascade; both NK cells and complement can activate powerful cytolytic responses against the targeted tumor cells. An in vitro cytolysis assay was used to test for an immunoconjugate-dependent specific cytolytic response against cultured human melanoma cells by NK cells and complement. The melanoma cells, but not the human fibroblast cells used as the control, were efficiently lysed by both NK cells and complement in the presence of the immunoconjugates. The in vitro results suggest that the immunoconjugates also could activate a specific cytolytic immune response against melanoma tumors in vivo. PMID- 9990076 TI - Epiregulin is a potent vascular smooth muscle cell-derived mitogen induced by angiotensin II, endothelin-1, and thrombin. AB - Vasoactive GTP-binding protein-coupled receptor agonists such as angiotensin II (AII), endothelin-1 (ET-1), and alpha-thrombin (alpha-Thr) have been reported to indirectly stimulate vascular smooth muscle cell (VSMC) proliferation by regulating the expression of one or more autocrine growth factors. Using ion exchange, gel-filtration, and reverse-phase chromatographic purification methods, we isolated a major mitogenic protein present in AII-stimulated rat aortic smooth muscle (RASM) cell conditioned medium. Twenty N-terminal amino acids of the purified peptide were identified, and they had 75% amino acid sequence identity with mouse epiregulin, an epidermal growth factor (EGF)-related growth factor. We cloned the cDNA for rat epiregulin to determine its pattern of expression in G protein-coupled receptor agonist-stimulated cells and confirm its activity as a mitogen. After treatment of RASM cells with AII, ET-1, or alpha-Thr for 1 h, induction of two epiregulin transcripts was observed, including a 4.8-kb transcript and a novel transcript of approximately 1.2 kb. Recombinant rat epiregulin was strongly mitogenic for RASM cells, stimulating DNA synthesis to levels similar to those induced by serum or platelet-derived growth factor and approximately 3-fold above that observed with saturating concentrations of EGF. In addition, epiregulin caused rapid EGF receptor activation in RASM cells. However, relative levels of EGF receptor tyrosine phosphorylation stimulated by epiregulin were less than those induced by EGF or betacellulin. Taken together, these results indicate that epiregulin is a potent VSMC-secreted mitogen, induced in common by AII, ET-1, and alpha-Thr, that may contribute to VSMC proliferation and vascular remodeling stimulated by vasoactive agonists. PMID- 9990077 TI - Quorum sensing in Escherichia coli, Salmonella typhimurium, and Vibrio harveyi: a new family of genes responsible for autoinducer production. AB - In bacteria, the regulation of gene expression in response to changes in cell density is called quorum sensing. Quorum-sensing bacteria produce, release, and respond to hormone-like molecules (autoinducers) that accumulate in the external environment as the cell population grows. In the marine bacterium Vibrio harveyi two parallel quorum-sensing systems exist, and each is composed of a sensor autoinducer pair. V. harveyi reporter strains capable of detecting only autoinducer 1 (AI-1) or autoinducer 2 (AI-2) have been constructed and used to show that many species of bacteria, including Escherichia coli MG1655, E. coli O157:H7, Salmonella typhimurium 14028, and S. typhimurium LT2 produce autoinducers similar or identical to the V. harveyi system 2 autoinducer AI-2. However, the domesticated laboratory strain E. coli DH5alpha does not produce this signal molecule. Here we report the identification and analysis of the gene responsible for AI-2 production in V. harveyi, S. typhimurium, and E. coli. The genes, which we have named luxSV.h., luxSS.t., and luxSE.c. respectively, are highly homologous to one another but not to any other identified gene. E. coli DH5alpha can be complemented to AI-2 production by the introduction of the luxS gene from V. harveyi or E. coli O157:H7. Analysis of the E. coli DH5alpha luxSE.c. gene shows that it contains a frameshift mutation resulting in premature truncation of the LuxSE.c. protein. Our results indicate that the luxS genes define a new family of autoinducer-production genes. PMID- 9990078 TI - In vivo transposition of mariner-based elements in enteric bacteria and mycobacteria. AB - mariner family transposons are widespread among eukaryotic organisms. These transposons are apparently horizontally transmitted among diverse eukaryotes and can also transpose in vitro in the absence of added cofactors. Here we show that transposons derived from the mariner element Himar1 can efficiently transpose in bacteria in vivo. We have developed simple transposition systems by using minitransposons, made up of short inverted repeats flanking antibiotic resistance markers. These elements can efficiently transpose after expression of transposase from an appropriate bacterial promoter. We found that transposition of mariner based elements in Escherichia coli produces diverse insertion mutations in either a targeted plasmid or a chromosomal gene. With Himar1-derived transposons we were able to isolate phage-resistant mutants of both E. coli and Mycobacterium smegmatis. mariner-based transposons will provide valuable tools for mutagenesis and genetic manipulation of bacteria that currently lack well developed genetic systems. PMID- 9990079 TI - Origin and evolution of the 1918 "Spanish" influenza virus hemagglutinin gene. AB - The "Spanish" influenza pandemic killed over 20 million people in 1918 and 1919, making it the worst infectious pandemic in history. Here, we report the complete sequence of the hemagglutinin (HA) gene of the 1918 virus. Influenza RNA for the analysis was isolated from a formalin-fixed, paraffin-embedded lung tissue sample prepared during the autopsy of a victim of the influenza pandemic in 1918. Influenza RNA was also isolated from lung tissue samples from two additional victims of the lethal 1918 influenza: one formalin-fixed, paraffin-embedded sample and one frozen sample obtained by in situ biopsy of the lung of a victim buried in permafrost since 1918. The complete coding sequence of the A/South Carolina/1/18 HA gene was obtained. The HA1 domain sequence was confirmed by using the two additional isolates (A/New York/1/18 and A/Brevig Mission/1/18). The sequences show little variation. Phylogenetic analyses suggest that the 1918 virus HA gene, although more closely related to avian strains than any other mammalian sequence, is mammalian and may have been adapting in humans before 1918. PMID- 9990080 TI - Localization of Niemann-Pick C1 protein in astrocytes: implications for neuronal degeneration in Niemann- Pick type C disease. AB - Niemann-Pick type C disease (NP-C) is an inherited neurovisceral lipid storage disorder characterized by progressive neurodegeneration. Most cases of NP-C result from inactivating mutations of NPC1, a recently identified member of a family of genes encoding membrane-bound proteins containing putative sterol sensing domains. By using a specific antipeptide antibody to human NPC1, we have here investigated the cellular and subcellular localization and regulation of NPC1. By light and electron microscopic immunocytochemistry of monkey brain, NPC1 was expressed predominantly in perisynaptic astrocytic glial processes. At a subcellular level, NPC1 localized to vesicles with the morphological characteristics of lysosomes and to sites near the plasma membrane. Analysis of the temporal and spatial pattern of neurodegeneration in the NP-C mouse, a spontaneous mutant model of human NP-C, by amino-cupric-silver staining, showed that the terminal fields of axons and dendrites are the earliest sites of degeneration that occur well before the appearance of a neurological phenotype. Western blots of cultured human fibroblasts and monkey brain homogenates revealed NPC1 as a 165-kDa protein. NPC1 levels in cultured fibroblasts were unchanged by incubation with low density lipoproteins or oxysterols but were increased 2- to 3 fold by the drugs progesterone and U-18666A, which block cholesterol transport out of lysosomes, and by the lysosomotropic agent NH4Cl. These studies show that NPC1 in brain is predominantly a glial protein present in astrocytic processes closely associated with nerve terminals, the earliest site of degeneration in NP C. Given the vesicular localization of NPC1 and its proposed role in mediating retroendocytic trafficking of cholesterol and other lysosomal cargo, these results suggest that disruption of NPC1-mediated vesicular trafficking in astrocytes may be linked to neuronal degeneration in NP-C. PMID- 9990081 TI - Functional MRI reveals spatially specific attentional modulation in human primary visual cortex. AB - Selective visual attention can strongly influence perceptual processing, even for apparently low-level visual stimuli. Although it is largely accepted that attention modulates neural activity in extrastriate visual cortex, the extent to which attention operates in the first cortical stage, striate visual cortex (area V1), remains controversial. Here, functional MRI was used at high field strength (3 T) to study humans during attentionally demanding visual discriminations. Similar, robust attentional modulations were observed in both striate and extrastriate cortical areas. Functional mapping of cortical retinotopy demonstrates that attentional modulations were spatially specific, enhancing responses to attended stimuli and suppressing responses when attention was directed elsewhere. The spatial pattern of modulation reveals a complex attentional window that is consistent with object-based attention but is inconsistent with a simple attentional spotlight. These data suggest that neural processing in V1 is not governed simply by sensory stimulation, but, like extrastriate regions, V1 can be strongly and specifically influenced by attention. PMID- 9990082 TI - Covariation of activity in visual and prefrontal cortex associated with subjective visual perception. AB - Visual areas of the occipitotemporal pathway are thought to be essential for the conscious perception of objects, but the contribution of other cortical regions and the neural mechanisms leading to the awareness of a visual stimulus remain unclear. By using functional MRI in humans exposed to bistable viewing conditions, subjective visual perception was related to covariation of activity in multiple extrastriate ventral, parietal, and prefrontal cortical areas. The coordination of activity among these regions was not linked to external sensory or motor events; rather, it reflected internal changes in perception and varied in strength with the frequency of perceptual events, suggesting that functional interactions between visual and prefrontal cortex may contribute to conscious vision. Because similar cortical systems have been implicated in short-term memory and motor planning, the results also imply that related neural processes may underlie visual awareness and the organization of voluntary behavior contingent on sensory cues. PMID- 9990083 TI - Dynamics of tremor-related oscillations in the human globus pallidus: a single case study. AB - Physiological evidence indicates that the resting tremor of Parkinson's disease originates in oscillatory neural activity in the forebrain, but it is unknown whether that activity is globally synchronized or consists of parallel, independently oscillating circuits. In the present study, we used dual microelectrodes to record tremor-related neuronal activity from eight sites in the internal segment of the globus pallidus (GPi) from an awake Parkinson's disease patient undergoing stereotaxic pallidotomy. We utilized spectral analysis to evaluate the temporal correlations between multiunit activity at spatially separated sites and between neural and limb electromyographic activity. We observed that some GPi neural pairs oscillated synchronously at the tremor frequency, whereas other neural pairs oscillated independently. Additionally, we found that GPi tremor-related activity at a given site could fluctuate between states of synchronization and independence with respect to upper limb tremor. Consistent with this finding, some paired recording sites within GPi showed periods of transient synchronization. These observations support the hypothesis of independent tremor-generating circuits whose coupling can fluctuate over time. PMID- 9990084 TI - A subcortical pathway to the right amygdala mediating "unseen" fear. AB - Neuroimaging studies have shown differential amygdala responses to masked ("unseen") emotional stimuli. How visual signals related to such unseen stimuli access the amygdala is unknown. A possible pathway, involving the superior colliculus and pulvinar, is suggested by observations of patients with striate cortex lesions who show preserved abilities to localize and discriminate visual stimuli that are not consciously perceived ("blindsight"). We used measures of right amygdala neural activity acquired from volunteer subjects viewing masked fear-conditioned faces to determine whether a colliculo-pulvinar pathway was engaged during processing of these unseen target stimuli. Increased connectivity between right amygdala, pulvinar, and superior colliculus was evident when fear conditioned faces were unseen rather than seen. Right amygdala connectivity with fusiform and orbitofrontal cortices decreased in the same condition. By contrast, the left amygdala, whose activity did not discriminate seen and unseen fear conditioned targets, showed no masking-dependent changes in connectivity with superior colliculus or pulvinar. These results suggest that a subcortical pathway to the right amygdala, via midbrain and thalamus, provides a route for processing behaviorally relevant unseen visual events in parallel to a cortical route necessary for conscious identification. PMID- 9990085 TI - The 70-kDa heat shock cognate protein (Hsc73) gene is enhanced by ovarian hormones in the ventromedial hypothalamus. AB - Estrogen (E) and progesterone (P) orchestrate many cellular responses involved in female reproductive physiology, including reproductive behaviors. E- and P binding neurons important for lordosis behavior have been located within the ventromedial hypothalamus (VMH), and several hormone-responsive genes have been observed there as well. In attempts to identify additional E- and P-responsive genes in the VMH that may contribute to sexual behaviors, we used the differential display mRNA screening technique. One of the genes identified encodes the 73-kDa heat shock cognate protein (Hsc73). Quantitative in situ hybridization analysis of brains from naturally cycling female rats revealed a significant increase in Hsc73 mRNA in the VMH and arcuate nucleus of animals during proestrus compared with those at diestrus-1. To confirm that these increases were steroid hormone dependent, we compared vehicle-treated ovariectomized females with ovariectomized females treated with estradiol benzoate and P. Northern analysis and in situ hybridizations showed that the Hsc73 gene is enhanced by E and P in the pituitary and subregions of the VMH. Incidentally, by examining the primary amino acid sequence of rat, human, and chicken progesterone receptors, we noticed that putative Hsc73 binding sites are conserved across species with similar sites existing in the androgen and glucocorticoid receptors. Together these findings suggest a possible mechanism through which E could influence the activities of progesterone, androgen, and glucocorticoid receptors, by enhancing the expression of Hsc73 in cells where these proteins colocalize. PMID- 9990086 TI - Pronounced pharmacologic deficits in M2 muscarinic acetylcholine receptor knockout mice. AB - Members of the muscarinic acetylcholine receptor family (M1-M5) are known to be involved in a great number of important central and peripheral physiological and pathophysiological processes. Because of the overlapping expression patterns of the M1-M5 muscarinic receptor subtypes and the lack of ligands endowed with sufficient subtype selectivity, the precise physiological functions of the individual receptor subtypes remain to be elucidated. To explore the physiological roles of the M2 muscarinic receptor, we have generated mice lacking functional M2 receptors by using targeted mutagenesis in mouse embryonic stem cells. The resulting mutant mice were analyzed in several behavioral and pharmacologic tests. These studies showed that the M2 muscarinic receptor subtype, besides its well documented involvement in the regulation of heart rate, plays a key role in mediating muscarinic receptor-dependent movement and temperature control as well as antinociceptive responses, three of the most prominent central muscarinic effects. These results offer a rational basis for the development of novel muscarinic drugs. PMID- 9990087 TI - Increased anxiety and altered responses to anxiolytics in mice deficient in the 65-kDa isoform of glutamic acid decarboxylase. AB - The larger isoform of the enzyme glutamate decarboxylase, GAD67, synthesizes >90% of basal levels of gamma-aminobutyric acid (GABA) in the brain. In contrast, the smaller isoform, GAD65, has been implicated in the fine-tuning of inhibitory neurotransmission. Mice deficient in GAD65 exhibit increased anxiety-like responses in both the open field and elevated zero maze assays. Additionally, GAD65-deficient mice have a diminished response to the anxiolytics diazepam and pentobarbital, both of which interact with GABA-A receptors in a GABA-dependent fashion to facilitate GABAergic neurotransmission. Loss of GAD65-generated GABA does not appear to result in compensatory postsynaptic GABA-A receptor changes based on radioligand receptor binding studies, which revealed no change in the postsynaptic GABA-A receptor density. Furthermore, mutant and wild-type animals do not differ in their behavioral response to muscimol, which acts independently of the presence of GABA. We propose that stress-induced GABA release is impaired in GAD65-deficient mice, resulting in increased anxiety-like responses and a diminished response to the acute effects of drugs that facilitate the actions of released GABA. PMID- 9990088 TI - Control of spine formation by electrical activity in the adult rat cerebellum. AB - Dendritic spines are a key structure in neuronal plasticity. Enhanced activity is commonly associated with an increase in spine size and density. Purkinje cell dendrites are characterized by a proximal and a distal compartment on which climbing fibers and parallel fibers, respectively, impinge. The proximal region has a very low spine density, whereas the distal region has a high density. Previous experiments showed that after climbing fiber deletion, Purkinje cells become hyperactive, and a large number of spines develop on the proximal dendrites. Here we show that the same hyperspiny transformation occurs in the proximal dendrites of adult Purkinje cells by depressing electrical activity with tetrodotoxin. Thus, spines in different dendritic compartments are created or maintained independently from the level of Purkinje cell-firing rate and when the afferent activity is blocked. This conclusion supports the view that spinogenesis is the expression of an intrinsic program and the two regions of the dendritic tree respond differently to activity block because of differences in the inputs that they receive. On tetrodotoxin treatment, climbing fibers become atrophic and may sprout thin collateral ramifications directed mainly toward the granular layer. All changes are reversible on tetrodotoxin removal. Therefore, Purkinje cells provide a model where spines in different compartments of the same neuron are differently regulated by the activity of their local afferents. In addition, electrical activity is also essential to maintain the full climbing fiber innervation. PMID- 9990089 TI - Two serine residues of the glutamate transporter GLT-1 are crucial for coupling the fluxes of sodium and the neurotransmitter. AB - The neurotoxicity of glutamate in the central nervous system is restricted by several (Na+ + K+)-coupled transporters for this neurotransmitter. The astroglial transporter GLT-1 is the only subtype that exhibits high sensitivity to the nontransportable glutamate analogue dihydrokainate. A marked reduction in sensitivity to the blocker is observed when serine residues 440 and 443 are mutated to glycine and glutamine, which, respectively, occupy these positions in the other homologous glutamate transporters. They are located in the ascending limb of the recently identified pore-loop-like structure. Strikingly, mutation of serine-440 to glycine enables not only sodium but also lithium ions to drive net influx of acidic amino acids. Moreover, the efficiency of lithium as a driving ion for glutamate transport depends on the nature of the amino acid residue present at position 443. Mutant transporters containing single cysteines at the position of either serine residue become sensitive to positively as well as negatively charged methanethiosulfonate derivatives. In S440C transporters significant protection against this inhibition is provided both by transportable and nontransportable glutamate analogues, but not by sodium alone. Our observations indicate that the pore-loop-like structure plays a pivotal role in coupling ion and glutamate fluxes and suggest that it is close to the glutamate binding site. PMID- 9990090 TI - Elimination of zinc from synaptic vesicles in the intact mouse brain by disruption of the ZnT3 gene. AB - The mammalian protein ZnT3 resides on synaptic vesicle membranes of zinc containing neurons, suggesting its possible role in vesicular zinc transport. We show here that histochemically reactive zinc, corresponding to the zinc found within synaptic vesicles, was undetectable in the brains of mice with targeted disruption of the ZnT3 gene. Total zinc levels in the hippocampus and cortex of these mice were reduced by about 20%. The ultrastructure of mossy fiber boutons, which normally store the highest levels of vesicular zinc, was unaffected. Mice with one normal ZnT3 allele had reduced levels of ZnT3 protein on synaptic vesicle membranes and had intermediate amounts of vesicular zinc. These results demonstrate that ZnT3 is required for transport of zinc into synaptic vesicles and suggest that vesicular zinc concentration is determined by the abundance of ZnT3. PMID- 9990092 TI - Disruption of the beta subunit of the epithelial Na+ channel in mice: hyperkalemia and neonatal death associated with a pseudohypoaldosteronism phenotype. AB - The epithelial Na+ channel (ENaC) is composed of three homologous subunits: alpha, beta and gamma. We used gene targeting to disrupt the beta subunit gene of ENaC in mice. The betaENaC-deficient mice showed normal prenatal development but died within 2 days after birth, most likely of hyperkalemia. In the -/- mice, we found an increased urine Na+ concentration despite hyponatremia and a decreased urine K+ concentration despite hyperkalemia. Moreover, serum aldosterone levels were increased. In contrast to alphaENaC-deficient mice, which die because of defective lung liquid clearance, neonatal betaENaC deficient mice did not die of respiratory failure and showed only a small increase in wet lung weight that had little, if any, adverse physiologic consequence. The results indicate that, in vivo, the beta subunit is required for ENaC function in the renal collecting duct, but, in contrast to the alpha subunit, the beta subunit is not required for the transition from a liquid-filled to an air-filled lung. The phenotype of the betaENaC-deficient mice is similar to that of humans with pseudohypoaldosteronism type 1 and may provide a useful model to study the pathogenesis and treatment of this disorder. PMID- 9990091 TI - beta-Endorphin blocks luteinizing hormone-releasing hormone release by inhibiting the nitricoxidergic pathway controlling its release. AB - beta-Endorphin blocks release of luteinizing hormone (LH)-releasing hormone (LHRH) into the hypophyseal portal vessels by stimulating mu-opiate receptors, thereby inhibiting secretion of LH. LHRH release is controlled by release of nitric oxide from nitricoxidergic (NOergic) neurons in the basal tuberal hypothalamus. To determine whether beta-endorphin exerts its inhibitory action on this NOergic pathway, medial basal hypothalami (MBH) from male rats were incubated with beta-endorphin (10(-8) M). beta-Endorphin decreased basal secretion of LHRH, and significantly inhibited the release of prostaglandin E2 (PGE2), a known stimulant of LHRH release. Incubation of MBH with beta-endorphin at various concentrations (10(-9)-10(-6) M) in vitro decreased the activity of NO synthase (NOS) (measured by the conversion of [14C]arginine to labeled citrulline). Conversely, the activity of NOS was increased by the mu-receptor antagonist, naltrexone (10(-8) M). Not only was the inhibitory action of beta endorphin on LHRH and PGE2 release blocked by naltrexone (10(-8) M), but it increased NOS activity and LHRH and PGE2 release. beta-Endorphin also stimulated gamma-aminobutyric acid (GABA) release. Because GABA inhibits both nitroprusside (NP-induced PGE2 and LHRH release by blocking the activation of cyclooxygenase by NO, this is another mechanism by which beta-endorphin inhibits NP-induced PGE2 and LHRH release. The results indicate that beta-endorphin stimulates mu-opioid receptors on NOergic neurons to inhibit the activation and consequent synthesis of NOS in the MBH. beta-Endorphin also blocks the action of NO on PGE2 release and, consequently, on LHRH release, by stimulating GABAergic inhibitory input to LHRH terminals that blocks NO-induced activation of cyclooxygenase and consequent PGE2 secretion. PMID- 9990093 TI - Salt restriction induces pseudohypoaldosteronism type 1 in mice expressing low levels of the beta-subunit of the amiloride-sensitive epithelial sodium channel. AB - The amiloride-sensitive epithelial sodium channel (ENaC) is a heteromultimer of three homologous subunits (alpha-, beta-, and gamma-subunits). To study the role of the beta-subunit in vivo, we analyzed mice in which the betaENaC gene locus was disrupted. These mice showed low levels of betaENaC mRNA expression in kidney (approximately 1%), lung (approximately 1%), and colon (approximately 4%). In homozygous mutant betaENaC mice, no betaENaC protein could be detected with immunofluorescent staining. At birth, there was a small delay in lung-liquid clearance that paralleled diminished amiloride-sensitive Na+ absorption in tracheal explants. With normal salt intake, these mice showed a normal growth rate. However, in vivo, adult betaENaC m/m mice exhibited a significantly reduced ENaC activity in colon and elevated plasma aldosterone levels, suggesting hypovolemia and pseudohypoaldosteronism type 1. This phenotype was clinically silent, as betaENaC m/m mice showed no weight loss, normal plasma Na+ and K+ concentrations, normal blood pressure, and a compensated metabolic acidosis. On low-salt diets, betaENaC-mutant mice developed clinical symptoms of an acute pseudohypoaldosteronism type 1 (weight loss, hyperkalemia, and decreased blood pressure), indicating that betaENaC is required for Na+ conservation during salt deprivation. PMID- 9990094 TI - A protein phosphatase 2C gene, LjNPP2C1, from Lotus japonicus induced during root nodule development. AB - Symbiotic interactions between legumes and compatible strains of rhizobia result in root nodule formation. This new plant organ provides the unique physiological environment required for symbiotic nitrogen fixation by the bacterial endosymbiont and assimilation of this nitrogen by the plant partner. We have isolated two related genes (LjNPP2C1 and LjPP2C2) from the model legume Lotus japonicus that encode protein phosphatase type 2C (PP2C). Expression of the LjNPP2C1 gene was found to be enhanced specifically in L. japonicus nodules, whereas the LjPP2C2 gene was expressed at a similar level in nodules and roots. A glutathione S-transferase-LjNPP2C1 fusion protein was shown to have Mg2+- or Mn2+ dependent and okadaic acid-insensitive PP2C activity in vitro. A chimeric construct containing the full-length LjNPP2C1 cDNA, under the control of the Saccharomyces cerevisiae alcohol dehydrogenase promoter, was found to be able to complement a yeast PP2C-deficient mutant (pct1Delta). The transcript level of the LjNPP2C1 gene was found to increase significantly in mature nodules, and its highest expression level occurred after leghemoglobin (lb) gene induction, a molecular marker for late developmental events in nodule organogenesis. Expression of the LjNPP2C1 gene was found to be drastically altered in specific L. japonicus lines carrying monogenic-recessive mutations in symbiosis-related loci, suggesting that the product of the LjNPP2C1 gene may function at both early and late stages of nodule development. PMID- 9990095 TI - Molecular basis for semidominance of missense mutations in the XANTHA-H (42-kDa) subunit of magnesium chelatase. AB - During biosynthesis of bacteriochlorophyll or chlorophyll, three protein subunits of 140, 70, and 42 kDa interact to insert Mg2+ into protoporphyrin IX. The semidominant Chlorina-125, -157, and -161 mutants in barley are deficient in this step and accumulate protoporphyrin IX after feeding on 5-aminolevulinate. Chlorina-125, -157, and -161 are allelic to the recessive xantha-h mutants and contain G559A, G806A, and C271T mutations, respectively. These mutations cause single amino acid substitutions in residues that are conserved in all known primary structures of the 42-kDa subunit. In vitro complementation and reconstitution of Mg-chelatase activity show that the 42-kDa subunits are defective in the semidominant Chlorina mutants. A mutated protein is maintained in the Chlorina plastids, unlike in the xantha-h plastids. Heterozygous Chlorina seedlings have 25-50% of the Mg-chelatase activity of wild-type seedlings. Codominant expression of active and inactive 42-kDa subunits in heterozygous Chlorina seedlings is likely to produce two types of heterodimers between the strongly interacting 42-kDa and 70-kDa subunits. Reduced Mg-chelatase activity is explained by the capacity of heterodimers consisting of mutated 42-kDa and wild type 70-kDa protein to bind to the 140-kDa subunit. The 42-kDa subunit is similar to chaperones that refold denatured polypeptides with respect to its ATP-to-ADP exchange activity and its ability to generate ATPase activity with the 70-kDa subunit. We hypothesize that the association of the 42-kDa subunit with the 70 kDa subunit allows them to form a specific complex with the 140-kDa subunit and that this complex inserts Mg2+ into protoporphyrin IX. PMID- 9990096 TI - Expression of a soybean cytochrome P450 monooxygenase cDNA in yeast and tobacco enhances the metabolism of phenylurea herbicides. AB - A strategy based on the random isolation and screening of soybean cDNAs encoding cytochrome P450 monooxygenases (P450s) was used in an attempt to identify P450 isozymes involved in herbicide metabolism. Nine full-length (or near-full-length) P450 cDNAs representing eight distinct P450 families were isolated by using PCR based technologies. Five of the soybean P450 cDNAs were expressed successfully in yeast, and microsomal fractions generated from these strains were tested for their potential to catalyze the metabolism of 10 herbicides and 1 insecticide. In vitro enzyme assays showed that the gene product of one heterologously expressed P450 cDNA (CYP71A10) specifically catalyzed the metabolism of phenylurea herbicides, converting four herbicides of this class (fluometuron, linuron, chlortoluron, and diuron) into more polar compounds. Analyses of the metabolites suggest that the CYP71A10 encoded enzyme functions primarily as an N-demethylase with regard to fluometuron, linuron, and diuron, and as a ring-methyl hydroxylase when chlortoluron is the substrate. In vivo assays using excised leaves demonstrated that all four herbicides were more readily metabolized in CYP71A10 transformed tobacco compared with control plants. For linuron and chlortoluron, CYP71A10-mediated herbicide metabolism resulted in significantly enhanced tolerance to these compounds in the transgenic plants. PMID- 9990097 TI - A wound- and systemin-inducible polygalacturonase in tomato leaves. AB - Oligogalacturonide fragments that activate defensive genes in plant leaves heretofore have been thought to be generated only by pathogen-derived pectin degrading enzymes, because polygalacturonase (PG) activity has not been reported in leaves. Here, we report that mRNAs encoding a PG catalytic subunit protein and its regulatory (beta-subunit) protein are expressed in tomato leaves in response to wounding, systemin, and oligosaccharide elicitors. Synthesis of the two subunits in response to wounding is systemic and is accompanied by an increase in PG activity in extracts from both wounded and unwounded leaves. The finding that PG subunit mRNAs and PG enzyme activity are induced by wounding indicates that herbivore attacks can produce endogenous oligogalacturonide elicitors that may be involved in the local and systemic activation of defense responses against both herbivores and pathogens. PMID- 9990098 TI - The tomato DWARF enzyme catalyses C-6 oxidation in brassinosteroid biosynthesis. AB - Brassinosteroids (BRs) are steroidal plant hormones essential for normal plant growth and development. Mutants in the biosynthesis or perception of BRs are usually dwarf. The tomato Dwarf gene (D), which was predicted to encode a cytochrome P450 enzyme (P450) with homology to other P450s involved in BR biosynthesis, was cloned previously. Here, we show that DWARF catalyses the C-6 oxidation of 6-deoxocastasterone (6-deoxoCS) to castasterone (CS), the immediate precursor of brassinolide. To do this, we first confirmed that the D cDNA complemented the mutant light- and dark-grown phenotypes of the extreme dwarf (dx) allele of tomato. To identify a substrate for the DWARF enzyme, exogenous application of BR intermediates to dx plants was carried out. C-6 oxoBR intermediates enhanced hypocotyl elongation whereas the C-6 deoxoBR, 6-deoxoCS, had little effect. Quantitative analysis of endogenous BR levels in tomato showed mainly the presence of 6-deoxoBRs. Furthermore, dx plants were found to lack CS and had a high level of 6-deoxoCS in comparison to D plants that had CS and a lower level of 6-deoxoCS. Confirmation that DWARF catalyzed the C-6 oxidation of 6-deoxoCS to CS was obtained by functional expression of DWARF in yeast. In these experiments, the intermediate 6alpha-hydroxycastasterone was identified, indicating that DWARF catalyzes two steps in BR biosynthesis. These data show that DWARF is involved in the C-6 oxidation in BR biosynthesis. PMID- 9990100 TI - Chromosome regions between centromeres and proximal crossovers are the physical sites of major effect loci for yield in potato: genetic analysis employing meiotic mutants. AB - Meiotic mutant (2n) gametes formed by first-division restitution without crossover (FDR-NCO) are expected to be superior to FDR with crossover (FDR-CO) because they transmit to the progeny, without disruption by recombination, almost 100% of the parental genotype. FDR-CO transfers approximately 80% of the parental heterozygosity and a large fraction of the epistatic interactions. Another genetic expectation associated with both FDR gametes is their equivalence for the phenotypic expression of traits controlled by genes residing between centromeres and proximal crossover sites. This set of unique cytogenetic features of FDR mutants was employed here as a tool to infer physical location of quantitative trait loci controlling total tuber yield (TTY) in potato. Two assays were conducted to verify the superiority of FDR-NCO over FDR-CO gametes for TTY by using progenies from 4x-2x factorial crosses. Male clones were 2n-pollen producers by either FDR-CO or FDR-NCO mechanisms. Compared with the 4x parents, TTY of the progenies ranged from 41% to 175% (i.e., high-parent heterosis). However, no significant TTY differences were observed between FDR-CO and FDR-NCO families. In addition, the size of variance components of males was smaller than females and near zero. Our results reinforce the hypothesis that genes controlling yielding ability have a predominant physical location between centromeres and proximal chiasmata. Quantitative trait loci in chromosome regions with reduced levels of recombination may provide a partial explanation for the slow progress in increasing TTY through conventional 4x-4x crosses and for the often high degree of heterosis obtained by introgressing genetic diversity via 4x 2x crosses in potato. PMID- 9990099 TI - An abscisic acid-induced protein kinase, PKABA1, mediates abscisic acid suppressed gene expression in barley aleurone layers. AB - The phytohormone abscisic acid (ABA) induces genes-encoding proteins involved in desiccation tolerance and dormancy in seeds, but ABA also suppresses gibberellin (GA)-responsive genes encoding hydrolytic enzymes essential for postgermination growth. A unique serine/threonine protein kinase, PKABA1 mRNA, up-regulated by ABA in seeds, has been identified. In this report, the effect of PKABA1 on the signal transduction pathway mediating ABA induction and suppression of genes has been determined in aleurone layers of barley seeds. Two groups of gene constructs were introduced to barley aleurone layers by using particle bombardment: the reporter constructs containing the coding sequence of beta-glucuronidase gene linked to hormone-responsive promoters and the effector constructs containing the coding region of protein kinases linked to a constitutive promoter. Constitutive expression of PKABA1 drastically suppressed expression of low- and high-pI alpha amylase and protease genes induced by GA. However, the presence of PKABA1 had only a small effect on the ABA induction of a gene encoding a late embryogenesis abundant protein, HVA1. Our results indicate that PKABA1 acts as a key intermediate in the signal transduction pathway leading to the suppression of GA inducible gene expression in cereal aleurone layers. PMID- 9990101 TI - Abscisic acid induces oscillations in guard-cell cytosolic free calcium that involve phosphoinositide-specific phospholipase C. AB - Oscillations in cytosolic free Ca2+ concentration ([Ca2+]cyt) are an important component of Ca2+-based signal transduction pathways. This fact has led us to investigate whether oscillations in [Ca2+]cyt are involved in the response of stomatal guard cells to the plant hormone abscisic acid (ABA). We show that ABA induces oscillations in guard-cell [Ca2+]cyt. The pattern of the oscillations depended on the ABA concentration and correlated with the final stomatal aperture. We examined the mechanism by which ABA generates oscillations in guard cell [Ca2+]cyt by using 1-(6-[17beta-3-methoxyestra-1,3, 5(10)-trien-17 yl]aminohexyl)-1H-pyrrole-2,5-dione (U-73122), an inhibitor of phosphoinositide specific phospholipase C (PI-PLC)-dependent processes in animals. U-73122 inhibited the hydrolysis of phosphatidylinositol 4,5-bisphosphate by a recombinant PI-PLC, isolated from a guard-cell-enriched cDNA library, in a dose dependent manner. This result confirms that U-73122 is an inhibitor of plant PI PLC activity. U-73122 inhibited both ABA-induced oscillations in [Ca2+]cyt and stomatal closure. In contrast, U-73122 did not inhibit external Ca2+-induced oscillations in guard-cell [Ca2+]cyt and stomatal closure. Furthermore, there was no effect of the inactive analogue 1-(6-[17beta-3-methoxyestra-1,3, 5(10)-trien 17-yl]aminohexyl)-2,5-pyrrolidinedione on recombinant PI-PLC activity or ABA induced and external Ca2+-induced oscillations in [Ca2+]cyt and stomatal closure. This lack of effect suggests that the effects of U-73122 in guard cells are the result of inhibition of PI-PLC and not a consequence of nonspecific effects. Taken together, our data suggest a role for PI-PLC in the generation of ABA induced oscillations in [Ca2+]cyt and point toward the involvement of oscillations in [Ca2+]cyt in the maintenance of stomatal aperture by ABA. PMID- 9990102 TI - Habitat, world geographic range, and embryonic development of hosts explain the prevalence of avian hematozoa at small spatial and phylogenetic scales. AB - The factors explaining interspecific differences in prevalences of blood parasites in birds are poorly known. We simultaneously assessed 20 social, ecological, life history, and sampling-related variables that could influence hemoparasite prevalences among diurnal birds of prey in Spain. Our results show that multiple factors are responsible for the studied host-parasite association. We confirmed for the first time that prevalence is inversely correlated to the embryonic development period, and thus probably to immune performance, even among closely related birds. Macrohabitat features related to vector availability are also important, prevalences being higher in species breeding in forested habitats. Finally, prevalence is positively correlated with the host's world geographic range. We hypothesize that larger geographic ranges offered more opportunities for host-vector-hemoparasite associations to become established. The results from our multivariate analyses differ from those obtained through univariate ones, showing that all potential factors should be assessed jointly when testing any ecological or evolutionary hypothesis dealing with parasites. PMID- 9990103 TI - Localizing the cortical region mediating visual awareness of object identity. AB - Presentations of pictures that are too brief to be recognized, or even guessed above chance on a forced-choice test, nonetheless can facilitate the recognition of the same pictures many trials later. This subliminal visual priming was compared for images translated 4. 8 degrees either Within or Between quadrants of the visual field. Priming was evident only for images that remained within the same quadrant in priming and test trials. Consequently, subliminal visual priming is likely mediated by cortical areas in which cells have receptive fields large enough to respond to both presentations of a stimulus translated almost 5 degrees, yet where the receptive fields are confined to a single quadrant, namely, the human homologue of macaque V4 or TEO (the posterior part of the inferior temporal cortex). Awareness of object identity might therefore be associated exclusively with activity at or beyond the anterior part of the inferior temporal cortex, namely, area TE. PMID- 9990104 TI - Task-related and item-related brain processes of memory retrieval. AB - In all cognitive tasks, general task-related processes operate throughout a given task on all items, whereas specific item-related processes operate differentially on individual items. In typical functional neuroimaging experiments, these two sets of processes have usually been confounded. Herein we report a combined positron emission tomography and event-related potential (ERP) experiment that was designed to distinguish between neural correlates of task-related and item related processes of memory retrieval. Two retrieval tasks, episodic and semantic, were crossed with episodic (old/new) and semantic (living/nonliving) properties of individual items to yield evidence of regional brain activity associated with task-related processes, item-related processes, and their interaction. The results showed that episodic retrieval task was associated with increased blood flow in right prefrontal and posterior cingulate cortex, as well as with a sustained right-frontopolar-positive ERP, but that the semantic retrieval task was associated with left frontal and temporal lobe activity. Retrieval of old items was associated with increased blood flow in the left medial temporal lobe and with a brief late positive ERP component. The results provide converging hemodynamic and electrophysiological evidence for the distinction of task- and item-related processes, show that they map onto spatially and temporally distinct patterns of brain activity, and clarify the hemispheric encoding/retrieval asymmetry (HERA) model of prefrontal encoding and retrieval asymmetry. PMID- 9990105 TI - Hypoglossal canal size and hominid speech. AB - The mammalian hypoglossal canal transmits the nerve that supplies the motor innervation to the tongue. Hypoglossal canal size has previously been used to date the origin of human-like speech capabilities to at least 400,000 years ago and to assign modern human vocal abilities to Neandertals. These conclusions are based on the hypothesis that the size of the hypoglossal canal is indicative of speech capabilities. This hypothesis is falsified here by the finding of numerous nonhuman primate taxa that have hypoglossal canals in the modern human size range, both absolutely and relative to oral cavity volume. Specimens of Australopithecus afarensis, Australopithecus africanus, and Australopithecus boisei also have hypoglossal canals that, both absolutely and relative to oral cavity volume, are equal in size to those of modern humans. The basis for the hypothesis that hypoglossal canal size is indicative of speech was the assumption that hypoglossal canal size is correlated with hypoglossal nerve size, which in turn is related to tongue function. This assumption is probably incorrect, as we found no apparent correlation between the size of the hypoglossal nerve, or the number of axons it contains, and the size of the hypoglossal canal in a sample of cadavers. Our data demonstrate that the size of the hypoglossal canal does not reflect vocal capabilities or language usage. Thus the date of origin for human language and the speech capabilities of Neandertals remain open questions. PMID- 9990106 TI - Neandertal nasal structures and upper respiratory tract "specialization". AB - Schwartz and Tattersall [Schwartz, J. H. & Tattersall, I. (1996) Proc. Natl. Acad. Sci. USA 93, 10852-10854] have argued for a previously unrecognized suite of autapomorphies in the internal nasal region of Neandertals that make them unique, not only among hominids, but possibly among all other terrestrial mammals. These purported autapomorphies include (i) the development of an internal nasal margin bearing a well developed and vertically oriented medial projection; (ii) a pronounced medial swelling of the lateral nasal wall into the posterior nasal cavity; and (iii) the lack of an ossified roof over the lacrimal groove. In addition, Laitman et al. [Laitman, J. T., Reidenberg, J. S., Marquez, S. & Gannon, P. J. (1996) Proc. Natl. Acad. Sci. USA 93, 10543-10545] pointed to these features as evidence for upper respiratory tract specializations among the Neandertals, indicating potential differences in behavior compared with modern humans. Critically reviewing the anatomical basis for Schwartz and Tattersall's contentions reveals several serious problems with their analysis, including (i) reliance on specimens with damaged, incomplete, or, in some cases, entirely absent relevant anatomy; (ii) failure to consider primary vs. secondary spatial consequences in nasal trait conceptualization; and (iii) failure to consider actual ranges of variation in these traits in both fossil and recent humans. Accordingly, the unique phylogenetic and adaptive "specializations" attributed to Neandertal internal nasal structures are unwarranted. PMID- 9990107 TI - Infiltrative subcutaneous malignant fibrous histiocytoma: a comparative study with deep malignant fibrous histiocytoma and an observation of biologic behavior. AB - Malignant fibrous histiocytoma (MFH) is one of the most common soft tissue sarcomas of adulthood. Although it is usually intramuscular and pseudocapsulated, we have recently observed MFHs with extremely infiltrative growth margins, which are predominantly located in the subcutis. These lesions are often associated with incomplete primary surgical excision, the subsequent need for additional surgery or adjuvant therapy, and an increased risk for local recurrence. To further analyze the growth pattern and clinical implication of the subcutaneous infiltrative MFHs, we reviewed a series of 24 subcutis and 21 intramuscular MFHs of the extremities. Morphologically, we defined "infiltrative" as tumor extension along normal tissue planes for a minimum measurable distance of 2 mm from the edge of the main mass. Radiographic findings were correlated with pathologic findings. Of the 24 subcutis MFHs, 83% showed an infiltrative growth pattern, involving 5% to 90% (mean, 51%) of the evaluable margin. Fifty percent of patients with subcutaneous MFH had both an infiltrative growth pattern and positive surgical resection margin on initial resection. Only 25% noninfiltrative subcutaneous MFHs had a positive initial surgical resection margin. Of the 21 intramuscular MFHs, only 5 (24%) had an infiltrative growth pattern that involved 5% to 90% (mean, 40%) of the evaluable margin. One of the five tumors had 90% margin infiltration with multiple positive surgical resection margins. Of 16 noninfiltrative intramuscular MFHs, 3 (19%) had positive resection margins. Magnetic resonance imaging (MRI) and/or computed tomography (CT) scan correctly identified the growth pattern in 87% of subcutaneous and 88% of intramuscular MFHs. Patient follow-up evaluation showed that four (17%) patients with subcutaneous MFHs had resection-proven recurrences, 6 to 57 months after diagnosis. All four of these tumors had infiltrative growth patterns and positive margins on the original surgical resection. There were no local recurrences of the intramuscular MFHs. Two patients of 20 in the infiltrative subcutaneous MFH group and two patients of four in the well-circumscribed subcutaneous MFH group had biopsy-proven metastases, which developed within 5 years after diagnosis. Six patients had metastases in the intramuscular MFH group. A group of MFHs, predominantly subcutaneous, have an extremely infiltrative growth pattern. This growth pattern, documented by radiographic methods and/or light microscopic examination of biopsy specimens, should indicate that a wider margin on initial resection is necessary to entirely excise the lesion. The presence or absence of an infiltrative growth pattern is not predictive of the tumor's metastatic potential. PMID- 9990108 TI - Clinicopathologic study of 61 patients with ependymoma including MIB-1 immunohistochemistry. AB - Predicting behavior based on histologic appearance has been problematic in ependymomas. Sixty-one patients with ependymoma (excluding subependymoma and myxopapillary ependymoma) were studied. The patients included 36 men and ranged in age from 1.5 to 74 years (median, 33 years). The most common clinical presentations included headache (n = 19), weakness (n = 18), nausea/vomiting (n = 12), and gait disturbance (n = 10). Location included spinal cord (n = 24), fourth ventricle (n = 21), lateral ventricle (n = 8), and third ventricle (n = 5). Initial surgery included a gross total resection of tumor in 22 patients and subtotal resection or biopsy in the remaining patients. Thirty-five patients were known to have been treated with adjuvant radiation therapy and 13 patients received adjuvant chemotherapy. At last known follow-up, 20 patients were alive with no evidence of tumor (median, 66.5 months), 17 patients were alive with residual tumor (median, 14 months), and 12 patients died of tumor (median, 27.5 months). Two additional patients are alive with tumor status not known, two cases are current, and two patients were lost to follow-up. The additional six patients died either shortly after surgery or of surgical complications. Sixteen of 18 patients had at least one tumor recurrence at median 28.5 months. Fifty-one tumors had a predominantly glial pattern and 10 had a mixed glial-epithelial pattern. Of histologic features examined, patients with tumor recurrence or who died of tumor more frequently had observable mitotic figures, vascular proliferation, necrosis, and foci of increased cellularity. Eight of 18 recurrent tumors were classified as high grade ependymomas (anaplastic/malignant). Of patients who died of tumor, 4 of 12 had histologically high grade tumors versus 5 of 39 of the remaining tumors. MIB-1 immunostaining (marker of cell proliferation) was performed on 50 tumors. MIB-1 labeling indices (% positive tumor cell nuclei) ranged from 0.1 to 34.0 (median, 1.1). A higher percentage of patients with recurrent tumor (6 of 13, 46%) or who died of tumor (3 of 10, 30%) had MIB-1 indices >/= 4.0 versus the remaining patients (8 of 33, 24%). The conclusions are as follows: (1) histologic appearance and MIB-1 indices were not reliably predictive of tumor behavior, probably due in part to tumor heterogeneity; (2) tumors with two or more of the following features: identifiable mitotic figures, hypercellularity, vascular proliferation, and necrosis were more likely to behave in an aggressive manner; and (3) elevated MIB 1 labeling indices (>/=4.0 in this study) were encountered in a higher percentage of fatal and recurrent tumors than in nonfatal or nonrecurrent tumors. PMID- 9990109 TI - Are there cytopathic features associated with cytomegalovirus infection predictive of resistance to antiviral therapy? AB - Recent awareness of the broader spectrum of morphologic changes induced by cytomegalovirus (CMV) infection prompted us to investigate whether the concurrent introduction of effective antiviral therapy is in some way related to the appearance of atypical cytopathic features. These changes may be easily misinterpreted on histologic examination as reactive or degenerative. In addition, since resistant strain to antiviral therapy has emerged and its demonstration is a laborious process performed in highly specialized laboratories, it is important to determine if resistance to antiviral drugs can be predicted from the microscopic examination of infected tissues. The population consisted of seven immunosuppressed patients with documented CMV infection from which 18 tissue samples were obtained at autopsy or endoscopically. Antiviral susceptibility to ganciclovir was determined by plaque reduction assay and/or a DNA-DNA hybridization method. Eleven tissue specimens from patients harboring resistant strains were compared with seven specimens from patients infected with sensitive strains. Cytopathic changes were classified as typical or atypical according to previously published criteria. Of the 18 biopsy specimens, the cytopathic changes were distributed as follows: typical 1, typical and atypical 5, and atypical 12. Atypical inclusions were found in 10 of 11 and 7 of 7 sensitive and resistant cases, respectively. In conclusion, there are no specific morphologic features in CMV-infected tissues of patients with infections caused by ganciclovir resistant strains. PMID- 9990110 TI - Composite B-cell and T-cell lymphoma arising 24 years after nodular lymphocyte predominant Hodgkin's disease. AB - Twenty-four years after apparently successful treatment for nodular lymphocyte predominant Hodgkin's disease (nLPHD), a 41-year old male developed "B" symptoms and extensive adenopathy. A right axillary lymph node biopsy showed two distinct regions including (1) histiocyte-rich B-cell lymphoma and (2) diffuse small T cell lymphoma. A clonal rearrangement of the gene for the T-cell receptor beta chain confirmed the presence of a T-cell neoplasm, and this was further confirmed by selective polymerase chain reaction (PCR) on this morphologic zone. PCR on the morphologic B-cell lymphoma confirmed the presence of an immunoglobulin gene rearrangement. These two regions were separated by a less-defined zone containing a mixture of small CD57 positive T lymphocytes, small B lymphocytes, and rare lymphocytic and histiocytic (L&H) cells, highly suggestive of recurrent LPHD. The development of composite B-cell and T-cell lymphoma in this patient raises the speculation that nLPHD may be a neoplasm of lymphoid cells, which can differentiate in both B- and T-cell directions, with the "L&H" cells constituting their B-cell progeny. PMID- 9990111 TI - Granular cell tumor of the parotid. AB - A case of granular cell tumor of the major salivary glands is presented. This tumor appeared as an expansive multinodular mass that arose from facial nerve trunks. The presenting symptoms of facial pain and paresis and the intraoperative findings of tumor adhesion to nerves led to the clinical impression of malignancy. At intraoperative consultation, the tumor resembled an acinic cell carcinoma. Pathologists should be aware that granular cell tumors may involve the major salivary glands and that it should be considered in the diagnostic differential diagnosis. PMID- 9990112 TI - Intraductal carcinoma (carcinoma in situ) of the pancreas with microinvasion. AB - We report a case of predominantly intraductal carcinoma of the pancreas with microscopic foci of invasive carcinoma in a patient with chronic pancreatitis. In this article, we discuss the pathologic and prognostic features of pancreatic carcinoma in situ. This entity is probably overlooked due to a number of reasons, including the fact that, in most cases, pancreatic ductal carcinomas are extensively infiltrative at the time of surgical removal; the atypical epithelial changes in the intraductal carcinoma had been overlooked in the presence or absence of an invasive component; epithelial changes may be missed due to insufficient sampling; and last, the differentiation with atypical epithelial hyperplasia is a subjective matter. Intraductal carcinoma of the pancreas is a distinct pathological entity with characteristic morphologic changes restricted to the ductal epithelium, bearing important prognostic implications. PMID- 9990113 TI - Histologic prognostication in soft tissue sarcomas: grading versus subtyping or both? A comprehensive review of the literature with proposed practical guidelines. AB - Despite the validation of many histologic grading systems for soft tissue sarcomas, none have been universally accepted. Because of the overall rarity of specific histologic sarcoma subtypes, evaluation of grading systems and their prognostic significance have tended to base the results on sarcomas as a general group, diminishing the value and significance of histologic subtyping. A representative review of the literature regarding histologic grading of soft tissue sarcomas and its relationship to histologic subtype, stage, and prognosis is analyzed and discussed. Histologic grading of many soft tissue sarcomas appears to be a valuable predictor of patient survival, as confirmed by the literature. However, accurate histologic subtyping is essential for accurate histologic grading. Histologic grading in some sarcoma subtypes is probably not applicable and may underestimate biologic behavior. Clinicians and pathologists should be aware of the limitations, prognostic significances, and relationships of histologic subtyping and histologic grading in the therapeutic management and prognostication of soft tissue sarcomas. PMID- 9990114 TI - Three famous autopsies. AB - George II, the King of England, died from dissecting aneurism of the aorta. Napoleon died from a carcinoma of the stomach. Frederick III, Emperor of Germany, died of a laryngeal cancer; his untimely death, and the succession of his son, Wilhelm II, was largely responsible for the great catastrophe of 1914. An autopsy was performed on each of these three famous and historical figures. PMID- 9990116 TI - CpG islands in chromatin organization and gene expression. AB - CpG islands are stretches of DNA sequence that are enriched in the (CpG)n repeat and are present in close association with all housekeeping genes as well as some tissue-specific genes in the mammalian genome. Methylation of CpG islands strongly influences both structural organization and function of chromatin. The presence of a CpG island in a given chromosomal domain can, by itself, give rise to relatively open and active chromatin. Recently, several histone acetyltransferases, histone deacetylases, and chromatin remodeling factors have been found to be part of the transcription machinery. It is becoming increasingly clear that CpG islands and their methylation status may influence the function or recruitment of these newly discovered chromatin remodeling factors, especially the histone deacetylases. In addition, CpG islands may also play a significant role in the reorganization of chromatin during mammalian spermiogenesis. PMID- 9990117 TI - Ubiquitin system: selectivity and timing of protein destruction. AB - A growing number of cellular functions have been shown to be regulated through protein degradation. The selective degradation of many short-lived proteins in eukaryotic cells is mediated by the ubiquitin system, by which proteins covalently ligated to ubiquitin are targeted for degradation. The selectivity of the destruction is ensured by the substrate specificity in the ubiquitination steps composed of a series of enzymatic reactions. Ubiquitin-ligase (E3), in conjunction with ubiquitin-conjugating enzyme (E2), has been implicated as playing an essential role in the substrate recognition. The substantial character, however, of the ligase was not clear until several recent studies demonstrated ligases that exert key roles in irreversible steps of the cell-cycle control. In this review, attention is focused on the molecular basis of target recognition of ubiquitination, particularly as exemplified in the ubiquitin ligases in the cell-cycle control mechanisms. PMID- 9990118 TI - Identification and characterization of a Drosophila homologue of the yeast UBC9 and hus5 genes. AB - The yeast UBC9 and hus5 gene products have been identified as putative E2 members of the ubiquitin-conjugating enzyme (UBC) family and have been shown to play an essential role in cell cycle progression. We have identified a Drosophila Ubc9/Hus5 homologue (termed dUBC9) in an attempt to identify proteins that interact with the amino-terminal transcriptional repression domain of the Groucho corepressor by use of the yeast two-hybrid system. The predicted dUBC9 protein consists of 159 amino acids and shows 85, 68, and 54% amino acid sequence identities with human UBC9 homologue, Schizosaccharomyces pombe Hus5, and Saccharomyces cerevisiae Ubc9 proteins, respectively. Expression of dUBC9 cDNA complements a temperature-sensitive ubc9-1 mutation of S. cerevisiae to fully restore normal growth, indicating that the dUBC9 protein can act as a substitute for the yeast Ubc9 protein. The dUBC9 transcripts were about 1.2 kb and were detected at all stages of Drosophila development and in ovaries and Schneider cells. However, an increased level was observed in early embryos and ovaries. The dUBC9 gene is present as a single copy in the genome and localized in segment 21C D on the left arm of the second chromosome. PMID- 9990119 TI - DNA helicase III of Saccharomyces cerevisiae, encoded by YER176w (HEL1), highly unwinds covalently closed, circular DNA in the presence of a DNA topoisomerase and yRF-A. AB - Previously, we have purified and characterized DNA helicase III from the yeast Saccharomyces cerevisiae [Shimizu, K. and Sugino, A. (1993) J. Biol. Chem. 268, 9578-9584]. Here, we have further characterized DNA helicase III activity. It was found that the combined action of the helicase III, yeast DNA topoisomerase I (yTop I), and yeast RPA protein on a covalently closed, circular DNA generates a highly underwound DNA species that has been called form I* or form U. Furthermore, these underwound structures can be accessed by yeast DNA polymerase I (alpha)-primase to initiate DNA synthesis. These reactions mimic in vivo initiation of chromosomal DNA replication. In order to clone the gene encoding DNA helicase III, a partial amino acid sequence of the purified DNA helicase III polypeptide was determined. Using a mix oligonucleotides synthesized based on the amino acid sequence of the helicase, we cloned the gene encoding the helicase III and found it to be identical to YER176W (HEL1) on chromosome V. The amino acid sequence predicted from the nucleotide sequence of the gene has conserved DNA helicase domains that are highly homologous to those of DNA helicases required for DNA replication. However, complete deletion of the gene from the chromosome did not result in any growth defect, suggesting that the gene product is not required for DNA synthesis or that it is functionally substituted by other helicase(s). Furthermore, the deletion strain does not exhibit sensitivity to any DNA-damaging reagents, although it is hypersensitive to calcofluor white, hygromycin, and papulacandin. PMID- 9990121 TI - Cellular and functional characterization of three recombinant antithrombin mutants that caused pleiotropic effect-type deficiency. AB - Inherited antithrombin deficiency is associated with a predisposition for familial venous thromboembolic disease. Pleiotropic effect-type mutants of antithrombin that have an amino acid replacement in a distal hinge region including strands 1C, 4B, and 5B of the polypeptide chain are known to exhibit impaired interactions with both thrombin and heparin, coupled with a secretion defect. To examine the mechanism of pleiotropic effect-type antithrombin deficiency, we expressed three mutants, Oslo (Ala404-->Thr), Kyoto (Arg406- >Met), and Utah (Pro407-->Leu), in baby hamster kidney (BHK) cells, and compared their secretion rates, affinities for heparin and abilities to form thrombin antithrombin (TAT) complexes with those of wild-type (Wt) antithrombin. Pulse chase experiments showed that the Oslo- and Kyoto-mutants were secreted at rates similar to Wt antithrombin. In contrast, the Utah-mutant underwent partial intracellular degradation. The intracellular degradation of the Utah-mutant was not inhibited by lysosomotropic inhibitors, but by proteasome inhibitors such as carbobenzoxy-L-leucyl-L-leucyl-L-leucinal (LLL) and lactacystin, indicating that a part of the Utah-mutant was degraded by proteasome through quality control in the endoplasmic reticulum (ER). Crossed immunoelectrophoresis in the presence of heparin showed that only the Oslo-mutant lacks heparin-binding ability. Incubation with thrombin showed that the Kyoto- and Utah-mutants, but not the Oslo-mutant, formed a weak but detectable TAT complex. Furthermore, heparin enhanced the TAT complex formation by the Kyoto- and Utah-mutants, suggesting heparin cofactor activities of these mutants. These results show that each of the Oslo-, Kyoto-, and Utah-mutants exhibits different properties as to secretion, intracellular degradation and functional activity, although they are grouped as pleiotropic effect-type mutants. PMID- 9990120 TI - Measurement of activities of human serum sulfotransferases which transfer sulfate to the galactose residues of keratan sulfate and to the nonreducing end N acetylglucosamine residues of N-acetyllactosamine trisaccharide: comparison between normal controls and patients with macular corneal dystrophy. AB - Human serum sulfotransferase activities were measured in normal controls and patients with macular corneal dystrophy (MCD), an inherited disorder characterized by the decreased sulfation of keratan sulfate in the corneal stroma and serum, using two kinds of acceptor: partially desulfated keratan sulfate and a trisaccharide with a GlcNAc residue at the nonreducing terminal, GlcNAcbeta1 3Galbeta1-4GlcNAc. When partially desulfated keratan sulfate was used as the acceptor, only sulfotransferase activity which transfers sulfate to position 6 of the Gal residues was detected. In contrast, when GlcNAcbeta1-3Galbeta1-4GlcNAc was used as the acceptor, sulfotransferase activity which transfers sulfate to position 6 of the nonreducing terminal GlcNAc residue could be detected. Although keratan sulfate levels in the sera of MCD patients determined by ELISA were much lower than those in normal controls, there were no detectable differences in either the sulfotransferase activity responsible for the sulfation of position 6 of Gal residues or that responsible for the sulfation of position 6 of nonreducing end GlcNAc residues between normal controls and MCD patients. These results suggest that the sulfotransferase involved in the sulfation of keratan sulfate, which is assumed to be deficient in MCD patients, may not be secreted into the serum, and that direct measurement of the sulfotransferase activity present in affected tissues such as the cornea instead of serum may be necessary to confirm the postulated deficiency in the biosynthesis of keratan sulfate in MCD. PMID- 9990122 TI - Purification, characterization, and sequence determination of phospholipase D secreted by Streptoverticillium cinnamoneum. AB - Phospholipase D (PLD), secreted into the culture medium of an actinomycete, Streptoverticillium cinnamoneum, has been purified to homogeneity and characterized. The Stv. cinnamoneum PLD efficiently catalyzes both the hydrolysis and transphosphatidylation of various phospholipids, including phosphatidylethanolamine (PE), phosphatidylcholine (PC), and phosphatidylserine (PS). However, the substrate specificity differs between the two reactions; PE serves as the most preferred substrate for the hydrolysis, but PC and PS are better substrates than PE for the transphosphatidylation. In addition, the transphosphatidylation but not the hydrolysis of PE and PC is markedly activated on the addition of metal ions, especially Al3+. Nucleotide and amino acid sequence determination of the Stv. cinnamoneum PLD revealed the presence of common structural motifs identified in all PLD sequences from various species. PMID- 9990123 TI - Time-resolved measurements of photovoltage generation by bacteriorhodopsin and halorhodopsin adsorbed on a thin polymer film. AB - We constructed a time-resolved photovoltage measurement system and examined the photovoltage kinetics of wild-type bacteriorhodopsin, its D96N mutant, and halorhodopsins from Halobacterium salinarum and Natronobacterium pharaonis. Upon illumination with a laser flash, wild-type bacteriorhodopsin showed photovoltage generation with fast (10-100 micros range) and slow (ms range) components while D96N lacked the latter, as reported previously [Holz, M., Drachev, L.A., Mogi, T., Otto, H., Kaulen, A.D., Heyn, M.P., Skulachev, V.P., and Khorana, H.G. (1989) Proc. Natl. Acad. Sci. USA 86, 2167-2171]. In contrast, photovoltage generation in halorhodopsins from H. salinarum and N. pharaonis was significant only in the ms time range. On the basis of the photovoltage kinetics and photocycle, we conclude that major charge (chloride) movements within halorhodopsin occur during the formation and decay of the N intermediate in the ms range. These observations are discussed in terms of the "Energization-Relaxation Channel Model" [Muneyuki, E., Ikematsu, M., and Yoshida, M. (1996) J. Phys. Chem. 100, 19687-19691]. PMID- 9990124 TI - Characterization of the interaction of hemolytic lectin CEL-III from the marine invertebrate, Cucumaria echinata, with artificial lipid membranes: involvement of neutral sphingoglycolipids in the pore-forming process. AB - The hemolytic lectin, CEL-III, is a Ca2+-dependent, galactose/N acetylgalactosamine-specific lectin purified from the marine invertebrate, Cucumaria echinata (Holothuroidea). After binding to specific carbohydrates on the erythrocyte surface, CEL-III forms ion-permeable pores by oligomerizing in the membrane, which leads to colloid osmotic rupture of the cells. When incubated with liposomes composed of total lipids from the human erythrocyte membrane, CEL III efficiently induced the leakage of carboxyfluorescein (CF) trapped in the vesicles, suggesting the presence of its receptor in the membrane lipids. The rate of CF-leakage increased with increasing temperature, although the hemolytic activity of CEL-III had been found to be much higher at lower temperatures (around 10 degrees C). Identification of the receptor for CEL-III was performed by examining the ability of individual lipids from human erythrocytes to induce CF-leakage from DOPC-liposomes. As a result, the most effective receptor was found to be lactosyl ceramide (LacCer), while globoside (Gb4Cer) also showed slight induction of CF-leakage. On the other hand, a binding assay involving CEL III-horseradish peroxidase conjugate indicated that CEL-III exhibits similar affinity for LacCer and Gb4Cer, suggesting that the structure or length of the carbohydrate portion of sphingoglycolipids is also relevant as to their ability to induce CF-leakage in addition to their affinity. Electron micrographs of CEL III-treated liposomes revealed that CEL-III induced considerable morphological changes in the vesicles, while a clearly distinguishable oligomeric structure of the protein was not observed. PMID- 9990125 TI - Mechanism for the recognition and activation of substrate in medium-chain acyl CoA dehydrogenase. AB - The mechanism underlying the recognition and activation of the substrate for medium-chain acyl-CoA dehydrogenase (MCAD) was spectroscopically investigated using 3-thiaacyl-CoAs as substrate analogs. The complex of MCAD with 3 thiaoctanoyl-CoA (3-thia-C8-CoA) exhibited a charge-transfer (CT) band with a molar extinction coefficient of epsilon808 = 9.1 mM-1.cm-1. With increasing 3 thiaacyl-chain length, the CT-band intensity of the complex decreased concomitantly with changes in the FAD absorption at 416 and 482 nm, and no CT band was detected in complexes with chain-lengths longer than C15. Detailed analysis of the absorption spectra suggested that the complexed states represent a two-state equilibrium between the CT-inducing form and the CT-non-inducing form. 13C-NMR measurements with 13C-labeled ligand clarified that 3-thia-C8-CoA is complexed to MCAD in an anionic form with signals detected at 163.7 and 101.2 ppm for 13C(1) and 13C(2), respectively. In the MCAD complex with 13C(1)-labeled 3-thia-C12-CoA, two signals for the bound ligand were observed at 163.7 and 198.3 ppm, and assigned to the anionic and neutral forms, respectively. Only the neutral form signal was measured at 200.6 ppm in the complex with 13C(1)-labeled 3-thia-C17-CoA. These results indicate that the CT band can be explained in terms of an internal equilibrium between anionic (CT-inducing) and neutral (CT-non inducing) forms of the bound ligand. Resonance Raman spectra of the MCAD.3-thia C8-CoA complex, with excitation at the CT band, showed enhanced bands, among which the 854- and 1,368-cm-1 bands were assigned to the S-C(2) stretching mode of the ligand and to flavin band VII, respectively. Since the enhanced bands were observed at the same wave numbers in complexes with C8, C12, and C14-ligands, it appears that the CT-inducing form shares a common alignment relative to oxidized flavin irrespective of differences in the acyl-chain length. However, with longer ligands, the degree of resonance enhancement of the Raman bands decreased in parallel with the CT-band intensity; this is compatible with the increase in the CT-non-inducing form in complexes with longer ligands. Furthermore, the pH dependence of the CT band gave an apparent pKa = 5.6-5.7 for ligands with chain lengths of C8-C12. The NMR measurements revealed that, like chain-length dependence, the pH dependence can be explained by a two-state equilibrium derived from the protonation/deprotonation of the CT-inducing form of the bound ligand. On the basis of these results we have established a novel model to explain the mechanism of recognition and activation of the substrates/ligands by MCAD. PMID- 9990126 TI - Influence of chondroitin sulfate charge density, sulfate group position, and molecular mass on Cu2+-mediated oxidation of human low-density lipoproteins: effect of normal human plasma-derived chondroitin sulfate. AB - The effects of chondroitin sulfate samples with decreasing charge densities, different 4-sulfate/6-sulfate ratios, and various molecular masses on Cu2+ induced oxidation of human low-density lipoprotein (LDL) were evaluated by monitoring conjugated diene formation and the tryptophan fluorescence kinetics. Low-sulfated chondroitin sulfate (CS) from beef trachea had a very strong protective antioxidant effect. Quite similar behavior was observed for CS from pig trachea, and a fructose-containing polysaccharide with a chondroitin backbone from Escherichia coli was also strongly protective as to LDL oxidation. CS samples with decreasing charge densities proved effective in inhibiting LDL oxidation. A totally desulfated sample still exhibited a great capacity to protect LDL against oxidation. CS-4-sulfate samples (sulfate to carboxyl ratio of 0.62, about 65% 4-sulfate groups and 5% 6-sulfate groups) retained great ability to inhibit the Cu2+-mediated human LDL oxidation. CS fractions with different molecular masses were examined as possible inhibitors of LDL oxidation. Samples with molecular masses lower than about 8,570 (13-15 disaccharide units) were unable to protect human LDL from Cu2+-induced oxidation. Similar results were obtained on studying the degradation of tryptophan residues of the LDL protein moiety resulting from Cu2+ complexation through amino acid residues. A low sulfated CS (sulfate to carboxyl ratio of 0.41, a molecular mass of about 15,600) having effective anti-oxidant properties as to metal-induced LDL oxidation was isolated from normal human plasma. The protective capacity as to Cu2+-mediated LDL oxidation of CS is discussed in relation to its structure, also considering the physiological role of plasma CS in relation to factors that can alter its properties. PMID- 9990127 TI - Comparison of the apoptotic pathways induced by L-amino acid oxidase and hydrogen peroxide. AB - We have found that L-amino acid oxidase (LAO) induces apoptosis in several cultured cell lines by generating H2O2 [Suhr, S.M. and Kim, D.S. (1996) Biochem. Biophys. Res. Commun. 224, 134-139]. It is demonstrated in the present work that the LAO-induced apoptotic mechanism is clearly distinguished from the one stimulated directly by exogenous H2O2. MOLT-4 cells undergo somewhat different morphological changes depending on the apoptotic inducer, LAO or H2O2. LAO induced apoptosis can be protected by the antioxidant N-acetylcysteine or the free radical scavenger melatonin, while H2O2-induced apoptotic cell death is not protected. A caspase inhibitor, acetyl-Tyr-Val-Ala-Asp-aldehyde (ac-YVAD aldehyde), prevents cell death when the apoptosis is induced by exogenous H2O2. On the other hand, the ac-YVAD-aldehyde tetrapeptide inhibitor that is dominantly effective on interleukin-1beta converting enzyme failed to block the apoptotic event initiated by LAO. Several lines of experimental evidence suggest that apoptotic cell death induced by LAO is not due solely to the hydrogen peroxide produced by the enzymatic reaction. PMID- 9990128 TI - Structure analysis of a collagen-model peptide with a (Pro-Hyp-Gly) sequence repeat. AB - The crystal structure of a triple helical peptide (Pro-Hyp-Gly)10 has been determined at 1.9 A resolution. Single crystals grown by the hanging drop method, diffracted to a resolution of 1.8 A. The polymer-like structure of the triple helical repeat Pro-Hyp-Gly was in accordance with the 7/2 model proposed for collagen and very similar to the previously determined structure with a Pro-Pro Gly sequence repeat. The solvent structure was also very similar to that previously observed, showing similar hydration patterns, but different crystal packing. The presence of hydroxyproline did not have any effect on the molecular structure or the hydration structure. This is in accordance with the recent finding that the inductive effect of the hydroxyl group attached to the Cgamma atom of hydroxyproline enhances collagen stability rather than the extensive water network. PMID- 9990129 TI - Complete inhibition of mouse macrophage-derived foam cell formation by triacsin C. AB - Primary mouse peritoneal macrophages effectively take up and metabolize phosphatidylcholine/cholesterol liposomes containing a small amount of phosphatidylserine, which results in the massive accumulation in the cytoplasm of oil red O positive lipid droplets consisting of cholesteryl ester (CE) and triacylglycerol (TG) [Nishikawa et al. (1990) J. Biol. Chem. 265, 5226-5231]. A number of inhibitors of CE synthesis have been reported, but their effects on the lipid droplet formation have not been fully examined. Furthermore, the contribution of TG synthesis to lipid droplet formation has been poorly investigated. We have investigated the relationship between CE and TG syntheses and cytosolic lipid droplet formation in macrophages cultured in the presence of inhibitors with different modes of action. When macrophages were cultured with liposomes and [14C]oleic acid in the presence of triacsin C, a potent inhibitor of long chain acyl-CoA synthetase, both [14C]CE and [14C]TG syntheses were inhibited to similar extents with IC50 values of 0.19 and 0.10 microM, respectively. On the other hand, pregnenolone, a well-known inhibitor of cellular cholesterol transport, and CL-283,546, a potent inhibitor of acyl-CoA:cholesterol acyltransferase, inhibited [14C]CE synthesis specifically with IC50 values of 5.0 and 0.038 microM, respectively. Microscopic observation revealed that the inhibitors of cholesterol metabolism produce only a partial decrease in cytosolic lipid droplets even at the highest doses which cause almost complete inhibition of [14C]CE synthesis. However, the triacsin C-dose dependent inhibition of lipid droplet formation was almost complete at 0.59 microM, a concentration that inhibits [14C]CE and [14C]TG syntheses by about 90%. These results show that inhibiton of acyl-CoA synthetase by triacsin C causes a decrease in the cellular levels of acyl-CoA, the common substrate for CE and TG syntheses, leading to an inhibiton of neutral lipid synthesis and eventually to the complete disappearance of cytosolic lipid droplets from macrophages. These findings suggest that TG synthesis, as well as CE synthesis, is responsible for macrophage-derived foam cell formation, and is therefore a potential target for new antiatherosclerotic agents. PMID- 9990130 TI - Cell-free expression of two single-chain monoclonal antibodies against lysozyme: effect of domain arrangement on the expression. AB - Single-chain antibodies (scFv), which can be produced in Escherichia coli cells, have been shown in numerous cases to be active in antigen binding. In the case of the two anti-lysozyme single-chain antibodies, scFvLH and scFvHL, which have the reversed arrangement of the variable domains of the heavy and light chains of the corresponding monoclonal antibodies, the expression level differs greatly when they are produced in Escherichia coli [Tsumoto et al. (1995) Biochem. Biophys. Res. Commun. 201, 546-551]. Although the expression level of scFvLH is high in vivo, the single chain antibody with the reversed orientation (scFvHL) was synthesized in a very low yield and no active product could be obtained. We report here the synthesis of these two anti-lysozyme single-chain antibodies in high yields and with high biological activities in a cell-free E. coli expression system in the presence of reduced and oxidized glutathione, protein disulfide isomerase (PDI), and chaperones. In immunological blotting assays, the synthesized scFvs with both arrangements exhibit specific binding activity to the corresponding antigens, hen egg-white lysozyme, and in an activity assay both inhibited the action of lysozyme. scFvLH is synthesized mainly as a product with the expected molecular weight, whereas scFvHL is produced with additional shorter fragments, suggesting that the low yield isolation through the expression in vivo is due to mistranslation or ribonucleolytic cleavage of the transcript. In the cell-free expression of scFv a certain amount of the product is precipitated but in the presence of chaperones the amount of soluble protein increased from 25 to 90% (PDI and chaperones). The overall expression level and the specific biological activity, however, were hardly influenced. The system reported here can provide significant amounts of various scFv fragments regardless of the order of variable regions, including those which are hardly expressed in vivo. PMID- 9990131 TI - Localization of 17-kDa myosin light chain isoforms in cultured aortic smooth muscle cells. AB - Smooth muscle myosin II contains two 17-kDa essential light chain isoforms (LC17gi and LC17nm) of which the relative contents differ among myosins. To understand the roles of LC17 isoforms in the functions of myosin, we performed an immunofluorescence microscopic examination of their localization in primary cultured cells isolated from rat aortic smooth muscle. To identify the isoforms, rabbit polyclonal antibodies were prepared against C-terminal nonapeptides corresponding to either LC17gi or LC17nm from porcine aortic smooth muscle myosin. These isoforms differ in only 5 amino acid residues within the C-terminal 9 residues. These antibodies specifically recognize each LC17 isoform on urea PAGE of total rat aortic cell lysates. Immediately after plating, the smooth muscle cells stained heterogeneously with each antibody, indicating differing contents of LC17 isoforms among cells. On double staining 1-2 d cultures with both antibodies, LC17nm was detected diffusely throughout the cytoplasm, whereas LC17gi was concentrated in specific regions such as the cell periphery and the base of cytoplasmic processes. These results support the suggestion that myosin containing LC17gi is essential for force-generation by aortic smooth muscle and that myosin containing LC17nm may play an important role in maintaining smooth muscle tension. PMID- 9990132 TI - High performance in refolding of Streptomyces griseus trypsin by the aid of a mutant of Streptomyces subtilisin inhibitor designed as trypsin inhibitor. AB - Refolding of reduced and denatured Streptomyces griseus trypsin (SGT) was investigated. In the standard buffer of 50 mM Tris-HCl, the refolding yield of 1 microg/ml of SGT did not exceed 15%. This low yield was assumed to be due mainly to autoproteolysis and/or aggregation occurring concurrently with refolding. On the basis of this assumption, SGT was immobilized on agarose gel in order to suppress such intermolecular interactions, and various refolding media were examined for their ability to minimize misfolding. As a result, 1 M Tris, 1 M diethanolamine, and 1 M triethanolamine were chosen, and their application to the solution system increased the refolding yield considerably, to ca. 45%. A further dramatic increase in yield, to 85%, was observed when a mutant Streptomyces subtilisin inhibitor (SSI, C71SM73KC101S), engineered as a temporary inhibitor of SGT, was added to the solution system to suppress autoproteolysis during refolding. The application of a temporary inhibitor may be greatly effective in not only improvement of yield but also selection of media for the refolding of protease. PMID- 9990133 TI - Human renin-binding protein is the enzyme N-acetyl-D-glucosamine 2-epimerase. AB - The existence of human renin-binding protein (RnBP) in the kidney has been shown by the isolation and characterization of a complex of porcine renin-human RnBP [S. Takahashi et al. (1985) J. Biochem. 97, 671-677]. However, the properties of the free form of human RnBP had not been understood, because of the limitation of materials. In the present study, we have expressed human RnBP in Escherichia coli JM 109 cells under the transcriptional control of taq promoter and purified it by conventional column chromatographies. The purified recombinant human RnBP (rhRnBP) exists as a dimer and inhibits porcine renin activity through formation of a complex of porcine renin with rhRnBP, the so-called high-molecular-weight renin. Moreover, the rhRnBP catalyzes the interconversion between N-acetyl-D glucosamine (GlcNAc) and N-acetyl-D-Mannosamine (ManNAc) with the apparent Km values of 21.3 mM for GlcNAc and 12.8 mM for ManNAc, and 0.13 mM for effector ATP. ATP is essential for the GlcNAc 2-epimerase activity of human RnBP. These results indicate that the human RnBP is a GlcNAc 2-epimerase. PMID- 9990134 TI - Identification of trimeric myosin phosphatase (PP1M) as a target for a novel PKC potentiated protein phosphatase-1 inhibitory protein (CPI17) in porcine aorta smooth muscle. AB - CPI17, a phosphorylation-dependent inhibitory protein of protein phosphatase-1 (PP1), is dominantly expressed in smooth muscle, and the inhibitory activity is potentiated by protein kinase C and its related enzymes [Eto, M. et al. (1997) FEBS Lett. 410, 356-360]. In order to identify its physiological target in smooth muscle, the myofibrillar extract from porcine aorta media was analyzed by affinity chromatography on CPI17-conjugated Sepharose. The binding of phosphatases to the resin depended on thiophosphorylation of CPI17, and about 90% of the phosphatase activities toward phosphorylated myosin (p-myosin) and phosphorylase-a were bound to the resin and could be eluted with 0.5 M NaCl. The IC50 values of thiophosphorylated CPI17 toward phosphatases bound to the resin were in the range of 0.5-3 nM, as expected for the PP1 holoenzymes sensitive to CPI17. The CPI17-sensitive fraction was further separated into several peaks of phosphatase activity by column chromatography on Mono Q, which suggested multiple functions of CPI17 as a mediator of the protein kinase C-related signal transduction pathway in aorta smooth muscle. The major activity toward p-myosin was identified as the myofibril-bound PP1 (PP1M), and its subunit composition (140, 37, and 20 kDa) was consistent with that of PP1M from chicken gizzard and porcine bladder. The purified PP1M was completely inhibited by phosphorylated and thiophosphorylated CPI17. Kinetic analysis showed mixed inhibition of PP1M by CPI17 (Ki = 1.9 nM and Ki' = 5.1 nM). The concentration of CPI17 in aorta smooth muscle cells was estimated to be at least 0. 3 microM from the result of Western analysis. This concentration appears to be sufficient to suppress the in situ PP1M in aorta smooth muscle, and PP1M is thus identified as a target of CPI17 in vascular smooth muscle. PMID- 9990135 TI - Partial purification and characterization of a novel endo-beta-mannosidase acting on N-linked sugar chains from Lilium longflorum thumb. AB - An enzyme catalyzing the hydrolysis of the Manbeta1-4GlcNAc linkage of N-linked sugar chains was partially purified and characterized. Endo-beta-mannosidase activity was detected using pyridylaminated (PA-) Manalpha1-6Manbeta1 4GlcNAcbeta1-4GlcNAc as the substrate in a homogenate of lily flowers (Lilium longflorum Thumb). The enzyme was partially purified by ammonium sulfate precipitation, and Q-Sepharose, Superdex 200, hydroxyapatite, Poros PE/M, Mono Q, and Superdex 200 column chromatographies. The optimum pH was 5.0 and the estimated molecular weight of the enzyme was 78,000, as determined by gel filtration. The Km value found for Manalpha1-6Manbeta1-4GlcNAcbeta1-4GlcNAc-PA was 1.4 mM. The enzymatic activity was not influenced by the addition of 10 mM EDTA or 2 mM Ca2+. Experiments on the hydrolysis of several PA-N-linked sugar chains revealed that the enzyme hydrolyzed MannManalpha1-6Manbeta1-4GlcNAcbeta1 4GlcNAc-PA (n = 0-2) into a mixture of MannManalpha1-6Man and GlcNAcbeta1-4GlcNAc PA, indicating that it is an endoglycosidase in nature. However, the enzyme did not hydrolyze beta1-4mannohexaose or p-nitrophenyl beta-mannopyranoside. PMID- 9990136 TI - Purification and characterization of a novel vascular endothelial cell growth inhibitor secreted by macrophage-like U-937 cells. AB - A human histiocytic lymphoma cell line, U-937 cells, secretes several vascular endothelial cell growth inhibitors including leukemia inhibitory factor, oncostatin M, tumor necrosis factor-alpha, and transforming growth factor-beta1. Characterization of partially purified fractions from the conditioned media of phorbol ester-treated U-937 cells suggested the existence of unknown endothelial growth inhibitors. Using a combination of copper affinity, heparin affinity, cation exchange, and reversed phase liquid chromatographies, a growth inhibitor for endothelial cells was purified to homogeneity from conditioned media. The purified growth inhibitor migrated as a 65 kDa band on SDS-polyacrylamide gel electrophoresis under both reducing and nonreducing conditions. Microsequencing analyses of the tryptic fragments of the growth inhibitor and a BLAST search analysis revealed a unique sequence showing no homology to known proteins. The purified protein inhibited endothelial cell growth in a dose-dependent manner, but had no effect on smooth muscle cell growth. The factor also blocked endothelial cell growth induced by both fibroblast growth factor-2 and vascular endothelial growth factor, and was additively effective in inhibiting the growth of endothelial cells by U-937 cell-derived endothelial cell growth inhibitors. Thus, this factor appears to be a novel inhibitor with specificity for vascular endothelial cells, and is tentatively called endothelial cell inhibitor (ECI) in this study. PMID- 9990137 TI - Isolation and amino acid sequence of a phospholipase A2 inhibitor from the blood plasma of the sea krait, Laticauda semifasciata. AB - A phospholipase A2 (PLA2) inhibitor was purified from the blood plasma of a sea krait, Laticauda semifasciata, by sequential chromatography on Sephadex G-200, Mono Q, and Phenyl Sepharose columns. The purified inhibitor was found to be the same type as the PLA2 inhibitors, named PLIgamma, that had been purified from the blood plasma of the Thai cobra Naja naja kaouthia [Ohkura et al. (1994) Biochem. Biophys. Res. Commun. 200, 784-788] and Chinese mamushi Agkistrodon blomhoffii siniticus [Ohkura et al. (1997) Biochem. J. 325, 527-531]. Like other PLIgammas, the L. semifasciata inhibitor (LsPLIgamma) inhibited equally all of the PLA2s investigated including Elapid venom PLA2s (group I), Crotalid and Viperid venom PLA2s (group II), and honeybee PLA2 (group III). The LsPLIgamma was a 100-kDa glycoprotein composed of two distinct subunits, LsPLIgamma-A and LsPLIgamma-B, with an approximate molar ratio of 2:1. The amino acid sequences of the two subunits were determined by alignment of the peptides obtained by lysyl endopeptidase, endoproteinase Asp-N, and staphylococcal V8 protease digestions. LsPLIgamma-A and LsPLIgamma-B were composed of 182 and 181 amino acid residues, respectively; and the former subunit was a glycoprotein containing one asparagine linked sugar chain at the position 157. The sequences of LsPLIgamma-A and LsPLIgamma-B showed 65 and 74% homology, respectively, to those of the corresponding subunits of N. naja kaouthia PLIgamma, and had two tandem patterns of cysteine residues, characteristic of the urokinase-type plasminogen activator receptor (uPAR) and members of the Ly-6 superfamily. PMID- 9990138 TI - In vitro and in vivo effects of phenolic antioxidants against cisplatin-induced nephrotoxicity. AB - We have investigated the effect of phenolic antioxidants on cisplatin-induced cytotoxicity in vero (African Green Monkey Kidney) cells and in rat renal cortical slices in vitro, and on cisplatin-induced nephrotoxicity in rats in vivo. Incubation of cisplatin with vero cells resulted in time- and concentration dependent cytotoxicity, as characterized by decreased tryphan blue exclusion (TBE) and increased release of lactate dehydrogenase (LDH) into the medium. Cisplatin also caused reduction of glutathione (GSH) in a concentration-dependent manner. In the rat renal cortical slices model, incubation of cisplatin for 120 min caused an increase in malondialdehyde (MDA), a decrease in GSH and inhibited p-aminohippurate (PAH) uptake in a concentration-dependent manner. Among phenolic antioxidants, isoeugenol (IG) was found to be more active against cisplatin induced cytotoxicity in vero cells as well as in rat renal cortical slices than eugenol (EG) and dehydrozingerone (DZ). However none of the test compounds were able to arrest the reduction of the GSH content induced by cisplatin in either the vero cells or the renal cortical slice model. Administration of cisplatin (3 mg/kg) i.p. to rats resulted in significant reduction of body weight, and elevation of blood urea nitrogen (BUN) and serum creatinine. Treatment with IG 10 mg/kg i.p. 1 h before cisplatin resulted in partial but significant protection against the cisplatin-induced reduction of body weight, and elevation of BUN and serum creatinine, the protection being 34, 46, and 62%, respectively. EG and DZ (10 mg/kg, i.p.) were found to be inactive in vivo. Because IG is a potent free radical scavenger and protects against cisplatin-induced toxicitiy, the present results have many clinical implications in chemotherapy and thus warrants further investigation. PMID- 9990139 TI - Double-stranded RNA-activated protein kinase (PKR) fused to green fluorescent protein induces apoptosis of human embryonic kidney cells: possible role in the Fas signaling pathway. AB - PKR is an interferon-inducible, double-stranded (ds) RNA-activated serine/threonine protein kinase, and has been shown to play roles in viral pathogenesis, cell growth and apoptosis. We expressed PKR as a fusion protein with enhanced jellyfish green fluorescence protein (EGFP) in human embryonic kidney 293 cells to visualize the effect of PKR transfection. The EGFP-fusion construct with wild-type PKR showed both auto- and substrate-phosphorylation activities independent of dsRNA, indicating EGFP-PKR is constitutively active. The EGFP-construct with a mutant PKR with the first RNA binding domain deleted still possessed kinase activities. On the other hand, the EGFP-fusion with a catalytically inactive mutant of PKR with the substitution of K at 296 with R, which has been shown to have tumorigenic properties, did not possess kinase activities. Transfection of the constitutive active forms of EGFP-PKR constructs induced apoptosis in 293 cells without dsRNA, whereas the EGFP-fusion with the catalytically inactive mutant did not cause apoptosis but rather protected cells from Fas-induced cell death. In addition, Fas-stimulation increased endogenous PKR activities. These results constitute evidence that PKR is sufficient to induce apoptosis, and plays a role in Fas-mediated apoptosis. PMID- 9990140 TI - The stabilized structural array of two HMG1/2-boxes endowed by a linker sequence between them is requisite for the effective binding of HMG1 with DNA. AB - High mobility group (HMG) protein 1 contains two DNA binding motifs, called HMG1/2-boxes, linked with a linker region. The functional relationships between the two boxes and the mechanism of involvement of the linker region for effective binding of HMG1 were examined. The binding analyses of truncated HMG1 peptides with DNA indicated that the structural array of two boxes stabilizes the interaction of HMG1 with DNA. The mutation analyses of the linker region suggested that the region is equipped with tolerance for the deletion of a few amino acid residues to allow appropriate binding of the two boxes with DNA, and that the basic cluster in the linker sequence is in a position to interact with DNA. The existence of tolerance for the linker sequence was found to be conserved during the evolution of HMG1 protein homologues. A structural model for array of two boxes associating with DNA minor groove was constructed on the basis of the experimental results and energy minimization. The model proposes that the DNA binding region in HMG1 covers an 18 bp DNA region and induces its bending by about 140 degrees. The linker region may function to maintain the structural array of two HMG1/2-boxes by direct interaction with DNA. PMID- 9990141 TI - Basement membrane heparan sulfate proteoglycan (perlecan) synthesized by ACC3, adenoid cystic carcinoma cells of human salivary gland origin. AB - The biosynthesis of basement membrane heparan sulfate proteoglycan (HSPG), known as perlecan, in ACC3 cells established from a adenoid cystic carcinoma of the human salivary gland was studied using metabolic labeling and immunoprecipitation with discriminative antibodies specific for HSPG core protein. Treatment of immunoprecipitated HSPG with HNO2, heparitinase, and chondroitinase ABC revealed that ACC3 cells synthesized HSPG molecules composed of 470-kDa core protein and heparan sulfate but not of chondroitin sulfate. The core protein was shown to contain complex type N-linked oligosaccharides by digestion with N-glycanase and endoglycosidase H. Pulse-chase experiments showed that the mature form of HSPG was formed in the cells in 30 min and released into the medium thereafter. Degradation of HSPG was also found in the chase period of 3 h. In time course experiments, HSPG was found to be synthesized maximally at day 4 after plating, deposited in the cell layer maximally at day 6, and secreted maximally at day 8. This was also confirmed by immunofluorescence, Northern blotting, and in-situ hybridization. The results indicate that ACC3 cells synthesize, secrete and degrade basement membrane type HSPG, which is analogous to those produced by other cell types, and that the biosynthesis and secretion of HSPG in ACC3 cells are strictly regulated by the cell growth, that may be reflected in the characteristic histology of adenoid cystic carcinomas. PMID- 9990142 TI - Properties of the V0V1 Na+-ATPase from Enterococcus hirae and its V0 moiety. AB - We report here the large-scale purification of vacuolar (V0V1)-type Na+-ATPase from Enterococcus hirae achieved using column anion-exchange and gel filtration chromatographies; 32 mg of purified enzyme comprising nine subunits, A, B, C, D, E, F, G, I, and K, was obtained from 20 liter culture. This amount is 500-fold larger than that reported in the previous paper [Murata, T., Takase, K., Yamato, I., Igarashi, K., and Kakinuma, Y. (1997) J. Biol. Chem. 272, 24885-24890]. The purified enzyme shows a high specific activity of ATP hydrolysis (35.7 micromol Pi released/min/mg protein). ATP-driven 22Na+ uptake by reconstituted V0V1 proteoliposomes exhibited an apparent Kt value for Na+ of 40 microM, which is near the Km value (20 microM) for Na+ of the ATP hydrolytic activity. Denatured gel electrophoresis revealed that six subunits, A, B, C, D, E, and F, are releasable as the V1 subunit from the V0V1 complex by incubation with ethylenediaminetetraacetic acid; subunit G was not identified. The remaining V0 liposomes containing I and K subunits catalyzed Na+ uptake in response to potassium diffusion potential (Deltapsi, inside negative); the Kt value for Na+ of this reaction was estimated to be about 2 mM. Inhibition by N,N' dicyclohexylcarbodiimide (DCCD) of the Na+-ATPase activity and Deltapsi-driven Na+ uptake by the V0-liposomes was prevented by the presence of Na+, suggesting that the Na+ binding site overlaps with the DCCD-reactive site. PMID- 9990143 TI - Molecular structure of the amyloid-forming protein kappa I Bre. AB - The molecular structure of the amyloid-forming Bence-Jones protein kappa I Bre has been determined by X-ray crystallography at 2.0 A resolution. The fragment from the kappa chain of immunoprotein contains 107 amino acid residues, and polymerizes in the crystal form into a giant helical spiral, surrounding a cylinder of water 50 A in diameter with a repeat of 77.56 A, containing 12 kappa molecules, plus another 12 molecules from neighboring parallel spirals. The resulting structure has many features which have been found or suggested from studies on the protein fibrils found in amyloid deposits. From the results of the X-ray crystal structure a hypothesis is presented for the structure and formation of the amyloid fibril. PMID- 9990144 TI - A reevaluation of nystatin in prophylaxis and treatment of oropharyngeal candidiasis. AB - The incidence of oropharyngeal candidiasis is growing. The species of the genus Candida are extremely frequent among human colonizers. The changes in the yeast human interaction by aging, debilitating, and immunosuppressive diseases, and the more aggressive medical interventions can explain this phenomenon. Antifungals are used both in prophylaxis and therapy, but the number of available agents remains scarce. Acquired resistance to the more commonly used antifungal agents, the azole compounds, is also an increasing threat, Policies for antifungal use should be established in order to maintain the therapeutic possibilities of the current compounds, The widespread use of systemic azoles, agents useful in deep mycosis, may increasingly exert a selective power for resistant variants. Superficial infections, such as oropharyngeal candidiasis, can be successfully controlled by nystatin, a classic polyene, which is very well tolerated and has very low rates of resistance. This review on the importance of oropharyngeal candidiasis emphasizes this therapeutic possibility, and is complemented by in vitro studies documenting the excellent activity of nystatin on both azole susceptible and resistant strains. PMID- 9990145 TI - [Characteristics of Helicobacter pylori infection in children: therapeutic implications]. PMID- 9990146 TI - [The effect of a rational and consensual protocol for the use of ceftriaxone in a general hospital]. AB - In hospitals in Spain there has been a large increase in the use of wide spectrum antibiotics. The objective of this study was to evaluate the influence of a rational, consensual protocol on the use of ceftriaxone. An observational and prospective study was carried out using information provided by the Servicio de Farmacia on the in-hospital prescriptions for ceftriaxone. The study included two groups as follows: a control group (October-December 1995) not taking into account the protocols for antibiotic treatment; and a study group in the same months in 1996 with the consensual protocols taken into account. The criteria for the type of patient, infection, evolution and antibiotic treatment were evaluated according to the criteria in the international literature on this type of study. The initial characteristics of both groups of patients were similar. Following the use of the protocol there was a significantly associated reduction in use (48 cases in the study group vs. 57 cases in the control group), an increase in the appropriate use (31. 57% in the control group vs. 75% in the study group), an increase in the cure rate (70.17% in the control group vs. 91.7% in the study group) and a decrease in hospital stay of 7.53 days (22.59 days in the control group vs. 15.06 in the study group), producing a savings per cured patient of 617.142 pesetas. It was concluded that the consensual protocol and its proper application make for a highly interesting approach given that it allowed for better quality use of ceftriaxone with greater cost-effectiveness. PMID- 9990147 TI - [Relationship between the sensitivity of Pseudomonas aeruginosa and the post antibiotic effect of sparfloxacin and ciprofloxacin]. AB - The post antibiotic effect (PAE) of 8 strains of Pseudomonas aeruginosa with different susceptibility to sparfloxacin and ciprofloxacin was evaluated by the colony counting method using centrifugation to remove the antibiotic. The bacteria were exposed for 60 min to a quinolone concentration of 1 mg/ml. The MIC of sparfloxacin and ciprofloxacin ranged from 0.25-256 mg/ml and from 0. 25-128 mg/ml, respectively. PAE values ranged from 46 8.71 to 59.6 2.51 min and from 46.33 15.2 to 62.6 3.70 min, respectively. No significant statistical differences were found in the PAE duration for quinolones nor between strains. No correlation could be established between PAE and susceptibility of P. aeruginosa to quinolones. PMID- 9990148 TI - [Comparison of the microdilution method (PASCO), the Etest and disc-diffusion in streptococcus pneumoniae antibiotic susceptibility testing]. AB - MIC values and inhibition zone diameters for penicillin, cefotaxime, and erythromycin where determined in 75 consecutive Streptococcus pneumoniae blood isolates by microdilution (PASCO), disc-diffusion and Etest. Using the Etest, 40% and 29.3% of the isolates showed low- or high-level resistance to penicillin and erythromycin respectively, whereas 9.3% were intermediate to cefotaxime. No high level resistance to cefotaxime was found. No errors were found with the comparison of penicillin and cefotaxime results by microdilution and Etest, with just 2 (2.7%) and 3 (4%) minor errors appearing respectively. On the other hand, when comparing penicillin susceptibility results by disc-diffusion (1 mg oxacillin disc) and Etest, 6 (8%) major errors and 18 (24%) minor errors were found. PMID- 9990149 TI - [Activity of trovafloxacin and ten other antimicrobials against gram negative anaerobic bacilli]. AB - As an increase in anaerobes resistant to a great variety of antimicrobials have been seen in the last few years, a search for new agents with activity against these microorganisms is needed. One of these agents is trovafloxacin. In our study, all strains were susceptible to imipenem, metronidazole, chloramphenicol and piperacillin/tazobactam. A total of 97% of the strains were inhibited with 2 mg/ml of trovafloxacin. The microorganisms Bacteroides fragilis and B. uniformis showed the least susceptibility against the antimicrobials studied, with a MIC90 for trovafloxacin of 1 and 2 mg/ml, respectively. Fusobacterium spp. were the most susceptible, with an MIC90 for trovafloxacin of 0.5 mg/ml. Trovafloxacin showed good activity against Gram-negative anaerobe rods, and could therefore be considered as an alternative in the treatment of the infections produced by these microorganisms. PMID- 9990150 TI - Urinary Phenylglyoxylic Acid Excretion after Exposure to Ethylbenzene among Solvent-exposed Chinese Workers. AB - Factory surveys were conducted in the second half of work weeks on 360 solvent workers (202 men and 158 women) and 281 controls in China. Monitoring personal exposures showed that ethylbenzene exposure was low (geometric mean 1.8 ppm) and was accompanied by coexposure to toluene (1.5 ppm) and three xylene isomers (6.7 ppm). Urine samples collected at the end of the eight-hour shift were analyzed for phenylglyoxylic and mandelic acids by high-pressure liquid chromatography at 257 nm. Despite the low level of the exposures, a significant correlation was observed between ethylbenzene exposure and urinary phenylglyoxylic acid, with high (0.6-0.7) correlation coefficients, suggesting that urinary phenylglyoxylic acid is a good marker of occupational exposure to ethylbenzene. Mandelic acid also correlated with ethylbenzene exposure, but with much smaller coefficients (0.2), possibly because the method employed was more sensitive to phenylglyoxylic acid than to mandelic acid. PMID- 9990151 TI - Occupational Stress and Dysmenorrhea in Women Working in Cotton Textile Mills. AB - The authors conducted a cross-sectional study of 895 never-smoking female textile workers, aged 20-40 years, employed in three cotton textile mills in Anhui Province, China, to assess the association of self-reported occupational stress with dysmenorrhea. Stress was assessed by means of a questionnaire incorporated into a larger, general health survey of textile workers. Dysmenorrhea was defined as abdominal/pelvic pain during menses. Proportions of no/low, moderate, and high levels of occupationally-related emotional stress among all the subjects were 56%, 23%, and 21%, respectively. The overall prevalence of dysmenorrhea in the population was 59.7%. The adjusted odds ratios of dysmenorrhea for women who had moderate and high levels of occupational stress relative to those with low levels were 1.6 (95% CI:1.1-2.2) and 2.3 (95% CI:1.6-3.4), suggesting an exposure response relationship. The estimated odds ratio based on assigned scores (0, 1, and 2 assigned for no/low, moderate, and high degrees of occupational stress) was 1.5 (95% CI:1.3-1.8). In the analyses stratified by the mills and the women's job titles, a positive association was found in all groups. The association remained significant (OR = 1.6, 95% CI:1.3-2.0) when the analysis was restricted to those women with only one reported livebirth pregnancy. The findings suggest that high degrees of occupational stress predispose female textile workers to dysmenorrhea. PMID- 9990152 TI - Effects of Deomestic Gas Cooking and Passive Smoking on Chronic Respiratory Symptoms and Asthma in Elderly Women. AB - The purpose of the study was to assess the effect of indoor air pollution resulting from the use of gas stoves for cooking on women more than 65 years old, who may be more susceptible than younger women to the harmful effects of pollutants. A total of 1,544 women living in Cracow took part in a survey. The data were collected to standardized interviews dealing with respiratory symptoms (coughing, phlegm production, dyspnea on exertion), chronic chest diseases diagnosed by a doctor, active and passive smoking, educational level, type of cooking fuel used, and average time spent daily in cooking. Lung function was tested with a spirometer. Comparison of the prevalence of respiratory symptoms by daily duration of cooking of smokers with that of never-smokers showed more symptoms in smokers even in the low-exposure category. In multivariate analysis, the effects of duration of cooking with gas on asthma for the highest exposure category in terms of odds ratios (ORs) were 2.8 for the never-smokers and 2.4 for the smokers; however, passive smoking had no significant effect. As regards dyspnea on exertion, both gas cooking and passive smoking had significant effects in never-smokers (OR for gas cooking 7.2, for passive smoking 2.2). The OR for dyspnea due to cooking with gas in smokers was 3.1. Mean FVC and FEV&inf1; levels were not decreased among passive smokers or those who were subject to high levels of gas-cooking exposure. PMID- 9990153 TI - In-vitro Biological Study to Evaluate the Toxic Potentials of Fibrous Materials. AB - The potential toxicities of fibrous materials were investigated by measuring the levels of cytokines as well as cytoplasmic and lysosomal enzymes released from alveolar macrophages (AMs) in vitro. Five man-made mineral fibers (ceramic, glass, potassium octatitanate, and two magnesium sulfate whiskers), as well as five natural mineral fibers (UICC chrysotile, crocidolite, amosite, anthophylite, and Turkish erionite) were tested. Basic fiber characteristics, including fiber size, surface area, number, and solubility, were also measured. Tumor necrosis factor (TNF) production, lactate dehydrogenase (LDH) and beta-glucuronidase (BGU) release from AMs exposed to potassium octatitanate, magnesium sulfate whiskers, and ceramic fiber correlated with pathologic changes in the lung according to inhalation studies. The solubility of the man-made mineral fibers also correlated with the half-life of clearance in an in-vivo study. The results suggest that measured values of TNF production, LDH and BGU release in vitro, and fiber solubility combined are a good indicator of the pathogenic potential of fibers in vivo. PMID- 9990154 TI - Changes in Attitudes towards and Awareness of A Medical Waste Incinerator during the Facility Siting Process. AB - The authors investigated the impact of the process of siting a medical waste incinerator on knowledge and attitudes among subgroups within an adjacent community using a model of risk perception that conceptually divided the community into attitudinal and behavioral subgroups based on awareness and concern in relation to the planned facility. The study design was a one-year survey and a three-year postintervention survey conducted during the siting process. The authors also documented the siting process in order to relate siting inputs to attitudinal and knowledge changes within the community. After three years of promotion, 80% of the respondents remained unaware of the site. The authors conclude that it may be very difficult to engender awareness in affected communities and more difficult still to influence attitudes towards the proposed facility. PMID- 9990155 TI - Reversal of the Healthy-worker Effect. AB - The well-known healthy-worker effect (HWE) may become reversed at advanced ages. The HWE deficit of deaths at younger ages must be compensated for by extra deaths at advanced ages. A hypothesized distribution of these compensating deaths illustrates how they may increase age-specific mortality rates. This can probably produce spurious associations with occupational exposures when cohort follow-up is long. This point is illustrated for lung cancer by data from a reported study of beryllium workers. PMID- 9990156 TI - An International Effort to Improve Methods of Data Collection and Exposure Assessment for Community-based Case-Control Studies of Occupational Disease. AB - The authors recommend that an international effort be made to develop standardized questionnaires for collecting occupational exposure information and to develop standard assessment procedures for evaluating occupational exposures in community-based case-control studies. Such standardization should improve the quality and credibility of findings from this type of study, as well as the comparability of results across studies. PMID- 9990157 TI - Occupational Health Research in Developing Countries: The Experience in Ecuador. AB - There has been a growing volume of research regarding occupational hazards in developing countries during the past decade. Results of this work are increasingly appearing in established journals and forming part of the international database on the health effects of working conditions. However, despite many similarities to research conducted in economically advanced countries, research performed in developing countries are often quite different in their motivations, methodologies, and outcomes. To investigate these differences, the recent occupational health research experience in Ecuador was examined. Based on 15 reports that could be identified since 1980 as having sufficient information to analyze, the authors identified certain persistent themes: the preponderance of cross-sectional study designs; the limited availability of quantitative exposure measures, and the utilization of nonstandard clinical measures of outcome. Each of these limitations could be related to obvious conditions under which investigators were working, and each underscores the potential value of strategic alliances between local investigators and collaborators from developed countries. The review also documented the high importance in Ecuador to studies of "established" relationships between well-known toxicants and health. While such studies could be viewed as unoriginal or uninteresting by outsiders, they may form the basis of the domestic or regional research agenda, which cannot be overlooked or misunderstood if international collaborations are not to be exploitative. PMID- 9990158 TI - Epidemiologic Evidence of Radiofrequency Radiation (Microwave) Effects on Health in Military, Broadcasting, and Occupational Studies. AB - In this opinion piece, the author brings together and discusses the collective relevance of possible health effects of microwave or radar exposure in military, broadcasting, and occupational circumstances, with a view to assuring optimal protective practices. Sources of the information presented include 1) historical data, 2) experiences of Polish soldiers, 3) a study of U.S. naval personnel using radar in the Korean War, 4) preliminary findings of exposures to the Skrunda, Latvia, transmitter, 5) data obtained near Hawaiian broadcasting facilities, 6) occupational studies of electronic and electrical workers, including ham radio operators, 7) reproductive outcomes among physiotherapists using short-wave and microwave diathermy, and 8) U.S. foreign service personnel exposed at Embassies in Eastern Europe. Some of the data are available in the peer-reviewed literature, others in abstracts, reports, or other non-peer-reviewed forms. Some were obtained under Freedom of Information statutes and are incomplete. For some of these, there is reason to believe that further evidence desired by the investigator was not obtained. Some are case-referent studies, but most are not. Some are ecological, and all are retrospective. Few have reliable dose estimations, and none has accurate dosage information on each subject. None includes evidence of tissue heating or any short-term effect. Possible outcomes considered included 1) blood count changes, 2) evidence of somatic mutation, 3) impairment of reproductive outcomes, especially increased spontaneous abortion, and 4) increase in cancer incidence and mortality, especially of the hematopoietic system, brain, and breast. The author presents evidence that sufficient microwave exposures are associated with all four of these outcomes, concluding that the possible effects and their timings with respect to exposure are qualitatively similar to those on ionizing radiation. A prudent course of action would be to provide more protection for those exposed than required by present regulations. No systematic effort to include negative studies is made; thus this review has a positive reporting bias. PMID- 9990159 TI - Bhopal-A Case Study of International Disaster. AB - This paper outlines what is known about the probable events leading up to the disaster in Bhopal, India, in 1984, wherein release of a gas cloud from an industrial plant killed over 3,800 people. It briefly reviews the toxicology of methyl isocyanate, a major component of the cloud; presents an overview of the acute and chronic health effects of the gas exposure from published human and animal studies; identifies some of the clinical dilemmas and medical management and epidemiologic issues being debated; provides an insight into national and transnational implications; and summarizes the lessons learned or not learned from this disaster of global significance. PMID- 9990160 TI - Breast Cancer Screening among Employed American Women. AB - From the 1990 National Health Interview Survey Health Promotion and Disease Prevention supplement, the authors estimated the 1990 baseline prevalence of breast cancer screening among employed U.S. women aged 50-70 years. Proportions of women screened for breast cancer were calculated by occupational category and demographic characteristics, and were compared with the Healthy People 2000 objective that 60% of women aged 50 and older have had mammography and a clinical breast examination within the preceding two years. The objective was exceeded for white-collar workers (61.8%) and workers with some college (64.1%), but was not met by any blue-collar/service workers (40.8%); or any workers with only a high school diploma (54.7%) or less than a high school diploma (38.5%). Identification of occupational categories and demographic subgroups among working women will be helpful to those planning breast cancer screening programs, in both the public and the private sectors. PMID- 9990161 TI - Childhood Acute Lymphoblastic Leukemia: A Cluster in Southwestern Sardinia (Italy). AB - In response to public concern about an increase in the incidence of leukemia among children in southwestern Sardinia (Italy), incident cases of childhood cancer (ages 0-14) were ascertained among residents in the province of Cagliari, which comprises all of southern Sardinia, in 1974-89. Completeness of the ascertainment of leukemia cases was validated by comparison with estimates derived from official statistics of mortality and survival curves. A significant excess risk of childhood acute lymphoblastic leukemia (cALL) was found for children residing in the town of Carbonia. The risk was highest in 1983-85, when seven cases occurred versus 0.8 expected. No birth-cohort effect was observed. The cALL incidence rate was significantly higher among children born and residing in Carbonia than among children born in Carbonia but residing elsewhere. However, the cALL cases did not cluster within the town of Carbonia. The proximity of the largest industrial settlement in the region of Sardinia raised the suspicion that environmental pollution was responsible for the observed excess. Information about industrial emissions from this settlement prior to the appearance of the cALL cluster was not sufficient to reject or confirm the hypothesis. PMID- 9990162 TI - Upper-extremity Musculoskeletal Disorders in Keyboard Operators in Brazil: A Cross-sectional Study. AB - This study sought to determine the prevalence of upper-extremity musculoskeletal disorders (UEMSDs) among keyboard operators in Sao Paulo, Brazil, and to compare this prevalence with that among other office workers. One hundred and thirty keyboard operators (mean age 33 years, 60 male/70 female) and 138 office workers (mean age 35 years, 82 male/56 female) from two computing centers were interviewed by a research assistant using a standardized questionnaire. Symptomatic subjects, defined as those who reported upper extremity pain or lost work time due to pain in the preceding 12 months, were examined by a rheumatologist. Mean (SD) lengths of employment were 9 (6) years for keyboard operators and 8 (6) years for office workers. Upper-extremity pain during the preceding seven days was reported by 66 keyboard operators (51%) and by 18 office workers (13%) (p < 0.0001); during the preceding 12 months, by 90 keyboard operators (69%) and by 26 office workers (19%) (p < 0.0001). UEMSDs were diagnosed following physical examination in 50 keyboard operators and in 12 office workers (9%) (p < 0.0001). Tenosynovitis was the most common disorder diagnosed among the keyboard operators (n = 23). Among the keyboard operators the prevalence of UEMSDs was significantly lower for males (p = 0.017, OR = 0.38, 95%CI = 0.17-0.86). The presence of a diagnosed UEMSD was significantly associated with duration of employment (p = 0.005) and lack of or insufficient rest breaks (p = 0.012). Keyboard operators had significantly more UEMSDs than did office workers. Strategies aimed at the reduction of repetitive strain injuries among keyboard operators, such as the provision of adequate work breaks, should be evaluated. PMID- 9990163 TI - A Mailed-questionnaire Survey of Ex-workers: A Tool to Evaluate the Healthy worker Effect in Cross-sectional Studies. AB - In order to evaluate a possible healthy-worker effect in a cross-sectional study in a viscose rayon plant, a survey of ex-workers was conducted. From the personnel records of this factory, 475 male, Caucasian, Dutch-speaking, carbon disulfide (CS&inf2;)-exposed workers who had been employed ten years prior to the cross-sectional study were selected for study. Of these, 142 were still employed in the same plant, and 64 were deceased. Retrieval of the causes of death proved impossible. A questionnaire was mailed to the remaining 269 men, of whom 149 completed and returned it. Eighty-nine subjects reported having left the plant for health reasons. Among the health reasons specified, eye-irritation complaints were most often mentioned (53.7%), followed by gastrointestinal complaints (32.8%), complaints concerning the central nervous system (19.4%) and the peripheral nerves (11.9%), heart or lung problems (14.9%), and problems affecting the skin (9.0%). The average duration of employment decreased significantly with the intensity of the exposure to CS&inf2;. The results suggest that the findings of a cross-sectional study of current workers in the same viscose rayon plant may represent underestimates of some conditions, in particular the acute eye irritation complaints. Other complaints with high prevalences in the cross sectional study, such as complaints consistent with polyneuropathy, seemed less, while others, such as impotence, seemed not at all, subject to underestimation. PMID- 9990164 TI - Isolated Musculocutaneous Nerve Injury: A Case Report. AB - A case report of an isolated musculocutaneous nerve injury distal to the branch to the coracobrachialis muscle of the non-dominant arm is described. The injury occurred in the context of an industrial setting, specifically, an assembly plant. The non-dominant limb was injured; in contrast, most reports indicate the dominant limb was affected during strenuous activity. Nerve function was monitored with serial electromyography. Management of the injury was conservative, with eventual full functional recovery. PMID- 9990165 TI - Development and Application of a Work-process Classification. AB - Occupational exposures are related to work processes carried out by the individual worker. A classification of the work processes was developed on the basis of analyses of several databases. Work-process data were collected in a sample of Danish employees. An unambiguous, exhaustive work-process classification was developed where the work process was defined as the transformation of a work object into a product. A test showed that at least 85% of free-text data on occupational injuries contained work-process data. To illustrate applications of the classification, work-process data were used to define highly exposed and unexposed job groups. This classification may be useful for (for example) major general surveys to supplement the exposure information that job and industry classifications yield. PMID- 9990166 TI - When Science Isn't Enough: Wilhelm Hueper, Robert A. M. Case, and the Limits of Scientific Evidence in Preventing Occupational Bladder Cancer. AB - A recent outbreak of occupational bladder cancer in a Buffalo, New York, factory confirmed the carcinogenicity of ortho-toluidine, an aromatic amine that had first been implicated in human bladder cancer cases decades earlier. Events leading to this outbreak replicated the history of numerous earlier bladder cancer outbreaks among workers exposed to beta-naphthylamine and benzidine, two other aromatic amines that were widely used in the dye and rubber industries and that have been responsible for bladder cancer outbreaks in the United States, Germany, Switzerland, England, France, Italy, Austria, Czechoslovakia, the former Soviet Union, Poland, and China. The historic development of scientific knowledge of occupational bladder cancer prefigured many debates that later occurred around other environmental carcinogens; two of the giants of occupational medicine, Wilhelm Hueper and Robert A. M. Case, played seminal roles in the study of these chemicals. Examination of the history of worker exposure to aromatic amines and the subsequent development of bladder cancer at Du Pont, Allied Chemical, and other U.S. manufacturers demonstrates that these carcinogens were regulated only after cancer epidemics were recognized. Production and use of aromatic amines continues in developing countries; these nations will inevitably experience similar outbreaks unless steps are taken to eliminate exposure to these deadly chemicals. This paper chronicles the history of occupational bladder cancer in the United States, highlighting the roles of Hueper and Case in occupational cancer investigation and prevention. PMID- 9990167 TI - An Epidemiologic Study of the Effects of Carbon Disulfide on the Peripheral Nerves. AB - Although the labor inspection had disclosed considerable exposure to carbon disulfide (CS&inf2;) in a Belgian viscose rayon factory, the company medical officer had not diagnosed any case of polyneuropathy in association with CS&inf2; exposure, although this finding had been extensively reported in the literature. Personal monitoring of CS&inf2; exposure was performed in 17 jobs. Because the working conditions in the factory had not changed since 1932, a CS&inf2; cumulative exposure index (CS&inf2; index) could be calculated for each individual. Examination of the exposed subjects (n = 111) included a self administered questionnaire, a clinical neurologic examination, and electroneuromyography. Seventy-four workers from other plants, not exposed to CS&inf2; or to any other neurotoxic agent, served as referents. The average CS&inf2; exposures of the study group ranged from 4 to 112 mg/m(3). The data were analyzed with multiple regression methods, adjusting the effect of exposure for a number of possible confounders. Significant associations were found between the cumulative CS&inf2; index and symptoms consistent with polyneuropathy in the legs and with abnormal recruitment pattern and decrease of motor conduction velocities of the peroneal nerves. Exposures to CS&inf2; at levels below the present threshold limit value (31 mg/m(3)) were associated with significant decreases of motor conduction velocity. PMID- 9990168 TI - Mortality Patterns among Commercial Painters in The Netherlands. AB - In an epidemiologic study, the mortality patterns of commercial painters in The Netherlands were investigated. The hypothesis that painters are at an increased risk of cancer, especially lung cancer, was tested in collaboration with the Dutch Social Fund for painters. This fund manages the pensions of Dutch painters. In the group of painters eligible for pensions, 9,812 deaths were observed between 1980 and 1992. Proportionate mortality ratios were calculated. The results support previous findings of an increased risk of lung cancer in painters. Although no statement can be made about the actual causal agent, the authors believe that the sanding down of old paint layers may expose painters to particulates that contain carcinogens such as lead chromates and asbestos. The decreased risks of mortality from some neoplasms and circulatory and digestive problems, pneumoconiosis, and "other causes" observed in the painters lack a plausible explanation. Chance or the known limitation of proportionate mortality ratio analysis might play a role. PMID- 9990169 TI - A Model to Estimate the Delivered Doses of Substances in Liquid and Gaseous Phases. AB - A conceptual model is presented for assessing the dose of a chemical substance delivered to individual lung cells when exposure can occur through inhalation of the substance as either a gas or an aerosol of droplets. Assuming a threshold value for the concentration of a toxic species in a single cell, the model shows that the physical state of the substance may affect its biologic activity. Exposure to aerosol droplets of an irritating or reactive substance will deliver much higher surface concentrations to single cells than will a similar exposure to a gas. Under certain conditions, the surface concentration can be between 100 and 10¹0; times higher when the exposure involves an aerosol. Indirect support for the model is found in the observations that threshold limit values for aerosols are generally lower than those for gases. PMID- 9990170 TI - Current Perspectives on Occupational Cancer Risks. AB - On the basis of the International Agency for Research on Cancer's evaluations of occupational exposures, 22 occupational agents are classified as human carcinogens and an additional 22 agents as probable human carcinogens. In addition, evidence of increased risk of cancer was associated with particular industries and occupations, although no specific agents could be identified as etiologic factors. The main problem in the construction and interpretation of such lists is the lack of detailed qualitative and quantitative knowledge about exposures to known or suspected carcinogens. The recent examples of recognized occupational carcinogens, such as cadmium, beryllium, and ethylene oxide, stress the importance of the refinement in the methods for exposure assessment and for statistical analysis on the one hand and the potential benefits from the application of biomarkers of exposure and early effect on the other hand. Other trends that may be identified include the increasing practice of multicentric studies and investigations of exposures relevant to white collar workers and women. Finally, there is a need for investigation of occupational cancer risks in developing countries. PMID- 9990171 TI - The Use of Back Belts to Increase Intraabdominal Pressure as a Means of Preventing Low Back Injuries: A Survey of the Literature. AB - Published reports of relevant empirical research do not suggest a consistent relationship between intraabdominal pressure and the activity of the erector spinae muscles or the magnitude of the intradiscal pressure during lifting. Intraabdominal pressure varies in response to load magnitude and lift method, but there is no pattern of activity that would suggest that an increase in intraabdominal pressure decreases intradiscal pressure. Early models of back biomechanics predicted that the increase in intraabdominal pressure relieved the compressive forces on the low back by providing an extensor moment. In the newer models, intraabdominal pressure functions to stabilize the loaded spine. Studies of human subjects fail to consistently show any clear biomechanical advantage from using a back belt. Some studies suggest a slight decrease in back injury incidence when using a back belt; however, there are conflicting results regarding the severity of the injuries involved and the cost-effectiveness of back belts. PMID- 9990172 TI - The International Dimensions of Lead Exposure. AB - Lead poisoning is among the most prevalent and serious preventable diseases of occupational and environmental origin. Many sources contribute to human exposures, and the residues from past uses continue to present risks due to contamination of dusts, soils, and drinking water. In many aspects, lead poisoning is a local-scale problem, and factors in specific environments and workplaces, as well as characteristics of specific populations, determine the nature and extent of disease. However, lead is also a global pollutant: emissions from stationary and mobile sources are transported across boundaries and even oceans; lead-containing products are traded extensively; and lead-containing wastes such as batteries also move internationally. For these reasons, national regulations are insufficient to prevent this disease. This paper discusses evidence for undertaking international efforts to control lead exposures. PMID- 9990173 TI - Occupational Health in Lebanon: Overview and Challenges. AB - This paper discusses the challenges facing the field of occupational health in Lebanon following 15 years of war. It examines the opportunities for advancing this field and for bringing Lebanese standards up to par with international ones. Challenges include the minor contribution of industry to the overall economy, its perception as nonhazardous, the lack of standards and enforcement, the scarcity of data, and the obscurity of occupational health on the national agenda. Opportunities, on the other hand, have arisen from the need to rebuild the infrastructure and revive tourism, public awareness of the potential hazards of industries in densely populated areas, international pressure, and the return of professionals in occupational health. The safety and salubriousness of workplaces are perceived as minor concerns in Lebanon, yet desire for economic recovery may prove to be an incentive for increased action on this issue. Three potential approaches for action are presented. PMID- 9990174 TI - [Economic aspects of osteoporosis]. AB - BACKGROUND: The objective of this study was to evaluate expenditures and efficacy of osteoporosis treatment in the Czech Republic (CZ) (1.38 million women and 0.99 million men > 55 years of age). METHODS AND RESULTS: Demographic data, incidence of hip fractures and prevalence of osteoporosis and osteopenia in Czech women and men, cost burden to healthcare agencies due to hip fractures and costs of diagnostic procedures, preventive measures and therapies of osteoporosis were obtained from published data and from database of the main health insurance agency (VZP) and the State Institute for Drug Control. The direct costs for treatment of hip fractures in the CZ in 1997 averaged Kc (Czech Crown) 2.5 billion, diagnosis of osteoporosis, Kc 150 million, prevention of osteoporosis using hormone replacement therapy, Kc 66 million, and treatments of osteoporosis which has been applied to less than 5% of osteoporosis patients, 482 million. However, despite the continuously increasing expenditures for treatments of osteoporosis, the incidence of hip fractures doubled in the last 10 years. This is mainly due to increased life expectancy in Czech women and men. CONCLUSIONS: The results of this first economic evaluation of diagnosis, treatment and consequences of osteoporosis in the CZ indicate a need for conceptual decisions in both treatment and prevention of osteoporosis. PMID- 9990175 TI - [Relation of the thickness of the intima and media of the common carotid artery, atherosclerotic plaque in the carotids and manifestations of atherosclerosis in the vessels of the lower extremity in comparison to coronary atherosclerosis]. AB - BACKGROUND: Concomitant occurrence of carotid atherosclerosis, coronary artery disease (CAD) and peripheral vascular disease (PVD) has been described in a number of studies. The objective of the present trial was to assess the degree of correlation between atherosclerosis of the carotid beds as well as PVD and the extent of CAD. METHODS AND RESULTS: Carotid morphologies of 170 patients in total (121 men, 49 women), ranging between 23 and 81 years in age were assessed ultrasonographically. Their carotid beds searched for plaques, stenoses and occlusions. In all patients intima-media thickness (IMT) of the common carotid artery (CCA) were measured ultrasonographically. In addition, case histories of PVD were taken. CAD was proved angiographically in 138 patients. Plaques in carotid beds were found in 98 patients, carotid artery stenoses > 75% were found in 4 patients whereas complete carotid occlusion was not detected in any patient. Clinically manifested PVD was found in 20 patients. A significant difference in IMT of the CCA was assessed by t-test between patients having and not having CAD (0.67 +/- 0.16 mm vs. 0.87 +/- 0.24 mm; P < 0.0001). The correlation between the IMT of the CCA and extent of CAD was weak (r = 0.30, p < 0.01). A positive correlation between carotid plaque occurrence and the number of CAD-affected arteries was statistically assessed (Trend test: P = 0.0001). The sensitivity of incidence of plaques on the carotid beds for prediction of CAD was 64%, the specificity 72%, the positive predictive value 91% and the negative predictive value 32%. The sensitivity of clinically manifested PVD for prediction of CAD was 15%, the specificity 100%, the positive predictive value 100% and the negative predictive value 21%. CONCLUSIONS: The authors confirmed a statistically significant but weak correlation between IMT of the CCA and severity of CAD. They found a positive trend between the occurrence of carotid plaques and the number of CAD-affected arteries. The presence of carotid plaques and clinically manifested PVD were confirmed as a reliable positive predictive factors for CAD. PMID- 9990176 TI - [Light chain deposition disease as a cause of renal failure]. AB - The objective of the paper is to draw attention to a rare cause of rapidly progressing renal failure which developed in the course of four months as a result of light chain deposition disease. The authors submit two case-histories of the disease assessed by renal biopsy after previous clinical and laboratory suspicion of monoclonal gammapathy. In one patient in the sternal punctate plasmacytoma was diagnosed and in the second case it was not possible to detect any type of monoclonal gammapathy or another possible cause of disease. Renal failure was in both cases irreversible and both patients were enlisted in regular haemodialyzation treatment. PMID- 9990177 TI - [Problems with maintenance therapy in opiate dependence and the clinical importance of methadone]. AB - The author presents a review of experience with substitution treatment in opiate dependence. Methadone treatment is most frequently used. An individual daily dose and long-term substitution are desirable for stabilization and motivation of patients included in the methadone programme. Interaction of methadone with some drugs affects the methadone metabolism and calls for a change of the methadone dose and must not be omitted. In addition to methadone there are also other types of pharmacotherapy of opiate dependence (acetylmethadol, buprenorphine). In the Czech Republic in 1997 in the General Faculty Hospital Prague the methadone programme was started. The importance of methadone substitution treatment is beyond doubt and involves improvement of the psychosocial and health status of addicts, gives an opportunity of resocialization and reintegration into society. PMID- 9990178 TI - Should pharmacists sell sterile syringes to injection drug users? PMID- 9990179 TI - The new age of herbals: a pharmacognosy renaissance. PMID- 9990180 TI - A call for self-regulation. PMID- 9990181 TI - Cumulative disadvantage: assessing the attitudes of women and minorities in pharmacy. PMID- 9990182 TI - Pharmacy access to sterile syringes for injection drug users: attitudes of participants in a syringe exchange program. AB - OBJECTIVE: To examine attitudes of participants of a van-based syringe exchange program (SEP) toward the hypothetical prospect of pharmacy-based syringe access. DESIGN: One-time, cross-sectional survey. SETTING: Baltimore, Maryland. PARTICIPANTS: 206 injection drug users who participate in the Baltimore SEP. INTERVENTIONS: Face-to-face interviews. MAIN OUTCOME MEASURES: Location preferred for obtaining syringes, drug and syringe use, past experience with pharmacies, and willingness to pay. RESULTS: The sample was 67% men, 95% African American, and 95% unemployed; mean age was 39.8 years. A total of 19% of respondents had bought syringes at a pharmacy during the prior six months. Some 37% reported having been turned down when asking for syringes at a pharmacy, most commonly due to lack of identification to prove diabetic status (50%). If legal restrictions were lifted, 92% of respondents would obtain syringes from pharmacies, and would be willing to pay a mean price of $0.80 (median = $1.00) per syringe. Women were more likely than men to report the intention to switch from van-based SEP to pharmacy (57% versus 38%, p = .045). CONCLUSION: If current legal restrictions were lifted, pharmacies would be a viable syringe source appealing particularly to women, suggesting gender-specific access issues that should be addressed. The per-syringe price that study participants would be willing to pay exceeds typical retail prices, suggesting that pharmacists could charge enough per syringe to recoup operational costs. PMID- 9990183 TI - Attitudes and practices of pharmacy managers regarding needle sales to injection drug users. AB - OBJECTIVE: To determine Louisiana pharmacy managers' attitudes and practices regarding needle and syringe sales to suspected injection drug users (IDUs) without prescriptions, and to assess which factors affect their decisions to sell nonprescription needles and syringes. DESIGN: Cross-sectional mail survey. SETTING: The six most populous cities of Louisiana. PARTICIPANTS: Pharmacy managers with active permits not affiliated with large hospitals or institutions. MAIN OUTCOME MEASURES: Selling nonprescription needles to suspected IDUs, willingness to sell nonprescription needles to suspected IDUs, and reasons for not selling nonprescription needles to suspected IDUs. RESULTS: Approximately one fourth of the respondents reported that they had sold needles and syringes to suspected IDUs without a prescription. The most frequently cited reason for not selling was fear of increasing drug use; however, many of these pharmacists reported that they would conduct a sale if the customer had a referral from an agency or clinic. CONCLUSION: Pharmacists can assist in the prevention of HIV transmission through nonprescription needle sales to IDUs. This role can be promoted through education of pharmacists and development of referral systems for IDUs. PMID- 9990184 TI - Comparison of melatonin products against USP's nutritional supplements standards and other criteria. AB - OBJECTIVE: To evaluate and compare the quality of a sample of melatonin products, as measured by the United States Pharmacopeial Convention (USP) General Tests and Assays for Nutritional Supplements (other than Microbial Limits) and certain other tests. DESIGN: Five immediate-release, two sublingual, and two controlled release products were randomly gathered from a health food store, groceries, and pharmacies in the Baltimore-Washington metropolitan area. MAIN OUTCOME MEASURES: Weight variation, disintegration (not applicable for controlled-release products), and drug dissolution, based on USP standards. Twelve-hour dissolution profiles were obtained from the controlled-release products. All tablets were also evaluated for friability following the USP procedure and for hardness following unofficial procedures. RESULTS: All products passed the weight variation test. Two products showed excessive friability. Three immediate-release products failed both the disintegration and the dissolution tests. One of the three products demonstrated a threefold difference in hardness. One controlled release product released 90% of melatonin in four hours in the dissolution test; the other released 90% of its content in 12 hours. CONCLUSION: Some products showed evidence of poor formulation and/or poor quality control as indicated by excessive friability, failure to disintegrate and dissolve, and excessive variation in hardness. In vitro release profiles of the two controlled-release products were substantially different. The poor quality of some supplements should be a concern to consumers and health care providers. PMID- 9990185 TI - First-job preferences and expectations of pharmacy students: intergender and interethnic comparisons. AB - OBJECTIVES: To identify and measure intergender and interethnic differences in preferences and expectations of pharmacy students. DESIGN: Two-part survey. One part addressed systematic variations in work-related expectations and preferences between the sexes and among ethnic minorities that may result from cumulative disadvantage or attitudinal traits; the other part focused on similarities and differences in expected sources of job satisfaction and dissatisfaction. SETTING: College of Pharmacy, Nova Southeastern University. PARTICIPANTS: 171 students enrolled in their final semester of didactic training (that is, immediately before rotations or internship). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Significance of intergender and interethnic disparities was determined using t tests. RESULTS: No significant intergender disparities were detected in income expectations, anticipated level of job satisfaction, estimated time from graduation to passing the Board exam or working, or in preferred or expected sector of first job. African American students expected to earn lower levels of income, experience less satisfaction in their first job as a pharmacist, and work longer hours. Hispanic and Asian American students exhibited less confidence in their ability to pass the Board exam and in the allocative function of the job market. Salary and ability to help patients were the two sources of job satisfaction anticipated most frequently, whereas work overload ranked first among the anticipated sources of job dissatisfaction. CONCLUSION: The rapidly changing gender composition of the profession has altered traditional integender differences in outlook and attitudinal traits, contributing to the disappearance of intergender disparities identified in previous research. However, significant interethnic differences in preferences and expectations suggest the presence of cumulative disadvantage among minorities. PMID- 9990186 TI - Opportunities for pharmacists as managers: perceptions of senior executives in the pharmaceutical industry. AB - OBJECTIVE: To determine how senior-level executives in the pharmaceutical industry perceive pharmacists as managers in their industry. DESIGN: Mailed survey. Senior executive officers of 72 companies who were members of the Pharmaceutical Research and Manufacturers' Association indicated in which of 47 different areas an entry-level pharmacy degree would be beneficial for management positions. RESULTS: 40 responses (56%) were received after a follow-up mailing. The areas chosen most frequently were product development and quality control in pharmaceutics (88%), formulation (88%), drug information (88%), quality assurance (85%), pharmaceutics in research (83%), and product management (83%). The 25% of respondents who had a pharmacy background chose more areas where a pharmacy degree would be beneficial (t = 6.87, df = 38, p < .05) than did nonpharmacists. CONCLUSION: To the extent that senior executives represent the current culture and the future direction of the pharmaceutical industry, pharmacists have a variety of career opportunities within pharmaceutical companies. PMID- 9990187 TI - Inter- and intrarater reliability of retrospective drug utilization reviewers. AB - OBJECTIVE: To assess inter- and intrarater reliability among 23 pharmacist and physician retrospective drug utilization reviewers and to assess interrater reliability after a reviewer training session. DESIGN: Exploratory study. SETTING: Maryland Medicaid's retrospective drug utilization review (DUR) program. PARTICIPANTS: 23 physician and pharmacist retrospective drug utilization reviewers. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Profiles rated as "intervention indicated" or "intervention not indicated." Cochran's Q test, overall percent agreement, and the unweighted kappa statistic were used in the analysis of review consistency. RESULTS: Intrarater reliability showed substantial consistency among the 23 reviewers; the percent agreement was 82.9% with kappa = 0.66. Interrater reliability, however, was poor, with an overall agreement of 69.6% and kappa = 0.16. Interrater reliability was also poor after a one-hour reviewer training session (agreement 81.8%, kappa = -0.19). CONCLUSION: The implicit review process used in the retrospective DUR program that we evaluated was unreliable. Since reliability is a necessary but not sufficient condition for validity of an indicator of inappropriate drug use, the validity of the DUR implicit review process is in question. PMID- 9990188 TI - Billing third party payers for pharmaceutical care services. AB - OBJECTIVE: To describe the steps pharmacists must complete when seeking compensation from third party payers for pharmaceutical care services. DATA SOURCES: Government publications; professional publications, including manuals and newsletters; authors' personal experience. DATA SYNTHESIS: Pharmacists in increasing numbers are meeting with success in getting reimbursed by third party payers for patient care activities. However, many pharmacists remain reluctant to seek compensation because they do not understand the steps involved. Preparatory steps include obtaining a provider/supplier number, procuring appropriate claim forms, developing data collection and documentation systems, establishing professional fees, creating a marketing plan, and developing an accounting system. To bill for specific patient care services, pharmacists need to collect the patient's insurance information, obtain a statement of medical necessity from the patient's physician, complete the appropriate claim form accurately, and submit the claim with supporting documentation to the insurer. Although many claims from pharmacists are rejected initially, pharmacists who work with third party payers to understand the reasons for denial of payment often receive compensation when claims are resubmitted. CONCLUSION: Pharmacists who follow these guidelines for billing third party payers for pharmaceutical care services should notice an increase in the number of paid claims. PMID- 9990189 TI - Infertility update: use of assisted reproductive technology. AB - OBJECTIVE: To describe assisted reproductive technology (ART) and use of medications during these procedures. DATA SOURCES: Recent clinical literature. STUDY SELECTION: Not applicable. DATA EXTRACTION: Not applicable. DATA SYNTHESIS: ARTs are procedures used in treatment of infertility that involve removal of oocytes and their manipulation outside the woman's uterus. The simplest form of ART, in vitro fertilization, involves aspirating eggs from the ovaries, fertilizing them outside the body, and transferring the embryos into the uterus at the four- to eight-cell stage. Experimental regimens for in vitro fertilization include use of various medications (gonadotropin-releasing hormone agonists, human menotropins, follicle-stimulating hormone, growth hormone) at varying points in the menstrual cycle and after introduction of the embryo into the uterus. Human chorionic gonadotropin has been used to increase implantation of embryos during the woman's luteal phase. Gamete intrafallopian transfer (GIFT) involves transfer of oocytes and sperm into the fallopian tubes, where fertilization takes place. This technique has the advantage of causing the zygote to enter the uterus at the time it would during natural conception. Zygote intrafallopian transfer is similar to GIFT, except that fertilization occurs in vitro, with embryos placed in the fallopian tubes at the two-cell stage. Various micromanipulation techniques and innovative sperm aspiration procedures are currently under development. CONCLUSION: Many advancements have been made in ART, and pharmacists who understand these procedures can serve patients by providing medication information in an empathetic and supportive manner. PMID- 9990190 TI - Analysis of grocery chain pharmacists' work-related behaviors. AB - OBJECTIVE: To measure grocery chain pharmacists' work-related behaviors to assess the impact of a Pharmaceutical Care Certificate Program (PCCP) and other future interventions intended to alter pharmacists' practice behaviors. DESIGN: This study used multidimensional work sampling (MWS), a work measurement methodology that breaks "work" into three components: activity (what was done), contact (with whom the activity was performed), and function (the purpose or objective of the activity). Pharmacists were signaled at random intervals during the workday by a random signal generator. A selection was made from a list of items in each of the three dimensions of work to form an activity-contact-function combination code that described the work-related behavior at that point in time. SETTING AND PARTICIPANTS: Pharmacists in 15 grocery chain stores in the Indianapolis area; 20 pharmacists were enrolled in Purdue University's PCCP and 10 served as controls. Data were collected for a period of six weeks during April through June 1997 before the beginning of the PCCP program. MAIN OUTCOME MEASURES: Pharmacists' work-related behaviors. RESULTS: Writing/keyboarding was the most frequently recorded activity (22%), followed by one-to-one meetings (21.6%), and drug preparation (18%). Pharmacists spent most of their time working alone (62.9%), while a smaller but still substantial proportion of time was spent interacting with patients (17.9%). The most frequently recorded purpose (i.e., function) of pharmacists' activities was drug distribution (23.9%), followed by personal time (12.4%), receiving or transferring a medication order (10.2%), and patient counseling (6.6%). Out of a possible, 1,760 activity-contact-function combinations, 10 accounted for 46.3% of all reported observations, with "Prepare drug-Self-Drug distribution" representing the most frequently recorded activity contact-function combination (15.7%). CONCLUSION: MWS is useful in helping grocery chain management better understand how pharmacy personnel are currently being utilized. This study provides a baseline for evaluating the impact of training programs or other alterations in the practice environment on pharmacists' work-related behaviors. PMID- 9990191 TI - Elements of a pharmaceutical care plan. PMID- 9990192 TI - Fomiversen sodium approved to treat CMV retinitis. PMID- 9990193 TI - Lyme disease: geography predicts risk. PMID- 9990194 TI - MEDLINE and the new health care consumer. PMID- 9990195 TI - Dynamic morphology of erythrocytes revealed by cryofixation technique. AB - This article summarizes our research on the morphology of dynamically changed erythrocyte shapes, as revealed by electron microscopy with cryofixation techniques. Cryofixation is a better way to immobilize functioning morphology in cells and tissues than conventional fixation methods because of faster freezing time. Our cryofixation techniques were used to detect erythrocyte shapes in flow and ultrastructural changes of membrane skeletal components. This required that we develop some new preparation techniques which we called, erythrocyte-splitting method, in vivo cryotechnique or in vitro cryotechnique for erythrocytes. By using various combinations of these cryofixation techniques with freeze fracturing, freeze-substitution or deep-etching method, the native morphology of erythrocytes under various physiological or pathological conditions could be assessed by scanning or transmission electron microscopy. PMID- 9990196 TI - [Transcytosis of immunoglobulin IgG]. AB - Recent studies on cellular mechanism of transmission of maternal IgG are briefly reviewed. The mechanism has been studied in rodent intestine and yolk sac, where the role of neonate Fc receptors (FcRn) in the transcellular transport of IgG is now well understood. FcRn binds IgG on the cell surface (intestine) or in endosomes (yolk sac) at around pH 6.0. The IgG-FcRn complex is sorted into vesicles from the apical endosome, and transported basolaterally to release IgG extracellularly. In the human placenta, Fc gamma RIII and MHCI-related human Fc receptors (hFcRn) are expressed in the syncytiotrophoblast and are involved in the specific binding and transcytosis of IgG. Small GTP-binding proteins rab4 and/or rab5A are immunohistochemically localized on recycling and/or sorting endosomes, suggesting their involvement in forming vesicles transporting the IgG FcR complex. Several other GTP-binding proteins and SNAREs are assumed to regulate this process, but remain to be identified. The cellular mechanism of IgG transcytosis, including endocytosis, sorting, fusion and exocytosis may be elucidated in terms of regulator proteins in near future. PMID- 9990197 TI - [Morphological transformation of sensory ganglion neurons and satellite cells]. AB - Sensory ganglion neurons in higher vertebrates are unique in that they are pseudounipolar with a single stem process that divides at some distance from the cell body into central and peripheral processes. In the early stages of development, these neurons are bipolar but later they became pseudounipolar. This developmental process of sensory ganglion neurons with satellite cells was examined by scanning electron microscopy following removal of connective tissue. This pseudo-unipolarization began earlier but proceeded at a slower rate in chick than in rat embryos. This difference may due to the difference found in the extent and intimacy of satellite cell investments in these two animals, which was due to the fact that sensory neurons undergo pseudo-unipolarization only in the presence of satellite cells in vitro. The neuronal perikaryal projections were observed by scanning electron microscopy after removal of connective tissue and satellite cells. Morphometric analysis reveal that perikaryal projections were more numerous on the surface of mature pseudounipolar neurons than on the surface of premature bipolar neurons, and that the number of projections increased as the neuronal cell bodies grew larger. This may support the hypothesis that perikaryal projections are structural devices for increasing the neuron-satellite interface and for improving the efficiency of metabolic exchange between these two cell types. These results suggest that satellite cells play an important role in neuronal maturation. PMID- 9990198 TI - [Clinical anatomy of blood vessels supplying the central nervous system]. PMID- 9990199 TI - The femoral sulcus angle in neonatal cadavers: a macroscopical and ultrasonographical study. AB - The shape of the femoral sulcus is an important factor in patellofemoral congruence. The aim of the present study was to investigate the femoral sulcus angle using neonatal cadavers through ultrasonographic and macroscopic observations, in order to evaluate the differences between those two methods and also in order to compare them with adult data published previously. Both knees of 20 neonatal cadavers were examined to measure the femoral sulcus angle. The mean cartilaginous femoral sulcus angle was 145.77 degrees on the macroscopic measurements, and 146 degrees in the ultrasonographic examinations. There was no significant difference between neonatal and adult values and between ultrasonographic and macroscopic measurements (P > 0.05). In the most of the knees two condyles were symmetrical (92.5%). In conclusion the cartilaginous femoral sulcus angle is completely formed in the neonatal age group. Internal and external factors during childhood may be responsible for condylar dysplasia. PMID- 9990200 TI - Bifid ribs observed in the third and the fourth ribs. AB - Three cases of bifid ribs were found in two cadavers during routine dissections at the Iwate Medical University School of Dentistry. All of the cases were found in the third or the fourth rib. The distal parts of the osseous rib bifurcated with an angle of 60 degrees and both of the branches had their own costal cartilage. The costal cartilage fused again to form the trunk which was connected to the sternum. The space between the two branches was filled with presumably normal intercostal muscles. Blood supply was maintained by a small branch from the interthoracic artery to the upper branches. However, the intercostal nerves did not branch toward the upper branch but only ran along the lower margins of the lower branches of the bifid ribs. PMID- 9990201 TI - Accessory insertions of pectoralis major muscle to the brachial fascia: a case report. AB - Two accessory fibrous bands arising from the posterior aspect near the lateral border of the pectoralis major muscle were found to attach to the brachial fascia at the posterior arm region. Those bands were in intimate contact with the median nerve, brachial veins and its branches. They were thought to be remnants of the distal origin of the pectoralis major muscle. The impact of those fascial bands in the compression syndromes of the upper extremity and in the surgical operations directed to the fossa axillaris were discussed. PMID- 9990202 TI - [Dorsoventral limb patterning based on anatomical analysis of muscles and nerve plexuses]. AB - The developing vertebrate limb is an excellent system to study the mechanisms that lead to skeletal, muscular and nervous patterns. Pattern formation in the limb occurs in relation to three axes: the antero-posterior axis, the proximo distal axis and the dorso-ventral axis. Extensive classical embryological experiments on chick limb buds have identified some of the cell interactions related to these three axes. Recent works in developmental biology have begun to identify the molecular basis of these cell interactions which control patterns and forms of the limb. In this review, a possible model of dorsoventral limb patterning is proposed, based on an experiment using ectoderm/mesoderm recombinations in which the dorsoventral axis of the tissues is inverted. Based on comparative anatomical studies of the shoulder and pelvic regions, the anatomy of the transitional zone between limb and trunk regions is discussed. In addition, the problem of the nerve-muscle relationship in gross anatomy is also discussed from the viewpoint of the pattern formation. PMID- 9990203 TI - [Signaling molecules involved in induction and early patterning of limb buds]. AB - Soluble signaling factors are involved in morphogenetic events during vertebrate limb development. They belong to the Hedgehog family, the bone morphogenetic protein (BMP) family, the fibroblast growth factor (FGF) family and the Wnt family. FGF-8 and FGF-10 play central roles to specify the limb field and promote initial outgrowth. In the established limb bud, FGF-4, FGF-8 and BMP-2 are secreted in the apical ectodermal ridge and control proximal-distal pattern formation. In the zone of polarizing activity Sonic hedgehog is produced and pattern along the anterior-posterior axis. Members of the BMP family may be the secondary signals in this patterning. Wnt-7a from the dorsal ectoderm dorsalizes limb mesenchyme and controls dorsal-ventral patterning. These factors expressed in the signaling centers in limb buds influence gene expression each other and coordinate limb morphogenesis. PMID- 9990204 TI - [Molecular mechanism of limb muscle patterning]. AB - Pattern formation of the limb muscles involves a network between intrinsic programs of gene expression in myogenic precursor cells and extrinsic signals derived from the surrounding tissue. The cells at the lateral edge of the somite are specified to the precursors of the hypaxial muscles by intercelluler interaction with the dorsal ectoderm and the lateral mesoderm. At the level of the limb bud, these premyogenic cells expressing c-MET and Pax-3 are induced to invade into the limb bud by HGF/SF and unknown chemotactic signal(s) exerted by the limb mesenchyme. It is likely that N-cadherin and some extracellular matrixes are involved in this phenomena. In the limb bud, myogenic cells proliferate under influence of the limb ectoderm and congregate into the premuscle masses. BMPs expressed in limb ectoderm may maintain the proliferative phase of the myogenic cells by inhibition of the myogenic differentiation. Recently, detailed analysis of expression of Hox genes in the chick limb musculature suggests that Hoxa-11 and Hoxa-13 autonomously regulate the pattern formation of the limb muscles. Hoxa 11 is induced in the myogenic cells by an interaction with the limb mesenchyme as soon as they invade into the limb. It is possible that Hoxa-11 may confer a limb specific property on these myogenic cells. After the formations of muscle masses, Hoxa-11 and Hoxa-13 are expressed in the muscle masses in region-specific manner along the anteroposterior and proximodistal axes under the control of the limb mesenchyme and the polarizing signal(s). They are candidates for intrinsic regulator of myogenic cells that control 1) the splitting processes of the muscle masses and 2) the specification of each muscle. PMID- 9990205 TI - [Cell-to-cell recognition in limb pattern formation]. AB - Vertebrate limb is used as a model system to understand the mechanism of pattern formation in development. Mesenchymal cells of the limb bud are differentiated into chondrogenic cells or fibroblastic cells. The chondrogenic cells form bifurcated and segmented cartilage structure. This cartilage pattern is regulated by many signaling molecules and transcriptional factors. In the early stage of cartilage differentiation, mesenchymal cells aggregate into suitable region in the limb bud, and the aggregates form prepattern of skeletal elements. Cell adhesion molecules have been shown of their involvement in this cell aggregate formation and the cartilage differentiation process. Expression of these cell adhesion molecules and other cell surface molecules may be regulated by signaling molecules or transcriptional factors, although no regional specificities of these molecules have been reported. In this review, we describe about regional differences of cell affinity of limb bud mesenchyme. We show the differential cell affinity represents the positional identity of the mesenchyme in limb bud, and glycosylphosphatidylinositol (GPI) anchored cell surface proteins are involved in this different cell affinity. From these results, we discuss the importance of the cell affinity in pattern formation of limb bud. PMID- 9990206 TI - [Genetics of the limb pattern formation in mouse]. AB - Genetics studies using mouse mutants have revealed key functions of several genes in limb development. In this review, I summarized approaches of forward genetics to elucidate genetic control of mouse limb development based on mouse limb mutants. In mouse, there are many mutants that exhibit malformation in distal elements (autopod) of limb, i.e. polydactyly and ectrodactyly. Some of them are reported as failure in the generation and maintenance of axes in limb development. Recent advance in genome analysis has allowed us to identify and clone the causative gene of mouse mutants by positional cloning technique. In addition, analysis of expression patterns of marker genes that play key roles in limb development gives some hints with respect to the functions of the affected genes. In many cases, the same mutants show different manifestations of the phenotype on different genetic backgrounds, indicating the presence of the second gene that may genetically interact with the original mutant gene. This also affords very useful opportunity to study epistatic interaction of genes involved in the relevant phenotypes. Thus, all these approaches of forward genetics facilitate to understand the genetic control of limb development of mouse. PMID- 9990207 TI - [Dorso-ventral patterning of the vertebrate limb and dermatoglyphs with special reference to the pad pattern of mice]. AB - The proximo-distal (P-D), antero-posterior (A-P) and dorso-ventral (D-V) axes are important for normal limb development in vertebrates. It has been reported that D V axis is decided by Wnt-7a, Lmx-1 and Engrailed-1 (En-1) which are expressed in the limb bud along D-V axis. These factors are thought to be required for formation of the apical ectodermal ridge (AER) which is necessary for outgrowth of the limb. The results from spontaneous mutant mice meromelia (mem), which exhibits double-dorsality of the distal limb, suggested that other factors, not only En-1 and Wnt-7a are required for decision of AER, and mem was probed to be novel gene regulating En-1 and Wnt-7a directly or indirectly. The dorsalized ventral structures in meromelia were found by observation of the pad pattern. Pad pattern is always constant in normal mice, and each pad indicates particular part of the limb. So pad pattern is useful to detect and describe anomalies even in the limbs without skeletal defects. The process of pad development is associated with the limb patterning, and abnormal pad pattern may indicate pathogenesis of abnormal limb development. The mouse pad pattern is usable as the model for human dermatoglyphs, and it is also important to investigate mechanisms of human diseases. PMID- 9990208 TI - [Effects of hypertonic lactated Ringer's solution on hepatic ATP and L/P ratio in rats subjected to acute hemorrhage]. AB - This study aimed to clarify the difference in the effects of hypertonic lactated Ringer's solution (HLS) on hepatic ATP level and L/P ratio during acute hemorrhage in rats. The hepatic ATP level in HLS 230 group was lower, and L/P ratio in HLS 300 group was higher than those in the control group. There was no significant difference in glycogen among 4 groups. However, pH and the base excess in HLS 230 and HLS 300 group were significantly higher than those in the C group. Heart rate in HLS 300 group was significantly lower than that in the C group. These results suggest that HLS may not be useful with regard to the hepatic energy metabolism, although it improves the metabolic acidosis during acute hemorrhage. PMID- 9990209 TI - [Lung collapse during one lung ventilation does not change low frequency respiratory mechanics]. AB - The present study was carried out to clarify the effects of lung collapse for one lung ventilation on respiratory system impedance during thoracic surgery. We measured the impedances of respiratory system (RS) in eight paralyzed subjects under anesthesia employing a pseudorandom noise forced volume oscillation technique. These measurements were performed before and after the one lung ventilation. The impedance values were fitted to a mathematical model consisting of a single conduit connected with a viscoelastic parenchyma. Lung collapse did not affect resistance and reactance in RS after the re-expansion. The mathematical modeling showed no significant effect of one lung ventilation on all the parameters of airway and parenchyma. There was no difference in model fit of the parameters, indicated by the presence of the goodness-of-fit parameter (chi 2), before and after lung collapse. In conclusion, lung collapse during one lung ventilation does not change low frequency respiratory mechanics. PMID- 9990210 TI - [Neuromuscular inhibitory effects of propofol evaluated by cat's evoked EMG]. AB - Neuromuscular inhibitory effects of propofol were investigated in 7 cats using muscular compound action potential (mCAP) elicited from the gastrocnemius muscle by sciatic nerve stimulation. A rectangular pulse of supramaximal strength and duration of 0.2 msec was applied serially to the sciatic nerve at 0.1 Hz during the experiments, and mCAPs obtained from the gastrocnemius muscle were recorded. After obtaining a constant mCAP amplitude, a series of 8 consecutive mCAPs (M 1 8) evoked by repetitive stimulation at 100 Hz was recorded, and M 8/M 1 amplitude ratio (M 8 amplitude/M 1 amplitude.100%) was calculated as the control value. After control variables had been obtained, initial dose of 2.5 mg.kg-1 of propofol was administered intravenously followed by continuous infusion with incremental dosages of 10, 20, 50 and 100 mg.kg-1.hr-1 of each 30 minute duration. The effects on mCAPs evoked by single and 8 consecutive repetitive stimulation were observed in each period. The depression of single mCAP amplitudes and fading responses in the M 8/M 1 amplitude ratios were not observed at any infusion rate. Our results suggest that propofol has no influence on neuromuscular transmission in cats when administered intravenously at 10 times of human clinical infusion doses. PMID- 9990211 TI - [Is patient-controlled sedation good for elderly patients?]. AB - The purpose of this study was to evaluate the safety and advantage of intra operative patient-controlled sedation (PCS) in elderly patients. Propofol PCS was compared with anesthesiologist-controlled sedation (ACS) during knee arthroplasty under epidural anesthesia. Eleven elderly patients scheduled for unilateral knee total or partial arthroplasty were divided randomly into PCS group (n = 6) and ACS group (n = 5). Epidural anesthesia was performed to produce an appropriate level of sensory block (T 10 through S). Firstly a mixture of pentazocine 0.2 mg.kg-1 and 2% mepivacaine 6-9 ml was injected to the epidural space, and anaesthesia was maintained using 2% mepivacaine afterward. Patients in both groups received propofol 0.3 mg.kg-1 i.v. as a loading dose and 0.6 mg.kg-1.h-1 continuous infusion. Furthermore patients in PCS group received propofol PCS (bolus: 0.2 mg.kg-1, lockout time: 3 min). Patients in ACS group were administered propofol continuously and infusion rates were regulated to maintain a sedation score 3 (Wilson et al) by anesthesiologist. Respiratory rate, blood pressure, heart rate, SpO2, arterial blood gas analysis and plasma levels of propofol were measured 4 times during and after the surgery. Satisfaction of patients and surgeons was questioned. Patients in PCS group received a mean propofol dose of 1.9 +/- 0.1 mg.kg-1 during procedures with a mean duration of 147 min. On the other hand patients in ACS group received propofol 2.9 +/- 0.3 mg.kg-1 with 142 min of procedures. Satisfaction of patients and surgeons, the incidence of complication were similar between the groups. For elderly patients who undergo epidural anesthesia, PCS is a safe and effective technique providing similar good sedation as with ACS. PMID- 9990212 TI - [Spread of spinal anesthesia with 3 different hyperbaric solutions used in Japan]. AB - We studied the spread of spinal anesthesia with 3 different hyperbaric solutions commercially available in Japan. Percamin-S [0.3% dibucaine in 5% hyperbaric saline] (P), Neo-Percamin.S [0.24% dibucaine with 0.12% T-caine in 9.5% glucose] (N) and 0.5% Tetcaine [tetracaine] in 10% glucose (T) were studied. Two ml of each solution was administered intrathecally using a 25 gauge Quincke needle. Patients (n = 90) were allocated to one of 9 groups receiving 2 ml of P, N or T at L 2-3, L 3-4 or L 4-5 interspace. Both N and T produced significantly higher spread of analgesia than P at any of L 3-4 and L 4-5 interspaces. P and N have the same specific gravity, even though significant differences were found in spread of segmental analgesia. Local anesthesic agents and solvent solutions themselves are considered to influence the spread of spinal anesthesia as the specific gravity of hyperbaric solution does. PMID- 9990213 TI - [Bispectral index based comparison of propofol dose requirement combined with various types of analgesic methods for total intravenous anesthesia]. AB - We hypothesized that propofol dose requirement for total intravenous anesthesia is varied with the analgesic methods during anesthesia if the depth of anesthesia is maintained at the same level with bispectral index. Adult gynecological patients without any complications were randomly allocated to four groups; propofol with 1) continuous epidural block-oxygen-nitrous oxide (n = 18), 2) continuous epidural block-oxygen-air (n = 21), 3) fentanyl (total 5 micrograms.kg 1)-oxygen-nitrous oxide (n = 18) and 4) fentanyl (total 5 micrograms.kg-1)-oxygen air (n = 21) group. Propofol 1.5 mg.kg-1 and vecuronium 0.15 mg.kg-1 were administered intravenously for endotracheal intubation. Propofol was titrated to maintain bispectral index between 40 and 60. Total dose of propofol except the dose for induction was compared among the groups with one-way ANOVA and Scheffe's F test and P < 0.05 was considered as significant. Results were expressed as means +/- SDs. The age, body weight, height and hemodynamic changes during anesthesia among the groups were not significantly different. Total required dose of propofol for continuous epidural block-oxygen-nitrous oxide, continuous epidural block-oxygen-air, fantanyl-oxygen-nitrous oxide and fentanyl-oxygen-air group were 4.78 +/- 0.87 mg.kg-1.h-1, 6.10 +/- 0.93 mg.kg-1.h-1, 5.79 +/- 0.75 mg.kg-1.h-1 and 6.58 +/- 1.19 mg.kg-1.h-1, respectively. Nitrous oxide was able to reduce the dose of propofol significantly either with epidural anesthesia or fentanyl used for analgesia. PMID- 9990214 TI - [Transdermal nitroglycerin before induction of anesthesia prevents redistribution hypothermia in patients under general anesthesia]. AB - Initial anesthesic-induced hypothermia results largely from core-to-peripheral redistribution of heat. Administration of transdermal nitroglycerin induces vasodilation. Such vasodilation, induced well before induction of anesthesia, might redistribute heat to peripheral tissues. Minimal redistribution hypothermia might accompany subsequent induction of anesthesia. We studied 32 patients undergoing gastrointestinal surgery. Thirty minutes before induction of anesthesia, they were randomly assigned to: 1. transdermal nitroglycerin 10 mg; 2. transdermal nitroglycerin 5 mg; and, 3. control. Core temperature during the first hour of anesthesia decreased significantly more in the control patients than in those given either dose of nitroglycerin. Vasodilation induced by transdermal nitroglycerin before induction of anesthesia significantly decreased subsequent redistribution hypothermia. Drug-induced modulation of vascular tone thus produces clinically important alterations in intraoperative core temperature. PMID- 9990215 TI - [Prevention of contamination with a heat-and-moisture-exchanger (HME) and bacterial filter during clinical anesthesia]. AB - Although the use of HME and bacterial filter is a common practice to protect the anesthesia machine as well as the patients from bacterial contaminants, there is no report demonstrating the effectiveness of this filter in clinical anesthesia setting. We evaluated the actual effectiveness of the filter during clinical use. While the anesthesia breathing circuit, two bacterial filters (BB 50 T, Nihon PALL) and anesthesia bag, which were sterilized with ethylen oxide gas (EOG), were connected to the anesthesia machine and used continuously for one week, EOG sterilized HME and bacterial filter (BB 25 A, Nihon PALL) were changed before each anesthesia. Culture samples were taken from the BB 25 A, the breathing circuit and the machine side of the BB 50 T. Of the 117 BB 25 A samples taken, 6 were positive for Micrococcus, alpha-Streptococcus, Bacillus, and Staphylococcus epidermidis. From 21 breathing circuit "internal" samples, one was positive for Bacillus, Staphylococcus epidermidis. But the contamination from outside sources was suspected, since all the BB 25 as used with this circuit were negative. Use of BB 25 A prevents contamination of the breathing circuit for a period of one week. If we use BB 25 A in every anesthesia case, the changing of the breathing circuit is unnecessary, reducing the cost and simplifying procedures during clinical practice. PMID- 9990216 TI - [Current topics in the regulation of prostanoids--2. The interaction with cytokines and nitric oxide]. AB - Cyclooxygenase (COX)-2 is induced by proinflammatory cytokines such as interleukin (IL)-1 beta, cytokines produced from helper T cell subpopulation Th 1, such as interferon-gamma and tumor necrosis factor-beta. Cytokines produced by the T cell such as IL-4, IL-10, and IL-13 down-regulate induction of COX-2. The novel MAP kinase pathway, JNK and/or p 38, are important intracellular signaling pathways for induction of COX-2. The increased production of prostaglandin E2 by upregulation of COX-2 increases IL-6 production. By utilizing a COX-2 blocker, it is possible to decrease IL-6 production via reduction of prostanoid production, thereby attenuating the systemic inflammatory response. Nitric oxide (NO) and prostanoids are also known to interact and regulate each other. It is important to note the interactions between prostanoids and cytokines or other inflammatory mediators such as NO in understanding the mechanism of the anti-inflammatory effects of prostanoid regulation. PMID- 9990217 TI - [The effects of low-doses of fentanyl, buprenorphine and pentazocine on circulatory responses to endotracheal intubation]. AB - This study evaluates the effects of low-doses i.v. fentanyl, buprenorphine and pentazocine on circulatory responses of endotracheal intubation in 70 scheduled surgical patients. Patients were allocated to 5 groups randomly and 2 (n = 11) or 4 (n = 13) micrograms.kg-1 of fentanyl, 0.5 mg.kg-1 of pentazocine (n = 13), 5 micrograms.kg-1 of buprenorphine (n = 10) and saline as a control (n = 23) were administered 5 minutes before the administration of thiopental, respectively. Then, patients were intubated with 0.1 mg.kg-1 of vecuronium. Blood pressure and heart rate were recorded. Only 4 micrograms.kg-1 of fentanyl diminished circulatory responses of systolic blood pressure on the stimuli of endotracheal intubation. PMID- 9990218 TI - [Perinatal and perianesthetic management of the sacrococcygeal teratoma in a neonate]. AB - We report perinatal and perianesthetic management of a female infant with sacrococcygeal teratoma who underwent fetal bladder puncture and postnatal tumor resection. At 33 weeks' gestation, fetal ultrasonography revealed an intrapelvic mass, oligohydramnios and the dilatation of the bladder. At 34 weeks' gestation, bladder puncture was performed in utero to relieve urinary obstruction by the mass. And it served to reserve the renal function but caused remarkable ascites at birth due to urine leakage to the peritoneum through the puncture site. After the delivery by cesarean section, the patient underwent the tumor extirpation at 2 days of life. The operation and anesthesia proceeded uneventfully. In previous reports, several mortalities due to exsanguinating hemorrhage during surgery have been reported. In addition, sacrococcygeal teratoma is occasionally accompanied by coagulopathy and high output cardiac failure caused by arteriovenous fistulae. Therefore it is important for good patient outcomes to evaluate preoperatively the risks mentioned above. PMID- 9990219 TI - [Anesthesia for abdominal surgery after percutaneous transluminal coronary angioplasty (PTCA)]. AB - From December 1989 to October 1996, 1,318 PTCAs (percutaneous transluminal coronaly angioplasty) were performed for AMI (acute myocardial infarction) or postinfarction angina in our institute. Within 7 days to 71 days after successful PTCA, five patients who had been diagnosed as cholelithiasis or gastric cancer were operated under general anesthesia. Performed operations were cholecystectomy in the first patient, subtotal gastrectomy in the second, third and fourth patients, and total gastrectomy and cholecystectomy in the fifth patient. There was no serious cardiac complication during the operations and perioperative period. PTCA is considered to have decreased cardiac complications in patients with ischemic heart disease having undergone abdominal surgery. PMID- 9990220 TI - [A case of endotracheal tube obstruction caused by pneumoperitoneum during laparoscopic cholecystectomy]. AB - A 56-year-old man with cholecystolithiasis was scheduled for laparoscopic cholecystectomy. Anesthesia was induced with pentazocine and propofol i.v., and the trachea was intubated using vecuronium i.v. Anesthesia was maintained with 70% nitrous oxide and 1-3% sevoflurane in oxygen, and vecuronium was used for muscle relaxation. The lungs were mechanically ventilated with a tidal volume of 600 ml and a respiratory rate of 8 cycles.min-1. Following induction of carbon dioxide pneumoperitoneum, blood pressure, PETCO2 and peak inspiratory pressure gradually increased. PETCO2 increased from 33 mmHg to 48 mmHg despite increase in the respiratory rate to 20 cycles.min-1. By 45 minutes after the beginning of surgery, PETCO2 had increased to 60 mmHg, and ventilation of the lungs was impossible. Bronchofiberscopy revealed obstruction of the endotracheal tube by tracheal mucosa. The endotracheal tube was then drawn out by 2 cm with slight recovery of ventilation. After 1 h 16 min of surgery, it was observed that the patient had developed pneumoscrotum and subcutaneous emphysema extending from femoral area, abdomen, and thorax to the right neck. Chest rentogenography revealed a slight tracheal shift and subcutaneous emphysema. One hour after the end of surgery, PaCO2 was 48.9 mmHg under spontaneous respiration. We speculate that the pneumoperitoneum shifted the tracheal carina cephalad, causing obstruction of the endotracheal tube. Our findings show that displacement of the endotracheal tube must be carefully monitored during laparoscopic cholecystectomy. PMID- 9990221 TI - [Sevoflurane anesthesia for myotonic dystrophy]. AB - We successfully anesthetized a 14-year-old boy with myotonic dystrophy for orthopedic surgery using sevoflurane. Sevoflurane enabled anesthetic induction and tracheal intubation without intravenous anesthetics and muscle relaxants. Sevoflurane also provided stable anesthetic maintenance without intravenous anesthetics. The patient showed rapid anesthetic recovery and adequate spontaneous breathing. We conclude that sevoflurane is a useful anesthetic for patients with myotonic dystrophy. PMID- 9990222 TI - [Clinical experience at Uppsala University]. AB - The author had a chance to study at the Department of Cardiothoracic Anesthesia at Uppsala University Hospital, Uppsala, Sweden. About 12 hundred cases of open heart surgery and thoracic surgery are done by cardiothoracic anesthesiologists every year. Most of the cardiac anesthesia was performed with low flow anesthesia using mixture of oxygen-air-isoflurane, from economical and environmental view points. Early extubation is common at Uppsala University. The patients were extubated at the intensive care unit on the day of surgery. The author also visited the central surgery suite. More than 12 thousand surgeries per year, including hepatic and renal transplantation, are performed. General intensive care unit, emergency medicine were managed and organized mainly by anesthesiologists. The role of anesthesiologists are well appreciated and they are respected in Sweden. PMID- 9990223 TI - [Microsatellite instability and mismatch repair system]. PMID- 9990224 TI - [The influence of dietary lipids on nephrolithiasis in rats]. AB - PURPOSE: The influence of dietary lipids on nephrolithogenesis is unclear. In the present study, I investigated the role of dietary lipids concerning both the etiology and the prevention of nephrolithiasis using 9-week-old male Wistar rats. METHODS: Study 1: The rats were divided into five groups and reared on standard, low protein, high protein and high cholesterol diets for 23 weeks. Study 2: The effects of cholesterol on nephrolithiasis was examined. The animals were given a 30 intraperitoneal injection of 2 ml of 8.5% calcium gluconate. Study 3: A nephrolithiasis model was prepared by intraperitoneal administration of 40 mg/kg of glyoxylic acid and 0.25 microgram of vitamin D3 daily for 2 weeks. The inhibitory effects of eicosapentaenoic acid (EPA) on nephrolithiasis were studied. RESULTS: Study 1: In the groups given the high protein and high cholesterol diets, an increase in renal osteopontin-mRNA, one of the major matrix ingredients of stones containing calcium, was observed. Study 2: Microlith was more frequently observed in the high cholesterol group than in the standard diet group. Study 3: In the EPA group, lithiasis was less extensively than in the groups administered distilled water or olive oil, and this was assumed to be caused by factors other than inorganic substances such as calcium and oxalic acid in the urine. When the renal tissue specimens in Studies 2 and 3 were examined, initial calcium deposition was found to start from the basement membrane of renal tubular cells and gradually spread throughout the cells. CONCLUSION: These results suggested that cholesterol is a risk factor in nephrolithiasis, and EPA is effective in its prevention. The elimination of hyperlipidemia should be included in dietary instructions for nephrolithiasis patients. PMID- 9990225 TI - [An urodynamic study on neobladder function]. AB - OBJECTIVE: To analyze the urodynamic characteristics of neobladders, we conducted a pressure-flow study in patients with orthotopic urinary reservoirs. PATIENTS AND METHODS: From 1986 to 1996, 90 patients underwent bladder replacement following cystectomy, using a right colonic, ileocolic, ileal, or sigmoid colonic segment. The subjects were 38 patients (31 men and 7 women) with stable urination and no evidence of cancer recurrence, urethral stricture, urinary tract infection or vesicoureteral reflux. Their mean age was 60.5 years, with a range of 38 to 77 years. Information on neobladder function, such as desire to void, force of micturition, urinary incontinence and other complaints, was obtained by questionnaire. A pressure-flow study was performed in all patients 3 months to 103 months postoperatively to evaluate total reservoir pressure, abdominal pressure and subtracted reservoir pressure during filling and voiding phases. RESULTS: Ten of 38 patients (26.3%) were dissatisfied with their neobladder function, due to weakness of urinary sensation, loss of urinary force and enuresis. In 6 of the 7 patients with enuresis, the urinary reservoir had been created by Heineke-Mikulicz's procedure of detubularization; 4 of these patients had a high degree (over 40 cmH2O) of phasic contraction during the filling phase. In only 2 of the 38 patients, a pressure-flow study showed an almost same pattern as that obtained with a normal urinary bladder. Twelve patients had increased electromyogram of the external urethral sphincter during the voiding phase, while half of the 38 patients showed a flat electromyogram during both the filling and voiding phases. Thus, 31 of 38 patients revealed a sphincter dyssynergia pattern. Mean total reservoir pressure at maximum cystometric capacity was 65.5 +/- 42.1, 48.4 +/- 19.0, 66.0 +/- 61.0 and 107.0 +/- 43.3 cmH2O in ileal, ileocecal, right colonic and sigmoid neobladders, respectively. The value for sigmoid neobladder was statistically different from that for ileocecal neobladder (p < 0.05). Mean total reservoir pressure at maximal flow was 73.1 +/- 42.4, 56.4 +/- 22.6, 88.9 +/- 69.4 and 94.0 +/- 31.8 cmH2O in ileal, ileocecal, right colonic and sigmoid neobladders, respectively. There were no statistically significant differences among these values. The ratio of subtracted reservoir pressure to total reservoir pressure was lower at maximal flow than at onset. Subtracted reservoir pressure may contribute to total reservoir pressure to a greater extent in sigmoid neobladders than in other types of neobladder. CONCLUSIONS: 1. Enuresis may have various causes such as external sphincter dysfunction and involuntary contraction of the reservoir. 2. Urine is evacuated not only by abdominal pressure but also by subtracted reservoir pressure in neobladders. 3. Sphincter dyssynergia due to absence of the detrusor muscle may be one cause of dysuria. PMID- 9990226 TI - [The effects of human urine on the adhesion of calcium oxalate crystal to renal tubular cells]. AB - PURPOSE: We examined the effects of human urine on the adhesion of calcium oxalate monohydrate (COM) crystals to Madin-Darby canine kidney (MDCK) cells in vitro. METHODS: Quantitative assay of COM crystal adhesion to MDCK cells: MDCK cells were exposed to COM crystal suspension for 5 minutes. Various urine samples were added in the COM crystal suspension. The adherent COM crystals on the MDCK cells were dissolved by 5 N hydrochloric acid. Calcium concentration of the solution was measured by atomic absorption analysis to quantify the volume of adherent COM crystals. This assay was applied for the experiments as follows. (1) Effect of human urine on COM crystal adhesion. (2) To investigate whether human urine inhibited COM crystal adhesion by acting on the crystal surface or on the cell surface. (3) Isolation of the substance from human urine that inhibits COM crystal adhesion. (4) Comparison of the inhibitory activities of the urine between from stone formers and healthy controls. RESULTS AND CONCLUSION: (1) Human urine had a strong inhibitory effect on COM crystal adhesion to MDCK cells. (2) The capacity of human urine to inhibit adhesion of COM crystals to MDCK cells was shown to be mediated by their ability to act on the crystal surface. (3) We isolated a macromolecular fraction (MW 60,000) that had strong capacity to inhibit cellular adhesion of COM crystals through ion exchange and gel filtration chromatography. (4) Nine urine samples from stone formers demonstrated extreme low inhibitory activities, which supposed us that the inhibitory capacity of the urine against crystal adhesion might be one of the risk factors in kidney stone formation. PMID- 9990227 TI - [Magnetic resonance images of hematospermia]. AB - BACKGROUND: We performed MRI (magnetic resonance imaging) in the pelvic region of 70 cases with hematospermia and conducted a study on the abnormal MRI findings to which hematospermia could be attributed. METHODS: We conducted a study on the morphological anomaly and change in the signal intensity in the prostate gland and of the seminal vesicle as well as on the presence or absence of dilation in the plexus venous surrounding the deferent duct or the prostate gland out of the abnormal MRI findings. As for the seminal vesicle, the patients whose seminal vesicle was seen in higher intensity than the prostate gland in T1 weighted images were diagnosed as having hemorrhagic focus and the patients whose seminal vesicle was seen in low intensity both in T1 and T2 weighted images were diagnosed as having fibrosis caused by chronic inflammation. RESULTS: Abnormal MRI findings were seen in 40 out of the 70 cases (57%). Anomaly in the prostate gland was indicated in 6 (9%) cases. Abnormality in the seminal vesicle was indicated in 30 cases (43%) including hemorrhage of seminal vesicle in 25 cases, chronic inflammation in five cases and cyst of seminal vesicle in one case. CONCLUSION: In conducting an examination of the patients with hematospermia, MRI is the noninvasive and reproducible method and it is possible to identify the hemorrhagic region. Therefore, MRI is thought to be useful to identify the causal organs of hematospermia. PMID- 9990228 TI - [A clinical study of decreased bone density in the patients treated with long term luteinizing hormone releasing hormone analogue (LHRH-a)--the risk of iatrogenic osteoporosis due to treatment of carcinoma of prostate]. AB - BACKGROUND: It is well known that androgens play an important role in bone metabolism and male hypogonadism induce osteoporosis. Luteinizing hormone releasing hormone analogue (LHRH-a) which is essential for conservative therapy of prostatic carcinoma (CaP) ultimately reduces circulating testosterone to castration levels. The purpose of this study was to determine the risk of decrease of bone mineral density in men receiving LHRH-a for CaP. PATIENTS AND METHODS: Fifty-three man with CaP aged 63 to 95 years (mean 75.5 years) were included in this study. Seven patients received LHRH-a with estrogen drug, forty six patients received LHRH-a with or without anti androgen drug. To estimate patient's bone density we use the second metacarpal bone density using a microdensitometry method. RESULTS: Blood level of sex hormone of the forty-six patients who were received LHRH-a without estrogen, was the same as that of castration. Patients who were treated more than twelve months had less bone density than patients who were treated less than eleven months. As the duration of medical castration period was prolonged, patients bone density were reduced. Whereas seven patients who received estrogen drug did not find a decrease of bone density regardless of duration of treatment period. CONCLUSIONS: Hypogonadism induced LHRH-a also reduce bone density, so there is a risk of iatrogenic osteoporosis caused by therapy for CaP with LHRH-a. Patients with osteoporosis easily suffer from a much complicated and pernicious bone fracture, so we should measure bone density of male patients same as female treated with LHRH-a for a long-term. PMID- 9990229 TI - [Successful management for chemorefractory testicular cancer with brain and lung metastases. A case report]. AB - This is a report of successful management for a far advanced, chemorefractory testicular cancer patient. A 29-year-old male was referred to our hospital for the treatment of progressive lung metastases with elevated hCG level, which had recurred after complete remission following 3 courses of BEP chemotherapy and progressed after transient partial regression following 2 courses of intensified EP chemotherapy. In addition, a 3 cm in diameter, solitary brain metastasis was detected on CT. First, we performed wedge resection of bilateral pulmonary lower lobe for chemorefractory pulmonary metastases. Histological examination revealed viable embryonal carcinoma identical to the primary one. Thereafter, whole brain irradiation in combination with VIP chemotherapy (etoposide 100 mg/m2, cisplatin 20 mg/m2 and ifosfamide 1200 mg/m2 daily for 5 consecutive days) was carried out to treat brain metastasis. By 2 cycles of VIP therapy and irradiation (36 Gy), partial tumor regression and normalization of hCG level were achieved, leading to salvage surgery of the brain metastasis which histologically proved to be necrosis. Following an additional cycle of VIP therapy, the patient has been free of recurrence 24 months after completion of the treatment. PMID- 9990230 TI - [Two cases of true hermaphrodite: the usefulness of laparoscopic gonadectomy in childhood. A case report]. AB - Laparoscopic operation has been an alternative method in not only adults but children. We presented two children with true hermaphroditism who were performed by open gonadectomy and laparoscopic gonadectomy respectively. Both patients at the age of 4, and 2 years showed karyotypes of 46, XX, and were raised as girls. In the first case left ovary and right ovotestis were revealed by open gonadal biopsy and right ovotestis was removed by open surgery. In another case bilateral ovotestes were revealed by laparoscopic gonadal biopsy and resected by laparoscopic procedure. Laparoscopy was very useful for detecting the gonadal structures to confirm the diagnosis in intersex patients. True hermaphrodite is one of uncommon intersex anomalies, therefore the diagnosis should be made to demonstrate the coexistence of both ovarian and testicular tissues definitely. We estimated laparoscopic gonadectomy in pediatric true hermaphrodite and concluded that laparoscopic gonadectomy was as profitable as open gonadectomy. PMID- 9990231 TI - [A case report of complete inversion of the bladder in an old woman]. AB - A 77-year-old Japanese woman was admitted to our hospital complaining of small urinary volume. Physical examination revealed a light red, edematous, pyriform mass, approximately 7 cm in diameter at the vulva. An orifice posterior to the base of the mass was catheterized and 20 ml of urine was obtained. Roentgenograms of contrast material injection to the orifice demonstrated a space of 20 ml. A diagnosis of complete inversion of the bladder was made. Under epidural anesthesia, attempts were made to reduce the mass through the urethra. The manual reduction proved to be difficult, but was successful by manual compression of the bladder wall and squeezing it back through the urethra, which took approximately 60 minutes. Complete transurethral inversion of the bladder is so rare that not much of the pathogenesis is clarified. In our patient, senility, obesity, multiple labor and surgeries are assumed to have resulted in laxity of the pelvic wall which would be one of the major risk factors for this condition. PMID- 9990232 TI - [Management of invasive carcinoma of bladder and abdominal aortic aneurysm (AAA); technique of radical total cystectomy and simultaneous AAA repair]. AB - BACKGROUND: There is no consensus on the optimal surgical treatment for patients with concomitant invasive carcinoma of bladder and abdominal aortic aneurysm (AAA). We experienced two patients who were treated successfully with simultaneous radical cystectomy and AAA repair. The techniques required for the combined procedure and case reports are discussed. PROCEDURE: The goal of the one stage operation was to minimize the risk of graft infection without compromising postoperative morbidity and mortality secondary to carcinoma of bladder. Initially pelvic lymph node dissection and radical cystectomy were performed. We preferred retrograde cyctoprostatectomy because most of the cystectomy procedure can be performed without opening the peritoneal cavity and the extent of the retroperitoneal dissection can be minimal. A single-stoma ureterocutaneostomy was preferable urinary diversion. Urinary diversions which utilize intestine such as ileal conduit or ileal urinary reservoir may cause contamination of a graft with bowel content and should be avoided. Before or after urinary diversion, aneurysmal resection and a bifurcated graft replacement were performed. The replaced graft was wrapped with the aneurysmal wall. The major omentum was mobilized and fixed in front of the graft, thereby serving as a protective barrier of the graft. A Dacron graft which was sealed with rifampicin-bonding gelatin was used to further reduce the risk of graft infection. RESULT: Two male patients were treated with the one stage radical cystectomy and AAA repair. Single-stoma ureterocutaneostomy and bilateral ureterocutaneostomy were selected as a urinary diversion. No major postoperative complications, except for paralytic ileus in one case, were observed. CONCLUSION: Our experience and reports of others indicate that radical cystectomy and simultaneous AAA repair can be safely performed with less morbidity than staged operations for the management of concomitant invasive carcinoma of bladder and AAA. PMID- 9990233 TI - [Ureterocystoplasty--ureteral augmentation of the urinary bladder]. AB - The method of choice in the surgical treatment of neurogenic dysfunctions of the lower urinary pathways is to use the ureteral wall for augmentation of the urinary bladder. The advantage of the method is that it rules out risks and complications encountered in techniques using an excluded intestinal or gastric segment (mucus formation, metabolic disorders, malignant transformation, uroinfection, urolithiasis). The author presents the case-history of a 28-year old man with a neurogenic bladder due to surgery of meningomyelocele during childhood. PMID- 9990234 TI - [Sex change surgery in transsexuals]. AB - Surgical conversion of sex in transsexuals implies basically removal of the testes or uterus and creation of the opposite genital. At the Urological Clinic of the General Faculty Hospital and First Medical Faculty, Charles University in Prague during the period from 1992-1998 18 male and 29 female transsexuals were operated. In male transsexualism 17 times the technique of inversion of penile skin was used and in one instance sigmoideoplasty. In female transsexualism 17 metaidoioplasties were made, three plastic operations of the neophallus from inguinal skin flaps and 25 reducing mammaplasties. PMID- 9990235 TI - [Onlay island flap urethroplasty in the treatment of urethral strictures]. AB - A skin island flap was used to create a neourethra in 65 patients aged 2 to 66 years with prolonged or multiple stricture of the anterior urethra. Before, all patients were treated repeatedly and unsuccessfully by open or endoscopic surgery. The principle of the used onlay technique was to supplement the missing lumen of the urethra by an island, usually preputial flap. In case of as missing segment of the urethra the original inlay-onlay technique was applied. After a mean follow-up period of 27 months 12 complications (18.4%) were recorded, six strictures of the proximal anastomosis, three fistulas and three dehiscences of the glans. CONCLUSION: The onlay island flap urethroplasty makes it possible to cure prolonged and multiple strictures of the urethra in one stage and with a relatively low complication rate. PMID- 9990237 TI - [Kidney sparing surgery]. AB - From 1988 to 1998 107 nephron sparing surgery have been done for localised renal cell tumor. The age was between 21 to 75. Nephron sparing surgery means removal of tumor consumed part of renal tissue with oncology clean border in healthy renal tissue. Elective indication for nephron sparing surgery is renal cell carcinoma on single kidney or on bilateral function disabled kidneys. In the last years indication for nephron sparing surgery have spread also to patients with both kidneys, who have single extrarenal growing renal cell carcinoma to the diameter 4.5 cm. In our group of follow up patients, within the interval 3 to 96 months from operation we have 96.26% survival without evidence of recurrent renal cell carcinoma. PMID- 9990236 TI - [Nd:YAG laser in the treatment of superficial lesions of the penis]. AB - In surgical treatment of benign and malignant lesions of the penis in addition to radicality also the demand of a favourable cosmetic result is stressed. The presented paper evaluates experience with the use of a Nd:YAG laser in condylomata acuminata and carcinoma of the penis. The author operated 51 men with condylomata acuminata of the glans, in 32 the external orifice of the urethra was affected. Treatment was successful in all patients with very good cosmetic results, relapses occurred in 11 patients. The author treated successfully also five patients with carcinoma of the penis classified as TIS and T1. In none of the patients a relapse was observed after a mean follow-up period of 15.4 months. PMID- 9990238 TI - [A case of high-flow priapism successfully treated with percutaneous selective embolization of the internal pudendal artery]. AB - Relatively rare high-flow priapism is most frequently caused by contusion or direct injury of the cavernous artery with a subsequent uncontrolled inflow of arterial blood into the cavernous bodies. Knowledge of this pathophysiology and the development of intervention radiology made a more selective therapeutic approach possible. The authors present a report on a case of arterial or high flow priapism which was successfully resolved by a minimally invasive approach- percutaneous superselective transcatheter embolization of the internal pudendal artery. PMID- 9990239 TI - [Quality of life in incontinent men after implantation of an artificial urinary sphincter]. AB - The authors implanted to a group of 10 patients incontinent after prostate surgery (on account of BPH and adenocarcinoma) an artificial AMS 800 sphincter. After a mean follow-up period of 29 months they evaluate based on a questionnaire the therapeutic effect and its influence on the patients quality of life as well as the adequacy of the approval procedure of indication on the part of the insurance company as it influences the quality of life. The effect of treatment and influence on quality of life is evaluated without exception very highly while the approval process is evaluated negatively. The authors draw attention to the risk of suicide in mentally otherwise sound subjects due to unsatisfactory solution of urinary incontinence. Correctly indicated treatment by an artificial sphincter can achieve very satisfactory results. The approval procedure must combine medical and rational aspects, it must be however revised, incl. the economic aspects of the system of health services. PMID- 9990241 TI - [Surgical treatment of hydronephrosis]. AB - The objective of the study was to find the most suitable method of surgery of primary hydronephrosis and congestive horseshoe kidney, based on the authors own experience. The result was the finding that plastic resection operations according to Anderson-Hynes and flap operations in long stenoses and horseshoe kidneys meet the demands which are the prerequisite of favourable therapeutic results. PMID- 9990242 TI - [Methods of surgical treatment of advanced hydronephrosis in children]. AB - For the establishment of the therapeutic procedure in advanced hydronephroses the basic criterion is the functional state of their damaged kidney which can be assessed best by scintigraphy. The results of plastic repair of the damaged pelviureteral portion depends on the stage of hydronephrosis and the child's age. The best results were achieved in less damaged kidneys (hydronephroses I and II) in all age groups and in advanced hydronephroses (IV and V) in children under the age of one year. Early assessment of the diagnosis is important for achievement of good results. This is made possible by ultrasound screening. Early surgery can reduce the percentage of nephrectomies. PMID- 9990243 TI - [Urology in Olomouc]. PMID- 9990245 TI - Delusions and delusional disorders--Part II. PMID- 9990244 TI - [A few observations on surgical technique in transvesical prostatectomy]. PMID- 9990246 TI - Parasomnias. PMID- 9990247 TI - Relapse and expressed emotion. PMID- 9990248 TI - Lithium prevents suicide. PMID- 9990249 TI - Dissociation and sexual abuse. PMID- 9990250 TI - Culture and eating disorders. PMID- 9990251 TI - Placebos and relapse in depression. PMID- 9990252 TI - How does religious faith contribute to recovery from depression? PMID- 9990253 TI - Cytology of Ki-1-positive anaplastic large cell lymphoma. A report of two cases. AB - BACKGROUND: Ki-1-positive anaplastic large cell lymphoma (Ki-1 ALCL), one of the more recently described pleomorphic types of lymphoma, affects mostly children and adolescents and is sometimes mistaken for carcinoma or sarcoma. CASES: Two cases of Ki-1 ALCL were diagnosed on cytology. One patient presented with generalized lymph-adenopathy and involvement of the skin and subcutis, while the other was admitted with pneumonia and multiple subcutaneous masses in the chest wall. Fine needle aspiration cytology smears in both cases showed dissociated cells with abundant, lightly basophilic, vacuolated cytoplasm; oval, round or lobulated nuclei; and binucleate, trinucleate and multinucleate cells with a wreathlike arrangement of nuclei. Most of the tumor cells expressed immunocytologic reactivity to CD 30, and a cytologic diagnosis of Ki-1 ALCL was made. Tru-cut biopsy of the chest wall tumor in case 2 and review of lymph node biopsy done one year previously in case 1 permitted a cytohistologic correlation. CONCLUSION: Knowledge of the distinctive cytomorphologic features of Ki-1 ALCL combined with the clinical setting should enable its distinction from other pleomorphic neoplasms in most cases, while in others it should go a long way toward narrowing the cytologic differential diagnosis. PMID- 9990254 TI - Ossifying fibromyxoid tumor misdiagnosed as follicular neoplasia. A case report. AB - BACKGROUND: Fine needle aspiration of an ossifying fibromyxoid tumor (OFMT) at a prethyroidal location is initially misinterpreted as follicular neoplasia. Though the histopathologic criteria have been analyzed in detail, no experience with the cytologic features of OFMT is reported in the literature. CASE: A 50-year-old male presented clinically with a recurrent goiter. Aspiration cytology (Giemsa stained) was characterized by a predominant fine fibrillary, pink matrix and moderate cellularity. The nuclei were eccentrically located, round to oval and slightly plemorphic, with fine chromatin. Focally, mild nuclear crowding and a few rosettelike structures were present. CONCLUSION: The cytologic features were consistent with a soft tissue tumor of probably neurogenic origin, like OFMT. Differential diagnosis in this particular location not only included follicular thyroid neoplasms but also neurofibroma, neuroma, chondroma and, less likely, neuroepithelial tumors. However, since some diagnostic criteria of OFMT, like the nodular growth pattern and mature bone, can be found only histologically, the diagnostic value of aspiration cytology seems to be limited. PMID- 9990255 TI - Aspiration biopsy cytology of malignant hemangiopericytoma metastatic to the lungs. Cytomorphologic and immunocytochemical study of a case. AB - BACKGROUND: Hemangiopericytoma (HP) is an uncommon, slowly growing tumor that originates in "pericyte" cells. Biologically it can be benign or malignant; however, it is difficult to predict tumor behavior based on histomorphology alone. The cytomorphology of this tumor has been described only rarely. Other spindle cell mesenchymal tumors can mimic HP on fine needle aspiration biopsy (FNAB). CASE: A 60-year-old man presented with cough and a left lung mass on chest roentgenography and multiple smaller bilateral lung nodules on computed tomographic scan. FNAB of the dominant left lung mass showed a moderately cellular aspirate with clusters and single spindle-shaped cells morphologically similar to those of hemangiopericytoma excised from the posterior part of the neck 11 years previously. With immunocytochemical studies, the tumor cells were negative for cytokeratin, factor VIII-related antigen, S-100 protein and HHF35 but positive for vimentin and CD34. CONCLUSION: FNAB is a valuable tool in evaluating nonepithelial metastatic lung tumors. In the appropriate clinical setting, it is possible to render a diagnosis of HP on FNAB in patients with previously documented HP based on morphologic comparison and ancillary studies, especially immunocytochemical stains. PMID- 9990256 TI - Fine needle aspiration diagnosis of combined hepatocellular carcinoma and cholangiocarcinoma. A case report. AB - BACKGROUND: The finding of a dual cellular population in a liver fine needle aspirate, in the appropriate clinical context, raises many differential diagnoses, including combined hepatocellular carcinoma and cholangiocarcinoma, a relatively rare form of primary liver carcinoma. CASE: A hepatitis C-positive patient with cirrhosis and rapidly worsening liver failure underwent fine needle aspiration of two radiologically detected liver masses. Abundant material composed of two cell populations, one typical of hepato-cellular carcinoma and one with features of mucin-producing adenocarcinoma, were found. Both components were positive for low molecular weight cytokeratins, the hepatocellular carcinoma component was positive for carcinoembryonic antigen (CEA) (B18 isoform) in a typical canalicular pattern, and the cholangiocarcinomatous component was positive for high molecular weight cytokeratins and CEA (isoforms B18 and D14). Both components were negative for alpha-fetoprotein. CONCLUSION: Identification of a dual cell population, such as this, in a liver fine needle aspirate should raise the possibility of a combined hepatocellular carcinoma and cholangiocarcinoma and is unlikely to represent metastatic disease. This variant of hepatocellular carcinoma is rare and constitutes 1-5% of primary liver carcinomas. It is important to make this diagnosis and to separate this tumor from the usual hepato-cellular carcinoma and metastatic carcinoma, since it may give rise to pure cholangiocarcinomatous metastatic deposits, adding to the diagnostic difficulties. PMID- 9990257 TI - Fine needle aspiration cytology of undifferentiated (embryonal) sarcoma of the liver. A case report. AB - BACKGROUND: Undifferentiated (embryonal) sarcoma of the liver (UESL) is a rare malignant mesenchymal hepatic tumor with an incidence among liver tumors of 27.7%. It occurs predominantly in children under the age of 15. CASE: The cytologic findings in a case of UESL in fine needle aspiration biopsy material in a 12-year-old girl are described. The patient presented clinically with upper abdominal pain and a palpable mass in the right hepatic lobe. Cytologic features included a combination of polygonal and spindle cells. The polygonal cells were large, with round or lobulated nuclei, and occasionally multinucleated, with one or several nucleoli and variable cytoplasm with poorly defined borders. A few intracytoplasmic and extracytoplasmic eosinophil globules were observed. Histologic and immunohistochemical studies were performed, and staining for vimentin and alpha-1 antichemotrypsin was positive. CONCLUSION: It is important to recognize the cytologic features of this type of liver tumor since rapid diagnosis and initiation of early treatment may improve the poor prognosis of these neoplasms. PMID- 9990258 TI - Cytologic diagnosis of a primary pure oat cell carcinoma of the bladder in voided urine. A case report. AB - BACKGROUND: The urinary bladder is an uncommon site for primary oat cell carcinoma, with as few as 30 histologically diagnosed cases described in the literature. The first reported cytologic diagnosis was made in 1991. CASE: A 76 year-old female presented with gross hematuria. Voided urine cytology showed small, dark cells with little visible cytoplasm and coarse chromatin. Subsequent histopathologic, immunopathologic and electron microscopic studies confirmed the diagnosis of primary oat cell carcinoma. CONCLUSION: The diagnosis of oat cell carcinoma is well recognized in respiratory cytology. The same cells found in a urinary specimen may suggest a primary oat cell tumor in conjunction with negative clinical and radiologic investigations for a primary tumor elsewhere. PMID- 9990259 TI - Mammary carcinoma with osteoclastlike giant cells cytologically mimicking benign breast disease. A case report. AB - BACKGROUND: Mammary carcinoma with osteoclastlike giant cells (OCLGCs) is a rare tumor. Few reports on the fine needle aspiration (FNA) findings are available. This case had cytologic findings overlapping with benign breast disease. CASE: A 50-year-old woman presented with multiple masses in her right breast and a 2-cm right axillary lymph node. Cytologic scrapings and FNA of the same breast mass showed large cohesive, two-dimensional epithelial cells with a uniform distribution of small, bland nuclei. Discohesion, single cells with features of malignancy, cytologic atypia and mitosis were lacking. Many OCLGCs were present. CONCLUSION: The cytologic features of this rare type of breast carcinoma need to become familiar to pathologists to avoid a false negative diagnosis. PMID- 9990260 TI - Aspiration cytology of lung metastasis of monophasic synovial sarcoma. Report of a case. AB - BACKGROUND: Synovial sarcoma usually arises in the extremities of young adults and metastasizes in about 50% of the cases. Fine needle aspiration can reveal those metastases. CASE: A 65-year-old female presented with a solid mass in the left lung from which a fine needle aspirate was taken. Five years earlier her left foot was amputated because of a diagnosis of synovial sarcoma. Aspiration cytology from the lung revealed numerous groups of spindle cells with scant cytoplasm and ovoid nuclei with fine, homogeneous chromatin. Only vimentin was positive. Based on the clinical, cytologic and immunocytochemical studies, a metastasis from synovial sarcoma was considered to be the most accurate cytologic diagnosis. CONCLUSION: This case demonstrates the utility of aspiration cytology in the diagnosis of a metastatic tumor, especially in those organs in which a core or open biopsy might be too aggressive. PMID- 9990262 TI - Cytology of ascitic fluid in a patient with metastasizing malignant Brenner tumor of the ovary. A case report. AB - BACKGROUND: Transitional cell ("Brenner") tumors represent about 2% of all ovarian neoplasms. Brenner tumors are almost always benign. Malignant Brenner tumors of the ovary resemble urothelial carcinomas and are extremely rare. CASE: A 77-year-old, white female presented with malignant Brenner tumor in both ovaries as well as lung and abdominal metastases. The cytology of the ascitic fluid revealed many activated mesothelial cells and three-dimensional cell clusters arranged in a papillary pattern. The round to oval nuclei displayed mild anisokaryosis and hyperchromasia but had a quite evenly dispersed opaque or finely granular nucleoplasm. Enfoldings of the nuclear membrane gave them the appearance of so-called coffee bean nuclei. The cytoplasm stained light bluish. CONCLUSION: Knowledge of the cytologic features of ascitic fluid might allow a preoperative diagnosis of malignant, or at least proliferating, ovarian Brenner tumor. PMID- 9990261 TI - Rhabdomyosarcoma of the urachus. A case report. AB - BACKGROUND: Rhabdomyosarcoma of the urachus is extremely rare, and only two cases have been reported. Cytologic, histologic, immunochemical and electron microscopic findings in embryonal rhabdomyosarcoma of the urachus are presented. CASE: Embryonal rhabdomyosarcoma of the urachus developed in a 2-year-old boy. Imprint smears prepared prior to a histologic examination for a rapid report contained many malignant cells isolated or in clusters in a myxoid background. They were uniformly small, with round to oval nuclei and scant cytoplasm, and immunohistochemically positive for desmin and alpha-sarcomeric muscle actin but negative for myoglobin. This tumor was diagnosed cytologically as embryonal rhabdomyosarcoma because of its skeletal muscle origin and because of its similarity to one of the so-called small round cell tumors of childhood. Histologic examination confirmed the cytologic diagnosis. CONCLUSION: Cytologic, histologic and electron microscopic findings were identical to those described previously for embryonal rhabdomyosarcoma at other sites. In immunochemical examinations, cytologic samples fixed in ethanol are more useful than histologic ones fixed in formalin. Then, in order to differentiate poorly differentiated rhabdomyosarcoma from other small round cell tumors in children, desmin and alpha sarcomeric actin, rather than myoglobin, are recommended. PMID- 9990263 TI - Porocarcinoma detected by fine needle aspiration biopsy of a node metastasis. A case report. AB - BACKGROUND: Porocarcinomas were first reported by Pinkus and Meherengan in 1963 as uncommon malignant adnexal tumors of the skin characterized by epidermotropism with pagetoid diffusion within the epidermis. CASE: The cytologic findings of an eccrine porocarcinoma lymph node metastasis in a 65-year-old female and histologic features of the skin recurrence are reported. Metastasis was firstly identified by fine needle aspiration biopsy (FNAB) performed on one inguinal lymph node. Cytologically the tumor was characterized by atypical malignant cells showing clear granular or keratinized cytoplasm and vesicular nuclei, with prominent nucleoli, which were irregularly dispersed or forming nests or cords, sometimes harboring central necrosis. The skin metastasis, detected after the cytologic FNAB diagnosis, showed superficial dissemination within the epidermis and dermal invasion. CONCLUSION: Cytologic diagnosis of porocarcinoma metastases by FNAB is important for adequate treatment, but adherence to strict diagnostic criteria is necessary. The tumor cells could be histogenetically related to the intraepidermal duct cells of the eccrine sweat glands, and pagetoid diffusion is considered a sort of homing phenomenon. PMID- 9990265 TI - Cutaneous blastomycosis. Report of a case with diagnosis by fine needle aspiration cytology. AB - BACKGROUND: Blastomycosis is rare in India. Clinically, cutaneous blastomycosis may be mistaken for keratoacanthoma, squamous cell carcinoma, tuberculosis, tertiary syphilis, leprosy or pyoderma. CASE: A 19-year-old male presented with a soft, fluctuant swelling at the medial canthus of the eye. Fine needle aspiration biopsy (FNAB) showed many single, spherical structures with thick walls. They had basophilic protoplasm and six nuclei in the center. A few of them showed budding with a broad base. CONCLUSION: The cytomorphology of Blastomyces dermatitidis is characteristic, and the organism can be differentiated from other yeast forms. The disease is sensitive to antifungal imidazole derivatives and can be cured. PMID- 9990264 TI - Cytologic clues for distinguishing the tall cell variant of thyroid papillary carcinoma. A case report. AB - BACKGROUND: In contrast to typical papillary carcinoma, the tall cell variant (TCV) of thyroid papillary carcinoma has more aggressive biologic behavior. Attempts to make a specific diagnosis of TCV of papillary carcinoma based on fine needle aspiration cytology (FNAC) have been unsatisfactory. CASE: The cytologic and histologic study of one such case was made with an emphasis given to identifying the main histologic criteria for the specific diagnosis of TCV of papillary carcinoma in FNAC smears. "Tall cells" were defined as cells with abundant eosinophilic, elongated cytoplasm; the height of these cells was twice their width or more, and they have to constitute > 30% of the tumor cell population. Tall cells were not found in smears of 20 cases of nonaggressive papillary carcinomas investigated as control cases. Only one mitotic figure was found in one slide of one of the control cases (5%) in comparison to two and three mitotic figures found in the two slides of TCV of papillary carcinoma. CONCLUSION: In addition to conventional cytologic features of typical papillary carcinoma, the identification of both tall cells and mitotic figures in the same smears is highly indicative of TCV of papillary carcinoma. More studies will be necessary to confirm the usefulness of this clue. PMID- 9990266 TI - Fine needle aspiration biopsy of a small round cell tumor exhibiting both neural and myogenic differentiation. A case report. AB - BACKGROUND: Divergent differentiation may not be detected in the limited material available in a fine needle aspiration biopsy (FNAB). CASE: A small round cell malignancy showed neural features ultrastructurally on FNAB, in keeping with primitive neuroectodermal tumor, but desmin and actin positivity on surgical biopsy, suggesting rhabdomyosarcoma. CONCLUSION: Accurate classification of small round cell tumors by FNAB is more likely to occur when both electron microscopy and immunocytochemistry are employed since these tumors may express divergent differentiation. PMID- 9990267 TI - Fine needle aspiration cytologic appearance of inflammatory pseudotumor of the liver. A case report. AB - BACKGROUND: Inflammatory pseudotumor (IPT) is a rare space-occupying lesion of the liver that can be clinically confused with a malignant process. CASE REPORT: A 28-year-old male presented with fever and a palpable, firm liver. Ultrasonography and computed tomography revealed a mass in the right lobe of the liver. Fine needle aspiration biopsy (FNAB) under ultrasonographic guidance showed inflammatory cells, fibroblasts and a few hepatocytes. A diagnosis of inflammatory pseudotumour was suggested and confirmed on a true-cut biopsy. CONCLUSION: The cytologic appearance of IPT is characteristic. FNAB under ultrasonographic is a quick and easy technique for its diagnosis and differentiation from malignant space-occupying lesions. PMID- 9990268 TI - Apocrine cells in a fine needle aspirate of gynecomastia. A case report. AB - BACKGROUND: Apocrine cells are a common finding in female mammary cysts, while only rare cases of apocrine metaplasia in gynecomastia have been found in surgical specimens. CASE: A 65-year-old male presented with painful, monolateral gynecomastia. Fine needle aspiration biopsy showed sheets of large, eosinophilic epithelial cells. On immunocytochemistry these cells were positive for apocrine marker GCDFP-15. The patient had ischemic heart disease and was under treatment with spironolactone. CONCLUSION: Apocrine cysts in gynecomastia are rare histologic findings, and this is the first case diagnosed by fine needle aspiration. The finding of apocrine cells confirms the nonneoplastic nature of the lesion, avoiding surgical excision. PMID- 9990269 TI - Cytologic detection of metastatic malignant melanoma in urine. A report of three cases. AB - BACKGROUND: The presence of melanoma cells in urinary specimens is a rare event in either primary or metastatic melanoma of the genitourinary tract. CASES: Melanoma cells were observed in urinary specimens from three white males aged 50, 67 and 51 years, with a previous history of cutaneous melanoma in the first two cases; in the last one autopsy showed a primary melanoma of the gallbladder. The first patient, treated with palliative therapy, survived 10 months, the second died a few days after the cytologic diagnosis, while the third survived 1 month. All patients had widespread metastases at the time of cytologic diagnosis. CONCLUSION: The presence of melanoma cells in urinary specimens may be an important marker for assessing the spread of metastatic disease. When the cytologic diagnosis is made, widespread dissemination is present, and only palliative treatment is suggested. PMID- 9990270 TI - Correlation of cytologic and histologic findings in fibrosing thyroiditis. A case report. AB - BACKGROUND: Fibrous thyroiditis is the rarest form of thyroiditis. Consequently, needle aspiration biopsy experience is limited. Aspirates generally yield paucicellular smears with, at the most, only occasional, small fragments of connective tissue. CASE: A 35-year-old man presented with a firm right thyroid mass. Aspiration yielded cellular smears with round and irregularly shaped, cellular aggregates. Coarse cytoplasmic granules and intranuclear inclusions were also noted. The lesion was surgically excised, and pathologic examination was consistent with fibrous thyroiditis. CONCLUSION: As confirmed by histopathologic examination, the aspirated atypical cellular aggregates represented thyroid follicular units that were distorted by entrapment within fibrous tissue. Fibrosing thyroiditis may yield an atypical smear pattern. PMID- 9990271 TI - Fine needle aspiration cytology of small cell neuroendocrine carcinoma of the breast. A case report. AB - BACKGROUND: Neuroendocrine tumors, usually small cell (oat cell) carcinomas, are almost always primary in the lungs and are highly malignant. Similar tumors have recently been described to occur in various extrapulmonary sites, such as the uterine cervix and prostate. We report a primary neuroendocrine carcinoma of the breast in a female first diagnosed by fine needle aspiration biopsy (FNAB). Search of the literature revealed only three other reports of small cell carcinoma of the breast, one in a male and two in a female, thus making this the third documented case of neuroendocrine carcinoma of the breast in a female. CASE: A 45-year-old, black female presented with a firm, nontender mass at the tail of her left breast. FNAB showed atypical epithelial cells with pale nuclei and inconspicuous nucleoli. An excisional biopsy performed one week later showed microscopically a predominantly solid and syncytial pattern of small cells that appeared spindly in places. It had a high mitotic count, and the stroma was rich in lymphocytes and plasma cells. Immunohistochemical and ultrastructural studies confirmed the diagnosis. CONCLUSION: Small cell (neuroendocrine) mammary carcinoma is a rare entity but does occur and can be diagnosed by FNAB. It does not differ essentially from other mammary neoplasms with regard to prognosis. PMID- 9990272 TI - Osteoclastomalike anaplastic carcinoma of the thyroid gland diagnosed by fine needle aspiration cytology. Report of two cases. AB - BACKGROUND: Thyroid diseases are common among the female population in Iran; the main one is endemic colloid goiter. Thyromegaly can be due to neoplastic and nonneoplastic disorders. The clinical distinction between benign and malignant tumors of the thyroid gland is sometimes difficult. Fine needle aspiration (FNA) study can be used as a preliminary step for identifying such lesions. CASES: Two female patients aged 54 and 62 years were admitted to Nemazi Hospital, Shiraz, Iran, with the chief complaint of weight loss, rapid enlargement of the thyroid gland for the last few months and pressure symptoms in the neck. Clinically these cases were diagnosed as malignant thyroid lesions. However, for further diagnosis the tumors were aspirated. The smears revealed numerous osteoclastlike giant cells with intranuclear inclusions and numerous, isolated oval to spindle-shaped malignant cells. The smears were diagnosed as osteoclastlike anaplastic carcinoma of the thyroid. CONCLUSION: FNA is useful in the diagnosis of osteoclastomalike anaplastic carcinoma of the thyroid. PMID- 9990273 TI - Diabetic mastopathy. A report of two cases diagnosed by aspiration cytology. AB - BACKGROUND: Diabetic mastopathy (DM) is a lymphocytic mastitis that develops in women who have suffered from insulin-dependent diabetes mellitus for some years. CASES: A 51-year-old female with type 1 insulin-dependent diabetes for 13 years presented with a 3-cm, hard, mobile nodule in the right breast. A 59-year-old female on insulin therapy for five years presented with a 4-cm mass in the subareolar region of the breast. The aspirate in both cases showed clusters of ductal cells, some lymphocytes and epithelioid fibroblasts in fragments of dense connective tissue. CONCLUSION: The expected frequency of this disease is far lower than the number of cases diagnosed. This is due to the lack of highly specific criteria for the diagnosis. Only the integration of clinical histories with cytologic findings can lead to an accurate diagnosis and avoid needless surgery. PMID- 9990274 TI - Florid melanocytic colonization in a metastasis of breast carcinoma. A case report. AB - BACKGROUND: Melanocytic colonization in breast carcinoma with skin invasion is an unusual entity. Very rarely does florid colonization by melanocytes simulate melanoma. This phenomenon requires recognition. The cytomorphology of this lesion is reported below for the first time. CASE: A 45-year-female operated on for breast carcinoma developed a recurrent nodule on the mastectomy scar and another circumscribed, depigmented nodule on the back. Fine needle aspiration cytology smears from the recurrent nodule showed features of lobular carcinoma of the breast, whereas the nodule on the back showed cytomorphologic features simulating melanoma along with cells simulating lobular carcinoma of the breast. CONCLUSION: We report for the first time the cytologic finding of melanocytic colonization in subcutaneous secondary breast carcinoma. PMID- 9990276 TI - Aspiration cytology features of the warthin tumor-like variant of papillary thyroid carcinoma. A report of two cases. AB - BACKGROUND: Warthinklike tumor of thyroid is a recently described variant of papillary thyroid carcinoma characterized histologically by a papillary architecture, oxyphilic tumor cells and extensive, chronic inflammation. CASES: Fine needle aspiration was performed on solitary thyroid nodules in two females aged 19 and 35 years. Both patients complained of neck lumps, and the older one noted several months of fatigue and weight gain. The specimens were cytologically similar and were characterized by two distinct sets of features, one suggesting the tall cell or oxyphilic variant of papillary thyroid carcinoma and the other suggesting chronic lymphocytic (Hashimoto's) thyroiditis. Neoplastic follicular cell nuclei were divided into those with grooves, pseudoinclusions and hyperlobation consistent with papillary thyroid carcinoma, while other tumor nuclei exhibited a uniform, round contour; hypergranular chromatin; and relatively prominent nucleoli reminiscent of Hurthle cells. Chronic inflammation was abundant and intimately associated with neoplastic cell groups. CONCLUSION: Warthinlike tumor of the thyroid possesses cytoplasmic and nuclear features with overlap with several other thyroid lesions. Although a definitive diagnosis at aspiration biopsy may be very difficult, the lesions are recognizably neoplastic and identifiable as probable or definite papillary thyroid carcinoma. PMID- 9990275 TI - Cytologic features of fine needle aspirates of papillary and mucoepidermoid carcinoma of the thyroid with anaplastic transformation. A case report. AB - BACKGROUND: Papillary carcinoma is the most common type of thyroid cancer. Cases of papillary carcinoma merging with squamous carcinoma, mucoepidermoid carcinoma, insular carcinoma, columnar cell carcinoma, poorly differentiated carcinoma, anaplastic carcinoma and medullary carcinoma have been reported to date. CASE: A 62-year-old female presented with a 3-cm, hard and painful tumor in the right lobe of the thyroid gland. Fine needle aspiration biopsy yielded a diagnosis of undifferentiated (anaplastic) carcinoma. The tumor was deemed a papillary and mucoepidermoid carcinoma of the thyroid with anaplastic transformation on histology. On retrospective review, the aspirates showed cytologic features of papillary, mucoepidermoid and anaplastic carcinoma. Cellular sheets showing a combination of squamous and mucin-producing features and microcystic like pattern containing hyaline bodies and/or amorphous material correlated well with the histologic and ultrastructural features of mucoepidermoid carcinoma. To our knowledge, no other case with these cytologic characteristics has been reported previously. CONCLUSION: This case illustrates that fine needle aspiration biopsy can be used to recognize rare malignant thyroid neoplasms showing a combination of papillary, mucoepidermoid and undifferentiated carcinoma. PMID- 9990277 TI - Aspiration cytology of 131I-induced thyroiditis. A case report. AB - BACKGROUND: Fine needle aspiration (FNA) has become an indispensable diagnostic tool for the investigation of thyroid nodules. Although 131I may induce morphologic changes similar to those associated with external radiation, a known diagnostic pitfall, the cytology literature on the subject is very sparse. This case exemplifies the thyroid cytologic changes associated with 131I exposure. CASE: A 50-year-old male with a remote history of 131I exposure had an indurated thyroid on routine physical examination. FNA was interpreted as positive for malignant cells, and subsequently a total thyroidectomy was performed. Review of the cytologic sample revealed follicular cells with focal, marked cytologic atypia, abundant colloid, stromal fragments, and lymphocytes. The thyroidectomy specimen consisted of an indurated and nodular gland showing architecture distortion by micronodule formation, lymphocytic infiltrates, interstitial fibrosis and follicular atrophy. Marked nuclear atypia was seen in the follicular cells. CONCLUSION: FNA of thyroid glands exposed to 131I may show significantly large, atypical follicular cells in addition to classical changes of nodular goiter and/or chronic lymphocytic thyroiditis. Although the clinical history and the diffuse nature of the process may favor a benign process in most cases, the presence of marked atypia could lead to a malignant diagnosis. Pathologists, therefore, should exercise extreme caution in interpreting cases with 131I exposure. PMID- 9990278 TI - Fine needle aspiration diagnosis of fibromatosis colli. A report of three cases. AB - BACKGROUND: Fibromatosis colli, a common cause of congenital muscular torticollis, should be differentiated from other neck masses in infants. Invasive diagnostic and therapeutic measures should be avoided. CASES: Three infants under the age of 2 months presented with neck masses--a clinical suspicion of malignancy, lymphadenopathy and teratoma. The cytologic findings included dyshesive multinucleated skeletal muscle fragments showing degenerative and atrophic changes within a background of scattered reactive fibroblasts. CONCLUSION: Fine needle aspiration biopsy is a safe and rapid method of providing a confirmatory diagnosis of neck masses in infants. PMID- 9990279 TI - Residual ovarian tissue mimicking malignancy in a patient with mucinous carcinoid tumor of the ovary. A case report. AB - BACKGROUND: Mucinous carcinoid tumor of the ovary is an uncommon lesion in reproductive-age women. If a patient status post total abdominal hysterectomy and bilateral salpingo-oophorectomy (TAH-BSO) for this tumor presents with a pelvic mass, recurrence of the tumor must be considered, as must the presence of residual ovarian tissue producing physiologic cysts with mass effect, termed the "ovarian remnant syndrome." Benign ovarian follicle cysts may have cellular atypia and mimic malignancy. CASE: A female, one year status post TAH-BSO for mucinous carcinoid tumor of the ovary, presented with pelvic mass. Clinical and radiologic evidence supported the diagnosis of recurrent tumor. Aspiration biopsy material was compatible with malignancy, and immunocytochemical stains supported a neuroendocrine origin of the cells. Surgical excision and histologic examination of the mass revealed ovarian tissue with features of corpus luteum and follicular cyst. CONCLUSION: Numerous pitfalls exist when considering an unusual tumor. While the patient's history, clinical impressions and immunocytochemistry may strongly suggest malignancy, more common benign entities may mimic malignancy and should be considered in the differential diagnosis. PMID- 9990280 TI - Cytologic diagnosis of isolated pancreatic alveolar hydatid disease with immunologic and PCR analyses. A case report. AB - BACKGROUND: Alveolar hydatid disease (AHD) is a rare and severe parasitic infection caused by the larval stage of the fox tapeworm, Echinococcus multilocularis. AHD mainly involves the liver, and although it may extend progressively to the pancreas, isolated pancreatic localization has not been reported previously. CASE: A 68-year-old white female presented with a multicystic mass in the pancreas. Fine needle aspiration showed some protoscolices, free hooklets and fragments of laminated layer, which are pathognomonic features of echinococcosis. Serologic analyses by an enzyme-linked immunosorbent assay using Em2plus antigen showed high antibody reactivity of the patient's serum, which is indicative of an infection with E multilocularis. Diagnosis was finally confirmed by molecular and immunologic analyses of the cytologic material by polymerase chain reaction and direct immunofluorescence. CONCLUSION: This case illustrates the value of cytology in the identification of echinococcosis, particularly when it involves extrahepatic sites, where the risk of misdiagnosis may be related to its extremely rare occurrence. Precise parasitologic tying of E multilocularis in endemic areas is important. PMID- 9990281 TI - Primary cardiac hydatid cyst in a child. Cytologic diagnosis of a case. AB - BACKGROUND: Echinococcosis is a troublesome disease, particularly common in sheep raising communities and usually caused by the cestode Echinococcus granulosus. Although it has been found in almost every organ, isolated cardiac disease is an exceptional presentation since cardiac involvement occurs in only 0.5-3% of echinococcosis cases. CASE: A case of primary cardiac hydatid cyst occurred in a 4-year-old male. The asymptomatic patient was admitted to the hospital for evaluation of an intracardiac cyst. The lesion was successfully excised by open heart surgery, and a definitive diagnosis was made postoperatively by Giemsa staining of hooklets and scolices in cyst fluid. CONCLUSION: This case is of special interest because of the rare site of the lesion and young age of the patient. Pathologists should be alert to the possibility of this parasite appearing in unusual clinical settings. PMID- 9990282 TI - Fine needle aspiration cytology of fibrous hamartoma of infancy. AB - BACKGROUND: Fibrous hamartoma of infancy (FHI) is an uncommon, benign lesion with a distinctive histologic appearance, usually occurring as a small, rapidly growing soft tissue swelling developing in the first two years of life. Apart from one publication, there appear to be few descriptions of the fine needle aspiration biopsy (FNAB) features of this lesion. Detailed information on the clinical and FNAB findings in a patient with FHI is presented. CASE: An 8-month old female had a firm mass on the posterior aspect of the arm. FNAB produced smears that displayed moderate cellularity, loosely lying and clustered fibroblastic-appearing cells, fatty tissue and collagenous material without evidence of significant nuclear atypia or mitoses. CONCLUSION: In the appropriate clinical setting, if the pathologist performing the microscopic evaluation can be confident that all the tissues with features as described are exclusively from the nodule, it is likely that a confident diagnosis of FHI can be made. PMID- 9990283 TI - Fine needle aspiration cytology of invasive micropapillary carcinoma of the breast. A report of two cases. AB - BACKGROUND: Invasive micropapillary carcinoma is a recently described variant of invasive breast cancer characterized by the formation of micropapillae within clear spaces separated by a fibrocollagenous stroma. Although the histologic features are well described, to the best of our knowledge, the cytologic findings have not been reported. CASES: The fine needle aspiration cytology of two cases of biopsy confirmed invasive micropapillary carcinoma are described and compared to the histologic features. In one case, an additional FNA of a subsequent metastasis is reviewed. CONCLUSION: The cytologic features of invasive micropapillary carcinoma are distinctive and correlate with the histology. Invasive micropapillary carcinoma can be suggested based on the FNA findings of numerous well-formed angular, papillary clusters along with other criteria of malignancy. The cytologic differential diagnosis of invasive micropapillary carcinoma is discussed. PMID- 9990284 TI - Blastomycosis. Report of a case with noninvasive, rapid diagnosis of dermal lesions by the Papanicolaou technique. AB - BACKGROUND: Blastomycosis is a rare fungal infection that occurs most often in young to middle-aged men. A common route of infection is through continued contact with soil, occurring in such occupations as gardening and construction work. The skin and lungs are primarily affected. When the respiratory system is involved, blastomycosis may be misdiagnosed as pulmonary miliary tuberculosis. CASE: A 54-year-old, African American male presented with dry cough and multiple verrucous skin lesions affecting the face, shoulder and legs. Chest roentgenography indicated bilateral lung involvement. The patient died following a short, difficult hospital course. Autopsy revealed verrucous skin lesions with dry, thick, raised margins and central necrosis and umbilication, and severe, diffuse pulmonary involvement clinically and radiologically, resembling miliary tuberculosis. A smear from a leg ulcer stained by the Papanicolaou technique revealed fungi within the giant cells. CONCLUSION: Clinical and radiologic findings alone do not establish the diagnosis of blastomycosis. Respiratory involvement may lead to a misdiagnosis of pulmonary miliary tuberculosis. Sputum and bronchial washing examinations by a laboratory technique are in order. This case indicates that cytologic examination of the exudate from an ulcer may result in a strongly suggestive diagnosis. PMID- 9990285 TI - Diagnosis of recurrent desmoplastic small round cell tumor by fine needle aspiration. A case report. AB - BACKGROUND: Desmoplastic small round cell tumor (DSRCT) is a recently described neoplasm characterized by aggressive biology, occurrence in body cavities, expression of antigens from multiple cell lineages and a specific translocation between chromosomes 11 and 22. Most of the published information on this neoplasm is histologic. The case presented here enabled presentation of the cytomorphologic and immunocytochemical features of aspirated cytologic material obtained from this unique tumor. CASE: The cytologic, histologic, radiologic and clinical features of a DSRCT from a 17-year-old patient are presented. Although the initial diagnosis in this case was made on histology, recurrence was proven by fine needle aspiration biopsy (FNAB). CONCLUSION: The presence of sheets or clusters of small round malignant cells, associated with shards of dense fibroconnective tissue, in FNAB should lead the cytologist to consider the diagnosis of DSRCT. PMID- 9990286 TI - Structural modules in actin-binding proteins: towards a new classification. AB - The number of actin binding proteins for which (part of) the three-dimensional structure is known, is steadily increasing. This has led to a picture in which defined structural modules with actin binding capacity are shared between different actin binding proteins. A classification of these based on their common three-dimensional modules appears a logical future step and in this review we provide an initial list starting from the currently known structures. The discussed cases illustrate that a comparison of the similarities and variations within the common structural actin binding unit of different members of a particular class may ultimately provide shortcuts for defining their actin target site and for understanding their effect on actin dynamics. Within this concept, the multitude of possible interactions by an extensive, and still increasing, list of actin binding proteins becomes manageable because they can be presented as variations upon a limited number of structural themes. We discuss the possible evolutionary routes that may have produced the present array of actin binding modules. PMID- 9990287 TI - Role for NF-kappa B in mediating the effects of hyperoxia on IGF-binding protein 2 promoter activity in lung alveolar epithelial cells. AB - The surface of the pulmonary alveolus is a major target for oxidant injury, and its proper repair following injury is dependent on the proliferative response of the stem cells of the alveolar epithelium, the type 2 cells. In previous studies on the mechanisms controlling this response, we have documented involvement of several components of the IGF system, and mainly of the IGF binding protein-2 (IGFBP-2). We have provided evidence that this binding protein was associated with inhibition of DNA synthesis of type 2 cells exposed to oxidants and that its expression was regulated mostly at the level of transcription. In the present study, we focused on the factors involved in this regulation. From examination of the IGFBP-2 gene promoter sequence which revealed the presence of four potential binding sites for transcription factors of the NF-kappa B/Rel family, we hypothesized that NF-kappa B might be involved in the transcriptional activation of IGFBP-2 in oxidant-exposed cells. Data reported herein demonstrated that NF kappa B activated IGFBP-2 promoter in transient transfection assays, and that exposure of cells to hyperoxia was associated with accumulation of the active form of NF-kappa B. Using gel shift analysis, we documented in O2-treated cells an increased binding to the four NF-kappa B binding sites. We also showed that accumulation of NF-kappa B was associated with a decrease in the inhibitory molecule I kappa B-alpha. Based on the current knowledge on NF-kappa B regulation, it is likely that in a number of situations associated with injury of lung alveolar epithelial cells signaling events involving accumulation of NF kappa B converge to activate IGFBP-2 and to block entry into S phase. PMID- 9990288 TI - Ribonucleotide reductase R2 protein is phosphorylated at serine-20 by P34cdc2 kinase. AB - Ribonucleotide reductase is a rate-limiting enzyme in DNA synthesis and is composed of two different proteins, R1 and R2. The R2 protein appears to be rate limiting for enzyme activity in proliferating cells, and it is phosphorylated by p34cdc2 and CDK2, mediators of cell cycle transition events. A sequence in the R2 protein at serine-20 matches a consensus sequence for p34cdc2 and CDK2 kinases. We tested the hypothesis that the serine-20 residue was the major p34cdc2 kinase site of phosphorylation. Three peptides were synthesized (from Asp-13 to Ala-28) that contained either the wild type amino acid sequence (Asp-Gln-Gln-Gln-Leu-Gln Leu-Ser-Pro-Leu-Lys-Arg-Leu-Thr-Leu-Ala, serine peptide) or a mutation, in which the serine residue was replaced with an alanine residue (alanine peptide) or a threonine residue (threonine peptide). Only the serine peptide and threonine peptide were phosphorylated by p34cdc2 kinase. In two-dimensional phosphopeptide mapping experiments of serine peptide and Asp-N endoproteinase digested R2 protein, peptide co-migration patterns suggested that the synthetic phosphopeptide containing serine-20 was identical to the major Asp-N digested R2 phosphopeptide. To further test the hypothesis that serine-20 is the primary phosphorylated residue on R2 protein, three recombinant R2 proteins (R2-Thr, R2 Asp and R2-Ala) were generated by site-directed mutagenesis, in which the serine 20 residue was replaced with threonine, aspartic acid or alanine residues. Wild type R2 and threonine-substituted R2 proteins (R2-Thr) were phosphorylated by p34cdc2 kinase, whereas under the same experimental conditions, R2-Asp and R2-Ala phosphorylation was not detected. Furthermore, the phosphorylated amino acid residue in the R2-Thr protein was determined to be phosphothreonine. Therefore, by replacing a serine-20 residue with a threonine, the phosphorylated amino acid in R2 protein was changed to a phosphothreonine. In total, these results firmly establish that a major p34cdc2 phosphorylation site on the ribonucleotide reductase R2 protein occurs near the N-terminal end at serine-20, which is found within the sequence Ser-Pro-Leu-Lys-Arg-Leu. Comparison of ribonucleotide reductase activities between wild type and mutated forms of the R2 proteins suggested that mutation at serine-20 did not significantly affect enzyme activity. PMID- 9990289 TI - Low-energy laser irradiation affects satellite cell proliferation and differentiation in vitro. AB - Low-energy laser (He-Ne) irradiation was found to promote skeletal muscle regeneration in vivo. In this study, its effect on the proliferation and differentiation of satellite cells in vitro was evaluated. Primary rat satellite cells were irradiated for various time periods immediately after preparation, and thymidine incorporation was determined after 2 days in culture. Laser irradiation affected thymidine incorporation in a bell-shaped manner, with a peak at 3 s of irradiation. Three seconds of irradiation caused an induction of cell-cycle regulatory proteins: cyclin D1, cyclin E and cyclin A in an established line of mouse satellite cells, pmi28, and proliferating cell nuclear antigen (PCNA) in primary rat satellite cells. The induction of cyclins by laser irradiation was compatible with their induction by serum refeeding of the cells. Laser irradiation effect on cell proliferation was dependent on the rat's age. At 3 weeks of age, thymidine incorporation in the irradiated cells was more than twofold higher than that in the controls, while at 6 weeks of age this difference had almost disappeared. Myosin heavy chain (MHC) protein levels were twofold lower in the irradiated than in the control cells, whereas the proliferation of the irradiated cells was twofold higher. Fusion percentage was lower in the irradiated compared to non-irradiated cells. In light of these data, the promoting effect of laser irradiation on skeletal muscle regeneration in vivo may be due to its effect on the activation of early cell-cycle regulatory genes in satellite cells, leading to increased proliferation and to a delay in cell differentiation. PMID- 9990290 TI - Adhesive and growth properties of lectin from the ascidian Didemnum ternatanum on cultivated marine invertebrate cells. AB - The effects of N-Acetyl-D-glucosamine-specific lectin (M(r) 27 kDa) isolated from the ascidian Didemnum ternatanum on cultivated cells of molluscs and echinoderms were studied. This lectin was found to stimulate the growth or the differentiation of cultivated marine invertebrate cells depending on the stage of embryonic development at which primary cell cultures were obtained. In addition, it has been shown to increase the attachment of cells in primary cultures of these animals. The degree of attachment is considerably increased when collagen or polylysine substrates are used. Using scanning electron microscopy we have demonstrated the stage-specific effect of this lectin on embryonic sea urchin and molluscan cells. Intensive cell spreading and an alteration of cell shape were observed only at the gastrula stage, when the switching from maternal information to embryonic genes occurred. The ascidian lectin seems to have some characteristics of both an adhesive factor and a growth factor. PMID- 9990291 TI - A redox-dependent, G-protein-coupled phospholipase A of the plasma membrane is involved in the elicitation of alkaloid biosynthesis in Eschscholtzia californica. AB - In cultured cells of California poppy formation of benzophenanthridine alkaloids can be triggered by a yeast elicitor preparation independently of the hypersensitive reaction. A plasma membrane (PM) bound phospholipase A (PLA) is likely to play a role in the signalling process: PLA activity was detectable in individual cells, cell suspensions and PM vesicles with the fluorogenic phospholipid bis-BODIPY FL C11-PC and was sensitive to known inhibitors of PLA2. In microscopic assays, enzyme activity increased after elicitor contact of cells that were pretreated with non-saturating concentrations of PLA2 inhibitors. In PM vesicles a PLA2-like protein as well as G alpha- and G beta-proteins were detected immunologically. Anti-G alpha or anti-G beta antisera or mastoparan stimulated PLA activity thus indicating a G-protein-controlled enzyme. Elicitation of alkaloid production was sensitive to aristolochic acid and enhanced by PLA2 products such as lysophosphatidylcholine and linolenic acid. Pretreatment of the cells with the artificial electron acceptors hexabromoiridate(V) or ferricyanide(III) reversibly abolished the effect of subsequent elicitation and reduced the activity of PLA both in intact cells and in PM vesicles. It appears, therefore, that PLA2 is a point of interference of redox control with the signal path. PMID- 9990292 TI - Hepatocyte differentiation of WIF-B cells includes a high capacity of interleukin 6-mediated induction of alpha 1-acid glycoprotein and alpha 2-macroglobulin. AB - Responsiveness to cytokine-mediated acute inflammatory stimuli of the highly differentiated and polarized WIF-B hybrid cell line was studied by measuring the induction of alpha 1-acid glycoprotein and alpha 2-macroglobulin mRNAs after interleukin-1, interleukin-6 and tumor necrosis factor-alpha treatments in the presence of dexamethasone. Compared with their Fao parent, WIF-B cells were 10 times more responsive to 24-h interleukin-6 induction regarding alpha 2 macroglobulin induction. At variance from the response measured in Fao cells, the late effects of interleukin-6 treatment confirmed the higher sensitivity of WIF-B cells to this cytokine as a 72-h treatment as 10 times more effective than a 24-h treatment at inducting alpha 1-acid glycoprotein mRNA. These findings highlight the hepatocyte differentiation of WIF-B cells compared with other hepatoma cell lines, with respect to the regulation of acute-phase protein gene expression. They also make WIF-B cells a convenient model to study the molecular effects of interleukin-6 in terms of transduction and/or transcription, and the many cross talks that occur during the regulation of acute-phase protein gene expression. PMID- 9990293 TI - Alteration of heart uncoupling protein-2 mRNA regulated by sympathetic nerve and triiodothyronine during postnatal period in rats. AB - To provide tissue-specific and developmental characteristics of gene expression of rat heart uncoupling protein-2 (UCP2), we investigated developmental alterations of UCPs mRNA expression in the heart and brown adipose tissue (BAT), and examined possible up-regulators of heart UCP2 expression using in vitro studies. Heart UCP2 mRNA expression was low during the early postnatal days followed by a rapid and significant increase in the 2nd postnatal week. Heart UCP3 mRNA remained undetectable until the 2nd postnatal week when the expression reached a small but significant peak. BAT UCP1 mRNA was abundantly expressed in the neonate, but the expression rapidly decreased to the adult level. The studies using cultured cardiomyocytes demonstrated that both 10(-8) M triiodothyronine and 10(-7) M isoproterenol, but not phenylephrine, increased UCP2 mRNA expression. These results indicate that the sympathetic nervous system and/or thyroid hormones may be involved in the up-regulation of heart UCP2 gene expression during postnatal development. The increase in postnatal heart UCP2 may provide a key link between the postnatal energy shift and adaptation of rat pups to their novel environment. PMID- 9990294 TI - Stimulation of hyaluronan synthesis by tumor necrosis factor-alpha is mediated by the p50/p65 NF-kappa B complex in MRC-5 myofibroblasts. AB - The lesions of fibrocontractive diseases result from an excessive myofibroproliferative response to numerous forms of inflammatory stimuli, which elicit the net deposition of extracellular matrix (ECM) in the interstitium of the affected tissue. Hyaluronan (HA), reported to be a key player supporting cellular migration and adherence, is a major component of ECM that undergoes dynamic regulation during inflammation. The molecular regulation of HA biosynthesis by inflammatory cytokines on myofibroblasts is not yet completely understood. Here we report the biochemical characteristics of the lung myofibroblast cell line MRC-5, and we demonstrate that the production of HA by this cell line is inducible by the proinflammatory cytokine, tumor necrosis factor-alpha (TNF-alpha), at the message level of HA synthase (HAS). In TNF-alpha stimulated MRC-5 cells, DNA-binding and competition experiments indicated that the predominant NF-kappa B binding activity detected with nuclear extract stimulated cells is mediated by the p50/p65 complex. Using antisense oligonucleotides, we confirmed that the TNF-alpha-stimulation of HA synthesis by MRC-5 cells is dependent on the activation of the p50/p65 NF-kappa B complex. These findings indicate that TNF-alpha production within inflamed tissues may enhance the HA synthesis via the transcriptional induction of HAS on myofibroblasts, thereby providing a provisional matrix for supporting cellular migration and adhesion, and that the p50/p65 NF-kappa B complex that plays an important role in the regulation of HA production by TNF-alpha might be an appropriate target for therapeutic compounds to treat tissue fibrosis accompanied by inflammation. PMID- 9990295 TI - NSAIDs and butyrate sensitize a human colorectal cancer cell line to TNF-alpha and Fas ligation: the role of reactive oxygen species. AB - The nonsteroidal antiinflammatory drugs (NSAIDs) indomethacin and salicylic acid and the short chain fatty acid butyrate are effective colon cancer chemopreventive agents that increase reactive oxygen species (ROS) generation in colon cancer cells. Here we demonstrate that these agents sensitize the normally resistant human HT-29 colon cancer cell line to apoptosis induced by TNF-alpha or a Fas ligating antibody. The role of ROS in this sensitization is supported by the finding that direct exposure of the cells to H2O2 is sufficient for sensitization. Neither TNF-alpha nor Fas ligation alter basal or chemopreventive agent-activated ROS generation, suggesting that the death ligands and chemopreventive agents act in a complementary fashion. The dual chemopreventive agent/death ligand treatments do not increase Fas, TNF receptor 1, Bak or c-myc expression (although salicylic acid moderately induces of Fas expression). Cell death does correlate with alterations in NF-kappa B activity: the NSAIDs, butyrate and H2O2 enhance c-Rel complex formation by TNF-alpha and provide an overall enhancement of NF-kappa B activation by Fas. The antioxidant N acetylcysteine (NAC) blocks cell death and NF-kappa B activation induced by Fas ligation, suggesting a potential role for NF-kappa B in Fas-induced apoptosis in these cells. The effects of NAC on TNF-alpha-induced cell death are more complex, with NAC being marginally protective and itself enhancing the formation of c-Rel containing complexes at higher concentrations (25 mM). The influence of NSAIDs and butyrate on ROS generation and death ligand sensitivity may be relevant to their ability to suppress colon carcinogenesis. PMID- 9990296 TI - Myristoylated alanine-rich C-kinase substrate is phosphorylated and translocated by a phorbol ester-insensitive and calcium-independent protein kinase C isoform in C6 glioma cell membranes. AB - Myristoylated alanine-rich C-kinase substrate (MARCKS), a prominent substrate for conventional and novel protein kinase C (PKC) isoforms, is involved in the regulation of membrane-cytoskeletal interactions. Addition of [gamma-32P]ATP to the membrane fraction of digitonin-permeabilized C6 glioma cells resulted in phosphorylation and release of MARCKS, indicating involvement of an active membrane-bound kinase. Pretreatment of cells with 2 microM 4 beta-12-O tetradecanoyl-phorbol-13-acetate (beta-TPA) for 18 h downregulated conventional (PKC alpha) and novel (PKC delta) isoforms of PKC by > 90% in both membrane and soluble fractions, but did not inhibit the rate of ATP-dependent phosphorylation or release of MARCKS, or decrease levels of membrane-bound PKC zeta or PKC mu. MARCKS phosphorylation was inhibited by staurosporine, bis-indolylmaleimide (a PKC-specific inhibitor), Go6983 (inhibits all isoforms except PKC mu), and a peptide from the calmodulin-binding domain of MARCKS, but was unaffected by EGTA or Go6976 (inhibits cPKCs and PKC mu). Peptide mapping indicated similar in vivo and in vitro phosphorylation at serine residue(s) known to be phosphorylated by PKC. These findings support a novel mechanism by which MARCKS may be regulated by an atypical PKC isoform in phorbol ester-downregulated cells. PMID- 9990297 TI - Uptake and intracellular fate of phage display vectors in mammalian cells. AB - Receptor-mediated endocytosis is exploited in experimental systems for selective delivery of genes and drugs into specific cells. To improve targeting efficiency of delivery vectors, we have used phage display technology to isolate novel ligands for endocytosed receptors. We show here that phage vectors internalized by mammalian cells via integrin-mediated endocytosis can be rescued by cell lysis and quantitated by infection of bacteria. Immediately following uptake, phage enter an intracellular compartment where they remain intact, with phage titer unaffected by the addition of chloroquine. Phage are then translocated to a second intracellular compartment in which they are inactivated and their titer affected by chloroquine. Immunofluorescence microscopy showed an association of the second compartment with supranuclear organelles. The ability to recover internalized phage in an infectious form from two distinctive intracellular compartments provides a means to select novel ligands from phage libraries for targeted delivery of macromolecules into mammalian cells. PMID- 9990298 TI - Targeted delivery of multivalent phage display vectors into mammalian cells. AB - Novel peptide motives targeting endocytosing receptors were isolated from phage display libraries of random peptides by recovering internalized phage from mammalian cells. The peptide-presenting phage selected by internalization in HEp 2 and ECV304 human cells were taken up 1000- to 100,000-fold more efficiently than their parent libraries, and from 10 to 100 times faster than phage particles displaying integrin-binding peptides. A high degree of selectivity of phage uptake was observed in these cells: phage selected in ECV304 cells were internalized approximately 100-fold more efficiently in ECV304 cells than in HEp 2 cells. Likewise, phage selected in HEp-2 cells were subsequently taken up approximately 40-fold more efficiently by HEp-2 cells than by ECV304 cells. In multiple independent trials using a cyclic peptide library, an identical peptide sequence displayed on phage was internalized by and recovered from ECV304 cells. These findings indicate that the internalization process is highly selective, and is capable of capturing a specific peptide from 2 x 10(7) peptide variants. Immunofluorescence microscopy showed juxtanuclear localization of internalized phage. These results demonstrate the feasibility of using multivalent phage display libraries to identify new targeting ligands for the intracellular delivery of macromolecules. PMID- 9990299 TI - Tributyltin triggers apoptosis in trout hepatocytes: the role of Ca2+, protein kinase C and proteases. AB - The purpose of the present study was to study the mechanisms involved in the induction of apoptosis and by tributyltin (TBT) in rainbow trout hepatocytes, and to examine the role of intracellular Ca2+, protein kinase C (PKC) and proteases in the apoptotic process. The intracellular Ca2+ chelator BAPTA-AM has a suppressive effect on TBT-mediated apoptosis. However, exposure to the ionophore A23187 is not sufficient to induce apoptosis in trout hepatocytes. The results obtained also show that TBT stimulates PKC gamma and delta translocation from cytosol to the plasma membrane in trout hepatocytes after 30 min of exposure. However, PKC gamma translocation is down-regulated after 90 min of treatment. The addition of protein kinase inhibitors (staurosporine and H-7) not only fails to inhibit apoptosis induced by TBT, but also leads to enhancement of DNA fragmentation. These inhibitors also afford a remarkable protection against the loss of plasma membrane integrity caused by TBT exposure. PMA, a direct activator of PKC, fails to stimulate DNA fragmentation. In addition, Z-VAD.FMK is an extremely potent inhibitor of TBT-induced apoptosis in trout hepatocytes, indicating that the activation of ICE-like proteases is a key event in this process. The cysteine protease inhibitor N-ethylmaleimide also prevented TBT induced DNA fragmentation. Taken together, these data allow for the first time to suggest a mechanistic model of TBT-induced apoptosis. We propose that TBT could trigger apoptosis through a step involving Ca2+ efflux from the endoplasmic reticulum or other intracellular pools and by mechanisms involving cysteine proteases, such as calpains, as well as the phosphorylation status of apoptotic proteins such as Bcl-2 homologues. PMID- 9990300 TI - EGF stimulates tyrosine phosphorylation of focal adhesion kinase (p125FAK) and paxillin in rat pancreatic acini by a phospholipase C-independent process that depends on phosphatidylinositol 3-kinase, the small GTP-binding protein, p21rho, and the integrity of the actin cytoskeleton. AB - Epidermal growth factor (EGF) is a potent mitogen in many cell types including pancreatic cells. Recent studies show that the effects of some growth factors on growth and cell migration are mediated by tyrosine phosphorylation of the cytosolic tyrosine kinase p125 focal adhesion kinase (p125FAK) and the cytoskeletal protein, paxillin. The aim of the present study was to determine whether EGF activates this pathway in rat pancreatic acini and causes tyrosine phosphorylation of each of these proteins, and to examine the intracellular pathways involved. Treatment of pancreatic acini with EGF induced a rapid, concentration-dependent increase in p125FAK and paxillin tyrosine phosphorylation. Depletion of the intracellular calcium pool or inhibition of PKC activation had no effect on the response to EGF. However, inhibition of the phosphatidylinositol 3-kinase (PI3-kinase) or inactivation of p21rho inhibited EGF-stimulated phosphorylation of p125FAK and paxillin by more than 70%. Finally, cytochalasin D, a selective disrupter of the actin filament network, completely inhibited EGF-stimulated tyrosine phosphorylation of both proteins. All these treatments did not modify EGF receptor autophosphorylation in response to EGF. These results identify p125FAK and paxillin as components of the intracellular pathways stimulated after EGF receptor occupation in rat pancreatic acini. Activation of this cascade requires activation of PI3-kinase and participation of p21rho, but not PKC activation and calcium mobilization. PMID- 9990301 TI - Identification and cloning of a novel phosphatase expressed at high levels in differentiating growth plate chondrocytes. AB - Growth plate chondrocytes progress through a proliferative phase before acquiring a terminally-differentiated phenotype. In this study we used Percoll density gradients to separate chick growth plate chondrocytes into populations of different maturational phenotype. By applying agarose gel differential display to these populations we cloned a cDNA encoding a novel 268 amino acid protein (3X11A). 3X11A contains two peptide motifs that are conserved in a recently identified superfamily of phosphotransferases. It is likely that 3X11A is a phosphatase, but its substrate specificity remains uncertain. 3X11A expression is upregulated 5-fold during chondrocyte terminal differentiation and its expression is approximately 100-fold higher in hypertrophic chondrocytes than in non chondrogenic tissues. This suggests that 3X11A participates in a biochemical pathway that is particularly active in differentiating chondrocytes. PMID- 9990302 TI - Evidence for protein splicing in the endoplasmic reticulum-Golgi intermediate compartment. AB - We present evidence that the endoplasmic reticulum-Golgi intermediate compartment (ERGIC) is a site for protein splicing of cathepsin C: (i) maturation of the enzyme in COS 7 cells is a two-step process starting within the ERGIC, and (ii) the intermediately processed polypeptide retains both termini of the proenzyme and lacks an internal fragment. PMID- 9990303 TI - A possible involvement of melanocortin 3 receptor in the regulation of adrenal gland function in the chicken. AB - The melanocortin 3 receptor (MC3-R) in the melanocortin receptor family has been identified as a neural receptor subtype mainly expressed in the brain in mammals. We report here the isolation of the chicken gene for MC3-R, CMC3, displaying different tissue distribution from mammalian counterparts. The CMC3 gene was found to be a single copy gene encoding a 325 amino acid protein, sharing 75.3 76.8% identity with mammalian counterparts. When assessed by RT-PCR, the CMC3 mRNA was not detected in the brain but was exclusively expressed in adrenal glands, where Agouti-related protein/Agouti-related transcript (AGRP/ART), a newly identified endogenous antagonist of MC3-R, is expressed in mammals, raising the possibility that the CMC3 plays a role in complicated regulation of the gland function by melanocortins and AGRP/ART in the chicken. Noteworthy, MC1-R gene was found to be a quite unique member of the chicken MC-R family with regard to GC content and codon usage. It may reflect as yet unidentified evolutionary pressure operating specifically on the gene. PMID- 9990304 TI - Cloning and sequence analysis of two cDNAs encoding cyclin A and cyclin B in the zebra mussel Dreissena polymorpha. AB - Cyclins are key components in the progression of both mitotic and meiotic cell cycle control. Full-length cDNA clones encoding cyclin A and cyclin B were isolated from a zebra mussel testis cDNA library. The clones contained open reading frames of 419 and 434 amino acids, had similarity to cyclins A and B from other species, but also some unique features in their sequences. Cyclin A and B mRNA was expressed in testis, ovary, gill, mantle, muscle, and eggs, as shown by specific polymerase chain reaction. PMID- 9990305 TI - Differential regulation of p27kip1 levels and CDK activities by hypertrophic and hyperplastic agents in vascular smooth muscle cells. AB - To understand the molecular mechanisms that determine the fate of a cell to undergo either hypertrophy or hyperplasia, we studied the effects of angiotensin II (Ang II) and platelet-derived growth factor (PDGF)-BB, hypertrophic and hyperplastic agents, respectively, on the modulation of G1/S transition molecules in smooth muscle cells. Ang II increased protein synthesis while PDGF-BB induced both DNA and protein synthesis. Ang II had no significant effect on the steady state levels of cyclin-dependent kinase (CDK) inhibitor (CDKI), p27kip1, and on the activities of CDK2 and CDK4, although it caused a modest increase in cyclin E levels. In contrast, PDGF-BB induced depletion of p27kip1 and increased cyclins D1 and E levels and CDK2 and CDK4 activities. Reflecting its lack of effect on CDK activities, Ang II failed to phosphorylate tumor suppressor retinoblastoma protein, Rb. PDGF-BB, on the other hand, induced phosphorylation of Rb, consistent with its ability to activate CDKs. Together, these findings suggest that Ang II-induced hypertrophy may be due to its failure to activate cellular signaling events required for G1/S transition. PMID- 9990306 TI - Multiple effects of econazole on calcium signaling: depletion of thapsigargin sensitive calcium store, activation of extracellular calcium influx, and inhibition of capacitative calcium entry. AB - The effect of econazole on intracellular calcium levels ([Ca2+]i) in Madin Darby canine kidney cells was investigated using fura-2 fluorimetry. Econazole increased [Ca2+]i dose-dependently at 5-50 microM. The Ca2+ signal consisted of an initial rise, a gradual decay and a sustained plateau. Extracellular Ca2+ removal partially reduced the econazole response. Mn2+ quench of fura-2 fluorescence confirmed econazole-induced Ca2+ influx. The econazole-sensitive intracellular Ca2+ store overlaps with that sensitive to thapsigargin, an inhibitor of the endoplasmic reticulum Ca2+ pump, because 25 microM econazole depleted the thapsigargin-sensitive store, and conversely, thapsigargin abolished the econazole response. Econazole (25-50 microM) partially inhibited capacitative Ca2+ entry induced by cyclopiazonic acid, another endoplasmic reticulum Ca2+ pump inhibitor, measured by depleting internal Ca2+ store in Ca(2+)-free medium followed by adding 10 mM CaCl2. Econazole induced capacitative Ca2+ entry itself. Pretreatment with La3+ (100 microM) partially inhibited 25 microM econazole induced Mn2+ quench of fura-2 fluorescence, and La3+ immediately reduced 20 microM econazole-induced Ca2+ signal when added at the peak of the signal, suggesting that econazole induced Ca2+ influx via two separate pathways: one is sensitive to La3+, the other is not. La3+ enlarged 25 microM econazole-induced [Ca2+]i transient during the decay phase. The econazole response was not altered when the cytosolic level of inositol 1,4,5-trisphosphate was inhibited by the phospholipase C inhibitor U73122. PMID- 9990307 TI - Integrin alpha IIb beta 3-mediated pp125FAK phosphorylation and platelet spreading on fibrinogen are regulated by PI 3-kinase. AB - Activation of the focal adhesion kinase pp125FAK correlates with its phosphorylation on tyrosine residues and is mediated by multiple receptor-ligand pairs. In platelets, pp125FAK phosphorylation is triggered by alpha IIb beta 3 integrin or Fc gamma RII receptor interaction with immobilized fibrinogen and IgG, respectively. In this study we used platelets as a model system to explore the role of PI 3-kinase relative to pp125FAK phosphorylation. Treatment of the platelets with two PI 3-kinase inhibitors, wortmannin and LY294002, inhibited in a dose-dependent manner alpha IIb beta 3-mediated platelet spreading on fibrinogen having no effect on platelet spreading on IgG. Both inhibitors also completely abolished alpha IIb beta 3-mediated pp125FAK phosphorylation but not pp72syk phosphorylation. Furthermore, Fc gamma RII- and thrombin-induced pp125FAK phosphorylation were not affected by wortmannin and LY294002. Finally, the PI 3 kinase inhibitors' effect on alpha IIb beta 3-mediated spreading and pp125FAK phosphorylation was reversed by phorbol ester treatment. These results establish that the role of PI 3-kinase relative to pp125FAK phosphorylation in platelets is receptor type-specific yet essential for alpha IIb beta 3-mediated cell spreading and pp125FAK phosphorylation. PMID- 9990308 TI - Affinities of mAbs to Tet repressor complexed with operator or tetracycline suggest conformational changes associated with induction. AB - We isolated five monoclonal antibodies (mAbs) made against tetracycline repressor (TetR), one against the TetR tetracycline complex (Tc) and two against the TetR tet operator (tetO) complex. The epitopes of the anti-TetR mAbs are localized in the alpha-helix-turn-alpha-helix motif (HTH), at different sites near the Tc binding pocket and at the dimerization interface. The anti-TetR-Tc and one of the anti-TetR-tetO mAbs recognize epitopes near the Tc binding pocket. The other anti TetR-tetO mAb binds to an epitope within the HTH. Quantitative immunoprecipitation and competitive ELISA employing TetR, TetR-Tc, or TetR-tetO revealed different affinities of the mAbs for TetR in these functional states. Binding of the two mAbs to epitopes in the HTH was identical for TetR and TetR-Tc indicating the same conformation in both forms. The epitope located in the dimerization interface is bound more strongly in TetR compared to TetR-Tc, supporting the idea of different conformations of that epitope in these forms of TetR. The greatest affinity differences were found for epitopes around the Tc binding pocket. Two anti-TetR mAbs have the highest affinities for free TetR, somewhat reduced affinity for TetR-tetO and the lowest affinities for TetR-Tc. The anti-TetR-Tc mAb has a discontinuous epitope, formed in TetR-Tc, which is less well bound in TetR and not bound in the TetR-tetO complex. One anti-TetR tetO mAb does not recognize TetR-Tc. Since the epitopes do not overlap with the respective ligand binding sites on TetR, these results are interpreted as conformational differences of the epitopes in these forms of TetR. PMID- 9990309 TI - Importance of heptameric ring integrity for activity of Escherichia coli ClpP. AB - Radiation target analysis has been used to identify the minimal functional unit for expression of activity of ClpP, the proteolytic component of the ATP dependent ClpAP protease. Radiation target sizes determined for small peptide hydrolysis, for ClpA activated and nucleotide-activated oligopeptide cleavage, and for ClpA-activated ATP-dependent protein degradation were 154, 118, and 160 kDa, respectively. Thus, the hydrolytic activity of ClpP, subunit M, 21,500, is dependent on the native oligomeric structure. The quaternary structure of ClpP determined by electron microscopy and hydrodynamic studies consists of two face to-face seven-membered rings. The radiation target sizes are consistent with a requirement for conformational integrity of an entire ring for expression of hydrolytic activity. Radiation damage led to disruption of inter-ring contacts, giving rise to isolated rings of ClpP. Thus, contacts between rings of ClpP are less stable and more easily disrupted than contacts between subunits within the rings. Our data suggest that cooperative interactions between subunits within the ClpP rings are important for maintaining the active conformation of the proteolytic active site. PMID- 9990310 TI - Two hexameric cyanoprotein subunits from an insect, Riptortus clavatus. Sequence, phylogeny and developmental and juvenile hormone regulation. AB - Hemolymph of a hemipteran insect, Riptortus clavatus, contains four distinct hexameric proteins (cyanoproteins) composed of two distinct subunits, CP alpha and CP beta, which show profiles of abundance depending on developmental stage, diapause status controlled by juvenile hormone, and sex. We have isolated cDNA clones encoding the two subunits and determined the complete sequences. The nucleotide sequences predict polypeptides of 693 and 691 residues for CP alpha and CP beta, respectively, including identical 16-residue signal peptides. The deduced amino acid sequences of both CP alpha and CP beta have significant similarity to other hemocyanin-related proteins, indicating that the cyanoproteins represent hexamerins. Phylogenetic analyses show that the cyanoprotein subunits can be grouped together with other hexamerins from exopterygote insects. Developmental Northern-blot analyses suggest that the expression of the cyanoproteins is regulated at the level of transcript abundance. In addition, the expression of the CP alpha subunit in female adults has been shown to be enhanced by juvenile hormone (JH) while the expression of the CP beta subunit is suppressed by the same hormone. To our knowledge, the CP alpha subunit of R. clavatus is the first case of a JH-enhanceable hexamerin whose sequence has been determined. PMID- 9990311 TI - Mutational analysis of chitin synthase 2 of Saccharomyces cerevisiae. Identification of additional amino acid residues involved in its catalytic activity. AB - Saccharomyces cerevisiae harbors three chitin synthases termed Chs1p, Chs2p and Chs3p. Previously, we demonstrated that con1, a region that is highly conserved among all chitin synthases, contains amino acids essential for the catalytic activity of the enzyme and that Asp562, Gln601, Arg604, and Trp605 found in con1 together with Asp441 were probable catalytic sites of the enzyme. Here we report that another region, con2, in the C-terminal half of Chs2p is also conserved exclusively in chitin synthases that resemble S. cerevisiae Chs1p and Chs2p. Alanine substitutions for the conserved amino acids in con2 identified five amino acids, Asn797, His799, Asp800, Trp803, and Thr805, the mutation of which severely diminished enzymatic activity and the enzyme's ability to rescue the yeast chs2 delta chs3 delta null mutant strain. Although the activities of some of the mutant enzymes were too low to measure enzyme kinetics, most of the alanine mutations in con2 affected the kcat values rather than the K(m) values. Whereas a conservative mutation of Asn797 restored the activity, those of His799, Asp800, Trp803, and Thr805 did not. A fine alignment of the amino acid sequences of con2 and Chs3p revealed that Asp800, Trp803 and Thr805 are completely conserved near the C-terminal ends of Chs3p and its homologs in other fungi. On the basis of these findings, we propose that Asp800, Trp803, and Thr805 in con2 are additional residues involved in catalysis, and hypothesise that Asp800 together with the previously identified Asp441 and Asp562 serve as polar residues necessary for the acid-based catalytic reaction of chitin synthase. PMID- 9990312 TI - UDP-glucuronosyltransferase UGT1A7 induced in rat small intestinal mucosa by oral administration of 2-naphthoflavone. AB - In the rat intestine, UDP-glucuronosyltransferase (UGT) isoforms were highly induced by oral administration of 2-naphthoflavone, as shown by intestinal UGT activity toward 1-naphthol (1-NA). The greatest increase in UGT activity occurred in the duodenum. Using UGT1A6 cDNA as a probe, we obtained three types of clones corresponding to UGT1A2, UGT1A6 and UGT1A7, in a ratio of 1:1:8, from a cDNA library constructed from the 2-naphthoflavone-treated rat intestine. The induction of each isoform was evaluated by means of Northern blotting with isoform-specific probes. The mRNAs of UGT1A6 (glucuronizing various phenolic xenobiotics) and the mRNAs of UGT1A7 (glucuronizing the ultimate carcinogenic metabolite of benzo(a)pyrene) were expressed constitutively and were highly induced in the duodenum and proximal jejunum. S1 mapping showed that induction of the isoforms of the UGT1 family was more pronounced in the liver than in the small intestine and that UGT1A7 was the major UGT1 isoform in the small intestine of vehicle-treated rats and in that of 2-naphthoflavone-treated rats. These results indicate that, in rats, UGT1A7 is expressed constitutively and is particularly inducible in the small intestine. In the light of these results, we believe that the UGT1A7 isoform would play an important role in glucuronidation in the small intestinal mucosa of rats. PMID- 9990313 TI - A control analysis exploration of the role of ATP utilisation in glycolytic-flux control and glycolytic-metabolite-concentration regulation. AB - A theoretical metabolic-control-analysis approach has been used to study aspects of glycolytic-flux control and carbon-metabolite regulation, particularly the role of ATP demand (ATPase), in order to determine what general features of the regulation of energy metabolism would be consistent with good carbon-metabolite homeostasis in the face of large changes in carbon flux. On the basis of a semi quantitative control-analysis model, incorporating estimates of substrate, product and effector actions on the enzymes, the experimentally observed characteristics of glycolytic-flux changes prove to impose constraints on the feasible ranges of these estimates. This leads to the identification of several features of energy metabolism, each of which is necessary but not sufficient to explain the observations; although most of these have been advocated previously (such as AMP activation of phosphofructokinase (PFK), ADP inhibition of ATPase and the role of energy charge or ATP/ADP ratio), our analysis allows their relative importance to be assessed. In the model, the distribution of flux control depends primarily on ADP inhibition of ATPase, and on the activation of PFK by AMP; increase in ADP inhibition of ATPase increases the control on PFK; increase in AMP activation of PFK increases control on ATPase. PFK exerts greater flux control than does ATPase over approximately 50% of the ranges (parameter space) studied, but its control is sufficiently high to achieve sizeable flux increases over less than 20% of the space. Furthermore, control by alteration in PFK activity is shown to result in poor glycolytic metabolite homeostasis over the entire parameter space studied. However, over a large proportion of the parameter space, control by activation of ATPase can lead to large flux changes, i.e. high flux control, coupled with excellent glycolytic-metabolite homeostasis, similar to that observed in working muscle. As well as altering the relative degrees of flux control invested in PFK and ATPase, ADP inhibition of ATPase and AMP activation of PFK have pronounced effects on the homeostatic properties of the system. Stronger ADP inhibition of ATPase results in improved homeostasis of glycolytic metabolites, ATP and ADP in response to PFK activation, whereas stronger activation of PFK by AMP improves the homeostasis of these three quantities in response to ATPase activation. The results are further evidence of the potential for physiological ATP demand to exert control over glycolytic flux, but additionally show that the known effector interactions, in addition to their previously known role in ATP regulation, could contribute to the remarkable homeostasis of glycolytic-metabolite levels observed in vivo. They further indicate that quantitative characterisation of likely domains of behaviour of metabolic systems can be achieved by an algebraic analysis that is not highly dependent on a full and precise knowledge of the molecular details of the kinetic/regulatory properties of the enzymes, but that still allows an assessment of whether hypotheses regarding the system are feasible and sufficient to account for the observations. PMID- 9990314 TI - Two gamma-interferon-activation sites (GAS) on the promoter of the human intercellular adhesion molecule (ICAM-1) gene are required for induction of transcription by IFN-gamma. AB - We describe the molecular features of the interferon (IFN)-gamma-mediated transcription of the human intercellular adhesion molecule (ICAM-1) gene. We identified putative IFN-gamma-activated sites (GAS) distributed throughout a large segment of the ICAM-1 promoter (4.0 kb region). Using computer-assisted search, these sequences were similar to potential IFN-gamma responsive elements that have a core sequence 5'-TTNCNNNAA-3'. In this report we show that in the ICAM-1 promoter a GAS site is located at -115 from the translation initiation site, and binds with strong affinity to IFN-gamma-activated Signal Transducers and Activators of Transcription (STAT1) homodimers. The same sequence is responsible for the IFN-gamma-mediated transcription of the ICAM-1 gene. Moreover, we present evidence that a more distal GAS element that maps at -2787 from the translation initiation site, binds IFN-gamma-activated STAT1 dimers with lower affinity. Multimeric copies of such GAS sequence inserted into a tkCAT minimal promoter can drive transcription, demonstrating that the -2787 bp GAS element has an independent functional activity upon binding of IFN-gamma activated STAT1 proteins as documented by in vitro binding assays. Furthermore, using recombinant ICAM-CAT mutants, we show that, in vivo, the -2787 GAS, but not a mutagenized -2787 GAS site, when coupled to the more proximal -115 GAS element, has an additive effect in enhancing the IFN-gamma-mediated transcription of ICAM 1 promoter. Nevertheless, using a recombinant construct bearing the wild type 2787 GAS element and a mutagenized -115 GAS element, we could not detect any transcription after transfection of U937 recipient cells, suggesting that the 2787 bp GAS element is not sufficient as such for gene activation, but can cooperate with its cognate proximal sequence to give full function to the ICAM-1 promoter during the IFN-gamma response. Taken together these data provide evidence that two GAS sites are required for the full potential activity in the mechanism of ICAM-1 gene activation by IFN-gamma. PMID- 9990315 TI - Thrombopoietin potentiates the protein-kinase-C-mediated activation of mitogen activated protein kinase/ERK kinases and extracellular signal-regulated kinases in human platelets. AB - The thrombopoietin (TPO) receptor is expressed in the megakaryocytic lineage from late progenitors to platelets. We investigated the effect of TPO on the extracellular signal-regulated kinase (ERK) activation pathway in human platelets. TPO by itself did not activate ERK1, ERK2 and protein kinase C (PKC), whereas TPO directly enhanced the PKC-dependent activation of ERKs induced by other agonists including thrombin and phorbol esters, without affecting the PKC activation by those agonists. TPO did not activate the mitogen-activated protein kinase/ERK kinases, MEK1 and MEK2, but activated Raf-1 and directly augmented the PKC-mediated MEK activation, suggesting that TPO primarily potentiates the ERK pathway through regulating MEKs or upstream steps of MEKs including Raf-1. The MEK inhibitor PD098059 failed to affect not only thrombin-induced or phorbol ester-induced aggregation, but also potentiation of aggregation by TPO, denying the primary involvement of ERKs and MEKs in those events. ERKs and MEKs were located mainly in the detergent-soluble/non-cytoskeletal fractions. ERKs but not MEKs were relocated to the cytoskeleton following platelet aggregation and actin polymerization. These data indicate that TPO synergizes with other agonists in the ERK activation pathway of platelets and that this synergy might affect functions of the cytoskeleton possibly regulated by ERKs. PMID- 9990316 TI - Competition and cooperation amongst yeast elongation factors. AB - Elongation factor 3 (EF-3) is an essential requirement for translation in fungi. We previously reported activation of EF-3-ATPase by yeast ribosomes. EF-3 interacts with both ribosomal subunits and shows high affinity for 60S subparticles. Translational inhibitors alpha-sarcin, ricin and auto-immune antibodies to GTPase-activation center inhibit binding of EF-2 but not of EF-3 to yeast ribosomes. EF-2 competes with EF-3 for the ribosomal binding sites and inhibits EF-3-ATPase activity. Neomycin relieves the inhibitory effect of EF-2 on EF-3 function. The apparent competition between EF-2 and EF-3 may represent binding of these two proteins to specific conformational states of the ribosome. EF-3 stimulates ternary complex binding to yeast ribosomes. Neither the binding of EF-3 to ribosomes, nor the ribosome-dependent EF-3-ATPase activity are influenced by EF-1 alpha. Three lines of experimental evidence suggest a direct interaction between EF-1 alpha and EF-3. A polyclonal antibody to EF-3 immunoprecipitates EF-1 alpha along with EF-3. EF-1 alpha co-migrates with GST-EF 3 on glutathione-Sepharose columns. ELISA tests demonstrate an interference of EF 3/anti-EF-3 interaction by EF-1 alpha but not by EF-2. These results strongly suggest that the stimulatory effect of EF-3 on the ternary complex binding to yeast ribosomes involves a direct interaction between EF-1 alpha and EF-3. PMID- 9990317 TI - A chicken homolog of mammalian interleukin-1 beta: cDNA cloning and purification of active recombinant protein. AB - Upon induction with lipopolysaccharide (LPS) the chicken macrophage cell line HD 11 secretes an activity that stimulates the synthesis of a CXC chemokine in the chicken fibroblast cell line CEC-32. We used a cDNA expression cloning strategy in COS cells to characterize this activity. The isolated cDNA clone codes for a polypeptide of 267 amino acids which lacks a hydrophobic N-terminal domain that could serve as secretory signal. Sequence homology and structural features indicate that this protein is the chicken homolog of mammalian interleukin-1 beta (ChIL-1 beta). Northern blot analysis showed that ChIL-1 beta RNA is quickly induced in blood monocyte-derived macrophages reaching maximal levels within one hour after onset of LPS treatment. To test for biological activity of putative mature ChIL-1 beta, a cDNA fragment comprising amino acids 106 to 267 of the open reading frame was expressed in Escherichia coli so that the resulting polypeptide carried a histidine tag at its N-terminus for easy purification by nickel chelate affinity chromatography. Purified His-ChIL-1 beta potently induced CXC chemokine RNA synthesis in CEC-32 cells. When injected intravenously into adult chickens, it quickly induced a transient increase in serum corticosterone levels. PMID- 9990318 TI - FhuF, an iron-regulated protein of Escherichia coli with a new type of [2Fe-2S] center. AB - We previously used fhuF as a sensitive reporter gene of the iron status of Escherichia coli. In this report, the fhuF gene was identified as open reading frame f262b at 99.2 min on the genome sequence map of E. coli K-12. The FhuF protein was labeled with a His-tag and then purified to electrophoretic homogeneity. Based on sulfur determinations and Mossbauer and EPR spectroscopy, FhuF was identified as a [2Fe-2S] protein. The g values (gx = 1.886, gy = 1.961, gz = 1.994) and some of the Mossbauer parameters of FhuF obtained [oxidized protein as isolated: delta EQ,4.2K = 0.474 mm s-1; Fe3+ (reduced protein): delta EQ = 0.978 mm s-1] are not typical of common [2Fe-2S] proteins and indicate that FhuF has unusual structural properties. The primary sequence of FhuF does not show any sequence similarities to known [2Fe-2S] proteins. By site-directed mutagenesis, each of the six cysteines of FhuF was replaced by serine. EPR of the six reduced mutant proteins revealed that the terminal cysteine residues 244, 245, 256, and 259 form the [2Fe-2S]Cys4 cluster. Mutants having the Cys-to-Ser replacement at positions 244, 245, 256, or 259 did not complement a fhuF mutant. The motif Cys-Cys-Xaa10-Cys-Xaa2-Cys in FhuF differs considerably from the motif Cys-Xaa2-Cys-Xaa9-15-Cys-Xaa2-Cys found in other [2Fe-2S] proteins. The unusual Cys-Cys terminal group of the cluster may explain the atypical EPR and Mossbauer spectroscopic properties of the FhuF protein; possibly the tetrahedral symmetry at the ferric ion site is distorted. The phenotype of fhuF mutants and the structural features of the FhuF protein suggest that FhuF is involved in the reduction of ferric iron in cytoplasmic ferrioxamine B. PMID- 9990319 TI - An apyrase from Mimosa pudica contains N5,N10-methenyl tetrahydrofolate and is stimulated by light. AB - An apyrase (NTP/NDPase) implicated in the response of Mimosa pudica to stimuli, such as touch, has been cloned, sequenced and expressed in Escherichia coli. While purifying and characterizing this enzyme, it was observed that a chromophore is associated with it, having absorption in the ultraviolet-A/blue region of the spectrum. The absorbance maximum of the chromophore, purified from the enzyme complex by gel filtration and HPLC, is around 350 nm. The chromophore has been identified as N5,N10-methenyl tetrahydrofolate (MTHF) by comparing the excitation and emission spectra of synthetic MTHF and the isolated cofactor, and by reconstitution of the enzyme complex with synthetic MTHF. Upon excitation with light (350 nm), an increase of apyrase activity was observed in the purified or reconstituted holoenzyme but not in the apoenzyme. The wavelength dependence of the light stimulation matched well with the fluorescence excitation spectra of the cofactor, MTHF. Possible implications of the results for signal transduction in M. pudica have been discussed. PMID- 9990320 TI - The mammalian small heat-shock protein Hsp20 forms dimers and is a poor chaperone. AB - Hsp20 is one of the newly described members of the mammalian small heat-shock protein (sHsp) family. It occurs most abundantly in skeletal muscle and heart. We isolated clones for Hsp20 from a rat heart cDNA library, and expressed the protein in Escherichia coli to characterize this little known sHsp. Recombinant Hsp20 displayed similar far-ultraviolet circular dichroism spectra as the most closely related sHsp, alpha B-crystallin, but was less heat stable, denaturing upon heating to 50 degrees C. While other mammalian recombinant sHsps form large multimeric complexes, Hsp20 occurs in two complex sizes, 43-kDa dimers and 470 kDa multimers. The ratio between the two forms depends on protein concentration. Moreover, Hsp20 has a much lower chaperone-like activity than alpha B-crystallin, as indicated by its relatively poor capacity to diminish the reduction-induced aggregation of insulin B chains. Hsp20 is considerably shorter at the C-terminus and less polar than other sHsps, but 1H-NMR spectroscopy reveals that the last 10 residues are flexible, as in the other sHsps. Our findings suggest that Hsp20 is a special member of the sHsp family in being less heat stable and tending to form dimers. These properties, together with the shorter and less polar C-terminal extension, may contribute to the less effective chaperone-like activity. PMID- 9990321 TI - Transferrins. Hen ovo-transferrin, interaction with bicarbonate and iron uptake. AB - Fe(III) uptake by the iron-delivery and iron-scavenging protein, hen ovotransferrin has been investigated in vitro between pH 6.5 and 9. In the absence of any ferric chelate, apo-ovotransferrin loses two protons with K1a = 50 +/- 1 nM and K2a = 4.0 +/- 0.1 nM. These acid-base equilibria are independent of the interaction of the protein with bicarbonate. The interaction with bicarbonate occurs with two different affinity constants, KC = 9.95 +/- 0.15 mM and KN = 110 +/- 10 mM. FeNAc3 exchanges its Fe(III) with the C-site of the protein in interaction with bicarbonate, direct rate constants k1 = 650 +/- 25 M-1 s-1, reverse rate constant k-1 = (6.0 +/- 0.1) x 10(3) M-1 s-1 and equilibrium constant K1 = 0.11 +/- 0.01. This iron-protein intermediate loses then a single proton, K3a = 3.50 +/- 0.35 nM, and undergoes a first change in conformation followed by a two or three proton loss, first order rate constant k2 = 0.30 +/- 0.01 s-1. This induces a new modification in conformation followed by the loss of one or two protons, first order rate constant k3 = (1.50 +/- 0.05) x 10(-2) s-1. These modifications in the monoferric protein conformation are essential for iron uptake by the N-site of the protein. In the last step, the monoferric and diferric proteins attain their final state of equilibrium in about 15,000 s. The overall mechanism of iron uptake by ovotransferrin is similar but not identical to those of serum transferrin and lactoferrin. The rates involved are, however, closer to lactoferrin than serum transferrin, whereas the affinities for Fe(III) are lower than those of serum transferrin and lactoferrin. Does this imply that the metabolic function transferrins is more related to kinetics than to thermodynamics? PMID- 9990322 TI - DNA synthesis exhibited by the reverse transcriptase of mouse mammary tumor virus: processivity and fidelity of misinsertion and mispair extension. AB - We have recently expressed in bacteria an enzymatically active reverse transcriptase (RT) of mouse mammary tumor virus (MMTV), a mammalian retrovirus with a typical B-type morphology [Taube, R., Loya, S., Avidan, O., Perach, M. & Hizi, A. (1998) Biochemical J. 329, 579-587]. The purified recombinant protein was shown to possess the catalytic activities characteristic of retroviral reverse transcriptases. In the present study, we have analyzed two basic parameters characteristic of the DNA polymerase activity of the novel MMTV RT, namely the processivity and the fidelity of DNA synthesis. Two features related to fidelity were studied, the capacity to misinsert wrong nucleotides at the 3' end of the nascent DNA strand and the ability to extend 3' mispairs. The studied properties of MMTV RT were compared with those of the RT purified from virions of avian myeloblastosis virus (AMV), since AMV RT shows a relatively high sequence similarity to MMTV RT. MMTV RT shows a relative processivity of DNA synthesis which is as high as the reference AMV RT. Regarding fidelity of DNA synthesis, MMTV RT shows a fidelity of misinsertion lower than that of AMV RT, whereas its capacity to elongate mispaired DNA is lower than that of AMV RT indicating a somewhat higher fidelity. These fidelity properties are discussed also in the context of the RTs of lentiviruses, especially those of HIV, which were reported to exhibit an exceptionally low fidelity of DNA synthesis. It is clear that MMTV RT has a fidelity higher than that of lentiviral RTs. PMID- 9990323 TI - Differential redox and electron-transfer properties of purified yeast, plant and human NADPH-cytochrome P-450 reductases highly modulate cytochrome P-450 activities. AB - Saccharomyces, human and two Arabidopsis (ATR1 and ATR2) NADPH-P-450 reductases were expressed in yeast, purified to homogeneity and used to raise antibodies. Among the P-450-reductases, ATR2 contrasted by its very low FMN affinity and required a thiol-reducing agent for efficient cofactor binding to the FMN depleted enzyme. Analysis of reductase kinetic properties using artificial acceptors and different salt conditions suggested marked differences between reductases in their FAD and FMN environments and confirmed the unusual properties of the ATR2 FMN-binding domain. Courses of flavin reductions by NADPH were analysed by rapid kinetic studies. The human enzyme was characterized by a FAD reduction rate sixfold to tenfold slower than values for the three other reductases. Following the fast phase of reduction, expected accumulation of flavin semiquinone was observed for the human and ATR1 but not for ATR2 and the yeast reductases. Consistently, redox potential for the FMN semiquinone/reduced couple in the yeast enzyme was found to be more positive than the value for the FMN oxidized/semiquinone couple. This situation was reminiscent of similar inversion observed in bacterial P-450 BM3 reductase. Affinities of reductases for rabbit P-450 2B4 and supported monooxygenase activities in reconstituted systems highly depended on the reductase source. The human enzyme exhibited the highest affinity but supported the lowest kcat whereas the yeast reductase gave the best kcat but with the lowest affinity. ATR1 exhibited both high affinity and efficiency. No simple relation was found between reductase activities with artificial and natural (P-450) acceptors. Thus marked differences in kinetic and redox parameters between reductases dramatically affect their respective abilities to to support P-450 functions. PMID- 9990324 TI - Thermotoga maritima maltosyltransferase, a novel type of maltodextrin glycosyltransferase acting on starch and malto-oligosaccharides. AB - A novel enzyme acting on starch and malto-oligosaccharides was identified and characterised. The non-hydrolytic enzyme, designated maltosyltransferase (MTase), of the hyperthermophilic bacterium Thermotoga maritima MSB8 disproportionates malto-oligosaccharides via glycosyl transfer reactions. The enzyme has a unique transfer specificity strictly confined to the transfer of maltosyl units. Incubation of MTase with starch or its constituents. i.e. amylose and amylopectin, led to the formation of a set of multiples of maltose (i.e. maltose, maltotetraose, maltohexaose etc.). Malto-oligosaccharides with a degree of polymerization (DP) X were disproportionated to products with a DP of X +/- 2n (with X > or = 3 and n = 0,1,2,...). Maximum activity in a 10-min assay was recorded at pH 6.5 and 85-90 degrees C. The enzyme displayed extraordinary resistance to thermal inactivation. For example, at 90, 85, and 70 degrees C (pH 6.5, 0.34 mg ml-1 protein), MTase half-lives of about 2.5 h, 17 h, and 21 days, respectively, were recorded. The gene for MTase, designated mmtA, was isolated from a gene library of T. maritima strain MSB8. Analysis of the MTase primary structure as deduced from the nucleotide sequence of mmtA revealed that the enzyme is not closely related to known protein sequences. However, low-level local similarity between MTase and the alpha-amylase enzyme family (glycosyl hydrolase family 13) was detected, including conserved acidic residues essential for catalysis. Therefore, MTase should be assigned to this family. Based on detailed sequence analyses and comparison with amylolytic enzymes of known crystal structure we propose that MTase contains a (beta/alpha)8-fold as the core supersecondary structure which is typical for the alpha-amylase family. On the other hand, MTase is unique in that it lacks several residues highly conserved throughout this family. Also, MTase possesses an extraordinarily large domain B (a domain typical for the alpha-amylase family, inserted between beta-strand 3 and alpha-helix 3 of the (beta/alpha)8-barrel fold). PMID- 9990325 TI - The StrQ protein encoded in the gene cluster for 5'-hydroxystreptomycin of Streptomyces glaucescens GLA.0 is a alpha-D-glucose-1-phosphate cytidylyltransferase (CDP-D-glucose synthase). AB - The gene strQ was identified as the last gene of a putative transcription unit, strB1FGHPQ, located in the gene cluster for the production of 5'-hydroxy streptomycin (OH-Sm) in Streptomyces glaucescens GLA.0. [In contrast, the corresponding operon in the str/sts-gene cluster of the Sm-producer Streptomyces griseus, strB1FGHIK, differs in the two distal genes; Mansouri, K. & Piepersberg, W. (1991) Mol. Gen. Genet. 228, 459-469]. The deduced StrQ protein exhibited similarities to members of the enzyme family of hexose-1-phosphate nucleotidylyltransferases (NDP-hexose synthases or pyrophosphorylases), with the strongest similarity to the subfamily of alpha-D-glucose-1-phosphate cytidylyltransferases (CDP-D-glucose synthases). The StrQ protein was heterologously expressed in Escherichia coli. The purified protein revealed an enzyme activity of that of a CDP-D-glucose synthase and a substrate specificity restricted to CTP and alpha-D-glucose 1-phosphate. The K(m) and Vmax values determined for CTP are 44 microM and 920 microM and for alpha-D-glucose 1 phosphate 195 microM and 1.06 mM, respectively. The CDP-D-glucose synthase activity was also detected in cells of S. glaucescens under the conditions of antibiotic production, but was absent from cells of the streptomycin producer S. griseus N2-3-11. Also, the genomes of several strains of S. griseus did not seem to possess strQ-related genes. In contrast, hybridisation experiments indicated that genes homologous to strQ were probably present in various other actinomycetes producing aminoglycosides. A possible function of the StrQ protein in the OH-Sm biosynthetic pathway of GLA.0 is discussed. PMID- 9990326 TI - Production of key molecules by ocular neutrophils early after herpetic infection of the cornea. AB - Herpes simplex virus infection of the eye can result in a blinding inflammatory lesion that is a T cell mediated immunopathological reaction. A prominent early event following HSV infection is neutrophil invasion of the corneal stroma. These cells may be involved in viral clearance and may influence the nature of the anti HSV T cell response which subsequently occurs. This article measures the expression of some key molecules which could participate in viral clearance and immune modulation. Using RT-PCR and in-situ hybridization, both corneal and peritoneal neutrophils were shown to be sources of iNOS and TNF alpha molecules which likely contribute to antiviral activity. Neutrophils also produce the cytokine IL-12, a key molecule which modulates the CD4+ T cell response to a type which mediates immunopathology. The present results indicate that neutrophils play an important role in the pathogenesis of herpetic ocular lesions. PMID- 9990327 TI - An improved method for examining the corneal endothelium during graft rejection in the rat. AB - An improved method of removing rat corneal endothelial sheets for study of endothelial pathology is described. The method was validated by examining morphological changes and changes in expression of major histocompatibility complex (MHC) and intercellular adhesion molecule (ICAM)-1 on endothelium undergoing immunological rejection. PVG strain rats received LEW strain corneal transplants or corneal isografts. Just prior to and during graft rejection, animals were killed, together with a group of untreated animals. The corneal stroma was injected with dispase or PBS, the cornea was carefully removed, fixed in acetone and the endothelium was gently peeled off and flattened on to a glass slide. Morphological changes, together with MHC class I, class II and ICAM-1 expression were visualised by immuno-histochemical staining and quantified by image analysis. Near complete endothelial sheets were obtained by this method. Because of the thin cell layer, there was minimal background staining, permitting rejection-associated changes to be clearly seen. MHC class I expression on normal endothelium was low and not significantly increased on endothelial cells of allografts at the time of rejection compared with controls (P = 0.1). MHC class II and ICAM-1 were induced de novo, expression being significantly higher on allografts than on isografts (P = 0.004 for MHC class II and P = 0.01 for ICAM 1). MHC class I and II and ICAM-1 were expressed on many infiltrating cells. Thus, this preparation method permits clear identification of the distribution and morphology of infiltrating cells and other mediators of the immune response in the entire donor endothelium. It confirms that MHC class I expression is low during rejection, while MHC class II and ICAM-I are induced de novo and strongly expressed. PMID- 9990328 TI - The effect of continuous light on refractive error and the ocular components of the rat. AB - Phototoxic induced degeneration of the rat retina is a well-documented phenomenon resulting in losses of photoreceptors and their cell bodies, and an overall retinal thinning. This process may serve as a test of the hypothesis that the retinoscopic reflex originates from the inner limiting membrane of the retina. Retinal thinning should produce myopia in the absence of any other ocular component changes in a stable, mature eye if the inner limiting membrane model is correct. Phototoxic retinal degeneration was induced in 10 albino rats by exposure to 19 days of continuous light (1,800 cd m-2). Another 10 albino rats exposed to 12-hr on/12-hr off cycled light served as controls. Before and after the exposure to constant light, measures were made of refractive state by cycloplegic retinoscopy, corneal curvature and lens curvature by Purkinje image photography, and axial length of the globe by A-scan ultrasonography. Comparing pre- to post-exposure values, phototoxic degeneration resulted in a mean (+/- S.D.) myopic shift of -5.10 +/- 2.12 D (P < 0.002). The corneal curvature also steepened significantly (0.17 +/- 0.11 mm, equivalent to -6.0 D; P < 0.004), while the posterior curvature of the crystalline lens flattened by 0.21 +/- 0.22 equivalent mm (P < 0.027), and the axial length shortened by 0.11 +/- 0.11 equivalent mm (all tests Wilcoxon signed-rank; P < 0.025). Phototoxic rats underwent a mean retinal thinning of 49.6 mu compared to controls (Kruskal-Wallis test; P < 0.0008). No refractive or ocular parameters changed significantly in the controls. Phototoxic degeneration in the rat has optical consequences beyond simple retinal thinning. The size of the eye and the curvature of refractive surfaces can be altered in a mature eye well after the completion of development. The multiple changes which occur prevent phototoxic retinal thinning from serving as a test of the inner limiting membrane model for retinoscopic reflections. PMID- 9990329 TI - Increase in interphotoreceptor matrix gelatinase A (MMP-2) associated with age related macular degeneration. AB - Matrix metalloproteinases have increasingly been shown to be associated with diseases involving neovascularization and/or abnormal cellular migration or proliferation. A number of diseases of this type affect the retina. In this study, the activity of gelatinase A (MMP-2), the most abundant matrix metalloproteinase in IPM (interphoto receptor matrix) and vitreous, was measured with respect to age in normal human donor eyes and compared to donors with age related macular degeneration. IPM and vitreous were obtained from a total of 88 human donors. Samples for electrophoresis were normalized for protein content and subjected to quantitative gelatin zymography. The zymograms were scanned and then digitized and quantitated using the NIH 'Image' program. There was not a statistically significant change in the level of gelatinase A in IPM or vitreous as a function of age, although a slight downward trend was found in the total gelatinase A activity within the normal population. Likewise, when comparing normal and age-related macular degeneration donors, there was not a significant difference in the gelatinase A level in vitreous or in retina-associated IPM. However, the level of gelatinase A was nearly doubled specifically in retinal pigment epithelium-associated IPM from eyes with age-related macular degeneration [0.99 +/- 0.09 U mg-1 (56) vs 1.71 +/- 0.28 U mg-1 (14) (mean +/- S.E.M. (number), P < 0.0021; 1 unit = 1.0 ng gelatin cleaved h-1). Gelatinase A may be associated with the changes that occur in age-related macular degeneration, especially the neovascularization which accompanies the exudative ('wet') form of the disease. PMID- 9990330 TI - The effect of catalase amplification on immortal lens epithelial cell lines. AB - Utilizing a human beta-actin promoter, a catalase cDNA expression vector was constructed. This construct was used to transfect two immortal cell lines, mouse alpha TN4-1 and rabbit N/N 1003A. The catalase activity was increased about 3.4 fold in the alpha TN4-1 cells and 38 fold in the N/N 1003A cells. Some changes in other enzyme activities were also observed as a result of the transfections. Surprisingly, the ability to degrade H2O2 in the extracellular environment of the cells did not markedly change as a result of the catalase amplification. However, the ability to resist H2O2 stress was dramatically altered. Non-protein thiol (NP SH) levels, choline uptake and glyceraldehyde phosphate dehydrogenase (GPD) activity were all markedly decreased in the non-transfected cells when they were subjected to 300 microM H2O2. However, in both transfected cell lines, these parameters remained in the normal range during H2O2 stress. The results obtained upon observing aspects of DNA metabolism were more complicated. While on H2O2 stress, non-transfected cell lines showed a marked decrease in thymidine incorporation, only the transfected alpha TN4-1 line remained in the normal range. Thymidine incorporation in transfected rabbit N/N 1003A cells was decreased compared to normal cells. In contrast, studies on single strand DNA breaks indicated that transfected rabbit cells had little damage compared to the significant DNA damage observed in the normal cells. The normal N/N 1003A cells were also much more susceptible to H2O2 induced damage than normal alpha TN4-1 cells, suggesting that the high GSH peroxidase activity observed in the rabbit cells may be detrimental since the low glutathione reductase activity in such cells results in an accelerated depletion of glutathione. The overall results suggest that augmenting lens catalase may prevent cataract development caused by H2O2 stress. PMID- 9990331 TI - Studies of the denaturation patterns of bovine alpha-crystallin using an ionic denaturant, guanidine hydrochloride and a non-ionic denaturant, urea. AB - The effects of non-ionic and ionic denaturation and denaturation/renaturation on the native structure of alpha-crystallin at room temperature were examined. Native alpha-crystallin, at concentrations above and below the previously reported critical micelle concentration (CMC) range, was denatured by varying concentrations of urea and guanidine hydrochloride. The resulting denatured samples were examined by gel filtration fast performance liquid chromatography (FPLC), circular dichroism spectropolarimetry (CD), and transmission electron microscopy. Elution peak samples from gel filtration chromatography with sufficiently high concentrations were examined for subunit composition by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). The studies presented herein demonstrate that the denaturation and renaturation of alpha crystallin via non-ionic urea denaturation results in different renaturation species, depending upon the initial concentration of alpha-crystallin which is denatured and the concentration of urea, including certain species which, by gel filtration FPLC, have an apparent molecular weight greater than the native 800 kD aggregate. Transmission electron microscopy has also demonstrated the existence of a high molecular weight aggregate form for denatured samples. Ionic dissociation, in contrast, proceeds much in the same manner above and below the CMC range, the major difference occurring at 2 M guanidine hydrochloride. alpha B crystallin is preferentially removed from the native alpha-crystallin aggregate upon treatment with 2 M guanidine hydrochloride indicating, once again, differences between the two subunits. Above and below the CMC range, dissociation with guanidine hydrochloride appears to plateau after 4 M guanidine hydrochloride as indicated by the presence of two apparent homotetrameric species and no further dissociation of these species with increasing guanidine hydrochloride concentrations. CD demonstrates that some secondary structure, which is lost with lower concentrations of alpha-crystallin, is still present when concentrations of alpha-crystallin, well above the critical micelle concentration range, are treated with high concentrations of urea at room temperature. In contrast, concentrations both above and below the CMC range demonstrate a significant loss of secondary structure upon treatment with 2 M guanidine hydrochloride. Finally, ionic denaturation and subsequent renaturation results in the formation of a species which is functionally incapable of protecting gamma-crystallin from heat induced aggregation. PMID- 9990332 TI - The exposed ocular surface and its relationship to spontaneous eyeblink rate in elderly caucasians. AB - The purpose of this study was to assess spontaneous eyeblink activity in the primary eye position, and its relationship to the exposed ocular surface area in elderly individuals without significant ocular surface disease. Spontaneous eyeblink frequency (SEBF) was assessed for a group of Caucasians aged 61 to 81 years, by videography in silence over a 5 min period; inter-blink interval (IBI), the maximum inter-blink interval (mIBI) and the modal eyeblink frequency (mEBF) were derived from video recordings. The ocular surface area was calculated from video-planimetry using different formulae. The average palpebral aperture was 8.3 +/- 2.3 mm (n = 45, +/- S.D.), resulting in an average exposed area of 1.13-2.13 cm2 depending on the formula used; the preferred estimate was 1.25 cm2. A highly significant relationship (P < 0.001, r2 = 0.835) was found between time-averaged palpebral aperture (p) and exposed ocular surface (A = 0.244p-0.763). An average SEBF of 11.9 blinks min-1 was measured (range 0.8-43.6). No correlation (P > 0.35, r2 < or = 0.01) was found between SEBF, IBI, mIBI, or mEBF and the palpebral aperture or the exposed surface area, regardless of the formulae used. The exposed ocular surface area per se does not appear to be an important determinant of spontaneous eyeblink activity in elderly Caucasians. PMID- 9990333 TI - Expression of Fas-Fas ligand antigens and apoptotic marker APO2.7 by the human conjunctival epithelium. Positive correlation with class II HLA DR expression in inflammatory ocular surface disorders. AB - Fas antigen (CD95) is a membrane receptor that plays a major role in induction of apoptosis. In surface conjunctival epithelial cells the expressions of Fas, Fas ligand, the apoptotic marker APO2.7 and of HLA DR class II antigen, a membrane marker known to be expressed in inflammatory conditions were investigated. Impression cytology specimens were collected in 65 patients: 20 normal ones, 15 contact lens wearers, 20 receiving chronic topical antiglaucoma treatment and 10 with nonspecific chronic conjunctivitis. Cells were processed for flow cytometry, using monoclonal antibodies to Fas, Fas ligand, APO2.7, HLA DR antigens and a negative isotypic control. Percentages of positive cells were recorded and levels of fluorescence quantified using fluorescent beads at standardized fluorescence intensities. In addition, a human conjunctival cell line was incubated with anti Fas stimulating antibodies in order to test Fas-induced apoptosis in vitro. Fas was found in all specimens in most of the conjunctival cells, but quantitation of levels of fluorescence showed a significantly higher expression in pathologic eyes than in normal ones. Fas ligand and APO2.7 were variably expressed by conjunctival cells, but in a significantly higher percentage of cells in pathological eyes than in normal ones. In these eyes a strong expression of HLA DR was also observed, whereas normal eyes showed lowest levels. Highly significant correlations were found between Fas, Fas ligand, APO2.7 and HLA DR levels. Anti-Fas antibodies in vitro induced strong apoptosis in epithelial cells as confirmed by APO2.7 expression and DAPI staining. This study confirms that conjunctival epithelial cells normally express Fas antigen, and more inconstantly its ligand, as do corneal ones or keratinocytes. Fluorescence quantitation by flow cytometry showed much higher expression in inflammatory eyes than in normal ones, and demonstrated a strong correlation between apoptotic and inflammatory pathways in the ocular surface. PMID- 9990334 TI - Localization of Six4/AREC3 in the developing mouse retina; implications in mammalian retinal development. AB - The Six4/AREC3 gene was originally isolated as a regulatory factor which bound to the positive regulatory region of the Na, K-ATPase alpha 1 subunit. It is a murine homologue of the Drosophila sine oculis (so) gene, which is essential for the development of the entire insect visual system. In this study, we attempted to determine the localization of the Six4/AREC3 gene product in the developing mouse retina in order to examine its role in retinal cell differentiation. Immunohistochemistry with anti-SIX4/AREC3 and anti-Na, K-ATPase alpha 1 subunit antisera was performed on developing mouse retinas, and immunoblotting analysis with anti-SIX4/AREC3 was also performed. The localization of Six4-like immunoreactivity (Six4-LI) showed a temporally regulated pattern: During embryonic development, Six4-LI was found in the nuclei of cells located at the inner neuroblastic layer of the retina as early as on ED12, nearly corresponding to the onset of retinal cell differentiation. In the PD1 retina, Six4-LI was observed in the nuclei of the ganglion cells, and increased its intensity until PD4, and thereafter kept its intensity until PD7 when Six4-LI was often found in the cytoplasm. On PD4, the presumptive amacrine cells found in the inner portion of the inner nuclear layer appeared to be immunostained in their nuclei. On PD7, the presumptive bipolar cells located in the outer portion were immunostained in the nuclei. After that, Six4-LI gradually decreased, and in the mature retina no detectable Six4-LI was observed in the nuclei. This pattern of Six4-LI localization during retinal development seemed to correlate with retinal cell differentiation, but did not correlate with the distribution pattern of Na, K ATPase alpha 1 subunit protein-like immunoreactivity. These results suggest that the Six4 gene may play a role in the differentiation of neural retinal cells during mouse retinal development, rather than regulating the expression of the Na, K-ATPase alpha 1 subunit gene. PMID- 9990335 TI - Biochemical analysis of ocular surface mucin abnormalities in dry eye: the canine model. AB - This study examines the canine model of keratoconjunctivitis sicca (KCS, 'dry eye') in order to establish the biochemical basis of altered ocular mucin secretion in this condition. It follows a previous examination of ocular mucins in the normal dog. Mucus was collected by suction from the ocular surface of dogs with KCS, and dispersed in guanidine hydrochloride containing a cocktail of protease inhibitors. Caesium chloride density gradient centrifugation was used to separate floating 'rafts' of cell membranes from gradients containing secreted mucins. Gradient fractions were collected into pools on the basis of differential staining by Periodic Acid Schiff, Wheat Germ Agglutinin, and antibodies to MUC5AC peptide. High molecular weight glycoproteins were purified from the pooled material by gel filtration chromatography. Membrane-associated glycoproteins were also derived from the membrane rafts using octyl glucoside extraction and/or reduction and alkylation. Secreted mucins and membrane extracts from KCS samples were compared to equivalent material obtained from normal eyes. Density gradient staining profiles for normal and KCS mucus were similar over the buoyant density range typical for secreted mucins, enabling the collection of identical pools of gradient fractions for direct comparison. The following differences were observed in KCS secreted mucins compared to normal samples: an increase in the proportion of mucin with low buoyant density; a decrease in mannose content detected with Concanavalin A lectin; an increase in N-acetylglucosamine structures detected with Lycopersicon esculentum lectin; increased migration and lack of evidence for distinct subunit structure on agarose gels. In membrane extracts, the main difference was the presence of T antigen (Gal beta 1-3GalNAc) in KCS. These results demonstrate alterations in the subunit linkage of mucins in KCS, and suggest that glycosylation, core protein expression and/or post-synthetic modification of ocular surface mucins may also be changed. PMID- 9990336 TI - HSP-derived peptides inducing uveitis and IgG and IgA antibodies. AB - Heat shock protein (HSP) 65 kD-derived peptides, which specifically stimulate T cells from patients with Behcet's disease (BD), are capable of inducing uveitis in rats. Mycobacterial HSP 65 kD and BD-specific peptides were injected into Lewis rats and the development of uveitis was monitored clinically and histologically, and IgG and IgA antibodies were measured using an enzyme-linked immunosorbent assay (ELISA). Rats immunized with HSP peptides that developed uveitis showed significantly higher serum IgG antibody levels to peptide 311-326 (P < 0.05) and the corresponding homologous human peptide 336-351 (P < 0.01) than rats without uveitis. Significant increases in serum IgA antibodies in rats with uveitis were also observed in those immunized with peptides 111-125, 311-326 and 336-351 (P < 0.05). Rats injected with HSP 65 kD showed a rise in IgG antibody levels to peptides 111-125, 154-172 and 311-326 and to a lesser extent, a rise in IgA antibody level to peptide 311-326. HSP showed almost complete inhibition of binding of IgG antibodies to HSP 65 kD, but peptides 111-125, 154-172, 311-326 and 336-351 showed inhibition to a lesser extent in a competitive assay. These results suggest that increases in IgG and IgA antibody levels to specific peptides within HSP, develop in rats with uveitis. The T and B cell epitopes responsible for the development of ocular disease in rats immunized with HSP derived peptides, appear to be similar or identical to those found in patients with the ocular type of BD. PMID- 9990337 TI - Plasmodium falciparum and Plasmodium yoelii: effect of the iron chelation prodrug dexrazoxane on in vitro cultures. AB - To determine if an iron-chelating prodrug that must undergo intracellular hydrolysis to bind iron has antimalarial activity, we examined the action of dexrazoxane on Plasmodium falciparum cultured in human erythrocytes and P. yoelii cultured in mouse hepatocytes. Dexrazoxane was recently approved to protect humans from doxorubucin-induced cardiotoxicity. Using the fluorescent marker calcein, we confirmed that the iron-chelating properties of dexrazoxane are directly related to its ability to undergo hydrolysis. As a single agent, dexrazoxane inhibited synchronized cultures of P. falciparum in human erythrocytes only at suprapharmacologic concentrations (> 200 microM). In combination with desferrioxamine B, dexrazoxane in pharmacologic concentrations (100-200 microM) moderately potentiated inhibition by approximately 20%. In contrast, pharmacologic concentrations of dexrazoxane (50-200 microM) as a single agent inhibited the progression of P. yoelli from sporozoites to schizonts in cultured mouse hepatocytes by 45 to 69% (P < 0.001). These results are consistent with the presence of a dexrazoxane-hydrolyzing enzyme in hepatocytes but not in erythrocytes or malaria parasites. Furthermore, these findings suggest that dexrazoxane must be hydrolyzed to an iron-chelating intermediate before it can inhibit the malaria parasite, and they raise the possibility that the iron chelator prodrug concept might be exploited to synthesize new antimalarial agents. PMID- 9990338 TI - Plasmodium falciparum: enhanced gametocyte formation in vitro in reticulocyte rich blood. AB - Concentrates of late stage parasites of the gametocyte-forming clone HB-3 were mixed with blood rich in reticulocytes from anemic patients, or with normal control blood, and kept under culture conditions for 4 days. Significantly more gametocytes were always formed in the reticulocyte-rich blood than in the control. This was true whether the anemic blood supported a larger asexual parasitemia than the control, or a lower one, or the same and without regard to the cause of the anemia. Gametocytes as a percentage of asexual forms were up to 10 times higher in reticulocyte-rich blood than in normal blood. PMID- 9990339 TI - Cryptosporidium parvum infection in suckling rats: impairment of mucosal permeability and Na(+)-glucose cotransport. AB - Na(+)-glucose transport and transepithelial permeability were investigated during symptomatic acute cryptosporidiosis in newborn rats. The infection resulted in a significant (P < 0.01) decrease in the ileal short-circuit current and a nonsignificant fall in the transepithelial potential difference and conductance. In glucose-stimulated conditions, the rise in ileal short-circuit current and transepithelial permeability were significantly lower in Cryptosporidium parvum infected rats than in controls (delta Isc = 3.24 +/- 1.21 microA.cm-2 vs delta Isc = 5.09 +/- 2.23 microA.cm-2 in infected and control animals, respectively; P < 0.001; delta PD = -0.35 +/- 0.13 mV vs delta PD = -0.44 +/- 0.14 mV for infected and control animals, respectively; P < 0.01). Electrical parameters were not affected by addition of the cyclooxygenase inhibitor indomethacin in either Cryptosporidium-infected newborn rats or controls. Horseradish peroxidase and mannitol flux studies demonstrated a significant decrease (P < 0.05) in transepithelial molecular permeability in infected enterocyte rats, HRP flux = 380, range 68-5570 ng.cm-2, and mannitol flux = 1.06, range, 0.34-1.44%.cm-2.min 1, compared with controls rats, HRP flux = 4446 range, 1121-124,363 ng.cm-2, and mannitol flux = 1.99, range, 0.57-5.09%.cm-2.min-1; P < 0.05. These effects could originate from C. parvum-induced alteration of intracellular trafficking of pinocytosis vesicles and therefore account for the decrease in permeability to solute and macromolecules, together with impaired transcellular nutrient transport, in suckling rats. PMID- 9990340 TI - Plasmodium falciparum: stage-related expression of topoisomerase I. AB - The expression and activity of topoisomerase I (PfTopoI) has been examined during the intraerythrocytic stages of the Plasmodium falciparum life cycle. The promoter is inactive during the early ring stage and becomes active only during the later trophozoite and schizont stages. The PfTOP1 transcript starts to accumulate in the trophozoite stage parasite, decreasing again in the schizont stage. Using both stage-specific Western analysis and immunofluorescent assays we show that PfTopoI is present at low levels in rings and accumulates to approximately equal levels in the trophozoite and schizont stages. Experiments to determine the activity of PfTopoI, using a topoisomerase I relaxation assay, show that there is a low level of PfTopoI activity in both ring and trophozoite stages, but activity increases dramatically in the schizont stage. The PfTopoI activity can be inhibited by treatment with specific antiserum and by the type I topoisomerase-specific inhibitor camptothecin. PMID- 9990341 TI - Plasmodium falciparum: molecular background to strain-specific rosette disruption by glycosaminoglycans and sulfated glycoconjugates. AB - Rosetting, the adhesion of Plasmodium falciparum-infected erythrocytes to uninfected erythrocytes, is a virulent parasite phenotype associated with the occurrence of severe malaria, e.g., cerebral malaria. Compounds with specific anti-rosetting activity are potential therapeutic agents. Glycosaminoglycans and sulfated glycoconjugates were found to disrupt rosettes in a strain- and isolate specific manner. Rosette disruption was strongly connected to the presence of N sulfate groups in heparin/heparan sulfate as demonstrated by modified heparin preparations. This finding was corroborated by the disruption of rosettes with mono- and disaccharides derived from heparin/heparan sulfate that contained N sulfated glucosamine. Furthermore, heparinase III treatment of erythrocyte cultures infected by FCR3S1 (and to some extent TM 284) P. falciparum strains abolished rosetting. Heparinase III treatment of the uninfected erythrocytes prior to mixing with the infected culture impeded formation of rosettes, indicating that the rosetting receptors at least partially are of glycosaminoglycan nature. PMID- 9990342 TI - Nippostrongylus brasiliensis: characterisation of a somatic amphiphilic acetylcholinesterase with properties distinct from the secreted enzymes. AB - We have previously determined that Nippostrongylus brasiliensis secretes three monomeric nonamphiphilic (G1na) variants of acetylcholinesterase (AChE) with broadly similar properties. In this study we have examined AChE expression in somatic extracts of N. brasiliensis and report the identification of an additional enzyme which is not secreted. The enzyme was resolved by sucrose density gradient centrifugation with a sedimentation coefficient of 10.2 S which was shifted to 9.4 S in the presence of Triton X-100, identifying the enzyme as a tetrameric amphiphilic (G4a) form. The amphiphilic properties of this enzyme were confirmed by charge-shift electrophoresis, in which migration was accelerated by interaction with sodium deoxycholate. The enzyme showed low activity with butyrylthiocholine, and a Michaelis constant of 91 +/- 13 microM for acetylthiocholine was determined. It was highly sensitive to the AChE-specific inhibitor bis (4-allyldimethylammoniumphenyl)pentan-3-one dibromide, with an IC50 of 6.5 +/- 0.4 microM, but was also inhibited by the butyrylcholinesterase specific inhibitor tetramonoisopropylpyrophosphortetramide, albeit with a higher IC50 of 46.5 +/- 6.1 microM. This enzyme can therefore be distinguished from the secreted AChEs by its amphiphilic properties, sedimentation in sucrose gradients, and sensitivity to cholinesterase inhibitors. PMID- 9990343 TI - Leishmania major: histone H1 gene expression from the sw3 locus. AB - Histone H1 in the parasitic protozoan Leishmania is a developmentally regulated protein encoded by the sw3 gene. Here we report that histone H1 variants exist in different Leishmania species and strains of L. major and that they are encoded by polymorphic genes. Amplification of the sw3 gene from the genome of three strains of L. major gave rise to different products in each strain, suggesting the presence of a multicopy gene family. In L. major, these genes were all restricted to a 50-kb Bg/II fragment found on a chromosomal band of 1.3 Mb (chromosome 27). The detection of RFLPs in this locus demonstrated its heterogeneity within several species and strains of Leishmania. Two different copies of sw3 (sw3.0 and sw3.1) were identified after screening a cosmid library containing L. major strain Friedlin genomic DNA. They were identical in their 5' UTRs and open reading frames, but differed in their 3' UTRs. With respect to the originally cloned copy of sw3 from L. major strain LV39, their open reading frames lacked a repeat unit of 9 amino acids. Immunoblots of L. guyanensis parasites transfected with these cosmids revealed that both copies could give rise to the histone H1 protein. The characterization of this locus will now make possible a detailed analysis of the function of histone H1 in Leishmania, as well as permit the dissection of the molecular mechanisms governing the developmental regulation of the sw3 gene. PMID- 9990344 TI - Plasmodium falciparum: analysis of the antibody specificity to the surface of the trophozoite-infected erythrocyte. AB - Current opinion supports the view that immunity to the surface of the trophozoite infected erythrocyte (IE) is to Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP-1). Here we provide further evidence using the mutant cell line 1776/C10 which no longer expresses PfEMP-1 at the IE surface, due to a subtelomeric deletion in chromosome 9. We have measured antibody reactivity to this mutant in comparison to it's intact isogenic parent line 1776, which does express PfEMP-1, using the sensitive technique of flow cytometry. IgG-specific antibodies (subclass IgG1) in the plasma of hyperimmune adults, reacted to 1776 but never to the 1776/C10 mutant. Antibody subclasses were also measured in individual plasma samples to the surface of trophozoite-IE. Predominantly IgG1 antibodies were detected, with a few individual plasma having additional IgG3 antibodies. Previous studies have used the agglutination assay to measure sero conversion to PfEMP-1. Here we show that both agglutination and flow cytometric methods are comparable, suggesting that agglutination of trophozoite-IE is mediated by IgG antibodies. Comparison of the isogenic cell lines 1776 and 1776/C10 differing in expression of PfEMP-1 provides further evidence that IgG antibodies, in particular of the cytophilic subclasses, mediate recognition of PfEMP-1. PMID- 9990345 TI - Entamoeba histolytica: signaling through G proteins. AB - The intracellular signaling pathways of Entamoeba histolytica are largely unknown. Although the expression of guanine nucleotide binding proteins (G proteins) is expected from functional studies, their biochemical characterization remains elusive in this protozoan. Using a combination of biochemical and immunological studies, we provide strong evidence for the presence of a Gs protein in amoeba. Our results strengthen our understanding of the signal transduction mechanisms in E. histolytica as potential sites of a new therapeutic strategy. PMID- 9990346 TI - A Trypanosoma brucei bloodstream form mutant deficient in ornithine decarboxylase can protect against wild-type infection in mice. AB - A Trypanosoma brucei bloodstream mutant in which both copies of the ornithine decarboxylase (ODC) gene were knocked out (ODC mutant) was used to determine the biological functions of ODC in T. brucei. Growth of the mutant cells ceased within 12-24 h in regular culture medium deficient in polyamines, but could be rescued by supplementation with 1 mM putrescine. A mouse model of T. brucei infection was used to determine whether the mutant was still infective and was found to develop either extremely low or undetectable levels of parasitemia, suggesting that in T. brucei, ODC activity is essential for establishing an infection. Furthermore, when these mice were subsequently challenged with wild type T. brucei cells expressing the same variant surface glycoprotein (VSG), they did not develop any parasitemia, indicating that inoculating the mice with the attenuated ODC mutant had conferred protection against challenge by wild-type cells. These results were reproduced in C57BL/6J mice deficient in alpha-beta and gamma-delta T-cell receptors. However, no protection was observed in rag-2 knockout mice deficient in both B and T lymphocytes or in C57BL/10J mice deficient only in B lymphocytes. The results thus suggest that the ODC mutant could induce a T-lymphocyte-independent but B-lymphocyte-dependent immunity against wild-type cells of the same VSG. Such a mechanism of immunity has been elicited only by live T. brucei cells, but not by isolated VSGs or radiation killed trypanosomes. This ODC mutant may thus represent a genuinely attenuated T. brucei bloodstream form capable of immunizing mammals against infections by African trypanosomes of the same VSG subtype without causing detectable infection by itself. The observation also raises the interesting likelihood that the in vivo treatment of T. brucei bloodstream forms with alpha-DL difluoromethylornithine is a de facto attenuation of the parasitic organisms, which may very well result in B-lymphocyte-dependent host immune responses to subsequent infections by parasites of the same VSG subtypes. PMID- 9990347 TI - Trypanosoma musculi: tracking parasites and circulating lymphoid cells in host mice. AB - Two aspects of host-parasite relationships that seem worthy of more attention are: (a) the distribution of parasites among host organs in the early course of infection, and (b) the dynamics of host lymphocyte tissue localization and recirculation during the course of infection. We have employed the derivatized aminostyrylpyridinium dye, [125I] I 2P-Di-6-ASP, to provide a relatively stable tag on both a parasite, Trypanosoma musculi, and on host mouse splenocytes, enriched B and T lymphocytes, and natural killer cells. The organ distribution of the parasites, splenocytes, and lymphocytes in recipient, host mice was tracked. Radiolabeled T. musculi localized primarily in the liver with lesser numbers in spleen, lungs, and kidneys. Per unit wet weight, the spleen accumulated parasites most efficiently. When T. musculi were inoculated intraperitoneally, most of them remained in the peritoneal space and the numbers that gained access to liver, lungs, and spleen were significantly smaller than in mice inoculated intravenously. The acquisition of parasites by the spleen (and lungs) of mice with an existing T. musculi infection was markedly inhibited. This was true also of syngeneic splenocytes and lymphocytes. In addition, lymphocytes from infected mice were significantly less likely to take residence in the spleens of normal recipient mice and were especially unlikely to localize in the spleens of infected recipients. These and other findings suggested that the inability of circulating lymphocytes to gain access to lymphoid tissues in infected mice, coupled with the poor ability of those tissues to sequester parasite antigens, could account for the known prolonged delay in the development of curative antibody response characteristic of T. musculi-infected mice. It is likely that the marked disruption of lymphoid tissue histoarchitecture that is typical of T. musculi infection contributes significantly to the failure of the tissues to sequester parasites and lymphocytes. Because lymphoid tissue disruption is seen in many parasitic infections, the findings reported here may have fairly broad relevance. In any case, the procedure described here for labeling parasites and lymphocytes should be of general utility for tracking their disposition in vivo. PMID- 9990348 TI - Trypanosoma musculi: compared levels of parasitosis in wild and laboratory strains of Mus musculus mice. PMID- 9990349 TI - Trypanosoma brucei: generation of specific antisera to recombinant variant surface glycoproteins. PMID- 9990350 TI - Clinical, demographic, and immunohistologic features of vancomycin-induced linear IgA bullous disease of the skin. Report of 2 cases and review of the literature. AB - Administration of intravenous vancomycin has been associated with the development of linear IgA bullous disease (LABD). In contrast to the idiopathic variant, vancomycin-induced LABD (VILABD) appears to be more transient and to be associated with lower morbidity. The characteristics of this entity remain undefined. Our analysis of clinical, demographic, and immunopathologic features of 2 new and 14 previously reported patients with VILABD reveals that VILABD is clinically and immunopathologically indistinguishable from its idiopathic variant. A variety of premorbid conditions and concomitant medications were observed, none of which was consistently associated with the development of VILABD. VILABD occurs independently of vancomycin trough levels, resolves promptly upon discontinuation of vancomycin, and recurs more severely and with shorter onset latency with vancomycin rechallenge. This entity should be recognized as 1 of the adverse cutaneous effects of intravenous vancomycin, and warrants prompt diagnosis through direct immunofluorescence skin examination. PMID- 9990351 TI - X-linked recessive spondyloepiphyseal dysplasia tarda. Clinical and radiographic evolution in a 6-generation kindred and review of the literature. AB - We characterize the clinical and radiographic evolution of X-linked recessive spondyloepiphyseal dysplasia tarda (SEDT) in a 6-generation kindred from Arkansas (SEDT(AK)). Our observations show the natural progression of SEDT(AK) and enable carrier detection by radiographic study. We find that, SEDT(AK) manifests as a postnatal defect. Affected hemizygous males can have radiographically normal vertebrae at birth. The pathogenesis seems to involve a developmental disturbance in endochondral bone formation that is reflected most dramatically in vertebrae by a radiographically inapparent ring apophysis. This defect leads to distinctive malformation of the anterior margins of the lumbar vertebrae during childhood. Subsequently, there is degeneration of intervertebral discs and destruction of spinal facet joints. In the femur, the head, neck, and distal condyles are abnormally shaped and become distorted so that osteoarthritis of the hip is not uncommon. Obligate carrier females heterozygous for the SEDT(AK) gene defect demonstrate several similar but more subtle skeletal abnormalities beginning in early adult life. These women seem to be troubled frequently by arthralgia by middle age. The cumulative findings in SEDT(AK) implicate a defect in a gene at Xp22.2-22.1 that engenders a relatively mild disturbance in endochondral bone formation, especially in the axial skeleton. Accounts of large, well characterized SEDT kindreds remain essential to appreciate fully any interfamily variability of disease expression and to understand better the pathogenesis of the SEDT defect on the X chromosome. PMID- 9990352 TI - Churg-Strauss syndrome. Clinical study and long-term follow-up of 96 patients. AB - Churg-Strauss syndrome (CSS) is a systemic vasculitis characterized by the presence of asthma, hypereosinophilia, and necrotizing vasculitis with extravascular eosinophil granulomas. In this retrospective study of 96 patients between 1963 and 1995, we analyzed clinical manifestations, identified prognostic factors, and assessed the long-term outcome. CSS was diagnosed when asthma, hypereosinophilia > 1,500/mm3 or > 10%, and clinical manifestations consistent with systemic vasculitis, with or without histologic evidence, were present. Asthma was the most frequently observed manifestation at presentation, with mononeuritis multiplex the second. Other common manifestations were weight loss, fever, myalgia, skin involvement, paranasal sinusitis, arthralgia, pulmonary infiltrate, and gastrointestinal involvement. Mean eosinophilia at presentation was 7.193 +/- 6.706/mm3; ANCA, present in 20 of 42 (47.6%) patients, predominantly gave the perinuclear labeling pattern. All the patients were treated with corticosteroids alone or in combination with cyclophosphamide or plasma exchanges. Clinical remission was obtained in 91.5%; 22 (25.6%) patients relapsed. Twenty-three patients died during follow-up: 11 of these deaths were directly due to vasculitis. The presence of severe gastrointestinal tract or myocardial involvement was significantly associated with a poor clinical outcome. The long-term prognosis of CSS is good and does not differ from that of polyarteritis nodosa, although most patients need low doses of oral corticosteroids for persistent asthma, even many years after clinical recovery from vasculitis. PMID- 9990353 TI - Lymphocutaneous syndrome. A review of non-sporothrix causes. AB - The lymphocutaneous syndrome can be caused by a number of diverse microorganisms requiring very different antimicrobial therapy for resolution. The epidemiology and geographic occurrence of the infection often can provide important first clues to the microbiologic etiology. Accurate diagnosis can be accomplished usually by punch or wedge biopsy of a primary lesion or proximal subcutaneous nodule submitted for histopathologic examination and culture. The microbiology laboratory staff should be alerted to the diagnostic possibilities so that appropriate cultural and incubation techniques, procedures, and precautions can be initiated. Provision of a correct microbiologic diagnosis and institution of appropriate antimicrobial therapy will result in a complete cure in almost all instances. Adjunctive surgical debridement may be required for certain organisms such as Nocardia or Mycobacterium chelonae. PMID- 9990354 TI - Primary cutaneous B-cell lymphoma: how useful is the new European Organization for Research and Treatment of Cancer (EORTC) classification? AB - The classification of non-Hodgkin's lymphoma has undergone extensive revision in recent years, particularly with the development of immunophenotypic and genotypic criteria. While most general pathologists now rely upon the Revised European and American Classification of Lymphoma neoplasms (REAL), the cutaneous lymphoma project group of the European Organization for Research and Treatment of Cancer (EORTC) has put forward its own proposal for the classification of primary cutaneous lymphomas. While this is understandable in the context of cutaneous T cell lymphoma, the EORTC classification of primary cutaneous B-cell lymphoma has proved more controversial: first, because chromosomal changes are largely excluded; secondly, because follicle centre cell lymphoma in the skin is imprecisely defined; and thirdly, because large B-cell lymphoma of the leg is included as a separate entity. This review identifies the main differences between the two systems of classifying B-cell lymphomas in the skin, and the areas of research required to clarify some of the outstanding issues. Pathologists are unlikely to adopt the EORTC proposals for B-cell neoplasms until these issues have been resolved. PMID- 9990355 TI - Upregulation of the calcium-dependent protease, calpain, during keratinocyte differentiation. AB - Calpain is a ubiquitous neutral calcium-activated thiol protease that is implicated in various cellular functions including exocytosis, cell fusion, apoptosis and proliferation. The calpain system is composed of the enzymes mu calpain and m-calpain and their endogenous inhibitor, calpastatin. We employed the spontaneously immortalized human HaCaT keratinocytes, which retain their ability to differentiate in vitro and in vivo, to study the modulation of the calpain system during keratinocyte differentiation. The cellular levels of keratinocyte differentiation markers and of the components of the calpain system were monitored by immunoblotting. Three established differentiation stimuli: increase in cell density as a function of time in culture, elevation of extracellular calcium concentration and exposure to 1,25-dihydroxyvitamin D3 enhanced the expression of the three keratinocyte differentiation markers keratin 10, involucrin and transglutaminase. The differentiation of HaCaT cells was accompanied by elevation of the components of the calpain system, although the pattern of increase varied according to the specific differentiation stimulus. A higher increase in calpains as compared with the increase in calpastatin suggests an increase in net calpain activity during differentiation. Such an increase may play a part in the differentiation process itself and/or in the regulation of key events in differentiating keratinocyte metabolism. PMID- 9990356 TI - Differential patterns of filaggrin expression in lamellar ichthyosis. AB - Lamellar ichthyosis (LI) is a rare genetic and congenital disturbance of keratinization that is phenotypically and genotypically heterogeneous. Filaggrin is one of the major components of the stratum corneum situated in the protein matrix and the cornified envelope. In view of the heterogeneity of LI, this study aimed at exploring filaggrin expression in the skin of patients suffering from the disease. Epidermal filaggrin expression was determined using immunohistochemical techniques and Western blot in 12 patients with LI and the findings were compared with those observed in four normal controls and eight patients with ichthyosis vulgaris. With Western blot, six different patterns of filaggrin expression were detected. The patients with similar clinical manifestations showed a similar pattern, as did members of the same family. Overall, higher filaggrin expression in scales correlated with a better prognosis. In patients receiving retinoids no variations in filaggrin expression during treatment were detected. Our results suggest that LI is heterogeneous as regards filaggrin expression. Filaggrin could therefore be used as a prognostic marker as well as being a marker of the basic defect involved in LI. PMID- 9990357 TI - Vitiligo melanocytes in long-term culture show normal constitutive and cytokine induced expression of intercellular adhesion molecule-1 and major histocompatibility complex class I and class II molecules. AB - The aetiology of vitiligo remains unclear. An autoimmune involvement has been suggested and, in this study, we examine whether melanocytes cultured from unaffected regions of the skin of vitiligo patients are more susceptible to immune attack by investigating constitutive and cytokine-stimulated expression of intercellular adhesion molecule-1 (ICAM-1) (under three media variants) and major histocompatibility complex (MHC) class I and class II (under one medium). Both normal and vitiligo melanocytes had similarly low constitutive expression of ICAM 1 and MHC class II molecules, whereas > 95% of cells had high constitutive expression of MHC class I. Normal and vitiligo melanocytes showed similar and significant increases in the expression of all three immune-related molecules in response to the cytokine, interferon-gamma. The expression of ICAM-1 was also similarly increased by the cytokine, tumour necrosis factor-alpha in both cells. Additionally, it was noted that, once the melanocyte cultures were established under experimental conditions, the rate of proliferation of vitiligo melanocytes did not differ significantly from that of normal melanocytes. In conclusion, we suggest that vitiligo melanocytes, once in culture, do not have intrinsic differences from normal melanocytes with respect to the expression of immune related molecules. PMID- 9990358 TI - Evidence for loss of heterozygosity in human psoriatic lesions. AB - Psoriasis, a disease of human skin, is characterized by abnormal differentiation and hyperproliferation of keratinocytes; it has a genetic background. Using 11 highly polymorphic microsatellite markers on eight chromosome arms, we performed an allelotype analysis in 14 psoriatic plaques, in order to reveal any chromosome deletions involved in the development of the disease. We detected loss of heterozygosity (LOH) on at least one microsatellite marker in nine of 14 (64%) cases. We also observed particular genetic loci altered with LOH, on chromosomes 3p, 7p/q and 8p. Our results suggest that LOH is an important phenomenon in the development of psoriatic plaques, providing evidence for deletion of regulatory genes. PMID- 9990359 TI - HLA-DRB1*0701 and DRB1*1401 are associated with genetic susceptibility to psoriasis vulgaris in a Taiwanese population. AB - We analysed the allelic frequencies of class II human leucocyte antigen (HLA) DRB1, DQA1, DQB1 and DPB1 by polymerase chain reaction/sequence-specific oligonucleotide probe hybridization typing in 76 Taiwanese psoriasis vulgaris (PSV) patients and 238 Taiwanese non-psoriatic controls. The analysis revealed the following: (i) the DRB1*0701 allele was positively associated with PSV (relative risk, RR = 6.4, corrected P-value, Pc < or = 0.001); (ii) the DRB1*1401 allele was positively associated with type I PSV (age at onset < 40 years) (RR = 3.5, Pc < or = 0.001); (iii) the DQA1*0501 allele was negatively associated with PSV (RR = 0.4, Pc < or = 0.001); (iv) there was no significant association of HLA DP genes with PSV; and (v) there was a strong association of beta-chain phenylalanine at position 37 (Phe 37) and glutamate or glutamine at position 74 (Glu 74/Gln 74) with PSV (RR = 3.5, Pc < or = 0.001 for the association of Phe 37 with PSV: RR = 2.2, Pc < or = 0.001 for the association of Glu 74/Gln 74 with PSV). The positive association between PSV and the DRB1*0701 allele is consistent with previous reports. The negative association of the DQA1*0501 allele is reported only in Finland, whereas the positive association between PSV and the DRB1*1401 allele has never been described before. Trans-racial studies may shed further light on the association of class II HLA alleles or other closely linked genes with the development of PSV. Phe 37 (a large, non-polar amino acid) and Glu 74/Gln 74 (both negatively charged amino acids) were the polymorphic residues in pockets 9 and 4, respectively, of the beta-chain, which may have increased their affinity for the small non-polar amino acids and basic amino acids of the psoriatic antigen peptide, thereby activating the T lymphocytes. This finding may facilitate the identification of a psoriatic antigen. PMID- 9990360 TI - Calcipotriol inhibits the proliferation of hyperproliferative CD29 positive keratinocytes in psoriatic epidermis in the absence of an effect on the function and number of antigen-presenting cells. AB - The aim of this study was to elucidate some of the possible mechanisms of action of the vitamin D analogue calcipotriol in vivo. Calcipotriol is finding increasing use in the treatment of psoriasis, but the primary target cell in vivo has not yet been identified. We treated psoriatic patients and healthy volunteers with calcipotriol and placebo ointment for 4 and 7 days, and obtained epidermal cell suspensions from treated areas. Epidermal cells were cocultured with autologous T cells, isolated from peripheral blood, in the absence or the presence of a classical antigen or a superantigen. In both psoriatic and normal skin, calcipotriol treatment did not alter the capacity of epidermal antigen presenting cells to stimulate the proliferation of autologous T cells, either in the absence or in the presence of exogenous antigen. Epidermal cell suspensions were analysed further by staining for infiltrating leucocytes (CD45+) and Langerhans cells (CD1a+). Flow cytometric analysis showed that calcipotriol did not alter the number of CD45+ cells or Langerhans cells in psoriatic skin. These results indicate that calcipotriol does not alter either the number of the function of epidermal antigen-presenting cells in psoriatic epidermis. In contrast, we found that calcipotriol significantly inhibited the proliferation of epidermal cells isolated from psoriatic skin after in vivo treatment, as determined by propidium iodide staining and flow cytometry. More specifically, we stained for CD29+ keratinocytes and found an even more significant reduction in proliferative capacity. This cell type contains the population of hyperproliferative keratinocytes in psoriatic epidermis. In conclusion, calcipotriol seems to act via an inhibitory effect on hyperproliferative basal keratinocytes of psoriatic epidermis, rather than via an effect on infiltrating leucocytes, including antigen-presenting cells. PMID- 9990361 TI - The novel ascomycin derivative SDZ ASM 981 is effective for psoriasis when used topically under occlusion. AB - Topical SDZ ASM 981 has been found to be highly effective in preclinical models of T-cell-mediated skin disease. T cell activation is crucial in the pathogenesis of psoriasis. It has been hypothesized that SDZ ASM 981 may prove to be an effective treatment for chronic plaque psoriasis. Therefore, the study objective was to determine the efficacy, tolerability and safety of the new topical macrolactam, SDZ ASM 981, for chronic plaque psoriasis. Ten patients with chronic plaque-type psoriasis were treated with SDZ ASM 981 (0.3% and 1.0%), the corresponding ointment base (placebo) and open-labelled clobetasol-17-propionate ointment (0.05%) in a randomized, double-blind, within-subject comparison for 2 weeks using the microplaque assay. Evaluation was performed by daily determination of clinical scores for erythema and induration. The results of the study showed that, after 2 weeks of treatment, total scores described by 92% for clobetasol, by 82% for 1 SDZ ASM 981, by 63% for 0.3% SDZ ASM 981 and by 18% for the ointment base (placebo). No adverse drug effects were seen in any patient throughout the study. We conclude from our results that the new macrolactam SDZ ASM 981 (1%) is similar to clobetasol-17-propionate (0.05%) in plaque-type psoriasis when applied topically under occlusion for 2 weeks using the microplaque assay. PMID- 9990362 TI - Double-blind placebo-controlled study of long-term low-dose cyclosporin in the treatment of palmoplantar pustulosis. AB - We previously showed in a double-blind, placebo-controlled study that cyclosporin at a dose of 2.5 mg/kg per day is an effective treatment for palmoplantar pustulosis (PPP). In the present randomized, double-blind, placebo-controlled multicentre study we treated 58 PPP patients with placebo or cyclosporin at an initial dose of 1 mg/kg per day. Disease activity was calculated from the number of fresh pustules. Treatment success was defined as the number of fresh pustules not exceeding 50% of the patients' own baseline pustule number. In cases of treatment success the dose of the test medication was not increased and the treatment was kept blinded for a maximum of 12 months. Blinding was broken only on treatment failure of the initial test medication dose. The mean blinded treatment time was 5.1 months for the patients receiving cyclosporin and 2.1 months for placebo (P < 0.01). Treatment was kept blinded for 12 months for seven patients in the cyclosporin and two in the placebo group (P < 0.05). Patients whose treatment code was broken continued in an open dose-finding part of the study with dose adjustments of cyclosporin every second month. In cases of treatment failure the dose of cyclosporin was increased in steps of 1 mg/kg per day; in cases of treatment success the cyclosporin dose was decreased by 1 mg/kg per day. The minimum and maximum doses were 1 and 4 mg/kg per day, respectively. The mean effective dose during the dose-finding part was between 1.2 and 1.7 mg/kg per day. Two patients did not respond to the highest dose of 4 mg/kg per day. In two patients serum creatinine levels increased by > 30% of their own baseline. The other main adverse events were hypertension (seven patients) and hypertrichosis (six patients). After stopping cyclosporin treatment the mean number of fresh pustules showed a maximum after 2 weeks with a continuous decline after that. Twelve months after completing the treatment the mean number of pustules was reduced to 20.0 compared with 63.6 at baseline (P < 0.001); 11 patients were free from pustules and two of these were totally cleared. We conclude that cyclosporin at 1-2 mg/kg per day is an effective and well tolerated treatment for PPP in most patients. PMID- 9990363 TI - A comparison of treatment with dithranol and calcipotriol on the clinical severity and quality of life in patients with psoriasis. AB - In a multicentre, randomized, open study, 306 patients of either sex, over 18 years of age with stable chronic plaque psoriasis > 100 cm2 in surface area, and who gave informed consent, applied Dovonex (calcipotriol) ointment (50 micrograms/g) twice daily or Dithrocream (short-contact dithranol) 0.1-2% for up to 3 months. The number of patients 'cleared' or with 'marked improvement' at the end of treatment were: investigators' assessment--calcipotriol 92 of 153 (60.1%); dithranol 67 of 131 (51.1%); odds ratio 1.44 [95% confidence interval (CI) 0.90, 2.31; P = 0.128]; patients' assessment--calcipotriol 93 of 153 (60.8%); dithranol 65 of 131 (49.6%); odds ratio 1.57 (95% CI 0.98, 2.52; P = 0.059). Significant improvement in patients' quality of life as assessed by the Psoriasis Disability Index (PDI) and the Sickness Impact Profile (SIP) were seen in both treatment groups. Reduction in the total mean score for PDI was 6.5 in the calcipotriol group (95% CI 4.4, 8.6; P = 0.001) and 3.7 in the dithranol group (95% CI 1.1, 6.3; P = 0.005). The reduction in the total mean score for SIP was 2.8 in the calcipotriol group (95% CI 1.4, 4.3; P < 0.001) and 1.7 in the dithranol group (95% CI 0.2, 3.1; P = 0.024). Calcipotriol treatment tended to have advantages over treatment with dithranol in improving quality of life. PMID- 9990364 TI - Increased levels of enkephalin following natural sunlight (combined with salt water bathing at the Dead Sea) and ultraviolet A irradiation. AB - The opioid peptides enkephalins have been shown to modulate inflammatory responses and keratinocyte proliferation and differentiation. Furthermore, increased levels of enkephalin are present in psoriatic lesions. The purpose of the present study was to determine the effect of natural sunlight combined with salt water bathing in the Dead Sea on the methionine-enkephalin (e.n.k.) level in psoriatic skin. Ten patients were treated at the Dead Sea for 4 weeks, and keratotome biopsies were obtained before and after treatment. The amount of enkephalin extracted from the biopsies was measured by radioimmunoassay. Treatment at the Dead Sea resulted in a complete clinical clearance of psoriasis, and immunohistochemical stainings of lesional skin showed that the treatment decreased both epidermal thickness/parakeratosis and the dermal infiltration of CD3- and CD68-positive cells, although the number of CD3- and CD68-positive cells became normal in only two of the 10 cases. However, there was only a slight decrease in the mean enk levels (21%). Furthermore, the level of enk was high in non-lesional psoriatic skin after treatment at the Dead Sea, and immunostaining showed that, in some patients, the treatment induced a mild epidermal hyperplasia and a dermal infiltration of CD3- and CD68-positive cells. Enkephalin-like immunoreactivity was detected in the cytoplasm of both epidermal keratinocytes and dermal infiltrating cells. To determine whether the relatively high skin enk levels after treatment at the Dead Sea was caused by ultraviolet (UV) radiation, normal volunteers were exposed to a single dose of UVA and UVB (2 minimal erythema doses). UVA, but not UVB, irradiation stimulated the mean enk level in the irradiated skin by about sixfold. Furthermore, multiple whole-body UVA irradiations not only resulted in increased skin levels of enk, but also in increased plasma levels. In conclusion, natural sunlight combined with salt water bathing cleared psoriasis without causing a significant decrease in lesional enk levels. Furthermore, non-lesional enk levels were increased. These findings may be the result of a direct stimulatory effect of UVA irradiation on enk formation in the skin. It is possible that the increased circulating levels of enk after UV exposure may contribute to the beneficial effects of UVA irradiation. PMID- 9990365 TI - Circulating type I collagen degradation products: a new serum marker for clinical severity in patients with scleroderma? AB - Systemic sclerosis (SSc; scleroderma) results in the excessive deposition of extracellular matrix components in affected organs. This is partly due to enhanced synthesis; however, the role of degradative processes in this disease is still poorly understood. Sera of 32 patients with SSc (22 with the diffuse, 10 with the limited form) and of six patients with morphoea were assessed using radioimmunoassays for the cross-linked carboxy terminal telopeptide of type I collagen (ICTP) and for the amino terminal propeptide of type I procollagen (PINP) reflecting type I collagen degradation and synthesis, respectively. In 27 of the 32 patients with SSc, the concentration of ICTP was above the upper limit of the normal value (4.6 micrograms/L) and the mean level was clearly elevated at 7.92 micrograms/L. The ICTP concentration correlated with the skin score measuring the extent of the lesions, whereas no such correlation was found for PINP. The ICTP antigen in serum, studied by immunoblotting, had a molecular weight of about twice that of the trypsin-generated fragment isolated from human bone collagen. The mean concentration of serum PINP was 43.9 micrograms/L and no patient exceeded the upper limit of the normal range (80 micrograms/L). We report here for the first time that the concentration of the type I collagen degradation product ICTP in serum shows a close correlation with the extent of skin fibrosis in patients with SSc. We conclude that the increased deposition of type I collagen in this disease is accompanied by an increased turnover of this molecule, indicating a more complex derangement of synthetic and degradative processes than previously acknowledged. PMID- 9990366 TI - Increased levels of interleukin 5 are associated with the generation of eosinophilia in drug-induced hypersensitivity syndrome. AB - Hypersensitivity syndrome (HSS) usually refers to severe drug eruption associated with systemic symptoms and eosinophilia. Interleukin (IL)-5 regulates eosinophil counts with the help of IL-3 and granulocyte-macrophage colony-stimulating factor (GM-CSF). Blood IL-5 levels have been reported to be increased in patients with eosinophilia secondary to parasitic infections or idiopathic eosinophilia, but have never been evaluated in drug-induced eosinophilia. The aim of our study was to determine whether IL-5, IL-3 and GM-CSF are involved in eosinophilia in patients with drug-induced HSS. Plasma levels of IL-3, IL-5 and GM-CSF were assayed by ELISA in seven patients with drug-induced HSS, in eight patients with cutaneous adverse drug reactions not associated with eosinophilia, and in five patients with eosinophilia unrelated to drug treatment. IL-5 levels were normal in all eight patients with drug eruptions without eosinophilia, and increased in five of the seven patients with HSS. In the latter patients, IL-5 levels peaked several days before highest eosinophil counts were noted, and returned to normal within a few days, even when eosinophilia persisted. In patients with eosinophilia unrelated to drug treatment, IL-5 levels, although significantly increased remained lower than in HSS patients. IL-3 and GM-CSF could not be detected in any group, at any time. Our results show that IL-5 is involved in drug-related eosinophilia. As IL-5 production was only involved in the early stages of the reaction, it is suggested that IL-5 mainly derives from activated lymphocytes rather than eosinophils. Our results support the clinical relevance of previous in vitro findings. Further studies are needed to test whether assays of IL-5 production by lymphocytes of patients stimulated by the suspected drug and/or its metabolites, are useful in establishing causality in drug-induced reactions associated with eosinophilia. PMID- 9990367 TI - The prevalence and determinants of solar keratoses at a subtropical latitude (Queensland, Australia). AB - We report the association between skin pigmentation and individual sun exposure, and the occurrence of solar keratoses (SKs) in an unselected population, quantified for the first time. SKs were examined in a representative sample of 197 residents of the community of Nambour in Queensland, Australia. Estimates of sun exposure were combined with a measure of ultraviolet (UV) flux to estimate actual UV exposure, both occupational and recreational, during childhood and adult life. The number of episodes of painful sunburn was used as a measure of intermittent, intense UV exposure. Eight-three participants (43%) had at least one SK, while 35 (18%) had more than 10 SKs diagnosed. The age- and sex-adjusted odds ratios (ORs) for the development of SKs were higher in individuals with fair (OR = 14.1) or medium skin (OR = 6.5), compared with olive-skinned individuals. Individuals with poor ability to develop a suntan were similarly at increased risk compared with others. High levels of occupational UV exposure during adult life were confirmed as being strongly associated with prevalent SKs (OR = 2.4 for heavy/maximal adult exposure), with an even stronger association seen in those individuals with multiple SKs (OR = 4.3 for maximal adult exposure). Although no clear association was demonstrated between SK prevalence and accumulated childhood sun exposure, a history of even one episode of sunburn in childhood was strongly associated with SK prevalence (peak OR of 5.9 for one sunburn). PMID- 9990368 TI - The influence of cultural and educational factors on the validity of symptom and diagnosis questions for atopic eczema. AB - Valid questions for atopic eczema are necessary to identify risk factors in epidemiological studies. We have examined the influence of cultural and educational factors on the validity of some questions on atopic eczema used in the International Study of Asthma and Allergies in Childhood by using data from a cross-sectional study on 1511 children aged 6 years from East and West Germany. We tested three questions in relation to a point prevalence of atopic eczema as recorded by a dermatologist: (i) has a physician ever diagnosed eczema in your child? (ii) Has your child ever had an itchy rash which came and went for at least 6 months? (iii) Has your child ever had 'neurodermatitis' (atopic eczema, endogenous eczema)? The point prevalence of atopic eczema on the day of investigation was 11.1% (134 of 1217). According to the questionnaire, 15.7% of the children had had physician-diagnosed eczema, 14.1% had had neurodermatitis and 11.3% had had an itchy rash for > 6 months. Fifty-one per cent of parents who had a child with atopic eczema on the day of investigation said that their child had had an itchy rash which came and went for at least 6 months. This sensitivity value is less than that found in another community survey conducted in the U.K., suggesting that the German wording of the question seems to mean something more severe to the parents than the English one. The education of the parents had an influence on the validity of the three questions: parents with < 10 years of schooling often answered symptom and diagnosis questions less positively. Parents with academic degrees, contrary to expectation, did not answer most precisely, this being especially true for the symptom questions. The association between symptom questions and clinical diagnosis was higher in West than in East Germany. We compared lifetime eczema symptoms and diagnosis with a point prevalence clinical diagnosis. In the absence of knowledge of how extraneous factors measured in this paper can affect diseases chronicity, it is difficult to say with certainty that such factors affect the validity of symptom and diagnosis questions on atopic eczema. Our study suggests that more studies are needed to examine the influence of social class, education and location on the validity of symptom questionnaires for atopic eczema. Until then, we recommend that information about such variables should be gathered routinely. PMID- 9990369 TI - Elevated expression of epidermal ornithine decarboxylase mRNA in scleroderma. AB - Using in situ hybridization techniques, we examined the expression of ornithine decarboxylase (ODC) mRNA in the skin of five patients with systemic sclerosis (SSc) and five normal controls. Sections treated with an anti-sense probe showed concentrated grains exclusively in the epidermis of SSc patients, but not in that of normal controls. Because our subcloned anti-sense probe specifically hybridizes with ODC mRNA, these findings indicate that the expression of ODC mRNA is elevated in SSc epidermis. Possibly polyamines have an important part to play in the skin changes of SSc. PMID- 9990370 TI - Serum concentrations of vascular endothelial growth factor in collagen diseases. AB - Vascular endothelial growth factor (VEGF) is an angiogenic cytokine which has been reported to be important in the pathogenesis of rheumatoid arthritis (RA). In this study, the serum level of VEGF was measured using enzyme-linked immunosorbent assay in 17 patients with systemic lupus erythematosus, 49 patients with polymyositis/dermatomyositis (PM/DM), 40 patients with systemic lupus erythematosus, 49 patients with polymyositis/dermatomyositis (PM/DM), 40 patients with systemic sclerosis (SSc), 11 patients with RA and 20 control subjects. The VEGF level was 184 +/- 62 pg/mL (mean +/- SD) in the serum of normal individuals. The mean VEGF levels in the patients with PM/DM or RA were significantly higher than in the normal controls. In 21 of the 49 patients with PM/DM and nine of the 11 patients with RA, the serum VEGF level was considered to be elevated. In patients with SSc, those with diffuse cutaneous SSc showed elevated VEGF levels in comparison with normal controls. An elevated serum VEGF level was correlated with the frequency of lung fibrosis and reduced vital capacity in the patients with SSc. PMID- 9990371 TI - Non-human immunodeficiency virus Kaposi's sarcoma can be effectively treated with low-dose interferon-alpha despite the persistence of herpesvirus-8. AB - Three patients, negative for human immunodeficiency virus (HIV), with histologically and polymerase chain reaction-proven non-HIV Kaposi's sarcoma who received low-dose interferon (IFN) as first-line treatment because of disseminated symptomatic disease are reported. Applying 3-18 million IU of IFN alpha 2a per day, 3 days a week, subcutaneously for 8-20 months, major responses were achieved in all three cases. Tumour regression was observed within 4 months and has continued for 57 and 18 months to date (cases 1 and 2, respectively). Influenza-like symptoms, including fever, headaches and fatigue, were mild side effects. However, in the third patient interferon injections had to be stopped because of hepatic enzyme elevation. Including this case report, 27 non-HIV Kaposi's sarcoma patients subcutaneously treated with IFN-alpha have been reported in literature. Most therapy regimens included 3-18 million IU IFN-alpha per day for 3 days a week. Twenty of 27 patients, or 74%, responded to therapy, whereas seven patients or 26% had stable or progressive disease. Relapse after IFN withdrawal can occur but is frequently delayed and limited, as in case 1. Following the response to IFN treatment, human herpesvirus-8 DNA was detected in the blood mononuclear cells of all three patients, possibly contributing to future relapses. PMID- 9990372 TI - Ichthyosiform erythroderma and cardiomyopathy: report of two cases and review of the literature. AB - We report two children with ichthyosiform erythroderma who at the ages of 9 weeks and 8 years, respectively, developed dilated cardiomyopathy, which was fatal in one and required heart transplantation in the other. A link between these conditions is considered likely, either as a primary genetic syndrome or secondary to micronutrient deficiency and/or infection. Owing to its insidious onset, cardiomyopathy may be overlooked, or symptoms attributed to the other conditions such as severe infections and failure to thrive that are common in these patients. We therefore recommend that children with congenital erythroderma are monitored closely, clinically and with echocardiography, for cardiomyopathy. PMID- 9990373 TI - Proteus syndrome with widespread portwine stain naevus. AB - Proteus syndrome is a rare condition comprising asymmetrical overgrowth of different parts of the body in association with various cutaneous abnormalities. We describe a 3-year-old boy with Proteus syndrome, who presented with hemihypertrophy of the right leg, asymmetric macrodactyly, subcutaneous masses and a widespread portwine stain interspersed with angiokeratomas on the right leg, scrotum and on the middle and left side of the back. Doppler ultrasound of the right leg did not show hypercirculation, but did reveal the absence of the right superficial femoral vein. PMID- 9990374 TI - Pyoderma gangrenosum in a child with congenital partial deficiency of leucocyte adherence glycoproteins. AB - Congenital deficiency of beta 2 integrin leucocyte adhesion molecules is a rare immunodeficiency and is often fatal. Neutrophils are unable to bind to ligands on the endothelium, and so cannot leave the circulation during inflammation or infection. When leucocyte adhesion deficiency (LAD) is caused by abnormally low expression of beta 2 integrins, it is termed LAD type 1. We describe a 5-year-old girl with a history of recurrent bacterial infections since early childhood who developed necrotic skin ulcers resembling pyoderma gangrenosum and a persistent circulating neutrophilia. Histologically, the lesions showed deep ulceration with a diffuse lymphohistiocytic infiltrate, but with a relative sparsity of neutrophils. Subsequent investigation revealed a complete absence of CD11a/CD18 beta 2 integrins on the surface of the patient's neutrophils, confirming the diagnosis of LAD type 1. The ulcers responded to treatment with oral prednisolone and colchicine. PMID- 9990375 TI - Cutaneous necrosis by cold agglutinins associated with glomeruloid reactive angioendotheliomatosis. AB - The cold agglutinin syndrome is a haemolytic disorder that can cause skin lesions, mainly on the acral areas, with acrocyanosis being the most frequent manifestation. Cutaneous necrosis due to cold agglutinins is very rare. Reactive angioendotheliomatosis (RAE) is an uncommon condition that exclusively affects the skin, characterized by a hyperplasia of endothelial cells and pericytes that can result in the formation of glomeruloid structures. The association of cold agglutinin syndrome with glomeruloid RAE has not been previously described. We report a 70-year-old man diagnosed as having a B-cell low-grade non-Hodgkin's lymphoma. He had two episodes of cutaneous necrosis in acral areas which were related to exposure to cold and due to IgM anti-I(T) cold agglutinins. Biopsy specimens showed vessel proliferations composed of dilated vascular spaces in the dermis and subcutis. Some vessel lumina were partially occluded by eosinophilic thrombi of fibrin and erythrocytes. Numerous closely packed capillaries were observed within pre-existing dilated vessels. This intravascular proliferation of capillaries displayed a glomeruloid pattern. We emphasize the possible presence of a cold agglutinin syndrome in patients with skin necrosis and findings of RAE with a glomeruloid pattern. Cold agglutinaemia may cause these distinctive histological changes. PMID- 9990376 TI - Lymphocytic autoimmune hidradenitis, cutaneous leucocytoclastic vasculitis and primary Sjogren's syndrome. AB - We describe a 60-year-old woman with primary Sjogren's syndrome, mixed cryoglobulinaemia and cutaneous leucocytoclastic vasculitis who developed generalized hypohidrosis with a markedly decreased sweating response to pilocarpine chloride. Skin biopsies demonstrated dense peri-eccrine lymphocytic infiltrates in the lower reticular dermis, with glandular atrophy. From previous studies it is evident that although patients with Sjogren's syndrome commonly have skin dryness, a lymphocytic hidradenitis has been documented only in a few cases. The histological findings in this case support the role of autoimmune hidradenitis in the development of hypohidrosis in Sjogren's syndrome. PMID- 9990377 TI - Cutaneous mucinoses and HIV infection. AB - In the last few years cutaneous mucinoses have been reported with increased frequency in HIV patients. We report the occurrence of scleredema, reticular erythematous mucinosis and lichen myxoedematosus in three different HIV-infected patients, review the literature and discuss the possible relationship between mucin deposits and HIV infection. This is the first report of scleredema and the second of reticular erythematous mucinosis in an HIV-infected patient. Only the association of HIV infection with lichen myxoedematosus seems to be more than coincidental. PMID- 9990378 TI - Lifelong severe verrucosis associated with human papillomavirus type 2: report of a case with a 38-year follow-up. AB - We describe a 67-year-old woman with disseminated warts which she had had for more than 38 years. The lesions consisted of common and plane warts, wart-like plaques and red-brownish macules similar to those in pityriasis versicolor. Furthermore, during follow-up, several solar keratoses, plaques of Bowen's disease and invasive squamous cell carcinomas were excised. The patient also had T-cell immunodeficiency of unknown aetiology. Histopathology demonstrated that all the warts showed the cytopathological features of common warts, but not those of the warts in epidermodysplasia verruciformis (EV). We investigated the presence of human papillomavirus (HPV) DNA in the warts by blot hybridization and molecular cloning and found that the lesions harboured HPV 2, but not EV-HPVs or other HPVs. In addition, the histopathological distribution of the viral DNA was confirmed in paraffin sections of warts from the patient at different ages by in situ hybridization. However, these investigations yielded negative results in specimens of Bowen's disease and invasive squamous cell carcinoma. These results demonstrated that the patient had been infected with HPV 2 from childhood, but the negative results for detection of DNA of HPV 2 in carcinomas from the patient do not support an oncogenic potential for HPV 2. In conclusion, HPV 2, an aetiological agent of common warts in the general population, may induce a lifelong severe verrucosis in some immunosuppressed patients. PMID- 9990380 TI - Chronic endemic hydroarsenicism. AB - Chronic endemic hydroarsenicism in a 48-year-old man from Antofagasta, Chile, is reported. The literature on the global health problems of hydroarsenicism is reviewed, especially with regard to the carcinogenic action of arsenic. PMID- 9990379 TI - Heterogeneity of human papillomavirus DNA in a patient with Bowenoid papulosis that progressed to squamous cell carcinoma. AB - Bowenoid papulosis (BP) of the genitalia, characterized by the histological findings of a squamous cell carcinoma, follows a largely benign clinical course. The detection of oncogenic human papilloma viruses (HPV) from BP points to an aetiological role of these viral infections. A 47-year-old man with multiple genital skin lesions was seen over a 10-year period with the diagnosis of BP. Recently, he attended again with a recurrent genital tumour that was diagnosed as squamous cell carcinoma. His genital lesions progressed and became polymorphic in appearance, from a wart-like tumour to a reddish invasive plaque. To screen for the presence of different HPV sequences from different skin lesions and to correlate each HPV type with distinct clinical manifestations, polymerase chain reaction and single-strand conformational polymorphism (PCR-SSCP) were performed. PCR-SSCP revealed the presence of several types of HPV from different genital lesions. Sequencing results disclosed that he had a mixed infection of HPV6b, HPV16, HPV18 and HPV33, respectively. Interestingly, the clinical findings were fairly well correlated with the oncogenic potential of HPV found from each lesion. PMID- 9990381 TI - Glomangiosarcoma of the hip: report of a highly aggressive tumour with widespread distant metastases. AB - Malignant glomus tumour is an extremely rare neoplasm, and only a few cases with local invasive or aggressive features have been described to date. We present a distinctive case of a malignant glomus tumor arising on the skin of the left hip of a 47-year-old woman. The primary tumour was small, with a maximum diameter of 1 cm, but 2 years after the tumour was excised, multiple lung and skin metastases appeared. Post-mortem examination also revealed widespread metastases in almost all of the visceral organs. Histological examination showed that the primary tumour was composed of a sheet-like proliferation of epithelioid round or short spindle cells surrounding small venules. In addition, there was a proliferation of long spindle cells with eosinophilic fibrillary cytoplasm, which mimicked a leiomyosarcoma. The tumour cells were intensely immunopositive for actin and vimentin but were negative for desmin. This is an exceptional case of malignant glomangiomyoma with widespread metastases, which represents a distinct variant of de novo glomangiosarcoma. PMID- 9990382 TI - Eosinophilic foreign body granuloma after multiple self-administered bee stings. AB - A bee sting can cause a foreign body granuloma of the skin, due to activated macrophages at the stinging site. A 52-year-old woman presented with a large doughnut-shaped ulcerative tumour on the left side of her face. A bean-sized facial papule had grown to a 4.0 x 3.9 x 1.1 cm mass after multiple bee stings induced by herself over a period of 1 year. Histology showed epidermal ulceration with granulomatous inflammatory cell infiltration of many eosinophils. No micro organisms or foreign bodies were identified. Intralesional triamcinolone acetonide was not effective, but an excellent outcome was obtained using carbon dioxide laser vaporization of the lesion. PMID- 9990383 TI - The molecular basis of glucocorticoid-induced skin atrophy: topical glucocorticoid apparently decreases both collagen synthesis and the corresponding collagen mRNA level in human skin in vivo. AB - The effects of topical betamethasone-17-valerate on collagen propeptide levels, collagen mRNA level, lysyl oxidase mRNA and matrix metalloproteinase (MMP)-1 and MMP-2 mRNA levels were studied in human skin. Three days' treatment of healthy skin with topical betamethasone caused a 70-80% decrease in type I and III collagen propeptides in suction blister fluid. A similar decrease was found in type I collagen mRNA when assayed by either slot-blot hybridization or a quantitative polymerase chain reaction method, indicating that the decrease in collagen synthesis after topical glucocorticoid treatment is apparently due to a decrease in corresponding mRNA. mRNA of lysyl oxidase, which is an important enzyme catalysing the cross-linking of collagen chains, and collagen-degrading enzyme MMP-1 and MMP-2 mRNAs were not decreased in the same skin samples. This suggests that in vivo, glucocorticoids modulate variably the genes involved in collagen synthesis and degradation. Our study provides a solid molecular basis for glucocorticoid-induced dermal atrophy, which results from the decrease in functional collagen mRNA in the skin. PMID- 9990384 TI - HLA genotype and increased risk of skin cancer. PMID- 9990385 TI - Mortality from malignant melanoma in Chile, 1986-95. PMID- 9990386 TI - Chronic actinic dermatitis occurring in young patients with atopic dermatitis. PMID- 9990387 TI - Photosensitivity and the Rothmund-Thomson syndrome. PMID- 9990388 TI - Papuloerythroderma associated with hepatocellular carcinoma. PMID- 9990389 TI - Amyopathic dermatomyositis: report of three cases. PMID- 9990390 TI - Multiple lipomatosis in a patient with familial atypical mole syndrome. PMID- 9990391 TI - Familial naevus sebaceous of Jadassohn. PMID- 9990392 TI - Congenital onychodysplasia of the index fingers in identical twins. PMID- 9990393 TI - Gianotti-Crosti syndrome after measles, mumps and rubella vaccination. PMID- 9990394 TI - Botulinum toxin for focal hyperhidrosis: technical considerations and improvements in application. PMID- 9990395 TI - Leg ulcer associated with hydroxyurea treatment in a patient with chronic myelogenous leukaemia: successful treatment with prostagladin E1 and pentoxifylline. PMID- 9990396 TI - Severe, refractory epidermolysis bullosa acquisita complicated by an oesophageal stricture responding to intravenous immune globulin. PMID- 9990397 TI - Severe bullous drug reactions treated successfully with cyclophosphamide. PMID- 9990398 TI - Bullous fixed drug eruption due to paracetamol with an unusual immunofluorescence pattern. PMID- 9990399 TI - Pseudoporphyria induced by mefenamic acid. PMID- 9990400 TI - Terbinafine-induced subacute cutaneous lupus erythematosus. PMID- 9990401 TI - Exacerbation of systemic lupus erythematosus induced by terbinafine. PMID- 9990402 TI - Onychomycosis caused by infection with Paecilomyces lilacinus. PMID- 9990403 TI - A solitary collagenoma presenting in the labium majus. PMID- 9990404 TI - Focal facial dermal dysplasia with a hair collar. PMID- 9990405 TI - Bacteria and the skin: clinical practice and therapy update. AB - Any doctor using antibiotics should be aware of the increasing worldwide problem with multiresistant bacteria, with the majority of hospital-based infections in some countries being caused by these bacteria. Proper use of antibiotics is therefore mandatory for any physician, including for dermatologists, who treat bacterial infections of the skin. Detailed knowledge is needed of when to use topical versus systemic antibiotics, and for how long such treatments should be given. Besides the clinical symptoms of bacterial infections and treatment guidelines, an increased awareness has focused on the possible importance of bacterial toxins, including superantigens, and their contribution to skin inflammation. Rare syndromes such as Kawasaki's syndrome, toxic epidermal necrolysis or staphylococcal scalded skin syndrome, are well-known diseases elicited by specific bacterial toxins. But many observations give indirect support to the notion that bacteriae can augment the immune inflammation seen in common and important diseases such as psoriasis and atopic dermatitis. This supplement provides up-to-date information about skin bacteriology, information on the possible importance of superantigens for chronic skin diseases, and practical guidelines for the use of both topical and systemic antibiotic therapy, together with a review of the dangers following improper use. This information is important for all doctors, including dermatologists. PMID- 9990406 TI - Resistance to antibiotics used in dermatological practice. AB - The increased prevalence of bacterial resistance is one of the major problems of medicine today. Antibiotic resistance can be defined as the situation where the minimal inhibitory concentration is greater than the concentration obtainable in vivo. Resistance genes are easily transferred among bacteria, especially bacteria on skin and mucous membranes. In dermatological patients the most important resistance problems are found among staphylococci, Propionibacterium acnes and, to some extent, streptococci. Staphylococcus aureus strains have developed worldwide resistance to penicillin due to betalactamase production in > 90% of cases, and methicillin resistance is now a major problem with resistance levels of > 50% in certain areas of the world. These resistant strains are often multiresistant, and include resistance to erythromycin and tetracycline, with resistance to quinolone developing rapidly. Group A streptococci are still susceptible to penicillin, but increasing problems with erythromycin and tetracycline have been reported. After treatment with both systemic and oral antibiotics, P. acnes develops resistance in more than 50% of cases, and it is estimated that one in four acne patients harbours strains resistant to tetracycline, erythromycin, and clindamycin. To limit the development of antibiotic resistance, it is necessary to establish an antibiotic policy (prescription rules, reimbursement strategy, development of both national and local guidelines, and limitations on non-medical use). Clinicians also need access to rapid diagnostic methods, including resistance testing. This may provide further data for surveillance systems, reporting both antibiotic consumption and resistance levels. The involvement of clinical doctors in teaching and research in this area is probably the most important aspect, along with their involvement in the formulation of national and local guidelines. In the future we may consider it more important to ensure that future patients can be offered antibiotic treatment, rather than focusing on the patient presenting today. PMID- 9990407 TI - Skin bacteriology and the role of Staphylococcus aureus in infection. AB - Many of the staphylococci and coryneforms that inhabit normal human skin do not cause skin disease. Amongst the remainder the mechanisms of pathogenicity vary widely. For Proteus, Pseudomonas and Brevibacterium species proteolysis is a major determinant. The precise role of Corynebacterium minutissimum in erythrasma and the propionibacteria in acne is not known. Staphylococcus aureus, however, produces a wide range of non-specific agents, such as haemolysins and leucocidins as well as highly specific toxins such as the epidermolytic toxins involved in bullous impetigo and scalded skin syndrome. Most of the current attention, however, is devoted to the role of the enterotoxins and toxic shock toxin as superantigens, with emphasis on their role in atopic dermatitis. Molecularly similar toxins in the streptococci play a similar role and may also have a role in the aetiology of psoriasis. PMID- 9990408 TI - Staphylococcus aureus colonization in atopic dermatitis and its therapeutic implications. AB - Skin colonization with Staphylococcus aureus is a characteristic feature of atopic dermatitis with more than 90% of patients being colonized. Extracellular matrix proteins are important for the adherence of S. aureus to human keratinocytes. The bacterium interferes in the inflammatory process of atopic dermatitis in various ways, among which the ability to release superantigens in a high percentage of clinical isolates is of great importance. As the colonization correlates significantly with the severity of eczema, anti-staphylococcal treatment measurements are widely used. In cases of atopic dermatitis exacerbation with wide-spread weeping lesions, a systemic antibiotic treatment is warranted, with erythromycin no longer being recommended due to an increased resistance rate. In localized superinfected lesions the topical application of an antibiotic-glucocorticoid preparation may offer advantages to the mere steroid application. Based on efficacy and resistance data, fusidic acid is the antibiotic of choice. There is evidence that phototherapy in atopic dermatitis may be even more effective when combined with anti-staphylococcal measurements. In the future new therapeutical options may be available. PMID- 9990409 TI - The role of superantigens in human diseases: therapeutic implications for the treatment of skin diseases. AB - Although it is well established that immune mechanisms contribute to the pathogenesis of chronic inflammatory skin diseases such as atopic dermatitis (AD) and psoriasis, the actual events that trigger the immunological pathways resulting in these skin diseases are not well understood. Colonization and infection with Staphylococcus aureus and streptococci has been reported to exacerbate AD and psoriasis. Recent studies demonstrating that bacterial toxins can act as superantigens provide mechanism(s) by which S. aureus and streptococci could mediate an inflammatory skin lesion that consists predominantly of activated T-cells and monocytes. This review will explore the diverse mechanisms by which bacterial superantigens can induce skin inflammation following systemic or local infection. These observations provide a new direction for the development of novel approaches for the treatment of skin inflammation. PMID- 9990410 TI - The clinician's choice of antibiotics in the treatment of bacterial skin infection. AB - The development of modern antibiotics has vastly improved the therapy of cutaneous bacterial infections, particularly those caused by Staphylococcus aureus. This organism and beta-haemolytic streptococci are the most common cutaneous pathogens. A growing body of evidence suggests that proteins from S. aureus and some strains of streptococci can act as superantigens and cause polyclonal T-cell activation by binding directly to antigen-presenting cells. This process is a likely explanation of Kawasaki's syndrome as well as staphylococcal and streptococcal toxic shock syndrome. Sudden aggravation of atopic dermatitis, contact dermatitis and some cases of psoriasis can be similarly explained. Bacterial toxins can precipitate the staphylococcal scalded skin syndrome. Specific and effective eradication of bacteria and programmes to prevent recurrences are important, particularly in immune suppressed persons. Topical antibiotics used primarily for superficial infections of limited extent and for the prevention of recurrences in carriers of S. aureus should be combined with the use of topical disinfectants. The treatment of selected bacterial skin infections based on clinical examples will be discussed. These include secondarily infected dermatoses, cellulitis and streptococcal carriage in the ano genital region and staphylococcal folliculitis and nasal carriage. PMID- 9990411 TI - Fusidic acid in dermatology. AB - Fusidic acid is an antibiotic that belongs to a group of its own, the fusidanes. The molecule has a steroid-like structure but does not possess any steroid activity. The structure is thought to be responsible for the steroid-like high penetration, and for the fact that no cross-resistance or cross-allergy has been seen with other antibiotics in routine clinical use. The anti-microbial activity of fusidic acid is specifically aimed at the most common skin pathogens, including Staphylococcus aureus, towards which it is one of the most potent antibiotics. The place of fusidic acid in dermatology is in the treatment of mild to moderately severe skin and soft-tissue infections, e.g. impetigo, folicullitis, erythrasma, furunculosis, abscesses and infected traumatic wounds, whereas it is of less use in conditions such as hidradenitis suppurativa, chronic leg ulcers, burns and pressure sores. The topical combinations of fusidic acid with either betamethasone or hydrocortisone are extremely useful in the treatment of atopic dermatitis/eczema whenever staphylococcal/secondary infection is suspected, and in more persistent cases of eczema where staphylococcal superantigen may be playing an important exacerbating role. PMID- 9990412 TI - A new topical retinoid--why a new topical acne therapy? PMID- 9990413 TI - Pharmacology of adapalene. AB - Adapalene, a synthetic retinoid, is a new drug proposed for the treatment of acne patients. Studies on the in vitro and in vivo pharmacology of adapalene have shown that it is very active on cell and tissue proliferation and differentiation. Furthermore, adapalene has anti-inflammatory potential as determined by its anti-AP1 activity. Adapalene interacts selectively with the nuclear receptors RAR beta and RAR gamma, and its activity on proliferation and differentiation can be blocked by a RAR beta-gamma antagonist. Because RAR beta is not expressed in human keratinocytes, the effect of adapalene on the major cell type of the epidermis is certainly mediated by its interaction with RAR gamma. The unique pharmacological properties of adapalene may explain why, when compared to tretinoin, it has an improved therapeutic ratio due to its better tolerance. PMID- 9990414 TI - Chemical stability of adapalene and tretinoin when combined with benzoyl peroxide in presence and in absence of visible light and ultraviolet radiation. AB - Adapalene and tretinoin are molecules used in the topical treatment of acne vulgaris. Commercial formulations (adapalene 0.1% gel and tretinoin 0.025% gel) were mixed with equal volumes of commercially available benzoyl peroxide formulation (10% lotion) and subsequently exposed to light over 24 h. With and without exposition to light, adapalene exhibits a remarkable stability whereas tretinoin is very sensitive to light and oxidation. The combination of benzoyl peroxide and light results in more than 50% degradation of tretinoin in about 2 h and 95% in 24 h. PMID- 9990415 TI - Adapalene 0.1% gel and adapalene 0.1% cream stimulate retinoic acid receptor mediated gene transcription without significant irritative effects in the skin of healthy human volunteers. AB - A randomized, investigator masked, intra individual comparative study was conducted in 30 healthy volunteers to compare the cutaneous effects of adapalene 0.1% gel and adapalene 0.1% cream with their respective vehicles, using tretinoin 0.05% cream (n = 21) or tretinoin 0.1% cream (n = 9) and a tretinoin cream vehicle (n = 30) as controls. The products were applied to hip/buttock skin for 4 days under occlusive conditions. Cytosolic retinoic acid binding protein-II (CRABP-II) mRNA levels were measured using the RT-PCR technique in punch biopsies taken from 10 subjects. Epidermal thickness was assessed using image analysis of haematoxylin and eosin stained sections from another 11 subjects. Erythema was assessed in all subjects both by a visual scoring system and by chromameter. Adapalene 0.1% gel and adapalene 0.1% cream produced similar significant increases in CRABP-II mRNA levels compared to their vehicles (P < 0.01). The two tretinoin formulations also resulted in similar significant increases in CRABP-II compared to the cream vehicle (P < 0.001). However, only the two tretinoin formulations resulted in an increase in epidermal thickness and only the tretinoin 0.1% cream resulted in significant erythema. Adapalene 0.1% gel and adapalene 0.1% cream induce RAR-mediated gene expression to a similar degree in this model, without the irritant effects of tretinoin. PMID- 9990416 TI - Adapalene 0.1% gel for the treatment of acne vulgaris: its superiority compared to tretinoin 0.025% cream in skin tolerance and patient preference. AB - One hundred patients with acne vulgaris applied adapalene (Differin) 0.1% gel to one side of their face and tretinoin 0.025% cream to the other once a day for 4 weeks; the side of application was determined by randomization code. Patient tolerance (assessed as the side of the face least irritated by drug application) was recorded weekly and patient preference (assessed as the preparation more easily spread, absorbed more quickly, smelled better, felt best on the skin and least greasy to the feel) at completion of the study. The investigator measured skin irritation weekly, scoring erythema, skin dryness, desquamation and burning/stinging on a 10-point scale. After each week of treatment, 64-68% of patients found adapalene 0.1% gel more tolerable than tretinoin 0.025% cream (P < 0.05). At study completion, 65% of patients preferred adapalene 0.1% gel over tretinoin 0.025% cream (P = 0.003). An overall assessment showed adapalene 0.1% gel was significantly less irritating to the skin in terms of producing erythema, dryness, desquamation and burning/stinging, at Visits 2, 3 and 4 (P < 0.02). Thirty-two patients experienced mild to moderately severe adverse events; three had adverse events considered to be drug related (two with skin discomfort; one with skin dryness). One patient stopped using the study drugs because of dry skin. This study showed that a majority of patients preferred adapalene 0.1% gel over tretinoin 0.025% cream and that it caused significantly less skin irritation. PMID- 9990417 TI - Adapalene 0.1% gel has low skin irritation potential even when applied immediately after washing. AB - The purpose of this study was to evaluate the difference, if any, in facial skin tolerance of adapalene 0.1% gel applied immediately after washing, compared to delayed application as recommended for the other topical retinoids: tretinoin and isotretinoin. Twenty-five acne patients with mild to moderate acne vulgaris were included in this intra individual randomized comparison study where adapalene 0.1% gel was applied immediately after washing on one half of the face and 20-30 min after washing on the contralateral half-face, for 22 consecutive days. No difference between the two regimens was detected by the investigator or by 21 of the 22 patients who completed the study. It was concluded that application of adapalene gel 0.1% is well tolerated even when applied immediately after washing. PMID- 9990418 TI - Evaluation of clinical efficacy and safety of adapalene 0.1% gel versus tretinoin 0.025% gel in the treatment of acne vulgaris, with particular reference to the onset of action and impact on quality of life. AB - A randomized, multicentre, investigator-masked study was conducted in 105 patients with mild to moderate acne vulgaris to compare the efficacy and safety of adapalene 0.1% gel with tretinoin 0.025% gel after three months of treatment, with particular emphasis on reduction in inflammatory lesion counts after one week of treatment and impact on quality of life. In terms of efficacy, adapalene gel was found to be superior to tretinoin gel after one week of treatment, with respect to reduction in inflammatory lesion counts (32% vs. 17%, respectively; P = 0.001), total lesion counts (28% vs. 22%, respectively; P = 0.042) and global severity grade (28% vs. 16%, respectively; P = 0.001). No significant difference between the two treatments was found after 12 weeks of treatment for any of these variables. Evaluation of facial skin tolerance parameters showed significant differences between the two treatments in favour of adapalene for dryness, erythema, immediate and persistent burning and pruritus for at least one time point. One patient in the adapalene group and three patients in the tretinoin group experienced medical events which lead to discontinuation of treatment (skin irritation; NS). Quality of life scores improved more rapidly in the adapalene group than in the tretinoin group, with significant differences (P < 0.05) appearing at week 1 for questions related to problems with partners, close friends or relatives and to skin symptoms. There was also a significantly greater improvement in social and leisure activity in the adapalene group at week 12. Adapalene 0.1% gel reduced inflammatory and total lesion counts more rapidly than tretinoin 0.025% gel, and was also better tolerated. These differences appear to result in an earlier and greater quality of life improvement for the patients receiving adapalene. PMID- 9990419 TI - Comparative tolerance of adapalene 0.1% gel and six different tretinoin formulations. AB - Adapalene 0.1% gel (Differin gel) is a recently introduced topical treatment for mild to moderate acne which has been demonstrated to be much better tolerated and at least as effective as tretinoin 0.025% gel. We compared the tolerance of adapalene 0.1% gel with six different formulations and concentrations of tretinoin. A total of 55 healthy human subjects were enrolled in two controlled, randomized, observer blinded, intraindividual comparison studies. In the first study, adapalene 0.1% gel was evaluated for its 21-day cumulative irritation potential compared with tretinoin 0.025%, 0.05% and 0.1% cream, tretinoin 0.01% and 0.025% gel, and petrolatum (control). In the second study, adapalene 0.1% gel was evaluated for its 21-day cumulative irritation potential compared with tretinoin 0.025%, 0.05% and 0.1% cream, tretinoin 0.1% gel microsphere, and petrolatum (control). In both studies, cumulative irritation scores helped to define three groups of common irritancy potential, with significant differences between each group. In study A, the three groups were in descending order of irritancy: tretinoin 0.1% cream and tretinoin 0.05% cream; tretinoin 0.025% gel, tretinoin 0.01% gel and tretinoin 0.025% cream; adapalene 0.1% gel and petrolatum (control). In study B, the three groups were in descending order of irritancy: tretinoin 0.1% cream; tretinoin 0.05% cream, tretinoin 0.025% cream and tretinoin 0.1% gel microsphere; adapalene 0.1% gel and petrolatum (control). The experimental results show that adapalene 0.1% gel is significantly better tolerated than any of six formulations of tretinoin, including two gels, three creams and a microsphere formulation, ranging in potency from 0.01% to 0.1%. PMID- 9990420 TI - Comparison of adapalene 0.1% solution and tretinoin 0.025% gel in the topical treatment of acne vulgaris. AB - A multicentre study was conducted to compare clinical safety and efficacy of adapalene 0.1% solution and tretinoin 0.025% gel, both topical treatments for acne, in a once-daily dosage regimen for 12 weeks. A total of 297 patients were enrolled by eight investigators in this randomized, investigator-masked study in a parallel group design. An open label period using adapalene followed this study to assess the long-term safety of adapalene solution. Adapalene and tretinoin proved to be clinically and statistically effective in treating acne by reducing inflammatory (47% and 50%, respectively) and non-inflammatory lesions (57% and 54%) as compared to baseline. When comparing patients who had 75% or greater improvement in open comedones, adapalene was shown to be significantly more effective than tretinoin. No serious adverse event was reported during this study, including during the long-term period. The reactions that occurred were similar between treatments, i.e. burning, pruritus, scaling, dryness and erythema. PMID- 9990421 TI - A comparison of the efficacy and tolerability of adapalene 0.1% gel versus tretinoin 0.025% gel in patients with acne vulgaris: a meta-analysis of five randomized trials. AB - The purpose of this meta-analysis was to determine if adapalene 0.1% gel (Differin) provided superior efficacy and better tolerability than tretinoin 0.025% gel in the treatment of acne vulgaris. All comparative studies, both published and unpublished, from the United States and Europe, that fulfilled rigorous protocol criteria (multicentre, randomized, investigator-blind) were used. Five comparative studies met these criteria. In total, the meta-analysis evaluated 900 patients (450 treated with adapalene 0.1% gel, 450 treated with tretinoin 0.025% gel) with mild-to-moderate acne from the combined clinical trials. To avoid study bias, the meta-analysis used an intention-to-treat analysis. Statistical methodology for the meta-analysis included analysis of covariance, analysis of variance and Cochran-Mantel-Haenszel test. All statistical tests were two-sided, with the 0.05 probability level used to establish statistical significance, and 95% confidence intervals used to assess equivalence. Adapalene demonstrated equivalent efficacy to tretinoin in terms of reducing total lesion count. Adapalene demonstrated more rapid efficacy, as evidenced by a significant difference in the reduction of inflammatory and total lesions at week 1. Adapalene also demonstrated considerably greater local tolerability at all evaluation periods. The findings from this meta-analysis suggest that adapalene 0.1% gel constitutes a pharmacologic advance over such classic retinoids as tretinoin for the treatment of acne vulgaris. PMID- 9990422 TI - Expression of macrophage colony-stimulating factor, scavenger receptors, and macrophage proliferation in the pregnant mouse uterus. AB - During pregnancy, mouse uterine epithelial cells produce and secrete a large amount of macrophage colony-stimulating factor (M-CSF/CSF-1). Macrophages accumulate and proliferate in the undecidualized endometrium of the pregnant uterus. Observations showed that macrophages expressed scavenger receptor class A (type I and type II) and class C (macrosialin). Scavenger receptors appeared to be involved in the removal of apoptotic cells in the degenerated decidual tissue. The expression of class A and class C scavenger receptor mRNAs in the uterus of pregnant mice was elevated but the expression of class B scavenger receptor (CD36) mRNA was similar to that of non-pregnant mice. The expression of various cytokines and chemokines, including M-CSF, monocyte chemoattractant protein-1 (MCP-1) and macrophage inflammatory protein 1-alpha (MIP1-alpha), was enhanced in the uterus of pregnant mice, suggesting that these molecules regulate macrophage chemotaxis and immunological function in the uterus. These findings imply that the pregnant uterus provides a microenvironment for the recruitment, differentiation, and proliferation of macrophages and the regulation of scavenger receptor and cytokine expression for a successful pregnancy. PMID- 9990423 TI - An ultrastructural and immunohistochemical study of PC12 cells during apoptosis induced by serum deprivation with special reference to autophagy and lysosomal cathepsins. AB - In addition to the caspase family of proteinases, cathepsin D, a lysosomal aspartic proteinase, has been suggested to act as a proapoptotic mediator in mammalian cells. To further understand the roles of cathepsins B and D in apoptosis of the cells, we examined the precise alteration processes of ultrastructures and immunoreactivity for these enzymes in PC12 cells cultured under serum deprivation. Laser scanning microscopy showed immunoreactivity for cathepsins B and D to be finely distributed in the cytoplasm of PC12 cells at the onset of culture under serum deprivation. At 3 h after the onset of culture, the immunoreactivity for cathepsin B slightly decreased in the cells, while immunodeposits for cathepsin D in the cells became more intense and larger in size than those at 0 h. Positive staining for TUNEL in nuclei of the cells appeared at 6 h, though fewer in number. Corresponding to the increase in the number of TUNEL-positive cells at 12 h and 24 h, the immunoreactivity for cathepsin B was drastically diminished in the cells, whereas that for cathepsin D was significantly augmented, especially in TUNEL-positive cells. Electron microscopically, autophagic vacuoles/autolysosomes appeared in the cytoplasm of the cells 3 h after the onset of culture. A distinct nuclear change showing relatively condensed chromatin first appeared in the peripheral part of the nuclei at 6 h. The number of PC12 cells having nuclei with chromatin condensation increased especially at 24 h, while these cells showed shrinkage of both their cytoplasm and nuclei. Dense bodies and autophagic vacuoles with limiting membranes were seen in these cells. These results showing the occurrence of autophagy and imbalance of protein amounts between cathepsins B and D during apoptosis may argue for our hypothesis that these enzymes are, in part, involved in the cell death cascade for PC12 cells following serum deprivation. PMID- 9990424 TI - Stage-specific localization of basigin, a member of the immunoglobulin superfamily, during mouse spermatogenesis. AB - Ablation of the transmembrane glycoprotein basigin leads to azoospermic mice, indicating that this gene is essential for spermatogenesis. To examine the functions of basigin in the testis, the precise localization of basigin during spermatogenesis was examined immunohistochemically. In the adult mouse testis, basigin immunoreactivity appeared on the cell surface of leptotene spermatocytes and gradually increased in intensity during the meiotic prophase. Cytoplasmic staining, as well as cell surface staining, was detected in spermatids. The most conspicuous reactivity was found in the spermatids at steps 9-11 and in the flagella of spermatids. Immuno-electron microscopic analysis demonstrated that basigin was localized not only on the plasma membranes of spermatocytes and spermatids, but also on the plasma membrane of the Sertoli cell processes which contact the spermatocytes and spermatids. Basigin immunoreactivity was also detected during postnatal development in spermatocytes and spermatids but not in spermatogonia. Experimental cryptorchid testes which contain only spermatogonia and Sertoli cells in the seminiferous epithelium showed no basigin immunoreactivity. Seven days after surgical reversal of the cryptorchid testis, spermatocytes reappeared in the tubules, along with basigin immunoreactivity. Furthermore, in sterile mutant mice, in which neither spermatocytes nor spermatids were generated, no basigin immunoreactivity was detected in the seminiferous tubules. These findings indicate that expression of basigin is concomitant with appearance of spermatocytes in the seminiferous tubule, and suggest that basigin is involved in the interaction between Sertoli cells and germ cells at specific stages of spermatogenesis. PMID- 9990425 TI - Postnatal development of the rat sublingual glands. A morphometric and radioautographic study. AB - The postnatal development of rat sublingual glands was analyzed by morphometric and radioautographic studies. The absolute number of each cell type was evaluated by the Aherne II morphometric method for cell counting and labeling indices of these cell types were determined in radioautographs from animals injected with 3H thymidine. The quantitative cell population kinetic studies were accompanied by morphologic analysis of the modifications in each gland structure. The data concerning evolution of number of each cell type were submitted to analysis by least squares fit-exponential curve. The exponential equations duplication times for the acinar, serous demilune, intercalated duct, striated duct and stroma cells from 2 to 30 days of age were 7.5, 9.0, 10.8 and 9.5 days, respectively. On the other hand, the mean labeling indices for the same cell types during the same period were 9.5%, 5.8%, 7.2%, 3.3% and 4.3%, respectively. Thus, the intercalated duct cells exhibited the second highest labeling index and the slowest growth rate, while the striated duct cells showed the lowest labeling index and the third highest duplication time. The fact that the striated duct cell labeling index does not explain the relatively short duplication time of these cells, suggests that cells from other neighboring morphologic compartments, probably from intercalated duct, migrate and differentiate into striated ducts cells. PMID- 9990426 TI - Immunohistochemical localization of secretory immunoglobulins in the main excretory duct of the human submandibular gland. AB - The localization of IgA, IgG, and IgM was investigated immunohistochemically in the mucosal surface of the main excretory duct of the human submandibular gland in order to verify the possible antimicrobial properties of this duct. Only secretory IgA-immunoreactivity was recognized in the epithelial cells of the duct. An intense immunoreactivity was observed in the cytoplasm of some cells and at the luminal surface of most of the cells. Clusters of IgA-positive immuno competent cells were also recognizable in the subepithelial layers. No reactivity for IgG and IgM was noticed. The results suggest that the ductal epithelium may actively be involved in the release of secretory IgA, which could play a prominent role in the local defense mechanism of the duct. PMID- 9990427 TI - Spermatids of prepubertal male rats are susceptible to carbendazim during early spermiogenesis. AB - The fungicide carbendazim, a male reproductive system toxicant, affects the adult testis, while prepubertal animals are assumed to be unsusceptible to the chemical. The present study was conducted to re-evaluate the susceptibility of rat prepubertal testis (25-30 days old) to carbendazim based on the incidence of spermatid abnormalities, including nuclear enlargement (megaspermatids) and binucleate round spermatids. In control prepubertal rats treated orally with corn oil vehicle alone, seminiferous tubules containing magno- and/or binucleate round spermatids were often observed in the groups at stages II-III, IV-V and VI-VII. At 3.0 days after treatment with carbendazim (100 mg/kg), seminiferous tubules containing spermatids with identical abnormalities were significantly increased, including groups at all stages. Significant increases were also observed at stages IV-V and VI-VII at day 4.5, and VI-VII at day 7.5. In contrast, the frequency of spermatids with these abnormalities was reduced in the groups at stages II-III and IV-V at day 7.5. These findings confirm that the prepubertal rat testis is susceptible to carbendazim during early spermiogenesis. PMID- 9990428 TI - Structural organization of lymphatics in the monkey esophagus as revealed by enzyme-histochemistry. AB - The fine structure and distribution of lymphatic vessels in the monkey esophageal wall were studied by light and electron microscopy using an enzyme-histochemical method. Identification of lymphatics was made by 5'-nucleotidase staining, whereas blood vessels were visualized by alkaline phosphatase staining. This technique revealed intramural lymphatic networks in the mucosa, submucosa, and myenteric layer of the esophagus. The organization of lymphatics in the esophagus basically conformed to that of the small intestine, although they showed certain distribution patterns peculiar to the esophagus. The lamina propria mucosae exhibited a double-layered lymphatic network, and lymphatic capillaries extended into its papillae. Despite their forming blind ends and being closed by endothelial cells, the lymphatics in the mucosal papillae were found to contain lymphocytes in their lumen. This suggests that free cells might penetrate the endothelium to enter these initial portions of the lymphatics. PMID- 9990429 TI - Immunocytochemical demonstration of the synovial membrane in experimentally induced arthritis of the rat temporomandibular joint. AB - The present study is first to report an experimental model of adjuvant-induced arthritis in the rat temporomandibular joint (TMJ). Arthritis was induced by simultaneous intradermal administrations of Freund's complete adjuvant, one at the parietal scalp and the other at the base of the tail. In this model, we demonstrated responses of the synovial membrane by immunocytochemistry using antibodies to OX6 and ED1 which recognize Ia antigen in MHC class II antigen expressing cells and the macrophage/monocyte lineage, respectively. Three weeks after administration, no remarkable signs of inflammation were macroscopically recognizable in the TMJ, but microscopically the synovial membrane in the TMJ revealed marked changes such as enhanced vascularization and hemostasis in the sublining layer and a thickening in the synovial lining cell layer. Intense OX6 immuno-reactivity was found in the synovial lining cells at lesions in the experimental group but not in the control group. Immunoelectron microscopy revealed that these OX6-immunopositive synovial lining cells developed dense cytoplasmic processes and numerous vacuoles and vesicles, resembling type A cells. Part of the type A cells also showed ED1-immunoreactivity. The expression of OX6 or ED1 immunoreactivity in the synovial lining cells might be involved in the initial immune responses in this arthritis model because the synovial membranes are exposed to the synovial fluids which have been believed to contain antigenic substances. PMID- 9990430 TI - Amelogenin protein in tooth germs of the snake Elaphe quadrivirgata, immunohistochemistry, cloning and cDNA sequence. AB - In the snake, Elaphe quadrivirgata, the occurrence of amelogenin was immunohistochemically demonstrated in the enamel of developing tooth germs. Teeth of the snake are covered with a thin true enamel layer about 1-2 microns in thickness. Light and electron microscopic immunohistochemistry indicated an intense amelogenin immunoreactivity occurring in the enamel layer during the secretory stage of tooth development. Cloning and cDNA sequence of snake amelogenin was performed by RT-PCR. The amino acid sequence of the snake amelogenin cDNA--in its portion corresponding to the area from exon 5 to exon 7 of human X189 amelogenin gene--showed 45% homology with humans. Regions of both the N-terminus and C-terminus were well conserved. Furthermore, the positions of prolin in the amino acid alignment of the snake amelogenin corresponded well with those of human amelogenin. It is suggested that prolin is an essential constituent of amelogenin and therefore its positions in the molecule have been conserved after the evolutionary divergence of reptiles and mammals. This study using reptiles is the first detection of specific amelogenin immunoreactivity by high resolutional immunoelectron microscopy and the first cloning of amelogenin cDNA in a non-mammalian animal. PMID- 9990431 TI - Immunohistochemical localization of pleiotrophin and midkine in the lingual epithelium of the adult rat. AB - Distribution of two heparin-binding molecules, pleiotrophin (PTN) and midkine (MK), was investigated by immunohistochemistry in the lingual epithelium of the adult rat. In the lingual epithelium, both PTN- and MK-like immunoreactivities were observed in its basal cell layers, showing a mesh-like appearance. These molecules were also found along the surface of the taste bud cells; an intense immunoreaction was detected at the base of the taste buds in the circumvallate and foliate papillae. At the electron microscope level, the immunoreactive products were localized on the cell surface and basement membrane at the base of the taste buds. The immunoreactivity for PTN was distributed more diffusely than that for MK. It was suggested that these molecules may be involved in the differentiation and maintenance of taste bud cells, possible via their trophic effect upon approaching nerves. PMID- 9990432 TI - Neonatal temperament, maternal interaction, and the need for "alonetime". AB - In one of a set of studies exploring the need for time alone throughout development, infant temperamental characteristics, their relation to infant needs for time alone, and maternal perceptions of these needs are examined via videotapings of the infants' signals of disengagement and engagement. Descriptive data based on three mother-infant dyads suggest that infants clearly signal their needs for rest and disengagement in the first eight weeks, and develop unique patterns of "alonetime" behavior that may be related in part to temperamental differences. PMID- 9990433 TI - Long-term effects of internment during early childhood on third-generation Japanese Americans. AB - A national survey investigated the long-term effects of World War II internment on family communication, ethnic preference, confidence in personal rights, and attitudes to redress among third-generation Japanese Americans (sansei) who were infants or young children during incarceration. Findings were compared to those for noninterned sansei with and without parents who had been interned. Differences between interned and noninterned sansei were found primarily in family communication and family distance. PMID- 9990434 TI - Postpartum affect and depressive symptoms in mothers and fathers. AB - In a study of the postpartum affective experiences of couples, mothers and fathers completed questionnaires on coping, marital satisfaction, stress, positive and negative affect, and depression one month pre- and then one month postpartum. More than one-fourth of both mothers and fathers reported elevated depressive symptoms, which correlated significantly between parents. Prepartum coping, stress, and affect significantly predicted postpartum affect. Research and clinical applications of the findings are discussed. PMID- 9990435 TI - Anticipating parental death in families with young children. AB - Findings from a community study of parentally bereaved children demonstrate that forewarning of death is not associated with more favorable mental health outcomes than is sudden death of a parent. The applicability of the of the general anticipatory grief literature to the circumstances of children facing the loss of a parent is called into question, and the need to assess more carefully the effect on children of a parent's protracted terminal illness is emphasized. PMID- 9990436 TI - Early parental separation and the psychosocial development of daughters 6-9 years old. AB - The relationship of timing of early parental separation to psychosocial development of daughters was examined in 77 girls, 6-9 years of age over a four year period. Disruptive behavior across contexts was prevalent in girls separated between birth and two years of age. Girls separated between three and five years of age showed more externalizing behavior problems, but only in school. Results suggest that early parental separation has more pervasive and stable negative effects on psychosocial adjustment of girls in this age group in single-parent families. Implications of the findings and directions for research are discussed. PMID- 9990437 TI - Childhood stress and symptoms of drug dependence in adolescence and early adulthood: social phobia as a mediator. AB - Retrospective data from 7,871 individuals age 16 to 64 were used to investigate whether, among those diagnosed with lifetime social phobia, its symptoms serve to link life events and chronic strains in childhood with symptoms of drug dependence in adulthood. Findings suggest social phobia as a pathway through which early life events and chronic strains affect the development of drug related problems. Implications for research and clinical practice are discussed. PMID- 9990438 TI - Impact of environment on adolescent mental health and behavior: structural equation modeling. AB - This study uses structural equation models to describe how objective neighborhood, perceived neighborhood, and environmental support predict mental health; 792 adolescents responded to highly structured interviews. The effect of objective environment on mental health was mediated through its influence on perceived neighborhood. Environmental support mitigated negative perceptions of environment and the effect of perceived environment on mental health, while exposure to violence augmented the negative effect of perceived environment. PMID- 9990439 TI - Adult transracial and inracial adoptees: effects of race, gender, adoptive family structure, and placement history on adjustment outcomes. AB - Adjustment outcomes of 224 transracial and inracial adoptees were investigated using data collected over 17 years. Findings reveal an association between adoptees' outcomes and their race, gender, and adoptive family structure. Placement history was not significant. Implications for policy and practice are discussed, as are future directions for research. PMID- 9990440 TI - Predicting caregiver stress: an ecological perspective. AB - The family caregiving process for children with severe emotional disorders is conceptualized from an ecological perspective and examined in light of outcomes for caregivers. This study of 259 families assessed the relative importance, individually and in combination, of various clusters of caregiver, child, family, and environmental characteristics and responses as predictors of caregiver stress. Findings raise questions about current practice and policy, and suggest directions for future research. PMID- 9990441 TI - Perceptions of control and long-term recovery from rape. AB - The relationship between perceptions of control and symptoms of both long-term depression and post-traumatic stress was examined. Enduring beliefs of personal competence and control were found to be associated with lower rates of depression and stress and to be stronger predictors of long-term recovery than were rape specific attributions. Implications for clinical practice are discussed. PMID- 9990442 TI - "Patient was hit in the face by a fist..." a discourse analysis of male violence against women. AB - A discourse analysis of professional and popular literature describing male violence against women surveyed 165 abstracts and 11 full-length articles. The phrase "male violence" was used only eight times in these writings; male gender was infrequently mentioned, whereas female gender was often present in the identification of victims of male violence. Consequences of the absence of men as perpetrators and visibility of women in the literature on male violence against women are discussed, and change in these discursive practices is called for. PMID- 9990443 TI - Adoption of a sibling: reactions of biological children at different stages of development. AB - Responses of biological children to the adoption of a sibling during latency, adolescence, and young adulthood are described. Case vignettes are presented, underlying dynamics are discussed, and a framework for understanding children's behavior is suggested. Reactions of peer groups of latency-age children, and of biological adolescent children in a case of kinship adoption, are examined. PMID- 9990444 TI - Psychosocial stressors among sheltered homeless children: relationship to behavior problems and depressive symptoms. AB - Level of exposure to severe psychosocial stressors was assessed among homeless children in emergency family shelters in an urban locale. The relationship between such exposure and child mental health problems was then investigated, along with the effects of adult family social support. Implications of the findings are discussed. PMID- 9990445 TI - Fathers with severe mental illness: characteristics and comparisons. AB - Among patients with severe mental illness attending a large, urban, outpatient mental health clinic, fathers are described and compared with nonfathers and with mothers on demographic, clinical, and child-related characteristics, and on resources and service needs. While fathers and nonfathers with mental illness differed significantly on most variables, fathers and mothers with mental illness were remarkably similar except on child-related characteristics. Issues regarding fathers' experiences and service needs are discussed. PMID- 9990446 TI - Synthesis and evaluation of anthranilic acid-based transthyretin amyloid fibril inhibitors. AB - Eight small molecules were synthesized to evaluate the structure activity relationships (SAR) of N-substituted anthranilic acids. The molecules were synthesized by benzylation or arylation of methyl anthranilate. A light scattering-based amyloid fibril formation assay was used to evaluate potential inhibitors of transthyretin (TTR) amyloid fibril formation in vitro. The m carboxyphenylated and o-trifluoromethylphenylated anthranilic acids are potent inhibitors that will be subjected to further SAR and structural analysis. PMID- 9990447 TI - Synthesis and evaluation of potent and selective c-GMP phosphodiesterase inhibitors. AB - Syntheses and structure-activity relationships (SAR) of cGMP selective phosphodiesterase inhibitors are discussed. Potent and selective inhibitors are produced when the C-2 position of tetracyclic guanine 1 is substituted with alkyl chains containing six carbon atoms. PMID- 9990448 TI - Inhibition of transforming growth factor-beta 2 expression with phosphorothioate antisense oligonucleotides in U937 cells. AB - Four types of phosphorothioate antisense oligonucleotides for transforming growth factor-beta 2 were synthesized and tested for their antisense activity in U937 cells. The full-length phosphorothioate modified antisense analogues exhibited the highest inhibitory effects on the transforming growth factor-beta 2 expression in U937 cells. PMID- 9990449 TI - A study of novel antiallergic agents with eosinophilic infiltration inhibiting action. AB - The antiallergic action of a series of novel mono-O-substituted trimethylhydroquinones was investigated. Among this series of the compounds, 4-[4 [4-(diphenylmethyl)-1-piperazinyl]butoxy]-2,3,6- trimethylphenol (compound 3) showed a potent antihistaminic action (pA2 = 7.11) and an antiasthmatic action (100 mg/kg. p.o) on sensitized guinea pigs. Moreover, this compound exhibited a strong eosinophilic infiltration inhibiting action on sensitized mice (100 mg/kg p.o.). PMID- 9990450 TI - Synthesis and methemoglobin toxicity of the amides of 6/7 mono or disubstituted quinolone. AB - A series of 6/7-mono and disubstituted quinolone-3-carboxamide derivatives (1-12) were synthesized and their in vitro methemoglobin producing capacity have been delineated. The compounds 5, 6, 9 and 10 showed minimum methemoglobin toxicity. PMID- 9990451 TI - New minimal substrate structural requirements in the enzymatic peroxidation of alkenes with soybean lipoxygenase. AB - A carboxylic or a charged head group in fatty acid analogs is not an essential structural requirement for binding and catalysis in soybean lipoxygenase-1 catalyzed oxidations. PMID- 9990452 TI - Chemical and enzymatic synthesis of glycoconjugates. 5: One-pot regioselective synthesis of bioactive galactobiosides using a CLONEZYME thermophilic glycosidase library. AB - Enzymatic synthesis of galactobiosides using a versatile CLONEZYME thermostable glycosidase library was studied. One-pot transglycosylation reactions were demonstrated to synthesize beta(1-->4), beta(1-->6), and alpha(1-->6) disaccharide sequences with high regioselectivity and moderate to high yields. PMID- 9990453 TI - Design and synthesis of 6-(6-D-ribitylamino-2,4-dihydroxypyrimidin-5-yl)-1-hexyl phosphonic acid, a potent inhibitor of lumazine synthase. AB - A novel inhibitor of lumazine synthase, the penultimate enzyme in the biosynthesis of riboflavin, has been synthesized. The inhibitor was designed by computer graphics molecular modeling using a hypothetical structure of the enzyme inhibitor complex. The new compound is relatively potent when compared with the known inhibitors, and displays a KI of 109 microM. PMID- 9990454 TI - Highly constrained dipeptoid analogues containing a type II' beta-turn mimic as novel and selective CCK-A receptor ligands. AB - Conformationally constrained dipeptoid analogues containing the type II' beta turn mimic (2S,5s,11bR)-2-amino-3-oxohexahydroindolizino[8,7-b]indole-5 carboxylate framework in place of the alpha-MeTrp residue, show high binding affinity and selectivity for CCK-A receptors, suggesting that a turn-like conformation could contribute to the bioactive conformation at this CCK receptor subtype. PMID- 9990455 TI - Toxicity and osmoprotective activities of analogues of glycine betaine obtained by solid phase organic synthesis towards Sinorhizobium meliloti. AB - Seven analogues of the bacterial osmoprotectant glycine betaine (GB, trimethylammonioacetate), in which the methyl groups of the Me3N+ moiety are replaced by various substituents, were obtained by SPOS using Wang resin. Their biological activities (osmoprotection vs toxicity), appeared closely related to their uptake efficiency and their catabolism in the betaine-demethylating model bacterium Sinorhizobium meliloti. PMID- 9990456 TI - Platelet glycoprotein IIb/IIIa receptor antagonists derived from isoxazolidines. AB - A series of isoxazolidines has been synthesized as mimetics of the RGD sequence and was evaluated as antagonists of the platelet glycoprotein IIb/IIIa receptor. These compounds were shown to be highly potent GPIIb/IIIa antagonists, exhibiting submicromolar potencies. PMID- 9990457 TI - Monoacetyldiglycerides as new Ca2+ mobilizing agents in rat pancreatic acinar cells. AB - Several monoacetyldiglycerides were synthesized from glycerol in search for new Ca2+ mobilizing agent in vitro. All monoacetyldiglycerides except linolenoyl and phenlycyclopropylcarbonyl derivatives showed activity toward Ca2+ release in pancreatic acinar cells. Linoleoyl and docosahexaenoyl derivatives were chosen for further test and exhibited unique activity. PMID- 9990458 TI - Stereospecificity of hydrogen transfer by the NAD(+)-linked alcohol dehydrogenase from the Antarctic psychrophile Moraxella sp. TAE123. AB - Investigation of the stereochemistry of the hydride transfer in reactions catalyzed by the recently isolated NAD(+)-linked alcohol dehydrogenase from the Antarctic psychrophile Moraxella sp. TAE123 was accomplished by using 1H NMR spectroscopy of the deuterated coenzyme. It was found that this new psychrophilic enzyme is a type A dehydrogenase. Moraxella sp. ADH reduces stereospecifically 2 butanone to produce (S)-2-butanol. PMID- 9990459 TI - Synthesis and biological evaluation of novel cryptophycin analogs with modification in the beta-alanine region. AB - Structure modification of the beta-alanine region (fragment C) of the potent antimitotic agent cryptophycin was investigated. This includes: (1) introduction of substituents at the previously unsubstituted C7 position of the macrolide ring and (2) replacement of the (2R)-3-amino-2-methyl-propanoic acid (beta-alanine) with various (1)-amino acids to give the corresponding 15-membered unnatural cryptophycin analogs. PMID- 9990460 TI - The synthesis and biological activity of a series of 2,4-diaminopyrido[2,3 d]pyrimidine based antifolates as antineoplastic and antiarthritic agents. AB - A new series of 2,4-diaminopyrido[2,3-d]pyrimidine based antifolates 1-3 were synthesized through an efficient conversion of 2-pivaloyl-4-oxo-6 ethynylpyrido[2,3-d]pyrimidine 5 to the corresponding 4-amino analog 7 via the activated 1,2,4-triazole intermediate 6. Compound 7 was used as the key intermediate for the preparation of the final products. The detailed biological evaluation of these compounds both as antineoplastic and antiarthritic agents will be discussed. PMID- 9990461 TI - Artificial metalloenzymes based on protein cavities: exploring the effect of altering the metal ligand attachment position by site directed mutagenesis. AB - In an effort to construct catalysts with enzyme-like properties, we are employing a small, cavity-containing protein as a scaffold for the attachment of catalytic groups. In earlier work we demonstrated that a phenanthroline ligand could be introduced into the cavity of the protein ALBP and used to catalyze ester hydrolysis. To examine the effect of positioning the phenanthroline catalyst at different locations within the protein cavity, three new constructs--Phen60, Phen72 and Phen104--were prepared. Each new conjugate was characterized by UV/vis spectroscopy, fluorescence spectroscopy, guanidine hydrochloride denaturation, gel filtration chromatography, and CD spectroscopy to confirm the preparation of the desired construct. Analysis of reactions containing Ala-OiPr showed that Phen60 catalyzed ester hydrolysis with less selectivity than ALBP-Phen while Phen72 promoted this same reaction with higher selectivity. Reactions with Tyr OMe were catalyzed with higher selectivity by Phen60 and more rapidly by Phen104. These results demonstrate that both the rates and selectivities of hydrolysis reactions catalyzed by these constructs are dependent on the precise site of attachment of the metal ligand within the protein cavity. PMID- 9990462 TI - Synthesis and biological activity of KCB-328 and its analogues: novel class III antiarrhythmic agents with little reverse frequency dependence. AB - A series of 3,4-dimethoxyphenethylamine derivatives was prepared, and their prolongation effects on effective refractory period of contractile response (ERPc) and action potential duration (APD) in isolated guinea-pig papillary muscles at 1 Hz and 3 Hz were examined. SAR studies led to the identification of KCB-328 (51) which is a novel class III antiarrhythmic agent with little reverse frequency dependence. PMID- 9990463 TI - 2,6,9-trisubstituted purines: optimization towards highly potent and selective CDK1 inhibitors. AB - Novel 2,6,9-substituted purine derivatives represent a class of potent and selective inhibitors of CDK1/cyclinB. The synthesis, SAR and biological profile of selected compounds are described. PMID- 9990464 TI - Azaindole derivatives with high affinity for the dopamine D4 receptor: synthesis, ligand binding studies and comparison of molecular electrostatic potential maps. AB - Piperazinylmethyl substituted pyrazolo[1,5-a]pyridines and related heterocycles were synthesized and found to recognize selectively the dopamine D4 receptor. For the most potent derivative 10d a Ki value of 2.0 nM was observed. SAR studies including the comparison of molecular isopotential surfaces were performed. PMID- 9990465 TI - Design and synthesis of simplified sordaricin derivatives as inhibitors of fungal protein synthesis. AB - A reduction of the tetracyclic skeleton of sordarins and sordaricins to a cyclopentane ring bearing the pharmacophore functional groups led to new derivatives retaining part of their in vitro and whole-cell activity. PMID- 9990466 TI - Cleavage of L-leucine-containing dipeptides by Clostridium butyricum. AB - The ability of Clostridium butyricum cultures to hydrolyze three L-leucine containing dipeptides (Leu-Leu, Leu-Gly and Gly-Leu) in a synthetic minimal medium is demonstrated by using gas chromatography coupled with mass spectrometry. The 13C nuclear magnetic resonance and a labeled dipeptide L-[1 13C]Leu-Gly were used to confirm this activity. PMID- 9990467 TI - Prodrugs for targeting hypoxic tissues: regiospecific elimination of aspirin from reduced indolequinones. AB - A series of regioisomeric derivatives of a 1-methylindole-4,7-dione were synthesised, substituted with a 2-acetoxybenzoate leaving group linked through the (indol-2-yl)methyl or (indol-3-yl)methyl (or propenyl) positions. Reductive elimination of the leaving group occurred from the (indol-3-yl)methyl derivatives but not the 2-substituted regioisomers, indicating that only the C-3 position may be utilised in bioreductively-activated drug delivery, which was demonstrated with an aspirin prodrug. PMID- 9990468 TI - The detection of positive blood cultures by the AccuMed ESP-384 system: the clinical significance of three-day testing. AB - A total of 805 positive blood cultures obtained over a 4-month period during 1997 by the AccuMed ESP-384 system were evaluated and compared with 471 positive blood cultures obtained during 1989. Of the 805 microorganisms isolated in 5-day culture and testing by the ESP-384, 671 (83.4%) were detected within the first 2 days and 758 (94.2%) within 3 days. There were 47 (5.7%) microorganisms detected in culture Days 4 and 5 from 42 patients and review of the medical records from these patients demonstrated that no significant changes in clinical management were instituted as a result of detection and identification of these isolates. These 47 organisms were considered to be zero to equivocal clinical relevance. These data suggest that a 3-day routine blood culture incubation protocol with the ESP-384 system may be sufficient when considering detection rate, clinical relevance, and cost-effectiveness. The microbial spectrum and relative frequencies in this study were found to be similar to those of positive blood cultures obtained during 1989. PMID- 9990469 TI - In vitro susceptibilities of Aspergillus species to voriconazole, itraconazole, and amphotericin B. AB - We studied the in vitro activity of voriconazole (VCZ) itraconazole (ITZ) and amphotericin B (AMB) against 216 clinical isolates of Aspergillus spp. (142 Aspergillus fumigatus and 74 nonfumigatus Aspergillus spp. isolates) using a broth macrodilution method. The MICs (microgram/mL) (mean, range) for A. fumigatus were: VCZ 0.88, 0.25-4; ITZ 0.54, 0.25-4; AMB 2.16, 0.5-8. MIC90s were: VCZ 2, ITZ 1, AMB 4. MICs for nonfumigatus Aspergillus spp. were: VCZ 1.57, 0.25 4; ITZ 1.74, 0.25-4; AMB 2.88, 0.5-8. MIC90s for this group were: VCZ 4, ITZ 4, AMB 4. We also studied the susceptibility to VCZ of 18 AMB-resistant (mean, MIC 6.0 micrograms/mL) and 28 ITZ-resistant (mean, MIC 13.28 micrograms/mL) A. fumigatus isolates selected in the laboratory. The mean MICs of VCZ were 0.59 microgram/mL for AMB-resistant and 1.32 micrograms/mL for ITZ-resistant isolates. Our study showed that VCZ and ITZ had comparable in vitro activity against the isolates studied, except against A. fumigatus, where the MIC of ITZ was lower. The azoles had better in vitro activity than AMB against A. fumigatus and non fumigatus spp. The non-fumigatus Aspergillus spp. were less susceptible to all three antifungals evaluated. When tested against ITZ- or AMB-resistant A. fumigatus strains, VCZ retained good activity, showing only a modest rise in the MIC against ITZ-resistant strains. PMID- 9990470 TI - IS6110 dot blot hybridization for the identification of Mycobacterium tuberculosis complex. AB - To explore a simple, rapid, and inexpensive way to identify Mycobacterium tuberculosis complex culture, dot blot hybridization using IS6110 as the marker was performed against 2788 known clinical isolates of mycobacteria including M. tuberculosis (n = 721), M. kansasii (177), M. marinum (10), M. avium complex (700), M. terrae complex (203), M. fortuitum (476), M. chelonae (439), and other nonpigmented Runyon's Group IV mycobacteria (62). We found that the sensitivity and specificity of the test were 94.3% and 100%, respectively. When this method was evaluated in a laboratory blind study of 1253 initially unknown clinical isolates, its sensitivity and specificity were 91.2% and 100%, respectively. Because this identification test is technically simple, rapid, and can be done in batches, together with its high sensitivity and specificity, it is a cost effective method for routine identification of M. tuberculosis complex in laboratories of areas with a high incidence of tuberculosis. PMID- 9990471 TI - Antimicrobial activity of SCH27899 (Ziracin), a novel everninomicin derivative, tested against Streptococcus spp.: disk diffusion/etest method evaluations and quality control guidelines. The Quality Control Study Group. AB - To combat the increasing rates of penicillin resistance among pneumococci and viridans group streptococci, new Gram-positive active agents are needed to avoid the overuse of vancomycin. SCH27899 is an everninomicin derivative with strong activity against glycopeptide-resistant enterococci, oxacillin-resistant staphylococci, and penicillin-resistant streptococci. This study tests the in vitro activity of SCH27899 against 304 strains of streptococci and evaluates the quality of the agar dilution, broth microdilution, disk diffusion, and Etest methods for this antimicrobial agent. Quality-control (QC) ranges for SCH27899 are also proposed. SCH27899 broth microdilution MICs among the penicillin susceptible and -resistant streptococci tested ranged from < or = 0.008-0.5 microgram/mL. Organism groups with their respective MIC90s were as follows: Streptococcus pneumoniae (100 strains) and beta-haemolytic streptococci (70 strains), 0.12 microgram/mL; Streptococcus bovis (10 strains), 0.25 microgram/mL; and viridans group streptococci (124 strains), 0.5 microgram/mL. Etest SCH27899 MICs correlated well with broth microdilution MICs (92% +/- one log2 dilution, 98% +/- two log2 dilutions). Agar dilution SCH27899 MICs correlated well with broth microdilution MICs, but a shift toward slightly higher agar dilution MICs was attributed to difficulties in reading trailing endpoints with this method. Three concentrations (2.5, 5, and 10 micrograms) of SCH27899 were used for the disk diffusion method with small inhibition zone diameters (range, 11 to 19 mm) and limited variation between diameters (+/- 2 mm) as a result, both products of this compound's high molecular weight and poor diffusion through agar mediums. Proposed control ranges for SCH27899 when testing S. pneumoniae ATCC 49619 from a nine-center (30 tests per center) quality-control trial are < or = 0.016 to 0.032 microgram/mL for Etest, and 0.008 to 0.032 microgram/mL for broth microdilution tests from an earlier study. Because of the limited diffusion ability and bacteriostatic nature of SCH27899, MICs should be read at 80% of inhibition with agar in vitro systems (Etest, agar dilution), and the disk diffusion method is not recommended. PMID- 9990472 TI - In vitro activity of the new quinolone moxifloxacin (Bay 12-8039) against resistant gram-positive clinical isolates. AB - The novel 8-methoxyquinolone, moxifloxacin (Bay 12-8039), was compared with ciprofloxacin and eight other antimicrobials for activity against 425 strains Gram-positive clinical isolates, including 73 methicillin-resistant staphylococci, 35 vancomycin-resistant enterococci, and 80 penicillin- or eythromycin-resistant streptococci. Overall, 82% of the strains were inhibited at < or = 2 micrograms/mL. Moxifloxacin was more active than ciprofloxacin against staphylococci (8- to 32-fold), enterococci (0- to 16-fold), pneumococci (16-fold) and other streptococci (4- to 16-fold) when MIC90 results were compared. Moxifloxacin demonstrated good activity against all Gram-positive isolates tested except for ciprofloxacin-resistant enterococci (MIC90, 32 micrograms/mL) and methicillin-resistant staphylococci (MIC90, 8 micrograms/mL). Clinical trials should be initiated to define the role of this new quinolone. PMID- 9990473 TI - In vitro activity of trovafloxacin against ciprofloxacin-susceptible and resistant clinical bacterial isolates and assessment of the trovafloxacin disk test. AB - A total of 4241 consecutive clinical bacterial isolates from 10 North American medical centers were tested for susceptibility to trovafloxacin. Trovafloxacin was significantly more active than ciprofloxacin against Gram-positive bacteria, Acinetobacter spp., and Stenotrophomonas maltophilia, and resistance to trovafloxacin occurred in these groups only among isolates with high-level resistance (MIC > or = 16 micrograms/mL) to ciprofloxacin. With other species, the two drugs had comparable activity. Concerns about staphylococci and Pseudomonas aeruginosa with trovafloxacin MICs of 2.0 micrograms/mL (the upper end of the susceptible category) are discussed. Results of trovafloxacin disk diffusion test on more than 3200 nonfastidious isolates supported the FDA approved zone size interpretive criteria when the MIC breakpoint of < or = 2.0 micrograms/mL is used to define the trovafloxacin-susceptible category. PMID- 9990474 TI - Comparison of ex-vivo serum bactericidal activity of cefepime, ceftazidime and cloxacillin against Staphylococcus aureus. AB - Cefepime (1 g), ceftazidime (1 g), and cloxacillin (2 g) were administered intravenously to 10 volunteers each. After infusion of a single dose over 30 min, blood samples were obtained at 0.5, 1, 2, 3, 4, 5, 6, 8, 10, and 12 h (for ceftazidime at 0.5 and 4 h) after dosing. Drug levels were determined by the bioassay method. Serum bactericidal activity against five clinical isolates of cloxacillin-susceptible Staphylococcus aureus were determined by the microdilution method according to the National Committee for Clinical Laboratory Standards guidelines. The mean peak serum level was 76.88 +/- 24.71 mg/L for cefepime, 42.8 +/- 15.98 mL/L for ceftazidime, and 92.81 +/- 24.7 mg/L for cloxacillin. Concentrations of cefepime were detected during the whole testing period (mean trough level, 1.43 +/- 0.9 mg/L at 12 h), whereas concentrations of cloxacillin were measurable up to 5 h after administration (mean trough level, 0.90 +/- 0.97 mg/L). The mean peak reciprocal bactericidal titers were 29.41 for cefepime, 5.6 for ceftazidime, and 377 for cloxacillin. Effective bactericidal titers were detected as long as 5 h for cefepime (approximately 40% of the dosing interval) and 3 h for cloxacillin (at least 50% of the dosing interval). For ceftazidime, serum bactericidal activity was markedly lower compared with that of cefepime. Although cefepime has demonstrated an improved antistaphylococcal bactericidal activity compared with ceftazidime, it was somewhat lower than that of cloxacillin. PMID- 9990475 TI - Activity of clinafloxacin, trovafloxacin, quinupristin/dalfopristin, and other antimicrobial agents versus Staphylococcus aureus isolates with reduced susceptibility to vancomycin. AB - Isolations of Staphylococcus aureus strains with reduced susceptibility to vancomycin are now being reported worldwide. In testing here by broth microdilution according to NCCLS guidelines and applying vancomycin breakpoint criteria (susceptible at 4 micrograms/mL), two of three strains were susceptible (MICs at 4 micrograms/mL) rather than intermediate (MICs at 8 micrograms/mL) as previously reported by other laboratories. Clinafloxacin was more active (MICs/MBCs at 0.5 to 2 micrograms/mL) than ciprofloxacin, grepafloxacin, levofloxacin, ofloxacin, and sparfloxacin. Trovafloxacin, trimethoprim/sulfamethoxazole, and quinupristin/dalfopristin were the next most active agents, although quinupristin/dalfopristin was bactericidal against only two of these three strains. Amikacin, imipenem, oxacillin, and rifampin were less active. PMID- 9990476 TI - Characterization of the inoculum effect with Haemophilus influenzae and beta lactams. AB - An inoculum effect is defined as a four-fold or greater increase in MIC with an increase in bacterial inocula. Haemophilus influenzae was tested for an inoculum effect with ampicillin, cefuroxime, and amoxicillin/clavulanate using the standard initial inocula (5 x 10(5) CFU/mL) and a higher initial inocula (1 x 10(7) CFU/mL). An inoculum effect was observed with both beta-lactamase (TEM-1, ROB-1) positive and beta-lactamase negative strains of H. influenzae when MICs were determined based on turbidity. MICs based on viable cell counts however, demonstrated that only beta-lactamase positive strains of H. influenzae produced an inoculum effect. These observations suggest that MICs determined based on turbidity, using high initial inocula, are not reliable when examining the inoculum effect in H. influenzae. The magnitude of the inoculum effect with beta lactamase positive strains was beta-lactam dependent (ampicillin > amoxicillin/clavulanate > cefuroxime). beta-lactam kill-curves confirmed the aforementioned results. Addition of the beta-lactamase inhibitor clavulanate completely reversed the inoculum effect in beta-lactamase (TEM-1 and ROB-1) positive strains of H. influenzae with all beta-lactams tested. Introduction of the beta-lactamase gene TEM-1 on plasmid vector pLS88 into a beta-lactamase negative strain of H. influenzae (Rd) produced an inoculum effect based on viable cell counts. In conclusion, our results suggest that the beta-lactam inoculum effect demonstrated by H. influenzae is the result of beta-lactamase production and is poorly assessed by turbidity. PMID- 9990477 TI - In vitro activity of SCH 27899 (Ziracin) against Legionella species. AB - The activities of Sch 27899 (Ziracin), erythromycin, and ofloxacin against 102 Legionella spp. isolates were measured by a microbroth dilution method. The MICs that inhibited 90% of strains tested were 0.25, 0.5, and 0.06 microgram/mL for Sch 27899, erythromycin, and ofloxacin, respectively. The activity of Sch 27899 against intracellular Legionella pneumophila could not be determined because of complete inactivation of the drug by tissue culture medium components. PMID- 9990478 TI - Vibrio cholerae O1 serotype Ogawa in a neonate. AB - In India, cholera is endemic and affects usually the 3 to 5-year-old age group. There have been occasional reports in the neonatal period with Vibrio cholerae O139 Bengal. We report here a case of Vibrio cholerae O1 diarrhea in a 2-day-old, breastfed male, who had been delivered in the hospital and developed severe dehydration. PMID- 9990479 TI - Encapsulated Enterococcus faecalis: role of encapsulation in persistence in mouse peritoneum in absence of mouse lethality. AB - Two nonhemolytic, mucoid, encapsulated strains of Enterococcus faecalis lacked lethality for 23 white mice when inoculated (10(9) cells/mL) intraperitoneally. Bacteremia was short lived (2 to 3 days), but peritoneal cultures remained positive for 7 days postinoculation. Although encapsulation did not result in animal lethality, encapsulation may have delayed peritoneal clearance by interference with phagocytosis. PMID- 9990480 TI - Correlation of histologic morphology and tumor stage with molecular genetic analysis using microdissection in gastric carcinomas. AB - Precise correlation of histomorphology with the results of molecular genetic analysis is difficult in gastric cancer tissue composed of intestinal and diffuse types. A novel microdissection procedure was applied to correlate p53 and APC allelic loss with histologic type and tumor stage (mucosal vs. invasive cancer) in formalin-fixed, paraffin-embedded specimens of 25 gastric cancers. In addition, mucosal and invasive lesions were dissected from each of 11 invasive gastric cancers to study progression, and allelic loss of the p53 and APC genes was assessed. The p53 gene underwent loss of heterozygosity (LOH) in 4 of 4 informative cases of intestinal-type gastric cancer with mucosal lesions associated with invasion. By contrast, no p53 LOH was found among 6 informative cases with mucosal cancer. LOH of the APC gene in both intestinal and diffuse types of cancer was detected in 4 of 7 and 5 of 6 informative cases, respectively. These data suggest that allelic deletion of the p53 gene in intestinal-type gastric carcinoma predicts the invasive potential of mucosal cancer, and that inactivation of the APC gene plays a role in the genetic tumorigenesis of both intestinal and diffuse types of gastric cancer. Microdissection can correlate genetic alterations with histologic morphology in gastric cancer. PMID- 9990481 TI - Adapting in situ polymerase chain reaction for genotyping of cells in suspension. AB - An approach is described for in situ polymerase chain reaction (ISPCR) based on cycling primed in situ synthesis (PRINS) conditions defined for alpha-satellite DNA. Using blood cell preparations subjected to limited fixation with paraformaldehyde, ISPCR cycling resulted in a gradual buildup of amplicon at the site of synthesis, as judged by the characteristic presence of paired nuclear spots corresponding to specific centromeres. Using longer cycling regimens, primers for single copy genes also generated paired nuclear spots in a primer pair--specific manner. In this context, the amplification refractory mutation system (ARMS) was evaluated for in situ applications. In ARMS, allele-specific primers are used in such a manner that PCR proceeds only when an exact 3' match between annealed primer and template is recognized by DNA polymerase. Using normal and mutant primers for the delta F508 mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene as a model system, it was not possible to reliably differentiate between ARMS reactions by accumulation of direct labeled reaction product in cells, because of ARMS-independent nonspecific labeling. However, by DNA extraction and reamplification with ARMS primers, it was shown that amplicon accumulates in cells in the expected primer/template dependent manner crucial to mutation detection by ARMS. It was also shown that nonspecific signal is due to primer dimer formation, especially in the absence of true template DNA. The impact of primer dimer formation in generating a false positive signal is discussed. The method described here enables a cell population to be analyzed for a given point mutation. PMID- 9990482 TI - Amplification refractory mutation system linear extension: a novel, gel-free, enzyme-linked immunoassay method for DNA genotyping. AB - A single synthesis cycle of the amplification refractory mutation system (ARMS) was applied to the analysis of K-ras alleles amplified by polymerase chain reaction and immobilized in streptavidin-coated microtiter plates. The ARMS cycle provided the specificity and molecular switch characteristics of a conventional ARMS assay. This allowed linear extension from an allele-specific primer and the incorporation of digoxigenin-labeled deoxyuridine monophosphate from digoxigenin 11-deoxyuridine triphosphate in the presence of the appropriate K-ras allele. Any digoxigenin-labeled deoxyuridine monophosphate substitution was then demonstrated by enzyme-linked immunoassay with colorimetric endpoint. This method is capable of detecting underrepresented acquired mutations, and this has been shown by the unambiguous detection of specific K-ras mutations in cell line DNA/normal human genomic DNA admixtures. The characterization of K-ras mutations in frozen colorectal tumor samples and histologic material is also described. PMID- 9990483 TI - Cyclin D1 gene amplification and p16 gene deletion in patients with esophageal carcinosarcoma. AB - Cyclin D1 (CD1) gene amplification is frequently observed in esophageal carcinosarcoma by differential polymerase chain reaction (DPCR). In this study, fluorescence in situ hybridization (FISH) was performed to show more direct evidence of CD1 gene amplification in patients with esophageal carcinosarcoma. FISH results were also compared with DPCR results studied previously. FISH analysis revealed CD1 gene amplification in all four patients with esophageal carcinosarcoma. CD1 gene amplification occurred with a high incidence in both components of esophageal carcinosarcoma, suggesting that CD1 gene amplification could have an important role in malignant transformation processes of esophageal carcinosarcoma. The results of the current study also suggest that FISH is a more sensitive method than DPCR. Because inactivation of p16 gene (which is a putative tumor suppressor gene) is thought to have similar oncogenic effects with CD1 gene amplification, DPCR was used to examine whether p16 homozygous deletion occurs in esophageal carcinosarcoma. These results suggest that homozygous deletion of the p16 gene occurs less frequently than CD1 gene amplification in esophageal carcinosarcoma. It does not seem to be an alternative event to CD1 gene amplification, though the number of studied cases was small. PMID- 9990484 TI - Establishing germ cell origin of undifferentiated tumors by identifying gain of 12p material using comparative genomic hybridization analysis of paraffin embedded samples. AB - An estimated 10% of adult cancer patients present with undifferentiated carcinoma. The diagnosis of germ cell tumor (GCT) in such patients can be difficult but has important implications for patient management. Male testicular GCT is characterized by an isochromosome 12p, i(12p), or additional 12p material, in some cases restricted to the 12p11.2-p12.1 region. A gain of 12p material can indicate that a tumor, which may not be present in the testis, is of germ cell origin. Formalin-fixed, paraffin-embedded samples are the most widely available material for diagnostic analysis and retrospective studies. We have compared the identification of 12p gain in snap-frozen samples with corresponding paraffin embedded material from three clearly defined testicular GCTs using comparative genomic hybridization analysis. In this preliminary study, paraffin-embedded tumor samples of uncertain histogenesis from seven patients were then analyzed. Tumor samples from three of these patients showed a gain of 12p material, and in one patient, gain was restricted to the 12p11.2-p12 region. The clinical picture and response to therapy were generally consistent with the 12p status, though lack of 12p gain may not exclude a diagnosis of GCT. PMID- 9990485 TI - Histologic distribution of hepatitis A, B, C, D, E, and G with concomitant cytokine response in liver tissue. AB - The purpose of this study was to determine the frequency of infection by hepatitis A, B, C, D, E, and G in liver biopsy specimens from symptomatic patients and to correlate viral localization with the expression of interferon tau, interleukin 4, and tumor necrosis factor messenger RNA. Tissue biopsy specimens were taken from 78 patients as follows: 14 patients with transplants, 23 patients with cirrhotic livers, and 41 patients with chronic hepatitis. At least one of the hepatitis viruses was detected in 60 of 78 (77%) specimens; multiple infection was evident in 18 of 78 (23%) specimens. The overall incidence of the different viruses was as follows: 8% hepatitis A, 3% hepatitis B, 52% hepatitis C, 1% hepatitis D, 24% hepatitis E, 18% hepatitis G. Throughout each category, hepatitis C was the most common virus detected. No histologic variable correlated with either the percentage of infected hepatocytes per lobule or nodule or with the specific viral type. The cytokines localized to monocytes or lymphocytes adjacent to infected hepatocytes. These results demonstrate that viral infection is present in most biopsy specimens of patients with chronic hepatitis and liver transplants and that hepatitis C, E, and G account for most of the infections. The results also suggest that direct viral infection in conjunction with expression of different cytokines is important in the pathophysiology of viral-induced liver disease. PMID- 9990486 TI - Low incidence of microsatellite instability in patients with cervical carcinomas. AB - Alterations in microsatellite sequences have been reported in a variety of human cancers. Microsatellite instability is thought to reflect the inactivation of genes involved in DNA mismatch repair (MMR), which could predispose to the accumulation of further genetic errors in affected cells. Genomic instability in human cancers might also result from the inactivation of cell cycle controls such as the p53-dependent G1 checkpoint that prevents cell replication in response to DNA damage. High-risk human papillomavirus (HPV) is thought to contribute to the development of HPV-associated cancers, including cervical carcinoma, through the interaction of the E6 and E7 viral oncoproteins with two major cell cycle regulatory proteins, namely p53 and the retinoblastoma gene product (pRb). Although the high-risk HPV is prevalent in cervical carcinomas, viral DNA is not detected in a minor proportion of the cases. The HPV infection is insufficient for the development of cervical cancer, which indicates that additional genetic events are involved in the process. This study reports the potential role of MMR gene defects (in addition to or independent of HPV infection) in patients with cervical carcinogenesis. Microsatellite instability and HPV status were analyzed in a series of 54 patients with cervical carcinomas and in two associated cell lines. Microsatellite alterations were examined at 10 loci located in different chromosomes by using semiautomated fluorescent DNA technology and polymerase chain reaction. The HPV types were detected by a general primer polymerase chain reaction method. The results indicate that microsatellite instability is very infrequent in cervical carcinoma and occurs independently of HPV status. PMID- 9990487 TI - Characterization of a variant SYT-SSX1 synovial sarcoma fusion transcript. AB - Synovial sarcoma is characterized cytogenetically by an X;18 translocation [t (X;18) (p11;q11)] that results in the fusion of the SYT gene from chromosome 18 to either of two highly homologous genes at Xp11, SSX1 or SSX2. Heterogeneity within the synovial sarcoma fusion junctions is rare. Examination of a primary monophasic synovial sarcoma for an SYT-SSX fusion transcript by reverse transcription polymerase chain reaction revealed a smaller-than-expected product. Direct sequencing of the product disclosed a novel SYT-SSX1 fusion transcript that contained an additional 51 bp of normal SSX1 sequence but lost 135 bp of the SYT sequence. Detection of synovial sarcoma hybrid transcripts is useful for diagnosis and should include the recognition of distinct variants. PMID- 9990488 TI - What does a home mean and when does it cease to be a home? Home as a setting for rehabilitation and care. AB - PURPOSE: This article addresses three issues: (1) what does a home mean to a person? (2) what happens when the patients are rehabilitated in the home? and (3) can the home become a workplace for a professional? METHOD: A literature review based on research literature and on the author's research project in the north of Sweden 'Rehabilitation in a home setting--ethical, psychological and occupational therapeutic aspects,. RESULTS: For most people, the home is an important and meaningful place, where ultimate goals can be cultivated, sheltered from the intrusions of public life. In connection with chronic illness, functional impairment and rehabilitation in the home, the individual will often lose the home as a private territory and much of his/her own autonomy. No longer is the home an existential centre for the family, but a place where many unfamiliar people come and go. Rehabilitation in a home setting means, furthermore, that the public sector is moved into the home, and the home has to function as a public workplace, ensuring a good working environment. CONCLUSIONS: The question for the future is: can the combination of home and public workplace work at all? More research is needed to answer this question. Prior documented experiences show that it is difficult. PMID- 9990489 TI - Use of technology by people with physical disabilities in Australia. AB - PURPOSE: This study aimed to quantify the extent to which computers and assistive devices were being used by people with physical disabilities and the levels of computer training being undertaken by this group. METHOD: With the help of Queensland disability associations a written survey was distributed to people over 15 years in age with physical disabilities living in the greater Brisbane metropolitan area. Responses were received from 82 people (comprising spinal cord injuries (n = 71), cerebral palsy (n = 8), muscular dystrophy (n = 3)). RESULTS: Indicate that 60% of respondents were computer users, while only 15 respondents used assistive devices. Computer ability was correlated to age and time of disability onset. Respondents with quadriplegia had higher levels of computer ability than those with paraplegia. The study indicates that while many people with disabilities have used computers and assistive devices, many have not. CONCLUSIONS: The low rate of assistive device use by people with high-level quadriplegia is of concern. This study suggests that increased levels of training in the use of computers and assistive devices needs to be provided to people with physical disabilities. PMID- 9990490 TI - Measuring disability, the agreement between self evaluation and observation of performance. AB - PURPOSE: In 1981, eight countries and the World Health Organization (WHO) reached consensus about applying a similar disability questionnaire in their health surveys that was related to the ICIDH. In 1992 a revised version, the WHO disability questionnaire, was recommended. In this paper the concurrent validity of 10 items of the questionnaire is evaluated by measuring the agreement with observed performance of corresponding tasks. METHOD: The disability questionnaire was sent to 750 subjects. From the respondents (468) 93 were selected, based on their reported disability, and 10 performance tasks were observed. The agreement was measured for individual items and for all items together in distinguishing between persons with no, or at least one disability. RESULTS: A low to moderate agreement was found between self reported and observed disability. In general, observation resulted in lower disability ratings. Among 24% of those who reported at least one disability, no disability was observed. Persons among whom at least one disability was observed, only 2% (n = 1) reported no disability in the questionnaire. CONCLUSIONS: Although the concurrent validity is low to moderate between the results of the WHO-disability questionnaire and observation, the questionnaire is highly sensitive for detecting persons with at least one disability. The specificity of the questionnaire must be increased by additional questions. PMID- 9990491 TI - Effects of physical training on straightening-up processes in patients with Parkinson's disease. AB - PURPOSE: The aim of this study was to evaluate whether motor training could improve the straightening-up sequences in patients with Parkinson's disease and, consequently, could ease the capacity of the patients to change body's position. METHODS: Twenty out-patients with idiopathic Parkinson's disease (12 males, 8 females; mean age 72.9; H-Y, 1. 5-3) were enrolled in a rehabilitation programme which included exercises for the mobility of the trunk, of upper and lower limbs and of each segment of the spine, in order to improve the coordination of movement and to avoid postural disturbances. They received 1 hour of group treatment twice a week for a 5 week consecutive period. No changes were made in the pharmacological treatment received by each patient. The patients were evaluated at the beginning and at the end of the rehabilitation training. The statistical evaluation was made using the Wilcoxon test. RESULTS: Statistically significant differences were observed in all the motor parameters that were evaluated (supine to sitting and sitting to supine, supine rolling, standing from a chair). CONCLUSIONS: The observations demonstrate that physical training can be effective in improving motor performance related to changes in position which affects the simple daily activities of the patients. PMID- 9990492 TI - Disability in ankylosing spondylitis. AB - PURPOSE: This study was designed to examine the functional loss in ankylosing spondylitis and explore the relationship between disability and various factors such as age, disease duration, disease activity, spinal mobility, chest expansion, peripheral joint involvement, radiological changes, and psychosocial well-being. METHOD: Forty-two patients were included in this cross-sectional study. RESULTS: The results showed that 37 patients had mild to moderate disability, two patients had severe disability, and three patients did not report any functional loss. Spearman correlation analyses showed that disability was strongly correlated with spinal mobility measures, disease activity measures, and disease duration. Also, patients with peripheral joint involvement had greater disability. When the predictive effect of five independent variables was studied by multiple regression analysis, it was found that the most powerful predictors of functional loss in AS patients were cervical rotation, modified Schober's test, and pain. CONCLUSIONS: These data suggest that functional consequences of AS are constituted by multiple impairments and each needs to be managed by an integrated physiatric approach. PMID- 9990493 TI - The rehabilitation process for the geriatric stroke patient--an exploratory study of goal setting and interventions. AB - PURPOSE: The aim was to describe and analyse the rehabilitation process of the geriatric stroke patient from two perspectives; the treatment goals expressed by the staff and the patient and the treatment interventions chosen by the physiotherapist and occupational therapist. A secondary aim was to test whether the process, treatment goals and interventions could be classified according to the International Classification of Impairments, Disabilities and Handicaps (ICIDH). METHOD: Qualitative interviews were performed with patients and personnel; diaries were used to register treatment interventions. The 30 interviews were categorized according to the goals expressed by physiotherapists, occupational therapists, physicians and patients. The diaries (n = 22) were analysed to describe how treatment interventions were connected in time, at what levels (impairment, disability and handicap) the interventions were directed, and finally, whether certain decisions were made in order to change the rehabilitation process. RESULTS: The patients talked more about attaining their pre-stroke status than about their goals. The therapists set goals according to functional level, whereas the doctors expressed themselves in general terms. Three patterns of rehabilitation processes were found: one with clearly identified decision points, one with a set programme which was not changed through the process, and one where the goal was changed according to changes in medical status. CONCLUSIONS: The patient does not participate in the goal-setting process, and the vaguely expressed goals are not measurable. The rehabilitation process and reason for discharge demonstrate different patterns. Treatment interventions, if related to the ICIDH, give a clear picture of the process, though certain interventions do not fit in the classification. PMID- 9990494 TI - Determinants of medico-social functioning after total gastrectomy. AB - AIM: To describe medico-social functioning after total gastrectomy and the factors determining it. PATIENTS AND METHODS: In three medical rehabilitation centres, 173 consecutive patients (female/male = 62/111) after potentially curative total gastrectomy for gastric malignancy 206 days earlier (median, interquartile range = IQR 56-644) were evaluated for different pre- and post operative parameters with potential influence on post-operative medico-social functioning as measured with the Edinburgh Rehabilitation Status Scale (ERSS). Parameters evaluated were: gender, age, time since operation, tumour stage, type of operation, clinical centre of admittance, haemoglobin, ferritin, albumin, presence of small bowel bacterial overgrowth, rapid oro-coecal transit, dyspepsia, early satiety, reflux, dysphagia, vomiting, a symptom based score, body mass index in health, at operation and on admission, weight loss since operation, calorie intake, bowel habits, and fat malassimilation. Independent influential factors for the ERSS were identified in a linear regression analysis. RESULTS: The median ERSS-score was 4 (IQR 2-6) on a scale from 0 (best) to 28 (worst). There was a significant difference in the ERSS-scores between the three different clinics. The ERSS-scores improved significantly with time since operation (ca. 22% per year). ERSS-scores were higher in patients with intestino oesophageal reflux (+71%), with dyspepsia (+65%), or with dysphagia (+62%). CONCLUSION: Medico-social functioning was acceptable in this patient population. After total gastrectomy, dyspepsia, dysphagia, and intestinal reflux into the oesophagus need special attention. PMID- 9990495 TI - An understanding with people. PMID- 9990496 TI - Teaching about family violence when the trainee is also a survivor. PMID- 9990497 TI - Correlations of family medicine clerkship evaluations and Objective Structured Clinical Examination scores and residency directors' ratings. AB - BACKGROUND AND OBJECTIVES: This study validated the evaluation methods used in a family medicine clerkship by comparing students' scores to how students are rated in their first year of residency by residency directors. The clerkship evaluations consisted of three components: problem solving in small groups, clinical evaluations, and a final examination. These components were combined to form a composite clerkship score. Residency director ratings consisted of 20 individual scores and an overall average. METHODS: Scores received by students in the clerkship were correlated with ratings by residency directors given toward the end of the first year of residency. The correlations between Objective Structured Clinical Examination (OSCE) scores and residency directors' ratings were used as comparison. RESULTS: The composite clerkship score correlated with the director's rating, overall average, at r = .278. The highest individual component correlation was achieved by the clerkship final exam (r = .269). The total OSCE score correlated with the director's rating overall average at r = .304. CONCLUSIONS: This study provides evidence that, while not perfect, the family medicine clerkship evaluations perform nearly as well as the OSCE as a predictor of how students will be rated by their residency directors in their first year of residency. PMID- 9990498 TI - Didactic content and teaching methodologies on required allopathic US family medicine clerkships. AB - BACKGROUND AND OBJECTIVES: Despite the increased prominence of family medicine clerkships in required third- and fourth-year clinical rotations in US allopathic medical schools, the content of these clerkships varies markedly among institutions, and there is little in the literature concerning the current or desired content of family medicine clerkships. This study explores the didactic content of a national sample of required family medicine clerkships to assess what and how this important aspect of clerkship curriculum is taught. METHODS: Using an original survey instrument, we surveyed US medical schools through mailings and follow-up phone contacts. We categorized free-form responses using a coding dictionary specific to this study and computed descriptive statistics. RESULTS: Of 127 medical schools contacted, 105 (83%) responded. Among respondents, 86 (82%) had a required family medicine clerkship, 80% of them in the third year. Mean clerkship length was 5.3 weeks (median = 4 weeks), and the mean number of didactic sessions was about 2 per week. Almost 80% of clerkships had sessions in the broad area of family medicine, and prevention was the most frequent individual topic, taught in 32 (37%) of clerkships. Seventy-one percent of sessions used methodologies other than lectures. The mean time devoted to teaching 24 of the top 26 topics identified in the survey was between 1.2 and 3.1 hours/rotation, although case presentations and common problems each averaged more than 7 hours on clerkships teaching these topics. CONCLUSIONS: This survey provided more detailed information than previously available about the didactic content of required US allopathic family medicine clerkships. The survey also documented the lack of agreement among these clerkships on didactic content. Most didactic sessions used interactive rather than lecture format. The information from this first detailed survey provides family medicine clerkship directors with national comparisons of didactic content and methodology as a foundation for further discussion. PMID- 9990499 TI - Effects of viral respiratory disease education and surveillance on antibiotic prescribing. AB - BACKGROUND AND OBJECTIVES: We describe a partnership between family practice residency clinics and a state public health virology laboratory that has produced comprehensive viral respiratory disease education and surveillance. Family practice residents have been provided with education on respiratory viruses and the results of ongoing viral surveillance. The preliminary effects of this program on antibiotic prescribing by senior residents are evaluated in this paper. METHODS: We used a questionnaire to assess the acceptance by family practice residents of the educational component and the utility of ongoing viral surveillance. We used chart review to evaluate rates of antibiotic prescribing and the number of patients diagnosed per year with acute upper respiratory infection and acute bronchitis by senior residents in 1992 (preexposure) and 1996 (postexposure). RESULTS: By the third year of training, most residents (79%) reported receiving adequate training regarding common viral respiratory diseases. Moreover, residents reported that they were less likely to prescribe antibiotics to patients presenting with respiratory infections when provided with specific information on circulating viral pathogens. Antibiotic prescribing in the postexposure group was 68% lower for upper respiratory infection (URI) and 45% lower for a composite of URI and bronchitis. CONCLUSIONS: Education and monitoring of circulating respiratory viruses can result in familiarity with common disorders in primary care and reduce unnecessary antibiotic use. PMID- 9990500 TI - Teaching practice management during residency. AB - BACKGROUND AND OBJECTIVES: Practice management is a required component in family practice residency education. A few studies have reported that recently graduated primary care physicians indicated that their practice management training was inadequate. Our study describes the current nature of practice management education in family practice residencies and the perceptions of residency directors about the effectiveness of their program's practice management curriculum. METHODS: Surveys were mailed to 421 family practice residency directors, who were asked about their program's curriculum approach to teaching practice management, as well as their evaluation of the effectiveness of the curriculum. After two mailings, 213 surveys (51%) were returned. RESULTS: Eighteen percent of the respondents provided less than the required 60 hours of practice management curricular time. Residency directors indicated that managed care has had a significant effect on their curriculum. Directors' ratings of the effectiveness of their curriculum were associated with more curricular time and specifically with active learning activities. Although directors reported that managed care had affected how they teach practice management, managed care penetration was not associated with perceived curriculum effectiveness. CONCLUSIONS: Family practice residency program directors described a variety of approaches to teaching practice management. Active learning strategies seem to be important curricular components, although further study is needed about the most effective methods to prepare physicians for post-residency practice. PMID- 9990501 TI - Evaluating programs for recruiting and retaining community faculty. AB - BACKGROUND AND OBJECTIVES: There is a need to develop ambulatory care components within medical schools and, accordingly, a need to recruit community faculty. To assist in recruiting and retaining community faculty, this study addresses factors influencing physicians' decisions to serve as preceptors. The study also examines the relative value of incentives as rated by physicians in different primary care specialties. METHODS: We surveyed community physicians affiliated with a large, public teaching hospital. Physicians rated prior experiences training students in ambulatory settings, plans for serving as preceptors within the next year, and 7 incentives for serving as preceptors. RESULTS: A path analysis indicated that prior experiences and student influence on patient care affected future decisions to serve as preceptors. Analysis of the incentives for serving as preceptors indicated that physicians rated receiving continuing medical education (CME) credit the most favorably and financial compensation the least favorably. Overall, family physicians assigned the highest ratings to the incentives, and gynecologists gave the lowest ratings. CONCLUSIONS: This study produced a better understanding of the factors influencing physicians' decisions to serve as preceptors. Physicians are more concerned about students' influence on patient care than they are about students' influence on patient billings. In addition, preceptors preferred receiving nonmonetary compensation, such as CME credit, rather than receiving financial compensation. In addition, this study suggests better ways to reward community physicians for their service as preceptors. Community faculty should not be viewed as a homogenous group. The results of this study suggest that community physicians be provided with choices regarding the incentives for and rewards associated with serving as preceptors. PMID- 9990502 TI - Relationship of nutrition knowledge and obesity in adolescence. AB - BACKGROUND: The prevalence of obesity in adolescence is increasing. This study determined whether a lack of nutrition knowledge is correlated with obesity in adolescents. METHODS: We distributed a survey at three high schools to 292 9th through 12th-grade students. The questionnaire examined the students' nutrition knowledge, food-related behaviors, and food preferences. The students' body mass indices (BMI) were calculated from self-reported weights and heights. Obesity was defined as a BMI greater than the 85th percentile, using criteria from the National Health and Nutrition Examination Survey II. RESULTS: Of 292 students contacted, 289 returned the survey. The population had a prevalence of obesity of 26%. There were no significant differences in nutrition knowledge between the obese and non-obese students with the exception that obese students were better able to identify high-fiber foods. In addition, obese students were more likely to report infrequent meals with their family. Otherwise, there were no significant differences in nutrition behaviors or food preferences. CONCLUSIONS: Overall nutrition knowledge did not differ between obese and non-obese adolescents. PMID- 9990503 TI - Patterns and correlates of tobacco use among suburban Philadelphia 6th- through 12th-grade students. AB - BACKGROUND AND OBJECTIVES: Tobacco use among teenagers is increasing, even in the face of an understanding of its harmful effects. Data suggest that tobacco use often begins before entrance to eighth grade. This study examined the prevalence of tobacco use among students in 6th grade and compared it to the prevalence of tobacco use among 8th, 10th, and 12th graders in a northeastern suburban community and to national data. METHODS: We used a survey that measured selected tobacco and smokeless tobacco use, demographic variables, school-related factors, and social influences on the use of tobacco products. RESULTS: Sixth-grade tobacco use existed but was minimal compared to the rates seen in 8th, 10th, and 12th graders. Only 1% of 6th graders reported they were current smokers, compared with 41% of 12th graders. Risk factors for becoming a smoker were smoking habits of parents, siblings, and friends. CONCLUSIONS: Cigarette experimentation and use begins as early as sixth grade and increases substantially by eighth grade. Our data suggest that efforts toward primary prevention of smoking should be pursued between sixth and eighth grade. PMID- 9990504 TI - The patient, the teacher. PMID- 9990505 TI - Role of Bcl-2 family proteins in apoptosis: apoptosomes or mitochondria? AB - Apoptosis is an essential physiological process for the selective elimination of cells, which is involved in a variety of biological events. The Bcl-2 family is the best characterized protein family involved in the regulation of apoptotic cell death, consisting of anti-apoptotic and pro-apoptotic members. The anti apoptotic members of this family, such as Bcl-2 and Bcl-XL, prevent apoptosis either by sequestering proforms of death-driving cysteine proteases called caspases (a complex called the apoptosome) or by preventing the release of mitochondrial apoptogenic factors such as cytochrome c and AIF (apoptosis inducing factor) into the cytoplasm. After entering the cytoplasm, cytochrome c and AIF directly activate caspases that cleave a set of cellular proteins to cause apoptotic changes. In contrast, pro-apoptotic members of this family, such as Bax and Bak, trigger the release of caspases from death antagonists via heterodimerization and also by inducing the release of mitochondrial apoptogenic factors into the cytoplasm via acting on mitochondrial permeability transition pore, thereby leading to caspase activation. Thus, the Bcl-2 family of proteins acts as a critical life-death decision point within the common pathway of apoptosis. PMID- 9990506 TI - Analysis of mammalian origin specification in ORC-depleted Xenopus egg extracts. AB - BACKGROUND: Xenopus egg extracts initiate replication specifically at the Chinese Hamster Ovary (CHO) cell dihydrofolate reductase (DHFR) origin with CHO G1-phase nuclei as a substrate, providing that these nuclei have intact nuclear envelopes and are isolated from cells that have passed through a distinct transition (origin decision point; ODP) early in G1-phase. With intact pre-ODP nuclei, or with post-ODP nuclei that have permeabilized nuclear envelopes, replication initiates efficiently but, at apparently random sites. We have investigated whether the Xenopus embryonic origin recognition complex (XORC) influences origin specification in this system. RESULTS: Xenopus egg extracts were immunodepleted of XORC, eliminating their ability to assemble pre-initiation complexes. These extracts were deficient in the replication of CHO metaphase chromosomes but supported efficient DNA replication within both pre- and post-ODP hamster G1 phase nuclei, even after permeabilization and extraction of soluble nuclear proteins. XORC-depleted extracts initiated replication specifically at the DHFR origin with intact post-ODP nuclei but still initiated at apparently random sites with intact pre-ODP nuclei or permeabilized post-ODP nuclei. CONCLUSIONS: Xenopus embryonic ORC is clearly not required for random origin site selection in Xenopus egg extracts. We conclude that a modification of Chinese Hamster chromatin takes place shortly after metaphase that complements a lack of XORC activity. This modification most likely represents an interaction of mammalian ORC with chromatin that is required for replication but, that is not sufficient for origin specification. PMID- 9990507 TI - Two F-box/WD-repeat proteins Pop1 and Pop2 form hetero- and homo-complexes together with cullin-1 in the fission yeast SCF (Skp1-Cullin-1-F-box) ubiquitin ligase. AB - BACKGROUND: In the ubiquitin-dependent proteolysis pathway, a ubiquitin ligase (E3) is responsible for substrate selectivity and timing of degradation. A novel E3, SCF (Skp1-Cullin-1/Cdc53-F-box) plays a pivotal role in cell cycle progression. In fission yeast, F-box/WD-repeat protein Pop1 regulates the level of the CDK (cyclin-dependent kinase) inhibitor Rum1 and the S phase regulator Cdc18. RESULTS: We have cloned and characterized the pop2+ gene which encodes the Pop1-related F-box/WD-repeat protein. Pop2 plays a role which overlaps with Pop1 in the degradation of Rum1 and Cdc18. However, these two proteins are not functional homologues. Pop1 and Pop2 form hetero-as well as homo-dimers in the cell. We have analysed two fission yeast cullin members and found that cullin-1 functions as a component of SCFPop1,2, whilst cullin-3 is involved in the distinct stress-response pathway. CONCLUSIONS: Fission yeast SCF is composed of Pop1 and Pop2, two structurally related but functionally independent F-box/WD repeat proteins. By forming three distinct complexes, SCFPop1/Pop1, SCFPop1/Pop2 and SCFPop2/Pop2, SCF has evolved a sophisticated mechanism to control the level of Rum1 and Cdc18. Fission yeast SCF also contains cullin-1 as a universal scaffold and each cullin member plays a distinct biological role. PMID- 9990508 TI - Cell cycle dependent topological changes of chromosomal replication origins in Saccharomyces cerevisiae. AB - BACKGROUND: The ORC (Origin Recognition Complex) of Saccharomyces cerevisiae is a protein complex for the initiation of replication which interacts with a cis element, ACS (ARS Consensus Sequence), essential for DNA replication. The protein DNA complex detected by the DNase I genomic footprinting method has been shown to vary depending on cell cycle progression. Further studies on topological changes of replication origin in vivo caused by ORC association are crucial for an understanding of chromosomal DNA replication in S. cerevisiae. RESULTS: Topological changes in the replication origins of the S. cerevisiae chromosome were studied by an in vivo UV photofootprinting method which is capable of detecting the change in the flexibility of DNA caused by protein binding. The footprinting method detected the inhibition and enhancement of UV-induced pyrimidine dimer formation in A and B1 elements of a chromosomal origin, ARS1, depending on the activity of native ORC subunits. Furthermore, footprint patterns were reproduced in vitro with purified ORC. The inhibition regarding the A element was stronger during the S to late M phase than that during the progression through the G1 phase. Functional CDC6 and MCM5 were required for maintaining the weaker inhibition state in G1-arrested cells. CONCLUSION: The application of in vivo UV photofootprinting in studies of topological changes of S. cerevisiae replication origins revealed the presence of two modes of topological ORC-ACS interaction. The weaker footprint in the G1 phase represents a specific topology of ACS, resulting from an alteration of the ORC-ACS interaction aided by CDC6 and MCM5, and this topological change may make the replication origin competent for initiating DNA replication. PMID- 9990509 TI - Human ubiquitin-protein ligase Nedd4: expression, subcellular localization and selective interaction with ubiquitin-conjugating enzymes. AB - BACKGROUND: Nedd4 is a ubiquitin-protein ligase containing a calcium/lipid binding domain, multiple WW domains and a C-terminal Hect domain, which is required for both the ubiquitin transfer and the association with E2 ubiquitin conjugating enzymes. Nedd4 has been reported to be involved in the selective ubiquitination of some regulatory proteins in transcription and membrane transport. RESULTS: Three mRNA species for human Nedd4 were found to be 6.4-, 7.8 and 9.5-kb in size, and their expression patterns varied among normal tissues and cancer cell lines, indicating the tissue- and cell-specificities of Nedd4 expression. The Nedd4 protein, approximately 120 kDa in weight, was found in the cytoplasm, mainly in the perinuclear region and cytoplasmic periphery, of human cultured cells. Neural differentiation induced not only the down-regulation of Nedd4 but also the localization of the protein to both the cytoplasm and neurites. To identify the ubiquitination pathway that is linked to Nedd4, we demonstrated that specific E2 enzymes, including human Ubc4, UbcH5B, UbcH5C, UbcH6 and UbcH7, could transfer ubiquitin molecules to Nedd4 at the active cysteine residue, whereas E6AP accepted ubiquitins from Ubc4, UbcH5B, UbcH5C and UbcH7. Furthermore, nuclear localization of N-terminal deletion mutant Nedd4 enabled us to investigate the interaction between Nedd4 and E2 enzyme (Ubc4 or UbcH7) in the cell. The simultaneous expression of the full-length Nedd4 and E2 enzyme revealed the both proteins mostly colocalized in the cytoplasmic periphery, while the N-terminal deleted Nedd4 induced the nuclear and perinuclear colocalization with E2 enzyme. CONCLUSION: Our findings suggested that Nedd4 plays an important role in the cell regulation, including neural differentiation through cooperation with specific E2 ubiquitination pathways. PMID- 9990510 TI - ECRI position statement on the testing of medical devices for year 2000 compliance. PMID- 9990511 TI - Year 2000 testing of interfaced medical devices. PMID- 9990512 TI - Thoracic aspirators. PMID- 9990513 TI - Release of Ethicon Endopath Tri-Star trocar/cannula gaskets into pneumoperitoneum leads to design change. PMID- 9990514 TI - Image can be reversed between scout and axial views on Elscint CT Twin and Helicat computed tomography scanners. PMID- 9990515 TI - Reimagining family therapy: reflections on Minuchin's invisible family. PMID- 9990516 TI - Retelling, reimagining, and re-searching: a continuing conversation. PMID- 9990517 TI - The basic skills evaluation device. AB - The Commission on Accreditation for Marriage and Family Therapy Education (COAMFTE) requires that accredited programs evaluate trainees' clinical skills at various times during trainees' programs. The Commission does not attempt, however, to describe for programs either the nature of the skills nor how they are to be evaluated, leaving this to the programs to create. This paper describes the development and uses of the Basic Skills Evaluation Device (BSED). Using a published list of skills (Figley & Nelson, 1989), data from the literature, and data collected from COAMFTE accredited and candidacy programs, the authors and their colleagues developed a device for supervisors to use in evaluating beginning family therapists. Data regarding the reliability of the device are presented, along with limitations and suggestions for various ways of using the device. PMID- 9990519 TI - Ethnic identity development of internationally adopted children and adolescents: implications for family therapists. AB - The life story of the internationally adopted child tends to be an emotional one. How the story is told and retold in the family can have lasting consequences for the child's adjustment and well-being. In telling the story, parents are faced with a unique challenge: To what extent is it desirable to encourage their children, who already struggle with identity issues related to adoption, to identify with their cultures of origin? Therapists working on these issues with multiethnic adoptive families can find little guidance in the family systems literature. To fill this gap, the present article reviews the literature on racial/ethnic identity development and the available research on ethnic identification, self-esteem, and the psychological adjustment of cross-ethnically adopted children and adolescents. Implications for practice include developmental considerations, identifying children and families at risk, and recommendations for those in need of intervention. PMID- 9990518 TI - The relationship between psychiatrists' couple and family therapy training experience and their subsequent practice profile. AB - A 28-item questionnaire was returned by 291 psychiatrists who had completed training between 1962 and 1992. There were positive correlations between the amount of couple and family therapy training (CFTT) they received and the following: the extent to which graduate psychiatrists practice CFT; their involvement as supervisors, teachers, teaching program directors, or researchers; the extent to which they seek continuing education in CFT; their positive attitude toward CFT; and the extent to which they feel that their attitude to and interest in CFT has had a positive effect on the milieu in which they practice and on their personal lives. PMID- 9990520 TI - Change, disengagement, and renewal: relationship dynamics between young adults and their fathers after divorce. AB - Little is known about children's perceptions of their parents' divorce or how children construct meaning around the divorce and their subsequent relationships with their parents. The focus of this study was to learn about the experiences and the meanings young adults had constructed about the divorce process and their relationships with their fathers in the years after the divorce. The findings revealed a broad spectrum of experiences and several key issues that gave meaning to both the disengagement and the reengagement with their fathers. Loss, trust, acceptance, availability, and support are a few of the vital issues addressed. Implications for family therapists are discussed. PMID- 9990521 TI - Designing constructive therapies in community mental health: poetics and micropolitics in and beyond the consulting room. PMID- 9990522 TI - An alternative to managed care: a "guild" model for the independent practice of psychotherapy. AB - As health care is reconfigured by HMOs and managed care organizations, family therapists often have to decide whether or not to cooperate with the new power structures and their ways of doing things. The chief concern of many therapists is the ethical bind created when the managed care organization demands breaches of confidentiality or makes decisions about the course of treatment that may not, in the therapist's opinion, be in the best interest of the family. Associations of independent, nonmanaged care psychotherapists are springing up in response to these dilemmas. This paper describes the philosophical evolution and organizational development of one such association. PMID- 9990523 TI - Influences on the inclusion of children in family therapy. AB - This study examined factors that influence family therapists to include children in or exclude them from therapy sessions. We hypothesized that therapist comfort, child problem type (internalizing vs. externalizing), family composition (one- vs. two-parent families), and presenting problem (child-oriented problem vs. adult-oriented problem) affect therapists' inclusion of children. A survey of clinical members of AAMFT found that half of the therapists excluded children on the basis of their comfort and that those who felt more comfortable were more likely to include children in sessions. Therapists included children more frequently in cases of an internalizing vs. an externalizing child, more with single-parent than two-parent families, and more often when the presenting problem focused on a child than on an adult. Implications of the findings are discussed. PMID- 9990524 TI - Microvascular involvement in cardiac pathology. AB - Abnormalities of the microvasculature are centrally involved in the pathogenesis of some forms of heart disease, but in others are consequences of it. Microvascular abnormalities may contribute to the progression of viral myocarditis and Chagas' disease. Focal abnormalities may occur early in some cardiomyopathies and do occur later in most types of myocarditis. The thickening of arteriolar walls in chronic hypertension is likely to contribute significantly to the impairment of coronary haemodynamics associated with adaptive ventricular hypertrophy and the consequent diminution of coronary reserve, increasing diffusion distances and failure of angiogenesis to compensate. However, the resulting myocyte necrosis stimulates inflammatory angiogenesis. When ischemic myocyte injury becomes irreversible there is a concomitant loss of capacity for reperfusion, the no-reflow phenomenon. Less severe temporary ischemia reduces the proportion of functional capillaries. Multiple mechanisms are involved in this microvascular stunning, including: reperfusion injury; leukocyte activation; adhesion and accumulation; and impaired endothelium-dependent vasodilation. Many of the microvascular changes are those of the inflammatory response to cell death and form part of a final common pathway in myocarditis, cardiomyopathy, cardiac hypertrophy and failure, and ischemic heart disease. Stimulation of angiogenesis prior to myocyte necrosis in hypertrophy and control of leukocyte activity in ischemic heart disease could minimize myocyte loss. PMID- 9990525 TI - Capillaries, caveolae, calcium and cyclic nucleotides: a new look at microvascular permeability. AB - Over the past 35 years much effort has been directed at identifying the pathways through microvascular endothelium and unravelling the interactions between the convective and diffusive forces which drive fluid and solutes through them. While increases in permeability induced by inflammatory mediators are known to result from the formation of gaps in venular endothelium, it is only recent advances in cell biology that have allowed the mechanisms regulating permeability to be investigated from a sound base. Results from the general biology of vesicular transport have been applied in studies on the caveolae of microvascular endothelium. Work on single perfused microvessels and on endothelial cell cultures have revealed the importance of intracellular Ca2+ and both cAMP and cGMP in regulating permeability. Even the belief that permeability is increased by gaps developing between the cells has been challenged. Although the mechanisms regulating permeability remain far from clear, sensible hypotheses can now be proposed and tested. PMID- 9990527 TI - Inflammatory alterations in the myocardial microcirculation. AB - Inflammatory mechanisms are involved in the pathophysiology of cardiovascular disease and the present review focus us on the association between inflammation and microvascular endothelial dysfunction in the heart, i.e. reduced endothelium dependent vasodilation of coronary resistance vessels. This abnormality is caused by reduced bioactivity of nitric oxide (NO), and it is found in a variety of conditions, including ischemic heart disease, cardiac allograft vasculopathy, diabetes, hypercholesterolemia, and smoking. At the level of the myocardial microcirculation, reperfusion injury manifests itself as endothelial dysfunction, no-reflow, and increased permeability, which are all probably the result of reperfusion-induced augmentation of the inflammatory response. In other animal models of cardiovascular disease, inflammatory alterations have been described that can contribute to microvascular endothelial dysfunction and reactive oxygen species, neutrophils, tumour necrosis factor-alpha, and inducible NO synthase are among the mediators that have been incriminated. Circulating levels of inflammatory mediators may serve as molecular markers of cardiovascular disease, and antiinflammatory interventions hold some promise for future cardiovascular therapy. PMID- 9990526 TI - Control of microvascular resistance in physiological conditions and reperfusion. AB - Regulation of coronary microvascular resistance is not distributed uniformly, but varies across different segments of the vasculature. Differences in regulatory mechanisms, including metabolic, myogenic, alpha-adrenergic and endothelial cell mediated, help define a series of coronary vascular microdomains. Generally, small arterioles, those less than 100 microns in diameter, respond differently than large arterioles or small arteries. This segmental distribution suggests an integrative hypothesis of regulation whereby a variety of mechanisms play a role in the overall response. One pathology that disturbs these control mechanisms in the microcirculation of the heart is reperfusion injury. Reperfusion injury of the microcirculation has as its primary target the vascular endothelium. The mechanisms responsible for reduced endothelium-dependent relaxation, likely include a reduction in the levels of tetrahydrobiopterin, a co-factor of nitric oxide synthase. Manipulation of levels of tetrahydrobiopterin in endothelial cells may be beneficial in the prevention of the pathophysiological sequelae of reperfusion injury in the coronary microcirculation. PMID- 9990528 TI - Effects of a metalloproteinase that truncates P-selectin glycoprotein ligand on neutrophil-induced cardiac dysfunction in ischemia/reperfusion. AB - This study was designed to test the effects of polymorphonuclear leukocytes (PMNs) in the presence and absence of a P-selectin blocker, mocarhagin, in provoking cardiac dysfunction in isolated perfused rat hearts following ischemia and reperfusion. Control rat hearts not subjected to ischemia were perfused without blood cells for 80 min. Additional control rat hearts were perfused with 100 x 10(6) PMNs in the presence and absence of 0.2 microgram/ml mocarhagin over a 5-min perfusion followed by a 45-min observation period. No significant reduction in coronary flow (CF), left ventricular developed pressure (LVDP), or the first derivative of LVDP (dP/dt max) was observed at the end of the observation period in any non-ischemic group. Similarly, global ischemia (I) for 20 min followed by 45 min of reperfusion (R) produced no sustained effects on the final recovery of any of these parameters in any group of hearts perfused in the absence of PMNs. I/R hearts perfused with PMNs exhibited decreases of 50-60% in all measurements of cardiac function (P < 0.001). These PMN perfused I/R hearts also exhibited marked increases in cardiac myeloperoxidase (MPO) activity indicating a significant PMN infiltration, and enhanced P-selection expression on the coronary microvascular endothelium. All cardiodynamic effects as well as MPO accumulation and PMN infiltration were attenuated markedly by the metalloproteinase, mocarhagin, which inhibits P-selectin-mediated cell adhesion by cleaving its high-affinity receptor, PSGL-1, present on neutrophils. These results provide evidence that neutrophils provoke post-reperfusion cardiac dysfunction, and that this may be largely due to P-selectin-induced adherence of neutrophils to the endothelium. PMID- 9990529 TI - Cytokines and the microcirculation in ischemia and reperfusion. AB - The intense inflammatory reaction following reperfusion of the infarcted myocardium has been implicated as a factor in extension of injury. However, this inflammatory reaction is also critical to tissue repair. The cellular responses that mediate these functions are orchestrated by sequential induction and/or release of cytokines resulting in a closely regulated cytokine cascade. This paper reviews research on these cytokine cascades, their cellular origin, and factors which control the cellular response to their presence. Factors examined include leukotaxis, phenotypic transition of leukocytes, adhesion molecule induction and the role of cytokines in tissue repair and scar formation. PMID- 9990530 TI - Genistein inhibits slow component delayed-rectifier K currents via a tyrosine kinase-independent pathway. AB - In single guinea pig ventricular cells, genistein, a potent inhibitor of protein tyrosine kinase (PTK), was found to suppress the delayed-rectifier K (IK) current. The present study was carried out to examine the underlying mechanism. Ventricular myocytes were voltage-clamped in the conventional whole-cell mode (36 degrees C). The amplitudes of tail and steady-state (2-s pulse) currents were measured as IK. Genistein (10-100 microM) reversibly inhibited both basal and intrapipette cAMP (1 mM)-enhanced IK currents in a concentration-dependent manner with a half-maximum inhibitory concentration (IC50) at approximately 30 microM. In contrast, lavendustin A (10 microM; n = 5) and tyrphostin 51 (100 microM; n = 5) had no effect on the currents. The inhibitory action of genistein was also seen after IK currents were activated by forskolin (500 nM) plus intrapipette orthovanadate (500 microM). The intrapipette cAMP-enhanced IK was also reduced to a lesser degree by daidzein, an inactive analogue of genistein. Envelope tail and short pulse protocols revealed that genistein inhibits the slow component of IK (IKs). Thus, the inhibitory action of genistein is not mediated via an inhibition of PTK but may be due to the block of IKs channels. PMID- 9990531 TI - Tonic regulation of excitation-contraction coupling by basal protein kinase C activity in isolated cardiac myocytes. AB - A high-speed imaging technique was used to investigate the effects of inhibitors and activators of protein kinase C (PKC) on the [Ca2+]i transients and contraction of fura-2 loaded rat ventricular cardiac myocytes. The amplitude of the [Ca2+]i transient was reduced following treatment with 100 nM phorbol 12,13 dibutyrate (PDBu), whereas the PKC inhibitors staurosporine (0.5 microM) and calphostin C (10 microM) increased [Ca2+]i transient amplitude, elevated basal [Ca2+]i and slowed the decay of the [Ca2+]i transient. These changes were paralleled by similar alterations in the rate and extent of cell shortening. The activity of nitrendipine-sensitive Ca2+ channels was monitored indirectly as the rate of Mn2+ quench of cytosolic fura-2 in electrically-paced cells. PDBu reduced Mn2+ influx by six-fold, whereas staurosporine and calphostin C increased the influx rate by eight-fold and seven-fold over basal quench, respectively. The caffeine releasable Ca2+ pool was reduced in the presence of PDBu and increased transiently in presence of staurosporine. The effects of PKC activation and inhibition on sarcoplasmic reticulum Ca2+ content may be secondary to alterations of sarcolemmal Ca2+ influx. However, the PKC inhibitors also decreased the rate of sarcoplasmic reticulum Ca2+ uptake in permeabilized myocytes, suggesting that a direct effect of PKC on the sarcoplasmic reticulum may contribute to the prolongation of the [Ca2+]i transient under these conditions. The present work demonstrates that basal PKC activity has a potent depressant effect, mediated primarily through inhibition of sarcolemmal Ca2+ influx, which may play a key role in setting the basal tone of cardiac muscle. PMID- 9990532 TI - Comparison of the effects of ORG 30029, dobutamine and high perfusate calcium on function and metabolism in rat heart. AB - Cardiac contractility may be enhanced via multiple cellular mechanisms resulting in varied effects on cardiac energetics. The mechanisms that account for the varied energetic responses are not well understood. The purpose of this investigation was to compare the effects of the calcium sensitizing agent ORG 30029 (N-hydroxy-5,6-dimethoxy-benzo[b]thiophene-2-carboximidamide hydrochloride, a calcium sensitizing agent which increases contractility without increasing calcium transients significantly), dobutamine and high perfusate calcium on contractility and energetics. Langendorff-perfused rat hearts were stimulated with ORG 30029, dobutamine and high perfusate calcium in graduated concentrations while myocardial oxygen consumption (MVO2) and force-time integral were measured. ORG 30029, dobutamine and high perfusate calcium increased contractility in a dose-dependent manner. Despite an increase of 50% in systolic pressure and a 17% increase in force-time integral from control, ORG 30029 had no significant effect on MVO2 at the lower concentrations (n = 6). However, dobutamine (n = 4) and high perfusate calcium (n = 4) caused a 65% increase in systolic pressure and a 17% increase in force-time integral and a 50% and 41% increase in MVO2 respectively (P < 0.05). High energy phosphates (by 31P NMR), and lactate production were unaltered by these agents, suggesting that metabolism was steady state. Basal metabolism tended to increase slightly with dobutamine but not with ORG 30029 or high perfusate calcium. ORG 30029, dobutamine, and high perfusate calcium increase contractility in perfused rat hearts with disparate effects on energetics. These differences may be accounted for, in part, by differences in energy expenditure for calcium handling. PMID- 9990533 TI - KATP channel modulators and myocardial damages induced by ischemia-reperfusion: membrane lipids injury and arrhythmias. AB - Although KATP channels have been proposed as playing a role in most types of myocardial damage associated with ischemia/reperfusion, the potential benefits of KATP channel modulators against the biochemical and electrical disturbances observed during ischemia remain unclear. We have thus studied the effects of glibenclamide and cromakalim, KATP channel blocker and opener respectively, on membrane lipid injury and arrhythmias, in a model of ischemic-reperfused guinea pig myocardium. Ventricular strips were prelabeled with [3H] arachidonic acid, then subjected to normal conditions (Time-related Control) or to simulated ischemic-reperfused conditions in absence of drug (Control) or in presence of glibenclamide 10 microM or cromakalim 10 microM. The release of radioactive compounds was counted by liquid scintillation spectrometry, while action potentials (AP) were recorded with intracellular microelectrodes. Reperfusion induced a significant increase of arachidonic acid release (P < 0.05 versus Time related Control). Glibenclamide inhibited the reperfusion-induced arachidonic acid release while cromakalim only delayed it (respectively 483 +/- 87 dpm/g, P < 0.05 and 790 +/- 143 dpm/g. NS versus 838 +/- 80 dpm/g for Control, after 30 min of reperfusion). Unlike glibenclamide, cromakalim was proarrhythmic during reperfusion (in 100% of preparations versus 33% in Control or in presence of glibenclamide, P < 0.05). This in vitro study shows that glibenclamide prevented the reperfusion-induced membrane arachidonic acid release, without proarrhythmic effect, whereas cromakalim, associated with proarrhythmicity, was unable to protect myocardium from cell lipid damage. PMID- 9990534 TI - B-type Ca2+ channels activated by chlorpromazine and free radicals in membrane of human atrial myocytes. AB - The present study demonstrates that background or B-type calcium channel activity can be recorded in excised inside-out and cell-attached membrane patches from human atrial myocytes. In control conditions, with Ba2+ or Ca2+ as charge carrier, single-channel activity spontaneously appeared in irregular bursts separated by quiescent periods of 2-17 min, in nearly 25% of tested patches. Channel activity was recorded at steady-state applied membrane potentials including the entire range of physiological values, and displayed no "rundown" in excised patches. During activity, a variety of kinetic behaviors could be observed with more or less complex gating patterns. This type of channel activity was triggered or markedly increased when chlorpromazine (CPZ 20 or 50 microM) was applied to internal face of inside-out patches, with a proportion of active patches of approximately 25%. CPZ-activated channels were potential-independent in the physiological range of membrane potential. In 96 mM Ba2+ solution, three conductance levels: 23, 42 and 85 pS were routinely observed in the same excised membrane patch, sometimes combining to give a larger level. As previously observed by Wang et al. (1995) in membrane of rat ventricular myocytes, increasing free-radicals level and metabolic poisoning readily enhanced B-type channel activity in human atrial myocytes. Application of H2O2 (from 0.1-10 mM) in cell-attached mode induced an activation of Ba2+ permeable channel activity in a dose-dependent manner, with an estimated EC50 of 9.7 mM. In the same type of experiments, 10 mM deoxyglucose also induced similar Ba2+ permeable channel activity. When 500 microM CPZ were applied to myocytes studied in the whole-cell configuration and maintained at a holding potential of -80 mV in the presence of 5 mM external Ca2+, a noticeable inward current could be observed. The mean CPZ activated current density determined from seven myocytes was 0.63 pA/pF. PMID- 9990535 TI - Inhibition of adhesion molecules markedly ameliorates cytokine-induced sustained myocardial dysfunction in dogs in vivo. AB - Adhesion molecules are key molecules for inflammatory cardiovascular diseases and are known to be up-regulated by inflammatory cytokines. However, the role of adhesion molecules in the cytokine-induced myocardial dysfunction in vivo remains unclear. This role was examined in our novel canine model, in which chronic treatment of the heart with IL-1 beta-bound microspheres (MS), but not control MS, causes sustained myocardial dysfunction in vivo. The expression of P-selectin (mRNA and immunoreactivity) was more prominent in the IL-1 beta group than in the control group (treated with control MS alone) after MS injection. The extent of neutrophil infiltration and myocardial myeloperoxidase (MPO) activity were significantly increased in the IL-1 beta group (P < 0.01). Pre-treatment with SLeX-OS (a novel oligosaccharide analog of sialyl LewisX) or PB1.3 (a monoclonal antibody to P-selectin) prevented the myocardial dysfunction and significantly suppressed the neutrophil infiltration and the increase in myocardial MPO activity induced by IL-1 beta (P < 0.01 each). These results indicate that adhesion molecules play an important role in the pathogenesis of the cytokine induced sustained myocardial dysfunction in dogs in vivo. PMID- 9990536 TI - Role of oxygen in limiting respiration in the in situ myocardium. AB - 1H NMR has now detected the proximal histidyl N delta H myoglobin (Mb) signal from the myocardium in situ. Upon ligation of the left anterior descending coronary artery in the rat myocardium, the deoxy Mb signal appears at 78 ppm During dopamine infusion at up to 80 micrograms/kg/min, the heart rate pressure product (RPP) increases by a factor of 2, the phosphocreatine (PCr) decreases by 17%, and the ratio of the change in inorganic phosphate over PCr (delta Pi/PCr) increases by 0.2. However, no deoxy myoglobin signal is detected. Oxygen availability does not appear to limit oxygen consumption nor oxidative phosphorylation under dopamine enhanced work state in myocardium. PMID- 9990537 TI - Endothelin-1 increases susceptibility of isolated rat hearts to ischemia/reperfusion injury by reducing coronary flow. AB - Endothelin-1 (ET-1) is the most potent vasoconstrictor known to date, and it was proposed that this peptide plays a major role in myocardial ischemia/reperfusion injury. ET-1 could increase myocardial susceptibility to ischemia by two mechanisms: via coronary flow reduction and/or via direct, metabolic effects on the heart. In isolated, buffer-perfused rat hearts, function was measured with a left ventricular balloon, and energy metabolism (ATP, phosphocreatine, inorganic phosphate, intracellular pH) was estimated by 31NMR-spectroscopy. Under constant pressure perfusion, hearts were subjected to 15 min of control perfusion, 15 ("moderate injury") or 30 ("severe injury") min of global ischemia, followed by 30 min of reperfusion. Hearts were pre-treated with ET-1 (boluses of 0.04, 4, 40 of 400 pmol) 5 min prior to ischemia. In the control period, ET-1 reduced coronary flow, ventricular function, phosphocreatine and intracellular pH dose dependently: during ischemia/reperfusion, coronary flow, functional recovery and high-energy phosphate metabolism were adversely affected by ET-1 in a dose related manner. To study effects of ET-1 not related to coronary flow reduction, additional hearts were perfused under constant flow conditions (ET-1 0 or 400 pmol) during 15 min of control, 15 min of ischemia and 30 min of reperfusion. When coronary flow was held constant, functional and energetic parameters were similar for untreated and ET-1 treated hearts during the entire protocol, i.e. the adverse effects of ET-1 on function and energy metabolism during ischemia/reperfusion were completely abolished. In both constant pressure and constant flow protocols, 400 pmol ET-1 reduced the extent of ischemic intracellular acidosis. The authors conclude that ET-1 increases the susceptibility of isolated hearts to ischemia/reperfusion injury via reduction of coronary flow. PMID- 9990538 TI - Non-anticoagulant heparin increases endothelial nitric oxide synthase activity: role of inhibitory guanine nucleotide proteins. AB - Heparin, which is widely used clinically, has recently been shown to have specific properties affecting the vascular endothelium. We hypothesized that heparin stimulates endothelial nitric oxide synthase (eNOS) activity by a mechanism independent of its anticoagulant properties and dependent on an inhibitory guanine nucleotide regulatory protein (Gi). We determined the effect of both heparin and N-acetyl heparin (Non-Hep), a heparin derivative without anticoagulant properties, on eNOS activity in cultured bovine aortic endothelial cells and on endothelium-dependent relaxation in isolated vascular rings. The eNOS activity was determined by measuring both citrulline and nitric oxide (NO) metabolite formation. Heparin and Non-Hep dose-dependently increased basal eNOS activity (ED50 1.0 microgram/ml or 0.15 U/ml), an effect that was significantly inhibited by pertussis toxin (100 ng/ml), a Gi-protein inhibitor. Agonist stimulated (acetylcholine, 10 microM) eNOS activity was potentiated following pre treatment with both heparin and Non-Hep and reversed by pertussis toxin. Heparin and Non-Hep induced a dose-dependent relaxation in preconstricted thoracic aortic rings, an effect that was significantly inhibited by pertussis toxin, endothelial inactivation (following treatment with sodium deoxycholate) and NG-nitro-L arginine-methyl ester (L-NAME). We conclude that heparin and non-anticoagulant heparin induce endothelium-dependent relaxation following activation of eNOS by a mechanism involving a Gi-protein. Administration of heparin derivatives without anticoagulant properties may have therapeutic implications for the preservation of eNOS in conditions characterized by endothelial dysfunction. PMID- 9990539 TI - Sub-antihypertensive doses of ramipril normalize sarcoplasmic reticulum calcium ATPase expression and function following cardiac hypertrophy in rats. AB - We examined the hypothesis that the angiotensin converting enzyme inhibitor ramipril at sub-antihypertensive concentrations could improve sarcoplasmic reticulum (SR) CaATPase expression and function in compensated hypertrophied rat hearts. Five weeks after abdominal aortic constriction, rats received a daily dose (50 micrograms/kg/day) of ramipril or vehicle for 4 weeks. Cardiac angiotensin-converting enzyme (ACE) activity increased with cardiac hypertrophy (CH) but returned to normal following ramipril treatment. SR CaATPase protein levels and activity decreased with CH (P < 0.05) and were normalized following ramipril treatment (P < 0.05 for protein and activity). No change in phospholamban (PLB) protein levels could be demonstrated between any of the groups. In contrast, ramipril treatment specifically increased control SR CaATPase and PLB mRNA levels by > 60% (P < 0.01) and > 30%, respectively. In the hypertrophied group, SR CaATPase increased by 35% (P < 0.05 n = 6) after ramipril treatment. Calsequestrin mRNA levels were unaffected by ramipril administration. In conclusion, ramipril normalizes SR CaATPase protein expression and function in pressure-overloaded and compensated CH. The effects of ramipril are however multifaceted, affecting RNA and protein expression differentially. PMID- 9990540 TI - FGF-2-induced negative inotropism and cardioprotection are inhibited by chelerythrine: involvement of sarcolemmal calcium-independent protein kinase C. AB - Fibroblast growth factor-2 (FGF-2), administered to the isolated rat heart by perfusion and under constant pressure, is protective against ischemia-reperfusion (I-R). Here we have investigated whether FGF-2 cardioprotection: (a) is dependent on flow modulation; (b) is linked to effects on contractility; (c) is mediated by protein kinase C (PKC); and (d) is linked to PKC and/or mitogen activated protein kinase (MAPK) associated with the sarcolemma. The isolated rat heart was used as a model. Under conditions of constant flow FGF-2 induced significant improvement in recovery of contractile function during I-R. Under constant perfusion pressure, FGF-2 induced a negative inotropic effect (15% decrease in developed pressure). Chelerythrine, a specific PKC inhibitor, prevented both the FGF-2 induced negative inotropic effect before ischemia, and cardioprotection during I R. FGF-2 induced a chelerythrine-preventable, five-fold increase in sarcolemmal calcium-independent PKC activity. It also increased the association of PKC subtypes -epsilon and -delta with sarcolemmal membranes, detected by Western blotting, as well as, for PKC delta, by immunolocalization. FGF-2 increased the association of PKC epsilon with the membrane fraction of adult cardiomyocyte in culture, confirming that it can affect PKC signaling in cardiomyocytes directly and in a manner similar to its effects in situ. Finally, FGF-2 induced increased active MAPK at sarcolemmal as well as cytosolic sites. Active sarcolemmal MAPK remained elevated when the FGF-2-induced protection was prevented by chelerythrine. In conclusion, we have provided evidence that cardioprotection by FGF-2 is independent of flow modulation. PKC activation mediates both the FGF-2 induced negative inotropic effect before ischemia and the cardioprotective effect assessed during reperfusion, suggesting a cause and effect relationship. Furthermore, FGF-2 cardioprotection is linked to targeting of sarcolemmal sites by calcium-independent PKC. PMID- 9990541 TI - Sarcoplasmic reticulum function in murine ventricular myocytes overexpressing SR CaATPase. AB - To examine the effects of the overexpression of sarcoplasmic reticulum (SR) CaATPase on function of the SR and Ca2+ homeostasis, we measured [Ca2+]i transients (fluo-3), and L-type Ca2+ currents (ICa.L), Na/Ca exchanger currents (INa/Ca), and SR Ca2+ content with voltage clamp in ventricular myocytes isolated from wild type (WT) mice and transgenic (SRTG) mice. The amplitude of [Ca2+]i transients was insignificantly increased in SRTG myocytes, while the diastolic [Ca2+]i tended to be lower. The initial and terminal declines of [Ca2+]i transients were significantly accelerated in SRTG myocytes, implying a functional upregulation of the SR CaATPase. We examined the functional contribution of only the SR CaATPase to the initial and the terminal phase of the decline of [Ca2+]i, by abruptly inhibiting Na/Ca exchange with a rapid switcher device. The rate of [Ca2+] decline mediated by the SR CaATPase was increased by 40% in SRTG compared with WT myocytes. The function of the L-type Ca2+ channel was unchanged in SRTG myocytes, while INa/Ca density was slightly (10%) decreased. Measured SR Ca2+ content was significantly increased by 29% in SRTG myocytes. Thus, overexpression of SR CaATPase markedly accelerates the decline of [Ca2+]i transients, and induces in increase in SR Ca2+ content, with some downregulation of the Na/Ca exchanger. PMID- 9990542 TI - Impact of resting and ischemic blood flow on infarct probability in ischemic preconditioning--a new approach to infarct size-blood flow data by logistic regression. AB - The linear regression analysis of infarct size (IS) v ischemic myocardial blood flow (MBF) does not account for the heterogeneity of MBF and infarcted tissue; moreover, it cannot assess a blood flow threshold for infarction (MBFT) accurately, as with ischemic preconditioning (IP) the close relationship between ischemic MBF and IS otherwise observed is lost. Finally, the impact of resting blood flow on myocardial infarction cannot be considered in such analysis. Therefore, in a retrospective data analysis of 32 enflurane-anaesthetized swine undergoing 90 min severe ischemia and 120 min reperfusion without (CON, n = 12) or with IP induced by either 3 (IP3, n = 8) or 10 min ischemia (IP10, n = 12) and 15 min reperfusion, a MBFT was assessed by logistic regression (LR) in individual tissue pieces. MBFT was arbitrarily defined as that ischemic MBF (microspheres) at which infarct probability was 0.2, derived from the ratio of infarcted (n = 141, TTC) to all tissue samples (n = 684). The duration of the preconditioning ischemia and MBF both at rest and during the sustained ischemia were significant predictors of infarct probability. Ischemic MBFT at an infarct probability of 0.2, was 0.089 +/- 0.023 ml/min/g in CON. MBFT was decreased to 0.051 +/- 0.03 ml/min/g with IP3 (P < 0.05 v CON) and further to 0.004 +/- 0.037 ml/min/g with IP10 (P < 0.05 v CON, IP3). Corresponding to the leftward shift of MBFT, the relationships between infarct probability and MBF were shifted in parallel by IP with no change in their slopes. PMID- 9990543 TI - Dual effect of nitric oxide on the hyperpolarization-activated inward current (I(f)) in sino-atrial node cells of the rabbit. AB - Using the whole-cell voltage-clamp technique, we have investigated the effect of nitric oxide (NO) donor (sodium nitroprusside, SNP) on hyperpolarization activated inward current, I(f), in isolated rabbit sinoatrial node (SAN) cells. I(f) in the basal state increased when NO was applied but decreased when I(f) was pre-stimulated by isoproterenol (ISO) or by adding cAMP to the pipette solution. Both the stimulatory and the inhibitory effects of NO were abolished by guanylyl cyclase inhibitor, methylene blue (MB), suggesting that the effect of NO is mediated by cGMP. The inhibitory effect of NO was abolished when I(f) was pre stimulated by 3-isobutyl-1-methylxanthine (IBMX), which is a phosphodiesterase (PDE) inhibitor, or by adding 8Br-cAMP (which is resistant to PDE) to the pipette solution. An analogue of cGMP, 8Br-cGMP, which is a potent stimulator of cGMP dependent protein kinase (PKG) but has little effect on PDE, did not inhibit I(f) when I(f) was pre-stimulated by ISO. In its basal state, I(f) was still increased by 8Br-cGMP, and this effect was not prevented by the pretreatment with H-7, PKG inhibitor. The effect of acetylcholine (ACh) was not identical to that of NO: I(f) decreased when pre-stimulated not only by ISO, but also by IBMX. The above results suggest that via cGMP, NO exerts a dual effect on I(f): the inhibitory effect is mediated by cGMP-stimulated PDE, and the stimulatory effect may be attributable to direct binding of cGMP to I(f) channels. PMID- 9990544 TI - Heat shock provides delayed protection against oxidative injury in cultured human umbilical vein endothelial cells. AB - During both mild and severe ischemia, vascular endothelial cells lining large and small vessels of the ischemic organ are exposed to oxygen-derived free radicals resulting in oxidative damage to the organ. Heat shock has been shown to induce thermotolerance and also protect against ischemic injury, possibly via increased synthesis of heat shock proteins (HSPs). We hypothesized that heat shock preconditioning may protect human endothelial cells against oxidative damage. Cultured human umbilical vein endothelial cells (HUVEC) were subjected to heat shock (42 degrees C, 1 h) and allowed to recover for 2 or 20 h, at which times the cells were oxidatively stressed for 1 h by exposing them to 100-200 mumol/l of hydrogen peroxide (H2O2). Cellular damage was assessed immediately and 18 h later by morphology and release of lactate dehydrogenase (LDH). No protection of HUVEC was seen using the 2-hour recovery interval, but a significant protection (P < 0.05) was observed after the 20-hour delay. Northern blot analysis at 1 and 2 h after heating showed induction of HSP-70 mRNA. Western blot analysis demonstrated a significant increase in HSP-72 protein after 2 as well as 20 h of recovery from heat shock, although the amounts of protein at the two times were not significantly different. Furthermore, no differences in the activity of the antioxidant enzyme catalase were observed between heated and unheated HUVEC at 2 and 20 h after heat preconditioning. Thus, heat shock preconditioning induces delayed protection against oxidative injury in HUVEC, and the mechanism of protection appears to involve more than the expression of HSP-72 or activity of catalase. PMID- 9990545 TI - Characterization of the high affinity [3H]nociceptin binding site in membrane preparations of rat heart: correlations with the non-opioid dynorphin binding site. AB - The binding parameters of [3H]nociceptin were examined in membrane preparations of rat heart and compared with those of [3H]dynorphin A-(1-13) ([3H]Dyn A-(1 13)). Scatchard analysis of [3H]nociceptin binding revealed the presence of two distinct sites: a high affinity (Kd: 583 nM) low capacity (Bmax: 132 pmol/mg protein) site and a low affinity (Kd: 10,316 nM) high capacity (1552 pmol/mg protein) site. Dyn A and related peptides were potent competitors of the binding to the high affinity site with the following rank order of potency: alpha-neo endorphin > Dyn A-(2-13) = Dyn A-(3-13) > Dyn A-(5-13) > Dyn A-(1-13) > Dyn A > Dyn B > Dyn A-(6-10) >> Dyn A-(1-8). Nociceptin was 6.7 times less potent than Dyn A with a Ki of 4.8 microM as compared with 0.72 microM for Dyn A. The order of potency of the various peptides in inhibiting [3H]nociceptin binding correlated well (r = 0.93) with their ability to complete with the binding of [3H]Dyn A-(1-13) (Dumont and Lemaire, 1993). In addition, the high affinity [3H]nociceptin and non-opioid [3H]Dyn A-(1-13) sites were both sensitive to NaCl (120 mM) and the phospholipase C (PLC) inhibitors, U-73122 and neomycin (100 microM). The binding activities were less affected by the weak PLC inhibitor, U 73343, and no effect was observed with the non-hydrolysable GTP analogs. Gpp(NH)p and GTP-gamma-S. Nociceptin (1-50 microM) was also shown to inhibit the uptake of [3H]noradrenaline ([3H]NA) by cardiac synaptosomal preparations. In spontaneously hypertensive rats (SHR), the potency of nociceptin in inhibiting [3H]NA uptake was increased by 1.6-fold as compared with Wistar Kyoto (WKY) control rats and such effect was accompanied by comparable increased levels of cardiac ORL1 mRNA and [3H]nociceptin high affinity sites. These changes correlated well with the previously observed increased levels of non-opioid cardiac [3H]Dyn A-(1-13) sites in SHR (1.3 times as compared with WKY) and increased potency of Dyn A-(1-13) in inhibiting [3H]NA uptake by cardiac synaptosomes in SHR (2.2-fold as compared with WKY) (Dumont and Lemaire, 1995). The results demonstrate that in rat heart the characteristics of the high affinity, low capacity [3H]nociceptin binding site are similar to those of the non-opioid Dyn binding site. The stimulation of this site by nociceptin, Dyn A or related peptides is more likely to produce a modulation of PLC activity and [3H]NA uptake and may participate to the pathophysiology of hypertension. PMID- 9990546 TI - LPS-induced TNF-alpha release from and apoptosis in rat cardiomyocytes: obligatory role for CD14 in mediating the LPS response. AB - The bacterial endotoxin lipopolysaccharide (LPS) contributes to the cardiovascular collapse and death observed in patients with sepsis. Because LPS has such profound effects on cardiac performance, we speculate that direct effects of LPS could be demonstrated on cardiomyocytes in culture, and that these direct effects are mediated by the LPS receptor, CD14. Accordingly, in this study, we provide evidence for CD14-dependent cardiotoxic effects of LPS including the LPS-stimulated secretion of tumor necrosis factor alpha (TNF-alpha) from cardiomyocytes. TNF-alpha is an inflammatory cytokine which is known for its negative inotropic effects on cardiac performance, but has not until recently been shown to be produced by cardiac cells. In this study, LPS was found to stimulate strongly in a dose-dependent manner the secretion of TNF-alpha from cultured adult rat cardiomyocytes. Further, LPS-induced TNF-alpha secretion was blocked by an inhibitor of TNF-alpha processing, metallomatrix protease inhibitor (TAPI). Molecular and immunological evidence demonstrated the presence of LPS receptors (CD14) on cardiomyocytes. Attenuated TNF-alpha secretion following PI PLC treatment confirmed the functional importance of CD14 for LPS-mediated myocardial effects. Importantly, LPS also triggered apoptosis in cultured cardiomyocytes as quantified by single-cell gel electrophoresis of nuclei exhibiting DNA fragmentation patterns characteristic of apoptosis (i.e. cardiac comets). Apoptotic cell death was blocked by pre-incubation with the soluble TNF alpha receptor fragment (TNFRII:Fc), suggesting that LPS-induced apoptosis was TNF-alpha-dependent and probably involved an autocrine function for the TNF-alpha whose secretion was under LPS control. The results of this study suggest that the cardiodepressant effects of LPS are dependent on CD14 signaling and may not only be due to acute negative inotropic effects of TNF-alpha but also may be complicated by TNF-alpha-induced apoptotic cell death which effectively reduces the number of working myocardial cells. PMID- 9990548 TI - An alternative preconditioning mechanism? PMID- 9990547 TI - Fluorescent phalloidin enables visualization of actin without effects on myosin's actin filament sliding velocity and hydrolytic properties in vitro. AB - Recent reports have demonstrated an activating effect of phalloidin in striated muscle. Furthermore, modeling of X-ray diffraction and crystallographic data suggests that phalloidin binding may induce conformational changes in actin. To determine whether phalloidin affects the mechanics of the actomyosin interaction, the velocity of actin filaments variably labeled with rhodamine-phalloidin was measured. In addition, solution actin-activated myosin subfragment-1 ATPase activity with phalloidin-labeled actin was compared to unlabeled actin. Here we found that phalloidin does not significantly effect actin filament velocity or parameters of ATPase, namely Vmax and K(m). Possible differences between muscle strip data and these in vitro results are discussed. PMID- 9990549 TI - What's new in neuropsychiatry. PMID- 9990550 TI - Neuropsychiatric presentation of multiple sclerosis. PMID- 9990551 TI - The American Neuropsychiatric Association: ten years of progress and a future of great promise. AB - The author reviews the history, accomplishments, and goals of the American Neuropsychiatric Association on the occasion of the tenth anniversary of its founding. PMID- 9990552 TI - The neurobiology and pharmacotherapy of Alzheimer's disease. AB - Alzheimer's disease (AD), the most common cause of dementia, has become a major public health concern as our population ages. In recent years, AD has attracted the attention of a wide range of biological disciplines, and substantial progress has been made in understanding the mechanisms of neurodegeneration in AD. Four different genes have now been associated with AD and are providing insights into the pathogenesis of the disease. The roles of beta-amyloid, tau, hormonal changes, inflammation, and oxidative stress in the neurodegeneration of AD are also being delineated. Based on these discoveries, rational therapeutic strategies are developing rapidly. The authors review these and other recent advances in the neurobiology and pharmacotherapy of AD. PMID- 9990553 TI - Safety and efficacy of ECT in patients with head injury: a case series. AB - Electroconvulsive therapy (ECT) is a safe and effective treatment for certain psychiatric disorders. Eleven patients who had sustained a closed head injury were treated with ECT for their psychiatric symptoms. Eight patients responded to an index course of ECT: 2 were partial responders and became responders during continuation ECT (cECT); 1 patient was a nonresponder. Post-ECT Neurobehavioral Cognitive Status Examination and Mini-Mental State Examination scores showed no significant decline (P > 0.70 and P > 0.89, respectively) from baseline. Eight patients received cECT, without any lasting cognitive side effects. These findings indicate that ECT can be used effectively in patients with a history of closed head injury, without adverse effects on cognitive functioning. PMID- 9990554 TI - Cognitive and behavioral sequelae of closed head injury in older adults according to their significant others. AB - This study examined the neurobehavioral effects of closed head injury (CHI) in older adults according to their significant others. Informants of 17 mild and moderate CHI patients > or = 50 years old when injured completed the Geriatric Evaluation of Relative's Rating Instrument, a questionnaire inquiring about the patient's cognition, affect, interpersonal relations, and daily activities. The significant others provided retrospective ratings of preinjury functioning and completed the same instrument an average of 4 and 13 months post-injury. The significant others of 10 community-residing, normal control subjects completed the questionnaire at comparable intervals between each rating. Compared with their preinjury functioning, and unlike the control subjects, patients showed declines in cognition and mood. The possible impact of these changes, including their effect on subjective burden in caregivers, is discussed. PMID- 9990555 TI - Correlates of executive function in multiple sclerosis: the use of magnetic resonance spectroscopy as an index of focal pathology. AB - Proton magnetic resonance spectroscopy (MRS) was performed in a group of patients with multiple sclerosis (MS) and matched control subjects to examine the relationship between frontal lobe pathology and performance on tests of executive function. The N-acetyl aspartate/creatine ratio (NAA/Cr) was significantly reduced in frontal lesions and/or normal-appearing white matter in the patient group compared with the control group, but choline/creatine ratios did not differ. Although MRS abnormalities and executive deficits were not correlated for MS patients as a group, a few patients with more severe abnormalities of NAA/Cr ratio performed worse than other patients on the spatial working memory test, suggesting that subtle frontal neuropathological abnormalities detected by MRS may contribute to executive deficits. Further investigation is warranted to determine the value of MRS as an index of the pathophysiological processes leading to cognitive deficit. PMID- 9990556 TI - Neuropsychiatric manifestations of multiple sclerosis. AB - The range of neuropsychiatric symptoms in multiple sclerosis (MS) has not been prospectively assessed. The authors, working at a tertiary medical center in Mexico City, used the Neuropsychiatric Inventory (NPI) to evaluate neuropsychiatric symptoms prospectively in 44 MS patients who were stable between relapses and 25 control subjects of similar age, education, and cognitive function. Neuropsychiatric symptoms were present in 95% of patients and 16% of control subjects. Changes present were depressive symptoms (79%), agitation (40%), anxiety (37%), irritability (35%), apathy (20%), euphoria (13%), disinhibition (13%), hallucinations (10%), aberrant motor behavior (9%), and delusions (7%). The only relationships with MRI were between euphoria and hallucinations and moderately severe MRI abnormalities. The authors conclude that diverse types of neuropsychiatric symptoms are common in MS; symptoms are present between exacerbations; and there are variable correlations with MRI abnormalities. PMID- 9990557 TI - Neurophysiological aspects of synesthetic experience. AB - Synesthesia is a perceptual condition in which stimulation in one sensory modality elicits a concurrent sensation in another. The authors studied possible electrophysiological correlates of synesthetic experience in 17 subjects claiming to continuously experience chromatic-graphemical synesthesia and a matched control group. Subjects had to respond to one of four numbers and one of six letters by pressing a button. Even-related potentials (ERPs) were recorded from multiple scalp sites. Most synesthetic subjects reported strong synesthetic perceptions during the experiment. The ERPs of both groups showed a distinct P300 component when subjects encountered the assigned target number or letter. Synesthetic subjects had significantly and clearly more positive waveform over frontal and prefrontal scalp regions than control subjects for target and nontarget stimuli. This electrophysiological marker is discussed in terms of cortical inhibition in synesthetic subjects and the role of prefrontal regions in multisensory integration. PMID- 9990558 TI - Lack of effect of apolipoprotein E E4 allele on neuropsychiatric manifestations in Alzheimer's disease. AB - The association between the apolipoprotein E epsilon 4 (APOE E4) allele and a wide spectrum of behavioral symptoms of Alzheimer's disease (AD) was investigated. Neither the severity nor the presence of any behavioral changes was associated with the number of APOE E4 alleles, even after controlling for the effects of age at onset, sex, education level, duration of illness, and severity of dementia. The findings do not support the hypothesis that neuropsychiatric manifestations of AD are different in patients with the APOE E4 allele. PMID- 9990559 TI - Reduced volume of limbic system-affiliated basal ganglia in mood disorders: preliminary data from a postmortem study. AB - Volumes of basal ganglia in postmortem brains of 8 patients with mood disorders and 8 control subjects without neuropsychiatric disorder were determined. Morphometry of serial whole-brain sections under the control of postmortem artifacts revealed reduced volumes of the left nucleus accumbens (-32%, P = 0.01), the right and left external pallidum (-20%, P = 0.04), and the right putamen (-15%, P = 0.04) in the patient group compared with the control group. These results suggest that, in particular, the limbic loop of the basal ganglia involving the nucleus accumbens and the pallidum is affected in mood disorders. PMID- 9990560 TI - Reduction of motoric agitation and restlessness by AF102B and tacrine in the macaque. AB - The cholinesterase inhibitor tacrine (THA) and the M1 muscarinic agonist AF102B (cevimeline), both reported to enhance cognition in animals and humans, were tested in 5 macaques for reduction of spontaneous, random movements. Monkeys were videotaped 1 hour after administration of normal saline vehicle, after low- and high-dose intramuscular AF102B, and after low- and high-dose oral THA. Two independent blind judges counted numbers of spontaneous movements made by each monkey over 12 consecutive 15-second segments for each drug condition. Both THA and AF102B reduced movement significantly at high doses without overt side effects, warranting further research on the agitation-reducing potential of cognition-enhancing cholinomimetic drugs. PMID- 9990561 TI - Clozapine restores water balance in schizophrenic patients with polydipsia hyponatremia syndrome. AB - Hyponatremia/hypoosmolemia causes marked morbidity and prolongs hospital stays in a significant subset of schizophrenic patients. Case reports with methodological limitations suggest clozapine ameliorates this water imbalance. To more conclusively assess this possibility, we completed a 24-week open-label study in 8 male polydipsic hypoosmolemic schizophrenic inpatients. Subjects were treated initially for 6 weeks with a conventional neuroleptic, which was replaced by 300, 600, and 900 (if tolerated) mg/day of clozapine for sequential 6-week periods. On clozapine, mean plasma osmolality rose an average of 15.2 mosm/kg (95% CI: 5.5 25.0). Dosage of 300 mg/day of clozapine was sufficient to normalize plasma osmolality and was generally well tolerated. Clozapine appears to be the first effective pharmacotherapy for severe water imbalance in schizophrenia. PMID- 9990562 TI - Stability of neurological soft signs in chronically hospitalized schizophrenic patients. AB - Neurological soft signs (NSS) have been shown to be more prevalent in chronically ill and in acute or never-mediated patients with schizophrenia. If neurological soft signs are trait-like, then NSS scores should be relatively stable over time and should not be related to changes in patients' psychopathology or medication. Chronically hospitalized patients with schizophrenia were rated two or more times over a 5-year period with standard NSS and psychopathology scales. Total NSS scores were highly correlated over time, and changes in NSS scores at two time points were not significantly related to changes in psychopathology scores. Total NSS scores did not change significantly in a subsample rated when they were first treated with a traditional neuroleptic and later with an atypical neuroleptic. The findings suggest total NSS scores may have some characteristics of a trait like feature in chronically hospitalized patients with schizophrenia. PMID- 9990563 TI - Carbamazepine in the treatment of Lyme disease-induced hyperacusis. AB - Lyme disease-induced hyperacusis can be an intensely disabling, chronic condition that is accompanied by posttraumatic stress disorder-like psychobehavioral sequelae. The authors describe effective treatment of 2 patients with carbamazepine. Speculations regarding a mode of action are offered. PMID- 9990564 TI - Episodically remitting akinetic mutism following subarachnoid hemorrhage. AB - Akinetic mutism is characterized by alertness with near complete absence of volitional activity. The authors report a case of episodically remitting akinetic mutism following subarachnoid hemorrhage. PMID- 9990565 TI - Visual scanning of facial expressions in schizophrenia. AB - The authors previously observed that schizophrenic patients generated fewer fixations of < or = 50.1 ms in response to faces than did a clinical control group. This study examined whether deficits in short-duration eye movements were related to patients' problems in gestalt perception of faces. Faces were presented in upright and inverted orientations to examine the effects of distorting facial gestalts on eye movements. Normal subjects generated more saccades of < or = 50.1 ms to upright than to inverted faces. Patients' saccades of < or = 50.1 ms did not differ between orientations. Patterns of fixations and of saccades > 50.1 ms did not differ between groups. The results may indicate deficits in these patients in search strategies that underlie perception of facial gestalts. PMID- 9990566 TI - Clinicopathologic case report. Dementia with Lewy bodies (DLB). PMID- 9990567 TI - Drug-responsive mania in a man with a brain tumor. PMID- 9990568 TI - Mirtazapine-induced mania in a case of poststroke depression. PMID- 9990569 TI - Anatomic basis of Kluver-Bucy syndrome. PMID- 9990570 TI - Chronic manganism: fourteen years of follow-up. PMID- 9990571 TI - Grand mal seizures with liver toxicity in a case of clozapine treatment. PMID- 9990572 TI - Severe normochrome and normocytic anemia after 19 months on ticlopidine. PMID- 9990573 TI - Determinants of plasma retinol concentrations of middle-aged women in rural China. AB - The purpose of this study was to assess the correlates and possible determinants of plasma vitamin A among middle-aged women in rural China. The vitamin A adequacy of the different diets at the five widely varying survey sites was also assessed. Patterns of correlations among dietary and biochemical measurements were strikingly different from previous studies in Western subjects. Plasma beta carotene was uncorrelated with beta-carotene intake even after adjusting for potential confounders. In counties with low preformed vitamin A intake, plasma retinol correlated with plasma copper (P = 0.007), which in turn was correlated with dietary intake of copper (P = 0.007). In these counties plasma retinol was correlated with plasma beta-carotene (P = 0.001) and was increased 10% in women in the first 2 y of menopause (P = 0.028). Plasma retinol and C-reactive protein levels are inversely correlated (r = -0.15, P < 0.001), indicating that vitamin A status and inflammatory response may be related but the causal direction is unknown. Despite low intake of vitamin A (county averages of 13-78% of recommended daily allowance [RDA]), and particularly of preformed vitamin A, only 3% of these women had plasma retinol levels below 0.7 mumol/L, considered to indicate possible marginal deficiency. Plasma levels of retinol and beta-carotene were more influenced by intrinsic factors such as menopause, lipid status, retinol requirements, and possibly copper status and inflammation than by extrinsic factors such as diet and lifestyle. PMID- 9990574 TI - Randomized clinical outcome study of critically ill patients given glutamine supplemented enteral nutrition. AB - Glutamine is normally an abundant amino acid in the body. It has many important metabolic roles, which may protect or promote tissue integrity and enhance the immune system. Low plasma and tissue levels of glutamine in the critically ill suggest that demand may exceed endogenous supply. A relative deficiency of glutamine could compromise recovery, resulting in prolonged illness and an increase in late mortality, morbidity, and consequently hospital costs. Using a prospective block-randomized, double-blind treatment study design, we tested whether a glutamine-containing enteral feed compared with an isonitrogenous, isoenergetic control feed would influence outcome. The study endpoints were morbidity, mortality, and hospital cost at 6 mo postintervention. In one general intensive care unit (ICU), to ensure consistency of management policies, 78 critically ill adult patients with Acute Physiological and Chronic Health Evaluation (APACHE) II score of 11 and greater and who were considered able to tolerate introduction of enteral nutrition were studied. Fifty patients successfully received enteral nutrition (26 glutamine, 24 control). There was no mortality difference between those patients receiving glutamine-containing enteral feed and the controls. However, there was a significant reduction in the median postintervention ICU and hospital patient costs in the glutamine recipients $23,000 versus $30,900 in the control patients (P = 0.036). For patients given glutamine there was a reduced cost per survivor of 30%. We conclude that in critically ill ICU patients enteral feeds containing glutamine have significant hospital cost benefits. PMID- 9990575 TI - The Mini Nutritional Assessment (MNA) and its use in grading the nutritional state of elderly patients. AB - The Mini Nutritional Assessment (MNA) has recently been designed and validated to provide a single, rapid assessment of nutritional status in elderly patients in outpatient clinics, hospitals, and nursing homes. It has been translated into several languages and validated in many clinics around the world. The MNA test is composed of simple measurements and brief questions that can be completed in about 10 min. Discriminant analysis was used to compare the findings of the MNA with the nutritional status determined by physicians, using the standard extensive nutritional assessment including complete anthropometric, clinical biochemistry, and dietary parameters. The sum of the MNA score distinguishes between elderly patients with: 1) adequate nutritional status, MNA > or = 24; 2) protein-calorie malnutrition, MNA < 17; 3) at risk of malnutrition, MNA between 17 and 23.5. With this scoring, sensitivity was found to be 96%, specificity 98%, and predictive value 97%. The MNA scale was also found to be predictive of mortality and hospital cost. Most important it is possible to identify people at risk for malnutrition, scores between 17 and 23.5, before severe changes in weight or albumin levels occur. These individuals are more likely to have a decrease in caloric intake that can be easily corrected by nutritional intervention. PMID- 9990576 TI - Effect of prolonged intraluminal alpha-amylase inhibition on eating, weight, and the small intestine of rats. AB - Effects of chronic intraluminal amylase inhibition on eating and the digestive system are unclear. In growing rats, we determined the effect of ingesting a wheat amylase inhibitor (AI) on eating, weight, small intestinal mucosal growth, and disaccharidases. Three groups of 12 rats received AI, were pair-fed controls (PFC), or had free access to food (FAC). After measuring food intake and body and stool weight for 21 d, rats were decapitated and the small intestine was divided into four segments. AI and PFC rats had similar food intake, weight gain, and stool output, but these were less than FAC rats (P < 0.005). AI rats ate less (P < 0.001) than PFC during the light cycle and less than FAC rats during darkness. Mucosal DNA and RNA were reduced (P < 0.05) in the upper small intestine of AI and PFC rats compared with FAC rats. Mucosal weight, RNA, and disaccharidase activities were greater (P < 0.01) in the ileum of AI rats compared with PFC and FAC rats. AI alters the amount and pattern of food intake, reduces weight gain, upper small intestinal mucosal weight, protein and DNA, and increases distal small intestinal mucosal weight, RNA, and disaccharidases. AI likely causes these effects by inducing satiety and increasing carbohydrate delivery to the distal intestine. PMID- 9990577 TI - Dietary amino acids as new and novel agents to enhance allograft survival. AB - Dietary supplementation with arginine was previously found to enhance cardiac allograft survival in rats when given with a donor-specific transfusion and a short low-dose course of cyclosporine. This study was performed to determine further the role of amino acid supplementation in prolonging allograft survival. Standard isocaloric, isonitrogenous diets were modified to contain 2 or 4% of energy from arginine, 2 or 4% from glutamine, 4% from glycine or the following combinations: 2% arginine with 2% glutamine, 2% arginine with 4% glutamine, or 1% arginine with 2% glutamine. These diets were started along with a donor-specific transfusion and a 7-d course of cyclosporine the day before cardiac transplantation from an ACI to Lewis strain rat. Median survival times in days for the groups were as follows: control without amino acids, 19.0; 2% arginine, 68.0; 4% arginine, 35.5; 2% glutamine, 28.5; 4% glutamine, 53.5; 4% glycine, 31.5; 2% arginine with 2% glutamine, 39.5; 2% arginine with 4% glutamine, 42.5 and 1% arginine with 2% glutamine, 35.5. Each experimental diet except 2% glutamine and 4% glycine significantly enhanced allograft survival (P < 0.05) with the 2% arginine diet being the best (91.6 +/- 32.3 d [mean +/- SEM] versus 20.1 +/- 3.2 d for control). It is concluded that both arginine and glutamine enhance the immunosuppressive effects of donor-specific transfusion and cyclosporine. PMID- 9990578 TI - Effect of intravenous omega-6 and omega-3 fat emulsions on nitrogen retention and protein kinetics in burned rats. AB - The effect of omega-3 fat emulsion on nitrogen retention and kinetics in relation to fatty acid profile were investigated in burned rats receiving total parenteral nutrition (TPN). A fat emulsion of a structured symmetrical triacylglycerol containing only eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) (2:1) was prepared. Sprague-Dawley rats were fed by fat-free chow for 2 wk. Then rats were fed exclusively with one of three types of TPN for 7 d. Animals in group C received fat-free TPN (n = 11). Group omega 6 received safflower oil fat emulsion, which accounted for 20% of total caloric intake (n = 11). Group omega 3 received fat emulsion containing only EPA and DHA (1% of total calories, n = 11), in addition to safflower oil emulsion (19% of total calories). On day 5, each rat was subjected to 20% full-thickness scald burns. Rats were sacrificed under ether anesthesia 48 h after burning. The rats in group C became deficient in omega-6 essential fatty acids. Cumulative nitrogen balance was decreased significantly in group omega 6. The rates of whole-body protein synthesis were increased significantly in both groups omega 6 and omega 3. In omega 6, however, the rates of whole-body protein breakdown were increased significantly. In conclusion, the rates of whole-body protein breakdown increased and nitrogen retention was aggravated significantly in animals administered the safflower oil emulsion. Significant increases of urinary excretion of total catecholamine were also observed. Prostaglandin E2 and thromboxane B2 concentrations were not significantly different among three groups. Supplementation with the new omega-3 fat emulsion, however, improved protein metabolism in burned rats receiving TPN. PMID- 9990580 TI - Muscle amino acid metabolism and the control of muscle protein turnover in patients with chronic renal failure. AB - Malnutrition is frequently observed in patients with end-stage renal disease. Studies indicate that poor nutritional status plays a major role among factors adversely affecting patients outcome. Therefore prevention and treatment of malnutrition in renal patients is a major issue. In this article the potential mechanisms for alterations in muscle protein metabolism in uremia are explored. Malnutrition has been mainly attributed to inadequate intake of nutrients, superimposed illnesses, or both. However, both clinical and experimental evidence show that uremia per se may adversely affect the control of muscle protein and amino acid metabolism. Available evidence suggests that catabolic factors appear to be distinct for patients at different stages of chronic renal failure and require different modalities of treatments. Both nutritional requirements and the prevalence of malnutrition increase as end-stage renal disease progresses. Muscle protein degradation is increased by metabolic acidosis, which is often found in uremic patients. Another relevant, but less proven cause for increased protein degradation is insulin resistance. Furthermore, specific defects in muscle amino acid metabolism, resistance to growth hormone, insulin-like growth factor 1, or a very low protein intake can reduce muscle protein synthesis. Finally, the hemodialytic procedure per se can stimulate protein breakdown or reduce protein synthesis. All these factors may potentiate the effects of concurrent catabolic illnesses, anorexia, and physical inactivity often found in uremic patients. PMID- 9990579 TI - A vitamin E-deficient diet affects nerve regeneration in rats. AB - Degenerative changes in the neuromuscular system have been found in animals and humans with vitamin E (E) deficiency. This morphologic study examined the effect of dietary E on the regeneration of peripheral nerves in male Sprague-Dawley rats. After feeding an E-sufficient diet (dl-alpha-tocopheryl acetate 50 mg/kg diet) for 6 d, 24 rats were randomly and equally assigned to one of three groups: control (CTRL) fed an E-sufficient diet for 43 d without surgery, normal (NE) fed an E-sufficient diet, or low (LE) fed an E-deficient diet (dl-alpha-tocopheryl acetate 0 mg/kg diet). After 22 d of feeding, NE and LE had surgical compression of the right sciatic nerve and continued eating for 15 d. On day 43, the right triceps surae muscles and a segment of the right sciatic nerve were removed, then all rats were euthanized. The nerve and muscles were processed for morphologic analyses. Presurgery and postsurgery LE ate less food (P < 0.048 and P < 0.001, respectively), which resulted in a lower body weight gain (P < 0.0002). LE had irregularly shaped and less myelinated axons than NE (P < 0.0001) and CTRL (P < 0.0001). The LE plantaris muscle had less type II fibers when compared with NE (P < 0.007) and CTRL (P < 0.03). The results suggest that an E-deficient diet affects food intake, impairs nerve regeneration, and decreases type II fibers, whereas an E-sufficient diet contributes to normal axon regeneration. PMID- 9990581 TI - Possible side effects on vitamin A status due to fiber supplementation in diabetic children. PMID- 9990582 TI - Effect of a chicken egg shell powder enriched dairy product on bone mineral density in persons with osteoporosis or osteopenia. PMID- 9990583 TI - Immunologically enhanced enteral feeds in critical illness. PMID- 9990584 TI - The state of the Mini Nutritional Assessment? PMID- 9990585 TI - Influence of EPA and DHA intravenous fat emulsions on nitrogen retention and protein kinetics in burned rats. PMID- 9990586 TI - Intestinal mucosa versus dietary carcinogens: the carcinogenic consequence of metabolic defense enzyme disruption. PMID- 9990587 TI - Glutathione redox disturbances in human immunodeficiency virus infection: immunologic and therapeutic consequences. PMID- 9990588 TI - The mechanisms of fat malabsorption in cystic fibrosis patients. PMID- 9990589 TI - Growth failure in inflammatory bowel disease. PMID- 9990590 TI - Home parenteral nutrition: the pediatric point of view. PMID- 9990591 TI - Meta-analysis. PMID- 9990592 TI - Relevance of N-acetylcysteine in clinical practice: fact, myth or consequence? PMID- 9990593 TI - Research data: source of information for patient education materials. PMID- 9990594 TI - Appropriate use of the implantable cardioverter defibrillator: a Canadian perspective. Canadian Working Group on Cardiac Pacing. PMID- 9990595 TI - Radiofrequency catheter ablation of symptomatic ventricular ectopic beats originating in the right outflow tract. AB - Ectopic activity originating in the right ventricular outflow tract is a frequent finding and may result in severe symptoms such as dyspnea, palpitations, and lack of physical capacity correlated with a low cardiac output. In 12 consecutive symptomatic and drug refractory patients, we performed a study with intracardiac mapping and ablation procedure. The origin of the ectopic beats was identified, and the ablation procedure was performed. Patients were examined by serial ECG, Holter ECG, bicycle ECG, echocardiography, and thoracic X ray. At baseline, the mean number of ectopic beats was 23,823 during Holter ECG. No other arrhythmias were present. Patients underwent basic electro-physiological study, mapping process, and ablation in a single procedure. Ablation was performed with a deflectable thermocoupled catheter with tip electrodes of 4 mm. Criteria for identification of the origin of the ectopic beats included pace mapping with 12 leads and earliest endocardial activation. One male patient suffered from myocarditis; the other 11 patients had no underlying structural heart disease. The mean age was 38 years. Ablation procedure with delivered temperature of 70 degrees C was successful in 11 of 12 patients eliminating the focus. The mean procedural time was 79 +/- 34 minutes; mean fluoroscopy time was 13.8 +/- 8.8 minutes; and mean number of applications was 4.4 +/- 2.8. No adverse effects occurred during a follow-up period of 10 months after ablation. The mean number of ectopic beats per 24 hours after ablation was 317 +/- 599 with a P value of 0.00024. The clinical symptoms improved in all but one patient. One patient had a recurrence after 2 months that could be successfully treated by a second procedure. In our experience, temperature guided radiofrequency catheter ablation is safe and effective for the treatment of patients with symptomatic ectopic activity of the right outflow tract. As long as we lack the experience of a greater patient cohort and a longer follow-up, only drug resistant and highly symptomatic patients should be selected. PMID- 9990596 TI - Improved efficacy of mode switching during atrial fibrillation using automatic atrial sensitivity adjustment. AB - Automatic mode switching (AMS) during atrial fibrillation (AF) in a dual chamber pacemaker is dependent on the accurate detection of an atrial electrogram. As atrial amplitude is often reduced during AF compared with sinus rhythm, this may result in failure of the AMS and a rapid ventricular response. In addition, undersensing of AF may result in competitive atrial pacing that sustains AF. We hypothesize that the use of automatic atrial sensitivity adjustment (ASA) may enhance AF sensing in a dual chamber pacemaker. We studied the AMS response with and without ASA of the Marathon DDDR (model 294-09, Intermedics, Inc.) pacemaker in 10 patients with paroxysmal AF. Intracardiac atrial electrograms during sinus rhythm and induced AF were recorded onto an analog tape recorder. They were replayed into the pacemaker to assess the AMS response at various starting atrial sensitivities from 3.5 to 0.8 mV with ASA activated and without. Atrial amplitude was reduced during AF. The higher the initial atrial sensitivity, the better is the AMS response and the lower the incidence of AF undersensing. The percentage of AMS before ASA ranged from 2.1% at an atrial sensitivity 3.5 mV to 95.6% at highest sensitivity of 0.5 mV (P < 0.05). After 10 minutes of ASA, the AMS response was improved from 1.7% to 50.6% and from 9.5% to 50.9% at starting atrial sensitivities of 3.5 mV and 2.5 mV, respectively (P < 0.05 in both instances). Undersensing during AF was also significantly reduced after ASA from 70% to 10% at a sensitivity of 3.5 mV and from 33.8% to 10.8% at 2.5 mV. There was no increase in oversensing. In four patients with paroxysmal AF with an implanted pacemaker, ASA improved AMS response in patients with a low implant atrial amplitude. In conclusion, efficacy of mode switching and AF sensing are dependent on the programmed atrial sensitivity, which can be enhanced with the use of ASA, particularly when P wave sensing during AF is borderline. PMID- 9990597 TI - Spinal cord stimulation for the treatment of refractory angina pectoris: a two year follow-up. AB - Twenty-three patients affected by severe, refractory angina were submitted to permanent spinal cord stimulation (SCS) and then followed in our outpatient clinic for 24 months. During the follow-up period, the number of weekly angina episodes drastically dropped from 9.2 (preimplant) to 1.8 in the 3rd, 2.5 in the 6th, 4.5 in the 12th, and 4.2 in the 24th month, with a statistically significant difference (P < 0.01) between the first and last values. A significant increase in the average exercise time from 320 +/- 120 seconds (in baseline condition) to 410 +/- 115 seconds (during SCS) was observed at the treadmill stress test (P < 0.01). SCS was well tolerated by all the patients. However, 7 patients died during follow-up (3 myocardial infarctions, 2 noncardiac deaths, and 2 sudden deaths). Three generators were replaced because of battery depletion after 15, 17, and 21 months. No serious complication was observed. In conclusion, in patients with otherwise intractable angina or already submitted to myocardial revascularization, SCS is very effective in reducing the number of angina episodes. The time of the work during exercise stress test is also significantly prolonged. PMID- 9990598 TI - Atrial ejection force in patients with atrial fibrillation: comparison between DC shock and pharmacological cardioversion. AB - It is well known that the restoration of sinus rhythm is not always associated with the return of effective atrial contraction. Atrial ejection force (AEF) is a noninvasive Doppler derived parameter that measures the strength of the atrial contraction. The aim of the present study was to use pulsed-Doppler echocardiography to determine if different modalities of cardioversion influence the delay in the return of effective atrial contraction after cardioversion. DC shock and pharmacological therapy were compared. Sixty-eight patients were randomly cardioverted, either using DC shock or i.v. procainamide. The patients who were restored to a sinus rhythm had a complete Doppler echocardiographic examination within 1 hour after the restoration, after 24 hours, after 1 month, and after 3 months. AEF was measured and compared in the two groups of patients and within the same group. AEF was greater immediately and at 24 hours after cardioversion in patients who underwent pharmacological therapy compared to patients treated with DC shock (peak A wave, 60 +/- 9 vs 31 +/- 8 msec, P < 0.001; AEF 11.3 +/- 3 vs 5 +/- 2.9 dynes, P < 0.001). In both groups, AEF increases over time. In conclusion, AEF is a noninvasive parameter that can be easily measured after cardioversion and can give accurate information about the recovery of left atrial mechanical function. This finding may have important implications for guiding the anticoagulant therapy after cardioversion. PMID- 9990599 TI - Steroid eluting high impedance pacing leads decrease short and long-term current drain: results from a multicenter clinical trial. CapSure Z investigators. AB - Pacemaker lead technology has changed considerably over the past decades. The widespread use of low polarization highly porous electrodes and steroid elution electrodes has resulted in low chronic pacing thresholds, as well as a decrease in the incidence of exit block. Efforts to develop pacing leads with high impedance might theoretically lead to lower lead current drain, which is a component of battery capacity. Pulse generator longevity can be increased without sacrificing pacemaker capabilities if pacing current drain can be decreased. Decreasing the size of the stimulation electrode results in increased pacing impedance, and if pacing thresholds are unchanged, a decreased current drain is predicted by Ohm's law (I = V/R). There is limited data available on the pacing characteristics of large numbers of patients with high impedance leads, despite their recent general availability and increasing widespread use. This multicenter, controlled trial examined the differences in performance between standard steroid-eluting pacing leads in the atrium (Medtronic model 5524) and ventricle (Medtronic model 5024), and new high impedance steroid-eluting pacing leads in the atrium (Medtronic model 5534) and ventricle (Medtronic model 5034). Measurements of bipolar pacing thresholds at 2.5 V, pacing impedance, and sensing thresholds were determined within 24 hours of pacemaker implantation, and at 0.5, 1, 3, 6 and 12 months after pacemaker implantation in 609 patients. Pacing and sensing thresholds were similar for the control and high impedance leads at all times except for a slightly larger R wave with the high impedance leads at implantation and 12 months. The mean impedance of the high impedance pacing leads in the atrium and ventricle at 12 months was 992 +/- 175 and 1,080 +/- 220 omega, compared to 522 +/- 69 and 600 +/- 89 omega for the standard pacing leads in the atrium and ventricle (P < or = 0.001 for the high impedance leads compared to standard leads in each chamber). The mean atrial lead current (measured at 2.5 V) at 12 months was 2.6 +/- 0.5 mA with the high impedance lead, and 4.9 +/- 0.7 mA with the standard lead in the atrium (P < or = 0.001). In the ventricle, the mean lead current at 12 months was 2.4 +/- 0.4 mA with the high impedance pacing lead and 4.3 +/- 0.6 mA with the standard lead (P < or = 0.001). High impedance leads are associated with lower lead current drain than standard pacing leads in the atrium and ventricle for up to 1 year. No clinically important differences in sensing characteristics was noted with the high impedance leads in the atrium or ventricle compared to standard pacing leads. High impedance leads may result in increased pulse generator longevity. PMID- 9990600 TI - The dynamic behavior of the diastolic slope of monophasic action potential can be related to the occurrence and maintenance of delayed afterdepolarization dependent arrhythmias. AB - We have described the value of the diastolic slope of the MAP recording at the end of a pacing train as a qualifying marker for the induction of delayed afterdepolarization (DAD) dependent arrhythmias. In the present study (1) the behavior of the slope at different time points during a pacing train was quantified and related to the arrhythmogenic outcome (group A) and (2) termination of DAD dependent VT was related to changes in the slope steepness (group B). In dogs with chronic complete AV block, a MAP was recorded during (1) ventricular pacing, before and after ouabain administration (group A) and (2) 6 spontaneous and 6 lidocaine induced VT terminations (group B). During control (group A), the slope at the end of pacing train was 5 +/- 3 m V/s (mean +/- SD), independent of the pacing duration. During ouabain, this increased to 20 +/- 15 mV/s (P < 0.05), varying with the duration of pacing. The slope was steeper after pacing for 4 seconds, compared to 20 seconds (26 +/- 12 mV/s vs 16 +/- 13 mV/s, P < 0.05) which corresponded with more frequent VT induction. In spontaneously terminating VTs (group B), CL increased from 353 +/- 54 ms at the start to 434 +/ 78 ms (P < 0.05) before VT termination. This corresponded with a decreasing steepness of the slope from 19 +/- 10 mV/s to 6 +/- 5 mV/s (P < 0.05). In lidocaine induced VT termination, the CL and the steepness of the slope showed an identical behavior. There is a dynamic variation in the steepness of the diastolic slope during pacing, which depends on the duration of pacing and predicts arrhythmogenic outcome. Furthermore, a decrease in steepness of the slope during DAD dependent VT can be used to predict VT termination. PMID- 9990601 TI - Reversing the initial phase polarity in biphasic shocks: is the polarity benefit reproducible? AB - The effect of initial phase polarity (IPP) reversal using biphasic shocks on DFT at the time of implantation of implantable cardioverter defibrillator and the reproducibility of this effect during predischarge testing was evaluated in a randomized fashion. Twenty-two patients with ventricular tachycardia or ventricular fibrillation (VF) who received either the Medtronic 7219D (7 patients), 7219C (12 patients), 7223 (1 patient), or CPI Ventak MINI (2 patients) were studied. The DFT was determined in a randomized fashion at implantation and during predischarge testing using a binary search protocol. Initial shock was delivered at 12 J. If successful, subsequent shock was delivered at 6 J, following which the shock was incremented or decremented by 3 J depending upon the success. The DFT for right ventricular (RV)- and RV + IPP was 10.9 +/- 4.1 J and 11.1 +/- 4.0 J, respectively, at implant (P = ns) and 9.7 +/- 4.3 J and 8.4 +/- 6 J, respectively, (P = ns) at predischarge testing. Of the six patients who had better DFT with RV + at implantation, only one patient maintained the benefit during predischarge testing. The differences observed in IPP in individual patients may not be demonstrable during repeated testing. These findings may have implications on how these devices should be programmed. PMID- 9990602 TI - Rate and time dependent effects of D-sotalol on the monophasic action potential after sudden increase of the heart rate. AB - Experimental and clinical data suggests that almost all Class III antiarrhythmic agents diminish their ability to prolong cardiac repolarization at fast heart rates. However, only limited data exists about the time course of efficacy decay of Class III agents after sudden increase of the heart rate. In the present study, we assessed both rate and time dependent changes of the efficacy of d sotalol in higher stimulation frequencies following an abrupt increase in heart rate. This might imitate the situation seen in the development of paroxysmal tachycardias. Monophasic action potentials were recorded from the right ventricular apex during sinus rhythm and constant stimulation with the paced cycle length (PCL) of 550 ms, 400 ms, and 330 ms in the baseline and 20 minutes after intravenous administration of d-sotalol (2.5 mg/kg) in seven patients with documented life-threatening ventricular tachyarrhythmias. D-sotalol significantly prolonged monophasic action potential duration at different steady-state heart rates (sinus rhythm: 21.1% +/- 3.6%; PCL 550 ms: 16.6% +/- 4.3%, 400 ms: 11.2% +/ 2.7%, 330 ms: 5.8% +/- 2.1%). The prolongation is significantly shorter in higher steady-state pacing, confirming a pronounced reverse-use dependent decrease of the efficacy of d-sotalol at faster stimulation frequencies. After the abrupt increase in heart rate, the beat-to-beat adaptation of the postdrug action potential prolongation exhibits only slight reverse-use dependent shortening. The decrease of the efficacy of d-sotalol is insignificant for the first 20 consecutive beats at the stimulation frequency of the PCL of 400 msec (from 16.6% at PCL of 550 ms to 14.6% at the 20th beat of the PCL of 400 ms), and for the first ten consecutive beats at the stimulation frequency of the PCL of 330 ms (from 16.8% at PCL of 550 ms to 12.3% at the 10th beat of the PCL of 330 ms). This slow decay of action potential prolongation after an abrupt increase in heart rate might contribute to the antiarrhythmic action of d-sotalol in cardiac tachyarrhythmias. PMID- 9990603 TI - Automatic capture verification by charge-neutral sensing. AB - Automatic capture verification can prolong pulse generator longevity and increase patient safety. However, the detection of evoked response following pacing is complicated due to afterpotentials caused by polarization of electrodes. This study describes a new capture verification scheme, which neutralizes the charges between the pacing electrodes. The hypothesis of the charge-neutral sensing is that the afterpotentials in the ring and the tip are opposite in polarity when pacing in a bipolar mode between ring and tip. Summing the unipolar signals sensed at the tip and the ring should effectively cancel the afterpotentials. This scheme was implemented in an external computer based system and tested during pacemaker implant/replacement on 23 patients during VVI pacing (17 acutely implanted leads and 6 chronic leads). Surface ECG was recorded to provide a marker for capture and noncapture. The pacing voltage was gradually decreased until a noncapture beat was noted. To avoid fusion beats, the pacing rate was programmed approximately 50% higher than the intrinsic rate. The evoked response was high pass filtered and the integral average was calculated for both capture and noncapture beats. The system signal to noise ratio (SNR) was expressed as ratio of the minimum integral average of all capture beats to the maximum integral average of all noncapture beats. The system SNR was 8.6 +/- 1.3 (mean +/ S.E.M; range 1.5-22.8), indicating that the charge-neutral sensing method has, on average, a ninefold safety margin in providing capture verification. Further, evaluation is needed to fully assess this feature in patients with chronic leads. PMID- 9990604 TI - The potential usage of dual chamber pacing in patients with implantable cardioverter defibrillators. AB - Bradycardia support by ICDs has been limited to fixed rate, ventricular pacing. Concomitant placement of a pacemaker and an ICD exposes a patient to potentially life-threatening device interactions. ICDs capable of dual chamber pacing have recently become available. The number of ICD recipients who stand to benefit from the addition of dual chamber pacing is debated, but no data have addressed this question. This retrospective study analyzed all patients who received nonthoractomy ICD system placement at the Mayo Clinic in Rochester, MN between March 1991 and October 1996 in order to determine the proportion of patients in whom a dual chamber pacing ICD may be indicated. DEFINITIONS: (1) Definitely indicated = pacemaker present at ICD implant or NASPE Class I pacing indication; (2) Probably indicated = NASPE Class II pacing indication, NYHA Functional Class III or IV, or history of systolic congestive heart failure; (3) Possibly indicated = history of paroxysmal atrial fibrillation or an ejection fraction < or = 20%. The results were that nonthoracotomy ICDs were placed in 253 patients. A dual chamber ICD would have been definitely indicated in 11% of the study group, probably indicated in 28%, and possibly indicated in 14%. Chronic atrial fibrillation was present at ICD implant in 6.7% of patients and developed in 0.9%/yr during follow-up. The addition of dual chamber pacing to ICDs stands to potentially benefit approximately half (53%) of ICD recipients. These data do not address all patients who may benefit from dual chamber sensing. PMID- 9990605 TI - Controlled ventilation enhances catheter stability during radiofrequency ablation. AB - Variations in the amplitude of the atrial and ventricular depolarization waves of the intracardiac electrogram occur during different phases of respiration. Therefore, we tested whether controlled ventilation would reduce ablation attempts and increase the rate of success in patients undergoing radiofrequency ablation with general anesthesia. Thirty-eight children were divided into two groups: (1) controlled and (2) noncontrolled or cyclic ventilation. In the controlled ventilation group, the mapping electrogram was recorded during sustained inspiration, sustained expiration, and cyclic ventilation. Ablation was done in the phase of ventilation that had the least variability in atrial and ventricular amplitudes. Seventeen patients in the controlled ventilation group had tracings adequate for review. In eight patients, ablation was done during sustained inspiration with the percentage change of atrial and ventricular amplitudes (15% +/- 16% and 13% +/- 16%, respectively) being < that during sustained expiration (38% +/- 27%, P = 0.04 and 20% +/- 21%) or during cyclic ventilation (57% +/- 27%, P < 0.01 and 54% +/- 26%, P = 0.003). In nine patients, ablation was done during sustained expiration with the percentage change of atrial and ventricular amplitudes (5% +/- 5% and 5% +/- 2%) being less than that during sustained inspiration (21% +/- 14%, P = 0.01 and 11% +/- 6%, P = 0.01) or during cyclic ventilation (68% +/- 23%, P < 0.001 and 48 +/- 26%, P = 0.001). We achieved success with each patient in both groups, but the number of ablation attempts were less in the controlled ventilation group 1 (3 +/- 2), as compared to the cyclic ventilation group 2 (8 +/- 8; P < 0.02). We concluded that controlled ventilation reduced the number of ablation attempts and facilitated the ablation procedure. PMID- 9990606 TI - The long QT syndrome and torsade de pointes. AB - The LQTS is a prime example of how molecular biology, ion channel, cellular, and organ physiology, coupled with clinical observations, promise to be the future paradigm for advancement of medical knowledge. Both the congenital and acquired LQTS are due to abnormalities (intrinsic and/or acquired) of the ionic currents underlying cardiac repolarization. In this review, the continually unraveling molecular biology of congenital LQTS is discussed. The various pharmacological agents associated with the acquired LQTS are listed. Although it is difficult to predict which patients are at risk for TdP, careful assessment of the risk benefit ratio is important before prescribing drugs known to be able to cause QT prolongation. The in vivo electrophysiological mechanism of TdP in the LQTS is described using, as a paradigm, the anthopleurin-A canine model, a surrogate for LQT3. In the LQTS, prolonged repolarization is associated with increased spatial dispersion of repolarization. Prolongation of repolarization also acts as a primary step for the generation of EADs. The focal EAD induced triggered beat(s) can infringe on the underlying substrate of inhomogeneous repolarization to initiate polymorphic reentrant VT, sometimes having the characteristic twisting QRS configuration known as TdP. The review concludes by discussion of the clinical manifestations and current management of both the congenital and acquired LQTS. The initial therapy of choice for the large majority of patients with the congenital LQTS is a beta-blocking drug. This therapy seems to be effective in LQT1 and LQT2 patients, but may not be as effective in LQT3 patients. Other therapeutic options include pacemakers, cervicothoracic sympathectomy, and the implantable cardioverter defibrillator. Recent molecular genetic studies have suggested several genotype specific therapies; however, long term efficacy data are not available. PMID- 9990607 TI - Spontaneous termination of ventricular tachycardia with variable patterns and variable mechanisms? AB - A 43-year-old man, with repeated episodes of postmyocardial infarction monomorphic VT, had three forms of induced sustained VT in the electrophysiology lab. The three forms of VT had variable termination patterns with no change, decrease, or increase of cycle length. PMID- 9990608 TI - Estimating practice expense: are we forever lost in an accounting labyrinth? PMID- 9990609 TI - Management of pacing system related complications in patients undergoing dynamic cardiomyoplasty. AB - Integrity of the electrical circuit is a necessary requirement for appropriate heart/wrapped skeletal muscle interaction to be achieved in cardiomyoplasty. This article describes the management of two different complications after a cardiomyoplasty procedure involving the electrical system (infection of the abdominal cardiomyostimulator pocket and intramuscular lead fracture). Minimal approaches were carried out, which ensured the successful treatment of the infective and of the mechanical insult, and represent useful strategy for solving such uncommon problems. PMID- 9990610 TI - A nodoventricular fiber associated with dual AV nodal conduction, AV nodal reentrant tachycardia, and anterior location of the slow AV nodal pathway. AB - We present a case of a patient with a nodoventricular tract, associated with dual AV nodal conduction and AV nodal reentrant tachycardia, and an anteroseptal location of the slow AV nodal pathway. The remarkable feature of this case is the site of successful ablation, in the anteroseptum just anterior and superior to the His bundle, where both preexcitation and dual AV nodal physiology were abolished. PMID- 9990611 TI - Irregular ventricular stimulation in the DDI mode of a dual chamber pacemaker with atrial-based lower rate timing. AB - This report describes two patients with atrial fibrillation in whom an implanted CHORUS DDD pacemaker programmed to the DDI mode produced an irregular ventricular stimulation rate. The lower rate timing of these devices is atrial-based only when an atrial event opens an AV interval shorter than the programmed AV delay. In the DDI mode, if Api represents the time when an atrial paced event (Ap) would have occurred if it had not been inhibited by a previous atrial sensed event (As), then Api-Vp constitutes the implied AV interval where Vp is a paced ventricular event. Although the As-Vp interval (As-Api + Api-Vp) generates an atrial refractory period during its entire duration, the pacemaker can sense an atrial event (AR) during the implied AV interval. AR cannot start another AV delay, but it can initiate the atrial-based lower rate interval. This timing mechanism can cause irregular prolongation of Vp-Vp intervals to a value longer than the programmed lower interval with a maximal extension equal to the programmed AV delay. Such behavior of the CHORUS pacemaker should not be interpreted as malfunction. PMID- 9990613 TI - Successful radiofrequency ablation of an accessory pathway during pregnancy. AB - The preexcitation syndrome is a rare entity during pregnancy. We present a 20 week pregnant patient with Wolff-Parkinson-White syndrome and recurrent episodes of tachycardia with hemodynamic compromise refractory to medical treatment that required electrical cardioversion several times. Due to the poor evolution we performed a successful radiofrequency ablation of a right posteroseptal accessory pathway using 70 seconds of total fluoroscopy time without complications. We consider this is an alternative and safer treatment in those cases in which the tachyarrhythmias compromise the hemodynamic state during pregnancy. PMID- 9990612 TI - Radiofrequency catheter ablation of ventricular tachycardia guided by nonsurgical epicardial mapping in chronic Chagasic heart disease. AB - We report a case of a 63-year-old women with Chagas' disease and recurrent, syncopal VT treated by RF catheter ablation in whom endocardial application of RF energy was guided by nonsurgical epicardial mapping. The procedure was undertaken in the electrophysiology laboratory under deep anesthesia. VT was interrupted after 2.4 seconds of application and rendered noninducible afterwards. Two weeks after the procedure, a distinct morphology VT was induced by programmed ventricular stimulation, and the patient was started on amiodarone, remaining asymptomatic 12 months after the procedure. PMID- 9990614 TI - Diagnostic value of a pacemaker high rate episode counter when programming the ventricular tachycardia zone of an ICD. AB - A 72-year-old man with an ICD and a pacemaker was presented with an episode of sustained VT that accelerated to VF. The ICD failed to detect the event and deliver therapy, despite a VT apparently within the VT detection zone. The ICD detected the event after degeneration to VF and delivered appropriate therapy. The high rate event feature of the pacemaker was useful in determining proper function of the ICD along with optimal programming of VT detection. PMID- 9990615 TI - Use of an implantable cardioverter defibrillator in an eight-month-old infant with ventricular fibrillation arising from a myocardial fibroma. AB - We report our experience with use of a ICD in a 7-month-old infant who presented with VF. We utilized an epicardial patch and active generator in the abdomen. Development of mediastinitis required explantation and eventual replacement with a subcutaneous patch and active generator in the abdomen. PMID- 9990616 TI - Inadvertent placement of pacemaker or ICD leads in some parts of the coronary venous system. PMID- 9990617 TI - Quality of life and clinical outcomes in elderly patients treated with ventricular pacing as compared with dual-chamber pacing. PMID- 9990618 TI - Autocapture function was introduced to save battery energy and to prolong generator longevity. PMID- 9990619 TI - A case of sotalol associated torsades de pointes tachycardia in a 15 month old child. PMID- 9990620 TI - The influence of specific and nonspecific potassium current blockade on the defibrillation energy requirement of biphasic shock. AB - Block of delayed rectifier potassium current (IK) is known to decrease defibrillation energy requirements (DERs). We tested the hypothesis that there would be no difference in DER reduction with a nonspecific IK (IKr + IKs) blocker, ambasilide, and a specific IKr blocker, dofetilide. METHODS: An anesthetized canine model (n = 30) of internal transvenous defibrillation with biphasic shocks was used. Ambasilide (n = 9; dose: 4.8 mg/kg, then 9.6 mg/kg/hour), dofetilide (n = 10; dose: 10 (micrograms/kg, then 3.6 (micrograms/kg/hour), or matched placebo (n = 11) were administered. DERs (J) were determined in triplicate using an increment-decrement protocol at baseline and during each treatment. ECG intervals were measured at baseline and during each treatment. ANOVA with post-hoc Bonferroni test was used for statistical analysis. RESULTS: Ambasilide resulted in a +23.5 +/- 4.06% prolongation of the QTc interval, while dofetilide resulted in a +20.5% +/- 3.76% prolongation of the QTc interval. Thus, the two drugs resulted in comparable prolongation of the QTc interval (P < 0.05 compared to placebo). Both drugs significantly reduced the DER (-17.7% +/- 5.33% reduction by ambasilide, and -21.9% +/- 5.21% reduction by dofetilide, P < 0.05 compared to placebo). There was no difference in the magnitude of DER reduction between the two treatments. CONCLUSIONS: Administration of equipotent doses (as indicated by QTc changes) of ambasilide or dofetilide had comparable effects on DERs. Selectivity of IK blockade has no significant effect on the magnitude of reduction in DERs. PMID- 9990621 TI - Defibrillation efficacy of different electrode placements in a human thorax model. AB - The objective of this study was to measure the defibrillation threshold (DFT) associated with different electrode placements using a three-dimensional anatomically realistic finite element model of the human thorax. Coil electrodes (Endotak DSP, model 125, Guidant/CPI) were placed in the RV apex along the lateral wall (RV), withdrawn 10 mm away from the RV apex along the lateral wall (RVprox), in the RV apex along the anterior septum (RVseptal), and in the SVC. An active pulse generator (can) was placed in the subcutaneous prepectoral space. Five electrode configurations were studied: RV-->SVC, RVprox-->SVC, RVSEPTAL- >SVC, RV-->Can, and RV-->SVC + Can. DFTs are defined as the energy required to produce a potential gradient of at least 5 V/cm in 95% of the ventricular myocardium. DFTs for RV-->SVC, RVprox-->SVC, RVseptal-->SVC, RV-->Can, and RV- >SVC + Can were 10, 16, 7, 9, and 6 J, respectively. The DFTs measured at each configuration fell within one standard deviation of the mean DFTs reported in clinical studies using the Endotak leads. The relative changes in DFT among electrode configurations also compared favorably. This computer model allows measurements of DFT or other defibrillation parameters with several different electrode configurations saving time and cost of clinical studies. PMID- 9990622 TI - Impact of transvenous lead position on active-can ICD defibrillation: a computer simulation study. AB - Optimizing lead placement in transvenous defibrillation remains central to the clinical aspects of the defibrillation procedure. Studies involving superior vena cava (SVC) return electrodes have found that left ventricular (LV) leads or septal positioning of the right ventricular (RV) lead minimizes the voltage defibrillation threshold (VDFT) in endocardial lead-->SVC defibrillation systems. However, similar studies have not been conducted for active-can configurations. The goal of this study was to determine the optimal lead position to minimize the VDFT for systems incorporating an active can. This study used a high resolution finite element model of a human torso that includes the fiber architecture of the ventricular myocardium to find the role of lead positioning in a transvenous LEAD ->can defibrillation electrode system. It was found that, among single lead systems, posterior positioning of leads in the right ventricle lowers VDFTs appreciably. Furthermore, a septal location of leads resulted in lower VDFTs than free-wall positioning. Increasing the number of leads, and thus the effective lead surface area in the right ventricle also resulted in lower VDFTs. However, the lead configuration that resulted in the lowest VDFTs is a combination of mid cavity right ventricle lead and a mid-cavity left ventricle lead. The addition of a left ventricular lead resulted in a reduction in the size of the low gradient regions and a change of its location from the left ventricular free wall to the septal wall. PMID- 9990623 TI - The effect of shock configuration and delivered energy on defibrillation impedance. AB - Shock impedance is an important determinant of defibrillation efficacy. Lead configuration, shock polarity, and delivered energy can affect shock impedance, but these variables have not been studied in active can lead systems. The present study was a prospective evaluation of 25 patients undergoing initial transvenous defibrillator implantation. In all patients, a dual coil lead and pectoral emulator were placed and three lead configurations were tested in random order: Lead (distal to proximal coil), unipolar (distal coil to can), and triad (distal coil to can + proximal coil). Shock energies of 0.1- to 15-J shock were evaluated. Impedance increased a mean of 21% as delivered energy was decreased (P < 0.001), an effect independent of lead configuration. At all delivered energies, impedances in the unipolar configuration were about 40% higher than triad, while the lead configuration was about 20% higher than triad (ps < 0.001). Polarity did not affect impedance. These results indicate that transvenous lead configurations and delivered energy, but not polarity, significantly influence shock impedance. The magnitude of the increase of impedance at low energies is independent of the shocking pathway. This effect has important implications for low energy shocks used to terminate atrial fibrillation or ventricular tachycardia. PMID- 9990624 TI - Clinical evaluation of a prototype passive fixation dual chamber single pass lead for dual chamber ICD systems. AB - Dual chamber ICD systems use two separate leads for sensing. We developed and tested a new prototype of a single pass dual chamber passive fixation lead for dual chamber ICDs. METHODS AND RESULTS: The prototype was a modification of the Guidant CPI Endotak DSP lead. The additional sensing electrode for the right atrium consisted of a side-mounted porous atrial ring electrode (AR). Atrial signals were recorded from the lead in patients during normal sinus rhythm (NSR), atrial fibrillation (AFib), and/or atrial flutter (AFl) with the AR in stable contact with the atrial wall or floating. During NSR, with the AR in contact with the atrial wall, an average P wave amplitude of 7.2 +/- 1.5 mV (mean +/- SD, n = 12) was measured. After induction of Afib/AFl, the single amplitude decreased to 3.6 +/- 1.5 mV (n = 8) during AFib and 3.4 +/- 1.7 mV (n = 9) during AFl. Amplitudes dropped between 53% and 75% when the AR lost atrial wall contact. The atrial pacing threshold was 1.0 +/- 0.4 V (n = 16) when the AR was in contact with the atrial wall. CONCLUSIONS: In future dual chamber ICDs the signals from a passive fixation single pass lead could be used for atrial sensing and pacing as long as the sensing electrode for the right atrium remains in contact with the atrial wall. This system might lead to a simpler, less invasive implantation of dual chamber ICD systems. PMID- 9990625 TI - Reliability of coated wire defibrillation leads. AB - A higher rate of complications and need for reoperation has been identified with epicardial and endocardial defibrillator systems. Improved reliability may be achieved with alternate designs that use coated wire and coated coil conductors. Six-year reliability in the 98% range is reported for one bipolar design, the Sulzer Intermedics Intervene lead. PMID- 9990626 TI - A new defibrillator discrimination algorithm utilizing electrogram morphology analysis. AB - Inappropriate therapies delivered by implantable cardioverter defibrillators (ICDs) for supraventricular arrhythmias remain a common problem, particularly in the event of rapidly conducted atrial fibrillation or marked sinus tachycardia. The ability to differentiate between ventricular tachycardia and supraventricular arrhythmias is the major goal of discrimination algorithms. Therefore, we developed a new algorithm, SimDis, utilizing morphological features of the shocking electrograms. This algorithm was developed from electrogram data obtained from 36 patients undergoing ICD implantation. An independent test set was evaluated in 25 patients. Recordings were made in sinus rhythm, sinus tachycardia, and following the induction of ventricular tachycardia and atrial fibrillation. The arrhythmia complex is defined as wide if the duration is at least 30% greater than the template in sinus rhythm. For narrow complexes, four maximum and minimum values were measured to form a 4-element feature vector, which was compared with a representative feature vector during normal sinus rhythm. For each rhythm, any wide complex was classified as ventricular tachycardia. For narrow complexes, the second step of the algorithm compared the electrogram with the template, computing similarity and dissimilarity values. These values were then mapped to determine if they fell within a previously established discrimination boundary. On the independent test set, the SimDis algorithm correctly classified 100% of ventricular tachycardias (27/27), 98% of sinus tachycardias (54/55), and 100% of episodes of atrial fibrillation (37/37). We conclude that the SimDis algorithm yields high sensitivity (100%) and specificity (99%) for arrhythmia discrimination, using the computational capabilities of an ICD system. PMID- 9990627 TI - A fuzzy logic-controlled classifier for use in implantable cardioverter defibrillators. AB - PURPOSE: Implantable cardioverters defibrillators (ICDs) are increasingly used in the management of life-threatening arrhythmias. Correct recognition of a treatable arrhythmia is crucial to this application. However, the computational power of microprocessors currently used in ICDs limits the range of traditional algorithms available for this application. METHODS: Classification based on fuzzy inference systems (FIS) were trained to recognize different cardiac rhythms (AF, VF, SVT, VT) from the Ann Arbor Electrogram Library. The FIS used were designed using adaptive-network-based fuzzy inference methods to optimize the classification procedure. Only computational techniques suitable for ICD design were used. RESULTS: After pretraining with the ANFIS correct rhythm classification was observed for the rhythms studied. CONCLUSION: In this preliminary study, successful rhythm classification was demonstrated using fuzzy logic techniques. In view of the computational efficiency this may have application in ICD design. PMID- 9990628 TI - Clinical significance of consecutive shocks in patients with left ventricular dysfunction treated with implantable cardioverter defibrillators. AB - The purpose of the present study was to determine the clinical significance of consecutive automatic shocks delivered by implantable cardioverter defibrillators (ICDs). Sixty-four patients who received ICDs at our institution between January 1990 and July 1997 were included in this study. There were 53 men and 11 women with a mean age of 50 +/- 14 years. During a follow-up period ranging between 0.2 and 73 months (mean 23 +/- 21 months), 17 patients received consecutive shocks (group A), 29 patients received single shocks (group B), and 18 patients received no ICD therapy (group C). Clinical characteristics, episodes of ICD therapy, and prognosis were compared among the three groups. There were no significant differences among the three groups with regard to clinical characteristics, time to first ICD therapy, number of antitachycardia pacing episodes, or frequency of inappropriate discharges. The mortality rate was higher in group A than in groups B and C (P = 0.0021). The sensitivity of consecutive shocks in predicting death was 70%, the specificity was 88%, and the predictive accuracy was 81% in patients with left ventricular ejection fractions < 35%. In summary, consecutive shocks are a clinically important event in patients with ICDs. Specifically, patients who receive consecutive shocks and have a depressed left ventricular function should be considered particularly high risk. PMID- 9990629 TI - Prehospital discharge defibrillation testing in ICD recipients: a prospective study based on cost analysis. AB - Prehospital discharge defibrillation testing is often performed to verify the function of newly implanted cardioverter defibrillators (ICDs). To determine whether elimination of predischarge testing could reduce costs without placing patients at additional risk, 31 patients were randomized in this prospective clinical evaluation to either receive or not receive a predischarge ICD defibrillation test. Expenses associated with postimplant care was the primary endpoint. All patients underwent induction of ventricular fibrillation after 6 months to evaluate ICD function. The groups were well matched in terms of patient characteristics, initial lead implant parameters, and defibrillation thresholds. Elimination of prehospital discharge testing resulted in a savings of $1,800/patient after 6 months, with no difference between groups in terms of ICD complication rates or unanticipated hospital admissions. Further studies are needed to better define the most appropriate time to assess defibrillation thresholds in the first year after implantation. PMID- 9990630 TI - Late retesting of system performance in ICD patients without spontaneous shocks. AB - One hundred five implantable cardioverter defibrillator (ICD) patients (71 +/- 9 years of age, 83% men) without spontaneous ICD discharges for > or = 12 months were tested to assess high voltage (HV) circuit integrity and the system's ability to recognize and terminate ventricular fibrillation (VF). Indications for ICD implantation were sustained ventricular tachycardia (VT) (35%), cardiac arrest (27%), and inducible VT (38%). Eighty-two percent of the patients had coronary artery disease (CAD), and the mean left ventricular ejection fraction (LVEF) was 36% +/- 13%. RESULTS: One hundred patients had inducible VF and five did not. Testing led to ICD reprogramming in 50 (49%) patients. Two (1.9%) patients required ICD replacement: (1) a 45-year-old patient with a Ventritex 110 ICD implanted for 13 months interfaced with a CPI 0062 lead implanted for 46 months could not be defibrillated internally (impedance nonmeasurable); (2) an 82 year-old patient with a 23-month-old Medtronic 7219 ICD interfaced with 6936 and 6933 leads whose defibrillation threshold (DFT) had doubled since implantation (24 J from 12 J). Lead fractures were found in both cases (proximal coil of the 0062, and subcutaneously in the 6933). Based on DFT determinations, the first shock output was programmed lower in 37 patients and higher in 10 patients. Shock pulse width was changed in one patient and the ventricular refractory period in another. No programming changes were made in 54 (51%) patients. CONCLUSIONS: (1) Late testing of HV circuit integrity in ICD patients without an ICD shock in > or = 12 months identifies previously unsuspected HV lead fractures; (2) chronic DFT testing resulted in HV output reprogramming in one-half of the patients. PMID- 9990631 TI - Time to first shock in implantable cardioverter defibrillator (ICD) patients with Chagas cardiomyopathy. AB - The time to first ICD shock has been extensively studied in patients with coronary artery disease (CAD). However, there are no published data on ICD shocks in patients with Chagas cardiomyopathy (ChC). The occurrence of the first appropriate ICD shock during the first 6 months of follow-up in 20 patients with ChC (group 1) and 35 CAD patients (group 2) was analyzed retrospectively. All patients had received a third-generation pectoral ICD for ventricular tachycardia or fibrillation (VT/VF). Indications for ICD implantation were refractoriness to drug therapy or noninducibility of VT/VF at EPS in cardiac arrest survivors. RESULTS: The mean age, left ventricular ejection fraction (LVEF), and sex in groups I and II were 57.4 +/- 7 years versus 64 +/- 9 (P < 0.01), 30.9% +/- 10% versus 32.9% +/- 10% (P = NS), and 10 men versus 31 women (P < 0.005), respectively. Six months after ICD implantation, 85% (17/20) group I patients received appropriate ICD shocks versus 51% (18/35) in group 2, a statistically significant difference (P < 0.02, RR: 1.65, OR: 5.35). CONCLUSIONS: The incidence of appropriate ICD shocks within the first 6 months postimplantation was significantly higher in ChC patients than in CAD patients. ChC patients were younger and more often women than CAD patients. PMID- 9990633 TI - Patient discomfort following pectoral defibrillator implantation using conscious sedation. AB - BACKGROUND: The miniaturization of implantable cardioverter defibrillators (ICDs) has made pectoral implantation possible. However, postoperative pain following the procedure has not been systematically studied. The aim of the current study was to prospectively assess patient discomfort and identify factors influencing pain perception during follow-up. METHODS: Pain related to device implantation was quantified in 21 consecutive patients (age, 61 +/- 11 years; 17 men and 21 women; 16 of 21 had coronary artery disease; left ventricular ejection fraction, 32% +/- 15%) undergoing pectoral ICD implantation with conscious sedation (fentanyl 118 +/- 72 micrograms midazolam 14 +/- 9 mg). Patients completed the Visual Analogue Scale (VAS, 0-100) and the McGill Pain Questionnaire 24 hours and 1 month postoperatively. Regression analysis was used to define clinical and procedure related variables affecting patient discomfort and frequency of postoperative analgesic use. RESULTS: The mean VAS score was 34 +/- 20 24 hours postoperatively. A single (4.8%) patient described postoperative pain as severe. Pain was reported to be moderate by 10 (47.6%) patients and mild by 10 (47.6%) patients. Intraoperative fentanyl requirement was a predictor of postoperative pain (R = 0.51, P = 0.036), and procedural duration was a strong predictor of postoperative analgesic use (R = 0.75, P < 0.001). Pain at 1 month decreased to a VAS score of 19 +/- 18 (P = 0.002 vs 24 hours) and was rated to be severe, moderate, and mild by 1, 3, and 17 patients, respectively. Late pain was related to a VAS score at 24 hours (R = 0.67, P = 0.004). CONCLUSIONS: (1) Pectoral ICD implantation using conscious sedation is well tolerated. (2) Postoperative discomfort correlates with longer procedural times and larger intraoperative narcotic requirements. PMID- 9990632 TI - Complications of third-generation implantable cardioverter defibrillator therapy. AB - To determine the incidence of complications of third-generation implantable cardioverter defibrillator (ICD) therapy, 144 patients were prospectively studied who underwent first implant of third-generation devices (i.e., ICD systems with biphasic shocks, ECG storage capability, and nonthoracotomy lead systems). During 21 +/- 15 months of follow-up, 41 (28%) patients had one or more complications. No patient died perioperatively (30 days) and no ICD infection was observed during follow-up. Complications included bleeding or pocket hematoma (hemoglobin drop > 2 g/dL) in 5 (3%) patients, prolonged reversible ischemic neurological deficit in 1 (1%) patient, postoperative deep venous thrombosis of leg in 1 (1%) patient, pneumothorax in 2 (1%) patients, difficulty to defibrillate ventricular fibrillation intraoperatively in 2 (1%) patients, generator malfunction in 1 (1%) patient, arthritis of the shoulder in 3 (2%) patients, and allergic reaction to prophylactic antibiotics in 2 (1%) patients. A total of seven lead related complications were observed in six (4%) patients including endocardial lead migration in four (3%) patients. Twenty-three (16%) patients received inappropriate shocks for supraventricular tachyarrhythmias (n = 13), non sustained ventricular tachycardia (VT) (n = 7), or myopotential oversensing (n = 3). We conclude that serious complications such as perioperative death or ICD infection are rare in patients with third-generation ICDs. Lead-related problems and inappropriate shocks during follow-up are the most frequent complications of third-generation ICD therapy. Recognition of these complications should promote advances in ICD technology and management strategies to avoid their recurrence. PMID- 9990634 TI - Syncope is predicted by neuromonitoring in patients with ICDs. AB - Decisions regarding ability of ICD patients to function in the work environment or at home are based primarily on subjective judgement. We have described noninvasive neuromonitoring techniques that are capable of characterizing cerebral blood flow and cerebral oxygen saturation in conscious patients during ventricular tachycardia (VT). Upright tilt testing (HUT) was used to predict the hemodynamic response to VT in the upright and recumbent posture. Sixteen patients (66 +/- 8 years) with pace-terminable VT and implanted ICD were tested during HUT with continuous measurement of arterial pressure, transcranial Doppler of the middle cerebral artery (TCD), and cerebral venous oxygen saturation (CVOS) determined noninvasively by applying a cutaneous patch with two infrared sensors from which a weighted venous percent oxygenated hemoglobin is continuously measured using INVOS 3100 (Somanetics). VT was induced via the implanted ICD and automatically terminated by ATP or cardioversion by the ICD, using the best treatment algorithm. HUT accentuated changes in cerebral blood flow and oxygen saturation and helped identify patients likely to experience syncope, whereas supine testing did not. These results suggest that HUT testing with noninvasive neuromonitoring is useful to predict ICD patients who are likely to remain conscious during VT. PMID- 9990635 TI - Clinical significance of sleep-related breathing disorders in patients with implantable cardioverter defibrillators. AB - The prevalence and clinical significance of sleep-related breathing disorders (SRBDs) in patients with cardiac disease and a history of life-threatening ventricular tachyarrhythmias is unclear. Forty consecutive recipients of implantable cardioverter defibrillators (ICDs) with cardiac disease and a documented history of spontaneous, life-threatening, ventricular tachyarrhythmias underwent full night polysomnography. SRBDs were diagnosed if the apnea/hypopnea index was > 10. SRBD were diagnosed in 16 of 40 patients (40%): central sleep apnea (CSA) was present in 9 of these 16 patients (56%), 8 of whom had associated Cheyne-Stoke respiration. Seven of the 16 patients with SRBD (44%) had obstructive sleep apnea (OSA). Patients with and without SRBDs were comparable with respect to left ventricular ejection fraction, NYHA classification, underlying heart disease, ICD indications, and concomitant antiarrhythmic drug and beta-blocker therapy. Patients were followed prospectively for 2 years. ICD treated ventricular tachyarrhythmias occurred in 10 of 24 patients (42%) without SRBD, in 4 of 9 patients (44%) with CSA, and in 3 of 7 patients (44%) with OSA (NS). The numbers and circadian distributions of episodes recorded during follow up in patients without SRBD versus with CSA or OSA were not significantly different (14 +/- 25, median = 4 vs 4 +/- 5, median = 2.5 vs 15 +/- 15, median = 7, respectively). The 2-year mortality, which was entirely attributable to nonsudden cardiac events, was highest in patients with CSA (4/9 [44%], vs 0/7 [0%] with OSA, vs 3/24 patients (12.5%) without SRBD; P < 0.05). PMID- 9990636 TI - Initial experience with a new balloon-guided single lead catheter for internal cardioversion of atrial fibrillation and dual chamber pacing. AB - BACKGROUND: Based on the observation that internal cardioversion (IntCV) of atrial fibrillation is effective with electrodes in the right atrium and pulmonary artery, a new balloon-guided catheter and external defibrillation device with optional dual chamber pacing was evaluated. METHODS: IntCV was attempted in 27 patients (age: 57 +/- 10 years, duration: 14 +/- 18 months, left atrial diameter 56 +/- 8 mm) using a new defibrillation device (Alert, EP MedSystems, Inc., NJ, USA) that allows the delivery of biphasic shocks (0.5-15 J, variable tilt), atrial and ventricular pacing, and online signal recording. Pacing and defibrillation shocks were applied via a 7.5 Fr balloon-guided catheter (EP MedSystems, Inc.). Pacing, sensing, and triggering were established through the proximal atrial array and an electrode ring between both defibrillation arrays and a single ventricular electrode ring. Catheters were inserted from the antecubital vein. RESULTS: In 25 of 27 patients sinus rhythm was restored with a mean energy of 6.7 +/- 4.5 J. In five patients, atrial postshock pacing was required for bradycardia and atrial premature beats. The mean fluoroscopy time was 2.0 +/- 1.3 minutes. CONCLUSION: The high success rate, ease of application, and backup dual chamber pacing suggest that this system is an alternative to established methods of cardioversion. In certain indications, such as failure of prior external cardioversion and situations in which a standard pulmonary balloon catheter is needed, this system would be advantageous. PMID- 9990637 TI - Improved clinical efficacy of external cardioversion by fluoroscopic electrode positioning and comparison to internal cardioversion in patients with atrial fibrillation. AB - BACKGROUND: Despite using different electrode positions, "conventional" external DC cardioversion in patients with atrial fibrillation is ineffective in 6%-50% of cases. An alternative when DC cardioversion is not successful is low energy internal cardioversion, which is performed at increased risk. We tested the hypothesis that optimization of electrode pad position under fluoroscopy to encompass as much atrial muscle as possible might improve the success rate of external cardioversion and thus minimize the need for internal cardioversion. METHODS: Fifteen (9 males, 6 females) patients (age: 54 +/- 15 years, weight: 124 +/- 35 kg) with chronic atrial fibrillation (> 8 weeks) who had undergone unsuccessful conventional external cardioversion entered the study. Repeat conventional external cardioversion with electrodes in standard (right anterior and left posterior) positions was followed by "optimized" external cardioversion by positioning electrodes under fluoroscopy (using metallic markers). In case of failure, internal cardioversion was performed. RESULTS: All 15 patients had undergone unsuccessful conventional external cardioversion with 360-J shocks. Eight patients (group A) reverted to sinus rhythm with one or two 360-J shocks using fluoroscopy-guided pad placement (53%). Six of the remaining 7 (86%) patients (group B) had successful internal cardioversion with biphasic shocks (12 +/- 3 J). The body weight and body mass index were statistically lower in group A vs group B (106 +/- 27 vs 145 +/- 33 kg, p = 0.03 and 35 +/- 8 vs 45 +/- 8 kg/m2, P = 0.48, respectively). There was no statistically significant in age, height, body surface area, duration of atrial fibrillation, amiodarone therapy, ejection fraction, or underlying heart disease. CONCLUSION: Unsuccessful external DC cardioversion, in some patients, is in part due to suboptimal conventional positioning of electrode pads that can be improved under fluoroscopic guidance by achieving the best possible vector encompassing the right and left atria. The optimized external cardioversion technique may minimize the need for internal cardioversion, which remains an effective approach when external cardioversion fails. PMID- 9990639 TI - Low energy internal atrial cardioversion in atrial fibrillation lasting more than a year. AB - The aim of this study was to evaluate the efficacy of low energy internal atrial cardioversion in restoring sinus rhythm (SR) in patients with chronic atrial fibrillation (AF) persisting > 1 year. Fifteen patients with chronic AF lasting > 1 year (from 13-48 months, mean 24 +/- 13 months) were studied. R wave synchronized 3/3 ms biphasic shocks were delivered between right atrial and coronary sinus (left pulmonary artery in five patients) electrodes. Sedatives or anesthetics were administered only at the patient's request. RESULTS: Stable SR was restored in 14 (93%) of 15 patients after shocks with a mean leading edge voltage of 377 +/- 77 V (range 260-500) and a mean delivered energy of 7.3 +/- 3.4 J (range 2.6-12.9). The procedure was performed without anesthesia in 6 (40%) patients. All successfully cardioverted patients were treated with flecainide, sotalol, or amiodarone. During a follow up of 7.7 +/- 7.9 months (range 1-24) AF recurred in five (36%) patients. Three of five AF recurrences occurred within 3 days after conversion to SR. CONCLUSION: Internal low energy atrial cardioversion is highly effective in restoring SR even in patients with AF lasting > 1 year. The long-term results from the standpoint of freedom from AF recurrences, are satisfactory, although additional antiarrhythmic treatment is required, particularly in the first days after conversion. PMID- 9990638 TI - Effect of increased parasympathetic and sympathetic tone on internal atrial defibrillation thresholds in humans. AB - Although changes in autonomic tone affect ventricular defibrillation, little is known about the effect of increased parasympathetic or sympathetic tone on the atrial defbrillation threshold. METHODS: To evaluate the effect of reflexly increased parasympathetic and increase alpha- and beta-adrenergic tone on the atrial defibrillation threshold (ADFT), atrial fibrillation was induced in 14 patients. ADFTs, right atrial refractory period (RARP), and monophasic action potential duration (MAPD) were determined before and after autonomic intervention. ADFTs were determined with a step-up protocol using 3/3-ms biphasic shocks delivered through decapolar catheters in the right atrial appendage and coronary sinus. Two groups were studied. Group I (N = 8) had ADFTs determined at baseline, after receiving phenylephrine (PE), and with PE plus atropine (A). Group 2 (N = 6) had ADFTs determined at baseline and after receiving isoproterenol (ISO). RESULTS: Group I: PE significantly increased sinus cycle length (SR-CL) compared to baseline (742 +/- 123 to 922 +/- 233 ms) without significantly changing RARP, MAPD, or ADFT (2.3 +/- 1.3 J vs 2.3 +/- 0.8 J). With PE + A, SR-CL significantly decreased (529 +/- 100 ms vs 742 +/- 123 ms) and MAPD shortened (231 +/- 41 ms vs 279 +/- 49 ms) without altering RARP or ADFT (1.94 +/ 0.9 J vs 2.25 +/- 1.25 J). Group 2: ISO decreased SR-CL (486 +/- 77 ms vs 755 +/ 184 ms) and MAPD (169 +/- 37 ms vs 226 + 58 ms) but not RARP or ADFT (2.25 +/- 1.21 J vs 2.33 +/- 1.75 J). CONCLUSIONS: Increasing parasympathetic, alpha-, or beta-adrenergic tone does not affect the ADFT despite causing significant electrophysiological changes in the atria. PMID- 9990640 TI - Detection of atrial fibrillation during sinus tachycardia induced by exercise in patients with implantable atrial defibrillators. AB - Accurate detection of atrial fibrillation (AF) is essential for appropriate operation of an implantable atrial defibrillator (IAD). However, during episodes of sinus tachycardia, distinction between AF and sinus rhythm (SR) using the "quiet interval" and "baseline crossing" analysis in the detection algorithm of the IAD may be difficult. The efficacy of this AF detection algorithm was tested in five patients implanted with an IAD (METRIX, Model 3000 or 3020, InControl Inc.) during treadmill exercise testing. The IADs were programmed to Monitor Mode with a wake up cycle of 1 minute for AF detection using the device nominal parameters or modified parameters, and to mark rhythms appropriate for shock delivery. A mean peak heart rate of 137 +/- 26 beats/min was reached during maximum exercise, and one patient developed transient AF. Seventy-eight (75 in SR, 3 in AF) and 91 (89 in SR, 2 in AF) runs of AF detection were performed using the nominal and modified parameters, respectively. The IAD detected AF and SR accurately, except for one episode of false-positive AF detection during sinus tachycardia at the nominal settings, but inappropriate shocks were prevented by minimum RR interval criteria that limited discharge at high heart rate. These results indicate that the AF detection algorithm in the IAD may become more vulnerable to false-positive AF detection during sinus tachycardia, which were avoided by reprogramming the Quiet Interval and minimum RR interval criteria for AF detection. Exercise testing appeared useful to program optimal settings of the IAD in preparation for daily activities. PMID- 9990641 TI - Transvenous atrial cardioversion threshold in patients with implantable cardioverter defibrillator: influence of active pectoral can. AB - Recent studies have shown that transvenous atrial cardioversion is feasible with lead configurations primarily designed for implantable cardioverter defibrillators (ICD). The purpose of this study was to examine the influence of an active pectoral ICD can on the atrial cardioversion threshold (ADFT). Forty consecutive patients received a transvenous single lead system (Endotak DSP 0125, CPI, St. Paul, MN, USA) in combination with a left subpectoral ICD (Ventak Mini, CPI) for treatment of malignant ventricular tachyarrhythmias. Patients were randomized into two groups: 21 received a Hot Can 1743 and 19 patients a Cold Can 1741. Step-down testing of the ventricular defibrillation threshold (VDFT) was performed intraoperatively and evaluation of the ADFT for induced atrial fibrillation (AF) at predischarge. After testing, each patient received a 2-J shock and was asked to quantify discomfort on a numerical scale ranging from 0 to 10. Both groups were comparable with regard to all clinical parameters studied. The mean VDFT in patients with a Hot Can device was significantly lower than in patients with a Cold Can (7.5 +/- 2.3 J vs 9.8 +/- 3.8 J; P < 0.03). The mean ADFT in the Hot Can group tended to be lower than in the group with Cold Cans (3.4 +/- 1.4 J vs 4.5 +/- 2.4 J; P = 0.07), and the proportion of patients in whom atrial cardioversion was accomplished at low energies (< or = 3 J) was higher in patients with active compared with patients with inactive pulse generators (57% vs 26%; P < 0.04). The mean discomfort reported after delivery of a 2-J shock was comparable in both groups (Hot Can 5.2 +/- 1.9; Cold Can: 5.3 +/- 2.1; P = NS). We conclude that the inclusion of an active left subpectoral can in the defibrillation vector of a ventricular ICD seems to reduce the energy requirements for atrial cardioversion without increasing the discomfort caused by low energy shocks. PMID- 9990642 TI - Mesenteric lymph node T cells but not splenic T cells maintain their proliferative response to concanavalin-A following peroral infection with Toxoplasma gondii. AB - The suppression of T cell responsiveness which occurs after infection with Toxoplasma gondii in mice has been widely studied using spleen cells. Because the natural route of infection with T. gondii is the peroral route, we examined the proliferative responses of mesenteric lymph node (MLN) cells, in addition to spleen cells, to Concanavalin-A (Con-A) in mice perorally infected with T. gondii. Proliferative responses of spleen cells were significantly suppressed seven and ten days after infection when compared with spleen cells from uninfected mice (62% and 91% reduction, respectively). In contrast, proliferative responses of MLN cells from these infected mice did not differ from those of normal MLN cells. Since IFN-gamma-induced reactive nitrogen intermediate (RNI) production has been reported to play a major role in suppression of proliferative responses in spleen cells of infected mice, we compared production of IFN-gamma and RNI by spleen and MLN cells following infection. MLN cells produced as much IFN-gamma as did spleen cells, but produced 70% less nitrite (as a measure of RNI) after Con-A stimulation. Proliferative responses of MLN cells were suppressed when co-cultured with spleen cells from infected mice, and addition of an inhibitor of RNI to these co-culture inhibited this suppression, suggesting that reduced RNI production by MLN cells contributes to their maintenance of higher proliferative responses. These results demonstrated a clear difference in activity of T cells in the MLN and spleen during the acute stage of the infection. PMID- 9990643 TI - Schistosoma japonicum myosin: cloning, expression and vaccination studies with the homologue of the S. mansoni myosin fragment IrV-5. AB - The Schistosoma japonicum homologue of the 62 kDa fragment of S. mansoni myosin (SmIrV-5), which has proved highly protective against S. mansoni infection in mice and rats, has been cloned and expressed as the full length 62 kDa equivalent, Sj62, and a truncated 44 kDa version, Sj44. DNA sequencing showed the Sj62 sequence to be 88.4% identical at the nucleic acid level and 96% identical in deduced amino acid sequence to that of SmIrV-5. The recombinant proteins (rSj44 and rSj62) were strongly recognized in Western blotting by sera from mice multiply vaccinated with UV-irradiated S. japonicum cercariae and weakly recognized by S. japonicum chronic infection mouse sera. Unlike SmIrV-5, mouse antisera against the recombinant S. japonicum proteins did not give positive recognition in immunofluorescence assay with the surface of newly transformed schistosomula of the homologous species, S. japonicum, nor did they react with S. mansoni schistosomula. However, the anti-rSj62 sera clearly localized the native antigen to the subtegumental muscle layers in male adult worm sections by immunoelectron microscopy. Vaccination of several groups of mice and/or rats with rSj44 and rSj62 incorporated into different adjuvants induced high titres of specific IgG but in only one experimental group was there a significant reduction in worm burden (27%, P < 0.05). The possible reasons for the disparity between the vaccination results presented here and those demonstrated in experiments using rSm62 (IrV-5) are discussed. PMID- 9990644 TI - Changes in specific anti-egg antibody levels following treatment with praziquantel for Schistosoma haematobium infection in children. AB - Fifty-seven children 6-15 years old resident in a Schistosoma haematobium endemic area in eastern Zimbabwe were treated with praziquantel at 40 mg/kg body weight. Levels of IgA, IgE, IgG1, IgG2, IgG3, IgG4, and IgM antibodies against soluble egg antigen (SEA) were assayed by ELISA before treatment and at 18 and 36 weeks following treatment. Prevalence of infection (as determined by urine egg counts) was 65% before treatment, all children were confirmed egg negative six weeks after treatment, and reinfection prevalence was 4% at 18 weeks and 21% at 36 weeks after treatment. At 18 weeks after treatment, there was a massive increase in IgG1 levels and significant increases in IgE and IgG4 levels and significant decreases in IgA and IgG2 levels. Similar patterns occurred at 36 weeks after treatment. Egg positive children showed a more marked increase in IgG1 and (for older children) a more marked decrease in IgG2 levels. There were no other effects of age or sex. IgA and IgG1 levels fell significantly between 18 and 36 weeks following treatment but not to pretreatment levels. The results show that specific anti-egg antibody responses are highly sensitive to the effects of praziquantel treatment. A possible consequence is that the susceptibility of children to infection with S. haematobium is altered by chemotherapy; this requires further investigation. PMID- 9990645 TI - Heligmosomoides polygyrus immunomodulatory factor (IMF), targets T-lymphocytes. AB - Experiments were performed to investigate the immunological site of action of an immunomodulatory factor (IMF), isolated from the gastrointestinal nematode Heligmosomoides polygyrus. IMF inhibited antibody production in murine and human 'T-helper (Th-2) driven' immunoassays. The effects were mediated via T lymphocytes as T cell-depleted cultures failed to respond to IMF, a result confirmed by prepulsing discrete cell subsets with the immunomodulant. Although the molecular nature and mode of action of IMF has yet to be determined, it would appear to be a relatively small non-proteinaceous molecule. From this data, we suggest that H. polygyrus secretes a systemically-active IMF from the intestinal lumen, to down-regulate Th-2 cell development in order to promote its survival in a potentially immunologically hostile environment. PMID- 9990646 TI - Characterization of variable immunodominant antigens of Cowdria ruminantium by ELISA and immunoblots. AB - Cross-immunization experiments have revealed a significant antigenic diversity of the isolate of Cowdria ruminantium which needs to be characterized for the development of vaccines. We identified polymorphic immunodominant antigens by ELISA and immunoblot. Using serum from a goat immune to the Gardel stock of Cowdria (isolated in Guadeloupe) adsorbed on antigen of the Senegal stock of this pathogen, distinct serogroups were revealed by ELISA among six isolates from different geographical origins. Furthermore, a goat serum directed against the Senegal stock and adsorbed on Gardel antigens was shown to be specific for the Senegal stock, thus confirming the existence of serotypes in Cowdria. The Major Antigenic Protein 1 (MAP1) of Cowdria was shown to have variable antigenic determinants. Also in a group of variable proteins ranging from 23 to 29 kDa, one antigen of 26-27 kDa had a determinant specific for the Gardel isolate. These polymorphic antigens may be relevant components of Cowdria ruminantium for a vaccine as the sera revealing these antigens originated from a goal surviving a lethal challenge. However, the presence of T-cell epitopes and the ability of the these antigens to confer protection to ruminants remain to be investigated. The production of a rabbit antiserum against this group of polypeptides will be of great use for their purification and for the screening of expression libraries. PMID- 9990647 TI - Intestinal and systemic humoral immunological events in the susceptible Balb/C mouse strain after oral administration of Echinococcus multilocularis eggs. AB - The aim of the study was to investigate the systemic and, for the first time, the intestinal humoral events in the susceptible Balb/C mouse strain after oral administration of Echinococcus multilocularis eggs. Thirty-one mice were divided into three groups; W-2, W-8 and control group. Each mouse of the W-2 and W-8 groups was orally infected with 1,500 E. multilocularis eggs, two weeks and eight weeks before sacrifice respectively. Control group mice received phosphate buffer saline. Measurement of anti-E. multilocularis and non-specific IgG, IgA and IgM, and of a transudation marker, albumin, were performed in serum and intestinal washings by a time-resolved immunofluorometric assay. These results were complemented by microscopic examination of the intestinal mucosa. This infection model is well-suited to the study of mucosal immunity during alveolar echinococcosis. It showed a major specific intestinal response in the early stage of the disease whereas the systemic response predominated later in the disease. Histopathological studies and calculation of the relative coefficient of excretion of Ig also confirmed that the presence of the parasite, even during a short period, was responsible for a local immunological and inflammatory response and for a change in mucosal permeability. Mucosal immunity could thus play a role in tolerance induction against E. multilocularis that could be a prerequisite for the subsequent development of the larvae in the liver, and for the occurrence of the parasitic disease, alveolar echinococcosis. PMID- 9990648 TI - Interferon-gamma signal transduction during parasite infection: modulation of MAP kinases in the infection of human monocyte cells (THP1) by Toxoplasma gondii. AB - We assayed mitogen-activated protein (MAP) kinase phosphorylation in a human monocyte cell line (THP1) during their infection by Toxoplasma gondii. In addition, we tested the effect of specific MAP kinase inhibitors (PD098059 and SB203580) on parasite invasion. MAP kinase phosphorylation was increased in the cytosol and membrane fractions of THP1 infected with T. gondii. The MAP kinase phosphorylation of uninfected THP1 cells was not significantly modified by incubation for 20 h with 1000 U/ml of IFN-gamma. However, IFN-gamma treatment of infected cells significantly reduces the increase in phosphorylation caused by parasite infection. There was also MAP kinase activity in the cytosol and membrane fractions of extracellular T. gondii tachyzoites. IFN-gamma altered the distribution of activity in subcellular fractions of extracellular T. gondii tachyzoites. This indicates that IFN-gamma directly affects parasite MAP kinase activity. The results provide evidence that MAP kinase pathways participate in the infection by T. gondii and that the decrease in MAP kinase activity in infected cells caused by IFN-gamma may be involved in mediating their protective signals. PMID- 9990649 TI - Cardiovascular activity of 14-deoxy-11,12-didehydroandrographolide in the anaesthetised rat and isolated right atria. AB - The cardiovascular activity of 14-deoxy-11,12-didehydroandrographolide (DDA) from Andrographis paniculata (Burm.f.) Nees (Acanthaceae) was elucidated in anaesthetised Sprague-Dawley (SD) rats and isolated rat right atria. In anaesthetised rats, DDA produced significant falls in mean arterial blood pressure (MAP) and heart rate in a dose-dependent manner with the maximum decrease of 37.6 +/- 2.6% and 18.1 +/- 4.8%, respectively. The ED50 value for MAP was 3.43 mmol kg-1. Pharmacological antagonist studies were done using this dose. The hypotensive action of DDA was not mediated through effects on the alpha adrenoceptor, muscarinic cholinergic and histaminergic receptors, for it was not affected by phentolamine, atropine as well as pyrilamine and cimetidine. However, it seems to work via adrenoceptors, autonomic ganglia receptor and angiotensin converting enzyme, since the hypotensive effect of DDA was negated or attenuated in the presence of propranolol, hexamethonium and captopril. In the isolated right atria, DDA caused negative chronotropic action and antagonised isoproterenol-induced positive chronotropic actions in a non-competitive and dose dependent manner. These results further supported the bradycardia-inducing and beta-adrenoceptor antagonistic properties of DDA in vivo. PMID- 9990650 TI - Pharmacology of nebivolol. AB - Nebivolol is a new selective beta 1-adrenergic blocking agent, that possesses a peculiar pharmacodynamic profile and an original chemical structure, by which it differs from traditional beta 1-blockers. Nebivolol is a racemic mixture of two enantiomers in equal ratios. It is endowed with a highly selective beta 1 blocking activity, and does not show an intrinsic sympathomimetic activity. Nebivolol is endowed with peripheral vasodilating properties mediated by the modulation of the endogenous production of nitric oxide. It does not significantly decrease airway conductance compared with atenolol and propranolol. Nebivolol does not compromise the left ventricular function, but it may increase stroke volume, and does not reduce heart inotropism during exertion. Nebivolol is quite safe and is well tolerated, also when compared to traditional beta blockers. The most common adverse effects are dizziness, headache and fatigue. Owing to its combined dual mechanism of action, nebivolol leads to a unique haemodynamic and therapeutic profile by which it may be advantageous in essential hypertension, ischaemic heart disease and congestive heart failure. PMID- 9990651 TI - Effects of free radical production and scavengers on occlusion-reperfusion induced arrhythmias. AB - Ventricular arrhythmias were studied in rat isolated hearts subjected to coronary artery occlusion and reperfusion. Free radicals in the perfusate were detected by continuous flow luminol-enhanced chemiluminescence. Administration of purine (2.3 mM) and xanthine oxidase (0.12 U ml-1 min-1) did not significantly modify the severity of reperfusion-induced arrhythmias but did generate free radicals. No free radical generation was detected during the period of coronary artery occlusion or reperfusion. Superoxide dismutase (SOD) 20-80 U ml-1 did not alter the severity of reperfusion arrhythmias but, in the presence of 80 U ml-1 SOD, occlusion-induced arrhythmias were augmented. SOD did not produce any effect on haemodynamics at the concentrations tested. Ventricular arrhythmias and cardiac haemodynamics were also not significantly changed by the combination of scavengers, SOD (10 U ml-1), catalase (100 U ml-1) and mannitol (20 mM). These data suggest that the superoxide free radical is unlikely to be the primary cause of reperfusion induced arrhythmias in rat isolated hearts subjected to regional ischaemia. PMID- 9990652 TI - Potentiation of muscimol-induced long-term depression by benzodiazepines and prevention or reversal by pregnenolone sulfate. AB - We have recently reported a new protocol for inducing long-term depression through activation of GABAA receptors in the hippocampal slices. This long-term depression is reversed by bicuculline and potentiated by neurosteroids such as alphaxalone. It was also shown that glutamate receptor activity or extracellular calcium are not involved in the induction of this type of long-term depression. The present study investigated the possible relation between muscimol-induced long-term depression and barbiturates/benzodiazepine-induced amnesia and attempts to determine the possible effect of pregnenolone sulfate on muscimol-induced long term depression. Extracellular recordings were made in the CA1 pyramidal cell layer of rat hippocampal slices following orthodromic stimulation of Schaffer collateral fibres in stratum radiatum (0.01 Hz). It was observed that pentobarbital, benzodiazepines and pregnanolone at concentrations that did not have any effect themselves on the population spike, potentiate the ability of muscimol to induce long-term depression. In addition to this, the long-term depression was either blocked or reversed by pregnenolone sulfate at concentrations (10 microM) where pregnenolone sulfate did not induce any multiple burst or increase of spike size. The results suggest that the potentiation of this type of long-term depression by benzodiazepines and barbiturates can explain the main adverse effect of these drugs, amnesia and cognitive impairment. Moreover, the prevention or reversal of this type of long-term depression by pregnenolone sulfate, may suggest a clinical application of this agent in the management of amnesia or dementia. PMID- 9990653 TI - Effect of propranolol and nifedipine on maximal electroshock-induced seizures in mice: individually and in combination. AB - A comparative effect of propranolol and nifedipine administered individually and in combination at graded dose levels; and that of phenytoin at 30 mg kg-1 on maximal electroshock (MES)-induced seizure in mice was investigated. Propranolol in doses of 10 mg kg-1 and 20 mg kg-1, and nifedipine in doses of 8 mg kg-1 and 16 mg kg-1 significantly modified MES activity. Propranolol (40 mg kg-1), and a combination of propranolol (20 mg kg-1) and nifedipine (8 mg kg-1), produced antiMES activity, which was comparable to that of phenytoin (30 mg kg-1). In mice treated with propranolol and nifedipine combination, the tonic flexor and tonic extensor phase ratios (F/E ratio) were significantly higher than individual drug responses. Our findings suggest that a combination of propranolol and nifedipine has either synergistic or an additive effect in controlling MES-induced seizures in mice. PMID- 9990654 TI - ACEA-1328, an NMDA receptor antagonist, increases the potency of morphine and U50,488H in the tail flick test in mice. AB - The effect of 5-nitro-6,7-dimethyl-1,4-dihydro-2,3-quinoxalinedione (ACEA-1328), a competitive and systemically bioavailable NMDA receptor/glycine site antagonist, was examined on opioid-induced antinociception in the tail flick test. Swiss Webster mice were injected with ACEA-1328 either alone or in combination with morphine or (+/-)-trans-U-50488 methanesulfonate (U50,488H), a mu- and a kappa-opioid receptor agonist, respectively, and tested for antinociception. Systemic administration of ACEA-1328 alone increased the tail flick latencies with an ED50 of approximately 45 mg kg-1. Concurrent administration of ACEA-1328 with morphine, or U50,488H, at doses that did not affect tail flick latencies, potentiated the antinociceptive effect of the opioid analgesics and vice versa. Naloxone, an opioid receptor antagonist, while not modifying the effect of ACEA-1328, did block the augmentation, suggesting that opioid receptors might be involved in the latter effect. 5-Aza-7-chloro-4-hydroxy 3-(m-phenoxyphenyl)quinoline-2(1H)-one (ACEA-0762), a selective NMDA receptor/glycine site antagonist, also showed enhancement of the antinociceptive effect of morphine and U50,488H. However, concurrent administration of 2,3 dihydroxy-6-nitro-7-sulfamoyl-benzol[f]quinoxaline (NBQX), a selective non-NMDA receptor antagonist, with morphine did not alter the antinociceptive potency of the opioid analgesic. Overall, the data suggest that ACEA-1328 may increase the potency of the opioid analgesics by antagonising the glycine site associated with the NMDA receptor. PMID- 9990655 TI - CGP 42112A antagonism of the angiotensin II and angiotensin II(3-7) facilitation of recall in rats. AB - An involvement of the angiotensin AT2 receptors in some behavioural effects of angiotensin II (Ang II) and its 3-7 fragment [Ang II(3-7)] in rats was studied. To inhibit AT2 receptors we used their selective antagonist CGP 42112A (nicotinic acid-Tyr-N-benzoxyl-carbonyl-Arg-Lys-His-Pro-Ile-OH). Ang II and Ang II(3-7), given intracerebroventricularly (i.c.v.) at the dose of 1 nmol each, significantly enhanced recall of the passive avoidance behaviour and learning of the conditioned avoidance responses (CARs). CGP 42112A (2 micrograms i.c.v.), inactive on its own in all tests, significantly attenuated facilitation of recall of passive avoidance caused by Ang II and Ang II(3-7). Also, CGP 42112A diminished Ang II improvement of CARs acquisition but not that caused by Ang II(3 7). None of the treatments produced significant anxiolysis in an elevated 'plus' maze. Likewise, in an open field no statistically significant differences were recorded except for the abolishment of the Ang II(3-7)-induced increase of rearings and bar approaches by CGP 42112A. It appears that the cognition improving activity of Ang II and Ang II(3-7) is mediated by similar mechanisms and angiotensin AT2 receptors are engaged in these processes. PMID- 9990656 TI - Effects of different antisecretory drugs on gastric potential difference in the rat: comparison with sucralfate. AB - The proton pump inhibitors omeprazole and lansoprazole and the histamine H2 receptor antagonists ranitidine and nizatidine were investigated for their effects on gastric transmucosal potential difference (PD) in the rat, in comparison with the gastroprotective compound sucralfate. Omeprazole (1-3 mg kg 1, i.v.) and lansoprazole (1-3 mg kg-1, i.v.) did not modify basal PD, but significantly reduced (by approx. 50-60%) the drop in PD caused by intragastric administration of acetylsalicylic acid (ASA, 60 mg kg-1). Ranitidine (3-100 mg kg 1, i.v.) and nizatidine (10-30 mg kg-1, i.v.) behaved similarly to proton pump inhibitors, being ineffective on basal PD, while significantly reducing the effect of ASA. The antisecretory compounds did not change basal pH values. Sucralfate (0.5-1.5 g kg-1 intragastrically) caused a slight increase (approx. 20%) of basal PD and a dose-dependent reduction of ASA-induced fall in PD, with a maximum effect (65% reduction) comparable to that caused by the antisecretory agents. These results showed that ASA-induced disruption of the mucosal barrier can be reduced to the same extent by various antiulcer drugs, irrespective of their effects on gastric acid secretion. PMID- 9990658 TI - Comparative bioavailability of two sustained-release theophylline formulations in the dog. AB - The kinetics of two sustained-release theophylline formulations, Theo-Dur (Recordati, Milano, Italy) and Diffumal (Malesci, Firenze, Italy) were studied in eight beagle dogs. In a first part of the study each animal was injected intravenously with aminophylline dihydrate, Aminomal (Malesci, Firenze, Italy), in order to determine the absolute bioavailability of the two sustained-release theophylline formulations orally administered to the dogs in the second experimental phase, over a period of 9 days, following a balanced two-period cross-over design. Assays for theophylline were performed by high performance liquid chromatography and the pharmacokinetic analysis was performed using the non-compartmental method. The principle of superposition was then applied to predict multiple dose plasma concentrations from experimental single dose data. No significant differences between the two preparations were found with respect to the main pharmacokinetic parameters, showing that the two preparations are bioequivalent. The fact that the differences between experimental and predicted results were not statistically significant allows us to conclude that multiple dose steady state plasma theophylline concentration in the dog can be predicted from experimental single dose data. Furthermore, after repeated treatment, both Diffumal and Theo-Dur, given twice daily are able to maintain therapeutic (5-20 mg ml-1) plasma theophylline concentrations in the dog. PMID- 9990657 TI - Involvement of PACAP in acid-induced HCO3- response in rat duodenums. AB - Pituitary adenylate cyclase activating polypeptides (PACAP) stimulate duodenal HCO3- secretion in the rat. The present study was performed to determine whether endogenous PACAP is involved in the mechanism of acid-induced HCO3- response in the duodenum, using a PACAP antagonist, PACAP6-27. Under urethane anaesthetised conditions, a duodenal loop that was made between the pylorus and the area just above the outlet of the common bile duct was perfused with saline, and the HCO3- secretion was measured at pH 7.0 using a pH-stat method and by adding 10 mM HCl. Duodenal HCO3- secretion was significantly stimulated by i.v. administration of PACAP-27 (8 nmol kg-1) as well as vasoactive intestinal polypeptide (VIP: 8 nmol kg-1). The effect of PACAP-27 (8 nmol kg-1) was equivalent to that induced by prostaglandin E2 (300 micrograms kg-1, i.v.) and significantly suppressed by either PACAP6-27 (40 nmol kg-1, i.v.) or VIP antagonist (Ac-Tyr1, D-Phe2-VIP: 40 nmol kg-1, i.v.). These peptide antagonists suppressed duodenal HCO3- secretory response to VIP but did not have any effect on either basal or PGE2-stimulated HCO3- secretion. On the other hand, the duodenal mucosa responded to acidification by increasing HCO3- secretion in a indomethacin-sensitive manner, and this process was also significantly suppressed by both PACAP6-27 and VIP antagonist. Duodenal damage induced by acid perfusion (100 mM HCl for 4 h) was significantly worsened by PACAP6-27, VIP antagonist as well as indomethacin at the doses that suppressed acid-induced HCO3- secretion. These findings suggest that PACAP may play a role in local modulation of the duodenal mucosal integrity, by mediating the HCO3- secretory response induced by mucosal acidification. PMID- 9990659 TI - Anti-allergic and anti-anaphylactic activity of picroliv--a standardised iridoid glycoside fraction of Picrorhiza kurroa. AB - Picroliv, a standardised iridoid glycoside fraction from the root and rhizome of Picrorhiza kurroa at a dose of 25 mg kg-1 p.o. inhibited passive cutaneous anaphylaxis in mice (82%) and rats (50-85%) and protected mast cells from degranulation (60-80%) in a concentration-dependent manner. Its effect was also studied in sensitised guinea pig ileum preparation in vitro (Schultz-Dale study) and in normal guinea pigs in vivo (Konzett-Rossler, in preparation). There was inhibition of the Schultz-Dale response in sensitised guinea pig ileum, but the bronchospasm induced by histamine could not be antagonised or prevented by Picroliv, indicating the absence of a direct post-synaptic histamine receptor blocking activity. PMID- 9990660 TI - Dual role of betel leaf extract on thyroid function in male mice. AB - The effects of betel leaf extract (0.10, 0.40, 0.80 and 2.0 g kg-1 day-1 for 15 days) on the alterations in thyroid hormone concentrations. lipid peroxidation (LPO) and on the activities of superoxide dismutase (SOD) and catalase (CAT) were investigated in male Swiss mice. Administration of betel leaf extract exhibited a dual role, depending on the different doses. While the lowest dose decreased thyroxine (T4) and increased serum triiodothyronine (T3) concentrations, reverse effects were observed at two higher doses. Higher doses also increased LPO with a concomitant decrease in SOD and CAT activities. However, with the lowest dose most of these effects were reversed. These findings suggest that betel leaf can be both stimulatory and inhibitory to thyroid function, particularly for T3 generation and lipid peroxidation in male mice, depending on the amount consumed. PMID- 9990661 TI - Correlation of skin phototype with facial wrinkle formation. AB - Facial wrinkle formation is a representative sign of photoaging. Skin can be divided into different skin phototypes (SPTs) depending on its sensitivity to solar radiation. We have determined the relationship between SPTs and deep and fine wrinkle scores on the faces of 230 Japanese subjects. This group was chosen because it is relatively easy to quantify acute and chronic sun damage in Japanese individuals. SPT in the Japanese subjects was classified into one of four groups, SPT-I to -IV according to Fitzpatrick's classification method. The subjects were further classified into indoor or outdoor workers. After photographing the outer canthus, deep and fine wrinkles were discriminated visually and scored from 1-11 and from 1-9, respectively. UV light was used as a photographic light source for clear depiction of the fine wrinkles. Higher scores were recorded for deep wrinkles in individuals with SPT-I, who are more sensitive to sunlight than those with SPT-III or IV, who are more tolerant to sunlight. However, the same tendency did not seem to be apparent for fine wrinkle scores. A high incidence of SPT-IV was seen in outdoor workers. Early detection of SPT-I in individuals who are sensitive to sunlight, may help to predict and prevent photoaging of deep wrinkles. Sensitivity to sunlight may play a part in determining an individual's choice of working environment. PMID- 9990662 TI - Phototesting in oriental patients with lupus erythematosus. AB - Light sensitivity is an important clinical characteristic of several forms of lupus erythematosus (LE). Recently, investigations have been able to induce LE like lesions in LE patients with UVA as well as UVB, although most of these studies were conducted in Caucasians. Thus, there is insufficient data on phototesting in Oriental patients with LE. The aim of this study was to evaluate light sensitivity in Oriental patients with LE. Fifteen patients with various forms of LE were tested. Patients were evaluated by provocative phototesting, and threshold doses of UVA and UVB radiation that produced erythema and pigmentation were determined. The minimal erythema doses (MED) of UVB, immediate pigment darkening (IPD), and minimal tanning doses (MTD) were within the normal range in LE patients compared to a control group. Skin lesions clinically and histologically compatible with LE were induced in two of six patients with SLE, and four of nine patients with DLE. These lesions developed in about 2 weeks (range 5 to 23 days) after irradiation and lasted approximately 1 to 3 months (47 +/- 24 days). The action spectrum of the induced lesions was within the UVB range in four patients, in the UVA range in one patient, and in the UVB and UVA ranges in one patient. We found no correlation between a positive history for UV sensitivity and phototest reactions. In conclusion, the incidence of positive phototest reactions in Oriental patients with LE seems to be similar to or a little lower than in Caucasians. There was no correlation between a positive history for UV sensitivity and phototest reactions. PMID- 9990663 TI - In vitro and in vivo activation of hypericin with the incoherent light source PDT 1200 SOA (520-750 nm) and with solar simulated radiation (290-2500 nm). AB - The photodynamic active plant pigment hypericin is a possible new photosensitizer for photodynamic therapy. Hypericin shows absorption maxima in the ultraviolet (330 nm) and visible light range (550 and 588 nm). The present study compared the photoactivation of hypericin with the incoherent light source PDT 1200 SOA (520 750 nm) to that with a 1000 watt solar simulator (290-2500 nm). Hypericin displayed dose and time dependent phototoxic effects in the keratinocyte cell line HaCaT in vitro and after intracutaneous in vivo application with both light sources. In vivo, delayed (48 h) photosensitivity in hypericin-sensitized skin was observed. With intracutaneous application of 100 ng/ml hypericin, no phototoxic reaction could be produced. The PDT 1200 SOA was about four times more effective in vitro and about ten times more effective in vivo when compared to the solar simulator. Since the PDT 1200 SOA allows homogenous irradiation of large areas, we conclude that the PDT 1200 SOA is an effective and convenient light source for in vitro and in vivo studies using hypericin. PMID- 9990664 TI - Induction of complete wound healing in recalcitrant ulcers by low-intensity laser irradiation depends on ulcer cause and size. AB - Chronic skin ulcers still represent a therapeutic challenge in dermatology. Among the various non-invasive treatment modalities used for the improvement of impaired wound healing, low-intensity laser irradiations are gaining an increasing body of interest. We used low-intensity laser irradiations delivered by a 30 mW helium-neon laser at an energy density of 30 J/cm2 three times weekly for the induction of wound healing in ulcers of diverse causes. Twenty patients with the same number of ulcers, which had previously been treated by conventional wound care for a median period of 34 weeks (range: 3-120 weeks) without any significant evidence of healing, were included in the study. Concerning the underlying disorders, patients were divided into four groups: diabetes, arterial insufficiency, radio damage and autoimmune vasculitis. In all ulcers, complete epithelization could be induced by laser therapy. No amputation or any other surgical intervention was necessary and no adverse effects of any kind were noted during low-intensity laser treatment. Regarding the different diagnoses, a statistically significant difference was noted (P = 0.008): ulcers due to radio damage healed significantly faster than those caused by diabetes (6 weeks [range: 3-10 weeks] vs. 16 weeks [range: 9-45 weeks], P = 0.005). Wound healing in autoimmune vasculitis (24 weeks [range: 20-35 weeks]) required longer than in radiodermitis, although the difference was not significant. In addition to the diagnosis, wound size was found to be an important factor influencing the duration of wound closure (P = 0.028), whereas duration of previous conventional treatment (P = 0.24) and depth (P = 0.14) showed no effect. Our results indicate that low-intensity laser irradiation could be a valuable non-invasive tool for the induction of wound healing in recalcitrant ulcers, and that healing time is correlated with the ulcer cause and size. PMID- 9990665 TI - PUVA-induced lymphocyte apoptosis: mechanism of action in psoriasis. AB - Psoralen plus ultraviolet A (PUVA), utilizing oral 8-methoxypsoralen (8-MOP), is a widely utilized and effective treatment for psoriasis vulgaris. Previous studies have suggested that PUVA's mechanism of action in psoriasis is a result of its direct lymphotoxic effects. Trimethylpsoralen (TMP), a potentially safer compound, has been found to be effective in psoriasis during bath water delivery. In this study we examined the relative antilymphocytic effects of TMP and 8-MOP through both flow cytometry and tissue analysis on lesional skin during clinical treatment. Based on FACS analysis on phytohemagglutinin-activated lymphocytes, we found TMP to be nearly 10,000 fold more lymphotoxic compared to 8-MOP. In addition, lymphocytes treated with 8-MOP or TMP with UVA displayed DNA degradation patterns typical of apoptotic cell death. These findings were consistent with our investigation of treated psoriatic skin, with virtual elimination of epidermal CD3+ T-cells following bath water treatment with TMP or 8-MOP. These results support the theory that the therapeutic effects of PUVA stem from its toxic effects on activated lymphocytes. If further investigation supports TMP's lack of carcinogenicity, this potent lymphotoxic treatment may prove to be one of the safest and most effective treatments for psoriasis. PMID- 9990666 TI - HIV, UV and immunosuppression. AB - Cutaneous diseases are common manifestations of infection with human immunodeficiency virus (HIV). Phototherapy with ultraviolet B (UVB) and photochemotherapy with 8-methoxypsoralen plus UVA (PUVA) have been used successfully to treat several of these skin conditions, including psoriasis, folliculitis, pruritus, and eczema. However, in view of the known immunosuppressive effects of UV radiation, concerns have been raised about potential adverse effects of UV on persons infected with HIV. In the following report, we review the effects of UV in HIV-infected cell lines in vitro, in animal models, as well as in human studies. Based on currently available data, UV radiation, as used in phototherapy and photochemotherapy, appears to have no adverse effects in HIV-infected individuals. PMID- 9990667 TI - Recent developments in fluoroquinolone phototoxicity. PMID- 9990668 TI - Sunblocks: mechanisms of action. PMID- 9990669 TI - Malignant melanoma in patients treated for psoriasis with PUVA. PMID- 9990670 TI - Are we teaching phototherapy? Results of an informal survey of phototherapy education. PMID- 9990671 TI - Discussion of a case of vitiligo. PMID- 9990672 TI - Inhibition by tocopherol of prostaglandin-induced apoptosis in ovine corpora lutea. AB - Accumulation of toxic oxidants within corpora lutea is a prelude of apoptotic cell death. Vitamin E (alpha-tocopherol) is a biological antioxidant that protects cells from the inductive effects of reactive oxygen on DNA damage and nuclear/cytoplasmic condensation that dictate apoptosis. Ewes were challenged with a luteolytic dose of PGF2 alpha on d 10 of the estrous cycle. The acute decline in circulatory progesterone indicative of the onset of functional luteolysis was not affected by systemic administration of alpha-tocopherol; however, corpora lutea consequently (beyond 24 h) rebounded from the steroidogenic insult. Luteal tissues obtained at 24 h after PGF2 alpha revealed that internucleosomal DNA fragmentation and cellular collapse were inhibited by alpha-tocopherol. These observations indicate that regressive corpora lutea can be spared from terminal involution by diminishing the apoptotic influence of luteolytic hormone with an antioxidant. PMID- 9990673 TI - Lipopolysaccharide-induced expression of cyclooxygenase-2 in mouse macrophages is inhibited by chloromethylketones and a direct inhibitor of NF-kappa B translocation. AB - In macrophages, cyclooxygenase-2 (COX-2) is induced by cytokines, mitogens, or endotoxin. The present study investigates whether inhibitors of the nuclear transcription factor NF-kappa B affect lipopolysaccharide (LPS)-mediated expression of COX-2 mRNA, protein, and activity in the macrophage cell line J774.1A. The activation of COX-2 was assessed by measuring the accumulation of prostaglandin (PG) E2 by radioimmunoassay. Expression of COX-2 mRNA and protein was detected by Northern and Western blot analysis, respectively. In the absence of LPS, mouse macrophages did not express COX-2 and generated low amounts of prostaglandin (PG) E2. Treatment of J774.1A with LPS (0.1-30 micrograms/ml) caused expression of COX-2 protein and activity. Induction of COX-2 activity along with the induction of COX-2 mRNA and protein by LPS was attenuated by the serine protease inhibitors N-alpha-tosyl-L-phenylalanine chloromethyl ketone (TPCK) and N-alpha-tosyl-L-lysine chloromethyl ketone (TLCK). A cell permeable peptide and a direct inhibitor of NF-kappa B translocation, SN50, attenuated the accumulation of PGE2 in cell supernatant in a concentration-dependent manner. Our results show that induction of COX-2 by LPS in macrophages involves activation of NF-kappa B and point to a possible therapeutic use of protease inhibitors in inflammatory processes. PMID- 9990674 TI - Mice deficient for 5-lipoxygenase, but not leukocyte-type 12-lipoxygenase, display altered immune responses during infection with Schistosoma mansoni. AB - Periovular granuloma formation during Schistosoma mansoni infection is a complex, multifaceted immunologic response. Products of arachidonic acid metabolism have been shown to contribute to this response through studies in which general inhibitors of lipoxygenase function reduce granulomatous inflammation. To determine which lipoxygenases are important for granuloma development in schistosomiasis, wild type mice or mice deficient for 5-lipoxygenase (5-LO) or "leukocyte-type" 12-lipoxygenase (12-LO) were infected with S. mansoni and studied for responses to schistosome eggs and egg antigens. At the acute stage of infection, when granuloma formation is usually maximal, 5-LO deficient mice developed smaller granulomas around liver-deposited schistosome eggs compared with wild type or 12-LO deficient mice. 5-LO mice also displayed less antibody mediated (5 h) and cell-mediated, delayed-type (24 h) hypersensitivity to schistosome egg antigens than did the other two infection groups. In an attempt to determine possible mechanisms for the reduced inflammatory responses, we also measured hepatic mRNA levels of cytokines that have been shown to influence granuloma size (IL-4, IL-10, and IFN-gamma). The mRNA levels for IL-10 were significantly lower in 5-LO-deficient mice, but SEA-stimulated spleen cells did not demonstrate a significant difference in IL-10 production between wild type and 5-LO mice. These data suggest that 5-LO plays a role in host responses to schistosomiasis via a mechanism that cannot be explained solely by changes in expression of these cytokines. PMID- 9990675 TI - Identification and pharmacological characterization of platelet-activating factor and related 1-palmitoyl species in human inflammatory blistering diseases. AB - Through its pro-inflammatory effects on leukocytes, endothelial cells, and keratinocytes, the lipid mediator platelet-activating factor (PAF) has been implicated in cutaneous inflammation. Although the 1-alkyl PAF species has been considered historically the most abundant and important ligand for the PAF receptor (PAF-R), other putative ligands for this receptor have been described including 1-acyl analogs of sn-2 acetyl glycerophosphocholines. Previous bioassays have demonstrated a PAF-like activity in lesions of the autoimmune blistering disease bullous pemphigoid. To assess the actual sn-2 acetyl glycerophosphocholine species that result in this PAF agonistic activity, we measured PAF and related sn-2 acetyl GPCs in fresh blister fluid samples from bullous pemphigoid and noninflammatory (suction-induced) bullae by mass spectrometry. We report the presence of 1-hexadecyl as well as the 1-acyl PAF analog 1-palmitoyl-2-acetyl glycerophosphocholine (PAPC) in inflammatory blister fluid samples. Because PAPC is the most abundant sn-2 acetyl glycerophosphocholine species found in all samples examined, the pharmacological effects of this species with respect to the PAF-R were determined using a model system created by transduction of a PAF-R-negative epidermoid cell line with the PAF-R. Radioligand binding and intracellular calcium mobilization studies indicated that PAPC is approximately 100x less potent than PAF. Though a weak agonist, PAPC could induce PAF biosynthesis and PAF-R desensitization. Finally, intradermal injections of PAF and PAPC into the ventral ears of rats demonstrated that PAPC was 100x less potent in vivo. These studies suggest possible involvement of PAF and related species in inflammatory bullous diseases. PMID- 9990676 TI - Contribution of cyclooxygenase-1 and cyclooxygenase-2 to prostanoid formation by human enterocytes stimulated by calcium ionophore and inflammatory agents. AB - The stimulation of intestinal epithelial cell cyclooxygenase (COX) enzymes with inflammatory agents and the inhibition of COX-1 and COX-2 enzymes has the potential to increase understanding of the role of these enzymes in intestinal inflammation. The aim of this study was to determine the contributions of COX-1 and -2 to the production of specific prostanoids by unstimulated and stimulated intestinal epithelial cells. Cultured enterocytes were stimulated with lipopolysaccharide (LPS), interleukin-1 (IL-1)beta (IL-1 beta), and calcium ionophore (Ca Ion), with and without COX inhibitors. Valerylsalicylic acid (VSA) was employed as the COX-1 inhibitor, and SC-58125 and NS398 were used as the COX 2 inhibitors. Prostanoids were quantitated by Elisa assay. Western immunoblotting demonstrated the presence of constitutive COX-1 and inducible COX-2 enzyme. Unstimulated prostanoid formation was not decreased by the COX-1 inhibitor. All of the stimulants evaluated increased prostaglandin E2 (PGE2) production. Only Ca Ion stimulated prostaglandin D2 (PGD2) production while IL-1 beta, and Ca Ion, but not LPS, increased prostaglandin F2 alpha (PGF2 alpha) formation. Ca Ion stimulated prostanoid formation was uniformly inhibited by COX-2, but not COX-1, inhibitors. IL-1 beta-stimulated PGE2 and PGE2 alpha formation was significantly decreased by both COX-1 and COX-2 inhibitors. VSA, in a dose-dependent manner, significantly decreased IL-1 beta-stimulated PGE2 and PGF2 alpha production. Unstimulated prostanoid formation was not dependent on constitutive COX-1 activity. The stimulation of intestinal epithelial cells by Ca Ion seemed to uniformly produce prostanoids through COX-2 activity. There was no uniform COX-1 or COX-2 pathway for PGE and PGF2 alpha formation stimulated by the inflammatory agents, suggesting that employing either a COX-1 or COX-2 inhibitor therapeutically will have varying effects on intestinal epithelial cells dependent on the prostanoid species and the inflammatory stimulus involved. PMID- 9990677 TI - The advent of highly selective inhibitors of cyclooxygenase--a review. AB - Cyclooxygenase (COX) exists in two isoforms, COX-1 and COX-2, COX-1 is present and is constitutively expressed in most cells and tissues, whereas COX-2 is felt to principally mediate inflammation. However, this distinction appears to be challenged by recent observations. This review addresses the roles of COX-1 and COX-2 isoforms in physiologic and pathophysiologic states and reviews potential therapeutic roles for selective COX inhibitors. PMID- 9990678 TI - Types of purinoceptors and phospholipase A2 involved in the activation of the platelet-activating factor-dependent transacetylase activity and arachidonate release by ATP in endothelial cells. AB - Acyl analogs of PAF are the major products synthesized during agonist stimulation of endothelial cells. We have previously shown that PAF: 1-acyl-2-lyso-sn-glycero 3-phosphocholine transacetylase in calf pulmonary artery endothelial cells is activated by ATP through protein phosphorylation, and the increase in transacetylase activity by ATP contributes to the biosynthesis of acyl analogs of PAF (J. Biol. Chem. 272, 17431-17437, 1997). To understand the mechanisms(s) by which ATP stimulates acyl analogs of PAF production, we have identified the subtypes of the purinergic receptor that are linked to the activation of two enzymes involved in the generation of acyl analogs of PAF, namely, transacetylase and phospholipase A2. Experiments with transient transfection of the cells with antisense and sense thio-oligonucleotide to cytosolic phospholipase A2 (cPLA2) were also performed to evaluate whether downstream activation of cPLA2 is involved in ATP-receptor mediated induction of arachidonate release and synthesis of radylacetyl-GPC. We found that the P2u/P2Y2 receptor, which recognizes a pyrimidine nucleotide, UTP, as well as purine nucleotides, shows a potency profile of UTP > ATP = ATP gamma S > 2-methylthio-ATP in mediating the activation of PAF: lysophospholipid transacetylase. On the other hand, ADP beta S and 2 methylthio-ATP have similar potencies as ATP but have lower potencies than UTP and ATP gamma S in stimulating the release of arachidonate. These results suggest that both P2u/P2Y2 and P2y/P2Y1 receptor subtypes promote arachidonate release. In addition, transient transfection of endothelial cells with cPLA2 antisense but not the sense thio-oligonucleotide inhibited the stimulation of arachidonate release and [3H]acetate incorporation into radyl[3H]acetyl-GPC. Thus, our data suggest that a receptor-mediated process is involved in the activation of transacetylase for the induced synthesis of acyl analogs of PAF in endothelial cells. Furthermore, it is likely that cPLA2 supplies the lysophospholipids as substrates for the transacetylation reaction. PMID- 9990679 TI - Effects of elevated concentrations of prostaglandin F2 alpha on pregnancy rates in progestogen supplemented cattle. AB - An experiment was performed to determine the effect of elevated prostaglandin F2 alpha (PGF2 alpha) on pregnancy rates of progestogen-treated bred cows in the presence or absence of luteal tissue. Ninety-one beef cows were bred (Day 0) and assigned randomly to receive either 3 mL saline (CON), 15 mg PGF2 alpha, or 15 mg PGF2 alpha + lutectomy (P + L) administered intramuscularly (i.m.) at 8 h intervals on either Days 5-8, 10-13, or 15-18 postbreeding. Lutectomies were performed by transrectal digital pressure before initiation of treatment on Day 5, 10, or 15 for the respective treatment groups. All cows were fed 4 mg/day of melengesterol acetate from two days prior to initiation of treatment until Day 30 postbreeding. Mean concentrations of 13,14-dihydro-15-keto-PGF2 alpha (PGFM) were increased in cows administered PGF2 alpha and P + L treatments (398 +/- 23 and 413 +/- 22 pg/ml, respectively; p < 0.01) compared to the CON group (80 +/- 29 pg/ml) regardless of treatment group. Mean concentrations of oxytocin (OT) were increased in cows given PGF2 alpha on Day 10 and 15 (p < or = 0.0001) and tended to be increased on d 5 when compared to CON and P + L treatment groups on Day 5. Pregnancy rates were reduced (p < or = 0.03) in the PGF2 alpha treatment group (23%) and by Day 5-8 compared to CON (72%). Lutectomy tended to improve pregnancy rate in P + L (5-8; 55%) compared to PGF2 alpha (5-8; p = 0.1). Pregnancy rates tended (p < or = 0.07) to increase in the PGF2 alpha treatment groups on Days 5-8 treatment (23%, 50%, and 60% for Days 5-8, 10-13, and 15-18, respectively). The later the treatments were initiated pregnancy rates did not differ between treatments given on Days 10-13 and 15-18. In conclusion, the most susceptible period of embryonic growth to the negative effects of PGF2 alpha was during morula to blastocyst development. Removal of luteal tissue diminishes the negative effects of PGF2 alpha through interruption of the luteal oxytocin uterine PGF2 alpha feedback loop. PMID- 9990680 TI - Role and evaluation of mammography and other imaging methods for breast cancer detection, diagnosis, and staging. AB - Mammographic screening of women age 40 and older can reduce breast cancer deaths by at least 30% to 40%. However, not all cancers are detected by mammography. Although a new supplementary modality for screening could, in theory, fill in this detection gap, such utilization must be based on rigorous demonstration of its ability to consistently and frequently find early cancers missed by mammography, such as those occurring in dense breasts or rapidly growing interval cancers that surface clinically between mammographic screens. After an abnormality is found at mammographic screening, supplementary mammographic views and/or ultrasound are now used to match the finding with an ACR BIRADS final diagnostic assessment category to indicate the relative likelihood of a normal, benign, or malignant diagnosis so that routine screening, short interval follow up, or biopsy can then be advised. Appropriate categorization will maximize early cancer detection and minimize false-positive biopsies. Application of a new imaging method to this type of diagnostic evaluation requires well-designed studies to determine its effectiveness for this purpose. PMID- 9990681 TI - The role of 99mTc-sestamibi and other conventional radiopharmaceuticals in breast cancer diagnosis. AB - The wide availability and the extensive use of screening mammography have resulted in an earlier diagnosis of breast cancer and in a significant reduction in the relative risk of dying from this disease. Despite technical improvements and major advantages associated with the use of mammography (and breast ultrasound), this procedure has some limitations in clinical practice, especially in women with dense breast tissue, implants, severe dysplastic disease, or significant architectural distortion following breast surgery or radiation therapy. Different noninvasive imaging techniques have been evaluated to overcome these limitations. Nuclear medicine also has been actively involved in the detection of breast cancer, using various types of radiopharmaceuticals. Currently, there are three radiotracers commonly used for breast imaging or scintimammography in either clinical practice or research: 99mTc-sestamibi and 99mTc-tetrofosmin (two agents used for myocardial perfusion imaging) and 99mTc MDP (methylene diphosphonate, used for bone scintigraphy). 99mTc-sestamibi was the first radiopharmaceutical to be approved by the FDA for scintimammography. Several prospective studies have shown that the overall sensitivity of 99mTc sestamibi scintimammography in detection of breast cancer was 85%, the specificity was 89%, and the positive and negative predictive values were 89% and 84% respectively. Similar numbers have been demonstrated for 99mTc-tetrofosmin and 99mTc-MDP scintimammography. Although not indicated as a screening procedure for the detection of breast cancer, scintimammography may play a useful and significant role in various specific clinical indications such as nondiagnostic or difficult mammography, and evaluation of high-risk patients, tumor response to chemotherapy, and axillary lymph node metastatic involvement. PMID- 9990682 TI - Breast cancer imaging with radiolabeled antibodies. AB - Over the past 2 decades, numerous anticancer antibodies against different molecular targets and labeled with different gamma-emitting radionuclides have been studied in human tumor xenografts and in clinical trials. In breast cancer, these molecular targets have included principally tumor-associated antigens, such as carcinoembryonic antigen (CEA) and the polymorphic epithelial mucin antigen, MUC1, and more recently the growth factor receptors, EGF-R and HER-2/neu. No antibody-based agent has yet been approved for clinical use in the diagnosis of mammary carcinoma, because few trials have addressed the issue of clinical use of these imaging agents in the management of breast cancer patients. Recently, the CEA antibody Fab' fragment approved for colorectal cancer detection, Arcitumomab (CEA-Scan, [Immunomedics, Morris Plains, NJ]), has been found to image both palpable and nonpalpable breast lesions that were suspicious on screening mammograms. Results to date indicate that Arcitumomab can complement mammography by providing a high specificity and positive predictive value, thus indicating when a patient with an abnormal mammogram may proceed directly to definitive surgery without an intermediate diagnostic biopsy. Breast cancer immunoscintigraphy holds promise for advancing toward immunoPET, which should combine the specificity of antibodies with the high sensitivity and resolution of PET. It is also the foundation of breast cancer radioimmunotherapy with humanized antibodies against CEA and MUC1, as well as other immunotherapy strategies. PMID- 9990683 TI - 18-FDG imaging in breast cancer. AB - Despite the large number of women with breast cancer and the importance of this disease in health care, only a relatively small number of published reports involve the application of 18-fluorodeoxyglucose (FDG) in the evaluation of patients with breast cancer. This report summarizes the results of these studies, presents the opinions from various clinical oncologists from both a university and community setting, and discusses the possible future implication of positron imaging technology in the management of breast cancer. The four potential areas of clinical application include (1) detection and differentiation of primary breast lesions, (2) staging of axillary lymph nodes, (3) detection of residual and metastatic disease, and (4) monitoring the response to chemotherapy. PMID- 9990684 TI - Sentinel node localization in breast cancer. AB - The status of the axillary nodes is the strongest known prognostic variable in patients with early breast cancer, and is routinely used in planning postoperative therapy. Conventional axillary lymph node dissection is limited by sampling error and potential morbidity. Sentinel node techniques have revolutionized the management of axillary nodes. Accurate identification and focused histologic evaluation of the sentinel node allow accurate prediction of the tumor status of other axillary nodes, thereby avoiding the morbidity and expense of a complete axillary dissection in node-negative patients. Radiotracer techniques play an important role in the preoperative and intraoperative localization of the sentinel nodes. Optimal localization of the sentinel node requires the use of both preoperative lymphoscintigraphy and intraoperative radiosensitive probes. Lymphoscintigraphy also identifies patients with lymphatic drainage to sites other than the axilla, thereby allowing more appropriate treatment and follow-up in this subset of patients. Procedures for localizing sentinel nodes require an understanding of the kinetics of the radiopharmaceuticals or other tracers used and the detection devices employed in each institution. Both surgical and nuclear medicine personnel should understand these principles, and close cooperation between surgeons, nuclear medicine physicians, and pathologists is essential for the application of sentinel node techniques. PMID- 9990685 TI - Skeletal metastases from breast cancer: imaging with nuclear medicine. AB - Breast cancer is a disease that commonly metastasizes to bone, increasing morbidity, mortality, and health service costs. The 99m technetium (99mTc) diphosphonate bone scan historically has played a significant part in the evaluation of skeletal disease and continues to be one of the most clinically utilized investigations in the staging and follow up of breast cancer patients. More tumor-specific radiopharmaceuticals are now being evaluated and, in particular, 18-fluoro-2-deoxyglucose positron emission tomography (18FDG PET) may have a greater role in this disease in the future. PMID- 9990686 TI - Intestinal accumulation of Tc 99m MDP on bone scan. PMID- 9990687 TI - Nonvisualization of gallbladder after endoscopic retrograde sphincterotomy. PMID- 9990688 TI - Heterogenous uptake on brain SPECT. PMID- 9990689 TI - A unified approach to the analysis of case-distribution (case-only) studies. AB - A number of new study designs have appeared in which the exposure distribution of a case series is compared to an exposure distribution representing a complete theoretical population or distribution. These designs include the case-genotype study, the case-cross-over study, and the case-specular study. This paper describes a unified likelihood-based approach to the analysis of such studies, and discusses extensions of these methods when a control group is available. The approach clarifies certain assumptions implicit in the methods, and helps contrast these assumptions to those underlying ordinary case-control studies. There are several reasons to expect discrepancies between ordinary case-control estimates and case-distribution estimates; for example, case-distribution estimates can be more sensitive to exposure misclassification. Some discrepancies are illustrated in an application to case-specular data on wire codes and childhood cancer. PMID- 9990690 TI - Describing time and age variations in the risk of radiation-induced solid tumour incidence in the Japanese atomic bomb survivors using generalized relative and absolute risk models. AB - Generalized relative and absolute risk models, in which various functions of time and age modify the excess relative or absolute risk of radiation-induced cancer, are fitted to the Japanese atomic bomb survivor cancer incidence data set. Among generalized relative risk models, those in which a product of powers of time since exposure and attained age modify the relative risk provide the best fit. There are indications that the Armitage-Doll model (in its formulation as a generalized relative risk model) provides a poor fit to the data, possibly in part because of increasing age-adjusted cancer incidence rates in the Japanese cohort. Generalized absolute risk models, and in particular models in which either powers of time since exposure and attained age, or powers of time since exposure and age at exposure modify the excess absolute risk, provide a superior fit to any of the generalized relative risk models for all solid cancer sites analysed together. When six cancer subtypes are examined separately, only for respiratory cancers does this finding remain true, and for two other sites (female breast cancer and thyroid cancer) the generalized relative risk model yields a better fit than the generalized absolute risk model. PMID- 9990691 TI - Classifying individuals based on predictors of random effects. Multicenter AIDS Cohort Study. AB - Often one wishes to describe individuals according to whether their average exposure over a period of time is above or below some meaningful threshold. In this article, we treat predictors of random effects as diagnostic tools to aid in such classification, given that the true unobservable mean exposure for each of a set of individuals is defined according to a mixed linear model. Viewing candidate predictors in this light engenders the consideration of a unique set of performance criteria, and invites the use of nomenclature commonly used by epidemiologists and decision analysts to evaluate diagnostic techniques. We describe these criteria analytically and graphically under a random effects analysis of variance model, with the expressed goal of classifying subjects with regard to their true mean. Given knowledge of the model parameters, we compare typical predictors and illustrate the fact that completely new alternatives can arise depending on the particular set of criteria emphasized. We include a brief simulation study in which we also compare prediction methods according to various classification criteria, after incorporating estimates of the unknown model parameters. We provide two examples using data from participants in the Multicenter AIDS Cohort Study. In the first example, we seek to classify HIV seronegative individuals based on their mean diastolic blood pressure. In the second, via a natural extension to a randomized regression model, we classify HIV seropositive individuals according to their CD4+ slope over time. PMID- 9990692 TI - A Markov model for measuring vaccine efficacy for both susceptibility to infection and reduction in infectiousness for prophylactic HIV vaccines. AB - We use a discrete-time non-homogeneous Markov chain to model data from augmented human immunodeficiency virus (HIV) vaccine trials. For this design, the study population consists of primary participants some of whom have steady sexual partners who are also enrolled to augment the trial. The state space consists of the infection status of primary participants without steady partners and the infection status of both persons in the steady partnerships. The transition probabilities are functions of the two parameters: vaccine efficacy for susceptibility (VES) and infectiousness (VEI). We use likelihood methods to estimate VES and VEI from time-to-event data. We then use stochastic simulations to explore the bias and precision of the estimators under various plausible conditions for HIV vaccine trials. We show that both the VES and VEI are estimable with reasonable precision for the conditions that may exist for planned HIV vaccine trials. We show that exams conducted every six months will likely provide sufficient information to estimate the VE parameters accurately, and that there is little gain in precision for more frequent exams. Finally, we show that joint estimation of the VES and VEI will likely be feasible in a currently planned HIV vaccine trial among injecting drug users in Bangkok, Thailand, if one augments the information about the primary participants in the trial with information about their steady sexual partners. PMID- 9990693 TI - Monitoring paired binary surgical outcomes using cumulative sum charts. AB - Correlated binary data are encountered in many areas of medical research, system reliability and quality control. For monitoring failures rates in such situations, simultaneous bivariate cumulative sum (CUSUM) charts with the addition of secondary control limits are proposed. Using an approach based on a Markov chain model, the run length properties of such a monitoring scheme can be determined for sudden, or gradual, changes in the failure rates. The proposed control charts are easy to implement, and are shown to be very effective at detecting small changes in the rate of undesirable outcomes, especially when the changes are gradual. This procedure is illustrated using bivariate outcome data arising from a series of paediatric surgeries. The methodology is sufficiently general that it may be adapted for multivariate normal, binomial or Poisson responses. PMID- 9990694 TI - Sample size formula with a continuous outcome for unequal group sizes and unequal variances. AB - Guenther derived a simple formula for the accurate computation of equal sample sizes when the two-sample t-test with pooled variance estimate is used. In the present paper, the Guenther formula is generalized to the case of unequal sample sizes. In addition, the case of unequal variances is considered. PMID- 9990695 TI - Sample size determination for proving equivalence based on the ratio of two means for normally distributed data. AB - Equivalence trials aim to demonstrate that two treatments do not differ by more than a prespecified clinically irrelevant amount. We consider the problem when equivalence is defined in terms of the ratio of population means and the original (untransformed) data are normally distributed. Application of the intersection union principle to the test proposed by Sasabuchi results in a two one-sided tests procedure of size alpha. We give the associated 100 (1-2 alpha) per cent confidence interval and derive the exact methods for calculation of power and sample sizes for the parallel group design and the two-period cross-over. We present tables and figures of required sample sizes and achieved power. PMID- 9990696 TI - Estimating the proportion of treatment effect explained by a surrogate marker. PMID- 9990697 TI - Confidence intervals for differences in correlated binary proportions. PMID- 9990698 TI - Investigating underlying risk as a source of heterogeneity in meta-analysis. PMID- 9990699 TI - Of oxymorons and ostriches. PMID- 9990700 TI - Electromyography in the horse in veterinary medicine and in veterinary research- a review. AB - In veterinary practice electromyography is a useful diagnostic technique for differentiating neuropathies, junctionopathies, and myopathies. The electromyogram gives information on the state of activity of motor neurons at rest, in reflex contraction, and in voluntary contraction. As a research tool, the electromyogram can be used to understand the complexity of the neuromuscular system. It has applications in horses for assessing muscle activation patterns and for providing a more complete understanding of the pathology of the muscles and nerves. PMID- 9990701 TI - Nortestosterone is not a naturally occurring compound in male cattle. AB - Nortestosterone (beta-NT) is a hormonal growth promoter banned from livestock production in the EU. Following injection, the major metabolite in cattle is the 17 alpha-epimer (alpha-NT). However, this also occurs naturally in pregnant cattle. It is not known whether alpha-NT is also endogenous to intact or castrated male cattle. Three surveys were undertaken to assess whether alpha-NT is naturally produced in this subset of the population. Bile samples from a total of 1,281 cattle (73 bulls and 1,208 steers) from 366 herds were collected at slaughter and initially screened by using a semi-automated EIA with multi-analyte immunoaffinity chromatography (IAC) clean-up. Bile samples from a further 38 male cattle (10 bulls and 28 steers) were analysed by high-resolution gas chromatography-mass spectrometry (GC-MS) with IAC pretreatment. Only samples containing more than 2 ng/ml alpha-NT were subjected to GC-MS. With 2 ng/ml alpha NT as a threshold for confirmatory testing, the false positive rate of the screening EIA was 1.8%. Bulls (n = 16) and steers (n = 179) from government farms (n = 2) and which were not treated with exogenous beta-NT, did not have measurable concentrations of alpha-NT in their bile. Bulls (n = 35) and steers (n = 606) taken from herds (n = 204) which had no previous history of illegal growth promoter abuse also did not have alpha-NT in their bile. Of 32 bulls and 451 steers of unknown treatment history sampled from herds (n = 160), 56 steers from 19 herds contained GC-MS confirmed concentrations of alpha-NT higher than the limit of quantification of the assay LOQ (0.7 ng/ml). Of these animals, two had beta-NT-containing injection sites and five had residues of the beta-agonists clenbuterol and mabuterol. Examination of the animal movement and ownership histories of the 56 confirmed positive animals strongly suggested that exogenous beta-NT had been administered at the presenting farm. It is concluded that alpha NT is not endogenous to this subset of the cattle population and that detection of this hormone in bile from bulls and steers constitutes evidence of abuse. PMID- 9990702 TI - A serological study of cohorts of young dogs, naturally exposed to Ixodes ricinus ticks, indicates seasonal reinfection by Borrelia burgdorferi sensu lato. AB - Thirty-three family dogs were monitored for antibodies to Borrelia burgdorferi sensu lato over a 3-year period. Serum samples were collected before and during the season of high tick activity. Antibody levels were measured with an ELISA based on whole-cell antigens and an ELISA with a purified recombinant flagellin (r410). Antibody levels measured with the whole-cell ELISA increased after the first exposure to ticks. Following the first seasonal period of tick quiescence, antibody levels decreased, and subsequently increased again in the second tick season. Thereafter whole-cell ELISA titres persisted at moderate levels and did not decrease between tick seasons. The recombinant flagellin ELISA did not show a strong response in the first tick season, but did in the second tick season and levels of antibodies continued to fluctuate thereafter. We conclude that most dogs in this study developed an antibody response against Borrelia burgdorferi sensu lato after their first tick infestation and were thereafter repeatedly immunologically stimulated, probably reinfected, during the consecutive tick seasons. PMID- 9990703 TI - Suitability of the Charm HVS and a microbiological multiplate system for detection of residues in raw milk at EU maximum residue levels. AB - In this paper we assessed the suitability of the Charm HVS and a newly developed microbiological multiplate system as post-screening tests to confirm the presence of residues in raw milk at or near the maximum permissible residue level (MRL). The multiplate system is composed of Bacillus stearothermophilus var. calidolactis plate at pH 8.0 for detection of beta-lactam antibiotics and tylosin, Bacillus cereus plate at pH 6.0 for detection of tetracyclines, Micrococcus luteus plate at pH 8.0 for detection of macrolides, Bacillus subtilis BGA plate at pH 8.0 for detection of aminoglycosides, trimethoprim-containing plate seeded with B. subtilis BGA at pH 7.0 for detection of sulphonamides, Escherichia coli plate at pH 6.0 for detection of quinolone and polymyxin, and Staphylococcus epidermidis plate at pH 6.0 for detection of novobiocin. For each test plate an action level is proposed in such a way that residues can be detected in raw bulk tank milk at levels near or below the established EU MRLs of beta-lactam antibiotics, tetracyclines, aminoglycosides, macrolides, sulphonamides, colistin, and quinolones. The Charm HVS test used to confirm the presence of tetracycline and macrolide residues gave false-positive results near the EU MRLs. The multiplate system gave valid results. Based on data for raw bulk tank milk samples and the proposed action level for each test plate for suspected samples, we demonstrated that the multiplate system is a reliable post-screening method that can be performed easily and cheaply in microbiological laboratories. PMID- 9990704 TI - Prevalence of bovine virus diarrhoea virus infection in Belgian white blue cattle in southern Belgium. AB - A study was conducted in Southern Belgium to determine the prevalence of bovine viral diarrhoea virus (BVDV) infection in Belgian White Blue herds. Blood samples were taken from 9685 cattle, representing all the stock on 61 farms, by local veterinarians to screen for persistently infected animals and to determine their serological status against BVDV. Some of the herds (42.5%) were selected because of a prior positive diagnosis of BVDV or on the grounds of suspicion of BVD. A capture enzyme-linked immunosorbent assay (ELISA) was used to test for antigen. The prevalence of persistently infected animals was 0.75% overall and 1.46% in the 27 herds with at least one persistently infected animal. The prevalence of seropositive animals was determined with a competitive antibody ELISA and was found to be 65.5% for the animals as a whole but 53.8% for the herds without positively infected animals and 76.6% for the herds with at least one such animal. All the herds contained seropositive animals. PMID- 9990705 TI - Treatment of cystic ovarian disease in dairy cows with gonadotrophin-releasing hormone: a field study. AB - In a field trial in the Netherlands 765 dairy cows were treated during 869 lactations with 500 micrograms gonadotrophin-releasing hormone (gonadorelin i.m.) for cystic ovarian disease (COD) between June 1987 and April 1996. COD was defined as the presence of a large follicle (> 2.5 cm) on one or both of the ovaries in the absence of a corpus luteum. Two treatment groups were formed, based on the interval from parturition to first treatment, with day 60 being the cut-off between groups 1 and 2. The aim of this study is to examine whether there is a relationship between the moment of diagnosis and treatment (before or after day 60 post partum) and its result. In group 1 90.0% of first treatments were effective and in group 2 93.3% (p = 0.08). This was reflected by the slightly higher number of treatments needed for animals in group 1 (1.11 versus 1.07, p = 0.08). The efficacy rate after one treatment did not significantly differ between the groups (1.63 versus 1.69, p = 0.40) and nor did the interval between 1st insemination after treatment and conception (p < 0.63). In conclusion, it can be stated that gonadorelin is effective as therapy irrespective of the timing of diagnosis and treatment. PMID- 9990707 TI - Characteristics of gene 28 product, the constituent of the central part of bacteriophage T4 baseplate. AB - The phage TD gene 28 product has been partially characterized and its biological role has been examined. It was found to be a protein with a molecular size of 24 kDa which cosediments with the membrane fraction of the bacterial extracts and could only be washed out by a 0.2% sarcosyl solution. Other observations indicate that gp 28 has a majority of hydrophobic residues on its surface and forms a homotrimeric complex in the absence of other phage proteins. The product was finally identified as a baseplate structural component. Incubation of purified phage preparation in a buffer which contained active protein 28, did not affect the efficiency of the plating. However, incubation of the phage particles with specific antiserum was found to neutralize phage infectivity. PMID- 9990708 TI - Effect of chemical nutrients on aconitase activity during citric acid fermentation by a mutant strain of Aspergillus niger. AB - An ethyleneimine and UV irradiated mutant strain Aspergillus niger AB 1801 was explored for its aconitase activity, citric acid production and cell growth during citric acid fermentation. 10% sucrose and 0.25% urea served as the best carbon and nitrogen sources, respectively. Fe2+ stimulated aconitase activity and Co2+ (upto 5 micrograms/mL) and Ni2+ (10 micrograms/mL) strongly depressed enzyme activity. Boric acid (0.5 mg/L) had very good stimulatory response towards citric acid production. Aconitase activity has been found to vary inversely with the citric acid production upto a certain limit after which the activity was absent in the mycelial extract. Cell growth varied with the production parameter. PMID- 9990709 TI - Antiviral activity of 1,7-disulphoanthraquinone. AB - The antiviral activity of 1,7-disulphoanthraquinone (DSA) against hepatitis B viruses was investigated by measuring the titer of HBV surface antigen in the treated serum obtained from the blood of patients with acute infection. The presence of HBsAg was tested by the Vitek Immuno Diagnostic Assay System (VIDAS). The concentration of DSA in the samples was equal to 0.01, 0.1 and 1%, respectively. The results presented clearly showed an extensive disintegration of the virus envelope at elevated temperatures, which resulted in a substantial decrease in the concentration of HBsAg in the serum containing DSA. The concentration of HBsAg decreased also upon UV irradiation of the serum containing DSA in a photochemical reactor for 5 to 15 min, but the effect of degradation was not complete. PMID- 9990710 TI - Prevalence of high level aminoglycoside and vancomycin resistance among enterococci in Turkey. AB - Enterococcus spp. have become the third most common cause of nosocomial infections. High-level aminoglycoside resistance (HLAR), an important clinical concern, has been associated with some species of enterococci. The synergistic effect obtained by the combination of aminoglycosides with penicillin or vancomycin disappears in strains that show high-level resistance (HLR) to the aminoglycosides. We evaluated the agar dilution and high content disk diffusion tests for the detection of HLAR for 60 isolated enterococci. In our study 4 strains of Enterococcus faecalis (6.6%) and 8 strains of Enterococcus faecium (13.3%), totally 20% were found to be highly resistant to gentamicin; 2 strains of E. faecalis (13.3%), 8 strains of E. faecium (3.3%), totally 16.6% showed HLR to streptomycin by agar dilution method and the same rates were found by high content disk diffusion method. 2 strains of E. faecalis (3.3%), 4 strains of E. faecium (6.6%), totally 10% showed vancomycin resistance by agar dilution method. The ratio for beta lactamase activity was found to be 26.6% for E. faecalis and 3.3% for E. faecium. Our results demonstrate that high-content disk diffusion test should be performed by using both gentamicin and streptomycin in routine screening of HLAR among enterococci and the determination of beta lactamase activity at the same time is also useful for detecting resistance to a beta lactam agent. PMID- 9990711 TI - The susceptibility of gram-negative rods and their adaptive forms resistant to colistine to the bactericidal action of sera. AB - The susceptibility of Escherichia coli K1, Salmonella enteritidis, Salmonella typhimurium strains and their adaptative forms resistant to colistine (Colr forms) was compared with respect to their sensitivity to the bactericidal action of normal cord serum and normal bovine serum. It has been shown that the Colr forms are more susceptible to sera as compared to initial strains. The increase of sensitivity of the Colr forms is connected with structural changes within bacterial cell wall which is the target for complement as well as for colistine. PMID- 9990712 TI - Adaptation of a phenol-degrading denitrifying bacteria to high concentration of phenol in the medium. AB - The growth and uptake of phenol by 8 strains isolated from wastewater sediments in stationary cultures in medium with increasing concentrations of phenol (from 100 to 600 mg/L) under denitrifying conditions were studied. All the strains grew in media containing 250 mg phenol/L and only strains 101/1, 83/2 and 21/1/ in consecutive passages visibly increased both specific growth rate (mu day-1) as well as phenol-degrading activity (mg/L x day). Consecutive passages of the culture in medium containing 400 mg phenol/L resulted in the elimination of 3 out of the 5 strains growing in the medium in the first passage. Only strain 101/1 demonstrated high specific growth rate and phenol-degrading activity in medium containing 600 mg phenol/L. In consecutive passages in medium containing 250, 400 and 600 mg phenol/L the specific growth (mu day-1) and phenol-degrading activity (mg/L x day) of P. aeruginosa 101/1 were 0.38 and 36; 0.12 and 19; 0.09 and 20, respectively. PMID- 9990713 TI - An attempt to use selected strains of bacteria adapted to high concentrations of petroleum oil to increase the effective removal of petroleum products in excess activated sludge in laboratory conditions. AB - Forty two strains of bacteria were isolated from excess activated sludge from petroleum wastewater treatment plant. The strains were identified and classified to the following groups: Enterobacteriaceae (7 strains), Anitratum (3 strains), Pseudomonas (13 strains), Micrococcus (12 strains), Comamonas (2 strains), Xanthomonas (2 strains), Achromobacter (1 strain) and Vibrio-Aeromonas (1 strain). One of the isolates was found to be a yeast strain. Following preliminary selection ten strains, showing the best growth in medium with oil fraction as sole carbon source, were chosen for further studies. The selected strains belong to Pseudomonas (6 strains), Xanthomonas (2 strains), Micrococcus (1 strain) and Saccharomyces (1 strain). The strains were adapted to high oil concentration (500-2000 mg/L) and an attempt to use them to intensify removal of petroleum products from excess activated sludge was made. The sludge was inoculated with a mixture of the isolated strains. The experiment was carried out three times, each time with a fresh sample of the excess sludge. The obtained results show that the inoculation of activated sludge with the strains active against oil reduced the petroleum products content by 20% in 14 days. The greatest reduction of oil was observed in sludge with the lowest dry weight, that is with the greatest degree of hydration. The dry weight of the excess sludge did not significantly decrease during the course of the experiment, after having been inoculated with the mixture of strains. PMID- 9990714 TI - Genomic fingerprinting of Proteus species using repetitive sequence based PCR (rep-PCR). AB - Three Proteus species P. vulgaris, P. mirabilis and P. penneri have been characterized by repetitive sequence-based PCR. Four families of repetitive sequence based primers REP, ERIC, BOXA1R and BOXA2R, give specific patterns for each Proteus species. Species differentiation was best afforded using BOXA2R for detection of P. mirabilis, either REP-Dt or BOXA1R primers for detection of P. penneri and ERIC primer pair for P. vulgaris. PMID- 9990715 TI - Insects as food: why the western attitude is important. AB - The traditional use of insects as food continues to be widespread in tropical and subtropical countries and to provide significant nutritional, economic and ecological benefits for rural communities. Westerners should become more aware of the fact that their bias against insects as food has an adverse impact, resulting in a gradual reduction in the use of insects without replacement of lost nutrition and other benefits. PMID- 9990716 TI - Emerging and resurging vector-borne diseases. AB - Over the last four decades, a number of arthropod-borne infections have been recognized for the first time. Some have become of considerable public health importance, such as dengue hemorrhagic fever (DHF), and others are spreading geographically and their incidence is increasing. There has been an important recrudescence of several long-known vector-borne diseases. Malaria, leishmaniasis, dengue, and plague have resurged in numerous foci, in some cases where they were thought to be under effective control. In most instances, the appearance of new diseases and syndromes and the resurgence of old can be associated with ecological changes that have favored increased vector densities. Dam construction, irrigation and other development projects, urbanization, and deforestation have all resulted in changes in vector population densities that appear to have enabled the emergence of new diseases and the resurgence of old diseases. Greatly increased human travel has spread infectious agents, introducing them into areas in which they had been hitherto absent. It is essential to understand the factors that caused increased vector densities and hence the transmission of disease to prevent the emergence and resurgence of more diseases, as well as to serve as a basis for effective control. PMID- 9990717 TI - The evolution and development of dipteran wing veins: a systematic approach. AB - In this review, we use the wing veins of dipteran insects as potential models for understanding the evolution of development. We briefly discuss previous work in this field and examine the genetic complexity of wing formation, discussing the genes involved in wing formation and their roles in Drosophila wing development and vein formation. Furthermore, patterns of wing vein formation, addition, and reduction are discussed as they occur throughout the Diptera. Using the phyletic phenocopy paradigm, we draw attention to many wing vein morphologies that phenocopy various wing mutants in Drosophila melanogaster. The systematic issues of the nature of characters, homology, and the role of modern developmental approaches to evolutionary studies, which has recently become important, can be addressed from the perspective of the wing. We argue that further developmental evolutionary studies, and the interpretation of data therefrom, must be conducted within the context of a well-supported phylogeny of the organisms under study. PMID- 9990718 TI - Odor-mediated behavior of Afrotropical malaria mosquitoes. AB - The African mosquito species Anopheles gambiae sensu lato s.l. and Anopheles funestus rank among the world's most efficient vectors of human malaria. Their unique bionomics, particularly their anthropophilic, endophagic and endophilic characters, guarantee a strong mosquito-host interaction, favorable to malaria transmission. Olfactory cues govern the various behaviors of female mosquitoes and here we review the role of semiochemicals in the life history of African malaria vectors. Recent evidence points towards the existence of human-specific kairomones affecting host-seeking A. gambiae s.l., and efforts are under way to identify the volatiles mediating this behavior. Based on examples from other Culicidae spp., it is argued that there is good reason to assume that mating, sugar feeding, and oviposition behavior in Afrotropical malaria vectors may also be mediated by semiochemicals. It is foreseen that increased knowledge of odor mediated behaviors will be applied in the development of novel sampling techniques and possibly alternative methods of intervention to control malaria. PMID- 9990719 TI - Pathogens and predators of ticks and their potential in biological control. AB - This review summarizes the literature about pathogens and predators of ticks and their potential use as biocontrol agents published since the beginning of this century. In nature, many bacteria, fungi, spiders, ants, beetles, rodents, birds, and other living things contribute significantly toward limiting tick populations, as do, for instance, the grooming activities of hosts. Experiments with the most promising potential tick biocontrol agents--especially fungi of the genera Beauveria and Metarhizium and nematodes in the families Steinernematidae and Heterorhabditidae, as well as oxpeckers--are described. PMID- 9990720 TI - Recent advances in cassava pest management. AB - Cassava (Manihot esculenta) occupies a uniquely important position as a food security crop for smallholder farmers in ares of the tropics where climate, soils, or societal stresses constrain production. Given its reliability and productivity, cassava is the most important locally produced food in a third of the world's low-income, food-deficit countries. It is the fourth most important source of carbohydrates for human consumption in the tropics, after rice, sugar, and maize. World production of cassava from 1994-1996 averaged 166 million tons/year grown on 16.6 million hectares (ha), for an average yield of 9.9 tons/ha. Approximately 57% is used for human consumption, 32% for animal feed and industrial purposes, and 11% is waste. Africa accounts for 51.3% of the production; Asia, 29.4%; and Latin America, 19.3%. The area planted to cassava in Africa, Asia, and Latin America is 10.3, 3.7, and 2.6 million ha, respectively. PMID- 9990721 TI - The insect voltage-gated sodium channel as target of insecticides. AB - Examination of the function, chemistry, and pharmacology of the voltage-gated insect sodium channel (ISC) reveals that the ISC closely resembles its vertebrate counterpart in electrophysiology and ion conductance, primary structure and allocation of all functional domains, and its pharmacological diversity and flexibility exhibited by the occurrence of different allosterically coupled receptor-binding sites for various neurotoxicants. The toxicants include several groups of insecticides, namely DDT and its analogues, pyrethroids, N-alkylamides, and dihydropyrazoles, which affect channel gating and ion permeability. Despite their similarity, the insect and vertebrate channels are pharmacologically distinguishable, as revealed by the responsiveness of the heterologously expressed Drosophila para clone to channel modifiers and blockers and the occurrence of the insect-selective sodium channel neurotoxins derived from arachnid venoms presently used for the design of recombinant baculovirus-mediated selective bioinsecticides. The pharmacological specificity of the ISC may lead to the design of insect-selective toxicants, and its pharmacological flexibility may direct the use of ISC insecticides for resistance management. Insecticide resistance [such as knockdown resistance (KDR)] is acquired by natural selection and operated by increased metabolism, channel mutagenesis, or both. The resistance issue can be dealt with in several ways. One is by simultaneous application of low doses of synergistic, allosterically coupled mixtures (thus delaying or preventing the onset of resistance). An alternative is to replace an insecticide to which resistance was acquired by channel mutation with a different ISC toxicant to which increased susceptibility was conferred by the same mutation. Such a possibility was exemplified by a significant increase in susceptibility to N-alkylamides, as well as an insect-selective neurotoxin revealed by KDR insects. Third, both of these methods can be combined. Thus owing to its pharmacological uniqueness, the ISC may serve as a high-priority target for future selective and resistance-manageable insecticides. PMID- 9990722 TI - Insect P450 enzymes. AB - The P450 enzymes (mixed function oxidases, cytochrome P450 monooxygenases), a diverse class of enzymes found in virtually all insect tissues, fulfill many important tasks, from the synthesis and degradation of ecdysteroids and juvenile hormones to the metabolism of foreign chemicals of natural or synthetic origin. This diversity in function is achieved by a diversity in structure, as insect genomes probably carry about 100 P450 genes, sometimes arranged in clusters, and each coding for a different P450 enzyme. Both microsomal and mitochondrial P450s are present in insects and are best studied by heterologous expression of their cDNA and reconstitution of purified enzymes. P450 genes are under complex regulation, with induction playing a central role in the adaptation to plant chemicals and regulatory mutations playing a central role in insecticide resistance. Polymorphisms in induction or constitutive expression allow insects to scan their P450 gene repertoire for the appropriate response to chemical insults, and these evolutionary pressures in turn maintain P450 diversity. PMID- 9990723 TI - Oxygen sensing by the global regulator, FNR: the role of the iron-sulfur cluster. AB - FNR is a global regulator that controls transcription of genes whose functions facilitate adaptation to growth under O2 limiting conditions. It has long been appreciated that the activity of FNR must be regulated by O2 availability, since FNR dependent gene expression is observed in vivo only under anaerobic conditions, while similar levels of this protein are present in both aerobic and anaerobic grown cells. Recent progress in this field has shown that anaerobically purified FNR contains a [4Fe-4S]2+ cluster and that this [4Fe-4S]2+ cluster is sufficiently unstable toward O2 to make it suitable as an O2 sensor. The presence of the [4Fe-4S] cluster increases dimerization of FNR which is correlated with an increase in site-specific DNA binding of FNR, a property expected of transcription factors of the FNR/CRP family. According to Mossbauer spectroscopy on purified FNR and cells containing overexpressed FNR, the [4Fe-4S]2+ cluster of FNR is converted by O2 to a [2Fe-2S]2+ in high yield. The [2Fe-2S]2+ cluster can be reconverted to the [4Fe-4S]2+ cluster on reduction with dithionite in vitro raising the possibility that the [2Fe-2S]2+ cluster is a biologically inactive intermediate which may be more readily available for reconstitution into the [4Fe 4S]2+ form than the Fe-free apoform. The ability to observe, by Mossbauer spectroscopy, the Fe-S clusters of FNR in cells containing high levels of FNR should be of value in further unraveling how FNR functions in vivo. Attempts to reduce the [4Fe-4S]2+ cluster of FNR with dithionite indicated that the redox potential of the +1/+2 couple is < or = -650 mV and that the [4Fe-4S]+ cluster form is, therefore, not likely to occur in vivo. PMID- 9990724 TI - Microbial desulfonation. AB - Organosulfonates are widespread compounds, be they natural products of low or high molecular weight, or xenobiotics. Many commonly found compounds are subject to desulfonation, even if it is not certain whether all the corresponding enzymes are widely expressed in nature. Sulfonates require transport systems to cross the cell membrane, but few physiological data and no biochemical data on this topic are available, though the sequences of some of the appropriate genes are known. Desulfonative enzymes in aerobic bacteria are generally regulated by induction, if the sulfonate is serving as a carbon and energy source, or by a global network for sulfur scavenging (sulfate-starvation-induced (SSI) stimulon) if the sulfonate is serving as a source of sulfur. It is unclear whether an SSI regulation is found in anaerobes. The anaerobic bacteria examined can express the degradative enzymes constitutively, if the sulfonate is being utilized as a carbon source, but enzyme induction has also been observed. At least three general mechanisms of desulfonation are recognisable or postulated in the aerobic catabolism of sulfonates: (1) activate the carbon neighboring the C-SO3- bond and release of sulfite assisted by a thiamine pyrophosphate cofactor; (2) destabilize the C-SO3- bond by addition of an oxygen atom to the same carbon, usually directly by oxygenation, and loss of the good leaving group, sulfite; (3) an unidentified, formally reductive reaction. Under SSIS control, different variants of mechanism (2) can be seen. Catabolism of sulfonates by anaerobes was discovered recently, and the degradation of taurine involves mechanism (1). When anaerobes assimilate sulfonate sulfur, there is one common, unknown mechanism to desulfonate the inert aromatic compounds and another to desulfonate inert aliphatic compounds; taurine seems to be desulfonated by mechanism (1). PMID- 9990725 TI - The anaerobic oxidation of ammonium. AB - From recent research it has become clear that at least two different possibilities for anaerobic ammonium oxidation exist in nature. 'Aerobic' ammonium oxidizers like Nitrosomonas eutropha were observed to reduce nitrite or nitrogen dioxide with hydroxylamine or ammonium as electron donor under anoxic conditions. The maximum rate for anaerobic ammonium oxidation was about 2 nmol NH4+ min-1 (mg protein)-1 using nitrogen dioxide as electron acceptor. This reaction, which may involve NO as an intermediate, is thought to generate energy sufficient for survival under anoxic conditions, but not for growth. A novel obligately anaerobic ammonium oxidation (Anammox) process was recently discovered in a denitrifying pilot plant reactor. From this system, a highly enriched microbial community with one dominating peculiar autotrophic organism was obtained. With nitrite as electron acceptor a maximum specific oxidation rate of 55 nmol NH4+ min-1 (mg protein)-1 was determined. Although this reaction is 25 fold faster than in Nitrosomonas, it allowed growth at a rate of only 0.003 h-1 (doubling time 11 days). 15N labeling studies showed that hydroxylamine and hydrazine were important intermediates in this new process. A novel type of hydroxylamine oxidoreductase containing an unusual P468 cytochrome has been purified from the Anammox culture. Microsensor studies have shown that at the oxic/anoxic interface of many ecosystems nitrite and ammonia occur in the absence of oxygen. In addition, the number of reports on unaccounted high nitrogen losses in wastewater treatment is gradually increasing, indicating that anaerobic ammonium oxidation may be more widespread than previously assumed. The recently developed nitrification systems in which oxidation of nitrite to nitrate is prevented form an ideal partner for the Anammox process. The combination of these partial nitrification and Anammox processes remains a challenge for future application in the removal of ammonium from wastewater with high ammonium concentrations. PMID- 9990726 TI - Biotransformation of monoterpenes, bile acids, and other isoprenoids in anaerobic ecosystems. AB - Isoprenoic compounds play a major part in the global carbon cycle. Biosynthesis and mineralization by aerobic bacteria have been intensively studied. This review describes our knowledge on the anaerobic metabolism of isoprenoids, mainly by denitrifying and fermentative bacteria. Nitrate-reducing beta-Proteobacteria were isolated on monoterpenes as sole carbon source and electron donor. Thauera spp. were obtained on the oxygen-containing monoterpenes linalool, menthol, and eucalyptol. Several strains of Alcaligenes defragrans were isolated on unsaturated monoterpenes as growth substrates. A novel denitrifying beta Proteobacterium, strain 72Chol, mineralizes cholesterol completely to carbon dioxide. Physiological studies showed the presence of several oxidative pathways in these microorganisms. Investigations by organic geochemists indicate possible contributions of anaerobes to early diagenetic processes. One example, the formation of p-cymene from monoterpenes, could indeed be detected in methanogenic enrichment cultures. In man, cholic acid (CA) and chenodeoxycholic acid (CDCA), are synthesized in the liver from cholesterol. During their enterohepatic circulation, bile acids are biotransformed by the intestinal microflora into a variety of metabolites. Known bacterial biotranformations of conjugated bile acids include: deconjugation, oxidation of hydroxy groups at C-3, C-7 and C-12 with formation of oxo bile acids and reduction of these oxo groups to either alpha- or beta-configuration. Quantitatively, the most important bacterial biotransformation is the 7 alpha-dehydroxylation of CA and CDCA yielding deoxycholic acid and lithocholic acid, respectively. The 7 alpha-dehydroxylation of CA occurs via a novel six-step biochemical pathway. The genes encoding several enzymes that either transport bile acids or catalyze various reactions in the 7 alpha-dehydroxylation pathway of Eubacterium sp. strain VPI 12708 have been cloned, expressed in Escherichia coli, purified, and characterized. PMID- 9990727 TI - A structural comparison of molybdenum cofactor-containing enzymes. AB - This work gives an overview of the recent achievements which have contributed to the understanding of the structure and function of molybdenum and tungsten enzymes. Known structures of molybdo-pterin cofactor-containing enzymes will be described briefly and the structural differences between representatives of the same and different families will be analyzed. This comparison will show that the molybdo-pterin cofactor-containing enzymes represent a very heterogeneous group with differences in overall enzyme structure, cofactor composition and stoichiometry, as well as differences in the immediate molybdenum environment. Two recently discovered molybdo-pterin cofactor-containing enzymes will be described with regard to molecular and EPR spectroscopic properties, pyrogallol phloroglucinol transhydroxylase from Pelobacter acidigallici and acetylene hydratase from Pelobacter acetylenicus. On the basis of its amino acid sequence, transhydroxylase can be classified as a member of the dimethylsulfoxide reductase family, whereas classification of the tungsten/molybdenum-containing acetylene hydratase has to await the determination of its amino acid sequence. PMID- 9990728 TI - Biochemistry of coenzyme B12-dependent glycerol and diol dehydratases and organization of the encoding genes. AB - Glycerol and diol dehydratases exhibit a subunit composition of alpha 2 beta 2 gamma 2 and contain coenzyme B12 in the base-on form. The dehydratase reaction proceeds via a radical mechanism. The dehydratases are subject to reaction inactivation by the substrate glycerol which is caused by a cessation of the catalytic cycle because coenzyme B12 is not regenerated, instead 5' deoxyadenosine and a catalytically inactive cobalamin are formed. The genetic organization of the dehydratase genes is quite similar in all organisms. Downstream of the dehydratase genes an open reading frame encoding a polypeptide of approximately 600 amino acids was identified which is apparently involved in the reactivation of suicide-inactivated enzyme. PMID- 9990729 TI - Comparison of gene structures and enzymatic properties between two endoglucanases from Humicola grisea. AB - We have cloned two endoglucanase genes (egl3 and egl4) from a thermophilic fungus, Humicola grisea. The coding region of the egl3 gene was interrupted by an intron of 56-bp, and the deduced amino acid sequence of the egl3 gene was 305 amino acids in length and showed 98.4% identity with Humicola insolens EGV. The coding region of the egl4 gene was also interrupted by an intron of 173-bp, which contains 34 TTC repeated sequence units, and the deduced amino acid sequence of the egl4 gene was 227 amino acids in length and showed 61.5% identity with H. grisea EGL3. The typical hinge and the cellulose-binding domain were observed in the C-terminal region of EGL3, but they were not observed in EGL4. In the 5' upstream region of both genes, there were a TATA box or its similar sequence, CAAT motifs, and 6-bp sites which are identical or similar to the consensus sequence for binding a catabolite repressor CREA in Aspergillus nidulans. The egl3 and the egl4 genes were expressed in Aspergillus oryzae, and the translation products were purified. The fusion protein, EGL4CBD, which consists of a catalytic domain of EGL4 and the C-terminal region of EGL3, was also constructed and produced by A. oryzae, and purified. These enzymes showed relatively high activity toward carboxymethyl cellulose (CMC) and could not hydrolyze p nitrophenyl-beta-D-glucoside and p-nitrophenyl-beta-D-cellobioside. The positive effect of substituting the C-terminal region of EGL4 with that of EGL3 was observed in the hydrolysis of CMC. PMID- 9990730 TI - Biodegradation of benzene, toluene, ethylbenzene, and o-xylene by a coculture of Pseudomonas putida and Pseudomonas fluorescens immobilized in a fibrous-bed bioreactor. AB - A fibrous-bed bioreactor containing the coculture of Pseudomonas putida and P. fluorescens immobilized in a fibrous matrix was developed to degrade benzene (B), toluene (T), ethylbenzene (E), and o-xylene (X) in synthetic waste streams. The kinetics of BTEX biodegradation by immobilized cells adapted in the fibrous-bed bioreactor and free cells grown in serum bottles were studied. In general, the BTEX biodegradation rate increased with increasing substrate concentration and then decreased after reaching a maximum, showing substrate-inhibition kinetics. However, for immobilized cells, the degradation rate was much higher than that of free cells. Compared to free cells, immobilized cells in the bioreactor tolerated higher concentrations (> 1000 mg l-1) of benzene and toluene, and gave at least 16-fold higher degradation rates for benzene, ethylbenzene, and o-xylene, and a 9 fold higher degradation rate for toluene. Complete and simultaneous degradation of BTEX mixture was achieved in the bioreactor under hypoxic conditions. Cells in the bioreactor were relatively insensitive to benzene toxicity; this insensitivity was attributed to adaptation of the cells in the bioreactor. Compared to the original seeding culture, the adapted cells from the fibrous-bed bioreactor had higher specific growth rate, benzene degradation rate, and cell yield when the benzene concentration was higher than 100 mg l-1. Cells in the fibrous bed had a long, slim morphology, which is different from the normal short rod shape found for suspended cells in solution. PMID- 9990731 TI - Dynamics and modeling on fermentative production of poly (beta-hydroxybutyric acid) from sugars via lactate by a mixed culture of Lactobacillus delbrueckii and Alcaligenes eutrophus. AB - The mixed culture system was considered in the present research where sugars such as glucose were converted to lactate by Lactobacillus delbrueckii and the lactate was converted to poly beta-hydroxybutyrate (PHB) by Alcaligenes eutrophus in one fermentor. For the modeling of the effect of NH3 concentration on the cell growth of A. eutrophus and PHB production rates, metabolic flux distributions were computed at two culture phases of cell growth and PHB production periods. It was found that the NADPH, generated through isocitrate dehydrogenate in TCA cycle, was predominantly utilized for the reaction from alpha-ketoglutalate to glutamate when NH3 was abundant, while it tended to be utilized for the PHB production through acetoacetyl CoA reductase as NH3 concentration decreased. This phenomenon was reflected in the development of mathematical model. In the mixed culture experiments, the two phases were observed, namely the lactate production phase due to L. delbrueckii and the lactate consumption phase due to A. eutrophus. The lactate concentration could be estimated on-line by the amount of NaOH solution and HCl solution supplied to keep the culture pH at constant level. Several mixed culture experiments were conducted to see the dynamics of the system. Finally, a mathematical model which can describe the dynamic behavior of the present mixed culture was developed and the model parameters were tuned for fitting the experimental data. The model may be used for several purposes such as control, optimization, and understanding process dynamics etc. PMID- 9990732 TI - Genetic organization and functional analysis of a novel phage abortive infection system, AbiL, from Lactococcus lactis. AB - A plasmid-encoded phage abortive infection mechanism (AbiL) was identified from Lactococcus lactis biovar. diacetylactis LD10-1. AbiL conferred complete resistance to the small isometric-headed phage phi 712 (936 species) and partial resistance to the prolate-headed phage phi c2 (c2 species) when introduced into L. lactis LM0230. However, AbiL was not effective against the small isometric headed phage ul36 (P335 species). The AbiL determinant was sequenced and it consists of two open reading frames, abiLi and abiLii. Their encoded proteins did not share significant homology with any known proteins in the protein databases. Transcriptional analysis indicated that abiLi and abiLii are organized as a single operon. Deletion within abiLii abolished the phage resistance. The levels of four phi c2-specific transcripts, three within the early transcribed region and one within the late transcribed region, were examined by RT-PCR, no effect of AbiL on synthesis of these transcripts was detected, suggesting that AbiL may act at a point after the transcription of phi c2 in L. lactis. PMID- 9990733 TI - Xylitol production using recombinant Saccharomyces cerevisiae containing multiple xylose reductase genes at chromosomal delta-sequences. AB - Xylitol production from xylose was studied using recombinant Saccharomyces cerevisiae 2805 containing xylose reductase genes (XYL1) of Pichia stipitis at chromosomal delta-sequences. S. cerevisiae 2805-39-40, which contains about 40 copies of the XYL1 gene on the chromosome, was obtained by a sequential transformation using a dominant selection marker neor and an auxotrophic marker URA3. The multiple XYL1 genes were stably maintained on the chromosome even after 21 and 10 days in the non-selective sequential batch and chemostat cultures, respectively, whereas S. cerevisiae 2805:pVTXR, which harbors the episomal plasmid pVTXR having the XYL1 gene, showed mitotic plasmid instability and more than 95% of the cells lost the plasmid under the same culture conditions. In the first batch (3 days) of the sequential batch culture, volumetric xylitol productivity was 0.18 g l-1 h-1 for S. cerevisiae 2805-39-40, as compared to 0.21 g l-1 h-1 for S. cerevisiae 2805:pVTXR. However, the xylitol productivity of the latter started to decrease rapidly in the third batch and dropped to 0.04 g l-1 h 1 in the seventh batch, whereas the former maintained the stable xylitol productivity at 0.18 g l-1 h-1 through the entire sequential batch culture. The xylitol production level in the chemostat culture was about 8 g l-1 for S. cerevisiae 2805-39-40, as compared to 2.0 g l-1 for S. cerevisiae 2805:pVTXR after 10 days of cultures even though the xylitol production level of the latter was higher than that of the former for the first 5 days. The results of this experiment indicate that S. cerevisiae containing the multiple XYL1 genes on the chromosome is much more efficient for the xylitol production in the long-term non selective culture than S. cerevisiae harboring the episomal plasmid containing the XYL1 gene. PMID- 9990734 TI - Feasibility studies of large scale production of human anti-tetanus toxoid monoclonal antibodies. AB - The feasibility of large scale production of human anti-tetanus toxoid monoclonal antibody for therapeutic use was evaluated using a human heterohybridoma. The effects of duration of subculture, transition from static to agitated culture conditions and the level of serum concentration were studied. The level of antibody secreted by the clone decreased with increasing length of subculture and decreasing serum concentration. The clone exhibited heterogeneity in expression of surface IgG after 2 or 7 weeks of subculture in static culture conditions irrespective of the serum concentration. However, a prolonged duration of subculture (9 weeks) in 3% serum medium had an effect on the expression of surface IgG both in static and agitated culture conditions. With respect to total (surface and intracellular) IgG, two distinct cell populations were observed. On long term subculture (9 weeks) in low serum medium (3% FCS), there was a decrease in the population which was the high synthesizer. In addition, when these cells were cultivated in agitated spinner flasks, a defect in secretion of antibodies was observed. Thus a general fall in the amount of antibody in the supernatant of agitated cultures was due to decrease in antibody synthesis as well as the defect in secretion of antibodies. PMID- 9990735 TI - Urea and water permeability in the ureotelic gulf toadfish (Opsanus beta). AB - The permeability of toadfish gills and skin to urea and water has been measured in order to investigate the mechanisms behind the pulsatile excretion of urea previously described in this species. A perfused gill preparation was used in the gill studies and isolated pieces of skin mounted in an Ussing chamber in the skin studies. Simultaneously, urea and water permeability was measured in vivo in free swimming fish. In vivo the nonpulsing urea permeability was exceptionally low compared to other teleosts, while the tritiated water permeability was similar to that of other teleosts. The urea permeability increased 30-fold during a pulse while water permeability stayed unaffected. Compared to in vivo, tritiated water permeability was approximately 50% lower in the gills and the skin when measured directly in the isolated preparations. The urea permeability was almost identical between the three preparations. Four out of 20 perfused gill preparation showed a spontaneous urea pulse during perfusion. Several treatments were tested to elicit the pulse artificially but without success. Hormones and drugs tested were: arginine-vasotocin (AVT), 10(-10) M; adrenaline, 10(-7) M; isoprenaline, 10(-5) M; acetylcholine, 10(-7) and 10(-6) M; serotonin, 10(-7) and 10(-6) M; adenosine, 10(-6) M; cortisol, 10(-7) M; and combinations of AVT, adrenaline, and cortisol. Adrenaline and isoprenaline increased tritiated water permeability without affecting urea permeability. Gradually increasing the ammonia levels in the perfusate from 0.1 mM to 1.6 mM caused a slight increase in water permeability but a marked and progressive increase in urea permeability. No indications of an ammonia trapping mechanism in the gills were found. There was no effect of AVT (10(-10) mol l-1) in the urea permeability of the skin preparation while cortisol (10(-7) M) led to a modest increase in urea permeability. Based on a comparison between the in vivo and in vitro preparations used here, we conclude that the urea pulse in a urea-pulsing toadfish occurs through the gills and not the skin. We still do not know which internal mechanism or signal triggers the urea pulse in the toadfish. PMID- 9990736 TI - Sex reversal by aromatase inhibitor treatment in the newt Pleurodeles waltl. AB - Pleurodeles waltl is a newt with a ZZ male-ZW female sex determination mechanism, and a temperature-sensitive gonadal sex differentiation. Raising larvae at 32 degrees C from stage 42 to stage 54 (thermosensitive period) drives genetic females to differentiate into functional males. Estrogens are intimately linked with temperature action in this species, as well as in other vertebrates with temperature-dependent sex determination. We report here the masculinization of female ZW larvae and one WW larva by aromatase inhibitor treatment. Larvae were treated from stage 52 (before the onset of histological differentiation of the gonads) to stage 56 (metamorphosis), with the non-steroidal inhibitors fadrozole or miconazole. Miconazole proved to be very toxic, but not fadrozole. Fadrozole at a concentration of 300 micrograms/l in the rearing water resulted in complete sex reversal of 9 out of 30 ZW larvae and 1 out 9 WW larvae. Only one individual (ZW) was intersex, all the remainder being typical females. Gonadal aromatase activity was measured in several individuals at different developmental stages during treatment. The activity was low in all individuals at the beginning of the treatment, but varied strongly and was well correlated with gonadal structure at the end of the treatment. Despite these differences in individual responses to treatment inhibiting aromatase, results confirm the important role of estrogens in ovary differentiation in Pleurodeles waltl. PMID- 9990737 TI - Sperm storage in females of the smooth newt (Triturus v. vulgaris L.): I. Ultrastructure of the spermathecae during the breeding season. AB - Sperm storage in cloacal spermathecae was studied in females of Triturus v. vulgaris collected early in the breeding season in southern England. Females collected in terrestrial situations, presumably unmated, were mated in the laboratory, and the ultrastructure of the transferred sperm and the spermathecae was observed at various intervals after mating. Sperm from a spermatophore cap lodged in a female's cloacal orifice can migrate into spermathecae within 1 hr after mating. Spherical structures on the axial fibers of some sperm in the cap could indicate immaturity. Disorderly clusters of sperm from the cap are still present in the cloacal chamber 12 hr after mating but are absent 24 hr after mating. During storage, sperm often are in tangled masses in the spermathecal tubules. The sperm are coated with spermathecal secretions, and some sperm nuclei were observed embedded in the spermathecal epithelium. Little evidence for spermiophagy early in the breeding season was found. During oviposition, mazes of sperm occur external to the spermathecal orifices, and sperm may be released in this condition onto eggs as they pass through the cloaca. The tangled clusters in which sperm are found from pick-up to oviposition are hypothesized as an adaptation to reduce the effectiveness of sperm competition from the ejaculates of rival males. Additional studies, using the same protocol and covering the entire cycle of sperm storage, are necessary to enable interspecific comparisons leading to phylogenetic hypotheses. PMID- 9990738 TI - Deciliation in the ampulla of the rat oviduct and effects of estrogen on the process. AB - The mechanism by which cells in the ampullae of the rat oviducts undergo rapid deciliation during each estrous cycle and the effects of estrogen on the ciliated cells were examined. Untreated rats were killed on each day of the 5-day estrous cycle, and the ampullae of their oviducts were removed. Other rats were injected subcutaneously each day for 5 days with 0.3 microgram or 3.0 micrograms of estradiol benzoate or with 0.3 mg of tamoxifen, an estrogen antagonist, per kilogram of body weight. The ampullae of the oviducts of the treated rats were excised on the day following the last injection. The tissues from all the rats were fixed in glutaraldehyde, stained with uranyl acetate and lead citrate, and examined with a transmission electron microscope. Deciliation of cells was seen to occur by membrane-bound cilia packets (CPs) forming at the apices of cells and pinching off. Although CPs were more numerous at proestrus, they were also observed at estrus, diestrus-1, and diestrus-2, suggesting that the process of deciliation is an ongoing one that merely changes in rate. No evidence of resorption of cilia was seen. Estradiol treatment did not prevent CPs from forming, nor was tamoxifen treatment associated with any apparent enhancement of deciliation. Ciliated cells with CPs stained more darkly than ciliated cells that were without CPs, and the former appeared similar in their staining characteristics to secretory cells, most of which stain darkly. It was concluded that the cells of the ampulla deciliate rapidly by shedding their cilia into the lumen of the oviduct, that estrogen does not halt the process, and that ciliated cells may be transformed to secretory cells following loss of their cilia. PMID- 9990739 TI - Evidence for the presence of a mammalian-like cholinesterase in Paramecium primaurelia (Protista, Ciliophora) developmental cycle. AB - By histochemical and immunohistochemical methods, the presence of cholinergic like molecules has previously been demonstrated in Paramecium primaurelia, and their functional role in mating-cell pairing was suggested. In this work, both true acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) activities were electrophoretically investigated, and the presence of molecules immunologically related to BuChE was checked by immunoblotting. The AChE activity, shown in the membrane protein fraction of mating-competent cells and in the cytoplasmic fraction of immature cells, is due to a 260-kDa molecular form, similar to the membrane-bound tetrameric form present in human erythrocytes. This AChE activity does not appear in either the cytoplasmic fraction of mating competent cells or in the membrane protein fraction of immature cells. No evidence was found for the presence or the activity of BuChE-like molecules. The role of AChE in P. primaurelia developmental cycle is discussed. PMID- 9990740 TI - A quantitative model of the Simpson-Baldwin Effect. AB - G. G. Simpson was the first to explain the Baldwin Effect completely in terms of the theory of natural selection. A genetic version of a seemingly non-hereditary adaptation may arise when natural selection acts on the likelihood of having an adaptive trait not just on the trait itself. We present a quantitative model of the Simpson-Baldwin Effect. Organisms in the model have mutable ranges of phenotypic plasticity. The distribution of phenotypes in a population depends largely on the extent of environmental stochasticity. When the environment undergoes intermediate rates of fluctuation, the Simpson-Baldwin effect arises through the interaction of natural selection and mutation on norms of reaction. In a highly volatile environment, organisms benefit from plasticity, and consequently do not experience a Simpson-Baldwin channeling of phenotypic possibility. PMID- 9990741 TI - Mathematical modelling of tumour acidity: regulation of intracellular pH. AB - Measurements of extracellular pH (pHe) in vivo have shown that the microenvironment in tumours is more acidic than in normal tissue. However, both human and animal tumour cells have been shown to have an intracellular pH (pHi) on the alkaline side of neutrality (pH 7.1-7.2). This gives rise to a reversed pH gradient between tumours and normal tissue which implies that cells within solid tumours are capable of maintaining their level of pHi at physiological levels, despite lower than normal levels of pHe. In this paper the authors describe a mathematical model that provides a possible explanation for the altered pH gradient observed in tumours. The authors examine the influence of changes in the microenvironment on the activity of several membrane based ion transport systems. Using qualitative analysis the authors show that the pHi of tumour cells is less sensitive to external pH than for normal cells, because of their increased reliance on the inefficient glycolytic pathway for energy production. It is shown that under aerobic conditions the lactate-/H+ symporter could be the most active exchanger in the regulation of pHi in tumour cells. However, under more hypoxic conditions lactate extrusion is reduced, and so this exchanger has little effect on resting pHi in these regions. The authors also consider an extended model which incorporates the transfer of acids from the cytosol into acidic organelles. The model demonstrates that one of the major factors involved in the maintenance of cytosolic pH to physiological levels, despite an acidic extracellular pH in hypoxic areas of tumour tissue (median, 6.9-7.0), is enhanced sequestration of cytosolic protons into acidic cellular vesicles such as endoplasmic reticulum, golgi, endosomes, and lysosomes. PMID- 9990742 TI - The effects of suppressing trauma-related thoughts on women with rape-related posttraumatic stress disorder. AB - A hallmark symptom of posttraumatic stress disorder (PTSD) is the presence of intrusive thoughts that come to mind against an individual's will and are frequently accompanied by considerable distress. This investigation examined the effects of deliberate suppression of rape-related thoughts on female sexual assault survivors, in order to explore this facet of PTSD. Seventeen women with chronic PTSD following a sexual assault were contrasted with nineteen survivors without PTSD, using a thought suppression paradigm (e.g. [Wegner, Schneider, Carter, & White (1987) Paradoxical effects of thought suppression. Journal of Personality and Social Psychology, 53 5-13]). Results indicated that PTSD participants experienced a rebound in the frequency of rape-related thoughts following deliberate suppression, whereas non-PTSD participants did not experience a rebound. Reported level of perceived controllability over rape related thoughts for the PTSD participants was significantly lower during the suppression phase (as compared with the expression phase) relative to the non PTSD participants. PTSD participants were significantly more anxious, depressed and distressed throughout the procedure relative to non-PTSD participants, although mood changes did not parallel the rebound effect found with rape-related thoughts in the PTSD group. Results are discussed in light of the role that intrusive thoughts may play in the maintenance of PTSD. PMID- 9990743 TI - Obsessive-compulsive disorder subgroups: a symptom-based clustering approach. AB - Although obsessive-compulsive disorder (OCD) is often considered a heterogeneous condition, there is no generally accepted subtype typology. Cluster analysis was used to identify definitive symptom-based groupings of 106 OCD patients. A stable cluster solution was achieved and five patient subgroups were identified based on their pattern of symptoms on the Yale-Brown (Y-BOCS) symptom checklist: harming, hoarding, contamination, certainty and obsessionals. The five subgroups were characterized by dominant symptom patterns and significant secondary concerns reflecting the symptom heterorgenaity often seen in the clinical presentation of obsessional patents. Between cluster differences on multiple symptom measures were evaluated and several meaningful differences were identified. Cluster analytic procedures may prove to be a useful tool for identifying a functional taxonomy of OCD subtypes. PMID- 9990744 TI - The value of the Parenting Scale for measuring the discipline practices of parents of middle school children. AB - The psychometric properties of the Parenting Scale (Arnold, O'Leary, Wolff, and Acker, 1993), a 30-item instrument originally developed to assess the discipline practices of parents of preschool children, were examined for parents of middle school students. Subjects were 298 parents of middle school student identified as at-risk for problem behavior. An exploratory factor analysis identified two factors labeled 'Overreactivity' and 'Laxness', closely resembling two of the factors found by Arnold et al., but each of these factors contained only six items. Confirmatory factor analyses, using data from the first two assessments, replicated this factor structure. The factors were significantly correlated with measures of parents' behavior, with scales from the child Behavior Checklist and Parent Daily Reports, and with the Beck Depression Inventory. The Laxness factor was less robust than the Overreactivity factor. PMID- 9990745 TI - The absence of relation between anxiety sensitivity and fear conditioning using 20% versus 13% CO2-enriched air as unconditioned stimuli. AB - Anxiety sensitivity has been implicated as a risk factor in the development and maintenance of anxiety and fear-related disorders. Indeed, persons who score high on the anxiety sensitivity index (ASI) are generally more responsive to biological challenge procedures such as CO2-inhalation that directly evoke the feared bodily events. One would expect, therefore, that persons high on anxiety sensitivity should be more conditionable and hence more likely to acquire fears, than persons low on anxiety sensitivity when CO2-enriched air is used as an unconditioned stimulus (UCS). Undergraduates (N = 96), scoring high, medium and low on the ASI received 8 repeated 20-s inhalations of either 20 or 13% CO2 enriched air (UCSs) paired with one of three CSs differing in fear-relevance (snake, heart and flowers). Several autonomic and self-report measures were assessed. Contrary to expectation, electrodermal and cardiac conditioned responses failed to discriminate between ASI groups. Yet, SUDS and severity and frequency of DSM-IV panic symptoms varied reliably as a function of anxiety sensitivity. Overall, the findings suggest that anxiety sensitivity is related to subjective fear-related complaints, but not autonomic responding and conditionability. We discuss clinical and theoretical implications for understanding the place fo anxiety sensitivity in fear onset. PMID- 9990746 TI - Evidence for fear of restriction and fear of suffocation as components of claustrophobia. AB - Recent investigations of the aetiology and treatment of specific phobias have focused on clarifying the concerns underlying phobic anxiety. It has been proposed that claustrophobic fear is comprised of separable confinement and suffocation components. This paper presents data from 78 general medical outpatients undergoing magnetic resonance imaging (MRI) scans in two major teaching hospitals. The findings support the two factor structure of claustrophobia, in that exposure to confinement reduced confinement subscale scores, but did not influence suffocation scores. PMID- 9990747 TI - Obsessive compulsive disorder, checking, and non-verbal memory: a neuropsychological investigation. AB - There is considerable evidence in the literature for the presence of non-verbal and praxic memory deficits in OCD. Such deficits may represent the cognitive substrate of doubt-related phenomenon such as checking. Neuropsychological tests of non-verbal memory functioning and memory for actions were administered to patients with OCD (whose predominant symptom was checking) and a group of matched healthy controls. Significant differences were found between the experimental and control groups, suggesting some memory impairment in the OCD group; however, no significant relationship was found linking neuropsychological test indices with checking. Significant relationships were found linking recognition memory problems and immediate memory for actions with general symptom severity. PMID- 9990748 TI - Psychometric properties of the Multidimensional Pain Inventory, Dutch language version (MPI-DLV). AB - The purpose of this study was to investigate the psychometric properties of a Dutch translation of the Multidimensional Pain Inventory, MPI-DLV. Data was available on 733 chronic pain patients. There were three issues of special interest. The first one related to the comparability between the MPI-DLV and the American and German MPI versions with regard to the psychometric aspects. The second dealt with the construct validity of the MPI-DLV scale 'general activity'. It was predicted that patients with high scores on this scale would be in better physical condition, as measured on a working-to-tolerance bicycle ergometer test. In relation to the third issue, attention was given to the factor-invariance between fibromyalgia patients and back pain patients. From the results obtained it was concluded that (1) the factorial structure of the three MPI parts is replicated and the reliability estimates and validity indicators are similar to those from the American and German versions; (2) patients with high scores on the 'general activity' scale are in better physical condition and (3) MPI-DLVs of fibromyalgia and back pain patients do have similar factorial structures. Evidence was also obtained that the MPI-DLV is sensitive to treatment changes. Applications of the MPI-DLV are discussed. PMID- 9990749 TI - Common and specific dimensions of self-reported anxiety and depression: the BDI II versus the BDI-IA. AB - The Beck Depression Inventory-II (BDI-II) [Beck, A. T., Steer, R. A. & Brown, G. K. (1996). Manual for Beck Depression Inventory-II. San Antonio, TX: Psychological Corporation.] and Anxiety Inventory (BAI) [Beck, A. T. & Steer, R. A. (1993a). Manual for the Beck Anxiety Inventory. San Antonio, TX: Psychological Corporation.] were administered to 840 outpatients who were diagnosed with various types of psychiatric disorders to determine whether the general symptom compositions and relative amounts of variance of the common and specific dimensions of self-reported anxiety and depression for these instruments would be comparable to those that had been found by Steer et al. [Steer, R. A., Clark, D. A., Beck, A. T. & Ranieri, W. F. (1995). Common and specific dimensions of self reported anxiety and depression: A replication. Journal of Abnormal Psychology, 104, 542-545.] with the BAI and amended Beck Depression Inventory (BDI-IA) [Beck, A. T. & Steer, R. A. (1993b). Manual for the Beck Depression Inventory. San Antonio, TX: Psychological Corporation.]. A Schmid-Leiman transformation was used with the iterated-principal-factor pattern matrix of the BAI and the BDI-II loadings and indicated that the overall symptom compositions and relative amounts of variance that were explained by the one common and two specific anxiety and depression dimensions were comparable to those previously found with the BDI-IA. PMID- 9990750 TI - Visions: our hopes for the future. PMID- 9990751 TI - The Robert Tiffany Lectureship. Vital signs at the millennium: becoming more than we are. AB - Presenting this lecture named for my colleague, the late Robert Tiffany, is an honor. He was part of the first International Conference on Cancer Nursing 20 years ago, which was my first international meeting. It was part of what expanded our Texas--only cancer prevention and detection program for nurses into an international effort. Lessons acquired through this work in the past include learning to respect and honor cultural differences, adapting control programs to the resources at hand, accepting a role as a leader and being an agent for change, and passing on what has been learned to others. The challenges of today include the worldwide death and disability toll of lung cancer, the threat of breast cancer and the promise of regular screening to lower its morbidity and mortality, and the hope that a willingness to adapt screening for cervical cancer in developing countries will lower its mortality rate. Twenty years in the future we can expect nurses to remain educators, exemplars, and agents of change; cancer prevention and early detection to rise in the hierarchy of care; continued collaborative care between physicians and nurses; enhanced patient care through information access; and a larger role for cancer genetics in nursing practice. PMID- 9990752 TI - Schering Plough clinical lecture communication: it makes a difference. AB - Communication is a vital component of nursing care that can improve outcomes for patients with cancer and their families in terms of psychological distress. Research indicates that nurses' communication skills have shown little improvement over the last 20 years. Communication is a practical skill that can be learned in theory from the literature or educational programs, but putting theory to practice in the clinical setting is far more problematic. Nurses need to be aware of their own communication skills by listening to themselves and learning from their mistakes. Only with this practice will skills improve. Communication can make or mar a person's illness experience. It is time for nurses to take effective communication seriously and actively accept personal responsibility for their actions because there is clear evidence showing that good communication makes a difference for patients and their families. PMID- 9990753 TI - Prevention: tobacco control and cancer nursing. AB - In the next century, tobacco will become the number-one cause of preventable death throughout the world, resulting in half a billion deaths. As global patterns of tobacco use change, tobacco-related morbidity and mortality will shift from developed countries to developing countries. Internationally, lung cancer will become the fifth leading cause of preventable death, affecting an increasing number of women. Tobacco cessation after a diagnosis of cancer may decrease treatment-related morbidity and increase survival. With the increasing number of cancer survivors, tobacco cessation becomes an important part of rehabilitation. This article aims to provide a foundation for developing strategies to involve cancer nurses throughout the world in an international campaign to prevent tobacco-related morbidity and mortality. The devastating health impacts of tobacco are reviewed, and highlights of new scientific findings about nicotine addiction are presented. New approaches to tobacco prevention, legislation, and regulatory policies are discussed. Tobacco assessment strategies and treatment interventions for use in cancer nursing clinical practice are reviewed, and global strategies for nursing action in tobacco control are offered. PMID- 9990754 TI - New strategies in the management of cancer. AB - The developing knowledge of cancer is paving the way for a new era of management of this disease. New scientific knowledge has enabled different and exciting modes of cancer therapy to be tested in the clinical setting. These innovations will lead to the availability of novel cytotoxic agents in the near future. In addition to such agents, the last few years has seen the emergence of new radiotherapy and surgical techniques that have the potential to radically change nursing practice. Such developments require a knowledgeable nursing workforce who can provide anticipatory care in tandem with supportive care strategies to facilitate optimal patient outcomes. This article considers potential future developments in cancer management and raises the issue of nursing being integral to the treatment process. PMID- 9990755 TI - Global perspectives on palliative care. AB - The modern hospice movement had its formal beginnings in the United Kingdom with the 1967 opening of the St. Christopher's Hospice in London by Dame Cicely Saunders. Global uptake of the hospice principles and, more recently, palliative care, is widespread. However, the movement has shifted from charismatic, charity based, and independent hospices to routinized and increasingly bureaucratized palliative care. Global differences exist around the degree to which hospice and palliative care are established components of the health care system. Access appears to increase with the integration of services into mainstream health funding. The downside of this is increased regulation, competition, and a potential loss of specificity for those who are dying. This article explores the changing face of palliative care, with particular emphasis on palliative care delivery in the developing world. These issues for developing countries include access to services, access to morphine, and professional access to information and education. PMID- 9990756 TI - Cultural views of cancer around the world. AB - Social attitudes toward cancer, participation in early detection and screening services, and compliance with treatment are all known to be profoundly affected by cultural beliefs and norms. It is thus imperative that oncology nurses develop cultural competence and deliver culturally sensitive care. Cross-cultural nursing studies also require cultural sensitivity because they rely on the accurate choice of culturally relevant research methods. However, the specific steps that should be taken to enhance the cultural relevance of both nursing health care delivery and nursing research have yet to be elaborated. This article aims to clarify these issues on the basis of a critical survey of the literature on cultural views of cancer in multiethnic societies and in various countries around the world. The analysis of studies focusing on this subject illuminates misconceptions that may interfere with the application of cancer nursing to other cultures, and possible misinterpretations of cultural and cross-cultural research findings. The conclusions drawn from this analysis concern practical means for facilitating nurses' ability to properly address cultural diversity through the incorporation of culture-related variables into nursing interventions. They also relate to the education of nurses about cross-cultural aspects of cancer, culturally sensitive assessment tools, comparative studies, and theories in the field of international cancer nursing, all of which await further development. PMID- 9990757 TI - From the desert: transcultural aspects of cancer nursing care in Israel. AB - Quality of life perceptions, the meaning of cancer perception, and the meaning of illness are culture bound. Culture includes learned and shared ways of interpreting the world and interacting in society, and thereby provides all individuals with ideas about what is good or bad, desirable or undesirable, valued or devalued in life. Israel is an immigration country, and its citizens came from all over the world. It is also a meeting zone between Middle Eastern traditional culture and Western modern medicine. Cancer patients and a substantial proportion of doctors, nurses, and other health care professionals are from different ethnic backgrounds. In hospitals, clinics, and other places where health professionals live, work, or relax, there is a network of cultural factors that plays an important role in the well-being of patients. Cultural effects can considerably complicate the assessment of how an individual is likely to react to various aspects of the hospital environment, medical condition, treatment, staff, fellow patients, and so on. Ideal management includes the foresight to forestall problems that may arise and to create favorable psychosomatic effects that help patients to respond positively to treatment. To illustrate the cultural component in nursing care, four cancer patients from totally different cultural backgrounds are described: a bedouin, an Israeli-born Jew whose parents immigrated from Tunisia, and two immigrant patients, one from the United States and the other from Ethiopia. All four patients were treated by chemotherapy, radiation, or both in an oncology day-care unit at the Soroka Medical Center in Beer-Sheva. Also, a special education program for immigrant nurses is presented, as well as a new immigrant nurse from the former Soviet Union. PMID- 9990758 TI - The experience of having cancer in Latin America. AB - When the human experience is reduced to basic feelings, it becomes evident that the impact of cancer produces similar responses in people around the world. These responses are affected by the individual's culture, myths, and beliefs. Latin America includes several countries, each with different traditions and backgrounds. This article illuminates common cultural health beliefs in Latin America that play a significant role in the way Latin Americans perceive the experience of cancer. Nurses providing care to cancer patients should be aware of cultural differences and familiar with the lifeways of the major cultural groups in order to meet the needs of the patients under their care. PMID- 9990759 TI - When mom's sick: changes in a mother's role and in the family after her diagnosis of cancer. AB - As social entities, individuals enact roles and carry out responsibilities. Roles are learned and influenced by many social forces. They give meaning and value to life and foster a sense of belonging and contribution. Roles can undergo profound transformation during and after a diagnosis of cancer. In most family situations, the role of mother is a significant caretaking role. However, little research has focused on understanding the alterations that can occur in the mother's role when a woman faces cancer. The purpose of this study was to explore, from a woman's perspective, the experience of being a mother living with life-threatening illness. In-depth interviews were held with 47 mothers diagnosed as having cancer. Their children ranged in age from 1 to 18 years. Content and theme analyses were performed on the transcribed texts. The findings describe the impact of the cancer on the women and their families and how they felt about any changes in their roles as mothers. PMID- 9990760 TI - Family coping: issues and challenges for cancer nursing. AB - A large body of research now exists suggesting that families are dramatically affected by a diagnosis of cancer, and that they have a wide range of support needs. In particular, evidence suggests that the emotional strains of living with a family member who has cancer are an especially difficult coping challenge, and that such strains have a significant impact on the day-to-day lives of family members. Despite this evidence, there has been little analysis to date on the nature of the families' experience with cancer and what implications the unique features of family relationships and interactions in the context of cancer have for nursing practice. Some of these specific features of the families' experience with cancer are examined in this article. It is suggested that enormous scope exists for improving nurses' contribution to care for families of people with cancer. Specific recommendations for achieving such improvements include a critical review of the constraints that exist on efforts to care for families, and the development of approaches to care that appreciate the interconnectedness of family responses and the considerable needs of family members for emotional and practical support. PMID- 9990761 TI - A test of parenthood: dilemmas of parents of terminally ill adolescents. AB - This article presents partial findings from a study that examined the process experienced by parents (mainly mothers) of an adolescent child with terminal cancer. It focuses on two processes that characterize the parents' social world: a crisis in the parental role and a departure from the normative life cycle. These processes, and the parents' coping with them, were studied from the perspective of time and time management. One of the study's claims was that the terminal disease alters the definition of parenthood and causes the parents to depart from the normative life cycle. The study's purpose was to find and explain the coping patterns used by the parents of terminally ill adolescents. This article focuses on two of the various side effects discovered: the distortion of the subjects' time world and the test of parenthood. PMID- 9990762 TI - Learning to live with cancer in European countries. AB - Patient group education is an evidence-based and powerful intervention for supporting and guiding patients toward an understanding of the cancer experience. An education program for patients and families, entitled Learning to Live With Cancer, has been developed and evaluated in a Swedish research project, and implemented clinically. The program is a core model with a structure that allows flexibility in addressing learning needs. It has grown into a pan-European program through "training the trainers" courses, and is now available in many countries. This has taken the project into a new phase, since Europe is characterized not only by showing many different countries, but also by showing cultural diversity and variety in ethical norms. The aim of this phase thus was to assess the presence of core-model divergences conditioned by cultural values and norms, and if present, to investigate adjustments proposed to increase the relevance of the program to best suit patients' learning needs in different cultures. A questionnaire was distributed to former participants in "training the trainers" courses. The findings indicate that only minor divergences are present, and that the core model thus has the potential to meet the learning needs of cancer patients in many cultures. PMID- 9990763 TI - Complementary therapies: overview and state of the art. AB - Studies to determine the prevalence of complementary and alternative medicine (CAM) use among cancer patients show international interest in a wide collection of therapies and a broad span of use, ranging from 7% to 64% of patients sampled. The absence of consistent results across studies is due primarily to differing definitions of unconventional cancer therapies from study to study. Treatments promoted as alternatives to mainstream cancer cures (e.g., the recently disproved "cancer cure" of Italy's Dr. Di Bella) should be distinguished from complementary therapies, which are applied as adjuncts to mainstream care in an integrated fashion. The latter include mind-body techniques and herbal remedies, among many other remedies, all aimed at symptom control and enhanced quality of life. This differentiation provides a clearer understanding of CAM activity and enables selective evaluation of CAM's clinical effects. It permits us to avoid accepting or rejecting all of CAM out of hand. Health care professionals as well as patients and their families have become increasingly knowledgeable about complementary therapies that can be helpful to patients with cancer. Many such therapies have been well studied (meditation, tai chi), and others remain highly questionable (homeopathy, electromagnetics). Their benefits and potential problems are reviewed. PMID- 9990764 TI - Oncology nurses' perspectives on unconventional therapies. AB - Unconventional therapies have become increasingly popular with health care consumers in recent years. As patients seek information and attempt to make decisions about unconventional therapies, they often turn to nurses, asking their opinion about certain therapies. The nurse's attitudes and beliefs about unconventional therapies very likely will influence the response to the patient's inquiries. This work represents the findings of interviews with 48 nurses regarding their perspectives on unconventional therapies. Without exception, all nurses interviewed emphasized the need for information regarding unconventional therapies to be readily available for patients and health care professionals. The other themes identified in the interviews included the following: various people use unconventional therapies; people seek unconventional therapies for a variety of reasons; communication about unconventional therapies needs to be open; and conventional and unconventional practitioners ought to work collaboratively. The participants interviewed saw a clearly defined role for nurses regarding unconventional therapies. PMID- 9990765 TI - The family history component of cancer genetic risk counseling. AB - Family history is an important risk factor for inherited cancers. Obtaining a family history is therefore a key component of cancer genetic risk counseling (CGRC). Many oncology nurses do not have training in cancer genetic risk counseling. However, every nurse is capable of obtaining a basic family history. The family history can help in identifying patterns of cancer transmission in families. Nurses can then refer families with a strong history of cancer to nurse geneticists, genetic counselors, or others qualified to make a further assessment of risk. If those resources are unavailable locally, the Internet can be of assistance. This article summarizes genetic and clinical characteristics of inherited cancers, the significance of family history, interview approaches, questions to ask about personal and family history of cancer, what a pedigree is and how to draw one, what to do with family information including risk analysis and documentation, and available resources on the Internet. PMID- 9990766 TI - Dohi Memorial Lecture. From occlusive to living membranes. PMID- 9990767 TI - The UV-induced SOS response: importance to aging skin. PMID- 9990768 TI - Pathogenesis of psoriasis. PMID- 9990769 TI - Digital images in dermatology and the Dermatology Online Atlas on the World Wide Web. AB - The digital revolution opens new ways of storing, retrieving and distributing images. The informativeness of digital images of dermatological conditions as compared to conventional photographs and slides has proven to be statistically similar; in many cases, digital images may even substitute for dermatologic physical examination. Current developments in high-speed, high-capacity international networks and the growing popularity of the World Wide Web are converging in ways that have great potential for enhancing access to biomedical information, including medical images. However, lack of metainformation and indexing services specialised in retrieving images makes finding images--as opposed to textual information--on the Web difficult. To provide an image collection and entry point into dermatological resources on the World Wide Web, we have developed an image database (Dermatological OnlIne Atlas--DOIA). The database, which is freely available on the Internet at http://dermis.net, contains about 3,000 clinical images covering more than 600 dermatological diagnoses. It is designed for worldwide use; international submissions are encouraged. It serves as a teaching tool for medical students, doctors and patients, assists professional users by being an easy gateway to other databases such as MEDLINE, PDQ, and OMIM and serves as a platform for conducting research by means of administering Internet surveys to users. We conclude that an online image atlas has multiple educational, clinical, and research applications. PMID- 9990770 TI - Strategy for treatment of psoriasis: systemic treatments. PMID- 9990771 TI - Principles of hair cycle control. AB - The hair follicle (HF) undergoes life-long cyclic transformations between "resting" (telogen), growth (anagen), and apoptosis-driven regression (catagen). Contrary to conventional wisdom, cyclic remodelling affects even the distal HF epithelium; telogen is not a mere resting period, since it shows substantial metabolic and proliferative activity and may encompass a phase of controlled hair shaft-extrusion ("exogen"). Even under physiological circumstances, very few (malfunctioning?) HF may leave this cycle over time to be removed by inflammatory cells ("programmed organ deletion"). Although numerous systemic, metabolic, immunological, and nerve-derived factors (e.g. hormones, cytokines, neuropeptides, neurotransmitters, mast cells) can profoundly alter hair growth in vivo, neither vascular nor neural stimuli nor extrafollicular cells are essential for HF development or cycling. Rather, an intrafollicular "hair cycle clock" of as yet unknown nature drives the HF cycle. This elusive chronobiological timing device likely exploits secondary changes in the intra- and perifollicular signalling milieu for guiding the HF through its transformations. However, the supreme generator of cycling activity ("oscillator") that dictates any of these signalling switches is still as unknown as is its exact location. Since, clinically, the control of catagen is of paramount importance (too early anagen termination: alopecia, effluvium; catagen too late: hirsutism, hypertrichosis), the controls of catagen-associated keratinocyte apoptosis and of dermal papilla secretory activities are discussed as crucial targets for future therapeutic manipulations. PMID- 9990772 TI - Dermagraft treatment of diabetic ulcers. PMID- 9990774 TI - Apligraf treatment of venous ulcers and other chronic wounds. PMID- 9990773 TI - The use of Apligraf in acute wounds. AB - Advances in the development of tissue engineered skin have led to several new products aimed at improving wound healing. Designed as a skin substitute, both epidermal and dermal equivalents have been under investigation and used clinically for over a decade. A novel bi-layered living skin equivalent, Apligraf, has been approved in several countries and is approval in the US FDA for the treatment of venous ulcers. Derived from foreskin, cultured neonatal fibroblasts are combined with bovine type I collagen to form a neodermis over which cultured neonatal keratinocytes are placed, proliferate and differentiate. In addition to use in venous ulcers, Apligraf use has also been reported in acute wounds such as surgical excision sites and partial thickness donor sites. Apligraf's use in acute wounds has lent insight into its biologic behavior, safety and efficacy. Through these experiences, it has been learned that Apligraf behaves similar to a partial thickness autograft, and is safe and effective. In addition, Apligraf appears to 'take', in many cases persists, is not clinically rejected but its ultimate fate is not known. PMID- 9990775 TI - Dermatology in the U.K. PMID- 9990776 TI - Dermatology in Germany. AB - In Germany, dermatology has a long tradition as a medical specialization. The first dermatological university departments were established about 120 years ago. From the beginning, venerology was integrated in this field. Today it also covers andrology, allergy, medical cosmetology, mycology, dermatosurgery, phlebology and photodermatology. This broad spectrum more and more gives rise to competition with other medical fields. About 77% (n = 3281) of all German dermatologists (n = 4240 in 1997) work in private practices. The others are employed in clinical departments. The official number of working physicians in Germany in 1997 was 343,556; about 1.5% of them were dermatologists. This means that one dermatologist takes care of 20,000 people. The overwhelming majority of dermatological patients directly contacts the specialist and are not referred by general practitioners (GPs) who comprise about 40% of all German physicians. This is a great advantage over those countries in which patients primarily have to consult the GP. At present, there is a discussion initiated by GPs to change this system in Germany and to reestablish the GP's role as "gatekeeper". Dermatologists together with other specialists are trying to prevent this an to maintain the traditional broad spectrum of German dermatology. PMID- 9990777 TI - Dermatology in France. PMID- 9990778 TI - Dermatology in the U.S.A. PMID- 9990779 TI - Korean Dermatological Association. AB - The Korean Dermatological Association (KDA) was founded on October 27, 1945. The first annual meeting was held on November 15, 1947, and meetings have been held twice a year since 1975. The KDA 50th Annual Spring Meeting was on April 15-16, 1998. Korean Journal of Dermatology, the official journal of the KDA, was first published in 1960 and has been published bimonthly since 1978. Annals of Dermatology (Seoul), the English journal, was first published in 1989 and has been published quarterly since 1995. The American residency and specialty board system was introduced in 1954. Board specialty examination of dermatology candidates by the KDA requires four years of residency. Three hundred and twenty residents are now in the training course in the fifty-nine resident training approved hospitals this year. KDA has seven regional dermatological societies; Seoul, Pusan, Taegu, Honam, Chungchong, Jeonbuk, and Kangwon. KDA has had eleven research subcommittees since 1981. There are two associated societies of the KDA; the Korean Society for Investigative Dermatology was founded in 1991, and the Korean Society for Medical Mycology was founded in 1994. The Korea-Japan Joint Meeting of Dermatology has been held every two years since 1979 and the Korea China Joint Meeting of Dermatology and Mycology has been held since 1996. About three hundred papers were presented at the 49th Annual Autumn Meeting on October 21-23, 1997. These included special lectures, invited lectures, educational lectures, oral presentations, and posters. About five hundred dermatologists participated in that meeting. KDA joined the International League of Dermatological Societies in 1973 with forty-seven members. There are around 1200 members of the KDA including 320 residents in 1998. PMID- 9990781 TI - Nurses in surgery--opportunity or threat? A personal view. PMID- 9990780 TI - Academic teaching and research: dermatology in Germany. PMID- 9990782 TI - The management of femoral and tibial diaphyseal fractures. PMID- 9990783 TI - Use of a general surgical high dependency unit in a district general hospital: the first 10 years. AB - The high dependency unit (HDU) is a facility that is an essential component of any surgical unit. This paper reviews the development of a general surgical HDU managed by surgeons over a decade, with analysis of activity from 1991 to 1996. The general surgical workload has increased during the 10-year period, and the case-mix has become richer by an increase in vascular surgery. The HDU provides essential post-operative care to major surgical patients and minimizes the cancellation of aortic operations without placing an extra burden on the intensive care services. The HDU centralises sick patients, facilitating their care, and provides a learning environment for trainee surgeons. PMID- 9990784 TI - Can we improve the uptake of gastroscopy in the population at risk for gastric cancer? The effect of home letter information. AB - The poor outlook for gastric cancer in Britain is largely due to late diagnosis. Earlier diagnosis will require both easy access to endoscopy and increased public awareness of dyspeptic symptoms. We used information by personal letter to encourage reporting of potentially significant symptoms in patients over 40 years of age. The aim of this study was to measure the acceptability and effect on gastroscopy rates of home letter information. Patients over 40 registered with 12 general practices were used in the study (practice population 80,000). Patients over 40 from another nine practices (practice population 46,500) acted as controls. A letter encouraging consultation for new dyspeptic symptoms was sent to all study subjects. Gastroscopy rates were compared in both study and control populations. Questionnaires on symptoms were sent to 500 study subjects. The principal outcome measure was the gastroscopy rate in people over 40 in both populations, before and during the intervention. The gastroscopy rate was 23% higher in the study than in the control population during the study (3.32 vs. 2.7%, P = 0.00016, chi 2 = 14.25). Gastroscopy uptake increased by 85% from 1991/2 to 1993/4 in the study group and by 34% in the control group (chi 2 = 14.02, P = 0.00018). Thirty-one per cent of questionnaire respondents had dyspeptic symptoms; only 3% had 'significant' symptoms of between 2 and 52 weeks duration. Home letters are an acceptable and efficient method of increasing gastroscopy uptake in dyspeptic patients over 40. PMID- 9990785 TI - The diagnostic value of symptoms and signs in childhood abdominal pain. AB - The assessment and diagnosis of abdominal pain in childhood continues to be a clinical challenge. We audited the presenting symptoms and signs in a consecutive series of 447 children presenting to a paediatric surgical unit in an attempt to quantify the value of particular symptoms and signs in differentiating acute appendicitis (AA) from non-specific abdominal pain (NSAP). The onset of pain in the centre of the abdomen and radiation of pain was not sufficient to differentiate between NSAP and AA. Progression of pain, nausea, vomiting, anorexia and diarrhoea were significantly more common in children with AA (P < 0.01). Similarly, facial flushing, tachycardia (pulse > 100 beats/min), guarding and rebound tenderness were significantly more common in children with AA (P < 0.001). Knowledge of this quantitative data could help clinicians adjust the weighting given to the presence of a particular symptom or sign in children with acute abdominal pain. PMID- 9990787 TI - Blood utilization in hip and knee arthroplasty: a cost-minimization study. AB - The non-utilization of crossmatched blood is an expensive waste of resources. We have audited blood utilization for all primary total hip and knee arthroplasty patients. We compared routine pre-operative crossmatching (Phase 1) with a policy of group, screen and save (G & S) only (Phase 2). The patient groups were similar in both phases. Pre- and post-operative haemoglobin results were not significantly different between Phase 1 and 2. No adverse transfusion reactions occurred. In Phase 1, 213 units were crossmatched pre-operatively, but only 127 (60%) were transfused. In Phase 2, 117 units were requested and all transfused. The G & S only policy proved to be a safe and practical option which improved the efficiency and cost-effectiveness of blood ordering. Based on a handling charge of 37.50 Pounds per unit of blood by the Regional Transfusion Centre, an estimated annual saving of over 8000 Pounds can be made in our directorate. PMID- 9990786 TI - Local recurrence following rectal resection for cancer. AB - Recurrent rectal carcinoma following surgery carries an extremely poor prognosis and subsequent intervention is usually palliative. The incidence of local recurrence (LR) following curative surgery for rectal cancer has been reported to range from 3.7 to 50%. Current treatment strategy for rectal cancer aims at minimizing LR by either pre-operative radiotherapy or adjuvant chemoradiotherapy. Three hundred and fifty-four patients underwent surgical resection for rectal cancer in our department between April 1989 and March 1994, of which 47 (13%) were Dukes A, 88 (25%) Dukes B, 143 (40%) Dukes C and 76 (22%) Dukes D. Two hundred and seventy-eight (79%) patients were defined as having had curative resection (Dukes A, B and C). Overall, total LR occurred in 43 (12.2%) of 354 patients, while LR following curative resection occurred in 16 (9.4%) of the 278 patients. The incidence of LR became higher with increasing depth of invasion and lymph nodal involvement as shown by its direct relationship to stage of disease: Dukes A (0%), B (5.7%), C (14.6%) and D (22.3%). Local recurrence following resection for rectal cancer in our series is low. Pre-operative radiotherapy or adjuvant chemoradiotherapy may not further reduce this low incidence of LR significantly and its role needs to be re-evaluated for institutions with low local recurrence rates. PMID- 9990788 TI - Meniscal regeneration in the long-term after total meniscectomy? AB - A cohort of 39 patients (28 male, 11 female) that had undergone total meniscectomy as adolescents (mean age 16 years) underwent FISP 3D Magnetic Resonance Imaging at a mean follow up of 30 years. The presence of meniscal tissue was assessed by two independent observers blinded to the operation details. The volume of any meniscal tissue present was calculated. A posterior horn remnant was seen in 57% of medial and 45% of lateral meniscectomy cases. The mean volume of an operated medial meniscal remnant was 0.29 mL compared with a mean volume of 1.15 mL for an intact medial meniscus. The mean volume of an operated lateral meniscal remnant was 0.30 mL compared with 1.07 mL for an intact lateral meniscus. We have shown that the incidence of incomplete excision of the posterior horn is more common after total medial meniscectomy, and that at a mean follow up of 30 years there is no convincing in vivo MRI evidence of long-term meniscal regeneration. PMID- 9990789 TI - To drain or not drain: literature versus practice. AB - To evaluate the current use, of and opinion regarding the use of closed suction drains in orthopaedic practice, a literature review and two surveys have been conducted. Recent literature suggests that there is no difference in terms of wound healing, post-operative pyrexia, range of motion, seroma collection, days of hospitalization and infection rate in drained and undrained groups in routine orthopaedic procedures. In the first survey, a questionnaire was sent to all members of the British Orthopaedic Association, to establish the incidence of the use of drains, their placement and the usual duration of drainage. In the second survey, all the orthopaedic consultants of the Mid-Trent Region were interviewed to establish their reasons for using drains. Both surveys indicate that drains are used routinely by the majority of orthopaedic surgeons regardless of the published literature. We conclude that most orthopaedic surgeons in the United Kingdom do not practice 'evidence-based medicine' with regards to wound drainage. PMID- 9990790 TI - Chymopapain chemonucleolysis: a review of 105 cases. AB - A review of 105 consecutive cases of chymopapain chemonucleolysis for single level lumbar disc herniation was undertaken. Mean follow-up was 12.2 years (range 10-15.3). Patients were assessed using the Oswestry Disability Questionnaire. Eighty-seven patients were available for follow-up. An excellent or good response occurred in 58 patients (67%); four patients (4.5%) had a moderate response but were only minimally disabled. The treatment failed in 25 patients (28.5%) and 21 of these went on to surgery within a mean of 5.2 months (range 3 weeks-12 months). In 15 patients (71%) disc sequestration or lateral recess stenosis was found. Five of the remaining six cases had a large disc herniation at surgery. Surgery resulted in a significant improvement in nine cases. Discitis following chemonucleolysis occurred in six patients (5.7%). Chymopapain chemonucleolysis has a useful role in the management of lumbar intervertebral disc prolapse. However, its efficacy is dependent on careful clinical and radiological patient selection. PMID- 9990791 TI - The painless fracture: could it be TB? AB - Tuberculosis is one of the commonest infections world-wide, with one third of the world's population carrying the bacillus. Since the 1980s the decline in notification rates in the UK has stopped and recently reversed. The reasons for this are multifactorial and are discussed briefly here. We present the case of an unusual presentation of tuberculosis in the metatarsal of an elderly Caucasian gentleman. This serves as a reminder to include tuberculosis in the differential diagnoses of unusual musculoskeletal presentations. PMID- 9990792 TI - Microcystic adnexal carcinoma: a report of three cases. AB - Microcystic adnexal carcinoma is an uncommon adnexal neoplasm. It is highly aggressive locally and its importance lies in the fact that it can be easily confused with benign adnexal tumours, particularly desmoplastic trichoepithelioma, trichoadenoma and syringoma. We report three cases of microcystic adnexal carcinoma of the skin, all three being on the face: two on the lips and one on the left eyebrow. Clinically, the neoplasms were slow growing indurated nodules or plaques. Two of the cases displayed benign features on initial biopsy and their malignant potential could not be established at that stage. On subsequent review, the three neoplasms showed all the characteristic features of microcystic adnexal carcinoma as described by Goldstein et al. and the University of Virginia study. All three patients were treated by surgery in the form of wide excision. They behaved in a highly locally malignant manner with excisions being incomplete in two of the lesions, in spite of taking an adequate margin around the clinically assessable margins. The other recurred after three years in spite of a histologically proven complete excision. Two of the tumours showed infiltration into the underlying muscle with perineural spread. Wider excision in the next stage with frozen section control achieved good clearance and after a five year follow-up period all are symptom free. None of these tumours showed any evidence of distant spread. PMID- 9990793 TI - Ankle fractures in diabetics. AB - Ankle fractures are common and good results are expected. Insulin dependent diabetes mellitus is also common, and long-standing disease is associated with peripheral neuropathy. A trauma unit will inevitably receive patients with both problems. We describe two salutary lessons and suggest how our experience with diabetic neuroarthropathy might be avoided. PMID- 9990794 TI - Gossypiboma revisited: a case report and review of the literature. AB - Gossypiboma (retained surgical sponge) is a rare but preventable occurrence. In this case it presented as a chronic abdominal mass which simulated a primary small bowel tumour. The findings on pelvic ultrasonography were typical for this condition and the role of plain abdominal radiology in the gynaecological patient are highlighted. PMID- 9990795 TI - A non-fatal impalement injury of the thorax. AB - Impalement is an uncommon injury with only occasional reports in the literature. There are even fewer reports of impalement injuries limited to the thorax. We report herein the case of a 24-year-old man who survived impalement injury of the left side of the thorax with a steel rod while working at a construction site. The great vessels of the thorax were spared but the second thoracic vertebra was fractured resulting in complete paralysis of the left lower limb. The precise nature and extent of the injury were determined pre-operatively by computed tomography and aortography. The important principles of surgical management contributing to the successful outcome are described, these being minimal manipulation of the impalement object before and during transport, careful pre operative planning and a multidisciplinary approach. PMID- 9990796 TI - Pancreatic inflammatory tumour: a rare entity in childhood. AB - Pancreatic tumours are rare childhood neoplasms. Inflammatory myofibrohistiocytic tumours (IMTs) represent an uncommon but distinct pathological subgroup that creates diagnostic and therapeutic dilemmas. We report a case of IMT arising from the body and tail of the pancreas in an 8-year-old girl presenting with a mass and abdominal pain. A locally aggressive tumour with no evidence of distant metastasis was encountered at laparotomy and resected. Pathologically, the tumour revealed a mixed inflammatory cell infiltrate with myofibrohistiocytic proliferation. These features can resemble a sarcoma. A review of the literature is provided which emphasises the clinical features, pathological findings, and management strategies for these unusual tumours. Complete surgical excision, aided by radiological surveillance, appears to offer the best guidelines for definitive management. PMID- 9990797 TI - Primary hyperparathyroidism presenting with pathological fracture. AB - Primary hyperparathyroidism (PHPT) is an intriguing condition. Routine automated biochemical screening has made the diagnosis commonplace in developed countries and the disease is diagnosed early in its course when it is often asymptomatic. In developing countries or in recent immigrants from these countries, PHPT is often seen in an advanced stage with bone involvement. Associated dietary deficiencies may alter the biochemical profile and cause a diagnostic dilemma. It is important to include it in the differential diagnosis of pathological fractures. We report three cases of PHPT presenting with pathological fractures and discuss their diagnosis and management. PMID- 9990798 TI - Pre-admission clinic in an orthopaedic department: evaluation over a 6-month period. PMID- 9990799 TI - Extra-articular fractures of the proximal tibial diaphysis: their epidemiology, management and outcome. PMID- 9990800 TI - Adult tonsillectomy: what proportion would accept same day discharge? PMID- 9990801 TI - Gynaecomastia: have Webster's lessons been ignored? PMID- 9990802 TI - Stapler failure in pharyngeal diverticulectomy: a suggested modification in surgical technique. PMID- 9990803 TI - A combined fascia and mesh closure of large incisional hernias. PMID- 9990804 TI - Screening times with image intensifier in orthopaedic trauma surgery. PMID- 9990805 TI - What can and what cannot be inferred from pairwise sequence comparisons? AB - We address questions of identifiability in molecular phylogeny, the art of reconstructing the history of a sample of sequences given just the sequences at the leaves of the phylogenetic tree. Here, the 'history' consists of the tree topology, plus the transition probabilities which define the Markov process of sequence evolution along the branches of the tree. It is assumed that sequences have infinite length, and the pairwise joint distributions of letters at the leaves is taken to be known. We focus on two cases: (1) If the sites of a sequence evolve identically and independently, the topology can be reconstructed, but the one-way edge transition matrices cannot. However, the return-trip transition matrices are reconstructible for every edge, up to conjugation in the case of internal edges. (2) If a rate factor varies from site to site, different topologies may produce identical pairwise joint distributions, even under the same distribution of rate factors. Consequently, identifiability of the topology is lost on the basis of pairwise sequence comparisons, even if the distribution of rate factors is known. The results are discussed in the context of additive measures of phylogenetic distance. PMID- 9990806 TI - Modelling the action of proteinase and inhibitor in tissue invasion. AB - Tissue invasion processes have been receiving considerable attention in recent years. The successful invasion and subsequent implantation of a mammalian trophoblast into maternal uterine tissue is under the control of a self regulating mechanism, as yet not fully determined, which if operating incorrectly can lead to the excessive placental invasion associated with choriocarcinoma or insufficient placental invasion as occurs in the condition of pre-eclampsia. It is hoped that developing an understanding of the mechanisms governing the invasion of trophoblast cells into uterine tissue may lead to an understanding of the control of invasive mechanisms such as those observed in the development of invasive cancers. We have developed here a number of mathematical models in order to gain a better understanding of the role of proteinase and inhibitors in the context of trophoblast invasion. The models, which may be extended to other tissue invasion mechanisms, are based upon a series of proposed experiments involving blastocysts invading reconstituted basement membrane (Matrigel) allowing the quantification of the proteinase-Matrigel and proteinase-inhibitor interactions. PMID- 9990807 TI - Phylogenetic analysis of nucleotide sequences: an algebraic approach. AB - In a previous paper Schmidt and Mueller [Bull. Math. Biosci. 58 (3) (1996) 449.] proposed a new method for calculating phylogenetic trees from dichotomous (present/absent) properties of the taxonomic units. The proposed method is based on a specified distance measure quantifying the phylogenetic information content of the selected properties with respect to the joint evolutionary history. Formally, the method can be applied to arbitrary property patterns and is not based on restricting evolutionary models and optimization principles looking forward in evolutionary time. Instead, its theoretical foundation is the retrospective postulate that properties which are present in any two (closely related) taxa were also present in their most recent common ancestor. The reliability of the derived trees depends essentially on the phylogenetic relevance of the chosen properties. To apply this method to related nucleotide sequences I have defined a set of biologically meaningful nucleotide properties which separate and evaluate the different substitution events. The proposed algorithm provides additive trees and needs no numerical constraints to avoid negative branch lengths or any other meaningless result. In a series of applications the method has been tested and compared with the outcomes of other established tree reconstruction methods. For demonstration, I report and discuss the results of the reanalysis of two families of genomic sequences. Here and in a series of further applications I obtained trees which are biologically acceptable and in good coincidence with the published trees. Thus, it can be concluded that the proposed method will be a useful alternative for the study of phylogenetic relationships. PMID- 9990808 TI - Comparison of the effects of vasectomy and experimental cryptorchidism in rats: II. Epididymal histology. AB - Vasectomy is a male contraception method that its side effects and reversibility rate are still controversial. Effects of vasectomy on epididymal morphology and function, which plays a crucial role in sperm maturation and storage, have not yet fully described. Therefore the present study was planned to find out the effects of vasectomy on epididymal structure, and comparisons of these effects were also made with the effects of a persistent infertility model, experimental cryptorchidism. To do this, 15 male Swiss albino rats were divided into 3 groups. While 5 animals were sham-operated, the rest were undergone either vasectomy (5 rats) or experimental cryptorchidism (5 rats) procedures. Epididymal tissue samples were collected prepared for light microscopy. Tissue sections were stained using appropriate staining techniques and evaluated under the light microscope. While there were distinct alterations in the epididymal morphology following experimental cryptorchidism, vasectomized rat epididymal features seemed similar to those seen in the sham-operated group. In conclusion, it could be suggested that the vasectomy might be a convenient method for male contraception. PMID- 9990809 TI - Examination of nerve distribution to masticatory muscles using a silicone permeation technique. AB - The detailed anatomical distribution of nerves throughout the human body has generally been studied by dissection of fixed cadavers in liquid. In this traditional method, it is difficult to maintain the position of nerves on their respective muscles. It is also difficult to keep the distributed form of the nerves. To understand the morphology of nerves, it is essential to determine their location and distribution precisely. In this study the masseter muscle was removed from a cadaver after fixation with formalin. The muscle was then permeated with silicone using the following procedure. The muscle fixed by 10% formalin was dehydrated with alcohol. After dehydration, alcohol was replaced with methylene chloride. The sample was permeated by silicone in a permeater. Following dissection, enamel was applied to the nerve by hand to fix its position. This new permeation method provided excellent localization of nerves innervating the muscle and has the added advantage of providing a three dimensional structure of neural anatomy similar to the casting procedures used to visualize blood vessels. PMID- 9990810 TI - Electron microscopic study of intercalated duct cells in the chicken pancreatic islet and effects of tolbutamide administration. AB - Intercalated duct cells are present in the alpha and beta islets of chicken. The intercalated duct cells adhere to each other via intercellular junctional complexes at the apical side, projecting many microvilli and a few cilia into the lumen. They also extend slender cytoplasmic processes between the islet endocrine cells. These intercalated cells appear to have a stellate form, and to wrap their cytoplasm around endocrine cells. Administration of tolbutamide led to increased electron density in the cytoplasm of intercalated duct cells. Lysosomes are present in these cells in various numbers and sizes and tend to increase with time after administration of tolbutamide. These observations suggested that the intercalated ducts not only pass through the islet, but also play a role in supplying islet cells. PMID- 9990811 TI - Sexual dimorphism in the tooth crown dimensions of the second deciduous and first permanent molars of Taiwan Chinese. AB - Sexual dimorphism in the crown components in the second deciduous molar (dm2) and the first permanent molar (M1) of the dental casts taken from Chinese living in Kaohsiung (Taiwan) was investigated. Mesiodistal and buccolingual crown diameters, and 4 main-cusp sizes in the maxillary molars and mesiodistal diameters of the trigonid and talonid in the mandibular molars were measured using a digital caliper (0.01 mm). Percentage sexual differences were calculated. With the exception of trigonid mesiodistal diameters, the mean values of males were larger than females. In both of dm2 and M1 the mean values of the trigonid mesiodistal diameters were slightly larger in females than in males, but the differences were not significant. Percentage sexual dimorphism was smaller in the mesiodistal diameters than in the buccolingual in both dm2 and M1. The crown components showed larger sexual difference in dm2 than in M1, while in the maxilla the external crown size showed larger sexual difference in M1 than in dm2. The buccal cusps showed larger sexual difference than the lingual in the maxillary molars and the talonid showed larger sexual difference than the trigonid in the mandibular. Sexual dimorphism of dm2 and M1 in their crown components displayed similar pattern, although the different degree was noted. This result is thought to relate to the fact these molars belong to the first dentition embryologically. PMID- 9990812 TI - Light and electron microscopic examination of exocrine pancreas using zinc iodide osmium tetroxide technique. AB - Zinc iodide-osmium tetroxide (ZIO) fixation/staining technique is a metallophilic technique which has been used for the examination of various tissues and cell types. We examined the ZIO (+) cell types in rat exocrine pancreas to obtain further evidence for the significance of the reaction. Among mostly non-reactive pancreatic acinar cells there were ZIO (+) acinar cells of varying staining intensity. Zymogenic granules and centroacinar cells were completely non reactive. Our electron microscopic findings support the view that the reactivity of the technique used is cell specific but not cell type or organelle specific. PMID- 9990813 TI - Morphology of the tracheobronchial tree and the route of the pulmonary artery in the fetal minke whale (Balaenoptera acutorostrata). AB - Molecular and statistical studies support the close phylogenetic relation between Cetacea and Artiodactyla. The presence of the tracheal bronchus has been pointed out as one of the common traits between only these groups. Nakakuki (1980) has investigated the mammalian tracheobronchial trees in 50 species based on his new nomenclature, and his study has consequently demonstrated the above-mentioned indication. Therefore, comparative anatomy of the tracheobronchial tree based on the nomenclature seems to be useful for investigations of the cetacean phylogeny. Three pairs of fetal lungs of the minke whale (Balaenoptera acutorostrata) were supplied from the Institute of Cetacean Research, Tokyo (1991) to observe their tracheobronchial trees and the ramification of the pulmonary artery. The fetal tracheobronchial tree consisted of one tracheal, four lateral, four dorsal and one medial secondary bronchi in the right lung, and five or six lateral and four or five dorsal secondary bronchi in the left, using the new nomenclature. The right pulmonary artery crossed the right axial bronchus from the ventral side to the dorsal over the third lateral bronchus. The tracheal bronchus in the fetal minke whale seems to belong to the type II of Nakakuki's nomenclature, and this type is seen in one species of the river dolphins. The other conspicuous traits of the fetal lungs are the defect of the second lateral broncus and the route of the pulmonary artery in the right side. This route is very different from that of many other mammals. PMID- 9990814 TI - An anomalous ascending cervical artery. AB - During gross anatomy dissection of the neck region, an anatomical variation of the ascending cervical artery was detected. Normally this artery is a branch of the inferior thyroid artery, which is a branch of the thyrocervical trunk. In our case, we found that the ascending cervical artery emerged from the superficial cervical artery, nearly 1 cm. lateral to the origin of this artery from the thyrocervical trunk. PMID- 9990815 TI - [Detection of human papillomavirus infection by the nucleic acid hybridization method (a multicenter study)]. AB - The human papillomaviruses (HPV) are regarded as one of the important agents of cervical carcinoma. A multicentre study was organized to determine the prevalence of HPV in the fertile female population in Hungary. Parallel with the clinical sample collection, a questionnaire interview was performed to acquire data on the life style, socioeconomic status, sexual practice, etc. 1200 women were examined colposcopically and cervix samples were collected for cytology and the detection of HPV DNA. 17.4% of the samples were HPV-infected. 3.9% of the patients had acquired low-risk, and 10.1% 10.2% high-risk HPV types; 3.4% of the women were at the same time infected with both low-risk and high-risk HPV types. Simultaneously performance of cytology and the HPV hybrid capture assay contribute to recognise and treat the precancerous status and risk factors. PMID- 9990816 TI - [Eradication of Helicobacter pylori in peptic ulcer patients]. AB - The aim of this study was to compare in an open trial the efficacy of 2 x 500 mg clarithromycin + 2 x 1000 mg amoxicillin + 40 mg pantoprazole/day given for 7 days (I. group, 48 cases), with that of 2 x 500 mg clarithromycin + 2 x 400 mg ranitidine bismuth citrate/day given for 14 days (II. group, 51 cases). The diagnosis of peptic ulcer was established endoscopically. HP infection was confirmed the modified Giemsa stain and rapid urease test. After eradication all patients were given 2 x 150 mg ranitidine for one month. Controls were performed 4-6 weeks after eradication. Peptic ulcer healing was proven in the group I in 93.0% and in the group II in 91.6% (p > 0.05). On intention-to-treat basis, HP was eradicated in 80.3% (confidence interval, CI: 73-92.7%) in the I. and 80.3% (confidence interval: 76-95%) in the II. group (p > 0.05). Per protocol analysis revealed eradication rates of 88.3% (CI: 81-97.6%) and 85.4% (CI: 80-97%) (p > 0.05). Side effects were recorded in 9.5% and 14.5% of the cases. Both regimens were equally effective in the eradication of HP and healing of peptic ulcers. PMID- 9990817 TI - [Screening methods in genetic diagnosis of hereditary protein C deficiency]. AB - Genomic analysis and detailed blood coagulation examinations of 22 family members of 18 families with repeatedly low protein C activity have been performed. Blood coagulation examinations: INR, fibrinogen, plasminogen, alpha-2-antiplasmin, lupus anticoagulant, APC resistance test, protein C activity and antigen, protein S activity and antithrombin activity. Genetic examinations: the presence of FII G20210A alle and FV:Q506 Leiden mutation were examined and for the mutation screening in the protein C gene combination of polymerase chain reaction (PCR) with denaturing gradient gelelectrophoresis (DGGE) or with single-strand conformation polymorphism (SSCP) analysis has been performed. The amplified DNA fragments with aberrant migration during DGGE and SSCP analysis were sequenced. Nine family members of seven families were identified carrying mutations in the protein C gene: one nonsense mutation in exon VII (Arg 157-Stop), two types of missense mutations in four patients in exon IXA (230 Arg-Lys, 254 Thr-Ile, the latter is a new mutation, Protein C Pecs), one missense mutation in two patients in exon IXB (325 Val-Ala), one missense mutation in exon IXC (359 Asp-Asn) and a rare frameshift deletion in exon IXC (364 Met-Trp, 378 Stop). Nine families were evaluated carrying no mutation in their protein C gene, but other genetic or blood coagulation disturbances have been identified, eight of them had borderline decrease in their protein C activity (60-70%). The presence of FV:Q506 mutation could be diagnosed in eight families (in 3 cases homozygous, in 5 cases heterozygous form), among them combination of the defects could be proved in three of the eight families: FV:Q506 Leiden mutation with antiphospholipoid antibodies in 2 families and the presence of Leiden mutation with prothrombin gene mutation in 1 family. Protein S deficiency in combination with prothrombin gene mutation has been identified in 1 family. There were 2 families where no genetic or blood coagulation alterations could be detected in the background of the repeatedly low protein C activity. Large deletions or insertions which are not detectable by our screening methods could not be excluded in these families and therefore sequencing of the total protein C gene had been performed with negative results. According to the literature and our experience the screening methods that were administered in this study are suitable for the detection of mutations in the protein C gene. PMID- 9990818 TI - [The role of myocardial apoptosis in the development of heart failure]. AB - Heart failure can result from a variety of causes, including volume or pressure overload and contractile disturbances of the myocardium. Loss of myocytes is an important mechanism in the development of cardiac failure. In general, myocyte death resulting in progressive deterioration of myocardial function is attributed to necrosis, but recently the involvement of programmed cell death (mainly apoptosis) has been suggested. The authors review the possible role of myocardial apoptosis in developing of heart failure. Subcellular genetic regulatory processes as well as the pharmacological susceptibility of programmed cell death are also discussed. In heart failure, significant amount of cardiac myocytes undergoes apoptosis, that unlike necrosis can be prevented. Specific inhibition of this process could mean a considerable part of cardioprotection after thorough understanding of the underlying cellular mechanisms. PMID- 9990819 TI - Kohut and Glover. The role of subjectivity in psychoanalytic theory and controversy. AB - The role of conflictual elements in the genesis of a new theory and in relation to the use of theory in a psychoanalytic controversy will be explored in two "case" studies. In the first, a close reading of Kohut's "The Two Analyses of Mr. Z" and in the second, a detailed examination of Glover's shifting allegiances toward Kleinian theory will reflect the role of transference and of idealization as powerful motivating elements. PMID- 9990820 TI - Erik Erikson's dream specimen paper. A classic revisited. AB - This paper offers an overview of Erik Erikson's contribution to psychoanalysis, contrasting the humanistic perspective from which he viewed psychoanalysis with the biological perspective adopted by Heinz Hartmann. The vehicle for this comparison and for the explication of Erikson's extension of the work of Freud and Hartmann is Erikson's analysis of Freud's Irma dream, as presented in his Dream Specimen paper. I hope to show that: (1) Erikson's analysis of Freud's Irma dream provides a masterful illustration of the richness and complexity of past and current life themes and conflicts that inform the dreamer's construction of the manifest surface of the dream. (2) Erikson's examination of the relationship between the manifest content of the dream and the current life context of the dreamer leads him to propose a connection between trauma and the origins of the dream. This view complements Freud's discovery of the instinctual motivation for dreaming and anticipates subsequent discoveries concerning the role of dreams and REM sleep in defensive ego functioning and adaptation. (3) The Dream Specimen paper presents readers with a humanistic ego psychology that rests upon--but is subtly different from--the work of Hartmann and the other biologically oriented analysts of his day. In this sense, Erikson's paper is an elegant "specimen" of ego psychology carried to its most creative heights. PMID- 9990821 TI - Evelyn K. Oremland's contributions to the child life profession. AB - Evelyn K. Oremland, Ph.D., founded the first college-based Child Life Program on the West Coast. A pioneer in child life, in her twenty years at Mills College, Oakland, California, she developed a graduate curriculum to create the child life profession. Through her tireless activities in the international organization, Association for the Care of Children's Health (ACCH), and her co-chairing the Educational Committee of the Child Life Council, she helped establish standards for the child life specialist certification. Around the world, her teaching, research, and writing have helped protect the emotional development of sick children. She is best remembered as a devoted and beloved teacher. Graduates from her program now occupy many senior administrative positions in child life in the United States and in Europe. PMID- 9990822 TI - The importance of play in adulthood. An interview with Joan M. Erikson. Interview by Daniel Benveniste. AB - Joan M. Erikson (1902-1997) was an artist, a writer, a mother, and the wife and collaborator of Erik H. Erikson (1902-1994), one of the most important and influential psychoanalysts in the world. The following is an edited dialogue on one of her favorite topics--The Importance of Play in Adulthood. It features her thoughts on the subject and reminiscences of the ways she played throughout her life. She muses on play in relation to humor, fun, the role of the fool, and more. The article was a project undertaken in the spirit of play and it will hopefully evoke further playful musings in the minds of readers. PMID- 9990823 TI - Play and the metaphors of the body. AB - Symptoms and the sense of reality are built out of the reified metaphors of the body. In clinical psychology we deal less with the frozen events of "objective reality" and more with the fluid experiences of a subjectivity. Metaphor is the language of experience. In this paper I will cover briefly a wide range of material including children's play configurations, children's fantasy narratives, libido development, the symbolic function, the role of metaphor in the construction of a world view, and the recognition of metaphor as an organizing concept in psychoanalytic theory and technique. In doing so, I will illustrate the relationship between play and the metaphors of the body. PMID- 9990824 TI - Play, dreams, and creativity. AB - Viewed ontogenetically, creating, dreaming, and playing are a variant of object relatedness. It is suggested that in recapitulating the ontogenetic sequence, creating, dreaming, and playing each as a process initiates by de-differentiation to primal union, evolves into transitional functioning, and consummates in tertiary cognitive discourse. The products of the triad--the created object, the dream, and play--are viewed as synergistic psychodynamic composites of topical, personal, and arche-typical imperatives. Creating, dreaming, and playing are easily overburdened by events, becoming stereotypical and repetitious. Nowhere is this more clearly seen than in the play of chronically ill, hospitalized children. It is suggested that with development generally, playing is replaced by formalized games; only dreaming continues as the vestige of early creative abilities. PMID- 9990826 TI - Beyond play and playfulness. AB - The evolution of play to playfulness over time establishes developmental foundations that are of central importance throughout life. Freud believed that play is at its richest and most adaptive during the oedipal phase; others have taken issue with Freud's view that play has its place mainly in childhood and is given up in adulthood. This paper emphasizes the central importance of playfulness throughout life. In formulating the boundaries of play, it utilizes the observations and comments of experts in the field. PMID- 9990827 TI - A developmental line of time sense. In late adulthood and throughout the life cycle. AB - This is the sixth and final paper in a series by the author on the normative, intrapsychic experience of time throughout the life cycle. Time sense is understood to be shaped by the primary forces that influence development at all points in the life cycle: an amalgam of past temporal conceptualizations, current developmental themes, and environmental influences. After a summary of the development of time sense in infancy, childhood, adolescence, and young and middle adulthood, this paper focuses on the experience of time after age sixty. The effect of death awareness and death anticipation, life reviews, reminiscence, and object relationships is discussed, as is the emergence of late-life generativity and wisdom. These concepts are illustrated by clinical material from the analysis of seventy-year-old woman. PMID- 9990825 TI - Play and therapeutic action. Multiple perspectives. AB - Children's play that goes unanalyzed within a psychoanalysis, yet leads to therapeutic change, is contrasted with interpreted play that leads to conscious insight. The therapeutic and development facilitating effects of unanalyzed play suggest that substantial analytic work goes on unconsciously. Technical issues arise, therefore, if play is conceptualized as a therapeutic force in its own right. Developmental considerations and inhibitions in play become greater considerations in analytic technique. Two clinical vignettes from the analyses of latency-age girl and boy are presented to illustrate unanalyzed play as an agent in development and mastery of anxieties. PMID- 9990828 TI - The etiology of narcissistic personality disorder. AB - This paper presents a view of the etiology of narcissistic personality disorder which, while not new, is at variance with the commonly held position that this disorder is the outcome of the insufficient gratification of the normal narcissistic needs of infancy and childhood. The contrary thesis is presented: that narcissistic personality disorder is the outcome of narcissistic overgratification during childhood. A fixation to this overgratification interferes with the normal maturation and integration of the superego, leading to difficulties in self-esteem regulation and to a tendency to massive externalization. Clinical material is presented to support this view. PMID- 9990829 TI - A psychoanalytic study of aggression. AB - Eleven participants carried out a study of aggression by utilizing clinical data from the analyses of patients who manifested significant problems in the management of aggression. The purpose of the study was to increase understanding of the intrapsychic factors that determine the nature and intensity of aggressive tendencies, the place they occupy in the psychic economy, their patterns of expression, and the extrapsychic factors that trigger them. The findings of the study indicate, first, that aggression is multiply determined by developmental, genetic (experiential), and dynamic variables; second, that each cluster of variables affects the nature, intensity, and expression of aggression in a fairly specific way; third, the importance of aggression in the psychic economy is proportional to the extent to which it is overdetermined. The successful analysis of aggressive individuals depends not solely on interpretation and insight, but on the relationship to the analyst as new parent who does not threaten and prohibit. The relationship to the analyst permits developmental change, particularly the ability to organize, structure, and control aggression. As a result, it need not be expressed destructively, but may be placed in the service of constructive thought and action. PMID- 9990830 TI - We all need our tails to lean on. An analysis of a latency-age girl with a gender identity disorder. AB - This essay reviews current theories of gender identity disorders, with particular reference to the etiology of the problem in girls. The analysis of a latency-age girl with a serious cross-gender identity disorder is presented in detail. The case material illustrates the complex relationships among this girl's fantasies about her adoption, her ambivalent attachments to her adoptive parents and brother, her pet rats, and about herself as a boy. In the analytic work, the real and transferential connections to the analysts were explored, which enabled the patient to reenact the traumatic derailments in her early attachments, to begin to mourn her losses, and to move to a more feminine identification. PMID- 9990831 TI - The use of dream analysis in the treatment of a nine-year-old obsessional boy. AB - In children, as in adults, dreams offer a direct access to the unconscious. The analysis of dreams in the psychoanalytic treatment of children is, however, a neglected area. The work that a 9-year-old boy did with his dreams during the course of his two-and-a-half-year analysis is presented to demonstrate how helpful dream analysis can be in elucidating conflict and defense in the child patient. With children, the responsibility for inquiring about dreams rests with the analyst. The associations a child has to his or her dreams are as useful as an adult's. PMID- 9990832 TI - Conflict and compromise in gender identity formation. A longitudinal study. AB - The aims of this paper are twofold. The first aim is to show the complexity of the determinants leading to gender identity formation via the longitudinal study of one female research subject over 33 years. Focus is on the origins, meanings and functions of masculine character traits accrued at each phase of development. The second aim is to show that character formation begins early in the second year of life and that early patterns have a certain continuity with adult character despite reorganizations of the oedipal phase and subsequent contributions from each phase of development. Discussion focuses on the complicated nature of female gender identity formation. PMID- 9990833 TI - Croup, a disorder of the anal phase of development. A contribution to our understanding of the psychosexual development of the larynx. AB - A brief history of croup is presented. The forms of croup under examination are defined with emotional factors at one end of a continuum and viral and traumatic factors at the other. The complexity of the disorder and its peculiar clinical characteristics are explained. Some of these characteristics are: (1) the predominant 1-3-year age range, which corresponds to the anal stage of development; (2) the relief afforded by vomiting; (3) the occurrence of attacks at night and during sleep, (4) the relative dryness of the cough and its harsh metallic quality; (5) the frequent presence of a ticklish, irritating sensation in the throat; and (6) the presence of edema and/or laryngospasm. Three case vignettes are presented. These cases support a previously developed theory concerning the impulses and defenses underlying the croup attack. Croup is seen as a fixation at the oral level with a regression to that level in the face of conflicts of the anal or sometimes the oedipal stage. The psychosexual development of the larynx is discussed. PMID- 9990834 TI - Parents of autistic children. Some thoughts about trauma, dislocation, and tragedy. AB - People who suffer unexpected trauma often go through periods of intense dislocation, which resolve into a new sense of self-organization, marked by a distinct sense of tragedy. Parents of autistic children are given as an example of this phenomenon. Dislocation is described as not just part of the mourning process but as the result of the disturbance of both the internal and external components that maintain ego autonomy. Some suggestions are given for working with traumatized parents to help them reorient themselves within this dislocation and to foster and preserve their sense of being "good enough" parents. PMID- 9990835 TI - A parapraxis in Hamlet. A note on the aesthetic genius of William Shakespeare. AB - Shakespeare has placed a parapraxis in Hamlet's mouth in the soliloquy in Act I. Hamlet says, "But two months dead, nay not so much not two." The slip attributed to Hamlet is of course no slip at all when seen as an aesthetic contrivance of the bard's to suggest the tension between warring aspects of Hamlet's psychology. I argue that Shakespeare's artistic methodology, his aesthetic sleight of hand, so to speak, which layers this complex drama with meanings concealing other meanings, supports Freud's notion that an unconscious latent oedipal drama underlies the whole manifest content, imbuing it with subtle but substantial dramatic tension. The slip of the tongue is not only a window into the unconscious of Hamlet that sheds light on the hero's Oedipus complex and the complexities of his attempted resolutions, it is also an example of Shakespeare's aesthetic subtlety at its most refined. PMID- 9990836 TI - Dyslexia and self-control. An ego psychoanalytic perspective. AB - Dyslexia and the self-control problems that frequently accompany it are viewed from an ego psychoanalytic perspective. Dyslexia is conceptualized as resulting from an ego deficit in language processing; this deficit is seen as contributing to the ADHD-type symptoms often seen in dyslexic children. Lacking certain crucial components of linguistic competence, the dyslexic child is therefore also lacking a basic tool of impulse control. As a result, this child may exhibit a type of language deficit based impulsivity that has dynamic characteristics which are diagnostically significant. In addition, the ego deficit associated with dyslexia affects and interacts with unfolding drives, especially during the oedipal phase; unlike the more normal child, whose newly ascendant language skills help to inhibit oedipal fantasies and impulses, the dyslexic youngster is prone to a marked intensification of oedipal concerns, especially as these interact with actual experiences of failure. The treatment implications of these issues are discussed. PMID- 9990837 TI - The splintered holding environment and the vulnerable ego. A case study. AB - This paper describes the developmental dilemmas of children in long-term foster care whose permanent placement is delayed for years. Developmental theory and clinical research postulate the psychological risks to children who face the continuous threat of primary object loss. The detailed account of Matthew's case illustrates the effects of early neglect, abuse, and multiple separations on ego development. Matthew was removed from his birth mother at thirteen months but was not adopted by his foster mother until he was seven years old. He entered therapy when he was four. The clinical material reveals not only his strong will for survival but also his gradual internalization of the fear of primary object loss, his extreme narcissistic vulnerability, and his hypervigilance concerning danger, abandonment, and annihilation. He had great difficulty controlling his impulses. With some technical modifications, treatment enabled Matthew to strengthen his capacity for object relatedness, self-reflection, and learning. The paper demonstrates how important it is for social welfare agencies and the courts to be more cognizant of developmental theory and to recognize the need for earlier permanent placement determinations. PMID- 9990838 TI - Boundaries of self and subject. The aesthetic consequences of engulfment and separation anxiety in two artists. AB - The paper considers the efforts of two artist patients--one productive and the other not--to manage engulfment and separation anxiety through manipulations of virtual and literal spaces. The patients assumed characteristic emotional distances from their objects, subjects, products, audiences, and culture. More concretely, they developed artistic styles that, through formal structure and narrative content, signified a compromise between isolation and merger. Further investigation revealed that the productive patient's mother suffered a protracted postpartum depression that estranged her emotionally and physically from the patient in infancy. The tension between early maternal deprivation and later reaction-formed intrusiveness promoted the patient's aesthetic compromise between communication and concealment, permitting successful delivery of fantasy material. Although the unproductive patient portrayed repellent scenes which alienated her audience, she curiously never attempted stylistic corrections. Her press for merger was countered by a dread of contact conditioned by paternal abuse. Further exploration suggested that her artworks were not selfobjects, but rather close relations competing with her for audience attention. PMID- 9990839 TI - The effect of mutations on peptide models of the DNA binding helix of p53: evidence for a correlation between structure and tumorigenesis. AB - The tumor suppresser protein p53 has been called the "guardian of the genome." DNA damage induces p53 to either halt the cell cycle, allowing for repair, or initiate apoptosis. P53 is mutated in over 50% of human tumors and it has been proposed that many tumorigenic mutations are deleterious to p53 because they induce local unfolding. To explore this hypothesis, peptide models have been developed to study tumorigenic mutations in the H2 helix of the p53 core domain. This helix is rich with charged residues and is a key component of the DNA binding region. A 16-residue peptide corresponding to the H2 wild-type sequence extended with an Ala-rich C-terminus was synthesized and studied by 1H-nmr (500 MHz) and CD. The nmr studies demonstrate that this peptide adopts helical structure in solution. Six additional peptides corresponding to subtle tumorigenic mutations were synthesized and CD was used to assess the relative stability of these "mutant analogues." All six mutations studied are destabilizing relative to the wild type, with delta delta G values in the range of 0.26 to 1.35 kcal mol-1. Surprisingly, substitution of Asp 281 with Ala resulted in a peptide with the greatest destabilization even though Ala possesses the largest helix propensity of the common 20 amino acids. Because this helix appears to be stabilized mainly by local electrostatics, we conclude that its structure is susceptible to even the most conservative mutations. These results provide support for the hypothesis that tumorigenic mutations induce local unfolding of p53. PMID- 9990840 TI - Phosphorylation stabilizes the N-termini of alpha-helices. AB - The role of phosphorylation in stabilizing the N-termini of alpha-helices is examined using computer simulations of model peptides. The models comprise either a phosphorylated or unphosphorylated serine at the helix N-terminus, followed by nine alanines. Monte Carlo/stochastic Dynamics simulations were performed on the model helices. The simulations revealed a distinct stabilization of the helical conformation at the N-terminus after phosphorylation. The stabilization was attributable to favorable electrostatic interactions between the phosphate and the helix backbone. However, direct helix capping by the phosphorylated sidechain was not observed. The results of the calculations are consistent with experimental evidence on the stabilization of helices by phosphates and other anions. PMID- 9990841 TI - Smoluchowski dynamics of the vnd/NK-2 homeodomain from Drosophila melanogaster: first-order mode-coupling approximation. AB - This work is the first in a series devoted to applying mode coupling diffusion theory to the derivation of local dynamics properties of proteins in solution. The first-order mode-coupling approximation, or optimized Rouse-Zimm local dynamics (ORZLD), is applied here to derive the rotational dynamics of the bonds and compare the calculated with the experimental nmr 15N spin-lattice relaxation time behavior of the vnd/NK-2 homeodomain from Drosophila melanogaster. The starting point for the calculations is the experimental three-dimensional structure of the homeodomain determined by multidimensional nmr spectroscopy. The results of the computations are compared with experimentally measured 15N spin lattice relaxation times T1, at 34.5 and 60.8 MHz, to check the first-order approximation. To estimate the relative importance of internal and overall rotation, both rigid and fluctuating dynamic models are examined, with fluctuations evaluated using molecular dynamics (MD) simulations. The correlation times for the fundamental bond vector time correlation function and for the second-order bond orientational TCF are obtained as a function of the residue number for vnd/NK-2. The stability of the corresponding local dynamics pattern for the fluctuating structure as a function of the length of the MD trajectory is presented. Diffusive dynamics, which is essentially free of model parameters even at first order in the mode-coupling diffusion approach, confirm that local dynamics of proteins can be described in terms of rotational diffusion of a fluctuating quasi-rigid structure. The comparison with the nmr data shows that the first-order mode coupling diffusion approximation accounts for the correct order of magnitude of the results and of important qualitative aspects of the data sensitive to conformational changes. Indications are obtained from this study to efficiently extend the theory to higher order in the mode-coupling expansion. These results demonstrate the promise of the mode-coupling approach, where the local dynamics of proteins is described in terms of rotational diffusion of a fluctuating quasi-rigid structure, to analyze nmr spin-lattice relaxation behavior. PMID- 9990842 TI - Physicochemical properties of arterial elastin and its associated glycoproteins. AB - Microfibrillar glycoproteins are a significant component of vascular elastic tissue, but little is known about their contribution to vascular physiology and pathology. We have investigated some physicochemical properties of the glycoproteins that may be pertinent to these roles. Because of the difficulty in isolating intact glycoproteins in a form and quantity suitable for physicochemical examination, we based our analysis on a comparison of the properties of porcine thoracic aorta and pulmonary artery extracted with GuHCl and collagenase (preparation GC) and after further treatment with dithioerythritol to remove glycoproteins (preparation GC/DTE). Amino acid analysis showed that GC/DTE had the amino acid composition of pure elastin while GC contained a higher proportion of polar amino acids, particularly in the aortic preparation. GC stained with alcian blue, particularly in the intimal region, but GC/DTE did not. GC had a higher water content and a slower viscoelastic response and the circumferential elastic modulus was approximately 50% lower (whether expressed in terms of sample weight or elastin content). Clearly, therefore, the microfibrils do not stiffen the network and may prevent the alignment of elastin fibers in the circumferential direction. Their effect on hydration may arise either because they impose mechanical constraints on the geometry of the network or because they modify the inter- and intramolecular hydrophobic or electrostatic interactions that influence the tissue organization and hydration. Molecular probe measurements of the intrafibrillar pore structure using radiolabeled and fluorescent probes showed that removal of the microfibrils caused a slight decrease in the extrafibrillar water space and a larger decrease in the intrafibrillar water space. Sucrose, a small probe molecule, was able to penetrate most of the intrafibrillar water space when microfibrils were present but was virtually excluded when they were not. Potentiometric titration and radiotracer assays of ion binding both showed that the microfibrils contribute a considerable negative charge (-9 mumoles/g wet tissue in the aortic preparation and -16 mumoles/g wet weight in the pulmonary artery) and increase calcium binding by approximately 30%. PMID- 9990843 TI - On the bipolarity of positive and negative affect. AB - Is positive affect (PA) the bipolar opposite of, or is it independent of, negative affect (NA)? Previous analyses of this vexing question have generally labored under the false assumption that bipolarity predicts an invariant latent correlation between PA and NA. The predicted correlation varies with time frame, response format, and items selected to define PA and NA. The observed correlation also varies with errors inherent in measurement. When the actual predictions of a bipolar model are considered and error is taken into account, there is little evidence for independence of what were traditionally thought opposites. Bipolarity provides a parsimonious fit to existing data. PMID- 9990844 TI - The savant syndrome: intellectual impairment and exceptional skill. AB - Occasionally, people with developmental disability display skills at a level inconsistent with their general intellectual functioning, so-called "savant" behavior. Studies of savant behavior are reviewed to determine their relevance to notions about the importance of general intellective functions in the development of exceptional skill. It is concluded that (a) the skill exhibited by savants shares many characteristics with that in people without disability, (b) the skill is usually accompanied by normative levels of performance on at least some subtests of standardized measures of cognitive achievement, and (c) it is unclear whether savants have distinctive cognitive strengths or motivational dispositions, though their relative prevalence among people with certain kinds of disability suggests predisposing constraints. The author proposes that these skills typically reflect highly elaborated preconceptual representational systems. PMID- 9990845 TI - The impact of attitudes on memory: an affair to remember. AB - Many theories of the effects of attitudes on memory for attitude-relevant information would predict that attitudinally congenial information should be more memorable than uncongenial information. Yet, this meta-analysis showed that this congeniality effect is inconsistent across the experiments in this research literature and small when these effects are aggregated. The tendency of the congeniality effect to decrease over the years spanned by this literature appeared to reflect the weaker methods used in the earlier studies. The effect was stronger in 2 kinds of earlier experiments that may be tinged with artifact: those in which the coding of recall measures was not known to be blind and those that used recognition measures that were not corrected for bias. Nonetheless, several additional characteristics of the studies moderated the congeniality effect and suggested that both attitude structure and motivation to process attitude-relevant information are relevant to understanding the conditions under which people have superior memory for attitudinally congenial or uncongenial information. PMID- 9990846 TI - Psychosocial correlates of heterosexual condom use: a meta-analysis. AB - Despite increasing incidence of HIV/AIDS, there has been no systematic review of correlates of condom use among heterosexual samples. To rectify this, the present study used meta-analysis to quantify the relationship between psychosocial variables and self-reported condom use. Six hundred sixty correlations distributed across 44 variables were derived from 121 empirical studies. Variables were organized in terms of the labeling, commitment, and enactment stages of the AIDS Risk Reduction Model (Catania, Kegeles, & Coates, 1990). Findings showed that demographic, personality, and labeling stage variables had small average correlations with condom use. Commitment and enactment stage variables fared better, with attitudes toward condoms, behavioral intentions, and communication about condoms being the most important predictors. Overall, findings support a social psychological model of condom use highlighting the importance of behavior-specific cognitions, social interaction, and preparatory behaviors rather than knowledge and beliefs about the threat of infection. PMID- 9990847 TI - Does competition enhance or inhibit motor performance: a meta-analysis. AB - A meta-analysis was conducted on the relative impact of cooperative, competitive, and individualistic efforts on motor skills performance. Competition was divided into 3 groups: zero sum, appropriate, and unclear. The motor skills tasks were divided into means-interdependent and means-independent tasks. The dependent variables were achievement-performance, interpersonal attraction, social support, and self-esteem. A total of 64 studies met the criteria for inclusion. Effects sizes were computed, and confidence intervals were used to determine their significance. A fail-safe sample size was computed to determine how many additional studies were needed to change the significance of the results. Cooperation resulted in higher achievement for means-interdependent tasks in zero sum competition, unclear competition, and individualistic efforts, and it promoted higher achievement for means-independent tasks for unclear competition and individualistic efforts. For all comparisons, cooperation resulted in greater interpersonal attraction, social support, and self-esteem. PMID- 9990848 TI - Event-related functional MRI: implications for cognitive psychology. AB - Functional magnetic resonance imaging (fMRI) has rapidly emerged as a powerful technique in cognitive neuroscience. We describe and critique a new class of imaging experimental designs called event-related fMRI that exploit the temporal resolution of fMRI by modeling fMRI signal changes associated with behavioral trials as opposed to blocks of behavioral trials. Advantages of this method over block designs include the ability to (a) randomize trial presentations, (b) test for functional correlates of behavioral measures with greater power, (c) directly examine the neural correlates of temporally dissociable components of behavioral trials (e.g., the delay period of a working memory task), and (d) test for differences in the onset time of neural activity evoked by different trial types. Consequently, event-related fMRI has the potential to address a number of cognitive psychology questions with a degree of inferential and statistical power not previously available. PMID- 9990849 TI - IAP family proteins--suppressors of apoptosis. PMID- 9990850 TI - Core promoter elements can regulate transcription on a separate chromosome in trans. AB - Transvection can cause the expression of a gene to be sensitive to the proximity of a homolog. It can account for many cases of intragenic complementation at the Drosophila yellow gene, where one mode of transvection involves the action of enhancers in trans on a promoter present on a separate chromosome. Our goal was to identify cis-acting elements that regulate the trans action of enhancers. Using gene replacement, we altered two core promoter elements at yellow and tested the resulting alleles for their ability to support transvection. We found that the TATA box and initiator element can regulate transvection. PMID- 9990851 TI - Distinct transcriptional regulatory mechanisms underlie left-right asymmetric expression of lefty-1 and lefty-2. AB - Both lefty-1 and lefty-2 genes are expressed on the left side of developing mouse embryos and are implicated in left-right (L-R) axis formation. With the use of transgenic analysis, the transcriptional regulatory regions of these genes responsible for their L-R asymmetric expression have now been investigated. The 9.5-kb upstream region of lefty-1 and the 5.5-kb upstream region of lefty-2 reproduced the expression pattern of the corresponding gene. Examination of deletion constructs revealed the presence of a left side-specific enhancer (ASE) that is essential and sufficient for lefty-2 asymmetric expression. In contrast, the asymmetric expression of lefty-1 was shown to be determined by a combination of bilateral enhancers and a right side-specific silencer (RSS). The 9. 5-kb region of lefty-1 and the 5.5-kb region of lefty-2 responded to iv and inv, upstream genes of lefty-1 and lefty-2. The regulation of lefty-2 by iv and inv was mediated by ASE. These results suggest that, in spite of the similarities between lefty-1 and lefty-2, different regulatory mechanisms underlie their asymmetric expression. PMID- 9990852 TI - The SCFbeta-TRCP-ubiquitin ligase complex associates specifically with phosphorylated destruction motifs in IkappaBalpha and beta-catenin and stimulates IkappaBalpha ubiquitination in vitro. AB - Ubiquitin-mediated proteolysis has a central role in controlling the intracellular levels of several important regulatory molecules such as cyclins, CKIs, p53, and IkappaBalpha. Many diverse proinflammatory signals lead to the specific phosphorylation and subsequent ubiquitin-mediated destruction of the NF kappaB inhibitor protein IkappaBalpha. Substrate specificity in ubiquitination reactions is, in large part, mediated by the specific association of the E3 ubiquitin ligases with their substrates. One class of E3 ligases is defined by the recently described SCF complexes, the archetype of which was first described in budding yeast and contains Skp1, Cdc53, and the F-box protein Cdc4. These complexes recognize their substrates through modular F-box proteins in a phosphorylation-dependent manner. Here we describe a biochemical dissection of a novel mammalian SCF complex, SCFbeta-TRCP, that specifically recognizes a 19 amino-acid destruction motif in IkappaBalpha (residues 21-41) in a phosphorylation-dependent manner. This SCF complex also recognizes a conserved destruction motif in beta-catenin, a protein with levels also regulated by phosphorylation-dependent ubiquitination. Endogenous IkappaBalpha-ubiquitin ligase activity cofractionates with SCFbeta-TRCP. Furthermore, recombinant SCFbeta-TRCP assembled in mammalian cells contains phospho-IkappaBalpha-specific ubiquitin ligase activity. Our results suggest that an SCFbeta-TRCP complex functions in multiple transcriptional programs by activating the NF-kappaB pathway and inhibiting the beta-catenin pathway. PMID- 9990853 TI - Signal-induced ubiquitination of IkappaBalpha by the F-box protein Slimb/beta TrCP. AB - Signal-induced phosphorylation of IkappaBalpha targets this inhibitor of NF kappaB for ubiquitination and subsequent degradation, thus allowing NF-kappaB to enter the nucleus to turn on its target genes. We report here the identification of an IkappaB-ubiquitin (Ub) ligase complex containing the F-box/WD40-repeat protein, beta-TrCP, a vertebrate homolog of Drosophila Slimb. beta-TrCP binds to IkappaBalpha only when the latter is specifically phosphorylated by an IkappaB kinase complex. Moreover, immunopurified beta-TrCP ubiquitinates phosphorylated IkappaBalpha at specific lysines in the presence of Ub-activating (E1) and conjugating (Ubch5) enzymes. A beta-TrCP mutant lacking the F-box inhibits the signal-induced degradation of IkappaBalpha and subsequent activation of NF-kappaB dependent transcription. Furthermore, Drosophila embryos deficient in slimb fail to activate twist and snail, two genes known to be regulated by the NF-kappaB homolog, Dorsal. These biochemical and genetic data strongly suggest that Slimb/beta-TrCP is the specificity determinant for the signal-induced ubiquitination of IkappaBalpha. PMID- 9990854 TI - Roles of ephrinB ligands and EphB receptors in cardiovascular development: demarcation of arterial/venous domains, vascular morphogenesis, and sprouting angiogenesis. AB - Eph receptor tyrosine kinases and their cell-surface-bound ligands, the ephrins, regulate axon guidance and bundling in the developing brain, control cell migration and adhesion, and help patterning the embryo. Here we report that two ephrinB ligands and three EphB receptors are expressed in and regulate the formation of the vascular network. Mice lacking ephrinB2 and a proportion of double mutants deficient in EphB2 and EphB3 receptor signaling die in utero before embryonic day 11.5 (E11.5) because of defects in the remodeling of the embryonic vascular system. Our phenotypic analysis suggests complex interactions and multiple functions of Eph receptors and ephrins in the embryonic vasculature. Interaction between ephrinB2 on arteries and its EphB receptors on veins suggests a role in defining boundaries between arterial and venous domains. Expression of ephrinB1 by arterial and venous endothelial cells and EphB3 by veins and some arteries indicates that endothelial cell-to-cell interactions between ephrins and Eph receptors are not restricted to the border between arteries and veins. Furthermore, expression of ephrinB2 and EphB2 in mesenchyme adjacent to vessels and vascular defects in ephB2/ephB3 double mutants indicate a requirement for ephrin-Eph signaling between endothelial cells and surrounding mesenchymal cells. Finally, ephrinB ligands induce capillary sprouting in vitro with a similar efficiency as angiopoietin-1 (Ang1) and vascular endothelial growth factor (VEGF), demonstrating a stimulatory role of ephrins in the remodeling of the developing vascular system. PMID- 9990855 TI - Ctf7p is essential for sister chromatid cohesion and links mitotic chromosome structure to the DNA replication machinery. AB - CTF7 (chromosome transmission fidelity) gene in budding yeast encodes an essential protein that is required for high-fidelity chromosome transmission and contains regions of identity conserved from yeast to man. ctf7 mutant cells arrested prior to anaphase onset contain separated sister chromatids. Thus, Ctf7p is essential for cohesion. Cohesion is established during S phase and then maintained until mitosis. However, Ctf7p activity is required only during S phase, suggesting that Ctf7p functions in the establishment of cohesion. In addition, ctf7 genetically interacts with DNA metabolism mutations pol30 (PCNA) and ctf18 (an RF-C like protein) and ctf7 temperature sensitivity and chromosome loss are rescued by high levels of POL30. These findings provide the first evidence that links the establishment of sister chromatid cohesion to the DNA replication machinery and suggest that the assembly of cohesion (and possibly condensation) complexes are coupled to PCNA-dependent DNA replication. The analysis of Ctf7p also reveals an important connection between sister chromatid cohesion, spindle integrity and the spindle assembly checkpoint. PMID- 9990856 TI - Yeast cohesin complex requires a conserved protein, Eco1p(Ctf7), to establish cohesion between sister chromatids during DNA replication. AB - Sister chromatid cohesion is crucial for chromosome segregation during mitosis. Loss of cohesion very possibly triggers sister separation at the metaphase --> anaphase transition. This process depends on the destruction of anaphase inhibitory proteins like Pds1p (Cut2p), which is thought to liberate a sister separating protein Esp1p (Cut1p). By looking for mutants that separate sister centromeres in the presence of Pds1p, this and a previous study have identified six proteins essential for establishing or maintaining sister chromatid cohesion. Four of these proteins, Scc1p, Scc3p, Smc1p, and Smc3p, are subunits of a 'Cohesin' complex that binds chromosomes from late G1 until the onset of anaphase. The fifth protein, Scc2p, is not a stoichiometric Cohesin subunit but it is required for Cohesin's association with chromosomes. The sixth protein, Eco1p(Ctf7p), is not a Cohesin subunit. It is necessary for the establishment of cohesion during DNA replication but not for its maintenance during G2 and M phases. PMID- 9990857 TI - The PERIANTHIA gene encodes a bZIP protein involved in the determination of floral organ number in Arabidopsis thaliana. AB - Mutations in the PERIANTHIA (PAN) gene of Arabidopsis thaliana specifically transform flowers from tetramerous to largely pentamerous, which is a characteristic of flowers of ancestral plants. We have cloned the PAN gene and here we show that it encodes a member of the basic region/leucine zipper class of transcription factors. Immunohistochemical analysis shows that the encoded protein is present in the apical meristem, the floral meristem, each whorl of organ primordia, and in ovule primordia during wild-type flower development. PAN expression occurs independently of genes affecting floral meristem identity, floral meristem size, or floral organ number. The near absence of a phenotype in transgenic plants overexpressing PAN and the contrast between the broad expression of PAN and the specificity of its mutant phenotype suggest that its activity may be regulated post-translationally or by the presence of partner proteins. Based on these results and on data reported previously, we propose models for the role of PAN in the evolution of flower pattern in the mustard family. PMID- 9990858 TI - Double-strand end repair via the RecBC pathway in Escherichia coli primes DNA replication. AB - To study the relationship between homologous recombination and DNA replication in Escherichia coli, we monitored the behavior of phage lambda chromosomes, repressed or not for lambda gene activities. Recombination in our system is stimulated both by DNA replication and by experimentally introduced double-strand ends, supporting the idea that DNA replication generates occasional double-strand ends. We report that the RecBC recombinational pathway of E. coli uses double strand ends to prime DNA synthesis, implying a circular relationship between DNA replication and recombination and suggesting that the primary role of recombination is in the repair of disintegrated replication forks arising during vegetative reproduction. PMID- 9990859 TI - Amino-terminal sequences of sigmaN (sigma54) inhibit RNA polymerase isomerization. AB - In bacteria, association of the specialized sigmaN protein with the core RNA polymerase subunits forms a holoenzyme able to bind promoter DNA, but unable to melt DNA and initiate transcription unless acted on by an activator protein. The conserved amino-terminal 50 amino acids of sigmaN (Region I) are required for the response to activators. We have used pre-melted DNA templates, in which the template strand is unpaired and accessible for transcription initiation, to mimic a naturally melted promoter and explore the function of Region I. Our results indicate that one activity of Region I sequences is to inhibit productive interaction of holoenzyme with pre-melted DNA. On pre-melted DNA targets, either activation of sigmaN-holoenzyme or removal of Region I allowed efficient formation of complexes in which melted DNA was sequestered by RNA polymerase. Like natural pre-initiation complexes formed on conventional DNA templates through the action of activator, such complexes were heparin-resistant and transcriptionally active. The inhibitory sigmaN Region I domain functioned in trans to confer heparin sensitivity to complexes between Region I-deleted holoenzyme and pre-melted promoter DNA. Evidence that Region I senses the conformation of the promoter was obtained from protein footprint experiments. We suggest that one function for Region I is to mask a single-strand DNA-binding activity of the holoenzyme. On the basis of extended DNA footprints of Region I deleted holoenzyme, we also propose that Region I prevents RNA polymerase isomerization, a conformational change necessary for access to and the subsequent stable association of holoenzyme with melted DNA. PMID- 9990860 TI - The role of alphav integrins during angiogenesis. PMID- 9990861 TI - Janus kinases and focal adhesion kinases play in the 4.1 band: a superfamily of band 4.1 domains important for cell structure and signal transduction. AB - The band 4.1 domain was first identified in the red blood cell protein band 4.1, and subsequently in ezrin, radixin, and moesin (ERM proteins) and other proteins, including tumor suppressor merlin/schwannomin, talin, unconventional myosins VIIa and X, and protein tyrosine phosphatases. Recently, the presence of a structurally related domain has been demonstrated in the N-terminal region of two groups of tyrosine kinases: the focal adhesion kinases (FAK) and the Janus kinases (JAK). Additional proteins containing the 4.1/JEF (JAK, ERM, FAK) domain include plant kinesin-like calmodulin-binding proteins (KCBP) and a number of uncharacterized open reading frames identified by systematic DNA sequencing. Phylogenetic analysis of amino acid sequences suggests that band 4.1/JEF domains can be grouped in several families that have probably diverged early during evolution. Hydrophobic cluster analysis indicates that the band 4.1/JEF domains might consist of a duplicated module of approximately 140 residues and a central hinge region. A conserved property of the domain is its capacity to bind to the membrane-proximal region of the C-terminal cytoplasmic tail of proteins with a single transmembrane segment. Many proteins with band 4.1/JEF domains undergo regulated intra- or intermolecular homotypic interactions. Additional properties common to band 4.1/JEF domains of several proteins are binding of phosphoinositides and regulation by GTPases of the Rho family. Many proteins with band 4. 1/JEF domains are associated with the actin-based cytoskeleton and are enriched at points of contact with other cells or the extracellular matrix, from which they can exert control over cell growth. Thus, proteins with band 4.1/JEF domain are at the crossroads between cytoskeletal organization and signal transduction in multicellular organisms. Their importance is underlined by the variety of diseases that can result from their mutations. PMID- 9990863 TI - Sequence polymorphism in two novel Plasmodium vivax ookinete surface proteins, Pvs25 and Pvs28, that are malaria transmission-blocking vaccine candidates. AB - BACKGROUND: For many malarious regions outside of Africa, development of effective transmission-blocking vaccines will require coverage against both Plasmodium falciparum and P. vivax. Work on P. vivax transmission-blocking vaccines has been hampered by the inability to clone the vaccine candidate genes from this parasite. MATERIALS AND METHODS: To search for genes encoding the ookinete surface proteins from P. vivax, the DNA sequences of the eight known proteins in the P25 subfamily (Pfs25, Pgs25, Pys25, Pbs25) and in the P21/28 subfamily (Pfs28, Pgs28, Pys21, Pbs21) of zygote/ookinete surface proteins were aligned. Regions of highest identity were used to design degenerate PCR oligonucleotides. Genomic DNA from the Sal I strain of P. vivax and genomic and splinkerette DNA libraries were used as PCR templates. To characterize the polymorphisms of Pvs25 and Pvs28, these two genes were PCR amplified and the DNA sequences were determined from genomic DNA extracted from patients infected with P. vivax. RESULTS: Analysis of the deduced amino acid sequence of Pvs28 revealed a secretory signal sequence, four epidermal growth factor (EGF)-like domains, six copies of the heptad amino acid repeat (GSGGE/D), and a short hydrophobic region. Because the fourth EGF-like domain has four rather than six cysteines, the gene designated Pvs28 is the presumed homologue of P21/28 subfamily members. Analysis of the deduced amino acid sequence of Pvs25 revealed a similar structure to that of Pvs28. The presence of six rather than four cysteines in the fourth EGF-like domain suggested that Pvs25 is the homologue of P25 subfamily members. Several regions of genetic polymorphisms in Pvs25 and Pvs28 were identified in field isolates of P. vivax. CONCLUSIONS: The genes encoding two ookinete surface proteins, Pvs28 and Pvs25, from P. vivax have been isolated and sequenced. Comparison of the primary structures of Pvs25, Pvs28, Pfs25, and Pfs28 suggest that there are regions of genetic polymorphism in the P25 and P21/28 subfamilies. PMID- 9990864 TI - A 15-year follow-up of AJCC stage III malignant melanoma patients treated postsurgically with Newcastle disease virus (NDV) oncolysate and determination of alterations in the CD8 T cell repertoire. AB - BACKGROUND: The development of effective adjuvant therapies for the treatment of high-risk melanoma patients is critical for the prevention of metastatic disease and improvement of patient survival. Active specific immunotherapy has been tested as an adjuvant treatment in numerous clinical trials with overall limited, but occasionally promising, success rates. Newcastle disease virus (NDV) oncolysate has been utilized as an adjunctive immunotherapeutic agent in the postsurgical management of these patients. A phase II study initiated in 1975 using adjuvant vaccine therapy composed of allogeneic and autologous human melanoma cells infected with live NDV (NDV oncolysate) in patients with AJCC stage III melanoma following therapeutic lymph node dissection has shown >60% survival rate at 10 years with no adverse effects. Continued long-term analysis of trials with promising early results as well as assessment of immunologic responses generated in these patients may result in improved therapeutic decisions for clinical trials in the future. MATERIALS AND METHODS: We analyzed the 15-year survival of patients treated postsurgically with NDV oncolysate in the phase II study described above. In an attempt to understand the immunological effects of this treatment, we have also carried out a comprehensive analysis of the peripheral blood T cell repertoire in these patients. RESULTS: The overall 15 year survival of this group of patients is 55%. Previous studies have suggested that improved outcome in patients undergoing immunotherapy is correlated with increased numbers of CD8(+)CD57(+) cells. In surviving patients, we observed a striking oligoclonality in the CD8(+) T cell population in peripheral blood, which reflects clonal expansions in the CD8(+)CD57(+) subset. CONCLUSIONS: The data suggest that adjuvant vaccination with NDV oncolysates is associated with prolonged survival of patients with lymph node-positive malignant melanoma and that CD8(+) T cells may be an important component of therapeutic efficacy. PMID- 9990865 TI - C1 inhibitor gene sequence facilitates frameshift mutations. AB - Mutations disrupting the function or production of C1 inhibitor cause the disease hereditary angioneurotic edema. Patient mutations identified an imperfect inverted repeat sequence that was postulated to play a mechanistic role in the mutations. To test this hypothesis, the inverted repeat was cloned into the chloramphenicol acetyltransferase gene in pBR325 and its mutation rate was studied in four bacterial strains. These strains were selected to assay the effects of recombination and superhelical tension on mutation frequency. Mutations that revert bacteria to chloramphenicol resistance (Cmr) were scored. Both pairs of isogenic strains had reversion frequencies of approximately 10(-8). These rare reversion events in bacteria were most often a frameshift that involved the imperfect inverted repeat with a deletion or a tandem duplication, an event very similar to the human mutations. Increased DNA superhelical tension, which would be expected to enhance cruciform extrusion, did not accentuate mutagenesis. This finding suggests that the imperfect inverted repeat may form a stem-loop structure in the single-stranded DNA created by the duplex DNA melting prior to replication. Models explaining the slippage can be drawn using the lagging strand of the replication fork. In this model, the formation of a stem loop structure is responsible for bringing the end of the deletion or duplication into close proximity. PMID- 9990868 TI - Analytical Microscopy in the Real Semiconductor Processing World. AB - : In the microelectronic semiconductor world we are bombarded with reports of how the drive toward faster, denser, lower power-consuming and more reliable semiconductor products will accelerate with time. This paper discusses the instrumental evolution from visible light microscopy to scanning electron microscopy and on to transmission electron microscopy and scanned probe microscopy. The increased demands placed on specimen preparation of precise locations in a semiconductor chip for microscopy are discussed. Analytical microscopy has to be timely in order to be a viable adjunct to semiconductor manufacturing. The factors governing analysis of turn-around time are explained and an optimum strategy is suggested for effective utilization of finite laboratory resources. The new instrumentation available to the microscopist is introduced along with an overview of the exciting new analyses that will be available in the immediate future. PMID- 9990869 TI - Study of the Dependence of E2 Energies on Sample Chemistry. AB - : Specimens that charge under electron beam irradiation in the scanning electron microscope (SEM) can be stabilized by choosing the beam energy to be such a value that the sum of the secondary and backscatter electron yields is unity, as this establishes a dynamic charge balance. We show here that for pure elements, the energies E1 and E2, for which charge balance occurs, are related directly to the atomic number of the material. Although generally there is no comparable relation for compounds, we also show that for polymers, the E2 energy is related both to the ratio of the number of valence electrons to molecular weight and to the electronegativity of the monomer units that form the polymer. PMID- 9990870 TI - Correlative Instrumental Neutron Activation Analysis, Light Microscopy, Transmission Electron Microscopy, and X-ray Microanalysis for Qualitative and Quantitative Detection of Colloidal Gold Spheres in Biological Specimens. AB - : Colloidal gold, conjugated to ligands or antibodies, is routinely used as a label for the detection of cell structures by light (LM) and electron microscopy (EM). To date, several methods to count the number of colloidal gold labels have been employed with limited success. Instrumental neutron activation analysis (INAA), a physical method for the analysis of the elemental composition of materials, can be used to provide a quantitative index of gold accumulation in bulk specimens. Given that gold is not naturally found in biological specimens in any substantial amount and that colloidal gold and ligand conjugates can be prepared to yield uniform bead sizes, the amount of label can be calculated in bulk biological samples by INAA. Here we describe the use of INAA, LM, transmission EM, and X-ray microanalysis (EDX) in a model to determine both distribution (localization) and amount of colloidal gold at the organ, tissue, cellular, and ultrastructural levels in whole animal systems following administration. In addition, the sensitivity for gold in biological specimens by INAA is compared with that of inductively coupled plasma-mass spectrometry (ICP MS). The correlative use of INAA, LM, TEM, and EDX can be useful, for example, in the quantitative and qualitative tracking of various labeled molecular species following administration in vivo. PMID- 9990871 TI - Microwave Protocols for Paraffin Microtechnique and In Situ Localization in Plants. AB - : We have developed a microwave protocol for a paraffin-embedding microtechnique of the shoot apical meristem of Zea mays and have successfully applied this protocol to other plant tissues. This protocol decreases the time required for all aspects of microtechnique tissue processing, including fixation (24 hr to 15 min), dehydration (73 hr to 10 min), and infiltration (96 hr to 3 hr). Additionally, the time required to adhere paraffin ribbons to gelatin-coated slides and for the Johanson's safranin O, fast green FCF staining protocol has been significantly decreased. Using this technique, the quality of tissue preservation and subsequent in situ localization of knotted mRNA was increased by using microwaves. PMID- 9990866 TI - Alterations of p16-pRb pathway and chromosome locus 9p21-22 in sporadic invasive breast carcinomas. AB - The p16-pRb pathway represents a vital cell-cycle checkpoint. In the present study we investigated the alterations of this G1-phase protein pathway using immunohistochemical and molecular methods in a series of 55 breast carcinomas and correlated the findings with clinicopathological features of the patients. Furthermore, we examined its relationship with the status of the chromosomal region 9p21-22 performing a deletion map analysis because there are indications that, in addition to CDKN2 and MTS2/p15(INK4B) tumor suppressor genes (TSGs), this area harbors other TSG(s). Aberrant expression (Ab) of p16 and pRb was observed in 26 (47%) and 16 (29%) of the carcinomas, respectively. A statistical trend pointing out an inverse relationship between p16 and pRb expression was found (p = 0.079). Analysis of the region that encodes for p16 by deletion mapping, a PCR-based methylation assay and PCR-SSCP, revealed that deletions and transcriptional silencing by methylation might represent the main mechanisms of CDKN2/p16(INK4A) inactivation in breast carcinomas. The results of deletion mapping also suggest that another TSG(s) may reside at the 9p21-22 area particularly at the D9S162 loci and that co-deletion of this putative gene with CDKN2/p16(INK4A) may play a role in breast carcinogenesis. In addition, microsatellite instability (MI), a marker of replication error phenotype (RER+), was observed with a frequency of 16% in the area examined and was inversely related with loss of heterozygosity (LOH). Interestingly, most cases with MI at the region encoding for p16 were aggregated in a subgroup of breast carcinomas with no other obvious genetic and/or epigenetic CDKN2/p16(INK4A) alterations. We speculate that there is an additional mechanism of CDKN2/p16(INK4A) inactivation. The relationship of p16 protein level pRb, status, the p16-pRb combined immunoprofiles, and the microsatellite alterations detected at the 9p21-22 locus with the patients' clinicopathological parameters revealed two significant correlations: one between normal pRb expression and lymph node involvement (p = 0.0263), and the other between microsatellite alterations (LOH and or MI) and tumor size (p = 9.2 x 10(-3)). In view of the heterogenous nature of breast cancer, we suggest that in a significant proportion of breast carcinomas, deregulation of the p16-pRb pathway in association with another, as-yet unidentified, TSG(s) of the 9p21-22 region may play a role in initiating or progressing the oncogenic procedure, while in other subgroups, alternative molecules may play this role. PMID- 9990872 TI - Real-time Observation of Aluminum Chemical Vapor Deposition in an Environmental Scanning Electron Microscope. AB - : A technique has been developed to provide real-time imaging, with several nanometer resolution, of organometallic chemical vapor deposition (CVD) by scanning electron microscopy under conditions approaching those used in the microelectronics industry. The technique involves modifications to an environmental scanning electron microscope (ESEM) to facilitate organometallic precursor gas handling and sample heating. To demonstrate the usefulness of this technique for studying the microstructural evolution of CVD-grown metal films, results of Al/SiO2 CVD experiments are presented. PMID- 9990874 TI - News and Commentary. PMID- 9990873 TI - Nanomanipulation Experiments Exploring Frictional and Mechanical Properties of Carbon Nanotubes. AB - : In many cases in experimental science, the instrument interface becomes a limiting factor in the efficacy of carrying out unusual experiments or prevents the complete understanding of the acquired data. We have developed an advanced interface for scanning probe microscopy (SPM) that allows intuitive rendering of data sets and natural instrument control, all in real time. The interface, called the nanoManipulator, combines a high-performance graphics engine for real-time data rendering with a haptic interface that places the human operator directly into the feedback loop that controls surface manipulations. Using a hand-held stylus, the operator moves the stylus laterally, directing the movement of the SPM tip across the sample. The haptic interface enables the user to "feel" the surface by forcing the stylus to move up and down in response to the surface topography. In this way the user understands the immediate location of the tip on the sample and can quickly and precisely maneuver nanometer-scale objects. We have applied this interface to studies of the mechanical properties of nanotubes and to substrate-nanotube interactions. The mechanical properties of carbon nanotubes have been demonstrated to be extraordinary. They have an elastic modulus rivaling that of the stiffest material known, diamond, while maintaining a remarkable resistance to fracture. We have used atomic-force microscopy (AFM) to manipulate the nanotubes through a series of configuration that reveal buckling behavior and high-strain resilience. Nanotubes also serve as test objects for nanometer-scale contact mechanics. We have found that nanotubes will roll under certain conditions. This has been determined through changes in the images and through the acquisition of lateral force during manipulation. The lateral force data show periodic stick-slip behavior with a periodicity matching the perimeter of the nanotube. PMID- 9990875 TI - Positron-annihilation studies of the electronic structure of NiO. PMID- 9990877 TI - Lateral displacement of Bragg-reflected x-ray beams. PMID- 9990876 TI - Charged-particle interaction with liquids: Ripplon excitations. PMID- 9990878 TI - Mossbauer study of disordered, quenched Pd80Co20. PMID- 9990879 TI - Ewald methods in molecular dynamics for systems of finite extent in one of three dimensions. PMID- 9990880 TI - Electron capture from a metal surface by slow, multicharged aluminum and carbon ions. PMID- 9990881 TI - Sputtering by fast ions based on a sum of impulses. PMID- 9990882 TI - Metastable states in the narrow soliton regime of Rb2ZnCl4:Mn2+ inferred from ESR measurements. PMID- 9990883 TI - Muon motion in titanium hydride. PMID- 9990884 TI - Theory of multiplet structure in 4d core photoabsorption spectra of CeO2. PMID- 9990885 TI - Mn2+ EPR study of the phase transition in an ammonium sulfate single crystal: Existence of two inequivalent sublattices. PMID- 9990886 TI - Mossbauer study of CuFe0.7Cr1.3O4. PMID- 9990887 TI - Excitation-energy dependence of optically induced ESR in a-Si:H. PMID- 9990888 TI - keV particle bombardment of semiconductors: A molecular-dynamics simulation. PMID- 9990889 TI - 151Eu Mossbauer effect in light rare-earth oxides. PMID- 9990890 TI - Dipolar NMR line shape in a crystal with nonequivalent sites. PMID- 9990891 TI - Relation between the Tc degradation and the correlation gap in disordered superconductors. PMID- 9990892 TI - Shubnikov-de Haas oscillations in intercalation compounds of 2H-TaS2. PMID- 9990894 TI - Superconductivity and charge-density waves. PMID- 9990893 TI - Magnetic pairing mechanism for superconductivity in the Heisenberg model. PMID- 9990895 TI - Tunneling in a spin-density-wave superconductor. PMID- 9990896 TI - Tunneling study of Fermi-liquid effects in amorphous gallium. PMID- 9990898 TI - High-frequency damping of collective excitations in fermion systems. I. Plasmon damping and frequency-dependent local-field factor in a two-dimensional electron gas. PMID- 9990897 TI - Uniaxial incommensurate lattice of a quantum monolayer solid. PMID- 9990899 TI - High-frequency damping of collective excitations in fermion systems. II. Damping of zero sound in normal liquid 3He. PMID- 9990900 TI - Motion of a single superconducting vortex. PMID- 9990901 TI - Onset of superconductivity in ultrathin granular metal films. PMID- 9990902 TI - Competition of pairing and Peierls-charge-density-wave correlations in a two dimensional electron-phonon model. PMID- 9990903 TI - Ginzburg-Landau theory of deformable superconductors. PMID- 9990904 TI - Three-body recombination of spin-polarized atomic hydrogen in very strong magnetic fields. PMID- 9990906 TI - Magnetic resonance of heavy-fermion superconductors and high-Tc superconductors. PMID- 9990905 TI - Three-band charge fluctuation model for electron pairing: A many-body calculation. PMID- 9990907 TI - Dynamics of the two-dimensional spin-1/2 Heisenberg antiferromagnet: Exact results versus Schwinger-boson mean-field theory. PMID- 9990908 TI - Role of nonlinearities in off-critical quenches as described by the Cahn-Hilliard model of phase separation. PMID- 9990909 TI - Structure of incommensurate NiTi(Fe). PMID- 9990911 TI - Phase transitions in RbLiSO4: An optical study. PMID- 9990910 TI - Phase diagram for the generalized Villain model. PMID- 9990912 TI - Electronic and magnetic properties of La2NiO4: The importance of La-O planes. PMID- 9990913 TI - Thermal mixing between spin systems in Al2O3 by a resonant rf electric field. PMID- 9990914 TI - Mixing and displacement in binary two-dimensional condensed phases on a foreign substrate: Mean-field approach and Monte Carlo simulation. PMID- 9990915 TI - Remanent magnetization decay at the spin-glass critical point: A new dynamic critical exponent for nonequilibrium autocorrelations. PMID- 9990916 TI - Thermodynamic functions, freezing transition, and phase diagram of dense carbon oxygen mixtures in white dwarfs. PMID- 9990917 TI - Simulated healing of crystal surfaces. PMID- 9990918 TI - Critical point in the solution of the two magnetic impurity problem. PMID- 9990919 TI - Simulations without critical slowing down: Ising and three-state Potts models. PMID- 9990920 TI - Entropy distribution of a two-level system: An asymptotic analysis. PMID- 9990921 TI - Percolation behavior of long permeable objects: A reference interaction-site model study. PMID- 9990922 TI - Ce-valence instability in the antiferromagnetic and ferromagnetic host series CeMn2(Si1-xGex)2. PMID- 9990923 TI - Neutron flux enhancement using spin-dependent interaction potentials. PMID- 9990924 TI - Field theory of spinodal decomposition: Comparison with numerical simulations. PMID- 9990925 TI - Front propagation into an unstable state in the presence of noise. PMID- 9990926 TI - Influence of topological frustration on the magnetic properties of the normal oxyspinel CdFe2O4. PMID- 9990927 TI - Successive magnetic phase transitions in UBr3. PMID- 9990928 TI - Magnetism and local order. II. Self-consistent cluster calculations. PMID- 9990929 TI - Mechanism of quasilinear temperature dependence of the surface magnetization in a semi-infinite ferromagnet. PMID- 9990931 TI - Wetting, dewetting, and reentrant wetting in Landau theory and lattice mean-field theory. PMID- 9990930 TI - Incommensurate structures in highly ordered complex perovskites Pb(Co1/2W1/2)O3 and Pb(Sc1/2Ta1/2)O3. PMID- 9990932 TI - Effective elastic constants of solids under stress: Theory and calculations for helium from 11.0 to 23.6 GPa. PMID- 9990933 TI - Thermodynamics of the single-channel Kondo impurity of spin S( <= (7/2) in a magnetic field. PMID- 9990934 TI - Spin-polarized Fermi liquids: Applications to liquid 3He. PMID- 9990936 TI - Light scattering study of the glass transition in salol. PMID- 9990935 TI - Concentration dependence of the wave vector of the spin-density wave of chromium alloys. PMID- 9990937 TI - Monte Carlo study of randomly diluted ferromagnetic thin films. PMID- 9990938 TI - Theory of the magnetic phase diagram and magnetostriction of FeGe2. PMID- 9990940 TI - Ammonium-ion ordering in a scheelite lattice: NH4ReO4. PMID- 9990939 TI - Model for binary alloys: An Ising model with isotropic competing interactions. PMID- 9990941 TI - Magnetic and structural ordering in SmH2+x through electrical resistivity measurements. PMID- 9990943 TI - Fracton dynamics of percolating elastic networks: Energy spectrum and localized nature. PMID- 9990942 TI - Numerical study of the two-dimensional Hubbard model. PMID- 9990944 TI - Random-field effects on dynamical scaling in the domain growth of a chemisorbed overlayer. PMID- 9990945 TI - Critical behavior of the two-dimensional XY model: An analysis of extended high temperature series. PMID- 9990946 TI - Boson localization and the superfluid-insulator transition. PMID- 9990947 TI - Path-integral simulation of positronium in a hard sphere. PMID- 9990948 TI - Magnetic and structural properties of amorphous CoTi soft ferromagnetic thin films. I. Magnetic properties. PMID- 9990949 TI - Magnetic and structural properties of amorphous CoTi soft ferromagnetic thin films. II. Structural properties. PMID- 9990950 TI - Green's functions for antiferromagnetic polaritons. I. Surface modes and resonances. PMID- 9990951 TI - Green's functions for antiferromagnetic polaritons. II. Scattering from rough surfaces. PMID- 9990953 TI - Percolation in two-dimensional lattices. I. A technique for the estimation of thresholds. PMID- 9990952 TI - Transport properties and magnetic interactions in acceptor-type magnetic graphite intercalation compounds. PMID- 9990954 TI - Percolation in two-dimensional lattices. II. The extent of universality. PMID- 9990955 TI - Long-time behavior of the cluster size distribution in joint coagulation processes. PMID- 9990956 TI - Wetting on spherical and cylindrical substrates: Global phase diagrams. PMID- 9990957 TI - First-order phase transition in order-disorder ferroelectrics. PMID- 9990959 TI - Attenuation coefficient of first sound in liquid 4He. PMID- 9990958 TI - Nonlinear internal-mode influence on the statistical mechanics of a dilute gas of kinks: The double-sine-Gordon model. PMID- 9990961 TI - Mossbauer-effect study of the Fe hyperfine-field distributions in the ferromagnetic quasicrystal Al40Mn25Fe3Cu7Ge25. PMID- 9990960 TI - Ion-beam mixing at the Fe/SiO2 interface: A conversion-electron Mossbauer spectroscopy and x-ray-diffraction study. PMID- 9990962 TI - In-plane impurities in superconducting layered systems. PMID- 9990964 TI - Origin of the longitudinal-ultrasonic-attenuation peak in heavy-fermion superconductors. PMID- 9990963 TI - Variational calculations of drops of spin-polarized liquid 3He. PMID- 9990966 TI - Excitations in a nearly half-filled Hubbard model with U= PMID- 9990965 TI - Local superconducting coupling in the strong-localization limit of ultrathin granular metal films. PMID- 9990967 TI - 57Fe Mossbauer study of the Tl2Ca1.5Ba1.7(Cu1-xFex)3O9 superconductor. PMID- 9990969 TI - Microscopic equivalence between the two-band model and McMillan proximity-effect theory. PMID- 9990968 TI - Hall effect of Bi-Sr-Ca-Cu-O and Tl-Ba-Ca-Cu-O systems. PMID- 9990970 TI - Memory effect of waves in disordered systems: A real-space approach. PMID- 9990971 TI - Low-temperature properties of quantum Heisenberg helimagnets. PMID- 9990972 TI - HoFe4Al8: An unusual spin glass. PMID- 9990973 TI - Universality class of central-force percolation. PMID- 9990975 TI - Excitation spectrum of a spin-(1/2 chain with competing interactions. PMID- 9990974 TI - Devil's-staircase model of a heterogeneous dielectric. PMID- 9990976 TI - Ising models with competing axial interactions in transverse fields. PMID- 9990977 TI - New Magnetic phases of holmium in a magnetic field. PMID- 9990978 TI - Dynamics of electromagnetic fields in nonlinear Klein-Gordon systems. PMID- 9990979 TI - Baym-Kadanoff criteria and the Ward-Takahashi relations in many-body theory. PMID- 9990980 TI - Effective exponents for critical wetting: The approach to the asymptotic region. PMID- 9990981 TI - Green's-function theory of the spin-1 exchange-interaction model of ferromagnetism. PMID- 9990982 TI - Wetting and displacement of three-dimensional and two-dimensional layers on a foreign substrate. PMID- 9990983 TI - Constructive interference with rotated spin-(1/2 particles: Localization effects on spin relaxation and diffusion. PMID- 9990984 TI - Comment on "Direct observation of relaxation modes in KNbO3 and BaTiO3 using inelastic light scattering" PMID- 9990985 TI - Reply to "Comment on 'Direct observation of relaxation modes in KNbO3 and BaTiO3 using inelastic light scattering' " PMID- 9990986 TI - Erratum:"Functional integral theories of low-dimensional quantum Heisenberg models PMID- 9990987 TI - Grazing-angle neutron diffraction. PMID- 9990989 TI - 39K NMR evidence for a phason gap in K2SeO4. PMID- 9990988 TI - Migration stage of the vacancylike defects in icosahedral Al74Mn20Si6 by positron annihilation techniques. PMID- 9990990 TI - Incomplete wetting of helium I on copper. PMID- 9990991 TI - Muon-spin relaxation studies of weak magnetic correlations in U1-xThxBe13. PMID- 9990992 TI - Melting temperature of two-dimensional electron crystals trapped on thin-film liquid He. PMID- 9990993 TI - Dimensionality expansion for the dirty-boson problem. PMID- 9990995 TI - Pairing of holes in oxide superconductors. PMID- 9990994 TI - Thallium magnetic resonance in superconducting Tl2Ba2Ca2Cu3O10+ delta. PMID- 9990996 TI - Electronic properties of Sr14Cu24O41. PMID- 9990997 TI - Limiting-path model of the critical current in a textured YBa2Cu3O7- delta film. PMID- 9990998 TI - Binding of holes in the Hubbard model with next-nearest-neighbor hopping. PMID- 9991000 TI - Low-temperature thermal conductivity of single-crystal Bi2Sr2CaCu2O8. PMID- 9990999 TI - X-ray absorption of YBa2Cu3O7: A band picture. PMID- 9991002 TI - Ground-state and low-lying excitations of the Heisenberg antiferromagnet. PMID- 9991001 TI - Temperature dependence of hole mobility in Mott insulators: Normal-state resistivity of high-Tc superconductors. PMID- 9991003 TI - Resonating-valence-bond state with fermionic charges and bosonic spins: Mean field theory. PMID- 9991004 TI - Percolation, finite-size scaling, and the thermal scaling power for the Potts model. PMID- 9991005 TI - Multifractal characteristics of magnetic-microsphere aggregates in thin films. PMID- 9991007 TI - Phase transitions in a chemisorbed overlayer studied by infrared spectroscopy: CO on Pt(111). PMID- 9991006 TI - Critical static measurements of the magnetization in the Cd0.6Mn0.4Te spin glass. PMID- 9991008 TI - Dynamics of Cu-Mn spin-glass films. PMID- 9991009 TI - Energy dissipation in a strong magnetic field: Exact model calculation. PMID- 9991010 TI - Scaling laws in fracture. PMID- 9991011 TI - Percolation on ballistic aggregates. PMID- 9991012 TI - Cluster-cluster aggregation of magnetic particles. PMID- 9991013 TI - Spectroscopy of reversible-bleaching centers in hydrogenated SrF2:Pr3+ and CaF2:Pr3+ crystals. PMID- 9991015 TI - EPR study of Fe3+ in alpha -quartz: Characterization of a new type of cation compensated center. PMID- 9991014 TI - Analytic quantum theory of planar positron channeling. PMID- 9991016 TI - Third-order correlation theory of electronic Raman scattering for rare-earth ions in crystals. II. Numerical analysis for ions across the lanthanide series. PMID- 9991017 TI - Effect of x-ray birefringence on radial distribution functions for amorphous materials. PMID- 9991018 TI - Cross-relaxation dynamics of optically excited N-V centers in diamond. PMID- 9991019 TI - EPR study of electron traps in x-ray-irradiated yttria-stabilized zirconia. PMID- 9991020 TI - Dynamic interchange between PMID- 9991022 TI - Short-range order in beta 1-MnZn alloys as investigated by the NMR of 55Mn nuclei. PMID- 9991021 TI - Morphology of Langmuir-Blodgett multilayers: A near-total external fluorescence and reflectivity study. PMID- 9991023 TI - Gap relaxation and its effect on sound attenuation near Tc. PMID- 9991025 TI - Monte Carlo studies of oxygen ordering in the YBa2Cu3-xAxO7- delta systems (A=Ga,Al). PMID- 9991024 TI - Superconducting properties of a single-crystal sphere of ErRh4B4. PMID- 9991026 TI - Possible antipolar pairing mechanism in high-temperature superconductors. PMID- 9991027 TI - Dynamical properties of superconducting arrays. PMID- 9991028 TI - Frost-heave phenomena of 4He on porous glasses. PMID- 9991030 TI - Density of states in the vortex state of type-II superconductors. PMID- 9991029 TI - Heat capacities of LaDx and LaHx (1.9 <= x <= 3.0) from 1 to 300 K. PMID- 9991031 TI - Stability of resonating-valence-bond state in the Hubbard model near half filling. PMID- 9991032 TI - Tensile strength of liquid 4He. PMID- 9991033 TI - Approach to the asymptotic limit in inclusive scattering of neutrons from quantum liquids. PMID- 9991034 TI - Third sound on patterned substrates. I. Periodic and quasiperiodic arrays. PMID- 9991035 TI - Third sound on patterned substrates. II. Random arrays and classical wave localization. PMID- 9991037 TI - Evaluation of the matrix elements with graded-Lie-algebraic operators. PMID- 9991036 TI - Positive curvature of Hc2 in layered superconductors. PMID- 9991038 TI - Dephasing relaxation of J=2 rotons in parahydrogen crystals doped with hydrogen deuterium impurities. PMID- 9991039 TI - Superconductivity and the electronic density of states in disordered two dimensional metals. PMID- 9991040 TI - Velocity-dependent dissipation from free vortices and bound vortex pairs below the Kosterlitz-Thouless transition. PMID- 9991041 TI - Electromagnetic absorption in anisotropic superconductors. PMID- 9991043 TI - Phonons in CaCuO2. PMID- 9991042 TI - Effect of substitutional impurities (Al,Co,Fe,Ga) on the orthorhombic phase of YBa2Cu3O7- delta. PMID- 9991044 TI - Hubbard model with one hole: Ground-state properties. PMID- 9991046 TI - Enhanced pairing interactions in a two-band model. PMID- 9991045 TI - Electronic structure of Pb2Sr2PrCu3O8 as studied by resonant photoemission spectroscopy. PMID- 9991047 TI - Magnetic order and superconductivity in Y1-xPrxBa2Cu3O7. PMID- 9991048 TI - Gap energy and long-range order in the boson-fermion model of superconductivity. PMID- 9991049 TI - Flux lattice melting in high-Tc superconductors. PMID- 9991050 TI - Structural properties of the superconductor LaBa2Cu3-yO7-z in the solid solution system La1+xBa2-xCu3-yO7-z. PMID- 9991051 TI - Raman spectra, superconductivity, and structure of Co-substituted YBa2Cu3O7- delta. PMID- 9991052 TI - Optical properties of copper-oxygen planes in superconducting oxides and related materials. PMID- 9991053 TI - Noise measurement near the transition region in YBa2Cu3O7- delta thin-film superconductor. PMID- 9991054 TI - Origin of the incommensurate modulation of the 80-K superconductor Bi2Sr2CaCu2O8.21 derived from isostructural commensurate Bi10Sr15Fe10O46. PMID- 9991055 TI - Spin-rotation-invariant slave-boson approach to the Hubbard model. PMID- 9991056 TI - Quantitative analysis of x-ray photoemission spectra applied to Bi2Sr2CaCu2O8 high-temperature superconductors. PMID- 9991057 TI - Calculation of the thermal conductivity of single-crystal La2CuO4+ Delta. PMID- 9991058 TI - 17O nuclear-magnetic-resonance spectroscopic study of high-Tc superconductors. PMID- 9991059 TI - Thermopower of zinc-doped Y-Ba-Cu-O. PMID- 9991060 TI - Neel temperature of stoichiometric La2CuO4. PMID- 9991062 TI - Pairing superconductivity in two-dimensional CuO2. PMID- 9991061 TI - Superconducting energy gap and a normal-state excitation in Ba0.6K0.4BiO3. PMID- 9991063 TI - Effects of oxygen and strontium vacancies on the superconductivity of single crystals of Bi2Sr2-xCuO6-y. PMID- 9991064 TI - Ginzburg-Landau-Gorkov theory for high-temperature superconductors. PMID- 9991065 TI - Mid-infrared reflectivity and ellipsometry measurements on single-crystal YBa2Cu3O7 and Bi2Sr2CuO6+y. PMID- 9991066 TI - Simple model for the linewidth of the two-magnon Raman feature observed in high Tc superconductors. PMID- 9991067 TI - Possibility of optical evidence for charge-transfer excitations in YBa2Cu3O7- delta. PMID- 9991068 TI - Energy gaps in Bi-Sr-Ca-Cu-O and Bi-Sr-Cu-O systems by electron tunneling. PMID- 9991069 TI - Photoemission study of monoclinic BaBiO3. PMID- 9991071 TI - Mean-field theory of oxygen-vacancy ordering in YBa2Cu3O7- delta. PMID- 9991070 TI - Exchange-driven pairing of delocalized carriers in high-temperature superconductors. PMID- 9991072 TI - Superconductivity in the liquid-dimer valence-bond state. PMID- 9991073 TI - Glass behavior and the H-T phase diagram of the high-Tc ceramic superconductors YBa2Cu3O7, EuBa2Cu3O7, and GdBa2Cu3O7. PMID- 9991074 TI - Effect of the local charge disproportionation on the electronic structure of BaPb1-xBixO3. PMID- 9991075 TI - Magnetic metal films on paramagnetic substrates: A theoretical study. PMID- 9991076 TI - Wetting transitions near the bulk critical point: Monte Carlo simulations for the Ising model. PMID- 9991077 TI - Griffiths singularities in random magnets: Results for a soluble model. PMID- 9991078 TI - Propagator for the wetting transition in 1+1 dimensions. PMID- 9991079 TI - Criticality at the metastability limit in random-ferromagnet Ising models. PMID- 9991080 TI - Neutron-powder-diffraction study of the structure and antiferromagnetic ordering in Pr2CuO4. PMID- 9991081 TI - Universality and diffusion in nonequilibrium critical phenomena. PMID- 9991082 TI - Linear excitations in the S=(1/2 ferromagnetic chain system (C6D11ND3)CuBr3 studied with neutron scattering. PMID- 9991084 TI - Two-dimensional spin correlations and successive magnetic phase transitions in Nd2CuO4. PMID- 9991083 TI - First-order phase transition in the fcc Heisenberg antiferromagnet. PMID- 9991085 TI - Spinodal decomposition in a two-dimensional fluid model. PMID- 9991086 TI - Theoretical basis for the Vogel-Fulcher-Tammann equation. PMID- 9991087 TI - Brownian motion and finite-temperature effects in the discrete nonlinear Schrodinger equation: Analytic results for the nonadiabatic dimer. PMID- 9991088 TI - Spin-dependent inelastic electron scattering on Ni(110). PMID- 9991089 TI - Domain growth and freezing on a triangular lattice. PMID- 9991090 TI - Charge excitations in the one-dimensional Hubbard model. PMID- 9991091 TI - Pairing mechanism in the CuO2 system based on a variational Monte Carlo study with magnetically frustrated wave function. PMID- 9991092 TI - Molecular-dynamics studies of the mixed cyanides. II. Orientational freezing. PMID- 9991093 TI - Dynamics of continuous-time random walk, fractal time dispersion, and fractional exponential time relaxation. PMID- 9991094 TI - Metastable states of Ising models on the honeycomb lattice. PMID- 9991096 TI - Effective Hamiltonians for Heisenberg antiferromagnets. PMID- 9991095 TI - Diffusion-controlled reactions among spherical traps: Effect of polydispersity in trap size. PMID- 9991097 TI - Monte Carlo calculations of adsorbate structures and the role of the vibrational entropy in phase transitions at surfaces. PMID- 9991099 TI - Statistics of the excitations of the resonating-valence-bond state. PMID- 9991098 TI - Equation-of-state analysis of the effects of an induced staggered field on the phase transition of CoF2. PMID- 9991100 TI - Pseudospin model for KSCN. PMID- 9991101 TI - Spin-1 Heisenberg chain and the one-dimensional fermion gas. PMID- 9991102 TI - Equilibrium magnetic fluctuations of a short-range Ising spin glass. PMID- 9991103 TI - Numerical study of interfacial properties of two-dimensional aperiodic systems. PMID- 9991104 TI - Anisotropy of the resistivity and susceptibility of Kondo systems. PMID- 9991105 TI - Extension of the quantum theory of valence and bonding to molecular and crystal systems with translation symmetry. PMID- 9991106 TI - Critical behavior in spin-reorientation phase transitions: (ErxR1-x)2Fe14B (R=Nd, Dy) magnets. PMID- 9991107 TI - Shape functions of dipolar ferromagnets at and above the Curie point. PMID- 9991109 TI - Surface melting and surface-induced-disorder transitions in thin films: The effect of hidden variables. PMID- 9991110 TI - Phase diagrams for the randomly diluted resistor network and XY model. PMID- 9991108 TI - Coulomb effects in disordered solids. II. A simplified computational method. PMID- 9991112 TI - Microscopic calculation of the spin-stiffness constant for the spin-(1/2 square lattice Heisenberg antiferromagnet. PMID- 9991111 TI - Static properties of an easy-plane ferromagnetic S=1/2 chain: Comparison of numerical results and experimental data on PMID- 9991114 TI - Central-force models which exhibit a splay-rigid phase. PMID- 9991113 TI - Exact solution and thermodynamics of the Hubbard model with infinite-range hopping. PMID- 9991116 TI - Cohn's theorem for elastic networks. PMID- 9991115 TI - Surface energy and free-boson approximation in a competing multispin model. PMID- 9991117 TI - Ion concentrations in a binary liquid mixture: Implications for wetting behavior. PMID- 9991118 TI - Radiation-induced defects in dense phases of crystalline and amorphous SiO2. PMID- 9991119 TI - Energy transfers in the quasielastic scattering of 70-1250-eV electrons by surfaces. PMID- 9991121 TI - Theoretical calculations of the spin-lattice coupling coefficients G11 and G44 for MgO:Ni2+ crystals. PMID- 9991120 TI - Fano antiresonance in the excitation spectra of the luminescence of divalent europium. PMID- 9991122 TI - Possibility of quantum effects reducing the rate of escape from a metastable well. PMID- 9991123 TI - Separation of spin and charge in a Landau quasiparticle wave packet. PMID- 9991124 TI - Application of 1+1-dimensional chiral anomaly to quantization of resistance of a one-dimensional electric subband. PMID- 9991125 TI - Origin of the electronic states near the Fermi level in high-Tc superconductors. PMID- 9991126 TI - Modulated structure in Bi2Sr2Ca1-xYxCu2Oy. PMID- 9991127 TI - Thermoelectric power of Nd1.85Ce0.15CuO4-y and Pr1.85Ce0.15CuO4-y. PMID- 9991129 TI - Dilatometric study of new phase transitions in YBa2Cu3O6.9. PMID- 9991128 TI - Ultrasonic attenuation measurements on thallium-based high-temperature superconductors. PMID- 9991130 TI - Negative moments of currents in percolating resistor networks. PMID- 9991132 TI - Resonant exchange scattering of x rays in ferromagnetic systems. PMID- 9991131 TI - Scaling behavior of systems with coupled order parameters and disorder effects. PMID- 9991133 TI - Neutron-diffraction study of the magnetic structure of UCo2Ge2. PMID- 9991135 TI - Phase diagram of the "2+4" model in a mean-field approximation without correlations. PMID- 9991136 TI - Neutral-fermion-soliton statistics in the short-range resonating-valence-bond state: A reevaluation. PMID- 9991134 TI - Effect of texture and spin reorientation on the magnetic properties of Nd-Fe-B magnets. PMID- 9991138 TI - Comment on "Magnetic interaction between rare-earth moments in high-temperature superconductors RBa2Cu3O7-x" PMID- 9991137 TI - Reply to "Neutral-fermion-soliton statistics in the short-range resonating valence-bond state: A reevaluation" PMID- 9991140 TI - Erratum: "Quantum correction to the equation of state of an electron gas in a semiconductor" PMID- 9991139 TI - Reply to "Comment on 'Magnetic interaction between rare-earth moments in high temperature superconductors RBa2Cu3O7-x.' " PMID- 9991141 TI - Reconciliation of normal-state and superconductive specific-heat, optical, tunneling, and transport data on Y-Ba-Cu-O. PMID- 9991143 TI - Mechanical measurements of two-dimensional flux lattices: Observation of two stage melting. PMID- 9991142 TI - Millimeter-wave surface impedance of YBa2Cu3O7 thin films. PMID- 9991145 TI - Magnetic penetration depth of high-Tc superconductors. PMID- 9991144 TI - Fluctuation effects in heavy-fermion and high-Tc superconductors. PMID- 9991146 TI - Tunneling study on the electron-doped superconductor Nd1.85Ce0.15CuO4-y. PMID- 9991148 TI - Microscopic model for high-Tc oxide superconductors. PMID- 9991147 TI - Anisotropy of the dielectric function in YBa2Cu3O6. PMID- 9991149 TI - Singlet wave functions for the t-J model. PMID- 9991150 TI - Logarithmic-to-nonlogarithmic flux-creep transition and magnetic-flux hardening in Bi-Sr-Ca-Cu-O superconducting ceramics. PMID- 9991152 TI - Vacuum degeneracy of chiral spin states in compactified space. PMID- 9991151 TI - Possible structural phase transition near 210 K of single-phase Bi(Pb)-Sr-Ca-Cu-O superconducting ceramics. PMID- 9991153 TI - Charged magnetic domain lines and the magnetism of high-Tc oxides. PMID- 9991154 TI - Observation of a pressure-induced collapse of the Fe magnetic moment in the strong itinerant ferromagnet Fe72Pt28. PMID- 9991155 TI - Magnetic aftereffect in ultrathin ferromagnetic films. PMID- 9991156 TI - Relationships between cohesive energy, Debye temperature, and the onset of temperature-dependent ion mixing. PMID- 9991157 TI - Holes in the infinite-U Hubbard model: Instability of the Nagaoka state. PMID- 9991158 TI - Elastic scattering in resonant tunneling systems. PMID- 9991159 TI - Multifractal wave functions on a Fibonacci lattice. PMID- 9991160 TI - Density-functional theory of thin films of self-bound fermions. PMID- 9991161 TI - Analysis of Bloch-wall fine structures by magnetic force microscopy. PMID- 9991162 TI - 1/f noise, distribution of lifetimes, and a pile of sand. PMID- 9991163 TI - Cluster and domain-wall dynamics of ferroelectric Sr1-xCaxTiO3. PMID- 9991164 TI - Linear correlation of fractal dimension versus atomic magneton in magnetic particle aggregation. PMID- 9991165 TI - Exact evaluation of the nearest-neighbor Jastrow wave function for the two dimensional spin-(1/2 Heisenberg antiferromagnet. PMID- 9991166 TI - Improved Monte Carlo distribution. PMID- 9991167 TI - Entropic elasticity of a regular fractal. PMID- 9991168 TI - Temperature dependence of sound attenuation in impure metals. PMID- 9991170 TI - Partition function and the density of states for an electron in the plane subjected to a random potential and a magnetic field. PMID- 9991169 TI - 67Zn Mossbauer investigation of Cu-Zn alloys at high pressure. PMID- 9991171 TI - Unoccupied surface states on clean and oxygen-covered Cu(110) and Cu(111). PMID- 9991173 TI - First-principles equation of state of gold. PMID- 9991172 TI - T-matrix approach for the calculation of local fields in the neighborhood of small clusters in the electrodynamic regime. PMID- 9991175 TI - Effect of electron-electron interaction on the thermoelectric power in disordered metallic systems. PMID- 9991174 TI - Diffusion and surface segregation of carbon in alpha -Fe: Molecular-orbital theory. PMID- 9991176 TI - Second-harmonic generation on simple metal surfaces: A quantum-mechanical point of view. PMID- 9991177 TI - Electron-heating effects and the electron-phonon scattering time in thin Sb films. PMID- 9991178 TI - First-principles total-energy calculations on Y and alpha -YH0.5. PMID- 9991180 TI - Analysis of a theoretical model for the incommensurate-to-incommensurate phase transition in NbTe4. PMID- 9991179 TI - Ferromagnetic resonance study of icosahedral and amorphous Al55Mn20Si25 alloys. PMID- 9991181 TI - Charge-density-wave transport under pulsed electric fields in NbSe3: Step structure in sliding distance. PMID- 9991183 TI - Distance of the image plane from metal surfaces. PMID- 9991182 TI - Electronic and structural properties of Cu0.24Ni0.76(110) and thin films of Cu on Ni(110). PMID- 9991184 TI - Light emission from randomly rough tunnel junctions. PMID- 9991185 TI - Temperature dependence of the two-dimensional electronic density of states in disordered metal films. PMID- 9991186 TI - Electron localization and superconducting fluctuations in quasi-two-dimensional Ti films. PMID- 9991187 TI - Anomalous electronic transport behavior, including a Kondo-like effect, for potassium in contact with hydro- and halocarbons. PMID- 9991188 TI - Diffusion and melting in two dimensions: A quasielastic neutron scattering study of alkali metals in graphite. PMID- 9991189 TI - Magnetic hyperfine interaction studies of isolated Ni impurities in Pd and Pd-Pt alloys. PMID- 9991190 TI - Size and structural dependence of the magnetic properties of small 3d-transition metal clusters. PMID- 9991192 TI - DX center in Ga1-xAlxAs alloys. PMID- 9991191 TI - Transient solid-phase crystallization study of chemically vapor-deposited amorphous silicon films by in situ x-ray diffraction. PMID- 9991193 TI - Nonlinear high-frequency conductivity in semiconductors. PMID- 9991194 TI - Ground-state and optical properties of Cu2O and CuO crystals. PMID- 9991195 TI - Electrical conductivity of air-exposed and unexposed lead selenide thin films: Temperature and size effects. PMID- 9991197 TI - Nonparabolicity effects in a quantum well: Sublevel shift, parallel mass, and Landau levels. PMID- 9991196 TI - Surface studies of AIIIB PMID- 9991198 TI - Construction of the crystal potential from the quasi-ion approach. PMID- 9991199 TI - Oxidation kinetics of Si(111) 7 x 7 in the submonolayer regime. PMID- 9991200 TI - Theory of collective excitations in a sawlike quasi-(1+1)-dimensional superlattice. PMID- 9991201 TI - Intrasubband and intersubband plasmons in a semi-infinite Fibonacci HgTe/CdTe superlattice. PMID- 9991202 TI - Degenerate multiwave mixing and phase conjugation in silicon. PMID- 9991204 TI - Solitons, polarons, and excitons in polyacetylene: Step-potential model for electron-phonon coupling in pi -electron systems. PMID- 9991203 TI - Theory of contacts in a two-dimensional electron gas at high magnetic fields. PMID- 9991205 TI - Radiative recombination of two-dimensional electrons in acceptor delta -doped GaAs-AlxGa1-xAs single heterojunctions. PMID- 9991206 TI - Efficient direct calculation method for dielectric response in semiconductors. PMID- 9991207 TI - Piezospectroscopy of GaAs-AlAs superlattices. PMID- 9991208 TI - Surface electronic structure of submonolayer to full-monolayer coverages of alkali metals on GaAs(110): K and Cs. PMID- 9991210 TI - Electronic structures of HgTe and CdTe surfaces and HgTe/CdTe interfaces. PMID- 9991209 TI - Inelastic scattering of electrons from accumulation and inversion layers. PMID- 9991212 TI - Electronic properties of polymeric silicon hydrides. PMID- 9991211 TI - Pressure dependence of the DX center in Ga1-xAlxAs:Te. PMID- 9991213 TI - Interband transitions, plasmons, and dispersion in hexagonal boron nitride. PMID- 9991215 TI - Magnetic field and temperature dependence of the properties of an interface polaron in an arbitrary magnetic field. PMID- 9991214 TI - Surface-phonon polariton on gratings of GaP thin slabs: Raman scattering. PMID- 9991216 TI - Surface acoustic waves on GaAs/AlxGa1-xAs heterostructures. PMID- 9991218 TI - Effects of hydrostatic pressure on the fundamental absorption edge of TlGaSe2. PMID- 9991217 TI - Theory of charge-state splittings of deep levels associated with sulfur pairs in Si. PMID- 9991219 TI - Evidence for threshold effects in positron diffraction from NaF and LiF. PMID- 9991220 TI - Structural transitions in the heavily strained cyanide crystal (KCl)0.25(KCN)0.75. PMID- 9991221 TI - Photoacoustic and ESR studies of iron-doped soda-lime glasses: Thermal diffusivity. PMID- 9991222 TI - Adhesion and bonding of polar and nonpolar SiC and AlN surfaces: Tight-binding band theory. PMID- 9991223 TI - Covalency in oxygen chemisorption as probed by x-ray absorption. PMID- 9991224 TI - Electrons and phonons in polymeric sulfur nitride. PMID- 9991225 TI - Self-consistent band structure of the rutile dioxides NbO2, RuO2, and IrO2. PMID- 9991227 TI - Vibrations of fractals and scattering of light from aerogels. PMID- 9991226 TI - Near-edge x-ray-absorption fine-structure spectroscopy investigation of poly(ethylene oxide)-KI complexes. PMID- 9991229 TI - Photoemission study of formation and oxidation of a cerium-copper interface. PMID- 9991228 TI - Molecular-dynamics investigation of deuteron separation in PdD1.1. PMID- 9991230 TI - Electronic structure of the half-metallic ferromagnet KCrSe2. PMID- 9991231 TI - Calculation of optical transport and localization quantities. PMID- 9991232 TI - Angular distribution of the inverse photoemission from Cu(100). PMID- 9991234 TI - Calculation of core-valence-valence Auger spectra for nonstoichiometric vanadium carbide. PMID- 9991233 TI - First-principles molecular dynamics for metals. PMID- 9991235 TI - Surface phonons localized at step edges. PMID- 9991236 TI - Size-governed electromagnetic absorption by metal particles. PMID- 9991237 TI - Electronic origin of the intermediate phase of NiTi. PMID- 9991238 TI - Quantized helicon absorption and nonlocal effects in a semiconductor superlattice. PMID- 9991239 TI - Electron tunneling in single- and double-barrier structures. PMID- 9991240 TI - Impurity clustering in doped polyacetylene. PMID- 9991241 TI - Self-induced gaps and optical bistability in semiconductor superlattices. PMID- 9991242 TI - Pressure dependence of the optical absorption edge of Cd1-xMnxSe. PMID- 9991243 TI - Isolated As antisite in GaAs: Possibility of the EL2 defect. PMID- 9991244 TI - Calculation of NiSi2-Si Schottky barrier height using an interface-defect model. PMID- 9991245 TI - Dopant-atom-induced disorder in hydrogenated amorphous silicon: Raman studies. PMID- 9991247 TI - Momentum-dependent dielectric function of the cis-transoid conformation of cis polyacetylene. PMID- 9991246 TI - Neutron-diffraction study of the structure of evaporated pure amorphous silicon. PMID- 9991248 TI - Evidence for nonexistence of self-trapped positronium in KI at very low temperatures. PMID- 9991249 TI - Erratum: Effects of thermal diffuse scattering and surface tilt on diffraction and channeling of fast electrons in CdTe PMID- 9991250 TI - Scanning tunneling microscopy of orthorhombic TaS3. PMID- 9991251 TI - Quantum transport in the presence of random traps. PMID- 9991253 TI - Patterson analysis of aperiodic crystals. PMID- 9991252 TI - Tests of the two-state-system model in cold amorphous conductors. PMID- 9991255 TI - Invertibility of the density-density response function at complex frequencies. PMID- 9991254 TI - Structural relaxation induced by passing electric current in amorphous Cu50Ti50 at low temperatures. PMID- 9991256 TI - High-pressure study of a charge-density-wave compound (NbSe4)10/3I. PMID- 9991258 TI - Optical properties of the SbGa heteroantisite defect in GaAs:Sb. PMID- 9991257 TI - Phonon dispersion measurements and first-principles calculations for the Au(110) surface. PMID- 9991259 TI - Electron-spin resonance of the two-dimensional electron gas in Ga0.47In0.53As-InP heterostructures. PMID- 9991260 TI - Incompressible quantum Hall states. PMID- 9991261 TI - Transition from Ohmic to adiabatic transport in quantum point contacts in series. PMID- 9991262 TI - Band-gap renormalization and band-filling effects in a homogeneous electron-hole plasma in In0.53Ga0.47As/InP single quantum wells. PMID- 9991263 TI - Possibility of a metal-insulator transition at the Mott critical field in InSb and Hg1-xCdxTe. PMID- 9991264 TI - Observation of a new mode in the energy-loss spectrum of the Sb/GaAs(110) system. PMID- 9991265 TI - Magnetoabsorption spectra of band-edge excitons in 2H-PbI2 at high magnetic fields up to 40 T. PMID- 9991266 TI - Time-resolved Raman studies of the photoexcited electron-hole plasma in InP. PMID- 9991267 TI - Magnetic depopulation of hybrid magnetoelectric subbands in a quantum-well wire under an axial magnetic field. PMID- 9991268 TI - Dynamics of the spin-glass freezing in semimagnetic semiconductors. PMID- 9991269 TI - Theory of photoemission and inverse-photoemission spectra of highly correlated electron systems: A weak-coupling 1/N expansion. PMID- 9991270 TI - Amorphization reaction in thin films of elemental Cu and Y. PMID- 9991272 TI - Electrical linear-response theory in an arbitrary magnetic field: A new Fermi surface formation. PMID- 9991271 TI - Sticking in the quantum regime: H2 and D2 on Cu(100). PMID- 9991273 TI - Exactly soluble model for antiphase boundaries in binary ordering alloys. PMID- 9991275 TI - High-resolution electron-energy-loss spectroscopy: Relationship between loss intensity and coverage. PMID- 9991274 TI - Electronic structure and magnetic properties of dilute Fe alloys with transition metal impurities. PMID- 9991276 TI - Medium-energy ion-scattering analysis of the c(2 x 2) structure induced by K on Au(110). PMID- 9991277 TI - Scaling analysis of quasiperiodic systems: Generalized Harper model. PMID- 9991278 TI - Absence of effective electron-photon scattering in a tunneling chain of quantum dots. PMID- 9991279 TI - Low-energy electron diffraction study of multilayer relaxation on a Pb{110} surface. PMID- 9991280 TI - Mode conversion and the electron-phonon distribution in nonequilibrium metal films. PMID- 9991281 TI - Laser-induced Nernst-Ettingshausen effect: Anomalous dependency on the magnetic field. PMID- 9991282 TI - Structural studies of Co/Cr multilayered thin films. PMID- 9991283 TI - Localization in the Soukoulis-Economou model of one-dimensional incommensurate systems. PMID- 9991284 TI - Transmission and reflection of transverse-magnetic-polarized optical fields at stratified nonlinear media. PMID- 9991285 TI - Correlations and fluctuations in reflection coefficients for coherent wave propagation in disordered scattering media. PMID- 9991287 TI - Growth-driven ordering and anisotropy in semiconductor alloys. PMID- 9991286 TI - Surface polaron: Statics. PMID- 9991288 TI - Temperature-dependent Al/GaAs(110) interface formation and adatom energy references. PMID- 9991290 TI - Spectroscopic investigation of the electronic states in narrow coupled GaAs/AlAs quantum wells with indirect band structure. PMID- 9991289 TI - Resonant Raman scattering mediated by intrinsic excitons in Cd1-xZnxTe (x~0.5). PMID- 9991291 TI - Low-temperature energy excitations and thermal properties of silica aerogels. PMID- 9991292 TI - Inelastic electron scattering from clean and arsenic-overcoated GaAs(100). PMID- 9991293 TI - Orbital magnetoconductance in the variable-range-hopping regime. PMID- 9991294 TI - Subband structures of GaAs/AlxGa1-xAs multiple quantum wells. PMID- 9991295 TI - Fermi-level pinning and interface states at CaF2/Si(111). PMID- 9991296 TI - Tranverse magnetotunneling in AlxGa1-xAs capacitors. I. Angular dependence. PMID- 9991298 TI - Excitons in double quantum wells. PMID- 9991297 TI - Experimental determination of the valence-band structure of molecular-beam epitaxy-grown CdTe(110). PMID- 9991299 TI - d-function approach to the electromagnetic response of semiconductor heterostructures. PMID- 9991300 TI - Infrared-active vibrational modes of heavily doped "metallic" polyacetylene. PMID- 9991301 TI - Mixing enthalpy of the GaAs-AlAs random alloy: 64-atom supercell calculations. PMID- 9991302 TI - Shallow and deep impurity levels in multivalley semiconductors: A Green-function study of a cubic model by the recursion method. PMID- 9991303 TI - Shallow and deep impurity levels in multivalley semiconductors: A Green-function study of silicon by the recursion method. PMID- 9991304 TI - Theory of optical spectra in a magnetic field in doped semiconductor quantum wells: Impurity-induced broadening and transitions. PMID- 9991305 TI - Resonant inverse-photoemission study of layer-dependent surface states at the epitaxial GaAs(110)-Bi interface. PMID- 9991306 TI - Anomalous photoquenching in semi-insulating GaAs attributed to the presence of the deep donor ELO. PMID- 9991307 TI - Energy distribution of donor ground states in mixed crystals. PMID- 9991308 TI - Comparative study of water adsorption on Ge(100)-(2 x 1) and GexSi1-x(100)-(2 x 1) by high-resolution electron-energy-loss spectroscopy. PMID- 9991309 TI - Electron momentum distribution in cadmium sulfide. PMID- 9991311 TI - Electronic structure and optical properties of strained GaSb/AlSb quantum wells under uniaxial stress. PMID- 9991310 TI - Pressure dependence of phonon modes in GaAs/AlAs superlattices. PMID- 9991312 TI - Calculated shallow-donor-level binding energies in GaAs-AlxGa1-xAs quantum wells. PMID- 9991314 TI - Two-dimensional electron-acoustic-phonon interaction at high magnetic fields: Thermal conductance in GaAs/AlxGa1-xAs heterostructures. PMID- 9991313 TI - Photoreflectance from GaAs and GaAs/GaAs interfaces. PMID- 9991315 TI - Quantum subband interference effect on the exciton spectra in semiconductor quantum wells. PMID- 9991316 TI - Cyclotron resonance in a two-dimensional electron gas in a tilted magnetic field. PMID- 9991317 TI - Electronic structures of zero-dimensional quantum wells. PMID- 9991318 TI - Electronic structures of superlattices under in-plane magnetic field. PMID- 9991319 TI - Intermolecular interactions in pi -conjugated systems: Application to polyenes. PMID- 9991321 TI - Bethe-Bloch stopping-power parameters for Mylar, Kapton, and Havar targets derived from measurements with proton, alpha -particle, and carbon-ion projectiles. PMID- 9991320 TI - Ionizing-radiation effects in lanthanum magnesium aluminate crystals. PMID- 9991322 TI - Ultrasonic spectrum in Fibonacci acoustic superlattices. PMID- 9991323 TI - Exchange interactions of quench-condensed vanadium atoms on metal surfaces. PMID- 9991324 TI - Equilibrium configuration of bond-centered H0 in GaAs. PMID- 9991325 TI - Coherent and sequential tunneling in double barriers with transverse magnetic fields. PMID- 9991326 TI - Acoustic deformation potentials in AIB PMID- 9991327 TI - Color-center-induced band-gap shift in yttria-stabilized zirconia. PMID- 9991328 TI - Comment on "Experimental test of the Mie theory for microlithographically produced silver spheres" PMID- 9991329 TI - Effects of the constriction geometry on quasi-one-dimensional transport: Adiabatic evolution and resonant tunneling. PMID- 9991330 TI - Bonding properties of mercury dimers in the pseudopotential local-density approximation scheme. PMID- 9991331 TI - Vibrational phase relaxation of the metal-molecule stretch mode: CO on Pt(111). PMID- 9991332 TI - Optical properties of InAs/AlAs strained-layer superlattices. PMID- 9991334 TI - Raman scattering from surface and bulk acoustic phonons in capped superlattices. PMID- 9991333 TI - Raman scattering of InAs/AlAs strained-layer superlattices. PMID- 9991335 TI - Interlayer Gamma -X scattering in staggered-alignment Al0.34Ga0.66As-AlAs ternary alloy multiple-quantum-well structures. PMID- 9991336 TI - Size-dependent radiative decay of excitons in CuCl semiconducting quantum spheres embedded in glasses. PMID- 9991337 TI - Short-range order in electron-irradiated Cu-Pd: Fluctuations in a nonequilibrium steady state. PMID- 9991338 TI - Search for adiabatic positronium emission from a metal surface. PMID- 9991339 TI - Positron annihilation in vacancies: Korringa-Kohn-Rostoker formulation and application to Cu. PMID- 9991340 TI - Mossbauer analysis of ultrathin ferromagnetic Fe(110) films on W(110) coated by Ag. PMID- 9991341 TI - Muon tunneling and spin relaxation in iron. PMID- 9991342 TI - Effect of diamagnetic doping on the magnetic resonance in a quasi-one-dimensional system tetramethylammonium manganese trichloride. PMID- 9991343 TI - Effect of velocity variation on secondary-ion-emission probability: Quantum stationary approach. PMID- 9991345 TI - Predicted intensities for new Raman transitions in solid HD. PMID- 9991344 TI - Green's function in proximity-contact superconducting-normal double layers. PMID- 9991346 TI - Subharmonic energy-gap structure and heating effects in superconducting niobium point contacts. PMID- 9991347 TI - Magnetic susceptibility of 3He at large molar volume. PMID- 9991348 TI - Evidence for spin fluctuations in vanadium from a tunneling study of Fermi-liquid effects. PMID- 9991349 TI - Thermally induced flux motion and the elementary pinning force in Nb thin films. PMID- 9991350 TI - Kapitza resistance between a solid wall and superfluid 4He near T lambda. PMID- 9991351 TI - Consequences of time-reversal-symmetry violation in models of high-Tc superconductors. PMID- 9991352 TI - Quantum mechanics of the fractional-statistics gas: Hartree-Fock approximation. PMID- 9991353 TI - Thermal properties of heavy-fermion CeRu2Si2. PMID- 9991354 TI - Electronic structure of clean and Ag-covered single-crystalline Bi2Sr2CuO6. PMID- 9991355 TI - Quantum percolation and lattice instabilities in high-Tc cuprate superconductors. PMID- 9991356 TI - Superconducting UPt3 in a magnetic field. PMID- 9991357 TI - Specific heat of mechanically alloyed amorphous Zr0.7Ni0.3. PMID- 9991358 TI - Flow of superfluid 3He-B past a specular wall: A finite-temperature calculation. PMID- 9991359 TI - Monte Carlo study of transient states of order in YBa2Cu3Oz. PMID- 9991360 TI - Electronic structure of copper-oxygen clusters in the high-Tc superconductor La2 xSrxCuO4. PMID- 9991361 TI - Theoretical study of the structural dependence of nuclear quadrupole frequencies in high-Tc superconductors. PMID- 9991362 TI - Magnetic field dependence of the thermoelectric power of superconducting Bi-Sr-Ca Cu-O. PMID- 9991363 TI - Scaling law and flux pinning in polycrystalline La1.85Sr0.15CuO4. PMID- 9991364 TI - X-ray-absorption study of charge-density ordering in (Ba1-xKx)BiO3. PMID- 9991365 TI - Kosterlitz-Thouless transition in Tl2Ba2CaCu2O8 thin films. PMID- 9991367 TI - Calculations of the electronic structure and superconducting properties of the Ba(K)Pb(Bi)O3 system. PMID- 9991366 TI - Photoemission study of absorption mechanisms in Bi2.0Sr1.8Ca0.8La0.3Cu2.1O8+ delta, BaBiO3, and Nd1.85Ce0.15CuO4. PMID- 9991368 TI - Tracer diffusion of oxygen in YBa2Cu3O7- delta. PMID- 9991369 TI - Thermal expansivity below 300 K and low-temperature heat capacity of YBa2Cu3O7. PMID- 9991370 TI - Properties that change as superconductivity disappears at high-doping concentrations in La2-xSrxCuO4. PMID- 9991371 TI - Cu nuclear quadrupole resonance and far-infrared reflectance of superconducting (Y1-yCay)Ba2Cu3O6. PMID- 9991373 TI - Possible observation of a spin-density wave in La2CuO4 by Raman scattering. PMID- 9991372 TI - Specific heat and magnetic order in GdBa2-xSrxCu3O7. PMID- 9991374 TI - Phenomenological model of the magnetic properties of La2-xSrxCuO4-y. PMID- 9991375 TI - Electronic-geometric relationships in copper-oxide-based superconductors. PMID- 9991376 TI - Oxygen-disorder effects on the electronic structure of YBa2Cu3O6+ delta. PMID- 9991377 TI - Class of variational singlet wave functions for the Hubbard model away from half filling. PMID- 9991379 TI - Valence bonds and the Lieb-Schultz-Mattis theorem. PMID- 9991378 TI - Critical behavior of the two-dimensional anisotropic Heisenberg antiferromagnet: A numerical test of spin-wave theory. PMID- 9991380 TI - High-temperature expansions on Sierpinski carpets. PMID- 9991381 TI - Nucleation and growth in systems with two stable phases. PMID- 9991382 TI - Raman intensities near second-order transitions: RP5O14 ferroelastics (where R is a lanthanide). PMID- 9991383 TI - Superspace symmetry modes and incommensurate-to-incommensurate phase transition in NbTe4. PMID- 9991384 TI - Two-dimensional melting: Electrons on helium. PMID- 9991385 TI - Dynamics of dislocation-mediated melting in a two-dimensional lattice in the presence of an oscillatory applied strain. PMID- 9991386 TI - Anomalous behavior of the weak itinerant ferromagnet Sc3In under hydrostatic pressure. PMID- 9991387 TI - Anomalous proton spin-lattice relaxation at high temperatures in bcc transition metal-hydrogen solid-solution systems. PMID- 9991388 TI - Hole dynamics in the t-J model: An exact diagonalization study. PMID- 9991389 TI - Ground-state energy of the one- and two-dimensional Hubbard model calculated by the method of Singwi, Tosi, Land, and Sjolander. PMID- 9991390 TI - Critical behavior of a frustrated Ising system. PMID- 9991391 TI - Dynamic disorder, renewal, and anomalous diffusion. PMID- 9991392 TI - Metallic ferromagnetism in a single-band model. II. Finite-temperature magnetic properties. PMID- 9991394 TI - Finite-temperature magnetism of disordered Fe-Co alloys. PMID- 9991393 TI - Dynamics of ordering in highly degenerate models with anisotropic grain-boundary potential: Effects of temperature and vortex formation. PMID- 9991395 TI - Influence of deviations from ideal stoichiometry on the anisotropy parameters of magnetite Fe3(1- delta )O4. PMID- 9991396 TI - Phase transition in the antiferromagnetic mixture CsMn1-xCoxCl3 PMID- 9991397 TI - Low-temperature properties of the Hubbard chain with an attractive interaction. PMID- 9991398 TI - Spin-wave spectrum of a superlattice with antiferromagnetic interfacial coupling. PMID- 9991399 TI - Finite-size scaling study of the three-dimensional classical XY model. PMID- 9991400 TI - Influence of spin fluctuations on the specific heat and entropy of weakly itinerant ferromagnets. PMID- 9991401 TI - Electrokinetic effects in fluid-saturated poroelastic media. PMID- 9991402 TI - Spin-correlation functions of the S=1 Heisenberg-Ising chain by the large-cluster decomposition Monte Carlo method. PMID- 9991403 TI - Monte Carlo study of the W(001) surface reconstruction transition based on total energy calculations. PMID- 9991404 TI - Biased-diffusion calculations of electrical transport in inhomogeneous continuum systems. PMID- 9991406 TI - Formation of a glassy solid by computer simulation. PMID- 9991405 TI - Mean-field theory for vacancies in a quantum antiferromagnet. PMID- 9991408 TI - Order and disorder in the resonating-valence-bond state. PMID- 9991407 TI - Resonances in recombination of atomic hydrogen due to long-range H3 molecular states. PMID- 9991410 TI - Nonlinear dynamics of a quantum ferromagnetic chain: Spin-coherent-state approach. PMID- 9991409 TI - Extension of Nagaoka's theorem on the large-U Hubbard model. PMID- 9991411 TI - Classification of interfacial wetting behavior in binary liquid mixtures. PMID- 9991412 TI - Finite-size scaling of O(n) models with long-range interactions. PMID- 9991413 TI - epsilon expansion for the Nishimori multicritical point of spin glasses. PMID- 9991414 TI - Elastic and superelastic percolation networks: Imperfect duality, critical Poisson ratios, and relations between microscopic models. PMID- 9991415 TI - Anomalous Warburg impedance and universal surface magnetic exponent for Gaussian models in the presence of fractal boundaries. PMID- 9991416 TI - Nonlinear effects in the dynamics of an antiferromagnetic chain. PMID- 9991417 TI - Spectrum of the correlation matrix in short-range Ising spin glasses. PMID- 9991418 TI - Relativistic electron-electron interaction in impure superconductors. PMID- 9991420 TI - Critical temperature and superconducting gap in a model of high-Tc superconductivity. PMID- 9991419 TI - Tunneling measurements of Nd1.85Ce0.15CuOx. PMID- 9991421 TI - Magnon and phonon Raman scattering in Bi2Sr2Ca1-xYxCu2O8+y. PMID- 9991422 TI - Extrapolated residual resistivity in high-Tc oxide materials. PMID- 9991423 TI - Magnetic field modulation effects on the microwave transmission through superconducting thin films of Y-Ba-Cu-O. PMID- 9991424 TI - Ground-state energy of some staggered spin-(1/2 antiferromagnetic XXZ Heisenberg chains. PMID- 9991425 TI - Exchange and correlation effects in anisotropic systems. PMID- 9991426 TI - Quantum Boltzmann equation and Kubo formula for electronic transport in solids. PMID- 9991427 TI - Thermopower behavior in La2Mo2O7: A possible charge-density-wave system with partial Fermi-surface nesting. PMID- 9991428 TI - Phason instabilities and successive wave-vector reorientation phase transitions in MnSi. PMID- 9991430 TI - Phase diagram for the infinite-range transverse Ising spin-glass model. PMID- 9991429 TI - Origin of the difference in the magneto-optical Kerr effect between PtMnSb and NiMnSb. PMID- 9991432 TI - Axial next-nearest-neighbor Ising model, dipole-dipole interactions, and the phase transitions of NaNO2. PMID- 9991431 TI - Sound attenuation and dispersion in a diluted Ising model. PMID- 9991433 TI - Diverging resistivity anisotropy with decreasing temperature in 60-K YBa2Cu2O7-y. PMID- 9991435 TI - X-ray resonance exchange scattering in dysprosium. PMID- 9991434 TI - Effects of yttria concentration on the EPR signal in x-ray-irradiated yttria stabilized zirconia. PMID- 9991436 TI - Electron-energy-loss spectroscopy studies of icosahedral-phase plasmons. PMID- 9991437 TI - Polarization memory of multiply scattered light. PMID- 9991438 TI - Spin fluctuations of trivalent Sm ions in gamma -Ce, alpha -Ce, and La. PMID- 9991439 TI - Critical state in disk-shaped superconductors. PMID- 9991440 TI - Transient-thermoreflectance study of single-crystal lanthanum cuprate. PMID- 9991441 TI - Specific heat of pure and thoriated UBe13 at low temperatures in high magnetic fields. PMID- 9991442 TI - Twins and anisotropies of the superconducting order parameter in YBa2Cu3O7. PMID- 9991443 TI - Electron tunneling study of the normal and superconducting states of Bi1.7Pb0.3Sr2CaCu2Ox. PMID- 9991444 TI - Structure and oxygen stoichiometry for the electron-doped cuprate superconductor Nd1.85Ce0.15CuO4- delta. PMID- 9991445 TI - Thermopower in epitaxial YBa2Cu3O7 thin films. PMID- 9991446 TI - Heavy-fermion behavior in CeInPt4. PMID- 9991447 TI - Kinetic energy of electrons on a two-dimensional lattice with commensurate flux. PMID- 9991448 TI - Nature of empty states in YBa2Cu3O7-x. PMID- 9991450 TI - Magnetic field dependence of ultrasound velocity in high-Tc superconductors. PMID- 9991449 TI - Anisotropy of the thermal conductivity of YBa2Cu3O7-y. PMID- 9991451 TI - Stable tenfold faceted single-grain decagonal quasicrystals of Al65Cu15Co20. PMID- 9991453 TI - New superconducting state of the Anderson-lattice model. PMID- 9991452 TI - Magnetic and resistive measurements of the superconducting critical fields of melt-cast Ba0.65K0.35BiO3. PMID- 9991454 TI - Correlations among c/b, Tc, and Madelung potentials in the system of RBa2Cu3Ox superconductors. PMID- 9991455 TI - Specific-heat exponent and critical-amplitude ratio at the Lifshitz multicritical point. PMID- 9991456 TI - Liquid crystals at high dimensionality. PMID- 9991457 TI - Wavelength intensity correlation functions for transmitted waves through a slab: Numerical results. PMID- 9991459 TI - Annealed versus quenched diffusion coefficient in random media. PMID- 9991458 TI - Wick's theorem for charged spin systems. PMID- 9991461 TI - Dynamics of nonequilibrium large-wave-vector magnons in MnF2. PMID- 9991460 TI - Spin-cluster relaxation times in the spin glass PMID- 9991462 TI - Low-temperature adsorption of H2S on Ni(001) studied by near-edge- and surface extended-x-ray-absorption fine structure. PMID- 9991463 TI - Spectra and energy levels of Tm3+:Y3Al5O12. PMID- 9991464 TI - Elastic properties of grain boundaries in copper and their relationship to bulk elastic constants. PMID- 9991465 TI - Electronically stimulated dissociation of NO2 on Pt(111). PMID- 9991466 TI - Energy spectrum and persistent current in one-dimensional rings. PMID- 9991467 TI - Spin density of ordered FeCo: A failure of the local-spin-density approximation. PMID- 9991468 TI - Electronic structure of the actinide-Rh3 systems and the 5f localization in UPd3. PMID- 9991469 TI - Electronic structure and magnetic properties of selected lanthanide and actinide intermetallic Laves-phase alloys. PMID- 9991471 TI - Dielectric breakdown of a random array of conducting cylinders. PMID- 9991470 TI - Scanning tunneling microscopy of NbSe3 and orthorhombic TaS3. PMID- 9991472 TI - Thermal conductivity and electrical resistivity of gadolinium as functions of pressure and temperature. PMID- 9991473 TI - Jump frequency of silver ions for diffusion in alpha -Ag2Te. PMID- 9991474 TI - Electrical properties of transition-metal carbides of group IV. PMID- 9991475 TI - Formation of a hydrogenic state near a metal surface. PMID- 9991476 TI - Molecular-dynamics study of the reconstructed Au(111) surface: Low temperature. PMID- 9991477 TI - Magnetic properties of icosahedral Al-Mo-Fe and Al-Ta-Fe alloys. PMID- 9991478 TI - Raman studies of black phosphorus from 0.25 to 7.7 GPa at 15 K. PMID- 9991479 TI - Image-potential states on dielectric-covered metal surfaces: Variational versus numerical approach. PMID- 9991480 TI - Theory of the photopyroelectric method for investigation of optical and thermal materials properties. PMID- 9991481 TI - Optical properties of the sulfur-related isoelectronic bound excitons in Si. PMID- 9991482 TI - Thermal and structural damping of the multiple-scattering contributions to the x ray-absorption coefficient. PMID- 9991483 TI - Structural investigation of a-Si and a-Si:H using x-ray-absorption spectroscopy at the Si K edge. PMID- 9991484 TI - Valence- and conduction-band densities of states for tetrahedral semiconductors: Theory and experiment. PMID- 9991485 TI - Optical-bias-enhanced transient photocurrent in amorphous silicon. PMID- 9991486 TI - Two helical conformations of polythiophene, polypyrrole, and their derivatives. PMID- 9991488 TI - Effective bond-orbital model for acceptor states in semiconductors and quantum dots. PMID- 9991487 TI - Electron trapping by metastable effective-mass states of DX donors in indirect band-gap AlxGa1-xAs:Te. PMID- 9991489 TI - Temperature dependence of the exciton population in emission spectra of GaAs single quantum wells with enlarged monolayer-flat growth islands. PMID- 9991490 TI - Angle-resolved photoemission study of thin molecular-beam-epitaxy-grown alpha Sn1-xGex films with x~0.5. PMID- 9991492 TI - Empirical potential-based Si-Ge interatomic potential and its application to superlattice stability. PMID- 9991491 TI - High-pressure phase transition in gallium phosphide: An x-ray-absorption spectroscopy study. PMID- 9991493 TI - Quasiparticle properties of a coupled two-dimensional electron-phonon system. PMID- 9991494 TI - Localization and hopping conductivity in the quantum Hall regime. PMID- 9991495 TI - Electron-phonon interactions in modulation-doped AlxGa1-xAs/GaAs heterojunctions. PMID- 9991497 TI - Theoretical and experimental picosecond photoluminescence studies of the quantum confined Stark effect in a strongly coupled double-quantum-well structure. PMID- 9991496 TI - Electroabsorption of polyacetylene. PMID- 9991498 TI - Effect of oxygen adsorption on instability in electrical resistance of CdSe0.6Te0.4 thin films. PMID- 9991499 TI - Photoluminescence studies of planar-doped GaAs-Ga1-xAlxAs multiple-quantum-well structures. PMID- 9991500 TI - Effect of alloy disorder on the vibrational spectrum of silicon donors in AlxGa1 xAs. PMID- 9991502 TI - X-ray interference in ultrathin epitaxial layers: A versatile method for the structural analysis of single quantum wells and heterointerfaces. PMID- 9991501 TI - Transmission and frequency spectra of acoustic phonons in Thue-Morse superlattices. PMID- 9991503 TI - Development of rare-earth-semiconductor interfaces: Ce/InP(110), Sm/InSb(110), and Ce/CdTe(110). PMID- 9991504 TI - Relaxation of zinc-blende (110) surfaces. PMID- 9991505 TI - Surface core-level shifts on InP(110): Experiments and Madelung energy calculations. PMID- 9991506 TI - Magnetotunneling in double-barrier heterostructures. PMID- 9991508 TI - Electronic structure of semiconducting alkali-metal silicides and germanides. PMID- 9991507 TI - Microscopic nature of coordination defects in amorphous silicon. PMID- 9991509 TI - Exciton-phonon system in a polar semiconductor quantum well. PMID- 9991511 TI - Intensity of the RR longitudinal optical phonon branch for Raman scattering by solid HD. PMID- 9991510 TI - Effect of disorder on the Mott constant in n-type semiconductors. PMID- 9991513 TI - Unification of polaron and soliton theories of exciton transport. PMID- 9991512 TI - Unusual dielectric relaxation of the mixed crystal (KBr)1-x(KCN)x at low temperatures and at low defect concentrations. PMID- 9991514 TI - Electron-energy-loss studies of dislocations in diamond. PMID- 9991516 TI - First-principles lattice dynamics of almost-unstable zinc-blende structures. PMID- 9991515 TI - Random magnetic anisotropy in thin films of amorphous Mn48B52. PMID- 9991517 TI - Electronic structure of (diamond C)/(sphalerite BN) (110) interfaces and superlattices. PMID- 9991518 TI - Surface polaron in the vicinity of two orthogonal surfaces. PMID- 9991519 TI - Formation kinetics of (F2+)H centers in NaCl:OH- crystals. PMID- 9991521 TI - Dephasing and quantum localization in disordered systems. PMID- 9991520 TI - Ce3+:Na+ pairs in CaF2 and SrF2: Absorption and laser-excitation spectroscopy, and the observation of hole burning. PMID- 9991522 TI - Yb on Al: Substrate- and adsorbate-induced Yb contraction. PMID- 9991523 TI - Amorphous deposits with energies below the crystal energy. PMID- 9991525 TI - Force-balance theory and dynamic-response theory of quantum nonlinear transport. PMID- 9991524 TI - Multiple-scattering solutions to the Schrodinger equation for semi-infinite layered materials. PMID- 9991526 TI - High-temperature vacancy concentration in Cu. PMID- 9991527 TI - Localization in a quantum Hall regime: Mixed short- and long-range scatterers. PMID- 9991528 TI - Effects of barrier phonons on the tunneling current in a double-barrier structure. PMID- 9991529 TI - Towards memory effects for electrons and phonons on nonrigid lattices. PMID- 9991530 TI - Erratum: Phonon-assisted tunneling in persistent-photocurrent decay PMID- 9991532 TI - Size-dependent surface-plasmon resonances of bare silver particles. PMID- 9991531 TI - Model for the c(2 x 2) structure induced by K on Au(110). PMID- 9991533 TI - Effect of temperature on the dynamics of energetic displacement cascades: A molecular dynamics study. PMID- 9991535 TI - Electronic structure of grain boundaries. PMID- 9991534 TI - Determination of the local order in amorphous cobalt films. PMID- 9991536 TI - Enhanced two-photon photoemission from coldly deposited silver films. PMID- 9991537 TI - Vacancy- and adatom-induced sqrt 3 x sqrt 3 reconstructions of the Si(111) surface. PMID- 9991538 TI - Transient reshaping of intersubband absorption spectra due to hot electrons in a modulation-doped multiple-quantum-well structure. PMID- 9991539 TI - Donors in semiconductors and metastability. PMID- 9991540 TI - Barrier-controlled thermalization in In0.53Ga0.47As/InP quantum wells. PMID- 9991541 TI - Optically detected magnetic resonance of a thermally induced deep center in electron-irradiated silicon. PMID- 9991542 TI - Excitonic transitions in strained-layer InxGa1-xAs/GaAs quantum wells. PMID- 9991544 TI - Persistent photoconductivity and related critical phenomena in Zn0.3Cd0.7Se. PMID- 9991543 TI - Observation of the acceptor-bound exciton confined in narrow GaAs/AlxGa1-xAs quantum wells in photoluminescence excitation. PMID- 9991545 TI - Electronic structure of random semiconductor alloys by the tight-binding linear muffin-tin orbital method. PMID- 9991546 TI - Ballistic transmission in perpendicular quantum point contacts. PMID- 9991547 TI - Electronic structure and conformational statistics of conjugated polymers in solution: A Fermi system with annealed disorder. PMID- 9991548 TI - Sequential resonant tunneling of holes in GaAs-AlAs superlattices. PMID- 9991550 TI - Parabolic-quantum-well self-consistent electronic structure in a longitudinal magnetic field: Subband depopulation. PMID- 9991549 TI - Scanning tunneling microscopy and first-principles theory of the Sn/GaAs(110) surface. PMID- 9991551 TI - Quantum interference in variable range hopping under directional constraints. PMID- 9991552 TI - Interdefect elastic interaction in glass fiber and the theory of tunneling systems. PMID- 9991553 TI - Electrical transport in a quantum wire: Influence of one- and two-body interactions. PMID- 9991554 TI - Charge-density-wave noise propagation in the blue bronzes Rb0.3MoO3 and K0.3MoO3. PMID- 9991555 TI - Optical second-harmonic generation study of oxygen adsorption on a polycrystalline Ag surface. PMID- 9991556 TI - Polarization of carbon electron-momentum density in lithium-graphite intercalation compounds. PMID- 9991557 TI - Formation of local moments on iron in alkali-metal hosts. PMID- 9991558 TI - Resistivity and thermopower studies in the Kondo-lattice Ce3Sn1-xInx system. PMID- 9991559 TI - Local environment of nitrogen in a surface nitride: A low-energy electron diffraction study of Cr(100)-(1 x 1)N. PMID- 9991560 TI - Time-of-flight scattering and recoiling spectrometry. I. Structure of the W(211) surface. PMID- 9991561 TI - Time-of-flight scattering and recoiling spectrometry. II. The structure of oxygen on the W(211) surface. PMID- 9991562 TI - Time-of-flight scattering and recoiling spectrometry. III. The structure of hydrogen on the W(211) surface. PMID- 9991563 TI - Valence-electron excitations in the alkali metals. PMID- 9991564 TI - Chemical bond and electronic states in calcium silicides: Theory and comparison with synchrotron-radiation photoemission. PMID- 9991565 TI - Empty electronic states of calcium silicides: An inverse-photoemission investigation in the ultraviolet photon range. PMID- 9991566 TI - Renormalization of Bloch electrons in coherent light. PMID- 9991567 TI - Reflection of light at a flat interface under normal incidence: A renewed macroscopic description. PMID- 9991568 TI - Angle-resolved inverse photoemission from the Ag(100) surface. PMID- 9991569 TI - Direct experimental identification of the structure of ultrathin films of bcc iron and metastable bcc and fcc cobalt. PMID- 9991570 TI - Multielectron excitations in high-energy photoelectron spectra of CO adsorbed on Ni(100). PMID- 9991571 TI - Reflection electron-energy-loss spectroscopy, x-ray-absorption spectroscopy, and x-ray photoelectron spectroscopy studies of a new type of layer compound CrPS4. PMID- 9991572 TI - Vibrational line shapes of low-frequency adsorbate modes: CO on Pt(111). PMID- 9991573 TI - Electronic-shell effects in small doubly charged lead clusters. PMID- 9991574 TI - Atomic theory of scanning tunneling microscopy. PMID- 9991575 TI - Rigidity of randomly intercalated layered solids. PMID- 9991576 TI - Very-low-temperature electrical resistivity of KRb, KNa, and LiMg alloys. PMID- 9991577 TI - Application of molecular dynamics to the study of hydrogen embrittlement in Ni-Cr Fe alloys. PMID- 9991578 TI - Anharmonic contributions to the Debye-Waller factor: Calculation and application to aluminum. PMID- 9991579 TI - Pseudojellium model for metal clusters. PMID- 9991580 TI - Semiempirical model of covalent bonding in silicon. PMID- 9991581 TI - Substrate temperature dependence of the initial growth mode of SiO2 on Si(100)-(2 x 1) exposed to O2: A photoemission study. PMID- 9991582 TI - Radiation emission by ballistic electrons in semiconducting superlattices. PMID- 9991583 TI - Theory of hole refractions from heterojunctions. PMID- 9991584 TI - Isolated arsenic-antisite defect in GaAs and the properties of EL2. PMID- 9991585 TI - Electric fields and valence-band offsets in n+n PMID- 9991586 TI - Density-functional calculation of effective Coulomb interactions in nonmetallic systems: Application to Mn in CdTe, CdS, and ZnO. PMID- 9991588 TI - Double-resonance-enhanced Raman scattering in laser-recrystallized amorphous silicon film. PMID- 9991587 TI - Growth morphology and electronic structure of the Bi/GaAs(110) interface. PMID- 9991589 TI - Deep levels associated with triplet impurity complexes in GaP. PMID- 9991591 TI - Theory of interactions of surface-optical phonons with surface space-charge waves in doped GaAs. PMID- 9991590 TI - Type-I-type-II transition of GaAs/AlAs short-period superlattices investigated by photoluminescence spectroscopy under hydrostatic pressure. PMID- 9991592 TI - Multimode vibronic model for Fe2+ ions in ZnS. PMID- 9991594 TI - Optical-absorption spectra associated with impurities in a GaAs-(Ga,Al)As quantum well. PMID- 9991593 TI - Kinetics of dopant incorporation using a low-energy antimony ion beam during growth of Si(100) films by molecular-beam epitaxy. PMID- 9991595 TI - Band structure of diluted magnetic Pb1-xMnxTe: Magneto-optical investigations and four-wave-mixing spectroscopy. PMID- 9991596 TI - Electron counting model and its application to island structures on molecular beam epitaxy grown GaAs(001) and ZnSe(001). PMID- 9991597 TI - Nonlocal theory of collective excitations in doped semiconducting films: The effect of depletion and accumulation layers. PMID- 9991599 TI - Mobility of kinks and polarons in conjugated polymers. PMID- 9991598 TI - Predicted power laws for delayed switching of charge-density waves. PMID- 9991600 TI - Electronic structure of red mercuric iodide. PMID- 9991601 TI - Magnetoexciton ground state in a quantum well: A variational and perturbation approach. PMID- 9991602 TI - Coupling between a donor potential and quantum wells: Effect on binding energies. PMID- 9991603 TI - Floppy modes in network glasses. PMID- 9991604 TI - Structural defects in chromium-ion-implanted vitreous silica. PMID- 9991605 TI - Correlation between the activation enthalpy and Kohlrausch exponent for ionic conductivity in oxide glasses. PMID- 9991606 TI - Nuclear quadrupole resonance in the glassy Cu-As-S and Cu-As-Se systems. PMID- 9991607 TI - Renormalized model for the dynamics of the krypton-on-graphite domain-wall lattice. PMID- 9991609 TI - Cohesive properties and vibrational entropy of 3d transition-metal compounds: MX (NaCl) compounds (X=C, N, O, S), complex carbides, and nitrides. PMID- 9991608 TI - Evidence of the orthorhombic D2h18 symmetry of K2CuF4: Phonon-Raman scattering measurements. PMID- 9991610 TI - Near-threshold excitation in light rare-earth compounds: A new interpretation of 3d appearance-potential spectra. PMID- 9991611 TI - Solitonlike structures and their self-similarity in nonlinear Fibonacci multilayered media. PMID- 9991612 TI - Evidence for Fermi-energy pinning relative to either valence or conduction band in Schottky barriers. PMID- 9991614 TI - Evidence for a large valence-band offset at HgTe-CdTe heterojunctions. PMID- 9991613 TI - Neutron excitation of bulk luminescence. PMID- 9991616 TI - Indirect exchange interaction in semimagnetic semiconductors. PMID- 9991615 TI - Anisotropic kinetics and bilayer epitaxial growth of Si(001). PMID- 9991617 TI - Pressure-induced momentum mixing in GaAs-AlAs superlattices. PMID- 9991619 TI - Band theory and the insulating gap in CoO. PMID- 9991618 TI - Temperature-independent behavior of the Hall constant in granular In2O3-x films. PMID- 9991620 TI - Medium-energy ion-beam-induced microstructural modifications in alpha -Fe2O3. PMID- 9991621 TI - Structure of platinum adatom clusters on Pt(100): Experimental observations and embedded-atom-method calculations. PMID- 9991622 TI - Pressure effects on self-diffusion in silicon. PMID- 9991624 TI - Spatial modulation of the Fermi level by coherent illumination of undoped GaAs. PMID- 9991623 TI - Optical and magneto-optical absorption in parabolic quantum wells. PMID- 9991625 TI - Structural resolution of the incommensurate phase of alpha -PbO from x-ray- and neutron-powder-diffraction data. PMID- 9991626 TI - Desorption of positive oxygen ions induced by keV heavy-ion bombardment of transition metals with adsorbed O2 and CO. PMID- 9991627 TI - T2 in incommensurate systems. PMID- 9991629 TI - Effect of thin amorphous layers on channeling in diamond. PMID- 9991628 TI - Reexamination of the local electric field gradients in LiNbO3. PMID- 9991631 TI - Slowing-down time of energetic atoms in solids. PMID- 9991630 TI - Validity of the third-derivative modulation spectroscopy. PMID- 9991632 TI - Determination of excited-state polarizabilities of Cr3+-doped materials by degenerate four-wave mixing. PMID- 9991633 TI - Inelastic neutron scattering study of anharmonic interactions in orthorhombic KNbO3. PMID- 9991634 TI - NMR determination of the nonclassical critical exponents beta and beta -bar in incommensurate Rb2ZnCl4. PMID- 9991635 TI - 87Rb NMR study of the paraelectric-antiferroelectric phase transition in Rb0.52(ND4)0.48D2AsO4. PMID- 9991636 TI - Phase diagram and critical properties of a two-dimensional lattice-gas model of oxygen ordering in YBa2Cu3Oz. PMID- 9991637 TI - Thermodynamic behavior of the heavy-fermion compounds Ce3X (X=Al,In,Sn). PMID- 9991638 TI - Temperature dependence of the tunneling spectrum near a vortex core. PMID- 9991639 TI - Proximity-induced superconducting transition temperature. PMID- 9991640 TI - Cooper-pairing interaction at the edge of an electron energy gap due to antiferromagnetism. PMID- 9991642 TI - Diffusion of lithium in highly oriented pyrolytic graphite at low concentrations and high temperatures. PMID- 9991641 TI - Zero-temperature ordering in two-dimensional frustrated quantum Heisenberg antiferromagnets. PMID- 9991643 TI - Magnetic instability in triplet superconductivity. PMID- 9991644 TI - Electron-electron scattering and phase fluctuations in superconducting films. PMID- 9991645 TI - Theory of critical first sound near the lambda transition of 4He. I. Model and correlation functions. PMID- 9991647 TI - Stability of two-dimensional Fermi liquids against pair fluctuations with large total momentum. PMID- 9991646 TI - Theory of critical first sound near the lambda transition of 4He. II. Attenuation and dispersion for T >= T lambda. PMID- 9991648 TI - Low-temperature specific heat of polycrystalline Ba0.6K0.4BiO3. PMID- 9991650 TI - Three-roton bound states. PMID- 9991649 TI - Magnetic field and temperature dependence of magnetic flux creep in c-axis oriented YBa2Cu3O7 powder. PMID- 9991652 TI - Electrical resistivity and magnetoresistance of CeRu2Si2 under pressure. PMID- 9991651 TI - Quantum fluctuations in a current-biased Josephson junction of small capacitance. PMID- 9991653 TI - Atomistic simulation of dopant substitution in YBa2Cu3O7. PMID- 9991654 TI - Critical-state model for harmonic generation in high-temperature superconductors. PMID- 9991655 TI - Possible superconducting mechanism for high Tc in quasi-one-dimensional multiwire structures. PMID- 9991657 TI - Theory of positron annihilation in superconductors. PMID- 9991656 TI - Tunneling measurement of the energy gaps in the superconductors Y-Ba-Cu-O and Tl Ba-Ca-Cu-O. PMID- 9991658 TI - Antiferromagnetic ordering in superconducting and oxygen-deficient nonsuperconducting RBa2Cu3O7- delta compounds (R=Nd and Sm). PMID- 9991660 TI - Spin-hole polaron of the t-Jz model. PMID- 9991659 TI - High-pressure electrical conductivity measurements in the copper oxides. PMID- 9991661 TI - Temperature-induced magnetism in LaCoO3. PMID- 9991663 TI - Ferrimagnetic Heisenberg chains PMID- 9991662 TI - Thermodynamic properties and phase transitions of the site-bond-correlated Ising model. PMID- 9991665 TI - Long-range interactions in the compressible Heisenberg chain. PMID- 9991664 TI - Absence of localization in certain statically disordered lattices in any spatial dimension. PMID- 9991666 TI - Correlation of phase fluctuations in granular superconductors. PMID- 9991667 TI - Expansion in 1/z for the transition temperature and specific heat of ferromagnets. PMID- 9991668 TI - Memory effects and coexistence of incommensurate and commensurate phases in PMID- 9991670 TI - Ground state of amorphous iron. PMID- 9991669 TI - Low-temperature expansions for the step free energy and facet shape of the simple cubic Ising model. PMID- 9991671 TI - Single-site theory of finite-temperature magnetism in amorphous and liquid alloys. PMID- 9991673 TI - Attractors in quantum Ising models. PMID- 9991672 TI - Ground-state Lennard-Jones and Aziz boson liquids: Perturbation theory and computer experiment. PMID- 9991674 TI - Stability and symmetry of the spin-density-wave state in chromium. PMID- 9991675 TI - Nonlinear development of morphological instabilities in explosive crystallization. PMID- 9991676 TI - Monte Carlo studies of universal critical amplitudes for the three-dimensional Ising model: Correlation length and renormalized coupling. PMID- 9991678 TI - Directional solidification near minimum c PMID- 9991677 TI - Static and dynamic properties of the (FexCr1-x)75P15C10 reentrant-spin-glass amorphous alloy. PMID- 9991679 TI - Influence of surface anisotropy on the magnetization of the Heisenberg ferromagnet. PMID- 9991680 TI - Magnetic properties of PbTe and Pb1-xSnxTe. PMID- 9991682 TI - Propagating modes in quasicrystals. PMID- 9991681 TI - Ground states of infinite-range spin-(1/2 quantum Heisenberg antiferromagnets. PMID- 9991683 TI - High-field magnetoresistance and de Haas-van Alphen effect in antiferromagnetic PrB6 and NdB6. PMID- 9991685 TI - Electronic theory of phase stability in substitutional alloys: The generalized perturbation method versus the Connolly-Williams method. PMID- 9991684 TI - Magnetic properties of iron-rich Fe-Sc glasses. PMID- 9991686 TI - Magnetic susceptibility of vermiculite intercalation compounds with magnetic ions as intercalants. PMID- 9991687 TI - Influence of interface effects on a rare-earth crystal field in iron-rare-earth multilayers. PMID- 9991688 TI - Activated dynamics in a two-dimensional Ising spin glass: Rb2Cu1-xCoxF4. PMID- 9991689 TI - Pure spin-glass resistivity maximum at the "freezing" temperature. PMID- 9991690 TI - Time-differential perturbed-angular-correlation study of phase transitions and molecular motions in K3(Hf,Zr)F7. PMID- 9991691 TI - Effective-field renormalization-group study for the transverse Ising model in a quantum-spin system. PMID- 9991692 TI - Melting of multilayer films: Further studies of a Potts lattice-gas model. PMID- 9991694 TI - Ultrasonic behavior of the heavy-fermion superconductor URu2Si2. PMID- 9991693 TI - Phase transition and high-pressure elastic behavior of copper halides. PMID- 9991695 TI - Comparison of energy distributions of positron- and electron-induced secondary electrons: Implications for slow positron emission mechanisms. PMID- 9991696 TI - Gd3+ exchange interaction as measured by NMR in hydrogen-doped GdBa2Cu3O7H1.55. PMID- 9991697 TI - Chaos in extended linear arrays of Josephson weak links. PMID- 9991698 TI - Modified Lanczos simulation of the localized superconductivity for a chain with interaction and disorder. PMID- 9991699 TI - Surface decomposition of Pb2Sr2(Ca,Y)Cu3O8+ delta at room temperature studied with high-resolution electron microscopy. PMID- 9991700 TI - Reexamination of the specific heat of an extreme type-II classical superconductor versus temperature and magnetic field near Tc. PMID- 9991701 TI - Antiferromagnetic phase transition in high-Tc superconductors. PMID- 9991703 TI - Piezoresistance measurements of YBa2Cu3O7-x showing large magnitude and temporal anomalies between 100 and 300 K. PMID- 9991702 TI - Low-energy excitations in Cu-O-based superconductors with electron-energy-loss spectroscopy. PMID- 9991704 TI - Anisotropic energy gaps in copper oxide superconductors. PMID- 9991706 TI - Some evidence for cation disorder in YBa2Cu3O7. PMID- 9991705 TI - Magnetic and superconducting phase diagram of Bi2Sr3-xYxCu2O8 as determined by muon-spin rotation. PMID- 9991707 TI - Variational ground state of the model of a two-state system coupled with phonons. PMID- 9991709 TI - Free-energy functional in the generalized coherent-potential approximation. PMID- 9991708 TI - Spin-wave velocity and susceptibility for the two-dimensional Heisenberg antiferromagnet. PMID- 9991711 TI - Upper bound on the critical temperature in the n-dimensional Ising model. PMID- 9991710 TI - Dispersive energy transport in disordered solids: Relation to spin-glass relaxation. PMID- 9991713 TI - Specific heat in high magnetic field of kappa -di PMID- 9991712 TI - Comment on "Spin excitations in multilayered ferromagnetic electron gases" PMID- 9991714 TI - Stimulated desorption of atoms from rare-gas monolayers on metal surfaces: Dependence of yields and energy distributions on primary excitations. PMID- 9991715 TI - Variable Hall coefficient in Bi2Sr2CaCu2O8-x across the metal-insulator transition. PMID- 9991716 TI - Hexatic vortex glass in disordered superconductors. PMID- 9991717 TI - Properties of optical features in YBa2Cu3O7- delta. PMID- 9991718 TI - Phonon density of states in Pb2Sr2(Ca,Y)Cu3O8. PMID- 9991719 TI - Effect of Ga substitution on the superconducting properties of the electron-doped system: Nd-Ce-Cu-O. PMID- 9991720 TI - Quantum tunneling and low-voltage resistance in small superconducting tunnel junctions. PMID- 9991722 TI - Electron-phonon interactions in the copper oxides: Implications for the resistivity. PMID- 9991721 TI - Critical phase fluctuations in superconducting wire networks. PMID- 9991723 TI - Spin dynamics of YBa2Cu3O6+x as revealed by NMR. PMID- 9991725 TI - Anisotropy in flux pinning within the c basal plane of Bi2Sr2CaCu2O8+d. PMID- 9991724 TI - Magnetic ordering induced by hydrogen doping of YBa2Cu3O7. PMID- 9991726 TI - Negative magnetoresistance in small superconducting loops and wires. PMID- 9991727 TI - Shift of phonon anomaly with Tc observed in (Y,Er)Ba2Cu3O7- delta by ion channeling. PMID- 9991728 TI - Variation in Tc and carrier concentration in Tl-based superconductors. PMID- 9991729 TI - Tunneling measurements of the energy gap in the high-Tc superconductor Tl2Ba2Ca2Cu3O10+ delta. PMID- 9991730 TI - Synthesis and properties of the 2:4:7 superconductors R2Ba4Cu7O15-x (R=Y,Eu,Gd,Dy,Ho,Er). PMID- 9991731 TI - Phonon modes in corrugated planes. PMID- 9991732 TI - Observation of transitions to spin-slip structures in single-crystal holmium. PMID- 9991733 TI - Critical exponents for ferromagnetic systems with Ruderman-Kittel-Kasuya-Yosida interactions. PMID- 9991734 TI - Numerical study of a model for interface growth. PMID- 9991735 TI - Specific heat of decamethylferrocenium tetracyanoethanide (DMeFc)(TCNE). PMID- 9991736 TI - Phonons and martensitic phase transitions in pure bcc Ti and bcc Zr. PMID- 9991738 TI - Theory of reentrance of spin-density-wave transitions in bis tetramethyltetraselenafulvalenium perchlorate PMID- 9991737 TI - Volume effect at the metamagnetic transition in CeRu2Si2. PMID- 9991739 TI - Variational calculations for the square-lattice quantum antiferromagnet. PMID- 9991740 TI - Polar relaxation mode in pure and iron-doped barium titanate. PMID- 9991741 TI - Dynamical scaling and crossover from algebraic to logarithmic growth in dilute systems. PMID- 9991742 TI - Asymmetry in the hierarchy formalism of the fractional quantum Hall states. PMID- 9991743 TI - Nature of 4f magnetism in Ce1-xLaxPd2Si2. PMID- 9991744 TI - Novel metal-film configuration: Rh on Ag(100). PMID- 9991746 TI - Binding of charged particles in lattice defects. PMID- 9991747 TI - Dielectric response spectrum of a damped one-dimensional double-well oscillator. PMID- 9991745 TI - Low-temperature behavior of Ni3Al alloys near the spin-fluctuator-ferromagnet phase boundary. PMID- 9991748 TI - Calculation of grain-boundary segregation in Ni-Cu alloys. PMID- 9991749 TI - Theory of electron scattering from solids. PMID- 9991750 TI - Coverage dependence of the electronic structure of potassium adatoms on the Si(001)-(2 x 1) surface. PMID- 9991751 TI - Energetics of bcc-fcc lattice deformation in iron. PMID- 9991752 TI - Resonant bound states for simple metal surfaces. PMID- 9991754 TI - Individual-defect electromigration in metal nanobridges. PMID- 9991753 TI - Frequency-dependent conductivity in polycrystalline metals and semiconductors. PMID- 9991755 TI - Relativistic effects in the electron density of states, specific heat, and the electron spectrum of normal metals. PMID- 9991756 TI - Surface polarons near rough surfaces. PMID- 9991757 TI - Quasielastic scattering of neutrons from tunneling hydrogen atoms bound to oxygen impurities in niobium. PMID- 9991759 TI - Localization in near-monolayer films. PMID- 9991758 TI - Charge-density-wave transport above room temperature in a polytype of NbS3. PMID- 9991760 TI - Numerical computation of the piezoresistivity matrix elements for semiconducting barium titanate. PMID- 9991762 TI - Connection of envelope functions at semiconductor heterointerfaces. II. Mixings of Gamma and X valleys in GaAs/AlxGa1-xAs. PMID- 9991761 TI - Connection of envelope functions at semiconductor heterointerfaces. I. Interface matrix calculated in simplest models. PMID- 9991763 TI - Spin-density-wave instability in wide parabolic quantum wells. PMID- 9991764 TI - Interplay of polarizability and ionicity in IV-VI compounds. PMID- 9991765 TI - Hydrogen bonding and diffusion in crystalline silicon. PMID- 9991766 TI - Contribution to the quantum-well exciton linewidth due to the intrasubband scattering by optical phonons in an applied electric field. PMID- 9991767 TI - Hartree-Fock and lowest-order vertex-correction contribution to the direct gap of the semiconductor silicon. PMID- 9991768 TI - Thermal motion of atoms in crystalline silicon: Beyond the Debye theory. PMID- 9991769 TI - Self-diffusion of silicon in polycrystalline Pd2Si in the absence of growth. PMID- 9991770 TI - Temperature dependence of universal conductance fluctuations in narrow mesoscopic Si inversion layers. PMID- 9991772 TI - Three-band transport and cyclotron resonance in alpha -Sn and alpha -Sn1-xGex grown by molecular-beam epitaxy. PMID- 9991771 TI - Transverse magnetotunneling in AlxGa1-xAs capacitors. II. Electron phase changes in resonant Fowler-Nordheim tunneling. PMID- 9991773 TI - Cyclotron resonance in two-dimensional electron-phonon-impurity systems and applications to Si metal-oxide-semiconductor systems. PMID- 9991774 TI - High-resolution low-energy electron-diffraction study of the phase diagram of vicinal Si(111) surfaces. PMID- 9991775 TI - Spin splitting of the conduction band and de Haas-van Alphen effect in Hg1 xFexSe. PMID- 9991776 TI - Optical nutation in polymers irradiated by ultrashort laser pulses. PMID- 9991777 TI - Molecular-dynamics studies of the growth modes and structure of amorphous silicon films via atom deposition. PMID- 9991778 TI - Photoemission proof for a SiO2 island growth mode initiated on the steps of Si(001) during thermal oxidation by O2. PMID- 9991780 TI - Quenching and recovery characteristics of the EL2 defect in GaAs under monochromatic-light illumination. PMID- 9991779 TI - Temperature dependence of the electrical conductivity of AsF5-doped poly(p phenylene vinylene). PMID- 9991781 TI - Positron trapping rates and their temperature dependencies in electron-irradiated silicon. PMID- 9991783 TI - Core-level photoemission investigation of atomic-fluorine adsorption on GaAs(110). PMID- 9991782 TI - Dynamical aspects of luminescence from GaAs-AlAs single quantum wells under hydrostatic pressure. PMID- 9991784 TI - Effects of disorder on electronic structures of a-Si:H and a-SiO2. PMID- 9991785 TI - Resonant tunneling of double-barrier quantum wells affected by interface roughness. PMID- 9991786 TI - Phase of reflection high-energy electron-diffraction intensity oscillations during molecular-beam-epitaxy growth of GaAs(100). PMID- 9991788 TI - Thermally stimulated current in the absence of optical excitation in the annealing of tetracene and pentacene films. PMID- 9991787 TI - Synchrotron photoemission studies of the Sb-passivated Si surfaces: Degenerate doping and bulk band dispersions. PMID- 9991789 TI - Transport, magnetic, and optical properties of electrochemically doped poly(1,4 dimethoxy phenylene vinylene). PMID- 9991790 TI - Inelastic scattering in resonant tunneling. PMID- 9991791 TI - Collective excitations in the accumulation layer of InAs(110): Nonlocal response theory. PMID- 9991792 TI - Excitonic transitions in GaAs-AlxGa1-xAs multiple quantum wells affected by interface roughness. PMID- 9991794 TI - Structure and electrical properties of indium-germanium interfaces. PMID- 9991793 TI - Electronic states of Si(100) reconstructed surfaces. PMID- 9991795 TI - He atom near methane-plated MgO: Interaction and scattering. PMID- 9991796 TI - Phase transition of some ferroelectric niobate crystals with tungsten-bronze structure at low temperatures. PMID- 9991797 TI - Computer-simulation studies of intrinsic defects in LiNbO3 crystals. PMID- 9991798 TI - Random-matrix description of the distribution of mesoscopic conductance. PMID- 9991799 TI - Atomic mean-square displacement of a solid: Results for a long-range potential from the Green's-function method. PMID- 9991800 TI - Transport model for hot positrons in layered structures. PMID- 9991801 TI - Band filling and structural stability of cubic trialuminides: YAl3, ZrAl3, and NbAl3. PMID- 9991802 TI - Evaluation of the interface states between alternating trans-polyacetylene and polyethylene quasi-one-dimensional chains. PMID- 9991804 TI - Energy-momentum relation for polarons in quantum-well wires. PMID- 9991803 TI - First-principles calculation of the elastic constants of AlAs. PMID- 9991805 TI - Anisotropy of optical absorption in wurtzite-phase Zn0.85Mn0.15S. PMID- 9991806 TI - Phases of the multiple quantum well in a strong magnetic field: Possibility of irrational charge. PMID- 9991807 TI - Effect of alloy disorder on the deep levels produced by the anion vacancy in GaAs1-xPx. PMID- 9991808 TI - Dimer strings, anisotropic growth, and persistent layer-by-layer epitaxy. PMID- 9991809 TI - Far-infrared absorption in potassium iodide. PMID- 9991810 TI - Comment on "Fluctuations of the hot-carrier state-occupancy function in homogeneous semiconductors" PMID- 9991811 TI - Reply to "Comment on 'Fluctuations of the hot-carrier state-occupancy function in homogeneous semiconductors' " PMID- 9991812 TI - Erratum: Optical studies of bonding in coevaporated amorphous silicon-tin alloys PMID- 9991813 TI - Scanning tunneling microscopy of the charge-density wave in orthorhombic TaS3. PMID- 9991814 TI - Theory of transition from the tunneling regime to point contact in scanning tunneling microscopy. PMID- 9991815 TI - Epitaxial growth of Ag on Au(111) studied by scanning tunneling microscopy. PMID- 9991816 TI - Microscopic theory of surface phonons in Al(100): Mechanisms for the anomalous behavior of the dispersion curves for large wave vectors. PMID- 9991818 TI - Low-velocity antiproton stopping power. PMID- 9991817 TI - Exchange-induced spin polarization of conduction electrons in paramagnetic metals. PMID- 9991819 TI - Femtosecond laser melting of graphite. PMID- 9991820 TI - Method for the calculation of scanning tunneling microscope images and spectra. PMID- 9991821 TI - Optical reflectance of liquid mercury. PMID- 9991823 TI - Self-consistent polaron scattering rates in quasi-one-dimensional structures. PMID- 9991822 TI - Protonation process of pernigraniline: A theoretical investigation. PMID- 9991824 TI - Bound-to-bound transitions at neutral zinc in silicon: Effective-mass-like states and hole-hole interaction. PMID- 9991825 TI - d states, exchange splitting, and Mn electronic configuration in Cd1-xMnxTe. PMID- 9991826 TI - Transport anomalies in the lowest Landau level of two-dimensional electrons at half-filling. PMID- 9991827 TI - Fermi-edge singularity in heavily doped GaAs multiple quantum wells. PMID- 9991828 TI - Collective cyclotron resonance in a quasi-three-dimensional electron gas. PMID- 9991829 TI - Characterization of microvoids in device-quality hydrogenated amorphous silicon by small-angle x-ray scattering and infrared measurements. PMID- 9991830 TI - Optical constants of cubic boron nitride. PMID- 9991831 TI - Low-temperature photoluminescence spectrum of amorphous semiconductors. PMID- 9991832 TI - Level crossing and the fractional quantum Hall effect. PMID- 9991833 TI - Search for thermally generated monovacancies in silicon using monoenergetic positrons. PMID- 9991834 TI - Collective electronic oscillations in slender structures at finite temperatures. PMID- 9991835 TI - Relaxed structure of two-atom crystals with surfaces. PMID- 9991836 TI - Short-range-order effects in CuxPt1-x. PMID- 9991837 TI - Neutron powder-diffraction studies of lithium, sodium, and potassium metal. PMID- 9991838 TI - Accuracy of time-dependent properties in electronic-structure calculations using a fictitious Lagrangian. PMID- 9991839 TI - Simplified method for fully relativistic spin-polarized density-functional calculations. PMID- 9991840 TI - Band structure, photoelectron spectroscopy, and transport properties of SnTaS2. PMID- 9991842 TI - van der Waals force between a spherical tip and a solid surface. PMID- 9991841 TI - Effect of impurities on electron motion in two dimensions in a strong magnetic field. PMID- 9991843 TI - Ab initio method for calculating response functions in transition metals. PMID- 9991844 TI - Surface models for perpendicular ambipolar transport in kinetic and hydrodynamic theories. PMID- 9991845 TI - Interstitial-electron model for lattice dynamics in fcc metals. PMID- 9991846 TI - Layer Korringa-Kohn-Rostoker technique for surface and interface electronic properties. PMID- 9991847 TI - Layer Korringa-Kohn-Rostoker theory for close-spaced planes of atoms. PMID- 9991848 TI - Effect of phason strain on the transition of an octagonal quasicrystal to a beta Mn-type structure. PMID- 9991850 TI - Tight-binding coherent-potential approximation including off-diagonal disorder. PMID- 9991849 TI - Vibrational and electronic spectra of one-dimensional organic charge-transfer crystals: Model for a tetramerized cluster structure. PMID- 9991851 TI - Dynamics of gap solitons. PMID- 9991852 TI - Diffusion and fluctuations in a nonequilibrium electron gas with electron electron collisions. PMID- 9991853 TI - Dynamic structure of electrons in Be metal by inelastic x-ray scattering spectroscopy. PMID- 9991854 TI - Structure of oriented V2O5 gel studied by polarized x-ray-absorption spectroscopy at the vanadium K edge. PMID- 9991855 TI - Kinetic equation for strongly disordered systems: Noninteracting electrons. PMID- 9991856 TI - Solution of Schrodinger's equation for large systems. PMID- 9991857 TI - Electronic response in a one-dimensional nonlinear lattice. PMID- 9991859 TI - Transient characteristics of excitons bound at hole-attractive isoelectronic centers in GaP. PMID- 9991858 TI - Missing-row reconstruction of Ag(110) induced by a 2 x 1) oxygen overlayer. PMID- 9991860 TI - Excitons in one-phonon resonant Raman scattering: Frohlich and interference effects. PMID- 9991861 TI - Electron-hole plasma dynamics in CdTe in the picosecond regime. PMID- 9991862 TI - Electronic and optical properties of CeS under pressure. PMID- 9991863 TI - Emission of circularly polarized recombination radiation from p-doped GaAs and GaAs0.62P0.38 under the impact of polarized electrons. PMID- 9991864 TI - Lattice-dynamical study of layered silicates. PMID- 9991865 TI - Electronic structure of the InAs-GaSb superlattice studied by the renormalization method. PMID- 9991867 TI - Effects of d bands on semiconductor sp Hamiltonians. PMID- 9991866 TI - Spectroscopic study of the effect of confinement on shallow acceptor states in GaAs/AlxGa1-xAs quantum wells. PMID- 9991868 TI - Resonance Raman scattering in HgTe: TO-phonon and forbidden-LO-phonon cross section near the E1 gap. PMID- 9991869 TI - Excitonic and nonlinear-optical properties of dielectric quantum-well structures. PMID- 9991870 TI - Correlation functions of hot electrons in semiconductors. PMID- 9991872 TI - Effect of uniaxial stress on local vibrational modes of hydrogen in ion-implanted silicon. PMID- 9991871 TI - Relaxation of photoexcited electron-hole plasma in quantum wells. PMID- 9991873 TI - Correlation between electronic structure and local ordering in hydrogenated amorphous silicon. PMID- 9991874 TI - Linear and nonlinear optical response of spherical anisotropic semiconductor microcrystallites. PMID- 9991875 TI - Real-space-indirect resonant Raman scattering in type-II heterostructures. PMID- 9991876 TI - Generalized Drude approach to the conductivity relaxation time due to electron hole collisions in optically excited semiconductors. PMID- 9991877 TI - Effects of spin-orbit scattering on hopping magnetoconductivity. PMID- 9991878 TI - Gap states of charged solitons in polyacetylene. PMID- 9991879 TI - Structural phase transitions in InSb to 66 GPa. PMID- 9991880 TI - Analytic solutions of the effective-mass equation in strained Si-Si1-xGex heterostructures applied to resonant tunneling. PMID- 9991882 TI - Novel recurrent approach to the generalized Su-Schrieffer-Heeger Hamiltonians. PMID- 9991881 TI - Si(111) 2 x 1 surface core-level shifts investigated by use of Ge overlayer. PMID- 9991883 TI - Photodarkening, structural instabilities, and crystallization of glassy As2Se3 induced by laser irradiation. PMID- 9991885 TI - Molecular motion in solid H2 at high pressures. PMID- 9991884 TI - Infrared study of Rb0.3MoO3. PMID- 9991886 TI - Resistivity measurements on potassium cooled in strong magnetic fields. PMID- 9991888 TI - Collective resonance frequencies of metal cluster ions. PMID- 9991887 TI - Role of defects for the spontaneous vitrification of beta -(Cr,Ti). PMID- 9991889 TI - Size manipulation of metal particles with laser light. PMID- 9991890 TI - Macroscopic effect of the compensation on the binding energy of an electron bound to a donor in an n-type quantum well. PMID- 9991891 TI - Pressure dependence of the band gaps of semiconductors. PMID- 9991892 TI - Radiative recombination across the E0+ Delta 0 band gap in CdTe. PMID- 9991893 TI - Positron states at vacancy-impurity pairs in semiconductors. PMID- 9991894 TI - Vibrational overtone absorption of interfacial hydrogen in porous Vycor glass. PMID- 9991895 TI - Periodic defect wall structures in irradiated solids: The spectrum of stationary solutions. PMID- 9991896 TI - Ballistic electronic conductance of an orifice. PMID- 9991897 TI - Surface-plasmon dispersion relation on n-type GaAs: A comparison of local and nonlocal response. PMID- 9991898 TI - Synchrotron-radiation study of the satellites in Ni L3-M4,5M4,5 Auger spectra. PMID- 9991900 TI - Structure of lithium-doped polyacetylene. PMID- 9991899 TI - Metastable state of the EL2 defect in GaAs. PMID- 9991901 TI - Elastic energies and order in epitaxial Si-Ge alloys. PMID- 9991902 TI - Universal dopant and defect equilibration kinetics in n-type a-Si:H. PMID- 9991903 TI - Dressed exciton versus dressed atom: The space-dimension dependence. PMID- 9991905 TI - Alkali-metal-induced interface resonant state on a semiconductor surface. PMID- 9991904 TI - Violation of the integral quantum Hall effect: Influence of backscattering and the role of voltage contacts. PMID- 9991906 TI - Dimensional excitations in narrow electron inversion channels on Si. PMID- 9991907 TI - Location of hydrogen adsorbed on palladium (111) studied by low-energy electron diffraction. PMID- 9991908 TI - Resistance noise in amorphous Ni-Zr: Hydrogen diffusion and universal conductance fluctuations. PMID- 9991909 TI - Hydrogen vibration and phonon dispersion in alpha -ScDx systems. PMID- 9991910 TI - Cluster interactions and physical properties of Al-transition-metal alloys. PMID- 9991911 TI - Crystal-melt and melt-vapor interfaces of nickel. PMID- 9991913 TI - Electronic structure in the Al-Mn alloy crystalline analog of quasicrystals. PMID- 9991912 TI - Exchange-excited f-f transitions in the electron-energy-loss spectra of rare earth metals. PMID- 9991914 TI - Multiple-scattering Green-function method for space-filling cell potentials. PMID- 9991916 TI - Magnetic ordering of thin Gd overlayers. PMID- 9991915 TI - Charge-exchange reactions in metal clusters: Role of magic numbers. PMID- 9991918 TI - Simplified pseudopotential expansion theory for Al-Li alloys. PMID- 9991917 TI - Surface-phason modes in incommensurate crystals. PMID- 9991920 TI - X-ray diffraction data for graphite to 20 GPa. PMID- 9991919 TI - Evolution and splitting of plasmon bands in metallic superlattices. PMID- 9991921 TI - Time-differential perturbed-angular-correlation study of alpha -phase and icosahedral Al-Mn-Si alloys. PMID- 9991922 TI - Hydrogen uptake kinetics on niobium surfaces. PMID- 9991923 TI - Temperature dependence of fractal formation in ion-implanted a-Ge/Au bilayer thin films. PMID- 9991924 TI - Doubly and triply resonant Raman scattering via electron-two-phonon and impurity induced Frohlich interactions in uniaxially stressed GaAs. PMID- 9991925 TI - Cluster calculations of the Si(111) 7 x 7 dimer-adatom-stacking-fault structure. PMID- 9991926 TI - Stress splitting of the zero-phonon line of the (AsGa-Asi) defect pair in GaAs: Significance for the identity of EL2. PMID- 9991927 TI - Auger regeneration of the EL2 defect induced by the Debye tail in the space charge region of a junction: Application to the so-called "optical regeneration" PMID- 9991928 TI - Conduction-band offsets in pseudomorphic InxGa1-xAs/Al0.2Ga0.8As quantum wells (0.07 <= x <= 0.18) measured by deep-level transient spectroscopy. PMID- 9991929 TI - Optical properties of ion-implanted GaAs: The observation of finite-size effects in GaAs microcrystals. PMID- 9991931 TI - Energy spectrum of a layered system in a strong magnetic field. PMID- 9991930 TI - Evaluation of some scattering times for electrons in unbiased and biased single- and multiple-quantum-well structures. PMID- 9991933 TI - Transfer-matrix method for the complex band structure of superlattices. PMID- 9991934 TI - Cluster molecular-orbital calculations on germanium adsorbed on Si(111) surfaces. PMID- 9991932 TI - Perpendicular transport of photoexcited electrons and holes in GaAs/AlAs short period superlattices: Barrier-thickness and temperature dependence. PMID- 9991936 TI - Initial stages of oxygen adsorption on Si(111). II. The molecular precursor. PMID- 9991935 TI - Acoustic attenuation and optical-absorption effects on light scattering by acoustic phonons in superlattices. PMID- 9991937 TI - Evolution of empty-state bands for Bi/GaAs(110): From Bi zigzag chains to ordered overlayers. PMID- 9991938 TI - Mixed-crystal lattice dynamics of HfxTi1-xSe2. PMID- 9991939 TI - Atomic arrangement of spontaneously ordered Al0.5In0.5P/GaAs. PMID- 9991940 TI - Preparation, structure, dynamics, and energetics of amorphous silicon: A molecular-dynamics study. PMID- 9991941 TI - Electronic surface states in semiconductor superlattices: The case of a triple constituent superlattice. PMID- 9991942 TI - Optical-absorption studies of wurtzite-phase Zn1-xMnxSe. PMID- 9991944 TI - Folded phonons in (GaAs)n1(AlAs)n2 superlattices grown along the PMID- 9991943 TI - Optical transitions of different Mn-ion pairs in ZnS. PMID- 9991945 TI - Raman scattering of & superlattices grown along the PMID- 9991947 TI - Analysis of the superhyperfine structure and the g tensor of defects in amorphous silicon. PMID- 9991946 TI - dc conductivity of arsenic-doped silicon near the metal-insulator transition. PMID- 9991948 TI - Resonant Raman scattering by LO phonons in AlxGa1-xAs (0.2Mn PMID- 9992086 TI - X-band microwave study of CdCr2Se4 doped with In and Cd1-xInxCr2Se4 thin films. PMID- 9992088 TI - Equation of state for 3He submonolayers physisorbed in 4He-film surface states: Thermal Hartree-Fock approximation. PMID- 9992090 TI - Magnetic field dependence of the Josephson current in two-dimensional tunnel junctions. PMID- 9992089 TI - Dissipative quantum tunneling: A variational principle for phase shifts. PMID- 9992091 TI - Relaxation mechanism of ultrasonic attenuation in Ho-rich Er1-xHoxRh4B4. PMID- 9992092 TI - Sudden theory for tunneling in dissipative systems. PMID- 9992093 TI - Ultra-small-capacitance Josephson junction: Inductive coupling to a voltage source. PMID- 9992094 TI - Charging corrections to the Josephson Hamiltonian. PMID- 9992095 TI - Increased flux pinning upon thermal-neutron irradiation of uranium-doped YBa2Cu3O7. PMID- 9992096 TI - Phonon anomalies and range of superconducting energy gaps from infrared studies of YBa2Cu3O7- delta. PMID- 9992097 TI - Effective interactions in an oxygen-hole metal. PMID- 9992098 TI - Structure of the interstitial oxygen defect in La2NiO4+ delta. PMID- 9992099 TI - Static Coulomb model for high-temperature superconductivity. PMID- 9992100 TI - Equivalence between the nonlinear sigma model and the spin-(1/2 antiferromagnetic Heisenberg model: Spin correlations in La2CuO4. PMID- 9992101 TI - Oxygen hole symmetry and banding in cuprate superconductors. PMID- 9992103 TI - Lattice dynamics of La2NiO4. PMID- 9992102 TI - Inelastic light scattering enhancement near an electronic excitation at 2 eV in La2CuO4+y. PMID- 9992104 TI - Comparison of effective models for CuO2 layers in oxide superconductors. PMID- 9992106 TI - Superconductor-to-nonsuperconductor transition in (La1-xSrx)2CuO4 as investigated by transport and magnetic measurements. PMID- 9992105 TI - Crystallization of metal-oxide glasses in Bi-Sr-Ca-Cu-O systems. PMID- 9992107 TI - Broken symmetry and (1/2 statistics of spinons in (2+1)-dimensional antiferromagnets. PMID- 9992108 TI - Large, dispersive photoelectron Fermi edge and the electronic structure of YBa2Cu3O6.9 single crystals measured at 20 K. PMID- 9992109 TI - Nonuniversal critical dynamics on the Fibonacci-chain quasicrystal. PMID- 9992110 TI - Spontaneous emission of radiation from a discrete sine-Gordon kink. PMID- 9992111 TI - Fermi surface of the one-dimensional Hubbard model. PMID- 9992112 TI - Statistical thermodynamics of highly defective compounds. PMID- 9992113 TI - Statistical thermodynamic study of nonstoichiometric titanium monoxide: Determination of formation and interaction energies of vacancies. PMID- 9992114 TI - Heat capacity and transport measurements in sputtered niobium-zirconium multilayers. PMID- 9992115 TI - Effect of surface roughening on chaos in yttrium-iron-garnet spheres. PMID- 9992116 TI - 79Br nuclear-quadrupole-resonance line shape and Raman-induced spin-lattice relaxation in the incommensurate phase of beta -ThBr4. PMID- 9992117 TI - Numerical study of multitime scaling in a solid system undergoing phase separation. PMID- 9992118 TI - Magnetic susceptibility of Mn2+ ions in MgO and evidence of clustering. PMID- 9992120 TI - Quantum hard rods: Critical behavior and conformal invariance. PMID- 9992119 TI - Metallic ferromagnetism in a single-band model. PMID- 9992121 TI - Refractive-index measurements of dense helium up to 16 GPa at T=298 K: Analysis of its thermodynamic and electronic properties. PMID- 9992122 TI - Magnetic susceptibility of Zn1-xCoxS and Zn1-xCoxSe alloys. PMID- 9992123 TI - Diffusing-wave spectroscopy and multiple scattering of light in correlated random media. PMID- 9992124 TI - Quantum Monte Carlo calculation of the thermodynamic functions of a Lennard-Jones chain of atoms. PMID- 9992125 TI - Heat capacity, magnetic susceptibility, and electric resistivity of the equiatomic ternary compound CePdSn. PMID- 9992126 TI - Edge critical exponent for the three-dimensional Ising model by Monte Carlo simulations. PMID- 9992128 TI - Soft-mode transition in the ferroelastic crystal K2Hg(CN)4. PMID- 9992129 TI - High-pressure investigation of Hg0.91Mn0.09Te. PMID- 9992127 TI - Spin correlation function of the S=1 antiferromagnetic Heisenberg chain by the large-cluster-decomposition Monte Carlo method. PMID- 9992130 TI - Neutron diffuse scattering study of the ferromagnetism in Pt-10 at. % Fe. PMID- 9992131 TI - Theory of the two-step spin conversion induced by the cooperative molecular distortions in spin-crossover compounds. PMID- 9992133 TI - Self-consistent phonon approach to thermal vibrations in model small clusters. PMID- 9992132 TI - Influence of rough surfaces on electrolytic conduction in porous media. PMID- 9992135 TI - Scaling in random-bond Ising models. PMID- 9992134 TI - Compressibility and density response function in disordered systems. PMID- 9992137 TI - Modified spin-wave theory of a square-lattice antiferromagnet. PMID- 9992136 TI - Path-integral treatment of the liquid-gas transition: From simple fluids to microemulsions. PMID- 9992138 TI - Crossover theory for disordered ferromagnets. PMID- 9992139 TI - Critical behavior of p(2 x 2) oxygen on Ru(001): An example of four-state Potts critical exponents. PMID- 9992140 TI - 35Cl nuclear quadrupole resonance study in 4,4'-dichlorobiphenyl sulphone: A possible incommensurate system. PMID- 9992141 TI - Surface phase transition and tricritical point of a semi-infinite Ising model with diluted spins on a surface. PMID- 9992142 TI - Trapping model for thermal and nonthermal positrons in metals. PMID- 9992143 TI - Atomic migration in CuGa0.1Fe1.9O4. PMID- 9992144 TI - Low-field microwave absorption and Cr3+-Cr3+ pair transitions in highly doped yttrium aluminum garnet. PMID- 9992145 TI - Search for aftereffects in tin oxide films. PMID- 9992146 TI - Fractal dimension for the roughness of a film surface. PMID- 9992147 TI - Modulated microwave absorption in superconducting mercury. PMID- 9992148 TI - Magnetic properties of the superconducting "superoxide" La2CuO4+ delta. PMID- 9992149 TI - Strong-coupling corrections in high-Tc superconductors. PMID- 9992150 TI - Temperature-dependent phonon lifetime of the 428-cm-1 Raman line in La2CuO4+y. PMID- 9992151 TI - Superconducting (1:1:2:2)-type layered cuprates of the formula TlCA1-xLxSr2Cu2Oy (L=Y or rare-earth element). PMID- 9992152 TI - New family of layered copper oxide compounds with ordered cations: Prospective high-temperature superconductors. PMID- 9992154 TI - Density of states of quasi-one-dimensional charge-density and spin-density waves. PMID- 9992153 TI - Anisotropic 63Cu nuclear relaxation in magnetically oriented powdered samples of YBa2Cu3O7. PMID- 9992155 TI - Test of the coherent-anisotropy-field approximation for a lattice model of a random-axis ferromagnet in a high magnetic field. PMID- 9992156 TI - Novel transition between critical and localized states in a one-dimensional quasiperiodic system. PMID- 9992157 TI - Finite-size effects at first-order phase transitions observed in adsorbed oxygen films. PMID- 9992158 TI - Isothermal phase diagrams (Hp,P) for metamagnetic Ni(NO3)2 PMID- 9992159 TI - Ordering in ferromagnets with random anisotropy including magnetostatic coupling. PMID- 9992160 TI - Comment on "Ground state of the strong-coupling Hubbard Hamiltonian: A numerical diagonalization study" PMID- 9992161 TI - Reply to "Comment on 'Ground state of the strong-coupling Hubbard Hamiltonian: A numerical diagonalization study' " PMID- 9992163 TI - Reply to "Comment on 'Weak localization and the conductivity of nondegenerate electrons' " PMID- 9992162 TI - Comment on "Weak localization and the conductivity of nondegenerate electrons" PMID- 9992164 TI - Erratum: "New criticality in quantum models with pair interactions decaying as power law" PMID- 9992165 TI - Replica symmetry in a one-dimensional spin-glass model with long-range interactions. PMID- 9992166 TI - Low-temperature spin reorientation and Co hyperfine fields in Nd2Co14B studied by NMR. PMID- 9992167 TI - Mean-field theory for the t-J model. PMID- 9992168 TI - Specific heat of UPt3 at the metamagnetic phase transition. PMID- 9992169 TI - Effect of Ce doping on the Cu charge in the electron superconductor Nd2-xCexCuO4. PMID- 9992170 TI - Electronic Hamiltonian and antiferromagnetic interactions in La2CuO4. PMID- 9992171 TI - Single-crystal neutron-diffraction investigation of the magnetic ordering of the high-temperature superconductor ErBa2Cu3O7- delta. PMID- 9992172 TI - Fractal formation of a Y-Ba-Cu-O thin film on SrTiO3. PMID- 9992174 TI - Raman scattering from superconducting gap excitations in Tl2Ca2Ba2Cu3O10 single crystals. PMID- 9992173 TI - Flux phases in two-dimensional tight-binding models. PMID- 9992175 TI - Grain-boundary effects on the resistivity of zinc-doped Y-Ba-Cu-O. PMID- 9992176 TI - Calculation of Raman- and infrared-active modes of Tl2CaBa2Cu2O8. PMID- 9992177 TI - Spectroscopic, transport, and magnetic results on the Nd2-xAx4+CuO4- delta systems (A=Ce and Th). PMID- 9992179 TI - Raman scattering spectra of a superconducting Pb2Sr2Y0.75Ca0.25Cu3O8+ delta single crystal. PMID- 9992180 TI - Ultraviolet photoemission study of single-crystal BaPb1-xBixO3. PMID- 9992178 TI - Ba 4d core-level spectroscopy in the YBa2Cu3O6.9 high-Tc superconductor: Existence of a surface-shifted component. PMID- 9992181 TI - Electron-phonon coupling in superconducting Ba0.6K0.4BiO3: A Raman scattering study. PMID- 9992182 TI - Systematics of transport critical-current-density hysteresis in polycrystalline Y Ba-Cu-O. PMID- 9992183 TI - Jastrow states for highly correlated two-dimensional Hubbard fermions. PMID- 9992185 TI - Magnetization of imperfect superconducting grains. PMID- 9992184 TI - Magnetic field penetration depth of polycrystalline (Y,Gd)Ba2Cu3O7, grain-aligned YBa2Cu3O7, and single-crystal Bi2Sr2CaCu2O8. PMID- 9992186 TI - Surface structural and electronic properties of cleaved single crystals of Bi2.15Sr1.7CaCu2O8+ delta compounds: A scanning tunneling microscopy study. PMID- 9992187 TI - Magnons and phonons in Nd2CuO4. PMID- 9992188 TI - Superconducting properties of the Ba1-xRbxBiO3 system. PMID- 9992190 TI - Effective holon-holon interaction in the resonating-valence-bond state. PMID- 9992189 TI - Thermoelectric power and thermal conductivity of neutron-irradiated YBa2Cu3O7- delta. PMID- 9992192 TI - Sine-Gordon theory of the non-Neel phase of two-dimensional quantum antiferromagnets. PMID- 9992191 TI - Scaling properties of the irreversible magnetization curves of high-temperature superconductors. PMID- 9992193 TI - Hole motion in an S=1 chain. PMID- 9992194 TI - Degenerate spin-boson system. PMID- 9992195 TI - High-density structures and phase transition in an ionic model of H2O ice. PMID- 9992196 TI - Instability of the Nagaoka state with more than one hole. PMID- 9992197 TI - Off-diagonal long-range order in Laughlin's states for particles obeying fractional statistics. PMID- 9992199 TI - Spin-1 XXZ model on the square lattice. PMID- 9992198 TI - Spin-wave results for the triangular Heisenberg antiferromagnet. PMID- 9992200 TI - Discontinuously branching tree morphology induced at the NaCl/AgCo interface by ion irradiation. PMID- 9992201 TI - Green-function Monte Carlo study of quantum antiferromagnets. PMID- 9992202 TI - Thermal line broadening in small metal clusters. PMID- 9992204 TI - Full-potential linear augmented-Slater-type-orbital method. PMID- 9992203 TI - Interpretation of the linear coefficient of surface-plasmon dispersion. PMID- 9992205 TI - Coverage-dependent shifts of s and p resonances of alkali metals chemisorbed on Al(111). PMID- 9992206 TI - Structures of PMID- 9992207 TI - Structures of PMID- 9992209 TI - Core-level shifts in ionic KCN multilayers: A synchrotron-radiation and Penning spectroscopy study of K and CN on Pd(111) and Pd(100). PMID- 9992208 TI - Structural and electronic structural properties of ordered LiAl compounds. PMID- 9992210 TI - Thermoelectric power and conductivity of heterogeneous conducting polymers. PMID- 9992211 TI - Occupied electronic structure of Au and Ag on Ge(111). PMID- 9992212 TI - Anisotropic tight-binding model for localization. PMID- 9992213 TI - Molecular-dynamics study of lattice-defect-nucleated melting in silicon. PMID- 9992214 TI - Molecular-dynamics study of lattice-defect-nucleated melting in metals using an embedded-atom-method potential. PMID- 9992215 TI - Bulk and surface vibrational modes in NiAl. PMID- 9992216 TI - Exact analytical solution of the internal friction associated with a geometric kink chain oscillating in an atmosphere of paraelastic interstitials and decorated by a dragging point defect. PMID- 9992217 TI - Molecular cluster model for magnetic iron. PMID- 9992218 TI - Hall effect of the charge-density-wave system (NbSe4)10/3I. PMID- 9992219 TI - Electronic states of a quasiperiodic lattice with long-range electron transfer. PMID- 9992220 TI - Magnetotransport of an electron-hole plasma in a GaAs quantum well. PMID- 9992221 TI - Pulse distortion in GaAs quantum wells studied by a light-gating technique. PMID- 9992222 TI - Envelope-function formalism for phonons in heterostructures. PMID- 9992223 TI - Temperature effects for Ti/GaAs(110) interface formation involving cluster and atom deposition. PMID- 9992225 TI - Random fields and Wigner crystallization. PMID- 9992224 TI - Electrical and optical characterization of metastable deep-level defects in GaAs. PMID- 9992227 TI - Dynamical conductivity of a quantum-wire superlattice. PMID- 9992226 TI - Electronic states and optical transitions in modulation-doped n-type GaxIn1 xAs/AlxIn1-xAs multiple quantum wells. PMID- 9992228 TI - Entropy of migration for atomic hopping. PMID- 9992229 TI - Metastable electron-paramagnetic-resonance spectra in the charge-density-wave state of pure and V-doped blue bronzes A0.3MoO3 (A=K, Rb). PMID- 9992230 TI - Hot phonons in InAs observed via picosecond free-carrier absorption. PMID- 9992231 TI - Generalized norm-conserving pseudopotentials. PMID- 9992232 TI - Folded-acoustic phonons in GaAs/AlAs thin-layer superlattices under high pressure. PMID- 9992233 TI - WSe2: Optical and electrical properties as related to surface passivation of recombination centers. PMID- 9992235 TI - Photoluminescence study of undoped and modulation-doped pseudomorphic AlyGa1 yAs/InxGa1-xAS/AlyGa1-yAs single quantum wells. PMID- 9992234 TI - Effect of nonparabolicity on the conduction-electron spin resonance in cubic semiconductors. PMID- 9992236 TI - Metal submonolayers on Hg-Zn-Te alloys: Electrochemical and electrolyte electroreflectance studies. PMID- 9992237 TI - Direct measurement of resonant and nonresonant tunneling times in asymmetric coupled quantum wells. PMID- 9992238 TI - Magnetotransport studies on the metallic side of the metal-insulator transition in PbTe. PMID- 9992239 TI - Phonon properties of GaAs/AlAs superlattice grown along the PMID- 9992240 TI - Band structure and optical properties of Si-Si1-xGex superlattices. PMID- 9992241 TI - Phonon dispersion curves of GaAs-AlAs superlattices grown in the PMID- 9992242 TI - Optical studies of the quasi-one-dimensional charge-density-wave state in PMID- 9992244 TI - Static polarizability of interacting pi electrons in conjugated polymers. PMID- 9992243 TI - Quantum-well states under biaxial compression and tension. PMID- 9992245 TI - Quantum theory of electronic properties in doped semiconductors by an extension of the method of the bent-band theory. PMID- 9992246 TI - Photoexcitation in Durham-route polyacetylene: Self-localization and charge transport. PMID- 9992247 TI - Structure determination of the CoSi2(111) surface using medium-energy ion scattering. PMID- 9992248 TI - Monte Carlo study of the liquid CdTe surface. PMID- 9992249 TI - Imperfections in amorphous chalcogenides. IV. A model of electrical conduction processes in amorphous and crystalline In2Se3. PMID- 9992250 TI - Photon-stimulated desorption of fluorine from silicon via substrate core excitations. PMID- 9992252 TI - Berry's phase in the effective-Hamiltonian theory of solids. PMID- 9992251 TI - Electric field dependence of exciton oscillator strengths in GaAs-AlxGa1-xAs quantum wells studied by photocurrent spectroscopy. PMID- 9992253 TI - Evaluation of quasiparticle energies for semiconductors without inversion symmetry. PMID- 9992254 TI - Tunneling plasmon excitations in quasi-zero-dimensional superlattices composed of quantum dots. PMID- 9992255 TI - Reduced intrachain spin diffusion in trans-polyacetylene due to sp3 orbital defects. PMID- 9992257 TI - Electron-electron scattering: Collision integral and relaxation rate. PMID- 9992256 TI - Optical spectroscopy of extrinsic recombinations in gallium selenide. PMID- 9992258 TI - First-principles calculation of alloy phase diagrams: The renormalized interaction approach. PMID- 9992260 TI - Possibility of off-center-exciton formation in BaFBr. PMID- 9992259 TI - Nonequilibrium spin polarization of F centers in KBr and KI under saturated optical pumping with modulated circular polarization. PMID- 9992261 TI - Optical properties of vanadium silicide polycrystalline films. PMID- 9992262 TI - Thermal properties of boron and borides. PMID- 9992263 TI - Dielectric anomaly of porous media: The role of multipolar interactions. PMID- 9992264 TI - Defects and mass transport in rutile-structured fluorides. I. Experiment. PMID- 9992265 TI - Defects and mass transport in rutile-structured fluorides. II. Computer simulation. PMID- 9992266 TI - Far-infrared optical investigations on quasi-one-dimensional halogen-bridged mixed-valence compounds. PMID- 9992267 TI - van der Waals forces in a Monte Carlo and lattice-dynamics study of the thermal and elastic properties of a rigid-ion model of potassium chloride. PMID- 9992268 TI - Electronic properties of ionic insulators on semiconductor surfaces: Alkali fluorides on GaAs(100). PMID- 9992269 TI - X-ray diffraction study of the lattice deformation due to 3He bubble formation in a tantalum tritide. PMID- 9992271 TI - Structural transitions in fluorine-based perovskites: A molecular-dynamics study of KMnF3. PMID- 9992270 TI - Angle-resolved extended energy-loss fine structure on CO2: Analogies and differences with photoabsorption. PMID- 9992272 TI - Determination of the whole set of elastic constants of a polymeric Langmuir Blodgett film by Brillouin spectroscopy. PMID- 9992273 TI - Analysis of the absorption spectrum of ruby at high pressures. PMID- 9992274 TI - Electronic structures of polyethylene and polytetrafluoroethylene. PMID- 9992275 TI - Binding energies of biexcitons in AlxGa1-xAs/GaAs multiple quantum wells. PMID- 9992277 TI - Thermochemistry of the gadolinium-copper interface. PMID- 9992276 TI - Photoemission of Xe on Cr(110): Evidence for exponential dependence of the band dispersion on the interatomic spacing. PMID- 9992279 TI - Inequality linking vacancy-formation energy and rigidity in a liquid at melting point from a density-independent pair potential theory. PMID- 9992278 TI - Electron bound states in the vicinity of two orthogonal surfaces. PMID- 9992280 TI - Computer simulation for the roughness and fractal properties of film surfaces. PMID- 9992282 TI - micro Omega -resistance tunnel junctions investigated by weak localization. PMID- 9992281 TI - Residence time and density distribution of silver ions in alpha -Ag2Te by molecular-dynamics simulation. PMID- 9992284 TI - Airy-coordinate Green's-function technique for high-field transport in semiconductors. PMID- 9992285 TI - Excitation energies of the fractional quantized Hall effect in high-mobility AlxGa1-xAs/GaAs heterostructures. PMID- 9992283 TI - Exact perturbative solution of the Wolff model with electron-hole symmetry. PMID- 9992287 TI - Gap mode of Mn in HgTe. PMID- 9992286 TI - Quantum conduction in narrow constrictions. PMID- 9992288 TI - Activationless hopping of correlated electrons in n-type GaAs. PMID- 9992289 TI - Molecular-dynamics study of anharmonic effects in silicon. PMID- 9992290 TI - Lightly doped and compensated quantum wells: The density of states in the dipole model. PMID- 9992291 TI - Negative pressures, clusters, and stiffness thresholds in noncrystalline network solids. PMID- 9992292 TI - Erratum: Accurate and simple density functional for the electronic exchange energy: Generalized gradient approximation PMID- 9992294 TI - Enhancement of cold fusion in metal "hydrides" by screening of proton and deuteron charges. PMID- 9992293 TI - Effect of the electron mean free path in small particles on the extended. PMID- 9992295 TI - Chemical potential oscillations near a barrier in the presence of transport. PMID- 9992297 TI - Analytic approach to charge transfer during atom-surface scattering. PMID- 9992296 TI - Electronic structure near (210) tilt boundaries in nickel. PMID- 9992298 TI - Second-harmonic generation from alkali-metal overlayers. PMID- 9992299 TI - Resonant enhancement of inverse photoemission transitions in bulk niobium. PMID- 9992300 TI - Electronic conductance of an orifice in a magnetic field. PMID- 9992301 TI - Possible mechanism for plasma instabilities in solid-state devices. PMID- 9992302 TI - Stretched-exponential law for carrier capture kinetics of a trapping center in compensated amorphous silicon. PMID- 9992303 TI - Doping-induced structural phase transition in polyacetylene. PMID- 9992304 TI - Self-consistent electronic response and collective excitations of a multiwire superlattice of finite barrier height. PMID- 9992305 TI - Symmetry of the Si shallow donor state in AlAs/GaAs and AlxGa1-xAs/GaAs heterostructures. PMID- 9992307 TI - Carrier-carrier scattering in GaAs: Quantitative measurements from hot (e,A0) luminescence. PMID- 9992306 TI - Tunneling spectroscopy of GaAs/AlxGa1-xAs/GaAs single-barrier heterojunction diodes. PMID- 9992308 TI - Nonanalytic behavior in the band theory of semiconductors. PMID- 9992309 TI - Magnetoconductivity of a two-dimensional electron gas in Al0.3Ga0.7As/Ga1 xINxAs/GaAs pseudomorphic heterostructures in the quantum Hall regime. PMID- 9992310 TI - Elastic screening of surface vibrations: Surface phonons on As:Si(111)(1 x 1). PMID- 9992312 TI - Quenching phenomenon of hopping conduction in neutron-transmutation-doped semi insulating GaAs. PMID- 9992311 TI - Degenerate doping and conduction-band properties of Si studied by synchrotron photoemission of Sb/Si(001). PMID- 9992313 TI - Electron states of a wide quantum well in a tilted magnetic field. PMID- 9992315 TI - Reversible temperature-dependent Fermi-level movement for metal-GaAs(110) interfaces. PMID- 9992314 TI - Surface roughness and correlation length determined from x-ray-diffraction line shape analysis on germanium (111). PMID- 9992316 TI - Fractional quantum Hall effect with spin reversal. PMID- 9992317 TI - Tunable Aharonov-Bohm effect in an electron interferometer. PMID- 9992318 TI - Helium scattering studies of the dynamics of a xenon-monolayer-covered graphite single-crystal surface. PMID- 9992319 TI - Ab initio study of H chemisorption on Li clusters in fcc(100) symmetry. PMID- 9992320 TI - Weak localization in pregraphitic carbon fibers. PMID- 9992321 TI - Surface phonons on the Pt(111) surface: A comparison of He-scattering experiments with lattice-dynamical calculations. PMID- 9992322 TI - Hydrogen as a local probe: Diffusion and short-range order in Ti1-yVy alloys. PMID- 9992323 TI - Surface and thin-film photoemission spectrum of nickel metal: A many-body solution to a two-dimensionally periodic cluster. PMID- 9992324 TI - Corrections to the continuum approximation for the free and bound polarons: The first-relaxed-excited-state energy. PMID- 9992325 TI - Disorder and density-of-states effects on the Hall constant in amorphous transition-metal alloys. PMID- 9992326 TI - Electronic properties of stoichiometric Ba and O overlayers adsorbed on W(001). PMID- 9992327 TI - Generalization of the Lindhard dielectric function to include fluctuation effects. PMID- 9992328 TI - Surface acoustic waves in a simple quasiperiodic system. PMID- 9992329 TI - High-precision sampling for Brillouin-zone integration in metals. PMID- 9992331 TI - Effect of an electric field on a split Bloch band. PMID- 9992330 TI - Existence of Stark-Wannier resonances for nonperiodic one-dimensional systems. PMID- 9992332 TI - First-principles method for calculating electronic properties of layered structures. PMID- 9992334 TI - Plasmons in disordered, two-component, quasi-two-dimensional electron systems. PMID- 9992333 TI - Quasiparticle energies in small metal clusters. PMID- 9992336 TI - Disordered electronic systems: Concentration dependence of the dc conductivity in amorphous transition-metal-metalloid alloys (metallic regime). PMID- 9992335 TI - Extended norm-conserving pseudopotentials. PMID- 9992337 TI - Band-structure-dependent collective states in simple metals. PMID- 9992338 TI - Extensions of Kohn's theorem. PMID- 9992339 TI - Lattice-dynamical calculation of the Kapitza resistance between fcc lattices. PMID- 9992340 TI - Real-space multiple-scattering theory and the electronic structure of systems with full or reduced symmetry. PMID- 9992341 TI - Disruption, atom distributions, and energy levels for Ge/GaAs(110), Ge/InP(110), and Ge/InSb(110) heterojunctions. PMID- 9992342 TI - Raman spectroscopy of two novel semiconductors and related superlattices: Cubic Cd1-xMnxSe and Cd1-xZnxSe. PMID- 9992343 TI - Lifetime for resonant tunneling in a transverse magnetic field. PMID- 9992344 TI - Broadened conductivity tensor and density of states for a superlattice potential in one, two, and three dimensions. PMID- 9992346 TI - Effect of inelastic scattering on impurity resistivity. PMID- 9992345 TI - Hole-capture properties of the electron-irradiation-induced deep-level H5 in p type InP: A charge-controlled bistable model. PMID- 9992347 TI - Mean-field theory for interchain orientational ordering of conjugated polymers. PMID- 9992348 TI - Optical Stark effect of the exciton: Biexcitonic origin of the shift. PMID- 9992349 TI - Effect of virtual screening on the absorption spectrum of a coherently pumped semiconductor. PMID- 9992350 TI - Angle-resolved-photoemission study of AlSb(100) single crystals: Valence-band structure and surface states. PMID- 9992351 TI - Natural and actual valence-band discontinuities in the a-Si/a-Si1-xCx:H system: A photoemission study. PMID- 9992352 TI - Radiofrequency-plasma-deposited hydrogenated fluorinated silicon-carbon alloy films. PMID- 9992354 TI - Electronic mechanism for alkali-metal-promoted oxidation of semiconductors. PMID- 9992353 TI - Optical properties of gallium selenide under high pressure. PMID- 9992355 TI - Nonresonant excitonic optical nonlinearity in semiconductors. PMID- 9992357 TI - Differentiation of electron-paramagnetic-resonance signals of arsenic antisite defects in GaAs. PMID- 9992356 TI - Negative energy gap in HgTe-CdTe heterostructures with thick wells. PMID- 9992358 TI - Polaron Zeeman effect in GaAs/AlxGa1-xAs multiple-quantum-well structures. PMID- 9992359 TI - Energetics and structure of Peierls-Hubbard chains in ground and excited states. PMID- 9992361 TI - Structural stability and valence charge density in a (GaAs)1/(InAs)1 PMID- 9992360 TI - Electronic structure of the (GaP)1/(InP)1 (111) strained-layer superlattice. PMID- 9992362 TI - Adatoms on Si(111) and Ge(111) surfaces. PMID- 9992364 TI - High-current effects in magnetotransport of two-dimensional electrons in GaAs/AlxGa1-xAs heterostructures. PMID- 9992363 TI - Density of states and temperature dependence of the exponent in the light intensity behavior of a-Si:H photoconductivity. PMID- 9992365 TI - Photoacoustic investigation of semiconductors: Influence of carrier diffusion and recombination in PbTe and Si. PMID- 9992366 TI - Optical absorption in metallic-dielectric microstructures. PMID- 9992367 TI - Pattern formation during laser melting of silicon. PMID- 9992369 TI - Structure of the K/Si(100)-(2 x 1) surface: Semiempirical self-consistent-field crystal orbital analysis. PMID- 9992368 TI - Interface states in CdTe-ZnTe strained superlattices. PMID- 9992370 TI - Electron energy levels for a dense electron gas in parabolic GaAs/AlxGa1-xAs quantum wells. PMID- 9992372 TI - Ab initio multicenter tight-binding model for molecular-dynamics simulations and other applications in covalent systems. PMID- 9992371 TI - First-principles pseudopotential and full-potential linear muffin-tin-orbital calculation of anharmonic effects on the lattice-dynamical properties of AlP. PMID- 9992373 TI - Tunneling and relaxation of photogenerated carriers in semiconductor quantum wells. PMID- 9992374 TI - Electron-hole liquid in germanium under high <111> stress. PMID- 9992375 TI - High pressure and DX centers in heavily doped bulk GaAs. PMID- 9992376 TI - Metal/GaP(110) interface formation: Ti, Pd, Ag, and Au adatom deposition. PMID- 9992377 TI - One-phonon resonant Raman scattering: Frohlich exciton-phonon interaction. PMID- 9992378 TI - Oxygen-vacancy complex in silicon. I. 29Si electron-nuclear double resonance. PMID- 9992380 TI - Epitaxial effects on coherent phase diagrams of alloys. PMID- 9992379 TI - Oxygen-vacancy complex in silicon. II. 17O electron-nuclear double resonance. PMID- 9992382 TI - Two-band density-matrix approach to nonlinear optics of excitons. PMID- 9992381 TI - Polaron cyclotron-resonance mass in a single GaAs quantum well. PMID- 9992383 TI - Calculation of dielectric susceptibility for complex ionic systems: Application to a predicted superlattice. PMID- 9992384 TI - Electronic excitation in impact scattering of low-energy He+ from solid surfaces. PMID- 9992386 TI - Anomalously small 4f-5d oscillator strengths and 4f-4f electronic Raman scattering cross sections for Ce3+ in crystals of LuPO4. PMID- 9992385 TI - Intensities of electronic Raman scattering between crystal-field levels of Ce3+ in LuPO4: Nonresonant and near-resonant excitation. PMID- 9992387 TI - Brillouin scattering from corrugated Ag films: Surface-plasmon-mediated enhancement and relaxed wave-vector conservation. PMID- 9992389 TI - Renormalization of hopping integrals due to Coulomb interactions for the Anderson model. PMID- 9992388 TI - Topologies and relative energies of stacking faults occurring in the close-packed phases of Li. PMID- 9992390 TI - One-dimensional model of a liquid metal in the effective-medium approximation in the random limit. PMID- 9992391 TI - Dependence of the elastic characteristics of charge-density-wave conductors on the dc electric field. PMID- 9992392 TI - Interaction between 111In atoms and impurity atoms of s-p elements dissolved in silver. PMID- 9992393 TI - Carbon K-shell near-edge structure: Multiple scattering and band-theory calculations. PMID- 9992394 TI - Reduction of the electron density in GaAs-AlxGa1-xAs single heterojunctions by continuous photoexcitation. PMID- 9992395 TI - Electroabsorption in In0.53Ga0.47As/In0.52Al0.48As asymmetric coupled quantum wells grown on InP substrates. PMID- 9992397 TI - Ma-Brueckner correlation energy. PMID- 9992396 TI - Picosecond photoinduced exciton bleaching in emeraldine base: Crossover in decay mechanisms. PMID- 9992398 TI - Comment on "Critical behavior of the zero-temperature conductivity in compensated silicon, Si:(P,B)" PMID- 9992399 TI - Reply to "Comment on 'Critical behavior of the zero-temperature conductivity in compensated silicon, Si:(P,B)' " PMID- 9992400 TI - Comment on "Silent soft mode in hexagonal barium titanate observed by hyper-Raman scattering" PMID- 9992401 TI - Comment on "Mechanism of nuclear spin-lattice relaxation in insulators at very low temperatures" PMID- 9992402 TI - Reply to "Comment on 'Mechanism of nuclear spin-lattice relaxation in insulators at very low temperatures' " PMID- 9992403 TI - Charge-density-wave transport in hydrogen-doped NbSe3. PMID- 9992404 TI - Mechanism of photoelectron yield enhancement from Ag clusters. PMID- 9992405 TI - Diffusion in random chains: Perturbative expansion around the effective-medium approximation. PMID- 9992406 TI - X-ray standing-wave analysis with high reflection order and near-normal incidence. PMID- 9992407 TI - Density dependence of intersubband transitions in a modulation-doped quantum well. PMID- 9992408 TI - Self-trapped holes in amorphous silicon dioxide. PMID- 9992410 TI - Paramagnetic neutron scattering from Pd2MnSn. PMID- 9992411 TI - Measurement of the occupation lengths of channeled 17-MeV electrons and 54-MeV electrons and positrons in silicon by means of channeling radiation. PMID- 9992409 TI - Zeeman-switched optical-free-induction decay and dephasing in YLiF4:Er3+ PMID- 9992412 TI - Spectroscopy of disordered low-field sites in Cr3+: Mullite glass ceramic. PMID- 9992413 TI - Layer-by-layer growth of solid argon films on graphite as studied by neutron diffraction. PMID- 9992414 TI - Perturbed angular correlation study of impurity interactions in a cubic host metal: Hf in Nb. PMID- 9992415 TI - Electron paramagnetic resonance of a molecular defect in gamma -irradiated IrO2 single crystals. PMID- 9992416 TI - Dechanneling of protons in diamond. PMID- 9992417 TI - Electromagnetic response of layered superconductors. PMID- 9992418 TI - Behavior of the thermal conductivity of dilute 3He-4He mixtures in the superfluid phase. PMID- 9992419 TI - Fermi-liquid theory near the Mott transition. PMID- 9992421 TI - Superconductivity and antiferromagnetism in heavy-electron systems. PMID- 9992420 TI - Superconducting transition temperatures of two-dimensional ultrathin V films and quasi-two-dimensional V-Si multilayered systems. PMID- 9992422 TI - Electron-phonon interactions in the superconducting Chevrel phase compounds Mo6Se8-xSx. PMID- 9992423 TI - Two-body density matrix of a Bose fluid. PMID- 9992424 TI - Magnetic phases in Ising square lattices with mixed bonds. PMID- 9992426 TI - Commensurate states in quasicrystalline superconducting networks. PMID- 9992425 TI - Information-theoretical approach to Josephson tunneling. PMID- 9992427 TI - New method of solving the optimized paired-phonon analysis equations and stability of thin films of liquid 4He at T=0 K. PMID- 9992428 TI - Pairing mechanism in Bi-O superconductors: A finite-size chain calculation. PMID- 9992429 TI - Infrared reflectivity spectra of single crystals of La2CuO4. PMID- 9992431 TI - Some properties of high-Tc superconductors. PMID- 9992430 TI - Power laws in the resistive state in high-Tc superconductors. PMID- 9992433 TI - Validity of the strong-coupling expansion of the two-dimensional Hubbard model. PMID- 9992432 TI - Phenomenological theory for copper oxide high-Tc superconductors. PMID- 9992434 TI - Microwave absorption at low magnetic field in sintered YBa2Cu3O7: Freezing effects at low temperature and superconducting-glass model. PMID- 9992435 TI - Electronic structure, photoemission, inverse photoemission, and x-ray emission spectra of superconducting Ba1-xKxBiO3. PMID- 9992437 TI - Structural and magnetization density studies of La2NiO4. PMID- 9992436 TI - Magnetic ordering and superconductivity in Y1-xPrxBa2Cu3O7-y. PMID- 9992438 TI - Neutron-diffraction study of ErBa2Cu3Ox in the composition range 6.1 <= x <= 7.0. PMID- 9992440 TI - Superconductivity of the Kronig-Penney model. PMID- 9992439 TI - Quasiparticle density of states in the perpendicular direction to the Cu-O planes in YBa2Cu3O7-x single-crystal thin films. PMID- 9992441 TI - Growth, structural, and physical properties of superconducting Nd2-xCexCuO4 crystals. PMID- 9992442 TI - Neutron scattering study of magnetic excitations in YBa2Cu3O6+x. PMID- 9992444 TI - Exact results for randomly decorated magnetic frustrated models of planar CuO2 systems. PMID- 9992443 TI - Upper critical field and normal-state properties of single-phase Y1-xPrxBa2Cu3O7- gamma compounds. PMID- 9992445 TI - Photoemission and inverse-photoemission studies of Ba1-xKxBiO3-y. PMID- 9992447 TI - Oxygen diffusion in the superconducting oxide YBa2Cu3O7-x. PMID- 9992446 TI - Systematic study of (La1-xGdx)1.85Sr0.15CuO4 (0 <= x <= 1): Structure, superconductivity, resistivity, and magnetic properties. PMID- 9992448 TI - Spin dynamics in the two-dimensional quantum antiferromagnet La2CuO4. PMID- 9992449 TI - Vortex phases and dissipation in high-temperature superconducting oxides. PMID- 9992450 TI - Field-dependent specific heat of polycrystalline YBa2Cu3O7-x. PMID- 9992451 TI - Neutron scattering study of the magnetic excitations in metallic and superconducting La2-xSrxCuO4-y. PMID- 9992452 TI - Effective one-band Hamiltonian for the copper-oxygen plane in the superconducting copper oxides. PMID- 9992454 TI - Strong mode locking in systems far from chaos. PMID- 9992453 TI - Micromagnetics and the phenomenological theory of ferromagnets. PMID- 9992456 TI - Spectrum of the biquadratic spin-1 antiferromagnetic chain. PMID- 9992455 TI - Nature of ordering in Potts spin glasses. PMID- 9992457 TI - Spin-correlation functions of the anisotropic XY chain. PMID- 9992459 TI - Distribution and localization of the harmonic magnon modes in a one-dimensional Heisenberg spin glass. PMID- 9992458 TI - Magnetic behavior of compositionally modulated Ni-Cu thin films. PMID- 9992461 TI - Observation of bond-orientational order in the incommensurate fluid phase of potassium chemisorbed on nickel (111). PMID- 9992460 TI - Model for dielectric breakdown in metal-insulator composites. PMID- 9992462 TI - Crossover from nonclassical to Ornstein-Zernike behavior for the order-parameter correlation function. PMID- 9992463 TI - Dissipative quantum dynamics in a boson bath. PMID- 9992464 TI - Ionic conductivity and the phase transitions in Na2SO4. PMID- 9992465 TI - Tensile fracture of heterogeneous solids with distributed breaking strengths. PMID- 9992466 TI - Critical scattering function in a binary fluid mixture: A study of sodium deuteroammonia solution at the critical concentration by small-angle neutron scattering. PMID- 9992467 TI - Preroughening transitions in crystal surfaces and valence-bond phases in quantum spin chains. PMID- 9992469 TI - Anomalous incommensurability and local ordered states at first-order phase transitions. PMID- 9992468 TI - Magnetic behavior of Ce(Cu1-xAgx)6. PMID- 9992470 TI - Phenomenological model of melting in Lennard-Jones clusters. PMID- 9992471 TI - Structure of noise generated on diffusion fronts. PMID- 9992473 TI - Classical magnetic resonance equation for ordered-state systems. PMID- 9992472 TI - Spin-wave theory of the quantum antiferromagnet with unbroken sublattice symmetry. PMID- 9992474 TI - Quantum Monte Carlo study of the two-impurity Kondo Hamiltonian. PMID- 9992475 TI - Synchrotron x-ray study of the structures and phase transitions of monolayer xenon on single-crystal graphite. PMID- 9992476 TI - Soliton theory for realistic magnetic domain-wall dynamics. PMID- 9992477 TI - Theory of antiferromagnetic superlattices at finite temperatures. PMID- 9992478 TI - Dilute spin glass at zero temperature in general dimension. PMID- 9992479 TI - Dynamical Monte Carlo study of crystal growth in a solid-on-solid model. PMID- 9992480 TI - Anomalous diffusion in a lattice-gas wind-tree model. PMID- 9992481 TI - Weak random bonds in the Heisenberg ferromagnet near two dimensions. PMID- 9992482 TI - Low-temperature behavior of the correlation length and the susceptibility of a quantum Heisenberg ferromagnet in two dimensions. PMID- 9992483 TI - Exact duality-decimation transformations and real-space renormalization for the Ising model on a square lattice. PMID- 9992484 TI - Molecular-dynamics studies of the mixed cyanides: I. Structural transformations. PMID- 9992485 TI - From moduli scaling to breakdown scaling: A moment-spectrum analysis. PMID- 9992486 TI - Critical behavior of epitaxial antiferromagnetic insulators: Interdigital capacitance measurement of magnetic specific heat of FeF2 thin films. PMID- 9992487 TI - Paired-magnon analysis of quantum antiferromagnets. PMID- 9992488 TI - Stability of ferrons in antiferromagnets: The role of zero-point fluctuations. PMID- 9992489 TI - Fluid, hexatic, and crystal phases in terephthal-bis-(4n)-alkylanilines. PMID- 9992490 TI - One-dimensional quantum transport in the presence of traps. PMID- 9992491 TI - Melting in multilayer adsorbed films. PMID- 9992492 TI - Dynamic critical behavior of random spin chains in a field. PMID- 9992493 TI - Far-infrared studies of the phase transitions in beta -quinol-methanol and methanol-D4 clathrates. PMID- 9992494 TI - Landau theory of the magnetically ordered phases in CsCoCl3 and related compounds. PMID- 9992496 TI - Monte Carlo simulation of a disordered classical Heisenberg system in one dimension and with long-range ferromagnetic interactions. PMID- 9992495 TI - Surface-enhanced magnetization for uniaxial ferromagnets. PMID- 9992497 TI - Force distribution, multiscaling, and fluctuations in disordered elastic media. PMID- 9992498 TI - Effects of finite size on phase transitions observed in the random-site binary magnetic Ising model. PMID- 9992499 TI - Short-range order in Ising-like models with many-body interactions: Description via effective pair interactions. PMID- 9992500 TI - Sublattice-symmetric spin-wave theory for the Heisenberg antiferromagnet. PMID- 9992501 TI - Monte Carlo study of the Potts model on the square and the simple cubic lattices. PMID- 9992503 TI - Bosonic mean-field theory of quantum Heisenberg spin systems: Bose condensation and magnetic order. PMID- 9992502 TI - Finite-temperature ferromagnetism of nickel. PMID- 9992504 TI - Spin dynamics of EuS in the paramagnetic phase. PMID- 9992505 TI - Phase and amplitude modes of the n=4 incommensurate phase II of biphenyl: Neutron scattering experiments and theoretical results. PMID- 9992506 TI - Vortex-loop scaling in the three-dimensional XY ferromagnet. PMID- 9992507 TI - Kinetics of domain growth, theory, and Monte Carlo simulations: A two-dimensional martensitic phase transition model system. PMID- 9992508 TI - Model for a decorated twin boundary in ferroelastic martensites. PMID- 9992510 TI - Results for the phase diagram of the two-dimensional Coulomb gas. PMID- 9992509 TI - Thermodynamics of Ising models with layered randomness: Exact solutions on square and triangular lattices. PMID- 9992511 TI - Finite-size effects in continuum percolation. PMID- 9992512 TI - Scaling theory of polydispersity, an infinite chain, and the Flory-Huggins approximation. PMID- 9992513 TI - Gradient free energy and intrinsic angular momentum in unconventional superconductors. PMID- 9992515 TI - Temperature, frequency, and rf field dependence of the surface resistance of polycrystalline YBa2Cu3O7-x. PMID- 9992514 TI - Glass behavior of superconducting arrays: Novel finite-size effects. PMID- 9992516 TI - Nearest-neighbor repulsion in electron-doped high-temperature cuprate superconductors. PMID- 9992517 TI - Torque in the irreversible regime on oriented YBa2Cu3O7 crystals. PMID- 9992518 TI - Far-infrared transmission of Bi2Sr2CaCu2O8 films. PMID- 9992519 TI - Magnetic relaxation and critical current density limited by flux creep in Bi1.6Pb0.4Sr1.6Ca2Cu2.8Ox (Tc=115 K) and YBa2Cu3O7-x (Tc=92 K). PMID- 9992521 TI - Pressure dependence of the Cu magnetic order in RBa2Cu3O6+x. PMID- 9992520 TI - Energy dispersions of single-crystalline Bi2.0Sr1.8Ca0.8La0.3Cu2.1O8+ delta superconductors determined using angle-resolved photoelectron spectroscopy. PMID- 9992522 TI - Magnetoresistance of c-axis-oriented epitaxial YBa2Cu3O7-x films above Tc. PMID- 9992524 TI - Chemical state of Tl in the superconductor Tl2Ba2Ca2Cu3O10 studied by x-ray photoelectron spectroscopy. PMID- 9992523 TI - Statistical properties of the spin liquid: Interpretation of the hole states and exchange-mediated pairing. PMID- 9992525 TI - Nonuniversal and surface critical behavior near a defect plane. PMID- 9992526 TI - Antiferromagnetic resonance in La2CuO4+y. PMID- 9992527 TI - Low-temperature behavior of the correlation length and the susceptibility of the ferromagnetic quantum Heisenberg chain. PMID- 9992528 TI - Magnetic interactions in amorphous spin-glass-superconducting multilayers. PMID- 9992530 TI - Spin-Peierls ground states of the quantum dimer model: A finite-size study. PMID- 9992529 TI - Memory functions for the one-dimensional Ising model in a transverse field. PMID- 9992532 TI - Phase diagram of the frustrated XY model on a triangular lattice. PMID- 9992531 TI - Specific-heat anomaly of a ferromagnet in finite magnetic fields. PMID- 9992533 TI - Thermal conductivity of solid N2-Ar alloys. PMID- 9992534 TI - Erratum: Polarization dependence of magnetic x-ray scattering PMID- 9992535 TI - Gauge invariance and flux quantization in the system of fractional-statistics particles. PMID- 9992536 TI - Scanning-tunneling-microscopy-active empty states on the (benzene + CO)/Rh(111) surface investigated by inverse photoemission. PMID- 9992537 TI - Existence of a phase transition in Finkelshtein's model for a disordered Fermi liquid. PMID- 9992539 TI - Hydrogen-mediated model for defect metastability in hydrogenated amorphous silicon. PMID- 9992538 TI - Quantum description of dissipation in normal metals and short constrictions. PMID- 9992540 TI - Uniaxial anisotropic flux trapping in Y-Ba-Cu-O and Bi-Sr-Ca-Cu-O single crystals. PMID- 9992541 TI - Pair-breaking description of the vortex-depinning critical field in YBa2Cu3O7 thin films. PMID- 9992542 TI - Ultrasonic studies of the relation between two-level-tunneling systems, oxygen content, and superconducting transition temperature in YBa2Cu3O7- delta. PMID- 9992543 TI - Bulk superconductivity above 30 K in T-phase compounds. PMID- 9992544 TI - Flux pinning by precipitates in the Bi-Sr-Ca-Cu-O system. PMID- 9992546 TI - Angular dependence of the upper critical field of YBa2Cu3O7- delta single crystals. PMID- 9992545 TI - Valence-band states in Bi2(Ca,Sr,La)3Cu2O8. PMID- 9992547 TI - Stability of superconducting phases in Bi-Sr-Ca-Cu-O and the role of Pb doping. PMID- 9992549 TI - Thermopower studies and resistive anomalies in Ce3In and Ce3In0.9M0.1 alloys (M=Al, Ga, Sn, Ge). PMID- 9992548 TI - Itinerant magnetism in CeRh3B2. PMID- 9992551 TI - Strange attractors in parallel-pumped spin-wave instabilities: Bifurcation of multifractals. PMID- 9992550 TI - Maximum-entropy approaches to quantum electronic transport. PMID- 9992552 TI - Absence of long-range order in three-dimensional Heisenberg models. PMID- 9992553 TI - Ferromagnetism in the one-band Hubbard model. PMID- 9992554 TI - Dielectric measurements of the proton-glass state in Rb0.65(NH4)0.35H2AsO4. PMID- 9992555 TI - Theoretical construction of the magnetic Hamiltonian and zero-temperature anisotropic energy in Nd2Fe14B. PMID- 9992556 TI - Magnetic ordering in La2Cu1-xZnxO4-y. PMID- 9992557 TI - Magnetic order of Pr in PrBa2Cu3O7. PMID- 9992558 TI - Optical excitations from a flux phase. PMID- 9992559 TI - Charge transfer in intermetallics: HfPt3. PMID- 9992560 TI - Numerical study of symmetry effects on localization in two dimensions. PMID- 9992561 TI - Photoelectron diffraction determination of the geometry of a clean metal surface: Ta(100). PMID- 9992563 TI - Nonlocal corrections to Fresnel optics: Comparison of exact solutions with d parameter approximations. PMID- 9992562 TI - Chainlike hydrogen ordering in alpha -ScDx systems. PMID- 9992564 TI - Covalent bonding of sulfur on Ni(001): S as a prototypical adsorbate catalytic poisoner. PMID- 9992565 TI - Simple theory for the atomic-force microscope with a comparison of theoretical and experimental images of graphite. PMID- 9992566 TI - Band structure for dissimilar electromagnetic waves in a periodic structure. PMID- 9992568 TI - Striped-type superstructure in gamma -brass alloys. PMID- 9992567 TI - Temperature dependence of the charge-density-wave mass and relaxation time. PMID- 9992569 TI - Larmor-clock transmission times for resonant double barriers. PMID- 9992570 TI - Second-harmonic generation at simple metal surfaces. PMID- 9992571 TI - Electron-phonon relaxation in pure metals and superconductors at very low temperatures. PMID- 9992573 TI - Simultaneous solution of diagonalization and self-consistency problems for transition-metal systems. PMID- 9992572 TI - Surface plasma resonances in free metal clusters. PMID- 9992574 TI - Spin susceptibility in a two-dimensional electron gas. PMID- 9992575 TI - Crystallization kinetics in amorphous rare-earth-transition-metal alloys. PMID- 9992576 TI - Impurity pinning of sliding charge-density waves. PMID- 9992577 TI - Theory of optical coherence for Wannier excitons: Application to photon echoes. PMID- 9992578 TI - Thermoelectric power during magnetic-field-induced localization in degenerately doped n-type Ge. PMID- 9992579 TI - Reconstruction of the clean and metal-adsorbed Ge(111) surface. PMID- 9992580 TI - Mechanisms of dopant impurity diffusion in silicon. PMID- 9992582 TI - Valence-subband structures of GaAs/AlxGa1-xAs quantum wires: The effect of split off bands. PMID- 9992581 TI - Line-shape theory of magnetoabsorption in semiconductor superlattices. PMID- 9992583 TI - Exciton binding energy and external-field-induced blue shift in double quantum wells. PMID- 9992585 TI - Fluorescence spectra of the layered semiconductor compound MnPS3. PMID- 9992584 TI - Electronic structure of cadmium-telluride-zinc-telluride strained-layer superlattices under pressure. PMID- 9992586 TI - Phonoionization of A+ states in Si under uniaxial stress: Influence of the valence-band structure. PMID- 9992587 TI - Resonant Raman scattering from ZnTe microcrystals: Evidence for quantum size effects. PMID- 9992588 TI - Investigation of the bulk band structure of IV-VI compound semiconductors: PbSe and PbTe. PMID- 9992590 TI - Electronic structure and dispersion of compensated n-i-p-i superlattices with small period lengths. PMID- 9992589 TI - Direct observation of surface-trapped diffracted waves. PMID- 9992591 TI - Valley-mixing effects in short-period superlattices. PMID- 9992592 TI - Chemical and electronic properties of the Ag/GaSb(110) interface formed at room and low temperature. PMID- 9992593 TI - Delayed switching in a phase-slip model of charge-density-wave transport. PMID- 9992594 TI - Formation process of a bipolaron and light-absorption bands in halogen-bridged mixed-valence metal complexes. PMID- 9992595 TI - Hole ionization of Mn-doped GaAs: Photoluminescence versus space-charge techniques. PMID- 9992596 TI - Binding energies of excited shallow acceptor states in GaAs/Ga1-xAlxAs quantum wells. PMID- 9992598 TI - g shift in thermal donors in silicon. PMID- 9992597 TI - Far-infrared determination of effective mass and valence-band offset in the HgTe/CdTe superlattice. PMID- 9992600 TI - Superoperator theory of high-field transport for an electron-phonon system. PMID- 9992599 TI - Analytic distribution for charge carriers in a semiconductor dominated by equivalent intervalley scattering. PMID- 9992601 TI - Band-edge structure of indium-doped Pb1-xSnxTe across the band-inversion region investigated by the far-infrared magnetoplasma method. PMID- 9992603 TI - Anharmonic elastic and phonon properties of Si. PMID- 9992602 TI - Boron carbide structure by Raman spectroscopy. PMID- 9992605 TI - Surface-phonon polariton on gratings of GaP thin slabs: Far-infrared reflection. PMID- 9992604 TI - Electron states associated with 90 degrees partial dislocations in germanium. PMID- 9992606 TI - Near-band-gap photoluminescence of Si-Ge alloys. PMID- 9992607 TI - Pseudo-atomic-orbital band theory applied to electron-energy-loss near-edge structures. PMID- 9992608 TI - Subnanosecond x-ray diffraction from laser-shocked crystals. PMID- 9992609 TI - Oxygen 1s x-ray-absorption edges of transition-metal oxides. PMID- 9992610 TI - Ruby at high pressure. I. Optical line shifts to 156 GPa. PMID- 9992611 TI - Ruby at high pressure. II. Fluorescence lifetime of the R line to 130 GPa. PMID- 9992613 TI - Dissociation of O2 on Cu(001). PMID- 9992612 TI - Equilibrium structures of neutral interstitial hydrogen in zinc-blende BN and BP. PMID- 9992614 TI - Off-normal-incidence effects in the infrared-reflectivity spectra of aluminum phosphate. PMID- 9992615 TI - Elastic behavior of KxNa1-xCN quadrupolar glasses. PMID- 9992616 TI - Structural phase transitions and polymorphism in mixed crystals M(CN)xX1-x (M=Na, K, Rb; X=Cl, Br, I). PMID- 9992618 TI - Interactions between two identical polymer chains studied with first-principles calculations. PMID- 9992617 TI - Electronic structure of the hydrogen-potassium-graphite ternary intercalation compound C8KHx. PMID- 9992619 TI - Al and Ga contributions to the density of states of AlxGa1-xAs. PMID- 9992620 TI - Electronic specific heat and magnetic susceptibility in bismuth thin films under three-dimensional quantization. PMID- 9992621 TI - Correlation energy of a one-component layered electron gas. PMID- 9992622 TI - Magnetoresistance of amorphous Cu-Ti alloys: The spin-orbit scattering time within weak localization. PMID- 9992623 TI - Cyclotron resonance in two dimensions: Electron-electron interactions and band nonparabolicity. PMID- 9992624 TI - Aluminum bulk-plasmon dispersion and its anisotropy. PMID- 9992626 TI - Effects of impurity location on the impurity bands and their spectral densities in quantum wells. PMID- 9992625 TI - Miniband dispersion and excitonic effects on the optical spectra of GaAs/AlxGa1 xAs superlattices. PMID- 9992628 TI - Noncreation of the EL2 defect in neutron-irradiated GaAs. PMID- 9992627 TI - Charge-state-dependent atomic geometries for isolated metal adatoms on GaAs(110). PMID- 9992629 TI - Percolation phenomena in Sr1-xCex PMID- 9992631 TI - Hydrogen interactions in PdHn (1 <= n <= 4). PMID- 9992630 TI - Erratum: Ab initio calculation of pressure coefficients of band gaps of silicon: Comparison of the local-density approximation and quasiparticle results PMID- 9992632 TI - Broadband-noise spectrum in sliding-charge-density-wave conductors. PMID- 9992633 TI - Steady-state quantum kinetic equation. PMID- 9992634 TI - Fractal aggregation of magnetic particles in Ag-Co thin-film surfaces. PMID- 9992636 TI - Epitaxial growth of body-centered-tetragonal copper. PMID- 9992635 TI - Coherent fcc stacking in epitaxial Co/Cu superlattices. PMID- 9992637 TI - Probing interfacial properties with Bloch electrons: Ag on Cu(111). PMID- 9992638 TI - Vibrational-energy relaxation of the metal-molecule stretch mode: CO on Pt(111). PMID- 9992639 TI - Carrier screening effects in semimetallic InAs single-quantum wells. PMID- 9992641 TI - Collective excitation spectra of one-dimensional electron systems. PMID- 9992640 TI - Atomic-resolution scanning-tunneling-microscopy investigations of alkali-metal graphite intercalation compounds. PMID- 9992642 TI - Filled and empty surface electronic states observed on GaAs(110)1 x 1-K. PMID- 9992644 TI - One-dimensional electron gas in GaAs: Periodic conductance oscillations as a function of density. PMID- 9992643 TI - Modeling of hydrogen diffusion in n- and p-type silicon. PMID- 9992645 TI - Effective correlation energy of a Si dangling bond calculated with the local-spin density approximation. PMID- 9992646 TI - Depolarization shift and subband-Landau-level coupling in AlAs-GaAs heterojunctions. PMID- 9992647 TI - Resonant Compton scattering. PMID- 9992649 TI - Photoinduced absorption in hydrogenated amorphous silicon studied by photothermal deflection spectroscopy. PMID- 9992648 TI - Localized electronic states and resonant Raman scattering from localized and quasiresonant phonons in Si-Ge layers. PMID- 9992651 TI - Thermodynamic properties of fcc transition metals as calculated with the embedded atom method. PMID- 9992650 TI - Electron-paramagnetic-resonance study of the Sn DX center in direct-gap Ga0.69Al0.31As. PMID- 9992652 TI - Valence changes and core-level shifts of Sm adsorbed on Mo(110). PMID- 9992653 TI - Theory of the binding energy of an electron in the field of a linear electric quadrupole. PMID- 9992654 TI - Pressure dependence of the melting temperature of metals. PMID- 9992655 TI - Surface anharmonicity on Cu(110). PMID- 9992656 TI - Effect of impurities on the quantized conductance of narrow channels. PMID- 9992657 TI - Scanning tunneling microscope as a probe of the local transport field in mesoscopic systems. PMID- 9992658 TI - Optical-absorption edge and disorder effects in hydrogenated amorphous diamondlike carbon films. PMID- 9992659 TI - Conduction-electron Zeeman splitting in the noble metals. PMID- 9992660 TI - Temperature dependence of the electrical resistivity of potassium films. PMID- 9992661 TI - Nonlinear magneto-optical Kerr effect on a nickel surface. PMID- 9992662 TI - Backscattering and linear response in a disordered metal. PMID- 9992664 TI - Linear response of polycrystals to coupled fields: Exact relations among the coefficients. PMID- 9992663 TI - Divergence in the balance-equation theory of resistivity. PMID- 9992665 TI - Lattice dynamics of quenched diffuse omega phase in Zr0.8Nb0.2. PMID- 9992666 TI - Point-charge effects on the vibrational frequency of CO chemisorbed on Cu and Pd clusters: A model for CO with ionic coadsorbates. PMID- 9992667 TI - Diffraction of He and Ne and selective adsorption of He on Rh(110). PMID- 9992669 TI - Photoemission from ordered thin films of Cu on Ni(100). PMID- 9992668 TI - Structural properties of liquid alkali-metal-lead alloys: NaPb, KPb, RbPb, and CsPb. PMID- 9992670 TI - Empirical electron-phonon coupling constants and anisotropic electrical resistivity in hcp metals. PMID- 9992672 TI - Detection of Alpher-Rubin attenuation and a search for nuclear acoustic resonance of surface waves in tantalum films. PMID- 9992671 TI - Electronic structure of hydrated Ce4+ ions in solution: An x-ray-absorption study. PMID- 9992673 TI - Density of states in a resonant-tunneling structure. PMID- 9992674 TI - Growth of ultrathin Cu layers on Cu2O/Cu(110) and CuO/Cu(110): Sandwich electronic and epitaxial structures. PMID- 9992675 TI - Random-tiling quasicrystal. PMID- 9992676 TI - Semiempirical modified embedded-atom potentials for silicon and germanium. PMID- 9992677 TI - Type-I-type-II transition in ultra-short-period GaAs/AlAs superlattices. PMID- 9992678 TI - Hierarchical classification of fractional quantum Hall states. PMID- 9992679 TI - Electronic properties of Na overlayers on the GaAs(110) surface. PMID- 9992680 TI - Escape process of resonant-tunneling electrons from a quantum well. PMID- 9992681 TI - Hopping conductivity and ac magnetoresistance of p-type InSb using acoustic measurements. PMID- 9992682 TI - Lattice-mode coupling to the charge-density wave in (TMTSF)2ReO4 (where TMTSF is bis-tetramethyltetraselenafulvalene). PMID- 9992683 TI - Quantum transport for Bloch electrons in inhomogeneous electric fields. PMID- 9992684 TI - Surface segregation of third-column atoms in group III-V arsenide compounds: Ternary alloys and heterostructures. PMID- 9992685 TI - Theory of pulse propagation and wave-mixing processes under intense resonant excitation. PMID- 9992687 TI - Infrared magnetospectroscopy of GaAs at magnetic fields up to 150 T. PMID- 9992686 TI - Electron-optical-phonon interaction in single and double heterostructures. PMID- 9992688 TI - 8000-cm-1 line spectrum in platinum-doped silicon studied by perturbation spectroscopy. PMID- 9992690 TI - Free-carrier absorption from Fibonacci sequences of delta -doped layers in silicon. PMID- 9992689 TI - Determination of the binding energy of excitons to neutral donors located at the center or edge of the well or at the center of the barrier in AlxGa1-xAs/GaAs multiple-quantum-well structures. PMID- 9992691 TI - Chemical trends for deep levels associated with vacancy-impurity complexes in semiconductors. PMID- 9992692 TI - Defect equilibria in undoped a-Si:H. PMID- 9992693 TI - Size of exciton bound to a neutral impurity. PMID- 9992694 TI - Magnetophonon effect in the energy relaxation rate of electrons in a GaAs heterostructure. PMID- 9992695 TI - High-field electron transport in quantum wires studied by solution of the Boltzmann equation. PMID- 9992696 TI - Magnetotunneling spectroscopy in a double-barrier heterostructure: Observation of incoherent resonant-tunneling processes. PMID- 9992697 TI - Structural, electronic, and optical properties of polyacetylene from a total energy local-density molecular-cluster approach. PMID- 9992698 TI - Electronic structure of kink and kink-antikink defects in polyacetylene. PMID- 9992700 TI - Exciton-mediated Raman scattering in multiple quantum wells. PMID- 9992699 TI - Enhancing second-order nonlinear optical properties by controlling the wave function in one-dimensional conjugated molecules. PMID- 9992701 TI - Lattice relaxation of DX-like donors in ZnxCd1-xTe. PMID- 9992702 TI - Self-trapped single-particle excitations in equilibrium and photoconductivity in glassy semiconductors. PMID- 9992703 TI - Formation of N centers in pure NaCl. PMID- 9992704 TI - Anharmonic damping in rare-gas multilayers. PMID- 9992705 TI - Raman scattering determination of structures for SiC polytypes: Quantitative evaluation with a revised model of lattice dynamics. PMID- 9992706 TI - Wave-vector dependence of Raman scattering intensity in folded modes of long period alpha -SiC. PMID- 9992707 TI - Dominating Coulomb-interaction effects in amorphous InxOy films. PMID- 9992708 TI - Atom-atom potentials and rare-gas-graphite interactions. PMID- 9992709 TI - Silicide structural evolution in high-dose cobalt-implanted Si(100) crystals. PMID- 9992710 TI - Medium-range structural order and fractal annealing kinetics of radiolytic atomic hydrogen in high-purity silica. PMID- 9992711 TI - Specific heat of (KBr)1-x(KCN)x from 1 to 25 K. PMID- 9992712 TI - Photoemission and electronic structure of FeOOH: Distinguishing between oxide and oxyhydroxide. PMID- 9992714 TI - Chaotic wave functions and ballistic transport in nonlinear superlattices. PMID- 9992713 TI - Interaction and charge transfer in the iron nitride Fe4N. PMID- 9992715 TI - Embedded-atom study of the spontaneous formation of misfit dislocations. PMID- 9992716 TI - Liquid alkali metals: Equation of state and reduced-pressure, bulk-modulus, sound velocity, and specific-heat functions. PMID- 9992717 TI - Rydberg and multiple-electron excitations in x-ray photoabsorption spectra of N2 adsorbed on Fe(111). PMID- 9992718 TI - Splitting of the states derived from the bulk X minima in GaAs-AlAs superlattices. PMID- 9992719 TI - AlxGa1-xAs band-edge dependence on alloy composition. PMID- 9992720 TI - Effect of band structure on Stark shifts in GaAs quantum wells. PMID- 9992722 TI - Interaction between longitudinal-optical-phonon modes of a rectangular quantum wire and charge carriers of a one-dimensional electron gas. PMID- 9992721 TI - Thermal relaxation of the electric conductivity in amorphous silicon-germanium alloys. PMID- 9992723 TI - Current-voltage discontinuities in high-quality two-dimensional electron systems at low Landau-level filling factors. PMID- 9992724 TI - Comment on "Secondary-electron effects in photon-stimulated desorption" PMID- 9992726 TI - Collision broadening of two-dimensional excitons in a GaAs single quantum well. PMID- 9992725 TI - Comment on some "new" results on the multilayer reconstruction of W(100). PMID- 9992728 TI - Direct probing of type-II band configurations in semiconductor superlattices. PMID- 9992727 TI - Blue shift of the absorption edge induced by electric field in a double quantum well demonstrated by electroreflectance. PMID- 9992730 TI - Magnetoquantum oscillations of the phonon-drag thermoelectric power in heterojunctions. PMID- 9992729 TI - Exciton linewidth narrowing in thin-barrier GaAs/AlxGa1-xAs superlattices. PMID- 9992731 TI - EPR of Cu2+-doped cadmium ammonium sulfate: Pseudo-Jahn-Teller effect. PMID- 9992733 TI - Effect of nonconservative forces on the neutralization of sputtered and other desorbed ions. PMID- 9992732 TI - Saturation-resolved-fluorescence spectroscopy of Cr3+:mullite glass ceramic. PMID- 9992734 TI - Crystallography, spectroscopic analysis, and lasing properties of Nd3+:Y3Sc2Al3O12. PMID- 9992736 TI - Quantum effects in deep inelastic neutron scattering. PMID- 9992735 TI - Laser-induced fluorescence and up-conversion processes in LiYF4: Nd3+ laser crystals. PMID- 9992737 TI - Dipole approximation in electron-energy-loss spectroscopy: K-shell excitations. PMID- 9992738 TI - Mossbauer study of Cu0.5Fe0.5Cr2S4. PMID- 9992739 TI - Optical spectra of manganous ion in magnetic trimethyl ammonium manganous trichloride dihydrate PMID- 9992740 TI - Anisotropic superconductivity in C4KHg. PMID- 9992741 TI - Theoretical calculations of x-ray-absorption spectra of copper in La2CuO4 and related oxide compounds. PMID- 9992742 TI - Density dependence of the single-particle kinetic energy of solid hydrogen. PMID- 9992744 TI - Quantum fluctuations in superconducting arrays. PMID- 9992743 TI - Density dependence of the momentum distribution in normal liquid 4He. PMID- 9992746 TI - Cu K-edge x-ray-absorption near-edge structure and electronic structure of Nd2 xCexCuO4-y and La2-xSrxCuO4. PMID- 9992745 TI - Structure of an isolated vortex in an anisotropic type-II superconductor. PMID- 9992747 TI - Coulomb blockade in a superlattice of normal tunnel junctions. PMID- 9992749 TI - Elastic softening and internal friction in La2-xSrxCuO4. PMID- 9992748 TI - Functional-integral approach to strongly correlated Fermi systems: Quantum fluctuations beyond the Gutzwiller approximation. PMID- 9992750 TI - Critical properties of a dilute gas of vortex rings in three dimensions and the lambda transition in liquid helium. PMID- 9992751 TI - Temperature dependence of elastic constants: A material-independent parameter and data in hcp 4He. PMID- 9992753 TI - Phase locking of long Josephson junctions. PMID- 9992752 TI - Anisotropic exchange and superconductivity in UPt3. PMID- 9992754 TI - Kondo effect and superconductivity in Nd2-xCexCuO4- delta compounds. PMID- 9992757 TI - Theory of electron distributions and 63Cu and 17O nuclear quadrupole interactions in the high-Tc system YBa2Cu3O7. PMID- 9992756 TI - Coupled-cluster approximation for spin lattices: Application to solid 3He. PMID- 9992755 TI - Valence state for bismuth in the superconducting bismuth cuprates. PMID- 9992758 TI - Light scattering from quantum spin fluctuations in R2CuO4 (R=La, Nd, Sm). PMID- 9992760 TI - Compressibility and superfluidity in the fractional-statistics liquid. PMID- 9992759 TI - Magnetoresistance and the spin-flop transition in single-crystal La2CuO4+y. PMID- 9992761 TI - Super-radiant multifluxon dynamics in a system of parallel-coupled Josephson junctions. PMID- 9992762 TI - Ground state of a two-dimensional charged-boson system. PMID- 9992763 TI - Critical-current-free-energy relations in high-Tc superconductors. PMID- 9992764 TI - Antiferromagnetism and superconductivity in a two-dimensional Heisenberg model: Further studies on possible coexistence. PMID- 9992765 TI - First-principles investigation of the superconducting properties of Tl2Ba2CaCu2O8 and the spin instability of Cr using a new approach of configuration-interaction of band-structure wave functions. PMID- 9992766 TI - Anomalous oxygen isotope effect in La2-xSrxCuO4. PMID- 9992767 TI - Cluster-model calculation of the electronic structure of CuO: A model material for the high-Tc superconductors. PMID- 9992768 TI - Anomalous peak in the thermopower of YBa2Cu3O7- delta single crystals: A possible fluctuation effect. PMID- 9992769 TI - Far-infrared sphere resonance in isolated superconducting particles. PMID- 9992771 TI - Doping of charge density wave in Ba1-xKxBiO3. PMID- 9992770 TI - Superconductivity in a two-dimensional Fermi gas: Evolution from Cooper pairing to Bose condensation. PMID- 9992772 TI - Ground-state properties of a single oxygen hole in a CuO2 plane. PMID- 9992773 TI - Evolution and the concomitant disappearance of high-Tc superconductivity with carrier concentration in the La2-xSrxCuO4- delta system (0.0 <= x <= 1.2): Crossover from a Mott insulator to a band metal. PMID- 9992774 TI - Ising-model Monte Carlo simulations: Density of states and mass gap. PMID- 9992776 TI - Field-theoretical approach to critical phenomena. PMID- 9992775 TI - Hierarchical Wentzel-Kramers-Brillouin quantization of nonseparable variables: Magnetic-flux effects in a varying width geometry. PMID- 9992778 TI - Perturbational treatment of correlation effects in the Hubbard model. PMID- 9992777 TI - Enhanced backscattering of electrons in a magnetic field. PMID- 9992780 TI - Antiferromagnetic planar-rotator model with further-neighbor interactions. PMID- 9992779 TI - Stability analysis of an Ising spin glass with transverse field. PMID- 9992781 TI - Surface melting of Ni(110). PMID- 9992782 TI - High-magnetic-field EPR in Cd1-xMnxTe. PMID- 9992783 TI - Effects of high magnetic fields on charge-density waves in NbSe3. PMID- 9992784 TI - Grain-size effects in ferroelectric switching. PMID- 9992785 TI - Surface reflections and optical transport through random media: Coherent backscattering, optical memory effect, frequency, and dynamical correlations. PMID- 9992786 TI - Magnetic exchange interactions in Co-based II-VI diluted magnetic semiconductors: Zn1-xCoxS. PMID- 9992787 TI - Calculation of parameters in model Hamiltonians. PMID- 9992788 TI - Role of frustration interactions in the thermal properties of tiling models for glasses. PMID- 9992789 TI - Spin-wave calculations for multilayered structures. PMID- 9992791 TI - Hidden weak ferromagnetism in slightly doped antiferromagnets. PMID- 9992790 TI - Specific heat in a magnetic field: A probe of the magnetic ground-state properties of heavy-fermion Ce(Ru2-xRhx)Si2-yGey. PMID- 9992792 TI - Magnetic properties of ultrathin fcc Fe(111)/Ru(0001) films. PMID- 9992793 TI - Frohlich conduction in spin-density waves. PMID- 9992794 TI - Percolation model of nuclear magnetic relaxation in porous media. PMID- 9992796 TI - Specific heat of the ytterbium monopnictides above 5 K from a band-structure calculation. PMID- 9992795 TI - Magnetic properties and Fermi surface of antiferromagnetic SmCu6. PMID- 9992797 TI - Oxygen on Ru(001): Critical behavior of a p(2 x 1) order-disorder transition. PMID- 9992799 TI - ESR detection of low-frequency fluctuations and optical-phonon-induced T1 relaxation for KH2PO4:SeO43- PMID- 9992798 TI - Zero-field microSR measurements in CuMn and AuMn spin glasses interpreted in the frame of a fractal cluster model. PMID- 9992800 TI - Collective excitations in a doped antiferromagnet. PMID- 9992801 TI - Super-roughening: A new phase transition on the surfaces of crystals with quenched bulk disorder. PMID- 9992802 TI - Thermal stability and the origin of perpendicular anisotropy in amorphous Tb-Fe Co films. PMID- 9992803 TI - Kinetics of diamagnetic phase transitions. PMID- 9992804 TI - Properties of the chiral-spin-liquid state. PMID- 9992805 TI - Fluctuation effects in first-order phase transitions: Theory and model for martensitic transformations. PMID- 9992806 TI - Scaling theory of interacting light and heavy fermions in one dimension. PMID- 9992807 TI - Nonlinear magnetodynamic waves on magnetic materials. PMID- 9992808 TI - Relaxation study in percolating solids. PMID- 9992809 TI - Critical behavior at the ferromagnetic phase transition of (Fe1-xCrx)85B15 metallic glasses close to the critical concentration of ferromagnetic long-range order. PMID- 9992811 TI - Comparison between frequency-dependent specific heat and dielectric relaxation of glycerol and propylene glycol. PMID- 9992810 TI - Quantum theory of the Faraday magneto-optical effect in paramagnetic media. PMID- 9992812 TI - Elementary excitations of spin-aligned deuterium. PMID- 9992813 TI - Accurate analytic approximation for magnetic-field penetration into superconducting aluminum. PMID- 9992814 TI - Measurement of Teff for Cu in YBa2Cu3O7 by neutron resonance absorption. PMID- 9992815 TI - Intermodulation of the two incommensurate waves in Bi2-xPbxSr2CaCu2Oy superconducting crystals. PMID- 9992816 TI - Measurement by EPR of the penetration depth in the high-Tc superconductors TlBa2Ca2Cu3Ox and Bi2Ca2SrCu2Ox. PMID- 9992817 TI - Test of universality for three-dimensional models of mechanical breakdown in disordered solids. PMID- 9992818 TI - Symmetry-breaking fixed points in the two-dimensional planar model. PMID- 9992819 TI - Effect of anisotropy on spin-wave surface magnetization in a Heisenberg ferromagnet. PMID- 9992821 TI - Cusp catastrophe in the ferromagnetic resonance spectrum of a layered ferromagnet. PMID- 9992820 TI - d-dimensional conductivity, conductivity exponent, and critical concentration in the site problem. PMID- 9992823 TI - Comment on "Optical and electron paramagnetic resonance studies of Fe impurities in yttrium aluminum garnet crystals" PMID- 9992822 TI - Low-temperature spin glass in IV-VI semimagnetic semiconductors. PMID- 9992824 TI - Spin-lattice coupling coefficients and the method of identifying the dominant mechanism for 6S-state splitting. PMID- 9992825 TI - Erratum: "Elastic constants of the polycrystalline Bi-Pb-Sr-Ca-Cu-O superconductor" PMID- 9992826 TI - Solidification instability of quantum fluids. PMID- 9992828 TI - Ion neutralization mediated by a molecular state: He+ on D-covered TiC(111). PMID- 9992827 TI - Sensitivity of positron-annihilation-induced Auger-electron spectroscopy to the top surface layer. PMID- 9992829 TI - Repulsion-induced superconductivity in a multiband Hubbard model. PMID- 9992830 TI - Binding of holes in the Hubbard model. PMID- 9992831 TI - Prediction of decoupling in high-temperature superconductors. PMID- 9992833 TI - Electronic tunneling into an isolated vortex in a clean type-II superconductor. PMID- 9992832 TI - Giant torque magnetization anisotropy in Tl2Ba2CaCu2Ox thin films. PMID- 9992834 TI - Ion-channeling anomalies at the superconducting transition temperature in single crystal YBa2Cu3O7-y. PMID- 9992836 TI - Fluctuation conductivity and normal resistivity in YBa2Cu3Oy. PMID- 9992835 TI - Resonant Raman scattering in the Pb2Sr2(Y,Ca)Cu3O8+ delta superconductor. PMID- 9992837 TI - Short-time relaxation of the critical current in oriented grained YBa2Cu3Ox and granular (Bi,Pb)2 Sr2Ca2Cu3Ox. PMID- 9992838 TI - Quasiparticle tunneling in Bi-Sr-Ca-Cu-O thin films. PMID- 9992840 TI - Quantum percolation in electron cuprate superconductors Nd2-xCexCuO4-y. PMID- 9992839 TI - Normal-state transport properties of Bi2+xSr2-yCuO6+ delta crystals. PMID- 9992841 TI - Superconducting pairing of the extended multiband Hubbard model: A weak-coupling study. PMID- 9992842 TI - Carrier-density-related superconductivity in bismuth cuprates. PMID- 9992843 TI - Possiblity of LiPdHx as a new ionic superconductor. PMID- 9992844 TI - Optical reflectivity spectra of single-crystal Bi2Sr2Can-1CunO2n+4+x (n=1 and 2). PMID- 9992845 TI - Nonlinear magnetization of Y-Ba-Cu-O crystals. PMID- 9992846 TI - BCS versus Josephson pair hopping between the CuO2 layers in high-Tc superconductors. PMID- 9992847 TI - Positron lifetime in a resonating-valence-bond superconductor. PMID- 9992848 TI - Evidence for the heavy-fermion normal state of high-temperature superconductors from the theory of spectroscopy. PMID- 9992849 TI - Interacting-walls approximation in the two-dimensional axial third-nearest neighbor Ising model. PMID- 9992850 TI - Self-consistent theory of Anderson localization for the tight-binding model with site-diagonal disorder. PMID- 9992851 TI - Spectral function of a hole in a Hubbard antiferromagnet. PMID- 9992852 TI - Exponentially small growth probabilities in diffusion-limited aggregation. PMID- 9992853 TI - Energy-level assignments for the 1E and 3T1a states of MgO:Ni2+ PMID- 9992854 TI - Stopping power for low-velocity heavy ions: (0-1.0)-MeV/nucleon Mg ions in 17 (Z=22-79) elemental solids. PMID- 9992855 TI - Time-differential perturbed-angular-correlation study of hyperfine interactions at 111Cd(111In) in alpha -Fe2O3. PMID- 9992856 TI - 11B spin-lattice relaxation and disorder modes in ionic glassy conductors (AgI)x(Ag2O PMID- 9992857 TI - Range and thermal-behavior studies of Au and Bi implanted into photoresist films. PMID- 9992858 TI - Dynamics of silver ions in (AgI)x-(Ag2O-nB2O3)1-x glasses: A 109Ag nuclear magnetic resonance study. PMID- 9992859 TI - Hyperfine-interaction parameters for a Cd probe atom at the Fe/Kr interface. PMID- 9992861 TI - Transport model of thermal and epithermal positrons in solids. I. PMID- 9992860 TI - Magnetic linear birefringence in rare-earth garnets: Crystal-field effects and the Judd-Ofelt approximation. PMID- 9992863 TI - Laser-induced instantaneous spectral diffusion in Tb3+ compounds as observed in photon-echo experiments. PMID- 9992862 TI - Transport model of thermal and epithermal positrons in solids. II. PMID- 9992864 TI - Excited-state dynamics and energy transfer of +4 curium in cerium tetrafluoride. PMID- 9992865 TI - 35Cl spin-spin relaxation time T2 in Rb2ZnCl4 studied by nuclear quadrupole resonance. PMID- 9992866 TI - Positronium hydride in hydrogen-laden thermochemically reduced MgO single crystals. PMID- 9992867 TI - Temperature dependence of positron diffusion in cubic metals. PMID- 9992869 TI - Energy transfer from rare gases to surfaces: Collisions with gold and platinum in the range 1-4000 eV. PMID- 9992868 TI - Cyanide-orientation distribution by single-crystal NMR of K(CN)xBr1-x. PMID- 9992870 TI - Nuclear quadrupole resonance of 35Cl nuclei in glassy solution of chlorobenzene in pyridine. PMID- 9992871 TI - Investigation of delta -electron emission in collisions of highly charged fast Ne projectiles with carbon-foil targets. PMID- 9992872 TI - Multiple small-angle scattering from a bidisperse Markov medium. PMID- 9992873 TI - Differential resistance and critical-current distribution in YBa2Cu3O7-x ceramics. PMID- 9992874 TI - 63Cu Knight shifts in the superconducting state of YBa2Cu3O7- delta (Tc=90 K). PMID- 9992875 TI - Spin excitations and pairing gaps in the superconducting state of YBa2Cu3O7- delta. PMID- 9992876 TI - X-ray absorption of BaBiO3 and superconducting BaBi0.25Pb0.75O3. PMID- 9992878 TI - Charge-transfer polarization wave in the high-Tc oxides and its relevance to superconducting pairing. PMID- 9992877 TI - Phonon density of states of the quasi-one-dimensional molybdenum selenides M2Mo6Se6 (M=Tl, In, Rb, and vacancy): Evidence of Einstein-like M-atom modes in the superconducting compounds. PMID- 9992879 TI - Oxygen dependence of the linear term in the specific heat of YBa2Cu3O7- delta. PMID- 9992880 TI - Solving the Ginzburg-Landau equations by simulated annealing. PMID- 9992881 TI - Influence of electronic polarization on the core x-ray photoemission spectra of Ce compounds. PMID- 9992882 TI - Dissipation in a one-dimensional superconductor: Evidence for macroscopic quantum tunneling. PMID- 9992883 TI - Infrared spectrum of the electron bubble in liquid helium. PMID- 9992884 TI - Suppression of superconductivity in PrBa2Cu3O7: 4f and conduction-band hybridization effect. PMID- 9992885 TI - Scaling function of the specific heat for a high-temperature superconductor in a magnetic field. PMID- 9992886 TI - Charge-density wave with imperfect nesting and superconductivity. PMID- 9992888 TI - Pseudogaps and the spin-bag approach to high-Tc superconductivity. PMID- 9992887 TI - Simulations of the onset of diffusion in a flux-line lattice in a random potential. PMID- 9992889 TI - Lattice dynamics of high-Tc superconductors: Optical modes of the thallium-based compounds. PMID- 9992890 TI - Physical properties of Bi2Sr2Can-1CunOy (n=1,2,3). PMID- 9992891 TI - Hole superconductivity and the high-Tc oxides. PMID- 9992892 TI - Dependence of some electromagnetic properties of superconductors on coupling strength. PMID- 9992893 TI - Vortex-persistent current interaction, Meissner effect, and diamagnetic shielding in a ring of YBa2Cu3O7. PMID- 9992894 TI - Effects of nonmagnetic impurity atoms on the spin-density-wave model of high temperature superconductivity. PMID- 9992895 TI - Lattice vibrations in La2CuO4. PMID- 9992896 TI - Scaling relations for two-component charged systems: Application to metallic hydrogen. PMID- 9992897 TI - Compressive-stress-induced Tc increase of the low-Tc Bi1.6Pb0.4Sr2Ca2Cu3Ox phase. PMID- 9992899 TI - Anisotropic magnetic relaxation, hysteresis, and Meissner fraction in untwinned single-crystal YBa2Cu3O7- delta produced without applying stress. PMID- 9992898 TI - Madelung energy and charge transfer in Pb2Sr2Y1-xCaxCu3O8+ delta : Possible extra superconducting regions. PMID- 9992900 TI - Preparation process, crystal structure, and physical properties of the 110-K single-phase Pb-Bi-Sr-Ca-Cu-O superconductor. PMID- 9992901 TI - Magnetic correlations in YBa2Cu3O6+x at superconducting concentrations. PMID- 9992903 TI - Critical-current suppression in microwave-irradiated granular high-Tc films. PMID- 9992902 TI - Electron-phonon coupling in the rare-earth metals. PMID- 9992904 TI - Growth and properties of oxygen- and ion-doped Bi2Sr2CaCu2O8+ delta single crystals. PMID- 9992905 TI - Phenomenological dynamics for two-dimensional superfluids. PMID- 9992906 TI - Cationic substitution and role of oxygen in the n-type superconducting T' system Nd2-yCeyCuOz. PMID- 9992907 TI - Electronic structure of the YBa2Cu3O7 superconductor containing twin boundaries. PMID- 9992908 TI - Microwave dissipation in single-crystal high-Tc superconductors. PMID- 9992909 TI - Thermal conductivity of polycrystalline YBa2Cu3O7- delta in a magnetic field. PMID- 9992910 TI - Origin of heavy-fermion behavior in CeCu2Si2. PMID- 9992911 TI - Bulk superconducting Y2Ba4Cu7O15- delta and YBa2Cu4O8 prepared in oxygen at 1 atm. PMID- 9992912 TI - Dissipative flux motion in high-temperature superconductors. PMID- 9992913 TI - Theory of photoemission and inverse photoemission in the presence of strong correlations: Application to high-Tc materials. PMID- 9992914 TI - Microwave phase locking of Josephson-junction fluxon oscillators. PMID- 9992915 TI - Role of oxygen in PrBa2Cu3O7-y: Effect on structural and physical properties. PMID- 9992916 TI - Long-range Coulomb interactions and the onset of superconductivity in the high-Tc materials. PMID- 9992917 TI - Internal friction and Young's modulus in the Bi(Pb)-Sr-Ca-Cu-O superconductor. PMID- 9992919 TI - Systematics in the oxygen 1s core-level photoemission spectra from metal oxides: Model calculations. PMID- 9992918 TI - Theoretical analysis of the concentration and distribution of carriers in YBa2Cu3O7-x. PMID- 9992921 TI - Theory of Haldane-gap antiferromagnets in applied fields. PMID- 9992920 TI - Anisotropic pressure dependence of the superconducting transition in YBa2Cu3O7- delta single crystals. PMID- 9992923 TI - Critical magnetic field of disordered Zr-Cu alloys: Density of states and spin orbit scattering time. PMID- 9992922 TI - Large-scale flow in competing-interaction systems. PMID- 9992924 TI - Ground state of a mobile vacancy in a quantum antiferromagnet: Small-cluster study. PMID- 9992925 TI - Renormalization-group approach to domain-growth scaling. PMID- 9992926 TI - Specific heat of quantum-spin chains: Application to (C6H11NH3)CuBr3 and (C6H11NH3)CuCl3. PMID- 9992927 TI - Quasielastic response with a real-time path-integral Monte Carlo method. PMID- 9992929 TI - Structural phases of sodium-doped polyparaphenylene vinylene. PMID- 9992928 TI - Integral expansion often reducing to the density-gradient expansion, extended to non-Markov stochastic processes: Consequent non-Markovian stochastic equation whose leading terms coincide with Schrodinger's. PMID- 9992931 TI - Magnetic properties of Heisenberg-type ferromagnetic films with a sandwich structure. PMID- 9992930 TI - X-ray-absorption near-edge structure study in mixed-valent samarium systems. PMID- 9992932 TI - Photoemission study of the ferromagnetic Kondo system CeRh3B2. PMID- 9992934 TI - Double-well potential of SO4 in NH4LiSO4, LiRbSO4, and mixed-crystal LiRb1 xCsxSO4 (x=0.097) studied by x-ray diffraction. PMID- 9992933 TI - Role of domain walls in the ground-state properties of the spin-1/2 XXZ Hamiltonian in the linear chain. PMID- 9992936 TI - Electronic and magnetic structure of the ternary fcc Mn-Fe-Ni system. II. Disordered alloys and ferromagnetic-antiferromagnetic interfaces. PMID- 9992935 TI - Electronic and magnetic structure of the ternary fcc Mn-Fe-Ni system. I. Ordered compounds. PMID- 9992938 TI - Chromium: A possible spin-split metal. PMID- 9992937 TI - Spin-split states in metals. PMID- 9992939 TI - Wetting near grain boundaries and defect planes, and its connection with wetting at walls and free surfaces. PMID- 9992940 TI - Monte Carlo study of two-step defect melting. PMID- 9992941 TI - Growth and dynamical roughening of ideal quasicrystal facets. PMID- 9992943 TI - Low-lying disordered states when ground-state long-range order exists; large amplitude spin waves. PMID- 9992942 TI - Anyons in a magnetic field. PMID- 9992944 TI - Numerical solution of large s=1/2 and s=1 Heisenberg antiferromagnetic spin chains using a truncated basis expansion. PMID- 9992945 TI - Magnetic excitations in monodomain ferromagnetic uranium telluride. PMID- 9992946 TI - Influence of external magnetic field on the reentrant spin-glass state of Au0.832Fe0.168 alloy. PMID- 9992947 TI - Symmetry superposition studied by surface second-harmonic generation. PMID- 9992948 TI - Phase separation in a t-J model. PMID- 9992949 TI - Magnetic properties of icosahedral Al-Cr-Mn-Ge alloys. PMID- 9992950 TI - High-spin and low-spin states in Invar and related alloys. PMID- 9992951 TI - Two-dimensional Coulomb gas studied in the sine-Gordon formulation. PMID- 9992952 TI - Dislocation dynamics. I. A proposed methodology for deformation micromechanics. PMID- 9992953 TI - Dislocation dynamics. II. Applications to the formation of persistent slip bands, planar arrays, and dislocation cells. PMID- 9992954 TI - Electrical resistivity, thermal conductivity, and thermopower in the U= PMID- 9992955 TI - Staggered flux phases in the t-J model. PMID- 9992956 TI - Quantum isoenthalpic-isotension method for studying solid phase transformations. PMID- 9992957 TI - Critical dynamics of the two-dimensional kinetic Ising model: High-temperature series analysis of the autorelaxation time. PMID- 9992958 TI - Dynamics of ordering processes in annealed dilute systems: Island formation, vacancies at domain boundaries, and compactification. PMID- 9992959 TI - Internal structure of hole quasiparticles in antiferromagnets. PMID- 9992960 TI - Stoner exchange interaction in transition metals. PMID- 9992961 TI - 10(6)-particle molecular-dynamics study of homogeneous nucleation of crystals in a supercooled atomic liquid. PMID- 9992962 TI - Sound propagation in charge- and spin-density waves. PMID- 9992963 TI - Exact solutions of two-hole and hole-magnon bound states in a ferromagnet. PMID- 9992965 TI - Quantum Ising models in transverse fields for a class of one-dimensional quasiperiodic lattices. PMID- 9992964 TI - Diffusion of particles in an inhomogeneous medium: High-friction limit. PMID- 9992966 TI - Effects of impurities on the phase transition and critical phenomena of a chemisorbed overlayer. PMID- 9992968 TI - Quasiparticle band structure for the Hubbard systems: Application to alpha CeAl2. PMID- 9992967 TI - First-order magnetic-field-induced phase transition in epitaxial iron films studied by magnetoresistance. PMID- 9992970 TI - One-dimensional generalized Fibonacci tilings. PMID- 9992969 TI - Phase transitions in the one-dimensional Ising model with ferromagnetic and antiferromagnetic interactions. PMID- 9992971 TI - Liquidlike model for thermal conductivity in superionic conductors. PMID- 9992972 TI - Kinks in the Frenkel-Kontorova model with long-range interparticle interactions. PMID- 9992973 TI - Spin-dynamics study of the classical ferromagnetic XY chain. PMID- 9992975 TI - Hopping conductivity in the extended hard-core square lattice gas. PMID- 9992974 TI - Dual site-bond description of heterogeneous surfaces. PMID- 9992976 TI - First-order magnetization process and spin phase diagram of Nd2Fe14-xGa xB and Nd2Fe11.5-xCo2.5GaxB. PMID- 9992977 TI - Heat capacity and torsional oscillator studies of molecular hydrogen in porous Vycor glass. PMID- 9992978 TI - Isotope effect at higher critical temperatures. PMID- 9992979 TI - Understanding hybridization effects in carbon Auger spectra. PMID- 9992981 TI - Raman study of CuO single crystals. PMID- 9992980 TI - Electronic structure of Bi-based copper oxide superconductors: A comparative photoemission study of Bi2Sr2CaCu2O8, Bi2Sr2CuO6, and Bi2Sr2CoO6+ delta. PMID- 9992982 TI - Calculated properties of the commensurate monolayers of helium and hydrogen on graphite. PMID- 9992983 TI - Physical and chemical effects of silver additions to Bi2Sr2CaCu2O8 and (Bi,Pb)2Sr2Ca2Cu3O10. PMID- 9992984 TI - Gap anisotropy in high-Tc superconductors: A unified picture. PMID- 9992985 TI - Resonant-photoemission study of Nd2-xCexCuO4. PMID- 9992986 TI - Validity of the single-band model. PMID- 9992987 TI - Infrared diffuse reflectivity study of high-Tc superconductors. PMID- 9992988 TI - Tunneling study of Bi2Pb0.4Sr2Ca2.5Cu3.5Oy with Tc=105 K. PMID- 9992989 TI - R2Ba4Cu7O15- delta : A 92-K bulk superconductor. PMID- 9992990 TI - Comparison of Monte Carlo and analytic results for nearest-available-neighbor pairing in one, two, and three dimensions. PMID- 9992991 TI - 23Na NMR study of the phase transition in deuterated ammonium Rochelle salt. PMID- 9992992 TI - Soft-mode behavior and the dipolar glass transition in KTa1-xNbxO3. PMID- 9992993 TI - Spectral and magnetic transitions in the quantum Ising model. PMID- 9992994 TI - Question of superoxide in La2CuO4+ delta. PMID- 9992996 TI - Validity of the t-J model. PMID- 9992995 TI - Reply to "Question of superoxide in La2CuO4+ delta " PMID- 9992998 TI - Erratum: "Critical exponents for ferromagnetic systems with Ruderman-Kittel Kasuya-Yosida interactions" PMID- 9992997 TI - Reply to "Validity of the t-J model" PMID- 9992999 TI - Optical anisotropy of Bi2Sr2CaCu2O8. PMID- 9993000 TI - Nuclear hyperfine structure of muonium in CuCl resolved by means of avoided level crossing. PMID- 9993002 TI - 205Tl NMR in Tl2Ba2CuO6 and the t-J model. PMID- 9993001 TI - Triplet-state defect in high-purity silica glass. PMID- 9993003 TI - d-wave Cooper pairing near or in the spin-density-wave state. PMID- 9993005 TI - Initial magnetization curve and weak-link properties in Ag2O-doped LaBa2Cu3O7-y. PMID- 9993004 TI - Dynamical simulations of fractional giant Shapiro steps in two-dimensional Josephson arrays. PMID- 9993006 TI - Carrier reflection at the superconductor-semiconductor boundary observed using a coplanar-point-contact injector. PMID- 9993007 TI - Generalized flux states of the t-J model. PMID- 9993008 TI - Spin-polarization enhancement of dilute 3He-4He solutions through porous media. PMID- 9993009 TI - Unusual low-frequency electromagnetic response in anisotropic superconductors: Application to UPt3. PMID- 9993010 TI - Energy gap, Tc, and density of states in high-temperature superconductors for retarded s- and d-wave interactions. PMID- 9993011 TI - Weak coupling and anisotropy in the magnetic penetration depth of the high temperature superconductor Tl2Ca2Ba2Cu3O10+ delta. PMID- 9993012 TI - Comparative study of fluorescence- and electron-yield detection on YB2Cu3O7- delta at the O K edge through x-ray absorption. PMID- 9993014 TI - Anisotropy in the thermal expansion of heavy-fermion UPt3 at the superconducting transition. PMID- 9993013 TI - Statistics in a dissipative medium. PMID- 9993015 TI - Angular correlations of waves in disordered systems: New numerical results. PMID- 9993017 TI - O(2) symmetry and critical lines of the antiferromagnetic Ising models. PMID- 9993016 TI - Orbital polarization in narrow-band systems: Application to volume collapses in light lanthanides. PMID- 9993019 TI - Diffusion of 3He quasiparticles in dilute 3He-4He solution confined in porous media. PMID- 9993018 TI - Limits d--> PMID- 9993021 TI - Magnetization steps in iron-based diluted magnetic semiconductors. PMID- 9993020 TI - Effect of topological excitations in the two-dimensional quantum Heisenberg antiferromagnet. PMID- 9993022 TI - Antiferromagnetic Heisenberg model on a quasiperiodic lattice with hierarchical interactions. PMID- 9993024 TI - Effects of level quantization on the supercurrent decay in Josephson junctions: The nonstationary case. PMID- 9993023 TI - bcc lead at 109 GPa: Diffraction studies to 208 GPa. PMID- 9993025 TI - Electronic structure of Cu75Au25 disordered alloy. PMID- 9993027 TI - Atomic structure of icosahedral Al6Mg4Cu. PMID- 9993026 TI - Effective dielectric response of polydispersed composites. PMID- 9993028 TI - Nonequilibrium in metallic microstructures in the presence of high current density. PMID- 9993029 TI - Temperature dependence of the electrical conductivity of amorphous VxSi1-x. PMID- 9993030 TI - Dynamics of charge-density waves in electron-irradiated K0.3MoO3. PMID- 9993031 TI - Conductance of a disordered linear chain including inelastic scattering events. PMID- 9993032 TI - Far-infrared absorption by small silver particles in gelatin. PMID- 9993033 TI - Pressure-induced s-->d transfer and the equation of state of molybdenum. PMID- 9993034 TI - Conduction-electron g factor on the X-pocket holes in iridium. PMID- 9993035 TI - Variational mesh for quantum-mechanical simulations. PMID- 9993036 TI - Oxygen on Ni(111): A multiple-scattering analysis of the near-edge x-ray absorption fine structure. PMID- 9993037 TI - Photoemission studies of the low-temperature reaction of metals and oxygen. PMID- 9993039 TI - Surface-controlled deuterium-palladium interactions. PMID- 9993038 TI - Composition, structure, and morphology for Ag deposition on Cu(110): A medium energy ion-scattering study. PMID- 9993040 TI - Phonon properties of a class of one-dimensional quasiperiodic systems. PMID- 9993041 TI - Anharmonic lattice vibrations in noble metals. PMID- 9993042 TI - Anharmonic damping of phonon modes in the fcc metals. PMID- 9993043 TI - Electronic structure of random alloys by the linear band-structure methods. PMID- 9993044 TI - Piezo-Raman measurements and anharmonic parameters in silicon and diamond. PMID- 9993045 TI - Exchange interaction and polariton effects in quantum-well excitons. PMID- 9993047 TI - Phase memory of the electronic polarization in transient nonlinear optical spectra of gallium arsenide at 2 eV. PMID- 9993046 TI - Adatom registry on Si(111)-( sqrt 3 x sqrt 3 )R30 degrees-B. PMID- 9993048 TI - Calculation of the intersubband absorption strength in ellipsoidal-valley quantum wells. PMID- 9993050 TI - Unrelaxation of the semiconductor surface at low-coverage Ag/InP(110) interfaces as determined by photoemission extended x-ray-absorption fine structure. PMID- 9993049 TI - Silicon valence states in calcium silicides: A Si L2,3VV Auger line-shape analysis. PMID- 9993051 TI - Semiempirical electronic-structure calculations of the hydrogen-phosphorus pair in silicon. PMID- 9993053 TI - Direct and indirect transition in (GaAs)n/(AlAs)n superlattices with n=1-15. PMID- 9993052 TI - Electronic and structural properties of CaSi2. PMID- 9993054 TI - Determination of accurate critical-point energies and linewidths from optical data. PMID- 9993055 TI - Effective masses and sum rules in strained Si/Ge structures. PMID- 9993056 TI - Nonreciprocal diffraction via grating coupling to surface magnetoplasmons. PMID- 9993057 TI - Analytical results for semiconductor quantum-well wire: Plasmons, shallow impurity states, and mobility. PMID- 9993058 TI - Effects of acoustic- and optical-phonon sidebands on the fundamental optical absorption edge in crystals and disordered semiconductors. PMID- 9993059 TI - Effects of wave-function delocalization on the optical properties of GaAs/AlAs short-period asymmetric superlattices. PMID- 9993060 TI - Theory of the fractional quantum Hall effect. PMID- 9993061 TI - Theoretical study of native defects and impurities in InP. PMID- 9993062 TI - Optically induced magnetization and Mn spin-lattice relaxation in InP:Mn. PMID- 9993063 TI - Photoluminescence and stimulated emission from monolayer-thick pseudomorphic InAs single-quantum-well heterostructures. PMID- 9993064 TI - Effects of inversion asymmetry on electron energy band structures in GaSb/InAs/GaSb quantum wells. PMID- 9993065 TI - Electronic structure of Si(111)-B( sqrt 3 x sqrt 3 )R30 degrees studied by Si 2p and B 1s core-level photoelectron spectroscopy. PMID- 9993066 TI - Dimensional quantization in a-Si:H quantum-well structures: The alloy model. PMID- 9993067 TI - Electronic properties of sulfur-treated GaAs(001) surfaces. PMID- 9993068 TI - Electron-LO-phonon scattering rates in semiconductor quantum wells. PMID- 9993069 TI - Photoconductivity relaxation in ZnIn2Se4. PMID- 9993070 TI - Spin splitting in n-type Bi1-xSbx alloys including doped bismuth (0 <= x <= 0.12). PMID- 9993071 TI - Phase transition in the fractional quantum Hall effect. PMID- 9993072 TI - Theory of local bond-length relaxation in Hg1-xCdxTe alloys. PMID- 9993073 TI - Strain effects in chemically lifted GaAs thin films. PMID- 9993074 TI - Thermodynamic and elastic properties of a many-body model for simple oxides. PMID- 9993075 TI - Lattice-dynamics and network-dynamics studies of vibrational modes in lithium doped borate glasses. PMID- 9993076 TI - Polarized Raman study of NO2- in KCl, KBr, KI, and NaBr. PMID- 9993077 TI - Low-temperature properties of a model glass. I. Elastic dipole model. PMID- 9993078 TI - Low-temperature properties of a model glass. II. Specific heat and thermal transport. PMID- 9993079 TI - Effects of pressure and isotopic substitution on the Raman spectrum of alpha Fe2O3: Identification of two-magnon scattering. PMID- 9993081 TI - Asymptotic solutions for localized vibrational modes in strongly anharmonic periodic systems. PMID- 9993080 TI - Generation mechanism of photoinduced paramagnetic centers from preexisting precursors in high-purity silicas. PMID- 9993082 TI - Defect-mediated hydrogen-bond melting in B-DNA polymers. PMID- 9993084 TI - Effects of localization and mesoscopic phenomena on ultrasonic attenuation in a disordered piezoelectric metal. PMID- 9993083 TI - Plasmon dispersion relation of a quasi-one-dimensional electron gas. PMID- 9993086 TI - Configuration-lattice approach to electron spectroscopies: Application to inverse photoemission. PMID- 9993085 TI - Electromagnetic-field-enhanced desorption of atoms. PMID- 9993087 TI - Transverse magnetic field studies in Al1-yInyAs/Ga1-xInxAs quantum-well tunneling structures. PMID- 9993089 TI - Good semiconductor band gaps with a modified local-density approximation. PMID- 9993088 TI - Single-particle and transport scattering times in narrow GaAs/AlxGa1-xAs quantum wells. PMID- 9993090 TI - Nature of the long-range order in the quantum Hall effect regime. PMID- 9993092 TI - Path-integral approach to resonant tunneling. PMID- 9993091 TI - Calculations of the structural properties of cubic zinc sulfide. PMID- 9993093 TI - Equations of state of alkali hydrides at high pressures. PMID- 9993094 TI - Comment on "Excitation-energy dependence of optically induced ESR in a-Si:H" PMID- 9993096 TI - Soft self-consistent pseudopotentials in a generalized eigenvalue formalism. PMID- 9993095 TI - Erratum: Exact theories for light, x-ray, electron, and neutron diffractions from planar media with periodic structures PMID- 9993097 TI - Structure determination of Cu(100)-p(2 x 2)-S using x-ray diffraction. PMID- 9993098 TI - Spin-flip relaxation time of conduction electrons in Cd1-xMnxTe quantum wells. PMID- 9993099 TI - Electronic properties of HgTe-CdTe superlattices with nonideal interfaces. PMID- 9993100 TI - Quantized transmission of a saddle-point constriction. PMID- 9993101 TI - Evidence for a spin transition in the nu =2/3 fractional quantum Hall effect. PMID- 9993103 TI - Role of photocurrent in low-temperature photoemission studies of Schottky-barrier formation. PMID- 9993102 TI - Probing island growth and coalescence at metal-semiconductor interfaces. PMID- 9993104 TI - Influence of localization on the Hall effect in narrow-gap, bulk semiconductors. PMID- 9993105 TI - Photoluminescence from excitons bound to a triple acceptor, Ge:Cu. PMID- 9993106 TI - Potential fluctuations in heterostructure devices. PMID- 9993107 TI - Interchain dynamics and side-group modulation of excitons in a polydiacetylene. PMID- 9993108 TI - Electrostatic electron lens in the ballistic regime. PMID- 9993109 TI - Acoustic interference in random superlattices. PMID- 9993111 TI - Charge-density-wave narrow-band noise in NbSe3 at T<4 K. PMID- 9993110 TI - Dispersive diffusion of hydrogen in a-Si:H: Influence of the film deposition temperature. PMID- 9993112 TI - Chemical-equilibrium model of optimal a-Si:H growth from SiH4. PMID- 9993113 TI - Ab initio study of localization and excitation of an excess electron in alkali halide clusters. PMID- 9993114 TI - Two-photon resonant effect of hyper-Raman scattering in the vicinity of the direct forbidden gap in a rutile crystal. PMID- 9993115 TI - Low-temperature growth of MgO by molecular-beam epitaxy. PMID- 9993116 TI - Optical transmissivity of superlattices with nonlinear magnetic susceptibility and absorption. PMID- 9993117 TI - Effect of disorder on the electronic structure of palladium. PMID- 9993119 TI - Many-particle effects at core thresholds in simple metals. PMID- 9993118 TI - Comparative analysis of Nd3+(4f3) energy levels in four garnet hosts. PMID- 9993120 TI - Effect of complete oxidation on the vibrational properties of aluminum oxide thin films: An electron-energy-loss-spectroscopy study. PMID- 9993121 TI - Strong one-dimensional localization in systems with statistically rough boundaries. PMID- 9993122 TI - Method for the calculation of excitonic effects in the absorption spectra of some metals. PMID- 9993123 TI - Localization problem in optics: Nonlinear quasiperiodic media. PMID- 9993124 TI - Molecular-dynamics studies of the thermal properties of the solid and liquid fcc metals Ag, Au, Cu, and Ni using many-body interactions. PMID- 9993126 TI - Experimental band structure of potassium as measured by angle-resolved photoemission. PMID- 9993125 TI - Defects in heteroepitaxial structures studied with monoenergetic positrons: Large lattice-mismatch systems Cu/Ag(111) and Ag/Cu(111). PMID- 9993127 TI - Balance-equation theory for steady-state resistivity. PMID- 9993128 TI - Toward a magnetic description of metals in terms of interstitial molecular orbitals: Exploiting the multiplicity of symmetry-broken Hartree-Fock solutions on small alkali-metal clusters. PMID- 9993129 TI - Spontaneous decay and resonance fluorescence of an admolecule near a silver surface with random roughness. PMID- 9993130 TI - Segregation in thin films of binary alloys AxB1-x. PMID- 9993131 TI - Interatomic contributions to molecular x-ray emission rates. PMID- 9993132 TI - Inelastic spin-exchange scattering of electrons from paramagnetic metals. PMID- 9993133 TI - Structural energy-volume relations in first-row transition metals. PMID- 9993134 TI - Scattering-matrix formulation of curved-wave multiple-scattering theory: Application to x-ray-absorption fine structure. PMID- 9993135 TI - Inverse photoemission from alkali-metal films. PMID- 9993136 TI - Diffuse elastic scattering of atoms from surface steps. PMID- 9993137 TI - Tunable-diode-laser infrared reflection absorption spectroscopy of carbon monoxide on Pt(111). PMID- 9993138 TI - Theoretical study of magnetism in iron, cobalt, and nickel. PMID- 9993139 TI - Influence of surface corrugations on hydrogenic image-potential states. PMID- 9993141 TI - Momentum noise in vacuum tunneling transducers. PMID- 9993140 TI - Properties of a substitutional and/or interstitial surface hydrogen atom. PMID- 9993142 TI - Identification of valence subbands in CdTe-Cd1-xZnxTe strained-layer quantum wells by differential spectroscopy. PMID- 9993143 TI - Two-dimensional Si crystal growth during thermal annealing of Au/polycrystalline Si bilayers. PMID- 9993145 TI - Optical properties of shallow defect-related acceptors in GaAs grown by molecular beam epitaxy. PMID- 9993144 TI - Kinetic study of Si recrystallization in the reaction between Au and polycrystalline-Si films. PMID- 9993146 TI - Donor spectroscopy in Hg1-xCdxTe at high magnetic fields. PMID- 9993147 TI - First-principles calculation of temperature-composition phase diagrams of semiconductor alloys. PMID- 9993148 TI - Conduction-band structure and charge-density waves in 1T-TaS2. PMID- 9993149 TI - Zero-field spin splitting in a two-dimensional electron gas. PMID- 9993150 TI - Band-gap renormalization in semiconductor quantum wells. PMID- 9993151 TI - Maximum low-temperature mobility of two-dimensional electrons in heterojunctions with a thick spacer layer. PMID- 9993152 TI - Planar force-constant method for lattice dynamics of superstructures. PMID- 9993153 TI - Hysteresis and Franck-Condon relaxation in insulator-semiconductor tunneling. PMID- 9993155 TI - Lattice-distortion-induced electronic bistability of the donor defect in semiconductors. PMID- 9993154 TI - Exchange effects in a quasi-one-dimensional electron gas. PMID- 9993156 TI - Deformation potentials at the top of valence bands in semiconductors: Ab initio pseudopotential calculations. PMID- 9993157 TI - Thomas-Fermi theory of delta -doped semiconductor structures: Exact analytical results in the high-density limit. PMID- 9993158 TI - CoSi2(111), FeSi2(001), and MoSi2(001) surfaces and interfaces with Ti. PMID- 9993159 TI - Interface dependence of band offsets in lattice-matched isovalent heterojunctions. PMID- 9993160 TI - Effect of fluorine on the structural and electronic properties of a-Si:H:F. PMID- 9993161 TI - Resonance of the magnetophonon conductivity in two-dimensional systems. PMID- 9993162 TI - Piezomodulated reflectivity spectra of GaAs/AlxGa1-xAs single-parabolic-quantum well heterostructures. PMID- 9993163 TI - Noise characteristics of double-barrier resonant-tunneling structures below 10 kHz. PMID- 9993164 TI - Properties of liquid arsenic: A theoretical study. PMID- 9993166 TI - Electronic-structure calculations of the Cr/GaAs(001) interface. PMID- 9993165 TI - Calculation of defect states in semiconductor crystals by recursion method. PMID- 9993168 TI - Band nonparabolicities in lattice-mismatch-strained bulk semiconductor layers. PMID- 9993167 TI - Role of lattice mismatch and surface chemistry in the formation of epitaxial semiconductor-insulator interfaces. PMID- 9993169 TI - Extended x-ray-absorption fine-structure studies of Zn1-xMnxSe alloy structure. PMID- 9993170 TI - Fractional quantum Hall effect in very-low-density GaAs/AlxGa1-xAs heterostructures. PMID- 9993171 TI - Magnetoconductance of two point contacts in series. PMID- 9993172 TI - Metal-InP(110) interface properties: Temperature, dopant-concentration, and cluster-deposition dependencies. PMID- 9993174 TI - Energy level associated with the DX center in Ga1-xAlxAs. PMID- 9993173 TI - Hopping transport in delta -doping layers in GaAs. PMID- 9993175 TI - Theory of two-dimensional grating couplers. PMID- 9993176 TI - Growth of alkali halides by molecular-beam epitaxy. PMID- 9993177 TI - Effect of electron-density discontinuity on magnetotransport in multiprobe narrow channel structures. PMID- 9993178 TI - Oxygen-nickel bond length in Ni(111)-p(2 x 2)O determined by electron-energy-loss fine-structure spectroscopy. PMID- 9993179 TI - Anomalous broadening of angle-resolved photoemission linewidths on W(011). PMID- 9993180 TI - Negative surface-plasmon dispersion coefficient: A physically illustrative, exact formula. PMID- 9993182 TI - Scarcity of icosahedra in quenched simple atomic liquids. PMID- 9993181 TI - Theory of the incommensurate-to-commensurate transition in long-period superlattices of A3B-type alloys. PMID- 9993184 TI - Path-integral approach to transient transport of a double-barrier resonant tunneling system. PMID- 9993183 TI - Structural information on island metal films from aging measurements. PMID- 9993185 TI - Temperature dependence of mobility in AlxGa1-xAs/GaAs heterostructures for impurity scattering. PMID- 9993186 TI - Optical absorption of ZnGa2S4 and ZnGa2S4:Co2+ crystals. PMID- 9993187 TI - Fourier-transform analysis of multiexponential curves observed in photoconductivity studies. PMID- 9993188 TI - Van Hove anomaly in the phonon dispersion of monolayer Ar/Pt(111). PMID- 9993189 TI - Electrochemical-potential variations across a constriction. PMID- 9993190 TI - Hall effect in a single two-dimensional quasicrystal: Al62Si3Cu20Co15. PMID- 9993191 TI - Electron paramagnetic resonance identification of the orthorhombic iron-indium pair in silicon. PMID- 9993192 TI - Long-lived spatially indirect excitons in coupled GaAs/AlxGa1-xAs quantum wells. PMID- 9993193 TI - Electron minibands and Wannier-Stark quantization in an In0.15Ga0.85As-GaAs strained-layer superlattice. PMID- 9993194 TI - Low-field magnetotransport in p-type GaAs in the regime of variable-range-hopping conductivity. PMID- 9993195 TI - Four-wave mixing of Nd3+-doped crystals and glasses. PMID- 9993196 TI - Channeling of MeV ions in polyatomic epitaxial films: ReSi2 on Si(100). PMID- 9993197 TI - One-phonon coherent, resonant scattering of neutrons by harmonic crystals. PMID- 9993198 TI - 57Fe Mossbauer studies of Nd2Fe14B and Nd2Fe12.5Si1.5B (T=77-300 K). PMID- 9993199 TI - Perturbed-angular-distribution measurements of the chemical shift of iron in the disulfides FeS2 (pyrite) and RuS2 (laurite). PMID- 9993200 TI - Chain character of vacancy-type defects in silicon. PMID- 9993201 TI - Deuteron polarization of solid DT. PMID- 9993202 TI - Nuclear magnetic resonance on oriented 99mRh and 101mRh in Ni. PMID- 9993203 TI - Spectral transport of nonequilibrium 29-cm-1 phonons in ruby studied by fluorescence line narrowing. PMID- 9993204 TI - Dielectric response and self-energy in Hubbard systems. PMID- 9993205 TI - Angle-resolved photoelectron spectra of (Bi1-xPbx)2Sr2CaCu2O8 and their line shape analysis. PMID- 9993207 TI - Phase diagram and low-temperature behavior of oxygen ordering in YBa2Cu3Oz using ab initio interactions. PMID- 9993206 TI - Superconductivity in the homogeneous electron gas: Exchange and correlation effects. PMID- 9993209 TI - Normal and antiferromagnetic states of an extended Hubbard model. PMID- 9993208 TI - Hole-quasiparticle band narrowing in the two-dimensional t-J model. PMID- 9993210 TI - Thermoelectric power of high-Tc superconductors. PMID- 9993212 TI - Monte Carlo simulations of Josephson-junction arrays with positional disorder. PMID- 9993211 TI - Elementary excitations in superfluid 3He-4He mixtures: Pressure and temperature dependence. PMID- 9993213 TI - Superconductivity under high pressure of YBa2(Cu1-xMx)3O7- delta (M=Fe, Co, Al, Cr, Ni, and Zn). PMID- 9993214 TI - Soliton statistics for critical temperature of superconductivity in organic quasi one-dimensional crystals. PMID- 9993215 TI - Dependence of the second upper critical field on coupling strength. PMID- 9993217 TI - Raman-active phonons of a twin-free YBa2Cu3O7 crystal: A complete polarization analysis. PMID- 9993216 TI - Numerical investigation of a model for oxygen ordering in YBa2Cu3O6+x. PMID- 9993218 TI - Theory of Raman scattering with final-state interaction in high-Tc BCS superconductors: Collective modes. PMID- 9993219 TI - Two-body density matrix of a normal Fermi fluid. PMID- 9993220 TI - Electronic structure of undoped and doped La2CuO4: A Hartree-Fock cluster study. PMID- 9993221 TI - Effect of microstructural changes on thermally activated flux-creep behavior in the Bi-Sr-Ca-Cu-O system. PMID- 9993223 TI - Pulsed-laser evaporation technique for deposition of thin films: Physics and theoretical model. PMID- 9993222 TI - ac susceptibility and grain-boundary pinning strengths in YBa2Cu3O7- delta and YBa2Cu2.985Ag0.015O7- delta. PMID- 9993224 TI - Frequency mixing in de Haas-van Alphen oscillations in heavy-fermion compounds. PMID- 9993226 TI - New pairing state in an attractively coupled double-chain organic material: Possibility of an exciton mechanism of superconductivity in spatially separated systems. PMID- 9993225 TI - Muon-spin-relaxation and neutron-scattering studies of magnetism in single crystal La1.94Sr0.06CuO4. PMID- 9993227 TI - Reflection of hydrogen atoms from the surface of superfluid helium. PMID- 9993229 TI - Tunneling spectroscopy study of YBa2Cu3O7 thin films using a cryogenic scanning tunneling microscope. PMID- 9993228 TI - Vortex states in an unconventional superconductor and the mixed phases of UPt3. PMID- 9993230 TI - Dilute-bounce-gas approximation in the dissipative double-well system. PMID- 9993231 TI - Ba core-level shift in x-ray photoemission spectroscopy on single-phase Y1 xPrxBa2Cu3O7 and YBa2Cu3O7-y compounds. PMID- 9993232 TI - Dynamic simulations of arrays of Josephson junctions. PMID- 9993233 TI - Fundamental and harmonic susceptibilities of YBa2Cu3O7- delta. PMID- 9993234 TI - Self-consistent antiferromagnetic ground state for La2CuO4 via energy-band theory. PMID- 9993235 TI - Determination of the valence of Pr, Gd, and Ho in YBa2Cu3O7 by x-ray absorption spectroscopy. PMID- 9993236 TI - Filled-band model leading to supercurrents in La-Ba-Cu-O. PMID- 9993237 TI - States in the superconductive energy gap of high-Tc cuprates. PMID- 9993238 TI - Temperature and frequency dependences of the dielectric properties of YBa2Cu3O6+x (x PMID- 9993240 TI - Thermal fluctuations of vortex lines, pinning, and creep in high-Tc superconductors. PMID- 9993239 TI - Ultrasonic study of structural instability of monocrystalline and polycrystalline Bi-Sr-Ca-Cu-O. PMID- 9993242 TI - Coexistence curve of methanol+n-heptane: Range of simple scaling and critical amplitudes. PMID- 9993241 TI - Spin-disordered ground state for a nearly half-filled Hubbard model. PMID- 9993243 TI - Density-of-states-driven transition from superconductivity to ferromagnetism in Ce(Ru1-xRhx)3B2: Scenario for an exchange-split Kondo resonance. PMID- 9993245 TI - Fractional quantum Hall effect in nonuniform magnetic fields. PMID- 9993244 TI - Effects of sulfur vacancies on the crystallographic and spin-rotation transitions of iron sulfide. PMID- 9993246 TI - Critical behavior of the layer compressional elastic constant B at the smectic-A nematic phase transition. PMID- 9993247 TI - Spin conversion of tunneling CH3 rotors in copper acetate. PMID- 9993248 TI - Magnetic susceptibility of californium fluorides. PMID- 9993249 TI - Strongly correlated electronic systems with one hole: Dynamical properties. PMID- 9993250 TI - Magnetic and structural properties of Mn(SCN)2(CH3OH)2: A quasi-two-dimensional Heisenberg antiferromagnet. PMID- 9993251 TI - Theoretical aspects of the magnetism in the ferromagnetic AFe2 systems (A=U, Np, Pu, and Am). PMID- 9993252 TI - Orbital magnetism in the itinerant ferromagnet NpOs2. PMID- 9993253 TI - Density of states based on dimensional dilution symmetry for disordered hypercubic lattices. PMID- 9993254 TI - Theory of ferromagnetism in CeCo5. PMID- 9993255 TI - Simulation study of roughening in disordered systems. PMID- 9993256 TI - Singlet-exciton transport and spatial and energetic disorder in dibenzofuran crystals. PMID- 9993257 TI - Magnetic static and scaling properties of the weak random-axis magnet (DyxY1 x)Al2. PMID- 9993258 TI - Lattice model of microemulsions. PMID- 9993260 TI - Systematic study on antiferromagnetic states of the Hubbard model with the dimension d=1, 2, 3 and PMID- 9993259 TI - Structural transition on W(100). PMID- 9993261 TI - Stabilization of flux states on two-dimensional lattices. PMID- 9993263 TI - Finite-temperature theory of local environment effects in amorphous and liquid magnetic alloys. PMID- 9993262 TI - Series study of percolation moments in general dimension. PMID- 9993264 TI - Quantum Heisenberg spin glasses: Anisotropy effects and field dependence. PMID- 9993265 TI - Magnon damping in the two-dimensional quantum Heisenberg antiferromagnet at short wavelengths. PMID- 9993266 TI - Theory of ordering dynamics for Cu3Au. PMID- 9993267 TI - Finite-size scaling of the Ising model in four dimensions. PMID- 9993268 TI - Three-band Hubbard model: A Monte Carlo study. PMID- 9993270 TI - Possible mechanism for limiting the number of modes in spin-wave instabilities in parallel pumping. PMID- 9993269 TI - Isotropic compression of the linear-chain perovskite-type CsCdBr3 up to 20 GPa. PMID- 9993271 TI - Magnetic excitations in USn3. PMID- 9993273 TI - Spin-density-wave and charge-density-wave fluctuation and electric conductivity. PMID- 9993272 TI - Sign problem in the numerical simulation of many-electron systems. PMID- 9993274 TI - Magnetic, specific-heat, and resistivity measurements of alloys CePd2-x+yMnxSi2-y (0 <= x <= 2, -0.1 <= y <= 0.1). PMID- 9993275 TI - Bond-operator representation of quantum spins: Mean-field theory of frustrated quantum Heisenberg antiferromagnets. PMID- 9993276 TI - Anisotropic thermal-lens effect in ferroelectric Ba2NaNb5O15 at Tc. PMID- 9993278 TI - Random walks in percolating networks with two jump frequencies. PMID- 9993277 TI - Elucidation of the specific-heat anomaly below TN in NpIr2. PMID- 9993279 TI - Monte Carlo calculations on antiferromagnetic Ising particles. PMID- 9993281 TI - Fermions and solitons in the O(3) nonlinear sigma model in 2+1 space-time dimensions. PMID- 9993280 TI - Specific heat of UPt3 in magnetic fields up to 24.5 T. PMID- 9993282 TI - Finite-size studies of phases and dimerization in one-dimensional extended Peierls-Hubbard models. PMID- 9993284 TI - Thermodynamics of the infinite-U Hubbard model. PMID- 9993283 TI - Ground-state degeneracy of the fractional quantum Hall states in the presence of a random potential and on high-genus Riemann surfaces. PMID- 9993286 TI - Rank-four spin-Hamiltonian parameters of a 3d5 ion. PMID- 9993285 TI - Renormalization-group calculation of excitation properties for impurity models. PMID- 9993288 TI - Scattering from a magnetic strip: Analytic description of transmission and conductance. PMID- 9993287 TI - Critical property and universality in the generalized Smoluchovski coagulation equation. PMID- 9993289 TI - Phase diagram of the extended Hubbard model in one spatial dimension. PMID- 9993291 TI - Gutzwiller correlated wave functions in finite dimensions d: A systematic expansion in 1/d. PMID- 9993290 TI - Calculation of magnetic impurities in a nonmagnetic host: Fe in Au. PMID- 9993292 TI - Finite-size study of a spin-1/2 Heisenberg chain with competing interactions: Phase diagram and critical behavior. PMID- 9993293 TI - Computer-simulation study of melting in dense oxygen layers on graphite. PMID- 9993294 TI - Ground-state quantum numbers of the half-filled Hubbard model. PMID- 9993296 TI - Holes in Heisenberg antiferromagnets. PMID- 9993295 TI - Magic-angle spinning 29Si NMR study of short-range order in a-Si. PMID- 9993297 TI - Anomalous behavior of phonons in superconducting Tl2Ba2Ca2Cu3O10 detected by far infrared spectroscopy. PMID- 9993298 TI - Local structural variations near twins in YBa2Cu3O7- delta. PMID- 9993299 TI - Homogeneous and fractal behavior of superconducting fluctuations in the electrical resistivity of granular ceramic superconductors. PMID- 9993300 TI - Bean's, Kim's, and exponential critical-state models for high-Tc superconductors. PMID- 9993301 TI - 89Y NMR study of the exchange coupling constant between the CuO2 layer and the Gd ion in GdxY1-xBa2Cu3O7- delta. PMID- 9993302 TI - Analysis of the specific-heat anomalies of K2SeO4 and Rb2ZnCl4 near the normal incommensurate phase transition. PMID- 9993304 TI - Stability of an icosahedral incommensurate phase formed in an immiscible alloy system. PMID- 9993303 TI - Pb/Ge(111)1 x 1: An anisotropic two-dimensional liquid. PMID- 9993305 TI - Peierls stabilization of magnetic-flux states of two-dimensional lattice electrons. PMID- 9993306 TI - Determination of the order of phase transitions in numerical simulations. PMID- 9993307 TI - Low-temperature specific heat of glasses: Quantum Monte Carlo simulation of a strongly anharmonic oscillator. PMID- 9993309 TI - Erratum: "Structure of an isolated vortex in an anisotropic type-II superconductor" PMID- 9993308 TI - Comment on "Surfaces and interfaces of lattice models: Mean-field theory as an area-preserving map" PMID- 9993310 TI - Multiply charged ions from electron bombardment of SiO2. PMID- 9993312 TI - Skew-scattering effect on the Hall-conductance fluctuation in high-temperature superconductors. PMID- 9993311 TI - Time spectra of a nearly-single-line pure nuclear reflection excited by synchrotron radiation. PMID- 9993314 TI - Charge and spin dynamics in a doped quantum antiferromagnet. PMID- 9993313 TI - High-pressure study of Bi2Sr2CaCu2O8 single crystals. PMID- 9993315 TI - Photoelectron spectroscopic study of (Y1-xCax)Ba2Cu4Oy: Observation of the Fermi edge-like structure at room temperature. PMID- 9993316 TI - Low-temperature properties of the quasi-two-dimensional antiferromagnetic Heisenberg model. PMID- 9993317 TI - Anisotropic and thermally activated resistive behavior in Nd1.85Ce0.15CuO4- delta. PMID- 9993318 TI - 17O NMR spectroscopy of Bi2Sr2CaCu2O8+x high-Tc superconductor. PMID- 9993320 TI - Phase transition in the generalized Fibonacci quantum Ising models. PMID- 9993319 TI - 63Cu NMR shift and linewidth anomalies in the Tc=60 K phase of Y-Ba-Cu-O. PMID- 9993321 TI - Isotope effect on displacive-type ferroelectric-phase-transition temperatures. PMID- 9993323 TI - Thermodynamic properties of a quantum chain with nearest-neighbor anharmonic interactions. PMID- 9993322 TI - Giant transverse hysteresis in an asperomagnet. PMID- 9993324 TI - Spin-Peierls transitions in S>1/2 Heisenberg chains. PMID- 9993325 TI - Critical spin fluctuations and Curie temperatures of ultrathin Ni(111)/W(110): A magnetic-resonance study in ultrahigh vacuum. PMID- 9993326 TI - Calculation of Invar anomalies. PMID- 9993327 TI - Anyons in the XY model induced by charged holes. PMID- 9993328 TI - Formation of an anisotropic energy gap in the valence-fluctuating system of CeNiSn. PMID- 9993329 TI - Exact lower bounds to the ground-state energy of spin systems: The two dimensional S=1/2 antiferromagnetic Heisenberg model. PMID- 9993330 TI - Formation of fractal patterns of MoO3 crystals during phase transformation. PMID- 9993331 TI - Instability of ferromagnetism at finite hole density in the U= PMID- 9993332 TI - Critical temperature of an Ising magnetic film. PMID- 9993333 TI - Anisotropic transport properties of a stable two-dimensional quasicrystal: Al62Si3Cu20Co15. PMID- 9993334 TI - Thermal-expansion and index-of-refraction variation in lead fluoride between 300 and 850 K. PMID- 9993335 TI - Physical adsorption near an oblique corner. PMID- 9993336 TI - Method of obtaining the empirical scattering parameters for the Fe-B pair from the extended x-ray-absorption fine-structure data of Fe2B: Possible limitations. PMID- 9993337 TI - Spin-polarized photoemission studies of the adsorption of O and S on Fe(001). PMID- 9993339 TI - Geometry of the ND3 group in a metallic Ca(ND3)6 compound and in solid and liquid deuteroammonia as measured by neutron scattering. PMID- 9993338 TI - Correlation effects in the extended x-ray-absorption fine-structure Debye-Waller factors of AgI. PMID- 9993340 TI - Linear combination of Gaussian-type orbitals-local-density-functional cluster studies of D-D interactions in titanium and palladium. PMID- 9993341 TI - Adsorption of Li (K) on the Si(001)-(2 x 1) surface: Scanning-tunneling microscopy study. PMID- 9993343 TI - Electronic structure and magnetism of R2Fe14B (R=Y,Nd) compounds. PMID- 9993342 TI - Structure analysis of the Cu(110)-(1 x 2) surface reconstruction induced by alkali-metal adsorption. PMID- 9993344 TI - Total-energy and pressure calculations for random substitutional alloys. PMID- 9993345 TI - Phase stability of fcc alloys with the embedded-atom method. PMID- 9993346 TI - Low-temperature specific heat and resistivity of single-crystalline Pd2Si. PMID- 9993347 TI - Hopping conduction on an imperfect Fibonacci lattice. PMID- 9993348 TI - Phase coherence and the effect of an ac electric field on the conductance of a disordered one-dimensional system. PMID- 9993350 TI - Magnetic properties of stage-1 CoCl2-graphite intercalation compounds diluted with MgCl2. PMID- 9993349 TI - Phonon propagation with isotope scattering and spontaneous anharmonic decay. PMID- 9993351 TI - Band-structure effects in secondary-electron-emission and absorbed-current spectra of (111), (100), and (110) surfaces of silver. PMID- 9993352 TI - Electronic structure of an ideal diamond-nickel (001) interface. PMID- 9993353 TI - Lifetime and screening of the C 1s photoemission in graphite. PMID- 9993355 TI - Inelastic scattering from Einstein modes of surface defects. PMID- 9993354 TI - Nitrogen valence electronic structure in the strong chemisorption limit: Molecular adsorption on Cr(110) and O/Cr(110). PMID- 9993356 TI - Thin Hf layers in Nb studied by the perturbed angular correlation method. I. Characterization of thin layers in Nb-Hf-Nb layered structures. PMID- 9993358 TI - Asymptotic estimation of Hankel transforms and the screened Coulomb potential in trilayer structures. PMID- 9993357 TI - Thin Hf layers in Nb studied by the perturbed angular correlation method. II. The effect of hydrogen on the Nb-Hf-Nb samples. PMID- 9993359 TI - Critical structure in the density of states from non-atom-centered Wannier functions. PMID- 9993361 TI - Schottky-barrier behavior of copper and copper silicide on n-type and p-type silicon. PMID- 9993360 TI - Scaling in the growth of aggregates on a surface. PMID- 9993362 TI - Surface phase transitions on clean Ge(111) studied by spectroscopic ellipsometry. PMID- 9993363 TI - Model based on trap-assisted tunneling for two-level current fluctuations in submicrometer metal-silicon-dioxide-silicon diodes. PMID- 9993364 TI - Band offsets for strained InxGa1-xAs/AlyGa1-yAs heterointerfaces. PMID- 9993365 TI - Stress splitting of the EL2 zero-phonon line: Need for reinterpretation of the main optical transition. PMID- 9993366 TI - Pressure coefficient of the direct band gap of the solid solution ZnxCd1-xS. PMID- 9993367 TI - Formation of Si(111)-(1 x 1)Cl. PMID- 9993368 TI - Photoluminescence above the Tauc gap in a-Si:H. PMID- 9993369 TI - Direct determination of III-V semiconductor surface band gaps. PMID- 9993370 TI - Interstitial O in Si and its interactions with H. PMID- 9993371 TI - Resonant tunneling with a time-dependent voltage. PMID- 9993372 TI - Monte Carlo study of the transient expansion of photogenerated plasmas in bulk semiconductors: Nonequilibrium phonon effects. PMID- 9993373 TI - Relocation of Si atoms in kilo-electron-volt and mega-electron-volt Si-ion irradiation of crystalline Si. PMID- 9993374 TI - Structure of photodoped and thermally Zn-doped glassy arsenic sulfide films. PMID- 9993375 TI - Mutual drag of two- and three-dimensional electron gases in heterostuctures. PMID- 9993376 TI - X-ray analysis of the device structures of III-V compound semiconductors. PMID- 9993378 TI - Quantum statistics of polarized photoluminescence in ordered GaInP2. PMID- 9993377 TI - Anisotropy of surface optical properties from first-principles calculations. PMID- 9993379 TI - Photoexcited quantum wells: Nonlinear screening, bistability, and negative differential capacitance. PMID- 9993380 TI - Electronic structure of GaAs(001). PMID- 9993382 TI - Positron trapping in semiconductors. PMID- 9993381 TI - Photoacoustic characterization of semiconductors: Transport properties and thermal diffusivity in GaAs and Si. PMID- 9993383 TI - Removal of accidental degeneracies in semiconductor quantum wires. PMID- 9993384 TI - Nonlinear optical response of two-dimensional magnetoexcitons. PMID- 9993385 TI - Dynamical properties of layered superionic conductors. PMID- 9993387 TI - Energy-level spectra of transition-metal ions in II-VI semiconductors. PMID- 9993386 TI - Quantum tunability of superlattice minibands. PMID- 9993388 TI - Density of states and optical-absorption spectra of shallow impurities in quantum wells under the influence of a longitudinal electric field. PMID- 9993389 TI - Thermal-equilibrium defects in undoped hydrogenated amorphous silicon, silicon carbon, and silicon-nitrogen. PMID- 9993390 TI - Quasiparticle band offset at the (001) interface and band gaps in ultrathin superlattices of GaAs-AlAs heterojunctions. PMID- 9993392 TI - Scanning tunneling microscopy of atoms and charge-density waves in 1T-TaS2, 1T TaSe2, and 1T-VSe2. PMID- 9993391 TI - Temperature dependence of direct transitions in angle-resolved photoemission and its application to InSb. PMID- 9993393 TI - Effect of pressure on the refractive index of Ge and GaAs. PMID- 9993394 TI - Effect of pressure on the low-temperature exciton absorption in GaAs. PMID- 9993395 TI - Recombination dynamics in pseudomorphic and partially relaxed In0.23Ga0.77As/GaAs quantum wells. PMID- 9993396 TI - Bulk and surface states of a doped superlattice. PMID- 9993397 TI - Raman scattering and hydrogen-content analysis of amorphous hydrogenated carbon films irradiated with 200-keV C+ ions. PMID- 9993398 TI - Tl+Tl0(1)-like dimer centers in KCl and RbCl doped with Tl+, In+, and Ga+: A resonant Raman study. PMID- 9993399 TI - Interpretation of features in the surface-phonon dispersion curves of KBr(001) and RbBr(001). PMID- 9993400 TI - Valence-band spectra of tin oxides interpreted by X alpha calculations. PMID- 9993401 TI - Lattice and central modes in the hyper-Raman spectra of the hydrogen-bonded ferroelectrics PbHPO4 and PbDPO4. PMID- 9993402 TI - Electronic structure of multiple vacancies in rutile TiO2 by the equation-of motion method. PMID- 9993403 TI - Novel magnetoresistance oscillations in a two-dimensional superlattice potential. PMID- 9993404 TI - Experimental probe for thin-film magnetism in p(1 x 1) Pd and V on Ag(100). PMID- 9993405 TI - Direct low-energy electron-diffraction analysis of c(2 x 2)O/Ni(100) including substrate reconstruction. PMID- 9993406 TI - H-H interaction in Ti lattice: Pseudopotential density-functional total-energy approach. PMID- 9993407 TI - Effect of surface state on the spin susceptibility of ultrafine metallic particles. PMID- 9993408 TI - Photon band structures: The plane-wave method. PMID- 9993409 TI - Different localization behavior of the wave functions of incommensurate systems. PMID- 9993410 TI - Linewidth behavior of the A1g Raman phonon in CdxHg1-xI2 solid solution. PMID- 9993411 TI - Step stability, domain coverage, and nonequilibrium kinetics in Si(001) molecular beam epitaxy. PMID- 9993412 TI - Subband-Landau-level coupling in the fractional quantum Hall effect in tilted magnetic fields. PMID- 9993414 TI - Disorder-induced Raman scattering in NiSi2. PMID- 9993413 TI - Strain splitting of the X-conduction-band valleys and quenching of spin-valley interaction in indirect GaAs/AlxGa1-xAs:Si heterostructures. PMID- 9993415 TI - Intraband optical absorption in semiconductor superlattices. PMID- 9993416 TI - Carrier scattering by native defects in heavily doped semiconductors. PMID- 9993417 TI - Plasmons on a randomly rough surface. PMID- 9993418 TI - Comment on "Exact eigenvalue equation for a finite and infinite collection of muffin-tin potentials" PMID- 9993419 TI - Reply to "Comment on 'Exact eigenvalue equation for a finite and infinite collection of muffin-tin potentials' " PMID- 9993420 TI - Erratum: Renormalized model for the dynamics of the krypton-on-graphite domain wall lattice PMID- 9993421 TI - Generation of microwave radiation in the tunneling junction of a scanning tunneling microscope. PMID- 9993422 TI - Surface reconstruction of Cu(110) induced by oxygen chemisorption. PMID- 9993424 TI - Log-normal distribution as a description of fluctuations in one-dimensional disordered systems. PMID- 9993423 TI - Image-potential-induced resonances at free-electron-like metal surfaces. PMID- 9993425 TI - Transferability of bulk empirical potentials to silicon microclusters: A critical study. PMID- 9993427 TI - Quantum transport and phonon emission of nonequilibrium hot electrons. PMID- 9993426 TI - Si(111)-5 x 1-Au reconstruction as studied by scanning tunneling microscopy. PMID- 9993429 TI - Role of hydrogen complexes in the metastability of hydrogenated amorphous silicon. PMID- 9993428 TI - Observation of nonradiative energy transfer in the excitation of Nd3+ luminescence in GaP. PMID- 9993430 TI - Incomplete confinement of electrons and holes in microcrystals. PMID- 9993432 TI - Plasmon excitations in one-dimensional lateral-quantum-wire superlattices. PMID- 9993431 TI - Valence-band offsets and formation enthalpy of reconstructed GaAs/Ge(001) interfaces. PMID- 9993433 TI - Infrared absorption of deep defects in molecular-beam-epitaxial GaAs layers grown at 200 degreesC: Observation of an EL2-like defect. PMID- 9993434 TI - Quasicontinuum of metal electronic states and the electronic properties of semiconductor-metal-semiconductor heterostructures. PMID- 9993435 TI - Observation of excitonic effects on electroabsorption in coupled quantum wells. PMID- 9993436 TI - Photoemission from metal dots on GaAs(110): Surface photovoltages and conductivity. PMID- 9993437 TI - Edge magnetoplasmons in the fractional-quantum-Hall-effect regime. PMID- 9993438 TI - Structural properties of ordered high-melting-temperature intermetallic alloys from first-principles total-energy calculations. PMID- 9993439 TI - Many-body potentials and atomic-scale relaxations in noble-metal alloys. PMID- 9993440 TI - Optical response of microscopically rough surfaces. PMID- 9993442 TI - Evanescent modes and scattering in quasi-one-dimensional wires. PMID- 9993441 TI - Harris functional and related methods for calculating total energies in density functional theory. PMID- 9993443 TI - Laser-induced thermomagnetic detection of a metastable band in bismuth. PMID- 9993444 TI - Dynamics of thin epitaxial layers on (001) surfaces of bcc metals: A Green function approach. PMID- 9993445 TI - Josephson superlattices and low-amplitude gap solitons. PMID- 9993446 TI - Structural characterization of precious-mean quasiperiodic Mo/V single-crystal superlattices grown by dual-target magnetron sputtering. PMID- 9993447 TI - Resonant photoemission at core-level shake-up thresholds: Valence-band satellites in nickel. PMID- 9993448 TI - Ground states of two-dimensional quasicrystals. PMID- 9993449 TI - First-principles, general-potential local-orbital calculations for bulk crystals. PMID- 9993450 TI - Theoretical study of the interaction of ionized transition metals (Cr,Mn,Fe,Co,Ni,Cu) with argon. PMID- 9993451 TI - Surface statistical thermodynamics and magnetic susceptibility in the infinite barrier model. PMID- 9993453 TI - Adsorbate-induced nonlocal corrections to Fresnel optics: Optical reflectivity of Cs overlayers on Ag. PMID- 9993452 TI - First-principles calculations of electronic structure in random hcp alloys: A Ru Re example. PMID- 9993454 TI - Subplantation model for film growth from hyperthermal species. PMID- 9993456 TI - Molecular-dynamics study of amorphization by introduction of chemical disorder in crystalline NiZr2. PMID- 9993455 TI - Ionic Hall effect in crystals: Independent versus cooperative hopping in AgBr and alpha -AgI. PMID- 9993457 TI - Stacking quasicrystallographic lattices. PMID- 9993458 TI - Normal electron-electron scattering in thin films at low temperatures: Anomalous surface impedance. PMID- 9993460 TI - Theory of Landau diamagnetism of dirty metals. PMID- 9993459 TI - Autoionization versus photoionization of molecular adsorbates: CO2 physisorbed on Ni(110). PMID- 9993461 TI - High sensitivity of umklapp components of momentum densities to the crystal potential and its consequences for the electron-positron enhancement factor. PMID- 9993462 TI - Magnetoresistivity studies of Zr-M amorphous alloys (M=Ni, Co, and Fe): From superconductivity to ferromagnetism. PMID- 9993463 TI - Orthogonalized linear combinations of atomic orbitals. IV. Inclusion of relativistic corrections. PMID- 9993464 TI - Stress theorem and Hellmann-Feynman relations for the jellium model of interfaces. PMID- 9993465 TI - Interatomic potential for silicon clusters, crystals, and surfaces. PMID- 9993467 TI - Oxygen-oxygen complexes and thermal donors in silicon. PMID- 9993466 TI - Optical excitations in poly(2,5-thienylene vinylene). PMID- 9993468 TI - Exchange-induced splitting of exciton energy levels in quantum wires. PMID- 9993469 TI - Electronic structure of zinc-blende-structure semiconductor heterostructures. PMID- 9993470 TI - Interaction of electrons with the confined LO phonons of a free-standing GaAs quantum wire. PMID- 9993471 TI - Guided and interface LO phonons in cylindrical GaAs/AlxGa1-xAs quantum wires. PMID- 9993472 TI - Native and irradiation-induced monovacancies in n-type and semi-insulating GaAs. PMID- 9993473 TI - Exchange correlation in the X alpha approximation and shallow-donor impurity ionization energy. PMID- 9993474 TI - Persistent photoconductivity and two-band effects in GaAs/AlxGa1-xAs heterojunctions. PMID- 9993475 TI - Electronic properties of the donor states under two-dimensional-conductor and quantum-wire configurations in heavily and orderly doped (GaAs)-(AlAs). PMID- 9993476 TI - Role of ring torsion angle in polyaniline: Electronic structure and defect states. PMID- 9993477 TI - Global adiabatic regime in quantum ballistic transport. PMID- 9993478 TI - Characterization of the electron gas in wide parabolic GaAs/AlxGa1-xAs quantum wells. PMID- 9993480 TI - Determination of band bending at the Si(113) surface from photovoltage-induced core-level shifts. PMID- 9993479 TI - Universal features in degenerate and nondegenerate hot-carrier screening. PMID- 9993481 TI - Structural properties and electronic structure of low-compressibility materials: beta -Si3N4 and hypothetical beta -C3N4. PMID- 9993483 TI - Concentration of native point defects in Si single crystals at high temperatures. PMID- 9993482 TI - Cluster calculations of ZnO with Cu and Ni impurities. PMID- 9993484 TI - Theoretical study of the vibrational spectra in poly(p-phenylene vinylene). PMID- 9993485 TI - Nonparabolicity of the conduction band in GaAs. PMID- 9993486 TI - Electronic processes in double-barrier resonant-tunneling structures studied by photoluminescence spectroscopy in zero and finite magnetic fields. PMID- 9993487 TI - Term spectrum of magnetoexcitons in quasi-two-dimensional systems. PMID- 9993489 TI - Nonequilibrium carrier processes in the presence of microwaves and magnetic fields in epitaxial GaAs studied by photoluminescence spectroscopy. PMID- 9993488 TI - Interaction of longitudinal-optic phonons with free holes as evidenced in Raman spectra from Be-doped p-type GaAs. PMID- 9993490 TI - Persistent photoconductivity in compensated amorphous silicon. PMID- 9993491 TI - Quantum levels and Zeeman splitting for two-dimensional hydrogenic donor states in a magnetic field. PMID- 9993492 TI - Laser spectroscopic measurement of point-defect dynamics in Eu3+:CaF2. PMID- 9993493 TI - Lattice dynamics of ionic crystals. PMID- 9993494 TI - Relationship between hyperfine parameters and the geometry of defects in nonmetallic solids. PMID- 9993495 TI - Lattice dynamics with indirect ionic interactions. PMID- 9993496 TI - Nonradiative energy transfer from Cu+ to Mn2+ ions in monocrystalline NaCl. PMID- 9993497 TI - Hole mobilities in films of a pyrazoline:polycarbonate molecularly doped polymer. PMID- 9993498 TI - First- and second-order resonant Raman scattering in graphite. PMID- 9993499 TI - Surface melting of Pb(110) studied by x-ray photoelectron diffraction. PMID- 9993500 TI - Low-temperature heat capacity of Pd0.35Zr0.65Dx (x=0.00-0.80) metallic glasses. PMID- 9993501 TI - Low-density quantum plasmas: Semiclassical screening oscillations. PMID- 9993502 TI - Quenching of the Hopkinson maximum under contamination in the system Gd(0001)/W(110). PMID- 9993503 TI - Spin-reversed excitations in the fractional quantum Hall effect. PMID- 9993504 TI - Interatomic potentials and the structural properties of silicon dioxide under pressure. PMID- 9993505 TI - Lattice-simulation investigations of the migration of lithium in intercalated graphite. PMID- 9993507 TI - Effect of nonmagnetic impurities on the residual electron-spin-resonance linewidth of Er:Ag dilute alloys. PMID- 9993506 TI - Temperature-induced intraband transitions in the n-type HgTe/CdTe superlattice. PMID- 9993508 TI - Ni2+ ions in RbCdF3: An EPR study in the cubic and tetragonal phases. PMID- 9993509 TI - Fluorescence spectra of Cr3+ dimers in LiNbO3. PMID- 9993510 TI - Two-photon spectra of single-crystal gadolinium diglycolate. PMID- 9993511 TI - Many-body energy-transfer processes between Er3+ ions in yttrium aluminum garnet. PMID- 9993512 TI - Metastable electronic populations and relaxation of Fe(I), Fe(II), and Fe(III) in MgO observed by Mossbauer emission spectroscopy. PMID- 9993513 TI - Speckle autocorrelation spectroscopy and pulse transmission as probes of photon transport in strongly scattering random media. PMID- 9993514 TI - Time-differential perturbed-angular-correlation study of 111In-111Cd in III-V compounds. PMID- 9993516 TI - Thermally generated magnetic fields in heavy-fermion superconductors. PMID- 9993515 TI - Pairing instabilities in dense hydrogen. PMID- 9993518 TI - I-V characteristics in two-dimensional frustrated Josephson-junction arrays. PMID- 9993517 TI - Thermal conductivity of single-crystal Bi-Sr-Ca-Cu-O. PMID- 9993519 TI - Universal behavior of 4He films as a function of thickness near the Kosterlitz Thouless transition. PMID- 9993520 TI - Size effects in superfluid 3He films. PMID- 9993521 TI - Unusual Seebeck and Nernst effects in the mixed state of Bi2-xPbxSr2Ca2Cu3O delta. PMID- 9993522 TI - Onset of surface superconductivity. PMID- 9993523 TI - Quantum-field-theoretical description of photoelectron emission spectra of high Tc superconductors. PMID- 9993524 TI - Optical phonons in YBa2Cu4O8 and Y2Ba4Cu7O15- delta. PMID- 9993525 TI - Renormalization from density-functional theory to strong-coupling models for electronic states in Cu-O materials. PMID- 9993526 TI - Single-ion effects in the formation of the heavy-fermion ground state in UBe13. PMID- 9993528 TI - Exactness of anyon superconductivity and its finite-temperature behavior. PMID- 9993527 TI - Approaching the metal-insulator transition. PMID- 9993529 TI - Resonating-valence-bond wave function for the two-dimensional Heisenberg model on a triangular lattice. PMID- 9993530 TI - Asymptotic limits for the penetration depth of strong-coupling superconductors. PMID- 9993531 TI - Spin and charge excitations in YBa2Cu3O7: Constraints from spin-relaxation rates in the normal state. PMID- 9993532 TI - Cu(1) and Cu(2) NMR in YBa2Cu3O7. PMID- 9993534 TI - Comparative study of final-state-interaction contributions to the dynamic response of quantum fluids. PMID- 9993533 TI - Metallization and superconducting properties of YBa2Cu3O6.2Bry. PMID- 9993535 TI - Superconductivity and oxygen ordering in (Ca,Ba,La)Cu3O7- delta. PMID- 9993536 TI - Monte Carlo study of tracer and chemical diffusion of oxygen in YBa2Cu3O6+2c. PMID- 9993537 TI - Melting of the vortex lattice in high-temperature superconductors. PMID- 9993539 TI - Deep-inelastic neutron scattering from liquid 4He. PMID- 9993538 TI - Evidence for Bose-Einstein condensation of excitons in Cu2O. PMID- 9993540 TI - Critical currents, pinning, and edge barriers in narrow YBa2Cu3O7- delta thin films. PMID- 9993541 TI - Preparation and properties of superconducting Y(Ba1-xSrx)2Cu4O8. PMID- 9993542 TI - Supercurrent tunneling between conventional and unconventional superconductors: A Ginzburg-Landau approach. PMID- 9993543 TI - Two- and three-dimensional magnetic order of the rare-earth ions in RBa2Cu4O8. PMID- 9993544 TI - Infrared studies of the superconducting energy gap and normal-state dynamics of the high-Tc superconductor YBa2Cu3O7. PMID- 9993545 TI - Model of nuclear relaxation in YBa2Cu3O7- delta. PMID- 9993546 TI - Emission of waves by moving kinks in a spatially modulated sine-Gordon system. PMID- 9993548 TI - Flux trapping in hafnium-doped Y-Ba-Cu-O ceramics: The microwave-loss-signal analysis. PMID- 9993547 TI - Dispersion relations for surface excitations as a probe for variational solutions of optimized paired-phonon analysis equations. PMID- 9993549 TI - Anisotropic pressure dependence of Tc in single-crystal YBa2Cu3O7 via thermal expansion. PMID- 9993551 TI - NMR line shapes and relaxation in incommensurate systems with a multiple-q modulation. PMID- 9993550 TI - High-temperature series for random-anisotropy magnets. PMID- 9993552 TI - Defect-induced heterogeneous transformations and thermal growth in athermal martensite. PMID- 9993553 TI - Instantons and the spectrum of Bloch electrons in a magnetic field. PMID- 9993554 TI - Wetting, surface melting, and freezing of thin films of methane adsorbed on MgO(100). PMID- 9993555 TI - Energy measurement in auxiliary-field many-electron calculations. PMID- 9993556 TI - Conductance in random inductance-capacitance networks. PMID- 9993557 TI - Theoretical evaluation of Young's moduli of polymers. PMID- 9993558 TI - Spin waves in the flux-phase description of the S=1/2 Heisenberg antiferromagnet. PMID- 9993559 TI - Three-dimensional random XY model: Application to the superfluid transition of 4He in porous media. PMID- 9993560 TI - Pair-approximation method for the quantum transverse Ising model with a random field. PMID- 9993561 TI - Ground-state phase diagrams for an oriented atomic chain on a triangular lattice. PMID- 9993563 TI - Quantized Hall effect in three dimensions. PMID- 9993562 TI - Neutron depolarization in a reentrant spin-glass system: Amorphous Fe-Mn. PMID- 9993564 TI - Optical studies of thermal cycling and hysteresis effects in elastic order disorder phase transformations. III. Alkali-metal halide cyanide double-mixed crystals. PMID- 9993565 TI - Mechanisms of phase transitions between commensurate and incommensurate phases. PMID- 9993566 TI - Additive and multiplicative perturbations on phi4 kinks. PMID- 9993567 TI - Properties of elastic percolating networks in isotropic media with arbitrary elastic constants. PMID- 9993568 TI - Quantum spin fluctuations in an itinerant antiferromagnet. PMID- 9993569 TI - Exact results for the two-dimensional Ising model in a magnetic field: Tests of finite-size scaling theory. PMID- 9993571 TI - Classical O(N) Heisenberg model: Extended high-temperature series for two, three, and four dimensions. PMID- 9993570 TI - Correlated-basis-function method for fermions on a lattice: The one-dimensional Hubbard model. PMID- 9993572 TI - Influence of contact angle on quasistatic fluid invasion of porous media. PMID- 9993574 TI - Sign reversal of the atomic scattering factor and grazing-incidence transmission at x-ray-absorption edges. PMID- 9993573 TI - Glassy dynamics of pinned charge-density waves. PMID- 9993575 TI - X-ray-absorption and Kondo problems: Variations on the Abrikosov-Migdal field theoretical renormalization-group approach. PMID- 9993576 TI - XY model with weak random anisotropy in a symmetry-breaking magnetic field. PMID- 9993577 TI - Quantum lattice fluctuations in the one-dimensional Peierls-Hubbard model. PMID- 9993578 TI - Symmetry-forbidden laser-induced voltages in YBa2Cu3O7. PMID- 9993579 TI - Intensity-dependent photon-echo relaxation in rare-earth-doped crystals. PMID- 9993580 TI - X-ray photoemission spectroscopy study of LaCuO3. PMID- 9993581 TI - Anomalous pressure dependence of optical reflectivity in the superconductor Ba0.6K0.4BiO3. PMID- 9993582 TI - Dynamics of the phase transition in proximity-effect arrays of Josephson junctions at full frustration. PMID- 9993584 TI - Conditions for the existence of a counterflow in superfluid helium. PMID- 9993583 TI - Copper-oxygen hybridization in Bi-Sr-Ca-Cu-O measured by magnetic-susceptibility anisotropy. PMID- 9993585 TI - Fluctuation effects and mass enhancement in high-Tc cuprate superconductors. PMID- 9993586 TI - Quasi-two-dimensional diffusion-limited aggregation. PMID- 9993587 TI - High-pressure phase transitions in Li2SO4. PMID- 9993589 TI - Variational approach for tunneling diffusion of a particle interacting with phonons. PMID- 9993588 TI - Hierarchical quantum Ising model. PMID- 9993590 TI - Erratum: "Collective excitations in a doped antiferromagnet" PMID- 9993592 TI - Mechanisms for annealing of ion-bombardment-induced defects on Pt(111). PMID- 9993593 TI - Nature of pairing in antiferromagnetic metals. PMID- 9993591 TI - Growth of the optical conductivity in the Cu-O planes. PMID- 9993595 TI - High-frequency flux flow in Y-Ba-Cu-O/Ag/Y-Ba-Cu-O thin-film superconducting normal-superconducting junctions. PMID- 9993594 TI - Quantum fluctuations and the onset of global superconductivity in disordered Josephson-junction arrays. PMID- 9993596 TI - H2O adsorption on Bi2Sr2CaCu2O8(001). PMID- 9993597 TI - Microwave response of YBa2Cu3O7- delta -Ag-Al-Pb superconducting proximity junctions. PMID- 9993598 TI - Anomalous Hall effect in superconductors near their critical temperatures. PMID- 9993599 TI - Giant Shapiro steps in Josephson-junction arrays. PMID- 9993600 TI - Diamagnetic response of oxide superconductors: Theoretical descriptions by the mass-reduction mechanism. PMID- 9993601 TI - Lorentz-force independence of resistance tails in magnetic fields near Tc for the low-temperature superconductor granular NbN: A Josephson-junction model. PMID- 9993602 TI - Temperature-dependent Hall coefficient of the organic super- conductor beta -di PMID- 9993603 TI - Shape of the upper-critical-field curves in URu2Si2: Evidence for anisotropic pairing. PMID- 9993604 TI - Optical pulses in tritiated solid hydrogen. PMID- 9993605 TI - Cu-O network dependence of optical charge-transfer gaps and spin-pair excitations in single-CuO2-layer compounds. PMID- 9993607 TI - Ordering of interstitial oxygen atoms in La2NiO4+ delta observed by transmission electron microscopy. PMID- 9993606 TI - Isotope effect for very large Coulomb pseudopotential. PMID- 9993608 TI - Flux-pinning mechanisms in thin films of YBa2Cu3Ox. PMID- 9993609 TI - Anomalous temperature dependence of Hall coefficients for (L2/3Ce1/3)4(La1/3Ba1/3Sr1/3)4Cu6Oy (L=Eu, Dy, Y, and Ho). PMID- 9993610 TI - Atom- and cluster-assembled interfaces: Cr growth on Bi2Sr2-xCa1+xCu2O8+y. PMID- 9993611 TI - Infrared absorptivity of YBa2Cu3O7-x crystals. PMID- 9993612 TI - Positron-annihilation studies on the YBa2Cu4O8 superconductor. PMID- 9993613 TI - Phonon Raman scattering of NbBa2Cu3Oy and Nd1.6Ba1.4Cu3Oy. PMID- 9993614 TI - Bogoliubov quasiparticles, spinons, and spin-charge decoupling in superconductors. PMID- 9993615 TI - Stability of the saturated ferromagnetic state in the one-band Hubbard model. PMID- 9993616 TI - All-electronic Peierls instability in the infinite-U mean-field theory for the Hubbard model. PMID- 9993617 TI - Phase transitions in random-anisotropy magnets. PMID- 9993618 TI - Monte Carlo renormalization-group study of the site-diluted simple-cubic Ising model. PMID- 9993619 TI - Vibrational properties of percolating clusters: Localization and density of states. PMID- 9993620 TI - Atomic motions in liquid KPb: A molecular-dynamics investigation. PMID- 9993621 TI - Pseudopotential local-spin-density studies of neutral and charged Mgn (n <= 7) clusters. PMID- 9993622 TI - L and M edges of copper: Theory and experiment. PMID- 9993624 TI - Calculations of surface core-level shifts for the lanthanides. PMID- 9993623 TI - Two-dimensional weak localization in partially graphitic carbons. PMID- 9993625 TI - Fe-Ti metastable-phase formation by ion-beam mixing. PMID- 9993626 TI - Electronic structure and magnetism of transition-metal-stabilized YFe12-xMx intermetallic compounds. PMID- 9993627 TI - Quantum diffusion of adatoms on a surface. PMID- 9993628 TI - Ionization potentials of cobalt and nickel ions in the local-spin-density approximation. PMID- 9993629 TI - Spin and orbital magnetism in 3d systems. PMID- 9993630 TI - Cohesion and lattice stabilities in the 5d transition metals: Full versus muffin tin potentials. PMID- 9993631 TI - Giant conductance fluctuations in thin metal wires. PMID- 9993633 TI - Atomistic locking and friction. PMID- 9993632 TI - First-principles study of As, Sb, and Bi electronic properties. PMID- 9993634 TI - Surface-roughness contributions to the electrical resistivity of polycrystalline metal films. PMID- 9993635 TI - Charge-density-wave conduction noise in blue bronze: Bulk-generated Gaussian noise. PMID- 9993636 TI - Angle-resolved photoemission study of relativistic effects in the bulk electronic structure of Fe. PMID- 9993638 TI - Monte Carlo simulation of the nucleation and growth of binary-alloy particles of Au, Ag, and Pd on NaCl(100) substrates. PMID- 9993637 TI - Thermal vacancies and positron-lifetime measurements in Fe76.3Al23.7. PMID- 9993639 TI - Electronic structure of ordered and disordered Cu3Au: The behavior of the Au 5d bands. PMID- 9993641 TI - Magnetic breakdown and magnetoresistance oscillations in a periodically modulated two-dimensional electron gas. PMID- 9993640 TI - Circular bends in electron waveguides. PMID- 9993642 TI - Core-hole effects in the x-ray-absorption spectra of transition-metal silicides. PMID- 9993643 TI - Electron band structure of a rare-earth metal: Tb(0001). PMID- 9993645 TI - Statistical-mechanical model in the evaluation of partial and total structure factors, atomic distribution functions, and diffusion coefficients of silver-tin liquids at various concentrations. PMID- 9993644 TI - First-principles calculation of the magnetocrystalline anisotropy energy of iron, cobalt, and nickel. PMID- 9993646 TI - Calculations on the Auger spectra of clusters modeling polymer chains. PMID- 9993647 TI - Anharmonic model for polyyne. PMID- 9993648 TI - Theory of the Hall effect in quantum wires: Effects of scattering. PMID- 9993650 TI - Eight-band k PMID- 9993649 TI - Inelastic electron scattering investigation of the Sb/GaAs(110) system. PMID- 9993652 TI - Stability and electronic properties of InAs/InP strained superlattices. PMID- 9993651 TI - Theory of dielectric-function anisotropies of (001) GaAs (2 x 1) surfaces. PMID- 9993653 TI - Experimental study of the crystal stability and equation of state of Si to 248 GPa. PMID- 9993655 TI - Shallow donors in CdTe. PMID- 9993654 TI - Growth of silicon and germanium on Cu(111) studied by angle-resolved direct and inverse photoemission. PMID- 9993656 TI - Stark shift and field-induced tunneling in AlxGa1-xAs/GaAs quantum-well structures. PMID- 9993657 TI - Hall effect near the metal-insulator transition. PMID- 9993658 TI - Development of the surface electronic structure of K and Cs overlayers on Si(111)7 x 7. PMID- 9993660 TI - Structural and electronic properties of narrow-band-gap semiconductors: InP, InAs, and InSb. PMID- 9993659 TI - Pressure dependences of the elastic constants and structural stability of Zn1 xMnxSe with x=0.37 and 0.53. PMID- 9993661 TI - Temperature dependence of the persistent photocurrent in Czochralski gallium arsenide. PMID- 9993663 TI - Localized excitons in II-VI semiconductor alloys: Density-of-states model and photoluminescence line-shape analysis. PMID- 9993662 TI - Valence-band electronic structure of NiSi2 and CoSi2: Evidence of the Si s electronic state at the Fermi edge. PMID- 9993664 TI - Electronic structure of InP/Ga0.47In0.53As interfaces. PMID- 9993665 TI - Magnetic-field effects and intrinsic bistability in resonant tunneling systems. PMID- 9993666 TI - Theory of the surface acoustic soliton. V. Approximate soliton solution of the Korteweg-de Vries type. PMID- 9993667 TI - Electron transport and impact ionization in Si. PMID- 9993668 TI - Pressure-dependent phonon properties of III-V compound semiconductors. PMID- 9993669 TI - Carrier dynamics of electrons and holes in moderately doped silicon. PMID- 9993670 TI - Defect formation in a-Si:H. PMID- 9993671 TI - Total energy, lattice dynamics, and structural phase transitions in silicon by the orthogonalized linear combination of atomic orbitals method. PMID- 9993672 TI - Electronic structure and optical absorption of ionized donor molecules in a magnetic field: A finite-element approach. PMID- 9993673 TI - Kinetics of radiative recombination in quantum wells. PMID- 9993674 TI - Interaction potential for SiO2: A molecular-dynamics study of structural correlations. PMID- 9993675 TI - Dynamics of orientational glass formation in Rb(CN)xBr1-x mixed crystals. PMID- 9993676 TI - Contributions of the electrostatic and the dispersion interaction to the solvent shift in a dye-polymer system, as investigated by hole-burning spectroscopy. PMID- 9993678 TI - Interpretation of three-photon spectra in alkali halides. PMID- 9993677 TI - Inverse-photoemission measurement of iron oxides on polycrystalline Fe. PMID- 9993679 TI - Lattice dynamics of thin layers of molecular nitrogen adsorbed on graphite. PMID- 9993680 TI - Photodarkening profiles and kinetics in chalcogenide glasses. PMID- 9993681 TI - Disorder-induced line broadening in first-order Raman scattering from graphite. PMID- 9993683 TI - Self-affine fractal dimensions of film surfaces. PMID- 9993682 TI - Ghost states for separable, norm-conserving, Iab initioP pseudopotentials. PMID- 9993685 TI - Hydrogen molecular ions in two dimensions. PMID- 9993684 TI - Praseodymium-overlayer-induced enhancement in oxide growth on aluminum and tantalum. PMID- 9993687 TI - Correlation length of a dense liquid and surface melting. PMID- 9993686 TI - Formation of artificially ordered SimSbn alloys. PMID- 9993688 TI - Erratum: Imperfections in amorphous chalcogenides. II. Detection and structure determination of neutral defects in As-S, Ge-S, and Ge-As-S glasses PMID- 9993689 TI - Elastic properties of thin fcc films. PMID- 9993690 TI - Coverage dependence of the electronic structure of chlorine adatoms on metal surfaces. PMID- 9993691 TI - Solitonlike phonon localization and two-phonon bound states of multivibrational excitations. PMID- 9993693 TI - Confirmation of the temperature-dependent photovoltaic effect on Fermi-level measurements by photoemission spectroscopy. PMID- 9993692 TI - Resonant-tunneling transfer times between asymmetric GaAs/Al0.35Ga0.65As double quantum wells. PMID- 9993694 TI - Jahn-Teller coupling at the 1.04-eV EL2-related center in GaAs. PMID- 9993695 TI - Magnetotransport through an antidot lattice in GaAs-AlxGa1-xAs heterostructures. PMID- 9993696 TI - Spin-density waves in a quasi-two-dimensional electron gas. PMID- 9993697 TI - One-dimensional subband effects in the conductance of multiple quantum wires in Si metal-oxide-semiconductor field-effect transistors. PMID- 9993699 TI - Microscopic mechanism for dopant activation in hydrogenated amorphous silicon. PMID- 9993698 TI - Induced absorption spectroscopic determination of exciton binding energies in type-II GaAs/AlAs superlattices. PMID- 9993700 TI - Numerical simulations of resonant tunneling in the presence of inelastic processes. PMID- 9993701 TI - Piezospectroscopic study of interstitial oxygen in gallium arsenide. PMID- 9993702 TI - Step-step interactions due to anisotropic surface stress. PMID- 9993703 TI - Decay times of one-dimensional excitons in GaAs/AlxGa1-xAs quantum-well wires. PMID- 9993704 TI - Cs-induced surface state on GaAs(110). PMID- 9993705 TI - Resonant magnetoconductance in a two-dimensional lateral-surface superlattice. PMID- 9993706 TI - Ballistic transport in a novel one-dimensional superlattice. PMID- 9993707 TI - Negative-charge state of hydrogen in silicon. PMID- 9993708 TI - Absolute deformation potentials in semiconductors. PMID- 9993710 TI - Polaronic satellites in x-ray-absorption spectra. PMID- 9993709 TI - Third-order nonlinear susceptibilities and polariton modes in PbTiO3 obtained by temporal measurements. PMID- 9993711 TI - O chemisorption on Cu(110) by scanning tunneling microscopy. PMID- 9993712 TI - Behavior of Ir atoms and clusters on Ir surfaces. PMID- 9993713 TI - Effective-medium calculations for hydrogen in Ni, Pd, and Pt. PMID- 9993714 TI - Influence of the valence of the substituted cations on the electrical properties of the magnetically modulated spinels Zn1-xAxCr2Se4 (A=Cu, Ga2/3). PMID- 9993715 TI - Cohesive, electronic, and structural properties of Al3Li: An important metastable phase. PMID- 9993716 TI - Edge dislocations in fcc metals: Microscopic calculations of core structure and positron states in Al and Cu. PMID- 9993717 TI - Universal scaling of nonlocal and local resistance fluctuations in small wires. PMID- 9993718 TI - Crystal structure, phase stability, and electronic structure of Ti-Al intermetallics: TiAl3. PMID- 9993719 TI - Observation of surface to bulk interatomic Auger decay from Ta(100). PMID- 9993721 TI - Linear response of general composite systems to many coupled fields. PMID- 9993720 TI - Exact Hartree-Fock exchange in one-dimensional metals. II. PMID- 9993722 TI - Photoelectron diffraction from core levels and plasmon-loss peaks of aluminum. PMID- 9993724 TI - Linear-response theory for core-hole screening in transition metals. PMID- 9993723 TI - Monte Carlo simulation applicable to the growth of rough metal overlayers: Parametric relationships related to the electrochemical roughening. PMID- 9993726 TI - Electron-positron interaction in jellium. PMID- 9993725 TI - Mossbauer and magnetic studies of Ti4+-substituted Ni-Zn ferrites. PMID- 9993727 TI - Neutron-diffraction structure in potassium near the PMID- 9993728 TI - Effect of the surface states of different transition-metal substrates on a Cs overlayer. PMID- 9993729 TI - Phase stability and electronic structure of ScAl3 and ZrAl3 and of Sc-stabilized cubic ZrAl3 precipitates. PMID- 9993731 TI - Extended phonon-scattering mechanism as an explanation for low mobility in highly concentrated electron layers at silicon interfaces. PMID- 9993730 TI - Optical response of a disordered solid with restricted size. PMID- 9993732 TI - Impurity conduction at low compensation levels in Zn-doped InP. PMID- 9993734 TI - Structural and optical properties of (100) InAs single-monolayer quantum wells in bulklike GaAs grown by molecular-beam epitaxy. PMID- 9993733 TI - Angle-resolved Auger study of 10-keV Ar+-ion-induced Si LMM atomic lines. PMID- 9993735 TI - Structure and evolution of the displacement field in hydrogen-implanted silicon. PMID- 9993736 TI - Photoemission and scanning-tunneling-microscopy study of GaSb(100). PMID- 9993737 TI - Comparative study of Si-NL8 and Si-NL10 thermal-donor-related EPR centers. PMID- 9993738 TI - Atomic and electronic structures of an interface between silicon and beta cristobalite. PMID- 9993739 TI - Donor levels and impurity-atom relaxation in nitrogen- and phosphorus-doped diamond. PMID- 9993740 TI - Energy levels of strained InxGa1-xAs-GaAs superlattices. PMID- 9993741 TI - Effect of electron-electron scattering on intervalley transition rates of photoexcited carriers in GaAs. PMID- 9993743 TI - Inter-Landau-level scattering in the valence band of zinc-blende semiconductors induced by the Frohlich interaction. PMID- 9993742 TI - Inelastic scattering of electrons by neutral impurities in semiconductors. PMID- 9993744 TI - Atomic and electronic structures of oxygen on Si(100) surfaces: Metastable adsorption sites. PMID- 9993746 TI - Pressure-driven semiconductor-metal transition in intermediate-valence TmSe1-xTex and the concept of an excitonic insulator. PMID- 9993745 TI - Observation of the fractional quantum Hall effect under hydrostatic pressure. PMID- 9993747 TI - Band offsets and interfacial properties of cubic CdS grown by molecular-beam epitaxy on CdTe(110). PMID- 9993748 TI - Theoretical studies of Si vapor-phase epitaxial growth by Iab initioP molecular orbital calculations. PMID- 9993749 TI - Effect of continuum states on two-photon absorption in quantum wells. PMID- 9993750 TI - Surface crystallography of bulk-grown CoSi2(111) by x-ray photoelectron diffraction. PMID- 9993752 TI - Molecular-dynamics determination of electronic and vibrational spectra, and equilibrium structures of small Si clusters. PMID- 9993751 TI - Light-induced change in defect-band photoluminescence of doped hydrogenated amorphous silicon. PMID- 9993754 TI - Phonon-assisted magneto-optical transitions in two-dimensional systems. PMID- 9993753 TI - Quantum Hall effect and general narrow-wire circuits. PMID- 9993755 TI - Surface geometry of (1 x 1)PHx/Ge(111) determined with angle-resolved photoemission extended fine structure. PMID- 9993756 TI - First-principles calculations of the three-dimensional structure and intrinsic defects in trans-polyacetylene. PMID- 9993757 TI - Dynamical inelastic scattering in high-energy electron diffraction and imaging: A new theoretical approach. PMID- 9993759 TI - Nonlinear optical susceptibilities of conducting polymers. PMID- 9993758 TI - Chiral Luttinger liquid and the edge excitations in the fractional quantum Hall states. PMID- 9993760 TI - Theory of magnetotransport in two-dimensional electron systems with unidirectional periodic modulation. PMID- 9993762 TI - Structure and phase transitions of grown and equilibrated alloys. PMID- 9993761 TI - Structural and vibrational properties of (Si)4/(Ge)4 superlattices. PMID- 9993764 TI - Extrinsic- and intrinsic-defect creation in amorphous SiO2. PMID- 9993763 TI - Angularly resolved light scattering from silica glass: Determination of the critical angle and scatterer density. PMID- 9993765 TI - Spectroscopic determination of the distribution of Cr3+ sites in mullite ceramics. PMID- 9993766 TI - X-ray-diffraction studies of hydration transitions in Na vermiculite. PMID- 9993767 TI - NMR study of interface structure in epitaxial Co-Cu superlattices. PMID- 9993768 TI - Rayleigh wave dispersion on Ag(100) along the <100> direction. PMID- 9993769 TI - Position of the empty surface-state band on Si(111)2 x 1. PMID- 9993770 TI - Polarizability of a carrier in an isolated well of a quantum-well wire. PMID- 9993771 TI - Modification of Stillinger-Weber potentials for Si and Ge. PMID- 9993773 TI - Magnetization of a two-dimensional electron gas. PMID- 9993772 TI - Electronic structure of alpha -Al2O3 studied by polarized x-ray-emission spectroscopy. PMID- 9993774 TI - Multicritical unbinding phenomena and nonlinear functional renormalization group. PMID- 9993775 TI - Nonlocal Wigner-like correlation-energy density functional through coordinate scaling. PMID- 9993776 TI - Relation between x-ray photoemission spectroscopy binding energies and absorption resonance energies for CO adsorbates. PMID- 9993778 TI - Effects of channel opening and disorder on the conductance of narrow wires. PMID- 9993777 TI - Observation of high-index excitonic states in AlxGa1-xAs/AlAs ternary-alloy quantum wells by two-photon spectroscopy. PMID- 9993779 TI - Near-surface GaAs/Ga0.7Al0.3As quantum wells: Interaction with the surface states. PMID- 9993780 TI - Dynamics of exciton transfer between the bound and the continuum states in GaAs AlxGa1-xAs multiple quantum wells. PMID- 9993781 TI - Local catalytic effect of cesium on the oxidation of silicon. PMID- 9993782 TI - Intersubband plasmon excitations of an electron gas in a cylindrical quantum-well wire. PMID- 9993783 TI - Iterative approaches to electronic structure with augmented bases. PMID- 9993784 TI - 4f resonances with norm-conserving pseudopotentials. PMID- 9993785 TI - Quantum-chemical molecular dynamics applied to S-P metals. PMID- 9993786 TI - de Haas-van Alphen effect in two-dimensional thin films of pure bismuth. PMID- 9993788 TI - Anisotropic diffusion at a melting surface studied with He-atom scattering. PMID- 9993787 TI - L2,3 x-ray-absorption edges of d0 compounds: K+, Ca2+, Sc3+, and Ti4+ in Oh (octahedral) symmetry. PMID- 9993789 TI - Theory of the electronic states and absorption spectrum of the LiCl:Ag+ impurity system. PMID- 9993791 TI - Electrical resistance in the c direction of graphite. PMID- 9993790 TI - Weak-localization and Coulomb-interaction effects in hydrogen-doped Zr-Ni and Zr Cu metallic glasses. PMID- 9993792 TI - Lattice dynamics of lutetium. PMID- 9993793 TI - Measurement of glasslike and crystalline elasticity in quasicrystals. PMID- 9993794 TI - Deposition of Ag ions and neutral atoms on ZnSe(100): Influence of interface morphology on Schottky-barrier formation. PMID- 9993796 TI - Excitonic effects in the optical spectrum of GaAs. PMID- 9993795 TI - Theoretical evaluation of neutron scattering intensities, partial structure factors, and diffusion coefficients of the alloy of the peculiar metal Bi in Cu Bi alloy. PMID- 9993797 TI - Influence of pair-exchange interaction on the magnetization of IV-VI-compound diluted magnetic semiconductors. PMID- 9993798 TI - Defect annealing in electron-irradiated boron-doped silicon. PMID- 9993799 TI - Annealing study of the electron-irradiation-induced defects H4 and E11 in InP: Defect transformation (H4-E11)-->H4' PMID- 9993800 TI - Atomic versus molecular reactivity at the gas-solid interface: The adsorption and reaction of atomic oxygen on the Si(100) surface. PMID- 9993801 TI - Disorder, screening, and quantum Hall oscillations. PMID- 9993802 TI - Trap-limited hydrogen diffusion in doped silicon. PMID- 9993803 TI - Role of band-tail carriers in metastable defect formation and annealing in hydrogenated amorphous silicon. PMID- 9993805 TI - Observations and calculations of the exciton binding energy in (In,Ga)As/GaAs strained-quantum-well heterostructures. PMID- 9993804 TI - Reaction and barrier formation at metal-GaP(110) interfaces. PMID- 9993806 TI - Exciton localization in InxGa1-xAs-GaAs coupled quantum-well structures. PMID- 9993808 TI - X-ray specular reflection studies of silicon coated by organic monolayers (alkylsiloxanes). PMID- 9993807 TI - High-resolution photoemission study of the interaction of hydrogen with GaAs(110) surfaces. PMID- 9993809 TI - Observation of magnetic excitons and spin waves in activation studies of a two dimensional electron gas. PMID- 9993810 TI - Magnetic-ion triplet clusters and non-nearest-neighbor exchange effect in (Cd,Mn)Te. PMID- 9993811 TI - Influences of a parallel magnetic field on localization of disordered two dimensional electrons in GaAs/AlxGa1-xAs heterostructures. PMID- 9993813 TI - Electronic structure of perovskite-type compounds. PMID- 9993812 TI - Dimensional changes of metallic glasses during bombardment with fast heavy ions. PMID- 9993814 TI - Rare-gas liquids: Equation of state and reduced-pressure, reduced-bulk-modulus, and reduced-sound-velocity functions. PMID- 9993816 TI - Hyper-Rayleigh scattering from the bulk of nominally pure KTaO3. PMID- 9993815 TI - Energy-band dispersion in oriented thin films of pentatriacontan-18-one by angle resolved photoemission with synchrotron radiation. PMID- 9993817 TI - Isotropic elasticity of the Al-Cu-Li quasicrystal. PMID- 9993818 TI - Enhancement of the van der Waals energy between an atom and a cylindrical surface: Application to the edges of stepped surfaces. PMID- 9993819 TI - Hydrogen adsorption on Si(100)-2 x 1 surfaces studied by elastic recoil detection analysis. PMID- 9993820 TI - Contribution of optical phonons to sound velocity in piezoelectric semiconductors. PMID- 9993822 TI - Erratum: Metastability of the segregation-reversal composition profile at the PtxNi1-x(110) surface: A low-energy electron-diffraction study PMID- 9993821 TI - Hot-electron spectrometry with quantum point contacts. PMID- 9993823 TI - Tip-related artifacts in scanning tunneling potentiometry. PMID- 9993824 TI - Pressure-induced stepped response in quasicrystals: Evidence for a reversible electronic transition in Al82Fe PMID- 9993825 TI - Helium release from aged palladium tritide. PMID- 9993826 TI - Inelastic photon scattering from K-shell electrons of Cu and Zr. PMID- 9993827 TI - Optimized pseudopotentials. PMID- 9993828 TI - Pressure effects on the martensitic transformation in metallic lithium. PMID- 9993830 TI - Direct characterization of charge-density-wave defects in titanium-doped TaSe2 by scanning tunneling microscopy. PMID- 9993829 TI - Role of tip electronic structure in scanning tunneling microscope images. PMID- 9993831 TI - Biexciton binding in quantum boxes. PMID- 9993833 TI - Observation of normal Hall coefficient of amorphous Si thin films prepared by low pressure chemical-vapor deposition. PMID- 9993832 TI - Generalized embedded-atom format for semiconductors. PMID- 9993835 TI - Phase transitions on the Ge(111) and Si(111) surfaces from core-level studies. PMID- 9993836 TI - Electronic states due to surface doping: Si(111) sqrt 3 x sqrt 3B. PMID- 9993834 TI - Experimental observation of attenuated-total-reflection spectra of GaAs/AlAs superlattice. PMID- 9993838 TI - Ab initio study of the geometry and electronic structure of lead iodide semiconductor clusters. PMID- 9993837 TI - Experimental photoemission results on the low-energy conduction bands of silicon. PMID- 9993839 TI - Electron-beam collimation with a quantum point contact. PMID- 9993842 TI - Subpicosecond time-resolved reflection of ultrafast electrical pulses from GaAs in the presence of nonthermal photoexcited carriers. PMID- 9993841 TI - Resonant tunneling in double-barrier heterostructures tunable by long-wavelength radiation. PMID- 9993840 TI - Observation of a Bloch-Gruneisen regime in two-dimensional electron transport. PMID- 9993843 TI - Fractional quantum Hall effect in hole Landau levels. PMID- 9993844 TI - Hole magnetoplasmons in semiconductor heterostructures. PMID- 9993845 TI - Low-frequency hydrogen-configuration fluctuations in niobium. PMID- 9993847 TI - Surface magnetism in an exactly soluble many-body periodic-cluster model of bcc iron. PMID- 9993846 TI - Characterization of a simple class of modulated relaxation oscillators. PMID- 9993848 TI - Experimental band structure of lead. PMID- 9993849 TI - Far-infrared magnetic-field-dependent resonances in small unsupported bismuth particles. PMID- 9993850 TI - Atomistic growth of two-dimensional quasicrystals. PMID- 9993851 TI - Electronic structure of impurity (oxygen)-stacking-fault complex in nickel. PMID- 9993852 TI - Magnetic field and temperature dependence of the self-trapping energy of a polaron in a polar-crystal slab in arbitrary magnetic field strength. PMID- 9993853 TI - Radiative and nonradiative recombination of bound excitons in GaP:N. I. Temperature behavior of zero-phonon line and phonon sidebands of bound excitons. PMID- 9993855 TI - Radiative and nonradiative recombination of bound excitons in GaP:N. III. Reverse tunneling of bound excitons. PMID- 9993854 TI - Radiative and nonradiative recombination of bound excitons in GaP:N. II. Nonlinear behavior of emission intensity versus excitation power of bound excitons due to exciton transfer. PMID- 9993856 TI - Airy-coordinate technique for nonequilibrium Green's-function approach to high field quantum transport. PMID- 9993857 TI - Theoretical and experimental results for p-type GaAs electrolyte electroreflectance. PMID- 9993859 TI - Additional-boundary-condition-free theory of an exciton polariton in a slab. PMID- 9993858 TI - Exciton quantization and polariton propagation in semiconductor slabs: From semi infinite crystals to quantum wells. PMID- 9993860 TI - Optical-phonon modes in a double heterostructure of polar crystals. PMID- 9993861 TI - Hyperfine interactions in the cubic semiconductor CdO. PMID- 9993862 TI - Effective bond-orbital model for shallow acceptors in GaAs-AlxGa1-xAs quantum wells and superlattices. PMID- 9993865 TI - Enhancement of the free-to-bound transition in narrow GaAs/Al0.3Ga0.7As quantum wells via a possible excitonic Auger mechanism. PMID- 9993864 TI - Frequency-dependent conductivity in bismuth-vanadate glassy semiconductors. PMID- 9993863 TI - Continuous-wave spectroscopy of femtosecond carrier scattering in GaAs. PMID- 9993866 TI - Structural and electronic properties of the liquid polyvalent elements: The group IV elements Si, Ge, Sn, and Pb. PMID- 9993867 TI - Elastic properties of trigonal laminar systems: Brillouin scattering study of Hf1 xZrxS2. PMID- 9993868 TI - Hydrogen chemisorption on Si(111)7 x 7 studied with surface-sensitive core-level spectroscopy and angle-resolved photoemission. PMID- 9993869 TI - Effects of the implantation of oxygen, nitrogen, and carbon on the density of states of n-type hydrogenated amorphous silicon. PMID- 9993870 TI - Band-structure calculation of dispersion and anisotropy in chi PMID- 9993872 TI - LO-phonon-assisted emission edge of free excitons in GaAs and GaAs/GaxAl1-xAs quantum wells. PMID- 9993871 TI - Conduction electrons in GaAs: Five-level k PMID- 9993873 TI - Electrical and dielectric properties of the Bi4Sr3Ca3Cu4Ox (4:3:3:4) glassy semiconductor. PMID- 9993875 TI - Pressure dependence of the electronic properties of cubic III-V In compounds. PMID- 9993874 TI - X-ray photoemission spectroscopy analysis of Si(111) under photocurrent-doubling conditions. PMID- 9993877 TI - Resistivity anomalies in Hg1-xFexSe for 0.55 <= T <= 100 K. PMID- 9993876 TI - Electronic and magnetic structure of 3d-transition-metal point defects in silicon calculated from first principles. PMID- 9993878 TI - Effect of disorder on the frequency-dependent dielectric constant of a composite material. PMID- 9993879 TI - Damping corrections and the calculation of optical nonlinearities in organic molecules. PMID- 9993880 TI - Phonons in solid argon monolayers. PMID- 9993881 TI - Electronic structure of polyimide and related monomers: Theory and experiment. PMID- 9993882 TI - Crystal-structure, magnetic-susceptibility, and EPR studies of bis(piperidinium)tetrabromocuprate(II): A novel monomer system showing spin diffusion. PMID- 9993883 TI - Silicon-hydrogen bond-stretching vibrations in hydrogenated amorphous silicon nitrogen alloys. PMID- 9993884 TI - Strong-coupling theory for the multidimensional free optical polaron. PMID- 9993886 TI - Enhancement in nonlinear effects in percolating nonlinear resistor networks. PMID- 9993885 TI - Effect of heating and rapidly quenching NbSe3 crystals. PMID- 9993888 TI - Thermal expansion of c-Si via ab initio molecular dynamics. PMID- 9993887 TI - Change in dimensionality of superlattice excitons induced by an electric field. PMID- 9993890 TI - Effect of a perpendicular magnetic field on small devices with crossbar geometry. PMID- 9993889 TI - Impurity states in a quantum-well wire of GaAs-Ga1-xAlxAs. PMID- 9993891 TI - Band-structure calculations of BN by the self-consistent variational cellular method. PMID- 9993893 TI - Voltage-tunable quantum dots on silicon. PMID- 9993892 TI - Highly symmetric Mn sites in icosahedral Ti-Mn. PMID- 9993894 TI - Structure of ( sqrt 3 x sqrt 3)R30 degrees Ag on Si(111). PMID- 9993895 TI - Giant diamagnetic effect in InAs electron inversion layers measured by Zener tunneling. PMID- 9993896 TI - Bremsstrahlung induced by 50-MeV H0 bombardment. PMID- 9993897 TI - Structure and magnetic properties of the (Fe2O3)-(Al2O3)x(SiO)1-x system. PMID- 9993898 TI - Short-range order in alpha -brass. PMID- 9993899 TI - Fluorescence measurements of the exciton dispersion in Gd(OH)3. PMID- 9993900 TI - Neutron scattering experiments on YbXCu4 and ErXCu4 (X=Au, Pd, and Ag). PMID- 9993901 TI - 67Zn Mossbauer investigation of lattice-dynamical effects and hyperfine interactions in ZnF2. PMID- 9993902 TI - Computer simulations on collision-cascade anisotropies: Bombardment of single crystalline Cu(100) by Ar ions. PMID- 9993903 TI - Experimental determination of a species-dependent effect in the transverse emittances of sputter-generated negative-ion beams. PMID- 9993904 TI - Observation of electron-hole cascade in photofield emission. PMID- 9993906 TI - Knight shifts and nuclear-spin-relaxation rates for two-dimensional models of CuO2. PMID- 9993905 TI - Positron-annihilation momentum density in superconductors. PMID- 9993907 TI - Impurity magnetic moments in unconventional superconductors. PMID- 9993909 TI - Theoretical investigation of intra-atomic electronic excitation energies of divalent Cu in YBa2Cu3O7-x. PMID- 9993908 TI - Thermal conductivity of condensed D-T and T2. PMID- 9993910 TI - Effect of transition-metal substitutions on competing electronic transitions in the heavy-electron compound URu2Si2. PMID- 9993911 TI - Microwave loss and oxygen annealing in YBa2Cu3Ox single crystals. PMID- 9993912 TI - Heat capacity of multilayers of 3He adsorbed on graphite at low millikelvin temperatures. PMID- 9993913 TI - Structural properties of oxygen-deficient YBa2Cu3O7- delta. PMID- 9993914 TI - Electron-phonon interaction in heavy-fermion systems. PMID- 9993915 TI - Structure of T-phase superconductors: Anomalous x-ray-diffraction study of cation ordering in LA0.9Gd0.9Sr0.2CuO4. PMID- 9993916 TI - Mechanism for heavy-fermion superconductivity. PMID- 9993917 TI - Superconducting and normal-state magnetic-susceptibility anisotropy in YBa2Cu3O7. PMID- 9993918 TI - Dislocation loops and bond-orientational order in the Abrikosov flux-line lattice. PMID- 9993919 TI - Synthesis, structure, and properties of Sr2CuO2Cl2. PMID- 9993920 TI - Antiferromagnetism in Sr2CuO2Cl2. PMID- 9993921 TI - Complex magnetic properties of the rare-earth copper oxides, R2CuO4, observed via measurements of the dc and ac magnetization, EPR, microwave magnetoabsorption, and specific heat. PMID- 9993922 TI - Numerical study of flux phases in the t-J model. PMID- 9993923 TI - Numerical simulations of long Josephson junctions driven by large external radio frequency signals. PMID- 9993924 TI - Criterion for the validity of the t-J model based upon a two-band model for copper oxides. PMID- 9993926 TI - Fluctuation effects of the superconducting order parameter in a strongly correlated system. PMID- 9993925 TI - Nonstoichiometry studies of the Y-Ba-Cu-O system in terms of a real-space scattering coherent-potential approximation. PMID- 9993927 TI - Preparation of the oxide superconductors (La,Gd,Ba,Ce)8Cu6Oz and (La,Gd,Ba,Sr,Ce)8Cu6Oz. PMID- 9993928 TI - Mobile spin bags and their interaction in the spin-density-wave background. PMID- 9993929 TI - Phonon natures in Raman spectra of Y-Ba-Cu-O compounds. PMID- 9993930 TI - Crystal structure, magnetism, and superconductivity of YBa2(Cu1-xFex)3O7+y with x=0.05-0.15. PMID- 9993932 TI - Resistivity of heavy-fermion systems in the presence of a crystalline electric field. PMID- 9993931 TI - Single-particle excitations in a quantum antiferromagnet. PMID- 9993933 TI - Oscillations of a fluxon in a finite-length ac-biased Josephson junction. PMID- 9993934 TI - Dispersive-mode theory for the high-temperature rf superconducting quantum interference device. PMID- 9993935 TI - Electron-spin-resonance determination of the internal field within the superconductor YBa2Cu3O7. PMID- 9993936 TI - Superconductivity in an oxygen hole metal. PMID- 9993937 TI - Evidence for a charge-density wave or spin-density wave in the Cu-O chains in YBa2Cu3O7-x. PMID- 9993938 TI - Lattice-dependent magnetic structure in quantum network simulations of high-Tc superconductors. PMID- 9993939 TI - Phenomenological model of the copper oxide superconductors. PMID- 9993941 TI - Dynamical information for Fe-doped YBa2Cu3O7 superconducting oxides obtained from high-temperature Mossbauer studies. PMID- 9993940 TI - Elastic constants and specific-heat measurements on single crystals of La2CuO4. PMID- 9993942 TI - Raman properties intrinsic to superconductivity in the Bi-Sr-Ca-Cu-O system. PMID- 9993943 TI - Pairing anisotropy and macroscopic anisotropy of superconductors. PMID- 9993944 TI - Microwave and ac power absorption and ac susceptibility measurements of the high Tc superconducting Tl-Ba-Ca-Cu-O system near zero field. PMID- 9993946 TI - Dynamics of sine-Gordon solitons under random perturbations: Weak additive large scale white noise. PMID- 9993945 TI - Liquid sulfur: Local-order evidence of a polymerization transition. PMID- 9993947 TI - Dynamics of sine-Gordon solitons under random perturbations: Multiplicative large scale white noise. PMID- 9993948 TI - Theoretical study of the elastic and thermodynamic properties of sodium chloride under pressure. PMID- 9993949 TI - Diffusion of noninteracting particles into a semi-infinite lattice. PMID- 9993950 TI - Two-state one-dimensional spinless Fermi gas. PMID- 9993951 TI - Transfer-matrix analysis for Ising models. PMID- 9993952 TI - Replica symmetry breaking in the spin-glass model on lattices with finite connectivity: Application to graph partitioning. PMID- 9993953 TI - Ground states of the spinless Falicov-Kimball model. PMID- 9993954 TI - Numerical study of tunneling in a dissipative system. PMID- 9993955 TI - Magnetization of a Dy(Fe11Ti) single crystal. PMID- 9993956 TI - Quantum Hall effect at finite temperatures. PMID- 9993957 TI - Precursor-mediated kinetics of domain growth. PMID- 9993958 TI - Exact enumeration of long-range-ordered dimer coverings on the square-planar lattice. PMID- 9993959 TI - Heisenberg model for the square-planar lattice and fragments. PMID- 9993960 TI - Structure function of linear polymers in a good solvent: A self-avoiding-walk model. PMID- 9993961 TI - Nonequilibrium entropy and entropy distributions. PMID- 9993963 TI - Simulation of solitons in an Ising-like S=(1/2 antiferromagnet on a linear chain. PMID- 9993962 TI - Atomic mobility in Cahn's diffusion model. PMID- 9993964 TI - Mode locking and spatiotemporal chaos in periodically driven Gunn diodes. PMID- 9993965 TI - Magnetic and transport properties of (La,Ce)Ni2. PMID- 9993966 TI - Numerical study of the two-dimensional Hubbard model for various band fillings. PMID- 9993968 TI - Bethe-ansatz wave function, momentum distribution, and spin correlation in the one-dimensional strongly correlated Hubbard model. PMID- 9993967 TI - Continuous-space Monte Carlo study of a generalized lattice-gas model. PMID- 9993969 TI - Some properties of the surface magnetization of bulk magnets. PMID- 9993971 TI - Molecular-dynamics computer simulation applied to nonphotochemical hole-burning processes: Resorufin in glycerol. PMID- 9993970 TI - Phenomenological model for the phase-transition sequence in betaine calcium chloride dihydrate. PMID- 9993973 TI - Model for the linear- and nonlinear-optical properties of beta -quinol clathrates. PMID- 9993972 TI - Magnetic susceptibilities of rare-earth ions in an unusual tetrahedral site. PMID- 9993974 TI - Instability of the Nagaoka ferromagnetic state of the U= PMID- 9993975 TI - Maximum-entropy method for analytic continuation of quantum Monte Carlo data. PMID- 9993976 TI - Measurement of defect mobility in a defect-mediated melting. PMID- 9993977 TI - Low-frequency relaxation modes and structural disorder in KTa1-xNbxO3. PMID- 9993978 TI - Relaxation behavior in atomic and molecular glasses. PMID- 9993979 TI - First-principles Fourier approach for the calculation of the effective dielectric constant of periodic composites. PMID- 9993981 TI - Shape fluctuations of crystal bars. PMID- 9993980 TI - Density-functional approach to doped magnetic semiconductors: Evolution of bound states of electrons as the donor concentration increases. PMID- 9993982 TI - Transport in networks with a power-law distribution of conductances: The ladder and the Sierpinski gasket. PMID- 9993983 TI - First-order phase transition induced by quantum fluctuations in Heisenberg helimagnets. PMID- 9993984 TI - Quantum-interference magnetoconductivity in the variable-range-hopping regime. PMID- 9993985 TI - Thermodynamic behavior of a Penrose-tiling quasicrystal. PMID- 9993986 TI - Phase transitions of quasi-two-dimensional antiferroelectric squaric acid (H2C4O4) and (D2C4O4) investigated by the Green's-function technique. PMID- 9993987 TI - Quantum Monte Carlo study of the one-dimensional symmetric Anderson lattice. PMID- 9993988 TI - Fully frustrated fractal. PMID- 9993989 TI - Spin correlations in the two-dimensional S=1 Heisenberg antiferromagnet. PMID- 9993990 TI - Superconductivity and its pressure dependence in the Pb-doped Tl-Ba-Ca-Cu-O superconductors. PMID- 9993991 TI - Anisotropic thermal conductivity of superconducting lanthanum cuprate. PMID- 9993992 TI - Van Hove correlation functions for identical fermions: Effects of interactions. PMID- 9993993 TI - Variable normal-state transport properties of Bi2Sr2CaCu2O8-y. PMID- 9993994 TI - Electron-hole liquid model for high-Tc superconductors. PMID- 9993995 TI - n=(1/4 domain-growth universality class: Crossover to the n=(1/2 class. PMID- 9993996 TI - Linear spin waves in a frustrated Heisenberg model. PMID- 9993997 TI - Coexistence of spiral spin-density waves and superconductivity: Ground-state properties. PMID- 9993998 TI - Landau theory of the magnetic phase diagram of CsMnBr3. PMID- 9993999 TI - Phase boundary of the two-dimensional Ising model with ferromagnetic and antiferromagnetic interactions in a magnetic field. PMID- 9994000 TI - Induced anisotropy in reentrant Ni77Mn23 studied by transverse ac susceptibility. PMID- 9994001 TI - Late-stage two-dimensional coarsening of circular clusters. PMID- 9994002 TI - Infinite Ud,Up ground state of the extended Hubbard model. PMID- 9994003 TI - Reply to "Infinite Ud, Up ground state of the extended Hubbard model" PMID- 9994005 TI - Reply to "Comment on 't/U expansion for the Hubbard model"' PMID- 9994004 TI - Comment on "t/U expansion for the Hubbard model" PMID- 9994006 TI - Magnetic ordering of Nd in (Nd,Ce)2CuO4. PMID- 9994007 TI - Crossover in the vibrational density of states of silica aerogels studied by high resolution neutron spectroscopy. PMID- 9994009 TI - Hole excitation spectra in cuprate superconductors: A comparative study of single and multiple-band strong-coupling theories. PMID- 9994008 TI - Effect of paramagnetic percolation on Gd3+ EPR linewidths in LiYbxY1-xF4 single crystals. PMID- 9994010 TI - Dynamics of one hole in the t-J model. PMID- 9994012 TI - Little-Parks oscillations of Tc in patterned microstructures of the oxide superconductor YBa2Cu3O7: Experimental limits on fractional-statistics-particle theories. PMID- 9994011 TI - Magnetic, thermal, and transport properties of UIr2Si2. PMID- 9994014 TI - Superfluid phase slippage in 3He flow through a narrow channel. PMID- 9994013 TI - Transient-hole burning in the infrared spectrum of a polymer with intense picosecond pulses. PMID- 9994015 TI - Magnetism and superconductivity in doped La2CuO4. PMID- 9994016 TI - Density and symmetry of unoccupied electronic states of Tl2Ba2CaCu2O8. PMID- 9994017 TI - Fluctuations in an impure unconventional superconductor. PMID- 9994018 TI - Superfluxons in periodically inhomogeneous long Josephson junctions. PMID- 9994020 TI - Superconductivity and thermoelectric power of Pr1.85Ce0.15CuO4-y. PMID- 9994019 TI - Effect of fractons in strongly coupled superconductors. PMID- 9994021 TI - Dimensionality of localization in nonsuperconducting Bi2+xSr2-yCuO6+ delta crystals. PMID- 9994023 TI - Time-reversed memory effects. PMID- 9994022 TI - Magnetic phase transition in a two-dimensional system: p(1 x 1)-Ni on Cu(111). PMID- 9994024 TI - Spectral function of the Anderson model: A quantum Monte Carlo calculation. PMID- 9994025 TI - Magnetic surface states on Fe(001). PMID- 9994026 TI - Perturbative and variational calculations of charge fluctuations of an extended Hubbard model. PMID- 9994027 TI - Improved form of static scaling for the nonlinear magnetization in spin glasses. PMID- 9994028 TI - Mean-field theory of the spiral phases of a doped antiferromagnet. PMID- 9994029 TI - Elastic anomalies at the charge- and spin-density-wave transition. PMID- 9994030 TI - Ginzburg-Landau theory of diamagnetic phase transitions in a quasi-two dimensional electron gas. PMID- 9994031 TI - Resonant-tunneling theory of imaging close-packed metal surfaces by scanning tunneling microscopy. PMID- 9994033 TI - Validity and accuracy of multiple-scattering theory. PMID- 9994032 TI - Atomic displacements during structural relaxation in a metallic glass. PMID- 9994034 TI - Electron transmission through a dirty surface in low-energy spectroscopy experiments. PMID- 9994035 TI - Absence of volume metastability in bcc copper. PMID- 9994036 TI - Phonon-assisted energy-transfer process in a bottlenecked lattice. PMID- 9994037 TI - Effect of interatomic potential on simulated grain-boundary and bulk diffusion: A molecular-dynamics study. PMID- 9994038 TI - NMR studies of NbSe3: Electronic structures, static charge-density-wave measurements, and observations of the moving charge-density wave. PMID- 9994040 TI - Edge melting of tetramethyltin submonolayers physisorbed on graphite basal planes. PMID- 9994039 TI - Stability of monatomic and diatomic quasicrystals and the influence of noise. PMID- 9994041 TI - Electronic structure of Z+1 impurities in metals. PMID- 9994042 TI - Observation of anomalously increasing phonon damping constant in the beta phase of the fast-ionic conductor Ag3SI. PMID- 9994043 TI - Tip-sample interaction effects in scanning-tunneling and atomic-force microscopy. PMID- 9994044 TI - Electrical resistivity of liquid nickel-lanthanum and nickel-cerium alloys. PMID- 9994045 TI - Diffusion in concentrated lattice gases: Intermediate incoherent dynamical scattering function for tagged particles on a square lattice. PMID- 9994046 TI - Theory of phase conjugation of light in disordered nonlinear media. PMID- 9994047 TI - Dynamic-coupling model: Interpretation of temperature-, dopant-concentration-, and coverage-dependent Schottky-barrier formation. PMID- 9994048 TI - Self-consistent dipole theory of heterojunction band offsets. PMID- 9994049 TI - Interface-bond-polarity model for semiconductor heterojunction band offsets. PMID- 9994050 TI - Band bending in the initial stages of Schottky-barrier formation for gallium on Si(113). PMID- 9994051 TI - Indirect tunneling in a short GaAs-AlAs superlattice detected by photoluminescence under hydrostatic pressure. PMID- 9994052 TI - Photoluminescence decay times of the defect-induced bound-exciton lines in GaAs grown by molecular-beam epitaxy. PMID- 9994053 TI - Exciton states in type-I and type-II GaAs/Ga1-xAlxAs superlattices. PMID- 9994054 TI - Ultrafast recombination and trapping in amorphous silicon. PMID- 9994055 TI - Line-shape analysis of the reflectivity spectra of GaAs/(Ga,Al)As single quantum wells grown on (001)- and (311)-oriented substrates. PMID- 9994056 TI - Optical studies of electric field domains in GaAs-AlxGa1-xAs superlattices. PMID- 9994057 TI - Stark shifts in GaAs-Ga1-xAlxAs finite-length superlattices. PMID- 9994058 TI - Effects of the localized state inside the barrier on resonant tunneling in double barrier quantum wells. PMID- 9994059 TI - Hole transport theory in pseudomorphic Si1-xGex alloys grown on Si(001) substrates. PMID- 9994060 TI - Transport characteristics of series ballistic point contacts. PMID- 9994061 TI - Radiative and nonradiative recombination of bound excitons in GaP:N. IV. Formation of phonon sidebands of bound excitons. PMID- 9994062 TI - Photoreflectance study on residual strain in heteroepitaxial gallium arsenide on silicon. PMID- 9994063 TI - Near-infrared free-carrier optical absorption in silicon: Effect of first-order phonon-assisted scattering in a nonparabolic conduction band. PMID- 9994064 TI - Electronic-structure study of the (110) inversion domain boundary in SiC. PMID- 9994065 TI - E2 interband transitions in AlxGa1-xAs alloys. PMID- 9994066 TI - Memory-function analysis of ac transport in a tunneling superlattice. PMID- 9994067 TI - X-ray structure of Cs-doped polyacetylene. PMID- 9994068 TI - Modification of heterojunction band offsets by thin layers at interfaces: Role of the interface dipole. PMID- 9994071 TI - Electronic and chemical properties of In and Sb adsorbed on Ge(100) studied by synchrotron photoemission. PMID- 9994070 TI - Step-height-tripling transition on vicinal Si(111). PMID- 9994069 TI - Photoemission from the (001) surface of 1T-TiSe2: Comparison of calculation with experiment. PMID- 9994073 TI - Theory of one-phonon resonant Raman scattering in a magnetic field. PMID- 9994072 TI - Temperature-dependent exciton linewidths in semiconductor quantum wells. PMID- 9994074 TI - Resonant magneto-Raman scattering in GaAs. PMID- 9994075 TI - Comparison of electron bands of hexagonal and cubic diamond. PMID- 9994076 TI - Resonant tunneling through Landau levels in quantum wells in the presence of inelastic-scattering broadening. PMID- 9994077 TI - Temperature-dependent resistivity of heavily doped silicon and germanium. PMID- 9994078 TI - Synchrotron-radiation study of Fe 3d states in Cd1-xFexSe (0 <= x <= 0.4). PMID- 9994079 TI - Piezospectroscopic evidence for tetrahedral symmetry of the EL2 defect in GaAs. PMID- 9994080 TI - Impact ionization of free excitons in stressed pure germanium. PMID- 9994081 TI - Exact time-domain description of the crossover from random to Coulomb-regulated single-electron tunneling in ultrasmall normal tunnel junctions. PMID- 9994082 TI - Auger and electron-energy-loss spectroscopy study of interface formation in the Ti-Si system. PMID- 9994083 TI - Absorption and refraction spectroscopy of a tunable-electron-density quantum-well and reservoir structure. PMID- 9994085 TI - Temperature dependence of the cyclotron resonance linewidth in a GaAs/AlxGa1-xAs heterostructure. PMID- 9994084 TI - Hall effect in narrow channels. PMID- 9994086 TI - Magnetoplasmon excitations in a periodically modulated two-dimensional electron gas. PMID- 9994087 TI - Gamma -X mixing effect in GaAs/AlAs superlattices and heterojunctions. PMID- 9994088 TI - Valence photoelectron spectroscopy of Gd silicides. PMID- 9994089 TI - Anderson localization of the exciton-polariton in doped semiconductors. PMID- 9994090 TI - Nature of energy transfer processes in F-center-CN--defect pairs in CsCl. PMID- 9994091 TI - Effective image potential and surface electronic states outside stepped dielectric surfaces. PMID- 9994092 TI - Temperature and frequency dependence of the sound velocity in vitreous silica due to scattering off localized modes. PMID- 9994093 TI - Polymorphism and the glasslike state of cyanide mixed crystals: A mesoscopic problem. PMID- 9994094 TI - Effect of Cu alloying on metastable photoinduced absorption in Cux(As0.4Se0.6)1-x and Cux(As0.4S0.6)1-x glasses. PMID- 9994095 TI - Surface adsorption: Quantum reflection versus polaron collapse. PMID- 9994097 TI - Electronic structure of Ag2O. PMID- 9994096 TI - Temperature dependence of Debye-Waller factor in dye-doped polymers. PMID- 9994098 TI - Formation of hydrogenated amorphous carbon films of controlled hardness from a methane plasma. PMID- 9994099 TI - Electronic structure of vacancy defects in MgO crystals. PMID- 9994100 TI - GaAs(111)A-(2 x 2) reconstruction studied by scanning tunneling microscopy. PMID- 9994101 TI - Fast iterative diagonalization of nonlocal pseudopotential Hamiltonians using the fast Fourier transformation. PMID- 9994102 TI - Three-particle forces in hexagonal-close-packed Ho. PMID- 9994103 TI - Determination of energy spectrum parameters for two-dimensional carriers from the quantum oscillation beating pattern. PMID- 9994104 TI - Theory of excitons in short-period superlattices. PMID- 9994105 TI - Elementary integral of Bessel functions. PMID- 9994107 TI - Comment on "Stress field in quantum systems" PMID- 9994106 TI - Reply to "Elementary integral of Bessel functions" PMID- 9994108 TI - Erratum: Stretched-exponential law for carrier capture kinetics of a trapping center in compensated amorphous silicon PMID- 9994110 TI - Ballistic electronic conductance of a wide orifice. PMID- 9994109 TI - Effect of pressure on the high-magnetic-field electronic phase transition in graphite. PMID- 9994111 TI - Limitations of the universal embedding functions in the embedded-atom method. PMID- 9994112 TI - Liquid arsenic: Comparison of ab initio and pair-potential predictions of molecular structure. PMID- 9994113 TI - Differential absorption spectroscopy of charge distributions in double-barrier tunnel structures. PMID- 9994114 TI - Coupling of plasma modes in a Si accumulation layer. PMID- 9994115 TI - Biexciton-biexciton and exciton-electron scattering in GaAs quantum wells. PMID- 9994116 TI - Atomic structure of Si(111) ( sqrt 3-bar x sqrt 3-bar)R30 degrees-B by dynamical low-energy electron diffraction. PMID- 9994117 TI - New type of optical bistability in polymers mediated by phonons. PMID- 9994118 TI - Static charge fluctuations in Ga+-implanted silicon. PMID- 9994119 TI - Quantum corrections to conductivity observed at intermediate magnetic fields in a high-mobility GaAs/AlxGa1-xAs two-dimensional electron gas. PMID- 9994121 TI - Theory of spin-polarized metastable-atom-deexcitation spectroscopy: Ni-He. PMID- 9994120 TI - Dielectric function of CaF2 between 10 and 35 eV. PMID- 9994123 TI - Experimental equations of state for calcium, strontium, and barium metals to 20 kbar from 4 to 295 K. PMID- 9994122 TI - Development of an embedded-atom potential for a bcc metal: Vanadium. PMID- 9994124 TI - Electrostriction in the semiconductor-to-metal transition of liquid Se-Te alloys. PMID- 9994125 TI - Longitudinal-optical-vibration-induced high transparency of nominally opaque thin films. PMID- 9994126 TI - Growth of Rh, Pd, and Pt films on Cu(100). PMID- 9994128 TI - Electronic properties of ultrathin nickel films on W(110). PMID- 9994127 TI - Transient nonlinear optical response of strongly coupled localized electron phonon systems. PMID- 9994129 TI - Bond-orbital theory of linear and nonlinear electronic response in ionic crystals. I. Linear response. PMID- 9994130 TI - Bond-orbital theory of linear and nonlinear electronic response in ionic crystals. II. Nonlinear response. PMID- 9994131 TI - Static energetics of metallic-monolayer-on-metal structures. PMID- 9994132 TI - Strong anisotropy in the Rayleigh phonon dispersion relation on Pt(111) induced by a p(2 PMID- 9994133 TI - Six-dimensional crystal related to T2-phase Al6CuLi3 icosahedral quasicrystal and R-phase Al5CuLi3 body-centered-cubic crystal. PMID- 9994134 TI - Hydrogen adsorption on the beta -N-covered W(100) surface: An infrared study of the W-H stretch. PMID- 9994135 TI - Growth mode and magnetic behavior of thin Fe films on Cu3Au(001) studied by low energy electron diffraction and spin-resolved electron spectroscopies. PMID- 9994136 TI - Multipole response of metal spheres to q-dependent excitation operators. PMID- 9994138 TI - Generalized Lyddane-Sachs-Teller relation and disordered solids. PMID- 9994137 TI - Core-level photoemission from alkali metals on Ru(001). PMID- 9994139 TI - Hydrogen vibrational modes and anisotropic potential in alpha -ScHx. PMID- 9994141 TI - Boson enhancement of finite-temperature coherent dynamics for deuterium in metals. PMID- 9994140 TI - Experimental observation of interfacial slippage at the boundary of molecularly thin films with gold substrates. PMID- 9994142 TI - Transformation of the two-dimensional decagonal quasicrystal to one-dimensional quasicrystals: A phason strain analysis. PMID- 9994143 TI - Electric polarizability of small metal particles. PMID- 9994145 TI - Effects of the indirect transitions on optical dispersion relations. PMID- 9994144 TI - Intracollisional field effect in the high-field regime of the quantum transport equation using Monte Carlo simulations. PMID- 9994146 TI - Huge electric fields in Ge/GaAs (001) and (111) superlattices and their effect on interfacial stability. PMID- 9994147 TI - Resonance of the one-dimensional electron transmission above a quantum well with dissipation. PMID- 9994148 TI - Optical Stark effect of the exciton. II. Polarization effects and exciton splitting. PMID- 9994149 TI - Optical properties of highly oriented fibrous polyacetylene. PMID- 9994150 TI - Theoretical investigation of graphitic BeO. PMID- 9994151 TI - Electronic spectra of crystals with a subzone resummation technique. PMID- 9994152 TI - Theory of interband Auger recombination in semiconductors. PMID- 9994153 TI - Many-body theory of energy relaxation in an excited-electron gas via optical phonon emission. PMID- 9994154 TI - Anisotropic polarons near interfaces of polar semiconductors. PMID- 9994155 TI - Phonons in a surface with a mass defect: As:Si(111)(1 x 1). PMID- 9994156 TI - Alloy disorder effects on the electronic properties of III-V quaternary semiconductor alloys. PMID- 9994157 TI - Metal-adsorbate-induced Si(111)-(1 x 3) reconstruction. PMID- 9994158 TI - Elastic-scattering effects on resonant tunneling in double-barrier quantum-well structures. PMID- 9994159 TI - Enhanced plasmon anomaly in the dynamical conductivity of heterostructures with large spacer. PMID- 9994160 TI - Self-energy correction for the energy bands of silicon by the full-potential linearized augmented-plane-wave method: Effect of the valence-band polarization. PMID- 9994161 TI - Ultrashort solitons in coupled electron-phonon systems. PMID- 9994162 TI - Experimental study of the expansion mechanism of the solid-state plasma in silicon. PMID- 9994164 TI - Thermal instability of the trans-polyacetylene polaron. PMID- 9994163 TI - Electronic structure of GaAs/AlAs symmetric superlattices: A high-pressure study near the type-I-type-II crossover. PMID- 9994165 TI - Inelastic scattering in a doped polar semiconductor. PMID- 9994166 TI - Electronic and optical properties of III-V and II-VI semiconductor superlattices. PMID- 9994167 TI - Small-crystal approach to ordered semiconductor compounds. PMID- 9994168 TI - Molecular-dynamics simulation of amorphous and epitaxial Si film growth on Si(111). PMID- 9994169 TI - Intersubband carrier relaxation in highly excited GaAs/Ga1-xAlxAs multiple quantum wells. PMID- 9994170 TI - Effect of biaxial strain on acceptor-level energies in InyGa1-yAs/AlxGa1-xAs (on GaAs) quantum wells. PMID- 9994171 TI - Computer models for amorphous silicon hydrides. PMID- 9994172 TI - Structural models for alkali-metal complexes of polyacetylene. PMID- 9994174 TI - Surface electronic structure of heavily-ion-implanted and laser-annealed Si single crystals. PMID- 9994173 TI - Acceptor-related photoluminescence study in GaAs/Ga1-xAlxAs quantum wells. PMID- 9994175 TI - Magnetospectral analysis of tunneling processes in a double-quantum-well tunneling structure. PMID- 9994177 TI - Characterization of Raman scattering spectra in ternary compound semiconductors. PMID- 9994176 TI - Analysis of the composite structures in diamond thin films by Raman spectroscopy. PMID- 9994178 TI - Off-equilibrium population of holes in the stress-split valence bands in photoexcited silicon and germanium. PMID- 9994180 TI - Influence of alloy disorder on the vibrational properties of Si/Ge superlattices. PMID- 9994179 TI - Electrical and thermal properties of neutron-transmutation-doped Ge at 20 mK. PMID- 9994181 TI - Low-frequency dynamics in superionic borate glasses by coupled Raman and inelastic neutron scattering. PMID- 9994182 TI - Oxygen-isotope exchange between CO adsorbate and MgO surfaces. PMID- 9994183 TI - Luminescence and defect formation in undensified and densified amorphous SiO2. PMID- 9994184 TI - Simulation of ionic crystals: The ab initio perturbed-ion method and application to alkali hydrides and halides. PMID- 9994185 TI - Computer modeling and Brillouin scattering studies of anharmonicity and high temperature disorder in LaF3. PMID- 9994186 TI - Vibrational properties of Bi2CuO4. PMID- 9994188 TI - Thermal and optical properties of the FA and (F2+)A centers in Na-doped CaF2 crystals. PMID- 9994187 TI - Low-frequency dispersion of the dielectric permittivity in a triglycine sulfate crystal subjected to nonequilibrium conditions. PMID- 9994189 TI - Observation of the effect of tip electronic states on tunnel spectra acquired with the scanning tunneling microscope. PMID- 9994191 TI - Surface core-level shifts of InAs(110). PMID- 9994190 TI - Magnetoresistance due to enhanced electron-electron interactions in amorphous Ca70(Mg,Al)30. PMID- 9994192 TI - Depolarization shift in a double-layered lateral multiwire superlattice. PMID- 9994193 TI - Surface core-level shift of lead sulfide. PMID- 9994194 TI - Elastic scattering from cubic lattice systems with paracrystalline distortion. II. PMID- 9994196 TI - Reply to "Comment on 'Existence of Wannier-Stark localization' " PMID- 9994195 TI - Comment on "Existence of Wannier-Stark localization" PMID- 9994197 TI - Near-edge x-ray-absorption fine-structure spectroscopy measurement of the p symmetry unoccupied states of silver, palladium, and palladium silicide. PMID- 9994198 TI - Electronic and magnetic coupling between rare-earth adatoms and the Fe(001) surface. PMID- 9994199 TI - Phonon spectra of ultrathin GaAs/AlAs superlattices: An ab initio calculation. PMID- 9994200 TI - Theory of nonlinear transport in narrow ballistic constrictions. PMID- 9994201 TI - Comparative photoemission study of low-pressure hydrogen, silane, and disilane adsorption on Si(111)7 x 7. PMID- 9994202 TI - Microscopic structure of hydrogen-shallow-donor complexes in crystalline silicon. PMID- 9994203 TI - Microscopic structure of the hydrogen-phosphorus complex in crystalline silicon. PMID- 9994205 TI - Systematic approach to developing empirical potentials for compound semiconductors. PMID- 9994206 TI - Fourier-transform and continuous-wave EPR studies of nickel in synthetic diamond: Site and spin multiplicity. PMID- 9994204 TI - Temperature dependence of compositional disordering of GaAs-AlAs superlattices during MeV Kr irradiation. PMID- 9994207 TI - 2D NMR and 35Cl nuclear-quadrupole-resonance study of ammonium-ion motion and phase transitions in natural and deuterated (NH4)2TeCl6. PMID- 9994208 TI - Stress model for the wrinkling of ion-implanted layers. PMID- 9994210 TI - Theoretical study of the application of positron-induced Auger-electron spectroscopy. PMID- 9994209 TI - Experimental verification of the stress model for the wrinkling of ion-implanted layers. PMID- 9994211 TI - Effects of positron spin polarization on orthopositronium and parapositronium formation in a magnetic field. PMID- 9994212 TI - Experimental study of point-defect creation in high-energy heavy-ion tracks. PMID- 9994213 TI - Stopping powers and energy loss of Mylar, Kapton, Havar, and Ni for 10 Z=3-17 ions in the energy range 0.2-2.1 MeV/amu. PMID- 9994214 TI - Experimental study of molecular and cluster effects in secondary electron emission. PMID- 9994216 TI - Computer simulations of radiation damage in amorphous solids. PMID- 9994215 TI - Defects in ion-implanted uranium nitride. PMID- 9994217 TI - Absence of localization in energy space of a Bloch electron driven by a constant electric force. PMID- 9994219 TI - Phase transitions in dissipative Josephson chains. PMID- 9994218 TI - Thermopower of RBa2Cu3O7-x (R=Y,Er). PMID- 9994221 TI - Correlations and insulating state in La2CuO4. PMID- 9994220 TI - Andreev scattering in anisotropic superconductors. PMID- 9994222 TI - Superconducting transport properties of grain boundaries in YBa2Cu3O7 bicrystals. PMID- 9994224 TI - Far-infrared absorptivity of superconducting Pb-Bi alloys. PMID- 9994223 TI - Valence-electron states of YBa2Cu3O7- delta characterized by combined x-ray and photoemission studies. PMID- 9994225 TI - Phase separation in a high-pressure-oxygenated La2CuO4+ delta crystal: Evidence from anisotropic electronic transport and magnetic susceptibility. PMID- 9994227 TI - Analysis of the proximity-induced Josephson effect in superconducting-normal contacts. PMID- 9994226 TI - BaBiO3 and the effect of potassium substitution using photoemission. PMID- 9994229 TI - Critical fluctuations in superconductors. PMID- 9994228 TI - Electron-spectroscopy study of YbXCu4 (X=Ag,Au,Pd). PMID- 9994230 TI - Superposition of decaying flux distributions: A memory effect from flux creep. PMID- 9994231 TI - Direct observation of discommensurate walls in Bi-Ca-Sr-Cu-O superconductors. PMID- 9994232 TI - Magnetic order of the Cu planes and chains in RBa2Cu3O6+x. PMID- 9994233 TI - Substitution of 3d metals for Cu in Bi2(Sr0.6Ca0.4)3Cu2Oy. PMID- 9994235 TI - Thermoelectric power of YBa2Cu3O7- delta. PMID- 9994234 TI - Calcium-substituted Y-Ba-Cu-O superconductors with enhanced Tc synthesized at elevated oxygen pressures. PMID- 9994236 TI - Structural phase diagram of the Ba1-xKxBiO3 system. PMID- 9994238 TI - One-dimensional narrow-band model for heavy fermions and resonating valence bonds. PMID- 9994237 TI - Resonant quasiparticle-ion scattering in anisotropic superfluid 3He. PMID- 9994239 TI - Structural and superconducting properties of oxygen-deficient NdBa2Cu3O7- delta. PMID- 9994240 TI - Perturbed period-doubling bifurcation. I. Theory. PMID- 9994241 TI - Perturbed period-doubling bifurcation. II. Experiments on Josephson junctions. PMID- 9994242 TI - Electron-energy-loss spectroscopy of YBa2Cu3-xFexO7-y superconductors. PMID- 9994243 TI - O 2p holes: Temperature effects and surface characteristics of cuprate superconductors. PMID- 9994244 TI - Symmetries of the superconducting order parameters in the doped spin-liquid state. PMID- 9994245 TI - X-ray-diffraction study of a thermomechanically detwinned single crystal of YBa2Cu3O6+x. PMID- 9994246 TI - Temperature dependence of the phonon and roton excitations in liquid 4He. PMID- 9994247 TI - Interaction of dislocations with a local defect in an atomic chain with a nonconvex interparticle potential. PMID- 9994248 TI - Analysis of the linear response of quantum liquids in the near-asymptotic region. PMID- 9994249 TI - Soft-x-ray emission spectroscopy study of La2CuO4 and three high-Tc superconductors. PMID- 9994250 TI - Upward curvature of Hc2 in high-Tc superconductors: Possible evidence for s-d pairing. PMID- 9994251 TI - Major normal and superconducting parameters of high-Tc oxides. PMID- 9994252 TI - Flux creep and penetration in Fe-doped YBa2Cu3O7. PMID- 9994253 TI - Specific-heat anomaly near Tc of the (Bi,Pb)-Sr-Ca-Cu-O superconductor (Tc=107 K). PMID- 9994254 TI - Oxidation thermodynamics of YBa2Cu3O6+y: Evidence for the presence of localized oxygen p holes. PMID- 9994255 TI - New high-pressure phase of ZrO2 above 35 GPa. PMID- 9994256 TI - Dynamical properties of two-dimensional quasicrystals. PMID- 9994257 TI - Electrical conduction in checkerboard geometries. PMID- 9994258 TI - Landau-Ginzburg model of interphase boundaries in improper ferroelastic Perovskites of D4h18 symmetry. PMID- 9994259 TI - Contribution to the theory of melting. PMID- 9994260 TI - Neutron-diffraction study of the pressure-temperature phase diagram of EuAs3. PMID- 9994261 TI - Melting and orientational epitaxy in argon and xenon monolayers on graphite. PMID- 9994262 TI - New formalism for the study of lattice Hamiltonians. PMID- 9994263 TI - New percolation structures in dilute antiferromagnetic Potts models. PMID- 9994264 TI - Critical dynamics near a surface structural phase transition. PMID- 9994265 TI - Study of the accuracy of the Gutzwiller wave function for the two-dimensional Hubbard model. PMID- 9994266 TI - Scaling analysis of the new multicritical behavior of CsMnBr3 and CsNiCl3. PMID- 9994267 TI - Phase transitions in surface segregation of PtcNi1-c alloys from tight-binding Ising-model calculations. PMID- 9994268 TI - Crystallinity in liquid films. PMID- 9994269 TI - Mesoscopic rings driven by time-dependent magnetic flux: Level correlations and localization in energy space. PMID- 9994270 TI - Superconductivity, hole motion, and spin-charge correlations in the t-J model in two dimensions. PMID- 9994271 TI - Approach to equilibrium of a spin-glass. PMID- 9994272 TI - Formulas for the Chadi-Cohen process. PMID- 9994273 TI - First- and second-order transitions in the quantum hard-rod system by Monte Carlo simulation. PMID- 9994274 TI - Anisotropic second-order nonlinearities of organic monolayers. PMID- 9994275 TI - Asymptotic limit for Hc2 in Eliashberg theory. PMID- 9994277 TI - Large-N limit of the square-lattice t-J model at (1/4 and other filling fractions. PMID- 9994276 TI - Structure and magnetism of Bi2(Sr,Ca)2MnO6+y antiferromagnets with ferrimagnetic layers. PMID- 9994278 TI - Effective-medium theory of sedimentary rocks. PMID- 9994279 TI - Magneto-optical effects of excitons in BiI3 crystals under pulsed high magnetic fields: Indirect and direct excitons. PMID- 9994280 TI - Equilibrium quasicrystal phase of a Penrose tiling model. PMID- 9994282 TI - Ground-state correlations of quantum antiferromagnets: A Green-function Monte Carlo study. PMID- 9994281 TI - Gutzwiller-type approach of the size-dependent valence change in small Pr aggregates. PMID- 9994284 TI - Rotational magnetic properties of Ni-Mn and Au-Fe spin-glass alloys. PMID- 9994283 TI - Effect of lattice discreteness on the statistical mechanics of a dilute gas of kinks. PMID- 9994285 TI - Spin-glass ordering in three-dimensional Heisenberg systems. PMID- 9994286 TI - Interfacial profiles in the rough phase. PMID- 9994288 TI - Resistance distributions of the random resistor network near the percolation threshold. PMID- 9994287 TI - Local-moment enhancement in an Al74Mn20Si6 quasicrystal induced by nonmagnetic iron doping. PMID- 9994289 TI - Exact diagonalization of finite frustrated spin-(1/2 Heisenberg models. PMID- 9994290 TI - Monte Carlo study of surface phase transitions in the three-dimensional Ising model. PMID- 9994291 TI - Dynamics of first-order transitions in two-dimensional systems with long-range interactions. PMID- 9994292 TI - Anisotropic magnetic susceptibility of hexagonal Co-based diluted magnetic semiconductors. PMID- 9994293 TI - Kinetics of slow domain growth: The n=1/4 universality class. PMID- 9994294 TI - Monte Carlo renormalization-group study of domain growth in the Potts model on a triangular lattice. PMID- 9994295 TI - Quantum Monte Carlo study of quasiparticles in the Hubbard model. PMID- 9994296 TI - Extension of the random-phase-approximation theory of ferromagnetism in a magnetic field applicable at all temperatures. PMID- 9994297 TI - Principles and possibilities of interferential multilayer mirrors of nonintegral dimensionality. PMID- 9994298 TI - Magnetic structures of PrFeSi2 and NdFeSi2 from neutron and Mossbauer studies. PMID- 9994299 TI - Large-S analysis of one-dimensional quantum-spin models in a transverse magnetic field. PMID- 9994300 TI - Quantum lattice fluctuations in the one-dimensional molecular-crystal model with Coulomb repulsion. PMID- 9994301 TI - Current distributions in anisotropic superconductors in the presence of grain boundaries. PMID- 9994302 TI - Two-photon spectroscopy in GdAlO3. PMID- 9994303 TI - Proximity effect in superconducting bilayers and multilayers. PMID- 9994304 TI - Flux nucleation in Josephson junctions formed by touching lead pieces. PMID- 9994306 TI - Critical indices for high-Tc superconductors. PMID- 9994305 TI - Anomalous Raman spectra from La2CuO4. PMID- 9994308 TI - Path-integral approach to density fluctuations in self-trapping systems. PMID- 9994307 TI - Infrared synchrotron-radiation transmission measurements on YBa2Cu3O7- delta in the gap and supercurrent regions. PMID- 9994309 TI - Reanalysis of a stacked triangular Ising antiferromagnet by use of Monte Carlo simulations. PMID- 9994311 TI - Statistical mechanics of ampiphilic dimers on a square lattice. PMID- 9994310 TI - Phase diagram for the domain-wall lattice of krypton on graphite. PMID- 9994312 TI - Optical study of the one-dimensional Ising-like antiferromagnet CsCoBr3. PMID- 9994313 TI - Diluted and random-bond Ising model: Application to the Fe-Mn-Al alloys. PMID- 9994315 TI - Comment on "Observation of trapped O2 in high-Tc metal oxide superconductors" PMID- 9994314 TI - Unbridled growth of spin-glass clusters. PMID- 9994316 TI - Reply to the "Comment on 'Observation of trapped O2 in high-Tc metal oxide superconductors' " PMID- 9994317 TI - Erratum: Phenomenological description of piezoresistivity in semiconducting perovskite ferroelectrics PMID- 9994318 TI - Erratum: Fluctuation effects in heavy-fermion and high-Tc superconductors PMID- 9994319 TI - Critical behavior of the surface-layer magnetization at the extraordinary transition in the three-dimensional Ising model. PMID- 9994320 TI - Ne** autoionizing states and Ne+ charge fractions scattered from a magnesium surface. PMID- 9994321 TI - Selection rules in resonance electron scattering from adsorbed molecules. PMID- 9994322 TI - Effects of zinc substitution on the electron superconductor Nd1.85Ce0.15CuO4- delta. PMID- 9994323 TI - Magnetic ordering in (Y1-xPrx)Ba2Cu3O7 as observed by muon-spin relaxation. PMID- 9994324 TI - Transport in the superconducting mixed state of Bi2+xSr2-yCuO6+/- delta. PMID- 9994325 TI - Specific heat of superconducting kappa -(BEDT-TTF)2Cu(NCS)2 near Tc PMID- 9994327 TI - Universal reduction of Tc in strong-coupling superconductors by a small concentration of magnetic impurities. PMID- 9994326 TI - Polarized resonance photoemission for Nd2CuO4. PMID- 9994328 TI - Density of bound states in a vortex core. PMID- 9994329 TI - Temperature dependence of anisotropic lower critical fields in (La1-xSrx)2CuO4. PMID- 9994330 TI - Renormalized mean-field theory of flux phases. PMID- 9994331 TI - Metal-insulator transition in amorphous Ga-Ar mixtures: Critical exponents of electrical transport parameters and behavior of superconductivity. PMID- 9994332 TI - Flux creep and the nature of a flux bundle in high-Tc thin films. PMID- 9994333 TI - Antiferromagnetism of CuO2 layers within a slave-boson approach. PMID- 9994334 TI - Stability of the ferromagnetic state with respect to a single spin flip: Variational calculations for the U= PMID- 9994335 TI - Determination of lattice structure and calculation of molecular tilt in lipid monolayers on water using x-ray diffraction. PMID- 9994336 TI - Unifying trends found for the VNO2N-1 series by the application of hydrostatic pressure. PMID- 9994337 TI - New approach to critical dynamic scaling in random magnets. PMID- 9994338 TI - Solvable model of the quantum spin glass in a transverse field. PMID- 9994340 TI - Rigorous bounds on the susceptibilities of the Hubbard model. PMID- 9994339 TI - Phase transition and non-Ohmic electrical transport in the spin-density-wave state of the organic conductor tetramethyltetraselenafulvalinium hexafluorophosphate PMID- 9994341 TI - Ultrasonic study of crossover behavior near the chiral multicritical point of CsNiCl3. PMID- 9994342 TI - Quantum renormalizations in the spin-1 Heisenberg antiferromagnet on the square lattice. PMID- 9994343 TI - Determination of electron momentum densities by a ( gamma,e gamma ) experiment. PMID- 9994344 TI - Domain-growth kinetics of Ag on Ge(111). PMID- 9994345 TI - Unoccupied electronic band structure of an ordered potassium layer on copper: Cu(111)-(2 x 2)K. PMID- 9994346 TI - Mesoscopic noise studies of atomic motions in cold amorphous conductors. PMID- 9994347 TI - Atomic and electronic structure of the NiAl(111) surface. PMID- 9994348 TI - Energetics and electronic structure of In on a Cu(100) surface. PMID- 9994350 TI - Full-potential multiple-scattering theory. PMID- 9994349 TI - Electronic structures of the stage-1 hydrogen-potassium-graphite ternary intercalation compounds C4KHx. PMID- 9994351 TI - Magnetic properties of CoCl2-graphite intercalation compounds under pressure. PMID- 9994352 TI - Electrical and thermal properties of fluorine-intercalated graphite fibers. PMID- 9994353 TI - Adsorption of bismuth onto the Au(111) surface. PMID- 9994354 TI - Theory of scanning-tunneling-microscopy images of intercalated graphite surfaces. PMID- 9994355 TI - Light scattering by surface acoustic waves on corrugated metal surfaces. PMID- 9994357 TI - Phase stability and magnetism of Ni3Al. PMID- 9994356 TI - Vacuum-ultraviolet reflectance and photoemission study of the metal-insulator phase transitions in VO2, V6O13, and V2O3. PMID- 9994358 TI - Larmor waves in single-crystal copper at 80 GHz. PMID- 9994359 TI - Surface photoemission and inverse photoemission in a periodic-cluster model of bcc iron: A many-body solution. PMID- 9994360 TI - Optical studies of electron and hole Fermi seas in a single GaAs/AlxGa1-xAs quantum well. PMID- 9994361 TI - Atomic structure of the Si(001)-(2 x 1) surface. PMID- 9994362 TI - Theory of the conductance of parallel ballistic constrictions. PMID- 9994363 TI - Theory of oxide defects near the Si-SiO2 interface. PMID- 9994364 TI - Band structure of metallic trans-polyacetylene with alkali-metal doping. PMID- 9994365 TI - Silicon dioxide defects induced by metal impurities. PMID- 9994367 TI - Shallow donor impurities in GaAs-Ga1-xAlxAs quantum-well structures: Role of the dielectric-constant mismatch. PMID- 9994366 TI - Far-infrared magneto-optical study of holes and electrons in zero-band-gap HgTe/Cd0.85Hg0.15Te superlattices. PMID- 9994368 TI - Electronic properties of n-i-p-i structures in elemental Si/Ge strained-layer superlattices. PMID- 9994369 TI - Linear optical properties of strained (Si)n/(Ge)n superlattices on (001) Si substrates. PMID- 9994370 TI - Characterization of some quaternary defect chalcopyrites as useful nonlinear optical and solar-cell materials. PMID- 9994372 TI - Growth of bismuth films on GaAs(110) studied using low-energy electron diffraction. PMID- 9994371 TI - Photoionization of deep impurity centers in semiconductors. PMID- 9994373 TI - Transport of an optically generated electron-hole plasma in a semiconductor slab: Approach to stationarity. PMID- 9994374 TI - Far-infrared absorption of neutron-transmutation-doped germanium. PMID- 9994375 TI - Noise spectroscopy as a tool to investigate the temperature dependence of localization in a quantum Hall system. PMID- 9994376 TI - Stark ladders in strongly coupled superlattices and their interactions with embedded quantum wells. PMID- 9994377 TI - Relaxation of stored charge carriers in a Zn0.3Cd0.7Se mixed crystal. PMID- 9994378 TI - Optical transitions in semiconductor superlattices with zinc-blende structure in the k PMID- 9994379 TI - Electron density correlation function of the two-dimensional electron gas in AlxGa1-xAs/GaAs heterojunctions. PMID- 9994380 TI - Spectroscopy and defect states in polyaniline. PMID- 9994381 TI - Determination of the bulk band structure of Ag in Ag/Cu(111) quantum-well systems. PMID- 9994383 TI - Influence of temperature and pressure on the electronic transitions in SnS and SnSe semiconductors. PMID- 9994382 TI - Raman scattering in long-period superlattices of GaAs, AlAs, and Ga0.5Al0.5As layers. PMID- 9994384 TI - Phenomenological description of ion-beam-induced epitaxial crystallization of amorphous silicon. PMID- 9994386 TI - Nonclassical scattering dynamics in the quantum Hall regime. PMID- 9994385 TI - Atomic structure of Si and Ge surfaces: Models for (113), (115), and stepped (001) vicinal surfaces. PMID- 9994388 TI - Mechanism of orthoexciton-to-paraexciton conversion in Cu2O. PMID- 9994387 TI - Positron annihilation and conductivity measurements on poly(pyrrole tosylate) and poly(pyrrole fluoride). PMID- 9994389 TI - Behavior of electron-irradiation-induced defects in GaAs. PMID- 9994390 TI - Electron transmission through silicon stacking faults. PMID- 9994391 TI - Fine structure of excitons in type-II GaAs/AlAs quantum wells. PMID- 9994392 TI - Abrupt interfaces with novel structural and electronic properties: Metal-cluster deposition and metal-semiconductor junctions. PMID- 9994393 TI - Valence-bond model for silicon force fields. PMID- 9994394 TI - Dispersion relations of low-energy branches in the vibrational spectrum of cleaved GaAs(110). PMID- 9994396 TI - Interpretation of Raman spectra of Ge/Si ultrathin superlattices. PMID- 9994395 TI - CaF2/Si heteroepitaxy: Importance of stoichiometry, interface bonding, and lattice mismatch. PMID- 9994397 TI - Light-hole contribution to noise and diffusion in p-type germanium at low temperatures. PMID- 9994399 TI - Hopping far-infrared magnetoabsorption in Cd1-xMnxSe and other mixed crystals. PMID- 9994398 TI - Quantization of the conductance of ballistic point contacts beyond the adiabatic approximation. PMID- 9994400 TI - Fluorescence mechanisms in Tm3+ singly doped and Tm3+, Ho3+ doubly doped indium based fluoride glasses. PMID- 9994401 TI - Pressure dependence of the 4T2 and 4T1 absorption bands of ruby to 35 GPa. PMID- 9994402 TI - Dispersion and localization of guided acoustic modes in a Langmuir-Blodgett film studied by surface-plasmon-polariton-enhanced Brillouin scattering. PMID- 9994403 TI - Upper limit on cold fusion in thin palladium films. PMID- 9994405 TI - Collective excitations in the fractional quantum Hall effect in an alternating density superlattice. PMID- 9994404 TI - Measurement and tentative analysis of resonant scattering features of He on the strongly corrugated Pt(110)-(1 x 2) surface. PMID- 9994407 TI - Growth of local structure in colloidal suspensions. PMID- 9994406 TI - Electrical properties of Cd1-xFexSe. PMID- 9994408 TI - Comment on "Ab initio pseudopotential calculations of optical-phonon deformation potentials in zinc-blende semiconductors" PMID- 9994409 TI - Erratum: Electronic structure of (diamond C)/(sphalerite BN) (110) interfaces and superlattices PMID- 9994410 TI - Low-temperature epitaxial growth of thin metal films. PMID- 9994411 TI - Generalized separable potentials for electronic-structure calculations. PMID- 9994412 TI - Adsorption-induced relaxation of Ni(001)-c(2 x 2)-O. PMID- 9994413 TI - Oxygen chemisorption on Cu(110): A structural determination by x-ray diffraction. PMID- 9994414 TI - Multiple sulfur sites in the Cu(100)p(2 x 2)-S surface structure. PMID- 9994416 TI - Low-energy electron-diffraction crystallographic determination for the Cu(110)2 x 1-O surface structure. PMID- 9994415 TI - High-field magnetotransport and Fermi-surface topology in the novel quasi-two dimensional organic conductor bis(ethylenedithiolo)tetrathiafulvalenium mercuric postassium thiocyanate, (BEDT-TTF)2KHg(SCN)4. PMID- 9994417 TI - Femtosecond dynamics of the n=2 image-potential state on Ag(100). PMID- 9994418 TI - Collective oscillations in a disordered two-dimensional electron gas at strong magnetic fields. PMID- 9994419 TI - Vacancy complexes in GaAs: Effects on impurity compensation. PMID- 9994421 TI - Thermoelectric Onsager coefficients of Rb0.3MoO3 in the depinned charge-density wave state. PMID- 9994420 TI - Copper, lithium, and hydrogen passivation of boron in c-Si. PMID- 9994422 TI - Dynamic photoinduced low-temperature oxidation of GaAs(110). PMID- 9994424 TI - Inter-valence-band scattering and cooling of hot holes in p-type germanium studied by picosecond infrared pulses. PMID- 9994423 TI - Resonant tunneling through one- and zero-dimensional states constricted by AlxGa1 xAs/GaAs/AlxGa1-xAs heterojunctions and high-resistance regions induced by focused Ga ion-beam implanation. PMID- 9994425 TI - Electronic modes and infrared optical excitation in tunneling superlattices. PMID- 9994426 TI - Electronic structure and optical properties of LiB3O5. PMID- 9994427 TI - Numerical test of universal conductance fluctuations. PMID- 9994428 TI - Transmission through a one-dimensional Fibonacci sequence of delta -function potentials. PMID- 9994429 TI - Morphological instability of a terrace edge during step-flow growth. PMID- 9994430 TI - Polarization effects in inverse-photoemission spectra from Ni(110). PMID- 9994431 TI - Charge transfer and the nature of empty states in potassium-intercalated graphite. PMID- 9994432 TI - 3d core-level photoemission spectra of intermetallic Yb compounds. PMID- 9994433 TI - Effect of the electron-phonon coupling on the shallow donor impurity state near a polar crystal surface. PMID- 9994434 TI - Rhombohedral to simple-cubic phase transition in arsenic under pressure. PMID- 9994435 TI - Localization, mobility edges, and metal-insulator transition in a class of one dimensional slowly varying deterministic potentials. PMID- 9994437 TI - Harmonic generations in an optical Fibonacci superlattice. PMID- 9994436 TI - Alkali-metal clusters: An s-band uncorrelated versus (s+p) highly correlated problem. PMID- 9994438 TI - Multiple final states in Ce 5p photoemission spectra. PMID- 9994439 TI - 1/f noise: A nonlinear-generalized-Langevin-equation approach. PMID- 9994440 TI - Dissociation channels of NaN+ clusters (3 <= N <= 37). PMID- 9994441 TI - Collective excitations of magnetoplasma in truncated metallic superlattices. PMID- 9994442 TI - Ab initio electronic-structure calculations on the Nb/Zr multilayer system. PMID- 9994443 TI - Parametrized linear muffin-tin orbitals atomic-sphere approximation tight-binding scheme: The electronic structure of MoRu alloys. PMID- 9994445 TI - Variational description of small metal clusters. PMID- 9994444 TI - Structure and energetics of Nan-xLix (n <= 21) clusters. PMID- 9994446 TI - Surface phonon spectroscopy of Ni(111) studied by inelastic electron scattering. PMID- 9994447 TI - Atom-superposition and electron-delocalization tight-binding band theory. PMID- 9994448 TI - Structure of liquid equiatomic KSn and CsSn. PMID- 9994449 TI - Confluence of extended and localized states: Implications on the Mott-Cohen Fritzsche-Ovshinsky model. PMID- 9994450 TI - Planar-surface charge densities and energies beyond the local-density approximation. PMID- 9994451 TI - Palladium clusters on graphite: Evidence of resonant hybrid states in the valence and conduction bands. PMID- 9994452 TI - Magneto-optics near the L point of the Brillouin zone in semimagnetic semiconductors. PMID- 9994453 TI - Surface reconstructions of GaAs(100) observed by scanning tunneling microscopy. PMID- 9994454 TI - He-atom scattering study of the temperature-dependent charge-density-wave surface structure and lattice dynamics of 2H-TaSe2(001). PMID- 9994455 TI - Lattice dynamics of AgGaSe2. I. Experiment. PMID- 9994456 TI - Lattice dynamics of AgGaSe2. II. Theoretical aspects. PMID- 9994457 TI - Surface and thermodynamic interatomic force fields for silicon clusters and bulk phases. PMID- 9994458 TI - Steady-state level-anticrossing spectra for bound-exciton triplets associated with complex defects in semiconductors. PMID- 9994459 TI - Hot-exciton cascades in coupled quantum wells. PMID- 9994461 TI - Impact of the electronic structure on the solubility and diffusion of 3d transition elements in silicon. PMID- 9994460 TI - Plasmons in periodically modulated inversion layers. PMID- 9994462 TI - Wave propagation in a nonlinear periodic medium. PMID- 9994464 TI - Optical analyses of radiation effects in ion-implanted Si: Fractional-derivative spectrum methods. PMID- 9994463 TI - Investigation of momentum relaxation and time-dependent conductance in radiation damaged GaAs. PMID- 9994465 TI - Fe3+ as near-infrared luminescence center in ZnS. PMID- 9994466 TI - Epitaxial Sn and Bi on GaAs(110): Inverse photoemission, shallow core-hole emission, and Ga 3d excitons. PMID- 9994467 TI - Microscopic theory of optic-phonon Raman scattering in quantum-well systems. PMID- 9994468 TI - Theory of the band-tail absorption saturation in polar semiconductors. PMID- 9994469 TI - Electronic structure of a-Si1-xNx:H and a-Ge1-xNx:H. PMID- 9994470 TI - Amorphous molybdenum silicide layers and Mo/Si(100) interface growth: Local structure and preparation dependence. PMID- 9994471 TI - Infrared study of (H,Be)-, (D,Be)-, and (Li,Be)-acceptor complexes in silicon. PMID- 9994472 TI - High-pressure Mossbauer study of SnSe. PMID- 9994473 TI - Comparison of the Harris and the Hohenberg-Kohn-Sham functionals for calculation of structural and vibrational properties of solids. PMID- 9994474 TI - Phonons in GaAs/AlAs superlattices grown along the PMID- 9994475 TI - Effect of polymer cross linking on the electrical properties of ethylenevinylacetate poly(3-octylthiophene) polymer blends. PMID- 9994476 TI - Relativistic band structure of Si, Ge, and GeSi: Inversion-asymmetry effects. PMID- 9994477 TI - Magnetoresistance and Hall effect near the metal-insulator transition of n-type Cd0.95Mn0.05Te. PMID- 9994478 TI - Second-order nonlinear optical susceptibility of a quantum well with an applied electric field. PMID- 9994479 TI - Band-gap narrowing in GaAs using a capacitance method. PMID- 9994480 TI - Thermally reversible band bending for Bi/GaAs(110): Photoemission and inverse photoemission investigations. PMID- 9994481 TI - Electronic structure of Cd1-xMnxS ternary semimagnetic alloys. PMID- 9994483 TI - Subband structure and plasmon-phonon coupled excitations in the accumulation layer of ZnO. PMID- 9994482 TI - Electronic structure of neutral and charged vacancies in GaAs. PMID- 9994485 TI - Interatomic interactions in covalent and ionic solids. PMID- 9994484 TI - Confined electron and hydrogenic donor states in a spherical quantum dot of GaAs Ga1-xAlxAs. PMID- 9994486 TI - Electronic band structure of the (GaAs)1/(InAs)1 (111) superlattice. PMID- 9994487 TI - Energy spectrum, transmittance, and localization in an incommensurate nonanalytic potential. PMID- 9994488 TI - Excitons in spatially separated ssV-shaped quantum wells: Application to GaAs sawtooth-doping superlattices. PMID- 9994489 TI - Raman microspectroscopy of diamond crystals and thin films prepared by hot filament-assisted chemical vapor deposition. PMID- 9994490 TI - Critical slowing down of low-frequency dielectric relaxation in incommensurate PMID- 9994491 TI - Raman and resonant Raman scattering from the HgTe/CdTe superlattice. PMID- 9994493 TI - Resonance-state calculation applying the Weyl-Titchmarsh theory: Application for the quantum-confined Stark effects on excitons in a GaAs-AlxGa1-xAs quantum well. PMID- 9994492 TI - Finite-basis many-electron approximation to the Anderson model. PMID- 9994494 TI - Zone-folded direct band gaps and energetics in strained (Si)4/(Ge)4 superlattices. PMID- 9994495 TI - Estimate of nuclear fusion rates arising from a molecular-dynamics model of PdDx. PMID- 9994496 TI - Ionization-energy dependence on GaAs(001) surface superstructure measured by photoemission-yield spectroscopy. PMID- 9994498 TI - Subband structure of strained-layer CdTe/ZnTe superlattices: A reexamination. PMID- 9994497 TI - Comparison between calculated and experimental values of the lowest excited electronic state of small CdSe crystallites. PMID- 9994499 TI - Room-temperature densification of a-SiO2 versus pressure. PMID- 9994501 TI - Photovoltaic effects in temperature-dependent Fermi-level movement for GaAs(110). PMID- 9994500 TI - Microscopic structure of the plasma resonance in charged potassium microclusters. PMID- 9994502 TI - K gaps for surface polaritons on gratings: Excitation by fast electrons. PMID- 9994504 TI - Slow-particle-induced kinetic electron emission from a clean metal surface: A comparison for neutral and ionized projectiles. PMID- 9994503 TI - Channeling of electrons in Si produces intense quasimonochromatic, tunable, picosecond x-ray bursts. PMID- 9994505 TI - Mossbauer-effect, magnetic, and neutron-diffraction study of NaFeP2O7. PMID- 9994506 TI - EPR study of Fe3+ in alpha -quartz: The sodium-compensated center. PMID- 9994507 TI - Magic-angle theorem in powder x-ray-absorption spectroscopy. PMID- 9994509 TI - Atomistic study of defects in YBa2Cu3O7. PMID- 9994508 TI - Mossbauer spectroscopy of 119Sn from implantations of radioactive 119Sb in metals. PMID- 9994510 TI - Infrared conductivity in superconductors with a finite mean free path. PMID- 9994511 TI - Phase boundary of superconducting networks: A new approximation scheme. PMID- 9994512 TI - Dissipation effects on superconducting arrays. PMID- 9994513 TI - Observation of the fcc-hcp 4He martensitic transformation morphology. PMID- 9994514 TI - Kosterlitz-Thouless transition in high-Tc superconductor films. PMID- 9994515 TI - Doping dependence of hole distribution in CuO2 planes of high-Tc superconductors: Local ansatz versus exact results. PMID- 9994516 TI - Optical coherent backscattering and transmission in a disordered medium near the mobility edge. PMID- 9994517 TI - Weak localization, fluctuation, and superconductivity in thin Nb films and wires. PMID- 9994518 TI - Phase locking between Josephson soliton oscillators. PMID- 9994519 TI - Sharp optical lines in rare-earth barium copper oxides. PMID- 9994520 TI - c-axis oxygen in copper oxide superconductors. PMID- 9994521 TI - Chiral liquid states in a spin-free representation for the diluted Mott insulator. PMID- 9994522 TI - Phenomenological model of nuclear relaxation in the normal state of YBa2Cu3O7. PMID- 9994524 TI - Fractional-statistics gas in the boson representation. PMID- 9994523 TI - Superconducting phases of Bi and Ga induced by deposition on a Ni sublayer. PMID- 9994525 TI - Far-infrared optical properties of superconducting Bi2Sr2CaCu2Ox films. PMID- 9994526 TI - Estimate of Z(2,4) for the loop-gas model on the honeycomb lattice. PMID- 9994527 TI - Closely coupled superconducting microbridges. PMID- 9994528 TI - Superfluid dynamics of the fractional quantum Hall state. PMID- 9994530 TI - Electron-electron interaction for the dynamical Jahn-Teller effect. PMID- 9994529 TI - Magnetic versus nonmagnetic ion substitution effects on Tc in the La-Sr-Cu-O and Nd-Ce-Cu-O systems. PMID- 9994532 TI - Static vacancies in antiferromagnetic La2CuO4 and superconducting La2-xSrxCuO4. PMID- 9994531 TI - Shadow wave-function variational calculations of crystalline and liquid phases of 4He. PMID- 9994533 TI - Onset of chaos in Josephson junctions with intermediate damping. PMID- 9994535 TI - Ab initio molecular-orbital study on electron correlation effects in CuO6 clusters relating to high-Tc superconductivity. PMID- 9994534 TI - Polarized copper K-edge x-ray-absorption spectra in YBa2Cu3O7-y. PMID- 9994536 TI - Tunnel creation of kink-antikink pairs from an inhomogeneous vacuum by an external field. PMID- 9994537 TI - Kinetics of diffusion-controlled oxygen ordering in a lattice-gas model of YBa2Cu3O7- delta. PMID- 9994538 TI - Theory for the temperature dependence of oxygen ordering in YBa2(Cu1-xMx)3O7-y due to impurities M=Al,Co,Fe. PMID- 9994539 TI - X-ray-absorption fine-structure studies of superconducting Tl2CaBa2Cu2Ox thin films. PMID- 9994540 TI - Ultrasonic study on Bi-based high-Tc superconductors with preferred orientations. PMID- 9994541 TI - Many-body derivation of quasiparticle bands and effective interactions of fermions in CuO2 layers. PMID- 9994542 TI - Electronic structure of the electron-doped superconductor Nd2-xCexCuO4-y studied by photoemission spectroscopy. PMID- 9994543 TI - Mean-field theories of cuprate superconductors: A systematic analysis. PMID- 9994544 TI - Superconductivity in the anyon model. PMID- 9994545 TI - Optically induced changes in the magnetic properties of the ceramic superconductor La1.8Ba0.2CuO4. PMID- 9994546 TI - Electronic properties of Ca2CuO2Cl2 and Ca2CuO2Br2. PMID- 9994547 TI - Electronic structure of the Ban+1PbnO3n+1 homologous series. PMID- 9994548 TI - Nonspherical rigid-muffin-tin calculations of electron-phonon coupling in high-Tc perovskites. PMID- 9994549 TI - Anisotropic superconductivity in extended t-J models. PMID- 9994551 TI - X-ray analysis of the incommensurate modulation in the 2:2:1:2 Bi-Sr-Ca-Cu-O superconductor including the oxygen atoms. PMID- 9994550 TI - High-resolution angle-resolved photoemission study of the Fermi surface and the normal-state electronic structure of Bi2Sr2CaCu2O8. PMID- 9994552 TI - Room-temperature oxygen diffusion and ordering in YBa2Cu3O7-y studied with time resolved Raman spectroscopy. PMID- 9994554 TI - Modification of the isotope effect due to energy-dependent electronic density of states. PMID- 9994553 TI - Hall effect and electronic structure of La2-xSrxCuO4. PMID- 9994555 TI - Magnetic anisotropy of high-Tc superconductors. PMID- 9994556 TI - Electron-energy-loss and optical-transmittance investigation of Bi2Sr2CaCu2O8. PMID- 9994557 TI - Positron annihilation studies in the Nd-Ce-Cu-O superconductor. PMID- 9994558 TI - Calculation of the electronic structure of YBa2(Cu1-xZnx)3O7 in terms of the real space-scattering coherent-potential approximation. PMID- 9994560 TI - NMR study of the ferroelastic-to-paraelastic protonic superionic transition in Rb3H(SeO4)2. PMID- 9994559 TI - Increased percolation threshold for 100-K superconductivity in lead-substituted Bi-Sr-Ca-Cu-O thin films. PMID- 9994561 TI - Magnetic phase transitions in narrow nondegenerate energy bands. PMID- 9994562 TI - Heisenberg and Ising spins in three dimensions with site-bond-correlated dilution. PMID- 9994563 TI - Small-cluster calculations for the simple and extended Hubbard models. PMID- 9994564 TI - Modeling electron-electron interactions in reduced-dimensional materials: Bond charge Coulomb repulsion and dimerization in Peierls-Hubbard models. PMID- 9994565 TI - Zero-temperature statics and dynamics of a random-exchange model for magnetic properties of La2-xSrxCuO4 in the insulating regime. PMID- 9994566 TI - Phonon dispersion and Kohn anomalies in Cu0.84Al0.16. PMID- 9994567 TI - Brillouin light-scattering experiments on exchange-coupled ultrathin bilayers of iron separated by epitaxial copper (001). PMID- 9994569 TI - Ferromagnetic resonance evidence for superparamagnetism in a partially crystallized metallic glass. PMID- 9994568 TI - Classical and quantum analysis of chaos in the discrete self-trapping equation. PMID- 9994570 TI - Electronic structure of YbN. PMID- 9994571 TI - Low-temperature behavior of random-anisotropy magnets. PMID- 9994572 TI - Interface roughening in the three-dimensional Ising model. PMID- 9994574 TI - Theory of semiclassical expansions for many-particle systems. PMID- 9994573 TI - Laser-melted amorphous and crystalline Fe-B alloys. PMID- 9994575 TI - Two-level system coupled to a boson mode. PMID- 9994576 TI - Superfluidity of the lattice anyon gas and topological invariance. PMID- 9994577 TI - Neutron-diffraction study of the commensurate-incommensurate phase transition of deuterium monolayers physisorbed on graphite. PMID- 9994579 TI - Photoemission study of the metal-nonmetal transition in NiS. PMID- 9994578 TI - Model for numerical evaluation of classical two-dimensional ion hopping transport in randomly nonuniform solids. PMID- 9994580 TI - Surface spin waves in Heisenberg ferromagnets with nonuniaxial single-ion anisotropy. PMID- 9994581 TI - Spin-dynamics study of the classical anisotropic XY chain. PMID- 9994582 TI - Proton glassy behavior in Rb1-x(NH4)xH2AsO4 mixed crystal. PMID- 9994584 TI - Phase transition and scaling properties of the energy spectrum for a hierarchical quantum Ising model. PMID- 9994583 TI - 3p and 3d core-level widths in metallic technetium: A study by internal conversion electron spectroscopy. PMID- 9994585 TI - Phase Hamiltonian and depinning electric field in the charge-density wave and the spin-density wave. PMID- 9994586 TI - Exact computer enumeration of the number of Hamiltonian paths in small plane square lattices. PMID- 9994587 TI - Magnetic susceptibilities, specific heat, and crystal structure of four S=3/2, three-dimensional antiferromagnets. PMID- 9994588 TI - Monte Carlo calculation of free energy for a fcc lattice-gas model. PMID- 9994589 TI - Low-index interfaces in Ising models: Macroscopic faceting, roughening, and phase diagrams. PMID- 9994590 TI - Comparison of melting in three and two dimensions: Microscopy of colloidal spheres. PMID- 9994592 TI - Scaling-law analysis to describe the impedance behavior of fractal electrodes. PMID- 9994591 TI - Domain growth in the two-dimensional time-dependent Ginzburg-Landau model in the presence of a random magnetic field. PMID- 9994593 TI - Dynamics of large-wave-vector magnons and phonons in MnF2:Er3+ using a far infrared quantum-counter technique. PMID- 9994595 TI - Thermodynamic properties of dilute CuCr alloys. PMID- 9994594 TI - X-ray study of the liquid and solid phases of the alkali metals in KC24- and RbC24-intercalated graphite single crystals. PMID- 9994596 TI - Solitonlike excitations in a spin chain with a biquadratic anisotropic exchange interaction. PMID- 9994597 TI - Theory of energy dissipation in sliding crystal surfaces. PMID- 9994598 TI - Dynamics of Heisenberg ferromagnets at low temperature. PMID- 9994599 TI - Metallic ferromagnetism in a single-band model. III. One-dimensional half-filled band. PMID- 9994600 TI - Incommensurate phases of quantum one-dimensional magnetics. PMID- 9994601 TI - Motion of a single hole in an itinerant-electron antiferromagnet. PMID- 9994602 TI - Nonuniversal anisotropy dependence of critical-wetting exponents in a vector model. PMID- 9994603 TI - Short-range antiferromagnetic ordering with spiral structure in the finite-doping regime. PMID- 9994604 TI - Dynamic correlations in a classical two-dimensional Heisenberg antiferromagnet. PMID- 9994605 TI - Low-temperature catalysis of para-deuterium to ortho-deuterium conversion on Grafoil. PMID- 9994606 TI - Spin-lattice coupling coefficients G11 and G44 for 6S-state ions in Td symmetry. PMID- 9994607 TI - Oscillatory lamellar microstructure in off-eutectic Al-Cu alloys. PMID- 9994609 TI - Direction of the magnetization of thin films and sandwiches as a function of temperature. PMID- 9994608 TI - Dynamics and phase transitions in solid ortho and para hydrogen and deuterium from an ab initio potential. PMID- 9994610 TI - Magnetic hysteresis in two model spin systems. PMID- 9994611 TI - Spin waves at the interface between two antiferromagnets. PMID- 9994612 TI - Quasiparticle properties in effective models for strongly correlated electrons. PMID- 9994614 TI - Laser-excited fluorescence and electron-spin resonance of Er3+ in polycrystalline AlCl3. PMID- 9994613 TI - Phenomenological study of the amorphous Fe80B20 ferromagnet with small random anisotropy. PMID- 9994615 TI - Nuclear-resonance photon-scattering study of the vibrational spectrum of NH3. PMID- 9994617 TI - dc Josephson current for very strong coupling. PMID- 9994616 TI - Local-structure model of K+ site in KTaO3:Fe3+ PMID- 9994619 TI - Inelastic Coulomb scattering between extended and localized electrons: A quasilinear temperature dependence. PMID- 9994618 TI - Optical characterization of excited states in BaBiO3. PMID- 9994620 TI - Macroscopic quantum tunneling in long Josephson junctions. PMID- 9994621 TI - Upper critical field in superconductors and the uncertainty principle: Upper limit to the maximum slope of Hc2. PMID- 9994622 TI - Excitonic pairing in electron-doped Cu-O layers. PMID- 9994624 TI - Identification of the 1250-cm-1 Raman feature in YBa2Cu3O6. PMID- 9994623 TI - X-ray photoelectron spectroscopy analysis of Bi2Sr2Ca1-xYxCu2Oy. PMID- 9994625 TI - Renormalized Bose condensation in the presence of fermions. PMID- 9994626 TI - Spin polarons in high-Tc copper oxides: Differences between electron- and hole doped systems. PMID- 9994627 TI - Logarithmic corrections in antiferromagnetic chains. PMID- 9994628 TI - Decomposition kinetics in Ni-Ti alloys. PMID- 9994629 TI - Nonclassical wetting behavior in the solid-on-solid limit of the three dimensional Ising model. PMID- 9994630 TI - Percolation and phase transitions of hard-core particles on lattices with pair interactions. PMID- 9994631 TI - Sequence of incommensurate phases in a model of surface reconstruction and roughening. PMID- 9994632 TI - Orbital magnetic moments in commensurate flux phases. PMID- 9994633 TI - Quantum size effect on the magnetism of finite systems. PMID- 9994634 TI - Pattern formation in phase-separating alloys with cubic symmetry. PMID- 9994636 TI - Analog simulation of melting in two dimensions. PMID- 9994635 TI - Absence of long-range order in three-dimensional spherical models. PMID- 9994638 TI - Erratum: "Monte Carlo of the growth of wetting layers" PMID- 9994637 TI - Quantum decay of a metastable state in a spin system. PMID- 9994639 TI - Erratum: "Monte Carlo studies of universal critical amplitudes for the three dimensional ising model: Correlation length and renormalized coupling" PMID- 9994640 TI - Spin dynamics and magnetic resonance in two-dimensional Heisenberg antiferromagnets. PMID- 9994641 TI - Angular anisotropy in ion-surface charge transfer. PMID- 9994642 TI - Tilt-modulus enhancement of the vortex lattice in the layered superconductor 2H NbSe2. PMID- 9994643 TI - Reduction of the magnetization decay rate in high-Tc superconductors. PMID- 9994644 TI - Constraints on s-wave pairing in the Hubbard model. PMID- 9994646 TI - Critical behavior of unconventional superconductors with quenched impurities. PMID- 9994645 TI - Recalculation of 4kF correlations in one-dimensional systems. PMID- 9994647 TI - Metastable effects and random polarities of magnetic moments in disordered systems of Josephson junctions. PMID- 9994648 TI - Role of the Cu-O charge-transfer energy in the superconductivity of cuprates: Evidence from Cu 2p core-level spectroscopy and theory. PMID- 9994649 TI - Motion of two holes in a quantum antiferromagnet. PMID- 9994650 TI - Phenomenological description of the copper oxides as almost localized Fermi liquids. PMID- 9994651 TI - Polarization x-ray-absorption near-edge structure study of Pr2-xCexCuO4 single crystals: The nature of Ce doping. PMID- 9994652 TI - YBa2Cu3O7-x (001) studied at 60 K with momentum-resolved inverse photoemission. PMID- 9994653 TI - High-energy spin excitations in the insulating phases of high-Tc superconducting cuprates and La2NiO4. PMID- 9994654 TI - Onset of valence and magnetic instabilities in the ferromagnetic semiconductor EuO at high pressures. PMID- 9994655 TI - Homogeneous nucleated annihilation of the 2q phase in Cu0.78Pd0.22. PMID- 9994656 TI - Ginzburg-Landau theory for mass transport in a driven diffusive system. PMID- 9994657 TI - Possible vortex-glass transition in a model random superconductor. PMID- 9994658 TI - Trace maps of general substitutional sequences. PMID- 9994660 TI - Evidence for a rhodium moment in amorphous (FexRh1-x)80B20 alloys. PMID- 9994659 TI - Magnetic anisotropy in epitaxial Co superlattices. PMID- 9994661 TI - Hubbard U= PMID- 9994662 TI - Missing modes in the density of states of fractal networks. PMID- 9994663 TI - Electronic effect of lead substitution in single-crystal Bi(Pb)-Sr-Ca-Cu-O superconductors determined by scanning tunneling microscopy. PMID- 9994665 TI - Energy gap of the S=1 antiferromagnetic Heisenberg chain. PMID- 9994664 TI - Two-dimensional ordering during droplet growth on a liquid surface. PMID- 9994666 TI - Planar channeling in superlattices. III. Potential and parameter dependence of catastrophic dechanneling. PMID- 9994667 TI - Absorption and emission spectroscopy of Eu3+ in metaphosphate glasses. PMID- 9994668 TI - NMR determination of the Edwards-Anderson order parameter in the deuterated pseudo-spin-glass Rb1-x(ND4)xD2PO4: Anisotropy and concentration dependence of the ND4+ deuteron second moment. PMID- 9994669 TI - Dephasing times of the vibrons in alpha -N2 and in alpha -(15N2)x(14N2)1-x mixed crystals. PMID- 9994670 TI - Anisotropy of momentum distributions in atomic-collision cascades generated in fcc materials. PMID- 9994671 TI - Decay-kinetics study of atomic hydrogen in a-Si:(H,O,N) and natural beryl. PMID- 9994672 TI - Slow-proton reemission from noble-gas solids. PMID- 9994674 TI - Inelastic-neutron-scattering study of methyl tunneling and the quantum sine Gordon breather in isotopic mixtures of 4-methyl-pyridine at low temperature. PMID- 9994673 TI - M and N core excitations in zirconium. PMID- 9994675 TI - Magnetic x-ray-scattering study of uranium arsenide. PMID- 9994676 TI - Variational Fermi-hypernetted-chain approximation PMID- 9994677 TI - Solution to Ginzburg-Landau equations for inhomogeneous superconductors by nonlinear optimization. PMID- 9994678 TI - Numerical study of long Josephson junctions coupled to a high-Q cavity. PMID- 9994679 TI - Effect of the operator nature of the superconducting order parameter in the presence of an added quasiparticle. PMID- 9994680 TI - Theory of nonlinear electromagnetic rectification in a BCS superconductor. PMID- 9994682 TI - Quantum diffusion and pairing of ortho-H2 impurities in para-H2. PMID- 9994681 TI - Effect of high pressure on the electrical resistivity of the heavy-fermion compound UBe13. PMID- 9994683 TI - Discontinuous change of superconducting transition temperature from BCS type to bipolaron type in strongly coupled electron-phonon systems. PMID- 9994684 TI - Behavior of excess electrons in a one-dimensional classical bath: Equilibrium properties. PMID- 9994685 TI - Exact solution of the mean-field theory for a heavy-fermion alloy in one dimension. PMID- 9994686 TI - High-pressure triple point in helium: The melting line of helium up to 240 kbar. PMID- 9994687 TI - Anyons on a torus. PMID- 9994689 TI - Localization of isolated holes in a Mott insulator and delocalization by pairing. PMID- 9994688 TI - Fluctuation-induced first-order transitions in unconventional superconductors. PMID- 9994690 TI - Minimal renormalization without epsilon expansion: Critical behavior above and below Tc. PMID- 9994691 TI - Solitary-wave propagation in superfluid 4He films. PMID- 9994692 TI - Static-hole energies in the t-J model and a t-J- epsilon model of the high temperature superconductors. PMID- 9994693 TI - Critical currents in frustrated two-dimensional Josephson arrays. PMID- 9994694 TI - New phases induced by hydrogen reduction and by subsequent oxidation of L2CuO4 (L=La,Pr,Nd,Sm,Eu,Gd). PMID- 9994695 TI - Flux motion, proximity effect, and critical current density in YBa2Cu3O7- delta /silver composites. PMID- 9994696 TI - Effect of the nearest-neighbor Coulomb interaction on d-wave Cooper pairing on a square lattice. PMID- 9994697 TI - Incorporation of gold into YBa2Cu3O7: Structure and Tc enhancement. PMID- 9994698 TI - Viscous flux motion in a Josephson-coupled layer model of high-Tc superconductors. PMID- 9994699 TI - Direct measurement of the anisotropy of the resistivity in the a-b plane of twin free, single-crystal, superconducting YBa2Cu3O7- delta. PMID- 9994700 TI - Hole motion in the t-J and Hubbard models: Effect of a next-nearest-neighbor hopping. PMID- 9994701 TI - Effects of the magnetic and thermal history in granular samples of Y-Ba-Cu-O and Bi-Sr-Ca-Cu-O: Experimental evidence of a sharp transition into a frozen state at low temperature. PMID- 9994702 TI - Renormalized band structure of CuO2 layers in superconducting compounds: A mean field approach. PMID- 9994703 TI - Transport properties of high-Tc superconductors: Fermi-liquid local-density electronic-structure predictions. PMID- 9994704 TI - Electromagnetic properties of stacks of superconducting layers. PMID- 9994705 TI - Possible origins of resistive tails and critical currents in high-temperature superconductors in a magnetic field. PMID- 9994706 TI - Millimeter-wave complex conductivity of some epitaxial YBa2Cu3O7- delta films. PMID- 9994708 TI - Cuprate parameters from numerical Wannier functions. PMID- 9994707 TI - Nernst effect by laser-pulse heating in Tl-Ba-Ca-Cu-O superconducting thin films. PMID- 9994709 TI - Incommensurate correlations in the t-J and frustrated spin-1/2 Heisenberg models. PMID- 9994711 TI - Delocalization of holes in La2-x(Ba,Sr)xCuO4. PMID- 9994710 TI - Inequivalent layers can cause flux-lattice melting in layered superconductors. PMID- 9994712 TI - Observation of temperature-dependent site disorder in YBa2Cu3O7- delta below 150 degreesC. PMID- 9994713 TI - Comparison of the empty electronic states of Bi2Sr2CaCu2O8 (001) and Bi2Sr2CuO6 (001) at 60 and 300 K. PMID- 9994715 TI - Neutron and synchrotron x-ray powder-diffraction study of La2CuO4+ delta. PMID- 9994714 TI - Effect of a geometrical length scale on remanent magnetization and critical currents in Y-Ba-Cu-O and Bi-Sr-Ca-Cu-O crystals. PMID- 9994716 TI - Frequency- and temperature-dependent conductivity in YBa2Cu3O6+x crystals. PMID- 9994717 TI - Influence of fluctuations on spin systems with spatially isotropic competing interactions. PMID- 9994718 TI - Momentum constraints in collective-variable theory. PMID- 9994719 TI - Core-level photoemission spectrum for the spin-degenerate Anderson model. PMID- 9994720 TI - Replica-symmetry breaking for the Ising spin glass in a transverse field. PMID- 9994721 TI - Quasi-one-dimensional solutions for domain walls and their constraints in improper ferroelastics. PMID- 9994722 TI - Gap states and localization properties of one-dimensional Fibonacci quasicrystals. PMID- 9994723 TI - Cooper-pairing interaction due to magnetic fluctuations near the spin-density wave phase transition. PMID- 9994724 TI - Lattice dynamics and origin of ferroelectricity in BaTiO3: Linearized-augmented plane-wave total-energy calculations. PMID- 9994725 TI - Suppression of staging in lithium-intercalated carbon by disorder in the host. PMID- 9994726 TI - Spatial chaos in a nonlinear monatomic chain. PMID- 9994727 TI - Scaling of spatiotemporal correlation in ordering dynamics. PMID- 9994728 TI - Initial- versus final-state effects in the narrow-band spectra of heavy-fermion systems. PMID- 9994729 TI - Equation of state of solid hydrogen and deuterium from single-crystal x-ray diffraction to 26.5 GPa. PMID- 9994731 TI - Monte Carlo simulation of strongly disordered Ising ferromagnets. PMID- 9994730 TI - Tensile-stress dependence of magnetostriction in multilayers of amorphous ribbons. PMID- 9994733 TI - Corrections to the Hall mobility. PMID- 9994732 TI - Sound speed and thermophysical properties of liquid iron and nickel. PMID- 9994734 TI - Imperfect nesting in quasi-one-dimensional charge- and spin-density waves. PMID- 9994735 TI - Fluid transport in partially filled porous sol-gel silica glass. PMID- 9994736 TI - Effective spin Hamiltonian for the CuO planes in La2CuO4 and metamagnetism. PMID- 9994737 TI - Spin dynamics of the itinerant helimagnet MnSi studied by positive muon spin relaxation. PMID- 9994738 TI - Doped antiferromagnets in the weak-hopping limit. PMID- 9994739 TI - Surface interaction energies in binary alloys from diffuse x-ray scattering. PMID- 9994741 TI - Wetting phenomena on rough substrates. PMID- 9994740 TI - Crystal structure, resistivity, magnetic susceptibility and heat capacity of a new dense Kondo system: CePtSi2. PMID- 9994742 TI - Existence of Neel order at T=0 in the spin-1/2 antiferromagnetic Heisenberg model on a square lattice. PMID- 9994743 TI - Exact diagonalization of quantum-spin models. PMID- 9994745 TI - Ordering due to disorder in dipolar magnets on two-dimensional lattices. PMID- 9994744 TI - Static magnetization direction under perpendicular surface anisotropy. PMID- 9994746 TI - Niobium hydride phase behavior studied using the cluster-variation method. PMID- 9994748 TI - Nucleation in a time-dependent Ginzburg-Landau model: A numerical study. PMID- 9994747 TI - Exact results for the U= PMID- 9994749 TI - Metallic non-Fermi-liquid fixed point in two and higher dimensions. PMID- 9994750 TI - Scaling properties of fracture toughness in random materials. PMID- 9994751 TI - Dual percolation threshold in two-dimensional microporous media. PMID- 9994753 TI - Coexistence-curve diameter and critical density of xenon. PMID- 9994752 TI - Unconventional structures and related physical properties of the semifluorinated triblock alkane C6F13-C4H8-C6F13. PMID- 9994755 TI - Magnetic dichroism in the x-ray-absorption branching ratio. PMID- 9994754 TI - Kinetics of quenched systems with long-range repulsive interactions. PMID- 9994757 TI - Magnetism of hexagonal 3d transition metals. PMID- 9994756 TI - Quantum statistical mechanics of nonlinear excitations in a model for structural phase transitions. PMID- 9994758 TI - Temperature dependence of hyperfine magnetic fields in Fe-Co alloys. PMID- 9994759 TI - Neutron diffraction and Mossbauer studies of Ga site preference in Nd2Fe14B and Fe internal-field assignments. PMID- 9994760 TI - Superconductivity in beta -di PMID- 9994761 TI - Quality of variational ground states for a two-state system coupled to phonons. PMID- 9994762 TI - Lattice specific heat of YBa2Cu3O7. PMID- 9994763 TI - Spirals and spin bags: A link between the weak- and the strong-coupling limits of the Hubbard model. PMID- 9994764 TI - Magnetoplasma waves in thin high-temperature-superconducting layers. PMID- 9994765 TI - Exotic quantum effects in two space dimensions: The role of translation invariance. PMID- 9994766 TI - Compressible spin models for plastic crystals. PMID- 9994768 TI - Breakup threshold of solitons in systems with nonconvex interactions. PMID- 9994767 TI - Parametric excitation of magnetostatic modes in circular ferromagnetic films. PMID- 9994769 TI - Positron annihilation studies of an icosahedral quasicrystal and the cubic R phase of Al-Li-Cu. PMID- 9994770 TI - Proton-glass state in K0.60(NH4)0.40H2AsO4 detected by dielectric measurements. PMID- 9994771 TI - Crystal structures of group IVa metals at ultrahigh pressures. PMID- 9994773 TI - Comment on "Finite-size effects at temperature-driven first-order transitions" PMID- 9994772 TI - One-dimensional-lattice spin models with long-range antiferromagnetic interactions. PMID- 9994774 TI - Erratum: Muon-spin-relaxation and neutron-scattering studies of magnetism in single-crystal La1.94Sr0.06CuO4 PMID- 9994775 TI - Evidence for structural relaxation in measurements of hydrogen diffusion in rf sputtered boron-doped a-Si:H. PMID- 9994777 TI - Hyper-resistivity to global-superconductivity transition by annealing in quench condensed Pb films. PMID- 9994776 TI - Analytical photon scanning tunneling microscopy. PMID- 9994778 TI - Superconducting effective-mass anisotropy in Tl2Ba2CaCu2Ox. PMID- 9994780 TI - Nature and stability of the "60-K superconducting phase" in the YBa2Cu3O7- delta system. PMID- 9994779 TI - Magnetic quantization and the upper critical field of superconductors. PMID- 9994782 TI - Anisotropic properties of La8-xSrxCu8O20- delta epitaxial thin films. PMID- 9994781 TI - Holes in antiferromagnets: Pairing interaction. PMID- 9994783 TI - Flux-flow Nernst effect in epitaxial YBa2Cu3O7. PMID- 9994784 TI - 139La NMR study of phase separation in single-crystal La2CuO4+ delta. PMID- 9994786 TI - Dynamics of quasiparticles in the two-dimensional Hubbard model. PMID- 9994785 TI - Universality in the current decay and flux creep of Y-Ba-Cu-O high-temperature superconductors. PMID- 9994788 TI - Interstitial oxygen and high-temperature superconductivity in La2-xSrxCuO4+ delta. PMID- 9994787 TI - Electron destruction in a fractionized system. PMID- 9994789 TI - Flux pinning and irreversibility in YBa2Cu3O7 superconducting crystal. PMID- 9994791 TI - Anisotropic gap and quasiparticle-damping effects on NMR measurements of high temperature superconductors. PMID- 9994790 TI - Magnetic penetration depth of Y1-xPrxBa2Cu3O6.97 measured by muon-spin relaxation. PMID- 9994792 TI - Binding of holes in one-dimensional Hubbard chains. PMID- 9994793 TI - Magnetic properties of Nd2CuO4-type R2CuO4 (R=Y, Dy, Ho, Er, Tm) synthesized under high pressure: Weak ferromagnetism of Y2CuO4. PMID- 9994794 TI - Analysis of the core-level photoemission spectra of the superconducting cuprates: Evidence for a strongly mixed-valent state. PMID- 9994796 TI - Effect of spin-orbit and spin-flip scattering on conductance fluctuations. PMID- 9994795 TI - Magnetization of single-crystal erbium. PMID- 9994797 TI - Kosterlitz-Thouless transition in the two-dimensional quantum XY model. PMID- 9994799 TI - Criterion for a good variational wave function. PMID- 9994798 TI - Electrical-resistivity and ac-susceptibility measurements on Ni-Mn and Ni-Mn-Pt ternary alloys. PMID- 9994800 TI - Experimental evidence for the existence of exchange-dominated collective spin wave excitations in multilayers. PMID- 9994801 TI - Hybridization gap in Ce3Bi4Pt3. PMID- 9994802 TI - Short-time relaxation at polymeric interfaces. PMID- 9994803 TI - Single spin flip in the Nagaoka state: Problems with the Gutzwiller wave function. PMID- 9994804 TI - Photoinduced valence instability in the organic molecular compound tetrathiafulvalene-p-chloranil (TTF-CA). PMID- 9994805 TI - Nuclear antiferromagnetism in copper: Interplay of (0,2/3,2/3) and (1,0,0) order. PMID- 9994807 TI - Monitoring low-coverage surface chemistry with bulk transport: NO2 dissociation and oxygen penetration at a GaAs(110) surface. PMID- 9994806 TI - Phase diagram of the frustrated square Heisenberg lattice based upon a modified spin-wave theory. PMID- 9994808 TI - Quantum Hall effect in a self-similar system. PMID- 9994809 TI - Renormalization group for growth kinetics in the large-N limit. PMID- 9994810 TI - Hole-hole effective interaction in the two-dimensional Hubbard model. PMID- 9994811 TI - Finite-size-scaling study of the simple cubic three-state Potts glass: Possible lower critical dimension d=3. PMID- 9994812 TI - Embedded-atom-method study of coherency and elastic moduli of Pd-Cu multilayers. PMID- 9994813 TI - Galvanomagnetic phenomena and surface roughness in thin metallic films. PMID- 9994814 TI - Coordinate-permutable cubic harmonics and their determination. PMID- 9994815 TI - Chemical modification of positronium formation at metal surfaces. PMID- 9994817 TI - Deviation of spin susceptibility of small metallic particles as predicted by the random-matrix theory. PMID- 9994816 TI - Structural and electronic properties of the liquid polyvalent elements. II. The divalent elements. PMID- 9994818 TI - Commensurability transitions in multilayers: A response to substrate-induced elastic stress. PMID- 9994819 TI - Oxygen-induced missing-row reconstruction of Cu(001) and Cu(001)-vicinal surfaces. PMID- 9994820 TI - Some phonon effects in S(q) for bcc metals. PMID- 9994821 TI - Core polarization and the dielectric response of simple metals. PMID- 9994822 TI - Transformations preceding amorphization in Cr-Ti and Cr-Ti-Fe beta phases. PMID- 9994823 TI - Surface relaxation in c(2 x 2)Cl/Ni(100) determined by the soft-x-ray standing wave method combined with surface-extended x-ray-absorption fine-structure spectroscopy. PMID- 9994825 TI - Plasmons in a superlattice with periodic defects. PMID- 9994824 TI - Local density of states for transition-metal interfaces. PMID- 9994826 TI - Subpicosecond luminescence study of tunneling and relaxation in coupled quantum wells. PMID- 9994828 TI - Envelope-function approximation for nonrectangular Hg1-xCdxTe superlattices. PMID- 9994827 TI - Phonon frequencies for Si-Ge strained-layer superlattices calculated in a three dimensional model. PMID- 9994829 TI - Long-range ordering of Sb multilayers on GaAs(110): Evolution of resonant inverse photoemission. PMID- 9994831 TI - Effect of collisions and relaxation on coherent resonant tunneling: Hole tunneling in GaAs/AlxGa1-xAs double-quantum-well structures. PMID- 9994830 TI - Picosecond electron-hole droplet formation in indirect-gap AlxGa1-xAs. PMID- 9994832 TI - Electric-field effects on shallow impurity states in GaAs-(Ga,Al)As quantum wells. PMID- 9994833 TI - Phonon-drag thermoelectric power in AlxGa1-xAs/GaAs heterojunctions at low temperatures. PMID- 9994834 TI - Exciton binding energies in semiconductor superlattices: An anisotropic-effective medium approach. PMID- 9994836 TI - Generalized Franz-Keldysh theory of electromodulation. PMID- 9994835 TI - Interplanar forces and phonon spectra of strained Si and Ge: Ab initio calculations and applications to Si/Ge superlattices. PMID- 9994837 TI - Optical properties of liquid Se-Te alloys. PMID- 9994838 TI - Carrier relaxation and luminescence polarization in quantum wells. PMID- 9994839 TI - Nonlinear optical properties of GaAs/Ga1-xAlxAs superlattices. PMID- 9994841 TI - Electronic structure of beta -FeSi2. PMID- 9994840 TI - Density of states and thermodynamic properties of a two-dimensional electron gas in a strong external magnetic field. PMID- 9994842 TI - Nonvariational numerical calculations of excitonic properties in quantum wells in the presence of strain, electric fields, and free carriers. PMID- 9994843 TI - Theory for the instability of the diamond structure of Si, Ge, and C induced by a dense electron-hole plasma. PMID- 9994844 TI - Stability of DX centers in AlxGa1-xAs alloys. PMID- 9994846 TI - Thermal-expansion anisotropy in the quaternary semiconductor CuGaGe1-x(VGe)xSe4 at elevated temperatures. PMID- 9994845 TI - Analysis of the fractional-quantum-Hall-effect ground state in the symmetric gauge. PMID- 9994847 TI - Random-Bethe-lattice model applied to the electronic structure of amorphous and liquid silicon. PMID- 9994848 TI - Self-consistent unifying theory of the electronic structure of metal semiconductor systems. PMID- 9994849 TI - Line shapes of intersubband and excitonic recombination in quantum wells: Influence of final-state interaction, statistical broadening, and momentum conservation. PMID- 9994850 TI - Vibrational properties versus on- and off-axis behavior of the FA(Li+) center in alkali halides. PMID- 9994851 TI - Evidence for trimer reconstruction of Si(111) sqrt 3 x sqrt 3 -Sb: Scanning tunneling microscopy and first-principles theory. PMID- 9994852 TI - Vibrational evidence of surface reconstruction in the Ni(100)/O system obtained using high-resolution electron-energy-loss spectroscopy. PMID- 9994853 TI - Commensurate reconstruction on a (001) facet of a gold particle. PMID- 9994854 TI - Low-energy cathodoluminescence experiment with polarized electrons and a negative electron-affinity GaAs target. PMID- 9994855 TI - Identification of bonded species in hydrogenated fluorinated amorphous silicon. PMID- 9994856 TI - Entropy of a Frenkel pair in silicon. PMID- 9994857 TI - Quantum size effects on the exciton energy of CdS clusters. PMID- 9994859 TI - Erratum: Impurity photoconductivity spectra of ZnGa2Se4:Co2+ single crystals PMID- 9994858 TI - Lattice dynamics of superlattices with interface roughness. PMID- 9994860 TI - Erratum: Confirmation of the temperature-dependent photovoltaic effect on Fermi level measurements by photoemission spectroscopy PMID- 9994861 TI - Soft-x-ray magnetic circular dichroism at the L2,3 edges of nickel. PMID- 9994862 TI - Universal dependence on the average conductance of conductance fluctuations in disordered metals. PMID- 9994863 TI - First-principles calculation of the magnetic anisotropy energy of (Co)n/(X)m multilayers. PMID- 9994865 TI - Annealing-temperature influence on the dispersive diffusion of hydrogen in undoped a-Si:H. PMID- 9994864 TI - Band-gap renormalization in direct-band-gap AlxGa1-xAs. PMID- 9994866 TI - Photoluminescence from the quasi-two-dimensional electron gas at a single silicon delta -doped layer in GaAs. PMID- 9994867 TI - Dynamics of exciton localization in a CdSe0.5S0.5 mixed crystal. PMID- 9994868 TI - Scanning-tunneling-microscopy study of InSb(110). PMID- 9994869 TI - Intrinsic bistability in resonant-tunneling structures. PMID- 9994871 TI - Derivation of response equations for the nondestructive probing of charge and polarization profiles. PMID- 9994870 TI - Angular distribution of Rh atoms desorbed from ion-bombarded Rh{100}: Effect of local environment. PMID- 9994872 TI - Electronic structure and related properties of silver. PMID- 9994873 TI - Structure and phases of the Au(001) surface: In-plane structure. PMID- 9994874 TI - Quasimomentum in the theory of elasticity and its conservation. PMID- 9994875 TI - Interpretation of substrate photoelectron diffraction. PMID- 9994876 TI - Green's function and a generalized Lloyd formula for the density of states in disordered muffin-tin alloys. PMID- 9994878 TI - Many-body calculations on the valence photoemission of NiCO and Ni(CO)4. PMID- 9994877 TI - Theory of reflection high-energy electron diffraction. PMID- 9994879 TI - Theory of the thermal boundary resistance between dissimilar lattices. PMID- 9994881 TI - Electric-field effects on the charge-transfer excitation in quasi-one-dimensional halogen-bridged mixed-valence Pt complexes: PMID- 9994880 TI - New formalism for determining excitation spectra of many-body systems. PMID- 9994883 TI - Inverse photoemission from electronic surface states: Intensity, angular, and polarization dependence. PMID- 9994882 TI - Two-dimensional treatment of nonlinear thermoelectricity in homogeneous metals. PMID- 9994884 TI - Electromagnetic response of quantum dots. PMID- 9994885 TI - Potential fluctuations due to inhomogeneity in hydrogenated amorphous silicon and the resulting charged dangling-bond defects. PMID- 9994886 TI - Complete valence-band structure of Ge determined by photoemission. PMID- 9994887 TI - Dynamics of exciton formation and relaxation in GaAs quantum wells. PMID- 9994888 TI - Observation of single-electron-tunneling oscillations. PMID- 9994890 TI - Nonrelativistic zitterbewegung in two-band systems. PMID- 9994889 TI - State filling, Coulomb, and trapping effects in the optical nonlinearity of CdTe quantum dots in glass. PMID- 9994892 TI - Ab initio calculation of properties of carbon in the amorphous and liquid states. PMID- 9994891 TI - First-principles pseudopotential calculations of the elastic properties of diamond, Si, and Ge. PMID- 9994893 TI - Atomic structure of Si(111)-( sqrt 3 x sqrt 3 )R30 degrees-Al studied by dynamical low-energy electron diffraction. PMID- 9994895 TI - Resonatorless optical bistability in direct-band-gap semiconductors as an example of bistability driven by a phase transition. PMID- 9994894 TI - Cu and Ag deposition on layered p-type WSe2: Approaching the Schottky limit. PMID- 9994897 TI - Analytical technique for extracting the eigenvalues of the k PMID- 9994896 TI - Excitons bound to nitrogen pairs in GaAs. PMID- 9994898 TI - Synchrotron-radiation photoemission study of CdS/CuInSe2 heterojunction formation. PMID- 9994900 TI - Bonding and structures in silicon clusters: A valence-bond interpretation. PMID- 9994899 TI - Scanning tunneling microscopy of a stage-1 CuCl2 graphite intercalation compound. PMID- 9994901 TI - Effects of surface defects on the shallow states of donor impurities at semiconductor surfaces. PMID- 9994903 TI - Magnetoreflectance and magnetization of the semimagnetic semiconductor Cd1 xFexSe. PMID- 9994902 TI - X-ray photoelectron spectroscopic studies of conductive polypyrrole complexes chemically synthesized with FeCl3. PMID- 9994904 TI - Spin-dependent electron transition processes related to excited triplet spin states of neutral complex defects in silicon studied by optically detected magnetic resonance. PMID- 9994905 TI - Electronic structure of MnO. PMID- 9994907 TI - Calorimetric investigations of (NaCN)1-x(KCN)x glasses. PMID- 9994906 TI - Electronic structure of yttrium oxide. PMID- 9994908 TI - [H-Ca+]0 defect in thermochemically reduced CaO: A static and dynamical EPR study. PMID- 9994909 TI - Near-surface Raman scattering in germanium clusters and ultrathin amorphous films. PMID- 9994910 TI - Instanton Aharonov-Bohm effect and macroscopic quantum coherence in charge density-wave systems. PMID- 9994911 TI - Site-dependent electronic effects, forces, and deformations in scanning tunneling microscopy of flat metal surfaces. PMID- 9994912 TI - Decay of molecules at spherical surfaces: Nonlocal effects. PMID- 9994913 TI - Confinement effects on the low-field-high-field correspondences of hydrogenic impurity states in quasi-two-dimensional systems. PMID- 9994914 TI - Quasibound states in an electric field. PMID- 9994915 TI - Edge channels and the role of contacts in the quantum Hall regime. PMID- 9994916 TI - Magnetoplasmons in an electron gas at the crossover from two- to one-dimensional behavior. PMID- 9994918 TI - Size effects and charge-density-wave pinning in Nb1-xTixSe3: Evidence for weak pinning by a nonisoelectronic impurity. PMID- 9994917 TI - Comment on "Effect of biaxial strain on acceptor-level energies in InyGa1 yAs/AlxGa1-xAs (on GaAs) quantum wells" PMID- 9994919 TI - Persistent currents in mesoscopic metallic rings: Ensemble average. PMID- 9994921 TI - Observation of transient band-gap renormalization in quantum wells. PMID- 9994920 TI - Vibrational properties of metastable diatomic hydrogen complexes in crystalline silicon. PMID- 9994922 TI - Impurity enhancement of hopping parameters in conducting polymers. PMID- 9994923 TI - Ballistic-hole spectroscopy of interfaces. PMID- 9994924 TI - Femtosecond energy transfer in a-Si:H. PMID- 9994926 TI - Quantum point contact as a local probe of the electrostatic potential contours. PMID- 9994925 TI - Covalency in the adsorption of Na on Si(111). PMID- 9994927 TI - Positron spectroscopy of solid N2. PMID- 9994929 TI - Polarization of radiation from axially channeled electrons. PMID- 9994928 TI - Perturbed-angular-correlation measurements of trivalent indium defects in silver chloride. PMID- 9994930 TI - Nuclear-magnetic-resonance studies of hydrogen antitrapping effects by impurities (Mn,Cr,Fe) in zirconium dihydride. PMID- 9994931 TI - Time-domain analysis of the dynamics of Frenkel excitons in disordered systems. PMID- 9994932 TI - Momentum distributions of H2 monolayers on Grafoil. PMID- 9994933 TI - Cross relaxation between proton and quadrupolar nuclear spins in metal-hydrogen systems. PMID- 9994934 TI - Electron-spin-resonance study of Tl0 centers of the laser-active type structure in SrCl2. PMID- 9994935 TI - EPR study of defect reorientation by a tunneling-controlled process. PMID- 9994937 TI - 27Al nuclear-spin dephasing in the ruby frozen core and Cr3+ spin-flip-time measurements. PMID- 9994936 TI - Neutralization of low-energy D+ scattered from solid surfaces. PMID- 9994938 TI - EPR studies of AsO44- spin-lattice-relaxation times in antiferroelectric NH4H2AsO4 and mixed glassy Rb1-x(NH4)xH2AsO4 (x=0.35). PMID- 9994940 TI - 39K NMR determination of the soliton density in K2SeO4. PMID- 9994939 TI - EPR study of K2SeO4:Cu2+ in the high-temperature phase and in the incommensurate phase. PMID- 9994941 TI - Long-range exchange interaction in (2,2'-bipyridine-3,3'-dicarboxylic acid)dichlorocopper(II) monohydrate via lattice water: Single-crystal EPR studies. PMID- 9994943 TI - Critical temperature of superconductors: Exact solution from Eliashberg equations on the weak-coupling side. PMID- 9994942 TI - 19F NMR studies in ABF4-type layered antiferromagnets. PMID- 9994944 TI - Third-sound propagation in thick films of superfluid 4He. PMID- 9994945 TI - Pairing ground states in fermion systems: A static method. PMID- 9994946 TI - Logarithmic effects on the critical behavior of superfluids in random media. PMID- 9994947 TI - Picosecond dynamics of degenerate orthoexcitons in Cu2O. PMID- 9994948 TI - Determination of the Cooper-pair mass in niobium. PMID- 9994950 TI - Effect of disorder on a system of flux lines. PMID- 9994949 TI - Self-consistent mean-field approach for the ideal anyon gas. PMID- 9994951 TI - Two-dimensional ion-plasma resonances under the surface of liquid helium. PMID- 9994952 TI - Polarization dependence of the Cu 2p absorption spectra in (Bi0.84Pb0.16)2Sr2CaCu2O8. PMID- 9994953 TI - Evidence of low-dimensional antiferromagnetic ordering and crystal structure in the R2BaNiO5 (R=Y,Er) oxides. PMID- 9994955 TI - Orbital ferromagnetism of anyons. PMID- 9994954 TI - Dynamics of oxygen in the YBa2Cu3O7-x basal planes by elastic-energy-loss measurements. PMID- 9994956 TI - Raman scattering in the t-J model with doping. PMID- 9994957 TI - Thermodynamic reversibility in the superconducting fluctuation regime. PMID- 9994959 TI - Phonon spectroscopy of superconducting Nb using point-contact tunneling. PMID- 9994958 TI - Influence of hydrogen on the 89Y NMR in HxYBa2Cu3O7. PMID- 9994961 TI - Spectral function and photoemission spectra in antiferromagnetically correlated metals. PMID- 9994960 TI - Quadrupolar-fluctuation model for high-Tc superconductivity: A quantum Monte Carlo study. PMID- 9994962 TI - Angle-resolved photoemission spectra of high-Tc superconductors: A Fermi-liquid based analysis. PMID- 9994963 TI - Magnetic order and electronic phase diagrams of electron-doped copper oxide materials. PMID- 9994964 TI - Application of the polaron-transport theory to sigma ( omega ) in Tl2Ba2Ca1 xGdxCu2O8, YBa2Cu3O7- delta, and La2-xSrxCuO4. PMID- 9994965 TI - Incommensurate flux phases on a square lattice. PMID- 9994966 TI - Oxygen-nonstoichiometry effect on the superconducting properties of the Sr-free Bi cuprates. PMID- 9994967 TI - Critical-current diffraction patterns of grain-boundary Josephson weak links. PMID- 9994969 TI - Synthesis and superconducting properties of Y(Ba1-yLay)2Cu4O8 and (Y1-xCax)(Ba1 yLay)2Cu4O8. PMID- 9994968 TI - Muon-spin-rotation measurements of the London penetration depths in YBa2Cu3O6.97. PMID- 9994970 TI - Specific-heat jump at Tc for Nd1.85Ce0.15CuO4-y. PMID- 9994971 TI - Annihilation of superconductivity by Co substitution for Cu in Nd1.85Ce0.15CuO4. PMID- 9994973 TI - Electron-tunneling studies on the superconducting (La1-xSrx)2CuO4 and YBa2Cu3Oy systems. PMID- 9994972 TI - Variation of Cu-O charge-transfer energies in YBa2Cu3O7-x thin films studied by photoemission spectroscopy. PMID- 9994975 TI - Electron- and hole-doped high-temperature superconductors: A common charge transfer model. PMID- 9994974 TI - High-resolution electron-energy-loss study of the surfaces and energy gaps of cleaved high-temperature superconductors. PMID- 9994976 TI - Positron-annihilation study of oxygen-deficient YBa2Cu3Ox (6.3fcc phase transitions in Pd thin films. PMID- 9995434 TI - Destruction of fractional quantum Hall effect in thick systems. PMID- 9995437 TI - Ground-state structures and the random-state energy of the Madelung lattice. PMID- 9995436 TI - Molecular-beam-epitaxial growth and magnetic properties of Co-Pt superlattices oriented along the PMID- 9995438 TI - Optical studies of the piezoelectric effect in (111)-oriented CdTe/Cd1-xZnxTe strained quantum wells. PMID- 9995439 TI - Radiative decay of excitonic states in bulklike GaAs with a periodic array of InAs lattice planes. PMID- 9995441 TI - Dimensionality effects on the interband magnetoelectroabsorption of semiconductor superlattices. PMID- 9995440 TI - Self-consistent far-infrared response of quantum-dot structures. PMID- 9995442 TI - Large magnetic depopulation of multiple parallel ballistic point contacts with circulating channels. PMID- 9995443 TI - Electron transport with two occupied subbands in a Si(100) inversion layer. PMID- 9995444 TI - Electron interactions in the two-dimensional electron-gas base of a vertical hot electron transistor. PMID- 9995445 TI - Bulk-doping-controlled implantation site of boron in silicon. PMID- 9995446 TI - Effects of local environment on localized vibrational modes of aluminum in AlxGa1 xAs. PMID- 9995447 TI - Transient band bending in a staggered-alignment type-II multiple-quantum-well structure. PMID- 9995448 TI - Triply resonant Raman scattering by LO phonons in a Wannier-Stark ladder. PMID- 9995449 TI - Determination of Xz-Xx,y energy separation and intervalley relaxation times in type-II AlxGa1-xAs/AlAs multiple quantum wells. PMID- 9995450 TI - Statics and dynamics of icosahedrally twinned and single-crystal fcc clusters. PMID- 9995451 TI - Bond softening in monolayer graphite formed on transition-metal carbide surfaces. PMID- 9995452 TI - Multiprobe electron waveguides: Filtering and bend resistances. PMID- 9995453 TI - Quantum-mechanical propagation of electrons through a kink and the Anderson localization problem. PMID- 9995454 TI - Pseudopotentials with position-dependent electron masses. PMID- 9995455 TI - Structural and electronic properties of the liquid polyvalent elements. III. The trivalent elements. PMID- 9995456 TI - Surface relaxation of alpha -iron and the embedded-atom method. PMID- 9995457 TI - Theory of nonlinear surface magneto-optics for ferromagnetic nickel: Effects of band structure and matrix elements. PMID- 9995458 TI - Thin Cu/Ag(111) and Ag/Cu(111) structures studied with monoenergetic positrons. PMID- 9995459 TI - Universal nature of self-bound potential systems: Diatomic molecules, surface adsorptions, and bulk cohesions. PMID- 9995460 TI - Three-dimensional positron-electron momentum distribution in single-crystal graphite. PMID- 9995461 TI - Hall effect in Zr-Ni and Zr-Cu metallic glasses doped with hydrogen. PMID- 9995462 TI - X-ray-diffraction study of in-plane and interlayer correlations in layered compounds AgxTiS2. PMID- 9995463 TI - Static electric polarizabilities of sodium clusters. PMID- 9995464 TI - Optical-absorption spectra of CsFeCl3 PMID- 9995465 TI - Optical-absorption spectra of CsFeCl3 PMID- 9995466 TI - Stabilized jellium: Structureless pseudopotential model for the cohesive and surface properties of metals. PMID- 9995467 TI - Total-energy calculations of solid H, Li, Na, K, Rb, and Cs. PMID- 9995469 TI - Model for phonon transmission through a NbN grain-size distribution: Comparison with tunneling-spectroscopy observations. PMID- 9995468 TI - Absorptive potentials due to ionization and thermal diffuse scattering by fast electrons in crystals. PMID- 9995470 TI - Raman scattering in CdF2:In crystals. PMID- 9995471 TI - Photoexcited states in poly(p-phenylene vinylene): Comparison with trans,trans distyrylbenzene, a model oligomer. PMID- 9995472 TI - Influence of surfactants in Ge and Si epitaxy on Si(001). PMID- 9995473 TI - Microstructure and strain relief of Ge films grown layer by layer on Si(001). PMID- 9995474 TI - Exciton binding energy in type-II heterojunctions. PMID- 9995475 TI - Collective modes in quantum-dot arrays in magnetic fields. PMID- 9995476 TI - Room-temperature resonant multiphotonic optical pumping induced by 10.6- microm laser radiation in reverse-biased n+/p-type Si junctions. PMID- 9995477 TI - Resonant first- and second-order Raman scattering in AlSb. PMID- 9995478 TI - Coulomb-interaction effects on the excited states of double acceptors in germanium and silicon. PMID- 9995479 TI - Localized interstitial states in tetrahedrally bonded semiconductors: The local matrix approach. PMID- 9995480 TI - Formation mechanisms of localized interstitial states in tetrahedrally bonded semiconductors. PMID- 9995481 TI - Fractional dimensionality and fractional derivative spectra of interband optical transitions. PMID- 9995482 TI - Atomic-force-microscopy images of graphite due to van der Waals interactions. PMID- 9995483 TI - Optically induced excess hole population in semi-insulating GaAs. PMID- 9995484 TI - Exchange interaction in a quantum wire in a strong magnetic field. PMID- 9995485 TI - Simple method for calculating exciton binding energies in quantum-confined semiconductor structures. PMID- 9995486 TI - Excitonic effects in the optical spectra of superlattices in an electric field. PMID- 9995487 TI - Donor states in GaAs under hydrostatic pressure. PMID- 9995488 TI - Molecular-beam study of sticking of oxygen on Si(100). PMID- 9995489 TI - Optically detected magnetic resonance of Si donors in AlxGa1-xAs. PMID- 9995490 TI - Valley-mixing effects in (GaAs)l(AlAs)m superlattices with microscopically imperfect interfaces. PMID- 9995491 TI - Electrical, optical, and magnetic properties of poly(2,5-diethoxy-p-phenylene vinylene). PMID- 9995492 TI - Effect of inhomogeneous charge distribution on the cyclotron resonance in an inverted GaAs/Ga1-xAlxAs interface. PMID- 9995493 TI - Surface electronic structure of K on Si(111)2 x 1 as a function of potassium coverage. PMID- 9995494 TI - Radiative recombination center in As2Se3 as studied by optically detected magnetic resonance. PMID- 9995495 TI - Reversible photoinduced change of photoconductivity in amorphous chalcogenide films. PMID- 9995496 TI - Metastable effects in hydrogenated amorphous silicon-silicon nitride multilayers. PMID- 9995497 TI - Electronic structure of the silicon divacancy. PMID- 9995498 TI - One-phonon resonant Raman scattering in AlxGa1-xAs (0.56A1(6S) photoluminescence band in Zn0.5Mn0.5Se. PMID- 9995607 TI - Positron mobility in Si at 300 K. PMID- 9995608 TI - Conductance fluctuations in large metal-oxide-semiconductor structures in the variable-range hopping regime. PMID- 9995610 TI - Electron-nuclear double-resonance and electron-spin-resonance study of silicon dangling-bond centers in silicon nitride. PMID- 9995609 TI - Transport and optical properties of low-resistivity CdSe. PMID- 9995611 TI - Electronic structures and optical properties of short-period GaAs/AlAs superlattices. PMID- 9995612 TI - Quantum-mechanical description of ions in crystals: Electronic structure of magnesium oxide. PMID- 9995613 TI - Symmetry and distribution of two-level systems in glasses. PMID- 9995614 TI - Structural and elastic properties of sodium halides at high pressure. PMID- 9995615 TI - Photoemission study of CoO. PMID- 9995617 TI - Existence of acoustic interface waves in sandwich structures. PMID- 9995616 TI - Ultraviolet inverse-photoemission spectroscopy of Gd silicides. PMID- 9995618 TI - Different approach to the theory of the quantum Hall effect. PMID- 9995619 TI - Excitons in resonant coupling of quantum wells. PMID- 9995620 TI - Estimate of phonon thermal transport in amorphous materials above 50 K. PMID- 9995622 TI - Oxygen effectiveness in restructuring the Ag(110) surface: The p(3 x 1)O chemisorbed phase. PMID- 9995621 TI - Local symmetry breaking in stage-1 alkali-metal-graphite intercalation compounds studied by scanning tunneling microscopy. PMID- 9995623 TI - Potassium- and sodium-induced phonons on the reconstructed and unreconstructed copper (110) surface studied by high-resolution electron-energy-loss spectroscopy. PMID- 9995624 TI - Theory of anomalous corrugation of the Al(111) surface obtained from scanning tunneling microscopy. PMID- 9995625 TI - Amphoteric behavior of H0 in GaAs. PMID- 9995626 TI - Existence of two adsorbed states for K on the Si(100)(2 x 1) surface: A thermal desorption study. PMID- 9995628 TI - Temperature dependence of low-energy positron-induced Auger-electron emission: Evidence for high surface sensitivity. PMID- 9995627 TI - Low-temperature photoemission measurements of valence-band discontinuities at buried heterojunctions. PMID- 9995629 TI - Temperature dependence of the nuclear quadrupole interactions at Ti sites in ferroelectric PbTiO3 and in ilmenite and perovskite CdTiO3: Evidence for order disorder phenomena. PMID- 9995630 TI - Molecular-dynamics study of electronic sputtering of large organic molecules. PMID- 9995631 TI - Correlation-crystal-field analysis of the 2H(2)11/2 multiplet of Nd3+ PMID- 9995632 TI - Reemitted positron spectroscopy of near-surface defects. PMID- 9995633 TI - Bulk and local elastic relaxation around optically excited centers. PMID- 9995635 TI - NMR studies of vacancy motion in solid hydrogen. PMID- 9995634 TI - Determination of the magnitude and sign of the 185,187Re nuclear electric quadrupole coupling constants using nuclear acoustic resonance. PMID- 9995636 TI - Observation of intermultiplet transitions in SmFe11Ti by inelastic magnetic neutron scattering. PMID- 9995638 TI - Plasmons in cuprate superconductors. PMID- 9995637 TI - Multichannel multiple-scattering theory with general potentials. PMID- 9995639 TI - Effects of quasiparticle dissipation on quantum fluctuations in granular superconductors. PMID- 9995640 TI - Soft-x-ray absorption spectroscopy of electron-doped (Nd,Sm)2-xCexCuO4- delta compounds. PMID- 9995641 TI - Thermal accommodation of spin-polarized hydrogen on liquid-He surfaces below 0.25 K. PMID- 9995643 TI - Possible phase diagrams of superconducting UPt3. PMID- 9995642 TI - Stability of charged thin helium films. PMID- 9995644 TI - Properties of the flux-line lattice in anisotropic superconductors near Hc2. PMID- 9995645 TI - Upper critical field of s- and d-wave superconductors with anisotropic effective mass. PMID- 9995646 TI - Vortex pinning in Josephson-junction arrays. PMID- 9995647 TI - Charge distribution and electric-field gradients in YBa2Cu3O7-x. PMID- 9995648 TI - Temperature and field dependence of magnetic relaxation in a Bi2Sr2CaCu2Ox single crystal. PMID- 9995649 TI - Theory of superconducting proximity effect in a three-dimensional system in the clean limit. PMID- 9995651 TI - Two-dimensional localized vibrational modes of trans-(CH)x around a polaron. PMID- 9995650 TI - Phase diagram of 3He-4He mixture films. PMID- 9995652 TI - Quantum tunneling of surface-state electrons. PMID- 9995653 TI - Damping of spin waves in a two-dimensional Heisenberg antiferromagnet at low temperatures. PMID- 9995654 TI - Elastic properties of a two-dimensional lattice in a weak random pinning potential: Origin of the pinning force. PMID- 9995655 TI - Superconductivity in a two-band Hubbard model. PMID- 9995656 TI - Local structure about Ni atoms in Ni-substituted YBa2Cu3O7- delta. PMID- 9995657 TI - Thermally activated flux creep in strongly layered high-temperature superconductors. PMID- 9995658 TI - Interatomic potential, phonon spectrum, and molecular-dynamics simulation up to 1300 K in YBa2Cu3O7- delta. PMID- 9995659 TI - Weak-link structure in YBa2Cu3O7 single crystals: A microwave study. PMID- 9995660 TI - Superconductivity above 100 K by Pr substitution in the two-copper-layer Bi-Pb-Sr Ca-Cu-O system. PMID- 9995661 TI - Magnetic order and superconductivity in YBa2Cu3-yMyOz (M=Fe,Co). PMID- 9995662 TI - Superconducting correlations in the two-band Hubbard model. PMID- 9995664 TI - Mossbauer spectroscopy of CuO and its relevance to high-temperature superconductors. PMID- 9995663 TI - Muon-spin-rotation studies in single-crystal Sr2CuO2Cl2. PMID- 9995665 TI - Temperature dependence of positron annihilation parameters in Tl-Ba-Ca-Cu-O superconductors. PMID- 9995666 TI - Charge-transfer and magnetic-pairing mechanisms in the extended Hubbard model of high-Tc oxides. PMID- 9995667 TI - Electromagnetic response of high-Tc superconductors. PMID- 9995668 TI - Finite-size studies of particles obeying fractional statistics. PMID- 9995670 TI - Kosterlitz-Thouless transition and conductivity fluctuations in Y-Ba-Cu-O thin films. PMID- 9995669 TI - X-ray absorption near-edge studies of substitution for Cu in YBa2(Cu1-xMx)3O7- delta (M=Fe, Co, Ni, and Zn). PMID- 9995671 TI - X-ray photoelectron spectroscopy study of YBa2Cu3-xFexO7+y. PMID- 9995673 TI - Superconducting states of an extended Hubbard model. PMID- 9995672 TI - Relationship between superconductivity and crystalline stability of the Y-Ba-Cu-O system. PMID- 9995674 TI - Resonant photoemission study of the electronic structure of CuO and Cu2O. PMID- 9995676 TI - Anomalous decouplings and the fermion sign problem. PMID- 9995675 TI - Late stages of delta ' precipitation in an Al-Li alloy by small-angle neutron scattering. PMID- 9995677 TI - Existence of an internal quasimode for a sine-Gordon soliton. PMID- 9995678 TI - Vibrational relaxation and dephasing of two-phonon bound states in molecular crystals. PMID- 9995679 TI - Long-range magnetic order in very dilute YEr alloys. PMID- 9995680 TI - Concentrated spin-glass behavior in Al37Mn30Si33 quasicrystals. PMID- 9995682 TI - Dynamical pair susceptibilities in the t-J and Hubbard models. PMID- 9995681 TI - Atomic short-range-order structure in Au-Fe alloys. PMID- 9995684 TI - Crystal-field and configuration dependence of hopping-matrix elements for CeCu2Si2. PMID- 9995683 TI - Spinodal decomposition in a two-dimensional fluid model: Heat, sound, and universality. PMID- 9995685 TI - Electronic and magnetic structures of Fe/Cr/Fe sandwiches and Fe/Cr superlattices. PMID- 9995687 TI - Random-field Blume-Capel model: Mean-field theory. PMID- 9995686 TI - Temperature-induced neutral-ionic transition in tetramethylbenzidine tetracyanoquinodimethane (TMB-TCNQ). PMID- 9995688 TI - Density of states for elementary excitations in the Kondo problem. PMID- 9995689 TI - Finite-size effects in Cu-Mn spin glasses. PMID- 9995690 TI - Pairing and charge-density-wave correlations in the Holstein model at half filling. PMID- 9995691 TI - Magnetization measurements and computer simulations for the magnetic hysteresis losses of reentrant Ni100-xMnxPt and Ni-Mn alloys. PMID- 9995692 TI - Exact treatment of three-body bound states in a one-dimensional model of ionic crystals. PMID- 9995694 TI - Numerical determination of the phase diagram for the cphi4 model in two dimensions. PMID- 9995693 TI - Monte Carlo transfer-matrix study of the frustrated XY model. PMID- 9995695 TI - Low-temperature specific heat of the diluted magnetic semiconductor Hg1-x yCdyFexSe. PMID- 9995696 TI - Three-state antiferromagnetic Potts models: A Monte Carlo study. PMID- 9995697 TI - Atomic vibrations in a self-consistent-field atom-in-jellium model of condensed matter. PMID- 9995699 TI - Finite-resolution effects on the logarithm-of-the-current distribution in fractal structures. PMID- 9995698 TI - Mobile vacancy in a quantum antiferromagnet: Effective Hamiltonian. PMID- 9995700 TI - Stability and first-order phase transitions. PMID- 9995702 TI - Critical behavior of the layer-compressional elastic modulus at a smectic-smectic isolated critical point. PMID- 9995701 TI - Hopping conductivity of the interacting honeycomb lattice gas. PMID- 9995703 TI - Quadratic quantum antiferromagnets in the fermionic large-N limit. PMID- 9995704 TI - Yield strength of Al2O3 at high pressures. PMID- 9995705 TI - Covalence in CuCl2 PMID- 9995706 TI - Electron depolarization by inelastic exchange scattering from Cr3+ magnetic moments. PMID- 9995707 TI - Effects of correlation and disorder on the phase diagram of YBa2Cu3O6+x. PMID- 9995708 TI - Resonating-valence-bond ground state in a large-n t-J model. PMID- 9995709 TI - Magnetic properties of polycrystalline Ba0.5K0.5BiO3. PMID- 9995710 TI - Effect of Ni and Zn substitution on magnetic properties of the high-Tc superconductor GdBa2Cu3O7-y. PMID- 9995712 TI - Dispersive single-particle excitations in high-Tc copper oxides. PMID- 9995711 TI - Magnetic interactions of Gd in GdBa2(Cu1-xNix)3Oy compounds. PMID- 9995713 TI - Simple approximation for the transition to vortex-glass superconductivity. PMID- 9995714 TI - Enhanced ultrasonic attenuation of Tl-Ca-Ba-Cu-O at the superconducting transition. PMID- 9995715 TI - Negative thermopower of YbBa2Cu3O7-y. PMID- 9995717 TI - Stretched-exponential behavior in Ising critical dynamics. PMID- 9995716 TI - Scaling theory of the Mott transition. PMID- 9995718 TI - Antiferromagnetic phase transition in Cd1-xMnxSe epilayers. PMID- 9995719 TI - Structural transition study of NiCl2 PMID- 9995720 TI - Critical exponents of the vortex glass to order epsilon 3. PMID- 9995721 TI - Spin-wave theory of the Haldane gap in one-dimensional antiferromagnets. PMID- 9995722 TI - Variational results as saddle-point approximations: The Anderson impurity model. PMID- 9995723 TI - Phase diagram of a trimodal random-field spin-S Ising model. PMID- 9995724 TI - Spin-1 and mixed-spin Ising model in a transverse field. PMID- 9995725 TI - Path-integral representation and critical properties of the quantum Potts model. PMID- 9995727 TI - Regular fractal models of snowflakes and critical dynamics of the kinetic Ising model on fractals. PMID- 9995726 TI - Pressure dependence of free-energy expansion coefficients in PbTiO3 and BaTiO3 and tricritical-point behavior. PMID- 9995729 TI - Erratum: "Superconducting pairing of holes in the antiferromagnetic state of the two-dimensional Hubbard model" PMID- 9995728 TI - Erratum: Anomalous and subanomalous diffusion in stochastic trapping transport PMID- 9995730 TI - Erratum: "Magnon damping in the two-dimensional quantum Heisenberg antiferromagnet at short wavelengths PMID- 9995731 TI - Universal polarization correlations and microstatistics of optical waves in random media. PMID- 9995732 TI - Defect pair creation through ultraviolet radiation in dense, amorphous SiO2. PMID- 9995734 TI - Two crucial experimental tests of the resonating valence bond-Luttinger liquid interlayer tunneling theory of high-Tc superconductivity. PMID- 9995733 TI - Scatterer correlation effects on photon transport in dense random media. PMID- 9995735 TI - Torque creep in high-Tc superconductors. PMID- 9995736 TI - Interaction of vortices in uniaxial superconductors. PMID- 9995737 TI - X-ray-absorption studies of Y-Ba-Cu-O and Bi-Sr-Ca-Cu-O films at oxygen K edge by means of fluorescence and total electron yield: A comparison of two techniques. PMID- 9995738 TI - Dependence of flux-creep activation energy upon current density in grain-aligned YBa2Cu3O7-x. PMID- 9995739 TI - Behavior of the Raman continuum and Raman "gap" in Tc=60 K YBa2Cu3O7- delta. PMID- 9995740 TI - Phase fluctuations in two-dimensional superconducting weakly coupled wire networks. PMID- 9995741 TI - Inverse ac Josephson effect in long junctions. PMID- 9995742 TI - Supersolitons in layered Josephson structures. PMID- 9995743 TI - Resistive transition curves in magnetic fields for Tl2Ba2Can-1CunOy (n=1, 2, 4) compounds: Dependence on the number of Cu-O layers. PMID- 9995744 TI - Phases of the t-J model from variational Monte Carlo studies: Occurrence of time reversal symmetry breaking. PMID- 9995745 TI - Monte Carlo study of superconductivity in the three-band Emery model. PMID- 9995746 TI - Superconductive transition at 98.5 K in monoclinic (Bi,Pb)2Sr2CaCu2Oy. PMID- 9995747 TI - Novel magnetic structure of a vortex lattice in adsorbed 3He films. PMID- 9995748 TI - Heisenberg magnets with short-range order and spin dynamics of YBa2Cu3O6+x. PMID- 9995749 TI - Magnetic instabilities in unconventional superconductors. PMID- 9995750 TI - Thermal conductivity of Ba-K-Bi-O: A contrast to copper oxide superconductors. PMID- 9995752 TI - Optical near-zone-center phonons and their interaction with electrons in YBa2Cu3O7: Results of the local-density approximation. PMID- 9995751 TI - Observation of Cu NMR in antiferromagnetic PrBa2Cu3O7: Evidence for hole-band filling. PMID- 9995753 TI - Theoretical electron-positron zone-reduced momentum density for YBa2Cu3O7: Fermi surface and wave-function effects. PMID- 9995755 TI - Quantum correlation effects in the spin dynamics of Gd at high temperatures in the light of complex dilation theory. PMID- 9995754 TI - Valence-fluctuation behavior of Yb ions and YbCuGa. PMID- 9995756 TI - Orbital magnetism in Fe, Co, and Ni. PMID- 9995757 TI - Thermodynamics and phase diagram of multilayer krypton on graphite. PMID- 9995758 TI - Magnetic susceptibility of CsMnBr3 near the tetracritical point. PMID- 9995759 TI - Nonperturbative approach to the Newns-Anderson model of chemisorption. PMID- 9995760 TI - Temperature and magnetic field dependence of the two-dimensional conductivity in AuxSi1-x/Si and Cu/Si multilayers. PMID- 9995761 TI - Conductance fluctuations and 1/f noise in Bi. PMID- 9995762 TI - Theoretical study of the magnetic x-ray dichroism of Os, Ir, Pt, and Au impurities in Fe. PMID- 9995763 TI - Metallization pressure for NaCl in the B2 structure. PMID- 9995764 TI - Electronic structure of ordered and disordered Cu alloys: Cu3Pd, Cu3Pt, and Cu3Au. PMID- 9995765 TI - Charge-distribution changes accompanying the formation and changes in the composition of HfCx and TaCx. PMID- 9995766 TI - Stiffness reduction associated with charge-density-wave sliding: Temperature and bias dependences in TaS3. PMID- 9995767 TI - Picosecond vibrational relaxation modulated by critical slowing down in ferroelectric K4Fe(CN)6 PMID- 9995768 TI - Interfacial stiffening of Cu, Ni, and Ag thin films on the Ru(0001) surface. PMID- 9995769 TI - Applicability of the Rayleigh hypothesis to real materials. PMID- 9995770 TI - Further evidence for the coexistence of localized and extended states in atomically and electronically disordered solids. PMID- 9995771 TI - Transport and microwave properties of the metal-spine conductor Co(phthalocyaninato)I. PMID- 9995772 TI - Surface-plasmon spectrum of Ag(001) measured by high-resolution angle-resolved electron-energy-loss spectroscopy. PMID- 9995773 TI - Femtosecond carrier dynamics in graphite. PMID- 9995774 TI - Analysis of the reconstructed Ir(110) surface from time-of-flight scattering and recoiling spectrometry. PMID- 9995775 TI - Mean-square displacements of surface atoms: c(2 x 2) overlayers on Ni(100). PMID- 9995776 TI - Ferromagnetic properties of Pd monolayers. PMID- 9995777 TI - Interface formation with ions and neutral atoms. PMID- 9995778 TI - Electronic and optical properties of a superlattice in a parabolic potential. PMID- 9995779 TI - Radiative recombination processes of the many-body states in multiple quantum wells. PMID- 9995780 TI - Metal-semiconductor interfaces: Magnetic and electronic properties and Schottky barrier in Fen/(ZnSe)m (001) superlattices. PMID- 9995781 TI - Computer simulation studies of the growth of strained layers by molecular-beam epitaxy. PMID- 9995783 TI - Pressure dependence of photoluminescence in InxGa1-xAs/GaAs strained quantum wells. PMID- 9995782 TI - Elastic properties of GaAs/AlAs superlattices. PMID- 9995784 TI - Temperature dependence of the direct energy gap in a GaAs/AlAs superlattice. PMID- 9995785 TI - Ga 3d excitons at surfaces and interfaces. PMID- 9995786 TI - Localization of two-dimensional exciton polaritons. PMID- 9995788 TI - Optical properties of Wannier excitons in the linear and weakly nonlinear regime. PMID- 9995787 TI - Tilted-magnetic-field measurements of activation energies and cyclotron resonance for AlxGa1-xAs-GaAs heterojunctions. PMID- 9995789 TI - Phonon-mediated excitonic optical bistability in polymers. PMID- 9995790 TI - Electronic properties of nascent GaP(110)-noble-metal interfaces. PMID- 9995791 TI - Partial densities of states for silver bromide and silver iodobromide. PMID- 9995792 TI - Subnanosecond transient photoconductivity in poly(3-hexylthiophene). PMID- 9995793 TI - Picosecond photoinduced absorption and polarization memory in polythiophene derivatives. PMID- 9995795 TI - Evolution of the electronic states of coupled (In,Ga)As-GaAs quantum wells into superlattice minibands. PMID- 9995794 TI - Morphology and barrier-height development of Bi/InP(110) interfaces. PMID- 9995797 TI - Al 2p core exciton in AlxGa1-xAs. PMID- 9995796 TI - Band offsets in pseudomorphically grown Si/Si1-xGex heterostructures studied with core-level x-ray photoelectron spectroscopy. PMID- 9995798 TI - Calculations of the electronic structure of highly strained GaAs/GaSb/GaAs heterostructures. PMID- 9995800 TI - Influence of film and deposition parameters on the electrical conduction in CdSexTe1-x thin films. PMID- 9995799 TI - Theoretical study of muon-induced solitons in polyacetylene. PMID- 9995801 TI - Electronic structure of an InAs monomolecular plane in GaAs. PMID- 9995803 TI - Phonon-assisted cyclotron resonance in n-type quantum-well structures. PMID- 9995802 TI - Excitation mechanisms of photoluminescence in double-barrier resonant-tunneling structures. PMID- 9995805 TI - Probability-density-function description of mesoscopic normal tunnel junctions. PMID- 9995804 TI - Raman scattering in a superlattice under an electric field. PMID- 9995806 TI - Comparison and spatial profiling of strain in PMID- 9995807 TI - Strain-induced quantum confinement of carriers due to extended defects in silicon. PMID- 9995809 TI - Impurity incorporation and doping efficiency in a-Si:H. PMID- 9995808 TI - Hydrostatic pressure coefficients of the photoluminescence of InxGa1-xAs/GaAs strained-layer quantum wells. PMID- 9995810 TI - Polarizabilities of shallow donors in quantum wells. PMID- 9995811 TI - Polarizabilities of shallow donors in finite-barrier quantum wells. PMID- 9995812 TI - Cell-cluster and self-consistent calculations for a model sodium chloride crystal. PMID- 9995813 TI - EPR study of hole trapping at cation vacancies in silver halides. PMID- 9995814 TI - X-ray-diffraction study of the crystal structures and orientational glass state of Ar1-x(N2)x solid solutions. PMID- 9995815 TI - Raman scattering from VO2 single crystals: A study of the effects of surface oxidation. PMID- 9995816 TI - Generalized renormalization-group calculation of x-ray photoemission spectra for a simple metal. PMID- 9995817 TI - Depolarization and metallization in alkali-metal overlayers. PMID- 9995818 TI - Vibrational frequencies of Si-P-H complexes in crystalline silicon: A theoretical study. PMID- 9995819 TI - Observation of a metallic impurity band in n-type GaAs. PMID- 9995821 TI - Stress-induced switching of nonlinear optical properties of linear polymers. PMID- 9995820 TI - Proximity effect in the collective excitations of the fractional quantum Hall state. PMID- 9995822 TI - Temperature and volume dependence of the Raman spectrum of ammonia solid II. PMID- 9995823 TI - Erratum: Small-crystal approach to ordered semiconductor compounds PMID- 9995824 TI - Erratum: Surface reconstructions of GaAs(100) observed by scanning tunneling microscopy PMID- 9995825 TI - Erratum: Effective-mass approximation in semiconductor heterostructures: One dimensional analysis PMID- 9995826 TI - Magnetoresistance of very pure simple metals. PMID- 9995827 TI - Simulated annealing of carbon clusters. PMID- 9995828 TI - Local-spin-density calculations for iron: Effect of spin interpolation on ground state properties. PMID- 9995829 TI - Exciton localization in submonolayer InAs/GaAs multiple quantum wells. PMID- 9995831 TI - Possible observation of impurity effects on conductance quantization. PMID- 9995830 TI - Stability and band offsets of heterovalent superlattices: Si/GaP, Ge/GaAs, and Si/GaAs. PMID- 9995832 TI - Interface-roughness-controlled exciton mobilities in GaAs/ Al0.37Ga0.63As quantum wells. PMID- 9995834 TI - Synchrotron-radiation-induced surface photovoltage on GaAs studied by contact potential-difference measurements. PMID- 9995833 TI - Fractional quantum Hall effect in a two-dimensional electron-hole fluid. PMID- 9995835 TI - Adsorption and interaction of Sm on GaAs(110) studied by scanning tunneling microscopy. PMID- 9995836 TI - Resonant-Raman-scattering studies of disorder in solution-cast polydiacetylene films. PMID- 9995837 TI - Photoabsorption of small metal clusters: Surface and volume modes. PMID- 9995838 TI - Segregation at the Pt0.5Ni0.5(111) surface studied by medium-energy ion scattering. PMID- 9995840 TI - Experimental demonstration of the role of local latent heat in Ge pattern formation. PMID- 9995839 TI - Theory of the effects of destruction of localization by inelastic scattering in the resistivity of pure thin potassium wires. PMID- 9995842 TI - Structural and electronic properties of Rh overlayers on Mo(110). PMID- 9995841 TI - Accurate forces in a local-orbital approach to the local-density approximation. PMID- 9995843 TI - Switching of K0.3MoO3 at low temperatures. I. Response to the dc electric field. PMID- 9995844 TI - Switching of K0.3MoO3 at low temperatures. II. ac conductivity in the highly conducting state. PMID- 9995845 TI - Temperature dependence of the optical conductivity of the heavy-fermion system CeCu6. PMID- 9995846 TI - Structure and vibrations of chemically produced Au55 clusters. PMID- 9995847 TI - Optical-absorption spectra, crystal-field energy levels, and transition line strengths of holmium in trigonal Na3 PMID- 9995848 TI - Parametric analysis of f-f transition intensities in trigonal Na3 PMID- 9995849 TI - Universal stabilizing mechanism for transition-metal polytetrahedrally packed phases. PMID- 9995850 TI - Coupled-cluster approaches with an approximate account of triexcitations and the optimized-inner-projection technique. II. Coupled-cluster results for cyclic polyene model systems. PMID- 9995851 TI - Electrical-conduction mechanisms in polymer-copper-particle composites. I. Temperature and high-magnetic-field dependence of the conductivity. PMID- 9995852 TI - Electrical-conduction mechanisms in polymer-copper-particle composites. II. (1/f) noise measurements in the percolation limit. PMID- 9995853 TI - Molecular-dynamics study of liquid NaPb, KPb, RbPb, and CsPb alloys. PMID- 9995854 TI - Change in resistivity of simple metals on melting. PMID- 9995855 TI - Termination and rumpling of nonunique surfaces. PMID- 9995856 TI - Numerical studies of femtosecond carrier dynamics in GaAs. PMID- 9995858 TI - Dissociation kinetics of hydrogen-passivated (111) Si-SiO2 interface defects. PMID- 9995857 TI - Reflectance study of interwell couplings in GaAs-Ga1-xAlxAs double quantum wells. PMID- 9995859 TI - Resonant-acceptor-bound magnetic polarons in the zero-band-gap semimagnetic semiconductor Hg1-xMnxTe. PMID- 9995860 TI - EPR evidence for As interstitial-related defects in semi-insulating GaAs. PMID- 9995861 TI - Local-density theory of band offsets in strained superlattices: (InAs)n/(InP)n (001). PMID- 9995862 TI - Strong chemical reactivity at the early stages of Yb overgrowth on GaP(110): A synchrotron-radiation study. PMID- 9995863 TI - Operator ordering in effective-mass theory for heterostructures. I. Comparison with exact results for superlattices, quantum wells, and localized potentials. PMID- 9995864 TI - Operator ordering in effective-mass theory for heterostructures. II. Strained systems. PMID- 9995865 TI - Variational quantum Monte Carlo nonlocal pseudopotential approach to solids: Formulation and application to diamond, graphite, and silicon. PMID- 9995866 TI - Conductance oscillations periodic in the density of one-dimensional electron gases. PMID- 9995867 TI - Analytical properties of a (Wannier) exciton-phonon system: On the exclusion of self-trapping and overscreening. PMID- 9995868 TI - Influence of substrate composition and crystallographic orientation on the band structure of pseudomorphic Si-Ge alloy films. PMID- 9995869 TI - One-electron formalism for second-harmonic generation in crystalline semiconductors. PMID- 9995870 TI - Anomalous Hall-effect results in low-temperature molecular-beam-epitaxial GaAs: Hopping in a dense EL2-like band. PMID- 9995871 TI - Spatial distribution of the wave functions of a graphite surface studied by use of metastable-atom electron spectroscopy. PMID- 9995873 TI - Wannier-Stark localization of X and Gamma states in GaAs-AlAs short-period superlattices. PMID- 9995872 TI - Electronic transitions in CdTe under pressure. PMID- 9995874 TI - Electromodulation spectroscopy of metalorganic-vapor-phase-epitaxy-grown GaAs/AlxGa1-xAs multiple quantum wells. PMID- 9995876 TI - Electron-hole recombination in narrow-band-gap Hg1-xCdxTe and stimulated emission of LO phonons. PMID- 9995875 TI - Stimulated emission of LO phonons in narrow-band-gap semiconductors. PMID- 9995877 TI - Deep europium-bound exciton in a ZnS lattice. PMID- 9995878 TI - Core excitons and conduction-band structures in orthorhombic GeS, GeSe, SnS, and SnSe single crystals. PMID- 9995879 TI - Structural complexity in grain boundaries with covalent bonding. PMID- 9995880 TI - Tetrahedron model for the optical dielectric function of hydrogenated amorphous silicon nitride alloys. PMID- 9995881 TI - Optical dielectric function and infrared absorption of hydrogenated amorphous silicon nitride films: Experimental results and effective-medium-approximation analysis. PMID- 9995882 TI - Second-harmonic generation in a Fibonacci optical superlattice and the dispersive effect of the refractive index. PMID- 9995884 TI - Analytical formalism for determining quantum-wire and quantum-dot band structure in the multiband envelope-function approximation. PMID- 9995883 TI - Transmission of light through deterministic aperiodic non-Fibonaccian multilayers. PMID- 9995885 TI - Single-crystal neutron-diffraction study of the orientational glass state of (NaCN)1-x(KCN)x. PMID- 9995887 TI - Temperature dependence of the low-temperature mobility in ultrapure AlxGa1 xAs/GaAs heterojunctions: Acoustic-phonon scattering. PMID- 9995886 TI - Low-symmetry effects in optical absorption of doped Tutton-salt crystals. PMID- 9995889 TI - Physisorption of CO and N2 on Al(111): Observation of surface-molecule vibrations in electron resonance scattering. PMID- 9995888 TI - Helical electromagnetic solitons in metals. PMID- 9995890 TI - Surface stability of ordered lattice-mismatched III-V alloys. PMID- 9995892 TI - Kinetics study of the GaP(110)/Cu interface via P L2,3VV Auger line shape and x ray-photoemission spectroscopies. PMID- 9995891 TI - Evidence for the influence of electron-electron interaction on the chemical potential of the two-dimensional electron gas. PMID- 9995894 TI - Nonlinear transport in ballistic quantum chains. PMID- 9995893 TI - Microscopic theory of enhanced nonlinear refraction in semiconductor superlattices. PMID- 9995895 TI - Electronic structure of random Al0.5Ga0.5As alloys: Test of the "special quasirandom-structures" description. PMID- 9995896 TI - Successive oxidation stages of adatoms on the Si(111)7 x 7 surface observed with scanning tunneling microscopy and spectroscopy. PMID- 9995897 TI - Observation of dipolar interactions between Pb0 defects at the (111) Si/SiO2 interface. PMID- 9995898 TI - Room-temperature nitridation of gallium arsenide using alkali metal and molecular nitrogen. PMID- 9995899 TI - Excited-state absorption by Eu2+ in NaF and KMgF3. PMID- 9995900 TI - Optical-pumping effects on Raman-heterodyne-detected multipulse rf nuclear-spin echo decay. PMID- 9995902 TI - Electron-spin-resonance and optical study of the Bi0(6p3) center in KCl. PMID- 9995901 TI - Multiple-scattering Green-function method for electronic-structure calculations of surfaces and coherent interfaces. PMID- 9995903 TI - Four-wave-mixing spectroscopy of Cr-doped garnet crystals. PMID- 9995904 TI - Total electron yield of layered synthetic materials with interfacial roughness. PMID- 9995905 TI - Computer simulations on collision-sequence mechanisms: Bombardment of single crystalline Cu(100) by Ar ions. PMID- 9995906 TI - Computer simulations on sputtering mechanisms: Bombardment of single-crystalline Cu(100) by Ar ions. PMID- 9995908 TI - Stopping powers of 7Li, 11B, 12C, 14N, and 16O ions in C16H14O3 polycarbonate. PMID- 9995907 TI - Ground-state multiplet of rare-earth 3+ ions in R2Fe14B investigated by inelastic neutron scattering. PMID- 9995909 TI - 85Rb, 87Rb, and 17O nuclear-quadrupole-resonance study of Rb(H1-xDx)2PO4. PMID- 9995910 TI - Theory of vibrational, rotational, and phonon inelastic collisions of a triatomic molecule by a crystal surface. I. A quantum-mechanical treatment of the scattering dynamics. PMID- 9995911 TI - Theory of vibrational, rotational, and phonon inelastic collisions of a triatomic molecule by a crystal surface. II. Approximate methods and applications to resonance and adsorption. PMID- 9995912 TI - Exchange-interaction constant of polycrystalline CdCr2Se4 thin films doped with In. PMID- 9995913 TI - Two-band Hamiltonian for CuO2 planes. PMID- 9995914 TI - Simultaneous competition and coexistence between charge-density waves and reentrant superconductivity in the pressure-temperature phase diagram of the molecular conductor TTF PMID- 9995915 TI - Influence of oxygen nonstoichiometry on structure and magnetism in Pr2NiO4+ delta. PMID- 9995916 TI - Proximity effect in zero field with the Landau-Ginzburg equation. I. PMID- 9995917 TI - Proximity effect in zero field with the Landau-Ginzburg equation. II. PMID- 9995918 TI - Quasi-two-dimensional imperfect Bose gas adsorbed on a surface. PMID- 9995920 TI - Direct investigations of the superconducting surface sheath and nonlocal electrodynamics by polarized neutron reflections. PMID- 9995919 TI - Comparison of mean-field theories of an extended Hubbard model. PMID- 9995921 TI - Bound electron pairs in the presence of charge confinement. PMID- 9995922 TI - Anomalous current-voltage characteristics due to macroscopic resonant tunneling in a small Josephson junction. PMID- 9995923 TI - Andreev scattering of quasiparticle wave packets and current-voltage characteristics of superconducting metallic weak links. PMID- 9995925 TI - Effective Lagrangian for a system of nonrelativistic fermions in 2+1 dimensions coupled to an electromagnetic field: Application to anyonic superconductors. PMID- 9995924 TI - Superfluid kinetic equation approach to the dynamics of the 3He A-B phase boundary. PMID- 9995926 TI - Temperature dependence of the spin dynamics in quantum spin liquids. PMID- 9995928 TI - Nested-Fermi-liquid theory. PMID- 9995927 TI - Far-infrared photoresponse of quasi-two-dimensional granular NbN/BN films. PMID- 9995929 TI - Charged excitations of the chiral spin liquid. PMID- 9995930 TI - Chaos in long Josephson junctions without external rf driving force. PMID- 9995931 TI - Far-infrared optical properties of tetrathiofulvalene-tetracyanoquinodimethane (TTF-TCNQ). PMID- 9995932 TI - Flux-line-cutting effects at the critical current of cylindrical type-II superconductors. PMID- 9995933 TI - Modulated structures and intergrowth in Pb-doped Bi-Sr-Ca-Cu-O superconducting oxides. PMID- 9995934 TI - Coherence length and vortex filament in the boson-fermion model of superconductivity. PMID- 9995935 TI - Ion irradiation of epitaxial YBa2Cu3O7- delta films: Effects of electronic energy loss. PMID- 9995936 TI - Pairing of charge carriers in the two-dimensional molecular crystal model. PMID- 9995938 TI - Investigation of partial superconductivity in YBa2Cu3O7 at 300 K. PMID- 9995937 TI - Electronic structure and hole-hole coupling in YBa2Cu3O7-x systems. PMID- 9995939 TI - Magnetism and superconductivity in the t-J model. PMID- 9995941 TI - Image-charge-mediated pairing in oxide superconductors. PMID- 9995940 TI - Ion channeling in (Bi1.7Pb0.3)Sr2CaCu2Ox single crystals. PMID- 9995942 TI - Angle-resolved photoemission from Nd2-xCexCuO4(001): A dispersive bandlike Fermi liquid state of Cu 3d character near the Fermi level. PMID- 9995943 TI - Calculation of nuclear quadrupole splitting in high-Tc superconductors. PMID- 9995944 TI - Mossbauer study of Fe site occupancy and its effect on Tc in YBa2(Cu1-xFex)3O6+y as a function of thermal treatments. PMID- 9995945 TI - Spin-wave-velocity renormalization in the two-dimensional S=1/2 Heisenberg antiferromagnet. PMID- 9995946 TI - Characterization of superconducting Bi2Sr2Can-1CunO4+2n phases with 57Fe Mossbauer spectroscopy. PMID- 9995947 TI - Ionic model for the stability of the Y-Ba-Cu high-temperature superconductors. PMID- 9995948 TI - Rietveld analysis of the modulated structure in the superconducting oxide Bi2(Sr,Ca)3Cu2O8+x. PMID- 9995950 TI - Theory of oxygen diffusion in the YBa2Cu3O7-x superconducting compound. PMID- 9995949 TI - Polarized Raman measurements of Y1-xPrxBa2Cu3O7. PMID- 9995951 TI - Long-range antiferromagnetic ordering in Bi2CuO4. PMID- 9995952 TI - Effects of Ce substitution and and reduction on the electronic states of Nd2 xCexCuO4-y studied by x-ray photoelectron. PMID- 9995954 TI - Correlation bag and high-Tc superconductivity. PMID- 9995953 TI - Inelastic-neutron-scattering study of the electron-phonon interaction in a superconducting La1.85Sr0.15CuO4 single crystal. PMID- 9995955 TI - Oxygen-disorder and correlation effects on the hole concentration and metal nonmetal transition in YBa2Cu3O6+x. PMID- 9995956 TI - High-pressure Raman study of one-dimensional crystals of the very polar molecule hydrogen cyanide. PMID- 9995957 TI - Theory of surface spin waves in metamagnets. PMID- 9995958 TI - Electronic properties of binary alloys through direct configurational averaging: Comparison with conventional methods. PMID- 9995959 TI - X-ray-diffraction studies of the magnetic state of thulium. PMID- 9995960 TI - Phonon effects at the metamagnetic transition in CeRu2Si2. PMID- 9995962 TI - Phonons in one-dimensional Peierls-Hubbard systems. PMID- 9995961 TI - Continuum theory of 4mm-2mm proper ferroelastic transformation under inhomogeneous stress. PMID- 9995964 TI - Measurement of electron mobility in liquid and critical argon at low electric field strengths. PMID- 9995963 TI - Dielectric function of layered materials. PMID- 9995965 TI - Transient ensemble averages in non-Newtonian flow: Symmetry and simulation. PMID- 9995966 TI - Spin dynamics and the delocalization of hole quasiparticles. PMID- 9995967 TI - Model for diffusion with interactions and trapping on realizations of the percolation model. PMID- 9995969 TI - Effect of local environment on the magnetic state of cerium in (Ce1-cGdc)Rh2. PMID- 9995968 TI - Magnetization process of a disordered phase in a mixed-bond spin-1 Ising ferromagnet. PMID- 9995970 TI - Exact solutions for even-number correlations of the square Ising model. PMID- 9995972 TI - Isolated ferromagnetic bonds in the two-dimensional spin-1/2 Heisenberg antiferromagnet. PMID- 9995971 TI - Acoustic anomaly and the Landau free energy of incommensurate K2SeO4. PMID- 9995973 TI - Magnetic Compton profiles of iron and nickel. PMID- 9995974 TI - Correction-to-scaling exponent for self-avoiding walks. PMID- 9995975 TI - n-point probability functions for a lattice model of heterogeneous media. PMID- 9995977 TI - Conductance fluctuations in weakly inhomogeneous finite-size random media. PMID- 9995976 TI - Electronic structures of FeB, Fe2B, and Fe3B compounds studied using first principles spin-polarized calculations. PMID- 9995979 TI - Theory of unstable growth. PMID- 9995978 TI - Photoacoustic measurement of the thermal properties of two-layer systems. PMID- 9995980 TI - Lifshitz-Slyozov kinetics of a nonconserved system that separates into phases of different density. PMID- 9995981 TI - Growth of order in vector spin systems and self-organized criticality. PMID- 9995982 TI - Theory of spin-dependent electron diffraction from the Fe(110) surface. PMID- 9995984 TI - Effect of the Haldane gap on quasi-one-dimensional systems. PMID- 9995983 TI - Lowest-order Landau-level mixing corrections for 4 >= nu >2 quantum Hall effect. PMID- 9995985 TI - Relativistic effects on the thermal expansion of the actinide elements. PMID- 9995987 TI - Exact-enumeration approach to tunneling in disordered systems. PMID- 9995986 TI - Electrical properties of zinc ferrites Fe3-xZnxO4 with 0 <= x<0.3. PMID- 9995989 TI - Spin-Peierls, valence-bond solid, and Neel ground states of low-dimensional quantum antiferromagnets. PMID- 9995988 TI - Martensitic transformation of Ca. PMID- 9995990 TI - Spin-glass-like behavior in Cu/Ni multilayered films. PMID- 9995991 TI - Measurements of the ac conductivity and dielectric constant in a two-dimensional lattice percolation system. PMID- 9995992 TI - Two-dimensional electrons in a strong magnetic field: A basis for single-particle states. PMID- 9995993 TI - Dense sphere packings in cylindrical Penrose tilings. PMID- 9995994 TI - Anderson localization in anisotropic random media. PMID- 9995995 TI - Dipolar magnets and glasses: Neutron-scattering, dynamical, and calorimetric studies of randomly distributed Ising spins. PMID- 9995996 TI - Valence-electron contributions to the electric-field gradient in hcp metals and at Gd nuclei in intermetallic compounds with the ThCr2Si2 structure. PMID- 9995997 TI - Hidden symmetries in the one-dimensional antiferromagnetic Heisenberg model. PMID- 9995998 TI - Spontaneous symmetry breaking in the Lieb-Mattis model of antiferromagnetism. PMID- 9996000 TI - Haldane-gap modes in the S=1 antiferromagnetic chain compound CsNiCl3. PMID- 9995999 TI - Application of the Monte Carlo coherent-anomaly method to two-dimensional lattice gas systems with further-neighbor interactions. PMID- 9996001 TI - First-principles calculations for a model Hamiltonian treatment of hybridizing light actinide compounds. PMID- 9996002 TI - Critical dynamics of unstable states. PMID- 9996003 TI - Density of states of infinite quantum systems. PMID- 9996004 TI - Thomas-Fermi theory of screening of a point-charge impurity in an insulator: Nonzero temperature. PMID- 9996005 TI - Zeeman spin-splitting-frequency renormalization in disordered interacting electronic systems. PMID- 9996006 TI - Estimation of surface energy in coherent-phase mixtures controlled by elastic strain energy. PMID- 9996007 TI - Microscopic identification of the F2+-O2- center formation in LiF:OH- PMID- 9996008 TI - Pulsed diffusing-wave spectroscopy: High resolution through nonlinear optical gating. PMID- 9996009 TI - Kosterlitz-Thouless mechanism of two-dimensional superconductivity. PMID- 9996010 TI - Thermal boundary resistance between PrNi5 and liquid 3He. PMID- 9996012 TI - Magnetic frustration in the three-band Anderson lattice model for high temperature superconductors. PMID- 9996011 TI - Optical conductivity of single crystals of La2-xSrxNiO4. PMID- 9996013 TI - X-ray-absorption studies of Nd2-xCexCuO4. PMID- 9996014 TI - Competing effects on the Tc evaluation of Tl-based oxide superconductors. PMID- 9996016 TI - Spontaneous electrostatic potential in spin-split metals. PMID- 9996015 TI - Time-dependent superconducting behavior of oxygen-deficient YBa2Cu3Ox: Possible annealing of oxygen vacancies at 300 K. PMID- 9996017 TI - Ferromagnetic-resonance study of critical exponents and transition temperatures of amorphous and icosahedral Al55Mn20Si25 alloys. PMID- 9996018 TI - Stress as an order parameter for the glass transition. PMID- 9996019 TI - Comment on "Valence-band states in Bi2(Ca,Sr,La)3Cu2O8" PMID- 9996021 TI - Optical conductivity of the Hubbard and t-J models. PMID- 9996020 TI - Reply to the "Comment on 'Valence-band states in Bi2(Ca,Sr,La)3Cu2O8.' " PMID- 9996022 TI - Phonon-mediated splitting in the optical susceptibility of polymers. PMID- 9996023 TI - Specific heat of polycrystalline Ba0.6K0.4BiO3 from 0.5 to 20 K. PMID- 9996024 TI - Phase transitions in Josephson-junction ladders in a magnetic field. PMID- 9996026 TI - Gap states in dilute-magnetic-alloy superconductors: A quantum Monte Carlo study. PMID- 9996025 TI - Ground-state properties of the S=1/2 Heisenberg antiferromagnet on a triangular lattice. PMID- 9996027 TI - Observation of lanthanum- and rare-earth-site ordering in T*-phase La2-x yRxSryCuO4 (R=Sm, Eu, Gd, Tb). PMID- 9996028 TI - Ballistic quasiparticle propagation and symmetry of the superconducting order parameter. PMID- 9996029 TI - Nonsuperconducting BaSn1-xSbxO3: The 5s-orbital analog of BaPb1-xBixO3. PMID- 9996030 TI - Spiral phases and time-reversal-violating resonating-valence-bond states of doped antiferromagnets. PMID- 9996031 TI - Evidence against hole filling by Pr in YBa2Cu3O7. PMID- 9996033 TI - Seebeck effect in the mixed state of high-Tc superconductors. PMID- 9996032 TI - Flux phases in polarized spin liquids. PMID- 9996034 TI - Mobile holes in a two-dimensional Heisenberg antiferromagnet. PMID- 9996035 TI - Microwave surface resistance and vortices in high-Tc superconductors: Observation of flux pinning and flux creep. PMID- 9996036 TI - Temperature-dependent lifetime of spin excitations in RBa2Cu3O6 (R=Eu, Y). PMID- 9996038 TI - Finite-size effects and anisotropic melting of the vortex solid in high temperature superconductors. PMID- 9996037 TI - Nonlinear electrodynamics in granular YBa2Cu3O7: Measurements and models of complex permeability. PMID- 9996039 TI - Magnetoresistance of high-Tc superconductors in the fluctuation regime. PMID- 9996040 TI - Distribution of pinning energies and the resistive transition in superconducting films. PMID- 9996041 TI - Spectral function at finite doping in the t-J model. PMID- 9996043 TI - S(q, omega ) for the S=1/2 and S=1 one-dimensional Heisenberg antiferromagnet: A quantum Monte Carlo study. PMID- 9996042 TI - Pairing by dynamic charge fluctuations in the extended Hubbard model. PMID- 9996044 TI - Hard-axis magnetization of ultrathin Ni(111) films on W(110): An experimental method to measure the magneto-optic Kerr effect in ultrahigh vacuum. PMID- 9996045 TI - Universality of continuum percolation. PMID- 9996046 TI - Structural and elastic properties of zirconium nitride-aluminum nitride multilayers. PMID- 9996047 TI - Rotational and translational self-diffusion of interacting spherical Brownian particles. PMID- 9996048 TI - Magnetoresistance and Hall effect in epitaxial Co-Au superlattices. PMID- 9996049 TI - Dielectric dispersion associated with the dc-electric-field-enforced ferroelectric phase transition in the pressure-induced antiferroelectric CsH2PO4. PMID- 9996050 TI - Replica scaling analysis of interfaces in random media. PMID- 9996051 TI - Reaction and diffusion at Cu/Al interfaces studied using glancing-angle extended x-ray-absorption fine structures. PMID- 9996052 TI - Computer simulation of intrinsic localized modes in one-dimensional and two dimensional anharmonic lattices. PMID- 9996053 TI - Phase-sensitive scanning tunneling potentiometry and the local transport field in mesoscopic systems. PMID- 9996054 TI - Wave-vector dependence of the exchange contribution to the electron-gas response functions: An analytic derivation. PMID- 9996056 TI - Exact many-body solution of the periodic-cluster t-t'-J model for cubic systems: Ground-state properties. PMID- 9996055 TI - Defect-inhibited incommensurate distortion in Ta2NiSe7. PMID- 9996057 TI - Optical study of the stoichiometry-dependent electronic structure of TiCx, VCx, and NbCx. PMID- 9996059 TI - Atomic structure and segregation in alkali-metal heteroclusters. PMID- 9996058 TI - Calculation of H-H potential energies and fusion rates in PdxH2 clusters (x=2,4). PMID- 9996060 TI - Intensity of surface-plasmon polariton energy emitted into the air side in an air/Ag-film/prism configuration. PMID- 9996061 TI - Morphological equilibration of a corrugated crystalline surface. PMID- 9996062 TI - Surface resonances on Ta(001). PMID- 9996063 TI - Temperature effects on the optical absorption of jellium clusters. PMID- 9996064 TI - Theoretical determination of work functions and adsorption energies of atoms on metal surfaces from small-cluster calculations: A local-spin-density approach. PMID- 9996065 TI - Role of forms of exchange and correlation used in generating pseudopotentials. PMID- 9996067 TI - Atomic structure and bonding in liquid GaAs from Iab-initioP molecular dynamics. PMID- 9996066 TI - Anomalous behavior of Pr ions in amorphous Pr-Fe, Pr-Co, and Pr-Ni thin films. PMID- 9996068 TI - O2/GaAs(110) interface formation at 20 K: Photon-induced reaction and desorption. PMID- 9996069 TI - X-ray-diffraction measurements from imperfect GaAs crystals: Evidence for near surface defects. PMID- 9996070 TI - Properties of the Landauer resistance of finite repeated structures. PMID- 9996071 TI - Elastic strain at pseudomorphic semiconductor heterojunctions studied by x-ray photoelectron diffraction: Ge/Si(001) and Si/Ge(001). PMID- 9996072 TI - Dispersion of nonlinear optical susceptibility of GaAs/AlxGa1-xAs multiple quantum wells in the exciton region. PMID- 9996074 TI - In situ monitoring of step arrays on vicinal silicon (100) surfaces for heteroepitaxy. PMID- 9996073 TI - Intensity of exciton luminescence in silicon in a weak magnetic field. PMID- 9996075 TI - Molecular-dynamics simulations of amorphous Si. PMID- 9996076 TI - Hot-exciton relaxation in (In,Ga)As-AlAs strained quantum wells. PMID- 9996077 TI - Carrier effects on the excitonic absorption in GaAs quantum-well structures: Phase-space filling. PMID- 9996079 TI - Optical parameters of Cd1-xFexSe and Cd1-xFexTe by means of Kramers-Kronig analysis of reflectivity data. PMID- 9996080 TI - Electron states in a GaAs quantum dot in a magnetic field. PMID- 9996078 TI - Hybridization of 3d states of photodoped Cu in amorphous GeSe2 by resonant photoemission spectroscopy. PMID- 9996081 TI - Accurate interband-Auger-recombination rates in silicon. PMID- 9996082 TI - Ga configurations in hydrogenated amorphous silicon as studied by x-ray photoemission spectroscopy. PMID- 9996083 TI - Low-energy-electron escape lengths in SiO2. PMID- 9996085 TI - Chemisorption of group-III metals on the Si(111) and Ge(111) surfaces: An ab initio study. PMID- 9996084 TI - Birefringence and Faraday effect in Cd1-xMnxSe. PMID- 9996087 TI - Exciton effects on second-order nonlinear susceptibility in a quantum well with an applied electric field. PMID- 9996086 TI - Effects of interdiffusion on the electronic properties of HgTe-CdTe superlattices. PMID- 9996088 TI - Oxidation of GaAs(110) with NO2: Infrared spectroscopy. PMID- 9996090 TI - High excited states of magnetodonors in InSb: An experimental and theoretical study. PMID- 9996089 TI - Current transport in high-barrier IrSi/Si Schottky diodes. PMID- 9996091 TI - Nonresonant magnetotunneling in asymmetric GaAs/AlAs double-barrier structures. PMID- 9996092 TI - Direct inter-conduction-subband optical absorption of thin zinc-blende-structure semiconductor rectangular wires. PMID- 9996093 TI - Elasticity and thermal expansivity of (AgI)x(AgPO3)1-x glasses. PMID- 9996094 TI - Optical properties of vanadium pentoxide determined from ellipsometry and band structure calculations. PMID- 9996095 TI - Polarization properties of quasielastic light scattering in fused-silica optical fiber. PMID- 9996096 TI - Alkali-halide cluster ions produced by laser vaporization of solids. PMID- 9996097 TI - Spin-orbit contribution to the Hall coefficient approaching the metal-insulator transition: An explanation for the critical behavior of Ge:Sb. PMID- 9996098 TI - Importance of Pauli-principle restrictions for accurate numerical evaluation of the exchange-only screening function. PMID- 9996099 TI - Thermal conductivity of the molybdenum blue bronze Rb0.3MoO3. PMID- 9996100 TI - Theoretical study of the metastability of Au22+ clusters. PMID- 9996101 TI - Mean free path of a trapped physisorbed hydrogen molecule. PMID- 9996102 TI - Localization properties of the nonbonding pi states at the Fermi level in amorphous carbon. PMID- 9996103 TI - Two-dimensional electrons near a half-filled Landau level. PMID- 9996104 TI - Random-walk simulation of the dielectric constant of a composite material. PMID- 9996106 TI - Binding energies of ground and excited states of shallow acceptors in GaAs/Ga1 xAlxAs quantum wells. PMID- 9996105 TI - Convergence of force calculations for noncrystalline Si. PMID- 9996108 TI - Analytic theory of resonant magnetotransport in ballistic quantum conductors. PMID- 9996107 TI - Monte Carlo study of liquid GaAs: Bulk and surface properties. PMID- 9996109 TI - Erratum: Structural defects in chromium-ion-implanted vitreous silica PMID- 9996110 TI - Erratum: Structural properties of ordered high-melting-temperature intermetallic alloys from first-principles total-energy calculations PMID- 9996112 TI - Molecular-dynamics investigation of cluster-beam deposition. PMID- 9996111 TI - Erratum: Electronic processes in double-barrier resonant-tunneling structures studied by photoluminescence spectroscopy in zero and finite magnetic fields PMID- 9996114 TI - Fermi-surface-driven ordering process in the Ag-Mg alloys near Ag3Mg. PMID- 9996113 TI - Nondipole channels in the electron-energy-loss structure near the 3s edge of copper. PMID- 9996115 TI - Energy and structure of uniaxial incommensurate monolayer solids: Application to Xe/Pt(111). PMID- 9996117 TI - Reconstruction and Fermi surface of W(001). PMID- 9996116 TI - Two-dimensional condensation of potassium on Ag(001). PMID- 9996119 TI - Formation of the 5 x 5 reconstruction on cleaved Si(111) surfaces studied by scanning tunneling microscopy. PMID- 9996118 TI - Structural changes in boron-doped hydrogenated amorphous silicon during long-time annealing below the deposition temperature. PMID- 9996120 TI - Room-temperature emission of highly excited GaAs/Ga1-xAlxAs quantum wells. PMID- 9996121 TI - Grazing-angle x-ray standing waves. PMID- 9996122 TI - Picosecond acoustics in polythiophene thin films. PMID- 9996123 TI - Low-temperature energy relaxation in AlxGa1-xAs/GaAs heterojunctions. PMID- 9996124 TI - Electron localization in polyaniline derivatives. PMID- 9996125 TI - Giant discrete resistance fluctuations observed in normal-metal tunnel junctions. PMID- 9996126 TI - Magnetic anisotropy in low-dimensional ferromagnetic systems: Fe monolayers on Ag(001), Au(001), and Pd(001) substrates. PMID- 9996128 TI - Electron-energy-loss cross-section and surface lattice-dynamics studies of NiAl(110). PMID- 9996127 TI - Surface-phonon dispersion of NiAl(110). PMID- 9996129 TI - 2p x-ray absorption of 3d transition-metal compounds: An atomic multiplet description including the crystal field. PMID- 9996131 TI - Tunneling characteristics of different models for the metal-vacuum-metal barrier. PMID- 9996130 TI - Far-infrared investigation of the generalized Lyddane-Sachs-Teller relation using ZnS-diamond composites. PMID- 9996132 TI - Amorphization along interfaces and grain boundaries in polycrystalline multilayers: An x-ray-diffraction study of Ni/Ti multilayers. PMID- 9996133 TI - Core structure of a dissociated easy-glide dislocation in copper investigated by molecular dynamics. PMID- 9996134 TI - Linear and nonlinear response of alkali-metal adlayers on metal surfaces to a static electric field. PMID- 9996135 TI - Calculation of the reflection coefficients of interfaces: A scattering approach. PMID- 9996136 TI - Impurity-induced grain-boundary embrittlement: A simple three-dimensional model. PMID- 9996137 TI - Magnetovolume transition in ordered Ni3Al. PMID- 9996138 TI - Nonlinear equation for diffusion and adatom interactions during epitaxial growth on vicinal surfaces. PMID- 9996139 TI - High-field magnetization of magnetic graphite intercalation compounds. PMID- 9996141 TI - Effect of finite system size on thermal fluctuations: Implications for melting. PMID- 9996140 TI - Energy shifts and broadening of atomic levels near metal surfaces. PMID- 9996142 TI - Local chiral symmetry and charge-density waves in one-dimensional conductors. PMID- 9996144 TI - Coulomb blockade on imaged mesoscopic lead grains. PMID- 9996143 TI - Surface x-ray-scattering measurements of the substrate-induced spatial modulation of an incommensurate adsorbed monolayer. PMID- 9996145 TI - Surface lattice dynamics of nearly incommensurate overlayers. PMID- 9996146 TI - Radiative decay and phonon scattering of biexcitons in CuCl. PMID- 9996147 TI - Edge states in quantum wires in high magnetic fields. PMID- 9996148 TI - Photoluminescence study of radiative channels in ion-implanted silicon. PMID- 9996150 TI - Long-distance photoassisted electron transfer. PMID- 9996149 TI - Introduction, revelation, and evolution of complementary gratings in photorefractive bismuth silicon oxide. PMID- 9996152 TI - Transport properties of vanadium germanate glassy semiconductors. PMID- 9996151 TI - Electronic band structure of GaAs sawtooth-doping superlattices. PMID- 9996153 TI - Bond densities and electronic structure of amorphous SiNx:H. PMID- 9996155 TI - Site determination of oxygen in B6O by oxygen K alpha x-ray-emission spectroscopy. PMID- 9996154 TI - Monte Carlo simulation of electron-hole thermalization in photoexcited bulk semiconductors. PMID- 9996156 TI - Monte Carlo method for the simulation of electronic noise in semiconductors. PMID- 9996157 TI - Shear-deformation-potential constant of the conduction-band minima of Si: Pseudopotential calculations. PMID- 9996158 TI - Dynamics of resonant and nonresonant electron tunneling in double-quantum-well structures under electric fields. PMID- 9996159 TI - Electronic structure of Si(111)-NiSi2(111) A-type and B-type interfaces. PMID- 9996160 TI - Magneto-optics in GaAs-AlxGa1-xAs single heterojunctions. PMID- 9996161 TI - Influence of stacking faults in polymorphic ZnS on the d5 crystal-field states of Mn2+ PMID- 9996162 TI - EPR identification of the single-acceptor state of interstitial carbon in silicon. PMID- 9996163 TI - Bistable interstitial-carbon-substitutional-carbon pair in silicon. PMID- 9996164 TI - H2S+S: A model system for a sulfur-based charge-transfer salt. PMID- 9996165 TI - Point-defect equilibrium during diffusion of purely substitutional impurities into elemental crystals. PMID- 9996166 TI - Raman scattering by the coupled plasmon-LO-phonon modes near the E0+ Delta 0 gap of n-type GaAs: Resonance and interference effects. PMID- 9996167 TI - Experimental study of the Gamma -X electron transfer in type-II (Al,Ga)As/AlAs superlattices and multiple-quantum-well structures. PMID- 9996168 TI - Anisotropic thermal conductivity in mercurous chloride crystals. PMID- 9996170 TI - Tunneling states in neutron-irradiated quartz: Measurements of the ultrasonic attenuation and velocity change. PMID- 9996169 TI - Stimulated Raman scattering in lithium formate monohydrate crystals at temperatures from 2 to 300 K. PMID- 9996171 TI - Relaxation of persistent photoconductivity in Al0.3Ga0.7As. PMID- 9996173 TI - Microscopic approach to the structure of transition-metal glasses. PMID- 9996172 TI - Temperature dependence of the resistivity in Cu/Ti superlattices. PMID- 9996174 TI - Conductance of Fabry-Perot and two-slit electronic waveguides. PMID- 9996175 TI - Bremsstrahlung-isochromat-spectroscopy and x-ray-photoelectron-spectroscopy investigation of the electronic structure of beta -FeSi2 and the Fe/Si(111) interface. PMID- 9996176 TI - Lattice dynamics of Si/Ge (001) superlattices. PMID- 9996177 TI - Stark-ladder behavior of the X levels in a type-II GaAs/AlAs superlattice measured using electroreflectance spectroscopy. PMID- 9996178 TI - Volume dependence of ion polarizabilities in alkali-halide crystals. PMID- 9996179 TI - Relaxation kinetics in hydrogenated amorphous silicon. PMID- 9996181 TI - Coulomb blockade of resonant tunneling. PMID- 9996180 TI - Magnetic-field-induced type-I-->type-II transition in a semimagnetic CdTe/Cd0.93Mn0.07Te superlattice. PMID- 9996182 TI - Thermomagnetic transport coefficients of a periodically modulated two-dimensional electron gas. PMID- 9996183 TI - Explicit evidence for bipolaron formation: Cs-doped biphenyl. PMID- 9996184 TI - Image charges in semiconductor quantum wells: Effect on exciton binding energy. PMID- 9996185 TI - Deuteron relaxation in HD-n-D2 mixtures. PMID- 9996186 TI - Two-photon spectroscopy of MgO:Ni2+ PMID- 9996187 TI - Photoionization yields in the doubly doped SrF2:Eu,Sm system. PMID- 9996188 TI - Azimuthal-angle and energy distributions of Al2+ ejected from Al(100) by Ar+ bombardment. PMID- 9996189 TI - Infrared spectroscopic study of the dressed rotations of CN- isotopes in alkali halide crystals. PMID- 9996190 TI - Radiative electron capture by channeled ions. PMID- 9996191 TI - Photorefractive properties of KNbO3. PMID- 9996192 TI - Coexisting static magnetic order and superconductivity in CeCu2Si2 found by nuclear quadrupole resonance. PMID- 9996193 TI - 39K NMR study of the paraelectric-to-incommensurate phase transition in K2ZnCl4. PMID- 9996194 TI - High-resolution optical study of a point-contact-induced phonon hot spot in ruby. PMID- 9996196 TI - Pressure dependence of electronic densities of states and superconducting transition temperatures in NiZr glasses. PMID- 9996195 TI - Anisotropic specific-heat behavior under a magnetic field of a YBa2Cu3O7 single crystal. PMID- 9996197 TI - Doping dependence of high-energy spectral weights for the high-Tc cuprates. PMID- 9996199 TI - Superconductivity and dissipation in small-diameter Pb-In wires. PMID- 9996198 TI - Thermal fluctuations, quenched disorder, phase transitions, and transport in type II superconductors. PMID- 9996201 TI - Layered perovskite compounds Srn+1VnO3n+1 (n=1, 2, 3, and PMID- 9996200 TI - Charge-density wave with imperfect nesting and superconductivity. II. PMID- 9996202 TI - Quantum spin-liquid state with a hole. PMID- 9996203 TI - Geometric interpretation of the weak-field Hall conductivity in two-dimensional metals with arbitrary Fermi surface. PMID- 9996204 TI - Macroscopic effects of local oxygen fluctuations in YBa2Cu3O6+x. PMID- 9996205 TI - Modulation corrections to the modulated microwave absorption of a pure mercury sample. PMID- 9996206 TI - Deviations from the impulse approximation in liquid 4He: An experimental test at Q=23 A -1. PMID- 9996207 TI - Resonant tunneling in small current-biased Josephson junctions. PMID- 9996208 TI - Heat capacity of single-crystal La2CuO4 and polycrystalline La2-xSrxCuO4 (0 <= x <= 0.20) from 110 to 600 K. PMID- 9996209 TI - Cu and O NMR studies of the magnetic properties of YBa2Cu3O6.63 (Tc=62 K). PMID- 9996210 TI - Application of the antiferromagnetic-Fermi-liquid theory to NMR experiments on YBa2Cu3O6.63. PMID- 9996211 TI - Application of antiferromagnetic-Fermi-liquid theory to NMR experiments in La1.85Sr0.15CuO4. PMID- 9996212 TI - Superconductivity in a very high magnetic field. PMID- 9996213 TI - Upper critical magnetic field of the heavy-electron superconductors U1-xThxBe13 (x=0 and 2.9%) doped with paramagnetic Gd and other rare-earth ions. PMID- 9996214 TI - Quantum mechanics of the fractional-statistics gas: Particle-hole interaction. PMID- 9996215 TI - Kondo resonance in the neutron spectra of intermediate-valent YbAl3. PMID- 9996216 TI - Collective oscillations of twin boundaries in high-temperature superconductors as an acoustic analogue of two-dimensional plasmons. PMID- 9996217 TI - Electronic structure studies on the n-type doped superconductors R2-xMxCuO4- delta (R=Pr,Nd,Sm; M=Ce,Th) and Nd2CuO4-xFx by electron-energy-loss spectroscopy. PMID- 9996218 TI - Charge-fluctuation effect on the critical temperature of layered high-Tc superconductors. PMID- 9996219 TI - Core-level changes induced by oxygen in YBa2Cu3O7- delta. PMID- 9996220 TI - Two-component superconductivity. I. Introduction and phenomenology. PMID- 9996221 TI - Positron annihilation from nearly localized Fermi liquids: A probe of pairing. PMID- 9996222 TI - Theoretical calculation of the wave-vector- and frequency-dependent dielectric function of YBa2Cu3O7. PMID- 9996224 TI - Calculations of the dimensional dependence of the critical state in disk-shaped superconductors. PMID- 9996223 TI - Frequency and magnetic-field dependence of the dielectric constant and conductivity of La2CuO4+y. PMID- 9996225 TI - Thermal-conductivity anisotropy of single-crystal Bi2Sr2CaCu2O8. PMID- 9996226 TI - Exact solution of the London equation in two dimensions. PMID- 9996227 TI - Raman spectra of bismuth cuprate high-Tc superconductors and 3d-metal-substituted phases. PMID- 9996228 TI - Hole superconductivity in oxides: A two-band model. PMID- 9996230 TI - Resistance measurements and oxygen out-diffusion near the orthorhombic-tetragonal phase transformation in single-crystal YBa2Cu3O7- delta. PMID- 9996229 TI - Photoelectron spectroscopic study of Ba1-xRbxBiO3. PMID- 9996231 TI - Magnetic and structural study of La1.8Sr0.2NiO4. PMID- 9996232 TI - Magnetic properties and superconducting-fluctuation diamagnetism above Tc in Bi2 xPbxSr2CaCu2O8+ delta (x=0.0, 0.1, 0.2, 0.3, 0.5) and Bi2-xPbxSr2Ca2Cu3O10+ delta (x=0.2, 0.25). PMID- 9996233 TI - Heat capacity of high-purity polycrystalline YBa2Cu3O7 from 0.4 to 400 K in applied magnetic fields of 0 and 70 kG. PMID- 9996234 TI - Optical conductivity in high-Tc superconductors. PMID- 9996235 TI - Monte Carlo simulations of resonating-valence-bond U(1) dynamics. PMID- 9996236 TI - Cohesion energy and structural phase stability in La2CuO4: The orthorhombic state. PMID- 9996238 TI - Thermally activated dissipation in a long-term-annealed single crystal of Bi2Sr2CaCu2Ox. PMID- 9996237 TI - Ultrasonic investigation of granular superconducting films. PMID- 9996239 TI - Electronic structure of YBa2(Cu1-xNix)3O7 in terms of the real-space-scattering coherent-potential approximation. PMID- 9996240 TI - High-frequency vortex dynamics and dissipation of high-temperature superconductors. PMID- 9996241 TI - Origin of electric-field gradients in high-temperature superconductors: YBa2Cu3O7. PMID- 9996242 TI - Ground state of the atomic structure of YBa2Cu3O6+x. PMID- 9996243 TI - Optical study of the doping effect in the metallic oxide (Nd,Sr)CoO3. PMID- 9996244 TI - Model based on single-ion theory: Preferential substitution at different rare earth sites in quasiternary (Nd,Pr)2Fe14B compounds. PMID- 9996245 TI - Spinless fermions on frustrated lattices in a magnetic field. PMID- 9996246 TI - 39K NMR study of the antiferroelectric phase transition in potassium thiocyanate. PMID- 9996247 TI - Longitudinal spin fluctuations in nickel. PMID- 9996248 TI - Continuous cooling of a one-dimensional bonded fluid: A Monte Carlo simulation study. PMID- 9996249 TI - Phenomenology and corrections to scaling in Heisenberg ferromagnets. PMID- 9996250 TI - Correlation functions for the two-dimensional Hubbard model. PMID- 9996252 TI - Phase modulation and far-field spatial patterns due to the transformational thermal-lens effect. PMID- 9996251 TI - Effect of correlations and disorder on electron states in the Mott-Hubbard insulator V2O3. PMID- 9996253 TI - Energetics of point defects in the two-dimensional Wigner crystal. PMID- 9996255 TI - Ferroelastic phase transition in K3Na(CrO4)2: Brillouin scattering studies and theoretical modeling. PMID- 9996254 TI - Growth kinetics and domain morphology after off-critical quenches in a two dimensional fluid model. PMID- 9996257 TI - Order-parameter vibrations in the NbTe4 charge-density-wave system. PMID- 9996256 TI - Cation distribution and magnetic properties of titanomagnetites Fe3-xTixO4 (0 <= x<1). PMID- 9996258 TI - Scale-invariant disorder in fracture and related breakdown phenomena. PMID- 9996259 TI - Magnetic structures and excitations of CsMnI3: A one-dimensional Heisenberg antiferromagnet with easy-axis anisotropy. PMID- 9996260 TI - Calorimetric study of the magnetic order in Ho(Co1-xRhx)2 alloys. PMID- 9996261 TI - "2+4" model: A Monte Carlo study. PMID- 9996262 TI - Metallic ferromagnetism in a single-band model. IV. Effect of pair hopping. PMID- 9996263 TI - Magnetoelastic dissipation in macroscopic magnetization tunneling. PMID- 9996264 TI - Resonating-valence-bond theory for the square-planar lattice. PMID- 9996266 TI - Magnetization and neutron-diffraction studies of magnetic properties of single crystal DyMn2Ge2. PMID- 9996265 TI - Topological long-range order for resonating-valence-bond structures. PMID- 9996267 TI - Path-integral Monte Carlo study of the hard-disk solid. PMID- 9996268 TI - Percolation properties of the Wolff clusters in planar triangular spin models. PMID- 9996270 TI - Diffusive behavior of states in the Hubbard-Stratonovitch transformation. PMID- 9996269 TI - Theory of the phase-transition sequence in betaine calcium chloride dihydrate (BCCD). PMID- 9996271 TI - Giant monolayer magnetization of Fe on MgO: A nearly ideal two-dimensional magnetic system. PMID- 9996272 TI - Local-chemical-potential approach to small-cluster many-body systems. PMID- 9996273 TI - Two-soliton excitations and spin-wave responses in the antiferromagnets CsCoBr3 and CsCoCl3. PMID- 9996275 TI - Two-magnon states of the alternating-bond ferrimagnetic chain. PMID- 9996274 TI - Fluid configurations in partially saturated porous media. PMID- 9996277 TI - Renormalized field theory for the static crossover in isotropic dipolar ferromagnets. PMID- 9996276 TI - Magnetic and metal-insulator transitions in metallic hydrogen. PMID- 9996278 TI - Synchrotron x-ray study of dimensional crossover in solid-phase smectic liquid crystal films. PMID- 9996279 TI - Nonexponential relaxation of diluted antiferromagnets. PMID- 9996280 TI - Theory of x-ray-absorption spectra in PrO2 and some other rare-earth compounds. PMID- 9996281 TI - Strong carrier scattering by a Cu2+ local moment array in one-dimensional molecular conductors CuxNi1-x(phthalocyaninato)I. PMID- 9996282 TI - Mean-field approach to magnetic ordering in highly frustrated pyrochlores. PMID- 9996283 TI - Theoretical analysis of R-line shifts of ruby subjected to different deformation conditions. PMID- 9996284 TI - Magnetic properties of Al-Ge-Mn and Al-Cu-Ge-Mn icosahedral alloys. PMID- 9996285 TI - Transfer-matrix cluster approximation for lattice models. PMID- 9996286 TI - Simple model of kinetic roughening of quasicrystalline surfaces. PMID- 9996287 TI - Six-dimensional structure model for the icosahedral quasicrystal Al6CuLi3. PMID- 9996288 TI - Melting of monolayer argon adsorbed on a graphite substrate. PMID- 9996289 TI - Theoretical study of the structural stability of CuPd and CuPt alloys: Pressure induced phase transition of CuPt alloy. PMID- 9996290 TI - Domain-growth kinetics and aspects of pinning: A Monte Carlo simulation study. PMID- 9996292 TI - Dynamics of droplets in random Ising magnetic systems. PMID- 9996291 TI - Linear magnetic birefringence measurements of Faraday materials. PMID- 9996293 TI - Cell geometry for cluster-based quasicrystal models. PMID- 9996294 TI - Twin bands in martensites: Statics and dynamics. PMID- 9996295 TI - Generalized Thue-Morse chains and their physical properties. PMID- 9996296 TI - Monte Carlo study of the surface special transition in the XY model in three dimensions. PMID- 9996297 TI - Quadratic substrate energy term and harmonics in the Halperin-Nelson model. PMID- 9996298 TI - Nonlinear dynamics of the Frenkel-Kontorova model with impurities. PMID- 9996300 TI - Anharmonic perturbation theory for the lattice-dynamic shell model. PMID- 9996299 TI - Exchange interactions and magnetic dimension in Cu(L-alanine)2. PMID- 9996301 TI - Exact solution of the one-dimensional fermion system on a lattice. PMID- 9996302 TI - Creation of sine-Gordon solitons by a pulse force. PMID- 9996303 TI - Branching rules of the energy spectrum of one-dimensional quasicrystals. PMID- 9996304 TI - Critical behavior of a model band ferromagnet. PMID- 9996305 TI - Effective gauge interaction in a fractional-statistical gas. PMID- 9996306 TI - Fast luminescence observed in MnF2 crystals. PMID- 9996307 TI - Highly asymmetric electric-field gradients at the Nb sites in ferroelastic GdNbO4 and NdNbO4. PMID- 9996308 TI - High-energy-neutron spectroscopy of crystal-field excitations in NpO2. PMID- 9996309 TI - Analytic solution for the current-voltage characteristic of two mesoscopic tunnel junctions coupled in series. PMID- 9996310 TI - Quenched-impurity and magnetic-field effects on the phase transition in unconventional superconductors. PMID- 9996311 TI - Magnetic rare-earth contributions to muon relaxation rates and frequency shifts in RBa2Cu3O7- delta. PMID- 9996313 TI - Intrinsic variation of the intergrain critical current in polycrystalline YBa2Cu3O7-x. PMID- 9996312 TI - Penetration depth in phenomenological marginal-Fermi-liquid model for CuO. PMID- 9996314 TI - Effects of Ce and F substitutions on the electronic structure of Nd2CuO4 superconductors. PMID- 9996316 TI - Numerical determination of the order of phase transitions in Ising systems with multispin interactions. PMID- 9996315 TI - Optical study of plasmons in Tl2Ba2Ca2Cu3O10. PMID- 9996317 TI - Gutzwiller wave-function description of a particle in a fermionic bath. PMID- 9996318 TI - X-ray dichroism as a probe of the electronic ground state in ultrathin rare-earth overlayers. PMID- 9996319 TI - Hopping conductivity of the Fibonacci-chain quasicrystal. PMID- 9996320 TI - Ferromagnetic-resonance spectrum of exchange-coupled ferromagnetic bilayers. PMID- 9996321 TI - Cyclotron resonance in a Wigner crystal: A mean-field approach. PMID- 9996322 TI - Intermediate-range order in permanently densified vitreous SiO2: A neutron diffraction and molecular-dynamics study. PMID- 9996324 TI - Quantum studies of the two-dimensional axial next-nearest-neighbor Ising model: A BCS-type theory. PMID- 9996323 TI - Metastability in slow thin-film reactions. PMID- 9996326 TI - Erratum: Repulsion-induced superconductivity in a multiband Hubbard model PMID- 9996325 TI - Transport coefficients of dilute magnetic alloys: A quantum Monte Carlo study. PMID- 9996327 TI - Erratum: Van Hove correlation functions for identical fermions: Effects of interactions PMID- 9996329 TI - Photoelectron spectroscopy towards the meV range: Observation of the superconducting transition in Nb3Al. PMID- 9996328 TI - Excitations in the mixed state of type-II superconductors. PMID- 9996330 TI - Hall coefficient of the doped Mott insulator: A signature of parity violation. PMID- 9996331 TI - Relaxation of nuclear spin due to long-range orbital currents. PMID- 9996332 TI - Coexistence of Bose-Einstein paraexcitons with Maxwell-Boltzmann orthoexcitons in Cu2O. PMID- 9996333 TI - Magnetic and electrical properties of La2-xSrxNiO4+/- delta. PMID- 9996335 TI - Specific heat in the mixed state of superconducting YBa2Cu3O7-x. PMID- 9996334 TI - Experimental consequences of the uniform resonating-valence-bond state. PMID- 9996336 TI - Optical excitations in Bi2Sr2CuO6 and Bi2Sr2CaCu2O8: Evidence for localized (excitonic) and delocalized charge-transfer gaps. PMID- 9996337 TI - Asymmetrical effects of copper-site holes versus oxygen-site holes in La-Sr-Cu-O. PMID- 9996338 TI - Meissner effect and the plasmon spectrum in an interacting-anyon system. PMID- 9996339 TI - Entropy transport in high-Tc superconductors in the fluctuation regime. PMID- 9996340 TI - Magnons in random S=1 antiferromagnetic chains. PMID- 9996341 TI - Relation between the chiral-spin-liquid state and the chiral SU(2) Wess-Zumino Witten model. PMID- 9996342 TI - Structure of the low-temperature phase of molybdenum (001) investigated by helium atom scattering. PMID- 9996343 TI - Defect-concentration dependence of the spin-density-wave transport in the organic conductor (TMTSF)2PF6 (TMTSF=tetra- methyltetraselenafulvalene). PMID- 9996344 TI - Three-dimensional q-state Potts model: Monte Carlo study near q=3. PMID- 9996345 TI - Experimental verification of activated critical dynamics in the d=3 random-field Ising model. PMID- 9996346 TI - Strong dichroism in the Dy 3d-->4f x-ray absorption at Dy/Si(111) interfaces. PMID- 9996347 TI - Non-Rayleigh statistics of waves in random systems. PMID- 9996348 TI - Ground-state properties of two-dimensional antiferromagnetic quantum XXZ models. PMID- 9996349 TI - Coexistence of proton-glass and ferroelectric order in Rb1-x(NH4)xH2AsO4. PMID- 9996351 TI - Non-Ohmic conductivity in the fluctuation regime of charge- and spin-density-wave systems. PMID- 9996350 TI - Magnetic domain walls in thick iron films. PMID- 9996352 TI - Giant magnetoresistive in soft ferromagnetic multilayers. PMID- 9996353 TI - Energy-transfer processes in the 1T2g and 3T2g excited states of Ni2+:MgO. PMID- 9996354 TI - NaLa(MoO4)2 as a laser host material. PMID- 9996355 TI - ESR centers in reduced stabilized zirconia. PMID- 9996356 TI - Mossbauer line-shape parameters for 183W and 191Ir in metallic tungsten and iridium. PMID- 9996357 TI - Mossbauer line-shape parameters for 159Tb in TbAl2 and Tb4O7. PMID- 9996358 TI - Exact theory of long-wavelength one-phonon amplitudes in atom-surface scattering. PMID- 9996359 TI - Computer-simulation analysis of the ESR spectra of V-type centers in irradiated heavy-metal fluoride glasses. PMID- 9996360 TI - Surface analysis of cleaved single-crystalline CaSi2 by Auger electron spectroscopy. PMID- 9996361 TI - Tunneling and spin-lattice relaxation of hydrogen dissolved in scandium metal. PMID- 9996362 TI - One-phonon calculation of atom-surface inelastic scattering of the He-Cu(111) system. PMID- 9996363 TI - Second-harmonic generation and origin of polar configuration in KTaO3:Li. PMID- 9996364 TI - Uncommon nuclear-spin relaxation in fluorozirconate glasses at low temperatures. PMID- 9996365 TI - Theory of electron-stimulated desorption of physisorbed species through a strongly bonding excited state. PMID- 9996366 TI - Phenomenology of the plastic flow of amorphous solids induced by heavy-ion bombardment. PMID- 9996367 TI - Quadrupolar perturbed 14N NMR in the structurally commensurate and incommensurate phases of ammonium tetrachlorozincate. PMID- 9996368 TI - Determination of the shape and size of aggregated phases in NaCl:Mn2+ by small angle neutron scattering. PMID- 9996370 TI - Influence of exchange effects on the plasmon excitation spectrum of metals: Application in the case of beryllium. PMID- 9996369 TI - Symmetry properties of Raman heterodyne signals in Pr3+:LaF3. PMID- 9996371 TI - Elastic electron backscattering from gold. PMID- 9996373 TI - Ab initio Green's-function calculations on the Auger spectra of polyethylene. PMID- 9996372 TI - Infrared study of oxygen vacancies in KTaO3. PMID- 9996375 TI - Density-functional calculation of effective Coulomb interactions in metals. PMID- 9996374 TI - Nuclear-quadrupole-resonance study of pseudospin dynamics in a quasi-one dimensional XY system. PMID- 9996376 TI - Linear and nonlinear conductivity of a superconductor near Tc. PMID- 9996377 TI - Quantum fluctuations and charging effects in small tunnel junctions. PMID- 9996378 TI - Many-body theory of atomic deuterium. PMID- 9996380 TI - Reversible magnetization and torques in anisotropic high- kappa type-II superconductors. PMID- 9996379 TI - Self-consistent electronic structure of a vortex line in a type-II superconductor. PMID- 9996381 TI - Magnetic-flux quanta in superconducting thin films observed by electron holography and digital phase analysis. PMID- 9996382 TI - Ground state of the uniformly frustrated two-dimensional XY model near f=1/2. PMID- 9996383 TI - Surface-impedance measurements of superconducting NbN films. PMID- 9996384 TI - Possibility of the high-Tc oxide Y-Ba-Cu-O as a Bardeen-Cooper-Schrieffer superconductor. PMID- 9996385 TI - Thermal-expansion measurements for Lu5Ir4Si10, Lu5Rh4Si10, Sc5Ir4Si10, and Tm5Ir4Si10: Charge-density-wave effects. PMID- 9996386 TI - Phase transitions in the superconducting compound Lu5Rh4Si10 at ambient and high pressure. PMID- 9996388 TI - Low-temperature physical properties of R5Ir4Si10 (R=Dy, Ho, Er, Tm, and Yb) compounds. PMID- 9996387 TI - Competition between superconductivity and charge-density waves in the pseudoternary system (Lu1-xScx)5Ir4Si10. PMID- 9996389 TI - Effects of charging-energy fluctuations on an anomalous behavior of mesoscopic Josephson junctions. PMID- 9996390 TI - Singularity and nonlinearity in the Kapitza resistance between gold and superfluid 4He near T lambda. PMID- 9996391 TI - Phase boundary of a cubic superconducting circuit in a magnetic field of arbitrary magnitude and direction. PMID- 9996392 TI - Solitons in hydrogen-bonded chains: A microscopic model. PMID- 9996393 TI - Unified symmetry-breaking theory of Bose-Einstein condensation in superfluids. PMID- 9996394 TI - Superconductivity in ion-beam-mixed layered Au-Si thin films. PMID- 9996395 TI - Dispersion relations and density of states of the collective oscillations of the electronic dipoles in high-Tc superconductors. PMID- 9996396 TI - dc properties of series-parallel arrays of Josephson junctions in an external magnetic field. PMID- 9996398 TI - Electromagnetic response of a thin type-II superconducting cylindrical shell. PMID- 9996397 TI - Acoustic-phonon emission by two-dimensional plasmons. PMID- 9996399 TI - Doped antiferromagnet: The instability of homogeneous magnetic phases. PMID- 9996400 TI - Positron annihilation on single crystals of YBa2Cu3O7-x. PMID- 9996401 TI - Vortex pinning by twin boundaries in copper oxide superconductors. PMID- 9996402 TI - Orientational and positional order in flux lattices of type-II superconductors. PMID- 9996403 TI - Two-dimensional vortices in a stack of thin superconducting films: A model for high-temperature superconducting multilayers. PMID- 9996404 TI - Infrared properties of T'-phase R2CuO4 insulating compounds. PMID- 9996405 TI - Structural and transport measurements in La1.8Sr0.2NiO4+ delta. PMID- 9996406 TI - Directional vortex-flux bifurcation in polycrystalline YBa2Cu3O7 rotated in a magnetic field. PMID- 9996407 TI - Synthesis and characterization of the superconducting cuprates (Pb,Cu)Sr2(Y,Ca)Cu2Oz. PMID- 9996408 TI - Electron-spin resonance and ferromagnetism in a copper oxide: La4Ba2Cu2O10. PMID- 9996410 TI - Superconducting La2CuO4+x prepared by oxygenation at high pressure: A Raman scattering study. PMID- 9996409 TI - Transport and magnetic properties of Tl2Ba2CuO6+ delta showing a delta -dependent gradual transition from an 85-K superconductor to a nonsuperconducting metal. PMID- 9996411 TI - Spin dynamics in a frustrated magnet with short-range order. PMID- 9996413 TI - Scanning tunneling microscopy and spectroscopy of Bi-Sr-Ca-Cu-O 2:2:1:2 high temperature superconductors. PMID- 9996412 TI - Cluster study of the t-J model: Chiral fluctuations. PMID- 9996414 TI - Crystal-field splittings and magnetic properties of Pr3+ and Nd3+ in RBa2Cu3O7. PMID- 9996415 TI - Superconductivity at 67 K in (Pb,Cu)Sr2(Ca,Y)Cu2O7 by precise adjustment of oxygen. PMID- 9996416 TI - Optical spectra of La2-xSrxCuO4: Effect of carrier doping on the electronic structure of the CuO2 plane. PMID- 9996417 TI - Thermoelectric power of Ba1-xKxBiO3. PMID- 9996418 TI - Spin-fluctuation effects on superconductivity. PMID- 9996419 TI - Measurement of the Ginzburg-Landau parameter kappa 2(T) for polycrystalline YBa2Cu3O7- delta. PMID- 9996420 TI - Flux pinning at grain boundaries in Bi-(Pb)-Sr-Ca-Cu-O ceramic superconductors. PMID- 9996422 TI - Transport anomalies in the high-temperature hopping conductivity and thermopower of Sr-doped La(Cr,Mn)O3. PMID- 9996421 TI - Cluster-assembled overlayers and high-temperature superconductors. PMID- 9996423 TI - Mean-field phase diagram of a two-band t-J model for CuO2 layers. PMID- 9996424 TI - One-hole spectral densities in the polarized t-J model. PMID- 9996425 TI - Flux-line entanglement in high-Tc superconductors. PMID- 9996426 TI - Pinning in layered inhomogeneous superconductors. PMID- 9996427 TI - Electron-energy-loss studies of core edges in (Tl0.5Pb0.5)(Ca1-xYx)Sr2Cu2O7- delta. PMID- 9996429 TI - Conserving approximations for strongly fluctuating electron systems. II. Numerical results and parquet extension. PMID- 9996428 TI - Vertex operators and spinon edge excitations in the spin-singlet quantum Hall effect. PMID- 9996430 TI - Interaction between spin-density waves in magnetic alloys. PMID- 9996431 TI - Search for a correlation length in a simulation of the glass transition. PMID- 9996432 TI - Langevin molecular dynamics of interfaces: Nucleation versus spiral growth. PMID- 9996434 TI - Demagnetization energy and magnetic permeability tensor of spheroidal magnetic particles dispersed in cubic lattices. PMID- 9996433 TI - Reentrant magnetic behavior in fcc Co-Cu alloys. PMID- 9996435 TI - Thermal expansion associated with the charge-density wave in K0.3MoO3. PMID- 9996436 TI - Shapes of wetted solids and sinters. PMID- 9996437 TI - Nonequilibrium statistical mechanics of the spin-1/2 van der Waals model. I. Time evolution of a single spin. PMID- 9996438 TI - Nonequilibrium statistical mechanics of the spin-1/2 van der Waals model. II. Autocorrelation function of a single spin and long-time tails. PMID- 9996439 TI - Spin glass on the finite-connectivity lattice: The replica solution without replicas. PMID- 9996440 TI - Distribution of terrace widths on a vicinal surface within the one-dimensional free-fermion model. PMID- 9996442 TI - Magnetism in small vanadium clusters. PMID- 9996441 TI - Generalized description of thermally stimulated processes without the quasiequilibrium approximation. PMID- 9996443 TI - Theory and numerical simulation of optical properties of fractal clusters. PMID- 9996444 TI - Spin equilibrium of Co3+ complexes influenced by a magnetic field. PMID- 9996445 TI - Static scaling in a short-range Ising spin glass. PMID- 9996447 TI - Correlations in the two-dimensional Hubbard model. PMID- 9996446 TI - Universal features in growth kinetics: Some experimental tests. PMID- 9996448 TI - Thermal Bethe-ansatz study of the correlation length of the one-dimensional S=1/2 Heisenberg antiferromagnet. PMID- 9996450 TI - Nonuniversality in two-dimensional percolating systems with a broad distribution of bond conductances. PMID- 9996449 TI - Anomalous dielectric response in tetrathiafulvalene-p-chloranil as observed in temperature- and pressure-induced neutral-to-ionic phase transition. PMID- 9996451 TI - CeCo0.89Ge2: A heavy-fermion system. PMID- 9996453 TI - Molecular-dynamics study of the effects of strain on interstitial diffusion in a hard-sphere model of a binary crystalline solid. PMID- 9996452 TI - Observability of a quasilinear temperature dependence of the magnetization in a semi-infinite ferromagnet. PMID- 9996454 TI - Thermodynamic and transport properties of (CexGd1-x)Cu6 for 0 <= x <= 1. PMID- 9996456 TI - Magnetic-susceptibility and magnetization measurements of polyacenic semiconductive materials. PMID- 9996455 TI - Transient currents in nematic liquid crystals. PMID- 9996458 TI - Elasticity and the Landau-Peierls instability in the smectic twist-grain-boundary phase. PMID- 9996457 TI - Diffraction from random alloys. PMID- 9996459 TI - Dielectric nonlinearity and spontaneous polarization of KTa1-xNbxO3 in the diffuse transition range. PMID- 9996460 TI - Exact analytic dispersion relations for dipolar magnetostatic and magnetoretarded modes in finite magnetic superlattices. PMID- 9996461 TI - Dipolar-glass model for lead magnesium niobate. PMID- 9996462 TI - Square-lattice Heisenberg antiferromagnet at T=0. PMID- 9996463 TI - Kosterlitz-Thouless transition with symmetry-breaking fields and quenched random interactions. PMID- 9996464 TI - Structure of the microscopic theory of the hierarchical fractional quantum Hall effect. PMID- 9996466 TI - Detection of second-order quadrupolar spin-lattice coupling mechanisms in metallic antimony using multifrequency pulsed nuclear quadrupole resonance. PMID- 9996465 TI - Residual properties of a two-level system. PMID- 9996467 TI - Theoretical study of the onset of magnetism in (Fe)x/(Ru)x superlattices. PMID- 9996468 TI - Spin glass with two replicas on a Bethe lattice. PMID- 9996469 TI - Conduction delays in switching NbSe3: Sensitive dependence on the initial configuration. PMID- 9996470 TI - Optical absorption, magnetic circular dichroism, and reduction factors in the Jahn-Teller system E PMID- 9996471 TI - Magnetic-field effects on the correlation functions in the one-dimensional strongly correlated Hubbard model. PMID- 9996472 TI - Molecular-dynamics study of incommensurate phases in a three-dimensional crystal. PMID- 9996473 TI - Neutron-scattering investigations of the Kohn anomaly and of the phase and amplitude charge-density-wave excitations of the blue bronze K0.3MoO3. PMID- 9996474 TI - Dynamic structure factor of a one-dimensional Peierls system. PMID- 9996476 TI - Relaxation processes due to collisions involving conduction electrons and magnon solitons in magnetic semiconductors. PMID- 9996475 TI - Neutron-depolarization theory in particulate media. PMID- 9996477 TI - Heat capacity and entropy of nonstoichiometric magnetite Fe3(1- delta )O4: The thermodynamic nature of the Verwey transition. PMID- 9996478 TI - Non-Gaussian approach to critical fluctuations in the Landau-Ginzburg model and finite-size scaling. PMID- 9996479 TI - XY model on a Sierpinski gasket. PMID- 9996480 TI - Asymmetric phases in the mean-field theory of the axial next-nearest-neighbor Ising model. PMID- 9996481 TI - Discreteness effects on a sine-Gordon breather. PMID- 9996482 TI - Quantum effects in Heisenberg antiferromagnetic thin films. PMID- 9996483 TI - Non-Markovian theory of tunneling in dissipative media. PMID- 9996484 TI - Thermal expansion and magnetostriction of CeAl2. PMID- 9996486 TI - Linked-cluster expansion around the atomic limit of the Hubbard model. PMID- 9996485 TI - General cluster Monte Carlo dynamics. PMID- 9996487 TI - Some magnetic properties of the S=1/2 Ising system with the random exchange integral: The Gaussian approximation. PMID- 9996488 TI - Fracton dimensionalities for field-biased diffusion-limited aggregation clusters. PMID- 9996490 TI - Envelope-kink excitations in a quantum anisotropic antiferromagnetic Heisenberg chain. PMID- 9996489 TI - Diamond-type hierarchical lattices for the Potts antiferromagnet. PMID- 9996491 TI - Critical and scaling properties of the Soukoulis-Economou model in one dimensional incommensurate systems. PMID- 9996492 TI - Magnetic properties of R ions in RCo5 compounds (R=Pr, Nd, Sm, Gd, Tb, Dy, Ho, and Er). PMID- 9996493 TI - Magnetic-field dependence of photon-echo decays in ruby. PMID- 9996494 TI - Near-edge study of molecular oxygen and nitrogen clusters on a krypton surface. PMID- 9996495 TI - Infrared observation of two-fluid superconductivity in YBa2Cu3O7-x. PMID- 9996496 TI - Additional short-wavelength vibratory modes from a large (bi)polaron. PMID- 9996497 TI - Phase diagram of superconducting-normal-metal superlattices. PMID- 9996499 TI - Anisotropic thermoelectric power in YBa2Cu3O7-x single crystals under pressures up to 8 GPa. PMID- 9996498 TI - Thermally activated infrared-active vibrational mode in BaBiO3. PMID- 9996500 TI - Onset of high-temperature superconductivity in the two-dimensional limit. PMID- 9996501 TI - Response of YBa2Cu3O7- delta grain-boundary junctions to short light pulses. PMID- 9996502 TI - Microwave absorption by vortex cores in the high-temperature superconductor YBa2Cu3O7-x. PMID- 9996504 TI - Sensitivity of the multiple-scattering speckle pattern to the motion of a single scatterer. PMID- 9996503 TI - In situ growth and flux pinning in Ag-doped YBa2Cu3O7-y thin films. PMID- 9996505 TI - Random matrices, fractional statistics, and the quantum Hall effect. PMID- 9996506 TI - Linked-tetrahedra spin chain: Exact ground state and excitations. PMID- 9996507 TI - Polaronic conduction in n-type BaTiO3 doped with La2O3 or Gd2O3. PMID- 9996509 TI - Incompletely ordered phase in the three-dimensional six-state clock model: Evidence for an absence of ordered phases of XY character. PMID- 9996508 TI - Hubbard U= PMID- 9996510 TI - Orientational-ordering transition fcc-Pa3 of Ar1-x(N2)x. PMID- 9996511 TI - Spin-dependent covalence in La2CuO4- delta from neutron diffraction. PMID- 9996512 TI - Reentrant transition in the Ising spin system with an infinite-range coupling and a Gaussian random field. PMID- 9996513 TI - Comment on "Exact lower bounds to the ground-state energy of spin systems: The two-dimensional S=1/2 antiferromagnetic Heisenberg model" PMID- 9996514 TI - Comment on "Morphology of micromagnetics" PMID- 9996515 TI - Reply to "Comment on 'Morphology of micromagnetics' " PMID- 9996516 TI - Erratum: Structure of noise generated on diffusion fronts PMID- 9996517 TI - Monte Carlo simulation study of domain growth in an Ising spin glass. PMID- 9996519 TI - Metal-semiconductor transition in partially compensated Ge:Sb. PMID- 9996518 TI - Crossover in the critical field of Pb/Ge multilayers: From single-film to coupled behavior. PMID- 9996520 TI - Frequency dependence of Shapiro steps in Josephson-junction arrays. PMID- 9996521 TI - Modulation-free bismuth-lead cuprate superconductors: BiPbSr1+xL1-xCuO6 and BiPbSr2Y1-xCaxCu2O8. PMID- 9996522 TI - Spectral shift of the magnetic cross section in superconducting YBa2Cu3O6+x. PMID- 9996524 TI - Supersymmetric t-J model: An exact result for two dimensions. PMID- 9996523 TI - Magnetic critical fields of Y-Ba-Cu-O superconductors in the Lawrence-Doniach model with inequivalent layers. PMID- 9996525 TI - Dynamic properties of a high-Tc superconductor: Direct evidence for non-BCS behavior. PMID- 9996526 TI - Constructing quasiparticle operators in strongly correlated systems. PMID- 9996527 TI - Low-temperature magnetic relaxation in YBa2Cu3O7- delta : Evidence for quantum tunneling of vortices. PMID- 9996528 TI - Photoelectron microscopy and spectroscopy of Bi2Sr2-x- Ca1+xCu2O8+y(100). PMID- 9996529 TI - Voltage quantization by ballistic vortices in two-dimensional superconductors. PMID- 9996530 TI - Effect of magnetic field on thermal conductivity of YBa2Cu3O7- delta single crystals. PMID- 9996531 TI - Critical sheet resistance observed in high-Tc oxide-superconductor Nd2-xCexCuO4 thin films. PMID- 9996532 TI - Electronic and structural effects of oxygen doping in Bi2Sr2CaCu2Ox superconductors characterized by tunneling microscopy. PMID- 9996533 TI - Hole dynamics and effective hole-hole interaction in a quantum antiferromagnet. PMID- 9996535 TI - Vapor-pressure study of the melting of two-dimensional argon adsorbed on BN. PMID- 9996534 TI - Superconductivity and magnetic order in the Cu(2) planes in Fe-doped YBa2Cu4O8. PMID- 9996536 TI - Effects of translational symmetry breaking induced by the boundaries in a driven diffusive system. PMID- 9996537 TI - Electronic properties of icosahedral, approximant, and amorphous phases of an Al Cu-Fe alloy. PMID- 9996538 TI - Field-induced Kosterlitz-Thouless transition in the zero-temperature triangular Ising antiferromagnet. PMID- 9996539 TI - Dynamics of longitudinal and transverse fluctuations above Tc in EuS. PMID- 9996540 TI - Exact solution of an anisotropic centered honeycomb Ising lattice: Reentrance and partial disorder. PMID- 9996541 TI - Inelastic-neutron-scattering measurements of phonons in icosahedral Al-Li-Cu. PMID- 9996542 TI - Optical absorption measurements of hydrogen at megabar pressures. PMID- 9996543 TI - Ground state of ferromagnetic nickel and magnetic circular dichroism in Ni 2p core x-ray-absorption spectroscopy. PMID- 9996544 TI - Spiral states in the square-lattice Hubbard model. PMID- 9996545 TI - Bounds on ferromagnetism at T>0 in the hard-core electron lattice gas. PMID- 9996546 TI - Chemically driven phason disorder in icosahedral Al-Pd-Mn alloys. PMID- 9996547 TI - Incommensurate charge-density-wave state in alpha -uranium: A high-resolution x ray and neutron-scattering study. PMID- 9996549 TI - Theoretical atomic-force-microscopy study of a stepped surface: Nonlocal effects in the probe. PMID- 9996548 TI - Noncubic symmetry in garnet structures studied using extended x-ray-absorption fine-structure spectra. PMID- 9996550 TI - Surface energy and stress of lead (111) and (110) surfaces. PMID- 9996551 TI - Reconstructions of Au films on Pd(110). PMID- 9996552 TI - Influence of the anisotropy of the positron wave function on the calculation of the momentum density of positron annihilation pairs. PMID- 9996553 TI - Thermal vibration and melting from a local perspective. PMID- 9996554 TI - Efficient pseudopotentials for plane-wave calculations. II. Operators for fast iterative diagonalization. PMID- 9996555 TI - Surface-plasmon field-enhanced multiphoton photoelectric emission from metal films. PMID- 9996556 TI - Electronic properties of the Penrose lattice. I. Energy spectrum and wave functions. PMID- 9996557 TI - Electronic properties of the Penrose lattice. II. Conductance at zero temperature. PMID- 9996559 TI - Spin scaling of the electron-gas correlation energy in the high-density limit. PMID- 9996558 TI - Photoemission investigation of the electronic structure of Fe-Pd and Fe-Pt alloys. PMID- 9996560 TI - Periodic charge-density modulations on graphite near platinum particles. PMID- 9996562 TI - Surface phonons and dipole activity of Si(111)2 x 1 from ab initio calculations. PMID- 9996561 TI - Variational thermodynamic calculations for liquid transition metals. PMID- 9996563 TI - Influence of Coulomb interaction on the photon echo in disordered semiconductors. PMID- 9996565 TI - Structural and electronic properties of alpha -Sn, CdTe, and their PMID- 9996564 TI - Electrical conductivity of amorphous silicon doped with rare-earth elements. PMID- 9996566 TI - First-principles study of intervalley mixing: Ultrathin GaAs/GaP superlattices. PMID- 9996567 TI - Full-band-structure calculation of second-harmonic generation in odd-period strained (Si)n/(Ge)n superlattices. PMID- 9996568 TI - Free-ion yields for several silicon-, germanium-, and tin-containing liquids and their mixtures. PMID- 9996569 TI - Resonant tunneling in a quasi-one-dimensional wire: Influence of evanescent modes. PMID- 9996570 TI - Theory of magnetoplasmons in semiconductor superlattices in the Voigt geometry: A Green-function approach. PMID- 9996571 TI - Energy-loss rates of two-dimensional electrons at a GaAs/AlxGa1-xAs interface. PMID- 9996572 TI - Intervalley scattering in the two-dimensional electron gas near an AlxGa1 xAs/GaAs heterojunction. PMID- 9996573 TI - Tight-binding theory of interchain coupling in doped polyacetylene. PMID- 9996574 TI - Simulation of many-electron correlations in a resonant-tunneling diode. PMID- 9996576 TI - Tunneling and hopping conduction in Langmuir-Blodgett thin films of poly(3 hexylthiophene). PMID- 9996575 TI - Cation surface excitons in Sb/III-V interfaces. PMID- 9996577 TI - Photoluminescence due to a bound-to-bound transition in a GaAs-Al0.3Ga0.7As quantum-well structure. PMID- 9996578 TI - Continuum theories of optical phonons and polaritons in superlattices: A brief critique. PMID- 9996579 TI - Inverse correlation between the intensity of luminescence excited by electrons and by visible light in chemical-vapor-deposited diamond films. PMID- 9996580 TI - Optically detected electron-nuclear double resonance of S=1 states of defects in semiconductors: PGa-YP in GaP. PMID- 9996581 TI - Line-shape model for the modulated reflectance of multiple quantum wells. PMID- 9996582 TI - Quasiparticle energies for cubic BN, BP, and BAs. PMID- 9996584 TI - Formation energies, bond lengths, and bulk moduli of ordered semiconductor alloys from tight-binding calculations. PMID- 9996583 TI - Dielectric properties of single-crystal TiSi2 from 0.6 to 20 eV. PMID- 9996585 TI - Resonant Raman scattering in PMID- 9996586 TI - Soliton lattice in highly doped trans-polyacetylene. PMID- 9996587 TI - Electrical and optical properties of titanium-related centers in silicon. PMID- 9996588 TI - Electronic structure of polypyrrole films. PMID- 9996589 TI - Cyclotron resonance of a magnetopolaron in a quasi-two-dimensional system at finite temperatures. PMID- 9996590 TI - E' centers in tridymite silicon dioxide: A theoretical study. PMID- 9996591 TI - Low-temperature properties of a dipolar glass: A study of KBr1-x(CN)x using dielectric echoes. PMID- 9996592 TI - Dielectric long-time relaxation of amorphous materials at low temperatures. PMID- 9996594 TI - Solving the phonon Boltzmann equation with the variational method. PMID- 9996593 TI - Ab initio band-structure calculations for alkaline-earth oxides and sulfides. PMID- 9996595 TI - Exchange electron-hole interaction at the isoelectronic oxygen trap in zinc selenide. PMID- 9996596 TI - Theoretical study of high-pressure phases of tin. PMID- 9996597 TI - Electronic structure of small clusters of Li and a Li-Mg compound. PMID- 9996598 TI - Semiempirical model of isotopic shifts of the band gap. PMID- 9996599 TI - Binding energy of on-axis hydrogenic and nonhydrogenic donors in a GaAs/Ga1 xAlxAs quantum-well wire of circular cross section. PMID- 9996600 TI - Infrared-absorption coefficient for shallow donors in a quantum well. PMID- 9996602 TI - Spontaneous generation of plasmons by ballistic electrons. PMID- 9996601 TI - Linear and nonlinear optical properties of (GaAs)m/(AlAs)n superlattices. PMID- 9996603 TI - Additional intersubband plasmons in quasi-one-dimensional systems. PMID- 9996604 TI - Effect of dielectric screening on the donor binding energy in silicon and germanium. PMID- 9996605 TI - H2O adsorption on Ge(100): An angle-resolved photoelectron spectroscopy study. PMID- 9996606 TI - Criterion for DNA melting in the mean-field modified self-consistent phonon theory. PMID- 9996607 TI - Energetics in the initial stage of oxidation of silicon. PMID- 9996609 TI - Optical spectroscopy of Eu2+ ions coupled to CN- and OCN- molecular ions in KCl. PMID- 9996610 TI - Erratum: Electron-LO-phonon scattering rates in semiconductor quantum wells PMID- 9996608 TI - Occurrence of solid noble-gas inclusions in ion-beam-implanted magnesium oxide. PMID- 9996612 TI - Direct observation of anelastic bond-orientational anisotropy in amorphous Tb26Fe62Co12 thin films by x-ray diffraction. PMID- 9996611 TI - Erratum: Variational quantum Monte Carlo nonlocal pseudopotential approach to solids: Formulation and application to diamond, graphite, and silicon PMID- 9996613 TI - "Supermodulus effect" in Cu/Pd and Cu/Ni superlattices. PMID- 9996614 TI - Role of elastic scattering in ballistic-electron-emission microscopy of Au/Si(001) and Au/Si(111) interfaces. PMID- 9996615 TI - Influence of barrier height on carrier dynamics in strained InxGa1-xAs/GaAs quantum wells. PMID- 9996616 TI - Indium-induced reconstructions of the Si(100) surface. PMID- 9996617 TI - Long-wavelength infrared spectroscopy of an asymmetrically structured Ga0.6Al0.4As/GaAs superlattice. PMID- 9996619 TI - Interface-phonon-mediated magnetopolaronic effect on impurity transition energies in quantum wells. PMID- 9996618 TI - Two-level and three-level resonant measurements of impurity-bound magnetopolarons in multiple-quantum-well structures. PMID- 9996621 TI - Resonances in the hopping probability between flexible quantum dots: The case of superlattices under parallel electric and magnetic fields. PMID- 9996620 TI - Interior contacts for probing the equilibrium between magnetic edge channels in the quantum Hall effect. PMID- 9996622 TI - Quantum Hall effect in double-quantum-well systems. PMID- 9996624 TI - Fabry-Perot transmission resonances in tunneling microscopy. PMID- 9996623 TI - Spontaneous polarization in quantum-dot systems. PMID- 9996625 TI - Determination of the extension of the heavy-hole wave function in GaAs by photomodulation spectroscopy. PMID- 9996627 TI - Tunneling in a self-consistent dynamic image potential. PMID- 9996626 TI - Hot-exciton luminescence in ZnTe/MnTe quantum wells. PMID- 9996629 TI - Elastic scattering of low-energy electrons from oxygen-covered Si surfaces. PMID- 9996628 TI - Li impurity in ZnSe: Electronic structure and the stability of the acceptor. PMID- 9996630 TI - Quantum oscillation of transverse resistance and resistance reciprocity as a point-contact boundary problem. PMID- 9996631 TI - Magnetotunneling in a coupled two-dimensional-one-dimensional electron system. PMID- 9996632 TI - Stress-induced layer-by-layer growth of Ge on Si(100). PMID- 9996634 TI - Local adsorbate-induced effects on dynamical charge transfer in ion-surface interactions. PMID- 9996633 TI - Two-state approximation in the Coulomb-blockade theory: Simple analytical results for a double-tunnel junction. PMID- 9996635 TI - Order-disorder transition in silver-intercalated niobium disulfide compounds. I. Structural determination of Ag0.6NbS2. PMID- 9996637 TI - Simple numerical approach for determining the optical response of a nonlinear dielectric film for both TE and TM waves. PMID- 9996636 TI - Order-disorder transition in silver-intercalated niobium disulfide compounds. II. Magnetic and electrical properties. PMID- 9996638 TI - Electronic and magnetic structure of {111} stacking faults in nickel. PMID- 9996639 TI - First-principles calculations of adatom binding and interaction on Rh(001). PMID- 9996640 TI - Coulomb barriers in the dissociation of doubly charged clusters. PMID- 9996641 TI - Electronic structure of the (111) and (100) surfaces of delta -Pu. PMID- 9996642 TI - Mesoscopic fluctuations of the ultrasound attenuation. PMID- 9996643 TI - Positron-annihilation and time-differential perturbed-angular-correlation studies of the amorphous Al-Mn-Si alloy. PMID- 9996645 TI - Calculation of energy barriers for physically allowed lattice-invariant strains in aluminum and iridium. PMID- 9996644 TI - Vacancy-solute interactions in Cu, Ni, Ag, and Pd. PMID- 9996646 TI - Superstoichiometry, accelerated diffusion, and nuclear reactions in deuterium implanted palladium. PMID- 9996647 TI - Temporal evolution of the longitudinal- and transverse-phonon distributions in nonequilibrium metal films. PMID- 9996648 TI - Probing the f electrons in URu2Si2 with positrons: A theoretical investigation. PMID- 9996649 TI - Positron-annihilation study of the electronic structure of URu2Si2. PMID- 9996650 TI - Ab initio band-structure studies of beryllium and beryllium-hydrogen ultrathin films. PMID- 9996651 TI - Self-consistent Green's-function technique for surfaces and interfaces. PMID- 9996652 TI - N6,7O4,5O4,5 Auger spectrum of metallic Au. PMID- 9996654 TI - Optical properties of ZnSe. PMID- 9996653 TI - Local perturbation and induced magnetization originating from 3d impurities in Pd. PMID- 9996656 TI - Surface core-level shifts and relaxation of group-IVA-element chalcogenide semiconductors. PMID- 9996655 TI - Characterization of Cd1-yZnyTe(111) and Hg1-xCdxTe(111) real surfaces by x-ray photoelectron diffraction. PMID- 9996657 TI - Band structure, quantum confinement, and exchange splitting in Sc1-xErxAs epitaxial layers buried in GaAs. PMID- 9996658 TI - Raman and reflectivity spectra of cubic Cd1-xMnxSe epilayers grown by molecular beam epitaxy. PMID- 9996659 TI - InP(110) oxidation with O2, NO, and N2O at 20 K: Temperature and photon-energy dependencies. PMID- 9996660 TI - Electronic structure of strained GaAs/GaP (001) superlattices. PMID- 9996661 TI - Structural phase transitions and optical absorption of LiInSe2 under pressure. PMID- 9996662 TI - Acceptor excitation spectra in germanium in a uniform magnetic field. PMID- 9996663 TI - Efficient band-structure calculations of strained quantum wells. PMID- 9996664 TI - Magnetoluminescence of the two-dimensional electron-hole fluid. PMID- 9996665 TI - Photoemission study of the formation of the CaF2/GaAs(100) interface. PMID- 9996666 TI - Raman-scattering and optical studies of argon-etched GaAs surfaces. PMID- 9996667 TI - "Spin"-flip scattering of holes in semiconductor quantum wells. PMID- 9996668 TI - Incident-beam effects in electron-stimulated Auger-electron diffraction. PMID- 9996670 TI - Jahn-Teller effect in the 4T1 state of Mn2+ in GaP. PMID- 9996669 TI - Full-band-structure calculation of first-, second-, and third-harmonic optical response coefficients of ZnSe, ZnTe, and CdTe. PMID- 9996671 TI - Empty electronic states at rare-earth-metal-silicon interfaces: Inverse photoemission of Gd and Eu on Si(111)7 x 7. PMID- 9996672 TI - Ultrasonic relaxation of interstitial aluminum in irradiated silicon. PMID- 9996673 TI - Effect of multi-ion screening on the electronic transport in doped semiconductors: A molecular-dynamics analysis. PMID- 9996674 TI - Spatial measurements of moving space-charge domains in p-type ultrapure germanium. PMID- 9996675 TI - Path-integral treatment of the large-bipolaron problem. PMID- 9996677 TI - Disorder-assisted tunneling through a double-barrier resonant-tunneling structure. PMID- 9996676 TI - Electronic states in mixed pseudobinary (Pb,Sr)S crystals. PMID- 9996678 TI - Anomalous behavior of cyclotron resonance in GaAs/Al0.28Ga0.72As high-electron mobility transistor structures. PMID- 9996679 TI - Theory of even-parity states and two-photon spectra of conjugated polymers. PMID- 9996680 TI - Temperature dependence of the dc conductivity of undoped a-Si1-xGex:H alloys: Influence of metastability. PMID- 9996681 TI - Planar force-constant models and internal strain parameter of Ge and Si. PMID- 9996682 TI - Dynamical models of hydrogenated amorphous silicon. PMID- 9996683 TI - Inelastic-electron-scattering investigation of clean and hydrogen-exposed InP(110) surfaces. PMID- 9996685 TI - Alternating anion-cation bond strengths in CdGeAs2: Application to the family of ternary pnictides. PMID- 9996684 TI - Chemical bond and electronic states at the CaF2-Si(111) and Ca-Si(111) interfaces. PMID- 9996686 TI - Angle-resolved photoelectron spectroscopy study of the surface electronic structure of ZnTe(110). PMID- 9996688 TI - Effective-mass theory for superlattices grown on (11N)-oriented substrates. PMID- 9996687 TI - Transient nucleation following pulsed-laser melting of thin silicon films. PMID- 9996689 TI - Infrared-active excitations in tunneling superlattices and d-parameter theory. PMID- 9996690 TI - Spin-orbit structure of F centers and F -center-OH- pairs in cesium halides. PMID- 9996691 TI - F center associated with a pair of OH- defects in cesium halides. PMID- 9996693 TI - Relaxation mechanisms in a benzyl chloride-toluene glass. PMID- 9996692 TI - Extended x-ray-absorption fine-structure study of alkali-metal halides under high pressure. PMID- 9996694 TI - Elasto-optical response of diamond at variable temperatures. PMID- 9996695 TI - Hellmann potential extended to next-nearest neighbors for alkali halide crystals. PMID- 9996696 TI - Electronic structure of S and Sn impurities in InP. PMID- 9996697 TI - Simulation study of transient behavior of photoconductivity. PMID- 9996698 TI - Infrared luminescence of ZnO:Cu2+(d9). PMID- 9996699 TI - Indirect interaction between localized impurities in polar semiconductors. PMID- 9996700 TI - Resonant tunneling through a symmetric triple-barrier structure. PMID- 9996702 TI - Chemical shift and zone-folding effects on the energy gaps of GaAs-AlAs (001) superlattices. PMID- 9996701 TI - Molecular-dynamics approach to lattice-relaxation effects on deep levels in semiconductors. PMID- 9996703 TI - Recombination processes in ZnS:Sm. PMID- 9996704 TI - Comment on "Microscopic theory of optic-phonon Raman scattering in quantum-well systems" PMID- 9996705 TI - Evidence for crystalline overpressurized Ar clusters in Al and Si. PMID- 9996706 TI - Far-infrared absorption by fractal metal clusters. PMID- 9996707 TI - Size effects, phase slip, and the origin of f- alpha noise in NbSe3. PMID- 9996708 TI - Change in Young's modulus at low frequency upon charge-density-wave depinning in TaS3. PMID- 9996709 TI - Phonon confinement in InAs/GaSb superlattices. PMID- 9996710 TI - Magnetic breakdown of a two-dimensional electron gas in a periodic potential. PMID- 9996711 TI - Transport through one-dimensional channels. PMID- 9996713 TI - Orientation dependence of growth quality in strained-layer superlattices: A model potential study of the Si-Ge system. PMID- 9996712 TI - Suppression and recovery of quantum Hall plateaus in a parabolic quantum well. PMID- 9996714 TI - Origin of the blueshift in the intersubband infrared absorption in GaAs/Al0.3Ga0.7As multiple quantum wells. PMID- 9996716 TI - Excitonic fine structure in the charge-transfer spectra of GaP:Fe. PMID- 9996715 TI - Dimensional resonances in wide parabolic quantum wells. PMID- 9996717 TI - Vacuum-ultraviolet spectroscopy of dialkyl polysilanes. PMID- 9996718 TI - Nucleation kinetic studies of a europium-doped aluminosilicate glass: Low frequency inelastic scattering and fluorescence line narrowing. PMID- 9996719 TI - Formal calculation of the pick-off annihilation rate for ortho- and parapositronium. PMID- 9996720 TI - Dynamics and kinetics of monolayer CH4 on MgO(001) studied by helium-atom scattering. PMID- 9996721 TI - Positron-induced Auger-electron study of the Ge(100) surface: Positron thermal desorption and surface condition. PMID- 9996722 TI - Band effects on neutralization of low-energy D+ scattering from ionic crystals. PMID- 9996724 TI - Crystallization study and hyperfine characterization of a Sn-O thin film with 181Ta. PMID- 9996723 TI - Perturbation expansions of the response function and the asymptotic regime. PMID- 9996725 TI - Trapping of point-contact-generated 29-cm-1 phonons in ruby. PMID- 9996727 TI - Surface-barrier reflection of diffusing positrons. PMID- 9996726 TI - Positron-reemission-microscope study of positron implantation and diffusion. PMID- 9996729 TI - pi phase in magnetic-layered superconductors. PMID- 9996728 TI - Penetration of an electron beam in a thin solid film: The influence of backscattering from the substrate. PMID- 9996730 TI - Direct calculation of conductance and conductance fluctuations in a disordered Fermi liquid. PMID- 9996732 TI - Superconducting micronets: A state-variable approach. PMID- 9996731 TI - Temperature dependence of the critical current of the superconducting microladder in zero magnetic field: Theory and experiment. PMID- 9996733 TI - Current-carrying states in Josephson junctions. PMID- 9996734 TI - Lattice instabilities near the critical V-V separation for localized versus itinerant electrons in LiV1-yMyO2 (M=Cr or Ti) Li1-xVO2. PMID- 9996735 TI - Self-induced steps in a small Josephson junction strongly coupled to a multimode resonator. PMID- 9996736 TI - Density dependence of the intramolecular distance in solid H2: A. Spectroscopic determination. PMID- 9996737 TI - Nonlinear analysis of the modulational instability of a tachyonic wave train in the damped dc-driven sine-Gordon model. PMID- 9996738 TI - Local structure of supercurrent flow past an impurity. PMID- 9996739 TI - Ginsburg-Landau equation around the superconductor-insulator transition. PMID- 9996740 TI - Temperature dependence of the critical pair-breaking current in thin-film, strong coupling superconductors. PMID- 9996741 TI - Phenomenological model of vortex dynamics in arrays of Josephson junctions. PMID- 9996742 TI - Pairing in two dimensions: A systematic approach. PMID- 9996744 TI - PIMC simulations of solid parahydrogen. PMID- 9996743 TI - Electromagnetic penetration depth and frequency-dependent optical conductivity for a proximity junction. PMID- 9996746 TI - Electronic states in oxide superconductors. PMID- 9996745 TI - Formulation of a self-consistent diagram method in the p-d mixing model. PMID- 9996747 TI - Quantitative description of hysteresis loops induced by rf radiation in long Josephson junctions. PMID- 9996748 TI - Thermodynamics for retarded d-wave interactions and arbitrary impurity concentrations. PMID- 9996749 TI - Anyons in spin liquids. PMID- 9996751 TI - Quasiparticle theory of the electron gas: A direct-interaction approach. PMID- 9996750 TI - Nonlinear electromagnetic rectification of BCS-paired electrons at a superconductor surface. PMID- 9996752 TI - Identification of multiphasic and weak-link structures in a (La0.94Sr0.06)2CuO4 single crystal by magnetically modulated resistance. PMID- 9996753 TI - First-principles treatment of disorder effects in complex alloys: A study of BaxK1-xBiO3 and BaPb1-xBixO3. PMID- 9996754 TI - Deviations from planarity of copper-oxygen sheets in Ca0.85Sr0.15CuO2. PMID- 9996755 TI - Quasihole excitation in a quantum antiferromagnet: Variational Monte Carlo calculation. PMID- 9996756 TI - Effects of Fe and Zn substitution upon superconductivity in YBa2Cu4O8. PMID- 9996758 TI - Collective flux creep in high-Tc superconductors. PMID- 9996757 TI - Superconductivity and antiferromagnetism in the Cu(2) planes of YBa2Cu3O7Hx. PMID- 9996759 TI - Far-infrared transmittance and reflectance studies of oriented YBa2Cu3O7- delta thin films. PMID- 9996760 TI - Microwave transmission and harmonic generation in granular high-Tc superconducting films: Evidence for viscous flux motion and weak links. PMID- 9996761 TI - High-temperature equilibrium study of the oxygen-site occupancy in YBa2Cu3O7- delta by positron annihilation. PMID- 9996762 TI - Thermal activation of vortex motion in YBa2Cu3O7- delta films at low temperatures. PMID- 9996763 TI - Finite-cluster study of superconductivity in the two-dimensional molecular crystal model. PMID- 9996764 TI - Positron trapping at defects in copper oxide superconductors. PMID- 9996765 TI - Melting of a flux-line fluid confined by CuO2 planes: Lindemann-criterion failure. PMID- 9996766 TI - Instabilities of the Fermi-liquid and staggered flux phases in the large-N t-J model. PMID- 9996768 TI - Magnetic transitions in Nd2NiO4. PMID- 9996767 TI - Oxygen-loss effects on superconductivity of Bi2Sr2CaCu2Oy system. PMID- 9996769 TI - Initial magnetization and coupling nature of the high-Tc grains in Bi-Pb-Sr-Ca-Cu O. PMID- 9996770 TI - Magnetothermal behavior of the two-dimensional triangular-lattice compounds RCuO2 PMID- 9996772 TI - Modulated microwave absorption of a superconducting loop with two nonidentical Josephson junctions. PMID- 9996771 TI - 17O nuclear-magnetic-resonance spin-lattice relaxation and Knight-shift behavior in bismuthate, plumbate, and cuprate superconductors. PMID- 9996773 TI - High-power, pulsed-microwave measurements of critical currents in thin films of Y Ba-Cu-O and Nb. PMID- 9996775 TI - Optical-phonon study of single crystals of various layered cuprates and related materials: Evidence of unique electron-phonon coupling in the CuO2 plane. PMID- 9996774 TI - Comparison of paramagnetic- and nonmagnetic-impurity effects on superconductivity in Nd1.85Ce0.15CuO4. PMID- 9996776 TI - Temperature- and field-dependent I-V characteristics of an Ag/YBa2Cu3O7- delta fiber. PMID- 9996777 TI - Optical, magnetic, and single-particle excitations in the multiband Hubbard model for cuprate superconductors. PMID- 9996778 TI - Antiferromagnetic spin-fluctuation effects on quasiparticle damping and superconductivity in high-Tc materials. PMID- 9996779 TI - Observation of a vortex-glass phase in polycrystalline YBa2Cu3O7-x in a magnetic field. PMID- 9996780 TI - Electronic states in rare-earth 1:2:3 oxides: Photoemission and Raman studies. PMID- 9996781 TI - Magnetic and elastic properties of La2NiO4+x. PMID- 9996782 TI - Random-field-like disorder and magnetic-field effects in unconventional superconductors. PMID- 9996783 TI - Critical-temperature inhomogeneities and resistivity rounding in copper oxide superconductors. PMID- 9996784 TI - Suppression of superconductivity in Gd1-xPrxBa2Cu3O7-y and R0.8Pr0.2Ba2Cu3O7-y systems. PMID- 9996785 TI - Infrared-absorption and photoinduced-absorption spectroscopy of semiconducting YBa2Cu3 AO6+x (A=16 and 18; 0 <= x <= 0.3). PMID- 9996787 TI - Destruction of superconductivity in the Bi2Sr2Ca1-xGdxCu2-yLiyO8+d system. PMID- 9996786 TI - Absorption and photoinduced-absorption spectroscopy in semiconducting YBa2Cu3O6+x. PMID- 9996789 TI - Iron and chromium monolayer magnetism in noble-metal hosts: Systematics of local moment variation with structure. PMID- 9996788 TI - Small ab initio Cu(II) oxide cluster model with localized states and strong screening effects accompanying ionization. PMID- 9996790 TI - Comparison of cluster algorithms for two-dimensional Potts models. PMID- 9996791 TI - Singlet quantum Hall effect and Chern-Simons theories. PMID- 9996792 TI - Phase boundaries near critical end points. II. General spherical models. PMID- 9996794 TI - Structure of hard spheres in contact with a spherical wall. PMID- 9996793 TI - Electronic structure and binding energies of aluminum clusters. PMID- 9996795 TI - State counting and low-temperature series. PMID- 9996796 TI - Influence of conduction electrons on impurity tunneling in small metal particles at low temperatures. PMID- 9996797 TI - Coherent propagation of waves in intrinsically nonuniform random media. PMID- 9996798 TI - Probing the metal-nonmetal transition in thin metal overlayers using resonant photoemission. PMID- 9996799 TI - Investigation of the incommensurate transition of sodium nitrite by the neutron spin-echo technique. PMID- 9996800 TI - Ethylene on graphite: A low-energy electron-diffraction study. PMID- 9996801 TI - Spiral phase in a doped antiferromagnet. PMID- 9996802 TI - Microscopic theory of spin arrangements and spin waves in very thin ferromagnetic films. PMID- 9996803 TI - Directed paths in a random potential. PMID- 9996804 TI - Nonlinear dynamics in a double-chain model of DNA. PMID- 9996805 TI - Impossibility of continuous deterministic phasons in octagonal quasicrystals. PMID- 9996806 TI - Screened Anderson model. PMID- 9996807 TI - Anyons on a torus: Braid group, Aharonov-Bohm period, and numerical study. PMID- 9996809 TI - Permeability and permittivity spectra of granular materials. PMID- 9996808 TI - Acoustic-wave localization in the presence of shear resonances. PMID- 9996811 TI - Concentration dependence of the random-field-crossover scaling in FexZn1-xF2. PMID- 9996810 TI - Zero-temperature properties of the quantum XY model with anisotropy. PMID- 9996812 TI - Calculation of electronic and magnetic structures of Fe/Cr, Co/Cr, and Ni/Cr multilayers. PMID- 9996814 TI - Spiral antiferromagnetism and the doping-induced closure of the Mott-Hubbard gap. PMID- 9996813 TI - Spectral structure of two-dimensional Fibonacci quasilattices. PMID- 9996815 TI - Magnetism in amorphous transition metals. PMID- 9996816 TI - Adaptive phase formation in martensitic transformation. PMID- 9996818 TI - Quantum vector spin glasses with random Dzyaloshinsky-Moriya interactions. PMID- 9996817 TI - Variational estimation of the ground-state energy of the frustrated Heisenberg model. PMID- 9996819 TI - Nonlinear sigma model for localization in superconductors: Role of order parameter phase fluctuations. PMID- 9996820 TI - Generalized Laplacian roughening model on a triangular lattice. PMID- 9996821 TI - Spectral function of a single hole in a two-dimensional quantum antiferromagnet. PMID- 9996823 TI - Low-temperature heat capacity and magnetic properties of the RNiX2 compounds (R=La, Ce; X=Si, Ge, Sn). PMID- 9996822 TI - Three-dimensional axial next-nearest-neighbor Ising model: A series investigation. PMID- 9996824 TI - Green's functions, density of states, and dynamic structure factor for a general one-dimensional quasicrystal. PMID- 9996825 TI - Electron transport in disordered systems: A nonequilibrium quantum-molecular dynamics approach. PMID- 9996826 TI - Phonon dispersion of the bcc phase of group-IV metals. I. bcc titanium. PMID- 9996827 TI - Phonon dispersion of the bcc phase of group-IV metals. II. bcc zirconium, a model case of dynamical precursors of martensitic transitions. PMID- 9996828 TI - Phonon dispersion of the bcc phase of group-IV metals. III. bcc hafnium. PMID- 9996830 TI - Power dissipation in random resistor networks with a broad distribution of conductivities. PMID- 9996829 TI - Static and dynamical correlations in a spin-1/2 frustrated antiferromagnet. PMID- 9996831 TI - Transition from surface-spin to bulk-spin relaxation in an S=1/2 nearest-neighbor XY chain at infinite temperature. PMID- 9996832 TI - Raman spectroscopy of incommensurate Ba2NaNb5O15. PMID- 9996833 TI - Effect of composition on Curie temperature, magnetic moment, and high-field susceptibility of amorphous Fe90-xMxZr10 (M=V, Cr, Mn, Co, Ni, Cu, Si, and B) alloys. PMID- 9996835 TI - Two-dimensional mixed crystals. PMID- 9996834 TI - Group-theoretical methods for obtaining distortions in crystals: Applications to vibrational modes and phase transitions. PMID- 9996837 TI - Uniaxial-strain dependence of shear-modulus anomalies in TaS3. PMID- 9996836 TI - Gapless boundary excitations in the quantum Hall states and in the chiral spin states. PMID- 9996838 TI - Fast oscillations and the high-field phase boundary in (TMTSF)2ClO4 (where TMTSF represents tetramethyltetraselenafulvalene). PMID- 9996839 TI - Enhanced temperature-dependent magnetoresistivity of Fe/Cr superlattices. PMID- 9996840 TI - Coexistence of magnetic order and heavy-fermion paramagnetism in Ce5Sn3. PMID- 9996841 TI - Exact time-dependent propagation of vacancy motion in the t-J limit of the two dimensional Hubbard Hamiltonian. PMID- 9996842 TI - Magnetic susceptibility of YbN. PMID- 9996843 TI - Temperature dependence of the first sharp diffraction peak in vitreous silica. PMID- 9996845 TI - Critical behavior of the thermopower near the metal-insulator transition. PMID- 9996844 TI - Quantum Monte Carlo study of the spin-1/2 Heisenberg model. PMID- 9996846 TI - Ferromagnetic properties of the degenerate semiconductor Pb0.20Sn0.72Mn0.08Te. PMID- 9996848 TI - Hysteresis at the spin-flop transition in the antiferromagnets K2Fe(Cl1-xBrx)5 PMID- 9996847 TI - Magnon damping, spin stiffness, and dynamic scaling in the two-dimensional quantum Heisenberg ferromagnet at low temperatures. PMID- 9996849 TI - Defect-induced condensation and central peak at structural transitions. PMID- 9996850 TI - Plutonium chalcogenides: Intermediate valence and electronic structure. PMID- 9996851 TI - Susceptibility and surface magnetostatic modes for the spiral and cone states of rare-earth magnets. PMID- 9996852 TI - Influence of defects on the incommensurate modulation in irradiated Ba2NaNb5O15. PMID- 9996854 TI - Structural phase transition in the nonlinear-polarizability shell model. PMID- 9996853 TI - Incommensurate phases in betaine calcium chloride dihydrate. PMID- 9996855 TI - Fracton density of states by the maximum-entropy method. PMID- 9996856 TI - Phase boundaries near critical end points. I. Thermodynamics and universality. PMID- 9996857 TI - Pressure-induced phase transitions in silver halides. PMID- 9996858 TI - Universal family of kink-bearing models reconstructed from a Poschl-Teller scattering potential. PMID- 9996859 TI - Soliton excitations in the alternating ferromagnetic Heisenberg chain. PMID- 9996862 TI - Series expansions for the Ising spin glass in general dimension. PMID- 9996861 TI - Asymptotic and leading correction-to-scaling specific-heat critical exponents and amplitudes for quench-disordered ferromagnets from resistivity measurements. PMID- 9996860 TI - Geometry-controlled conserving approximations for the t-J model. PMID- 9996863 TI - Conductivity and 1/f-noise study of three-component random resistor networks. PMID- 9996864 TI - Scaling of the field effect on the magnetic relaxation about the Curie point of EuS. PMID- 9996865 TI - Phase diagram for a generalized fully frustrated triangular XY model. PMID- 9996866 TI - Correlation corrections to the conductivity of one-dimensional disordered hopping models. PMID- 9996867 TI - Electronic structure of the ordered phases of Pt-Fe alloys. PMID- 9996868 TI - Resonant zero-sound exchange in the 1/N expansion of the infinite-U Hubbard model. PMID- 9996869 TI - Orthogonality exponent and the friction coefficient of an electron gas. PMID- 9996870 TI - Symmetry of composite crystals. PMID- 9996872 TI - Quantum Hall effect in quasi-one-dimensional conductors. PMID- 9996871 TI - Scaling theory for the optical properties of semicontinuous metal films. PMID- 9996873 TI - Linear polarization of radiation from planar channeled electrons and positrons. PMID- 9996875 TI - Substitution position of the impurity ion Mn2+ in LiNbO3. PMID- 9996874 TI - Direct measurement of fixed-charge stopping power for 32-MeV 3He1+ in a charge state nonequilibrium region. PMID- 9996876 TI - Conduction mechanism in YBa2Cu3Oz in the normal state. PMID- 9996877 TI - Temperature dependence of the phonon structure in the high-temperature superconductor Bi2Sr2CaCu2O8 studied by infrared reflectance spectroscopy. PMID- 9996878 TI - Magnetic-field influence on polaronic electrons on liquid-helium films. PMID- 9996879 TI - Monte Carlo study of U(1) lattice gauge Higgs model of high-Tc superconductivity. PMID- 9996880 TI - Superconductivity in the mean-field anyon gas. PMID- 9996881 TI - Cubic phase in the Y-Ba-Cu-O system. PMID- 9996882 TI - Pairing of holes in a tight-binding model with repulsive Coulomb interactions. PMID- 9996883 TI - Magnetic-field dependence of the ac susceptibility in granular YBa2Cu3O7: Data and models. PMID- 9996885 TI - Electron paramagnetic resonance of Cu2+ ions in the tetragonal perovskite LaCuO3- delta. PMID- 9996884 TI - Circular dichroism observed in bismuthate superconductors. PMID- 9996887 TI - Numerical analysis of the anomalies in the thermal conductivity of the high-Tc superconductors YBa2Cu3O7-x. PMID- 9996886 TI - Electronic disorder, gap states, orbital depairing, and dynamics of percolative superconductors near Tc. PMID- 9996888 TI - Irreversibility-line study in the polycrystalline Bi2Sr2CaCu2O8 superconductor. PMID- 9996890 TI - Spin-Peierls transition, flux phase, and anyon superconductivity. PMID- 9996889 TI - Effect of hopping between oxygen atoms on the metal-insulator transition in CuO2 planes of high-Tc superconductors. PMID- 9996891 TI - Observation of a birefringence anomaly at the 93-K phase transition in K2SeO4. PMID- 9996892 TI - Quantum vector spin-glass models in an applied field. PMID- 9996893 TI - Shrinking and freezing of embedded domains. PMID- 9996894 TI - Phase separation in the Hubbard model. PMID- 9996895 TI - Magnetic dynamics in La2CuO4 with interlayer coupling and anisotropy gaps. PMID- 9996896 TI - Comment on "Low-temperature properties of the Hubbard chain with an attractive interaction" PMID- 9996897 TI - Reply to "Comment on 'Low-temperature properties of the Hubbard chain with an attractive interaction' " PMID- 9996899 TI - Erratum: Phenomenological theory of longitudinal spin fluctuations in CsNiCl3 PMID- 9996898 TI - Comment on "Low-temperature properties of quantum Heisenberg helimagnets" PMID- 9996900 TI - Magnetic behavior of 1,3- PMID- 9996901 TI - Incident-beam enhancements of Auger electron scattering. PMID- 9996902 TI - Thermal depinning of the modulation wave in the presence of random impurities. PMID- 9996903 TI - Quantized Hall effect in the organic superconductor (TMTSF)2ReO4 (TMTSF=tetramethyltetraselenafulvalinium). PMID- 9996904 TI - Spin excitations and the electronic specific heat of URu2Si2. PMID- 9996905 TI - Charge-transfer polarons and excitons. PMID- 9996906 TI - Anisotropic energy dissipation in high-Tc ceramic superconductors: Local-field effects. PMID- 9996907 TI - Anisotropic vortex cross-flux effects in grain-oriented YBa2Cu3O7. PMID- 9996908 TI - Hall-effect studies in YBa2Cu3O7/PrBa2Cu3O7 superlattices. PMID- 9996909 TI - Magnetic-ordering, hyperfine, and linear contributions to the low-temperature specific heat of (Y1-xPrx)Ba2Cu3O7- delta. PMID- 9996910 TI - Bi-Sr-Ca-Cu-O thin-film energy gap as a function of temperature and force applied to squeezable-electron-tunneling junctions. PMID- 9996911 TI - Epitaxial intercalation of the Bi-Sr-Ca-Cu-O superconductor series. PMID- 9996912 TI - X-ray-photoemission-spectroscopy study of the surface deterioration of Bi2Sr2CaCu2O8 and Bi1.7Pb0.3Sr2CaCu2O8 single crystals at 26 K. PMID- 9996913 TI - Theory of angle-resolved photoemission from the cuprate superconductors. PMID- 9996914 TI - Thermoelectric power of the (Eu,Ce)4(Ba,Eu)4Cu6Oy phase and the T* phase: Comparison between superconducting and nonsuperconducting compounds. PMID- 9996915 TI - Determination of the spatial length scale of the magnetic-field distribution in the YBa2Cu3O7 ceramic by surface EPR. PMID- 9996916 TI - Landau-level spin waves and Skyrmion energy in the two-dimensional Heisenberg antiferromagnet. PMID- 9996917 TI - Fast algorithm to calculate exact geometrical factors for the q-state Potts model. PMID- 9996919 TI - Anisotropy-driven long-range order in ultrathin ferromagnetic films. PMID- 9996918 TI - Monte Carlo simulation of hard-sphere fluid and solid in a confined geometry. PMID- 9996920 TI - Monte Carlo study of frustrated XY models on a triangular and square lattice. PMID- 9996921 TI - Critical amplitude ratios for critical wetting in three dimensions: Observation of nonclassical behavior in the Ising model. PMID- 9996922 TI - Motion of kinks in the ac-driven damped Frenkel-Kontorova chain. PMID- 9996924 TI - Noise and crossover exponent in the two-component random resistor network. PMID- 9996923 TI - Raman fingerprint of orientational freezing in mixed molecular crystals. PMID- 9996925 TI - Coverage dependence of surface optical second-harmonic generation from CO/Ni(110): Investigation with a nonlinear-interference technique. PMID- 9996927 TI - Equivalence of the multilead approach to dephasing and the self-consistent Born approximation. PMID- 9996926 TI - Influence of surface roughness on the conductivity of metallic and semiconducting quasi-two-dimensional structures. PMID- 9996928 TI - Measurement of the binding energy of kink-site atoms of metals and alloys. PMID- 9996930 TI - Generalized expression for the tunneling current in scanning tunneling microscopy. PMID- 9996929 TI - Bonding energetics of metals: Explanation of trends. PMID- 9996932 TI - Gradient-corrected density functionals: Full-potential calculations for iron. PMID- 9996931 TI - Multichannel, multiprobe Landauer formula in the presence of a uniform magnetic field. PMID- 9996933 TI - Stable one-component quasicrystals. PMID- 9996934 TI - Crystalline and glassy phases of transition-metal-metalloid systems. PMID- 9996935 TI - Development of an N-body interatomic potential for hcp and bcc zirconium. PMID- 9996936 TI - Effect of atomic-structure modulation on the ionic conductivity of a Na4.6FeP2O8.6F0.4 single crystal. PMID- 9996937 TI - Persistence of atomic magnetism in the paramagnetic phase of chromium. PMID- 9996939 TI - Nuclear-spin relaxation and spin-wave collective modes in a disordered two dimensional electron gas. PMID- 9996938 TI - Magnetoresistance in quantum wires: Boundary-roughness scattering. PMID- 9996940 TI - Defects in hydrogenated amorphous silicon-germanium alloys studied by photomodulation spectroscopy. PMID- 9996941 TI - Theory of optical anisotropy in quantum-well-wire arrays with two-dimensional quantum confinement. PMID- 9996942 TI - Semiclassical small-polaron hopping in a generalized molecular-crystal model. PMID- 9996943 TI - Hydrodynamic theory of magnetoplasmons in a modulated two-dimensional electron gas. PMID- 9996944 TI - Evidence for an electron-hole plasma in the photoluminescence spectra of insulating InSb at very low pump intensities. PMID- 9996945 TI - First-order Raman spectrum of diamond at high temperatures. PMID- 9996946 TI - Theory of Schottky-contact formation on GaAs(110). PMID- 9996947 TI - Relaxation of icosahedral-cage silicon clusters via tight-binding molecular dynamics. PMID- 9996948 TI - Anomalous galvanomagnetic behavior of orthorhombic layered GeS single crystals. PMID- 9996949 TI - Elementary excitation spectrum of one-dimensional electron systems in confined semiconductor structures: Zero magnetic field. PMID- 9996950 TI - Two-dimensional electron gas in GaAs/Al1-xGaxAs heterostructures: Effective mass. PMID- 9996951 TI - Temperature and doping-concentration dependence of the oscillatory properties of the photoreflectance spectra from GaAs grown by molecular-beam epitaxy. PMID- 9996952 TI - Zone-folding effect in short-period (GaAs)n/(AlAs)n superlattices with n in the range 3-15. PMID- 9996953 TI - Potential-barrier measurements at clustered metal-semiconductor interfaces. PMID- 9996954 TI - Multiphonon resonant Raman scattering in short-period GaAs/AlAs superlattices. PMID- 9996955 TI - Minimum overlayer thickness for interface formation: An experimental study of the Cu/Ag/Cu(111) system. PMID- 9996956 TI - Low-temperature electrical conductivity of highly conducting polyacetylene in a magnetic field. PMID- 9996957 TI - Carrier hopping capture in semiconductors. PMID- 9996958 TI - Structural and electronic properties of the Bi/GaP(110) interface. PMID- 9996959 TI - Optical phonons in GaAs/AlAs quantum wires. PMID- 9996961 TI - Structural model for pseudobinary semiconductor alloys. PMID- 9996960 TI - Fine structure of hopping conductance fluctuations in finite-size semiconductors. PMID- 9996962 TI - Modulated photoabsorption in strained Ga1-xInxAs/GaAs multiple quantum wells. PMID- 9996963 TI - Initial stages of oxidation of Si(111) with condensed O2 and N2O at 20 K. PMID- 9996964 TI - Dynamic response of quantum dots. PMID- 9996965 TI - Two-photon-absorption spectrum of poly(di-n-hexylsilane) films. PMID- 9996966 TI - Atomic and electronic structure of CaSi2/Si interfaces. PMID- 9996967 TI - Structural study of evaporated amorphous As4S4 films by x-ray-absorption fine structure. PMID- 9996968 TI - Sulfur deficiency in iron pyrite (FeS2-x) and its consequences for band-structure models. PMID- 9996969 TI - Pseudopotential Hartree-Fock study of seventeen III-V and IV-IV semiconductors. PMID- 9996970 TI - Exciton-binding-energy maximum in Ga1-xInxAs/GaAs quantum wells. PMID- 9996971 TI - Temperature dependence of the dielectric function and the interband critical point parameters of AlxGa1-xAs. PMID- 9996972 TI - Effects of coimplantation of silicon and nitrogen on structural defects and Si-N bond formation in silica glass. PMID- 9996973 TI - Satellite structure in the photoemission spectra of MnO(100). PMID- 9996975 TI - Luminescence of F+ centers in CaO crystals under pulsed-laser excitation. PMID- 9996976 TI - Electrical transport of mixed (Na+,Ba2+) beta "-alumina. PMID- 9996974 TI - Influence of d orbitals on the nonlinear optical response of transparent transition-metal oxides. PMID- 9996978 TI - X-ray study of the intercalant distribution in mixed alkyl ammonium pillared clay. PMID- 9996977 TI - Cation-ligand hybridization for stoichiometric and reduced TiO2 (110) surfaces determined by resonant photoemission. PMID- 9996979 TI - Defect structures and the MgO-doping-level-threshold effect on the optical absorption of reduced MgO-doped lithium niobate. PMID- 9996980 TI - Many-body properties calculated from the Kohn-Sham equations in density functional theory. PMID- 9996981 TI - Quantum tunneling of surface-state electrons in time-dependent fields. PMID- 9996983 TI - Charge-density excitations in the fractional quantized Hall effect in superlattices. PMID- 9996982 TI - Photoluminescence excitation spectroscopy of remotely doped wide parabolic GaAs/AlxGa1-xAs quantum wells. PMID- 9996985 TI - Lifetime of the Stark resonant level in double-barrier structures. PMID- 9996984 TI - Tunneling and anticrossing of edge magnetoplasmons in a quantum-dot superlattice. PMID- 9996986 TI - Phonon-mediated indirect interactions between adatoms on surfaces: O adatoms on Si(100). PMID- 9996987 TI - Coherent time-resolved investigation of LO-phonon dynamics in GaAs. PMID- 9996988 TI - Structure of single-molecular-layer MoS2. PMID- 9996989 TI - Additional evidence concerning the valence-band offset in HgTe/CdTe. PMID- 9996990 TI - Erratum: Electron band structure of a rare-earth metal: Tb(0001) PMID- 9996991 TI - Surface Fermi contours and phonon anomalies on Pt(111). PMID- 9996992 TI - Semiclassical theory of shot noise and its suppression in a conductor with deterministic scattering. PMID- 9996993 TI - Hartree-Fock core local-density-approximation valence pseudopotentials. PMID- 9996994 TI - Anomalous temperature dependence of the phase-coherence length for inhomogeneous gold films. PMID- 9996995 TI - Energy and angular distributions of excited rhodium atoms ejected from the rhodium (100) surface. PMID- 9996996 TI - Electronic properties of quantum-dot superlattices. PMID- 9996997 TI - Effects of surface band bending on low-energy photon-induced oxidation of GaAs(110). PMID- 9996998 TI - Spatial potential distribution in GaAs/AlxGa1-xAs heterostructures under quantum Hall conditions studied with the linear electro-optic effect. PMID- 9996999 TI - Electrical transport in narrow-miniband semiconductor superlattices. PMID- 9997000 TI - Self-consistent model of magnetoplasmons in quantum dots with nearly parabolic confinement potentials. PMID- 9997001 TI - Time dependence of photovoltaic shifts in photoelectron spectroscopy of semiconductors. PMID- 9997002 TI - Negative-U, off-center OAs in GaAs and its relation to the EL3 level. PMID- 9997003 TI - Extreme g-factor anisotropy induced by strain. PMID- 9997004 TI - Measurement of positron mobility in Si at 30-300 K. PMID- 9997005 TI - Voltage-probe-controlled breakdown of the quantum Hall effect. PMID- 9997006 TI - Surface-induced optical anisotropy of the Si(110) surface. PMID- 9997007 TI - Deep center in Al0.3Ga0.7As. PMID- 9997008 TI - Static lattice distortions and the structure of Au/Si(111)-(5 x 1): An x-ray diffraction study. PMID- 9997009 TI - Fermi-edge singularity and band-filling effects in the luminescence spectrum of Be- delta -doped GaAs. PMID- 9997011 TI - Formation of extended hydrogen complexes in silicon. PMID- 9997010 TI - Observation of Franz-Keldysh oscillations in the stress-modulated spectra of (001) n-type GaAs. PMID- 9997012 TI - Quasiparticle surface band structure and photoelectric threshold of Ge(111)-2 x 1. PMID- 9997013 TI - Investigation of the electronic structure in Cu-Au I using x-ray-photoelectron spectroscopy. PMID- 9997014 TI - Relative stability of the Al12W structure in Al-transition-metal compounds. PMID- 9997016 TI - Structure and morphology of Au grown on Ag(110). PMID- 9997015 TI - Anomalous dynamical behavior of the Cu(110) surface. PMID- 9997017 TI - Theory of charge-density-wave tunneling. PMID- 9997018 TI - He-diffraction studies of the low-coverage (1 x 3)-H and the saturation (1 x 1) 2H phases on Rh(110). PMID- 9997020 TI - Vibrational properties of the clean reconstructed W(100) surface. PMID- 9997019 TI - Atoms embedded in an electron gas: Beyond the local-density approximation. PMID- 9997021 TI - Inelastic scattering of x rays at intermediate momentum transfers. PMID- 9997022 TI - Phase stability in Ti-V and Ti-Cr alloys: A theoretical investigation. PMID- 9997023 TI - Quantum magnetoresistance fluctuations in an amorphous metal. PMID- 9997024 TI - Photoemission-spectroscopy investigation of the chemical-pressure effect in Yb1 xMxAl2 (M=Ca,Sc). PMID- 9997026 TI - Numerical modeling of superlattice x-ray-scattering intensities. PMID- 9997025 TI - Azimuthal dependence of the near-edge x-ray-absorption fine structure from Ni(110)c(2 x 2)-S at the S K edge. PMID- 9997027 TI - Magnetotransport at the metal-insulator transition in fluorine-intercalated graphite fibers. PMID- 9997029 TI - Interaction of alkali metals with Si(001)-2 x 1. PMID- 9997028 TI - Optical dispersion relations in amorphous semiconductors. PMID- 9997030 TI - Modulation spectroscopy of the complex photoluminescence band of Ga0.7Al0.3As:Si. PMID- 9997031 TI - Subband effects on electron transport in quasi-one-dimensional electron systems. PMID- 9997032 TI - Surface-shifted core levels in Mo3Si (100) and (110). PMID- 9997034 TI - Polariton-impurity interactions and photoconductivity in CdTe studied by cyclotron-resonance-excitation spectroscopy. PMID- 9997033 TI - Alloy-disorder-induced intervalley coupling. PMID- 9997035 TI - Antimony-doping effect on the ac conductivity of the amorphous Se-Te system. PMID- 9997036 TI - Hole-state reversal and the role of residual strain in (In,Ga)As-GaAs superlattices. PMID- 9997037 TI - Exciton spectra and anisotropic Zeeman effect in PbI2 at high magnetic fields up to 40 T. PMID- 9997038 TI - Collective interactions in a quantum well: The inclusion of nonlocal exchange. PMID- 9997039 TI - Electronic structure and core excitons in AlSb as studied by soft-x-ray spectroscopy. PMID- 9997040 TI - Lattice dynamics of isolated nitrogen in synthetic diamond. PMID- 9997041 TI - X-ray-diffraction measurement of interface structure in GaAs/Si(001). PMID- 9997043 TI - Terahertz-frequency-resolved transient conductivity of nonthermal electrons photoexcited in GaAs. PMID- 9997042 TI - Quantum ballistic and adiabatic electron transport studied with quantum point contacts. PMID- 9997045 TI - Band dispersion in the recursion method. PMID- 9997044 TI - Exciton dispersion in multiple quantum wells and superlattices: An additional contribution to the linewidth. PMID- 9997046 TI - Theoretical approach to delta doping of GaAs with In. PMID- 9997047 TI - Optical second-order susceptibility of GaAs/AlxGa1-xAs asymmetric coupled-quantum well structures in the exciton region. PMID- 9997048 TI - Virtual photoconductivity due to intense optical radiation transmitted through a semiconductor. PMID- 9997049 TI - Raman scattering in diamond up to 1900 K. PMID- 9997051 TI - Quasi-parity-conserving octahedral model for (H,Be) and (D,Be) tunneling complexes in silicon. PMID- 9997050 TI - Formation energies, electronic structure, and hyperfine fields of chalcogen point defects and defect pairs in silicon. PMID- 9997053 TI - Effect of electron-phonon coupling on the hopping rate of charged particles in a superlattice. PMID- 9997052 TI - Nuclear-magnetic-resonance studies of strain in isovalently doped GaAs. PMID- 9997054 TI - Electronic excitations of poly(methylphenylsilane) films. PMID- 9997055 TI - Analytical model of high-frequency resonant tunneling: The first-order ac current response. PMID- 9997056 TI - Electronic structure of CrSi2 and related refractory disilicides. PMID- 9997057 TI - Singularities in the optical spectra of a system involving a Fermi sea of electrons and a localized hole: A method for obtaining many-body wave functions. PMID- 9997058 TI - Measurement of the exciton-formation time and the electron- and hole-tunneling times in a double-quantum-well structure. PMID- 9997059 TI - Simulating diffusion on Si(001) 2 x 1 surfaces using a modified interatomic potential. PMID- 9997060 TI - Resonant-Raman-scattering and photoluminescence studies in glass-composite and colloidal CdS. PMID- 9997061 TI - Excitonic absorption edge in alkali halides and the Urbach-Martienssen rule studied by three-photon difference-frequency generation. PMID- 9997062 TI - Electronic structure of fluorite-type compounds and mixed crystals. PMID- 9997063 TI - Interatomic potential for directional bonding: The rotated-second-moment approximation. PMID- 9997064 TI - Interband contribution to the long-wavelength damping of the surface plasmon. PMID- 9997065 TI - Angle-resolved x-ray-photoemission study of the surface disordering of Pb(100). PMID- 9997066 TI - N-induced (2 x 3) reconstruction of Cu(110): Evidence for long-range, highly directional interaction between Cu-N-Cu bonds. PMID- 9997067 TI - Palladium-graphite interaction potentials based on first-principles calculations. PMID- 9997068 TI - Exciton binding energy in GaAs/AlxGa1-xAs multiple quantum wells. PMID- 9997069 TI - Quantum coherence effects and field-induced localization in InSb. PMID- 9997070 TI - Energy-band structure for strained p-type Si1-xGex. PMID- 9997071 TI - Breakdown of quantized conductance in point contacts calculated using realistic potentials. PMID- 9997072 TI - Stability of the Frohlich bipolaron in two and three dimensions. PMID- 9997073 TI - Resonant transmission of acoustic phonons in multisuperlattice structures. PMID- 9997074 TI - Raman scattering by LO phonons in (GaAs)n1/(AlAs)n2 ultrathin-layer superlattices. PMID- 9997075 TI - Interaction of quasiparticles in the 1/3 quantum Hall state and hierarchical estimates of the energy of daughter states. PMID- 9997076 TI - Stimulated-picosecond-photon-echo studies of localized exciton relaxation and dephasing in GaAs/AlxGa1-xAs multiple quantum wells. PMID- 9997077 TI - Polaronlike vibrational bands of molecular crystals with one-dimensional hydrogen bond chains: N-methylacetamide. PMID- 9997078 TI - Comment on "Temperature-induced structural phase transition in CaBr2 studied by Raman spectroscopy" PMID- 9997079 TI - Reply to "Comment on 'Temperature-induced structural phase transition in CaBr2 studied by Raman spectroscopy' " PMID- 9997080 TI - Electronic density of states of AlxGa1-xAs. PMID- 9997082 TI - Channeling radiation and coherent bremsstrahlung for simple lattices: A three dimensional approach. PMID- 9997081 TI - Measurement of Fermi-surface distortion in double quantum wells from in-plane magnetic fields. PMID- 9997083 TI - Molecular-dynamics simulation of prompt sputtering of a molecular solid at high excitation densities. PMID- 9997084 TI - Positron-electron annihilation in the proximity of a second electron in a dense medium. PMID- 9997085 TI - Two-pulse and stimulated nuclear-quadrupole-resonance echoes in YAlO3:Pr3+ PMID- 9997086 TI - Secondary electrons induced by fast ions under channeling conditions. I. Production and emission of secondary electrons. PMID- 9997087 TI - Secondary electrons induced by fast ions under channeling conditions. II. Screening of fast heavy ions in solids. PMID- 9997088 TI - Accumulated photon echo in ruby under hydrostatic pressure: Ground-state splitting and spontaneous decay of 2A-bar(2E). PMID- 9997089 TI - NMR determination of order parameters in the quadrupolar glasses Na(CN)xCl1-x and NaxK1-xCN. PMID- 9997090 TI - Photoacoustic and luminescence spectroscopy of benzil crystals. PMID- 9997091 TI - Quantum optics of localized light in a photonic band gap. PMID- 9997092 TI - Theory of NMR in heavy-fermion compounds using the slave-boson technique. PMID- 9997093 TI - Bifurcation and chaos in a dc-driven long annular Josephson junction. PMID- 9997094 TI - Superconducting optical conductivity for arbitrary temperature and mean free path. PMID- 9997096 TI - Vortex-defect interactions in Josephson-junction arrays. PMID- 9997095 TI - Magnetic excitations in the heavy-fermion superconductor URu2Si2. PMID- 9997098 TI - Third-sound wave in superfluid films as a probe of interface exchanges and film entropy evaluation. PMID- 9997097 TI - Aziz fermions and liquid 3He. PMID- 9997099 TI - Nucleation and motion of an isolated Abrikosov vortex. PMID- 9997100 TI - Stability of antipolar fluxons in an infinitely long Josephson junction with shunt loss, surface-impedance loss, and bias current. PMID- 9997101 TI - Probability of quasiparticle self-trapping due to localized energy deposition in nonequilbrium tunnel-junction detectors. PMID- 9997102 TI - Quantitative studies of nonlinear second sound in superfluid 4He. PMID- 9997103 TI - Two-component Fermi liquids and the induced-interaction model. PMID- 9997104 TI - Collective excitations in the A phase of 3He. PMID- 9997105 TI - Macroscopic tunneling in Josephson junctions with two-state fluctuators. PMID- 9997106 TI - Self-consistent theory of heavy-fermion alloys. PMID- 9997107 TI - Spin excitations in a quantum antiferromagnet with magnetic impurities and vacancies. PMID- 9997108 TI - Anharmonic phonons and the isotope effect in superconductivity. PMID- 9997109 TI - Anisotropic resistivity and paraconductivity of Tl2Ba2CaCu2O8 single crystals. PMID- 9997110 TI - Systematic variation of transport and thermodynamic properties with degree of reduction in Nd1.85Ce0.15CuO4- delta. PMID- 9997111 TI - Nonmonotonic resistivity transitions in granular superconducting ceramics. PMID- 9997112 TI - Phase diagrams of the two-dimensional Hubbard and t-J models by a variational Monte Carlo method. PMID- 9997113 TI - Density of states in La2CuO4+y. PMID- 9997114 TI - Two superconducting gaps and electron-phonon coupling in YBa2Cu4O8. PMID- 9997115 TI - Far-infrared absorption by bulk high-Tc superconductors using an optically pumped CH3OH laser. PMID- 9997117 TI - Effects of Cu substitution by Fe on the magnetic properties of YBa2Cu3O7-y single crystals. PMID- 9997116 TI - Magnetic properties of antiferromagnets with mobile vacancies. PMID- 9997118 TI - Hole filling and hole creation in the superconducting compounds Bi2Sr2-xRxCuO6+y (R=La, Pr, Nd, and Sm). PMID- 9997119 TI - Anisotropic superconducting properties of aligned (Bi,Pb)2Can-1Sr2CunO2n+4+ delta powders (n=1,2,3) with Tc=32, 94, and 110 K. PMID- 9997120 TI - Microstructure of ultrathin films of YBa2Cu3O7- delta on MgO. PMID- 9997121 TI - Positron-annihilation studies on the Bi-Sr-Ca-Cu-O superconductor. PMID- 9997123 TI - Dislocation-mediated flux creep in Bi2Sr2CaCu2O8+ delta. PMID- 9997122 TI - Effects of nonstoichiometry, ordering, and Bi substitution with Pb in Bi2Sr2CaCu2O8. PMID- 9997124 TI - Magnetic measurements of the upper and lower critical fields of oxygen-deficient YBa2Cu3O7- delta single crystals. PMID- 9997125 TI - Full-penetration temperature and magnetic relaxation in a single crystal of Bi2Sr2CaCu2Ox. PMID- 9997126 TI - Quasiparticle tunneling and quasiparticle-pair interference in granular superconductors. PMID- 9997127 TI - Optical phonons in T*-structure Nd2-x-yCexSryCuO4. PMID- 9997128 TI - Structural changes of Bi1.8Sr2(Ca1-xYx)Cu2.2Oz ceramics with yttrium content studied by electron diffraction and high-resolution electron microscopy. PMID- 9997130 TI - Plasmon modes in a system composed of Cu-O layers and chains. PMID- 9997129 TI - Low-temperature specific heat of polycrystalline YBa2Cu3O6.70 in applied magnetic fields of 0, 1, 2, and 3 T. PMID- 9997131 TI - Zone-center (q=0) optical phonons in CuO studied by Raman and infrared spectroscopy. PMID- 9997132 TI - Variation of Tc and transport properties with carrier concentration in Y- and Pb doped Bi-based superconductors. PMID- 9997133 TI - Phase diagrams of oxygen ordering in high-temperature superconductors RBa2Cu3O7 x. PMID- 9997135 TI - Theory of the magnetoresistance in magnetic multilayers: Analytical expressions from a semiclassical approach. PMID- 9997134 TI - Magnetic and transport properties of BaV1-xTixS3 (0 <= x <= 0.2). PMID- 9997136 TI - Competing interactions in the heavy-electron antiferromagnets CeM2Sn2 (M=Ni, Ir, Cu, Rh, Pd, and Pt). PMID- 9997138 TI - Specific heat in some gadolinium compounds. II. Theoretical model. PMID- 9997137 TI - Specific heat in some gadolinium compounds. I. Experimental. PMID- 9997139 TI - Magnetism of Fe/Pd superlattices. PMID- 9997140 TI - Magnetic and electrical-resistance behavior of the compounds RPt2Ge2 (R=rare earth). PMID- 9997141 TI - Magnetic coupling through Cr: Study of spin polarization in Cr and film-growth effects. PMID- 9997142 TI - Long-range order near the Cu3Au(001) surface by evanescent x-ray scattering. PMID- 9997143 TI - Effect of an interchain magnetic interaction on the dimerized state of a two-XY quantum-spin-chain ladder. PMID- 9997144 TI - Elastic effects of an ac-driven charge-density wave in TaS3. PMID- 9997145 TI - Concept of a multimetrical space group. PMID- 9997146 TI - Crystal structure of and low-temperature phase transitions in isostructural RbSm(SO4)2 PMID- 9997147 TI - NMR and magnetization studies of Co/Cu superlattices. PMID- 9997148 TI - Magnetic structure of UNi2Si2. PMID- 9997150 TI - Moments of the Raman spectrum of the two-dimensional Heisenberg antiferromagnet. PMID- 9997149 TI - Spectral structure for a class of one-dimensional three-tile quasilattices. PMID- 9997151 TI - Dephasing by a dynamic asymmetric environment. PMID- 9997152 TI - Domain growth with time-dependent front velocity in one dimension. PMID- 9997153 TI - Influence of nonlinear dissipation on quantum tunneling. PMID- 9997154 TI - Electronic structure and magnetism of SrFeO3 and SrCoO3. PMID- 9997155 TI - Si29 magic-angle-spinning NMR spectroscopy of the ferroelastic-to-incommensurate transition in Sr2SiO4. PMID- 9997156 TI - Calculation of elastic constants from a replica Monte Carlo simulation. PMID- 9997157 TI - Low-temperature properties of a two-level system interacting with conduction electrons: An application of the overcompensated multichannel Kondo model. PMID- 9997158 TI - Pressure dependence of the melting temperature of solids: Rare-gas solids. PMID- 9997159 TI - Exchange interactions at the surface of a ferromagnet. PMID- 9997160 TI - Anomalous optical transmission in homogeneous latex suspensions. PMID- 9997161 TI - Anisotropic magnetic behavior in Dy/Y films and superlattices. PMID- 9997163 TI - Critical behavior of a system with orientational and positional degrees of freedom: A Monte Carlo simulation study. PMID- 9997162 TI - Observation of the Haldane gap in RbNiCl3. PMID- 9997164 TI - Crossover from a fractal lattice to a Euclidean lattice for the thermodynamic properties of a triplet-interaction Ising model. PMID- 9997165 TI - Instability of the Nagaoka ferromagnetic state in the Hubbard model with next nearest-neighbor hopping. PMID- 9997166 TI - Cluster-variation approach to the spin-1/2 XXZ model. PMID- 9997167 TI - Electronic and magnetic features of twisted spin-density-wave states in the two dimensional Hubbard model. PMID- 9997168 TI - S=1 antiferromagnetic Heisenberg chain in a magnetic field. PMID- 9997169 TI - Image states at ferromagnetic surfaces: Fe(110), (100), (111) and Co(0001). PMID- 9997170 TI - Strong magnetic x-ray dichroism in 2p absorption spectra of 3d transition-metal ions. PMID- 9997171 TI - Resonant-light absorption and the problem of observing the Kosterlitz-Thouless transition in spin-polarized atomic hydrogen adsorbed on a liquid-He surface. PMID- 9997172 TI - Real-time small-angle x-ray scattering study of the early stage of phase separation in the SiO2-BaO-K2O system. PMID- 9997173 TI - Dynamics of phonons in submicrometer zones generated by an optical waveguide. PMID- 9997174 TI - Anisotropic magnetoresistance of the semimetallic antiferromagnet EuAs3. PMID- 9997175 TI - Dynamics of a two-dimensional Heisenberg antiferromagnet at zero temperature. PMID- 9997177 TI - Localized-versus-extended spin fluctuations in quantum antiferromagnets. PMID- 9997176 TI - Self-dual model for one-dimensional incommensurate crystals including next nearest-neighbor hopping, and its relation to the Hofstadter model. PMID- 9997178 TI - Magnetic line groups. III. Corepresentations of the magnetic line groups isogonal to the point groups Dn, Cnv, Dnd, and Dnh. PMID- 9997179 TI - Long-range angular correlations of waves in a tube geometry. PMID- 9997180 TI - Two-dimensional axial third-nearest-neighbor Ising model and the S=1/2 anisotropic Heisenberg chain. PMID- 9997181 TI - Hubbard model: Functional-integral approach and diagrammatic perturbation theory. PMID- 9997182 TI - Theoretical isothermal equation of state of the high-pressure phases of silicon. PMID- 9997183 TI - Charge-carrier-trapping kinetics in a chain with chaotically distributed traps and broken bonds: Biased-random-walk model. PMID- 9997184 TI - Silver-ion disorder in alpha -AgI: A computer simulation study. PMID- 9997185 TI - Extension of the PMID- 9997186 TI - Critical properties of a one-dimensional frustrated quantum magnetic model. PMID- 9997187 TI - Critical properties of the quantum sine-Gordon equation. PMID- 9997188 TI - High-energy x-ray anomalous scattering factor for silicon: Reanalyses of the experimental data. PMID- 9997189 TI - Electron-spin-resonance studies of Cr-ion pairs in LiNbO3:Cr3+ PMID- 9997190 TI - Temporal fluctuations in disordered static optical media. PMID- 9997191 TI - Hyperuniversality in quantum critical phenomena. PMID- 9997192 TI - Condensate fraction and momentum distribution in the ground state of liquid 4He. PMID- 9997193 TI - Electronic structure of the organic superconductor kappa -(BEDT-TTF)2Cu(NCS)2 PMID- 9997194 TI - Microwave absorption across Tc: Determination of the angular dependence Hc2( theta )/Hc2. PMID- 9997195 TI - Evidence for collective pinning in high-temperature superconductors. PMID- 9997196 TI - Motion of a single hole in a resonating-valence-bond background: Some exact results. PMID- 9997198 TI - Bulk phase transition in YBa2Cu3O7- delta single crystals. PMID- 9997197 TI - In-plane transport properties of single-crystal R2-xCexCuO4-y (R=Nd,Sm). PMID- 9997200 TI - Finite-size study of the excitation and thermodynamics of the two-dimensional spin-1/2 Heisenberg antiferromagnet: Comparison with spin-wave theory. PMID- 9997199 TI - Monte Carlo simulation of reorientation driven by oxygen transport in YBa2Cu3O6.5. PMID- 9997201 TI - High-temperature superconductivity in a Y-Ba-Cu-based system without extraneous oxygen. PMID- 9997202 TI - Role of non-symmetry-breaking order parameters in determining the martensitic energy barrier: The bcc-to-9R transformation. PMID- 9997204 TI - Zero-temperature entropy of a replica-symmetric spin glass. PMID- 9997203 TI - Interacting-fermion approximation in the two-dimensional axial next-nearest neighbor Ising model. PMID- 9997206 TI - Phase diagram of the transverse Ising model in a random field. PMID- 9997205 TI - Dynamic mean-field approximation for the random-bond Ising-spin model. PMID- 9997209 TI - Continued-fraction formalism applied to the spin-1/2 XYZ model. PMID- 9997208 TI - Anomalously slow domain growth due to a modulus inhomogeneity in phase-separating alloys. PMID- 9997207 TI - Local spin correlations in ultrathin Fe/W(100) films. PMID- 9997210 TI - Effect of thermal spin-wave fluctuations on optical guided waves propagating in a magnetic film. PMID- 9997211 TI - Finite-size effects on the optical conductivity of a half-filled Hubbard ring. PMID- 9997212 TI - Mean-field Green's-function theory of the two-sublattice Ising model in a transverse field. PMID- 9997213 TI - Antiferromagnetic Heisenberg model with anisotropic coupling between nearest and next-nearest neighbors. PMID- 9997214 TI - Orbital band magnetism in actinide intermetallics. PMID- 9997215 TI - Specific-heat relaxation in glycerol. PMID- 9997216 TI - Comment on "Uniaxial anisotropic flux trapping in Y-Ba-Cu-O and Bi-Sr-Ca-Cu-O single crystals" PMID- 9997218 TI - Comment on "Nonlinear susceptibilities of granular matter" PMID- 9997217 TI - Reply to "Comment on 'Uniaxial anisotropic flux trapping in Y-Ba-Cu-O and Bi-Sr Ca-Cu-O single crystals' " PMID- 9997219 TI - Erratum: Dilute spin glass at zero temperature in general dimension PMID- 9997220 TI - Erratum: Entropy transport in high-Tc superconductors in the fluctuation regime PMID- 9997221 TI - Erratum: Surface electronic structure of Ce in the alpha and gamma phase PMID- 9997222 TI - Spin-wave expansion of the staggered magnetization of a square-lattice Heisenberg antiferromagnet at T=0. PMID- 9997223 TI - Nonlinear backscattering from opaque media. PMID- 9997224 TI - Experimental and molecular-dynamics study of the Ar emission mechanism during low energy Ar+ bombardment of Cu. PMID- 9997225 TI - Effect of random noise on a mode-locked system. PMID- 9997226 TI - Radio-frequency spectral response of two-dimensional Josephson-junction arrays. PMID- 9997227 TI - Evidence for surface barriers and their effect on irreversibility and lower critical-field measurements in Y-Ba-Cu-O crystals. PMID- 9997228 TI - Comparison of p and He channeling across Tc in YBa2Cu3O7-x. PMID- 9997229 TI - Pressure dependence of the superconducting phases in UPt3. PMID- 9997230 TI - Direct imaging of the oxygen sublattice in YBa2Cu3O7- delta superconductors by high-resolution electron microscopy. PMID- 9997231 TI - Critical fields and Landau-Ginzburg parameters of the heavy-fermion superconductor UPt3. PMID- 9997232 TI - Phase separation, charge-transfer instability, and superconductivity in the three band extended Hubbard model: Weak-coupling theory. PMID- 9997233 TI - Unconventional electron-phonon interactions in high-temperature superconductors. PMID- 9997234 TI - Scaling of the hysteretic magnetic behavior in YBa2Cu3O7 single crystals. PMID- 9997235 TI - Correlated random-phase-approximation study of an anyon gas. PMID- 9997236 TI - Seebeck effect in the mixed state of epitaxial YBa2Cu3O7. PMID- 9997237 TI - Lower bounds for the ground-state energies of the two-dimensional Hubbard and t-J models. PMID- 9997238 TI - Real-space renormalization-group study of random-superconductor models. PMID- 9997239 TI - Temperature dependence of the linewidths of the Raman-active phonons of YBa2Cu3O7: Evidence for a superconducting gap between 440 and 500 cm-1. PMID- 9997240 TI - Critical surface of the Blume-Emery-Griffiths model on the honeycomb lattice. PMID- 9997241 TI - Feasibility of fast-particle channeling in quasicrystals. PMID- 9997242 TI - Period and amplitude halving in mesoscopic rings with spin. PMID- 9997243 TI - Lattice instability and low-temperature phase transition in Pr2NiO4. PMID- 9997244 TI - Variational wave functions and the Mott transition. PMID- 9997245 TI - In-phase flux state of the two-dimensional antiferromagnetic Heisenberg model and the Raman spectrum of La2CuO4. PMID- 9997246 TI - Local electronic properties of one-dimensional quasiperiodic systems. PMID- 9997247 TI - Many-body correlations in quantum antiferromagnets: A microscopic coupled-cluster approach. PMID- 9997248 TI - Chirality selection by magnetoelectric coupling in frustrated hexagonal antiferromagnets. PMID- 9997249 TI - Conduction-electron screening and surface properties of Cs metal. PMID- 9997250 TI - Optical properties of two-dimensional disordered systems on a substrate. PMID- 9997251 TI - Truncation-rod scattering: Analysis by the dynamical theory of x-ray diffraction. PMID- 9997252 TI - Accommodation of the lattice mismatch in a Ag/Ni heterophase boundary. PMID- 9997253 TI - Infrared properties of Pt/Al2O3 cermet films. PMID- 9997254 TI - Voltage drop in mesoscopic systems: A numerical study using a quantum kinetic equation. PMID- 9997255 TI - Resonances of small metal clusters excited in inelastic electron scattering. PMID- 9997256 TI - First-principles calculation of positron lifetimes in solids. PMID- 9997257 TI - Au(111): A theoretical study of the surface reconstruction and the surface electronic structure. PMID- 9997258 TI - Diffusion of interacting particles in metals based on the quantum-lattice-gas model. PMID- 9997260 TI - Phonons and librons in nitrogen monolayers adsorbed on graphite. PMID- 9997259 TI - Parametrization of the electronic structure of Z+1 impurities. PMID- 9997261 TI - Electronic-band-structure calculations and soliton dynamics for polyketene and related compounds. PMID- 9997263 TI - Nonlinear photocarrier drift in hydrogenated amorphous silicon-germanium alloys. PMID- 9997262 TI - Effects of growth temperature on atom distributions, Fermi-level positions, and valence-band offsets for Ge/n-type InP(110) heterojunctions. PMID- 9997264 TI - Stopping power for low-velocity Mg ions in Si, Ge, and GaAs. PMID- 9997266 TI - Dynamics of inter- and intra-growth-island exciton localization in GaAs single quantum wells. PMID- 9997265 TI - Vibrational assignments in the conductivity spectra of semiconducting (TMTSF)2ReO4 and (TMTSF)2BF4 (where TMTSF is tetramethyltetraselenafulvalene) for radiation polarized perpendicular to the chains. PMID- 9997267 TI - Far-infrared spectroscopy of minibands and confined donors in GaAs/AlxGa1-xAs superlattices. PMID- 9997268 TI - Optical studies of vertical ambipolar transport and interface recombination velocities in GaAs/Al0.5Ga0.5As double-quantum-well heterostructures. PMID- 9997269 TI - Pressure dependence of the photoluminescence of polyparaphenylene. PMID- 9997270 TI - Two-stream instabilities in solid-state plasmas caused by conventional and unconventional mechanisms. PMID- 9997271 TI - Electronic structure of the rocksalt-structure semiconductors ZnO and CdO. PMID- 9997272 TI - Optical-reflectance anisotropy in epitaxial metastable (GaAs)1-x(Si2)x(001) alloys: A probe for the zinc-blende-to-diamond structural transition. PMID- 9997273 TI - Shear-deformation-potential constant of the conduction-band minima of Si: Experimental determination by the deep-level capacitance transient method. PMID- 9997275 TI - Structural phase transition in (GaAs)1-xGe2x and (GaP)1-xSi2x alloys: Test of the bulk thermodynamic description. PMID- 9997274 TI - Subpicosecond kinetics of band-edge absorption in Al0.25Ga0.75As. PMID- 9997276 TI - Decay of the population of quasilocal states in disordered media. PMID- 9997277 TI - Nonlocal theory of collective excitations in quantum-dot arrays. PMID- 9997278 TI - Photoluminescence spectroscopy in GaAs/AlAs superlattices as a function of temperature and pressure: The influence of sample quality. PMID- 9997279 TI - Band-edge hole mass in strained-quantum-well structures. PMID- 9997280 TI - Scanning tunneling microscopy of Ag growth on GaAs(110) at 300 K: From clusters to crystallites. PMID- 9997281 TI - Optical absorption and Zeeman effect of Cu2+ in tetrahedrally coordinated crystals. PMID- 9997282 TI - Intraband and interband magneto-optics of p-type In0.18Ga0.82As/GaAs quantum wells. PMID- 9997284 TI - Quasiparticle band structure of thirteen semiconductors and insulators. PMID- 9997283 TI - Diffusion-to-streaming transition in a two-dimensional electron system in a polar semiconductor. PMID- 9997286 TI - Electromagnetic response of an electron gas in one-dimensional quantum wires. PMID- 9997285 TI - Adatom-induced donor states during the early stages of Schottky-barrier formation: Ga, In, and Pb on Si(113). PMID- 9997287 TI - Impurity photoconduction, excitons, and effective masses in liquid xenon. PMID- 9997288 TI - Screening of the Coulomb repulsion in transition-metal oxides and sulfides. PMID- 9997289 TI - Bands versus bonds in sulfides: Theoretical investigation of the luminescence of copper in zinc sulfide. PMID- 9997290 TI - Optical studies of the 1.40-eV Ni center in diamond. PMID- 9997292 TI - Solid solutions of alkali halide compounds. II. Physical properties and vacancy contributions. PMID- 9997291 TI - Solid solutions of alkali halide compounds. I. Configurational and vibrational contributions. PMID- 9997293 TI - Spin relaxation in GaAs-AlxGa1-xAs heterostructures in high magnetic fields. PMID- 9997294 TI - Effect of oxygen on the electronic properties of Pd. PMID- 9997295 TI - Lattice thermal conductivity of Na. PMID- 9997296 TI - Dynamical correlation effects in alkali metals. PMID- 9997297 TI - Coupled surface-plasmon-polariton waves and the optical size effect on the optical reflectance of metal-insulator superlattices. PMID- 9997298 TI - Size-dependent dielectric response of small metal particles. PMID- 9997299 TI - Cohesive energies of crystals. PMID- 9997300 TI - Quantum-confined excitonic states at high-quality interfaces in GaAs(n type)/AlxGa1-xAs(p type) double heterostructures. PMID- 9997301 TI - Long-range forces and the moments method. PMID- 9997302 TI - Microvoid formation in low-temperature molecular-beam-epitaxy-grown silicon. PMID- 9997303 TI - Conduction mechanisms in BaTiO3 thin films. PMID- 9997304 TI - Impurity optical absorption of HgGa2Se4:Co2+ single crystals. PMID- 9997305 TI - Absolute two-phonon Raman cross section in potassium chloride. PMID- 9997306 TI - Erratum: Disorder effects on the density of states of the II-VI semiconductor alloys Hg0.5Cd0.5Te, Cd0.5Zn0.5Te, and Hg0.5Zn0.5Te PMID- 9997307 TI - Erratum: Absolute deformation potentials in semiconductors PMID- 9997308 TI - Disappearance of the Coulomb charging energy and low-temperature resistivity of granular metals. PMID- 9997309 TI - alpha -gallium: A metallic molecular crystal. PMID- 9997310 TI - Local-density-functional calculation of photoelectron spectra of fullerenes. PMID- 9997311 TI - Excitons in InAs/GaAs submonolayer quantum wells. PMID- 9997312 TI - Magneto-optical transitions and level crossings in a Coulomb-coupled pair of quantum dots. PMID- 9997313 TI - Wigner solid from finite-cluster studies. PMID- 9997314 TI - Migration of the H2* complex and its relation to H- in n-type silicon. PMID- 9997315 TI - High-resolution synchrotron-radiation core-level spectroscopy of decapped GaAs(100) surfaces. PMID- 9997316 TI - Polarized vibrational density of states of polyacetylene from incoherent inelastic neutron scattering. PMID- 9997318 TI - Potassium-induced unrelaxation of the GaAs(110) surface. PMID- 9997317 TI - Spatial inhomogeneity and void-growth kinetics in the decomposition of ultrathin oxide overlayers on Si(100). PMID- 9997319 TI - Antimony-induced electronic states in the Sb/InP(110) interface studied by high resolution electron-energy-loss spectroscopy. PMID- 9997320 TI - Subband effect on ballistic resistance in a side-gated narrow wire junction. PMID- 9997321 TI - Interband absorption spectra and Sommerfeld factors of a one-dimensional electron hole system. PMID- 9997323 TI - Anomalous Rxx in the quantum Hall regime due to impurity-bound states. PMID- 9997322 TI - Absorption-spectral-shape analysis of the band-edge exciton in a BiI3 crystal based on the exciton-phonon interaction. PMID- 9997324 TI - Reconstruction of the (100) surfaces of Au and Ag. PMID- 9997325 TI - Sticking coefficient of light particles on surfaces. PMID- 9997326 TI - Local electronic structure of magnetic fcc palladium. PMID- 9997328 TI - Aharonov-Bohm flux and statistics of energy levels in metals. PMID- 9997327 TI - Adsorbate-induced surface core-level shifts of Pd(110). PMID- 9997329 TI - Formation of secondary cluster ions during sputtering of silver and copper. PMID- 9997331 TI - Dependence of the electronic structure on local atomic order in ternary Cu2NiZn alloys. PMID- 9997330 TI - Band structure and cohesive properties of 3d-transition-metal carbides and nitrides with the NaCl-type structure. PMID- 9997332 TI - Spin-polarized relativistic linear-muffin-tin-orbital method: Volume-dependent electronic structure and magnetic moment of plutonium. PMID- 9997333 TI - Scattered-wave integral-transform method of holographic-image reconstruction from forward-scattering diffraction patterns. PMID- 9997334 TI - Calculation of spin- and angle-resolved photoemission spectra from Pd(100) coated with a monolayer of a magnetic 3d metal, Cr or Mn: Comparison between antiferromagnetic and ferromagnetic configurations. PMID- 9997335 TI - Effect of vacuum annealings on the electronic properties of clean Si(111) surfaces. PMID- 9997337 TI - Vibrational properties and infrared spectra of AlxGa1-xAs systems. II. Order and disorder features in superlattice configuration. PMID- 9997336 TI - Vibrational properties and infrared spectra of AlxGa1-xAs systems. I. Average-t matrix approximation versus supercell calculation for homogeneous alloys. PMID- 9997338 TI - Diffusion and solubility of copper, silver, and gold in germanium. PMID- 9997339 TI - Probing of pi conjugation in trans-polyacetylene using near-infrared photoluminescence spectroscopy. PMID- 9997340 TI - Surface effects in hydrogenated amorphous silicon studied by photothermal deflection experiments. PMID- 9997341 TI - Role of the hydrogen atom on metastable defects in GaAs. PMID- 9997343 TI - Macroscopic theory of optical phonons in superlattices. PMID- 9997342 TI - Exciton binding energy and subband structures of GaAs/AlxGa1-xAs superlattices. PMID- 9997344 TI - Positron annihilation in a single crystal of CoSi2: Experiment and theory. PMID- 9997346 TI - Interatomic force fields for the structure of intrinsic point defects in silicon. PMID- 9997345 TI - Optically detected magnetic resonance of group-IV and group-VI impurities in AlAs and AlxGa1-xAs with x >= 0.35. PMID- 9997347 TI - Resonant spin-flip Raman scattering on photoexcited carriers in p-type Cd0.95Mn0.05Te crystals. PMID- 9997348 TI - Kinetics of holes optically excited from the AsGa EL2 midgap level in semi insulating GaAs. PMID- 9997349 TI - Absorption and photoluminescence of ultrathin pseudomorphic InAs/GaAs quantum wells. PMID- 9997350 TI - Ultraviolet-photoemission-spectroscopy study of the interaction of atomic hydrogen with cleaved InP: A valence-band contribution. PMID- 9997351 TI - Angle-resolved photoemission studies of the CdTe(110) surface. PMID- 9997352 TI - Electronic and optical properties of strained Ge/Si superlattices. PMID- 9997353 TI - Photomodulated transmission spectroscopy of the intersubband transitions in strained In1-xGaxAs/GaAs multiple quantum wells under hydrostatic pressure. PMID- 9997354 TI - Phenomenological investigations of S(k, omega ) of the two-dimensional electron gas in the memory-function formalism. PMID- 9997355 TI - Optical investigation of a strain-induced mixed type-I-type-II superlattice system: CdTe/Cd1-xZnxTe. PMID- 9997356 TI - Two-dimensional warm-electron transport in GaAs and In1-xGaxAs quantum wells at low temperatures. PMID- 9997357 TI - Mechanism of low-temperature ( <= 300 degreesC) crystallization and amorphization for the amorphous Si layer on the crystalline Si substrate by high-energy heavy ion beam irradiation. PMID- 9997358 TI - Coupled plasmon-phonon excitations in quasi-one-dimensional quantum-well wires. PMID- 9997359 TI - Electronic structures of NiO, CoO, and FeO studied by 2p core-level x-ray photoelectron spectroscopy. PMID- 9997360 TI - Measurement of the piezoelectric tensor of an organic crystal by the x-ray method: The nonlinear optical crystal 2-methyl 4-nitroaniline. PMID- 9997361 TI - Interaction of an inserted monolayer well with the conduction band of a Si/Si1 xGex superlattice. PMID- 9997362 TI - Image potential matched self-consistently to an effective potential for simple metal surfaces. PMID- 9997363 TI - Microscopic study of the phonon dispersion in Tb. PMID- 9997364 TI - Quantum tunneling and relaxation in asymmetric coupled wells. PMID- 9997366 TI - Electrical conduction in the Si(111):B-( sqrt 3 x sqrt 3 )R30 degrees/a-Si interface reconstruction. PMID- 9997365 TI - Magnetoexcitons in narrow GaAs/Ga1-xAlxAs quantum wells. PMID- 9997367 TI - Comment on "Temperature-induced intraband transitions in the n-type HgTe/CdTe superlattice" PMID- 9997368 TI - Metallic behavior stable against Peierls instability in the one-dimensional organic conductor tetraselenotetracene-bis(1,2,5 thiadiazolo)tetracyanoquinodimethane PMID- 9997369 TI - Electronic structure of a single layer of Na on Cu(111). PMID- 9997370 TI - Theory of vacancy-stabilized ( sqrt 3 x sqrt 3 ) displacive reconstruction of the clean Si(111) surface. PMID- 9997371 TI - Observation of the double-step-single-step transition on a vicinal surface of Si(100). PMID- 9997372 TI - Determination of the hole effective masses in GaAs from acceptor spectra. PMID- 9997373 TI - Fermi-edge singularities and enhanced magnetoexcitons in the optical spectra of GaAs/(Ga,Al)As single quantum wells. PMID- 9997374 TI - Interference between electronic and LO-vibronic inelastic light scattering in periodically delta -doped GaAs. PMID- 9997375 TI - Excited states of one-dimensional excitons in polysilanes as investigated by two photon spectroscopy. PMID- 9997376 TI - Boundary-related scattering processes in quasiballistic narrow wires. PMID- 9997378 TI - Unoccupied energy bands, exchange splitting, and self-energy of iron. PMID- 9997377 TI - Infrared reflectivity by transverse-optical phonons in (GaAs)m/(AlAs)n ultrathin layer superlattices. PMID- 9997379 TI - Magnetic-field dependence of the hole-hole interaction in fluorine-intercalated graphite fibers. PMID- 9997381 TI - Theory of metallic clusters: Asymptotic size dependence of electronic properties. PMID- 9997380 TI - Collective excitations in open-shell metal clusters: The time-dependent local density approximation applied to the self-consistent spheroidal jellium particle. PMID- 9997382 TI - Electron spectroscopy in the URh3Bx system. PMID- 9997383 TI - Multiphonon absorption of light in nonpolar crystals. PMID- 9997384 TI - Vibrational line shapes at surfaces. PMID- 9997385 TI - Requirements for structure determination of aperiodic crystals. PMID- 9997386 TI - Electronic properties of two-dimensional quasicrystals with near-neighbor interactions. PMID- 9997387 TI - Weak localization, electron-electron interactions, and Joule heating in the presence of a microwave electric field in thin metal films. PMID- 9997388 TI - LIII-edge spectroscopy on cerium-based intermediate-valent compounds. PMID- 9997389 TI - Self-consistent implementation of nonlocal exchange and correlation in a Gaussian density-functional method. PMID- 9997390 TI - Potassium-induced reconstruction of Ag(001). PMID- 9997391 TI - Energetics and electronic structures of hydrogenated metal clusters. PMID- 9997393 TI - Degradation and regeneration of copper electrical junctions. PMID- 9997392 TI - Fine-line interactions in Al/Hf/Al thin films. PMID- 9997394 TI - H-point phonon in molybdenum: Superlinearized augmented-plane-wave calculations. PMID- 9997395 TI - Charge transfer in transition-metal alloying: Charge-tailing effects. PMID- 9997396 TI - Local-density approximation: Cohesion in the transition metals and s-->d promotion in the transition-metal atoms. PMID- 9997397 TI - Theory of hopping rate of localized charged particles in metals: Electron scattering. PMID- 9997398 TI - Coulombic and neutral trapping centers in silicon dioxide. PMID- 9997399 TI - Structure of B13C2. PMID- 9997400 TI - Critical test of CdTe(100) angle-resolved photoemission spectra with band structure calculations. PMID- 9997401 TI - Exciton Green's-function approach to optical absorption in a quantum well with an applied electric field. PMID- 9997402 TI - Microwave thermal modulation of photoluminescence in III-V semiconductors. PMID- 9997403 TI - Detailed surface and gas-phase chemical kinetics of diamond deposition. PMID- 9997404 TI - Exciton localization in InxGa1-xAs/GaAs quantum wells observed by temperature modulated photoluminescence. PMID- 9997405 TI - Doubly resonant Raman scattering in the semimagnetic semiconductor Cd0.95Mn0.05Te. PMID- 9997406 TI - Boron-hydrogen complexes in crystalline silicon. PMID- 9997407 TI - Elastic scattering of electrons by neutral donor impurities in silicon. PMID- 9997408 TI - Thermodynamic instability of ordered (001) AlGaAs2 in bulk form. PMID- 9997409 TI - Predicting structural energies of atomic lattices. PMID- 9997410 TI - Confined LO phonons in GaAs/AlAs superlattices. PMID- 9997412 TI - Photoemission and low-energy-electron-diffraction study of clean and oxygen-dosed Cu2O (111) and (100) surfaces. PMID- 9997411 TI - Free-to-bound and light- and heavy-hole bound-exciton transitions in AlxGa1-xAs GaAs multiple quantum wells. PMID- 9997414 TI - Hydrogen dynamics in a-Si:H: Multiple trapping, structural relaxation, and the Meyer-Neldel relation. PMID- 9997413 TI - Static correlations in superlattices. PMID- 9997415 TI - Perturbation theory of the electronic properties in strongly correlated solids. PMID- 9997416 TI - Inelastic-electron-scattering cross sections for Si, Cu, Ag, Au, Ti, Fe, and Pd. PMID- 9997417 TI - Disorder effects on the density of states of the II-VI semiconductor alloys Hg0.5Cd0.5Te, Cd0.5Zn0.5Te, and Hg0.5Zn0.5Te. PMID- 9997418 TI - Acetylene reaction with the Si(111) surface: A semiempirical quantum chemical study. PMID- 9997419 TI - Vibrational properties of Si/Ge superlattices incorporating biatomic sheets of silicon and germanium. PMID- 9997420 TI - Electronic structures of GdAs/GaAs superlattices. PMID- 9997421 TI - Analysis of guided electron waves in coupled quantum wells. PMID- 9997422 TI - Magneto-optical absorption by electrons in the presence of parabolic confinement potentials. PMID- 9997423 TI - Femtosecond excitonic bleaching recovery in the optical Stark effect of GaAs/AlxGa1-xAs multiple quantum wells and directional couplers. PMID- 9997424 TI - Integral-equation approach to medium-range order in molten and glassy chalcogenides. PMID- 9997425 TI - Nonlinear charge-density-wave dynamics in inhomogeneous conditions. PMID- 9997426 TI - Phase-sensitive optical detection of ballistic phonon heat pulses using frequency modulation spectroscopy and persistent spectral holes. PMID- 9997427 TI - Light scattering in superionic glasses (AgI)x(AgPO3)1-x: Brillouin and Raman scattering. PMID- 9997429 TI - Resonant Raman effect and Fano distortion in the stage-2 graphite donor intercalation compound C/Rb. PMID- 9997428 TI - X-ray-absorption near-edge structure of alkali halides: The interatomic-distance correlation. PMID- 9997431 TI - Precipitation of Ba2+ ions in KCl using Eu2+ as an optical probe. PMID- 9997430 TI - Time-resolved spectroscopy of the luminescence in KBr:Sn2+ crystals. PMID- 9997432 TI - Optical properties of color centers in calcium-stabilized gadolinium gallium garnets. PMID- 9997434 TI - Lattice dynamics of fct indium and hcp magnesium. PMID- 9997433 TI - Theory of high-pressure phases of Pb. PMID- 9997435 TI - Added-row growth of the (2 x 1)O-Cu(110) reconstruction. PMID- 9997436 TI - First-principles calculation of the elastic moduli of Ni3Al. PMID- 9997437 TI - Vacancy-vacancy interaction in silicon studied using atomic potentials. PMID- 9997438 TI - Reduced differential current: A conserved quantity in short-scale transport. PMID- 9997439 TI - Two reaction channels directly observed for atomic hydrogen on the Si(111)-7 x 7 surface. PMID- 9997440 TI - Tetracoordinated quasicrystals. PMID- 9997441 TI - Binding energies and density of impurity states of shallow hydrogenic impurities in cylindrical quantum-well wires. PMID- 9997442 TI - Comment on "Dynamical aspects of luminescence from GaAs-AlAs single quantum wells under hydrostatic pressure" PMID- 9997444 TI - Electronic structure of (1 x 1) H/Mo(001): Two-dimensional Fermi. PMID- 9997443 TI - Erratum: Interface-response theory of electromagnetism in dielectric superlattices PMID- 9997445 TI - Inductive anomaly and noise spectrum of a sliding-charge-density-wave conductor. PMID- 9997447 TI - Surface kinetics and roughness on microstructure formation in thin films. PMID- 9997446 TI - Hole-tunneling dynamics in biased GaAs/Al0.35Ga0.65As asymmetric double quantum wells. PMID- 9997448 TI - Adsorption of phosphorus on Si(111): Structure and chemical reactivity. PMID- 9997449 TI - Lowest-order vertex corrections to the energy gap in covalent semiconductors. PMID- 9997450 TI - Tunneling through highly transparent symmetric double barriers. PMID- 9997451 TI - Molecular-dynamics simulations of the stability of amorphous silicon. PMID- 9997452 TI - Structural effects on the calculated semiconductor gap of CrSi2. PMID- 9997453 TI - Resonant tunneling between heavy-hole and light-hole states in coupled quantum wells. PMID- 9997455 TI - Crystalline metastable phase in pressure-cycled epitaxial GaAs. PMID- 9997454 TI - Direct coupling of heavy-hole free excitons in InxGa1-xAs/GaAs quantum wells with free excitons in the GaAs barrier. PMID- 9997456 TI - Theory of multiharmonic generation and multiphoton electron emission at a metal surface. PMID- 9997457 TI - Charge-density-wave instabilities expected in monophosphate tungsten bronzes. PMID- 9997458 TI - Far-infrared reflection-absorption spectroscopy of ultrathin films. PMID- 9997460 TI - Renormalized theory of sticking and desorption for physisorption. PMID- 9997459 TI - Islandlike in-plane structure and vibrational behavior of NiCl2 intercalated in graphite. PMID- 9997461 TI - Transmission (e,2e) coincidence measurements of thin evaporated carbon, graphite, and aluminum-aluminum oxide foils. PMID- 9997462 TI - Crystal structure, phase stability, and electronic structure of Ti-Al intermetallics: Ti3Al. PMID- 9997463 TI - Calculation of the optical spectra of beta '-NiAl and CoAl. PMID- 9997464 TI - Calculation of spin- and angle-resolved photoemission spectra from Pd(100) coated with a monolayer of a magnetic 3d metal: Fe, Co, and Ni. PMID- 9997465 TI - Molecular adsorption on oxide surfaces: Electronic structure and orientation of NO on NiO(100)/Ni(100) and on NiO(100) as determined from electron spectroscopies and ab initio cluster calculations. PMID- 9997467 TI - Efficient pseudopotentials for plane-wave calculations. PMID- 9997466 TI - X-ray-absorption studies of krypton precipitates in solid matrices. PMID- 9997468 TI - Displacement distributions in diffusion by atomic replacement: Ir atoms on Ir surfaces. PMID- 9997469 TI - Twin-boundary and stacking-fault energies in Al and Pd. PMID- 9997470 TI - Image-potential states on Ni(111) measured by inverse-photoemission spectroscopy. PMID- 9997472 TI - Phonons in a strongly coupled electron-phonon system. PMID- 9997471 TI - Magnetoplasmon polaritons in finite n-i-p-i superlattices. PMID- 9997473 TI - Electronic structure of strained-layer AlAs/InAs (001) superlattices. PMID- 9997475 TI - Excitons in anisotropic solids: The model of fractional-dimensional space. PMID- 9997474 TI - Prediction of the effect of the sample biasing in scanning tunneling microscopy and of surface defects on the observed character of the dimers in the Si(001)-(2 x 1) surface. PMID- 9997476 TI - Pressure-induced negative charge state of the EL2 defect in its metastable configuration. PMID- 9997477 TI - Raman scattering by coupled intersubband-Landau-level excitations in quantum-well structures. PMID- 9997478 TI - Vibrational properties of CdGeP2. PMID- 9997479 TI - Dynamic properties of double-barrier resonant-tunneling structures. PMID- 9997481 TI - Plasma losses by charged particles in thin films: Effects of spatial dispersion, phonons, and magnetic field. PMID- 9997480 TI - Dielectric response and quantum magnetic-field effects on the screening properties of a slab of solid-state plasma. PMID- 9997483 TI - Local-field effects on the reflectance anisotropy of Si(110):H. PMID- 9997482 TI - pi bands and gap states from optical absorption and electron-spin-resonance studies on amorphous carbon and amorphous hydrogenated carbon films. PMID- 9997484 TI - Optical detection of electron-nuclear double resonance for an S=1 luminescent center in GaP:O. PMID- 9997486 TI - Temperature-dependent angle-resolved photoemission study of the linewidth of surface states of III-V semiconductors. PMID- 9997485 TI - Elastic properties of amorphous Si and derived Debye temperatures and Gruneisen parameters: Model calculation. PMID- 9997487 TI - Coupled tunneling plasmon excitations in a planar array of quantum dots. PMID- 9997488 TI - Static local-field corrections of two-dimensional electron liquids. PMID- 9997489 TI - Highly conducting polyacetylene: Three-dimensional delocalization. PMID- 9997490 TI - Quasiballistic electronic transport in a tunneling hot-electron-transfer amplifier. PMID- 9997491 TI - Effects of lattice relaxation on deep levels in semiconductors. PMID- 9997492 TI - Magnetic-field-induced resonant tunneling across a thick square barrier. PMID- 9997493 TI - Pseudopotential plane-wave calculations for ZnS. PMID- 9997494 TI - Piezomodulation spectroscopy: A powerful investigation tool of heterostructures. PMID- 9997496 TI - Quantum confinement effects at the L point in CdTe. PMID- 9997495 TI - Picosecond two-beam coupling and polarization rotation by scalar gratings in undoped cadmium telluride at 1.064 microm. PMID- 9997497 TI - Optical studies on InP:Fe by Fourier-transform emission and absorption spectroscopy. PMID- 9997498 TI - Miniband structure in InxGa1-xAs-GaAs strained-layer superlattices. PMID- 9997500 TI - Optical study of the electronic states of In0.53Ga0.47As/In0.52Al0.48As quantum wells in high electric fields. PMID- 9997499 TI - Classification of spontaneous oscillations at the onset of avalanche breakdown in p-type germanium. PMID- 9997501 TI - Nonlinear dielectric response to a point-donor impurity of an electron-gas-model semiconductor that includes the effect of the Dirac-Slater exchange correlation. PMID- 9997503 TI - Matrix method of solution of the Boltzmann equation for hot-acceptor photoluminescence. PMID- 9997502 TI - Resonant tunneling of holes in Si/SixGe1-x quantum-well structures. PMID- 9997504 TI - Divacancy acceptor levels in ion-irradiated silicon. PMID- 9997505 TI - Raman microprobe scattering of solid silicon and germanium at the melting temperature. PMID- 9997506 TI - Electronic structure of superlattices incorporating diluted magnetic semiconductors. PMID- 9997508 TI - Harmonic oscillator on a lattice in a constant force field and associated Bloch oscillations. PMID- 9997507 TI - Structure of germanium-selenium glasses: An x-ray-absorption fine-structure study. PMID- 9997509 TI - Even-parity excited states of Ag-centers in alkali halides. PMID- 9997510 TI - Intrinsic localized modes in a monatomic lattice with weakly anharmonic nearest neighbor force constants. PMID- 9997511 TI - Anisotropic cross sections in low-energy electron-reflection spectroscopy on solids. PMID- 9997512 TI - Raman spectroscopic study of the pressure-induced coordination change in GeO2 glass. PMID- 9997514 TI - Rayleigh mode in amorphous hydrogenated carbon films. PMID- 9997513 TI - First-principles calculations of defect-induced lattice relaxation in ionic systems. PMID- 9997515 TI - Characterization of an intermediate-case exciton in the 580-nm emission of Cd doped and pure AgBr. PMID- 9997516 TI - Nature of the temperature dependence of conduction bands in polyethylene. PMID- 9997517 TI - Inelastic neutron- and Raman-scattering studies of muscovite and vermiculite layered silicates. PMID- 9997519 TI - Effect of hydrostatic pressure on the Fermi surface of Pd and Pt. PMID- 9997518 TI - Surface strain of tungsten (001). PMID- 9997520 TI - van der Waals interactions between sharp probes and flat sample surfaces. PMID- 9997521 TI - Effect of ambipolar diffusion on the hot-carrier relaxation in semiconductors. PMID- 9997522 TI - Low-temperature lattice-scattering mobility in multiple heterojunctions: Phonon drag enhancement. PMID- 9997523 TI - Magnetic susceptibility of InP, InAs, and InSb. PMID- 9997524 TI - Conservation of bond lengths in strained Ge-Si layers. PMID- 9997526 TI - Reply to "Comment on 'Existence of Wannier-Stark localization" PMID- 9997525 TI - Comment on "Existence of Wannier-Stark localization" PMID- 9997527 TI - Faraday spectroscopy in diluted-magnetic-semiconductor superlattices. PMID- 9997528 TI - Variable-range-hopping magnetoresistance. PMID- 9997529 TI - Biexcitonic contribution to the degenerate-four-wave-mixing signal from a GaAs/AlxGa1-xAs quantum well. PMID- 9997530 TI - Inelastic-scattering effects on single-barrier tunneling. PMID- 9997531 TI - H passivation of Si impurities in GaAs. PMID- 9997532 TI - Tuning AlAs-GaAs band discontinuities and the role of Si-induced local interface dipoles. PMID- 9997533 TI - Hydrogen chemical potential and structure of a-Si:H. PMID- 9997534 TI - Gallium interstitials in GaAs/AlAs superlattices. PMID- 9997535 TI - Substitutionality of Te- and Sn-related DX centers in AlxGa1-xAs. PMID- 9997536 TI - Further aspects of enhanced ion scattering near 180 degrees. PMID- 9997537 TI - Finite Debye-Waller factor for "classical" atom-surface scattering. PMID- 9997538 TI - Molecular dynamics of collision cascades with composite pair-many-body potentials. PMID- 9997539 TI - Heavy-ion-induced electron emission from thin carbon foils. PMID- 9997540 TI - Dynamic approach to local-polarization distribution and NMR line shape in deuteron glasses. PMID- 9997542 TI - Spin-memory effect of Tm2+ in cubic fields. PMID- 9997541 TI - Tl2+ EPR study of the dynamics of the proton-glass transition in Rb1 x(NH4)xH2PO4. PMID- 9997543 TI - Electron-spin resonance of stable radicals in Langmuir-Blodgett films of a merocyanine dye: Study of hyperfine coupling using a 15N-enriched dye. PMID- 9997544 TI - Derivation of a master equation for charge-transfer processes in atom-surface collisions. PMID- 9997545 TI - Applicability of the kinematic pair-density-matrix theory to optically detected magnetic-resonance spectra of two-dimensional molecular crystals. PMID- 9997546 TI - Neutron-scattering study of the magnon energies and intensities in iron. PMID- 9997547 TI - Trigonal splitting of a S6-state ion. PMID- 9997548 TI - Theoretical calculations of positron annihilation with rare-gas core electrons in simple and transition metals. PMID- 9997549 TI - Lattice position of Hf and Ta in LiNbO3: An extended x-ray-absorption fine structure study. PMID- 9997550 TI - Two-component superconductivity. II. Copper oxide high-Tc superconductors. PMID- 9997551 TI - Nonlinear sigma model and static holes. PMID- 9997553 TI - Orbital magnetism of singlet large bipolarons. PMID- 9997552 TI - Numerical computation of the flux-line-lattice structure of an inhomogeneous material in the London approximation. PMID- 9997554 TI - Chern-Simons gauge theories for the fractional-quantum-Hall-effect hierarchy and anyon superconductivity. PMID- 9997555 TI - Microwave-loss studies of organic superconductors. PMID- 9997556 TI - Superconducting transition temperature in a Nb/NbxSi1-x bilayer system. PMID- 9997557 TI - CeCu2Si2: More nearly magnetic than UBe13. PMID- 9997558 TI - Braid group and anyons on a cylinder. PMID- 9997559 TI - Frank-Read source-activated flux shear in type-II superconductors. PMID- 9997561 TI - Electron-energy-loss spectroscopy of layered systems. PMID- 9997560 TI - Theory of Hc1 and rho PMID- 9997562 TI - Ultrasonic wave propagation and barrier-limited heat flow in thin films of YBa2Cu3O7-x. PMID- 9997563 TI - Electrodynamics of moving superconductors and superconductors under the influence of external forces. PMID- 9997564 TI - Charging-energy corrections to macroscopic quantum tunneling in small Josephson junctions. PMID- 9997565 TI - Large bipolarons in two and three dimensions. PMID- 9997566 TI - Field dependence of the resistive transition for a square wire network. PMID- 9997567 TI - Disorder in a resistor network and the influence of disorder on the occurrence of superconductivity in thin granular metal films. PMID- 9997568 TI - Current-voltage characteristic of double normal tunnel junctions. PMID- 9997569 TI - Magnetic relaxation in an isotropic extreme type-II superconductor. PMID- 9997570 TI - Thermodynamic considerations and the phase diagram of superconducting UPt3. PMID- 9997571 TI - Coefficients of the second viscosity in thin liquid-helium films. PMID- 9997573 TI - Model for an extra phonon mode in La2CuO4 and La2NiO4. PMID- 9997572 TI - I-V characteristics of a circularly symmetric annular Josephson junction. PMID- 9997574 TI - Modeling oxygen isotope shifts and line-broadening effects of the 502-cm-1 Raman mode of YBa2Cu3O7-x. PMID- 9997576 TI - Boundary-condition effects on the superconducting transition temperature of proximity-effect systems. PMID- 9997575 TI - Interpretation of the temperature dependence of the electromagnetic penetration depth in YBa2Cu3O7- delta. PMID- 9997577 TI - Fermi surface in YBa2Cu3O6.9: Evidence from angle-resolved photoemission spectroscopy and positron two-dimensional angular correlation of annihilation radiation. PMID- 9997578 TI - Theory of nuclear relaxation in La2CuO4. PMID- 9997579 TI - Temperature dependence of the lower critical field and strong pinning in high temperature superconductors. PMID- 9997580 TI - Resistivity and thermoelectric-power measurements of PrxY1-xBa2Cu3O7- delta up to 1200 K and an electronic-structure analysis. PMID- 9997581 TI - Surface composition of clean, epitaxial thin films of YBa2Cu3O7-x from quantitative x-ray photoemission spectroscopy analysis. PMID- 9997582 TI - Thermal fluctuations and phase transitions in the vortex state of a layered superconductor. PMID- 9997583 TI - Model for the reversible magnetization of high- kappa type-II superconductors: Application to high-Tc superconductors. PMID- 9997584 TI - Temperature-independent, constant E-J relation below Tc in the current-induced resistive state of polycrystalline YBa2Cu3O7-x. PMID- 9997585 TI - Phonon anomalies and structural stability in the R2-xCexCuO4 system (R=Gd,Sm,Nd,Pr). PMID- 9997586 TI - Two observable features of the staggered-flux phase at nonzero doping. PMID- 9997587 TI - Anisotropic electromagnetic features of a grain-aligned YBa2Cu3Ox bulk superconductor. PMID- 9997588 TI - Effects of Zn substitution for Cu on superconducting and normal-state properties of (La,Sr)2CuO4, (Nd,Ce,Sr)2CuO4, and (Nd,Ce)2CuO4. PMID- 9997589 TI - Vortex-lattice-vortex-liquid states in anisotropic high-Tc superconductors. PMID- 9997590 TI - Calculations of the electronic structure and superconducting properties of BaPb1 xSbxO3. PMID- 9997591 TI - Magnetoconductance of Tl2Ba2CaCu2Ox films in the fluctuation regime. PMID- 9997592 TI - Critical fields and critical currents of superconducting disks in transverse magnetic fields. PMID- 9997594 TI - Polarons in the layered electron gas. PMID- 9997593 TI - Resistive loss at 10 GHz in c-axis-aligned in-situ-grown YBa2Cu3O7 films. PMID- 9997595 TI - Vortex-motion dissipation in high-Tc superconductors at microwave frequencies. PMID- 9997597 TI - Numerical simulation of flux creep through superconducting networks. PMID- 9997596 TI - Flux creep in high-Tc superconductors. PMID- 9997598 TI - Flux-creep dissipation in epitaxial YBa2Cu3O7- delta film: Magnetic-field and electrical-current dependence. PMID- 9997600 TI - Upper bound on the ratio of Ginzburg-Landau parameters kappa 2/ kappa for layered superconductors near Tc. PMID- 9997599 TI - Apex oxygen and critical temperature in copper oxide superconductors: Universal correlation with the stability of local singlets. PMID- 9997601 TI - 63Cu NMR and hole depletion in the normal state of yttrium-rich Y1-xPrxBa2Cu3O7. PMID- 9997602 TI - Magnetic relaxation, current-voltage characteristics, and possible dissipation mechanisms for high-Tc superconducting thin films of Y-Ba-Cu-O. PMID- 9997603 TI - Raman scattering from spin fluctuations in Pr2-xCexCuO4-y, Nd2-xCexCuO4-y, and Sm2-xCexCuO4-y. PMID- 9997604 TI - Positive Hall coefficient observed in single-crystal Nd2-xCexCuO4- delta at low temperatures. PMID- 9997605 TI - Infrared reflectivity of single-crystal Bi2Mm+1ComOy (M=Ca,Sr,Ba; m=1,2), Bi2Sr3Fe2O9.2, and Bi2Sr2MnO6.25, isomorphic to Bi-Cu-based high-Tc oxides. PMID- 9997607 TI - Monte Carlo studies of percolation in a superconducting array. PMID- 9997606 TI - Evidence for a time-dependent crossover from surfacelike to bulklike flux relaxation in YBa2Cu3O7- delta. PMID- 9997609 TI - Electronic structure of twin boundaries in YBa2Cu3O7. PMID- 9997608 TI - Initial crystallization of Bi4Ca3Sr3Cu4Oy glasses. PMID- 9997610 TI - Electronic structure and correlations of high-temperature superconducting compounds. PMID- 9997612 TI - O 1s core levels in Bi2Sr2CaCu2O8+ delta single crystals. PMID- 9997611 TI - Role of Van Hove singularity in high-temperature superconductors: Mean field. PMID- 9997613 TI - Neutron-irradiation effects on critical current densities in single-crystalline YBa2Cu3O7- delta. PMID- 9997614 TI - Spin and charge excitations of the degenerate Hubbard model in one dimension. PMID- 9997615 TI - Low-temperature specific heat of NbSe3: A reassessment. PMID- 9997616 TI - Structural and magnetic properties of Er thin films and Er/Y superlattices: Magnetoelastic effects. PMID- 9997618 TI - Numerical study of an effective interface model for the growth of wetting layers. PMID- 9997617 TI - Surface electronic structure of Ce in the alpha and gamma phase. PMID- 9997619 TI - High-resolution study of conductivity and cell potential versus doping concentration in potassium-doped polyacetylene: Correlation with structural transitions. PMID- 9997621 TI - Quasi-two-dimensional ferromagnetism in polycrystalline Fe. PMID- 9997620 TI - Spin-flip scattering near the metal-to-insulator transition in Cd0.95Mn0.05Se:In. PMID- 9997622 TI - Substrate-induced magnetic ordering of rare-earth overlayers. PMID- 9997624 TI - Neutron-scattering study of the magnetic excitations of thulium metal. PMID- 9997623 TI - Fast-ion conduction in fluorite CaF2 studied by equilibrium and nonequilibrium molecular dynamics. PMID- 9997625 TI - Functional expansion of the Anderson and SU(N) models. PMID- 9997626 TI - Structural enhancement of single-particle diffusivity in phase-separating systems. PMID- 9997627 TI - Antiferromagnetism in Ce1-xLaxAl2Ga2 and Ce1-yYyAl2Ga2 Kondo-lattice systems. PMID- 9997628 TI - Diffraction profiles of xenon on graphite at low temperatures. PMID- 9997629 TI - Bose condensation in quasi-one-dimensional antiferromagnets in strong fields. PMID- 9997631 TI - Shear stiffness C55 in A2BX4 crystals studied within the soliton model. PMID- 9997630 TI - Interpretation of a Schrodinger-like equation derived from a non-Markovian process. PMID- 9997632 TI - Lower bounds of the ground-state energy of the charged Bose gas. PMID- 9997633 TI - History dependence of a two-level system. PMID- 9997634 TI - General validity of Jastrow-Laughlin wave functions. PMID- 9997636 TI - Finite-size scaling and Monte Carlo simulations of first-order phase transitions. PMID- 9997635 TI - Photoemission study of the upper limit to the change of the local exchange splitting at finite temperature. PMID- 9997637 TI - Exact solutions for two interacting particles in a one-dimensional ring with a magnetic flux. PMID- 9997639 TI - Spin waves, phonons, and crystal-field excitations in thulium. PMID- 9997638 TI - Muon diffusion and spin dynamics in copper. PMID- 9997640 TI - Spin-wave modes in layered magnetic sandwich structures. PMID- 9997642 TI - Quantum stabilization of the Belavin-Polyakov soliton. PMID- 9997641 TI - Magnetoelastic anomalies in Fe-Ni Invar alloys. PMID- 9997644 TI - Spontaneous dimerization in quantum-spin chains. PMID- 9997643 TI - Estimation of the critical concentration in an anisotropic percolation network. PMID- 9997645 TI - Structural fluctuations in glass-forming liquids: Mossbauer spectroscopy on iron in glycerol. PMID- 9997647 TI - Interplay between one- and two-dimensional fluctuations for a class of XY models. PMID- 9997646 TI - Spin saturation of the random antiferromagnet (Cd,Mn)Te in magnetic fields to 150 T. PMID- 9997648 TI - Spin Jastrow state. PMID- 9997649 TI - Continuum limit in random sequential adsorption. PMID- 9997650 TI - Magnetic and thermal hysteresis in the O(N)-symmetric ( Phi 2)3 model. PMID- 9997652 TI - Micromagnetics of domain walls at surfaces. PMID- 9997651 TI - Short-range magnetic ordering in the highly frustrated pyrochlore Y2Mn2O7. PMID- 9997653 TI - Long-range order in a three-dimensional random-tiling quasicrystal. PMID- 9997655 TI - Numerical study of a Langevin model for the growth of wetting layers. PMID- 9997654 TI - Stress-induced metal-to-nonmetal transition in the quasi-one-dimensional superconductor Tl2Mo6Se6. PMID- 9997657 TI - Mechanical stability of simple planar lattices. PMID- 9997656 TI - Magnetic anisotropy of cubic iron-based diluted magnetic semiconductors. PMID- 9997658 TI - Lattice softening and melting characteristics of granular particles. PMID- 9997660 TI - Onsager reaction terms for quantum many-body systems: Application to antiferromagnetic and superconducting order in the Hubbard model. PMID- 9997659 TI - Gauge invariance and absence of exact conductance quantization in quantum ballistic transport. PMID- 9997662 TI - Solitons in a nonlinear elastic medium. PMID- 9997661 TI - Size dependence of coherent anomalies in self-consistent cluster approximations. PMID- 9997663 TI - Compensating holes in Ca2+-doped yttrium iron garnet and their influence on magnetic properties of the system. PMID- 9997664 TI - Surface melting away from equilibrium. PMID- 9997665 TI - Temperature and pressure constraints near the freezing point. PMID- 9997666 TI - Interatomic magnetic interactions in iron. PMID- 9997667 TI - Exact results for the spherical model with competing interactions on the Bethe lattice. PMID- 9997668 TI - Dipole-exchange modes in thin ferromagnetic films with strong out-of-plane anisotropies. PMID- 9997669 TI - Phase diagram of the t-J model: A semiclassical calculation. PMID- 9997670 TI - Estimation of the potential barrier of SCN--group reorientation in a potassium thiocyanate crystal using laser Raman spectroscopy. PMID- 9997671 TI - Spatiotemporal dynamics in a chain of damped spins. PMID- 9997672 TI - Two-dimensional spin-1/2 Heisenberg antiferromagnet: A quantum Monte Carlo study. PMID- 9997673 TI - Dynamics of patterns in ferroelastic-martensitic transformations. I. Lattice model. PMID- 9997674 TI - Dynamics of patterns in ferroelastic-martensitic transformations. II. Quasicontinuum model. PMID- 9997675 TI - Electron-phonon coupling in mixed-valence systems. PMID- 9997676 TI - Multifractality of conductance jumps in percolation. PMID- 9997677 TI - Phenomenological application of the projection-operator method and its connection with critical dynamics. PMID- 9997678 TI - Quantum corrections in an antiferromagnet: A systematic diagrammatical treatment of the Hubbard model. PMID- 9997679 TI - Nonreciprocal reflection from semi-infinite antiferromagnets. PMID- 9997681 TI - Unbinding transition of the interface of a two-dimensional Ising-model system with a defect zone in the bulk. PMID- 9997680 TI - Scaling hypothesis and nonzero-field critical invariants. PMID- 9997682 TI - Fluorescence line narrowing in Cr3+-doped gallium gadolinium garnet under a magnetic field. PMID- 9997683 TI - Pressure dependence of spin fluctuations in metallic glasses Ni25Zr75 and Fe100 xZrx (x=75,80). PMID- 9997684 TI - Superconductivity in an external magnetic field as a finite-size system. PMID- 9997685 TI - Two-component Fermi-liquid theory and infrared anomalies in CePd3 and YBa2Cu3O7. PMID- 9997686 TI - Slope discontinuity and fluctuation of lattice expansion near Tc in untwinned YBa2Cu3O7- delta single crystals. PMID- 9997688 TI - Fermi surface and electron-positron momentum density in YBa2Cu3O7. PMID- 9997687 TI - Electrical resistivity of the heavy-fermion system CePtSi under pressure. PMID- 9997689 TI - Satellites from hybridized Cu-O states in YBa2Cu3O7. PMID- 9997690 TI - Potentiometric method of estimating the critical temperature of the superconducting transition in high-Tc materials. PMID- 9997692 TI - Binding of holes in two-dimensional lattices with different boundary conditions. PMID- 9997691 TI - Valence state of copper in Nd2-xCexCuO4. PMID- 9997693 TI - Irreversibility in Ba0.625K0.375BiO3. PMID- 9997695 TI - Magnetic short-range order in CuO2 planes of high-Tc superconductors. PMID- 9997694 TI - Time-dependent Meissner fraction as a function of aging in an oxygen-deficient YBa2Cu3O7- delta single crystal. PMID- 9997696 TI - Origin of the Ba core-level binding-energy difference between tetragonal and orthorhombic YBa2Cu3O7- delta. PMID- 9997697 TI - Kinetics of ordering for correlated initial conditions. PMID- 9997698 TI - Lanczos calculation for the s=1/2 antiferromagnetic Heisenberg chain up to N=28 spins. PMID- 9997700 TI - Spontaneous dimerization in the ground state of one-dimensional frustrated Heisenberg antiferromagnets. PMID- 9997699 TI - Magnetic susceptibility of the strongly correlated Hubbard model. PMID- 9997701 TI - Cubic zero-field splitting and site symmetry of Mn2+ in ZnS. PMID- 9997703 TI - Theory of Shapiro steps in Josephson-junction arrays and their topology. PMID- 9997702 TI - Influence of finite coherence length of incoming light on enhanced backscattering. PMID- 9997705 TI - Evaporation of a single vortex line in a weakly coupled multilayered superconductor. PMID- 9997704 TI - Magnetically modulated microwave absorption in the organic superconductor kappa (BEDT-TTF)2Cu(NCS)2 PMID- 9997706 TI - Tunneling measurement of the electron inelastic-scattering rate in a strongly disordered superconductor. PMID- 9997707 TI - Power-law temperature dependence of the inelastic-scattering rate in disordered superconductors. PMID- 9997708 TI - Negative local superfluid densities: The difference between dirty superconductors and dirty Bose liquids. PMID- 9997709 TI - Single-band model of normal-state transport properties of high-Tc copper oxides. PMID- 9997710 TI - ac absorption in the high-Tc superconductors: Reinterpretation of the irreversibility line. PMID- 9997711 TI - Anisotropy of low-energy electronic Raman scattering in YBa2Cu3O7. PMID- 9997713 TI - Role of grains and weak links in the nonlinear magnetic response of Y-Ba-Cu-O. PMID- 9997712 TI - Role of anisotropy in the dissipative behavior of high-temperature superconductors. PMID- 9997714 TI - Raman investigation of the YBa2Cu3O7 imaginary response function. PMID- 9997715 TI - Ordering in high-Tc superconducting systems: Effective pair interactions in Y-Ba Cu-O. PMID- 9997716 TI - Optical absorption in strong-coupling-limit Hubbard models. PMID- 9997717 TI - Splitting of a domain wall near the diamagnetic phase transition. PMID- 9997718 TI - Roughening of flat domain walls by random strain fields: Neutron-scattering study of twinned orthorhombic Dy(AsxV1-x)O4. PMID- 9997719 TI - Prediction of logarithmic growth in a quenched Ising model. PMID- 9997720 TI - Ground state of the two-dimensional antiferromagnetic Heisenberg model studied using an extended Wigner-Jordon transformation. PMID- 9997721 TI - Path-integral approach to the Hubbard model. PMID- 9997723 TI - Orientational ordering of a cesium monolayer on graphite. PMID- 9997722 TI - Mechanical strength of highly porous ceramics. PMID- 9997724 TI - Multiple-scattering theory of magnetic x-ray circular dichroism. PMID- 9997725 TI - Theory of the local density of surface states on a metal: Comparison with scanning tunneling spectroscopy of a Au(111) surface. PMID- 9997726 TI - Alkali-metal segregation at glass surfaces during electron irradiation. PMID- 9997727 TI - Polarization dependence of multiphoton transitions. PMID- 9997728 TI - Conductance of a disordered narrow wire in a strong magnetic field. PMID- 9997729 TI - First-principles molecular-dynamics simulation of liquid and amorphous selenium. PMID- 9997731 TI - Energy and angular distributions of 100- to 400-eV Na+ scattered from Cu(110). PMID- 9997730 TI - Oxygen adsorption on a NbC0.9(111) surface: Angle-resolved photoemission study. PMID- 9997732 TI - Surface localized states and the Fermi contour of Pd(001). PMID- 9997733 TI - Factors mediating smoothness in epitaxial thin-film growth. PMID- 9997734 TI - Multiply twinned structures in unsupported ultrafine silver particles observed by electron diffraction. PMID- 9997735 TI - Correlation energy and the virial theorem. PMID- 9997736 TI - Surface-phonon dispersion investigation of the (1 x 1)-->(5 x 1) reconstruction of the Ir(100) surface. PMID- 9997737 TI - Electron-phonon scattering times in thin Sb films. PMID- 9997739 TI - The Benedicks effect: Nonlocal electron transport in metals. PMID- 9997738 TI - Conductivity of random resistor networks: An investigation of the accuracy of the effective-medium approximation. PMID- 9997741 TI - Atomic and electronic structure of Fe films grown on Pd{001} PMID- 9997740 TI - Resonant Raman scattering in a quasi-one-dimensional ZrS3 crystal. PMID- 9997742 TI - Planar diffusion constant Da in acceptor-graphite intercalation compounds. PMID- 9997743 TI - Self-consistent electronic structure of 3d-transition-metal impurities in aluminum using the recursion method. PMID- 9997744 TI - Electronic effects in the Mo(001) surface reconstruction: Two-dimensional Fermi surfaces and nonadiabaticity. PMID- 9997745 TI - Single-body methods in 3d transition-metal atoms. PMID- 9997746 TI - Image potential for an electron near an impenetrable surface. PMID- 9997747 TI - Rhodium monolayer on gold: A 4d ferromagnet. PMID- 9997749 TI - Transport along doping quantum wires in silicon. PMID- 9997748 TI - Eigenfunction-expansion method for solving the quantum-wire problem: Formulation. PMID- 9997751 TI - Coupled interface-plasmon modes of a superlattice and doped overlayer. PMID- 9997750 TI - Electronic structure of interstitial carbon in silicon. PMID- 9997752 TI - H-induced surface restructuring on Si(100): Formation of higher hydrides. PMID- 9997753 TI - Metallic impurity band in the narrow-band-gap semiconductor n-type InSb. PMID- 9997754 TI - Si(111)-(4 x 1)In surface reconstruction studied by impact-collision ion scattering spectrometry. PMID- 9997756 TI - Defect-state occupation, Fermi-level pinning, and illumination effects on free semiconductor surfaces. PMID- 9997755 TI - Defect relaxation in amorphous silicon: Stretched exponentials, the Meyer-Neldel rule, and the Staebler-Wronski effect. PMID- 9997757 TI - Exciton states in coupled double quantum wells in a static electric field. PMID- 9997758 TI - Exciton Stark ladder in semiconductor superlattices. PMID- 9997759 TI - Theory of bound polarons near interfaces of polar semiconductors. PMID- 9997760 TI - Band offset in GaAs/AlxGa1-xAs multiple quantum wells calculated with the sp3s* tight-binding model. PMID- 9997761 TI - Magnetoacoustic effects in n-type InSb: Magnetic freezeout and hopping conductivity at low temperatures. PMID- 9997762 TI - I-U dependence of TlInX2 (X=Se,Te) single crystals: The Ohmic and S-type regions. PMID- 9997763 TI - Electronic states in doped conducting polymers: Numerical simulation of disordered systems. PMID- 9997764 TI - Diamagnetic shift in InxGa1-xAs/GaAs strained quantum wells. PMID- 9997766 TI - Gap properties of AlnGa8-nAs8 ordered compounds. PMID- 9997765 TI - Hot-electron relaxations and hot phonons in GaAs studied by subpicosecond Raman scattering. PMID- 9997768 TI - Edge states in a circular quantum dot. PMID- 9997767 TI - Multiphonon hopping of carriers on defect clusters in an amorphous Ge-Sb-Se system. PMID- 9997769 TI - Quasiparticle calculation of the dielectric response of silicon and germanium. PMID- 9997770 TI - Oxygen complexes in silicon. PMID- 9997771 TI - Promotion of the Si(100)-O2 reaction by Sm. PMID- 9997772 TI - Pressure dependence of the energy gap in trans-polyacetylene. PMID- 9997773 TI - Pseudopotential calculations of the valence-band offsets at the ZnSe/Ge, ZnSe/GaAs, and GaAs/Ge (110) interfaces: Effects of the Ga and Zn 3d electrons. PMID- 9997774 TI - Contribution of polarons and bipolarons to low-temperature conductivity in doped polypyrrole. PMID- 9997775 TI - Effect of a magnetic field on the photoluminescence from InxGa1-xAs/GaAs and GaAs/AlxGa1-xAs quantum wells. PMID- 9997776 TI - Defect structure and recovery in hydrogen-implanted semi-insulating GaAs. PMID- 9997777 TI - Experimental determination of adsorbate-induced surface stress: Oxygen on Si(111) and Si(100). PMID- 9997778 TI - Many-particle effects and nonlinear optical properties of GaAs/(Al,Ga)As multiple quantum-well structures under quasistationary excitation conditions. PMID- 9997779 TI - Effect of scattering in electrodes on double-barrier resonant tunneling. PMID- 9997780 TI - Spin-orbit splitting of GaAs and InSb bands near Gamma. PMID- 9997782 TI - Amorphous Ge under pressure. PMID- 9997781 TI - Structural and magnetic properties of stage-2 EuCl3-graphite intercalation compound. PMID- 9997783 TI - Self-consistent Landau-level broadening by acoustic phonons in two-dimensional electron systems. PMID- 9997784 TI - Electrical properties of silicon point contacts. PMID- 9997785 TI - Quasiparticle properties of doped quantum-well systems. PMID- 9997786 TI - Local bonding structure of Sb on Si(111) by surface extended x-ray-absorption fine structure and photoemission. PMID- 9997787 TI - Collective electronic excitations in GaAs/AlxGa1-xAs quantum wells. PMID- 9997788 TI - Electric-field effects of the excitons in asymmetric triangular AlxGa1-xAs-GaAs quantum wells. PMID- 9997789 TI - Temperature dependence of the dielectric function and the interband critical point parameters of GaSb. PMID- 9997790 TI - Boron reactivation kinetics in hydrogenated silicon after annealing in the dark or under illumination. PMID- 9997791 TI - Electron localization and charge transport in poly(o-toluidine): A model polyaniline derivative. PMID- 9997792 TI - Conduction mechanism in PtSi/Si Schottky diodes. PMID- 9997794 TI - Ultrasonic attenuation and internal friction in (AgI)x(AgPO3)1-x superionic glasses. PMID- 9997793 TI - Proposed explanation of the p-type doping proclivity of ZnTe. PMID- 9997795 TI - Dynamics of a quadrupolar glass. PMID- 9997796 TI - Theoretical study of the interstice statistics of the oxygen sublattice in vitreous SiO2. PMID- 9997797 TI - Theoretical investigation of the motional states of the nitrite ion in alkali halide crystals. PMID- 9997799 TI - Self-consistent band structures, charge distributions, and optical-absorption spectra in MgO, alpha -Al2O3, and MgAl2O4. PMID- 9997798 TI - Anharmonic interactions in orientationally disordered molecular crystals: Fermi resonance in N2O. PMID- 9997800 TI - Effect of uniaxial pressure on the 222-K structural phase transition of hexagonal BaTiO3. PMID- 9997801 TI - Comparison of unreconstructed with reconstructed Ge8(GaAs)4 (001) superlattices. PMID- 9997802 TI - Optical Stark effects in the multiple exciton states at a stacking-fault plane in BiI3 crystals. PMID- 9997804 TI - Refractive-index change due to F color centers in KClxBr1-x mixed crystals. PMID- 9997803 TI - Femtosecond thermoreflectivity and thermotransmissivity of polycrystalline and single-crystalline gold films. PMID- 9997805 TI - Determination of the threshold voltage in sodium-doped metal-oxide-semiconductor structures. PMID- 9997807 TI - Laser-induced structural changes in magnetron-sputtered hydrogenated microcrystalline silicon films. PMID- 9997806 TI - Collective excitations in a spin-polarized quasi-two-dimensional electron gas. PMID- 9997808 TI - Free-energy model for bonding in amorphous covalent alloys. PMID- 9997809 TI - Intersubband absorption line broadening in semiconductor quantum wells: Nonparabolicity contribution. PMID- 9997810 TI - Theory of a grating coupler of finite thickness. PMID- 9997811 TI - Comment on the existence proofs of the Wannier-Stark ladder. PMID- 9997812 TI - Reply to "Comment on the existence proofs of the Wannier-Stark ladder" PMID- 9997813 TI - Erratum: Nonrelativistic zitterbewegung in two-band systems PMID- 9997814 TI - Pressure effects on the martensitic transformation in metallic sodium. PMID- 9997815 TI - Role of O2 negative-ion formation in low-energy electron-induced oxidation of InP(110). PMID- 9997816 TI - Observation of two-dimensional resonant magnetopolarons and phonon-assisted resonant tunneling in double-barrier heterostructures. PMID- 9997817 TI - Theoretical investigation of noise characteristics of double-barrier resonant tunneling systems. PMID- 9997818 TI - Relationship between interfacial superstructures and Schottky-barrier heights of Sb/GaAs contacts. PMID- 9997819 TI - Anharmonic self-energies of phonons in silicon. PMID- 9997820 TI - Charge state of hydrogen in crystalline silicon. PMID- 9997821 TI - Resonant tunneling in double-barrier quantum wells with a white-noise random potential: Heterogeneous elastic-broadening effects. PMID- 9997822 TI - Nonparametrized calculation of the electronic and vibrational structure of amorphous SiOx. PMID- 9997823 TI - Photoabsorption spectra of sodium clusters. PMID- 9997825 TI - First-principles study of the electronic properties of graphite. PMID- 9997824 TI - (7 x 1) reconstruction of the (112-bar0) surfaces of holmium and erbium. PMID- 9997826 TI - Electronic structure of hydrogen and oxygen chemisorbed on plutonium: Theoretical studies. PMID- 9997827 TI - Diffusion of desorbing adsorbate: Study of a mesoscopic model. PMID- 9997828 TI - Substrate effects on the surface-enhanced Raman spectrum of benzoic acid adsorbed on silver oblate microparticles. PMID- 9997829 TI - Comparative study of the electronic structure of ordered, partially ordered, and disordered phases of the Cu3Au alloy. PMID- 9997830 TI - Electronic structure in random hexagonal close-packed transition-metal alloys by the tight-binding linear-muffin-tin-orbital coherent-potential method. PMID- 9997831 TI - Crystallinity effects on the surface optical response in metals: A preliminary calculation. PMID- 9997832 TI - Resonant photoelectron spectroscopy at the Mo 4p-->4d absorption edge in MoS2. PMID- 9997833 TI - Stability comparison of several icosahedral structure units of Al-Cr alloys. PMID- 9997834 TI - Analytic embedded-atom potentials for fcc metals: Application to liquid and solid copper. PMID- 9997835 TI - X-ray photoemission and Auger energy shifts in some gold-palladium alloys. PMID- 9997836 TI - Structure and phases of the Au(111) surface: X-ray-scattering measurements. PMID- 9997837 TI - Femtosecond relaxation dynamics of image-potential states. PMID- 9997838 TI - Ab initio calculation of chemisorption systems: H on Pd(001) and Pd(110). PMID- 9997839 TI - High-resolution low-energy electron-diffraction analysis of the Pb(110) roughening transition. PMID- 9997840 TI - Roles of the attractive and repulsive forces in atomic-force microscopy. PMID- 9997841 TI - Tight-binding analysis of energy-band structures in quantum wires. PMID- 9997842 TI - Optical spectroscopic investigation of segmented trans-polyacetylene. PMID- 9997843 TI - Intersubband absorption in In0.53Ga0.47As/In0.52Al0.48As multiple quantum wells. PMID- 9997844 TI - Resonant tunneling via quantum bound states in a classically unbound system of crossed, narrow channels. PMID- 9997845 TI - Decay measurements of free- and bound-exciton recombination in doped GaAs/AlxGa1 xAs quantum wells. PMID- 9997846 TI - Time-resolved measurements of the radiative recombination in GaAs/AlxGa1-xAs heterostructures. PMID- 9997848 TI - Transient simulation of electron emission from quantum-wire structures. PMID- 9997847 TI - Tight-binding model for GaAs/AlAs resonant-tunneling diodes. PMID- 9997849 TI - Simple model of electric-dipole second-harmonic generation from interfaces. PMID- 9997850 TI - Auger-electron spectroscopy, electron-energy-loss spectroscopy, and x-ray photoemission spectroscopy studies of oxygen adsorption on the InP(111)-(1 x 1) surface. PMID- 9997851 TI - Optical anisotropy and Raman scattering from highly oriented poly(octylthiophene) films. PMID- 9997853 TI - Elliott's model and thermoreflectivity: Application to the layered structure ZrSe3. PMID- 9997852 TI - Irreversible changes in doping efficiency and hydrogen bonding in the equilibrium state of a-Si:H. PMID- 9997854 TI - Comparison of the phonon spectra of 70Ge and natural Ge crystals: Effects of isotopic disorder. PMID- 9997856 TI - Hot luminescence and Landau-level fine structure in bulk GaAs. PMID- 9997855 TI - Magnetotunneling analysis of the scattering processes in a double-barrier structure with a two-dimensional emitter. PMID- 9997857 TI - Effect of the X point on the escape of electrons from the quantum well of a double-barrier heterostructure. PMID- 9997858 TI - Local partial densities of states in Ni and Co silicides studied by soft-x-ray emission spectroscopy. PMID- 9997859 TI - Gap-state density of lightly P- and B-doped a-Si:H deduced from space-charge limited photocurrents. PMID- 9997860 TI - RbF as reactive and dipole interlayers between the Ge/GaAs interface. PMID- 9997861 TI - High-field transport in semiconductors. I. Absence of the intra-collisional-field effect. PMID- 9997863 TI - Phase diagram of the Fe1-xCoxSi2 alloy in the fluorite form. PMID- 9997862 TI - 4f7-4f7 transitions in Gd, oxidized Gd, and epitaxial Gd silicide. PMID- 9997864 TI - First-principles virtual-crystal calculations of AlxGa1-xAs disordered alloys and heterostructures: Band offsets and absolute alloy energies. PMID- 9997865 TI - Quasiparticle calculation of the electronic band structure of the (InAs)1/(GaAs)1 superlattice. PMID- 9997866 TI - Exact and approximate results for the polaron in one dimension. PMID- 9997867 TI - Angular dispersion and polarization mixing in GaAs/AlAs superlattices grown along the PMID- 9997868 TI - Experimental evidence for the transition from two- to three-dimensional behavior of excitons in quantum-well structures. PMID- 9997869 TI - Nonelectronic scattering of longitudinal-optical phonons in bulk polar semiconductors. PMID- 9997870 TI - Type-I and type-II Stark-ladder phenomena in Ga1-xInxAs-GaAs strained-layer superlattices. PMID- 9997871 TI - Three-dimensional electrons and two-dimensional electric subbands in the transport properties of tin-doped n-type indium selenide: Polar and homopolar phonon scattering. PMID- 9997872 TI - Elastic scattering of acoustic phonons in Si. PMID- 9997873 TI - Theory of mesoscopic tunnel junctions: From shot noise to the standard quantum limit. PMID- 9997874 TI - Electron density of states of CdTe. PMID- 9997875 TI - High-pressure investigation of GaSb and Ga1-xInxSb/GaSb quantum wells. PMID- 9997877 TI - Quantum network theory of transport with application to the generalized Aharonov Bohm effect in metals and semiconductors. PMID- 9997876 TI - Strain relaxation during the initial stages of growth in Ge/Si(001). PMID- 9997879 TI - Temporal characteristics of electron tunneling in double-barrier stepped-quantum well structures. PMID- 9997878 TI - Theory of the thermal expansion of Si and diamond. PMID- 9997880 TI - Energy-level structure of two-dimensional electrons confined at the AlxGa1 xAs/GaAs interface studied by photoluminescence excitation spectroscopy. PMID- 9997881 TI - Anharmonic potentials and vibrational localization in glasses. PMID- 9997882 TI - Interaction between alkali-metal ions M+ in the deactivation process of quartz embedded Al-M+ centers. PMID- 9997883 TI - Surface effects on the electrodiffusion of alkali-metal ions and protons in quartz. PMID- 9997884 TI - Surface core exciton in LiCl studied by photoelectron spectroscopy. PMID- 9997885 TI - Interatomic force fields for silicas, aluminophosphates, and zeolites: Derivation based on ab initio calculations. PMID- 9997886 TI - KA2 and KA1 bands in FA(II) KCl:Li crystals. PMID- 9997887 TI - Optical properties of diamond. PMID- 9997888 TI - Electronic structure of nickel, iron, and cobalt impurities in magnesium oxide. PMID- 9997889 TI - Substitution effects on bipolarons in alkoxy derivatives of poly(1,4-phenylene vinylene). PMID- 9997890 TI - Band-structure methods for incommensurably modulated crystals: Application to the low-temperature phase of tetrathiafulvalene-tetracyanoquinodimethane (TTF-TCNQ). PMID- 9997891 TI - Efficient ab initio molecular-dynamics simulations of carbon. PMID- 9997892 TI - Diffraction and focusing effects in the elastic scattering of electrons from Cu(001). PMID- 9997893 TI - Hydrogen ordering and local mode in alpha -LuDx at low concentrations. PMID- 9997894 TI - Dislocation core studies in empirical silicon models. PMID- 9997895 TI - Variational method in a heterojunction. PMID- 9997897 TI - Electron-phonon interaction in a quantum well. PMID- 9997896 TI - Electrodynamic response of a harmonic atom in an external magnetic field. PMID- 9997898 TI - Binding energy of the barbell exciton. PMID- 9997899 TI - Raman scattering from the intrinsic 68-meV acceptor in Ga-rich GaAs. PMID- 9997900 TI - Comment on "Existence of Wannier-Stark localization" PMID- 9997901 TI - Reply to "Comment on 'Existence of Wannier-Stark localization' " PMID- 9997902 TI - Comment on "Self-diffusion in tungsten" PMID- 9997903 TI - Surface core-level spectroscopy of Cu(100) and Al(100). PMID- 9997904 TI - Thickness-dependent thin-film resistivity: Application of quantitative scanning tunneling-microscopy imaging. PMID- 9997905 TI - Symmetry-breaking relaxation of vacancies on Si(111)2 x 1. PMID- 9997907 TI - Microscopic symmetry properties of (001) Si/Ge monolayer superlattices. PMID- 9997906 TI - Spin-dependent conductivity in amorphous hydrogenated silicon. PMID- 9997908 TI - Magnetoresistance oscillations in a grid potential: Indication of a Hofstadter type energy spectrum. PMID- 9997909 TI - Resonant interband tunneling via Landau levels in polytype heterostructures. PMID- 9997910 TI - Nonlinear feedback oscillations in resonant tunneling through double barriers. PMID- 9997911 TI - Stark quantization in superlattices. PMID- 9997912 TI - Transient dynamics in excitonic optical bistability in polymers. PMID- 9997913 TI - Incoherent neutron scattering in acetanilide and three deuterated derivatives. PMID- 9997914 TI - Properties of the 800-nm luminescence band in neutron-irradiated magnesium oxide crystals. PMID- 9997916 TI - Radiation-induced amorphization of ordered intermetallic compounds CuTi, CuTi2, and Cu4Ti3: A molecular-dynamics study. PMID- 9997915 TI - Spectroscopy of Cr3+ and Cr4+ ions in forsterite. PMID- 9997917 TI - Dependence of the heavy-ion-induced desorption yield on the primary-ion energy loss. PMID- 9997918 TI - Critical evaluation of Eu valences from LIII-edge x-ray-absorption and Mossbauer spectroscopy of EuNi2Si2-xGex. PMID- 9997919 TI - Prediction of high-temperature superconductivity in hexagonal and rhombohedral phases of metallic hydrogen. PMID- 9997920 TI - Preparation and characterization of layered superconductors. PMID- 9997922 TI - Superconducting proximity effect in inhomogeneous media. PMID- 9997921 TI - Quantized voltage plateaus in Josephson-junction arrays: A numerical study. PMID- 9997924 TI - Variational calculations of bipolaron binding energies. PMID- 9997923 TI - 200-keV He+-ion irradiation effects on the properties of pulsed-laser-deposited YBa2Cu3O7-x thin films. PMID- 9997925 TI - Charge and vortex dynamics in arrays of tunnel junctions. PMID- 9997926 TI - Energy-transport phenomena in single superconducting grains. PMID- 9997927 TI - Phonons and rotons in commensurate p-H2 and o-D2 monolayers on graphite. PMID- 9997929 TI - Magnetic properties of the charged Anderson-Brinkman-Morel state: Absence of Hc1. PMID- 9997928 TI - Spin dynamics in a polarized Bose gas. PMID- 9997931 TI - Magnetic-field dependence of the critical current in long Josephson junctions. PMID- 9997930 TI - Gap function and density of states in the strong-coupling limit for an electron boson system. PMID- 9997932 TI - London penetration depth of d-wave superconductors. PMID- 9997934 TI - Superfluidity of 4He. PMID- 9997933 TI - Duality symmetry and power-law fading of frustration in a quantum multiconnected superconductor. PMID- 9997936 TI - Quantum dynamics of a two-state system in a dissipative environment. PMID- 9997937 TI - Josephson-junction dynamics in the presence of a localized magnetic inhomogeneity. PMID- 9997935 TI - Optical studies of single-crystal Nd2-xCexCuO4- delta. PMID- 9997938 TI - Thickness dependence of the irreversibility line in YBa2Cu3O7-x thin films. PMID- 9997939 TI - Low-temperature specific heat of the Y1-xPrxBa2Cu3O7- delta system. PMID- 9997940 TI - Analysis of large-area twins in Bi2CaSr2Cu2O8 superconductors. PMID- 9997942 TI - Phonon spectra and lattice specific heats of the thallium-based high-temperature superconductors. PMID- 9997943 TI - Acoustic study of YBa2Cu3Ox thin films. PMID- 9997941 TI - Localization and interaction effects during superconductor-insulator transition of Bi2Sr2Ca1-xGdxCu2O8+d. PMID- 9997944 TI - Weak ferromagnetism and canting in BiPbSr2MnO6 and BiPbCa2MnO6. PMID- 9997945 TI - Quasiparticle and vortex in the anyon gas. PMID- 9997946 TI - Magnetism and superconductivity in 3d-metal-substituted Bi-based cuprates having the 2:2:0:1 structure. PMID- 9997947 TI - Site selectivity and cation diffusion in YBa2Cu3O7- delta. PMID- 9997948 TI - Optical properties and Fermi-surface nesting in superconducting oxides. PMID- 9997949 TI - Determination of the local structure in Ba1-xKxBiO3 by x-ray-absorption spectroscopy. PMID- 9997950 TI - Irreversibility temperatures in superconducting oxides: The flux-line-lattice melting, the glass-liquid transition, or the depinning temperatures. PMID- 9997952 TI - Electron-hole pairing and anomalous properties of layered high-Tc compounds. PMID- 9997951 TI - Ultrasonic evidence of strong vibrational anharmonicity in high-Tc superconductors and its effect on determination of their elastic properties. PMID- 9997954 TI - Electron-hole liquid model for high-Tc superconductors: Metal-insulator transition and doping behavior. PMID- 9997953 TI - Neutron-scattering study of spin fluctuations in superconducting YBa2Cu3O6+x (x=0.40,0.45,0.50). PMID- 9997955 TI - Statistical transmutation in diluted flux states. PMID- 9997957 TI - Rotation of polarized light reflected from T- and P-violating phases. PMID- 9997956 TI - Variational Monte Carlo study of generalized flux phases in the t-J model. PMID- 9997958 TI - Dynamical Jahn-Teller effect as a possible microscopic mechanism for anyonic superconductivity. PMID- 9997959 TI - Superconductivity in an anisotropic three-dimensional narrow-band system. PMID- 9997960 TI - Relation between the electronic structure and the superconductivity of cuprates as revealed by Cu 2p photoemission and theoretical investigations. PMID- 9997961 TI - Anisotropic three-dimensional t-J model. PMID- 9997962 TI - Antiferromagnetism in three-band Hubbard model: Local-ansatz approach. PMID- 9997963 TI - Symmetry modes, competing interactions, and universal description for modulated phases in the dielectric A2BX4 family. PMID- 9997964 TI - Calculated magnetic properties of the antiferromagnetic UNiSn compound. PMID- 9997965 TI - Correlation functions of the one-dimensional Hubbard model in a magnetic field. PMID- 9997966 TI - Polarization and resonance studies of x-ray magnetic scattering in holmium. PMID- 9997967 TI - Neutron-diffraction study of magnetic ordering in the pyrochlore series R2Mo2O7 (R=Nd,Tb,Y). PMID- 9997968 TI - Short-range magnetic ordering in the highly frustrated pyrochlore systems FeF3 and Mn2Sb2O7. PMID- 9997970 TI - Diamagnetism in the dissipative regime. PMID- 9997971 TI - Optical properties of Rochelle salt. PMID- 9997969 TI - Stabilization of breathers in a parametrically driven sine-Gordon system with loss. PMID- 9997973 TI - Thermal conductivity of solid H2 in the orientationally ordered phase. PMID- 9997972 TI - Specific heat of Cd1-xCoxS and Cd1-xCoxSe at low temperatures. PMID- 9997974 TI - Anomalous electric and heat current in charge- and spin-density waves. PMID- 9997975 TI - Local fields in random dielectrics: Distribution characteristics and the effects of microstructure. PMID- 9997976 TI - Theory of unstable growth. II. Conserved order parameter. PMID- 9997977 TI - Electronic diamagnetism in a three-dimensional lattice. PMID- 9997978 TI - High phase-transition temperature for beta -AgI to alpha -AgI and an explanation of the memory effect. PMID- 9997979 TI - Reweighting in Monte Carlo and Monte Carlo renormalization-group studies. PMID- 9997980 TI - Magnetic properties of Ni(NO3)2 PMID- 9997982 TI - Renormalization-group theory of the incommensurate pinning transition and threshold dynamics. PMID- 9997981 TI - Correlation length and free energy of the S=1/2 XYZ chain. PMID- 9997983 TI - Structural phase transition of high-stage MoCl5 graphite intercalation compounds. PMID- 9997984 TI - Brillouin-scattering study of the liquid-glass transition in supercooled aqueous lithium chloride solutions: Generalized hydrodynamics and mode-coupling analyses. PMID- 9997985 TI - Critical dynamics of planar ferromagnets. PMID- 9997986 TI - Potts models: Density of states and mass gap from Monte Carlo calculations. PMID- 9997988 TI - Effective-action approach to the frustrated Heisenberg antiferromagnet in two dimensions. PMID- 9997987 TI - Magnetic properties of neodynium atoms in Nd-Fe multilayers studied by magnetic x ray dichroism on Nd LII and Fe K edges. PMID- 9997989 TI - Variational theorem for vector-mean-field theories of statistical transmutation. PMID- 9997990 TI - General solution of the Landau-Lifshitz-Gilbert equations linearized around a Bloch wall. PMID- 9997991 TI - Theory of quasiperiodic lattices. I. Scaling transformation for a quasiperiodic lattice. PMID- 9997993 TI - Electronic structures and magnetic moments of Fe3+ySi1-y and Fe3-xVxSi alloys with DO3-derived structure. PMID- 9997992 TI - Theory of quasiperiodic lattices. II. Generic trace map and invariant surface. PMID- 9997995 TI - Large-S analysis of a quantum axial next-nearest-neighbor Ising model in one dimension. PMID- 9997994 TI - Discrete scatterers and autocorrelations of multiply scattered light. PMID- 9997997 TI - Quantum Monte Carlo simulation method for spin systems. PMID- 9997996 TI - Wave functions and other properties of spin-reversed quasiparticles at nu =1/m Landau-level occupation. PMID- 9997998 TI - Electron correlations in a multivalley electron gas and Fermion-boson conversion. PMID- 9997999 TI - Quasiparticle properties of the electron gas at metallic densities in the effective-potential expansion method. PMID- 9998000 TI - Motion of vortex pairs in the ferromagnetic and antiferromagnetic anisotropic Heisenberg model. PMID- 9998002 TI - Spin-wave theory of two-dimensional ferromagnets in the presence of dipolar interactions and magnetocrystalline anisotropy. PMID- 9998001 TI - Monte Carlo investigation of critical dynamics in the three-dimensional Ising model. PMID- 9998003 TI - ESR of Gd and Er impurities in the metallic Van Vleck compound TmH2. PMID- 9998005 TI - Chemical and magnetic ordering in amorphous systems. PMID- 9998004 TI - Perturbed magnetic ordering in the disordered spinel ZnxCo1-xFeCrO4. PMID- 9998007 TI - Hartree model of electrons in a two-dimensional Wigner lattice on a dielectric substrate. PMID- 9998006 TI - High-temperature resistivity minima in Co-rich amorphous ferromagnets. PMID- 9998008 TI - Vibrational entropy effects at a diffusionless first-order solid-to-solid transition. PMID- 9998009 TI - Polaronic effects in mixed-valence systems at finite temperatures. PMID- 9998010 TI - Effect of spin ordering on bound states in dilute alloys. PMID- 9998011 TI - High-accuracy Monte Carlo study of the three-dimensional classical Heisenberg ferromagnet. PMID- 9998012 TI - Self-consistent solutions of the Thomas-Fermi-Dirac equation including gradient and correlation corrections. PMID- 9998013 TI - Holes and magnetic textures in the two-dimensional Hubbard model. PMID- 9998014 TI - Surface magnetic properties of a semi-infinite Ising model with a spin-1 free surface. PMID- 9998015 TI - Sputtering of atoms and excimers upon self-trapping of excitons in solid krypton. PMID- 9998016 TI - Possible microscopic model for superconductivity in UPt3. PMID- 9998017 TI - Meissner effect and oscillatory penetration of a magnetic field from the pairing of valence and conduction electrons. PMID- 9998018 TI - Residual surface resistance of polycrystalline superconductors. PMID- 9998019 TI - Commensurate-flux-phase state of the t-J model. PMID- 9998020 TI - Self-consistent treatment for strong localization of light in disordered dielectric superlattices. PMID- 9998021 TI - Excitation spectrum of a superconducting sphere in a superconducting host: Effects of phase fluctuations. PMID- 9998022 TI - Collective modes of an anyon gas on a lattice. PMID- 9998023 TI - Anisotropic magnetic-field dependence of the specific heat in single-crystal-like YBa2Cu3O7-x. PMID- 9998024 TI - Quasi-irreversibility temperature in a type-I superconductor. PMID- 9998025 TI - Mechanism for high-temperature superconductivity in cuprates. PMID- 9998027 TI - Orientational phase transitions in systems of adsorbed molecules. PMID- 9998026 TI - Orbital-resolved partial density of states in YBa2Cu3O7. PMID- 9998028 TI - hcp-bcc transition and the free energies of the hcp and bcc structures of zirconium. PMID- 9998029 TI - Anomalous magnetic behavior in pseudobinary compounds of CeFe2. PMID- 9998031 TI - Modified spin-wave theory of low-dimensional quantum spiral magnets. PMID- 9998030 TI - Specific-heat study of the structural phase transition in BaMnF4. PMID- 9998032 TI - Phase diagram of the spin-1/2 Heisenberg antiferromagnet on a square lattice with nearest- and next-nearest-neighbor couplings. PMID- 9998034 TI - Molecular-dynamics calculation of shear-mediated instability in a two-dimensional solid. PMID- 9998033 TI - Percolation renormalization-group approach to the hard-square model. PMID- 9998035 TI - d-wave, dimer, and chiral states in the two-dimensional Hubbard model. PMID- 9998036 TI - X-ray-diffraction study of the equation of state and the phase transition in cesium iodide at nearly hydrostatic pressure. PMID- 9998037 TI - Surface thermodynamic properties of a semi-infinite Ising ferromagnet in the presence of a surface transverse field. PMID- 9998038 TI - First-principles study of the lattice dynamics of K2SO4. PMID- 9998039 TI - Gutzwiller approach to the negative-U Hubbard model. PMID- 9998040 TI - Erratum: Electromagnetic response of generalized flux phases in the t-J model PMID- 9998041 TI - Skyrmion excitation in the infinite-U Hubbard model. PMID- 9998042 TI - Local tunneling spectroscopy of a Nb/InAs/Nb superconducting proximity system with a scanning tunneling microscope. PMID- 9998043 TI - Spin disorder in the two-dimensional Hubbard model: A mean-field theory. PMID- 9998044 TI - Influence of the electrodynamic environment on electron tunneling at finite traversal time. PMID- 9998045 TI - Temperature dependence of the Raman scattering in the two-dimensional Heisenberg antiferromagnet. PMID- 9998046 TI - Singlet-pair superconductivity in the two-component anyon gas. PMID- 9998047 TI - Three-site interactions and superconductivity of itinerant spins: A high temperature expansion. PMID- 9998048 TI - Participation of carbon in the electronic structure of YBa2Cu3O7- delta. PMID- 9998049 TI - Flux-pinning potential and its measurement from magnetization decay. PMID- 9998050 TI - Unusual 1/T3 temperature dependence of the Hall conductivity in YBa2Cu3O7- delta. PMID- 9998051 TI - Flux-flow Hall effect in superconducting Tl2Ba2CaCu2O8 films. PMID- 9998052 TI - Shift of x-ray-photoelectron core levels in Bi2Sr2Ca1-xYxCu2Oy: An explanation by bond-valence-sum calculation. PMID- 9998054 TI - Defects, lattice instabilities, and isotope effects in (Y,Pr)Ba-Cu-O high temperature superconductors. PMID- 9998053 TI - Hierarchically occupied pinning distributions and vortex transport in superconductors. PMID- 9998055 TI - Raman spectra of (Bi,Pb)2Sr2CaCu2O8+y single crystals and the role of lead substitution. PMID- 9998056 TI - Flux creep and current relaxation in high-Tc superconductors. PMID- 9998057 TI - Consistency with anomalous electron-phonon interactions of the thermopower of high-Tc superconductors. PMID- 9998059 TI - Magnetic-field-induced strong diamagnetic transition in the quasi-one-dimensional halogen-bridged platinum complex PMID- 9998058 TI - Origin of the anomalous photovoltaic signal in Y-Ba-Cu-O. PMID- 9998060 TI - Evidence of pseudogap formation in a new valence-fluctuating compound: CeRhSb. PMID- 9998061 TI - Quantum diagrams and the prediction of new ternary quasicrystals. PMID- 9998062 TI - Holes in a two-dimensional Hubbard antiferromagnet. PMID- 9998063 TI - Coherence properties of holes subject to a fluctuating spin chirality. PMID- 9998064 TI - Mass enhancement close to a Mott transition. PMID- 9998065 TI - CePdSb: A possible ferromagnetic Kondo-lattice system. PMID- 9998066 TI - Three-state Potts-model spin glasses on hypercubic lattices. PMID- 9998067 TI - Charge-density-wave dynamics in (Ta1-xNbxSe4)2I alloys. PMID- 9998068 TI - Theory of stimulated light scattering in a strongly coupled localized electron phonon system. PMID- 9998069 TI - Multilayer relaxation of a Pb{111} surface. PMID- 9998070 TI - Low-energy electron diffraction and photoemission study of epitaxial films of Cu on Ag{001} PMID- 9998071 TI - Many-body theory of the electronic structures in ultrathin transition-metal films: bcc Co(001). PMID- 9998072 TI - Angle-resolved x-ray photoemission spectroscopy from hcp Co(0001): Forward focusing and atomic imaging. PMID- 9998074 TI - Correlation and multipolar effects in the dielectric response of particulate matter: An iterative mean-field theory. PMID- 9998073 TI - Charge transfer in NixPt1-x alloys studied by x-ray photoelectron spectroscopy. PMID- 9998076 TI - Ground-state properties of lanthanum: Treatment of extended-core states. PMID- 9998075 TI - Pseudopotentials for non-local-density functionals. PMID- 9998077 TI - Structural and magnetic properties of stage-2 CocMn1-cCl2-graphite intercalation compounds. PMID- 9998078 TI - Surface morphology and growth of AgBr on Ag(111). PMID- 9998079 TI - All-electron and pseudopotential force calculations using the linearized augmented-plane-wave method. PMID- 9998080 TI - Magneto-optics of multilayers with arbitrary magnetization directions. PMID- 9998082 TI - Exact scattering theory for the Landauer residual-resistivity dipole. PMID- 9998081 TI - Preparation and thermal stability of metallic glasses Cu83.3-xNixP16.7. PMID- 9998083 TI - Interface effects of hydrogen uptake in Mo/V single-crystal superlattices. PMID- 9998084 TI - Effect of antiphase boundaries on the electronic structure and bonding character of intermetallic systems: NiAl. PMID- 9998085 TI - Effects of the coupling strength of a voltage probe on the conductance coefficients in a three-lead microstructure. PMID- 9998086 TI - Adsorption of positronium on metal surfaces: Theory. PMID- 9998088 TI - Properties of self-interstitials in cubic metals: Static displacements. PMID- 9998087 TI - Local properties in the electronic structure of disordered binary alloys. PMID- 9998089 TI - Spatially resolved Raman studies of diamond films grown by chemical vapor deposition. PMID- 9998090 TI - Calculated elastic constants and structural properties of Mo and MoSi2. PMID- 9998091 TI - Precipitation of gold into metastable gold silicide in silicon. PMID- 9998092 TI - Transient many-body effects in the semiconductor optical Stark effect: A numerical study. PMID- 9998093 TI - Analytical and numerical solutions for a two-dimensional exciton in momentum space. PMID- 9998094 TI - Optical constants of ZnSe in the far infrared. PMID- 9998095 TI - Spin susceptibility and effective mass in shallow doubly doped semiconductor systems. PMID- 9998096 TI - Bulk and surface polaritons in semi-infinite superlattices in a magnetic field: Dispersion relations, optical reflection, and attenuated total reflection. PMID- 9998097 TI - Optically detected magnetic resonance of dislocations in silicon. PMID- 9998098 TI - Molecular-dynamics simulation of thermal conductivity in amorphous silicon. PMID- 9998099 TI - Analytic solutions to the Boltzmann equation for electron transport in silicon. PMID- 9998100 TI - Hydrodynamic theory of intrasubband plasmons in quasi-one-dimensional systems. PMID- 9998101 TI - Infrared analysis of clustering in the II-VI-VI compound CdSexTe1-x. PMID- 9998102 TI - Effects of interface defects on polaron states in GaAs-Ga1-xAlxAs quantum wells. PMID- 9998103 TI - Temperature dependence of the cyclotron-resonance linewidth and effective mass in GaAs/Ga1-xAlxAs square-well structures. PMID- 9998104 TI - Room-temperature growth of Er films on Si(111): A photoelectron spectroscopy investigation. PMID- 9998105 TI - Hydrogen bonding in amorphous silicon with use of the low-pressure chemical-vapor deposition technique. PMID- 9998106 TI - Microscopic theory of second-order Raman scattering in silicon under uniaxial stress. PMID- 9998107 TI - Temperature and interface-roughness dependence of the electron mobility in high mobility Si(100) inversion layers below 4.2 K. PMID- 9998108 TI - High-field transport in semiconductors. II. Collision duration time. PMID- 9998109 TI - High-field transport in semiconductors. III. Wave-function renormalization. PMID- 9998110 TI - Correlation of hot-phonon and hot-carrier kinetics in Ge on a picosecond time scale. PMID- 9998111 TI - Deep-trapping kinematics of charge carriers in amorphous semiconductors: A theoretical and experimental study. PMID- 9998112 TI - Resonant tunneling in amorphous double-barrier structures. PMID- 9998114 TI - Variable-range-hopping magnetoresistance. PMID- 9998113 TI - Far-infrared study of localized states in In-doped Pb0.75Sn0.25Te single crystals. PMID- 9998115 TI - Thermal-annealing studies of defects in lithium fluoride after electron-beam irradiation. PMID- 9998117 TI - Linear and nonlinear optical properties of quartz-type GaPO4. PMID- 9998116 TI - Electron-stimulated desorption of neutral lithium atoms from LiF due to excitation of surface excitons. PMID- 9998118 TI - Molecular-dynamics study of two-dimensional liquid K intercalated in graphite. PMID- 9998119 TI - Structural properties of a three-dimensional all-sp2 phase of carbon. PMID- 9998120 TI - Tip-related electronic artifacts in scanning tunneling spectroscopy. PMID- 9998121 TI - Equilibrium interface width for epitaxial growth with step-height-independent hopping of adatoms. PMID- 9998122 TI - Origin of the shear piezoresistance coefficient pi 44 of n-type silicon. PMID- 9998123 TI - Oxygen chemisorption on cleaved InP(110) surfaces studied with surface differential reflectivity. PMID- 9998124 TI - Absorbing boundary conditions for the finite-difference time-domain calculation of the one-dimensional Schrodinger equation. PMID- 9998125 TI - Nonequilibrium distribution of edge and bulk current in a quantum Hall conductor. PMID- 9998126 TI - Tight-binding study of the electronic structure of amorphous silicon. PMID- 9998128 TI - Erratum: Numerical studies of femtosecond carrier dynamics in GaAs PMID- 9998127 TI - Pressure dependence of the E2 and E1 deep levels in GaAs, GaP, and their alloys. PMID- 9998129 TI - Essential-states mechanism of optical nonlinearity in pi -conjugated polymers. PMID- 9998130 TI - Exchange, spin-orbit, and correlation effects in the soft-x-ray magnetic-circular dichroism spectrum of nickel. PMID- 9998131 TI - Surface phonons and structure of epitaxial nickel layers on Cu(001). PMID- 9998132 TI - Inelastic photoelectron diffraction. PMID- 9998133 TI - Implementation of ultrasoft pseudopotentials in ab initio molecular dynamics. PMID- 9998134 TI - Thermal fluctuations and charge-density-wave depinning in NbSe3: Evidence for phase creep. PMID- 9998135 TI - Collective electronic excitations in small metal clusters. PMID- 9998136 TI - Direct structure determination of oxygen adsorbed on silver by reflection absorption infrared spectroscopy with isotopic substitution. PMID- 9998137 TI - Quenching of collective phenomena in combined intersubband-cyclotron resonances in GaAs. PMID- 9998138 TI - Growth and characterization of epitaxial cubic boron nitride films on silicon. PMID- 9998139 TI - Test of the thermal equilibration model for persistent photoconductivity in doping-modulated amorphous silicon. PMID- 9998140 TI - Semiconductor-surface restoration by valence-mending adsorbates: Application to Si(100):S and Si(100):Se. PMID- 9998141 TI - Experiments on scaling in AlxGa1-xAs/GaAs heterostructures under quantum Hall conditions. PMID- 9998142 TI - Difference phonon scattering: A Raman excitation in GaAs quantum wells. PMID- 9998144 TI - Spin splitting and anomalous Hall resistivity in three-dimensional disordered systems. PMID- 9998143 TI - Polarized-cathodoluminescence study of uniaxial and biaxial stress in GaAs/Si. PMID- 9998145 TI - Relaxation of excitons in coherently strained CdTe/ZnTe quantum wells. PMID- 9998146 TI - Resonances and oscillations in tunneling in a time-dependent potential. PMID- 9998147 TI - Interconfigurational energies in transition-metal atoms using gradient-corrected density-functional theory. PMID- 9998148 TI - Transmission through a Fibonacci chain. PMID- 9998149 TI - Coulomb barriers and adsorbate effects in scanning tunneling microscopy. PMID- 9998150 TI - Multielectron excitations in the K-edge x-ray-absorption near-edge spectra of V, Cr, and Mn 3d0 compounds with tetrahedral coordination. PMID- 9998151 TI - Effect of plasma waves on the optical properties of a multilayered metallic Fibonacci superlattice. PMID- 9998153 TI - Phonons on stepped surfaces. PMID- 9998152 TI - Fine structure of the Ca 2p x-ray-absorption edge for bulk compounds, surfaces, and interfaces. PMID- 9998154 TI - Inelastic scattering from surfaces. PMID- 9998155 TI - Modification of surface states by alkali-metal adsorption and surface reconstruction: An inverse-photoemission study of Na/Ni(110). PMID- 9998156 TI - Hydrogen on rhodium (311): Commensurate adsorption phases, reconstruction, and subsurface binding states. PMID- 9998157 TI - Empirical many-body interatomic potential for bcc transition metals. PMID- 9998158 TI - Theoretical study of the CO interaction with 3d-metal surfaces. PMID- 9998160 TI - Dynamics of self-interstitial atoms in bcc metals. PMID- 9998159 TI - Surface conductance and the diffusion of H and D in Pd. PMID- 9998161 TI - Effect of clustering interactions on the steady-state interface width during epitaxial growth. PMID- 9998163 TI - Anisotropy of the physisorption interaction between H2 and metal surfaces. PMID- 9998162 TI - Fully relativistic calculation of the two-photon momentum distribution for positron annihilation in tungsten. PMID- 9998164 TI - Properties of some low-lying electronic states in polymethineimines and poly(2,3 diazabutadienes). PMID- 9998165 TI - Anomalous mode in the Raman and ir spectra of mercury telluride. PMID- 9998166 TI - Resonant tunneling of holes in the multiband effective-mass approximation. PMID- 9998168 TI - Fermi-level pinning in an Al-Ge metal-semiconductor junction. PMID- 9998167 TI - Electronic structure of short-period n-p GaAs doping superlattices. PMID- 9998169 TI - Influence of bulk-phonon-branch dispersion on displacement patterns and the intermixing of interface and confined optical phonons in superlattices. PMID- 9998170 TI - Effect of intercalated lithium on the electronic band structure of indium selenide. PMID- 9998171 TI - Electronic structure and bonding at SiC/AlN and SiC/BP interfaces. PMID- 9998173 TI - Quasihole lifetimes in electron gases and electron-hole plasmas in semiconductor quantum wells. PMID- 9998172 TI - Transport measurements of resonant-tunneling widths. PMID- 9998174 TI - Magneto-optical properties of the Van Vleck semimagnetic semiconductor Cd1 xFexSe. I. The electronic structure of Fe2+ PMID- 9998176 TI - Quantum theory of plasmons in lateral multiwire superlattices: Intrasubband plasmons and their coupling to intersubband plasmons. PMID- 9998175 TI - Magneto-optical properties of the Van Vleck semimagnetic semiconductor Cd1 xFexSe. II. The bound magnetic polaron. PMID- 9998178 TI - Theoretical study of transport through a quantum point contact. PMID- 9998177 TI - Intraband relaxation time in highly excited semiconductors. PMID- 9998179 TI - Triple excitonic mixing associated with recoupling of a Stark-localized state in coupled quantum wells confined by superlattices. PMID- 9998180 TI - Clustering and reaction for Cr/GaAs(110): Scanning tunneling microscopy and photoemission studies. PMID- 9998181 TI - Structure analysis of Si(111)-( sqrt 3 x sqrt 3 )R30 degrees/Ag using x-ray standing waves. PMID- 9998182 TI - Anisotropy of the picosecond photocurrent in stretched trans-polyacetylene for above- and below-gap excitation. PMID- 9998183 TI - Analysis of the self-energy for an electron gas and a proposal of an improved exchange and correlation potential for band calculations. PMID- 9998184 TI - Negative magnetoresistance in the variable-range-hopping regime in n-type CdSe. PMID- 9998185 TI - Dielectric formalism for a quasi-one-dimensional electron gas. I. Quantum transport equations. PMID- 9998187 TI - Ab initio calculation of phonon dispersions in semiconductors. PMID- 9998186 TI - Dielectric formalism for a quasi-one-dimensional electron gas. II. Dielectric functions and potential correlators. PMID- 9998188 TI - Two-dimensional electronic structure of the GaAs(110)-Bi system. PMID- 9998189 TI - Effect of an applied magnetic field on the charge-density-wave carrier concentration in NbSe3. PMID- 9998191 TI - Electronic structure of cubic and tetragonal zirconia. PMID- 9998190 TI - Soft-x-ray-absorption studies of the electronic-structure changes through the VO2 phase transition. PMID- 9998193 TI - Study of the K band in alkali halides using the pseudopotential method. PMID- 9998192 TI - Quantitative determination of the structural units in phosphorus-selenium glasses by 31P dipolar and magic-angle-spinning NMR spectroscopy. PMID- 9998194 TI - Interior adsorption, channel collimation, and nuclear fusion in solids. PMID- 9998195 TI - Modulational instability and gap solitons in a finite Josephson transmission line. PMID- 9998196 TI - Self-consistent calculation of the collective excitations in neutral and charged jellium microspheres. PMID- 9998197 TI - Multilayer relaxation of clean Ag{001} PMID- 9998198 TI - Formation and structure of misfit dislocations. PMID- 9998199 TI - Pseudoenergies for simulations on metallic systems. PMID- 9998201 TI - Energy spectra of two electrons in a harmonic quantum dot. PMID- 9998200 TI - Submonolayer phases of Pb on Si(111). PMID- 9998202 TI - Periodic conductance fluctuations in quasi-one-dimensional metal-oxide semiconductor field-effect transistors with shallow-trench isolations. PMID- 9998203 TI - Free-carrier absorption in n-type gallium arsenide in quantizing magnetic fields. PMID- 9998204 TI - EL2-defect-related changes in the magnetophotoconductivity of shallow donors in bulk semi-insulating GaAs. PMID- 9998205 TI - Atomic-size effects on the growth of SrF2 and (Ca,Sr)F2 on Si(111). PMID- 9998206 TI - Resonant suppression of the quantized Hall effect in ballistic junctions. PMID- 9998207 TI - Diffraction, phase breaking, and Hall anomalies in quantum dots. PMID- 9998208 TI - Tuning band offsets at semiconductor interfaces by intralayer deposition. PMID- 9998209 TI - Discrete structure of the DX center in GaAs-AlAs superlattices. PMID- 9998210 TI - Fermi-energy-edge singularity in quantum wells containing more than one occupied subband. PMID- 9998211 TI - Tunneling processes between Landau levels and quantum-wire states. PMID- 9998213 TI - Theory of tetragonal twin structures in ferroelectric perovskites with a first order phase transition. PMID- 9998212 TI - Mossbauer studies of iron hydride at high pressure. PMID- 9998214 TI - Orientational ordering in mixed cyanide crystals: (NaCN)1-x(KCN)x. PMID- 9998215 TI - Clustering and percolation of defects in Pr3+:SrF2 using site-selective spectroscopy. PMID- 9998216 TI - Influence of excited-state Pr3+ on the relaxation of the Pr3+:YAlO3 3H4-1D2 transition. PMID- 9998218 TI - Size effects of dislocation stability in nanocrystals. PMID- 9998217 TI - Ferroelectric Sr0.60Ba0.40Nb2O6 thin films by the sol-gel process: Electrical and optical properties. PMID- 9998220 TI - Geometric and dielectric characterization of porous media. PMID- 9998219 TI - Nuclear-spin relaxation in ionically conducting glasses: Application of the diffusion-controlled relaxation model. PMID- 9998221 TI - Surfaces of percolation clusters in three dimensions. PMID- 9998222 TI - Calculation of the temperature-dependent mobility transition for small-polaron hopping in one dimension. PMID- 9998224 TI - Tracer diffusion and thermal stability in amorphous Co-Zr and their relevance for solid-state amorphization. PMID- 9998223 TI - Vibrational densities of states and network rigidity in chalcogenide glasses. PMID- 9998225 TI - Field work and dispersion relations of excitations on fractals. PMID- 9998226 TI - Model-potential study of the lattice dynamics and elastic constants of the Ni0.55Pd0.45 alloy. PMID- 9998227 TI - Exact solution of the t-J model in one dimension at 2t=+/-J: Ground state and excitation spectrum. PMID- 9998229 TI - Possible evidence for an energy gap below the Neel temperature in ternary rare earth compounds. PMID- 9998228 TI - Scaling of critical self-organized magnetic-domain formations. PMID- 9998231 TI - Percolation, clusters, and properties of a dilute Potts model. PMID- 9998230 TI - Electron correlation, d-band formation, and magnetism in V5S8: Photoemission spectroscopy study. PMID- 9998232 TI - Magnetic property of the precursor of polyacenic semiconductive material. PMID- 9998233 TI - Spin dynamics of the concentrated spin glass Y(Mn0.9Al0.1)2. PMID- 9998234 TI - Low-temperature conductivity of dilute alloys in a weak magnetic field. PMID- 9998236 TI - Correlation functions and critical exponents in the one-dimensional anisotropic t J model. PMID- 9998235 TI - Mn1-scrt Crscrt As under pressure: Competition between magnetic orderings. PMID- 9998237 TI - Anisotropy and oxygen-stoichiometry dependence of the dielectric tensor of YBa2Cu3O7- delta (0 <= delta <= 1). PMID- 9998238 TI - Flux quantization in single-crystal YBa2Cu3O7- delta as a function of dc and microwave magnetic fields. PMID- 9998239 TI - Critical current density in iron-doped Y-Ba-Cu-O single crystals. PMID- 9998240 TI - Anomalous shifts of oxygen-mode frequencies in La2-xSrxCuO4, YBa2Cu3O7- delta and Tl2Ba2Ca1-xGdxCu2O8 studied by photoinduced infrared absorption and Raman spectroscopy. PMID- 9998242 TI - Resistive transition, magnetoresistance, and anisotropy in La2-xSrxCuO4 single crystal thin films. PMID- 9998241 TI - High-temperature reverse ac Josephson effect in YBa2Cu3O7. PMID- 9998243 TI - Effect of fluctuations on the transport properties of type-II superconductors in a magnetic field. PMID- 9998244 TI - Topological structures, universality classes, and statistics screening in the anyon superfluid. PMID- 9998245 TI - Spin-1/2 frustrated Heisenberg model at finite temperature. PMID- 9998246 TI - Amplitude of the de Haas-van Alphen oscillations for a marginal Fermi liquid. PMID- 9998247 TI - Effects of gap anisotropy on the electromagnetic response of high-Tc superconductors. PMID- 9998249 TI - Spin polarons in the t-J model. PMID- 9998248 TI - Deviations from the impulse approximation in liquid 4He: Momentum-transfer dependence. PMID- 9998250 TI - Fivefold splitting of the squashing collective mode of superfluid 3He-B by a magnetic field. PMID- 9998251 TI - Spectral weight function in the Hubbard model for a cubic cluster. PMID- 9998252 TI - Order parameters in multisheet superconducting states. PMID- 9998254 TI - Phase diagram of betaine calcium chloride dihydrate in an applied electric field. PMID- 9998253 TI - Flux-flow noise in type-II superconductors. PMID- 9998255 TI - Molecular-dynamics study of elasticity and failure of ideal solids. PMID- 9998257 TI - Testing the phonon spectrum of metallic chromium with the nuclear-resonance photon scattering technique. PMID- 9998256 TI - Length scaling of corner-to-corner propagation on fractal lattices. PMID- 9998259 TI - First-order transition in frustrated quantum antiferromagnets. PMID- 9998258 TI - Critical bifurcation point of the openZ(5)-symmetric spin model. PMID- 9998260 TI - Magnetic ordering in amorphous films of BiFeO3-ZnFe2O4. PMID- 9998261 TI - Anisotropy of the magnetization of Cd1-xFexTe. PMID- 9998262 TI - Self-fields and critical-current-density anisotropy of high-temperature superconductors. PMID- 9998263 TI - Isotropic negative magnetoresistance in La2-xSrxCuO4+y. PMID- 9998264 TI - Proximity effect on the superconducting transition temperature of YBa2Cu3O7 x/PrBa2Cu3O7-x superlattices. PMID- 9998265 TI - Hubbard Hamiltonian for high-Tc superconductors: The antiferromagnetic paramagnetic transition. PMID- 9998267 TI - Comment on "Electron and hole polaron asymmetry in a two-band Peierls-Hubbard material" PMID- 9998266 TI - Discrepancy in the temperature behavior of the modified impulse approximation and the third sum rule. PMID- 9998268 TI - Crossover effects in weakly diluted n >= 2 Ising antiferromagnets. PMID- 9998269 TI - Reply to "Crossover effects in weakly diluted n >= 2 Ising antiferromagnets" PMID- 9998270 TI - Surface melting in a Potts lattice-gas model. PMID- 9998271 TI - Inverse Peierls transition induced by photoexcitation in potassium tetracyanoquinodimethane crystals. PMID- 9998272 TI - Localized ordered structure in polymer latex suspensions as studied by a confocal laser scanning microscope. PMID- 9998273 TI - Crossover in the power spectrum of a driven diffusive lattice-gas model. PMID- 9998274 TI - Frustrated spin-1/2 model in two dimensions with a known ground state. PMID- 9998275 TI - Spin-wave theory for anisotropic Heisenberg antiferromagnets. PMID- 9998277 TI - Crossover from three- to two-dimensional behavior of the vortex energies in layered XY models for high-Tc superconductors. PMID- 9998276 TI - Variational theory of the two-impurity Kondo problem. PMID- 9998278 TI - Long-term nonlogarithmic magnetic relaxation in single-crystal YBa2Cu3O7 superconductors. PMID- 9998279 TI - Interfacial resistive anomaly at a normal-superconducting boundary. PMID- 9998280 TI - Optical mass in the t-J model. PMID- 9998281 TI - Transmission formalism for supercurrent flow in multiprobe superconductor semiconductor-superconductor devices. PMID- 9998282 TI - Energy transfer from noble-gas ions to surfaces: Collisions with carbon, silicon, copper, silver, and gold in the range 100-4000 eV. PMID- 9998283 TI - Luminescence thermal quenching of Cr3+ in zirconium-barium-based fluoride glasses investigated by time-resolved laser spectroscopy. PMID- 9998285 TI - Fractal structure of a cross-linked polymer resin: A small-angle x-ray scattering, pulsed field gradient, and paramagnetic relaxation study. PMID- 9998284 TI - Electronic properties of alpha -quartz under pressure. PMID- 9998286 TI - Scaling functions, self-similarity, and the morphology of phase-separating systems. PMID- 9998287 TI - Dependence of defects induced by excimer laser on intrinsic structural defects in synthetic silica glasses. PMID- 9998288 TI - Nonuniversal critical behavior and first-order transitions in a coupled XY-Ising model. PMID- 9998289 TI - Finite-cluster multiple-scattering theory of x-ray bremsstrahlung isochromat spectra. PMID- 9998291 TI - Line shape and lifetimes of Cr3+ luminescence in silicate glasses. PMID- 9998290 TI - Off-symmetry position of interstitial muons in bismuth. PMID- 9998292 TI - Local structures in the superionic conductor Y3+-doped CeO2 studied using site selective spectroscopy. PMID- 9998294 TI - Computer-simulation studies of extrinsic defects in LiNbO3 crystals. PMID- 9998293 TI - Nonequilibrium shock behavior in quartz. PMID- 9998295 TI - Energy loss of low-energy electrons to nonabrupt metal surfaces. PMID- 9998296 TI - Optimal control of acoustic waves in solids. PMID- 9998297 TI - Effective cluster interactions from cluster-variation formalism. I. PMID- 9998298 TI - Effective cluster interactions from cluster-variation formalism. II. PMID- 9998299 TI - Computation of ring statistics for network models of solids. PMID- 9998300 TI - Theory of second-harmonic generation in strongly scattering media. PMID- 9998301 TI - Scaling theory for the glass transition. PMID- 9998302 TI - Nuclear magnetic relaxation in porous media: The role of the mean lifetime tau ( rho,D). PMID- 9998303 TI - Multiscaling in diffusion-limited aggregation. PMID- 9998304 TI - Nonlinearly coupled vibrational modes and self-trapped states: Quantum Langevin theory and the single-vibron-oscillator case. PMID- 9998305 TI - Molecular-dynamics study of lattice vibrations in the mixed crystal K0.5Rb0.5Cl. PMID- 9998306 TI - Scattering of transverse-magnetic waves with a nonlinear film: Formal field solutions in quadratures. PMID- 9998307 TI - Correlated-squeezed-state approach for phonon coupling in a tunneling system. PMID- 9998308 TI - Resonance-Raman and lattice-dynamics studies of single-crystal PdO. PMID- 9998309 TI - Two-dimensional localized vibrational modes of trans-(CH)x around a soliton. PMID- 9998310 TI - Observation of two-dimensional fractal growth in solids. PMID- 9998311 TI - Resistivity and magnetoresistance of (U1-xMx)Be13 (M=La,Th,Y,Sc,Hf). PMID- 9998312 TI - Magnetic correlations and their dependence on excess oxygen in La2NiO4+ delta. PMID- 9998313 TI - Quantum corrections to the spin-correlation function and the spin-stiffness constant in a two-dimensional Heisenberg antiferromagnet at zero temperature. PMID- 9998314 TI - Magnetic-field distributions at interstitial sites in nondilute alloys. PMID- 9998315 TI - Finite-size effects in thin Ag-Mn spin-glass layers. PMID- 9998316 TI - Critical behavior of the three-dimensional Ising model: A high-resolution Monte Carlo study. PMID- 9998317 TI - Nonlinear magnetization of the one-dimensional S=1 antiferromagnet. PMID- 9998318 TI - Dipole-exchange modes in multilayers with out-of-plane anisotropies. PMID- 9998319 TI - Crystal-field effect for the lanthanide-ion series in metallic copper. PMID- 9998320 TI - Shifts with temperature of the EPR signal in Cu(L-alanine)2: A low-dimensional paramagnet. PMID- 9998321 TI - Evidence of magnetic domains in the reentrant spin glasses Ni1-xMnx studied by neutron depolarization. PMID- 9998322 TI - Row generalization of the fully frustrated triangular XY model. PMID- 9998323 TI - Magnetization and perpendicular anisotropy in Tb/Fe multilayer films. PMID- 9998324 TI - Exact eigenstates of the infinite-range t-J model. PMID- 9998325 TI - Electronic structure and electric-field gradients for YBa2Cu4O8 from density functional calculations. PMID- 9998326 TI - Electron-phonon interactions in the high-temperature superconductors. PMID- 9998327 TI - Hole motion in quantum antiferromagnets: String and hopping results. PMID- 9998328 TI - Comparative study of Cu K-edge x-ray-absorption and Cu 2p x-ray photoelectron spectra in copper oxide compounds. PMID- 9998329 TI - Pairing, condensation, and superconductivity described by a Hubbard model with an attractive interaction. PMID- 9998330 TI - Theory of elasticity of the Abrikosov flux-line lattice for uniaxial superconductors: Parallel flux lines. PMID- 9998331 TI - Dynamics and particle-hole interactions in liquid 3He: A Green's-function approach. PMID- 9998332 TI - Dipolar electric field induced by a vortex moving in an anisotropic superconductor. PMID- 9998333 TI - Infrared optical properties of the 10-K organic superconductor (BEDT-TTF)2 PMID- 9998334 TI - Fractional quantum Hall effect and Chern-Simons gauge theories.